record_id,title,abstract,keywords,authors,year,date,doi,label_included,duplicate_record_id
1,Brain imaging and cognitive predictors of stroke and alzheimer disease in the framingham heart study,"Background and Purpose-Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk. Methods-A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, >55 years; mean, 65.7±7.0) between 1999 and 2004; participants were also free of other neurological conditions that could affect cognition and >90% also had brain MRI examination. We related cognitive and MRI measures to risks of incident stroke and AD ≤10 years of follow-up. As a secondary analysis, we explored these associations in The Framingham Heart Study original cohort (mean age, 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination, respectively). Results-A total of 55 Offspring participants sustained strokes and 31 developed AD. Offspring who scored <1.5 SD below predicted mean scores, for age and education, on an executive function test, had a higher risk of future stroke (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.06-4.85) and AD (HR, 3.60; 95% CI, 1.52-8.52); additional cognitive tests also predicted AD. Participants with low (<20 percentile) total brain volume and high (>20 percentile) white matter hyperintensity volume had a higher risk of stroke (HR, 1.97; 95% CI, 1.03-3.77 and HR, 2.74; 95% CI, 1.51-5.00, respectively) but not AD. Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts (HR, 4.41; 95% CI, 2.00-9.72 and HR, 2.37; 95% CI, 1.12-5.00, respectively). A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers. Conclusions-Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction. © 2013 American Heart Association, Inc.",,"Weinstein, G.;Beiser, A. S.;Decarli, C.;Au, R.;Wolf, P. A.;Seshadri, S.",2013,October,,1,
2,Usefulness of data from magnetic resonance imaging to improve prediction of dementia: population based cohort study,"OBJECTIVE: To determine whether the addition of data derived from magnetic resonance imaging (MRI) of the brain to a model incorporating conventional risk variables improves prediction of dementia over 10 years of follow-up. DESIGN: Population based cohort study of individuals aged >/= 65. SETTING: The Dijon magnetic resonance imaging study cohort from the Three-City Study, France. PARTICIPANTS: 1721 people without dementia who underwent an MRI scan at baseline and with known dementia status over 10 years' follow-up. MAIN OUTCOME MEASURE: Incident dementia (all cause and Alzheimer's disease). RESULTS: During 10 years of follow-up, there were 119 confirmed cases of dementia, 84 of which were Alzheimer's disease. The conventional risk model incorporated age, sex, education, cognition, physical function, lifestyle (smoking, alcohol use), health (cardiovascular disease, diabetes, systolic blood pressure), and the apolipoprotein genotype (C statistic for discrimination performance was 0.77, 95% confidence interval 0.71 to 0.82). No significant differences were observed in the discrimination performance of the conventional risk model compared with models incorporating data from MRI including white matter lesion volume (C statistic 0.77, 95% confidence interval 0.72 to 0.82; P=0.48 for difference of C statistics), brain volume (0.77, 0.72 to 0.82; P=0.60), hippocampal volume (0.79, 0.74 to 0.84; P=0.07), or all three variables combined (0.79, 0.75 to 0.84; P=0.05). Inclusion of hippocampal volume or all three MRI variables combined in the conventional model did, however, lead to significant improvement in reclassification measured by using the integrated discrimination improvement index (P=0.03 and P=0.04) and showed increased net benefit in decision curve analysis. Similar results were observed when the outcome was restricted to Alzheimer's disease. CONCLUSIONS: Data from MRI do not significantly improve discrimination performance in prediction of all cause dementia beyond a model incorporating demographic, cognitive, health, lifestyle, physical function, and genetic data. There were, however, statistical improvements in reclassification, prognostic separation, and some evidence of clinical utility.",Aged;Comorbidity;Dementia/epidemiology/ pathology/physiopathology;Disease Progression;Follow-Up Studies;France;Humans;Magnetic Resonance Imaging;Neuropsychological Tests;Predictive Value of Tests;Prevalence;Prognosis;Prospective Studies;Reproducibility of Results;Risk Factors,"Stephan, B. C.;Tzourio, C.;Auriacombe, S.;Amieva, H.;Dufouil, C.;Alperovitch, A.;Kurth, T.",2015,,,0,
3,Multiple or mixed cerebral microbleeds and dementia in patients with vascular risk factors,"Objective: To investigate whether cerebral microbleeds (CMBs) are independently associated with incident dementia in patients with vascular risk factors. Methods: Using data froma Japanese cohort of participants with vascular risk factors in an observational study from 2001, we evaluated the association between CMBs at baseline and incident dementia. Baseline brain MRI was used to determine small-vessel disease (CMBs, lacunar infarcts, and white matter hyperintensities) and brain atrophy. Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings. Results: Of the 524 subjects (mean age 68±6 8.3 years, 57.6% male, 12.8±6 2.6 years of schooling, 21.6% CMBs), 44 patients with incident dementia (20 Alzheimer disease, 18 vascular dementia, 3 mixed-type, and 3 other) were diagnosed during the median 7.5-year follow-up. In multivariate analysis, the presence of overall CMBs was not associated with an increased risk of incident all-cause dementia (p 5 0.15). However, multiple CMBs (≥2) or mixed (lobar and deep) CMBs were associated with the increased risk of all-cause dementia, whereas strictly lobar CMBs showed no association with any dementia. Conclusions: Multiple CMBs or mixed CMBs independently showed higher risk of all-cause dementia. Our results reinforce the hypothesis that CMBs exert deleterious effects on dementia incidence, suggesting that this association may be mediated by vascular burden.",apolipoprotein E;apolipoprotein e epsilon4;unclassified drug;aged;allele;Alzheimer disease;article;brain atrophy;brain hemorrhage;cerebrovascular disease;clinical article;cognition;controlled study;dementia;disease association;educational status;female;follow up;human;lacunar stroke;male;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;sex;white matter,"Miwa, K.;Tanaka, M.;Okazaki, S.;Yagita, Y.;Sakaguchi, M.;Mochizuki, H.;Kitagawa, K.",2014,,,0,
4,"Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia","OBJECTIVES: Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers. METHODS: Two hundred and twenty-four normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59. 5+/-15.8 years. Mean follow-up is 4.3+/-3.1 years. At follow-up, 22 developed subtle cognitive decline (deltaCCSE>/=-3), 19 became demented, eight with vascular type (VAD) and 11 with Alzheimer's type (DAT) and 183 remain cognitively unchanged. Standardized questionnaires, medical, neuropsychological, neurological and blood work examinations were obtained. Cerebral atrophy, tissue densities and perfusions were measured by xenon-enhanced CT. RESULTS: After age 60, cerebral atrophy, ventricular enlargement, polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis and leuko-araiosis (thinning of grey-white matter densities) were: transient ischaemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5+/-11.9, subtle cognitive decline began, accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension and hyperlipidemia correlated with VAD. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with DAT. CONCLUSION: TIAs, hypertension, hyperlipidemia, smoking and male gender accelerate cerebral degenerative changes, cognitive decline and dementia.","Adult;Aged;Brain/*blood supply/pathology;Cognition Disorders/*etiology/pathology;Cohort Studies;Dementia/*etiology/pathology;Female;Follow-Up Studies;Humans;Hyperlipidemias/complications;Hypertension/complications;Ischemic Attack, Transient/complications;Male;Middle Aged;Neurodegenerative Diseases/epidemiology/*etiology/pathology;Risk Factors;Sex Factors;Smoking/adverse effects;Survival Analysis;Texas/epidemiology","Meyer, J. S.;Rauch, G. M.;Crawford, K.;Rauch, R. A.;Konno, S.;Akiyama, H.;Terayama, Y.;Haque, A.",1999,Dec,,0,
5,Incidence of dementia and associated risk factors in Japan: The Osaki-Tajiri Project,"The incidence of dementia and risk factors has not been fully investigated in Japan. Following a prevalence study in 1998, we investigated the incidence and associated factors in the same population in 2003 and 2005. Randomly selected 771 residents in Tajiri were targeted. The final participants included 204 (65.2%) healthy older adults (Clinical Dementia Rating, CDR 0) and 335 (73.1%) people with questionable dementia (CDR 0.5). We analyzed the incidence of dementia and dementing diseases, and possible risk factors. The risk factors included demographics, lifestyle-related factors, vascular risk factors, cognitive functions, and MRI findings. Overall, 3.9% of the CDR 0 and 37.0% of the CDR 0.5 participants developed dementia during the 5-year period, whereas 40.2% of the CDR 0.5 participants developed dementia during the 7-year period. Older adults had a higher incidence. Higher CDR Box scores had a higher incidence. Of the dementing diseases, 60.8% of participants developed Alzheimer' disease (AD), followed by vascular dementia (VaD), 17.9%. Logistic regression analyses showed that age, MMSE, cognitive functions such as recent memory, and generalized atrophy were significant predictors of progression to AD. Similarly, predictive factors for progression to VaD were age, MMSE, cognitive functions such as frontal function, and white matter lesions and cerebrovascular diseases. A comprehensive system including CDR, cognitive tests, and MRI, is recommended in community-based health policy planning.","Age Distribution;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*epidemiology;Cerebrovascular Disorders/diagnosis/epidemiology;Cognition Disorders/diagnosis/epidemiology;Cohort Studies;Comorbidity;Dementia/diagnosis/*epidemiology;Dementia, Vascular/diagnosis/epidemiology;Demography;Disease Progression;Female;Humans;Incidence;Japan/epidemiology;Life Style;Magnetic Resonance Imaging/statistics & numerical data;Male;Mass Screening;Neuropsychological Tests;Risk Factors","Meguro, K.;Ishii, H.;Kasuya, M.;Akanuma, K.;Meguro, M.;Kasai, M.;Lee, E.;Hashimoto, R.;Yamaguchi, S.;Asada, T.",2007,Sep 15,10.1016/j.jns.2007.04.051,0,
6,"Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old","Objective: To examine the association between brain structural changes and b-amyloid deposition, and incident dementia in 183 elderly subjects without dementia (mean age 85.5 years) 2 years later. Methods: Subjects had a brain structural MRI scan and a PET scan with 11C-labeled Pittsburgh compound B (PiB) in 2009, and were evaluated clinically in 2011. Results: At baseline evaluation, of the 183 participants (146 cognitively normal [CN]); 37 mild cognitive impairment [MCI]), 139 (76%) were PiB1, had small hippocampal volume (,25th percentile), or had high white matter lesion (WML) volume (.75th percentile). Two years later, 111 (61%) were classified as CN, 51 (28%) as MCI, and 21 (11%) as dementia. At baseline, 51% of the CN participants and 67.5% of the MCI cases were PiB1. Thirty percent of the CN and 51% of the MCI cases had small hippocampi, and 24% of the CN and 40.5% of the MCI cases had abnormal WMLs. Of the 21 participants who progressed to dementia, 20 (95%) had at least one imaging abnormality. Only 3 (14%) were only PiB1, 1 (5%) had only small hippocampi, 1 (5%) had only WMLs, 1 (5%) was biomarker negative, and the other 16 had various pairs of imaging abnormalities. Continuous variables of PiB retention, left and right hippocampal volume, and WML volume were independent predictors of dementia in a logistic regression analysis controlling for age, sex, education level, and Mini-Mental State Examination scores. Conclusions: The prevalence of b-amyloid deposition, neurodegeneration (i.e., hippocampal atrophy), and small vessel disease (WMLs) is high in CN older individuals and in MCI. A combination of 2 or 3 of these factors is a powerful predictor of short-term incidence of dementia.",,"Lopez, O. L.;Klunk, W. E.;Mathis, C.;Coleman, R. L.;Price, J.;Becker, J. T.;Aizenstein, H. J.;Snitz, B.;Cohen, A.;Ikonomovic, M.;McDade, E.;Dekosky, S. T.;Weissfeld, L.;Kuller, L. H.",2014,1,,0,
7,"Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community","BACKGROUND New-onset Alzheimer disease (AD) is often attributed to degenerative changes in the hippocampus. However, the contribution of regionally distributed small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging, remains unclear. OBJECTIVE To determine whether regional WMHs and hippocampal volume predict incident AD in an epidemiological study. DESIGN A longitudinal community-based epidemiological study of older adults from northern Manhattan, New York. SETTING The Washington Heights/Inwood Columbia Aging Project. PARTICIPANTS Between 2005 and 2007, 717 participants without dementia received magnetic resonance imaging scans. A mean (SD) of 40.28 (9.77) months later, 503 returned for follow-up clinical examination and 46 met criteria for incident dementia (45 with AD). Regional WMHs and relative hippocampal volumes were derived. Three Cox proportional hazards models were run to predict incident dementia, controlling for relevant variables. The first included all WMH measurements; the second included relative hippocampal volume; and the third combined the 2 measurements. MAIN OUTCOME MEASURE Incident AD. RESULTS White matter hyperintensity volume in the parietal lobe predicted time to incident dementia (hazard ratio [HR] = 1.194; P = .03). Relative hippocampal volume did not predict incident dementia when considered alone (HR = 0.419; P = .77) or with the WMH measures included in the model (HR = 0.302; P = .70). Including hippocampal volume in the model did not notably alter the predictive utility of parietal lobe WMHs (HR = 1.197; P = .049). CONCLUSIONS The findings highlight the regional specificity of the association of WMHs with AD. It is not clear whether parietal WMHs solely represent a marker for cerebrovascular burden or point to distinct injury compared with other regions. Future work should elucidate pathogenic mechanisms linking WMHs and AD pathology.",,"Brickman, A. M.;Provenzano, F. A.;Muraskin, J.;Manly, J. J.;Blum, S.;Apa, Z.;Stern, Y.;Brown, T. R.;Luchsinger, J. A.;Mayeux, R.",2012,Dec,10.1001/archneurol.2012.1527,1,
8,Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study,"BACKGROUND AND PURPOSE: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. METHODS: This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. RESULTS: Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. CONCLUSIONS: White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm.",,"Zuurbier, L. A.;Ikram, M. A.;Luik, A. I.;Hofman, A.;Van Someren, E. J.;Vernooij, M. W.;Tiemeier, H.",2015,Nov,10.1111/ene.12775,0,
9,CADASIL disease diagnosed by molecular DNA test,"CADASIL disease (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) was described in 1991 by Tournier-Lasserve. Two years later the same authors described its association with chromosome 19; nonetheless, the mutations in gene Notch3 were not described until 1996. Clinical findings depend on the age at onset. The early form of the illness is found in young patients, generally less than 30 years old, and the main clinical manifestation is a migraine headache with subcortical lesions in the white matter, while in the later form ischemic events and behavioral symptoms are predominant. Anatomo-pathological findings in CADASIL include the presence of osmophilic granular deposits in vessel walls, skin, muscles and cerebral arteries. We present a patient with CADASIL and cavernous angioma. We studied a 40-year-old woman who underwent surgery for a left temporal-parietal cavernous angioma, with aphasia as the only symptom, two years before admission. Her family history showed that her father had suffered from vascular dementia. She was admitted to our hospital with right-side hemiparesis and dysarthria. A CT scan showed the presence of ischemic vascular lesions and former surgery sequelae. The duplex scan of the neck vessels and a transesophageal echocardiogram ruled out an embolic source. Laboratory tests including VDRL, HIV, prothrombotic profile and rheumatologic screening tests were normal. An MRI in T2W and FLAIR showed the presence of multiple subcortical cerebral lesions and hyperintensity in the white matter (leukoencephalopaty). We found a left acute putaminal-capsular infarct in the diffusion-MRI. The MRA was normal. Analysis of the cerebrospinal fluid was unremarkable. A molecular DNA test was performed, and a nucleotide substitution in position 583 in exon 4 of gene Notch3 was detected. This mutation was found only in CADASIL patients. The association with cavernous angioma has not been previously reported, and we believe that it was unrelated to CADASIL, either clinically or genetically. To our knowledge, this is the first case of CADASIL diagnosed by molecular DNA test in our country.",acetylsalicylic acid;antithrombocytic agent;dipyridamole;DNA;Notch receptor;nucleotide;adult;article;autosomal dominant disorder;behavior disorder;brain embolism;brain ischemia;brain scintiscanning;CADASIL;case report;cavernous hemangioma;chromosome 19;clinical feature;comorbidity;computer assisted tomography;controlled study;DNA determination;dysarthria;exon;female;gene mutation;genetic linkage;headache;hemiparesis;histopathology;human;intravascular ultrasound;leukoencephalopathy;migraine;multiinfarct dementia;nuclear magnetic resonance imaging;nucleic acid base substitution;onset age;screening test;syndrome;transesophageal echocardiography;white matter;aspirin,"Zurru, M. C.;Casas Parera, I.;Moya, G.;Giovanelli, C.;Genovese, O.;Gatto, E.",2002,,,0,
10,High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion,"Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology.","Animals;Behavior, Animal/physiology;Brain/ blood supply/diagnostic imaging/pathology;Carotid Artery, Common/physiopathology;Carotid Stenosis/complications/diagnostic imaging/ physiopathology;Cerebrovascular Circulation/ physiology;Cognition Disorders/ etiology/physiopathology/psychology;Diabetes Mellitus, Experimental/complications/diagnostic imaging/ physiopathology;Diet, High-Fat/ adverse effects;Endothelium, Vascular/physiopathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Maze Learning/physiology;Mice, Inbred C57BL;Vascular cognitive impairment;cerebral blood flow;chronic cerebral hypoperfusion;cognitive impairment;diabetes;high-fat diet;vascular dementia","Zuloaga, K. L.;Johnson, L. A.;Roese, N. E.;Marzulla, T.;Zhang, W.;Nie, X.;Alkayed, F. N.;Hong, C.;Grafe, M. R.;Pike, M. M.;Raber, J.;Alkayed, N. J.",2016,Jul,,0,11
11,High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion,"Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology.",,"Zuloaga, K. L.;Johnson, L. A.;Roese, N. E.;Marzulla, T.;Zhang, W.;Nie, X.;Alkayed, F. N.;Hong, C.;Grafe, M. R.;Pike, M. M.;Raber, J.;Alkayed, N. J.",2015,Nov 11,10.1177/0271678x15616400,0,
12,Brain imaging abnormalities in mental disorders of late life,"Psychiatric inpatients with dementia (N = 61) or depression (N = 67) in late life were 2.6 times more likely to manifest magnetic resonance imaging abnormalities of the brain than were elderly controls (N = 44). Controlling for the effects of age and gender, demented patients were distinguishable from controls by an increased prevalence of cortical atrophy and infarction, while depressed patients exhibited an increased prevalence of cortical infarctions and leukoencephalopathy. Patients with dementia were distinguishable from those with major depression by an increased prevalence of cortical atrophy. These results indicate that major depression in late life, like dementia, is associated with a remarkable increase in overt pathologic changes in the brain.","Adolescent;Adult;Age Factors;Aged;Aged, 80 and over;Brain/ pathology/radiography;Dementia/ diagnosis/radiography;Depression/ diagnosis/radiography;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Reference Values;Regression Analysis;Sex Factors;Tomography, X-Ray Computed","Zubenko, G. S.;Sullivan, P.;Nelson, J. P.;Belle, S. H.;Huff, F. J.;Wolf, G. L.",1990,Oct,,0,
13,N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population,"Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter. Conclusion In community-dwelling persons, higher serum NT-proBNP levels are associated with volumetric and microstructural MR imaging markers of subclinical brain damage. (c) RSNA, 2016 Online supplemental material is available for this article.",,"Zonneveld, H. I.;Ikram, M. A.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Krestin, G. P.;Franco, O. H.;Vernooij, M. W.",2017,Apr,,0,
14,Prevalence of cortical superficial siderosis in a memory clinic population,"Objective: To determine prevalence, topography, and severity of cortical superficial siderosis (SS), a recently recognized manifestation of cerebral amyloid angiopathy, and its possible association with Alzheimer disease (AD) in a memory clinic patient cohort. Methods: We included 809 patients (56% men, aged 66 6 10 years) from the Amsterdam Dementia Cohort between November 2010 and November 2012 scanned on a 3-tesla MRI system. We analyzed prevalence and topography of cortical SS according to demographic, clinical, and MRI data. Agreement for SS detection between 2 neuroradiologists was calculated by using Cohen k. Results: Agreement for detection of SS was excellent (unweighted k of 0.81). In 17 patients (2.1%), cortical SS was found without a known cause. The prevalence of idiopathic SS differed according to diagnostic groups (p , 0.001): nearly 5% (95% confidence interval [CI] 2.8%- 8.2%) in patients with AD (n 5 168) vs 2% (95%CI 0.7%-6.0%) in patients with mild cognitive impairment (n 5 143) and 2.5% (95% CI 0.7%-8.7%) in other types of dementia (n 5 80). By contrast, SS was not found in patients with subjective complaints (n 5 168) or in those with other disorders (n5157). Presence of SS was associated with APOE e4, microbleeds, and white matter hyperintensities (all p , 0.05) independent of diagnosis. Conclusion: The prevalence of cortical SS in a memory clinic setting is higher than reported in the general population but lower than reported in cerebral amyloid angiopathy. The relatively high prevalence of SS in AD suggests that SS is a relevant radiologic manifestation of amyloid pathology in AD. Presence of SS does not seem to predict severity of AD. Further longitudinal research is needed to investigate clinical relevance.",adult;aged;Alzheimer disease;article;clinical trial;cohort analysis;cortical superficial siderosis;cross-sectional study;demography;disease association;disease severity;female;human;major clinical study;male;middle aged;nuclear magnetic resonance imaging;prevalence;priority journal;siderosis;topography;vascular amyloidosis,"Zonneveld, H. I.;Goos, J. D. C.;Wattjes, M. P.;Prins, N. D.;Scheltens, P.;Van Der Flier, W. M.;Kuijer, J. P. A.;Muller, M.;Barkhof, F.",2014,,,0,
15,Early-onset dementia with prolonged occipital seizures: An atypical case of Kufs disease,"Objective: Kufs disease is the adult-onset form of neuronal ceroid lipofuscinosis (NCL). Its two clinical phenotypes are type A (progressive myoclonus epilepsy with dementia) and type B (behavioral abnormalities and dementia, associated with pyramidal and extrapyramidal signs). Methods: We describe the clinical evolution of an atypical case characterized by progressive dementia and focal occipital seizures. Results: A healthy 37-year-old woman began showing memory deficits and behavioral disturbances (apathy, lack of inhibitions, untidiness). After 4 years, she developed rare clusters of tonic-clonic seizures, as well as focal seizures originating from the temporo-occipital regions, clinically associated with visual hallucinations, wandering, and agitation. When she was 44 years old, neuropsychological assessment revealed severe frontotemporal dementia. MRI showed cortical atrophy and, on T2-weighted images, hypointensity of the basal ganglia, and hyperintensity and reduction of the deep white matter. On the basis of these findings, a diagnosis of Kufs disease was hypothesized. A skin biopsy was negative, but electron microscopy examination of a right frontal lobe brain biopsy revealed the presence of typical storage material (fingerprint inclusions). The patient never developed myoclonus or extrapyramidal signs. Discussion: Kufs disease is difficult to diagnose on account of its heterogeneous clinical pattern and pathologic features, and the lack of a specific genetic locus alteration. The neuropsychological pattern and MRI findings observed in patients with early-onset frontotemporal dementia and seizure disorder suggest that Kufs disease should be considered in their differential diagnosis. Extracerebral biopsy can be nondiagnostic, and when alternative diagnoses have been ruled out, cerebral biopsy should be considered. © 2008 by AAN Enterprises, Inc.",,"Zini, A.;Cenacchi, G.;Nichelli, P.;Zunarelli, E.;Todeschini, A.;Meletti, S.",2008,18,,0,
16,"Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region","The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/metabolism;Amnesia/ diagnosis/metabolism;Diagnosis, Differential;Diffusion Tensor Imaging/ methods;Female;Gyrus Cinguli/metabolism/ pathology;Humans;Magnetic Resonance Spectroscopy/ methods;Male;Middle Aged;Perfusion Imaging/ methods","Zimny, A.;Szewczyk, P.;Trypka, E.;Wojtynska, R.;Noga, L.;Leszek, J.;Sasiadek, M.",2011,,10.3233/jad-2011-110254,0,
17,Quantitative evaluation of changes in the selected white matter tracts using diffusion tensor imaging in patients with Alzheimer's disease and mild cognitive impairment,"This study evaluated the damage to the extensive range of white matter tracts in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Thirty-four patients with AD (mean age 71.5 yrs, MMSE 17.6), 23 patients with MCI (mean age 66 yrs, MMSE 27.4) and 15 normal controls (mean age 69 yrs, MMSE 29.8) were enrolled. Diffusion tensor imaging (DTI) was performed in 25 directions on 1.5 T MR scanner. Fractional anisotropy (FA) values were obtained with a small ROI method in several association tracts including posterior cingulum fibers, in commissural tracts (genu and splenium of corpus callosum) and projection tracts (middle cerebellar peduncles and posterior limbs of internal capsules). In MCI significant reductions of FA were found in the inferior longitudinal fascicles, left superior longitudinal fascicle and posterior cingulum fibers compared to normal controls. In AD significantly decreased FA values were detected in the same fascicles as in MCI and additionally in inferior fronto-occipital tracts and commissural tracts. In both AD and MCI the most severe changes were found within posterior cingulum fibers. No abnormalities were detected in projection tracts in both groups. Accuracy of DTI in detecting AD and MCI reached 0.95 and 0.79, respectively. FA measurements strongly correlated with neuropsychological tests. DTI is capable of depicting microstructural changes within white matter fiber tracts in dementia and may aid the differential diagnosis of AD and MCI.",,"Zimny, A.;Szewczyk, P.;Bladowska, J.;Trypka, E.;Wojtynska, R.;Leszek, J.;Sasiadek, M.",2012,Jul,,0,
18,Does perfusion CT enable differentiating Alzheimer's disease from vascular dementia and mixed dementia? A preliminary report,"The purpose of the study was to evaluate the usefulness of perfusion CT (pCT) in differentiating Alzheimer's disease (AD) from vascular dementia (VaD) and mixed dementia (MixD). pCT was performed in 41 patients (mean age, 68.3 years): 24 with AD, 8 with VaD, and 9 with MixD. Regional perfusion parameters (rCBF, rCBV, and rMTT) were calculated from 31 ROIs in the grey and white matter of the frontal and temporal lobes, basal ganglia, and internal capsules bilaterally. The obtained data for the subgroups of AD, VaD, and MixD patients were compared statistically. CONCLUSIONS: On the basis of rCBF and rCBV values, pCT may be a valuable method of distinguishing between AD and VaD but it seems to be of little significance in differentiating MixD from VaD and of no usefulness in distinguishing between AD and MixD.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/physiopathology/*radiography;Basal Ganglia/pathology/physiopathology/radiography;Brain/pathology/physiopathology/*radiography;Cerebral Arteries/pathology/physiopathology;Cerebrovascular Circulation/physiology;Contrast Media/standards;Dementia, Vascular/pathology/physiopathology/*radiography;Diagnosis, Differential;Female;Frontal Lobe/pathology/physiopathology/radiography;Humans;Internal Capsule/pathology/physiopathology/radiography;Iodine Radioisotopes;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests;Temporal Lobe/pathology/physiopathology/radiography;Tomography, X-Ray Computed/*methods/standards","Zimny, A.;Sasiadek, M.;Leszek, J.;Czarnecka, A.;Trypka, E.;Kiejna, A.",2007,Jun 15,10.1016/j.jns.2007.01.051,0,
19,Analysis of correlation between the degree of cognitive impairment and the results of perfusion CT in patients with dementia,"BACKGROUND: The aim of the study was to assess the relationship between cognitive impairment according to the Mini Mental State Examination (MMSE) and values of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) obtained in perfusion CT (pCT). MATERIAL/METHODS: Sixty-four patients with dementia (36 with Alzheimer's disease, 15 with vascular dementia, and 13 with mixed dementia), aged 45-92 years (mean: 69.9 years) with different degrees of cognitive impairment (mean MMSE score: 17.0) were involved in the study. All subjects underwent pCT at the level of the basal ganglia (50 scans, 1 scan/s, 40 ml contrast medium at 4 ml/s, delay: 7 s). CBF, CBV, and MTT values from 31 regions of interest (ROIs) in the gray and white matter of the frontal and temporal lobes, lentiform nuclei, and internal capsules were correlated with the MMSE scores. RESULTS: Statistical analysis of CBF and MMSE revealed significant correlations in 22/31 ROIs including the gray and white matter of the frontal and temporal lobes, both internal capsules, right and left hemispheres, and total gray and white matter. Analysis of CBV and MMSE showed significant correlations in 21/31 ROIs in the gray and white matter of the frontal and temporal lobes, both internal capsules, left lentiform nucleus, right and left hemispheres, as well as total gray matter. There were no significant correlations between MTT and MMSE. CONCLUSIONS: CBF and CBV calculated with pCT correlate with cognitive impairment in patients with dementia and thus may play a role in monitoring disease progression or therapeutic response.","Aged;Aged, 80 and over;Brain/anatomy & histology/pathology/physiology;Cerebrovascular Circulation/*physiology;Cognition Disorders/*pathology/*physiopathology/radiography;Dementia/*pathology/*physiopathology/radiography;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Regional Blood Flow;Statistics as Topic;Tomography, X-Ray Computed","Zimny, A.;Leszek, J.;Kiejna, A.;Sasiadek, M.",2007,May,,0,
20,Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's disease, whereas its role in vascular cognitive impairment (VCI) is largely unknown. In this study, we investigated the impact of CR in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247 NOTCH3 mutation carriers from a two-center study were investigated using detailed neuropsychological and neuroimaging protocols. CR was operationalized as years of formal education. Brain pathology was assessed by MRI using normalized brain volume and lacunar lesion volume as proxies. Multivariate analyses were done for each structural measure with scores of processing speed, executive function, and memory as dependent variables. Additional linear regression models were conducted with interaction terms for education x brain volume and education x lacunar lesion volume. Education had an independent impact on cognitive performance in subjects with mild and moderate degrees of brain pathology, whereas there was no significant influence of education on cognition in patients with severe MRI changes. This interaction was found for processing speed, the cognitive domain most impaired in our patients. Our findings demonstrate an interaction of education and brain pathology in regard to cognitive impairment: the effect of education seems most pronounced in early disease stages but may ultimately be overwhelmed by the pathological changes. The results extend the concept of CR to VCI.",Adult;Aged;Brain/*pathology/physiopathology;CADASIL/*pathology/physiopathology/psychology;Cognition;*Cognitive Reserve;Educational Status;Executive Function;Female;Humans;Magnetic Resonance Imaging;Male;Memory;Middle Aged;Neuropsychological Tests;Prospective Studies,"Zieren, N.;Duering, M.;Peters, N.;Reyes, S.;Jouvent, E.;Herve, D.;Gschwendtner, A.;Mewald, Y.;Opherk, C.;Chabriat, H.;Dichgans, M.",2013,Feb,10.1016/j.neurobiolaging.2012.04.019,0,
21,Mapping track density changes in nigrostriatal and extranigral pathways in Parkinson's disease,"In Parkinson's disease (PD) the demonstration of neuropathological disturbances in nigrostriatal and extranigral brain pathways using magnetic resonance imaging remains a challenge. Here, we applied a novel diffusion-weighted imaging approach-track density imaging (TDI). Twenty-seven non-demented Parkinson's patients (mean disease duration: 5 years, mean score on the Hoehn & Yahr scale=1.5) were compared with 26 elderly controls matched for age, sex, and education level. Track density images were created by sampling each subject's spatially normalized fiber tracks in 1mm isotropic intervals and counting the fibers that passed through each voxel. Whole-brain voxel-based analysis was performed and significance was assessed with permutation testing. Statistically significant increases in track density were found in the Parkinson's patients, relative to controls. Clusters were distributed in disease-relevant areas including motor, cognitive, and limbic networks. From the lower medulla to the diencephalon and striatum, clusters encompassed the known location of the locus coeruleus and pedunculopontine nucleus in the pons, and from the substantia nigra up to medial aspects of the posterior putamen, bilaterally. The results identified in brainstem and nigrostriatal pathways show a large overlap with the known distribution of neuropathological changes in non-demented PD patients. Our results also support an early involvement of limbic and cognitive networks in Parkinson's disease.","Aged;Brain Stem/pathology;Cognition;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Limbic System/pathology;Male;Middle Aged;Neostriatum/ pathology;Neural Pathways/ pathology;Neuropsychological Tests;Parkinson Disease/ pathology/psychology;Substantia Nigra/ pathology","Ziegler, E.;Rouillard, M.;Andre, E.;Coolen, T.;Stender, J.;Balteau, E.;Phillips, C.;Garraux, G.",2014,Oct 1,10.1016/j.neuroimage.2014.06.033,0,
22,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia,"INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middle-aged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors--diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. CONCLUSION: Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.",,"Zidverc-Trajković, J.;Lacković, V.;Pavlović, A.;Bajcetić, M.;Carević, Z.;Tomić, G.;Mandić, G.;Mijajlović, M.;Jovanović, Z.;Sternić, N.",2008,2008,,0,
23,Cognitive impairments associated with periventricular white matter hyperintensities are mediated by cortical atrophy,"BACKGROUND: Previous studies have shown that white matter lesions (WMLs) is an important risk factor for cognitive impairment, but the underlying mechanisms have not been clarified. OBJECTIVE: We tested the hypothesis that the cognitive impairments associated with periventricular white matter hyperintensities (PWMHs) on magnetic resonance imaging (MRI) would be mediated by the cortical thinning of corresponding area. METHOD: Sixteen stroke- and dementia-free subjects with PWMHs and 16 healthy control subjects were enrolled in this study. All participants underwent an examination of cognition, MRI-based cortical thickness measurement and a MRI-DTI scan. Then, the possible relationships among cognitive impairments, PWMHs and the topography of cortical thinning were analyzed. RESULTS: Comparing with the controls, the cognitive tests of the subjects with PWMHs showed significant decline in the domains of verbal fluency and executive function. After accounting for age, gender, years of education, and treatable vascular risk factors related to cognitive performance, cortical thickness had an independent influence on the cognitive impairments, especially in the frontal pole, orbitofrontal cortex, superior and middle frontal gyrus, superior and middle temporal gyrus, insula, and cuneus. CONCLUSIONS: Our results suggest that the association between PWMHs and cognitive impairments is mediated by cortical thinning.","Aged;Atrophy/pathology;Cerebral Cortex/ pathology;Cognition Disorders/ pathology;Diffusion Tensor Imaging;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology","Zi, W.;Duan, D.;Zheng, J.",2014,Sep,10.1111/ane.12262,0,
24,White matter integrity in mild cognitive impairment: a tract-based spatial statistics study,"Mild cognitive impairment (MCI) as a clinical diagnosis has limited specificity, and identifying imaging biomarkers may improve its predictive validity as a pre-dementia syndrome. This study used diffusion tensor imaging (DTI) to detect white matter (WM) structural alterations in MCI and its subtypes, and aimed to examine if DTI can serve as a potential imaging marker of MCI. We studied 96 amnestic MCI (aMCI), 69 non-amnestic MCI (naMCI), and 252 cognitively normal (CN) controls. DTI was performed to measure fractional anisotropy (FA), and tract-based spatial statistics (TBSS) were applied to investigate the characteristics of WM changes in aMCI and naMCI. The diagnostic utility of DTI in distinguishing MCI from CN was further evaluated by using a binary logistic regression model. We found that FA was significantly reduced in aMCI and naMCI when compared with CN. For aMCI subjects, decreased FA was seen in the frontal, temporal, parietal, and occipital WM, together with several commissural, association, and projection fibres. The best discrimination between aMCI and controls was achieved by combining FA measures of the splenium of corpus callosum and crus of fornix, with accuracy of 74.8% (sensitivity 71.0%, specificity 76.2%). For naMCI subjects, WM abnormality was more anatomically widespread, but the temporal lobe WM was relatively spared. These results suggest that aMCI is best characterized by pathology consistent with early Alzheimer's disease, whereas underlying pathology in naMCI is more heterogeneous, and DTI analysis of white matter structural integrity can serve as a potential biomarker of MCI and its subtypes.","Aged;Aged, 80 and over;Cognition Disorders/ pathology;Computer Simulation;Data Interpretation, Statistical;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Models, Anatomic;Models, Statistical;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Zhuang, L.;Wen, W.;Zhu, W.;Trollor, J.;Kochan, N.;Crawford, J.;Reppermund, S.;Brodaty, H.;Sachdev, P.",2010,Oct 15,10.1016/j.neuroimage.2010.05.068,0,
25,"Microstructural white matter changes, not hippocampal atrophy, detect early amnestic mild cognitive impairment","BACKGROUND: Alzheimer's disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. METHODS: We studied 155 cognitively normal (CN) and 27 'late' aMCI individuals with stable diagnosis over 2 years, and 39 'early' aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts. RESULTS: Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes. CONCLUSIONS: Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.","Aged;Aged, 80 and over;Amnesia/ complications;Atrophy/pathology/physiopathology;Brain/ pathology/physiopathology;Diffusion Tensor Imaging;Female;Hippocampus/pathology/physiopathology;Humans;Imaging, Three-Dimensional;Male;Memory, Episodic;Mild Cognitive Impairment/ complications/ pathology/physiopathology;Organ Size;Time Factors","Zhuang, L.;Sachdev, P. S.;Trollor, J. N.;Reppermund, S.;Kochan, N. A.;Brodaty, H.;Wen, W.",2013,,10.1371/journal.pone.0058887,0,
26,Microstructural white matter changes in cognitively normal individuals at risk of amnestic MCI,"Objective: Since Alzheimer disease (AD) is a slowly progressive disorder and its pathologic features are likely to be present for many years before symptoms become manifest, we investigated whether microstructural white matter changes similar to those identified in patients with AD can be detected in cognitively normal individuals without dementia destined to develop amnestic mild cognitive impairment (aMCI). Methods: We studied 193 cognitively normal individuals, of whom 173 remained cognitively stable (CN-stable) and 20 were diagnosed with aMCI (CN-aMCI converter) 2 years later. Structural MRI and diffusion tensor imaging were acquired at baseline to assess gray matter atrophy and microstructural white matter changes, respectively. Results: At baseline, compared with CN-stable, CN-aMCI converters had substantial reductions in white matter integrity in the precuneus, parahippocampal cingulum, parahippocampal gyrus white matter, and fornix. Other diffuse white matter changes were observed in the frontal, parietal, and subcortical regions, whereas gray matter structures were relatively intact. The fractional anisotropy (FA) values of the precuneus were found to be a predictor of conversion from cognitively normal to aMCI. In addition, the FA values of the left parahippocampal gyrus white matter were predictive of subsequent episodic memory decline. Conclusions: Microstructural white matter changes are present in cognitively normal individuals in the pre-aMCI stage, and may serve as a potential imaging marker of early AD-related brain changes. Copyright © 2012 by AAN Enterprises, Inc.",,"Zhuang, L.;Sachdev, P. S.;Trollor, J. N.;Kochan, N. A.;Reppermund, S.;Brodaty, H.;Wen, W.",2012,21,,0,
27,"Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: A population-based study","BACKGROUND AND PURPOSE: Little is known about the risk factors of dilated Virchow-Robin spaces (dVRS) and their relation with other markers of brain small vessel disease. We investigated both issues in a large population-based sample of elderly individuals. METHODS: Severity of dVRS was semiquantitatively graded in both white matter and basal ganglia using high-resolution 3-dimensional MRI images taken from 1818 stroke- and dementia-free subjects enrolled in the Three-City Dijon MRI study. Multinomial logistic regression models were used to model the association of cardiovascular risk factors, APOE genotype, brain atrophy, and MRI markers of small vessel disease with the degree of dVRS. RESULTS: Severity of dVRS was found to be strongly associated with age in both basal ganglia (degree 4 versus 1: OR, 2.1; 95% CI, 1.4 to 3.2) and white matter (OR, 1.5; 95% CI, 1.2 to 1.9). The proportion of hypertensive subjects increased with the degrees of dVRS in both basal ganglia (P=0.02) and white matter (P=0.048). Men presented a higher risk of severe dVRS in basal ganglia than women, particularly degree 4 (OR, 6.0; 95% CI, 1.8 to 19.8). The degree of dVRS was associated with the volume of white matter hyperintensities and the prevalence of lacunes, but not with brain atrophy. CONCLUSION: In this large cohort study of elderly subjects, the degree of dVRS appears independently associated with age, hypertension, volume of white matter hyperintensities, and lacunar infarctions. dVRS should be considered as another MRI marker of cerebral small vessel disease in the elderly with regional variations in their severity.",marker;nuclear magnetic resonance imaging;population;blood pressure;white matter;basal ganglion;aged;brain atrophy;model;risk factor;brain;cerebrovascular accident;dementia;logistic regression analysis;genotype;risk;female;prevalence;cohort analysis;cardiovascular risk;hypertension;infarction;city,"Zhu, Y. C.;Tzourio, C.;Soumaré, A.;Mazoyer, B.;Dufouil, C.;Chabriat, H.",2010,,10.1161/strokeaha.110.591586,0,28
28,"Severity of dilated virchow-robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: A population-based study","Background and Purpose: Little is known about the risk factors of dilated Virchow-Robin spaces (dVRS) and their relation with other markers of brain small vessel disease. We investigated both issues in a large population-based sample of elderly individuals. Methods: Severity of dVRS was semiquantitatively graded in both white matter and basal ganglia using high-resolution 3-dimensional MRI images taken from 1818 stroke-and dementia-free subjects enrolled in the Three-City Dijon MRI study. Multinomial logistic regression models were used to model the association of cardiovascular risk factors, APOE genotype, brain atrophy, and MRI markers of small vessel disease with the degree of dVRS. Results: Severity of dVRS was found to be strongly associated with age in both basal ganglia (degree 4 versus 1: OR, 2.1; 95% CI, 1.4 to 3.2) and white matter (OR, 1.5; 95% CI, 1.2 to 1.9). The proportion of hypertensive subjects increased with the degrees of dVRS in both basal ganglia (P=0.02) and white matter (P=0.048). Men presented a higher risk of severe dVRS in basal ganglia than women, particularly degree 4 (OR, 6.0; 95% CI, 1.8 to 19.8). The degree of dVRS was associated with the volume of white matter hyperintensities and the prevalence of lacunes, but not with brain atrophy. CONCLUSION-: In this large cohort study of elderly subjects, the degree of dVRS appears independently associated with age, hypertension, volume of white matter hyperintensities, and lacunar infarctions. dVRS should be considered as another MRI marker of cerebral small vessel disease in the elderly with regional variations in their severity. © 2010 American Heart Association, Inc.",,"Zhu, Y. C.;Tzourio, C.;Soumaré, A.;Mazoyer, B.;Dufouil, C.;Chabriat, H.",2010,November,,0,
29,High degree of dilated virchow-robin spaces on MRI is associated with increased risk of dementia,"The clinical significance of dilated Virchow-Robin spaces (dVRS) remains unclear and their impact on cognitive performances has only been reported in small sample studies. Our aim was to assess the association between severity of dVRS and risk of incident dementia and cognitive decline in an elderly cohort. The degree of dVRS in both white matter and basal ganglia were ranked using high-resolution 3D MRI in a population-based sample of 1,778 non-demented participants from 65 to 80 years of age, who had a cerebral MRI at baseline. Cognitive function was assessed and dementia was diagnosed during a 4-year follow-up period. Cox proportional hazard models were used to examine the association between dVRS degree on a four-level severity score and incident dementia. The relationship between dVRS degree and change in cognition was examined using linear mixed effect models. During 6,135 person-years of follow-up, 27 individuals developed dementia. The highest degree of dVRS was associated with a strong increase in the risk of incident dementia independently of other standard risk factors of dementia, both for dVRS in white matter (HR=9.8, 95% CI 1.7-55.3) and in basal ganglia (HR =5.8, 95% CI 1.2-28.4). After further adjustment on white matter hyperintensity volume and brain infarcts, this association remained significant for dVRS in white matter. Higher rate of cognitive decline was found to be related to high degree of dVRS in basal ganglia but not in white matter. These results need confirmation but they suggest that assessment of the severity of dVRS may help identify groups of individuals that are at increased risk of dementia. © 2010 - IOS Press and the authors. All rights reserved.",aged;article;basal ganglion;brain infarction;clinical assessment;cognition;cognitive defect;correlation analysis;dementia;diagnostic accuracy;diagnostic test accuracy study;diagnostic value;dilated virchow robin space;disease association;disease course;female;human;major clinical study;male;nuclear magnetic resonance imaging;predictive validity;priority journal;risk factor;white matter,"Zhu, Y. C.;Dufouil, C.;Soumaré, A.;Mazoyer, B.;Chabriat, H.;Tzourio, C.",2010,,,0,
30,[Identification of a novel NOTCH3 mutation in a family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy],"OBJECTIVE: To analyze potential mutations of NOTCH3 gene in a Chinese family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in order to facilitate genetic counseling and prenatal diagnosis. METHODS: The proband and related family members and 100 healthy controls were recruited. The NOTCH3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing. PolyPhen-2 and SIFT software were used to predict the protein function. RESULTS: The proband and two affected individuals from the family were adult-onset, with main clinical manifestations including recurrent transient ischemic attacks and(or) strokes, cognitive impairment, memory decline, and depression. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A novel heterozygous missense mutation c.3043T> A (p.Cys1015Ser) located in exon 19 of NOTCH3 gene was identified not only in the proband and two patients, but also in an asymptomatic relative from the family. The same mutation was detected in none of the 100 unrelated healthy controls. Function analysis suggested that this mutation can severely affect the functions of this protein. Multiple sequence alignment revealed that the mutation site was extremely conserved in various species. CONCLUSION: A novel heterozygous Cys1015Ser mutations in exon 19 of the NOTCH3 gene probably underlies the CADASIL in this family.","Adult;Aged;Amino Acid Sequence;Base Sequence;CADASIL/complications/*genetics;DNA Mutational Analysis;Exons/*genetics;Family Health;Female;Heterozygote;Humans;Male;Middle Aged;Molecular Sequence Data;*Mutation, Missense;Pedigree;Polymerase Chain Reaction;Receptors, Notch/*genetics;Sequence Homology, Amino Acid","Zhu, Y.;Wang, J.;Wu, Y.;Wang, G.;Hu, B.;Xu, A.",2014,Oct,10.3760/cma.j.issn.1003-9406.2014.01.008,0,
31,Effect of six-month standardized tertiary rehabilitation program on the activities of daily living in stroke patients with hemiplegia,"Background: At present, there are many studies on the rehabilitation therapy of stroke patients with hemiplegia, but there is deficiency of corresponding standardized rehabilitation program. Objective: To explore the effects of standardized tertiary rehabilitation on the activities of daily living in stroke patients with hemiplegia within 6 months after attack. Design: A clinical observation. Setting: Department of Rehabilitation Medicine, Huashan Hospital of Fudan University. Participants: Eighty-two outpatients and inpatients with acute stroke were selected from the Department of Neurology, Shanghai Huashan Hospital from January 1999 to June 2003, including 49 males and 33 females, 40 - 80 years of age, with a mean age of (65±11) years old. Inclusive criteria: According to the diagnostic standards for cerebrovascular diseases set by Fourth National Academic Meeting for Cerebrovascular Disease in 1995, the patients were diagnosed as new attack of cerebral infarction or cerebral hemorrhage, and confirmed by CT or MRI to be initial patients; They should be accorded with the following conditions, including within 1 week after stabilization of life signs, Glasgow coma score > 8 points, 40 - 80 years of age, with disturbance of limb function. Informed consents were obtained from all the patients or their relatives. Exclusive criteria: Patients were excluded due to active liver disease, liver and kidney malfunction, congestive heart failure, malignant tumor, history of dementia, failure in respiratory function, tetraplegia; cerebral infarction or cerebral hemorrhage for more than 3 weeks; unable to be followed up due to in other cities and provinces; psychiatric history; deafness and muteness. According to the will of the patients or their relatives, the patients who accepted the standardized rehabilitation program were enrolled as the treatment group (n =42), and the others as the control group (n =40). Approval was obtained from the ethical committee of the hospital. Methods: All the patients were given routine therapies of internal medicine after admission. According to the conditions of Brunnstom recovery 6-phase evaluation, the patients in the treatment group were trained with the pre-designed comprehensive standardized rehabilitation program for corresponding period. At early period (within about 1 month after attack), the patients received rehabilitative interventions in the Department of Emergency or Department of Neurology, once a day, 45 minutes for each time, 5 times a week; At middle period (about 1 - 3 months after attack), the patients received rehabilitative interventions in the rehabilitation ward or center, once to twice a day, 30 - 45 minutes for each time, 4 - 5 days a week; At late period (about 3 - 6 months after attack), the patients received rehabilitative intervention mainly assisted by rehabilitation physician in the community, relatives and volunteers, 3 - 4 times a week, and they were followed in the house or outpatient department once every two weeks. Main outcome measures: The patients were evaluated blindly by the same rehabilitation physician using scale of modified Barthel index at admission and 1, 3 and 6 months after attack respectively. Results: Totally 82 patients with acute stroke were enrolled, and 3 cases in the treatment group missed, including 2 cases died at 1 month after admission, and 1 case refused the follow up 10 days later, all the others were involved in the analysis of results. The scores of modified Barthel index at corresponding time points after admission in the treatment group were all obviously higher than those in the control group (P < 0.01), and the score differences were also obviously higher than those in the control group (P < 0.01). The activities of daily living at admission and 1, 3 and 6 months after admission in the treatment group were 22.50%, 46.43%, 75.95% and 89.52% of that of normal people respectively, and those in the control group were 17.09%, 25.77%, 43.38% and 55.00% respectively. The activities of daily living at admission and 1, 3 and 6 month in the treatment group were 131.66%, 180.17%, 175.08% and 162.76% of those in the control group. As compared with at admission, the percentage of the score difference to the total score at the ends of the 1st, 3rd and 6th months were 23.93%, 53.45% and 67.02% in the treatment group, while 8.67%, 25.36% and 36.98% in the control group. Conclusion: Standardized tertiary rehabilitation can obviously promote the activities of daily living in stroke patients with hemiplegia.",adult;aged;article;Barthel index;brain hemorrhage;brain infarction;cerebrovascular disease;clinical observation;computer assisted tomography;controlled study;daily life activity;disease duration;female;functional disease;Glasgow coma scale;hemiplegia;hospital patient;human;informed consent;major clinical study;male;nuclear magnetic resonance imaging;occupational therapy;outpatient;physiotherapy;rehabilitation care;stroke patient;treatment outcome,"Zhu, Y.;Hu, Y.;Wu, Y.;Jiang, C.;Fan, W.;Sun, L.;Xie, Z.;Shen, L.;Zhu, B.;Bai, Y.",2007,,,0,
32,Serum Hepatocyte Growth Factor Is Associated with Small Vessel Disease in Alzheimer's Dementia,"Background: While hepatocyte growth factor (HGF) is known to exert cell growth, migration and morphogenic effects in various organs, recent studies suggest that HGF may also play a role in synaptic maintenance and cerebrovascular integrity. Although increased levels of HGF have been reported in brain and cerebrospinal fluid (CSF) samples of patients with Alzheimer's disease (AD), it is unclear whether peripheral HGF may be associated with cerebrovascular disease (CeVD) and dementia. In this study, we examined the association of baseline serum HGF with neuroimaging markers of CeVD in a cohort of pre-dementia (cognitive impaired no dementia, CIND) and AD patients. Methods: Serum samples from aged, Non-cognitively impaired (NCI) controls, CIND and AD subjects were measured for HGF levels. CeVD (cortical infarcts, microinfarcts, lacunes, white matter hyperintensities (WMH) and microbleeds) were assessed by magnetic resonance imaging (MRI). Results: After controlling for covariates, higher levels of HGF were associated with both CIND and AD. Among the different CeVD MRI markers in CIND and AD, only small vessel disease, but not large vessel disease markers were associated with higher HGF levels. Conclusion: Serum HGF may be a useful peripheral biomarker for small vessel disease in subjects with cognitive impairment and AD.",Alzheimer's disease;CeVD;cognitive impaired no dementia;hepatocyte growth factor;small vessel disease,"Zhu, Y.;Hilal, S.;Chai, Y. L.;Ikram, M. K.;Venketasubramanian, N.;Chen, C. P.;Lai, M. K. P.",2018,,,0,
33,Serum IL-8 is a marker of white-matter hyperintensities in patients with Alzheimer's disease,"INTRODUCTION: Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer's disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD. METHODS: We performed a cross-sectional case-control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)-6, IL-8, and tumor necrosis factor alpha levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white-matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging. RESULTS: After controlling for covariates, higher concentrations of IL-8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5-13.4 and AD with CeVD: OR 7.26; 95% CI 1.2-43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL-8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4-5.6). DISCUSSION: Serum IL-8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow-up studies would help validate these findings.",Alzheimer's disease;Cerebrovascular disease;Cognitive impairment;Dementia;Il-8;Inflammation;White-matter hyperintensities,"Zhu, Y.;Chai, Y. L.;Hilal, S.;Ikram, M. K.;Venketasubramanian, N.;Wong, B. S.;Chen, C. P.;Lai, M. K.",2017,,,0,
34,Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-Inositol using magnetic resonance spectroscopic imaging,"Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD. Copyright © 2006 by Lippincott Williams & Wilkins.",,"Zhu, X.;Schuff, N.;Kornak, J.;Soher, B.;Yaffe, K.;Kramer, J. H.;Ezekiel, F.;Miller, B. L.;Jagust, W. J.;Weiner, M. W.",2006,April/May/June,,0,
35,Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease,"PURPOSE: Brain iron deposition has been proposed to play an important role in the pathophysiology of neurodegenerative diseases. The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with Alzheimer disease (AD). MATERIALS AND METHODS: This study was approved by the institutional review board of Tongji Hospital (Wuhan, China) and written informed consent was obtained from all participants. Fifteen patients with AD, 15 age-and sex-matched healthy controls, and 30 healthy volunteers underwent high-resolution magnetic resonance (MR) phase-corrected imaging. The phase shift and iron concentrations of the bilateral hippocampus (HP), parietal cortex (PC), frontal white matter, putamen (PU), caudate nucleus (CN), thalamus, red nucleus, substantia nigra, and dentate nucleus (DN) of the cerebellum were examined for correlation with severity of dementia by using a two-tailed Student-Newman-Keuls t test (analysis of variance) and linear correlation test. RESULTS: Regional phase shifts on phase-corrected images were negatively correlated with regional brain iron concentration in healthy adults (r = -0.926, P = .003). Iron concentrations in the bilateral HP, PC, PU, CN, and DN subregions of patients with AD were significantly higher than the controls (P < .05), Moreover, these brain iron concentrations, especially those in the PC at the early stages of AD, were positively correlated with the severity of patients' cognitive impairment (P < .05). CONCLUSION: Iron concentration in the PC was positively correlated with the severity of AD patients' cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/psychology;Biomarkers/analysis;Brain/ metabolism;Cognition;Female;Humans;Iron/ metabolism;Magnetic Resonance Imaging/methods;Male;Middle Aged","Zhu, W. Z.;Zhong, W. D.;Wang, W.;Zhan, C. J.;Wang, C. Y.;Qi, J. P.;Wang, J. Z.;Lei, T.",2009,Nov,10.1148/radiol.2532082324,0,
36,Patterns of white matter injury in HIV infection after partial immune reconstitution: a DTI tract-based spatial statistics study,"HIV-infected individuals with severe immune suppression are more likely to develop HIV-associated neurocognitive disorders than those with preserved immune function. While partial immune reconstitution occurs in those with severe immune suppression after starting combined antiretroviral therapy, it is not established whether improvement in immune function reverses or prevents injury to the central nervous system (CNS). To address this question, 50 participants (nadir CD4 counts </= 200 cells/mm(3), on a stable antiretroviral regimen for at least 12 consecutive weeks prior to study) and 13 HIV negative participants underwent a comprehensive neurological evaluation followed by diffusion tensor imaging (DTI). Eighty-four percent of the 50 HIV participants were neurologically asymptomatic (HIVNA) and 16 % had mild cognitive impairment (HIVCI). Tract-based spatial statistics (TBSS) on DTI data revealed that mean diffusivity (MD) increased significantly in the posterior aspect of both hemispheres in HIVNA compared to controls. In HIVCI, compared to controls and HIVNA, increased MD extended to prefrontal areas. Fractional anisotropy decreased only in HIVCI, compared to either controls or HIVNA. Furthermore, DTI showed significant correlations to duration of HIV infection and significant associations with multiple cognitive domains. This study highlights that in partial immune reconstitution, injury to the CNS is present even in those that are neurologically asymptomatic and there are discrete spatial patterns of white matter injury in HIVNA subjects compared to HIVCI subjects. Our results also show that quantitative analysis of DTI using TBSS is a sensitive approach to evaluate HIV-associated white matter disease and thus valuable in monitoring central nervous system injury.","AIDS Dementia Complex/ immunology/ pathology;Anti-Retroviral Agents/therapeutic use;Brain/pathology;Diffusion Magnetic Resonance Imaging;Female;HIV Infections/drug therapy/ immunology/ pathology;Humans;Image Interpretation, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests","Zhu, T.;Zhong, J.;Hu, R.;Tivarus, M.;Ekholm, S.;Harezlak, J.;Ombao, H.;Navia, B.;Cohen, R.;Schifitto, G.",2013,Feb,10.1007/s13365-012-0135-9,0,
37,The association between small vessel infarcts and the activities of amyloid-beta peptide degrading proteases in apolipoprotein E4 allele carriers,"Small vessel (SV) and large vessel (LV) brain infarcts are distinct pathologies. Using a homebound elderly sample, the numbers of either infarct subtypes were similar between those apolipoprotein E4 allele (ApoE4) carriers (n = 80) and noncarriers (n = 243). We found that the higher the number of SV infarcts, but not LV infarcts, a participant had, the higher the activity of substrate V degradation in serum especially among ApoE4 carriers (beta = +0.154, SE = 0.031, P < .0001) after adjusting for the confounders. Since substrate V degradation could be mediated by insulin-degrading enzyme (IDE) or/and angiotensin-converting enzyme (ACE), but no relationship was found between SV infarcts and specific ACE activities, blood IDE may be a useful biomarker to distinguish the brain infarct subtypes. Insulin-degrading enzyme in blood may also imply an important biomarker and a pathological event in Alzheimer disease through SV infarcts in the presence of ApoE4.","Aged;Aged, 80 and over;Alleles;Amyloid beta-Peptides/*metabolism;Apolipoprotein E4/*genetics;Biomarkers/metabolism;Brain Infarction/diagnosis/*enzymology/genetics;Cross-Sectional Studies;Dementia/diagnosis;Female;Heterozygote;Humans;Insulysin/physiology;Magnetic Resonance Imaging;Male;Peptide Hydrolases/metabolism;apolipoprotein E4 allele;small vessel brain infarct;substrate V degradation","Zhu, H.;Bhadelia, R. A.;Liu, Z.;Vu, L.;Li, H.;Scott, T.;Bergethon, P.;Mwamburi, M.;Rosenzweig, J. L.;Rosenberg, I.;Qiu, W. Q.",2013,Nov,10.1177/0003319712462125,0,
38,Alzheimer's disease and amnestic mild cognitive impairment weaken connections within the default-mode network: A multi-modal imaging study,"We applied a multi-modal imaging approach to examine structural and functional alterations in the default-mode network (DMN) that are associated with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), a transitional phase between healthy cognitive aging and dementia. Subjects included 10 patients with probable AD, 11 patients with aMCI, and 12 age- and education-matched normal controls (NC). Whole-brain resting-state functional, diffusion-weighted, and volumetric magnetic resonance imaging (MRI) data as well as (18)F-fluorodeoxyglucose-based positron emission tomography (FDG-PET) data were acquired. We carried out resting-state functional MRI-based functional connectivity and diffusion MRI-based structural connectivity analyses using isthmus of the cingulate cortex (ICC) and the subjacent white matter as the seeds. Whole-brain group and region of interest-based analyses demonstrated that AD weakens the structural and functional connections between ICC and other regions within the DMN, consistent with regional reduction of metabolic activity and atrophy within the DMN. A progressive weakening trend of these connections was also observed from NC to aMCI and then AD, although significant differences between aMCI and the other two groups were not found. Overall, based on both FDG-PET and MRI results, the DMN appears to serve as a window to understanding structural and functional brain changes associated with AD and aMCI. © 2013 - IOS Press and the authors. All rights reserved.",,"Zhu, D. C.;Majumdar, S.;Korolev, I. O.;Berger, K. L.;Bozoki, A. C.",2013,2013,,0,
39,White matter lesion load is associated with resting state functional MRI activity and amyloid PET but not FDG in mild cognitive impairment and early Alzheimer's disease patients,"PURPOSE: To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. MATERIALS AND METHODS: Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [(18)F]-Florbetapir tracer and metabolism of glucose by means of [(18)F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). RESULTS: Whole-brain WMLL and amyloid deposition were significantly higher (P < 0.005) in MCI and AD patients compared with controls. RS-fMRI results showed significantly reduced (corrected P < 0.05) DMN connectivity and altered fALFF activity in both MCI and AD groups. FDG uptake results showed hypometabolism in AD and MCI patients compared with controls. Correlations (P < 0.05) were found between WMLL and amyloid load, FDG uptake and amyloid load, as well as between amyloid load (rSUV) and fALFF. CONCLUSION: Our quantitative results of four MRI and PET imaging metrics (fALFF/DMN, WMLL, amyloid, and FDG rSUV values) agree with published values. Significant correlations between MRI metrics, including WMLL/functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD.","Aged;Alzheimer Disease/ diagnosis;Brain/pathology/radionuclide imaging;Female;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/ diagnosis;Plaque, Amyloid/ radionuclide imaging;Positron-Emission Tomography/ methods;Radiopharmaceuticals;Rest;White Matter/ pathology","Zhou, Y.;Yu, F.;Duong, T. Q.",2015,Jan,10.1002/jmri.24550,0,
40,A primary study of diffusion tensor imaging-based histogram analysis in vascular cognitive impairment with no dementia,"PURPOSE: This study performed diffusion tensor imaging (DTI) histogram analysis and voxel-based analysis (VBA) to detect white matter (WM) damage in patients with vascular cognitive impairment with no dementia (VCIND) and to determine correlations between DTI histogram-derived measures and cognitive dysfunction in these patients. MATERIALS AND METHODS: Among patients with subcortical ischemic vascular disease, 18 patients with VCIND were selected along with 18 age- and sex-matched cognitive-normal subjects. Both groups underwent magnetic resonance and DTI scans, and fractional anisotropy (FA) changes in VBA between the two groups were assessed. Further, mean diffusivity (MD) and FA histograms of WM and normal-appearing WM (NAWM) in each subject were evaluated. RESULTS: Compared to control, the VCIND group showed lower FA values throughout the brain. FA and MD histogram patterns of WM and NAWM were significantly different between the groups. Significant differences were found in all DTI histogram-derived measures, except in the mean FA peak height of WM and mean MD peak location of NAWM. Neuropsychological results (z-scores) were found to be significantly correlated with mean FA peak location, average MD, mean MD peak location of WM, and mean FA peak height, average MD, mean MD peak location of NAWM. CONCLUSIONS: Results of VBA and diffusion tensor imaging-based histogram analysis suggest that VCIND patients have more severe damage in WM and NAWM than the control. Thus, the severity of damage in WM and NAWM may be related with cognitive dysfunction in VCIND patients, and DTI histogram analysis can help in further understanding VCIND.","Adult;Aged;Anisotropy;Brain/pathology;Brain Ischemia/pathology;Cerebral Cortex/pathology;Cerebrovascular Disorders/ pathology;Cognition/physiology;Cognition Disorders/ pathology;Data Interpretation, Statistical;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Ischemic Attack, Transient/pathology;Male;Middle Aged;Neuropsychological Tests;Stroke/pathology","Zhou, Y.;Qun, X.;Qin, L. D.;Qian, L. J.;Cao, W. W.;Xu, J. R.",2011,Feb,10.1016/j.clineuro.2010.09.007,0,
41,Serum antioxidant levels associated with subcortical ischemic vascular disease,"OBJECTIVE: We aimed to examine changes in serum bilirubin and uric acid (ua) levels in subcortical ischemic vascular disease (Sivd). in addition, we investigated if altered serum bilirubin and ua levels correlate with the subtypes of Sivd as well as the severity of leukoaraiosis (la). METHODS: this cross-sectional study included 1098 consecutive patients with slight symptoms, such as dizziness, vertigo etc. according to magnetic resonance imaging (Mri) appearances, they were divided into either Sivd group or controls (Cn), and the Sivd group was further grouped in lacunar infarction (li) and la subtypes, as well as different grades. Serum bilirubin and ua levels were determined by the vanadate oxidase method and enzymatic method respectively, after at least an eight hour overnight fasting, in all subjects. RESULTS: the bilirubin level was obviously lower while the ua level was significantly higher in the Sivd group when compared with the controls. Moreover, the la subgroup presented more significant changes in bilirubin and ua when compared to the li subgroup in both males and females. the correlation was positive between the ua levels and the la severity (r=0.134, p=0.006). Multivariate regression analysis revealed that the odds ratio (95% Ci) for Sivd in the lowest tertile of total bilirubin (tbil<9.58 mumol/l) and highest tertile of ua (ua>339 mumol/l) were 2.702(1.936-3.770) and 2.135(1.521-2.996) respectively after adjusting for confounding variables. CONCLUSION: Serum bilirubin levels were lower, whereas ua levels were higher in Sivd patients when compared with controls in both males and females, especially in la patients. Moreover, serum ua levels positively correlated to la severity.","Aged;Antioxidants/*metabolism;Bilirubin/*blood;Biomarkers/blood;Brain Ischemia/*blood/diagnosis;Cross-Sectional Studies;Dementia, Vascular/*blood/diagnosis;Female;Humans;Male;Middle Aged;Uric Acid/*blood","Zhou, X.;Wang, L.;Liu, H.;Zhang, C.;Zhu, M.;Zhu, X.;Hao, J.;Sun, Z.",2014,May,,0,
42,Type of symptomatology of cognitive impairment in patients with acute ischemic stroke,"Objective To investigate the type of symptomatology of cognitive impairment in patients with acute ischemic stroke. Methods A total of 208 consecutive patients with acute ischemic stroke admitted to the Department of Neurology, the First Affiliated Hospital of Zhejiang University (ra = 155) and the Department of Neurology, Jiaxing Second Hospital (n =53) from November 2013 to November 2014 were collected prospectively. The cognitive function was assessed by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating Scale (CDRS). Cognitive impairment was diagnosed according to the diagnostic criteria of vascular dementia and vascular mild cognitive impairment from National Institute for Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) and the American Heart Association/American Stroke Association (AHA/ASA). Mean while,on the basis of score weight of each cognitive domain on the ADAS-cog, the symptom typing was conduced. The baseline characteristics, imaging, and neurological deficits of each type were compared. Results The patients with acute ischemic stroke were divided into 5 types according the characteristics of cognitive impairment:normal type 61 patients (29.3%). memory impairment predominated type 10 (4.8%) .language impairment predominated type 35 (16. 8%) .operating impairment predominated type 14 (6. 7%). and complex type 88 (42. 3%). There were significant differences in age.years of education, and sex of patients in each type (all P < 0. 05) .while there were no significant differences among the histories of diabetes. hypertension, hyperlipidemia and stroke (all P >0. 05). There were no significant differences in the imaging infarct location and the number of infarction in each type (all P >0. 05). There were no significant differences in the comparison of the modified Ranking scale (MRS) scores and the National Institute of Health Stroke Scale (NIHSS) scores on admission in each type (all P >0.05). Conclusions Most of the patients with acute ischemic stroke have cognitive impairment. According to the symptomatology, vascular cognitive impairment can be divided into 5 types. This typing reflects the heterogeneity of vascular cognitive impairment; however, there are no significant differences in imaging and neurological deficit performance in each type.",Alzheimer's Disease Assessment Scale cognitive subscale;article;brain ischemia;cerebrovascular accident;Clinical Dementia Rating;cognition;cognitive defect;dementia assessment;diabetes mellitus;human;hyperlipidemia;hypertension;language disability;major clinical study;medical society;memory disorder;Mini Mental State Examination;multiinfarct dementia;National Institutes of Health Stroke Scale;neuroimaging;symptomatology,"Zhou, P.;Yuan, H.;Ji, R.;Ruan, J.;Wei, G.;Shen, H.;Zhou, Q.;Luo, B.",2016,,,0,
43,Hierarchical anatomical brain networks for MCI prediction: Revisiting volumetric measures,"Owning to its clinical accessibility, T1-weighted MRI (Magnetic Resonance Imaging) has been extensively studied in the past decades for prediction of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The volumes of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) are the most commonly used measurements, resulting in many successful applications. It has been widely observed that disease-induced structural changes may not occur at isolated spots, but in several inter-related regions. Therefore, for better characterization of brain pathology, we propose in this paper a means to extract inter-regional correlation based features from local volumetric measurements. Specifically, our approach involves constructing an anatomical brain network for each subject, with each node representing a Region of Interest (ROI) and each edge representing Pearson correlation of tissue volumetric measurements between ROI pairs. As second order volumetric measurements, network features are more descriptive but also more sensitive to noise. To overcome this limitation, a hierarchy of ROIs is used to suppress noise at different scales. Pairwise interactions are considered not only for ROIs with the same scale in the same layer of the hierarchy, but also for ROIs across different scales in different layers. To address the high dimensionality problem resulting from the large number of network features, a supervised dimensionality reduction method is further employed to embed a selected subset of features into a low dimensional feature space, while at the same time preserving discriminative information. We demonstrate with experimental results the efficacy of this embedding strategy in comparison with some other commonly used approaches. In addition, although the proposed method can be easily generalized to incorporate other metrics of regional similarities, the benefits of using Pearson correlation in our application are reinforced by the experimental results. Without requiring new sources of information, our proposed approach improves the accuracy of MCI prediction from 80.83% (of conventional volumetric features) to 84.35% (of hierarchical network features), evaluated using data sets randomly drawn from the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset. © 2011 Zhou et al.",,"Zhou, L.;Wang, Y.;Li, Y.;Yap, P. T.;Shen, D.;Alzheimer's Disease Neuroimaging, I.",2011,,,0,
44,Modeling disease progression via multi-task learning,"Alzheimer's disease (AD), the most common type of dementia, is a severe neurodegenerative disorder. Identifying biomarkers that can track the progress of the disease has recently received increasing attentions in AD research. An accurate prediction of disease progression would facilitate optimal decision-making for clinicians and patients. A definitive diagnosis of AD requires autopsy confirmation, thus many clinical/cognitive measures including Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) have been designed to evaluate the cognitive status of the patients and used as important criteria for clinical diagnosis of probable AD. In this paper, we consider the problem of predicting disease progression measured by the cognitive scores and selecting biomarkers predictive of the progression. Specifically, we formulate the prediction problem as a multi-task regression problem by considering the prediction at each time point as a task and propose two novel multi-task learning formulations. We have performed extensive experiments using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Specifically, we use the baseline MRI features to predict MMSE/ADAS-Cog scores in the next 4. years. Results demonstrate the effectiveness of the proposed multi-task learning formulations for disease progression in comparison with single-task learning algorithms including ridge regression and Lasso. We also perform longitudinal stability selection to identify and analyze the temporal patterns of biomarkers in disease progression. We observe that cortical thickness average of left middle temporal, cortical thickness average of left and right Entorhinal, and white matter volume of left Hippocampus play significant roles in predicting ADAS-Cog at all time points. We also observe that several MRI biomarkers provide significant information for predicting MMSE scores for the first 2. years, however very few are shown to be significant in predicting MMSE score at later stages. The lack of predictable MRI biomarkers in later stages may contribute to the lower prediction performance of MMSE than that of ADAS-Cog in our study and other related studies. © 2013 Elsevier Inc.",algorithm;Alzheimer disease;Alzheimer's Disease Assessment Scale cognitive subscale;article;brain size;cognition;controlled study;cortical thickness (brain);disease course;disease marker;disease model;entorhinal cortex;hippocampus;intermethod comparison;longitudinal study;mental performance;mental task;mild cognitive impairment;Mini Mental State Examination;nuclear magnetic resonance imaging;prediction;priority journal;rating scale;scoring system;single task learning algorithm;temporal cortex;white matter,"Zhou, J.;Liu, J.;Narayan, V. A.;Ye, J.",2013,,,0,
45,Cerebral white matter lesions and cognitive function in a non-demented Chinese veteran cohort,"This study examined the association between cerebral white matter lesions (WMLs) and cognitive function in a male, non-demented Chinese veteran cohort. A total of 662 participants underwent CT scan and cognitive function assessments; 51 were excluded from the analysis because they exhibited non-lacunar infarcts or suspected dementia. Subjects were allocated to one of four groups according to WML status and between-group comparisons were made for seven cognitive function tests. Logistic regression was used to assess odds ratios for impaired performance associated with WML status. In all cognitive tests, subjects with severe WMLs differed significantly from those without WMLs or with mild WMLs, and in three tests subjects with severe WMLs differed significantly from those with moderate WMLs. For each cognitive test severe WMLs were strongly associated with increased risk of impaired performance. Severe WMLs were associated with greater diminished cognitive function and there may be a WML threshold after which, in elderly Chinese subjects, an impact on cognitive function occurs.",Aged;Brain/*pathology;Brain Diseases/*diagnosis/psychology;Cerebral Ventricles/pathology;China;Cognition Disorders/*diagnosis/psychology;Humans;Male;Memory;Neuropsychological Tests;Odds Ratio;Veterans,"Zhou, G.;Ren, S.;Chen, N.;Duan, L.;Zhang, Z.;Fang, S.;Zhao, W.",2008,Jan-Feb,,0,
46,Correlation between the occurrence of vascular dementia and the stroke-position after first attack of stroke,"Aim: To explore the relationship between the occurrence of vascular dementia (VD) and the stroke-position in patients with first stroke. Methods: All patients including 269 patients with cerebral infarction (CI) and 94 patients with cerebral hemorrhage (CH) were examined with the mini-mental state examination (MMSE) at admission, and they were followed up for 3 months after stroke. The stroke-positions were diagnosed by using cranial CT or MRI. Results: Three months after stroke, there were no significant differences in the occurrence rates of VD between the CI group (17.8%, 48/269) and CH group (19.2%, 18/94) (X2 = 0.082, P > 0.05). The results of Logistic analysis of stroke-position in patients with or without dementia after stroke indicated that, for the patients with CI, infarction in thalamencephalon was the most important influencing factor for VD, and followed by infarction accompanied with the subcortical leukoencephalopathy, temporal lobe, multiple lacunar infarction in order; and for the CI patients, thalamic hemorrhage had the most important effect on VD, followed by the hemorrhage of temporal lobe. Conclusion: VD commonly occurs in the patients with first stroke, and the occurrence of post-stroke. VD is closely related with the stroke position.",adult;aged;article;brain hemorrhage;brain infarction;brain scintiscanning;computer assisted tomography;correlation analysis;female;follow up;hospital admission;human;leukoencephalopathy;major clinical study;male;mesencephalon;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;risk factor;cerebrovascular accident;temporal lobe;thalamus,"Zhong, W. Z.;Lin, X. J.;Ning, J. L.;Liang, H.;Li, L. L.",2004,,,0,
47,Quantitative evaluation of regional cerebral blood flow in patients with silent Leukoaraiosis,"Aim: To detect the cerebral blood flow (CBF) of patients with silent Leukoaraiosis to observe the changes of their cerebral circulation and cerebral function. Methods: The mean CBF and regional CBF were quantita tively detected with (99m)Tc-ECD and consecutive single photon emission computerized tomography (SPECT) in 20 patients with silent Leukoaraiosis and 15 normal elderly people. The patients with silent Leukoaraiosis were the outpatients or inpatients of the Department of Neurology, the First Affiliated Hospital of Dalian Medical University between August 2001 and January 2003, and the normal elderly people were the elderly healthy physical examinees in this hospital. At 30 minutes before SPECT, all the subjects orally took potassium perchlorate (200-400 mg) to reduce the uptake of developer by choroids plexus, salivary gland and thyroid gland, in order to avoid affecting the quality of image. The developer was infused via elbow vein in a pellet manner, and dynamic collection was performed immediately. Spot sources were placed at external ear hole and lateral canthus to statically collected cerebral parenchyma for 30 s, so as to define the orbitomeatal (OM) line, and collected with SPECT. The image reconstruction was applied to the original data, and the SPECT image was treated with Lassen correction after the mean CBF was obtained, and then the quantitative image was collected. We selected three transaxial slices above the OM line at 50 mm, 60 mm and 70 mm, respectively, and 20 regions of interest (ROIs) were set symmetrically in different bagal ganglia and different cortex to quantitatively detect the regional CBF. Cognitive function was assessed with mini-mental state examination (MMSE), and the total score was 30 points, < 24 was considered as dementia. Results: All the 20 patients with silent Leukoa raiosis and 15 normal elderly people finished the examination and entered the analysis of results. (1 The mean CBF, and the regional CBF of frontal, temporal and parietal lobe cortexes and loose area of cerebral white matter in the silent Leukoaraiosis group were all obviously decreased as compared with those in the control group [(369.1±41.6), (394.2±36.5) mL/g per minute, t=2.30, P < 0.05; (308.6±28.7), (340.8±36.2) mL/g per minute, t=2.56, P < 0.05; (384.9±50.1), (409.8±37.5) mL/g per minute, t=2.23, P < 0.05; (414.1 ±50.7), (443.8±52.3) mL/g per minute, t=2.31, P < 0.05; (283.4±33.8), (312.5±34.3) mL/g per minute, t=2.49, P < 0.05], and the decrease of frontal lobe cortex was more significant. 2 The mean CBF was insignificantly different among the patients with mild, moderate and severe silent Leukoaraiosis [(375.2±17.1), (368.5±32.9), (353.6±47.7) mL/g per minute, F=2.46, P > 0.05]. 3 Of the 20 patients with silent Leukoaraiosis, the score of MMSE did not reach the degree of dementia, but only 2 cases had total score, and the other 18 cases all had decreases of calculation and memory to different extent, and showed mild cerebral hypofunction. Conclusion: Extensive cerebral blood flow perfusion exists in the brain of patients with silent Leukoaraiosis, which was involved in the loose area of cerebral white matter, and frontal, temporal and parietal lobe cortexes, and the patients have cerebral hypofunction. The measurement of CBF by SPECT can be used as an effective way to monitor the progression of diseases and judgement of therapeutic effect in patients with silent Leukoaraiosis.",,"Zheng, L. S.;Xu, J.;Wang, J. P.",2006,15,,0,
48,Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition,"We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer's disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (beta = -0.61, s.e. = 0.06) was four times stronger than that of AS (beta = -0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (beta = -0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (beta = -0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (beta = -0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.","Aged, 80 and over;Alzheimer Disease/complications/*pathology/psychology;Atrophy;Autopsy;Brain/*pathology;Brain Ischemia/complications/*pathology/psychology;Cognition Disorders/etiology/*pathology/psychology;Databases, Factual;Dementia, Vascular/complications/*pathology/psychology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prospective Studies","Zheng, L.;Vinters, H. V.;Mack, W. J.;Weiner, M. W.;Chui, H. C.",2016,Jan,10.1038/jcbfm.2015.152,0,
49,Differential effects of ischemic vascular disease and Alzheimer disease on brain atrophy and cognition,"We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction (CVD-path), and Alzheimer's disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (beta=-0.61, s.e.=0.06) was four times stronger than that of AS (beta=-0.15, s.e.=0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (beta=-0.13, s.e.=0.04). In contrast, the effects of AD pathology on global cognition (beta=-0.50, s.e.=0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (beta=-0.09, s.e.=0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.Journal of Cerebral Blood Flow & Metabolism advance online publication, 1 July 2015; doi:10.1038/jcbfm.2015.152.",,"Zheng, L.;Vinters, H. V.;Mack, W. J.;Weiner, M. W.;Chui, H. C.",2015,Jul 1,10.1038/jcbfm.2015.152,0,
50,MRI features of Creutzfeldt-Jakob disease,"Objective: To describe MR imaging findings of the brain in Creutzfeldt Jakob disease (CJD), and to evaluate the diagnostic usefulness of MRI in CJD. Methods: Four patients with biopsy proved CJD were reviewed. The imaging findings on conventional MRI and diffusion-weighted imaging (DWI) were retrospectively analyzed. The clinical symptoms and literature were also reviewed. Results: Bilateral high signal intensity on T2-weighted images in the deep white matter and corticospinal tracts was demonstrated in one case. In 2 cases, the symmetrical hyperintensities in the caudate nuclei and putamen were revealed and ribbon-like abnormalities in the cerebral cortex were showed on both T2-weighted and diffusion-weighted images. In one case, the ribbon-like abnormalities in the cerebral cortex were showed on both T2-weighted and diffusion-weighted images. Pronounced cerebral atrophy with widened sulci was also seen on MRI. Conclusion: CJD has some characteristic appearance on MRI, and therefore MRI is of great value in diagnosing the disease.",,"Zheng, K. H.;Ma, L.;Guo, Y.;Lin, W.;Huang, M. H.;Zhang, Y. Q.;Zhao, S. C.;Qian, M. Z.;Liang, Y. K.;Tao, L. B.",2006,20,,0,
51,Malnutrition-inflammation is a risk factor for cerebral small vessel diseases and cognitive decline in peritoneal dialysis patients: A cross-sectional observational study,"Background: Chronic kidney disease patients have an increased prevalence of subclinical cerebrovascular diseases. Dialysis patients have severe vascular diseases burden. The cerebral small vessel diseases (CSVD) are difficult to find by clinical assessment. The evaluation of CVSD needs MRI. Cognitive impairment is a consequence of CVSD which is diagnosed by cognitive testing. These limited the study of CVSD and cognitive function in dialysis patients. Peritoneal dialysis (PD) patients are minority of dialysis population. We know even fewer about the CVSD in this special population. Methods: In this cross-sectional study, we enrolled 72 PD patients who received care at the Peking Union Medical College hospital peritoneal dialysis center. CSVD were assessed by brain MR images. Cognitive function was evaluated with the Chinese version of the MMSE and MoCA. Results: In our PD patients, the brain MRI showed the prevalence different signs of CSVD were: lacunar infarcts 38.9%, microbleeds 36.1%, abnormal brain white matter hyperintensities (WMHs) 48.6%, and intracerebral hemorrhage 4.2%. 25% and 86.8%of our patients could be diagnosed as cognitive impairment, according to the MMSE and MoCA test, respectively. nPCR was lower in patients with a lacunar infarct or intracerebral hemorrhage, and relative to the MMSA/MoCA score; hsCRP was higher in patients with lacunar infarct or abnormal WMHs and negative relative to the MMSA/MoCA score. In logistic regression analyses, nPCR was an independent risk factor for lacunar infarcts and impaired cognitive function. The presence of lacunar infarct was an independent risk factor for cognitive function decline. Conclusion: We demonstrated a high prevalence of CSVD and cognitive impairment in our PD patients. Lacunar infarct was the main kind of CVSD responsible for PD patients cognitive function decline. Our novel observation also revealed an association between malnutrition-inflammation and CSVD.",nuclear magnetic resonance scanner;C reactive protein;adolescent;adult;aged;article;brain hemorrhage;cerebrovascular disease;China;cognitive defect;cross-sectional study;female;human;inflammation;lacunar stroke;major clinical study;male;malnutrition;mental deterioration;metabolic parameters;Mini Mental State Examination;Montreal cognitive assessment;normalized protein catabolic rate;nuclear magnetic resonance imaging;observational study;peritoneal dialysis;white matter lesion;DISCOVERY MR750,"Zheng, K.;Wang, H.;Hou, B.;You, H.;Yuan, J.;Luo, K.;Chen, L.;Li, M.;Xu, Q.;Zhu, Y.;Cui, L.;Nigwekar, S. U.;Feng, F.;Li, X.",2017,,10.1186/s12882-017-0777-1,0,
52,White matter hyperintensities are an independent predictor of physical decline in community-dwelling older people,"Background: Ageing is associated with physical disability, but little is known about the influence of white matter hyperintensities (WMHs) on physical function decline in older people. Objective: To investigate the role of WMHs as a predictor of decline in physical function in cognitively intact older people. Methods: 287 community-dwelling people aged 70-90 years underwent the Physiological Profile Assessment (PPA) and assessments of total and regional WMH volumes, cognitive function and comorbidities. Participants underwent reassessment of the PPA 12 months later, and those in the top quartile for increases in PPA scores over the year were regarded as having declined physically. Results: Multivariate logistic regression analyses revealed that people with WMH volumes in the 4th quartile showed greater physical decline (odds ratio 3.02, 95% confidence interval 1.02-8.95) while controlling for age, baseline physical function, general health, physical activity and cognitive function. Subsequent univariate analyses indicated that WMHs in the deep fronto-parietal and periventricular parieto-occipital regions had the strongest associations with physical decline. Conclusions: These findings indicate that WMHs are an independent predictor of decline in physical function and suggest that interventions that focus on preventing the development or progression of white matter lesions may help preserve physical function in older people. Copyright © 2012 S. Karger AG, Basel.",age distribution;aged;article;brain size;cognition;comorbidity;disease association;executive function;female;frontal lobe;functional disease;functional status;health status;human;major clinical study;male;occipital lobe;parietal lobe;physical activity;physical disability;priority journal;prospective study;spinal cord dorsal horn;task performance;white matter hyperintensity;white matter injury,"Zheng, J. J. J.;Delbaere, K.;Close, J. C. T.;Sachdev, P.;Wen, W.;Brodaty, H.;Lord, S. R.",2012,,,0,
53,Relationship between changes of event-related potential P300 and cognitive function disorder in patients with vascular dementia,"Aim: To evaluate the clinical value of event-related potential P300 as assessment of cognitive function disorder in the patients with vascular dementia (VD). Methods: Event-related potential P300 was tested with electrophysiological technique, cognitive functions were assessed with mini-mental state examination (MMSE), brief screening scale for dementia (BSSD) and Raven's standard progressive matrices (RSPM), and volumes of cerebral lobes and hippocampal formation were measured with MRI method in 30 ischemic VD patients, 30 cerebral infarction (CI) patients without dementia and 30 normal controls. Results: 1 P300 peak latency in VD patients [(435.57 ± 89.95) ms] was obviously longer than that of CI patients [(367.77 ± 29.14) ms] and normal controls [(341.90 ± 29.27) ms] (F = 5.16, P < 0.01). 2 P300 peak latency was negatively correlated with the scores of MMSE and BSSD (r = -0.87, -0.89, t = 6.89, 7.05, P < 0.01) in VD patients. 3 The volumes of frontal and temporal lobes in VD patients [(15.19 ± 1.51) %, (4.57 ± 0.51 ) %] were smaller than those of normal controls [(16.72 ± 1.46) %, (4.92 ± 0.50) %] respectively (T = 2.85, P < 0.01; T = 2.21, P < 0.05). 4 P300 peak latency was negatively correlated with the volumes of frontal and temporal lobes in vascular dementia patients (r = -0.56, -0.62, t = 5.53, 6.65, P < 0.01). Conclusion: The prolongation of P300 peak latency reflects the pathological changes of brain areas associated with cognitive function and the degree of cognitive function disorder in VD patients.",article;brain infarction;brain ischemia;brain region;clinical article;cognition;cognitive defect;controlled study;correlation analysis;diagnostic value;disease severity;electrophysiology;event related potential;female;frontal lobe;hippocampus;human;latent period;male;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;screening test;temporal lobe,"Zheng, J.;Zhao, X. Y.;Li, F. P.",2004,,,0,
54,Unusual brain images of a boy with adolescent cerebral X-linked adrenoleukodystrophy presenting with exhibitionism: A CARE-compliant case report,"Rationale: The respective involvements of both the thalamus and exhibitionism in cerebral X-linked adrenoleukodystrophy (X-ALD) have not been reported. Patient concerns: An 11-year-old boy initially presented with exhibitionism and progressive neurobehavioral symptoms. He subsequently developed transient urinary and fecal incontinence, and an unwillingness to eat or communicate. Diagnoses: We conducted contrast-enhanced brain magnetic resonance imaging (MRI), which revealed symmetrical altered signal intensities in bilateral frontal white matter, the basal ganglia, and dorsal thalami, as well as a peripheral rim of contrast enhancement. Diagnosis of adolescent cerebral X-ALD was confirmed on the basis of next generation genetic sequencing analysis. Interventions: We initiated the patient on hormonal replacement therapy. Outcomes: We observed rapidly progressive neurologic deterioration in this patient, and the boy fell into a vegetative state 10 months after discharge. Lessons: We recommend that physicians should not disregard X-ALD in patients with isolated psychiatric symptoms, including hypersexual behavior. The combination of detailed clinical evaluation, MRI, and next generation genetic sequencing can expedite the diagnostic process of atypical variant of X-ALD.",chloride;corticotropin;methylphenidate;n acetylaspartic acid;protein;adolescent disease;adrenoleukodystrophy;article;attention deficit disorder;basal ganglion;brain malformation;case report;child;Chinese;clinical article;clinical examination;communication disorder;diffusion weighted imaging;eating disorder;electroencephalogram;exhibitionism disorder;feces incontinence;gene mutation;hormone substitution;hospital discharge;human;hyperactivity;male;masturbation;mental deterioration;neuroimaging;next generation sequencing;persistent vegetative state;priority journal;protein cerebrospinal fluid level;Sanger sequencing;school child;spectroscopy;thalamus;urine incontinence;white matter;x linked adrenoleukodystrophy,"Zheng, F.;Lin, Z.;Ye, X.;Shi, X.",2017,,10.1097/md.0000000000009481,0,
55,Clinical and imaging features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (report of one family),"Objective: To investigate the clinical and imaging features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Methods: Clinical data of a Chinese Mongolian patient with CARASIL were analyzed retrospectively and pedigree investigation was carried out in the family. Results: The proband's parents were cousin and her brother was a patient with CARASIL too. The patients had onset at 25 and 23 years old, respectively. Clinical manifestations included cerebral stroke, progressive motor and mental deterioration, seizures, alopecia, and ocular fundus arteriosclerosis. No common risk factors of cerebral stroke were found in the family. Brain MRI showed bilateral diffuse cerebral white matter lesion with multiple infarcts and O'Sullivan sign. Cervical vertebral MRI showed multiple protrusion of intervertebral disc and significant retrogression. Conclusions: CARASIL is clinically characterized by young-age-onset cerebral stroke, cerebral arteriosclerosis, alopecia, cervical and lumbar spondylopathy. MRI shows multiple cerebral infarcts, leukoencephalopathy and retrogression of intervertebral disc.",,"Zheng, D. M.;Xu, F. F.;Zhang, H.",2009,2009,,0,
56,A structural MRI study on semantic dementia,"Objective: To analyze the structural changes of cerebral gray and white matter in patients with semantic dementia (SD), and to promote the knowledge of its pathological changes and mechanisms. Methods: Sixteen SD patients and 17 normal controls were scanned with a 3.0T MR scanner and the whole brain three-dimensional high-resolution structural images and diffusion tensor imaging (DTI) images were acquired. The gray matter density and fractional anisotropy (FA) values of white matter fiber tracts were analyzed by professional statistical softwares or packages respectively. The statistical analysis of gray matter density and FA values between 2 groups were processed by two sample t test, and the statistical threshold were set as P<0.001, Voxel≤338 and P<0.001, Voxel≤103 respectively. Results: Compared with the healthy controls, SD patients appeared significantly reduced gray matter density in bilateral temporal lobes, particularly in temporal pole. In addition, SD group showed more areas with grey matter loss in the left cerebral hemisphere, including the left inferior temporal gyrus, left supramarginal gyrus, left inferior parietal gyrus and left middle frontal gyrus. SD group also showed an obviously lower FA value in bilateral white matters of temporal lobe, including bilateral uncinate fasciculus, left cingulum (hippocampus) and bilateral fronto-occipital fasciculus. The abnormal areas of gray matter and white matter showed a high consistency in their anatomical connection. Conclusions: The study helps to reveal the pathological and anatomical basis of semantic dementia, and provides objective evidence for understanding the pathogenesis of semantic dementia.",,"Zhao, Z.;Yang, Y. H.;Lu, C. M.;Zhou, A. H.;Li, K. C.",2014,Apr.,,0,
57,Age-related differences in the topological efficiency of the brain structural connectome in amnestic mild cognitive impairment,"Amnestic mild cognitive impairment (aMCI) is accompanied by the accelerated cognitive decline and rapid brain degeneration with aging. However, the age-related alterations of the topological organization of the brain connectome in aMCI patients remained largely unknown. In this study, we constructed the brain structural connectome in 51 aMCI patients and 51 healthy controls by diffusion magnetic resonance imaging and deterministic tractography. The different age-related alteration patterns of the global and regional network metrics between aMCI patients and healthy controls were assessed by a linear regression model. Compared with healthy controls, significantly decreased global and local network efficiency in aMCI patients were found. When correlating network efficiency with age, we observed a significant decline in network efficiency with aging in the aMCI patients, while not in the healthy controls. The age-related decreases of nodal efficiency in aMCI patients were mainly distributed in the key regions of the default-mode network, such as precuneus, anterior cingulate gyrus, and parahippocampal gyrus. In addition, age-related decreases in the connection strength of the edges between peripheral nodes were observed in aMCI patients. Moreover, the decreased regional efficiency of the parahippocampal gyrus was correlated with impaired memory performances in patients. The present study suggests an age-related disruption of the topological organization of the brain structural connectome in aMCI patients, which may provide evidence for different neural mechanisms underlying aging in aMCI and may serve as a potential imaging marker for the early diagnosis of Alzheimer's disease.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Amnesia/ diagnostic imaging/ pathology/psychology;Brain/ diagnostic imaging/ pathology;Cognitive Dysfunction/ diagnostic imaging/ pathology/psychology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Humans;Linear Models;Male;Memory;Middle Aged;White Matter/diagnostic imaging/pathology;Aging;Brain connectome;Diffusion MRI;Graph theory;Mild cognitive impairment;White matter","Zhao, T.;Sheng, C.;Bi, Q.;Niu, W.;Shu, N.;Han, Y.",2017,Nov,,0,
58,Changes in serum cellular adhesion molecule and matrix metalloproteinase-9 levels in patients with cerebral infarction following hyperbaric oxygen therapy: A case and intergroup control study,"Background: Animal studies have confirmed that hyperbaric oxygen (HBO) therapy can reduce matrix metalloproteinase activity and blood brain barrier permeability, thereby exhibiting neuroprotective effects. However, at present, consensus does not exist in terms of its clinical efficacy. Objective: To validate the significance of changes in serum cellular adhesion molecule and MMP-9 levels in patients with cerebral infarction following HBO therapy. Design, time and setting: This randomized, controlled, neurobiochemical study was performed at the Department of Neurology, Affiliated Hospital of Qingdao University Medical College between December 2002 and March 2006. Participants: A total of 112 patients with acute cerebral infarction of internal carotid artery, comprising 64 males and 48 females, averaging (67 + 11) years, were recruited and randomized to a HBO group (n = 50) and a routine treatment group (n = 62). An additional 30 gender- and age-matched normal subjects, consisting of 17 males and 13 females, averaging (63 + 9) years, were enrolled as control subjects. Methods: The routine treatment group received routine drug treatment and rehabilitation exercise. HBO treatment was additionally performed in the HBO group, once a day, for a total of 10 days. Main outcome measures: Serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were detected by enzyme linked immunosorbent assay. Results: Upon admission, serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were significantly increased in patients with cerebral infarction, compared with control subjects (P < 0.01). Following HBO and routine treatments, serum levels of the above-mentioned indices were significantly reduced in the HBO and routine treatment groups (P < 0.01). Moreover, greater efficacy was observed in the HBO group, compared with the routine treatment group (P < 0.05 or P < 0.01). Conclusion: Intergroup comparison and case-control results indicated that HBO noticeably reduced serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9.",acute disease di [Diagnosis] acute disease dt [Drug Therapy] acute disease rh [Rehabilitation] adult aged article brain infarction di [Diagnosis] brain infarction dt [Drug Therapy] brain infarction rh [Rehabilitation] carotid artery disease clinical tri,"Zhao, R.;Wang, C.;Wang, Y.",2008,,,0,
59,Later onset metachromatic leukodystrophy diagnosed by nerve biopsy,"Three cases of later onset metachromatic leukodystrophy in one family were reported. The brother is 32 years old, younger sister is 35 years old and the elder sister is 39 years old, who were normal as child without any family history of neurological disease. The three cases began their illness at about the age of 30 years old with dysarthria, progressive dementia, motor disturbance and numbness in the extremities. CT scan showed low density in the white matter of frontal, parietal lobes and around the ventricle. The written reports of CT scan were lacunar infarction in brother, multiple lacunar infarction in younger sister and Binswanger's disease in elder sister. Nerve biopsy showed myelinated fibers were decreased in number. Metachromatical materials were seen in and around the Schwann cell cytoplasm. Metachromatical materials were lamillar inclusions in granular matrix by electromicroscopic examination. So nerve biopsy is easy, safe and effective method to diagnose the uncertain pathogenic leukoence-phalopathy.",adult;article;biopsy;case report;cell inclusion;differential diagnosis;family health;female;genetics;human;male;metachromatic leukodystrophy;pathology;peroneus nerve;Schwann cell;ultrastructure,"Zhao, J. X.",1992,,,0,
60,Correlation analysis between cognitive impairment and traditional Chinese medicine syndrome after acute cerebral infarction,"Aim: To investigate the correlation between the cognitive impairment (CI) and traditional Chinese medicine (TCM) syndromes after acute cerebral infarction (ACI), and provide data for early intervention in poststroke CI with TCM. Methods: Totally 41 post-ACI patients with CT, selected from the Department of Neurology, Yueyang Hospital of Combination of Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine from September 2003 to March 2004, were assessed by using the neuropsychological examination scales, and according to the scale for the differentiation of syndromes of vascular dementia, the quantitative scores, TCM syndromes differentiation were defined for quantitative scoring. Results: The most common TCM syndrome of CI after ACI was kidney-essence deficiency. The other ones were mentality obstruction by phlegm-turbidness, fu-organ turbidness stagnation, blood stagnation blocked in branch channel, exuberance of internal heat toxin, hyperactivity of liver-yang and Qi-blood deficiency. It was found that there was a marked correlation between the neuropsychological examination scores and the scales of TCM syndromes by the correlation analysis. (1) There was a negative correlation between the syndrome of mentality obstruction by phlegm-turbidness and mini-mental state examination (MMSE) (P < 0.01), calculation ability, copy score, memory score, symbol digit number, cancellation number (P < 0.05), and a significantly positive correlation with trail making test 1 and 2 (P < 0.01), and cancellation time (P < 0.05). (2) There was a negative correlation between the syndrome of fu-organ turbidness stagnation and copy score, memory score, cancellation number (P < 0.01), symbol digit number (P < 0.05), and a significantly positive correlation with the trail making test 2 (P < 0.05). Conclusion: Among the post-ACI CI patients, the TCM syndromes of kidney-essence deficiency, mentality obstruction by phlegm-turbidness, and fu-organ turbidness stagnation are common. There is a remarkable correlation between the cognitive impairment and the two following syndromes, namely, the syndrome of mentality obstruction by phlegm-turbidness and fu-organ turbidness stagnation. The post-ACI CI is a result of many factors collaboration with each other among them. Phlegm-turbidness and fu-organ are important pathologic factors causing cognitive impairment. TCM can be used to improve cognitive function in the post-ACI CI patients with the syndromes of mentality obstruction by phlegm-turbidness and fu-organ turbidness stagnation.",acute disease;article;brain infarction;calculation;Chinese medicine;clinical article;cognitive defect;controlled study;correlation analysis;human;mental disease;Mini Mental State Examination;neurologic disease;neuropsychological test;psychologic test;rating scale;scoring system;traditional chinese medicine syndrome,"Zhao, H.;Zhang, Q. J.;Zhou, Y.;Wang, T.;Guo, Q. H.",2005,,,0,
61,Thyroid function and plasma homocysteine level in vascular dementia patients,"Aim: To study the relationship between thyroid function and plasma homocysteine (Hcy) levels in patients with vascular dementia (VD). Methods: Totally 38 VD patients and 40 nondemented patients with cerebral infarction detected by CT, who hospitalized in the Department of Neurology, Affiliated Renmin Hospital of Yunyang Medical College between February 2004 and December 2005, were recruited in the study. The VD patients and controls matched each other well in gender and age. And the VD patients were graded with Mini-Mental State Examination (MMSE) scores as illiteracy (≤ 17 points), primary educated (education time ≤ 6 years, ≤ 20 points) and secondary educated or above (education time > 6 years, ≤ 24 points). Their thyroiedine and plasma, Hcy levels were measured by using radioimmunoassay and high-performance liquid chromatography with electrochemical detection, respectively. All the VD patients were tested by the professional researchers with MMSE, Hanchinski Ischemic Score (HIS) and Geriatric Depression Scale (GDS) within 24 hours after hospitalization. The severity of cognition impairment in VD patients was classified by MMSE's scores: mild (20-24 points), moderate (10-19 points) and severe (< 10 points). Results: All the 38 VD patients and 40 controls completed the detections and entered the result analysis.(1)The levels of triiodothyronine (T3), thyroxine (T4) and free T3 (FT3) were all obviously lower in VD patients than in controls [T3: (0.9±0.4), (1.3±0.3) μg/L t=5.012 9, P=0.000 0]; [T4: (92.9±26.4), (110.2±28.7) μg/L, t=2.766 6, P=0.007 1]; [FT3: (3.9±1.8), (7.2±2.1) pmol/L, t=7.433 6, P=0.000 0]. However, total plasma Hcy levels were higher in VD patients, compared with the patients with nondemented cerebral infarction [(29.57±7.12), (24.53±4.98) μmol/L, t=3.637 7, P =0.000 5]. There was no significant difference in the levels of free thyroxin (FT4) and thyroid-stimulating hormone (TSH) between the two groups (P > 0.05).(2) Plasma Hcy, FT3 and T3 concentrations were different significantly in VD patients with different severities of cognition impairment [FT3: (4.7±0.4), (3.5±0.5), (3.1±0.3) pmol/L, t=32.4, P=0.000 0]; [T3: (1.02+0.2), (0.9±0.1), (0.8±0.1) μg/L, t=5.91, P=0.006 1]; [Hcy: (26.52±4.84), (29.59±5.56), (32.71±6.17) μmol/L, F=3.59, P=0.038 0). While the levels of T4 FT4, and TSH were similar in the two groups (P > 0.05). Conclusion: The reduction of thyroiodine and increased levels of Hcy occur in VD patients, and they may be indicative factors for VD's severity.",homocysteine;liothyronine;thyrotropin;thyroxine;adult;aged;amino acid blood level;article;brain infarction;China;clinical article;cognitive defect;controlled study;disease severity;educational status;electrochemical detection;female;free liothyronine index;Geriatric Depression Scale;high performance liquid chromatography;human;liothyronine blood level;male;Mini Mental State Examination;multiinfarct dementia;radioimmunoassay;thyroid function;thyrotropin blood level;thyroxine blood level,"Zhao, B.;Zhang, J. J.;Wang, S. F.;Chen, G. H.;Hu, F. Y.",2006,,,0,
62,Combined measurement of thyroid and plasma homocysteic acid for detecting the severity of vascular dementia,"Background: Recent researches demonstrate that onset of cerebral infarction always accompanies with obvious changes of function of thyroid axis; while, high-homocysteic acidemia has been proved as one of risk factors of vascular dementia and Alzheimer disease. Meanwhile, it is found that level of plasma homocysteic acid is positive correlation with injured degrees of cognitive function and brain damage. Objective: To observe the changes of function of thyroid and level of homocysteic acid among patients with vascular dementia and compare with those patients without dementia cerebral infarction. Design: Randomized grouping and contrast observation. Setting: Department of Neurology, People's Hospital Affiliated to Yunyang Medical College, South China Hospital of Wuhan University. Participitants: A total of 38 patients with vascular dementia were hospitalized in the Department of Neurology, People's Hospital Affiliated to Yunyang Medical College from February 2004 to December 2005. All patients met the diagnostic criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) established by American Psychiatric Association. Based on educational degrees, Mini-mental Status Examination (MMSE) was classified into illiteracy (≤ 17 points), education of primary school (educational duration ≤ 6 years, ≤ 24 points) and education of middle school or above (educational duration > 6 years, ≤ 24 points). Forty patients with non-dementia cerebral infarction were regarded as the control group and checked with CT examination. There were no significant differences of sex and age between the two groups. All patients and relatives were provided the consent. Methods: Within 24 hours after hospitalization, patients with vascular dementia received MMSE scores, and the degrees were classified based on the scoring results: mild (20-24 points), moderate (10-19 points) and severe (below 10 points). Levels of thyroxine were measured with radioimmunodetection and content of homocysteic acid was measured with high performance liquid chromatogram (HPLC) electrochemical detection. Main outcome measures: Levels of homocysteic acid and thyroxine among patients with vascular dementia and non-dementia cerebral infarction. Results: A total of 38 patients with vascular dementia and 40 patients with non-dementia cerebral infarction were involved in the final analysis. 1 Levels of triiodothyronine (T3), thyroxine (T4) and free T3 (FT3) were (0.9±0.4) μg/L, (92.9±26.4) μg/L and (3.9±1.8) pmol/L in vascular dementia group respectively, which were higher than those in control group [(1.3±0.3) μg/L, (110.2±28.7) μg/L, (7.2±2.1) pmol/L, t=2.766 6-7.433 6, P < 0.01]; while, level of homocysteic acid was (29.57±7.12) μmol/L in vascular dementia group, which was higher than that in control group [(24.53±4.98) μmol/L, t=3.637 7, P < 0.01]. There were no significant differences of free T4 (FT4) and thyrotropic-stimulating hormone (TSH) between the two groups (P > 0.05). 2 Levels of FT3 of patients with mild, moderate and severe vascular dementia were (1.0±0.2), (0.9±0.1) and (0.8±0.1) μg/L, respectively; levels of homocysteic acid were (26.52μ4.84), (29.59μ5.56) and (32.71μ6.17) μmol/L, respectively. There were significant differences among patients at the three degrees of vascular dementia (F=3.59-32.4, P < 0.01). However, there were no significant differences of T4, FT4 and TSH among the three kinds of patients (P > 0.05). Conclusion: Levels of thyroxine of patients with vascular dementia decrease; however, levels of homocysteic acid increase. Therefore, the results can indirectly reflect severities of vascular dementia.",homocysteic acid;liothyronine;thyrotropin;thyroxine;adult;aged;amino acid blood level;article;brain infarction;clinical article;computer assisted tomography;controlled study;disease severity;female;free liothyronine index;free thyroxine index;high performance liquid chromatography;human;liothyronine blood level;male;measurement;Mini Mental State Examination;multiinfarct dementia;radioimmunoassay;thyroid function;thyroid gland;thyrotropin blood level;thyroxine blood level,"Zhao, B.;Zhang, J. J.;Wang, S. F.;Chen, G. H.;Hu, F. Y.",2006,,,0,
63,Value of CT and MRI features in evaluating patients with Binswanger disease,"Aim: To investigate the risk factors, clinical features and image changes of",,"Zhang, Z. L.;Wang, H.;Yin, Y. H.;Song, Y.;Li, G. Z.",2004,Nov,,0,
64,MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes,"Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy. © 2013 - IOS Press and the authors. All rights reserved.",,"Zhang, Y.;Tartaglia, M. C.;Schuff, N.;Chiang, G. C.;Ching, C.;Rosen, H. J.;Gorno-Tempini, M. L.;Miller, B. L.;Weiner, M. W.",2013,2013,,0,
65,Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease,"BACKGROUND: Neuroimaging in mild cognitive impairment (MCI) and Alzheimer disease (AD) generally shows medial temporal lobe atrophy and diminished glucose metabolism and cerebral blood flow in the posterior cingulate gyrus. However, it is unclear whether these abnormalities also impact the cingulum fibers, which connect the medial temporal lobe and the posterior cingulate regions. OBJECTIVE: To use diffusion tensor imaging (DTI), by measuring fractional anisotropy (FA), to test 1) if MCI and AD are associated with DTI abnormalities in the parahippocampal and posterior cingulate regions of the cingulum fibers; 2) if white matter abnormalities extend to the neocortical fiber connections in the corpus callosum (CC); 3) if DTI improves accuracy to separate AD and MCI from healthy aging vs structural MRI. METHODS: DTI and structural MRI were preformed on 17 patients with AD, 17 with MCI, and 18 cognitively normal (CN) subjects. RESULTS: FA of the cingulum fibers was significantly reduced in MCI, and even more in AD. FA was also significantly reduced in the splenium of the CC in AD, but not in MCI. Adding DTI to hippocampal volume significantly improved the accuracy to separate MCI and AD from CN. CONCLUSION: Assessment of the cingulum fibers using diffusion tensor imaging may aid early diagnosis of Alzheimer disease.","Aged;Aged, 80 and over;Alzheimer Disease/classification/ diagnosis;Cognition Disorders/classification/ diagnosis;Diffusion Magnetic Resonance Imaging/ methods;Female;Gyrus Cinguli/ pathology;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Parahippocampal Gyrus/pathology","Zhang, Y.;Schuff, N.;Jahng, G. H.;Bayne, W.;Mori, S.;Schad, L.;Mueller, S.;Du, A. T.;Kramer, J. H.;Yaffe, K.;Chui, H.;Jagust, W. J.;Miller, B. L.;Weiner, M. W.",2007,Jan 2,10.1212/01.wnl.0000250326.77323.01,0,
66,White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI,"Frontotemporal dementia (FTD) and Alzheimer's disease are sometimes difficult to differentiate clinically because of overlapping symptoms. Using diffusion tensor imaging (DTI) measurements of fractional anisotropy (FA) can be useful in distinguishing the different patterns of white matter degradation between the two dementias. In this study, we performed MRI scans in a 4 Tesla MRI machine including T1-weighted structural images and diffusion tensor images in 18 patients with FTD, 18 patients with Alzheimer's disease and 19 cognitively normal (CN) controls. FA was measured selectively in specific fibre tracts (including corpus callosum, cingulum, uncinate and corticospinal tracts) as well as globally in a voxel-by-voxel analysis. Patients with FTD were associated with reductions of FA in frontal and temporal regions including the anterior corpus callosum (P < 0.001), bilateral anterior (left P < 0.001; right P = 0.005), descending (left P < 0.001; right P = 0.003) cingulum tracts, and uncinate tracts (left P < 0.001; right P = 0.005), compared to controls. Patients with Alzheimer's disease were associated with reductions of FA in parietal, temporal and frontal regions including the left anterior (P = 0.003) and posterior (P = 0.002) cingulum tracts, bilateral descending cingulum tracts (P < 0.001) and left uncinate tracts (P < 0.001) compared to controls. When compared with Alzheimer's disease, FTD was associated with greater reductions of FA in frontal brain regions, whereas no region in Alzheimer's disease showed greater reductions of FA when compared to FTD. In conclusion, the regional patterns of anisotropy reduction in FTD and Alzheimer's disease compared to controls suggest a characteristic distribution of white matter degradation in each disease. Moreover, the white matter degradation seems to be more prominent in FTD than in Alzheimer's disease. Taken together, the results suggest that white matter degradation measured with DTI may improve the diagnostic differentiation between FTD and Alzheimer's disease.","Adult;Aged;Alzheimer Disease/diagnosis/pathology;Cross-Sectional Studies;Dementia/diagnosis/ pathology;Diagnosis, Differential;Diffusion Magnetic Resonance Imaging/methods;Female;Frontal Lobe/ pathology;Humans;Image Interpretation, Computer-Assisted/methods;Male;Middle Aged;Temporal Lobe/ pathology","Zhang, Y.;Schuff, N.;Du, A. T.;Rosen, H. J.;Kramer, J. H.;Gorno-Tempini, M. L.;Miller, B. L.;Weiner, M. W.",2009,Sep,10.1093/brain/awp071,0,
67,"Joint assessment of structural, perfusion, and diffusion MRI in Alzheimer's disease and frontotemporal dementia","Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD. Copyright © 2011 Yu Zhang et al.",adult;aged;Alzheimer disease;article;brain degeneration;brain perfusion;clinical article;controlled study;diagnostic value;differential diagnosis;diffusion weighted imaging;female;frontotemporal dementia;gray matter;human;image analysis;image processing;image reconstruction;male;morphology;neuroimaging;perfusion weighted imaging;priority journal;white matter,"Zhang, Y.;Schuff, N.;Ching, C.;Tosun, D.;Zhan, W.;Nezamzadeh, M.;Rosen, H. J.;Kramer, J. H.;Gorno-Tempini, M. L.;Miller, B. L.;Weiner, M. W.",2011,,10.4061/2011/546871,0,
68,"Joint assessment of structural, perfusion, and diffusion MRI in Alzheimer's disease and frontotemporal dementia","Most MRI studies of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have assessed structural, perfusion and diffusion abnormalities separately while ignoring the relationships across imaging modalities. This paper aimed to assess brain gray (GM) and white matter (WM) abnormalities jointly to elucidate differences in abnormal MRI patterns between the diseases. Twenty AD, 20 FTD patients, and 21 healthy control subjects were imaged using a 4 Tesla MRI. GM loss and GM hypoperfusion were measured using high-resolution T1 and arterial spin labeling MRI (ASL-MRI). WM degradation was measured with diffusion tensor imaging (DTI). Using a new analytical approach, the study found greater WM degenerations in FTD than AD at mild abnormality levels. Furthermore, the GM loss and WM degeneration exceeded the reduced perfusion in FTD whereas, in AD, structural and functional damages were similar. Joint assessments of multimodal MRI have potential value to provide new imaging markers for improved differential diagnoses between FTD and AD.",,"Zhang, Y.;Schuff, N.;Ching, C.;Tosun, D.;Zhan, W.;Nezamzadeh, M.;Rosen, H. J.;Kramer, J. H.;Gorno-Tempini, M. L.;Miller, B. L.;Weiner, M. W.",2011,,10.4061/2011/546871,0,67
69,MRI markers for mild cognitive impairment: comparisons between white matter integrity and gray matter volume measurements,"The aim of the study was to evaluate the value of assessing white matter integrity using diffusion tensor imaging (DTI) for classification of mild cognitive impairment (MCI) and prediction of cognitive impairments in comparison to brain atrophy measurements using structural MRI. Fifty-one patients with MCI and 66 cognitive normal controls (CN) underwent DTI and T1-weighted structural MRI. DTI measures included fractional anisotropy (FA) and radial diffusivity (DR) from 20 predetermined regions-of-interest (ROIs) in the commissural, limbic and association tracts, which are thought to be involved in Alzheimer's disease; measures of regional gray matter (GM) volume included 21 ROIs in medial temporal lobe, parietal cortex, and subcortical regions. Significant group differences between MCI and CN were detected by each MRI modality: In particular, reduced FA was found in splenium, left isthmus cingulum and fornix; increased DR was found in splenium, left isthmus cingulum and bilateral uncinate fasciculi; reduced GM volume was found in bilateral hippocampi, left entorhinal cortex, right amygdala and bilateral thalamus; and thinner cortex was found in the left entorhinal cortex. Group classifications based on FA or DR was significant and better than classifications based on GM volume. Using either DR or FA together with GM volume improved classification accuracy. Furthermore, all three measures, FA, DR and GM volume were similarly accurate in predicting cognitive performance in MCI patients. Taken together, the results imply that DTI measures are as accurate as measures of GM volume in detecting brain alterations that are associated with cognitive impairment. Furthermore, a combination of DTI and structural MRI measurements improves classification accuracy.","Aged;Aged, 80 and over;Anisotropy;Biomarkers/analysis;Brain Mapping;Case-Control Studies;Cerebral Cortex/ pathology/physiopathology;Diffusion Tensor Imaging;Female;Hippocampus/ pathology/physiopathology;Humans;Male;Middle Aged;Mild Cognitive Impairment/diagnosis/ pathology/physiopathology;Neuropsychological Tests;Parietal Lobe/ pathology/physiopathology;Sensitivity and Specificity;Temporal Lobe/ pathology/physiopathology","Zhang, Y.;Schuff, N.;Camacho, M.;Chao, L. L.;Fletcher, T. P.;Yaffe, K.;Woolley, S. C.;Madison, C.;Rosen, H. J.;Miller, B. L.;Weiner, M. W.",2013,,10.1371/journal.pone.0066367,0,
70,Occipital cortical gyrification reductions associate with decreased functional connectivity in amyotrophic lateral sclerosis,"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscular weakness and atrophy. Several morphometric studies have been conducted to investigate the gray matter volume or thickness changes in ALS, whereas the cortical folding pattern remains poorly understood. In the present study, we applied a surface-based local gyrification index (LGI) from high resolution MRI data to quantify the cortical folding in matched samples of 25 ALS patients versus 25 healthy controls. Using resting-state fMRI data, we further conducted seed-based functional connectivity analysis to explore the functional correlate of the cortical folding changes. We found that ALS patients had significantly reduced LGI in right occipital cortex and that abnormality in this region associated with decreased functional connectivity in the bilateral precuneus. This set of findings was speculated to result from disturbed white matter connectivity in ALS. In the patient group, we revealed significant negative correlations between disease duration and the LGIs of a cluster in the left superior frontal gyrus, which may reflect the cognitive deterioration in ALS. In summary, our results suggest that LGI may provide a useful means to assess ALS-related neurodegeneration and to study the pathophysiology of ALS.",adult;amyotrophic lateral sclerosis;article;clinical article;controlled study;disease duration;echo planar imaging;female;functional connectivity;functional magnetic resonance imaging;human;local gyrification index;male;mental deterioration;middle aged;nervous system parameters;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;occipital cortex;pathophysiology;priority journal;superior frontal gyrus;surface property,"Zhang, Y.;Fang, T.;Wang, Y.;Guo, X.;Alarefi, A.;Wang, J.;Jiang, T.;Zhang, J.",2017,,10.1007/s11682-015-9499-9,0,
71,Occipital cortical gyrification reductions associate with decreased functional connectivity in amyotrophic lateral sclerosis,"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscular weakness and atrophy. Several morphometric studies have been conducted to investigate the gray matter volume or thickness changes in ALS, whereas the cortical folding pattern remains poorly understood. In the present study, we applied a surface-based local gyrification index (LGI) from high resolution MRI data to quantify the cortical folding in matched samples of 25 ALS patients versus 25 healthy controls. Using resting-state fMRI data, we further conducted seed-based functional connectivity analysis to explore the functional correlate of the cortical folding changes. We found that ALS patients had significantly reduced LGI in right occipital cortex and that abnormality in this region associated with decreased functional connectivity in the bilateral precuneus. This set of findings was speculated to result from disturbed white matter connectivity in ALS. In the patient group, we revealed significant negative correlations between disease duration and the LGIs of a cluster in the left superior frontal gyrus, which may reflect the cognitive deterioration in ALS. In summary, our results suggest that LGI may provide a useful means to assess ALS-related neurodegeneration and to study the pathophysiology of ALS.",amyotrophic lateral sclerosis;clinical article;congenital malformation;functional magnetic resonance imaging;human;mental deterioration;nerve degeneration;occipital cortex;plant seed;precuneus;quantitative study;rest;superior frontal gyrus;white matter,"Zhang, Y.;Fang, T.;Wang, Y.;Guo, X.;Alarefi, A.;Wang, J.;Jiang, T.;Zhang, J.",2016,,,0,70
72,Effects of Dexamethasone in the Treatment of Recurrent Chronic Subdural Hematoma,"Objective Recurrent chronic subdural hematoma (CSDH) is not rare. Some studies have demonstrated the role of dexamethasone in the medical management of chronic subdural hematoma. However, no systematic study in the treatment of recurrent CSDH has been published. The aim of our study is to evaluate the efficacy and safety of dexamethasone in patients with recurrent CSDH. Methods We retrospectively reviewed medical records of consecutive patients from July 2010 to September 2014. A total of 27 patients with symptomatic recurrent CSDH were included in the analysis. Follow-up for each patient consisted of computed tomography or magnetic resonance imaging every 28 days from admission to the resolution of hematoma. Data were collected on hematoma volume, complications, and outcome. Results Among the 27 patients, 3 patients with recurrent CSDH were only treated by burr hole surgery. Of the other 24 patients who primarily underwent dexamethasone treatment, 17 (70.8%) patients were treated successfully with medical treatment, whereas 7 patients required reoperation. Complications were noted in 3 (12.5%) patients (1 hyperglycemia, 1 urinary tract infection, and 1 pneumonia). There was 1 mortality (4.2%) for massive brain infarction. Twenty-one of the 24 patients (87.5%) recovered to their previous functional levels. There was no statistical significance in Fisher text between surgery and dexamethasone regarding success, complication, and functional recovery rate. Conclusions Patients with recurrent CSDH can be treated successfully and safely with the nonsurgical medical treatment of dexamethasone. By use of this method, reoperation may be avoided.",dexamethasone;omeprazole;adult;aged;article;brain infarction;clinical article;computer assisted tomography;confusion;conservative treatment;corticosteroid therapy;craniotomy;dementia;drowsiness;drug dose reduction;drug effect;drug efficacy;drug safety;drug treatment failure;female;follow up;gait disorder;Glasgow coma scale;headache;hemiparesis;hospital admission;human;hyperglycemia;male;medical record review;middle aged;neurosurgery;nuclear magnetic resonance imaging;outcome assessment;pneumonia;recurrent disease;reoperation;retrospective study;subdural hematoma;surgical drainage;urinary tract infection;very elderly;x-ray computed tomography,"Zhang, Y.;Chen, S.;Xiao, Y.;Tang, W.",2017,,10.1016/j.wneu.2017.05.135,0,
73,Brain Atrophy Correlates with Severe Enlarged Perivascular Spaces in Basal Ganglia among Lacunar Stroke Patients,"BACKGROUND: Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke. METHODS: We prospectively identified patients with lacunar stroke (diameter on DWI </= 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (+/- 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS. RESULTS: During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS. CONCLUSIONS: Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.",,"Zhang, X.;Ding, L.;Yang, L.;Qin, W.;Yuan, J.;Li, S.;Hu, W.",2016,,10.1371/journal.pone.0149593,0,
74,Investigation on correlation between diabetes combined with stroke and multiple infarctional dementia,,sugar;aged;article;cerebrovascular accident;chi square test;China;comorbidity;computer assisted tomography;controlled study;correlation function;diabetes mellitus;diagnostic test;disease association;early diagnosis;female;follow up;glucose blood level;human;major clinical study;male;medical examination;multiinfarct dementia;neurology;nuclear magnetic resonance imaging;statistical significance;symptomatology;treatment planning,"Zhang, X.",2003,,,0,
75,The microvascular changes in cases of hereditary multi-infarct disease of the brain,"A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.",,"Zhang, W. W.;Ma, K. C.;Andersen, O.;Sourander, P.;Tollesson, P. O.;Olsson, Y.",1994,1994,,0,
76,Enhancing Diffusion MRI Measures By Integrating Grey and White Matter Morphometry With Hyperbolic Wasserstein Distance,"In order to improve the preclinical diagnose of Alzheimer's disease (AD), there is a great deal of interest in analyzing the AD related brain structural changes with magnetic resonance image (MRI) analyses. As the major features, variation of the structural connectivity and the cortical surface morphometry provide different views of structural changes to determine whether AD is present on presymptomatic patients. However, the large scale tensor-valued information and relatively low imaging resolution in diffusion MRI (dMRI) have created huge challenges for analysis. In this paper, we propose a novel framework that improves dMRI analysis power by fusing cortical surface morphometry features from structural MRI (sMRI). We first compute the hyperbolic harmonic maps between cortical surfaces with the landmark constraints thus to precisely evaluate surface tensor-based morphometry. Meanwhile, the graph-based analysis of structural connectivity derived from dMRI is conducted. Next, we fuse these two features via the optimal mass transportation (OMT) and eventually the Wasserstein distance (WD) based single image index is computed as a potential clinical multimodality imaging score. We apply our framework to brain images of 20 AD patients and 20 matched healthy controls, randomly chosen from the Alzheimer's Disease Neuroimaging Initiative (AD-NI2) dataset. Our preliminary experimental results of group classification outperformed those of some other single dMRI-based features, such as regional hippocampal volume, mean scores of fractional anisotropy (FA) and mean axial (MD). The novel image fusion pipeline and simple imaging score of structural changes may benefit the preclinical AD and AD prevention research.",Alzheimer's Disease;Fusion;Graph Laplacian;Morphometry;Wasserstein Distance,"Zhang, W.;Shi, J.;Yu, J.;Zhan, L.;Thompson, P. M.;Wang, Y.",2017,,,0,
77,Correlation between brain magnetic resonance imaging and blood inflammatory markers for patients with vascular cognitive impairment,"Objective: The aim was to research the correlation between brain magnetic resonance imaging and blood inflammatory markers for patients with varying degrees of vascular cognitive impairment. Methods: Total 90 subjects were divided into vascular cognitive impairment with no dementia, vascular dementia and control group. The Chinese version of the Montreal Cognitive Assessment, Clinical Dementia Rating, activities of daily living scale and Hachinski Ischemic Scale were used for tests; the magnetic resonance imaging consisted of routine scanning sequences, susceptibility weighted imaging and diffusion tensor imaging; cardiopulmonary resuscitation, interleukin-6 and tumor necrosis factor-α were detected by enzyme-linked immunosorbent assay. Results: Microbleeds mainly appeared under the cortex of frontal lobe and temporal lobe and in the basal ganglia, centrum semiovale, corona radiate and thalamus; the number of the microbleeding parts were larger than those of the vascular cognitive impairment with no dementia. The fractional anisotropy values in the parts under the cortex of frontal lobe and temporal lobe and in the basal ganglia, centrum semiovale, corona radiate and thalamus were lower than those of the vascular cognitive impairment with no dementia and the apparent diffusion coefficient values increased. Cardiopulmonary resuscitation, interleukin-6 and tumor necrosis factor-αlevel of the vascular dementia were higher than those of the vascular cognitive impairment with no dementia. Conclusion: It was valuable for early diagnosis of vascular cognitive impairment and assessment of its severity to detect microbleeds by the susceptibility weighted imaging on magnetic resonance, examine Leukoaraiosis by the diffusion tensor imaging and the levels of serum inflammatory markers.",Avanto 1.5 T;nuclear magnetic resonance scanner;interleukin 6;tumor necrosis factor;adult;aged;article;basal ganglion;cognitive defect;controlled study;corona radiata (brain);diffusion tensor imaging;female;fractional anisotropy;frontal lobe;human;inflammation;major clinical study;male;nuclear magnetic resonance imaging;resuscitation;susceptibility weighted imaging;temporal lobe;thalamus;thalamus medialis centralis nucleus;vascular cognitive impairment,"Zhang, W.;Lin, Y.;Lai, J.;Quan, Y.;Du, Y.;Li, X.",2017,,,0,
78,Investigation of the risk factors for leukoaraiosis (LA),"Leukoaraiosis (LA) describes abnormal changes in the cerebral white matter frequently seen on CT and MRI in older adults. Its appearance indicates mild brain injury, and it is often regarded as a mark of senile dementia. Through the analysis of related risk factors of 6000 patients with LA diagnosed by cranial MRI in our department, we found that age, cerebral infarction, lacunar infarction, history of brain hemorrhage, and increased triglycerides were risk factors for LA, and the relative risk odds ratio values were 2.135 (95% confidence interval [CI] = 1.874-2.501), 3.330 (95% CI = 1.922-3.997), 3.412 (95% CI = 2.986-3.512), 3.611 (95% CI = 2.054-9.147), and 1.457 (95% CI = 1.058-1.769), respectively. Through the identification of the risk factors for LA and effective interventions, the occurrence of dementia, stroke, and premature death may be effectively prevented.","Adult;Age Distribution;Aged;Aged, 80 and over;Analysis of Variance;Brain/ pathology;Cerebral Infarction/epidemiology;Female;Humans;Intracranial Hemorrhages/epidemiology;Leukoaraiosis/ diagnosis/ epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Stroke, Lacunar/epidemiology;Triglycerides/blood;Young Adult","Zhang, S.;Kang, X.",2013,Jul,10.1177/1010539513493111,0,
79,Association of White Matter Integrity and Cognitive Functions in Chinese Non-Demented Elderly with the APOE ε 4 Allele,"The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). This study aimed to investigate abnormality of white matter integrity and its relationship to cognitive impairments in Chinese non-demented elderly with and without the ε4 allele. We assessed cognitive differences using a series of neuropsychological tests and assessed white matter integrity using tract-based spatial statistics to measure mean diffusivity and fractional anisotropy. We determined that there were no statistically significant group differences in any neuropsychological measures. However, APOE ε4 carriers without cognitive decline exhibited widespread disruption of the white matter tracts in several areas, including the cingulum, fornix, corpus callosum, and corona radiate. Furthermore, a correlation analysis in ε4 carriers indicated that disruption of the right fornix stria terminalis and the genu of the corpus callosum were positively associated with cognitive impairment, including memory, executive function, spatial processing, attention, and language. The present study reveals the deleterious effects of the ε4 allele on white matter, and this damage may potentially serve as a biomarker in preclinical investigations. Our promising results encourage further investigation using a multidimensional longitudinal approach with larger samples.",apolipoprotein E4;biological marker;aged;allele;Alzheimer disease;article;attention;behavior;brain fornix;brain region;Chinese;cingulum (brain);cognition;cognitive defect;corona radiata (brain);corpus callosum;correlation analysis;diffusion tensor imaging;executive function;female;fractional anisotropy;genetic association;genotype;heterozygote;human;language;major clinical study;male;memory;neuropsychological test;nuclear magnetic resonance scanner;spatial behavior;stria terminalis;white matter;white matter injury,"Zhang, S.;Chen, Y.;Liu, Z.;Zhang, J.;Li, X.;Cui, R.;Zhang, Z.;Lei, H.",2015,,,0,
80,Association of White Matter Integrity and Cognitive Functions in Chinese Non-Demented Elderly with the APOE varepsilon4 Allele,"The apolipoprotein E (APOE) varepsilon4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). This study aimed to investigate abnormality of white matter integrity and its relationship to cognitive impairments in Chinese non-demented elderly with and without the varepsilon4 allele. We assessed cognitive differences using a series of neuropsychological tests and assessed white matter integrity using tract-based spatial statistics to measure mean diffusivity and fractional anisotropy. We determined that there were no statistically significant group differences in any neuropsychological measures. However, APOEvarepsilon4 carriers without cognitive decline exhibited widespread disruption of the white matter tracts in several areas, including the cingulum, fornix, corpus callosum, and corona radiate. Furthermore, a correlation analysis in varepsilon4 carriers indicated that disruption of the right fornix stria terminalis and the genu of the corpus callosum were positively associated with cognitive impairment, including memory, executive function, spatial processing, attention, and language. The present study reveals the deleterious effects of the varepsilon4 allele on white matter, and this damage may potentially serve as a biomarker in preclinical investigations. Our promising results encourage further investigation using a multidimensional longitudinal approach with larger samples.",,"Zhang, S.;Chen, Y.;Liu, Z.;Zhang, J.;Li, X.;Cui, R.;Zhang, Z.",2015,,10.3233/jad-150357,0,
81,Diffusion characteristics of subcortical structures in patients with subcortical ischemic vascular disease and its correlation to cognitive function,"OBJECTIVE: To explore the diffusion-tensor imaging (DTI) characteristics of normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) on conventional magnetic resonance imaging (MRI) in patients with subcortical ischemic vascular disease (SIVD) and examine the relation of such features with the general cognitive function of the patients. METHODS: DTI was performed in 46 SIVD patients and 34 age-matched control subjects with normal MRI findings. The apprarent diffusion coeeficient (ADC) and fractional anisotropy (FA) were measured within the regions of white matter lesions (WMLs), NAWM and NAGM. All the subjects were examined by neurologists with MMSE and clinical neurologic examination. RESULTS: Compared with normal controls, SIVD subjects showed increased ADC values in the subcortical NAGM and NAWM in anterior periventricular and centrum semiovale, with decreased FA values in the caudate nucleus, thalamus and centrum semiovale. An increased severity of the WMLs was associated with increased ADC and decreased FA in the NAWM of SIVD patients. After controlling for age, the ADC in the NAWM of the posterior periventricular, NAWM and WMLs in the centrum semiovale, caudate nucleus and thalamus showed significant inverse correlations to MMSE; FA values in NAWM of the anterior periventricular and WMLs of the centrum semiovale were positively correlated to MMSE. CONCLUSION: In SIVD patients, the NAWM and NAGM regions shown by MRI contain diffusion abnormalities, and these abnormalities shown by DTI are significantly correlated to the general cognitive function of the patients.","Aged;Anisotropy;Brain Ischemia/ physiopathology/psychology;Case-Control Studies;Cerebral Cortex/ pathology;Cognition/physiology;Cognition Disorders/pathology/ physiopathology;Dementia, Vascular/pathology/ physiopathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Middle Aged","Zhang, Q. J.;Guo, Y. M.;Yang, J. L.;Zhang, G. J.;Xu, M.;Bai, Z. L.",2011,Oct,,0,
82,Microvascular perfusion based on arterial spin labeled perfusion MRI as a measure of vascular risk in Alzheimer's disease,"There is growing recognition of an interaction between cerebrovascular disease and Alzheimer's disease, but the mechanisms of this interaction remain poorly understood. While macroscopic stroke can clearly produce cognitive deficits and accelerate Alzheimer's disease, the prevalence and implications of microvascular disease in Alzheimer's disease pathogenesis has been harder to define. At present, white matter (WM) lesions, primarily defined as hyperintensities seen on T2-weighted magnetic resonance imaging (MRI), provide the best biomarker of cerebrovascular disease at the microvascular level. However, T2 hyperintensities in WM can also be caused by other mechanisms such as inflammation. Arterial spin labeled (ASL) perfusion MRI provides a noninvasive approach for quantifying cerebral blood flow (CBF). We explored CBF measurements with ASL in AD patients, mild cognitive impairment patients, and an age-matched control group to determine if CBF in gray matter or WM could be correlated with WM lesions, or to stratify patients by microvascular disease severity. In a retrospective sample, we were able to obtain credible measures of WM CBF using ASL MRI and observed trends suggesting that WM CBF may provide a useful biomarker of microvascular disease. Future prospective studies in larger cohorts with optimized ASL MRI protocols will be needed to validate these observations. © 2012 - IOS Press and the authors. All rights reserved.",,"Zhang, Q.;Stafford, R. B.;Wang, Z.;Arnold, S. E.;Wolk, D. A.;Detre, J. A.",2012,2012,,0,
83,[Independent correlations of cerebral microstructural changes on DTI to general cognitive function and executive function in patients with subcortical ischemic vascular disease],"To investigate whether DTI abnormalities in patients with nondemented subcortical ischemic vascular disease (SIVD) are correlated to general cognitive function and executive function independent of conventional MRI parameters. Sixty-six SIVD patients including 30 with cognitive impairment without dementia (VCIND) and 36 with normal cognition (NCI) underwent DTI and cognitive assessment of the general cognitive function and executive function. Conventional MRI parameters and DTI parameters were measured within the white matter lesions (WMLs), normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM). The independent predictors of general cognitive function and executive function in SIVD patients was analyzed. NCI and VCIND patients showed significant differences in the periventricular WMLs, ADC valus in NAWM and WMLs of the centrum semiovale, and FA values in NAWM of the anterior periventricular. Except for ADC values of the caudate nucleus, ADC and FA values in the subcortical NAGM showed significant difference between the two groups. After controlling for age and education, PVLs and ADC values in the WMLs and NAWM of the centrum semiovale and putamen, and FA values in the anterior periventricular NAWM, WMLs and putamen showed significant correlations to MMSE; the number of lacunar infarcts, ADC values in posterior periventricular NAWM and caudate nucleus, and FA values in anterior periventricular NAWM and thalamus showed significant correlations to CDT. Multivariate analysis showed independent correlations of the ADC values in WMLs and NAWM of the centrum semiovale to MMSE, and demonstarted correlations of the ADC values of the caudate nucleus and number of lacunar infarcts to CDT. In nondemented SIVD subjects, the integrity of the white matter in the centrum semiovale strongly correlates to the general cognition, and the microstructural damage of the caudate nucleus head predicts executive function impairment independent of other MRI variables.",article;brain cortex;brain ischemia;case control study;caudate nucleus;cognition;cognitive defect;diffusion tensor imaging;human;nuclear magnetic resonance imaging;pathology;pathophysiology;physiology;psychological aspect,"Zhang, Q.;Guo, Y.;Bai, Z.;Yang, J.;Zhang, G.;Xu, M.",2012,,,0,
84,"An MRI brain atrophy and lesion index to assess the progression of structural changes in Alzheimer's disease, mild cognitive impairment, and normal aging: a follow-up study","BACKGROUND: A brain atrophy and lesion index (BALI) based on high-field magnetic resonance imaging (MRI) has recently been validated to evaluate structural changes in the aging brain. The present study investigated the two-year progression of brain structural deficits in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI), and in healthy control older adults (HC) using the BALI rating. METHODS: T1-weighted high-resolution anatomical imaging data using 3 Tesla MRI at baseline (AD = 39, MCI = 82, HC = 58) and at 24-months were obtained from the Alzheimer's disease Neuroimaging Initiative database. Lesions in various brain structures, including the infratentorial and basal ganglia areas, and the periventricular and deep white matter and global atrophy, were evaluated and combined into the BALI scale. RESULTS: Mean progression of brain deficits over two years was evident in all diagnostic groups (p < 0.001) and was statistically greater in MCI-AD converters than in the non-converters (p = 0.044). An increase in the BALI score was significantly associated with cognitive test scores (p = 0.008 for the Mini-Mental State Examination MMSE and p = 0.013 for the Alzheimer's Disease Assessment Scale-Cognitive Subscale ADAS-cog) in a model that adjusted for age, sex, and education. CONCLUSION: The BALI rating quantified the progression of brain deficits over two years, which is associated with cognitive decline. BALI ratings may be used to help summarize AD-associated structural variations.","Aged;Aged, 80 and over;Aging;Alzheimer Disease/ pathology;Atrophy/pathology;Brain/ pathology;Chi-Square Distribution;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/ pathology","Zhang, N.;Song, X.;Zhang, Y.;Chen, W.;D'Arcy, R. C.;Darvesh, S.;Fisk, J. D.;Rockwood, K.",2011,,10.3233/jad-2011-0048,0,
85,Learning-based structurally-guided construction of resting-state functional correlation tensors,"Functional magnetic resonance imaging (fMRI) measures changes in blood-oxygenation-level-dependent (BOLD) signals to detect brain activities. It has been recently reported that the spatial correlation patterns of resting-state BOLD signals in the white matter (WM) also give WM information often measured by diffusion tensor imaging (DTI). These correlation patterns can be captured using functional correlation tensor (FCT), which is analogous to the diffusion tensor (DT) obtained from DTI. In this paper, we propose a noise-robust FCT method aiming at further improving its quality, and making it eligible for further neuroscience study. The novel FCT estimation method consists of three major steps: First, we estimate the initial FCT using a patch-based approach for BOLD signal correlation to improve the noise robustness. Second, by utilizing the relationship between functional and diffusion data, we employ a regression forest model to learn the mapping between the initial FCTs and the corresponding DTs using the training data. The learned forest can then be applied to predict the DTI-like tensors given the initial FCTs from the testing fMRI data. Third, we re-estimate the enhanced FCT by utilizing the DTI-like tensors as a feedback guidance to further improve FCT computation. We have demonstrated the utility of our enhanced FCTs in Alzheimer's disease (AD) diagnosis by identifying mild cognitive impairment (MCI) patients from normal subjects.",Dti;Functional correlation tensor;Random forest;rs-fMRI,"Zhang, L.;Zhang, H.;Chen, X.;Wang, Q.;Yap, P. T.;Shen, D.",2017,Nov,,0,
86,The cranial MRI appearance of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in a family,"Objective: To recognize the cranial MRI appearance in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Five patients with CADASIL from two generations in a family underwent routine MRI and MRA examinations. Three patients with CADASIL were confirmed by the Notch3 genetic testing and the vascular pathological results and one was diagnosed on basis of MR and clinical manifestations. The imaging data from 4 patients with CADASIL were analyzed. Results: Four cases achieved preliminary diagnosis of CADASIL and one was excluded by MRI. In 4 patients with CADASIL, bilateral symmetrical, confluent white matter lesions in the subcortical and periventricular regions were seen frequently in the temporal, frontal and parietal lobes, but the occipital lobes were less involved. These lesions appeared as long T(1) and long T(2) signal. O'Sullivan sign was shown in all cases and subcortical lacunar lesions was seen in 2 cases. In the centrum semiovale, well-defined, round or oval cystic infarcts (black holes) were demonstrated in 3 cases and multiple tiny round enlarged perivascular spaces (pepperpot appearance) in all cases. The corpus callosum was involved in all cases, and it was evidently atrophic in 2 cases. The anterior part of internal capsule and external capsule were involved in all cases, which appeared as so called ""A"" shape sign on the axial T(2) WI. The lacunar infarcts were present in the basal ganglia and brainstem. Only one case revealed a small infarct in the right cerebellum. Four patients shared mild or moderate atrophy of brainstem, cerebellum and cerebrum. No marked abnormality of large vessels was seen in all cerebral MRA. Conclusions: The cranial MRI appearance in CADASIL shows some characteristics. MRI may give some information in the preliminary diagnosis or exclusion of CADASIL.",,"Zhang, J. P.;Sun, B. L.;Yu, Y. Q.;Pan, H.;Tang, Y. X.;Qian, Z.;Gao, P.;Liu, F.;Li, H. F.",2008,February,,0,
87,Association of serum vascular endothelial growth factor levels and cerebral microbleeds in patients with Alzheimer's disease,"BACKGROUND AND PURPOSE: The association between the presence of cerebral microbleeds (CMBs) and serum vascular endothelial growth factor (VEGF) levels in patients with Alzheimer's disease (AD) was investigated. METHODS: Consecutive AD patients who underwent magnetic resonance examination with susceptibility-weighted imaging (SWI) were prospectively examined. The presence of CMBs on SWI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex and risk factors were obtained. Serum VEGF levels were measured with an enzyme-linked immunosorbent assay. RESULTS: Of the 146 AD patients included, 47 (32.2%) patients had CMBs on SWI. The CMBs were most commonly located in strictly lobar locations (29/47, 61.7%). The mean VEGF levels were higher in the patients with CMBs than in those without (336.72 +/- 15.18 vs. 192.37 +/- 11.34 pg/ml). Multivariate logistic regression analyses showed that, for each 10 pg/ml increase of VEGF levels, there was a significant increase in the presence of CMBs after adjusting for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction and white matter hyperintensity in patients with AD (odds ratio 2.37; 95% confidence interval 1.53-4.02, P = 0.004). CONCLUSION: Serum VEGF levels are associated with the presence of CMBs in patients with AD.","0 (Vascular Endothelial Growth Factor A);Aged;Aged, 80 and over;Alzheimer Disease/ blood/complications/diagnostic imaging;Cerebral Hemorrhage/ blood/complications/diagnostic imaging;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Risk Factors;Stroke, Lacunar/blood/complications/diagnostic imaging;Vascular Endothelial Growth Factor A/ blood;Alzheimer's disease;cerebral microbleeds;serum;susceptibility-weighted imaging;vascular endothelial growth factor","Zhang, J. B.;Li, M. F.;Zhang, H. X.;Li, Z. G.;Sun, H. R.;Zhang, J. S.;Wang, P. F.",2016,Aug,,0,88
88,Association of serum vascular endothelial growth factor levels and cerebral microbleeds in patients with Alzheimer's disease,"BACKGROUND AND PURPOSE: The association between the presence of cerebral microbleeds (CMBs) and serum vascular endothelial growth factor (VEGF) levels in patients with Alzheimer's disease (AD) was investigated. METHODS: Consecutive AD patients who underwent magnetic resonance examination with susceptibility-weighted imaging (SWI) were prospectively examined. The presence of CMBs on SWI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex and risk factors were obtained. Serum VEGF levels were measured with an enzyme-linked immunosorbent assay. RESULTS: Of the 146 AD patients included, 47 (32.2%) patients had CMBs on SWI. The CMBs were most commonly located in strictly lobar locations (29/47, 61.7%). The mean VEGF levels were higher in the patients with CMBs than in those without (336.72 +/- 15.18 vs. 192.37 +/- 11.34 pg/ml). Multivariate logistic regression analyses showed that, for each 10 pg/ml increase of VEGF levels, there was a significant increase in the presence of CMBs after adjusting for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction and white matter hyperintensity in patients with AD (odds ratio 2.37; 95% confidence interval 1.53-4.02, P = 0.004). CONCLUSION: Serum VEGF levels are associated with the presence of CMBs in patients with AD.",,"Zhang, J. B.;Li, M. F.;Zhang, H. X.;Li, Z. G.;Sun, H. R.;Zhang, J. S.;Wang, P. F.",2016,Apr 29,10.1111/ene.13030,0,
89,Characterizing iron deposition in Parkinson's disease using susceptibility-weighted imaging: An in vivo MR study,"Brain-iron deposition has been proposed to play an important role in the pathophysiology of Parkinson's disease (PD). The aim of this study was to evaluate the feasibility of characterizing iron deposition in PD using susceptibility-weighted imaging (SWI), and to investigate the correlation of brain-iron accumulation with the clinical status in patients with PD. Forty patients with PD without dementia and 26 age- and sex-matched healthy controls underwent high-resolution susceptibility-weighted magnetic resonance (MR) imaging. The phase shift values of the bilateral red nucleus (RN), substantia nigra (SN), caudate nucleus (CA), globus pallidus (GP), putamen (PU), thalamus (TH) and frontal white matter (FWM) were examined for their relationship with the clinical status. The iron concentrations of the regions involved in PD, such as the SN, increased more significantly, while those in other regions of interest (ROI) did not elevate significantly. No correlation between the increase of the iron concentrations of the SN and duration of PD was observed. PD, however, was closely associated with the Unified Parkinson's Disease Rating Scale motor score (UPDRS-III). No significant differences were found between earlier-onset and later-onset PD patients in terms of the iron concentrations of the SN. Brain-iron concentration can be evaluated by SWI. Also, the brain-iron concentration in the SN correlated with UPDRS motor score, indicating that iron concentration can function as an in vivo biomarker to objectively evaluate the status of PD. © 2010 Elsevier B.V. All rights reserved.",,"Zhang, J.;Zhang, Y.;Wang, J.;Cai, P.;Luo, C.;Qian, Z.;Dai, Y.;Feng, H.",2010,12,,0,
90,White matter integrity disruptions associated with cognitive impairments in type 2 diabetic patients,"Type 2 diabetes mellitus (T2DM) is associated with a twofold increased risk of dementia and can affect many cognitive abilities, but its underlying cause is still unclear. In this study, we used a combination of a battery of neuropsychological tests and diffusion tensor imaging (DTI) to explore how T2DM affects white matter (WM) integrity and cognition in 38 T2DM patients and 34 age-, sex-, and education-matched normal control subjects. A battery of neuropsychological tests was used to assess a wide range of cognitive functions. Tract-based spatial statistics combined with region of interest-wise (ROI-wise) analysis of mean values of DTI metrics in ROIs was used to compare group differences of DTI metrics on WM skeletons to identify severely disrupted WM tracts in T2DM. We found that T2DM patients showed 1) various cognitive impairments, including executive function, spatial processing, attention, and working memory deficits; 2) widespread WM disruptions, especially in the whole corpus callosum, the left anterior limb of the internal capsule (ALIC.L), and external capsule (EC); and 3) a positive correlation between executive function and WM integrity in the ALIC.L and the left EC. In conclusion, T2DM patients show various cognitive impairments and widespread WM integrity disruptions, which we attribute to demyelination. Moreover, executive dysfunction closely correlates with WM abnormalities.","Aged;Cognition/ physiology;Cognition Disorders/pathology/physiopathology;Diabetes Mellitus, Type 2/ pathology/ physiopathology;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology/ physiopathology","Zhang, J.;Wang, Y.;Wang, J.;Zhou, X.;Shu, N.;Zhang, Z.",2014,Nov,10.2337/db14-0342,0,
91,Disrupted White Matter Network and Cognitive Decline in Type 2 Diabetes Patients,"Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline.",Alzheimer's disease;diffusion tensor imaging;graph theory;type 2 diabetes mellitus;white matter network,"Zhang, J.;Liu, Z.;Li, Z.;Wang, Y.;Chen, Y.;Li, X.;Chen, K.;Shu, N.;Zhang, Z.",2016,May 6,10.3233/jad-160111,0,
92,Relationship between vascular stenosis and cognition in leukoaraiosis patients,"OBJECTIVE: To explore the relationship between the degree of vascular stenosis and cognition in leukoaraiosis patients. METHODS: A total of 101 leukoaraiosis patients from the Department of Neurology, The First Affiliated Hospital of Anhui Medical University between September 2013 and June 2014, divided into two groups:patients with cognitive impairment (SVCI) (n = 54) , and those without cognitive impairment (NC) (n = 47) . All patients were enrolled and examined by magnetic resonance imaging (MRI) scanning and magnetic resonance angiography (MRA) or computed tomography angiography (CTA). The cognitive assessments were made by MMSE (mini-mental state examination), CAMCOG-C (Cambridge cognitive examination-Chinese version) and CDR (clinical dementia rating). The severity of leukoaraiosis and vascular stenosis was graded by MRI and MRA/CTA scans. RESULTS: The degree of vascular stenosis group and the severity of LA in SVCI were significantly higher than NC (2.0 +/- 0.8 vs1.1 +/- 0.6, 2.6 +/- 1.0 vs 2.0 +/- 1.0; P = 0.020, P = 0.003). As white matter level aggravated, cognitive function decreased and vascular stenosis deteriorated accordingly, and the score of MMSE (25 +/- 4, 24 +/- 6, 22 +/- 4) and CAMCOG-C (83 +/- 14, 80 +/- 14, 73 +/- 14) has a statistical significance (P = 0.012, P = 0.014). At the same time, the negative correlation was found in LA patients between cognitive function and severity of LA (r = -0.317, P = 0.001) as well as degree of vascular stenosis (r = -0.284, P = 0.004). Multivariate Logistic regression analysis revealed that, after controlling for various factors, both severity of LA (OR = 2.025, 95% CI 1.307-3.954) and the degree of vascular stenosis (OR = 1.812, 95% CI 1.129-2.908) were risk factors for cognitive impairment in leukoaraiosis patients. CONCLUSION: Cognition of leukoaraiosis patients is correlated with both severity of leukoaraiosis and vascular stenosis.","Cognition;Cognition Disorders;Constriction, Pathologic;Dementia;Humans;Leukoaraiosis;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Neuropsychological Tests;Risk Factors;White Matter","Zhang, C.;Zhou, X.;Wang, L.;Liu, H.;Zhu, M.;Sun, Z.",2015,Jan 6,,0,
93,Functional MRI and cognition assessment in subcortical ischemic vascular disease,"OBJECTIVE: To evaluate the imaging features of patients with vascular cognitive impairment (VCI) induced by Subcortical Ischemic Vascular Disease (SIVD), through magnetic resonance diffusion tensor imaging (DTI) and proton spectroscopy (MRS) technology. METHODS: A total of 52 patients with SIVD were enrolled. After analysis of scale score, 32 patients with cognitive impairment were assigned to VCI group and 20 patients with no cognitive impairment were assigned to control group. Both group received DTI and MRS examination. The mean values of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the bilateral temporal, frontal, parietal and occipital white matter regions as well as in the bilateral centrum semiovale were calculated. The peak value of MRS of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and phaseomannite (mI) were calculated. RESULTS: Compared with control group, FA decreased in the region of temporal, frontal, parietal as well as in the centrum semiovale, and ADC increased in VCI group (P < 0.05). In the frontal regions and centrum semiovale, the VCI patients had a significant FA decrease. The ADC value increased obviously in the temporal lobe. Spectrum analysis results showed, NAA/Cr was lower than control group in VCI group in the frontal lobe (1.43 +/- 0.08 vs 1.53 +/- 0.92), while mI/Cr was higher than control group in the temporal lobe (0.51 +/- 0.06 vs 0.46 +/- 0.07) (P < 0.05). CONCLUSION: FA in the temporal and centrum semiovale regions of VCI group and NAA in the temporal white matter regions decreased obviously. DTI and MRS could provide a reference value for early diagnosis and assessment of VCI.","Aged;Aged, 80 and over;Brain Ischemia/ physiopathology/ psychology;Cognition Disorders/pathology/ physiopathology;Dementia, Vascular/pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Zhang, B.;Wen, C. Y.;Wang, L.;Zhang, X.",2011,May,,0,
94,Characterization of white matter degeneration in elderly subjects by magnetic resonance diffusion and FLAIR imaging correlation,"Fluid attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) techniques have been widely used to evaluate white matter (WM) alterations associated with aging, dementia and cerebral vascular disease. The relationship between FLAIR detected WM lesions (WML) and DTI detected WM integrity changes, however, remains unclear. To investigate this association, voxelwise correlations between 4 Tesla DTI and FLAIR images from elderly subjects were performed by relating WML volume and intensity in FLAIR to fractional anisotropy (FA) and mean diffusivity (MD) in DTI. Significant DTI-FLAIR correlations were found in regions overlapping with the WML of moderate intensities in FLAIR. No significant correlations were detected in periventricular regions where the FLAIR intensities are particularly high. The findings are consistent with a transitional model for WM degeneration from normal WM to cerebrospinal fluid (CSF). The results show that the correlation between DTI and FLAIR disappears when the FLAIR intensity of WML reaches its maximum at a certain lesion severity, and that the correlations may remerge with reversed signs when the lesion severity is further increased. These results suggest that the different stages of WM degeneration in elderly subjects can be better characterized by regional DTI-FLAIR correlations than single modality alone. © 2009 Elsevier Inc. All rights reserved.",aged;article;brain degeneration;cerebrospinal fluid;computer model;controlled study;diffusion tensor imaging;disease severity;female;fluid attenuated inversion recovery;human;image analysis;image display;image quality;imaging;male;neuroimaging;priority journal;white matter,"Zhan, W.;Zhang, Y.;Mueller, S. G.;Lorenzen, P.;Hadjidemetriou, S.;Schuff, N.;Weiner, M. W.",2009,,10.1016/j.neuroimage.2009.02.004,0,95
95,Characterization of white matter degeneration in elderly subjects by magnetic resonance diffusion and FLAIR imaging correlation,"Fluid attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) techniques have been widely used to evaluate white matter (WM) alterations associated with aging, dementia and cerebral vascular disease. The relationship between FLAIR detected WM lesions (WML) and DTI detected WM integrity changes, however, remains unclear. To investigate this association, voxelwise correlations between 4 Tesla DTI and FLAIR images from elderly subjects were performed by relating WML volume and intensity in FLAIR to fractional anisotropy (FA) and mean diffusivity (MD) in DTI. Significant DTI-FLAIR correlations were found in regions overlapping with the WML of moderate intensities in FLAIR. No significant correlations were detected in periventricular regions where the FLAIR intensities are particularly high. The findings are consistent with a transitional model for WM degeneration from normal WM to cerebrospinal fluid (CSF). The results show that the correlation between DTI and FLAIR disappears when the FLAIR intensity of WML reaches its maximum at a certain lesion severity, and that the correlations may remerge with reversed signs when the lesion severity is further increased. These results suggest that the different stages of WM degeneration in elderly subjects can be better characterized by regional DTI-FLAIR correlations than single modality alone.",Aged;Anisotropy;Brain/ pathology;Computer Simulation;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Magnetic Resonance Imaging/methods;Male;Myelin Sheath/ pathology;Neurodegenerative Diseases/ pathology;Organ Size,"Zhan, W.;Zhang, Y.;Mueller, S. G.;Lorenzen, P.;Hadjidemetriou, S.;Schuff, N.;Weiner, M. W.",2009,Aug,10.1016/j.neuroimage.2009.02.004,0,
96,Efficacy observation of batroxobin for treatment of vascular cognitive impairment,"Objective: To investigate the efficacy and safety of batroxobin in the treatment of vascular cognitive impairment (VCI). Methods: Eighty patients with VCI (but did not reached to dementia) caused by ischemic cerebrovascular disease with cognitive impairment were enrolled. They were randomly allocated into a batroxobin group and a control group (n = 40 in each group). The patients in batroxobin group were administered intravenously with batroxobin ( 5 U batroxobin in 250 mL isotonic saline once a day, 4 times a week) at 1, 8, and 12 weeks after admission. All patients were administered aspirin routinely. The mini-mental state examination (MMSE) scale and activities of daily living (ADL) scale were used to assess the cognitive function and ADL; the levels of fibrinogen (FIB) were measured before and after treatment. The safety of the drug was assessed. Results: Circled digit oneThere were no significant difference in MMSE and ADL scores between the batroxobin and control groups before treatment and at 8 weeks after treatment (P>0.05). At 12 weeks, there were significant difference in MMSE and ADL scores compared to those before treatment (P<0.05 ), but there was no significant difference compared to the control group (P>0.05). At 16 weeks, there was significant improvement in MMSE and ADL scores compare to those before treatment and the control group (P<0.05), while there was no obvious change in MMSE and ADL scores at 8, 12, and 16 weeks in the control group compared to those before treatment (P > 0.05). circled digit 2FIB was 3.50 ± 0.59 and 1.95 ± 0.43 g/L before and after treatment at one week in the batroxobin group, at 8 weeks it was 3.22 ± 0.54 and 2.18 ± 0.46 g/L, and at 12 weeks it was 2.75 ± 0.41 and 2.40 ± 0.41g/L. The differences were statistically significant before and after treatment(P < 0.01). FIB was 3.39 ± 0.61, 3.30 ± 0.59, and 3.24 ± 0.56 g/L, respectively at 1, 8, and 12 weeks in the control group. There were no significant differences (P > 0.05). circled digit 3One patient in the batroxobin group and 2 in the control group had recurrent cerebral infarction(P > 0.05). No adverse events occurred, such as drug allergy, and intracranial or digestive hemorrhage in the batroxobin group. Conclusion: Batroxobin is contributive to improve the cognitive function in patients with VCI and improve their ADL. Moreover, its safety is good.",acetylsalicylic acid;batroxobin;fibrinogen;article;cerebrovascular disease;cognition;cognitive defect;computer assisted tomography;controlled study;daily life activity;drug efficacy;drug safety;Hamilton Depression Rating Scale;human;ischemia;major clinical study;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;rating scale;vascular cognitive impairment,"Zhai, Q. J.;Yue, X. Y.;Hong, Z.;Xu, G. L.;Liu, X. F.",2010,,,0,
97,Efficacy observation of batroxobin for treatment of vascular cognitive impairment. Chinese,"Objective: To investigate the efficacy and safety of batroxobin in the treatment of vascular cognitive impairment (VCI). Methods: Eighty patients with VCI (but did not reached to dementia) caused by ischemic cerebrovascular disease with cognitive impairment were enrolled. They were randomly allocated into a batroxobin group and a control group (n = 40 in each group). The patients in batroxobin group were administered intravenously with batroxobin ( 5 U batroxobin in 250 mL isotonic saline once a day, 4 times a week) at 1, 8, and 12 weeks after admission. All patients were administered aspirin routinely. The mini-mental state examination (MMSE) scale and activities of daily living (ADL) scale were used to assess the cognitive function and ADL; the levels of fibrinogen (FIB) were measured before and after treatment. The safety of the drug was assessed. Results: Circled digit oneThere were no significant difference in MMSE and ADL scores between the batroxobin and control groups before treatment and at 8 weeks after treatment (P>0.05). At 12 weeks, there were significant difference in MMSE and ADL scores compared to those before treatment (P<0.05 ), but there was no significant difference compared to the control group (P>0.05). At 16 weeks, there was significant improvement in MMSE and ADL scores compare to those before treatment and the control group (P<0.05), while there was no obvious change in MMSE and ADL scores at 8, 12, and 16 weeks in the control group compared to those before treatment (P > 0.05). circled digit 2FIB was 3.50 + 0.59 and 1.95 + 0.43 g/L before and after treatment at one week in the batroxobin group, at 8 weeks it was 3.22 + 0.54 and 2.18 + 0.46 g/L, and at 12 weeks it was 2.75 + 0.41 and 2.40 + 0.41g/L. The differences were statistically significant before and after treatment(P < 0.01). FIB was 3.39 + 0.61, 3.30 + 0.59, and 3.24 + 0.56 g/L, respectively at 1, 8, and 12 weeks in the control group. There were no significant differences (P > 0.05). circled digit 3One patient in the batroxobin group and 2 in the control group had recurrent cerebral infarction(P > 0.05). No adverse events occurred, such as drug allergy, and intracranial or digestive hemorrhage in the batroxobin group. Conclusion: Batroxobin is contributive to improve the cognitive function in patients with VCI and improve their ADL. Moreover, its safety is good.",article // cerebrovascular disease // cognition // cognitive defect/dt [Drug Therapy] // computer assisted tomography // controlled study // daily life activity // drug efficacy // drug safety // Hamilton scale // human // ischemia // major clinical stu,"Zhai, Q. J.;Yue, X. Y.;Hong, Z.;Xu, G. L.;Liu, X. F.",2010,,10.3969/j.issn.1672-5921.2010.02.005,0,
98,[Multi-infarct dementia under CT aspects] Zur Frage der Multiinfarktdemenz unter besonderer Berucksichtigung computertomographischer Befunde,"Multiinfarct- or vascular dementia can primarily be defined clinically by means of the combination of intermittent neurological deficits and progressive mental deterioration. Cranial computerized tomography is not capable of proving the intellectual state, but if there is clinical appearance of mental impairment, CCT is an important aid in providing some further clues as to the etiology of the complaints.","Cerebrovascular Disorders/complications;Dementia/ diagnosis;Humans;Terminology as Topic;Tomography, X-Ray Computed","Zeumer, H.;Hacke, W.",1982,Nov,,0,
99,Multi-infarct dementia especially regarding CT aspects,"Multi-infarct or vascular dementia can primarily be defined clinically by means of the combination of intermittent neurological deficits and progressive mental deterioration. Cranial computerized tomography is not capable of proving the intellectual state, but if there is clinical appearance of mental impairment, CCT is an important aid in providing some further clues as to the etiology of the complaints.",adult;aged;brain ischemia;central nervous system;clinical article;computer analysis;computer assisted tomography;dementia;diagnosis;human,"Zeumer, H.;Hacke, W.",1982,,,0,
100,[Multi-infarct dementia under CT aspects],"Multiinfarct- or vascular dementia can primarily be defined clinically by means of the combination of intermittent neurological deficits and progressive mental deterioration. Cranial computerized tomography is not capable of proving the intellectual state, but if there is clinical appearance of mental impairment, CCT is an important aid in providing some further clues as to the etiology of the complaints.","Cerebrovascular Disorders/complications;Dementia/*diagnosis;Humans;Terminology as Topic;*Tomography, X-Ray Computed","Zeumer, H.;Hacke, W.",1982,Nov,10.1055/s-2007-1002278,0,
101,Association of Cerebrospinal Fluid Neurofilament Light Concentration With Alzheimer Disease Progression,"IMPORTANCE: The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. OBJECTIVE: To test whether CSF NFL concentration is associated with cognitive decline and imaging evidence of neurodegeneration and white matter change in AD. DESIGN, SETTING, AND PARTICIPANTS: A commercially available immunoassay was used to analyze CSF NFL concentration in a cohort of patients with AD (n = 95) or mild cognitive impairment (MCI) (n = 192) and in cognitively normal individuals (n = 110) from the Alzheimer's Disease Neuroimaging Initiative. The study dates were January 2005 to December 2007. The NFL analysis was performed in November 2014. MAIN OUTCOMES AND MEASURES: Correlation was investigated among baseline CSF NFL concentration and longitudinal cognitive impairment, white matter change, and regional brain atrophy within each diagnostic group. RESULTS: Cerebrospinal fluid NFL concentration (median [interquartile range]) was higher in the AD dementia group (1479 [1134-1842] pg/mL), stable MCI group (no progression to AD during follow-up; 1182 [923-1687] pg/mL), and progressive MCI group (MCI with progression to AD dementia during follow-up; 1336 [1061-1693] pg/mL) compared with control participants (1047 [809-1265] pg/mL) (P < .001 for all) and in the AD dementia group compared with the stable MCI group (P = .01). In the MCI group, a higher CSF NFL concentration was associated with faster brain atrophy over time as measured by changes in whole-brain volume (beta = -4177, P = .003), ventricular volume (beta = 1835, P < .001), and hippocampus volume (beta = -54.22, P < .001); faster disease progression as reflected by decreased Mini-Mental State Examination scores (beta = -1.077, P < .001) and increased Alzheimer Disease Assessment Scale cognitive subscale scores (beta = 2.30, P < .001); and faster white matter intensity change (beta = 598.7, P < .001). CONCLUSIONS AND RELEVANCE: Cerebrospinal fluid NFL concentration is increased by the early clinical stage of AD and is associated with cognitive deterioration and structural brain changes over time. This finding corroborates the contention that degeneration of large-caliber axons is an important feature of AD neurodegeneration.",,"Zetterberg, H.;Skillback, T.;Mattsson, N.;Trojanowski, J. Q.;Portelius, E.;Shaw, L. M.;Weiner, M. W.;Blennow, K.",2016,Jan 1,10.1001/jamaneurol.2015.3037,0,
102,Gray and white matter degeneration revealed by diffusion in an Alzheimer mouse model,"In patients with Alzheimer's disease (AD) the severity of white matter degeneration correlates with the clinical symptoms of the disease. In this study, we performed diffusion-tensor magnetic resonance imaging at ultra-high field in a mouse model for AD (APP(swe)/PS1(dE9)) in combination with a voxel-based approach and tractography to detect changes in water diffusivity in white and gray matter, because these reflect structural alterations in neural tissue. We found substantial changes in water diffusion parallel and perpendicular to axonal tracts in several white matter regions like corpus callosum and fimbria of the hippocampus, that match with previous findings of axonal disconnection and myelin degradation in AD patients. Moreover, we found a significant increase in diffusivity in specific hippocampal subregions, which is supported by neuronal loss as visualized with Kluver-Barrera staining. This work demonstrates the potential of ultra-high field diffusion-tensor magnetic resonance imaging as a noninvasive modality to describe white and gray matter structural changes in mouse models for neurodegenerative disorders, and provides valuable knowledge to assess future AD prevention strategies in translational research.","Alzheimer Disease/ pathology;Animals;Disease Models, Animal;Hippocampus/ pathology;Humans;Mice;Mice, Transgenic;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology","Zerbi, V.;Kleinnijenhuis, M.;Fang, X.;Jansen, D.;Veltien, A.;Van Asten, J.;Timmer, N.;Dederen, P. J.;Kiliaan, A. J.;Heerschap, A.",2013,May,10.1016/j.neurobiolaging.2012.11.017,0,
103,Spreading along white matter tracts? - A case of progressive multifocal leukoencephalopathy with unusual MRI presentation,,antiretrovirus agent;C reactive protein;choline;cidofovir;adult;article;astrocytosis;basal ganglion;brain biopsy;brain stem;case report;CD4 lymphocyte count;CD8+ T lymphocyte;cerebellum;corpus callosum;cytotoxic T lymphocyte;disease severity;helper cell;hemiparesis;hospital admission;human;inflammation;internuclear ophthalmoplegia;JC virus;leukocyte count;lymphocyte proliferation;macrophage;male;medulla oblongata;neurologic examination;nuclear magnetic resonance imaging;primary motor cortex;primary progressive aphasia;progressive multifocal leukoencephalopathy;pyramidal tract;thrombocyte count;virus load;white matter,"Zeller, D.;Markulin, F.;Monoranu, C. M.;Solymosi, L.;Stoll, G.",2013,,,0,
104,Subcortical vascular dementia: Lights and shadows,"SIVD ""subcortical ischemic vascular dementia"" represents an important and homogeneous subtype of Vascular Dementia, related to small vessel disease that includes two different aspects, represented by the Binswanger's disease and lacunar state((1)). The syndrome is defined clinically by cognitive impairment and evidence of subcortical vascular brain injury, including lacunar infarcts (lacunar state's lesions) and deep white matter lesions (WMLs)((1)). Lacunar state and Binswanger's syndrome represent only a small part of a more complex disease. In fact, classification is difficult, remaining a not clear and universally accepted definition((1)). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms and short-stepped gait((2)). These manifestations probably result from ischemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia((2)). The involvement of these circuits has also been enhanced by the results obtained from neurophysiology studies, performed by transcranial magnetic stimulation (TMS) in patients with this form of dementia, showing cortical-excitability changes. Currently, brain imaging is necessary for the diagnosis, especially MRI. Many cardio-cerebrovascular risk factors are involved, but hypertension is the most important because it is the most correlated with the small vessel disease. Primary prevention of these risk factors is considered the best treatment for SIVD((2)).",,"Zelante, G.;Catalano, A.;Ricceri, R.;Rampello, L.",2012,2012,,0,
105,Voxel Level Survival Analysis of Grey Matter Volume and Incident Mild Cognitive Impairment or Alzheimer's Disease,"The purpose of this study was to identify, at the voxel level, brain regions associated with the time to develop mild cognitive impairment (MCI) or Alzheimer's disease (AD) from normal cognition. We analyzed incident MCI (n = 58) or AD (n = 151) in 292 cognitively normal participants in the Cardiovascular Health Study-Cognition Study (mean age = 79.2 +/- 3.6 years). We used segmented, modulated grey matter maps from 3D (spoiled gradient echo) MRI scans obtained in 1998/99 (with clinical follow-up through 2012) that were smoothed with a 3-D 4 mm Gaussian filter. We fit approximately 1.92 million voxel-level Cox proportional hazard models to examine the grey matter volume effect on time to event, adjusting for age, sex, and diabetes. We used the significance threshold of p < 0.005 with contiguity threshold of at least 68 voxels (false detection probability <2.5x10 -8). Areas within the mesial temporal lobe (MTL), anterior temporal lobe, hippocampus, and posterior cingulate gyrus were associated with time to MCI or AD. The presence of white matter lesions (a marker of small vessel disease in the brain) was associated with the volumes of the MTL and precuneus; MRI-identified infarcts also predicted MTL volume. These findings are important because we identified critical brain regions that predict a person's increased likelihood of developing MCI or AD over a decade prior to the onset of clinical symptoms; these critical brain regions were themselves affected by the presence of vascular disease.",Alzheimer's disease;Cox survival model;Mri;incidence;mild cognitive impairment,"Zeifman, L. E.;Eddy, W. F.;Lopez, O. L.;Kuller, L. H.;Raji, C.;Thompson, P. M.;Becker, J. T.",2015,,10.3233/jad-150047,0,
106,Reversibility of white matter changes and dementia after treatment of dural fistulas,We describe two patients with dural fistulas who presented with dementia and diffuse white matter signal changes on MR that significantly improved after surgery. One patient had preoperative embolization.,adult;article;artificial embolism;brain arteriovenous malformation;case report;clinical examination;dementia;dura mater;human;male;nuclear magnetic resonance imaging;preoperative treatment;white matter,"Zeidman, S. M.;Monsein, L. H.;Arosarena, O.;Aletich, V.;Biafore, J. A. M.;Dawson, R. C.;Debrun, G. M.;Hurko, O.",1995,,,0,
107,Change in multimodal MRI markers predicts dementia risk in cerebral small vessel disease,"OBJECTIVE: To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD). METHODS: In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined. RESULTS: Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia. A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85. CONCLUSIONS: This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions.","Aged;Aged, 80 and over;Cerebral Small Vessel Diseases/ complications;Cognition Disorders/diagnostic imaging/etiology;Cohort Studies;Dementia/ diagnostic imaging/ etiology;Female;Humans;Image Interpretation, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Multimodal Imaging/ methods;Neuropsychological Tests;Predictive Value of Tests;Psychiatric Status Rating Scales","Zeestraten, E. A.;Lawrence, A. J.;Lambert, C.;Benjamin, P.;Brookes, R. L.;Mackinnon, A. D.;Morris, R. G.;Barrick, T. R.;Markus, H. S.",2017,Oct 31,,0,
108,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel C82R mutation in the NOTCH3 gene,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease associated with mutations in the NOTCH3 gene on chromosome 19, and represents the most common hereditary stroke disorder. We describe a pedigree, which suffered the classical clinical CADASIL pattern of migraine headaches, recurrent subcortical infarcts, and subcortical dementia, associated with a previously undescribed missense mutation (c.[244T>C], p.[C82R]) in NOTCH3. This new mutation extends the list of known pathogenic mutations responsible for CADASIL, which are associated with an odd number of cysteine residues within any of the epidermal growth factor-like repeats of Notch3 receptor protein.","Aged;Arginine/*genetics;Brain/pathology;CADASIL/*genetics/pathology;Cysteine/*genetics;Family Health;Female;Genetic Association Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/*genetics;Receptors, Notch/*genetics;C82r;Cadasil;NOTCH3 mutation;Notch3 receptor protein;dementia;headache;migraine;stroke","Zea-Sevilla, M. A.;Bermejo-Velasco, P.;Serrano-Heranz, R.;Calero, M.",2015,,10.3233/jad-141218,0,
109,Psychotic crisis symptomatic of an outbreak of multiple sclerosis,"Mental disorders (especially depression and dementia) are highly prevalent among multiple sclerosis (MS) patients. Schizophrenic-type psychosis has been reported only rarely most often in advanced cases and its possible pathophysiological and even causal relation to the demyelinating disease is disputed. We describe a woman with MS who experienced 2 episodes of acute psychosis after having had only one prior episode of focal neurological dysfunction. The coincidence of psychiatric symptoms and the appearance of new white matter lesions in both hemispheres was confirmed by CT and MRI during the second episode. We suggest that in this patient the psychotic symptoms do not depend on the strategic anatomical location of plates, but rather on the effect of nonspecific lesions in a patient previously predisposed to psychiatric disorder.",adult;article;brain injury;case report;computer assisted tomography;female;human;multiple sclerosis;nuclear magnetic resonance;psychosis,"Zarranz, J. J.;Antiguedad, A. R.;Barcena, J.",1995,,,0,
110,Regional white matter integrity differentiates between vascular dementia and Alzheimer disease,"BACKGROUND AND PURPOSE: Considerable clinical and radiological overlap between vascular dementia (VaD) and Alzheimer disease (AD) often makes the diagnosis difficult. Diffusion-tensor imaging studies showed that fractional anisotropy (FA) could be a useful marker for white matter changes. This study aimed to identify regional FA changes to identify a biomarker that could be used to differentiate VaD from AD. METHODS: T1-weighted and diffusion-tensor imaging scans were obtained in 13 VaD patients, 16 AD patients, and 22 healthy elderly controls. We used tract-based spatial statistics to study regional changes in fractional anisotropy in AD, VaD, and elderly controls. We then used probabilistic tractography to parcel the corpus callosum in 7 regions according to its connectivity with major cerebral cortices using diffusion-tensor imaging data set. We compared the volume and mean FA in each set of transcallosal fibers between groups using ANOVA and then applied a discriminant analysis based on FA and T2-weighted imaging measures. RESULTS: FA reduction in forceps minor was the most significant area of difference between AD and VaD. Segmentation of the corpus callosum using tractography and comparison of FA changes of each segment confirmed the FA changes in transcallosal prefrontal tracts of patients with VaD when compared to AD. The best discriminant model was the combination of transcallosal prefrontal FA and Fazekas score with 87.5% accuracy, 100% specificity, and 93% sensitivity (P<0.0001). CONCLUSIONS: Integrating mean FA in the forceps minor to the Fazekas score provides a useful quantitative marker for differentiating AD from VaD.","Aged;Algorithms;Alzheimer Disease/ diagnosis/ pathology;Analysis of Variance;Anisotropy;Brain/ pathology;Cohort Studies;Corpus Callosum/pathology;Dementia, Vascular/ diagnosis/ pathology;Diagnosis, Differential;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male","Zarei, M.;Damoiseaux, J. S.;Morgese, C.;Beckmann, C. F.;Smith, S. M.;Matthews, P. M.;Scheltens, P.;Rombouts, S. A.;Barkhof, F.",2009,Mar,10.1161/strokeaha.108.530832,0,
111,Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease,"In this study we segment the hippocampus according to functional connectivity assessed from resting state functional magnetic resonance images in healthy subjects and in patients with Alzheimer's disease (AD). We recorded the resting FMRI signal from 16 patients and 22 controls. We used seed-based functional correlation analyses to calculate partial correlations of all voxels in the hippocampus relative to characteristic regional signal changes in the thalamus, the prefrontal cortex (PFC) and the posterior cingulate cortex (PCC), while controlling for ventricular CSF and white matter signals. Group comparisons were carried out controlling for age, gender, hippocampal volume and brain volume. The strength of functional connectivity in each region also was correlated with neuropsychological measures. We found that the hippocampus can be segmented into three distinct functional subregions (head, body, and tail), according to the relative connectivity with PFC, PCC and thalamus, respectively. The AD group showed stronger hippocampus-PFC and weaker hippocampus-PCC functional connectivity, the magnitudes of which correlated with MMSE in both cases. The results are consistent with an adaptive role of the PFC in the context of progression of dysfunction in PCC during earlier stages of AD. Extension of our approach could integrate regional volume measures for the hippocampus with their functional connectivity patterns in ways that should increase sensitivity for assessment of AD onset and progression.","Aged;Aged, 80 and over;Alzheimer Disease/ physiopathology;Brain Mapping/methods;Female;Hippocampus/ anatomy & histology/physiology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/ physiopathology;Neuropsychological Tests;Young Adult","Zarei, M.;Beckmann, C. F.;Binnewijzend, M. A.;Schoonheim, M. M.;Oghabian, M. A.;Sanz-Arigita, E. J.;Scheltens, P.;Matthews, P. M.;Barkhof, F.",2013,Feb 1,10.1016/j.neuroimage.2012.10.071,0,
112,Higher incidence of mild cognitive impairment in familial hypercholesterolemia,"OBJECTIVE: Hypercholesterolemia is an early risk factor for Alzheimer's disease. Low-density lipoprotein (LDL) receptors might be involved in this disorder. Our objective was to determine the risk of mild cognitive impairment in a population of patients with heterozygous familial hypercholesterolemia, a condition involving LDL receptor dysfunction and lifelong hypercholesterolemia. METHODS: By using a cohort study design, patients with familial hypercholesterolemia (N=47) meeting inclusion criteria and comparison patients without familial hypercholesterolemia (N=70) were consecutively selected from academic specialty and primary care clinics, respectively. All patients were older than 50 years. Those with disorders that could affect cognition, including history of stroke or transient ischemic attacks, were excluded from both groups. Thirteen standardized neuropsychologic tests were performed in all subjects. Mutational analysis was performed in patients with familial hypercholesterolemia, and brain imaging was obtained in those with familial hypercholesterolemia and mild cognitive impairment. RESULTS: Patients with familial hypercholesterolemia showed a high incidence of mild cognitive impairment compared with those without familial hypercholesterolemia (21.3% vs 2.9%; P=.00). This diagnosis was unrelated to structural pathology or white matter disease. There were significant differences, independent of apolipoprotein E4 or E2 status, between those with familial hypercholesterolemia and those with no familial hypercholesterolemia in several cognitive measures, all in the direction of worse performance for those with familial hypercholesterolemia. CONCLUSION: Because prior studies have shown that older patients with sporadic hypercholesterolemia do not show a higher incidence of mild cognitive impairment, the findings presented suggest that early exposure to elevated cholesterol or LDL receptor dysfunction may be risk factors for mild cognitive impairment.","Cholesterol, LDL/blood;Cognition/physiology;Cognition Disorders/diagnosis/ epidemiology/etiology;Female;Follow-Up Studies;Humans;Hyperlipoproteinemia Type II/blood/ complications/epidemiology;Incidence;Magnetic Resonance Imaging;Male;Middle Aged;Receptors, Lipoprotein/blood;Retrospective Studies;Risk Factors;Spain/epidemiology","Zambon, D.;Quintana, M.;Mata, P.;Alonso, R.;Benavent, J.;Cruz-Sanchez, F.;Gich, J.;Pocovi, M.;Civeira, F.;Capurro, S.;Bachman, D.;Sambamurti, K.;Nicholas, J.;Pappolla, M. A.",2010,Mar,10.1016/j.amjmed.2009.08.015,0,
113,Seed Location Impacts Whole-Brain Structural Network Comparisons between Healthy Elderly and Individuals with Alzheimer's Disease,"Whole-brain networks derived from diffusion tensor imaging (DTI) data require the identification of seed and target regions of interest (ROIs) to assess connectivity patterns. This study investigated how initiating tracts from gray matter (GM) or white matter (WM) seed ROIs impacts (1) structural networks constructed from DTI data from healthy elderly (control) and individuals with Alzheimer's disease (AD) and (2) between-group comparisons using these networks. DTI datasets were obtained from the Alzheimer's disease Neuroimaging Initiative database. Deterministic tractography was used to build two whole-brain networks for each subject; one in which tracts were initiated from WM ROIs and another in which they were initiated from GM ROIs. With respect to the first goal, in both groups, WM-seeded networks had approximately 400 more connections and stronger connections (as measured by number of streamlines per connection) than GM-seeded networks, but shared 94% of the connections found in the GM-seed networks. With respect to the second goal, between-group comparisons revealed a stronger subnetwork (as measured by number of streamlines per connection) in controls compared to AD using both WM-seeded and GM-seeded networks. The comparison using WM-seeded networks produced a larger (i.e., a greater number of connections) and more significant subnetwork in controls versus AD. Global, local, and nodal efficiency were greater in controls compared to AD, and between-group comparisons of these measures using WM-seeded networks had larger effect sizes than those using GM-seeded networks. These findings affirm that seed location significantly affects the ability to detect between-group differences in structural networks.",Alzheimer's disease;Dti;Mri;diffusion;graph theory;structural networks,"Zajac, L.;Koo, B. B.;Bauer, C. M.;Killiany, R.;Behalf Of The Alzheimer's Disease Neuroimaging, Initiative",2017,Apr 6,,0,
114,Vascular risk factors and white matter hyperintense lesions in Alzheimer's disease,"INTRODUCTION: Cerebrovascular injury and amyloid β deposition are associated with cognitive impairment. The relationship of these factors in Alzheimer's disease (AD) has been studied in other populations. OBJECTIVE: To describe the frequency of white matter hyperintensities using magnetic resonance imaging (MRI) in patients with AD. METHODS: In this retrospective, observational study we reviewed records of patients with diagnosis of dementia. We included in the analysis 35 patients with clinical classification criteria for probable AD, having examination by means of MRI. RESULTS: Mean age was 79.3 ó 6.5 years; 63% (n = 22) were female, the average years of schooling was 9.9 ó 6.4. The mean MMSE score was 20.4 ó 6.9. The prevalence of vascular risk factors at diagnosis of dementia was as follows: dyslipidemia 43%, smoking 43%, hypertension 34%, coronary artery disease 14% and cerebrovascular disease 2.8%. A 88.5% had white matter hyperintense lesions, almost a half with Fazekas 1 (48.6%). CONCLUSIONS: These findings support the theory of a vascular mechanism in EA or the existence of a single heterogeneous entity: mixed dementia.",,"Zaira, M. L.;Jazmín, P. L. T.;Gloria, A. N. S.;José, M. A. A.",2013,May-June,,0,
115,Structural and microstructral imaging of the brain in alcohol use disorders,"Magnetic resonance imaging (MRI), by enabling rigorous in vivo study of the longitudinal, dynamic course of alcoholism through periods of drinking, sobriety, and relapse, has enabled characterization of the effects of chronic alcoholism on the brain in the human condition. Importantly, MRI has distinguished alcohol-related brain effects that are permanent versus those that are reversible with abstinence. In support of postmortem neuropathologic studies showing degeneration of white matter, MRI has shown a specific vulnerability of brain white matter to chronic alcohol exposure by demonstrating white-matter volume deficits, yet not leaving selective gray-matter structures unscathed. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. This review focuses on MRI and DTI findings in common concomitants of alcoholism, including Wernicke's encephalopathy, Korsakoff's syndrome, hepatic encephalopathy, central pontine myelinolysis, alcoholic cerebellar degeneration, alcoholic dementia, and Marchiafava-Bignami disease as a framework for findings in so-called ""uncomplicated alcoholism,"" and also covers findings in abstinence and relapse.",,"Zahr, N. M.",2014,,10.1016/b978-0-444-62619-6.00017-3,0,
116,"Structural MRI Predictors of Late-Life Cognition Differ Across African Americans, Hispanics, and Whites","BACKGROUND: Structural magnetic resonance imaging (MRI) provides key biomarkers to predict onset and track progression of Alzheimer's disease (AD). However, most published reports of relationships between MRI variables and cognition in older adults include racially, ethnically, and socioeconomically homogenous samples. Racial/ethnic differences in MRI variables and cognitive performance, as well as health, socioeconomic status and psychological factors, raise the possibility that brain-behavior relationships may be stronger or weaker in different groups. The current study tested whether MRI predictors of cognition differ in African Americans and Hispanics, compared with non-Hispanic Whites. METHODS: Participants were 638 non-demented older adults (29% non-Hispanic White, 36% African American, 35% Hispanic) in the Washington Heights-Inwood Columbia Aging Project. Composite scores of memory, language, speed/executive functioning, and visuospatial function were derived from a neuropsychological battery. Hippocampal volume, regional cortical thickness, infarcts, and white matter hyperintensity (WMH) volumes were quantified with FreeSurfer and in-house developed procedures. Multiple-group regression analysis, in which each cognitive composite score was regressed onto MRI variables, demographics, and cardiovascular health, tested which paths differed across groups. RESULTS: Larger WMH volume was associated with worse language and speed/executive functioning among African Americans, but not among non-Hispanic Whites. Larger hippocampal volume was more strongly associated with better memory among non-Hispanic Whites compared with Hispanics. Cortical thickness and infarcts were similarly associated with cognition across groups. CONCLUSION: The main finding of this study was that certain MRI predictors of cognition differed across racial/ethnic groups. These results highlight the critical need for more diverse samples in the study of cognitive aging, as the type and relation of neurobiological substrates of cognitive functioning may be different for different groups.","African Americans/ psychology;Aged;Aged, 80 and over;Aging/ pathology/ psychology;Brain/ pathology;Cognition;European Continental Ancestry Group/ psychology;Female;Hispanic Americans/ psychology;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;New York City/epidemiology;Organ Size;Prospective Studies;Regression Analysis","Zahodne, L. B.;Manly, J. J.;Narkhede, A.;Griffith, E. Y.;DeCarli, C.;Schupf, N. S.;Mayeux, R.;Brickman, A. M.",2015,,,0,
117,Quantifying cognitive reserve in older adults by decomposing episodic memory variance: replication and extension,"The theory of cognitive reserve attempts to explain why some individuals are more resilient to age-related brain pathology. Efforts to explore reserve have been hindered by measurement difficulties. Reed et al. (2010) proposed quantifying reserve as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). This residual variance represents the discrepancy between an individual's predicted and actual memory performance. The goals of the present study were to extend these methods to a larger, community-based sample and to investigate whether the residual reserve variable is explained by age, predicts longitudinal changes in language, and predicts dementia conversion independent of age. Results support this operational measure of reserve. The residual reserve variable was associated with higher reading ability, lower likelihood of meeting criteria for mild cognitive impairment, lower odds of dementia conversion in dependent of age, and less decline in language abilities over 3 years. Finally, the residual reserve variable moderated the negative impact of memory variance explained by brain pathology on language decline. This method has the potential to facilitate research on the mechanisms of cognitive reserve and the efficacy of interventions designed to impart reserve.","Age Factors;Aged;Aged, 80 and over;Brain/*pathology;Cognitive Reserve/*physiology;Dementia/pathology/*physiopathology;Female;Humans;Language;Longitudinal Studies;Magnetic Resonance Imaging;Male;*Memory, Episodic;Mild Cognitive Impairment/pathology/physiopathology;Neuropsychological Tests;Psychiatric Status Rating Scales;Reading;Residence Characteristics","Zahodne, L. B.;Manly, J. J.;Brickman, A. M.;Siedlecki, K. L.;Decarli, C.;Stern, Y.",2013,Sep,10.1017/s1355617713000738,0,
118,Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application,"Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point.",,"Zahodne, L. B.;Manly, J. J.;Brickman, A. M.;Narkhede, A.;Griffith, E. Y.;Guzman, V. A.;Schupf, N.;Stern, Y.",2015,Oct,10.1016/j.neuropsychologia.2015.09.009,0,
119,A case of Alzheimer's disease with extensive focal white matter changes,The case of a patient is reported who suffered from disturbed concentration and memory and constructive apraxia. She had only mild neuropsychological deficits at the first examination. T2-weighted MRI presented extensive focal white matter changes. A brain biopsy showed changes typical for Alzheimer's disease (AD). The extent of the white matter lesions was surprising compared to the mild clinical signs she had. This case confirms that AD may result in prominent white matter disease caused by incomplete infarction or demyelination.,adult;Alzheimer disease;amnesia;apraxia;article;brain biopsy;brain injury;case report;concentration loss;female;human;infarction;neurologic examination;nuclear magnetic resonance imaging;priority journal;white matter,"Zahner, B.;Lang, C. J. G.;Engelhardt, A.;Thierauf, P.;Neundorfer, B.",1995,,,0,
120,Apolipoprotein epsilon 4 allele modifies waist-to-hip ratio effects on cognition and brain structure,"BACKGROUND: This study aimed to determine whether relationships between obesity, as measured by waist-to-hip ratio (WHR), and cognition and brain structure were modified by the apolipoprotein epsilon 4 allele (apoE4). METHODS: The sample included 1969 stroke- and dementia-free participants from the Framingham Offspring Cohort who underwent neuropsychological (NP) testing and structural magnetic resonance imaging (MRI) between 1999 and 2002. WHR was categorized into sex-specific quartiles with those in Q4 representing central obesity. Multivariate linear regression estimated the relationships between Q4-WHR, cognitive, and MRI measures; interaction terms examined modification of these relationships by the presence of apoE4. All analyses were cross sectional. RESULTS: ApoE4 status significantly modified a number of associations. Specifically, we observed a significant negative relationship between Q4-WHR and a measure of executive function in the apoE4(+) group but not in the apoE4(-) group. Similarly, we observed a stronger negative relationship between Q4-WHR and a measure of memory function for those in the apoE4(+) group compared to those in the apoE4(-) group. In addition, apoE4 status modified the relationship between Q4-WHR and 2 measures of structural brain integrity. First, a paradoxical finding of a negative association between WHR and frontal brain volume that was significant only for those in the apoE4(-) group, and a second finding that WHR was significantly associated with greater white matter hyperintensity volume only in the apoE4(+) group. CONCLUSIONS: These findings suggest that associations between central adiposity and both neuropsychological performance and underlying brain structure are highly complex and must be considered in the context of possible modifying genetic influences.",Adult;Aged;Alleles;Alzheimer Disease/epidemiology/genetics;Apolipoprotein E4/ genetics;Brain/anatomy & histology/ physiology;Cognition/ physiology;Cross-Sectional Studies;Executive Function/physiology;Female;Humans;Linear Models;Magnetic Resonance Imaging;Male;Metabolic Syndrome X/epidemiology/genetics;Middle Aged;Multivariate Analysis;Obesity/epidemiology/ genetics;Risk Factors;Waist-Hip Ratio/ statistics & numerical data,"Zade, D.;Beiser, A.;McGlinchey, R.;Au, R.;Seshadri, S.;Palumbo, C.;Wolf, P. A.;DeCarli, C.;Milberg, W.",2013,Feb,10.1016/j.jstrokecerebrovasdis.2011.06.020,0,
121,A Rare Cause of Hearing Loss: Susac Syndrome,"Susac's syndrome is a rare autoimmune disease, which is characterized by microangiopathic changes that affects the brain, retina, and cochlea. It is mainly characterized by asymptomatic cerebral infarctions, low-and mid-frequency sensorineural hearing loss, and bilateral distal retinal artery occlusions. Otolaryngologists should be familiar with Susac's syndrome because hearing loss may be the initial presenting symptom. The recommended treatment options vary from antithrombotic to immunomodulatory drugs. Although in its early stage, remission from the disease or self-limiting clinical course may be observed. Residual disabilities such as blindness, deafness, and dementia may also be presented in its late stages. Awareness of the condition and suspicion in selected patients will provide early diagnosis and treatment, which are both important to prevent the development of severe sequelae.",glucocorticoid;methylprednisolone;angiography;case report;female;perception deafness;human;laser coagulation;neurologic examination;nuclear magnetic resonance imaging;pathophysiology;procedures;retina vasculitis;Susac syndrome;treatment outcome;young adult,"Yurtsever, B.;Çabalar, M.;Kaya, H.;Tuğcu, B.;Yazıcı, Z. M.;Yayla, V.",2015,,,0,
122,Trousseau's Syndrome Caused by Intrahepatic Cholangiocarcinoma: An Autopsy Case Report and Literature Review,"An autopsy case report of Trousseau's syndrome caused by intrahepatic cholangiocarcinoma is presented, and seven previously reported cases are reviewed. A 73-year-old woman experiencing light-headedness and dementia of unknown cause for 6 months developed severe hypotonia. A hypointense lesion compatible with acute cerebral infarction was detected by magnetic resonance imaging. Abdominal computed tomography revealed an ill-defined large liver mass in the right lobe. The mass was not further investigated because of the patient's poor condition. She died of multiple organ failure, and an autopsy was conducted. Postmortem examination revealed intrahepatic cholangiocarcinoma, fibrous vegetations on the mitral valves and multiple thromboemboli in the cerebrum, spleen and rectum. Trousseau's syndrome is defined as an idiopathic thromboembolism in patients with undiagnosed or concomitantly diagnosed malignancy. This syndrome is encountered frequently in patients with mucin-producing carcinomas, while the incidence in patients with intrahepatic cholangiocarcinoma is uncommon. We found that tissue factor and mucin tumor marker (CA19-9, CA15-3 and CA-125) expression in cancer cells may be involved in the pathogenesis of thromboembolism. A patient with unexplained thromboembolism may have occult visceral malignancy; thus, mucin tumor markers may indicate the origin of a mucin-producing carcinoma, and postmortem examination may play an important role in revealing the hidden malignancy.",,"Yuri, T.;Kato, K.;Hirohara, Y.;Kinoshita, Y.;Emoto, Y.;Yuki, M.;Yoshizawa, K.;Tsubura, A.",2014,May,10.1159/000363689,0,
123,Centiloid method evaluation for amyloid PET of subcortical vascular dementia,"Reference region selection is important for proper amyloid PET analysis, especially in subcortical vascular dementia (SVaD) patients. We investigated reference region differences between SVaD and Alzheimer's disease (AD) using Centiloid scores. In 57 [C-11] Pittsburgh compound B (PiB) positive (+) AD and 23 PiB (+) SVaD patients, we assessed standardized PiB uptake and Centiloid scores in disease-specific cortical regions, with several reference regions: cerebellar gray (CG), whole cerebellum (WC), WC with brainstem (WC + B), pons, and white matter (WM). We calculated disease group differences from young controls (YC) and YC variance according to reference region. SVaD patients showed large effect sizes (Cohen's d > 0.8) using all reference regions. WM and pons showed larger YC variances than other regions. Findings were similar for AD patients. CG, WC, and WC + B, but not WM or pons, are reliable reference regions for amyloid imaging analysis in SVaD.",,"Yun, H. J.;Moon, S. H.;Kim, H. J.;Lockhart, S. N.;Choe, Y. S.;Lee, K. H.;Na, D. L.;Lee, J. M.;Seo, S. W.",2017,Nov 24,,0,
124,Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response,"BACKGROUND: Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from non-responders and healthy controls. METHODS: Participants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate gray matter and associated white matter tracts. RESULTS: 35.5% of depressed patients suffered from apathy. This declined to 15.6% (p<0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. LIMITATIONS: Modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner CONCLUSIONS: While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior.","Aged;Aged, 80 and over;Anisotropy;Antidepressive Agents, Second-Generation/ therapeutic use;Apathy;Citalopram/ therapeutic use;Depression/ drug therapy/ pathology/psychology;Depressive Disorder, Major/ drug therapy/ pathology/psychology;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Prevalence;Serotonin Uptake Inhibitors/ therapeutic use;Single-Blind Method;White Matter/pathology","Yuen, G. S.;Gunning, F. M.;Woods, E.;Klimstra, S. A.;Hoptman, M. J.;Alexopoulos, G. S.",2014,Sep,10.1016/j.jad.2014.05.008,0,
125,Pathological changes of vessels in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Objectives: To evaluate the vascular pathological changes in 4 probands from different CADASIL families. Methods: Sural nerve biopsies were performed in 4 probands, who had an onset of disease in an age of 38-44 years old and had the main sympotoms of recurrent stroke and dementia The diagnosis was confirmed by MRI findings and genetic results of Notch3 gene analyses in all probands. The sural biopsy specimens, including 4 patients and 6 non-CADASIL controls, were examined under light and electron microscopes. Results: The vascular pathological features in sural nerve of 4 CADASIL patients were: (1) without marked histological changes in vessel wall (Case 1 and 4); (2) atrophy of medial smooth muscle fibers of arterioles (Case 3) with thickening of arteriole intima, occasionally with perivascular infiltrate of lymphocyte and thickening of capillary basal lamina and micro-arteriole adventitia; (3) hypertrophy of medial smooth muscle fibers of arterioles (Case 2) with thickening of large arteriole intima and small arteriole adventitia. In all probands, GOM was noted in the basal lamina of vascular smooth muscle cells, more common affecting the arterioles and few, the capilaries and veins. Mild thickening of arteriole intima was observed in 2 of 6 controls. The media was unremarkable in all controls. Conclusions: The smooth muscle cells in arterioles with large caliber were involved more prominently. Therefore CADASIL should be an angiomyopathy. It might be considered as a goal to observe arteriole in diagnostic examination in disease. The vascular pathological changes should be varied markedly among different patients. The relationship among the extra-cerebral vascular changes, the symptoms and the Notch3 gene mutations need to be determined in the further.",adult;adventitia;arteriole;article;basement membrane;brain blood vessel;brain capillary;CADASIL;case report;clinical feature;dementia;diagnostic imaging;electron microscopy;female;gene;gene mutation;genetic analysis;human;human cell;human tissue;intima;lymphocytic infiltration;male;microscopy;muscle atrophy;muscle hypertrophy;nerve biopsy;notch3 gene;nuclear magnetic resonance imaging;onset age;recurrent disease;smooth muscle fiber;cerebrovascular accident;sural nerve;vascular disease;vascular smooth muscle,"Yuan, Y.;Wang, Z. X.;Zhang, W.;Lü, H.;Niu, X. Y.;Zhang, Z.",2005,,,0,
126,Non-Gaussian diffusion alterations on diffusion kurtosis imaging in patients with early Alzheimer's disease,"OBJECTIVE: To evaluate non-Gaussian diffusion changes of the whole-brain and its correlation with cognitive performance in patients with early Alzheimer's disease (AD), using diffusion kurtosis imaging (DKI). METHODS: Twenty-six patients with early AD and twenty-six normal controls underwent diffusion imaging. Seven parametric maps were calculated from multiple b-value diffusion data, including mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). Voxel-based analyses were performed to evaluate the group difference between the AD patients and normal controls. Then correlation between the diffusion parameters (MK, FA and MD) and cognitive performance were analyzed in AD patients. RESULTS: For AD patients, increased MD, AxD and RD were found in white matter (WM), including the genu of corpus callosum, bilateral cingulate bundle, bilateral temporal and frontal WM, and were also found in gray matter (GM), including the bilateral temporal GM, parahippocampal gyrus, hippocampus, cingulate gyrus, thalamus, and amygdala. These regions were partially overlapped with those showing decreased FA, MK, AK and RK. However, only kurtosis indices could detect the significant differences in the lentiform nucleus between AD patients and health control. DKI indices in AD patients significantly correlated with the clinical scores in genu of CC, cingulate bundle, temporal and frontal lobe, while the voxel number showing significant correlation with MK was more than that with FA and MD. CONCLUSIONS: Early AD patients already have microstructural changes in both WM and GM. DKI can provide supplementary information in reflecting these changes and may be sensitive in diagnosing early AD.",,"Yuan, L.;Sun, M.;Chen, Y.;Long, M.;Zhao, X.;Yin, J.;Yan, X.;Ji, D.;Ni, H.",2016,Mar 11,10.1016/j.neulet.2016.01.021,0,
127,Non-gaussian diffusion characteristics of early Alzheimer disease: a diffusion kurtosis imaging study,"Objective: To evaluate non-Gaussian diffusion features of the white and gray matter microstructrual change in early Alzheimer disease (AD) patients using diffusion kurtosis imaging (DKI). Methods: Conventional and diffusion MR sequences were conducted in 22 AD patients (AD group) and 20 normal controls (control group). Seven indexes including mean kurtosis (MK), axial kurtosis (K<inf>//</inf>), radial kurtosis (K<inf>⊥</inf>), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (D<inf>//</inf>), and radial diffusivity (D<inf>⊥</inf>) were calculated by diffusion kurtosis estimator (DKE) software and the corresponding maps were obtained. Then region of interests (ROI) were put on the predetermined structures, including splenium of the corpus callosum (SCC), posterior part of the cingulate bundle (PCB), frontal and temporal white matter (FWM, TWM), thalamus (T) and hippocampus (H). Indexes of all the ROI were calculated and the two sample t-tests were underwent between the AD and control groups with the SPSS17.0 software. In AD group, Pearson correlation analyses were also performed between the mini-mental state examination (MMSE) scores and indexes of the ROl which had significant difference between the groups. Results: In the white matter regions, MD, D<inf>//</inf> and D<inf>⊥</inf> in many regions of AD group were increased significantly than the control group, and the differences were statistically significant. MD and D, showed more abnormalities, including the SCC, PCB, and FWM. Meanwhile, MK, K<inf>//</inf> and K<inf>⊥</inf> in many regions of AD were decreased, and the differences were statistically significant. K<inf>⊥</inf> showed more abnormalities, including the SCC, FWM and TWM. In the gray matter regions, MD, D<inf>//</inf> and D<inf>⊥</inf> of hippocampal of the AD group were all increased than the control group. However, it showed that MK and K<inf>⊥</inf> of the thalamus in AD group were 0.99±0.10, 1.00±0.11, respectively, and both increased than the control group (the value of MK and K<inf>⊥</inf> were 0.90±0.06, 0.90±0.07, respectively), and the differences were statistically significant (t values was 3.31, 3.57 respectively, and both P values were <0.01). The indexes of different ROI had correlations with the MMSK scores. There were more regions in kurtosis indexes correlated with the MMSE scores than the diffusion indexes. The strongest correlation among the analyses was MK of the SCC (r=0.73, P<0.05). Conclusions: This study based on DKI found the complex alterations aroused by microstructural changes were not only in the white matter but also the gray matter of the AD patients, especially the increased kurtosis of the thalamus, and this suggested that the microstructural complexity of it was increased. Moreover, it also suggested that indexes of DKI had varied sensitivity in detecting different diffusion alterations.",Alzheimer disease;article;clinical article;controlled study;corpus callosum;data analysis software;diffusion kurtosis imaging;diffusion weighted imaging;fractional anisotropy;gray matter;hippocampus;human;image analysis;Mini Mental State Examination;thalamus;white matter,"Yuan, L.;Sun, M.;Chen, Y.;Long, M.;Yin, J.;Ni, H.",2015,,10.3760/cma.j.issn.1005-1201.2015.08.002,0,128
128,Non-gaussian diffusion characteristics of early Alzheimer disease: a diffusion kurtosis imaging study,"Objective: To evaluate non-Gaussian diffusion features of the white and gray matter microstructrual change in early Alzheimer disease (AD) patients using diffusion kurtosis imaging (DKI). Methods: Conventional and diffusion MR sequences were conducted in 22 AD patients (AD group) and 20 normal controls (control group). Seven indexes including mean kurtosis (MK), axial kurtosis (K<inf>//</inf>), radial kurtosis (K<inf>⊥</inf>), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (D<inf>//</inf>), and radial diffusivity (D<inf>⊥</inf>) were calculated by diffusion kurtosis estimator (DKE) software and the corresponding maps were obtained. Then region of interests (ROI) were put on the predetermined structures, including splenium of the corpus callosum (SCC), posterior part of the cingulate bundle (PCB), frontal and temporal white matter (FWM, TWM), thalamus (T) and hippocampus (H). Indexes of all the ROI were calculated and the two sample t-tests were underwent between the AD and control groups with the SPSS17.0 software. In",,"Yuan, L.;Sun, M.;Chen, Y.;Long, M.;Yin, J.;Ni, H.",2015,10,,0,
129,How does white matter microstructure differ between the vascular and amnestic mild cognitive impairment?,"Changes in white matter (WM) microstructure may relate to the pathophysiology of cognitive impairment. Whether WM microstructure differs in two common pre-dementia subtypes, vascular mild cognitive impairment (VaMCI) and amnestic mild cognitive impairment (aMCI), is largely unknown. This study included 28 VaMCI (12 men, age: 46 ~ 77 years) and 34 aMCI patients (14 men, age: 51 ~ 79 years). All patients underwent a battery of neuropsychological tests and structural and diffusion magnetic resonance imaging (MRI) scanning. WM microstructure was quantified using diffusion MRI parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). These parameters were compared between the two patient groups using tract-based spatial statistics (TBSS) after controlling for age, gender, and education. No significant differences in FA/MD/AxD/RD were observed between the VaMCI and aMCI groups, which suggests a similar pattern of WM microstructure in the early stage of cognitive impairment for different dementia types. However, the two groups exhibited significant differences in the relationship between FA and the Auditory Verbal Learning Test (AVLT), which were primarily located around the corona radiate and corpus callosum. Specifically, there were significant positive correlations (R = 0.64, P < 0.001) between the FA and AVLT in the VaMCI group, but the opposite trend was observed in the aMCI group (R = -0.34, P = 0.047). The differential relationship between WM and memory between VaMCI and aMCI indicates an independent neuropathology for specific memory deficits in different types of dementia.",Gerotarget;mild cognitive impairment;neuroimage,"Yu, Y.;Liang, X.;Yu, H.;Zhao, W.;Lu, Y.;Huang, Y.;Yin, C.;Gong, G.;Han, Y.",2017,Jan 03,,0,
130,[Age features of pure leukoaraiosis in non-demented outpatients],"To investigate the aging features of pure leukoaraiosis (LA) in non-demented outpatients. The outpatients with age older than 40 years, without taking cholesterol lowering and B vitamin medications and with mini-mental state examination more than 24 scores were selected from July 2008 to December. 2009 in Beijing Tiantan Hospital. LA was defined with MRI. Patients were classified into two groups i.e. LA group consisting of 138 patients with leukoaraiosis but without lacunar lesions and cortical infarcts and a control group consisting of 124 patients without any lesion in brain. Age and other vascular risk factors were also investigated. Age of the patients in the LA group was significantly higher than that in the control group (P<0.001). Multivariable logistic regression analysis showed that age was independently associated with pure LA (OR 1.080, 95%CI 1.042-1.120), after adjusting sex, vascular risk factors and presence of atherosclerosis in cervical arteries. If age-stratification was further considered, logistic regression analysis showed that OR (95%CI) for LA was 2.693 (95%CI 1.103-6.575) in a 60-69 year group and 13.527 (95%CI 3.319-55.131) in a ≥70 year group as compared with a 40-49 year group. Age is a determining risk factor for pure LA and patients with age older than 60 years are at high risk of LA.",adult;age distribution;article;factorial analysis;female;human;leukoaraiosis;male;middle aged;outpatient;risk factor;statistical model,"Yu, X. Y.;Wang, G. H.;Guan, X. T.;Liu, Y.;Wang, S. X.;Liu, Z. Z.;Wang, Y. J.",2010,,,0,
131,Coarse Classification to Region-Scalable Refining for White Matter Lesions Segmentation in Multi-Channel MRI,"Brain lesions, especially White Matter Lesions (WMLs) that mostly found on magnetic resonance images of elderly people, are not only associated with normal aging, but also with various geriatric disorders including cardiovascular diseases, vascular disease, psychiatric disorders and dementia. Quantitative analysis of WMLs in large clinical trials is crucial in scientific investigations of such neurological diseases as well as in studying aging processes. Exploiting the different appearances of WMLs in multiple modalities, we propose a novel coarse classification to region-scalable refining method to segment WMLs in Magnetic Resonance Imaging (MRI) sequences without user intervention. Specifically, a nonlinear voxel-wise classifier is trained based on intensity features extracted from multimodality MRI sequences, and tissues' probabilistic prior provided by partial volume estimate images in native space. By considering the prior that the WMLs almost exist in white matter, a rejection algorithm is then used to eliminate the false-positive labels from the initial coarse classification. To further segment precise lesions boundary and detect missing lesions, a region-scalable refining is finally employed to effectively segment the WMLs based on the previous initial contour. Compared with the manual segmentation results from an experienced neuroradiologist, the segmentations for real images of our proposal show desirable performances and high accuracy and provide competitive solution with stateof- the-art methods.",Active contour;nonlinear classifier;partial volume estimate;segmentation;white matter lesions,"Yu, R.;Xiao, L.;Wei, Z.",2017,,,0,132
132,Coarse Classification to Region-Scalable Refining for White Matter Lesions Segmentation in Multi-channel MRI,"Brain lesions, especially White Matter Lesions (WMLs) that mostly found on magnetic resonance images of elderly people, are not only associated with normal aging, but also with various geriatric disorders including cardiovascular diseases, vascular disease, psychiatric disorders and dementia. Quantitative analysis of WMLs in large clinical trials is crucial in scientific investigations of such neurological diseases as well as in studying aging processes. Exploiting the different appearances of WMLs in multiple modalities, we propose a novel coarse classification to region-scalable refining method to segment WMLs in Magnetic Resonance Imaging (MRI) sequences without user intervention. Specifically, a nonlinear voxel-wise classifier is trained based on intensity features extracted from multi-modality MRI sequences, and tissues' probabilistic prior provided by partial volume estimate images in native space. By considering the prior that the WMLs almost exist in white matter, a rejection algorithm is then used to eliminate the false-positive labels from the initial coarse classification. To further segment precise lesions boundary and detect missing lesions, a region-scalable refining is finally employed to effectively segment the WMLs based on the previous initial contour. Compared with the manual segmentation results from an experienced neuroradiologist, the segmentations for real images of our proposal show desirable performances and high accuracy and provide competitive solution with state-of-the-art methods.",,"Yu, R.;Xiao, L.;Wei, Z.",2016,Dec 20,,0,
133,Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia,"Alterations of the transverse relaxation rate, R2, measured using MRI, are observed in older persons with Alzheimer's (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R2 alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounting for neuropathologic indices of AD, cerebral infarcts, Lewy body disease, hippocampal sclerosis and transactive response DNA-binding protein 43. Data came from 567 post-mortem brains donated by participants in two cohort studies of aging and dementia. R2 was quantified using fast spin echo imaging. Voxelwise linear regression examined R2 alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R2 alterations were clustered into regions of interest (ROIs). Three R2 profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R2 alterations were observed throughout the hemisphere, most commonly in white matter. Of the distinct ROIs identified, the largest region encompassed large portions of white matter in all lobes. This ROI became smaller in size but remained largely intact after adjusting for AD and other neuropathologic indices. Further, R2 alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p < 0.0001). In conclusion, R2 alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work.",TAR DNA binding protein;aged;Alzheimer disease;article;autopsy;brain infarction;cohort analysis;controlled study;diagnostic accuracy;diagnostic test accuracy study;diffuse Lewy body disease;electron spin resonance;ex vivo study;female;hippocampal sclerosis;human;human tissue;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;radiological parameters;sensitivity and specificity;transverse relaxation rate;white matter,"Yu, L.;Dawe, R. J.;Buchman, A. S.;Boyle, P. A.;Schneider, J. A.;Arfanakis, K.;Bennett, D. A.",2017,,10.1016/j.bbr.2016.09.001,0,134
134,Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia,"Alterations of the transverse relaxation rate, R2, measured using MRI, are observed in older persons with Alzheimer's (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R2 alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounting for neuropathologic indices of AD, cerebral infarcts, Lewy body disease, hippocampal sclerosis and transactive response DNA-binding protein 43. Data came from 567 post-mortem brains donated by participants in two cohort studies of aging and dementia. R2 was quantified using fast spin echo imaging. Voxelwise linear regression examined R2 alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R2 alterations were clustered into regions of interest (ROIs). Three R2 profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R2 alterations were observed throughout the hemisphere, most commonly in white matter. Of the distinct ROIs identified, the largest region encompassed large portions of white matter in all lobes. This ROI became smaller in size but remained largely intact after adjusting for AD and other neuropathologic indices. Further, R2 alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p<0.0001). In conclusion, R2 alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work.",AD dementia;Age-related neuropathology;Ex vivo MRI;Transverse relaxation alterations,"Yu, L.;Dawe, R. J.;Buchman, A. S.;Boyle, P. A.;Schneider, J. A.;Arfanakis, K.;Bennett, D. A.",2016,Sep 3,10.1016/j.bbr.2016.09.001,0,
135,Cortico-striatal connectivity and cognition in normal aging: A combined DTI and resting state fMRI study,"Resting state fMRI studies have found that cognitive decline in aging is associated with alterations in functional connectivity of distributed neural systems in the brain. While functional connections have been shown to rely on the underlying structural connectivity, direct structural connections have been studied in only a few distributed cortical systems so far. It is well known that subcortical nuclei have structural connections to the entire cortex. We hypothesized that structural subcortico-cortical connections may provide integral routes for communication between cortical resting state networks, and that changes in the integrity of these connections have a role in cognitive aging. We combined anatomical MRI, diffusion tensor MRI, and resting state fMRI in 100 healthy elderly to identify fiber bundles connecting cortical resting state networks to subcortical nuclei. In identified tracts, white matter fiber bundle integrity measures were compared to composite cognitive measures on executive function, processing speed, and memory performance. The integrity (FA values) in selected fiber bundles correlated strongly with cognitive measures on executive function and processing speed. Correlation was most pronounced between executive function and fiber bundles connecting the putamen to the dorsal attention network (r = 0.73, p < 0.001). Our findings show that unique cortico-subcortical fiber bundles can be identified for a range of cortical resting state networks, and indicate that these connections play an important role in cortical resting state network communication and cognition. © 2010.",adult;aged;aging;article;attention;basal ganglion;brain cortex;brain function;brain mapping;cognition;controlled study;corpus striatum;diffusion tensor imaging;female;functional magnetic resonance imaging;human;human experiment;image analysis;male;memory;nerve cell network;nerve fiber;normal human;priority journal;putamen;rest;white matter,"Ystad, M.;Hodneland, E.;Adolfsdottir, S.;Haász, J.;Lundervold, A. J.;Eichele, T.;Lundervold, A.",2011,,,0,
136,Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathy related to a genetic defect of the notch 3 gene on chromosome 19. The purpose of this study was to evaluate lesion distribution and volume using MR imaging and to correlate the lesion volume with the neurologic and neuropsychological findings. METHODS: Twenty members of two families (14 with CADASIL as determined by linkage analysis, six healthy) were studied with MR imaging. Two observers evaluated the MR findings semiquantitatively and quantitatively. MR results were then correlated with neurologic and neuropsychological findings. RESULTS: A typical pattern of lesion distribution in patients with CADASIL was found: the frontal lobe was the site with the highest lesion load, followed by the temporal lobe and the insula. The total lesion volume on T1-weighted MR images correlated significantly with the degree of disability and the degree of impairment in neuropsychological functions (including attention, memory, and conceptual and visuospatial functions). CONCLUSION: In CADASIL patients, a common pattern of cerebral lesion distribution is found. The total T1 lesion volume is an important parameter to correlate with disability, as it may prove to be helpful in predicting the natural history of the disease.","Adult;Aged;Brain/ pathology;Brain Diseases/ diagnosis/ genetics/psychology;Cerebral Infarction/diagnosis/genetics/psychology;Cerebrovascular Disorders/diagnosis/genetics/psychology;Dementia, Multi-Infarct/genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination;Neuropsychological Tests","Yousry, T. A.;Seelos, K.;Mayer, M.;Bruning, R.;Uttner, I.;Dichgans, M.;Mammi, S.;Straube, A.;Mai, N.;Filippi, M.",1999,Jan,,0,
137,Nuclear magnetic resonance (NMR) imaging in white matter disease of the brain using spin-echo sequences,"Attention is drawn to the use of nuclear magnetic resonance (NMR) spin-echo sequences in the recognition of white matter disease of the brain. In 5 patients with multiple sclerosis, 8 lesions were seen with postcontrast x-ray computed tomography (CT) (37.5 g of iodine), 33 with inversion-recovery (IR) scans, and 47 with spin-echo (SE) scans. Partial volume effects were less of a diagnostic difficulty with SE scans than with IR scans. Extensive areas of abnormal white matter were seen with CT, IR, and SE scans in a patient with leucodystrophy associated with congenital muscular dystrophy. In a patient with adrenoleucodystrophy focal lesions were seen with CT, IR, and SE scans. In addition, loss of gray-white matter contrast was seen in both occipital lobes with IR scans. Extensive areas of white matter involvement were also seen in a case of Binswangers disease.","Adrenoleukodystrophy/diagnosis;Adult;Brain;Brain Diseases/ diagnosis/radiography;Child, Preschool;Dementia/diagnosis;Female;Humans;Magnetic Resonance Spectroscopy/ methods;Male;Middle Aged;Multiple Sclerosis/ diagnosis/radiography;Tomography, X-Ray Computed","Young, I. R.;Randell, C. P.;Kaplan, P. W.;James, A.;Bydder, G. M.;Steiner, R. E.",1983,Apr,,0,
138,First Report of Arg587Cys Mutation of Notch3 Gene in Two Chinese Families with CADASIL,Objective To explore Notch3 mutation sites of Chinese patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods Direct sequencing of all exons in Notch3 gene was performed on 12 unrelated suspected CADASIL cases from mainland China. Result A missense p.Arg587Cys (1759C>T) mutation in exon 11 was identified in 2 patients through genetic analysis. Conclusion Chinese patients with CADASIL of R587C mutation in exon 11 was firstly reported.,Notch3 receptor;adult;article;brain circulation;CADASIL;case report;Chinese;cognitive defect;computer assisted tomography;daily life activity;dizziness;exon;gene identification;gene mutation;gene sequence;genetic analysis;genetic screening;human;hypertension;male;memory disorder;middle aged;Mini Mental State Examination;missense mutation;mood disorder;neuroimaging;nuclear magnetic resonance imaging;priority journal;susceptibility weighted imaging;vertigo,"You, J.;Liao, S.;Zhang, F.;Ma, Z.;Li, G.",2017,,10.1016/j.jstrokecerebrovasdis.2016.09.014,0,
139,White matter in the older brain is more plastic than in the younger brain,"Visual perceptual learning (VPL) with younger subjects is associated with changes in functional activation of the early visual cortex. Although overall brain properties decline with age, it is unclear whether these declines are associated with visual perceptual learning. Here we use diffusion tensor imaging to test whether changes in white matter are involved in VPL for older adults. After training on a texture discrimination task for three daily sessions, both older and younger subjects show performance improvements. While the older subjects show significant changes in fractional anisotropy (FA) in the white matter beneath the early visual cortex after training, no significant change in FA is observed for younger subjects. These results suggest that the mechanism for VPL in older individuals is considerably different from that in younger individuals and that VPL of older individuals involves reorganization of white matter.",,"Yotsumoto, Y.;Chang, L. H.;Ni, R.;Pierce, R.;Andersen, G. J.;Watanabe, T.;Sasaki, Y.",2015,,,0,
140,Cortical damage in Alzheimer's disease estimation in medial and lateral aspects of the cerebrum using an improved mapping method based on diffusion-weighted magnetic resonance imaging,"RATIONALE AND OBJECTIVES: A method of estimating and mapping the cortical damage resulting from neurodegenerative diseases based on diffusion-weighted imaging was recently proposed. We improved on this method to visualize the cortical damage in Alzheimer's disease (AD) in the lateral and medial aspects of the cerebral hemispheres and to provide anatomic references. MATERIALS AND METHODS: Damage in the cerebral cortex was estimated based on diffusivity in the subcortical white matter according to a previously published method. A map of subcortical mean diffusivity (MD) was superimposed on the corresponding anatomic image so that the spatial extent of the abnormality could be anatomically localized. The right and left hemispheres were separated to evaluate the medial and lateral aspects of each hemisphere. This method was applied to 10 healthy subjects and 11 AD patients. MDs within 20 cortical regions were visually evaluated and statistically compared between AD and healthy subjects at a significance level of P < .01. RESULTS: In addition to the involvement of the lateral aspects of the bilateral parietal and temporal lobes and clear sparing of the bilateral pericentral regions that were previously reported, significant MD elevation was observed in the medial aspects of the right frontal, bilateral parietal, and right temporal lobes. The extent of MD abnormalities was easily identified by the background anatomic image. CONCLUSIONS: Results suggested that AD damage in the lateral and medial cerebral cortex can be visualized with an anatomic reference using our method.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain Mapping/ methods;Cerebrum/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Male;Middle Aged;Retrospective Studies;Statistics, Nonparametric","Yoshiura, T.;Noguchi, T.;Koga, H.;Ohyagi, Y.;Hiwatashi, A.;Togao, O.;Yamashita, K.;Kumazawa, S.;Mihara, F.;Honda, H.",2008,Feb,10.1016/j.acra.2007.10.008,0,
141,High b value diffusion-weighted imaging is more sensitive to white matter degeneration in Alzheimer's disease,"It has been reported that diffusion-weighted imaging (DWI) can detect white matter degeneration in the Alzheimer's disease (AD) brain. We hypothesized that imaging of the slow diffusion component using high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI, and therefore we studied the effects of high b value on lesion-to-normal contrast and contrast-to-noise ratio (CNR). Seven AD patients and seven age-matched normal subjects were studied with full-tensor DWI at three different b values (1000, 2000, and 4000 s/mm(2)) without changing echo time or diffusion time, and the mean diffusivities in the parietal and occipital regions were measured. Statistical analyses revealed that use of higher b values significantly improves both lesion-to-normal contrast and CNR. We concluded that high b value DWI is more sensitive to AD-related white matter degeneration than is conventional DWI.","Aged;Algorithms;Alzheimer Disease/ pathology;Axons/physiology;Brain/ pathology;Brain Mapping;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Degeneration/ pathology;Occipital Lobe/physiology;Parietal Lobe/pathology","Yoshiura, T.;Mihara, F.;Tanaka, A.;Ogomori, K.;Ohyagi, Y.;Taniwaki, T.;Yamada, T.;Yamasaki, T.;Ichimiya, A.;Kinukawa, N.;Kuwabara, Y.;Honda, H.",2003,Sep,,0,
142,Novel method to estimate and display cerebral cortical degeneration using diffusion-weighted magnetic resonance imaging,"Previous studies have shown that diffusion-weighted imaging (DWI) is useful for detecting microstructural degradation of neuronal tissue in neurodegenerative diseases. Mapping of cortical degeneration by DWI is potentially useful, but is extremely difficult, mainly because of the partial volume effect resulting from the surrounding cerebrospinal fluid (CSF). In this study a novel method to map and display the cortical damage in neurodegenerative diseases using DWI is proposed. Instead of measuring the cortical diffusivity, the diffusivity of white matter directly beneath the cortex, where neuronal fibers enter or exit the overlying cortex, was measured and mapped onto the cortical surface. The map was viewed in a form of three-dimensional (3D) rendering. Patients with Alzheimer's disease (AD) showed cortical damage in the temporal and parietal cortices, and a patient with frontotemporal dementia showed damage in the frontal lobe, consistent with the typical topographical distribution of histopathological cortical damage in each of these diseases. The results suggest that subcortical diffusivity closely reflects cortical damage, and that the current mapping technique is a promising tool for evaluating neurodegenerative diseases.","Adult;Aged;Alzheimer Disease/ pathology;Case-Control Studies;Cerebral Cortex/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Feasibility Studies;Female;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Male;Middle Aged","Yoshiura, T.;Mihara, F.;Tanaka, A.;Noguchi, T.;Togao, O.;Kuwabara, Y.;Honda, H.",2005,Aug,10.1002/mrm.20558,0,
143,Diffusion tensor in posterior cingulate gyrus: Correlation with cognitive decline in Alzheimer's disease,"To determine whether the diffusion abnormalities in brains with Alzheimer's disease (AD) correlate with disease severity, we studied 34 AD patients using diffusion tensor MRI. Mean diffusivity and fractional anisotropy (FA) as well as three eigenvalues (λ1, λ2, and λ3) of the diffusion tensor of the posterior cingulate white matter correlated with the Mini-Mental State Examination (MMSE) score. The mean diffusivity and the three eigenvalues showed significant correlation with the MMSE score. On the other hand, no significant correlation was seen between the FA and MMSE score. Our results suggested that mean diffusivity and the eigen-values, but not FA, reflect progression of AD-related histopathlogical changes in the posterior cingulate white matter and may be useful biological indices to monitor AD. © 2002 Lippincott Williams & Wilkins.",adult;aged;Alzheimer disease;article;cingulate gyrus;clinical article;cognitive defect;controlled study;correlation analysis;diffusion tensor imaging;disease severity;female;human;male;Mini Mental State Examination;priority journal;white matter,"Yoshiura, T.;Mihara, F.;Ogomori, K.;Tanaka, A.;Kaneko, K.;Masuda, K.",2002,,,0,
144,Mapping of Subcortical White Matter Abnormality in Alzheimer's Disease Using Diffusion-Weighted Magnetic Resonance Imaging,"Rationale and Objectives: White matter (WM) abnormality in Alzheimer's disease (AD) has been less well characterized than cortical damage. We studied the spatial distribution of the subcortical WM abnormality using diffusion-weighted magnetic resonance imaging (DWI). Materials and Methods: Twenty-one AD patients and seven healthy, elderly subjects were included. DWIs were obtained using a cerebrospinal fluid (CSF)-nulled pulse sequence to reduce the partial volume contamination of CSF signal. Diffusivity in the subcortical WM voxels was mapped onto the cortical surface using original software so that the spatial distribution of subcortical WM damage, which was visualized as an area of increased diffusivity, could be viewed in a three-dimensional map. The damages in the lateral surface of the bilateral cerebral hemispheres were visually evaluated, and severities of the damages in five brain regions were compared with each other. In addition, the severity of the damage in each region was correlated with patient's mini-mental state examination (MMSE) score. Results: In both hemispheres, clear sparing of the pericentral regions and predominant involvement of the parietal and temporal regions were revealed with statistical significance (P < .05, respectively). Marginal correlation (P < .05 uncorrected for multiple comparisons) was observed between the damage severity in the bilateral frontal and right temporal regions and patient's MMSE score. Conclusion: We demonstrated a subcortical WM abnormality over the parietal and temporal regions with clear sparing of the pericentral region using our mapping method, which supported the hypothesis that the subcortical WM abnormality in AD originates in Wallerian degeneration. © 2006 AUR.",,"Yoshiura, T.;Mihara, F.;Koga, H.;Ohyagi, Y.;Noguchi, T.;Togao, O.;Ogomori, K.;Miyoshi, K.;Yamasaki, T.;Kaneko, K.;Ichimiya, A.;Kanba, S.;Honda, H.",2006,December,,0,
145,Cerebral white matter degeneration in frontotemporal dementia detected by diffusion-weighted magnetic resonance imaging,"RATIONALE AND OBJECTIVE: Brain tissue damage in frontotemporal dementia (FTD) has never been systematically studied using diffusion-weighted imaging (DWI). We studied FTD patients using DWI to determine whether microstructural changes in white matter can be detected in vivo. MATERIALS AND METHODS: Thirteen FTD patients and 15 aged healthy subjects were studied. Mean diffusivity (MD) abnormalities in 28 white matter regions were visually evaluated. In addition, MD values in 10 white matter regions relative to that in the ipsilateral postcentral gyrus were measured. The results were compared between healthy subjects and FTD patients. RESULTS: The visual rating resulted in a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, right orbitofrontal gyrus, bilateral anterior temporal lobes, and left middle temporal lobe (P < .01, respectively). Relative MD comparison revealed a significant MD elevation in FTD patients in the bilateral high superior frontal gyri, bilateral orbitofrontal gyri, and bilateral anterior temporal lobes (P < .05 after Bonferroni correction, respectively). CONCLUSION: Our results demonstrated white matter MD abnormalities in FTD patients. It was suggested that the observed white matter MD abnormalities are secondary to damage in the overlying cortex.","Aged;Aged, 80 and over;Case-Control Studies;Cerebral Cortex/ pathology;Dementia/ diagnosis/epidemiology/pathology;Diffusion Magnetic Resonance Imaging;Female;Frontal Lobe/pathology;Humans;Image Processing, Computer-Assisted;Japan/epidemiology;Male;Middle Aged;Observer Variation;Occipital Lobe/pathology;Parietal Lobe/pathology;Reproducibility of Results;Research Design;Retrospective Studies;Temporal Lobe/pathology","Yoshiura, T.;Mihara, F.;Koga, H.;Noguchi, T.;Togao, O.;Ohyagi, Y.;Ogomori, K.;Ichimiya, A.;Kanba, S.;Honda, H.",2006,Nov,10.1016/j.acra.2006.08.009,0,
146,Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study,"We followed 828 nondemented residents of Hisayama Town, Kyushu, Japan, aged 65 years or older (88.3% of the elderly population) for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general Japanese population. Only two subjects were lost to the follow-up, during which period 103 subjects developed dementia. Morphologic examination of the brains of 89 subjects (86.4%) was made by autopsy or CT. We made the initial diagnosis of dementia based on the DSM-III-R criteria, with the diagnoses of vascular dementia (VD) being based on the NINDS-AIREN criteria and Alzheimer's disease (AD) on the NINCDS-ADRDA criteria. The incidence of VD and AD increased with age for both sexes. The age-adjusted total incidence (per 1,000 person-years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates for VD were 12.2 for men and 9.0 for women, and for AD, 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology we examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant independent risk factors for the occurrence of VD. In contrast, age and a low score on Hasegawa's dementia scale were significant risk factors for AD, and physical activity was a significant preventive factor for AD.(ABSTRACT TRUNCATED AT 250 WORDS)","Aged;Aged, 80 and over;Alzheimer Disease/complications/*epidemiology;Cerebrovascular Disorders/complications/epidemiology;Dementia, Vascular/complications/*epidemiology;Female;Humans;Japan/epidemiology;Male;Risk Factors","Yoshitake, T.;Kiyohara, Y.;Kato, I.;Ohmura, T.;Iwamoto, H.;Nakayama, K.;Ohmori, S.;Nomiyama, K.;Kawano, H.;Ueda, K.;et al.",1995,Jun,,0,
147,"Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD","OBJECTIVE: To analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). METHODS: We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons. RESULTS: Total WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk. CONCLUSIONS: Differences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Cognition Disorders/ pathology;Female;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reference Values","Yoshita, M.;Fletcher, E.;Harvey, D.;Ortega, M.;Martinez, O.;Mungas, D. M.;Reed, B. R.;DeCarli, C. S.",2006,Dec 26,10.1212/01.wnl.0000249119.95747.1f,0,
148,Current concepts of analysis of cerebral white matter hyperintensities on magnetic resonance imaging,"Cerebrovascular disease is common and associated with cognitive deficits and increased risk for dementia. Until recently, only limited attention has focused on advances in imaging techniques to better define and quantify the spectrum of asymptomatic cerebrovascular disease commonly seen on magnetic resonance imaging, such as abnormal white matter signals. Abnormal signals in cerebral white matter, although nonspecific, are increased in prevalence and severity in association with aging and cerebrovascular risk factors among older individuals. The ubiquitous occurrence of these abnormal white matter signals commonly referred to as white matter hyperintensities (WMHs) and the association with cerebrovascular risk and cognitive impairment among older individuals make scientific evaluation of WMHs an important and much needed avenue of research. In this section, we review current methods of WMH analysis. Strengths and limitation of both quantitative and qualitative methods are discussed initially, followed by a brief review of current magnetic resonance imaging segmentation and mapping techniques that make it possible to assess the anatomical location of WMHs. We conclude by discussing future analytic methods designed to better understand the pathophysiology and cognitive consequences of WMHs. © 2005 Lippincott Williams & Wilkins, Inc.",,"Yoshita, M.;Fletcher, E.;DeCarli, C.",2005,December,,0,
149,A case of spongiform encephalopathy with ataxia and amyloid plaques,"A 63-year-old man was admitted to our hospital because of gait disturbance. His daughter died of the same disorder at age 29. In 1974, at age 59, the patient noticed mild recent memory disturbance and clumsiness in handwriting. In 1976, his gait was markedly unstable, but he could walk without assistance, and his speech became dysarthric. In 1977, he was unable to walk without assistance. From Jan. 9, 1978, through Feb. 14, 1978, he was hospitalized. Neurological examination revealed an ataxic gait and scanning speech. Deep tendon reflexes of the upper extremites and ankle jerks were normal, but knee jerks were absent. Pathological reflexes were not elicited. Both superficial and deep sensations were normal. He was alert and showed no overt dementia. Laboratory data including CSF, EEG and brain CT were normal except positive TPHA in serum. Therefore, he was followed up with the diagnosis of spinocerebellar degeneration. In 1979, he developed a limb ataxia. In 1980, he became very irritable and was easily excited. He gradually developed dementia and urinary incontinence. In 1981, his illness progressed to an akinetic mutism and he died of pneumonia on July 19, 1981. Myoclonus and periodic synchronous discharges in EEG were not observed until his death. The brain was 1,075 g in weight after formalin fixation and the cerebrum was generally soft. The gyri showed no evidence of abnormalities or atrophy, while the cereburllum and brain stem, especially the pons, were atrophic. The arterial and venous systems showed no remarkable changes. The spinal cord was externally unremarkable. The ventricle were dilated. The cerebral cortex, white matter and thalamus revealed a mild atrophy. The basal ganglia were almost normal. The cerebellar hemispheres and vermis were diffusely soft and atrophic. But the dentate nuclei were well preserved. Histologically, there were severe status spongiosus, proliferation of astrocytes and loss of nerve cells in the cerebral cortex, thalamus and head of the caudate nuclei. The transverse fibers of the pons and the centripetal fibers of the cerebellar white matter were degenerated. In the cerebellum, there was a mild to moderate decrease in number and degeneration of Purkinje cells and granule cells and gliosis. There were numerous amyloid plaques which showed various morphological forms in the cerebellar cortex, cerebral cortex, thalamus and basal ganglia. The histological findings, including amyloid plaques and status spongiosus with softening foci in the white matter of his daughter's brain, were very similar to this patient. Transmission was succeeded by inoculating the daughter's brain tissue into a monkey. Judging from the familial occurrence, cerebellar ataxia, long clinical course and extensive amyloid plaque deposition throughout the central nervous system, both patients were diagnosed as having Gerstmann-Straussler syndrome. Some patients with GSS can be regarded as having a transmissible encephalopathy.",aged;amyloidosis;ataxia;autopsy;brain atrophy;brain spongiosis;case report;central nervous system;diagnosis;fatality;heredity;histology;human;human cell;preliminary communication,"Yoshimura, T.;Tateishi, J.;Tsujihata, M.",1984,,,0,
150,Structure-Activity Relationships and in Vivo Evaluation of Quinoxaline Derivatives for PET Imaging of beta-Amyloid Plaques,"This letter describes the synthesis, structure-activity relationships, and in vivo evaluation of a new series of 2-phenylquinoxaline (PQ) derivatives for imaging beta-amyloid (Abeta) plaques in Alzheimer's disease (AD). In experiments in vitro, the affinity of the derivatives for Abeta aggregates varied, with K i values of 0.895 to 1180 nM. In brain sections from AD patients, derivatives with a K i of less than 111 nM intensely labeled Abeta plaques, while those with values over 242 nM showed no marked labeling. In biodistribution experiments using normal mice, the derivatives showed good uptake into (4.69-7.59 %ID/g at 2 or 10 min postinjection) and subsequent washout from (1.48-3.08 %ID/g at 60 min postinjection) the brain. In addition, [(18)F]PQ-6 labeled Abeta plaques in vivo in APP transgenic mice, while it showed nonspecific binding in the white matter. Further structural optimization based on [(18)F]PQ-6 may lead to more useful PET probes for imaging Abeta plaques.",,"Yoshimura, M.;Ono, M.;Matsumura, K.;Watanabe, H.;Kimura, H.;Cui, M.;Nakamoto, Y.;Togashi, K.;Okamoto, Y.;Ihara, M.;Takahashi, R.;Saji, H.",2013,Jul 11,10.1021/ml4000707,0,
151,Statistical image analysis of cerebral blood flow in vascular dementia with small-vessel disease,"Small-vessel disease with dementia, which is the most frequent type of vascular dementia (VaD), often shows a cerebral blood flow (CBF) distribution with no obvious focal abnormalities and is therefore difficult to evaluate objectively. In this study, we combined CBF SPECT with 3-dimensional fractal analysis (3D-FA) to quantitatively assess the heterogeneity of CBF distribution and with 3-dimensional stereotactic surface projections (3D-SSP) to evaluate the distribution of CBF. We then evaluated the clinical validity of these techniques for the imaging diagnosis of VaD. Methods: The subjects consisted of 17 patients who were diagnosed as having VaD due to small-vessel disease (VaD group) on the basis of a full clinical examination, including history, neuropsychologic tests, neurologic examination, and neuroimaging methods, and 20 healthy volunteers (control group). CBF SPECT was performed with (99m)Tc-hexamethylpropyleneamine oxime, and the reconstructed images were subjected to image processing by 3D-FA and 3D-SSP. Based on the results, the fractal dimension (FD) was compared between the VaD and control groups, and the distribution pattern of CBF was examined in the VaD group. Results: The mean FD values in the VaD group and the control group were 1.093 ± 0.153 and 0.853 ± 0.062 (mean ± SD), respectively. The mean FD value in the VaD group was significantly higher than that in the control group (P < 0.0001). 3D-SSP analysis in the VaD group showed that there were 2 abnormal patterns: One was globally reduced blood flow in the whole cerebral cortex, and the other was a reduction mainly confined to the frontal region. Conclusion: CBF SPECT images showed higher mean FD values in the VaD group than in the control group, suggesting a difference in the heterogeneity of CBF. Image processing with 3D-SSP successfully revealed that reduced cortical blood flow could be divided into 2 patterns. Because image analysis techniques, such as 3D-FA and 3D-SSP, allowed the simple and objective evaluation of CBF in patients with VaD, these methods seem to be useful for detailed examination of the blood flow pattern detected by CBF SPECT in patients with VaD.",,"Yoshikawa, T.;Murase, K.;Oku, N.;Kitagawa, K.;Imaizumi, M.;Takasawa, M.;Nishikawa, T.;Matsumoto, M.;Hatazawa, J.;Hori, M.",2003,April,,0,
152,Prevalence of Sjögren's syndrome with dementia in a memory clinic,"Introduction: Sjögren's syndrome (SS) is an autoimmune disorder involving the exocrine glands, which affects 1.9-3.0% of the elderly population. Approximately 20% of all patients with SS have CNS involvement, including dementia, as a result of angiitis. Aims: The aim of the study was to clarify the prevalence and impact of SS among patients in a memory clinic. Methods: This study prospectively recruited patients with cognitive dysfunction in a memory clinic from 2007 to 2010. In addition to the examinations for dementia, the patients' levels of anti-SSA and SSB antibodies were measured. Schirmer's test and/or a lip biopsy were added if required. SS was diagnosed based on the American European consensus criteria. Results: Out of 276 cases who completed the examinations, 265 (97/168 males/females, mean age: 77.9, median MMSE score: 23) did not demonstrated cognitive decline. Sixteen (6.3%) and seven (2.7%) patients were positive for anti-SS-A and SS-B antibodies, respectively. Twenty patients (7.5%) were diagnosed with primary SS (mean age: 77.2 years old, median MMSE: 21). Seven of these patients had previously been diagnosed with MCI (VCIND: 5, aMCI: 2), and 13 had been diagnosed with dementia. All had asymmetrical focal hypoperfusion on SPECT, and eighteen had subcortical lesions on MRI. Twelve were treated for dementia (median time: 2.1 years), and their MMSE significantly improved (median MMSE: 26, p = 0.0019), while the non-SS subjects' MMSE declined (n = 126, median: 22). Conclusion: The patients with SS accounted for 7.5% of those with a cognitive decline as determined at a memory clinic, and are characterized by subcortical white matter lesions and asymmetric hypoperfusion. © 2012 Elsevier B.V.",donepezil;La antibody;prednisolone;Ro antibody;adult;aged;article;clinical article;controlled study;dementia;female;human;male;mild cognitive impairment;Mini Mental State Examination;neuroimaging;perfusion;priority journal;prospective study;single photon emission computer tomography;Sjoegren syndrome,"Yoshikawa, K.;Hatate, J.;Toratani, N.;Sugiura, S.;Shimizu, Y.;Takahash, T.;Ito, T.;Fukunaga, R.",2012,,,0,
153,Prevalence of Sjogren's syndrome with dementia in a memory clinic,"INTRODUCTION: Sjogren's syndrome (SS) is an autoimmune disorder involving the exocrine glands, which affects 1.9-3.0% of the elderly population. Approximately 20% of all patients with SS have CNS involvement, including dementia, as a result of angiitis. AIMS: The aim of the study was to clarify the prevalence and impact of SS among patients in a memory clinic. METHODS: This study prospectively recruited patients with cognitive dysfunction in a memory clinic from 2007 to 2010. In addition to the examinations for dementia, the patients' levels of anti-SSA and SSB antibodies were measured. Schirmer's test and/or a lip biopsy were added if required. SS was diagnosed based on the American European consensus criteria. RESULTS: Out of 276 cases who completed the examinations, 265 (97/168 males/females, mean age: 77.9, median MMSE score: 23) did not demonstrated cognitive decline. Sixteen (6.3%) and seven (2.7%) patients were positive for anti-SS-A and SS-B antibodies, respectively. Twenty patients (7.5%) were diagnosed with primary SS (mean age: 77.2 years old, median MMSE: 21). Seven of these patients had previously been diagnosed with MCI (VCIND: 5, aMCI: 2), and 13 had been diagnosed with dementia. All had asymmetrical focal hypoperfusion on SPECT, and eighteen had subcortical lesions on MRI. Twelve were treated for dementia (median time: 2.1 years), and their MMSE significantly improved (median MMSE: 26, p=0.0019), while the non-SS subjects' MMSE declined (n=126, median: 22). CONCLUSION: The patients with SS accounted for 7.5% of those with a cognitive decline as determined at a memory clinic, and are characterized by subcortical white matter lesions and asymmetric hypoperfusion.","Aged;Aged, 80 and over;Chi-Square Distribution;Dementia/blood/*complications/*epidemiology/radionuclide imaging;Female;Humans;Inosine Monophosphate;Iodine Isotopes;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory Disorders/*epidemiology/etiology;Mental Status Schedule;Middle Aged;Prevalence;Retrospective Studies;Sjogren's Syndrome/blood/*complications/*epidemiology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon","Yoshikawa, K.;Hatate, J.;Toratani, N.;Sugiura, S.;Shimizu, Y.;Takahash, T.;Ito, T.;Fukunaga, R.",2012,Nov 15,10.1016/j.jns.2012.07.060,0,
154,Fluid attenuation inversion recovery (FLAIR) images of dentatorubropallidoluysian atrophy: Case report,"The white matter lesions in a patient with late adult onset dentatorubropallidoluysian atrophy (DRPLA) were studied in detail by MRI using the fluid attenuation inversion recovery (FLAIR) technique. The patient was a 60 year old woman with a family history of DRPLA, in whom the number of CAG repeats in the DRPLA gene on chromosome 12 was expanded to 59 (normal allele 10). In addition to atrophy of the cerebral cortex, cerebellum, and pontomesencephalic tegmentum, the cerebral white matter and a part of the white matter tracts within the brainstem showed prominent high signal intensities on FLAIR images. These MR findings suggest that, in addition to the degeneration of the dentatorubral and pallidoluysian systems, the pathological process extends to the white matter in DRPLA. This could be important for differentiating DRPLA from other clinically similar diseases such as Machado-Joseph disease or Huntington's disease.",,"Yoshii, F.;Tomiyasu, H.;Shinohara, Y.",1998,September,,0,
155,Cerebral white matter bundle alterations in patients with dementia of Alzheimer type and patients with multi-infarct dementia--magnetic resonance imaging study,"The widths of the anterior white matter bundle (AWM) and the interhemispheric (AWM-TER) and intrahemispheric (AWM-TRA) bundles at the level of the foramen of Monro on horizontal inversion recovery MRI scans were measured in 17 patients with dementia of Alzheimer type (DAT), 16 patients with multi-infarct dementia (MID) and 47 age-matched normal subjects (NOR). The area of the corpus callosum (CC) on midsagittal spin-echo MRI scans was also measured in 12 DAT, 11 MID and 36 NOR. The Mini-mental score in patients with DAT was 20.8 +/- 5.9, which was not significantly different from that of 22.9 +/- 5.4 in patients with MID. The width of AWM was not significantly decreased in either DAT or MID compared with NOR. However, the width of AWM-TER in DAT and MID showed a significant decrease from that in NOR. The width of AWM-TRA was decreased significantly only in DAT. Compared with NOR, the area of the CC in DAT and MID was decreased by 7.0% (p less than 0.05) and 6.5%, respectively. The white matter bundle has an important role in the connectivity of the brain. Although loss of white matter occurs in both DAT and MID, the change appears more diffuse in DAT than MID.","Aged;Alzheimer Disease/ diagnosis;Brain/ pathology;Dementia, Multi-Infarct/ diagnosis;Humans;Magnetic Resonance Imaging;Middle Aged;Nerve Fibers/pathology;Nerve Tissue/ pathology","Yoshii, F.;Shinohara, Y.;Duara, R.",1990,Jan,,0,
156,Benign hereditary chorea 2: Pathological findings in an autopsy case,"Two Japanese families with benign hereditary chorea (BHC) 2 have recently been reported. BHC 2 is characterized by adult-onset non-progressive chorea, and by genetic abnormality in the locus of chromosome 8q21.3-q23.3. This differs from the genetic abnormality previously reported in BHC. Here we report the first autopsied case of a member of one of two known families with BHC 2. A normally developed woman recognized choreiform movements of her bilateral upper extremities beginning approximately at age 40. The movements had slowly spread to her trunk and lower extremities by approximately age 60. Generalized muscular hypotonia was also observed. The symptoms persisted until her death at the age 83, but had not worsened. Neuropathological examination revealed mild to moderate neuronal loss and astrocytosis in the striatum and decreased volume of cerebral white matter with astrocytosis bilaterally. Additionally, sparse but widely distributed neurofibrillary tangles and argyrophilic threads as well as scattered tufted astrocytes immunoreactive for 4-repeat isoform of tau were observed in the cerebrum, brainstem and cerebellum, showing 4-repeat tauopathy similar to that of progressive supranuclear palsy (PSP). Unique neuronal cytoplasmic inclusions were observed in the oculomotor nuclei; however, any specific immunoreactivities (e.g. ubiquitin and p62) were not detected, suggesting the presence of previously undescribed protein intracellular inclusions. Clinicopathologically, chorea accompanied with generalized muscular hypotonia seemed to be associated with mild degeneration of the striatum and cerebral white matter. The significance of PSP-like changes in the pathogenesis of BHC 2 remains to be elucidated. © 2012 Japanese Society of Neuropathology.",polyglutamine;protein p62;ubiquitin;adult;anemia;article;astrocytosis;autopsy;autosomal dominant disorder;benign hereditary chorea 2;brain degeneration;brain size;case report;chorea;depression;electron microscope;female;gait disorder;gliosis;human;immunoreactivity;laboratory test;muscle hypotonia;neuropathology;nuclear magnetic resonance imaging;oculomotor nucleus;pathology;priority journal;progressive supranuclear palsy;tauopathy;white matter;JEM 1400,"Yoshida, Y.;Nunomura, J.;Shimohata, T.;Nanjo, H.;Miyata, H.",2012,,,0,
157,White matter loss in the splenium of the corpus callosum in a case of posterior cortical atrophy: A diffusion tensor imaging study,"There have been several functional imaging studies using PET and SPECT to investigate posterior cortical atrophy (PCA). These studies have suggested dysfunction of corticocortical connections which is consistent with the occipitoparietal stream. However, there are no reports suggesting disturbance of the white matter that interconnects the temporal, parietal and occipital cortices. We measured fractional anisotropy (FA) in the genu and splenium of the corpus callosum and created color maps using diffusion tensor imaging (DTI), which is a relatively new MRI technique that allows visualization of the directionality of water diffusion, in a patient with PCA and compared these findings with those in 5 typical Alzheimer disease (AD) patients. The PCA patient was a 75-year-old man presenting with progressive complex visual disorder who satisfied the clinical diagnostic criteria for PCA. In 5 typical AD patients, the FA index in the splenium was higher than that in the genu; however, in the PCA patient, the FA index in the splenium was significantly lower than that in the genu. A DTI-based color map of the PCA patient showed reduction of anisotropy and fiber volume in the splenium. These findings suggest that the splenium of the corpus callosum secondarily degenerated due to neuronal degeneration of the temporal, parietal and occipital cortices and suggest that reduction of the",,"Yoshida, T.;Shiga, K.;Yoshikawa, K.;Yamada, K.;Nakagawa, M.",2004,2004,,0,
158,Memory impairment due to circumscribed infarct at the left dorsolateral prefrontal lobe,"A 65-year-old man experienced an embolism at the left dorsolateral prefrontal region of the brain (the inferior frontal gyrus and a part of the middle frontal gyrus). He was a known case of diabetes mellitus and atrial fibrillation. On evaluation his Mini-Mental State Examination (MMSE) score was 26, indicating the absence of dementia. His chief complaint was episodic memory impairment. On the Wechsler Memory Scale-Revised (WMS-R), he had lower scores for general memory, visual memory and verbal memory. In particular, his verbal memory was markedly impaired compared to visual memory. Tests performed to assess working memory, such as evaluation on the WMS-R for attention/ concentration in WMS-R and both parts A and B of the trail making test, revealed normal findings; this indicated that the patient had normal working memory. However, he complained of forgettingess of either phone numbers or routes, and this suggested the impairment of working memory in his daily life. In summary, he suffered from either episodic verbal memory or working memory impairment. His executive function test revealed a slight disturbance of set-exchange on the Wisconsin Card Sorting Test-Keio version. Such a case of memory impairment caused by a lesion in the left dorsolateral prefrontal lobe has rarely been reported.",aged;analytic method;article;attention;brain embolism;brain function;brain infarction;case report;comparative study;dementia;diabetes mellitus;episodic memory;frontal lobe;atrial fibrillation;human;male;memory;memory disorder;mental concentration;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;prefrontal cortex;rating scale;scoring system;single photon emission computer tomography;verbal memory;visual memory;working memory,"Yoshida, M.;Kuroda, H.",2008,,,0,
159,A 85 year old woman with the onset of progressive gait disturbance at 80 years of the age,"We report a 85 year old woman who had an onset of gait disturbance at 80 years of the age. She had a dizzy spell when she was 80 year old. She was evaluated at another hospital where paroxysmal tachycardia and sinus arrest lasting as long as 5.8 seconds were found. She was diagnosed as having sick sinus syndrome and a pace maker was inserted. She had a gradual onset of disturbance of gait shortly after the above dizzy spell. She became unable to walk fast and her steps became small. Neurologic examination at age 83 revealed small step gait with freezing episodes. Retropulsion was present. No motor weakness or origidity was noted. She had no tremor. Mentally she was alert and sound. Cranial nerves were essentially normal. Cranial CT scan revealed slight diffuse low density change in the bilateral cerebral white matter. She was treated with amantadine HCI and levodopa with carbidopa. Her gait and balance showed some improvement. She developed pneumonia and worsening of her gait when she was 85 years of the age, and she was admitted again to our hospital. She was mentally alert and sound but she showed marked freezing of gait with loss of postural reflex; she would have fallen down unless supported upon standing. Cranial nerves were again essentially normal. Her hospital course was complicated by pneumonia, DIC, and renal failure. She expired suddenly on the 10th day of her last admission. She was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had vascular parkinsonism due to lacunar state. However, paucity of vascular changes in her CT scan remained as a question. Other participants thought that she had nigral cell loss secondary to her aging and circulatory disturbance which would have been caused by her sick sinus syndrome. Post mortem examination revealed marked loss of nigral pigmented cells; the cell loss was diffusely seen in the substantia nigra. Neurofibrillary tangles were seen in the remaining neurons. In addition, gliosis was noted in the globus pallidus and the subthalamic nucleus, however, neuronal loss was very mild in those nuclei. In the superior colliculus, neuronal loss was mild, however, gliosis was seen. No clear neuronal loss was observed in the locus coeruleus, however, Lewy bodies were seen in the remaining neurons. Furthermore, Lewy bodies were also found in the substantia sigra. It was thought that she had progressive supranuclear play (PSP). Question was whether or not she was complicated by Parkinson's disease. Clinically, she had no rigidity or tremor. Pathologically, locus coeruleus did not show neuronal loss. Therefore, incidental Lewy body disease was raised as a possibility. Finally, it should be pointed out that she had no oculomotor disturbance or dementia, yet she had PSP. Her clinical features were those of pure akinesia. Pathologic changes were also relatively mild except for those in the substantia nigra. Possibility of post encephalitic parkinsonism without encephalitis was also discussed, however, over all distribution of her pathologic changes was more consistent with PSP.",amantadine;levodopa;aged;article;case report;computer assisted tomography;female;gait disorder;histopathology;human;human tissue;parkinsonism;progressive supranuclear palsy,"Yoritaka, A.;Hatttori, T.;Hattori, Y.;Mori, H.;Matsuoka, S.;Shirai, T.;Kondo, T.;Mizuno, Y.",1997,,,0,
160,Neuroanatomical Correlates of Hypophonia in Subcortical Vascular Cognitive Impairment,"BACKGROUND/AIMS: Early detection and intervention may alter the disease course of subcortical vascular cognitive impairment (SVCI). Patients with SVCI have white matter ischemia that disrupts connections between the cortex and subcortical gray matter and therefore manifest various symptoms such as motor disturbances and behavioral/cognitive dysfunction. Reduced vocal loudness, or hypophonia, is one of the common motor symptoms of SVCI, but few studies have systematically investigated it in this patient population. The main purpose of this investigation was to identify neural pathways underlying hypophonia in patients with SVCI. METHODS: Eighty-eight patients with SVCI and 21 normal controls performed phonation tasks. Diffusion tensor imaging data from 73 patients were utilized to measure white matter changes associated with hypophonia. RESULTS: Correlational analyses between white matter fractional anisotropy values and the decibel level of the ""sustained phonation"" task identified the left midbrain cerebral peduncle (corticobulbar tract), external capsule, corona radiata/internal capsule, and bilateral frontal white matter as possible neural correlates for hypophonia. CONCLUSION: Our results support the notion that hypophonia in SVCI patients might be caused by the impairment of the pyramidal and extrapyramidal systems. This study provides a unique contribution towards understanding the neuropathology of hypophonic features in this population.",Dementia;Hypophonia;Phonation;Stroke;Subcortical;Vascular,"Yoon, J. H.;Ahn, Y.;Kim, S. H.;Chin, J.;Park, S.;Na, D. L.",2017,,,0,
161,NOTCH3 variants in patients with subcortical vascular cognitive impairment: a comparison with typical CADASIL patients,"Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a common form of hereditary subcortical vascular cognitive impairment (SVCI), there is little data on the frequency of NOTCH3 variants in SVCI patients. We prospectively screened for NOTCH3 variants in consecutive SVCI patients who underwent brain magnetic resonance imaging and amyloid positron emission tomography as well as sequence analysis for mutational hotspots in the NOTCH3 gene. Among 117 patients with SVCI, 16 patients had either known mutations or variants of unknown significance in the NOTCH3 gene. There were no differences in clinical and neuroimaging features between SVCI patients with and without NOTCH3 variants, only except for a higher number of deep microbleeds in SVCI patients with NOTCH3 variants. Our findings suggest that there is a phenotypic entity of NOTCH3 variant that is similar to that of sporadic SVCI but not of typical CADASIL. Notably, 2 SVCI patients with NOTCH3 mutations showed significant amyloid burden, which challenges the prevailing concept that CADASIL represents the genetic model of pure small vessel disease.","Aged;Amyloidogenic Proteins/metabolism;Brain/metabolism/pathology;CADASIL/ genetics;Dementia, Vascular/ genetics/metabolism/pathology;Female;Genetic Association Studies;Genetic Variation/ genetics;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Models, Genetic;Mutation;Neuroimaging;Positron-Emission Tomography;Prospective Studies;Receptors, Notch/ genetics","Yoon, C. W.;Kim, Y. E.;Seo, S. W.;Ki, C. S.;Choi, S. H.;Kim, J. W.;Na, D. L.",2015,Aug,10.1016/j.neurobiolaging.2015.04.009,0,
162,Comparison of diffusion tensor imaging and voxel-based morphometry to detect white matter damage in Alzheimer's disease,"Regional atrophy of gray matter (GM) in Alzheimer's disease (AD) is well known; however, the relationship between macroscopic and microscopic changes of cerebral white matter (WM) is uncertain. The aim of this study was to investigate the pattern of GM, WM atrophy, and microscopic WM changes in the same individuals with AD. All subjects (10AD and 15 healthy controls [HC]) underwent a MRI scanning at 1.5 T, including a 3-dimensional volumetric scan and diffusion tensor imaging (DTI). We performed statistical parametric mapping (SPM) with DTI to evaluate the patterns of the microscopic WM changes, as well as voxel-based morphometry (VBM) for GM and WM volume changes between patients with AD and HC. GM atrophy was detected, mainly in posterior regions, and WM atrophy was similarly distributed, but less involved on VBM analysis. Unlike WM atrophy on VBM analysis, microscopic WM changes were shown in the medial frontal, orbitofrontal, splenium of the corpus callosum, and cingulum on DTI analysis with SPM. We demonstrated that the pattern of macroscopic WM atrophy was similar to GM atrophy, while microscopic WM changes had a different pattern and distribution. Our findings suggest that WM atrophy may preferentially reflect the secondary changes of GM atrophy, while microscopic WM changes start earlier in frontal areas before GM and WM atrophy can be detected macroscopically.","Aged;Alzheimer Disease/ pathology/psychology;Atrophy;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests","Yoon, B.;Shim, Y. S.;Hong, Y. J.;Koo, B. B.;Kim, Y. D.;Lee, K. O.;Yang, D. W.",2011,Mar 15,10.1016/j.jns.2010.11.012,0,
163,Interaction of white matter hyperintensities (WMHs) and apolipoprotein E (APOE) genotypes on cognition in patients with amnestic mild cognitive impairment (aMCI),"The clinical implications of WMHs in aMCI are inconclusive. Moreover, clinical interactions between APOE genotypes and WMHs remain unclear. This study was conducted to investigate the relationship between WMHs and cognitive functions and how this relationship interacted with APOE genotype in people with aMCI. This study included a total of 1472 patients with aMCI from the Clinical Research Center for Dementia of South Korea (CREDOS) and divided them into 3 groups according to the severity of WMHs as assessed by visual ratings of brain magnetic resonance images. The associations of WMHs with the various cognitive domains and with APOE epsilon 4 (varepsilon4) status were evaluated. After multivariable adjustments, the severity of WMHs was independently associated with semantic/phonemic verbal fluency and Stroop test-color reading, while APOE varepsilon4 status was associated with verbal and visual memory-immediate, delayed recall, and recognition. Moreover, there were interaction between WMHs and APOE varepsilon4 status in semantic verbal fluency (animal, P=0.033; supermarket, P=0.047)/Stroop test-color reading (P=0.024). WMHs independently deleteriously affected frontal executive functions in aMCI patients, regardless of APOE varepsilon4 presence. Furthermore, APOE varepsilon4 possession caused a rapid decline in frontal executive functions with the increase in the WMHs severity (vs. absence), suggesting that WMHs and APOE varepsilon4 genotypes synergistically contribute to frontal executive dysfunctions in aMCI.",Aged;Apolipoproteins E/ genetics;Brain/ pathology;Cognition;Executive Function;Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/blood/genetics/pathology;Mild Cognitive Impairment/blood/ genetics/pathology;Neuroimaging;Neuropsychological Tests;Severity of Illness Index;Stroop Test,"Yoon, B.;Shim, Y. S.;Cheong, H. K.;Kim, Y. D.;Lee, K. O.;Hong, Y. J.;Oh, Y. S.;Na, H. R.;Kim, B. C.;Choi, S. H.;Yang, D. W.",2013,Nov-Dec,10.1016/j.archger.2013.04.008,0,
164,Efficacy of cilostazol augmentation treatment in Alzheimer's disease with white matter lesion by FDG PET,"Objective: Cilostazol is a common phosphodiesterase 3 inhibitor which is recently being studied as a possible medication for Alzheimer's disease patients. This study aims to measure the AD modifying efficacy of cilostazol using FDG PET. Method: In order to test the efficacy of cilostazol, we conducted 24-week, randomized, double-blind, placebo-controlled, parallel-group study FDG PET in AD patients with white matter lesion. 36 participants (18 in the cilostazol group and 18 in the placebo group) completed this study throughout two times of FDG PET imaging and three times of clinical neuropsychological tests. Results: There were no decreases of glucose uptake observed in the cilostazol group; however, there were significant metabolic decreases at the both parietal and frontal lobes in the placebo group that are observed by paired T-tests. When we compared differences of the change from preto post-medicated conditions, the glucose uptake of the left inferior frontal gyrus was significantly improved in the cilostazol group (p < 0.005). There were no differences in the MMSE, ADAScog, ADCS-ADL, and the CDR sum changes from baseline between two groups. Conclusion: According to our FDG PET results, cilostazol appears to delay cerebral metabolic decrease in AD patients while placebo group shows hypometabolism inmany regions. Among those, left inferior frontal gyrus is more prominently affected in cilostazol treated patients. However, effects on clinical functions need to be tested in further studies with the larger sample size.",white matter lesion;Alzheimer disease;human;patient;inferior frontal gyrus;glucose transport;imaging;sample size;neuropsychological test;Student t test;drug therapy;frontal lobe;Mini Mental State Examination;cilostazol;placebo;phosphodiesterase III inhibitor,"Yoo, H. B.;Choi, J. S.;Yoon, E. J.;Lee, H. Y.;Kim, Y. K.;Lee, H.;Lee, J. Y.",2013,,10.1017/s1041610213002147,0,
165,Brain perfusion SPECT with (99m)Tc-bicisate: Comparison with PET measurement and linearization based on permeability-surface area product model,"To characterize a recently introduced cerebral perfusion tracer, (99m)Tc- bicisate, single photon emission computed tomography (SPECT) images of (99m)Tc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the (15)O steady-state method in 10 cases of cerebrovascular disease and dementia. (99m)Tc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which (99m)Tc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of (99m)Tc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in (99m)Tc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.",,"Yonekura, Y.;Tsuchida, T.;Sadato, N.;Nishizawa, S.;Iwasaki, Y.;Mukai, T.;Konishi, J.;Shibasaki, H.",1994,1994,,0,
166,"Imaging discrepancies between magnetic resonance imaging and brain perfusion single-photon emission computed tomography in the diagnosis of Alzheimer's disease, and verification with amyloid positron emission tomography","BACKGROUND: In the diagnosis of Alzheimer's disease (AD), discrepancies are often observed between magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) findings. MRI, brain perfusion SPECT, and amyloid positron emission tomography (PET) findings were compared in patients with mild cognitive impairment or early AD to clarify the discrepancies between imaging modalities. METHODS: Several imaging markers were investigated, including the cortical average standardized uptake value ratio on amyloid PET, the Z-score of a voxel-based specific regional analysis system for AD on MRI, periventricular hyperintensity grade, deep white matter hyperintense signal grade, number of microbleeds, and three indicators of the easy Z-score imaging system for a specific SPECT volume-of-interest analysis. Based on the results of the regional analysis and the three indicators, we classified patients into four groups and then compared the results of amyloid PET, periventricular hyperintensity grade, deep white matter hyperintense signal grade, and the numbers of microbleeds among the groups. RESULTS: The amyloid deposition was the highest in the group that presented typical AD findings on both the regional analysis and the three indicators. The two groups that showed an imaging discrepancy between the regional analysis and the three indicators demonstrated intermediate amyloid deposition findings compared with the typical and atypical groups. The patients who showed hippocampal atrophy on the regional analysis and atypical AD findings using the three indicators were approximately 60% amyloid-negative. The mean periventricular hyperintensity grade was highest in the typical group. CONCLUSIONS: Patients showing discrepancies between MRI and SPECT demonstrated intermediate amyloid deposition findings compared with patients who showed typical or atypical findings. Strong white matter signal abnormalities on MRI in patients who presented typical AD findings provided further evidence for the involvement of vascular factors in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/radionuclide imaging;Ambulatory Care Facilities;Amyloid/ metabolism;Brain/blood supply/radionuclide imaging;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/ diagnosis;Neuroimaging;Regional Blood Flow;Thiazoles;Tomography, Emission-Computed, Single-Photon/ methods","Yokoyama, S.;Kajiya, Y.;Yoshinaga, T.;Tani, A.;Hirano, H.",2014,Jun,10.1111/psyg.12047,0,
167,Pathological background of subcortical hyperintensities on diffusion-weighted images in a case of neuronal intranuclear inclusion disease,"Aims: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with eosinophilic intranuclear inclusion bodies. The variable symptoms of NIID increase the difficulty in an antemortem diagnosis. NIID shows leukoencephalopathy on brain magnetic resonance imaging MRI, but the significance of the radiological findings have not been clarified. Methods: We examined an autopsied case of NIID with subcortical linear hyperintensities on diffusion weighted imaging (DWI) and leukoencephalopathy on fluid attenuation inversion recovery (FLAIR) imaging. Semiquantitative analysis was performed by merging coronal sections of DWI and identical hematoxylineosin (H & E) stained brain specimens. The severity of spongiotic changes, the common pathological findings of NIID, were quantified and compared with MRI lesions classified by DWI signals. Results: The white matter showed diffuse myelin pallor, and multiple focal spongiotic changes were present in the subcortical white matter proximal to the Ufibers. Spongiotic changes were restricted in the lesions with subcortical linear DWI high signals. Conclusion: Subcortical DWI high signals in NIID strongly correlate with pathological spongiotic changes of NIID. Subcortical spongiotic changes may be a characteristic finding of NIID.",hematoxylin;myelin;aged;article;brain cortex;case report;degenerative disease;diffusion weighted imaging;female;histopathology;human;human tissue;image analysis;leukoencephalopathy;neuronal intranuclear inclusion disease;priority journal;white matter,"Yokoi, S.;Yasui, K.;Hasegawa, Y.;Niwa, K.;Noguchi, Y.;Tsuzuki, T.;Mimuro, M.;Sone, J.;Watanabe, H.;Katsuno, M.;Yoshida, M.;Sobue, G.",2016,,10.5414/np300961,0,
168,Comparison of the Alzheimer's Disease Assessment Scale Cognitive Subscale and the Vascular Dementia Assessment Scale in differentiating elderly individuals with different degrees of white matter changes. The LADIS Study,"BACKGROUND/AIMS: The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) is a widely used rating instrument. The Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog) includes additional tests reflecting mental speed and executive functions. The objective of this study was to compare the results of the two scales among subjects with various degrees of white matter hyperintensities (WMHs). METHODS: In the multicentre, multinational Leukoaraiosis and Disability in the Elderly (LADIS) study, 616 non-disabled subjects between the ages of 65 and 84 were examined using MRI, the ADAS-cog and VADAS-cog. The WMH rating from the MRI divided the patients into groups of mild (n = 280), moderate (n = 187) and severe (n = 149) degrees of change. RESULTS: Covariance analysis controlling for the effect of age and education revealed that the ADAS-cog differentiated only the mild and severe WMH groups, while the differences between all three groups were highly significant with the VADAS-cog. CONCLUSIONS: The VADAS-cog significantly differentiated between all the white matter groups. In comparison, the ADAS-cog differentiated only severe changes. Accordingly, the VADAS-cog may be a more sensitive endpoint in studies of patients with white matter load and vascular burden of the brain.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/psychology;Brain/*pathology;Dementia, Vascular/*diagnosis/psychology;Disability Evaluation;Female;Follow-Up Studies;Humans;Leukoaraiosis/*diagnosis/psychology;*Magnetic Resonance Imaging;Male;Mental Recall/physiology;Neuropsychological Tests/*statistics & numerical data;Problem Solving/physiology;Prospective Studies;Psychometrics/statistics & numerical data;Reaction Time/physiology;Reproducibility of Results;Retention (Psychology)/physiology;Statistics as Topic;Verbal Learning/physiology","Ylikoski, R.;Jokinen, H.;Andersen, P.;Salonen, O.;Madureira, S.;Ferro, J.;Barkhof, F.;van der Flier, W.;Schmidt, R.;Fazekas, F.;Scheltens, P.;Waldemar, G.;Salvadori, E.;Pantoni, L.;Inzitari, D.;Erkinjuntti, T.",2007,,10.1159/000103865,0,
169,"Cognitive variations among vascular dementia subtypes caused by small-, large-, or mixed-vessel disease","INTRODUCTION: Vascular dementia (VaD) is a heterogeneous disease that can vary in clinical presentation and cognitive profile. The cognitive profiles of different VaD subtypes depend on the anatomical distribution of the vascular insults that have been documented. MATERIAL AND METHODS: We reviewed demographic, cognitive, and imaging data in 402 patients who were clinically diagnosed with VaD between January 2002 and June 2012 at the First Affiliated Hospital of Gan Nan Medical College in Ganzhou, China. RESULTS: Based on magnetic resonance imaging (MRI) results, patients were classified as having large- (24.1%), small- (70.4%), or mixed-vessel VaD (5.5%). Hypertension was the most prevalent risk factor (81%), followed by smoking (37%), hyperlipidemia (35%), and diabetes (27%). Hyperlipidemia, cardiac risk factors (history of cardiovascular disease, heart valve disorder) and carotid stenosis were more frequent in patients with large-vessel disease compared to those with small-vessel or mixed-vessel disease (p < 0.001). A median of 4 (maximum 11) cognitive domains were impaired in each VaD patient. After memory dysfunction, executive defects were the most prevalent (68.9%), and neurobehavioral dysfunction was the most rare (13.2%). Patients with small-vessel VaD showed more executive dysfunction than patients with large-vessel and mixed-vessel VaD (p < 0.05), whereas patients with large-vessel VaD had a higher prevalence of visuospatial or language dysfunction (p < 0.05). CONCLUSIONS: The results indicate that specific subtypes and underlying vascular mechanisms will help predict clinical courses and produce more focused treatment and prevention of VaD.",cognition;domain;vascular dementia,"Ying, H.;Jianping, C.;Jianqing, Y.;Shanquan, Z.",2016,Aug 1,10.5114/aoms.2016.60962,0,
170,Inverse relationship between apolipoprotein A-I and cerebral white matter lesions: a cross-sectional study in middle-aged and elderly subjects,"BACKGROUND: Apolipoprotein A-I (apoA-I), the major protein for high density lipoprotein, is essential for reverse cholesterol transport. Decreased serum levels of apoA-I have been reported to correlate with subcortical infarction and dementia, both of which are highly related to white matter lesions (WMLs). However, the association between apoA-I and WMLs has never been investigated. In this study, we sought to investigate the association between apoA-I and the presence of WMLs in middle-aged and elderly subjects. METHODS: Consecutive patients aged 50 years and older of our department were prospectively enrolled in this study (n = 1282, 606 men and 676 women, 65.9 +/- 9.4 years). All participants underwent MRI scans to assess the presence and severity of WMLs. Multivariate logistic regression analyses were performed to examine the association of apoA-I with WMLs. RESULTS: Patients with WMLs were older and showed significantly higher proportion of male sex, hypertension, diabetes mellitus, previous stroke, and coronary heart disease whereas levels of total cholesterol, high density lipoprotein cholesterol, and apoA-I were lower. After adjustment for potential confounders, the lowest apoA-I quartile was independently associated with an increased risk of WMLs (odds ratio: 1.87, 95% confidence interval: 1.29-2.72). In sex-specific analyses, this relationship was observed only in women. CONCLUSIONS: Our findings demonstrated that apoA-I was inversely associated with the presence of WMLs in middle-aged and elderly subjects. This results suggest that therapies which increase apoA-I concentration may be beneficial to reduce the risk of WMLs, dementia and stroke.",Aged;Apolipoprotein A-I/*metabolism;Cross-Sectional Studies;Female;Humans;Leukoaraiosis/*epidemiology/*metabolism;Magnetic Resonance Imaging;Male;Middle Aged;Risk,"Yin, Z. G.;Li, L.;Cui, M.;Zhou, S. M.;Yu, M. M.;Zhou, H. D.",2014,,10.1371/journal.pone.0097113,0,
171,Report of two Chinese families and a review of Mainland Chinese CADASIL patients,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease caused by a mutation of the NOTCH3 gene. The clinical information of two CADASIL families was studied and mutation analysis of the NOTCH3 gene was performed by DNA direct sequencing. Published studies of Mainland Chinese CADASIL patients were reviewed and reanalyzed. The patients in the two families showed migraine with aura, stroke and cognitive decline. Cranial MRI revealed subcortical white matter infarcts and leukoencephalopathy. Two previously reported mutations of the NOTCH3 gene, c.397C > T and c.268C > T, were identified and cosegregated with the disease. The main clinical features, cranial MRI and pathological changes in Mainland Chinese CADASIL patients were similar to those in other regions. The frequency of migraine may be lower than that in Europe, but similar to that in Asia. Eight different NOTCH3 gene mutations were reported among Mainland Chinese CADASIL patients; of these, the c.322C > T mutation has not been reported in other regions. This study supports that the clinical features of Mainland Chinese CADASIL patients are similar to those seen in other regions and that exon 3 and exon 4 of the NOTCH3 gene are the mutation hotspots in Mainland Chinese CADASIL patients. © 2008 Elsevier B.V. All rights reserved.",Notch3 receptor;adult;article;brain cortex;brain infarction;CADASIL;Chinese;clinical article;cognitive defect;controlled study;exon;female;gene mutation;genetic analysis;genetic identification;genotype;geographic distribution;human;leukoencephalopathy;male;migraine;migraine with aura;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident;white matter,"Yin, X. z;Ding, M. p;Zhang, B. r;Liu, J. r;Zhang, L.;Wang, P. z;Zhou, F. y;Zhao, G. h",2009,,,0,
172,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Phenotypic and mutational spectrum in patients from mainland China,"AIMS: To analyze the NOTCH3 gene mutations in patients from mainland China clinically suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and evaluate large intracranial arteries in CADASIL patients. METHODS: We performed clinical, neuroimaging and NOTCH3 gene (exons 2-23) examinations in 47 subjects from 34 families. Large intracranial arteries were assessed using magnetic resonance angiography (MRA) in 19 cases with NOTCH3 gene variants. RESULTS: Screening of exons 3 and 4 identified six different known mutations in eight families and two novel mutations in two families. Further screening of the remaining exons identified p.R1175W, a variant of unknown significance. The incidence of NOTCH3 mutations was 29.4% (10/34). Five cases with NOTCH3 mutations showed intracranial atherosclerosis. One patient developed cerebral infarction due to left middle cerebral artery occlusion (M2 segment). CONCLUSIONS: The NOTCH3 mutation spectrum in our group was diverse and consistent with those in Caucasians but differed from those in Korea and Taiwan. The screening strategy used in Caucasian populations can be applied to mainland Chinese patients. Atherosclerosis of the large intracranial arteries involvement does not exclude CADASIL diagnosis.","Adult;Aged;Asian Continental Ancestry Group/genetics;CADASIL/*genetics;DNA Mutational Analysis;Female;Genetic Linkage;Humans;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/*genetics;Neurologic Examination;Pedigree;Receptors, Notch/*genetics;Retrospective Studies;Cadasil;NOTCH3 gene;mainland China;mutation","Yin, X.;Wu, D.;Wan, J.;Yan, S.;Lou, M.;Zhao, G.;Zhang, B.",2015,,10.3109/00207454.2014.951929,0,
173,Multimodal Voxel-Based Meta-Analysis of White Matter Abnormalities in Alzheimer's Disease,"An increasing number of MRI investigations suggest that patients with Alzheimer's disease (AD) show not only gray matter decreases but also white matter (WM) abnormalities, including WM volume (WMV) deficits and integrity disruption of WM pathways. In this study, we applied multimodal voxel-wise meta-analytical methods to study WMV and fractional anisotropy in AD. Fourteen studies including 723 participants (340 with AD and 383 controls) were involved. The meta-analysis was performed using effect size signed differential mapping. Significant WMV reductions were observed in bilateral inferior temporal gyrus, splenium of corpus callosum, right parahippocampal gyrus, and hippocampus. Decreased fractional anisotropy was identified mainly in left posterior limb of internal capsule, left anterior corona radiata, left thalamus, and left caudate nucleus. Significant decreases of both WMV and fractional anisotropy were found in left caudate nucleus, left superior corona radiata, and right inferior temporal gyrus. Most findings showed to be highly replicable in the jackknife sensitivity analyses. In conclusion, AD patients show widespread WM abnormalities mainly in bilateral structures related to advanced mental and nervous activities.",,"Yin, R. H.;Tan, L.;Liu, Y.;Wang, W. Y.;Wang, H. F.;Jiang, T.;Zhang, Y.;Gao, J.;Canu, E.;Migliaccio, R.;Filippi, M.;Gorno-Tempini, M. L.;Yu, J. T.",2015,,10.3233/jad-150139,0,
174,Brain imaging of mild cognitive impairment and Alzheimer's disease,"The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.",,"Yin, C.;Li, S.;Zhao, W.;Feng, J.",2013,Feb 15,10.3969/j.issn.1673-5374.2013.05.007,0,
175,Distribution of the corticobulbar tract in the internal capsule,"It is generally thought that the corticobulbar tract descends through the genu of the internal capsule (IC). There have been several reports that genu lesions cause bulbar symptoms such as facial palsies, dysarthria, and dysphagia. However, the precise location of the corticobulbar tract in the",,"Yim, S. H.;Kim, J. H.;Han, Z. A.;Jeon, S.;Cho, J. H.;Kim, G. S.;Choi, S. A.;Lee, J. H.",2013,15,,0,
176,Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: application to proton MR Spectroscopy (MRS) in HIV-related neurological injury,"We present the multi-dimensional Receiver Operating Characteristic (ROC) surface, a plot of the true classification rates of tests based on levels of biological markers, for multi-group discrimination, as an extension of the ROC curve, commonly used in two-group diagnostic testing. The volume under this surface (VUS) is a global accuracy measure of a test to classify subjects in multiple groups and useful to detect trends in marker measurements. We used three-dimensional ROC surfaces, and associated VUS, to discriminate between HIV-negative (NEG), HIV-positive neurologically asymptomatic (NAS) subjects and patients with AIDS demential complex (ADC), using brain metabolites measured by proton MRS. These were ratios of markers of inflammation, Choline (Cho) and myoinositol (MI), and brain injury, N-acetyl aspartate (NAA), divided by Creatine (Cr), measured in the basal ganglia and the frontal white matter. Statistically significant trends were observed in the three groups with respect to MI/Cr (VUS=0.43; 95% confidence interval (CI) 0.33-0.53), Cho/Cr (0.36; 0.27-0.45) in the basal ganglia and NAA/Cr in the frontal white matter (FWM) (0.29; 0.20-0.38), suggesting a continuum of injury during the neurologically asymptomatic stage of HIV infection, particularly with respect to brain inflammation. Adjusting for age increased the combined classification accuracy of age and NAA/Cr (p=0.053). Pairwise comparisons suggested that neuronal damage associated with NAA/Cr decreases was mainly observed in individuals with ADC, raising issues of synergism between HIV infection and age and possible acceleration of neurological deterioration in an aging HIV-positive population. The three-dimensional ROC surface and its associated VUS are useful for assessing marker accuracy, detecting data trends and offering insight in disease processes affecting multiple groups.","AIDS Dementia Complex/*diagnosis/metabolism/pathology;Adult;Aging/physiology;Algorithms;Aspartic Acid/analogs & derivatives/metabolism;Basal Ganglia/pathology;Brain/pathology;Brain Chemistry;Choline/metabolism;Creatinine/metabolism;Female;HIV Infections/pathology;Humans;Image Processing, Computer-Assisted/*statistics & numerical data;Inositol/metabolism;Magnetic Resonance Imaging/*statistics & numerical data;Male;Middle Aged;Predictive Value of Tests;ROC Curve","Yiannoutsos, C. T.;Nakas, C. T.;Navia, B. A.",2008,Mar 1,10.1016/j.neuroimage.2007.09.056,0,
177,Clinical analysis of 40 cases of neurosyphilis,"Objective: To study the clinical features of neurosyphilis. Methods: The clinical data of 40 patients with neurosyphilis were analyzed retrospectively. Results: The initial symptoms of 40 neurosyphilis patients included dementia (12 cases), ataxia (6 cases), absence of symptoms (4 cases), epilepsia (4 cases), insanity (3 cases), cranial nerve injury (2 cases), peripheral nerve injury (3 cases), intracranial hypertension (2 cases), acute cerebral infarction (2 cases), and myeloterosis (2 cases). Treponema pallidum hemagglutination assay (TPHA) test of both serum and CSF samples in the 40 patients were all positive. CT and/or MRI of cranium indicated normal (1 case), brain atrophy and hydrocephalus (13 cases), and plenty of abnormal signals in the brain (29 cases). Electrophysiology examination showed EEG medium to severe abnormal in 7 cases of epilepsy or insanity, and EMG abnormal in 2 cases of peripheral nerve injury. After large doses Penicillin treatment, 34 cases condition had significantly improved, 2 cases were ineffective. Conclusions: The clinical presentation of neurosyphilis is various and lack of specificity. Treatment with penicillin is worked. It is helpful to diagnose that the case history is combined with TPHA test of blood and CSF, electrophysiology and imaging examination.",penicillin derivative;assay;blood;brain;brain atrophy;brain infarction;cerebrospinal fluid;clinical feature;clinical study;cranial nerve injury;dementia;electroencephalogram;electromyogram;electrophysiology;epilepsy;examination;hemagglutination;human;hydrocephalus;imaging;intracranial hypertension;mental disease;neurosyphilis;nuclear magnetic resonance imaging;patient;peripheral nerve injury;serum;skull;Treponema pallidum;Treponema pallidum hemagglutination test,"Yi, F.;Xiao, B.;Li, G. L.",2010,,,0,178
178,Clinical analysis of 40 cases of neurosyphilis,"Objective: To study the clinical features of neurosyphilis. Methods: The clinical data of 40 patients with neurosyphilis were analyzed retrospectively. Results: The initial symptoms of 40 neurosyphilis patients included dementia (12 cases), ataxia (6 cases), absence of symptoms (4 cases), epilepsia (4 cases), insanity (3 cases), cranial nerve injury (2 cases), peripheral nerve injury (3 cases), intracranial hypertension (2 cases), acute cerebral infarction (2 cases), and myeloterosis (2 cases). Treponema pallidum hemagglutination assay (TPHA) test of both serum and CSF samples in the 40 patients were all positive. CT and/or MRI of cranium indicated normal (1 case), brain atrophy and hydrocephalus (13 cases), and plenty of abnormal signals in the brain (29 cases). Electrophysiology examination showed EEG medium to severe abnormal in 7 cases of epilepsy or insanity, and EMG abnormal in 2 cases of peripheral nerve injury. After large doses Penicillin treatment, 34 cases condition had significantly improved, 2 cases were ineffective. Conclusions: The clinical presentation of neurosyphilis is various and lack of specificity. Treatment with penicillin is worked. It is helpful to diagnose that the case history is combined with TPHA test of blood and CSF, electrophysiology and imaging examination.",,"Yi, F.;Xiao, B.;Li, G. L.",,2010,,0,
179,Multiple sclerosis: specificity of MR for diagnosis,"The specificity of magnetic resonance (MR) imaging in the diagnosis of multiple sclerosis (MS) has not been measured systematically. Conventional MR head images with sagittal localizer and axial multiple-echo sequences with long repetition times were obtained in 92 patients with clinically verified MS (Schumacher criteria), 100 healthy volunteers, 60 subjects with hypertension, and eight patients with dementia. Two readers, without the aid of any clinical or demographic information, classified each of the 260 studies as MS or not MS. The readers classified the studies again after being supplied with the subjects' ages and sex. True-negative and true-positive diagnoses of MS were tabulated. The specificity of the MR diagnosis of MS (true-negative results in proportion to all non-MS studies) was 95%-99% with all the control groups included. There is a small risk of misinterpreting incidental periventricular white matter foci as plaques of MS in MR studies.","Adult;Aged;Aged, 80 and over;Brain/pathology;False Positive Reactions;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multiple Sclerosis/ diagnosis;Sensitivity and Specificity","Yetkin, F. Z.;Haughton, V. M.;Papke, R. A.;Fischer, M. E.;Rao, S. M.",1991,Feb,10.1148/radiology.178.2.1987607,0,
180,High-signal foci on MR images of the brain: Observer variability in their quantification,"Foci of high signal in the cerebral white matter are common incidental findings on MR images of the brain of control subjects or patients with a variety of diseases. Although the number of foci has been reported to correlate with age and several risk factors, the degree of observer variability in quantifying foci has not been reported. We used kappa statistics to determine radiologists' agreement in counting high-signal- intensity foci on MR images obtained in healthy volunteers and in patients with hypertension. Before interpreting the images, one pair of radiologists studied 30 routine MR images and reached consensus on differentiating high- signal foci from other foci of high intensity caused by normal structures (e.g., deep gyri or Virchow-Robin spaces). These two observers then independently determined the number of foci in the study group. Using their own criteria, other radiologists independently counted the foci. Agreement between observers was determined with the kappa statistic. The results showed fair agreement between the radiologists who first reached a consensus in counting foci of hyperintensity and poor agreement between the other observers. We conclude that in order to compare the frequency of foci of hyperintensity in different groups of patients, observer variability must be controlled. Studies without proper control subjects may lead to incorrect conclusions regarding the correlation of focal hyperintensities and various risk factors.",,"Yetkin, F. Z.;Haughton, V. M.;Fischer, M. E.;Papke, R. A.;Daniels, D. L.;Mark, L. P.;Hendrix, L. E.;Asleson, R. J.;Johansen, J.",1992,1992,,0,
181,Improvement in Tc-99m HMPAO brain SPECT findings during donepezil therapy in a patient with pure akinesia,"A 58-year-old man presented with a history of disturbance in initiating gait. His history revealed meningoencephalitis five years prior to admission. Neurological examination included gait disturbance as difficulty in initiation and a hesitating speech with many freezing episodes and micrographia Magnetic resonance imaging (MRI) showed diffuse hyperintensity of frontal subcortical white matter on T2 weighted images. He was diagnosed with PA. L-Dopa up to the dosages of 1000 mg/ day and selegiline 10 mg/day were given. First brain SPECT using technetium-99m labeled D,L-hexamethylpropylene amine oxime (Tc-99m HMPAO) was performed when he was taking L-dopa and selegiline. In visual evaluation, hypoperfusion in bilateral frontoparietal cortex was seen (Fig. 2). Treatment with L-dopa and selegiline produced no benefit. Donepezil 10 mg/day was begun. This therapy regimen resulted in dramatic clinical improvement within several days that was confirmed by blinded raters who watched the patient's video recordings. During this response second brain perfusion SPECT study was repeated during donepezil therapy. Markedly increased perfusion in bilateral frontoparietal cortex was observed. This is the first case of PA to develop possibly after an episode of bacterial pneumococcal meningoencephalitis and who responded to donepezil as documented by changes in clinical findings and Tc-99m HMPAO brain SPECT studies.","Alexia, Pure/drug therapy/radionuclide imaging;Brain/ radionuclide imaging;Cholinesterase Inhibitors/administration & dosage;Dementia/drug therapy/radionuclide imaging;Gait Disorders, Neurologic/ drug therapy/ radionuclide imaging;Indans/ administration & dosage;Neurodegenerative Diseases/ drug therapy/ radionuclide imaging;Piperidines/ administration & dosage;Radiopharmaceuticals;Recovery of Function/drug effects;Syndrome;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/methods;Treatment Outcome","Yener, G. G.;Kaya, G. C.;Ozturk, V.;Akdal, G.",2005,Oct,,0,
182,Joint reconstruction of white-matter pathways from longitudinal diffusion MRI data with anatomical priors,"We consider the problem of reconstructing white-matter pathways in a longitudinal study, where diffusion-weighted and T1-weighted MR images have been acquired at multiple time points for the same subject. We propose a method for joint reconstruction of a subject's pathways at all time points given the subject's entire set of longitudinal data. We apply a method for unbiased within-subject registration to generate a within-subject template from the T1-weighted images of the subject at all time points. We follow a global probabilistic tractography approach, where the unknown pathway is represented in the space of this within-subject template and propagated to the native space of the diffusion-weighted images at all time points to compute its posterior probability given the images. This ensures spatial correspondence of the reconstructed pathway among time points, which in turn allows longitudinal changes in diffusion measures to be estimated consistently along the pathway. We evaluate the reliability of the proposed method on data from healthy controls scanned twice within a month, where no changes in white-matter microstructure are expected between scans. We evaluate the sensitivity of the method on data from Huntington's disease patients scanned repeatedly over the course of several months, where changes are expected between scans. We show that reconstructing white-matter pathways jointly using the data from all time points leads to improved reliability and sensitivity, when compared to reconstructing the pathways at each time point independently.","Adult;Algorithms;Brain/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Huntington Disease/pathology;Image Processing, Computer-Assisted/ methods;Longitudinal Studies;Male;Middle Aged;Neural Pathways/ pathology;Reproducibility of Results;White Matter/ pathology;Diffusion MRI;Longitudinal data analysis;Tractography","Yendiki, A.;Reuter, M.;Wilkens, P.;Rosas, H. D.;Fischl, B.",2016,Feb 15,,0,
183,Subtypes of mild cognitive impairment among the elderly with major depressive disorder in remission,"BACKGROUND: Cognitive impairment in remitted late-life depression varies and might be associated with greater risk of dementia in some individuals. This study aimed to classify the subtypes of mild cognitive impairment (MCI) in late-life major depressive disorder in remission and to examine their clinical correlates and structural magnetic resonance imaging (MRI) features. METHODS: Elderly patients with major depressive disorder in remission and elderly comparisons were examined by a comprehensive battery of cognitive tasks. Proposed diagnostic criteria were used for MCI classification, and the degree of brain atrophy and white matter hyperintensity on MRI were evaluated. RESULTS: We found information-processing speed and memory were independent cognitive domains associated with late-life remitted major depressive disorder. Of the study cohort, 52.3% met the definition of MCI, including 28.5% with amnestic MCI (aMCI) and 23.8% with nonamnestic MCI (naMCI). A clinical correlate of aMCI was the late-onset of disorder (OR = 4.76; 95% CI = 1.57, 14.40) and of naMCI was a higher score on the Framingham stroke risk scale (OR = 1.39; 95% CI = 1.12, 1.72). The odds ratio of highest quartile of ventricular atrophy for aMCI compared to the comparisons was 3.65 (95% CI = 1.22, 10.96). CONCLUSIONS: The central cognitive impairments among the elderly with major depressive disorder in remission were memory and information-processing speed, and over half of the subjects met the MCI diagnostic criteria. Different risk factors existed for the subtypes of aMCI and naMCI. Later-age onset of first episode and ventricular atrophy were associated with aMCI, whereas vascular risk factor were associated with naMCI. We suggest there were different pathogeneses between aMCI and naMCI in late-life major depressive disorder.","Aged;Atrophy/pathology;Brain/ pathology;Case-Control Studies;Depressive Disorder, Major/complications/ diagnosis/pathology;Female;Humans;Magnetic Resonance Imaging/methods/psychology;Male;Mental Processes;Mild Cognitive Impairment/complications/ diagnosis/pathology;Nerve Fibers, Myelinated/pathology;Neuroimaging/methods/psychology;Neuropsychological Tests/statistics & numerical data;Remission Induction;Risk Factors","Yeh, Y. C.;Tsang, H. Y.;Lin, P. Y.;Kuo, Y. T.;Yen, C. F.;Chen, C. C.;Liu, G. C.;Chen, C. S.",2011,Nov,10.1097/JGP.0b013e318202clc6,0,
184,Divergent Roles of Vascular Burden and Neurodegeneration in the Cognitive Decline of Geriatric Depression Patients and Mild Cognitive Impairment Patients,"Both geriatric depression and mild cognitive impairment (MCI) confer an increased risk for the development of dementia. The mechanisms underlying the development of cognitive impairment in geriatric depression patients remain controversial. The present study aimed to explore the association of cognitive decline with vascular risk, white matter hyperintensity (WMH) burden and hippocampal volume in both remitted geriatric depression (RGD) subjects and amnestic mild cognitive impairment (aMCI) subjects. Forty-one RGD subjects, 51 aMCI subjects, and 64 healthy elderly subjects underwent multimodal MRI scans and neuropsychological tests at both baseline and a 35-month follow-up. According to the changing patterns (declining or stable) of global cognitive function during the follow-up period, each group was further divided into a declining subgroup and a stable subgroup. The Framingham 10-year cardiovascular risk, WMH volume and hippocampal volume were measured to assess vascular pathology and neurodegeneration, respectively. The RGD declining group displayed a higher vascular risk and greater WMH volume than the RGD stable group, whereas no such difference was found in the aMCI subjects. In contrast, the aMCI declining group displayed a smaller left hippocampal volume than the aMCI stable group, whereas no such difference was found in the RGD subjects. Furthermore, greater increases in the WHM volume correlated with greater decreases in global cognitive function in the RGD declining group, and greater decreases in the left hippocampal volume correlated with greater decreases in global cognitive function in the aMCI declining group. In conclusion, the cognitive decline in RGD patients is associated with vascular burden, whereas the cognitive decline in aMCI patients is associated with neurodegeneration. These findings could contribute to a better understanding of the specific mechanisms of the development of dementia in each condition.",cognitive decline;geriatric depression;hippocampal volume;mild cognitive impairment;vascular risk;white matter hyperintensity,"Ye, Q.;Su, F.;Gong, L.;Shu, H.;Liao, W.;Xie, C.;Zhou, H.;Zhang, Z.;Bai, F.",2017,,,0,
185,Effects of amyloid and vascular markers on cognitive decline in subcortical vascular dementia,"OBJECTIVE: To determine the independent and synergistic effects of amyloid and small vessel disease (SVD) burden on longitudinal cognitive decline in patients with subcortical vascular dementia (SVaD). METHODS: A longitudinal cohort study was conducted involving patients from outpatient clinics of 2 tertiary referral centers. Sixty-one patients with SVaD were prospectively recruited and underwent MRI, 11C-Pittsburgh compound B (PiB) PET at baseline, and a 3-year annual neuropsychological follow-up. Effects of PiB positivity and SVD markers (white matter hyperintensities [WMH], lacunes, and microbleeds) on longitudinal cognitive decline were evaluated using generalized estimation equation after controlling for age, sex, education, APOE4 allele, and follow-up interval. RESULTS: When individual neuropsychological tests were used as outcome measures, PiB positivity was associated with faster cognitive decline in attention, visuospatial, visual memory, and global cognition function. Higher WMH burden was associated with faster cognitive decline in attention, visuospatial, visual recognition memory, and semantic/phonemic fluency function, whereas lacunes and microbleeds had no significant effects. When global dementia rating (Clinical Dementia Rating sum of boxes) was considered as an outcome measure, however, only PiB positivity was associated with faster cognitive decline. Significant interactions between PiB positivity and higher SVD burden were found to affect cognitive decline in semantic word fluency (from WMH burden) and global dementia rating (from microbleed burden). CONCLUSIONS: In SVaD patients, amyloid burden, independently or interactively with SVD, contributed to longitudinal cognitive decline. Amyloid deposition was the strongest poor prognostic factor.","Aged;Aged, 80 and over;Amyloid/*metabolism;Amyloid beta-Peptides/*metabolism;Cognition Disorders/*diagnosis/*metabolism;Cohort Studies;Dementia, Vascular/*diagnosis/*metabolism;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging/trends;Male;Middle Aged;Prospective Studies","Ye, B. S.;Seo, S. W.;Kim, J. H.;Kim, G. H.;Cho, H.;Noh, Y.;Kim, H. J.;Yoon, C. W.;Woo, S. Y.;Kim, S. H.;Park, H. K.;Kim, S. T.;Choe, Y. S.;Lee, K. H.;Kim, J. S.;Oh, S. J.;Kim, C.;Weiner, M.;Lee, J. H.;Na, D. L.",2015,Nov 10,10.1212/wnl.0000000000002097,0,
186,"Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in cognitively impaired patients","BACKGROUND: We investigated the independent effects of Alzheimer's disease (AD) and cerebrovascular disease (CVD) pathologies on brain structural changes and cognition. METHODS: Amyloid burden (Pittsburgh compound B [PiB] retention ratio), CVD markers (volume of white matter hyperintensities [WMH] and number of lacunae), and structural changes (cortical thickness and hippocampal shape) were measured in 251 cognitively impaired patients. Path analyses were utilized to assess the effects of these markers on cognition. RESULTS: PiB retention ratio was associated with hippocampal atrophy, which was associated with memory impairment. WMH were associated with frontal thinning, which was associated with executive and memory dysfunctions. PiB retention ratio and lacunae were also associated with memory and executive dysfunction without the mediation of hippocampal or frontal atrophy. CONCLUSIONS: Our results suggest that the impacts of AD and CVD pathologies on cognition are mediated by specific brain regions.","Aged;Aged, 80 and over;Amyloid/*metabolism;Aniline Compounds/pharmacokinetics;Atrophy/etiology;Brain/*pathology/radionuclide imaging;Cerebrovascular Disorders/*complications/radionuclide imaging;Cognition Disorders/*complications/metabolism/*pathology/radionuclide imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Positron-Emission Tomography;Retrospective Studies;Thiazoles/pharmacokinetics;Amyloid;Atrophy;Cerebrovascular disease;Cognition;Cortical thickness;Hippocampus;Path analysis;Pittsburgh compound B","Ye, B. S.;Seo, S. W.;Kim, G. H.;Noh, Y.;Cho, H.;Yoon, C. W.;Kim, H. J.;Chin, J.;Jeon, S.;Lee, J. M.;Seong, J. K.;Kim, J. S.;Lee, J. H.;Choe, Y. S.;Lee, K. H.;Sohn, Y. H.;Ewers, M.;Weiner, M.;Na, D. L.",2015,May,10.1016/j.jalz.2014.04.521,0,
187,Incidence of cerebral microbleeds in preclinical Alzheimer disease,"OBJECTIVE: We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with (11)C-Pittsburgh compound B (PiB) PET imaging. METHODS: One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and (11)C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB+/-, standardized uptake value ratio >1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE epsilon4+ status, and cerebrovascular disease. RESULTS: LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p < 0.05 vs NC). LMB incidence was 0.2 +/- 0.6 per year in NC participants, 0.2 +/- 0.5 in MCI, and 0.7 +/- 1.4 in AD (p < 0.03 vs NC) and was 6-fold higher in PiB+ than PiB-NC. Incident LMBs were associated with age, APOE epsilon4+, PiB+, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity. CONCLUSIONS: Older age, baseline LMBs, higher beta-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/complications/ radionuclide imaging;Amyloid/ metabolism;Aniline Compounds;Australia;Brain/pathology/ radionuclide imaging;Cerebral Small Vessel Diseases/complications/ diagnosis;Female;Humans;Incidence;Intracranial Hemorrhages/complications/epidemiology/ radionuclide imaging;Magnetic Resonance Imaging/methods;Male;Middle Aged;Positron-Emission Tomography/methods;Thiazoles","Yates, P. A.;Desmond, P. M.;Phal, P. M.;Steward, C.;Szoeke, C.;Salvado, O.;Ellis, K. A.;Martins, R. N.;Masters, C. L.;Ames, D.;Villemagne, V. L.;Rowe, C. C.",2014,Apr 8,10.1212/wnl.0000000000000285,0,
188,Differential diagnosis of bilateral parietal abnormalities in I-123 IMP SPECT imaging,"This report discusses the clinical significance of bilateral parietal abnormalities on I-123 IMP SPECT imaging in 158 patients with cerebral disorders. This pattern was seen in 15 out of 21 patients with Alzheimer's disease; it was also seen in 4 out of 5 patients with Parkinson's disease with dementia, in 3 out of 17 patients with vascular dementia, in 1 out of 36 patients with cerebral infarction without dementia, in 1 out of 2 patients with hypoglycemia, and in 1 out of 2 patients with CO intoxication. Detection of bilateral parietal abnormalities is a useful finding in the diagnosis of Alzheimer's disease, but one should keep in mind that other cerebral disorders may also show a similar pattern with I-123 IMP SPECT imaging.",,"Yasuo, K.;Yuichi, I.;Makoto, O.;Takashi, T.;Toshimitsu, F.;Ranjan, G.;Kouji, M.",1990,1990,,0,
189,An autopsy case of bilateral carotid artery occlusion with repetitive epilepsy and brain atrophy in a senile patient,"A 67-year-old man was referred to us for tonic-clonic convulsions. A review of his history revealed that he had been hospitalized for loss of consciousness, hypotension, and suspected apoplexy at age 67. He had experienced prior tonic-clonic convulsions at age 72 and age 74. He had malaria and tuberculosis in his history but had been otherwise generally well. Physical examination was normal, and his blood pressure was 100/80 mmHg. Laboratory findings were normal except alcalinephosphatase (292 U/l) and gamma-glutamyl transpeptidase (60 U/l). Neurological examination showed alert consciousness, mild upper gaze palsy, slight right-side hemiparesis and left Babinski signs was present. Cranial magnetic resonance imaging showed no abnormality, but cerebral angiography revealed bilateral carotid artery occlusion. There were abundant leptomeningeal anastomoses, and the posterior communicating artery was supplied by the left vertebral artery. Electroencephalography showed a spike wave in the temporal lobe and rebuild- up phenomenon in the right hemisphere. Brain atrophy in the anterior and temporal lobes progressed, and the patient experienced gradual disorientation, delirium and hypobulia. He was eventually bedridden. He also demonstrated repetitive tonic-clonic convulsions. After one convulsion, he remained unconscious and died of pneumonia. Autopsy revealed thickening of the intima and internal elastic lamina in the occluded internal carotid artery. The anterior and middle cerebral arteries showed the same pathological changes. Multiple small infarctions restricted to grey matter were present in the cerebral cortex and may have caused the progressive brain atrophy. There was no myelin pallor in the white matter of the cerebrum. Atherosclerotic changes, senile plaque, and neurofibrillary tangles were seen but were within normal limits. These pathological findings were strongly suggestive of moyamoya disease.",,"Yasui, K.;Ito, Y.;Ando, T.;Yanagi, T.;Tsuzuki, T.;Yoshida, M.;Hashizume, Y.;Sobue, G.",2000,2000,,0,
190,Searching for novel biomarkers using high resolution diffusion tensor imaging,"Diffusion tensor imaging is capable of resolving large fiber bundles (e.g. the corpus callosum) and has been quite informative in understanding the overall structural connectivity of the brain. Recent data has shown that traditional resolution limitations can be exceeded in humans in vivo to submillimeter resolution. This chapter discusses these new techniques, and specific applications to small pathways such as the perforant path in the medial temporal lobe. High-resolution diffusion tensor imaging is a promising new tool that can be used to discover novel biomarkers for Alzheimers disease and other disorders. It allows for a much more detailed investigation of brain white matter than previously possible, perhaps offering clues into the first signs of synaptic deterioration that may precede frank neuronl loss. Although these methods are still in their infancy and many challenges have to be overcome before they can be used in a clinical fashion, results so far have been promising. Challenges and future directions are discussed in detail. © 2011 IOS Press and the authors. All rights reserved.",,"Yassa, M. A.",2011,2011,,0,
191,Diffusion abnormalities of the uncinate fasciculus in Alzheimer's disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract,INTRODUCTION: Our aim was to determine diffusion abnormalities in the uncinate fasciculus (UF) in Alzheimer's disease (AD) by diffusion tensor tractography (DTT) using a new method for measuring the core of the tract. METHODS: We studied 19 patients with AD and 19 age-matched control subjects who underwent MRI using diffusion tensor imaging (DTI). DTT of the UF was generated. The mean diffusivity (MD) and fractional anisotropy (FA) of the core of the tract were measured after voxelized tract shape processing. Student's t-test was used to compare results between patients with AD and controls. Intraobserver correlation tests were also performed. RESULTS: FA was significantly lower (P < 0.0001) in the UF of patients with AD than of controls. There was no significant difference in MD along the UF between the two groups. Intraobserver reliability (intraclass correlation coefficient) for the first and second measurement was r > 0.93 for measured FA and r > 0.92 for measured MD. CONCLUSION: Our results suggest that FA reflects progression of AD-related histopathological changes in the UF of the white matter and may represent a useful biological index in monitoring AD. Diffusion tensor tract-specific analysis with voxelized tract shape processing to measure the core of the tract may be a sensitive tool for evaluation of diffusion abnormalities of white matter tracts in AD.,"Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/metabolism;Anisotropy;Diffusion;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Pyramidal Tracts/metabolism/ pathology;Reproducibility of Results;Temporal Lobe/metabolism/ pathology","Yasmin, H.;Nakata, Y.;Aoki, S.;Abe, O.;Sato, N.;Nemoto, K.;Arima, K.;Furuta, N.;Uno, M.;Hirai, S.;Masutani, Y.;Ohtomo, K.",2008,Apr,10.1007/s00234-007-0353-7,0,
192,The clinical and neuroimaging features of neuronal ceroid lipofuscinosis,"Objective: To study the clinical and neuroimaging features of neuronal ceroid lipofuscinosis (NCL) in China. Methods: Clinical and radiological data of 11 cases of NCL confirmed by pathology in our institution were retrospectively analyzed and compared with those of 15 cases of NCL reported in Chinese literature. Results: Twelve cases of 26 patients were juvenile NCLs, was accounting for 46% of all the NCL cases. Most of the onset began at 3-15 years old, with the symptoms of mental retardation and seizures. Eight late infantile NCLs accounted for 31% of the NCLs, who began with seizures at ages of 1-7 years. Four infantile NCLs accounted for 15% of all cases, who presented with progressive motor and mental retardation beginning from 4-9 months old. Two adult NCLs, accounting for 8% , showed dementia and psychiatric symptoms beginning at the age of 26 and 32 years. MRI was characterized by diffuse brain atrophy. Some cases showed white matter impairment. Thalamus was involved in infantile NCL and late infantile NCL Conclusions: In this study, the most common form of NCL is juvenile NCL. The clinical symptoms and course of the disease differ between the subgroups. The radiological manifestations are similar, except that thalamus is involved in infantile NCL and late infantile NCL.",adolescent;adult;article;brain atrophy;child;China;clinical article;clinical feature;controlled study;dementia;disease course;histopathology;human;juvenile;medical literature;mental deficiency;mental disease;motor retardation;neuroimaging;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;onset age;retrospective study;seizure;thalamus;white matter,"Yao, S.;Bi, H. Y.;Lü, H.;Zhang, W.;Wang, Z. X.;Xiao, J. X.;Yuan, Y.",2006,,,0,
193,Hippocampal perivascular spaces are related to aging and blood pressure but not to cognition,"The risk factors of hippocampal dilated perivascular spaces (H-dPVS), their radiological relevance and their impact on cognitive performance remain under investigation. These aspects were evaluated in 1818 stroke- and dementia-free participants enrolled in the 3C-Dijon MRI study, using logistic regression, multiple linear regression, and Cox models. At study entry, the load of H-dPVS was found strongly associated with age and hypertension (degree 2 vs. degree 0: odds ratio: 1.16; 95% confidence interval: 1.02-1.33 and odds ratio: 1.98; 95% confidence interval: 1.39-2.81, respectively) and positively related to the presence of lacunar infarcts, white-matter hyperintensities volume, and hippocampal volume (p </= 0.024). Load of H-dPVS was not related to baseline cognitive performance (p > 0.05). Cox regression modeling did not show a significant relationship between the load of H-dPVS and incident dementia risk (p > 0.05). The present results support that both aging and blood pressure do play a key role in the development of H-dPVS in the older population. In contrast with the dilated perivascular spaces located in white matter or basal ganglia, the load of H-dPVS does not appear associated with occurrence of dementia.","Aged;Aged, 80 and over;Aging/*pathology;Blood Pressure/*physiology;Cognition;Cohort Studies;Dilatation, Pathologic;Female;Hippocampus/*pathology;Humans;Hypertension/*pathology/physiopathology;Logistic Models;Magnetic Resonance Imaging/methods;Male;Proportional Hazards Models;Risk Factors;Hippocampal dilated perivascular spaces;Mri","Yao, M.;Zhu, Y. C.;Soumare, A.;Dufouil, C.;Mazoyer, B.;Tzourio, C.;Chabriat, H.",2014,Sep,10.1016/j.neurobiolaging.2014.03.021,0,
194,Extensive white matter hyperintensities may increase brain volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: The extent of white matter hyperintensities (WMH) is associated with cerebral atrophy in elderly people. WMH is a radiological hallmark of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but their relationship with brain volume remains poorly understood. The association between WMH and brain volume was analyzed in a large population of patients with CADASIL. METHODS: Demographic and MRI data of 278 patients recruited from a prospective cohort study were analyzed. Volumes of WMH and lacunar infarcts, number of cerebral microbleeds, and brain parenchymal fraction were measured. Multivariate analysis was used to study the impact of WMH on brain volume at baseline. RESULTS: In univariate analyses, brain parenchymal fraction was negatively associated with age, male sex, and all MRI markers. Multiple regression modeling showed that brain parenchymal fraction was inversely related to age, number of cerebral microbleeds, and normalized volume of lacunar infarcts but positively related to normalized volume of WMH (P<0.001). This positive relationship was independent of the presence/absence of lacunar infarcts or of cerebral microbleeds. Subgroup analysis showed that this association was significant in subjects having normalized volume of WMH >/=6.13 or brain parenchymal fraction >/=86.37% (median values, both P</=0.001). CONCLUSIONS: The results of the present study suggest that extensive WMH may be associated with increase of brain volume in CADASIL. In this disorder, WMH may be related not only to loss of white matter components, but also to a global increase of water content in the cerebral tissue.","Adult;Age Factors;Aged;Atrophy;Brain/metabolism/*pathology;CADASIL/*pathology;Cerebral Hemorrhage/pathology;Female;Humans;Leukoencephalopathies/*pathology;*Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Stroke, Lacunar/*pathology;Water/metabolism;Young Adult","Yao, M.;Jouvent, E.;During, M.;Godin, O.;Herve, D.;Guichard, J. P.;Zhu, Y. C.;Gschwendtner, A.;Opherk, C.;Dichgans, M.;Chabriat, H.",2012,Dec,10.1161/strokeaha.112.664854,0,
195,Dilated perivascular spaces in small-vessel disease: A study in CADASIL,"Background and Aim: Dilated perivascular spaces (dPVS) have previously been associated with aging and hypertension-related cerebral microangiopathy. However, their risk factors, radiological features and clinical relevance have been poorly evaluated in CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a unique model to investigate the pathophysiology of ischemic small-vessel disease. The purpose of this study was to investigate these different aspects in a large cohort of patients with this disorder. Methods: Demographic and MRI data of 344 patients from a prospective cohort study were analyzed. The severity of dPVS was evaluated separately in the anterior temporal lobes, subinsular areas, basal ganglia and white matter, using validated semiquantitative scales. Logistic and multiple linear regression models were used to determine the risk factors associated with the severity of dPVS in these different regions and their relationships with cognition, disability and the MRI markers of the disease (white matter hyperintensities (WMH) lacunar infarcts, microbleeds and brain parenchymal fraction (BPF)). Results: The severity of dPVS was found to increase with age regardless of cerebral area (p < 0.001). In contrast with dPVS in other locations, the severity of dPVS in the temporal lobes or subinsular areas was also found strongly and specifically related to the extent of WMH (p < 0.001). Conversely, no significant association was detected with lacunar volume, number of microbleeds or BPF. A high degree of dPVS in the white matter was associated with lower cognitive performances independently of age and other MRI markers of the disease including BPF (p ≤ 0.04). Conclusions: In CADASIL, the progression of the hereditary microangiopathy with aging may promote the dilation of perivascular spaces throughout the whole brain but with variable extent according to cerebral location. In temporal lobes and subinsular areas, dPVS are common MRI features and may share a similar pathogenesis with the extension of WMH during the course of the disease. dPVS may also participate in the development of cognitive decline in this model of small-vessel disease, and their large number in white matter may alert clinicians to a higher risk of cognitive decline in CADASIL.",adult;age;aged;article;basal ganglion;brain hemorrhage;brain infarction;brain parenchymal fraction;brain region;CADASIL;cerebrovascular disease;clinical feature;cognition;cognitive defect;cohort analysis;demography;dilated perivascular space;disease severity;echo planar imaging;female;human;major clinical study;male;Mini Mental State Examination;nervous system parameters;nuclear magnetic resonance imaging;priority journal;prospective study;temporal lobe;vasodilatation;white matter;white matter hyperintensity;white matter injury,"Yao, M.;Hervé, D.;Jouvent, E.;Duering, M.;Reyes, S.;Godin, O.;Guichard, J. P.;Dichgans, M.;Chabriat, H.",2014,,,0,
196,NIHSS scores in ischemic small vessel disease: a study in CADASIL,"BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is widely used to measure neurological deficits, evaluate the effectiveness of treatment and predict outcome in acute ischemic stroke. It has also been used to measure the residual neurological deficit at the chronic stage after ischemic events. However, the value of NIHSS in ischemic cerebral small vessel disease has not been specifically evaluated. The purpose of this study was to investigate the link between the NIHSS score and clinical severity in a large population of subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a unique model to investigate the pathophysiology and natural history of ischemic small vessel disease. METHODS: Demographic and clinical data of 220 patients with one or more lacunar infarcts confirmed by MRI examination and enrolled from a prospective cohort study were analyzed. Detailed neurological examinations, including evaluation of the NIHSS and modified Rankin Scale score (mRS) for evaluating the clinical severity, were performed in all subjects. The sensitivity, specificity, positive and negative predictive values of various NIHSS thresholds to capture the absence of significant disability (mRS <3) were calculated. General linear models, controlling for age, educational level and different clinical manifestations frequently observed in CADASIL, were used to evaluate the relationships between NIHSS and clinical severity. RESULTS: In the whole cohort, 45 (20.5%) subjects presented with mRS >/=3, but only 16 (7.3%) had NIHSS >5. All but 1 subject with NIHSS >5 showed mRS >/=3. NIHSS </=5 had an 85.3% positive predictive value for no or slight disability with only 33.3% specificity. The NIHSS, MMSE score and presence or absence of gait disturbances were found to be strongly and independently correlated with disability (all p < 0.001). Altogether, they accounted for 73% of the variance of mRS in contrast with the NIHSS alone accounting for only 50% of this variance. Among patients with NIHSS </=5, subjects with mRS >/=3 showed a lower MMSE score than those with mRS <3 (p < 0.001). All patients with NIHSS </=5 but with mRS >/=3 presented either with gait disturbances or MMSE score <25. CONCLUSIONS: The present results suggest that the NIHSS cannot reflect the extent of neurological deficit and clinical severity in subjects with lacunar infarctions in the context of a chronic and diffuse small vessel disease. A specific and global neurological scale, including the assessment of cognitive and gait performances, should be developed for ischemic cerebral microangiopathy.",Adult;Aged;Brain Ischemia/*diagnosis;CADASIL/*diagnosis;Cerebral Small Vessel Diseases/*diagnosis;Cohort Studies;Disease Progression;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;National Institutes of Health (U.S.);Neuropsychological Tests;Prospective Studies;Sensitivity and Specificity;Severity of Illness Index;United States,"Yao, M.;Herve, D.;Allili, N.;Jouvent, E.;Duering, M.;Dichgans, M.;Chabriat, H.",2012,,10.1159/000345067,0,
197,Cerebral blood flow in nondemented elderly subjects with extensive deep white matter lesions on magnetic resonance imaging,"Our previous study showed that deep white matter lesions (DWML) were associated with subtle cognitive decline in community-dwelling elderly people. However, even extensive (EXT)-DWML, found in 7 (4%) of 178 subjects aged 60 years or older, did not cause dementia. The purpose of the present study was to investigate brain circulation in nondemented elderly subjects with EXT-DWML. We compared cerebral blood flow in the deep white matter and frontal cortex between 5 subjects with EXT-DWML and 5 without such lesions, using a xenon-enhanced computed tomography (CT) method. Although the difference of deep white matter findings on magnetic resonance imaging (MRI) was the greatest possible (i.e., extensive v no or minimum lesions), cerebral blood flow values in anterior deep white matter and frontal cortex were 21.4 +/- 5.3 standard deviation (SD) mL/100 g/minute and 42.7 +/- 4.1, respectively, in subjects with extensive lesions, which were not significantly different from 24.3 +/- 4.3 and 44.0 +/- 7.1 in subjects without DWML. The present study suggests that EXT-DWML in nondemented elderly individuals do not necessarily indicate apparent hypoperfusion or marked cognitive decline.",,"Yao, H.;Yuzuriha, T.;Fukuda, K.;Matsumoto, T.;Ibayashi, S.;Uchimura, H.;Fujishima, M.",2000,Jul-Aug,10.1053/jscd.2000.7218,0,
198,Hypertension and white matter lesions are independently associated with apathetic behavior in healthy elderly subjects: The Sefuri brain MRI study,"Apathy is defined as a syndrome of primary loss of motivation not attributable to emotional distress, intellectual impairment or consciousness disturbance. The aim of our study was to investigate the effects of vascular risk factors and silent ischemic brain lesions on apathetic behavior of community-dwelling elderly subjects. Brain MRI and other medical examinations were performed on 222 non-demented community-dwelling elderly subjects (96 men and 126 women, average age 70.1 years). The apathy group was defined as the most apathetic quintile determined by Starkstein's apathy scale. Silent infarction, deep white matter lesions (DWMLs) and periventricular hyperintensities were detected in 12.2, 39.2 and 22.5%, respectively. Linear regression analysis (Pearson) revealed that the scores on the apathy scale correlated slightly but significantly with logarithmically transformed scores of the Modified Stroop Test (r=0.135, P=0.045), but not with the Mini-Mental State Examination. The apathy group tended to have more high blood pressure (141.6/82.6 vs. 136.1/79.6mmHg), less prevalent hyperlipidemia (18 vs. 35%) and lower serum albumin. Multivariate analysis (the forward stepwise method of logistic analysis) revealed an independent correlation between the apathy and grade of DWMLs (odds ratio 1.826, 95% confidence interval (CI) 1.129-2.953 per grade) or diastolic blood pressure (DBP) (odds ratio 1.055, 95% CI 1.014-1.098 per mmHg) after adjusting for possible confounders. The mean apathy scale score in the DBP ≧ 90mmHg group was significantly lower (more apathetic) than that in the DBP < 80 group (P=0.011, analysis of covariance). This study showed that hypertension and DWMLs are independently associated with apathy in healthy elderly subjects.",albumin;aged;albumin blood level;apathy;article;brain infarction;brain ischemia;diastolic blood pressure;disease association;disease severity;female;human;hyperlipidemia;hypertension;image analysis;major clinical study;male;neuropathology;nuclear magnetic resonance imaging,"Yao, H.;Takashima, Y.;Mori, T.;Uchino, A.;Hashimoto, M.;Yuzuriha, T.;Miwa, Y.;Sasaguri, T.",2009,,,0,
199,Subclinical cerebral abnormalities in chronic kidney disease,"BACKGROUND AND PURPOSE: Impaired kidney function or chronic kidney disease (CKD), as measured by estimated glomerular filtration rate (eGFR), is associated with incident stroke risk. However, few studies have examined the relationship between CKD and subclinical cerebral abnormalities. METHODS: We examined 675 elderly subjects (mean age 69.9 years), who were living independently at home without apparent dementia, using magnetic resonance imaging. Serum creatinine values, measured by the enzymatic method, were used for the Japanese equation of eGFR. RESULTS: Subclinical lacunar infarction, deep white matter lesions, and periventricular hyperintensities were detected in 88 (13.0%), 240 (35.6%) and 158 (23.4%) of the 675 participants, respectively. In the forward stepwise method of logistic analysis, age (OR 2.081/10, 95% CI 1.541-2.810), hypertension (OR 3.656, 95% CI 2.184-6.119), diabetes mellitus (OR 1.961, 95% CI 1.007-3.820), alcohol intake (OR 2.130, 95% CI 1.283-3.535), and eGFR <45 ml/min/1.73 m(2) were significant factors concerning subclinical lacunar infarction. CKD defined as eGFR <60 ml/min/1.73 m(2) was not significantly associated with subclinical lacunar infarction. Decreased eGFR was not a significant factor associated with white matter lesions (WMLs). Age (OR 2.781/10, 95% CI 2.252-3.435), hypertension (OR 1.746, 95% CI 1.231-2.477), diabetes mellitus (OR 1.854, 95% CI 1.070-3.213), but not eGFR were significant factors concerning WMLs. CONCLUSIONS: The present study showed that community-dwelling elderly subjects with late stage 3 CKD were at high risk for prevalent subclinical lacunar infarction. The identification of CKD-specific modifiable risk factors for SBI and WMLs is of increased importance for prevention of subclinical brain ischemic lesions.","Age Factors;Aged;Aged, 80 and over;Alcohol Drinking/epidemiology;Atrial Fibrillation/epidemiology;Brain/ pathology;Brain Ischemia/prevention & control;Comorbidity;Creatinine/blood;Cross-Sectional Studies;Diabetes Mellitus/blood/epidemiology;Dyslipidemias/blood/epidemiology;Female;Glomerular Filtration Rate;Humans;Hypertension/epidemiology;Hypertrophy, Left Ventricular/epidemiology;Independent Living;Japan/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Prevalence;Renal Insufficiency, Chronic/blood/ epidemiology/pathology;Sampling Studies;Smoking/epidemiology;Stroke, Lacunar/ epidemiology/pathology","Yao, H.;Takashima, Y.;Hashimoto, M.;Uchino, A.;Yuzuriha, T.",2013,,10.1159/000346719,0,
200,Leisure-Time Physical Inactivity Associated with Vascular Depression or Apathy in Community-Dwelling Elderly Subjects: The Sefuri Study,"BACKGROUND: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM). METHODS: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities). RESULTS: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (beta = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects. CONCLUSIONS: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life.",,"Yao, H.;Takashima, Y.;Araki, Y.;Uchino, A.;Yuzuriha, T.;Hashimoto, M.",2015,Nov,10.1016/j.jstrokecerebrovasdis.2015.07.018,0,
201,Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type,"We performed clinical and neuroradiologic studies, including positron emission tomography, in five patients with vascular dementia of the Binswanger type. The clinical features of these cases consisted of slowly progressive dementia, together with vascular risk factors such as hypertension and often a history of minor stroke, and characteristic white matter lesions on brain computed tomograms or magnetic resonance images. Digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient. Both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter (54-77% of control values), and both were decreased in the parietal (73% of control), frontal (74-80%), and temporal (74-83%) cortices, where no abnormalities were detected by brain computed tomography or magnetic resonance imaging. We conclude that vascular dementia of the Binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter.","Aged;Cerebrovascular Circulation;Dementia/diagnosis/ metabolism/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Oxygen Consumption;Tomography, Emission-Computed;Tomography, X-Ray Computed","Yao, H.;Sadoshima, S.;Kuwabara, Y.;Ichiya, Y.;Fujishima, M.",1990,Dec,,0,
202,Chronic kidney disease and subclinical lacunar infarction are independently associated with frontal lobe dysfunction in community-dwelling elderly subjects: the Sefuri brain MRI study,"Although recent studies have found that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment in population-based cohorts, the mechanisms of cognitive impairment in subjects with CKD are unclear. We examined 503 elderly subjects (mean age: 72.4 years), who were living independently at home without apparent dementia, using MRI. The subject was judged as having frontal lobe dysfunction if the scores on the modified Stroop test were higher than the fifth quintile for each given decade. Serum creatinine values, measured by the enzymatic method, were used for the Japanese equation of estimated glomerular filtration rate (eGFR). Subjects in the frontal lobe dysfunction group tended to have higher blood pressure, lower eGFR and more lacunar infarcts, and were less educated. When possible confounders were entered into the multivariate logistic regression model, the independent predictors of frontal lobe dysfunction were eGFR (odds ratio 0.854; 95% confidence interval (CI) 0.743-0.983 per 10 ml min(-1) per 1.73 m(2)) and the number of lacunar infarction (odds ratio 1.460; 95% CI 1.127-1.892). The mean of the logarithmically transformed Stroop test scores in the eGFR<60 ml min(-1) per 1.73 m(2) group was 1.376 (95% CI 1.301-1.451), which was significantly higher than that (1.250) for the eGFR 60-89 ml min(-1) per 1.73 m(2) group (95% CI 1.215-1.285) (P=0.009) and tended to be higher than that (1.264) for the eGFR >/=90 ml min(-1) per 1.73 m(2) group (95% CI 1.188-1.340) (analysis of covariance, adjusted for age). The present study showed that CKD and subclinical lacunar infarction independently contributed to frontal lobe dysfunction in healthy elderly subjects.","Aged;Aged, 80 and over;Creatinine/blood;Cross-Sectional Studies;Female;Frontal Lobe/*physiopathology;Glomerular Filtration Rate;Humans;Male;Middle Aged;Renal Insufficiency, Chronic/complications/*physiopathology;Stroke, Lacunar/etiology/*physiopathology;Stroop Test","Yao, H.;Miwa, Y.;Takashima, Y.;Yahara, K.;Hashimoto, M.;Uchino, A.;Yuzuriha, T.;Sasaguri, T.",2011,Sep,10.1038/hr.2011.83,0,
203,Cerebral blood flow and metabolism in silent brain infarction and related cerebrovascular disorders,"The appropriate management of silent stroke requires better understanding of the haemodynamic status in the brain. However, only a few studies have examined cerebral blood flow and metabolism in subjects with silent stroke. Positron emission tomography demonstrated a slight decrease in cortical blood flow with an increase in oxygen extraction fraction (ie misery perfusion) in subjects with silent brain infarction, whereas both cerebral blood flow and oxygen metabolism decreased in patients with symptomatic brain infarction (matched hypoperfusion). These findings confirm that brain circulation is haemodynamically compromised in subjects with silent stroke. Another important point is that subcortical silent stroke may induce a reduction in cortical blood flow and metabolism by a disconnection mechanism (ie diaschisis) between the cortex and the subcortical structures. Silent infarction is not innocuous in terms of compromised cerebral circulation, which may lead to cognitive decline or subsequent clinical stroke. In the future, further developments in functional imaging will permit a more sophisticated analysis of brain circulation and metabolism in silent stroke.",,"Yao, H.;Fujishima, M.",2001,2001,,0,
204,Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study,"BACKGROUND AND PURPOSE: The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. METHODS: We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. RESULTS: Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (beta = -.10, P = .027, and beta = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (beta = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (beta = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. CONCLUSIONS: Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.",Small vessel disease;executive function;glomerular filtration rate;magnetic resonance imaging;silent stroke;vascular cognitive impairment,"Yao, H.;Araki, Y.;Takashima, Y.;Uchino, A.;Yuzuriha, T.;Hashimoto, M.",2017,Feb,,0,
205,Structural MRI biomarkers of mild cognitive impairment from young elders to centenarians,"Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. Methods - 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain “atrophy” and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were per- formed to determine structures that best discriminated aMCI from CN in individuals <85 and those ≥85 years. Results - aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortices in <85 years, and the hippocampus, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes. Conclusions - Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly in- dividuals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.",biological marker;aged;article;brain atrophy;brain cortex;female;frontal cortex;human;image analysis;image processing;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;parahippocampal gyrus;precuneus;priority journal;putamen;very elderly;Philips 3T Achieva Quasar Dual Scanner,"Yang, Z.;Wen, W.;Jiang, J.;Crawford, J. D.;Reppermund, S.;Levitan, C.;Slavin, M. J.;Kochan, N. A.;Richmond, R. L.;Brodaty, H.;Trollor, J. N.;Sachdev, P. S.",2016,,,0,
206,Age-associated differences on structural brain MRI in nondemented individuals from 71 to 103 years,"Successful brain aging in the oldest old (≥90 years) is underexplored. This study examined cross-sectional brain morphological differences from 8th to 11th decades of life in nondemented individuals by high-resolution magnetic resonance imaging. Two hundred seventy-seven nondemented community-dwelling participants (71-103 years) from Sydney Memory and Ageing Study and Sydney Centenarian Study comprised the sample, including a subsample of 160 cognitively high-functioning elders. Relationships between age and magnetic resonance imaging-derived measurements were studied using general linear models; and structural profiles of the ≥90 years were delineated. In full sample and the subsample, significant linear negative relationship of gray matter with age was found, with the greatest age effects in the medial temporal lobe and parietal and occipital cortices. This pattern was further confirmed by comparing directly the ≥90 years to the 71-89 years groups. Significant quadratic age effects on total white matter and white matter hyperintensities were observed. Our study demonstrated heterogeneous differences across brain regions between the oldest old and young old, with an emphasis on hippocampus, temporoposterior cortex, and white matter hyperintensities.",,"Yang, Z.;Wen, W.;Jiang, J.;Crawford, J. D.;Reppermund, S.;Levitan, C.;Slavin, M. J.;Kochan, N. A.;Richmond, R. L.;Brodaty, H.;Trollor, J. N.;Sachdev, P. S.",2016,1,,0,
207,Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer,"BACKGROUND: Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid beta. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. METHODS: Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. RESULTS: Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. CONCLUSION: Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.","Animals;Brain/ blood supply;Cerebrospinal Fluid/ metabolism;Extracellular Fluid/metabolism;Female;Injections, Spinal;Intracranial Pressure;Lumbar Vertebrae/metabolism;Male;Mice, Inbred C57BL;Molecular Probes;Molecular Weight;Rats, Sprague-Dawley","Yang, L.;Kress, B. T.;Weber, H. J.;Thiyagarajan, M.;Wang, B.;Deane, R.;Benveniste, H.;Iliff, J. J.;Nedergaard, M.",2013,,10.1186/1479-5876-11-107,0,
208,Risk factors for incident dementia after stroke and transient ischemic attack,"BACKGROUND: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA). METHODS: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia. RESULTS: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively. CONCLUSIONS: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.","Age Factors;Aged;Aged, 80 and over;Aniline Compounds;Biomarkers/blood;Brain/blood supply/pathology/radionuclide imaging;Chronic Disease;Cohort Studies;Cross-Sectional Studies;Dementia/ etiology/pathology/radionuclide imaging;Diabetes Mellitus/pathology;Female;Humans;Ischemic Attack, Transient/ complications/pathology;Male;Middle Aged;Neuroimaging/methods;Positron-Emission Tomography/ methods;Radiopharmaceuticals;Risk Factors;Severity of Illness Index;Stroke/ complications/pathology;Temporal Lobe/pathology/radionuclide imaging;Thiazoles;White Matter/pathology/radionuclide imaging","Yang, J.;Wong, A.;Wang, Z.;Liu, W.;Au, L.;Xiong, Y.;Chu, W. W.;Leung, E. Y.;Chen, S.;Lau, C.;Chan, A. Y.;Lau, A. Y.;Fan, F.;Ip, V.;Soo, Y.;Leung, T.;Ho, C. L.;Wong, L. K.;Mok, V. C.",2015,Jan,10.1016/j.jalz.2014.01.003,0,
209,Logistic regression analysis on risk factors for vascular dementia following cerebral infarction in 403 patients from Chongqing City. Hospital and family follow-up studies,"Background: Studies have demonstrated that the risk factors of vascular dementia following stroke are greatly different in region, race and other aspects. Objective: To analyze the conditions and incidental risk factors of vascular dementia in patients with acute cerebral infarction from Chongqing City. Design: Case analysis. Setting: Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA. Participants: Altogether 546 inpatients with acute ischemic stroke admitted to Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA between May 1999 and December 2002 were involved in this study. The involved patients, including 295 males and 251 females, aged 55-94 years, dwelled in Chongqing over 5 years. They were admitted to hospital within 48 hours of attack of acute ischemic stroke, and survived for over 3 months. Informed consents were obtained from all the involved subjects. Methods: 1 Following the same standard, cognitive and social function evaluations were conducted by one physician on admission and 3 months after admission. Unified questionnaire, consisting of general characteristics, vascular risk factors, stroke characteristics, neurological physical sign, and other 28 factors of involved subjects, was used in all the patients. According to the investigation results, the patients were assigned into 2 groups: dementia group and non-dementia group. 2 Ischemic stroke was diagnosed according to acute ischemic brain disorder > 24 hours and CT or MRI imageology. 3 Neurophysiological examination was conducted in all the patients at 7 to 10 days after stroke (score was two SD less than or equaled to normal level was considered as abnormal). 4 Diagnosis and statistics of dementia were carried out with Mini-Mental State Examination and The Diagnostic and Statistical Manual of Mental Disorders-IV (published by American Psychiatric Association) on admission and 3 months after admission. Neurologic deficit scoring was carried out with the National Institutes of Health Stroke Scale. 5 Chi-square test was used for categorical variable, and t test for quantitative variable between dementia group and non-dementia group. Dementia-related factors were performed multiple-factor Logistic regression model analysis. Main Out Measures: Incidence of dementia and dementia-related risk factors of patients. Results: Altogether 546 patients with stroke were involved in this study, 403 of them participated in the final analysis, and 143 dropped out. A total of 342 were followed-up in the hospital and 61 at home. At 3 months after cerebral infarction, vascular dementia occurred in 87 (21.6%) of 403 patients. The main risk factors were age (OR 1. 179; 95%CI 1.130-1.230), low education level (OR 1.806; 95%CI 1.024-3.186), daily alcohol drinking (OR 3.447; 95%CI 1.591-7.468), stroke history (OR 2,531; 95%CI 1.419-4.512), atrial fibrilation(OR 3.475; 95%CI 1.712-7.057), dysphonia (OR 5.873; 95%CI 2.620-13.163) and left carotid artery infarction (OR 1.975; 95%CI 1.152-3.388). Conclusion: The incidence of vascular dementia is determined by synthetic action of multiple risk factors. Dysphonia is the most important influencing factor.",,"Yang, H.;Li, J.;Zhou, H.",2007,June,,0,
210,Analysis of cerebral blood flow of subcortical vascular dementia with single photon emission computed tomography: adaptation of statistical parametric mapping,"BACKGROUND AND OBJECTIVES: Subcortical vascular dementia (VaD) is a relatively homogeneous subtype of VaD, but the mechanisms of cognitive dysfunction of subcortical VaD are not fully understood. This study investigates the changes of cerebral blood flow (CBF) in patients with subcortical VaD and the contribution of the white matter hyperintensity (WMHI) and clinical severity to CBF changes. METHODS: 99mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) was performed to measure the regional CBF and statistical parametric mapping SPM99 software was applied to automated and objective analysis of the SPECT image data. Twenty-three patients (12 male, 11 female) with mild to moderate dementia who met both the criteria of the DSM-IV and probable and possible NINDS-AIREN for VaD and had subcortical white matter changes and lacunar infarctions in brain MRI were evaluated against 17 normal control subjects (7 male, 10 female). The severity of the WMHI was measured by the semi-quantitative scale method proposed by Mantyla. The Clinical Dementia Rating scale measured the severity of dementia. RESULTS: SPM analysis of the SPECT image reveals significantly reduced regional CBF in the right thalamus, left caudate nucleus, cingulate, bilateral superior temporal, and left ventral subcallosal gyri in subcortical VaD patients compared to the normal controls (corrected P<0.001). Of four WMHIs, only the deep WMHI was associated with the small CBF reduction in the left superior temporal gyrus (uncorrected P<0.01). The reduction of the CBF according to the severity of dementia was noted in the anterior and posterior association areas (uncorrected P<0.01). CONCLUSIONS: Our study suggests that cognitive dysfunction of subcortical VaD may be related to the reduction of the CBF in the brain areas mentioned, which are probably not associated with the severity of periventricular WMHI and dementia.","Aged;Aging/physiology;Brain/pathology;Brain Mapping/ methods;Cerebrovascular Circulation/ physiology;Dementia, Vascular/pathology/ physiopathology/radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Sex Characteristics;Tomography, Emission-Computed, Single-Photon","Yang, D. W.;Kim, B. S.;Park, J. K.;Kim, S. Y.;Kim, E. N.;Sohn, H. S.",2002,Nov 15,,0,
211,The Abnormality of Topological Asymmetry between Hemispheric Brain White Matter Networks in Alzheimer's Disease and Mild Cognitive Impairment,"A large number of morphology-based studies have previously reported a variety of regional abnormalities in hemispheric asymmetry in Alzheimer's disease (AD). Recently, neuroimaging studies have revealed changes in the topological organization of the structural network in AD. However, little is known about the alterations in topological asymmetries. In the present study, we used diffusion tensor image tractography to construct the hemispheric brain white matter networks of 25 AD patients, 95 mild cognitive impairment (MCI) patients, and 48 normal control (NC) subjects. Graph theoretical approaches were then employed to estimate hemispheric topological properties. Rightward asymmetry in both global and local network efficiencies were observed between the two hemispheres only in AD patients. The brain regions/nodes exhibiting increased rightward asymmetry in both AD and MCI patients were primarily located in the parahippocampal gyrus and cuneus. The observed rightward asymmetry was attributed to changes in the topological properties of the left hemisphere in AD patients. Finally, we found that the abnormal hemispheric asymmetries of brain network properties were significantly correlated with memory performance (Rey's Auditory Verbal Learning Test). Our findings provide new insights into the lateralized nature of hemispheric disconnectivity and highlight the potential for using hemispheric asymmetry of brain network measures as biomarkers for AD.",Alzheimer's disease;connectome;diffusion tensor imaging;graph theory;hemispheric asymmetry;lateralization;mild cognitive impairment,"Yang, C.;Zhong, S.;Zhou, X.;Wei, L.;Wang, L.;Nie, S.",2017,,,0,
212,The 3-year course and outcome of patients with major depression and silent cerebral infarction,We retrospectively investigated the relationship between major depression and silent cerebral infarction (SCI) over a 3-year period in 64 patients older than 50 years of age with unipolar depression. All patients underwent magnetic resonance imaging (MRI) at their first admission for depression and were classified into groups based on the presence or absence of SCI. The number of admissions due to depression was greater in the SCI (+) group (N = 32) than in the SCI (-) group (N = 32) (P < 0.05). The incidences of delirium and neurological disorders were significantly higher in the SCI (+) group than in the SCI (-) group. Our findings suggest that patients with depression and SCI had a higher rate of hospitalization and were more likely to develop psychiatric and neurological disorders than patients with depression without SCI.,"Age of Onset;Aged;Aged, 80 and over;Cerebral Infarction/ diagnosis/epidemiology;Cerebrovascular Disorders/epidemiology;Comorbidity;Delirium/epidemiology;Dementia/epidemiology;Depressive Disorder/ diagnosis/epidemiology;Female;Hospitalization/statistics & numerical data;Humans;Incidence;Magnetic Resonance Imaging;Male;Middle Aged;Parkinson Disease/epidemiology;Prognosis;Retrospective Studies;Terminology as Topic","Yanai, I.;Fujikawa, T.;Horiguchi, J.;Yamawaki, S.;Touhouda, Y.",1998,Jan,,0,
213,Difference in MRI findings and risk factors between multiple infarction without dementia and multi-infarct dementia,"MRI findings and risk factors for vascular dementia were evaluated with multi-variate analysis in 96 multi-infarct patients without dementia and 40 multi-infarct patients with dementia (MID). Only subjects with small infarcts in the territory of the perforator artery or deep white matter were studied. The diagnosis of MID was diagnosed according to DMS-III criteria and Hachinski's ischemia score. Location and area of patchy high-intensity areas including small infarcts, the degree of periventricular high intensity (PVH), and the degree of brain atrophy were examined with MR images. Independent variables were: history of hypertension, diabetes mellitus, other complications; systolic and diastolic blood pressure, atherosclerotic index, hematocrit, history of smoking, level of education, and activities of daily life (ADL). Hayashi's quantification method II was used to analyze the data. The most significant correlation was found between history of hypertension and dementia (partial correlation coefficient: 0.39). Significant correlations were also found between ADL and dementia (0.32), between thalamic infarction and dementia (0.31), and between PVH and dementia (0.27). Age, brain atrophy index, and history of diabetes mellitus contributed little to dementia. The contribution to dementia did not differ significantly between right and left patchy high-intensity areas on MR images. Location of infarcts, except for bilateral thalamic infarcts and large PVH, contributed little to dementia. Thus it would be difficult to base a prediction of the prevalence of vascular dementia on MRI findings. However, both hypertension and ADL contribute to vascular dementia and both are treatable, which may be significant for the prevention of dementia.",,"Yanagisawa, M.;Kaieda, M.;Nagatsumi, A.;Terashi, A.",1995,Oct,,0,
214,Late-onset spinal form xanthomatosis without brain lesion: a case report,"BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase (CYP27A1) gene. Patients with typical CTX show neurological dysfunction including bilateral cataracts, paresis, cerebral ataxia, dementia, and psychiatric disorders, and magnetic resonance imaging (MRI) has revealed symmetrical lesions in the cerebellar white matter. CASE PRESENTATION: We report the case of a patient with late-onset spinal form CTX without brain lesion. He showed pyramidal tract signs, and impaired joint position and vibration sensation in the lower limbs. Cervical sagittal MRI demonstrated a longitudinally extensive white matter abnormality in the dorsal column of the C2-C7 spinal cord; however, a brain MRI revealed an absence of lesions, including in the cerebellar white matter. Genetic analysis of CYP27A1 revealed that the patient was compound heterozygous for p.Gln85Arg in exon 1, a novel mutation, and p.Arg405Gln in exon 7, a previously reported mutation. CONCLUSION: This is the first report of late-onset spinal form CTX without typical neurological symptoms, and the first report of p.Gln85Arg in CYP27A1. We speculate that spinal form CTX without brain lesion is a clinically and radiologically rare variation of CTX. Therefore, spinal xanthomatosis should be included in the differential diagnosis of chronic myelopathy even with late-onset and/or no other typical neurological findings.",,"Yanagihashi, M.;Kano, O.;Terashima, T.;Kawase, Y.;Hanashiro, S.;Sawada, M.;Ishikawa, Y.;Shiraga, N.;Ikeda, K.;Iwasaki, Y.",2016,,10.1186/s12883-016-0542-2,0,
215,Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning Two case reports and a review of the literature,"Introduction: Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. Patient Concerns and Diagnoses: We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Interventions and Outcomes: Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Conclusion: Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.",aged;apathy;brain disease;brain function;carbon monoxide intoxication;case report;cognitive defect;diagnosis;drug therapy;female;frontal lobe;gene expression;gene inactivation;hippocampus;human;hyperbaric oxygen therapy;hypokinesia;Mini Mental State Examination;nuclear magnetic resonance imaging;physician;rating scale;white matter lesion;acetylcholine;carbon monoxide;donepezil;endogenous compound;galantamine;nicotinic receptor;steroid,"Yanagiha, K.;Ishii, K.;Tamaoka, A.",2017,,10.1097/md.0000000000006125,0,
216,A case of difficulty for differential diagnosis between encephalitis and acute disseminated encephalomyelitis,"A seventy-four-male with disorientation and convulsion was transferred to this hospital after three days fever which was unknown origin. Because the examination of cerebrospinal fluid were; cell count 1,560/3 (N: L = 4:1), protein 305 mg/dl, sugar 91 mg/dl, he was treated as encephalitis. However, MRI of the 18th hospital day revealed bilateral thalamic lesion and disseminated white matter lesions, suggesting acute disseminated encephalomyelitis. He left dementia after treatment and transferred to another hospital. Since, it is difficult to make a differential diagnosis between encephalitis and acute disseminated encephalomyelitis, early establishment of diagnostic criteria for acute disseminated encephalomyelitis is required.",article;cell count;cerebrospinal fluid;controlled study;dementia;differential diagnosis;encephalitis;encephalomyelitis;female;human;major clinical study;male;nuclear magnetic resonance imaging;patient transport,"Yanagawa, Y.;Kiyozumi, T.;Okada, Y.;Ogawa, G.;Kaida, K.;Kamakura, K.",2006,,,0,
217,Analysis on correlation of white matter lesion and lacunar infarction with vascular cognitive impairment,"OBJECTIVE: To investigate the correlation of white matter lesion (WML) and lacunar infarction (LI) with vascular cognitive impairment. To investigate the correlation of cognitive changes of vascular dementia (VD) patients with lacunar infarction (LI) and white matter lesion (WML). METHODS: The clinical data of 60 cases of VD patients were evaluated and analyzed by combining with imageological findings and cognitive function assessment. RESULTS: Multiple LI and WML were negatively correlated with both mini-mental state examination (MMSE) scale scores (r = -0.401, P = 0.036) and clock drawing test (CDT) scale scores (r = -0.482, P = 0.028); the LI number in occipital lobe was negatively correlated with MMSE scores (r = 0.338, P = 0.048), the LI number in temporal lobe was negatively correlated with CDT scores (r = -0.235, P = 0.047), and the LI number in frontal lobe was negatively correlated with MoCA scores (r = -0.450, P = 0.039). CONCLUSION: All of LI location and number as well as WML are independent influencing factors of cognitive impairment of VD patients.",,"Yan, T.;Yu, J. R.;Zhang, Y. P.;Li, T.",2015,,,0,
218,Callosal atrophy in patients with lacunar infarction and extensive leukoaraiosis. An indicator of cognitive impairment,"BACKGROUND AND PURPOSE: It is unclear why only some patients with lacunar infarction and radiological evidence of diffuse white matter abnormalities have dementia. The purpose of this study is to investigate the value of callosal atrophy as an indicator of cognitive impairment. METHODS: We used magnetic resonance imaging to evaluate 11 right-handed male patients with lacunar infarction and extensive white matter hypodensities on computed tomography (8 with dementia and 3 without dementia). The midsagittal corpus callosum area on T1-weighted images was compared with the IQ determined by the Wechsler Adult Intelligence Scale. The relation between these parameters and cerebral oxygen metabolism measured with positron emission tomography was also evaluated in the 8 patients with dementia. RESULTS: All patients showed diffuse high-intensity areas in the bilateral hemispheric white matter on T2-weighted images. Compared with 19 age- and sex-matched right-handed normal control subjects, the patients had a significantly smaller callosal area. The severity of callosal atrophy, which varied from mild to severe, was significantly related to the total IQ. In the 8 demented patients, the total callosal area was significantly correlated with the mean level of oxygen metabolism in the cerebral white matter. CONCLUSIONS: In patients with lacunar infarction and diffuse white matter abnormalities, the presence of callosal atrophy may indicate cognitive impairment. Callosal atrophy may reflect the severity and extent of white matter damage associated with a decrease in oxygen metabolism, which may determine the severity of intellectual decline.","Adult;Aged;Analysis of Variance;Atrophy;Brain/metabolism/radionuclide imaging;Cerebral Infarction/metabolism/ pathology/ physiopathology;Cognition Disorders/diagnosis/ etiology;Corpus Callosum/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Oxygen Consumption;Tomography, Emission-Computed;Wechsler Scales","Yamauchi, H.;Fukuyama, H.;Ogawa, M.;Ouchi, Y.;Kimura, J.",1994,Sep,,0,
219,Neuroaxonal leukoencephalopathy with axonal spheroids,"A 51-year-old woman with no significant family history exhibited progressive presenile dementia followed by right-sided spastic hemiplegia and died 27 months after the onset of her illness. Brain MRI demonstrated a widespread abnormality in the cerebral deep white matter and corpus callosum. Neuropathologically, extensive destruction of axons and myelin and abundant axonal spheroids were found in the deep white matter, preferentially of the frontoparietal areas. The corpus callosum was also severely damaged. The cerebral cortex and subcortical U fibers remained intact. The pathological features were different among the lesions, reflecting the sequential degenerative processes of the white matter. This case is, to our knowledge, the third sporadic case of neuroaxonal leukoencephalopathy with axonal spheroids. Copyright © 2002 S. Karger AG, Basel.",adult;article;brain cortex;brain injury;case report;clinical feature;corpus callosum;death;family history;female;frontal lobe;hemiplegia;human;human tissue;laboratory test;leukoencephalopathy;myelin sheath;nerve fiber degeneration;neuropathology;nuclear magnetic resonance imaging;parietal lobe;presenile dementia;priority journal;single photon emission computer tomography;white matter,"Yamashita, M.;Yamamoto, T.",2002,,,0,
220,A case of primary progressive multiple sclerosis with onset of memory impairment,"We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS) presenting with chronic progressive memory impairment. From a couple of years prior to admission, she had developed impairment of her short-term memory. For example, she forgot her nephew's name, and spoke the same phrases again and again. She also sometimes forgot to turn off her gas stove and forgot things she bought in shops. Moreover, herm mental activity gradually decreased and she became apathetic. However, she did not note her memory impairment, and had no hallucinations. She was admitted to our hospital on 20 May, 2003 because donepezil had been ineffective for treating her memory impairment. Neurologically, she showed bilateral horizontal gaze nystagmus, mild limb ataxia on the left and mildly ataxic gait. Neuropsychological examinations showed mildly impaired cognitive function, e.g., MMSE 25/30, WAIS-R full IQ 69 and especially in verbal short memory, which may represent temporal lobe dysfunction. Moreover, Benton's visual memory test revealed marked visual short-term memory impairment, while impaired performance on a Kana picking up test suggested mild to moderate attention impairment, which could have represented frontal lobe dysfunction. Brain MRI showed multiple T2-high plaque lesions close to the bilateral lateral ventricles, and bilateral optic nerve lesions enhanced by gadolinium. Also, spinal cord MRI showed a gadolinium enhanced lesion at Th5 on the left. Cerebral spinal fluid (CSF) examination showed normal cell count and protein level, and undetectable oligoclonal bands (OCB), but an elevated IgG index (1.1, normal<0.85). Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally, indicating subclinical optic nerve lesions. She was thus diagnosed as having PPMS according to McDonald's diagnostic criteria for MS. 99mTc Single photon emission computed tomography (SPECT) showed a decreased cerebral blood flow (CBF) in the bilateral frontal and temporal lobes, which was consistent with her clinical features. PPMS patients generally present with chronic progressive spastic paraparesis and/or cerebellar ataxia. Cognitive impairments observed in PPMS are generally thought to be due to white matter lesions, i.e., subcortical dementia. However, some recent reports have shown MS patients with short-term memory impairment (antegrade amnesia) similar to cortical dementias such as Alzheimer's disease (AD). In such MS cases, visual short-term memory impairment seems characteristic of their cognitive impairment compared to AD cases. As well, the present case showed visual memory impairment as evaluated by Benton's memory test. Parietal and frontal lobes are reported to be important for verbal and visual working memory, respectively. Thus, in the present case, decreased CBF in the frontal and temporal lobes, which could have been due to a disconnection between cortices and subcortices caused by the white matter lesions, is consistent with the type of her cognitive dysfunction, i.e., notable visual memory impairment. PPMS may thus be an important disease as a differential diagnosis for chronic progressive dementia. Further neuropsychological and functional imaging studies will be necessary to achieve a better understanding of the mechanisms of cognitive impairment in PPMS.",,"Yamashita, K. I.;Nomura, T.;Ohyagi, Y.;Taniwaki, T.;Furuya, H.;Kuwabara, Y.;Kira, J. I.",2005,May,,0,
221,Correlation between carotid blood flow and brain atrophy in patients with multi-infarct dementia,"The relation between carotid blood flow measured by Doppler spectrum analysis and brain atrophy on computed tomography (CT) was studied in 22 subjects with multiple lacunar cerebral infarctions. The subjects were divided into two groups, 7 patients with multi-infarct dementia (MID) (mean age 73 years) and 15 nondemented lacunar stroke subjects (NDLS) (mean age 66 years), according to DSM III criteria. All subjects had a score of 7 points or more on Hachinski's ischemic score and showed no carotid artery stenosis. Systolic peak frequency of the common carotid artery (CCA) was measured by Doppler spectrum analysis (Angioscan II). Brain atrophy was measured quantitatively on CT images by two-dimensional measurement using a digitizer. Peak frequencies were lower in MID than in NDLS. Brain atrophy was more severe in MID than in NDLS. There was a significant correlation between peak frequencies and brain atrophy in all subjects. These results indicate that CCA blood flow may reflect brain function in patients with multiple lacunar infarctions.","Aged;Aged, 80 and over;Atrophy;Brain/ pathology/physiopathology;Carotid Arteries/ physiopathology;Cerebrovascular Disorders/physiopathology;Dementia, Multi-Infarct/ physiopathology;Female;Humans;Male;Middle Aged;Regional Blood Flow;Rheology;Tomography, X-Ray Computed","Yamashita, K.;Kobayashi, S.;Yamaguchi, S.;Kitani, M.;Okada, K.;Fujihara, S.;Shimode, K.;Tsunematsu, T.",1989,,,0,
222,[The relationship between P300 latency and regional cerebral blood flow in patients with cerebral infarction in the territory of the deep perforators],"We studied the relationship between P300 latency and regional cerebral blood flow (rCBF) in nondemented patients with cerebral infarction. Subjects were 24 nondemented patients (mean age 64.1 years) who had a CT-proven infarct in the territory of the deep perforators of the internal carotid artery system and 53 controls (mean age 64.1 years). Prolongation of P300 latency with advancing age was observed in the both groups. There was no significant difference in P300 latency and rCBF between the two groups. There was a negative correlation between P300 latency and rCBF, especially in the bilateral fronto-parietal regions in the patient group. These results indicate that cognitive function assessed by P300 latency may be related to rCBF in the fronto-parietal region in the nondemented patients with lacunar infarctions.","Aged;Aged, 80 and over;Brain/*physiopathology;Cerebral Infarction/*physiopathology;*Cerebrovascular Circulation;Cognition;Dementia, Multi-Infarct/physiopathology;Evoked Potentials;Female;Humans;Male;Middle Aged","Yamashita, K.;Kobayashi, S.;Okada, K.;Koide, H.;Tsunematsu, T.",1991,Apr,,0,
223,"The relationship between cerebral white matter changes, mental function and blood pressure in normal elderly","The authors examined the relationship between cerebral white matter changes and mental function, blood pressure in 39 neurologically normal aged (21 males, 18 females, mean age 75.0 years) who had no latent lesions on MRI images. The severity of cerebral white matter changes was estimated by T1 value images on MRI and was measured in the bilateral frontal lobe on an axial slice at the level of the basal ganglia and in the bilateral anterior, middle, and posterior portions on axial slices at the level of the body of the lateral ventricle. Mental function was measured by the Hasegawa's dementia rating scale (HDS) and Kohs' block design test (Kohs' test). The severity of cerebral frontal white matter changes increased significantly with age (p less than 0.05). However there was no significant correlation between the severity of cerebral white matter changes and HDS, Kohs' test. The severity of frontal white matter changes correlated with the mean arterial blood pressure (p less than 0.02). These results suggest that the severity of cerebral white matter changes is not related with mental function in the normal elderly, and that the severity of frontal white matter lesions is related with mean arterial blood pressure.",Adult;Aged;Aging/pathology;Blood Pressure/ physiology;Brain/ pathology;Brain Diseases/pathology/physiopathology/ psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Psychological Tests,"Yamashita, K.;Kobayashi, S.;Fukuda, H.;Koide, H.;Okada, K.;Tsunematsu, T.",1991,Jul,,0,
224,Long-term prognosis of patients with major depression and silent cerebral infarction,"Objective: Many studies have examined the effects of cerebrovascular changes on treatment response in geriatric depression. However, few such studies have examined the relationship between cerebrovascular changes and long-term prognosis. We examined the effects of cerebrovascular changes on the course of geriatric depressive symptoms, dementia rates, and mortality over a follow-up period of approximately 10 years. Method: Participants were 84 patients with major depression (age of onset over 50 years); patients suffering from strokes, neurological disorders, and other psychiatric disorders were excluded. Magnetic resonance imaging findings were used to classify all patients into silent cerebral infarction (SCI)-positive (n = 37) or SCI-negative groups (n = 47). Prognoses were ascertained using a review of clinical charts and mailed questionnaires. Results: Only 5% of patients with SCI were able to maintain remission whereas 36% of patients without SCI were able to do so. Total duration of depressive episodes was significantly longer in the SCI-positive group than in the SCI-negative group. SCI was also associated with a higher risk of dementia. Conclusion: The results of this long-term follow-up study demonstrate that the presence of SCI is associated with a relatively poor prognosis in geriatric depression. Copyright © 2010 S. Karger AG.",,"Yamashita, H.;Fujikawa, T.;Takami, H.;Yanai, I.;Okamoto, Y.;Morinobu, S.;Yamawaki, S.",2010,August,,0,
225,The prevalence and risk factors of cerebral microbleeds in patients with Parkinson's disease,"Introduction: Cerebral microbleeds (CMBs) are frequently observed in patients with cerebrovascular disease and Alzheimer's disease. CMBs that are located in the deep or infratentorial regions and those that are present strictly in the lobar regions reflect hypertensive vasculopathy and cerebral amyloid angiopathy, respectively. The development of CMBs can be accelerated by clinical factors. Orthostatic hypotension (OH) has been reported to be associated with cerebral small vessel disease, such as white matter lesions in Parkinson's disease (PD). We investigated the prevalence, location and risk factors, including OH, for CMBs in patients with PD. Methods: We conducted a retrospective chart review of consecutive patients with PD who were admitted to the Department of Neurology, Juntendo University School of Medicine between January 2010 and July 2014. One hundred and sixty-seven patients with PD who underwent gradient echo T2*-weighted magnetic resonance imaging of the brain were included in the present study. A multivariate logistic regression analysis was performed to investigate the associations between risk factors and the presence of CMBs. Results: CMBs were detected in 29 (17.4%) patients. Among the patients with CMBs, 19 (65.5%) had deep or infratentorial CMBs and 10 (34.5%) had strictly lobar CMBs. Hypertension, OH and a history of ischemic stroke were independently associated with deep or infratentorial CMBs, whereas antiplatelet use was independently associated with strictly lobar CMBs. Conclusions: In patients with PD, deep or infratentorial CMBs were more frequent than strictly lobar CMBs, and were associated with hypertension, OH and a history of ischemic stroke.",,"Yamashiro, K.;Tanaka, R.;Hoshino, Y.;Hatano;Nishioka, K.;Hattori, N.",2015,1,,0,
226,A patient with intravascular malignant lymphomatosis presenting subacute dementia one year after sustained urinary retention and high serum LDH activity from the onset,"We report a 71-year-old man with intravascular malignant lymphomatosis who showed high serum LDH and urinary disturbance for one year before manifesting dementia. High serum LDH was found at a health check at age 70. Two months later, he had an onset of backache and urinary retention. MRI of the spinal cord was unremarkable. One year later, he showed decline of mental activities and was admitted to our hospital. He was agitated and confused. However cranial nerve palsy or limb weakness was not noted. The MRI of the brain showed T2-high signal in bilateral occipital, right temporal lobe and the left insular cortices. The abdominal CT scan showed swelling of the adrenals on both sides. Adrenal biopsy revealed diffuse large B cell lymphoma. He developed respiratory distress and he died two months after the admission. Post mortem examination revealed intravascular and extravascular proliferation of lymphoma cells in most of the internal organs including adrenals, spleen, liver and the kidneys. In the brain, the laminar necrosis was seen in the left occipital cortex and hemorrhagic infarctions were noted in the insular and temporal cortices and the medial temporal cortex. Sacral spinal cord showed necrosis of the gray matters and loss of myelinated fibers in the white matter. Intravascular proliferation of the lymphoma cells were also seen in the vessels of the brain and the spinal cord. This patient suggests the importance of survey for intravascular malignant lymphomatosis, when high serum LDH and myelopathy of lumbosacral area are seen.",lactate dehydrogenase;adrenal gland;aged;article;autopsy;B cell lymphoma;biopsy;brain;case report;clinical feature;computer assisted tomography;cranial nerve paralysis;death;dementia;disease course;human;human tissue;lactate dehydrogenase blood level;lymphoma cell;lymphomatosis;male;muscle weakness;nuclear magnetic resonance imaging;occipital cortex;respiratory distress;spinal cord;spinal cord disease;temporal lobe;urine retention,"Yamashiro, K.;Mori, H.;Suzuki, A.;Mori, K.;Hamano, Y.;Mizuno, Y.",2001,,,0,
227,A case of Ramsay Hunt syndrome with encephalitis,"A case of a seventy year old female patient with the left side Ramsay Hunt syndrome and encephalitis has been reported. Neurological impairments of the left acoustic nerve, peripheral facial palsy on the same side and slightly disturbed consciousness were observed. By cerebrospinal fluid examinations prominently increased cells and elevation of protein level were found. The highest titer against herpes zoster virus was x 1024 in serum and x 32 in liquor. Moreover, the titer against herpes simplex virus was elevated to a maximum of x 128 in serum and x 8 in liquor. CT scan revealed low density area chiefly in the frontal lobe and expanding to posterior portion of temporal lobe in the white matter of the affected side. This change was thought to be not the direct infiltration by the infection but an edematous change due to meningitis. About three months later CT scan was done but the low density area had disappeared and there were no enlargement of ventricles or sulci. According to the administration of corticosteroid hormone the clinical pictures of encephalitis improved and the patients discharged without signs of dementia. (Journal received: 21 May, 1982.)",prednisolone;case report;central nervous system;cerebrospinal fluid;computer analysis;computer assisted tomography;diagnosis;encephalitis;Herpes simplex virus;ramsay hunt syndrome;therapy;Varicella zoster virus,"Yamasaki, M.;Nomura, S.;Sera, H.",1980,,,0,
228,Evaluation of shortened protocol of graph plot method with (123)I-IMP,"The (123)I-IMP Graph Plot is a convenient method of analyzing cerebral blood flow without blood sampling. Data acquisition requires 45 minutes after the infusion of (123)I-IMP because the method is matched to the protocol of autoradiography (conventional method). However, we think that those protocols do not have to be matched because those theories are different. Therefore, we contrived a protocol for shortening that time by beginning SPECT data acquisition earlier and shortening the acquisition time compared to the conventional method. We compared count ratios of the decreased area to an area of the healthy side, quantitative values, and results of statistical analysis of the shortened protocol and the conventional method for cases of cerebral infarction and of dementia with Lewy bodies (DLB). Some count ratios of the shortened protocol were inferior to those of the conventional method, but the degrees did not affect the clinical diagnosis. In the other areas and cases also, the differences did not affect the clinical diagnosis. In addition to the results of this study, some previous reports have described that early SPECT images after infusion show the true cerebral blood flow. Therefore, we judged that this shortened protocol can be used as a clinical protocol.",,"Yamamoto, Y.;Onoguchi, M.;Wada, A.;Sarada, K.;Haramoto, M.;Komatsu, A.;Kitagaki, H.;Yamaguchi, S.",2011,2011,,0,
229,Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL,"BACKGROUND AND PURPOSE: White matter (WM) hyperintensities on MRI or leukoaraiosis is characteristic of stroke syndromes. Increased MRI signals in the anterior temporal pole are suggested to be diagnostic for cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with 90% sensitivity and 100% specificity. The structural correlates of these specific WM hyperintensities seen on T2-weighted and FLAIR sequences in the temporal pole of CADASIL are unclear. We assessed pathological changes in postmortem tissue from the temporal pole to reveal the cause of CADASIL-specific WM hyperintensities. METHODS: A combination of tinctorial and immunostaining approaches and in vitro imaging methods were used to quantify the extent of perivascular space (PVS), arteriosclerosis determined as the sclerotic index, WM myelination as the myelin index, and damage within the WM as accumulated degraded myelin basic protein in samples of the anterior temporal pole from 9 CADASIL and 8 sporadic subcortical ischemic vascular dementia cases, and 5 similarly aged (young) and 5 older controls. Luxol fast blue-stained serial sections from a CADASIL case were also used to reconstruct the temporal pole, which was then compared to the MR images. RESULTS: Luxol fast blue sections used to reconstruct the temporal pole revealed an abundance of enlarged PVS in the WM that topographically appeared as indistinct opaque regions. The mean and total areas of the PVS per WM area (%PVS) were significantly greater in CADASIL compared to the controls. The myelin index was severely reduced in CADASIL in relation to the subcortical ischemic vascular dementia and control sample that was consistent with increased immunoreactivity of degraded myelin basic protein, indicating myelin degeneration. Cerebral microvessels associated with the PVS exhibited a 4.5-fold greater number of basophilic (hyalinized) vessels and a 57% increase in the sclerotic index values in CADASIL subjects compared to young controls. A significant correlation between the quantity of hyalinized vessels and sclerotic index values was also apparent (P<0.05). CONCLUSIONS: Our findings suggest that MRI hyperintensities in the temporal pole of CADASIL patients are explained by enlarged PVS and degeneration of myelin accompanied by lack of drainage of the interstitial fluid rather than lacunar infarcts. Consistent with the lack of MR hypersignals in the temporal pole of older subcortical ischemic vascular dementia subjects, our observations imply greater progression of pathological changes in CADASIL patients.","Adult;Aged;Aging/pathology;Algorithms;CADASIL/ pathology;Capillaries/pathology;Dementia, Vascular/pathology;Female;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/pathology;Paraffin Embedding;Risk Factors;Sclerosis/pathology;Temporal Lobe/ pathology","Yamamoto, Y.;Ihara, M.;Tham, C.;Low, R. W.;Slade, J. Y.;Moss, T.;Oakley, A. E.;Polvikoski, T.;Kalaria, R. N.",2009,Jun,10.1161/strokeaha.108.528299,0,
230,"The relationship between 24-hour blood pressure readings, subcortical ischemic lesions and vascular dementia","BACKGROUND: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). METHODS: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP - nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0-0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. RESULTS: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20-9.34), advanced PVH (OR 14.42; 95% CI 5.62-36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37-115.95; reverse dipper: OR 11.95; 95% CI 1.27-112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38-11.17), high daytime (OR 2.06; 95% CI 1.03-4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13-5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03-7.05; reverse dipper: OR 3.78; 95% CI 1.38-10.34) were significantly associated with PVH. CONCLUSIONS: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.","Aged;Aged, 80 and over;*Blood Pressure;*Blood Pressure Monitoring, Ambulatory;Brain Ischemia/diagnosis/etiology/*physiopathology;Cerebral Infarction/diagnosis/etiology/physiopathology;Circadian Rhythm;Cohort Studies;Dementia, Vascular/diagnosis/etiology/*physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Risk Factors","Yamamoto, Y.;Akiguchi, I.;Oiwa, K.;Hayashi, M.;Ohara, T.;Ozasa, K.",2005,,10.1159/000084498,0,
231,Twenty-four-hour blood pressure and MRI as predictive factors for different outcomes in patients with lacunar infarct,"BACKGROUND AND PURPOSE: A long-term follow-up study was conducted in patients with lacunar infarct to assess how 24-hour blood pressure monitoring values and MRI findings, in particular lacunar infarcts and diffuse white matter lesions, can predict subsequent development of dementia and vascular events, which include cerebrovascular and cardiovascular events. METHODS: One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up. Documented events comprise the development of dementia and the occurrence of vascular events. The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis. RESULTS: Twenty-six patients developed dementia (0.17/100 patient-years). Male sex (relative risk [RR], 4.2; 95% CI, 1.2 to 14.7), cognitive impairment (RR, 3.0; 95% CI, 1.0 to 8.5), confluent DWML (moderate: RR, 7.1; 95% CI, 1.6 to 31.5; severe: RR, 35.8; 95% CI, 7.2 to 177.3), and nondipping status (RR, 7.1; 95% CI, 2.2 to 22.0) were independent predictors for dementia. Forty-six patients suffered from vascular events (3.11/100 patient-years). Diabetes mellitus (RR, 5.7; 95% CI, 2.7 to 11.9), multiple lacunae (moderate: RR, 6.4; 95% CI, 2.5 to 15.8; severe: RR, 8.5; 95% CI, 3.1 to 23.3), and high 24-hour systolic blood pressure (>145 mm Hg versus <130 mm Hg) (RR, 10.3; 95% CI, 1.3 to 81.3) were independent predictors for vascular events. CONCLUSIONS: Predictors for developing dementia and vascular events appear to differ. Male sex, confluent diffuse white matter lesions, and nondipping status were independent predictors for subsequent development of dementia, while diabetes mellitus, multiple lacunae, and high 24-hour systolic blood pressure were independent predictors for vascular events.","Aged;Blood Pressure Monitoring, Ambulatory/*methods;Brain Infarction/*diagnosis;Cardiovascular Diseases/diagnosis;Cerebrovascular Disorders/diagnosis;Dementia, Vascular/*diagnosis;Female;Follow-Up Studies;Forecasting;Humans;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Prognosis;Proportional Hazards Models","Yamamoto, Y.;Akiguchi, I.;Oiwa, K.;Hayashi, M.;Kasai, T.;Ozasa, K.",2002,Jan,,0,
232,Twenty-four-hour blood pressure changes in the course of lacunar disease,"BACKGROUND: Changes in blood pressure (BP) over time have not been considered in investigations on the relationship between BP and cerebrovascular disease (CVD). OBJECTIVE: To investigate BP changes throughout a 24-hour period in lacunar infarct patients with different outcomes. METHODS: Twelve control subjects (group 1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct patients were divided into three groups: group 2, 25 patients with a fair outcome without any cerebrovascular attack or progressive dementia (mean follow-up period: 4.4 years); group 3, 14 patients with worsening of clinical dementia rating and silent lesions, which included lacunae and diffuse white matter lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on two separate occasions. No patient was treated with antihypertensive agents during the course of the study. RESULTS: In group 2, the second measurements were significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP, 24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p < 0.05). In group 3, the second measurements were significantly lower than the first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for all). In group 4, the second measurements were significantly lower than the first for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse rate became positive for group 2 in second measurements, but was not positive for groups 3 and 4. CONCLUSIONS: BP tended to elevate over time in patients with a fair outcome. In contrast, BP tended to decrease in those who developed dementia and symptomatic infarct. Autonomic functions including sympathetic activity might play a role in changes in BP in lacunar infarct patients during the course of disease.","Aged;*Blood Pressure;Blood Pressure Monitoring, Ambulatory;Brain/pathology;Brain Infarction/*physiopathology;Dementia, Multi-Infarct;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Pulse","Yamamoto, Y.;Akiguchi, I.;Oiwa, K.;Hayashi, M.;Imai, K.",2001,,47620,0,
233,Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries,"Background It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries.Methods We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI).Results Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade < 2 versus PVH grade ≤ 1, odds ratio 6.72, P =.006; with stroke versus without stroke, odds ratio.21, P =.049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge.Conclusions PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.",,"Yamamoto, N.;Terasawa, Y.;Satomi, J.;Sakai, W.;Harada, M.;Izumi, Y.;Nagahiro, S.;Kaji, R.",2014,1,,0,
234,Increased signal in basal ganglia and white matter on magnetic resonance imaging in Creutzfeldt-Jakob disease,,Basal Ganglia/ pathology;Brain/ pathology;Creutzfeldt-Jakob Syndrome/ diagnosis;Humans;Magnetic Resonance Imaging,"Yamamoto, K.;Morimatsu, M.",1992,Jul,10.1002/ana.410320124,0,
235,Neuro-Behcet disease with demyelination and gliosis of the frontal white matter,"A rare case of neuro-Behcet disease with diffuse demyelination and gliosis of the frontal white matter is reported clinico-pathologically. The disease began with genital ulcer and recurrent oral aphthosis when the patient was 42 years of age. There was erythema, moderate fever, CSF (cerebrospinal fluid)- pleocytosis and elevated CSF-globulin. He was diagnosed as having neuro- Behcet disease and treated with prednisolone. He gradually became euphoric, disinhibited, indifferent and demented. His cranial CT showed diffuse low density areas in the bilateral frontal white matter. He became bedridden, akinetic mute and died from respiratory dysfunction 3 1/2 years after onset. The following neuropathological findings were observed: 1) Moderate demyelination and gliosis was present mainly in the frontal and parietal white matter. 2) There were many micro-spongious necrotic foci in the gray and white matters of the cerebrum, basal ganglia, thalamus, midbrain and pons, some of which were accompanied by gliosis. 3) From 1/2 to 1/3 of all micro-necrotic foci in the frontal white matter were old and accompanied by gliosis. The white matter containing numerous micro-necrotic foci had myelin pallor and gliosis. 4) There was neither micro-necrosis nor gliosis in the occipital lobe. The pathogenetic correlation of white matter lesions with primary and secondary circulatory disturbances is discussed.",methylprednisolone;prednisolone;adult;article;autopsy;Behcet disease;case report;clinical feature;computer assisted tomography;demyelination;disease course;gliosis;human;human tissue;male;neurologic disease;neuropathology;nuclear magnetic resonance imaging;oral drug administration;priority journal;white matter,"Yamamori, C.;Ishino, H.;Inagaki, T.;Seno, H.;Iijima, M.;Torii, I.;Harada, T.;Morikawa, S.",1994,,,0,
236,Diffuse white matter changes with dementia caused by dural arteriovenous fistula: Report of two cases,"We present two patients with progressive dementia who showed diffuse white matter changes on magnetic resonance imaging (MRI) associated with dural arteriovenous fistula (DAVF) involving the transverse-sigmoid sinuses. Angiography of both patients revealed that DAVF was associated with multiple occlusive changes in the dural venous sinus. The associated occlusive changes isolated the straight sinus and the DAVF from the other venous sinuses, and concentrated the drainage of the DAVF in the straight sinus. We postulate that the venous hypertension of the straight sinus resulted in the venous ischemia of the white matter, diffuse white matter changes on MRI, and progressive neurological signs including dementia. Treatment of the DAVF reversed white matter changes and neurological signs. Associated with the venous sinus occlusions, the DAVF caused dementia with diffuse white matter changes due to the venous ischemia. © 2001 Harcout Publishers Ltd.",,"Yamakami, I.;Kobayashi, E.;Yamaura, A.",2001,2001,,0,
237,Dural arteriovenous malformation presenting venous Ischemia,We report three patients with dural arteriovenous malformation (DAVM) in the posterior fossa presenting the venous ischemia and the pathophysiology and the clinical characteristics of DAVM presenting the venous ischemia are discussed. Associated with occlusive changes in the venous sinuses. DAVM in the posterior fossa develops the venous hypertension of the straight sinus and the venous ischemia of cerebral white matter and basal ganglia. The venous ischemia presents progressive symptoms consisting of dementia with or without the ensuing consciousness disturbance. Multiple parenchymal lesions and abnormally dilated and tortuous veins are the characteristic findings in MRI/CT.,adult;article;brain arteriovenous malformation;brain ischemia;brain scintiscanning;case report;clinical feature;computer assisted tomography;dementia;dura mater;female;human;intracranial hypertension;magnetic resonance angiography;male;sinus venosus,"Yamakami, I.;Hirai, S.;Ono, J.;Yamaura, A.;Karasudani, H.;Uozumi, A.",1997,,,0,
238,Changes in cerebral blood flow and oxygen metabolism related to magnetic resonance imaging white matter hyperintensities in Alzheimer's disease,"We studied changes in cerebral perfusion and oxygen metabolism to elucidate the pathophysiological nature and clinical significance of white matter hyperintensities in Alzheimer's disease (AD). METHODS: Sixteen AD patients (age 71.6 +/- 3.1 yr) whose T2-weighted MR images showed white matter hyperintensities, and 16 age-matched AD patients (age 71.0 +/- 4.3 yr) without white matter hyperintensities were compared. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured by using (15)O steady-state method and PET. RESULTS: There was no significant difference in cognitive impairment between the two groups. Compared to the patients without white matter hyperintensities, those with them had significantly low CBF values and significantly high OEF values in all cortical and white matter regions. However, there were no significant differences in CMRO2 values between the two groups. Severity of white matter hyperintensities correlated with the mean cortical and mean white matter OEF. CONCLUSION: In AD patients, white matter hyperintensities on T2-weighted MR images represent ischemic changes in which oxygen metabolism and function are fairly compensated. These changes are not disease-specific but are age-associated coincidences, as in normal aging with or without vascular risk factors.","Aged;Alzheimer Disease/diagnosis/metabolism/ physiopathology/radionuclide imaging;Brain/metabolism/ pathology/radionuclide imaging;Cerebrovascular Circulation;Female;Humans;Magnetic Resonance Imaging;Male;Oxygen/ metabolism;Tomography, Emission-Computed","Yamaji, S.;Ishii, K.;Sasaki, M.;Imamura, T.;Kitagaki, H.;Sakamoto, S.;Mori, E.",1997,Sep,,0,
239,Immunohistochemistry and in situ hybridization of T-cell acute lymphoblastic leukemia-associated antigen 1 in human brain tissues,"One of the proteins belonging to the transmembrane 4 superfamily, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA1), behaves like a potential tumor-associated antigen. Furthermore, its mRNA is expressed in normal brain. We examined here the histochemical localization of the protein and its mRNA in human brain tissues. Both nonneurological and Alzheimer disease (AD) brains showed astroglial staining for the TALLA1 molecule. In AD brain tissues, globular dystrophic neurites were positively stained. In damaged white matter showing leukoaraiosis by CT scan there was varicose axonal staining with the anti-TALLA1 antibody. In situ hybridization histochemistry using a RNA probe demonstrated neuronal expression of the mRNA. These results suggest that TALLA1, like amyloid precursor protein or chromogranin A, is produced in neurons and transported by axonal flow.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/pathology;Animals;Antigens, Neoplasm/biosynthesis/*metabolism;Axons/pathology;Blotting, Western;Brain/*metabolism;Female;Humans;Immunohistochemistry;In Situ Hybridization;Leukemia-Lymphoma, Adult T-Cell/*immunology;Male;Membrane Glycoproteins/biosynthesis/*metabolism;Plaque, Amyloid/metabolism/pathology;RNA Probes;RNA, Messenger/biosynthesis/genetics;Rats","Yamada, T.;Tsujioka, Y.;Takahashi, M.;Tsuboi, Y.;Taguchi, J.;Yoshie, O.",1999,Mar-Apr,17102,0,
240,A small cerebral infarction in the basal ganglia causing progressive psychosis followed by dementia,"A 70-year-old woman was admitted to our hospital because of an obsessive state with irritability and visual hallucination. She had suffered a mild head injury two weeks ago, but computed tomography (CT) scan of the brain showed no traumatic lesions. And acute responsive psychosis was suspected, but a low score of 8 points (full score of 30 points) on Hasegawa dementia scale (HDS -R) suggested occult cerebral lesions. Magnetic resonance imaging (MRI) revealed a new small ischemic change from the posterior limb of the left internal capsule to the tail of the left caudate nucleus by diffusion-weighted imaging, in addition to multiple old lacunar infarctions in bilateral basal ganglias in T 2-weighted imaging and fluid attenuated inversion recovery. After improvement of her mental irritability, the patient still displayed dementia with severe recent memory disturbance. Psychological analysis demonstrated vascular dementia, and her HDS -R score was only 9 points when she was discharged our hospital 6 weeks after admission. Therefore, the authors concluded that her psychosis-like reactions and severe dementia had been caused by the small infarction. We emphasize that a new small infarction may cause dementia as ""multi-infarct dementia"" in patients with multiple old lacunar infarctions in bilateral basal ganglias, even though the new ischemic lesions may not be anatomically associated with the mental symptoms.",,"Yamada, S. M.;Nakane, M.;Aoki, M.;Nakayama, H.;Cho, Y.",2005,Dec,,0,
241,Severe underweight and cerebral microbleeds,"Severely low and/or high body mass index (BMI) has been associated with intracerebral hemorrhage (ICH) risk in several large cohorts. The aim of this study is to assess the relationship between BMI and the presence of cerebral microbleeds. The presence and number of microbleeds were assessed on three-dimensional T2-weighted gradient-recalled-echo sequence on magnetic resonance imaging (MRI). The inclusion criteria were participants aged >40 years old without aneurysmal subarachnoid hemorrhage and any type of cerebral vascular malformations. BMI was categorized into severe underweight (<17.0 kg/m(2)), mild underweight (17.0-18.4 kg/m(2)), normal range (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)), and obese (>/= 30.0 kg/m(2)). Multivariate analyses were adjusted for age, sex, hypertension, smoking, alcohol, stroke subtype, severity of periventricular hyperintensities and deep white matter hyperintensities, and dementia. Additionally, we conducted stratification analyses by age, ICH, smoking habit, or history of any kind of cancer, respectively. A total of 384 participants (232 males, 152 females; mean age 67.5 years) met our inclusion criteria. Overall mean BMI was 22.8 +/- 3.6 kg/m(2). On multivariate analyses, severe underweight carried a significantly higher risk for cerebral microbleeds (3.48, 1.06-11.4) compared with normal range BMI, even after stratification in the subgroup aged >/= 60 years (7.23, 1.57-33.2), nonsmokers (4.75, 1.10-20.5), noncancer subgroup (5.66, 1.31-24.5), and non-ICH subgroup (3.81, 1.14-12.7). We found that severe underweight was an independent significant risk factor for presence of cerebral microbleeds, even after effect of aging, smoking, or preexisting illness was eliminated.","Adult;Aged;Aged, 80 and over;Body Mass Index;Cerebral Hemorrhage/ diagnosis/ epidemiology;Female;Humans;Male;Microcirculation/physiology;Microvessels/ pathology;Middle Aged;Prospective Studies;Severity of Illness Index;Thinness/ diagnosis/ epidemiology","Yamada, S.;Satow, T.;Fukuda, A.;Ito, M.;Saiki, M.",2012,Dec,10.1007/s00415-012-6574-7,0,
242,Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age,"Background: Taking an advantage of the high sensitivity of 3D T2*-weighted gradient-recalled-echo (GRE) imaging to cerebral microbleeds, we investigated the relationship between cerebral microbleeds and leukoaraiosis. Methods: Participants aged 40years or more have been evaluated for the presence of cerebral microbleeds using 3D T2*-GRE sequence since 2006. The severity of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on fluid attenuated inversion recovery images was assessed using Fazekas rating scales. Multivariate logistic regression analyses were conducted after adjustment for stroke subtype, age, PVH, DWMH, hypertension, dementia, and use of platelet aggregation inhibitors. Additionally, we examined the association between cerebral microbleeds and other covariates using a Pearson's correlation analysis. Results: Amongst 389 patients, 67 patients had a single microbleed and 93 had multiple microbleeds. The prevalence of microbleeds was 83% amongst 53 patients with intracerebral hemorrhage (ICH), 49% amongst 173 with infarction, and 20% amongst 163 without any type of stroke. In the multivariate analyses, the odds ratio (95% CIs) of microbleed detection was 10.1, (4.12-24.8) for ICH, 2.33 (1.12-4.85) for atherosclerotic infarction, 1.66 (1.10-2.48) for PVH, and 1.49 (1.02-2.19) for DWMH. In the Pearson's correlation analysis, cerebral microbleeds were closely related to PVH (Pearson's correlation coefficient; 0.48) and DWMH (0.37), compared with age (0.16). Conclusions: High-grade PVH, high-grade DWMH, ICH, and atherosclerotic infarction were significantly independent predictors for cerebral microbleeds. In addition, we found that the grades of PVH and DWMH have a closer association with the number of cerebral microbleeds than age. Click to view the accompanying paper in this issue. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.",,"Yamada, S.;Saiki, M.;Satow, T.;Fukuda, A.;Ito, M.;Minami, S.;Miyamoto, S.",2012,January,,0,
243,Panencephalopathic type of Creutzfeldt-Jakob disease associated with cadaveric dura mater graft,"A 52 year old man with Creutzfeldt-Jakob disease who received a cadaveric dura mater graft 99 months before the onset is reported. The prion protein gene was homozygous for methionine at the polymorphic codon 129. Neuropathological examination disclosed a panencephalopathic type of Creutzfeldt-Jakob disease which was characterised by severe involvement of the cerebral white matter and cerebellum, as well as of the cerebral cortical and deep grey matter. Thus the panencephalopathic type of Creutzfeldt-Jakob disease may occur in association with cadaveric dura mater grafts.",methionine;prion protein;adult;brain cortex;cadaver donor;case report;cerebellum;clinical feature;Creutzfeldt Jakob disease;dura mater;genetic polymorphism;gray matter;homozygosity;human;human tissue;male;medical literature;meningioma;neuropathology;nuclear magnetic resonance imaging;panencephalitis;priority journal;short survey;tissue graft;white matter,"Yamada, M.;Itoh, Y.;Suematsu, N.;Matsushita, M.;Otomo, E.",1997,,,0,
244,Detection of early neuronal damage in CADASIL patients by q-space MR imaging,"INTRODUCTION: q-Space imaging is a novel magnetic resonance (MR) technique that enables the assessment of ultrastructural changes of white matter. We hypothesized that this technique would facilitate the assessment of the progressive nature of neuronal damage seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: This study was approved by the institutional review board. Seven consecutive adult patients (five men and two women) with the CADASIL gene mutation were studied. Two patients were preclinical cases without overt episodes of stroke. The control group consisted of five normal volunteers. All MR examinations were performed using a 1.5-T whole-body imager. q-Space imaging was performed using a single-shot, echo-planar imaging technique and Delta/delta = 142/17 ms. Gradient magnitudes were increased in nine steps to reach a maximal b value of 10,000 s/mm(2). Total acquisition time of q-space imaging was 25 min. The ADC maps calculated from the b = 1,000 images were used for comparisons. RESULTS: Both q-space imaging and ADC maps depicted progressive neuronal damage. Early neuronal damage was especially well depicted using q-space imaging, with preferential involvement of the frontal lobes and central gray matters. Later progression was better depicted by b = 1,000 ADC maps at the temporal lobes. Visual assessment of images revealed a trend for occipital lobe sparing, especially on q-space imaging. CONCLUSION: q-Space imaging demonstrated early neuronal damage in a characteristic distribution. Since this method appears to be sensitive to early neuronal damage, it could conceivably aid in monitoring patients in the preclinical stage and may help in assessing the effects of future medical interventions.","Adult;Aged;CADASIL/ pathology;Early Diagnosis;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Reproducibility of Results;Sensitivity and Specificity","Yamada, K.;Sakai, K.;Akazawa, K.;Sugimoto, N.;Nakagawa, M.;Mizuno, T.",2013,Feb,10.1007/s00234-012-1105-x,0,
245,Report of a patient with CADASIL having a novel missense mutation of the Notch 3 gene - Association with alopecia and lumbar herniated disk,"We report a 52-year-old man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting dementia, alopecia and lumbar herniated disk. He had an episode of stroke and migraine-like headache lasting for 5 minutes. A lot of members had cerebral infarction in this family. Brain magnetic resonance imaging demonstrated, on T2-weighted images, numerous hyperintense lesions suggestive of small infarcts in the basal ganglia and diffuse hyperintense lesions in the cerebral white matter. The clinical symptoms, the family history and the MRI findings suggested the diagnosis of CADASIL. However, the patient also showed alopecia and lumbar herniated disk, both are characteristic features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). The DNA analysis of the Notch 3 gene identified a novel missense mutation Cys174Phe in this patient. Our case report indicated the importance of the DNA analysis for the diagnosis of CADASIL.",,"Yamada, H.;Yasuda, T.;Kotorii, S.;Takahashi, K.;Tabira, T.;Sunada, Y.",2001,2001,,0,
246,Topographical and quantitative assessment of white matter injury following a focal ischaemic lesion in the rat brain,"Axonal injury following cerebral ischaemia has attracted less attention than damage in grey matter. However, it is becoming increasingly recognised that axons are highly vulnerable to focal ischaemia [D. Dewar, D.A. Dawson, Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat, Acta. Neuropathol., 93 (1997) 71-77] [2]; [L. Pantoni, J.H. Garcia, J.A. Gutierrez, Cerebral white matter is highly vulnerable to ischemia, Stroke, 27 (1996) 1641-1647] [10]; [P. S. Yam, T. Takasago, D. Dewar, D.I. Graham, J. McCulloch, Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion, Brain Res., 760 (1997) 150-157] [15]. Since white matter does not contain neuronal cell bodies or synapses it is likely that the mechanisms of injury and strategies for its protection are different from those in grey matter. In order that the effect of therapeutic intervention on the protection of axons can be assessed, a method by which axonal injury can be mapped and quantified is required. For this purpose, we investigated immunocytochemical methods using amyloid precursor protein (APP) following permanent middle cerebral artery occlusion in the rat. APP is transported by fast anterograde axonal transport [E.H. Koo, S.S. Sisodia, D.R. Archer, L.J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C.L. Masters, D.L. Price, Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 1561-1565] [7] and has been shown to accumulate following a variety of insults to axons, indicative of dysfunction of axonal transport [R.N. Kalaria, S.U. Bhatti, E.A. Palatinsky, D.H. Pennington, E.R. Shelton, H.W. Chan, G. Perry, W.D. Lust, Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain, Neuroreport, 4 (1993) 211-214] [4]; [T. Kawarabayashi, M. Shoji, Y. Harigaya, H. Yamaguchi, S. Hirai, Expression of APP in the early stage of brain damage, Brain Res., 563 (1991) 334-338] [5]; [N. Otsuka, M. Tomonaga, K. Ikeda, Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury, Brain Res., 568 (1991) 335-338] [9]; [K. Shigematsu, P. L. McGeer, Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine, Am. J. Pathol., 140 (1992) 787-794] [12]. We have been able to map the topographical relationship between APP accumulation and region of infarction using immunocytochemistry and image analysis techniques. Additionally, using a semi-quantitative scoring system, we have demonstrated that there is a relationship between the amount of APP accumulation and the volume of infarction following middle cerebral artery occlusion. These methods will be useful in the future for the assessment of therapeutic interventions on the protection of axons following ischaemic injury.","Amyloid beta-Protein Precursor/analysis;Animals;Axons/ pathology;Brain Mapping;Cerebral Infarction/ pathology;Evaluation Studies as Topic;Immunohistochemistry;Ischemic Attack, Transient/ pathology;Male;Rats;Rats, Inbred F344","Yam, P. S.;Patterson, J.;Graham, D. I.;Takasago, T.;Dewar, D.;McCulloch, J.",1998,Jun,,0,
247,"The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis","BACKGROUND AND PURPOSE: Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS. METHODS: In total, 146 patients with MS (mean age 49.0 +/- 10.9 years, disease duration 21.2 +/- 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0-7.5), 103 relapsing-remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age- and gender-matched control subjects. The olfactory bulb was semi-automatically segmented on high-resolution three-dimensional T1-weighted MRI. RESULTS: Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 +/- 40.1 vs. 209.2 +/- 59.3 mul; P = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = -0.38, P < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing-remitting MS. CONCLUSION: Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.",,"Yaldizli, O.;Penner, I. K.;Yonekawa, T.;Naegelin, Y.;Kuhle, J.;Pardini, M.;Chard, D. T.;Stippich, C.;Kira, J. I.;Bendfeldt, K.;Amann, M.;Radue, E. W.;Kappos, L.;Sprenger, T.",2016,Mar,10.1111/ene.12891,0,
248,Brain microbleeds and global cognitive function in adults without neurological disorder,"BACKGROUND AND PURPOSE: Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. METHODS: A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores <27 or >1.5 SDs below the age-related mean were regarded as subnormal. RESULTS: MBs were found in 35 subjects (6.8%). MMSE score <27 was found in 25 subjects (4.8%), with MMSE score >1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score <27. Logistic regression analysis revealed a significant relationship between presence (OR, 3.93; 95% CI, 1.44 to 10.74) and number (OR, 1.26; 95% CI, 1.01 to 1.59) of MBs and MMSE score >1.5 SDs below the age-related mean. Among MMSE subscores, ""attention and calculation"" was significantly lower in MB-positive subjects (P=0.017). CONCLUSIONS: MBs appear to be primarily associated with global cognitive dysfunction.","Adult;Aged;Aged, 80 and over;Cerebral Hemorrhage/*complications/epidemiology/psychology;Cognition Disorders/epidemiology/*etiology;Comorbidity;Dementia, Vascular/epidemiology/*etiology/psychology;Diabetes Mellitus/epidemiology;Female;Humans;Hyperlipidemias/epidemiology;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Mass Screening;Middle Aged;Neuropsychological Tests;Prospective Studies;Smoking/epidemiology","Yakushiji, Y.;Nishiyama, M.;Yakushiji, S.;Hirotsu, T.;Uchino, A.;Nakajima, J.;Eriguchi, M.;Nanri, Y.;Hara, M.;Horikawa, E.;Kuroda, Y.",2008,Dec,10.1161/strokeaha.108.516112,0,
249,[Cerebral microbleeds: clinical features and management],"Cerebral microbleeds (CMBs) on gradient-echo T(2) weighted MRI, which are characterized histologically by the presence of hemosiderin around small vessels, are now accepted as a manifestation of cerebral small vessel disease (SVD) pathologies, including hypertensive small vessel disease and cerebral amyloid angiopathy (CAA). CMBs are often detected in patients with stroke, Alzheimer's disease, and mild cognitive impairment. The pathological differences in MBs according to distribution is now well known, with MBs in deep regions considered to be associated with hypertensive arteriopathy, whereas strictly lobar MBs share risk factors with CAA. Evidence suggests that CMBs should not be considered to be clinically ""silent"". When CMBs are detected in healthy adults, physicians should recognize that subclinical SVD might have begun in their brain. Chronic hypertension can affect HA-related CMBs, as well as CAA-related CMBs. Furthermore, both types of CMBs are risk factor for intracranial hemorrhage under the antithrombotic drug use. Thus, CMBs should be considered as ""warning sign"" for inappropriate blood pressure control and antithrombotic drug use. It seems clear that CMBs should be an important component of future studies to investigate how SVD influence neurodegeneration via neurovascular units in elderly populations.",Alzheimer Disease/complications;*Cerebral Hemorrhage/etiology;Cerebral Small Vessel Diseases/etiology;Humans,"Yakushiji, Y.;Hara, H.",2012,,,0,
250,"Cerebral Microbleeds: Detection, Associations and Clinical Implications","Vigorous investigations for cerebral microbleeds (CMBs) have been made since the late 1990s. CMBs on paramagnetic-sensitive magnetic resonance sequences correspond pathologically to clusters of hemosiderin-laden macrophages and have emerged as an important new imaging marker of cerebral small vessel disease, including intracerebral hemorrhage (ICH). The prevalence of CMBs varies according to the specific disease settings (stroke subtypes and dementing disorders) and is highest (60%) in ICH patients. The associations of CMBs with aging, hypertension and apolipoprotein E genotype are consistent with the two major underlying pathogeneses of CMBs: hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). The distributional patterns of CMBs might help us to understand the predominant small vessel disease pathogenesis in the brain; the strictly lobar type of CMBs often reflects the presence of advanced CAA, while the other types of CMBs, such as 'deep or infratentorial CMBs', including the mixed type, are strongly associated with hypertension. CMBs might be associated with cognitive function (especially executive function), gait performance, and cerebrovascular events (spontaneous, antithrombotic drug-related or post-thrombolysis ICH). In the field of CAA, an understanding of CAA-related CMBs might help to guide decision making with regard to new therapeutic approaches, including the use of monoclonal antibodies against vascular amyloid. These concepts of CMBs might allow us to advance research on ICH as well as for dementia.",,"Yakushiji, Y.",2015,,10.1159/000437115,0,
251,Effects of carotid endarterectomy on the dynamics of cognitive impairments in patients with atherosclerotic stenosis of the carotid arteries,"The clinical and neurochemical characteristics of non-dementia cognitive disorders were studied in 102 patients with atherosclerotic carotid sclerosis, with assessment of their dynamics after carotid endarterectomy (CEAE). Mild cognitive disorders were seen in 37 patients (36.3%) and moderate cognitive disorders in 36 patients (35.3%). Moderate cognitive impairments were significantly more common in patients with symptoms of carotid stenosis, dominated by structural changes in the brain on neuroimaging (leukoaraiosis and infarcts); unstable atherosclerotic plaques, with a predominance of the hypodense component, were also more frequent. This suggests that cognitive dysfunction in patients with atherosclerotic carotid stenosis results not only from decreased perfusion, but also from arterio-arterial microembolism. CEAE was found to have favorable effects on cognitive functions. Positive changes were marked in patients with asymptomatic carotid stenosis. However, CEAE could also have adverse influences on cognitive functions in patients with moderate cognitive disorders of dysmnestic type and symptoms of carotid stenosis. © 2012 Springer Science+Business Media, Inc.",adult;article;atherosclerotic plaque;brain infarction;brain perfusion;carotid artery obstruction;carotid atherosclerosis;carotid endarterectomy;cognitive defect;deterioration;disease severity;female;human;internal carotid artery occlusion;leukoaraiosis;major clinical study;male;memory disorder;microembolism;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging,"Yakhno, N. N.;Fedorova, T. S.;Damulin, I. V.;Shcherbyuk, A. N.;Vinogradov, O. A.;Lavrentiev, A. V.",2012,,,0,
252,MRI of non-neoplastic cranial complications of malignant disorders,"Purpose: To depict the well-known and atypical magnetic resonance imaging (MRI) findings of neo-neoplastic central nervous system (CNS) complications of extra-CN5 tumors and portray additional information from advanced techniques, such as diffusion and perfusion MRI. Materials and Methods: MRI scans of 92 patients were retrospectively evaluated based on the non-neoplastic effects induced by treatment or the remote effects of the tumor itself. Patients with brain metastases and/or patients who had whole brain radiation therapy were excluded so as not to take the primary radiation effects into consideration. Results: Sixteen patients (9 females and 7 males; age range, 11-68 years; median age, 45 years) had positive findings other than brain metastases. Six patients had posterior reversible encephalopathies, 3 patients had chemotherapy toxicity to the white matter, and 2 patients had acute strokes involving the posterior fossa and bilateral anterior circulation territory. Three patients had bilateral radionecrosis of the temporal lobe due to radiotherapy given for the vicinal tumor (nasopharyngeal carcinoma). One patient had encephalitis in the bitemporal region and one patient had cerebellar degeneration, each of whom had a paraneoplastic syndrome. Conclusion: One of the major and noteworthy complications of malignancies directly affecting survival is brain metastasis, but non-neoplastic complications are infrequently encountered and are thus underestimated, either due to the absence of a true diagnosis or the lack of information pertaining to the clinical outcome. It is important for the radiologist to recognize these effects so as to help the clinician develop an optimal treatment strategy and avoid irreversible complications. © Turkish Society of Radiology 2008.",,"Yaǧmurlu, B.;Akyürek, S.;Fitoz, S.;Demirkazik, A.",2008,June,,0,
253,Increasing microbleeds in CADASIL,,adult;brain hemorrhage;CADASIL;cardiovascular risk;case report;diabetes mellitus;gene;genetic screening;human;hypertension;male;mutational analysis;Notch3 gene;note;nuclear magnetic resonance imaging;pathogenesis;priority journal;temporal lobe;white matter,"Yagi, T.;Konoeda, F.;Mizuta, I.;Mizuno, T.;Suzuki, N.",2013,,,0,
254,Imaging parameters and recurrent cerebrovascular events in patients with minor stroke or transient ischemic attack,"Importance: Neurological worsening and recurrent stroke contribute substantially to morbidity associated with transient ischemic attacks and strokes (TIA-S). Objective: To determine predictors of early recurrent cerebrovascular events (RCVEs) among patients with TIA-S and National Institutes of Health Stroke Scale scores of 0 to 3. Design, Setting, and Participants: A retrospective cohort studywas conducted at 2 tertiary care centers (Columbia University Medical Center, New York, New York, and Tulane University Medical Center, New Orleans, Louisiana) between January 1, 2010, and December 31, 2014. All patients with neurologist-diagnosed TIA-S with a National Institutes of Health Stroke Scale score of 0 to 3 who presented to the emergency department were included. Main Outcomes and Measures: The primary outcome (adjudicated by 3 vascular neurologists) was RCVE: neurological deterioration in the absence of a medical explanation or recurrent TIA-S during hospitalization. Results: Of the 1258 total patients, 1187 had no RCVEs and 71 had RCVEs; of this group, 750 patients (63.2%) and 39 patients (54.9%), respectively, were aged 60 years or older. There were 505 patients with TIA-S at Columbia University; 31 (6.1%) had RCVEs (15 patients had neurological deterioration only, 11 had recurrent TIA-S only, and 5 had both). The validation cohort at Tulane University consisted of 753 patients; 40 (5.3%) had RCVEs (24 patients had neurological deterioration only and 16 had both). Predictors of RCVE in multivariate models in both cohorts were infarct on neuroimaging (computed tomographic scan or diffusion-weighted imaging sequences onmagnetic resonance imaging) (Columbia University: not applicable and Tulane University: odds ratio, 1.75; 95%CI, 0.82-3.74; P = .15) and large-vessel disease etiology (Columbia University: odds ratio, 6.69; 95%CI, 3.10-14.50 and Tulane University: odds ratio, 8.13; 95%CI, 3.86-17.12; P < .001). There was an increase in the percentage of patients with RCVEs when both predictors were present. When neither predictor was present, the rate of RCVE was extremely low (up to 2%). Patients with RCVEs were less likely to be discharged home in both cohorts. Conclusions and Relevance: In patients with minor stroke, vessel imaging and perhaps neuroimaging parameters, but not clinical scores, were associated with RCVEs in 2 independent data sets. Prospective studies are needed to validate these predictors.",adult;age;aged;article;brain infarction;cerebrovascular accident;cohort analysis;computer assisted tomography;controlled study;diastolic blood pressure;diffusion weighted imaging;female;hospital discharge;hospitalization;human;large vessel disease stroke;major clinical study;male;mental deterioration;National Institutes of Health Stroke Scale;neuroimaging;priority journal;prospective study;Rankin scale;retrospective study;systolic blood pressure;tertiary care center;transient ischemic attack;United States,"Yaghi, S.;Rostanski, S. K.;Boehme, A. K.;Martin-Schild, S.;Samai, A.;Silver, B.;Blum, C. A.;Jayaraman, M. V.;Siket, M. S.;Khan, M.;Furie, K. L.;Elkind, M. S. V.;Marshall, R. S.;Willey, J. Z.",2016,,,0,
255,Sleep Duration and White Matter Quality in Middle-Aged Adults,"STUDY OBJECTIVES: Sleep duration has been associated with risk of dementia and stroke, but few studies have investigated the relationship between sleep duration and brain MRI measures, particularly in middle age. METHODS: In a prospective cohort of 613 black and white adults (mean age = 45.4 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, participants reported typical sleep duration, dichotomized into moderate sleep duration (> 6 to </= 8 h) and short sleep duration (</= 6 h) at baseline (2005-2006). Five years later, we obtained brain MRI markers of white matter including fractional anisotropy, mean diffusivity, and white matter hyperintensities. RESULTS: Compared to moderate sleepers, short sleepers had an elevated ratio of white matter hyperintensities to normal tissue in the parietal region (OR = 2.31, 95% CI: 1.47, 3.61) adjusted for age, race/sex, education, hypertension, stroke/TIA, depression, smoking status, and physical activity. White matter diffusivity was also higher, approximately a 0.2 standard deviation difference, in frontal, parietal, and temporal white matter regions, among those reporting shorter sleep duration in (P < 0.05 for all). CONCLUSIONS: Short sleep duration was associated with worse markers of white matter integrity in midlife. These mid-life differences in white matter may underlie the link between poor sleep and risk of dementia and stroke.",midlife;sleep duration;white matter hyperintensities;white matter integrity,"Yaffe, K.;Nasrallah, I.;Hoang, T. D.;Lauderdale, D. S.;Knutson, K. L.;Carnethon, M. R.;Launer, L. J.;Lewis, C. E.;Sidney, S.",2016,,10.5665/sleep.6104,0,
256,The first Indian-origin family with genetically proven cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"We report the first family of Indian origin known to be affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Seventeen members of the family spanning 3 generations had neurologic syndromes compatible with CADASIL, of whom 5 were genetically confirmed carriers of the Notch3 gene R141C mutation in exon 4 (421(C-->T) and 141(Cys-->Arg)). Our report highlights that CADASIL not only occurs sporadically in South Asians, but also may account for stroke in South Asians with a strong family history. Furthermore, the similarity of clinical presentations described here to those typical for Caucasian case series suggests that the CADASIL phenotype is preserved across racial groups.","Adolescent;Adult;Aged;Aged, 80 and over;Asian Continental Ancestry Group/*genetics;CADASIL/diagnosis/ethnology/*genetics/physiopathology;DNA Mutational Analysis;Exons;Female;Genetic Predisposition to Disease;Humans;India/ethnology;Magnetic Resonance Imaging;Male;Middle Aged;*Mutation, Missense;Nervous System/physiopathology;Pedigree;Phenotype;Predictive Value of Tests;Receptors, Notch/*genetics;Wills;Young Adult","Yadav, S.;Bentley, P.;Srivastava, P.;Prasad, K.;Sharma, P.",2013,Jan,10.1016/j.jstrokecerebrovasdis.2011.05.023,0,
257,Association of rs2075575 and rs9951307 polymorphisms of aqp-4 gene with leukoaraiosis,"Leukoaraiosis (LA) is associated with structural and functional vascular changes that correlate with motor and gait disturbances, depressive symptoms, urinary disturbances, and dementia. The blood-brain barrier (BBB) plays a key role in development of lacunar stroke, leukoaraiosis, and other feature of cerebral small-vessel disease, and there are numerous studies examining changes in the BBB with normal aging and in dementia and LA. Aquaporin-4 (AQP-4), the primary water channel protein in the central nervous system, is involved in BBB development, function, and integrity, and its dysfunction induces several neurologic diseases. The aim of our study was to evaluate whether genetic variations in AQP-4 gene are associated with the development of LA. Methods: DNA was amplified and the single-nucleotide polymorphisms in AQP-4 gene were investigated by melting curve analysis using real-time polymerase chain reaction. Results: The frequency of both T allele and CT/TT genotypes of rs2075575 was significantly higher in LA group than in control group (C versus T, P =.0145; CC versus CT/TT, P =.038). However, no significant difference was observed between LA group and control group in rs9951307. Interestingly, the rs9951307 AG + GG genotype may confer a synergistic effect in odds ratio (OR) values when combined with the rs2075575 CT + TT genotypes (OR = 1.65 → 2.51). The C-A haplotype was significantly different between LA group and the control group (P =.005). By stratified analysis, rs2075575 and rs9951307 polymorphisms were statistically significant in the subjects with hypertension and hemoglobin A1c (P <.05), whereas the rs2075575 polymorphism was associated with high serum cholesterol (P <.05) and the rs9951307 polymorphism was associated with low serum homocysteine (P <.05). Conclusions: Our results indicate that AQP-4 genetic variations and haplotypes might contribute to the risk factors for LA. © 2014 by National Stroke Association.",aquaporin 4;cholesterol;creatinine;hemoglobin A1c;homocysteine;adult;age;aged;amino acid blood level;aquaporin 4 gene;article;cholesterol blood level;controlled study;diastolic blood pressure;gene;gene frequency;genetic association;genetic risk;genetic variability;genotype;haplotype;human;hypertension;leukoaraiosis;middle aged;priority journal;real time polymerase chain reaction;single nucleotide polymorphism;systolic blood pressure,"Yadav, B. K.;Oh, S. Y.;Kim, N. K.;Shin, B. S.",2014,,,0,
258,Fragile X dementia parkinsonism syndrome (FXDPS),"BACKGROUND/OBJECTIVE: The fragile X-associated tremor/ataxia syndrome is characterized by intention tremor and ataxia in people who are premutation carriers of the Fragile X gene. Patients with this disorder might also demonstrate signs of dementia with parkinsonian features. We report a patient with dementia and parkinsonian signs who did not demonstrate an intention tremor or gait ataxia. METHODS: A 58-year-old woman who had 2 sons with fragile X retardation syndrome and was a carrier, developed progressive dementia, including impaired memory, executive dysfunction, nonfluent speech, and parkinsonian signs, but had no action-intention tremor and no gait ataxia. Magnetic resonance imaging revealed extensive abnormalities of the white matter. RESULTS: On post-mortem examination, 7 years after this evaluation, she demonstrated extensive subcortical white matter pallor (spongiosis) and widespread ubiquitin-positive intranuclear inclusions in both neurons and in protoplasmic astrocytes characteristic of fragile X-associated tremor/ataxia syndrome, but no spongiosis in the cerebellar peduncles a defining feature of this tremor/ataxia syndrome. CONCLUSIONS: Patients who present with dementia and signs of Parkinson syndrome, even in the absence of ataxia or intention tremor should be evaluated for this fragile X dementia parkinsonism syndrome. Copyright © 2010 by Lippincott Williams & Wilkins.",,"Yachnis, A. T.;Roth, H. L.;Heilman, K. M.",2010,March,,0,
259,Tissue Probability Map Constrained 4-D Clustering Algorithm for Increased Accuracy and Robustness in Serial MR Brain Image Segmentation,"The traditional fuzzy clustering algorithm and its extensions have been successfully applied in medical image segmentation. However, because of the variability of tissues and anatomical structures, the clustering results might be biased by the tissue population and intensity differences. For example, clustering-based algorithms tend to over-segment white matter tissues of MR brain images. To solve this problem, we introduce a tissue probability map constrained clustering algorithm and apply it to serial MR brain image segmentation, i.e., a series of 3-D MR brain images of the same subject at different time points. Using the new serial image segmentation algorithm in the framework of the CLASSIC framework, which iteratively segments the images and estimates the longitudinal deformations, we improved both accuracy and robustness for serial image computing, and at the mean time produced longitudinally consistent segmentation and stable measures. In the algorithm, the tissue probability maps consist of both the population-based and subject-specific segmentation priors. Experimental study using both simulated longitudinal MR brain data and the Alzheimer's Disease Neuroimaging Initiative (ADNI) data confirmed that using both priors more accurate and robust segmentation results can be obtained. The proposed algorithm can be applied in longitudinal follow up studies of MR brain imaging with subtle morphological changes for neurological disorders.",,"Xue, Z.;Shen, D.;Li, H.;Wong, S.",2011,,10.1504/ijmei.2011.042874,0,
260,MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease,"Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T(1) WI, FSE T(2)WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T(1) WI or in FSE T(2) WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely.",,"Xue, Y. G.;Qi, J.;Xia, S.",2007,July,,0,
261,Novel mutation in the ABCA1 gene identified in a Chinese patient with dementia and atherothrombotic cerebral infarction,"Background: To date, 81 mutations of ATP-binding cassette transporter 1 (ABCA1) have been reported. However, no ABCA1 mutation has been reported in the Chinese population. Methods: We used direct sequencing to screen for ABCA1 mutations in 72 patients with both atherosclerotic cerebral infarction (ACI) and plasma high-density lipoprotein cholesterol (HDL-C) < 0.8 mmol/l. The functionality of the mutation was verified using 200 unrelated controls and 76 patients with ACI and normal HDL-C by PCR-RFLP analysis. Results: One patient with dementia prior to ACI was found to carry the heterozygous Y2206D mutation, which has not been reported previously. The patient had a medical history of atherosclerosis in the coronary and carotid arteries going back 40 years and splenohepatomegalia for 13 years, with a low plasma HDL-C level (0.66 mmol/l) and apolipoprotein A1 level (0.61 mmol/l). During the past decade, he had developed symptoms of dementia. Sixteen months prior to the study, he was admitted to hospital for an ACI. Conclusion: The results suggest that this patient is most likely a patient with familial hypoalphalipoproteinemia and that the Y2206D mutation may be associated with not only a lower level of HDL-C, but also with dementia. Copyright © 2008 S. Karger AG.",apolipoprotein A1;high density lipoprotein cholesterol;ABC transporter A1 gene;adult;aged;article;blood level;brain atherosclerosis;brain infarction;Chinese;control group;controlled study;dementia;disease duration;familial hypoalphalipoproteinemia;gene;gene mutation;gene sequence;genetic identification;hepatosplenomegaly;heterozygosity;hospital admission;human;major clinical study;nuclear magnetic resonance imaging;nucleotide sequence;polymerase chain reaction;priority journal;restriction fragment length polymorphism;screening,"Xue, X. H.;Wang, N.;Lin, Y.;Zhao, G. X.;Fang, L.;Murong, S.;Wu, Z. Y.",2008,,,0,
262,Initial study of magnetic resonance diffusion tensor imaging in brain white matter of early AIDS patients,"Background HIV is a neurotropic virus which can cause brain white matter demyelination, gliosis, and other pathological changes that appear as HIV encephalitis or AIDS dementia. The purpose of this study was to investigate the change of the diffused condition of water molecules in brain white matter in early acquired immune deficiency syndrome (AIDS) patients using MR diffusion tensor imaging (DTI). Methods DTI examinations were performed on a Siemens 3.0T MR scanner in 23 AIDS patients with normal brain appearance by conventional MRI and 20 healthy volunteers as the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in nine regions; corpus callosum (CC) knee, CC body, CC splenium, periventricular white matter, frontal lobe white matter, parietal lobe white matter, occipital lobe white matter, and the anterior and posterior limbs of the internal capsule. The mean FA and ADC values from each region were compared in three groups: the symptomatic, asymptomatic and the control. Results The mean FA values were significantly lower and the mean ADC values were significantly higher in all nine regions in patients in the symptomatic group than in the asymptomatic and control group patients. In the asymptomatic group, the mean FA values were significantly lower and the mean ADC values were significantly higher at the CC knee, CC body, CC splenium, periventricular white matter, frontal lobe white matter and parietal lobe white matter, than in the control group. There were no significant differences at other regions between the two groups. Conclusions The diffused changes of water molecules in brain white matter in AIDS patients are related to brain white matter regions. DTI examination can detect the brain white matter lesions early in AIDS patients.",,"Xuan, A.;Wang, G. B.;Shi, D. P.;Xu, J. L.;Li, Y. L.",2013,2013,,0,
263,Association of Magnetic Resonance Imaging Markers of Cerebrovascular Disease Burden and Cognition,"BACKGROUND AND PURPOSE: The present study sought to examine the association between the burden of cerebrovascular disease (CeVD) as assessed by multimodal magnetic resonance imaging and neurocognitive function. METHODS: Cognitively impaired patients and controls were tested on an extensive neuropsychological battery and underwent multimodal brain magnetic resonance imaging. CeVD markers determined from magnetic resonance imaging included the presence of multiple lacunes, multiple cerebral microbleeds, and moderate or severe white matter hyperintensities as markers for small-vessel disease and cortical stroke and intracranial stenosis as markers for large-vessel disease. A weighted CeVD burden score was constructed, and its association with global and domain-specific cognitive performance was investigated. RESULTS: A total of 305 cases and 94 controls were included in the analysis. A graded association of CeVD burden with neurocognitive function was found. Moreover, a clear threshold of CeVD burden was associated with severe impairment. White matter hyperintensities was associated with global neurocognitive deficits, whereas microbleeds were associated with domain-specific impairments. CONCLUSIONS: The weighted CeVD burden score comprising markers of both small- and large-vessel diseases were associated with deficits in both global and domain-specific neurocognitive function. Additional studies are needed to validate the use of this CeVD burden score for the prediction of dementia.","Aged;Case-Control Studies;Cerebrovascular Disorders/ complications/ pathology;Cognition Disorders/ etiology/pathology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuroimaging/ methods;Neuropsychological Tests","Xu, X.;Hilal, S.;Collinson, S. L.;Chong, E. J.;Ikram, M. K.;Venketasubramanian, N.;Chen, C. L.",2015,Oct,10.1161/strokeaha.115.010700,0,
264,Diffusion tensor imaging changes correlate with cognition better than conventional MRI findings in patients with subcortical ischemic vascular disease,"BACKGROUND/AIMS: To investigate whether diffusion tensor imaging (DTI) is more sensitive than conventional MRI at detecting cognitive deterioration in patients with subcortical ischemic vascular disease (SIVD). METHODS: Forty-two SIVD patients had a diagnosis of no cognitive impairment (NCI), vascular cognitive impairment/no dementia or vascular dementia (VaD). Whole-brain DTI histography and routine MRI were performed on these participants. RESULTS: There were significant differences between cognitively impaired patients and NCI subjects in mean diffusivity and fractional anisotropy in either whole-brain white matter (WBWM) or in normal-appearing white matter (NAWM). All DTI indices within either WBWM or NAWM were found to be significantly correlated with both the attention-executive and memory measures in SIVD subjects. Lacune numbers and T(2)-weighted lesions correlated only with attention-executive measures, whereas hippocampal volumes correlated only weakly with memory measures. Whole-brain gray matter volumes correlated with Z scores for all cognitive domains but language. After VaD patients had been excluded from the analysis, cognitive measures remained significantly correlated with some of the DTI indices, but not with conventional MRI findings. CONCLUSIONS: Compared with conventional MRI, whole-brain DTI is a more reliable and sensitive technique for the early detection of cognitive impairment in SIVD patients.","Aged;Aged, 80 and over;Analysis of Variance;Attention;Brain/pathology/ radiography;Case-Control Studies;Cerebral Infarction/complications/ pathology/radiography;Cognition;Cognition Disorders/complications/ pathology/radiography;Dementia, Vascular/complications/ pathology/radiography;Diffusion Tensor Imaging;Executive Function;Female;Humans;Magnetic Resonance Imaging;Male;Mental Recall;Middle Aged","Xu, Q.;Zhou, Y.;Li, Y. S.;Cao, W. W.;Lin, Y.;Pan, Y. M.;Chen, S. D.",2010,,10.1159/000320491,0,
265,Distinctive RNA expression profiles in blood associated with white matter hyperintensities in brain,"Background and Purpose- White matter hyperintensities (WMH) are areas of high signal detected by T2 and fluid-attenuated inversion recovery sequences on brain MRI. Although associated with aging, cerebrovascular risk factors, and cognitive impairment, the pathogenesis of WMH remains unclear. Thus, RNA expression was assessed in the blood of individuals with and without extensive WMH to search for evidence of oxidative stress, inflammation, and other abnormalities described in WMH lesions in brain. Methods- Subjects included 20 with extensive WMH (WMH+), 45% of whom had Alzheimer disease, and 18 with minimal WMH (WMH-), 44% of whom had Alzheimer disease. All subjects were clinically evaluated and underwent quantitative MRI. Total RNA from whole blood was processed on human whole genome Affymetrix HU133 Plus 2.0 microarrays. RNA expression was analyzed using an analysis of covariance. Results- Two hundred forty-one genes were differentially regulated at ±1.2-fold difference (P<0.005) in subjects with WMH+ as compared to WMH-, regardless of cognitive status and 50 genes were differentially regulated with ±1.5-fold difference (P<0.005). Cluster and principal components analyses showed that the expression profiles for these genes distinguished WMH+ from WMH- subjects. Function analyses suggested that WMH-specific genes were associated with oxidative stress, inflammation, detoxification, and hormone signaling, and included genes associated with oligodendrocyte proliferation, axon repair, long-term potentiation, and neurotransmission. Conclusions- The unique RNA expression profile in blood associated with WMH is consistent with roles of systemic oxidative stress and inflammation, as well as other potential processes in the pathogenesis or consequences of WMH. © 2010 American Heart Association, Inc.",RNA;aged;Alzheimer disease;analysis of covariance;article;brain blood flow;brain damage;cell proliferation;clinical article;clinical evaluation;cluster analysis;cognition;controlled study;detoxification;disease association;encephalitis;female;gene cluster;gene control;gene expression;genome;human;long term potentiation;male;microarray analysis;nerve fiber;nerve regeneration;neurotransmission;nuclear magnetic resonance imaging;oligodendroglia;oxidative stress;pathogenesis;principal component analysis;priority journal;quantitative analysis;white matter,"Xu, H.;Stamova, B.;Jickling, G.;Tian, Y.;Zhan, X.;Ander, B. P.;Liu, D.;Turner, R.;Rosand, J.;Goldstein, L. B.;Furie, K. L.;Verro, P.;Johnston, S. C.;Sharp, F. R.;Decarli, C. S.",2010,,,0,
266,Reliability and precision of pseudo-continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O-water PET in elderly subjects at risk for Alzheimer's disease,"Arterial spin labeling (ASL) offers MRI measurement of cerebral blood flow (CBF) in vivo, and may offer clinical diagnostic utility in populations such as those with early Alzheimer's disease (AD). In the current study, we investigated the reliability and precision of a pseudo-continuous ASL (pcASL) sequence that was performed two or three times within one hour on eight young normal control subjects, and 14 elderly subjects including 11 with normal cognition, one with AD and two with Mild Cognitive Impairment (MCI). Six of these elderly subjects including one AD, two MCIs and three controls also received (15)O-water positron emission tomography (PET) scans 2 h before their pcASL MR scan. The instrumental reliability of pcASL was evaluated with the intraclass correlation coefficient (ICC). The ICCs were greater than 0.90 in pcASL global perfusion measurements for both the young and the elderly groups. The cross-modality perfusion imaging comparison yielded very good global and regional agreement in global gray matter and the posterior cingulate cortex. Significant negative correlation was found between age and the gray/white matter perfusion ratio (r = -0.62, p < 0.002). The AD and MCI patients showed the lowest gray/white matter perfusion ratio among all the subjects. The data suggest that pcASL provides a reliable whole brain CBF measurement in young and elderly adults whose results converge with those obtained with the traditional (15)O-water PET perfusion imaging method. pcASL perfusion MRI offers an alternative method for non-invasive in vivo examination of early pathophysiological changes in AD.","Adult;Aged;Alzheimer Disease/ diagnosis;Arteries/ metabolism;Brain/pathology;Brain Mapping;Cerebrovascular Circulation/physiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Oxygen Radioisotopes;Perfusion;Positron-Emission Tomography;Reproducibility of Results;Risk Factors;Spin Labels;Water/ metabolism;Young Adult","Xu, G.;Rowley, H. A.;Wu, G.;Alsop, D. C.;Shankaranarayanan, A.;Dowling, M.;Christian, B. T.;Oakes, T. R.;Johnson, S. C.",2010,Apr,10.1002/nbm.1462,0,
267,Atorvastatin therapy is associated with greater and faster cerebral hemodynamic response,"Hypercholesterolemia in midlife increases the risk of subsequent cognitive decline, neurovascular disease, and Alzheimer's disease (AD), and statin use is associated with reduced prevalence of these outcomes. While statins improve vasoreactivity in peripheral arteries and large cerebral arteries, little is known about the effects of statins on cerebral hemodynamic responses and cognition in healthy asymptomatic adults. At the final visit of a 4-month randomized, controlled, double-blind study comparing atorvastatin 40 mg daily to placebo, 16 asymptomatic middle-aged adults (15 had useable data) underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) quantitative cerebral blood flow (qCBF), dynamic susceptibility contrast (DSC) and structural imagings of the brain. Using a memory recognition task requiring discrimination of previously viewed (PV) and novel (NV) human faces, fMRI was used to elicit activation from brain regions known to be vulnerable to changes associated with AD. The BOLD signal amplitude (PV > NV) and latency to each stimulus were tested on a voxel basis between the atorvastatin (n=8) and placebo (n=7) groups. Persons randomized to atorvastatin not only showed significantly greater BOLD amplitude in the right angular gyrus, left superior parietal lobule, right middle temporal and superior sulcus than the placebo group, but also decreased hemodynamic response latencies in the right middle frontal gyrus, left precentral gyrus, left cuneus and right posterior middle frontal gyrus. However, neither the resting cerebral blood flow (CBF) measured with ASL nor the mean transit time (MTT) of cerebral perfusion calculated from DSC showed differences in these regions in either group. The drug related BOLD differences during memory recognition suggest that atorvastatin may have improved cerebral small vessel vasoreactivity, possibly through an effect on endothelial function. Furthermore, these results suggest that the effect of atorvastatin on the task-induced BOLD signal may not be a simple consequence of baseline flow change.",,"Xu, G.;Fitzgerald, M. E.;Wen, Z.;Fain, S. B.;Alsop, D. C.;Carroll, T.;Ries, M. L.;Rowley, H. A.;Sager, M. A.;Asthana, S.;Johnson, S. C.;Carlsson, C. M.",2008,Jun 1,10.1007/s11682-007-9019-7,0,
268,Operational definitions improve reliability of the age-related white matter changes scale,"BACKGROUND AND PURPOSE: Although the age-related white matter changes (ARWMC) scale has been advocated to be applicable to both MRI and CT for assessing the severity of WMC, its inter-rater reliability on CT is only fair. We aimed to operationalize the ARWMC scale and investigate the effect of this operationalization on the reliability and validity on MRI and CT. METHODS: Operational definitions of the ARWMC scale were derived from Erkinjuntti research criteria for subcortical vascular dementia and Scheltens scale. Using original and operationalized ARWMC scale, eight observers recorded the time for rating per MRI and per CT. We investigated the inter-rater and intrarater reliability as well as validity against volume using data from 97 stroke patients. RESULTS: Inter-rater reliability of the operationalized scale on CT (0.874, 95% confidence interval [0.780-0.934]) was better than the original scale (0.569, 95% confidence interval [0.247-0.775]). Its intrarater reliability on CT (0.869) and reliability on MRI (inter-rater: 0.860; intrarater: 0.838) was comparable with the original scale (CT intrarater: 0.750 and on MRI inter-rater: 0.845; intrarater: 0.853). The time required to administer the operationalized scale (4'2'' for MRI and 1'18'' for CT) was similar to that of the original scale (3'56'' for MRI and 1'16'' for CT). The original scale and operationalized scale also significantly correlated with WMC volume (operationalized scale rho = 0.613, P < 0.001, original scale rho = 0.638, P < 0.001). CONCLUSION: Operational definitions improve the inter-rater reliability of ARWMC scale on CT, and it correlates with volumetric measurement.","Aged;Aged, 80 and over;Aging/*pathology;Cognition Disorders/*pathology/radiography;Dementia/*pathology/radiography;Diagnostic Imaging/methods/*standards;Disease Progression;Female;Humans;Male;Nerve Fibers, Myelinated/*pathology;Predictive Value of Tests;*Severity of Illness Index","Xiong, Y.;Yang, J.;Wong, A.;Wong, C. H.;Chan, S. S.;Li, H. H.;Tam, L. H.;Bao, J. W.;Wong, G. C.;Chen, X.;Chu, W. C.;Lee, W. K.;Wong, K. S.;Mok, V. C.",2011,May,10.1111/j.1468-1331.2010.03272.x,0,
269,"Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities","Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 +/- 4.52 cm(3) vs 5.01 +/- 6.00 cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (beta = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; beta = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.",Aged;Cerebral Cortex/blood supply/ pathology;Cerebral Small Vessel Diseases/complications/drug therapy/ pathology;Cognition Disorders/drug therapy/etiology;Disease Progression;Female;Folic Acid/therapeutic use;Humans;Magnetic Resonance Imaging;Male;Stroke/ complications;Vitamin B 12/therapeutic use;Vitamin B 6/therapeutic use;White Matter/ pathology,"Xiong, Y.;Wong, A.;Cavalieri, M.;Schmidt, R.;Chu, W. W.;Liu, X.;Wong, K. S.;Mok, V.",2014,Jul,10.1007/s13311-014-0270-5,0,
270,A Diffusion Tensor Imaging Study on White Matter Abnormalities in Patients with Type 2 Diabetes Using Tract-Based Spatial Statistics,"BACKGROUND AND PURPOSE: Patients with type 2 diabetes mellitus have considerably higher risk of developing cognitive impairment and dementia. WM changes in these patients have been reported. Our aim was to demonstrate that gradual and continuous WM change and the associated cognitive decline in patients with type 2 diabetes mellitus can be captured by DTI parameters, which can be used to complement neuropsychological test scores in identifying patients with type 2 diabetes mellitus with and without mild cognitive impairment. MATERIALS AND METHODS: Forty-two patients with type 2 diabetes mellitus, divided into a group with mild cognitive impairment (n = 20) and a group with normal cognition (n = 22), were enrolled with age-, sex-, and education-matched healthy controls (n = 26). 3T DTI followed by Tract-Based Spatial Statistics analysis was used to investigate the differences in fractional anisotropy, mean diffusivity, axial diffusivity (lambda1), and radial diffusivity (lambda23) among the groups. A receiver operating characteristic analysis assessed the performance of DTI parameters for separating the 2 groups with type 2 diabetes mellitus. RESULTS: The whole-brain Tract-Based Spatial Statistics analysis revealed that 7.3% and 24.9% of the WM exhibited decreased fractional anisotropy and increased mean diffusivity (P < .05), respectively, between the diabetes mellitus with mild cognitive impairment and the diabetes mellitus with normal cognition groups, while considerably larger WM regions showed fractional anisotropy (36.6%) and mean diffusivity (58.8%) changes between the diabetes mellitus with mild cognitive impairment and the healthy control groups. These changes were caused primarily by an elevated radial diffusivity observed in the patients with diabetes mellitus with mild cognitive impairment. Radial diffusivity also exhibited subtle but statistically significant changes between the diabetes mellitus with normal cognition and the healthy control groups. Analyses on individual fiber tracts showed pronounced fractional anisotropy reduction and mean diffusivity elevation in regions related to cognitive functions. The receiver operating characteristic analysis on the right cingulum (hippocampus) showed that fractional anisotropy produced a larger area under the curve (0.832) than mean diffusivity (0.753) for separating mild cognitive impairment from normal cognition among patients with type 2 diabetes mellitus. When fractional anisotropy was combined with mean diffusivity, the area under the curve was further improved to 0.857. CONCLUSIONS: DTI parameters can show a substantial difference between patients with type 2 diabetes mellitus with and without mild cognitive impairment, suggesting their potential use as an imaging marker for detecting cognitive decline in patients with type 2 diabetes mellitus. More important, DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in patients with type 2 diabetes mellitus before they can be diagnosed clinically by using conventional neuropsychological tests.","Adult;Aged;Area Under Curve;Brain/diagnostic imaging/pathology;Cognition Disorders/ etiology;Diabetes Mellitus, Type 2/ complications/ diagnostic imaging/pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Middle Aged;ROC Curve;White Matter/ diagnostic imaging/pathology","Xiong, Y.;Sui, Y.;Xu, Z.;Zhang, Q.;Karaman, M. M.;Cai, K.;Anderson, T. M.;Zhu, W.;Wang, J.;Zhou, X. J.",2016,Aug,,0,
271,A Diffusion Tensor Imaging Study on White Matter Abnormalities in Patients with Type 2 Diabetes Using Tract-Based Spatial Statistics,"BACKGROUND AND PURPOSE: Patients with type 2 diabetes mellitus have considerably higher risk of developing cognitive impairment and dementia. WM changes in these patients have been reported. Our aim was to demonstrate that gradual and continuous WM change and the associated cognitive decline in patients with type 2 diabetes mellitus can be captured by DTI parameters, which can be used to complement neuropsychological test scores in identifying patients with type 2 diabetes mellitus with and without mild cognitive impairment. MATERIALS AND METHODS: Forty-two patients with type 2 diabetes mellitus, divided into a group with mild cognitive impairment (n = 20) and a group with normal cognition (n = 22), were enrolled with age-, sex-, and education-matched healthy controls (n = 26). 3T DTI followed by Tract-Based Spatial Statistics analysis was used to investigate the differences in fractional anisotropy, mean diffusivity, axial diffusivity (lambda1), and radial diffusivity (lambda23) among the groups. A receiver operating characteristic analysis assessed the performance of DTI parameters for separating the 2 groups with type 2 diabetes mellitus. RESULTS: The whole-brain Tract-Based Spatial Statistics analysis revealed that 7.3% and 24.9% of the WM exhibited decreased fractional anisotropy and increased mean diffusivity (P < .05), respectively, between the diabetes mellitus with mild cognitive impairment and the diabetes mellitus with normal cognition groups, while considerably larger WM regions showed fractional anisotropy (36.6%) and mean diffusivity (58.8%) changes between the diabetes mellitus with mild cognitive impairment and the healthy control groups. These changes were caused primarily by an elevated radial diffusivity observed in the patients with diabetes mellitus with mild cognitive impairment. Radial diffusivity also exhibited subtle but statistically significant changes between the diabetes mellitus with normal cognition and the healthy control groups. Analyses on individual fiber tracts showed pronounced fractional anisotropy reduction and mean diffusivity elevation in regions related to cognitive functions. The receiver operating characteristic analysis on the right cingulum (hippocampus) showed that fractional anisotropy produced a larger area under the curve (0.832) than mean diffusivity (0.753) for separating mild cognitive impairment from normal cognition among patients with type 2 diabetes mellitus. When fractional anisotropy was combined with mean diffusivity, the area under the curve was further improved to 0.857. CONCLUSIONS: DTI parameters can show a substantial difference between patients with type 2 diabetes mellitus with and without mild cognitive impairment, suggesting their potential use as an imaging marker for detecting cognitive decline in patients with type 2 diabetes mellitus. More important, DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in patients with type 2 diabetes mellitus before they can be diagnosed clinically by using conventional neuropsychological tests.",,"Xiong, Y.;Sui, Y.;Xu, Z.;Zhang, Q.;Karaman, M. M.;Cai, K.;Anderson, T. M.;Zhu, W.;Wang, J.;Zhou, X. J.",2016,Mar 17,10.3174/ajnr.A4740,0,270
272,The age-related white matter changes scale correlates with cognitive impairment,"Background and purpose: Age-related white matter changes (ARWMC) are closely associated with cognitive impairment. Although the ARWMC scale has been widely used to grade white matter changes (WMC) severity, the correlation between this scale and cognitive impairment has not been studied. We aimed to validate the ARWMC scale against cognition in patients with stroke.Methods: We determined the severity of WMC for 172 patients with stroke on MRI by volumetric quantification and the ARWMC scale. Two scores (total score and global score) were derived from the ARWMC scale. We assessed executive function and global cognition using the Mattis dementia rating scale-initiation/perseveration subset (MDRS I/P) and mini-mental state examination (MMSE), respectively. We investigated the association between the three WMC measures (volume, total score, and global score) and clinical variables with cognitive impairment using multivariate regression analysis.Results: Even after adjusting for other clinical variables, total score and global score of ARWMC scale were independently associated with MDRS I/P (beta = -0.248, P = 0.001 and beta = -0.218, P = 0.005, respectively) and MMSE (adjusted odds ratio 1.181, 95%CI [1.038-1.343] and adjusted odds ratio 1.740, 95%CI [1.063-2.847], respectively).Conclusion: The ARWMC scale correlates well with cognitive impairment in patients with stroke. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.",age related white matter changes;aged;article;cognition;cognitive defect;controlled study;dementia;disease severity;female;human;major clinical study;male;Mini Mental State Examination;multiple regression;nuclear magnetic resonance imaging;priority journal;rating scale;cerebrovascular accident;validation study;volumetry;white matter,"Xiong, Y.;Mok, V.;Wong, A.;Chen, X.;Chu, W. C. W.;Fan, Y.;Soo, Y.;Wong, K. S.",2010,,,0,
273,Cognitive Profile and its Association with Neuroimaging Markers of Non-Demented Cerebral Amyloid Angiopathy Patients in a Stroke Unit,"BACKGROUND: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized. OBJECTIVE: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA. METHODS: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed. RESULTS: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of -1.92+/-1.56 (mean+/-SD), then followed by executive function (-0.93+/-1.01), episodic memory (-0.87+/-1.29), semantic fluency (-0.73+/-1.06), and attention (-0.42+/-0.98). TBV of the CAA patients was correlated with processing speed (beta= 0.335, p = 0.03) and executive function (beta= 0.394, p = 0.01). CONCLUSIONS: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function.",Aged;Atrophy/diagnostic imaging/psychology;Brain/ diagnostic imaging;Cerebral Amyloid Angiopathy/complications/ diagnostic imaging/ psychology/therapy;Cognition;Cognition Disorders/diagnostic imaging/etiology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Stroke/therapy;Brain atrophy;cerebral amyloid angiopathy;cerebral microbleeds;clinical neuropsychology;cognitive impairment;hippocampal atrophy;intracranial hemorrhage;white matter hyperintensities,"Xiong, L.;Davidsdottir, S.;Reijmer, Y. D.;Shoamanesh, A.;Roongpiboonsopit, D.;Thanprasertsuk, S.;Martinez-Ramirez, S.;Charidimou, A.;Ayres, A. M.;Fotiadis, P.;Gurol, E.;Blacker, D. L.;Greenberg, S. M.;Viswanathan, A.",2016,Mar 08,,0,
274,Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage,"Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%-23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01-1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97-6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26-2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20-1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.",Amyloid angiopathy;cerebrovascular disease;dementia;magnetic resonance imaging,"Xiong, L.;Boulouis, G.;Charidimou, A.;Roongpiboonsopit, D.;Jessel, M. J.;Pasi, M.;Reijmer, Y. D.;Fotiadis, P.;Ayres, A.;Merrill, E.;Schwab, K.;Blacker, D.;Gurol, M. E.;Greenberg, S. M.;Viswanathan, A.",2018,Feb,,0,275
275,Dementia incidence and predictors in cerebral amyloid angiopathy patients without intracerebral hemorrhage,"Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%-23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01-1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97-6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26-2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20-1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.",Amyloid angiopathy;cerebrovascular disease;dementia;magnetic resonance imaging,"Xiong, L.;Boulouis, G.;Charidimou, A.;Roongpiboonsopit, D.;Jessel, M. J.;Pasi, M.;Reijmer, Y. D.;Fotiadis, P.;Ayres, A.;Merrill, E.;Schwab, K.;Blacker, D.;Gurol, M. E.;Greenberg, S. M.;Viswanathan, A.",2017,Jan 01,,0,
276,Clinical characteristics of X-linked adrenoleukodystrophy,"OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is a genetically determined disorder that involves the nervous system white matter, axons, adrenal cortex and testes. The typical clinical manifestations are progressive psychomotor regression, vision and/or auditory impairment and adrenal insufficiency. The clinical manifestation, biochemical change and genetic counseling work of X-linked ALD were analyzed. METHODS: The clinical features of 29 cases with ALD were summarized and analyzed, including symptoms and signs, measurement of blood very long chain fatty acids (VLCFA), adrenal function, cranial magnetic resonance imaging (MRI) and pedigree investigation. RESULTS: Among these 29 cases, the clinical phenotype could be classified into childhood cerebral (22 cases), adolescent cerebral (4 cases), adrenomyeloneuropathic (1 case), Addison's disease (1 case) and asymptomatic or presymptomatic (1 case) types. Nine of them had positive family history. Pedigree investigation was consistent with typical sex-linked recessive inheritance. There were 45 ALD patients in these 29 pedigrees. The neurological manifestations varied among members of the same family. Nine cases died during follow up. The causes of death were central respiratory failure or other complications of ALD and so on. Laboratory tests demonstrated abnormally high plasma levels of VLCFA in ALD patients; MRI demonstrated symmetric butterfly-like low T(1) and high T(2) signals in the parieto-occipital white matter. The impairment in the splenium of corpus callosum made the bilateral lesion region converge into one. It could progress anteriorly and injure the bilateral posterior limb of internal capsule and the temporal lobe, and could injure the brainstem inferiorly. Following intravenous injection of contrast material, thin stripe of lacelike enhancement could be observed. CONCLUSIONS: The atypical initial symptom of ALD was seizures. The MRI showed abnormal signal in the cerebellar white matter. This disease can influence the normal development of children, this was more pronounced in the childhood cerebral ALD type. It tended to progress rapidly with dementia, vegetative state or death. Since antenatal diagnostic method is available now, emphasis should be made on the antenatal examination in order to make an early diagnosis and abort pregnancy if necessary.",,"Xiong, H.;Zhang, Y. H.;Qin, J.;Xiao, J. X.;Shi, C. Y.;Zhou, S. M.;Wu, X. R.",2003,Mar,,0,
277,Role of family history for Alzheimer biomarker abnormalities in the adult children study,"OBJECTIVE: To assess whether family history (FH) of Alzheimer disease (AD) alone influences AD biomarker abnormalities. DESIGN: Adult Children Study. SETTING: Washington University's Charles F. and Joanne Knight Alzheimer's Disease Research Center. PARTICIPANTS: A total of 269 cognitively normal middle- to older-aged individuals with and without an FH for AD. MAIN OUTCOME MEASURES: Clinical and cognitive measures, magnetic resonance imaging-based brain volumes, diffusion tensor imaging-based white matter microstructure, cerebrospinal fluid biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography using the [(11)C] benzothiazole tracer, Pittsburgh compound B. RESULTS: A positive FH for AD was associated with an age-related decrease of cerebrospinal fluid Abeta42; the epsilon4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted cerebrospinal fluid Abeta42 was decreased for individuals with APOE4 compared with the level for those without, and the decrease was larger for individuals with a positive FH compared with the decrease for those without. The variation of cerebrospinal fluid tau and Pittsburgh compound B mean cortical binding potential increased by age. For individuals younger than 55, an age-related increase in mean cortical binding potential was associated with APOE4 but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in mean cortical binding potential. A positive FH was associated with decreased fractional anisotropy from diffusion tensor imaging in the genu and splenium of the corpus callosum. CONCLUSION: Independent of APOE4, FH is associated with age-related change of several cerebrospinal fluid, Pittsburgh compound B, and diffusion tensor imaging biomarkers in cognitively normal middle- to older-aged individuals, suggesting that non- APOE susceptibility genes for AD influence AD biomarkers.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/complications/ diagnosis/genetics/ metabolism;Amyloid beta-Peptides/cerebrospinal fluid;Aniline Compounds;Apolipoprotein E4/genetics;Attention/physiology;Biomarkers/ metabolism;Brain/pathology/radionuclide imaging;Carbon Radioisotopes;Cognition Disorders/diagnosis/etiology;Cohort Studies;Disease Progression;Family Health;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Peptide Fragments/cerebrospinal fluid;Positron-Emission Tomography;Psychiatric Status Rating Scales;Reaction Time/physiology;Residence Characteristics;Statistics as Topic;Thiazoles","Xiong, C.;Roe, C. M.;Buckles, V.;Fagan, A.;Holtzman, D.;Balota, D.;Duchek, J.;Storandt, M.;Mintun, M.;Grant, E.;Snyder, A. Z.;Head, D.;Benzinger, T. L.;Mettenburg, J.;Csernansky, J.;Morris, J. C.",2011,Oct,10.1001/archneurol.2011.208,0,
278,Correlation analysis of early prognosis of progressive neurological deterioration and cerebral watershed infarction: A clinical study,"Objective: To investigate the effect of progressive neurological deterioration (PND) of cerebral watershed infarction on early prognosis.Methods: The consecutive patients with cerebral watershed infarction admitted in the Department of Neurology, Jinling Hospital, Nanjing University School of Medicine and their cerebral watershed infarctions confirmed by the imaging examination from March 2009 to March 2014 were enrolled. The clinical features, laboratory indicators and imaging features of internal watershed infarction, cortical-type watershed infarction, and mixed watershed infarction were identified and analyzed. The National Institutes of Health Stroke Scale was used to score neurological deficit. The modified Rankin scale (mRS) was used to score the prognosis of patients. Single factor analysis was used to compare the differences between the groups. At the same time, the correlation between PND and poor prognosis of cerebral watershed infarction at day 90 was analyzed by multivariable Logistic regression analysis.Results: A total of 89 patients with cerebral watershed infarction were enrolled, including 43 cortical-type watershed infarctions, 36 internal watershed infarctions, and 10 mixed watershed infarctions. Single factor analysis indicated that the incidences of PND of internal watershed infarction and mixed watershed infarction were significantly higher than the cortical-type watershed infarction (36.1% [n = 13], 50.0% [n = 5], and 16.3% [n =7], respectively; P =0. 018). At day 90,28 patients had poor prognosis, and mRS was (3.4 ± 1.0) scores at day 90. There was significant difference in the types of infarction between the patients with poor prognosis and patients with good prognosis (P < 0.05). In patients with poor prognosis, most of them were internal watershed infarctions, accounting for 50. 0% (14/28), while in patients with good prognosis, most of them were cortical-type watershed infarctions(57.4% [35/61]). The incidence of PND in patients with poor prognosis was significantly higher than that in patients with good prognosis (57. 1% [16/28] vs. 14. 8% [9/61]; P < 0. 05). The result of multivariate Logistic regression analysis showed that after adjustment for confounding factor, PND was independently associated with the poor prognosis of cerebral watershed infarction at day 90 (OR 6. 969,95% CI 2. 451-19. 869; P < 0. 01).Conclusion: Compared with the cortical-type watershed infarction, the patients with internal watershed infarction is more prone to have PND, and PND is independently correlate with the poor prognosis at day 90.",,"Xie, Y.;Zhang, X. H.;Qiu, Z. M.;Zhang, J.;Yang, L.;Xie, X.;Ma, N.;Liu, X. F.",2014,1,,0,
279,Identification of Amnestic Mild Cognitive Impairment Using Multi-Modal Brain Features: A Combined Structural MRI and Diffusion Tensor Imaging Study,"Identifying amnestic mild cognitive impairment (aMCI) is of great clinical importance because aMCI is a putative prodromal stage of Alzheimer's disease. The present study aimed to explore the feasibility of accurately identifying aMCI with a magnetic resonance imaging (MRI) biomarker. We integrated measures of both gray matter (GM) abnormalities derived from structural MRI and white matter (WM) alterations acquired from diffusion tensor imaging at the voxel level across the entire brain. In particular, multi-modal brain features, including GM volume, WM fractional anisotropy, and mean diffusivity, were extracted from a relatively large sample of 64 Han Chinese aMCI patients and 64 matched controls. Then, support vector machine classifiers for GM volume, FA, and MD were fused to distinguish the aMCI patients from the controls. The fused classifier was evaluated with the leave-one-out and the 10-fold cross-validations, and the classifier had an accuracy of 83.59% and an area under the curve of 0.862. The most discriminative regions of GM were mainly located in the medial temporal lobe, temporal lobe, precuneus, cingulate gyrus, parietal lobe, and frontal lobe, whereas the most discriminative regions of WM were mainly located in the corpus callosum, cingulum, corona radiata, frontal lobe, and parietal lobe. Our findings suggest that aMCI is characterized by a distributed pattern of GM abnormalities and WM alterations that represent discriminative power and reflect relevant pathological changes in the brain, and these changes further highlight the advantage of multi-modal feature integration for identifying aMCI.",,"Xie, Y.;Cui, Z.;Zhang, Z.;Sun, Y.;Sheng, C.;Li, K.;Gong, G.;Han, Y.;Jia, J.",2015,,10.3233/jad-150184,0,
280,Quantitative MR measures in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationships with clinical scales,"Objective: To analyze white matter hyperintensities (WMH) and brain volumes quantitatively in patients with Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) on conventional MRI and correlate them with clinical parameters. Methods: Fifteen patients with CADASIL confirmed by pathological investigation underwent conventional MRI examinations. Involvement of centrum semiovale, posterior limbs of the internal capsule, corpus callosum, external capsules and white matter of the temporal poles was determined by an experienced radiologist. Normalized brain volume (NBV) and the percentage of WMH to brain volume were calculated with softwares and they were correlated with NIHSS and MMSE statistically. Results: Involvement of white matter in the brains of patients with CADASIL included: semiovale centrum in 13 cases, white matter of the temporal poles in 10 cases, external capsules in 8 cases, posterior limbs of the internal capsule in 5 cases, corpus callosum in 4 cases. The percentage of WMH to brain volume was (5.7 ± 1.4)%, and the NBV was (1602 ± 58) × 103 mm3. Spearman test showed a significant relationship between age and NBV (r = -0.555, P <0.05). There was a significant relationship between NBV and NIHSS (r = -0.624, P < 0.05). The percentage of WMH to brain volume correlated significantly with NIHSS and MMSE (r = 0.522, P <0.05; r = - 0.679, P <0.01). Conclusions: The white matter hyperintensities and brain volume in patients with CADASIL can be assessed quantitatively, which showed correlation with severity of the clinical scale. The development of WMH may refleet the degree of cognitive impairment in CADASIL.",adult;age distribution;article;brain size;CADASIL;capsula interna;clinical article;clinical study;cognitive defect;computer program;controlled study;corpus callosum;correlation coefficient;disease severity;female;histopathology;human;male;Mini Mental State Examination;National Institutes of Health Stroke Scale;nuclear magnetic resonance imaging;quantitative analysis;temporal lobe;white matter,"Xie, S.;Xiao, J. X.;Liu, Y.;Yuan, Y.",2008,,,0,
281,Voxel-based detection of white matter abnormalities in mild Alzheimer disease,"OBJECTIVE: To detect white matter abnormalities in patients with mild Alzheimer disease (AD) by diffusion tensor imaging and to determine their topographic relationship with gray matter atrophy. METHODS: Thirteen patients with mild AD and 16 normal age-matched volunteers underwent diffusion tensor imaging and three-dimensional spoiled gradient-recalled sequence scanning. Voxel-based morphometry was conducted to detect regions of gray matter atrophy in the AD group relative to the control group. Fractional anisotropy (FA) maps were processed using SPM2 to make voxel-wise comparison of anisotropy in whole brain between the two groups. The relationship between locations of abnormalities in the white and gray matter was examined. RESULTS: Significant reductions in anisotropy were found in the white matter of both medial temporal lobes, bilateral temporal stems, bilateral superior longitudinal fasciculi, bilateral internal capsules, and cerebral peduncles, as well as the white matter of left middle temporal gyrus and right superior parietal lobule, the body and genu of the corpus callosum, and the right lateral capsule in patients with AD. Although the decrease in FA was consistent with cortical volumetric reduction in both temporal lobes, the widespread involvement of bilateral superior longitudinal fasciculi was dominant in these white matter findings. CONCLUSIONS: Voxel-wise comparison of whole-brain anisotropy revealed widely distributed disintegration of white matter in mild Alzheimer disease (AD). The white matter shows a different pattern of degeneration from gray matter and may be an independent factor in the progress of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ classification/ diagnosis;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity;Severity of Illness Index;Signal Processing, Computer-Assisted;Subtraction Technique","Xie, S.;Xiao, J. X.;Gong, G. L.;Zang, Y. F.;Wang, Y. H.;Wu, H. K.;Jiang, X. X.",2006,Jun 27,10.1212/01.wnl.0000219625.77625.aa,0,
282,Peroxisome-proliferator-activated receptor gamma coactivator 1 alpha contributes to dysmyelination in experimental models of Huntington's disease,"The peroxisome-proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha) has been implicated in the pathogenesis of several neurodegenerative disorders, including Huntington's disease (HD). Recent data demonstrating white matter abnormalities in PGC1alpha knock-out (KO) mice prompted us to examine the role of PGC1alpha in CNS myelination and its relevance to HD pathogenesis. We found deficient postnatal myelination in the striatum of PGC1alpha KO mice, accompanied by a decrease in myelin basic protein (MBP). In addition, brain cholesterol, its precursors, and the rate-limiting enzymes for cholesterol synthesis, HMG CoA synthase (HMGCS1) and HMG CoA reductase (HMGCR), were also reduced in PGC1alpha KO mice. Moreover, knockdown of PGC1alpha in oligodendrocytes by lentiviral shRNA led to a decrease in MBP, HMGCS1, and Hmgcr mRNAs. Chromatin immunoprecipitations revealed the recruitment of PGC1alpha to MBP promoter in mouse brain, and PGC1alpha over-expression increased MBP and SREBP-2 promoter activity, suggesting that PGC1alpha regulates MBP and cholesterol synthesis at the transcriptional level. Importantly, expression of mutant huntingtin (Htt) in primary oligodendrocytes resulted in decreased expression of PGC1alpha and its targets HmgcS1, Hmgcr, and MBP. Decreased expression of MBP and deficient myelination were found postnatally and in adult R6/2 mouse model of HD. Diffusion tensor imaging detected white matter abnormalities in the corpus callosum of R6/2 mice, and electron microscopy revealed thinner myelin sheaths and increased myelin periodicity in BACHD [bacterial artificial chromosome (BAC)-mediated transgenic model for Huntington's disease] mice expressing full-length mutant Htt. Together, these data suggest that PGC1alpha plays a role in postnatal myelination and that deficient PGC1alpha activity in oligodendrocytes may contribute to abnormal myelination in HD.","Analysis of Variance;Animals;Blotting, Western;Brain/metabolism/pathology;Chromatin Immunoprecipitation;Demyelinating Diseases/genetics/ metabolism/pathology;Diffusion Tensor Imaging;Disease Models, Animal;Huntington Disease/genetics/ metabolism/pathology;Hydroxymethylglutaryl CoA Reductases/genetics/metabolism;Hydroxymethylglutaryl-CoA Synthase/genetics/metabolism;Immunohistochemistry;Mice;Mice, Knockout;Myelin Basic Protein/genetics/metabolism;Myelin Sheath/ metabolism/pathology;Oligodendroglia/ metabolism/pathology;Reverse Transcriptase Polymerase Chain Reaction;Transcription Factors/genetics/ metabolism","Xiang, Z.;Valenza, M.;Cui, L.;Leoni, V.;Jeong, H. K.;Brilli, E.;Zhang, J.;Peng, Q.;Duan, W.;Reeves, S. A.;Cattaneo, E.;Krainc, D.",2011,Jun 29,10.1523/jneurosci.1291-11.2011,0,
283,"White Matter Changes in Bipolar Disorder, Alzheimer Disease, and Mild Cognitive Impairment: New Insights from DTI","Neuropathological and neuroimaging studies have reported significant changes in white matter in psychiatric and neurodegenerative diseases. Diffusion tensor imaging (DTI), a recently developed technique, enables the detection of microstructural changes in white matter. It is a noninvasive in vivo technique that assesses water molecules' diffusion in brain tissues. The most commonly used parameters are axial and radial diffusivity reflecting diffusion along and perpendicular to the axons, as well as mean diffusivity and fractional anisotropy representing global diffusion. Although the combination of these parameters provides valuable information about the integrity of brain circuits, their physiological meaning still remains controversial. After reviewing the basic principles of DTI, we report on recent contributions that used this technique to explore subtle structural changes in white matter occurring in elderly patients with bipolar disorder and Alzheimer disease.",,"Xekardaki, A.;Giannakopoulos, P.;Haller, S.",2011,,10.4061/2011/286564,0,
284,Analysis of 4 cases with misdiagnosed neurosyphilis and review of literatures,"Objective: To discuss the diagnostic criteria of neurosyphilis, and to decrease the misdiagnosis and missed diagnosis rates of this disease by enriching the physicians with characteristic knowledge of neurosyphilis. Methods: Four cases of misdiagnosed neurosyphilis in our hospital were presented and related literatures were also extensively reviewed in this study. Results: The 4 cases of misdiagnosed neurosyphilis were meningovascular syphilis combined with paralytic dementia, paralytic dementia, tabes dorsalis and syphilitic gumma of myelon which were clinically misdignosed as cerebral infarction, Alzheimer disease (AD), multiple system atrophy and intraspinal tumor, respectively. Totally 29 articles and 132 neurosyphilis cases were reported on the journals of Chinese Medical Association (CMA) collected by Wanfan Data since 2000. There were 106 male cases and 26 female cases. The age of onset of the patients was from 1 to 75 years old, average (44.09 ± 12.93). Among them, 28 cases (21.21%) had a history of syphilis infection, 55 cases (41.67%) admitted a history of unclean coitus, and 35 cases (26.52%) were misdiagnosed or missed diagnosed. The clinical classification of the 132 reported cases included one case (0.76%) of asymptomatic neurosyphilis, 14 cases (10.61%) of cerebrospinal meningitis, 43 cases (32.58%) of meningovascular syphilis, 44 cases (33.33%) of paralytic dementia, 13 cases (9.85%) of tabes dorsalis, 15 cases (11.63%) of syphilitic gumma, and 2 cases (1.51%) of special neurosyphilis, respectively. Conclusion: The clinical characteristics of neurosyphilis are varied, and misdiagnosis and missed diagnosis rate are high at early stage of this disease. There is no golden standard available now in diagnosing. The diagnosis mainly depends on clinical characteristics, and positive findings in serum and cerebrospinal fluid (CSF) examinations, magnetic resonance imaging (MRI) and pathological examination.",,"Wu, Y. W.;Xiao, Q.",2009,October,,0,
285,Presence of lacunar infarctions is associated with the spatial navigation impairment in patients with mild cognitive impairment: a DTI study,"Lacunar cerebral infarction (LI) is one of risk factors of vascular dementia and correlates with progression of cognitive impairment including the executive functions. However, little is known on spatial navigation impairment and its underlying microstructural alteration of white matter in patients with LI and with or without mild cognitive impairment (MCI). Our aim was to investigate whether the spatial navigation impairment correlated with the white matter integrity in LI patients with MCI (LI-MCI). Thirty patients with LI were included in the study and were divided into LI-MCI (n=17) and non MCI (LI-Non MCI) groups (n=13) according neuropsychological tests.The microstructural integrity of white matter was assessed by calculating a fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) scans. The spatial navigation accuracy, separately evaluated as egocentric and allocentric, was assessed by a computerized human analogue of the Morris Water Maze tests Amunet. LI-MCI performed worse than the CN and LI-NonMCI groups on egocentric and delayed spatial navigation subtests. LI-MCI patients have spatial navigation deficits. The microstructural abnormalities in diffuse brain regions, including hippocampus, uncinate fasciculus and other brain regions may contribute to the spatial navigation impairment in LI-MCI patients at follow-up.",Gerotarget;diffusion tensor imaging;lacunar infarction;mild cognitive impairment;spatial navigation,"Wu, Y. F.;Wu, W. B.;Liu, Q. P.;He, W. W.;Ding, H.;Nedelska, Z.;Hort, J.;Zhang, B.;Xu, Y.",2016,Nov 29,,0,
286,Diffusion alterations in corpus callosum of patients with HIV,"BACKGROUND AND PURPOSE: Diffusion alterations have been identified in the corpus callosum and frontal white matter of patients infected with human immunodeficiency virus (HIV), though the relevance of these findings to cognitive deterioration has not yet been determined. This study tested the hypothesis that diffusion tensor imaging can detect tissue status alterations in these regions in cognitively impaired patients infected with HIV and the acquired measurements correlate with the severity of cognitive impairment. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were determined for corpus callosum (genu and splenium) and frontal white matter (FWM). The DTI measurements were compared in 11 HIV and 11 control participants. Patterns of relationship were examined with cognitive status measures from concurrent neurologic and neuropsychologic evaluations. RESULTS: FA values for the splenium were significantly reduced in the patients infected with HIV and correlated with dementia severity and deficits in motor speed. MD values for the splenium were significantly increased in the patients infected with HIV and correlated with deficits in motor speed. FA measurements were also significantly correlated with performance on visual memory (genu), visuoconstruction (FWM), and verbal memory (FWM) tasks. CONCLUSION: Diffusion abnormalities were identified in the splenium of the corpus callosum in patients infected with HIV, and these alterations were associated with dementia severity and motor speed losses. In vivo assessment of callosal integrity by using quantitative neuroimaging may have potential utility as a marker of brain injury in patients infected with HIV.",Corpus Callosum/ pathology;Female;HIV Infections/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Wu, Y.;Storey, P.;Cohen, B. A.;Epstein, L. G.;Edelman, R. R.;Ragin, A. B.",2006,Mar,,0,
287,Impact of serum alkaline phosphatase on the cognitive impairment in patients with subcortical ischemic vascular disease,"Objective: To explore the levels of serum alkaline phosphatase (ALP) as well as its impact on the cognitive impairment in patients with subcortical ischemic vascular disease (SIVD). Methods: One hundred and fifty-eight SIVD patients were divided into two subgroups which included 86 patients with mild cognitive impairment (SVMCI) and 72 patients with vascular dementia (SVaD) according to the severity of cognitive impairment. Sixty-seven old people with normal cognitive function were selected as control qruop. Multiple lacunar infarction (LI) or leukoaraiosis (LA) was detected according to their MRI scan appearances and graded LA according to the severity. Serum ALP was measured by an enzymatic method as well as the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) were used in assessments. Serum ALP was divided into 3 groups and the occurrence rate of LI, LA and cognitive impairment were compared with each other. The levels of ALP were compared in different cognitive impairment and Logistic regression was used to explore the relation between ALP and cognitive impairment. Results: Both SVaD and SVMCI groups (17.00 (13.00, 20.00), 59.50 (49.00, 68.75); 25.00 (25.00, 26.00), 82.50 (76.75, 89.00)) showed significantly lower scores in MMSEand CAMCOG-C than control group (28.00 (28.00, 29.00), 93.00 (89.00, 96.00); Z=187.337, P=0.000; Z = 150.480, P = 0.000). A positive relationship between the elevated ALP level and the severity of cognitive impairment was found after adjusting for sex, age and other confunding factors ((68. 60±15.52), (78.76±13.39), (86.75 ± 18.85) U/L, F = 22.587, P = 0.000). The occurrence rate of LI, LA and SVaD among the three groups were significantly different (χ2= 8.008, P = 0.018; χ2 = 17. 998, P = 0.000; χ2 = 12.255, P = 0.002). The ALP level was negatively correlated with MMSE and CAMCOG-C scores (r = -0.350, P = 0.000; r = -0.286, P = 0.000). Logistic regression analysis revealed the relation between ALP and cognitive impairment was positive when we controlled all the vascular risk factors. However, the relation had gone when futher adjusting for the grade of LA. Conclusions: The level of ALP is significantly higher in SIVD patients and positively relates with cognitive impairment especially in those whose grade of LA is severe.",alkaline phosphatase;alkaline phosphatase blood level;article;Cambridge cognitive examination chinese version;cerebrovascular disease;clinical assessment tool;controlled study;disease severity;enzyme chemistry;female;human;lacunar stroke;leukoaraiosis;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;risk factor;subcortical ischemic vascular disease,"Wu, Y.;Shen, C.;Zhou, X.;Zhang, H.;You, M.;Zhu, X.;Sun, Z.",2016,,10.3760/cma.j.issn.1006-7876.2016.11.002,0,
288,Quantitative measurement to evaluate morphological changes of the corpus callosum in patients with subcortical ischemic vascular dementia,"Background: Subcortical ischemic vascular dementia (SIVD) is a subtype of dementia associated with abnormalities in the subcortical white matter regions. Recent imaging techniques can be used to detect such abnormalities in vivo. Purpose: To examine morphological changes of the corpus callosum in patients with SIVD by using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Material and Methods: MRI was performed to explore changes of cerebral white matter, especially corpus callosum. Brain matter diffusivity was examined with DTI by measuring the fractional anisotropy (FA). Results of 30 patients diagnosed with SIVD and 30 healthy subjects were analyzed and compared. Results: The thicknesses of the genu, the anterior third, middle, and posterior third of the body, and the splenium of the corpus callosum were smaller in SIVD patients compared to healthy controls (0.54±0.08 vs. 0.68±0.09 cm, P=0.0011; 0.27±0.06 vs. 0.38±0.07 cm, P=0.002; 0.28±0.05 vs. 0.38±0.08 cm, P=0.009; 0.18±0.04 vs. 0.26±0.06 cm, P=0.013; 0.54±0.07 vs. 0.72±0.09 cm, P=0.003, respectively). The FA values of the genu and splenium of the corpus callosum in patients with SIVD were decreased compared to healthy controls (0.664±0.042 vs. 0.778±0.041, P<0.001; 0.691±0.038 vs. 0.786±0.039, P=0.001, respectively). Conclusion: Patients with SIVD exhibit corpus callosum atrophy and morphological changes, and these characteristics may be useful for diagnosis.",,"Wu, X. P.;Gao, Y. J.;Yang, J. L.;Xu, M.;Sun, D. H.",2014,2014,,0,
289,Location of white matter changes and response to donepezil in patients with Alzheimer's disease: A retrospective and observational study,"AIM: The response to donepezil in patients with Alzheimer's disease varies, and it is important to identify the potential responder before therapy. Cerebral white matter changes (WMC) are frequently observed in older patients, and the effect of WMC on therapeutic response remains controversial. The present study aimed to investigate the relationships between the location of WMC, severe WMC and the response to donepezil. METHODS: Among 418 patients with Alzheimer's disease receiving donepezil, 196 patients were eligible for analysis. Five brain areas on each side were analyzed using computed tomography scans and the Age-Related White Matter Changes Rating Scale before therapy. The Cognitive Abilities Screening Instrument was used annually. Patients were defined as responders if their baseline Cognitive Abilities Screening Instrument score minus their follow-up Cognitive Abilities Screening Instrument score was </=0. RESULTS: There was no significant difference in demographic data between responder and non-responder groups. Patients in the responder group had significantly less involvement of WMC in the frontal area (P = 0.0213) and nearly a trend for less involvement of WMC in the basal ganglia (P = 0.1103). After adjustment for age, sex, education, polymorphism of apolipoprotein E, hypertension and diabetes, WMC in the frontal area (OR 0.446, P = 0.0139) and basal ganglia (OR 0.243, P = 0.0380) were significantly associated with a reduced therapeutic response. CONCLUSIONS: Patients with WMC in the frontal area and basal ganglia had significant decreases in their therapeutic response to donepezil. The location of WMC, independent of their severity, might be associated with the therapeutic response in patient with Alzheimer's disease. Geriatr Gerontol Int 2018; 18: 123-129.",Alzheimer's disease;cholinesterase inhibitors;donepezil;leukoaraiosis,"Wu, M. N.;Kao, Y. H.;Chou, P. S.;Lin, T. C.;Kao, L. L.;Yang, Y. H.",2018,Jan,,0,
290,Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease: Clinical correlations With Neurobehavioral Data in Cross-Sectional and After 18 Months Follow-ups,"Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to fiber tract integrity, we predefined 11 major association tracts and calculated tract specific fractional anisotropy (FA) values. Eighty-five patients with AD underwent neurobehavioral assessments including the minimental state examination (MMSE) and 12-item neuropsychiatric inventory twice with a 1.5-year interval to represent major outcome factors. In the cross-sectional data, total cholesterol, low-density lipoprotein, vitamin B12, and homocysteine levels correlated variably with WM FA values. After entering the biomarkers and WM FA into a regression model to predict neurobehavioral outcomes, only fiber tract FA or homocysteine level predicted the MMSE score, and fiber tract FA or age predicted the neuropsychiatric inventory total scores and subdomains of apathy, disinhibition, and aberrant motor behavior. In the follow-up neurobehavioral data, the mean global FA value predicted the MMSE and aberrant motor behavior subdomain, while age predicted the anxiety and elation subdomains. Cerebrovascular risk biomarkers may modify WM microstructural organization, while the association with fiber integrity showed greater clinical significance to the prediction of neurobehavioral outcomes both cross-sectionally and longitudinally.","Aged;Aged, 80 and over;Alzheimer Disease/blood/ pathology/psychology;Epidemiologic Studies;Female;Humans;Male;Regression Analysis;White Matter/ pathology","Wu, M. K.;Lu, Y. T.;Huang, C. W.;Lin, P. H.;Chen, N. C.;Lui, C. C.;Chang, W. N.;Lee, C. C.;Chang, Y. T.;Chen, S. F.;Chang, C. C.",2015,Jul,10.1097/md.0000000000001192,0,
291,A fully automated method for quantifying and localizing white matter hyperintensities on MR images,"White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P < 0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders. © 2006 Elsevier Ireland Ltd. All rights reserved.",,"Wu, M.;Rosano, C.;Butters, M.;Whyte, E.;Nable, M.;Crooks, R.;Meltzer, C. C.;Reynolds, I. C. F.;Aizenstein, H. J.",2006,1,,0,
292,Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease,"Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset (“premanifest” period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, “change-points”), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035–5050, 2017. © 2017 Wiley Periodicals, Inc.",adult;article;brain analysis;brain atrophy;brain mapping;brain region;brain size;CAG repeat;clinical assessment;controlled study;corpus striatum;cross-sectional study;diffusion tensor imaging;disease course;female;human;Huntington chorea;image segmentation;major clinical study;male;middle aged;multicenter study (topic);nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;treatment indication;white matter;white matter lesion,"Wu, D.;Faria, A. V.;Younes, L.;Mori, S.;Brown, T.;Johnson, H.;Paulsen, J. S.;Ross, C. A.;Miller, M. I.",2017,,10.1002/hbm.23713,0,
293,Brain structure and cognition in a community sample of elderly Latinos,"BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.","Aged;Aged, 80 and over;Aging/*physiology/*psychology;Analysis of Variance;Atrophy;Brain/*pathology;Chi-Square Distribution;Cognition Disorders/*diagnosis/epidemiology;Cohort Studies;Confidence Intervals;*Data Collection/methods/statistics & numerical data;Female;Hippocampus/pathology;Humans;Logistic Models;Magnetic Resonance Imaging;Male;*Mexican Americans/psychology/statistics & numerical data;Middle Aged;Odds Ratio","Wu, C. C.;Mungas, D.;Petkov, C. I.;Eberling, J. L.;Zrelak, P. A.;Buonocore, M. H.;Brunberg, J. A.;Haan, M. N.;Jagust, W. J.",2002,Aug 13,,0,
294,Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study,"BACKGROUND: Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. METHODS: A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. RESULTS: Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. CONCLUSIONS: These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage.",Aged;Brain/*pathology;Disease Progression;Female;Homocysteine/*blood;Humans;Hyperhomocysteinemia/complications;Magnetic Resonance Imaging;Male;Middle Aged;New York;Risk Factors;Social Class;Stroke/diagnosis;Vitamin B 12 Deficiency,"Wright, C. B.;Paik, M. C.;Brown, T. R.;Stabler, S. P.;Allen, R. H.;Sacco, R. L.;DeCarli, C.",2005,Jun,10.1161/01.str.0000165923.02318.22,0,
295,MRI Markers Predict Cognitive Decline Assessed by Telephone Interview: The Northern Manhattan Study,"Background: Brain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature. Methods: We examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white]. Results: Those in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3:-0.17 points/year, Q4:-0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1:-0.3 points/year, Q2:-0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV. Conclusions: Telephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.",antidiabetic agent;antihypertensive agent;antilipemic agent;apolipoprotein E4;adult;aged;allele;article;assessment of humans;Black person;brain;brain infarction;brain size;cerebral parenchymal fraction;cohort analysis;controlled study;diabetes mellitus;disease marker;female;Hispanic;human;hypercholesterolemia;hypertension;major clinical study;male;mental deterioration;modified Telephone Interview for Cognitive Status;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;prospective study;telephone interview;urban population;white matter;white matter hyperintensity volume;white matter lesion;1.5 T MRI system,"Wright, C. B.;Dong, C.;Caunca, M. R.;Derosa, J.;Kuen Cheng, Y.;Rundek, T.;Elkind, M. S. V.;DeCarli, C.;Sacco, R. L.",2017,,10.1097/wad.0000000000000158,0,
296,3-Methylglutaconic aciduria type i redefined: A syndrome with late-onset leukoencephalopathy,"Objective: 3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. It is thought to present in childhood with nonspecific symptoms; it was even speculated to be a nondisease. The natural course of disease is unknown. Methods: This is a study on 10 patients with 3-methylglutaconic aciduria type I. We present the clinical, neuroradiologic, biochemical, and genetic details on 2 new adult-onset patients and follow-up data on 2 patients from the literature. Results: Two unrelated patients with the characteristic biochemical findings of 3-methylglutaconic aciduria type I presented in adulthood with progressive ataxia. One patient additionally had optic atrophy, the other spasticity and dementia. Three novel mutations were found in conserved regions of the AUH gene. In both patients, MRI revealed extensive white matter disease. Follow-up MRI in a 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in deep white matter. Conclusion: We define 3-methylglutaconic aciduria type I as an inborn error of metabolism with slowly progressive leukoencephalopathy clinically presenting in adulthood. In contrast to the nonspecific findings in pediatric cases, the clinical and neuroradiologic pattern in adult patients is highly characteristic. White matter abnormalities may already develop in the first decades of life. The variable features found in affected children may be coincidental. Long-term follow-up in children is essential to learn more about the natural course of this presumably slowly progressive disease. Dietary treatment with leucine restriction may be considered. Copyright © 2010 by AAN Enterprises, Inc. All rights reserved.",3 hydroxyisovaleric acid;3 methylglutaconic acid;3 methylglutaric acid;AUH protein;isovaleric acid;protein;unclassified drug;3 methylglutaconic aciduria type 1;aciduria;adult;article;ataxia;attention deficit disorder;cerebellar ataxia;cerebrospinal fluid analysis;child;clinical article;consanguinity;dementia;disease course;dysarthria;febrile convulsion;female;Fibrobacter;follow up;gene deletion;homozygosity;human;inborn error of metabolism;infant;leukoencephalopathy;male;mental retardation malformation syndrome;motor dysfunction;mutational analysis;Netherlands;neuroradiology;newborn screening;nuclear magnetic resonance imaging;optic nerve atrophy;priority journal;proton nuclear magnetic resonance;school child;spastic paraplegia;spasticity;speech discrimination;United Kingdom;urinalysis;visual impairment;white matter,"Wortmann, S. B.;Kremer, B. H.;Graham, A.;Willemsen, M. A.;Loupatty, F. J.;Hogg, S. L.;Engelke, U. F.;Kluijtmans, L. A.;Wanders, R. J.;Illsinger, S.;Wilcken, B.;Cruysberg, J. R.;Das, A. M.;Morava, E.;Wevers, R. A.",2010,,,0,
297,Leukoencephalopathy in a patient taking low dose oral methotrexate therapy for rheumatoid arthritis,"We describe the case of a man who developed a dementing illness with leukoencephalopathy while receiving low dose weekly oral methotrexate (MTX) therapy for rheumatoid arthritis. The white matter changes seen on magnetic resonance imaging and computerized tomogram scan were the same as those seen in cases of leukoencephalopathy that have been reported in patients receiving intravenous or intrathecal methotrexate. Extensive investigation excluded other known causes of white matter disease. Although no improvement either subjectively or objectively occurred in his mental status after cessation of treatment with MTX, he has remained stable. We believe that this may represent a case of oral MTX induced leukoencephalopathy, which has not previously been reported.",,"Worthley, S. G.;McNeil, J. D.",1995,1995,,0,
298,"Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: A tract-based spatial statistics study","Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD.",,"Worker, A.;Blain, C.;Jarosz, J.;Chaudhuri, K. R.;Barker, G. J.;Williams, S. C. R.;Brown, R. G.;Leigh, P. N.;Dell'acqua, F.;Simmons, A.",2014,,,0,
299,Neurological deterioration in late infantile neuronal ceroid lipofuscinosis,"BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL) is associated with progressive degeneration of the brain and retina starting in early childhood. METHODS: Thirty-two individual neurologic, ophthalmologic, and CNS imaging (MRI and MRS) assessments of 18 children with LINCL were analyzed. Disease severity was followed by two rating scales, one previously established but modified to solely assess the brain and exclude the retinal disease (modified Hamburg LINCL scale), and a newly developed scale, with expanded evaluation of the CNS impairment (Weill Cornell LINCL scale). RESULTS: For the 18 children, the Weill Cornell scale yielded a closer correlation with both age and time since initial clinical manifestation of the disease than did the modified Hamburg scale. There were no significant differences as a function of age or time since initial manifestation of the disease in the rating scales among the most frequent CLN2 mutations (G3556C, 56% of all alleles or C3670T, 22% of all alleles). Measurements of cortical MRS N-acetyl-aspartate content, MRI ventricular, gray matter and white matter volume, and cortical apparent diffusion coefficient correlated to a variable degree with the age of the children and the time since initial clinical manifestation of the disease. All imaging measurements correlated better with the Weill Cornell CNS scale compared to the modified Hamburg LINCL scale. CONCLUSION: The data suggest that the Weill Cornell late infantile neuronal ceroid lipofuscinosis (LINCL) scale, together with several of the MRI measurements, may be useful in the assessment of severity and progression of LINCL and for the evaluation of novel therapeutic strategies. ©2007AAN Enterprises, Inc.",,"Worgall, S.;Kekatpure, M. V.;Heier, L.;Ballon, D.;Dyke, J. P.;Shungu, D.;Mao, X.;Kosofsky, B.;Kaplitt, M. G.;Souweidane, M. M.;Sondhi, D.;Hackett, N. R.;Hollmann, C.;Crystal, R. G.",2007,August,,0,
300,Olfactory identification deficit predicts white matter tract impairment in Alzheimer's disease,"Olfactory identification deficit (OID) has been associated with both aging and Alzheimer's disease (AD). In the context of an amnestic disorders, OID predicts conversion to AD. Neuroanatomical correlates could increase specificity and sensitivity and elucidate the mechanistic differences between OID in AD and aging. Cross-sectional analysis of white matter microstructural changes was performed using diffusion tensor imaging (DTI) and tract-based-spatial-statistics in amnestic mild cognitive impairment (aMCI), AD and normal controls (NC) in 66 subjects (26 AD, 15 aMCI, 25 NC). DTI 3-Tesla MRI scans were analyzed and subject level means for fractional anisotropy (FA), mean diffusivity (MD), radial and axial diffusivity (lambda1D and lambda2,3D) were calculated. Linear regression models were applied using DTI markers as predictor and OID as outcome. OID was associated with increased lambda1D in aMCI and increased MD, lambda1D and lambda2,3D in AD. Voxel-wise analyses revealed widespread differences in all markers in AD. There were significant differences in lambda1D in aMCI, particularly in the olfactory tract. OID is correlated with microstructural white matter changes as early as in aMCI. This study may help elucidate the biological basis for olfactory impairment in Alzheimer's disease. Neuroanatomical correlates could help distinguish OID associated with AD and that associated with aging.",Alzheimer's disease;Amnestic mild cognitive impairment;Diffusion tensor imaging;Mri;Olfactory;White Matter,"Woodward, M. R.;Dwyer, M. G.;Bergsland, N.;Hagemeier, J.;Zivadinov, R.;Benedict, R. H.;Szigeti, K.",2017,Aug 30,,0,
301,"Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer's disease subjects","OBJECTIVE: We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to increase our understanding of the role of brain lipids in pathophysiology of aging and age-related cognitive impairment. METHODS: Levels of 650 individual lipids, across 26 lipid subclasses, were measured utilising a high-resolution mass spectrometric analysis platform. RESULTS: Monoacylglycerols (MAG), diacylglycerols (DAG), and the very-long-chain fatty acid 26:0 were elevated in the grey matter of the mild cognitive impairment (MCI) and old dementia (OD) cohorts. Ethanolamine plasmalogens (PlsEtn) were decreased in the grey matter of the young dementia (YD) and OD cohorts while and phosphatidylethanolamines (PtdEth) were lower in the MCI, YD and OD cohorts. In the white matter, decrements in sulphatide levels were detected in the YD group, DAG levels were elevated in the MCI group, and MAG levels were increased in the YD and OD groups. CONCLUSION: The parallel changes in grey matter MAGs and DAGs in the MCI and OD groups suggest that these two cohorts may have a similar underlying pathophysiology; consistent with this, MCI subjects were more similar in age to OD than to YD subjects. While PlsEtn and phosphatidylethanolamine were decreased in the YD and OD groups they were unaltered in the MCI group indicating that alterations in plasmalogen synthesis are unlikely to represent an initiating event in the transition from MCI to dementia.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/*metabolism/pathology;Biomarkers/cerebrospinal fluid/metabolism;Brain/*metabolism;Dementia/*metabolism/pathology;Diagnosis;Diglycerides/cerebrospinal fluid/*metabolism;Docosahexaenoic Acids/cerebrospinal fluid/metabolism;Female;Frontal Lobe/metabolism;Humans;Magnetic Resonance Imaging/methods;Male;Mild Cognitive Impairment/cerebrospinal fluid/*metabolism/pathology;Monoglycerides/cerebrospinal fluid/*metabolism;Neuropsychological Tests;Plasmalogens/cerebrospinal fluid/*metabolism;White Matter/metabolism;Alzheimer's disease;diacylglycerols;frontal cortex;lipidomics;mild cognitive impairment","Wood, P. L.;Barnette, B. L.;Kaye, J. A.;Quinn, J. F.;Woltjer, R. L.",2015,Oct,10.1017/neu.2015.18,0,
302,Mitochondrial syndromes with leukoencephalopathies,"White matter involvement has recently been recognized as a common feature in patients with multisystem mitochondrial disorders that may be caused by molecular defects in either the mitochondrial genome or the nuclear genes. It was first realized in classical mitochondrial syndromes associated with mitochondrial DNA (mtDNA) mutations, such as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Leigh's disease, and Kearns-Sayre's syndrome. Deficiencies in respiratory chain complexes I, II, IV, and V often cause Leigh's disease; most of them are due to nuclear defects that may lead to severe early-onset leukoencephalopathies. Defects in a group of nuclear genes involved in the maintenance of mtDNA integrity may also affect the white matter; for example, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) caused by thymidine phosphorylase deficiency, Navajo neurohepatopathy (NNH) due to MPV17 mutations, and Alpers syndrome due to defects in DNA polymerase gamma (POLG). More recently, leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) has been reported to be caused by autosomal recessive mutations in a mitochondrial aspartyl-tRNA synthetase, DARS2 gene. A patient with leukoencephalopathy and neurologic complications in addition to a multisystem involvement warrants a complete evaluation for mitochondrial disorders. A definite diagnosis may be achieved by molecular analysis of candidate genes based on the biochemical, clinical, and imaging results. © 2012 by Thieme Medical Publishers, Inc.",,"Wong, L. J. C.",2012,2012,,0,
303,In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir corrected F 18),"An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methy l benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18). METHODS: An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects. RESULTS: Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed. CONCLUSION: (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.",Aged;Alzheimer Disease/ metabolism/ radionuclide imaging;Amyloid/ metabolism;Aniline Compounds/adverse effects/pharmacokinetics;Brain/metabolism/radionuclide imaging;Case-Control Studies;Drug-Related Side Effects and Adverse Reactions;Ethylene Glycols/adverse effects/pharmacokinetics;Female;Fluorine Radioisotopes;Humans;Male;Positron-Emission Tomography;Radiometry;Whole-Body Irradiation,"Wong, D. F.;Rosenberg, P. B.;Zhou, Y.;Kumar, A.;Raymont, V.;Ravert, H. T.;Dannals, R. F.;Nandi, A.;Brasic, J. R.;Ye, W.;Hilton, J.;Lyketsos, C.;Kung, H. F.;Joshi, A. D.;Skovronsky, D. M.;Pontecorvo, M. J.",2010,Jun,10.2967/jnumed.109.069088,0,
304,Comparing Mattis Dementia Rating Scale--initiation/perseveration subset and frontal assessment battery in stroke associated with small vessel disease,"Forty-two controls and 32 patients with stroke associated with small vessel disease (SSVD) were administered the Mattis Dementia Rating Scale Initiation / Perseveration subset (MDRS I/P) and Frontal Assessment Battery (FAB). Both tests showed comparably good ability in Receiver Operating Characteristics curves analysis (AUCMDRS I/P=0.887; AUC FAB=0.854, p=.833) in discriminating between controls and patients and correctly classified over 78% of subjects. Verbal fluency and motor programming contributed most to the discriminating power in the two tests. The MDRS I/P and FAB are useful in discriminating between controls and SSVD patients in a hospital setting.","Aged;Area Under Curve;Cerebral Infarction/pathology/psychology;Cerebrovascular Disorders/complications/pathology/*psychology;Dementia/pathology/*psychology;Diagnosis, Differential;Female;Frontal Lobe/pathology/physiopathology;Humans;Interview, Psychological;Magnetic Resonance Imaging;Male;Multivariate Analysis;*Neuropsychological Tests;Psychometrics;ROC Curve;Reference Values;Regression Analysis;Stroke/etiology/pathology/*psychology;Verbal Behavior/physiology","Wong, A.;Mok, V. C.;Tang, W. K.;Lam, W. W.;Wong, K. S.",2007,Feb,10.1080/13803390600582453,0,
305,Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease,"BACKGROUND: Hyperhomocysteinemia is associated with cerebral small vessel disease (SVD). We examined the relationship between homocysteine and 1) volumetric measure of white matter change (WMC), 2) silent brain infarcts, 3) cerebral atrophy on MRI and 4) cognition on a consecutive cohort of patients with stroke associated with SVD. SUBJECTS AND METHODS: Fifty-seven patients consecutively admitted to the Acute Stroke Unit in a university hospital due to stroke associated with SVD were recruited and assessed three months after the stroke. Non-fasting homocysteine was obtained. Using MRI, the number of infarcts, volume of WMC and cerebral atrophy were measured. General cognitive functions were assessed using the Mini Mental State Examination and Alzheimer's disease Assessment Scale. Mattis Dementia Rating Scale - Initiation/Perseveration subset was used to assess executive cognitive functions. RESULTS: Hyperhomocysteinemia (> or = 14.88 micromol/L) significantly accounted for the volume of WMC on MRI in a multivariate stepwise regression model (adjusted R(2)=0.058, p <0.05) after adjustment for age and folate level. Patients in the highest quartile of WMC volume had significantly higher levels of homocysteine than those in lowest quartile (p <0.001). No significant relationship was found between homocysteine and silent brain infarcts, cerebral atrophy and performance on psychometric tests. CONCLUSION: Hyperhomocysteinemia is associated with volumetric measure of WMC among patients with SVD. The role of homocysteine in the development of silent brain infarcts and cerebral atrophy as previously reported cannot be ascertained in this study. No direct relationship was found between homocysteine and cognitive functions.",Aged;Brain/*pathology;Cerebrovascular Disorders/blood/*pathology/psychology;Cognition Disorders/etiology;Cohort Studies;Creatinine/blood;Female;Homocysteine/blood;Humans;Hyperhomocysteinemia/blood/*pathology/psychology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Psychometrics;Regression Analysis;Risk Factors;Stroke/etiology/pathology;Vitamin B 12/blood,"Wong, A.;Mok, V.;Fan, Y. H.;Lam, W. W.;Liang, K. S.;Wong, K. S.",2006,Apr,10.1007/s00415-005-0022-x,0,
306,Cerebral Perfusion and the Risk of Dementia: A Population-Based Study,"BACKGROUND: Cerebral hypoperfusion has previously been associated with mild cognitive impairment and dementia in various cross-sectional studies, but whether hypoperfusion precedes neurodegeneration is unknown. We prospectively determined the association of cerebral perfusion with subsequent cognitive decline and development of dementia. METHODS: Between 2005 and 2012, we measured cerebral blood flow by 2-dimensional phase-contrast magnetic resonance imaging in participants of the population-based Rotterdam Study without dementia. We determined the association of cerebral perfusion (mL/100mL/min) with risk of dementia (until 2015) using a Cox model, adjusting for age, sex, demographics, cardiovascular risk factors, and apolipoprotein E genotype. We repeated analyses for Alzheimer disease and accounting for stroke. We used linear regression to determine change in cognitive performance during 2 consecutive examination rounds in relation to perfusion. Finally, we investigated whether associations were modified by baseline severity of white matter hyperintensities. RESULTS: Of 4759 participants (median age 61.3 years, 55.2% women) with a median follow-up of 6.9 years, 123 participants developed dementia (97 Alzheimer disease). Lower cerebral perfusion was associated with higher risk of dementia (adjusted hazard ratio, 1.31; 95% confidence interval per standard deviation decrease, 1.07-1.61), similar for Alzheimer disease only, and unaltered by accounting for stroke. Risk of dementia with hypoperfusion was higher with increasing severity of white matter hyperintensities (with severe white matter hyperintensities; hazard ratio, 1.54; 95% confidence interval, 1.11-2.14). At cognitive reexamination after on average 5.7 years, lower baseline perfusion was associated with accelerated decline in cognition (global cognition: beta=-0.029, P=0.003), which was similar after excluding those with incident dementia, and again most profound in individuals with higher volume of white matter hyperintensities (P value for interaction=0.019). CONCLUSIONS: Cerebral hypoperfusion is associated with accelerated cognitive decline and an increased risk of dementia in the general population.","Aged;Aged, 80 and over;Cerebrovascular Circulation/ physiology;Cohort Studies;Dementia/ diagnostic imaging/ epidemiology/physiopathology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Netherlands/epidemiology;Population Surveillance/methods;Prospective Studies;Risk Factors;White Matter/ blood supply/ diagnostic imaging/physiopathology;Alzheimer disease;cerebral blood flow;cerebral perfusion;dementia;epidemiology;small-vessel disease","Wolters, F. J.;Zonneveld, H. I.;Hofman, A.;van der Lugt, A.;Koudstaal, P. J.;Vernooij, M. W.;Ikram, M. A.;Heart-Brain Connection Collaborative Research, Group",2017,Aug 22,,0,
307,Parental family history of dementia in relation to subclinical brain disease and dementia risk,"OBJECTIVE: To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort. METHODS: From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI. RESULTS: Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61-4.15; >/=80 years: HR 1.01, 95% CI 0.58-1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history. CONCLUSIONS: Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.",0 (Apolipoproteins E);Age of Onset;Aged;Apolipoproteins E/genetics;Brain/diagnostic imaging;Cardiovascular Diseases/epidemiology;Cohort Studies;Dementia/diagnostic imaging/ epidemiology/genetics;F Factor;Female;Follow-Up Studies;Genetic Predisposition to Disease;Genotyping Techniques;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Parents;Risk Factors,"Wolters, F. J.;van der Lee, S. J.;Koudstaal, P. J.;van Duijn, C. M.;Hofman, A.;Ikram, M. K.;Vernooij, M. W.;Ikram, M. A.",2017,Apr 25,,0,308
308,Parental family history of dementia in relation to subclinical brain disease and dementia risk,"OBJECTIVE: To determine the association of parental family history with risk of dementia by age at onset and sex of affected parent in a population-based cohort. METHODS: From 2000 to 2002, we assessed parental history of dementia in participants without dementia of the Rotterdam Study. We investigated associations of parental history with risk of dementia until 2015, adjusting for demographics, cardiovascular risk factors, and known genetic risk variants. Furthermore, we determined the association between parental history and markers of neurodegeneration and vascular disease on MRI. RESULTS: Of 2,087 participants (mean age 64 years, 55% female), 407 (19.6%) reported a history of dementia in either parent (mean age at diagnosis 79 years). During a mean follow-up of 12.2 years, 142 participants developed dementia. Parental history was associated with risk of dementia independently of known genetic risk factors (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48), in particular when parents were diagnosed at younger age (<80 years: HR 2.58, 95% CI 1.61-4.15; >/=80 years: HR 1.01, 95% CI 0.58-1.77). Accordingly, age at diagnosis in probands was highly correlated with age at diagnosis in their parents <80 years (r = 0.57, p = 0.001) but not thereafter (r = 0.17, p = 0.55). Among 1,161 participants without dementia with brain MRI, parental history was related to lower cerebral perfusion and higher burden of white matter lesions and microbleeds. Dementia risk and MRI markers were similar for paternal and maternal history. CONCLUSIONS: Parental history of dementia increases risk of dementia, primarily when age at parental diagnosis is <80 years. Unexplained heredity may be attributed in part to cerebral hypoperfusion and small vessel disease. We found no evidence of preferential maternal compared to paternal transmission.",,"Wolters, F. J.;van der Lee, S. J.;Koudstaal, P. J.;van Duijn, C. M.;Hofman, A.;Ikram, M. K.;Vernooij, M. W.;Ikram, M. A.",2017,Mar 29,,0,
309,The Determinants of Dementia After Stroke (DEDEMAS) Study: protocol and pilot data,"RATIONALE: About 20% of stroke patients develop dementia within a few months after their event, but the determinants and mechanisms of poststroke dementia are insufficiently understood. AIMS: To identify and characterize the determinants of cognitive impairment poststroke. DESIGN: Observational prospective study in patients with acute stroke and no prior dementia. Six hundred subjects will be characterized by detailed interview, standardized clinical examinations, biometric measures (intima-media thickness, waist-hip ratio, and ankle-brachial index), multimodal imaging (magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid-positron emission tomography (amyloid-PET), and retinal imaging), analysis of biomarkers derived from blood and cerebrospinal fluid, and detailed cognitive testing at repeat time points. Patients will be followed for five-years with a total of five personal visits and three telephone interviews. STUDY OUTCOMES: Primary end-point is the occurrence of poststroke dementia. Secondary end-points include poststroke cognitive impairment-no dementia, stroke recurrence, and death. Predictive factors for poststroke dementia will be identified by multiple Cox proportional-hazards model. RESULTS: Baseline characteristics of the first 71 patients (study inclusion between May 2011 and August 2012) are as follows: median age, 70 years (interquartile range, 65-75); female gender, 25 (35%); median National Institutes of Health Stroke Scale at admission, 2 (1-4); and etiological stroke subtypes according to TOAST classification, 15% large artery disease, 18% small vessel disease, 35% cardioembolic, and 32% undetermined or multiple competing etiologies. DISCUSSION: This study will provide insights into the mechanisms of poststroke dementia and hold the potential to identify novel diagnostic markers and targets for preventive therapies. The study is registered at http://www.clinicaltrials.gov (NCT01334749) and will be extended as a multicenter study starting 2013.",Aged;Amyloid/metabolism;Ankle Brachial Index;Carotid Intima-Media Thickness;Cohort Studies;Dementia/ diagnosis/ etiology/therapy;Female;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging;Male;Neurologic Examination;Neuropsychological Tests;Pilot Projects;Positron-Emission Tomography;Retina/pathology;Stroke/ complications;Treatment Outcome;Waist-Hip Ratio,"Wollenweber, F. A.;Zietemann, V.;Rominger, A.;Opherk, C.;Bayer-Karpinska, A.;Gschwendtner, A.;Coloma Andrews, L.;Burger, K.;Duering, M.;Dichgans, M.",2014,Apr,10.1111/ijs.12092,0,
310,Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in vitro,"Background and Purpose-Mutations in NOTCH3 cause cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated. Methods-We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay. Results-We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL. Conclusions-Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance.",cysteine;Notch3 receptor;adult;aged;amino acid substitution;amnesia;article;CADASIL;clinical article;clinical examination;consciousness disorder;controlled study;executive function;exon;female;gait apraxia;gene mutation;gene sequence;genetic screening;genetic variability;hemiparesis;human;human tissue;in vitro study;major depression;male;medical history;migraine;mutant;neuroimaging;neuropsychology;nuclear magnetic resonance imaging;phenotype;presyncope;priority journal;protein aggregation;psychosomatic disorder;quadriplegia;sibling;single nucleotide polymorphism;skin biopsy;structured interview;ultrastructure,"Wollenweber, F. A.;Hanecker, P.;Bayer-Karpinska, A.;Malik, R.;Bäzner, H.;Moreton, F.;Muir, K. W.;Müller, S.;Giese, A.;Opherk, C.;Dichgans, M.;Haffner, C.;Duering, M.",2015,,10.1161/strokeaha.114.007472,0,311
311,Cysteine-Sparing CADASIL Mutations in NOTCH3 Show Proaggregatory Properties In Vitro,"BACKGROUND AND PURPOSE—: Mutations in NOTCH3 cause cerebral autosomal–dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common monogenic cause of stroke and vascular dementia. Misfolding and aggregation of NOTCH3 proteins triggered by cysteine-affecting mutations are considered to be the key disease mechanisms. However, the significance of cysteine-sparing mutations is still debated.METHODS—: We studied a family with inherited small vessel disease by standardized medical history, clinical examination, MRI, ultrastructural analysis of skin biopsies, and Sanger sequencing of all NOTCH3 exons. In addition, we performed in vitro characterization of NOTCH3 variants using recombinant protein fragments and a single-particle aggregation assay.RESULTS—: We identified a novel cysteine-sparing NOTCH3 mutation (D80G) in 4 family members, which was absent in a healthy sibling. All mutation carriers exhibited a CADASIL typical brain imaging and clinical phenotype, whereas skin biopsy showed inconsistent results. In vitro aggregation behavior of the D80G mutant was similar compared with cysteine-affecting mutations. This was reproduced with cysteine-sparing mutations from previously reported families having a phenotype consistent with CADASIL.CONCLUSIONS—: Our findings support the view that cysteine-sparing mutations, such as D80G, might cause CADASIL with a phenotype largely indistinguishable from cysteine mutations. The in vitro aggregation analysis of atypical NOTCH3 mutations offers novel insights into pathomechanisms and might represent a tool for estimating their clinical significance.",,"Wollenweber, F. A.;Hanecker, P.;Bayer-Karpinska, A.;Malik, R.;Bäzner, H.;Moreton, F.;Muir, K. W.;Müller, S.;Giese, A.;Opherk, C.;Dichgans, M.;Haffner, C.;Duering, M.",2015,,,0,
312,Prevalence of cortical superficial siderosis in patients with cognitive impairment,"Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group.","Aged;Cardiovascular Diseases/complications;Cerebral Amyloid Angiopathy/pathology;Cerebral Hemorrhage/etiology/pathology;Cognition Disorders/complications/ epidemiology/psychology;Dementia/etiology;Female;Humans;Image Processing, Computer-Assisted;International Classification of Diseases;Magnetic Resonance Imaging;Male;Neuroimaging;Neuropsychological Tests;Prevalence;Risk Assessment;Risk Factors;Siderosis/complications/ epidemiology/psychology","Wollenweber, F. A.;Buerger, K.;Mueller, C.;Ertl-Wagner, B.;Malik, R.;Dichgans, M.;Linn, J.;Opherk, C.",2014,Feb,10.1007/s00415-013-7181-y,0,
313,Cortical Superficial Siderosis in Different Types of Cerebral Small Vessel Disease,"Background and Purpose - Cortical superficial siderosis (cSS) has emerged as a clinically relevant imaging feature of cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is also present in nonamyloid-associated small vessel disease and whether patients with cSS differ in terms of other small vessel disease imaging features. Methods - Three hundred sixty-four CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) patients, 372 population-based controls, and 100 CAA patients with cSS (fulfilling the modified Boston criteria for possible/probable CAA) were included. cSS and cerebral microbleeds were visually rated on T2∗-weighted magnetic resonance imaging. White matter hyperintensities were segmented on fluid-attenauted inversion recovery images, and their spatial distribution was compared between groups using colocalization analysis. Cerebral microbleeds location was determined in an observer-independent way using an atlas in standard space. Results - cSS was absent in CADASIL and present in only 2 population-based controls (0.5%). Cerebral microbleeds were present in 64% of CAA patients with cSS, 34% of patients with CADASIL, and 12% of population-based controls. Among patients with cerebral microbleeds, lobar location was found in 95% of CAA patients with cSS, 48% of CADASIL patients, and 69% of population-based controls. The spatial distribution of white matter hyperintensities was comparable between CAA with cSS and CADASIL as indicated by high colocalization coefficients. Conclusions - cSS was absent in CADASIL, whereas other small vessel disease imaging features were similar to CAA patients with cSS. Our findings suggest that cSS in combination with other small vessel disease imaging markers is highly indicative of CAA.",adult;article;brain hemorrhage;CADASIL;cerebrovascular disease;controlled study;cortical superficial siderosis;female;human;image analysis;major clinical study;male;neuroimaging;nuclear magnetic resonance imaging;priority journal;prospective study;siderosis;vascular amyloidosis;white matter lesion,"Wollenweber, F. A.;Baykara, E.;Zedde, M.;Gesierich, B.;Achmüller, M.;Jouvent, E.;Viswanathan, A.;Ropele, S.;Chabriat, H.;Schmidt, R.;Opherk, C.;Dichgans, M.;Linn, J.;Duering, M.",2017,,10.1161/strokeaha.117.016833,0,
314,Classification of cardiogenic stroke - overcoming the challenges,"Precise analysis of stroke subtypes is important for clinical treatment decisions and prognostic evaluation of patients leading to adapted individual patient management. Cardiogenic stroke represents a major part with approximately one-third of all ischaemic strokes, but evaluation is not as simple as could be expected. This is reflected by new classification systems like the Atherosclerosis, Small Vessel Disease, Cardiac Origin and Other Causes (ASCO) score, which permits a more comprehensive evaluation of people who have had a stroke. They allow better presentation of concomitant stroke aetiologies that influence primary management and secondary prophylaxis in cardiogenic stroke patients. Careful analysis of different ischaemic stroke patterns as well as demonstration of either symptomatic or asymptomatic previous ischaemic stroke and/or intracerebral bleedings on magnetic resonance imaging (MRI) is essential for adequate interpretation and best individual choice of antiplatelet/anticoagulation treatment. As a consequence, all people who have had a stroke should undergo a complete stroke work-up, even if a cardioembolic source like atrial fibrillation might be easily detected initially. Future aspects will address the increasing numbers of old people with both neurodegenerative, vascular and cardiac diseases with mutual interference of treatment and prevention regimens. © TOUCH BRIEFINGS 2011.",,"Wolf, M. E.;Henneric, M. G.",,2012,,0,
315,Structural correlates of mild cognitive impairment,"The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.","Aged;Aged, 80 and over;Anthropometry;Atrophy;Brain/anatomy & histology/pathology;Cognition Disorders/ diagnosis/physiopathology;Cross-Sectional Studies;Dementia/ diagnosis;Female;Hippocampus/anatomy & histology/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Matched-Pair Analysis;Neuropsychological Tests;Regression Analysis;Severity of Illness Index","Wolf, H.;Hensel, A.;Kruggel, F.;Riedel-Heller, S. G.;Arendt, T.;Wahlund, L. O.;Gertz, H. J.",2004,Aug,,0,316
316,Structural correlates of mild cognitive impairment,"The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.","Anthropometry;Atrophy;Brain [anatomy & histology] [pathology];Cognition Disorders [diagnosis] [physiopathology];Cross-Sectional Studies;Dementia [diagnosis];Hippocampus [anatomy & histology] [pathology];Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Matched-Pair Analysis;Neuropsychological Tests;Regression Analysis;Severity of Illness Index;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Wolf, H.;Hensel, A.;Kruggel, F.;Riedel-Heller, S. G.;Arendt, T.;Wahlund, L. O.;Gertz, H. J.",2004,,10.1016/j.neurobiolaging.2003.08.006,0,
317,Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study,"OBJECTIVE: White matter lesions on brain CT or MRI are a frequent finding in patients with Alzheimer's disease. However, little is known about the prognostic significance of these changes in cognitively impaired individuals who are at risk for subsequent development of dementia. This study aims at investigating the potential impact of white matter lucencies (WML) on brain CT on the course of mild cognitive impairment. PATIENTS AND METHODS: Twenty-seven patients (mean age 72, SD 4.03) with mild cognitive impairment (MCI) and no signs of cerebrovascular disease were prospectively examined. At their initial presentation, all patients underwent a structured interview for the diagnosis of dementia (SIDAM) and a brain CT. Linear measures of atrophy and visual ratings of white matter changes were performed. At follow-up (mean interval 29 months), these patients were re-examined with the SIDAM. Eight patients had developed dementia and met clinical criteria for Alzheimer's disease (crossover group). RESULTS: Evaluation of the initial CT scans revealed significantly more frequent and extended white matter abnormalities and a higher degree of temporal lobe atrophy in the crossover group as compared to the cognitively stable group. In the crossover group, high WML severity initially was associated with a lesser degree of temporal lobe atrophy and higher global cognitive performance. CONCLUSION: We conclude that WML play a role in the dementia process and that they might accelerate cognitive decline in individuals with mild cognitive impairment. WML should be included in prospective studies of MCI as potential predictor variables.","Aged;Aged, 80 and over;Cognition Disorders/*etiology;Dementia/*etiology;Female;Humans;Longitudinal Studies;Male;Temporal Lobe/*pathology;Tomography, X-Ray Computed","Wolf, H.;Ecke, G. M.;Bettin, S.;Dietrich, J.;Gertz, H. J.",2000,Sep,,0,
318,Association of basal forebrain volumes and cognition in normal aging,"The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.","Aged;Aged, 80 and over;*Aging;Attention;*Cognition;Cohort Studies;Educational Status;Executive Function;Female;Humans;Intelligence;Intelligence Tests;Linear Models;Magnetic Resonance Imaging;Male;Memory;Middle Aged;Neuropsychological Tests;Organ Size;Telencephalon/*anatomy & histology;Basal forebrain cholinergic system;Brain resilience;Cognition;General intelligence;Normal aging;Nucleus basalis of Meynert","Wolf, D.;Grothe, M.;Fischer, F. U.;Heinsen, H.;Kilimann, I.;Teipel, S.;Fellgiebel, A.",2014,Jan,10.1016/j.neuropsychologia.2013.11.002,0,
319,Non-Linear Association between Cerebral Amyloid Deposition and White Matter Microstructure in Cognitively Healthy Older Adults,"Cerebral amyloid-beta accumulation and changes in white matter (WM) microstructure are imaging characteristics in clinical Alzheimer's disease and have also been reported in cognitively healthy older adults. However, the relationship between amyloid deposition and WM microstructure is not well understood. Here, we investigated the impact of quantitative cerebral amyloid load on WM microstructure in a group of cognitively healthy older adults. AV45-positron emission tomography and diffusion tensor imaging (DTI) scans of forty-four participants (age-range: 60 to 89 years) from the Alzheimer's Disease Neuroimaging Initiative were analyzed. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR), and axial diffusivity (DA) were calculated to characterize WM microstructure. Regression analyses demonstrated non-linear (quadratic) relationships between amyloid deposition and FA, MD, as well as RD in widespread WM regions. At low amyloid burden, higher deposition was associated with increased FA as well as decreased MD and DR. At higher amyloid burden, higher deposition was associated with decreased FA as well as increased MD and DR. Additional regression analyses demonstrated an interaction effect between amyloid load and global WM FA, MD, DR, and DA on cognition, suggesting that cognition is only affected when amyloid is increasing and WM integrity is decreasing. Thus, increases in FA and decreases in MD and RD with increasing amyloid load at low levels of amyloid burden may indicate compensatory processes that preserve cognitive functioning. Potential mechanisms underlying the observed non-linear association between amyloid deposition and DTI metrics of WM microstructure are discussed.",,"Wolf, D.;Fischer, F. U.;Scheurich, A.;Fellgiebel, A.",2015,,10.3233/jad-150049,0,
320,Hippocampal disconnection in early Alzheimer's disease: A 7 tesla MRI study,"Background: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. Objective: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD. Methods: Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume. Results: Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus &CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (β = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes. Conclusion: These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD.",adult;Alzheimer disease;article;brain fornix;brain size;cingulum (brain);clinical article;controlled study;dentate gyrus;dentate hilus;diffusion weighted imaging;entorhinal cortex;female;fractional anisotropy;hippocampal CA1 region;human;investigative procedures;male;mild cognitive impairment;nuclear magnetic resonance imaging;parahippocampal cingulum;priority journal;subiculum,"Wisse, L. E. M.;Reijmer, Y. D.;Ter Telgte, A.;Kuijf, H. J.;Leemans, A.;Luijten, P. R.;Koek, H. L.;Geerlings, M. I.;Biessels, G. J.;Van Den Berg, E.;Brundel, M.;Bouvy, W. H.;Heringa, S. M.;Kappelle, L. J.;De Bresser, J.;Mali, W. P. Th M.;Viergever, M. A.;Vincken, K. L.;Zwanenburg, J. J. M.;De Wit, J. E.;Hamaker, M.;Faaij, R.;Pleizier, M.;Vriens, E.;Algra, A.;Van Der Graaf, Y.;Rutten, G. E. H. M.",2015,,,0,
321,New subform of the late infantile form of neuronal ceroid lipofuscinosis,"Clinicopathological studies of a series of nine children with a new subform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is between 2.5-3.5 years of age with initial neurological symptoms of abnormal motor skills caused by cerebellar and extrapyramidal signs. Soon after dementia, myoclonic seizures are followed. Visual impairment is more clearly seen after the age of 5 or 6 years. The ultrastructural studies of the skin and/or buffy coat showed abundant lysosomal storage of curvilinear profiles, rarely intermixed with fingerprint profiles. The MRI of the head performed in seven cases, showed initially enlargement of the ventricles that is secondary to basal ganglia atrophy and presence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased signals of T2-weighted imaging in the periventricular areas of the fronto-parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). The MRI in Cases 7 and 9 was not performed. The electrophysiological abnormalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generalized brain atrophy and unique type of neuronal cytoplasmic inclusion body in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebral cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Kluver-Barrera method. They were unstained with ConA and distinctly varied ranging from negative to strong positive with Sudan BB. These lysosomal inclusions correspond to unusually densely packed curvilinear profiles which in some cells formed large aggregates almost entirely filling the neuronal cytoplasm. Neurons of other grey matter regions, however, showed loosely arranged curvilinear profiles that were surrounded by single membranes and sometimes intermixed with finger print profiles, similar as described in the classical LINCL cases. The cerebellum showed unusually severe atrophy. This new variant of Jansky-Bielschowsky disease stresses the heterogeneity within this particular subform of LINCL. Further biochemical and genetic studies are needed to better define these different subforms of NCL cases.",,"Wisniewski, K. E.;Kida, E.;Connell, F.;Elleder, M.;Eviatar, L.;Konkol, R. J.",1993,1993,,0,
322,An MRI study of age-related white and gray matter volume changes in the rhesus monkey,"We applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to dual-echo spin echo (DE SE) images of eight young (5-12 years), six middle-aged (16-19 years) and eight old (24-30 years) rhesus monkeys. We analyzed standardized mean volumes for 18 anatomically defined regions of interest (ROI's) and found an overall decrease from young to old age in the total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%). Corresponding behavioral data for five of the young, five of the middle-aged and seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the Delayed-recognition Span Task (DRST) and the Cognitive Impairment Index (CII) were also analyzed. We found that none of the cognitive measures were related to ROI volume changes in our sample size of monkeys.","Aging/ pathology;Alzheimer Disease/pathology/physiopathology;Animals;Atrophy/ pathology/physiopathology;Brain/ pathology/physiopathology;Brain Mapping;Cerebral Cortex/pathology/physiopathology;Cognition Disorders/etiology/pathology/physiopathology;Disease Progression;Macaca mulatta/ anatomy & histology/physiology;Magnetic Resonance Imaging;Male;Memory Disorders/ pathology/physiopathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Organ Size","Wisco, J. J.;Killiany, R. J.;Guttmann, C. R.;Warfield, S. K.;Moss, M. B.;Rosene, D. L.",2008,Oct,10.1016/j.neurobiolaging.2007.03.022,0,
323,"Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people","IMPORTANCE: Criteria for preclinical Alzheimer disease (AD) propose beta-amyloid (Abeta) plaques to initiate neurodegeneration within AD-affected regions. However, some cognitively normal older individuals harbor neural injury similar to patients with AD, without concurrent Abeta burden. Such findings challenge the proposed sequence and suggest that Abeta-independent precursors underlie AD-typical neurodegenerative patterns. OBJECTIVE To examine relationships between Abeta and non-Abeta factors as well as neurodegeneration within AD regions in cognitively normal older adults. The study quantified neurodegenerative abnormalities using imaging biomarkers and examined cross-sectional relationships with Abeta deposition; white matter lesions (WMLs), a marker of cerebrovascular disease; and cognitive functions. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in a community-based convenience sample of 72 cognitively normal older individuals (mean [SD] age, 74.9 [5.7] years; 48 women; mean [SD] 17.0 [1.9] years of education) of the Berkeley Aging Cohort. INTERVENTION: Each individual underwent a standardized neuropsychological test session, magnetic resonance imaging, and positron emission tomography scanning. MAIN OUTCOMES AND MEASURES: For each individual, 3 AD-sensitive neurodegeneration biomarkers were measured: hippocampal volume, glucose metabolism, and gray matter thickness, the latter 2 sampled from cortical AD-affected regions. To quantify neurodegenerative abnormalities, each biomarker was age adjusted, dichotomized into a normal or abnormal status (using cutoff thresholds derived from an independent AD sample), and summarized into 0, 1, or more than 1 abnormal neurodegenerative biomarker. Degree and topographic patterns of neurodegenerative abnormalities were assessed and their relationships with cognitive functions, WML volume, and Abeta deposition (quantified using carbon 11-labeled Pittsburgh compound B positron emission tomography). RESULTS: Of our cognitively normal elderly individuals, 40% (n = 29) displayed at least 1 abnormal neurodegenerative biomarker, 26% (n = 19) of whom had no evidence of elevated Pittsburgh compound B retention. In those people who were classified as having abnormal cortical thickness, degree and topographic specificity of neurodegenerative abnormalities were similar to patients with AD. Accumulation of neurodegenerative abnormalities was related to poor memory and executive functions as well as larger WML volumes but not elevated Pittsburgh compound B retention. CONCLUSIONS AND RELEVANCE: Our study confirms that a substantial proportion of cognitively normal older adults harbor neurodegeneration, without Abeta burden. Associations of neurodegenerative abnormalities with cerebrovascular disease and cognitive performance indicate that neurodegenerative pathology can emerge through non-Abeta pathways within regions most affected by AD.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/ diagnosis/radionuclide imaging;Aniline Compounds;Biomarkers/metabolism;Cognition Disorders/ etiology/radionuclide imaging;Cohort Studies;Community-Based Participatory Research;Cross-Sectional Studies;Female;Fluorodeoxyglucose F18;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Neurodegenerative Diseases/ etiology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography;Psychiatric Status Rating Scales;Thiazoles","Wirth, M.;Villeneuve, S.;Haase, C. M.;Madison, C. M.;Oh, H.;Landau, S. M.;Rabinovici, G. D.;Jagust, W. J.",2013,Dec,10.1001/jamaneurol.2013.4013,0,
324,"Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults","This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Abeta) burden, cerebrovascular lesions, and neural injury within the brain regions affected in Alzheimer's disease (AD). Ninety-two cognitively normal older adults (75.2 +/- 5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Abeta burden (using [(11)C] labeled Pittsburgh-Compound-B positron emission tomography), cerebrovascular lesions (using magnetic resonance imaging-defined white matter lesion [WML]), and neural integrity within AD regions (using a multimodal neuroimaging biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower [(11)C] labeled Pittsburgh-Compound-B retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Abeta pathology thought to be relevant to AD development.","Aged;Aged, 80 and over;Aging/ pathology/physiology/ psychology;Alzheimer Disease/etiology/ prevention & control;Amyloid beta-Peptides/ metabolism;Brain/ metabolism/ pathology;Cognition/ physiology;Female;Humans;Life Style;Magnetic Resonance Imaging;Male;Motor Activity/ physiology;Positron-Emission Tomography;Surveys and Questionnaires","Wirth, M.;Haase, C. M.;Villeneuve, S.;Vogel, J.;Jagust, W. J.",2014,Aug,10.1016/j.neurobiolaging.2014.02.015,0,
325,Associations of Brain Structure With Adiposity and Changes in Adiposity in a Middle-Aged and Older Biracial Population,"Background: Studies of adiposity and brain pathology in African Americans (AA) are sparse despite higher rates of obesity, dementia, and dementia-associated brain pathology in AA. This study examined relations of adiposity to white matter hyperintensities (WMH) and total brain volume (TBV) in AA and non-Hispanic whites (NHW). Methods: Waist circumference (WC) and body mass index (BMI) were measured in the Genetic Epidemiology Network of Arteriopathy study at Visits 1 (mean age 57 [+/-11]) and 2 (mean age 61 [+/-10], mean 5.2 years later). Brain MRIs were obtained shortly after Visit 2 in 1,702 participants (64% women, 48% AA). Multilevel linear regression using generalized estimating equation estimated associations of adiposity (cross-sectional) or adiposity changes with WMH (accounting for intracranial size) or TBV adjusting for demographics, cardiovascular risk factors, and incorporating adiposity-by-race interactions. Adiposity-by-age interactions were examined. Results: Concurrent TBV was inversely associated with BMI (beta = -2.76 [95% confidence interval (CI): -4.99, -0.53]) and WC (beta = -2.19 [CI: -4.04, -0.34]). Concurrent WMH were negatively associated with BMI (beta = -0.04 [CI: -0.06, -0.01]) and, among NHW, with WC (beta = -0.04 [CI: -0.06, -0.02]) but not with changes in BMI or WC. BMI increases were associated with lower TBV (beta = -16.20, [CI: -30.34, -2.06]) in AA but not in NHW (beta = -2.76 [CI: -14.02, 8.51]), although race-by-adiposity interactions were not supported. WC increases were not associated with MRI outcomes. Conclusion: Greater measures of obesity and increases in measures of obesity, which are common in mid-life, could be detrimental to brain health, particularly in AA.",African Americans;Aging;Body Mass Index;Brain/ diagnostic imaging;European Continental Ancestry Group;Female;Humans;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Minnesota/epidemiology;Mississippi/epidemiology;Obesity/ epidemiology;Waist Circumference;White Matter/ diagnostic imaging;Longitudinal;Mri;Obesity;Race,"Windham, B. G.;Lirette, S. T.;Fornage, M.;Benjamin, E. J.;Parker, K. G.;Turner, S. T.;Jack, C. R., Jr.;Griswold, M. E.;Mosley, T. H.",2017,Jun 1,,0,326
326,Associations of Brain Structure With Adiposity and Changes in Adiposity in a Middle-Aged and Older Biracial Population,"BACKGROUND: Studies of adiposity and brain pathology in African Americans (AA) are sparse despite higher rates of obesity, dementia, and dementia-associated brain pathology in AA. This study examined relations of adiposity to white matter hyperintensities (WMH) and total brain volume (TBV) in AA and non-Hispanic whites (NHW). METHODS: Waist circumference (WC) and body mass index (BMI) were measured in the Genetic Epidemiology Network of Arteriopathy study at Visits 1 (mean age 57 [+/-11]) and 2 (mean age 61 [+/-10], mean 5.2 years later). Brain MRIs were obtained shortly after Visit 2 in 1,702 participants (64% women, 48% AA). Multilevel linear regression using generalized estimating equation estimated associations of adiposity (cross-sectional) or adiposity changes with WMH (accounting for intracranial size) or TBV adjusting for demographics, cardiovascular risk factors, and incorporating adiposity-by-race interactions. Adiposity-by-age interactions were examined. RESULTS: Concurrent TBV was inversely associated with BMI (beta = -2.76 [95% confidence interval (CI): -4.99, -0.53]) and WC (beta = -2.19 [CI: -4.04, -0.34]). Concurrent WMH were negatively associated with BMI (beta = -0.04 [CI: -0.06, -0.01]) and, among NHW, with WC (beta = -0.04 [CI: -0.06, -0.02]) but not with changes in BMI or WC. BMI increases were associated with lower TBV (beta = -16.20, [CI: -30.34, -2.06]) in AA but not in NHW (beta = -2.76 [CI: -14.02, 8.51]), although race-by-adiposity interactions were not supported. WC increases were not associated with MRI outcomes. CONCLUSION: Greater measures of obesity and increases in measures of obesity, which are common in mid-life, could be detrimental to brain health, particularly in AA.",Longitudinal;Mri;Obesity;Race,"Windham, B. G.;Lirette, S. T.;Fornage, M.;Benjamin, E. J.;Parker, K. G.;Turner, S. T.;Jack, C. R., Jr.;Griswold, M. E.;Mosley, T. H.",2016,Dec 18,,0,
327,Corpus callosum and cingulum tractography in Parkinson's disease,"BACKGROUND: In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts. OBJECTIVE: To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients. METHODS: Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1 F) and controls (8 M, 7 F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes. RESULTS: Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume. CONCLUSIONS: The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.","Aged;Corpus Callosum/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Gyrus Cinguli/ pathology;Humans;Imaging, Three-Dimensional/methods;Male;Mental Status Schedule;Parkinson Disease/ pathology","Wiltshire, K.;Concha, L.;Gee, M.;Bouchard, T.;Beaulieu, C.;Camicioli, R.",2010,Sep,,0,
328,Syntactic processing depends on dorsal language tracts,"Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts-the superior longitudinal fasciculus including its arcuate component-was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts-the extreme capsule fiber system or the uncinate fasciculus-was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts. © 2011 Elsevier Inc.",,"Wilson, S.;Galantucci, S.;Tartaglia, M.;Rising, K.;Patterson, D.;Henry, M.;Ogar, J.;DeLeon, J.;Miller, B.;Gorno-Tempini, M.",2011,20,,0,
329,"Establishing the ""meaning"" of microbleeds: Clinical context or lobar microbleed burden?",,brain hemorrhage;cohort analysis;community;dementia;diagnostic test accuracy study;diagnostic value;disease severity;hemisphere;hospital;human;letter;neuroimaging;neurologic disease;neuropathology;nuclear magnetic resonance imaging;positron emission tomography;predictive value;prevalence;priority journal;risk factor;sensitivity and specificity;vascular amyloidosis,"Wilson, D.;Werring, D. J.",2016,,,0,
330,Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: A randomized clinical trial,"IMPORTANCE: Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. OBJECTIVE: To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS: A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A(1c) (HbA(1c)) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. MAIN OUTCOME MEASURES: Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. RESULTS: Baseline mean HbA(1c) level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, -4.4 [95% CI, -7.8 to -1.1] cm(3); P = .01). Fibrate therapy had no effect on TBV compared with placebo. CONCLUSIONS AND RELEVANCE: In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000620 Copyright 2014 American Medical Association. All rights reserved.",,"Williamson, J. D.;Launer, L. J.;Bryan, N.;Coker, L. H.;Lazar, R. M.;Gerstein, H. C.;Murray, A. M.;Sullivan, M. D.;Horowitz, K. R.;Ding, J.;Marcovina, S.;Lovato, L.;Lovato, J.;Margolis, K. L.;Davatzikos, C.;Barzilay, J.;Ginsberg, H. N.;Linz, P. E.;Miller, M. E.",2014,March,,0,
331,Baseline differences between vascular cognitive impairment no dementia reverters and non-reverters,"BACKGROUND: The underlying factors of reversion from cognitive impairment to normal cognitive functioning in stroke are not well understood. We compare demographic, cognitive and imaging factors in Vascular Cognitive Impairment, No Dementia (Vascular CIND) patients who revert to normal cognitive functioning to Vascular CIND patients who do not revert. METHODS: Thirty-one ischaemic stroke patients, who met classification criteria for Vascular CIND, were >49.5 years old, met NINDS stroke criteria, and were free from additional neurological illness, completed baseline and 1-year examinations. Forty-five per cent of the Vascular CIND participants reverted to no cognitive impairment at 1-year follow-up examination. RESULTS: There was greater cognitive impairment in non-reverters on a summary score spanning several neuropsychological domains and on psychomotor and working memory summary scores. There were no differences on demographic factors or in stroke severity between reverters and non-reverters. Structural MRI analyses revealed no baseline differences in number of strokes, stroke volume or stroke location. However, there was greater frontal white matter hyperintensity load in the non-reverter group. CONCLUSIONS: These results suggest that Vascular CIND reversion may be a function of a combination of baseline neuropsychological function and location of cerebrovascular disease.","Aged;Atrophy/pathology;Brain/blood supply/pathology/physiopathology;Cerebrovascular Circulation/physiology;Cognition Disorders/diagnosis/ etiology;Dementia, Vascular/ complications/ physiopathology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychomotor Disorders/diagnosis/etiology;Severity of Illness Index","Williamson, J. B.;Nyenhuis, D. L.;Pedelty, L.;Byrd, S.;Jhaveri, M.;Wang, C.;deToledo-Morrell, L.;Sripathirathan, K.;Gorelick, P.",2008,Nov,10.1136/jnnp.2007.137554,0,
332,Distinguishing primary angiitis of the central nervous system from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: The importance of family history,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically linked neurologic disease characterized by recurrent strokes and progressive or stepwise dementia, with or without migraine-like headaches, seizures, and pseudobulbar palsy. We describe a patient referred with a diagnosis of treatment-refractory primary angiitis of the central nervous system. Meningocortical and skin biopsies confirmed that the patient had CADASIL. Clinical and radiographic differences in these disorders may be subtle, but awareness of them is crucial if the patient is to avoid unnecessary exposure to potentially deleterious immunosuppressive therapy.",adult;artery disease;article;autosomal dominant disorder;brain angiography;brain artery;brain biopsy;brain infarction;case report;central nervous system;family history;female;human;human tissue;leukoencephalopathy;nuclear magnetic resonance imaging;priority journal;vasculitis,"Williamson, E. E.;Chukwudelunzu, F. E.;Meschia, J. F.;Witte, R. J.;Dickson, D. W.;Cohen, M. D.",1999,,,0,
333,Retinal microvascular network attenuation in Alzheimer's disease,"INTRODUCTION: Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. METHODS: Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. RESULTS: Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62-0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63-0.97]) were more likely to have AD after appropriate adjustment. DISCUSSION: Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD.",,"Williams, M. A.;McGowan, A. J.;Cardwell, C. R.;Cheung, C. Y.;Craig, D.;Passmore, P.;Silvestri, G.;Maxwell, A. P.;McKay, G. J.",2015,Jun,10.1016/j.dadm.2015.04.001,0,
334,Lipid profile components and subclinical cerebrovascular disease in the northern Manhattan study,"BACKGROUND: Subclinical cerebrovascular disease has been associated with multiple adverse events related to aging, including stroke and dementia. The modifiable risk factors for subclinical cerebrovascular disease beyond hypertension have not been well characterized. Our objective was to examine the association between baseline, and changes over time, in lipid profile components and subclinical cerebrovascular disease on magnetic resonance imaging (MRI). METHODS: Fasting plasma lipids were collected on participants in the Northern Manhattan Study, a prospective cohort study examining risk factors for cardiovascular disease in a multiethnic elderly urban-dwelling population. A subsample of the cohort underwent brain MRI between 2003 and 2008 (a median of 6.2 years, range = 0-14, after enrollment), when repeat fasting lipids were obtained. We used lipid profile components at the time of initial enrollment (n = 1,256 with lipids available) as categorical variables, as well as change in clinical categories over the two measures (n = 1,029). The main outcome measures were (1) total white matter hyperintensity volume (WMHV) using linear regression and (2) silent brain infarcts (SBI) using logistic regression. RESULTS: None of the plasma lipid profile components at the time of enrollment were associated with WMHV. The association between baseline lipids and WMHV was, however, modified by apolipoprotein E (apoE) status (chi(2) with 2 degrees of freedom, p = 0.03), such that among apoE4 carriers those with total cholesterol (TC) >/=200 mg/dl had a trend towards smaller WMHV than those with TC <200 mg/dl (difference in logWMHV -0.19, p = 0.07), while there was no difference among apoE3 carriers. When examining the association between WMHV and change in lipid profile components we noted an association with change in high-density lipoprotein cholesterol (HDL-C, >50 mg/dl for women, >40 mg/dl for men) and TC. A transition from low-risk HDL-C (>50 mg/dl for women, >40 mg/dl for men) at baseline to high-risk HDL-C at the time of MRI (vs. starting and remaining low risk) was associated with greater WMHV (difference in logWMHV 0.34, p value 0.03). We noted a similar association with transitioning to a TC >/=200 mg/dl at the time of MRI (difference in logWMHV 0.25, p value 0.006). There were no associations with baseline or change in lipid profile components with SBI. CONCLUSIONS: The association of plasma lipid profile components with greater WMHV may depend on apoE genotype and worsening HDL and TC risk levels over time.","Adult;Aged;Aged, 80 and over;Aging;Apolipoproteins E/genetics;Cholesterol/ blood;Cohort Studies;Female;Humans;Lipid Metabolism;Lipoproteins, HDL/ blood;Lipoproteins, LDL;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Risk Factors;Stroke/ etiology/genetics","Willey, J. Z.;Gardener, H.;Moon, Y. P.;Yoshita, M.;DeCarli, C.;Cheung, Y. K.;Sacco, R. L.;Elkind, M. S.;Wright, C. B.",2014,,10.1159/000362920,0,
335,Leisure-time physical activity associates with cognitive decline,"Objective: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. Methods: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n 1,228), and a repeat examination was performed 5 years later (n 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). Results: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β -0.231 ± 0.112, p 0.040) and episodic memory (β -0.223 ± 0.117, p 0.057) adjusting for sociodemographic and vascular risk factors. Conclusions: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.",aged;article;brain infarction;brain size;cardiovascular disease;cognitive defect;dementia;episodic memory;executive function;female;human;leisure;major clinical study;male;neuropsychological test;nuclear magnetic resonance imaging;physical activity;priority journal;questionnaire;semantic memory;white matter,"Willey, J. Z.;Gardener, H.;Caunca, M. R.;Moon, Y. P.;Dong, C.;Cheung, Y. K.;Sacco, R. L.;Elkind, M. S. V.;Wright, C. B.",2016,,,0,
336,Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study,"OBJECTIVE: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. METHODS: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). RESULTS: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (beta = -0.231 +/- 0.112, p = 0.040) and episodic memory (beta = -0.223 +/- 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. CONCLUSIONS: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.",Aged;Brain/diagnostic imaging;Cognitive Dysfunction/diagnostic imaging/ epidemiology/physiopathology;Exercise/ psychology;Female;Humans;Incidence;Leisure Activities;Linear Models;Magnetic Resonance Imaging;Male;Multivariate Analysis;Neuropsychological Tests;New York City/epidemiology;Prevalence;Prospective Studies,"Willey, J. Z.;Gardener, H.;Caunca, M. R.;Moon, Y. P.;Dong, C.;Cheung, Y. K.;Sacco, R. L.;Elkind, M. S.;Wright, C. B.",2016,May 17,,0,
337,Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study,"OBJECTIVE: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. METHODS: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). RESULTS: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (beta = -0.231 +/- 0.112, p = 0.040) and episodic memory (beta = -0.223 +/- 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. CONCLUSIONS: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.",,"Willey, J. Z.;Gardener, H.;Caunca, M. R.;Moon, Y. P.;Dong, C.;Cheung, Y. K.;Sacco, R. L.;Elkind, M. S.;Wright, C. B.",2016,Mar 23,10.1212/wnl.0000000000002582,0,336
338,Does the brain shrink as the waist expands?,"Recent studies suggest that being overweight or obese is related to worse cognitive performance, particularly executive function. Obesity may also increase the risk of Alzheimer's disease. Consequently, there has been increasing interest in whether adiposity is related to gray or white matter (GM, WM) atrophy. In this review, we identified and critically evaluated studies assessing obesity and GM or WM volumes either globally or in specific regions of interest (ROIs). Across all ages, higher adiposity was consistently associated with frontal GM atrophy, particularly in prefrontal cortex. In children and adults <40 years of age, most studies found no relationship between adiposity and occipital or parietal GM volumes, whereas findings for temporal lobe were mixed. In middle-aged and aged adults, a majority of studies found that higher adiposity is associated with parietal and temporal GM atrophy, whereas results for precuneus, posterior cingulate, and hippocampus were mixed. Higher adiposity had no clear association with global or regional WM in any age group. We conclude that higher adiposity may be associated with frontal GM atrophy across all ages and parietal and temporal GM atrophy in middle and old age.",obesity;brain atrophy;white matter;body mass;gray matter;frontal lobe;brain;cognition;nuclear magnetic resonance imaging;atrophy;adult;temporal lobe;precuneus;hippocampus;executive function;human;child;middle aged;posterior cingulate;prefrontal cortex;groups by age;senescence;risk;Alzheimer disease,"Willette, A. A.;Kapogiannis, D.",2014,,,0,
339,"Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys","Higher serum homocysteine (Hcy) levels in humans are associated with vascular pathology and greater risk for dementia, as well as lower global and regional volumes in frontal lobe and hippocampus. Calorie restriction (CR) in rhesus monkeys (Macaca mulatta) may confer neural protection against age- or Hcy-related vascular pathology. Hcy was collected proximal to a magnetic resonance imaging (MRI) acquisition in aged rhesus monkeys and regressed against volumetric and diffusion tensor imaging indexes using voxel-wise analyses. Higher Hcy was associated with lower white matter volume in pons and corpus callosum. Hcy was correlated with lower gray matter volume and density in prefrontal cortices and striatum. CR did not influence Hcy levels. However, control monkeys exhibited a strong negative correlation between Hcy and global gray matter, whereas no relationship was evident for the CR monkeys. Similar group differences were also seen across modalities in the splenium of the corpus callosum, prefrontal cortices, hippocampus, and somatosensory areas. The data suggest that CR may ameliorate the influence of Hcy on several important age-related parameters of parenchymal health.","Age Factors;Analysis of Variance;Animals;Atrophy/pathology;Brain/ pathology;Brain Mapping;Caloric Restriction;Diffusion Tensor Imaging;Female;Homocysteine/ blood;Image Processing, Computer-Assisted;Macaca mulatta/blood/physiology;Magnetic Resonance Imaging;Male","Willette, A. A.;Gallagher, C.;Bendlin, B. B.;McLaren, D. G.;Kastman, E. K.;Canu, E.;Kosmatka, K. J.;Field, A. S.;Alexander, A. L.;Colman, R. J.;Voytko, M. L.;Weindruch, R. H.;Coe, C. L.;Johnson, S. C.",2012,Apr,10.1016/j.neurobiolaging.2010.06.003,0,
340,Cerebral magnetic resonance relaxometry in HIV infection,"A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.","AIDS Dementia Complex/diagnosis;AIDS-Related Opportunistic Infections/diagnosis;Adult;Blood Donors;Brain/*pathology;Brain Diseases/complications/diagnosis;CD4 Lymphocyte Count;Cross-Sectional Studies;Female;HIV Infections/immunology/*pathology;HIV Seronegativity;HIV Seropositivity/pathology;*Hiv-1;Homosexuality, Male;Humans;*Magnetic Resonance Imaging;Male;Prospective Studies;Risk Factors","Wilkinson, I. D.;Paley, M. N.;Hall-Craggs, M. A.;Chinn, R. J.;Chong, W. K.;Sweeney, B. J.;Kendall, B. E.;Miller, R. F.;Newman, S. P.;Harrison, M. J.",1996,,,0,
341,Short echo-time proton magnetic resonance spectroscopy in regions of severe HIV-related diffuse white matter abnormality on MRI,"The purpose of this study was to determine whether short echo-time proton magnetic resonance spectroscopy (H-MRS) could detect mobile lipid resonances attributable to myelin breakdown products in the deep cerebral white matter of patients with AIDS who have severe diffuse/patchy white matter hyperintensity on T2-weighted magnetic resonance imaging (MRI). Seven patients with AIDS and clinical HIV-associated dementia complex (HADC) and 12 male controls were studied at 1.5T using a single 8 ml voxel, gradient localised, stimulated echo acquisition mode (STEAM) spectroscopy sequence. Spectra were acquired at an echo time of 20 ms with a repetition time of 5000 ms. No spectroscopic peaks were identified at 0.9 ppm and 1.3 ppm (corresponding to lipid resonances) in 6 of the 7 patients with AIDS or in any of the controls. Lipid resonances were identified in 1 patient who had been taking anti-retroviral therapy for 8 weeks. Follow up MRI/H-MRS, performed after a further 14 weeks of anti-retroviral therapy, showed partial resolution of white matter hyperintensity and lipid resonances were not detectable. These data suggest that mobile lipids are only rarely detected by H-MRS in patients with HADC and abnormalities on MRI and that their presence may be transitory.","AIDS Arteritis, Central Nervous System/ diagnosis/pathology;AIDS-Related Opportunistic Infections/diagnosis/pathology;Adult;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged","Wilkinson, I. D.;Miller, R. F.;Hall-Craggs, M. A.;Paley, M. N.;Harrison, M. J.",1998,,10.1300/J128v02n01_04,0,
342,Proton MRS and quantitative MRI assessment of the short term neurological response to antiretroviral therapy in AIDS,"OBJECTIVE: To investigate MRI and proton spectroscopy changes in five patients with HIV associated dementia complex (HADC) treated with antiretroviral therapy. METHODS: Three markers were evaluated: (1) CSF/intracranial volume ratio; (2) T2 weighted signal ratio between parieto-occipital white and subcortical grey matter; and (3) metabolite ratios from long echo time (TE=135 ms) single voxel proton spectra of parieto-occipital white matter. RESULTS: Spectroscopic changes indicated initial increases in N-acetyl/(N-acetyl + choline + creatine) ratio (NA/(NA+ Cho+Cr)) and progression of atrophy after initiation of antiretroviral therapy in four of five patients. When the neurological status of the patients subsequently deteriorated (two of five patients), the NA/(NA+Cho+Cr) ratio also declined. CONCLUSIONS: Spectroscopic changes mirror reversible neuronal dysfunction. These objective, non-invasive techniques may be used for monitoring the neurological effects of antiretroviral drug therapy in patients with HADC.",AIDS Dementia Complex/*drug therapy/pathology;Adult;Antiviral Agents/*therapeutic use;Humans;*Magnetic Resonance Imaging;Male;Occipital Lobe/pathology;Parietal Lobe/pathology;Zidovudine/*therapeutic use,"Wilkinson, I. D.;Lunn, S.;Miszkiel, K. A.;Miller, R. F.;Paley, M. N.;Williams, I.;Chinn, R. J.;Hall-Craggs, M. A.;Newman, S. P.;Kendall, B. E.;Harrison, M. J.",1997,Oct,,0,
343,Sub-cortical white-grey matter contrast on MRI as a quantitative marker of diffuse HIV-related parenchymal abnormality,"White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (> or = 200 x 10(6)/I) and low (< 200 x 10(6)/I) CD4 lymphocyte counts (P < 0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P < 0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.",AIDS Dementia Complex/immunology/ pathology;Adult;Analysis of Variance;Brain/ pathology;Female;Humans;Lymphocyte Count;Magnetic Resonance Imaging;Male;Middle Aged;Observer Variation;Risk Factors,"Wilkinson, I. D.;Chinn, R. J.;Hall-Craggs, M. A.;Kendall, B. E.;Paley, M. N.;Plummer, D. L.;Miller, R. F.;Harrison, M. J.",1996,Jul,,0,
344,"Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure","BACKGROUND AND PURPOSE: Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. METHODS: Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. RESULTS: A 2-mug/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. CONCLUSIONS: Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons.",Age Factors;Aged;Air Pollutants/ adverse effects;Atrophy;Brain/ pathology;Cerebral Infarction/epidemiology/pathology;Environmental Exposure;Female;Hippocampus/pathology;Humans;Male;Middle Aged;Particulate Matter/ adverse effects;Socioeconomic Factors;White Matter/pathology,"Wilker, E. H.;Preis, S. R.;Beiser, A. S.;Wolf, P. A.;Au, R.;Kloog, I.;Li, W.;Schwartz, J.;Koutrakis, P.;DeCarli, C.;Seshadri, S.;Mittleman, M. A.",2015,May,10.1161/strokeaha.114.008348,0,
345,"Fine Particulate Matter, Residential Proximity to Major Roads, and Markers of Small Vessel Disease in a Memory Study Population","Background: Long-term exposure to ambient air pollution has been associated with impaired cognitive function and vascular disease in older adults, but little is known about these associations among people with concerns about memory loss. Objective: To examine associations between exposures to fine particulate matter and residential proximity to major roads and markers of small vessel disease. Methods: From 20042010, 236 participants in the Massachusetts Alzheimer's Disease Research Center Longitudinal Cohort participated in neuroimaging studies. Residential proximity to major roads and estimated 2003 residential annual average of fine particulate air pollution (PM2.5) were linked to measures of brain parenchymal fraction (BPF), white matter hyperintensities (WMH), and cerebral microbleeds. Associations were modeled using linear and logistic regression and adjusted for clinical and lifestyle factors. Results: In this population (median age [interquartile range]=74 [12], 57 female) living in a region with median 2003 PM2.5 annual average below the current Environmental Protection Agency (EPA) standard, there were no associations between living closer to a major roadway or for a 2μg/m3 increment in PM2.5 and smaller BPF, greater WMH volume, or a higher odds of microbleeds. However, a 2μg/m3 increment in PM2.5 was associated with 0.19 (95 Confidence Interval (CI): 0.37, 0.005) lower natural log-transformed WMH volume. Other associations had wide confidence intervals. Conclusions: In this population, where median 2003 estimated PM2.5 levels were below the current EPA standard, we observed no pattern of association between residential proximity to major roads or 2003 average PM2.5 and greater burden of small vessel disease or neurodegeneration.",aged;air pollution;Alzheimer disease;article;brain parenchymal fraction;brain size;cerebrovascular disease;controlled study;disease association;disease marker;environmental exposure;female;fine particulate matter;highway;human;longitudinal study;major clinical study;male;mild cognitive impairment;nervous system parameters;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;outcome assessment;particulate matter;priority journal;residential area;residential proximity;secondary analysis;white matter;whole body scanner;1.5 Tesla Signa;3 Tesla Trio,"Wilker, E. H.;Martinez-Ramirez, S.;Kloog, I.;Schwartz, J.;Mostofsky, E.;Koutrakis, P.;Mittleman, M. A.;Viswanathan, A.",2016,,,0,
346,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Chinese family: Clinical, radiological and skin biopsy features","We describe the clinical, radiological, genetic and skin biopsy findings of the first Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family tree extending over three generations, eight had typical clinical features of CADASIL with recurrent ischemic stroke. In the three surviving affected family members, brain MRI showed extensive leukoaraiosis. Genotyping revealed heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical features were cerebellar infarction as a presenting complaint and a late age of onset with mild symptoms at age 69. A novel finding is the suggestion of a direct correlation between clinical disease severity and the quantity of ultrastructural pathognomonic granular osmophilic material (GOM) seen on skin biopsy. © 2003 Elsevier Ltd. All rights reserved.",aged;article;CADASIL;case report;cerebrovascular accident;Chinese;clinical feature;disease severity;female;gene mutation;genotype;human;leukoaraiosis;neuroimaging;nuclear magnetic resonance imaging;priority journal;skin biopsy,"Wilder-Smith, E.;Shen, Y.;Ng, Y. K.;Yu, G. X.;Chew, N. K.;Tan, C. T.;Wong, M. C.",2004,,,0,
347,Shorter telomere length is linked to brain atrophy and white matter hyperintensities,"BACKGROUND: leukocyte telomere length (TL) is considered a marker of biological aging. Several studies have investigated the link between leukocyte TL and aging-associated functional attributes of the brain, but no prior study has investigated whether TL can be linked to brain atrophy and white matter hyperintensities (WMHs); two prominent structural manifestations of brain aging. METHODS: we investigated whether leukocyte TL was related to brain atrophy and WMHs in a sample of 102 non-demented individuals aged 64-75 years. RESULTS: shorter TL was related to greater degree of subcortical atrophy (beta = -0.217, P = 0.034), but not to cortical atrophy. Furthermore, TL was 371 bp shorter (P = 0.041) in participants exhibiting subcortical WMHs, and 552 bp shorter (P = 0.009) in older participants exhibiting periventricular WMHs. CONCLUSION: this study provides the first evidence of leukocyte TL being associated with cerebral subcortical atrophy and WMHs, lending further support to the concept of TL as a marker of biological aging, and in particular that of the aging brain.",Age Factors;Aged;Aging/genetics/pathology;Atrophy;Biomarkers/blood;Brain/*pathology;Female;Humans;Leukocytes/*chemistry;Leukoencephalopathies/blood/*genetics/*pathology;Magnetic Resonance Imaging;Male;Middle Aged;Telomere/*chemistry;*Telomere Shortening;brain atrophy;older people;telomere length;white matter hyperintensities,"Wikgren, M.;Karlsson, T.;Soderlund, H.;Nordin, A.;Roos, G.;Nilsson, L. G.;Adolfsson, R.;Norrback, K. F.",2014,Mar,10.1093/ageing/aft172,0,
348,A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice,"APOE epsilon4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging.","0 (Apolipoprotein E4);0 (Apolipoproteins E);0 (Fatty Acids);0 (Membrane Proteins);0 (Sterols);EC 2.7.4.8 (Dlgh4 protein, mouse);EC 2.7.4.8 (Guanylate Kinases);Aging;Alzheimer Disease/ diet therapy/genetics/ physiopathology;Animals;Apolipoprotein E4/genetics;Apolipoproteins E/genetics;Brain/ blood supply/metabolism/ physiopathology;Brain Mapping;Diet;Fatty Acids/metabolism;Female;Guanylate Kinases/metabolism;Magnetic Resonance Imaging;Male;Membrane Proteins/metabolism;Mice;Mice, Inbred C57BL;Mice, Transgenic;Neural Pathways/blood supply/metabolism/physiopathology;Sterols/blood","Wiesmann, M.;Zerbi, V.;Jansen, D.;Haast, R.;Lutjohann, D.;Broersen, L. M.;Heerschap, A.;Kiliaan, A. J.",2016,,,0,
349,Cerebral microbleeds in a multiethnic elderly community: Demographic and clinical correlates,"Background: Microbleeds, small perivascular collections of hemosiderin manifested radiologically as hypointensities on gradient-echo magnetic resonance imaging (MRI), are important markers of small vessel pathology. Despite their clinical relevance, little is known about their prevalence and demographic correlates, particularly among ethnically diverse older adults. We examined demographic and clinical correlates of regional microbleeds in a multi-ethnic cohort and examined categorization schemes ofmicrobleed distribution and severity. Methods: Between 2005 and 2007, 769 individuals participated in a MRI study as part of theWashington Heights/ Inwood Columbia Aging Project. Approximately four years later, 243 out of 339 participants (mean age = 84.50) who returned for a repeat MRI had gradient-echo scans for microbleed assessment and comprised the sample. We examined the association of deep and lobar microbleeds with age, sex, education, vascular factors, cognitive status and markers of small vessel disease. Results: Sixty-seven of the 243 (27%) participants had at least one microbleed. Individuals with microbleeds were more likely to have a history of stroke than individuals without.When categorized as having either nomicrobleeds, microbleeds in deep regions only, in lobar regions only, and both deep and lobar microbleeds, hypertension, proportion of strokes, and white matter hyperintensity volume (WMH) increased monotonically across the four groups. The number of lobar microbleeds correlated withWMH volume and diastolic blood pressure. Conclusions: Microbleeds in deep and lobar locations are associated with worse outcomes than microbleeds in either location alone, although the presence of lobar microbleeds appears to be more clinically relevant.",,"Wiegman, A. F.;Meier, I. B.;Schupf, N.;Manly, J. J.;Guzman, V. A.;Narkhede, A.;Stern, Y.;Martinez-Ramirez, S.;Viswanathan, A.;Luchsinger, J. A.;Greenberg, S. M.;Mayeux, R.;Brickman, A. M.",2014,15,,0,
350,Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways,"Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimer's disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell death in experimental models of stroke and Alzheimer's disease. Treatment of cultured neurons with IVIg reduced simulated ischemia- and amyloid betapeptide (Abeta)-induced caspase 3 cleavage, and phosphorylation of the cell death-associated kinases p38MAPK, c-Jun NH2 -terminal kinase and p65, in vitro. Additionally, Abeta-induced accumulation of the lipid peroxidation product 4-hydroxynonenal was attenuated in neurons treated with IVIg. IVIg treatment also up-regulated the anti-apoptotic protein, Bcl2 in cortical neurons under ischemia-like conditions and exposure to Abeta. Treatment of mice with IVIg reduced neuronal cell loss, apoptosis and infarct size, and improved functional outcome in a model of focal ischemic stroke. Together, these results indicate that IVIg acts directly on neurons to protect them against ischemic stroke and Abeta-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bcl2.","Amyloid beta-Peptides/*antagonists & inhibitors/pharmacology/*toxicity;Animals;Blotting, Western;Brain Ischemia/pathology/*prevention & control;Brain Mapping;Cell Death/*drug effects;Cell Hypoxia/drug effects;Cell Survival/drug effects;Glucose/deficiency;Immunoglobulins, Intravenous/*pharmacology;Immunohistochemistry;In Situ Nick-End Labeling;Infarction, Middle Cerebral Artery/pathology;Magnetic Resonance Imaging;Male;Mice;Mice, Inbred C57BL;Neurons/*drug effects;*Neuroprotective Agents;Peptide Fragments/pharmacology;Proto-Oncogene Proteins c-bcl-2/biosynthesis;Signal Transduction/*drug effects;Stroke/pathology/*prevention & control;Treatment Outcome;Up-Regulation","Widiapradja, A.;Vegh, V.;Lok, K. Z.;Manzanero, S.;Thundyil, J.;Gelderblom, M.;Cheng, Y. L.;Pavlovski, D.;Tang, S. C.;Jo, D. G.;Magnus, T.;Chan, S. L.;Sobey, C. G.;Reutens, D.;Basta, M.;Mattson, M. P.;Arumugam, T. V.",2012,Jul,10.1111/j.1471-4159.2012.07754.x,0,
351,Elevated occipital β-amyloid deposition is associated with widespread cognitive impairment in logopenic progressive aphasia,"Background: Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement. Objectives: To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe. Methods: Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18-Ffluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed. Results: Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low. Conclusions: Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.",,"Whitwell, J. L.;Lowe, V. J.;Duffy, J. R.;Strand, E. A.;Machulda, M. M.;Kantarci, K.;Wille, S. M.;Senjem, M. L.;Murphy, M. C.;Gunter, J. L.;Jack Jr, C. R.;Josephs, K. A.",2013,December,,0,
352,Microbleeds in atypical presentations of Alzheimer's disease: a comparison to dementia of the Alzheimer's type,"BACKGROUND: Microbleeds in the brain have been shown to occur in Alzheimer's disease (AD), affecting approximately a third of subjects that present with typical dementia of the Alzheimer's type (DAT). However, little is known about the frequency or distribution of microbleeds in subjects with AD that present with atypical clinical presentations. OBJECTIVE: To determine whether the frequency and regional distribution of microbleeds in atypical AD differs from that observed in subjects with DAT, and to determine whether microbleeds in atypical AD are associated with age, demographics, or cognitive impairment. METHODS: Fifty-five subjects with amyloid-beta deposition on Pittsburgh compound B (PiB) PET who presented with predominant language (n = 37) or visuospatial/perceptual (n = 18) deficits underwent T2*weighted MRI. These subjects were compared to 41 PiB-positive subjects with DAT. Microbleeds were identified and assigned a lobar location. RESULTS: The proportion of subjects with microbleeds did not differ between atypical AD (42%) and DAT (32%). However, atypical AD had larger numbers of microbleeds than DAT. In addition, the topographic distribution of microbleeds differed between atypical AD and DAT, with atypical AD showing the highest density of microbleeds in the frontal lobes. Among atypical AD, number of microbleeds was associated with age, but not gender or cognition. Microbleeds were more common in subjects with language (51%) versus visuospatial/perceptual deficits (22%). CONCLUSIONS: Microbleeds are relatively common in both DAT and atypical AD, although atypical AD subjects appear to be at particular risk for developing large numbers of microbleeds and for developing microbleeds in the frontal lobe.",Aged;Alzheimer Disease/metabolism/ pathology/radionuclide imaging;Amyloid beta-Peptides/metabolism;Aniline Compounds;Brain/metabolism/ pathology/radionuclide imaging;Cerebral Hemorrhage/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Phenotype;Positron-Emission Tomography;Radiopharmaceuticals;Thiazoles,"Whitwell, J. L.;Kantarci, K.;Weigand, S. D.;Lundt, E. S.;Gunter, J. L.;Duffy, J. R.;Strand, E. A.;Machulda, M. M.;Spychalla, A. J.;Drubach, D. A.;Petersen, R. C.;Lowe, V. J.;Jack, C. R., Jr.;Josephs, K. A.",2015,,10.3233/jad-142628,0,
353,Voxel-based morphometry and its application to movement disorders,"Voxel-based morphometry (VBM) is an automated technique that assesses patterns of regional grey and white matter atrophy on MRI between two groups of subjects. VBM has been used to assess patterns of regional atrophy in subjects with movement disorders. These studies have demonstrated specific patterns of regional loss in each disorder, compared different movement disorders to look for differences that could be diagnostically useful, and have correlated regions of loss to cognitive and motor deficits in these subjects. This article will review the findings of these studies and discuss the role of VBM in movement disorders. © 2007 Elsevier Ltd. All rights reserved.",article;atrophy;cognitive defect;corticobasal degeneration;diagnostic imaging;diagnostic procedure;differential diagnosis;Huntington chorea;longitudinal study;morphometrics;motor dysfunction;Parkinson disease;priority journal;progressive supranuclear palsy;Shy Drager syndrome;spinocerebellar degeneration;voxel based morphometry,"Whitwell, J. L.;Josephs, K. A.",2007,,,0,
354,Microbleeds in the logopenic variant of primary progressive aphasia,"BACKGROUND: Microbleeds have been associated with Alzheimer's disease (AD), although it is unclear whether they occur in atypical presentations of AD, such as the logopenic variant of primary progressive aphasia (lvPPA). We aimed to assess the presence and clinical correlates of microbleeds in lvPPA. METHODS: Thirteen lvPPA subjects underwent 3T T2*-weighted and fluid-attenuated inversion recovery magnetic resonance imaging and Pittsburgh compound B (PiB) positron emission tomography imaging. Microbleeds were identified on manual review and assigned a regional location. Total and regional white matter hyperintensity (WMH) burden was measured. RESULTS: Microbleeds were observed in four lvPPA subjects (31%), most commonly in the frontal lobe. Subjects with microbleeds were older, more likely female, and had a greater burden of WMH than those without microbleeds. The regional distribution of microbleeds did not match the regional distribution of WMH. All cases were PiB positive. CONCLUSIONS: Microbleeds occur in approximately one third of subjects with lvPPA, with older women at the highest risk.","Aged;Aniline Compounds;Aphasia, Primary Progressive/ complications;Female;Hemorrhage/ etiology/radionuclide imaging;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Positron-Emission Tomography;Statistics, Nonparametric;Thiazoles;Tomography, X-Ray Computed","Whitwell, J. L.;Jack, C. R., Jr.;Duffy, J. R.;Strand, E. A.;Gunter, J. L.;Senjem, M. L.;Murphy, M. C.;Kantarci, K.;Machulda, M. M.;Lowe, V. J.;Josephs, K. A.",2014,Jan,10.1016/j.jalz.2013.01.006,0,
355,Clinical and neuroimaging biomarkers of amyloid-negative logopenic primary progressive aphasia,"Logopenic primary progressive aphasia (lvPPA) is a progressive language disorder characterized by anomia, difficulty repeating complex sentences, and phonological errors. The majority, although not all, lvPPA patients have underlying Alzheimer's disease. We aimed to determine whether clinical or neuroimaging features differ according to the deposition of Abeta on Pittsburgh-compound B PET in lvPPA. Clinical features, patterns of atrophy on MRI, hypometabolism on FDG-PET, and white matter tract degeneration were compared between six PiB-negative and 20 PiB-positive lvPPA patients. PiB-negative patients showed more asymmetric left-sided patterns of atrophy, hypometabolism and white matter tract degeneration, with greater left anteromedial temporal and medial prefrontal involvement, than PiB-positive patients. PiB-positive patients showed greater involvement of right temporoparietal and frontal lobes. There was very little evidence for clinical differences between the groups. Strikingly asymmetric neuroimaging findings with relatively preserved right hemisphere may provide clues that AD pathology is absent in lvPPA.","Aged;Alzheimer Disease/ diagnosis/pathology;Amyloid beta-Peptides/ analysis;Aphasia, Primary Progressive/ diagnosis/pathology;Atrophy;Biomarkers/ analysis;Brain Mapping;Cerebral Cortex/pathology/physiopathology/radionuclide imaging;Dominance, Cerebral/physiology;Female;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography","Whitwell, J. L.;Duffy, J. R.;Strand, E. A.;Machulda, M. M.;Senjem, M. L.;Schwarz, C. G.;Reid, R.;Baker, M. C.;Perkerson, R. B.;Lowe, V. J.;Rademakers, R.;Jack, C. R., Jr.;Josephs, K. A.",2015,Mar,10.1016/j.bandl.2015.01.009,0,
356,Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia,"OBJECTIVE: To use diffusion tensor imaging (DTI) to assess gray matter and white matter tract diffusion in behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SMD), and progressive nonfluent aphasia (PNFA). METHODS: This was a case-control study where 16 subjects with bvFTD, 7 with PNFA, and 4 with SMD were identified and matched by age and gender to 19 controls. All subjects had 3-T head MRI with a DTI sequence with diffusion encoding in 21 directions. Gray matter mean diffusivity (MD) was assessed using a region-of-interest (ROI) and voxel-level approach, and voxel-based morphometry was used to assess patterns of gray matter loss. White matter tract diffusivity (fractional anisotropy and radial diffusivity) was assessed by placing ROIs on tracts of interest. RESULTS: In bvFTD, increased gray matter MD and gray matter loss were identified bilaterally throughout frontal and temporal lobes, with abnormal diffusivity observed in white matter tracts that connect to these regions. In SMD, gray matter loss and increased MD were identified predominantly in the left temporal lobe, with tract abnormalities observed in the inferior longitudinal fasciculus and uncinate fasciculus. In PNFA, gray matter loss and increased MD were observed in left inferior frontal lobe, insula, and supplemental motor area, with tract abnormalities observed in the superior longitudinal fasciculus. CONCLUSIONS: The diffusivity of gray matter is increased in regions that are atrophic in frontotemporal dementia, suggesting disruption of the cytoarchitecture of remaining tissue. Furthermore, damage was identified in white matter tracts that interconnect these regions, supporting the hypothesis that these diseases involve different and specific brain networks.","Aged;Anisotropy;Atrophy/etiology/pathology/physiopathology;Brain/ pathology/physiopathology;Brain Mapping;Case-Control Studies;Diffusion;Diffusion Tensor Imaging;Disease Progression;Female;Frontal Lobe/pathology/physiopathology;Frontotemporal Dementia/ pathology/physiopathology;Frontotemporal Lobar Degeneration/ pathology/physiopathology;Functional Laterality/physiology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neural Pathways/ pathology/physiopathology;Primary Progressive Nonfluent Aphasia/ pathology/physiopathology;Severity of Illness Index;Temporal Lobe/pathology/physiopathology","Whitwell, J. L.;Avula, R.;Senjem, M. L.;Kantarci, K.;Weigand, S. D.;Samikoglu, A.;Edmonson, H. A.;Vemuri, P.;Knopman, D. S.;Boeve, B. F.;Petersen, R. C.;Josephs, K. A.;Jack, C. R., Jr.",2010,Apr 20,10.1212/WNL.0b013e3181d9edde,0,
357,Blood pressure lowering for the prevention of cognitive decline in patients with cerebrovascular disease. PROGRESS Management Committee. Perindopril Protection Against Recurrent Stroke Study,"Cerebrovascular disease and high blood pressure both appear to increase the risk of vascular dementia. PROGRESS aims to investigate whether blood pressure lowering with an angiotensin coverting enzyme inhibitor-based regimen will reduce the risk of cognitive impairment in patients with a history of stroke or transient ischaemic attack. A total of at least 6000 patients will be randomised to receive perindopril (+/- indapamide) or matching placebo(s), with treatment and follow-up scheduled to continue for at least 4 years. Substudies will investigate the effects of treatment on cognitive decline in subgroups defined by apo-E genotype and on white matter lesions assessed by magnetic resonance imaging. Final results from the study should be available in 2001.","Angiotensin-Converting Enzyme Inhibitors/ pharmacology;Antihypertensive Agents/ pharmacology;Blood Pressure/ drug effects;Cerebrovascular Disorders/ drug therapy/physiopathology/psychology;Clinical Protocols;Dementia, Vascular/physiopathology/ prevention & control;Diuretics/pharmacology;Female;Humans;Indapamide/pharmacology;Indoles/ pharmacology;Ischemic Attack, Transient/drug therapy/physiopathology/psychology;Male;Middle Aged;Perindopril","Whitlock, G.;MacMahon, S.;Anderson, C.;Neal, B.;Rodgers, A.;Chalmers, J.",1997,Jul-Aug,,0,
358,INtensive versus standard ambulatory blood pressure lowering to prevent functional DeclINe in the ElderlY (INFINITY),"Reductions in mobility and cognitive function linked to accrual of brain microvascular disease related white matter hyperintensities (WMHs) on magnetic resonance imaging can occur in older hypertensive patients in as little as 2 years. We have designed a trial evaluating 2 levels of ambulatory blood pressure (ABP) control in individuals with normal or mildly impaired mobility and cognition who have detectable cerebrovascular disease (>0.5% WMH fraction of intracranial volume) on functional outcomes. The study is a prospective randomized, open-label trial with blinded end points, in patients ages ?75 years with elevated 24-hour systolic blood pressure (BP) (145 mm Hg in the untreated state) who do not have unstable cardiovascular disease, heart failure, or stroke. The primary and key secondary outcomes in the trial are change from baseline in mobility and cognitive function and damage to brain white matter as demonstrated by accrual of WMH volume and changes in diffusion tensor imaging. Approximately 300 patients will be enrolled, and 200 randomized to 1 of 2 levels of ABP control (intensive to achieve a goal 24-hour systolic BP of ?130 mm Hg or standard to achieve a goal 24-hour systolic BP of ?145 mm Hg) for a total of 36 months using similar antihypertensive regimens. The analytical approach provides 85% power to show a clinically meaningful effect in differences in mobility accompanied by quantitative differences in WMH between treatment groups. The INFINITY trial is the first to guide antihypertensive therapy using ABP monitoring rather than clinic BP to reduce cerebrovascular disease.","Antihypertensive Agents [adverse effects] [therapeutic use];Blood Pressure [drug effects];Blood Pressure Monitoring, Ambulatory [methods];Cerebrovascular Disorders [complications] [drug therapy];Cognition Disorders [complications] [drug therapy];Double-Blind Method;Hypertension [complications] [drug therapy];Leukoencephalopathies [complications] [drug therapy];Magnetic Resonance Imaging;Mobility Limitation;Prospective Studies;Treatment Outcome;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","White, W. B.;Marfatia, R.;Schmidt, J.;Wakefield, D. B.;Kaplan, R. F.;Bohannon, R. W.;Hall, C. B.;Guttmann, C. R.;Moscufo, N.;Fellows, D.;Wolfson, L.",2013,,,0,
359,A voxel-based morphometric study of nondemented adults with Down Syndrome,"Previous structural brain imaging studies of Down Syndrome (DS) have offered important insights into the underlying morphometric aberrations associated with the condition. These previous studies have relied almost exclusively on classic region-of-interest (ROI)-based morphometry, a method in which a finite number of anatomical structures must be defined and delineated a priori. Here we use the fully automated voxel-based morphometry (VBM) approach on 19 nondemented individuals with DS and 11 age-matched controls in order to provide a full-brain assessment of DS morphology. Foci of statistically significant (P < 0.05, corrected for multiple comparisons) reductions in gray matter (GM) tissue were observed in the cerebellum, cingulate gyrus, left medial frontal lobe, right middle/superior temporal gyrus, and the left CA2/CA3 region of the hippocampus. Significant decreases in white matter (WM) tissue were noted throughout the inferior brainstem. Foci of statistically significant (P < 0.05, corrected for multiple comparisons) increases in GM tissue were observed in a superior/caudal portion of the brainstem and left parahippocampal gyrus. Significant increases in WM tissue were noted bilaterally in the parahippocampal gyrus. We also noted significant increases in cerebral spinal fluid in regions suggesting enlarged lateral ventricles in the DS group. While these results are generally consistent with prior ROI-based imaging studies of nondemented DS individuals, the present findings provide additional understanding of the three-dimensional topography of DS morphology throughout the brain. The consistency of these findings with prior imaging reports demonstrates the utility of the VBM technique for investigating the neuroanatomy of DS.","Adult;Alzheimer Disease/pathology;Brain/ pathology;Brain Stem/pathology;Cerebral Cortex/pathology;Data Interpretation, Statistical;Down Syndrome/cerebrospinal fluid/ pathology/psychology;Female;Humans;Image Processing, Computer-Assisted;Intelligence Tests;Magnetic Resonance Imaging;Male;Middle Aged","White, N. S.;Alkire, M. T.;Haier, R. J.",2003,Sep,,0,
360,Morphological and cellular aspects of the aging brain,"Contemporary technologies, including digital imaging of the brain during life and quantative microscopy (unbiased stereology) for estimating histological features postmortem, have resulted in important new knowledge about changes in the brain that accompany healthy aging, including evidence that grey matter atrophies with an anterior-posterior gradient. Neurons shrink but numbers are preserved; however, there is moderate reduction in dendritic spines and in synapses that have altered function. This is to be interpreted in the light of evidence for neurogenesis continuing into late life. White matter volume increases into maturity, but in aging there is a marked reduction due mostly to a loss of small myelinated fibres. Cell inclusions characteristic of neurodegenerative disease are commonly found postmortem in the healthy aged.",,"Wherrett, J. R.",2006,Jan,,0,
361,"Plasma vitamin C, cholesterol and homocysteine are associated with grey matter volume determined by MRI in non-demented old people","We studied 82 non-demented old people and, using MRI, derived measures of grey and white matter and intracranial volumes. Controlling for sex and intracranial volume, we related grey and white matter volumes to plasma concentrations of vitamins C, B(12), folate, homocysteine, cholesterol, triglycerides, high density and low density (LDL) lipoproteins, and to red blood cell folate and glycated haemoglobin concentrations (HbA1(c)). We found that lower grey matter volume was associated with lower plasma vitamin C and higher homocysteine, cholesterol and LDL. Lower blood cell folate was also associated with lower grey matter volume but HbA1(c) was not. These data are consistent with the putative benefits of dietary vitamin C and folate intake and the role of cholesterol in age related neurodegeneration.","Aged;Analysis of Variance;Ascorbic Acid/*blood;Cerebral Cortex/anatomy & histology/*pathology;Cholesterol/*blood;Cross-Sectional Studies;Female;Homocysteine/*blood;Humans;Longitudinal Studies;Magnetic Resonance Imaging/*methods/statistics & numerical data;Male;Nerve Fibers, Myelinated/pathology;Sex Factors","Whalley, L. J.;Staff, R. T.;Murray, A. D.;Duthie, S. J.;Collins, A. R.;Lemmon, H. A.;Starr, J. M.;Deary, I. J.",2003,May 8,,0,
362,Insights into neuroepigenetics through human histone deacetylase PET imaging,"Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer's disease and schizophrenia. Consequently, histone deacetylases (HDACs) are being aggressively pursued as therapeutic targets. However, a fundamental knowledge gap exists regarding the expression and distribution of HDACs in healthy individuals for comparison to disease states. Here, we report the first-in-human evaluation of neuroepigenetic regulation in vivo. Using positron emission tomography with [(11)C]Martinostat, an imaging probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC expression is higher in cortical gray matter than in white matter, with conserved regional distribution patterns within and between healthy individuals. Among gray matter regions, HDAC expression was lowest in the hippocampus and amygdala. Through biochemical profiling of postmortem human brain tissue, we confirmed that [(11)C]Martinostat selectively binds HDAC isoforms 1, 2, and 3, the HDAC subtypes most implicated in regulating neuroplasticity and cognitive function. In human stem cell-derived neural progenitor cells, pharmacologic-level doses of Martinostat induced changes in genes closely associated with synaptic plasticity, including BDNF (brain-derived neurotrophic factor) and SYP (synaptophysin), as well as genes implicated in neurodegeneration, including GRN (progranulin), at the transcript level, in concert with increased acetylation at both histone H3 lysine 9 and histone H4 lysine 12. This study quantifies HDAC expression in the living human brain and provides the foundation for gaining unprecedented in vivo epigenetic information in health and disease.",,"Wey, H. Y.;Gilbert, T. M.;Zurcher, N. R.;She, A.;Bhanot, A.;Taillon, B. D.;Schroeder, F. A.;Wang, C.;Haggarty, S. J.;Hooker, J. M.",2016,Aug 10,10.1126/scitranslmed.aaf7551,0,
363,Clinical evaluation of the ICD-10 criteria for vascular dementia,"The clinical feasibility of the ICD-10 criteria for subtypes of vascular dementia were examined in an investigation of 61 demented patients (74.4, SD 8.2 years) showing CT appearances of vascular lesions. Only 15 cases (24.6%) fulfilled the ICD-10 criteria of vascular dementia. Of these cases, 66.6% could adequately be classified in subtypes. The most frequent types of vascular dementia were multi-infarct dementia and subcortical vascular dementia. Our findings suggest that the ICD-10 criteria of vascular dementia are more selective than the classical 'ischaemic scales'.",aged;article;brain cortex;brain ischemia;computer assisted tomography;dementia;female;human;major clinical study;male;multiinfarct dementia,"Wetterling, T.;Kanitz, R. D.;Burgis, K. J.",1993,,,0,
364,"Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN)","BACKGROUND AND PURPOSE: Vascular dementia (VD) has been an ill-defined term thus far. Recently detailed criteria for the diagnosis of VD have been proposed (Alzheimer's Disease Diagnostic and Treatment Centers [ADDTC], 1992; Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV], 1994; International Classification of Diseases, 10th revision [ICD-10], 1992, 1993; and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS-AIREN], 1993). Until now the clinical feasibility of these diagnostic guidelines has not been evaluated. METHODS: This study aimed to compare these criteria in an unselected sample of 167 elderly patients (mean age, 72.0 +/- 9.9 years) admitted with probable dementia. RESULTS: The number of cases that could be classified as VD differed widely between the various diagnostic guidelines. According to DSM-IV criteria, 45 cases were diagnosed as VD. Twenty-one cases fulfilled the ICD-10 research criteria, but only 12 met the NINDS-AIREN criteria for VD. Twenty-three cases were classified as ischemic VD as defined by the ADDTC criteria. The concordance was very poor since only 5 cases met the criteria for VD of all diagnostic guidelines. CONCLUSIONS: Our results show that the classification according to different diagnostic guidelines yields rather distinct groups of patients. The reasons responsible for these findings are as follows: (1) different criteria for dementia, (2) limitation to ischemic VD in the ADDTC criteria, (3) no further differentiation of VD into subtypes according to CT or MRI findings (DSM-IV), and (4) the multifactorial etiopathology of VD. Major diagnostic difficulties ensue from the very frequent cases with white matter lesions, since their etiology and classification remain widely unknown.","Aged;Alzheimer Disease/diagnosis;Aphasia/diagnosis;Apraxias/diagnosis;Attention;Brain Ischemia/diagnosis;Cerebrovascular Disorders/diagnosis;Dementia, Multi-Infarct/diagnosis;Dementia, Vascular/classification/*diagnosis/etiology;Feasibility Studies;Female;Humans;Judgment;Magnetic Resonance Imaging;Male;Memory;Memory, Short-Term;Neurologic Examination;Orientation;Practice Guidelines as Topic;Thinking;Tomography, X-Ray Computed;Visual Perception","Wetterling, T.;Kanitz, R. D.;Borgis, K. J.",1996,Jan,,0,
365,The ICD-10 criteria for vascular dementia,"The World Health Organization recently introduced the new ICD-10. Chapter V ('Mental and behavioural disorders including disorders of psychological development') contains operationalized diagnostic guidelines for the classification of psychiatric disorders, i.e. the term vascular dementia is clearly defined. Furthermore, the criteria of the ICD-10 allow a differentiation of vascular dementia into subtypes (vascular dementia of acute onset, multi-infarct dementia, subcortical vascular dementia, and mixed or unspecified types). The clinical feasibility of the ICD-10 criteria for subtypes of vascular dementia is proven in an investigation of 72 demented patients (75.0 +/- 8.3 years) showing vascular lesions of the computed tomography scan. Only 18 cases (25.0%) fulfill the ICD-10 criteria for vascular dementia. 61.1% of the cases could be sufficiently classified into subtypes. These results suggest that the ICD-10 criteria for vascular dementia are rather selective.","Aged;Cerebrovascular Disorders/psychology;Cognition Disorders/diagnosis/psychology;Dementia, Vascular/*classification/*diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Psychiatric Status Rating Scales;World Health Organization","Wetterling, T.;Kanitz, R. D.;Borgis, K. J.",1994,May-Aug,,0,
366,Estimating cerebral microinfarct burden from autopsy samples,"Objective: To estimate whole-brain microinfarct burden from microinfarct counts in routine postmortem examination. Methods: We developed a simple mathematical method to estimate the total number of cerebral microinfarcts from counts obtained in the small amount of tissue routinely examined in brain autopsies. We derived estimates of total microinfarct burden from autopsy brain specimens from 648 older participants in 2 community-based clinical-pathologic cohort studies of aging and dementia. Results: Our results indicate that observing 1 or 2 microinfarcts in 9 routine neuropathologic specimens implies a maximum-likelihood estimate of 552 or 1,104 microinfarcts throughout the brain. Similar estimates were obtained when validating in larger sampled brain volumes. Conclusions: The substantial whole-brain burden of cerebral microinfarcts suggested by even a few microinfarcts on routine pathologic sampling suggests a potential mechanism by which these lesions could cause neurologic dysfunction in individuals with small-vessel disease. The estimation framework developed here may generalize to clinicopathologic correlations of other imaging-negative micropathologies. © 2013 American Academy of Neurology.",,"Westover, M. B.;Bianchi, M. T.;Yang, C.;Schneider, J. A.;Greenberg, S. M.",2013,9,,0,
367,Diffusion imaging changes in grey matter in Alzheimer's disease: a potential marker of early neurodegeneration,"Alzheimer's disease (AD) is recognized to have a long presymptomatic period, during which there is progressive accumulation of molecular pathology, followed by inexorable neuronal damage. The ability to identify presymptomatic individuals with evidence of neurodegenerative change, to stage their disease, and to track progressive changes will be important for early diagnosis and for prevention trials. Despite recent advances, particularly in magnetic resonance imaging, our ability to identify early neurodegenerative changes reliably is limited. The development of diffusion-weighted magnetic resonance imaging, which is sensitive to microstructural changes not visible with conventional volumetric techniques, has led to a number of diffusion imaging studies in AD; these have largely focused on white matter changes. However, in AD cerebral grey matter is affected very early, with pathological studies suggesting that grey matter changes predate those in white matter. In this article we review the growing number of studies that assess grey matter diffusivity changes in AD. Although use of the technique is still at a relatively early stage, results so far have been promising. Initial studies identified changes in diffusion measures in the hippocampi of patients with mild cognitive impairment, which predated macroscopic volume loss, with positive predictive value for progression to AD dementia. More recent studies have identified abnormalities in multiple neocortical areas (particularly the posterior cingulate) at various stages of disease progression. Studies of patients who carry genetic mutations predisposing to autosomal dominant familial AD have shown cortical and subcortical grey matter diffusivity changes several years before the expected onset of the first clinical symptoms. The technique is not without potential methodological difficulties, especially relating to partial volume effects, although recent advances appear to be reducing such issues. Going forward, further utilization of grey matter diffusion measurements in AD may improve our understanding with regards to the timing and nature of the earliest presymptomatic neurodegenerative changes. This imaging technique may also be useful in comparing and contrasting subtle variations in different disease subgroups, and as a sensitive outcome measure for presymptomatic clinical trials in AD and other neurodegenerative diseases.",,"Weston, P. S.;Simpson, I. J.;Ryan, N. S.;Ourselin, S.;Fox, N. C.",2015,,10.1186/s13195-015-0132-3,0,
368,Increased sensitivity to effects of normal aging and Alzheimer's disease on cortical thickness by adjustment for local variability in gray/white contrast: a multi-sample MRI study,"MRI-based estimates of cerebral morphometric properties, e.g. cortical thickness, are pivotal to studies of normal and pathological brain changes. These measures are based on automated or manual segmentation procedures, which utilize the tissue contrast between gray and white matter on T(1)-weighted MR images. Tissue contrast is unlikely to remain a constant property across groups of different age and health. An important question is therefore how the sensitivity of cortical thickness estimates is influenced by variability in WM/GM contrast. The effect of adjusting for variability in WM/GM contrast on age sensitivity of cortical thickness was tested in 1189 healthy subjects from six different samples, enabling evaluation of consistency of effects within and between sites and scanners. Further, the influence of Alzheimer's disease (AD) diagnosis on cortical thickness with and without correction for contrast was tested in an additional sample of 96 patients. In healthy controls, regional increases in the sensitivity of the cortical thickness measure to age were found after correcting for contrast. Across samples, the strongest effects were observed in frontal, lateral temporal and parietal areas. Controlling for contrast variability also increased the cortical thickness estimates' sensitivity to AD, thus replicating the finding in an independent clinical sample. The results showed increased sensitivity of cortical estimates to AD in areas earlier reported to be compromised in AD, including medial temporal, inferior and superior parietal regions. In sum, the findings indicate that adjusting for contrast can increase the sensitivity of MR morphometry to variables of interest.","Adult;Aging/ pathology;Algorithms;Alzheimer Disease/ pathology;Cerebral Cortex/ pathology;Female;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Reproducibility of Results;Sensitivity and Specificity;Young Adult","Westlye, L. T.;Walhovd, K. B.;Dale, A. M.;Espeseth, T.;Reinvang, I.;Raz, N.;Agartz, I.;Greve, D. N.;Fischl, B.;Fjell, A. M.",2009,Oct 1,10.1016/j.neuroimage.2009.05.084,0,
369,Effects of APOE on brain white matter microstructure in healthy adults,"OBJECTIVES: APOE is related to cholesterol transport and clearance and brain white matter (WM) properties involving myelin, of which cholesterol is a major component. Diffusion tensor imaging enables in vivo investigations of brain WM, and could increase our understanding of the pathways leading to Alzheimer disease. The main objective was to investigate the association between APOE and diffusion tensor imaging-derived indices of WM microstructure. METHODS: Healthy participants were assessed on a range of neuropsychological measures, genotyped, and underwent MRI. A total of 203 volunteers (aged 21.1-69.9 years, mean = 47.6, SD = 14.9) with APOE genotypes epsilon2/epsilon3 (n = 30), epsilon3/epsilon3 (n = 113), and epsilon3/epsilon4 (n = 60) were included. RESULTS: There were widespread increases in mean and radial diffusion in carriers of the epsilon3/epsilon4 alleles compared with epsilon3/epsilon3 with medium to strong effect sizes (Cohen's d = 0.77-0.79). No interactions between genotype and age were observed, indicating relatively stable differences from early adulthood. The results were independent of presence of dementia in close family. We also observed increased mean and radial diffusion and decreased fractional anisotropy in carriers of the epsilon2/epsilon3 alleles compared with epsilon3/epsilon3 carriers. No significant differences were found between epsilon2/epsilon3 and epsilon3/epsilon4. CONCLUSIONS: APOE affects microstructural properties of the brain WM from early adulthood, but the specific allelic effects do not directly reflect the associated risk of developing Alzheimer disease. The role of APOE in cholesterol transport, the high density of cholesterol in myelin, and the specific effects on radial diffusivity support a putative functional role of APOE in modulating myelin-related processes in the brain.","Adult;Age Factors;Aged;Anisotropy;Apolipoproteins E/ genetics;Brain/ anatomy & histology;Brain Mapping;Diffusion Tensor Imaging;Female;Genotype;Humans;Male;Middle Aged;Nerve Fibers, Myelinated;Neuropsychological Tests;Young Adult","Westlye, L. T.;Reinvang, I.;Rootwelt, H.;Espeseth, T.",2012,Nov 6,10.1212/WNL.0b013e3182735c9c,0,
370,"Episodic memory of APOE epsilon4 carriers is correlated with fractional anisotropy, but not cortical thickness, in the medial temporal lobe","The epsilon4 allele of apolipoprotein E (apoE, protein; APOE, gene) is the most important genetic risk factor for the development of Alzheimer's disease (AD). Cortical structures in the medial temporal lobe (MTL) are important for memory function and are affected early in AD. Both gray matter (GM) and white matter (WM) structures in the MTL have been reported to display AD related changes in healthy APOE epsilon4 carriers, but the effects are relatively small and somewhat deviating. Still, there is a lack of studies directly linking structural measures with performance on psychometric tests in epsilon4+ individuals. We hypothesized that intact WM integrity in the MTL facilitates episodic memory, and predicted a higher correlation between WM integrity and memory performance in APOE epsilon4 carriers due to a possible limiting effect of WM microstructure. In the present study of 92 healthy (MMSE>27) participants we acquired T1 3D and DTI images from a 1.5T MRI scanner, and tested the participants with California Verbal Learning Test II (CVLT-II). The study had two main aims: 1) to relate verbal memory performance to entorhinal WM (EWM) integrity in APOE epsilon4 carriers and non-carriers, and 2) to investigate APOE epsilon4 effects on EWM and EC thickness. We observed a strong, positive correlation between FA in the EWM and memory performance, which was driven solely by APOE epsilon4 carriers. These effects were significant while controlling for age, sex, EWM volume and EC thickness. Although EC thickness was significantly reduced in epsilon4 carriers, we did not find a relationship between EC thickness and memory performance. Thus, increased susceptibility of the WM structures underpinning the entorhinal-hippocampal network, offers a plausible explanation for the earlier onset of cognitive decline previously reported in APOE epsilon4 carriers.","Aged;Aged, 80 and over;Apolipoprotein E4/ genetics;Female;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Memory, Episodic;Middle Aged;Organ Size;Temporal Lobe/ anatomy & histology/ physiology","Westlye, E. T.;Hodneland, E.;Haasz, J.;Espeseth, T.;Lundervold, A.;Lundervold, A. J.",2012,Oct 15,10.1016/j.neuroimage.2012.06.072,0,
371,Novel whole brain segmentation and volume estimation using quantitative MRI,"OBJECTIVES: Brain segmentation and volume estimation of grey matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) are important for many neurological applications. Volumetric changes are observed in multiple sclerosis (MS), Alzheimer's disease and dementia, and in normal aging. A novel method is presented to segment brain tissue based on quantitative magnetic resonance imaging (qMRI) of the longitudinal relaxation rate R(1), the transverse relaxation rate R(2) and the proton density, PD. METHODS: Previously reported qMRI values for WM, GM and CSF were used to define tissues and a Bloch simulation performed to investigate R(1), R(2) and PD for tissue mixtures in the presence of noise. Based on the simulations a lookup grid was constructed to relate tissue partial volume to the R(1)-R(2)-PD space. The method was validated in 10 healthy subjects. MRI data were acquired using six resolutions and three geometries. RESULTS: Repeatability for different resolutions was 3.2% for WM, 3.2% for GM, 1.0% for CSF and 2.2% for total brain volume. Repeatability for different geometries was 8.5% for WM, 9.4% for GM, 2.4% for CSF and 2.4% for total brain volume. CONCLUSION: We propose a new robust qMRI-based approach which we demonstrate in a patient with MS. KEY POINTS: * A method for segmenting the brain and estimating tissue volume is presented * This method measures white matter, grey matter, cerebrospinal fluid and remaining tissue * The method calculates tissue fractions in voxel, thus accounting for partial volume * Repeatability was 2.2% for total brain volume with imaging resolution <2.0 mm.","Adult;Algorithms;Brain/ anatomy & histology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Young Adult","West, J.;Warntjes, J. B.;Lundberg, P.",2012,May,10.1007/s00330-011-2336-7,0,
372,Integrity of cerebral white matter in type 1 diabetes,,brain size;cognition;cognitive defect;dementia;disease activity;disease association;gray matter;human;insulin dependent diabetes mellitus;letter;neurologic disease;neuropsychological test;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident;white matter,"Wessels, A. M.",2008,,,0,
373,"Mitochondrial encephalomyopathy: Clinical pattern, CT-morphology, neuropathology","Basing on the example of two cases, the clinical and morphological variability of mitochondrial encephalomyopathies is demonstrated. Both patients were of short build, and the clinical signs and symptoms were dementia, ataxia, epilepsy and hardness of hearing, whereas signs of myopathy were very mild or absent. Computed tomography showed infratentorial pronounced atrophy of the brain and basal ganglia calcifications, in one case additionally ischemic infarctions, as can be seen in 'mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome' (MELAS). A CT follow-up over 8 years with a progression of the abnormalities parallel to the progressive clinical course is demonstrated. Besides typical 'ragged red fibres-myopathy' different abnormalities of mitochondria were seen by the electron microscope. One of the patients died; he had exceptional pathological anatomical findings with mitochondrial cardiomyopathy, angioma and necrotising encephalopathy of Leigh's type. The two case reports show that in patients with such multisystemic neurological signs and CT-findings mitochondrial encephalomyopathy should be considered and a muscle biopsy should be performed.",adult;autopsy;brain disease;case report;clinical feature;computer analysis;computer assisted tomography;diagnosis;electroencephalography;evoked response;fatality;histology;human;hyperlactatemia;male;mitochondrial myopathy;muscle biopsy;prognosis;short survey;cerebrovascular accident;ultrastructure,"Wessel, K.;Poremba, M.;Pfeiffer, J.;Roggendorf, W.",1988,,,0,
374,Impaired and preserved aspects of feedback learning in aMCI: contributions of structural connectivity,"Distinct lines of research demonstrated that patients with amnestic mild cognitive impairment (aMCI), a potential precursor of Alzheimer disease (AD), are particularly impaired in remembering relations between items and that the use of emotional targets can facilitate memory in patients with AD. We link these findings by examining learning through positive and negative feedback in patients with aMCI, and explore its anatomic underpinnings with diffusion tensor imaging and tractography. Compared to healthy controls, patients with single-domain aMCI were impaired in learning from positive feedback, while learning from negative outcomes was preserved. Among pathways within the brain circuit involved in feedback learning, abnormal white matter microstructure was observed in tracts, which connect left-hemispheric amygdala with hippocampus and entorhinal cortex. In all participants, reduced white matter integrity in this left fiber tract was specifically associated with learning from positive outcomes. Microstructure of right-hemispheric tracts between amygdala and entorhinal cortex was related to learning from negative feedback, and was not compromised in aMCI patients. Our results provide new insight into how anatomical connections might contribute to impaired and preserved aspects of learning behaviors in the early AD process and indicate potential compensatory mechanisms.",Aged;Amnesia/complications/ pathology/ psychology;Amygdala/pathology;Brain/ pathology;Cognitive Dysfunction/complications/ pathology/ psychology;Diffusion Tensor Imaging;Entorhinal Cortex/pathology;Female;Formative Feedback;Functional Laterality;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology;White Matter/ pathology;Amnestic mild cognitive impairment;Amygdala;Entorhinal cortex;Hippocampus;Tractography,"Wessa, M.;King, A. V.;Meyer, P.;Frolich, L.;Flor, H.;Poupon, C.;Hoppstadter, M.;Linke, J.",2016,Jun,,0,375
375,Impaired and preserved aspects of feedback learning in aMCI: contributions of structural connectivity,"Distinct lines of research demonstrated that patients with amnestic mild cognitive impairment (aMCI), a potential precursor of Alzheimer disease (AD), are particularly impaired in remembering relations between items and that the use of emotional targets can facilitate memory in patients with AD. We link these findings by examining learning through positive and negative feedback in patients with aMCI, and explore its anatomic underpinnings with diffusion tensor imaging and tractography. Compared to healthy controls, patients with single-domain aMCI were impaired in learning from positive feedback, while learning from negative outcomes was preserved. Among pathways within the brain circuit involved in feedback learning, abnormal white matter microstructure was observed in tracts, which connect left-hemispheric amygdala with hippocampus and entorhinal cortex. In all participants, reduced white matter integrity in this left fiber tract was specifically associated with learning from positive outcomes. Microstructure of right-hemispheric tracts between amygdala and entorhinal cortex was related to learning from negative feedback, and was not compromised in aMCI patients. Our results provide new insight into how anatomical connections might contribute to impaired and preserved aspects of learning behaviors in the early AD process and indicate potential compensatory mechanisms.",,"Wessa, M.;King, A. V.;Meyer, P.;Frolich, L.;Flor, H.;Poupon, C.;Hoppstadter, M.;Linke, J.",2015,Jun 18,10.1007/s00429-015-1075-y,0,
376,Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function,"OBJECTIVE: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). METHODS: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. RESULTS: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (beta = -0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (beta = -0.237, p < 0.001), as well as regional FA scores of the frontal lobes (beta = -0.246, p < 0.001), the corona radiata (beta = -0.222, p < 0.001), and the corpus callosum (beta = -0.141, p = 0.016), in particular the genu (beta = -0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. CONCLUSION: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.","Aging;Anisotropy;Brain/ anatomy & histology/immunology;C-Reactive Protein/ metabolism;Cerebrovascular Disorders/immunology/pathology;Cognition;Cohort Studies;Cross-Sectional Studies;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated;Neural Pathways/anatomy & histology/immunology;Neuropsychological Tests;Psychometrics;Regression Analysis","Wersching, H.;Duning, T.;Lohmann, H.;Mohammadi, S.;Stehling, C.;Fobker, M.;Conty, M.;Minnerup, J.;Ringelstein, E. B.;Berger, K.;Deppe, M.;Knecht, S.",2010,Mar 30,10.1212/WNL.0b013e3181d7b45b,0,
377,The growing clinical spectrum of cerebral amyloid angiopathy,"PURPOSE OF REVIEW: Cerebral amyloid angiopathy (CAA) is diagnosed primarily as a cause of lobar intracerebral hemorrhages (ICH) in elderly patients. With improving MRI techniques, however, the role of CAA in causing other symptoms has become clear. Recognizing the full clinical spectrum of CAA is important for diagnosis and treatment. In this review we summarize recent insights in clinical CAA features, MRI biomarkers, and management. RECENT FINDINGS: The rate of ICH recurrence in CAA is among the highest of all stroke subtypes. Cortical superficial siderosis (cSS) and cortical subarachnoid hemorrhage (cSAH) are important imaging predictors for recurrent ICH. CAA also causes cognitive problems in multiple domains. In patients with nondemented CAA, the risk of developing dementia is high especially after ICH. CAA pathology probably starts years before the first clinical manifestations. The first signs in hereditary CAA are white matter lesions, cortical microinfarcts, and impaired occipital cerebral vasoreactivity. Visible centrum semiovale perivascular spaces, lobar located lacunes, and cortical atrophy are new nonhemorrhagic MRI markers. SUMMARY: CAA should be in the differential diagnosis of elderly patients with lobar ICH but also in those with cognitive decline and episodic transient neurological symptoms. Physicians should be aware of the cognitive effects of CAA. In patients with a previous ICH, cSS, or cSAH, anticoagulation should be considered risky. The increasing number of MRI markers may help to discriminate CAA from other small vessel diseases and dementia subtypes.",,"Wermer, M. J. H.;Greenberg, S. M.",2018,Feb,,0,
378,Musical hallucinations. The sounds of silence?,"Hallucinations may occur in any sensory modality. Auditory hallucinations, usually ascribed to psychiatric illness, take various forms including the perception of voices, cries, noises, or rarely, music. Formed musical hallucinations, (ie, the perception of either vocal or instrumental melodies), reported in the English literature to date have typically been associated with marked hearing loss, advanced age (average 67.8 years), female sex (71%), lack of response to treatment, and general lack of associated psychopathology. We have collected data on seven additional patients with musical hallucinations. The average age of these patients was 72.9 years; all were women. Six had significant hearing problems. All reported onset of musical hallucinations after the age of 60. Interestingly, all seven had major psychiatric illnesses. Four had major depression, two had late-onset schizophrenia, and one had multi-infarct dementia. Of the five who had CT scans, one was normal and the rest demonstrated varying degrees of brain pathology. Neuroleptics were used with varying results in three cases; antidepressants were used in two depressed patients and were temporally related to the onset of musical hallucinations in one patient. Electroconvulsive therapy (ECT) was very effective in treating depression and musical hallucinations in the three patients for whom it was used, usually providing relief from hallucinations after only two treatments. Our collection of cases demonstrates that musical hallucinations can occur in association with psychiatric illness, and perhaps unlike the hallucinations associated with isolated hearing loss, may respond to conventional treatments for the underlying psychiatric disorder. Hearing loss is neither a necessary nor sufficient condition for the occurrence of musical hallucinations.","Aged;Aged, 80 and over;Antidepressive Agents/therapeutic use;Antipsychotic Agents/therapeutic use;Deafness/complications;Depression/complications;Electroconvulsive Therapy;Female;Hallucinations/*complications/therapy;Humans;Middle Aged;*Music;Psychotic Disorders/*complications","Wengel, S. P.;Burke, W. J.;Holemon, D.",1989,Feb,,0,
379,"ApoE ϵ4 is associated with cognition, brain integrity, and atrophy in HIV Over Age 60","Background: There are contradicting reports on the associations between Apolipoprotein E4 (ApoE ϵ4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups. Methods: We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging. Results: The median age of the participants was 64 years (range: 60-84) and the median estimated duration of HIV infection was 22 years. Apo ϵ4 carriers (n 19) were similar to noncarriers (n 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ϵ4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ϵ4 carriers compared with ϵ4 noncarriers. Conclusions: In this sample of older HIV-infected individuals, having at least 1 ApoE ϵ4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.",apolipoprotein E4;genomic DNA;virus RNA;adult;age;aged;article;brain atrophy;brain size;brain stem;CD4 lymphocyte count;cognition;controlled study;corpus callosum;cross-sectional study;diffusion tensor imaging;disease duration;executive function;female;genetic association;genotype;human;Human immunodeficiency virus infection;major clinical study;male;morphometrics;nuclear magnetic resonance imaging;priority journal;sex difference;thalamus;white matter,"Wendelken, L. A.;Jahanshad, N.;Rosen, H. J.;Busovaca, E.;Allen, I.;Coppola, G.;Adams, C.;Rankin, K. P.;Milanini, B.;Clifford, K.;Wojta, K.;Nir, T. M.;Gutman, B. A.;Thompson, P. M.;Valcour, V.",2016,,10.1097/qai.0000000000001091,0,
380,The value of CT in diagnosis and prognosis of different inborn neurodegenerative disorders in childhood,"Inborn errors of metabolism in 40 children have been investigated by computer tomography to obtain data on the degree of cerebral involvement in neurodegenerative and storage disorders: 20 children had various mucopolysaccharidoses, 8 sphingolipidoses, 3 mucolipidoses, 2 oligosaccharidoses, 3 cereoidlipofuscinoses and 4 had various leucodystrophies. Diagnosis in all patients except Alexander's disease was established by biochemical or histological means. The main findings on CT were cerebral atrophy with enlargement of the ventricles and the subarachnoid spaces and hypodensity of the white matter. The degree of cerebral atrophy seemed to develop according to the age of the patients, as could be seen from the patients with mucopolysaccharidosis III, metachromatic leucodystrophy and GM1-gangliosidosis. Hypodensity of the white matter was found in mucopolysaccharidosis I-H, II-B, VI, in mucolipidosis II and in patients with leucodystrophies. On the other hand, there was great variability in these CT findings even in siblings, as seen in four patients with mucopolysaccharidosis VI. Among the series there were several patients who did not show any abnormalities in CT, so that a negative CT did not exclude these disorders, even the leucodystrophies. CT features such as cerebral atrophy or hypodensity were helpful in the evaluation of these disorders, though a diagnosis could not be made by CT alone.",brain atrophy;central nervous system;child;computer analysis;computer assisted tomography;congenital disorder;diagnosis;heredity;human;inborn error of metabolism;lipidosis;major clinical study;mental deficiency;mucolipidosis;mucopolysaccharidosis;nerve cell degeneration;nervous system;neuronal ceroid lipofuscinosis;oligosaccharidosis,"Wende, S.;Ludwig, B.;Kishikawa, T.",1984,,,0,
381,Microstructural network alterations of olfactory dysfunction in newly diagnosed Parkinson's disease,"Olfactory dysfunction is a robust and early sign for Parkinson's disease (PD). Previous studies have revealed its association with dementia and related neural changes in PD. Yet, how olfactory dysfunction affects white matter (WM) microstructure in newly diagnosed and untreated PD remains unclear. Here we comprehensively examined WM features using unbiased whole-brain analyses. 88 newly diagnosed PD patients without dementia (70 with hyposmia and 18 without hyposmia) and 33 healthy controls underwent clinical assessment and diffusion tensor imaging (DTI) scanning. Tract-based special statistics (TBSS), graph-theoretic methods and network-based statistics (NBS) were used to compare regional and network-related WM features between groups. TBSS analysis did not show any differences in fractional anisotropy and mean diffusivity between groups. Compared with controls, PD patients without hyposmia showed a significant decrease in global efficiency, whilst PD patients with hyposmia exhibited significantly reduced global and local efficiency and additionally a disrupted connection between the right medial orbitofrontal cortex and left rectus and had poorer frontal-related cognitive functioning. These results demonstrate that hyposmia-related WM changes in early PD only occur at the network level. The confined disconnectivity between the bilateral olfactory circuitry may serve as a biomarker for olfactory dysfunction in early PD.",,"Wen, M. C.;Xu, Z.;Lu, Z.;Chan, L. L.;Tan, E. K.;Tan, L. C. S.",2017,Oct 2,,0,
382,Structural connectome alterations in prodromal and de novo Parkinson's disease patients,"BACKGROUND: Although the clinical signs of prodromal Parkinson's disease (PD) have been identified, little is known about the neural features of the prodromal phase of PD (proPD). The aim of this study was to examine the structural network alterations from healthy aging to proPD and to early PD. METHODS: 181 non-demented and non-depressed participants comprising 55 healthy controls (HCs), 20 proPDs, and 106 de novo PD patients (dPDs) were included in the study and underwent clinical assessment and diffusion tensor imaging scanning. Graph-theoretical analysis and network-based statistics, with age and gender as nuisance covariates, were used. RESULTS: Compared with HCs and dPDs, proPD patients showed significantly elevated small-worldness and clustering coefficient (Ps < 0.01) and greater local connectivity between regions relating to motor, olfactory and sleep functions (Ps < 0.05). Although dPDs and HCs did not differ on all graph-theoretic metrics, dPD patients showed decreased connectivity within the prefrontal regions and between the left temporal and occipital lobes (P < 0.05). The connectivity strength between these regions significantly distinguished between diagnostic groups. Connectivity between bilateral SMAs was correlated with UPSIT in HCs and with UPDRS-III in dPDs. Connectivity between the right SMA and putamen was correlated RBDSQ in proPDs. CONCLUSIONS: Increased network efficiency and connectivity of proPDs and decreased local connectivity of dPDs might suggest the emergence and dissipation of neural compensation in the prodromal phase and in early PD, respectively. Nonetheless, longitudinal studies are needed to follow up the long-term structural network changes of proPD patients.",Neuroimaging;Olfactory impairment;Parkinson's disease;Prodromal phase;Sleep;White matter,"Wen, M. C.;Heng, H. S. E.;Hsu, J. L.;Xu, Z.;Liew, G. M.;Au, W. L.;Chan, L. L.;Tan, L. C. S.;Tan, E. K.",2017,Dec,,0,
383,Effect of white matter changes on cognitive impairment in patients with lacunar infarcts,"BACKGROUND AND PURPOSE: Cerebral white matter changes (WMC) and lacunar infarct are both believed to be consequence of small vessel disease. Whether the extent of WMC affect the type and degree of cognitive impairment in patients with lacunar infarct is not clear. The study was undertaken to determine if WMC influences cognition in patients with lacunar infarcts. METHODS: We recruited consecutive patients who were admitted to the acute stroke unit because of acute lacunar infarcts, mainly documented by diffusion-weighted magnetic resonance imaging. WMC were measured qualitatively and quantitatively. Patients were divided into quartiles according to the distribution of the volume of WMC. Cognition was assessed 12 weeks after stroke by psychometric tests (Chinese version of Mini-Mental State Examination [MMSE], Alzheimer's Disease Assessment Scale-cognition [ADAS-cog], Mattis Dementia Rating Scale-Initiation/ Perseveration subscale [MDRS I/P]) and was compared between patients with varying severity of WMC. Multivariate linear regression analysis was performed to find variables that influenced performance in the psychometric tests. RESULTS: Among the 94 included patients with acute lacunar infarcts, those patients (n=25) within the highest quartile of WMC were older, had more lacunar infarcts, more severe stroke, and lower prestroke cognitive function compared with those with less WMC. In addition, their performances in psychometric tests were significantly more impaired. Multivariate linear regression analysis revealed that WMC significantly influenced performance in MDRS I/P. WMC did not independently influence performance in MMSE and ADAS-cog. CONCLUSIONS: Extent of WMC appears to be associated with executive dysfunction in stroke patients with lacunar infarcts. Further large prospective studies with extensive scales of executive function testing are required to confirm this issue.","Aged;Brain/pathology;Brain Infarction/ complications/diagnosis/ pathology;Cognition Disorders/ etiology;Diffusion Magnetic Resonance Imaging;Female;Humans;Leukoaraiosis/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Wen, H. M.;Mok, V. C.;Fan, Y. H.;Lam, W. W.;Tang, W. K.;Wong, A.;Huang, R. X.;Wong, K. S.",2004,Aug,10.1161/01.str.0000133686.29320.58,0,
384,Apolipoprotein E epsilon4 allele is associated with the volume of white matter changes in patients with lacunar infarcts,"The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and white matter changes (WMC) in elderly subjects or patients with Alzheimer's disease is controversial. To investigate this polymorphism in relation to WMC in patients with lacunar infarcts, we prospectively observed 67 patients with acute lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined using a nested polymerase chain reaction. WMC were measured quantitatively and were divided into two groups, severe and mild, with the mean volume of WMC as the cut point. Twenty-two patients (33%) had severe WMC. There was a significant difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P = 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients with lacunar infarcts. Further studies are required to confirm this finding.","Aged;Aged, 80 and over;*Alleles;Apolipoprotein E2;Apolipoprotein E3;Apolipoprotein E4;Apolipoproteins E/*genetics;Brain/*pathology;Brain Infarction/*diagnosis/*genetics;Case-Control Studies;Female;Gene Frequency;Genotype;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Polymerase Chain Reaction;Prospective Studies;Severity of Illness Index","Wen, H. M.;Baum, L.;Cheung, W. S.;Mok, V.;Lam, W. W.;Tomlinson, B.;Wong, K. S.;Ng, H. K.",2006,Nov,10.1111/j.1468-1331.2006.01436.x,0,
385,[Cranial magnetic resonance tomography--value in diagnosis of dementia. Important additional information for differential diagnosis] Kraniale Magnetresonanztomographie-Stellenwert in der Demenzdiagnostik. Wichtige Zusatzinformationen fur die Differentialdiagnose,"The clinical data and the magnetic resonance imaging (MRI) findings of 41 patients with clinically diagnosed dementia of the Alzheimer type (DAT) and 20 age-matched healthy controls were evaluated with the aim of determining the value of MRI in the diagnosis and differential diagnosis of dementia. Patients and controls with cerebrovascular risk factors, including a history of stroke, were excluded from the analysis. The MRI findings of patients with dementia revealed pathological changes, in particular cerebral atrophy (p < 0.0005), significantly more frequently than did those of controls (p < 0.005). Periventricular demyelinisation and lesions of the white matter were found in 23 (56%) patients, and in 6 (30%) of the controls. MRI revealed one case each of subdural hematoma, hydrocephalus and cerebral amyloid angiopathy. In 14 patients, the detection MRI scans of cerebral infarctions or hematomas suggested a major vascular component of the dementia. In contrast, lesions of the white matter can not reliably by ascribed to a vascular etiology. On the basis of our findings, it is concluded that cranial MRI is of great value for the differential diagnosis of dementia, even when the clinical diagnosis of Alzheimer's dementia is probable and cerebrovascular risk factors are absent.","Aged;Alzheimer Disease/ diagnosis;Brain/pathology;Dementia, Vascular/diagnosis;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule","Welter, F.;Buttner, T.;Schumacher, S.;Mariss, G.",1996,Nov 30,,0,
386,Cranial magnetic resonance tomography--value in diagnosis of dementia. Important additional information for differential diagnosis,"The clinical data and the magnetic resonance imaging (MRI) findings of 41 patients with clinically diagnosed dementia of the Alzheimer type (DAT) and 20 age-matched healthy controls were evaluated with the aim of determining the value of MRI in the diagnosis and differential diagnosis of dementia. Patients and controls with cerebrovascular risk factors, including a history of stroke, were excluded from the analysis. The MRI findings of patients with dementia revealed pathological changes, in particular cerebral atrophy (p < 0.0005), significantly more frequently than did those of controls (p < 0.005). Periventricular demyelinisation and lesions of the white matter were found in 23 (56%) patients, and in 6 (30%) of the controls. MRI revealed one case each of subdural hematoma, hydrocephalus and cerebral amyloid angiopathy. In 14 patients, the detection MRI scans of cerebral infarctions or hematomas suggested a major vascular component of the dementia. In contrast, lesions of the white matter can not reliably by ascribed to a vascular etiology. On the basis of our findings, it is concluded that cranial MRI is of great value for the differential diagnosis of dementia, even when the clinical diagnosis of Alzheimer's dementia is probable and cerebrovascular risk factors are absent.","Aged;Alzheimer Disease/ diagnosis;Brain/pathology;Dementia, Vascular/diagnosis;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule","Welter, F.;Buttner, T.;Schumacher, S.;Mariss, G.",1996,Nov 30,,0,
387,Thalamic infarct presenting as catastrophic life-threatening event in an older adult,"An 84 year old woman with history of moderate Alzheimer's disease, depression, and an anxiety disorder presented to our emergency room at Victoria Hospital, London, Ontario in an 'unresponsive' state. The patient was akinetic with mutism, and clonic perseveration induced in the upper limbs was evident while she was examined. Heart attack, massive stroke, or intracranial bleed were ruled out, and an electroencephalogram showed no epileptiform activity. Despite a normal CT, a magnetic resonance scan was ordered and showed bilateral acute paramedian thalamogeniculate infarction arising from occlusion of the artery of Percheron. Bilateral thalamic infarcts can cause sudden onset of akinetic mutism with clonic perseveration, which may be confused with coma and seizures due to life threatening conditions such as a massive stroke. Thorough clinical assessment and early use of MRI scanning will assist physicians with a more accurate diagnosis of older adults with this kind of presentation. ©2011, Editrice Kurtis.",aged;akinesia;Alzheimer disease;anxiety disorder;article;brain hemorrhage;brain infarction;case report;clonus;coma;computer assisted tomography;depression;diagnostic accuracy;disease severity;electroencephalogram;emergency ward;female;human;mutism;nuclear magnetic resonance imaging;cerebrovascular accident;thalamus,"Wells, M.;Jacques, R.;Odasso, M. M.",2011,,,0,
388,In vivo imaging of tau pathology using multi-parametric quantitative MRI,"As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.","Alzheimer Disease/diagnosis;Animals;Biomarkers;Disease Models, Animal;Female;Magnetic Resonance Imaging/ methods;Mice;Mice, Transgenic;Tauopathies/ diagnosis;tau Proteins/ metabolism","Wells, J. A.;O'Callaghan, J. M.;Holmes, H. E.;Powell, N. M.;Johnson, R. A.;Siow, B.;Torrealdea, F.;Ismail, O.;Walker-Samuel, S.;Golay, X.;Rega, M.;Richardson, S.;Modat, M.;Cardoso, M. J.;Ourselin, S.;Schwarz, A. J.;Ahmed, Z.;Murray, T. K.;O'Neill, M. J.;Collins, E. C.;Colgan, N.;Lythgoe, M. F.",2015,May 1,10.1016/j.neuroimage.2015.02.023,0,
389,Neurodegeneration across stages of cognitive decline in Parkinson disease,"OBJECTIVE: To assess regions and patterns of brain atrophy in patients with Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia-level cognitive deficits (PDD). DESIGN: Images were quantified using a region-of-interest approach and voxel-based morphometry analysis. We used a high-dimensional pattern classification approach to delineate brain regions that collectively formed the Spatial Pattern of Abnormalities for Recognition of PDD. SETTING: The Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania. SUBJECTS: Eighty-four PD patients (61 PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent magnetic resonance imaging of the brain. RESULTS: The PD-NC patients did not demonstrate significant brain atrophy compared with HCs. Compared with PD-NC patients, PD-MCI patients had hippocampal atrophy (beta = -0.37; P = .001), and PDD patients demonstrated hippocampal (beta = -0.32; P = .004) and additional medial temporal lobe atrophy (beta = -0.36; P = .003). The PD-MCI patients had a different pattern of atrophy compared with PD-NC patients (P = .04) and a similar pattern to that of PDD patients (P = .81), characterized by hippocampal, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter atrophy. In nondemented PD patients, there was a correlation between memory-encoding performance and hippocampal volume. CONCLUSIONS: Hippocampal atrophy is a biomarker of initial cognitive decline in PD, including impaired memory encoding and storage, suggesting heterogeneity in the neural substrate of memory impairment. Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline.","Aged;Biomarkers;Cognition Disorders/classification/diagnosis;Female;Humans;Image Processing, Computer-Assisted/methods;Male;Mild Cognitive Impairment/pathology/psychology;Neurodegenerative Diseases/ diagnosis;Neuropsychological Tests;Parkinson Disease/ diagnosis/pathology/psychology","Weintraub, D.;Doshi, J.;Koka, D.;Davatzikos, C.;Siderowf, A. D.;Duda, J. E.;Wolk, D. A.;Moberg, P. J.;Xie, S. X.;Clark, C. M.",2011,Dec,10.1001/archneurol.2011.725,0,
390,SPECT in the diagnosis of Alzheimer's disease and multi-infarct-dementia,"SPECT with Tc-99m HM-PAO as a radiopharmaceutical was performed in 17 patients meeting research criteria for Alzheimer's disease (AD), in 10 patients with a clinical diagnosis of multi-infarct-dementia (MID) and in 12 healthy volunteers. Regional tracer uptake was measured in frontal, parietal, and temporoparietal regions. A statistically significant decrease of tracer uptake in the temporoparietal region was found in AD-patients compared with controls. AD-patients showed less activity in this region than MID-patients, but this difference did not reach statistical significance. In both AD- and MID-patients decrease of tracer uptake was not correlated with dementia severity. We conclude that SPECT brain imaging is not yet ready for routine use in the distinction between AD and MID.","Aged;Aged, 80 and over;Alzheimer Disease/ radionuclide imaging;Analysis of Variance;Brain/ radionuclide imaging;Dementia, Multi-Infarct/ radionuclide imaging;Female;Humans;Male;Organotechnetium Compounds;Oximes;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/ methods","Weinstein, H. C.;Haan, J.;van Royen, E. O.;Derix, M. M.;Lanser, J. B.;van der Zant, F.;Dunnewold, R. J.;van Kroonenburgh, M. J.;Pauwels, E. K.;van der Velde, E. A.;et al.",1991,,,0,
391,Association of Nonalcoholic Fatty Liver Disease With Lower Brain Volume in Healthy Middle-aged Adults in the Framingham Study,"Importance: Nonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans. Objective: To assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures. Design, Setting, and Participants: The cross-sectional association between NAFLD and brain MRI measures was assessed from November 6, 2002, to March 16, 2011, in 766 individuals from the Offspring cohort of the Framingham Study. Participants were included if they did not have excessive alcohol intake and were free of stroke and dementia. Data analysis was conducted from December 30, 2015, to June 15, 2016. Exposures: Nonalcoholic fatty liver disease was assessed by multidetector computed tomographic scans of the abdomen. Main Outcomes and Measures: Linear or logistic regression models were used to evaluate the cross-sectional association between NAFLD and brain MRI measures, adjusting for age, sex, alcohol consumption, visceral adipose tissue, body mass index, menopausal status, systolic blood pressure, hypertension, current smoking, high-density lipoprotein and low-density lipoprotein cholesterol levels, lipid treatment, type 2 diabetes, cardiovascular disease, physical activity, insulin resistance, C-reactive protein levels, and plasma homocysteine values. Brain MRI measures included total cerebral brain volume, hippocampal and white matter hyperintensity volumes, and presence or absence of covert brain infarcts. Results: Of the 766 individuals in the study sample (410 women and 356 men; mean [SD] age at the time of brain MRI, 67 [9] years), 137 (17.9%) had NAFLD. Nonalcoholic fatty liver disease was significantly associated with smaller total cerebral brain volume even after adjustment for all the covariates included in the study (beta [SE], -0.26 [0.11]; P = .02). Differences in total cerebral brain volume between those with and without NAFLD corresponded to 4.2 years of brain aging in the general sample and to 7.3 years in individuals younger than 60 years of age. No statistically significant associations were observed between NAFLD and hippocampal or white matter hyperintensity volumes or covert brain infarcts. Conclusions and Relevance: Nonalcoholic fatty liver disease is associated with a smaller total cerebral brain volume, independent of visceral adipose tissue and cardiometabolic risk factors, pointing to a possible link between hepatic steatosis and brain aging.",,"Weinstein, G.;Zelber-Sagi, S.;Preis, S. R.;Beiser, A. S.;DeCarli, C.;Speliotes, E. K.;Satizabal, C. L.;Vasan, R. S.;Seshadri, S.",2018,Jan 1,,0,
392,"Risk estimations, risk factors, and genetic variants associated with alzheimer's disease in selected publications from the framingham heart study","The study of Alzheimer's disease (AD) in the Framingham Heart Study (FHS), a multi-generational, community-based population study, began nearly four decades ago. In this overview, we highlight findings from seven prior publications that examined lifetime risk estimates for AD, environmental risk factors for AD, circulating and imaging markers of aging-related brain injury, and explorations on the genetics underlying AD. First, we describe estimations of the lifetime risk of AD. These estimates are distinguished from other measures of disease burden and have substantial public health implications. We then describe prospective studies of environmental AD risk factors: one examined the association between plasma levels of omega-3 fatty-acid and risk of incident AD, the other explored the association of diabetes to this risk in subsamples with specific characteristics. With evidence of inflammation as an underlying mechanism, we also describe findings from a study that compared the effects of serum cytokines and spontaneous production of peripheral blood mononuclear cell cytokines on AD risk. Investigating AD related endophenotypes increases sensitivity in identifying risk factors and can be used to explore pathophysiologic pathways between a risk factor and the disease. We describe findings of an association between large volume of white matter hyperintensities and a specific pattern of cognitive deficits in non-demented participants. Finally, we summarize our findings from two genetic studies: The first used genome-wide association (GWA) and family-based association methods to explore the genetic basis of cognitive and structural brain traits. The second is a large meta-analysis GWA study of AD, in which novel loci of AD susceptibility were found. Together, these findings demonstrate the FHS multi-directional efforts in investigating dementia and AD. © 2013 The authors and IOS Press. All rights reserved.",,"Weinstein, G.;Wolf, P. A.;Beiser, A. S.;Au, R.;Seshadri, S.",2012,2012,,0,
393,Glucose indices are associated with cognitive and structural brain measures in young adults,"OBJECTIVE: To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults. METHODS: The sample included dementia-free participants (mean age 40 +/- 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested. RESULTS: Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses. CONCLUSIONS: We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.",Adult;Aged;Blood Glucose/metabolism;*Brain Diseases/etiology/pathology/physiopathology;*Cognition Disorders/etiology/pathology/physiopathology;*Diabetes Complications/blood/pathology/physiopathology;Diabetes Mellitus/*blood;Female;Gray Matter/pathology;Humans;Insulin Resistance/physiology;Male;Middle Aged;White Matter/pathology;Young Adult,"Weinstein, G.;Maillard, P.;Himali, J. J.;Beiser, A. S.;Au, R.;Wolf, P. A.;Seshadri, S.;DeCarli, C.",2015,Jun 9,10.1212/wnl.0000000000001655,0,
394,Association of parental stroke with brain injury and cognitive measures in offspring: The Framingham heart study,"Background and Purpose-Parental stroke has been related to an increased risk of stroke in the offspring. This study examines whether parental stroke is also associated with increased vascular brain injury and poorer cognitive performance among offspring free of clinical stroke. Methods-Multivariable regression analyses were used to relate parental stroke to cross-sectional and change in brain magnetic resonance imaging measures and cognitive function among the offspring, with and without adjustment for vascular risk factors. Results-Stroke- and dementia-free Framingham Offspring (n=1297, age, 61±9 years, 54% women) were studied. Parental stroke by age 65 years was associated with a higher baseline white matter hyperintensity volume (β=0.17±0. 08; P=0.027) and with lower visual memory performance (β= -0.80±0.34; P=0.017). During a 6-year follow-up, parental stroke was also associated with increase in white matter hyperintensity volume (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.03- 3.38) and decline in executive function (Trails B-A; OR, 1.81; 95% CI, 1.06-3.09). The associations with white matter hyperintensity volume and visual memory attenuated after additional adjustment for concomitant vascular risk factors. Conclusions-Parental stroke by age 65 years is associated with increased vascular brain injury and lower memory in offspring equivalent to 3 and 7 years of brain aging, respectively. This may be partly attributed to inheritance of vascular risk factors. © 2013 American Heart Association, Inc.",,"Weinstein, G.;Beiser, A. S.;Au, R.;De Carli, C.;Wolf, P. A.;Seshadri, S.",2013,March,,0,
395,Endothelial depletion of murine SRF/MRTF provokes intracerebral hemorrhagic stroke,"Intracerebral hemorrhagic stroke and vascular dementia are age- and hypertension-associated manifestations of human cerebral small vessel disease (SVD). Cerebral microvessels are formed by endothelial cells (ECs), which are connected through tight junctions, adherens junctions, and stabilizing basement membrane structures. These endothelial connections ensure both vessel stability and blood-brain barrier (BBB) functions, the latter enabling selective exchange of ions, bioactive molecules, and cells between the bloodstream and brain tissue. Srf(iECKO) mice, permitting conditional EC-specific depletion of the transcription factor Serum Response Factor (SRF), suffer from loss of BBB integrity and intracerebral hemorrhaging. Cerebral microbleeds and larger hemorrhages developed upon postnatal and adult depletion of either SRF or its cofactors Myocardin Related Transcription Factor (MRTF-A/-B), revealing essential requirements of ongoing SRF/MRTF activity for maintenance of cerebral small vessel integrity. In vivo magnetic resonance imaging allowed detection, localization, and time-resolved quantification of BBB permeability and hemorrhage formation in Srf(iECKO) brains. At the molecular level, direct and indirect SRF/MRTF target genes, encoding structural components of tight junctions (Claudins and ZO proteins), adherens junctions (VE-cadherin, alpha-Actinin), and the basement membrane (Collagen IV), were down-regulated upon SRF depletion. These results identify SRF and its MRTF cofactors as major transcriptional regulators of EC junctional stability, guaranteeing physiological functions of the cerebral microvasculature. We hypothesize that impairments in SRF/MRTF activity contribute to human SVD pathology.","Animals;Animals, Newborn;Astrocytes/metabolism/pathology;Basement Membrane/metabolism/pathology;Blood-Brain Barrier/metabolism;Brain/blood supply/metabolism/pathology/physiopathology;Cadherins/metabolism;Cerebral Hemorrhage/ complications/metabolism/pathology/physiopathology;Collagen Type IV/metabolism;Down-Regulation;Endothelial Cells/ metabolism;Evans Blue/metabolism;Exploratory Behavior;Extravasation of Diagnostic and Therapeutic Materials;Gene Deletion;Magnetic Resonance Imaging;Mice, Knockout;Microvessels/metabolism/pathology;Motor Activity;Permeability;Serum Response Factor/genetics/ metabolism;Stroke/ etiology/ metabolism/pathology/physiopathology;Tight Junctions/metabolism;Time Factors;Trans-Activators/ metabolism;Transcription Factors/ metabolism","Weinl, C.;Castaneda Vega, S.;Riehle, H.;Stritt, C.;Calaminus, C.;Wolburg, H.;Mauel, S.;Breithaupt, A.;Gruber, A. D.;Wasylyk, B.;Olson, E. N.;Adams, R. H.;Pichler, B. J.;Nordheim, A.",2015,Aug 11,10.1073/pnas.1509047112,0,
396,"Brain MRI, apoliprotein E genotype, and plasma homocysteine in American Indian Alzheimer disease patients and Indian controls","We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).","Aged;Aged, 80 and over;Alzheimer Disease/*blood/ethnology/*genetics;Apolipoprotein E4/genetics;Apolipoproteins E/*genetics;Brain/metabolism/*pathology/physiopathology;DNA Mutational Analysis;Female;Genetic Predisposition to Disease/*genetics;Genetic Testing;Genotype;Homocysteine/*blood;Humans;Hyperhomocysteinemia/blood/complications/ethnology;Indians, North American;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Polymorphism, Genetic/genetics","Weiner, M. F.;de la Plata, C. M.;Fields, B. A.;Womack, K. B.;Rosenberg, R. N.;Gong, Y. H.;Qu, B. X.;Diaz-Arrastia, R.;Hynan, L. S.",2009,Feb,,0,
397,Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT),"BACKGROUND: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. STUDY DESIGN: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). PREDICTORS: Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). OUTCOMES: Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging. RESULTS: Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8+/-20.9mL/min/1.73m(2) and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. LIMITATIONS: Cross-sectional only, no patients with diabetes were included. CONCLUSIONS: In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.","Aged;Blood Pressure Determination/methods;Cardiovascular Diseases/epidemiology;Cognition/ physiology;Cognition Disorders/diagnosis/physiopathology;Cross-Sectional Studies;Female;Glomerular Filtration Rate;Humans;Hypertension/diagnosis/psychology;Intelligence Tests;Kidney Function Tests/methods;Magnetic Resonance Imaging/methods;Male;Renal Insufficiency, Chronic/diagnosis/psychology;Risk Factors;Statistics as Topic;White Matter/diagnostic imaging;Kidney disease;albuminuria;brain;brain imaging;cardiovascular disease (CVD);cerebrovascular disease;cognition;dementia;estimated glomerular filtration rate (eGFR);executive function;global cognitive function;kidney function;memory;neurocognitive test battery;urinary albumin-creatinine ratio (UACR);white matter volume","Weiner, D. E.;Gaussoin, S. A.;Nord, J.;Auchus, A. P.;Chelune, G. J.;Chonchol, M.;Coker, L.;Haley, W. E.;Killeen, A. A.;Kimmel, P. L.;Lerner, A. J.;Oparil, S.;Saklayen, M. G.;Slinin, Y. M.;Wright, C. B.;Williamson, J. D.;Kurella Tamura, M.;Group, Sprint Study Research",2017,Sep,,0,
398,"Albuminuria, Cognitive Functioning, and White Matter Hyperintensities in Homebound Elders","Background: Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain. Study Design: Cross sectional. Setting & Participants: Boston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging. Predictor: Urine albumin-creatinine ratio (ACR). Outcome: Performance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models. Results: In 335 participants, mean age was 73.4 ± 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (β = -0.05; P = 0.005 in univariate and β = -0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (β = 0.11; P = 0.007; β = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria. Limitations: Single measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history. Conclusions: Albuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden. © 2009 National Kidney Foundation, Inc.",,"Weiner, D. E.;Bartolomei, K.;Scott, T.;Price, L. L.;Griffith, J. L.;Rosenberg, I.;Levey, A. S.;Folstein, M. F.;Sarnak, M. J.",2009,March,,0,
399,A novel Notch3 deletion mutation in a Chinese patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare autosomal dominant hereditary cerebrovascular disease characterised by migraine attacks, recurrent subcortical transient ischemic attacks or strokes, cognitive decline, and dementia. It is caused by mutations in the Notch3 gene on chromosome 19p13.1, which is the only gene currently known to be closely associated with CADASIL. We describe a novel 100 base pair base fragment deletion mutation (ENST 00000263388, c.512-611del) in the Notch3 gene from a Chinese patient with CADASIL. The present patient has the characteristic clinical and family history for CADASIL, which suggests that C.512del611 may be a cause of CADASIL as well as most of the previously reported Notch3 mutations. © 2012 Elsevier Ltd. All rights reserved.",adult;article;base pairing;CADASIL;case report;Chinese;chromosome 19p;controlled study;DNA sequence;exon;family history;female;gene;gene deletion;genetic screening;human;intron;medical history;neuroimaging;NOTCH3 gene;nuclear magnetic resonance imaging;polymerase chain reaction;priority journal,"Weiming, F.;Yuliang, W.;Youjie, L.;Xinsheng, L.;Shuyang, X.;Zhaoxia, L.",2013,,,0,
400,Structural connectivity of the default mode network and cognition in Alzheimer's disease,"Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer's disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0. T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60degree) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network. 2014 Elsevier Ireland Ltd.",adult;aged;Alzheimer disease;article;brain atrophy;cell structure;cognition;comparative study;computer program;connectome;controlled study;default mode network;diffusion tensor imaging;female;fractional anisotropy;human;major clinical study;male;mild cognitive impairment;priority journal;randomized controlled trial;white matter,"Weiler, M.;Campos, B. M.;Nogueira, M. H.;Pereira Damasceno, B.;Cendes, F.;Balthazar, M. L. F.",2014,,10.1016/j.pscychresns.2014.04.008,0,
401,"Following the Spreading of Brain Structural Changes in Alzheimer's Disease: A Longitudinal, Multimodal MRI Study","BACKGROUND: Longitudinal MRI studies in Alzheimer's disease (AD) are one of the most reliable way to track brain changes along the course of the disease. OBJECTIVE: To investigate the evolution of grey matter (GM) atrophy and white matter (WM) damage in AD patients, and to assess the relationships of MRI changes with baseline clinical and cognitive variables and their evolution over time. METHODS: Clinical, neuropsychological, and MRI assessments (T1-weighted and diffusion tensor [DT]-MRI) were obtained from 14 patients with AD at baseline and after a 16 +/- 3 month period. Lumbar puncture was obtained at study entry. At baseline, AD patients were compared to 37 controls. GM atrophy progression was assessed with tensor-based morphometry and GM volumes of interest, and WM damage progression using tract-based spatial statistics and tractography. RESULTS: At baseline, patients showed cortical atrophy in the medial temporal and parietal regions and a widespread pattern of WM damage involving the corpus callosum, cingulum, and temporo-occipital, parietal, and frontal WM tracts. During follow up, AD patients showed total GM atrophy, while total WM volume did not change. GM tissue loss was found in frontal, temporal, and parietal regions. In addition, AD patients showed a progression of WM microstructural damage to the corpus callosum, cingulum, fronto-parietal and temporo-occipital connections bilaterally. Patients with higher baseline cerebrospinal fluid total tau showed greater WM integrity loss at follow up. GM and WM changes over time did not correlate with each other nor with cognitive evolution. CONCLUSION: In AD, GM atrophy and WM tract damage are likely to progress, at least partially, independently. This study suggests that a multimodal imaging approach, which includes both T1-weighted and DT MR imaging, may provide additional markers to monitor disease progression.",,"Weiler, M.;Agosta, F.;Canu, E.;Copetti, M.;Magnani, G.;Marcone, A.;Pagani, E.;Balthazar, M. L.;Comi, G.;Falini, A.;Filippi, M.",2015,,10.3233/jad-150196,0,
402,"Assessment of paramedian thalamic infarcts: MR imaging, clinical features and prognosis","Considering the highly variable vascular supply of the thalamic nuclei, MRI and clinical syndromes can be heterogeneous in ischemic diseases. We attempt to determine MRI pattern and to analyse neurological features and prognosis of paramedian infarcts. In a prospective case series within 5 years from 1999 to 2003, MRI, MRA and clinical symptoms of 38 consecutive patients were analysed. The inferomedial (posterior thalamoperforating artery) territory was affected in 89%, and lesions in the anterolateral (tuberothalamic artery) territory occurred in 42%. However, definite attribution to anterolateral or inferomedial territories was not possible in 13%. Neurological manifestations were somnolence (87%), hemisyndromes (79%), cognitive deficits (58%), oculomotor nerve palsies (53%) and vertical gaze palsies (39%). The most common aetiologies were cardiac embolism (42%), intraarterial embolism (16%), small vessel disease (13%) and large artery arteriosclerosis (13%). Pathological MRA findings were encountered in 55%, and in 18%, lesions were only visible on diffusion-weighted imaging. Correlation of MRI pattern and neurological symptoms points out anterolateral thalamic lesions as the cause of amnestic deficits. Intracranial MRA allows a non-invasive prediction of basilar tip occlusion. Our results underline the necessity of additional diffusion-weighted imaging in detecting small thalamic and midbrain lesions. © Springer-Verlag 2004.",,"Weidauer, S.;Nichtweiß, M.;Zanella, F. E.;Lanfermann, H.",2004,September,,0,
403,"The relationship between cerebral white matter hyperintensities and lower urinary tract function in a population based, geriatric cohort","INTRODUCTION: White matter hyperintensities (WHM) in cerebral MRI-scan have been suspected to be involved in the pathogenesis for geriatric LUTS. Aim of this study was to investigate this association in a geriatric cohort. MATERIALS AND METHODS: The VITA-study is a prospective, population-based study initiated 2000/2001. All inhabitants of a well-defined area in Vienna aged 75 years were recruited and underwent detailed regular visits including cerebral MRI-scans. Subcortical and periventricular WMHs were classified according to the Fazekas-classification. In 2010, all subjects alive were contacted to complete the Bristol LUTS questionnaire. RESULTS: Two hundred seventeen participants (75 men, 142 women), all 85 years old, entered this analysis. Urgency, frequency, and nocturia was present in 39 (50.7%), 53 (52%), and 55 (73.3%) men and 79 (55.6%), 81 (78.2%), and 68 (47.9%) women, respectively. OAB symptoms were seen in 55% of women and 50% of men. At baseline, WMH were present in 68.2% and this percentage increased to 85.7% at the most recent follow-up. Several symptoms were more prevalent in participants without WMH as compared to those with WMH, (urgency: 71% vs. 53%, P=0.06, nocturia: 77% vs. 53%, P=0.01: OAB-symptoms: 71% vs. 51%, P=0.05. Only frequency was more prevalent in participants with WMH (77% vs. 68%, P=0.27). In general, sub-categorization into periventricular and subcortical WMH confirmed these data. Furthermore the amount of WMH-burden did not correlate to LUT dysfunction. CONCLUSION: This study failed to demonstrate a clear association between several aspects of LUTS and WMH in a rather healthy, population-based 85-year-old cohort.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Brain/*pathology;Cohort Studies;Female;Humans;Longitudinal Studies;Lower Urinary Tract Symptoms/etiology/*pathology;Magnetic Resonance Imaging;Male;Predictive Value of Tests;Prospective Studies;Sex Characteristics;Luts;Vita;Wmh;geriatric;over active bladder;white matter hyperintensities","Wehrberger, C.;Jungwirth, S.;Fischer, P.;Tragl, K. H.;Krampla, W.;Marlies, W.;Madersbacher, S.",2014,Apr,10.1002/nau.22419,0,
404,APOE status and its association to learning and memory performance in middle aged and older Norwegians seeking assessment for memory deficits,"BACKGROUND: We examined the hypothesis that deficits in learning, memory, and other cognitive functions are associated with the epsilon4 allele of the Apolipoprotein E (APOE) gene in a non-demented sample with memory complaints recruited from a population with a high prevalence of this allele. METHODS: The study group comprised 70 consecutively referred patients aged 50-75 seeking assessment due to memory complaints. They were screened for dementia, for neurological and psychiatric disease, and for cerebral infarction using Magnet Resonance Imaging (MRI). Participants were classified as non-demented based on clinical evaluation and results on cognitive tests. RESULTS: APOE epsilon4 carriers (56% of the sample) showed poorer performance than non-carriers on the Mini Mental State Examination, a number of measures of verbal memory function from the California Verbal Learning Test, and visual recall. In 46% of the participants, psychometric criteria for amnestic Mild Cognitive Impairment (aMCI) were satisfied. CONCLUSION: Findings may be partly explained by a significant number of participants being in a preclinical phase of Alzheimer's disease. The observed deficits in learning performance and the lack of significant age modulation of the genetic association suggest a more general genetic effect. The findings are consistent with known neurobiological function of APOE epsilon4, including both increased risk of neurodegenerative disease and reduced synaptic integrity in older age.",,"Wehling, E.;Lundervold, A. J.;Standnes, B.;Gjerstad, L.;Reinvang, I.",2007,,10.1186/1744-9081-3-57,0,
405,Structural and functional cortical disconnection in Alzheimer's disease: A combined study using diffusion tensor imaging and transcranial magnetic stimulation,"We investigated the functional consequences of compromised white matter integrity in Alzheimer's disease by combining Diffusion Tensor Imaging (DTI) and Transcranial Magnetic Stimulation (TMS) in 19 patients with AD (Alzheimer's disease) and 19 healthy controls. We used a region of interest approach and correlated the ipsilateral silent period (iSP) and the resting motor threshold (RMT) from TMS with fractional anisotropy (FA) and mean diffusivity (MD) values of the corpus callosum and corticospinal tract. AD patients showed significant reductions of FA in intracortical projecting fibre tracts compared to controls and widespread increases in MD. TMS data showed increased latency of iSP in AD patients and a decreased RMT, indicating decreased motor cortical inhibition. Although both TMS and DTI metrics were prominently altered in AD patients, impaired white matter integrity was not associated with increased iSP latency or reduced RMT, as correlation of TMS parameters with FA and MD values in the a priori defined regions showed no significant effects. Therefore, we argue that beside the direct degeneration of the underlying fibre tracts, other pathophysiological mechanisms may account for the observation of decreased transcallosal inhibition and increased motor excitability in AD. © 2012 Elsevier Ireland Ltd.",,"Wegrzyn, M.;Teipel, S. J.;Oltmann, I.;Bauer, A.;Thome, J.;Großmann, A.;Hauenstein, K.;Höppner, J.",2013,30,,0,
406,Enriched white matter connectivity networks for accurate identification of MCI patients,"Mild cognitive impairment (MCI), often a prodromal phase of Alzheimer's disease (AD), is frequently considered to be a good target for early diagnosis and therapeutic interventions of AD. Recent emergence of reliable network characterization techniques has made it possible to understand neurological disorders at a whole-brain connectivity level. Accordingly, we propose an effective network-based multivariate classification algorithm, using a collection of measures derived from white matter (WM) connectivity networks, to accurately identify MCI patients from normal controls. An enriched description of WM connections, utilizing six physiological parameters, i.e., fiber count, fractional anisotropy (FA), mean diffusivity (MD), and principal diffusivities(lambda(1), lambda(2), and lambda(3)), results in six connectivity networks for each subject to account for the connection topology and the biophysical properties of the connections. Upon parcellating the brain into 90 regions-of-interest (ROIs), these properties can be quantified for each pair of regions with common traversing fibers. For building an MCI classifier, clustering coefficient of each ROI in relation to the remaining ROIs is extracted as feature for classification. These features are then ranked according to their Pearson correlation with respect to the clinical labels, and are further sieved to select the most discriminant subset of features using an SVM-based feature selection algorithm. Finally, support vector machines (SVMs) are trained using the selected subset of features. Classification accuracy was evaluated via leave-one-out cross-validation to ensure generalization of performance. The classification accuracy given by our enriched description of WM connections is 88.9%, which is an increase of at least 14.8% from that using simple WM connectivity description with any single physiological parameter. A cross-validation estimation of the generalization performance shows an area of 0.929 under the receiver operating characteristic (ROC) curve, indicating excellent diagnostic power. It was also found, based on the selected features, that portions of the prefrontal cortex, orbitofrontal cortex, parietal lobe and insula regions provided the most discriminant features for classification, in line with results reported in previous studies. Our MCI classification framework, especially the enriched description of WM connections, allows accurate early detection of brain abnormalities, which is of paramount importance for treatment management of potential AD patients.","Aged;Algorithms;Brain/*pathology;Cell Count;Cognition Disorders/*diagnosis/pathology;Data Interpretation, Statistical;Female;Humans;Image Processing, Computer-Assisted/methods;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers/physiology;Nerve Net/*pathology;Neural Pathways/pathology;Neuropsychological Tests;Nonlinear Dynamics;ROC Curve;Reproducibility of Results","Wee, C. Y.;Yap, P. T.;Li, W.;Denny, K.;Browndyke, J. N.;Potter, G. G.;Welsh-Bohmer, K. A.;Wang, L.;Shen, D.",2011,Feb 1,10.1016/j.neuroimage.2010.10.026,0,
407,Longitudinal diffusion tensor imaging in Huntington's Disease,"Serial diffusion tensor imaging scans were collected at baseline and 1 year follow-up to investigate the neurodegenerative profile of white matter (WM) in seven individuals with the Huntington's Disease (HD) gene mutation and seven control subjects matched on age and gender. In the HD subjects, but not controls, a significant reduction of fractional anisotropy (FA), a measure of WM integrity, between baseline and followup was evident throughout the brain. In addition, a DTI scalar associated with the stability of axons, axial diffusivity, showed significant longitudinal decreases from year 1 to year 2 in HD subjects, declines that overlapped to greater degree with FA discrepancies than longitudinal increases in radial diffusivity, a DTI variable sensitive to demylinization. These preliminary results provide the first longitudinal DTI evidence of WM degeneration in HD and support the notion that FA abnormalities in HD may be a result of axonal injury or withdrawal. These results suggest that longitudinal FA changes may serve as a neuropathological biomarker in HD.",Adult;Brain/ pathology;Brain Mapping;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Huntington Disease/ pathology;Longitudinal Studies;Male;Middle Aged;Young Adult,"Weaver, K. E.;Richards, T. L.;Liang, O.;Laurino, M. Y.;Samii, A.;Aylward, E. H.",2009,Apr,10.1016/j.expneurol.2008.12.026,0,
408,Diagnostic imaging of patients in a memory clinic: Comparison of MR imaging and 64-detector row CT,"Purpose: To investigate the assessment of global cortical atrophy (GCA), medial temporal lobe atrophy (MTA), and white matter changes (WMCs) in patients screened at a memory clinic with a 64-detector row computed tomography (CT) brain protocol, in comparison with the reference standard, magnetic resonance (MR) imaging. Materials and Methods: The study protocol was approved by the local institutional review board. Written informed consent was obtained from all participants. Thirty patients (21 men, nine women; median age, 62 years) who presented to a memory clinic underwent 64-detector row CT and multisequence MR imaging of the brain on the same day. Three readers blinded to the clinical diagnosis assessed the resultant images. Images were presented in random order and scored for GCA, MTA, and WMC with published visual rating scales. Intermodality agreement between CT and MR imaging (intrareader agreement across both modalities), expressed by weighted κ analysis, and interobserver agreement within each modality between readers (Kendall W test) were assessed. Results: Overall, excellent intraobserver agreement between CT and MR imaging was observed for GCA (mean κ, 0.83) and MTA (mean κ, 0.88 and 0.86 on the left and right sides of the brain, respectively). There was substantial overall agreement concerning WMC (mean κ, 0.79). For all three tested scales, interobserver variability was low and comparable for CT and MR imaging. Conclusion: Use of 64-detector row brain CT yields reliable information that is comparable with that obtained with MR imaging. Thus, multidetector row CT is a suitable diagnostic imaging tool in a memory clinic setting. © RSNA, 2009.",,"Wattjes, M. P.;Henneman, W. J. P.;Van Der Flier, W. M.;De Vries, O.;Träber, F.;Geurts, J. J. G.;Scheltens, P.;Vrenken, H.;Barkhof, F.",2009,October,,0,
409,Characterizing dementia with Lewy bodies by means of diffusion tensor imaging,"OBJECTIVE: To investigate patterns of in vivo white matter tract change using diffusion tensor imaging (DTI), we conducted a cross-sectional study of dementia with Lewy bodies (DLB) in comparison with Alzheimer disease (AD) and normal aging. METHODS: The study included 106 subjects (35 with DLB, 36 with AD, and 35 elderly controls) who underwent clinical and neuropsychological assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate patterns of reduced fractional anisotropy (FA) and increased mean diffusivity (MD) across the entire white matter tract skeleton and also investigated correlations with clinical features. RESULTS: Areas of reduced FA in subjects with DLB vs controls were found primarily in parieto-occipital white matter tracts; in AD, the changes were much more diffuse. DLB was also associated with reduced FA in the pons and left thalamus, in comparison with AD. The pattern of MD increase was diffuse in AD and DLB. We found an association between DTI parameters and impaired episodic memory, letter fluency, and severity of motor parkinsonism in DLB. CONCLUSIONS: Despite a similar level of dementia severity, patterns of DTI changes in AD and DLB differed significantly. The selective involvement of the visual association areas and subcortical structures and the significant clinical correlations highlight the potential importance of white matter tract change in the pathogenesis of DLB. DTI may be a useful technique to investigate early and possible preclinical changes in DLB and warrants further investigation.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Anisotropy;Cerebral Cortex/pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted;Lewy Body Disease/ pathology;Male;Memory, Episodic;Neuropsychological Tests;Parkinson Disease/complications/physiopathology;Pons/pathology;Psychomotor Performance/physiology;Pyramidal Tracts/pathology;Thalamus/pathology","Watson, R.;Blamire, A. M.;Colloby, S. J.;Wood, J. S.;Barber, R.;He, J.;O'Brien, J. T.",2012,Aug 28,10.1212/WNL.0b013e318266fc51,0,
410,Use of calcium channel blockers is associated with better cognitive performance in older hypertensive patients with subjective memory complaints,"Background Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention. Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints. Patients and methods Three hundred and seventy-eight elderly hypertensive patients more than 60 years (mean age 70.4W6.3 years) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospectively recruited and underwent a combination of neuropsychological tests, brain magnetic resonance imaging with semiquantification of white matter hyperintensities, carotid echotracking, brachial endothelial function, and ambulatory blood pressure assessments. Results None of the three composite scores (memory score, verbal fluency, and visual memory capacity) was found associated with blood pressure levels. On the other hand, age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers (CCBs) (users: R0.14W0.09 versus nonusers: S0.12W0.06; PU0.016). Multivariate analyses also revealed that CCB use was significantly associated with a better memory score, independently of age, male sex, white matter hyperintensities, and carotid wall cross-sectional area, all of which were associated with worse memory scores. Conclusion In elderly hypertensive treated patients with subjective memory complaints, CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations, suggesting a specific neuroprotective effect of this pharmacological class. Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline © 2010 Wolters Kluwer Health.",,"Watfa, G.;Rossignol, P.;Kearney-Schwartz, A.;Fay, R.;Bracard, S.;Felblinger, J.;Boivin, J. M.;Lacolley, P.;Zannad, F.;Benetos, A.",2010,December,,0,
411,Association study of gene polymorphisms involved in vascular alterations in elderly hypertensives with subjective memory complaints,"BACKGROUND: We have recently shown that vascular abnormalities are associated with cognitive impairment as well as with white matter hyperintensities (WMH) in elderly hypertensive patients presenting with subjective memory complaints (SMC), a population at high risk of developing dementia. The aim of the present study was to identify genetic variants associated with the degree of cognitive impairment and the severity of WMH in the same study population, focusing on genes involved in vascular alterations. METHODS: 50 gene polymorphisms known to be associated with vascular alterations (blood pressure regulation, lipid and homocysteine metabolism, thrombosis and inflammation) were genotyped using a multilocus genotyping assay in 369 elderly treated hypertensive patients >60 years of age and presenting with SMC but no dementia. The patients underwent a combination of neuropsychological tests and brain magnetic resonance imaging with semiquantification of WMH. RESULTS: None of the tested polymorphisms were found to be associated with age- and gender-adjusted memory score, visual capacity, body-mass-index-adjusted verbal fluency score or the age-adjusted WMH Fazekas score. CONCLUSION: Our results suggest that the associations between arterial factors and cognitive decline or WMH are not genetically driven by the genes we investigated, at least at this early stage of cognitive decline.","Aged;Aged, 80 and over;Apolipoproteins E/genetics;Blood Pressure/genetics/physiology;Blood Vessels/ pathology;Cognition Disorders/genetics/psychology;Cross-Sectional Studies;Data Interpretation, Statistical;Female;Genetic Association Studies;Genetic Variation;Genotype;Homocysteine/metabolism;Humans;Hypertension/ genetics/ pathology/psychology;Inflammation/genetics;Lipid Metabolism/genetics;Magnetic Resonance Imaging;Male;Memory Disorders/ genetics/ pathology/psychology;Middle Aged;Multigene Family/genetics;Polymorphism, Genetic/ genetics;Thrombosis/genetics","Watfa, G.;Marteau, J. B.;Rossignol, P.;Kearney-Schwartz, A.;Fay, R.;Bracard, S.;Felblinger, J.;Boivin, J. M.;Lacolley, P.;Visvikis-Siest, S.;Benetos, A.;Zannad, F.",2010,,10.1159/000321120,0,
412,Paramedian thalamic and midbrain infarction: the 'mesencephalothalamic syndrome',"Paramedian infarction in the region of the thalamus and upper midbrain may produce a wide range of neuro-ophthalmological, behavioural and motor abnormalities. The paramedian arteries arise from the first part of the posterior cerebral artery, also known as the basilar communicating artery. The particular arterial topography and its anatomical variation may result in unusual combinations of clinical signs, and infarction may be bilateral in some cases. Diagnosis is often aided by CT scanning and magnetic resonance imaging. Both atherosclerotic occlusion and embolism are thought to be responsible for these particular syndromes. We describe 3 cases that illustrate some of the various clinical features and underlying anatomical vascular arrangements which may be seen in this condition. Thalamic dementia was present in one case with evidence of bilateral thalamic infarction. A complex ophthalmoplegia and hemiparesis were seen in another case, and the third case had a combination of thalamic dementia and ophthalmoplegia.",,"Waterston, J. A.;Stark, R. J.;Gilligan, B. S.",1987,1987,,0,
413,Steroid-responsive limbic encephalitis,"A 71-year-old man presented with gradually progressing cognitive decline following acute febrile exanthematous disorder. The MRI showed an abnormality in the bilateral limbic systems. An elevation of cerebrospinal fluid (CSF) protein with lymphocyte pleocytosis was noted. Immunoblot of the CSF revealed the presence of anti-white matter antibodies that mainly recognized astrocytes. Intravenous steroid followed by oral steroid reduced the symptoms to a remarkable degree. The patient has now been successfully sustained with steroid for more than two years. We considered that this case is classified as non-paraneoplastic limbic encephalitis, and acquired autoimmunity played a major role in the pathogenesis of this case.",aciclovir;cell antibody;methylprednisolone;myelin basic protein;nonsteroid antiinflammatory agent;prednisolone;steroid;valproic acid;virus antibody;aged;article;astrocyte;autoimmunity;case report;cognitive defect;drug response;electroencephalography;human;immunoblotting;immunopathogenesis;limbic system;lymphocyte;male;molecular recognition;neurologic examination;nuclear magnetic resonance imaging;paraneoplastic neuropathy;pleocytosis;protein cerebrospinal fluid level;skin manifestation;symptomatology;treatment outcome;white matter,"Watanabe, Y.;Shimizu, Y.;Ooi, S.;Tanaka, K.;Inuzuka, T.;Nakashima, K.",2003,,,0,
414,Absolute quantification in proton magnetic resonance spectroscopy is superior to relative ratio to discriminate Alzheimer's disease from Binswanger's disease,"BACKGROUND/AIMS: Although many proton magnetic resonance spectroscopy studies have assessed the relative ratios of brain metabolites from patients with dementia, absolute quantification is rare. The aim of this study is to compare the diagnostic accuracy of these 2 methods in proton magnetic resonance spectroscopy in discriminating Alzheimer's disease (AD) and Binswanger's disease (BD) from healthy controls (HC). METHODS: The subjects were 30 AD patients, 13 BD patients and 26 HC subjects. Single-voxel proton MR spectra at short echo times were acquired from 8 volumes of interest. RESULTS: At 80% specificity, the absolute N-acetylaspartate concentration in the hippocampus was the most sensitive measure to discriminate AD from HC, and the absolute N-acetylaspartate concentration in the anterior periventricular and deep white matter to differentiate BD from HC and AD. No relative ratio using creatine as a reference had a sensitivity over 80% at 80% specificity. The cause of disparities between the 2 methods was attributed to fluctuations in the creatine concentration. CONCLUSION: Our study revealed that absolute quantification is superior to relative ratio to differentiate AD and BD from HC.","0 (Protons);30KYC7MIAI (Aspartic Acid);4L6452S749 (Inositol);997-55-7 (N-acetylaspartate);MU72812GK0 (Creatine);N91BDP6H0X (Choline);Aged;Alzheimer Disease/ diagnosis/metabolism;Aspartic Acid/analogs & derivatives/metabolism;Choline/metabolism;Creatine/metabolism;Dementia, Vascular/ diagnosis/metabolism;Diagnosis, Differential;Female;Hippocampus/metabolism/pathology;Humans;Inositol/metabolism;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy/ methods/ standards;Male;Middle Aged;Occipital Lobe/metabolism/pathology;Prospective Studies;Protons;Reproducibility of Results;Sensitivity and Specificity","Watanabe, T.;Shiino, A.;Akiguchi, I.",2008,,,0,415
415,Absolute quantification in proton magnetic resonance spectroscopy is superior to relative ratio to discriminate Alzheimer's disease from Binswanger's disease,"BACKGROUND/AIMS: Although many proton magnetic resonance spectroscopy studies have assessed the relative ratios of brain metabolites from patients with dementia, absolute quantification is rare. The aim of this study is to compare the diagnostic accuracy of these 2 methods in proton magnetic resonance spectroscopy in discriminating Alzheimer's disease (AD) and Binswanger's disease (BD) from healthy controls (HC). METHODS: The subjects were 30 AD patients, 13 BD patients and 26 HC subjects. Single-voxel proton MR spectra at short echo times were acquired from 8 volumes of interest. RESULTS: At 80% specificity, the absolute N-acetylaspartate concentration in the hippocampus was the most sensitive measure to discriminate AD from HC, and the absolute N-acetylaspartate concentration in the anterior periventricular and deep white matter to differentiate BD from HC and AD. No relative ratio using creatine as a reference had a sensitivity over 80% at 80% specificity. The cause of disparities between the 2 methods was attributed to fluctuations in the creatine concentration. CONCLUSION: Our study revealed that absolute quantification is superior to relative ratio to differentiate AD and BD from HC.","Alzheimer Disease [diagnosis] [metabolism];Aspartic Acid [analogs & derivatives] [metabolism];Choline [metabolism];Creatine [metabolism];Dementia, Vascular [diagnosis] [metabolism];Diagnosis, Differential;Hippocampus [metabolism] [pathology];Inositol [metabolism];Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy [methods] [standards];Occipital Lobe [metabolism] [pathology];Prospective Studies;Protons;Reproducibility of Results;Sensitivity and Specificity;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Watanabe, T.;Shiino, A.;Akiguchi, I.",2008,,10.1159/000144044,0,
416,Prognosis of the lower extremity function with aging in patients with postapoplectic hemiplegia and factors interfering with rehabilitation - Especially in the octogenarians,"In order to assess the prognosis of the lower extremity function and factors interfering with rehabilitation in patients with postapoplectic hemiplegia in relation to aging, 98 patients ranging in age between 43 and 87 years with fixed lesions measuring less than 15 mm in actual size in the unilateral posterior limb of the internal capsule in the brain CT scan were analyzed and the following results were obtained. I. Prognosis of the lower extremity function: 1) Incidence of walking by oneself decreased and gait disturbance increased with aging, suggesting a major influence of aging. 2) The qualitative content of walking by oneself (a rate occupying walking with the assistance of a cane and outdoor walking by oneself) decreased with aging, with a tendency towards sudden decrease in the octogenarians. The object of rehabilitation in the majority of the octogenarians appears to be the return to home life and independence of the activities of daily living. 3) As to the site and size of the lesions, the prognosis in patients with the lesion in the posterior one-half of the posterior limb of the internal capsule was unfavorable regardless of the size of the lesion. 4) No difference was noted according to the disease type of cerebral hemorrhage and infarction and side of hemiplegia. II. Factors interfering with rehabilitation: 1) Incidence of the reduction of muscle strength on the uninvolved side, decrease of volition, urinary incontinence and dementia showed a positive correlation with age. The first two increased in the octogenarians and the latter in the seventies. 2) In the octogenarians, the reduction of muscle strength on the uninvolved side, decrease of volition and urinary incontinence were correlated with the prognosis of the lower extremity function. Dementia only showed a tendency of correlation. The former 3 factors were intimately correlated with gait disturbance in the prognosis of the lower extremity function. Dementia, on the other hand, showed a negative correlation with walking by oneself. 3) The muscle strength on the uninvolved side in the octogenarians rapidly and readily decreased on acute bedridden state, so that rehabilitation measures should be taken as quickly as possible. The factors interfering with rehabilitation including aging are closely related to one another, and it appears quite rare that one of these factors alone determines the prognosis of the lower extremity function.",aged;central nervous system;etiology;hemiplegia;human;leg function;major clinical study;musculoskeletal system;nervous system;peripheral vascular system;rehabilitation;cerebrovascular accident;therapy,"Watanabe, T.;Kimura, H.;Saito, H.",1985,,,0,
417,Proton magnetic resonance spectroscopy and white matter hyperintensities on magnetic resonance imaging in patients with Alzheimer's disease,,"Aged;Alzheimer Disease/ metabolism/pathology;Brain/ metabolism/ pathology;Brain Mapping/ methods;Dementia, Vascular/metabolism/pathology;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy/methods;Male;Reference Values","Watanabe, T.;Akiguchi, I.;Yagi, H.;Onishi, K.;Kawasaki, T.;Shiino, A.;Inubushi, T.",2002,Nov,,0,
418,Brain SPECT with neuro-Behcet disease,"A patient with neuro-Behcet disease is described. SPECT using Tc-99m HMPAO was performed to evaluate brain perfusion. The brain SPECT revealed decreased perfusion in the right frontal, parietal, temporal, and occipital lobes. MRI showed high Intensity lesions in the white matter in the right periventricular centrum semi-ovale and frontal region on T2 weighted images. Gray matter abnormalities were evident on brain SPECT, but not on MRI. Brain SPECT using Tc-99m HMPAO may provide useful clinical information on regional cerebral cortical abnormalities associated with neuro-Behcet disease.",,"Watanabe, N.;Seto, H.;Sato, S.;Simizu, M.;Wu, Y. W.;Kageyama, M.;Nomura, K.;Kakishita, M.",1995,1995,,0,
419,Preferentially affected sites of cerebral arteriosclerosis in vascular dementia of Binswanger type - A study of MRI and MR angiography,"MRI and MR angiography (MRA) were analyzed to evaluate the preferential sites of cerebral arteriosclerosis in 129 normal controls and 27 patients with vascular dementia of Binswanger type (BVD; mean age 75.0 years). Small vessel disease, indicated as advanced high intensity areas on T2-weighted MRI, increased with advancing age, while large vessel sclerosis detected with MRA did not increase after the age of 80 years. Large vessel sclerosis was not always accompanied with advanced high intensity areas. Large vessel sclerosis was found in 12 (44.4%) of 27 patients with BVD, and was as common as that of the controls of the eighth decade. Large vessel sclerosis was frequently seen in the cases suffering from BVD below 70 years of age or with hypertension. In conclusion, patients with BVD develop cerebral arteriosclerosis more preferentially in the small vessels rather than the large vessels especially in aged cases, of which incidence is similar to that of the normal controls over 80 years of age.",adult;aged;angiography;article;brain atherosclerosis;controlled study;female;human;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance,"Watanabe, M.;Takahashi, A.;Yoneyama, S.",1994,,,0,420
420,[Preferentially affected sites of cerebral arteriosclerosis in vascular dementia of Binswanger type--a study of MRI and MR angiography],"MRI and MR angiography (MRA) were analyzed to evaluate the preferential sites of cerebral arteriosclerosis in 129 normal controls and 27 patients with vascular dementia of Binswanger type (BVD; mean age 75.0 years). Small vessel disease, indicated as advanced high intensity areas on T2-weighted MRI, increased with advancing age, while large vessel sclerosis detected with MRA did not increase after the age of 80 years. Large vessel sclerosis was not always accompanied with advanced high intensity areas. Large vessel sclerosis was found in 12 (44.4%) of 27 patients with BVD, and was as common as that of the controls of the eighth decade. Large vessel sclerosis was frequently seen in the cases suffering from BVD below 70 years of age or with hypertension. In conclusion, patients with BVD develop cerebral arteriosclerosis more preferentially in the small vessels rather than the large vessels especially in aged cases, of which incidence is similar to that of the normal controls over 80 years of age.","Age Factors;Aged;Aged, 80 and over;Aging/pathology;Dementia, Vascular/*complications;Female;Humans;Intracranial Arteriosclerosis/*diagnosis/pathology;Magnetic Resonance Angiography;*Magnetic Resonance Imaging;Male;Middle Aged","Watanabe, M.;Takahashi, A.;Yoneyama, S.",1994,Nov,,0,
421,Remission of lymphomatosis cerebri induced by corticosteroid and high-doses intravenous methotrexate,"Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma characterized by subacute progressive dementia and unsteady gait MRI study of LC typically reveals diffuse leukoencephalopathy without contrast enhancement. The clinical presentation and MRI features of LC can resemble infectious, inflammatory, toxic or vascular leukoencephalopathy. Hence diagnosis of LC is easily mistaken for other, more common diseases. In this report, we present a case of a 55-year-old man presenting with subacute progressive dementia and ataxic gait. Brain MRI showed diffuse hyperintense lesions in the cerebral white matter of both hemispheres, left amygdala, brainstem and cerebellar peduncles on FLAIR image. No contrast-enhanced lesion was observed. Cerebrospinal fluid analysis showed elevated levels of soluble interleukin-2 receptor and β2-microglobulin. Based on MRI findings and (123)I-IMP SPECT, stereotactic biopsy targeting white matter of the left medial temporal lobe was performed (day 0). On the day after the brain biopsy, corticosteroid therapy was initiated and improved the patient's cognitive function and gait disturbance. Pathological diagnosis of large B-cell lymphoma was obtained on day 9. High-dose intravenous methotrexate chemotherapy was started on day 14 and led to complete remission by day 52. This case highlighted the importance of brain biopsy for diagnosis of LC. This report raises a possibility that timely and proper treatment leads to a favorable outcome of LC that has been regarded as an intractable disease with poor prognosis.",,"Watanabe, M.;Satoi, H.;Takahashi, Y.;Nishida, N.;Toda, H.;Matsumoto, S.",2012,July,,0,
422,An unusual case of elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with multiple cerebrovascular risk factors,"Here we report a female patient with elderly-onset cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). At age 71, she developed gait disturbance, followed by memory disturbance 1 year later. She had been treated for hypertension and diabetes mellitus for 19 years. There apparently was low penetrance of disease. Magnetic resonance imaging (MRI) findings showed typical features of CADASIL, and the R607C mutation was detected in exon 11 in NOTCH3. This case strongly indicates that CADASIL should be considered when typical findings are observed on MRI even in cases of elderly onset with multiple cerebrovascular risk factors. © 2012 by National Stroke Association.",,"Watanabe, M.;Adachi, Y.;Jackson, M.;Yamamoto-Watanabe, Y.;Wakasaya, Y.;Shirahama, I.;Takamura, A.;Matsubara, E.;Kawarabayashi, T.;Shoji, M.",2012,February,,0,
423,Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure,"Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 +/- 2.4 years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4 Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 +/- 7.3 years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain.","Adult;Aging;Alleles;Alzheimer Disease/ genetics;Anisotropy;Cholesterol/ blood;Cholesterol Ester Transfer Proteins/ genetics;Diffusion Magnetic Resonance Imaging;Female;Follow-Up Studies;Forecasting;Humans;Male;Myelin Sheath/metabolism;Polymorphism, Single Nucleotide;Risk;White Matter/ pathology;Young Adult","Warstadt, N. M.;Dennis, E. L.;Jahanshad, N.;Kohannim, O.;Nir, T. M.;McMahon, K. L.;de Zubicaray, G. I.;Montgomery, G. W.;Henders, A. K.;Martin, N. G.;Whitfield, J. B.;Jack, C. R., Jr.;Bernstein, M. A.;Weiner, M. W.;Toga, A. W.;Wright, M. J.;Thompson, P. M.",2014,Nov,10.1016/j.neurobiolaging.2014.05.024,0,
424,Cognitive impact of lacunar infarcts and white matter hyperintensity volume,"Background: Subcortical lacunar infarcts and white matter hyperintensities (WMH) are common neuroradiological findings, but few studies associate between these insults and cognition in a community-dwelling population. Methods: The Dallas Heart Study is a populationbased initiative whose assessments included demographic and clinical findings including brain MRI and the Montreal Cognitive Assessment (MoCA). The presence and number of lacunes in subjects aged over 55 years were assessed by study physicians. The WMH volume was measured by an automated method. The association between the presence and number of lacunar infarcts and of WMH volume with the total MoCA score and subdomains was assessed using linear regression with adjustment for age, gender and self-reported ethnicity. Results: In 609 subjects with valid data, both the presence and the increasing number of lacunes were associated with lower MoCA scores, even after adjusting for demographic variables. The presence of lacunes was also associated with lower scores in the memory, executive and attention subdomains. The WMH volume was not significantly associated with the MoCA score. Conclusion: The presence and increasing number of lacunes in midlife is associated with a lower performance in multiple domains of a cognitive screening measure after adjusting for demographic factors.",adult;aged;article;attention;cognition;depth perception;educational status;executive function;female;human;lacunar stroke;language;major clinical study;male;memory;Montreal cognitive assessment;neuroimaging;nuclear magnetic resonance imaging;orientation;priority journal;race difference;radiological parameters;white matter;white matter hyperintensity volume,"Warren, M. W.;Weiner, M. F.;Rossetti, H. C.;McColl, R.;Peshock, R.;King, K. S.",2015,,,0,
425,Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study,"Introduction Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage. Methods We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency. Results In 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P <.0001), with WMH severity (P =.033), age (P =.03), and hypertension (P <.0001). BBB leakage in WMH predicted declining cognition at 1 year. Discussion BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.",adult;aged;article;blood brain barrier;brain interstitial fluid;cerebrovascular accident;cognition;cohort analysis;cortical ischemic stroke;dementia;human;hypertension;lacunar stroke;major clinical study;neuroimaging;priority journal;prospective study;recurrent disease;tissue specificity;very elderly;white matter,"Wardlaw, J. M.;Makin, S. J.;Valdés Hernández, M. C.;Armitage, P. A.;Heye, A. K.;Chappell, F. M.;Muñoz-Maniega, S.;Sakka, E.;Shuler, K.;Dennis, M. S.;Thrippleton, M. J.",2017,,10.1016/j.jalz.2016.09.006,0,426
426,Blood-brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: Evidence from a cohort study,"Introduction: Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage. Methods: We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency. Results: In 201 patients, median age 67 (range 34-97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year. Discussion: BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.",adult;aged;blood brain barrier;blood vessel;brain cortex;cerebrovascular accident;cognition;cohort analysis;dementia;human;human tissue;hypertension;imaging;interstitial fluid;major clinical study;prevention;spatial analysis;treatment failure;white matter,"Wardlaw, J. M.;Makin, S. J.;Valdés Hernández, M. C.;Armitage, P. A.;Heye, A. K.;Chappell, F. M.;Muñoz-Maniega, S.;Sakka, E.;Shuler, K.;Dennis, M. S.;Thrippleton, M. J.",2016,,10.1016/j.jalz.2016.09.006,0,
427,"Vascular risk factors, large-artery atheroma, and brain white matter hyperintensities","Objective: To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 prospective cohorts. Methods: We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH. Results: In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years [SD ±0.7 years], 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years [SD ±11.6 years], 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used. Conclusions: The small effect of VRFs and LAD on WMH suggests that WMH have a large ""nonvascular,"" nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed. © 2014 American Academy of Neurology.",aged;article;atheroma;cardiovascular risk;cerebrovascular accident;female;human;hypertension;leg;major clinical study;male;nuclear magnetic resonance imaging;priority journal;prospective study;scoring system;stroke patient;white matter,"Wardlaw, J. M.;Allerhand, M.;Doubal, F. N.;Hernandez, M. V.;Morris, Z.;Gow, A. J.;Bastin, M.;Starr, J. M.;Dennis, M. S.;Deary, I. J.",2014,,,0,
428,Blood-brain barrier and cerebral small vessel disease,"Increasing evidence from neuro and retinal imaging, neuropathology, epidemiology and experimental models suggests that the primary underlying initiating cause of cerebral small vessel disease is the derangement of the blood-brain barrier. This may start some years before the first symptoms, leads to the small vessel structural changes (vessel wall thickening, disorganisation and eventual breakdown) and perivascular changes (oedema, enlarged perivascular spaces, tissue damage interpreted as ""infarcts"") and is fundamentally different to traditional ""ischaemic"" mechanisms, although small vessel occlusion due to thrombus formation on damaged vessel walls may be a late secondary phenomenon. Space limits a detailed discussion of the epidemiology and experimental evidence, so this brief review will focus on neuroimaging evidence and summarise the appearances, risk factors and associations of different components of cerebral small vessel disease as identified on imaging, discuss potential causes and, in particular, the evidence that disordered blood-brain barrier precipitates or worsens progression of cerebral small vessel disease. This mechanism may also play a role in other common disorders of ageing such as Alzheimer's disease. © 2010 Elsevier B.V. All rights reserved.",,"Wardlaw, J. M.",2010,15,,0,
429,Recent developments in imaging of stroke,"• Radiological assessment plays a crucial role in directing optimal primary treatment and secondary prevention of stroke. • CT or brain MRI is required to identify the approximately 4% of patients who have a non-vascular cause of stroke, e.g. tumour. • Judicious and timely use of CT is the most cost effective way of distinguishing ischaemic from haemorrhagic stroke. • CT cannot reliably distinguish infarct from haemorrhage more than 8 days after stroke. • In the UK, there are still far too many patients with a stroke or transient ischaemic attack not receiving a CT brain scan at all, or receiving one far too late to distinguish infarct from haemorrhage. • A gradient echo MR sequence is required to identify haemorrhage reliably with MRI. • MR diffusion/perfusion imaging and CT perfusion imaging are promising but experimental techniques. © 2002 The British Institute of Radiology.",,"Wardlaw, J. M.",2002,2002,,0,
430,Microbleeds in cerebral small vessel disease - Authors' reply,,blood brain barrier;brain hemorrhage;cerebrovascular disease;diffusion tensor imaging;human;immunohistochemistry;letter;nuclear magnetic resonance imaging;priority journal;vascular amyloidosis;water content,"Wardlaw, J.;Smith, C.;Dichgans, M.",2013,,,0,
431,"The Study of Neurocognitive Outcomes, Radiological and Retinal Effects of Aspirin in Sleep Apnoea- rationale and methodology of the SNORE-ASA study","PURPOSE: Sleep disordered breathing (SDB) is highly prevalent in older adults. Increasing evidence links SDB to the risk of dementia, mediated via a number of pathways, some of which may be attenuated by low-dose aspirin. This study will evaluate, in a healthy older cohort, the prospective relationship between SDB and cognitive function, changes in retinal and cerebral microvasculature, and determine whether low-dose aspirin ameliorates the effects of SDB on these outcomes over 3years. DESIGN: SNORE-ASA is a sub-study of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, multi-centre, placebo-controlled trial evaluating the effect of daily 100mg aspirin on disability-free and dementia-free survival in the healthy older adult aged 70 and over. At baseline, 1400 ASPREE participants successfully underwent a home sleep study with a home sleep study screening device for SDB; and 296 underwent both 1.5 Tesla brain magnetic resonance imaging (MRI) and retinal vascular imaging (RVI). Cognitive testing, brain MRI and RVI is being repeated after 3years. PRIMARY OUTCOME MEASURES: Change in the modified mini-mental state examination score. Secondary outcome measures are changes in other cognitive tests, and changes in abnormal parameters on RVI and volume of white matter hyper-intensities on brain MRI. CONCLUSION: Identifying preventive therapies for delaying the onset of dementia is of paramount importance. The results of this study will help clarify the impact of the SDB on risk of cognitive decline and cerebral small vessel disease, and whether low-dose aspirin can ameliorate cognitive decline in the setting of SDB. SNORE-ASA TRIAL REGISTRATION: ACTRN12612000891820: The Principal ASPREE study is registered with the International Standardized Randomized Controlled Trials Register, ASPirin in Reducing Events in the Elderly, Number: ISRCTN83772183 and clinicaltrials.gov Number NCT01038583.",Brain magnetic resonance imaging;Cognitive decline;Dementia;Low-dose aspirin;Retinal vascular imaging;Sleep disordered breathing,"Ward, S. A.;Storey, E.;Woods, R. L.;Hamilton, G. S.;Kawasaki, R.;Janke, A. L.;Naughton, M. T.;O'Donoghue, F.;Wolfe, R.;Wong, T. Y.;Reid, C. M.;Abhayaratna, W. P.;Stocks, N.;Trevaks, R.;Fitzgerald, S.;Hodgson, L. A. B.;Robman, L.;Workman, B.;McNeil, J. J.;Group, Aspree Study",2018,Jan,,0,
432,"ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly","Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.",0 (Fibrinolytic Agents);R16CO5Y76E (Aspirin);Aged;Aspirin/ administration & dosage/adverse effects;Brain/diagnostic imaging/drug effects;Cerebral Hemorrhage/chemically induced/diagnostic imaging/ epidemiology;Cognition/ drug effects;Double-Blind Method;Fibrinolytic Agents/ administration & dosage/adverse effects;Humans;International Cooperation;Magnetic Resonance Imaging;Patient Selection;Risk Assessment;Sample Size;Stroke/diagnostic imaging/epidemiology/ prevention & control;White Matter/diagnostic imaging/ drug effects;Cerebral microbleeds;aspirin;cognitive decline;dementia;healthy aging;neuroimaging;small vessel disease,"Ward, S. A.;Raniga, P.;Ferris, N. J.;Woods, R. L.;Storey, E.;Bailey, M. J.;Brodtmann, A.;Yates, P. A.;Donnan, G. A.;Trevaks, R. E.;Wolfe, R.;Egan, G. F.;McNeil, J. J.;on behalf of the, Aspree investigator group",2017,Jan,,0,
433,"ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly","RATIONALE: Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. AIMS: ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. SAMPLE SIZE: Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. METHODS AND DESIGN: A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. STUDY OUTCOMES: The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. DISCUSSION: ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613001313729.",Cerebral microbleeds;aspirin;cognitive decline;dementia;healthy aging;neuroimaging;small vessel disease,"Ward, S. A.;Raniga, P.;Ferris, N. J.;Woods, R. L.;Storey, E.;Bailey, M. J.;Brodtmann, A.;Yates, P. A.;Donnan, G. A.;Trevaks, R. E.;Wolfe, R.;Egan, G. F.;McNeil, J. J.",2016,Sep 15,10.1177/1747493016669848,0,
434,The effect of body mass index on global brain volume in middle-aged adults: A cross sectional study,"Background: Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy. The purpose of this study was to determine whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women. Methods: T1-weighted 3D volumetric magnetic resonance imaging was used to assess global brain volume for 114 individuals 40 to 66 years of age (average=54.2 years; standard deviation=6.6 years; 43 men and 71 women). Total cerebrospinal fluid and brain volumes were obtained with an automated tissue segmentation algorithm. A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition. Results: Age and BMI were each associated with decreased brain volume. BMI did not predict cognition in this sample; however elevated diastolic blood pressure was associated with poorer episodic learning performance. Conclusions: These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may potentially be at greater risk for future cognitive decline. © 2005 Ward et al., licensee BioMed Central Ltd.",,"Ward, M. A.;Carlsson, C. M.;Trivedi, M. A.;Sager, M. A.;Johnson, S. C.",2005,,,0,
435,Low HDL Cholesterol is Associated with Lower Gray Matter Volume in Cognitively Healthy Adults,"Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect. T1-weighted magnetic resonance imaging was used to examine regional brain gray matter (GM) and white matter (WM) in 183 individuals (58.4 +/- 8.0 years) using voxel-based morphometry. A non-parametric multiple linear regression model was used to assess the effect of high-density lipoprotein (HDL) and non-HDL cholesterol, APOE, and FHAD on regional GM and WM volume. A post hoc analysis was used to assess whether any significant correlations found within the volumetric analysis had an effect on cognition. HDL was positively correlated with GM volume in the bilateral temporal poles, middle temporal gyri, temporo-occipital gyri, and left superior temporal gyrus and parahippocampal region. This effect was independent of APOE and FHAD. A significant association between HDL and the Brief Visuospatial Memory Test was found. Additionally, GM volume within the right middle temporal gyrus, the region most affected by HDL, was significantly associated with the Controlled Oral Word Association Test and the Center for Epidemiological Studies Depression Scale. These findings suggest that adults with decreased levels of HDL cholesterol may be experiencing cognitive changes and GM reductions in regions associated with neurodegenerative disease and therefore, may be at greater risk for future cognitive decline.",,"Ward, M. A.;Bendlin, B. B.;McLaren, D. G.;Hess, T. M.;Gallagher, C. L.;Kastman, E. K.;Rowley, H. A.;Asthana, S.;Carlsson, C. M.;Sager, M. A.;Johnson, S. C.",2010,,10.3389/fnagi.2010.00029,0,
436,Increased protein-conjugated acrolein and amyloid-β40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer's disease,"The objective of this study was to determine whether plasma levels of acrolein, a compound that causes cell damage, and amyloid-β (Aβ) are useful biochemical markers for Alzheimer's disease (AD). The study included 221 elderly subjects divided into 101 non-demented [33 healthy control and 68 non-demented subjects with white matter hyperintensity (nd-WMH)], 50 mild cognitive impairment (MCI), and 70 AD. Increases in both protein-conjugated acrolein (PC-Acro) and Aβ40/42 ratio were observed in MCI and AD patients compared with values in control subjects. When the combined measurements of PC-Acro and Aβ40/42 ratio were evaluated using the median value of the relative risk value for dementia, they were in the order AD (0.98) ≥ MCI (0.97) > nd-WMH (0.83) > control (0.35). The results indicate that measurements of PC-Acro and Aβ40/42 ratio not only detect MCI and AD patients but also nd-WMH subjects. Furthermore, both PC-Acro and Aβ40/42 ratio in plasma for 120 MCI and AD patients were significantly higher than those for 101 control and nd-WMH subjects, indicating that both values become useful biochemical markers for MCI and AD subjects. © 2012 - IOS Press and the authors. All rights reserved.",acrolein;amyloid beta protein[1-40];amyloid beta protein[1-42];C reactive protein;interleukin 6;adult;Alzheimer disease;article;cell damage;conjugation;controlled study;dementia;female;human;major clinical study;male;mild cognitive impairment;priority journal;protein blood level;risk factor;white matter,"Waragai, M.;Yoshida, M.;Mizoi, M.;Saiki, R.;Kashiwagi, K.;Takagi, K.;Arai, H.;Tashiro, J.;Hashimoto, M.;Iwai, N.;Uemura, K.;Igarashi, K.",2012,,,0,
437,Increased protein-conjugated acrolein and amyloid-beta40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer's disease,"The objective of this study was to determine whether plasma levels of acrolein, a compound that causes cell damage, and amyloid-beta (Abeta) are useful biochemical markers for Alzheimer's disease (AD). The study included 221 elderly subjects divided into 101 non-demented [33 healthy control and 68 non-demented subjects with white matter hyperintensity (nd-WMH)], 50 mild cognitive impairment (MCI), and 70 AD. Increases in both protein-conjugated acrolein (PC-Acro) and Abeta40/42 ratio were observed in MCI and AD patients compared with values in control subjects. When the combined measurements of PC-Acro and Abeta40/42 ratio were evaluated using the median value of the relative risk value for dementia, they were in the order AD (0.98) >/= MCI (0.97) > nd-WMH (0.83) > control (0.35). The results indicate that measurements of PC-Acro and Abeta40/42 ratio not only detect MCI and AD patients but also nd-WMH subjects. Furthermore, both PC-Acro and Abeta40/42 ratio in plasma for 120 MCI and AD patients were significantly higher than those for 101 control and nd-WMH subjects, indicating that both values become useful biochemical markers for MCI and AD subjects.","Acrolein/*blood;Adult;Aged;Aged, 80 and over;Alzheimer Disease/*blood/pathology;Amyloid beta-Peptides/*blood;Atrophy;Biomarkers/blood;Brain/pathology;C-Reactive Protein/metabolism;Female;Humans;Image Processing, Computer-Assisted;Interleukin-6/blood;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/*blood/pathology;Neuropsychological Tests;Peptide Fragments/*blood","Waragai, M.;Yoshida, M.;Mizoi, M.;Saiki, R.;Kashiwagi, K.;Takagi, K.;Arai, H.;Tashiro, J.;Hashimoto, M.;Iwai, N.;Uemura, K.;Igarashi, K.",2012,,10.3233/jad-2012-120253,0,
438,MRI and SPECT studies of dural arteriovenous fistulas presenting as pure progressive dementia with leukoencephalopathy: A cause of treatable dementia,"We report two patients with dural arteriovenous fistulas (DAVFs) who presented with pure progressive dementia. Both patients showed only slowly progressive dementia, without headache, papilledema and other neurologic signs associated with diffuse white matter changes in MRI. MR cerebral angiography showed sigmoid sinus DAVFs that were mainly supplied by the occipital artery, together with retrograde filling of the superior sagittal and straight sinus and dilated cortical veins. SPECT studies showed extensive blood flow reduction in the occipital and parieto-occipital areas and right temporal lobe in one patient. Selective embolization for treatment of the DAVF improved cognitive function associated with the abnormal white matter MRI signal. MRI and SPECT showed that severity of dementia correlated with diffuse white matter changes and regional cerebral blood flow. Our cases suggest that gradually impaired cerebral circulation due to venous hypertensive encephalopathy could be involved in slowly progressive dementia with leukoencephalopathy resulting from a DAVF. DAVFs may be particularly important for differential diagnosis in elderly patients with pure progressive dementia. Thus, early diagnosis of DAVFs and treatment by endovascular surgery is important as treatable or reversible dementia. © 2006 EFNS.",adult;article;artificial embolism;brain angiography;brain arteriovenous malformation;brain blood flow;case report;clinical feature;cognition;correlation analysis;dementia;disease severity;human;leukoencephalopathy;male;neurologic examination;nuclear magnetic resonance imaging;priority journal;single photon emission computer tomography;white matter,"Waragai, M.;Takeuchi, H.;Fukushima, T.;Haisa, T.;Yonemitsu, T.",2006,,,0,
439,Clinical and radiological features of the late-onset methylmalonic aciduria: A review of three cases,"Objective: To study the clinical and radiological features of the patients with late-onset methylmalonic aciduria (MMA). Methods: Two men and one woman with MMA were screened and confirmed by urinary organic acid analysis with gas chromatograph/mass spectrometer (GC/MS) at their 26, 18 and 34 years old, respectively. Their clinical features, laboratory findings, radiological manifestations, treatment and outcome were reviewed. Results: The clinical features of 3 patients were varied with neurological abnormalities. Case 1 had periodic enuresis for 16 months, progressive dementia and movement disorder for 3 months. Physical examination showed an apparent cognitive decline with psychiatric symptoms. Dysarthria, bilateral weakness and pyramidal signs, rigidity and mild tremor of limbs were observed. Case 2 had a progressive memory deterioration, learning difficulty, walking unstably and decreased vision when he was 13 years old, and a general seizure at an age of 16 years. Diffused abnormalities of EEG and mild renal defects were found in the above two patients. General white matter hyperintensity and cerebral atrophy on T2-weighted MR images were evident. Additionally, these two patients had hyperhomocystinemia and carnitine deficiency. Case 3 had complained about walking unstably and fatigue over 2 months. Reduced facial movements, deep sensation loss and muscle weakness in lower extremities, marked rigidity and diminished tendon reflexes were detected. Megaloblastic anemia and cobalamin deficiency were found. MRI performed revealed bilateral symmetric areas having high density involving the globi pallidi, posterior limbs of internal capsule and the cerebral peduncles. Remarkable elevations of urinary methylmalonic and methylcitric acid were confirmed in all 3 patients. After vitamin B(12) supplementation, significant improvement was observed. Conclusion: Three cases with vitamin B(12) responsive type of late-onset MMA were reported. Two patients were combined with hyperhomocystinemia and the other had only isolated MMA. There might remain prominent differences among MMA subgroups in clinical presentations and neuroradiologic findings. Vitamin B(12) might be very effective to improve the prognosis of the patients. MMA should be considered as a differential diagnosis for the etiological investigation of adult cerebral metabolic or degenerative diseases.",,"Wang, Z. X.;Zhang, W.;Yang, Y. L.;Yuan, Y.",2004,Aug,,0,
440,NOTCH3 mutations and clinical features in 33 mainland Chinese families with CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in NOTCH3. Although CADASIL cases have been identified worldwide, the data from mainland China are still limited. OBJECTIVE: To identify NOTCH3 mutations and analyse the clinical and MRI findings in a large series of CADASIL patients from mainland China. METHODS: Direct sequencing of NOTCH3 and/or skin or sural nerve biopsies were performed on 48 unrelated suspected CADASIL cases of Chinese descent. The clinical manifestations and MRI features were retrospectively collected and analysed in the 33 index patients with confirmed diagnosis and their available affected family members. RESULTS: 20 different NOTCH3 mutations were identified in 33 families, including seven novel mutations. The highest mutation frequency was in exons 4 (55%) and 3 (30%). Granular osmiophilic material in smooth muscle cells was found in 30 cases who were biopsied. Clinical presentation included TIA/stroke in 82%, cognitive decline in 60%, and migraine with aura in only 5% of 57 symptomatic cases. MRI detected multiple lacunar infarcts and leucoaraiosis in all symptomatic cases, brainstem lesions in 64% of symptomatic cases and white-matter lesions in the temporal pole in 46% of affected members. CONCLUSIONS: The mutational spectrum and primary clinical features of patients with CADASIL from mainland China are similar to those in Caucasians. However, migraine with aura and abnormal white matter in the temporal pole are less common than among Caucasians, while brainstem involvement is more common than among Caucasians.","Brain/pathology;CADASIL/*genetics/pathology;China;Genetic Association Studies;Humans;Magnetic Resonance Imaging;Mutation/genetics;Mutation, Missense/genetics;Polymorphism, Single Nucleotide/genetics;Receptors, Notch/*genetics;Sequence Deletion/genetics","Wang, Z.;Yuan, Y.;Zhang, W.;Lv, H.;Hong, D.;Chen, B.;Liu, Y.;Luan, X.;Xie, S.;Wu, S.",2011,May,10.1136/jnnp.2010.209247,0,
441,Cerebral microbleeds and cognitive function in ischemic stroke or transient ischemic attack patients,"Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.",,"Wang, Z.;Wong, A.;Liu, W.;Yang, J.;Chu, W. C. W.;Au, L.;Lau, A.;Chan, A.;Xiong, Y.;Soo, Y.;Leung, T.;Wong, L. K. S.;Mok, V. C. T.",2015,2,,0,
442,Pulse Pressure and Cognitive Decline in Stroke Patients With White Matter Changes,"The authors hypothesized that both high and low pulse pressure (PP) may predict cognitive decline in stroke/transient ischemic attack (TIA) patients with white matter changes (WMCs). The authors prospectively followed up 406 ischemic stroke/TIA patients with confluent WMCs over 18 months. PP was measured at 3 to 6 months after stroke/TIA and categorized into four groups by quartile. Cognition was assessed 3 to 6 months and 15 to 18 months after stroke/TIA using the Clinical Dementia Rating and Mini-Mental State Examination (MMSE). Logistic regression showed that patients in the first quartile of PP had a 5.9-fold higher risk for developing cognitive decline than patients in the third quartile (odds ratio, 5.9; 95% confidence interval, 1.7-20.6), while patients in the fourth quartile had a 3.5-fold higher risk for cognitive decline than those in the third quartile (odds ratio, 3.5; 95% confidence interval, 1.0-12.4). This U-shaped relationship was also evident between PP and cognitive decline in MMSE, underlining the role of arterial stiffness and hypoperfusion in cognitive decline related to small vessel disease.","Aged;Blood Pressure/*physiology;Cognition Disorders/*diagnosis/etiology/pathology;Dementia/etiology/*pathology;Female;Follow-Up Studies;Humans;Ischemic Attack, Transient/*diagnosis/pathology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Predictive Value of Tests;Prospective Studies;Risk Factors;Stroke/*pathology/psychology;White Matter/*pathology/radiography","Wang, Z.;Wong, A.;Liu, W.;Yang, J.;Chu, W. C.;Au, L.;Lau, A.;Xiong, Y.;Mok, V. C.",2015,Sep,10.1111/jch.12583,0,
443,Interhemispheric Functional and Structural Disconnection in Alzheimer's Disease: A Combined Resting-State fMRI and DTI Study,"Neuroimaging studies have demonstrated that patients with Alzheimer's disease presented disconnection syndrome. However, little is known about the alterations of interhemispheric functional interactions and underlying structural connectivity in the AD patients. In this study, we combined resting-state functional MRI and diffusion tensor imaging (DTI) to investigate interhemispheric functional and structural connectivity in 16 AD, 16 mild cognitive impairment (MCI), as well as 16 cognitive normal healthy subjects (CN). The pattern of the resting state interhemispheric functional connectivity was measured with a voxel-mirrored homotopic connectivity (VMHC) method. Decreased VMHC was observed in AD and MCI subjects in anterior brain regions including the prefrontal cortices and subcortical regions with a pattern of AD<MCI<CN. Increased VMHC was observed in MCI subjects in posterior brain regions with patterns of AD/CN < MCI (sensorimotor cortex) and AD < CN/MCI (occipital gyrus). DTI analysis showed the most significant difference among the three cohorts was the fractional anisotropy in the genu of corpus callosum, which was positively associated with the VMHC of prefrontal and subcortical regions. Across all the three cohorts, the diffusion parameters in the genu of corpus callosum and VMHC in the above brain regions had significant correlation with the cognitive performance. These results demonstrate that there are specific patterns of interhemispheric functional connectivity changes in the AD and MCI, which can be significantly correlated with the integrity changes in the midline white matter structures. These results suggest that VMHC can be used as a biomarker for the degeneration of the interhemispheric connectivity in AD.",Aged;Alzheimer Disease/ diagnosis/pathology/physiopathology;Brain/pathology/physiopathology;Diffusion Tensor Imaging/ methods;Female;Humans;Magnetic Resonance Spectroscopy/ methods;Male,"Wang, Z.;Wang, J.;Zhang, H.;McHugh, R.;Sun, X.;Li, K.;Yang, Q. X.",2015,,10.1371/journal.pone.0126310,0,
444,Risk Factors and Cognitive Relevance of Cortical Cerebral Microinfarcts in Patients With Ischemic Stroke or Transient Ischemic Attack,"BACKGROUND AND PURPOSE—: It was recently demonstrated that cerebral microinfarcts (CMIs) can be detected in vivo using 3.0 tesla (T) magnetic resonance imaging. We investigated the prevalence, risk factors, and the longitudinal cognitive consequence of cortical CMIs on 3.0T magnetic resonance imaging, in patients with ischemic stroke or transient ischemic attack. METHODS—: A total of 231 patients undergoing 3.0T magnetic resonance imaging were included. Montreal Cognitive Assessment was used to evaluate global cognitive functions and cognitive domains (memory, language, and attention visuospatial and executive functions). Cognitive changes were represented by the difference in Montreal Cognitive Assessment score between baseline and 28-month after stroke/transient ischemic attack. The cross-sectional and longitudinal associations between cortical CMIs and cognitive functions were explored using ANCOVA and regression models. RESULTS—: Cortical CMIs were observed in 34 patients (14.7%), including 13 patients with acute (hyperintense on diffusion-weighted imaging) and 21 with chronic CMIs (isointense on diffusion-weighted imaging). Atrial fibrillation was a risk factor for all cortical CMIs (odds ratio, 4.8; 95% confidence interval, 1.5–14.9; P=0.007). Confluent white matter hyperintensities was associated with chronic CMIs (odds ratio, 2.8; 95% confidence interval, 1.0–7.8; P=0.047). The presence of cortical CMIs at baseline was associated with worse visuospatial functions at baseline and decline over 28-month follow-up (β=0.5; 95% confidence interval, 0.1–1.0; P=0.008, adjusting for brain atrophy, white matter hyperintensities, lacunes, and microbleeds). CONCLUSIONS—: Cortical CMIs are a common finding in patients with stroke/transient ischemic attack. Associations between CMI with atrial fibrillation and white matter hyperintensities suggest that these lesions have a heterogeneous cause, involving microembolism and cerebral small vessel disease. CMI seemed to preferentially impact visuospatial functions as assessed by a cognitive screening test.",analysis of covariance;atrial fibrillation;attention;brain atrophy;brain hemorrhage;confidence interval;diffusion weighted imaging;executive function;follow up;human;language;major clinical study;memory;microembolism;Montreal cognitive assessment;odds ratio;prevalence;risk factor;screening test;statistical model;transient ischemic attack;white matter,"Wang, Z.;van Veluw, S. J.;Wong, A.;Liu, W.;Shi, L.;Yang, J.;Xiong, Y.;Lau, A.;Biessels, G. J.;Mok, V. C. T.",2016,,,0,
445,Correlation of early neurological deterioration and white matter hyperintensities in patients with acute lacunar infarction,"Objective: To investigate the predictors of early neurological deterioration (END) as well as the correlation between white matter hyperintensities (WMH) and END in patients with acute ischemic stroke. Methods: Consecutive patients diagnosed as acute lacunar infarction and admitted to Jinling Hospital between 4.5 and 24.0 hours after symptom onset were prospectively recruited in the study. END was defined as an increase of National Institutes of Health Stroke Scale (NIHSS) score ≥2 points in the first 72 hours after admission. Besides, all patients received magnetic resonance imaging within 24 hours after admission. The WMH were graded according to the Fazekas rating scale. Results: A total of 223 patients were finally enrolled. Of them, 70 (31.4%) patients suffered END in the initial 72 hours after admission. Multivariable analysis indicated that systolic blood pressure (OR=1.02, 95% CI 1.00-1.04, P=0.049), baseline NIHSS score (OR=1.32, 95% CI 1.15-1.52, P<0.01) and fasting plasma glucose on admission (OR=1.14,95% CI 1.01-1.29, P=0.034) were independent predictors for END. However, for periventricular WMH, compared to Fazekas grade 0, no statistically significant correlation existed between END and WMH grade 1, grade 2 and grade 3. For WMH in centrum semiovale, similarly, END did not correlate with WMH grade 1, grade 2 and grade 3.Likewise, in the post-hoc subgroup analysis of patients with different age, sex and different territory, END did not significantly correlate with WMH neither in periventricular nor in centrum semiovale. Conclusions: Systolic blood pressure, baseline NIHSS score and the fasting plasma glucose on admission were independent predictors for END in patients with acute lacunar infarction. However, WMH located neither in periventricular spaces nor in centrum semiovale was related to END.",,"Wang, Z.;Li, Y.;Xiao, L.;Duan, Z.;Ma, N.;Sun, W.;Liu, D.;Liu, X.",2014,1,,0,
446,Cortical Thickness and Microstructural White Matter Changes Detect Amnestic Mild Cognitive Impairment,"Both the apolipoprotein E (APOE) varepsilon4 allele and amnestic mild cognitive impairment (aMCI) are considered to be risk factors for Alzheimer's disease (AD). The primary aim of this study was to determine whether the aMCI-related abnormality in gray matter (GM) cortical thickness and white matter (WM) tracts integrity would be modified by the APOE genotype. A total of 146 older adults, including 64 aMCI patients (28 varepsilon4 carriers and 36 non-carriers) and 82 healthy controls (39 varepsilon4 carriers and 43 non-carriers), underwent a standardized clinical interview, neuropsychological battery assessment, and multi-modal brain magnetic resonance imaging scans. Compared with control subjects, the patients with aMCI showed significantly reduced cortical thickness bilaterally in the parahippocampal gyrus and disrupted WM integrity in the limbic tracts (e.g., increased mean diffusivity in the right parahippocampal cingulum and bilateral uncinate fasciculus). However, no significant main effects of the APOE genotype and diagnosis-by-genotype interaction on GM thickness and WM integrity were observed. Further, diffusivity measures of the limbic WM tracts were significantly correlated with the parahippocampal atrophy in aMCI. Importantly, the parahippocampal thickness and diffusivity measures of the limbic WM tracts were significantly correlated with the cognitive performance (i.e., episodic memory Z score) in patients with aMCI. These results demonstrate that WM microstructural disruptions in the limbic tracts are present at the early stage of AD in an APOE-independent manner; and this degeneration may occur progressively, in parallel with parahippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.",Alzheimer's disease;amnestic mild cognitive impairment;apolipoprotein E;cortical thickness;white matter integrity,"Wang, Z.;Dai, Z.;Shu, H.;Liu, D.;Guo, Q.;He, Y.;Zhang, Z.",2017,,,0,
447,Progress in clinicopathologic research of lymphomatosis cerebri,"Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma. It presents usually as rapidly progressive dementia and is accompanied by extensive white matter changes without formation of a cohesive mass in magnetic resonance imaging (MRI). The main pathological feature is diffuse infiltration in the white matter by individual neoplastic cells without formation of a cohesive tumor mass. The neurobehavioral deficits manifested by the patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome. Early pathological examination is important for specific treatment and interventions. Although more attention has been paid on lymphomatosis cerebri in clinical course, the knowledge about this disease is still on the base of case reports and lacks of systematic analysis both at home and abroad. We reviewed the case reports abroad and collected clinical and pathological data of 17 individuals who were diagnosed lymphomatosis cerebri through biopsy and (or) autopsy in the hope of deep and overall recognition of this disease.",,"Wang, Y. J.;Piao, Y. S.;Lu, D. H.",2012,October,,0,
448,Associations between EEG Beta Power Abnormality and Diagnosis in Cognitive Impairment Post Cerebral Infarcts,"Cerebral infarct is a common disease of older adults, which could increase the risk for cognitive impairment and dementia. Electroencephalogram (EEG) characteristics were analyzed to investigate the applied value in the assessment of cognitive impairment of the cerebral infarct patients. One hundred ten subjects with cerebral infarcts (including 65 cases of cognitive impairment patients (CI-CI) and 45 cases of cognitive normality patients (CI-NC)) and 110 normal health persons (NC) were recruited between July 2009 and March 2011 at the Department of Neurology. All of the patients were analyzed by EEG within 1 day they were hospitalized. The EEG analysis results were compared with the Montreal Cognitive Assessment (MoCA) scale (assessed within 2 weeks) with the methods of correlation analysis, clustering analysis, and concordance analysis. The results indicated that CI-CI patients had significantly lower EEG beta power (0.832 ± 0.203 mcV2) relative to the CI-NC group (1.493 ± 0.271 mcV2, P < 0.01) or NC group (1.565 ± 0.345 mcV2, P < 0.01). Significant negative correlation between the beta power and infarct size (as well as infarct number) was discovered (r = -0.88881 and -0.66498, respectively, both P < 0.001). There was a good concordance between K-means clustering algorithm calculating the beta power and MoCA scoring (Kappa = 0.851, P < 0.001). The preliminary findings suggest that the recognition techniques of EEG hold considerable promise for the assessment of cognitive impairment post cerebral infarcts within 2 weeks and which related to the size of infarcts and number of infarcts. © 2012 Springer Science+Business Media New York.",aged;algorithm;article;beta rhythm;brain infarction;brain infarction size;brain ischemia;clinical assessment;cluster analysis;cognitive defect;computer assisted tomography;controlled study;correlation analysis;EEG abnormality;electroencephalogram;female;human;major clinical study;male;nuclear magnetic resonance imaging;pattern recognition,"Wang, Y.;Zhang, X.;Huang, J.;Zhu, M.;Guan, Q.;Liu, C.",2013,,,0,
449,Risk factors of cerebral microbleeds in strictly deep or lobar brain regions differed,"Background T2∗-weighted gradient echo magnetic resonance imaging is sensitive in detecting cerebral microbleeds (MBs), but there are few reports on the risk factors of MBs in different brain regions. Therefore, we aimed to investigate whether the risk factors associated with the presence of MBs in strictly deep or lobar brain regions were different. Methods This study consisted of 696 consecutive acute ischemic stroke patients from 6 hospitals in the Chinese IntraCranial AtheroSclerosis Study. We evaluated the number and location of MBs, severity of lacune and leukoaraiosis (LA), and etiologic subtype of ischemic stroke. Multivariable logistic regression was used to analyze risk factors of MBs in different brain regions. Results Among 696 acute ischemic stroke patients, 162 patients (23.3%) had MBs. Of them, 62 patients had strictly deep brain MBs, 49 patients had strictly lobar MBs. There was a significant correlation between the number of MBs, the number of lacune, and the severity of LA (P <.0001). In multivariable logistic regression analysis, both strictly deep and strictly lobar brain, MBs were significantly associated with history of cerebral hemorrhage (P =.037 and P =.026, respectively), presence of lacune (P =.004 and P =.032, respectively), and severe LA (P =.002 and P =.008, respectively). However, MBs in strictly deep regions were significantly associated with higher mean arterial pressure (P =.030), and those in strictly lobar brain regions were significantly associated with older age (P =.023). Conclusions The risk factors of MBs in strictly deep or lobar regions differ modestly, which may be related to heterogeneous vascular pathologic changes.",,"Wang, Y.;Zhang, C.;Li, Z.;Zhao, X.;Wang, C.;Liu, L.;Pu, Y.;Zou, X.;Pan, Y.;Du, W.;Jing, J.;Wang, D.;Luo, Y.;Wong, K. S.",2015,1,,0,
450,Selective changes in white matter integrity in MCI and older adults with cognitive complaints,"BACKGROUND: White matter changes measured using diffusion tensor imaging have been reported in Alzheimer's disease and amnestic mild cognitive impairment, but changes in earlier pre-mild cognitive impairment stages have not been fully investigated. METHODS: In a cross-sectional analysis, older adults with mild cognitive impairment (n=28), older adults with cognitive complaints but without psychometric impairment (n=29) and healthy controls (n=35) were compared. Measures included whole-brain diffusion tensor imaging, T1-weighted structural magnetic resonance imaging, and neuropsychological assessment. Diffusion images were analyzed using Tract-Based Spatial Statistics. Voxel-wise fractional anisotropy and mean, axial, and radial diffusivities were assessed and compared between groups. Significant tract clusters were extracted in order to perform further region of interest comparisons. Brain volume was estimated using FreeSurfer based on T1 structural images. RESULTS: The mild cognitive impairment group showed lower fractional anisotropy and higher radial diffusivity than controls in bilateral parahippocampal white matter. When comparing extracted diffusivity measurements from bilateral parahippocampal white matter clusters, the cognitive complaint group had values that were intermediate to the mild cognitive impairment and healthy control groups. Group difference in diffusion tensor imaging measures remained significant after controlling for hippocampal atrophy. Across the entire sample, diffusion tensor imaging indices in parahippocampal white matter were correlated with memory function. CONCLUSIONS: These findings are consistent with previous results showing changes in parahippocampal white matter in Alzheimer's disease and mild cognitive impairment compared to controls. The intermediate pattern found in the cognitive complaint group suggests the potential of diffusion tensor imaging to contribute to earlier detection of neurodegenerative changes during prodromal stages. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.","Aged;Alzheimer Disease/diagnosis/pathology;Anisotropy;Atrophy;Brain/ pathology/physiology;Cognition Disorders/diagnosis/ pathology;Cross-Sectional Studies;Diffusion Magnetic Resonance Imaging/methods;Diffusion Tensor Imaging/methods;Female;Humans;Male;Memory/physiology;Mild Cognitive Impairment/diagnosis/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Wang, Y.;West, J. D.;Flashman, L. A.;Wishart, H. A.;Santulli, R. B.;Rabin, L. A.;Pare, N.;Arfanakis, K.;Saykin, A. J.",2012,Mar,10.1016/j.bbadis.2011.08.002,0,
451,Diffusion tensor imaging study of the temporal stem in Alzheimer's disease,"Objective: To study the changes of fractional anisotropy (FA) value of white matter of brain and temporal stem in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients as well as normal cognitive (NC) aged people with diffusion tensor imaging (DTI), and explore the damage mechanism of temporal stem and its diagnostic value on AD and aMCI. Methods: Ten patients with AD, 10 patients with aMCI and 10 NC volunteers as control group were scanned by routine MRI and DTI. FA values were calculated by post - processing software (DTIstudio) in temporal stem (including anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus), and white matter in anterior frontal, temperal, parietal and occipital lobes. The data were analyzed by SPSS 13.0. If bilateral differences of FA values were not statistically significant (P > 0.05), the average values of bilateral FA were selected and compared among 3 groups. If bilateral differences of FA values were statistically significant (P < 0.05), the measurement values were directly compared. Results: 1) There was no significant difference of FA values in bilateral symmetric white matter and temporal stem among AD, aMCI and NC groups (P > 0.05, for all). 2) There was significant difference of FA values in anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus between AD and aMCI groups (P < 0.05, for all). 3) There was significant difference of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal and parietal lobes between AD and NC groups (P < 0.05, for all). 4) There was no significant difference of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal lobe between aMCI and NC groups (P > 0.05, for all). Conclusions: The significant difference of FA values in temporal stem among AD, aMCI and NC groups suggests that temporal stem fiber bundles are of great significance in the white matter damage of AD, and DTI is helpful for the differential diagnosis of AD, aMCI and NC. The abnormal changes of",,"Wang, Y.;Li, K. C.",2014,1,,0,
452,Comparison of the clinical and magnetic resonance imaging characteristics of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy in mainland China and other countries,"Objectives: To analyse the clinical and MRI features of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in mainland China and compare these features with those reported in other countries. Methods: All 26 CADASIL families were collected in First Hospital of Peking University from January 2003 to October 2009, and the diagnosis was confirmed by ultrastructural examination or Notch3 gene analysis. The age of onset, initial symptoms, main symptoms in 102 patients were described and the features with those reported in Germany, Japan, Arab and France were compared using χ(2) test. The cranial MRI changes in 35 patients were analysed and compared with the British and French patients. Results: 102 patients had their initial symptoms between 22-80 years with the mean age of onset at (43.9 ± 11.0) years. There was no significant difference in the frequency of ischemic stroke or TIA (79.41%) between our patients and the patients.in other countries. Dementia rate (50.00%) was significantly greater than that of Arab (21.05%, χ(2)=5.513, P=0.020) and French patients (31.11%, χ(2)=4.517, P=0.034). The frequency of mood disturbances (14.71%) was significantly lower than that of German patients (30.39%, χ(2)=7.185, P=0.007). The frequency of migraine (13.73%) was similar to that of France but lower than that of Japan (40%, χ(2)=12.658, P=0.000), Germany (38.24%, χ(2)=15.932, P=0.000) and Arab (42.11%, χ(2)=6.869, P=0.009). Cranial MRIs were abnormal in all 35 patients, but no lesion was seen in the medulla oblongata Lacunar infarcts in the basal ganglia (82.86%) were significantly more frequent than that of French patients (60% χ(2)=5.663, P=0.017). The frequency of leukoaraiosis in the cerebrum was similar to that of French patients. Anterior temporal involvement (68.57%) was significantly lower than of British patients (95%, χ(2)=5.211, P=0.022). Conclusion: The clinical symptoms and MRI changes of CADASIL in different countries were not identical. Abnormal anterior temporal pole signal on MRI is not a sensitive marker for diagnosis of CADASIL in Chinese patients.",,"Wang, Y.;Hong, D. J.;Zhao, D. H.;Zhang, W.;Wang, Z. X.;Yuan, Y.",2010,October,,0,
453,"Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts","Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.","Aged;Aged, 80 and over;Algorithms;Cerebral Cortex/pathology;Cerebrovascular Disorders/ diagnosis;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Stroke/diagnosis;Stroke, Lacunar/ diagnosis","Wang, Y.;Catindig, J. A.;Hilal, S.;Soon, H. W.;Ting, E.;Wong, T. Y.;Venketasubramanian, N.;Chen, C.;Qiu, A.",2012,May 1,10.1016/j.neuroimage.2012.02.034,0,
454,Abnormal organization of white matter networks in patients with subjective cognitive decline and mild cognitive impairment,"Network analysis has been widely used in studying Alzheimer's disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD.","Aged;Brain Mapping;Case-Control Studies;Cognition Disorders/ pathology;Cognitive Dysfunction/ pathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Models, Biological;White Matter/ pathology;Pathology Section;amnestic mild cognitive impairment;network;subjective cognitive decline;white matter;interests.","Wang, X. N.;Zeng, Y.;Chen, G. Q.;Zhang, Y. H.;Li, X. Y.;Hao, X. Y.;Yu, Y.;Zhang, M.;Sheng, C.;Li, Y. X.;Sun, Y.;Li, H. Y.;Song, Y.;Li, K. C.;Yan, T. Y.;Tang, X. Y.;Han, Y.",2016,Aug 2,,0,455
455,Abnormal organization of white matter networks in patients with subjective cognitive decline and mild cognitive impairment,"Network analysis has been widely used in studying Alzheimer's disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD.",Pathology Section;amnestic mild cognitive impairment;diffusion tensor imaging;network;subjective cognitive decline;white matter,"Wang, X. N.;Zeng, Y.;Chen, G. Q.;Zhang, Y. H.;Li, X. Y.;Hao, X. Y.;Yu, Y.;Zhang, M.;Sheng, C.;Li, Y. X.;Sun, Y.;Li, H. Y.;Song, Y.;Li, K. C.;Yan, T. Y.;Tang, X. Y.;Han, Y.",2016,Jul 13,10.18632/oncotarget.10601,0,
456,Abnormal topological organization in white matter network in patients with amnestic mild cognitive impairment,"Objective: To investigate the characteristics of the topological architecture of structural brain networks using diffusion tensor imaging (DTI) in amnestic mild cognitive impairment (aMCI) patients and evaluate the value of quantitative complex network analysis in early diagnoses of Alzheimer' s disease. Methods: In this study, 26 aMCI patients and 30 age-matched normal controls, collected in memory clinics at Xuanwu Hospital of Capital Medical University from January 2011 to August 2014, underwent DTI. Fifty-six network matrices were constructed thresholding fractional anisotropy and fiber number. Finally relevant network parameters were compared between the two groups utilizing permutation test. Results: Both groups showed small-world architecture, whereas compared to normal controls, significant decrease in normalized clustering coefficient (for example, when threshold is 0.1, aMCI group was 2.47, normol control group was 2.57, P=0.049), local efficiency (aMCI group was 12.01, normol control group was 13.57, P=0.001) and small-world (aMCI group was 2.02, normol control group was 2.11, P=0.013) were found in aMCI, hut there was no significant difference in average degree (aMCI group was 92.02, normol control group was 103.62, P=0.502), normalized characteristic path length (aMCI group was 3.32, normol control group 3.62, P=0.061) and global efficiency (aMCI group was 1.23, normol control group 1.23, P=0.199) between the two groups. Conclusion: Our findings suggest that the structural network widely alters in aMCI patients and network analysis has the potential to be an imaging biomarker for aMCI diagnosis. (ClinicalTrials. gov Protocol Registration and Results System (NCT02353845))",,"Wang, X.;Zhang, M.;Li, Y.;Zeng, Y.;Sheng, C.;Hao, X.;Sun, Y.;Zhang, Y.;Li, H.;Yu, Y.;Li, X.;Chen, G.;Li, K.;Jia, J.;Tang, X.;Han, Y.",2015,8,,0,
457,How much do focal infarcts distort white matter lesions and global cerebral atrophy measures?,"BACKGROUND: White matter lesions (WML) and brain atrophy are important biomarkers in stroke and dementia. Stroke lesions, either acute or old, symptomatic or silent, are common in older people. Such stroke lesions can have similar signals to WML and cerebrospinal fluid (CSF) on magnetic resonance (MR) images, and may be classified accidentally as WML or CSF by MR image processing algorithms, distorting WML and brain atrophy volume from the true volume. We evaluated the effect that acute or old stroke lesions at baseline, and new stroke lesions occurring during follow-up, could have on measurement of WML volume, cerebral atrophy and their longitudinal progression. METHODS: We used MR imaging data from patients who had originally presented with acute lacunar or minor cortical ischaemic stroke symptoms, recruited prospectively, who were scanned at baseline and about 3 years later. We measured WML and CSF volumes (ml) semi-automatically. We manually outlined the acute index stroke lesion (ISL), any old stroke lesions present at baseline, and new lesions appearing de novo during follow-up. We compared baseline and follow-up WML volume, cerebral atrophy and their longitudinal progression excluding and including the acute ISL, old and de novo stroke lesions. A non-parametric test (Wilcoxon's signed rank test) was used to compare the effects. RESULTS: Among 46 patients (mean age 72 years), 33 had an ISL visible on MR imaging (median volume 2.05 ml, IQR 0.88-8.88) and 7 of the 33 had old lacunes at baseline: WML volume was 8.54 ml (IQR 5.86-15.80) excluding versus 10.98 ml (IQR 6.91-24.86) including ISL (p < 0.001). At follow-up, median 39 months later (IQR 30-45), 3 patients had a de novo stroke lesion; total stroke lesion volume had decreased in 11 and increased in 22 patients: WML volume was 12.17 ml (IQR 8.54-19.86) excluding versus 14.79 ml (IQR 10.02-38.03) including total stroke lesions (p < 0.001). Including/excluding lacunes at baseline or follow-up also made small differences. Twenty-two of the 33 patients had tissue loss due to stroke lesions between baseline and follow-up, resulting in a net median brain tissue volume loss (i.e. atrophy) during follow-up of 24.49 ml (IQR 12.87-54.01) excluding versus 24.61 ml (IQR 15.54-54.04) including tissue loss due to stroke lesions (p < 0.001). Including stroke lesions in the WML volume added substantial noise, reduced statistical power, and thus increased sample size estimated for a clinical trial. CONCLUSIONS: Failure to exclude even small stroke lesions distorts WML volume, cerebral atrophy and their longitudinal progression measurements. This has important implications for design and sample size calculations for observational studies and randomised trials using WML volume, WML progression or brain atrophy as outcome measures. Improved methods of discriminating between stroke lesions and WML, and between tissue loss due to stroke lesions and true brain atrophy are required.","Aged;Aged, 80 and over;Atrophy;Cerebral Infarction/diagnosis/ pathology;Dementia/pathology;Disease Progression;Follow-Up Studies;Humans;Image Processing, Computer-Assisted/methods;Longitudinal Studies;Magnetic Resonance Imaging/methods;Neurodegenerative Diseases/ pathology;Neuroimaging/methods","Wang, X.;Valdes Hernandez, M. C.;Doubal, F.;Chappell, F. M.;Wardlaw, J. M.",2012,,10.1159/000343226,0,
458,Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer's Disease: A Diffusion MRI Study with DTI and HARDI Models,"Alzheimer's disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.",,"Wang, T.;Shi, F.;Jin, Y.;Yap, P. T.;Wee, C. Y.;Zhang, J.;Yang, C.;Li, X.;Xiao, S.;Shen, D.",2016,,10.1155/2016/2947136,0,
459,The MRI findings of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy: One case report,,CADASIL;nuclear magnetic resonance imaging;short survey,"Wang, S. S.;Fan, G. G.",2011,,,0,
460,Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study,"BACKGROUND: Amide proton transfer (APT) imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging (MRI) in the field of molecular and cellular imaging. The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer's disease (AD) at 3.0 Tesla. METHODS: Twenty AD patients (9 men and 11 women; age range, 67-83 years) and 20 age-matched normal controls (11 men and 9 women; age range, 63-82 years) underwent APT and traditional MRI examination on a 3.0 Tesla MRI system. The magnetic resonance ratio asymmetry (MTR asym ) values at 3.5 ppm of bilateral hippocampi (Hc), temporal white matter regions, occipital white matter regions, and cerebral peduncles were measured on oblique axial APT images. MTR asym (3.5 ppm) values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test. Controlling for age, partial correlation analysis was used to investigate the associations between mini-mental state examination (MMSE) and the various MRI measures among AD patients. RESULTS: Compared with normal controls, MTR asym (3.5 ppm) values of bilateral Hc were significantly increased in AD patients (right 1.24% +/- 0.21% vs. 0.83% +/- 0.19%, left 1.18% +/- 0.18% vs. 0.80%+/- 0.17%, t = 3.039, 3.328, P = 0.004, 0.002, respectively). MTR asym (3.5 ppm) values of bilateral Hc were significantly negatively correlated with MMSE (right r = -0.559, P = 0.013; left r = -0.461, P = 0.047). CONCLUSIONS: Increased MTR asym (3.5 ppm) values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.",Aged;Alzheimer Disease/ diagnosis;Female;Humans;Magnetic Resonance Imaging/ methods;Male,"Wang, R.;Li, S. Y.;Chen, M.;Zhou, J. Y.;Peng, D. T.;Zhang, C.;Dai, Y. M.",2015,Mar 5,10.4103/0366-6999.151658,0,
461,Automatic segmentation and volumetric quantification of white matter hyperintensities on fluid-attenuated inversion recovery images using the extreme value distribution,"Introduction: This study aims to develop an automatic segmentation framework on the basis of extreme value distribution (EVD) for the detection and volumetric quantification of white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR) images. Methods: Two EVD-based segmentation methods, namely the Gumbel and Fréchet segmentation, were developed to detect WMHs on FLAIR (slice thickness = 5 mm; TR/TE/TI = 11,000/120/2,800 ms; flip angle = 90°) images. Another automatic segmentation method using a trimmed likelihood estimator (TLE) was implemented for comparison with our proposed segmentation framework. The performances of the three automatic segmentation methods were evaluated by comparing with the manual segmentation method. Results: The Dice similarity coefficients (DSCs) of the two EVD-based segmentation methods were larger than those of the TLE-based segmentation method (Gumbel, 0.823 ± 0.063; Fréchet, 0.843 ± 0.057; TLE, 0.817 ± 0.068), demonstrating that the EVD-based segmentation outperformed the TLE-based segmentation. The Fréchet segmentation obtained larger DSCs on patients with moderate to severe lesion loads and a comparable performance on patients with mild lesion loads, indicating that the Fréchet segmentation was superior to the Gumbel segmentation. The Gumbel segmentation underestimated the lesion volumes of all patients, whereas the Fréchet and TLE-based segmentation methods obtained overestimated lesion volumes (Manual, 13.71 ± 14.02 cc; Gumbel, 12.73 ± 13.21 cc; Fréchet, 13.88 ± 13.96 cc; TLE, 13.54 ± 12.27 cc). Moreover, the EVD-based segmentation was demonstrated to be comparable to other state-of-the-art methods on a publicly available dataset. Conclusion: The proposed EVD-based segmentation framework is a promising, effective, and convenient tool for volumetric quantification and further study of WMHs in aging and dementia.",,"Wang, R.;Li, C.;Wang, J.;Wei, X.;Li, Y.;Zhu, Y.;Zhang, S.",2015,2015,,0,
462,Automatic Segmentation and Quantitative Analysis of White Matter Hyperintensities on FLAIR Images Using Trimmed-Likelihood Estimator,"Rationale and Objectives: Quantitative analysis of white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR) images provides information for disease tracking, therapeutic efficacy assessment, and cognitive science research. This study developed an automatic segmentation method to detect and quantify WMHs on FLAIR images. This study aims to assess the accuracy and reproducibility of the proposed method. Materials and Methods: The FLAIR images of 82 patients (58-84 years) with different WMH burdens were acquired with the same 3T scanner (Intera-achieva SMI-2.1; Philip Medical System, Sixth Affiliated People's Hospital, Shanghai, China). The FLAIR images were preprocessed through brain extraction and intensity inhomogeneity correction. An anatomy atlas built from a set of 20 patients with different WMH burdens (mild, 11 patients; moderate, 6 patients; and severe, 3 patients) was used to estimate a control parameter in the framework of segmentation. The general flow for WMH segmentation included classification of foreground and background regions, detection of abnormally high signals, and WMH refinement. The performance of automatic segmentation was evaluated by a volumetric comparison with manual segmentation on patients with different WMH burdens. Results: Similarity index values for the accuracy of automatic segmentation compared to manual segmentation were consistently high for patients with different WMH burdens (mild, 0.78 ± 0.08; moderate, 0.83 ± 0.06; severe, 0.84 ± 0.08; and total, 0.80 ± 0.08). Linear regression demonstrated a strong correlation between the WMH volumes measured by the two methods in all patients (r = 0.98, P = .006). Small average differences were detected between the WMH volumes obtained through manual and automatic segmentations (mild, 4.76%; moderate, 6.84%; and severe, 7.59%). The results of Bland-Altman analysis show a system bias of 0.68 cm3 and a standard deviation of 2.10 cm3 over the range of 2.58-53.9 cm3. Conclusions: The developed method is accurate and efficient in detecting and quantifying differently sized WMHs on FLAIR images. Automatic segmentation is a promising computer-aided diagnostic tool to study WMHs in aging and dementia in basic research and even in clinical trials. © 2014 AUR.",white matter;quantitative analysis;model;human;patient;book;Even (people);psychology;linear regression analysis;nuclear magnetic resonance scanner;computer;diagnosis;hospital;therapy;classification;extraction;reproducibility;brain;basic research;China;aging;dementia;liquid;clinical trial (topic),"Wang, R.;Li, C.;Wang, J.;Wei, X.;Li, Y.;Hui, C.;Zhu, Y.;Zhang, S.",2014,,10.1016/j.acra.2014.07.001,0,
463,Automatic segmentation and quantitative analysis of white matter hyperintensities on FLAIR images using trimmed-likelihood estimator,"RATIONALE AND OBJECTIVES: Quantitative analysis of white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR) images provides information for disease tracking, therapeutic efficacy assessment, and cognitive science research. This study developed an automatic segmentation method to detect and quantify WMHs on FLAIR images. This study aims to assess the accuracy and reproducibility of the proposed method. MATERIALS AND METHODS: The FLAIR images of 82 patients (58-84 years) with different WMH burdens were acquired with the same 3T scanner (Intera-achieva SMI-2.1; Philip Medical System, Sixth Affiliated People's Hospital, Shanghai, China). The FLAIR images were preprocessed through brain extraction and intensity inhomogeneity correction. An anatomy atlas built from a set of 20 patients with different WMH burdens (mild, 11 patients; moderate, 6 patients; and severe, 3 patients) was used to estimate a control parameter in the framework of segmentation. The general flow for WMH segmentation included classification of foreground and background regions, detection of abnormally high signals, and WMH refinement. The performance of automatic segmentation was evaluated by a volumetric comparison with manual segmentation on patients with different WMH burdens. RESULTS: Similarity index values for the accuracy of automatic segmentation compared to manual segmentation were consistently high for patients with different WMH burdens (mild, 0.78 +/- 0.08; moderate, 0.83 +/- 0.06; severe, 0.84 +/- 0.08; and total, 0.80 +/- 0.08). Linear regression demonstrated a strong correlation between the WMH volumes measured by the two methods in all patients (r = 0.98, P = .006). Small average differences were detected between the WMH volumes obtained through manual and automatic segmentations (mild, 4.76%; moderate, 6.84%; and severe, 7.59%). The results of Bland-Altman analysis show a system bias of 0.68 cm(3) and a standard deviation of 2.10 cm(3) over the range of 2.58-53.9 cm(3). CONCLUSIONS: The developed method is accurate and efficient in detecting and quantifying differently sized WMHs on FLAIR images. Automatic segmentation is a promising computer-aided diagnostic tool to study WMHs in aging and dementia in basic research and even in clinical trials.","Aged;Aged, 80 and over;Algorithms;Brain/ pathology;Brain Diseases/ pathology;Female;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology","Wang, R.;Li, C.;Wang, J.;Wei, X.;Li, Y.;Hui, C.;Zhu, Y.;Zhang, S.",2014,Dec,10.1016/j.acra.2014.07.001,0,462
464,Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? A population-based study,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon4 allele. METHODS: This population-based study included 492 participants (age >/=60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. RESULTS: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon4 had no influential effect. CONCLUSION: The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.","Aged;Aged, 80 and over;Aging/ pathology;Apolipoproteins E/ genetics;Atrophy/pathology;Cardiovascular Diseases/ epidemiology;Cerebral Ventricles/ pathology;Female;Genotype;Gray Matter/ pathology;Hippocampus/ pathology;Humans;Leukoencephalopathies/epidemiology/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Sweden/epidemiology;White Matter/ pathology","Wang, R.;Fratiglioni, L.;Laveskog, A.;Kalpouzos, G.;Ehrenkrona, C. H.;Zhang, Y.;Bronge, L.;Wahlund, L. O.;Backman, L.;Qiu, C.",2014,Aug,10.1111/ene.12319,0,
465,Effects of vascular risk factors and APOE epsilon4 on white matter integrity and cognitive decline,"OBJECTIVE: To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people. METHODS: This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001-2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models. RESULTS: Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p < 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (ptrend < 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE epsilon4 allele interacted to negatively affect white matter microstructure; having multiple (>/=2) vascular factors was particularly detrimental to white matter integrity among APOE epsilon4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline. CONCLUSIONS: Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE epsilon4 carriers.","Aged;Aged, 80 and over;Apolipoprotein E4/ genetics;Cognition Disorders/diagnosis/ epidemiology/ genetics;Diffusion Tensor Imaging/trends;Female;Heterozygote;Humans;Male;Middle Aged;Population Surveillance/methods;Risk Factors;Sweden/epidemiology;Vascular Diseases/diagnosis/ epidemiology/ genetics;White Matter/ pathology","Wang, R.;Fratiglioni, L.;Laukka, E. J.;Lovden, M.;Kalpouzos, G.;Keller, L.;Graff, C.;Salami, A.;Backman, L.;Qiu, C.",2015,Mar 17,10.1212/wnl.0000000000001379,0,
466,Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: A population-based study,"Introduction The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear. Methods We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) ε4, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age ≥60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippocampus were assessed in the MRI sample. Results A higher FGCRS was associated with faster MMSE decline in young-old people (60–72 years) but not in old-old (≥78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P < .01); these associations were stronger among APOE ε4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline. Discussion The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.",apolipoprotein E4;biological marker;adult;aged;aging;allele;APOE epsilon4 gene;article;brain damage;brain size;brain ventricle;cardiovascular risk;cognitive defect;female;follow up;Framingham risk score;gray matter;hippocampus;human;major clinical study;male;Mini Mental State Examination;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;population research;priority journal;white matter;Intera,"Wang, R.;Fratiglioni, L.;Kalpouzos, G.;Lövdén, M.;Laukka, E. J.;Bronge, L.;Wahlund, L. O.;Bäckman, L.;Qiu, C.",2017,,10.1016/j.jalz.2016.06.2363,0,
467,Multiple diffusivities define white matter degeneration in amnestic mild cognitive impairment and Alzheimer's disease,"Different diffusivity measurements in diffusion-tensor imaging (DTI) could be helpful for detecting the distinct mechanisms of white matter degeneration in Alzheimer's disease (AD). However, few studies have explored the changes of white matter in amnestic mild cognitive impairment (aMCI) and AD by whole-brain voxel-wise analyses of all diffusivity indices. The association between grey matter atrophy and white matter damage measured by distinct diffusivities is still uncertain. Structural magnetic resonance imaging and DTI with four diffusivity indices, comprising fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, were performed in 30 normal controls, 26 mild AD patients, and 40 aMCI patients with isolated memory impairment. T1 voxel-based morphometry and DTI tract-based spatial statistics were applied to compare the grey and white matter changes in the 3 groups. In contrast to the lack of significant white matter change presenting in aMCI patients, extended white matter degeneration over entire cerebral networks was exhibited in mild AD patients. Both axonal degradation and demyelination contributed to the white matter degeneration in AD; nevertheless, demyelination essentially involved the frontal portion of cerebral networks. Axonal degradation and demyelination over the temporal region were associated with the contiguous grey matter atrophy. However, only the severity of demyelination over the frontal region was correlated with the degree of atrophy over adjacent frontal grey matter. Our results suggest that different mechanisms of white matter damage demonstrate discrete regional distribution in AD. Demyelination may independently correlate with contiguous grey matter over the frontal region.","Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/genetics/ pathology;Amnesia/epidemiology/genetics/ pathology;Apolipoproteins E/genetics;Cerebral Cortex/metabolism/pathology;Cerebrovascular Disorders/epidemiology/genetics/pathology;Demyelinating Diseases/epidemiology/genetics/pathology;Diffusion;Diffusion Tensor Imaging;Female;Humans;Leukoencephalopathies/epidemiology/genetics/ pathology;Male;Mild Cognitive Impairment/epidemiology/genetics/ pathology;Nerve Fibers, Myelinated/metabolism/pathology;Risk Factors","Wang, P. N.;Chou, K. H.;Lirng, J. F.;Lin, K. N.;Chen, W. T.;Lin, C. P.",2012,,10.3233/jad-2012-111304,0,
468,Cerebral Small Vessel Disease and Motoric Cognitive Risk Syndrome: Results from the Kerala-Einstein Study,"BACKGROUND: The contribution of cerebral small vessel disease to cognitive decline, especially in non-Caucasian populations, is not well established. OBJECTIVE: We examined the relationship between cerebral small vessel disease and motoric cognitive risk syndrome (MCR), a recently described pre-dementia syndrome, in Indian seniors. METHODS: 139 participants (mean age 66.6 +/- 5.4 y, 33.1% female) participating in the Kerala-Einstein study in Southern India were examined in a cross-sectional study. The presence of cerebral small vessel disease (lacunar infarcts and cerebral microbleeds (CMB)) and white matter hyperintensities on MRI was ascertained by raters blinded to clinical information. MCR was defined by the presence of cognitive complaints and slow gait in older adults without dementia or mobility disability. RESULTS: Thirty-eight (27.3% ) participants met MCR criteria. The overall prevalence of lacunar infarcts and CMB was 49.6% and 9.4% , respectively. Lacunar infarcts in the frontal lobe, but no other brain regions, were associated with MCR even after adjusting for vascular risk factors and presence of white matter hyperintensities (adjusted Odds Ratio (aOR): 4.67, 95% CI: 1.69-12.94). Frontal lacunar infarcts were associated with slow gait (aOR: 3.98, 95% CI: 1.46-10.79) and poor performance on memory test (beta: -1.24, 95% CI: -2.42 to -0.05), but not with cognitive complaints or non-memory tests. No association of CMB was found with MCR, individual MCR criterion or cognitive tests. CONCLUSIONS: Frontal lacunar infarcts are associated with MCR in Indian seniors, perhaps, by contributing to slow gait and poor memory function.",,"Wang, N.;Allali, G.;Kesavadas, C.;Noone, M. L.;Pradeep, V. G.;Blumen, H. M.;Verghese, J.",2016,Jan 12,10.3233/jad-150523,0,
469,Influence of leukoaraiosis on the cognition of patients with Parkinson disease,"OBJECTIVE: To explore the role of leukoaraiosis (LA) on the cognitive function in patients with Parkinson disease (PD). METHODS: The cohort for this study included 63 patients with PD, whom were divided into 3 groups according to cognitive status:with intact cognition (PD-IC, n = 23), with mild cognitive impairment (PD-MCI, n = 23) and with dementia (PDD, n = 17). All the patients were recruited from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between September 2011 and July 2012. The cognitive functions were evaluated by mini-metal state examination (MMSE), the Cambridge cognitive examination-Chinese version (CAMCOG-C), clinical dementia rating (CDR), clock drawing task (CDT) and verbal fluency test, etc. Depression symptoms were assessed by the geriatric depression scale (GDS) while motor symptoms by the Unified Parkinson's Disease Rating Scale-motor (UPDRS-motor) and the Hoehn and Yahr scale (HY). All the patients underwent magnetic resonance imaging (MRI) with a 3.0-T system. LA was rated using the semiquantitative visual rating system proposed by scheltens et al. RESULTS: Both the PD-IC (2.43 +/- 2.79) and PD-MCI (4.48 +/- 4.33) groups showed significantly lower deep hyperintensities (DHs) scores than the PDD group (7.88 +/- 6.69, P = 0.004 and 0.040, respectively), especially in frontal (1.09 +/- 1.31; 1.83 +/- 1.90; 3.24 +/- 2.64, P < 0.05) and parietal areas (0.09 +/- 0.29; 0.65 +/- 1.03; 1.53 +/- 2.32, P < 0.05). There were no significant differences in periventricular (1.57 +/- 1.75; 2.52 +/- 2.37; 3.24 +/- 2.64, P > 0.05), basal ganglia (0.09 +/- 0.42; 0.30 +/- 0.77; 0.53 +/- 1.33, P > 0.05) and infratentorial white matter hyperintensities scores (--; 0.13 +/- 0.63; 0.18 +/- 0.73, P > 0.05) among three groups. The DHs showed a significant correlation with age (P = 0.003), MMSE (P = 0.009), verbal fluency test (P = 0.009), orientation (P = 0.047) and executive function (P = 0.027) in CAMCOG-C. The multiple regression analysis showed that the MMSE scores were associated significantly with education (P < 0.001, beta = 0.600), DHs (P = 0.001, beta = -0.678) and HY (P = 0.035, beta = -0.480). DHs were the most significantly associated with MMSE scores. CONCLUSION: There was a significant correlation between DHs and multiple domain cognitive impairment in PD, especially in executive function. DHs, which were the most significantly variable associated with MMSE scores, may contribute to cognitive impairment in PD.","Adult;Aged;Aged, 80 and over;Cognition Disorders/ etiology;Dementia/psychology;Female;Humans;Leukoaraiosis/pathology/physiopathology/psychology;Male;Middle Aged;Neuropsychological Tests;Parkinson Disease/ physiopathology","Wang, L.;Zhu, X. Q.;Jiang, C. J.;Chen, X. W.;Sun, Z. W.",2013,Jan 15,,0,
470,Magnetic resonance spectroscopy in the diagnosis of cognitive impairment in AIDS patients,"BACKGROUND: The pathological abnormalities of the AIDS patients lie in the subcortical regions of the brain, specifically the deep white matter and basal ganglia, while the extent of pathology generally correlates with the severity of cognitive impairments in the white matter and basal ganglia. Brain metabolite changes of these lesions can reflect the pathological abnormalities. The purpose of this study was to assess the value of magnetic resonance spectroscopy (MRS) in the diagnosis of cognitive impairment in AIDS patients. METHODS: 3.0T MR was used to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatinine (Cr) in the frontal white matter, basal ganglia and parietal cortex of 21 AIDS patients with dementia complex (ADC), 19 AIDS patients with neuroasymptomatic (NAS) and 20 seronegative (SN) controls. Then we compared the difference of metabolic rate between AIDS patients and SN groups. RESULTS: NAA/Cr (mean = 1.2502, SD = 0.1600) was significantly decreased and Cho/Cr (mean = 1.2028, SD = 1.1655) was increased in the frontal white matter in ADC group, while NAA/Cr (mean = 1.5334, SD = 0.0513) was reduced in NAS group when compared with SN group. NAA/Cr in the basal ganglia was decreased in both ADC and NAS groups (mean = 1.2625, SD = 0.1615 and mean = 1.5278, SD = 0.0380, respectively). Cho/Cr (mean = 1.1631, SD = 0.0981) was markedly increased in ADC group. Although NAA/Cr, Cho/Cr and MI/Cr in the parietal cortex had a certain change in both ADC and NAS groups compared with SN group, the differences were not statistically significant. CONCLUSIONS: The brain metabolite changes of AIDS patients are correlated with cognitive impairments. MRS can be used as a valuable inspection method to assess cognitive impairments in AIDS patients.",Acquired Immunodeficiency Syndrome/*physiopathology;Adolescent;Adult;Cognition Disorders/*diagnosis;Female;Humans;Magnetic Resonance Imaging/*methods;Male;Young Adult,"Wang, L.;Shi, D. P.;Han, X.;Zhao, Q. X.;Yan, B.;Li, H. J.",2011,May,,0,
471,Alterations in cortical thickness and white matter integrity in mild cognitive impairment measured by whole-brain cortical thickness mapping and diffusion tensor imaging,"BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a risk factor for Alzheimer disease and can be difficult to diagnose because of the subtlety of symptoms. This study attempted to examine gray matter (GM) and white matter (WM) changes with cortical thickness analysis and diffusion tensor imaging (DTI) in patients with MCI and demographically matched comparison subjects to test these measurements as possible imaging markers for diagnosis. MATERIALS AND METHODS: Subjects with amnestic MCI (n = 10; age, 72.2 +/- 7.1 years) and normal cognition (n = 10; age, 70.1 +/- 7.7 years) underwent DTI and T1-weighted MR imaging at 3T. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cortical thickness were measured and compared between the MCI and control groups. We evaluated the diagnostic accuracy of 2 methods, either in combination or separately, using binary logistic regression and nonparametric statistical analyses for sensitivity, specificity, and accuracy. RESULTS: Decreased FA and increased ADC in WM regions of the frontal and temporal lobes and corpus callosum (CC) were observed in patients with MCI. Cortical thickness was decreased in GM regions of the frontal, temporal, and parietal lobes in patients with MCI. Changes in WM and cortical thickness seemed to be more pronounced in the left hemisphere compared with the right hemisphere. Furthermore, the combination of cortical thickness and DTI measurements in the left temporal areas improved the accuracy of differentiating MCI patients from control subjects compared with either measure alone. CONCLUSIONS: DTI and cortical thickness analyses may both serve as imaging markers to differentiate MCI from normal aging. Combined use of these 2 methods may improve the accuracy of MCI diagnosis.","Aged;Brain/ pathology;Cognition Disorders/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Nerve Fibers, Myelinated/ pathology;Sensitivity and Specificity","Wang, L.;Goldstein, F. C.;Veledar, E.;Levey, A. I.;Lah, J. J.;Meltzer, C. C.;Holder, C. A.;Mao, H.",2009,May,10.3174/ajnr.A1484,0,
472,White matter hyperintensities and changes in white matter integrity in patients with Alzheimer's disease,"INTRODUCTION: White matter hyperintensities (WMHs) are a risk factor for Alzheimer's disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. METHODS: Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D(R)), and axial diffusivity (D(A)) were analyzed using the region of interest and tract-based spatial statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. RESULTS: AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and D(R) were more sensitive measurements than MD and D(A) in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. CONCLUSIONS: WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. D(R) may serve as an imaging marker of myelin deficits associated with AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology","Wang, L.;Goldstein, F. C.;Levey, A. I.;Lah, J. J.;Meltzer, C. C.;Holder, C. A.;Mao, H.",2011,May,10.1007/s00234-010-0806-2,0,
473,"Diffusion tensor imaging measures of normal appearing white matter in patients who are aging, or have amnestic mild cognitive impairment, or Alzheimer's disease","To evaluate whether cerebral white matter integrity is related to cognitive function, and whether diffusion tensor imaging (DTI) could differentiate amnestic mild cognitive impairment (aMCI) from Alzheimer's disease (AD), 12 patients with AD, 12 with aMCI, and 12 controls were recruited for this study. Cognitive functions of all subjects were assessed using the Mini-Mental State Examination (MMSE) and AD Assessment Scale - Cognitive Subscale (ADAS-Cog). DTI studies were acquired, and fractional anisotropy (FA) and mean diffusivity (MD) values of normal-appearing white matter (NAWM) in multiple brain regions were obtained. Results showed that MMSE and ADAS-Cog subscores were significantly associated with white matter integrity of the temporal-parietal lobes. A decrease in FA values and an increase in MD values in multiple cortical regions were confirmed in patients with AD compared to controls. MD values in the posterior region of the corpus callosum in aMCI differed from those of early AD. Significant reductions of FA values in the NAWM of the parietal lobe was observed in aMCI compared to controls. Our data indicate that the microstructural white matter integrity in the temporal-parietal lobes is gradually impaired in the progressive process of AD, and that splenium MD values could be used as a biomarker differentiating aMCI from AD.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/diagnosis/ pathology;Amnesia/diagnosis/ pathology;Anisotropy;Biomarkers;Corpus Callosum/pathology;Diffusion Tensor Imaging/instrumentation/ methods;Female;Humans;Leukoencephalopathies/diagnosis/ pathology;Male;Middle Aged;Mild Cognitive Impairment/diagnosis/ pathology","Wang, J. H.;Lv, P. Y.;Wang, H. B.;Li, Z. L.;Li, N.;Sun, Z. Y.;Zhao, B. H.;Huang, Y.",2013,Aug,10.1016/j.jocn.2012.09.025,0,
474,Bipolar II disorder as the initial presentation of CADASIL: An underdiagnosed manifestation,"Mood disturbances have been documented in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The highly varied morbidity indicates that the affective symptoms in CADASIL have not been cataloged systematically, leading to ineffective treatment, affecting the patients’ quality of life, and possibly resulting in suicide. We present a case of CADASIL with bipolar II disorder as the first manifestation. A middle-aged female reported recurrent depressive episodes and appeared treatment resistant to adequate dosages and durations of antidepressants. Following a structured psychiatric interview and neuropsychological assessment, a past episode of hypomania was identified. Added treatment with sodium valproate alleviated most symptoms. Considering late-onset bipolar disorder with unexplained decline in cognition, a medical history of migraine, and a suspected family history of stroke, further cranial magnetic resonance imaging scan was performed and revealed severe leukoencephalopathy, prompting further investigation. The diagnosis was revised to CADASIL after Arg587Cys NOTCH3 mutation was confirmed. This case highlights the evolving process of affective disorder diagnosis and underlying organic etiologies. Based on the overlap of white matter hyperintensities, NOTCH3 mutation, and valproate therapy in bipolar disorder and CADASIL, bipolar II depression may be a poorly recognized manifestation of CADASIL. Well-designed clinical trials are warranted to verify the current findings.",arginine;cysteine;escitalopram;fluoxetine;Notch3 receptor;paroxetine;sertraline;valproic acid;adult;article;bipolar II disorder;CADASIL;case report;clinical feature;depression;disease severity;drug effect;female;gene mutation;human;hypomania;leukoencephalopathy;middle aged;neuroimaging;neuropsychological test;NOTCH3 gene;nuclear magnetic resonance imaging;treatment duration;white matter,"Wang, J.;Li, J.;Kong, F.;Lv, H.;Guo, Z.",2017,,10.2147/ndt.s142321,0,
475,Multi-modality magnetic resonance imaging features of cognitive function in mild cognitive impairment,"OBJECTIVE: To investigate the association of multi-modality neuroimaging features and cognitive function in mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: Nine individuals with amnestic MCI (aMCI), fifteen patients with mild probable AD, and eleven age-controlled cognitively normal controls (NC) were recruited. All participants were administered with mini-mental status examination (MMSE) and Cognitive assessment screening instrument (CASI) to assess general cognitive function. Optimized voxel-based morphometry (VBM) was used for the analysis with 3-D high resolution anatomical images. Values of fractional anisotropy (FA) and mean apparent diffusivity coefficient (ADC) were measured from different brain regions on diffusion-tensor images (DTI). The relationship between structural atrophy and DTI-based measurements in the selected brain regions was examined. RESULTS: The scores of MMSE and CASI were correlated with the volumetric changes in such areas as temporal, frontal and parietal lobes, and cingulate gyrus and hippocampal gyrus (P<0.001). The scores of MMSE and CASI were positively correlated with FA values, and negatively with ADC values in the white-matter-affected regions including temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus (P<0.05). CONCLUSIONS: Cognitive decline was associated with atrophy and white matter microstructural alterations in temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus in MCI and AD. Multi-modality imaging technique may be important in elucidating the brain mechanism of cognitive impairment.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology;Brain/ pathology;Case-Control Studies;Cognition Disorders/diagnosis/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged","Wang, H. L.;Yuan, H. S.;Su, L. M.;Zhu, Y.;Liao, J.;Zhang, M. Y.;Li, T.;Yu, X.",2010,Aug,,0,
476,"A learning-based wrapper method to correct systematic errors in automatic image segmentation: consistently improved performance in hippocampus, cortex and brain segmentation","We propose a simple but generally applicable approach to improving the accuracy of automatic image segmentation algorithms relative to manual segmentations. The approach is based on the hypothesis that a large fraction of the errors produced by automatic segmentation are systematic, i.e., occur consistently from subject to subject, and serves as a wrapper method around a given host segmentation method. The wrapper method attempts to learn the intensity, spatial and contextual patterns associated with systematic segmentation errors produced by the host method on training data for which manual segmentations are available. The method then attempts to correct such errors in segmentations produced by the host method on new images. One practical use of the proposed wrapper method is to adapt existing segmentation tools, without explicit modification, to imaging data and segmentation protocols that are different from those on which the tools were trained and tuned. An open-source implementation of the proposed wrapper method is provided, and can be applied to a wide range of image segmentation problems. The wrapper method is evaluated with four host brain MRI segmentation methods: hippocampus segmentation using FreeSurfer (Fischl et al., 2002); hippocampus segmentation using multi-atlas label fusion (Artaechevarria et al., 2009); brain extraction using BET (Smith, 2002); and brain tissue segmentation using FAST (Zhang et al., 2001). The wrapper method generates 72%, 14%, 29% and 21% fewer erroneously segmented voxels than the respective host segmentation methods. In the hippocampus segmentation experiment with multi-atlas label fusion as the host method, the average Dice overlap between reference segmentations and segmentations produced by the wrapper method is 0.908 for normal controls and 0.893 for patients with mild cognitive impairment. Average Dice overlaps of 0.964, 0.905 and 0.951 are obtained for brain extraction, white matter segmentation and gray matter segmentation, respectively.","Aged;Algorithms;Alzheimer Disease/pathology;Artificial Intelligence;Atlases as Topic;Brain/ anatomy & histology/pathology;Cerebral Cortex/ anatomy & histology/pathology;Databases, Factual;Female;Hippocampus/ anatomy & histology/pathology;Humans;Image Enhancement/methods;Image Processing, Computer-Assisted/ methods;Male;Middle Aged;Software","Wang, H.;Das, S. R.;Suh, J. W.;Altinay, M.;Pluta, J.;Craige, C.;Avants, B.;Yushkevich, P. A.",2011,Apr 1,10.1016/j.neuroimage.2011.01.006,0,
477,A novel cortical thickness estimation method based on volumetric Laplace-Beltrami operator and heat kernel,"Cortical thickness estimation in magnetic resonance imaging (MRI) is an important technique for research on brain development and neurodegenerative diseases. This paper presents a heat kernel based cortical thickness estimation algorithm, which is driven by the graph spectrum and the heat kernel theory, to capture the gray matter geometry information from the in vivo brain magnetic resonance (MR) images. First, we construct a tetrahedral mesh that matches the MR images and reflects the inherent geometric characteristics. Second, the harmonic field is computed by the volumetric Laplace-Beltrami operator and the direction of the steamline is obtained by tracing the maximum heat transfer probability based on the heat kernel diffusion. Thereby we can calculate the cortical thickness information between the point on the pial and white matter surfaces. The new method relies on intrinsic brain geometry structure and the computation is robust and accurate. To validate our algorithm, we apply it to study the thickness differences associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our preliminary experimental results on 151 subjects (51 AD, 45 MCI, 55 controls) show that the new algorithm may successfully detect statistically significant difference among patients of AD, MCI and healthy control subjects. Our computational framework is efficient and very general. It has the potential to be used for thickness estimation on any biological structures with clearly defined inner and outer surfaces.","Aged;Algorithms;Alzheimer Disease/ pathology;Cerebral Cortex/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/ pathology;Organ Size;Reproducibility of Results;Sensitivity and Specificity","Wang, G.;Zhang, X.;Su, Q.;Shi, J.;Caselli, R. J.;Wang, Y.",2015,May,10.1016/j.media.2015.01.005,0,
478,Novel compound heterozygous mutations causing Kufs disease type B,"Background: Kufs disease type B (also termed CLN13), an adult-onset form of neuronal ceroid lipofuscinosis (NCL), is genetically heterogeneous and challenging to diagnose. Recently, mutations in cathepsin-F have been identified as the causative gene for autosomal recessive Kufs disease type B. Results: Here, we report a sporadic case of Kufs disease type B with novel compound heterozygous mutations, a novel missense mutation c.977G>T (p.C326F) and a novel nonsense mutation c.416C>A (p.S139X), in the cathepsin-F gene. The magnetic resonance imaging findings were consistent with those demonstrated in adult neuronal ceroid lipofuscinosis: diffuse cortical atrophy, mild hyperintensity and reduction of the deep white matter on T2-weighted images. A skin biopsy was negative for abnormalities. Conclusions: Altogether, our findings broaden the mutation database in relation to the neuronal ceroid lipofuscinosis, and the clinical diagnosis of Kufs disease type B was confirmed.",brain cortex atrophy;case report;congenital malformation;diagnosis;gene frequency;heterozygosity;human;missense mutation;neuronal ceroid lipofuscinosis;nonsense mutation;nuclear magnetic resonance imaging;skin biopsy;white matter;cathepsin F;endogenous compound,"Wang, C.;Xu, H.;Yuan, Y.;Lian, Y.;Xie, N.;Ming, L.",2017,,10.1080/00207454.2017.1403439,0,
479,Atrophy and dysfunction of parahippocampal white matter in mild Alzheimer's disease,"In addition to atrophy of mesial temporal lobe structures critical for memory function, white matter projections to the hippocampus may be compromised in individuals with mild Alzheimer's disease (AD), thereby compounding the memory difficulty. In the present study, high-resolution structural imaging and diffusion tensor imaging techniques were used to examine microstructural alterations in the parahippocampal white matter (PWM) region that includes the perforant path. Results demonstrated white matter volume loss bilaterally in the PWM in patients with mild AD. In addition, the remaining white matter had significantly lower fractional anisotropy and higher mean diffusivity values. Both increased mean diffusivity and volume reduction in the PWM were associated with memory performance and ApoE epsilon4 allele status. These findings indicate that, in addition to partial disconnection of the hippocampus from incoming sensory information due to volume loss in PWM, microstructural alterations in remaining fibers may further degrade impulse transmission to the hippocampus and accentuate memory dysfunction. The results reported here also suggest that ApoE epsilon4 may exacerbate PWM changes.","Aged;Aged, 80 and over;Aging/genetics/pathology;Alleles;Alzheimer Disease/genetics/ pathology/psychology;Anisotropy;Apolipoprotein E4/genetics;Atrophy;Corpus Callosum/ pathology;Diffusion Tensor Imaging/ methods;Female;Hippocampus/ pathology;Humans;Male;Memory;Nerve Fibers, Myelinated/ pathology/physiology;Synaptic Transmission","Wang, C.;Stebbins, G. T.;Medina, D. A.;Shah, R. C.;Bammer, R.;Moseley, M. E.;deToledo-Morrell, L.",2012,Jan,10.1016/j.neurobiolaging.2010.01.020,0,
480,Adult metachromatic leukodystrophy. Value of computed tomographic scanning and magnetic resonance imaging of the brain,"Patients with adult-onset metachromatic leukodystrophy (MLD) often present with personality changes or deterioration of cognitive functions. Although rare, this form of MLD should be included in the differential diagnosis of psychotic and dementing disorders. The following case report describes a 38-year-old man with adult-onset MLD, who carried the diagnosis of schizophrenia and was treated as a schizophrenic for a number of years. Metachromatic leukodystrophy was initially suspected because of white matter abnormalities detected on computed tomographic scans and magnetic resonance images of the brain. The diagnosis of MLD was confirmed by the discovery of markedly reduced leukocyte arylsulfatase A activity. The computed tomographic and magnetic resonance imaging findings in MLD are reviewed.",,"Waltz, G.;Harik, S. I.;Kaufman, B.",1987,1987,,0,
481,Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults,"Previous studies have indicated a decreased risk for developing Alzheimer's disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.","Aged;Aged, 80 and over;Aging/*drug effects/pathology;Analysis of Variance;Anti-Inflammatory Agents/*adverse effects/classification;Arizona;Arthritis/drug therapy/*pathology;Brain/*drug effects/pathology;*Brain Mapping;Case-Control Studies;Female;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Middle Aged","Walther, K.;Bendlin, B. B.;Glisky, E. L.;Trouard, T. P.;Lisse, J. R.;Posever, J. O.;Ryan, L.",2011,Mar,10.1016/j.neurobiolaging.2009.03.006,0,
482,Transient ischaemic attacks are associated with increased rates of global cerebral atrophy,"Objectives: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group. Methods: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls. Results: 22 patients (37%) developed new ""clinically silent"" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001). Conclusions: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome.",,"Walters, R. J. L.;Fox, N. C.;Schott, J. M.;Crum, W. R.;Stevens, J. M.;Rossor, M. N.;Thomas, D. J.",2003,1,,0,
483,Schizophrenia-like psychosis and aceruloplasminemia,"Schizophrenia-like illnesses occur in a variety of medical and neurological conditions but to date have not been described in association with aceruloplasminemia. Aceruloplasminemia is an autosomal recessive disorder of iron metabolism which leads to iron deposition in the basal ganglia, thalamus, cerebellum and hippocampus and which usually presents in middle age with extrapyramidal symptoms and dementia. We describe a 21-year-old woman on treatment for aceruloplasminemia who presented with schizophrenia-like psychosis and declining function in the absence of neurological signs. Neuropsychological testing showed significant dominant hemisphere deficits. Magnetic resonance imaging showed bilateral iron deposition in the cerebellar dentate nuclei and thalami, frontal atrophy, and periventricular white matter hyperintensities. Functional imaging suggested global hypoperfusion. The clinical, cognitive and imaging findings were not typical for either aceruloplasminemia or schizophrenia alone and the possible relationship between the two disorders is discussed with particular reference to implications for our understanding of schizophrenia.",,"Walterfang, M.;March, E.;Varghese, D.;Miller, K.;Simpson, L.;Tomlinson, B.;Velakoulis, D.",2006,Dec,,0,
484,Shape analysis of the corpus callosum in Alzheimer's disease and frontotemporal lobar degeneration subtypes,"Morphology of the corpus callosum is a useful biomarker of neuronal loss, as different patterns of cortical atrophy help to distinguish between dementias such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). We used a sophisticated morphometric analysis of the corpus callosum in FTLD subtypes including frontotemporal dementia (FTD), semantic dementia (SD), and progressive non-fluent aphasia (PNFA), and compared them to AD patients and 27 matched controls. FTLD patient subgroups diverged in their callosal morphology profiles, with FTD patients showing marked widespread differences, PNFA patients with differences largely in the anterior half of the callosum, and SD patients differences in a small segment of the genu. AD patients showed differences in predominantly posterior callosal regions. This study is consistent with our previous findings showing significant cortical and subcortical regional atrophy across FTLD subtypes, and suggests that callosal atrophy patterns differentiate AD from FTLD, and FTLD subtypes.",Aged;Alzheimer Disease/*pathology;Corpus Callosum/*pathology;Female;Frontotemporal Lobar Degeneration/*classification/*pathology;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Retrospective Studies;Alzheimer's disease;corpus callosum;frontotemporal dementia;white matter,"Walterfang, M.;Luders, E.;Looi, J. C.;Rajagopalan, P.;Velakoulis, D.;Thompson, P. M.;Lindberg, O.;Ostberg, P.;Nordin, L. E.;Svensson, L.;Wahlund, L. O.",2014,,10.3233/jad-131853,0,
485,"Symptoms, vascular risk factors and blood-brain barrier function in relation to CT white-matter changes in dementia","The aim was to study the frequently found white-matter changes on computerized tomography (CT) in patients with dementia and to relate these changes to clinical regional brain symptomatology, vascular factors, albumin ratio [indicator of blood-brain barrier (BBB) function] and other CT changes. The study included 85 patients, average age 71 ± 8, with Alzheimer's disease (n = 56) and vascular dementia (n = 29), who underwent CT (Siemens Somatome DR 1) of the brain. They were inpatients in a psychiatric department specialized in dementia investigations. The degree of CT white-matter changes (absence, mild-moderate, severe) was the basis for the division of the patients into three groups. As the patients without white-matter changes were significantly younger than those with such changes, all statistical analyses were controlled for age. Subcortical symptomatology was significantly more frequent in the group with severe white-matter changes, whereas the reverse was true for parietal symptomatology. Diabetes mellitus, hypertension, ischemic cardiac disease and lacunas were significantly more common in patients with white-matter changes, whereas the freqeuncy of transient ischemic attack/stroke episodes did not differ significantly between the groups. The albumin ratio was significantly higher in the groups with white-matter changes and highest in the group with severe white-matter changes. The findings indicate that white-matter changes in demented patients are at least partially an age- and stroke-independent disease manifestation of the vascular system and is associated with a specific symptom pattern. BBB dysfunction may be the link between the vasculature and the tissue damage. Copyright (C) 2000 S. Karger AG, Basel.",adult;aged;Alzheimer disease;article;blood brain barrier;blood vessel injury;computer assisted tomography;dementia;diabetes mellitus;female;human;hypertension;ischemic heart disease;major clinical study;male;multiinfarct dementia;priority journal;risk factor;scoring system;statistical analysis;tissue injury;white matter,"Wallin, A.;Sjögren, M.;Edman, Å;Blennow, K.;Regland, B.",2000,,,0,
486,Cerebrospinal fluid cytoskeleton proteins in patients with subcortical white-matter dementia,"The cerebrospinal fluid (CSF) levels of two cytoskeleton proteins, tau and the light subunit of neurofilament protein (NFL), both considered to reflect cerebral white-matter components, were investigated in a group of patients with a subtype of vascular dementia called 'subcortical white-matter dementia' (SWD). The group consisted of 25 demented patients with frontosubcortical brain syndromes, white-matter changes on computed tomography or magnetic resonance imaging and vascular disease or pronounced vascular risk factors. CSF-NFL was increased, whereas CSF-tau was normal, suggesting a differential involvement of the cytoskeleton in this patient group. The albumin ratio and the apolipoproteinE4 (ApoE4) allele status were also investigated. The albumin ratio was increased, indicating damage to the vessel walls with breakdown of the blood-brain barrier. No relationship was found between ApoE4 alleles and CSF levels of tau or NFL in this patient group. Besides presenting original data, the disease status of SWD is also discussed.","Aged;Aged, 80 and over;Cytoskeletal Proteins/cerebrospinal fluid;Dementia, Vascular/ cerebrospinal fluid;Female;Humans;Male;Middle Aged;Neurofilament Proteins/ cerebrospinal fluid;tau Proteins/ cerebrospinal fluid","Wallin, A.;Sjogren, M.",2001,Nov,,0,
487,White matter low attenuation on computed tomography in Alzheimer's disease and vascular dementia - Diagnostic and pathogenetic aspects,"Demented patients with early-onset Alzheimer's disease (AD) (n = 17), late-onset Alzheimer's disease (n = 30) and vascular dementia (VD) (n = 20) were studied with computed tomography of the brain. Semiquantitative evaluation of white matter low attenuation (WMLA) and central and cortical atrophy was performed without knowledge of the clinical diagnosis. In early onset AD there was almost complete absence of WMLA and central atrophy compared with the other groups, which showed moderate to severe changes. This suggests that early-onset AD should be separated from the late-onset form. The increased systolic blood pressure found in the WMLA group supports the opinion that WMLA has a vascular origin. The high percentage of WMLA in VD and late-onset AD indicates that subcortical factors have to be considered in the pathogenesis of these disorders.",adult;aged;Alzheimer disease;article;brain atrophy;computer analysis;computer assisted tomography;female;human;male;methodology;multiinfarct dementia;priority journal;white matter,"Wallin, A.;Blennow, K.;Uhlemann, C.;Langstrom, G.;Gottfries, C. G.",1989,,,0,
488,Subtype identification in vascular dementia. An important step towards more precise diagnosis and improved treatment,"Until 1970, the definition of vascular dementia was unspecific and resulted in overdiagnosis of ""atherosclerosis"". It was replaced by an oversimplified definition based on the notion that vascular dementia is practically always a result of infarctions. However, since the beginning of the 1990s, the concept of vascular dementia has undergone re-evaluation. With the aid of brain imaging, the existence has been demonstrated of circulation-related cerebral tissue changes other than infarcts. It is now clear that vascular dementia is a heterogeneous entity possible to subtype. One of the subtypes is subcortical white-matter dementia, which is perhaps more common than multi-infarct dementia. Subtype identification is a useful aid to reliable diagnosis, and in the long run it may prove helpful in improving treatment.",,"Wallin, A.",1995,6,,0,
489,"Is There an Association of Physical Activity with Brain Volume, Behavior, and Day-to-day Functioning? A Cross Sectional Design in Prodromal and Early Huntington Disease","BACKGROUND: Huntington disease (HD) is a genetic neurodegenerative disease leading to progressive motor, cognitive, and behavioral decline. Subtle changes in these domains are detectable up to 15 years before a definitive motor diagnosis is made. This period, called prodromal HD, provides an opportunity to examine lifestyle behaviors that may impact disease progression. THEORETICAL FRAMEWORK: Physical activity relates to decreased rates of brain atrophy and improved cognitive and day-to-day functioning in Alzheimer disease and healthy aging populations. Previous research has yielded mixed results regarding the impact of physical activity on disease progression in HD and paid little attention to the prodromal phase. METHODS: We conducted analyses of associations among current physical activity level, current and retrospective rate of change for hippocampus and striatum volume, and cognitive, motor, and day-to-day functioning variables. Participants were 48 gene-expanded cases with prodromal and early-diagnosed HD and 27 nongene-expanded control participants. Participants wore Fitbit Ultra activity monitors for three days and completed the self-reported International Physical Activity Questionnaire (IPAQ). Hippocampal and striatal white matter volumes were measured using magnetic resonance imaging. Cognitive tests included the Stroop Color and Word Test, and the Symbol Digit Modalities Test (SDMT). Motor function was assessed using the Unified Huntington's Disease Rating Scale total motor score (TMS). Day-to-day functioning was measured using the World Health Organization Disability Assessment Schedule (WHODAS) version 2.0. RESULTS: Higher Fitbit activity scores were significantly related to better scores on the SDMT and WHODAS in case participants but not in controls. Fitbit activity scores tracked better with TMS scores in the group as a whole, though the association did not reach statistical significance in the case participants. Higher Fitbit activity scores related to less day-to-day functioning decline in retrospective slope analyses. Fitbit activity scores did not differ significantly between cases and controls. CONCLUSIONS: This is the first known study examining the associations between activity level and imaging, motor, cognitive, and day-to-day functioning outcomes in prodromal and early HD. Preliminary results suggest physical activity positively correlates with improved cognitive and day-to-day functioning and possibly motor function in individuals in the prodromal and early phase of the condition.",,"Wallace, M.;Downing, N.;Lourens, S.;Mills, J.;Kim, J. I.;Long, J.;Paulsen, J.;Predict-Hd, Investigators;Coordinators Of The Huntington Study, Group",2016,Mar 17,,0,
490,Interactive relations of blood pressure and age to subclinical cerebrovascular disease,"OBJECTIVE: To examine interactive relations of blood pressure (BP) and age to MRI indices of subclinical cerebrovascular disease in middle-aged to older adults. METHODS: One hundred and thirteen stroke-free and dementia-free, community-dwelling adults (ages 54-81 years; 65% men; 91% white) engaged in (1) clinical assessment of resting SBP and DBP; (2) MRI rated for periventricular white matter hyperintensities (WMH) and deep WMH silent brain infarction (SBI) and brain atrophy (i.e. ventricular enlargement and sulcal widening ). Principal components analysis of the MRI ratings yielded a two-component solution--(1) periventricular and deep WMH SBI; and (2) ventricular enlargement, sulcal widening. RESULTS: Relations of SBP, DBP and pulse pressure (PP) (and their interactions with age) to each MRI component were examined in multiple regression analyses adjusted for age, sex, fasting plasma glucose and cholesterol, and antihypertensives. For component 1, results indicated significant interactions of SBP and PP with age (P < 0.05); higher levels of SBP and PP were associated with greater white matter disease and brain infarction at younger ages (</= 68 years). Significant interactions of SBP and DBP with age were also noted for component 2 (P < 0.05); higher levels of BP were associated with greater brain atrophy at younger ages (</= 63 years). CONCLUSION: : Higher BP and PP are associated with greater subclinical cerebrovascular disease most prominently in the 'young old'. Appropriate management of hypertension and arterial stiffening may be critical to the preservation of brain structure with ageing.","Aged;Aged, 80 and over;Aging/*physiology;Blood Pressure/*physiology;Cerebrovascular Disorders/diagnosis/*epidemiology/*pathology;Cross-Sectional Studies;Female;Humans;Incidence;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Regression Analysis;Risk Factors","Waldstein, S. R.;Wendell, C. R.;Lefkowitz, D. M.;Siegel, E. L.;Rosenberger, W. F.;Spencer, R. J.;Manukyan, Z.;Katzel, L. I.",2012,Dec,10.1097/HJH.0b013e3283595651,0,
491,Differential Associations of Socioeconomic Status With Global Brain Volumes and White Matter Lesions in African American and White Adults: the HANDLS SCAN Study,"OBJECTIVE: The aim of the study was to examine interactive relations of race and socioeconomic status (SES) to magnetic resonance imaging (MRI)-assessed global brain outcomes with previously demonstrated prognostic significance for stroke, dementia, and mortality. METHODS: Participants were 147 African Americans (AAs) and whites (ages 33-71 years; 43% AA; 56% female; 26% below poverty) in the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN substudy. Cranial MRI was conducted using a 3.0 T unit. White matter (WM) lesion volumes and total brain, gray matter, and WM volumes were computed. An SES composite was derived from education and poverty status. RESULTS: Significant interactions of race and SES were observed for WM lesion volume (b = 1.38; eta = 0.036; p = .028), total brain (b = 86.72; eta = 0.042; p < .001), gray matter (b = 40.16; eta = 0.032; p = .003), and WM (b = 46.56; eta = 0.050; p < .001). AA participants with low SES exhibited significantly greater WM lesion volumes than white participants with low SES. White participants with higher SES had greater brain volumes than all other groups (albeit within normal range). CONCLUSIONS: Low SES was associated with greater WM pathology-a marker for increased stroke risk-in AAs. Higher SES was associated with greater total brain volume-a putative global indicator of brain health and predictor of mortality-in whites. Findings may reflect environmental and interpersonal stressors encountered by AAs and those of lower SES and could relate to disproportionate rates of stroke, dementia, and mortality.",,"Waldstein, S. R.;Dore, G. A.;Davatzikos, C.;Katzel, L. I.;Gullapalli, R.;Seliger, S. L.;Kouo, T.;Rosenberger, W. F.;Erus, G.;Evans, M. K.;Zonderman, A. B.",2017,Apr,,0,
492,Regional brain metabolite abnormalities in inherited prion disease and asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic resonance spectroscopy,"Introduction: Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Methods: We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. Results: One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z =5.3). Conclusion: Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease. © Springer-Verlag 2006.",,"Waldman, A. D.;Cordery, R. J.;MacManus, D. G.;Godbolt, A.;Collinge, J.;Rossor, M. N.",2006,June,,0,
493,"High resolution SPECT with [99mTc]-d,l-HMPAO in normal pressure hydrocephalus before and after shunt operation","Cranial CT and high resolution measurements of regional cerebral blood flow (rCBF) with brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethylpropyleneamine oxime ([99mTc]-d,l-HMPAO) were performed before and after shunt operation in 14 consecutive patients with dementia and normal pressure hydrocephalus (NPH). When compared with a control group of 14 age matched healthy volunteers, the group of NPH patients was characterised by an enlarged subcortical low-flow region, significantly reduced rCBF and enhanced side-to-side asymmetry of rCBF in the central white matter, and enhanced side-to-side asymmetry in the inferior and mid-temporal cortex. Global CBF was normal. Shunt operation reduced the mean area of the ventricles on CT and of the subcortical low-flow region on SPECT. Global CBF was unchanged. All 14 patients had an abnormal pre-shunt rCBF pattern with enlargement of the subcortical low flow region, focal cortical blood flow deficits, or both. Shunt operation improved the clinical status in 11 patients, and the area of the subcortical low flow region correctly classified 3/3 unimproved and 10/11 improved patients. Shunt operation normalised or reduced the area of the subcortical low flow region in nine of 10 patients. It is concluded that SPECT with [99mTc]-d,l-HMPAO is a useful supplement in the diagnosis of NPH versus normal ageing, and that SPECT may help to identify patients not likely to benefit clinically from surgery.","Adult;Aged;Aged, 80 and over;Brain/physiopathology/*radionuclide imaging/surgery;*Cerebrospinal Fluid Shunts;Cerebrovascular Circulation/physiology;Female;Humans;Hydrocephalus, Normal Pressure/physiopathology/*radionuclide imaging/surgery;Male;Middle Aged;*Organotechnetium Compounds;*Oximes;Prognosis;Technetium Tc 99m Exametazime;Time Factors;Tomography, Emission-Computed, Single-Photon","Waldemar, G.;Schmidt, J. F.;Delecluse, F.;Andersen, A. R.;Gjerris, F.;Paulson, O. B.",1993,Jun,,0,
494,White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates,"In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy control subjects, all without major cerbrovascular risk factors. The 133Xe inhalation method and the [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) technique with single photon emission computed tomography (SPECT) were used to measure rCBF. Rating scores for PVHs were significantly higher in the Alzheimer's disease group (p < 0.01) and correlated significantly with the volume of ventricles (p < 0.05) and with systolic arterial blood pressure (p < 0.01), but not with rCBF. By contrast, there was no significant difference in the rating scores or volumes of DWMHs between the two groups, although three patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p < 0.001), but not with frontal, temporal, parietal, or occipital rCBF. Postmortem histopathology of extensive DWMH lesions in one patient with definite Alzheimer's disease showed a partial loss of myelin and astrocytic gliosis, but no ischaemic changes. It is concluded that DWMH lesions may be associated with reduced rCBF in the hippocampal region. The heterogenous topography of neocortical rCBF deficits in Alzheimer's disease could not be explained by deafferentation from underlying white matter hyperintensities and therefore may reflect variations in the topography of cortical abnormalities.","Aged;Aged, 80 and over;Alzheimer Disease/complications/diagnosis/*pathology/*physiopathology;Blood Flow Velocity;Blood Pressure;Case-Control Studies;Cerebral Ventricles/*blood supply/*pathology;*Cerebrovascular Circulation;Dementia/*etiology;Female;Hippocampus/blood supply/pathology;Humans;*Magnetic Resonance Imaging;Male;Matched-Pair Analysis;Middle Aged;Organotechnetium Compounds;Oximes;Prospective Studies;Regional Blood Flow;Severity of Illness Index;Systole;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon;Xenon Radioisotopes","Waldemar, G.;Christiansen, P.;Larsson, H. B.;Hogh, P.;Laursen, H.;Lassen, N. A.;Paulson, O. B.",1994,Dec,,0,
495,Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain,"Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 +/- 0.55 vs 1.64 +/- 0.22; parietal, 2.50 +/- 0.52 vs 1.74 +/- 0.22; posterior cingulate, 2.84 +/- 0.59 vs 1.73 +/- 0.22; and WM in the centrum semiovale, 2.21 +/- 0.53 vs 2.42 +/- 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.",11C-PiB-PET;Alzheimer's disease;Amyloid deposit;Dementia;White matter,"Wakabayashi, Y.;Ishii, K.;Hosokawa, C.;Hyodo, T.;Kaida, H.;Yamada, M.;Yagyu, Y.;Tsurusaki, M.;Kozuka, T.;Sugimura, K.;Murakami, T.",2017,Mar 13,,0,
496,Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study,"Current definitions for the preclinical phase of dementia focus predominantly on cognitive measures, with particular emphasis on memory and the prediction of Alzheimer's disease. Incorporation of non-cognitive, clinical markers into preclinical definitions may improve their predictive power. The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling participants aged 75 or over at recruitment. At baseline, participants were defined as demented, cognitively intact or having a syndrome possibly representing the preclinical phase of Alzheimer's disease, vascular dementia, an extrapyramidal dementia or various combinations of the three. Those with cognitive impairment in combination with gait and motor slowing were the most likely to dement over the 6-year period (OR 5.6; 95% CI 2.5-12.6). This group was also the most likely to die (OR 3.3; 95% CI 1.6-6.9). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Simple measures of gait may provide useful clinical tools, assisting in the prediction of dementia. However, the underlying nature of these deficits is not yet known.","Aged;Alzheimer Disease/pathology;Basal Ganglia Diseases/pathology;Dementia, Vascular/epidemiology/pathology/*physiopathology;Disease Progression;Female;Gait/*physiology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;New South Wales/epidemiology;Odds Ratio;Predictive Value of Tests","Waite, L. M.;Grayson, D. A.;Piguet, O.;Creasey, H.;Bennett, H. P.;Broe, G. A.",2005,Mar 15,10.1016/j.jns.2004.11.009,0,
497,Tract-based spatial statistics: application to mild cognitive impairment,"RATIONALE AND OBJECTIVES: The primary objective of the current investigation was to characterize white matter integrity in different subtypes of mild cognitive impairment (MCI) using tract-based spatial statistics of diffusion tensor imaging. MATERIALS AND METHODS: The study participants were divided into 4 groups of 30 subjects each as follows: cognitively healthy controls, amnestic MCI, dysexecutive MCI, and Alzheimer's disease (AD). All subjects underwent a comprehensive neuropsychological assessment, apolipoprotein E genotyping, and 3-tesla MRI. The diffusion tensor was reconstructed and then analyzed using tract-based spatial statistics. The changes in brain white matter tracts were also examined according to the apolipoprotein E epsilon 4 status. RESULTS: Compared with controls, amnestic MCI patients showed significant differences in the cerebral white matter, where changes were consistently detectable in the frontal and parietal lobes. We found a moderate impact of the apolipoprotein E epsilon 4 status on the extent of white matter disruption in the amnestic MCI group. Patients with AD exhibited similar but more extensive alterations, while no significant changes were observed in dysexecutive MCI patients. CONCLUSION: The results from this study indicate that amnestic MCI is the most likely precursor to AD as both conditions share significant white matter damage. By contrast, dysexecutive MCI seems to be characterized by a distinct pathogenesis.","Aged;Aged, 80 and over;Alzheimer Disease/genetics/pathology;Apolipoprotein E4/genetics;Diffusion Tensor Imaging/methods;Female;Genotype;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mild Cognitive Impairment/genetics/ pathology;Neuropsychological Tests;White Matter/ pathology","Wai, Y. Y.;Hsu, W. C.;Fung, H. C.;Lee, J. D.;Chan, H. L.;Tsai, M. L.;Lin, Y. C.;Wu, Y. R.;Ying, L.;Wang, J. J.",2014,,10.1155/2014/713079,0,
498,,"New guidelines on care in dementia from the Swedish National Board of Health and Welfare emphasize that brain imaging should be included in the standard diagnostic evaluation. Evidence supports the importance of regional/global atrophy and white matter changes in dementia. However, the use of imaging in dementia evaluation is often sub-optimal, urging optimization of clinical imaging practice. Imaging Cognitive Impairment Network (ICINET) is a network between some of the largest Swedish and Norwegian university hospitals. The network's aims are to standardize the radiological evaluation and reporting of structural MRI/CT and to propose a suitable MRI protocol, which has the potential to be harmonized across sites. The importance of efficient clinical imaging practice in dementia will continue to increase with increasing numbers of dementia investigations. To maximize the gain from clinical imaging assessments, an optimized MRI/CT protocol and a structured radiological assessment and report are required.",aged;article;brain;clinical protocol;computer assisted tomography;dementia;human;methodology;nuclear magnetic resonance imaging;pathology;radiography;standard;very elderly,"Wahlund, L. O.;Westman, E.;van Westen, D.;Wallin, A.;Cavallin, L.;Larsson, E. M.",2013,,,0,
499,Contrast-enhanced MRI of white matter lesions in patients with blood-brain barrier dysfunction,"White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common in dementia. Both conditions may be a consequence of small-vessel disease, in which case the BBB damage could be suspected to be located to the WMLs. Magnetic resonance imaging (MRI) can be used to show WMLs as well as to detect BBB damage when using an intravenous contrast agent, gadolinium. We examined 10 demented patients with WMLs, including 5 cases with BBB (elevated CSF/serum albumin ratios). Results showed no significant changes in MR signal in the WMLs after contrast administration. We conclude that WMLs are not related to BBB damage to such a degree that is detectable with this method and that the elevated CSF albumin might have another origin.",Aged;Alzheimer Disease/ pathology/physiopathology;Analysis of Variance;Blood-Brain Barrier;Brain/blood supply/ pathology;Cognition Disorders/ pathology/physiopathology;Contrast Media;Female;Gadolinium DTPA;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Serum Albumin/analysis/cerebrospinal fluid,"Wahlund, L. O.;Bronge, L.",2000,Apr,,0,
500,White matter hyperintensities in dementia: does it matter?,"The aim of the study was to investigate whether the regional distribution of white matter hyperintensities (WMH) observed by magnetic resonance imaging differed between vascular dementia and patients with late onset Alzheimer's disease. Another aim was to investigate the relations between the occurrence and degree of WMH and clinical and laboratory data as well as measures of cognitive decline. White matter hyperintensities were assessed with a low field magnetic resonance imager on 23 subjects with probable Alzheimer's disease, 25 with possible Alzheimer's disease and 31 subjects with vascular dementia. The degree and regional distribution of the WMH (expressed as relative volumes) were calculated and compared in the three groups. The relation between cognitive impairment and the degree of the WMH was also studied. The regional distribution of the WMH differed between the groups with significantly more changes in the posterior part of the brain (p < .0001) as well as in the right hemisphere (p < .0005) in the vascular demented as compared to the patients with Alzheimer's disease. No significant correlations between cognitive impairment and the degree of the WMH were found in any of the groups. The total volume of the WMH as well as the regional distribution of these changes differed significantly between vascular dementia and Alzheimer's disease. White matter hyperintensities seem not to be related to the degree of global cognitive decline in dementia and whether it plays a causative role in the development of dementia symptoms needs to be more thoroughly investigated.","Aged;Alzheimer Disease/ diagnosis/psychology;Brain/ pathology;Cognition;Dementia, Vascular/ diagnosis/psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Risk Factors","Wahlund, L. O.;Basun, H.;Almkvist, O.;Andersson-Lundman, G.;Julin, P.;Saaf, J.",1994,,,0,
501,A new rating scale for age-related white matter changes applicable to MRI and CT,"Background and Purpose - MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. Methods - Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using κ statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. Results - Interrater reliability was good for MRI (κ=0.67) and moderate for CT (κ=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more Lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. Conclusions - We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.",article;basal ganglion;computer assisted tomography;diagnostic accuracy;frontal cortex;human;image processing;major clinical study;nuclear magnetic resonance imaging;patient monitoring;priority journal;cerebrovascular accident;white matter,"Wahlund, L. O.;Barkhof, F.;Fazekas, F.;Bronge, L.;Augustin, M.;Sjögren, M.;Wallin, A.;Ader, H.;Leys, D.;Pantoni, L.;Pasquier, F.;Erkinjuntti, T.;Scheltens, P.",2001,,,0,
502,Quantitative estimation of brain white matter abnormalities in elderly subjects using magnetic resonance imaging,"Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (rs = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (rs = -0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups.","Brain Diseases [diagnosis] [epidemiology];Dementia [diagnosis] [epidemiology];Intracranial Arteriosclerosis [diagnosis] [epidemiology];Magnetic Resonance Imaging;Mental Disorders [diagnosis] [epidemiology];Risk;Sweden [epidemiology];Aged[checkword];Aged, 80 and over[checkword];Humans[checkword]","Wahlund, L. O.;Andersson-Lundman, G.;Julin, P.;Nordström, M.;Viitanen, M.;Sääf, J.",1992,,,0,
503,The brain in healthy aged individuals: MR imaging,"Twenty-four healthy aged individuals with above-average intellectual function were studied with use of a low-field-strength (0.02-T) magnetic resonance (MR) imager. The group was carefully selected so as not to include persons with signs of arteriosclerotic diseases, major somatic disease, or a history of brain disease or dementia in the family. The width of the subarachnoid spaces and lateral ventricles, as well as the frequency and degree of brain white-matter lesions, were described with the use of a visual rating scale. White matter lesions were found in less than 9% of the subjects. The lateral brain ventricles were enlarged in 8% of all individuals and the cortical cerebrospinal fluid (CSF) spaces in more than 40% of all individuals. Moreover, T1 and T2 were estimated in different brain areas, and a positive correlation between T1 in the frontal white matter and age was found. A computer-assisted classification procedure was used to estimate brain tissue and CSF areas. The results of this procedure strongly correlated with the visually estimated ventricular size.","Aged;Aged, 80 and over;Aging/ pathology;Brain/ anatomy & histology;Cerebral Ventricles/anatomy & histology;Female;Humans;Image Processing, Computer-Assisted;Intelligence;Intelligence Tests;Magnetic Resonance Imaging;Male","Wahlund, L. O.;Agartz, I.;Almqvist, O.;Basun, H.;Forssell, L.;Saaf, J.;Wetterberg, L.",1990,Mar,10.1148/radiology.174.3.2305048,0,
504,[Interdisciplinary research strategies in geriatric psychiatry--studies and results in dementia and depressed patients] Interdisziplinare Forschungsstrategien in der Gerontopsychiatrie--Untersuchungen und Ergebnisse bei dementiellen und depressiven Patienten,"Eighty-one patients (mean age: 66 +/- 9 years) who had been in gerontopsychiatric in-patient care were included in the study. As well as physical, psychiatric and neurological examinations, EEG, brain CT scanning and the determination of the Ischemic Scale were performed, in order to confirm the clinical diagnosis of dementia of Alzheimer type (DAT), dementia of vascular type (DVT) or multi-infarct dementia (MID), and depression in old age, as based on the DSM III criteria. A comprehensive psychological test battery was administered, to one section of the subjects. Our results indicate that EEG and Ischemic Score can differentiate patients with DAT and DVT to a satisfactory degree, whereas CT findings and psychometric assessment were apt to confirm the overall diagnosis of dementia (DAT/DVT) and depression. Patients with dementia showed memory impairment to a greater extent than depressive patients, as could be proved by a memory test (Syndrom-Kurztest). However, a dementia screening test (Information-Memory-Concentration Test) could more accurately differentiate dementia and depression. The application of a comprehensive psychometric testing procedure did not prove to be an effective diagnostic tool in the assessment of various stages of dementia. Short dementia tests and rating scales seem to be appropriate to distinguish depression from dementia, especially in cases of mild to moderate dementia. In patients with very mild and insignificant organic brain disturbances these screening methods fall short of diagnostic validity. Beyond this, there is a current need for assessment instruments in the evaluation of alterations in personality and affectivity, such as are seen in depression.","Aged;Alzheimer Disease/diagnosis;Dementia/ diagnosis/psychology;Depressive Disorder/ diagnosis/psychology;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Patient Care Team;Psychometrics;Research","Wagner, O.;Oesterreich, K.;Hoyer, S.",1987,Jul-Aug,,0,
505,[Interdisciplinary research strategies in geriatric psychiatry--studies and results in dementia and depressed patients],"Eighty-one patients (mean age: 66 +/- 9 years) who had been in gerontopsychiatric in-patient care were included in the study. As well as physical, psychiatric and neurological examinations, EEG, brain CT scanning and the determination of the Ischemic Scale were performed, in order to confirm the clinical diagnosis of dementia of Alzheimer type (DAT), dementia of vascular type (DVT) or multi-infarct dementia (MID), and depression in old age, as based on the DSM III criteria. A comprehensive psychological test battery was administered, to one section of the subjects. Our results indicate that EEG and Ischemic Score can differentiate patients with DAT and DVT to a satisfactory degree, whereas CT findings and psychometric assessment were apt to confirm the overall diagnosis of dementia (DAT/DVT) and depression. Patients with dementia showed memory impairment to a greater extent than depressive patients, as could be proved by a memory test (Syndrom-Kurztest). However, a dementia screening test (Information-Memory-Concentration Test) could more accurately differentiate dementia and depression. The application of a comprehensive psychometric testing procedure did not prove to be an effective diagnostic tool in the assessment of various stages of dementia. Short dementia tests and rating scales seem to be appropriate to distinguish depression from dementia, especially in cases of mild to moderate dementia. In patients with very mild and insignificant organic brain disturbances these screening methods fall short of diagnostic validity. Beyond this, there is a current need for assessment instruments in the evaluation of alterations in personality and affectivity, such as are seen in depression.","Aged;Alzheimer Disease/diagnosis;Dementia/*diagnosis/psychology;Depressive Disorder/*diagnosis/psychology;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Patient Care Team;Psychometrics;Research","Wagner, O.;Oesterreich, K.;Hoyer, S.",1987,Jul-Aug,,0,
506,Longitudinal course of mild parkinsonian signs in elderly people: A population-based study in Japan,"We aimed to clarify the longitudinal course of mild parkinsonian signs (MPS) and their association with dementia and functional disability by conducting a comprehensive epidemiological study, including brain MRI, and assessments of cognition, depression, and sleep, in people aged >/=65years living in Ama-cho. We diagnosed MPS and parkinsonism (PS) using a modified Unified Parkinson's Disease Rating Scale. The phase I study was conducted between 2008 and 2010 (n=729) and the phase II between 2011 and 2013 (n=436). By phase II, 8.5% of the phase I participants without PS had developed PS. In addition to older age, a lower Mini-Mental State Examination (MMSE) score, and lower body mass index, the MPS rigidity subtype was a significant independent predictor of PS onset. By phase II, 10.1% of the participants without dementia or PS at phase I had developed dementia. Older age, lower MMSE score, and the axial dysfunction and tremor MPS subtypes were significant independent predictors of dementia development. By phase II, 38.8% of participants with MPS at phase I showed no motor symptoms. Younger age and adequate sleep were significant predictors for this reversion. Periventricular and deep white matter hyperintensity Fazekas scores increased with the evolution of parkinsonian signs. MPS is therefore critically, although sometimes reversibly, associated with PS and dementia development in elderly people.",Body mass index;Dementia;Parkinsonism;Sleep;White matter hyperintensity,"Wada-Isoe, K.;Tanaka, K.;Uemura, Y.;Nakashita, S.;Tajiri, Y.;Tagashira, S.;Yamamoto, M.;Yamawaki, M.;Kishi, M.;Nakashima, K.",2016,Mar 15,10.1016/j.jns.2016.01.016,0,
507,"Plasma fibrinogen, global cognitive function, and cerebral small vessel disease: results of a cross-sectional study in community-dwelling Japanese elderly","OBJECTIVE: Recent studies suggest that hemostatic and endothelial factors play a pivotal role in the development of cerebral small vessel disease (SVD). Although plasma fibrinogen is an essential factor in the coagulation cascade, the relationship among fibrinogen, cognitive function, and SVD has not been clarified in community-based Asian populations. Because fibrinogen levels of Asians have been reported to be lower than these of Caucasians, the impact of fibrinogen on the development of SVD or dementia in Asians may be different from that of Caucasians. METHODS: We performed a cross-sectional study using MRI to determine the relationships among fibrinogen, cognitive function, and subclinical SVD in community-based Japanese elderly. RESULTS: Subjects with raised fibrinogen levels tended to have more lacunes and higher grades of white matter lesions (WMLs). Additionally, an independent association between fibrinogen and WMLs was determined by logistic regression analyses. Subjects with high fibrinogen levels accompanied by high von Willebrand factors or thrombomodulin levels had an increased tendency for the presence of WMLs. The relationship between the mean Mini-Mental State Examination (MMSE) scores and the quartiles of fibrinogen levels was not statistically significant after controlling for age, gender, and WMLs; however, the mean MMSE scores in subjects without WML were related to the tertiles of the fibrinogen levels even after adjusting for conventional risks and high sensitivity C-reactive protein. CONCLUSION: The present study suggests that there is a close relationship between fibrinogen levels and subclinical WMLs, which are independent of conventional risk factors and inflammation, in community-based Japanese elderly.",Aged;Asian Continental Ancestry Group;Cerebrovascular Disorders/blood/*etiology/pathology/psychology;*Cognition;Cross-Sectional Studies;Female;Fibrinogen/*metabolism;Humans;Japan;Leukoencephalopathies/pathology;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Residence Characteristics;Thrombomodulin/blood;von Willebrand Factor/metabolism,"Wada, M.;Takahashi, Y.;Iseki, C.;Kawanami, T.;Daimon, M.;Kato, T.",2011,,,0,
508,"An 81-year-old man with personality change, dementia, and gait disturbance with diffuse leukoaraiosis of the cerebral white matter","We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.",aged;anamnesis;article;case report;clinical feature;dementia;disease course;gait disorder;human;kidney failure;leukoaraiosis;male;nuclear magnetic resonance imaging;personality disorder;white matter,"Wada, K.;Motoi, Y.;Komatsuzaki, Y.;Takanashi, M.;Mori, H.;Urabe, T.;Mizuno, Y.",2006,,,0,
509,Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation,"A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children.",,"Vyshka, G.;Kruja, J.",2013,,10.2147/imcrj.s51875,0,
510,Midlife CAIDE dementia risk score and dementia-related brain changes up to 30 years later on magnetic resonance imaging,"BACKGROUND: CAIDE Dementia Risk Score is a validated tool for estimating 20-year dementia risk in the general population based on a midlife risk profile. OBJECTIVE: To investigate the associations between CAIDE score and dementia-related brain changes up to 30 years later on magnetic resonance imaging (MRI). METHODS: Participants in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study were derived from random, population-based samples surveyed in 1972, 1977, 1982, or 1987. A first re-examination was conducted in 1998, and a second re-examination in 2005-2008 (total follow-up time up to 30 years). The MRI study population included 112 individuals with MRIs from the first re-examination, and a different group of 69 individuals with MRIs from the second re-examination. MRIs from 1998 were used to determine gray matter volume, and to visually rate white matter hyperintensities (WMH) of presumed vascular origin and medial temporal lobe atrophy (MTA). MRIs from 2005-2008 were used to assess cortical thickness, gray matter and WMH volume, and to visually rate MTA. CAIDE scores were calculated for participants in both re-examinations based on midlife sociodemographic and vascular factors and additionally apolipoprotein E status. RESULTS: Higher midlife CAIDE score was associated with more severe WMH 20 years later: RR (95% CI) was 1.69 (1.15-2.08); and with higher WMH volume (beta 0.27, p = 0.036) and higher MTA score (RR 1.91, 95% CI 1.16-2.34) up to 30 years later. CONCLUSION: CAIDE Dementia Risk Score in midlife was most consistently associated with WMH later in life. A relation with MTA was observed in individuals with longer follow-up time.","Adult;Aged;Aging/pathology;Apolipoproteins E/genetics;Brain/ pathology;Cardiovascular Diseases/pathology;Dementia/genetics/ pathology;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Time Factors","Vuorinen, M.;Spulber, G.;Damangir, S.;Niskanen, E.;Ngandu, T.;Soininen, H.;Kivipelto, M.;Solomon, A.",2015,,10.3233/jad-140924,0,
511,Changes in vascular risk factors from midlife to late life and white matter lesions: a 20-year follow-up study,"BACKGROUND/AIMS: This study investigated the relation of midlife blood pressure, total cholesterol, body mass index (BMI), their changes over time, apolipoprotein E, and white matter lesions (WML). METHODS: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia study were derived from random, population-based samples previously surveyed in 1972, 1977, 1982 or 1987. In 1998, 1,449 (73%) individuals aged 65-79 years were re-examined (average follow-up 21 years). A subpopulation (n = 112) was scanned with a 1.5-tesla MRI scanner in 1998, and WML were assessed from fluid-attenuated inversion recovery images using a semi-quantitative visual rating scale. RESULTS: Risk of late-life WML was related to midlife overweight (relative risk = 2.53; 95% CI = 1.70-2.89), obesity (2.94; 2.44-3.03), and hypertension (2.73; 1.81-3.08), even after adjustments for several confounding factors. Elevated BMI (>25) (2.26; 1.42-2.62) and hypertension (3.14; 1.83-3.40) from midlife to late life also increased the risk of WML. In addition, an association with WML was seen for decreasing blood pressure (hypertension at midlife but not at late life) (3.25; 2.46-3.41), even after controlling for antihypertensive treatment. Lipid-lowering drugs had a protective effect against WML (0.13; 0.02-0.59). CONCLUSIONS: These results indicate that early and sustained vascular risk factor control is associated with a lower likelihood of having more severe WML in late life.",Age Factors;Aged;Aging/psychology;Apolipoproteins E/genetics;Blood Pressure/physiology;Body Mass Index;Brain/ pathology;Cardiovascular Diseases/ epidemiology/ pathology;Cholesterol/blood;Cognition Disorders/epidemiology/psychology;Dementia/epidemiology/psychology;Female;Follow-Up Studies;Humans;Hypertension/epidemiology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Obesity/complications/epidemiology;Risk Factors,"Vuorinen, M.;Solomon, A.;Rovio, S.;Nieminen, L.;Kareholt, I.;Tuomilehto, J.;Soininen, H.;Kivipelto, M.",2011,,10.1159/000323810,0,
512,"Coronary heart disease and cortical thickness, gray matter and white matter lesion volumes on MRI","Coronary heart disease (CHD) has been linked with cognitive decline and dementia in several studies. CHD is strongly associated with blood pressure, but it is not clear how blood pressure levels or changes in blood pressure over time affect the relation between CHD and dementia-related pathology. The aim of this study was to investigate relations between CHD and cortical thickness, gray matter volume and white matter lesion (WML) volume on MRI, considering CHD duration and blood pressure levels from midlife to three decades later. The study population included 69 elderly at risk of dementia who participated in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. CAIDE participants were examined in midlife, re-examined 21 years later, and then after additionally 7 years (in total up to 30 years follow-up). MRIs from the second re-examination were used to calculate cortical thickness, gray matter and WML volume. CHD diagnoses were obtained from the Finnish Hospital Discharge Register. Linear regression analyses were adjusted for age, sex, follow-up time and scanner type, and additionally total intracranial volume in GM volume analyses. Adding diabetes, cholesterol or smoking to the models did not influence the results. CHD was associated with lower thickness in multiple regions, and lower total gray matter volume, particularly in people with longer disease duration (>10 years). Associations between CHD, cortical thickness and gray matter volume were strongest in people with CHD and hypertension in midlife, and those with CHD and declining blood pressure after midlife. No association was found between CHD and WML volumes. Based on these results, long-term CHD seems to have detrimental effects on brain gray matter tissue, and these effects are influenced by blood pressure levels and their changes over time.","Adult;Aged;Aged, 80 and over;Aging;Cerebral Cortex/*pathology;Coronary Disease/*complications;Dementia/*etiology/pathology;Female;Follow-Up Studies;Gray Matter/*pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;White Matter/*pathology","Vuorinen, M.;Damangir, S.;Niskanen, E.;Miralbell, J.;Rusanen, M.;Spulber, G.;Soininen, H.;Kivipelto, M.;Solomon, A.",2014,,10.1371/journal.pone.0109250,0,
513,Classification challenge in migrainous infarction,,alprazolam;eletriptan;fluoxetine;levothyroxine sodium;magnesium oxide;pseudoephedrine;topiramate;adult;brain stem;CADASIL;case report;disease classification;drug withdrawal;episodic migraine;female;follow up;gait disorder;hearing impairment;human;International Classification of Headache Disorders 3rd Edition;letter;migraine with aura;migrainous infarction;nausea and vomiting;neurologic disease;neurologic examination;nuclear magnetic resonance imaging;priority journal;prophylaxis;tinnitus;vertigo,"Vollbracht, S.;Robbins, M. S.;Kister, I.",2014,,,0,
514,The ZNF804A gene: Characterization of a novel neural risk mechanism for the major psychoses,"Schizophrenia and bipolar disorder share genetic risk, brain vulnerability, and clinical symptoms. The ZNF804A risk variant, rs1344706, confers susceptibility for both disorders. This study aimed to identify neural mechanisms common to both schizophrenia and bipolar disorder through this variant's potential effects on cortical thickness, white matter tract integrity, and cognitive function. Imaging, genetics, and cognitive measures were ascertained in 62 healthy adults aged between 18 and 59 years. High-resolution multimodal MRI/DTI imaging was used to measure cortical thickness and major frontotemporal and interhemispheric white matter tracts. The general linear model was used to examine the influence of the ZNF804A rs1344706 risk variant on cortical thickness, white matter tract integrity, and cognitive measures. Individuals homozygous for the risk variant (A allele) demonstrated reduced cortical gray matter thickness in the superior temporal gyrus, and in the anterior and posterior cingulate cortices compared with C-allele carriers. No effect of the risk variant on microstructural integrity of white matter tracts was found. Reduced attention control was found in risk allele homozygotes, aligning with findings in the anterior cingulate cortex. Our data provide a novel, genetically based neural risk mechanism for the major psychoses by effects of the ZNF804A risk variant on neural structures and cognitive function susceptible in both disorders. Our findings link genetic, imaging, and cognitive susceptibility relevant to both schizophrenia and bipolar disorder. © 2011 American College of Neuropsychopharmacology. All rights reserved.",,"Voineskos, A. N.;Lerch, J. P.;Felsky, D.;Tiwari, A.;Rajji, T. K.;Miranda, D.;Lobaugh, N. J.;Pollock, B. G.;Mulsant, B. H.;Kennedy, J. L.",2011,August,,0,
515,The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for Alzheimer disease,"CONTEXT: The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism may predict the risk of Alzheimer disease (AD). However, genetic association studies of the BDNF gene with AD have produced equivocal results. Imaging-genetics strategies may clarify the manner in which BDNF gene variation predicts the risk of AD via characterization of its effects on at-risk structures or neural networks susceptible in this disorder. OBJECTIVE: To determine whether the BDNF Val66Met gene variant interacts with age to predict brain and cognitive measures in healthy volunteers across the adult lifespan in an intermediate phenotype pattern related to AD by examining (1) cortical thickness, (2) fractional anisotropy of white matter tracts (ie, white matter integrity), and (3) episodic memory performance. DESIGN: A cross-sectional study using genetics, high-resolution magnetic resonance imaging, diffusion tensor imaging, and cognitive testing in healthy individuals spanning the adult lifespan. SETTING: University hospital. PARTICIPANTS: A total of 69 healthy volunteers ranging from 19 to 82 years of age. MAIN OUTCOME MEASURES: The BDNF Val66Met genotype, apolipoprotein E genotype, cortical thickness, microstructural integrity of white matter tracts, and episodic memory performance were evaluated. RESULTS: The BDNF Val66Met polymorphism interacted with age to predict (1) cortical thickness (prominently at the entorhinal cortex and temporal gyri), (2) fractional anisotropy of white matter tracts (prominently at white matter tracts connecting to the medial temporal lobe), and (3) episodic memory performance. For each of these findings, the pattern was similar: valine/valine individuals in late life were susceptible, and in early adult life, methionine allele carriers demonstrated susceptibility. CONCLUSIONS: The BDNF gene confers risk in an age-dependent manner on the brain structures and cognitive functions that are consistent with the neural circuitry vulnerable in the earliest stages of AD. Our novel findings provide convergent evidence in vivo for a BDNF genetic mechanism of susceptibility in an intermediate phenotype related to AD.","Adult;Age Factors;Aged;Aged, 80 and over;Alleles;Alzheimer Disease/diagnosis/ genetics/pathology;Apolipoprotein E4/genetics;Brain/ pathology;Brain-Derived Neurotrophic Factor/ genetics;Cerebral Cortex/pathology;Cross-Sectional Studies;Diffusion Magnetic Resonance Imaging;Female;Genetic Predisposition to Disease/ genetics;Genotype;Heterozygote Detection;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Male;Mental Recall/physiology;Middle Aged;Nerve Net/pathology;Neuropsychological Tests;Phenotype;Polymorphism, Genetic/ genetics;Polymorphism, Single Nucleotide/genetics;Risk Factors;Young Adult","Voineskos, A. N.;Lerch, J. P.;Felsky, D.;Shaikh, S.;Rajji, T. K.;Miranda, D.;Lobaugh, N. J.;Mulsant, B. H.;Pollock, B. G.;Kennedy, J. L.",2011,Feb,10.1001/archgenpsychiatry.2010.194,0,
516,Neuroimaging and correlates of cognitive function among patients with heart failure,"Background/Aims: We purposed to investigate the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure (HF). Methods: In 58 patients with HF neuropsychological assessment was performed including tests of mental speed, executive functions, memory, language and visuospatial functions. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated on MRI of the brain. Correlations between MRI findings and the cognitive measures were calculated. Results: MTA correlated with memory (r = -0.353, p < 0.01), with executive functions (r = -0.383, p < 0.01) and the Mini Mental State Examination (r = -0.343, p < 0.05). Total WMH and deep WMH were found to correlate with depression and anxiety scores, but not with cognitive measures. Age, estimated premorbid intelligence and MTA were independent predictors of diminished cognitive performance. Conclusions: In HF patients, MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH was related to depression and anxiety. Copyright © 2007 S. Karger AG.",,"Vogels, R. L. C.;Oosterman, J. M.;Van Harten, B.;Gouw, A. A.;Schroeder-Tanka, J. M.;Scheltens, P.;Van Der Flier, W. M.;Weinstein, H. C.",2007,November,,0,
517,Cerebral Microbleed Causing an Acute Stroke-like Episode in a CADASIL Patient,,Notch3 receptor;adult;article;brain hemorrhage;brain ischemia;brain tissue;CADASIL;case report;cerebrovascular accident;computed tomographic angiography;diplopia;exon;follow up;headache;human;incidental finding;male;middle aged;migraine with aura;missense mutation;nausea;neurologic disease;nuclear magnetic resonance imaging;photophobia;priority journal;risk factor;tissue necrosis;vertical strabismus;vertigo,"Vitali, P.;Boghen, D.;Daneault, N.;Guillon-Létourneau, L.;Poppe, A. Y.",2014,,,0,
518,Tissue microstructural changes are independently associated with cognitive impairment in cerebral amyloid angiopathy,"BACKGROUND AND PURPOSE-Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment. METHODS-Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0±22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding. RESULTS-Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4×10(-4) versus 11.7×10(-4) mm/s; P≤0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1×10(-4) mm/s increase≤2.45, 95% CI 1.11 to 5.40, P≤0.04). CONCLUSIONS-Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage. © 2008 American Heart Association, Inc.",,"Viswanathan, A.;Patel, P.;Rahman, R.;Nandigam, R. N. K.;Kinnecom, C.;Bracoud, L.;Rosand, J.;Chabriat, H.;Greenberg, S. M.;Smith, E. E.",2008,1,,0,
519,Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: A two-centre cohort study,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T 1-weighted, FLAIR and T2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin A1c (HbA1c) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease. © The Author (2006). Published by Oxford University Press. All rights reserved.",glucose;hemoglobin A1c;adult;aged;article;basal ganglion;blood pressure;blood pressure regulation;brain hemorrhage;brain infarction;brain infarction size;brain stem;CADASIL;cognitive defect;cohort analysis;controlled study;disability;disease association;disease course;disease marker;disease predisposition;disease severity;female;gene;gene mutation;human;hypertension;major clinical study;male;NOTCH3 gene;nuclear magnetic resonance imaging;priority journal;qualitative analysis;Rankin scale;rating scale;risk factor;standardization;systolic blood pressure;white matter,"Viswanathan, A.;Guichard, J. P.;Gschwendtner, A.;Buffon, F.;Cumurcuic, R.;Boutron, C.;Vicaut, E.;Holtmannspötter, M.;Pachai, C.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2006,,,0,
520,Lacunar lesions are independently associated with disability and cognitive impairment in CADASIL,"OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The disease is characterized by T2-hyperintense lesions (subcortical white matter lesions), T1-hypointense lesions (lacunar lesions), and T2*-weighted gradient-echo (GE) lesions (cerebral microhemorrhages [CMs]) visualized on clinical MRI sequences and is considered as a model of ""pure"" subcortical ischemic vascular dementia. Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL, the clinical importance of lacunar lesions remains unknown. Our purpose was to examine the influence of the visible MRI markers in the disease, including the load of lacunar lesions on cognitive impairment and disability in CADASIL. METHODS: We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospective cohort study. Degree of disability was assessed by modified Rankin scale and Barthel index. Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination. T1-weighted, fluid-attenuated inversion recovery, and GE images were obtained on a 1.5-T MRI. Volume and location of lacunar lesions, white matter hyperintensities (WMHs), and CMs were assessed. RESULTS: There was a significant independent association between age, volume of lacunar lesions, and global cognitive function scales when analyzed in a multivariable model. In contrast, WMHs and CMs had no independent influence on cognitive function. Disability in this cohort was associated with volume of lacunar lesions, CMs, systolic blood pressure, and age but not with WMHs. CONCLUSIONS: Among the lesions observed on conventional MRI in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the overall lacunar lesion burden seems to have the most important impact on cognitive function and disability. These findings suggest that preventive strategies to decrease the risk of lacunar lesions as observed on MRI may reduce disease-related impairment in CADASIL. These results suggest that lacunar lesions may also play a key role in disability and cognitive impairment in more common forms of small-vessel disease.","Adult;Age Distribution;Aged;Aging/pathology;Brain Infarction/ epidemiology/ pathology/psychology;CADASIL/ epidemiology/ pathology/psychology;Cerebral Arteries/pathology/physiopathology;Cerebral Cortex/blood supply/pathology/physiopathology;Cognition Disorders/ epidemiology/ pathology/psychology;Cohort Studies;Comorbidity;Disability Evaluation;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Predictive Value of Tests;Prognosis;Prospective Studies","Viswanathan, A.;Gschwendtner, A.;Guichard, J. P.;Buffon, F.;Cumurciuc, R.;O'Sullivan, M.;Holtmannspotter, M.;Pachai, C.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2007,Jul 10,10.1212/01.wnl.0000265221.05610.70,0,
521,Cortical neuronal apoptosis in CADASIL,"BACKGROUND AND PURPOSE - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the NOTCH3 gene and is a model of pure vascular dementia. Cortical atrophy has been reported to be associated with cognitive decline in the disease, although the underlying mechanism is unknown. We postulated that apoptosis may be involved in this process. METHODS - We report the clinical history, magnetic resonance imaging findings, and pathologic examinations of 4 patients (2 of whom were demented) who died from complications of the disease. Apoptosis was evaluated in brain tissue using antibodies against activated caspase3 and in situ end labeling assays for DNA fragmentation. RESULTS - Widespread neuronal apoptosis in the cerebral cortex (predominantly in layers 3 and 5) was observed in all patients. This was not seen in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was more extensive in the presence of larger load of subcortical ischemic lesions and smaller brain volumes. CONCLUSIONS - Neuronal apoptosis may be involved in cortical atrophy in CADASIL and appears related to the burden of subcortical ischemic lesions. These findings may have important implications in other small vessel diseases and may provide a potential target for future therapeutic interventions. © 2006 American Heart Association, Inc.",,"Viswanathan, A.;Gray, F.;Bousser, M. G.;Baudrimont, M.;Chabriat, H.",2006,November,,0,
522,Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL,"CADASIL is an arteriopathy caused by mutations of the Notch3 gene. White matter hyperintensities (WMH), lacunar lesions (LL), cerebral microhemorrhages (CM), brain atrophy and tissue microstructural changes are detected on MRI. Using an integrated multi-modal approach, we examined the relative impact of lesion burden and location of these MRI markers on cognitive impairment and disability. Multi-modal imaging was performed on 147 patients from a two-center cohort study. Volume of LL, WMH and number of CM was determined. Whole brain mean apparent diffusion coefficient (mean-ADC) and brain parenchymal fraction (BPF) were measured. In multivariate models accounting for lesion burden and location, volume of LL, mean-ADC, and BPF each had an independent influence on global cognitive function and disability. BPF explained the largest portion of the variation in cognitive and disability scores (35-38%). Brain atrophy has the strongest independent influence on clinical impairment in CADASIL when all MRI markers in the disease are considered together. The results suggest that the clinical impact of cerebral tissue loss plays a principal role in this genetic model of subcortical ischemic vascular dementia.","Brain/ pathology;CADASIL/ pathology;Female;France;Germany;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Multivariate Analysis;Reproducibility of Results;Sensitivity and Specificity","Viswanathan, A.;Godin, O.;Jouvent, E.;O'Sullivan, M.;Gschwendtner, A.;Peters, N.;Duering, M.;Guichard, J. P.;Holtmannspotter, M.;Dufouil, C.;Pachai, C.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2010,Sep,10.1016/j.neurobiolaging.2008.09.001,0,
523,Cerebral microhemorrhage,"Background and Purpose - With the advent of modern MRI imaging techniques, cerebral microhemorrhages have been increasingly recognized on gradient-echo (GE) or T2*-weighted MRI sequences in different populations. However, in clinical practice, their diagnostic value, associated risk, and prognostic significance are often unclear. This review summarizes the pathophysiology, differential diagnosis, epidemiology, and clinical significance of cerebral microhemorrhages. Summary of Review - Focal areas of signal loss on GE MRI imaging pathologically represent focal hemosiderin deposition associated with previous hemorrhagic events. Cerebral microhemorrhages have been noted in healthy elderly, ischemic cerebrovascular disease, intracerebral hemorrhage (ICH), cerebral amyloid angiopathy (CAA), and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Microhemorrhages have been associated with older age, hypertension, smoking, white matter disease, lacunar infarcts, previous ischemic stroke, or ICH. In CAA, microhemorrhages predict both the risk of recurrent lobar ICH and future clinical decline. In patients with ischemic cerebrovascular disease, microhemorrhage number and location may be associated with executive dysfunction and may predict the occurrence of ICH and lacunar infarction. Conclusions - When cerebral microhemorrhages are diagnosed on MRI, conclusions regarding their significance and associated risks should be made based on the population examined. Further studies to characterize the associated risks of cerebral microhemorrhages in different stroke populations are needed to use this new imaging marker in therapeutic decisions. © 2006 American Heart Association, Inc.",,"Viswanathan, A.;Chabriat, H.",2006,February,,0,
524,The first report of CADASIL in Peru: Olfactory dysfunction on initial presentation,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare, heritable, small vessel vascular disease caused by mutations in the Notch3 gene that is characterized by migraines, subcortical vascular events, cognitive decline, and mood disturbances. However, many CADASIL cases present with unusual symptoms such as status epilepticus, a movement disorder, or sensory dysfunction. This study describes the clinical, genetic, and radiologic characteristics of a Peruvian family with CADASIL in which multiple family members presented with severe olfactory deficits. Seven members of the family have symptoms suggestive of CADASIL, with genetic testing revealing R133C mutations in the two patients who underwent genetic testing. Cognitive testing and olfactory identification testing (Smell Identification Test) were performed in three CADASIL patients revealing total anosmia in two tested patients and severe hyposmia in the other. Olfactory dysfunction has been associated with various neurologic and psychiatric conditions, though few studies have linked it with neurovascular disorders such as CADASIL. This first reported case of CADASIL in Peru emphasizes that symptomatic olfactory dysfunction may be an unusual presentation of CADASIL and that olfactory dysfunction is important to evaluate in CADASIL patients.",adult;aged;amnesia;anosmia;apraxia;article;Babinski reflex;brain hemorrhage;brain ischemia;CADASIL;case report;cerebrovascular accident;chronicity;cognitive function test;corpus callosum;depression;dysarthria;dyslipidemia;family;female;gene mutation;genetic screening;hemiparesis;hospitalization;human;hypesthesia;hyposmia;leukoencephalopathy;male;middle aged;nausea;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;odor recognition test;paresthesia;parietal cortex;Peru;Peruvian;photophobia;priority journal;sleep disorder;smelling disorder;subcortex;visual acuity;weakness,"Vishnevetsky, A.;Inca-Martinez, M.;Milla-Neyra, K.;Barrientos-Iman, D. M.;Cornejo-Herrera, I.;Cosentino, C.;Cornejo-Olivas, M.",2016,,10.1016/j.ensci.2016.09.001,0,
525,Handgrip Strength Predicts Longitudinal Changes in Clock Drawing Test Performance. An Observational Study in a Sample of Older Non-Demented Adults,"OBJECTIVE: Impairment of physical performance might identify older people at higher risk of dementia over time. The present study evaluated handgrip strength as independent predictor of cognitive decline. DESIGN: Observational, prospective. Follow-up duration: 11.2 +/- 0.8 months. SETTING AND PARTICIPANTS: Geriatric outpatients center. 104 consecutive stroke- and dementia-free older adults (44% men, ages 80.2 +/- 5.4 years). METHODS: The Clinical Dementia Rating scale and the Clock Drawing Test (CDT) were administered. Handgrip strength was assessed using a Jamar hand dynamometer. Brain magnetic resonance imaging studies at 1.5 T were performed. White matter damage was expressed as severity of white matter hyperintensities (WMHs). Longitudinal changes in cognitive function were expressed as 1-year decline in CDT performance. RESULTS: A robust association was observed between baseline handgrip strength and 1-year cognitive decline after multiple adjustment. Of note, the strength of such association was only minimally attenuated after adjusting for deep WMHs extent (beta coefficient for handgrip strength = 0.183, SE= 0.038, p= 0.007, R2= 0.58). CONCLUSIONS: Handgrip strength predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older adults. Future studies are needed to elucidate the causal mechanisms linking limitations in physical function with dementia risk.","Aged;Aged, 80 and over;Cognition;Cognitive Dysfunction/etiology;Dementia;Female;Hand Strength;Humans;Magnetic Resonance Imaging;Male;Prospective Studies;Stroke;Task Performance and Analysis;White Matter;Physical performance;cognitive decline;handgrip;present work.","Viscogliosi, G.;Di Bernardo, M. G.;Ettorre, E.;Chiriac, I. M.",2017,,,0,526
526,Handgrip strength predicts longitudinal changes in clock drawing test performance. An observational study in a sample of older non-demented adults,"Objective: Impairment of physical performance might identify older people at higher risk of dementia over time. The present study evaluated handgrip strength as independent predictor of cognitive decline. Design: Observational, prospective. Follow-up duration: 11.2 ± 0.8 months. Setting and participants: Geriatric outpatients center. 104 consecutive stroke- and dementia-free older adults (44% men, ages 80.2±5.4 years). Methods: The Clinical Dementia Rating scale and the Clock Drawing Test (CDT) were administered. Handgrip strength was assessed using a Jamar hand dynamometer. Brain magnetic resonance imaging studies at 1.5 T were performed. White matter damage was expressed as severity of white matter hyperintensities (WMHs). Longitudinal changes in cognitive function were expressed as 1-year decline in CDT performance. Results: A robust association was observed between baseline handgrip strength and 1-year cognitive decline after multiple adjustment. Of note, the strength of such association was only minimally attenuated after adjusting for deep WMHs extent (β coefficient for handgrip strength = 0.183, SE= 0.038, p= 0.007, R2= 0.58). Conclusions: Handgrip strength predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older adults. Future studies are needed to elucidate the causal mechanisms linking limitations in physical function with dementia risk..",adult;aged;cerebrovascular accident;Clinical Dementia Rating;clock drawing test;cognitive defect;dynamometer;female;follow up;genetic polymorphism;grip strength;human;human tissue;major clinical study;male;nuclear magnetic resonance imaging;observational study;outpatient;physical performance;very elderly;white matter,"Viscogliosi, G.;Di Bernardo, M. G.;Ettorre, E.;Chiriac, I. M.",2016,,10.1007/s12603-016-0816-9,0,
527,Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions,"Aims Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain-specific cognitive tests in older non-demented subjects independently of its individual components, WMH severity and other variables. Methods MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III definition. Brain magnetic resonance studies (1.5T) were performed. Deep and periventricular WMH were graded using the Fazekas scale. Subjects underwent the Mini-Mental State Examination, the Babcock Short Story Recall test and the Clock-Drawing Test (CDT). Results Eighty community-dwellers aged 67-91 years were studied. Subjects with MetS (n = 35) had more severe WMH, and poorer performances on the CDT (P = 0.003) and the Babcock Short Story Recall test (P = 0.027). After multiple adjustment, MetS was inversely associated with CDT scores (B = -1.285; 95% confidence interval = -1.996 - 0.575; P = 0.001) but not with episodic memory. Results were not affected by WMH severity. Interestingly, none of the individual components of MetS predicted poorer cognitive performances. Conclusions Impairment in executive functions assessed by CDT may represent an early and specific sign of cognitive decline in older individuals with MetS. Future longitudinal studies are needed to better establish the predictive role of MetS on dementia and to demonstrate the possibility of dementia prevention by targeting MetS.",antidepressant agent;antihypertensive agent;antilipemic agent;antithrombocytic agent;aged;article;Babcock Short Story Recall test;clinical article;clock drawing test;cognition;cognitive defect;cognitive function test;community living;controlled study;depression;disease association;disease severity;episodic memory;executive dysfunction;Fazekas scale;female;human;hypertension;male;metabolic syndrome X;Mini Mental State Examination;nuclear magnetic resonance imaging;rating scale;very elderly;white matter hyperintensity;white matter lesion,"Viscogliosi, G.;Chiriac, I. M.;Andreozzi, P.;Ettorre, E.",2015,,,0,
528,The nature of episodic memory deficits in MCI with and without vascular burden,"This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic memory processes were measured with free recall and temporal contextual memory tasks requiring self-initiated retrieval. Nonstrategic memory retrieval processes were appraised with a five-choice recognition procedure. Results showed that MCI participants with high vascular burden displayed impairment of strategic memory processes, whereas MCI participants with no vascular burden showed impairment of both strategic and nonstrategic memory processes. A similar pattern was found whether vascular burden was measured using a clinical index of vascular risk profile or whether it was measured neuroradiologically by assessing the extent and severity of subcortical WML. However, the effect of WML on memory differed as function of level of education, used here as a proxy for cognitive reserve. Among participants with MCI, those who had higher education and no WML were the least memory impaired. The study also examined memory as a function of whether patients later progressed to dementia after a three-year follow-up. When examining progressors' performance, strategic and nonstrategic processes were both impaired in progressors with no concomitant vascular conditions, whereas progressors with a high vascular burden showed less impairment of nonstrategic than strategic processes. Overall, results indicate that the presence of vascular burden in MCI is associated with selective impairment of strategic memory processes.","Aged;Cognitive Reserve/physiology;Dementia, Vascular/classification/*psychology;Disease Progression;Educational Status;Executive Function/physiology;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory/physiology;Memory Disorders/classification/*psychology;*Memory, Episodic;Mental Recall/physiology;Mild Cognitive Impairment/classification/*psychology;Neuropsychological Tests;Psychomotor Performance/physiology;Recognition (Psychology)/physiology;Risk Assessment;Socioeconomic Factors;Vascular Diseases/complications/psychology","Villeneuve, S.;Massoud, F.;Bocti, C.;Gauthier, S.;Belleville, S.",2011,Sep,10.1016/j.neuropsychologia.2011.07.001,0,
529,Imaging Vascular Disease and Amyloid in the Aging Brain: Implications for Treatment,"Vascular risk factors (e.g. hypertension, dyslipidemia and diabetes) are well known risk factors for Alzheimer' disease. These vascular risk factors lead to vascular brain injuries, which also increase the likelihood of dementia. The advent of amyloid PET imaging has helped establish that vascular risk factors also lead to Alzheimer's disease via pathways that are independent from vascular brain injuries, at least, when vascular brain injuries are measured as white matter lesions and infarcts. While vascular brain injuries (white matter lesions and infarcts) do not seem to influence amyloid pathology, some evidence from amyloid imaging suggests that increased vascular risk is related to increased amyloid burden. Furthermore, while vascular brain injuries and amyloid have an additive and independent impact on brain integrity, vascular risk factors might potentiate the impact of amyloid on cortical thickness on brain regions vulnerable to Alzheimer's disease. New research should further explore and confirm, or refute, possible interactions between amyloid and vascular risk factors on brain integrity and cognition. Neuroimaging tools used to assess vascular brain integrity should also be expanded. Measuring cortical blood flow or damage to the capillary system might, for instance, give insight about how vascular risk factors can be associated to amyloid burden and impact. These findings also stress the need for monitoring vascular risk factors in midlife as a strategy for Alzheimer's disease prevention.",,"Villeneuve, S.;Jagust, W. J.",2015,Mar,10.14283/jpad.2015.47,0,
530,In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease,"PURPOSE: Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate (18)F-THK523 as a potential tau imaging tracer. METHODS: Ten healthy elderly controls, three semantic dementia (SD) and ten AD patients underwent neuropsychological examination, MRI as well as (18)F-THK523 and (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET) scans. Composite memory and non-memory scores, global and hippocampal brain volume, and partial volume-corrected tissue ratios for (18)F-THK523 and (11)C-PIB were estimated for all participants. Correlational analyses were performed between global and regional (18)F-THK523, (11)C-PIB, cognition and brain volumetrics. RESULTS: (18)F-THK523 presented with fast reversible kinetics. Significantly higher (18)F-THK523 retention was observed in the temporal, parietal, orbitofrontal and hippocampi of AD patients when compared to healthy controls and SD patients. White matter retention was significantly higher than grey matter retention in all participants. The pattern of cortical (18)F-THK523 retention did not correlate with Abeta distribution as assessed by (11)C-PIB and followed the known distribution of tau in the AD brain, being higher in temporal and parietal areas than in the frontal region. Unlike (11)C-PIB, hippocampal (18)F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy. CONCLUSION: (18)F-THK523 does not bind to Abeta in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain. Significantly higher cortical (18)F-THK523 retention in AD patients as well as the association of hippocampal (18)F-THK523 retention with cognitive parameters and hippocampal volume suggests (18)F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high (18)F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.","Aged;Aged, 80 and over;Alzheimer Disease/ radionuclide imaging;Amyloid beta-Peptides/metabolism;Aniline Compounds/pharmacokinetics;Brain/radionuclide imaging;Case-Control Studies;Female;Frontotemporal Dementia/radionuclide imaging;Humans;Male;Middle Aged;Positron-Emission Tomography;Protein Binding;Quinolines/pharmacokinetics;Radiopharmaceuticals/pharmacokinetics;Thiazoles/pharmacokinetics;Tissue Distribution;tau Proteins/ metabolism","Villemagne, V. L.;Furumoto, S.;Fodero-Tavoletti, M. T.;Mulligan, R. S.;Hodges, J.;Harada, R.;Yates, P.;Piguet, O.;Pejoska, S.;Dore, V.;Yanai, K.;Masters, C. L.;Kudo, Y.;Rowe, C. C.;Okamura, N.",2014,May,10.1007/s00259-013-2681-7,0,
531,Mirrored-self misidentification in a patient without dementia: Evidence for right hemispheric and bifrontal damage mirrored-self misidentification in a patient without dementia,"Mirrored-self misidentification, often referred as the 'mirror sign', is a delusion characterized by the inability to recognize one's own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimer's disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition. © 2010 Psychology Press.",,"Villarejo, A.;Martin, V. P.;Moreno-Ramos, T.;Camacho-Salas, A.;Porta-Etessam, J.;Bermejo-Pareja, F.",2011,June,,0,
532,Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree,"The cognitive and behavioral effects and the safety of oxiracetam therapy during a placebo-controlled trial and the relevant follow-up up to 1 year in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) of mild to moderate degree were studied. Sixty male and female outpatients participated in the double-blind, placebo-controlled, parallel-group, randomized trial, comparing the effects of oxiracetam 800 mg b.i.d. and placebo during 90 days of treatment. At the end of therapy, statistical analysis evidenced significant improvements in the group receiving oxiracetam in respect to the placebo group on Mini Mental State Examination, Auditory Continuous Performance Test, Rey's 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series and Instrumental Activities of Daily Living. Afterwards, 29 of the 30 patients who received oxiracetam, participated in the open follow-up study, receiving 800 mg b.i.d. oxiracetam for a total standard period of 1 year. Statistical improvements in comparison to baseline were again found on the same tests of the first 90 days (except for Rey's 15 Words Test) and on the Memory item of the Inventory of Psychic and Somatic Complaints Elderly. During the late phase of the follow-up, statistically significant worsenings in comparison to baseline were observed on Digit Span Backward, Gibson's Spiral and some non-memory items of IPSC-E. Neither severe adverse events were observed during the whole study, nor changes in routine laboratory examinations. In conclusion, in the present population of patients with mild to moderate degree dementia, the safety of 1,600 mg/day of oxiracetam also up to 1 year of treatment was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)","Alzheimer Disease [drug therapy];Cognition Disorders [drug therapy] [physiopathology];Dementia, Multi-Infarct [drug therapy];Double-Blind Method;Follow-Up Studies;Memory Disorders [drug therapy];Neuropsychological Tests;Placebos;Psychiatric Status Rating Scales;Pyrrolidines [administration & dosage] [therapeutic use];Tomography, X-Ray Computed;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia","Villardita, C.;Grioli, S.;Lomeo, C.;Cattaneo, C.;Parini, J.",1992,,118805,0,
533,Sequential relationships between grey matter and white matter atrophy and brain metabolic abnormalities in early Alzheimer's disease,"Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 x 10(-)(3)) and uncinate fasciculus (r = 0.75; P = 7 x 10(-)(4)) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 x 10(-)(3)); and anterior (r = 0.74; P = 1 x 10(-)(3)) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 x 10(-)(3)). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/ pathology;Atrophy;Brain/ metabolism/ pathology;Cerebral Cortex/metabolism/ pathology;Female;Follow-Up Studies;Hippocampus/metabolism/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/metabolism/ pathology;Time Factors","Villain, N.;Fouquet, M.;Baron, J. C.;Mezenge, F.;Landeau, B.;de La Sayette, V.;Viader, F.;Eustache, F.;Desgranges, B.;Chetelat, G.",2010,Nov,10.1093/brain/awq203,0,
534,"Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer's disease","In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/ pathology/radionuclide imaging;Atrophy;Brain Mapping;Case-Control Studies;Female;Fluorodeoxyglucose F18/metabolism;Hippocampus/ pathology/radionuclide imaging;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuroglia/ pathology/radionuclide imaging;Neurons/ pathology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography/methods;Statistics as Topic","Villain, N.;Desgranges, B.;Viader, F.;de la Sayette, V.;Mezenge, F.;Landeau, B.;Baron, J. C.;Eustache, F.;Chetelat, G.",2008,Jun 11,10.1523/jneurosci.1392-08.2008,0,
535,Neuroimaging in Alzheimer's disease: A synthesis and a contribution to the understanding of physiopathological mechanisms,"Alzheimer's disease has become a major public health issue for occidental societies. Since animal models of Alzheimer's disease currently fail to perfectly mimic pathophysiological mechanisms or the manifestations of the disease, in vivo neuroimaging has a key role in better understanding the pathophysiology of Alzheimer's disease. The diversity of anatomical and functional neuroimaging techniques - anatomical (T1-MRI), functional (fMRI) and diffusion tensor imaging (DTI) via magnetic resonance imaging (MRI) as well as positon emission tomography coupled to fluorodeoxyglucose ((-18)FDG- PET) - offers a large possibility of investigation of brain alterations in Alzheimer's disease. These techniques have thus provided morphological and functional brain alterations mapping of Alzheimer's disease: on one hand grey matter atrophy first concerns the medial temporal lobe before extending to the temporal neocortex and then other neocortical areas; on the other hand, metabolic alterations are first located within the posterior cingulate cortex and then reach the temporo-parietal area as well as the prefrontal cortex, especially in its medial part. Assessments of white matter alterations with DTI have highlighted a variety of tract alterations including the cingulum bundle, a white matter tract connecting the medial temporal lobe to the posterior cingulate cortex. Finally fMRI activation studies have evidenced compensatory mechanisms through hyperactivations in Alzheimer's disease patients. Altogether these results have led to the hypothesis of two major pathophysiological mechanisms in Alzheimer's disease: on one hand compensatory mechanisms in regions where atrophy exceeds metabolic alterations, on the other disconnection between medial temporal lobe and posterior cingulate cortex through the cingulum bundle, accounting for higher metabolic than structural alterations in the posterior cingulate cortex. Our work has extensively contributed to this disconnection hypothesis thanks to the use of cross-sectional and longitudinal multi-modal neuroimaging approaches. It has underlined the relevance of distant over local mechanisms in the pathophysiology of Alzheimer's disease and offers new perspectives to the exploration of the neural bases of cognitive impairments in this disorder. © 2010 Société de Biologie.",,"Villain, N.;Chételat, G.;Desgranges, B.;Eustache, F.",2010,2010,,0,
536,N-glycome Profile Levels Relate to Silent Brain Infarcts in a Cohort of Hypertensives,"BACKGROUND: Silent brain infarcts (SBIs) are highly prevalent in the aged population and relate to the occurrence of further stroke and dementia. Serum N-glycome levels have been previously associated with aging and they might be related as well to the presence of SBIs and age-related white matter hyperintensities. METHODS AND RESULTS: We determined the serum N-glycome profile in a cohort study comprising 972 subjects and evaluated the relationship between N-glycome levels and the presence and number of SBIs and with age-related white matter hyperintensities grades, assessed by brain magnetic resonance imaging. Decreasing concentrations of bigalacto core-alpha-1,6-fucosylated biantennary glycan and increasing concentrations of branching alpha-1,3-fucosylated triantennary glycan remained as independent predictors of SBIs (odds ratio 0.4, 95% CI 0.3-0.7 and odds ratio 1.8, 95% CI 1-3.2, respectively), after controlling for the presence of age and classic vascular risk factors. A similar pattern was found to be related to an increasing number of SBIs and white matter hyperintensities grade. CONCLUSIONS: N-glycome levels might be potentially useful as biomarkers for the presence of silent cerebrovascular disease.",,"Vilar-Bergua, A.;Riba-Llena, I.;Vanhooren, V.;Dewaele, S.;Libert, C.;Penalba, A.;Montaner, J.;Delgado, P.",2015,Nov,10.1161/jaha.115.002669,0,
537,N-terminal pro-brain natriuretic peptide and subclinical brain small vessel disease,"OBJECTIVE: To study the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with several brain MRI markers of brain vascular disease in a sample of participants free of stroke and dementia. METHODS: NT-proBNP plasma level was determined by means of a sandwich immunoassay method in a cohort study comprising 278 hypertensive patients. The presence of silent brain infarcts, brain microbleeds, enlarged perivascular spaces, and white matter hyperintensity volumes was assessed by brain MRI. We performed univariate and multivariate analyses to determine whether NT-proBNP was independently associated with these imaging markers, individually or combined. RESULTS: Median age was 63 years, and 41.4% were women. NT-proBNP remained independently associated with silent brain infarcts (odds ratio [OR] per 1-SD increase in NT-proBNP 2.11, 95% confidence interval [CI] 1.44-3.10), brain microbleeds (OR 1.79, 95% CI 1.15-2.78), basal ganglia enlarged perivascular spaces (OR 1.55, 95% CI 1.12-2.15), and white matter hyperintensity volumes (beta 1.60, 95% CI 0.47-2.74), even after controlling for vascular risk factors, cardiovascular risk, atrial fibrillation, previous heart disease, duration of hypertension, and preventive treatments. A score combining several imaging markers was also related to NT-proBNP levels (common OR per 1-SD increase 1.74, 95% CI 1.21-2.50). CONCLUSIONS: NT-proBNP is independently associated with silent cerebrovascular lesions and could be a surrogate marker of vascular brain damage in hypertension.",,"Vilar-Bergua, A.;Riba-Llena, I.;Penalba, A.;Cruz, L. M.;Jimenez-Balado, J.;Montaner, J.;Delgado, P.",2016,Dec 13,,0,
538,CADASIL: A short review of the literature and a description of the first family from Greece,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease clinically characterized by migraine, subcortical ischemic events, dementia and mood disorders. We present a short review of the literature on the clinical presentation of patients with CADASIL and provide recommendations for the detection and diagnosis of similar cases. We also describe the clinical, radiological and genetic findings of two Greek patients with CADASIL, members of the same family.",acetylsalicylic acid;benzodiazepine;serotonin uptake inhibitor;adult;brain ischemia;CADASIL;case report;clinical feature;dementia;familial disease;female;genetic analysis;genetic disorder;Greece;human;literature;male;migraine;mood disorder;nuclear magnetic resonance imaging;radiodiagnosis;short survey;aspirin,"Vikelis, M.;Xifaras, M.;Mitsikostas, D. D.",2006,,,0,
539,A novel CADASIL-causing mutation in a stroke patient,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an uncommon autosomal dominant genetic disease due to mutations in the Notch3 gene on chromosome 19. The major clinical characteristics of CADASIL are migraine, recurrent ischaemic strokes and dementia. Case report: We describe the case of a 58-year-old man who presented with a minor stroke that occurred in the absence of significant vascular risk factors. His family history included stroke, dementia and early death. An MRI brain scan demonstrated hyperintensities in the white matter on FLAIR images with prominent involvement of the area of the external capsule bilaterally. Based on the family history and the MRI findings, CADASIL was suspected. Mutational analysis of the Notch3 gene disclosed a novel mutation substituting cysteine for glycine at codon 251 in exon 5, confirming the diagnosis of CADASIL. Conclusion: This case suggests that CADASIL should be suspected in patients with stroke that arises in the absence of known vascular risk factors, especially if there are typical MRI findings. A strong family history of stroke and dementia are also supportive.",,"Vikelis, M.;Papatriantafyllou, J.;Karageorgiou, C. E.",2007,2,,0,
540,Fractional anisotropy shows differential reduction in frontal-subcortical fiber bundles - A longitudinal MRI study of 76 middle-aged and older adults,"Motivated by the frontal- and white matter (WM) retrogenesis hypotheses and the as sumptions that fronto-striatal circuits are especially vulnerable in normal aging, the goal of the present study was to identify fiber bundles connecting subcortical nuclei and frontal areas and obtain site-specific information about age related fractional anisotropy (FA) changes. Multimodal magnetic resonance image acquisitions (3D T1-weighted and diffusion weighted imaging (DWI)) were obtained from healthy older adults (N=76, range 49-80 years at inclusion) at two time points, three years apart. A subset of the partic ipants (N=24) was included at a third time-point. In addition to the frontal-subcortical fibers, the anterior callosal fiber (ACF) and the corticospinal tract (CST) was investigated by its mean FA together with tract parameterization analysis. Our results demonstrated fronto-striatal structural connectivity decline (reduced FA) in normal aging with substan tial inter-individual differences. The tract parameterization analysis showed that the along tract FA profiles were characterized by piece-wise differential changes along their extension rather than being uniformly affected. To the best of our knowledge, this is the first longitudinal study detecting age-related changes in frontal-subcortical WM connections in normal aging.",,"Vik, A.;Hodneland, E.;Haász, J.;Ystad, M.;Lundervold, A. J.;Lundervold, A.",2015,,,0,
541,"LAMA2 stop-codon mutation: Merosin-deficient congenital muscular dystrophy with occipital polymicrogyria, epilepsy and psychomotor regression","Merosin-deficient congenital muscular dystrophy (MD) type 1A (MDC1A) is one of the most frequent forms of CMD in Western countries. The classical form, characterized by a total lack of laminin α2 chain expression, usually shows severe clinical features; cases with complete laminin α2 deficiency and mild phenotype have also been reported, although the mechanisms underlying the lack of genotype-phenotype correlation have not been elucidated. Epilepsy and focal cortical dysplasia-in addition to the classical diffuse white matter abnormalities-have been described in some of these patients associated with cognitive deterioration. We report on a patient with total laminin α2 deficiency due to a homozygous stop-codon mutation in the LAMA2 gene, with mild evolution. When 6.9 years old, she developed focal occipital seizures and absence-like status when awake, with probable relation to an extensive bilateral occipital micropolygyria. Soon afterwards she lost ambulation and developed cognitive deterioration. Our case confirms that the clinical spectrum of MDC1A is more heterogeneous than previously thought. © 2008 European Paediatric Neurology Society.",4 aminobutyric acid;carbamazepine;DNA;gamma vinil;laminin alpha2;merosin;topiramate;unclassified drug;valproic acid;article;brain;case report;child;defense mechanism;DNA determination;electroencephalogram;electromyogram;epilepsy;female;focal epilepsy;gene mutation;homozygote;human;human tissue;mental deterioration;microgyria;mobilization;molecular evolution;motor performance;muscular dystrophy;nuclear magnetic resonance imaging;occipital polymicrogyria;priority journal;protein deficiency;psychomotor performance;stop codon;wakefulness,"Vigliano, P.;Dassi, P.;Blasi, C. D.;Mora, M.;Jarre, L.",2009,,,0,
542,Dementia following treatment of brain tumors with radiotherapy administered alone or in combination with nitrosourea-based chemotherapy: A clinical and pathological study,"A retrospective clinical and pathological study of 4 patients who developed the syndrome of radiation induced dementia was performed. All patients fulfilled the following criteria: (1) a history of supratentorial irradiation; (2) no evidence of symptomatic recurrent tumor; (3) no other cause of progressive cerebral dysfunction and dementia. The clinical picture consisted of a progressive 'subcortical' dementia occurring 3-12 months after a course of cerebral radiotherapy. Examination revealed early bilateral corticospinal tract involvement in all patients and dopa-resistant Parkinsonian syndrome in two. On CT scan and MRI of the brain, the main features consisted of progressive enlargement of the ventricles associated with a diffuse hypodensity/hyperintensity of the white matter best seen on T2 weighted images on MRI. The course was progressive over 8-48 months in 3 patients while one patient had stabilization of his condition for about 28 years. Treatment with corticosteroids or shunting did not produce sustained improvement and all patients eventually died. Pathological examination revealed diffuse white matter pallor with sparing of the arcuate fibers in all patients. Despite a common pattern on gross examination, microscopic studies revealed a variety of lesions that took two basic forms: (1) a diffuse axonal and myelin loss in the white matter associated with tissue necrosis, particularly multiple small foci of necrosis disseminated in the white matter which appeared different from the usual 'radionecrosis'; (2) diffuse spongiosis of the white matter characterized by the presence of vacuoles that displaced the normally-stained myelin sheets and axons. Despite a rather stereotyped clinical and radiological course, the pathological substratum of radiation-induced dementia is not uniform. Whether the different types of white matter lesions represent the spectrum of a single pathological process or indicate that the pathogenesis of this syndrome is multifactorial with different target cells, remains to be seen.",,"Vigliani, M. C.;Duyckaerts, C.;Hauw, J. J.;Poisson, M.;Magdelenat, H.;Delattre, J. Y.",1999,1999,,0,
543,Blue rubber bleb nevus syndrome in a patient with ataxia and dementia,"Blue rubber bleb nevus syndrome (BRBNS), an uncommon disorder characterized by cavernous hemangiomas, most often of the skin and gastrointestinal tract, is usually diagnosed during childhood and young adulthood. We made this diagnosis in an octogenarian referred to a geriatric medicine clinic because of concerns about his ability to live independently. Ataxia, dementia, focal neurologic signs, and bluish/purplish vascular nodules on his lips, buccal mucosa, tongue, chest, and neck were noted on physical examination. Magnetic resonance imaging (MRI) revealed an old left parietal infarction, multiple cavernous hemangiomas most densely concentrated in the subcortical structures and cerebellum, and areas of hemosiderin deposition. Skin biopsy findings were consistent with hemangioma. The physical examination, MRI, and skin biopsy made a diagnosis of BRBNS likely. The patient's ataxia, dementia, and other neurologic signs can be explained by previous hemorrhage from the vascular malformations in his brain. Blue rubber bleb nevus syndrome is an uncommon cause of a relatively common geriatric syndrome presentation.",,"Vig, E. K.;Brodkin, K. I.;Raugi, G. J.;Gladstone, H.",2002,2002,,0,
544,"Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study","BACKGROUND AND PURPOSE: Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function. METHODS: This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function. RESULTS: Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes. CONCLUSIONS: In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.","Aged;Aged, 80 and over;Aging/genetics/pathology/*physiology;Brain/pathology/*physiology;Calcinosis/*epidemiology/genetics/pathology/physiopathology;Cognition Disorders/epidemiology/genetics/pathology;Cohort Studies;Coronary Artery Disease/*epidemiology/genetics/pathology/physiopathology;Coronary Vessels/pathology/*physiology;Cross-Sectional Studies;*Environment;Female;Genetic Predisposition to Disease/*epidemiology/genetics;Humans;Iceland/epidemiology;Magnetic Resonance Imaging;Male","Vidal, J. S.;Sigurdsson, S.;Jonsdottir, M. K.;Eiriksdottir, G.;Thorgeirsson, G.;Kjartansson, O.;Garcia, M. E.;van Buchem, M. A.;Harris, T. B.;Gudnason, V.;Launer, L. J.",2010,May,10.1161/strokeaha.110.579581,0,
545,A method to improve interrater reliability of visual inspection of brain MRI scans in dementia,"MR scanning is used in the clinical evaluation of patients with dementia but lacks a reliable method of visual inspection. Two neurologists conducted multiple pilot trials of alternate methods for visual inspection of MRIs, including methods that produced at least 75% interrater agreement in repeat trials, and selected a final method for rating ventricular:brain ratio (VBR), cortical atrophy, and white matter changes. Two other neurologists, new to the method, tested interrater reliability for each component of the method after a brief training session. The correlation of VBR measurement was 0.884 (p = 0.0001). The weighted kappa scores were 0.68 for overall frontal lobe atrophy, 0.38 for right temporal lobe atrophy, 0.20 for left temporal lobe atrophy, and 0.54 for parietal lobe atrophy. The weighted kappa scores were 0.77 for overall periventricular white matter hyperintensities and 0.72 for centrum semiovale hyperintensities. The proposed method may provide a rapid and reliable way to assess VBR, frontal lobe atrophy, parietal lobe atrophy, and white matter changes on brain MRIs in the evaluation of dementia, but it was less reliable for the assessment of temporal lobe atrophy.",article;brain atrophy;clinical feature;dementia;diagnostic accuracy;disease severity;human;image analysis;nuclear magnetic resonance imaging;priority journal;rating scale;reliability,"Victoroff, J.;Mack, W. J.;Grafton, S. T.;Schreiber, S. S.;Chui, H. C.",1994,,,0,
546,Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings,"Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.",Alzheimer-s Disease;Dementia,"Victoroff, J.;Lin, F. V.;Coburn, K. L.;Shillcutt, S. D.;Voon, V.;Ducharme, S.",2018,Winter,,0,
547,The contribution of white matter lesions (WML) to Parkinson's disease cognitive impairment symptoms: A critical review of the literature,"We reviewed the impact of white matter lesions (WML) of cerebrovascular origin on cognitive impairment in Parkinson's disease (PD) patients. A search of PUBMED and Googlescholar.com revealed eleven studies that met the inclusion criteria: diagnosis based on the United Kingdom Brain Bank criteria (UK BBC); cognitive assessment; WML assessed on magnetic resonance imaging (MRI) by semiquantitative visual scales or automated method. Eight studies described the negative impact of WML on cognition in PD. Patients with mild cognitive impairment (MCI) and dementia had significantly more WML than the group without MCI and dementia. There was significant relationship between increasing total WML volume and worse performance on executive function, memory and language. Patients with vascular parkinsonism and dopaminergic denervation had more severe frontal lobe dysfunctions than patients with PD. In contrast in three studies there was no negative correlation between WML and cognition. Although the progression of neurodegenerative process in advanced stage of PD has been recognized as being mainly responsible for cognitive impairment in PD, WML may also be a contributing factor. It is possible that by reducing the vascular risk factors that cause WML cognitive impairment could be prevented or slowed down.",,"Vesely, B.;Rektor, I.",2016,Jan,10.1016/j.parkreldis.2015.09.019,0,
548,The contribution of white matter lesions to Parkinson's disease motor and gait symptoms: a critical review of the literature,"White matter lesions (WML) associated with cerebrovascular disease (CVD) may be observed on magnetic resonance imaging in Parkinson's disease (PD) patients. WML are an important factor contributing to postural, gait, and cognitive impairment in the elderly without PD and worsening the course of Alzheimer's disease (AD). Numerous articles are available on this topic. Whether WML modify and negatively influence the clinical symptoms, and course of PD is a subject of debate. The aim of this review is to examine the available literature on the contribution of WML to PD motor symptoms in relation to clinical characteristics and methods of assessing WML on MRI. After reviewing the database, we identified 19 studies reporting the relationship between WML and PD; ten studies focusing on the impact of WML on the cognitive status in PD were excluded. We analysed altogether nine studies reporting the relationship between WML and motor signs of PD. The review found association between WML severity and freezing of gait, less significant to responsiveness to dopaminergic treatment and postural instability; no negative impact on tremor and falls was observed. The impact of WML on bradykinesia and rigidity was inconsistent. Comorbid WML is associated with worsening axial motor performance, probably independently from the degree of nigrostriatal dopaminergic denervation in PD. Reducing the vascular risk factors that cause WML may be helpful in preventing the development of axial symptoms and ultimately in improving the quality of life of patients with PD. Given the lack of systematic studies, additional research in this field is needed.",,"Vesely, B.;Antonini, A.;Rektor, I.",2016,Mar,10.1007/s00702-015-1470-9,0,
549,Occurrence of Impaired Physical Performance in Memory Clinic Patients With Cerebral Small Vessel Disease,"Cerebral small vessel disease (CSVD) occurs often in memory clinic patients. Apart from cognitive deficits, these patients can express physical decline, which predicts adverse health outcomes. In this study, we investigated the cooccurrence of clinically relevant impairments in physical performance and CSVD in memory clinic patients. We included 131 patients with vascular brain injury, mild cognitive impairment or Alzheimer disease with available 3T MRI and physical performance scores. CSVD was visually rated according to 3 subtypes and as a total burden score, composed of the presence of white matter hyperintensities (WMH), lacunar infarcts (LI), and cerebral microbleeds (MB). Physical performance was assessed with the Short Physical Performance Battery (SPPB), covering gait speed, balance, and chair stand performance. CSVD markers and impaired physical performance both occurred often. High total CSVD burdens cooccurred with impaired chair stand performances [odds ratio (OR) 2.67; 95% confidence interval (CI) (1.12-6.34)]. WMH cooccurred with impaired SPPB scores (OR, 3.76; 95% CI, 1.68-8.44), impaired gait speeds (OR, 4.11; 95% CI, 1.81-9.31) and impaired chair stand performances (OR, 5.62; 95% CI, 2.29-13.80). In memory clinic patients, high burdens of CSVD, particularly WMH, often cooccur with impairments in physical performance. The presence of WMH should alert clinicians to the presence of these, clinically relevant, physical impairments.",,"Verwer, J. H.;Biessels, G. J.;Heinen, R.;Exalto, L. G.;Emmelot-Vonk, M. H.;Koek, H. L.;Utrecht Vascular Cognitive Impairment study, group",2017,Dec 13,,0,
550,CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): Diagnostic approaches and appropriate treatments,"CADASIL, acronym for &quot;cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy&quot; is the most common inherited cause of stroke. This condition gradually leads to vascular dementia. This case report draws attention to this disease, which is often under-diagnosed and must especially be considered in the absence of cardiovascular risk factors. This paper reports the case of a 62-year-old patient admitted to our unit for multiple stroke and transient ischemic attacks, with progressive dementia. MRI revealed multiple abnormalities suggestive of CADASIL. The physiopathology and management of this genetic arteriopathy, as well as the usefulness of further investigations, are discussed in this article, taking into account the most recent literature.",adult;article;CADASIL;case report;cerebrovascular accident;dementia;human;middle aged;nuclear magnetic resonance imaging;pathophysiology;transient ischemic attack,"Verstraete, G.;London, F.;Laloux, P.;Vandermeeren, Y.",2014,,,0,
551,Management of normal pressure hydrocephalus,"Gait instability, urinary incontinence, and dementia are the signs and symptoms typically found in patients who have normal pressure hydrocephalus. Estimated to cause no more than 5 percent of cases of dementia, normal pressure hydrocephalus often is treatable, and accurate recognition of the clinical triad coupled with radiographic evidence most commonly identifies likely responders. Magnetic resonance imaging or computed tomography typically demonstrates ventricular dilation with preservation of the surrounding brain tissue. The abnormality in normal pressure hydrocephalus occurs secondary to an abnormality in fluid removal, leading to an increase in ventricular size and encroachment of enlarged ventricles on adjacent brain tissue. The pressure exerted on the cerebral parenchyma by immense fluid-filled cavities deforms white matter tracts, instigating gait abnormalities and incomplete control of the bladder, as well as difficulties in processing incoming stimulation and in producing expeditious responses. Signs and symptoms often occur as sequelae to an imbalance between the expected ongoing production of cerebrospinal fluid and continuous efflux. Ventriculoperitoneal shunting is used to relieve excess ventricular fluid not absorbed by normal physiologic channels. Multiple studies have explored various techniques to identify patients with normal pressure hydrocephalus in an effort to predict likely benefit from shunting. However, the effectiveness of cerebrospinal fluid diversion has never been proven in a randomized controlled trial comparing use of a shunt versus no shunt.","Alzheimer Disease/diagnosis;Brain/pathology;Dementia/etiology;Gait Disorders, Neurologic/etiology;Humans;Hydrocephalus, Normal Pressure/diagnosis/physiopathology/ therapy;Intracranial Pressure;Magnetic Resonance Imaging;Ventriculoperitoneal Shunt","Verrees, M.;Selman, W. R.",2004,Sep 15,,0,
552,A novel hereditary small vessel disease of the brain,"Objective: Only few hereditary ischemic small vessel diseases of the brain (SVDB) have been reported so far. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent of them. Herein, we report a family affected by a SVDB distinct from CADASIL. Methods: After the occurrence of a small deep infarct associated with white matter lesions both in a 46-year-old man and in his 52-year-old sister, clinical and neuroimaging investigations were conducted in 13 of their relatives originating from Portugal. Other investigations included (1) skin biopsy immunostaining with a Notch3 monoclonal antibody, (2) sequencing of the 23 exons encoding the epidermal growth factor-like domains of the NOTCH3 gene, and (3) a NOTCH3 locus haplotype analysis. Results: Diffuse white matter hyperintensities were observed on T2-weighted magnetic resonance imaging (MRI) in six individuals. In contrast with MRI results in the father and paternal uncle of the proband who were hypertensive, white matter lesions were extensive in the mother who had no vascular risk factor. MRI data in four asymptomatic family members together with the results in the two initial cases were suggestive of an underlying hereditary small vessel disease of the brain. Skin biopsy and NOTCH3 gene mutation screening were negative. Haplotype analysis excluded the NOTCH3 locus. Interpretation: These data strongly suggest that this family is affected by a novel hereditary small vessel disease of the brainand that the mutated gene is distinct from NOTCH3. © 2006 American Neurological Association.",,"Verreault, S.;Joutel, A.;Riant, F.;Neves, G.;Silva, M. R.;Maciazek, J.;Tournier-Lasserve, E.;Bousser, M. G.;Chabriat, H.",2006,February,,0,
553,White matter microstructural integrity and cognitive function in a general elderly population,"CONTEXT: The role of macrostructural white matter changes, such as atrophy and white matter lesions, in cognitive decline is increasingly being recognized. However, in the elderly population, these macrostructural changes do not account for all variability in cognition. Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition. OBJECTIVE: To study the relation between white matter integrity and cognition in the general elderly population, using diffusion tensor imaging and taking into account macrostructural white matter changes. DESIGN: Cross-sectional population-based study. SETTING: A general community in the Netherlands. PARTICIPANTS: A population-based sample of 860 persons, older than 60 years, free of dementia. We performed multisequence magnetic resonance imaging, which included diffusion tensor imaging, and extensive neuropsychological testing. Fractional anisotropy, mean diffusivity, and directional diffusivities were measured globally in white matter lesions and normal-appearing white matter. MAIN OUTCOME MEASURES: Performance on neuropsychological tests in the following cognitive domains: memory, executive function, information processing speed, global cognition, and motor speed. RESULTS: Regardless of macrostructural white matter changes, a higher mean diffusivity or higher axial and radial diffusivities within white matter lesions or normal-appearing white matter were related to worse performance on tasks assessing information processing speed and global cognition. In addition, diffusivity within white matter lesions related to memory, while in normal-appearing white matter, it furthermore related to executive function. Lower mean fractional anisotropy in white matter lesions or normal-appearing white matter related to worse information processing speed and motor speed. CONCLUSIONS: Microstructural integrity of both white matter lesions and normal-appearing white matter is associated with cognitive function, regardless of white matter atrophy and white matter lesion volume. This suggests that measuring white matter integrity has added value beyond macrostructural assessment of white matter changes to study the relation between white matter and cognition.","Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Cognition Disorders/ pathology;Cohort Studies;Cross-Sectional Studies;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Netherlands;Neurodegenerative Diseases/ pathology;Neuropsychological Tests/ statistics & numerical data;Organ Size/physiology;Psychometrics;Reference Values;Temporal Lobe/pathology","Vernooij, M. W.;Ikram, M. A.;Vrooman, H. A.;Wielopolski, P. A.;Krestin, G. P.;Hofman, A.;Niessen, W. J.;Van der Lugt, A.;Breteler, M. M.",2009,May,10.1001/archgenpsychiatry.2009.5,0,
554,Superficial siderosis in the general population,"BACKGROUND: Superficial siderosis is a rare radiologic diagnosis of hemosiderin deposition in subpial brain layers. In case studies, an association between superficial siderosis and cerebral amyloid angiopathy (CAA) has been described. Also, a potential role of superficial siderosis in Alzheimer disease (AD) was hypothesized. All previously reported cases of superficial siderosis were detected because of overt clinical symptoms. We studied the occurrence of superficial siderosis on brain MRI in a general population of nondemented elderly. METHODS: In 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study, we performed T2*-weighted MRI to assess the presence of superficial siderosis. Furthermore, the presence, number, and location of cerebral microbleeds were rated, as lobar microbleeds are thought to be indicative of CAA. RESULTS: We found that superficial siderosis was present in 7 (0.7%) individuals, all of whom had cerebral microbleeds in lobar locations. Furthermore, in all 7 persons, microbleeds were located in close vicinity to superficial siderosis. CONCLUSIONS: Our results provide further indirect support for the presumed link between superficial siderosis and cerebral amyloid angiopathy (CAA). Whether superficial siderosis may be a marker for severity or worse prognosis of CAA needs to be further evaluated in longitudinal follow-up.","Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/pathology/physiopathology;Biomarkers/analysis/metabolism;Brain/blood supply/pathology/physiopathology;Cerebral Amyloid Angiopathy/*epidemiology/*pathology/physiopathology;Cerebral Arteries/pathology/physiopathology;Cohort Studies;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Prevalence;Prognosis;Siderosis/*epidemiology/*pathology/physiopathology;Subarachnoid Hemorrhage/*epidemiology/*pathology/physiopathology;Subarachnoid Space/pathology/physiopathology","Vernooij, M. W.;Ikram, M. A.;Hofman, A.;Krestin, G. P.;Breteler, M. M.;van der Lugt, A.",2009,Jul 21,10.1212/WNL.0b013e3181ae7c5e,0,
555,Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study,"BACKGROUND: Cerebral microbleeds are hemosiderin deposits in the brain that are indicative of microangiopathy. Microbleeds in strictly lobar brain locations have been related to cerebral amyloid angiopathy, a bleeding-prone disease state. OBJECTIVE: To investigate the relation between antithrombotic drug use and the presence of cerebral microbleeds, especially those in strictly lobar locations. DESIGN: A population-based, cross-sectional analysis that used magnetic resonance imaging (MRI) to assess the presence and location of microbleeds. Complete information on outpatient use of platelet aggregation inhibitors and anticoagulant drugs before MRI was obtained from automated pharmacy records. SETTING: The Rotterdam Scan Study, a population-based imaging study in a general elderly community in the Netherlands. PARTICIPANTS: A population-based sample of 1062 persons from a longitudinal cohort, 60 years and older, free of dementia, who underwent MRI examinations between August 15, 2005, and November 22, 2006. MAIN OUTCOME MEASURES: Presence of cerebral microbleeds on MRI. RESULTS: Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.21-2.41). We did not find a significant association for anticoagulant drugs and microbleed presence (OR, 1.49; 95% CI, 0.82-2.71). Strictly lobar microbleeds were more prevalent among aspirin users (adjusted OR compared with nonusers, 2.70; 95% CI, 1.45-5.04) than among persons using carbasalate calcium (adjusted OR, 1.16; 95% CI, 0.66-2.02). This difference was even more pronounced when comparing persons who had used similar dosages of both drugs. CONCLUSIONS: This cross-sectional study shows that use of platelet aggregation inhibitors is related to the presence of cerebral microbleeds. Furthermore, aspirin and carbasalate calcium use may differently relate to the presence of strictly lobar microbleeds.","Aged;Aged, 80 and over;Anticoagulants/adverse effects;Aspirin/adverse effects;Brain/blood supply/physiopathology;Cardiovascular Diseases/prevention & control;Causality;Cerebral Arteries/ drug effects/ pathology/physiopathology;Cerebral Hemorrhage/ chemically induced/ pathology/physiopathology;Cohort Studies;Cross-Sectional Studies;Dose-Response Relationship, Drug;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Microcirculation/ drug effects/physiology;Middle Aged;Netherlands;Platelet Aggregation Inhibitors/ adverse effects;Risk Factors","Vernooij, M. W.;Haag, M. D.;van der Lugt, A.;Hofman, A.;Krestin, G. P.;Stricker, B. H.;Breteler, M. M.",2009,Jun,10.1001/archneurol.2009.42,0,
556,6p25 microdeletion: White matter abnormalities in an adult patient,"We report on a 41-year-old woman of normal intelligence with a complicated past medical history including unilateral profound hearing loss, unilateral Axenfeld-Rieger anomaly, and leukoencephalopathy. She was referred to an adult neurology clinic because of a previous diagnosis of multiple sclerosis, which was non-responsive to multiple medications. Due to her complicated past medical history, the medical genetics service was consulted. She was found to have a chromosome 6p25.3-6p25.2 deletion on SNP array. This report highlights chromosome 6p subtelomeric deletions as a possible underlying cause for periventricular white matter abnormalities in an adult. It emphasizes the importance of genetic testing in an adult with leukoencephalopathy and congenital anomalies. © 2013 Wiley Periodicals, Inc.",beta1a interferon;glatiramer;natalizumab;adult;anamnesis;article;CADASIL;case report;chromosome analysis;chromosome deletion;chromosome deletion 6p25;differential diagnosis;disease course;disease exacerbation;disease severity;family history;female;human;image analysis;image processing;migraine;mixed hearing loss;multiple sclerosis;neuroimaging;nuclear magnetic resonance imaging;perception deafness;priority journal;single nucleotide polymorphism;white matter injury,"Vernon, H. J.;Bytyci Telegrafi, A.;Batista, D.;Owegi, M.;Leigh, R.",2013,,,0,
557,Evidence for atrophy of the corpus callosum in Alzheimer's disease,"Patients with late-onset Alzheimer's disease (AD) have more white matter changes on magnetic resonance imaging (MRI) than controls. To test the hypothesis that AD patients might have also atrophy of the corpus callosum (CC), we compared the CC thickness on MRI from 20 AD patients and 21 controls. We found a significant reduction in the CC thickness in AD compared with age-matched controls (p < 0.01). We demonstrated that atrophy of the CC depends mainly on the diagnosis of senile dementia of the Alzheimer type and at a lower degree on the diagnosis of presenile AD but neither on age nor on ventricle enlargement. This result suggests that beside the greater severity of white matter involvement in late-onset AD, atrophy of the CC may also be present.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Atrophy;Corpus Callosum/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Reference Values","Vermersch, P.;Scheltens, P.;Barkhof, F.;Steinling, M.;Leys, D.",1994,,,0,
558,White matter magnetic resonance imaging hyperintensity in Alzheimer's disease: correlations with corpus callosum atrophy,"We have previously demonstrated with MRI that as well as marked white matter involvement in late-onset Alzheimer's disease (AD), atrophy of the corpus callosum may also be present. This finding prompted us to study possible correlations between atrophy of the corpus callosum and white matter hyperintensity (WMH) and between white matter lesions and the severity of the disease. We compared the corpus callosum and white matter lesions on MRI from 15 AD patients and 15 controls. The white matter lesions were scored according to the Scheltens' rating scale. We found a significant reduction of the area of the corpus callosum and more severe white matter lesions in AD patients than in controls. Both atrophy of the corpus callosum and the severity of lesions depended mainly on the diagnosis of senile dementia of the Alzheimer type and on age but not on the diagnosis of presenile AD. We demonstrated a negative correlation between white matter lesions scores and areas of corpus callosum in AD patients and no correlation between the white matter lesions and the severity of the disease. We demonstrated that white matter lesions including WMH and atrophy of the corpus callosum are more frequent in AD than in controls. The predominance of white matter lesions in senile AD may be explained by the combination of aging and disease processes.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Atrophy;Case-Control Studies;Corpus Callosum/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Regression Analysis","Vermersch, P.;Roche, J.;Hamon, M.;Daems-Monpeurt, C.;Pruvo, J. P.;Dewailly, P.;Petit, H.",1996,Mar,,0,
559,"Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study","Silent brain infarcts and white matter lesions are frequently seen on magnetic resonance imaging in healthy elderly people and both are associated with an increased risk of stroke and dementia. Plasma total homocysteine may be a potentially modifiable risk factor for stroke and dementia. We examined whether elevated total homocysteine levels are associated with silent brain infarcts and white matter lesions. The Rotterdam Scan Study is a population-based study of 1,077 people aged 60 to 90 years who had cerebral magnetic resonance imaging. The cross-sectional relation of total homocysteine with silent infarcts and white matter lesions was analyzed with adjustment for cardiovascular risk factors. The mean plasma total homocystelne level was 11.5μmol/l (standard deviation 4.1). The risk of silent brain infarcts increased with increasing total homocysteine levels (odds ratio 1.24/standard deviation increase, 95% confidence interval 1.06-1.45). The severity of periventricular white matter lesions and extent of subcortical white matter lesions were also significantly associated with total homocysteine levels, even after excluding those with silent brain infarcts. The overall risk of having either a silent brain infarct or severe white matter lesions was strongly associated with total homocysteine levels (odds ratio 1.35/standard deviation increase, 95% confidence interval 1.16-1.58). We concluded that total homocysteine levels are associated with silent brain infarcts and white matter lesions independent of each other and of other cardiovascular risk factors.",,"Vermeer, S. E.;Van Dijk, E. J.;Koudstaal, P. J.;Oudkerk, M.;Hofman, A.;Clarke, R.;Breteler, M. M. B.",2002,2002,,0,
560,Silent brain infarcts and the risk of dementia and cognitive decline,"BACKGROUND: Silent brain infarcts are frequently seen on magnetic resonance imaging (MRI) in healthy elderly people and may be associated with dementia and cognitive decline. METHODS: We studied the association between silent brain infarcts and the risk of dementia and cognitive decline in 1015 participants of the prospective, population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia and stroke at base line. Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period. We performed Cox proportional-hazards and multiple linear-regression analyses, adjusted for age, sex, and level of education and for the presence or absence of subcortical atrophy and white-matter lesions. RESULTS: During 3697 person-years of follow-up (mean per person, 3.6 years), dementia developed in 30 of the 1015 participants. The presence of silent brain infarcts at base line more than doubled the risk of dementia (hazard ratio, 2.26; 95 percent confidence interval, 1.09 to 4.70). The presence of silent brain infarcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function. Silent thalamic infarcts were associated with a decline in memory performance, and nonthalamic infarcts with a decline in psychomotor speed. When participants with silent brain infarcts at base line were subdivided into those with and those without additional infarcts at follow-up, the decline in cognitive function was restricted to those with additional silent infarcts. CONCLUSIONS: Elderly people with silent brain infarcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions.","Aged;Aged, 80 and over;Brain Infarction/ complications/pathology;Cognition Disorders/diagnosis/ etiology;Dementia/diagnosis/ etiology;Female;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Proportional Hazards Models;Prospective Studies;Psychiatric Status Rating Scales;Recurrence;Risk Factors","Vermeer, S. E.;Prins, N. D.;den Heijer, T.;Hofman, A.;Koudstaal, P. J.;Breteler, M. M.",2003,Mar 27,10.1056/NEJMoa022066,1,
561,Progression of cerebral white matter lesions is not associated with development of depressive symptoms in elderly subjects at risk of cardiovascular disease. The PROSPER Study,"Background: Cerebral white matter hyperintensities on magnetic resonance imaging (MRI) scans have been associated with vascular disease and late-life depression, both in the general population and in psychiatric patients. Therefore, a cerebrovascular etiology for late-onset depression has been hypothesized. However, longitudinal studies on the causal role of white matter hyperintensities in the development of depressive symptoms in elderly adults are lacking. Objective: To investigate the relation between white matter hyperintensities and depressive symptoms in elderly subjects at risk of cardiovascular disease. Methods: In the Dutch sample of the PROSPER (PROspective Study of Pravastatine in the Elderly at Risk of cardiovascular disease) cohort, 527 non-demented elderly, all aged 70 years or older, received a cranial MRI scan and the 15-item Geriatric Depression Scale, at baseline and 33 months (SD 1.6) later. Results: Presence of white matter hyperintensities at baseline was not related to baseline depressive symptoms nor to the development of depressive symptoms during follow-up. Moreover, no association was found between progression of white matter lesion volume and progression of depressive symptoms. Conclusion: This longitudinal study does not confirm the involvement of cerebrovascular disease expressed as MRI white matter hyperintensities in the development of depressive symptoms in elderly subjects. Copyright © 2006 John Wiley & Sons, Ltd.",,"Verluis, C. E.;van der Mast, R. C.;van Buchem, M. A.;Bollen, E. L. E. M.;Blauw, G. J.;Eekhof, J. A. H.;van der Wee, N. J. A.;de Craen, A. J. M.;Shepherd, J.;Cobbe, S. M.;Ford, I.;Gaw, A.;Macfarlane, P. W.;Packard, C. J.;Stott, D. J.;Kamper, A. M.;Westendorf, R. G. J.;Murphy, M. B.;Buckely, B. M.;Hyland, M.;Perry, I. J.;Jukema, W. J.;Meinders, A. E.;Sweeney, B. J.;Twomey, C.",2006,April,,0,
562,Brain MRI-markers Associate Differentially with Cognitive Versus Functional Decline Leading to Dementia,"BACKGROUND: Brain MRI-markers are risk factors of dementia and decline in cognition and daily functioning. It is unknown to what extent the associations of brain MRI-markers with cognition and daily functioning are part of the pathway leading to dementia. We aimed to investigate associations of brain MRI-markers with change in cognition and daily functioning during 15 years of follow-up, including their relation to dementia. DESIGN, SETTING, AND PARTICIPANTS: Four hundred and sixty three stroke-free and non-demented participants from the population-based Rotterdam Study that underwent brain-MRI, yielding brain volumetrics, between 1995 and 1996. MEASUREMENTS: We assessed cognition using the Mini-Mental State Examination (MMSE) and daily functioning using instrumental and basic activities of daily living (IADL and BADL) up to seven times between 1990 and 2011. Analyses were performed both including and excluding incident demented participants. RESULTS: Smaller brain volume associated with larger decline in MMSE, IADL, and BADL. Larger white matter lesion volume associated with larger decline in MMSE. Frontal lobe volume associated strongest with decline in IADL and BADL, and temporal lobe volume with decline in MMSE. After excluding incident demented participants (n = 63), associations with IADL and BADL remained, while associations with MMSE disappeared. CONCLUSIONS: Smaller brain volumes and larger white matter volume associate with larger decline in cognition and daily functioning, during 15 years of follow-up. Importantly, the relation of brain volume with cognition, but not daily functioning, was driven by those individuals that ultimately developed dementia.",Activities of Daily Living;Aged;Brain/ pathology;Cognition;Cognition Disorders/diagnosis;Dementia/diagnosis;Disease Progression;Female;Humans;Independent Living;Longitudinal Studies;Magnetic Resonance Imaging/ statistics & numerical data;Male;Netherlands;Neuropsychological Tests/statistics & numerical data;Mri;brain;dementia,"Verlinden, V. J. A.;van der Geest, J. N.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Vernooij, M. W.;Ikram, M. A.",2017,Jun,,0,
563,Brain MRI-markers Associate Differentially with Cognitive Versus Functional Decline Leading to Dementia,"BACKGROUND: Brain MRI-markers are risk factors of dementia and decline in cognition and daily functioning. It is unknown to what extent the associations of brain MRI-markers with cognition and daily functioning are part of the pathway leading to dementia. We aimed to investigate associations of brain MRI-markers with change in cognition and daily functioning during 15 years of follow-up, including their relation to dementia. DESIGN, SETTING, AND PARTICIPANTS: Four hundred and sixty three stroke-free and non-demented participants from the population-based Rotterdam Study that underwent brain-MRI, yielding brain volumetrics, between 1995 and 1996. MEASUREMENTS: We assessed cognition using the Mini-Mental State Examination (MMSE) and daily functioning using instrumental and basic activities of daily living (IADL and BADL) up to seven times between 1990 and 2011. Analyses were performed both including and excluding incident demented participants. RESULTS: Smaller brain volume associated with larger decline in MMSE, IADL, and BADL. Larger white matter lesion volume associated with larger decline in MMSE. Frontal lobe volume associated strongest with decline in IADL and BADL, and temporal lobe volume with decline in MMSE. After excluding incident demented participants (n = 63), associations with IADL and BADL remained, while associations with MMSE disappeared. CONCLUSIONS: Smaller brain volumes and larger white matter volume associate with larger decline in cognition and daily functioning, during 15 years of follow-up. Importantly, the relation of brain volume with cognition, but not daily functioning, was driven by those individuals that ultimately developed dementia.",Mri;activities of daily living;brain;cognition;dementia,"Verlinden, V. J.;van der Geest, J. N.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Vernooij, M. W.;Ikram, M. A.",2017,Feb 06,,0,
564,Structural and microstructural brain changes predict impairment in daily functioning,"BACKGROUND: Brain changes on magnetic resonance imaging (MRI) reflect accumulating pathology and have clinically disabling consequences, such as dementia. However, little is known on the relation of these MRI markers with daily functioning in nondemented individuals. We investigated whether structural and microstructural brain changes are associated with impairment in activities of daily living in a community-dwelling population. METHODS: Between 2005 and 2009, 2025 stroke-free nondemented participants (aged 59.9 years) from the population-based Rotterdam Study underwent brain MRI, yielding global MRI markers, focal MRI markers, and microstructural MRI markers. We used the Stanford Health Assessment Questionnaire to assess basic activities of daily living, and the Instrumental Activities of Daily Living Scale to assess instrumental activities of daily living. Follow-up on activities of daily living was obtained between 2008 and 2013 (mean follow-up 5.7 years). We used linear regression to analyze continuous scores of daily living and logistic regression for incident impairment. RESULTS: Eighty-two participants became impaired in basic and 33 in instrumental activities of daily living. Smaller brain and hippocampal volume and higher diffusivity were associated with larger change in activities of daily living. Smaller brain volume (odds ratio [OR] 4.05 per SD; 95% confidence interval [CI], 1.81-9.02), larger white matter lesion volume (OR 1.33/SD; 95% CI 1.02-1.72) and higher mean (OR 1.55/SD; 95% CI, 1.11-2.15), axial (OR 1.49/SD; 95% CI, 1.08-2.07), and radial diffusivity (OR 1.51/SD; 95% CI, 1.09-2.10) were associated with higher risk of impairment in basic activities of daily living. CONCLUSIONS: In community-dwelling individuals, brain changes are associated with deterioration and incident impairment in daily functioning.",Activities of Daily Living;Atrophy;Brain/ pathology;Disability Evaluation;Female;Follow-Up Studies;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged,"Verlinden, V. J.;van der Geest, J. N.;de Groot, M.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Vernooij, M. W.;Ikram, M. A.",2014,Nov,10.1016/j.amjmed.2014.06.037,0,
565,Tract-specific white matter microstructure and gait in humans,"Gait is a complex sequence of movements, requiring cooperation of many brain areas, such as the motor cortex, somatosensory cortex, and cerebellum. However, it is unclear which connecting white matter tracts are essential for communication across brain areas to facilitate proper gait. Using diffusion tensor imaging, we investigated associations of microstructural organization in 14 brain white matter tracts with gait, among 2330 dementia- and stroke-free community-dwelling individuals. Gait was assessed by electronic walkway and summarized into Global Gait, and 7 gait domains. Higher white matter microstructure associated with higher Global Gait, Phases, Variability, Pace, and Turning. Microstructure in thalamic radiations, followed by association tracts and the forceps major, associated most strongly with gait. Hence, in community-dwelling individuals, higher white matter microstructure associated with better gait, including larger strides, more single support, less stride-to-stride variability, and less turning steps. Our findings suggest that intact thalamocortical communication, cortex-to-cortex communication, and interhemispheric visuospatial integration are most essential in human gait.",Brain white matter tracts;Diffusion tensor imaging;Gait;Magnetic resonance imaging;Walking,"Verlinden, V. J.;de Groot, M.;Cremers, L. G.;van der Geest, J. N.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Vernooij, M. W.;Ikram, M. A.",2016,Jul,10.1016/j.neurobiolaging.2016.04.005,0,
566,New phenotype of the cerebral autosomal dominant arteriopathy mapped to chromosome 19: Migraine as the prominent clinical feature,"A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts developing into pseudobulbar palsy and subcortical dementia, and radiologically by early MRI abnormalities. To characterise this familial condition, 43 members older than 20 years and spreading over four generations were studied clinically (31 living, 12 deceased), genetically, and radiologically by MRI (n = 31). Twenty out of 43 were found to be clinically symptomatic and of these 13 out of 31 had MRI abnormalities. Genetic studies mapped this condition to the locus of CADASIL (lod score > 3). The natural history suggests a chronological clinicoradiological staging of this phenotype of CADASIL: stage I between 20 and 40 years with frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episodes, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar palsy, diffuse leukoencephalopathy, and multiple well delineated lesions of the basal ganglia. This phenotype differs from the other two previously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym ((cerebral autosomal dominant arteriopathy with subcortical infarcts, leukoencephalopathy, and migraine' (CADASILM) is proposed to better describe this particular subvariety of CADASIL.",adult;article;autosomal dominant inheritance;basal ganglion;brain infarction;cerebrovascular disease;chromosome 19;clinical feature;dementia;family;gene locus;gene mapping;human;leukoencephalopathy;major clinical study;migraine;nuclear magnetic resonance imaging;paralysis;phenotype;priority journal;psychosis;cerebrovascular accident;white matter,"Verin, M.;Rolland, Y.;Landgraf, F.;Chabriat, H.;Bompais, B.;Michel, A.;Vahedi, K.;Martinet, J.;Tournier-Lasserve, E.;Lemaitre, M. H.;Eden, G.",1995,,,0,
567,The impact of MRI combined with visual rating scales on the clinical diagnosis of dementia: a prospective study,"OBJECTIVES: Dementia is foremost a clinical diagnosis. However, in diagnosing dementia, it is advocated to perform at least one neuroimaging study. This has two purposes: to rule out potential reversible dementia (PRD), and to help determine the dementia subtype. Our first goal was to establish if MRI combined with visual rating scales changes the clinical diagnosis. The second goal was to demonstrate if MRI contributes to a geriatrician's confidence in the diagnosis. METHODS: The dementia subtype was determined prior to and after MRI. Scoring scales used were: global cortical atrophy (GCA), medial temporal atrophy (MTA), and white matter hyperintensity measured according to the Fazekas scale. The confidence level of the geriatrician was determined using a visual analogue scale. RESULTS: One hundred and thirty-five patients were included. After MRI, the diagnosis changed in 23.7 % (CI 17.0 %-31.1 %) of patients. Change was due to vascular aetiology in 13.3 % of patients. PRD was found in 2.2 % of all patients. The confidence level in the diagnosis increased significantly after MRI (p = 0.001). CONCLUSIONS: MRI, combined with visual rating scales, has a significant impact on dementia subtype diagnosis and on a geriatrician's confidence in the final diagnosis. KEY POINTS: * MRI with visual rating scales changes the dementia subtype diagnosis significantly. * MRI is essential in demonstrating vascular disease as a cause of dementia. * All suspected dementia patients should undergo an MRI with visual rating scales. * MRI improves a geriatrician's confidence in the diagnosis of the dementia subtype. * MRI remains essential during the workup of dementia to exclude reversible causes.",Aged;Alzheimer Disease/diagnosis;Atrophy/pathology;Dementia/ diagnosis;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neurodegenerative Diseases/pathology;Neuroimaging/methods;Prospective Studies;Temporal Lobe/ pathology;Visual Analog Scale;Alzheimer's disease;Dementia;Magnetic resonance imaging;Mild cognitive impairment;Vascular,"Verhagen, M. V.;Guit, G. L.;Hafkamp, G. J.;Kalisvaart, K.",2016,Jun,,0,568
568,The impact of MRI combined with visual rating scales on the clinical diagnosis of dementia: a prospective study,"OBJECTIVES: Dementia is foremost a clinical diagnosis. However, in diagnosing dementia, it is advocated to perform at least one neuroimaging study. This has two purposes: to rule out potential reversible dementia (PRD), and to help determine the dementia subtype. Our first goal was to establish if MRI combined with visual rating scales changes the clinical diagnosis. The second goal was to demonstrate if MRI contributes to a geriatrician's confidence in the diagnosis. METHODS: The dementia subtype was determined prior to and after MRI. Scoring scales used were: global cortical atrophy (GCA), medial temporal atrophy (MTA), and white matter hyperintensity measured according to the Fazekas scale. The confidence level of the geriatrician was determined using a visual analogue scale. RESULTS: One hundred and thirty-five patients were included. After MRI, the diagnosis changed in 23.7 % (CI 17.0 %-31.1 %) of patients. Change was due to vascular aetiology in 13.3 % of patients. PRD was found in 2.2 % of all patients. The confidence level in the diagnosis increased significantly after MRI (p = 0.001). CONCLUSIONS: MRI, combined with visual rating scales, has a significant impact on dementia subtype diagnosis and on a geriatrician's confidence in the final diagnosis. KEY POINTS: * MRI with visual rating scales changes the dementia subtype diagnosis significantly. * MRI is essential in demonstrating vascular disease as a cause of dementia. * All suspected dementia patients should undergo an MRI with visual rating scales. * MRI improves a geriatrician's confidence in the diagnosis of the dementia subtype. * MRI remains essential during the workup of dementia to exclude reversible causes.",,"Verhagen, M. V.;Guit, G. L.;Hafkamp, G. J.;Kalisvaart, K.",2015,Aug 29,10.1007/s00330-015-3957-z,0,
569,Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI,"BACKGROUND: The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. METHODS AND RESULTS: We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7x10(-19)) and identified novel loci on chr10q24 (P=1.6x10(-9)) and chr2p21 (P=4.4x10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0x10(-8)) and chr2p16 (P=1.5x10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). CONCLUSIONS: We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.","Aged;Aged, 80 and over;Chromosomes, Human/genetics;*Continental Population Groups;Female;*Genetic Loci;*Genome-Wide Association Study;Humans;Male;Meta-Analysis as Topic;Middle Aged;*Models, Genetic;*Stroke/ethnology/genetics/pathology;*White Matter;cerebral small vessel diseases;cerebrovascular disorders;genome-wide association study;hypertension;leukoencephalopathies;polymorphisms, single nucleotide","Verhaaren, B. F.;Debette, S.;Bis, J. C.;Smith, J. A.;Ikram, M. K.;Adams, H. H.;Beecham, A. H.;Rajan, K. B.;Lopez, L. M.;Barral, S.;van Buchem, M. A.;van der Grond, J.;Smith, A. V.;Hegenscheid, K.;Aggarwal, N. T.;de Andrade, M.;Atkinson, E. J.;Beekman, M.;Beiser, A. S.;Blanton, S. H.;Boerwinkle, E.;Brickman, A. M.;Bryan, R. N.;Chauhan, G.;Chen, C. P.;Chouraki, V.;de Craen, A. J.;Crivello, F.;Deary, I. J.;Deelen, J.;De Jager, P. L.;Dufouil, C.;Elkind, M. S.;Evans, D. A.;Freudenberger, P.;Gottesman, R. F.;Guethnason, V.;Habes, M.;Heckbert, S. R.;Heiss, G.;Hilal, S.;Hofer, E.;Hofman, A.;Ibrahim-Verbaas, C. A.;Knopman, D. S.;Lewis, C. E.;Liao, J.;Liewald, D. C.;Luciano, M.;van der Lugt, A.;Martinez, O. O.;Mayeux, R.;Mazoyer, B.;Nalls, M.;Nauck, M.;Niessen, W. J.;Oostra, B. A.;Psaty, B. M.;Rice, K. M.;Rotter, J. I.;von Sarnowski, B.;Schmidt, H.;Schreiner, P. J.;Schuur, M.;Sidney, S. S.;Sigurdsson, S.;Slagboom, P. E.;Stott, D. J.;van Swieten, J. C.;Teumer, A.;Toglhofer, A. M.;Traylor, M.;Trompet, S.;Turner, S. T.;Tzourio, C.;Uh, H. W.;Uitterlinden, A. G.;Vernooij, M. W.;Wang, J. J.;Wong, T. Y.;Wardlaw, J. M.;Windham, B. G.;Wittfeld, K.;Wolf, C.;Wright, C. B.;Yang, Q.;Zhao, W.;Zijdenbos, A.;Jukema, J. W.;Sacco, R. L.;Kardia, S. L.;Amouyel, P.;Mosley, T. H.;Longstreth, W. T., Jr.;DeCarli, C. C.;van Duijn, C. M.;Schmidt, R.;Launer, L. J.;Grabe, H. J.;Seshadri, S. S.;Ikram, M. A.;Fornage, M.",2015,Apr,10.1161/circgenetics.114.000858,0,
570,Heterozygous HTRA1 mutations are associated with autosomal dominant cerebral small vessel disease,"Cerebral small vessel disease represents a heterogeneous group of disorders leading to stroke and cognitive impairment. While most small vessel diseases appear sporadic and related to age and hypertension, several early-onset monogenic forms have also been reported. However, only a minority of patients with familial small vessel disease carry mutations in one of known small vessel disease genes. We used whole exome sequencing to identify candidate genes in an autosomal dominant small vessel disease family in which known small vessel disease genes had been excluded, and subsequently screened all candidate genes in 201 unrelated probands with a familial small vessel disease of unknown aetiology, using high throughput multiplex polymerase chain reaction and next generation sequencing. A heterozygous HTRA1 variant (R166L), absent from 1000 Genomes and Exome Variant Server databases and predicted to be deleterious by in silico tools, was identified in all affected members of the index family. Ten probands of 201 additional unrelated and affected probands (4.97%) harboured a heterozygous HTRA1 mutation predicted to be damaging. There was a highly significant difference in the number of likely deleterious variants in cases compared to controls (P = 4.2 × 10<sup>-6</sup>; odds ratio = 15.4; 95% confidence interval = 4.9-45.5), strongly suggesting causality. Seven of these variants were located within or close to the HTRA1 protease domain, three were in the N-terminal domain of unknown function and one in the C-terminal PDZ domain. In vitro activity analysis of HTRA1 mutants demonstrated a loss of function effect. Clinical features of this autosomal dominant small vessel disease differ from those of CARASIL and CADASIL by a later age of onset and the absence of the typical extraneurological features of CARASIL. They are similar to those of sporadic small vessel disease, except for their familial nature. Our data demonstrate that heterozygous HTRA1 mutations are an important cause of familial small vessel disease, and that screening of HTRA1 should be considered in all patients with a hereditary small vessel disease of unknown aetiology.",proteinase;adult;aged;amino terminal sequence;article;autosomal dominant disorder;autosomal recessive disorder;CADASIL;carboxy terminal sequence;cerebral autosomal recessive arteriopathy with subcortical infarct and leucoencephalopathy;cerebrovascular disease;clinical feature;computer model;controlled study;data base;exome;familial disease;family;female;gene;gene mutation;genetic association;genetic screening;heterozygote;high throughput sequencing;HTRA1 gene;human;human cell;in vitro study;linkage analysis;major clinical study;male;middle aged;multiplex polymerase chain reaction;mutational analysis;next generation sequencing;nuclear magnetic resonance imaging;onset age;PDZ domain;phylogeny;priority journal;sequence analysis,"Verdura, E.;Hervé, D.;Scharrer, E.;Amador, M. D. M.;Guyant-Maréchal, L.;Philippi, A.;Corlobé, A.;Bergametti, F.;Gazal, S.;Prieto-Morin, C.;Beaufort, N.;Le Bail, B.;Viakhireva, I.;Dichgans, M.;Chabriat, H.;Haffner, C.;Tournier-Lasserve, E.",2015,,,0,
571,Self-perceived memory complaints predict progression to Alzheimer disease. the LADIS study,"Memory complaints are frequent in the elderly but its implications in cognition over time remain a controversial issue. Our objective was to evaluate the risk of self perceived memory complaints in the evolution for future dementia. The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes (WMC) on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Dementia and subtypes of dementia were classified. Self perceived memory complaints in independent elderly were collected during the interview. MRI was performed at entry and at the end of the study. 639 subjects were included (74.1 ± 5 years old, 55% women, 9.6 ± 3.8 years of schooling). At end of follow-up, 90 patients were demented (vascular dementia, 54; Alzheimer's disease (AD) and AD with vascular component, 34; frontotemporal dementia, 2). Using Cox regression analysis, we found that self perceived memory complaints were a strong predictor of AD and AD with vascular component during the follow-up (β = 2.7, p = 0.008; HR = 15.5, CI 95% [2.04, 117.6]), independently of other confounders, namely depressive symptoms, WMC severity, medial temporal lobe atrophy, and global cognition status at baseline. Self perceived memory complaints did not predict vascular dementia. In the LADIS study, self perceived memory complaints predicted AD but not vascular dementia in elderly subjects with WMC living independently. © 2011 - IOS Press and the authors. All rights reserved.",aged;aging;Alzheimer disease;article;brain atrophy;dementia;depression;disability;disease course;disease severity;Europe;female;follow up;geriatric patient;human;leukoaraiosis;major clinical study;male;memory disorder;Mini Mental State Examination;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;perception;prediction;priority journal;prospective study;temporal lobe;white matter,"Verdelho, A.;Madureira, S.;Moleiro, C.;Santos, C. O.;Ferro, J. M.;Erkinjuntti, T.;Poggesi, A.;Pantoni, L.;Fazekas, F.;Scheltens, P.;Waldemar, G.;Wallin, A.;Inzitari, D.",2011,,,0,
572,White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study,"OBJECTIVE: We aimed to study if age-related white matter changes (WMC) and vascular risk factors were predictors of cognitive decline in elderly subjects with WMC living independently. METHODS: The Leukoaraiosis and Disability prospective multinational European study (LADIS) evaluates the impact of WMC on the transition of independent elderly subjects into disability. Independent elderly were enrolled due to the presence of WMC. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and a neuropsychological battery. Additionally, dementia, subtypes of dementia, and cognitive decline without dementia were classified according to usual clinical criteria. MRI was performed at entry and at the end of the study. RESULTS: A total of 639 subjects were included (74.1 +/- 5 years, 55% women, 9.6 +/- 3.8 years of schooling). At end of follow-up, 90 patients had dementia and 147 had cognitive impairment no dementia. Using Cox regression analysis, WMC severity independently predicted cognitive decline (dementia and not dementia), independently of age, education, and medial temporal atrophy (MTA). Diabetes at baseline was the only vascular risk factor that independently predicted cognitive decline during follow-up, controlling for age, education, WMC severity, and temporal atrophy. Considering subtypes of dementia, Alzheimer disease (AD) was predicted only by MTA, while vascular dementia was predicted by previous stroke, WMC severity, and MTA. CONCLUSION: WMC severity and diabetes are independent predictors of cognitive decline in an initially nondisabled elderly population. Vascular dementia is predicted by previous stroke and WMC, while AD is predicted only by MTA.","Activities of Daily Living;Age Factors;Aged;Aged, 80 and over;Aging/pathology;Atrophy/pathology;Brain/*pathology;Cognition Disorders/complications/diagnosis/*pathology;Diabetes Mellitus, Type 2/complications/*pathology;Disability Evaluation;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Patient Selection;Proportional Hazards Models;Prospective Studies;Risk Factors;Severity of Illness Index","Verdelho, A.;Madureira, S.;Moleiro, C.;Ferro, J. M.;Santos, C. O.;Erkinjuntti, T.;Pantoni, L.;Fazekas, F.;Visser, M.;Waldemar, G.;Wallin, A.;Hennerici, M.;Inzitari, D.",2010,Jul 13,10.1212/WNL.0b013e3181e7ca05,0,
573,Depressive symptoms predict cognitive decline and dementia in older people independently of cerebral white matter changes: the LADIS study,"OBJECTIVE: Depressive symptoms (DS) have been associated with increased risk of cognitive decline. Our aim was to evaluate the longitudinal influence of DS on cognition in independent older people, accounting for the severity of white matter changes (WMC). METHODS: The LADIS (Leukoaraiosis And DISability in the elderly) prospective study evaluated the impact of WMC on the transition of independent older subjects into disability. Subjects were evaluated annually over a 3 year period with a comprehensive clinical and neuropsychological evaluation. Previous episodes of depression and current DS were assessed during each interview. Severity of DS was assessed using the self-rated 15 item Geriatric Depression Scale. A neuropsychological battery and clinical criteria for cognitive impairments were applied in all clinical visits, and cognitive compound measures were made based on neuropsychological results. MRI was performed at baseline and at year 3. RESULTS: 639 subjects were included (74.1 +/- 5 years old, 55% women, 9.6 +/- 3.8 years of schooling). Dementia was diagnosed in 90 patients and cognitive impairment not dementia in 147 patients at the last clinical evaluation. DS were an independent predictor of cognitive impairment (dementia and not dementia) during follow-up, independent of the effect of the severity of WMC, medial temporal lobe atrophy, age, education or global cognitive function at baseline. CONCLUSIONS: DS are associated with an increase risk of cognitive decline, independent of the effect of WMC, probably due to an additive or synergistic effect. In this context, DS probably represent a subtle ongoing organic dysfunction.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/epidemiology/psychology;Animals;Brain/pathology;Depressive Disorder/*diagnosis/epidemiology/psychology;Disease Progression;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/*diagnosis/epidemiology/psychology;Neuropsychological Tests/statistics & numerical data;Psychometrics;Risk Assessment;White Muscle Disease/*diagnosis/epidemiology/psychology;Cerebrovascular Disease;Cognition;Dementia;Depression","Verdelho, A.;Madureira, S.;Moleiro, C.;Ferro, J. M.;O'Brien, J. T.;Poggesi, A.;Pantoni, L.;Fazekas, F.;Scheltens, P.;Waldemar, G.;Wallin, A.;Erkinjuntti, T.;Inzitari, D.",2013,Nov,10.1136/jnnp-2012-304191,0,
574,"Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study","BACKGROUND AND PURPOSE: Age related white matter changes (ARWMC) are frequent in non-demented old subjects and are associated with impaired cognitive function. Our aim was to study the influence of vascular risk factors and ARWMC on the neuropsychological performance of an independent elderly population, to see if vascular risk factors impair cognition in addition to the effects of ARWMC. METHODS: Independent subjects, aged 65-84 years, with any degree of ARWMC were assessed using a comprehensive neuropsychological battery including the Mini-Mental State Examination (MMSE), VADAS-Cog (Alzheimer's disease assessment scale) and the Stroop and Trail Making test. Vascular risk factors were recorded and ARWMC (measured by MRI) were graded into three classes. The impact of vascular risk factors and ARWMC on neuropsychological performance was assessed by linear regression analyses, with adjustment for age and education. RESULTS: 638 patients (74.1 (5) years old, 55% women) were included. Patients with severe ARWMC performed significantly worse on global tests of cognition, executive functions, speed and motor control, attention, naming and visuoconstructional praxis. Diabetes interfered with tests of executive function, attention, speed and motor control, memory and naming. Arterial hypertension and stroke influenced executive functions and attention. The effect of these vascular risk factors was independent of the severity of ARWMC, age and education. CONCLUSION: ARWMC is related to worse performance in executive function, attention and speed. Diabetes, hypertension and previous stroke influenced neuropsychological performance, independently of the severity of ARWMC, stressing the need to control vascular risk factors in order to prevent cognitive decline in the elderly.","Activities of Daily Living;Aged;Aged, 80 and over;Alcohol Drinking/epidemiology;Alzheimer Disease/diagnosis/epidemiology;Blood Glucose/metabolism;Brain/blood supply/*pathology;Cerebrovascular Circulation/physiology;Cognition Disorders/diagnosis/*epidemiology/*etiology;Diabetes Mellitus, Type 2/diagnosis/drug therapy/*epidemiology;Disability Evaluation;Female;Humans;Hypertension/*epidemiology;Hypoglycemic Agents/therapeutic use;Magnetic Resonance Imaging;Male;Mass Screening/methods;Neuropsychological Tests;Prevalence;Risk Factors;Severity of Illness Index;*Stroke/complications/epidemiology/pathology;Surveys and Questionnaires;Trail Making Test","Verdelho, A.;Madureira, S.;Ferro, J. M.;Basile, A. M.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Hennerici, M.;O'Brien, J.;Pantoni, L.;Salvadori, E.;Scheltens, P.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Inzitari, D.",2007,Dec,10.1136/jnnp.2006.110361,0,
575,Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study,"BACKGROUND AND PURPOSE: We aimed to study if physical activity could interfere with progression for cognitive impairment and dementia in older people with white matter changes living independently. METHODS: The LADIS (Leukoaraiosis and Disability) prospective multinational European study evaluates the impact of white matter changes on the transition of independent elderly subjects into disability. Subjects were evaluated yearly during 3 years with a comprehensive clinical protocol and cognitive assessment with classification of cognitive impairment and dementia according to usual clinical criteria. Physical activity was recorded during the clinical interview. MRI was performed at entry and at the end of the study. RESULTS: Six hundred thirty-nine subjects were included (74.1+/-5 years old, 55% women, 9.6+/-3.8 years of schooling, 64% physically active). At the end of follow-up, 90 patients had dementia (vascular dementia, 54; Alzheimer disease with vascular component, 34; frontotemporal dementia, 2), and 147 had cognitive impairment not dementia. Using Cox regression analysis, physical activity reduced the risk of cognitive impairment (dementia and not dementia: beta=-0.45, P=0.002; hazard ratio, 0.64; 95% CI, 0.48-0.85), dementia (beta=-0.49, P=0.043; hazard ratio, 0.61; 95% CI, 0.38-0.98), and vascular dementia (beta=-0.86, P=0.008; hazard ratio, 0.42; 95% CI, 0.22-0.80), independent of age, education, white matter change severity, medial temporal atrophy, previous and incident stroke, and diabetes. CONCLUSIONS: Physical activity reduces the risk of cognitive impairment, mainly vascular dementia, in older people living independently.","Activities of Daily Living;Aged;Alzheimer Disease/epidemiology/physiopathology/prevention & control;Cognition Disorders/epidemiology/*physiopathology/*prevention & control;Dementia, Vascular/epidemiology/*physiopathology/*prevention & control;Diabetes Mellitus/epidemiology;Disability Evaluation;Disease Progression;Female;Humans;Incidence;Interviews as Topic;Leukoencephalopathies/epidemiology/physiopathology/prevention & control;Magnetic Resonance Imaging;Male;Motor Activity/*physiology;Neuropsychological Tests;Prospective Studies;Risk Factors;Stroke/epidemiology;Temporal Lobe/pathology/physiopathology","Verdelho, A.;Madureira, S.;Ferro, J. M.;Baezner, H.;Blahak, C.;Poggesi, A.;Hennerici, M.;Pantoni, L.;Fazekas, F.;Scheltens, P.;Waldemar, G.;Wallin, A.;Erkinjuntti, T.;Inzitari, D.",2012,Dec,10.1161/strokeaha.112.661793,0,
576,The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neurological disorders,"Chronic microglial activation is an important component of many neurological disorders, and imaging activated microglia in vivo will enable the detection and improved treatment of neuroinflammation. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carbox-amide (PK11195), a peripheral benzodiazepine receptor ligand, has been used to image neuroinflammation, but the extent to which PK11195 binding distinguishes activated microglia and reactive astrocytes is unclear. Moreover, PK11195 may lack sufficient sensitivity for detecting mild neuroinflammation. We hypothesized that N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl) acetamide (DAA1106), a new ligand that binds specifically to peripheral benzodiazepine receptor, binds to activated microglia in human neurological diseases with higher affinity than does PK11195. We therefore compared the pharmacological binding properties of [3H](R)-PK11195 and [3H]DAA1106 in postmortem tissues from patients with cerebral infarcts, amyotrophic lateral sclerosis, Alzheimer disease, frontotemporal dementia, and multiple sclerosis (n=10 each). In all diseases, [3H]DAA1106 showed a higher binding affinity as reflected by lower dissociation constant (KD) values than that of [3H](R)-PK11195. Moreover, specific binding of both ligands correlated with the presence of activated microglia identified by immunohistochemistry in situ. We conclude that 1) ligands that bind peripheral benzodiazepine receptor mainly label activated microglia in human neurological disorders and that 2) DAA1106 may possess binding characteristics superior to those of PK11195, which may be beneficial for in vivo positron emission tomography imaging.","Acetamides/ pharmacokinetics;Aged;Aged, 80 and over;Autoradiography;Brain/pathology;Female;Humans;Inflammation/pathology/radionuclide imaging;Isoquinolines/pharmacokinetics;Male;Microglia/ metabolism/ radionuclide imaging;Middle Aged;Nervous System Diseases/ metabolism/ radionuclide imaging;Phenyl Ethers/ pharmacokinetics;Positron-Emission Tomography;Radiopharmaceuticals/ pharmacokinetics","Venneti, S.;Wang, G.;Nguyen, J.;Wiley, C. A.",2008,Oct,10.1097/NEN.0b013e318188b204,0,
577,Effects of cholinesterase inhibition on brain white matter volume in Alzheimer's disease,"Brain white matter volume changes were quantified by using voxel-based morphometry in 26 minimal-to-mild Alzheimer's disease patients receiving cholinesterase inhibitors over 20 weeks. Patients treated with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, did not show those reductions in white matter volume that were observed in patients treated with acetylcholinesterase-selective agents, donepezil and galantamine. This is the first time that dual cholinesterase inhibition has been shown to influence white matter volume specifically. The findings are consistent with a thesis that dual cholinesterase inhibition may have neuroprotective potential. Attenuated loss of brain volumes and delayed/slower long-term clinical decline in patients treated with agents such as rivastigmine may be due to less extensive white matter damage and loss of corticosubcortical connectivity.","Acetylcholinesterase/drug effects/metabolism;Aged;Aged, 80 and over;Alzheimer Disease/*drug therapy/enzymology/*pathology;Brain/*drug effects/enzymology/*pathology;Brain Mapping;Cholinesterase Inhibitors/*pharmacology;Cytoprotection/drug effects/physiology;Disease Progression;Drug Synergism;Drug Therapy, Combination;Female;Galantamine/pharmacology;Humans;Image Processing, Computer-Assisted;Indans/pharmacology;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/drug effects/metabolism/pathology;Neural Pathways/drug effects/enzymology/pathology;Neuroprotective Agents/*pharmacology;Phenylcarbamates/pharmacology;Piperidines/pharmacology;Rivastigmine;Treatment Outcome","Venneri, A.;Lane, R.",2009,Feb 18,,0,
578,Cognitive reserve and Alzheimer's disease biomarkers are independent determinants of cognition,"The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-beta load via cerebral spinal fluid amyloid-beta1-42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer's disease, from the Alzheimer's Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer's disease in a group labelled 'cognitively impaired' subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer's disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer's Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory-Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-beta1-42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer's disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-beta1-42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer's disease pathology.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/ complications/metabolism/psychology;Biomass;Cognition Disorders/cerebrospinal fluid/ etiology/psychology;Cognitive Reserve/ physiology;Female;Humans;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Reading;Statistics as Topic;Verbal Learning/physiology","Vemuri, P.;Weigand, S. D.;Przybelski, S. A.;Knopman, D. S.;Smith, G. E.;Trojanowski, J. Q.;Shaw, L. M.;Decarli, C. S.;Carmichael, O.;Bernstein, M. A.;Aisen, P. S.;Weiner, M.;Petersen, R. C.;Jack, C. R., Jr.",2011,May,10.1093/brain/awr049,0,
579,Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly,"Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-beta load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-beta load of >/=1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load >/=1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/complications;Amyloid beta-Peptides/ metabolism;Analysis of Variance;Aniline Compounds;Cerebrovascular Disorders/complications;Cognition Disorders/ pathology/radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Positron-Emission Tomography;Predictive Value of Tests;Thiazoles;Tomography Scanners, X-Ray Computed","Vemuri, P.;Lesnick, T. G.;Przybelski, S. A.;Knopman, D. S.;Preboske, G. M.;Kantarci, K.;Raman, M. R.;Machulda, M. M.;Mielke, M. M.;Lowe, V. J.;Senjem, M. L.;Gunter, J. L.;Rocca, W. A.;Roberts, R. O.;Petersen, R. C.;Jack, C. R., Jr.",2015,Mar,10.1093/brain/awu393,0,
580,Focal epilepsy as first symptom in CADASIL,"Recurrent transient ischemic attacks, migraine and dementia represent the principal symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). During the course of the disease, about 10% of patients may experience epileptic seizures, mainly related to the presence of an ischemic stroke. We present a 30-year-old woman with new-onset focal epilepsy leading to the diagnosis of CADASIL. The neuropsychological testing revealed no cognitive impairment. Interictal EEG demonstrated spikes and polyspikes with low amplitude over the right occipital region during NREM sleep. MRI showed white-matter hyperintensities on both hemispheres with confluent lesions at the right parieto-occipital junction, with juxtacortical components. Like in multiple sclerosis, we can suppose that this type of white matter lesions, close to the cortex, may be causative of seizures. © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.",etiracetam;adult;amplitude modulation;article;asthenia;brain cortex;brain radiography;CADASIL;case report;electroencephalogram;female;focal epilepsy;headache;human;left hemisphere;multiple sclerosis;neuropsychology;nonREM sleep;nuclear magnetic resonance imaging;occipital cortex;parieto-occipital sulcus;priority journal;right hemisphere;spike;treatment duration;white matter,"Velizarova, R.;Mourand, I.;Serafini, A.;Crespel, A.;Gelisse, P.",2011,,,0,
581,Expression of neurofilament proteins in the rat cerebellar cortex as a function of age: an immunohistochemical study,"The present study was designed to assess changes in the expression of cytoskeletal proteins in the cerebellar cortex of rats of different ages using immunohistochemical techniques associated with image analysis. Male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old) were used. Neuronal cytoskeleton was investigated using monoclonal antibodies to phosphorylated neurofilament (NF) proteins of high (H), medium (M) and low+H+M molecular weight (NF triplet). In young and adult rats in which the expression of phosphorylated NF immunostaining was similar, a dark-brown immunoreactivity was observed primarily in axons of the white matter and of basket neurons which surround Purkinje neurons and enter in the molecular layer. In adult rats a NF-H immunoreactivity was sometimes observed within the dendritic tree of Purkinje neurons. A significant decrease in the density of NF immunoreactivity involving the three different subunits investigated was found in the cerebellar cortex of old rats. This suggests that cytoskeletal abnormalities occur not only in senile dementia, but also in the so called 'physiological aging'. The cerebellar cortex may represent an interesting model for evaluating age-dependent changes of cytoskeleton.","Aging/ metabolism;Animals;Cerebellar Cortex/ chemistry;Image Processing, Computer-Assisted;Immunoenzyme Techniques;Male;Neurofilament Proteins/ analysis;Phosphorylation;Rats;Rats, Wistar","Vega, J. A.;Del Valle, M.;Amenta, F.",1994,Jan,,0,
582,[CADASIL: a case series of 11 patients] CADASIL: descripcion de una serie de 11 casos clinicos,"INTRODUCTION: The term CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) refers to a hereditary systemic microangiopathy caused by mutations of the NOTCH3 gene located on chromosome 19. It typically presents in young people with migraine attacks and recurrent ischemic strokes, leading to a progressive subcortical cognitive decline over several years. AIM: To describe the symptoms of onset and clinical manifestations in 11 CADASIL patients diagnosed by genetic testing or skin biopsy. PATIENTS AND METHODS: Detailed physical and neurological examinations, vital signs, electrocardiogram, laboratory investigations (including glucose levels, lipid profile, coagulation studies and homocysteine levels, among others), brain MRI, Mini-Mental Test and Trail Making Test A and B were done. In addition, some patients with complaints related to depressive symptoms or impaired cognition received the Montgomery and Asberg Depression Rating Scale and a battery of neuropsychological examinations (the Stroop Color and Word Test and the V-ADAS-cog that includes the Maze Test). RESULTS AND CONCLUSIONS: Our patients presented with a clinical course and a radiological pattern similar to those described previously in the literature. We found a delay in the detection of this pathology and previous diagnostic errors in some patients and their relatives. Multiple sclerosis was the most frequent misdiagnosis. The course of the disease was barely modified by therapeutic interventions introduced to control the progression of the symptoms. Cognitive complaints in patients with advanced stages were common and the executive abilities were found to be impaired in many cases.","0 (NOTCH3 protein, human);0 (Receptor, Notch3);0 (Receptors, Notch);Adult;Aged;CADASIL/diagnosis/genetics/pathology/ physiopathology;Chromosomes, Human, Pair 19;Cognition Disorders/genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Receptor, Notch3;Receptors, Notch/genetics;Retrospective Studies","Vazquez do Campo, R.;Morales-Vidal, S.;Randolph, C.;Chadwick, L.;Biller, J.",2011,Feb 16,,0,
583,[CADASIL: a case series of 11 patients],"INTRODUCTION: The term CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) refers to a hereditary systemic microangiopathy caused by mutations of the NOTCH3 gene located on chromosome 19. It typically presents in young people with migraine attacks and recurrent ischemic strokes, leading to a progressive subcortical cognitive decline over several years. AIM: To describe the symptoms of onset and clinical manifestations in 11 CADASIL patients diagnosed by genetic testing or skin biopsy. PATIENTS AND METHODS: Detailed physical and neurological examinations, vital signs, electrocardiogram, laboratory investigations (including glucose levels, lipid profile, coagulation studies and homocysteine levels, among others), brain MRI, Mini-Mental Test and Trail Making Test A and B were done. In addition, some patients with complaints related to depressive symptoms or impaired cognition received the Montgomery and Asberg Depression Rating Scale and a battery of neuropsychological examinations (the Stroop Color and Word Test and the V-ADAS-cog that includes the Maze Test). RESULTS AND CONCLUSIONS: Our patients presented with a clinical course and a radiological pattern similar to those described previously in the literature. We found a delay in the detection of this pathology and previous diagnostic errors in some patients and their relatives. Multiple sclerosis was the most frequent misdiagnosis. The course of the disease was barely modified by therapeutic interventions introduced to control the progression of the symptoms. Cognitive complaints in patients with advanced stages were common and the executive abilities were found to be impaired in many cases.","Adult;Aged;CADASIL/diagnosis/genetics/pathology/*physiopathology;Chromosomes, Human, Pair 19;Cognition Disorders/genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Receptors, Notch/genetics;Retrospective Studies","Vazquez do Campo, R.;Morales-Vidal, S.;Randolph, C.;Chadwick, L.;Biller, J.",2011,Feb 16,,0,
584,Hyperintensities on MRI: White matter and depression,,death;dementia;depression;disease association;human;letter;neuropsychiatry;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident;white matter,"Vattakatuchery, J. J.;Joy, J.",2010,,,0,
585,Percheron thalamopeduncular syndrome with cervical dystonia: A case report,"Bilateral thalamic infarctions are usually caused by occlusion of the ""Artery of Percheron"" (AoP). Thalamopeduncular syndrome is among the most common presentations of AoP occlusion. A 59-year-old male presented abrupt decreased level of consciousness. After several weeks, on regaining consciousness, he exhibited oculomotor abnormalities, ataxic gait, cervical dystonia, and cognitive and behavioral changes. Magnetic resonance imaging disclosed thalamic, subthalamic, mammillary and midbrain infarction. Clinical features suggestive of bilateral thalamopeduncular syndrome were identified. Besides the presence of cognitive impairment and behavioral symptoms, cervical dystonia was evident, possibly resulting from interruption of the interconnections among basal ganglia, thalamus, subthalamus, midbrain and cerebellum.",artery of Percheron;cervical dystonia;thalamopeduncular syndrome;torticollis;vascular dementia,"Vasconcellos, L. F.;Tiel, C.;Sudo, F. K.;Moreira, D. M.;Engelhardt, E.",2016,Oct-Dec,,0,
586,"Diagnostic value of high signal abnormalities on T2 weighted MRI in the differentiation of Alzheimer's, frontotemporal and vascular dementias","OBJECTIVE: The occurrence of high signal abnormalities on T2 weighted images is strongly age related. The diagnostic value of these changes in a younger population with dementia is not currently known. We studied the potential of high signal changes on magnetic resonance imaging (MRI) in differentiating Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) in younger patients. METHODS: High signal abnormalities were rated, using a previously validated scale, from hard copies of T2 weighted axial images of 102 patients with AD (n=49), VaD (n=31), FTD (n=22) (mean ages 63-65 years). RESULTS: High signal abnormalities were widespread across AD, VaD and FTD. Although they were most frequent and most severe in the VaD group only lacunes and grade III deep white matter hyperintensities (DWMH) were specific for these patients. CONCLUSIONS: High signal changes on T2 weighted images on MRI are common across degenerative (AD and FTD) and vascular dementias. Although lacunes and grade III DWMH are specific for VaD, the low sensitivities (sensitivities: for lacunes, 0.32; for grade III DWMH, 0.16) limit their use as diagnostic markers for VaD. High signal changes on MRI should be interpreted with caution in dementias. Their presence, even in younger patients, should not deter one from diagnosing AD or FTD.","Aged;Alzheimer Disease/ diagnosis;Basal Ganglia/pathology;Dementia, Vascular/ diagnosis;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Severity of Illness Index;Temporal Lobe/ pathology","Varma, A. R.;Laitt, R.;Lloyd, J. J.;Carson, K. J.;Snowden, J. S.;Neary, D.;Jackson, A.",2002,May,,0,
587,Magnetic resonance imaging of metabolic diseases of the cerebral white matter,"Metabolic diseases of the brain are a rare occurrence. They may be either occurring as inherited diseases causing a destruction of myelin, or they may be the result of toxicity. Neuroimaging, especially magnetic resonance imaging, plays an important role in the detection and classification of these rare diseases. Magnetic resonance spectroscopy is an important tool in the characterization and diagnosis of inherited metabolic diseases. Copyright © 2010 by Lippincott Williams & Wilkins.",,"Vargas, M. I.;Merlini, L.;Haller, S.;Cuvinciuc, V.;Schroth, G.;Pereira, V. M.;Lövblad, K. O.",2009,December,,0,
588,Assessment of cognitive impairment: the role of CT,"The value of CT as a routine screening procedure in the investigation of cognitive impairment is being increasingly challenged. To address this issue, we reviewed the records of 175 patients with intellectual deficits admitted to a Behavioural Neurology Unit over a two-year period. In the vast majority of cases, ie. 82%, the CT served essentially to confirm the clinical impression and added no new diagnostic information that impacted the management of the presenting problem. In 15% of cases the CT scan was helpful for diagnosis, especially in the differentiation between Alzheimer's disease and multi-infarct dementia.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/radiography;Cognition Disorders/*radiography;Dementia, Multi-Infarct/radiography;Female;Humans;Male;Middle Aged;*Tomography, X-Ray Computed","Varga, M.;Wortzman, G.;Freedman, M.",1991,May,,0,
589,MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 1: Postmortem MRI with histopathologic correlation,"The purpose of this study was to correlate postmortem magnetic resonance imaging (MRI) with histopathologic findings in brains of a series of autopsied patients with infantile neuronal ceroid-lipofuscinosis, a recessively inherited progressive encephalopathy. Eight formalin-fixed brains (age range at death, 7 to 13 years) were examined with MRI. One patient had also undergone brain MRI2 years before death. Histopathologic analyses were made from standard areas selected on the basis of the MRI scans. Postmortem MRI findings did not differ significantly from the findings in the patient who was also examined during life. Typical findings were extreme cerebral atrophy and hypointensity of the gray-matter structures in relation to the white matter on T(2)-weighted images, a pattern the reverse of normal. Characteristic histologic findings were almost complete loss of cortical neurons and secondary loss of axons and myelin sheaths in the white matter. The drastically altered relative intensities of the gray- and white-matter structures on the MRI scans reflected replacement of the neurons with hypertrophic astrocytes and/or macrophages filled with storage material.",,"Vanhanen, S. L.;Raininko, R.;Santavuori, P.;Autti, T.;Haltia, M.",1995,1995,,0,
590,"Early differential diagnosis of infantile neuronal ceroid lipofuscinosis, Rett syndrome, and Krabbe disease by CT and MR","PURPOSE: To compare early radiologic findings in three clinically similar progressive encephalopathies of childhood. METHODS: Brain CT and/or MR studies were done in 57 children 3 to 36 months of age: 16 with infantile neuronal ceroid lipofuscinosis, 5 with Rett syndrome, 6 with Krabbe disease, and 30 control subjects with normal neurologic status. In addition, previous descriptions in the literature were collected. RESULTS: No significant changes were seen in Rett syndrome. Early atrophy was found in infantile neuronal ceroid lipofuscinosis and in Krabbe disease, being more severe in the latter. The thalami were hyperdense in 4 of 13 patients with infantile neuronal ceroid lipofuscinosis and in 1 of 4 patients with Krabbe disease (in the literature in 12 of 30 examinations). Cerebral calcifications and density abnormalities in the cerebral and cerebellar white matter were seen in Krabbe disease only. On MR, the white matter changes in the two diseases were differently located. In every patient with infantile neuronal ceroid lipofuscinosis, decreased T2 signal was seen in the thalami and periventricular high-signal rims after the age of 13 months. Hypointensity of the thalami and basal ganglia was seen in both diseases, but Krabbe disease showed more variations. Abnormalities of cerebellar intensity were found in Krabbe disease only. CONCLUSIONS: CT and MR are of value in the differential diagnosis of these three diseases. MR especially facilitates the early diagnosis of infantile neuronal ceroid lipofuscinosis.",article;brain disease;childhood disease;clinical article;computer assisted tomography;controlled study;diagnostic value;differential diagnosis;globoid cell leukodystrophy;human;infant;lipofuscinosis;nuclear magnetic resonance imaging;preschool child;Rett syndrome,"Vanhanen, S. L.;Raininko, R.;Santavuori, P.",1994,,,0,
591,MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 2: MRI findings in 21 patients,"The purpose of this study was to demonstrate the course of infantile neuronal ceroid-lipofuscinosis with brain magnetic resonance imaging (MRI) in children aged 3 months to 11 years. Twenty-one patients and 46 neurologically normal controls of the same age were examined. The images were evaluated visually; then signal intensities were measured and related to those of references. MRI abnormalities were detectable before clinical symptoms. The radiologic picture of the brain varied with the duration of the disease. Pathognomonic MRI findings in the early stage of the disease were generalized cerebral atrophy, strong thalamic hypointensity to the white matter and to the basal ganglia, and thin periventricular high-signal rims from 13 months onward on T(2)-weighted images. In patients over 4 years old, cerebral atrophy was extreme, and the signal intensity of the entire white matter was higher than that of the gray matter, which is the reverse of normal. This study showed that the abnormalities seen on MRI progress rapidly during the first 4 years of life, then stabilize, in conformity with the clinical and histopathologic pictures of infantile neuronal ceroid-lipofuscinosis.",,"Vanhanen, S. L.;Raininko, R.;Autti, T.;Santavuori, P.",1995,1995,,0,
592,High resolution imaging of cerebral small vessel disease with 7 T MRI,"Small vessel disease (SVD) refers to all pathological processes that affect the small vessels of the brain. SVD is an important cause of acute stroke, but is also a leading cause of aging-related cognitive decline and dementia, due to more insidious brain parenchymal damage. The introduction of high field strength MRI (7 T) is likely to offer important new perspectives on the role of SVD in these disorders. In this overview we illustrate the opportunities that 7 T MRI offers in high resolution vascular imaging. In particular, we will show the capability of 7 T MRI to depict the small arteries and veins in the brain, the vascular wall of intracranial arteries, perivascular spaces, and microvascular parenchymal lesions, including microbleeds and microinfarcts.",,"van Veluw, S. J.;Zwanenburg, J. J.;Hendrikse, J.;van der Kolk, A. G.;Luijten, P. R.;Biessels, G. J.",2014,,10.1007/978-3-319-02411-0_21,0,
593,Cortical microinfarcts on 3T MRI: Clinical correlates in memory-clinic patients,"INTRODUCTION: This is the first study to assess cerebral microinfarcts (CMIs) on 3 tesla (3T) magnetic resonance imaging (MRI) in a memory clinic population. METHODS: We included 238 consecutive patients (aged 72.5 +/- 9.1 years) from a memory clinic in Singapore. All patients underwent extensive neurological and neuropsychological testing and 3T MRI on the same day. Cortical CMI rating criteria were adapted from a previous study on 7T MRI. We analyzed the frequency and association of cortical CMIs with demographic, clinical, cognition, and other MRI findings. RESULTS: Seventy-five patients (32%) had cortical CMIs (median 1, range 1-43). Patients with CMIs showed worse cognitive functioning on MMSE, and in the domains of language and visuoconstruction. The presence of CMIs was related to other markers of small vessel disease, but most strongly larger cortical infarcts. Patients with CMIs were more often diagnosed with vascular dementia. DISCUSSION: Cortical CMIs on 3T MRI are a novel marker of cerebrovascular disease in dementia.",,"van Veluw, S. J.;Hilal, S.;Kuijf, H. J.;Ikram, M. K.;Xin, X.;Yeow, T. B.;Venketasubramanian, N.;Biessels, G. J.;Chen, C.",2015,Dec,10.1016/j.jalz.2014.12.010,0,
594,Cerebral cortical microinfarcts at 7Tesla MRI in patients with early Alzheimer's disease,"Cerebral microinfarcts (CMIs) are a common finding in neuropathological studies of aging and dementia. Recently, it has become possible to detect CMIs in vivo. We studied CMI occurrence in 29 patients with mild cognitive impairment or early Alzheimer's disease (AD) and 22 non-demented individuals on 7Tesla MRI. CMI occurrence in patients (55%) and controls (45%) was not significantly different. In patients, CMI number tended to be related to microbleed number (p = 0.07). This first in vivo study of CMIs in early AD does not confirm findings from autopsy studies. Further studies are needed to clarify the role of CMIs in AD.",Aged;Alzheimer Disease/diagnosis/ etiology;Autopsy;Cerebral Infarction/ complications/ diagnosis;Cognition Disorders/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ etiology;Reference Values,"van Veluw, S. J.;Heringa, S. M.;Kuijf, H. J.;Koek, H. L.;Luijten, P. R.;Biessels, G. J.",2014,,10.3233/jad-131040,0,
595,Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images,"Cerebral microinfarcts are frequent findings in the post-mortem human brain, and are related to cognitive decline and dementia. Due to their small sizes it is challenging to study them on clinical MRI scans. It was recently demonstrated that cortical microinfarcts can be depicted with MRI scanners using high magnetic field strengths (7T). Based on this experience, a proportion of these lesions is also visible on lower resolution 3T MRI. These findings were corroborated with ex vivo imaging of post-mortem human brain tissue, accompanied by histopathological verification of possible cortical microinfarcts. Here an ex vivo imaging protocol is presented, for the purpose of validating MR observed cerebral microvascular pathology with histological evaluation. Furthermore, guidelines are provided for the assessment of cortical microinfarcts on both in vivo 7T and 3T MR images. These guidelines provide researchers with a tool to rate cortical microinfarcts on in vivo images of larger patient samples, to further unravel their clinical relevance in cognitive decline and dementia, and establish these lesions as a novel biomarker of cerebral small vessel disease.",,"van Veluw, S. J.;Biessels, G. J.;Luijten, P. R.;Zwanenburg, J. J.",2015,,10.3791/53125,0,
596,Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy,"OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. METHODS: Five decedents (mean age at death 79.6 +/- 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury. RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury. CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.",,"van Veluw, S. J.;Biessels, G. J.;Klijn, C. J.;Rozemuller, A. J.",2016,Mar 1,10.1212/wnl.0000000000002419,0,
597,Baseline white matter microstructural integrity is not related to cognitive decline after 5years: The RUN DMC study,"Objectives: Traditional markers of cerebral small vessel disease (SVD) are related to cognition and cognitive decline, but this relation isweak. Therefore other factors may determine the transition from intact cognitive performance to cognitive decline, such as the damage of the cerebralwhite matter at the microstructural level. Little is known about the association between microstructural integrity of thewhite matter and changes in cognition. In this study we investigated the relation between baseline microstructural integrity and change in cognitive function. Methods: 503 participants of the RUN DMC study with SVD without dementia, 398 of whom (79.1%) underwent repeated cognitive testing at follow-up, with amean follow-up time of 5.4 years (± SD 0.2), and among others FLAIR MRI and diffusion tensor imaging (DTI). At baseline Mean Diffusivity (MD) and mean Fractional Anisotropy (FA) were measured in both whitematter hyperintensities (WMH) and normal appearing white matter (NAWM). A linear regression analysiswas performed assessing the association between baseline diffusion parameters and decline in cognitive domains. Results: An inverse association was found between baselineMD in the NAWMand decline in Cognitive Index (ß= 0.17; p = 0.035), adjusted for age, sex, education, presence of depressive symptoms at baseline, normalized TBV, lacunes andWMH volume. However, no significant associations were found between diffusion parameters and decline in any cognitive domain after Bonferroni correction. Conclusions: In contrast to cross-sectional studies, in older adults with SVD microstructural integrity of the white matter as assessed with DTI is not related to decline in global cognitive function or any other subdomain.",,"van Uden, I. W. M.;van der Holst, H. M.;Schaapsmeerders, P.;Tuladhar, A. M.;van Norden, A. G. W.;de Laat, K. F.;Norris, D. G.;Claassen, J. A. H. R.;van Dijk, E. J.;Richard, E.;Kessels, R. P. C.;de Leeuw, F. E.",2015,1,,0,
598,White matter integrity and depressive symptoms in cerebral small vessel disease: The RUN DMC study,"Objective Depressive symptoms are common in elderly with cerebral small vessel disease (SVD). As not every individual with SVD experiences depressive symptoms, other factors might play a role. We therefore investigated the white matter (WM) integrity of the white matter tracts in elderly with depressive symptoms, independent of global cognitive function, by applying the tract-based spatial statistics (TBSS). Design Prospective cohort study with cross-sectional baseline data. Setting Radboud University Nijmegen Medical Centre, The Netherlands. Participants 438 individuals aged between 50-85 years, with SVD without dementia. Measurements Diffusion tensor imaging parameters and depressive symptoms, assessed with the Center for Epidemiologic Studies Depression Scale. Results Compared with non-depressed participants (N = 287), those with depressive symptoms (N = 151) had lower fractional anisotropy in the genu and body of the corpus callosum, bilateral inferior fronto-occipital fasciculus, uncinate fasciculus, and corona radiata. These differences disappeared after adjustment for white matter hyperintensities (WMH) and lacunar infarcts. Mean-, axial-and radial diffusivity were higher in these areas in participants with depressive symptoms. After additional adjustment for WMH and lacunar infarcts, the changes observed in radial diffusivity also disappeared. Adding global cognition as confounding variable altered the diffusion parameters only slightly. Conclusion This study indicates that elderly with depressive symptoms show a lower WM integrity, independent of global cognitive function, and that the presence of SVD is mostly responsible, affecting the fronto-subcortical regions and hereby disrupting the neural circuitry involved in mood regulation.",,"Van Uden, I. W. M.;Tuladhar, A. M.;De Laat, K. F.;Van Norden, A. G. W.;Norris, D. G.;Van Dijk, E. J.;Tendolkar, I.;De Leeuw, F. E.",2015,1,,0,
599,Late-onset depressive symptoms increase the risk of dementia in small vessel disease,"OBJECTIVE: We prospectively investigated the role of depressive symptoms (DS) on all-cause dementia in a population with small vessel disease (SVD), considering onset age of DS and cognitive performance. METHODS: The RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort) is a prospective cohort study among 503 older adults with SVD on MRI without dementia at baseline (2006), with a follow-up of 5 years (2012). Kaplan-Meier curves stratified for DS and dementia risk were compared using log-rank test. We calculated hazard ratios using Cox regression analyses. RESULTS: Follow-up was available for 496 participants (mean baseline age 65.6 years [SD 8.8]; mean follow-up time 5.2 years). All-cause dementia developed in 41 participants. The 5.5-year dementia risk was higher in those with DS (hazard ratio 2.7, 95% confidence interval 1.4-5.2), independent of confounders. This was driven by those with late-onset DS. Five-year cumulative risk difference for dementia was higher in participants with depressive symptoms who had high baseline cognitive performance (no DS 0.0% vs DS 6.9%, log-rank p < 0.001) compared with those who had low cognitive performance at baseline. CONCLUSIONS: Late-onset DS increases dementia risk, independent of SVD. Especially in those with relatively high cognitive performance, DS indicate a higher risk. In contrast to current practice, clinicians should monitor those with DS who also show relatively good cognitive test scores.",,"van Uden, I. W.;van der Holst, H. M.;van Leijsen, E. M.;Tuladhar, A. M.;van Norden, A. G.;de Laat, K. F.;Claassen, J. A.;van Dijk, E. J.;Kessels, R. P.;Richard, E.;Tendolkar, I.;de Leeuw, F. E.",2016,Sep 13,10.1212/wnl.0000000000003089,0,
600,White Matter and Hippocampal Volume Predict the Risk of Dementia in Patients with Cerebral Small Vessel Disease: The RUN DMC Study,"BACKGROUND: The relationship between cerebral small vessel disease (SVD) and dementia has been studied without considering white matter (WM) volume, the microstructural integrity of the WM surrounding the SVD, and grey matter (GM). OBJECTIVE: We prospectively investigated the relationship between these structures and the risk of dementia, and formed a prediction model to investigate which characteristics (macro- or microstructural) explained most of the variance. METHODS: The RUN DMC study is a prospective cohort study among 503 non-demented participants with an age between 50 and 85 years at baseline, with baseline assessment in 2006 and follow-up assessment in 2012. Two were lost to follow-up (yielding a 99.6% response-rate). Cox regression analysis was used, to calculate hazard ratios for dementia, of baseline MRI characteristics. Tract-Based Spatial Statistics (TBSS) analysis was used to assess the added value of microstructural integrity of the WM. RESULTS: Mean age at baseline was 65.6 years (SD 8.8) and 56.8% was male. 43 participants developed dementia (8.6% ), resulting in a 5.5-year cumulative risk of 11.1% (95% CI 7.7-14.6). Low WM and hippocampal volume are significant predictors for dementia. WM, WM hyperintensities, and hippocampal volume explained most of the variance. TBSS analyses showed no additional value of diffusion parameters. CONCLUSIONS: WM and hippocampal volume were the main predictors for the development of incident dementia at 5-year follow-up in elderly with SVD. There was no additional diagnostic value of the diffusion tensor imaging parameters on top of the macrostructural characteristics.",,"van Uden, I. W.;van der Holst, H. M.;Tuladhar, A. M.;van Norden, A. G.;de Laat, K. F.;Rutten-Jacobs, L. C.;Norris, D. G.;Claassen, J. A.;van Dijk, E. J.;Kessels, R. P.;de Leeuw, F. E.",2015,Nov 2,10.3233/jad-150573,0,
601,Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study,"INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume. Hum Brain Mapp 37:327-337, 2016. (c) 2015 Wiley Periodicals, Inc.",,"van Uden, I. W.;Tuladhar, A. M.;van der Holst, H. M.;van Leijsen, E. M.;van Norden, A. G.;de Laat, K. F.;Rutten-Jacobs, L. C.;Norris, D. G.;Claassen, J. A.;van Dijk, E. J.;Kessels, R. P.;de Leeuw, F. E.",2016,Jan,10.1002/hbm.23029,0,
602,Hypertension in the elderly is associated with white matter lesions and cognitive decline,"Forty-two elderly patients (mean age, 66.2 ± 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 ± 4.8 yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2-weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi-square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini-Mental State Examination, the Stroop color-word test, Trailmaking test, and the visual subtest of the Wechsler Memory Scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long-standing hypertension in some patients may cause not only strokes but also chronic end-organ damage of the brain in the form of demyelination of the white matter, with cognitive decline.",,"Van Swieten, J. C.;Geyskes, G. G.;Derix, M. M. A.;Peeck, B. M.;Ramos, L. M. P.;Van Latum, J. C.;Van Gijn, J.",1991,1991,,0,
603,Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study,"BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.","Brain/blood supply;Dementia, Vascular/*diagnosis/*epidemiology;Humans;Magnetic Resonance Imaging/standards/*statistics & numerical data;Netherlands/epidemiology;Observer Variation;Reproducibility of Results","van Straaten, E. C.;Scheltens, P.;Knol, D. L.;van Buchem, M. A.;van Dijk, E. J.;Hofman, P. A.;Karas, G.;Kjartansson, O.;de Leeuw, F. E.;Prins, N. D.;Schmidt, R.;Visser, M. C.;Weinstein, H. C.;Barkhof, F.",2003,Aug,10.1161/01.str.0000083050.44441.10,0,
604,Disturbed phase relations in white matter hyperintensity based vascular dementia: an EEG directed connectivity study,"OBJECTIVE: White matter hyperintensities (WMH), a feature seen on magnetic resonance imaging (MRI) and regarded to reflect small vessel disease, can lead to vascular dementia (WMH-VaD). In WMH-VaD, cognitive deficits typically consist of executive function disturbances, and reduced information processing speed, regarded as a result of cerebral hypoperfusion. We aimed to investigate whether this patient group has typical functional differences from controls. METHODS: Resting-state encephalography studies of 17 VaD patients and 17 age- and gender matched non-demented controls were analysed in the delta, theta, alpha1 and 2, and beta frequency bands. Undirected functional connectivity between electrodes was established with the Phase Lag Index (PLI) and directed functional connectivity with the directed Phase Lag Index (dPLI). PLI and dPLI were related to performance in cognitive testing. RESULTS: Mean PLI did not differ between patients and controls. In the control group dPLI showed anterior to posterior phase gradients in all bands except the delta band. In the VaD patient group this pattern was significantly different without a clear directional pattern. No relationship with cognition was demonstrated. CONCLUSIONS: This study shows a clear front-to-back direction of connectivity in non-demented controls. In VaD patients with extensive WMH, this pattern is disturbed. SIGNIFICANCE: Structural damage at the regions of long distance white matter tracts may induce changes in the direction of phase relationships of distinct brain regions.","Aged;Aged, 80 and over;Brain/pathology/ physiopathology;Cognition;Dementia, Vascular/pathology/ physiopathology;Electroencephalography;Female;Humans;Magnetic Resonance Imaging/methods;Male;Nerve Net/pathology/ physiopathology;Neural Pathways/pathology/physiopathology;White Matter/pathology/ physiopathology","van Straaten, E. C.;den Haan, J.;de Waal, H.;van der Flier, W. M.;Barkhof, F.;Prins, N. D.;Stam, C. J.",2015,Mar,10.1016/j.clinph.2014.05.018,0,
605,Cerebral Small Vessel Disease and Association With Higher Incidence of Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik Study,"OBJECTIVE: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) leads to depressive symptoms by disruption of brain structures involved in mood regulation. However, longitudinal data on the association between CSVD and depressive symptoms are scarce. The authors investigated the association between CSVD and incident depressive symptoms. METHOD: Longitudinal data were taken from the Age, Gene/Environment Susceptibility-Reykjavik Study of 1,949 participants free of dementia and without baseline depressive symptoms (mean age: 74.6 years [SD=4.6]; women, 56.6%). MRI markers of CSVD, detected at baseline (2002-2006) and follow-up (2007-2011), included white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces, and total brain parenchyma volume. Incident depressive symptoms were defined by a score >/=6 on the 15-item Geriatric Depression Scale and/or use of antidepressant medication. RESULTS: Depressive symptoms occurred in 10.1% of the participants. The association for a greater onset of depressive symptoms was significant for participants with 1 standard deviation increase in white matter hyperintensity volume over time, new subcortical infarcts, new Virchow-Robin spaces, 1 standard deviation lower total brain volume at baseline, and 1 standard deviation decreased total brain volume over time, after adjustments for cognitive function and sociodemographic and cardiovascular factors. Results were qualitatively similar when change in the Geriatric Depression Scale score over time was used as the outcome instead of incident depressive symptoms. CONCLUSIONS: Most markers of progression of CSVD over time and some markers of baseline CSVD are associated with concurrently developing new depressive symptoms. These findings support the vascular depression hypothesis.","Aged;Aged, 80 and over;Brain/pathology;Cerebral Infarction/diagnosis/epidemiology/psychology;Cerebral Small Vessel Diseases/*diagnosis/*epidemiology/genetics/psychology;Cohort Studies;Depressive Disorder/*diagnosis/*epidemiology/genetics/psychology;Female;Gene-Environment Interaction;Genetic Predisposition to Disease;Humans;Incidence;Longitudinal Studies;Magnetic Resonance Imaging;Male;Netherlands;Statistics as Topic","van Sloten, T. T.;Sigurdsson, S.;van Buchem, M. A.;Phillips, C. L.;Jonsson, P. V.;Ding, J.;Schram, M. T.;Harris, T. B.;Gudnason, V.;Launer, L. J.",2015,Jun,10.1176/appi.ajp.2014.14050578,0,
606,Glucocorticoid receptor variant and risk of dementia and white matter lesions,"OBJECTIVE: Elevated glucocorticoid levels are associated with dementia. A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities. METHODS: This study was performed in two prospective population-based cohort studies among elderly. The first study included 6034 participants who were screened for dementia (mean follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI at baseline and follow-up. The ER22/23EK allele was assessed for association with dementia, cognitive function and white matter lesions. RESULTS: The ER22/23EK allele was associated with a decreased risk of dementia. Among non-demented participants, ER22/23EK-carriers had a better performance on psychomotor speed tests than non-carriers. No differences were found in memory function between genotypes. In addition, both presence and progression of white matter lesions was lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI. CONCLUSIONS: Our findings suggest a protective effect of the ER22/23EK allele on the risk of dementia and white matter lesions.","Aged;Aged, 80 and over;Comorbidity;Dementia/diagnosis/*epidemiology/*genetics;Demyelinating Diseases/diagnosis/*epidemiology/*genetics;Female;Genetic Variation/genetics;Humans;Magnetic Resonance Imaging/*statistics & numerical data;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Netherlands/epidemiology;Polymorphism, Single Nucleotide/genetics;Prevalence;Receptors, Glucocorticoid/*genetics;Risk Assessment/methods;Risk Factors","van Rossum, E. F.;de Jong, F. J.;Koper, J. W.;Uitterlinden, A. G.;Prins, N. D.;van Dijk, E. J.;Koudstaal, P. J.;Hofman, A.;de Jong, F. H.;Lamberts, S. W.;Breteler, M. M.",2008,May,10.1016/j.neurobiolaging.2006.11.016,0,
607,"Cohort study ON Neuroimaging, Etiology and Cognitive consequences of Transient neurological attacks (CONNECT): study rationale and protocol","BACKGROUND: Transient ischemic attacks (TIA) are characterized by acute onset focal neurological symptoms and complete recovery within 24 hours. Attacks of nonfocal symptoms not fulfilling the criteria for TIA but lacking a clear alternative diagnosis are called transient neurological attacks (TNA). Although TIA symptoms are transient in nature, cognitive complaints may persist. In particular, attacks consisting of both focal and nonfocal symptoms (mixed TNA) have been found to be associated with an increased risk of dementia. We aim to study the prevalence, etiology and risk factors of cognitive impairment after TIA or TNA. METHODS/DESIGN: CONNECT is a prospective cohort study on cognitive function after TIA and TNA. In total, 150 patients aged >/=45 years with a recent (<7 days after onset) TIA or TNA and no history of stroke or dementia will be included. We will classify events as: TIA, nonfocal TNA, or mixed TNA. Known short lasting paroxysmal neurological disorders like migraine aura, seizures and Meniere disease are excluded from the diagnosis of TNA. Patients will complete a comprehensive neuropsychological assessment and undergo MRI <7 days after the qualifying event and again after six months. The primary clinical outcomes will be cognitive function at baseline and six months after the primary event. Imaging outcomes include the prevalence and evolution of DWI lesions, white matter hyperintensities and lacunes, as well as resting state networks functionality and white matter microstructural integrity. Differences between types of event and DWI, as well as determinants of both clinical and imaging outcomes, will be assessed. DISCUSSION: CONNECT can provide insight in the prevalence, etiology and risk factors of cognitive impairment after TIA and TNA and thereby potentially identify a new group of patients at increased risk of cognitive impairment.","Aged;Cognition Disorders/ epidemiology/pathology/psychology;Cohort Studies;Female;Humans;Ischemic Attack, Transient/ epidemiology/pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuroimaging;Neuropsychological Tests;Prevalence;Prospective Studies;Risk Factors","van Rooij, F. G.;Tuladhar, A. M.;Kessels, R. P.;Vermeer, S. E.;Goraj, B. M.;Koudstaal, P. J.;Norris, D. G.;de Leeuw, F. E.;van Dijk, E. J.",2015,,10.1186/s12883-015-0295-3,0,
608,Persistent cognitive impairment after transient ischemic attack,"BACKGROUND AND PURPOSE: By definition, the symptoms of a transient ischemic attack (TIA) subside completely within 24 hours. Imaging studies show signs of persistent ischemic tissue damage in a substantial amount of patients with TIA. Cerebral infarction can cause permanent cognitive impairment. Whether permanent cognitive impairment occurs after TIA is unclear, as is its profile. METHODS: Patients with TIA aged 45 to 65 years without prior stroke or dementia underwent comprehensive neuropsychological testing within 3 months. Z scores per cognitive domain were obtained, based on the mean of a control group within the same age range. Cognitive impairment was defined as a domain z score <-1.65. Patients underwent either computed tomography or MRI brain imaging. RESULTS: One hundred seven patients with TIA (63% women, mean age, 56.6 years) were included and compared with 81 controls (56% women, mean age, 52.9 years). Patients performed worse on all cognitive domains except episodic memory. Working memory (25%), attention (22%), and information processing speed (16%) were most frequently impaired and more often than in the control group (age- and sex-adjusted odds ratios, respectively, 22.5 [95% confidence interval, 2.9-174.3], 6.8 [1.9-24.3], 7.1 [1.5-32.5]). More than 35% of patients with TIA had impairment of >/=1 cognitive domain. Presence of silent brain infarcts was related to worse executive functioning but did not explain the whole relationship between TIA and cognitive impairment. CONCLUSIONS: More than a third of patients with TIA have impairment of >/=1 cognitive domain within 3 months after their TIA. The affected domains fit in the vascular cognitive impairment profile.","Aged;Attention;Brain/ pathology/radiography;Cognition;Cognition Disorders/ etiology/pathology/psychology/radiography;Executive Function;Female;Humans;Ischemic Attack, Transient/ complications/pathology/psychology/radiography;Magnetic Resonance Imaging;Male;Memory, Short-Term;Middle Aged;Neuropsychological Tests","van Rooij, F. G.;Schaapsmeerders, P.;Maaijwee, N. A.;van Duijnhoven, D. A.;de Leeuw, F. E.;Kessels, R. P.;van Dijk, E. J.",2014,Aug,10.1161/strokeaha.114.005205,0,
609,Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging,"PURPOSE: To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND METHODS: The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. RESULTS: Interobserver agreement was excellent for detecting microinfarcts (kappa = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). CONCLUSION: Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Case-Control Studies;Cerebral Infarction/ diagnosis/epidemiology;Cognition Disorders/ pathology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Prevalence","van Rooden, S.;Goos, J. D.;van Opstal, A. M.;Versluis, M. J.;Webb, A. G.;Blauw, G. J.;van der Flier, W. M.;Scheltens, P.;Barkhof, F.;van Buchem, M. A.;van der Grond, J.",2014,Jan,10.1148/radiol.13130743,0,
610,Cognitive function in small vessel disease: the additional value of diffusion tensor imaging to conventional magnetic resonance imaging: the RUN DMC study,"The structural integrity of the cerebral white matter, including that of the white matter lesions (WML) and of the surrounding normal appearing white matter (NAWM), can be assessed with diffusion tensor imaging (DTI), which is suggested to be of added value in the explanation of cognitive dysfunction in cerebral small vessel disease (SVD). We investigated the value of DTI of NAWM and WML in addition to conventional magnetic resonance imaging (MRI) parameters in the variance of cognitive performance in subjects with SVD. 499 individuals with SVD, 50-85 years, without dementia, underwent MRI scanning, including a DTI sequence. Grey matter, white matter (WM), and WML volume, number of microbleeds, lacunar and territorial infracts, and mean diffusivity (MD) and fractional anisotropy (FA) in NAWM, WML, and total WM were related to cognitive performance in multivariate regression analyses, after adjustment for age, gender, and education. All MRI parameters together accounted for 1-6% of the variance in cognitive function on top of 22-36% already explained by age, gender, and level of education. Both mean MD and FA of the NAWM, WML, and total WM did not substantially contribute to the explained variance of cognitive function, to that already explained by conventional MRI parameters. When considered separately, the MD of the (NA)WM had the strongest association with cognitive performance. In conclusion, DTI of NAWM and WML has limited additional value to conventional MRI parameters in the etiological explanation of the variance in cognitive function among individuals with SVD.","Aged;Aged, 80 and over;Cerebral Small Vessel Diseases/ diagnosis/epidemiology/etiology;Cognition/ physiology;Cognition Disorders/ diagnosis/epidemiology/ physiopathology;Cohort Studies;Diffusion Tensor Imaging/methods/ standards;Female;Humans;Magnetic Resonance Imaging/methods/ standards;Male;Middle Aged;Netherlands/epidemiology;Prospective Studies","van Norden, A. G.;van Uden, I. W.;de Laat, K. F.;van Dijk, E. J.;de Leeuw, F. E.",2012,,10.3233/jad-2012-120784,0,
611,Cerebral microbleeds are related to subjective cognitive failures: the RUN DMC study,"Cerebral small vessel disease (SVD), including white matter lesions (WML) and lacunar infarcts, is related to objective cognitive impairment but also to subjective cognitive failures (SCF). SCF have reported to be an early predictor of dementia. Cerebral microbleeds (MB) are another manifestation of SVD and have been related to cognitive impairment, but the role of MB in SCF has never been studied. We therefore investigated whether MB are related to SCF among non-demented elderly individuals with SVD, independent of coexisting WML and lacunar infarcts. The RUN DMC study is a prospective cohort study among 503 older persons with cerebral SVD between 50 and 85 years of age. All participants underwent FLAIR and T2* scanning. SCF, subjective memory failures (SMF), and subjective executive failures (SEF) were assessed. The relation between SCF and the presence, number and location of MB was assessed by linear regression analyses adjusted for age, sex, education, depressive symptoms, cognitive function, total brain volume, normalized hippocampal volume, territorial infarcts, WML, and lacunar infarcts. MB were present in 11%. We found a relation between the presence, total number and lobar located MB, and SCF, SMF, and SEF and the reported progression of these failures, especially in participants with good objective cognitive function. In conclusion, MB are related to SCF independent of co-existing WML and lacunar infarcts, especially in those with good objective cognitive performance. These results suggest that MB are associated with the earliest manifestations of cognitive impairment. MB may help us to understand the role of the ever-expanding spectrum of SVD in cognitive impairment.","Aged;Aged, 80 and over;Aging/*pathology;Brain/*pathology;Cerebral Hemorrhage/*complications/diagnosis/*pathology;Cerebral Small Vessel Diseases/*complications/diagnosis/*pathology;Cognition Disorders/diagnosis/*etiology/*pathology;Cohort Studies;*Diffusion Magnetic Resonance Imaging;Humans;Middle Aged;Prospective Studies;Risk Factors","van Norden, A. G.;van Uden, I. W.;de Laat, K. F.;Gons, R. A.;Kessels, R. P.;van Dijk, E. J.;de Leeuw, F. E.",2013,Sep,10.1016/j.neurobiolaging.2013.03.021,0,
612,Diffusion tensor imaging and cognition in cerebral small vessel disease: the RUN DMC study,"BACKGROUND: Cerebral small vessel disease (SVD) is very common in elderly and related to cognition, although this relation is weak. This might be because the underlying pathology of white matter lesions (WML) is diverse and cannot be properly appreciated with conventional FLAIR MRI. In addition, conventional MRI is not sensitive to early loss of microstructural integrity of the normal appearing white matter (NAWM), which might be an important factor. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity and we have used this to investigate the relation between white matter integrity, in both WML and NAWM, and cognition among elderly with cerebral SVD. METHODS: The RUN DMC study is a prospective cohort study among 503 independently living, non-demented elderly with cerebral SVD aged between 50 and 85 years. All subjects underwent MRI and DTI scanning. WML were segmented manually. We measured mean diffusivity (MD) and fractional anisotropy (FA), as assessed by DTI in both WML and NAWM. RESULTS: Inverse relations were found between MD in the WML and NAWM and global cognitive function (beta=-.11, p<0.05; beta=-.18, p<0.001), psychomotor speed (beta=-.15, p<0.01; beta=-.18, p<0.001), concept shifting (beta=-.11, p<0.05; beta=-.10, p<0.05) and attention (beta=-.12, p<0.05; beta=-.15, p<0.001). The relation between DTI parameters in both WML and NAWM and cognitive performance was most pronounced in subjects with severe WML. CONCLUSION: DTI parameters in both WML and NAWM correlate with cognitive performance, independent of SVD. DTI may be a promising tool in exploring the mechanisms of cognitive decline and could function as a surrogate marker for disease progression in therapeutic trials. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.","Aged;Anisotropy;Brain/ pathology;Cerebral Small Vessel Diseases/ diagnosis/ pathology;Cognition Disorders/ diagnosis/ pathology;Cohort Studies;Diffusion Tensor Imaging/methods;Disease Progression;Female;Humans;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/pathology;Prospective Studies","van Norden, A. G.;de Laat, K. F.;van Dijk, E. J.;van Uden, I. W.;van Oudheusden, L. J.;Gons, R. A.;Norris, D. G.;Zwiers, M. P.;de Leeuw, F. E.",2012,Mar,10.1016/j.bbadis.2011.04.008,0,
613,Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol,"BACKGROUND: Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated. METHODS/DESIGN: The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI. DISCUSSION: The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from ""normal"" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism.","Aged;Aged, 80 and over;Brain/blood supply/ pathology/ physiopathology;Cerebrovascular Disorders/complications/ pathology/ physiopathology;Clinical Protocols;Dementia/complications;Diffusion Tensor Imaging/methods;Disease Progression;Female;Geriatric Assessment/ methods;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Parkinsonian Disorders/complications;Prospective Studies;Risk Factors","van Norden, A. G.;de Laat, K. F.;Gons, R. A.;van Uden, I. W.;van Dijk, E. J.;van Oudheusden, L. J.;Esselink, R. A.;Bloem, B. R.;van Engelen, B. G.;Zwarts, M. J.;Tendolkar, I.;Olde-Rikkert, M. G.;van der Vlugt, M. J.;Zwiers, M. P.;Norris, D. G.;de Leeuw, F. E.",2011,,10.1186/1471-2377-11-29,0,
614,Diffusion tensor imaging of the hippocampus and verbal memory performance: the RUN DMC study,"BACKGROUND: Cerebral small vessel disease (SVD) and hippocampal atrophy are related to verbal memory failures and may ultimately result in Alzheimer's disease. However, verbal memory failures are often present before structural changes on conventional MRI appear. Changes in microstructural integrity of the hippocampus, which cannot be detected with conventional MRI, may be the underlying pathological substrate. With diffusion tensor imaging (DTI), we investigated the relation between the microstructural integrity of the hippocampus and verbal memory performance in 503 nondemented elderly with SVD. METHODS: The Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study is a prospective cohort study among 503 nondemented elderly with cerebral SVD aged between 50 and 85 years. All participants underwent T1 MPRAGE, fluid-attenuated inversion recovery, DTI scanning and the Rey Auditory Verbal Learning Test. After manual segmentation of the hippocampi, we calculated the mean diffusivity (MD) and fractional anisotropy in both hippocampi. The relation between memory performance and hippocampal DTI parameters was adjusted for age, sex, education, depressive symptoms, hippocampal, and white-matter lesions volume and lacunar infarcts. RESULTS: We found inverse relations between hippocampal MD and verbal memory performance (beta = -0.22; P < 0.001), immediate recall (beta = -0.22; P < 0.001), delayed recall (beta = -0.20; P < 0.001), and forgetting rate (beta = -0.13; P = 0.025), most pronounced in participants with a normal hippocampal volume. CONCLUSION: Microstructural integrity of the hippocampus assessed by DTI is related to verbal memory performance in elderly with SVD, also in participants with an intact appearing hippocampus. Changes in hippocampal microstructure may be an early marker of underlying neurodegenerative disease, before macrostructural (i.e., volumetric) changes occur.","Aged;Aged, 80 and over;Anisotropy;Cerebral Small Vessel Diseases/complications/ pathology;Cohort Studies;Diffusion Magnetic Resonance Imaging;Early Diagnosis;Female;Hippocampus/ pathology;Humans;Male;Memory/physiology;Memory Disorders/etiology/ pathology;Middle Aged","van Norden, A. G.;de Laat, K. F.;Fick, I.;van Uden, I. W.;van Oudheusden, L. J.;Gons, R. A.;Norris, D. G.;Zwiers, M. P.;Kessels, R. P.;de Leeuw, F. E.",2012,Mar,10.1002/hbm.21231,0,
615,A new mutation in the prion protein gene: A patient with dementia and white matter changes,"The authors describe the clinical characteristics, MRI abnormalities, and molecular findings in a patient with a novel variant of a two-octarepeat insertion mutation in the prion protein gene. This patient presented with moderately progressive dementia of presenile onset and gait ataxia. MRI showed extensive cortical atrophy and white matter abnormalities. The mutation consists of a two-octarepeat insertion mutation and irregularities in the nucleotide sequence of the octarepeat region.",DNA;prion protein;adult;article;case report;dementia;female;gene mutation;human;male;neurologic disease;nuclear magnetic resonance imaging;nucleotide sequence;polymerase chain reaction;priority journal;white matter,"Van Harten, B.;Van Gool, W. A.;Van Langen, I. M.;Deekman, J. M.;Meijerink, P. H. S.;Weinstein, H. C.",2000,,,0,
616,Brain lesions on MRI in elderly patients with type 2 diabetes mellitus,"BACKGROUND AND PURPOSE: Diabetes mellitus (DM) type 2 has been associated with poor cognitive performance and dementia, particularly in elderly patients. The exact mechanisms underlying the cognitive dysfunction in DM remain unclear. Imaging studies of the brain could be helpful to give more insight into possible structural brain lesions underlying these cognitive dysfunctions. Therefore, we performed a study in independently living patients with DM type 2 in order to investigate the association between DM and brain imaging abnormalities. METHODS: The study population consisted of 45 patients with DM type 2 without hypertension (mean age 73.4 +/- 5.1 years, mean duration 16.5 +/- 11.5 years), 45 patients with DM type 2 and hypertension (mean age 73.5 +/- 6.1 years, mean duration 11.9 +/- 9.2 years) and 44 control subjects (mean age 73.1 +/- 5.4 years). All patients and control subjects underwent an MRI of the brain. White matter lesions (WML), cerebral atrophy and medial temporal lobe atrophy were rated by a standardized visual rating scale. Lacunar infarcts were defined as focal hypo-intensities on fluid-attenuated inversion recovery sequences with a hyperintense rim around it. RESULTS: WML occurred more frequently in diabetic patients with hypertension as well as without hypertension. Significantly more deep WML were found in DM patients with and without hypertension when compared to control subjects, whereas no difference was found in the occurrence of periventricular hyperintensities. In all 3 groups, lacunar infarcts occurred sporadically. A trend towards higher atrophy scores was seen in patients with DM compared to control subjects. CONCLUSIONS: The data of this cross-sectional study suggest that type 2 DM is an independent risk factor for deep WML in the independently living elderly patients.","Aged;Brain/ pathology;Brain Diseases/blood/ etiology/ pathology;Cross-Sectional Studies;Diabetes Mellitus, Type 2/blood/ complications;Female;Hemoglobin A, Glycosylated/analysis;Humans;Hypertension/complications;Magnetic Resonance Imaging;Male;Risk Factors","van Harten, B.;Oosterman, J. M.;Potter van Loon, B. J.;Scheltens, P.;Weinstein, H. C.",2007,,10.1159/000098054,0,
617,The auditory oddball paradigm in patients with vascular cognitive impairment: a prolonged latency of the N2 complex,"OBJECTIVE: The event-related potential (ERP) evoked by the auditory oddball paradigm has been investigated mainly in patients with Alzheimer's disease and in patients with different causes of subcortical dementia. Subcortical ischemic vascular disease (SIVD) seems to be an important cause of vascular cognitive impairment (VCI) frequently not fulfilling the criteria for dementia. Recognition of VCI is needed in order to provide adequate care and therapy. The aim of this study was to investigate the diagnostic value of the different elements of this response (N(1), N(2) complex and P(3) latencies) in a group of elderly patients with VCI caused by SIVD. METHODS: The study population consisted of patients with a clinical and neuropsychological diagnosis of VCI caused by SIVD (n = 38) and healthy control subjects (n = 53) aged 60 years or older. The mean Mini Mental State Examination score of both groups was 27.6, and the mean HIV Dementia Scale score was 6.1 in the patient group and 12.3 in the control group. In all subjects, the ERP was recorded under standardized conditions, and the latencies and amplitudes of N(1), N(2) and P(3) were analyzed by two clinical neurophysiologists in consensus. Both were blinded to the diagnosis. RESULTS: The N(2) latency was significantly longer in patients with VCI than in age-matched controls, whereas the latencies of the P(3) and N(1) were not significantly different. The peak-to-peak amplitude of the N(2) complex to the P(3) wave was significantly lower in the patient group. White matter abnormalities on MRI were not significantly correlated with the N(2) latency. CONCLUSION: Our findings suggest that the latency of the N(2) complex is prolonged and the peak-to-peak amplitude of the N(2) complex to the P(3) wave is lowered in patients with VCI caused by SIVD.","Aged;Brain/*blood supply;Cerebrovascular Circulation/physiology;Cognition Disorders/*diagnosis/*epidemiology;Dementia, Vascular/*epidemiology/*physiopathology;Electroencephalography;Evoked Potentials, Auditory/*physiology;Female;Humans;Male;Neuropsychological Tests;Severity of Illness Index;Time Factors","van Harten, B.;Laman, D. M.;van Duijn, H.;Knol, D. L.;Stam, C. J.;Scheltens, P.;Weinstein, H. C.",2006,,10.1159/000091474,0,
618,Axonal tract tracing for delineating interacting brain regions: implications for Alzheimer's disease-associated memory,"We are studying the projections from the entorhinal cortex to the hippocampal formation in the mouse. The dentate gyrus is innervated by the lateral entorhinal cortex (lateral perforant path) and medial entorhinal cortex (medial perforant path). The entorhinal cortex also projects to hippocampal areas CA3 and CA1, and to the subiculum. In young transgenic Alzheimer's disease mouse models (before amyloid-beta pathology), the connections are not different from normal mice. In Alzheimer's disease mice with pathology, two changes occur: first, dystrophic axon endings appear near amyloid-beta plaques, and second, there are sparse aberrant axon terminations not in the appropriate area or lamina of the hippocampus. Furthermore, MRI-diffusion tensor imaging analysis indicates a decrease in the quality of the white matter tracts connecting the hippocampus to the brain; in other words, the fimbria/fornix and perforant path. Similar changes in white matter integrity have been found in Alzheimer's disease patients and could potentially be used as early indicators of disease onset.",,"van Groen, T.;Miettinen, P.;Kadish, I.",2014,Jan 1,10.2217/fnl.13.67,0,
619,Leukoaraiosis and vascular dementia,"The emergence of sensitive techniques for brain imaging has drawn attention to the occurrence of diffuse or multifocal changes affecting the cerebral white matter. The white matter changes are usually termed periventricular leukoencephalopathy, or leukoaraiosis. Microscopic studies of affected areas in the deep white matter have shown mostly demyelination, reactive gliosis, and arteriolosclerosis, proportional to the degree of radiologic changes. Yet, many other disease conditions need to be ruled out. Risk factors for ischemic leukoaraiosis include arterial hypertension, a history of stroke, and age. In the hereditary disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), severe white matter changes occur in the absence of hypertension. In 'ordinary' cases of leukoaraiosis, genetic factors might similarly determine the effect of risk factors on the aging brain and might explain, for example, why not all patients with severe hypertension develop leukoaraiosis. Not surprisingly, diffuse demyelination affects cognitive function. Although reduced speed of mental processes is the most characteristic sign, attention, concentration, and verbal and visual memory are also affected. Most importantly, less severe forms of cognitive impairment represent a silent and perhaps largely preventable epidemic among aged or even middle-aged subjects. They live independently, but mentally they perform on a level well below their previous capacities. Although being 'a bit odd' does not lead to hospital admissions, it seriously affects quality of life of a large part of the community. Moderate grades of leukoaraiosis constitute a major public health problem and deserve the attention of the scientific community.",,"Van Gijn, J.",1998,September,,0,
620,Caudate nucleus hypointensity in the elderly is associated with markers of neurodegeneration on MRI,"In this study we investigated patterns of hypointense basal ganglia on T2*-weighted magnetic resonance imaging (MRI) in 413 non-demented elderly (range: 70-82 years, mean 77 years; male/female: 177/239). In addition, we assessed associations between these patterns and age-related changes in the brain. Three patterns were noted: hypointensity limited to the globus pallidus (group I; n=30; 7%), hypointensity of both globus pallidus and putamen (group II; n=272; 66%), and hypointensity of globus pallidus, putamen and caudate nucleus (group III; n=111; 27%). Group III demonstrated a higher volume of white matter hyperintensities, more atrophy, decreased whole brain magnetization transfer ratios and increased T2-values compared to groups I and II. No differences were observed between groups I and II. From this study we conclude that hypointensity of the caudate nucleus is associated with a higher load of age-related cerebral changes. These data suggest that hypointensity of the caudate nucleus could be a new biomarker of age-related changes in the brain.","Aged;Aged, 80 and over;Aging/ pathology;Caudate Nucleus/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Neurodegenerative Diseases/ pathology;Reproducibility of Results;Sensitivity and Specificity","van Es, A. C.;van der Grond, J.;de Craen, A. J.;Admiraal-Behloul, F.;Blauw, G. J.;van Buchem, M. A.",2008,Dec,10.1016/j.neurobiolaging.2007.05.008,0,
621,Magnetization transfer imaging of gray and white matter in mild cognitive impairment and Alzheimer's disease,"OBJECTIVE: To assess whether structural brain damage as detected by magnetization transfer imaging (MTI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is located in the gray matter (GM) and/or the white matter (WM). METHODS: Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive function participated in this study. GM and WM segmentations were generated from dual fast spin-echo MR images. These masks were co-registrated to MT images for volumetric MTI-analysis of the GM and WM. RESULTS: AD patients had a lower GM volume than controls. Both MCI and AD patients had more structural brain damage in both GM and WM than subjects with normal cognition. Cerebral lesion load in both GM and WM was associated with the degree of cognitive impairment. CONCLUSION: Using MTI, structural brain changes that are related to cognitive impairment could be demonstrated in both GM and WM of patients with AD and MCI. These results suggest that cerebral changes are present in GM and WM even before patients are clinically demented.","Aged;Aged, 80 and over;Alzheimer Disease/complications/diagnosis/ pathology;Atrophy;Brain/pathology;Cerebral Cortex/ pathology;Cognition Disorders/complications/diagnosis/ pathology;Female;Humans;Image Enhancement/methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/ pathology","van Es, A. C.;van der Flier, W. M.;Admiraal-Behloul, F.;Olofsen, H.;Bollen, E. L.;Middelkoop, H. A.;Weverling-Rijnsburger, A. W.;Westendorp, R. G.;van Buchem, M. A.",2006,Dec,10.1016/j.neurobiolaging.2005.09.042,0,
622,Lobar distribution of changes in gray matter and white matter in memory clinic patients: detected using magnetization transfer imaging,"BACKGROUND AND PURPOSE: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline. MATERIALS AND METHODS: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage. RESULTS: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition. CONCLUSION: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.","Aged;Alzheimer Disease/ pathology/psychology;Brain/ pathology;Cognition Disorders/ pathology/psychology;Female;Frontal Lobe/pathology;Humans;Image Enhancement;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory;Occipital Lobe/pathology;Parietal Lobe/pathology;Temporal Lobe/pathology","van Es, A. C.;van der Flier, W. M.;Admiraal-Behloul, F.;Olofsen, H.;Bollen, E. L.;Middelkoop, H. A.;Weverling-Rijnsburger, A. W.;van der Grond, J.;Westendorp, R. G.;van Buchem, M. A.",2007,Nov-Dec,10.3174/ajnr.A0687,0,
623,MRI artifacts in human brain tissue after prolonged formalin storage,"For the interpretation of magnetic resonance imaging (MRI) abnormalities in brain pathology, often ex vivo tissue is used. The purpose of this study was to determine the pathological substrate of several distinct forms of MR hypointensities that were found in formalin-fixed brain tissue with amyloid-beta deposits. Samples of brain cortex were scanned using effective transverse relaxation time-weighted protocols at several resolutions on a 9.4 T MRI scanner. High resolution MRI showed large coarse hypointensities throughout the cortical gray and white matter, corresponding to macroscopic discolorations and microscopic circumscribed areas of granular basophilic neuropil changes, without any further specific tissue reactions or amyloid-beta related pathology. These coarse MRI hypointensities were identified as localized areas of absent neuropil replaced by membrane/myelin sheath remnants using electron microscopy. Interestingly, the presence/absence of these tissue alterations was not related to amyloid deposits, but strongly correlated to the fixation time of the samples in unrefreshed formalin. These findings show that prolonged storaged of formalin fixed brain tissue results in subtle histology artifacts, which show on MRI as hypointensities that on first appearance are indistinguishable from genuine brain pathology. This indicates that postmortem MRI should be interpreted with caution, especially if the history of tissue preservation is not fully known. © 2011 Wiley-Liss, Inc.",,"Van Duijn, S.;Nabuurs, R. J. A.;Van Rooden, S.;Maat-Schieman, M. L. C.;Van Duinen, S. G.;Van Buchem, M. A.;Van Der Weerd, L.;Natté, R.",2011,June,,0,
624,Venous congestive encephalopathy related to cranial dural arteriovenous fistulas,Cranial DAVFs present with a wide spectrum of clinical findings from pulsatile tinnitus alone to intracranial hemorrhage and NHND. The neurologic sequelae are a consequence of venous hypertension and venous congestion. DAVFs with CVR can present with or develop a VCE that can be recognized on,,"Van Dijk, J. M. C.;Willinsky, R. A.",2003,February,,0,
625,"Arterial oxygen saturation, COPD, and cerebral small vessel disease","OBJECTIVE: To study whether lower arterial oxygen saturation (SaO(2)) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. METHODS: We measured SaO(2) twice with a pulse oximeter, assessed the presence of COPD, and performed MRI in 1077 non-demented people from a general population (aged 60-90 years). We rated periventricular white matter lesions (on a scale of 0-9) and approximated a total subcortical white matter lesion volume (range 0-29.5 ml). All analyses were adjusted for age and sex and additionally for hypertension, diabetes, body mass index, pack years smoked, cholesterol, haemoglobin, myocardial infarction, and left ventricular hypertrophy. RESULTS: Lower SaO(2) was independent of potential confounders associated with more severe periventricular white matter lesions (score increased by 0.12 per 1% decrease in SaO(2) (95% confidence interval 0.01 to 0.23)). Participants with COPD had more severe periventricular white matter lesions than those without (adjusted mean difference in score 0.70 (95% confidence interval 0.23 to 1.16)). Lower SaO(2) and COPD were not associated with subcortical white matter lesions or lacunar infarcts. CONCLUSION: Lower SaO(2) and COPD are associated with more severe periventricular white matter lesions.","Aged;Body Mass Index;*Brain/blood supply/metabolism/pathology;Brain Infarction/*complications/*metabolism/pathology;Cholesterol/blood;Diabetes Mellitus/epidemiology;Female;Hemoglobins/metabolism;Humans;Hypertension/epidemiology;Hypertrophy, Left Ventricular/epidemiology/pathology;Magnetic Resonance Imaging;Male;Myocardial Infarction/epidemiology;Oximetry/methods;Oxygen/*metabolism;Pulmonary Disease, Chronic Obstructive/*complications/*metabolism;Smoking/epidemiology","van Dijk, E. J.;Vermeer, S. E.;de Groot, J. C.;van de Minkelis, J.;Prins, N. D.;Oudkerk, M.;Hofman, A.;Koudstaal, P. J.;Breteler, M. M.",2004,May,,0,
626,Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study,"BACKGROUND AND PURPOSE: Cerebral white matter lesions and lacunar infarcts are small vessel disease-related lesions, which are associated with cognitive decline and dementia. We aimed to assess the relationship between risk factors, effect modifiers, and progression of these lesions. Furthermore, we studied the cognitive consequences of lesion progression. METHODS: Six hundred sixty-eight people, aged 60 to 90 years, underwent repeated MRI scanning and neuropsychological testing within 3-year follow-up. We rated incident lacunar infarcts and change in periventricular and subcortical white matter lesion severity with a semiquantitative scale. We assessed the relationships between age, sex, baseline lesion load, risk factors, lesion progression, and change in cognitive function by multivariate regression analyses and additional stratified analyses. RESULTS: Baseline lesion load, higher age, high blood pressure, and current smoking were independently associated with progression of white matter lesions. Women had more marked progression of subcortical white matter lesions and incident lacunar infarcts compared with men. Carotid atherosclerosis was associated with incident lacunar infarcts. Higher blood pressure did not contribute to lesion progression in people with already severe lesions at baseline nor in the very old. Lesion progression was associated with a paralleled decline in general cognitive function and in particular with a decreased information processing speed. CONCLUSIONS: Higher age, female sex, cigarette smoking, elevated blood pressure, and baseline lesion load were associated with small vessel disease progression. Age and baseline lesion load influenced the risk relations with blood pressure. Progression of small vessel disease was related to a paralleled decline in cognitive function.","Age Factors;Aged;Aged, 80 and over;Blood Pressure/physiology;Brain/*blood supply/pathology;Brain Infarction/*complications/*pathology;Cognition Disorders/*etiology/*pathology/psychology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Sex Factors;Smoking/adverse effects","van Dijk, E. J.;Prins, N. D.;Vrooman, H. A.;Hofman, A.;Koudstaal, P. J.;Breteler, M. M.",2008,Oct,10.1161/strokeaha.107.513176,0,
627,C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study,"BACKGROUND: Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts. METHODS AND RESULTS: We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts. CONCLUSIONS: Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.","Aged;Aged, 80 and over;Biomarkers/blood;C-Reactive Protein/*metabolism;Cerebrovascular Disorders/blood/*epidemiology;Cohort Studies;Diabetes Mellitus/epidemiology;Female;Follow-Up Studies;Humans;Hypertension/epidemiology;Inflammation/blood/epidemiology;Male;Microcirculation/*physiopathology;Middle Aged;Netherlands/epidemiology;Risk Factors","van Dijk, E. J.;Prins, N. D.;Vermeer, S. E.;Vrooman, H. A.;Hofman, A.;Koudstaal, P. J.;Breteler, M. M.",2005,Aug 9,10.1161/circulationaha.104.506337,0,
628,"Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions","Lacunar brain infarcts and cerebral white matter lesions are frequently observed on magnetic resonance imaging scans in elderly subjects. These lesions are also frequent in patient with cerebral amyloid angiopathy. We examined whether plasma amyloid beta peptide (Abeta) levels are associated with lacunar infarcts and white matter lesions in the general population, and whether the apolipoprotein E (APOE) genotype modifies these associations. We studied 1,077 participants within the population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia. Cross-sectional associations were analyzed by regression models with adjustments for age, sex, creatinine levels, and hypertension. In APOE epsilon4 carriers, plasma Abeta levels were positively associated with lacunar infarcts and white matter lesions, whereas in noncarriers no associations were observed. Per standard deviation increase in Abeta(1-40) and Abeta(1-42) levels the odds ratios for lacunar infarcts were 1.72 (95% confidence interval [CI] = 1.22-2.43) and 1.93 (95% CI = 1.31-2.85), the periventricular white matter lesion grade increased by 0.32 (95% CI = 0.08-0.57) and 0.29 (95% CI = 0.00-0.57), and the subcortical white matter lesion volume increased by 0.48 ml (95% CI = 0.04-0.91) and 0.24 ml (95% CI = -0.27-0.75). Higher Abeta levels are associated with more lacunar infarcts and white matter lesions in elderly subjects who carry an APOE epsilon4 allele.","Aged;Aged, 80 and over;Amyloid beta-Peptides/ blood/genetics;Apolipoprotein E4;Apolipoproteins E/ genetics;Brain Infarction/ blood/genetics/ pathology;Confidence Intervals;Cross-Sectional Studies;Female;Humans;Linear Models;Male;Middle Aged;Nerve Fibers, Myelinated/metabolism/ pathology;Odds Ratio","van Dijk, E. J.;Prins, N. D.;Vermeer, S. E.;Hofman, A.;van Duijn, C. M.;Koudstaal, P. J.;Breteler, M. M.",2004,Apr,10.1002/ana.20050,0,
629,"The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study","Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account.",Aged;Aging/ physiology;Blood Pressure/ physiology;Brain/ pathology;Dementia/epidemiology;Female;Humans;Hypertension/ physiopathology;Magnetic Resonance Imaging;Male;Risk Factors;Stroke/epidemiology,"van Dijk, E. J.;Breteler, M. M.;Schmidt, R.;Berger, K.;Nilsson, L. G.;Oudkerk, M.;Pajak, A.;Sans, S.;de Ridder, M.;Dufouil, C.;Fuhrer, R.;Giampaoli, S.;Launer, L. J.;Hofman, A.",2004,Nov,10.1161/01.hyp.0000145857.98904.20,0,
630,Associations between magnetic resonance imaging measures and neuropsychological impairment in early and late onset alzheimer's disease,"AIM: To assess the associations of global atrophy and white matter hyperintensities (WMH) with neuropsychological function in early and late onset Alzheimer's disease (AD). METHODS: We included 107 patients with sporadic AD (21 early onset and 86 late onset) from our memory clinic. Tests for (working) memory, language, executive function, mental speed, and attention were administered. Global atrophy and global and lobar WMH were measured using 1 Tesla MRI. Linear regression analyses with terms for MRI measures, neuropsychological test results, age, gender, education, and the interaction between separate brain measures and age of onset were performed. RESULTS: Global atrophy was associated with more severely impaired global cognition, working memory, mental speed, and executive function (p < 0.05). Significant interactions between global atrophy and age at onset showed that these associations were mostly attributable to patients with early onset AD. By contrast, an association between global atrophy and memory was found, which was specifically attributable to late onset AD patients. No associations between global WMH and cognitive function were found. Subsequently we analyzed regional WMH and found that temporal WMH was associated with impaired memory, and frontal WMH was associated with slower mental speed. CONCLUSION: Cortical atrophy, a key feature of AD, is linked to a wide range of cognitive functions, specifically in early onset AD patients. For WMH, there were no interactions with age at onset, but we found specific associations between temporal WMH and memory and frontal WMH and mental speed.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/metabolism/ psychology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neuropsychological Tests","van der Vlies, A. E.;Staekenborg, S. S.;Admiraal-Behloul, F.;Prins, N. D.;Barkhof, F.;Vrenken, H.;Reiber, J. H.;Scheltens, P.;van der Flier, W. M.",2013,,10.3233/jad-121291,0,
631,Microbleeds do not affect rate of cognitive decline in Alzheimer disease,"OBJECTIVE: To investigate the relationship between brain microbleeds (MBs) and the rate of cognitive decline in Alzheimer disease (AD). METHODS: In this cohort study, we studied 221 patients with AD with available baseline MRI scans (1.0 or 1.5 T) and at least 2 Mini-Mental State Examinations (MMSE) scores obtained more than 1 year apart from our memory clinic. Mean +/- SD follow-up time was 3 +/- 1 years, and patients had a median of 4 MMSE scores (range 2-17). We used linear mixed models with sex and age as covariates to investigate whether MBs influenced the rate of cognitive decline. RESULTS: Mean age was 68 +/- 9 years, 109 (49%) patients were female, and the baseline MMSE score was 22 +/- 4. There were 39 patients (18%) with MBs (median 2, range 1-27) and 182 without. Linear mixed models showed that overall patients declined 2 MMSE points per year. We found no association of the presence of MBs with baseline MMSE or change in MMSE. Adjustment for atrophy, white matter hyperintensities, lacunes, and vascular risk factors did not change the results nor did stratification for MB location, APOE epsilon4 carriership, or age at onset (</=65 years vs >65 years). Repeating the analyses with number of MBs as predictor rendered similar results. CONCLUSION: MBs did not influence the rate of cognitive decline in patients with AD. The formerly reported increased risk of mortality in patients with MBs seems not to be attributable to a steeper rate of decline per se but might be due to vascular events, including (hemorrhagic) stroke.","Age of Onset;Aged;Alzheimer Disease/cerebrospinal;fluid/complications/genetics/pathology/*psychology;Amyloid beta-Peptides/*cerebrospinal fluid;Apolipoprotein E4/genetics;Atrophy/pathology;Biomarkers/cerebrospinal fluid;Cerebral Hemorrhage/cerebrospinal fluid/complications/pathology/*psychology;Cognition Disorders/cerebrospinal fluid/complications/pathology/*psychology;Cohort Studies;Disease Progression;Female;Humans;Magnetic Resonance Imaging/methods/psychology;Male;Nerve Fibers, Myelinated/pathology;Neuroimaging/methods/*psychology;Neuropsychological Tests/statistics & numerical data;Peptide Fragments/*cerebrospinal fluid;Risk Factors;tau Proteins/*cerebrospinal fluid","van der Vlies, A. E.;Goos, J. D.;Barkhof, F.;Scheltens, P.;van der Flier, W. M.",2012,Aug 21,10.1212/WNL.0b013e3182661f91,0,
632,Hypertensive Target Organ Damage and Longitudinal Changes in Brain Structure and Function: The Second Manifestations of Arterial Disease-Magnetic Resonance Study,"Hypertension has been related to structural and functional brain changes. In high-risk populations, hypertensive target organ damage might better represent exposure to high blood pressure than the blood pressure measurement itself. We examined the association of hypertensive target organ damage with longitudinal changes in brain structure and function within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study. Renal function, albuminuria, and left ventricular hypertrophy on electrocardiography were measured in 663 patients with manifest arterial disease (mean age, 57±9 years; 81% men). Automated brain segmentation was used to quantify progression of global brain atrophy (change in brain parenchymal fraction) and progression of cerebral small vessel disease on 1.5T magnetic resonance imaging, and memory and executive functioning were assessed at baseline and after on average 3.9 years of follow-up. Regression analyses showed that an increasing number of signs of target organ damage was associated with more progression of global brain atrophy and more rapid decline in memory performance. Compared with no target organ damage, mean differences in change in brain parenchymal fraction (95% confidence interval) for 1 and ≥2 signs of organ damage were -0.12 (-0.30; 0.06) and -0.41 (-0.77; -0.05) % intracranial volume, and mean (95% confidence interval) differences in change in memory performance (z score) were -0.15 (-0.29; -0.00) and -0.27 (-0.54; -0.01). Results were independent of blood pressure, antihypertensive treatment, and other confounders. Hypertension target organ damage was not associated with progression of cerebral small vessel disease or change in executive functioning. Routinely assessed signs of hypertensive target organ damage, and in particular impaired renal function, could be used to identify patients at the highest risk of cognitive decline.",,"Van Der Veen, P. H.;Geerlings, M. I.;Visseren, F. L. J.;Nathoe, H. M.;Mali, W. P. T. M.;Van Der Graaf, Y.;Muller, M.;Algra, A.;Doevendans, P. A.;Grobbee, D. E.;Rutten, G. E. H. M.;Kappelle, L. J.;Moll, F. L.",2015,1,,0,
633,Neonatal porencephaly and adult stroke related to mutations in collagen IV A1,"Objective: The objective of this study was to describe leukoencephalopathy, lacunar infarcts, microbleeds and macrobleeds in the context of a collagen",,"Van Der Knaap, M. S.;Smit, L. M. E.;Barkhof, F.;Pijnenburg, Y. A. L.;Zweegman, S.;Niessen, H. W. M.;Imhof, S.;Heutink, P.",2006,March,,0,
634,Cerebellar leukoencephalopathy: Most likely histiocytosis-related,"Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called ""neurodegenerative syndromeg"" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome. Methods: We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI. Results: All patients were isolated cases; 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates. Conclusions: Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis. © 2008 by AAN Enterprises, Inc.",CD68 antigen;CD8 antigen;growth hormone;adolescent;adult;article;basal ganglion;behavior disorder;brain biopsy;brain calcification;brain cortex;brain stem;cell infiltration;cerebellar ataxia;cerebellum;cerebellum leukoencephalopathy;child;clinical article;dendritic cell;diabetes insipidus;diffusion weighted imaging;female;growth hormone deficiency;histiocyte;histiocytosis;human;human tissue;hypothyroidism;Langerhans cell;leukoencephalopathy;macrophage;male;mental deterioration;metabolic disorder;monocyte;neuroimaging;precocious puberty;preschool child;priority journal;pyramidal tract;retrospective study;school child;spasticity;spinal cord;spinal cord lesion;white matter,"Van Der Knaap, M. S.;Arts, W. F. M.;Garbern, J. Y.;Hedlund, G.;Winkler, F.;Barbosa, C.;King, M. D.;Bjørnstad, A.;Hussain, N.;Beyer, M. K.;Gomez, C.;Patterson, M. C.;Grattan-Smith, P.;Timmons, M.;Van Der Valk, P.",2008,,,0,
635,Microstructural integrity of the cingulum is related to verbal memory performance in elderly with cerebral small vessel disease: the RUN DMC study,"BACKGROUND: Cerebral small vessel disease (SVD) is related to verbal memory failures. It is suggested that early white matter damage, is located, among others, in the (posterior) cingulum at an early stage in neurodegeneration. Changes in the microstructural integrity of the cingulum assessed with diffusion tensor imaging (DTI), beyond detection with conventional MRI, may precede macrostructural changes and be related to verbal memory failures. OBJECTIVE: To investigate the relation between cingular microstructural integrity and verbal memory performance in 503 non-demented elderly with cerebral SVD. METHODS: The RUN DMC study is a prospective cohort study in elderly (50-85 years) with cerebral SVD. All participants underwent T1 MPRAGE, FLAIR and DTI scanning and the Rey Auditory Verbal Learning Test. Mean diffusivity (MD) and fractional anisotropy (FA) were assessed in six different cingular regions of interests (ROIs). Linear regression analysis was used to assess the relation between verbal memory performance and cingular DTI parameters, with appropriate adjustments. Furthermore a TBSS analysis of the whole brain was performed to investigate the specificity of our findings. RESULTS: Both our ROI-based and TBSS analysis showed that FA was positively related to immediate memory, delayed recall, delayed recognition and overall verbal memory performance of the cingulum, independent of confounders. A similar distribution was seen for the inverse association with MD and verbal memory performance with TBSS analysis. No significant relations were found with psychomotor speed, visuospatial memory and MMSE. When stratified on hippocampal integrity, the MD and FA values of the cingular ROIs differed significantly between participants with a good and poor hippocampal integrity. CONCLUSION: Microstructural integrity of the cingulum, assessed by DTI, is specifically related to verbal memory performance, in elderly with SVD. Furthermore we found that when the integrity of the hippocampus is disrupted, the cingulum integrity is impaired as well.","Aged;Aged, 80 and over;Cerebral Small Vessel Diseases/complications/ pathology;Cohort Studies;Diffusion Magnetic Resonance Imaging;Female;Gyrus Cinguli/ pathology;Humans;Image Interpretation, Computer-Assisted;Male;Memory;Memory Disorders/complications/ pathology;Middle Aged;Neuropsychological Tests","van der Holst, H. M.;Tuladhar, A. M.;van Norden, A. G.;de Laat, K. F.;van Uden, I. W.;van Oudheusden, L. J.;Zwiers, M. P.;Norris, D. G.;Kessels, R. P.;de Leeuw, F. E.",2013,Jan 15,10.1016/j.neuroimage.2012.09.060,0,
636,Small vessel disease and general cognitive function in nondisabled elderly: The LADIS study,"Background and Purpose - On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. Methods - Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). Results - In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. Conclusion - We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function. © 2005 American Heart Association, Inc.",,"Van Der Flier, W. M.;Van Straaten, E. C. W.;Barkhof, F.;Verdelho, A.;Madureira, S.;Pantoni, L.;Inzitari, D.;Erkinjuntti, T.;Crisby, M.;Waldemar, G.;Schmidt, R.;Fazekas, F.;Scheltens, P.",2005,October,,0,
637,Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study,"OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.","Aged;Atrophy/complications/pathology;Cognition Disorders/ diagnosis/etiology;Disability Evaluation;Female;Humans;Leukoaraiosis/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Neurofibrillary Tangles/pathology;Neuropsychological Tests;Plaque, Amyloid/pathology;Prospective Studies;Severity of Illness Index;Temporal Lobe/ pathology","van der Flier, W. M.;van Straaten, E. C.;Barkhof, F.;Ferro, J. M.;Pantoni, L.;Basile, A. M.;Inzitari, D.;Erkinjuntti, T.;Wahlund, L. O.;Rostrup, E.;Schmidt, R.;Fazekas, F.;Scheltens, P.",2005,Nov,10.1136/jnnp.2005.064998,0,
638,MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic,"Objective: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. Methods: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. Results: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. Conclusions: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline. Copyright © 2005 John Wiley & Sons, Ltd.",,"van der Flier, W. M.;van der Vlies, A. E.;Weverling-Rijnsburger, A. W. E.;de Boer, N. L.;Admiraal-Behloul, F.;Bollen, E. L. E. M.;Westendorp, R. G. J.;van Buchem, M. A.;Middelkoop, H. A. M.",2005,November,,0,
639,Interaction of medial temporal lobe atrophy and white matter hyperintersities in AD,"The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.",aged;Alzheimer disease;article;brain atrophy;controlled study;disease association;female;histopathology;human;major clinical study;male;priority journal;quantitative diagnosis;risk assessment;statistical significance;syndrome delineation;temporal lobe;vascular disease;white matter,"Van Der Flier, W. M.;Middelkoop, H. A. M.;Weverling-Rijnsburger, A. W. E.;Admiraal-Behloul, F.;Spilt, A.;Bollen, E. L. E. M.;Westendorp, R. G. J.;Van Buchem, M. A.",2004,,,0,
640,Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD,"The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.","Aged;Alzheimer Disease/complications/*pathology;Atrophy;Dementia, Vascular/complications/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Myelin Sheath/pathology;Temporal Lobe/*pathology","van der Flier, W. M.;Middelkoop, H. A.;Weverling-Rijnsburger, A. W.;Admiraal-Behloul, F.;Spilt, A.;Bollen, E. L.;Westendorp, R. G.;van Buchem, M. A.",2004,May 25,,0,
641,Neuropsychological correlates of MRI measures in the continuum of cognitive decline at old age,"OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/psychology;Atrophy;Brain/*pathology;Cognition Disorders/*pathology/*psychology;Disease Progression;Female;Humans;Language;*Magnetic Resonance Imaging;Male;Memory/physiology;Neuropsychological Tests;Psychomotor Performance;Regression Analysis;Temporal Lobe/pathology","van der Flier, W. M.;Middelkoop, H. A.;Weverling-Rijnsburger, A. W.;Admiraal-Behloul, F.;Bollen, E. L.;Westendorp, R. G.;van Buchem, M. A.",2005,,10.1159/000086072,0,
642,Microbleeds in vascular dementia: Clinical aspects,"Microbleeds are small dot-like lesions which can be appreciated on gradient echo, T2*-weighted magnetic resonance images as hypointensities. They are considered as an expression of small vessel disease on MRI, next to lacunes and white matter hyperintensities (WMH). Microbleeds are relatively common in vascular dementia, with reported prevalences between 35% and 85%. In the context of vascular dementia, microbleeds are mainly thought to result from hypertensive vasculopathy, but the frequent co-occurrence of lobar microbleeds suggests that neurodegenerative pathology and/or cerebral amyloid angiopathy is also of importance. The presence of multiple microbleeds in vascular dementia or in patients with vascular cognitive impairment is related to worse performance on cognitive tests, mainly in psychomotor speed and executive functioning. They may have some predictive value in terms of predicting development of (vascular) dementia, mortality and disability. Data on the occurrence of stroke and post-stroke dementia in patients with microbleeds are to date not available. New definitions and diagnostic criteria for vascular dementia and vascular cognitive impairment are needed and should take into account microbleeds. © 2012 Elsevier Inc.",,"Van der Flier, W. M.;Cordonnier, C.",2012,November,,0,
643,Clinical aspects of microbleeds in Alzheimer's disease,"Microbleeds are small lesions, appearing as black dots on T2*-weighted magnetic resonance imaging. They occur frequently in Alzheimer's disease (AD), but the clinical relevance of these radiological observations remains unclear. In this paper an overview is given on currently available evidence on the clinical relevance of microbleeds in AD. The evidence linking microbleeds to severity of cognitive impairment in AD is not unambiguous. From the existing literature, it seems reasonable to conclude that multiple microbleeds negatively impact cognitive performance, but there is less consensus on the importance of location of microbleeds in this respect. Regarding progression of disease, there is hardly any evidence that microbleeds affect disease course in terms of progression to AD in patients with MCI or with respect to rate of cognitive decline in AD patients. This may imply that microbleeds simply do not affect disease course, but an alternative explanation for the negative findings would be that these studies are hampered by selective drop-out, as individuals with many microbleeds have an increased risk of (stroke-related) mortality. © 2012 Elsevier B.V.",,"Van Der Flier, W. M.",2012,15,,0,
644,Measuring longitudinal white matter changes: Comparison of a visual rating scale with a volumetric measurement,"BACKGROUND AND PURPOSE: Detection of longitudinal changes in white matter hyperintensities (WMH) by using visual rating scales is problematic. We compared a widely used visual rating scale with a volumetric method to study longitudinal white matter changes. METHODS: WMH were assessed with the visual Scheltens scale and a volumetric method in 100 elderly subjects aged 70-81 years for whom repetitive MR images were available with an interval of 33 (SD, 1.4) months. Reliability was determined by intraclass correlation coefficients. To examine the sensitivity of both the visual and volumetric method, we calculated Spearman rank correlations of WMH ratings and volume measurements with age. RESULTS: Reliability of the visual rating scale was good, whereas reliability of the volumetric measurement was excellent. For baseline measurements of WMH, we found weaker associations between WMH and age when assessed with the visual scale (r = 0.20, P = .045) than with the volumetric method (r = 0.31, P = .002). Longitudinal evaluation of WMH assessments showed regression in 26% of the subjects when analyzed with the visual rating scale against 12% of the subjects when using volumetric measurements. Compared with the visual rating, the correlation between progression in WMH and age was twice as high when using the volumetric measurement (r= 0.19, P =.062 and r = 0.39, P< .001, respectively). CONCLUSION: Volumetric measurements of WMH offer a more reliable, sensitive, and objective alternative to visual rating scales in studying longitudinal white matter changes.",,"Van Den Heuvel, D. M. J.;Ten Dam, V. H.;De Craen, A. J. M.;Admiraal-Behloul, F.;Van Es, A. C. G. M.;Palm, W. M.;Spilt, A.;Bollen, E. L. E. M.;Blauw, G. J.;Launer, L.;Westendorp, R. G. J.;Van Buchem, M. A.",2006,April,,0,
645,Subcortical lacunar lesions: An MR imaging finding in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"PURPOSE: To assess the prevalence and distribution of subcortical lacunar lesions (SLLs) in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to determine whether SLLs are an abnormal finding by studying their prevalence in healthy subjects, and to assess whether SLLs occur in other conditions associated with small vessel disease and white matter areas of high signal intensity (WMH). MATERIALS AND METHODS: The presence of SLLs, their location, and their relation to other abnormalities were assessed on magnetic resonance (MR) images (T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery) obtained in 34 CADASIL patients and 20 healthy family members. Three additional control groups of healthy volunteers, elderly patients with vascular risk factors, and patients with another hereditary small vessel disease were also screened for the presence and location of SLLs. Sensitivity and specificity of the presence of SLLs for the diagnosis of CADASIL were assessed. RESULTS: SLLs were found in 20 (59%) of CADASIL patients. Incidence of SLLs increased with age (20%, <30 years; 50%, 30-50 years; 80%, >50 years). SLLs invariably occurred in the anterior temporal lobes and in areas where diffuse WMH expanded into arcuate fibers. From the anterior temporal lobe, the lesions could extend dorsally into the temporal lobes and rostrally into the frontal lobes. Lesions were not found in the parietal and occipital lobes. None of the control subjects had SLLs. Specificity and sensitivity of SLLs for CADASIL were 100% and 59%, respectively. CONCLUSION: SLLs are an abnormal finding at MR imaging that frequently occur in CADASIL patients. © RSNA, 2002.",,"Van den Boom, R.;Lesnik Oberstein, S. A. J.;Van Duinen, S. G.;Bornebroek, M.;Ferrari, M. D.;Haan, J.;Van Buchem, M. A.",2002,September,,0,
646,Cerebral hemodynamics and white matter hyperintensities in CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white matter hyperintensities and lacunar infarcts. The authors used phase-contrast MRI in 40 NOTCH3 mutation carriers (mean age 45 +/- 10 years) and 22 nonmutated family members (mean age 39 +/- 12 years), to assess baseline total cerebral blood flow (TCBF) and cerebrovascular reactivity after acetazolamide. Mean baseline TCBF was significantly decreased in NOTCH3 mutation carriers. In young subjects, baseline TCBF was significantly lower than in nonmutation carriers (mean difference 124 mL/min). Furthermore, baseline TCBF did not differ significantly between mutation carriers with minimal and mutation carriers with moderate or severe white matter hyperintensities. No significant difference in mean cerebrovascular reactivity was found between mutation carriers and nonmutation carriers. This study suggests that a decrease in baseline TCBF in NOTCH3 mutation carriers precedes the development of white matter hyperintensities.","Adult;Brain Infarction/genetics/pathology/physiopathology;Cerebrovascular Circulation/ physiology;Dementia, Multi-Infarct/genetics/ pathology/ physiopathology;Family;Female;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers/pathology;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface;Receptors, Notch;Severity of Illness Index","van den Boom, R.;Lesnik Oberstein, S. A.;Spilt, A.;Behloul, F.;Ferrari, M. D.;Haan, J.;Westendorp, R. G.;van Buchem, M. A.",2003,May,10.1097/01.wcb.0000062341.61367.d3,0,
647,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages--3rd-6th decades,"PURPOSE: To depict various brain lesions that have been described in patients who have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with prospective standardized magnetic resonance (MR) imaging in patients of different age groups. MATERIALS AND METHODS: Forty patients with CADASIL in different age groups (20-30 years, n = 5; 31-40 years, n = 4; 41-50 years, n = 16; 51-60 years, n = 15) underwent transverse MR imaging with T1-weighted dual fast spin-echo, fluid-attenuated inversion-recovery, and T2*-weighted gradient-echo sequences. Images were analyzed by one neuroradiologist for the presence of areas of hyperintensity, lacunar infarcts, microbleeds, and subcortical lacunar lesions (SLLs) in different anatomic locations. Descriptive statistics were obtained for the presence of MR imaging abnormalities in various brain areas and for distribution according to age. RESULTS: The mean age of the 40 mutation carriers (21 women, 19 men) was 45 years +/- 10 (SD). In patients with CADASIL who were 20-30 years old, characteristic hyperintense lesions in the anterior temporal lobe (100% [five of five]) and SLLs (20% [one of five]) were the only abnormalities seen on MR images. In patients who were 30-40 years old, lacunar infarcts were found in 75% (three of four) of cases. More areas of hyperintensity were noted, and they frequently involved the external capsule, basal ganglia, and brainstem. In patients 41-50 years old, microbleeds were observed in 19% (three of 16). In patients older than 50 years, areas of hyperintensity (100% [15 of 15]), SLLs (73% [11 of 15]), lacunar infarcts (93% [14 of 15]), and microbleeds (47% [seven of 15]) were frequently observed. CONCLUSION: The four types of brain lesions that are observed in patients with CADASIL were seen in patients of different age groups.","Adult;Age Factors;Dementia, Multi-Infarct/ diagnosis/genetics;Female;Heterozygote;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mutation;Temporal Lobe/pathology","van den Boom, R.;Lesnik Oberstein, S. A.;Ferrari, M. D.;Haan, J.;van Buchem, M. A.",2003,Dec,10.1148/radiol.2293021354,0,
648,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Structural MR imaging changes and apolipoprotein E genotype,"BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) genotype plays an important role in the development, maintenance, and response to injury of the central nervous system. It has been suggested that apoE ε4 genotype is a risk factor for several neurologic disorders. We investigated the correlation between the apoE genotype and radiologie data in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: T1-weighted, dual fast spin-echo, T2*-weighted gradient echo, and fluid-attenuated inversion recovery MR imaging scans were obtained from 36 CADASIL patients (21-59 years of age). The number of lacunar infarcts and microbleeds and the presence of subcortical lacunar lesions were determined. The amount of white matter hyperintensities was assessed by using semiautomated segmentation software. The relation between the radiologic endophenotype of CADASIL and the apoE genotype was assessed by using a Student t test for unpaired data and Fisher exact test. RESULTS: White matter hyperintensities, lacunar infarcts, microbleeds, and subcortical lacunar lesions were not found to be associated with the presence of an ε4 allele. CONCLUSION: The variability of structural MR imaging lesions in CADASIL is independent of apoE genotype and other processes must underlie the variable natural history of the disease.",,"Van Den Boom, R.;Lesnick Oberstein, S. A. J.;Van Den Berg-Huysmans, A. A.;Ferrari, M. D.;Van Buchem, M. A.;Haan, J.",2006,February,,0,
649,Magnetization transfer imaging in premanifest and manifest Huntington disease,"BACKGROUND AND PURPOSE: MTI has the potential to detect abnormalities in normal-appearing white and gray matter on conventional MR imaging. Early detection methods and disease progression markers are needed in HD research. Therefore, we investigated MTI parameters and their clinical correlates in premanifest and manifest HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 78 participants (28 controls, 25 PMGC, 25 MHD) were included. Brain segmentation of cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed using FSL's automated tools FAST and FIRST. Individual MTR values were calculated from these regions and MTR histograms constructed. Regression analysis of MTR measures from all gene carriers with clinical measures was performed. RESULTS: MTR peak height was reduced in both cortical gray (P = .01) and white matter (P = .006) in manifest HD compared with controls. Mean MTR was also reduced in cortical gray matter (P = .01) and showed a trend in white matter (P = .052). Deep gray matter structures showed a uniform pattern of reduced MTR values (P < .05). No differences between premanifest gene carriers and controls were found. MTR values correlated with disease burden and motor and cognitive impairment. CONCLUSIONS: Throughout the brain, disturbances in MTI parameters are apparent in early HD and are homogeneous across white and gray matter. The correlation of MTI with clinical measures indicates the potential to act as a disease monitor in clinical trials. However, our study does not provide evidence for MTI as a marker in premanifest HD.",Adult;Brain/ pathology;Early Diagnosis;Humans;Huntington Disease/ pathology;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Reproducibility of Results;Sensitivity and Specificity,"van den Bogaard, S. J.;Dumas, E. M.;Milles, J.;Reilmann, R.;Stout, J. C.;Craufurd, D.;van Buchem, M. A.;van der Grond, J.;Roos, R. A.",2012,May,10.3174/ajnr.A2868,0,
650,Magnetization transfer imaging in premanifest and manifest huntington disease: a 2-year follow-up,"BACKGROUND AND PURPOSE: MTI is a quantitative MR imaging technique that has recently demonstrated structural integrity differences between controls and patients with HD. Potentially, MTI can be used as a biomarker for monitoring disease progression. To establish the value of MTI as a biomarker, we aimed to examine the change in these measures during the course of HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 25 controls, 21 premanifest gene carriers, and 21 patients with manifest HD participated at baseline and during a 2-year follow-up visit. Brain segmentation of the cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed by using the automated tools FAST and FIRST in FSL. Individual MTR values were calculated from these regions, and MTR histograms were constructed. RESULTS: In the premanifest HD group stage ""far from disease onset,"" a significant increase in MTR peak height of the putamen was observed with time. During the manifest HD stage, neither the mean MTR nor the MTR peak height showed a significant change during a 2-year follow-up. CONCLUSIONS: MTI-derived measures are not suitable for monitoring in Huntington disease during a 2-year period because there was no decrease in structural integrity detected in any of the manifest HD groups longitudinally. The finding of increased putaminal MTR peak height in the premanifest far from disease onset group could relate to a predegenerative process, compensatory mechanisms, or aberrant development but should be interpreted with caution until future studies confirm this finding.","Adult;Amygdala/pathology;Basal Ganglia/pathology;Brain/ pathology;Cerebral Cortex/pathology;Disease Progression;Follow-Up Studies;Hippocampus/pathology;Humans;Huntington Disease/genetics/ pathology;Image Interpretation, Computer-Assisted/ methods;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Middle Aged;Thalamus/pathology","van den Bogaard, S. J.;Dumas, E. M.;Hart, E. P.;Milles, J.;Reilmann, R.;Stout, J. C.;Craufurd, D.;Gibbard, C. R.;Tabrizi, S. J.;van Buchem, M. A.;van der Grond, J.;Roos, R. A.",2013,Feb,10.3174/ajnr.A3303,0,
651,White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study,"BACKGROUND: Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. METHODS: This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. RESULTS: Severity of MTA differed between MCI subtypes (p<0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) CONCLUSION: We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.",Age Factors;Aged;Amnesia/*etiology/*pathology;Atrophy/etiology/pathology/psychology;Case-Control Studies;Cognition Disorders/etiology/*pathology/*psychology;Cohort Studies;Educational Status;Europe;Female;Humans;Male;Neuropsychological Tests;Sex Factors;Temporal Lobe/*pathology,"van de Pol, L. A.;Verhey, F.;Frisoni, G. B.;Tsolaki, M.;Papapostolou, P.;Nobili, F.;Wahlund, L. O.;Minthon, L.;Frolich, L.;Hampel, H.;Soininen, H.;Knol, D. L.;Barkhof, F.;Scheltens, P.;Visser, P. J.",2009,Oct,10.1136/jnnp.2008.158881,0,
652,Subtle blood-brain barrier leakage rate and spatial extent: Considerations for dynamic contrast-enhanced MRI: Considerations,"Purpose: Dynamic contrast-enhanced (DCE) MRI can be used to measure blood-brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE-MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored. Methods: Dual-time resolution DCE-MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki) and volume fraction of detectable leaking tissue (vL) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise-corrected histogram analysis of leakage maps. Computer simulations utilizing realistic Ki histograms, mimicking the strong effect of noise and variation in Ki values, were performed to understand the influence of scan time on the estimated leakage. Results: The mean Ki was very low (order of 10-4 min-1) and highly influenced by noise, causing the Ki to be increasingly overestimated at shorter scan times. In the white matter, the Ki was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, vL proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min. Conclusions: Several ways to improve the sensitivity of a DCE-MRI experiment to subtle BBB leakage were presented. We have provided vL as an attractive and potentially more time-efficient alternative to detect group differences in subtle and widespread blood-brain barrier leakage compared with leakage rate Ki. Recommendations on group size and scan time are made based on statistical power calculations to aid future research.",gadobutrol;aged;Alzheimer disease;article;blood brain barrier;brain cortex;clinical article;computer simulation;contrast to noise ratio;controlled study;dynamic contrast-enhanced magnetic resonance imaging;female;gray matter;hematocrit;human;male;nuclear magnetic resonance scanner;plasma volume;signal noise ratio;white matter;Achieva,"Van De Haar, H. J.;Jansen, J. F. A.;Jeukens, C. R. L. P. N.;Burgmans, S.;Van Buchem, M. A.;Muller, M.;Hofman, P. A. M.;Verhey, F. R. J.;Van Osch, M. J. P.;Backes, W. H.",2017,,10.1002/mp.12328,0,
653,Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease,"Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ((c))RSNA, 2016 Online supplemental material is available for this article.","0 (Contrast Media);Aged;Aged, 80 and over;Alzheimer Disease/ diagnostic imaging/ pathology;Blood Volume;Blood-Brain Barrier/ diagnostic imaging/ pathology;Case-Control Studies;Contrast Media;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Pilot Projects","van de Haar, H. J.;Burgmans, S.;Jansen, J. F.;van Osch, M. J.;van Buchem, M. A.;Muller, M.;Hofman, P. A.;Verhey, F. R.;Backes, W. H.",2016,Nov,,0,
654,Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease,"Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. (c)RSNA, 2016 Online supplemental material is available for this article.",,"van de Haar, H. J.;Burgmans, S.;Jansen, J. F.;van Osch, M. J.;van Buchem, M. A.;Muller, M.;Hofman, P. A.;Verhey, F. R.;Backes, W. H.",2016,May 31,10.1148/radiol.2016152244,0,653
655,Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates,"BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. METHODS: We evaluated CMIs on 3 Tesla MRI in a population-based cohort of 194 nondemented older people (72-80 years) with systolic hypertension. Using a case-control design, participants with and without CMIs were compared on age, sex, cardiovascular risk factors, and white matter hyperintensity volume. RESULTS: We identified 23 CMIs in 12 participants (6%). CMIs were associated with older age, higher diastolic blood pressure, and a history of recent stroke. There was a trend for a higher white matter hyperintensity volume in participants with CMIs. CONCLUSIONS: We found an association of CMIs with clinical parameters, including age and cardiovascular risk factors. Although the prevalence of CMIs is relatively low, our results suggest that the study of CMIs in larger clinical studies is possible using 3 Tesla MRI. This opens the possibility of large-scale prospective investigation of the clinical relevance of CMIs in older people.","Aged;Aged, 80 and over;Brain Infarction/ diagnosis;Cerebral Cortex/ pathology;Cohort Studies;Female;Humans;Magnetic Resonance Imaging;Male;White Matter/ pathology","van Dalen, J. W.;Scuric, E. E.;van Veluw, S. J.;Caan, M. W.;Nederveen, A. J.;Biessels, G. J.;van Gool, W. A.;Richard, E.",2015,Jan,10.1161/strokeaha.114.007568,0,
656,White matter hyperintensity volume and cerebral perfusion in older individuals with hypertension using arterial spin-labeling,"BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively.Wecompared white matter hyperintensity CBF, normal-appearing white matter CBF, andGMCBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized ==<0.248, P=.001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized==<0.065, P=.643) or GM CBF (standardized ==<0.035, P=.382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.",aged;arterial spin labeling;article;brain blood flow;brain perfusion;brain size;comparative study;female;human;major clinical study;male;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;radiological parameters;sensitivity analysis;systolic hypertension;white matter;white matter hyperintensity volume;Intera,"Van Dalen, J. W.;Mutsaerts, H. J. M. M.;Nederveen, A. J.;Vrenken, H.;Steenwijk, M. D.;Caan, M. W. A.;Majoie, C. B. L. M.;Van Gool, W. A.;Richard, E.",2016,,10.3174/ajnr.A4828,0,
657,White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling,"BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized beta = -0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized beta = -0.065, P = .643) or GM CBF (standardized beta = -0.035, P = .382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.",,"van Dalen, J. W.;Mutsaerts, H. J.;Nederveen, A. J.;Vrenken, H.;Steenwijk, M. D.;Caan, M. W.;Majoie, C. B.;van Gool, W. A.;Richard, E.",2016,Jun 9,10.3174/ajnr.A4828,0,
658,Effect of Long-Term Vascular Care on Progression of Cerebrovascular Lesions,"Background and Purpose - This study aimed to evaluate the effect of a nurse-led multidomain cardiovascular intervention on white matter hyperintensity (WMH) progression and incident lacunar infarcts in community-dwelling elderly with hypertension. Methods - The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. General practices were assigned by computer-generated randomization to 6-year nurse-led, multidomain intensive vascular care or standard care. Of 3526 preDIVA participants, 195 nondemented participants with a systolic blood pressure ≥140 mm Hg were consecutively recruited to undergo magnetic resonance imaging at 2 to 3 and 5 to 6 years after baseline. WMH volumes were measured automatically, lacunar infarcts assessed visually, blinded to treatment allocation. Results - One hundred and twenty-six participants were available for longitudinal analysis (64 intervention and 62 control). Annual WMH volume increase in milliliter was similar for intervention (mean=0.73, SD=0.84) and control (mean=0.70, SD=0.59) participants (adjusted mean difference, -0.08 mL; 95% confidence interval, -0.30 to 0.15; P=0.50). Analyses suggested greater intervention effects with increasing baseline WMH volumes (P for interaction=0.03). New lacunar infarcts developed in 6 (9%) intervention and 2 (3%) control participants (odds ratio, 2.2; 95% confidence interval, 0.4-12.1; P=0.36). Conclusions - Nurse-led vascular care in hypertensive community-dwelling older persons did not diminish WMH accumulation over 3 years. However, our results do suggest this type of intervention could be effective in persons with high WMH volumes. There was no effect on lacunar infarcts incidence but numbers were low.",aged;article;cerebrovascular disease;controlled study;dementia;disease course;female;human;hypertension;lacunar stroke;longitudinal study;major clinical study;male;neuroimaging;neurologic disease assessment;nuclear magnetic resonance imaging;priority journal;randomization;randomized controlled trial;systolic blood pressure;white matter;white matter lesion,"Van Dalen, J. W.;Moll Van Charante, E. P.;Caan, M. W. A.;Scheltens, P.;Majoie, C. B. L. M.;Nederveen, A. J.;Van Gool, W. A.;Richard, E.",2017,,10.1161/strokeaha.117.017207,0,
659,Neuropsychiatric symptoms of cholinergic deficiency occur with degradation of the projections from the nucleus basalis of Meynert,"This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosis.",Acetyl cholinesterase;Behavioral symptoms;Dementia;Neurodegeneration;Tractography;White matter;White matter hyperintensities,"van Dalen, J. W.;Caan, M. W. A.;van Gool, W. A.;Richard, E.",2017,Dec,,0,
660,Neuropsychiatric symptoms of cholinergic deficiency occur with degradation of the projections from the nucleus basalis of Meynert,"This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosis.",Acetyl cholinesterase;Behavioral symptoms;Dementia;Neurodegeneration;Tractography;White matter;White matter hyperintensities,"van Dalen, J. W.;Caan, M. W.;van Gool, W. A.;Richard, E.",2016,Oct 27,,0,
661,A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease,"In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntington's disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN(+ctx)). Histologically, QUIN(+ctx) were distinguished from QUIN(-ctx) animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula. Although both techniques are complementary, the quantitative character of DTI makes it possible to pick up subtle differences in tissue microstructure that are not identified with histology. DTI demonstrated differential changes of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the internal and external capsula, and within a subregion of the caudate putamen. It was suggested that FA increased due to a selective loss of the subcortical connections targeted by degenerative processes at the early stage of the disease, which might turn the striatum into a seemingly more organized structure. When tissue degeneration becomes more severe, FA decreased while AD, RD and MD increased.","Animals;Behavior, Animal/physiology;Diffusion Tensor Imaging/ methods;Disease Models, Animal;Female;Huntington Disease/ diagnosis/pathology/physiopathology;Motor Skills Disorders/diagnosis/pathology/physiopathology;Nerve Degeneration/diagnosis/pathology/physiopathology;Neuroimaging/ methods;Rats;Rats, Wistar","Van Camp, N.;Blockx, I.;Camon, L.;de Vera, N.;Verhoye, M.;Veraart, J.;Van Hecke, W.;Martinez, E.;Soria, G.;Sijbers, J.;Planas, A. M.;Van der Linden, A.",2012,May,10.1016/j.neurobiolaging.2010.07.001,0,
662,Alterations in white matter volume and integrity in obesity and type 2 diabetes,"Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se.","Brain/ diagnostic imaging;Diabetes Mellitus, Type 2/ diagnostic imaging;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Obesity/ diagnostic imaging;Organ Size;White Matter/ diagnostic imaging;Brain;Dti;Integrity;Obesity;Type 2 diabetes;Vbm;Volume;White matter","van Bloemendaal, L.;Ijzerman, R. G.;Ten Kulve, J. S.;Barkhof, F.;Diamant, M.;Veltman, D. J.;van Duinkerken, E.",2016,Jun,,0,663
663,Alterations in white matter volume and integrity in obesity and type 2 diabetes,"Type 2 diabetes mellitus (T2DM) is characterized by obesity, hyperglycemia and insulin resistance. Both T2DM and obesity are associated with cerebral complications, including an increased risk of cognitive impairment and dementia, however the underlying mechanisms are largely unknown. In the current study, we aimed to determine the relative contributions of obesity and the presence of T2DM to altered white matter structure. We used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to measure white matter integrity and volume in obese T2DM patients without micro- or macrovascular complications, age- gender- and BMI-matched normoglycemic obese subjects and age- and gender-matched normoglycemic lean subjects. We found that obese T2DM patients compared with lean subjects had lower axial diffusivity (in the right corticospinal tract, right inferior fronto-occipital tract, right superior longitudinal fasciculus and right forceps major) and reduced white matter volume (in the right inferior parietal lobe and the left external capsule region). In normoglycemic obese compared with lean subjects axial diffusivity as well as white matter volume tended to be reduced, whereas there were no significant differences between normoglycemic obese subjects and T2DM patients. Decreased white matter integrity and volume were univariately related to higher age, being male, higher BMI, HbA1C and fasting glucose and insulin levels. However, multivariate analyses demonstrated that only BMI was independently related to white matter integrity, and age, gender and BMI to white matter volume loss. Our data indicate that obese T2DM patients have reduced white matter integrity and volume, but that this is largely explained by BMI, rather than T2DM per se.",,"van Bloemendaal, L.;Ijzerman, R. G.;Ten Kulve, J. S.;Barkhof, F.;Diamant, M.;Veltman, D. J.;van Duinkerken, E.",2016,Jan 27,10.1007/s11011-016-9792-3,0,
664,Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional brain imaging studies of transgenic mouse models of Alzheimer's Disease,"Fluorodeoxyglucosepositron emission tomography (PET) studies find that persons with Alzheimer's disease have preferential reductions in posterior cingulate activity. Using fluorodeoxyglucose autoradiography, we found that transgenic mice overexpressing a mutant form of the human amyloid precursor protein have preferentially reduced activity in the same region, providing a potential brain imaging indicator of Alzheimer's disease in these animals. In this study, we considered the feasibility of using in vivo imaging techniques, such as PET, to detect this reduction despite their limitations in spatial resolution. Autoradiographic measurements of posterior cingulate activity were remeasured in the previously studied PDAPP transgenic and littermate control mice after the images were filtered to lower spatial resolutions. We continued to detect significantly lower cingulate activity in the transgenic mice when the images were blurred to 0.50 mm, failed to detect significantly abnormal activity when the images were blurred to 0.75 mm, and, indeed, found significantly higher activity when the images were blurred to 1.0 mm. Reversal in direction of the abnormality appears attributable to a previously observed truncation in the corpus callosum in PDAPP mice. With the possible exception of future in vivo imaging techniques that have a spatial resolution greater than or equal to 0.50 mm and high sensitivity, noninvasive functional brain imaging techniques like PET may not be suitable for detecting declines in regional activity in PDAPP mice. It remains possible that these imaging techniques will prove useful in transgenic mouse lines that do not exhibit the same morphological abnormalities in neighboring white matter regions.","Alzheimer Disease/ radionuclide imaging;Amyloid beta-Protein Precursor/ genetics;Animals;Autoradiography/ methods;Brain/ pathology;Brain Chemistry/physiology;Fluorodeoxyglucose F18;Gyrus Cinguli/ radionuclide imaging;Image Processing, Computer-Assisted;Mice;Mice, Transgenic;Radiopharmaceuticals;Tomography, Emission-Computed","Valla, J.;Chen, K.;Berndt, J. D.;Gonzalez-Lima, F.;Cherry, S. R.;Games, D.;Reiman, E. M.",2002,May,10.1006/nimg.2002.1080,0,
665,Clinical evaluation of a high-resolution (2.6-mm) positron emission tomography,"The intrinsic resolution of the Donner 600-crystal positron emission tomograph (PET 600) is 2.6 mm full width at half maximum (FWHM) in-plane and 6 mm FWHM axially. More than 100 patients with glioma, radiation necrosis, Alzheimer disease, or epilepsy have been studied with this system. Approximately 1 million events are acquired in 15 minutes, starting 1 hour after injection of 10 mCi (370 MBq) of fluorine-18-fluorodeoxyglucose. Normal structures as small as the superior colliculi and the external capsule have been resolved. Improved separation of the cortical ribbon from adjacent white matter has allowed more accurate determination of cortical metabolic rate. In two of 15 patients undergoing evaluation for recurrent glioma, the PET 600 images showed tumor uptake that was not apparent on a lower-resolution study. A high-activity orbiting transmission source with electronic collimation allows accurate, short-duration transmission measurements to be made after radiopharmaceutical administration. The anatomic detail seen on the transmission images can be used for reproducible patient positioning with an accuracy of 1-2 mm perpendicular to the image plane. These findings demonstrate the practicality and clinical effectiveness of high-resolution positron emission tomography.","Alzheimer Disease/radionuclide imaging;Brain/ radionuclide imaging;Brain Diseases/ radionuclide imaging;Brain Neoplasms/radionuclide imaging;Deoxyglucose/analogs & derivatives;Epilepsy, Temporal Lobe/radionuclide imaging;Fluorine Radioisotopes;Fluorodeoxyglucose F18;Glioma/radionuclide imaging;Humans;Necrosis;Radiation Injuries/radionuclide imaging;Tomography, Emission-Computed/ methods","Valk, P. E.;Jagust, W. J.;Derenzo, S. E.;Huesman, R. H.;Geyer, A. B.;Budinger, T. F.",1990,Sep,10.1148/radiology.176.3.2389037,0,
666,Lifespan mental activity predicts diminished rate of hippocampal atrophy,"OBJECTIVE: Epidemiological studies suggest that complex mental activity may reduce the risk for dementia, however an underlying mechanism remains unclear. Our objective was to determine whether individual differences in lifespan complex mental activity are linked to altered rates of hippocampal atrophy independent of global measures of neurodegeneration. METHODS: Thirty seven healthy older individuals had their complex mental activity levels estimated using the Lifetime of Experiences Questionnaire (LEQ) and completed serial MRI investigations at baseline and three years follow-up. Hippocampal volume and semi-automatic quantitation of whole brain volume (WBV) and white matter hyperintensities (WMHs) were compared at both time points. RESULTS: Higher LEQ scores were correlated with hippocampal volume independent of covariates at the three year follow-up stage (r = 0.43, p = 0.012). Moreover, those with higher LEQ scores experienced less hippocampal atrophy over the follow-up period (r = 0.41, p = 0.02). High LEQ individuals had less than half the hippocampal volume decline of low LEQ individuals in a multivariate analysis (F = 4.47, p = 0.042). No parallel changes were found in measures of WBV and WMHs. CONCLUSIONS: High level of complex mental activity across the lifespan was correlated with a reduced rate of hippocampal atrophy. This finding could not be explained by general differences in intracranial volume, larger hippocampi at baseline, presence of hypertensive disease, gender or low mood. Our results suggest that neuroprotection in medial temporal lobe may be one mechanism underlying the link between mental activity and lower rates of dementia observed in population-based studies. Additional studies are required to further explore this novel finding.",Aged;Atrophy;Cognition Disorders/prevention & control;Cohort Studies;Dementia/prevention & control;Hippocampus/*pathology;Humans;*Mental Processes,"Valenzuela, M. J.;Sachdev, P.;Wen, W.;Chen, X.;Brodaty, H.",2008,,10.1371/journal.pone.0002598,0,
667,White matter abnormality in cerebral atrophy: clinicoradiological correlations,The computed tomography (CT) scans in 1.6% of patients with cerebral atrophy showed the additional feature of areas of reduced attenuation in the deep cerebral white matter. Analysis of the clinical data showed a significant association with both hypertension and dementia. Etat crible in vascular hypertension is suggested as the possible cause.,"Adult;Aged;Atrophy;Brain Diseases/*radiography;Cerebral Cortex/*pathology;Cerebral Ventriculography;Dominance, Cerebral;Female;Hemodynamics;Humans;Hypertension/complications;Male;Middle Aged;Nervous System Diseases/etiology;Neurocognitive Disorders/etiology","Valentine, A. R.;Moseley, I. F.;Kendall, B. E.",1980,Feb,,0,
668,First report of a pathogenic mutation on exon 24 of the NOTCH3 gene in a CADASIL family,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted small vessel disease clinically characterized by migraine, recurrent subcortical strokes, and cognitive and mood disorders. Pathogenic mutations are located on any of the exons of the NOTCH3 gene coding for epidermal-growth factor (EGF)-like repeats of the extracellular domain of the NOTCH3 receptor. Because the gene is large and the mutations cluster on some exons, many laboratories restrict the analysis to these exons. We report the first missense mutation involving exon 24 and causing CADASIL in a 64-year-old man. The patient was admitted to the hospital for a loss of consciousness accompanied by profuse sweating. On examination, some parkinsonian features were present. Over the last 4 years, he had developed postural instability and gait disturbances with repeated falls, behavioral disorders, and cognitive impairment. A diagnostic hypothesis of atypical parkinsonism had been advanced. The presence of multiple subcortical lacunar infarcts and leukoencephalopathy extended to the external capsule on cerebral MRI suggested the presence of CADASIL. The diagnosis was confirmed by finding a heterozygous mutation leading to a cysteine substitution on exon 24 of the NOTCH3 gene. One proband's brother, who had progressive gait disturbances, unilateral action tremor and bradykinesia, and an asymptomatic niece also resulted affected. This report underlines that when CADASIL is suspected the genetic analysis should be performed on all the NOTCH3 exons coding for EGF-like repeats including exon 24 and confirms that CADASIL may have heterogeneous phenotypes. © 2011 Springer-Verlag.",genomic DNA;levodopa;Notch3 receptor;quetiapine;adult;article;behavior disorder;bradykinesia;brain damage;brain infarction;CADASIL;case report;clinical examination;cognitive defect;computer assisted tomography;consciousness disorder;DNA extraction;electrocardiogram;electroencephalogram;exon;falling;gait disorder;gene mutation;genetic analysis;genetic screening;heterozygosity;hospital admission;human;irritability;laboratory test;lacunar infarct;leukoencephalopathy;male;memory disorder;missense mutation;neurologic examination;nuclear magnetic resonance imaging;orthostatic hypotension;parkinsonism;pathogenesis;priority journal;single photon emission computer tomography;sweating;tremor;white matter,"Valenti, R.;Bianchi, S.;Pescini, F.;D'Eramo, C.;Inzitari, D.;Dotti, M. T.;Pantoni, L.",2011,,,0,
669,Clinicoradiological comparison between vascular parkinsonism and Parkinson's disease,"OBJECTIVE: To compare the clinical and radiological features of vascular parkinsonism (VP) and Parkinson's disease (PD). METHODS: Cross-sectional study where 15 patients with VP (8 (53.3%) men; aged 75.7 +/- 10.4 years) and 30 patients with PD (17 (56.7%) men; aged 67.3 +/- 7.5 years) underwent motor and cognitive evaluation and brain MRI. RESULTS: Patients with VP were, on average, 8.4 years older (p = 0.004); all had arterial hypertension. They presented with a sudden onset of parkinsonism (80%) and a rapidly progressive clinical course (53.3%). Predominant lower body parkinsonism (p<0.001), postural instability (p=0.003) with freezing of gait (p<0.001) and falls (p<0.001), urinary incontinence (p < 0.001) and pyramidal signs (p<0.001) were more common in patients with VP. Movement Disorders Society's Unified PD Rating Scale (MDS-UPDRS) scores were higher in patients with VP (p=0.005 in 'OFF' state and p<0.001 in 'ON' state). They had greater cognitive impairment and 12 (80%) fulfilled diagnostic criteria for probable vascular dementia. Most patients with VP had brain MRI changes: multiple lacunar infarcts (66.7%) or extensive white matter disease (26.7%). CONCLUSIONS: VP can be clinically distinguished from PD based on sudden onset of parkinsonism at an older age, characterised by lower body predominance, urinary incontinence, pyramidal signs, postural instability with freezing of gait and falls, and dementia.","Aged;Aged, 80 and over;Brain/pathology/physiopathology/radiography;Cross-Sectional Studies;Female;Humans;Magnetic Resonance Imaging;Male;Neuroimaging;Parkinson Disease/*diagnosis/pathology/physiopathology/*radiography;Parkinson Disease, Secondary/*diagnosis/pathology/physiopathology/*radiography;Symptom Assessment;Cerebrovascular Disease;Clinical Neurology;Gait;Parkinson's Disease;Vascular Dementia","Vale, T. C.;Caramelli, P.;Cardoso, F.",2015,May,10.1136/jnnp-2014-307867,0,670
670,Clinicoradiological comparison between vascular parkinsonism and Parkinson's disease,"Objective To compare the clinical and radiological features of vascular parkinsonism (VP) and Parkinson's disease (PD). Methods Cross-sectional study where 15 patients with VP (8 (53.3%) men; aged 75.7±10.4 years) and 30 patients with PD (17 (56.7%) men; aged 67.3±7.5 years) underwent motor and cognitive evaluation and brain MRI. Results Patients with VP were, on average, 8.4 years older (p=0.004); all had arterial hypertension. They presented with a sudden onset of parkinsonism (80%) and a rapidly progressive clinical course (53.3%). Predominant lower body parkinsonism (p<0.001), postural instability (p=0.003) with freezing of gait (p<0.001) and falls (p<0.001), urinary incontinence (p<0.001) and pyramidal signs (p<0.001) were more common in patients with VP. Movement Disorders Society's Unified PD Rating Scale (MDS-UPDRS) scores were higher in patients with VP (p=0.005 in 'OFF' state and p<0.001 in 'ON' state). They had greater cognitive impairment and 12 (80%) fulfilled diagnostic criteria for probable vascular dementia. Most patients with VP had brain MRI changes: multiple lacunar infarcts (66.7%) or extensive white matter disease (26.7%). Conclusions VP can be clinically distinguished from PD based on sudden onset of parkinsonism at an older age, characterised by lower body predominance, urinary incontinence, pyramidal signs, postural instability with freezing of gait and falls, and dementia. © 2014 by the BMJ Publishing Group Ltd.",parkinsonism;Parkinson disease;human;patient;gait;brain;pyramidal sign;urine incontinence;freezing;male;Unified Parkinson Disease Rating Scale;multiinfarct dementia;diagnosis;cognitive defect;cross-sectional study;nuclear magnetic resonance imaging;society;disease course;dementia;motor dysfunction;hypertension;white matter;infarction;publishing,"Vale, T. C.;Caramelli, P.;Cardoso, F.",2014,,10.1136/jnnp-2014-307867,0,
671,Close correlation between quantitative and qualitative assessments of white matter lesions,"Background: White matter lesions (WML) increase with age and are associated with stroke, cognitive decline and dementia. They can be visually rated or computationally assessed. Methods: We compared WML Fazekas visual rating scores and volumes, determined using a validated multispectral image-fusion technique, in Magnetic Resonance Imaging from 672 participants of the Lothian Birth Cohort 1936 and sought explanations for subjects in whom the correlation (Spearman's ρ) between the total Fazekas score (summed deep and periventricular ratings, 0-6) and WML volume did not concur (z-score difference >1). Infarcts were identified separately. Results: The median WML Fazekas score was 2 [inter-quartile range (IQR): 2], median WML volume 7.7 ml (IQR: 13.6 ml) and median infarct volume (n = 95) 0.98 ml. Score and volume were highly correlated (Spearman's ρ = 0.78, p < 0.001). Infarcts did not alter the correlation. Minor discordance occurred in 94/672 (14%) subjects, most with total Fazekas score of 1 (n = 20, WML volume = 4.5-14.8 ml) or 2 (n = 50, WML volume = 0.1-34.4 ml). The main reasons were: subtle WML identified visually but omitted from the volume; prominent ventricular caps but thin body lining giving a periventricular score of 1/2 but large WML volume, and small deep focal lesions which increase the score disproportionally when beginning to coalesce with little change in WML volume. Conclusions: WML rating scores and volumes provide near-equivalent estimates of WML burden, therefore either can be used depending on research circumstances. Even closer agreement could result from improved computational detection of subtle WML and modified visual ratings to differentiate prominent ventricular caps from thin periventricular linings, and small non-coalescent from early coalescent deep WML. Copyright © 2012 S. Karger AG, Basel.",,"Valdés Hernández, M. D. C.;Morris, Z.;Dickie, D. A.;Royle, N. A.;Muñoz Maniega, S.;Aribisala, B. S.;Bastin, M. E.;Deary, I. J.;Wardlaw, J. M.",2013,December,,0,
672,Brain white matter damage in aging and cognitive ability in youth and older age,"Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β=-0.14, p < 0.01) and processing speed (β=-0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β=-0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging. © 2013 The Authors.",,"Valdés Hernández, M. D. C.;Booth, T.;Murray, C.;Gow, A. J.;Penke, L.;Morris, Z.;Maniega, S. M.;Royle, N. A.;Aribisala, B. S.;Bastin, M. E.;Starr, J. M.;Deary, I. J.;Wardlaw, J. M.",2013,December,,0,
673,"Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke","Rationale: Cerebral small vessel disease (SVD) is common in ageing and patients with dementia and stroke. Its manifestations on magnetic resonance imaging (MRI) include white matter hyperintensities, lacunes, microbleeds, perivascular spaces, small subcortical infarcts, and brain atrophy. Many studies focus only on one of these manifestations. A protocol for the differential assessment of all these features is, therefore, needed. Aims: To identify ways of quantifying imaging markers in research of patients with SVD and operationalize the recommendations from the STandards for ReportIng Vascular changes on nEuroimaging guidelines. Here, we report the rationale, design, and methodology of a brain image analysis protocol based on our experience from observational longitudinal studies of patients with nondisabling stroke. Design: The MRI analysis protocol is designed to provide quantitative and qualitative measures of disease evolution including: acute and old stroke lesions, lacunes, tissue loss due to stroke, perivascular spaces, microbleeds, macrohemorrhages, iron deposition in basal ganglia, substantia nigra and brain stem, brain atrophy, and white matter hyperintensities, with the latter separated into intense and less intense. Quantitative measures of tissue integrity such as diffusion fractional anisotropy, mean diffusivity, and the longitudinal relaxation time are assessed in regions of interest manually placed in anatomically and functionally relevant locations, and in others derived from feature extraction pipelines and tissue segmentation methods. Morphological changes that relate to cognitive deficits after stroke, analyzed through shape models of subcortical structures, complete the multiparametric image analysis protocol. Outcomes: Final outcomes include guidance for identifying ways to minimize bias and confounds in the assessment of SVD and stroke imaging biomarkers. It is intended that this information will inform the design of studies to examine the underlying pathophysiology of SVD and stroke, and to provide reliable, quantitative outcomes in trials of new therapies and preventative strategies.",,"Valdés Hernández, M. D. C.;Armitage, P. A.;Thrippleton, M. J.;Chappell, F.;Sandeman, E.;Muñoz Maniega, S.;Shuler, K.;Wardlaw, J. M.",2015,1,,0,
674,"Morphologic, distributional, volumetric,and intensity characterization of periventricular hyperintensities","BACKGROUND AND PURPOSE: White matter hyperintensities are characteristic of old age and identifiable on FLAIR and T2-weighted MR imaging. They are typically separated into periventricular or deep categories. It is unclear whether the innermost segment of periventricular white matter hyperintensities is truly abnormal or is imaging artifacts. MATERIALS AND METHODS: We used FLAIR MR imaging from 665 community-dwelling subjects 72-73 years of age without dementia. Periventricular white matter hyperintensities were visually allocated into 4 categories: 1) thin white line; 2) thick rim; 3) penetrating toward or confluent with deep white matter hyperintensities; and 4) diffuse ill-defined, labeled as ""subtle extended periventricular white matter hyperintensities."" We measured the maximum intensity and width of the periventricular white matter hyperintensities, mapped all white matter hyperintensities in 3D, and investigated associations between each category and hypertension, stroke, diabetes, hypercholesterolemia, cardiovascular disease, and total white matter hyperintensity volume. RESULTS: The intensity patterns and morphologic features were different for each periventricular white matter hyperintensity category. Both the widths (r = 0.61, P < .001) and intensities (r = 0.51, P < .001) correlated with total white matter hyperintensity volume and with each other (r = 0.55, P < .001) for all categories with the exception of subtle extended periventricular white matter hyperintensities, largely characterized by evidence of erratic, ill-defined, and fragmented pale white matter hyperintensities (width: r = 0.02, P = .11; intensity: r = 0.02, P = .84). The prevalence of hypertension, hypercholesterolemia, and neuroradiologic evidence of stroke increased from periventricular white matter hyperintensity categories 1 to 3. The mean periventricular white matter hyperintensity width was significantly larger in subjects with hypertension (mean difference = 0.5 mm, P = .029) or evidence of stroke (mean difference = 1 mm, P < .001). 3D mapping revealed that periventricular white matter hyperintensities were discontinuous with deep white matter hyperintensities in all categories, except only in particular regions in brains with category 3. CONCLUSIONS: Periventricular white matter hyperintensity intensity levels, distribution, and association with risk factors and disease suggest that in old age, these are true tissue abnormalities and therefore should not be dismissed as artifacts. Dichotomizing periventricular and deep white matter hyperintensities by continuity from the ventricle edge toward the deep white matter is possible.",,"Valdés Hernández, M. C.;Piper, R. J.;Bastin, M. E.;Royle, N. A.;Muñoz Maniega, S.;Aribisala, B. S.;Murray, C.;Deary, I. J.;Wardlaw, J. M.",2014,January,,0,
675,Computed tomography in neuronal ceroid lipofuscinosis,"The computed tomography (CT) findings in a verified case of neuronal ceroid lipofuscinosis (NCL) are presented. CT revealed diffuse and severe cerebral atrophy, reflected by generalized subarachnoid space enlargement and symmetric ventricular dilatation. There was no evidence of abnormalities of the white matter. The CT features in our case of NCL correspond perfectly with the neuropathologic changes of the disease mentioned in the literature. Furthermore, CT is of considerable help in differentiating between those inherited metabolic brain diseases characterized primarily by white matter involvement and those presenting predominantly with changes of grey matter.",case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;metabolic encephalopathy;neuronal ceroid lipofuscinosis;preschool child,"Valavanis, A.;Friede, R. L.;Schubiger, O.;Hayek, J.",1980,,,0,
676,Migraine with aura and brain magnetic resonance imaging abnormalities in patients with CADASIL,"BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of brain magnetic resonance signal abnormalities between cases and controls. SETTING: Patients with CADASIL seen at Lariboisiere Hospital. PATIENTS: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.","Adult;Aged;Brain/ pathology;Chi-Square Distribution;Dementia, Multi-Infarct/complications/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Migraine with Aura/complications/ pathology;Prospective Studies","Vahedi, K.;Chabriat, H.;Levy, C.;Joutel, A.;Tournier-Lasserve, E.;Bousser, M. G.",2004,Aug,10.1001/archneur.61.8.1237,0,
677,Clinical and brain MRI follow-up study of a family with COL4A1 mutation,"OBJECTIVE: To better delineate the clinical spectrum and the natural history of COL4A1 mutations, a newly defined genetic cause of small vessel disease including the brain and retina. METHODS: Clinical and brain MRI follow-up study of a family with COL4A1 mutation. RESULTS: During a 7-year period, two affected members died from intracranial hemorrhage. Four other members had a COL4A1 mutation (age ranges 25 to 74 years). None reported stroke or retinal hemorrhage or hematuria and none had dementia according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Follow-up brain MRI showed grade 3 diffuse leukoencephalopathy in three out of four patients. All had dilated perivascular spaces and three out of four had silent microbleeds mainly in the deep white matter. MRI signal abnormalities did not change in severity, number, or location between baseline and follow-up imaging. CONCLUSIONS: COL4A1 mutation carriers have great diversity in the clinical expression of the disease within the same family. Some affected family members may remain asymptomatic during several years of follow-up and have no evidence of progression of vascular changes on brain MRI. ©2007AAN Enterprises, Inc.",,"Vahedi, K.;Boukobza, M.;Massin, P.;Gould, D. B.;Tournier-Lasserve, E.;Bousser, M. G.",2007,October,,0,
678,Study on clinical spectrum of vascular cognitive impairment,Introduction: Vascular dementia is the second most common cause of dementia comprising about 1/3 of all dementia. In India we have increased incidence of stroke and high number of cardiovascular disease burden which have contributed to increasing number of patients with VCI. Aim: To study the clinical spectrum of vascular cognitive impairment. Objectives: To determine the risk factors for VCI To analyze the clinical spectrum and cognitive profiles in VCI Material and Methods: This is a prospective analytic study. 50 Vascular dementia patients fulfilling NINDS - AIREN criteria (probable and possible) were studied for one year (Sep 13 - Aug 14) at Institute of Neurology Chennai. The clinical spectrum of VCI was assessed by MRI and clinical profile. Cognitive functions were assessed by MOCA Addenbrookes test. The significance of score was obtained by using ANOVA test and post HOC test. Results: The risk factors of VCI such as age sex education duration DM SHT dyslipidemia Coronary artery disease atrial fibrillation smoking alcohol were analyzed by chi square and found that all are clinically and statistically significant. This spectrum is broadly classified into large vessel disease (42%) small vessel disease (32%) strategic infarct (10%) dementia due to intracerebral hemorrhage (8%) and minimal cognitive impairment (8%). The executive functions Visuospatial fluency attention memory are most commonly affected in vascular dementia. Conclusion: In our study hypertension diabetes and CAD stays an important risk factor for VCI. In the spectrum of VCI the most common disorder was found to be large vessel disease(42% ) followed by small vessel disease (32%) strategic infarct (10%) hemorrhagic dementia (8%) and MCI (8%). The executive functions are most commonly affected in vascular dementia compared to other dementia.,cognitive defect;Indian;neurology;dementia;multiinfarct dementia;risk factor;executive function;infarction;human;patient;cardiovascular disease;cerebrovascular accident;atrial fibrillation;smoking;India;coronary artery disease;dyslipidemia;diseases;diabetes mellitus;hypertension;memory;sexual education;brain hemorrhage;cognition;analysis of variance;nuclear magnetic resonance imaging;post hoc analysis;alcohol,"Vadivel, S.;Bhanu, K.",2015,,,0,
679,Diagnosis of affection of small cerebral vessels using coloured transcranial sonography by evaluation of the resistance index,"Affection of small cerebral vessels participate in serious diseases such as lacunar infractions and subcortical vascular dementia. In coloured transcranial duplex sonography for evaluation of vascular resistance Pourcelot's resistance index (RI) is used. The authors tried to find out whether it is possible to use RI in the diagnosis of affections of small cerebral vessels (small vessel disease) and find a borderline between pathological and normal findings. Transcranial coloured coded duplex sonography (TCCS) was used in 45 patients hospitalized on account of acute ischaemic cerebral attacks and who had clinical or radilogical (CT, MRI) signs of affection of arterioles. Among clinical signs they included: patients with the clinical picture of lacunar infractions, vascular extrapyramidal syndrome signs of subcortical vascular dementia and quadrispastic syndrome. Among CT or MRI signs the authors included: signs of leukoaraiosis, multiple bilateral capsular infractions, subcortical infractions, lacunar infractions in the brainstem. On an HDI ATL 3000 apparatus by means of a linear probe 5-10 MHz a duplex examination of extracranial vessels was made followed by transcranial examination on the same apparatus by a sector probe 2-3 MHz. Flow rates in both middle cerebral arteries (MCA) (n = 80) were assessed: peak systolic velocity (PSV), enddiastolic velocity and Pourcelot's resistance index. The assessed values were compared with a control sample of the same number MCAs (n = 80) in subjects without cerebrovascular disease. In the group of patients the following values were obtained: PSV = 80 cm/s, EDV = 28 cm/s, RI = 0.65; in the control group: PSV = 90 cm/s, EDV = 38 cm/s, RI = 0.58. The values in the two groups were compared using the non-paired Student t-test. For PSV p < 0.001, for EDV p < 0.0001, for RI p < 0.001. The cut off point was RI = 0.62 with 70 % sensitivity and 80 % specificity. The study provided evidence of a higher RI with lower PSV and EDV in the group of patients with signs of small vessels disease as compared with the control group. In the authors opinion RI proved as an auxiliairy diagnostic tool for assessment of affections of the small cerebral vessels.",arteriole;artery blood flow;article;blood flow velocity;brain blood vessel;brain infarction;brain stem infarction;cerebrovascular accident;cerebrovascular disease;clinical article;clinical examination;clinical feature;computer assisted tomography;controlled study;diagnostic value;Doppler echography;extrapyramidal syndrome;hospital admission;human;leukoaraiosis;multiinfarct dementia;nuclear magnetic resonance imaging;sensitivity and specificity;Student t test;symptomatology;systole;vascular disease;vascular resistance;HDI ATL 3000,"Václavík, D.;Školoudík, D.",2004,,,0,
680,The R110C mutation in Notch3 causes variable clinical features in two Turkish families with CADASIL syndrome,"Mutations in Notch3 gene are responsible for the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). It is a late onset neurological disorder recognized by recurrent strokes and dementia. We describe here the clinical and molecular findings of three unrelated Turkish families with CADASIL syndrome. Two of the families were identified to have the same mutation, p.R110C (c.C328T), located in exon 3 of the Notch3 gene. Interestingly, the phenotypic expression of the disease in these two families was markedly different in severity and age of onset implicating additional genetic and/or non-genetic modulating factors involved in the pathogenesis. In addition, we identified the novel p.C201R (c.T601C) mutation in exon 4 of the Notch3 gene in a proband of the third family with two consecutive stroke-like episodes and typical MRI findings. Mutations described here cause an odd number of cysteines in the N-terminal of the EGF domain of Notch3 protein, which seems to have an important functional effect in the pathophysiology of CADASIL. The phenotypic variability in families carrying the same molecular defect as presented here makes the prediction of prognosis inconceivable. Although DNA analysis is effective and valuable in diagnosing approximately 90% of the CADASIL patients, lack of genotype-phenotype correlation and prognostic parameters makes the presymptomatic genetic counseling very difficult. © 2006 Elsevier B.V. All rights reserved.",cysteine;Notch3 receptor;adult;amino terminal sequence;article;CADASIL;clinical article;clinical feature;exon;family;gene expression;gene identification;gene mutation;human;nuclear magnetic resonance imaging;pathophysiology;phenotype;priority journal;cerebrovascular accident;Turkey (republic),"Uyguner, Z. O.;Siva, A.;Kayserili, H.;Saip, S.;Altýntath, A.;Apak, M. Y.;Albayram, S.;Ithýk, N.;Akman-Demir, G.;Taoyürekli, M.;Öz, B.;Wollnik, B.",2006,,,0,
681,Arg133Cys mutation of Notch3 in two unrelated Japanese families with CADASIL,"OBJECTIVE: More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of CADASIL in Orientals, we investigated Japanese families presenting as CADASIL. METHODS: We performed the PCR-SSCP and sequence analyses using genomic DNA, isolated from venous blood of participants under informed consent. PATIENTS: We identified two unrelated Japanese families with CADASIL, including 5 affected members through 2 generations. RESULTS: Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM) within the basal lamina of pericytes in muscular capillaries. On PCR-SSCP and sequence analyses, a heterozygous Arg133Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for CADASIL mutations in Caucasian families. None of the non-affected members nor the 50 Japanese normal controls revealed this mutation. CONCLUSION: Thus, our results confirm that CADASIL is a geographically widespread disorder caused by a Notch3 mutation.","arginine;cell surface receptor;cystine;Notch receptor;NOTCH3 protein, human;oncoprotein;primer DNA;article;brain;case report;chemistry;DNA sequence;ethnology;female;genetics;human;Japan;male;middle aged;multiinfarct dementia;nuclear magnetic resonance imaging;nucleotide sequence;pathology;pedigree;point mutation;polymerase chain reaction;single strand conformation polymorphism","Uyama, E.;Tokunaga, M.;Suenaga, A.;Kotorii, S.;Kamimura, K.;Takahashi, K.;Tabira, T.;Uchino, M.",2000,,,0,682
682,Arg133Cys mutation of Notch3 in two unrelated Japanese families with CADASIL,"OBJECTIVE: More than 80 unrelated, but all Caucasian, patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), originating from various communities around the world, have been molecularly identified. To clarify the occurrence of CADASIL in Orientals, we investigated Japanese families presenting as CADASIL. METHODS: We performed the PCR-SSCP and sequence analyses using genomic DNA, isolated from venous blood of participants under informed consent. PATIENTS: We identified two unrelated Japanese families with CADASIL, including 5 affected members through 2 generations. RESULTS: Each of the affected individuals developed recurrent strokes without risk factors resulting in progressive dementia, pseudobulbar palsy, and gait disturbances which started after the fifth decade of life. Although affected individuals had no vascular risk factors, they showed various degrees of narrowing of retinal arteries. Their MRI/CTs showed characteristics of the disease; bilateral small infarcts in the thalamus, basal ganglia, brain stem, and deep white matter in addition to the findings of leukoaraiosis. On SPECT imaging, there was severe hypoperfusion in the cortex as well as in the white matter. Ultrastructural studies revealed an abnormal deposition of granular osmiophilic materials (GOM) within the basal lamina of pericytes in muscular capillaries. On PCR-SSCP and sequence analyses, a heterozygous Arg133Cys mutation was present, in the affected individuals, in the exon 4 of Notch3 gene which is the hot spot region for CADASIL mutations in Caucasian families. None of the non-affected members nor the 50 Japanese normal controls revealed this mutation. CONCLUSION: Thus, our results confirm that CADASIL is a geographically widespread disorder caused by a Notch3 mutation.",,"Uyama, E.;Tokunaga, M.;Suenaga, A.;Kotorii, S.;Kamimura, K.;Takahashi, K.;Tabira, T.;Uchino, M.",2000,Sep,,0,
683,"Dentatorubral-pallidoluysian atrophy (DRPLA): Clinical, genetic, and neuroradiologic studies in a family","The clinical, genetic, and neuroradiologic characteristics of dentatorubral-pallidoluysian atrophy (DRPLA) are delineated in six patients from three generations of a Japanese family. The clinical characteristics of the disease varied, the age at onset depending on patients with juvenile-onset were characterized by myoclonus, epilepsy, and mental retardation whereas cerebellar ataxia, choreoathetosis, and dementia were typical of adult- and senile-onset patients. All affected individuals showed one expanded allele with the repeat number of CAG at the DRPLA locus, ranging from 58 to 82, and a normal allele, ranging from 10 to 21. The most severely affected patient, a case of maternal transmission and with the largest allele, became bedridden in a vegetative state by age 12. On the CT and MRI, varying degrees of brain atrophy were present in all patients. T2-weighted MRI in patients with senile-onset showed symmetric high-signal lesions in the cerebral white matter, globus pallidus, thalamus, midbrain, and pons. However, MRI in younger patients revealed no such lesions and CT failed to demonstrate lesions in the globus pallidus and brain stem. Thus, intrafamilial heterogeneity of DRPLA was also evident on MRI. High-signal lesions involving both, subcortical white matter and thalamus may be characteristics of senile-onset patients and may correlate with their dementia.",adolescent;adult;aged;article;brain atrophy;clinical article;controlled study;dementia;DNA determination;female;human;male;myoclonus;nuclear magnetic resonance;polymerase chain reaction;priority journal;school child;thalamus,"Uyama, E.;Kondo, I.;Uchino, M.;Fukushima, T.;Murayama, N.;Kuwano, A.;Inokuchi, N.;Ohtani, Y.;Ando, M.",1995,,,0,
684,Presenile-onset cerebral adrenoleukodystrophy presenting as Balint's syndrome and dementia,"We describe a patient with presenile-onset cerebral adrenoleukodystrophy presenting as Balint's syndrome and dementia. There were demyelinating MRI changes in the parieto-occipital white matter bilaterally, including the splenium of the corpus callosum. Therapeutic trials using 1-deamino-(8-D- arginine)-vasopressin, very long-chain fatty acid-free diet, and γ-globulin were of no benefit.",desmopressin;immunoglobulin;very long chain fatty acid;adrenoleukodystrophy;adult;article;case report;clinical feature;dementia;diet therapy;human;lipid diet;male;nuclear magnetic resonance imaging;priority journal,"Uyama, E.;Iwagoe, H.;Maeda, J.;Nakamura, M.;Terasaki, T.;Ando, M.",1993,,,0,
685,A case of steroid-responsive encephalopathy with positive 14-3-3 protein of the cerebrospinal fluid clinically resembling Creutzfelt-Jakob disease,"A 69-year old man developed subacutely progressive dementia, inactivity, and gait disturbance. On admission, he showed flutter-like oscillation of the bilateral eyes and myoclonus with upper extremities. Cerebrospinal fluid (CSF) analysis revealed elevation of protein (73.2mg/dl) and the positive 14-3-3 protein. An electroencephalogram (EEG) revealed diffuse slowing (2-3Hz, 80μ V). Brain MRI showed high intensity lesions in the white matter and left thalamus on FLAIR and diffusion imaging. We first suspected Creutzfelt-Jakob disease (CJD), but his symptoms didn't progress and showed no PSD on EEG. Oral corticosteroid therapy (prednisolone 60mg/day) brought him remarkable recovery corresponding with improvement of CSF and EEG findings. Despite of etiology unknown, we made a diagnosis of steroid-responsive encephalopathy.",,"Utsumiya, K.;Arakawa, R.;Fujimoto, S.;Ueyama, H.;Kumamoto, T.",2004,September,,0,
686,CADASIL syndrome in a large Turkish kindred caused by the R90C mutation in the Notch3 receptor,"Mutations in the Notch3 gene are the cause of the autosomal dominant disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). The CADASIL is an adult-onset neurologic disorder (average age of onset is 45 years) characterized by recurrent strokes and dementia. Clinical features combined with cerebral magnetic resonance imaging (MRI), showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter, are highly contributive to the diagnosis. We present a Turkish family with CADASIL, in which 12 individuals in four generations were affected showing the typical clinical features of recurrent strokes. Mutation analysis of the Notch3 receptor gene identified the recently described R90C mutation in the N-terminal part of the gene in affected individuals. Interestingly, migraine without aura was found as an initial symptom of the disease in two young mutation carriers (22 and 25 years, respectively), who did not show any additional clinical features or any MRI abnormalities. This indicates that migraine without aura in the absence of MRI abnormalities may represent an early initial symptom of CADASIL, which is difficult to diagnose in the absence of molecular diagnosis. Therefore, the used molecular screening method for Notch3 mutations provides a rapid and accurate diagnostic tool in addition to the standard diagnostic procedures.",,"Utku, U.;Celik, Y.;Uyguner, O.;Yüksel-Apak, M.;Wollnik, B.",2002,2002,,0,
687,"Autosomal dominant early onset dementia and leukoencephalopathy in a Japanese family: Clinical, neuroimaging and genetic studies","We report here the results of clinical, neuroimaging and genetic studies of autosomal dominant dementia and leukoencephalopathy in a Japanese family. Twenty-two individuals in this family were examined clinically (17 living, 5 deceased), neuroradiologically and genetically (16 of 17 living members). Ten (5 deceased) of 22 individuals had early onset dementia (age of onset: 45.2 ± 12.1 years on average) and four of them had multiple white matter lesions and brain atrophy on brain MRI without history of brain ischemic attack. Another four individuals had abnormal white matter lesions on brain MRI without dementia. Linkage studies for chromosome 1q31-42, 14q24.3 and 21q21 responsible for Alzheimer's disease, chromosome 19p13.1-13.2 for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and chromosome 3 for familial non-specific dementia suggested no specific haplotypes cosegregated with the disease. Apo E genotypes were E2/2 and E2/3 in this family. Clinical, neuroimaging and genetic studies revealed that the disease in this family was distinguished from known familial dementia. This is the first report of a large Japanese family with autosomal dominant early onset dementia and leukoencephalopathy.",adult;aged;Alzheimer disease;article;chromosome 1;chromosome 14;chromosome 19;chromosome 21;chromosome 3;clinical article;controlled study;dementia;female;gene locus;human;leukoencephalopathy;male;nuclear magnetic resonance imaging;priority journal,"Utatsu, Y.;Takashima, H.;Michizono, K.;Kanda, N.;Endou, K.;Mitsuyama, Y.;Fujimoto, T.;Nagai, M.;Umehara, F.;Higuchi, I.;Arimura, K.;Nakagawa, M.;Osame, M.",1997,,,0,
688,Autopsy-Proven Intravascular Lymphoma Presenting as Rapidly Recurrent Strokes,"We present a 79-year-old Japanese woman diagnosed with cerebral infarction. In spite of enough antiplatelet and anticoagulant therapy, she presented rapidly recurrent strokes three times for 3 months. Magnetic resonance imaging showed progression of bilateral cerebral infarcts, and chest-abdominal computed tomography showed multiple bilateral nodular lesions in the lung and multiple tumor lesions in the liver. Autopsy revealed diagnosis of intravascular lymphoma (IVL). This case indicates that IVL is rare and usually goes undiagnosed until time of autopsy because of its protean neurological manifestations; hence, it should be considered as a possible etiology if multiple strokes occur in a short period of time.",acetylsalicylic acid;alkaline phosphatase;antibiotic agent;argatroban;C reactive protein;calcium;gamma glutamyltransferase;glucose;hemoglobin A1c;heparin;lactate dehydrogenase;phosphorus;soluble interleukin 2 receptor;ticlopidine;warfarin;abdominal radiography;aged;anemia;anterior cerebral artery;anticoagulant therapy;arteriosclerosis;article;autopsy;brain infarction;brain ischemia;case report;cerebrovascular accident;cholecystitis;cholesterol blood level;computer assisted tomography;disease course;dyslipidemia;electrocardiography;female;gait disorder;glucose blood level;human;hypoalbuminemia;internal carotid artery;Japanese (people);lacunar stroke;large cell lymphoma;liver tumor;lung nodule;lymphoid cell;magnetic resonance angiography;mental deterioration;middle cerebral artery;multiple organ failure;muscle weakness;neuroimaging;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;priority journal;thorax radiography;tumor embolism;unconsciousness,"Usuda, D.;Arahata, M.;Temaru, R.;Iinuma, Y.;Kanda, T.;Hayashi, S.",2016,,10.1159/000444632,0,
689,High-signal-intensity abnormalities evaluated by 3D fluid-attenuated inversion recovery imaging within the drainage territory of developmental venous anomalies identified by susceptibility-weighted imaging at 3 T,"Purpose: To evaluate brain parenchymal high-signal-intensity abnormalities within the drainage territory of developmental venous anomalies (DVAs) identified by susceptibility-weighted imaging (SWI) at 3 T. Methods: One hundred and thirty patients with 137 DVAs identified by SWI were retrospectively studied. 3D fluid-attenuated inversion recovery (FLAIR) images were reviewed for parenchymal high-signal-intensity abnormalities and SWI images were reviewed for hypointense foci (microhemorrhages or cavernous malformations) adjacent to DVAs. Patient age, the degree of underlying white matter disease, DVA location (supratentorial or infratentorial), and the presence or absence of hypointense foci were compared across DVAs with and without high-signal-intensity abnormalities. The correlation between patient age and the size of any high-signal-intensity abnormality was analyzed using linear regression. Results: Forty-two of 137 DVAs (30.7 %) had high-signal-intensity abnormalities. An adjusted prevalence of 18/71 (25.4 %) was obtained after excluding patients with considerable underlying white matter disease. Only DVA location (supratentorial) was associated with the presence of high-signal-intensity abnormalities (p < 0.05). There was a significant correlation between patient age and the size of high-signal-intensity abnormalities (p < 0.01). Conclusions: 3D FLAIR imaging permits detection of small high-signal-intensity abnormalities within the drainage territory of DVAs. The size of high-signal-intensity abnormalities increased with patient age. © 2014 Japan Radiological Society.",,"Umino, M.;Maeda, M.;Matsushima, N.;Matsuura, K.;Yamada, T.;Sakuma, H.",2014,July,,0,
690,Impact of albuminuria on early neurological deterioration and lesion volume expansion in lenticulostriate small infarcts,"Background and Purpose - Albuminuria, a marker of chronic kidney disease, is associated with an increased risk of incident stroke and unfavorable long-term outcomes. However, the association of albuminuria with short-term outcomes and change in infarct volume in patients with acute small subcortical infarction remains unknown. Methods - We retrospectively reviewed 85 consecutive patients with acute small subcortical infarcts in the lenticulostriate artery territory who were admitted to our stroke center within 24 hours of symptom onset and underwent serial diffusionweighted imaging (DWI). Albuminuria was determined based on the urinary albumin-to-creatinine ratio obtained from a first morning spot urine after admission. Infarct volume was measured on axial sections of the initial and follow-up DWI. Early neurological deterioration (END) was defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale score during the first 5 days after admission. Results - Albuminuria (UACR ≥30 mg/g creatinine) was observed in 14 of 18 patients with END (77.8%) and in 25 of 67 patients without END (37.3%), P=0.002. Multivariate logistic regression analysis revealed that albuminuria was associated with END after adjustment for age, low estimated glomerular filtration rate (<60 mL/min per 1.73 m2), and infarct volume on initial DWI (odds ratio, 6.64; 95% confidence interval, 1.62-27.21; P=0.009). In addition, albuminuria was an independent predictor of increase in infarct volume using multivariate linear regression analysis (β coefficient=0.217; P=0.038). Conclusions - Our findings suggest that albuminuria is associated with END and infarct volume expansion in patients with small subcortical infarcts in the lenticulostriate artery territory. © 2013 American Heart Association, Inc.",,"Umemura, T.;Senda, J.;Fukami, Y.;Mashita, S.;Kawamura, T.;Sakakibara, T.;Sobue, G.",2014,February,,0,
691,Pathogenesis and neuroimaging of cerebral large and small vessel disease in type 2 diabetes: A possible link between cerebral and retinal microvascular abnormalities,"Diabetes patients have more than double the risk of ischemic stroke compared with non-diabetic individuals, and its neuroimaging characteristics have important clinical implications. To understand the pathophysiology of ischemic stroke in diabetes, it is important to focus not only on the stroke subtype, but also on the size and location of the occlusive vessels. Specifically, ischemic stroke in diabetes patients might be attributed to both large and small vessels, and intracranial internal carotid artery disease and small infarcts of the posterior circulation often occur. An additional feature is that asymptomatic lacunar infarctions are often seen in the basal ganglia and brain stem on brain magnetic resonance imaging. In particular, cerebral small vessel disease (SVD), including lacunar infarctions, white matter lesions and cerebral microbleeds, has been shown to be associated not only with stroke incidence, but also with the development and progression of dementia and diabetic microangiopathy. However, the pathogenesis of cerebral SVD is not fully understood. In addition, data on the association between neuroimaging findings of the cerebral SVD and diabetes are limited. Recently, the clinical importance of the link between cerebral SVD and retinal microvascular abnormalities has been a topic of considerable interest. Several clinical studies have shown that retinal microvascular abnormalities are closely related to cerebral SVD, suggesting that retinal microvascular abnormalities might be pathophysiologically linked to ischemic cerebral SVD. We review the literature relating to the pathophysiology and neuroimaging of cerebrovascular disease in diabetes, and discuss the problems based on the concept of cerebral large and small vessel disease.",basal ganglion;brain hemorrhage;brain ischemia;clinical study;clinical trial;congenital malformation;controlled study;dementia;diabetic microangiopathy;diabetic patient;diabetic retinopathy;disease course;human;internal carotid artery;lacunar stroke;neuroimaging;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;retina;skull;white matter lesion,"Umemura, T.;Kawamura, T.;Hotta, N.",2016,,,0,
692,Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?,"Recent studies have revealed that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia, especially those related to Alzheimer's disease (AD). Basic research suggests that insulin accelerates Alzheimer-related pathology through its effects on the amyloid beta (Abeta). Several pathological studies with autopsy samples have demonstrated, however, that dementia subjects with diabetes have less AD-related neuropathology than subjects without diabetes. We and others have reported that small vessel diseases affect cognitive function in older diabetics. Asymptomatic ischemic lesions in T2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency between the basic research and clinicopathological studies. Longitudinal follow-up of T2DM subjects without overt dementia using both amyloid imaging and magnetic resonance imaging may elucidate these issues. Following up until the development of overt dementia would make it possible to compare both amyloid load and ischemic lesions before and after the development of dementia. Moreover, amyloid imaging in non-demented older people with or without insulin resistance would verify the role of insulin in the processing and deposition of Abeta. Vascular risk factors may represent a therapeutic target, while neurodegenerative pathologies have not yet been amenable to treatment. It remains to be investigated whether medical interventions on vascular risk factors have protective effects against the development and progress of dementia.","Age of Onset;Aging;Alzheimer Disease/ etiology/pathology/physiopathology;Brain Mapping;Cognition Disorders/ etiology/pathology/physiopathology;Diabetes Mellitus/drug therapy/physiopathology/psychology;Diabetes Mellitus, Type 2/ complications/drug therapy/physiopathology;Female;Humans;Male;Risk Factors","Umegaki, H.",2010,Jan,10.1093/ageing/afp211,0,
693,Evaluation of white matter damage in patients with Alzheimer's disease and in patients with mild cognitive impairment by using diffusion tensor imaging,"PURPOSE: The objective of this study was to evaluate white matter tissue damage in patients with Alzheimer's disease (AD) and in patients with mild cognitive impairment (MCI) using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Forty-seven subjects were evaluated: 14 patients with AD, 15 with MCI and 18 healthy volunteers. All subjects were studied using conventional magnetic resonance imaging (MRI) and DTI (32 directions) with a 1.5 T magnet. Fractional anisotropy (FA) was measured in the following regions: frontal, occipital, parietal and temporal white matter and in the genu and splenium of the corpus callosum. The results were compared between the different groups and correlated with the Mini-Mental State Evaluation (MMSE) scores. RESULTS: A statistically significant difference was obtained between controls and MCI patients (p < 0.007) and between controls and AD patients (p < 0.05) with regard to FA of the white matter in the splenium. A statistically significant difference was obtained between controls and AD patients with regard to FA in the genu (p < 0.016). Moreover, there was a statistically significant difference between controls and AD patients considering the genu (p < 0.016) and the frontal white matter on the right side (p < 0.024). The MMSE scores correlated with the FA values measured in the genu, the splenium and frontal white matter on the right side. No significant differences were identified between patients with AD and those with MCI. CONCLUSIONS: DTI could be of value in the early detection of white-matter damage in patients with MCI and AD. The DTI values correlate with the neuropsychological tests.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Anisotropy;Brain/ pathology;Cognition Disorders/ diagnosis/pathology;Corpus Callosum/pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Frontal Lobe/pathology;Humans;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Occipital Lobe/pathology;Parietal Lobe/pathology;Temporal Lobe/pathology","Ukmar, M.;Makuc, E.;Onor, M. L.;Garbin, G.;Trevisiol, M.;Cova, M. A.",2008,Sep,10.1007/s11547-008-0286-1,0,
694,Cerebral blood flow and metabolism in multi-infarct dementia,"Cerebral blood flow and oxygen metabolism were studied in three aged normal volunteers and 10 patients with multi-infarct dementia (MID) by positron emission tomography using O-15. The diagnosis of MID was done according to Loeb's modified ischemic score and X-ray CT findings. The MID patients, whose X-ray CT showed localized low density areas in the subcortical white matter and basal ganglia and thalamus, were studied. No occlusion was observed at the anterior cerebral artery and/or middle cerebral artery on cerebral angiography. All cases of MID were mild dementias. Regional CBF, rOEF and rCMRO2 were measured by the steady state technique described by Terry Jones et al. The values of rCBF in MID patients were significantly low as compared with those of aged normal subjects in frontal, temporal, occipital, parietal cortices and thalamus. The values of CMRO2 in MID were significantly low in frontal, temporal, occipital cortices and thalamus as compared with normal subjects, and 0.52 in MID patients. The MID patients in the early stage of dementia showed an increased oxygen extraction fraction, and this fact suggests that ischemia is a significant pathogenic mechanism in the production and progression of multi-infarct dementia. The degrees of CBF and CMRO2 in MID compared with normal subjects were most remarkable in the frontal cortex. The impairment of mental functions in MID is probably caused by the decreased neuronal activities in the frontal association cortex.",radioisotope;aged;brain blood flow;brain cortex;central nervous system;human;major clinical study;metabolism;multiinfarct dementia;peripheral vascular system;priority journal,"Ujike, T.;Terashi, A.;Soeda, T.",1985,,,0,
695,Endothelial Activation Is Associated With Cognitive Performance in Patients With Hypertension,"BACKGROUND: Hypertension is associated with the occurrence of cognitive deficits and dementia, probably because hypertension is a major risk factor for the occurrence of brain damage as a result of cerebral small vessel disease (cSVD). Endothelial activation and inflammation have been suggested to play an important role in the pathogenesis of cSVD. We investigated if compound scores of endothelial activation or inflammation, based on several blood markers, are associated with cognitive performance 3 years later in patients with essential hypertension. METHODS: At baseline, levels of blood markers of endothelial activation (soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), sP-selectin, and sE-selectin) and markers of inflammation (neopterin, C-reactive protein, and sICAM-1) were measured and transformed into compound scores using z-scores. In addition, a brain magnetic resonance imaging (MRI) was performed to determine the presence of cSVD-related MRI markers. Three years later, patients underwent a neuropsychological assessment to determine cognitive performance. RESULTS: A total of 101 patients with hypertension were included in the present study. In multiple linear regression analyses with correction for demographics and MRI markers, the compound score of endothelial activation (B = -0.19, 95% confidence interval = -0.34 to -0.04, P = 0.014), but not of inflammation (B = -0.09, 95% confidence interval = -0.22 to 0.05, P = 0.198), was associated with worse cognitive performance. CONCLUSIONS: Our results show that an overall measure of endothelial activation is associated with cognitive performance in patients with essential hypertension. This indicates that a process involving endothelial activation might play a role in the pathogenesis of cognitive problems in patients with hypertension.",,"Uiterwijk, R.;Huijts, M.;Staals, J.;Rouhl, R. P.;De Leeuw, P. W.;Kroon, A. A.;Van Oostenbrugge, R. J.",2016,Apr,10.1093/ajh/hpv122,0,
696,Relationship between gray matter volume and cognitive learning in CIS patients on disease-modifying treatment,"Background Repeated administration of Paced Auditory Serial Addition Test (PASAT) results in a considerable learning effect in short- or long-term follow-up studies. However, the relationship between PASAT learning and changes in magnetic resonance imaging (MRI) parameters is yet to be investigated. Objectives The aim of this study is to determine if change in brain MRI metrics predicts evolution of PASAT in high functioning clinically isolated syndrome (CIS) patients on disease-modifying treatment (DMT).Methods This prospective 48-month observational study examined 128 CIS patients treated with 30 μg of intramuscular interferon beta-1a once a week. The correlation between PASAT and MRI measures was assessed at baseline, at 6 months and then annually over the 48-month follow up. Linear mixed model analysis adjusted for age, gender, education and DMT was used to model the temporal association between MRI measures and PASAT performance.Results MRI revealed 2.5% gray matter (GM) volume loss and 4.3 point increase in PASAT score over 48 months. MS patients evidenced significantly greater PASAT score absolute change, had lower loss of GM volume (p =.008) but not significant change in cortical (p =.061), white matter (p =.086) or whole brain volumes (p =.879).Conclusions The present study reveals a significant relationship between higher PASAT learning effect and less GM atrophy in CIS patients on DMT. These findings suggest that change in PASAT associated more with GM than WM pathology, and that treatment strategies oriented toward GM volume preservation may play an important role in prevention of cognitive deterioration in CIS patients. © 2014 Elsevier B.V. All rights reserved.",,"Uher, T.;Benedict, R. H. B.;Horakova, D.;Bergsland, N.;Dusankova, J. B.;Tyblova, M.;Ramasamy, D. P.;Seidl, Z.;Vaneckova, M.;Krasensky, J.;Havrdova, E.;Zivadinov, R.",2014,15,,0,
697,Cerebral blood volume in Alzheimer's disease and correlation with tissue structural integrity,"A vascular component is increasingly recognized as important in Alzheimer's disease (AD). We measured cerebral blood volume (CBV) in patients with probable AD or Mild Cognitive Impairment (MCI) and in elderly non-demented subjects using a recently developed Vascular-Space-Occupancy (VASO) MRI technique. While both gray and white matters were examined, significant CBV deficit regions were primarily located in white matter, specifically in frontal and parietal lobes, in which CBV was reduced by 20% in the AD/MCI group. The regions with CBV deficit also showed reduced tissue structural integrity as indicated by increased apparent diffusion coefficients, whereas in regions without CBV deficits no such correlation was found. Subjects with lower CBV tended to have more white matter lesions in FLAIR MRI images and showed slower psychomotor speed. These data suggest that the vascular contribution in AD is primarily localized to frontal/parietal white matter and is associated with brain tissue integrity.",Aged;Alzheimer Disease/diagnosis/ pathology/ physiopathology;Brain/ blood supply/pathology/physiopathology;Cerebrovascular Circulation/ physiology;Cognition Disorders/diagnosis/pathology/physiopathology;Female;Humans;Male;Middle Aged;Neurons/pathology;Neuropsychological Tests;Synaptic Transmission/physiology,"Uh, J.;Lewis-Amezcua, K.;Martin-Cook, K.;Cheng, Y.;Weiner, M.;Diaz-Arrastia, R.;Devous, M., Sr.;Shen, D.;Lu, H.",2010,Dec,10.1016/j.neurobiolaging.2008.12.010,0,
698,Subcortical dementia associated with striking enlargement of the Virchow-Robin spaces and transneural degeneration of the left mammillo-thalamic tract,"We report a case of subcortical dementia in a 68-year-old woman. MR examination of the patient's brain revealed two types of alterations as a possible cause of the dementia, both anomalous in respect of their entity and incidence: the first was a striking enlargement of the Virchow-Robin spaces, and the second an anterograde transneural degeneration of the left mammillo-thalamic tract and mammillary body secondary to a lacunar infarction of the ipsilateral anterior thalamus. Copyright © 2001 S. Karger AG, Basel.",aged;article;case report;dementia;disease association;female;human;infarction;mammillary body;nerve cell degeneration;nuclear magnetic resonance imaging;priority journal;thalamus;thalamus anterior nucleus,"Uggetti, C.;Egitto, M. G.;Pichiecchio, A.;Sinforiani, E.;Bevilacqua, M. S.;Cavallini, A.;Micieli, G.",2001,,,0,
699,Prevalence and topography of small hypointense foci suggesting microbleeds on 3T susceptibility-weighted imaging in various types of dementia,"BACKGROUND AND PURPOSE: The prevalence and topography of small hypointense foci suggesting microbleeds on 3T SWI in various types of dementia have not been systematically investigated. The purpose of this study was to determine the prevalence and topography of SHF on 3T SWI in patients with different dementia subtypes. MATERIALS AND METHODS: We included 347 consecutive patients (217 women, 130 men; age range, 42-93 years; mean age, 74 years) who attended our memory clinic and underwent 3T SWI. They were divided into 6 groups: subjective complaints, MCI, AD, DLB, VaD, and FTLD. Two neuroradiologists evaluated the number and location of SHF on SWIs. Statistical analyses were performed to evaluate inter- and intragroup differences. RESULTS: Of the 347 patients, 160 (46.1%) exhibited at least 1 small hypointense focus. This was true in 86% with VaD, 54% with DLB, 48% with AD, 41% with MCI, 27% with FTLD, and 22% with subjective complaints. With the subjective complaints group as a reference, the odds ratio adjusted by age, sex, and arterial hypertension was 9.2 (95% CI, 2.0-43.6) for VaD; 5.4 (95% CI, 1.2-24.3) for AD; 3.1 for DLB (95% CI, 1.1-8.8); 2.0 for MCI (95% CI, 0.5-8.1); and 1.5 for FTLD (95% CI, 0.4-5.4). There was a significant lobar predilection for AD, DLB, and FTLD groups (P < .05). CONCLUSIONS: On 3T SWI, patients with VaD, AD, and DLB manifested a high SHF prevalence. In patients with AD, DLB, and FTLD, the SHF exhibited a lobar predilection.","Adult;Aged;Aged, 80 and over;Brain/ pathology;Cerebral Hemorrhage/ epidemiology/ pathology;Comorbidity;Dementia/ epidemiology/ pathology;Female;Humans;Japan/epidemiology;Magnetic Resonance Imaging/ statistics & numerical data;Male;Middle Aged;Prevalence;Reproducibility of Results;Risk Assessment;Sensitivity and Specificity","Uetani, H.;Hirai, T.;Hashimoto, M.;Ikeda, M.;Kitajima, M.;Sakamoto, F.;Utsunomiya, D.;Oda, S.;Sugiyama, S.;Matsubara, J.;Yamashita, Y.",2013,May,10.3174/ajnr.A3332,0,
700,Association of neurological diseases with metabolic syndrome among out-patients,"Background and Objective: Metabolic syndrome (MetS) is highly prevalent in Japan; however, most previous surveys have studied only adults able to engage fully in normal daily activities, after excluding persons with diseases or disabilities. Recently, lifestyle-related risk factors have been strongly linked to a number of major diseases. In particular, the incidence of atherosclerotic vascular diseases associated with MetS has increased markedly, and this trend is projected to continue. We focused on the prevalence of MetS among out-patients with neurological diseases. Patients and methods: The subjects for this hospital-based study were 713 out-patients with various neurological diseases (329 men, mean age 65.2 ± 14.5 yr, age range 40-78 yr, and 384 women, mean age 64.6 ± 15.3 yr, age range 40-88 yr) who presented at the Department of Neurology, Nara Medical University Hospital. A total of 120 patients had cerebral infarction, 102 Parkinson's disease, 32 spinal spondylosis, 30 headache, 32 myositis, and the rest various other neurological diseases. MetS was diagnosed according to the criteria proposed by The Japanese Society of Internal Medicine in 2005. The cutoff values for waist circumference (WC) were greater than 85 cm in men and 90 cm in women. A diagnosis of MetS additionally required two or more of the following: a serum triglyceride level (TG) of at least 150 mg/dl and/or a high-density lipoprotein cholesterol level (HDL-C) of less than 40 mg/dl; a blood pressure (BP) of greater than 130/85; or a fasting plasma glucose level (FPG) of greater than 110 mg/dl. Visceral fat accumulation was measured by abdominal CT scanning (N2system, K.K., Japan). Results: WC positively correlated with visceral fat area as determined by CT scanning. WC also positively correlated with TG in both sexes and FBS in women, but negatively correlated with HDL-C in both sexes. The mean prevalence of MetS among subjects 40 to 70 years of age was 25.1% in men and 12.6% in women. To assess the incidence of MetS in the absence of cerebrovascular disease (CVD), we performed a subgroup analysis of patients with and without CVD. The risk of MetS was similar in outpatients without CVD and those with CVD. The prevalence of Pre MetS (defined as WC plus one risk factor) plus MetS was 50% in men and 20% in women. The prevalence of MetS in outpatients with neurological diseases was similar to that in the general population. Conclusion: The risk of atherosclerotic diseases in out-patients with neurological diseases is similar to that in the general population, potentially increasing the risk of unfavorable outcomes. The recognition and management of MetS represents an important challenge for physicians and other healthcare professionals. Strategies aimed at reducing risk factors for MetS are urgently required.",high density lipoprotein;triacylglycerol;adult;aged;article;atherosclerosis;cerebrovascular disease;clinical feature;controlled study;daily life activity;dementia;disease association;female;glucose blood level;headache;human;incidence;intraabdominal fat;Japan;major clinical study;male;metabolic syndrome X;myositis;neurologic disease;outpatient care;Parkinson disease;prevalence;sex difference,"Ueno, S.;Furiya, Y.;Sugie, K.;Kawahara, M.;Kataoka, H.;Saito, K.;Kiriyama, T.;Kinoshita, S.;Hirano, M.",2007,,,0,
701,Three cases of cerebral infarction with prolonged increase of protein content of cerebrospinal fluid,"Examination of cerebrospinal fluid (CSF) is important as a diagnostic procedure of cerebrovascular disease, although CT scan is coming into general use. Generally, CSF protein content increases markedly in many cases of cerebral hemorrhage and moderately in about half cases of cerebral infarction. Usually, protein content in CSF returns to normal within a few months after the attack of cerebral hemorrhage or infarction. Very rarely, protein content of CSF remains highly increased for longer period in cerebral infarctions, but its cause is unknown. We have observed three cases of cerebral infarctions which maintained high content of CSF protein for 3 to 8 years, and studied their clinical features and CT scans in search for causes of persistent high content of CSF protein. Case 1 was a 70-yr-old man with longstanding hypertension, who became hemiplegic on the left side in the spring of 1973, when his systolic blood pressure was 230 mmHg. He was improving clinically, but in July 1974, he had an attack of Jacksonian seizure and lost consciousness. Slight dementia was noticed on recovery after several weeks. He had two more attacks of apoplexy within two and a half years. Case 2 was a 71-yr-old man who had uncontrolled high blood pressure for several years, and who was confused and developed right hemiplegia in November 1975. Despite rapid recovery, he lost consciousness again in July 1977, with left hemiplegia, which was followed by another attack of left hemiplegia after one month. Case 3 was a 61-yr-old man who had hypertension and diabetes mellitus for several years, who developed left hemiplegia in November 1970, when his blood pressure was 220/110 mmHg. In April 1972, he noticed dysarthria and right hemiparesis, which became worse by another stroke after three years. The contents of CSF protein in each case were as follows; Case 1: 63-106 mg/dl, Case 2: 59-210 mg/dl, Case 3: 67-210 mg/dl. All these cases had more than 3 times cerebrovascular accidents. They had pseudobulbar palsy and tetraplegia, and in general findings they had obesity, hypertension, arteriosclerosis and hyperlipidemia. Two cases had dementia and urinary incontinence, and one case had diabetes mellitus. Other diseases which might raise the CSF protein were denied in each case. CT scan showed large and/or multiple low density areas which involved the cerebral cortex. The recurrence of cerebrovascular accidents and widespread lesions may relate to the persistent high content of CSF protein in cerebral infarctions.",brain infarction;central nervous system;focal epilepsy;major clinical study;protein cerebrospinal fluid level,"Ueno, E.;Hanyu, T.;Oguchi, K.",1980,,,0,
702,A case of non-convulsive status epilepticus worsened Wernicke's aphasia reversely,"A 62-year-old right-handed woman had presented progressive speech impediment over 4 months. She was alert without any convulsions or involuntary movements. Neurological examination showed Wernicke's aphasia, constructional apraxia. Her magnetic resonance imaging (MRI) showed an old cerebral infarction in the left parieto-occipital area, in addition to ischemic changes in the bilateral deep white matter. Electroencephalography (EEG) revealed periodic lateralized epileptiform discharges (PLEDs) predominant in the posterior left hemisphere. The PLEDs as well as the cortical symptoms improved after an administration of anti-convulsive agents, thus establishing the diagnosis of non-convulsive status epilepticus (NSE). It should be emphasized that NSE manifesting as Wernicke's aphasia should be distinguished from dementia syndrome because it is a treatable disorder.",,"Ueki, Y.;Terada, K.;Otsuka, A.;Kanda, M.;Akiguchi, I.",2000,2000,,0,
703,[Epidemiological study of the prognosis and relevant factors of demented patients],"One hundred twenty patients diagnosed as having dementia at the Center for Elderly Dementia in Hyogo College of Medicine, were recruited for this study to investigate the factors related to the prognosis of dementia. Patients were classified into the following two groups: those staying at home (group 1); those who died at home (group 2). The proportion of various dementias was almost equal in each group: vascular dementia, 30%; senile dementia of Alzheimer's type, 40%; mixed dementia, 20%; Alzheimer's disease, 10%. The average duration of disease in the two groups were not significantly different. The average age of onset in group 2 was higher than that in group 1. The rate of those with severe dementia was higher in group 2 than group 1. Those in group 2 scored less on the Mini-Mental State examination than those in group 1. Symptoms of dementia were assessed by the modified GBS-scale. In group 2, patients scored higher in impaired intellectual and motor functions. The CT findings suggested cortical atrophy, ventricular enlargement and periventricular lucency more often in group 2 than in group 1. Laboratory findings revealed that decrease in red blood cell count, hemoglobin, hematocrit and serum protein were more apparent in group 2 than group 1. It was considered that impaired motor functions, cortical atrophy, white matter lesions, anemia and malnutrition enhanced the probability of death. The study has confirmed that the prognosis of dementia is not only related to intellectual impairment but also deteriorated physical conditions such as motor dysfunction, anemia and malnutrition.",Aged;Alzheimer Disease/mortality/physiopathology;Dementia/*mortality/physiopathology;Female;Humans;Male;Prognosis,"Ueki, A.;Miyoshi, K.;Fujita, H.;Shinjo, H.;Nakajima, T.;Iwasaki, S.;Miwa, C.;Kitamura, E.;Oohara, K.;Takeda, T.;et al.",1995,Oct,,0,
704,Neuropsychological Features of Microbleeds and Cortical Microinfarct Detected by High Resolution Magnetic Resonance Imaging,"BACKGROUND: Lobar microbleeds (MBs) and cortical microinfarct (CMI) are caused by cerebral amyloid angiopathy in the elderly and increase in number in Alzheimer's disease. OBJECTIVE: The aim of this study is to elucidate the effects of lobar MBs and CMIs on cognitive function. METHODS: The subjects were outpatients who visited the memory clinic of Mie University Hospital. Among 120 subjects, 109 patients fulfilled the inclusion criteria. We quantitatively estimated MBs and CMIs using double inversion recovery and 3D FLAIR images of 3T MRI. Neuropsychological assessments included intellectual, memory, constructional, and frontal lobe function. RESULTS: Of the 109 patients, MBs and CMIs were observed in 68 (62%) and 17 (16%) subjects, respectively. Of the 68 patients with MBs, lobar MBs were found in 28, deep MBs in 8 and mixed MBs in 31. In each age group, the number of MBs increased in patients with CMI (CMI+ group) than those without CMI (CMI- group), and MBs and CMIs additively decreased MMSE scores. In psychological screens, the MBs+ group with more than 10 MBs showed significantly lower scores of category- and letter-WF than MB- group. The CMI+ group showed significantly worse scores than CMI- group in Japanese Raven's coloured progressive matrices, Trail Making Test-A, category- and letter-word fluency and copy and drawing of figures. CONCLUSION: Lobar MBs and CMIs in the elderly frequently coexisted with each other and additively contributed to cognitive impairment, which is mainly predisposed to frontal lobe function.",Bleeding;cerebral amyloid angiopathy;dementia;infarct;magnetic resonance imaging;neuropsychological test,"Ueda, Y.;Satoh, M.;Tabei, K.;Kida, H.;Ii, Y.;Asahi, M.;Maeda, M.;Sakuma, H.;Tomimoto, H.",2016,May 7,10.3233/jad-151008,0,
705,Prevalence and etiology of dementia in a Japanese community,"BACKGROUND AND PURPOSE: We sought to determine the type-specific prevalence of dementia and its risk factors in elderly persons from the Japanese community of Hisayama. METHODS: We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women) aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have dementia by computed tomography or autopsy during the subsequent 54-month period. Factors relevant to dementia were compared between 27 patients with vascular dementia and 789 control subjects without dementia in a retrospective fashion. RESULTS: The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at 6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high hematocrit were significantly (p less than 0.05) and independently associated with the occurrence of vascular dementia. CONCLUSIONS: Prevalence of dementia among the Hisayama residents was relatively identical to that previously reported, but vascular dementia was more predominant. Risk factors for vascular dementia were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia among the Japanese population.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/epidemiology;Brain/pathology/radiography;Cerebral Infarction/classification/complications;Dementia/classification/*epidemiology/etiology;Dementia, Vascular/etiology;Female;Humans;Japan/epidemiology;Male;Odds Ratio;Prevalence;Regression Analysis;Sex Factors;Survival Analysis","Ueda, K.;Kawano, H.;Hasuo, Y.;Fujishima, M.",1992,Jun,,0,
706,Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014,"This study elucidates the genotypic and phenotypic spectrum and histopathological findings related to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Japan. For this single-center retrospective observational study, we enrolled 215 patients who were clinically suspected of having CADASIL and were examined at Kumamoto University from 1997 to 2014, and we diagnosed CADASIL in 70 patients. We found 19 different NOTCH3 mutations in the patients, with the NOTCH3 Arg133Cys mutation being found most frequently. We also found the Arg75Pro mutation, a cysteine-sparing NOTCH3 mutation. CADASIL patients with this Arg75Pro mutation were frequently found throughout Japan, and fewer patients with the Arg75Pro mutation showed MRI hyperintensity in the anterior temporal pole compared with patients with other NOTCH3 mutations. Significantly more CADASIL patients with the NOTCH3 Arg133Cys mutation had hyperintensity in the external capsule compared with CADASIL patients with the other mutations not including the NOTCH3 Arg75Pro mutation. We also showed postmortem pathological findings of the first Japanese CADASIL case with the NOTCH3 Arg133Cys mutation, and histopathological findings of fresh frozen skin biopsy specimens of CADASIL patients. In conclusions, the spectrum of NOTCH3 mutations in Japanese CADASIL patients may be partially explained by founder effects. Genotype–phenotype correlations may exist in CADASIL, which should be considered so as to make an accurate diagnosis of CADASIL in each population. Fresh frozen skin biopsy specimens may aid detection of Notch3 deposits on vascular walls for an improved diagnosis of CADASIL.",amino acid;arginine;cysteine;DNA;Notch3 receptor;adult;article;CADASIL;DNA sequence;female;gene mutation;genetic screening;genotype;genotype phenotype correlation;histopathology;human;human tissue;Japan;major clinical study;male;nuclear magnetic resonance imaging;observational study;patient referral;phenotype;polymerase chain reaction;priority journal;retrospective study;skin biopsy;university,"Ueda, A.;Ueda, M.;Nagatoshi, A.;Hirano, T.;Ito, T.;Arai, N.;Uyama, E.;Mori, K.;Nakamura, M.;Shinriki, S.;Ikeda, K.;Ando, Y.",2015,,,0,
707,CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant vascular encephalopathy that has been mainly reported in Europe and the United States. Recently, this disease has been reported in Japan and the increasing number of reported cases has been attracting attention. Currently, the clinical diagnosis of CADASIL is based on the satisfaction of the following conditions: (1) development of the condition at a relatively young age (40-50 years), (2) no risk for stroke, (3) repeated attacks of lacunar infarction with gradual progression to pseudobulbar paralysis and dementia (migraine, emotional disturbance, cerebral infarction, and dementia in 30%, 20%, 85%, and 30-90% of patients, respectively), and (4) family members with similar symptoms (autosomal dominant inheritance). The diagnosis is also established on the basis of the following findings of imaging and laboratory studies: the presence of (1) leukoaraiosis and multiple small infarcts in the bilateral deep white matter, basal ganglia, thalamus, and pons revealed by MRI; (2) granular osmiophilic material (COM) around the vascular smooth muscles in the brain, skeletal muscle, peripheral nerves, and skin demonstrated by electron microscopy; and (3) Notch3 mutations revealed by DNA analysis. Characteristics of CADASIL patients in Japan: Between 1997 and 2008, 38 CADASIL families have been reported in Japan. The age at onset of local neurological symptoms ranged from 15 to 71 years (mean 42. 3 ± 11.4 years). All patients except one with borderline hypertension were normotensive or hypotensive. Out of 45 patients, 18 (40%) had migraine; 37 (82.2%) had repeated cerebral ischemic attacks including transient ischemic attacks (TIA); and 22 (48.9%), including borderline cases, had intellectual impairment. Nine of 38 patients (23.7%) had pseudobulbar paralysis. The retinal arteries were narrowed in 4 of 16 patients. The patients were distributed nationwide. Mutations in exon 4 have been reported in 22 of 31 families (71%). It is expected that an increase in the number of reported cases will lead to the discovery of other mutations associated with this condition. The mechanism of development of CADASIL due to Notch3 mutations is still unknown. However, a recent study has revealed that the Notch3 ectodomain is a major component of GOM. On binding to its ligand, Notch3 normally undergoes proteolytic cleavage, resulting in the clearance of the extracellular domain. However, in CADASIL, it accumulates as GOM and potentially inhibit the normal metabolism of smooth muscle cells.",adolescent;adult;aged;article;autosomal dominant disorder;brain infarction;brain ischemia;CADASIL;clinical article;female;gene mutation;human;intellectual impairment;Japan;leukoaraiosis;male;migraine;nuclear magnetic resonance imaging;pseudobulbar palsy;transient ischemic attack,"Uchino, M.",2008,,,0,
708,Blood pressure reduction and risk of dementia in patients with stroke: rationale of the dementia assessment in PROGRESS (Perindopril Protection Against Recurrent Stroke Study). PROGRESS Management Committee,"High blood pressure is a known risk factor for multi-infarct dementia, a subtype of dementia caused by the occurrence of several strokes. However, this form of dementia is relatively uncommon and the influence of blood pressure on the risk of other subtypes of vascular dementia remains to be clarified. Furthermore, recent studies have suggested that vascular risk factors could also play a part in Alzheimer's disease. One of the aims of Perindopril Protection Against Recurrent Stroke Study (PROGRESS) is to test the hypothesis that blood pressure decreasing treatment based on perindopril would reduce the incidence of dementia among patients with cerebrovascular disease. The dementia procedures in PROGRESS involve a classical two-phase design, with an initial screening phase based mainly on the Mini-Mental State Examination - a simple, brief, and widely used screening test for dementia. The second phase involves a diagnostic assessment for dementia in individuals screened as positive according to the criteria of the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (4th ed.). In this project, two other domains of the relationship between vascular risk factors and cognition are being explored in relation to PROGRESS substudies. The apolipoprotein E polymorphism, a genetic risk factor for Alzheimer's disease, is being determined in each patient, as part of the genetic substudy. This will allow study of the relationship between this polymorphism and blood pressure, and of the effect of blood pressure decreasing treatment on the risk of dementia. The magnetic resistance imaging substudy will improve understanding of the relationship between blood pressure decreasing and the occurrence of cerebral white matter lesions, which are known to be related to cognitive decline and dementia.",Angiotensin-Converting Enzyme Inhibitors [therapeutic use];Blood Pressure [drug effects];Dementia [diagnosis] [etiology] [prevention & control];Perindopril [therapeutic use];Risk Factors;Stroke [complications] [drug therapy] [physiopathology];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-htn,"Tzourio, C.;Anderson, C.",2000,,,0,
709,"Hypertension, cognitive decline, and dementia: An epidemiological perspective","Hypertension is a known risk factor for stroke, and thus for vascular dementia. However, recent large observational studies have suggested that high blood pressure may also play a role in Alzheimer's disease. The mechanisms linking hypertension to Alzheimer's disease remain to be elucidated, but white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association. It is not yet clearly established whether lowering blood pressure reduces the risk of white matter lesions and dementia, so large trials dealing with this question are eagerly awaited. These future trials could confirm the hope that, by lowering blood pressure, we may have a preventive treatment for dementia. This issue is of major importance, as the number of cases of dementia is expected to rise sharply in the near future. © 2007, LLS SAS.",,"Tzourio, C.",2007,2007,,0,
710,Rapid spongiform degeneration of the cerebrum and cerebellum in Creutzfeldt-Jakob encephalitis: Serial MR findings,We report the cerebral MR imaging findings in a patient with pathologically proved Creutzfeldt-Jakob disease in whom predominant gray and white matter degeneration was seen within 1 year of symptom onset. The initial MR signal abnormalities in the basal ganglia were subtle. A follow- up MR examination revealed diffuse cerebral and cerebellar atrophy and demyelination.,,"Tzeng, B. C.;Chen, C. Y.;Lee, C. C.;Chen, F. H.;Chou, T. Y.;Zimmerman, R. A.",1997,March,,0,
711,White matter changes in GM1 gangliosidosis,Background: GM1 gangliosidosis is a disorder due to GLB1 gene mutation.Case characteristics: A 4-yr-old boy with neuroregression and optic atrophy with periventricular hyperintensity on magnetic resonance imaging.Outcome: Beta galactosidase enzyme activity was low which was confirmed by GLB1 sequencing.Message: We highlight the white matter changes in late infantile GM1 gangliosidosis.,,"Tuteja, M.;Bidchol, A. M.;Girisha, K. M.;Phadke, S. R.",2015,2015,,0,
712,Heritability of leukoaraiosis in hypertensive sibships,"Ischemic damage to the subcortical white matter of the brain, referred to as leukoaraiosis, is a frequent complication of hypertension-related microvascular disease and contributes to the risk of stroke and vascular dementia. A large genetic contribution to this late-life form of target organ damage was suggested by a study of elderly male twins. As part of the Genetic Epidemiology Network of Arteriopathy (GENOA), 483 non-Hispanic white subjects were recruited to undergo MRI for determination of the brain volume of leukoaraiosis (291 women and 192 men from 210 sibships providing 434 sibling pairs; mean age+/-SD=65.2+/-7.3 years). The GENOA-Rochester sibships contain 2 or more siblings with essential hypertension diagnosed before age 60. The frequency distribution of the volume of leukoaraiosis was positively skewed, with a median value of 6.61 cm3 (interquartile range: 4.77 to 9 0.83 cm3). Variance component models were used to estimate the heritability (ie, the proportion of phenotypic variation caused by additive genetic factors). After logarithm transformation of the volume of leukoaraiosis, the estimated heritability (+/-SE) was 0.802+/-0.102 (P<0.0001). Adjustments for sex, age, systolic blood pressure, and brain volume reduced the heritability estimate to 0.671+/-0.110 (P<0.0001). This evidence of strong genetic influence on the susceptibility to leukoaraiosis justifies efforts to localize the responsible genes and characterize the predisposing genetic polymorphisms.",Aged;Brain Ischemia/etiology/*genetics/pathology;Female;Humans;Hypertension/*complications;Magnetic Resonance Imaging;Male;Siblings,"Turner, S. T.;Jack, C. R.;Fornage, M.;Mosley, T. H.;Boerwinkle, E.;de Andrade, M.",2004,Feb,10.1161/01.hyp.0000112303.26158.92,0,
713,"Genomic susceptibility Loci for brain atrophy, ventricular volume, and leukoaraiosis in hypertensive sibships","OBJECTIVE: To localize susceptibility genes for alterations in brain structure associated with risk of stroke and dementia. We conducted genomewide linkage analyses for magnetic resonance imaging (MRI) measures of brain atrophy, ventricular, and subcortical white matter hyperintensity (leukoaraiosis) in 689 non-Hispanic white (673 sibling pairs; median age, 61 years) and 544 non-Hispanic black participants (503 sibling pairs; median age, 64 years) from sibships with at least 2 members with essential hypertension. DESIGN, SETTING, AND PATIENTS: We determined brain, ventricular, and leukoaraiosis volumes from axial fluid-attenuated inversion recovery MRI; we calculated brain atrophy as the difference between total intracranial and brain volumes. Microsatellite markers (n = 451) distributed across the 22 autosomes were genotyped, and we used variance components methods to estimate heritability and assess evidence of genetic linkage for each MRI measure. MAIN OUTCOME MEASURES: Brain atrophy ventricular volume, and leukoaraiosis determined from fluid-attenuated inversion recovery MRI. RESULTS: In both races, the heritability of each MRI measure was statistically greater than 0 (P < .001), ranging in magnitude from 0.42 (for ventricular volume in blacks) to 0.69 (for brain atrophy in blacks). Based on multipoint logarithm of odds scores (MLS), the strongest evidence of genetic linkage was observed for brain atrophy on chromosomes 1 (MLS, 3.49 at 161 cM; P < .001) and 17 (MLS, 3.08 at 18 cM; P < .001) in whites; for ventricular volume on chromosome 12 (MLS, 3.67 at 49 cM; P < .001) in blacks and chromosome 10 (MLS, 2.47 at 110 cM; P < .001) in whites; and for leukoaraiosis on chromosome 11 (MLS, 2.21 at 118 cM; P < .001) in whites and chromosome 22 (MLS, 2.02 at 36 cM; P = .001) in blacks. CONCLUSIONS: The MRI measures of structural brain injury are heritable in non-Hispanic black and white sibships ascertained through hypertensive sibling pairs. The susceptibility loci for brain atrophy, ventricular volume, and leukoaraiosis identified by linkage analyses differ among MRI measures and between races.","Atrophy;Brain/ pathology;Cerebral Ventricles/ pathology;Chromosome Mapping;Chromosomes, Human, Pair 13;Disease Susceptibility;European Continental Ancestry Group/genetics;Female;Genetic Linkage/genetics;Genome, Human;Humans;Hypertension/complications/ genetics/pathology;Leukoaraiosis/etiology/ genetics/pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Siblings","Turner, S. T.;Fornage, M.;Jack, C. R., Jr.;Mosley, T. H.;Knopman, D. S.;Kardia, S. L.;Boerwinkle, E.;de Andrade, M.",2009,Jul,10.1001/archneurol.2009.110,0,
714,Genetics of leukoaraiosis,"Computed tomography and magnetic resonance imaging of the brains of elderly individuals frequently show areas of altered signal intensity in the periventricular and subcortical white matter, referred to as leukoaraiosis. Although mildly affected individuals appear asymptomatic, larger burdens of leukoaraiosis are associated with deficits of cognition and gait. Histopathologically, areas of leukoaraiosis invariably show sclerosis, luminal narrowing, and tortuosity of small arteries and arterioles, accompanied by variable degrees of gliosis, demyelination, and axonal loss resulting from ischemia. Genetic variation plays a substantial role in interindividual differences in the volume of leukoaraiosis and its associated adverse clinical outcomes. Characterizing genetic factors contributing to interindividual differences in leukoaraiosis has the potential to enhance understanding of molecular determinants of ischemic brain injury and lead to new approaches to the diagnosis, evaluation, treatment, and prevention of this common form of vascular dementia.",,"Turner, S. T.;Fornage, M.",2002,Sep-Oct,10.1053/jscd.2002.129597,0,
715,Coexistence of Capgras and Frégoli syndromes associated to frontotemporal volume reduction and cerebral white matter hyperintensities,"Background: Delusional misidentification syndromes are conditions in which the patients pathologically misidentify people, places, objects or events. They have been categorized in four subtypes: Capgras, Frégoli, intermetamorphosis and subjective double syndromes. Such syndromes may be present in patients with psychiatric disorders such as schizophrenia and mood disorders, and with neurological diseases such as Alzheimer, Parkinson and brain injury (trauma, vascular). Objectives: To describe and discuss a case of coexistent between Capgras and Frégoli syndromes in a female patient with paranoid schizophrenia and brain MRI findings. Methods: Psychiatric interview and brain MRI scanning. Results: The patient presented structural magnetic resonance imaging periventricular and subcortical white matter hyperintensities on flair images mainly concentrated in the right frontotemporal region and bilateral frontotemporal volume loss. Discussion: The described neuroimaging findings may represent an organic substrate to the delusional misidentification syndromes of the present case. The delusional symptoms in Capgras and Frégoli syndromes could be the result of a right temporolimbic-frontal disconnection which results in impossibility to associate previous memories to new information and consequently misidentifying symptoms. Moreover a volume loss of such cerebral regions, as observed in the present case, may also play a significant role in the development of delusional misidentification syndromes.",,"Turkiewicz, G.;Zanetti, M. V.;Zung, S.;Cordeiro, Q.",2009,2009,,0,
716,SSA 03-4 THE BRAIN SCREENING IN PATIENTS WITH HYPERTENSION,"Observational studies have conveyed the connection between hypertension and cognitive impairment. Several forms of dementia are more frequent in hypertensive subjects or those with previous history of hypertension compared to subjects with normal blood pressure.In many studies, hypertension occuring in mid-life is a risk factor of dementia occuring in later age. Long-standing hypertension will induce structural damages in the brain. It is also widely known that hypertension attributes to small vessel diseases causing lacunar infarcts and white matter lesions associated with cognitive decline. Due to availability and for cost efficiencies, widespread use of MRI in the evaluation of elderly with hypertension is limited. Nevertheless, silent brain infarctions should be sought in all hypertensives patients with neurological deficits and memory loss in particular. As cognitive disturbances are hypertension-related in some parts, suitable cognitive evaluation tests should be warranted in the clinical assessment of all hypertensive patients with cognitive complaints and in all elderly with hypertension. Hypertension is related with impairments in several cognitive domains like attention, language, short & long term memory, visuo-spatial and executive functions.",,"Turana, Y.",2016,Sep,10.1097/01.hjh.0000499884.77354.0e,0,
717,Positron emission tomography examination of cerebral blood flow and glucose metabolism in young CADASIL patients,"BACKGROUND AND PURPOSE: CADASIL causes repeated ischemic strokes leading to subcortical vascular dementia. The purpose of this study was to assess whether cerebral blood flow (CBF) and regional cerebral metabolic rates of glucose (rCMR(gluc)) in CADASIL patients are affected in early adulthood. METHODS: CBF and rCMR(gluc) were examined with positron emission tomography in correlation with magnetic resonance imaging (MRI) in 14 adult (19 to 41 years) CADASIL patients with the Notch3 R133C mutation. Seven patients had experienced transient ischemic attack and 3 had experienced > or =1 strokes. RESULTS: The mean CBF in the CADASIL patients was significantly lower in both frontal (P=0.019) and occipital (P=0.009) white matter (WM) than those in the controls. CBF decreased significantly with increased severity of the disease. The patients had lower mean rCMR(gluc) values than the controls, although differences were not statistically significant. Sum scores of semiquantitative MRI rating scale (Scheltens) correlated significantly with WM CBF but not with rCMR(gluc). CONCLUSIONS: In CADASIL, there is an early and significant decrease in the CBF of WM associated with simultaneous MRI changes. These are obviously caused by the arteriopathy in long penetrating arteries and indicate early tissue damage, also expressed as impaired rCMR(gluc) in the WM.","Adult;Age Factors;Brain/ metabolism/ radionuclide imaging;Cerebrovascular Circulation;Dementia, Multi-Infarct/genetics/ metabolism/ radionuclide imaging;Dementia, Vascular/genetics/metabolism/radionuclide imaging;Glucose/ metabolism;Humans;Magnetic Resonance Imaging;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface;Receptors, Notch;Tomography, Emission-Computed","Tuominen, S.;Miao, Q.;Kurki, T.;Tuisku, S.;Poyhonen, M.;Kalimo, H.;Viitanen, M.;Sipila, H. T.;Bergman, J.;Rinne, J. O.",2004,May,10.1161/01.STR.0000124124.69842.2d,0,
718,Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation,"Background and Purpose - CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. Methods - The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. Results - The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. Conclusions - Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.",,"Tuominen, S.;Juvonen, V.;Amberla, K.;Jolma, T.;Rinne, J. O.;Tuisku, S.;Kurki, T.;Marttila, R.;Pöyhönen, M.;Savontaus, M. L.;Viitanen, M.;Kalimo, H.",2001,2001,,0,
719,Development and validation of a priori risk model for extensive white matter lesions in people age 65 years or older: the Dijon MRI study,"OBJECTIVES: The objective was to develop and validate a risk model for the likelihood of extensive white matter lesions (extWML) to inform clinicians on whether to proceed with or forgo diagnostic MRI. DESIGN: Population-based cohort study and multivariable prediction model. SETTING: Two representative samples from France. PARTICIPANTS: Persons aged 60-80 years without dementia or stroke. Derivation sample n=1714; validation sample n=789. PRIMARY AND SECONDARY OUTCOME MEASURES: Volume of extWML (log cm(3)) was obtained from T2-weighted images in a 1.5 T scanner. 20 candidate risk factors for extWML were evaluated with the C-statistic. Secondary outcomes in validation included incident stroke over 12 years follow-up. RESULTS: The multivariable prediction model included six clinical risk factors (C-statistic=0.61). A cut-off of 7 points on the multivariable prediction model yielded the optimum balance in sensitivity 63.7% and specificity 54.0% and the negative predictive value was high (81.8%), but the positive predictive value was low (31.5%). In further validation, incident stroke risk was associated with continuous scores on the multivariable prediction model (HR 1.02; 95% CI 1.01 to 1.04, P=0.02) and dichotomised scores from the multivariable prediction model (HR 1.28; 95% CI 1.02 to 1.60, P=0.03). CONCLUSIONS: A simple clinical risk equation for WML constituted by six variables can inform decisions whether to proceed with or forgo brain MRI. The high-negative predictive value demonstrates potential to reduce unnecessary MRI in the population aged 60-80 years.",leukoaraiosis;magnetic resonance imaging;predictive risk;receiver operating characteristics;white matter hyperintensities,"Tully, P. J.;Qchiqach, S.;Pereira, E.;Debette, S.;Mazoyer, B.;Tzourio, C.",2017,Dec 29,,0,
720,"The association between systolic blood pressure variability with depression, cognitive decline and white matter hyperintensities: the 3C Dijon MRI study","BACKGROUND: Accumulating evidence links blood pressure variability (BPV) with white matter hyperintensities (WMH) and stroke. The longitudinal association between BPV with late onset depression (LOD) and cognitive decline remains unexplored. METHODS: Prospective cohort study of 2812 participant's age 65 years (median age 72 years, 63.6% female) without dementia or stroke. Serial clinic visits assessed blood pressure, cognitive function, depression disorder, and depressive symptoms. A brain magnetic resonance imaging (MRI) substudy was performed in 1275 persons to examine possible associations with WMH. RESULTS: The interaction between symptomatic LOD and systolic BPV was associated with cognitive decline on the Isaac Set Test [slope -4.45; 95% confidence interval (CI) -8.92 to -0.16, p = 0.04], Benton Visual Retention Test (slope -0.89; 95% CI -1.77 to -0.01, p = 0.049), Mini Mental State Examination (slope -1.08; 95% CI -1.86 to -0.30, p = 0.007) and Finger Tapping Test (slope -7.53; 95% CI -13.71 to -1.34, p = 0.017) but not Trail Making Test-A or -B/A. The MRI substudy demonstrated that systolic BPV was associated with cognitive decline via interactions with depression and total WMH volume, but this was not dependent on either deep or periventricular WMH volumes. CONCLUSIONS: The findings show that the interaction between systolic BPV with symptomatic depression and WMH increases cognitive decline in persons 65 years of age. Future work could extend these findings by examining systolic BPV in relation to cognitive decline and WMH in older populations with depression.",Blood pressure;blood pressure variability;depression;geriatric psychiatry;mild cognitive impairment;white matter hyperintensity,"Tully, P. J.;Debette, S.;Tzourio, C.",2017,Sep 27,,0,
721,White Matter Lesions are Associated with Specific Depressive Symptom Trajectories among Incident Depression and Dementia Populations: Three-City Dijon MRI Study,"OBJECTIVE: Evidence is mixed as to whether periventricular or deep white matter hyperintensities (WMHs) increase the risk for depressive symptoms, partly because of heterogeneity in depression measurement, short follow-up, and confounding by prodromal dementia. The study objective was to evaluate WMH volume in relation to discrete depressive symptoms over 10 years, stratifying by incident depression and dementia. METHODS: In this prospective longitudinal cohort study of a representative population sample from Dijon, France, 1,440 participants aged 65-80 years (median age: 72 years; 59.5% women) without depression, dementia, or stroke at baseline were studied. Baseline T2-weighted images were obtained in a 1.5-T scanner to quantify WMHs (log cm(3)). Clinic visits were performed up to five times in a 10-year period to assess incident neurologic diseases and comorbidities. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale and converted to factor z scores, representing somatic symptoms, depressed affect, low positive affect, and interpersonal problems. RESULTS: Periventricular WMH volume was uniquely associated with low positive affect among incident depression cases (beta = 0.15; 95% confidence interval [CI]: 0.02-0.29; p = 0.026). Deep WMH volume was uniquely associated with depressed affect among incident dementia cases (beta = 0.36; 95% CI: 0.05-0.68; p = 0.025). WMH volume (periventricular, deep, and total) was associated with interpersonal problems among persons who developed dementia with depression. CONCLUSION: The findings highlight that regional WMH volumes and specific depressive symptoms have clinical and prognostic relevance to help differentiate between persons at risk for depression and dementia.",Depression;cerebrovascular disease;dementia;geriatric psychiatry;longitudinal;white matter hyperintensity,"Tully, P. J.;Debette, S.;Mazoyer, B.;Tzourio, C.",2017,Dec,,0,
722,White matter diffusion is higher in Binswanger disease than in idiopathic normal pressure hydrocephalus,"OBJECTIVES: To explore diagnostic differences in periventricular white matter (PWM) and deep white matter (DWM) diffusion patterns in patients diagnosed with Binswanger disease (BD) and in patients diagnosed with probable idiopathic normal pressure hydrocephalus (INPH) using diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) values were calculated in the PWM and DWM in patients with INPH (n = 14) and BD (n = 9) and in controls (n = 10) using an spin echo echo planar imaging single-shot diffusion sequence and region of interest (ROI) analysis. RESULTS: Patients with BD had higher ADC values than patients with INPH in the PWM and DWM in the frontal and occipital regions (P < 0.05) and higher values than controls in the frontal PWM and DWM (P < 0.01). After shunt surgery, ADC values were reduced in the frontal PWM in patients with INPH (P < 0.05). CONCLUSIONS: Increased diffusion in the PWM and DWM in patients with BD may reflect irreversible breakdown of axonal integrity caused by the subcortical ischaemic vascular disease. By contrast, the normal white matter diffusion in patients with INPH indicates structurally intact axons, compatible with the reversibility of this disorder. DWI may be an important non-invasive diagnostic tool for differentiating between INPH and BD and identifying shunt responders and reversible brain damage in patients with INPH. However, the overlap between patients with INPH and BD in this study restricts the predictive value of the method.","Aged;Aged, 80 and over;Dementia, Vascular/ pathology;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Hydrocephalus, Normal Pressure/ pathology;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Regression Analysis","Tullberg, M.;Ziegelitz, D.;Ribbelin, S.;Ekholm, S.",2009,Oct,10.1111/j.1600-0404.2009.01165.x,0,
723,"White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity, predictive value and correlations to axonal degeneration and demyelination","OBJECTIVES: To analyse the diagnostic and prognostic value of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) magnetic resonance imaging (MRI) changes and their relation to symptoms and cerebrospinal fluid (CSF) markers of demyelination (sulphatide) and axonal degeneration [neurofilament triplet protein (NFL)] in a large series of patients with normal pressure hydrocephalus (NPH) and Binswanger disease (BD). MATERIALS AND METHODS: PVH and DWMH were determined by a semi-automatic segmentation method on T2-weighted images in 29 patients with NPH and 17 patients with BD. CSF analyses, psychometric testing and quantification of balance, gait and continence were performed in all patients and also postoperatively in NPH patients. RESULTS: No MRI variable could identify NPH or BD patients. Abundant PVH and DWMH preoperatively correlated with improvement in gait, balance and psychometric performance after shunt surgery (P < 0.05). CSF sulphatide correlated positively with the amount of DWMH (P < 0.05) while NFL was correlated to both PVH and DWMH (P < 0.05). Abundant PVH correlated with poor psychometric performance while DWMH correlated with gait disturbance (P < 0.05). Postoperative reduction in PVH correlated with improvement in gait, balance and psychometric performance. CONCLUSION: In spite of a refined quantification method, NPH and BD patients exhibited similar MRI changes. MRI had a predictive value in NPH patients. DWMH might relate to demyelination and PVH to neuronal axonal dysfunction. NPH and BD share the major part of symptoms and MRI changes, indicating a common pathophysiological pattern, and we raise the question of how to treat BD patients.","Aged;Aged, 80 and over;Axons/ pathology;Dementia, Vascular/cerebrospinal fluid/ pathology;Demyelinating Diseases/cerebrospinal fluid/ pathology;Female;Humans;Hydrocephalus, Normal Pressure/cerebrospinal fluid/ pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Sulfoglycosphingolipids/cerebrospinal fluid","Tullberg, M.;Hultin, L.;Ekholm, S.;Mansson, J. E.;Fredman, P.;Wikkelso, C.",2002,Jun,,0,
724,White matter lesions impair frontal lobe function regardless of their location,"Objective: To analyze the effect of white matter lesions in different brain regions on regional cortical glucose metabolism, regional cortical atrophy, and cognitive function in a sample with a broad range of cerebrovascular disease and cognitive function. Methods: Subjects (n = 78) were recruited for a study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD) contributions to dementia. A new method was developed to define volumes of interest from high-resolution three-dimensional T1-weighted MR images. Volumetric measures of MRI segmented white matter signal hyperintensities (WMH) in five different brain regions were related to regional PET glucose metabolism (rCMRglc) in cerebral cortex, MRI measures of regional cortical atrophy, and neuropsychological assessment of executive and memory function. Results: WMH was significantly higher in the prefrontal region compared to the other brain regions. In all subjects, higher frontal and parietal WMH were associated with reduced frontal rCMRglc, whereas occipitotemporal WMH was only marginally associated with frontal rCMRglc. These associations were stronger and more widely distributed in nondemented subjects where reduced frontal rCMRglc was correlated with WMH for all regions measured. In contrast, there was no relationship between WMH in any brain region and rCMRglc in either parietal or occipitotemporal regions. WMHs in all brain regions were associated with low executive scores in nondemented subjects. Conclusions: The frontal lobes are most severely affected by SIVD. WMHs are more abundant in the frontal region. Regardless of where in the brain these WMHs are located, they are associated with frontal hypometabolism and executive dysfunction.",,"Tullberg, M.;Fletcher, E.;DeCarli, C.;Mungas, D.;Reed, B. R.;Harvey, D. J.;Weiner, M. W.;Chui, H. C.;Jagust, W. J.",2004,27,,0,
725,Structural network efficiency predicts conversion to dementia,"OBJECTIVE: To examine whether structural network connectivity at baseline predicts incident all-cause dementia in a prospective hospital-based cohort of elderly participants with MRI evidence of small vessel disease (SVD). METHODS: A total of 436 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC), a prospective hospital-based cohort of elderly without dementia with cerebral SVD, were included in 2006. During follow-up (2011-2012), dementia was diagnosed. The structural network was constructed from baseline diffusion tensor imaging followed by deterministic tractography and measures of efficiency using graph theory were calculated. Cox proportional regression analyses were conducted. RESULTS: During 5 years of follow-up, 32 patients developed dementia. MRI markers for SVD were strongly associated with network measures. Patients with dementia showed lower total network strength and global and local efficiency at baseline as compared with the group without dementia. Lower global network efficiency was independently associated with increased risk of incident all-cause dementia (hazard ratio 0.63, 95% confidence interval 0.42-0.96, p = 0.032); in contrast, individual SVD markers including lacunes, white matter hyperintensities volume, and atrophy were not independently associated. CONCLUSIONS: These results support a role of network disruption playing a pivotal role in the genesis of dementia in SVD, and suggest network analysis of the connectivity of white matter has potential as a predictive marker in the disease.",,"Tuladhar, A. M.;van Uden, I. W.;Rutten-Jacobs, L. C.;Lawrence, A.;van der Holst, H.;van Norden, A.;de Laat, K.;van Dijk, E.;Claassen, J. A.;Kessels, R. P.;Markus, H. S.;Norris, D. G.;de Leeuw, F. E.",2016,Mar 22,10.1212/wnl.0000000000002502,0,
726,White matter integrity in small vessel disease is related to cognition,"Cerebral small vessel disease, including white matter hyperintensities (WMH) and lacunes of presumed vascular origin, is common in elderly people and is related to cognitive impairment and dementia. One possible mechanism could be the disruption of white matter tracts (both within WMH and normal-appearing white matter) that connect distributed brain regions involved in cognitive functions. Here, we investigated the relation between microstructural integrity of the white matter and cognitive functions in patients with small vessel disease. The Radboud University Nijmegen Diffusion tensor and Magnetic resonance Cohort study is a prospective cohort study among 444 independently living, non-demented elderly with cerebral small vessel disease, aged between 5500 and 85 years. All subjects underwent magnetic resonance imaging and diffusion tensor imaging scanning and an extensive neuropsychological assessment. We showed that loss of microstructural integrity of the white matter at specific locations was related to specific cognitive disturbances, which was mainly located in the normal-appearing white matter (p < 0.05, FWE-corrected for multiple comparisons). The microstructural integrity in the genu and splenium showed the highest significant relation with global cognitive function and executive functions, in the cingulum bundle with verbal memory performance. Associations between diffusion tensor imaging parameters and most cognitive domains remained present after adjustment for WMH and lacunes. In conclusion, cognitive disturbances in subjects with cerebral small vessel disease are related to microstructural integrity of multiple white matter fibers (within WMH and normal-appearing white matter) connecting different cortical and subcortical regions.","Aged;Aged, 80 and over;Brain/blood supply/ pathology;Cerebral Small Vessel Diseases/complications/ pathology;Cognition Disorders/etiology/ pathology;Cohort Studies;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology","Tuladhar, A. M.;van Norden, A. G.;de Laat, K. F.;Zwiers, M. P.;van Dijk, E. J.;Norris, D. G.;de Leeuw, F. E.",2015,,10.1016/j.nicl.2015.02.003,0,
727,"Relationship between white matter hyperintensities, cortical thickness, and cognition","BACKGROUND AND PURPOSE - : White matter hyperintensities (WMH) are associated with clinically heterogeneous symptoms that cannot be explained by these lesions alone. It is hypothesized that these lesions are associated with distant cortical atrophy and cortical thickness network measures, which can result in an additional cognitive impairment. Here, we investigated the relationships between WMH, cortical thickness, and cognition in subjects with cerebral small vessel disease. METHODS - : A total of 426 subjects with cerebral small vessel disease were included, aged between 50 and 85 years, without dementia, and underwent MRI scanning. Cortical thickness analysis was performed, and WMH were manually segmented. Graph theory was applied to examine the relationship between network measures and WMH, and structural covariance matrices were constructed using inter-regional cortical thickness correlations. RESULTS - : Higher WMH load was related to lower cortical thickness in frontotemporal regions, whereas in paracentral regions, this was related to higher cortical thickness. Network analyses revealed that measures of network disruption were associated with WMH and cognitive performance. Furthermore, WMH in specific white matter tracts were related to regional-specific cortical thickness and network measures. Cognitive performances were related to cortical thickness in frontotemporal regions and network measures, and not to WMH, while controlling for cortical thickness. CONCLUSIONS - : These cross-sectional results suggest that cortical changes (regional-specific damage and network breakdown), mediated (in)directly by WMH (tract-specific damage) and other factors (eg, vascular risk factors), might lead to cognitive decline. These findings have implications in understanding the relationship between WMH, cortical morphology, and the possible attendant cognitive decline and eventually dementia.",adult;aged;article;body mass;cerebrovascular disease;cognition;controlled study;cortical thickness (brain);dementia;diabetes mellitus;disease severity;female;human;hypercholesterolemia;hypertension;major clinical study;male;Mini Mental State Examination;morphology;neuroimaging;nuclear magnetic resonance imaging;posterior cingulate;priority journal;risk factor;smoking;white matter,"Tuladhar, A. M.;Reid, A. T.;Shumskaya, E.;De Laat, K. F.;Van Norden, A. G. W.;Van Dijk, E. J.;Norris, D. G.;De Leeuw, F. E.",2014,,,0,
728,Efficacy of gadolinium in MR brain imaging of HIV-infected patients,"PURPOSE: To determine the value of gadolinium in routine head MR imaging of HIV-infected patients. METHODS: One hundred and three consecutive human immunodeficiency virus-infected patients referred for head MR imaging were scanned without and with intravenous gadopentetate dimeglumine (Gd-DTPA) contrast. RESULTS: The precontrast scans of 82 patients were either normal, or had atrophy or diffuse white matter changes only. Sixteen of these 82 demonstrated enhancing abnormalities: eight meningeal/ependymal enhancement and eight focal enhancing lesions. Twenty-one of the 103 scans had focal or mass lesions on the precontrast images; in eight of these scans, new information was obtained with Gd-DTPA. Of the 24 patients in both groups where new information was obtained with Gd-DTPA, the information contributed to a change in the clinical care of nine patients. CONCLUSION: Gadolinium-enhanced MR is useful in the management of selected patients with human immunodeficiency virus infection, for example those with symptoms suggesting meningeal involvement, focal brain lesions, or if the unenhanced MR does not explain all the patient's symptoms.",AIDS Dementia Complex/diagnosis;AIDS-Related Opportunistic Infections/diagnosis;Adult;Brain Diseases/complications/ diagnosis;Contrast Media;Female;Gadolinium DTPA;HIV Infections/ complications;Humans;Magnetic Resonance Imaging;Male;Organometallic Compounds;Pentetic Acid,"Tuite, M.;Ketonen, L.;Kieburtz, K.;Handy, B.",1993,Jan-Feb,,0,
729,Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism,"Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39–240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35–100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.",phenylalanine;adult;apraxia;article;blurred vision;case report;cerebrospinal fluid examination;Clinical Dementia Rating;dementia;diffusion weighted imaging;electroencephalography;gait disorder;human;male;middle aged;Mini Mental State Examination;parkinsonism;phenylketonuria;pyramidal sign;theta rhythm,"Tufekcioglu, Z.;Cakar, A.;Bilgic, B.;Hanagasi, H.;Gurvit, H.;Emre, M.",2016,,10.1080/13554794.2016.1142567,0,730
730,Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism,"Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 mumol/L, normal 39-240 mumol/L) with normal tyrosine level (61.20 mumol/L, normal 35-100 mumol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.",,"Tufekcioglu, Z.;Cakar, A.;Bilgic, B.;Hanagasi, H.;Gurvit, H.;Emre, M.",2016,Mar 10,10.1080/13554794.2016.1142567,0,
731,Structural Connectivity Alterations Along the Alzheimer's Disease Continuum: Reproducibility Across Two Independent Samples and Correlation with Cerebrospinal Fluid Amyloid-beta and Tau,"BACKGROUND: Gray matter changes associated with the progression of Alzheimer's disease (AD) have been thoroughly studied. However, alterations in white matter tracts have received less attention, particularly during early or preclinical stages of the disease. OBJECTIVE: To identify the structural connectivity changes across the AD continuum. METHODS: We performed probabilistic tractography in a total of 183 subjects on two independent samples that include control (n = 68) and preclinical AD individuals (n = 28), patients diagnosed with mild cognitive impairment (MCI) due to AD (n = 44), and AD patients (n = 43). We compared the connectivity between groups, and with CSF Abeta42 and tau biomarkers. RESULTS: We observed disconnections in preclinical individuals, mainly located in the temporal lobe. This pattern of disconnection spread to the parietal and frontal lobes at the MCI stage and involved almost all the brain in AD. These findings were not driven by gray matter atrophy. DISCUSSION: Using tractography, we were able to identify white matter changes between subsequent disease stages and, notably, also in preclinical AD. Therefore, this method may be useful for detecting early and specific brain structural changes during preclinical AD stage.",Alzheimer's disease;biomarkers;connectivity;diffusion MRI;magnetic resonance imaging;mild cognitive impairment;preclinical stage;tractography,"Tucholka, A.;Grau-Rivera, O.;Falcon, C.;Rami, L.;Sanchez-Valle, R.;Llado, A.;Gispert, J. D.;Molinuevo, J. L.;Alzheimer's Disease Neuroimaging, Initiative",2018,,,0,
732,"Bilateral thalamic infarction: Clinical, etiological and mri correlates","To determine clinical, behavioral, topographic and etiological patterns in patients with simultaneous bilateral thalamic infarction in varied thalamic artery territories, we studied 16 patients who were admitted to our stroke unit over a 7-year period. Patients with bithalamic infarction represented 0.6% of our registry which included 2750 ischaemic stroke patients. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were 4 topographic patterns of infarction: 1) bilateral infarcts in the territory of paramedian artery (8 patients [50%]); 2) bilateral infarcts in the territory of thalamogeniculate arteries (3 patients [19%]); 3) bilateral infarcts involving territory of paramedian and thalamogeniculate arteries (3 patients [19%]); 4) bilateral infarcts involving territory of polar and thalamogeniculate arteries (2 patients [13%]). A specific clinical picture was found in up to 50% of the patients with bithalamic infarction. This included patients with bilateral paramedian infarction having disorder of consciousness, memory dysfunctions, various types of vertical gaze palsy and psychic changes. Bilateral sensory loss predicted accurately bilateral infarction in the territory of thalamogeniculate arteries. The main cause of bilateral thalamic infarction was small artery-disease, followed by cardioembolism. Cognitive functions in patients with bilateral paramedian infarction did not change significantly during the follow-up, in contrast to those with infarcts in varied arterial territories. Acute bilateral infarction involving both thalamus is uncommon, although they are often associated with specific neurologic-neuropsychological patterns, allowing diagnosis before radiological examination.",,"Tucha, O.;Naumann, M.;Berg, D.;Alders, G. L.;Lange, K. W.",2001,2001,,0,
733,Divergent Longitudinal Propagation of White Matter Degradation in Logopenic and Semantic Variants of Primary Progressive Aphasia,"BACKGROUND: Clinico-pathological distinction of primary progressive aphasia (PPA) can be challenging at clinic presentation. In particular, cross-sectional neuroimaging signatures across the logopenic (lvPPA) and semantic (svPPA) variants are difficult to establish, with longitudinal profiles showing greater divergence. OBJECTIVE: Assess longitudinal propagation of white matter degradation in lvPPA and svPPA to determine disease progression over time, and whether this reflects distinct underlying pathology. METHOD: A cohort of 27 patients with dementia (12 lvPPA; 15 svPPA) and 12 healthy controls were assessed at baseline and 1-year follow-up on the Addenbrooke's Cognitive Examination-Revised and Sydney Language Battery. Diffusion weighted images were collected at both time-points and analyzed for longitudinal white matter change using DTI-TK and TBSS. RESULTS: LvPPA patients showed a significant decline in naming and repetition, over 1 year, while svPPA patients declined in naming and comprehension. Longitudinal imaging revealed widespread bilateral degradation of white matter tracts in lvPPA over a 1-year period with early involvement of the left posterior inferior longitudinal fasciculus (ILF). SvPPA demonstrated focal left lateralized white matter degradation involving the uncinate fasciculus (UF) and anterior ILF, propagating to the right UF with disease progression. CONCLUSIONS: LvPPA and svPPA cohorts showed distinct longitudinal cognitive and white matter profiles. We propose differences in multi-centric and focal white matter dysfunction in lvPPA and svPPA, respectively, reflect underlying pathological differences. The clinical relevance of white matter degradation and mechanisms underlying disease propagation are discussed.",,"Tu, S.;Leyton, C. E.;Hodges, J. R.;Piguet, O.;Hornberger, M.",2015,Oct 17,10.3233/jad-150626,0,
734,Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer's disease,"BACKGROUND: The causes of behavioral and psychological symptoms of dementia (BPSD) vary according to the dementia subtype and associated neuropathology. The present study aimed to (i) compare BPSD between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) across stages, and (ii) explore the associations with diffusion tensor imaging (DTI) in the corpus callosum (CC) and other major fibers. METHODS: Twenty-four patients with SIVD and 32 with AD were recruited. Four domains of the Neuropsychiatric Inventory (NPI) (hyperactivity, psychosis, affective, and apathy) and two DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] within the genu, body (BCC), and splenium (SCC) of the CC and other major fibers were assessed. RESULTS: Overall, the patients with clinical dementia rating (CDR) 1 ~ 2 had higher scores in apathy domain than those with CDR0.5. Among those with CDR1 ~ 2, SIVD had higher scores in apathy domain than AD. MD values in the BCC/SCC were positively correlated with total NPI score and psychosis, hyperactivity, and apathy domains. FA values in the SCC were inversely correlated with total NPI score and psychosis domain. The correlations were modified by age, the CASI, and CDR scores. Stepwise linear regression models suggested that FA value within the left superior longitudinal fasciculus predicted the hyperactivity domain. MD value within the SCC/left uncinate fasciculus and FA value within the GCC/left forceps major predicted the psychosis domain. MD value within the right superior longitudinal fasciculus and CDR predicted the apathy domain. Further analysis suggested distinct patterns of regression models between SIVD and AD patients. CONCLUSION: White matter integrity within the BCC/SCC had associations with multi-domains of BPSD. Our study also identified important roles of regions other than the CC to individual domain of BPSD, including the left superior longitudinal fasciculus to the hyperactivity domain, the left uncinate fasciculus/forceps major to the psychosis domain, and the right superior longitudinal fasciculus to the apathy domain. The neuronal substrates in predicting BPSD were different between SIVD and AD patients. Of note, apathy, which was more profound in SIVD, was associated with corresponding fiber disconnection in line with dementia severity and global cognition decline.",Alzheimer's disease;Apathy;Behavioral and psychological symptoms of dementia;Corpus callosum;Diffusion tensor imaging;Neuropsychiatric inventory;Psychosis;Subcortical ischemic vascular disease,"Tu, M. C.;Huang, W. H.;Hsu, Y. H.;Lo, C. P.;Deng, J. F.;Huang, C. F.",2017,Jul 28,,0,
735,Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6 months follow-up period,"PURPOSE: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD) and may contribute to cognitive impairment. Plasma total homocysteine (tHcy) had also been linked with cognitive decline in AD. We examined the relationship among change of cognition, tHcy level, and WMHs on MRI in AD patients with a follow-up periods of 6 months. METHODS: AD patients with normal creatinine level and initial clinical dementia rating (CDR) of 1 to 2 were enrolled. tHcy and biochemistry tests related to cerebral vascular risk factors were collected. WMHs were measured on MRI fluid attenuated inverse recovery sequence and classified into deep white matter hyperintensities (DWMHs) and periventricular white matter hyperintensities (PWMHs) by visual rating scale. Neuropsychological tests including cognitive ability screening instrument (CASI), mini-mental state examination (MMSE) converted from CASI scores and CDR were collected twice during the follow- up period of 6 months. RESULTS: Ninety-two AD patients, 30 men and 62 women completed the study while the tHcy level was not significantly different between AD and age matched controls. tHcy level showed no correlation with CASI or MMSE score, at either the first or second examination. tHcy showed positive correlation with decline of CASI total score and abstract thinking (both p<0.01) but not in MMSE decline. There was no significant correlation between neuropsychiatric assessment and WMHs, but the decline of abstract thinking score was related to frontal PWMHs (R square=0.237, p=0.007). CONCLUSION: tHcy might be associated with rapid cognitive decline in AD after a 6-month follow-up period and the effect might not be directly through WMHs. tHcy level correlated with greater WMHs in the trigone area although greater lesion load by MRI was in the occipital lobe.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ complications;Case-Control Studies;Cognition Disorders/ complications;Female;Follow-Up Studies;Homocysteine/blood;Humans;Hyperhomocysteinemia/diagnosis/ etiology;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Retrospective Studies","Tu, M. C.;Huang, C. W.;Chen, N. C.;Chang, W. N.;Lui, C. C.;Chen, C. F.;Chen, C.;Wang, Y. L.;Lin, Y. T.;Chang, C. C.",2010,Sep,,0,
736,A common mutation and a novel mutation in Japanese patients with van der Knaap disease,"Van der Knaap disease, or megalencephalic leukoencephalopathy with subcortical cysts (MLC), is an autosomal recessive disorder clinically characterized by macrocephaly, ataxia, spasticity, and mental decline. Magnetic resonance imaging (MRI) shows swollen brain with diffuse white-matter abnormalities and subcortical cysts, particularly in the anterior-temporal region. Recently, the MLC1 gene was identified as the gene responsible for this disorder, and mutations in this gene were described in several patients. We studied three Japanese patients with van der Knaap disease at the molecular genetic level. Two of them were homozygous for a previously-described mutation, S93L, and one was a compound heterozygote for S93L and a novel mutation, 452-468del+g, which leads to frameshift with a premature termination codon. Combining our data with previous reports allowed us to estimate the molecular genetic basis of this disorder in seven Japanese patients. In summary, S93L was observed in six of seven (85.7%) patients at least in one allele, and ten of 14 (71.4%) alleles had this mutation. Therefore, S93L appears to be fairly frequent in Japanese patients with van der Knaap disease, and analysis for this mutation in DNA isolated from leukocytes would provide for an easy and precise diagnosis of this disorder in Japanese patients.","Adult;Alleles;Brain/pathology;Brain Diseases/ genetics/ pathology;Codon;Consanguinity;DNA Mutational Analysis;DNA, Complementary/metabolism;Dementia, Vascular/genetics/pathology;Family Health;Female;Genes, Recessive;Heterozygote;Homozygote;Humans;Japan;Magnetic Resonance Imaging;Male;Membrane Proteins/ genetics;Mutation;Reverse Transcriptase Polymerase Chain Reaction","Tsujino, S.;Kanazawa, N.;Yoneyama, H.;Shimono, M.;Kawakami, A.;Hatanaka, Y.;Shimizu, T.;Oba, H.",2003,,10.1007/s10038-003-0085-4,0,
737,Effectiveness of midazolam for L-arginine-resistant headaches during stroke-like episodes in MELAS: A case report,"A 14-year-old girl was referred to us with severe migraine-like headaches associated with vomiting and right homonymous hemianopsia. On admission, MRI examination showed high signals in the left occipital cortex and subcortex on T2-weighted images, without reduction of apparent diffusion coefticient suggestive of cerebral infarction. Her EEG demonstrated periodic sharp waves in the left posterior region, and laboratory tests revealed she had increased levels of lactic and pyruvic acid both in blood plasma and CSF. Gene analysis confirmed mitochondrial DNA A3243G mutation. Based on this data, we diagnosed her as having mitochondrial myopathy, encephalopathy, lactic acidosis and a stroke-like episode (MELAS). L-arginine infusion was unsuccessful for her severe headaches, which remained prolonged, ^he received a low dose (0.05 mg/kg/h) midazolam infusion, resulting in immediate improvement and the disappearance of headaches and abnormal EEG findings. By the age of 18, she had been readmitted eight times for stroke-like episodes accompanied by headaches. While L-arginine infusions alleviated her headaches when administered on day 1 of her episodes, they were not effective when started on or after day 2. Her L-arginine-resistant headaches were relieved by midazolam. Although the pathogenesis of headaches in MELAS is still unknown, neuronal hyperexcitability and trigeminovascular activation are considered important. Midazolam may play a role in suppressing neuronal hyperexcitability and trigeminovascular activation. Treatment with midazolam is advisable for headaches in patients with MELAS, in the event that L-arginine therapy is unsuccessful.",,"Tsujikawa, K.;Yokoi, S.;Yasui, K.;Hasegawa, Y.;Hoshiyama, M.;Yanagi, T.",2014,2014,,0,
738,Epidemiological and neurophysiological studies in Creutzfeldt-Jakob disease,"The prevalence rate of Creutzfeldt-Jakob disease (CJD) in Japan was one per one million population. The average age of onset was 56 years ranging between 25 and 77 years. The mean duration of CJD course was 16.6 months. The neurological signs in 63 CJD cases were dementia (98%), abnormal posture (92%), myoclonus (92%), extrapyramidal signs (91%), akinetic mutism (90%), pyramidal signs (85%), cerebellar signs (51%) and muscular atrophies of extremities (44%). Seven cases of CJD with extensive white matter involvements showed similar neurological findings except for a slightly longer duration (mean duration 2.8 years) in comparison with the results of a nation-wide survey of CJD in Japan. The periodic synchronous discharge (PSD) was a diagnostic finding in CJD. The progression of cerebral atrophy was noted by serial CT scan examinations. The CSF examinations were normal in most of cases. Giant cerebral evoked potentials were seen by somatosensory, visual and auditory evoked potential studies. However, short latency somatosensory and auditory brainstem evoked potentials were normal. These results were compatible with almost normal clinical brainstem function in CJD. The motor potential of the thumb was generated after the median nerve stimulation with the latency of 43.6 msec. This response resembles the long loop reflex which was seen in myoclonic epilepsy.",central nervous system;Creutzfeldt Jakob disease;diagnosis;epidemiology;evoked response;major clinical study,"Tsuji, S.",1981,,,0,
739,Intravascular lymphomatosis manifesting clinically as subacute encephalopathy,"We report a 62-year-old woman with intravascular lymphomatosis (IVL) which presented as subacute encephalopathy. She was admitted to our hospital because of loss of consciousness in the middle of February, 2006. Laboratory tests indicated elevated serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed multiple infarct-like lesions mainly in the white matter. After admission, her consciousness was soon improved, but the inflammatory response did not disappear with any antibiotics or virucides. Her consciousness was not exacerbated, and she was discharged in the middle of March, although the reason for loss of consciousness remained unknown. After discharge she developed an abnormal behavior and mental deterioration, and therefore she was readmitted late in March. On second admission, her consciousness was drowsy. Neurological examinations revealed conjugate deviation of her eyes to the left, left hemiparesis, and generalized hyporeflexia. Laboratory tests showed more elevated CRP than that of the last time, and raised soluble IL-2 receptor (sIL-2R). The repeated MRI of the brain disclosed that initial lesions of the white matter progressively enlarged and increased in number. To make an appropriate diagnosis of the lesions on the brain MRI, the open brain biopsy was performed. Microscopic examination showed that many small vessels were occluded by lymphoma cells (B-lymphocytes) with hemorrhage, and IVL was diagnosed. She was treated with regimens of combined chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). After chemotherapy her consciousness and left hemiparesis were gradually improved and the levels of CRP were normalized. The infarcts-like lesions detected on the brain MRI became reduced and decreased. IVL is a rare disease, and the prognosis is generally poor, with a rapidly fatal outcome, leading to a postmortem diagnosis. In the present report, we successfully treated the patient by rituximab in addition to standard CHOP therapy. Rituximab may play an important role in the treatment of IVL.",,"Tsuji, H.;Mochiduki, A.;Hosaka, A.;Yoshizawa, T.;Tamaoka, A.",2008,May,,0,
740,[Brain water diffusion coefficients and diffusion anisotropy in non-demented patients with diffuse leuko-araiosis],"PURPOSE: To investigate changes in both water diffusion coefficients and diffusion anisotropy in white matter of non-demented patients with leuko-araiosis using diffusion-weighted MRI. METHODS: Diffusion mapping was performed on 8 non-demented patients with leuko-araiosis, 6 patients with chronic cerebral infarction and 6 healthy volunteers, using a spin-echo sequence with motion probing gradient applied sequentially at two gradient strength settings in three orthogonal directions. The apparent diffusion coefficients (ADC) were calculated from 4 regions of interest located within the frontal and parietal subcortical white matter. The index of diffusion anisotropy (IDA) was calculated from the ADC in three orthogonal directions. (IDA = ADCmax-min/ADCmean x 100). RESULTS: Significantly larger ADC were found within the frontal and parietal subcortical white matter in the non-demented patients with leuko-araiosis (mean = 1.51 +/- 0.36 x 10(-3) mm2/s) and the were also significantly larger in patients with cerebral infarction (mean = 2.12 +/- 0.46 x 10(-3) mm2/s) than in the control group (mean = 1.01 +/- 0.33 x 10(-3) mm2/s). But no significant differences were found in the IDA between the non-demented patients with leuko-araiosis (mean = 43.1 +/- 29.2) and the control group (mean = 46.5 +/- 32.5). CONCLUSION: An increase in extracellular space caused by the loss of axonal fibers and myelin is probably the cause of the higher ADC in periventricular hyperintensity lesions. However, the remaining nerve fibers maintain the anisotropy in the lesions in non-demented patients with leuko-araiosis.","Aged;Anisotropy;Body Water/*metabolism;Brain/*metabolism/*pathology;Cerebral Infarction/diagnosis/metabolism/pathology;Dementia, Vascular/*diagnosis/metabolism/pathology;Diagnosis, Differential;Diffusion;Humans;Image Enhancement/methods;Magnetic Resonance Imaging/*methods;Middle Aged","Tsuganesawa, T.;Igarashi, H.;Kitamura, S.;Terashi, A.",1998,Apr,,0,
741,Cortical blood flow and cognition after extracranial-intracranial bypass in a patient with severe carotid occlusive lesions - A three-year follow-up study,"The long-term effect of extra-intracranial arterial bypass on cerebral circulation was examined. Cortical blood flow and cognitive ability were evaluated pre- and up to 3 years post-bypass in a 58-years-old man with severe carotid occlusive lesions, who presented with 3 transient cerebral ischaemic attacks which resulted in mental deterioration over 3 years. Regional cerebral blood flow (rCBF) was evaluated pre- and up to 33 months post-bypass by 123Iodine N-isopropyl-p-iodoamphetamine (IMP) single-photon emission CT (SPECT). Mental abilities were evaluated before and up to 33 months after surgery by the Hasegawa's dementia rating scale (HDRS). Pre-operatively, cerebral angiography showed left carotid siphon occlusion and hypoplastic stenosis of left anterior cerebral artery with collaterals from the anterior communicating artery. CT and MRI showed left temporo-parietal borderzone infarction and an enhanced T1 lesion by gadolinium-DTPA at left periventriculum. rCBF showed extensive hypoperfusion in left anterior-parieto-temporal-cortex. HDRS scores deteriorated apparently on days 3, 5, which recovered gradually on days 8, 10, 75 after onset of mental deterioration. A bypass was performed 4 months after onset. rCBF showed gradual recovery in the left anterior-parietal cortex up to 33 months after bypass. Semiquantitative rCBF showed gradual decreases of regional asymmetry after the bypass. HDRS scores returned to their maximum up to 37 months after onset. Three-year follow-up shows improved cortical rCBF and cognition after the bypass.",gadolinium pentetate albumin;iofetamine i 123;adult;anterior cerebral artery;anterior communicating artery;article;brain angiography;brain blood flow;brain cortex;brain infarction;brain ischemia;brain tomography;bypass surgery;carotid artery obstruction;case report;cognition;contrast enhancement;follow up;human;male;mental deterioration;nuclear magnetic resonance imaging;parietal lobe;preoperative evaluation;priority journal;rating scale;single photon emission computer tomography;temporal cortex,"Tsuda, Y.;Yamada, K.;Hayakawa, T.;Ayada, Y.;Kawasaki, S.;Matsuo, H.",1994,,,0,
742,Lacunar Infarcts Rather than White Matter Hyperintensity as a Predictor of Future Higher Level Functional Decline: The Ohasama Study,"Objective We aimed to determine the associations between silent cerebrovascular lesions, characterized by lacunar infarcts and white matter hyperintensity, and future decline in higher level functional capacity in older community-dwelling adults. Materials and Methods For this observational study, we selected individuals from the general population of Ohasama, a rural Japanese community. Three hundred thirty-one participants who were free of functional decline at baseline and who were at least 60 years old underwent brain magnetic resonance imaging and answered a questionnaire on higher level functional capacity derived from the Tokyo Metropolitan Institute of Gerontology Index of Competence. Weassessed the relationship between silent cerebrovascular lesions with a decline in higher level functional capacity at 7 years using multiple logistic regression analysis adjusted for possible confounding factors. Results During the follow-up, 22.1% reported declines in higher level functional capacity. After adjustment for putative confounding factors, the presence of silent cerebrovascular lesions (odds ratio [95% confidence interval], 2.10 [1.05-4.21]) and both lacunar infarcts (2.04 [1.05-3.95]) and white matter hyperintensity (2.02 [1.02-3.95]) was significantly associated with the risk of functional decline at 7-year follow-up. In subscale analysis, specifically lacunar infarcts were strongly associated with the future risk of decline in intellectual activity (3.16 [1.27-7.84]). Conclusion Silent cerebrovascular lesions are associated with future risk of decline in higher level functional capacity. Appropriate management of health risk factors to prevent silent cerebrovascular lesions may prevent higher level functional decline in the elderly population.",ADL disability;aged;article;body mass;cerebrovascular accident;diabetes mellitus;female;follow up;functional disease;functional status;gerontology;human;hypercholesterolemia;hypertension;Japan;lacunar stroke;major clinical study;male;mental deterioration;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;observational study;prediction;priority journal;sleep time;transient ischemic attack;white matter lesion,"Tsubota-Utsugi, M.;Satoh, M.;Tomita, N.;Hara, A.;Kondo, T.;Hosaka, M.;Saito, S.;Asayama, K.;Inoue, R.;Hirano, M.;Hosokawa, A.;Murakami, K.;Murakami, T.;Metoki, H.;Kikuya, M.;Izumi, S. I.;Imai, Y.;Ohkubo, T.",2017,,10.1016/j.jstrokecerebrovasdis.2016.09.036,0,
743,Clinical and neuroimaging correlates of abnormal short-latency Somatosensory Evoked Potentials in elderly vascular dementia patients: A psychophysiological exploratory study,"BACKGROUND: Short Latency Somatosensory Evoked Potentials (SEPs) may serve to the testing of the somatosensory tract function, which is vulnerable and affected in vascular encephalopathy. The aim of the current study was to search for clinical and neuroimaging correlates of abnormal SEPs in vascular dementia (VD) patients. MATERIALS AND METHODS: The study included 14 VD patients, aged 72.93 PlusMinus; 4.73 years, and 10 controls aged 71.20 PlusMinus; 4.44 years. All subjects underwent a detailed clinical examination, blood and biochemical testing, brain MRI and were assessed with the MMSE. SEPs were recorded after stimulation from upper and lower limbs. The statistical Analysis included 1 and 2-way MANCOVAs and Factor analysis RESULTS: The N13 latency was significantly prolonged, the N19 amplitude was lower, the P27 amplitude was lower and the N11-P27 conduction time was prolonged in severely demented patients in comparison to controls. The N19 latency was prolonged in severely demented patients in comparison to both mildly demented and controls. The same was true for the N13-N19 conduction time, and for the P27 latency. Patients with subcortical lesions had all their latencies prolonged and lower P27 amplitude. DISCUSSION: The results of the current study suggest that there are significant differences between patients suffering from VD and healthy controls in SEPs, but these are detectable only when dementia is severe or there are lesions located in the subcortical regions. The results of the current study locate the abnormal SEPs in the white matter, and are in accord with the literature.",,"Tsiptsios, I.;Fountoulakis, K. N.;Sitzoglou, K.;Papanicolaou, A.;Phokas, K.;Fotiou, F.;St Kaprinis, G.",2003,Sep 5,10.1186/1475-2832-2-8,0,
744,Intracerebral hemorrhage: An unusual presentation of neurosarcoidosis,"Neurosarcoidosis has a variety of clinical presentations. Common manifestations include leptomeningeal inflammation with seizures, headache, cranial nerve palsies, hydrocephalus, or focal neurological deficits with white matter lesions or mass lesions. Stroke is relatively rare, and hemorrhage is much less common than ischemia due to vasculitis. We present a patient with histopathologically confirmed neurosarcoidosis presenting with headache, seizures, and cognitive decline with multiple recurrent primary intracerebral hemorrhages. © 2011 by Lippincott Williams & Wilkins.",corticosteroid;methylprednisolone;prednisone;adult;article;brain biopsy;brain edema;brain hemorrhage;brain vasculitis;case report;cognitive defect;computer assisted tomography;electroencephalogram;focal epilepsy;headache;histopathology;human;low drug dose;magnetic resonance angiography;male;mental deterioration;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;priority journal;psychomotor disorder;sarcoidosis;seizure;sensory dysfunction,"Tsappidi, S.;Hui, F.;Turan, T. N.;Hunter, S.",2011,,,0,
745,The Power of Hybrid/Fusion Imaging Metrics in Future PACS Systems: A Case Study into the White Matter Hyperintensity Prenumbra using FLAIR and Diffusion MR,"Most white matter related neurological disease exhibit a large number of White Matter Hyperintensities (WMHs) on FLAIR MRI images. However, these lesions are not well understood. At the same time, Diffusion MRI has been gaining popularity as a powerful method of characterizing White Matter (WM) integrity. This work aims to study the behavior of the diffusion signal within the WMH voxels. The goal is to develop hybrid MR metrics that leverage information from multiple MR acquisitions to solve clinical problems. In our case, we are trying to address the WMH penumbra (as defined by Maillard et al 20112) where WMH delineates a foci that is more widespread than than the actual damage area presumably due to acute inflammation. Our results show that diffusion MR metrics may be able to better delineate tissue that is inflamed versus scar tissue but may be less specific to lesions than FLAIR. Therefore, a hybrid metric that encodes information from both FLAIR and Diffusion MR may yield new and novel imaging information about the progression of white matter disease progression. We hope that this work also demonstrates how future PACS systems could have image fusion capabilities that would be able to leverage information from multiple imaging series to yield new and novel imaging contrast.",,"Tsao, S.;Ma, S. J.;Michels, P. A.;Gajawelli, N.;Law, M.;Chui, H.;Lepore, N.",2014,Apr 9,10.1117/12.2043921,0,
746,Mapping of ApoE4 Related White Matter Damage using Diffusion MRI,"ApoliopoproteinE epsilon4 (ApoE-epsilon4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE epsilon4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Abeta. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-epsilon4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE epsilon4 allele. We found potentially significant regions (Puncorrected < 0.05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).",Alzheimer's Disease;ApoE;Dti;Dementia;Diffusion MRI;Mri;Neuroimaging,"Tsao, S.;Gajawelli, N.;Hwang, D. H.;Kriger, S.;Law, M.;Chui, H.;Weiner, M.;Lepore, N.",2014,Apr 9,10.1117/12.2043925,0,
747,Relations of arterial stiffness and endothelial function to brain aging in the community,"OBJECTIVE: To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. METHODS: Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 +/- 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). RESULTS: Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). CONCLUSIONS: Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.","Aged;Aging/*pathology;Blood Pressure/physiology;Brachial Artery/pathology/physiopathology;Brain/*pathology;Cognition/physiology;Cohort Studies;Endothelium/*pathology;Female;Hemodynamics;Humans;Magnetic Resonance Imaging;Male;Manometry/methods;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Residence Characteristics;Retrospective Studies;Ultrasonography, Doppler, Pulsed;*Vascular Stiffness","Tsao, C. W.;Seshadri, S.;Beiser, A. S.;Westwood, A. J.;Decarli, C.;Au, R.;Himali, J. J.;Hamburg, N. M.;Vita, J. A.;Levy, D.;Larson, M. G.;Benjamin, E. J.;Wolf, P. A.;Vasan, R. S.;Mitchell, G. F.",2013,Sep 10,10.1212/WNL.0b013e3182a43e1c,0,
748,Association of arterial stiffness with progression of subclinical brain and cognitive disease,"OBJECTIVE: We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing. METHODS: Framingham Offspring Cohort participants (n = 1,223, 61 +/- 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 +/- 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (DeltaTrails B-A), and Similarities tests. RESULTS: Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and DeltaTrails B-A association: SD unit change in outcome variable per SD change in tonometry variable [beta] +/- SE = 0.10 +/- 0.04, p = 0.019; CPP and DeltaSimilarities association: -0.08 +/- 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([beta +/- SE] 0.07 +/- 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume. CONCLUSIONS: In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.",,"Tsao, C. W.;Himali, J. J.;Beiser, A. S.;Larson, M. G.;DeCarli, C.;Vasan, R. S.;Mitchell, G. F.;Seshadri, S.",2016,Feb 16,10.1212/wnl.0000000000002368,0,
749,Sydney Memory and Ageing Study: an epidemiological cohort study of brain ageing and dementia,"Non-demented community-dwelling older adults aged 70-90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%. Risk factors for MCI include APOE epsilon4 allele carrier status, high homocysteine, heart disease, poor odour identification, low visual acuity and low mental activity, but notable age and sex differences were observed. Neuropsychiatric symptoms were rare; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were associated with cognitive impairment. Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline. Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar, as were risk factors for progression to dementia.","Aged;Aged, 80 and over;Aging/*pathology/*physiology;Brain/pathology/*physiopathology;Cohort Studies;Dementia/epidemiology/physiopathology;Female;Humans;Male;Memory/*physiology;Mild Cognitive Impairment/*epidemiology/*physiopathology;New South Wales/epidemiology","Tsang, R. S.;Sachdev, P. S.;Reppermund, S.;Kochan, N. A.;Kang, K.;Crawford, J.;Wen, W.;Draper, B.;Trollor, J. N.;Slavin, M. J.;Mather, K. A.;Assareh, A.;Seeher, K. M.;Brodaty, H.",2013,Dec,10.3109/09540261.2013.860890,0,
750,Optimizing regions-of-interest composites for capturing treatment effects on brain amyloid in clinical trials,"BACKGROUND: Pittsburgh Compound B (PiB) positron emission tomography (PET) neuroimaging is a powerful research tool to characterize amyloid evolution in the brain. Quantification of amyloid load critically depends on (i) the choice of a reference region (RR) and (ii) on the selection of regions of interest (ROIs) to derive the standard uptake value ratios (SUVRs). OBJECTIVE: To evaluate the stability, i.e., negligible amyloid accumulation over time, of different RRs, and the performance of different PiB summary measures defined by selected ROIs and RRs for their sensitivity to detecting longitudinal change in amyloid burden. METHODS: To evaluate RRs, cross-sectional and longitudinal analyses of focal regional and composite measures of amyloid accumulation were carried out on the standardized PiB-PET regional data for cerebellar grey matter (CER), subcortical white matter (SWM), and pons (PON). RRs and candidate composite SUVR measures were further evaluated to select regions and develop novel composites, using standardized 2-year change from baseline. RESULTS: Longitudinal trajectories of PiB4-average of anterior cingulate (ACG), frontal cortex (FRC), parietal cortex, and precuneus-demonstrated marked variability and small change from baseline when normalized to CER, larger changes and less variability when normalized to SWM, which was further enhanced for the composite in PON-normalized settings. Novel composite PiB3, comprised of the average SUVRs of lateral temporal cortex, ACG, and FRC was created. CONCLUSION: PON and SWM appeared to be more stable RRs than the CER. PiB3 showed compelling sample size reduction and gains in power calculations for clinical trials over conventional PiB4 composite.","Aged;Aged, 80 and over;Amyloid/ metabolism;Brain/drug effects/metabolism/ radionuclide imaging;Cross-Sectional Studies;Female;Humans;Image Processing, Computer-Assisted/ methods;Longitudinal Studies;Male;Neuroimaging/ methods;Plaque, Amyloid/drug therapy/metabolism/ radionuclide imaging;Positron-Emission Tomography/ methods","Tryputsen, V.;DiBernardo, A.;Samtani, M.;Novak, G. P.;Narayan, V. A.;Raghavan, N.",2015,,10.3233/jad-131979,0,
751,"Adult mental deterioration, the main limiting factor in cerebral radiotherapy?","To specify the risks and characteristics of adult mental deterioration occurring after brain radiotherapy, we reviewed the literature since the late seventies. Selected series include a total of 978 patients who were given prophylactic or therapeutic cranial irradiation. Symptoms appear within a few months, and then steadily worsen. According to the severity of neuropsychologic symptoms, two clinical presentations may be individualized: minor deteriorations with memory loss or attention abnormalities and delayed",,"Trouette, R.;Caudry, M.;Maire, J. P.;Demeaux, H.",1993,1993,,0,
752,Motor and extramotor neurodegeneration in amyotrophic lateral sclerosis: a 3T high angular resolution diffusion imaging (HARDI) study,"In amyotrophic lateral sclerosis (ALS), diffusion weighted magnetic resonance imaging (DW-MRI) has produced mounting evidence of a widespread white matter (WM) damage within motor and extramotor pathways. To provide novel information about the degenerative process in ALS, overcoming some of the limitations imposed by diffusion tensor imaging (DTI), we performed a high angular resolution diffusion imaging (HARDI) analysis of DW-MRI data. Generalized fractional anisotropy (GFA) was evaluated in 19 patients with ALS and 19 matched control subjects, and was correlated with clinical scores of disability, pyramidal impairment by upper motor neuron (UMN) score and frontal dysfunction by the Frontal Systems Behaviour (FrSBe) scale. Results demonstrated that ALS patients showed a significant decrease of GFA in the WM tracts underneath the left and right precentral gyri and the body of the corpus callosum (p < 0.05, corrected), where GFA was significantly related to UMN scores (p < 0.001, uncorrected); and in the left superior longitudinal fasciculus (p < 0.05, corrected), where GFA was significantly related to FrSBe scale scores (p < 0.01, uncorrected). In conclusion, this study revealed a pattern of motor and extramotor frontal diffusivity abnormalities (probably related to behavioural and cognitive dysfunctions) showing a spatial distribution similar to what was previously described in ALS - frontotemporal dementia continuum.","Aged;Amyotrophic Lateral Sclerosis/ diagnosis/epidemiology/metabolism;Anisotropy;Cohort Studies;Diffusion Tensor Imaging/ methods;Female;Frontotemporal Dementia/ diagnosis/epidemiology/metabolism;Humans;Male;Middle Aged;Motor Skills Disorders/ diagnosis/epidemiology/metabolism;Nerve Fibers, Myelinated/metabolism/ pathology","Trojsi, F.;Corbo, D.;Caiazzo, G.;Piccirillo, G.;Monsurro, M. R.;Cirillo, S.;Esposito, F.;Tedeschi, G.",2013,Dec,10.3109/21678421.2013.785569,0,
753,A kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A 2-year neuropsychological follow-up,"We report a 2-year prospective neuropsychological study of five asymptomatic subjects with magnetic resonance imaging (MRI) abnormalities from an Italian kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). These subjects completed tests for attention capacities, processing speed, abstract thinking, short-term memory, learning and constructional praxis. Seven normal subjects matched for age and education, belonging to the same pedigree and not having MRI hyperintensities were examined as controls. The results did not show significant differences between asymptomatic subjects and normal controls. Cognitive performance of asymptomatic subjects did not deteriorate during a 2-year follow-up. Our findings suggest that, at this stage of the disease process, the presence of diffuse leukoencephalopathy does not imply subtle cognitive defects.","Adult;Aged;Cerebral Arterial Diseases/diagnosis/ physiopathology;Cognition;Dementia, Multi-Infarct/diagnosis/ physiopathology;Female;Follow-Up Studies;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/ physiopathology;Magnetic Resonance Imaging;Male;Memory;Middle Aged;Neuropsychological Tests;Pedigree;Prospective Studies","Trojano, L.;Ragno, M.;Manca, A.;Caruso, G.",1998,Apr,,0,
754,Delayed visual P3 in unilateral thalamic stroke,"The P3 potential is accepted as a neurophysiological correlate of memory and attention. Delayed latencies were reported in different forms of dementias. Although the generator sites are still under debate, the thalamus may play a crucial role. The aim of this study was to investigate the influence of an unilateral thalamic ischaemic infarction on P3 generation. The event-related P3 component of six patients (2 male, four female; mean age 47 years, range 22-63 years) with unilateral thalamic ischaemic infarction was studied and compared to age-matched controls (five male, nine female; mean age 45.8 years; range 22-69 years). All patients underwent full clinical examination, CCT, and MRI scan. P3 potentials were recorded with a visual three stimulus discrimination paradigm. The mean P3 latency of the patient group to the target stimulus was delayed (469.7 ms, SD = 36.8) compared with the controls (378.8 ms, SD = 51.5; P < 0. 05). The mean P3 latency to the unexpected stimulus was delayed in patients with thalamic infarction compared with controls [477 ms (SD = 46.6) vs. 381.2 ms (SD = 48.5); P < 0.001). Delayed P3 components of the event-related potential (ERP) were recorded in six patients with unilateral thalamic infarction, suggesting an important role of the thalamus in the generation of the P3 potential.","Adult;Aged;Attention/physiology;Electroencephalography;Event-Related Potentials, P300/*physiology;Evoked Potentials, Visual/*physiology;Female;Functional Laterality/physiology;Humans;Infarction, Posterior Cerebral Artery/pathology/*physiopathology;Male;Middle Aged;Reaction Time/physiology;Thalamus/pathology/*physiopathology","Trinka, E.;Unterrainer, J.;Staffen, W.;Loscher, N. W.;Ladurner, G.",2000,Sep,,0,
755,An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura), psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.",Cerebral autosomal-dominant arteriopathy with subcortical infarcts and;leukoencephalopathy (CADASIL);dementia;magnetic resonance imaging (MRI);migraine;occipital lobe;seizures,"Trikamji, B.;Thomas, M.;Hathout, G.;Mishra, S.",2016,Apr-Jun,10.4103/0972-2327.173403,0,
756,"CT in dementia, epilepsy and non-specific neurological symptoms without signs: Is there a place for radionuclide scanning?","8580 computed tomography (CT) examinations have been performed at the Royal Melbourne Hospital. The indications for examination fell into seven main groups: (I) clinical suspicion of intracranial focal lesion, based on focal symptoms and signs; (II) head trauma; (III) follow-up scans after craniotomy; (IV) cerebrovascular accident; (V) dementia; (VI) epilepsy; (VII) non-specific symptoms without neurological signs (headache, blackouts and vertigo). It is accepted that CT should be the initial examination for patients in the first three categories. The role of CT in the investigation of cerebrovascular disease lies principally in distinguishing between haemorrhage and infarction when they enter into the differential diagnosis. The justification for performing CT as the initial examination upon patients in the latter three categories is less certain. Therefore, the results of CT in the latter three categories were examined over a 12-month period, during which a total of 2492 examinations were performed.",central nervous system;cerebrovascular accident;computer analysis;computer assisted tomography;dementia;diagnosis;epilepsy;etiology;head injury;major clinical study,"Tress, B. M.;Hare, W. S. C.",1979,,,0,
757,The distribution of cerebrovascular amyloid in Alzheimer's disease varies with ApoE genotype,"We performed a comparative study to assess cerebral amyloid angiopathy and ApoE genotype in cases of Alzheimer's disease (AD). Ten ApoE 3,3 and ten ApoE 4,4 AD brains, as well as ten normal control brains, were selected after matching for age, sex, and duration of disease. Sections of middle frontal and inferior parietal cortex including white matter sections were stained with an antibody against amyloid beta (Abeta), and extensive analysis of arteriolar Abeta deposition was performed using digital image analysis. Quantification of the staining revealed a larger cross-section of arteriolar walls occupied by Abeta in ApoE 4,4 and ApoE 3,3 AD subjects compared to controls. Our results show Abeta deposition in gray matter and white matter arterioles was predominantly found in ApoE 4,4 brains and, overall, Abeta deposition was greatest in these cases. This observation implies that there is greater vascular amyloid deposition (particularly in the white matter arterioles) in ApoE 4,4 AD individuals compared to ApoE 3,3 AD. These observations may give insight into the etiology behind the increased risk for AD associated with the ApoE-epsilon4 allele and the pathogenesis of vascular Abeta deposition.","Aged;Aged, 80 and over;Alzheimer Disease/genetics/ metabolism/pathology;Amyloid beta-Peptides/ blood;Analysis of Variance;Apolipoproteins E/ genetics;Blood Vessels/ metabolism;Case-Control Studies;Cerebrovascular Disorders/genetics/pathology;Female;Humans;Male;Postmortem Changes","Trembath, D.;Ervin, J. F.;Broom, L.;Szymanski, M.;Welsh-Bohmer, K.;Pieper, C.;Hulette, C. M.",2007,Jan,10.1007/s00401-006-0162-9,0,
758,Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke,"Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10-6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p 2.2 × 10-8; rs941898 [EVL], p 4.0 × 10-8; rs962888 [C1QL1], p 1.1 × 10-8; rs9515201 [COL4A2], p 6.9 × 10-9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.",adult;aged;ahcyl2 gene;article;Australia;Belgium;brain size;c1ql1 gene;cerebrovascular accident;col4a2 gene;community living;disease course;efemp1 gene;evl gene;female;gene;gene locus;genetic association;genetic susceptibility;haao gene;human;human genome;imaging software;independent variable;Italy;major clinical study;male;middle aged;nbeal1 gene;neurl gene;neuroimaging;nuclear magnetic resonance imaging;pdcd11 gene;pmf1 bglap gene;priority journal;sh3pxd2a gene;single nucleotide polymorphism;stroke patient;trim65 gene;United Kingdom;United States;white matter,"Traylor, M.;Zhang, C. R.;Adib-Samii, P.;Devan, W. J.;Parsons, O. E.;Lanfranconi, S.;Gregory, S.;Cloonan, L.;Falcone, G. J.;Radmanesh, F.;Fitzpatrick, K.;Kanakis, A.;Barrick, T. R.;Moynihan, B.;Lewis, C. M.;Boncoraglio, G. B.;Lemmens, R.;Thijs, V.;Sudlow, C.;Wardlaw, J.;Rothwell, P. M.;Meschia, J. F.;Worrall, B. B.;Levi, C.;Bevan, S.;Furie, K. L.;Dichgans, M.;Rosand, J.;Markus, H. S.;Rost, N.",2016,,,0,
759,Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke,"BACKGROUND AND PURPOSE—: White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis. METHODS—: We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging–confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups. RESULTS—: The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI]]=1.14 [1.06–1.22]; P=0.0003), in patients both with and without WMH (WMH: OR [95% CI]=1.15 [1.05–1.26]; P=0.003 and no WMH: OR [95% CI]=1.11 [1.02–1.21]; P=0.019). Conversely, the risk score was not associated with cardioembolic stroke (OR [95% CI]=1.03 [0.97–1.09]; P=0.63) or large vessel stroke (OR [95% CI]=0.99 [0.93,1.04]; P=0.39). However, none of the WMH-associated single nucleotide polymorphisms passed Bonferroni-corrected significance for association with lacunar stroke. CONCLUSIONS—: Genetic variants that influence WMH are associated with an increased risk of lacunar stroke but not cardioembolic or large vessel stroke. Some genetic susceptibility factors seem to be shared across different radiological manifestations of small vessel disease.Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.",,"Traylor, M.;Rutten-Jacobs, L. C. A.;Thijs, V.;Holliday, E. G.;Levi, C.;Bevan, S.;Malik, R.;Boncoraglio, G.;Sudlow, C.;Rothwell, P. M.;Dichgans, M.;Markus, H. S.",2016,,,0,
760,In vivo PET study of cerebral (11)C methyltetrahydroaminoacridine distribution and kinetics in healthy human subjects,"It is unclear whether the palliative effects of tetrahydroaminoacridine (THA) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzheimer's disease (AD) are the result of its inhibitory activity on acetylcholinesterase or on other complex sites of action. In order to investigate the cerebral distribution and kinetics of THA in the human brain in vivo, we performed positron emission tomography (PET) imaging with [(11)C]N-methyl-tetrahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [(11)C]MTHA crossed the blood-brain barrier and reached its maximum uptake between 10 and 40 minutes, depending on the brain regions. Uptake was higher in the grey matter structures, and lower in the white matter. After this peak, the radioactivity remained quasi-constant until 60 minutes in all regions with a half-life varying from 2.44 hours in the thalamus to 3.42 hours in the cerebral cortex. The ratios of regional to whole cerebral cortex brain radioactivity calculated between 50 and 70 minutes after the tracer injection were 1.14 ± 0.04, 1.07 ± 0.03 and 1.06 ± 0.04 in the putamen, cerebellum and thalamus, respectively. Overall, these results show that: (1) [(11)C]MTHA crosses the blood-brain barrier easily and is highly concentrated in the brain; (2) the regional brain distribution of [(11)C]MTHA does not parallel that of in vivo acetylcholinesterase (AChE) concentrations; and (3) the cerebral kinetics of [(11)C]MTHA are consistent with known plasmatic pharmacokinetics of THA in AD patients. We conclude that PET imaging with [(11)C]MTHA is a useful method for assessing the cerebral distribution and kinetics of THA in vivo.",,"Traykov, L.;Tavitian, B.;Jobert, A.;Boller, F.;Forette, F.;Crouzel, C.;Di Giamberardino, L.;Pappata, S.",1999,1999,,0,
761,Does the Clock Drawing Test have focal neuroanatomical correlates?,"The Clock Drawing Test (CDT) is widely used in clinical neuropsychological practice. The CDT has been used traditionally as a ""parietal lobe"" test (e.g., Kaplan, 1988), but most empirical work has focused on its sensitivity and specificity for detecting and differentiating subtypes of dementia. There are surprisingly few studies of its neuroanatomical correlates. The authors investigated the neuroanatomical correlates of the CDT, using 133 patients whose lesions provided effective coverage of most of both hemispheric convexities and underlying white matter. On the CDT, 30 subjects were impaired and 87 were unimpaired (16 were ""borderline""). Impairments on the CDT were associated with damage to right parietal cortices (supramarginal gyrus) and left inferior frontal-parietal opercular cortices. Visuospatial errors were predominant in patients with right hemisphere damage, whereas time setting errors were predominant in patients with left hemisphere lesions. These findings provide new empirical evidence regarding the neuroanatomical correlates of the CDT, and together with previous work, support the use of this quick and easily administered test not only as a screening measure but also as a good index of focal brain dysfunction.","Adult;Aged;Analysis of Variance;Brain/pathology/*physiopathology;Brain Damage, Chronic/diagnosis/*physiopathology;Female;Functional Laterality;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Neuropsychological Tests;Parietal Lobe/pathology/physiopathology;Psychometrics;Psychomotor Performance/*physiology;Spatial Behavior/physiology;Time Perception/*physiology","Tranel, D.;Rudrauf, D.;Vianna, E. P.;Damasio, H.",2008,Sep,10.1037/0894-4105.22.5.553,0,
762,Candidate-gene analysis of white matter hyperintensities on neuroimaging,"Background: White matter hyperintensities (WMH) are a common radiographic finding and may be a useful endophenotype for small vessel diseases. Given high heritability of WMH, we hypothesised that certain genotypes may predispose individuals to these lesions and consequently, to an increased risk of stroke, dementia and death. We performed a meta-analysis of studies investigating candidate genes and WMH to elucidate the genetic susceptibility to WMH and tested associated variants in a new independent WMH cohort. We assessed a causal relationship of WMH to methylene tetrahydrofolate reductase (MTHFR). Methods: Database searches through March 2014 were undertaken and studies investigating candidate genes in WMH were assessed. Associated variants were tested in a new independent ischaemic cohort of 1202 WMH patients. Mendelian randomization was undertaken to assess a causal relationship between WMH and MTHFR. Results: We identified 43 case-control studies interrogating eight polymorphisms in seven genes covering 6,314 WMH cases and 15,461 controls. Fixedeffects meta-analysis found that the C-allele containing genotypes of the aldosterone synthase CYP11B2 T(-344)C gene polymorphism were associated with a decreased risk of WMH (OR=0.61; 95% CI, 0.44 to 0.84; p=0.003). Using mendelian randomisation the association among MTHFR C677T, homocysteine levels and WMH, approached, but did not reach, significance (expected OR=1.75; 95% CI, 0.90-3.41; observed OR=1.68; 95% CI, 0.97-2.94). Neither CYP11B2 T(-344)C nor MTHFR C677T were significantly associated when tested in a new independent cohort of 1202 patients with WMH. Conclusions: There is a genetic basis to WMH but anonymous genome wide and exome studies are more likely to provide novel loci of interest.","5,10 methylenetetrahydrofolate reductase (FADH2);aldosterone synthase;homocysteine;allele;article;brain ischemia;case control study;cohort analysis;computer assisted tomography;CYP11B2 gene;genetic analysis;genetic polymorphism;genetic susceptibility;genetic variability;genotype;human;MTHFR gene;neuroimaging;nuclear magnetic resonance imaging;priority journal;randomization;risk reduction;white matter hyperintensity;white matter lesion","Tran, T.;Cotlarciuc, I.;Yadav, S.;Hasan, N.;Bentley, P.;Levi, C.;Worrall, B. B.;Meschia, J. F.;Rost, N.;Sharma, P.",2016,,,0,
763,Effects of zidovudine in 30 patients with mild to end-stage AIDS dementia complex,"OBJECTIVE: Zidovudine (ZDV) is an inhibitor of HIV replication that may have a beneficial effect on patients with AIDS dementia complex (ADC). However, little is known about the association between long-term ZDV treatment and severity of ADC, ZDV dose or clinical and laboratory response to therapy. DESIGN: An open study on ZDV administration in 30 consecutive patients with ADC. SETTING: An infectious diseases hospital. PATIENTS: Thirty consecutive patients followed-up for 12 months. INTERVENTIONS: Three oral ZDV doses were used: 1000 mg (nine patients), 750 mg (eight patients) and 500 mg (13 patients) per day, depending on haematological status. MAIN OUTCOME MEASURES: Clinical and neurological examinations, neuropsychological evaluations, high-field brain magnetic resonance imaging (MRI) and 99mTc-HM-PAO single photon emission computerized tomography (SPECT). RESULTS: A favourable clinical response, defined as reversal to a less severe ADC stage (Price and Brew's criteria), was observed after 1, 3, 6, 9 and 12 months in 15, 22, 25, 19 and 14 patients, respectively. Neither severity of ADC at entry nor ZDV dose correlated with response to treatment. Seven patients died during the 12-month follow-up. The only factor associated with longer survival was ADC severity at entry (12-month survival, 0.94 and 0.53, in patients in stages 1 or 2 and in stages 3 or 4, respectively; P < 0.01). After 6-12 months of ZDV treatment six patients who initially responded to therapy showed a relapse in initial ADC stage, and two patients a less severe neurological deterioration. Neuropsychological evaluations showed significant improvement in the Wisconsin Card-Sorting test (P = 0.006 for categories, P = 0.029 for perseverative errors), which is particularly sensitive to cognitive and frontal-lobe type functions. Brain MRI revealed a reduction of the extent of white matter lesions in six out of 13 patients, who also showed clinical improvement. SPECT scanning revealed a reduction in the extent of uptake defects concomitant with clinical response in nine out of 14 patients. CONCLUSIONS: ZDV is effective in most patients with mild to end-stage ADC, although the benefit is sometimes only transient; several relapses and deaths occurred after the sixth month of treatment.","AIDS Dementia Complex/diagnosis/ drug therapy/psychology;Adult;Dose-Response Relationship, Drug;Drug Evaluation;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Time Factors;Tomography, Emission-Computed, Single-Photon;Zidovudine/administration & dosage/ therapeutic use","Tozzi, V.;Narciso, P.;Galgani, S.;Sette, P.;Balestra, P.;Gerace, C.;Pau, F. M.;Pigorini, F.;Volpini, V.;Camporiondo, M. P.;et al.",1993,May,,0,
764,Quantitative magnetisation transfer imaging in glioma: preliminary results,"Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule-bound protons; these include the bound proton fraction and the relaxation times of free and bound proton pools. It has been used in multiple sclerosis and Alzheimer's disease, and has shown changes in some of the parameters, particularly the bound proton fraction. The purpose of this pilot study was to assess whether qMTI could distinguish between gliomas and normal brain tissue, and provide proof of principle for its use in tumour characterisation. Eight subjects [three men, five women; mean age, 44 years; range, 27-66 years; seven World Health Organization (WHO) Grade II, one Grade III] with biopsy-proven glioma were imaged with a structural MRI protocol that included three-dimensional qMTI. qMTI parameters were extracted from regions of interest selected from different tumour components visible on conventional MR sequences, normal-appearing peritumoral tissue and distant normal-appearing white matter. All patients gave informed consent and the study was approved by the Local Research Ethics Committee. Almost all of the qMTI parameters detected abnormalities in both glioma and the peritumoral region relative to the distant white matter. In particular, the bound proton fraction was reduced significantly from 6.0 percentage units (pu) [standard deviation (SD), 0.5 pu] in normal-appearing white matter to 1.7 pu (SD = 0.5 pu) in solid tumour and 2.2 pu (SD = 0.5 pu) in peritumoral areas. This work shows that qMTI reveals abnormalities, not only in glioma, but also in the apparently normal tissue surrounding the conventionally defined tumour. Thus, qMTI shows promise for tumour characterisation and for studying tumour boundaries. These preliminary data justify larger studies in a range of different tumour types and grades.",Adult;Aged;Diagnostic Imaging/ methods;Female;Glioma/ pathology;Humans;Magnetics/ methods;Male;Middle Aged,"Tozer, D. J.;Rees, J. H.;Benton, C. E.;Waldman, A. D.;Jager, H. R.;Tofts, P. S.",2011,Jun,10.1002/nbm.1614,0,
765,White matter tract damage in the behavioral variant of frontotemporal and corticobasal dementia syndromes,"The phenotypes of the behavioral variant of frontotemporal dementia and the corticobasal syndrome present considerable clinical and anatomical overlap. The respective patterns of white matter damage in these syndromes have not been directly contrasted. Beyond cortical involvement, damage to white matter pathways may critically contribute to both common and specific symptoms in both conditions. Here we assessed patients with the behavioral variant of frontotemporal dementia and corticobasal syndrome with whole-brain diffusion tensor imaging to identify the white matter networks underlying these pathologies. Twenty patients with the behavioral variant of frontotemporal dementia, 19 with corticobasal syndrome, and 15 healthy controls were enrolled in the study. Differences in tract integrity between (i) patients and controls, and (ii) patients with the corticobasal syndrome and the behavioral variant of frontotemporal dementia were assessed with whole brain tract-based spatial statistics and analyses of regions of interest. Behavioral variant of frontotemporal dementia and the corticobasal syndrome shared a pattern of bilaterally decreased white matter integrity in the anterior commissure, genu and body of the corpus callosum, corona radiata and in the long intrahemispheric association pathways. Patients with the behavioral variant of frontotemporal dementia showed greater damage to the uncinate fasciculus, genu of corpus callosum and forceps minor. In contrast, corticobasal syndrome patients had greater damage to the midbody of the corpus callosum and perirolandic corona radiata. Whereas several compact white matter pathways were damaged in both the behavioral variant of frontotemporal dementia and corticobasal syndrome, the distribution and degree of white matter damage differed between them. These findings concur with the distinctive clinical manifestations of these conditions and may improve the in vivo neuroanatomical and diagnostic characterization of these disorders.",Aged;Analysis of Variance;Brain/pathology/physiopathology;Brain Mapping;Cerebral Cortex/pathology/ physiopathology;Dementia/ physiopathology;Diffusion Tensor Imaging/methods;Female;Frontotemporal Dementia/ physiopathology;Humans;Male;Middle Aged;Syndrome;White Matter/pathology/ physiopathology,"Tovar-Moll, F.;de Oliveira-Souza, R.;Bramati, I. E.;Zahn, R.;Cavanagh, A.;Tierney, M.;Moll, J.;Grafman, J.",2014,,10.1371/journal.pone.0102656,0,
766,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been recently reported as a cause of stroke. It is characterized, in the absence of hypertension, by recurrent subcortical ischaemic strokes, starting in early or midadulthood and leading in some patients to dementia. Magnetic resonance imaging and pathological examination show numerous small subcortical infarcts and a diffuse leukoencephalopathy underlaid by a non-arteriosclerotic, non-amyloid angiopathy. We performed genetic linkage analysis in two unrelated families and assigned the disease locus to chromosome 19q12. Multilocus analysis with the location scores method established the best estimate for the location of the affected gene within a 14 centimorgan interval bracketed by D19S221 and D19S222 loci.",,"Tournier-Lasserve, E.;Joutel, A.;Melki, J.;Weissenbach, J.;Lathrop, G. M.;Chabriat, H.;Mas, J. L.;Cabanis, E. A.;Baudrimont, M.;Maciazek, J.;Bach, M. A.;Bousser, M. G.",1993,1993,,0,
767,Autosomal dominant syndrome with strokelike episodes and leukoencephalopathy,"Background and Purpose: We conducted a prospective survey of a family presenting a new syndrome characterized mainly by recurrent strokelike episodes and neuroimaging evidence of leukoencephalopathy. Summary of Report: Forty-five members of a single family were studied clinically and with magnetic resonance imaging. Nine had strokelike episodes, including transient ischemic attacks, and minor or major strokes starting between the fourth and sixth decades, with neuroimaging evidence of small, deep infarcts and a widespread white matter disorder. Other symptoms included migraine (three), dementia (two), epilepsy (one), and hearing loss (one). In some patients, we found various immunologic anomalies and muscular lipidosis without ragged-red fibers. Eight other family members were clinically normal, but had identical neuroimaging signs of leukoencephalopathy. No abnormality was detected in the 28 other members of the family examined. Extensive investigations failed to reveal any known cause of cerebral ischemia. Conclusions: There appears to be a new syndrome in this family that is characterized by recurrent subcortical strokelike episodes, leukoencephalopathy, immunologic anomalies, muscular lipidosis, and an autosomal dominant pattern of transmission.",,"Tournier-Lasserve, E.;Iba-Zizen, M. T.;Romero, N.;Bousser, M. G.",1991,1991,,0,
768,Meningovascular neurosyphilis as the cause of ischemic cerebrovascular disease in a young man,"Authors report a case of a 35-year-old male with right-sided mild paresis, incontinence, dysexecutive syndrome, short-term memory loss and behavioral changes. Bilateral cerebral infarcts in the region of the caudate nuclei and the adjacent white matter were proved by brain MRI and multiple stenoses of the branches of Willis-circle were confirmed by MR angiography. Elevated protein level and pleocytosis were found in the cerebrospinal fluid with intrathecal IgG synthesis. Serum rapid plasma reagin, Treponema pallidum Particle Agglutination test, Treponema pallidum ELISA, liquor Venereal Disease Research Laboratory tests were positive. Meningovascular neurosyphilis was diagnosed. 24M U/day intravenous penicillin-G treatment was given for 14 days. The patient has vascular dementia due to the bilateral strategic infarcts disconnecting the prefrontal circuits; his symptoms are similar to general paresis. Laboratory and radiologic improvement was observed. Still, the patient have severe residual cognitive decline.",immunoglobulin G;penicillin G;adult;article;brain circulus arteriosus;brain ischemia;case report;cerebrospinal fluid;enzyme linked immunosorbent assay;human;immunoglobulin production;laboratory test;magnetic resonance angiography;male;multiinfarct dementia;neuroimaging;neurosyphilis;pleocytosis;prefrontal cortex;treatment duration;Treponema pallidum;Treponema pallidum hemagglutination test;white matter,"Tóth, V.;Hornyák, C.;Kovács, T.;Tóth, B.;Várallyay, G.;Ostorházi, E.;Köles, J.;Bereczki, D.;Marschalkó, M.;Kárpáti, S.",2011,,,0,
769,The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment,"INTRODUCTION: It is unclear whether white matter hyperintensities (WMHs), magnetic resonance imaging markers of small-vessel cerebrovascular disease, promote neurodegeneration and associated clinical decline in Alzheimer's disease (AD), or simply co-occur with recognized pathogenic processes. METHODS: In 169 patients with mild cognitive impairment, followed for 3 years, we examined the association of (1) baseline regional WMH and cerebral spinal fluid-derived t-tau (total tau) with entorhinal cortex atrophy rates, as a marker of AD-related neurodegeneration, and conversion to AD; and (2) baseline regional WMH with change in t-tau level. RESULTS: In participants with low baseline t-tau, higher regional WMH volumes were associated with faster entorhinal cortex atrophy. Higher parietal WMH volume predicted conversion to AD in those with high t-tau. Higher parietal and occipital WMH volumes predicted increasing t-tau. DISCUSSION: WMHs affect AD clinical and pathologic processes both directly and interacting with tau.",,"Tosto, G.;Zimmerman, M. E.;Hamilton, J. L.;Carmichael, O. T.;Brickman, A. M.",2015,Dec,10.1016/j.jalz.2015.05.014,0,
770,Predicting aggressive decline in mild cognitive impairment: the importance of white matter hyperintensities,"IMPORTANCE: Although white matter hyperintensities (WMHs) are associated with the risk for Alzheimer disease, it is unknown whether they represent an independent source of impairment or interact with known markers of disease. OBJECTIVE: To examine the degree to which WMHs predict aggressive cognitive decline among individuals with mild cognitive impairment, either independently or by modifying the effects of entorhinal cortex volume (ECV), a marker of Alzheimer disease-related neurodegeneration. DESIGN, SETTING, AND PARTICIPANTS: The Alzheimer's Disease Neuroimaging Initiative is a longitudinal study with 6-month follow-up visits. Three hundred thirty-two participants (mean [SD] age, 74.6 [7.4] years; 118 women) of a total of 374 participants diagnosed as having mild cognitive impairment were included. Participants were excluded if they did not have longitudinal data, apolipoprotein E genotype data, or had evidence of supratentorial infarct. MAIN OUTCOMES AND MEASURES: A decline in Mini-Mental State Examination score of 3 points over 6 months or 6 points over 1 year between consecutive visits was defined as aggressive decline. White matter hyperintensity volume and ECV were entered as predictors in Cox proportional hazards models and Wilcoxon-Breslow tests to examine their impact on this outcome, adjusting for sex, age, education, and apolipoprotein E status. RESULTS: Greater WMH volume at baseline, apolipoprotein E epsilon4 status, and smaller ECV at baseline were associated with an increased risk for aggressive decline (hazard ratio [HR], 1.23; 95% CI, 1.05-1.43; P = .01 for WMH volume; HR, 1.49; 95% CI, 1.09-2.05; P = .04 for apolipoprotein E epsilon4 status; HR, 0.66; 95% CI, 0.55-0.79; P < .001 for ECV). White matter hyperintensity volume modified the effect of ECV on aggressive decline risk: individuals with high ECV and low WMH were at particularly low likelihood of decline (chi2 = 15, P = .001). Participants with Mini-Mental State Examination scores that declined by 3 or more points over 6 months or 6 or more points over 12 months were more likely to have converted to Alzheimer disease by the end of the follow-up period (chi2 = 82, P < .001). CONCLUSIONS AND RELEVANCE: White matter hyperintensity burden and ECV predict rapid cognitive decline among individuals with mild cognitive impairment both additively and multiplicatively.","Aged;Aged, 80 and over;Atrophy/pathology;Cognitive Dysfunction/diagnosis/ pathology/ physiopathology;Disease Progression;Entorhinal Cortex/pathology;Female;Humans;Leukoencephalopathies/diagnosis/ pathology/ physiopathology;Magnetic Resonance Imaging;Male;Predictive Value of Tests;Prognosis;Prospective Studies;Risk Factors","Tosto, G.;Zimmerman, M. E.;Carmichael, O. T.;Brickman, A. M.;Alzheimer's Disease Neuroimaging, Initiative",2014,Jul 1,,0,
771,Predicting aggressive decline in mild cognitive impairment: the importance of white matter hyperintensities,"IMPORTANCE: Although white matter hyperintensities (WMHs) are associated with the risk for Alzheimer disease, it is unknown whether they represent an independent source of impairment or interact with known markers of disease. OBJECTIVE: To examine the degree to which WMHs predict aggressive cognitive decline among individuals with mild cognitive impairment, either independently or by modifying the effects of entorhinal cortex volume (ECV), a marker of Alzheimer disease-related neurodegeneration. DESIGN, SETTING, AND PARTICIPANTS: The Alzheimer's Disease Neuroimaging Initiative is a longitudinal study with 6-month follow-up visits. Three hundred thirty-two participants (mean [SD] age, 74.6 [7.4] years; 118 women) of a total of 374 participants diagnosed as having mild cognitive impairment were included. Participants were excluded if they did not have longitudinal data, apolipoprotein E genotype data, or had evidence of supratentorial infarct. MAIN OUTCOMES AND MEASURES: A decline in Mini-Mental State Examination score of 3 points over 6 months or 6 points over 1 year between consecutive visits was defined as aggressive decline. White matter hyperintensity volume and ECV were entered as predictors in Cox proportional hazards models and Wilcoxon-Breslow tests to examine their impact on this outcome, adjusting for sex, age, education, and apolipoprotein E status. RESULTS: Greater WMH volume at baseline, apolipoprotein E ?4 status, and smaller ECV at baseline were associated with an increased risk for aggressive decline (hazard ratio [HR], 1.23; 95% CI, 1.05-1.43; P?=?.01 for WMH volume; HR, 1.49; 95% CI, 1.09-2.05; P?=?.04 for apolipoprotein E ?4 status; HR, 0.66; 95% CI, 0.55-0.79; P?<?.001 for ECV). White matter hyperintensity volume modified the effect of ECV on aggressive decline risk: individuals with high ECV and low WMH were at particularly low likelihood of decline (?2?=?15, P?=?.001). Participants with Mini-Mental State Examination scores that declined by 3 or more points over 6 months or 6 or more points over 12 months were more likely to have converted to Alzheimer disease by the end of the follow-up period (?2?=?82, P?<?.001). CONCLUSIONS AND RELEVANCE: White matter hyperintensity burden and ECV predict rapid cognitive decline among individuals with mild cognitive impairment both additively and multiplicatively.","Atrophy [pathology];Disease Progression;Entorhinal Cortex [pathology];Leukoencephalopathies [diagnosis] [pathology] [physiopathology];Magnetic Resonance Imaging;Mild Cognitive Impairment [diagnosis] [pathology] [physiopathology];Predictive Value of Tests;Prognosis;Prospective Studies;Risk Factors;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Tosto, G.;Zimmerman, M. E.;Carmichael, O. T.;Brickman, A. M.",2014,,10.1001/jamaneurol.2014.667,0,
772,Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease,"BACKGROUND: Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI). METHODS: Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD. RESULTS: Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD. CONCLUSIONS: This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.",Aged;Alzheimer Disease/ psychology;Apathy;Atrophy/pathology;Behavior;Brain Mapping;Case-Control Studies;Female;Gray Matter/pathology;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/psychology;Neuropsychological Tests;Thalamus/ pathology;White Matter/pathology,"Torso, M.;Serra, L.;Giulietti, G.;Spano, B.;Tuzzi, E.;Koch, G.;Caltagirone, C.;Cercignani, M.;Bozzali, M.",2015,,10.1371/journal.pone.0124998,0,
773,Medial temporal lobe atrophy is underreported and may have important clinical correlates in medical inpatients,"BACKGROUND: The diagnostic workup in dementia includes brain imaging with reading focussed on signs of cerebrovascular and neurodegenerative disease. We hypothesised that these findings may be underreported in hospital patients, where imaging is often performed to rule out obvious pathology such as haemorrhage. In this study, we review cranial computed tomography (CT) in medical inpatients for white matter changes and atrophy. Our aim was to determine the clinical relevance of such findings and to what extent they were underreported. METHODS: Records from 200 inpatients aged over 60 years, who had been subjected to MMSE (mini-mental state examination) and CDT (clock-drawing test), were reviewed for cranial CT. Transverse and coronal slices were reassessed using visual rating scales regarding white matter changes (WMC), global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA). Findings were compared with the original radiology reports and cognitive test results. RESULTS: Cranial CT had been performed in 94 of 200(47 %) patients. Of these, 58(62 %) had abnormal WMC, 35(37 %) abnormal GCA and 34(36 %) abnormal MTA. All three findings had associations with cognitive test results. Abnormal MTA was associated with lower results on the overall score on MMSE and on orientation, memory and language items. All three measurements were underreported in the original radiology reports; none of the 34 patients with abnormal MTA had been reported originally. CONCLUSIONS: Signs of neurodegenerative disease, especially MTA, were highly underreported in cranial CT scans performed in medical inpatients. At the same time, MTA seemed to hold the most important clinical correlates. Our results suggest that MTA should be reported more regularly in this setting.","Aged;Aged, 80 and over;Atrophy/pathology/radiography;Dementia/ pathology/radiography;Female;Hospitalization;Humans;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies;Temporal Lobe/ pathology/radiography;Tomography, X-Ray Computed;White Matter/ pathology/radiography","Torisson, G.;van Westen, D.;Stavenow, L.;Minthon, L.;Londos, E.",2015,,10.1186/s12877-015-0066-4,0,
774,Vascular changes and brain plasticity: a new approach to neurodegenerative diseases,"The world's population is aging, which will result in an increasing prevalence of neurodegenerative diseases, such as dementia. Observations from functional brain imaging that older brains can be more active than their younger counterparts challenge stereotypical ideas of aging. In those aging successfully, brain activation is more anterior, less lateralized and more coordinated than in those at risk of, or suffering from, cognitive impairment. Several theories have been proposed to explain these findings. One of the most enticing is the scaffolding theory, which posits that the older brain is a plastic homeostatic organ, able to compensate for its deteriorating structure. However, with aging also come diffuse vascular changes and the resulting white matter damage. This decreases the compensatory capacity, and dementia can ensue. This and alternative hypotheses will be discussed, along with potential methodological problems of this genre of study and with their clinical implications.",,"Topiwala, A.;Ebmeier, K. P.",2012,,,0,
775,Resilience and MRI correlates of cognitive impairment in communitydwelling elders,"Background The contribution of education and intelligence to resilience against agerelated cognitive decline is not clear, particularly in the presence of 'normal for age' minor brain abnormalities. Method Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes. Results Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) 26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy. Conclusions Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.",,"Topiwala, A.;Allan, C. L.;Valkanova, V.;Zsoldos, E.;Filippini, N.;Sexton, C. E.;Mahmood, A.;Singh-Manoux, A.;Mackay, C. E.;Kivimäki, M.;Ebmeier, K. P.",2015,,,0,
776,Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: Longitudinal cohort study,"Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function. Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15). Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy). Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were ""alcohol dependent"" according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data. Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning. Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall. Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.",adult;adverse outcome;alcohol consumption;alcoholism;article;brain atrophy;brain cyst;brain function;cohort analysis;controlled study;diffusion tensor imaging;female;follow up;functional assessment;gray matter;human;image quality;longitudinal study;major clinical study;male;mental deterioration;mental performance;nuclear magnetic resonance imaging;outcome assessment;priority journal;questionnaire;risk assessment;risk factor;white matter,"Topiwala, A.;Allan, C. L.;Valkanova, V.;Zsoldos, E.;Filippini, N.;Sexton, C.;Mahmood, A.;Fooks, P.;Singh-Manoux, A.;Mackay, C. E.;Kivimäki, M.;Ebmeier, K. P.",2017,,10.1136/bmj.j2353,0,
777,Leigh syndrome in a 3-year-old boy with unusual brain MR imaging and pathologic findings,"We report unusual MR serial imaging and electron microscopy findings in a 3-year-old boy who had Leigh syndrome with cytochrome-c oxidase (cox) deficiency. The MR imaging findings included periventricular white matter involvement, posteroanterior progression, and extension through the corpus callosum and internal capsule; however, no basal ganglia or brain stem abnormality was found, which was suggestive of leukodystrophy. The most noteworthy findings were the cystic foci with contrast enhancement in the affected white matter.",,"Topçu, M.;Saatci, I.;Apak, R. A.;Söylemezoglu, F.;Akçören, Z.",2000,2000,,0,
778,A case of leukoencephalopathy with vanishing white matter,"A 6-year old Turkish boy with a recently defined entity: 'leukoencephalopathy with vanishing white matter' is described. He was born to consanguinoous parents. His psychomotor development was normal till he first presented with fever and generalized tonic-clonic seizures at the age of 2.5, followed by rapid motor and mental deterioration. Decerebrate posture and marked spasticity subsequently developed. The initial MRI examination showed diffuse involvement of white matter, including subcortical U-fibers, with signal intensity parallel to CSF on all sequences. The white matter appeared swollen. The ventricles were slightly enlarged and there was cavum septi pellucidi et vergae. The posterior crus of the internal capsule, external and extreme capsules were affected. Cerebellar hemispheres and vermis showed atrophy. The involvement pattern of brainstem was noteworthy in that pontine tegmentum and cruri cerebri were affected. Follow-up MRI obtained after three years did not show any interval change. Brain biopsy showed thinned cortex with relatively preserved cortical layering and neuronal structure. There was rarefaction of the white matter with cystic degeneration. Fibrillary gliosis and increased number of oligodendroglial cells were observed within the cerebral white matter.",article;body posture;brain biopsy;brain cortex;brain stem;brain ventricle;capsula interna;case report;cerebellum atrophy;cerebellum vermis;cerebrospinal fluid;consanguineous marriage;fever;gliosis;human;human tissue;leukoencephalopathy;male;mental deterioration;motor dysfunction;nuclear magnetic resonance imaging;oligodendroglia;pons angle;preschool child;priority journal;psychomotor development;septum pellucidum;spasticity;tegmentum;tonic clonic seizure;white matter,"Topçu, M.;Saatci, I.;Anil Apak, R.;Söylemezoglu, F.",2000,,,0,
779,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL): A rare cause of dementia,"The clinical course of a 60-year-old gentleman with a history of atypical migraine, recurrent encephalopathic episodes and progressive cognitive impairment is presented. He was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, a rare genetic disorder of the cerebral blood vessels caused by mutations in the Notch 3 gene on chromosome 19. The diagnosis was confirmed by MRI, skin biopsy and genetic testing. His cognitive function has progressively deteriorated and he continues to receive supportive care provision. The course and review of the condition are highlighted. Copyright © 2013 BMJ Publishing Group. All rights reserved.",acetazolamide;acetylsalicylic acid;aciclovir;autoantibody;desmopressin;diazepam;homocysteine;imipramine;latanoprost plus timolol;laxative;mirtazapine;Notch3 receptor;oxybutynin;promazine;ramipril;simvastatin;solifenacin;temazepam;tolterodine;adult;apraxia;article;attention disturbance;behavior disorder;Binswanger encephalopathy;blood analysis;brain ischemia;CADASIL;case report;cerebrospinal fluid examination;clinical feature;computer assisted tomography;confusion;daily life activity;dementia;depression;diagnostic test;differential diagnosis;disease association;disease course;disease severity;drug withdrawal;echocardiography;electrocardiogram;electroencephalogram;encephalitis;executive function;fall risk;family history;fever;follow up;gene;gene mutation;genetic screening;glaucoma;hemianopia;hospital admission;hospital discharge;human;hypertension;laboratory test;language disability;male;memory disorder;mental deterioration;migraine;multiple sclerosis;neurogenic bladder;neuroimaging;neurologic examination;nocturia;Notch 3 gene;nuclear magnetic resonance imaging;outpatient care;paresthesia;priority journal;psychiatry;psychometry;restlessness;skin biopsy;thrombophilia;treatment response;urine incontinence;virus encephalitis;visual disorder;weakness;wheelchair;white matter,"Toni-Uebari, T. K.",2013,,,0,
780,Effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease,"OBJECTIVE: To explore the effect of brain atrophy on the cognition in patients with subcortical ischemic vascular disease (SIVD). METHODS: A total of 116 SIVD patients were enrolled from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between September 2013 and December 2014. Lobar atrophy, leukoaraiosis (LA), lacunar infarcts (LI) and vascular risk factors were analyzed in the 116 SIVD patients who were divided into three groups according to the diagnostic criteria: non-cognitive impairment group (SIVD-NCI) , mild cognitive impairment group (SIVD-MCI) and dement group (SIVD-VaD). All patients underwent magnetic resonance imaging (MRI) with a 3.0-T system. The cognitive functions were evaluated by mini-metal state examination (MMSE), the Cambridge cognitive examination-Chinese version (CAMCOG-C), etc. A widely used visual atrophy rating method (0 to 3) was adopted to rate the severity of frontal, parietal and temporal lobe atrophy. The degree of LA and the numbers of LI in 4 brain regions (frontal, parieto-occipital, temporal, and basal ganglia) were evaluated meanwhile. RESULTS: Firstly, both the SIVD-MCI and SIVD-VaD groups showed significantly higher total scores of atrophy, higher frontal lobe atrophy scores, higher LA scores and larger LI numbers than SIVD-NCI (H=6.138, P=0.013; H=45.845, P=0.000; H=36.818, P=0.000; H=37.46, P=0.000). There were no significant differences in temporal lobe atrophy scores between SIVD-NCI group and SIVD-MCI group. Parietal lobe atrophy scores also showed no differences among the three groups. Secondly, as well as total numbers of LI, total scores of atrophy and LA were negatively correlated with SIVD cognition, especially frontal lobe atrophy scores, parieto-occipital LA scores and basal ganglia LI numbers had a remarkable negative correlation with MMSE scores, CAMCOG-C scores and partial subitems in CAMCOG-C scores (P<0.005). However temporal LI numbers was absence of correlation with MMSE scores, CAMCOG-C scores and subitems in CAMCOG-C scores (P>0.005). Thirdly, education (OR= 0.787, P=0.009), total scores of LA (OR= 1.201, P=0.036) and total numbers of LI (OR= 1.221, P=0.011) remained to be associated with cognition after controlling for sex, age, education, hypertension, diabetes, smoking. While, after adjusting atrophy scores, total scores of LA had no significant association with cognition. Atrophy scores, total numbers of LI and education still showed significant association with cognition, particularly frontal lobe atrophy scores (OR= 16.082, P=0.000), but not temporal and parietal lobe atrophy scores. CONCLUSIONS: Brain atrophy may be a new and independent predictive index of cognitive impairment in SIVD. Further, the effect of brain atrophy, the numbers of LI and degree of LA on cognitive decline is independent and decreases in turn.",Atrophy;Brain Ischemia;Cognition;Dementia;Humans;Leukoaraiosis;Magnetic Resonance Imaging;Mild Cognitive Impairment;Risk Factors,"Tong, X. X.;Wang, L.;Zhou, X.;Zhang, C.;Fang, L.;Zhou, Y. J.;Sun, Z. W.",2016,Jan 5,,0,
781,Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease,"BACKGROUND: White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. METHODS: This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). RESULTS: Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). CONCLUSIONS: The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD.",Alzheimer;Imaging mass spectrometry;Maldi;Streptozotocin;White matter degeneration,"Tong, M.;Leao, R.;Vimbela, G. V.;Yalcin, E. B.;Kay, J.;Krotow, A.;de la Monte, S. M.",2017,Jul,,0,
782,Targeting Alzheimer's Disease Neuro-Metabolic Dysfunction with a Small Molecule Nuclear Receptor Agonist (T3D-959) Reverses Disease Pathologies,"BACKGROUND: Alzheimer's disease (AD) could be regarded as a brain form of diabetes since insulin resistance and deficiency develop early and progress with severity of neurodegeneration. Preserving insulin's actions in the brain restores function and reduces neurodegeneration. T3D-959 is a dual nuclear receptor agonist currently in a Phase 2a trial in mild-to-moderate AD patients (ClinicalTrials.gov identifier NCT02560753). Herein, we show that T3D-959 improves motor function and reverses neurodegeneration in a sporadic model of AD. METHODS: Long Evans rats were administered intracerebral (i.c.) streptozotocin (STZ) or normal saline (control) and dosed orally with T3D-959 (1.0 mg/kg/day) or saline for 21 or 28 days. Rotarod tests evaluated motor function. Histopathology with image analysis was used to assess neurodegeneration. RESULTS: T3D-959 significantly improved motor performance, and preserved both cortical and normalized white matter structure in i.c STZ-treated rats. T3D-959 treatments were effective when dosed therapeutically, whether initiated 1 day or 7 days after i.c. STZ. CONCLUSION: T3D-959's targeting neuro-metabolic dysfunctions via agonism of PPAR delta and PPAR gamma nuclear receptors provides potential disease modification in AD.",Alzheimer;Cerebellum;Motor function;Neurodegeneration;PPAR agonist;Streptozotocin;T3d-959;Type 3 diabetes,"Tong, M.;Dominguez, C.;Didsbury, J.;de la Monte, S. M.",2016,Jun,10.4172/2161-0460.1000238,0,
783,Clinical and molecular study of NPC in Iran: Report of 5 novel mutations,"Niemann–Pick disease type C (NPC) is a rare autosomal, recessive, neurovisceral disorder caused by mutations in the NPC1 (95%) or NPC2 (5%) genes. NPC disease has a variable phenotype, whereby an alteration in cholesterol and glycolipid homeostasis leads to a broad spectrum of symptoms that include hepatosplenomegaly, liver dysfunction, and neurological abnormalities such as progressive ataxia, cataplexy, vertical supranuclear gaze palsy, seizures, and impairment of swallowing reflexes. NPC is rarely reported in Iran and during eighteen months ago,15 patients were diagnosed as NPC by Filipin staining in our department. RT-PCR and sequencing methods were used for molecular investigation for NPC1 and NPC2 genes in 5 patients. All of the five patients (2 female and 3 male) had juvenile form of NPC and had been presented with gait ataxia and so all of them were product of consanguineous marriage too. Case I: 15 years old boy who had hepatosplenomegaly and jaundice in neonatal period. Liver biopsy at that time was compatible with a lipid storage disease. He had supra vertical gaze palsy in 11 years of age and developed progressive ataxia, dystonia and gelastic cataplexia since two years ago.Brain MRI was normal. Case II: 3.5 years old boy, splenomegaly was detected at 6 month of age. He had psychomotor developmental delay .he still can’t walk, he developed supra vertical gaze palsy and gelastic cataplexia (even when he is in a sitting position) since one years ago. Brain MRI was normal. Case III. IV: Two sister, aged 13,17 years old,product of consanguineus marriage;13 years old sister was presented with chief complaint of progressive ataxia and dysarthria since 9th years of age. Since 11th.years of age progressive dysphagia started but now dysphagia is in a plateau state. Cognitive state remains unchanged. She has no seizure nor gelastic cataplexia. There was no history of neonatal jaundice and no splenomegaly was detected. In neurologic examination she had supra vertical gaze palsy. Brain MRI showed nonspecific hypersignal changes in white matter. 17 years old sister had epistaxia at 6th. Year of age and in the work up splenomegaly was detected. Progressive ataxia and dysphagia developed at 7th years of age leading to wheelchair bound state and nasogastric tube feeding at 14 years of age. She died few months ago. Brain MRI showed cerebellar atrophy. In neurologic examination she had supra vertical gaze pulsy. Case V: 13-year-old boy, who presented primarily with neurologic symptoms. He started to develop ataxia and dysarthria at the age of eight years. Dementia, dysphagia, d and seizures, in that sequence, followed within a couple of years. He was anarthric and bedridden four years after onset. Supranuclear vertical gaze palsy was found at the time of the exam. However, no hepatosplenomegaly or other physical abnormality was noted. Whole transcribed exons of the NPC1 genes were sequenced and we could find four different unreported homozygous mutations [Case I: (c.1069C>T) p.S357L, Case II: (c.1180C>T) p.Y394H, Case III. IV: (c.1433A>C) p.N 478 T, Case V: (c.1192C>T) p.H398Y]. All of the mutations were software analyzed and were missense mutations.",adolescent;ataxic gait;cataplexy;cerebellum atrophy;child;clinical article;clinical trial;consanguineous marriage;dementia;developmental disorder;DNA transcription;dysarthria;dysphagia;dystonia;exon;female;gaze paralysis;gene frequency;hepatosplenomegaly;homozygosity;human;immobility;Iran;juvenile;limited mobility;lipidosis;liver biopsy;male;missense mutation;neurologic examination;newborn jaundice;newborn period;nose feeding;nuclear magnetic resonance imaging;preschool child;reverse transcription polymerase chain reaction;school child;seizure;sister;computer program;splenomegaly;white matter;endogenous compound,"Tonekaboni, S. H.;Aryani, O.;Karimzadeh, P.;Zaman, T.;Ashrafi, M. R.;Salehpour, S.;Dehghan Manshadi, M.;Khalili E, E.;Houshmand, M.",2015,,,0,
784,Acute disseminated encephalomyelitis (ADEM) after allogeneic bone marrow transplantation for acute myeloid leukemia,"Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system. We describe here a patient who developed ADEM after allogeneic bone marrow transplantation (BMT). A 48-year-old woman with acute myeloid leukemia (M2) underwent allogeneic BMT from her HLA-identical sister. Cyclosporin for prophylaxis of acute graft-versus-host disease (GVHD) was discontinued from day 15 because of its toxicity. She was relatively well after the resolution of cytomegalovirus reactivation and chronic GVHD. Nine months after BMT, she suddenly developed diplopia, dysarthria, and gait disturbance. Computed tomography of the brain at that time revealed no abnormal findings. Leukemia recurrence was not revealed. The neurological symptoms were very mild without further deterioration. Her clinical course was carefully watched without therapy. Two weeks after onset, fluid attenuated inversion recovery magnetic resonance imaging (MRI) revealed multifocal abnormal high-signal intensity mainly in the white matter of the cerebrum as well as in the cerebellum and brainstem. Cerebrospinal fluid examination showed no abnormal findings. No laboratory findings suggested the presence of infectious agents. The typical MRI findings and an acute monophasic clinical course of this patient led to a diagnosis of ADEM. Twelve weeks after onset, the symptoms had almost resolved. Follow-up MRI showed a substantial improvement of the previous lesions without any new lesions. The symptoms had completely resolved 5 months after onset. This is a rare case of ADEM developing after allogeneic BMT.",,"Tomonari, A.;Tojo, A.;Adachi, D.;Iseki, T.;Ooi, J.;Shirafuji, N.;Tani, K.;Asano, S.",2003,1,,0,
785,An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated cardiomyopathy,"We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with dilatated cardiomyopathy. A 29-year-old male patient first noticed night-blindness at the age of four years. He was pointed out retinitis pigmentosa at the age of six years and developed ataxia, mental retardation, epilepsy and myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum, brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted MRI showed mild high signal intensity in the white matter around the trigones of the lateral ventricles. Autopsy findings showed an abundant accumulation of ceroid-lipofuscin-like lipopigments in most neurons in the central nervous system, and curvilinear bodies and lipofuscin like granules were confirmed by electron microscopy. The heart muscle showed an increase in the accumulation of ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in the myocardium. The peculiar point of this case is NCL3 with dilated cardiomyopathy.",ceroid;lipofuscin;adult;article;ataxia;autopsy;brain atrophy;brain stem;brain ventricle dilatation;case report;cerebellum atrophy;clinical feature;electrocardiogram;electron microscopy;epilepsy;genetic analysis;heart dilatation;heart muscle;heart muscle fibrosis;human;lipid storage;male;mental deficiency;myoclonus;neuronal ceroid lipofuscinosis;night blindness;nuclear magnetic resonance imaging;retinitis pigmentosa;white matter,"Tomiyasu, H.;Takahashi, W.;Ohta, T.;Yoshii, F.;Shibuya, M.;Shinohara, Y.",2000,,,0,
786,[Distribution of ischemic leukoaraiosis in MRI: a difference from white matter lesions in CADASIL],"Previously, the distribution of white matter lesions in CADASIL has been reported to be distinct from those in patients with ischemic leukoaraiosis and Binswanger's disease. In earlier European studies, diagnostic significance of white matter lesions in the temporopolar region (Tp), medial frontopolar region (Fp) and external capsule (EC) was stressed in diagnosing CADASIL. More recently, however, high sensitivity and specificity of Tp lesions have been demonstrated. In Japan, prevalence of CADASIL is lower, and those of ischemic leukoaraiosis and Binswanger's disease, likely related to small artery disease, are much higher than in Caucasian countries. Therefore, we examined the frequencies of CADASIL-associated lesions in 17 non-demented patients with ischemic leukoaraiosis and 20 patients with Binswanger's disease. The Binswanger's disease group showed a significantly lower scores for Hasegawa Dementia Rating Scale Revised (HDSR) and a higher prevalence of hypertension, compared to the ischemic leukoaraiosis group. There was only 1 patient with Tp lesions in each group, while Fp lesions were found in 12 % and 50% in the ischemic leukoaraiosis group and Binswanger's disease group, respectively, and EC lesions in 59% and 80%. These results indicated that Tp lesions were useful diagnostic marker in diagnosing CADASIL, whereas Fp and EC lesions were non-specifically observed.","Brain Ischemia/complications;CADASIL/*diagnosis;Dementia, Vascular/diagnosis;Diagnosis, Differential;Humans;Leukoaraiosis/*diagnosis/physiopathology;*Magnetic Resonance Imaging;Sensitivity and Specificity","Tomimoto, H.;Ohtani, R.;Wakita, H.;Lin, J. X.;Miki, Y.;Mizuno, T.",2005,Feb,,0,
787,"Small artery dementia in Japan: radiological differences between CADASIL, leukoaraiosis and Binswanger's disease","CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small artery disease which is phenotypically similar to Binswanger's disease (BD), a nonhereditary form of small artery disease. Recent studies have indicated that lesions in the temporopolar, medial frontopolar areas and external capsule are frequently seen in Caucasian patients with CADASIL. However, it remains unclear whether magnetic resonance (MR) imaging findings are helpful in diagnosing small artery disease outside countries with Caucasian populations, since CADASIL is rare despite the high prevalence of small artery disease in Japan. We examined 58 patients with small artery disease, all of whom were devoid of major vessel occlusion or severe stenosis. These patients included 7 patients from 3 families with CADASIL, 27 nondemented patients with extensive leukoaraiosis (LA) and 24 patients with BD. On T(2)-weighted MR images, hyperintensities in the temporopolar areas were observed in all 7 patients with CADASIL, whereas these lesions were observed in only 1 subject from each of the nondemented LA and BD groups. Hyperintensities in the medial frontopolar areas were seen in 4 of the 7 patients with CADASIL (57%) and in 14 of the 24 patients with BD (58%), and were more frequent than in the nondemented LA group (4 of the 27 patients; 15%). In contrast, hyperintensities in the external capsule were frequently observed in all groups. Therefore, temporopolar lesions can also serve as diagnostic markers for CADASIL in non-Caucasian patients.","Adult;Aged;Aged, 80 and over;Asian Continental Ancestry Group/ genetics;Brain/ pathology;Brain Stem/pathology;CADASIL/genetics/ radiography;Cross-Cultural Comparison;Dementia, Vascular/ diagnosis/genetics;Diagnosis, Differential;European Continental Ancestry Group/ genetics;Female;Frontal Lobe/pathology;Humans;Image Processing, Computer-Assisted;Leukoaraiosis/ diagnosis/genetics;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology;Pedigree;Sensitivity and Specificity;Temporal Lobe/pathology","Tomimoto, H.;Ohtani, R.;Wakita, H.;Lin, J. X.;Ihara, M.;Miki, Y.;Oshima, F.;Murata, T.;Ishibashi, K.;Suenaga, T.;Mizuno, T.",2006,,10.1159/000090677,0,
788,Different mechanisms of corpus callosum atrophy in Alzheimer's disease and vascular dementia,"Previous neuroimaging studies have indicated that corpus callosum atrophy in Alzheimer's disease (AD) and large vessel occlusive disease (LVOD) is caused by interhemispheric disconnection, namely Wallerian degeneration of interhemispheric commissural nerve fibers originating from pyramidal neurons in the cerebral cortex. However, this hypothesis has not been tested from a neuropathological viewpoint. In the present study, 22 brains with AD (presenile onset, 9; senile onset, 13), 6 brains with Binswanger's disease (BD), a form of vascular dementia and 3 brains with LVOD were compared with 6 non-neurological control brains. White matter lesions in the deep white matter and corpus callosum were quantified as a fiber density score by image analysis of myelin-stained sections. Axonal damage and astrogliosis were assessed by immunohistochemistry for amyloid precursor protein and glial fibrillary acidic protein, respectively.The corpus callosum thickness at the anterior part of the body was decreased in AD and LVOD,but not in BD significantly, as compared with the controls. The corpus callosum thickness correlated roughly with brain weight in AD (R=0.50),and with the severity of deep white matter lesions in BD (R=0.81). Atrophy of the brain and corpus callosum was more marked in presenile onset AD than in senile onset AD. With immunohistochemistry, the corpus callosum showed axonal damage and gliosis with a decreased fiber density score in BD and LVOD, but not in AD. Thus, corpus callosum atrophy was correlated with brain atrophy in AD, which is relevant to the mechanism of interhemispheric disconnection,whereas corpus callosum lesions in BD were secondary to deep white matter lesions. Corpus callosum atrophy in LVOD may indicate interhemispheric disconnection, but focal ischemic injuries may also be involved.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Analysis of Variance;Atrophy;Corpus Callosum/ pathology;Dementia, Vascular/ pathology;Female;Humans;Male;Middle Aged","Tomimoto, H.;Lin, J. X.;Matsuo, A.;Ihara, M.;Ohtani, R.;Shibata, M.;Miki, Y.;Shibasaki, H.",2004,Apr,10.1007/s00415-004-0330-6,0,
789,Subinsular vascular lesions: An analysis of 119 consecutive autopsied brains,"The insula of Reil constitutes a functionally intriguing complex of the brain related to multifunctional activities. We examined the subinsular region in 119 consecutively autopsied patients, as T2 hyperintense lesions are frequently observed in magnetic resonance diagnosis of this region. The patients were admitted in neurology wards and were diagnosed as having cerebrovascular disease in 55 patients (46%), other neurological diseases in 57 patients (48%) and non-neurological diseases in seven patients (6%). Demyelination of the white matter was semi-quantified as a fiber density score (percent stained area/total area) with computer-assisted image analysis on Klüver-Barrera-stained sections. Astrogliosis was assessed by immunohistochemistry for glial fibrillary acidic protein. The lesion analysis showed a dilated perivascular space in 29 patients (24%), demyelination (fiber density score less than the mean - 1 SD) in 27 patients (23%), slit-shaped lesion in six patients (5%), lacunar infarction in one patient (1%) and cerebral hemorrhage in one patient (1%). A histologic-radiologic comparison in two patients with subcortical ischemic vascular dementia showed correspondence between subinsular hyperintensities, and demyelination, gliosis and a dilated perivascular space. These results indicate that subinsular lesions rarely signifies focal vascular lesions, and are consisted of demyelination, gliosis and a dilated perivascular space. © 2007 EFNS.",,"Tomimoto, H.;Lin, J.;Ihara, M.;Ohtani, R.;Matsuo, A.;Miki, Y.",2007,January,,0,
790,The coagulation-fibrinolysis system in patients with leukoaraiosis and binswanger disease,"Background: Hypercoagulability is observed in vascular dementia, including Binswanger disease. However, the correlation between hypercoagulability, leukoaraiosis, and dementia remains unclear. Objective: To examine how activation of the coagulation fibrinolysis correlates with leukoaraiosis and dementia. Patients and Methods: Thrombin-antithrombin complex (TAT), prothrombin fragment(1+2) (F (1+2))and cross-linked D-dimer (XDP) were measured consecutively in 18 subjects without dementia and with leukoaraiosis, and in 29 subjects with subcortical vascular dementia and severe leukoaraiosis (Binswanger disease) at either stable or deteriorating stages. They were compared with 19 patients with old lacunar infarctions and 24 patients with other neurological diseases. We also examined the indices of cognitive impairment and brain atrophy. In each group, the ventricular area-cranial space area ratio was measured by an image analyzer. Results: Patients with Binswanger disease who were exclusively at deteriorating stages showed increased TAT and XDP levels and an increased ventricular areacranial space area ratio, as compared with the patients with other neurological diseases (P>.001). The index of cognitive impairment in patients at a deteriorating stage showed a decreasing trend vs that of patients in the stable stage. Among the variables that were significantly associated with a hypercoagulable condition (ie, age, scores on Mini-Mental State Examination or the Hasegawa Dementia Rating Scale, Revised [MMSE/HDRS], white matter lesions, ventricular area-cranial space area ratio, and C-reactive protein), age (odds ratio [OR], 2.82) and MMSE/HDSR scores (OR, 0.43) survived as predictors for coagulation activation, and C-reactive protein survived for fibrinolysis activation (OR, 4.63) in multivariate analysis. Conclusion: Hypercoagulability in a subgroup of patients with Binswanger disease and with more severe cognitive impairment and brain atrophy does not support a triggering role for a coagulation-fibrinolysis system, although it may contribute to worsening of neurological deficits.",,"Tomimoto, H.;Akiguchi, I.;Ohtani, R.;Yagi, H.;Kanda, M.;Shibasaki, H.;Yamamoto, Y.",2001,2001,,0,
791,Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report,"Background and purpose: Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. Methods: Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. Results: Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. Conclusions: Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management. © 2009 Elsevier B.V. All rights reserved.",adult;article;brain infarction;case report;clinical feature;dysarthria;dysphasia;dysphonia;human;language disability;male;neuropathology;nuclear magnetic resonance imaging;priority journal;speech analysis;speech disorder;white matter,"Tomić, G.;Stojanović, M.;Pavlović, A.;Stanković, P.;Zidverc-Trajković, J.;Pavlović, D.;Marković-Jovanović, Z.;Čovičković-Šternić, N.",2009,,,0,
792,Everyday functioning in relation to cognitive functioning and neuroimaging in community-dwelling hispanic and Non-Hispanic older adults,"The purpose of this study was to examine how a specific informant-based measure of everyday functioning, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE; Jorm & Korten, 1988) relates to cognition and structural neuroimaging in a large multicultural, multilingual sample of Caucasians and Hispanics. Cognitive variables included selected subtests from the Spanish and English Neuropsychological Assessment Scales (SENAS; Mungas et al., 2000): Verbal Memory, Object Naming, Verbal Attention Span, Verbal Conceptual Thinking, and Pattern Recognition. The association between the IQCODE and selected neuroimaging variables, hippocampal volume and white matter hyperintensity, was evaluated in a subsample of English- and Spanish-speaking Hispanic individuals. The cognitive variables showed strong bivariate relationships with the IQCODE, although only Verbal Memory and Object Naming independently predicted level of functional ability. Verbal Memory was the strongest predictor of functional status, accounting for 23% of the variance in the IQCODE. White matter hyperintensity was also independently related to the IQCODE, accounting for 18% of the variance. Hippocampal volume was related to the IQCODE in a simple bivariate analysis, but was not an independent predictor of reported functional status after controlling for age. The relationships between cognitive variables and functional status, as well as between the imaging variables and the IQCODE, did not differ across language-ethnic groups. Copyright © 2004 INS.",,"Tomaszewski Farias, S.;Mungas, D.;Reed, B.;Haan, M. N.;Jagust, W. J.",2004,May,,0,
793,Parkinsonism and basal ganglia infarcts,"A subacute parkinsonian syndrome was seen in three patients with CT evidence of basal ganglia infarcts. The clinical picture improved spontaneously, making the diagnosis of idiopathic Parkinson's disease untenable, and other causes of parkinsonism were not detected. This extrapyramidal syndrome was therefore compatible with 'vascular parkinsonism', even though it lacked features often ascribed to this syndrome, such as a history of previous strokes and the presence of dementia and corticospinal tract signs.",basal ganglion;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;etiology;human;infarction;major clinical study;parkinsonism;peripheral vascular system;pyramidal tract,"Tolosa, E. S.;Santamaria, J.",1984,,,0,
794,Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI,"Previous studies of Aβ plasma as a biomarker for Alzheimer's disease (AD) obtained conflicting results. We here included 715 subjects with baseline Aβ1-40 and Aβ1-42 plasma measurement (50% with 4 serial annual measurements): 205 cognitively normal controls (CN), 348 patients mild cognitive impairment (MCI) and 162 with AD. We assessed the factors that modified their concentrations and correlated these values with PIB PET, MRI and tau and Aβ1-42 measures in cerebrospinal fluid (CSF). Association between Aβ and diagnosis (baseline and prospective) was assessed. A number of health conditions were associated with altered concentrations of plasma Aβ. The effect of age differed according to AD stage. Plasma Aβ1-42 showed mild correlation with other biomarkers of Aβ pathology and were associated with infarctions in MRI. Longitudinal measurements of Aβ1-40 and Aβ1-42 plasma levels showed modest value as a prognostic factor for clinical progression. Our longitudinal study of complementary measures of Aβ pathology (PIB, CSF and plasma Aβ) and other biomarkers in a cohort with an extensive neuropsychological battery is significant because it shows that plasma Aβ measurements have limited value for disease classification and modest value as prognostic factors over the 3-year follow-up. However, with longer follow-up, within subject plasma Aβ measurements could be used as a simple and minimally invasive screen to identify those at increased risk for AD. Our study emphasizes the need for a better understanding of the biology and dynamics of plasma Aβ as well as the need for longer term studies to determine the clinical utility of measuring plasma Aβ. © 2011 Springer-Verlag.",amyloid beta protein[1-40];amyloid beta protein[1-42];tau protein;adult;age;aged;Alzheimer disease;article;brain infarction;controlled study;disease course;disease marker;female;human;longitudinal study;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;positron emission tomography;priority journal;prognosis;protein blood level;protein cerebrospinal fluid level,"Toledo, J. B.;Vanderstichele, H.;Figurski, M.;Aisen, P. S.;Petersen, R. C.;Weiner, M. W.;Jack Jr, C. R.;Jagust, W.;Decarli, C.;Toga, A. W.;Toledo, E.;Xie, S. X.;Lee, V. M. Y.;Trojanowski, J. Q.;Shaw, L. M.",2011,,,0,
795,A case of the persistent vegetative state following symmetrical peduncular infarction,"A 64-year-old woman presented with sudden onset of disequilibrium and dysarthria. Two days later she became lethargic and tetraparetic. An emergency MRI disclosed multiple infarctions in the medulla oblongata and pons. An angiogram revealed severe stenosis of the rostral basilar artery. The patient underwent a rapidly progressive course with impaired consciousness and flaccid tetraplegia. MR images 7 days after the onset disclosed a symmetrical midbrain infarction that was localized mainly in the cerebral peduncles, suggesting a distal basilar artery occlusion as the cause of this pathology. Since 4 weeks after the onset the pa- tient was in the persistent vegetative state, which was essentially unchanged during the 1-year follow-up period. Persistent vegetative state is known to be caused by diffuse supratentorial or bilateral thalamic lesions, but in our case the lesions were restricted to the infratentorial area. We speculate a mechanism to cause the persistent vegetative state by partial impairment of the connection to the thalamic ascending system or extra-thalamic ascending system, which leads to the dissociation of arousal (preserved in this case) and awareness (impaired in this case) after the ventral midbrain infarction.",,"Tokunaga, T.;Kita, Y.;Yamamoto, T.",2002,2002,,0,
796,Imaging-pathologic correlation in corticobasal degeneration,"BACKGROUND AND PURPOSE: The clinical diagnosis of corticobasal degeneration (CBD) is often difficult due to varied clinical manifestations. In 4 patients with neuropathologically confirmed CBD, characteristic imaging findings and correlations with neuropathologic features were evaluated. Furthermore, imaging findings in CBD were compared with neuropathologically confirmed progressive supranuclear palsy (PSP) for a differential diagnosis. MATERIALS AND METHODS: Four patients with neuropathologically confirmed CBD were studied. We evaluated the area of the tegmentum in the midsagittal plane, subcortical white matter (SCWM) abnormality, asymmetric cerebral atrophy, and signal-intensity abnormality in the subthalamic nuclei on MR imaging and compared them with histopathologic findings. Then, MR imaging findings in CBD were compared with those in 13 patients with PSP. RESULTS: On MR imaging, 3 patients had asymmetric cerebral atrophy extending to the central sulcus. On midsagittal sections, the mean midbrain tegmentum area was 66 mm(2), being markedly smaller than normal, but there was no significant difference between PSP and CBD. All patients had signal-intensity abnormalities of the SCWM, constituting primary degeneration neuropathologically; however, no diffuse signal-intensity abnormality in the SCWM existed in the 13 patients with PSP. In 3 patients, T1-weighted images showed symmetric high signal intensity in the subthalamic nuclei. Neuropathologically, these areas showed characteristic CBD. MR imaging signal-intensity changes also existed in 4 patients with PSP; however, subthalamic nucleus degeneration was more severe in PSP than in CBD. CONCLUSIONS: In cases with midbrain tegmentum atrophy and signal-intensity changes in the subthalamic nuclei, the differential diagnosis distinguishing CBD from PSP based on MR imaging alone was difficult. White matter lesions and asymmetric atrophy can be useful for a differential diagnosis.",,"Tokumaru, A. M.;Saito, Y.;Murayama, S.;Kazutomi, K.;Sakiyama, Y.;Toyoda, M.;Yamakawa, M.;Terada, H.",2009,November-December,,0,
797,Virchow-Robin spaces in cerebral imaging: Relationship of differential diagnosis and clinical findings,"Background: Enlarged perivascular space which is lined with pia and surrounding the penetrating small arteries and arterioles of the brain is called Virchow-Robin Space (VRS). The typical localization for VRBs is around the anterior commisure area close to vertex, however VRBs in other parts can be visualized with high resolution techniques. Although the etiological factors regarding VTS is not clear, Virchow-Robin spaces were detected in patients with dementia, epilepsy, head trauma, high blood pressure. Furthermore they may cause obstructive hydrocephalus. The differential diagnosis of VRB includes lacunar infarcts, demyelinating lesions, vasculitis and tumors. Cases: In the first case who was complaining of vertigo, MRI disclosed ovoid lesions which were isointense with cerebrospinal fluid and located in periventricular, right posterior parietal and occipital areas. These lesions were not relevant with the clinical findings and considered coincidental. Second case had truncal ataxia, flapping tremor, myoclonus, and loss of position and vibration senses. MRI revealed atrophy and multiple infarctions of cerebrum and cerebellum in addition to multiple large perivascular spaces located in bilateral lentiform nuclei, caudate heads and thalami. It was impossible to establish etiological relationship between the radiological and clinical findings. Third case was an epileptic patient. There were chronic ischemic lesions located in deep and subcortical white matter, besides VRBs in centrum semiovale, thalamus, and basal ganglia. Conclusion: Although it was impossible to reach a certain etiological relationship between clinical and radiological findings in this limited number of patients, the findings might be a contribution to knowledge about the VRS.",,"Tokuçoǧlu, F.;Arici, Ş;Çelebisoy, M.;Yildiz, B.;Kaplangi, N. D.;Özer, B.",2009,April,,0,
798,Age-dependent cognitive and affective differences in Alzheimer's and Parkinson's diseases in relation to MRI findings,"OBJECTIVE: To compare age-dependent changes in cognitive and affective functions related to white matter changes between patients with Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: We retrospectively compared age-dependent cognitive and affective functions in 216 AD patients, 153 PD patients, and 103 healthy controls with cerebral white matter lesions (WMLs), periventricular hyperintensity (PVH), deep white matter hyperintensity (DWMH), micro-bleeds (MBs), and lacunar infarcts (LIs). RESULTS: The average mini-mental state examination (MMSE) scores were 19.6+/-6.1 and 26.8+/-3.6 in AD and PD patients, respectively. Significant decreases were found in the MMSE score, Hasegawa's dementia scale-revised (HDS-R) score, frontal assessment battery score, and Abe's BPSD score (ABS) among the age-dependent AD subgroups and in the MMSE, HDS-R, Montreal cognitive assessment, geriatric depression scale, and ABS scores among the age-dependent PD subgroups; they were worse in AD patients. White matter changes were observed in >88% and >72% of patients with AD and PD, respectively. An age-dependent direct comparison of AD and PD showed significant differences in the PVH and DWMH grades, and numbers of MBs and LIs. CONCLUSION: WML-related cognitive and affective functions worsen with age in AD and PD patients; however, the abnormalities were more frequent and stronger in AD patients.",Affective function;Alzheimer's disease;Cognitive function;Parkinson's disease;White matter lesion,"Tokuchi, R.;Hishikawa, N.;Sato, K.;Hatanaka, N.;Fukui, Y.;Takemoto, M.;Ohta, Y.;Yamashita, T.;Abe, K.",2016,Jun 15,10.1016/j.jns.2016.03.031,0,
799,Clinical and demographic predictors of mild cognitive impairment for converting to Alzheimer's disease and reverting to normal cognition,"OBJECTIVE: To identify clinical and demographic predictors for mild cognitive impairment (MCI) conversion to Alzheimer's disease (AD) or reversion to normal cognition, and sustained MCI. METHODS: In total, 74 baseline MCI subjects were retrospectively investigated and categorized into three subgroups: conversion to AD, sustained MCI, or reversion to normal cognition during one year. The clinical and demographic characteristics assessed were age, gender, educational attainment, vascular risk factors, white matter lesions (WMLs), and parahippocampal gyrus atrophy (PGA), analyzed by magnetic resonance imaging (MRI) using the voxel-based specific regional analysis system for AD (VSRAD). RESULTS: Of the 74 MCI subjects, 29 (39.2%) were classified as ""converters"", 39 (52.7%) as ""sustained MCI"", and 6 (8.1%) as ""reverters"". Among the three subgroups, there were significant differences in educational attainment (years) (*p = 0.03), baseline mini-mental state examination (MMSE) scores (***p<0.001), and periventricular and deep white matter hyperintensity grades (*p = 0.02 and *p = 0.03, respectively). Baseline PGA showed a significant increasing trend among the three subgroups (reverters<sustained MCI<converters, (###)p<0.001). MCI subjects with higher educational attainment and low VSRAD Z-scores without WMLs were associated with reversion to normal cognitive function. CONCLUSIONS: Risk factors for MCI conversion to AD were low educational attainment, low baseline MMSE scores, high grade WMLs, and high VSRAD Z-scores. High educational attainment, low VSRAD Z-scores, and no WMLs characterized reversion to normal cognition.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Atrophy/pathology;Brain/ pathology;Cognition/ physiology;Disease Progression;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/pathology;Neuropsychological Tests;Prognosis;Retrospective Studies;Risk Factors","Tokuchi, R.;Hishikawa, N.;Kurata, T.;Sato, K.;Kono, S.;Yamashita, T.;Deguchi, K.;Abe, K.",2014,Nov 15,10.1016/j.jns.2014.09.012,0,
800,[Impact of combined medial temporal atrophy and white matter lesions on the cognitive and emotional functions in Alzheimer's disease patients],"AIM: The purpose of this study was to determine the relationship between the combined presence of medial temporal atrophy (MTA) and white matter lesions (WMLs: periventricular hyperintensity (PVH) and deep white matter hyperintensity) and the cognitive/emotional function in Alzheimer's disease (AD) patients. METHODS: The subjects included 193 patients with AD and 30 normal elderly controls. On MRI, MTA was rated using the Voxel-based specific regional analysis system for AD (VSRAD). WMLs was also estimated using the Fazekas scale. The MRI measurements were classified as follows: MTA=VSRAD<2 or >/=2; WML absent (-) 0/1 or present (+) 2/3. A total of five groups were assessed, including four groups with AD and a control group. The cognitive and emotional functions were evaluated with neuropsychological tests (Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS) and Apathy scale). RESULTS: Four AD groups showed significant declines in the both the MMSE and FAB scores compared to that observed in the control group ((***)p<0.001, (**)p<0.01, (*)p<0.05). Among these four AD groups, the MMSE and FAB scores of in the VSRAD<2 and WML (-) groups significantly declined to VSRAD>/=2 and WML (+), respectively group ((*)p<0.05). VSRAD>/=2 and WML (+) groups showed demonstrated significantly higher scores than the control group on the GDS ((*)p<0.05), and the PVH (+) group exhibited significantly higher scores than the control group on the apathy scale ((*)p<0.05). Multiple regression analysis identified a VSRAD score of >/=2 and the presence of WMLs to be most significantly associated with the cognitive and emotional functions. CONCLUSIONS: Combined presence of MTA and WML is associated with lower MMSE and FAB scores. Furthermore, depression is also associated with MTA and WML, while PVH independently affects the degree of apathy.",,"Tokuchi, R.;Deguchi, K.;Yamashita, T.;Abe, K.",2014,,,0,
801,"A case of idiopathic brain calcification associated with dyschromatosis symmetrica hereditaria, aplasia of dental root, and aortic valve sclerosis","The patient was a 23-year-old woman. She was the product of a full-term pregnancy and normal delivery. At age 3, she was observed to have eruptions on the face and extremities. Gait disturbance and abnormal posture appeared when she was 17-year-old. Mental deterioration followed several years later, and these symptoms progressed gradually. On examination at age 23, mixture of hyperpigmented and hypopigmented macules were observed on the face and the dorsal aspects of the extremities. We diagnosed her skin lesion as dyschromatosis symmetrica hereditaria (DSH) based on dermatological findings, normal minimal erythema dose and normal unscheduled DNA synthesis of her skin fibroblasts. Neurologically, she showed moderate mental deterioration, dystonic posture, dystonic and spastic gait, and generalized hyperreflexia. Laboratory examinations, including parathyroid function, were normal. Brain CT scan revealed severe symmetrical calcifications in the basal ganglia, cerebral white matter, and dentate nucleus. She also showed aplasia of dental root and aortic valve sclerosis. Her father also revealed the same clinical features including skin lesion, movement disorder, mental deterioration, and severe aortic valve calcification. So we diagnosed this patient as familial idiopathic brain calcification associated with DSH, aplasia of dental root, and aortic valve sclerosis. Constellation of these clinical features does not match any previously established type of familial idiopathic brain calcification or hereditary dystonia. However, Patrizi et al reported a patient with DSH associated with torsion dystonia who was very similar to our patient. We propose that our patient and the patient reported by Patrizi et al construct a distinct clinical entity in familial idiopathic brain calcification or hereditary dystonia.",adult;aorta valve disease;article;brain calcification;case report;color vision defect;disease association;dystonia;female;gait disorder;human;mental deterioration;motor dysfunction;tooth malformation;tooth root,"Tojyo, K.;Hattori, T.;Sekijima, Y.;Yoshida, K.;Ikeda, S. I.",2001,,,0,
802,Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy with a Novel NOTCH3 Cys323Trp Mutation Presenting Border-Zone Infarcts: A Case Report and Literature Review,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary and progressive small-vessel disease caused by NOTCH3 mutations, pathologically characterized by the degeneration of vascular mural cells, white matter changes, and ischemic strokes. Recently, dysautoregulation has received increasing attention regarding the pathogenesis of stroke in CADASIL. Here, we report a CADASIL case with a novel Cys323Trp mutation in the NOTCH3 gene, which suggests a close relationship between hemodynamic factors and clustering of cerebral infarctions in CADASIL. A 47-year-old male patient presented with internal border-zone infarcts in the bilateral hemispheres and was diagnosed with CADASIL by the presence of granular osmiophilic material and the accumulation of the Notch3 extracellular domain around small vessels. A literature review revealed 7 reports of similar CADASIL cases with clustering of cerebral infarctions related to blood pressure fluctuations. Not only large-artery stenosis but also small-vessel pathologies potentiate watershed infarctions, which might be triggered by hemodynamic fluctuation due to cerebral dysautoregulation.",cystine;Notch3 receptor;olmesartan;osmium;tryptophan;adult;article;ataxic aphasia;CADASIL;case report;diffusion weighted imaging;echography;electron microscopy;faintness;gene mutation;hemiplegia;human;hypertension;hypotension;immunohistochemistry;male;medical history;middle aged;neuroimaging;nuclear magnetic resonance imaging;physical examination;priority journal;protein domain;skin biopsy;transesophageal echocardiography,"Tojima, M.;Saito, S.;Yamamoto, Y.;Mizuno, T.;Ihara, M.;Fukuda, H.",2016,,10.1016/j.jstrokecerebrovasdis.2016.05.013,0,
803,A Case of Bilateral Paramedian Thalamic Infarction in Childhood with the Sensory Disturbance and the Sensory Loss of Taste,"Bilateral paramedian thalamic infarcts are characterized by disturbance of consciousness, followed by persisting dementia, decreased spontaneity, apathy, amnesia and paralysis of eye movement. We report a 15-year-old boy with this syndrome, who exhibited transient coma at the onset. In addition to the typical symptoms, he complained of sensory disturbance in the lower extremities and face and the loss of taste sense. MRI showed symmetric paramedian thalamic infarction. There was no lesion in the midbrain. The etiology of infarct in this boy remained unknown despite extensive laboratory and neuroradiological examination. His sensory disturbance in the extremities and face may be due to extensive involvement of the inferolateral area of the thalamus by infarction of the paramedian thalamic artery. This patient illustrates that bilateral paramedian thalamic infarction can occur in a previously healthy child.",adolescent;amnesia;apathy;article;brain infarction;case report;coma;consciousness disorder;dementia;disease association;eye movement;human;laboratory test;male;mesencephalon;neuroradiology;nuclear magnetic resonance imaging;paralysis;sensory dysfunction;symptomatology;taste disorder;thalamus,"Tohyama, J.;Kanazawa, O.;Akasaka, N.;Kamimura, T.",2004,,,0,
804,Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes,"Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO2 and rCBV were determined using C15O2, 15O2 and C15O, respectively. rCBF and CMRO2 were significantly decreased in the frontal, parietal and temporal cortex (P < 0.05) in patients with SDAT, and showed a significant correlation with the severity of dementia (P < 0.05). In patients with DWMH rCBF was significantly decreased in the parietal cortex and in the frontal white matter in nondemented patients, and in the cerebral cortex and white matter of most regions studied in demented patients (P < 0.05), whereas rCMRO2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. These results suggest that rOEF is increased in both SDAT and patients with DWMH. The increase in rOEF in patients with SDAT may be accounted for by reduction in rCBV resulting from decreased activity in the vasodilatory cholinergic system, impairment of glucose metabolism and white matter changes; the rOEF increase in patients with DWMH suggests relative preservation of oxidative metabolism compared to disturbed perfusion.","Aged;Alzheimer Disease/physiopathology/*radionuclide imaging;Brain/metabolism/pathology/*radionuclide imaging;Case-Control Studies;Cerebrovascular Circulation/*physiology;Dementia, Vascular/physiopathology/*radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Oxygen Consumption/*physiology;*Tomography, Emission-Computed","Tohgi, H.;Yonezawa, H.;Takahashi, S.;Sato, N.;Kato, E.;Kudo, M.;Hatano, K.;Sasaki, T.",1998,Mar,,0,
805,"Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings","BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.",,"Tobin, W. O.;Popescu, B. F.;Lowe, V.;Pirko, I.;Parisi, J. E.;Kantarci, K.;Fields, J. A.;Bruns, M. B.;Boeve, B. F.;Lucchinetti, C. F.",2016,Apr,10.1177/1352458515604382,0,
806,Premenopausal hysterectomy is associated with increased brain ferritin iron,"Iron is essential for triggering oligodendrocytes to myelinate, however, in gray matter (GM) iron increases with age and is associated with age-related degenerative brain diseases. Women have lower iron levels than men, both in the periphery and in the brain, particularly in white matter (WM), possibly due to iron loss through menstruation. We tested the hypothesis that hysterectomy could increase WM iron levels. We assessed 3 WM and 5 gray matter regions in 39 postmenopausal women, of whom 15 had premenopausal hysterectomy, utilizing a validated magnetic resonance imaging technique called field-dependent R2 increase (FDRI) that quantifies ferritin iron. A group of 54 matched male subjects was included for comparison. Amongst women, hysterectomy was associated with significantly higher frontal lobe WM iron. Men had higher iron levels than women without hysterectomy in 3 brain regions but did not differ from women with hysterectomy in any region. The results suggest that menstruation-associated blood loss is a source of gender differences in brain iron. It is possible that brain iron can be influenced by peripheral iron levels and may thus be a modifiable risk factor for age-related degenerative diseases. © 2012 Elsevier Inc.",,"Tishler, T. A.;Raven, E. P.;Lu, P. H.;Altshuler, L. L.;Bartzokis, G.",2012,September,,0,
807,Shunt surgery in patients with hydrocephalus and white matter changes,"OBJECT: Patients with idiopathic normal pressure hydrocephalus (iNPH) often present with impaired gait and cognition together with ventricular enlargement and normal intracranial pressure. Many have vascular risk factors as well as periventricular and deep white matter changes on MR imaging. Abnormal CSF dynamics, that is, high resistance to outflow or improvement after CSF drainage, indicate good effects of shunt surgery. The authors examined whether the worst-case iNPH patients with extensive vascular white matter disease and normal CSF dynamics would benefit from shunt surgery. These patients also fulfilled the criteria for Binswanger disease. Therefore, a randomized controlled double-blind study was performed. METHODS: Fourteen consecutive patients fulfilling the above criteria were randomized to receive either open or closed shunts. At 3 months after surgery, the patients with initially ligated shunts had their shunts opened. Clinical evaluation consisting of 7 quantitative psychometric and 6 continuous gait tests was performed preoperatively and 3 and 6 months after surgery. RESULTS: Patients randomized to receive open shunts had improved motor (30% increase) and psychometric (23% increase) scores 3 months after shunt placement. There were no significant changes between the 3- and 6-month follow-up in these same patients. Conversely, those with initially ligated shunts were unchanged during the first 3-month period, although they improved in both motor (28%) and cognitive (18%) functions following removal of the ligature. CONCLUSIONS: Patients with enlarged ventricles, hydrocephalic symptoms, and extensive vascular white matter changes benefit from shunt surgery.","Aged;Aged, 80 and over;Brain/pathology;Cerebrospinal Fluid Pressure/physiology;Comorbidity;Dementia, Vascular/diagnosis/ surgery;Female;Follow-Up Studies;Gait Disorders, Neurologic/etiology;Humans;Hydrocephalus, Normal Pressure/diagnosis/ surgery;Image Processing, Computer-Assisted;Ligation;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination/statistics & numerical data;Neuropsychological Tests/statistics & numerical data;Postoperative Complications/etiology;Psychometrics;Ventriculoperitoneal Shunt","Tisell, M.;Tullberg, M.;Hellstrom, P.;Edsbagge, M.;Hogfeldt, M.;Wikkelso, C.",2011,May,10.3171/2010.11.jns10967,0,
808,Changes in functional organization and white matter integrity in the connectome in Parkinson's disease,"Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional ""disconnection"" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.",Diffusion tensor imaging;Dopamine;Graph theory;Modularity;Neural network;Resting-state fMRI,"Tinaz, S.;Lauro, P. M.;Ghosh, P.;Lungu, C.;Horovitz, S. G.",2017,,,0,
809,New onset seizures in the elderly: aetiology and prognosis,"Late onset epilepsy is increasing in incidence. These patients often have significant underlying morbidity. This retrospective study in a tertiary referral centre identified 68 patients aged 65 years or older, with new onset seizures over a four-year period. 81% of patients (n = 55) were followed up at an average of 2.7 years post diagnosis. 38% of patients had evidence of cerebrovascular disease (CT visualised focal infarction, haemorrhage or small vessel ischaemia in 32%, clinical diagnosis with normal CT brain in 6%). No patient was found to have a space-occupying lesion. Of the 55 patients followed up, 45% of these had died at a mean age of 82 years old and 1.9 years post diagnosis (range 12 hours to 5 years). Three patients died as a direct result of seizures (trauma and sepsis). 14 patients died of clearly unrelated causes. Eight patients died from underlying vascular disease or Alzheimer's dementia. Patients who died during follow-up were on average 3.4 years older at the time of diagnosis than survivors (p< 0.05). Patients with atrial fibrillation at the time of diagnosis, had increased mortality (relative risk 2.53; 95% C.I. 1.19 - 5.36), but they were older than those without atrial fibrillation. At the time of follow up, 92% of those taking anti-convulsants were maintained seizure free on anticonvulsant monotherapy.","Age Factors;Aged;Aged, 80 and over;Anticonvulsants/therapeutic use;Comorbidity;Epilepsy/*epidemiology/etiology/mortality/prevention & control;Follow-Up Studies;Humans;Incidence;Prognosis;Retrospective Studies;Time Factors","Timmons, S.;Sweeney, B.;Hyland, M.;O'Mahony, D.;Twomey, C.",2002,Feb,,0,
810,Coexistence of Alzheimer's disease and multi-infarct dementia diagnosed by functional brain imaging with SPECT,,"Alzheimer Disease/ complications/radionuclide imaging;Amphetamines;Dementia, Multi-Infarct/ complications/radionuclide imaging;Humans;Tomography, Emission-Computed, Single-Photon","Timmons, J. H.;Heironimus, J. D.",1990,Apr,,0,
811,Diffusion tensor imaging of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer's dementia,"Neuropsychiatric symptoms (NPS) occur frequently in mild cognitive impairment (MCI) and Alzheimer's dementia (AD). The authors examined the relationship between NPS and white-matter integrity in these conditions. Twenty-two individuals with MCI and 23 with mild AD underwent clinical assessments including the Neuropsychiatric Inventory Questionnaire and 3.0-tesla magnetic resonance scans. Fractional anisotropy (FA) was measured in the following manually-drawn regions of interest (ROI): fornix, cingulum bundle, splenium, and cerebral peduncles (control region). The probability of having NPS by tertile of ROI FA was assessed by logistic regression. Because associations were similar within MCI and AD groups, the two groups were combined. Compared with those in the highest tertile, participants within the lowest anterior cingulum (AC) FA tertile were more likely to exhibit irritability, agitation, dysphoria, apathy, and nighttime behavioral disturbances. After adjusting for Mini-Mental State Exam status, participants in the lowest versus highest tertile of AC FA were more likely to report irritability. Using DTI, low AC FA was associated with increased odds of irritability in mild AD and MCI participants. Further imaging studies are necessary to elucidate the role of the AC in the pathophysiology of neuropsychiatric symptoms in AD and MCI.","Aged;Aged, 80 and over;Alzheimer Disease/ physiopathology;Anisotropy;Anxiety/ physiopathology;Apathy/ physiology;Brain/ physiopathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Irritable Mood/ physiology;Male;Middle Aged;Mild Cognitive Impairment/ physiopathology;Neuropsychological Tests;Surveys and Questionnaires","Tighe, S. K.;Oishi, K.;Mori, S.;Smith, G. S.;Albert, M.;Lyketsos, C. G.;Mielke, M. M.",2012,Fall,10.1176/appi.neuropsych.11120375,0,
812,Behavioral and psychological symptoms and hippocampal atrophy in subcortical ischaemic vascular disease,"Background: Neuropsychiatric symptoms are common in patients with cognitive impairments, mediated by both neurodegenerative processes and cerebrovascular disease. Previous studies have reported that Behavioral and Psychological Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline. Thus far, the impact of the association between white-matter hyperintensities (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been less studied. Objective: This cross-sectional study aimed to describe the clinical profile of a sample with large extensions of WMH, examining the association between different degrees of HA and cognitive, functional, and behavioral status. Methods: Fifty outpatients (mean age: 76.86+/-8.70 years; 58% female; mean schooling: 7.44+/-4.69 years) with large extensions of WMH (modified-Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according to de Leon Score) underwent cognitive, functional, and behavioral assessments. Results: Patients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffer's Functional Activities Questionnaire, compared to the group with none or questionable HA. Appetite/Eating Behavior was the only cluster of neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive Impairment patients. Discussion: Although HA may exhibit distinct impact on cognitive performance and functional status, it appears to have little effect on behavioral symptoms in patients with high severity WMH.",cerebrovascular disease;executive function;neuroimaging;neuropsychiatry;neuropsychology;vascular dementia,"Tiel, C.;Sudo, F. K.;Alves, C. E. O.;Alves, G. S.;Ericeira-Valente, L.;Moreira, D. M.;Laks, J.;Engelhardt, E.",2012,Jul-Sep,,0,
813,Diabetes increases atrophy and vascular lesions on brain MRI in patients with symptomatic arterial disease,"BACKGROUND AND PURPOSE: Diabetes type 2 (DM2) is associated with accelerated cognitive decline and structural brain abnormalities. Macrovascular disease has been described as a determinant for brain MRI changes in DM2, but little is known about the involvement of other DM2-related factors. METHODS: Brain MRI was performed in 1043 participants (151 DM2) with symptomatic arterial disease. Brain volumes were obtained through automated segmentation. RESULTS: Patients with arterial disease and DM2 had more global and subcortical brain atrophy (-1.20% brain/intracranial volume [95%CI -1.58 to -0.82], P<0.0005 and 0.20% ventricular/intracranial volume [0.05 to 0.34], P<0.01), larger WMH volumes (0.22 logtransformed volume [0.07 to 0.38], P<0.005), and more lacunar infarcts (OR 1.75 [1.13 to 2.69], P<0.01) than identical patients without DM2. In patients with DM2, high glucose levels (B-0.12% per mmol/L [-0.23 to -0.01], P<0.05) and diabetes duration (B-0.05% per year [-0.10 to -0.001], P<0.05) were associated with global brain atrophy. CONCLUSIONS: In patients with symptomatic arterial disease, DM2 has an added detrimental effect on the brain. In patients with DM2, hyperglycemia and diabetes duration contribute to brain atrophy.",aged;atrophy;brain;brain artery;brain atherosclerosis;cerebrovascular disease;cognitive defect;cohort analysis;dementia;disease course;female;human;hyperglycemia;letter;leukoaraiosis;male;middle aged;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;pathology;pathophysiology;prediction and forecasting;prospective study;risk factor;vascularization,"Tiehuis, A. M.;van der Graaf, Y.;Visseren, F. L.;Vincken, K. L.;Biessels, G. J.;Appelman, A. P.;Kappelle, L. J.;Mali, W. P.",2008,,,0,
814,Cognitive dysfunction and its clinical and radiological determinants in patients with symptomatic arterial disease and diabetes,"Background and aims: Both vascular disease and diabetes type 2 (DM2) decrease cognitive functioning in elderly people. It is uncertain if DM2 affects cognition independent of vascular disease. In patients with symptomatic arterial disease, we studied the effect of DM2 on cognition and identified clinical and radiological determinants for impaired cognition in patients with DM2. Methods: 766 patients (mean age 58.8 ± 9.5 years; 108 DM2) with symptomatic arterial disease underwent neuropsychological testing. In 542 patients (77 DM2), volumes of brain tissue, ventricles and white matter lesions were obtained by segmentation of brain MR images. Infarcts were distinguished into small (lacunar) or large (cortical or subcortical). Results: Patients with arterial disease and DM2 performed worse on neuropsychological tests compared to similar patients without DM2 (adjusted composite z-score: β - 0.14 [- 0.25 to - 0.02]). Insulin treatment, systolic and diastolic blood pressures were significantly associated with cognition in patients with DM2. Large infarcts, global and cortical atrophy on MRI were independently associated with cognition in patients with DM2. Conclusion: The presence of DM2 in patients with symptomatic arterial disease is associated with decreased cognitive functioning. Insulin treatment, high blood pressure, brain atrophy and large infarcts were determinants for cognitive dysfunction in patients with DM2 and arterial disease. © 2009 Elsevier B.V. All rights reserved.",,"Tiehuis, A. M.;Mali, W. P. T. M.;van Raamt, A. F.;Visseren, F. L. J.;Biessels, G. J.;van Zandvoort, M. J. E.;Kappelle, L. J.;van der Graaf, Y.",2009,15,,0,
815,"Objective measures of physical activity, white matter integrity and cognitive status in adults over age 80","The neuroprotective effects of physical activity (PA) are consistently shown in older adults, but the neural substrates, particularly in white matter (WM), are understudied, especially in very old adults with the fastest growth rate and the highest risk of dementia. This study quantified the association between PA and WM integrity in adults over 80. The moderating effects of cardiometabolic conditions, physical functional limitations and WM hyperintensities were also examined, as they can affect PA and brain integrity. Fractional anisotropy (FA) from normal-appearing WM via diffusion tensor imaging and WM hyperintensities were obtained in 90 participants (mean age = 87.4, 51.1% female, 55.6% white) with concurrent objective measures of steps, active energy expenditure (AEE in kcal), duration (min), and intensity (metabolic equivalents, METs) via SenseWear Armband. Clinical adjudication of cognitive status, prevalence of stroke and diabetes, systolic blood pressure, and gait speed were assessed at time of neuroimaging. Participants were on average sedentary (mean +/- SD/day: 1766 +/- 1345 steps, 202 +/- 311 kcal, 211 +/- 39 min, 1.8 +/- 1.1 METs). Higher steps, AEE and duration, but not intensity, were significantly associated with higher FA. Associations were localized in frontal and temporal areas. Moderating effects of cardiometabolic conditions, physical functional limitations, and WM hyperintensities were not significant. Neither FA nor PA was related to cognitive status. Older adults with a sedentary lifestyle and a wide range of cardiometabolic conditions and physical functional limitations, displayed higher WM integrity in relation to higher PA. Studies of very old adults to quantify the role of PA in reducing dementia burden via WM integrity are warranted.","Aged, 80 and over;Aging/ pathology/ physiology/psychology;Anisotropy;Blood Pressure;Brain/ pathology;Cognition;Diabetes Mellitus/pathology/physiopathology/psychology;Diffusion Tensor Imaging;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/pathology/physiopathology/psychology;Monitoring, Ambulatory;Motor Activity/ physiology;Sedentary Lifestyle;Stroke/pathology/physiopathology/psychology;White Matter/ pathology","Tian, Q.;Glynn, N. W.;Erickson, K. I.;Aizenstein, H. J.;Simonsick, E. M.;Yaffe, K.;Harris, T. B.;Kritchevsky, S. B.;Boudreau, R. M.;Newman, A. B.;Lopez, O. L.;Saxton, J.;Rosano, C.",2015,May 1,10.1016/j.bbr.2015.01.045,0,
816,Relationship of CT to traditional Chinese medical differentiation of syndromes and diseases in vascular dementia,"Background: It belongs to one of contents of integrated traditional and western medicine in imaging to study the relationship of CT to traditional Chinese medical differentiation of syndromes and disease for vascular dementia(VD), which is a marginal subject of intersection between modern medical imaging and traditional Chinese medicine(TCM). At present, however, the study about it is still rare. Objective: To study the relationship of CT to TCM differentiation of syndromes and diseases in order to evaluate the role of CT in TCM differentiation of syndromes and disease in VD. Design: Traverse-sectional study based on diagnosis. Setting and Participants: Thirty VD patients were recruited randomly from the Department of Neurology of PLA 252 Hospital between January 2001 and September 2002, including male 18 and female 12 with the mean age of (68.1 ± 7.8) years. Interventions: All the VD patients' TCM differentiations of syndromes and diseases and CT features were compared before clinical treatment. Main Outcome Measures: The",,"Tian, J. L.;Zhao, X. Y.",2004,Mar,,0,
817,Comparison of T2-weighted and fluid-attenuated inversion-recovery fast spin-echo MR sequences in intracerebral AIDS-associated disease,"PURPOSE: To compare the value of fast fluid-attenuated inversion-recovery (FLAIR) with T2-weighted fast spin-echo MR imaging in the detection of acquired immunodeficiency virus (AIDS)-related lesions of the brain. METHODS: Forty-four human immunodeficiency virus (HIV)-positive patients were examined with both sequences on either a 1.0-T or a 1.5-T MR system. The number, size, location, and conspicuity of the lesions were evaluated by two independent observers. Contrast ratios between lesions and normal brain/cerebrospinal fluid were determined, and contrast-to-noise ratios were calculated. RESULTS: FLAIR was found to be superior to T2-weighted fast spin-echo in detection of small lesions and of lesions located in cortical/subcortical regions and deep white matter. The two techniques were equal in delineation of lesions larger than 2 cm and for lesions located in the basal ganglia and posterior fossa. In 24 patients, more lesions were detected with the FLAIR fast spin-echo technique. Lesion/cerebrospinal fluid contrast ratios and contrast-to-noise ratios were significantly higher for the FLAIR fast spin-echo sequences than for the T2-weighted fast spin-echo sequences. CONCLUSION: FLAIR allows early detection of small lesions in subcortical and cortical locations, especially in HIV encephalitis. Because of its improved lesion detection rate and greater overall lesion conspicuity, we believe FLAIR is useful in the evaluation of subtle changes in the brains of AIDS patients with central nervous system disease, and could even replace the T2-weighted fast spin-echo technique.",AIDS Dementia Complex/ diagnosis;Adult;Brain/pathology;Female;HIV Seropositivity/ diagnosis;Humans;Image Enhancement/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Observer Variation;Sensitivity and Specificity,"Thurnher, M. M.;Thurnher, S. A.;Fleischmann, D.;Steuer, A.;Rieger, A.;Helbich, T.;Trattnig, S.;Schindler, E.;Hittmair, K.",1997,Oct,,0,
818,Highly active antiretroviral therapy for patients with AIDS dementia complex: effect on MR imaging findings and clinical course,"BACKGROUND AND PURPOSE: Recent studies have reported the clinical improvement in patients with AIDS treated with a combination of antiretroviral regimens. The purpose of our study was to describe the effects of highly active antiretroviral therapy on MR images in patients with HIV encephalopathy and to compare the clinical course with follow-up neuroimaging studies. METHODS: Initial and follow-up MR imaging findings are described in four patients with AIDS dementia complex at baseline and after antiretroviral therapy, and correlated with clinical and immunologic findings. RESULTS: Initial MR imaging revealed white matter signal abnormalities on long-TR images without mass effect and without enhancement on postcontrast images, consistent with HIV encephalopathy. Lesions were located in the basal ganglia and posterior fossa in two patients. All four patients showed progression of white matter disease on the first follow-up MR scan (mean, 6 months). On subsequent scans, regression was seen in three patients and stabilization of white matter disease was observed in one patient. Increases in CD4+ count and decreases in viral load below the limit of quantification were present in all patients. CONCLUSION: Although our patient population was small, the results suggest that disease regression in patients with AIDS dementia complex after treatment with highly active antiretroviral therapy can be characterized and monitored by MR imaging.",AIDS Dementia Complex/ drug therapy/immunology/ pathology/physiopathology;Adult;Anti-HIV Agents/ therapeutic use;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Thurnher, M. M.;Schindler, E. G.;Thurnher, S. A.;Pernerstorfer-Schon, H.;Kleibl-Popov, C.;Rieger, A.",2000,Apr,,0,
819,Diffusion-tensor MR imaging of the brain in human immunodeficiency virus-positive patients,"BACKGROUND AND PURPOSE: There is early evidence that diffusion-tensor imaging (DTI) is useful in demonstrating subtle white matter alterations in different diseases of brain. We hypothesize that DTI in several brain regions in human immunodeficiency virus-positive (HIV+) patients is useful in the early detection of HIV-related brain injury. METHODS: MR imaging and DTI were performed in 60 HIV+ patients and in 30 controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC; mm/s(2)) maps were generated and coregistered on T2-weighted images. Regions of interest were placed in the splenium and genu of the callosum, the frontal white matter, and the hippocampus. HIV+ patients were divided into those whose CD4 count were <250 cells/mm(3) or >250 cells/mm(3). According to plasma viral loads, patients were divided into those whose viral loads were <50 copies/mL, 50-100,000 copies/mL, or >100,000 copies/mL. RESULTS: Statistically significant decrease of FA was found in the genu of the corpus callosum in HIV+ patients compared with controls. FA was reduced in the frontal white matter and hippocampi in HIV+ patients compared with controls. Differences, however, were not statistically significant. No statistically significant differences were found between the HIV+ groups for FA of the splenium or between these groups and the controls. ADC values were significantly increased in the genu of HIV+ patients when compared with controls and were also increased in other locations, but without statistical significance. CONCLUSION: As used in this study, DTI was not helpful in identifying patients with early HIV infection. © American Society of Neuroradiology.",,"Thurnher, M. M.;Castillo, M.;Stadler, A.;Rieger, A.;Schmid, B.;Sundgren, P. C.",2005,2005,,0,
820,"Morphometric analysis of arteriolar tortuosity in human cerebral white matter of preterm, young, and aged subjects","Arteriolar tortuousities, consisting of vascular coils, loops, and spirals, appear in white matter in a subset of human cerebral vessels. Computerized morphometry was used to analyze brain sections from a broad age range of subjects to determine whether tortuosity is a phenomenon of aging or is associated with leukoaraiosis (LA) or Alzheimer disease (AD). Autopsy brains were studied from 55 subjects ranging in age from 23 weeks postconception to 102 years. Fourteen aged subjects were diagnosed with LA and 7 with AD. By using computerized morphometry, vascular curl (curvilinear length/straight length) was measured in white matter arterioles in 100-microm-thick, alkaline phosphatase-stained sections. Aging subjects, compared with young subjects, showed significant increases in both the prevalence and severity of tortuosity. Curl scores in aged subjects with LA or AD were not significantly different from aged controls without LA or AD. We conclude that 1) tortuous vessels are extremely rare in preterm babies, children, or young adults; 2) significant tortuosity, as indicated by elevated curl scores, begins in middle age; 3) tortuosity does not appear in a subset of aged individuals regardless of longevity; and 4) tortuosity does not appear in a subset of individuals with either LA or AD.","Adolescent;Adult;Age Factors;Aged;Aged, 80 and over;Aging/*pathology;Alzheimer Disease/pathology;Autopsy/methods;Cerebral Arteries/*pathology/ultrastructure;Cerebral Cortex/*pathology;Child;Child, Preschool;Diagnosis, Computer-Assisted/methods;Female;Humans;Infant;Leukoaraiosis/pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Postmortem Changes","Thore, C. R.;Anstrom, J. A.;Moody, D. M.;Challa, V. R.;Marion, M. C.;Brown, W. R.",2007,May,10.1097/nen.0b013e3180537147,0,
821,Association of silent lacunar infarct with brain atrophy and cognitive impairment,"OBJECTIVE: Silent lacunar infarct (SLI) is associated with cognitive decline and linked to an increased risk of stroke and dementia. We examined the association of SLI with MRI measures of cortical thickness, subcortical and lateral ventricular shapes and cognition in 285 ethnic Chinese elderly. METHODS: SLI, cortical thickness, shapes of subcortical and ventricular structures were quantified using MRI. The cognitive performance was assessed using comprehensive neuropsychological tests. Linear regression was used to examine associations among SLI, brain measures and cognition. RESULTS: SLI was associated with atrophy in multiple subcortical structures, ventricular enlargement and widespread cortical thinning. Both SLI and atrophy were independently related to poorer performance in attention, memory and language domains. Only SLI was associated with visuomotor speed and executive function, while atrophy mediated the association between SLI and visuoconstruction. CONCLUSIONS: Our findings support a vascular contribution to neurodegeneration and cognitive impairment.","Aged;Aged, 80 and over;Atrophy;Basal Ganglia/pathology;Brain/*pathology;Brain Stem/pathology;Cerebral Cortex/pathology;Dementia, Multi-Infarct/*diagnosis;Dominance, Cerebral/physiology;Female;Humans;*Image Processing, Computer-Assisted;*Imaging, Three-Dimensional;Internal Capsule/pathology;Lateral Ventricles/pathology;*Magnetic Resonance Imaging;Male;Mental Status Schedule;Mild Cognitive Impairment/*diagnosis;Neuropsychological Tests;Singapore;Stroke, Lacunar/*diagnosis;Mri;Neuroanatomy;Neuropsychology;Stroke","Thong, J. Y.;Hilal, S.;Wang, Y.;Soon, H. W.;Dong, Y.;Collinson, S. L.;Anh, T. T.;Ikram, M. K.;Wong, T. Y.;Venketasubramanian, N.;Chen, C.;Qiu, A.",2013,Nov,10.1136/jnnp-2013-305310,0,
822,Local texture descriptors for the assessment of differences in diffusion magnetic resonance imaging of the brain,"PURPOSE: Descriptors extracted from magnetic resonance imaging (MRI) of the brain can be employed to locate and characterize a wide range of pathologies. Scalar measures are typically derived within a single-voxel unit, but neighborhood-based texture measures can also be applied. In this work, we propose a new set of descriptors to compute local texture characteristics from scalar measures of diffusion tensor imaging (DTI), such as mean and radial diffusivity, and fractional anisotropy. METHODS: We employ weighted rotational invariant local operators, namely standard deviation, inter-quartile range, coefficient of variation, quartile coefficient of variation and skewness. Sensitivity and specificity of those texture descriptors were analyzed with tract-based spatial statistics of the white matter on a diffusion MRI group study of elderly healthy controls, patients with mild cognitive impairment (MCI), and mild or moderate Alzheimer's disease (AD). In addition, robustness against noise has been assessed with a realistic diffusion-weighted imaging phantom and the contamination of the local neighborhood with gray matter has been measured. RESULTS: The new texture operators showed an increased ability for finding formerly undetected differences between groups compared to conventional DTI methods. In particular, the coefficient of variation, quartile coefficient of variation, standard deviation and inter-quartile range of the mean and radial diffusivity detected significant differences even between previously not significantly discernible groups, such as MCI versus moderate AD and mild versus moderate AD. The analysis provided evidence of low contamination of the local neighborhood with gray matter and high robustness against noise. CONCLUSIONS: The local operators applied here enhance the identification and localization of areas of the brain where cognitive impairment takes place and thus indicate them as promising extensions in diffusion MRI group studies.",Alzheimer's disease;Diffusion tensor imaging;Local texture;White matter,"Thomsen, F. S.;Delrieux, C. A.;de Luis-Garcia, R.",2017,Mar,,0,
823,"Diffusion imaging, white matter, and psychopathology","The functional significance of the brain's white matter was not fully appreciated until new imaging methods were developed to visualize fiber pathways and connections in the living brain. Rapid advances in diffusion tensor imaging (DTI) have led to substantial insights into human brain development and disease processes and have thrust white matter into the focus of researchers and clinicians alike. The full clinical potential of this relatively new technique remains to be determined, but early indicators suggest that DTI will be a significant new technology in mapping mechanisms of human health and disease. Here we review brain changes that have been studied with DTI over the human lifespan and findings in a variety of neuropsychiatric disorders. We also suggest future areas where DTI is likely to have significant impact. Copyright © 2011 by Annual Reviews. All rights reserved.",,"Thomason, M. E.;Thompson, P. M.",2011,27,,0,
824,[Loss of motivation and frontal dysfunction. Role of the white matter change] Demotivation et dysfonctionnements frontaux chez le sujet age: place de la leucoaraiose,"Since the recognition of white matter changes on computed tomography, researches were done to investigate a possible relation with ageing and cognition. This study examined whether computed tomography evidence of cerebrovascular disease in the form of white matter changes was associated with decreased implicit performance of frontal tests and with a loss of motivation in a group of 10 elderly volunteers with a mild cognitive impairment and in a group of 29 demented patients; 39 old patients (28 females: 82.4 +/- 7.1; 10 males: 75.5 +/- 11.3) cared in a psycho-geriatric day care hospital were enrolled for this essay. Motivation was evaluated with a specific scale: EAD. Patients were tested during the same period with MMSE for cognition, Cornell's scale for depression, Marin's scale for apathy. There were also assessed with a battery of frontal tests: BREF test. A brain scan was used to determinate the presence of leukoaraiosis. Table 1 give a description of the population according to the pathology. Cognitive disorder, but also apathy and loss motivation, frontal evaluation significantly differ in the two studied groups. The presence of a leukoaraiosis is associated with older people, a weaker cognitive status, a more important apathy or loss of motivation, and weaker results with frontal evaluation (table 2). Similar results were obtained considering only the frontal lesions (table 3). Age related changes of the white matter observed on computed tomography were associated with a decreased cognitive status. Leukoaraiosis is associated with loss of motivation and related with a poor results on frontal assessment. Loss of motivation is associated with certain frontal dysfunctions and with brain abnormal scan anomalies.","Aged;Aging/physiology;Alzheimer Disease/diagnosis/ diagnostic imaging/ pathology;Atrophy/pathology;Basal Ganglia/pathology;Brain Diseases/ pathology/ physiopathology;Cognition Disorders/diagnosis;Female;Frontal Lobe/ pathology;Functional Laterality;Humans;Male;Motivation;Neuropsychological Tests;Occipital Lobe/pathology;Parietal Lobe/pathology;Severity of Illness Index;Tomography, X-Ray Computed","Thomas, P.;Hazif-Thomas, C.;Saccardy, F.;Vandermarq, P.",2004,Jan-Feb,,0,
825,[Loss of motivation and frontal dysfunction. Role of the white matter change],"Since the recognition of white matter changes on computed tomography, researches were done to investigate a possible relation with ageing and cognition. This study examined whether computed tomography evidence of cerebrovascular disease in the form of white matter changes was associated with decreased implicit performance of frontal tests and with a loss of motivation in a group of 10 elderly volunteers with a mild cognitive impairment and in a group of 29 demented patients; 39 old patients (28 females: 82.4 +/- 7.1; 10 males: 75.5 +/- 11.3) cared in a psycho-geriatric day care hospital were enrolled for this essay. Motivation was evaluated with a specific scale: EAD. Patients were tested during the same period with MMSE for cognition, Cornell's scale for depression, Marin's scale for apathy. There were also assessed with a battery of frontal tests: BREF test. A brain scan was used to determinate the presence of leukoaraiosis. Table 1 give a description of the population according to the pathology. Cognitive disorder, but also apathy and loss motivation, frontal evaluation significantly differ in the two studied groups. The presence of a leukoaraiosis is associated with older people, a weaker cognitive status, a more important apathy or loss of motivation, and weaker results with frontal evaluation (table 2). Similar results were obtained considering only the frontal lesions (table 3). Age related changes of the white matter observed on computed tomography were associated with a decreased cognitive status. Leukoaraiosis is associated with loss of motivation and related with a poor results on frontal assessment. Loss of motivation is associated with certain frontal dysfunctions and with brain abnormal scan anomalies.","Aged;Aging/physiology;Alzheimer Disease/diagnosis/*pathology/*radiography;Atrophy/pathology;Basal Ganglia/pathology;Brain Diseases/*pathology/*physiopathology;Cognition Disorders/diagnosis;Female;Frontal Lobe/*pathology;Functional Laterality;Humans;Male;*Motivation;Neuropsychological Tests;Occipital Lobe/pathology;Parietal Lobe/pathology;Severity of Illness Index;Tomography, X-Ray Computed","Thomas, P.;Hazif-Thomas, C.;Saccardy, F.;Vandermarq, P.",2004,Jan-Feb,,0,
826,CADASIL: Presenting as a mood disorder,"CADASIL is an autosomal dominant non-atherosclerotic vasculopathy that frequently presents as recurrent subcortical strokes, or vascular dementia in middle age. Some patients may have prominent mental symptoms or migraine. Widespread white matter demyelination and subcortical lacunar infarcts are demonstrated by magnetic resonance imaging. Demonstration of granular osmophilic material in arteries in skin biopsies is a useful diagnostic tool. CADASIL has been linked to mutation in the Notch 3 gene locus on chromosome 19. Genetic testing is available for clinical diagnosis.",,"Thomas, N.;Mathews, T.;Loganathan, A.",2002,2002,,0,
827,Treating dementia patients with vascular lesions with donepezil: A preliminary analysis,"Sixteen patients with Alzheimer's disease (AD) and 15 patients with vascular dementia (VaD) associated with subcortical white matter lesions or subcortical cardiovascular accidents (CVAs) were treated with donepezilfor 16 weeks. Within-group analyses for the AD group revealed significant improvement on some tests of working memory, and marginal improvement on the Mini-Mental State Examination and on tests of immediate free recall from a serial list-learning task. Identical analyses for the VaD group revealed substantial gains on tests of working memory and delayed recognition memory. These data suggest that medication such as donepezil may act to improve the working memory deficits known to be associated with dementia patients with subcortical vascular lesions. The clinical implications of these findings are discussed. Copyright 2005 by Lawrence Erlbaum Associates, Inc.",cholinergic receptor stimulating agent;donepezil;aged;Alzheimer disease;amnesia;article;brain cortex;cerebrovascular accident;clinical article;computer assisted tomography;controlled study;daily life activity;demography;disease severity;dose response;female;general condition improvement;Geriatric Depression Scale;human;male;mental test;multiinfarct dementia;nuclear magnetic resonance imaging;recall;recognition;scoring system;statistical analysis;treatment outcome;vascular lesion;word recognition;working memory,"Thomas, D. A.;Libon, D. J.;Ledakis, G. E.",2005,,,0,
828,The importance of appropriate partial volume correction for PET quantification in Alzheimer's disease,"PURPOSE: Alzheimer's disease (AD) is the most common form of dementia. Clinically, it is characterized by progressive cognitive and functional impairment with structural hallmarks of cortical atrophy and ventricular expansion. Amyloid plaque aggregation is also known to occur in AD subjects. In-vivo imaging of amyloid plaques is now possible with positron emission tomography (PET) radioligands. PET imaging suffers from a degrading phenomenon known as the partial volume effect (PVE). The quantitative accuracy of PET images is reduced by PVEs primarily due to the limited spatial resolution of the scanner. The degree of PVE is influenced by structure size, with smaller structures tending to suffer from more severe PVEs such as atrophied grey matter regions. The aims of this paper were to investigate the effect of partial volume correction (PVC) on the quantification of amyloid PET and to highlight the importance of selecting an appropriate PVC technique. METHODS: An improved PVC technique, region-based voxel-wise (RBV) correction, was compared against existing Van-Cittert (VC) and Muller-Gartner (MG) methods using amyloid PET imaging data. Digital phantom data were produced using segmented MRI scans from a control subject and an AD subject. Typical tracer distributions were generated for each of the phantom anatomies. Also examined were 70 clinical PET scans acquired using [(18)F]flutemetamol. Volume of interest (VOI) analysis was performed for corrected and uncorrected images. RESULTS: PVC was shown to improve the quantitative accuracy of regional analysis performed on amyloid PET images. Of the corrections applied, VC deconvolution demonstrated the worst recovery of grey matter values. MG PVC was shown to induce biases in some grey matter regions due to grey matter variability. In addition, white matter variability was shown to influence the accuracy of MG PVC in cortical grey matter and also cerebellar grey matter, a typical reference region for amyloid PET normalization in sporadic AD. RBV was shown to be more accurate than MG in terms of grey matter and white matter uptake. An increase in within-group variability after PVC was observed and is believed to be a genuine, more accurate representation of the data rather than a correction-induced error. The standardized uptake value ratio (SUVR) threshold for classifying subjects as either amyloid-positive or amyloid-negative was found to be 1.64 in the uncorrected dataset, rising to 2.25 after PVC. CONCLUSION: Care should be taken when applying PVC to amyloid PET images. Assumptions made in existing PVC strategies can induce biases that could lead to erroneous inferences about uptake in certain regions. The proposed RBV PVC technique accounts for within-compartment variability, with the potential to reduce errors of this kind.","Adult;Aged;Algorithms;Alzheimer Disease/ radionuclide imaging;Brain/radionuclide imaging;Clinical Trials as Topic;Humans;Phantoms, Imaging;Positron-Emission Tomography/ methods","Thomas, B. A.;Erlandsson, K.;Modat, M.;Thurfjell, L.;Vandenberghe, R.;Ourselin, S.;Hutton, B. F.",2011,Jun,10.1007/s00259-011-1745-9,0,
829,The fornix in health and disease: An imaging review,"The fornix is a discrete white matter tract bundle that is critical for normal cognitive functioning. Although clearly visualized at magnetic resonance imaging, its involvement in pathologic processes is often overlooked. Certain disease processes show a predilection for involvement of the fornix; in other pathologic conditions, its involvement is a rare but recognized finding. As part of the Papez circuit, it is critical in formation of memory, with damage or disease resulting in anterograde amnesia. Many different pathologic conditions can affect the fornix. Midline tumors such as gliomas or lymphoma can infiltrate it. As part of the limbic system, it may be affected by herpes simplex encephalitis. Involvement by inflammatory conditions such as multiple sclerosis may illustrate its importance in global cognitive function. An appreciation of forniceal atrophy may aid in assessment of mesial temporal sclerosis. Metabolic conditions such as Wernicke encephalopathy have been reported to involve it. The original discoveries of its role in memory arose from surgical trauma, but as a midline structure, it is susceptible to the shearing forces of diffuse axonal injury. Infarction of the fornix is rare but can result in acute amnesic syndromes. Its role in degenerative conditions such as Alzheimer disease and psychiatric conditions such as schizophrenia is a topic of research interest. Recognition of involvement of the fornix by various pathologic processes may aid in explaining the troubling clinical symptoms of amnesia. © RSNA, 2011.",,"Thomas, A. G.;Koumellis, P.;Dineen, R. A.",2011,July-August,,0,
830,Apolipoprotein E polymorphism and brain morphology in mild cognitive impairment,"Background: The apolipoprotein E (ApoE) genotype has been confirmed as the major genetic risk factor for late-onset Alzheimer's disease (AD). How the ApoE genotype and brain morphology relate to each other is only partly understood, particularly in mild cognitive impairment, the assumed prestage of AD. Methods: A total of 83 subjects with mild cognitive impairment (aging-associated cognitive decline criteria) were investigated with optimized voxel-based morphometry (VBM). We tested for differences in gray and white matter densities between groups according to their ApoE status, i.e. ε4 allele noncarriers (n = 42), subjects with one ε4 allele (n = 27) and subjects with two ε4 alleles (n = 14). Results: In individuals carrying two ε4 alleles, VBM revealed a decline in gray matter density predominantly in the medial temporal lobe region. Subjects with a single copy of the ε4 allele exhibited gray matter atrophy in the right inferior frontal gyrus. With respect to white matter changes, atrophy was only found in subjects homozygous for ε4 and confined to the right superior and middle temporal gyrus. Conclusion: Our findings support the hypothesis that the ApoE genotype in mild cognitive impairment might be associated with structural changes typically found in the early stages of AD. Copyright © 2008 S. Karger AG.",apolipoprotein E;apolipoprotein E4;aged;allele;article;brain atrophy;brain region;cognitive defect;controlled study;density gradient;DNA polymorphism;female;frontal cortex;genotype;gray matter;heterozygote;homozygosity;human;major clinical study;male;priority journal;temporal lobe;white matter,"Thomann, P. A.;Roth, A. S.;Dos Santos, V.;Toro, P.;Essig, M.;Schröder, J.",2008,,,0,
831,Diffusion tensor imaging and voxel based morphometry study in amyotrophic lateral sclerosis: Relationships with motor disability,"The aim of this study was to investigate the extent of cortical and subcortical lesions in amyotrophic lateral sclerosis (ALS) using, in combination, voxel based diffusion tensor imaging (DTI) and voxel based morphometry (VBM). We included 15 patients with definite or probable ALS and 25 healthy volunteers. Patients were assessed using the revised ALS Functional Rating Scale (ALSFRS-R). In patients, reduced fractional anisotropy was found in bilateral corticospinal tracts, the left insula/ventrolateral premotor cortex, the right parietal cortex and the thalamus, which correlated with the ALSFRS-R. Increased mean diffusivity (MD) was found bilaterally in the motor cortex, the ventrolateral premotor cortex/insula, the hippocampal formations and the right superior temporal gyrus, which did not correlate with the ALSFRS-R. VBM analysis showed no changes in white matter but widespread volume decreases in grey matter in several regions exhibiting MD abnormalities. In ALS patients, our results show that subcortical lesions extend beyond the corticospinal tract and are clinically relevant.",,"Thivard, L.;Pradat, P. F.;Lehéricy, S.;Lacomblez, L.;Dormont, D.;Chiras, J.;Benali, H.;Meininger, V.",2007,August,,0,
832,Changes in mild cognitive impairment and its subtypes as seen on diffusion tensor imaging,"BACKGROUND: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohort. METHODS: A community-based sample of 396 individuals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing. RESULTS: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI. CONCLUSIONS: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.","Aged;Aged, 80 and over;Brain/pathology;Corpus Callosum/pathology;Diffusion Tensor Imaging;Female;Frontal Lobe/pathology;Gyrus Cinguli/pathology;Humans;Logistic Models;Male;Mild Cognitive Impairment/classification/ diagnosis/pathology;Neuroimaging;Neuropsychological Tests","Thillainadesan, S.;Wen, W.;Zhuang, L.;Crawford, J.;Kochan, N.;Reppermund, S.;Slavin, M.;Trollor, J.;Brodaty, H.;Sachdev, P.",2012,Sep,10.1017/s1041610212000270,0,
833,Family History in Young Patients with Stroke,"Background and Purpose-Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. Methods-We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. Results-A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). Conclusions-Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage.",,"Thijs, V.;Grittner, U.;Dichgans, M.;Enzinger, C.;Fazekas, F.;Giese, A. K.;Kessler, C.;Kolodny, E.;Kropp, P.;Martus, P.;Norrving, B.;Ringelstein, E. B.;Rothwell, P. M.;Schmidt, R.;Tanislav, C.;Tatlisumak, T.;Von Sarnowski, B.;Rolfs, A.",2015,4,,0,
834,Cerebral microbleeds: Important or not important?,"Microbleeds are under intense scrutiny as predictors of intracerebral haemorrhage and as an in-vivo marker of cerebral amyloid angiopathy, a disease that is notoriously difficult to diagnose in a noninvasive way. Microbleeds are common in patients with haemorrhagic and ischaemic cerebrovascular disease. Cortical microbleeds are associated with cerebral amyloid angiopathy and microbleeds in deep cerebral structures and brainstem are thought to be one facet of cerebral small vessel disease. On magnetic resonance imaging a few diseases and artefacts may mimic microbleeds. In the current state of knowledge, the presence of a few microbleeds should probably not be considered a contraindication to thrombolysis or oral anticoagulation.",,"Thijs, V.",2011,2011,,0,
835,Histochemical visualization and diffusion MRI at 7 Tesla in the TgCRND8 transgenic model of Alzheimer's disease,"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been characterized by gross cortical atrophy, cellular neurodegeneration, reactive gliosis, and the presence of microscopic extracellular amyloid plaques and intracellular neurofibrillary tangles. Earlier diagnoses of AD would be in the best interest of managing the patient and would allow for earlier therapeutic intervention. By measuring the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI), a type of magnetic resonance imaging (MRI), one can quantify alterations in water diffusivity resulting from microscopic structural changes in the cell at early stages that are associated with pathophysiological processes of brain injury and/or disease progression. Whether or not this methodology is useful for AD is a question under examination. For example, DWI in suspected AD patients has shown increases in mean ADC values in the hippocampus and diminished diffusion anisotropy in the posterior white matter. However, in some cases, hippocampal ADC values appear not to change in AD patients. Moreover, to our knowledge, all DWI studies in suspected AD patients to date are technically incomplete in experimental design, because corresponding histological sections demonstrating actual plaque deposition are lacking and so it is not clear that ADC changes actually correspond to plaque deposition. In our study, we used DWI in the TgCRND8 transgenic model of Alzheimer's disease in conjunction with histological techniques and found robust plaque deposition in the transgenic strain in older animals (12-16 months old). However, we did not find statistically significant changes (p > 0.05) in ADC values (although ADC values in TgCRND8 mice did decrease in all regions examined) in mice 12-16 months old. Collectively, recent results from human studies and in rodent AD transgenic models support our findings and suggest that amyloid beta plaque load is not likely the major or primary component contributing to diffusional changes, if they occur.","Alzheimer Disease/genetics/ metabolism/pathology;Amyloid beta-Peptides/genetics/ metabolism;Animals;Brain/ metabolism/pathology;Diffusion Magnetic Resonance Imaging/ methods;Disease Models, Animal;Female;Male;Mice;Mice, Transgenic;Plaque, Amyloid/genetics/ metabolism/pathology","Thiessen, J. D.;Glazner, K. A.;Nafez, S.;Schellenberg, A. E.;Buist, R.;Martin, M.;Albensi, B. C.",2010,Jul,10.1007/s00429-010-0271-z,0,
836,Diagnostic accuracy of whole-brain computed tomographic perfusion imaging in small-volume infarctions,"PURPOSE: The aims of this study were to determine the diagnostic accuracy of whole-brain computed tomographic perfusion (WB-CTP) in small ischemic brain infarctions and to identify factors influencing the detection rate. MATERIALS AND METHODS: Out of a retrospective cohort of 1380 subjects who underwent initial WB-CTP because of suspected stroke, we selected all patients with a supratentorial magnetic resonance imaging-confirmed ischemic infarction with a volume of 8 mL or less. Infratentorial lesions were excluded. The study was designed as a case-control study with a ratio of cases to controls with no infarction in follow-up magnetic resonance imaging of 1:3. Two blinded readers independently evaluated 4 different computed tomographic perfusion parameter data sets per subject with respect to the presence and localization of a perfusion deficit. RESULTS: A total of 113 subjects met the inclusion criteria for the patient group. Overall, WB-CTP reached a sensitivity of 43.4% and a specificity of 92.9%. Among these, cortical infarctions were detected in 31 (69%) of 49 cases, whereas subcortical infarctions were detected only in 18 (28%) of 64 cases (P < 0.05). Mean final infarction diameter (17.3 mm) and volume (1.9 mL) of infarctions detected on CTP were significantly larger than those of infarctions not detected (12.4 mm and 0.8 mL, respectively; P < 0.001). Time from symptom onset did not differ significantly between infarctions that were detected or those that were not (204 vs 189 minutes; P = 0.75). CONCLUSIONS: The detection rate of WB-CTP in small infarctions highly depends on infarction localization and final size, whereas time from symptom onset does not seem to influence diagnostic accuracy. Copyright © 2014 Lippincott Williams & Wilkins.",,"Thierfelder, K. M.;Von Baumgarten, L.;Löchelt, A. C.;Meinel, F. G.;Armbruster, M.;Beyer, S. E.;Patzig, M.;Opherk, C.;Reiser, M. F.;Sommer, W. H.",2014,April,,0,
837,Penumbra pattern assessment in acute stroke patients: Comparison of quantitative and non-quantitative methods in whole brain CT perfusion,"Background and Purpose: While penumbra assessment has become an important part of the clinical decision making for acute stroke patients, there is a lack of studies measuring the reliability and reproducibility of defined assessment techniques in the clinical setting. Our aim was to determine reliability and reproducibility of different types of three-dimensional penumbra assessment methods in stroke patients who underwent whole brain CT perfusion imaging (WB-CTP). Materials and Methods: We included 29 patients with a confirmed MCA infarction who underwent initial WB-CTP with a scan coverage of 100 mm in the z-axis. Two blinded and experienced readers assessed the flow-volume-mismatch twice and in two quantitative ways: Performing a volumetric mismatch analysis using OsiriX imaging software (MMVOL) and visual estimation of mismatch (MM (EST)). Complementarily, the semiquantitative Alberta Stroke Programme Early CT Score for CT perfusion was used to define mismatch (MM (ASPECTS)). A favorable penumbral pattern was defined by a mismatch of ≥30% in combination with a cerebral blood flow deficit of ≤90 ml and an MMASPECTS score of ≥1, respectively. Inter- and intrareader agreement was determined by Kappa-values and ICCs. Results: Overall, MM(VOL) showed considerably higher inter-/intrareader agreement (ICCs: 0.751/0.843) compared to MM(EST) (0.292/0.749). In the subgroup of large (≥50 mL) perfusion deficits, inter- and intrareader agreement of MM(VOL) was excellent (ICCs: 0.961/0.942), while MM(EST) interreader agreement was poor (0.415) and intrareader agreement was good (0.919). With respect to penumbra classification, MM(VOL) showed the highest agreement (interreader agreement: 25 agreements/4 non-agreements/κ: 0.595; intrareader agreement 27/2/0.833), followed by MM(EST) (22/7/0.471; 23/6/0.577), and MM (ASPECTS) (18/11/0.133; 21/8/0.340). Conclusion: The evaluated approach of volumetric mismatch assessment is superior to pure visual and ASPECTS penumbra pattern assessment in WB-CTP and helps to precisely judge the extent of 3-dimensional mismatch in acute stroke patients. © 2014 Thierfelder et al.",,"Thierfelder, K. M.;Von Baumgarten, L.;Baumann, A. B.;Meinel, F. G.;Helck, A. D.;Opherk, C.;Straube, A.;Reiser, M. F.;Sommer, W. H.",2014,,,0,
838,The distribution of structural neuropathology in pre-clinical Huntington's disease,"Putative neuroprotective agents in Huntington's disease may have particular application before brain pathology becomes manifest clinically. If these agents were to be tested in clinical trials, a reliable marker of the burden and rate of progression of pathological change in the pre-clinical group would be needed. The present study investigates whether the Huntington's disease genotype is associated with regional differences in brain structure, particularly differences that could not be predicted from clinical or neuropsychological assessment. A secondary aim is to seek indirect evidence of pathological progression in the form of changes in local tissue volume with age, specific to the Huntington's disease genotype. Formal motor examination, neuropsychological assessment, and T(1)-weighted cerebral MRI were performed in 34 subjects who had undergone predictive genetic testing for Huntington's disease. Clinical and cognitive testing were performed blinded to gene status. A linear discriminant analysis revealed the combination of test scores (the 'optimal clinical score') which best differentiated 18 subjects carrying the Huntington's disease gene mutation (the 'gene-positive' group). Voxel-based morphometry (VBM) was used to identify regions of significant main effect of Huntington's disease gene status on grey and white matter volume and regions of significant interaction of gene status with age. In the gene-positive group, there was significant reduction in grey matter volume in the left striatum, bilateral insula, dorsal midbrain and bilateral intra-parietal sulcus relative to 'gene-negative' controls. There was a significant reduction of periventricular white matter volume with age bilaterally in the gene-positive relative to the gene-negative group. Changes remained significant when controlled for differences in optimal clinical score between subjects. This study provides evidence of distributed grey matter pathology and progressive white matter atrophy with age before clinical onset of Huntington's disease. This suggests that VBM may be useful in monitoring cross-sectional and longitudinal changes in brain structure in pre-clinical Huntington's disease and for determining the efficacy of neuroprotective agents.","Adult;Age of Onset;Brain/*pathology/physiology;Female;Functional Laterality;Genomic Imprinting;Humans;Huntington Disease/genetics/*pathology/physiopathology;Middle Aged;Parents;Pattern Recognition, Visual/physiology;Reference Values;*Trinucleotide Repeats","Thieben, M. J.;Duggins, A. J.;Good, C. D.;Gomes, L.;Mahant, N.;Richards, F.;McCusker, E.;Frackowiak, R. S.",2002,Aug,,0,
839,The human hippocampus at 7 T--in vivo MRI,"The human hippocampus plays a central role in various neuropsychiatric disorders, such as temporal lobe epilepsy (TLE), Alzheimer's dementia, mild cognitive impairment, and schizophrenia. Its volume, morphology, inner structure, and function are of scientific and clinical interest. Magnetic resonance (MR) imaging is a widely employed tool in neuroradiological workup regarding changes in brain anatomy, (sub-) volumes, and cerebral function including the hippocampus. Gain in intrinsic MR signal provided by higher field strength scanners and concomitant improvements in spatial resolution seem highly valuable. An examination protocol permitting complete, high-resolution imaging of the human hippocampus at 7 T was implemented. Coronal proton density, T2, T2*, and fluid-attenuated inversion recovery contrasts were acquired as well as an isotropic 3D magnetization-prepared rapid acquisition gradient-echo (500 microm isotropic voxel dimension, noninterpolated). Observance of energy deposition restrictions within acceptable scan times remained challenging in the acquisition of thin, spin-echo-based sections. At the higher resolution enabled by 7 T, demarcation of the hippocampus and some internal features including gray/white matter differentiation and depiction of the hippocampal mantle becomes much more viable when compared with 1.5 T; thus, in the future, this imaging technology might help in the diagnosis of subtle hippocampal changes.","Alzheimer Disease/pathology/physiopathology;Atrophy/pathology/physiopathology;Dementia/pathology/physiopathology;Epilepsy, Temporal Lobe/pathology/physiopathology;Hippocampus/ anatomy & histology/physiology;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Nerve Fibers, Myelinated/physiology/ultrastructure;Predictive Value of Tests","Theysohn, J. M.;Kraff, O.;Maderwald, S.;Schlamann, M. U.;de Greiff, A.;Forsting, M.;Ladd, S. C.;Ladd, M. E.;Gizewski, E. R.",2009,Jan,10.1002/hipo.20487,0,
840,7 tesla MRI of microbleeds and white matter lesions as seen in vascular dementia,"PURPOSE: To evaluate 7T MRI in the assessment of cerebrovascular alterations as seen in vascular dementia by means of detection of cerebral microbleeds (CMB) and depiction of white matter lesions (WML). 7T imaging was evaluated with respect to 1.5T. MATERIALS AND METHODS: Ten healthy volunteers and 10 patients with CMBs and/or WMLs were examined at 1.5T and 7T using gradient-echo (T2*, SWI) and turbo-spin-echo sequences (FLAIR). Comparisons of image quality, CMB and WML detection rates between sequences and field strengths were performed. RESULTS: Using high-resolution SWI at 7T 129 CMBs were detected compared to 75 at 1.5T using clinical SWI. With T2* at 7T 101 CMBs could be detected (33 CMBs at 1.5T). Lesion sizes were significantly larger for higher field strength. FLAIR images at 7T highlighted WMLs known from 1.5T with comparable extent. Gray and white matter contrast in FLAIR was slightly better at 1.5T, whereas image resolution and contrast of the WMLs to surrounding tissue was higher at 7T. CONCLUSION: By means of higher sensitivity for CMBs, 7T (SWI, T2*) might have significant impact on the early detection, diagnosis, and optimized antithrombotic therapy of cerebrovascular patients (eg, vascular dementia) in the future. Given the current state of technical development, 7T is approximately on par with 1.5T in the depiction of WMLs and their distribution, but holds the potential for future improvements.","Aged;Aged, 80 and over;Brain/ blood supply/pathology;Case-Control Studies;Dementia, Vascular/ pathology;Diagnostic Imaging/methods;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Microcirculation;Middle Aged;Sensitivity and Specificity","Theysohn, J. M.;Kraff, O.;Maderwald, S.;Barth, M.;Ladd, S. C.;Forsting, M.;Ladd, M. E.;Gizewski, E. R.",2011,Apr,10.1002/jmri.22513,0,
841,Evaluation of striatonigral connectivity using probabilistic tractography in Parkinson's disease,"The cardinal movement abnormalities of Parkinson's disease (PD), including tremor, muscle rigidity, and reduced speed and frequency of movements, are caused by degeneration of dopaminergic neurons in the substantia nigra that project to the putamen, compromising information flow through frontal-subcortical circuits. Typically, the nigrostriatal pathway is more severely affected on the side of the brain opposite (contralateral) to the side of the body that manifests initial symptoms. Several studies have suggested that PD is also associated with changes in white matter microstructural integrity. The goal of the present study was to further develop methods for measuring striatonigral connectivity differences between PD patients and age-matched controls using diffusion weighted magnetic resonance imaging (MRI). In this cross-sectional study, 40 PD patients and 44 controls underwent diffusion weighted imaging (DWI) using a 40-direction MRI sequence as well as an optimized 60-direction sequence with overlapping slices. Regions of interest (ROIs) encompassing the putamen and substantia nigra were hand drawn in the space of the 40-direction data using high-contrast structural images and then coregistered to the 60-direction data. Probabilistic tractography was performed in the native space of each dataset by seeding the putamen ROI with an ipsilateral substantia nigra classification target. The effect of disease group (PD versus control) on mean putamen-SN connection probability and streamline density were then analyzed using generalized linear models controlling for age, gender, education, as well as seed and target region characteristics. Mean putamen-SN streamline density was lower in PD on both sides of the brain and in both 40- and 60-direction data. The optimized sequence provided a greater separation between PD and control means; however, individual values overlapped between groups. The 60-direction data also yielded mean connection probability values either trending (ipsilateral) or significantly (contralateral) lower in the PD group. There were minor between-group differences in average diffusion measures within the substantia nigra ROIs that did not affect the results of the GLM analyses when included as covariates. Based on these results, we conclude that mean striatonigral structural connectivity differs between PD and control groups and that use of an optimized 60-direction DWI sequence with overlapping slices increases the sensitivity of the technique to putative disease-related differences. However, overlap in individual values between disease groups limits its use as a classifier.","ADRC, Alzheimer's Disease Research Center;AFNI, Analysis of Functional NeuroImages;Aged brain/metabolism/ pathology;BET, brain extraction tool;DWI, diffusion-weighted imaging;Diffusion tensor imaging/ methods;FA, fractional anisotropy;FLAIR, fluid attenuated inversion recovery;FOV, field of view;FSL, Oxford Centre for Functional MRI of the Brain Software Library;GE, general electric;HY, Hoehn and Yahr;Humans;ICC, interclass correlation coefficient;IRB, institutional review board;LMPD, longitudinal MRI biomarkers in Parkinson's disease study;MD, mean diffusivity;MRI, magnetic resonance imaging;PD, Parkinson's disease;PET, Positron Emission Tomography;Parkinson disease/classification/ pathology;RD, radial diffusivity;ROI, region of interest;SD, standard deviation;SN, substantia nigra;SNR, signal to noise ratio;SPECT, single photon emission tomography;SPM, Statistical Parametric Mapping software;Severity of illness index;TE, echo time;TFCE, threshold-free cluster enhancement;TI, inversion time;TR, repetition time;UPDRS, Unified Parkinson Disease Rating Scale;VA, Veterans Affairs","Theisen, F.;Leda, R.;Pozorski, V.;Oh, J. M.;Adluru, N.;Wong, R.;Okonkwo, O.;Dean, D. C., 3rd;Bendlin, B. B.;Johnson, S. C.;Alexander, A. L.;Gallagher, C. L.",2017,,,0,
842,Leukoaraiosis as a predictor for mortality and morbidity after an acute ischaemic stroke,"INTRODUCTION: Leukoaraiosis (LA) is a term that defines an abnormal appearance of the subcortical white matter of the brain on neuroimaging. This study was done to evaluate the predictive value of LA in terms of mortality, disability and cognitive decline at three months post-stroke and also to identify the risk factors that are independently associated with LA in a stroke population. METHODS: This was a prospective observational study of all patients with acute ischaemic stroke who were admitted to Hospital Universiti Kebangsaan Malaysia from June to November 2004. A single observer using the pre-defined diagnostic criteria recorded the information on demography, Barthel Index and mini-mental state examination. LA was diagnosed on brain computed tomography alone. RESULTS: 60 patients were recruited into the study. Three patients (five percent) died and LA was present in 29 patients (48 percent). There was no significant association between LA and mortality (p-value equals 0.89). The independent risk factors that were associated with LA were age (odds-ratio [OR] 4.43; 95 percent confidence interval [CI] 1.28-15.27) and hypertension (OR 14.3; 95 percent CI 1.40-147.42). There was a significant association between LA with early dementia (OR 3.53; 95 percent CI 1.19-10.49). However, LA did not significantly predict any functional disability (Barthel Index is less than 60) in the study population (p-value equals 0.45). CONCLUSION: Development of LA correlates significantly with ageing and hypertension. The presence of LA can also predict early cognitive dysfunction but is not associated with functional disability at three months post-stroke.","Adult;Aged;Aged, 80 and over;Brain/*radiography;Cognition Disorders/etiology;Dementia/etiology;Disability Evaluation;Female;Humans;Leukoaraiosis/*etiology/radiography;Male;Middle Aged;Prognosis;Risk Factors;Stroke/*complications/radiography;Tomography, X-Ray Computed","Thein, S. S.;Hamidon, B. B.;Teh, H. S.;Raymond, A. A.",2007,May,,0,
843,White-matter changes correlate with cognitive functioning in Parkinson's disease,"Diffusion tensor imaging (DTI) findings from emerging studies of cortical white-matter integrity in Parkinson's disease (PD) without dementia are inconclusive. When white-matter changes have been found, their relationship to cognitive functioning in PD has not been carefully investigated. To better characterize changes in tissue diffusivity and to understand their functional significance, the present study conducted DTI in 25 PD patients without dementia and 26 controls of similar ages. An automated tract-based DTI method was used. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analyzed. Neuropsychological measures of executive functioning (working memory, verbal fluency, cognitive flexibility, inhibitory control) and visuospatial ability were then correlated with regions of interest that showed abnormal diffusivity in the PD group. We found widespread reductions in FA and increases in MD in the PD group relative to controls. These changes were predominantly related to an increase in RD. Increased AD in the PD group was limited to specific frontal tracks of the right hemisphere, possibly signifying more significant tissue changes. Motor symptom severity did not correlate with FA. However, different measures of executive functioning and visuospatial ability correlated with FA in different segments of tracts, which contain fiber pathways to cortical regions that are thought to support specific cognitive processes. The findings suggest that abnormal tissue diffusivity may be sensitive to subtle cognitive changes in PD, some of which may be prognostic of future cognitive decline.",,"Theilmann, R. J.;Reed, J. D.;Song, D. D.;Huang, M. X.;Lee, R. R.;Litvan, I.;Harrington, D. L.",2013,,10.3389/fneur.2013.00037,0,
844,Gait disorders of multi-infarct dementia. CT and clinical correlation,"Twenty-five patients with various types of gait disorders of multi-infarct dementia (MID) were reported. The types of gait disorders consisted of lower body parkinsonism (LBP) plus ataxia (6 patients), LBP plus apraxia (5 patients), and a combination of LBP plus ataxia and apraxia (14 patients). Hypertension occurred in 23 (92%) of the 25 patients. Nevertheless, individual stroke risk factors and the locations of infarcts were not significantly different between the subgroups. Ventriculomegaly and ""leuko-araiosis"" as demonstrated by computed tomography occurred in more than 80% of patients in each subgroup. Atrophy of the superior vermis was seen in 16 (80%) of 20 patients with ataxia as compared to 2 (40%) of the 5 patients without ataxia (p < 0.005). These data suggest that LBP and apraxia of MID were probably determined by the presence of ventriculomegaly or leuko-araiosis or both, and the presence of ataxic component of gait disorder most probably indicates the presence of vermian atrophy.","Aged;Aged, 80 and over;Atrophy;Cerebellar Ataxia/radiography;Cerebellum/pathology;Cerebral Ventricles/pathology;Dementia, Multi-Infarct/*radiography;Female;Gait/*physiology;Humans;Hydrocephalus/radiography;Intracranial Arteriosclerosis/radiography;Male;Middle Aged;Neurologic Examination;Parkinson Disease, Secondary/radiography;*Tomography, X-Ray Computed","Thajeb, P.",1993,Mar,,0,
845,The Alzheimer's disease-related glucose metabolic brain pattern,"PURPOSE: [(18)F]fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile model, principal component analysis (SSM/PCA) aiming at identifying diagnostic neural networks in diseases, have been applied less frequently. We validated an Alzheimer's Disease-related (AD) glucose metabolic brain pattern using the SSM/PCA analysis and applied it prospectively in an independent confirmation cohort. METHODS: We used FDG-PET scans of 18 healthy controls and 15 AD patients (identification cohort) to identify an AD-related glucose metabolic covariance pattern. In the confirmation cohort (n=15), we investigated the ability to discriminate between probable AD and non-probable AD (possible AD, mild cognitive impairment (MCI) or subjective complaints). RESULTS: The AD-related metabolic covariance pattern was characterized by relatively decreased metabolism in the temporoparietal regions and relatively increased metabolism in the subcortical white matter, cerebellum and sensorimotor cortex. Receiver-operating characteristic (ROC) curves showed at a cut-off value of z=1.23, a sensitivity of 93% and a specificity of 94% for correct AD classification. In the confirmation cohort, subjects with clinically probable AD diagnosis showed a high expression of the AD-related pattern whereas in subjects with a non-probable AD diagnosis a low expression was found. CONCLUSION: The Alzheimer's disease-related cerebral glucose metabolic covariance pattern identified by SSM/PCA analysis was highly sensitive and specific for Alzheimer's disease. This method is expected to be helpful in the early diagnosis of Alzheimer's disease in clinical practice.",Aged;Alzheimer Disease/complications/ pathology/radionuclide imaging;Brain/ metabolism/radionuclide imaging;Brain Mapping;Cognition Disorders/diagnosis/etiology;Female;Fluorodeoxyglucose F18;Glucose/ metabolism;Humans;Male;Middle Aged;Neuropsychological Tests;Positron-Emission Tomography,"Teune, L. K.;Strijkert, F.;Renken, R. J.;Izaks, G. J.;de Vries, J. J.;Segbers, M.;Roerdink, J. B.;Dierckx, R. A.;Leenders, K. L.",2014,,,0,
846,Longitudinal structural and molecular neuroimaging in agrammatic primary progressive aphasia,"The agrammatic variant of primary progressive aphasia affects normal grammatical language production, often occurs with apraxia of speech, and is associated with left frontal abnormalities on cross-sectional neuroimaging studies. We aimed to perform a detailed assessment of longitudinal change on structural and molecular neuroimaging to provide a complete picture of neurodegeneration in these patients, and to determine how patterns of progression compare to patients with isolated apraxia of speech (primary progressive apraxia of speech). We assessed longitudinal structural MRI, diffusion tensor imaging and 18F-fluorodeoxyglucose PET in 11 agrammatic aphasia subjects, 20 primary progressive apraxia of speech subjects, and 62 age and gender-matched controls with two serial assessments. Rates of change in grey matter volume and hypometabolism, and white matter fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were assessed at the voxel-level and for numerous regions of interest. The greatest rates of grey matter atrophy in agrammatic aphasia were observed in inferior, middle, and superior frontal gyri, premotor and motor cortices, as well as medial temporal lobe, insula, basal ganglia, and brainstem compared to controls. Longitudinal decline in metabolism was observed in the same regions, with additional findings in medial and lateral parietal lobe. Diffusion tensor imaging changes were prominent bilaterally in inferior and middle frontal white matter and superior longitudinal fasciculus, as well as right inferior fronto-occipital fasciculus, superior frontal and precentral white matter. More focal patterns of degeneration of motor and premotor cortex were observed in primary progressive apraxia of speech. Agrammatic aphasia showed greater rates of grey matter atrophy, decline in metabolism, and white matter degeneration compared to primary progressive apraxia of speech in the left frontal lobe, predominantly inferior and middle frontal grey and white matter. Correlations were also assessed between rates of change on neuroimaging and rates of clinical decline. Progression of aphasia correlated with rates of degeneration in frontal and temporal regions within the language network, while progression of parkinsonism and limb apraxia correlated with degeneration of motor cortex and brainstem. These findings demonstrate that disease progression in agrammatic aphasia is associated with widespread neurodegeneration throughout regions of the language network, as well as connecting white matter tracts, but also with progression to regions outside of the language network that are responsible for the development of motor symptoms. The fact that patterns of progression differed from primary progressive apraxia of speech supports the clinical distinction of these syndromes.",fluorodeoxyglucose f 18;aged;apraxia of speech;article;brain atrophy;brain metabolism;brain size;Broca area;capsula interna;diffusion tensor imaging;disease exacerbation;external capsule;female;fractional anisotropy;gray matter;human;major clinical study;male;medial temporal lobe;middle frontal gyrus;molecular imaging;Montreal cognitive assessment;multimodal imaging;nerve degeneration;neuroimaging;occipitofrontal fasciculus;parkinsonism;positron emission tomography;premotor cortex;primary progressive aphasia;priority journal;superior frontal gyrus;superior longitudinal fasciculus;supplementary motor area;token test;uncinate fasciculus,"Tetzloff, K. A.;Duffy, J. R.;Clark, H. M.;Strand, E. A.;MacHulda, M. M.;Schwarz, C. G.;Senjem, M. L.;Reid, R. I.;Spychalla, A. J.;Tosakulwong, N.;Lowe, V. J.;Jack, C. R.;Josephs, K. A.;Whitwell, J. L.",2018,,10.1093/brain/awx293,0,
847,Evolution of the neuroimaging changes in fucosidosis type II,"We report on clinical and neuroradiological findings in two patients with fucosidosis type II; a 7-year-old Jordanian boy and a 3 1/4 -year-old Anglo-Canadian girl. This rare, autosomal recessive disorder is caused by deficiency of lysosomal α-fucosidase and is manifested clinically by progressive mental and motor deterioration, coarse facies, growth retardation, recurrent infections, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly and seizures. Cranial CT and magnetic resonance imaging showed density and signal abnormalities in the thalamus, globus pallidus and internal capsules bilaterally, as well as progressive CT density alterations in supratentorial white matter including the internal medullary laminae of the thalami and the internal capsules.",,"Terespolsky, D.;Clarke, J. T. R.;Blaser, S. I.",1996,1996,,0,
848,Comparisons of polio-araiosis and leuko-araiosis in dementias of ischemic vascular and alzheimer types,"Computed tomography scanners were utilized to quantitate, by Hounsfield unit (HU) densities, normal and abnormal cerebral gray and white matter compartments and their perfusion values, among patients with probable dementia of ischemic vascular (IVD: n= 10,72.7 +/- 9.0 years) and Alzheimer's types (DAT: n = 10, 72.7 +/- 5.8 years). Results were compared with similar measures among age-matched normal volunteers (n = 10, 71.0 +/- 8.2 years). ""Normal"" HU values for gray and white matter were previously obtained among younger normal volunteers (n = 27, 49.7 +/- 8.9). After adjusting for cerebral atrophy, IVD patients showed reduced HU and cerebral blood flow (CBF) values in white matter, but gray matter HU values were only reduced in frontotemporal cortex. In DAT, mean HU and CBF values for cortical and subcortical gray matter were severely reduced compared with age-matched normal and with IVD patients. Cognitive test performance correlated directly with volumes of hypodense cortex or ""polio-araiosis"" in DAT, but not in IVD, in which cognitive performance correlated directly with volumes of leuko-araiosis.",,"Terayama, Y.;Meyer, J. S.;Takashima, S.;Obara, K.;Weathers, S.",1993,,10.1016/s1052-3057(10)80072-2,0,
849,Patterns of cerebral hypoperfusion compared among demented and nondemented patients with stroke,"BACKGROUND AND PURPOSES: No reports are available that compare local cerebral perfusion among groups of patients suffering from multiple cerebral infarctions with and without cognitive impairments. The present study was designed to correlate changes in regional cerebral perfusion that may lead to dementia among patients with multiple cerebral infarctions by comparing measurements of local cerebral blood flow. METHODS: Local perfusion was measured using xenon-contrasted computed tomographic scanning among two groups of patients who had suffered from multiple cerebral infarctions: Group D (n = 12) were demented and had severe cognitive impairments, and group I (n = 11) were cognitively intact. Results were compared with similar measurements among neurologically and cognitively normal, age-matched volunteers (group N, n = 16). RESULTS: Mean local perfusion values were reduced among both groups with cerebral infarctions but to a more marked degree in group D (p less than 0.05). Perfusion of cerebral white matter was diffusely and severely reduced in group D (p less than 0.05) but was mildly reduced only in frontal and capsular white matter in group I (p less than 0.05). Perfusion of cerebral cortex was reduced in frontal (p less than 0.01) and temporal (p less than 0.01) regions among both groups but to a significantly greater degree in group D subjects (frontal, p less than 0.05; temporal, p less than 0.01), who also showed hypoperfusion of the occipital cortex (p less than 0.05), apparently because of underlying leukoaraiosis and cortical disconnections. Perfusion of the basal ganglia was reduced to the same degree among both groups of stroke patients (p less than 0.01). CONCLUSIONS: Leukoaraiosis with white matter hypoperfusion appears to be an important determinant for cognitive impairments among patients with multiple cerebral infarctions.","Aged;Aged, 80 and over;*Cerebrovascular Circulation;Cerebrovascular Disorders/complications/diagnosis/*physiopathology;Cognition Disorders/complications/physiopathology;Dementia/*complications;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Recurrence;Tomography, X-Ray Computed","Terayama, Y.;Meyer, J. S.;Kawamura, J.;Weathers, S.;Mortel, K. F.",1992,May,,0,
850,Hippocampal hypoperfusion underlying dementia due to chronic toluene intoxication,"To elucidate the pathophysiology underlying the dementia due to chronic intoxication of toluene, a positron emission tomography was carried out in a 24-year-old right-handed man who had been sniffing thinner which contains toluene for 6 years. In addition to the cerebellar ataxia and pyramidal signs, this patient exhibited a mental deterioration including recent memory disturbance: verbal IQ was 52, performance IQ was 52 and total score was 51 on WAIS-R. MRI revealed a mild diffuse cortical atrophy, symmetrical hyperintensity lesions in the corticospinal tracts including corona radiata posterior limb of the internal capsule and ventral part of the pons, and hypointensity lesions in the both thalami on T2-weighted images, whereas the changes in the deep white matter was relatively mild on T2-weighted images. In PET, both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were diffusely decreased bilaterally, and specifically in both hippocampi, they were reduced as low as 61% of the normal values as obtained from 12 young normal volunteers. Additionally, in the frontal cortex, CBF and CMRO(2) were 60% and 71% of the normal values, respectively. Although the dementia due to chronic toluene intoxication has been assumed to be closely related to the degree of the cerebral white matter lesions based on the MR findings, the present results suggest that the mental deterioration including recent memory disturbance seen in the early stage of chronic toluene intoxication is associated with the hypoperfusion and hypometabolism in the hippocampus and frontal limbic system.",,"Terashi, H.;Nagata, K.;Satoh, Y.;Hirata, Y.;Hatazawa, J.",1997,November,,0,
851,Increasing and persistent DWI changes in a patient with Hereditary Diffuse Leukoencephalopathy with Spheroids,"We report a case with genetically confirmed hereditary diffuse leukoencephalopathy with spheroids with distinctive MRI features. A 52-year-old woman with a family history of juvenile dementia presented with an 18-month history of progressive cognitive decline. Longitudinal magnetic resonance imaging studies of the brain revealed increasing and persistent white matter hyperintensities on diffusion-weighted images. Linear high intensity signal along axonal fibers arisen from the cerebral cortex was also shown. Finding of subcortical calcifications was noted on brain CT scan. Sequence analysis of CSF1R showed a novel missense mutation c.2467C > T (p.Ala823Val). Persistent and increasing diffusion on magnetic resonance image, presumably reflecting intramyelinic oedema in regions of neurodegeneration, is a distinctive feature observed in this case. The presence of this unique finding can be a diagnostic clue in the early stage of the disease. © 2013 Elsevier B.V. All rights reserved.",,"Terasawa, Y.;Osaki, Y.;Kawarai, T.;Sugimoto, T.;Orlacchio, A.;Abe, T.;Izumi, Y.;Kaji, R.",2013,15,,0,
852,[A neuroradiological study on the influence of cerebral atrophy and white matter lesion on cognitive function in the elderly],"We investigated the influence of brain atrophy and white matter lesions on cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/- 5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke from the outpatients in the Memory Clinic of our hospital. These subjects were divided into four groups on the basis of their MMSE score as follows: 14-20; moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24-27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among these four groups, we compared the frequency of the associated risk factors for cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart disease), and the severity of brain atrophy and cerebral white matter lesion which were visually evaluated by MRI technique. Brain atrophy and white matter lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep white matter lesion (DWML) and periventricular hyperintensity (PVH), respectively. Brain atrophy was divided into three grades (mild, moderate, severe) and white matter lesions were classified into four grades (0-3) using Fazekas's criteria. We performed statistical analysis to detect t parameters which correlate with and influence MMSE scores from among the MRI findings. The cases with dementia were all diagnosed as Alzheimer's disease. There were no significant differences among the four groups in mean age, the incidence of individual associated risk factors, the severity of cortical atrophy, or the grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of hippocampal atrophic change greater than a moderate grade increased in parallel with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild-D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases. Statistical analysis showed a significant negative correlation between the grade of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great influence of hippocampal atrophy on that score (step-wise regression analysis: r = 0.518, p < 0.005). From the above results, it was suggested that more than moderate atrophic change in the hippocampus might possibly be related with cognitive impairment and that both DWML and PVH less than the second grade had little influence on the decline of brain function.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Atrophy/psychology;Cerebral Cortex/*pathology;Cognition Disorders/*pathology;Hippocampus/*pathology;Humans;*Magnetic Resonance Imaging;Neuropsychological Tests","Terai, S.",2004,Sep,,0,
853,White matter changes and late-life depressive symptoms: longitudinal study,"BACKGROUND: Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear. AIMS: To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders. METHOD: In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year. RESULTS: Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01). CONCLUSIONS: White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.","Activities of Daily Living/psychology;Aged;Aged, 80 and over;Brain/ pathology;Cerebral Infarction/diagnosis/pathology/psychology;Cognition Disorders/diagnosis/pathology/psychology;Cohort Studies;Comorbidity;Dementia/diagnosis/pathology/psychology;Depressive Disorder/ diagnosis/pathology/psychology;Disability Evaluation;Disease Progression;Female;Geriatric Assessment;Humans;Leukoaraiosis/ diagnosis/pathology/psychology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Nerve Fibers, Myelinated/ pathology;Quality of Life/psychology","Teodorczuk, A.;O'Brien, J. T.;Firbank, M. J.;Pantoni, L.;Poggesi, A.;Erkinjuntti, T.;Wallin, A.;Wahlund, L. O.;Gouw, A.;Waldemar, G.;Schmidt, R.;Ferro, J. M.;Chabriat, H.;Bazner, H.;Inzitari, D.",2007,Sep,10.1192/bjp.bp.107.036756,0,
854,Structural and molecular myelination deficits occur prior to neuronal loss in the YAC128 and BACHD models of Huntington disease,"White matter (WM) atrophy is a significant feature of Huntington disease (HD), although its aetiology and early pathological manifestations remain poorly defined. In this study, we aimed to characterize WM-related features in the transgenic YAC128 and BACHD models of HD. Using diffusion tensor magnetic resonance imaging (DT-MRI), we demonstrate that microstructural WM abnormalities occur from an early age in YAC128 mice. Similarly, electron microscopy analysis of myelinated fibres of the corpus callosum indicated that myelin sheaths are thinner in YAC128 mice as early as 1.5 months of age, well before any neuronal loss can be detected. Transcript levels of myelin-related genes in striatal and cortical tissues were significantly lower in YAC128 mice from 2 weeks of age, and these findings were replicated in differentiated primary oligodendrocytes from YAC128 mice, suggesting a possible mechanistic explanation for the observed structural deficits. Concordant with these observations, we demonstrate reduced expression of myelin-related genes at 3 months of age and WM microstructural abnormalities using DT-MRI at 12 months of age in the BACHD rats. These findings indicate that WM deficits in HD are an early phenotype associated with cell-intrinsic effects of mutant huntingtin on myelin-related transcripts in oligodendrocytes, and raise the possibility that WM abnormalities may be an early contributing factor to the pathogenesis of HD.","0 (Nerve Tissue Proteins);Animals;Atrophy/pathology;Brain/metabolism;Corpus Callosum/metabolism;Corpus Striatum/metabolism;Diffusion Tensor Imaging/methods;Disease Models, Animal;Gene Expression;Humans;Huntington Disease/etiology/ genetics;Mice;Mice, Transgenic;Myelin Sheath/genetics/metabolism/ physiology;Neostriatum/metabolism;Nerve Tissue Proteins/genetics;Neurons/metabolism;Oligodendroglia/metabolism;Rats;White Matter/ physiopathology","Teo, R. T.;Hong, X.;Yu-Taeger, L.;Huang, Y.;Tan, L. J.;Xie, Y.;To, X. V.;Guo, L.;Rajendran, R.;Novati, A.;Calaminus, C.;Riess, O.;Hayden, M. R.;Nguyen, H. P.;Chuang, K. H.;Pouladi, M. A.",2016,Jul 1,,0,
855,"Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings","BACKGROUND: Antiphospholipid syndrome (APS) is a multisystem disorder characterized by arterial and venous thromboses, pregnancy morbidity, and various neuropsychiatric manifestations. Cognitive dysfunction in APS has been poorly recognized. We examined for the first time, to our knowledge, the presence of cognitive dysfunction in patients with APS and its association with clinical, laboratory, and cerebral magnetic resonance imaging characteristics. METHODS: Sixty patients (39 with primary APS and 21 with systemic lupus erythematosus-related APS) and 60 healthy individuals matched for age, sex, and education were examined by means of a comprehensive 3-hour battery of neuropsychological tests. Twenty-three patients had a history of central nervous system involvement. Fifty-nine of 60 patients underwent brain magnetic resonance imaging at the time of neuropsychological assessment. A disease control group not fulfilling criteria for APS (15 patients with systemic lupus erythematosus and 10 with rheumatoid arthritis) was also included. The demographic, clinical, and laboratory characteristics of patients were recorded. RESULTS: Twenty-five (42%) of the 60 patients with APS had cognitive deficits compared with 11 (18%) healthy control subjects (P = .005). No patient was diagnosed as having dementia. The most commonly involved cognitive domains were complex attention and verbal fluency. No difference was found in cognitive performance between patients with primary APS and those with systemic lupus erythematosus-related APS. No relationship was detected between cognitive dysfunction and prior central nervous system disease. We noted a significant association between cognitive dysfunction and livedo reticularis (P = .004) as well as between cognitive dysfunction and the presence of white matter lesions on the findings of brain magnetic resonance imaging (P=.01). No difference was detected in cognitive performance between the disease control group and healthy individuals (P=.86). CONCLUSIONS: Cognitive deficits may often be found among patients with APS, independent of any history of central nervous system involvement. Livedo reticularis and the presence of white matter lesions on brain magnetic resonance imaging are associated with an increased risk for cognitive dysfunction in APS.","Adult;Antiphospholipid Syndrome/ complications;Chi-Square Distribution;Cognition Disorders/blood/ diagnosis/ etiology;Cross-Sectional Studies;Enzyme-Linked Immunosorbent Assay;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Statistics, Nonparametric","Tektonidou, M. G.;Varsou, N.;Kotoulas, G.;Antoniou, A.;Moutsopoulos, H. M.",2006,Nov 13,10.1001/archinte.166.20.2278,0,
856,Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly,"Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer's disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.",,"Teixeira, C. V.;Rezende, T. J.;Weiler, M.;Nogueira, M. H.;Campos, B. M.;Pegoraro, L. F.;Vicentini, J. E.;Scriptore, G.;Cendes, F.;Balthazar, M. L.",2016,Jun,10.1007/s11357-016-9912-3,0,
857,Anatomical MRI and DTI in the diagnosis of Alzheimer's disease: a European multicenter study,"Diffusion tensor imaging (DTI) detects microstructural changes of the cerebral white matter in Alzheimer's disease (AD). The use of DTI for the diagnosis of AD in a multicenter setting has not yet been investigated. We used voxel-based analysis of fractional anisotropy, mean diffusivity, and grey matter volumes from multimodal magnetic resonance imaging data of 137 AD patients and 143 healthy elderly controls collected across 9 different scanners. We compared different univariate analysis approaches to model the effect of scanner, including a linear model across all scans with a scanner covariate, a random effects model with scanner as a random variable as well as a voxel-based meta-analysis. We found significant reduction of fractional anisotropy and significant increase of mean diffusivity in core areas of AD pathology including corpus callosum, medial and lateral temporal lobes, as well as fornix, cingulate gyrus, precuneus, and prefrontal lobe white matter. Grey matter atrophy was most pronounced in medial and lateral temporal lobe as well as parietal and prefrontal association cortex. The effects of group were spatially more restricted with random effects modeling of scanner effects compared to simple pooled analysis. All three analysis approaches yielded similar accuracy of group separation in block-wise cross-validated logistic regression. Our results suggest similar effects of center on group separation based on different analysis approaches and confirm a typical pattern of cortical and subcortical microstructural changes in AD using a large multimodal multicenter data set.","Aged;Algorithms;Alzheimer Disease/ diagnosis/pathology/psychology;Brain/pathology;Data Interpretation, Statistical;Diffusion Tensor Imaging/instrumentation/ methods;Educational Status;Europe;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/instrumentation/ methods;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies;Socioeconomic Factors","Teipel, S. J.;Wegrzyn, M.;Meindl, T.;Frisoni, G.;Bokde, A. L.;Fellgiebel, A.;Filippi, M.;Hampel, H.;Kloppel, S.;Hauenstein, K.;Ewers, M.",2012,,10.3233/jad-2012-112118,0,
858,Multivariate network analysis of fiber tract integrity in Alzheimer's disease,"Axonal and dendritic integrity is affected early in Alzheimer's disease (AD). Studies using region of interest or voxel-based analysis of diffusion tensor imaging data found significant decline of fractional anisotropy, a marker of fiber tract integrity, in selected white matter areas. We applied a multivariate network analysis based on principal component analysis to fractional anisotropy maps derived from diffusion-weighted scans from 15 AD patients, and 14 elderly healthy controls. Fractional anisotropy maps were obtained from an EPI diffusion sequence using parallel imaging to reduce distortion artifacts. We used high-dimensional image warping to control for partial volume effects due to white matter atrophy in AD. We found a significant regional pattern of fiber changes (p < 0.01) indicating that the integrity of intracortical projecting fiber tracts (including corpus callosum, cingulum and fornix, and frontal, temporal and occipital lobe white matter areas) was reduced, whereas extracortical projecting fiber tracts, including the pyramidal and extrapyramidal systems and somatosensory projections, were relatively preserved in AD. Effects of a univariate analysis were almost entirely contained within the multivariate effect. Our findings illustrate the use of a multivariate approach to fractional anisotropy data that takes advantage of the highly organized structure of anisotropy maps, and is independent of multiple comparison correction and partial volume effects. In agreement with post-mortem evidence, our study demonstrates dissociation between intracortical and extracortical projecting fiber systems in AD in the living human brain.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Imaging, Three-Dimensional/ methods;Male;Multivariate Analysis;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology","Teipel, S. J.;Stahl, R.;Dietrich, O.;Schoenberg, S. O.;Perneczky, R.;Bokde, A. L.;Reiser, M. F.;Moller, H. J.;Hampel, H.",2007,Feb 1,10.1016/j.neuroimage.2006.07.047,0,
859,Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study,"Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Anisotropy;Bias (Epidemiology);Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging/ methods;Europe;Female;Humans;Middle Aged;Nerve Fibers, Myelinated/ pathology;Phantoms, Imaging;Young Adult","Teipel, S. J.;Reuter, S.;Stieltjes, B.;Acosta-Cabronero, J.;Ernemann, U.;Fellgiebel, A.;Filippi, M.;Frisoni, G.;Hentschel, F.;Jessen, F.;Kloppel, S.;Meindl, T.;Pouwels, P. J.;Hauenstein, K. H.;Hampel, H.",2011,Dec 30,10.1016/j.pscychresns.2011.05.012,0,
860,Regional networks underlying interhemispheric connectivity: an EEG and DTI study in healthy ageing and amnestic mild cognitive impairment,"Interhemispheric coherence derived from electroencephalogram (EEG) recordings is a measure of functional interhemispheric connectivity. Diffusion tensor imaging (DTI) determines the integrity of subcortical fiber tracts. We studied the pattern of subcortical fiber tracts underlying interhemispheric coherence and its alteration in 16 subjects with amnestic mild cognitive impairment (MCI), an at risk syndrome for Alzheimer's disease, and 20 cognitively healthy elderly control subjects using resting state EEG and high resolution DTI at 3 T. We used a multivariate network approach based on principal component analysis to determine effects of coherence on the regional pattern of diffusivity. Temporo-parietal coherence in the alpha band was significantly correlated with diffusivity in predominantly posterior white matter tracts including posterior corpus callosum, parietal, temporal and occipital lobe white matter, thalamus, midbrain, pons, and cerebellum, both in MCI subjects and controls (P < 0.05). In MCI subjects, frontal coherence in the alpha band was significantly correlated with a predominately frontal pattern of diffusivity including fiber tracts of the anterior corpus callosum, frontal lobe white matter, thalamus, pons, and cerebellum (P < 0.05). The study provides a methodology to access specific networks of subcortical fiber tracts subserving the maintenance of interhemispheric resting state coherence in the human brain.","Aged;Aged, 80 and over;Aging;Amnesia/complications/ pathology/ physiopathology;Brain/ pathology/ physiopathology;Brain Mapping;Cognition Disorders/complications/ pathology/ physiopathology;Diffusion Magnetic Resonance Imaging;Electroencephalography;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Multivariate Analysis;Neural Pathways/pathology/physiopathology","Teipel, S. J.;Pogarell, O.;Meindl, T.;Dietrich, O.;Sydykova, D.;Hunklinger, U.;Georgii, B.;Mulert, C.;Reiser, M. F.;Moller, H. J.;Hampel, H.",2009,Jul,10.1002/hbm.20652,0,
861,Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study,"Cross-sectional studies using diffusion tensor imaging (DTI) suggest decline of the integrity of intracortically projecting fiber tracts with aging and in neurodegenerative diseases, such as Alzheimer's disease (AD). Longitudinal studies on the change of fiber tract integrity in normal and pathological aging are still rare. Here, we prospectively studied 11 healthy elderly subjects and 14 subjects with amnestic mild cognitive impairment (MCI), a clinical risk group for AD, using high-resolution DTI and MRI at baseline and after 13 to 16 months follow-up. Fractional anisotropy (FA), a DTI measure of fiber tract integrity, was compared across time points and groups using a repeated measures linear model and tract based spatial statistics. Additionally, we determined rates of grey matter and white matter atrophy using automated deformation based morphometry. Healthy elderly subjects showed decline of FA in intracortical projecting fiber tracts, such as corpus callosum, superior longitudinal fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulate bundle (p < 0.05, corrected for multiple comparisons). MCI subjects showed significant FA decline predominantly in the anterior corpus callosum (p < 0.05, corrected for multiple comparisons). Grey and white matter atrophy involved prefrontal, parietal, and temporal lobe areas in controls and prefrontal, cingulate, and parietal lobe areas in MCI subjects and agreed with the pattern of fiber tract changes. Our findings indicate that DTI allows detection of microstructural changes in subcortical fiber tracts over time that are related to aging as well as to early stages of AD type neurodegeneration. The underlying mechanisms for these changes are unknown.","Aged;Aged, 80 and over;Aging;Analysis of Variance;Anisotropy;Apolipoproteins E/genetics;Brain/ pathology;Brain Mapping;Chi-Square Distribution;Cognition Disorders/ diagnosis/genetics;Cross-Sectional Studies;Diffusion Tensor Imaging/methods;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Time Factors","Teipel, S. J.;Meindl, T.;Wagner, M.;Stieltjes, B.;Reuter, S.;Hauenstein, K. H.;Filippi, M.;Ernemann, U.;Reiser, M. F.;Hampel, H.",2010,,10.3233/jad-2010-100234,0,
862,White matter microstructure in relation to education in aging and Alzheimer's disease,"The reduced risk of dementia in high-educated individuals has been suggested to reflect brain reserve capacity. In the present study, we determined the association between integrity of white matter microstructure and education separately in twenty-one patients with clinically probable Alzheimer's disease (AD) and 18 healthy elderly subjects. We used fractional anisotropy derived from high-resolution diffusion-tensor weighted imaging at 3 Tesla as an in vivo marker of white matter microstructure. Based on multivariate network analysis, more years of education were associated with reduced white matter integrity of medial temporal lobe areas and association fiber tracts when age, gender, and dementia severity had been controlled for (p < 0.001). In controls, higher education was associated with greater white matter integrity in medial temporal lobe areas and association fiber tracts (p < 0.001). In multiple regression models, education was the main factor accounting for fiber tract integrity even when occupation was taken into account. Reduced fiber tract integrity with higher education at the same level of cognitive impairment in AD patients and higher fiber tract integrity with higher education in similar white matter areas in cognitively healthy controls agrees with the hypothesis that white matter microstructure may contribute to brain reserve capacity in humans.","Age of Onset;Aged;Aged, 80 and over;Aging/ pathology/ psychology;Alzheimer Disease/ pathology/ rehabilitation;Anisotropy;Brain Mapping;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Risk Factors","Teipel, S. J.;Meindl, T.;Wagner, M.;Kohl, T.;Burger, K.;Reiser, M. F.;Herpertz, S.;Moller, H. J.;Hampel, H.",2009,,10.3233/jad-2009-1077,0,
863,Hippocampus and Basal Forebrain Volumetry for Dementia and Mild Cognitive Impairment Diagnosis: could It Be Useful in Primary Care?,"Background: Once a patient or a knowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations. Objective: To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as a proxy for cerebrovascular comorbidity on diagnostic accuracy. Methods: We determined hippocampus and BF volumes and white matter lesion load from MRI scans of 71 participants included in a primary care intervention trial (clinicaltrials.gov identifier: NCT01401582) and matched 71 participants stemming from a memory clinic. Samples included healthy controls and people with mild cognitive impairment (MCI), AD dementia, mixed dementia, and non-AD related dementias. Results: Volumetric measures reached similar effect sizes and cross-validated levels of accuracy in the primary care and the memory clinic samples for the discrimination of AD and mixed dementia cases from healthy controls. In the primary care MCI cases, volumetric measures reached only random guessing levels of accuracy. White matter lesions had only a modest effect on effect size and diagnostic accuracy. Conclusions: Hippocampus and BF volumetry may usefully be employed for the identification of AD and mixed dementia, but the detection of MCI does not benefit from the use of these volumetric markers in a primary care setting. Copyright 2017 - IOS Press and the authors. All rights reserved.",aged;Alzheimer disease di [Diagnosis];area under the curve;article;basal forebrain;basal ganglion;brain size;comorbidity;controlled clinical trial;controlled study;diagnostic accuracy;diagnostic test accuracy study;female;fusiform gyrus;gray matter;hippocampus;human;major clinical study;male;mild cognitive impairment di [Diagnosis];neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;primary medical care;priority journal;receiver operating characteristic;sensitivity and specificity;volumetry;white matter;white matter lesion;Alzheimer disease;diagnosis;effect size;hospital;intervention study;memory;mild cognitive impairment;nuclear magnetic resonance imaging;population based case control study;primary medical care,"Teipel, S. J.;Keller, F.;Thyrian, J. R.;Strohmaier, U.;Altiner, A.;Hoffmann, W.;Kilimann, I.",2017,,,0,
864,Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease,"BACKGROUND: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. OBJECTIVES: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. PATIENTS AND METHODS: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T2-weighted magnetic resonance imaging scans. RESULTS: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. CONCLUSION: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism;Atrophy;Cerebral Cortex/ metabolism/pathology;Corpus Callosum/ pathology;Female;Glucose/ metabolism;Humans;Male;Middle Aged;Tomography, Emission-Computed","Teipel, S. J.;Hampel, H.;Pietrini, P.;Alexander, G. E.;Horwitz, B.;Daley, E.;Moller, H. J.;Schapiro, M. B.;Rapoport, S. I.",1999,Apr,,0,
865,Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease,"OBJECTIVE: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects. METHODS: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load. RESULTS: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age. CONCLUSION: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Brain/*anatomy & histology/*pathology;Corpus Callosum/*anatomy & histology/*pathology;Frontal Lobe/anatomy & histology/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Middle Aged;Neurons/cytology/pathology;Reference Values;Regression Analysis","Teipel, S. J.;Hampel, H.;Alexander, G. E.;Schapiro, M. B.;Horwitz, B.;Teichberg, D.;Daley, E.;Hippius, H.;Moller, H. J.;Rapoport, S. I.",1998,Nov,,0,
866,Fractional anisotropy changes in Alzheimer's disease depend on the underlying fiber tract architecture: a multiparametric DTI study using joint independent component analysis,"Diffusion tensor imaging (DTI) allows the simultaneous measurement of several diffusion indices that provide complementary information on the substrate of white matter alterations in neurodegenerative diseases. These indices include fractional anisotropy (FA) as measure of fiber tract integrity, and the mode of anisotropy (Mode) reflecting differences in the shape of the diffusion tensor. We used a multivariate approach based on joint independent component analysis of FA and Mode in a large sample of 138 subjects with Alzheimer's disease (AD) dementia, 37 subjects with cerebrospinal fluid biomarker positive mild cognitive impairment (MCI-AD), and 153 healthy elderly controls from the European DTI Study on Dementia to comprehensively study alterations of microstructural white matter integrity in AD dementia and predementia AD. We found a parallel decrease of FA and Mode in intracortically projecting fiber tracts, and a parallel increase of FA and Mode in the corticospinal tract in AD patients compared to controls. Subjects with MCI-AD showed a similar, but spatially more restricted pattern of diffusion changes. Our findings suggest an early axonal degeneration in intracortical projecting fiber tracts in dementia and predementia stages of AD. An increase of Mode, parallel to an increase of FA, in the corticospinal tract suggests a more linear shape of diffusion due to loss of crossing fibers along relatively preserved cortico-petal and cortico-fugal fiber tracts in AD. Supporting this interpretation, we found three populations of fiber tracts, namely cortico-petal and cortico-fugal, commissural, and intrahemispherically projecting fiber tracts, in the peak area of parallel FA and Mode increase.","Aged;Alzheimer Disease/diagnosis/ pathology;Anisotropy;Axons/pathology;Brain/ pathology;Diffusion Magnetic Resonance Imaging/methods;Diffusion Tensor Imaging/methods;Disease Progression;Early Diagnosis;Europe;Female;Humans;Image Processing, Computer-Assisted/methods;Male;Mild Cognitive Impairment/diagnosis/ pathology;Nerve Degeneration/pathology;Nerve Fibers, Myelinated/ pathology;Pyramidal Tracts/pathology;White Matter/ pathology","Teipel, S. J.;Grothe, M. J.;Filippi, M.;Fellgiebel, A.;Dyrba, M.;Frisoni, G. B.;Meindl, T.;Bokde, A. L.;Hampel, H.;Kloppel, S.;Hauenstein, K.",2014,,10.3233/jad-131829,0,
867,Progression of corpus callosum atrophy in Alzheimer disease,"BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.",Aged;Alzheimer Disease/ complications;Atrophy;Biomarkers;Corpus Callosum/ pathology;Cross-Sectional Studies;Disease Progression;Female;Humans;Male;Severity of Illness Index,"Teipel, S. J.;Bayer, W.;Alexander, G. E.;Zebuhr, Y.;Teichberg, D.;Kulic, L.;Schapiro, M. B.;Moller, H. J.;Rapoport, S. I.;Hampel, H.",2002,Feb,,0,
868,Measuring Cortical Connectivity in Alzheimer's Disease as a Brain Neural Network Pathology: Toward Clinical Applications,"OBJECTIVES: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer's disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. METHODS: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). RESULTS: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior-posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. CONCLUSIONS: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138-163).",,"Teipel, S.;Grothe, M. J.;Zhou, J.;Sepulcre, J.;Dyrba, M.;Sorg, C.;Babiloni, C.",2016,Feb,10.1017/s1355617715000995,0,
869,Clinical-diffusion mismatch defined by NIHSS and ASPECTS in non-lacunar anterior circulation infarction,"Objectives: Instead of the mismatch in MRI between the perfusion-weighted imaging (PWI) lesion and the smaller diffusion-weighted imaging (DWI) lesion (PWI-DWI mismatch), clinical-DWI mismatch (CDM) has been proposed as a new diagnostic marker of brain tissue at risk of infarction in acute ischemic stroke. The Alberta Stroke Program Early CT Score (ASPECTS) has recently been applied to detect early ischemic change of acute ischemic stroke. The present study applies the CDM concept to DWI data and investigated the utility of the CDM defined by the NIH Stroke Scale (NIHSS) and ASPECTS in patients with non-lacunar anterior circulation infarction. Methods: Eighty-seven patients with first ever ischemic stroke within 24 hours of onset with symptoms of non-lacunar anterior circulation infarction with the NIHSS score ≥ 8 were enrolled. Initial lesion extent was measured by the ASPECTS on DWI within 24 hours, and initial neurological score was measured by the NIHSS. As NIHSS ≥ 8 has been suggested as a clinical indicator of a large volume of ischemic brain tissue, and the majority of patients with non-lacunar anterior infarction with score of NIHSS < 8 had lesions with ASPECTS ≥ 8 on DWI, so CDM was defined as NIHSS ≥ 8 and DWI-ASPECTS 8 ≥. We divided patients into matched and mismatched patient groups, and compared them with respect to background characteristics, neurological findings, laboratory data, radiological findings and outcome. Results: There were 35 CDM-positive patients (P group, 40.2%) and 52 CDM-negative patients (N group , 59.8%). P group patients had a higher risk of early neurological deterioration (END) than N group patients (37.1% vs 13.5%, p < 0.05), which were always accompanied by lesion growth defined by 2 or more points decrease on ASPECTS (36 to 72 hours after onset on CT). The NIHSS at entry were significantly lower in the P group, but there was no difference in the outcome at three months measured by the modified Rankin Scale. However, CDM was not an independent predictor of END by multiple logistic regression analysis. Conclusions: Patients with CDM had high rate of early neurological deterioration and lesion growth. CDM defined as NIHSS ≥ 8 and DWI-ASPECTS ≥ 8 can be another marker for detecting patients with tissue at risk of infarction, but more work is needed to clarify whether this CDM method is useful in acute stroke management. © 2007 Steinkopff Verlag.",,"Tei, H.;Uchiyama, S.;Usui, T.",2007,March,,0,
870,"Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring","Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109. years old), centenarians (CENT) (100-104. years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p. =. 0.027), angina (p. =. 0.016) and depression (p. =. 0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p. =. 0.034) and hypertension (p. =. 0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p. <. 0.001) and the shortest (p. <. 0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.",acute heart infarction;age distribution;age releted disease;aged;angina pectoris;article;cerebrovascular accident;chronic obstructive lung disease;controlled study;dementia;depression;geriatric disorder;health status;heart arrhythmia;human;hypertension;leukocyte telomere length;life expectancy;longevity;osteoarthritis;prevalence;progeny;telomere;very elderly,"Tedone, E.;Arosio, B.;Gussago, C.;Casati, M.;Ferri, E.;Ogliari, G.;Ronchetti, F.;Porta, A.;Massariello, F.;Nicolini, P.;Mari, D.",2014,,,0,
871,Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging,"BACKGROUND: Multislide proton magnetic resonance spectroscopic imaging (1H-MRSI) permits the simultaneous acquisition of N-acetylaspartate (NA), choline (Cho), creatine/phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. NA is inferred to be a neuron-specific molecule, whereas Cho mainly reflects glycerophosphocholine and phosphocholine, compounds involved in phospholipid metabolism. OBJECTIVE: To assess whether 1H-MRSI could detect a regional pattern of cortical and subcortical involvement in the brain of Alzheimer's disease (AD) patients. METHODS: 1H-MRSI was performed in 15 patients with probable AD and 15 age-matched healthy controls. Regions of interest (ROIs) were selected from frontal (FC), temporal (TC), parietal (PC), occipital, and insular cortices, subcortical white matter (WM), and thalamus. RESULTS: In AD patients, we found a significant reduction of NA/Cre in the FC, TC, and PC and a significant reduction of Cho/Cre in the WM. CONCLUSIONS: This 1H-MRSI study of AD patients shows a regional pattern of neuronal damage in the associative cortices, as revealed by significant reduction of NA/Cre in the FC, TC, and PC, and regional derangement of phospholipid metabolism, as revealed by significant reduction of Cho/Cre in the WM.",Aged;Alzheimer Disease/ metabolism/ pathology;Brain/ metabolism/ pathology;Brain Mapping;Humans;Magnetic Resonance Imaging/ methods;Middle Aged;Protons,"Tedeschi, G.;Bertolino, A.;Lundbom, N.;Bonavita, S.;Patronas, N. J.;Duyn, J. H.;Metman, L. V.;Chase, T. N.;Di Chiro, G.",1996,Sep,,0,
872,Leukoaraiosis with mild cognitive impairment,"As the ageing population continues to increase, the prevalence of age-related cognitive impairment has been on the rise. Mild cognitive impairment (MCI) is now widely recognised as the early stage of dementia. Mild cognitive impairment is closely associated with cerebral white matter lesions (WMLs), specifically in the case of leukoaraiosis (LA). A previous diffusion tensor imaging (DTI) has demonstrated that white matter changes might damage cognitive function in LA patients, and the cognitive function might decrease with the deterioration of LA. Through consulting and analysing documents, we found that both of them share similarities in risk factors, pathogenesis, pathological changes, and imaging manifestations. The main characteristics of LA patients with MCI (LACI) are the early and apparent manifestations of delayed memory, attention, impaired executive function, and close association with dementia. This analysis of LACI may contribute to an early diagnosis of LACI and provide possible treatment for LACI.",,"Te, M.;Zhao, E.;Xingyue, Z.;Qinjian, S.;Chuanqiang, Q.",2015,1,,0,
873,Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network,"PURPOSE: White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH. MATERIALS AND METHODS: Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or >/=2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation. RESULTS: VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2 = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2) = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs. CONCLUSION: In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation.",,"Tchistiakova, E.;Crane, D. E.;Mikulis, D. J.;Anderson, N. D.;Greenwood, C. E.;Black, S. E.;MacIntosh, B. J.",2015,Nov,10.1002/jmri.24917,0,
874,Migraine headache in middle age and late-life brain infarcts: Comment,,aging;brain infarction;cerebellum;dementia;disease course;headache;human;middle aged;migraine;note;nuclear magnetic resonance imaging;priority journal;seizure;white matter,"Taylor, F. R.",2010,,,0,
875,Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease,"INTRODUCTION: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. METHOD: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). RESULTS: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. CONCLUSIONS: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.","Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/ pathology/ physiopathology;Brain Mapping;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Net/diagnostic imaging/ pathology;Neuropsychological Tests;Positron-Emission Tomography;White Matter/diagnostic imaging/ pathology;Alzheimer's disease;Amyloid-beta;Fiber tract;Functional connectivity;Resting-state fMRI;Vascular;White matter hyperintensities","Taylor, A. N. W.;Kambeitz-Ilankovic, L.;Gesierich, B.;Simon-Vermot, L.;Franzmeier, N.;Araque Caballero, M. A.;Muller, S.;Hesheng, L.;Ertl-Wagner, B.;Burger, K.;Weiner, M. W.;Dichgans, M.;Duering, M.;Ewers, M.;Alzheimer's Disease Neuroimaging, Initiative",2017,Mar,,0,
876,Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease,"INTRODUCTION: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. METHOD: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). RESULTS: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. CONCLUSIONS: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.",Alzheimer's disease;Amyloid-beta;Fiber tract;Functional connectivity;Resting-state fMRI;Vascular;White matter hyperintensities,"Taylor, A. N.;Kambeitz-Ilankovic, L.;Gesierich, B.;Simon-Vermot, L.;Franzmeier, N.;Araque Caballero, M. A.;Muller, S.;Hesheng, L.;Ertl-Wagner, B.;Burger, K.;Weiner, M. W.;Dichgans, M.;Duering, M.;Ewers, M.",2016,Jul 16,10.1016/j.jalz.2016.06.2358,0,
877,Type of gradient recalled-echo sequence results in size and number change of cerebral microbleeds,,basal ganglion;brain hemorrhage;CADASIL;cerebellum;human;hypertension;letter;microangiopathy;nuclear magnetic resonance imaging;pons;thalamus;vascular amyloidosis;white matter,"Tatsumi, S.;Ayaki, T.;Shinohara, M.;Yamamoto, T.",2008,,,0,
878,Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically induced disconnection in CADASIL: an 18F-FDG PET study,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic lesions are largely confined to subcortical structures, whereas the cortex is spared. CADASIL, therefore, may serve as a model to study subcortically induced remote effects. The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection. METHODS: Eleven CADASIL patients (7 women, 4 men; mean age, 55.8 +/- 6.7 y) without cortical lesions on brain MR images underwent PET after intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according to a previously published method. For further processing, patient studies were registered to a template of a healthy control group and region-of-interest-based and voxelwise comparisons were performed. RESULTS: In CADASIL patients, mean rCMRglc was significantly reduced in all cortical and subcortical structures, compared with the values in healthy volunteers. In the subcortical gray matter, metabolic rates, given as the percentage of the mean of healthy volunteers, were 49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively. Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the frontal, parietal, temporal, and occipital lobes, respectively. On an individual level, most patients showed marked asymmetry and inhomogeneities of cortical glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed cerebellar diaschisis. CONCLUSION: This study showed that cortical glucose metabolism is significantly lower in CADASIL patients than in healthy volunteers. The observed decrease in rCMRglc may in part be explained by a reduction of cerebral blood flow and neuronal loss. In addition, our data provide evidence of remote effects secondary to the functional disruption of subcortical fiber tracts in this particular type of small-vessel disease.","Aged;Brain/metabolism/radionuclide imaging;Cerebellum/ metabolism/radionuclide imaging;Cerebral Cortex/ metabolism/radionuclide imaging;Dementia, Multi-Infarct/ metabolism/radionuclide imaging;Energy Metabolism/physiology;Female;Fluorodeoxyglucose F18/ pharmacokinetics;Glucose/ metabolism;Humans;Male;Middle Aged;Neural Pathways/metabolism/radionuclide imaging;Radiopharmaceuticals/pharmacokinetics;Tissue Distribution;Tomography, Emission-Computed/methods","Tatsch, K.;Koch, W.;Linke, R.;Poepperl, G.;Peters, N.;Holtmannspoetter, M.;Dichgans, M.",2003,Jun,,0,
879,Dementia associated with bilateral carotid occlusions: Neuropsychological and haemodynamic course after extracranial to intracranial bypass surgery,"A 55 year old man with bilateral internal carotid and unilateral vertebral artery presented subacutely with behavioural and cognitive changes featuring frontal lobe deficits. Neuropsychological testing showed severe cognitive impairment compatible with dementia. Anatomical imaging showed only a small right superior frontal infarction. Cerebral blood flow was severely reduced, with profound hypofrontality and limited hypercapnic reactivity, and cerebral metabolism was reduced primarily in the medial frontal lobes. After right sided extracranial to intracranial cerebral bypass surgery, both flow and metabolism improved, as did behavioural and neuropsychological deficits. Perfusion insufficiency from bilateral carotid occlusions, with secondarily reduced metabolism in the frontal zones bilaterally, may be an unusual cause of a reversible frontal dementia syndrome.",,"Tatemichi, T. K.;Desmond, D. W.;Prohovnik, I.;Eidelberg, D.",1995,1995,,0,
880,Confusion and memory loss from capsular genu infarction: A thalamocortical disconnection syndrome?,"We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to 'strategic-infarct dementia.'",,"Tatemichi, T. K.;Desmond, D. W.;Prohovnik, I.;Cross, D. T.;Gropen, T. I.;Mohr, J. P.;Stern, Y.",1992,1992,,0,
881,Marked reduction of anisotropy demonstrated on diffusion tensor imaging in a case of Creutzfeldt-Jakob disease,"We report findings of repeated brain diffusion tensor MR imaging (DTI) in a case of 70-year-old Creutzfeldt-Jakob disease (CJD), which have not been previously reported. The initial fractional anisotropy (FA) map of DTI was an unremarkable. However, the second study obtained 14 months later showed diffuse decrease in the FA value throughout the white matter, along with severe brain atrophy, These DTI findings suggest that CJD could involve not only the gray matter but also the white matter. We consider that the pathological processes in the white matter may include primary changes as well as those secondary to lesions in the gray matter.",,"Tateishi, H.;Fujikawa, A.;Tsuchiya, K.;Okano, H.;Itou, T.;Ohishi, C.;Sakuta, M.",2004,2004,,0,
882,A case of granulomatous angiitis of the central nervous system presented with subacute mental deterioration resembling diffuse white matter disease,"We reported a 60-year-old man with granulomatous angiitis of the central nervous system (GACNS) manifesting as subacute mental deterioration. His first symptoms were nausea and vomiting which brought him to a hospital, where no abnormality was found except for gastritis. One month later, he began to feel dizziness and brain tumor was suspected by a neurosurgeon with the MRI findings such as abnormal T2 signal and swelling in his brainstem. While he was followed up, he gradually presented mental change, disorientation and dysmnesia with the abnormal T2 signal spreading over the cerebral white matter bilaterally. Corticosteroid therapy was started based on the suspicion of a lymphoproliferative disease, and his symptoms and the abnormal MRI findings improved. Then he was referred to our department for further evaluation. Because we could not find any evidence of systemic diseases and he had been almost fully recovered, we discontinued the therapy. Soon after that, his mental deterioration as well as the abnormal T2 signal lesions on MRI relapsed. By open brain biopsy, the diagnosis of GACNS was established, and steroid pulse therapy was started. His symptoms and the abnormal T2 signal lesions improved gradually and the steroid was tapered to the maintenance dose without remission. Since the laboratory and imaging findings are not specific for the diagnosis of the angiitis confined to the central nervous system, brain biopsy is recommended for these disorders.",,"Tashiro, J.;Yokoyama, N.;Maruo, Y.;Kubota, T.;Niwa, J.;Shimoyama, N.",2001,2001,,0,
883,Clinical features of leuko-araiosis,"Objective - To study the clinical features of leuko-araiosis. Methods - Age matched groups of patients with a CT finding of pure leuko-araiosis (n = 26) and a control group with a normal CT finding (n = 26) were formed (mean ages 78.6 (SD 3.3) v 76.5 (SD 4.6) years; NS). Results - Dementia, vascular dementia, central brain atrophy on CT, disability in activities of daily living and instrumental activities of daily living, urinary incontinence, gait disorder (assistance needed), personality change, and night time confusion were found to be more commonly present in leuko-araiosis positive patients than in controls, whereas focal neurological symptoms and signs were not associated with leuko-araiosis. The occurrences of heart failure and systolic hypotension - but not hypertension - were higher in the leuko-araiosis positive group than in the controls. Leuko-araiosis was also found to be related to a less sudden onset of symptoms and a lower Hachinski score than true brain infarction(s). Conclusions - Leuko-araiosis on CT in these elderly patients seems to be a vascular disorder aetiologically different from brain infarction, with clinical manifestations of subtle onset and general disabling nature and no prominent focal neurological signs or symptoms.",aged;article;brain atrophy;brain infarction;clinical feature;computer assisted tomography;confusion;daily life activity;dementia;female;gait disorder;heart failure;human;hypertension;hypotension;leukoaraiosis;major clinical study;male;multiinfarct dementia;neurologic disease;personality disorder;priority journal;urine incontinence;vascular disease,"Tarvonen-Schröder, S.;Röyttä, M.;Räihä, I.;Kurki, T.;Rajala, T.;Sourander, L.",1996,,,0,
884,Gangliosides and sulfatide in cerebrospinal fluid in leukoaraiosis,"The aim of the study was to evaluate gangliosides and sulfatide in cerebrospinal fluid (CSF) as markers for neuronal degeneration, gliosis, and demyelination in leukoaraiosis (LA). Lumbar CSF samples were taken from 37 elderly subjects with LA on computed tomography (CT). Patients with other pathology than LA or infarction on CT were excluded. In addition, CSF samples were colleted from 16 elderly reference subjects without any neurological disease. Gangliosides GM1, GD1a, GD1b, GT1b, GD3, and sulfatide were determined. The concentration of the individual gangliosides and sulfatide showed no correlation with age. Gangliosides GD1b, GT1b, and GD3 were elevated in patients with mild LA compared to controls and patients with moderate or severe LA. GD1a was elevated in patients with mild LA compared to those with moderate LA. The concentration of sulfatide did not differ between the groups. When the patients were grouped in accordance to whether they had had cerebral infarction or not, differences between the groups were not found in the concentrations of any gangliosides and sulfatide. In conclusion, the analysis of CSF markers suggests that neuronal degeneration and gliosis predominate in the early stage of LA.",ganglioside;ganglioside GD 1a;ganglioside GD 1b;ganglioside GD3;ganglioside GM1;ganglioside GT 1b;sulfatide;aged;article;brain infarction;cerebrospinal fluid analysis;computer assisted tomography;controlled study;demyelination;female;gliosis;human;leukoaraiosis;major clinical study;male;nerve cell degeneration;priority journal,"Tarvonen-Schröder, S.",1997,,,0,
885,Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts,"Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included. © 2011 Springer-Verlag.",adult;aged;article;brain atrophy;brain size;cingulum (brain);cognitive defect;corpus callosum;executive dysfunction;executive function;female;fractional anisotropy;frontotemporal dementia;gray matter;human;major clinical study;male;neuroimaging;neuropsychology;nuclear magnetic resonance imaging;posterior cingulate;prediction;priority journal;uncinate fasciculus;white matter,"Tartaglia, M. C.;Zhang, Y.;Racine, C.;Laluz, V.;Neuhaus, J.;Chao, L.;Kramer, J.;Rosen, H.;Miller, B.;Weiner, M.",2012,,,0,
886,"Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus","Introduction: It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance. Objective: To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH. Methods: A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios. Results: A significant negative correlation of preoperative symptom duration and total tau levels (R = -0.841, P =.002) was found. There was a significant positive correlation (R = 0.648, P =.043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P =.006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = -0.657, P =.039) and the WM volume (R = -0.778, P =.023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed. Conclusion: The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study. © 2011 The Alzheimer's Association. All rights reserved.",,"Tarnaris, A.;Toma, A. K.;Pullen, E.;Chapman, M. D.;Petzold, A.;Cipolotti, L.;Kitchen, N. D.;Keir, G.;Lemieux, L.;Watkins, L. D.",2011,September,,0,
887,Cerebral white matter lesions in patients with dementia - from MCI to severe Alzheimer's disease,"BACKGROUND: Brain images of patients with Alzheimer's disease (AD) on magnetic resonance imaging (MRI) show white matter lesions (WML), which are attributed to degenerative changes of small vessels. These lesions are supposed to be among the factors supporting the diagnosis of probable AD; however their correlation with the severity of dementia requires further studies. METHODS: We examined four groups of patients with cognitive impairment: Ten patients with amnestic-MCI (Mild Cognitive Impairment), 11 with mild AD (21-24 points in MMSE), 17 with moderate AD (11-20 points in MMSE) and 15 with severe AD (3-10 points in MMSE). The T2 and FLAIR MRI sequences of the brain of each patient were assessed using the White Matter Lesions Semiquantitive Rating Scale, taking into consideration the amount, size and distribution of WML. RESULTS: WML of the brain were seen in almost all patients with AD and MCI on T2 and FLAIR sequences. The positive correlation between the patients' age and the amount and size of WML, in subcortical (T2: p<0.01, r=0.39; FLAIR: p<0.05, r=0.31) and in the periventricular region (T2: p<0.05, r=0.28; FLAIR: p<0.05, r=0.35) has been shown on both sequences. There was no correlation between the size or distribution of lesions and either hypertension or homocysteine blood level. The analysis revealed also that in both sequences, the severity of lesions in the periventricular region increased with the progression of the disease (T2: p=0.038; FLAIR: p=0.02). CONCLUSIONS: A significant factor correlating with the location of WML in patients with MCI and AD is the age of patient. The amount and size of WML in the periventricular and subcortical regions of the brain correlates with the severity of dementia. Hypertension and hyperhomocysteinemia have no influence on the presence of described lesions.","Aged;Aging;Alzheimer Disease/blood/ pathology;Brain/ pathology;Cognition Disorders/blood/ pathology;Disease Progression;Female;Homocysteine/blood;Humans;Hypertension/pathology;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology","Targosz-Gajniak, M.;Siuda, J.;Ochudlo, S.;Opala, G.",2009,Aug 15,10.1016/j.jns.2009.02.314,0,
888,Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease,"Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-beta 1-42 (Abeta) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) varepsilon4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Abeta. Individuals with a reduction in CSF Abeta levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Abeta. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Abeta. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.",APOE varepsilon4;Alzheimer's disease;amyloid-beta;cerebrospinal fluid biomarkers;fimbria;fornix;hippocampal subfields;preclinical;structural magnetic resonance imaging;tau,"Tardif, C. L.;Devenyi, G. A.;Amaral, R. S. C.;Pelleieux, S.;Poirier, J.;Rosa-Neto, P.;Breitner, J.;Chakravarty, M. M.;Group, Prevent-Ad Research",2018,Feb,,0,
889,Creutzfeldt-Jakob disease. Report of 10 neuropathologically-verified cases in Argentina,"We describe 10 neuropathologically verified patients with Creutzfeldt-Jakob disease who died in Argentina between 1980 and 1987. Two of the ten cases were Chilean by birth. Another case visited Chile several times. Two cases (one Argentinian and one Chilean) regularly consumed sheep brain. Ages ranged from 42 to 63 years and the male to female ratio was 7:3. Disease duration ranged from 3.5 to 24 months. Prodromal symptoms presented as behavioral changes in 5 patients, lasting from one year to several weeks, and as neurological impairment in the other 5. Patients developed pyramidal, extrapyramidal and cerebellar disturbances, as well as movement disorders and progressive dementia. Visual alterations were found in 5 cases and periodic EEG activity in 7. Unequivocal cortical spongiform changes, together with varying degrees of neuronal depletion and astroglial hyperplasia were constant findings. No white matter involvement was apparent either from CT brain scans or on histopathological study of biopsied and autopsied material. Increasing awareness of this disease as well as possibilities of transmission is necessary in order to provide better information on its true incidence in Argentina.",adult;article;brain cortex;case report;Creutzfeldt Jakob disease;female;human;male;middle aged;pathology;ultrastructure,"Taratuto, A. L.;Piccardo, P.;Leiguarda, R.;Granillo, R.;Monti, A.;Scarlatti, A.;Leits, A.;Morasso, C.;Marquez Vigo, C.;Vila, J.",1989,,,0,
890,MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study,"The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.","Aged;Aged, 80 and over;Analysis of Variance;Apolipoproteins E/genetics;Cognition Disorders/genetics/*pathology;Entorhinal Cortex/*pathology;Female;Follow-Up Studies;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Proportional Hazards Models","Tapiola, T.;Pennanen, C.;Tapiola, M.;Tervo, S.;Kivipelto, M.;Hanninen, T.;Pihlajamaki, M.;Laakso, M. P.;Hallikainen, M.;Hamalainen, A.;Vanhanen, M.;Helkala, E. L.;Vanninen, R.;Nissinen, A.;Rossi, R.;Frisoni, G. B.;Soininen, H.",2008,Jan,10.1016/j.neurobiolaging.2006.09.007,0,
891,Diffusion tensor studies and voxel-based morphometry of the temporal lobe to determine the cognitive prognosis in cases of Alzheimer's disease and mild cognitive impairment: Do white matter changes precede gray matter changes?,"PURPOSE: The purpose of the current study was to assess the feasibility of diffusion tensor imaging (DTI) parameters for determining the prognosis of Alzheimer's disease (AD). We also analyzed the correlation among DTI, voxel-based morphometry (VBM), and results of the mini-mental state examination (MMSE). METHODS: The subjects of this prospective study were patients with AD and mild cognitive impairment. We performed annual follow-ups with DTI, VBM, and MMSE for 2 or 3 years. On DTI, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the uncinate fascicles were measured. VBM was performed to provide a z-score for the parahippocampal gyrus. The correlations among these factors were evaluated in the same period and the next period of the follow-up study. RESULTS: For evaluation of the same period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score. Also for evaluation of the next period, both DTI parameters and z-scores showed statistically significant correlations with the MMSE score of the next period. We observed a statistically significant correlation between the ADC value of the uncinate fascicles and the z-score of the next period. CONCLUSIONS: Diffusion tensor parameters (ADC and FA) of the uncinate fascicles correlated well with cognitive function in the next year and seemed to be feasible for use as biomarkers for predicting the progression of AD. In addition, the white matter changes observed in the ADC seemed to precede changes in the gray matter volume of the parahippocampal gyrus that were represented by z-scores of VBM.",Alzheimer's disease;Biomarker;Diffusion tensor image;Prognosis;Voxel-based morphometry,"Taoka, T.;Yasuno, F.;Morikawa, M.;Inoue, M.;Kiuchi, K.;Kitamura, S.;Matsuoka, K.;Kishimoto, T.;Kichikawa, K.;Naganawa, S.",2016,,10.1186/s40064-016-2692-5,0,
892,"Diffusion anisotropy and diffusivity of white matter tracts within the temporal stem in Alzheimer disease: evaluation of the ""tract of interest"" by diffusion tensor tractography","PURPOSE: Our aim was to determine whether diffusion anisotropy and diffusivity of white matter tracts of the temporal stem in patients with Alzheimer (AD) can be evaluated independently by using diffusion tensor tractography. MATERIALS AND METHODS: Subjects included 15 patients with AD (11 women and 4 men; mean age, 74 years) and 15 age-matched control subjects (11 women and 4 men; mean age, 72 years). Diffusion tensor images were acquired by using echo-planar imaging. We drew tractographies of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop, with diffusion tensor analysis software. We measured diffusion anisotropy, diffusivity, and the number of voxels along the ""tracts of interest"" and used the Student t test to compare results between patients with AD and controls. RESULTS: Values of diffusion anisotropy of the bilateral uncinate fasciculus and left inferior occipitofrontal fasciculus were significantly lower for patients with AD than for controls. Also, values of diffusivity in the bilateral uncinate fasciculus were significantly greater for patients with AD than for controls. There was no significant difference in diffusion anisotropy or diffusivity along Meyer's loop between the 2 groups. There was no significant difference in the number of voxels included in all constructed tracts between patients with AD and controls. CONCLUSION: White matter tracts of the temporal stem can be evaluated independently by using diffusion tensor tractography, which appears to be a promising technique for determining changes in white matter in degenerative diseases.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Prospective Studies","Taoka, T.;Iwasaki, S.;Sakamoto, M.;Nakagawa, H.;Fukusumi, A.;Myochin, K.;Hirohashi, S.;Hoshida, T.;Kichikawa, K.",2006,May,,0,
893,"Relationships between white matter hyperintensities, cerebral amyloid angiopathy and dementia in a population-based sample of the oldest old","Previous reports suggest that brain white matter changes, a surrogate for small vessel disease, are related to cerebral amyloid angiopathy (CAA). However, this relationship has not been explored in population-based studies or in the oldest old (>85 years of age). We studied the relationships between white matter hyperintensities (WMH) determined by post-mortem magnetic resonance imaging (MRI) and neuropathologically assessed CAA in demented and nondemented subjects enrolled in the prospective community-based Finnish Vantaa 85+ Study. In this analysis, we evaluated scans and brain samples from 123 subjects (86% women) with a mean age of 90.6 years. We found CAA to be present in 63 % of the 123 subjects, whereas WMH was present in 74%, and dementia in 59 %. The presence of WMH of any severity did not relate to the presence or the degree of CAA severity, irrespective of the dementia status of the subjects. Furthermore, multivariate regression analysis showed a clear association between CAA and dementia but WMH was not related to dementia in this very old sample. We conclude that severe WMH may not be determined by CAA in this very elderly population.","Aged, 80 and over;Brain/ pathology;Cerebral Amyloid Angiopathy/ pathology;Community Health Planning;Dementia/ pathology;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology","Tanskanen, M.;Kalaria, R. N.;Notkola, I. L.;Makela, M.;Polvikoski, T.;Myllykangas, L.;Sulkava, R.;Kalimo, H.;Paetau, A.;Scheltens, P.;Barkhof, F.;van Straaten, E.;Erkinjuntti, T.",2013,Dec,,0,
894,How to select patients with normal pressure hydrocephalus for shunting,"The objective was to compare predictive values of clinical and CT findings, co-existing cerebrovascular disease (CVD) and CSF outflow resistance (Rcsf) for outcome of shunting in NPH. A group of 95 NPH patients was shunted and followed for one year. Gait disturbance and dementia were quantified by an NPH scale (NPHS) and handicap by the modified Rankin scale (MRS). Improvement was defined as a change of at least 15% in NPHS and one grade in MRS at last follow-up. Clinical and CT findings at entry were classified as typical or not typical for NPH. CVD was defined as a history of stroke or CT-scans showing infarcts or moderate to severe white matter hypodense lesions. Clinical and CT findings typical for NPH, absence of CVD and Rcsf > 18 mmHg/ml/min were positive tests and the reciprocal outcomes negative tests. Typical clinical and CT findings were found in 69% and 68%, CVD (history of stroke n = 14, infarcts on CT n = 13, leucoaraiosis n = 32) in 47% and Rcsf > 18 in 38% of patients. The ratio of patients classified as improved in both scales was significantly greater for those with positive than negative tests. Mean improvement differed the most between patients with and without CVD. Using logistic regression analysis Rcsf > 18 was the only significant predictor of improvement in NPHS (OR 4.4, 95% CI 1.3-16.7) and typical CT findings in MRS (OR 5.6, 95% CI 1.8-17.9). We conclude that CVD is an important predictor of poor outcome. The best strategy is to shunt NPH patients if Rcsf is > 18 mmHg/ml/min or, when Rcsf is lower, if CT findings are typical for NPH and there is no or limited CVD.","*Cerebrospinal Fluid Shunts;Cerebrovascular Disorders/complications;Dementia/complications;Humans;Hydrocephalus, Normal Pressure/etiology/*surgery;Intracranial Pressure/*physiology;Patient Selection;Regression Analysis;Treatment Outcome","Tans, J. T.;Boon, A. J.",2002,,,0,
895,Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's Disease with Verbal Memory Impairment,"OBJECTIVE: The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease. METHODS: Forty non-demented Parkinson's disease patients and forty non-Parkinson's disease controls completed two verbal memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and a story measure (Logical Memory). All participants received T1-weighted and diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge weight) were the primary imaging variables of interest with frontal lobe thickness and subcortical structure volumes as dissociating variables. RESULTS: Individuals with Parkinson's disease showed worse verbal memory, smaller entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity. For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest associations with verbal memory. A subset of Parkinson's disease patients (23%) had deficits (z-scores < -1.5) across both memory measures. Relative to non-impaired Parkinson's peers, this memory-impaired group had smaller entorhinal volumes. DISCUSSION: Although entorhinal cortex volume was significantly reduced in Parkinson's disease patients relative to non-Parkinson's peers, only white matter connections associated with the entorhinal cortex were significantly associated with verbal memory performance in our sample. There was also no suggestion of contribution from frontal-subcortical gray or frontal white matter regions. These findings argue for additional investigation into medial temporal lobe gray and white matter connectivity for understanding memory in Parkinson's disease.",,"Tanner, J. J.;Mareci, T. H.;Okun, M. S.;Bowers, D.;Libon, D. J.;Price, C. C.",2015,,10.1371/journal.pone.0133792,0,
896,Clinically relevant depressive symptoms in young stroke patients - Results of the sifap1 study,"Background: Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort. Methods: The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed. Results: From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p < 0.001). Patients with CRDS more often had arterial hypertension, diabetes mellitus, and hyperlipidemia than patients without CRDS (hypertension: 58.0 vs. 47.1%, p = 0.017; diabetes mellitus: 17.9 vs. 8.9%, p < 0.001; hyperlipidemia: 40.5 vs. 32.3%, p = 0.012). In the subgroup of patients with ischemic stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found. Conclusion: Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings.",,"Tanislav, C.;Kropp, P.;Grittner, U.;Holzhausen, M.;Fazekas, F.;Jungehülsing, G. J.;Tatlisumak, T.;Von Sarnowski, B.;Putaala, J.;Huber, R.;Thijs, V.;Schmidt, R.;Kaps, M.;Enzinger, C.;Dichgans, M.;Norrving, B.;Rolfs, A.",2015,19,,0,
897,A case of ipsilateral monoparesis by lacunar infarction: A consideration on the pathological mechanism,"An 81-year-old man had sudden-onset dysarthria and weakness in the right leg, and was admitted to our hospital in July 2009. Neurological examination showed right leg monoparesis, sensory disturbance on the right limbs, dysarthria, and decreased deep tendon reflexes. Brain MRI revealed an acute lacunar infarction in the right corona radiata and an old lacunar infarction in the left centrum semiovale, which occurred 4 years before. MR tractography disclosed impaired motor fibers in the right corona radiata, and transcranial magnetic stimulation (TMS) suggested diminished innervation from the bilateral cerebral cortices to the right leg. These results collectively indicated that reorganization of the pyramidal fibers were responsible for the monoparesis ipsilateral to the lacunar infarction, although anomalous pyramidal fibers with ipsilateral innervation were responsible for ipsilateral hemiplegia a previous study.",aged;article;brain cortex;brain infarction;brain lacunar infarction;brain region;brain ventricle;case report;corona radiata (brain);dysarthria;hemiplegia;human;innervation;ipsilateral monoparesis;limb weakness;magnetic resonance tractography;male;neurologic examination;nuclear magnetic resonance imaging;paresis;pyramidal tract;semioval center;sensory dysfunction;tendon reflex;tractography;transcranial magnetic stimulation,"Taniguchi, A.;Ii, Y.;Kawana, Y.;Asahi, M.;Naito, Y.;Shibata, M.;Maeda, M.;Tomimoto, H.",2011,,,0,
898,Cerebral vascular leak in a mouse model of amyloid neuropathology,"In Alzheimer's disease (AD), there is increasing evidence of blood-brain barrier (BBB) compromise, usually observed as 'microbleeds' correlated with amyloid plaque deposition and apoE-e{open}4 status, raising the possibility of nanotherapeutic delivery. Molecular probes have been used to study neurovascular leak, but this approach does not adequately estimate vascular permeability of nanoparticles. We therefore characterized cerebrovascular leaks in live APP+ transgenic animals using a long circulating ∼100 nm nanoparticle computed tomography (CT) contrast agent probe. Active leaks fell into four categories: (1) around the dorsomedial cerebellar artery (DMCA), (2) around other major vessels, (3) nodular leaks in the cerebral cortex, and (4) diffuse leaks. Cortical leaks were uniformly more frequent in the transgenic animals than in age-matched controls. Leaks around vessels other than the DMCA were more frequent in older transgenics compared with younger ones. All other leaks were equally prevalent across genotypes independent of age. Ten days after injection, 4 to 5 μg of the dose was estimated to be present in the brain, roughly a half of which was in locations other than the leaky choroid plexus, and associated with amyloid deposition in older animals. These results suggest that amyloid deposition and age increase delivery of nanoparticle-borne reagents to the brain, in therapeutically relevant amounts.Journal of Cerebral Blood Flow and Metabolism advance online publication, 23 July 2014; doi:10.1038/jcbfm.2014.125.",amyloid;nanoparticle;contrast medium;mouse model;neuropathology;mouse;transgenic animal;brain;blood brain barrier;computer assisted tomography;amyloid plaque;molecular probe;blood vessel permeability;metabolism;choroid plexus;artery;brain cortex;transgenics;genotype;injection;brain blood flow;Alzheimer disease,"Tanifum, E. A.;Starosolski, Z. A.;Fowler, S. W.;Jankowsky, J. L.;Annapragada, A. V.",2014,,,0,
899,Surface-based vertexwise analysis of morphometry and microstructural integrity for white matter tracts in diffusion tensor imaging: With application to the corpus callosum in Alzheimer's disease,"In this article, we present a unified statistical pipeline for analyzing the white matter (WM) tracts morphometry and microstructural integrity, both globally and locally within the same WM tract, from diffusion tensor imaging. Morphometry is quantified globally by the volumetric measurement and locally by the vertexwise surface areas. Meanwhile, microstructural integrity is quantified globally by the mean fractional anisotropy (FA) and trace values within the specific WM tract and locally by the FA and trace values defined at each vertex of its bounding surface. The proposed pipeline consists of four steps: (1) fully automated segmentation of WM tracts in a multi-contrast multi-atlas framework; (2) generation of the smooth surface representations for the WM tracts of interest; (3) common template surface generation on which the localized morphometric and microstructural statistics are defined and a variety of statistical analyses can be conducted; (4) multiple comparison correction to determine the significance of the statistical analysis results. Detailed herein, this pipeline has been applied to the corpus callosum in Alzheimer's disease (AD) with significantly decreased FA values and increased trace values, both globally and locally, being detected in patients with AD when compared to normal aging populations. A subdivision of the corpus callosum in both hemispheres revealed that the AD pathology primarily affects the body and splenium of the corpus callosum. Validation analyses and two multiple comparison correction strategies are provided. Hum Brain Mapp 38:1875-1893, 2017. (c) 2017 Wiley Periodicals, Inc.",diffusion tensor imaging;microstructural integrity;morphometry;multiple comparison correction;statistical mapping;surface map;white matter tract,"Tang, X.;Qin, Y.;Zhu, W.;Miller, M. I.",2017,Apr,,0,
900,Brainstem infarcts predict REM sleep behavior disorder in acute ischemic stroke,"BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disturbance in which patients enact their dreams while in REM sleep. The behavior is typically violent in association with violent dream content, so serious harm can be done to the patient or the bed partner. The prevalence of RBD is well-known in Parkinson's disease, Lewy body dementia, and multiple systems atrophy. However, its prevalence and causes in stroke remained unclear. The aim of this study was to determine factors influencing the appearance of RBD in a prospective cohort of patients with acute ischemic stroke. METHODS: A total of 2,024 patients with first-ever or recurrent acute ischemic stroke were admitted to the Acute Stroke Unit at the Prince of Wales Hospital between January 2010 and November 2011; 775 of them received an MRI scan. Within 2 days of admission, a research nurse collected demographic and clinical data and assessed the severity of each stroke using the National Institute of Health Stroke Scale (NIHSS). One hundred and nineteen of the 775 patients meeting study entry criteria formed the study sample. All eligible participants were invited to attend a research clinic 3 months after the onset of the index stroke. In the attendance, a research assistant administered the MMSE and the 13-item RBD questionnaire (RBDQ). RESULTS: Among 119 stroke patients, 10.9% were exhibited RBD, defined as an REM sleep behavior disorder questionnaire score of 19 or above. The proportion of patients with acute brainstem infarct was significantly higher in RBD patients than those without RBD. Compared with patients without RBD, RBD patients were more likely to have brainstem infarcts and had smaller infarct volumes. In a multivariate analysis, in which stroke location and infarct volume were inserted, brainstem infarcts were an independent predictor of RBD (odds ratio = 3.686; P = 0.032). CONCLUSIONS: The results support the notion of a predominant role of brainstem injury in the development of RBD and suggest that patients with brainstem infarcts RBD should be evaluated by a clinical neurologist.",Aged;Brain Stem Infarctions/*complications;Female;Humans;Male;REM Sleep Behavior Disorder/*epidemiology/*etiology;Stroke,"Tang, W. K.;Hermann, D. M.;Chen, Y. K.;Liang, H. J.;Liu, X. X.;Chu, W. C.;Ahuja, A. T.;Abrigo, J.;Mok, V.;Ungvari, G. S.;Wong, K. S.",2014,,10.1186/1471-2377-14-88,0,
901,Absence of cerebral microbleeds predicts reversion of vascular 'cognitive impairment no dementia' in stroke,"BACKGROUND: Cerebral microbleeds may contribute to cognitive deficits in stroke. Cognitive impairment that does not meet the criteria for dementia (cognitive impairment no dementia) is common in stroke, and patients with such impairment can revert to normal cognition. AIMS AND HYPOTHESIS: This study examined the association between cerebral microbleeds and the reversion of cognitive impairment no dementia. METHOD: A total of 328 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. All subjects were assessed for cognitive impairment no dementia with a neuropsychological test battery at three- and 15 months following the index stroke. Of the 180 patients with cognitive impairment no dementia at three-months poststroke, 143 (79 . 4%) attended the 15-month follow-up. Twenty-nine subjects had reverted from cognitive impairment no dementia to normal cognitive status (reverters), 98 were nonreverters and 16 had progressed to dementia. RESULTS: In univariate analysis, the reverters were found to be younger, less likely to have hypertension and cerebral microbleeds, and to have smaller white matter hyperintensity volumes. In multivariate analysis, the absence of cerebral microbleeds remained an independent predictor of reversion with an odds ratio of 4.3. Absence of deep cerebral microbleeds predicted the reversion of the language domain, whereas the absence of lobar cerebral microbleeds predicted the reversion of the visuomotor speed domain. CONCLUSIONS: The results suggest that the absence of cerebral microbleeds may be associated with a higher likelihood of a reversible cognitive impairment in stroke patients. The mechanism of how this occurs is not well understood.","Aged;Asian Continental Ancestry Group;Attention/physiology;Cerebral Hemorrhage/*complications/*diagnosis;Cerebral Infarction/epidemiology/pathology;Dementia/diagnosis/psychology;Diagnostic and Statistical Manual of Mental Disorders;Diffusion Magnetic Resonance Imaging;Executive Function;Female;Follow-Up Studies;Hemosiderin/metabolism;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Logistic Models;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Mild Cognitive Impairment/*diagnosis/*etiology/psychology;Neurologic Examination;Neuropsychological Tests;Predictive Value of Tests;Psychomotor Performance/physiology;Socioeconomic Factors;Stroke/*complications/*psychology;Survivors;Visual Perception/physiology","Tang, W. K.;Chen, Y. K.;Lu, J. Y.;Wong, A.;Mok, V.;Chu, W. C.;Ungvari, G. S.;Wong, K. S.",2011,Dec,10.1111/j.1747-4949.2011.00682.x,0,
902,Cerebral microbleeds and symptom severity of post-stroke depression: A magnetic resonance imaging study,"Background: Cerebral microbleeds (CMBs) are common in stroke survivors, although their clinical significance in the development of psychiatric conditions following stroke remains unknown. This study examines the association between post-stroke depression (PSD) symptom severity and CMBs. Methods: Amongst the 4088 patients with acute ischemic stroke who had been admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong, between December 2004 and May 2009, 994 patients were recruited. A psychiatrist administered the Structural Clinical Interview for DSM-IV to all 994 patients and made a diagnosis of PSD three months after the index stroke. PSD symptom severity was assessed with the 15-item Geriatric Depression Scale (GDS). Seventy-eight patients were found to have PSD. The presence and location of CMBs were evaluated with magnetic resonance imaging (MRI). Results: Seventy-eight patients (7.8%) had PSD. CMBs were identified in 20 PSD patients. Relative to the no-CMB group, the mean GDS score of patients with lobar CMBs was significantly higher (12.6 ± 2.6 versus 10.4 ± 2.5, p = 0.01 after adjusting for age, sex, global cognitive functions, neurological deficits and white matter hyperintensities). Limitations: Patients with more severe stroke, those who died before the three-month follow-up and those who became depressed later were excluded, as were those unable to give their consent due to dementia or aphasia. These selection biases may limit the generalizability of the findings. Conclusions: The results suggest that lobar CMBs may contribute to PSD symptom severity. The importance of CMBs in the pathogenesis of other psychiatric disorders in stroke survivors and other patient populations warrants further investigation. © 2010 Elsevier B.V. All rights reserved.",,"Tang, W. K.;Chen, Y. K.;Lu, J. Y.;Chu, W. C. W.;Mok, V. C. T.;Ungvari, G. S.;Wong, K. S.",2011,March,,0,
903,Frequency and Determinants of Poststroke Dementia in Chinese,"Background and Purpose-Both dementia and stroke are major health problems in Chinese societies. Stroke is a frequent cause of dementia. Only a few studies have been published on poststroke dementia (PSDE), none of which has investigated a consecutive stroke cohort in Asian patient populations. The objective of this study was to examine the prevalence and clinical correlates of PSDE in Chinese stroke patients in Hong Kong. Methods-Two hundred eighty stroke patients consecutively admitted to the medical wards of a university-affiliated regional hospital were interviewed by a psychiatrist 3 months after stroke. The presence of dementia and vascular dementia was diagnosed according to the Diagnostic and Statistical Manual, 4th edition. In addition, a wide range of demographic and clinical variables were examined. Results-Fifty-five participants (20%) had PSDE. Univariate analysis found that PSDE was associated with age; level of education; prestroke Rankin Scale score; prestroke Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score; National Institutes of Health Stroke Scale (NIHSS) best language score, dysarthria score, and total score; urinary incontinence; cortical infarct; leukoaraiosis; bilateral lesions; number of lesions; involvement of middle cerebral artery circulation; and cerebral atrophy index. Multivariate logistic regression suggested that prestroke IQCODE score, NIHSS total score, leukoaraiosis, involvement of middle cerebral artery territory, and cerebral atrophy index were independent risk factors of PSDE. After removal of 22 patients with prestroke dementia, which was defined as a prestroke IQCODE score ≥4.0, the frequency of PSDE dropped to 15.5%. Furthermore, involvement of the middle cerebral artery territory and cerebral atrophy index were replaced by level of education and bilateral lesions as independent predictors in the final logistic model. Conclusions-PSDE is common among Chinese stroke patients in Hong Kong. Its frequency is comparable to that in white populations. The clinical determinants of PSDE, after the exclusion of patients with prestroke dementia, include premorbid level of cognitive function, severity of stroke, leukoaraiosis, level of education, and bilateral lesions.",adult;aged;article;brain atrophy;Chinese;cognition;computer assisted tomography;dementia;disease severity;education;female;human;leukoaraiosis;major clinical study;male;nuclear magnetic resonance imaging;prediction;prevalence;priority journal;rating scale;risk factor;cerebrovascular accident,"Tang, W. K.;Chan, S. S. M.;Chiu, H. F. K.;Ungvari, G. S.;Wong, K. S.;Kwok, T. C. Y.;Mok, V.;Wong, K. T.;Richards, P. S.;Ahuja, A. T.",2004,,,0,
904,Diffusion characteristics of the fornix in patients with Alzheimer's disease,"White matter degradation is a major part of the pathogenesis of Alzheimer's disease (AD). The fornix is the predominant outflow tract from the hippocampus, and alterations to its microstructure in patients with AD are still being explored. Diffusion tensor imaging (DTI) is an in vivo neuroimaging technique that can provide unique information about alterations in tissue microstructure, which can indicate underlying neurobiological process at the microstructural level. In this prospective study, DTI was used to assess and analyze the microstructural features of the fornix in subjects with AD (n = 17), mild cognitive impairment (MCI; n = 12) and healthy controls (n = 17). DTI was performed using Explore DTI software and the FSL package. Within the fornix, patients with AD showed decreased fractional anisotropy values and length of fiber tracts of the fornix relative to healthy controls, but higher mean diffusivity values. MCI subjects showed a trend towards elevated mean diffusivity values in the fornix. The data suggest that DTI provides supporting information on the microstructural alteration of the fornix in patients with AD, and that these diffusion characteristics of the fornix may be helpful for the clinical diagnosis of AD.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ diagnostic imaging;Anisotropy;Cognitive Dysfunction/diagnosis/ diagnostic imaging;Diffusion Tensor Imaging/ methods;Female;Fornix, Brain/ diagnostic imaging/pathology;Humans;Male;Middle Aged;Prospective Studies;Reproducibility of Results;Sensitivity and Specificity;Alzheimer's Disease;Fornix;Fractional anisotropy;Mean diffusion","Tang, S. X.;Feng, Q. L.;Wang, G. H.;Duan, S.;Shan, B. C.;Dai, J. P.",2017,Jul 30,,0,905
905,Diffusion characteristics of the fornix in patients with Alzheimer's disease,"White matter degradation is a major part of the pathogenesis of Alzheimer's disease (AD). The fornix is the predominant outflow tract from the hippocampus, and alterations to its microstructure in patients with AD are still being explored. Diffusion tensor imaging (DTI) is an in vivo neuroimaging technique that can provide unique information about alterations in tissue microstructure, which can indicate underlying neurobiological process at the microstructural level. In this prospective study, DTI was used to assess and analyze the microstructural features of the fornix in subjects with AD (n = 17), mild cognitive impairment (MCI; n = 12) and healthy controls (n = 17). DTI was performed using Explore DTI software and the FSL package. Within the fornix, patients with AD showed decreased fractional anisotropy values and length of fiber tracts of the fornix relative to healthy controls, but higher mean diffusivity values. MCI subjects showed a trend towards elevated mean diffusivity values in the fornix. The data suggest that DTI provides supporting information on the microstructural alteration of the fornix in patients with AD, and that these diffusion characteristics of the fornix may be helpful for the clinical diagnosis of AD.",Alzheimer's Disease;Fornix;Fractional anisotropy;Mean diffusion,"Tang, S. X.;Feng, Q. L.;Wang, G. H.;Duan, S.;Shan, B. C.;Dai, J. P.",2016,Oct 01,,0,
906,Arg332Cys mutation of NOTCH3 gene in the first known Taiwanese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"The phenotype and genotype of cerebral autosomal dominant arteriopathy and subcortical infarcts and leukoencephalopathy (CADASIL) in Caucasians have been well characterized, but CADASIL is less recognized in Asian populations. Here we investigated the first known Taiwanese family affected by CADASIL and identified an uncommon NOTCH3 mutation. The family had clinical manifestations in affected members including recurrent strokes, early dementia, and depression, but not migraine. A skin biopsy in the proband patient showed characteristic pathological findings of CADASIL on electron microscopy. Afterward, genetic analysis found an Arg332Cys mutation at exon 6 of NOTCH3. Neuropsychological evaluation showed vascular dementia in two of four affected people. Head MRI showed multiple infarcts in bilateral basal ganglia, thalami, periventricular white matter, external capsules, and brainstem, but involvement of the anterior temporal pole was found only in two people with milder symptoms. To our knowledge, the Arg332Cys NOTCH3 mutation at exon 6, which was identified in the studied family, has not been reported in Asian populations. Our findings emphasize the importance of genetic analysis of NOTCH3 for Asians with a phenotype typical of CADASIL. © 2004 Elsevier B.V. All rights reserved.",arginine;cysteine;Notch3 receptor;adult;article;Asian;basal ganglion;brain infarction;brain stem;CADASIL;case report;clinical feature;dementia;depression;electron microscopy;exon;family study;female;gene mutation;genetic analysis;human;male;migraine;multiinfarct dementia;mutational analysis;neuropathology;neuropsychological test;nuclear magnetic resonance imaging;phenotype;priority journal;recurrent disease;skin biopsy;cerebrovascular accident;Taiwan;thalamus;white matter,"Tang, S. C.;Lee, M. J.;Jeng, J. S.;Yip, P. K.",2005,,,0,
907,Skin biopsy in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy,,Notch3 receptor;adult;article;basement membrane;brain artery;CADASIL;case report;cell granule;electron microscopy;family history;gene;gene mutation;granular osmiophilic material;human;human tissue;leukoencephalopathy;male;Notch 3 gene;nuclear magnetic resonance imaging;sensitivity and specificity;skin biopsy,"Tang, S. C.;Chiu, Y. H.;Jeng, J. S.",2004,,,0,
908,Aberrant white matter networks mediate cognitive impairment in patients with silent lacunar infarcts in basal ganglia territory,"Silent lacunar infarcts, which are present in over 20% of healthy elderly individuals, are associated with subtle deficits in cognitive functions. However, it remains largely unclear how these silent brain infarcts lead to cognitive deficits and even dementia. Here, we used diffusion tensor imaging tractography and graph theory to examine the topological organization of white matter networks in 27 patients with silent lacunar infarcts in the basal ganglia territory and 30 healthy controls. A whole-brain white matter network was constructed for each subject, where the graph nodes represented brain regions and the edges represented interregional white matter tracts. Compared with the controls, the patients exhibited a significant reduction in local efficiency and global efficiency. In addition, a total of eighteen brain regions showed significantly reduced nodal efficiency in patients. Intriguingly, nodal efficiency-behavior associations were significantly different between the two groups. The present findings provide new aspects into our understanding of silent infarcts that even small lesions in subcortical brain regions may affect large-scale cortical white matter network, as such may be the link between subcortical silent infarcts and the associated cognitive impairments. Our findings highlight the need for network-level neuroimaging assessment and more medical care for individuals with silent subcortical infarcts.","Aged;Basal Ganglia/ pathology;Brain Infarction/complications/ pathology;Cognition Disorders/etiology/ pathology;Databases, Factual;Female;Humans;Male;Middle Aged;White Matter/ pathology","Tang, J.;Zhong, S.;Chen, Y.;Chen, K.;Zhang, J.;Gong, G.;Fleisher, A. S.;He, Y.;Zhang, Z.",2015,Sep,10.1038/jcbfm.2015.67,0,
909,Coexisting cortical atrophy plays a crucial role in cognitive impairment in patients with moderate to severe cerebral small vessel disease,"Whether white matter lesion (WML) is associated with vascular cognitive impairment in cerebral small vessel disease (CSVD) remains controversial; some severe CSVD patients retain normal cognitive function, and cortical thinning associated with WMLs has also been recently reported. The contribution of cortical atrophy to vascular cognitive impairment in severe CSVD and whether WML affects cortical atrophy remain unknown. From November 2012 to January 2015, 50- to 80-year-old patients with moderate to severe WMLs or more than four lacunar infarctions and cognitive complaints, excluding those with large vascular diseases diagnosed by transcranial cerebral Doppler, were recruited. The patients were divided into CSVD groups with or without vascular cognitive impairment-no dementia (VCIND) according to scores on neuropsychological tests that evaluated five cognitive domains. Based on these results, 16 patients were included in the CSVD with VCIND group, and 12 were included in the CSVD without VCIND group. T1, T2, 3D-MPRAGE, and diffusion tensor imaging were performed, and gray matter volume and FA values were compared between the two groups. Gray matter volume, especially in the frontal cortex, bilateral calcarine sulcus, and fusiform gyrus, was considerably lower in the CSVD with VCIND patients, with 24,619 fewer voxels. In addition, the FA values of 1,583 voxels were lower in the CSVD patients with VCIND than in those without. In conclusion, cortical atrophy is associated with cognitive impairment in moderate to severe WML or lacunar infarction patients, suggesting that cortical atrophy might be secondary to white matter damage in vascular cognitive impairment caused by CSVD.",adult;aged;article;Boston naming test;brain cortex atrophy;cerebrospinal fluid analysis;cerebrovascular disease;clock drawing test;cognitive defect;corona radiata (brain);dementia;diffusion tensor imaging;executive function;female;gray matter;human;image processing;major clinical study;male;radiofrequency;Rey auditory verbal learning test;Rey Osterrieth complex figure test;stenosis;stroke patient;Stroop test;symbol digit modalities test;trail making test;voxel based morphometry;white matter lesion;Magneton Verio 3T,"Tang, J.;Shi, L.;Zhao, Q.;Zhang, M.;Ding, D.;Yu, B.;Fu, J.",2017,,,0,
910,"Clinical, neuropsychological and computertomography research in patients with Parkinson disease and dementia","The dementia (D) syndrome in patients with Parkinson disease is still an often discussed question. The grate range of variability's, from one point of vue due to different criterion for diagnosis performation. Another point are the differences of it methodological researchment. The aim of the study is to perform and analyze our results of clinical, neuropsyhological and computer tomography (CT) investigation in 20 patients with various forms of Parkinson's disease, different duration of the illness and combined therapy. Neuropsyhological researchment includes baterry of the following neuropsyhological tests to define the D; MMSM, Scale for D on Blessed, scale for differential diagnosis of V. Hachinsky, scale of depression and anxiety based on Zung. The progress of D was based on DCM IV criterion. CT investigation to perform the type, range and main localisation of brain atrophy was based on precise ventriculometric measurements which includes 10 parameters. The results suggest correlation of cortical atrophy and lateral ventricular enlargment with the range of performation of D syndrome. There was no cerebellar atrophy foundings in any of the patients. Four of them was with multi-infarct encefalopaty, found by CT investigation.",article;brain atrophy;brain ventriculography;cerebellum atrophy;clinical article;clinical examination;clinical feature;computer assisted tomography;dementia;disease course;human;multiinfarct dementia;neuropsychology;Parkinson disease,"Taneva, N.;Tsonev, V.",1998,,,0,
911,CT study of brain atrophy in patients with dementia,"In most patients presenting Parkinson's disease, multiple cerebral infarctions and multiple sclerosis, cognitive impairment is often met with and by no means considered as unusual. It is the basic clinical symptom of Alzheimer's disease. Computed tomography, along with psychometric tests, is an important stage in identifying the morphological substrate of dementia - brain atrophy. The purpose of the work is to present and analyze the results of CT study of brain atrophy in various dementia types. Thirty patients with parkinsonism + dementia, ten multiple sclerosis and thirty - vascular dementia (multiinfarction dementia) are covered by the study. CT assessment of brine atrophy is done against the background of high-precision ventriculometric measurements, aimed at assaying the pattern (internal/external hydrocephaly), manifestation degree and predilected location of atrophic changes in the different dementia types. Each group with dementia has characteristic features of its own, with brain atrophy being most markedly expressed in vascular dementia. A positive correlation between brain atrophy degree and severity of cognitive disorders is found.",adult;aged;article;brain atrophy;clinical article;computer assisted tomography;dementia;disease severity;human;multiinfarct dementia;multiple sclerosis;neuroradiology;Parkinson disease,"Taneva, N.",2000,,,0,
912,A radiologic study of dynamic processes in lacunar dementia,"Using magnetic resonance imaging and digitized brain computed tomography, we evaluated 33 elderly patients with documented lacunar stroke and divided them into three groups (nondemented, n = 15; borderline, n = 9; and demented, n = 9) by neuropsychological assessments and DSM III criteria. We evaluated the extent of white matter lesions and the degree of atrophy of specific anatomic structures, such as the corpus callosum, using magnetic resonance imaging and quantified the volumes of the ventricles, the subarachnoid spaces, and the brain parenchyma using digitized brain computed tomography. Our results show that both borderline and demented patients had significantly more extensive white matter lesions than nondemented patients, indicating a significant relation between the extent of white matter lesions and intellectual decline. In addition, borderline and demented patients had significantly larger ventricles and more brain atrophy than nondemented patients; demented patients also had significantly larger subarachnoid spaces than nondemented patients and more brain atrophy than borderline patients. Our findings suggest that in most patients with lacunar stroke, periventricular and subcortical white matter lesions with subsequent white matter atrophy first induce ventricular enlargement, followed by generalized brain atrophy, resulting in dementia.","Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Dementia, Multi-Infarct/ pathology/radiography;Humans;Magnetic Resonance Imaging;Middle Aged;Neuropsychological Tests;Tomography, X-Ray Computed","Tanaka, Y.;Tanaka, O.;Mizuno, Y.;Yoshida, M.",1989,Nov,,0,
913,Characteristics of MRI features in Alzheimer's disease patients predicting response to donepezil treatment,"We attempted to investigate whether morphological features as shown on magnetic resonance imaging (MRI) predict response to donepezil treatment in patients with Alzheimer's disease (AD). Sixty-three patients with AD were divided into responders (n = 16) and non-responders (n = 47) based on the changes in the MMSE score between baseline and endpoint. Atrophy of the substantia innominata was more pronounced in responders than non-responders. Although no significant difference in the medial temporal lobe atrophy between responders and non-responders was found, magnetization transfer ratios (MTRs) of the hippocampus and parahippocampus, indicators of structural damage, in the non-responder group were significantly reduced compared to those in the responder group. There were no significant differences in the severity of white matter lesions between the two groups. Logistic regression analysis revealed that the overall discrimination rate was 81%, with 85% of non-responders and 69% of responders, through measurement of the thickness of the substantia innominata and MTR of the hippocampus and parahippocampus. These results suggest that AD patients who show more severe cholinergic dysfunction and less severe structural damage of the hippocampus and parahippocampus as shown on MRI are likely to respond to donepezil treatment.","Aged;Aged, 80 and over;Alzheimer Disease/ drug therapy/psychology;Brain/ pathology;Female;Hippocampus/pathology;Humans;Indans/ therapeutic use;Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Middle Aged;Nootropic Agents/ therapeutic use;Piperidines/ therapeutic use","Tanaka, Y.;Hanyu, H.;Sakurai, H.;Shimizu, S.;Takasaki, M.",2003,May,,0,
914,A case of strategic-infarct mild cognitive impairment,"Introduction: Although poststroke dementia has been investigated, patients with mild cognitive impairment (MCI) after stroke have received less attention, especially if there is cognitive decline in the absence of focal stroke symptoms. Case Report: We report an 80-year-old female referred to our memory clinic with a 6-month history of amnestic symptoms. Neuropsychological evaluation demonstrated a marked decline in short-term memory, without anosognosia, aphasia, motor deficit, or sensory disturbance. A brain magnetic resonance imaging performed 2 months after the onset of her symptoms revealed a lacunar infarction in the genu of the right internal capsule extended to the anterior thalamus. This lesion had not been present in a previous magnetic resonance imaging obtained 2 months before her amnestic symptoms appeared. Conclusions: The patient reported here demonstrated the evolution of MCI in the setting of a newly emergent lacunar infarction in the genu of the right internal capsule extended to the anterior thalamus. One possible mechanism for amnestic symptoms from a lacunar infarct in this location might be thalamocortical disconnection leading to ""strategic-infarct MCI."".Copyright © 2012 by Lippincott Williams & Wilkins.",,"Tanaka, H.;Hoshino, Y.;Watanabe, Y.;Sakurai, K.;Takekawa, H.;Hirata, K.",2012,July,,0,
915,Computed tomography and cerebral blood flow correlations of mental changes in chronic subdural hematoma,"To elucidate the pathophysiology of mental disturbances associated with chronic subdural hematoma, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced computed tomographic scans in 12 patients who had chronic subdural hematomas and manifested mental disturbances. In 2 patients who had no headache or hemiparesis, minimal mass effect, and severe multiple infarctions on computed tomographic scan, mentation did not improve after surgery. The CBF reduction was severe, and it further deteriorated after surgery. On the other hand, mentation improved to a varied extent in the other 10 patients, who had headache and/or hemiparesis and minimal, moderate, or severe mass effect and minimal or moderate multiple infarctions on computed tomographic scan. The CBF reduction was diffuse on both sides, but was more marked in the thalamus and putamen than it was in the cortex and subcortex. It was restored after surgery, but insufficiently. The restoration rate was statistically significant only in the thalamus, on both sides (with and without hematoma) (P < 0.05). Dementia scores and CBF values after surgery were correlated on the side with the hematoma in the frontal cortex and thalamus (P < 0.01) and in the hemisphere and temporoparietal cortex (P < 0.05). There was no correlation on the side with the hematoma in the occipital cortex, putamen, and frontal and temporoparieto-occipital subcortices or on the side without the hematoma. The thalamus undergoes displacement and distortion by the hematoma, which in turn leads to changes in consciousness. Postoperative residual mental deficits consist primarily of dementia related to preexisting multiple infarctions. Surgical benefits tend to be limited to disturbance of consciousness and not to other categories of mental function.",adult;aged;article;blood flowmetry;brain blood flow;clinical article;clinical feature;computer assisted tomography;consciousness disorder;dementia;female;hematoma;human;male;mental disease;pathophysiology;postoperative complication;preoperative evaluation;priority journal;subdural hematoma;surgical technique,"Tanaka, A.;Kimura, M.;Yoshinaga, S.;Ohkawa, M.",1992,,,0,
916,Magnetization transfer ratio of white matter hyperintensities in subcortical ischemic vascular dementia,"BACKGROUND AND PURPOSE: In subjects with subcortical ischemic vascular dementia (SIVD), tissue vacuolization, myelin pallor, and demyelination have been found on pathologic examination of white matter signal hyperintensities (WMSH). Magnetization transfer ratio (MTR) values provide a potential measure of compromised white matter integrity. The purpose of this study was to determine if there were differences in MTR of WMSH between subjects with SIVD and cognitively normal healthy control subjects. METHODS: Fifteen subjects with SIVD and 16 control subjects of comparable age and sex were studied. MTR images were coregistered to MR images segmented into tissue classes (gray matter, white matter, CSF, WMSH, and lacunar infarcts). MTR of WMSH was compared across groups and examined by WMSH location, size, and total burden. RESULTS: WMSH burden was greater in SIVD patients than in control subjects (2.4% vs 0.67%). MTR of WMSH did not differ between groups, but MTR of periventricular WMSH was lower in SIVD patients than in control subjects (37.6% vs 39.4%). Even after accounting for covariant effects of lesion burden, there was still a trend toward reduced periventricular WMSH MTR in the group with dementia. There was no correlation between WMSH MTR and WMSH lesion size. CONCLUSION: These findings are consistent with observations that pathologic changes in vascular dementia are most severe in the periventricular white matter and suggest that insight into the pathophysiology of SIVD might be gleaned from studies of the periventricular region.","Aged;Aged, 80 and over;Brain/ pathology;Brain Ischemia/complications;Dementia, Vascular/ diagnosis/etiology/pathology;Female;Humans;Magnetic Resonance Imaging;Male","Tanabe, J. L.;Ezekiel, F.;Jagust, W. J.;Reed, B. R.;Norman, D.;Schuff, N.;Weiner, M. W.;Chui, H.;Fein, G.",1999,May,,0,
917,Tissue segmentation of the brain in Alzheimer disease,"PURPOSE: To compare brain tissue in patients with Alzheimer disease with that in elderly control subjects by using high-resolution MR imaging and quantitative tissue-segmentation techniques. METHODS: MR imaging of the brain was performed in 21 patients with Alzheimer disease and 17 control subjects. A computerized segmentation program was used to quantify volumes of ventricular and sulcal cerebrospinal fluid (CSF), white matter, cortical gray matter, and white matter signal hyperintensity. Statistical analysis was performed using analysis of variance. RESULTS: We found a significant decrease in total brain tissue and cortical gray matter and an increase in the ventricular and sulcal CSF in Alzheimer patients compared with control subjects. There was no difference in the volume of white matter. More white matter signal hyperintensities were found in Alzheimer patients, and a significant interaction between age and group was noted. Neuropsychological test scores correlated significantly with sulcal CSF in patients with Alzheimer disease. CONCLUSION: Semiautomated segmentation of MR images of the brains of patients with Alzheimer disease reveals significant brain atrophy attributable to loss of cortical gray matter, which is compatible with the pathologic features of Alzheimer disease. There is also a significant increase in white matter signal hyperintensities. Tissue segmentation may increase our understanding of dementia but, as yet, when used alone, it does not play a role in the premorbid diagnosis of Alzheimer disease.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Atrophy;Brain/ pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Cerebrospinal Fluid/physiology;Diagnosis, Differential;Female;Humans;Image Processing, Computer-Assisted/ instrumentation;Magnetic Resonance Imaging/ instrumentation;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests","Tanabe, J. L.;Amend, D.;Schuff, N.;DiSclafani, V.;Ezekiel, F.;Norman, D.;Fein, G.;Weiner, M. W.",1997,Jan,,0,
918,Identification of a known mutation in Notch 3 in familiar CADASIL in China,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations. Methods and Results: We genotyped members of a 5-generational Han Chinese family with CADASIL patients and identified an R133C mutation in the NOTCH3 gene. Clinical analysis demonstrated that the penetrance of the mutation was not complete. Five of the mutation carriers, not exposed to the known vascular risk factors, did not show any clinical feature of CADASIL, suggesting the importance of environmental factors to the development of this disease. Conclusions: Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL.",arginine;cysteine;Notch3 receptor;adult;aged;amino acid sequence;amino acid substitution;article;CADASIL;China;Chinese;clinical article;clinical assessment;clinical feature;codon;DNA sequence;dysarthria;environmental factor;exon;exon 4;facial nerve paralysis;family study;female;gene;gene mutation;genotype;hemiparesis;heterozygote;human;jaw opening reflex;male;Notch 3 gene;nuclear magnetic resonance imaging;palmomental reflex;pedigree;penetrance;reflex;risk factor;Romberg sign;tendon reflex;tongue paralysis;vomiting reflex,"Tan, Z. X.;Li, F. F.;Qu, Y. Y.;Liu, J.;Liu, G. R.;Zhou, J.;Zhu, Y. L.;Liu, S. L.",2012,,,0,
919,Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging,"OBJECTIVE: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort. METHODS: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 +/- 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE epsilon4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D). RESULTS: Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: beta +/- SE = -0.49 +/- 0.19; p = 0.009, and 0.12 +/- 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and omega-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory (beta +/- SE = -0.47 +/- 0.18; p = 0.008), executive function (beta +/- SE = -0.07 +/- 0.03; p = 0.004), and abstract thinking (beta +/- SE = -0.52 +/- 0.18; p = 0.004) in model A, the results remaining significant in all models. CONCLUSION: Lower RBC DHA levels are associated with smaller brain volumes and a ""vascular"" pattern of cognitive impairment even in persons free of clinical dementia.","Aged;Aged, 80 and over;Aging/ metabolism/psychology;Alzheimer Disease/metabolism/psychology;Brain/ metabolism;Cognition/physiology;Dementia/metabolism/psychology;Erythrocytes/ metabolism;Fatty Acids, Omega-3/ metabolism;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Risk Factors","Tan, Z. S.;Harris, W. S.;Beiser, A. S.;Au, R.;Himali, J. J.;Debette, S.;Pikula, A.;Decarli, C.;Wolf, P. A.;Vasan, R. S.;Robins, S. J.;Seshadri, S.",2012,Feb 28,10.1212/WNL.0b013e318249f6a9,0,
920,Micro-structural white matter abnormalities in type 2 diabetic patients: a DTI study using TBSS analysis,"INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have usually been found cognitive impairment associated with brain white matter (WM) abnormalities. However, findings have varied across studies, and any potential relationship with Alzheimer's disease (AD) remains unclear. The aim of this study was to assess the whole-brain WM integrity of T2DM patients and to compare our findings with those of published AD cases. METHODS: In this study, we used diffusion tensor imaging (DTI) combined with tract-based spatial statistics (TBSS) to investigate whole-brain WM abnormalities in 48 T2DM patients and 48 healthy controls. The effects of age and gender were also evaluated. RESULTS: In our study, significantly decreasing FA and increasing MD and DA values (P<0.05) were found in some WM regions closely related to the default mode network (DMN), including cingulum, the right frontal lobe involving the right uncinate fasciculus (UF), bilateral parietal lobes involving the superior longitudinal fasciculus (SLF) and the inferior longitudinal fasciculus (ILF), and the right middle temporal gyrus (MTG) involving the UF and the ILF. We also found abnormalities in the thalamus involving the fornix (FX), anterior thalamic radiation (ATR), and posterior thalamic radiation (PTR). The damaged regions above are similar to those found in patients with AD, as reported in previous studies. CONCLUSION: The present study not only provides useful information about the WM regions and tracts affected by T2DM but also offers insight into the underlying neuropathological process in T2DM patients and the relationship between T2DM and AD.",Default mode network;Diffusion tensor imaging;Thalamus;Tract-based spatial statistics;Type 2 diabetes mellitus,"Tan, X.;Fang, P.;An, J.;Lin, H.;Liang, Y.;Shen, W.;Leng, X.;Zhang, C.;Zheng, Y.;Qiu, S.",2016,Dec,,0,
921,Assessment of amyloid β in pathologically confirmed frontotemporal dementia syndromes,"Introduction The diagnostic utility of in vivo amyloid β (Aβ) imaging to aid in the clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease remains unclear without data on the prevalence and severity of Aβ in pathologically confirmed FTD syndromes. Methods Aβ was assessed in 98 autopsy-confirmed FTD and 36 control cases, and the pathological accuracy of 11C-Pittsburgh compound B (PiB)–positron emission tomography imaging was assessed in a subset of FTD cases (n = 15). Results Aβ was identified in a similar proportion of FTD syndromes and age-matched controls and increases with age. Alzheimer's disease pathology was identified in all cases with high PiB retention and in one case with low PiB retention. We further demonstrate a strong regional correlation between volume fraction of histological Aβ with PiB standard uptake value ratio scaled to the white matter. Discussion The present study provides a pathologic reference to assist in the interpretation of in vivo assessments in FTD syndromes.",amyloid beta protein;carbon 11;Pittsburgh compound B;adult;aged;Alzheimer disease;article;autopsy;cohort analysis;controlled study;correlation analysis;female;frontotemporal dementia;histology;human;in vivo study;major clinical study;male;positron emission tomography;white matter,"Tan, R. H.;Kril, J. J.;Yang, Y.;Tom, N.;Hodges, J. R.;Villemagne, V. L.;Rowe, C. C.;Leyton, C. E.;Kwok, J. B. J.;Ittner, L. M.;Halliday, G. M.",2017,,10.1016/j.dadm.2017.05.005,0,
922,Assessment of amyloid beta in pathologically confirmed frontotemporal dementia syndromes,"INTRODUCTION: The diagnostic utility of in vivo amyloid beta (Abeta) imaging to aid in the clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease remains unclear without data on the prevalence and severity of Abeta in pathologically confirmed FTD syndromes. METHODS: Abeta was assessed in 98 autopsy-confirmed FTD and 36 control cases, and the pathological accuracy of (11)C-Pittsburgh compound B (PiB)-positron emission tomography imaging was assessed in a subset of FTD cases (n = 15). RESULTS: Abeta was identified in a similar proportion of FTD syndromes and age-matched controls and increases with age. Alzheimer's disease pathology was identified in all cases with high PiB retention and in one case with low PiB retention. We further demonstrate a strong regional correlation between volume fraction of histological Abeta with PiB standard uptake value ratio scaled to the white matter. DISCUSSION: The present study provides a pathologic reference to assist in the interpretation of in vivo assessments in FTD syndromes.",11C-Pittsburgh compound B;Alzheimer's disease;Amyloid beta;Diagnostic;Frontotemporal dementia syndromes,"Tan, R. H.;Kril, J. J.;Yang, Y.;Tom, N.;Hodges, J. R.;Villemagne, V. L.;Rowe, C. C.;Leyton, C. E.;Kwok, J. B. J.;Ittner, L. M.;Halliday, G. M.",2017,,,0,
923,Characteristics of CADASIL in Chinese mainland patients,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been reported in many geographical regions. However, relatively few reports about CADASIL in Chinese were reported. Materials and Methods: We retrospectively collected and analyzed clinical characteristics, magnetic resonance (MRI) features and genetic data of 52 Chinese mainland CADASIL patients. Results: Mean age of onset was 42.43 years. The primary clinical manifestations included: Ischemic stroke/transient ischemic attack (62.5%), primary intracerebral hemorrhage (25%), vertigo (25%), migraine (39.58%), dementia (18.75%) and emotional disturbance (20.83%). The most frequently observed MRI abnormalities were hyperintensity in the cerebral white matter on T2-weighted images and multiple infarcts, high-signal lesions on T2 images in anterior temporal lobes and external capsule were uncommon. The highest mutation frequency was in exon regions, 4 and 3, followed by exon 11. Granular osmiophilic material (GOM) was identified in 66.67% of the cases examined with biopsy. Conclusions: Most characteristics of Chinese mainland CADASIL patients are similar to those of CADASIL patients living in other regions. However, the prevalence of primary intracerebral hemorrhage and vertigo is much higher in Chinese mainland CADASIL patients. Significant leukoaraiosis in anterior temporal poles on T2-weighted image are uncommon. Exons 3 and 4 are the mutation hotspots.",,"Tan, Q. C.;Zhang, J. T.;Cui, R. T.;Xu, Q. G.;Huang, X. S.;Yu, S. Y.",2014,May-June,,0,
924,The case-control study on the relationship between cerebrovascular lesions and Alzheimer disease,"Objective: To explore the possible relationship between Alzheimer disease (AD) and cerebrovascular lesions, brain white matter lesions (WML) found in",,"Tan, J. P.;Wang, L. N.;Wang, Y.",2006,Jun,,0,
925,"Frontotemporal dementia with co-occurrence of astrocytic plaques and tufted astrocytes, and severe degeneration of the cerebral white matter: A variant of corticobasal degeneration?","We report two patients who exhibited frontotemporal dementia (FTD) with unusual neuropathological features. The ages of the patients at death were 65 and 67 years, the disease durations were 6 and 5 years, and the clinical diagnoses were Pick's disease and corticobasal degeneration (CBD), respectively. At autopsy, both cases exhibited neuropathological findings compatible with those of CBD, including atrophy of the frontal and parietal lobes, neuronal loss and gliosis in the cortical and subcortical regions, and presence of cortical ballooned neurons and astrocytic plaques (APs). In both cases, immunoblotting of insoluble tau exhibited the pattern of selective accumulation of four-repeat tau, a finding that is also compatible with CBD. However, severe degeneration was evident in the frontal and parietal white matter in both cases. Moreover, a striking finding was the widespread presence in the affected cortex of tufted astrocytes (TAs), which are characteristic of progressive supranuclear palsy (PSP). Neither co-occurrence of APs and TAs nor severe degeneration of the cerebral white matter is a feature of either CBD or PSP. No mutations were found in the tau gene in either case. In conclusion, the possibility that these two cases represent a new neuropathological phenotype of non-familial FTD rather than simply a variant of CBD cannot be completely excluded. © Springer-Verlag 2004.",tau protein;adult;article;astrocyte;autopsy;brain atrophy;case report;cause of death;clinical feature;corticobasal degeneration;diagnostic accuracy;differential diagnosis;disease course;fatality;female;frontotemporal dementia;genetic analysis;human;human tissue;immunoblotting;male;neuropathology;nuclear magnetic resonance imaging;Pick presenile dementia;plaque forming cell;pneumonia;priority journal;white matter,"Tan, C. F.;Piao, Y. S.;Kakita, A.;Yamada, M.;Takano, H.;Tanaka, M.;Mano, A.;Makino, K.;Nishizawa, M.;Wakabayashi, K.;Takahashi, H.",2005,,,0,
926,Magnetization transfer changes of grey and white matter in Parkinson's disease,"Since the attempt to evidence structural brain damage in Parkinson's disease (PD) by conventional magnetic resonance imaging (MRI) is usually disappointing, we have investigated whether the magnetization transfer ratio (MTR) can reflect changes in grey and white matter of PD patients. MTR was quantified in 44 regions of interest (ROIs) in both grey and white matter of 11 non-demented PD patients, ranging from 2 to 4 on the Hoehn and Yahr Scale, and eight age-matched healthy subjects. MTR differences between patients and controls were found in the supratentorial white matter and in the brainstem. In particular, lower MTR values were found in the paraventricular white matter of PD patients (p<0.05) while no differences were observed in corpus callosum, frontal, parietal, occipital lobes or centrum semiovalis. Lower MTR values were found in substantia nigra (p<0.001), red nucleus (p<0.05) and pons (p<0.05) of the patient group. No differences were discovered in basal ganglia and thalamus. These findings suggest that MTR measurements in the paraventricular white matter and brainstem may help to recognize a marker for probable PD.",Aged;Brain Stem/ pathology;Female;Humans;Magnetic Resonance Imaging;Magnetics;Male;Middle Aged;Paraventricular Hypothalamic Nucleus/ pathology;Parkinson Disease/ pathology,"Tambasco, N.;Pelliccioli, G. P.;Chiarini, P.;Montanari, G. E.;Leone, F.;Mancini, M. L.;Paciaroni, M.;Gallai, V.",2003,Apr,10.1007/s00234-002-0925-5,0,
927,Unexpected accumulation of thallium-201 in bilateral thalamic venous infarction induced by arteriovenous fistula in the posterior fossa: Report of a case,We encountered unexpected accumulation of thallium-201 in a patient with thalamic dementia resulting from bithalamic venous infarction induced by arteriovenous fistula in the posterior fossa. The site and degree of abnormal accumulation varied between early and delayed thallium-201 SPECT images. This unexpected and complicated accumulation of thallium-201 appeared to depend on not only breakdown of the blood-brain barrier but also on the hemodynamics of this type of venous infarction.,,"Tamamoto, F.;Nakanishi, A.;Takanashi, T.;Ishizaki, H.;Nagasawa, H.;Maehara, T.;Ohno, S.;Otsubo, Y.",2003,May,,0,
928,Skin biopsy is a useful tool for the diagnosis of atypical CADASIL: A case report,"A 57-year-old man developed migraine at the age of 25 years. Thereafter, he developed depression at the age of 50 years, and was admitted to a psychiatric hospital at the age of 54 years because of deteriorating depression. He returned to his work after receiving treatment for depression; however, he made mistakes several times in his work. He was referred to our hospital for further neurological evaluation. The results of the neurological examination performed on admission were unremarkable. His Mini Mental State Examination (MMSE) score was 24/30, and neuropsycological evaluations revealed executive dysfunction. There was no family history of dementia or cerebral infarction. Magnetic resonance fluid attenuated inversion recovery (MR FLAIR) image of the brain showed hyperintense lesions around the lateral ventricle without involvement in the temporal pole and external capsule. Despite a lack of family history of dementia and cerebral infarction and non-specific brain MRI findings, his history of headache and depression were suggestive of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, skin biopsy was performed; electron microscopy of the biopsied sample revealed granular osmio-philic material deposits. Genetic analysis of the NOTCH3 gene showed a missense mutation with substitution of R427C in exon 8, i.e., out of the hot-spot, exon 3, and 4. Thus, skin biopsy is a useful tool for diagnosing atypical CADASIL.",,"Tamaki, K.;Fukae, J.;Koga, K.;Nagatoshi, A.;Ueda, A.;Ouma, S.;Ando, Y.;Tsuboi, Y.",2015,1,,0,
929,Two siblings with adult-type metachromatic leukodystrophy: correlation between clinical symptoms and neuroimaging,"We reported two siblings with adult-type metachromatic leukodystrophy (MLD). Patient 1 was a 19-year-old male, and patient 2 was a 20-year-old female. Their initial symptoms were similar. They developed abnormal behavior and personality changes, poor concentration, and inappropriate smiling. In patient 1, his condition deteriorated and he developed incontinence. His attention span and verbal expression severely decreased. He had an inability to engage in meaningful conversation. The siblings were diagnosed as having MLD by marked reduced leukocyte arylsulfatase A activity. T2-weighted MRI of these two cases showed a high intensity area in the cerebral white matter. The high intensity areas of the cerebral white matter gradually spread over one year. However, SPECT of these cases showed only a few abnormal findings in the initial stage. Using SPECT, a reduction of regional cerebral blood flow (rCBF) spreading to the cerebral cortex was seen over one year after it was seen using MRI. The discrepancy between MRI and SPECT findings in the initial stage was characteristic. MLD is an important disease that involves white matter dementia. The discrepancy between MRI and SPECT is helpful to diagnose white matter dementia.",adult;article;attention deficit disorder;brain;case report;female;genetics;human;male;mental disease;metachromatic leukodystrophy;nuclear family;nuclear magnetic resonance imaging;pathology;personality disorder;scintiscanning;single photon emission computer tomography;speech disorder,"Tamagaki, C.;Murata, A.;Saito, A.;Kinoshita, T.",2000,,,0,
930,Adrenoleukodystrophy initially presenting with symptoms of dementia,"There is growing consensus that dementia caused by white matter alterations is called 'white matter dementia'. Because the symptoms of adrenoleukodystrophy (ALD) are associated with diffuse white matter dysfunction, ALD is categorized as white matter dementia. Herein, we describe the case of a 47-year-old man affected by ALD whose symptoms first appeared a few years earlier in the form of deteriorating personality and memory disturbances, heralded by neurological symptoms. On neuroimaging, a discrepancy was found between magnetic resonance imaging and single photon emission computed tomography in the early stage of the disease process. We suggest that this discrepancy may be an important finding in the diagnosis of early stage white matter dementia. © 2007 The Authors; Journal compilation © 2007 Japanese Psychogeriatric Society.",,"Tamagaki, C.;Murata, A.;Ohara, T.;Sakata, T.;Takase, K.;Okugawa, G.;Nobuhara, K.;Kinoshita, T.",2007,December,,0,
931,A 45-year-old man with peripheral monocytosis and right hemiparesis,"We report a 45-year-old man with monocytosis and right hemiparesis. The patient suffered from an acute myocardial infarction from which he recovered completely when he was 42 years old. One year prior to his death, he was found to have increase in monocyte count (35.5% of leukocytes) in peripheral blood and splenomegaly; he was admitted to the hematology service of our hospital. He was diagnosed as having chronic myelomonocytic leukemia after bone marrow examination. He was treated with radiation therapy with improvement in splenomegaly. In May of 1995, he had fever, anemia, and thrombocytopenia for which he needed daily blood transfusion. In November of 1995, he had an onset of weakness in his right hand, and neurologic consultation was asked for in November 27, 1995. Neurologic examination revealed a chronically ill Japanese man in no acute distress. He was alert and not demented. Higher cerebral functions were intact. Cranial nerve examination revealed right facial paresis of the central type. Motor-wise, he was right hemiparetic. Generalized muscle wasting was noted apparently due to the chronic debilitating disease. Deep tendon reflexes were within normal range in the right upper extremity, but were diminished in other areas. Sensation was intact, and no meningeal signs were noted. Pertinent laboratory findings were as follows: Hb 8 g/dl, RBC 238 x 104/μl, WBC 2,900/μl (band 1.0%, seg 18.5%, lym 28.0%, mono 44.0%, Baso 2.5%), Plt 13 x 104/μl, PT 16.6'/10.9', APTT 44.7'/35.0'. CSF contained 87 mg/dl of protein, 155 mg/dl of glucose and 2 mononuclear cells/μl. Bone marrow was slightly hypercellular with mild increase in blast forms. No chromosome abnormality was found. CT and MRI revealed a large mass in the left fronto-parietal region and the meninges showed marked thickening with enhancement after gadolinium-DTPA in MRI. The patient was treated with glycerol and steroid, but the subsequent course was complicated by a seizure, agitation, and pneumonia. He died from respiratory failure on January 13, 1996. The patient was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had chronic myelomonocytic leukemia with infiltration of leukemic cells into meninges and the parenchyme of the cerebrum. Thickening of the dura was thought to be in part a reaction to the subdural hematoma as well as to leukemic cells along the meninges. Postmortem examination revealed hypercellular bone marrow with increase in monocytic cells (more than 20%). The lungs showed pneumonia with scattered old tuberculous lesions. The heart showed an old myocardial infarction in the posterior wall of the left ventricle. The brain showed an old chronic subdural hematoma in the left fronto-temporal region and a cystic mass lesion in the left frontoparietal region. The mass was hypercellular and most of them were monocytes. The dura mater showed reactive thickening without leukemic cell infiltration. It was concluded that this patient had chronic myelomonocytic leukemia with a formation of leukemic mass in the brain. Pathologists thought that the mass was a hematogenous spread. It is rare for chronic myelomonocytic leukemia to form a mass lesion in the brain.",gadolinium pentetate;glucose;glycerol;protein;steroid;adult;article;blood cell count;blood transfusion;bone marrow examination;case report;cerebrospinal fluid examination;chronic myelomonocytic leukemia;computer assisted tomography;hemiparesis;human;male;monocytosis;neurologic examination;nuclear magnetic resonance imaging,"Takubo, H.;Hattori, N.;Irie, S.;Mizutani, Y.;Mori, H.;Suda, K.;Kondo, T.;Oshimi, K.;Mizuno, Y.",1998,,,0,
932,The VEGF gene polymorphism impacts brain volume and arterial blood volume,"Vascular endothelial growth factor (VEGF) plays a critical role in the angiogenesis and proliferation of various types of cells such as neurons, astroglia, and endothelial cells in the brain. A common polymorphism in the VEGF gene (-2578 C/A) is associated with circulating VEGF levels, cancers and Alzheimer's disease. Nonetheless, the effects of this polymorphism on normal human brain volume, arterial blood volume, and blood supply remain unclear. In this study, the effects of this polymorphism on the total gray matter volume (TGMV) and total white matter volume (TWMV) using T1-weighted structural images and the total arterial blood volume (TABV) and mean cerebral blood flow (mCBF) during rest using arterial spin labeling (ASL) in 765 young adult humans were investigated. Voxel-by-voxel whole-brain analyses of these measures were also performed. Multiple regression analyses with age and sex as covariates revealed that the VEGF genotype (number of C alleles) was significantly and positively correlated with TGMV, TWMV, and TABV as well as with regional gray and white matter volumes in widespread areas and regional arterial blood volume in some areas with high arterial blood volume. However, these regional associations were not seen when the corresponding global signal was included as a covariate in the multiple regression analyses, indicating that we failed to obtain evidence of region-specific associations between these brain measures and the genotype. The results suggest that the VEGF-2578C allele, is associated with changes in the vascular system that lead to increased blood volume and larger brain volume. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.",Vegf;blood volume;brain;brain volume;polymorphism,"Takeuchi, H.;Tomita, H.;Taki, Y.;Kikuchi, Y.;Ono, C.;Yu, Z.;Sekiguchi, A.;Nouchi, R.;Kotozaki, Y.;Nakagawa, S.;Miyauchi, C. M.;Iizuka, K.;Yokoyama, R.;Shinada, T.;Yamamoto, Y.;Hanawa, S.;Araki, T.;Kunitoki, K.;Sassa, Y.;Kawashima, R.",2017,Apr 12,,0,
933,Memory deficits in amyotrophic lateral sclerosis patients with dementia and degeneration of the perforant pathway. A clinicopathological study,"Degeneration of the perforant pathway, not extensively surveyed so far in amyotrophic lateral sclerosis (ALS) with dementia, was found in eight out of twelve autopsied patients with clinically detectable dementia. Because the severity of degeneration of the entorhinal cortex and that of spongiosis of the outer half of the molecular layer of the dentate gyrus were correlated in these eight patients, it is suspected that the degeneration of the perforant pathway may explain these concomitant lesions. This was further corroborated by occasional involvement of the parahippocampal white matter and subiculum, other components of this pathway. Moreover, six of them manifested clinically detectable memory deficits and three of them exhibited amnesia or episodic memory impairments similar to Alzheimer's disease (AD). Abnormal intensity restricted the dentate gyrus on brain magnetic resonance imaging in a severe case looks like the degeneration of the molecular layer. This involvement of the perforant pathway in ALS patients and its correlation to memory deficits should be taken in account for evaluation of dementia. © 2007 Elsevier B.V. All rights reserved.",,"Takeda, T.;Uchihara, T.;Mochizuki, Y.;Mizutani, T.;Iwata, M.",2007,15,,0,
934,[Progressive mental deterioration after radiotherapy in adult patients with brain tumors],"We report a study on changes of mental function in twenty five adult patients with cerebral low-grade gliomas after radiotherapy. None of them had shown mental deterioration before radiotherapy nor tumor recurrence after radiotherapy. Radiation was given at a dose of 48 to 78 Gy (mean: 54.2 Gy). Patients were assigned for mental functional levels according to Karnofsky performance scale (KPS) after radiotherapy. Ten patients (40%) were normal. Seven patients (28%) showed moderate disabilities and 8 (32%) severe disabilities. The median interval time from radiotherapy to the onset of mental deterioration was 2.5 years in the moderate group and 1.6 years in the severe group. CT findings in severe group demonstrated severe brain atrophy and diffuse low density in the white matter after radiotherapy. The risk factors responsible for progressive mental deterioration after radiotherapy may be radiation site and size (whole frontal lobe), total dose (over 60 Gy) and patients age at the time of radiotherapy (over 60 yrs).","Adult;Age Factors;Atrophy;Brain/pathology/radiation effects/radiography;Brain Neoplasms/*radiotherapy;Dementia/*etiology/radiography;Female;Glioma/*radiotherapy;Humans;Male;Middle Aged;Radiation Injuries/*etiology/radiography;Radiotherapy/*adverse effects/methods;Radiotherapy Dosage;Risk Factors;Tomography, X-Ray Computed","Takeda, N.;Tanaka, R.;Ibuchi, Y.;Hondou, H.",1989,Sep,,0,
935,Difficulty with learning of exercise instructions associated with 'working memory' dysfunction and frontal glucose hypometabolism in a patient with very mild subcortical vascular dementia with knee osteoarthritis,"We present a patient with no dementia, depression or apathy, who had difficulty in learning self-exercise instructions. The patient was an 80-year-old right-handed woman who was admitted to a rehabilitation unit to receive postoperative rehabilitation after a femoral neck fracture. She was instructed quadriceps isometric exercises to perform 10 repetitions and to hold each stretch for 10 s. She performed the exercise correctly with motivation, but she had difficulty in learning the number of repetitions and the duration of each stretch. She had no history of cerebrovascular accident and the neurological examination was normal. Neuropsychological testing, MRI and 18F-fluoro-D-glucose-positron emission tomography (FDG-PET) were performed to examine the neural mechanisms associated with this difficulty in learning instructions. Neuropsychological tests revealed dysfunction of working memory while other cognitive domains were relatively preserved. Her neuropsychological tests scores were (1) Mini-Mental State Examination: 24 (mild cognitive impairment), (2) Geriatric Depression Scale-15: 2 (no depression), (3) Apathy Scale: 2 (no apathy), (4) digit span forward: 5 (normal), (5) digit span backward: 2 (impaired), (6) visuospatial span forward: 4 (normal), (7) visuospatial span backward: 2 (impaired), (8) frontal assessment battery: 11 (normal), (9) Weigl test: 0 (impaired), (10) trail making test A: 52 s (normal), (11) train making test B: failed (impaired). T2-weighted and fluid-attenuated inversion recovery MRI showed high signal-intensity lesions in the cerebral deep white matter. FDG-PET revealed hypometabolic areas in the bilateral frontal lobes, particularly in the bilateral dorsolateral frontal area, anterior cingulate cortex and orbitofrontal cortex. One of the possible neural mechanisms underlying the learning difficulties in this patient may have been partial blockage of the cingulofrontal network by deep white matter lesions. Copyright 2013 BMJ Publishing Group. All rights reserved.",fluorodeoxyglucose;aged;apathy;Apathy Scale;article;brain function;cane;case report;depression;disease association;disease severity;female;femur neck fracture;follow up;frontal glucose hypometabolism;frontal lobe;Geriatric Depression Scale;glucose metabolism;human;isometric exercise;knee osteoarthritis;long term memory;memory disorder;Mini Mental State Examination;motor performance;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;osteosynthesis;physiotherapist;physiotherapy;positron emission tomography;priority journal;quadriceps femoris muscle;short term memory;subcortical vascular dementia;treatment outcome;verbal memory;working memory,"Takeda, K.;Meguro, K.;Tanaka, N.;Nakatsuka, M.",2013,,,0,
936,Frontal lobe dysfunction caused by multiple lacunar infarction in community-dwelling elderly subjects,"We examined the factors that influence frontal lobe function among 119 community-dwelling elderly subjects, based on magnetic resonance imaging (MRI) and clinical findings. We interviewed the subjects, and conducted a neurological examination, electrocardiogram, blood test, brain MRI examination, and cognitive function tests. The modified Stroop test and a personal computer version of the Wisconsin Card Sorting Test (WCST) were used to evaluate frontal lobe function. The subjects with impaired frontal lobe function defined by the modified Stroop test were significantly older, had more lacunar infarcts, and had lower HDL cholesterol values based on a logistic regression model. Among the aged who appear apparently normal, multiple lacunar infarcts are the cause of latent frontal lobe dysfunction. © 2003 Elsevier B.V. All rights reserved.",,"Takashima, Y.;Yao, H.;Koga, H.;Endo, K.;Matsumoto, T.;Uchino, A.;Sadanaga-Akiyoshi, F.;Yuzuriha, T.;Kuroda, Y.",2003,15,,0,
937,"Corticobasal degeneration as cause of progressive non-fluent aphasia: Clinical, radiological and pathological study of an autopsy case","A Japanese male developed gradual loss of spontaneous speech at age 60. Three years later meaningful speech had deteriorated to the point that it had become restricted to monotonous utterances. Neuropsychological examination at age 62 showed that he had severe non-fluent aphasia. A brain MRI demonstrated mild cortical atrophy with ischemic lesions in the cerebral white matter. He was diagnosed as having primary progressive aphasia. At age 63, he was admitted to the hospital to reevaluate the neurological condition. Neurologic examination showed severe non-fluent aphasia, hyperreflexia, snout and sucking reflexes. No alien hand was observed. He was able to walk, dress, wash himself and use chopsticks as well as name real objects. At age 65, 99mTc- hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO-SPECT) revealed diffuse cerebral hypoperfusion that was particularly prominent in the left frontal lobe. An MRI showed progressive cortical atrophy with the definite atrophy of the left paracentral gyrus. The hippocampal formation and putamen were also atrophic. He died of pneumonia at age 67. The brain weighed 810 g with atrophy of the frontal lobe, globus pallidus, enlargement of the lateral ventricles and depigmentation of the substantia nigra. Microscopic examination showed severe neuronal loss and gliosis in the cerebral cortex, globus pallidus interna and substantia nigra. Ballooned neurons were observed in the cerebral cortex. Gallyas-Braak method revealed numerous astrocytic plaques and argentophilic threads in the cerebrum. Clinical diagnosis of corticobasal degeneration sometimes is difficult in individuals with atypical clinical presentations. More exact clinical and radiological criteria may warrant a diagnosis of corticobasal degeneration. © 2006 Japanese Society of Neuropathology.",hexamethylpropylene amine oxime technetium tc 99m;adult;aged;article;astrocyte;autopsy;brain atrophy;brain cortex;brain perfusion;brain weight;case report;clinical feature;corticobasal degeneration;depigmentation;disease course;fluency disorder;frontal lobe;gliosis;globus pallidus;hippocampus;human;human tissue;hyperreflexia;Japan;lateral brain ventricle;male;microscopy;nerve cell;neuropsychology;non fluent aphasia;nuclear magnetic resonance imaging;pneumonia;primary progressive aphasia;priority journal;putamen;reflex;single photon emission computer tomography;speech disorder;speech intelligibility;substantia nigra;white matter,"Takao, M.;Tsuchiya, K.;Mimura, M.;Momoshima, S.;Kondo, H.;Akiyama, H.;Suzuki, N.;Mihara, B.;Takagi, Y.;Koto, A.",2006,,,0,
938,White matter T2 hyperintensity development and clinical deterioration after status epilepticus in a patient with dentatorubral-pallidoluysian atrophy,"Serial T2-weighted magnetic resonance imaging in a 29-year-old woman with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) demonstrated that a cerebral white matter hyperintensity appeared within 2 months after status epilepticus and persisted for more than 20 months. The patient had rapidly progressive mental regression and became akinetic after status epilepticus. The chronological relationship between the signal changes and the clinical deterioration suggested that the epilepsy, at least in part, contributed to the progression of white matter degeneration, the hallmark of DRPLA. © 2005 Elsevier B.V. All rights reserved.",,"Takamure, M.;Hirano, M.;Taoka, T.;Ueno, S.",2006,July,,0,
939,Diagnostic value of brain biopsy in intravascular large B-cell lymphoma mimicking progressive multifocal leukoencephalopathy: Case report,"We report a 68-years-old woman with systemic sclerosis and interstitial pneumonia (IP). She had developed subacute progressively encephalopathy and dementia while treated with oral cyclophosphamide and prednisolone. She admitted to our hospital because of syncope. Laboratory tests indicated slight elevated cerebrospinal fluid protein, and levels of serum C-reactive protein (CRP), levels of soluble IL-2 receptor was normal. But, magnetic resonance imaging (MRI) of the brain showed multiple infarct-like lesions mainly in the white matter, which mimics progressive multiple leukoencephalopathy (PML). Twenty days after admission, the retested MRI of the brain disclosed initial lesions progressively enlarged and numbers of the lesions were increased. The polymerase chain reaction (PCR) for JC virus of cerebrospinal fluid was negative. To make diagnosis, brain biopsy was performed. Microscopic examination revealed that small vessels were filled with lymphoma cells (CD20+, CD79+, CD3-), and intravascular lymphoma (IVL) was diagnosed. She treated with regimens of R-CHOP. After chemotherapy her consciousness and dementia were gradually improved. IVL of central nerve system (CNS) is a rare disease, and its common symptoms are ischemia, infarction and dementia. Diagnosis of IVL of CNS is difficult when the lesion mimics PML, and patient with similar laboratory examinations and radiographic findings of PML should undergo brain biopsy detected malignant cell in small vessels, which is a value of diagnosis. © 2014 The Japan Society for Clinical Immunology.",,"Takamine, Y.;Ikumi, N.;Onoe, H.;Hayase, M.;Nagasawa, Y.;Sakagami, M.;Sugiyama, K.;Nakahawa, S.;Uchino, Y.;Takahashi, H.;Hirabayashi, Y.;Nozaki, T.;Miura, K.;Inomata, H.;Iriyama, N.;Shiraiwa, H.;Kobayashi, S.;Kitamura, N.;Hatta, Y.;Matsukawa, Y.;Takei, M.",2014,2014,,0,
940,A case of epileptic seizures associated with non-ketotic hyperglycemia mimicking Creutzfeldt-Jakob disease on diffusion weighted MRI,"Magnetic resonance imaging findings of epileptic seizures associated with non-ketotic hyperglycemia are characterized by hyperintensity in gray and/or white matter on T2-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion weighted images. However, these findings are very similar to those of Creutzfeldt-Jakob disease. We report a case of epileptic seizures associated with non-ketotic hyperglycemia mimicking Creutzfeldt-Jakob disease on diffusion weighted MRI.",,"Takaki, Y.;Ogawa, T.;Kamata, N.;Sakai, F.;Ushimi, T.;Kishida, S.",2006,2006,,0,
941,Cerebrovascular CO2 reactivity in patients with dementia due to multiple infarction in the territory of the perforating artery,"In order to clarify the pathophysiology of dementia due to multiple infarction in the territory of the perforating artery, the reactivity of cerebral vessels to increased carbon dioxide tension was examined in patients with multiple cerebral infarction with or without dementia. The subjects studied were 11 patients with multi-infarct dementia (MID) (age 57-82 years old, mean +/- S.D. 72 +/- 8) and 16 patients with multiple infarction without dementia (MI) (age 51-81 years old, mean +/- S.D. 69 +/- 9). The diagnosis of cerebral infarction was based on the clinical signs and symptoms and findings of magnetic resonance imaging (MRI). Only patients with cerebral infarction located in the perforator territories were included in this study. Dementia was diagnosed by DSM-IIIR criteria. The extent of periventricular high intensity area (PVH) on the T2-weighted image of MRI was classified into 3 subgroups by the criteria of Gerard et al with some modifications. Cerebral blood flow (CBF) was measured by the 133Xe intravenous injection method using a Cerbrograph (Novo), and gray matter flow (F1) and initial slope index (ISI) were calculated. The cerebrovascular reactivity to CO2 was estimated as the increase in F1 or ISI per unit increase in PaCO2 (delta F1/delta PaCO2 or delta ISI/delta PaCO2, respectively) during inhalation of 5% CO2 and as %increase in F1 or ISI per unit increase in PaCO2 (delta F1%/delta PaCO2 or delta ISI%/delta PaCO2, respectively) during inhalation of 5% CO2. 1. CO2 reactivity in both groups. delta F1/delta PaCO2 in the MI and MID groups were 3.2 +/- 1.4 ml/100 g/min/mmHg and 2.0 +/- 1.4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)","Aged;Aged, 80 and over;Carbon Dioxide;Cerebral Infarction/ physiopathology;Cerebrovascular Circulation/ drug effects;Dementia, Vascular/ physiopathology;Female;Humans;Male;Middle Aged","Takahashi, W.;Takagi, S.;Nagayama, M.;Shinohara, Y.",1992,Nov,,0,
942,Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis,"Multifractal analysis based on generalized concepts of fractals has been applied to evaluate biological tissues composed of complex structures. This type of analysis can provide a precise quantitative description of a broad range of heterogeneous phenomena. Previously, we applied multifractal analysis to describe heterogeneity in white matter signal fluctuation on T2-weighted MR images as a new method of texture analysis and established Deltaalpha as the most suitable index for evaluating white matter structural complexity (Takahashi et al. J. Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that pathophysiological processes occurring in deep white matter regions may be partly responsible for cognitive deterioration and dementia in elderly subjects. We carried out a multifractal analysis in a group of 36 healthy elderly subjects who showed no evidence of atherosclerotic risk factors to examine the microstructural changes of the deep white matter on T2-weighted MR images. We also performed conventional texture analysis, i.e., determined the standard deviation of signal intensity divided by mean signal intensity (SD/MSI) for comparison with multifractal analysis. Next, we examined the association between the findings of these two types of texture analysis and the ultrasonographically measured intima-media thickness (IMT) of the carotid arteries, a reliable indicator of early carotid atherosclerosis. The severity of carotid IMT was positively associated with Deltaalpha in the deep white matter region. In addition, this association remained significant after excluding 12 subjects with visually detectable deep white matter hyperintensities on MR images. However, there was no significant association between the severity of carotid IMT and SD/MSI. These results indicate the potential usefulness of applying multifractal analysis to conventional MR images as a new approach to detect the microstructural changes of apparently normal white matter during the early stages of atherosclerosis.","Aged;Algorithms;Atherosclerosis/ pathology;Blood Pressure/physiology;Blood Pressure Monitoring, Ambulatory;Body Mass Index;Brain/ pathology/ultrastructure;Carotid Arteries/pathology/ultrasonography;Cholesterol/blood;Female;Fractals;Humans;Image Processing, Computer-Assisted;Linear Models;Magnetic Resonance Imaging;Male;Reproducibility of Results;Risk Factors","Takahashi, T.;Murata, T.;Narita, K.;Hamada, T.;Kosaka, H.;Omori, M.;Takahashi, K.;Kimura, H.;Yoshida, H.;Wada, Y.",2006,Sep,10.1016/j.neuroimage.2006.04.218,0,
943,Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging,"Alzheimer disease (AD) is pathologically characterized by cortical atrophy. Changes in the white matter and their relation to the pathogenesis of AD remain to be studied. To quantitatively investigate the integrity and organization of white matter fiber tracts in patients with AD, we used diffusion tensor (DT) imaging to study the diffusion anisotropy of white matter regions. DT imaging was performed using a 3.0 Tesla magnetic resonance scanner in ten probable AD patients with no or only mild changes in the white matter in T2 weighted magnetic resonance imagings and ten group-matched controls. The values of fractional anisotropy were significantly lower in the temporal subcortical white matter, posterior part of the corpus callosum, and anterior and posterior cingulate bundles in patients with AD compared with controls. Possible relationships of these selective impairments in the white matter with pathological changes in the posterior cerebral cortices and hippocampus were discussed.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/pathology;Statistics, Nonparametric","Takahashi, S.;Yonezawa, H.;Takahashi, J.;Kudo, M.;Inoue, T.;Tohgi, H.",2002,Oct 25,,0,
944,Correlation of lesions in the hippocampal region noted on MR images with clinical features,"The purpose of our work was to compare the MR imaging findings of obvious hippocampal and/or juxtahippocampal lesions with corresponding clinical features. Magnetic resonance images of 63 patients with obvious lesions in the hippocampal and/or juxtahippocampal regions were reviewed and their findings were correlated with patients' clinical characteristics. Based on the MR and clinical findings, the patients were divided into four groups: (a) 26 patients with space occupying lesions or suspected vascular malformation frequently causing symptomatic temporal epilepsy; (b) 14 with hippocampal infarcts, which when left-sided or bilateral caused amnesia; (c) 11 with encephalitis and 5 with old temporal contusion usually accompanied by both amnesia and epilepsy; and (d) 7 with temporal atrophy and progressive dementia of subacute onset. Magnetic resonance imaging allows precise localization and evaluation of the clinical correlates of hippocampal and juxtahippocampal lesions, which frequently caused symptomatic temporal epilepsy and/or amnesic syndrome.","Adolescent;Adult;Aged;Brain Concussion/diagnosis;Brain Diseases/ diagnosis;Brain Neoplasms/diagnosis;Cerebral Infarction/diagnosis;Child;Child, Preschool;Dementia/diagnosis;Encephalitis/diagnosis;Epilepsy/diagnosis;Female;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Takahashi, S.;Higano, S.;Kurihara, N.;Mugikura, S.;Sakamoto, K.;Nomura, H.;Ikeda, H.",1997,,10.1007/s003300050151,0,
945,Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra: A comparison with conventional voxel-based morphometry,"BACKGROUND AND PURPOSE: DLB is recognized as the second major form of dementia in the elderly. The regional pattern of GM atrophy in DLB highly overlaps that in AD. The aim of this study was to identify the critical pattern of atrophy in DLB by using DARTEL, which provides improved registration accuracy compared with that of conventional VBM. MATERIALS AND METHODS: We evaluated 51 patients with probable AD, 43 patients with probable DLB, and 40 age-matched healthy controls. The pattern of GM atrophy in each group was compared by using conventional VBM and VBM-DARTEL. RESULTS: Regional patterns of atrophy identified by using conventional VBM differed significantly from those identified by using VBM-DARTEL. A decrease in GM volume in the MTLs in both AD and DLB was identified with VBM-DARTEL; the decrease was greater in patients with AD than in those with DLB. Comparisons with healthy controls revealed that the WM volume of the whole brain was preserved in patients with DLB. In contrast, a severe bilateral decrease in WM in the MTLs was detected in patients with AD. CONCLUSIONS: VBM-DARTEL provided more accurate results, and it enabled the identification of more localized morphologic alterations than did conventional VBM. Analysis of WM preservation in DLB could help to differentiate this condition from AD.","Aged;Algorithms;Alzheimer Disease/pathology;Atrophy;Diagnosis, Differential;Female;Follow-Up Studies;Humans;Leukoencephalopathies/ pathology;Lewy Body Disease/ pathology;Magnetic Resonance Imaging/ methods/ standards;Male;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Reproducibility of Results","Takahashi, R.;Ishii, K.;Miyamoto, N.;Yoshikawa, T.;Shimada, K.;Ohkawa, S.;Kakigi, T.;Yokoyama, K.",2010,Nov,,0,
946,Measurement of gray and white matter atrophy in dementia with Lewy bodies using diffeomorphic anatomic registration through exponentiated lie algebra: A comparison with conventional voxel-based morphometry,"BACKGROUND AND PURPOSE: DLB is recognized as the second major form of dementia in the elderly. The regional pattern of GM atrophy in DLB highly overlaps that in AD. The aim of this study was to identify the critical pattern of atrophy in DLB by using DARTEL, which provides improved registration accuracy compared with that of conventional VBM. MATERIALS AND METHODS: We evaluated 51 patients with probable AD, 43 patients with probable DLB, and 40 age-matched healthy controls. The pattern of GM atrophy in each group was compared by using conventional VBM and VBM-DARTEL. RESULTS: Regional patterns of atrophy identified by using conventional VBM differed significantly from those identified by using VBM-DARTEL. A decrease in GM volume in the MTLs in both AD and DLB was identified with VBM-DARTEL; the decrease was greater in patients with AD than in those with DLB. Comparisons with healthy controls revealed that the WM volume of the whole brain was preserved in patients with DLB. In contrast, a severe bilateral decrease in WM in the MTLs was detected in patients with AD. CONCLUSIONS: VBM-DARTEL provided more accurate results, and it enabled the identification of more localized morphologic alterations than did conventional VBM. Analysis of WM preservation in DLB could help to differentiate this condition from AD.","Algorithms;Alzheimer Disease [pathology];Atrophy;Diagnosis, Differential;Follow-Up Studies;Leukoencephalopathies [pathology];Lewy Body Disease [pathology];Magnetic Resonance Imaging [methods] [standards];Nerve Fibers, Myelinated [pathology];Neurons [pathology];Reproducibility of Results;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword]","Takahashi, R.;Ishii, K.;Miyamoto, N.;Yoshikawa, T.;Shimada, K.;Ohkawa, S.;Kakigi, T.;Yokoyama, K.",2010,,10.3174/ajnr.A2200,0,945
947,White matter lesions or Alzheimer's disease: Which contributes more to overactive bladder and incontinence in elderly adults with dementia?,,aged;Alzheimer disease;clinical article;disease severity;female;human;letter;male;Mini Mental State Examination;nuclear magnetic resonance imaging;overactive bladder;questionnaire;rating scale;scoring system;urinary frequency;urine incontinence;urodynamics;white matter lesion,"Takahashi, O.;Sakakibara, R.;Panicker, J.;Fowler, C. J.;Tateno, F.;Kishi, M.;Tsuyusaki, Y.;Yano, H.;Sugiyama, M.;Uchiyama, T.;Yamamoto, T.",2012,,,0,
948,[Augmentation therapy with cilostazol for the intractable geriatric major depressive disorder patients with deep white matter hyperintensities on T2-weighted brain MRI],"Several studies report that vascular lesions contribute to depression in late life, but whether vascular lesions contribute to depression or indeed result from depression is debatable. To address this question, we segregated mood disorder patients into late- and early-onset mood disorder groups (LOM and EOM, respectively) and compared the areas of high intensity on the subcortical MRI scans of the 2 groups. We found that the LOM group exhibited higher ratings than the EOM group; significant between-group differences were detected in the bilateral frontal areas and in the left parieto-occipital area. Our results suggest that vascular lesions in these areas are crucial for the development of late-onset mood disorders. Furthermore, treatment is often difficult in depressed patients with cerebrovascular lesions. Therefore, a new therapeutic approach that takes into account cerebrovascular factors is necessary. We concomitantly administered cilostazol with conventional antidepressants to patients with intractable geriatric major depressive disorder; of these patients, 2 showed improvements of their depressive symptoms. These findings suggest a potential efficacy of cilostazol as a novel drug for use in augmentation therapy for depressed patients with silent cerebrovascular disorder. Evidence that vascular disease is the underlying link between depression and dementia is strong. Therefore, further studies that include follow-up of such cases are necessary.",cilostazol;phosphodiesterase III inhibitor;tetrazole derivative;aged;article;brain;case report;cerebrovascular disease;female;human;major depression;male;middle aged;nuclear magnetic resonance imaging;pathology,"Takahashi, K.;Mikuni, M.",2012,,,0,
949,Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer's disease: high-resolution fast spin-echo T1-weighted imaging,"AIM: Neuronal degeneration in the locus coeruleus occurs in the early phase of Alzheimer's disease, similar to mild cognitive impairment. The locus coeruleus produces norepinephrine, a deficiency of which causes both memory disturbance and psychological symptoms. Thus, we evaluated signal alterations in the locus coeruleus of patients with Alzheimer's disease and mild cognitive impairment using a high-resolution fast spin-echo T1-weighted imaging. METHODS: A total of 22 patients with Alzheimer's disease, 47 patients with mild cognitive impairment and 26 healthy controls were prospectively examined by high-resolution fast spin-echo T1-weighted imaging at 3 Tesla. Signal intensities in the locus coeruleus were manually measured and expressed relative to those in the adjacent white matter structures as contrast ratios. RESULTS: Locus coeruleus contrast ratios were significantly reduced in patient groups with Alzheimer's disease, mild cognitive impairment that converted to Alzheimer's disease and mild cognitive impairment that did not convert to Alzheimer's disease (1.80-16.09% [median, 9.30%], 3.45-14.84% [median 6.87%] and 3.01-19.19% [median 7.72%], respectively) compared with the healthy control group (6.24-20.94% [median 14.35%]; P < 0.0001). The sensitivity and specificity for discriminating these diseases were 85.0% and 69.2%, respectively, which suggests that this measurement can be carried out reliably. There was no significant difference in the locus coeruleus contrast ratios among the Alzheimer's disease, mild cognitive impairment-converted and mild cognitive impairment-non-converted groups. CONCLUSIONS: High-resolution fast spin-echo T1-weighted imaging can show signal attenuation in the locus coeruleus of patients with Alzheimer's disease or with mild cognitive impairment whose pathology may or may not eventually convert to Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/diagnosis/psychology;Disease Progression;Echo-Planar Imaging/ methods;Female;Follow-Up Studies;Humans;Image Enhancement/ methods;Locus Coeruleus/ pathology;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/etiology/psychology;Neuropsychological Tests;Prospective Studies;Time Factors","Takahashi, J.;Shibata, T.;Sasaki, M.;Kudo, M.;Yanezawa, H.;Obara, S.;Kudo, K.;Ito, K.;Yamashita, F.;Terayama, Y.",2015,Mar,10.1111/ggi.12280,0,
950,Non-inflammatory cerebral amyloid angiopathy as a cause of rapidly progressive dementia: A case study,"A 77 year-old men developed a subacute-onset, rapidly progressive cognitive decline. After 6 months of evolution, he scored 6 on the Mini-Mental State Examination and had left hemiparesis and hemineglect. The patient died 11 months after the onset of cognitive symptoms. Brain MRI showed microhemorrhages on gradient-echo sequence and confluent areas of white matter hyperintensities on T2-weighted images. Brain biopsy revealed amyloid-beta peptide deposition in vessel walls, some of them surrounded by micro-bleeds. In this case report, we discuss the role of cerebral amyloid angiopathy (CAA) in cognitive decline, due to structural lesions associated with hemorrhages and infarcts, white matter lesions and co-morbidity of Alzheimer's disease, as well as the most recently described amyloid angiopathy-related inflammation.",cerebral amyloid angiopathy;dementia;vascular dementia,"Takada, L. T.;Camiz, P.;Grinberg, L. T.;Leite, C. D. C.",2009,Oct-Dec,,0,
951,Quantitative analysis of hemodynamic and metabolic changes in subcortical vascular dementia using simultaneous near-infrared spectroscopy and fMRI measurements,"Subcortical vascular dementia (SVD) is a form of vascular dementia from small vessel disease with white matter lesions and lacunes. We hypothesized that hemodynamic and metabolic changes in the cortex during a simple motor task may reflect the impaired neurovascular coupling in SVD. We used fMRI and near-infrared spectroscopy (NIRS) simultaneously, which together provided multiple hemodynamic responses as well as a robust estimation of the cerebral metabolic rate of oxygen (CMRO(2)). During the task periods, the oxy-hemoglobin, total-hemoglobin, blood oxygenation level-dependent (BOLD) response, cerebral blood flow (CBF), and CMRO(2) decreased statistically significantly in the primary motor and somatosensory cortices of SVD patients, whereas the oxygen extraction fraction increased when compared with controls. Notably, the flow-metabolism coupling ratio, n representing the ratio of oxygen supply to its utilization, showed a robust reduction in the SVD patient group (n(Control)=1.99 +/- 0.23; n(SVD)=1.08 +/- 0.24), which implies a loss of metabolic reserve. These results support the pathological small vessel compromise, including an increased vessel stiffness, impaired vascular reactivity, and impaired neurovascular coupling in SVD. In conclusion, simultaneous measurement by NIRS and fMRI can reveal various hemodynamic and metabolic changes and may be used for as an early detection or monitoring of SVD.","Aged;Blood Flow Velocity;Brain Mapping/*methods;*Cerebrovascular Circulation;Dementia, Vascular/*physiopathology;Female;Humans;Magnetic Resonance Imaging/*methods;Male;Motor Cortex/*physiopathology;Oxygen/*blood;Spectroscopy, Near-Infrared/*methods","Tak, S.;Yoon, S. J.;Jang, J.;Yoo, K.;Jeong, Y.;Ye, J. C.",2011,Mar 1,10.1016/j.neuroimage.2010.11.046,0,
952,"Primary antiphospholipid antibody syndrome presenting with encephalopathy, psychosis and seizures","Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events, miscarriages and thrombocytopenia with persistently positive antiphospholipid antibodies.1,2 APS may be isolated (primary APS) or associated to a connective tissue disease, most often systemic lupus erythematosus (SLE).1,2 APS usually affects young patients before the fifth decade3 with stroke being the commonest neurological manifestation.4 Various other neurological manifestations are being recognized in patients with APS including migraine, epilepsy, multi-infarct dementia and chorea.2 The pathological process underlying the neurological manifestations remains obscure.1,2 Herein we report a case of primary APSpresenting with a group of unusual neurological manifestations in a 68-year-old woman. © The Author(s), 2011. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav.",acenocoumarol;cardiolipin antibody;diazepam;enoxaparin;phenytoin;quetiapine;aged;anamnesis;antibody titer;antiphospholipid syndrome;article;brain disease;case report;clinical feature;female;human;laboratory test;neurologic examination;nuclear magnetic resonance imaging;priority journal;psychosis;seizure,"Taipa, R.;Santos, E.",2011,,,0,
953,Gliomatosis cerebri diagnostic challenge: Two case reports,"Background: Gliomatosis cerebri is a specific entity defined as a diffuse neoplastic glial cell infiltration of the brain, preserving the architecture of the normal surrounding tissues, involving more than 2 cerebral lobes. Clinical symptoms or radiologic features are nonspecific, and patients are often misdiagnosed with other neurologic diseases. Review Summary: Here, we report the diagnostic workup of 2 patients with gliomatosis cerebri, discussing the clinical, radiologic, and pathologic findings. Case 1: a 64-year-old woman who presented with an intracranial hypertension syndrome and had symmetrical white matter T2-weighted and fluid-attenuated inversion recovery hyperintensities pattern on magnetic resonance imaging; and case 2: a 54-year-old man with the diagnosis of multiple sclerosis for 8 years who presented with de novo cognitive impairment and focal deficits. Conclusions: This report highlights the difficulty of this differential diagnosis and the need of considering it also in the presence of a symmetrical pattern of white matter involvement. Cerebral biopsy remains crucial for the correct diagnosis and treatment approach. © 2011 by Lippincott Williams & Wilkins.",,"Taipa, R.;Da Silva, A. M.;Santos, E.;Pinto, P. S.;Melo-Pires, M.",2011,September,,0,
954,Cognitive alterations in non-demented CADASIL patients,"CADASIL is an inherited small-artery disease of the brain due to mutations of the Notch3 gene on chromosome 19. It is characterized by strokes, migraine with aura, and severe mood disturbances during mid adulthood and leads progressively to subcortical dementia. The precise onset of the cognitive decline in CADASIL remains unknown. We report here the cognitive evaluation of 8 non-demented symptomatic patients with CADASIL from 35 to 66 years of age. Altered performances were found in all subjects with the Wisconsin Card-Sorting Test (WCST), in 5/8 with the Trail-Making Test, and in 3/8 with copying of Rey's figure. Altered performances with codes and similarities of the WAIS-R, the Wechsler Memory Scale, Raven's Progressive Matrices, and the category and letter fluency task were observed less frequently (n < or = 2). The score obtained with the WCST was not significantly correlated with the severity of the white-matter or basal ganglia signal abnormalities at MRI examination. Our data show that: (1) symptomatic CADASIL patients, although non-demented, can present with a subtle cognitive impairment; (2) tasks involving the frontal lobes are found most frequently altered, and (3) this subtle cognitive deficit can develop in the absence of major vascular events and does not appear to be correlated with the severity of brain lesions as seen at MRI examination.",Adult;Aged;Brain/pathology;Cerebral Arteries/abnormalities/pathology;Cerebrovascular Disorders/congenital/pathology/*psychology;Cognition/*physiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests,"Taillia, H.;Chabriat, H.;Kurtz, A.;Verin, M.;Levy, C.;Vahedi, K.;Tournier-Lasserve, E.;Bousser, M. G.",1998,Mar-Apr,,0,
955,Simultaneous subcortical infarcts as initial manifestation of CADASIL,,Notch3 receptor;adult;article;bradyphrenia;brain infarction;CADASIL;case report;dysarthria;gene mutation;human;leukoencephalopathy;male;middle aged;nuclear magnetic resonance imaging,"Taieb, G.;Renard, D.;Castelnovo, G.",2015,,,0,
956,Quantitative measurement of blood-brain barrier permeability in human using dynamic contrast-enhanced MRI with fast T(1) mapping,"Breakdown of the blood-brain barrier (BBB), occurring in many neurological diseases, has been difficult to measure noninvasively in humans. Dynamic contrast-enhanced magnetic resonance imaging measures BBB permeability. However, important technical challenges remain and normative data from healthy humans is lacking. We report the implementation of a method for measuring BBB permeability, originally developed in animals, to estimate BBB permeability in both healthy subjects and patients with white matter pathology. Fast T (1) mapping was used to measure the leakage of contrast agent Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) from plasma into brain. A quarter of the standard Gd-DTPA dose for dynamic contrast-enhanced magnetic resonance imaging was found to give both sufficient contrast-to-noise and high T(1) sensitivity. The Patlak graphical approach was used to calculate the permeability from changes in 1/T(1). Permeability constants were compared with cerebrospinal fluid albumin index. The upper limit of the 95% confidence interval for white matter BBB permeability for normal subjects was 3 × 10(-4) L/g min. MRI measurements correlated strongly with levels of cerebrospinal fluid albumin in those subjects undergoing lumbar puncture. Dynamic contrast-enhanced magnetic resonance imaging with low dose Gd-DTPA and fast T(1) imaging is a sensitive method to measure subtle differences in BBB permeability in humans and may have advantages over techniques based purely on the measurement of pixel contrast changes. Copyright © 2010 Wiley-Liss, Inc.",,"Taheri, S.;Gasparovic, C.;Shah, N. J.;Rosenberg, G. A.",2011,April,,0,
957,Blood-brain barrier permeability abnormalities in vascular cognitive impairment,"BACKGROUND AND PURPOSE: Disruption of the blood-brain barrier has been proposed to be important in vascular cognitive impairment. Increased cerebrospinal fluid albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the blood-brain barrier permeability in patients with vascular cognitive impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to quantify blood-brain barrier permeability in vascular cognitive impairment. Method- We studied 60 patients with suspected vascular cognitive impairment. They had neurological and neuropsychological testing, permeability measurements with dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index. Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal fluid was obtained from 20 individuals undergoing spinal anesthesia for nonneurological problems. RESULTS: Thirty-six patients were classified as SIVD, 8 as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was significantly increased in the SIVD group compared with 20 control subjects. Permeabilities for the patients with vascular cognitive impairment measured by dynamic contrast-enhanced MRI were significantly increased over control subjects (P<0.05). Patient age did not correlate with either the blood-brain barrier permeability or albumin index. Highest albumin index values were seen in the SIVD group (P<0.05) and were significantly increased over multiple and lacunar infarcts. K(i) values were elevated over control subjects in SIVD but were similar to multiple and lacunar infarcts. CONCLUSIONS: There was abnormal permeability in white matter in patients with SIVD as shown by dynamic contrast-enhanced MRI and albumin index. Future studies will be needed to determine the relationship of blood-brain barrier damage and development of white matter hyperintensities.","Adult;Aged;Aged, 80 and over;Albumins/*metabolism;Blood-Brain Barrier/*metabolism/pathology;Brain/metabolism/pathology;Cognition Disorders/*metabolism/pathology/psychology;Dementia, Vascular/*metabolism/pathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neurologic Examination;Neuropsychological Tests;Permeability","Taheri, S.;Gasparovic, C.;Huisa, B. N.;Adair, J. C.;Edmonds, E.;Prestopnik, J.;Grossetete, M.;Shah, N. J.;Wills, J.;Qualls, C.;Rosenberg, G. A.",2011,Aug,10.1161/strokeaha.110.611731,0,
958,A case of interval form of carbon monoxide poisoning with a remarkable recovery,"A 69-year-old woman was admitted to our hospital due to an interval form of carbon monoxide (CO) poisoning one month after acute CO poisoning. On admission, she had disorientation, memory disturbance, apathy, masked face, muscle rigidity, bradykinesia and parkisonian gait. An MRI (FLAIR image) revealed high signal intensity lesions in the bilateral globus pallidus and the white matter of the frontal lobe. Hyperbaric oxygen (HBO) therapy at 2 atmospheres for 60 min was given every day, in addition to citicoline, levodopa/DCI and selegiline hydrochloride. Cognitive disturbance and parkinsonism gradually decreased, and abnormal signals in the bilateral globus pallidus and the cerebral white matter were attenuated after the treatment. Neuropsychiatrie abnormalities except for a slight gait disturbance disappeared one and a half month after starting the treatment. In addition to HBO therapy, administration of citicoline, lovodopa and selegiline may be useful in the case of the interval form of CO poisoning.",,"Taguchi, Y.;Takashima, S.;Inoue, H.",2005,May,,0,
959,Association between oral health and the risk of lacunar infarction in Japanese adults,"BACKGROUND: Poor oral health is associated with an increased risk of dementia in the elderly. One possible pathway linking these two phenomena is lacunar infarction, a potential cause of dementia. An association between poor oral health and an increased risk of ischaemic stroke has been recognised through the oral infection-inflammation pathway. However, little is known about whether poor oral health is associated with the progression of lacunar infarction. OBJECTIVE: We examined the association between variables related to oral health and lacunar infarction, as detected by magnetic resonance imaging (MRI). METHODS: A total of 110 subjects (52 men, 58 women), aged 27-76 years, who visited our periodontology clinic participated in this study. The subjects underwent dental radiography, periodontal examinations and brain MRI. One experienced specialist in cardiovascular disease and one experienced neurosurgeon determined the number of lacunar infarctions on brain MRI. Periodontologists performed clinical periodontal examinations. Variables related to oral health were determined from the radiographs by an oral radiologist. Information on the subjects' lifestyles and disease histories were obtained using a structured questionnaire and confirmed by clinical records. Adjacent categories logit regression analysis with backward elimination was used to determine variables associated with three groups based on the number of lacunar infarctions. RESULTS: Of the 110 subjects, 61 had lacunar infarctions. Nineteen had multiple (>/=7) lesions. Aging (p = 0.0004), increased time spent in physical activity per day (p = 0.042), the presence of hypertension (p = 0.006), the absence of hyperlipidaemia (p = 0.045), the presence of diabetes mellitus (p = 0.025) and low alveolar bone height (p = 0.026) were significantly associated with an increased number of lacunar infarctions in the final regression model. The significance of hyperlipidaemia and alveolar bone height disappeared in an unadjusted model. An increased pocket depth, which indicates current periodontal disease progression, tended to be associated with an increased number of lacunar infarctions (p = 0.058). This tendency did not disappear in an unadjusted model. CONCLUSION: Our results suggest that lacunar infarction may be associated with current periodontal disease in Japanese adults.","Adult;Age Factors;Aged;Asian Continental Ancestry Group;Dementia/etiology;Diabetes Complications/etiology;Female;Humans;Hypertension/complications;Japan/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Oral Health;Periodontal Diseases/complications;Risk Factors;Stroke, Lacunar/diagnosis/epidemiology/ etiology;Tooth Loss/complications","Taguchi, A.;Miki, M.;Muto, A.;Kubokawa, K.;Migita, K.;Higashi, Y.;Yoshinari, N.",2013,,10.1159/000353707,0,
960,A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia,"Background: Among hereditary leukodystrophies, a considerable number remain unclassified. Patient and results: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy with possible dominant inheritance. A 44-year-old man presented with cerebellar ataxia as the initial symptom, and later, dementia and hyperreflexia with ankle clonus developed. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The patient's mother and older brother also had cerebellar ataxia and dementia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurological symptoms of adult-onset. Our patient died of pneumonia 5 years after the onset of disease. The histopathological findings consisted mainly of patchily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regions, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. Conclusions: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophies. Copyright © 2001 Elsevier Science B.V.",adult;article;autosomal dominant inheritance;case report;cell vacuole;cerebellar ataxia;clinical feature;dementia;disease course;histopathology;human;leukodystrophy;male;nuclear magnetic resonance imaging;priority journal;white matter,"Tagawa, A.;Ono, S.;Inoue, K.;Hosoi, N.;Kaneda, K.;Suzuki, M.;Nagao, K.;Shimizu, N.",2001,,,0,
961,Computed tomographic findings in relation to event-related potentials during visual discrimination tasks in patients with multiple cerebral infarcts,"Event-related potentials were recorded for 29 patients with multiple cerebral infarcts (MCI) (mean age, 65.7 years) during visual discrimination tasks to clarify the relationship between computed tomographic findings (CT) and P300 component. P300 latency in patients with MCI was significantly longer than that of 15 age-matched normal subjects (mean age, 65.4 years), although no significant difference was found in P300 amplitude between the two groups. There was a significant negative correlation between P300 latency and mental status as determined by the Hasegawa's Dementia Scale. Significant correlation was also found between P300 latency and the degree of ventricular dilatation or severity of periventricular lucency (PVL) on CT scan. P300 latency was not significantly correlated with the number of infarcts. P300 latency in patients with MCI thus appears related to the severity of PVLs and degree of ventricular dilatation in addition to mental status.","Cerebral Ventriculography;Cognition/physiology;Dementia, Multi-Infarct/*physiopathology/radiography;Dilatation, Pathologic/radiography;Discrimination (Psychology)/*physiology;*Evoked Potentials, Visual;Humans;Psychological Tests;Reaction Time;Severity of Illness Index;*Tomography, X-Ray Computed","Tachibana, H.;Toda, K.;Sugita, M.;Konishi, K.;Matsunaga, I.",1991,Aug,,0,
962,Xenon contrast CT-CBF scanning of the brain differentiates normal age-related changes from multi-infarct dementia and senile dementia of Alzheimer type,"Local cerebral blood flow (LCBF) and partition coefficients (L lambda) were measured during inhalation of stable xenon gas with serial CT scanning among normal volunteers (N = 15), individuals with multi-infarct dementia (MID, N = 10), and persons with senile dementia of Alzheimer type (SDAT, N = 8). Mean gray matter flow values were reduced in both MID and SDAT. Age-related declines in LCBF values in normals were marked in frontal cortex and basal ganglia. LCBF values were decreased beyond normals in frontal and temporal cortices and thalamus in MID and SDAT, in basal ganglia only in MID. Unlike SDAT and age-matched normals, L lambda values were reduced in fronto-temporal cortex and thalamus in MID. Multifocal nature of lesions in MID was apparent. Coefficients of variation for LCBFs were greater in MID compared with SDAT and/or age-matched normals.","Age Factors;Aged;Alzheimer Disease/*radiography;*Cerebrovascular Circulation;Dementia/*radiography;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed;Xenon Radioisotopes","Tachibana, H.;Meyer, J. S.;Okayasu, H.;Shaw, T. G.;Kandula, P.;Rogers, R. L.",1984,Jul,,0,
963,Xenon contrast CT-CBF measurements in parkinsonism and normal aging,"Local cerebral blood flow (LCBF) and local tissue:blood partition, coefficient (L lambda) values were measured during CT scanning while patients with different types of Parkinson's syndrome (N = 14) inhaled a contrast mixture of 35-37 per cent stable xenon gas in oxygen. Single-compartment analysis fitted to infinity was used to calculate L lambda and LCBF values. Results were compared with results from normal age-matched volunteers (N = 24). Mean hemispheric (p less than 0.05) and subcortical (p less than 0.05) gray matter LCBF values were reduced in idiopathic Parkinson's disease (N = 11), compared to values from age-matched normals. Regionally, LCBF reductions included frontal (p less than 0.001), parietal cortex (p less than 0.05), caudate (p less than 0.05), lentiform nuclei (p less than 0.001) and thalamus (p less than 0.05) reductions. L lambda values were normal. Unilateral tremor and/or rigidity correlated directly with reduced LCBF in contralateral lentiform (p less than 0.01) and caudate (p less than 0.01) nuclei. In postencephalitic Parkinsonism (N = 1) LCBF reductions were diffuse, with normal L lambda values. In the akinetic form of Parkinsonism (N = 1) associated with lacunar infarcts, LCBF and L lambda reductions were patchy. In Parkinsonism following carbon monoxide poisoning (N = 1), LCBF values of gray and white matter were diffusely reduced and L lambda values were reduced in both pallidal regions. When dementia was present together with Parkinsonism (N = 3), LCBF reductions were more diffuse and severe. Dopaminergic deficiency correlated directly with reduced LCBF values, reflecting the severity of Parkinsonism.","Adult;Aged;*Aging;Brain/physiopathology;Carbon Monoxide Poisoning/physiopathology;Caudate Nucleus/blood supply/physiopathology;Cerebral Cortex/blood supply/physiopathology;*Cerebrovascular Circulation;Dementia/physiopathology;Dopamine/physiology;Female;Functional Laterality;Humans;Male;Middle Aged;Muscle Rigidity/physiopathology;Parkinson Disease/*physiopathology;Thalamus/blood supply/physiopathology;*Tomography, X-Ray Computed;Tremor/physiopathology;Xenon","Tachibana, H.;Meyer, J. S.;Kitagawa, Y.;Tanahashi, N.;Kandula, P.;Rogers, R. L.",1985,Jun,,0,
964,Periventricular lucencies on computed tomography in multiple cerebral infarcts: correlation with cerebral blood flow measurements,"Forty-nine patients with multiple cerebral infarcts with a mean age of 70.2 years were studied to elucidate the effect of periventricular lucencies (PVLs) on cerebral blood flow (CBF). Patients with multiple cerebral infarcts showed significantly lower mean cortical blood flow (F1) values compared to 15 age-matched normal subjects (p less than .01). The mean F1 values were most significantly decreased in severe group of PVLs and moderately decreased in moderate and mild groups (p less than .05 between severe and mild groups); however, no significant differences in mean F1 values were found between severe and moderate groups. Demented patients showed significantly lower F1 values compared to nondemented patients (p less than .001) and normal subjects (p less than .001). There was no significant difference in the degree of PVL between demented and nondemented groups. As well, the mean F1 values were not significantly correlated with either the number of infarcts or ventricular dilatation. These results suggest that PVLs on CT (especially in severe cases of PVLs) may have some role in the reduction of cortical blood flow in patients with multiple cerebral infarcts.","Aged;Aged, 80 and over;Cerebral Infarction/complications/physiopathology/*radiography;*Cerebral Ventriculography;*Cerebrovascular Circulation;Dementia/complications;Humans;Middle Aged;Reference Values;*Tomography, X-Ray Computed","Tachibana, H.;Kaku, T.;Takeda, M.;Tsuchiyama, M.;Toda, K.;Kawabata, K.;Nishimura, H.;Sugita, M.",1990,Aug,,0,
965,Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis,"BACKGROUND: TRACK-HD is a prospective observational study of Huntington's disease (HD) that examines disease progression in premanifest individuals carrying the mutant HTT gene and those with early stage disease. We report 12-month longitudinal changes, building on baseline findings. METHODS: we did a 12-month follow-up of patients recruited from the four TRACK-HD study sites in Canada, France, the Netherlands, and the UK. Participants were premanifest individuals (preHD) carrying the mutant HTT gene, patients with early HD, and controls matched by age and sex with the combined preHD and early HD groups. Data were collected by use of 3T MRI and clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Statistical analysis assessed annualised change with the use of linear regression models to estimate differences between groups. FINDINGS: 116 preHD individuals, 114 early HD patients, and 115 people in the control group completed follow-up. Four preHD individuals, nine early HD patients, and eight people in the control group did not complete the follow-up. A further nine participants, who completed follow-up assessments, were unable to undergo MRI. After adjustment for demographics, annualised rates of generalised and regional brain atrophy were higher in preHD and early HD groups than in controls. Whole-brain atrophy rates were 0.20% (95% CI 0.05-0.34; p=0.0071) per year higher in preHD participants and 0.60% (0.44-0.76; p<0.0001) in early HD patients, and caudate atrophy rates were 1.37% (0.99-1.75; p<0.0001) per year higher in preHD and 2.86% (2.34-3.39; p<0.0001) in early HD. Voxel-based morphometry revealed grey-matter and white-matter atrophy, even in subjects furthest from predicted disease onset. Quantitative imaging showed statistically significant associations with disease burden, an indicator of disease pathology, and total functional capacity, a widely-used clinical measure of disease severity. Relative to controls, decline in cognition and quantitative motor function was detectable in both pre- and early HD, as was deterioration in oculomotor function in early HD. INTERPRETATION: quantitative imaging showed the greatest differentiation across the spectrum of disease and functional measures of decline were sensitive in early HD, with cognitive and quantitative motor impairment also detectable in preHD. We show longitudinal change over 12 months in generalised and regional brain volume, cognition, and quantitative motor tasks in individuals many years from predicted disease onset and show the feasibility of obtaining quantifiable endpoints for future trials.","Adult;Aged;Atrophy/pathology;Brain/ pathology/ physiopathology;Brain Mapping;Canada;Case-Control Studies;Cognition Disorders/diagnosis/ etiology;Disease Progression;Female;France;Humans;Huntington Disease/ complications/genetics/ pathology;Imaging, Three-Dimensional/methods;International Cooperation;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Middle Aged;Movement/physiology;Nerve Tissue Proteins/genetics;Netherlands;Nuclear Proteins/genetics;Observation;Young Adult","Tabrizi, S. J.;Scahill, R. I.;Durr, A.;Roos, R. A.;Leavitt, B. R.;Jones, R.;Landwehrmeyer, G. B.;Fox, N. C.;Johnson, H.;Hicks, S. L.;Kennard, C.;Craufurd, D.;Frost, C.;Langbehn, D. R.;Reilmann, R.;Stout, J. C.",2011,Jan,10.1016/s1474-4422(10)70276-3,0,
966,Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: Analysis of 24 month observational data,"Background: TRACK-HD is a prospective observational biomarker study in premanifest and early Huntington's disease (HD). In this report we define a battery of potential outcome measures for therapeutic trials. Methods: We assessed longitudinal data collected at baseline, 12 months, and 24 months at sites in Leiden (Netherlands), London (UK), Paris (France), and Vancouver (Canada). Participants were individuals without HD but carrying the mutant HTT gene (ie, premanifest HD), patients with early HD, and healthy control individuals matched by age and sex to the combined HD groups. Data were collected with 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric assessments. We estimated adjusted, between-group differences in rates of change in these measures and concomitant longitudinal effect sizes. Findings: Longitudinal data were available for 116 control individuals, 117 premanifest gene carriers, and 116 participants with early HD. Significantly greater progressive grey-matter, white-matter, whole-brain, and regional atrophy was recorded in the premanifest and early",,"Tabrizi, S. J.;Reilmann, R.;Roos, R. A. C.;Durr, A.;Leavitt, B.;Owen, G.;Jones, R.;Johnson, H.;Craufurd, D.;Hicks, S. L.;Kennard, C.;Landwehrmeyer, B.;Stout, J. C.;Borowsky, B.;Scahill, R. I.;Frost, C.;Langbehn, D. R.",2012,January,,0,
967,Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data,"BACKGROUND: Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated HTT and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions. METHODS: This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD. FINDINGS: The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease. INTERPRETATION: We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.",Adolescent;Adult;Aged;Atrophy/diagnosis/pathology/physiopathology;Biomarkers/*analysis;Brain/pathology/*physiopathology;Cognition Disorders/diagnosis/etiology/physiopathology;Cohort Studies;Cross-Sectional Studies;Disease Progression;Early Diagnosis;Female;Genetic Predisposition to Disease/genetics;Genetic Testing;Heterozygote Detection/methods;Humans;Huntington Disease/*diagnosis/genetics/*physiopathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination/methods;Predictive Value of Tests;Reference Values;Young Adult,"Tabrizi, S. J.;Langbehn, D. R.;Leavitt, B. R.;Roos, R. A.;Durr, A.;Craufurd, D.;Kennard, C.;Hicks, S. L.;Fox, N. C.;Scahill, R. I.;Borowsky, B.;Tobin, A. J.;Rosas, H. D.;Johnson, H.;Reilmann, R.;Landwehrmeyer, B.;Stout, J. C.",2009,Sep,10.1016/s1474-4422(09)70170-x,0,
968,Physical Exercise with Music Reduces Gray and White Matter Loss in the Frontal Cortex of Elderly People: The Mihama-Kiho Scan Project,"Findings from previous studies suggest that physical exercise combined with cognitive training produces more positive effects on cognitive function in elderly people than physical exercise alone. However, the brain plasticity associated with these proposed benefits of combined therapy has not yet been investigated in elderly subjects. We hypothesized that the dual task group would experience greater benefits than the physical exercise alone and non-exercise control groups with regard to both cognitive function and brain plasticity. This study investigated the effect of physical exercise with musical accompaniment on structural brain changes in healthy elderly people. Fifty-one participants performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM), 61 participants performed the same exercise without music (Ex), and 32 participants made up the non-exercise group (Cont). After the 1-year intervention, visuospatial functioning of the ExM but not the Ex group was significantly better than that of the Cont group. Voxel-based morphometry analyses revealed that the ExM group showed greater right superior frontal gyrus volume and preserved volumes of the right anterior cingulate gyrus, left superior temporal gyrus, and insula. These results indicate that compared with exercise alone, physical exercise with music induces greater positive effects on cognitive function and leads to subtle neuroanatomical changes in the brains of elderly people. Therefore, physical exercise with music may be a beneficial intervention to delay age-related cognitive decline.",cognition;dementia;human aging;magnetic resonance imaging;voxel-based morphometry,"Tabei, K. I.;Satoh, M.;Ogawa, J. I.;Tokita, T.;Nakaguchi, N.;Nakao, K.;Kida, H.;Tomimoto, H.",2017,,,0,
969,Prediction of Cognitive Decline from White Matter Hyperintensity and Single-Photon Emission Computed Tomography in Alzheimer's Disease,"BACKGROUND: While several studies support an association of white matter hyperintensity (WMH) volume and regional cerebral blood flow (rCBF) with cognitive decline in Alzheimer's disease (AD), no reports have simultaneously considered the effects of both factors on cognitive decline. OBJECTIVE: The purpose of the present study was to compare WMH volume and rCBF in relation to cognitive function by developing a new software program to fuse magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) data. METHOD: We used MRI, SPECT, and neuropsychological data from 182 serial outpatients treated at the memory clinic of our hospital. RESULTS: Twenty-nine AD patients fulfilled the inclusion criteria (18 females, mean age: 73.1 +/- 7.9 years, mean Mini-Mental State Examination: 23.1 +/- 3.0). Analysis of variance revealed that posterior deep WMH (DWMH) volume was significantly larger than both anterior periventricular hyperintensity (PVH) and DWMH, and posterior PVH volumes. Multivariate regression analysis showed that increased volumes of the anterior PVH and the posterior DWMH and decreased rCBF of the parietal cortex negatively affected cognitive function. The other areas had no significant negative effects on cognitive function. CONCLUSION: Our findings show that the volume of the posterior WMH was significantly larger than that of other areas, and the increased posterior WMH volume and decreased rCBF of the parietal cortex negatively affected cognitive function. Therefore, the posterior WMH volume and the parietal rCBF are key parameters of cognitive decline in AD patients.",Alzheimer's disease;cognitive decline;dementia;neuropsychological test;single-photon emission computed tomography;white matter hyperintensity,"Tabei, K. I.;Kida, H.;Hosoya, T.;Satoh, M.;Tomimoto, H.",2017,,,0,
970,Amyloid beta protein deposition in brains from elderly subjects with leukoaraiosis,"We studied immunocytochemically with 2 amyloid beta protein (ABP) antisera brains from 5 non-demented elderly subjects with evidence of diffuse periventricular white matter hypodensity on computed tomography. In periventricular white matter of all brains we found ABP reactive deposits arranged around small vessels walls. Furthermore ABP reactive deposits, identical to those currently called diffuse plaques, were detected in neocortex in amount proportional to that of white matter deposits. We suggest that ABP microangiopathy and parenchymal deposition is responsible of white matter rarefaction in a subset of cases with a diffuse hypodensity on CT scan which has been called leukoaraiosis.","Aged;Amyloid beta-Peptides/*analysis;Brain/*pathology/radiography;Dementia/*pathology/radiography;Humans;Immunohistochemistry;Organ Specificity;Tomography, X-Ray Computed","Tabaton, M.;Caponnetto, C.;Mancardi, G.;Loeb, C.",1991,Dec,,0,
971,Carotid stenosis and the cognitive function,"While stroke is a known cause of a cognitive impairment, the relationship between a carotid artery stenosis and the cognitive function in individuals without a history of stroke is less clear. A number of risk factors for vascular disease are related to a cognitive impairment. Hypertension, diabetes mellitus, cigarette smoking, and dyslipidemia are also associated with an increased risk of carotid artery disease. Some studies have suggested that a stenosis of the internal carotid artery may be an independent risk factor for a cognitive impairment. A high-grade stenosis of the internal carotid artery may be associated with a cognitive impairment even without evidence of infarction on magnetic resonance imaging. On the other hand, it is fairly common that patients display a normal cognition despite severe carotid artery disease, highlighting the important role of an efficient collateral blood supply. The possible pathomechanisms of a cognitive impairment include silent embolization and hypoperfusion. Carotid endarterectomy or stenting may lead to a decline in the cognitive function in consequence of microembolic ischemia or intraprocedural hypoperfusion. Conversely, perfusion restoration could improve a cognitive dysfunction that might have occurred from a state of chronic hypoperfusion. It is unclear whether these complex interactions ultimately result in a net improvement or a deterioration of the cognitive function. The evidence available at present does not seem strong enough to include consideration of a loss of cognition as a factor in determining the balance of the risks and benefits of therapy for a carotid stenosis. © 2009 Elsevier B.V. All rights reserved.",,"Sztriha, L. K.;Nemeth, D.;Sefcsik, T.;Vecsei, L.",2009,15,,0,
972,L-2-hydroxyglutaric aciduria in two siblings,"Two Pakistani siblings with L-2-hydroxyglutaric aciduria are reported herein. A 6-year-old male and a 2-year-old female, born to consanguineous parents, had chronic slowly progressive neurodegenerative disorder with insidious onset after infancy. Mental regression and seizures were evident in both patients, whereas cerebellar dysfunction was the main motor handicap in the male and pyramidal symptoms were prominent in the female. Magnetic resonance imaging revealed bilateral symmetrical abnormal signal in the subcortical white matter, internal and external capsules, basal ganglia, and dentate nuclei. The underlying metabolic defect, which is likely inherited in an autosomal recessive mode, remains unknown in this disorder. © 2002 by Elsevier Science Inc. All rights reserved.",,"Sztriha, L.;Gururaj, A.;Vreken, P.;Nork, M.;Lestringant, G. G.",2002,August,,0,
973,Inflammatory cerebral amyloid angiopathy: The overlap of perivascular (PAN-like) with vasculitic (Aβ-related angiitis) form: An autopsy case,"Beside advanced age, cerebral amyloid angiopathy (CAA) and hypertension (HTA) are the two most important risk factors for haemorrhagic stroke. Inflammatory changes of amyloid-laden vessels have been reported only in rare sporadic CAA cases. We present the case of a 78-year-old woman with a history of hypertension, dementia and haemorrhagic stroke of the right frontal lobe 2 years before admission. She was admitted with recurrence of symptoms of transient aphasia and central, right-side facial paresis that occurred an hour before her arrival at the hospital. In the admission unit, she was only slightly confused, with no other neurological deficits. An urgent CT scan revealed a recent haemorrhagic stroke in the left frontal lobe. In an hour her condition suddenly deteriorated. After a generalized seizure she presented with right-side hemiparesis with signs of uncal herniation and remained unconscious. A control CT scan showed a large haemorrhagic expansion that comprised the whole left brain hemisphere with 2 cm midline shift. She died about 10 hours after the onset of symptoms. At autopsy chronic inflammation of the thyroid gland, bronchopneumonia, fibrous and fatty heart degeneration and kidney haemorrhagic infarcts were documented. Amyloid deposition and systemic immune disorders in the inner organs were not demonstrated. In neuropathological examination we diagnosed inflammatory form of CAA with coexistence (the overlap) of two, perivascular and vascular, subtypes of CAA-related inflammation.",amyloid protein;collagen fiber;fibrin;aphasia;article;autopsy;brain hemorrhage;brain hernia;cardiovascular inflammation;clinical feature;computer assisted tomography;dementia;disease classification;facial nerve paralysis;frontal lobe;hemiparesis;human;hypertension;left hemisphere;neuropathology;perivascular inflammation;vascular amyloidosis;vasculitis,"Szpak, G. M.;Lewandowska, E.;Śliwińska, A.;Stȩpień, T.;Tarka, S.;Mendel, T.;Rafałowska, J.",2011,,,0,
974,Adult schizophrenic-like variant of adrenoleukodystrophy,"A 35-year-old man died after 30 months following the onset of the disease. There was a history of changes in his mental condition, including disturbances of behavior as well as the evidence of progressing dementia. The patient revealed gait disturbances and finally became bed ridden. Bizarre behavior and changes of mood with concurrent growing irritability which predominated during the course of disease, may explain the initial diagnosis of schizophrenia. Then cerebellar and spastic movement disorders leading to paraparesis and sphincters disturbances developed. Clinical symptoms of adrenal failure were not found apart from episodes of arterial pressure fall. After two years a magnetic resonance imaging (MRI) revealed an extensive diffuse demyelinative process in white matter of cerebral and cerebellar hemispheres. Activity of lysosomal enzymes was normal. A general autopsy revealed atrophy of adrenal cortex and the presence of ballooned cells with striated cytoplasm in the reticular and fasciculate zones. Neuropathological examination revealed an extensive demyelination of white matter in cerebral and cerebellar hemispheres and of the long paths of the brain stem, corresponding to changes in MRI examination. Within demyelination areas damage of axons and diffuse cellular and fibrous gliosis were found as well as perivascular lymphocytic infiltrations with the presence of strong PAS (+) and Sudan (+) macrophages. Immunocytochemical reactions with HAM-56 and RCA1 in macrophages were positive. Electron microscopy examination revealed lamellar inclusions in cytoplasm of macrophages. Similar structures were present in the lysosomes of astrocytes. Morphological examination of adrenal glands as well as morphological and ultrastructural study of the brain allowed us to diagnose the cerebral form of adrenoleukodystrophy (ALD). Topography and character of the brain changes seems to be in keeping with a rare schizophrenic-like variant of ALD with progressive dementia. Abnormal plasma profile and increased VLCFA concentration in the patient's 13-year-old daughter confirm the ALD diagnosis.",,"Szpak, G. M.;Lewandowska, E.;Schmidt-Sidor, B.;Popow, J.;Kozłowski, P.;Lechowicz, W.;Kulczycki, J.;Zaremba, J.;Dymecki, J.",1996,1996,,0,
975,Specific APO E genotypes in combination with the ACE D/D or MTHFR 677TT mutation yield an independent genetic risk of leukoaraiosis,"OBJECTIVE: Ischaemic demyelination of the white matter of the brain is a frequent clinical entity. In the neuroimaging terms, it is referred to as leukoaraiosis. We earlier found that the co-occurrence of the homozygous methylenetetrahydrofolate reductase (MTHFR) 677TT and angiotensin-converting enzyme D/D (ACE D/D) genotypes yielded a highly significant moderate risk of leukoaraiosis. On the assumption of further genetic interactions, we have now investigated whether the different apolipoprotein E (APO E) genotypes, in pairwise combinations with the MTHFR 677TT or ACE D/D mutation, could lead to an increased risk of leukoaraiosis. MATERIAL AND METHODS: We analysed the occurrence of the APO E genotypes in pairwise combinations with the MTHFR 677TT or ACE D/D mutation in 315 consecutive Caucasian patients with leukoaraiosis. A total of 646 neuroimaging-free subjects acted as a control group. RESULTS: The APO E 2/2 and 2/3 or APO E 4/4 and 4/3 genotypes in combination with the MTHFR 677TT or ACE D/D mutation exhibited independent genetic risks of leukoaraiosis. CONCLUSION: The interactions of certain unfavourable genetic mutations can contribute to the evolution of leukoaraiosis.","Adult;Aged;Aged, 80 and over;Apolipoprotein E2;Apolipoprotein E3;Apolipoprotein E4;Apolipoproteins E/*genetics;Brain/pathology;*DNA Mutational Analysis;Dementia, Vascular/diagnosis/*genetics;Genetic Predisposition to Disease/*genetics;*Genotype;Homozygote;Humans;Magnetic Resonance Imaging;Methylenetetrahydrofolate Reductase (NADPH2)/*genetics;Middle Aged;Peptides/*genetics;Peptidyl-Dipeptidase A/*genetics;Polymorphism, Genetic/genetics;*Protein Interaction Mapping;Reference Values;Risk","Szolnoki, Z.;Somogyvari, F.;Kondacs, A.;Szabo, M.;Fodor, L.;Bene, J.;Melegh, B.",2004,Mar,,0,
976,"Assessment of degradation of the selected projectile, commissural and association brain fibers in patients with Alzheimer's disease on diffusion tensor MR imaging","BACKGROUND: Pathological examinations and the increasingly popular diffusion tensor imaging (DTI) show that in Alzheimer's disease (AD), the pathology involves not only the cortical and hippocampal structures, but also the white matter of the brain. DTI is a well recognized technique for evaluation of the integrity of white matter fibers. The aim of this study was to assess with the use of DTI some selected brain tracts in patients with AD, as well as to analyze the severity and distribution of the identified changes. MATERIAL/METHODS: Thirty-five patients with AD (mean age of 71.6 years, MMSE 17.6), and a control group of 15 healthy volunteers (mean age of 69.1 years, MMSE 29.8) were enrolled in the study. All patients were subjected to a thorough psychiatric examination and psychological tests. DTI examinations (TE 8500, TR 100) were performed using a 1.5T MR scanner. Fractional anisotropy (FA) measurements in the selected areas of interest (ROI) of the white matter fibers were performed under the control of color FA maps. The following fibers were evaluated - the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFO), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). RESULTS: There was a statistically significant decrease in FA in patients with AD, comparing to the control group. It was particularly strongly expressed in both CG (P<0.0001), followed by both ILF, right IFO, and left SLF. Less pronounced changes were found in GCC, SCC, and left IFO. In both PLICs and MCPs and in the right SLF, there was no significant change of FA. CONCLUSIONS: In Alzheimer's disease, there is a significant decrease in FA, which suggests degradation of the majority of the assessed white matter tracts. Distribution of these changes is not uniform. They involve the selected association fibers mainly and, to a lesser extent, the commissural fibers, while they are not found in the pyramidal tracts or medial cerebellar peduncles. Definitely, the most pronounced changes were found in the posterior cingula, the assessment of which (in the process of AD diagnostics) seems to be particularly promising.",,"Szewczyk, P.;Zimny, A.;Trypka, E.;Wojtynska, R.;Leszek, J.;Sasiadek, M.",2010,Apr,,0,
977,[Diffusion tensor imaging (DTI) in the differential diagnosis of normal pressure hydrocephalus and brain atrophy] Obrazowanie tensora dyfuzji (DTI) w diagnostyce roznicowej wodoglowia normotensyjnego i zaniku mozgu,"UNLABELLED: Clinical symptomatology of idiopathic normal pressure hydrocephalus, due to its overlap with dementias and neurodegenerative brain disorders, makes diagnosis challenging. As the neurological deficits are reversible there is a need for prompt and reliable noninvasive testing. The aim was to try to use and introduction into clinical practice of new non-invasive method--diffusion tensor imaging (DTI-Diffusion Tensor Imaging) discriminating patients classified as normal pressure hydrocephalus and patients diagnosed with brain atrophy. MATERIAL AND METHODS: Using magnetic resonance-diffusion tensor imaging, we examined white matter changes within the brains of patients diagnosed with idiopathic normal pressure hydrocephalus, cerebral atrophy and controls. Diffusion tensor brain images were obtained with 3Tesla and 1.5 Tesla MR-scanners. Fractional anisotropy brain maps were generated using a computer-automated method, and tract-based spatial statistics were then applied to compare the fractional anisotropy values in the clinical groups. The fractional anisotropy data were further investigated using region-of- interest analysis set within: fibre commissural the lateral ventricles (Fclv), forceps minor of corpus callosum (Fmin), cingulum (Cg), optic radiation (Orad), superior cerebellarpeduncle (Scp), substantia nigra (nucleus ruber) (Sn). RESULTS: Compared with the cerebral atrophy or control group, the FA values in the hydrocephalus group were significantly different in the posterior cingulate (Cg) and the forceps minor of the corpus callosum (Fmin). CONCLUSION: The pattern of white matter tracts changes in select brain regions distinguishes it from cerebral atrophy and control brains. Our pilot study adds to the body of knowledge advancing the understanding of the white matter pathology of idiopathic normal- pressure hydrocephalus.","Adult;Aged;Atrophy/diagnosis;Brain/ pathology;Cerebellum/pathology;Corpus Callosum/ pathology;Diagnosis, Differential;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Hydrocephalus, Normal Pressure/ diagnosis;Lateral Ventricles/pathology;Male;Middle Aged;Neurodegenerative Diseases/ diagnosis;Pilot Projects;Substantia Nigra/pathology;White Matter/ pathology","Szczepek, E.;Czerwosz, L.;Szary, C.;Czernicki, Z.",2014,Oct,,0,
978,Diffusion tensor imaging (DTI) in the differential diagnosis of normal pressure hydrocephalus and brain atrophy,"Clinical symptomatology of idiopathic normal pressure hydrocephalus, due to its overlap with dementias and neurodegenerative brain disorders, makes diagnosis challenging. As the neurological deficits are reversible there is a need for prompt and reliable noninvasive testing. The aim was to try to use and introduction into clinical practice of new non-invasive method--diffusion tensor imaging (DTI-Diffusion Tensor Imaging) discriminating patients classified as normal pressure hydrocephalus and patients diagnosed with brain atrophy. MATERIAL AND METHODS: Using magnetic resonance-diffusion tensor imaging, we examined white matter changes within the brains of patients diagnosed with idiopathic normal pressure hydrocephalus, cerebral atrophy and controls. Diffusion tensor brain images were obtained with 3Tesla and 1.5 Tesla MR-scanners. Fractional anisotropy brain maps were generated using a computer-automated method, and tract-based spatial statistics were then applied to compare the fractional anisotropy values in the clinical groups. The fractional anisotropy data were further investigated using region-of- interest analysis set within: fibre commissural the lateral ventricles (Fclv), forceps minor of corpus callosum (Fmin), cingulum (Cg), optic radiation (Orad), superior cerebellarpeduncle (Scp), substantia nigra (nucleus ruber) (Sn). RESULTS: Compared with the cerebral atrophy or control group, the FA values in the hydrocephalus group were significantly different in the posterior cingulate (Cg) and the forceps minor of the corpus callosum (Fmin). CONCLUSION: The pattern of white matter tracts changes in select brain regions distinguishes it from cerebral atrophy and control brains. Our pilot study adds to the body of knowledge advancing the understanding of the white matter pathology of idiopathic normal- pressure hydrocephalus.","Adult;Aged;Atrophy/diagnosis;Brain/ pathology;Cerebellum/pathology;Corpus Callosum/ pathology;Diagnosis, Differential;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Hydrocephalus, Normal Pressure/ diagnosis;Lateral Ventricles/pathology;Male;Middle Aged;Neurodegenerative Diseases/ diagnosis;Pilot Projects;Substantia Nigra/pathology;White Matter/ pathology","Szczepek, E.;Czerwosz, L.;Szary, C.;Czernicki, Z.",2014,Oct,,0,
979,Screening of vascular cognitive impairment on a Hungarian cohort,"Cerebrovascular disease is a major public health problem in Eastern European countries. A Hungarian post-stroke population was examined to estimate the rate of dementia, the risk factors for cognitive impairment, and the applicability of a recently established Canadian diagnostic checklist in this cohort. Chronic cerebrovascular outpatients were screened for cognitive impairment with a combined checklist: the Diagnostic Checklist for Vascular Dementia established by the Consortium of Canadian Centres for Clinical Cognitive Research using the Mini Mental State Examination instead of the detailed neuropsychological part of the Checklist. Of the 247 consecutive patients at a cerebrovascular outpatient unit, 176 had cerebrovascular disorder diagnosed either by computed tomography (CT; n=126) or by the clinical signs. Of these, 15% were cognitively impaired and 5% fulfilled the criteria of dementia. The mean age of the patients with cognitive impairment was significantly higher than that of patients with normal cognition (68.2+/-10.2 and 60.5+/-10.5 years, P<0.001). The Barthel index was significantly lower in the cognitively affected group than in non-affected patients (92.4+/-16.0 and 97.1+/-8.7, P=0.027). Diabetes and more than two subcortical infarcts on CT or magnetic resonance imaging were more frequent in patients with cognitive loss (P=0.043 and P=0.013, respectively). Cognitive performance was also influenced by the level of education. Higher age, diabetes, motor deficits, and multiple subcortical infarcts are risk factors for cognitive impairment after stroke. The combined checklist appears to be a practical screening test for cognitive impairment in patients with chronic cerebrovascular diseases.","Age Distribution;Aged;Analysis of Variance;Cerebrovascular Disorders/complications/ diagnosis/ epidemiology;Cognition Disorders/ diagnosis/ epidemiology/etiology;Comorbidity;Demography;Diabetes Complications;Female;Humans;Hungary/epidemiology;Magnetic Resonance Imaging;Male;Mass Screening/ statistics & numerical data;Middle Aged;Predictive Value of Tests;Prevalence;Psychiatric Status Rating Scales/ standards;Risk Factors;Tomography, X-Ray Computed","Szatmari, S.;Fekete, I.;Csiba, L.;Kollar, J.;Sikula, J.;Bereczki, D.",1999,Feb,10.1046/j.1440-1819.1999.00468.x,0,
980,Does an increase in sulcal or ventricular fluid predict where brain tissue is lost?,"Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.","Adult;Aged;Aged, 80 and over;Alcoholism/pathology;Alzheimer Disease/pathology;Brain/ pathology;Brain Diseases/diagnosis/ pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Cerebrospinal Fluid;Female;HIV Infections/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Schizophrenia/pathology","Symonds, L. L.;Archibald, S. L.;Grant, I.;Zisook, S.;Jernigan, T. L.",1999,Oct,,0,
981,The sensitivity of the Mini-Mental State Exam in the white matter dementia of multiple sclerosis,"Fifty-six patients diagnosed with definite multiple sclerosis (MS) according to Poser criteria were administered the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. Extent of cerebral lesion involvement was determined by quantitative magnetic resonance imaging (MRI) ratings. The MMSE correlated with overall levels of physical disability, but did not correlate with total lesion area on MRI. Sensitivity of the MMSE to the subcortical dementia of MS was low (28%) when performance on the neuropsychological testing battery was used as the criterion. Impairment on tests of memory, speed of information processing, abstract reasoning, naming/verbal fluency, as well as visuoperceptual organization, were correlated highly with total lesion area on MRI. The low sensitivity of the MMSE to cognitive impairment in MS is discussed in terms of its item composition and the characteristic pattern of deficits found in MS.",Adult;Brain/pathology;Dementia/ diagnosis/psychology;Disability Evaluation;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule/ statistics & numerical data;Multiple Sclerosis/ diagnosis/psychology;Neurologic Examination/statistics & numerical data;Neuropsychological Tests/statistics & numerical data;Psychometrics,"Swirsky-Sacchetti, T.;Field, H. L.;Mitchell, D. R.;Seward, J.;Lublin, F. D.;Knobler, R. L.;Gonzalez, C. F.",1992,Nov,,0,
982,Autosomal dominant subcortical gliosis presenting as frontotemporal dementia,"OBJECTIVE:: To describe a multigenerational kindred with a frontotemporal dementia clinical syndrome (FTDS), extensive subcortical gliosis pathology, and autosomal dominant genetics. METHODS:: Clinical, imaging, and pathologic evaluations of multiple family members. RESULTS:: Symptom onset commonly occurred in the fifth or sixth decade, although some kindred members did not develop obvious symptoms until their eighth decade. White matter changes were prominent on both MRI and CT imaging. Results from six brain autopsy evaluations showed consistent but varying degrees of pathology that, while unique, share some histologic similarities with leukodystrophies. These brains were notably devoid of both tau- and ubiquitin-containing inclusions. CONCLUSIONS:: Subcortical gliosis in this kindred arises from mutation of a novel gene or else represents a unique frontotemporal dementia clinical syndrome variant caused by mutation of an already known gene. Clinical relevance and research implications are discussed. Copyright © 2009 by AAN Enterprises, Inc.",,"Swerdlow, R. H.;Miller, B. B.;Lopes, M. B. S.;Mandell, J. W.;Wooten, G. F.;Damgaard, P.;Manning, C.;Fowler, M.;Brashear, H. R.",2009,20,,0,
983,Clock drawing testing and diffusion tensor imaging among vascular dementia versus Alzheimer's disease,Purpose: To assess the clock drawing testing (CDT) and diffusion tensor magnetic resonance imaging (DT-MRI) differences between probable Alzheimer's dementia (AD) and vascular dementia (VaD) and the CDT correlation with the,,"Sweed, H. S.;Abdul-Rahman, S. A.;Abdel-Aal, W. M.;Abdul-Rahman, L. A.",2012,November,,0,
984,Preliminary investigations on automatic segmentation methods for detection and volume calculation of brain tumor from MR images,"Combining image segmentation based on the statistical classification with geometric prior information is supposed to increase robustness and reproducibility. A probability density function is initialized and a spatial constraint is defined which prevent segmentation that is not a part of the model. The goal of this work is a high quality image segmentation of healthy tissue and a precise delineation of tumor boundaries from multiple slices of MRI data. In this paper, algorithms like K-means, Watershed and Expectation Maximization algorithms are used for the investigation and the results of all the segmentations are compared. Based on the results, a common consensus on the robustness of each method is discussed. The Watershed segmentation and the Atlas are combined through markers and this has been applied in the Gray/White matter segmentation in MR images. A previous probability criterion is to be used for its calculation. These methods act as an aid in the early detection of many neurological disorders like Brain tumor, Paralysis, Alzheimer’s disease, etc. They also handle types of pathology, space occupying mass tumors, and infiltrating changes like edema aiding as a new technique for clinical routine for use in planning and monitoring in neurosurgery, radiology and radio-oncology. These methods can be enhanced to delineate tumor from surrounding tissues like edema aiding in image guided surgery. Both the off-line data and live patient data are used for the analysis. Testing of different algorithms for their robustness in segmenting the brain images are carried out using the image processing tool (IPT) of MATLAB.",gadolinium;algorithm;article;brain tumor;cluster analysis;edema;gray matter;human;image processing;image quality;image segmentation;monitoring;neurosurgery;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;radiology;treatment planning;white matter,"Swathi, K.;Balasubramanian, K.",2016,,,0,
985,Independent cognitive effects of atrophy and diffuse subcortical and thalamico-cortical cerebrovascular disease in dementia,"BACKGROUND AND PURPOSE: Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD. METHODS: Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility. RESULTS: A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures. CONCLUSIONS: These data support the hypothesis that the thalamico-cortical network subserves both short-term and working memory. The findings also suggest that each type of pathology (atrophy, small vessel disease, and strategic infarcts) contribute independently to the pattern of cognitive disabilities associated with dementia. Particular attention to cerebrovascular disease in deep white or gray matter structures of the thalamico-cortical system is certainly warranted.","Aged;Aged, 80 and over;Atrophy;Brain/*pathology;Cerebral Cortex/*blood supply;Cerebral Infarction/diagnosis/psychology;Cognition Disorders/diagnosis/*etiology;Dementia, Vascular/*diagnosis/psychology;Factor Analysis, Statistical;Female;Humans;*Magnetic Resonance Imaging;Male;Memory;Mental Processes;Middle Aged;Neuropsychological Tests;Severity of Illness Index;Thalamus/*blood supply","Swartz, R. H.;Stuss, D. T.;Gao, F.;Black, S. E.",2008,Mar,10.1161/strokeaha.107.491936,0,
986,Strategic involvement of cholinergic pathways and executive dysfunction: Does location of white matter signal hyperintensities matter?,"Cholinergic therapies have proven efficacious in the treatment of Alzheimer's disease, and recently in vascular and mixed dementia. We set out to evaluate the impact of putative cerebrovascular lesions involving cholinergic pathways in patients with cognitive impairment. White matter signal hyperintensities on magnetic resonance imaging involving cholinergic projections were classified according to a three-point rating scale for 171 individuals with cognitive impairment and 34 normal elderly controls. Medial temporal lobe width was measured, and a neuropsychological test battery was administered. Moderate or severe involvement of cholinergic pathways by white matter signal hyperintensities were identified in 60% of subjects with probable vascular dementia, 30% of subjects with possible/probable Alzheimer's disease, and 40% of subjects with cognitive impairment but no dementia. All control subjects were found to have minimal cholinergic pathway involvement. Medial temporal lobe width and signal hyperintensities on magnetic resonance imaging affecting cholinergic pathways were inversely related. Individuals with moderate and severe involvement of cholinergic pathways by white matter signal hyperintensities had greater impairment of executive function and visuospatial attention, despite equivalent degrees of global impairment and memory dysfunction when compared to those with minimal cholinergic pathway involvement. This is the first study to suggest that cerebrovascular disease may directly affect cholinergic projections and may exacerbate pre-existing cholinergic deficits of a degenerative nature, especially in probable Alzheimer's disease. Cerebrovascular compromise of cholinergic white matter projections may therefore be relevant in understanding the effects of cholinergic therapies.",,"Swartz, R. H.;Sahlas, D. J.;Black, S. E.",2003,Jan,10.1053/jscd.2003.5,0,
987,Cognitive impairment in dementia: correlations with atrophy and cerebrovascular disease quantified by magnetic resonance imaging,"This project assessed the contributions of atrophy and cerebrovascular disease (CVD) to cognitive impairment in dementia. Ten individuals with clinically diagnosed pure VaD were age-, sex-, and education-matched to individuals with AD. All participants underwent neuropsychological testing and MRI which were processed to generate quantitative indices of atrophy and CVD. A linear regression, including thalamic lesion and vCSF volumes, predicted cognitive status (R2 = .74; p < .0005). Three VaD subgroups were identified: thalamic lesion (n = 4), hippocampal infarcts (n = 3), and other (n = 3). In participants without thalamic lesion, vCSF predicted general cognition (R2 = .48), hippocampal atrophy predicted memory impairment (R2 = .33), and white matter lesions predicted executive dysfunction (R2 = .48). Both atrophy and CVD burden correlated highly with cognitive impairment and should be simultaneously assessed in studies of brain-behaviour relations in dementia.",,"Swartz, R. H.;Black, S. E.;Sela, G.;Bronskill, M. J.",2002,Jul,,0,
988,"Utility of simultaneous brain, CSF and hyperintensity quantification in dementia","Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/psychology;Brain/*pathology;Brain Damage, Chronic/*diagnosis/psychology;Brain Mapping;Cerebrospinal Fluid/*physiology;Dementia, Vascular/*diagnosis/psychology;Female;Humans;*Image Processing, Computer-Assisted;*Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Reference Values","Swartz, R. H.;Black, S. E.;Feinstein, A.;Rockel, C.;Sela, G.;Gao, F. Q.;Caldwell, C. B.;Bronskill, M. J.",2002,Nov 30,,0,
989,Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease,"Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.","0 (Aldehydes);0 (Biomarkers);0 (Lipid Peroxides);27415-26-5 (8-epi-prostaglandin F2alpha);B7IN85G1HY (Dinoprost);K1CVM13F96 (4-hydroxy-2-nonenal);Aged;Aged, 80 and over;Aldehydes/blood;Alzheimer Disease/complications;Biomarkers/blood;Cerebral Small Vessel Diseases/ diagnosis/diagnostic imaging/ etiology;Cohort Studies;Cross-Sectional Studies;Dinoprost/analogs & derivatives/blood;Female;Humans;Hypertension/complications;Lipid Peroxidation;Lipid Peroxides/blood;Magnetic Resonance Imaging;Male;Middle Aged;Oxidative Stress;Risk Factors;White Matter/diagnostic imaging;Cerebrovascular disease;Small vessel disease;White matter hyperintensities","Swardfager, W.;Yu, D.;Scola, G.;Cogo-Moreira, H.;Chan, P.;Zou, Y.;Herrmann, N.;Lanctot, K. L.;Ramirez, J.;Gao, F.;Masellis, M.;Swartz, R. H.;Sahlas, D. J.;Chan, P. C.;Ojeda-Lopez, C.;Milan-Tomas, A.;Pettersen, J. A.;Andreazza, A. C.;Black, S. E.",2017,Nov,,0,
990,Peripheral inflammatory markers indicate microstructural damage within periventricular white matter hyperintensities in Alzheimer's disease: A preliminary report,"INTRODUCTION: White matter hyperintensities (WMH) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. METHODS: Inflammatory markers were assayed in 54 elderly participants (n = 16 with AD). Periventricular WMH were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. RESULTS: Mean FA within periventricular WMH was associated with an inflammatory factor consisting of interleukin (IL)-1beta, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (rho = -0.703, P = .002) but not in healthy elderly (rho = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (rho = 0.425, P = .008) but not in patients with AD (rho = 0.174, P = .520). DISCUSSION: Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.",Alzheimer's disease;Cerebrovascular disease;Confirmatory factor analysis;Cytokine;Diffusion tensor imaging;Inflammation;Microstructure;Small vessel disease;White matter disease,"Swardfager, W.;Yu, D.;Ramirez, J.;Cogo-Moreira, H.;Szilagyi, G.;Holmes, M. F.;Scott, C. J.;Scola, G.;Chan, P. C.;Chen, J.;Chan, P.;Sahlas, D. J.;Herrmann, N.;Lanctot, K. L.;Andreazza, A. C.;Pettersen, J. A.;Black, S. E.",2017,,,0,
991,The effect of white matter hyperintensities on verbal memory: Mediation by temporal lobe atrophy,"OBJECTIVE: To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias. METHODS: We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning. RESULTS: In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [-0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific sign of AD. CONCLUSIONS: Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy.",,"Swardfager, W.;Cogo-Moreira, H.;Masellis, M.;Ramirez, J.;Herrmann, N.;Edwards, J. D.;Saleem, M.;Chan, P.;Yu, D.;Nestor, S. M.;Scott, C. J. M.;Holmes, M. F.;Sahlas, D. J.;Kiss, A.;Oh, P. I.;Strother, S. C.;Gao, F.;Stefanovic, B.;Keith, J.;Symons, S.;Swartz, R. H.;Lanctot, K. L.;Stuss, D. T.;Black, S. E.",2018,Jan 26,,0,
992,Discriminating power of the Hachinski Ischaemic Score in a geriatric population with mild dementia,"The Hachinski Ischaemic Score (HIS) is used to clinically discriminate multi-infarct dementia (MID) and primary degenerative dementia (PDD). The present study aims to evaluate the discriminating power of the individual HIS items in a geriatric population with mild dementia. The 13 HIS items were studied in 93 demented subjects with no evidence of infarction, a single cortical infarct or multiple cortical infarcts on CT brain scan. The item 'hypertension' was a poor discriminator between PDD and MID in this elderly population; however, the remaining unambiguous items 'abrupt onset', 'neurological signs', 'neurological symptoms', 'history of stroke' and 'atherosclerosis' were useful discriminators. We found that five of the least discriminating items diverged from the aspects of MID that they were originally intended to address and were, therefore, particularly ambiguous. In order to improve the discriminating power of these items and the HIS as a whole, we recommend dividing the 13 items into four categories, 'evidence of delirium', 'evidence of focal deficits', 'evidence of vascular pathology' and 'abrupt onset', to minimize any problems with interpretation of the more ambiguous items.",acute disease;adult;aged;article;atherosclerosis;brain ischemia;cerebrovascular disease;computer assisted tomography;controlled study;degenerative disease;delirium;dementia;diagnostic accuracy;female;focal epilepsy;human;hypertension;major clinical study;male;multiinfarct dementia;neurologic disease;scoring system;cerebrovascular accident,"Swanwick, G. R. J.;Coen, R. F.;Lawlor, B. A.;O'Mahony, D.;Walsh, J. B.;Coakley, D.",1995,,,0,
993,Magnetic resonance imaging in cerebrotendinous xanthomatosis,"In a patient with cerebrotendinous xanthomatosis, magnetic resonance imaging (MRI) revealed findings on demyelination in the cerebral white matter, which was also hypodense on CT. The MRI abnormality seemed to be clinically significant in this patient with progressive dementia and abnormal gait.",,"Swanson, P. D.;Cromwell, L. D.",1986,1986,,0,
994,Progressive dementia and leucoencephalopathy as the initial presentation of late onset hereditary cystatin-C amyloidosis. Clinicopathological presentation of two cases,"Hereditary Cystatin-C Amyloidosis (HCCA) is a genetic disorder in Icelandic families in which a defective cystatin-C amyloid protein is deposited in the walls of small and middle sized arteries. Cerebral vessels are most affected, resulting in recurrent cerebral hemorrhages and infarctions, usually with onset of clinical symptoms in the twenties or thirties and a rapidly deteriorating clinical course. The disease can be diagnosed by a skin biopsy in symptomatic patients. We report two patients (father and daughter) who did not have a known family history of the disorder and presented late in life with a progressive dementia, associated with cerebral hemorrhages in the younger patient, Cerebral MRI and CT scans of this patient showed extensive leukoencephalopathic changes. Brain tissue samples from both patients showed immunohistochemical reaction to cystatin-C in small and medium-sized cerebral arteries and extensive cortical and white matter microinfarctions. The amyloid changes were less severe in the older patient and a colocation of P-amyloid protein and cystatin-C was observed in addition to neurofibrillary tangles and senile plaques. Subcortical and cortical infarctions were also observed. HCCA may present late in life with progressive dementia as the only clinical manifestation, reflecting a multi-infarct syndrome secondary to the amyloidosis, A coexpression of cystatin-C and beta protein may occur as in other cerebral amyloid disorders, probably as age-specific changes.",cystatin C;adult;aged;amyloidosis;article;case report;computer assisted tomography;dementia;female;heredity;human;human tissue;leukoencephalopathy;male;nuclear magnetic resonance;priority journal,"Sveinbjörnsdóttir, S.;Blöndal, H.;Gudmundsson, G.;Kjartansson, O.;Jónsdóttir, S.;Gudmundsson, G.",1996,,,0,
995,The effect of white matter hyperintensities on statistical analysis of diffusion tensor imaging in cognitively healthy elderly and prodromal Alzheimer's disease,"Diffusion tensor imaging (DTI) has been used to study microstructural white matter alterations in a variety of conditions including normal aging and Alzheimer's disease (AD). White matter hyperintensities (WMH) are common in cognitively healthy elderly as well as in AD and exhibit elevated mean diffusivity (MD) and reduced fractional anisotropy (FA). However, the effect of WMH on statistical analysis of DTI estimates has not been thoroughly studied. In the present study we address this in two ways. First, we investigate the effect of WMH on MD and FA in the dorsal and ventral cingulum, the superior longitudinal fasciculus, and the corticospinal tract, by comparing two matched groups of cognitively healthy elderly (n = 21 + 21) with unequal WMH load. Second, we assess the effects of adjusting for WMH load when comparing MD and FA in prodromal AD subjects (n = 83) to cognitively healthy elderly (n = 132) in the abovementioned white matter tracts. Results showed the WMH in cognitively healthy elderly to have a generally large effect on DTI estimates (Cohen's d = 0.63 to 1.27 for significant differences in MD and -1.06 to -0.69 for FA). These effect sizes were comparable to those of various neurological and psychiatric diseases (Cohen's d = 0.57 to 2.20 for differences in MD and -1.76 to -0.61 for FA). Adjusting for WMH when comparing DTI estimates in prodromal AD subjects to cognitively healthy elderly improved the explanatory power as well as the outcome of the analysis, indicating that some of the differences in MD and FA were largely driven by unequal WMH load between the groups rather than alterations in normal-appearing white matter (NAWM). Thus, our findings suggest that if the purpose of a study is to compare alterations in NAWM between two groups using DTI it may be necessary to adjust the statistical analysis for WMH.","0 (Amyloid beta-Peptides);0 (Peptide Fragments);0 (amyloid beta-protein (1-40));0 (amyloid beta-protein (1-42));Aged;Alzheimer Disease/cerebrospinal fluid/ diagnostic imaging/ physiopathology;Amyloid beta-Peptides/cerebrospinal fluid;Anisotropy;Case-Control Studies;Cognition;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Peptide Fragments/cerebrospinal fluid;Prodromal Symptoms;White Matter/ diagnostic imaging/metabolism","Svard, D.;Nilsson, M.;Lampinen, B.;Latt, J.;Sundgren, P. C.;Stomrud, E.;Minthon, L.;Hansson, O.;van Westen, D.",2017,,,0,
996,Clinical characteristics and pharmaceutical treatment of drug induced pleurothotonus (Pisa syndrome),"Long term administration of antipsychotics occasionally produces pleurothotonus (Pisa syndrome). We investigated the clinical characteristics of drug induced pleurothotonus (Pisa syndrome) in 7 male and 20 female patients with this syndrome. All patients had received long term exposure to various antipsychotics, except for one patient taking tricyclic antidepressants. The primary psychiatric disorders were diagnosed as schizophrenia in 17 patients, mood disorder in 2, mental retardation in 7, and multi infarct dementia in 1. The mean age ± S. E. M. of males and females were 40.3±7.2 years and 40.3±3.1 years, respectively. The age at onset of drug induced pleurothotonus ranged widely from 18 to 71 years old. The X ray CT revealed abnormal findings, i.e., frontal or diffuse cortical atrophy and ventricular dilatation, in 15 (60%) of 25 patients. Anticholinergic medication was effective in 9 (43%) of 21 times of the occurrences. Reduction or discontinuation in daily dose of the antipsychotics benefited all the patients who failed to respond to anticholinergics. No significances were noted between responded and non responded groups to anticholinergics, with respect to gender, age, primary psychiatric diagnosis, direction of trunk, accompanying extrapyramidal symptoms, or brain organic lesions. Our findings suggest that most cases of drug induced pleurothotonus possess clinical characteristics similar to those of tardive dystonia. An imbalance of dopamine acetylcholine interactions may be in part involved in the underlying mechanism of drug induced pleurothotonus, although more complex disturbances among dopamine, serotonin, noradrenaline and GABA should be considered for the development of drug induced pleurothotonus and tardive dystonia.",biperiden;chlorpromazine;fluphenazine;haloperidol;levomepromazine;nortriptyline;perphenazine;promethazine;tiapride;trihexyphenidyl;zotepine;adult;affective neurosis;article;brain atrophy;brain scintiscanning;brain ventricle dilatation;clinical article;clinical feature;female;human;intramuscular drug administration;long term care;male;mental deficiency;multiinfarct dementia;nuclear magnetic resonance imaging;oral drug administration;psychopharmacotherapy;schizophrenia;tardive dyskinesia,"Suzuki, T.;Hori, T.;Baba, A.;Abe, S.;Kurita, H.;Shiraishi, H.;Moroji, T.",1997,,,0,
997,Elevated Serum Uric Acid Levels Are Related to Cognitive Deterioration in an Elderly Japanese Population,"AIMS: The association between serum uric acid (UA) levels and cognitive function is controversial since UA can be a risk factor for cerebral ischemia as well as acting as a neuroprotective antioxidant. METHODS: We conducted a cross-sectional analysis of 228 elderly participants and examined neuropsychological test results, clinical data as well as brain magnetic resonance imaging data. PATIENTS: Overall, 64 participants were diagnosed with cognitive deterioration. To control for the effect of sex differences, 2 independent sets of single-variable and multivariate logistic regression analyses were performed with quartiles divided into non-sex-specific and sex-specific cutoff values for UA. RESULTS: In non-sex-specific quartiles, the participants in the highest quartiles of UA levels were found to be at a significantly higher risk of cognitive deterioration than those in the lowest quartiles. In sex-specific quartiles, the highest quartile showed an increased risk of cognitive deterioration, and a greater than fourfold increase in the risk in the highest quartiles was confirmed using multivariate regression models. However, no significant association was observed between serum UA levels and the presence of white matter lesions. CONCLUSIONS: Elevated serum UA levels were independently associated with cognitive deterioration. UA might have unknown adverse effects on cognitive function, other than causing vascular pathology.",Cognitive deterioration;Dementia;Mild cognitive impairment;Risk factor;Uric acid;White matter lesion,"Suzuki, K.;Koide, D.;Fujii, K.;Yamazaki, T.;Tsuji, S.;Iwata, A.",2016,Sep-Dec,,0,
998,Mutation of the Notch 3 gene in a Thai cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family,"The authors report the first Thai family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which the family members had a classical history of progressive vascular dementia. The proband was a 31-year old Thai male who presented with an acute stroke in the subcortical region. His past history revealed mental disturbance, including poor judgement and regressive behavior as well as mood changes for 1 year. He did not have a history of migraine or any other vascular risk factors except for a strong family history of ischemic stroke and progressive dementia. Magnetic resonance imaging demonstrated multiple small infarctions in the subcortical white matter of the bilateral frontal, parietal and occipital lobes with another small lesion in the pons. Genetic study demonstrated a Notch 3 mutation consisting of the substitution of a nucleotide at position 406 in exon 3 leading to the replacement of an Arginine by Cysteine at position 110 in the 2(nd) EGF motif, which is compatable with CADASIL.",,"Suwanwela, N.;Tangwongchai, S.;Srikiatkhachorn, A.;Phanthumchinda, K.",2003,1,,0,
999,"A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials","During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity. Placebo or a similar, gamma-aminobutyric acid (GABA)-ergic, sedative zopiclone has no such effect. The effect appears only several months after the injury, reflecting recent evidence in mice of substantial differences between the states of GABA receptors in acute and chronic repair phases of recovery. Zolpidem's good safety record and rapid absorption further indicate a need for more clinical trials. List of acronyms: BOLD, Blood-Oxygen-Level Dependent contrast imaging in MRI; CRS, Coma Recovery Scale; CRS-R, Coma Recovery Scale Revised; CSI, Cerebral State Index; CSM, Cerebral State Monitor; DOC, Disorder of Consciousness; EEG, Electro Encephalography; FDG-PET, FluoroDeoxyGlucose-Positron Emission Tomography; FTD, Frontotemporal dementia; GABA, Gamma-Aminobutyric Acid; MCS, Minimally Conscious State; M-EEG, Magneto-Encephalography; MRI, Magnetic Resonance Image; MSN, Median Spiny Neurones; PET, Positron Emission Tomography; PVS, Persistent Vegetative Sate; RLAC, Rancho Los Amigos Cognitive scores; SPECT, Single-photon emission computed tomography; TFES, Tinetti Falls Efficacy Scale; 99mTc HMPAO, Technetium hexamethylpropyleneamine oxime.",Zolpidem;brain damage;review;stroke,"Sutton, J. A.;Clauss, R. P.",2017,,,0,
1000,Susac's syndrome: 1975-2005 microangiopathy/autoimmune endotheliopathy,"Susac's syndrome (SS) consists of the clinical triad of encephalopathy, branch retinal artery occlusions (BRAO) and hearing loss. It is due to a microangiopathy affecting the precapillary arterioles of the brain, retina, and inner ear (cochlea and semicircular canals). Women are more commonly affected than men (3:1); the age of onset ranges from 9 to 58 years; but young women between the ages of 20 and 40 are most vulnerable. The encephalopathy is almost always accompanied by headache which may be the presenting feature. Multifocal neurological signs and symptoms, psychiatric disturbances, cognitive changes, memory loss, and confusion may rapidly progress to dementia. The MRI shows a distinctive white matter disturbance that always affects the corpus callosum. The central callosal fibers are particularly vulnerable and central callosal holes develop as the active lesions resolve. Linear defects (spokes) and rather large round lesions (snowballs) sometime dominate the MRI findings, which include cortical, deep gray (70%) and leptomeningeal involvement (33%). Frequently, the lesions enhance and may be evident on diffusion weighted imaging (DWI). The BRAO are best evaluated with fluorescein angiography, which may show the pathognomonic multifocal fluorescence. Gass plaques are frequently present and reflect endothelial damage. Brain biopsy shows microinfarction to be the basic pathology, but more recent pathological studies have shown endothelial changes that are typical for an antiendothelial cell injury syndrome. Elevated levels of Factor VIII and von Willebrand Factor Antigen reflect the endothelial perturbation. Despite extensive evaluations, a procoagulant state has never been demonstrated. SS is an autoimmune endotheliopathy that requires treatment with immunosuppressants: steroids, cyclophosphamide, and intravenous immunoglobulin, usually in combination. Aspirin is a useful adjunct. © 2007 Elsevier B.V. All rights reserved.",,"Susac, J. O.;Egan, R. A.;Rennebohm, R. M.;Lubow, M.",2007,15,,0,
1001,Proton magnetic resonance spectroscopy in mild cognitive impairment and Alzheimer's disease: a preliminary study,"BACKGROUND: Mild cognitive impairment (MCI) is recognized as a transitional clinical state between normal aging and Alzheimer's disease (AD) and has significant higher rate of progression to AD. OBJECTIVE: To compare the changes of metabolites between AD and MCI in specific locations of the brain by using Magnetic Resonance Spectroscopy (MRS). MATERIAL AND METHOD: MMSE-Thai 2002 and neuropsychological test were performed in 17 patients with memory problem, classified into AD and MCI (10, 7 patients respectively). All patients and three age-matched cognitively normal volunteers were examined with conventional MRI and MRS of the brain. Volumes of interest were located at both-sided frontal and parietal deep white matter. NAA/Cr, Cho/Cr and mI/Cr ratios of the patients were analyzed and statistically evaluated relative to cognitively normal volunteers. Statistical analysis was performed using Cohen's kappa coefficient and Kruskal-Wallis test. RESULTS: There was no statistically significant change in metabolites in all brain regions. For AD relative to cognitively normal volunteers, there were strong tendency toward statistically significant decreased NAA/Cr at the left frontal and left parietal regions (p = 0.043 each) and decreased Cho/Cr at the left frontal region (p = 0.028). CONCLUSION: The changes of the metabolite ratios of MCI were much closer to AD. Strong tendency toward statistically significant decreased NAA/Cr in the left cerebral hemisphere, predominantly parietal region and strong tendency toward statistically significant decreased Cho/Cr at the left frontal region were indicative of neurodegeneration and replacement by gliosis. MRS may be useful for predict a chance that cognitively normal people may convert to the AD.","Aged;Aged, 80 and over;Alzheimer Disease/*metabolism/*pathology;Aspartic Acid/analogs & derivatives/metabolism;Case-Control Studies;Choline/metabolism;Creatine/metabolism;Cross-Sectional Studies;Female;Humans;Inositol/metabolism;Magnetic Resonance Spectroscopy;Male;Middle Aged;Mild Cognitive Impairment/*metabolism/*pathology","Suriyajakryuththana, W.;Tuntiyatorn, L.;Teepprasarn, N.;Sukying, C.",2014,Apr,,0,
1002,"In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, 18F -FEPPA","Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.",,"Suridjan, I.;Pollock, B. G.;Verhoeff, N. P.;Voineskos, A. N.;Chow, T.;Rusjan, P. M.;Lobaugh, N. J.;Houle, S.;Mulsant, B. H.;Mizrahi, R.",2015,Dec,10.1038/mp.2015.1,0,
1003,Prevalence of Intracranial Atherosclerotic Stenosis Using High-Resolution Magnetic Resonance Angiography in the General Population: The Atherosclerosis Risk in Communities Study,"Background and Purpose - Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using high-resolution magnetic resonance angiography in a US cardiovascular cohort. Methods - The Atherosclerosis Risk in Communities (ARIC) study recruited participants from 4 US communities from 1987 to 1989. Using stratified sampling, we selected 1980 participants from visit 5 (2011-2013) for high-resolution 3T-magnetic resonance angiography. All images were analyzed in a centralized laboratory, and ICAS was graded as: no stenosis, <50% stenosis, 50% to 69% stenosis, 70% to 99% stenosis, and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6538 visit 5 participants) and also estimated the US prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS. Results - Subjects who had an adequate magnetic resonance angiography (n=1765) were aged 67 to 90 years, 41% were men, 70% were white, and 29% were black. ICAS was prevalent in 31% of participants and 9% had ICAS >50%. Estimated US prevalence of ICAS >50% for 65 to 90 years old was 8% for whites and 12% for blacks. Older age, black race, higher systolic blood pressure, and higher low-density lipoprotein cholesterol levels were associated with increased odds of ICAS, whereas higher levels of high-density lipoprotein cholesterol and use of cholesterol-lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS. Conclusions - The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population.",age;aged;article;atherosclerosis;Black person;body mass;cardiovascular risk;cerebrovascular accident;cholesterol blood level;cohort analysis;comorbidity;controlled study;cross sectional study;diabetes mellitus;disease association;female;heart infarction;high resolution magnetic resonance angiography;human;hypertension;intracranial atherosclerotic stenosis;lipoprotein blood level;magnetic resonance angiography;major clinical study;male;medical history;neuroimaging;occlusive cerebrovascular disease;prevalence;priority journal;race difference;randomized controlled trial;risk assessment;systolic blood pressure;triacylglycerol blood level;high density lipoprotein/ec [Endogenous Compound];high density lipoprotein cholesterol/ec [Endogenous Compound];hypocholesterolemic agent;low density lipoprotein cholesterol/ec [Endogenous Compound];triacylglycerol/ec [Endogenous Compound],"Suri, M. F. K.;Qiao, Y.;Ma, X.;Guallar, E.;Zhou, J.;Zhang, Y.;Liu, L.;Chu, H.;Qureshi, A. I.;Alonso, A.;Folsom, A. R.;Wasserman, B. A.",2016,,10.1161/STROKEAHA.115.011292,0,
1004,Intact limbic-prefrontal connections and reduced amygdala volumes in Parkinson's disease with mild depressive symptoms,"Background: Depression is very common in Parkinson's disease (PD). The neuropathological basis for this remains unclear; however, dysfunction in prefrontal and limbic regions may play a role. Methods: We examined non-demented PD patients with and without depression and healthy controls (n = 6 per group) for differences in limbic structures and connections between these structures and the prefrontal cortex. Depressed individuals were selected from a representative sample of 33 PD patients using scores from the 15 question Geriatric Depression Scale (GDS). Magnetic Resonance Diffusion Tensor Imaging (DTI) tractography was used to examine the structural integrity of the uncinate fasciculus (UF), a white matter tract that projects from the hippocampus, amygdala and temporal pole to the orbitofrontal cortex, and the corpus callosum. Integrity of the UF and corpus callosum was established through measures of mean diffusivity (MD), fractional anisotropy (FA) and tract length. A volumetric analysis of the hippocampal head, body and tail, as well as the amygdala was performed to determine whether volume differences in these structures in PD relate to depression. Results: The depressed PD group showed smaller amygdala volumes compared to healthy controls, but the groups did not differ on any other measure. Conclusions: The present study found intact limbic connectivity but suggests that amygdala atrophy may be present in Parkinson's disease with depression. Further work is needed to replicate these findings. © 2012.",,"Surdhar, I.;Gee, M.;Bouchard, T.;Coupland, N.;Malykhin, N.;Camicioli, R.",2012,August,,0,
1005,White matter alterations in neurodegenerative and vascular dementia,"Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer's disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer's disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia.",,"Supprian, T.;Kessler, H.;Retz, W.;Rösler, M.;Grunwald, I.;Reith, W.;Falkai, P.",2003,1,,0,
1006,Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise,"Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (P corrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.",adult;aged;Alzheimer Disease Assessment Scale;article;cognition;controlled study;dementia;female;follow up;functional connectivity;functional magnetic resonance imaging;hippocampus;human;major clinical study;male;mild cognitive impairment;neuroimaging;posterior cingulate;priority journal;resistance training,"Suo, C.;Singh, M. F.;Gates, N.;Wen, W.;Sachdev, P.;Brodaty, H.;Saigal, N.;Wilson, G. C.;Meiklejohn, J.;Singh, N.;Baune, B. T.;Baker, M.;Foroughi, N.;Wang, Y.;Mavros, Y.;Lampit, A.;Leung, I.;Valenzuela, M. J.",2016,,10.1038/mp.2016.19,0,1007
1007,Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise,"Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.+/-6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.",,"Suo, C.;Singh, M. F.;Gates, N.;Wen, W.;Sachdev, P.;Brodaty, H.;Saigal, N.;Wilson, G. C.;Meiklejohn, J.;Singh, N.;Baune, B. T.;Baker, M.;Foroughi, N.;Wang, Y.;Mavros, Y.;Lampit, A.;Leung, I.;Valenzuela, M. J.",2016,Mar 22,10.1038/mp.2016.19,0,
1008,The burden of white matter hyperintensities is a predictor of progressive mild cognitive impairment in patients with Parkinson's disease,"BACKGROUND AND PURPOSE: To evaluate whether white matter hyperintensities (WMHs) may act as an independent predictor for progression of cognitive status, the authors analyzed the longitudinal effects of WMHs on cognitive dysfunction in non-demented patients with Parkinson's disease (PD). METHODS: A total of 111 patients with PD were enrolled, including subjects with mild cognitive impairment (MCI, n = 65) and cognitively normal subjects (CN, n = 46). These individuals were classified as MCI converters (n = 22) or MCI non-converters (n = 43) and CN converters (n = 18) or CN non-converters (n = 28) based on whether they were subsequently diagnosed with PD dementia or PD-MCI during a minimum 24-month follow-up. The WMH burden and the Cholinergic Pathway Hyperintensities Scale (CHIPS) and their relationships to longitudinal changes in cognitive performance were examined. RESULTS: PD-MCI converters had larger WMH volume (14421.0 vs. 5180.4, P < 0.001) and higher CHIPS score (22.6 vs. 11.2, P = 0.001) compared with PD-MCI non-converters. Logistic regression analysis revealed in patients with PD-MCI that WMH volume (odds ratio 1.616, P = 0.009) and CHIPS score (odds ratio 1.084, P = 0.007) were independently associated with PD dementia conversion. However, WMH volume and CHIPS score did not differ between PD-CN converters and PD-CN non-converters. In patients with PD-MCI, both WMH volume and CHIPS score were closely associated with longitudinal decline in general cognition, semantic fluency and Stroop test scores. CONCLUSIONS: The present study demonstrates that WMH burden is a significant predictor of conversion from PD-MCI to PD dementia and is related to ongoing decline in frontal-lobe-based cognitive performance.","Aged;Aged, 80 and over;Cognition;Disease Progression;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/complications/*pathology;Neuropsychological Tests;Parkinson Disease/complications/*pathology;White Matter/*pathology;Parkinson's disease;dementia converters;white matter hyperintensities","Sunwoo, M. K.;Jeon, S.;Ham, J. H.;Hong, J. Y.;Lee, J. E.;Lee, J. M.;Sohn, Y. H.;Lee, P. H.",2014,Jun,10.1111/ene.12412,0,
1009,Neoplastic angioendotheliosis of the central nervous system,"The patient, a male aged 56, first noticed incomplete urinary retention about 9 months before admission to the hospital. Subsequently he had progressive paresis and hypesthesia of lower extremities. About 7.5 months before admission, he had complete urinary retention, disturbance of all forms of sensation below Th. 6 on the right and Th. 8 on the left. On admission (November 10, 1979), general examination showed no abnormalities. Neurologically, observed were equivocal paresis of the right facial muscle, bilateral hyperactive orbicuralis oris and pharyngeal reflexes, paralysis of lower extremities with diffuse muscular wasting, and severe involvement of all modalities of sensation below the level of Th. 8 on both sides and hyperesthesia in the regions of Th. 6-8 on the right and of L. 2 on the left. After then he showed recurrent aphasia, dysgraphia and dyslexia with sudden onset. These symptoms were improved by steroid therapy, and worsened by decreasing dosage of steroid. Since June 2, 1980, when agraphia and aphasia, without effect of steroid therapy, rapidly occurred, he gradually became drowsy and less responsive. He became completely unresponsive in August and died of bilateral bronchopneumonia on October 6, 1980. On laboratory examination, erythrocyte sedimentation rates, serum urea nitrogens and creatinins were normal throughout the hospitalization. Examinations of CRP showed 1+ to 4+, and CSF proteins were elevated. CT scan in May, 1980, disclosed a large irregular area of lucency in the white matter of the left parietal lobe, and diffuse low density areas in the white matter of the left temporal and bilateral occipital lobes. CT scan in April, 1980, revealed diffuse low density areas in bilateral frontal, occipital, temporal and parietal regions, mainly in the white matter. EEG revealed transient periodic lateralized epileptiform discharges, that is, the periodic sharp waves on the left parietal region. The postmortem examination showed diffuse or scattered numerous necrotic and demyelinating lesions in the spinal cord, and the both cerebral hemispheres in particular bilateral occipital lobes. In these lesions there were extensive proliferations of vessels and demonstrable intravascular proliferations of atypical cell with a large, rounded nuclei and scanty cytoplasm. These findings couldn't be recognized in the other organs including muscles, liver, spleen, bone marrow, lungs, kidneys, heart, adrenals, bladder, pancreas, thyroid gland, prostate, testis and gastrointestinal tract. The proliferation of vessels was dissimilar from increase in number of capillaries after cerebral infarction, because the proliferating vessels were larger than capillaries and were present even in non-necrotic areas. The proliferation of vessels was considered to be an important finding of neoplastic angioendotheliosis as described by Bots (1974) and Strouth et al. (1965).",angioendotheliosis;autopsy;case report;central nervous system;dementia;diagnosis;histology;muscle atrophy;peripheral vascular system;neoplasm,"Sunohara, N.;Mukoyama, M.;Satoyoshi, E.",1982,,,0,
1010,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,,"Brain/*pathology;Cerebral Infarction/*diagnosis/genetics;Dementia, Vascular/*diagnosis/genetics;Female;*Genes, Dominant;Humans;Magnetic Resonance Imaging;Middle Aged;Mutation;Pedigree;Receptors, Notch/*genetics","Sung, P. S.;Pai, M. C.",2008,Dec,,0,
1011,"Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques","Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.",,"Sundman, M. H.;Hall, E. E.;Chen, N. K.",2014,Jan 31,10.4172/2161-0460.1000137,0,
1012,Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): A misdiagnosed disease entity,"Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was originally described in a large Swedish pedigree. Since then, 22 reports describing a total of 13 kindreds and 11 sporadic cases have been published. Inheritance is autosomal dominant, albeit the gene is unknown. Here we report on the clinical findings, genealogical data, brain MRI data, and autopsy/biopsy findings of four probands from three independently ascertained novel families from Norway, Germany and US. We identified a 39-year-old female and her twin sister, a 52-year-old male and a 47-year-old male with progressive neurological illness characterized by personality changes, cognitive decline and motor impairments, such as gait problems, bradykinesia, tremor and rigidity. Brain MRI showed white matter abnormalities with frontal prominence. Brain biopsy/autopsies were consistent with HDLS. HDLS is an under-recognized disease and in reporting these cases, we aim to increase the awareness of the disorder. Due to varied and wide phenotypic presentations, which may imitate several neurodegenerative diseases, HDLS can be difficult to diagnose. Definitive diagnosis can be established only by direct brain tissue examination. Familiarity with the clinical presentation and typical neuroimaging findings may be helpful in narrowing the diagnosis. © 2011 Elsevier B.V. All rights reserved.",beta interferon;methylprednisolone sodium succinate;prednisolone;adult;aggression;Alzheimer disease;apraxia;article;autopsy;biopsy;bradykinesia;CADASIL;cognitive defect;depression;diagnostic error;differential diagnosis;dizziness;drug dose reduction;drug dose titration;dysphagia;dysphasia;dystonia;female;gait disorder;genetic disorder;tonic clonic seizure;hereditary diffuse leukoencephalopathy with axonal spheroid;homonymous hemianopia;human;human tissue;leukoencephalopathy;male;medical record review;memory disorder;multiple sclerosis;mutism;neuroimaging;nuclear magnetic resonance imaging;personality disorder;priority journal;quadriplegia;rigidity;somnolence;spasticity;tremor;white matter,"Sundal, C.;Lash, J.;Aasly, J.;Øygarden, S.;Roeber, S.;Kretzschman, H.;Garbern, J. Y.;Tselis, A.;Rademakers, R.;Dickson, D. W.;Broderick, D.;Wszolek, Z. K.",2012,,,0,
1013,Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis,"Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. Methods: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. Results: One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. Conclusions: Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.",,"Sundal, C.;Baker, M.;Karrenbauer, V.;Gustavsen, M.;Bedri, S.;Glaser, A.;Myhr, K. M.;Haugarvoll, K.;Zetterberg, H.;Harbo, H.;Kockum, I.;Hillert, J.;Wszolek, Z.;Rademakers, R.;Andersen, O.",2015,1,,0,
1014,"Abnormal functional connectivity in patients with vascular cognitive impairment, no dementia: a resting-state functional magnetic resonance imaging study","The functional connectivity (FC) method was used to investigate the changes in the resting state of patients with vascular cognitive impairment, no dementia (VCIND). Resting-state functional magnetic resonance images (fMRIs) were acquired from 16 patients with subcortical ischemic vascular disease (SIVD) who fulfilled the criteria for VCIND, as well as 18 age- and sex-matched subjects with SIVD with no cognitive impairment (control group). Posterior cingulate cortex connectivity was gathered by investigating synchronic low-frequency fMRI signal fluctuations with a temporal correlation method. Compared with the control group, the patients showed FC decrease in the left middle temporal gyrus, the left anterior cingulate/left middle frontal gyrus, the right caudate, the right middle frontal gyrus, and the left medial frontal gyrus/paracentral lobule. There were also some regions that showed increased connectivity. These regions included the right inferior temporal gyrus, the left middle temporal gyrus, the left precentral gyrus, and the left superior parietal lobule. Our findings revealed the change in resting-state patterns of neuronal activity in patients with VCIND. This change may be caused by subcortical white matter lesions that destroyed direct and indirect fiber tract connectivity across the cerebral white matter and influenced the cortical FC and hypoperfusion resulted from small vascular disease. The results of the increased connectivity may be evoked by the compensatory recruitment and plasticity mechanism. Our findings suggest that the simplicity and noninvasiveness of this method makes it a potential tool to help thoroughly understand the pathogenesis of VCIND.","Aged;Brain/pathology;Brain Ischemia/pathology/psychology;Cerebral Cortex/pathology;Cerebrovascular Disorders/complications/ pathology/psychology;Cognition Disorders/etiology/ pathology/psychology;Data Interpretation, Statistical;Female;Humans;Image Processing, Computer-Assisted;Ischemic Attack, Transient/pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Net/pathology;Neural Pathways/ pathology;Neuropsychological Tests;Oxygen/blood;Stroke/pathology/psychology","Sun, Y. W.;Qin, L. D.;Zhou, Y.;Xu, Q.;Qian, L. J.;Tao, J.;Xu, J. R.",2011,Oct 1,10.1016/j.bbr.2011.05.006,0,
1015,Relationship between the data from MR-diffusion tensor imaging and the clinical cognitive evaluation in Alzheimer's disease,"OBJECTIVE: To determine the relationship between the extent of the damage and clinical data in Alzheimer's disease (AD). METHODS: Twenty-two patients with AD and twenty-two controls received MR-diffusion tensor scanning. The fractional anisotropy (FA) values of white matter in AD patients were measured respectively in parietal lobe and the genu of corpus callosum. Independent-samples t-test for non-paired data was used to test differences between AD and controls for FA values. Correlation analysis was applied to reveal the correlations between FA values in each region and the MMSE, FOM, RVR, BD and DS scores. RESULTS: Positive correlations were found between FA values in left parietal lobe and FOM/DS, and between FA values in genu of corpus callosum and MMSE scores. CONCLUSIONS: In AD, the MR-DTI can reflect the relationship between the degree of white matter abnormalities and the cognitive impairment.",Aged;Alzheimer Disease/ diagnosis/pathology/psychology;Anisotropy;Cerebral Cortex/ pathology;Cognition;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Wechsler Scales,"Sun, Y.;Du, X. K.;Zhang, Z. X.;Chen, X.",2004,Apr,,0,
1016,Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study,"Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO2. A correlation between the decrease in rCMRO2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information.","Adult;Brain/ metabolism/pathology/radionuclide imaging;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Multiple Sclerosis/ metabolism/pathology/radionuclide imaging;Time Factors;Tomography, Emission-Computed","Sun, X.;Tanaka, M.;Kondo, S.;Okamoto, K.;Hirai, S.",1998,Apr,,0,
1017,Early frontal structural and functional changes in mild white matter lesions relevant to cognitive decline,"White matter lesions (WMLs) are of considerable research interest because of their high prevalence and serious consequences, such as stroke and dementia. Most existing studies of WMLs have focused on severe WMLs, but mild WMLs, which are clinically and fundamentally significant, have been largely neglected. The present study is a comprehensive investigation on the injury pattern and on the anatomical, functional, and cognitive changes related to mild WMLs. These results may provide better understanding mild WMLs. Fifty-one human subjects with mild WMLs and 49 control participants completed serial neuropsychological tests and underwent a 3-T magnetic resonance imaging (MRI) scan that included diffusion tensor imaging, a resting-state functional MRI, and a structural MRI. We found declines in cognitive functions such as global function, executive function, and episodic memory in mild WMLs subjects. The white matter injuries in the mild WMLs subjects were mainly in the fibers that projected to frontal areas, while gray matter structures were relatively intact. The overall resting state function of the frontal area was significantly increased. The integrity of the neural fibers in the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus was significantly correlated with the cognitive scores in executive function and episodic memory in both the control and the mild WMLs group. These findings demonstrate that mild WMLs subjects exhibit abnormalities in both white matter structure and functional intrinsic brain activity and that such changes are related to several types of cognitive dysfunction.","Aged;Aged, 80 and over;Brain Mapping;Cognition Disorders/ etiology;Corpus Callosum/ pathology;Diffusion Tensor Imaging;Female;Frontal Lobe/blood supply/ pathology;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/ complications/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Oxygen/blood;Pyramidal Tracts/blood supply/pathology;Statistics as Topic","Sun, X.;Liang, Y.;Wang, J.;Chen, K.;Chen, Y.;Zhou, X.;Jia, J.;Zhang, Z.",2014,,10.3233/jad-131709,0,
1018,The relationship between plasma amyloid-beta peptides and the medial temporal lobe in the homebound elderly,"BACKGROUND: The ratio of high amyloid-beta peptide40 (Abeta40) and low Abeta42 in plasma predicts the risk of Alzheimer's disease (AD) and is associated with episodic recall in depression. We thus examined the relationship between plasma Abeta levels and brain volumes. METHODS: Homebound elders (N = 352) who had undergone brain MRI were used. Plasma Abeta1-40 and Abeta1-42 were measured by ELISA. Volumes of medial temporal regions, including the amygdala and hippocampus, were manually measured. RESULTS: Amygdala volume was associated with log(10) of plasma Abeta1-42 (beta = +0.19, SE = 0.07, p = 0.005) after adjusting for AD, infarcts, white matter hyperintensities and demographics. In the absence of dementia, decreasing quartiles of plasma Abeta1-42 (Mean + SD ml: Q4 = 4.1 +/- 0.8; Q3 = 3.9 +/- 0.7; Q2 = 3.6 +/- 0.8 and Q1 = 3.7 +/- 0.8, p = 0.01) and increasing quartiles of plasma Abeta1-40/1-42 ratio were associated with smaller amygdala volume. Those depressed subjects with a high plasma Abeta1-40/1-42 ratio had smaller amygdala (Mean + SD ml: 3.3 +/- 0.8 vs. 3.6 +/- 0.8, p = 0.04) and total brain volume (Mean + SD liter: 0.95 +/- 0.07 vs. 1.04 +/- 0.12, p = 0.005), and had a higher rate of MCI (67 vs. 36%, p = 0.02) than those with a low plasma Abeta1-40/1-42 ratio. CONCLUSIONS: The combination of low plasma Abeta1-42 concentration and atrophy of the medial temporal lobe structures, which regulates mood and cognition, may represent a biomarker for a prodromal stage of AD.","Aged;Aged, 80 and over;Amygdala/*pathology;Amyloid beta-Peptides/*blood;Analysis of Variance;Cognition Disorders/blood/pathology;Dementia/blood/diagnosis;Depression/blood/pathology;Enzyme-Linked Immunosorbent Assay;Female;Hippocampus/*pathology;Homebound Persons/*psychology;Humans;Magnetic Resonance Imaging;Male;Mental Disorders/*blood/*pathology;Psychiatric Status Rating Scales","Sun, X.;Bhadelia, R.;Liebson, E.;Bergethon, P.;Folstein, M.;Zhu, J. J.;Mwamburi, D. M.;Patz, S.;Qiu, W. Q.",2011,Jun,10.1002/gps.2568,0,
1019,Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging,"Using magnetic resonance diffusion tensor imaging (DTI), the present study investigates changes in both gray and white matter in the APPsw transgenic mouse (Tg2576), a model of beta-amyloid plaque deposition associated with Alzheimer's disease (AD). DTI analyses were performed in cross-sectional groups of transgene-positive and -negative mice at 8, 12, 16, and 18 months of age to assess the magnitude of water diffusion in gray matter (i.e., Tr(D)) and changes in diffusion in white matter that may be indicative of axonal degeneration (i.e., reduced water diffusion parallel to axonal tracts, lambda(||)) and myelin degradation (i.e., increased water diffusion perpendicular to axonal tracts, lambda(perpendicular)). No appreciable changes in gray or white matter were observed between the APPsw and the age-matched control mice at 8 months of age. Reduced Tr(D) and lambda(||) were observed in gray and white matter, respectively, for the APPsw mice at ages greater than 8 months, which coincides with the time period when appreciable amyloid plaque accumulation was confirmed by ex vivo histopathological studies. The decreases in lambda(||) suggest the presence of axonal injury in multiple white matter tracts of APPsw mice. Unlike lambda(||), lambda(perpendicular) was unaltered between control and APPsw mice in most white matter tracts. However, in the corpus collosum (CC), lambda(perpendicular) increased at 16 and 18 months of age, suggesting the possibility of myelin damage in the CC at these later ages. This work demonstrates the potential for DTI as a noninvasive modality to detect evolving pathology associated with changes in tissue water diffusion properties in brain tissues.","Aging/genetics/ metabolism/pathology;Alzheimer Disease/genetics/ metabolism;Amyloidosis/genetics/ metabolism/pathology;Animals;Brain/ metabolism/pathology;Brain Injuries/genetics/ metabolism/pathology;Diffusion Magnetic Resonance Imaging/methods;Disease Models, Animal;Female;Male;Mice;Mice, Transgenic","Sun, S. W.;Song, S. K.;Harms, M. P.;Lin, S. J.;Holtzman, D. M.;Merchant, K. M.;Kotyk, J. J.",2005,Jan,10.1016/j.expneurol.2004.09.006,0,
1020,In vivo diffusion tensor imaging of amyloid-beta-induced white matter damage in mice,"BACKGROUND: Diffusion tensor imaging (DTI) suggests the presence of white matter abnormality at the prodromal stage in human Alzheimer's disease (AD). OBJECTIVE: To use a mouse model of AD to determine whether the white matter abnormality detected by in vivo DTI is associated with functional deficits and axon damage. METHODS: Amyloid-beta1-42 (Abeta1-42) was injected into the left lateral ventricle in mice. Two months after the injection, in vivo DTI and visual evoked potential (VEP) recordings were performed, followed by immunohistochemistry of phosphorylated neurofilament and myelin basic protein. RESULTS: DTI of Abeta1-42-treated mice showed a significant increase of radial diffusivity in white matter including the optic nerves and tracts. The abnormality was associated with decreased amplitude and increased latency of VEP. Immunohistochemistry confirmed a significant loss of axons and myelin integrity. CONCLUSION: White matter damage induced by Abeta1-42 in mice can be detected non-invasively by DTI.","Amyloid beta-Peptides/ toxicity;Animals;Body Weight/drug effects;Diffusion Magnetic Resonance Imaging/ methods;Disease Models, Animal;Evoked Potentials, Visual/drug effects;Female;Functional Laterality;Leukoencephalopathies/ chemically induced/ diagnosis/physiopathology;Male;Mice;Mice, Inbred C57BL;Myelin Basic Protein/metabolism;Neurofilament Proteins/metabolism;Optic Nerve/pathology;Peptide Fragments/ toxicity","Sun, S. W.;Liang, H. F.;Mei, J.;Xu, D.;Shi, W. X.",2014,,10.3233/jad-130236,0,
1021,"Lipid and hyperglycemia factors in first-ever penetrating artery infarction, a comparison between different subtypes","Background: The pathogenesis and progression of branch atheromatous disease (BAD), which differs from lipohyalinotic degeneration (LD), remains controversial. Few studies have investigated the lipid indices and glycometabolism status factors for BAD in first-ever penetrating artery infarction (PAI). Methods: We retrospectively examined acute stroke patients with PAI admitted within 3 days after stroke. All patients underwent diffusion weight magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) and/or computed tomography angiography (CTA). Progression was defined as an increase by 2 point or higher in the National Institutes of Health Stroke Scale score. The characteristics, clinical data were statistically analyzed. Results: BAD and LD were diagnosed in 142 (57%) and 107 (43%) patients, respectively. Patients with BAD had higher low-density lipoprotein cholesterol (LDL-C) compared with those with LD (p =.013). Elevated LDL-C was related to early neurological deterioration in patients with BAD (p =.045). The percentage of lenticulostriate arterial (LSA) infarction was greater than that of the pontine penetrating arterial (PPA) infarction in acute PAI (75.1% vs. 24.9%; p <.001). PPA infarction was more prevalent in the BAD group compared with the LD group (34.5% vs. 12.1%, p <.001). The PPA infarction had older age at onset and higher HbA1c concentrations than those with the LSA infarction (p =.014, p =.036 respectively) in the BAD and LD patients, respectively. Conclusion: LDL-C may be associated with both the pathogenesis and progression of intracranial BAD. The LSA infarction was the most frequently subtypes in PAI. Age at onset and HbA1c seem to be closely associated with the PPA infarction of first-ever PAI.",apolipoprotein A1;apolipoprotein B;hemoglobin A1c;high density lipoprotein cholesterol;lipid;low density lipoprotein cholesterol;triacylglycerol;adult;article;cerebral artery disease;comparative study;computed tomographic angiography;diffusion weighted imaging;disease association;female;human;hyperglycemia;magnetic resonance angiography;major clinical study;male;mental deterioration;middle aged;National Institutes of Health Stroke Scale;onset age;priority journal;retrospective study,"Sun, S.;Wang, Y.;Wang, Y.;Men, X.;Bao, J.;Hu, X.;Lu, Z.",2017,,10.1002/brb3.694,0,
1022,Clinical and MRI manifestation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Objective: To investigate the relationship between the clinical manifestations and MRI changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Four patients from the same generation in a family underwent the routine MRI and MRA. Three cases (the proband and 2 sisters) were comfirmed by the Notch3 genetic testing and skin biopsy, other one (the brother) was diagnosed as cerebral autosomal dominant arteriopathy by MRI and clinical examination. The brain lesion signal characteristic, distribution area, distribution regularity, brain atrophy and the related clinical manifestations were all analysed. Results: In the proband, skin biopsy revealed granular osmiophilic materials on the surface of vascular smooth muscle cells of subcutaneous arterioles, gene testing detected Notch3 gene mutation, and clinical presentations indicated progressive memory deterioration associated with hemiparesis. There were 5 affected family members (onset at 43-48 years old) mainly with dementia and hemiparesis in 2 consequential generations. MRI showed multiple small focal cerebral infarcts, extensive white matter hypointensity at deep part of the brain and O'Sullivan sign. Approximately symmetric and extensive foci were found at the white matter of bilateral subcortex of frontal and parietal lobe and beside the lateral cerebral ventricle. Encephalatrophy, subcortical cerebral lacunar infarct, ""^"" shape sign, various old basal ganglion and brain stem lacunar infarcts, black holes sign and pepperpot sign were also seen. Mini-Mental State Examination (MMSE) scores were 21 in the proband, 23 in the elder sister, 22 in the younger sister and 29 in the brother. Coulthard scores were 32 in the proband, 29 in the elder sister, 25 in the younger sister and 27 in the brother. Conclusion: Coulthard score indicates that CADASIL patients with dementia may have more extensive MRI changes, but Coulthard score can not correctly reflect the clinical manifestations in the early stage of the disease.",Notch3 receptor;adult;arteriole;article;basal ganglion;brain atrophy;brain cortex;brain disease;brain infarction;brain region;brain stem infarction;CADASIL;case report;cell surface;clinical examination;controlled study;dementia;family;female;frontal lobe;gene mutation;genetic analysis;hemiparesis;human;lateral brain ventricle;male;memory disorder;Mini Mental State Examination;nuclear magnetic resonance imaging;onset age;parietal lobe;scoring system;skin biopsy;vascular smooth muscle;white matter,"Sun, B. L.;Diao, Y. S.;Zhang, J. P.;Zhou, X. Y.;Yuan, Y.",2007,,,0,
1023,Cognitive impairment in relapsing-remitting multiple sclerosis can be predicted by imaging performed several years earlier,"Cognitive deficits in multiple sclerosis (MS) are common and correlate with contemporary MRI brain abnormalities, particularly atrophy, but the ability of imaging early in the disease to predict later cognitive impairment remains to be determined. Thirty relapsing-remitting MS patients recruited within three years of the onset of the disease, and in whom MRI had been performed at baseline and a year later, were assessed neuropsychologically five years later. Imaging parameters accounting for significant variance in cognitive performance were identified using multiple regressions, once confounding variables were controlled. Patients performed significantly worse than expected on tests of attention/speed of information processing and half of them had experienced some decline in IQ in relation to premorbid estimates. The rate of global brain atrophy in the first year of the study accounted for significant variance in the overall cognitive performance, and in memory and attention/speed of information processing. Poor performance on attention tests was associated with high T1-weighted lesion volume and reduced magnetization transfer ratio (MTR) in normal-appearing white matter (NAWM). These results suggest that neuroaxonal loss was identified early in the disease, and its rate of progression, predicted cognitive impairment later in the disease. Neuroaxonal loss is likely to affect commissural and association fibres that subserve the cognitive processes impaired in MS. © 2008 SAGE Publications Los Angeles, London, New Delhi and Singapore.",,"Summers, M. M.;Fisniku, L. K.;Anderson, V. M.;Miller, D. H.;Cipolotti, L.;Ron, M. A.",2008,March,,0,
1024,Intravascular lymphoma masquerading as multiembolic stroke developing after coronary artery by-pass surgery,"Background: Intravascular lymphoma (IVL) is a very rare non-Hodgkin type lymphoproliferative disorder characterized by neoplastic growth of lymphoid cells within the lumen of capillaries, small veins, and arterioles. The neoplastic cells cannot reach the parenchyma because of the loss of adhesion molecules during malignant transformation. Multifocal vascular occlusions caused by proliferation of malignant lymphocytes in the lumen result in diffuse thrombosis and tissue infarction. The clinical symptoms of the disease are dependent on the specific organ involvement which most often includes the central nervous system and skin. Neurologic presentation includes focal sensory or motor deficits, altered sensorium, rapidly progressive dementia, seizures, ataxia, and vertigo. Case Report: We report a patient with IVL whose symptoms developed on the second postoperative day of coronary artery-bypass surgery imitating a multiembolic stroke. Magnetic resonance imaging showed widespread ischemic subcortical lesions. The patient's clinical status worsened irrespective of supportive medical treatment. The diagnosis was established by autopsy. Conclusion: IVL may mimic ischemic stroke. IVL is not often diagnosed before death because of the intravascular growth pattern of the tumor cells and a fulminant clinical course. IVL may be considered in the differential diagnosis of ischemic stroke patients with progressive worsening despite medical management. Copyright © 2009 by Lippincott Williams & Wilkins.",,"Sumer, M.;Ozon, A. O.;Bakar, B.;Cila, A.;Ruacan, S.",2009,March,,0,
1025,Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings,"OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. RESULTS: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia.","Adolescent;Adult;Cerebral Cortex/ metabolism/pathology/radionuclide imaging;Cognition;Dementia, Vascular/diagnosis/ metabolism/psychology;Frontal Lobe/metabolism/pathology/radionuclide imaging;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Tomography, Emission-Computed","Sultzer, D. L.;Mahler, M. E.;Cummings, J. L.;Van Gorp, W. G.;Hinkin, C. H.;Brown, C.",1995,Aug,,0,
1026,Diffusion tensor imaging in normal aging and neuropsychiatric disorders,"The application of diffusion imaging to the quantitative study of the effects of normal aging and neuropsychiatric diseases on brain tissue microstructure has witnessed its greatest development just over the last few years. Measures derived from diffusion imaging have already been shown to have great utility in identifying age- and disease-related degradation of regional microstructure, particularly of white matter. Investigations comparing diagnoses hold promise for contribution to differential diagnosis. Correlations with cognitive and motor performance provide evidence for functional ramifications of these diffusion measures. © 2002 Elsevier Science Ireland Ltd. All rights reserved.",,"Sullivan, E. V.;Pfefferbaum, A.",2003,1,,0,
1027,Magnetic resonance relaxometry reveals central pontine abnormalities in clinically asymptomatic alcoholic men,"BACKGROUND: Central pontine myelinolysis (CPM) is a rare, debilitating, life-threatening condition, associated with chronic alcoholism, rapid correction of hyponatremia, and advanced age. It is unknown, however, whether older alcoholic patients who by age and diagnosis are at risk for CPM have objectively determined neuroimaging evidence of preclinical CPM that could be valuable in understanding its development and in initiating appropriate treatment. Accordingly, we examined central pontine magnetic resonance (MR) transverse relaxation time (T2), which reflects myelin and axonal integrity when measured in white matter and is prolonged with pathology that causes increased free water content in tissue. METHODS: The subjects were 46 alcoholic men who were abstinent from alcohol for about 1 month and were asymptomatic for CPM, 9 men and 1 woman with alcoholic Korsakoff's syndrome (KS), and 74 healthy control men. All subjects received coronally acquired dual-echo MR imaging (MRI), from which T2 times were calculated in central pons. MRI films were read clinically and independently of relaxometry results. Hematological and neuropsychological data were also available for many subjects. RESULTS: Only the KS group showed prolonged T2 times; however, pontine T2 prolongation increased significantly with older age in the asymptomatic alcoholics but not controls. Clinical radiological readings detected pontine signal hyperintensity in five KS subjects (two without dementia and three with dementia), one control, and no alcoholic patient. Hematologic indexes of macrocytic anemia and nutritional deficiency and neuropsychological measures of verbal and nonverbal fluency correlated with prolonged T2 times in alcoholic men. CONCLUSIONS: This CPM-like condition, manifest as prolonged T2, may occur with higher incidence than previously thought in clinically asymptomatic alcoholism and may contribute to neuropsychological compromise of initiation and production. Preclinical detection of abnormal pontine signal properties with MR relaxometry may identify patients at high risk for developing CPM.",Adult;Aged;Alcoholism/complications/ physiopathology;Dementia/etiology/physiopathology;Erythrocyte Count;Erythrocyte Indices;Female;Humans;Korsakoff Syndrome/physiopathology;Magnetic Resonance Imaging;Male;Middle Aged;Pons/ physiopathology;Serum Albumin/analysis,"Sullivan, E. V.;Pfefferbaum, A.",2001,Aug,,0,
1028,Primary central nervous system anaplastic large-cell lymphoma mimicking lymphomatosis cerebri,"Primary central nervous system lymphoma (PCNSL) is usually diffuse large B-cell lymphoma. Anaplastic large-cell lymphoma (ALCL) rarely occurs in the central nervous system. PCNSL always presents as single or multiple nodular contrast-enhancing mass lesions within T2-hyperintense areas on magnetic resonance imaging (MRI). Infrequently, diffuse infiltrating change with little contrast enhancement called lymphomatosis cerebri can be seen in PCNSL. In this report, we describe a 75-year-old immunocompetent man who had progressive dementia. On MRI, diffuse white matter lesions with little contrast enhancement were observed to gradually progress, which was clinically consistent with his worsening condition. A biopsy specimen revealed non-destructive, diffusely infiltrating, anaplastic large CD30-positive lymphoma, indicating a diagnosis of ALCL. After the biopsy, he was treated by whole brain irradiation (total 46 Gy) and focal boost irradiation (total 14 Gy). However, his performance status worsened and there was no symptom improvement. The patient died 8 months after symptom onset. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described herein. © 2012 The Japan Society of Brain Tumor Pathology.",,"Sugino, T.;Mikami, T.;Akiyama, Y.;Wanibuchi, M.;Hasegawa, T.;Mikuni, N.",2013,January,,0,
1029,Evaluation of the anisotropy in the patients with Alzheimer's disease,"Diffusion-weighted MR imaging was performed in 5 control subjects and 8 patients with Alzheimer's disease(AD). The mean values of fractional anisotropy(FA) were calculated in the genu and splenium of the corpus callosum, and anterior and posterior cerebral white matter. The FA value of the posterior white matter in patients with AD was significantly lower than that of controls. Fractional anisotropy may be useful in the diagnosis of AD.",Aged;Alzheimer Disease/ diagnosis;Anisotropy;Female;Humans;Magnetic Resonance Imaging;Male,"Sugihara, S.;Matsusue, E.;Kinoshita, T.;Ogawa, T.",2003,Jan,,0,
1030,Usefulness of diffusion tensor imaging of white matter in Alzheimer disease and vascular dementia,"PURPOSE: To evaluate the usefulness of diffusion tensor imaging in detecting the water diffusivity caused by neuropathological change in Alzheimer disease and vascular dementia. MATERIAL AND METHODS: Twenty patients with Alzheimer disease, 20 with vascular dementia, and 10 control subjects were examined. Diffusion tensor imaging applied diffusion gradient encoding in six non-collinear directions. Fractional anisotropy values were compared in the genu and splenium of the corpus callosum, and anterior and posterior white matter among the three groups. RESULTS: In the patients with Alzheimer disease, fractional anisotropy values of the posterior white matter were significantly lower than those of controls. In patients with vascular dementia, fractional anisotropy values of the anterior white matter tended to be lower than those of the posterior white matter (P=0.07). CONCLUSION: Diffusion tensor imaging reflects the neuropathological changes in the white matter, and may be useful in the diagnosis of Alzheimer disease and vascular dementia.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Case-Control Studies;Corpus Callosum/pathology;Dementia, Vascular/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male","Sugihara, S.;Kinoshita, T.;Matsusue, E.;Fujii, S.;Ogawa, T.",2004,Oct,,0,1031
1031,Usefulness of diffusion tensor imaging of white matter in Alzheimer disease and vascular dementia,"PURPOSE: To evaluate the usefulness of diffusion tensor imaging in detecting the water diffusivity caused by neuropathological change in Alzheimer disease and vascular dementia. MATERIAL AND METHODS: Twenty patients with Alzheimer disease, 20 with vascular dementia, and 10 control subjects were examined. Diffusion tensor imaging applied diffusion gradient encoding in six non-collinear directions. Fractional anisotropy values were compared in the genu and splenium of the corpus callosum, and anterior and posterior white matter among the three groups. RESULTS: In the patients with Alzheimer disease, fractional anisotropy values of the posterior white matter were significantly lower than those of controls. In patients with vascular dementia, fractional anisotropy values of the anterior white matter tended to be lower than those of the posterior white matter (P=0.07). CONCLUSION: Diffusion tensor imaging reflects the neuropathological changes in the white matter, and may be useful in the diagnosis of Alzheimer disease and vascular dementia.",,"Sugihara, S.;Kinoshita, T.;Matsusue, E.;Fujii, S.;Ogawa, T.",1987,Oct,,0,
1032,Primary central nervous system lymphoma initially mimicking lymphomatosis cerebri: An autopsy case report,"A 59-year-old immunocompetent man was admitted to our hospital because of progressive dementia with concomitant bilateral uveitis. The first brain MRI revealed diffuse hyperintense lesions in the cerebral white matter of both hemispheres on a T2-weighted image and fluid-attenuated inversion recovery image. However, another MRI taken more than 1 month later revealed enhanced cohesive mass lesions in the bilateral thalami, in addition to the white matter lesions. The white matter lesions were slightly hyperintense on a diffusion-weighted image and apparent diffusion coefficient map image, suggesting vasogenic edema. One year after the onset of uveitis, he died of respiratory failure. Pathological diagnosis was diffuse large B-cell lymphoma with perivascular proliferation and diffuse scattered infiltration in the cerebrum and brainstem. Microscopically, cohesive mass lesions in the bilateral thalami were a massive cluster of lymphoma cells. This is a case of primary CNS lymphoma (PCNSL) mimicking 'lymphomatosis cerebri (LC)' at first but later exhibiting typical mass lesions, giving rise to the possibility that cases of LC might unmask features of regular lymphomas in their later course more often than believed thus far. © 2009 Japanese Society of Neuropathology.",,"Sugie, M.;Ishihara, K.;Kato, H.;Nakano, I.;Kawamura, M.",2009,December,,0,
1033,Longitudinal segmentation of age-related white matter hyperintensities,"Although white matter hyperintensities evolve in the course of ageing, few solutions exist to consider the lesion segmentation problem longitudinally. Based on an existing automatic lesion segmentation algorithm, a longitudinal extension is proposed. For evaluation purposes, a longitudinal lesion simulator is created allowing for the comparison between the longitudinal and the cross-sectional version in various situations of lesion load progression. Finally, applied to clinical data, the proposed framework demonstrates an increased robustness compared to available cross-sectional methods and findings are aligned with previously reported clinical patterns.",apolipoprotein E4;age;aged;aging;algorithm;allele;Alzheimer disease;article;brain atrophy;brain size;conceptual framework;controlled study;cross-sectional study;female;human;image segmentation;longitudinal study;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;priority journal;quantitative analysis;risk factor;signal noise ratio;white matter;white matter hyperintensity volume;white matter lesion,"Sudre, C. H.;Cardoso, M. J.;Ourselin, S.",2017,,10.1016/j.media.2017.02.007,0,
1034,APOE ε4 status is associated with white matter hyperintensities volume accumulation rate independent of AD diagnosis,"To assess the relationship between carriage of APOE ε4 allele and evolution of white matter hyperintensities (WMHs) volume, we longitudinally studied 339 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort with diagnoses ranging from normal controls to probable Alzheimer's disease (AD). A purpose-built longitudinal automatic method was used to segment WMH using constraints derived from an atlas-based model selection applied to a time-averaged image. Linear mixed models were used to evaluate the differences in rate of change across diagnosis and genetic groups. After adjustment for covariates (age, sex, and total intracranial volume), homozygous APOE ε4ε4 subjects had a significantly higher rate of WMH accumulation (22.5% per year 95% CI [14.4, 31.2] for a standardized population having typical values of covariates) compared with the heterozygous (ε4ε3) subjects (10.0% per year [6.7, 13.4]) and homozygous ε3ε3 (6.6% per year [4.1, 9.3]) subjects. Rates of accumulation increased with diagnostic severity; controls accumulated 5.8% per year 95% CI: [2.2, 9.6] for the standardized population, early mild cognitive impairment 6.6% per year [3.9, 9.4], late mild cognitive impairment 12.5% per year [8.2, 17.0] and AD subjects 14.7% per year [6.0, 24.0]. Following adjustment for APOE status, these differences became nonstatistically significant suggesting that APOE ε4 genotype is the major driver of accumulation of WMH volume rather than diagnosis of AD.",amyloid beta protein[1-42];apolipoprotein E4;age;aged;allele;Alzheimer disease;APOE epsilon4 gene;article;brain size;cohort analysis;controlled study;correlational study;disease severity;female;follow up;genetic association;genotype;heterozygosity;homozygosity;human;longitudinal study;major clinical study;male;mild cognitive impairment;neuroimaging;protein cerebrospinal fluid level;sex difference;white matter lesion,"Sudre, C. H.;Cardoso, M. J.;Frost, C.;Barnes, J.;Barkhof, F.;Fox, N.;Ourselin, S.",2017,,10.1016/j.neurobiolaging.2017.01.014,0,
1035,Bayesian Model Selection for Pathological Neuroimaging Data Applied to White Matter Lesion Segmentation,"In neuroimaging studies, pathologies can present themselves as abnormal intensity patterns. Thus, solutions for detecting abnormal intensities are currently under investigation. As each patient is unique, an unbiased and biologically plausible model of pathological data would have to be able to adapt to the subject's individual presentation. Such a model would provide the means for a better understanding of the underlying biological processes and improve one's ability to define pathologically meaningful imaging biomarkers. With this aim in mind, this work proposes a hierarchical fully unsupervised model selection framework for neuroimaging data which enables the distinction between different types of abnormal image patterns without pathological a priori knowledge. Its application on simulated and clinical data demonstrated the ability to detect abnormal intensity clusters, resulting in a competitive to improved behavior in white matter lesion segmentation when compared to three other freely-available automated methods.",,"Sudre, C. H.;Cardoso, M. J.;Bouvy, W. H.;Biessels, G. J.;Barnes, J.;Ourselin, S.",2015,,,0,
1036,White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort,"Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.","CI, Confidence interval;FTD, Frontotemporal dementia;IQR, Inter Quartile Range;PS, Presymptomatic;S, Symptomatic;TIV, Total Intracranial volume;WMH, White matter hyperintensity","Sudre, C. H.;Bocchetta, M.;Cash, D.;Thomas, D. L.;Woollacott, I.;Dick, K. M.;van Swieten, J.;Borroni, B.;Galimberti, D.;Masellis, M.;Tartaglia, M. C.;Rowe, J. B.;Graff, C.;Tagliavini, F.;Frisoni, G.;Laforce, R., Jr.;Finger, E.;de Mendonca, A.;Sorbi, S.;Ourselin, S.;Cardoso, M. J.;Rohrer, J. D.;Genetic Ftd Initiative, Genfi",2017,,,0,
1037,Executive testing predicts functional loss in subjects with white matter lesions,"In order to assess ecological validity of executive function (EF) tests and the impact of EF dysfunction on functional status in elderly subjects with moderate and severe subcortical white matter hyperintensities (WMHs), we made a correlation analysis between EF scores and two measures of Instrumental Activities of Daily Living (IADL). Trail-making test and CLOX correlated with the ability to perform IADL in subjects with severe WMH. EF tests might present low ecological validity for those with WMH below severe stage.",aged;article;assessment of humans;Cambridge Cognitive Examination;clinical article;Clinical Dementia Rating;controlled study;correlation analysis;cross-sectional study;executive function test;female;Functional Activities Questionnaire;functional assessment;functional disease;functional status;human;Instrumental Activities of Daily Living;male;Mini Mental State Examination;multiinfarct dementia;neuroimaging;neuropsychological test;neuropsychology;nuclear magnetic resonance imaging;psychologic test;task performance;white matter hyperintensity;white matter lesion;working memory,"Sudo, F. K.;Alves, G. S.;Ericeira-Valente, L.;Alves, C. E. O.;Tiel, C.;Moreira, D. M.;Laks, J.;Engelhardt, E.",2015,,,0,
1038,"White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment","Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods: Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years) were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15) were compared to normal controls (NC, n=11) and correlated with Fazekas scale. Results: VaMCI performed significantly worse than NC in Trail-Making Test (TMT) B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG) final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors), difference TMT B-A and CAMCOG total score. Conclusion: Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.",aged;article;behavior;clinical article;cognition;controlled study;executive function;Fazekas scale;female;Hachinski Ischemic Score;human;male;mild cognitive impairment;Mini Mental State Examination;assessment of humans;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;white matter,"Sudo, F. K.;Alves, C. E. O.;Alves, G. S.;Ericeira-Valente, L.;Tiel, C.;Moreira, D. M.;Laks, J.;Engelhardt, E.",2013,,,0,
1039,Dysexecutive syndrome and cerebrovascular disease in non-amnestic mild cognitive impairment: A systematic review of the literature,"Objective: Non-amnestic dysexecutive Vascular Mild Cognitive Impairment (VaMCI) may represent preclinical Vascular Dementia (VaD). The aim of this study was to summarize the clinical, neuropsychological and neuroimaging aspects of VaMCI; and to assess its patterns of progression to dementia. Methods: Searches were made in the ISI Web of Knowledge, PubMed and Lilacs databases, using the terms ""mild cognitive impairment"" and ""executive function"". Altogether, 944 articles were retrieved. Results: VaMCI cases had poorer performances on fronto-executive tasks, a higher prevalence of stroke, presence of periventricular and profound white matter hyperintensities on MRI images, as well as more extrapyramidal signs and behavioral symptoms. Executive dysfunction might be associated with disconnection of fronto-parietal-subcortical circuits. Progression to dementia was associated with baseline deficits in executive function, in simple sustained attention and language, and large periventricular WMH. Discussion: VaMCI develops with impairment in non-memory domains and subcortical white matter changes on MRI images, which are consistent with clinical and neuroimaging findings in VaD.",cerebrovascular disease;executive function;mild cognitive impairment;neuroimaging;neuropsychology;vascular dementia,"Sudo, F. K.;Alves, C. E. O.;Alves, G. S.;Ericeira-Valente, L.;Tiel, C.;Moreira, D. M.;Laks, J.;Engelhardt, E.",2012,Jul-Sep,,0,
1040,Low serum n-3 polyunsaturated fatty acid/n-6 polyunsaturated fatty acid ratio predicts neurological deterioration in Japanese patients with acute ischemic stroke,"Background: Epidemiological and clinical trials have shown that n-3 polyunsaturated fatty acids (PUFAs) reduce the incidence of coronary heart disease or stroke. However, the association between PUFAs and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of serum PUFAs on early neurological deterioration (END) in patients with acute ischemic stroke. Methods: In this retrospective study, we enrolled 281 Japanese patients (mean age: 75 ± 13 years; 165 males) with acute ischemic stroke diagnosed within 24 h of onset. General blood examinations, including PUFAs (n-3 PUFAs: eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, and n-6 PUFAs: arachidonic acid, AA), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within a 72-hour period. Statistical significance between the END and non-END group was assessed using Wilcoxon rank sum tests or Student's t tests for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. Results: END was observed in 75 patients (26.7%). Diabetes mellitus (p = 0.003), high-sensitivity C-reactive protein (hs-CRP) level (p < 0.001), prior stroke (p = 0.035), ischemic heart disease (p = 0.029), EPA/AA ratio (p = 0.003), DHA/AA ratio (p = 0.002), EPA+DHA/AA ratio (p = 0.002), diagnosis of small vessel disease (p = 0.004) and admission NIHSS score (p < 0.001) were significantly associated with END. We used separate multiple logistic regression analyses for the EPA/AA, DHA/AA and EPA+DHA/AA ratios, because EPA and DHA are considered covariant factors (r = 0.544; p < 0.0001). Multiple logistic regression analyses showed that END was positively associated with diabetes mellitus, hs-CRP level and NIHSS score on admission, and negatively associated with the EPA/AA ratio (odds ratio, OR: 0.18; 95% confidence interval, CI: 0.05-0.58; p = 0.003), DHA/AA ratio (OR: 0.045; 95% CI: 0.006-0.30; p = 0.001), EPA+DHA/AA ratio (OR: 0.45; 95% CI: 0.26-0.74; p = 0.002) and diagnosis of small vessel disease. Conclusions: Our data suggest that a low serum n-3 PUFA/n-6 PUFA ratio on admission may predict neurological deterioration in Japanese patients with acute ischemic stroke. Large-scale prospective studies are further required to clarify the role of PUFAs in the acute phase of ischemic stroke.",arachidonic acid;C reactive protein;docosahexaenoic acid;icosapentaenoic acid;aged;article;brain ischemia;brain region;capillary gas chromatography;computer assisted tomography;diabetes mellitus;diffusion weighted imaging;fatty acid blood level;female;human;ischemic heart disease;Japanese (people);major clinical study;male;mental deterioration;National Institutes of Health Stroke Scale;neuroimaging;nuclear magnetic resonance imaging;prediction;priority journal;retrospective study,"Suda, S.;Katsumata, T.;Okubo, S.;Kanamaru, T.;Suzuki, K.;Watanabe, Y.;Katsura, K. I.;Katayama, Y.",2013,,,0,
1041,Brain tissue segmentation using fuzzy clustering techniques,"BACKGROUND: Medical image segmentation is an essential step for most consequent image analysis tasks. Medical images can be segmented manually, but the accuracy of image segmentation using the automated segmentation algorithms is more when compared with the manual calculations. In this paper, an automated segmentation and classification of tissues are proposed for MR brain images. OBJECTIVE: To classify MR brain image into three segments such as Grey Matter (GM), White Matter (WM) and Cerebro-Spinal Fluid (CSF). Classification of brain into tissues helps to diagnose several diseases such as tumors, Alzheimer's disease, stroke, multiple sclerosis. METHODS: An unsupervised clustering technique such as Fuzzy C-Means (FCM) algorithm has been widely used in segmenting the images. The spatial information is not fully utilized by the conventional clustering algorithm and hence it is not applicable for clustering a noisy image. We incorporate a method for image clustering called out as Reformulated Fuzzy Local information C-Means Clustering algorithm [RFLICM] which is a variant of traditional Clustering algorithm by considering both spatial and gray level information. In RFLICM, spatial distance is replaced by local coefficient of variation in a fuzzy manner. RESULTS: Experiments are conducted on brain images to validate the performance of the proposed technique in segmenting the medical images and the efficiency achieved in the presence of salt and pepper noise is 99.86%. CONCLUSION: Standard FCM, Fuzzy Local information C-means clustering algorithm [FLICM], Reformulated Fuzzy Local information C-means clustering algorithm [RFLICM] are compared to explore the accuracy of our proposed approach. Clustering results show that RFLICM segmentation method is appropriate for classifying tissues in brain MR image.",,"Sucharitha, M.;Geetha, K. P.",2015,,10.3233/thc-151012,0,
1042,Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa,"Rett syndrome (RS), a neurodevelopmental disorder of unknown etiology occurring almost exclusively in females, is characterized by autistic-like behavior, motor dysfunction, loss of language skills, dementia, and microcephaly. This study is a follow-up and extension of a previously reported neuroimaging study of patients with RS. We replicated previously reported findings with a larger patient population, and the volumetric MRI analysis was extended to include an analysis of neuroanatomy of the posterior fossa. Twenty girls with RS were compared with individually age- and gender-matched normal controls. Patients with RS showed global reduction in gray- and white-matter volumes. The prefrontal, posterior-frontal, and anterior-temporal regions showed the largest bilateral decrease in gray-matter volume, whereas white-matter volume was uniformly reduced throughout the brain. We found confirmation for the preferential reduction in caudate nucleus volume. However, we observed no preferential reduction in midbrain volume despite a preferential reduction in the midsagittal area of this region. We also present an individual case comparison between monozygotic twins discordant for RS.","Adolescent;Adult;Cerebral Cortex/*pathology;Cerebrospinal Fluid;Child;Child, Preschool;Cranial Fossa, Posterior/*pathology;Diseases in Twins;Female;Humans;Male;Rett Syndrome/*pathology;Twins, Monozygotic","Subramaniam, B.;Naidu, S.;Reiss, A. L.",1997,Feb,,0,
1043,Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group,"Amyloid imaging plays an important role in the research and diagnosis of dementing disorders. Substantial variation in quantitative methods to measure brain amyloid burden exists in the field. The aim of this work is to investigate the impact of methodological variations to the quantification of amyloid burden using data from the Dominantly Inherited Alzheimer's Network (DIAN), an autosomal dominant Alzheimer's disease population. Cross-sectional and longitudinal [11C]-Pittsburgh Compound B (PiB) PET imaging data from the DIAN study were analyzed. Four candidate reference regions were investigated for estimation of brain amyloid burden. A regional spread function based technique was also investigated for the correction of partial volume effects. Cerebellar cortex, brain-stem, and white matter regions all had stable tracer retention during the course of disease. Partial volume correction consistently improves sensitivity to group differences and longitudinal changes over time. White matter referencing improved statistical power in the detecting longitudinal changes in relative tracer retention; however, the reason for this improvement is unclear and requires further investigation. Full dynamic acquisition and kinetic modeling improved statistical power although it may add cost and time. Several technical variations to amyloid burden quantification were examined in this study. Partial volume correction emerged as the strategy that most consistently improved statistical power for the detection of both longitudinal changes and across-group differences. For the autosomal dominant Alzheimer's disease population with PiB imaging, utilizing brainstem as a reference region with partial volume correction may be optimal for current interventional trials. Further investigation of technical issues in quantitative amyloid imaging in different study populations using different amyloid imaging tracers is warranted.",,"Su, Y.;Blazey, T. M.;Owen, C. J.;Christensen, J. J.;Friedrichsen, K.;Joseph-Mathurin, N.;Wang, Q.;Hornbeck, R. C.;Ances, B. M.;Snyder, A. Z.;Cash, L. A.;Koeppe, R. A.;Klunk, W. E.;Galasko, D.;Brickman, A. M.;McDade, E.;Ringman, J. M.;Thompson, P. M.;Saykin, A. J.;Ghetti, B.;Sperling, R. A.;Johnson, K. A.;Salloway, S. P.;Schofield, P. R.;Masters, C. L.;Villemagne, V. L.;Fox, N. C.;Forster, S.;Chen, K.;Reiman, E. M.;Xiong, C.;Marcus, D. S.;Weiner, M. W.;Morris, J. C.;Bateman, R. J.;Benzinger, T. L.",2016,,10.1371/journal.pone.0152082,0,
1044,White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment,"OBJECTIVE: Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment. DESIGN: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits. METHODS: We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions. RESULTS: HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4 cell count below 500 cells/mul, but not with HIV-associated cognitive deficits. CONCLUSION: Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits. VIDEO ABSTRACT: .",0 (Anti-HIV Agents);AIDS Dementia Complex/epidemiology;Anti-HIV Agents/ therapeutic use;Diffusion Tensor Imaging;HIV Infections/ complications/ drug therapy/virology;HIV-1/ isolation & purification;Humans;Leukoencephalopathies/complications/ epidemiology/ pathology;Male;Middle Aged;White Matter/ pathology,"Su, T.;Caan, M. W.;Wit, F. W.;Schouten, J.;Geurtsen, G. J.;Cole, J. H.;Sharp, D. J.;Vos, F. M.;Prins, M.;Portegies, P.;Reiss, P.;Majoie, C. B.;Study, A. GEhIV Cohort",2016,Jan,,0,
1045,Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency,"BACKGROUND: Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B12 deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. OBSERVATION: A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B12 deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B12 supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. CONCLUSION: Leukoencephalopathy and dementia should raise the suspicion of a vitamin B12 deficiency because vitamin B12 supplementation may result in at least partial clinical improvement.",,"Su, S.;Libman, R. B.;Diamond, A.;Sharfstein, S.",2000,May-Jun,10.1053/jscd.2000.5869,0,
1046,A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers,"Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts.",Adult;Analysis of Variance;Aspartic Acid/analogs & derivatives/metabolism;Biomarkers/ metabolism;Brain/ metabolism;Cross-Sectional Studies;Female;Humans;Huntington Disease/ metabolism/ pathology;Inositol/metabolism;Longitudinal Studies;Magnetic Resonance Spectroscopy;Male;Middle Aged;Putamen/pathology;Statistics as Topic;Time Factors;White Matter/pathology,"Sturrock, A.;Laule, C.;Wyper, K.;Milner, R. A.;Decolongon, J.;Dar Santos, R.;Coleman, A. J.;Carter, K.;Creighton, S.;Bechtel, N.;Bohlen, S.;Reilmann, R.;Johnson, H. J.;Hayden, M. R.;Tabrizi, S. J.;Mackay, A. L.;Leavitt, B. R.",2015,Mar,10.1002/mds.26118,0,
1047,Accurate template-based correction of brain MRI intensity distortion with application to dementia and aging,"This paper examines an alternative approach to separating magnetic resonance imaging (MRI) intensity inhomogeneity from underlying tissue-intensity structure using a direct template-based paradigm. This permits the explicit spatial modeling of subtle intensity variations present in normal anatomy which may confound common retrospective correction techniques using criteria derived from a global intensity model. A fine-scale entropy driven spatial normalisation procedure is employed to map intensity distorted MR images to a tissue reference template. This allows a direct estimation of the relative bias field between template and subject MR images, from the ratio of their low-pass filtered intensity values. A tissue template for an aging individual is constructed and used to correct distortion in a set of data acquired as part of a study on dementia. A careful validation based on manual segmentation and correction of nine datasets with a range of anatomies and distortion levels is carried out. This reveals a consistent improvement in the removal of global intensity variation in terms of the agreement with a global manual bias estimate, and in the reduction in the coefficient of intensity variation in manually delineated regions of white matter.","Aging;Algorithms;Alzheimer Disease/ diagnosis/pathology;Brain/ pathology;Computer Simulation;Dementia/diagnosis/pathology;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Models, Biological;Pattern Recognition, Automated;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Studholme, C.;Cardenas, V.;Song, E.;Ezekiel, F.;Maudsley, A.;Weiner, M.",2004,Jan,10.1109/tmi.2003.820029,0,
1048,Deformation tensor morphometry of semantic dementia with quantitative validation,"High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.","Aged;Atrophy;Brain/*pathology;Brain Mapping;Cerebral Cortex/pathology;Dementia/*diagnosis;Dominance, Cerebral/physiology;Female;Humans;*Image Enhancement;*Image Processing, Computer-Assisted;*Imaging, Three-Dimensional;Linear Models;*Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Reference Values;Reproducibility of Results","Studholme, C.;Cardenas, V.;Blumenfeld, R.;Schuff, N.;Rosen, H. J.;Miller, B.;Weiner, M.",2004,Apr,10.1016/j.neuroimage.2003.12.009,0,
1049,Dense feature deformation morphometry: Incorporating DTI data into conventional MRI morphometry,"Registration based mapping of geometric differences in MRI anatomy allows the detection of subtle and complex changes in brain anatomy over time that provides an important quantitative window on the process of both brain development and degeneration. However, methods developed for this have so far been aimed at using conventional structural MRI data (T1W imaging) and the resulting maps are limited in their ability to localize patterns of change within sub-regions of uniform tissue. Alternative MRI contrast mechanisms, in particular Diffusion Tensor Imaging (DTI) data are now more commonly being used in serial studies and provide valuable complementary microstructural information within white matter. This paper describes a new approach which incorporates information from DTI data into deformation tensor morphometry of conventional MRI. The key problem of using the additional information provided by DTI data is addressed by proposing a novel mutual information (MI) derived criterion termed diffusion paired MI. This combines conventional and diffusion data in a single registration measure. We compare different formulations of this measure when used in a diffeomorphic fluid registration scheme to map local volume changes. Results on synthetic data and example images from clinical studies of neurodegenerative conditions illustrate the improved localization of tissue volume changes provided by the incorporation of DTI data into the morphometric registration. © 2008 Elsevier B.V. All rights reserved.",,"Studholme, C.",2008,December,,0,
1050,Incorporating DTI data as a constraint in deformation tensor morphometry between T1 MR images,"Deformation tensor morphometry provides a sensitive approach to detecting and mapping subtle volume changes in the brain from conventional high resolution T1W MRI data. However, it is limited in its ability to localize volume changes within sub-regions of uniform white matter in T1W MRI. In contrast, lower resolution DTI data provides valuable complementary microstructural information within white matter. An approach to incorporating information from DTI data into deformation tensor morphometry of conventional high resolution T1W imaging is described. A novel mutual information (MI) derived criteria is proposed, termed diffusion paired MI, using an approximation to collective many-channel MI between all images. This approximation avoids the evaluation of high dimensional joint probability distributions, but allows a combination of conventional and diffusion data in a single registration criteria. The local gradient of this measure is used to drive a viscous fluid registration between repeated DTI-MRI imaging studies. Results on example data from clinical studies of Alzheimer's disease illustrate the improved localization of tissue loss patterns within regions of white matter.","Algorithms;Alzheimer Disease/ pathology;Artificial Intelligence;Brain/ pathology;Databases, Factual;Diffusion Magnetic Resonance Imaging/ methods;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Information Storage and Retrieval/methods;Nerve Fibers, Myelinated/ pathology;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Studholme, C.",2007,,,0,
1051,Ischemic infarct involving all arterial territories of the thalamus,Ischemic infarcts of the thalamus involve one or two of its four arterial territories that are usually supplied by the posterior cerebral (PCA) and the posterior communicating (PCoA) arteries. We report a patient who suffered ischemic infarcts in all arterial territories of the right thalamus. Magnetic resonance (MR) angiography showed an occlusion of the right PCA and failed to visualize a PCoA. We assume that the absence of a relevant thalamic blood supply deriving from the PCoA enabled PCA occlusion to cause infarcts in all thalamic territories.,acetylsalicylic acid;cholesterol;high density lipoprotein cholesterol;adult;anxiety;aorta;apathy;artery occlusion;article;ataxia;atherosclerotic plaque;blood analysis;brain artery;brain blood flow;brain infarction;brain ischemia;brain region;case report;cerebral artery disease;cholesterol blood level;smoking;cognitive defect;depression;diet;Doppler echography;electrocardiogram;error;heart left ventricle hypertrophy;Holter monitoring;homonymous hemianopia;human;hypesthesia;hypoalgesia;learning;lipid analysis;magnetic resonance angiography;male;medial geniculate body;neurologic examination;nuclear magnetic resonance imaging;paresthesia;perimetry;posterior cerebral artery;pulvinar;recall;right hemisphere;cerebrovascular accident;thalamus;thalamus dorsomedial nucleus;thinking;thorax radiography;transesophageal echocardiography;transthoracic echocardiography;verbal behavior;vision;aspirin,"Studer, A.;Georgiadis, D.;Baumgartner, R. W.",2003,,,0,
1052,Early microstructural white matter changes in patients with HIV: A diffusion tensor imaging study,Background: Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV).Methods: We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests.Results: Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had,,"Stubbe-Drger, B.;Deppe, M.;Mohammadi, S.;Keller, S. S.;Kugel, H.;Gregor, N.;Evers, S.;Young, P.;Ringelstein, E. B.;Arendt, G.;Knecht, S.;Husstedt, I. W.",2012,,,0,
1053,In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice,"We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/alpha-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [(15)O]-H2O positron emission tomography. Glucose metabolism ([(18)F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia.","IY9XDZ35W2 (Glucose);Animals;Brain/ blood supply/diagnostic imaging/metabolism/ pathology;Brain Ischemia/diagnostic imaging/metabolism/ pathology;Carotid Artery, Common/diagnostic imaging/metabolism/ pathology;Cerebrovascular Circulation;Diffusion Magnetic Resonance Imaging/methods;Disease Models, Animal;Glucose/metabolism;Magnetic Resonance Angiography/methods;Male;Mice;Mice, Inbred C57BL;Positron-Emission Tomography/methods;Vascular Remodeling;Arterial spin labeling;Cbf;acute stroke;animal models;positron emission tomography","Struys, T.;Govaerts, K.;Oosterlinck, W.;Casteels, C.;Bronckaers, A.;Koole, M.;Van Laere, K.;Herijgers, P.;Lambrichts, I.;Himmelreich, U.;Dresselaers, T.",2017,Feb,,0,1054
1054,In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice,"We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/alpha-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [15O]-H2O positron emission tomography. Glucose metabolism ([18F]-FDG positron emission tomography) or white matter organization (diffusion-weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia.",,"Struys, T.;Govaerts, K.;Oosterlinck, W.;Casteels, C.;Bronckaers, A.;Koole, M.;Van Laere, K.;Herijgers, P.;Lambrichts, I.;Himmelreich, U.;Dresselaers, T.",2016,Mar 18,10.1177/0271678x16638349,0,
1055,Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?,"The purpose of this explorative study was to investigate whether diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameter changes are reliable measures of white matter integrity changes in Alzheimer's disease (AD) patients using a whole brain voxel-based analysis (VBA). Therefore, age- and gender-matched patients with mild cognitive impairment (MCI) due to AD (n = 18), dementia due to AD (n = 19), and age-matched cognitively healthy controls (n = 14) were prospectively included. The magnetic resonance imaging protocol included routine structural brain imaging and DKI. Datasets were transformed to a population-specific atlas space. Groups were compared using VBA. Differences in diffusion and mean kurtosis measures between MCI and AD patients and controls were shown, and were mainly found in the splenium of the corpus callosum and the corona radiata. Hence, DTI and DKI parameter changes are suggestive of white matter changes in AD.",,"Struyfs, H.;Van Hecke, W.;Veraart, J.;Sijbers, J.;Slaets, S.;De Belder, M.;Wuyts, L.;Peters, B.;Sleegers, K.;Robberecht, C.;Van Broeckhoven, C.;De Belder, F.;Parizel, P. M.;Engelborghs, S.",2015,,10.3233/jad-150253,0,
1056,Vascular dementia,"Many cases of age-related cognitive dementia are caused by cerebrovascular lesions, and various vascular syndromes can lead to cognitive impairment and dementia. Repeated cortical infarcts due to embolic disease of the heart or major cerebral vessels can cause progressive deterioration towards dementia and incapacitation. In classic multi-infarct dementia, cognitive deterioration is stepwise rather than smoothly progressive. While diagnostic technologies have vastly improved and added to general knowledge of the pathology of cerebrovascular disease, MRI, PET, and transcranial Doppler scans have demonstrated that significant white matter change is possible without clinically recognized TIA or completed stroke. In addition, patients may have initial complaints that are not serious enough to produce changes on mental status examination. Many patients have mixed dementia, exhibiting aspects of both degenerative brain disease and clinical evidence of strokes or significant changes on MRI scan. The overlap between vascular and degenerative disease is significant, yet the exact interaction of the pathophysiology of the vascular lesions and the degenerative changes is not known. The treatment of vascular or mixed dementia involves control of the risk factors for continued vascular events and treatment with the cholinesterase inhibitors.",,"Strub, R. L.",2003,Winter,,0,
1057,Structural and metabolic brain abnormalities in preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy,"OBJECTIVE: To assess, by using quantitative MRI metrics, structural and metabolic brain abnormalities in subjects with preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). BACKGROUND: Brain MRI abnormalities have been occasionally reported in preclinical CADASIL subjects. However, very little is known as to when the brain tissue damage starts to accumulate, what brain regions are primarily involved and whether the brain damage is significant in subjects who have no overt clinical manifestations of the disease. METHODS: Twelve subjects (mean age 40 years; range 26-55 years; males/females 6/6) with genetically proven CADASIL and no clinical signs of the disease underwent conventional MRI and proton MR spectroscopic imaging ((1)H-MRSI) to measure white matter (WM) lesion volume (LV), global and regional cerebral volumes, and WM levels of N-acetylaspartate (NAA) normalised to creatine (Cr). MR values were compared with those of 13 age- and sex-matched healthy controls. RESULTS: All preclinical CADASIL showed WM lesions (range 0.2 to 26 cm(3)). They were mostly distributed in the frontal and parietal regions, with the highest probability in the corona radiata. On (1)H-MRSI examination, NAA/Cr values were lower in preclinical CADASIL than in HC, particularly in the corona radiata (p<0.01). Normalised brain and cortical volumes were also lower in preclinical CADASIL than in HC (p<0.01), particularly in the frontal cortex. CONCLUSIONS: The pathological process occurring in CADASIL leads to damage of WM and neocortex much before the evidence of clinical symptoms. At this preclinical stage, this seems to take place prevalently in the frontal brain region.",Adult;Age Factors;Aspartic Acid/analogs & derivatives/metabolism;CADASIL/ metabolism/ pathology;Cerebral Infarction/ metabolism/ pathology;Creatine/metabolism;Female;Frontal Lobe/metabolism/pathology;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Protons,"Stromillo, M. L.;Dotti, M. T.;Battaglini, M.;Mortilla, M.;Bianchi, S.;Plewnia, K.;Pantoni, L.;Inzitari, D.;Federico, A.;De Stefano, N.",2009,Jan,10.1136/jnnp.2008.155853,0,
1058,Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis,"The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/ pathology;Neural Pathways/ pathology","Stricker, N. H.;Schweinsburg, B. C.;Delano-Wood, L.;Wierenga, C. E.;Bangen, K. J.;Haaland, K. Y.;Frank, L. R.;Salmon, D. P.;Bondi, M. W.",2009,Mar 1,10.1016/j.neuroimage.2008.11.027,0,
1059,Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum,"Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC.",,"Stricker, N. H.;Salat, D. H.;Kuhn, T. P.;Foley, J. M.;Price, J. S.;Westlye, L. T.;Esterman, M. S.;McGlinchey, R. E.;Milberg, W. P.;Leritz, E. C.",2016,Feb,10.1177/1533317515578257,0,
1060,Decreased white matter integrity in neuropsychologically defined mild cognitive impairment is independent of cortical thinning,"Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for corticalthic kness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes.","Adult;Aged;Apolipoproteins E/genetics;Cerebral Cortex/ pathology;Diffusion Magnetic Resonance Imaging;Executive Function;Factor Analysis, Statistical;Female;Genotype;Humans;Image Processing, Computer-Assisted;Male;Memory;Middle Aged;Mild Cognitive Impairment/genetics/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Stricker, N. H.;Salat, D. H.;Foley, J. M.;Zink, T. A.;Kellison, I. L.;McFarland, C. P.;Grande, L. J.;McGlinchey, R. E.;Milberg, W. P.;Leritz, E. C.",2013,Sep,10.1017/s1355617713000660,0,
1061,Investigating structural brain changes of dehydration using voxel-based morphometry,"Dehydration can affect the volume of brain structures, which might imply a confound in volumetric and morphometric studies of normal or diseased brain. Six young, healthy volunteers were repeatedly investigated using three-dimensional T(1)-weighted magnetic resonance imaging during states of normal hydration, hyperhydration, and dehydration to assess volume changes in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). The datasets were analyzed using voxel-based morphometry (VBM), a widely used voxel-wise statistical analysis tool, FreeSurfer, a fully automated volumetric segmentation measure, and SIENAr a longitudinal brain-change detection algorithm. A significant decrease of GM and WM volume associated with dehydration was found in various brain regions, most prominently, in temporal and sub-gyral parietal areas, in the left inferior orbito-frontal region, and in the extra-nuclear region. Moreover, we found consistent increases in CSF, that is, an expansion of the ventricular system affecting both lateral ventricles, the third, and the fourth ventricle. Similar degrees of shrinkage in WM volume and increase of the ventricular system have been reported in studies of mild cognitive impairment or Alzheimer's disease during disease progression. Based on these findings, a potential confound in GM and WM or ventricular volume studies due to the subjects' hydration state cannot be excluded and should be appropriately addressed in morphometric studies of the brain.",Adult;Body Weight;Brain/ pathology;Cerebral Ventricles/pathology;Cluster Analysis;Dehydration/cerebrospinal fluid/ pathology/urine;Drinking;Female;Humans;Male;Organ Size;Urination,"Streitburger, D. P.;Moller, H. E.;Tittgemeyer, M.;Hund-Georgiadis, M.;Schroeter, M. L.;Mueller, K.",2012,,10.1371/journal.pone.0044195,0,
1062,Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia,"BACKGROUND: White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear. METHODS: Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression. RESULTS: 55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value < 0.001). Correcting for medial temporal lobe atrophy or the presence of lacunes did not change statistical significance. CONCLUSION: PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.","Alzheimer Disease [drug therapy] [pathology];Amnesia [drug therapy] [pathology];Antioxidants [therapeutic use];Atrophy;Brain [drug effects] [pathology];Cerebral Ventricles [drug effects] [pathology];Cholinesterase Inhibitors [therapeutic use];Cognition Disorders [drug therapy] [pathology];Dementia [drug therapy] [pathology];Disease Progression;Double-Blind Method;Image Processing, Computer-Assisted [methods];Indans [therapeutic use];Magnetic Resonance Imaging [methods];Piperidines [therapeutic use];Prospective Studies;Temporal Lobe [drug effects] [pathology];Time Factors;Treatment Outcome;Vitamin E [therapeutic use];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Straaten, E. C.;Harvey, D.;Scheltens, P.;Barkhof, F.;Petersen, R. C.;Thal, L. J.;Jack, C. R.;DeCarli, C.",2008,,10.1007/s00415-008-0874-y,0,
1063,Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type,"OBJECTIVE: To examine associations between dementia severity and quantitative magnetic resonance imaging measures of cortical gray matter volume and abnormal white matter volume in 52 patients diagnosed with probable Alzheimer disease. DESIGN: Analysis of the relationship between magnetic resonance imaging volume measures and dementia severity using multiple regression and Pearson correlations. SETTING: Alzheimer's Disease Research Center, University of California, San Diego. PARTICIPANTS: Twenty-three men and 29 women with probable Alzheimer disease (average age, 71.7 years; average education, 13.3 years). MAIN OUTCOME MEASURES: The Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination. RESULTS: Using simultaneous multiple regression, magnetic resonance imaging volumetric measures of cortical gray matter and abnormal white matter were independently associated with dementia severity measured by either the MDRS or the Mini-Mental State Examination. Cortical gray matter volume and abnormal white matter volume also made independent contributions to performance in 4 of 5 cognitive domains assessed by the MDRS. Regional analysis indicated that limbic cortical gray matter volume and nonlimbic cortical gray matter volume were also correlated with the MDRS score; however, in the regression analysis the individual gray matter measures were not independently associated with MDRS performance. A similar analysis revealed statistically independent relationships of limbic gray matter volume and abnormal white matter volume, but not nonlimbic cortical gray matter volume, to Mini-Mental State Examination performance. CONCLUSIONS: Quantitative magnetic resonance methods provided strong evidence that cortical gray matter volume, which may reflect atrophy, and abnormal white matter volume are independently related to dementia severity in probable Alzheimer disease: lower gray matter and higher abnormal white matter volumes are associated with more severe dementia.",Aged;Alzheimer Disease/ pathology/ psychology;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests,"Stout, J. C.;Jernigan, T. L.;Archibald, S. L.;Salmon, D. P.",1996,Aug,,0,
1064,Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease,"The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer's disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate, in vivo, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (i) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (ii) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Amnesia/ pathology/physiopathology;Atrophy/pathology;Brain Mapping;Female;Hippocampus/ pathology/physiopathology;Humans;Magnetic Resonance Imaging/methods;Male;Memory;Nerve Fibers/ pathology","Stoub, T. R.;deToledo-Morrell, L.;Stebbins, G. T.;Leurgans, S.;Bennett, D. A.;Shah, R. C.",2006,Jun 27,10.1073/pnas.0603414103,0,
1065,Parahippocampal white matter volume predicts Alzheimer's disease risk in cognitively normal old adults,"An in vivo marker of the underlying pathology in Alzheimer's disease (AD) is atrophy in select brain regions detected with quantitative magnetic resonance imaging (MRI). Although gray matter changes have been documented to be predictive of cognitive decline culminating in AD among healthy older adults, very little attention has been given to alterations in white matter as a possible MRI biomarker predictive of AD. In this investigation, we examined parahippocampal white matter (PWM) volume derived from baseline MRI scans in 2 independent samples of 65 cognitively normal older adults, followed longitudinally, to determine if it was predictive of AD risk. The average follow-up period for the 2 samples was 8.5 years. Comparisons between the stable participants (N = 50) and those who declined to AD (N = 15) over time revealed a significant difference in baseline PWM volume (p < 0.001). Furthermore, baseline PWM volume was predictive not only of time to AD (hazard ratio = 3.1, p < 0.05), but also of baseline episodic memory performance (p = 0.041). These results demonstrate that PWM atrophy provides a sensitive MRI biomarker of AD dementia risk among those with normal cognitive function.",Aged;Alzheimer Disease/diagnosis/ pathology/psychology;Atrophy;Biomarkers;Cognition;Female;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging;Male;Organ Size;Risk;White Matter/ pathology,"Stoub, T. R.;Detoledo-Morrell, L.;Dickerson, B. C.",2014,Aug,10.1016/j.neurobiolaging.2014.01.153,0,
1066,Age-related changes in the mesial temporal lobe: the parahippocampal white matter region,"The perforant pathway originates from cells in the entorhinal cortex and relays sensory information from the neocortex to the hippocampus, a region critical for memory function. Imaging studies have demonstrated structural alterations in the parahippocampal white matter in the region of the perforant pathway in people at risk for developing Alzheimer's disease. It is not clear, however, if changes noted in this region are indicative of pathological aging or are a function of the normal aging process. We compared magnetic resonance imaging (MRI)-derived mesial temporal lobe volumes in 51 healthy older individuals and 40 young participants, with an emphasis on the parahippocampal white matter. Yearly clinical evaluations showed that 9 of the older cohort declined in cognitive function. Parahippocampal white matter, hippocampal, and entorhinal cortex volumes were significantly reduced in healthy older people who remained stable over time compared with young participants. These findings suggest that volume differences in mesial temporal lobe gray and white matter structures may take place as a result of the normative aging process.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Cohort Studies;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Nerve Fibers, Myelinated/ pathology;Organ Size;Parahippocampal Gyrus/ pathology;Temporal Lobe/ pathology;Young Adult","Stoub, T. R.;Barnes, C. A.;Shah, R. C.;Stebbins, G. T.;Ferrari, C.;deToledo-Morrell, L.",2012,Jul,10.1016/j.neurobiolaging.2011.02.010,0,
1067,Divry-Van Bogaert syndrome in a female: Relationship to Sneddon's syndrome and radiographic appearances,"A 28-year-old woman presented with generalised livedo reticularis, dementia, epilepsy, and pyramidal and extrapyramidal signs. Multiple focal infarcts were seen on MRI. Angiography demonstrated widespread cerebromeningeal angiomatosis with multiple small and medium size arterial occlusions. A lifelong personal and family history of mental handicap in the absence of anticardiolipin antibodies suggests Divry-Van Bogaert syndrome, not previously been reported in a female. Similarities to Sneddon's syndrome are discussed.",calcium channel blocking agent;cardiolipin antibody;adrenoleukodystrophy;adult;anamnesis;article;brain infarction;brain radiography;case report;clinical feature;dementia;epilepsy;essential hypertension;extrapyramidal system;family history;female;hemangiomatosis;human;livedo reticularis;mental deficiency;moyamoya disease;nuclear magnetic resonance imaging;occlusive cerebrovascular disease;priority journal;pyramidal tract;Sneddon syndrome,"Stone, J.;Bhattacharya, J.;Walls, T. J.",2001,,,0,
1068,Contrasting gray and white matter changes in preclinical Huntington disease: an MRI study,"BACKGROUND: In Huntington disease (HD), substantial striatal atrophy precedes clinical motor symptoms. Accordingly, neuroprotection should prevent major cell loss before such symptoms arise. To evaluate neuroprotection, biomarkers such as MRI measures are needed. This requires first establishing the best imaging approach. METHODS: Using a cross-sectional design, we acquired T1-weighted and diffusion-weighted scans in 39 preclinical (pre-HD) individuals and 25 age-matched controls. T1-weighted scans were analyzed with gross whole-brain segmentation and voxel-based morphometry. Analysis of diffusion-weighted scans used skeleton-based tractography. For all imaging measures, we compared pre-HD and control groups and within the pre-HD group we examined correlations with estimated years to clinical onset. RESULTS: Pre-HD individuals had lower gross gray matter (GM) and white matter (WM) volume. Voxel-wise analysis demonstrated local GM volume loss, most notably in regions consistent with basal ganglia-thalamocortical pathways. By contrast, pre-HD individuals showed widespread reductions in WM integrity, probably due to a loss of axonal barriers. Both GM and WM imaging measures correlated with estimated years to onset. CONCLUSIONS: Using automated, observer-independent methods, we found that GM loss in pre-HD was regionally specific, while WM deterioration was much more general and probably the result of demyelination rather then axonal degeneration. These findings provide important information about the nature, relative staging, and topographic specificity of brain changes in pre-HD and suggest that combining GM and WM imaging may be the best biomarker approach. The empirically derived group difference images from this study are provided as regions-of-interest masks for improved sensitivity in future longitudinal studies.","Adult;Brain/ pathology;Brain Mapping;Chi-Square Distribution;Cross-Sectional Studies;Female;Humans;Huntington Disease/ pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Fibers, Unmyelinated/ pathology","Stoffers, D.;Sheldon, S.;Kuperman, J. M.;Goldstein, J.;Corey-Bloom, J.;Aron, A. R.",2010,Apr 13,10.1212/WNL.0b013e3181d8c20a,0,
1069,Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene,"A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto's encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient's neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene.",Arylsulfatase A;early onset dementia;genetic testing;late-onset metachromatic leukodystrophy,"Stoeck, K.;Psychogios, M. N.;Ohlenbusch, A.;Steinfeld, R.;Schmidt, J.",2016,Feb 6,10.3233/jad-150819,0,
1070,"Brain SPECT: a controlled, blinded assessment of intra-reader and inter-reader agreement","A detailed assessment of intra- and inter-reader variation in the interpretation of brain SPECT scans has been performed. A random sample was selected from scans performed at a community/teaching hospital in Seattle. Scans were interpreted independently by three experienced readers who were blinded to all patient information. Forty-eight scans were interpreted twice by each reader, for a total of 288 readings. Readers recorded detailed assessments of individual lesions and overall impressions using a standardized reporting form. Intra-observer agreement as reflected in per cent agreement for severity scores ranged from 65% to 100%. Intra-observer agreement on the 'overall impression' was very good for Alzheimer's pattern (kappa=0.73-1.00), and fair to good for the 'heterogeneous pattern' (kappa=0.30-0.63). Inter-observer agreement, as reflected in per cent agreement, ranged from 29% to 100%. Inter-observer agreement about the 'overall impression' was fair to moderate for Alzheimer's pattern (kappa=0.24-0.54) and was poor for the descriptors 'heterogeneous' and 'normal'. It is concluded that brain SPECT has great potential value in many important conditions. This study demonstrates a need for further work in the areas of pattern definition and reduction of observer variation.","Alzheimer Disease [radionuclide imaging];Brain [radionuclide imaging];Brain Diseases [radionuclide imaging];Cognition Disorders [radionuclide imaging];Dementia [radionuclide imaging];Dementia, Multi-Infarct [radionuclide imaging];Double-Blind Method;Nuclear Medicine [standards];Observer Variation;Reproducibility of Results;Retrospective Studies;Sensitivity and Specificity;Tomography, Emission-Computed, Single-Photon [methods] [statistics & numerical data];Adult[checkword];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Stockbridge, H. L.;Lewis, D.;Eisenberg, B.;Lee, M.;Schacher, S.;Belle, G.;Keifer, M.;Brodkin, C. A.;Buchwald, D.",2002,,,0,
1071,Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease,"Phase-contrast magnetic resonance imaging (PC-MRI) or flow-sensitive MRI can be used to noninvasively measure intracranial vascular and CSF flow. Monro-Kellie homeostasis is the complex compensatory mechanism for the increase in intracranial blood volume during systole. Through PC-MRI techniques, our understanding of Monro-Kellie homeostasis and the associated intracranial hydrodynamics has greatly improved. Failure of this homeostatic mechanism has been implicated in a wide range of cerebral disorders, including vascular and Alzheimer's dementia, late-onset depression, benign and secondary intracranial hypertension, communicating and normal pressure hydrocephalus, and age-related white matter changes. The most common mode of homeostatic failure is due to vascular disease with decreased cerebral arterial compliance. This has wide-reaching implications in the investigation of patients with cerebral vascular disease. Here we discuss the role of PC-MRI in the study of cerebral hydrodynamics and the current understanding of Monro-Kellie homeostasis in both healthy and disease states. Quantitative assessment of the changes in this homeostatic mechanism using PC-MRI has important implications in the development of biomarkers of vascular involvement in disease with application in diagnosis, treatment planning, phenotype identification, and outcome assessment in clinical trials. © 2007 The American Society for Experimental NeuroTherapeutics, Inc.",,"Stivaros, S. M.;Jackson, A.",2007,July,,0,
1072,White matter abnormalities and memory in Alzheimer's disease [6] (multiple letters),,Alzheimer disease;amnesia;amygdaloid nucleus;brain atrophy;brain size;cognitive defect;disease severity;earthquake;emotion;human;letter;nuclear magnetic resonance imaging;white matter,"Stewart, R. J.;Ikeda, M.;Mori, E.",1998,,,0,
1073,White matter abnormalities and memory in Alzheimer's disease,,Alzheimer Disease/complications/*pathology;Brain Diseases/*pathology;Humans;Magnetic Resonance Imaging;Memory Disorders/*pathology,"Stewart, R. J.",1998,Sep,,0,
1074,Longitudinal neuroimaging correlates of subjective memory impairment: 4-year prospective community study,"BACKGROUND: Complaints about memory are common in older people but their relationship with underlying brain changes is controversial. AIMS: To investigate the relationship between subjective memory impairment and previous or subsequent changes in white matter lesions and brain volumes. METHOD: In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up. RESULTS: Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms - associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) epsilon4 allele and in those without baseline subjective memory impairment. CONCLUSIONS: Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.","Aged;Aged, 80 and over;Apolipoproteins E/genetics;Brain/ pathology;Cerebrospinal Fluid/physiology;Cognition Disorders/epidemiology/pathology/psychology;Dementia/epidemiology/ pathology/psychology;Depression/epidemiology;Diagnostic Self Evaluation;Disease Progression;Epidemiologic Methods;Female;France/epidemiology;Hippocampus/pathology;Humans;Magnetic Resonance Imaging/ methods;Male;Memory Disorders/epidemiology/ pathology/psychology;Neuropsychological Tests;Psychiatric Status Rating Scales","Stewart, R.;Godin, O.;Crivello, F.;Maillard, P.;Mazoyer, B.;Tzourio, C.;Dufouil, C.",2011,Mar,10.1192/bjp.bp.110.078683,0,
1075,Neuroimaging correlates of subjective memory deficits in a community population,"BACKGROUND: Subjective memory deficit (SMD) is one of few potential presenting symptoms for people with early cognitive impairment. However, associations with underlying brain changes are unclear. METHODS: In a community sample of 1,779 people without dementia, and with neuroimaging (MRI) data, associations were investigated for SMD with white matter lesion volume and with the following volumetric measures: gray and white matter, CSF, hippocampal, parahippocampal, and amygdalar. Covariates included depressive symptoms (Center for Epidemiologic Studies Depression Scale), a battery of cognitive tests, physical health, and social activity. RESULTS: SMD was present in 26.4% of the sample. Of the neuroimaging measures analyzed, SMD was most strongly associated with temporal WML (OR for highest quintile compared to the remainder 1.44, 95% CI 1.12-1.85), and lower hippocampal volume (OR per decreasing quintile 1.22, 1.11-1.35). These associations were independent of all other covariates, including cognitive function. CONCLUSIONS: Subjective memory deficit (SMD) was associated with neuroimaging characteristics in the temporal and hippocampal regions, suggesting that SMD may, at least in some cases, represent a realistic appraisal of underlying brain function independent of measured cognition. However, further research is required for volumetric measures and SMD to establish whether the association reflects lifelong structure or neurodegenerative changes. ©2008AAN Enterprises, Inc.",aged;article;brain size;cerebrospinal fluid;cognitive defect;community care;controlled study;female;gray matter;hippocampus;human;major clinical study;male;memory disorder;neuroimaging;nuclear magnetic resonance imaging;physical activity;priority journal;social behavior;subiculum;white matter,"Stewart, R.;Dufouil, C.;Godin, O.;Ritchie, K.;Maillard, P.;Delcroix, N.;Crivello, F.;Mazoyer, B.;Tzourio, C.",2008,,,0,
1076,Cerebral white matter lesions and subjective cognitive dysfunction: the Rotterdam Scan Study,,Aged;Alzheimer Disease/*diagnosis/genetics/pathology;Apolipoprotein E4;Apolipoproteins E/*genetics;Cerebral Ventricles/*pathology;Genotype;Humans;*Magnetic Resonance Imaging;*Mental Status Schedule;Middle Aged;Netherlands;Risk Factors,"Stewart, R.",2001,Dec 11,,0,
1077,Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease,"BACKGROUND: Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. METHOD: 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination (FWE) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging (DTI)-based and spherical deconvolution analyses. RESULTS: Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction (TVF) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. CONCLUSION: Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics.",Algorithms;Artifacts;Cohort Studies;Corpus Callosum/ diagnostic imaging;Cost of Illness;Diffusion Magnetic Resonance Imaging/ methods;Diffusion Tensor Imaging;Female;Fingers/physiopathology;Humans;Huntington Disease/cerebrospinal fluid/ diagnostic imaging/physiopathology;Male;Middle Aged;Motor Activity;Organ Size;Reproducibility of Results;Severity of Illness Index;White Matter/ diagnostic imaging;Corpus callosum;Dti;Diffusion MRI;Disease burden;Huntington's disease;Tractography,"Steventon, J. J.;Trueman, R. C.;Rosser, A. E.;Jones, D. K.",2016,May 30,,0,
1078,Robust MR-based approaches to quantifying white matter structure and structure/function alterations in Huntington's disease,"Background: Huge advances have been made in understanding and addressing confounds in diffusion MRI data to quantify white matter microstructure. However, there has been a lag in applying these advances in clinical research. Some confounds are more pronounced in HD which impedes data quality and interpretability of patient-control differences. This study presents an optimised analysis pipeline and addresses specific confounds in a HD patient cohort. Method: 15 HD gene-positive and 13 matched control participants were scanned on a 3T MRI system with two diffusion MRI sequences. An optimised post processing pipeline included motion, eddy current and EPI correction, rotation of the B matrix, free water elimination (FWE) and tractography analysis using an algorithm capable of reconstructing crossing fibres. The corpus callosum was examined using both a region-of-interest and a deterministic tractography approach, using both conventional diffusion tensor imaging (DTI)-based and spherical deconvolution analyses. Results: Correcting for CSF contamination significantly altered microstructural metrics and the detection of group differences. Reconstructing the corpus callosum using spherical deconvolution produced a more complete reconstruction with greater sensitivity to group differences, compared to DTI-based tractography. Tissue volume fraction (TVF) was reduced in HD participants and was more sensitive to disease burden compared to DTI metrics. Conclusion: Addressing confounds in diffusion MR data results in more valid, anatomically faithful white matter tract reconstructions with reduced within-group variance. TVF is recommended as a complementary metric, providing insight into the relationship with clinical symptoms in HD not fully captured by conventional DTI metrics.",,"Steventon, J. J.;Trueman, R. C.;Rosser, A. E.;Jones, D. K.",2015,,,0,1077
1079,Small vessel disease and the resting functional architecture of the brain,"Small vessel disease (SVD) is linked to cognitive impairment and dementia, yet little is known regarding functional activation in patients with SVD. Resting fMRI recordings suggest reduced connectivity in prefrontal, parietal and cingulate nodes and reciprocally increased connectivity in cerebellum, alterations which predicted neuropsychological test performance. Together with diffusion tensor tensor imaging studies, these data support of a model of disrupted connectivity as a systems-level approach to the cognitive disturbances seen in SVD.",Brain/ blood supply/pathology/ physiopathology;Cerebrovascular Disorders/pathology/ physiopathology;Cognition Disorders/pathology/ physiopathology;Humans;Magnetic Resonance Imaging;Neural Pathways/pathology/ physiopathology,"Stevens, R. D.;Hannawi, Y.;Sair, H.",2014,Jul,10.1038/jcbfm.2014.69,0,
1080,Pravastatin improves cerebral vasomotor reactivity in patients with subcortical small-vessel disease,"BACKGROUND AND PURPOSE: Recent investigations have suggested an important role of statins in the prevention of stroke and dementia independent of their lipid-lowering properties. Using transcranial Doppler sonography (TCD), we examined acetazolamide reactivity as a marker of cerebral vasoreactivity in patients with subcortical small-vessel disease before and after pravastatin treatment. METHODS: In 16 patients (mean age 68+/-10 years) with subcortical small-vessel disease, cerebral vasomotor reactivity was tested using TCD insonating the middle cerebral artery. Cerebral blood flow velocity (CBFV) increase after bolus injection of 1 g acetazolamide was determined before and after 2-month treatment with pravastatin sodium 20 mg daily. RESULTS: Relative CBFV increase was significantly greater after pravastatin treatment (41.9+/-23.7% versus 55.7+/-18.3%, P=0.004). Comparison of CBFV at rest before and after treatment with pravastatin did not show significant differences. There was a strong negative correlation between the pravastatin-induced enhancement of vasomotor reactivity and the pretreatment CBFV increase (beta=-0.64, P=0.019). No associations were found between the effect of pravastatin on vasomotor reactivity and pretreatment levels or changes of LDL cholesterol. CONCLUSIONS: This pilot study provides the first evidence for a significant improvement of cerebral vasomotor reactivity by statin therapy in patients with cerebral small-vessel disease. The results may help to elucidate the preventive effect of statins and provide insights into the pathophysiology of cerebral small-vessel disease.","Acetazolamide;Aged;Blood Flow Velocity/drug effects;Cholesterol, LDL/blood/drug effects;Cognition Disorders/diagnosis/etiology;Dementia, Vascular/*drug therapy/physiopathology;Epilepsy/diagnosis/etiology;Female;Gait Disorders, Neurologic/diagnosis/etiology;Humans;Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use;Ischemic Attack, Transient/diagnosis/etiology;Linear Models;Magnetic Resonance Imaging;Male;Pilot Projects;Pravastatin/*therapeutic use;Prospective Studies;Subtraction Technique;Treatment Outcome;Ultrasonography, Doppler, Transcranial;Vasomotor System/*drug effects/physiopathology","Sterzer, P.;Meintzschel, F.;Rosler, A.;Lanfermann, H.;Steinmetz, H.;Sitzer, M.",2001,Dec 1,,0,
1081,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with severe factor XII deficiency,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited adult-onset microangiopathy caused by missense mutations in the Notch3gene on chromosome 19. However, common vascular risk factors may additionally modify clinical expression and progression of the disease. The role of various prothrombotic factors has also been implied. We report a case of a middle-aged man with typical clinical, neuroimaging and histological features of CADASIL, but with notably prolonged activated partial thromboplastin time. Hematological investigations revealed severe clotting Factor XII deficiency. This case illustrates that the occurrence of vascular risk factors should not be overlooked in patients with CADASIL.",adult;article;blood clotting factor 12 deficiency;brain angiography;CADASIL;case report;dysarthria;dysphagia;echography;electrocardiogram;family history;histopathology;human;human tissue;laboratory test;male;neuroimaging;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;partial thromboplastin time;skin biopsy;transesophageal echocardiography;transthoracic echocardiography,"Sternic, N.;Pavlovic, A.;Miljic, P.;Bajcetic, M.;Lackovic, M.;Lackovic, V.",2009,,,0,
1082,White matter changes on diffusion tensor imaging in the finnish geriatric intervention study to prevent cognitive impairment and disability (finger),"Background: FINGER is a multicenter randomized controlled trial (NCT01041989) that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of diffusion tensor imaging. Methods: FINGER targeted 1260 at-risk elderly from the general Finnish population, aged 60-77 years and without dementia/substantial cognitive impairment. Primary outcome was change in cognition (Neuropsychological Test battery, z-score). 60 cases (26 control, 34 intervention) who underwent baseline and 2-year followup MRI exams were selected from FINGER. Fractional anisotropy (FA) change and its correlation with cognitive change were analyzed using Tract-Based Spatial Statistics (TBSS). Results: The total composite z-score and scores of memory, processing speed, and executive function domains showed significantly improved in the intervention group (p<0.047), but no significant change in the control group (p>0.061). Significant FA reduction was found in both groups (corrected for multiple comparisons, p<0.05). In the control group the FA reduction localized at genu of corpus callosum (CC). In the intervention group, the FA reduction localized at CC, bilateral posterior cingulum, frontal and cerebellar white matter (WM), left corticospinal track, fornix, and occipital and parietal WM, external capsule, superior and inferior longitudinal fasciculuses, right postcentral gyral WM. In the control group the FA reduction positively correlated with decrease of the total composite z-score at CC genu and right frontal, and also positively correlated with memory and executive function at CC body and genu, bilateral frontal, right external capsule, corticospinal track, cingulum, parietal WM, and superior longitudinal fasciculus (corrected, p<0.05) However, no any correlation was found in the intervention group. Conclusions: The 2-year multimodal intervention can change the evolution of WM. Considering the fact that FA change correlated with change in cognition in the control group but not in the intervention group, the reduction of FA in the two groups might involve different mechanisms.",adult;cardiovascular risk;cingulum (brain);cognitive defect;control group;controlled clinical trial;controlled study;corpus callosum;diet;diffusion tensor imaging;executive function;exercise;exploratory research;external capsule;finger;Finn (citizen);follow up;fractional anisotropy;human;intervention study;major clinical study;memory;middle aged;monitoring;neuropsychological test;prevention;randomized controlled trial;statistics;superior longitudinal fasciculus;velocity;white matter,"Stephen, R.;Solomon, A.;Ngandu, T.;Levalahti, E.;Rinne, J. O.;Kemppainen, N.;Parkkola, R.;Antikainen, R.;Strandberg, T.;Kivipelto, M.;Soininen, H.;Liu, Y.",2017,,,0,
1083,"Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition","BACKGROUND: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. OBJECTIVES: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. METHODS: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. RESULTS: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta-coefficient -0.29, p = 0.001) and hippocampal volume (beta-coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p < 0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15, 95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. CONCLUSIONS: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.",Aging;cognition;dementia;neuroimaging,"Stephen, R.;Liu, Y.;Ngandu, T.;Rinne, J. O.;Kemppainen, N.;Parkkola, R.;Laatikainen, T.;Paajanen, T.;Hanninen, T.;Strandberg, T.;Antikainen, R.;Tuomilehto, J.;Keinanen Kiukaanniemi, S.;Vanninen, R.;Helisalmi, S.;Levalahti, E.;Kivipelto, M.;Soininen, H.;Solomon, A.",2017,,,0,
1084,Alzheimer and vascular neuropathological changes associated with different cognitive states in a non-demented sample,"The state between aging with no cognitive impairment and dementia has become a major focus for intervention. The neuropathological and neurobiological correlates of this intermediate state are therefore of considerable interest, particularly from population representative samples. Here we investigate the neuropathological profile associated with different cognitive ability levels measured using strata defined by Mini Mental State Examination (MMSE) scores. One hundred and fifty one individuals were stratified into three cognitive groups including: non-, mildly, and moderately impaired at death. Alzheimer's disease, atrophy, and vascular pathologies were investigated. Mild impairment was associated with an increased risk of vascular pathologies including small vessel disease and lacunes. In contrast, the moderately impaired group showed a more extensive pattern of pathology, including tangles and neuritic plaques (entorhinal/hippocampus), atrophy (cortical and hippocampal), and vascular disease (small vessel disease, lacunes, and infarcts). In a population-based sample of older people, MMSE score defined strata are associated with multiple pathologies. The profile of AD and vascular changes becomes more complex with increased cognitive impairment and these changes are likely to constitute a major substrate for age associated cognitive impairment. The results highlight the need for rigorous investigation of both neurodegenerative and vascular risks factors in old age. © 2012-IOS Press and the authors. All rights reserved.",apolipoprotein E;aged;aging;Alzheimer disease;angina pectoris;article;autopsy;cerebrovascular disease;cognitive defect;comorbidity;dementia;diabetes mellitus;disease association;disease severity;female;genotype;health status;heart infarction;human;hypertension;immunohistochemistry;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;neuropathology;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;risk factor;cerebrovascular accident,"Stephan, B. C. M.;Matthews, F. E.;Ma, B.;Muniz, G.;Hunter, S.;Davis, D.;McKeith, I. G.;Foster, G.;Ince, P. G.;Brayne, C.",2012,,,0,
1085,"Associations between white matter lesions, cerebrovascular risk factors, and low CSF Aβ42","OBJECTIVE: To analyze a putative relationship between white matter lesions (WMLs), risk factors for WMLs, and Alzheimer disease (AD) as measured with the surrogate marker CSF Aβ42. METHODS: The authors analyzed effects of acquired risk factors for cerebrovascular disease and WMLs on AD as measured with an intermediate marker, CSF Aβ42. A total of 127 consecutive patients with subjective memory impairment (mean age 66 years; 57 women) investigated at a university-based memory clinic had brain MRI scans. WMLs were rated on a 12-point scale with a semiquantitative procedure. They used path analysis with established and possible risk factors for WMLs and for reduced CSF Aβ42 (age, hypertension, hyperhomocysteinemia, hypercholesterolemia, APOE-&epsiv;4) as variables. RESULTS: The WML score was 1.5 points higher (p < 0.05) in hypertensive than in nonhypertensive patients and 1.9 points higher (p < 0.05) in patients with hyperhomocysteinemia than in those with normal homocysteine levels. Hypercholesterolemia increased the probability of low CSF Aβ42 levels by 0.2 (p < 0.05). For each point increase in WML score, the probability of low CSF Aβ42 levels increased by 0.03 (p < 0.05). APOE-&epsiv;4 was associated with reduced CSF Aβ42 (p < 0.01). CONCLUSION: Both hypercholesterolemia and white matter lesions may contribute to low CSF Aβ42 by independent mechanisms. Copyright © 2006 by AAN Enterprises, Inc.",amyloid beta protein[1-42];apolipoprotein E4;homocysteine;adult;aged;Alzheimer disease;amino acid brain level;article;brain damage;cerebrospinal fluid;cerebrovascular disease;clinical feature;controlled study;disease association;disease marker;female;human;hypercholesterolemia;hyperhomocysteinemia;hypertension;major clinical study;male;memory disorder;Mini Mental State Examination;nuclear magnetic resonance imaging;priority journal;risk assessment;scoring system;white matter,"Stenset, V.;Johnsen, L.;Kocot, D.;Negaard, A.;Skinningsrud, A.;Gulbrandsen, P.;Wallin, A.;Fladby, T.",2006,,,0,
1086,"Associations between white matter lesions, cerebrovascular risk factors, and low CSF Abeta42","OBJECTIVE: To analyze a putative relationship between white matter lesions (WMLs), risk factors for WMLs, and Alzheimer disease (AD) as measured with the surrogate marker CSF Abeta42. METHODS: The authors analyzed effects of acquired risk factors for cerebrovascular disease and WMLs on AD as measured with an intermediate marker, CSF Abeta42. A total of 127 consecutive patients with subjective memory impairment (mean age 66 years; 57 women) investigated at a university-based memory clinic had brain MRI scans. WMLs were rated on a 12-point scale with a semiquantitative procedure. They used path analysis with established and possible risk factors for WMLs and for reduced CSF Abeta42 (age, hypertension, hyperhomocysteinemia, hypercholesterolemia, APOE-epsilon4) as variables. RESULTS: The WML score was 1.5 points higher (p < 0.05) in hypertensive than in nonhypertensive patients and 1.9 points higher (p < 0.05) in patients with hyperhomocysteinemia than in those with normal homocysteine levels. Hypercholesterolemia increased the probability of low CSF Abeta42 levels by 0.2 (p < 0.05). For each point increase in WML score, the probability of low CSF Abeta42 levels increased by 0.03 (p < 0.05). APOE-epsilon4 was associated with reduced CSF Abeta42 (p < 0.01). CONCLUSION: Both hypercholesterolemia and white matter lesions may contribute to low CSF Abeta42 by independent mechanisms.","Adult;Aged;Alzheimer Disease/*cerebrospinal fluid/complications/*pathology;Amyloid beta-Peptides/*cerebrospinal fluid;Brain/*pathology;Brain Injuries/*cerebrospinal fluid;Cerebrovascular Disorders/*cerebrospinal fluid;Female;Humans;Magnetic Resonance Imaging/methods;Male;Memory Disorders/cerebrospinal fluid/etiology/pathology/physiopathology;Middle Aged;Models, Biological;Risk Factors;Severity of Illness Index","Stenset, V.;Johnsen, L.;Kocot, D.;Negaard, A.;Skinningsrud, A.;Gulbrandsen, P.;Wallin, A.;Fladby, T.",2006,Sep 12,10.1212/01.wnl.0000234030.77831.5a,0,
1087,White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels,"OBJECTIVE: To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. MATERIAL AND METHODS: 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. RESULTS: WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. CONCLUSIONS: WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/pathology/physiopathology;Amyloid beta-Peptides/analysis/*cerebrospinal fluid;Apolipoprotein E4/genetics;Biomarkers/analysis/cerebrospinal fluid;Brain/metabolism/*pathology/physiopathology;Cognition Disorders/cerebrospinal fluid/*pathology/physiopathology;Disease Progression;Female;Humans;Hypercholesterolemia/complications;Hyperhomocysteinemia/complications;Magnetic Resonance Imaging;Male;Memory Disorders/cerebrospinal fluid/*pathology/physiopathology;Middle Aged;Nerve Fibers, Unmyelinated/metabolism/*pathology;Neuropsychological Tests;Peptide Fragments/analysis/*cerebrospinal fluid;Plaque, Amyloid/metabolism/pathology;Predictive Value of Tests;Prognosis;Statistics as Topic","Stenset, V.;Hofoss, D.;Johnsen, L.;Skinningsrud, A.;Berstad, A. E.;Negaard, A.;Reinvang, I.;Gjerstad, L.;Fladby, T.",2008,Dec,10.1111/j.1600-0404.2008.01045.x,0,
1088,White Matter Lesion Load Increases the Risk of Low CSF Aβ42 in Apolipoprotein E-e{open}4 Carriers Attending a Memory Clinic,"White matter lesions (WMLs) are age-related manifestations of ischemic cerebrovascular disease and increase the risk for Alzheimer's disease (AD). The apolipoprotein E (ApoE) e{open}4 allele is a risk factor for late onset AD and has been related to low cerebrospinal fluid (CSF) Aβ42 levels and to cerebrovascular disease. The present study analyzed the relationship between WMLs, ApoE-e{open}4 genotype, and low CSF Aβ42. METHODS: A total of 235 memory clinic attenders were stratified in 3 groups according to WML load. WMLs were rated on axial T2 magnetic resonance imaging images. Group 1 had no or only small amounts of periventricular (PV) or subcortical (SC) WMLs, WML group 2 had high amounts of PV WMLs and low amounts of SC WMLs, and WML group 3 had high amounts of both PV and SC WMLs. In each WML group, ApoE-e{open}4 genotype was used in logistic regression as a predictor for low CSF Aβ42 (cutoff ≤450 ng/L). Results: The odds ratio (OR) of having low CSF Aβ42 was significantly increased in the presence of ApoE-e{open}4 only in WML group 3 (OR 3.69, P=.009). CONCLUSION: A high WML load may interact with the ApoE-e{open}4 genotype and increase the risk for reduced CSF Aβ42 in patients attending a memory clinic. © 2009 by the American Society of Neuroimaging.",amyloid beta protein[1-42];apolipoprotein E;apolipoprotein E epsilon 4;unclassified drug;adult;aged;amnesia;article;brain damage;cerebrospinal fluid;cognitive defect;controlled study;female;genotype;heterozygote;human;major clinical study;male;nuclear magnetic resonance imaging;periventricular white matter lesion;risk assessment;subcortical white matter lesion,"Stenset, V.;Hofoss, D.;Johnsen, L.;Berstad, A. E.;Negaard, A.;Skinningsrud, A.;Gjerstad, L.;Fladby, T.",2011,,,0,
1089,White matter lesion load increases the risk of low CSF Abeta42 in apolipoprotein E-varepsilon4 carriers attending a memory clinic,"BACKGROUND: White matter lesions (WMLs) are age-related manifestations of ischemic cerebrovascular disease and increase the risk for Alzheimer's disease (AD). The apolipoprotein E (ApoE) varepsilon4 allele is a risk factor for late onset AD and has been related to low cerebrospinal fluid (CSF) Abeta42 levels and to cerebrovascular disease. The present study analyzed the relationship between WMLs, ApoE-varepsilon4 genotype, and low CSF Abeta42. METHODS: A total of 235 memory clinic attenders were stratified in 3 groups according to WML load. WMLs were rated on axial T2 magnetic resonance imaging images. Group 1 had no or only small amounts of periventricular (PV) or subcortical (SC) WMLs, WML group 2 had high amounts of PV WMLs and low amounts of SC WMLs, and WML group 3 had high amounts of both PV and SC WMLs. In each WML group, ApoE-varepsilon4 genotype was used in logistic regression as a predictor for low CSF Abeta42 (cutoff</=450 ng/L). RESULTS: The odds ratio (OR) of having low CSF Abeta42 was significantly increased in the presence of ApoE-varepsilon4 only in WML group 3 (OR 3.69, P=.009). CONCLUSION: A high WML load may interact with the ApoE-varepsilon4 genotype and increase the risk for reduced CSF Abeta42 in patients attending a memory clinic.",Aged;Alleles;Amyloid beta-Peptides/ cerebrospinal fluid/ genetics;Analysis of Variance;Apolipoprotein E4/ genetics;Female;Genotype;Humans;Leukoencephalopathies/ cerebrospinal fluid/ genetics;Logistic Models;Magnetic Resonance Imaging;Male;Memory Disorders/ cerebrospinal fluid/ genetics;Risk Factors,"Stenset, V.;Hofoss, D.;Johnsen, L.;Berstad, A. E.;Negaard, A.;Skinningsrud, A.;Gjerstad, L.;Fladby, T.",2011,Apr,10.1111/j.1552-6569.2009.00444.x,0,
1090,White matter lesion subtypes and cognitive deficits in patients with memory impairment,"Aim: To analyze the relationship between periventricular (PV) and subcortical (SC) white matter lesions (WML) and cognitive function in patients with memory impairment. Methods: In total, 253 patients with Global Deterioration Scale scores ≥3 who had been referred to a university-based memory unit due to memory complaints were included (mean age 69.7 years, 124 females). Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat), and full test results were available for 217 patients. PV and SC WML loads (semi-quantitative rating on axial T2-weighted MRI scans) were used in linear regression as predictors of cognition. Results: MMSE was significantly correlated with SC WML (p = 0.005), but not with PV WML (p = 0.19). Cognistat tests for orientation, comprehension, visuoconstruction, calculation, similarities, and judgment were negatively correlated with SC WML (p < 0.01), as was verbal memory with parieto-occipital SC WML (p < 0.05). Visuoconstruction and calculation were negatively correlated with PV WML (p < 0.05). Parieto-occipital WML were more strongly related to cognition than fronto-temporal WML. Only SC WML were significantly correlated with cognition when PV and SC WML were entered simultaneously in the regression model. Conclusion: In patients with cognitive impairment, SC WML, in particular in parieto-occipital regions, were associated with reduced cognitive function. Copyright © 2008 S. Karger AG.",adult;aged;article;brain damage;cognition;cognitive defect;female;Global Deterioration scale;human;major clinical study;male;memory disorder;Mini Mental State Examination;Neurobehavioral Cognitive Status Examination;priority journal;rating scale;white matter,"Stenset, V.;Hofoss, D.;Berstad, A. E.;Negaard, A.;Gjerstad, L.;Fladby, T.",2008,,,0,
1091,Cingulum fiber diffusivity and CSF T-tau in patients with subjective and mild cognitive impairment,"Diffusion tensor imaging (DTI) and CSF biomarkers are useful diagnostic tools to differentiate patients with mild cognitive impairment (MCI) from normal controls, and may help predict conversion to dementia. Total Tau protein (T-tau) and DTI parameters are both markers for axonal damage, thus it is of interest to determine if DTI parameters are associated with elevated CSF T-tau levels in patients with cognitive impairment. For this purpose, patients with subjective cognitive impairment (SCI) and MCI were recruited from a university based memory clinic. Regions of interest were used to determine fractional anisotropy (FA), radial diffusivity (DR) and axial diffusivity (DA) in known white matter tracts in patients with MCI (n=39) and SCI (n=8) and 26 cognitively healthy controls. Significant lower FA and higher DR values were observed in patients with pathological vs. patients with normal CSF T-tau levels and vs. controls in left posterior cingulum fibers. T-tau values were negatively correlated with FA and positively correlated with DR values in the posterior cingulum fibers. Cingulum fiber diffusivity was related to T-tau pathology in SCI/MCI patients and altered DR may suggest that loss of myelin contributes to early white matter changes in patients at risk of developing Alzheimer's disease (AD).","Adult;Aged;Anisotropy;Brain Mapping;Cognition Disorders/ cerebrospinal fluid/ pathology;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Image Processing, Computer-Assisted;Linear Models;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;tau Proteins/ cerebrospinal fluid","Stenset, V.;Bjornerud, A.;Fjell, A. M.;Walhovd, K. B.;Hofoss, D.;Due-Tonnessen, P.;Gjerstad, L.;Fladby, T.",2011,Apr,10.1016/j.neurobiolaging.2009.04.014,0,
1092,Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia,"This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses.",Alzheimer's disease;Arterial spin labeling;Behavioral variant frontotemporal dementia;Diffusion tensor imaging;Structural MRI,"Steketee, R. M.;Meijboom, R.;de Groot, M.;Bron, E. E.;Niessen, W. J.;van der Lugt, A.;van Swieten, J. C.;Smits, M.",2016,Jul,10.1016/j.neurobiolaging.2016.03.031,0,
1093,Kidney function and white matter disease in young stroke patients: Analysis of the stroke in young fabry patients study population,"BACKGROUND AND PURPOSE-: Impaired kidney function is thought to be associated with small vessel disease, outcome, and mortality in the general stroke population. Data are limited regarding young patients. The aim of this study was to investigate the association of kidney function and white matter hyperintensities (WMHs) in young patients with first ischemic stroke. METHODS-: We analyzed 2500 young (18-55 years) patients with first-ever ischemic stroke from the prospective observational Stroke in Young Fabry Patients (SIFAP1) study with available MRI data on WMH. Of these, 2009 had available data concerning estimated glomerular filtration rate (eGFR). Kidney function was expressed as eGFR by the Modification of Diet in Renal Disease method. Deep WMHs on MRI were classified by the Fazekas score. Multivariate analysis was performed using a regression model with random effects. RESULTS-: Mean eGFR was 96.7 mL/min in those with WMH Grade 0 to 1 (none to mild), 90.7 mL/min in WMH Grade 2 (moderate), and 89 mL/min in WMH Grade 3 (severe). Univariate analysis revealed WMH to be associated with age (P<0.001), hypertension (P<0.001), cardiovascular disease (P=0.015), overweight (body mass index >25 kg/m; P=0.013), current smoking (P=0.044), and eGFR (P=0.009). In multivariate analysis, age, hypertension, and eGFR remained associated with WMH severity. CONCLUSIONS-: In young patients with acute ischemic stroke, lower eGFR values in the normal range are associated with the presence of moderate to severe WMH. CLINICAL TRIAL REGISTRATION-: URL: http://clinicaltrials.gov. Unique Identifier: NCT00414583. © 2012 American Heart Association, Inc.",NCT00414583;adult;age distribution;article;body mass;brain ischemia;cardiovascular disease;central nervous system disease;clinical assessment tool;cross-sectional study;disease association;disease severity;estimated glomerular filtration rate;female;glomerulus filtration rate;human;hypertension;image analysis;kidney function;major clinical study;male;Modification of Diet in Renal Disease;nervous system parameters;nuclear magnetic resonance imaging;obesity;observational study;priority journal;prospective study;smoking;white matter hyperintensity;white matter injury,"Steinicke, R.;Gaertner, B.;Grittner, U.;Schmidt, W.;Dichgans, M.;Heuschmann, P. U.;Tanislav, C.;Putaala, J.;Kaps, M.;Endres, M.;Schmidt, R.;Fazekas, F.;Norrving, B.;Rolfs, A.;Martus, P.;Tatlisumak, T.;Enzinger, C.;Jungehulsing, G. J.",2012,,,0,
1094,The significance of white matter lucencies on CT scan in relation to cognitive impairment,"As part of a prospective clinicopathological study a cohort of ""normal"" elderly volunteers (n = 110) has been investigated with CT scans, psychometric testing (Extended Scale for Dementia) and neurological examination. CT scans were evaluated by a neuroradiologist for the presence or absence of white matter lucencies (WML). WML were defined as patchy or diffuse areas of decreased attenuation involving only white matter and with no change in adjacent ventricles or sulci. The 12 subjects with WML had lower scores on the ESD than the 98 subjects without WML (mean ESD with WML 229.5 +/- 14; without WML 236.7 +/- 8.6, t-test p less than .01) and the difference remains significant even after adjusting for the possible confounding effects of age (ANCOVA, P less than .043).","Aged;Aged, 80 and over;Brain/*radiography;Cognition Disorders/*psychology;Humans;*Tomography, X-Ray Computed","Steingart, A.;Lau, K.;Fox, A.;Diaz, F.;Fisman, M.;Hachinski, V.;Merskey, H.",1986,Nov,,0,
1095,Cognitive and neurologic findings in demented patients with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis),"A series of patients referred to the University of Western Ontario, London, Dementia Study for investigation of possible dementia underwent computed tomographic scans, psychometric testing (Extended Scale for Dementia [ESD]), and neurologic examination. Thirty-nine of the 113 patients studied (ischemic score, less than or equal to 4) were found to have leuko-araiosis, which we have defined as patchy or diffuse lucencies in the white matter. Patients with leuko-araiosis had significantly lower mean scores on the ESD, 109.7 +/- 61.2, compared with mean scores of 148.5 +/- 78.0 in those without. However, only a trend toward lower scores on the ESD was observed when age, sex, education, and infarct were taken into account in the analysis of covariance. Leuko-araiosis was found to be associated with increasing age, hypertension, abnormalities of power in the limbs, and extensor-plantar responses in this sample of patients. In patients with Alzheimer's disease (AD) alone, diagnosed clinically, 29 out of 91 demonstrated leuko-araiosis on computed tomography, but scores on the ESD in this group overall were not significantly different when those with and without leuko-araiosis were compared. In less advanced cases, however, a highly significant trend was evident for leuko-araiosis to be associated with increased dementia in AD. The results are consistent with the hypothesis that leuko-araiosis is associated with dementia in AD, and that this is either most marked or most easily identifiable before the dementia becomes very severe.","Aged;Aging/pathology;Alzheimer Disease/pathology;Brain/pathology/*radiography;Cognition Disorders/*pathology;Dementia/*pathology;Female;Humans;Male;Myelin Sheath/*pathology;Tomography, X-Ray Computed","Steingart, A.;Hachinski, V. C.;Lau, C.;Fox, A. J.;Fox, H.;Lee, D.;Inzitari, D.;Merskey, H.",1987,Jan,,0,
1096,Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis),"As part of a prospective clinicopathologic study, a cohort of 105 ""normal"" elderly volunteers was investigated with computed tomographic scans, psychometric testing (Extended Scale for Dementia [ESD]) and neurologic examination. Computed tomographic scans were evaluated for the presence or absence of white matter lucencies, termed leuko-araiosis. These are defined as patchy or diffuse areas of decreased attenuation involving only white matter and with no change in adjacent ventricles or sulci. The nine controls with leuko-araiosis had lower scores on the ESD than the 96 controls without leuko-araiosis (mean ESD with leuko-araiosis, 227.1 +/- 14; without leuko-araiosis, 237.1 +/- 8), and the difference remains significant even after adjusting for the possible confounding effects of age, sex, education, and infarct detected on computed tomography. Significant differences were also found comparing subjects with leuko-araiosis and those without in respect to abnormal gait, limb power, plantar response, and the rooting and palmomental reflexes. Leuko-araiosis may represent a marker for early dementia. The pathophysiology of this finding remains uncertain. Our results suggest that white matter abnormalities play a role in the development of intellectual impairment in the elderly.","Aged;Aged, 80 and over;Brain/pathology/*radiography;Cerebrovascular Disorders/diagnosis;Cognition Disorders/*diagnosis;Dementia/*diagnosis;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Myelin Sheath/*pathology/physiopathology;*Tomography, X-Ray Computed","Steingart, A.;Hachinski, V. C.;Lau, C.;Fox, A. J.;Diaz, F.;Cape, R.;Lee, D.;Inzitari, D.;Merskey, H.",1987,Jan,,0,
1097,Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration,"BACKGROUND AND PURPOSE: Biomarkers as indicators for the progression of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain still elusive. We performed a cross-sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV-infected patients. METHODS: We enrolled 94 patients (82 men and 12 women; mean age 45 +/- 10 years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho-tau, beta-amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF. RESULTS: We found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV-infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho-tau or A-beta-amyloid in CSF analysis. CONCLUSIONS: Our results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho-tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.",AIDS Dementia Complex/ cerebrospinal fluid/ pathology;Biomarkers/cerebrospinal fluid;Brain/ pathology;Cognition Disorders/cerebrospinal fluid/pathology;Cross-Sectional Studies;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/cerebrospinal fluid/pathology;Neuropsychological Tests;tau Proteins/ cerebrospinal fluid,"Steinbrink, F.;Evers, S.;Buerke, B.;Young, P.;Arendt, G.;Koutsilieri, E.;Reichelt, D.;Lohmann, H.;Husstedt, I. W.",2013,Mar,10.1111/ene.12006,0,
1098,Delayed resolution of white matter changes following therapy of B burgdorferi encephalitis,,antigen;ceftriaxone;immunoglobulin G antibody;prednisolone;tuberculostatic agent;aged;article;ataxia;Babinski reflex;bladder dysfunction;Borrelia burgdorferi;Borrelia infection;case report;cerebrospinal fluid analysis;clinical feature;dementia;diagnostic imaging;disease course;encephalitis;encephalomyelitis;female;follow up;gait disorder;human;image analysis;nuclear magnetic resonance imaging;priority journal;symptom;tendon reflex;tick bite;white matter,"Steinbach, J. P.;Melms, A.;Skalej, M.;Dichgans, J.",2005,,,0,
1099,Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects,"BACKGROUND: Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) epsilon 4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer's disease, vascular dementia, and depression. METHODS: The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. RESULTS: Older age, lower Mini-Mental State Examination score, and having any APOE epsilon 4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE epsilon 4 allele, and white matter lesion volume among depressed patients. CONCLUSIONS: These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.",Aged;Alleles;Apolipoproteins E/ genetics;Case-Control Studies;Cerebrovascular Disorders/complications/ genetics;Cohort Studies;Cross-Sectional Studies;Depression/complications/ genetics;Female;Genotype;Geriatric Assessment/statistics & numerical data;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Reproducibility of Results;Severity of Illness Index,"Steffens, D. C.;Trost, W. T.;Payne, M. E.;Hybels, C. F.;MacFall, J. R.",2003,Oct 1,,0,
1100,"Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study","OBJECTIVE: Several studies suggest that depression is a risk factor for development of dementia in the elderly. In a study of older depressed individuals, the authors examined both neuroimaging and genetic factors in development of dementia. The authors hypothesized that change in subcortical gray matter and white matter hyperintensity volumes would be associated with development of dementia, as would presence of an apolipoprotein E (APOE) epsilon 4 allele. METHODS: The sample consisted of 161 older depressed subjects without dementia who had magnetic resonance imaging scans at baseline and at two years. Blood samples were also taken to determine APOE genotype. All participants were treated with antidepressants using a guideline-based treatment algorithm. Their cognitive status was evaluated annually. A consensus panel of experts evaluated each case to determine cognitive status and assign a diagnosis. RESULTS: Twenty subjects became demented over the follow-up period (5.4 years on average). Change in white matter hyperintensity volume was significantly associated with development of dementia, especially among non-Alzheimer dementias. There was a trend for change in subcortical gray matter hyperintensity volume to be associated with incident dementia. APOE genotype was not associated with onset of dementia. CONCLUSION: Worsening cerebrovascular disease in older depressed adults is associated with cognitive decline and dementia, particularly of the non-Alzheimer disease type. The association of change in white matter lesion volume and incident dementia among depressed elders extends the vascular depression hypothesis of geriatric depression to include cognitive outcomes of depression in the elderly.","Age Factors;Aged;Apolipoprotein E4/ genetics;Brain/ pathology;Cerebrovascular Disorders/pathology;Cognition Disorders/diagnosis/epidemiology/ pathology;Consensus;Dementia/diagnosis/epidemiology/ pathology;Dementia, Vascular/diagnosis/epidemiology/pathology;Depressive Disorder, Major/diagnosis/epidemiology/ pathology;Disease Progression;Female;Follow-Up Studies;Genotype;Geriatric Assessment;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging/ statistics & numerical data;Male;Neuropsychological Tests;Prevalence","Steffens, D. C.;Potter, G. G.;McQuoid, D. R.;MacFall, J. R.;Payne, M. E.;Burke, J. R.;Plassman, B. L.;Welsh-Bohmer, K. A.",2007,Oct,10.1097/JGP.0b013e318048a1a0,0,
1101,Biological and social predictors of long-term geriatric depression outcome,"Objective: In this study, we examined 204 older depressed individuals for up to 64 months to determine factors related to depression outcome. We hypothesized that both presence of vascular brain lesions seen on baseline magnetic resonance imaging (MRI) scans and lower baseline social support measures would be related to worse depression outcome. Method: At study entry, all subjects were at least 59 years old, had a diagnosis of major depression, and were free of other major psychiatric illness and primary neurological illness, including dementia and stroke. Depression was diagnosed via structured interview and clinical assessment by a geriatric psychiatrist who completed a Montgomery Asberg Depression Rating Scale (MADRS) to determine severity of depression. Subjects provided self-report data on social support variables and ability to perform basic and instrumental activities of daily living (ADL, IADL). All subjects agreed to have a baseline standardized MRI brain scan. Ratings of severity of hyperintensities were determined for the periventricular white matter, deep white matter, and subcortical gray matter by two readers who decided by consensus. Treatment was provided by geropsychiatrists following clinical guidelines. Using mixed models to analyze the data, we determined the effect of a variety of demographic, social and imaging variables on the trajectory of MADRS score, the outcome variable of interest. Results: MADRS scores decreased steadily over time. In a final HLM model, in which time since entry, a baseline time indicator, age, gender, education and Mini-mental State Examination score were controlled, subjective social support, instrumental ADL impairment, subcortical gray matter severity, and the interactions of time with social network and with subcortical gray matter lesions remained significantly associated with MADRS score. Conclusions: Both social and biological factors at baseline are associated with longitudinal depression severity in geriatric depression. © 2005 International Psychogeriatric Association.",,"Steffens, D. C.;Pieper, C. F.;Bosworth, H. B.;MacFall, J. R.;Provenzale, J. M.;Payne, M. E.;Carroll, B. J.;George, L. K.;Krishnan, K. R. R.",2005,March,,0,
1102,Subcortical white matter lesions and functional impairment in geriatric depression,"Geriatric depression is associated with significant functional impairment. There is also growing evidence linking vascular brain changes to depression in late life. We sought to examine the relationship between cerebrovascular disease and impairment in basic activities of daily living (BADL) and instrumental activities of daily living (IADL) in a group of older depressives. The sample consisted of 224 depressed adults aged 60 years and above enrolled in Duke's Mental Health Clinical Research Center. All subjects had unipolar major depression and were free of other major psychiatric and neurological illness, including dementia. In a structural interview, subjects reported their medical history and ability to perform both BADL and IADL. Geriatric psychiatrists assessed cognition using the Mini Mental State Examination (MMSE) and depression severity using the Montgomery Ashberg Depression Rating Scale (MADRS). Subjects had a standardized magnetic resonance imaging (MRI) brain scan. MRI scans were processed using a semi-automated method to determine volumes of subcortical white matter lesions (WML) and subcortical gray matter lesions (GML). Logistic regression was used to examine effects of WML and GML controlling for demographic and clinical factors. Greater volume of WML, was associated with impairment in both BADL and IADL, while GML was associated with IADL impairment. In logistic models, WML remained significantly associated with IADL after controlling for the effects of age, gender, depression severity, and medical comorbidity. We concluded that white matter lesions are independently associated with functional impairment. Further studies are needed to understand how these lesions affect function, e.g., through effects on cognition or motor skills. © 2002 Wiley-Liss, Inc.",,"Steffens, D. C.;Bosworth, H. B.;Provenzale, J. M.;MacFall, J. R.",2002,2002,,0,
1103,Vascular risk factors in Alzheimer's disease - preliminary report,"BACKGROUND: The vascular risk factors are associated with an increased risk for vascular cognitive decline (VCD), but also with Alzheimer disease (AD). OBJECTIVE: To investigate vascular risk factors in relation to AD and VCD, with a non-invasive neurosonological methods in a clinical settings. RESULTS: A total of 296 patients with AD and 237 patients with VCD were included in the study. Hypertension, hyperlipidemia, diabetes mellitus, stroke, and white matter changes (p<0.001) were significantly more prevalent in VCD, although they were also present in AD patients. No statistically significant differences were obtained between groups regarding coronary disease, atrial fibrillation, average degree of carotid artery stenosis and carotid intima-media thickness (cITM). However, the patients with AD had carotid artery stenosis "">50%"" (p=0.007) and present plaques (p<0.001) more frequently compared to vascular group. The significant associations between robust cognitive measure and vascular factors, diabetes mellitus, carotid stenosis, cITM, and type of plaques were identified only in VCD, but not in AD group. CONCLUSIONS: The vascular risk factors were more prevalent in VCD group, although they were also present in AD. With few treatment options available in AD, it may be important not to neglect the vascular risk factors.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*epidemiology;Carotid Arteries/ultrasonography;Carotid Intima-Media Thickness;Cerebrovascular Disorders/diagnosis/*epidemiology;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Retrospective Studies;Risk Factors;Statistics, Nonparametric;Tomography, X-Ray Computed","Stefanova, E.;Pavlovic, A.;Jovanovic, Z.;Veselinovic, N.;Despotovic, I.;Stojkovic, T.;Sternic, N.;Kostic, V.",2012,Nov 15,10.1016/j.jns.2012.07.065,0,
1104,Cerebral small vessel disease in middle age and genetic predisposition to late-onset Alzheimer's disease,"INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E epsilon4 (APOE epsilon4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD. METHODS: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study. RESULTS: Microbleed prevalence was 14.5%, and mean +/- standard deviation white matter hyperintensity percentage of total brain volume was 0.41 +/- 0.28%. There was no significant association between APOE epsilon4 carrier status or history of parental dementia and white matter hyperintensity volume (P = .713, .912 respectively) or microbleeds (P = .082, .562 respectively) on multiple regression. DISCUSSION: Genetic predisposition to LOAD, through APOE genotype or AD family history, is not associated with CSVD in middle age.",Cerebral microbleed;Cerebral small vessel disease;Dementia;Mri;Middle age;Risk factors;White matter hyperintensity,"Stefaniak, J. D.;Su, L.;Mak, E.;Sheikh-Bahaei, N.;Wells, K.;Ritchie, K.;Waldman, A.;Ritchie, C. W.;O'Brien, J. T.",2018,Feb,,0,
1105,"CSF biomarkers, impairment of cerebral hemodynamics and degree of cognitive decline in Alzheimer's and mixed dementia","The in vivo diagnosis of Alzheimer's disease (AD) may be facilitated by cerebro-spinal fluid (CSF) biomarkers in combination with imaging and clinical assessments. By determining the concentration of beta amyloid fragments, total tau (t-tau) and phospho-tau (p-tau), it is possible to detect the conversion of mild cognitive impairment (MCI) to AD or distinguish AD vs. pseudo-dementia. However, these markers are poorly sensitive to the progressive disease stages. And far from clear is their role in ""mixed"" forms of dementia, as far as hemodynamic deficits complicate the clinical history. We have studied cerebral hemodynamic impairment in AD patients, relative to control subjects. Mean flow velocity (MFV), pulsatility index (PI) and cerebrovascular reactivity (assayed as breath-holding index, BHI) were evaluated by bilateral transcranial Doppler (TCD) monitoring of middle cerebral arteries. MFV and BHI were significantly lower and PI was significantly higher in AD patients with respect to control subjects. The presence of white-matter changes (WMC) in the AD cases did not influence any of the hemodynamic variables. Noticeably, MMSE score was correlated to BHI reduction (P<0.005). Our results, consistent with the recent literature indicate that hemodynamic impairment is a critical marker of cognitive decline and supports once more the hypothesis of a significant pathigenic role of vascular damage in AD. Similar functional alterations might be early hallmarks in a variety of dementia subtypes, including ""mixed"" dementia, whose prevalence is undoubtedly increased. Assessment of hemodynamic reactivity could provide valuable correlations with individual patient's cognitive profile, which in turn would assist in the identification of critical steps in disease progression and the validation of effective therapies.","Aged;Alzheimer Disease/cerebrospinal fluid/ physiopathology/ultrasonography;Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers/blood;Blood Flow Velocity;Brain/blood supply/pathology/physiopathology;Cerebrovascular Circulation;Cognition;Cognition Disorders/cerebrospinal fluid/ physiopathology/ultrasonography;Cohort Studies;Dementia/cerebrospinal fluid/ physiopathology/ultrasonography;Echoencephalography;Female;Humans;Magnetic Resonance Imaging;Male;Middle Cerebral Artery/physiopathology/ultrasonography;Nerve Fibers, Myelinated/pathology;Peptide Fragments/cerebrospinal fluid;Psychiatric Status Rating Scales;Ultrasonography, Doppler, Transcranial;tau Proteins/cerebrospinal fluid","Stefani, A.;Sancesario, G.;Pierantozzi, M.;Leone, G.;Galati, S.;Hainsworth, A. H.;Diomedi, M.",2009,Aug 15,10.1016/j.jns.2009.02.343,0,
1106,Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit,"BACKGROUND AND PURPOSE: Children with hemoglobin SS sickle cell disease are known to suffer cognitive impairment if they have silent infarct, but recent evidence suggests that patients with hemoglobin SS sickle cell disease may be impaired even if they are free of infarction. We test a hypothesis that cognitive impairment in children with hemoglobin SS sickle cell disease is associated with low hematocrit and MR imaging abnormalities. METHODS: A cohort of 49 patients was examined, all of whom had hemoglobin SS sickle cell disease but no history of clinical stroke. The Wechsler scales, which are standardized and age-adjusted, were used to assess cognitive function. Patients also underwent MR imaging examination of the brain, and hematocrit was measured in a subset of 45 patients. MR images were evaluated by at least two readers, and abnormal imaging findings were evaluated by at least three readers. Any lesion was sufficient to be classified as abnormal, with lesions defined to include lacunar infarction, encephalomalacia, or leukoencephalopathy. Hematocrit data were used if obtained within 3 months of psychometric testing and if there were no confounding events in the patients' charts. Wechsler test scores were then evaluated in relation to imaging findings and hematocrit values. RESULTS: Patients with imaging abnormalities had more cognitive impairment than did patients with normal imaging findings in verbal intelligence quotient (P <.02) and verbal comprehension (P <.01). Patients with low hematocrit had cognitive impairment shown by many performance measures, including full-scale intelligence quotient (P <.006), verbal comprehension (P <.006), and freedom from distractibility (P <.02). Multivariate analysis showed that MR imaging and hematocrit were independent predictors of full-scale intelligence quotient. CONCLUSION: Focal brain injury, revealed by MR imaging, is associated with cognitive impairment, but our data suggest that diffuse brain injury may also contribute to impairment. These findings show that impairment is multifactorial and suggest that chronic brain hypoxia is part of the pathophysiology of sickle cell disease.","Adolescent;Anemia, Sickle Cell/ diagnosis;Brain/pathology;Cerebral Infarction/ diagnosis;Child;Child, Preschool;Cognition Disorders/ diagnosis;Dementia, Vascular/diagnosis;Encephalomalacia/diagnosis;Female;Hematocrit;Humans;Intelligence/physiology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Predictive Value of Tests;Wechsler Scales","Steen, R. G.;Miles, M. A.;Helton, K. J.;Strawn, S.;Wang, W.;Xiong, X.;Mulhern, R. K.",2003,Mar,,0,
1107,Gray matter atrophy in patients with ischemic stroke with cognitive impairment,"BACKGROUND AND PURPOSE - Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function. METHODS - Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership. RESULTS - Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance. CONCLUSIONS - These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures. © 2008 American Heart Association, Inc.",adult;aged;article;attention;brain atrophy;brain infarction;brain region;brain size;cerebrovascular accident;cingulate gyrus;cognition;cognitive defect;controlled study;demography;disease severity;female;frontal cortex;gray matter;human;logistic regression analysis;major clinical study;male;memory;morphometrics;neuropsychological test;nuclear magnetic resonance imaging;occipital lobe;orientation;parietal lobe;priority journal;psychomotor development;temporal cortex;thalamus;white matter,"Stebbins, G. T.;Nyenhuis, D. L.;Wang, C.;Cox, J. L.;Freels, S.;Bangen, K.;Detoledo-Morrell, L.;Sripathirathan, K.;Moseley, M.;Turner, D. A.;Gabrieli, J. D. E.;Gorelick, P. B.",2008,,,0,
1108,White matter hyperintensity and cognitive functioning in the racial and ethnic minority cohort of the Framingham heart study,"Background: Previous studies have demonstrated an association between white matter hyperintensities (WMH) and cognitive performance primarily in Caucasian samples, limiting generalizability to other ethnic and racial groups. This study investigated the association of WMH and cognition in an ethnic and racial minority cohort (Omni) of the Framingham Heart Study and compared these results to the Caucasian (Offspring) cohort. Methods: Quantitative brain MRI and neuropsychological evaluations were performed on stroke- and dementia-free participants. Cognitive assessment included verbal memory, visuospatial memory and organization, language, and executive functioning. Linear regression models were conducted to assess the association between WMH and cognitive function. Results: The Omni group presented with demographic factors that significantly differed from those of the Offspring group: they were younger, but had more stroke risk factors such as hypertension. In the Offspring group, WMH volume was significantly associated with poorer performance on tests of executive function and visual organization. No significant associations between WMH and cognitive measures were found in the Omni group, but no differences (significant interaction terms) were seen between the regression coefficients. Conclusions: The Omni cohort had greater variability in factors that may mediate the association of WMH and cognition. More research is needed to investigate how stroke risk factors impact on the occurrence of WMH and its association with cognition in more diverse cohorts. Copyright © 2010 S. Karger AG, Basel.",adult;aged;article;Caucasian;cognition;controlled study;ethnic or racial aspects;female;human;hypertension;language;major clinical study;male;medical assessment;neuropsychology;nuclear magnetic resonance imaging;quantitative analysis;risk factor;cerebrovascular accident;verbal memory;white matter,"Stavitsky, K.;Du, Y.;Seichepine, D.;Laudate, T. M.;Beiser, A.;Seshadri, S.;Decarli, C.;Wolf, P. A.;Au, R.",2010,,,0,
1109,Significance of Haemodynamic and Haemostatic Factors in the Course of Different Manifestations of Cerebral Small Vessel Disease: The SHEF-CSVD Study-Study Rationale and Protocol,"Rationale. This paper describes the rationale and design of the SHEF-CSVD Study, which aims to determine the long-term clinical and radiological course of cerebral small vessel disease (CSVD) and to evaluate haemostatic and haemodynamic prognostic factors of the condition. Design. This single-centre, prospective, non-interventional cohort study will follow 150 consecutive patients with different clinical manifestations of CSVD (lacunar ischaemic stroke, vascular dementia, vascular parkinsonism or spontaneous deep, intracerebral haemorrhage) and 50 age- and sex-matched controls over a period of 24 months. The clinical and radiological course will be evaluated basing on a detailed neurological, neuropsychological and MRI examinations. Haemodynamic (cerebral vasoreactivity, 24 h blood pressure control) and haemostatic factors (markers of endothelial and platelet dysfunction, brachial artery flow-mediated dilatation test) will be determined. Discussion. The scheduled study will specifically address the issue of haemodynamic and haemostatic prognostic factors and their course over time in various clinical manifestations of CSVD. The findings may aid the development of prophylactic strategies and individualised treatment plans, which are critical during the early stages of the disease.",,"Staszewski, J.;Piusinska-Macoch, R.;Skrobowska, E.;Brodacki, B.;Pawlik, R.;Dutkiewicz, T.;Piechota, W.;Raczka, A.;Tomczykiewicz, K.;Stepien, A.",2013,,10.1155/2013/424695,0,
1110,Vascular parkinsonism and vascular dementia are associated with an increased risk of vascular events or death,"INTRODUCTION: The natural course of vascular parkinsonism (VaP) and dementia (VaD) due to cerebral small vessel disease (SVD) is not well known. The aim of this single-center study was to evaluate the long-term risk of vascular events, death and dependency in patients with VaP or VaD and to compare it with patients without cerebrovascular disease but with high atherothrombotic risk. MATERIAL AND METHODS: Seventy-eight consecutive, functionally independent patients with MRI features of SVD and with recently diagnosed VaD (n = 50) and VaP (n = 28) and 55 controls (control group - CG) with high 10-year risk of total cardiovascular disease (SCORE >/= 5%) were prospectively recruited and followed for 24 months. RESULTS: Patients with SVD had lower prevalence of coronary artery disease compared with the CG (20.5% vs. 40%; p = 0.02) but similar prevalence of other atherothrombotic risk factors including mean age (73.7 +/-7.3 vs. 72 +/-5.9 years, p = 0.09). All outcomes were worse in SVD patients than controls. Thirty-one percent of SVD patients (34% of VaD vs. 25% of VaP, p = 0.45) experienced vascular events or died compared to 6% of controls (p < 0.01). After adjustments for potential confounders (age, sex, vascular risk factors), patients with VaP (HR = 7.5; 95% CI: 1.6-33; p < 0.01) and VaD (HR = 8.7; 95% CI: 2.1-35; p < 0.01) had higher risk of vascular events or death and death or dependency (respectively; HR = 3.9; 95% CI: 0.83-18.8; p = 0.07 and HR = 4.7, 95% CI: 1.1-19.7; p = 0.03). CONCLUSIONS: Patients with VaP or VaD due to SVD had significantly higher risk of vascular events, death and dependency compared to controls with high cardiovascular risk and without cerebrovascular disease.",cerebral small vessel disease;mortality;prognosis;vascular dementia;vascular events;vascular parkinsonism,"Staszewski, J.;Piusinska-Macoch, R.;Brodacki, B.;Skrobowska, E.;Macek, K.;Stepien, A.",2017,,,0,
1111,Risk of vascular events in different manifestations of cerebral small vessel disease: A 2-year follow-up study with a control group,"Background and purpose: Natural course of cerebral small vessel disease (CSVD) has not yet been thoroughly studied. The aim of the single center study was to establish risk of vascular events or death in different manifestations of CSVD. Methods: 150 consecutive, functionally independent patients with marked MRI features of CSVD and with recent lacunar stroke (n = 52, LS), deep hemorrhagic stroke (n = 20, HS), vascular parkinsonism (n = 28, VaP), vascular dementia (n = 50, VaD) and 55 controls (CG) with high atherothrombotic risk free of cerebrovascular events were prospectively recruited and followed for 24 months. Results: Mean age and sex distribution were similar in CSVD and CG but patients with CSVD were less likely to have CAD (19% vs 40%, p = 0.02) and tended to have higher prevalence of diabetes (54% vs 37%, p = 0.11). The risk of vascular events or death was increased in any patients with moderate to severe white matter lesions at baseline MRI (HR 2.0; 95% CI 0.85-7.2), in CSVD (4.56; 95% CI 1.3-14.9) vs CG, regardless of its clinical manifestation: LS or HS (HR 4.70; 95% CI 1.3-16.2) and VaD or VaP (HR 4.59; 95% CI 1.3-15.7). Adjustment for confounders did not change the results substantially. Conclusions: Patients with symptomatic CSVD regardless of the clinical (acute or chronic) manifestation had more than fourfold the risk of vascular events or death in 24 months of observation compared with controls with high atherothrombotic risk free of cerebrovascular events.",Cardiology;Internal medicine;Medicine;Neurology,"Staszewski, J.;Piusinska-Macoch, R.;Brodacki, B.;Skrobowska, E.;Macek, K.;Stepien, A.",2017,Nov,,0,
1112,Blood-brain barrier permeability in Alzheimer's disease: a case-control MRI study,"Blood-brain barrier (BBB) dysfunction may contribute to the risk of Alzheimer's disease (AD). Dynamic contrast-enhanced magnetic resonance imaging (MRI) was performed repeatedly nine times before and up to 30 min following a 20 ml Gd-DTPA bolus injection in 15 AD participants and 15 healthy older people. For each participant, small circular regions of interest (size: 9 voxels) were placed to sample widely the deep gray matter (12 regions), cortical gray matter (72 regions), white matter (72 regions) and CSF (8 regions) as well as the basilar and internal carotid arteries (3 regions). Data were analysed using mixed effects models. There was no overall significant difference for AD subjects versus controls, but there was a significant effect for the time-by-AD interaction. Estimated marginal means remained essentially unchanged in AD subjects, but increased slowly after 15 min in healthy controls. An initial rise in gray matter MRI signal intensity followed by a later increase was also seen in AD participants after adjusting for CSF MRI signal intensities. The data suggest that BBB permeability is present even at an early stage of AD. Though the extent of leakage was no greater than that of non-demented people of a similar age in this small sample, the temporal pattern differed, indicating different blood-brain-CSF compartmental kinetics.","Aged;Alzheimer Disease/ diagnosis/ physiopathology;Blood-Brain Barrier/ physiology;Brain/pathology;Case-Control Studies;Cerebral Cortex/pathology;Contrast Media/administration & dosage;Dominance, Cerebral/physiology;Female;Gadolinium DTPA;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology","Starr, J. M.;Farrall, A. J.;Armitage, P.;McGurn, B.;Wardlaw, J.",2009,Mar 31,10.1016/j.pscychresns.2008.04.003,0,
1113,Clinical assessment of 31 patients with Wilson's disease. Correlations with structural changes on magnetic resonance imaging,"Thirty-one patients with Wilson's disease were evaluated with detailed neurologic and medical examinations. Mean age (±SD) at onset was 21 ± 5 years and at examination was 28 ± 6 years. Of the 90% of patients who were first treated with penicillamine, 31% deteriorated initially despite therapy, and half never recovered to pretherapy baseline. At the time of our evaluations, the most common neurologic findings were dysarthria (97%), dystonia (65%), dysdiadochokinesia (58%), rigidity (52%), gait and postural abnormalities (42%), and tremor (32%). Chorea and dementia were rare. Twenty-two patients underwent magnetic resonance imaging. All but one of the 19 symptomatic patients had abnormal scans. The three asymptomatic patients had normal scans. Most lesions were seen in the caudate, putamen, subcortical white matter, midbrain, and pons. Generalized brain atrophy was also common. Lesions were less common in the thalamus, cerebellar vermis, midbrain tegmentum, globus pallidus, red nucleus, and dentate nucleus. Dystonia and bradykinesia correlated with putamen lesions, and dysarthria correlated with both putamen and caudate lesions.",,"Starosta-Rubinstein, S.;Young, A. B.;Kluin, K.",1987,1987,,0,
1114,Neuroimaging correlates of apathy and depression in Alzheimer's disease,"A consecutive series of 79 patients with probable Alzheimer's disease were assessed with a structured psychiatric evaluation, and diagnoses of apathy and depression were made using standardized criteria. Three-dimensional MRI scans were obtained from all patients, and images were segmented into gray matter, white matter, and CSF. White matter hyperintensities were edited on segmented images, and lobar assignments (frontal, temporal, parietal, and occipital) were made based on Talairach coordinates. Patients with apathy showed a significantly larger volume of frontal white matter hyperintensities than patients without apathy. Patients with depression had a significantly larger volume of right parietal white matter hyperintensities than patients without depression. However, neither apathy nor depression was significantly associated with lobar gray or white matter atrophy. Frontal and right parietal white matter hyperintensities are the strongest brain structural correlates of apathy and depression in Alzheimer's disease.","Affect;Aged;Alzheimer Disease/ pathology/ psychology;Analysis of Variance;Brain/ pathology;Depression/ pathology;Female;Frontal Lobe/pathology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Nerve Fibers, Unmyelinated/pathology;Organ Size;Parietal Lobe/pathology;Psychiatric Status Rating Scales","Starkstein, S. E.;Mizrahi, R.;Capizzano, A. A.;Acion, L.;Brockman, S.;Power, B. D.",2009,Summer,10.1176/jnp.2009.21.3.259,0,
1115,Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations,"See Charidimou (doi:10.1093/aww253) for a scientific commentary on this article. Cerebroretinal vasculopathy, hereditary vascular retinopathy, and hereditary endotheliopathy, retinopathy, nephropathy and stroke are neurovascular syndromes initially described as distinct entities. Recently they were shown to be one disease caused by C-terminal frame-shift mutations in TREX1, which was termed 'retinal vasculopathy with cerebral leukodystrophy'. Here we defined the genetic and clinicopathologic spectrum of this clinically and pathophysiologically poorly characterized and frequently misdiagnosed fatal neurovascular disorder. We identified five different TREX1 mutations in 78 members from 11 unrelated families and by using a standardized study protocol we retrospectively reviewed and aggregated the associated clinical, neuroimaging, and pathology data. Findings were similar across mutations and families. Sixty-four mutation carriers had vascular retinopathy. Neuroimaging revealed (i) punctate, hyperintense, white matter lesions with or without nodular enhancement in 97% of them; (ii) rim-enhancing mass lesions in 84%; and (iii) calcifications in the white matter in 52%. Ninety per cent had clinical manifestations of brain disease, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). One mutation carrier had enhancing brain lesions and neurological features but unknown retinopathy status. Additional systemic features included liver disease (78%), anaemia (74%), nephropathy (61%), hypertension (60%), mild Raynaud's phenomenon (40%), and gastro-intestinal bleeding (27%). Mean (± standard deviation) age at diagnosis was 42.9 ± 8.3 years and at death 53.1 ± 9.6 years. Pathological examination revealed systemic vasculopathy with luminal narrowing and multi-laminated basement membranes. The 13 mutation carriers without retinopathy or brain lesions were on average 8 years younger (mean age: 35.1 ± 10.6 years). Of them, 54% had mild Raynaud's phenomenon, 42% had migraine, and 23% had psychiatric disturbances. Retinal vasculopathy with cerebral leukodystrophy is an autosomal dominant systemic small-vessel disease due to specific TREX1 mutations and clinically primarily characterized by (i) visual impairment from vascular retinopathy; and (ii) neurological decline and premature death due to progressive enhancing cerebral white matter lesions. Impaired liver and kidney function, anaemia sometimes associated with gastrointestinal bleeding, hypertension, migraine, and Raynaud's phenomenon appear to be part of the clinical spectrum as well. Penetrance seems high. Because of the pathogenetic basis and the emerging clinical picture with systemic manifestations and conspicuous absence of leukodystrophy, we renamed the disease 'retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations'. We propose diagnostic criteria to facilitate clinical recognition and future studies.",adult;anemia;article;autosomal dominant inheritance;basement membrane;brain damage;brain disease;clinical feature;cognitive defect;controlled study;female;frameshift mutation;gastrointestinal hemorrhage;human;hypertension;kidney disease;leukodystrophy;liver disease;major clinical study;male;migraine;neuroimaging;neuropathology;nuclear magnetic resonance imaging;pathophysiology;priority journal;Raynaud phenomenon;retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestation;retinopathy;retrospective study;seizure;visual impairment;white matter lesion,"Stam, A. H.;Kothari, P. H.;Shaikh, A.;Gschwendter, A.;Jen, J. C.;Hodgkinson, S.;Hardy, T. A.;Hayes, M.;Kempster, P. A.;Kotschet, K. E.;Bajema, I. M.;Van Duinen, S. G.;Maat-Schieman, M. L. C.;De Jong, P. T. V. M.;De Smet, M. D.;De Wolff-Rouendaal, D.;Dijkman, G.;Pelzer, N.;Kolar, G. R.;Schmidt, R. E.;Lacey, J.;Joseph, D.;Fintak, D. R.;Grand, M. G.;Brunt, E. M.;Liapis, H.;Hajj-Ali, R. A.;Kruit, M. C.;Van Buchem, M. A.;Dichgans, M.;Frants, R. R.;Van Den Maagdenberg, A. M. J. M.;Haan, J.;Baloh, R. W.;Atkinson, J. P.;Terwindt, G. M.;Ferrari, M. D.",2016,,10.1093/brain/aww217,0,
1116,White matter damage in Alzheimer disease and mild cognitive impairment: assessment with diffusion-tensor MR imaging and parallel imaging techniques,"PURPOSE: To prospectively determine regional differences in fiber tract integrity between elderly patients with Alzheimer disease (AD), those with mild cognitive impairment (MCI), and healthy elderly subjects by using diffusion-tensor imaging with parallel imaging techniques and a new eight-element receiving coil. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Fifteen patients with AD (seven men, eight women; mean age; 68.8 years), 16 patients with MCI (nine men, seven women; mean age, 68.9 years) and 19 healthy control subjects (eight men, 11 women; mean age, 63.9 years) underwent diffusion-tensor imaging performed with a 1.5-T magnetic resonance system. An echo-planar imaging diffusion sequence was used with an integrated parallel acquisition technique (PAT) and an eight-element head coil. The mean apparent diffusion coefficient (ADC), fractional anisotropy (FA), and relative anisotropy (RA) values of several white matter (WM) regions were determined. The Kruskal-Wallis test was used initially to test for overall equality of median values in each data group. Single posttest comparisons were performed with the Mann-Whitney U test, with an overall statistical significance level of .05. RESULTS: FA and RA values were significantly (P < .05) decreased, whereas ADC values in the splenium of the corpus callosum were higher in patients with AD than in patients with MCI. Evidence of higher ADC values in the WM of the temporal lobe was observed in patients with AD compared with the ADC values in patients with MCI and in control subjects. ADC values in the parietal WM were significantly (P < .05) elevated in patients with MCI compared with those in control subjects. The images obtained with integrated PAT showed fewer susceptibility artifacts and were less distorted than images acquired without parallel imaging techniques. CONCLUSION: Reduced FA and RA values in patients with AD suggest that diffusion-tensor imaging of the brain can be used to confirm clinical manifestation of AD but is less applicable in the detection of MCI.","Aged;Alzheimer Disease/ diagnosis;Brain/ pathology;Cognition Disorders/ diagnosis;Demyelinating Diseases/ diagnosis;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Male;Reproducibility of Results;Sensitivity and Specificity","Stahl, R.;Dietrich, O.;Teipel, S. J.;Hampel, H.;Reiser, M. F.;Schoenberg, S. O.",2007,May,10.1148/radiol.2432051714,0,
1117,[Assessment of axonal degeneration on Alzheimer's disease with diffusion tensor MRI] Diffusion tensor imaging zur Erfassung axonaler Degeneration bei Morbus Alzheimer,"PURPOSE: Alzheimer disease (AD) causes cortical degeneration with subsequent degenerative changes of the white matter. The aim of this study was to investigate the extent of white matter tissue damage of patients with Alzheimer's disease in comparison with healthy subjects using diffusion tensor MRI (DTI). The value of integrated parallel imaging techniques (iPAT) for reduction of image distortion was assessed. MATERIAL AND METHODS: We studied 9 patients with mild AD and 10 age and gender matched healthy controls. DTI brain scans were obtained on a 1.5 tesla system (Siemens Magnetom Sonata) using parallel imaging (iPAT) and an EPI diffusion sequence with TE/TR 71 ms/6000 ms. We used an 8-element head coil and a GRAPPA reconstruction algorithm with an acceleration factor of 2. From the tensor, the mean diffusivity (D), the fractional anisotropy (FA), and the relative anisotropy (RA) of several white matter regions were determined. RESULTS: FA was significantly lower (p <0,05) in the white matter of the genu of corpus callosum from patients with AD than in the corresponding regions from healthy controls. There was a trend observed for slightly higher ADC values in the AD group (p=0,06). No significant changes were observed in the regions of the splenium, internal capsule, pericallosal areas, frontal, temporal, parietal, and occipital lobe. The images obtained with iPAT contained substantially less susceptibility artefacts and were less distorted than images acquired with non-parallel imaging technique. CONCLUSIONS: DTI is a method with potential to assess early stages of white matter damage in vivo. The altered FA and ADC values in the genu of corpus callosum of patients with AD presumably reflect the microscopic white matter degeneration. Acquisition time can be reduced by iPAT methods with less image distortion from susceptibility artefacts resulting in a more accurate calculation of the diffusion tensor.","Adult;Age Factors;Aged;Algorithms;Alzheimer Disease/ diagnosis/ pathology;Axons/ pathology;Brain/ pathology;Data Interpretation, Statistical;Female;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Models, Theoretical;Sex Factors","Stahl, R.;Dietrich, O.;Teipel, S.;Hampel, H.;Reiser, M. F.;Schoenberg, S. O.",2003,Jul,,0,
1118,Assessment of axonal degeneration on Alzheimer's disease with diffusion tensor MRI,"PURPOSE: Alzheimer disease (AD) causes cortical degeneration with subsequent degenerative changes of the white matter. The aim of this study was to investigate the extent of white matter tissue damage of patients with Alzheimer's disease in comparison with healthy subjects using diffusion tensor MRI (DTI). The value of integrated parallel imaging techniques (iPAT) for reduction of image distortion was assessed. MATERIAL AND METHODS: We studied 9 patients with mild AD and 10 age and gender matched healthy controls. DTI brain scans were obtained on a 1.5 tesla system (Siemens Magnetom Sonata) using parallel imaging (iPAT) and an EPI diffusion sequence with TE/TR 71 ms/6000 ms. We used an 8-element head coil and a GRAPPA reconstruction algorithm with an acceleration factor of 2. From the tensor, the mean diffusivity (D), the fractional anisotropy (FA), and the relative anisotropy (RA) of several white matter regions were determined. RESULTS: FA was significantly lower (p <0,05) in the white matter of the genu of corpus callosum from patients with AD than in the corresponding regions from healthy controls. There was a trend observed for slightly higher ADC values in the AD group (p=0,06). No significant changes were observed in the regions of the splenium, internal capsule, pericallosal areas, frontal, temporal, parietal, and occipital lobe. The images obtained with iPAT contained substantially less susceptibility artefacts and were less distorted than images acquired with non-parallel imaging technique. CONCLUSIONS: DTI is a method with potential to assess early stages of white matter damage in vivo. The altered FA and ADC values in the genu of corpus callosum of patients with AD presumably reflect the microscopic white matter degeneration. Acquisition time can be reduced by iPAT methods with less image distortion from susceptibility artefacts resulting in a more accurate calculation of the diffusion tensor.","Adult;Age Factors;Aged;Algorithms;Alzheimer Disease/ diagnosis/ pathology;Axons/ pathology;Brain/ pathology;Data Interpretation, Statistical;Female;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Models, Theoretical;Sex Factors","Stahl, R.;Dietrich, O.;Teipel, S.;Hampel, H.;Reiser, M. F.;Schoenberg, S. O.",2003,Jul,10.1007/s00117-003-0925-4,0,
1119,Brain volume and survival from age 78 to 85: the contribution of Alzheimer-type magnetic resonance imaging findings,"OBJECTIVES: To test the prediction of survival using magnetic resonance imaging (MRI)-derived global and regional brain volumes in subjects aged 78 to 79 without dementia. DESIGN: Observational follow-up study. SETTING: University teaching hospital. PARTICIPANTS: Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000. MEASUREMENTS: Vital status on May 12, 2006, global and regional brain volumes. RESULTS: Thirty-seven of 98 (34.9%) participants died during follow-up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1-7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P<.001), and sex (P=.004) were independent predictors of survival. CONCLUSION: In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/mortality/ pathology;Brain/ pathology;Chi-Square Distribution;Cluster Analysis;Comorbidity;Female;Follow-Up Studies;Geriatric Assessment/methods;Humans;Life Expectancy;Linear Models;Magnetic Resonance Imaging/ methods;Male;Organ Size;Predictive Value of Tests;Prognosis;Risk Assessment/methods;Scotland/epidemiology;Survival Analysis;Survival Rate","Staff, R. T.;Murray, A. D.;Ahearn, T.;Salarirad, S.;Mowat, D.;Starr, J. M.;Deary, I. J.;Lemmon, H.;Whalley, L. J.",2010,Apr,10.1111/j.1532-5415.2010.02765.x,0,
1120,Small vessel versus large vessel vascular dementia: Risk factors and MRI findings,"Objective: The aim of this study was a cross-sectional comparison of clinical and MRI characteristics and risk factor profiles between patients with small vessel disease (lacunae and white matter hyperintensities) and large vessel disease (large territorial or strategical infarcts) in a large cohort of VaD patients. Methods: Patients with VaD (NINDS-AIREN) were included in a large multicenter treatment trial (the VantagE study). All patients were examined by a neurologist and interviewed about their medical history. Based on MRI, patients were classified as having large vessel VaD, small vessel VaD, or a combination. Other MRI characteristics included white matter hyperintensities (WMH), medial temporal lobe atrophy (MTA) and general cortical atrophy. Results: Of the 706 patients, 522 (74 %) had small vessel disease, 126 (18 %) had large vessel disease and 58 (8 %) had both. Patients with small vessel disease were older and less educated, and showed more cortical and medial temporal lobe atrophy than patients with large vessel disease. The most prevalent vascular risk factors (hypertension, diabetes and smoking) were equally distributed between the different types of VaD. However, patients with large vessel disease had more hypercholesterolemia and cardiac risk factors compared to patients with small vessel disease. Conclusion: Cerebrovascular disease underlying VaD consists in the majority of small vessel disease and in about one fifth of large vessel disease. This study demonstrates heterogeneity between these two groups with regard to risk factor profile and atrophy scores on MRI. © 2008 Springer.",adult;aged;article;brain atrophy;brain damage;brain infarction;cardiovascular risk;controlled study;diabetes mellitus;disease classification;female;human;hypercholesterolemia;hypertension;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;risk factor;smoking;temporal lobe;white matter,"Staekenborg, S. S.;Van Straaten, E. C. W.;Van Der Flier, W. M.;Lane, R.;Barkhof, F.;Scheltens, P.",2008,,,0,
1121,Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease,"AIM: The authors investigated the prevalence of behavioural and psychological symptoms in vascular dementia (VaD) from baseline data of the VantagE study and compared the severity and relative frequency of symptoms between small-vessel VaD and large-vessel VaD. METHODS: Behavioural and psychological symptoms of 484 VaD patients included in a large multicentre clinical trial (registration number NCT00099216) were determined using the 12-item Neuropsychiatric Inventory (NPI). Symptoms were considered present when the score was > or =1. Based on MRI, patients were classified as having small-vessel VaD (83%) or large-vessel VaD (17%). RESULTS: Behavioural and psychological symptoms were reported in 92% of the VaD patients. The median NPI score of the total study population was 9 (0-76), with a median number of three symptoms per patient. Apathy (65%) was most prevalent, followed by depressive symptoms (45%), irritability (42%) and agitation/aggression (40%). Patients with small-vessel VaD reported more apathy, aberrant motor behaviour and hallucinations than patients with large-vessel VaD (p<0.05). In contrast, patients with large-vessel VaD reported a higher severity of agitation/aggression and euphoria (p<0.05). CONCLUSION: Behavioural and psychological symptoms are common in VaD. Patients with small-vessel and large-vessel VaD demonstrate different profiles of symptoms, with especially more apathy in small-vessel VaD and more agitation/agression in large-vessel VaD.","Capillaries [pathology];Cerebrovascular Circulation [physiology];Cerebrovascular Disorders [pathology];Cohort Studies;Dementia, Vascular [pathology] [psychology];Double-Blind Method;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Neuroprotective Agents [therapeutic use];Phenylcarbamates [therapeutic use];Rivastigmine;Socioeconomic Factors;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword]","Staekenborg, S. S.;Su, T.;Straaten, E. C.;Lane, R.;Scheltens, P.;Barkhof, F.;Flier, W. M.",2010,,10.1136/jnnp.2009.187500,0,
1122,Progression of mild cognitive impairment to dementia: contribution of cerebrovascular disease compared with medial temporal lobe atrophy,"BACKGROUND AND PURPOSE: We sought to determine the predictive value of magnetic resonance imaging measures of vascular disease (white matter hyperintensities [WMHs], lacunes, microbleeds, and infarcts) compared with atrophy on the progression of mild cognitive impairment to dementia. METHODS: We included 152 consecutive patients with mild cognitive impairment. Baseline magnetic resonance imaging was used to determine the presence of medial temporal lobe atrophy and vascular disease (presence of lacunes, microbleeds, and infarcts was determined, and WMHs were rated on a semiquantitative scale). Patients were followed up for 2+/-1 years. RESULTS: Seventy-two (47%) patients progressed to dementia during follow-up. Of these, 56 (37%) patients were diagnosed with Alzheimer's disease, and 16 (10%) patients were diagnosed with a non-Alzheimer dementia (including vascular dementia, frontotemporal lobar degeneration, and Parkinson dementia). Converters were older and had a lower Mini-Mental State Examination score at baseline. On baseline magnetic resonance imaging, patients who progressed to a non-Alzheimer dementia showed more severe WMHs and had a higher prevalence of lacunes in the basal ganglia and microbleeds compared with nonconverters. Cox proportional-hazard models showed that, adjusted for age and sex, baseline medial temporal lobe atrophy (hazard ratio=2.9; 95% CI, 1.7 to 5.3), but not vascular disease, was associated with progression to Alzheimer's disease. By contrast, deep WMHs (hazard ratio=5.7; 95% CI, 1.2 to 26.7) and periventricular hyperintensities (hazard ratio=6.5; 95% CI, 1.4 to 29.8) predicted progression to non-Alzheimer dementia. Furthermore, microbleeds (hazard ratio=2.6; 95% CI, 0.9 to 7.5) yielded a >2-fold increased, though nonsignificant, risk of non-Alzheimer dementia. CONCLUSIONS: Medial temporal lobe atrophy and markers of cerebrovascular disease predict the development of different types of dementia in mild cognitive impairment patients.","Aged;Aged, 80 and over;Atrophy;Basal Ganglia Cerebrovascular Disease/epidemiology/pathology/physiopathology;Cerebral Hemorrhage/epidemiology/pathology/physiopathology;Cognition Disorders/epidemiology/ pathology/physiopathology;Dementia, Vascular/epidemiology/ pathology/physiopathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Prevalence;Proportional Hazards Models;Risk Factors;Severity of Illness Index;Temporal Lobe/ pathology","Staekenborg, S. S.;Koedam, E. L.;Henneman, W. J.;Stokman, P.;Barkhof, F.;Scheltens, P.;van der Flier, W. M.",2009,Apr,10.1161/strokeaha.108.531343,0,
1123,Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobeatrophy in alzheimer's disease,"Background: The neuropathology of behavioural and psychological symptoms is much less understood than the neuropathology of cognitive impairment in AD. On MRI, medial temporal lobe atrophy (MTA) is presumed to reflect Alzheimer-type pathology. White matter hyperintensities (WMH) are considered markers of vascular pathology. Aim: We investigated differences in prevalence of behavioural and psychological symptoms in AD according to the presence of MTA and WMH on MRI. Methods: Behavioural and psychological symptoms of 111 consecutive AD patients were assessed using the Neuropsychatric Inventory (NPI). Symptoms were considered present when the score was ≥1. On MRI, MTA was rated using the five-point Scheltens-scale and WMH Using the four-point Fazekas-scale. Both MRI measures were dichotomised (MTA: absent 0/1, present 2-4; WMH absent 0/1, present 2/3). Results: Of the 111 AD patients, 60(55%) had MTA, and 32(29%) had WMH. The presence of MTA was associated with the presence of WMH (χ 2 = 11.8, p < 0.001). The prevalence of behavioural and psychological symptom - defined as a NPI score of ≥1 on at least one symptom - was 74%. The median NPI score of the total study population was 6(0-41). There was no difference in prevalence according to MTA (p = 0.53) or WMH (p = 0.18). On inspection of individual NPI items, neither MTA, nor WMH was related to any of the symptoms. Conclusions: There were no differences in prevalence of behavioural and psychological symptoms according to MTA or WMH, as rated on MRI. This suggests that the occurrence of those symptoms depends on other determinants, such as coping style or genetic make-up. Copyright © 2007 John Wiley & Sons, Ltd.",adult;aged;agitation;Alzheimer disease;anxiety disorder;apathy;article;behavior disorder;brain atrophy;chi square test;controlled study;coping behavior;delusion;depression;disease association;euphoria;female;hallucination;human;irritability;major clinical study;male;mental disease;neuropsychological test;nuclear magnetic resonance imaging;prevalence;scoring system;statistical significance;temporal lobe;white matter,"Staekenborg, S. S.;Gillissen, F.;Romkes, R.;Pijnenburg, Y. A. L.;Barkhof, F.;Scheltens, P.;van der Flier, W. M.",2008,,,0,
1124,Neurological signs in relation to type of cerebrovascular disease in vascular dementia,"BACKGROUND AND PURPOSE: The aim of this study was to describe the prevalence of a number of neurological signs in a large population of patients with vascular dementia (VaD) and to compare the relative frequency of specific neurological signs dependent on type of cerebrovascular disease. METHODS: Seven hundred six patients with VaD (NINDS-AIREN) were included from a large multicenter clinical trial (registration number NCT00099216). At baseline neurological examination, the presence of 16 neurological signs was assessed. Based on MRI, patients were classified as having large vessel VaD (18%; large territorial or strategical infarcts on MRI), small vessel VaD (74%; white matter hyperintensities [WMH], multiple lacunes, bilateral thalamic lesions on MRI), or a combination of both (8%). RESULTS: A median number of 4.5 signs per patient was presented (maximum 16). Reflex asymmetry was the most prevalent symptom (49%), hemianopia was most seldom presented (10%). Measures of small vessel disease were associated with an increased prevalence of dysarthria, dysphagia, parkinsonian gait disorder, rigidity, and hypokinesia and as well to hemimotor dysfunction. By contrast, in the presence of a cerebral infarct, aphasia, hemianopia, hemimotor dysfunction, hemisensory dysfunction, reflex asymmetry, and hemiplegic gait disorder were more often observed. CONCLUSIONS: The specific neurological signs demonstrated by patients with VaD differ according to type of imaged cerebrovascular disease. Even in people who meet restrictive VaD criteria, small vessel disease is often seen with more subtle signs, including extrapyramidal signs, whereas large vessel disease is more often related to lateralized sensorimotor changes and aphasia.","Aphasia [epidemiology] [pathology];Basal Ganglia Diseases [epidemiology] [pathology];Brain Infarction [epidemiology] [pathology];Cerebrovascular Circulation;Cholinesterase Inhibitors [therapeutic use];Dementia, Vascular [drug therapy] [epidemiology] [pathology];Gait Disorders, Neurologic [epidemiology] [pathology];Hemianopsia [epidemiology] [pathology];Magnetic Resonance Imaging;Movement Disorders [epidemiology] [pathology];Phenylcarbamates [therapeutic use];Prevalence;Reflex, Abnormal;Rivastigmine;Thalamus [pathology];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Staekenborg, S. S.;Flier, W. M.;Straaten, E. C.;Lane, R.;Barkhof, F.;Scheltens, P.",2008,,10.1161/strokeaha.107.493353,0,
1125,Neurological signs in relation to white matter hyperintensity volumes in memory clinic patients,"PURPOSE: To determine the frequency of neurological signs in a memory clinic population and to explore their associations with white matter hyperintensity (WMH). METHODS: We included patients with Alzheimer disease (AD; n = 210), vascular dementia (VaD; n = 34), mild cognitive impairment (MCI; n = 86) and subjective complaints (n = 153). The presence of extrapyramidal and unilateral signs was assessed from medical charts. On MRI, WMH volumes were extracted automatically. RESULTS: Extrapyramidal signs were found in 10% and unilateral signs in 12% of the patients. Age- and sex-adjusted extrapyramidal signs occurred more often in VaD compared to patients with subjective complaints. Unilateral signs were more prevalent in all groups compared to patients with subjective complaints. Two-way analysis of variance (ANOVA) with WMH as the dependent variable showed a main effect of diagnosis (p < 0.001), but not of extrapyramidal signs (p = 0.62). In contrast, 2-way ANOVA showed main effects of diagnosis (p < 0.001) and unilateral signs (p = 0.001). Furthermore, there was an interaction between these factors (p = 0.04); if unilateral signs were present, patients with subjective complaints and VaD showed more WMH, whereas there was no relation in AD and MCI. CONCLUSION: Extrapyramidal and unilateral signs are common in memory clinic patients, but are only modestly related to WMH.","Aged;Aged, 80 and over;Alzheimer Disease/complications/diagnosis;Analysis of Variance;Basal Ganglia Diseases/complications/diagnosis;Brain/*pathology;Cognition Disorders/complications/diagnosis;Dementia, Vascular/complications/diagnosis;Female;Humans;*Magnetic Resonance Imaging;Male;Medical Records;Memory Disorders/*complications/*diagnosis;Middle Aged;Nervous System Diseases/*complications/*diagnosis","Staekenborg, S. S.;de Waal, H.;Admiraal-Behloul, F.;Barkhof, F.;Reiber, J. H.;Scheltens, P.;Pijnenburg, Y. A.;Vrenken, H.;van der Flier, W. M.",2010,,10.1159/000254791,0,
1126,Cognitive symptoms of chronic disorders of cerebral circulation in patients with atrial fibrillation,"Atrial fibrillation is a heart rhythm disorder, accompanied by numerous systemic disorders. One of them accounting for changes in the central nervous system is of great importance. Reduction of cardiac output and contractile function of the heart cause a deterioration of cerebral blood flow, thus contributing to the formation and progression of cognitive disorders that subsequently can lead to dementia. The objective of this study was to investigate clinical manifestations of chronic cerebrovascular pathology in patients with different clinical forms of atrial fibrillation based on neuropsychological studies. Eighty two patients with atrial fibrillation nonvalvular etiology, developed due to coronary heart disease, were examined. The comparison group consisted of 30 patients with ischemic heart disease without any cardiac rhythm and conduction. Patients in both groups underwent a computed tomography examination of the brain. The study established that cognitive disorders in patients with atrial fibrillation were manifested in attention deficit, reduced rate of speech and mental activity, impaired visual-spatial functions and secondary memory disorders. The permanent form of atrial fibrillation showed accelerated decrease in the speed of psychomotor reactions, visual-spatial disorders and memory loss, whereas deterioration of cognitive functions occurs regardless of age, duration of hypertension, and predictors of dyslipidemic disorders. The presence of atrial fibrillation is associated with a higher incidence of diffuse lesions of the white matter of the brain. The most pronounced changes in patients with atrial fibrillation are detected in the periventricular matter and perivascular spaces. The progression of diffuse changes of the white matter of the brain associated with the increase of memory disorders, attention and mental speed. Thus, early manifestations of chronic disorders of cerebral circulation in patients with atrial fibrillation in the absence of severe focal neurological symptoms may be mild cognitive disorders, whose identification is necessary due to the increased risk of progression to the stage of severe cognitive deficits.",adult;aged;amnesia;article;atrial fibrillation;attention deficit disorder;cerebrovascular disease;chronic disease;cognitive defect;computer assisted tomography;controlled study;disease duration;dyslipidemia;female;human;hypertension;ischemic heart disease;major clinical study;male;memory disorder;mental performance;middle aged;psychomotor disorder;speech;white matter lesion,"Stadnik, S. N.",2015,,,0,
1127,"Distinct brain volume changes correlating with clinical stage, disease progression rate, mutation size, and age at onset prediction as early biomarkers of brain atrophy in Huntington's disease","Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain-derived-neurotrophic-factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone-of-onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R(2)= 0.25, P < 0.0001).",Adolescent;Adult;Age of Onset;Aged;Atrophy;Brain/ pathology;Disease Progression;Female;Humans;Huntington Disease/genetics/ pathology;Male;Middle Aged;Mutation;Trinucleotide Repeats,"Squitieri, F.;Cannella, M.;Simonelli, M.;Sassone, J.;Martino, T.;Venditti, E.;Ciammola, A.;Colonnese, C.;Frati, L.;Ciarmiello, A.",2009,Winter,10.1111/j.1755-5949.2008.00068.x,0,
1128,High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population,"OBJECTIVE:: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (Sao Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS:: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). RESULTS:: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002). CONCLUSIONS:: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.",Age Factors;Aged;Analysis of Variance;Asymptomatic Diseases/ epidemiology;Brain Infarction/ complications/ epidemiology/physiopathology;Brazil/epidemiology;Cognitive Dysfunction/ epidemiology/ etiology/physiopathology;Female;Humans;Intelligence Tests;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prevalence;Psychiatric Status Rating Scales;Reference Values;Risk Assessment;Risk Factors;Socioeconomic Factors,"Squarzoni, P.;Tamashiro-Duran, J. H.;Duran, F. L. S.;Leite, C. C.;Wajngarten, M.;Scazufca, M.;Menezes, P. R.;Lotufo, P. A.;Alves, Tctf;Busatto, G. F.",2017,Aug,,0,
1129,Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial),"BACKGROUND AND PURPOSE-: In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. METHODS-: We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. RESULTS-: Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. CONCLUSIONS-: We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. CLINICAL TRIAL REGISTRATION-: URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. Copyright 2016 American Heart Association, Inc.",atrial fibrillation;brain ischemia;cancer size;clinical trial;computer assisted tomography;confidence interval;controlled clinical trial;controlled study;death;disability;human;infarction;insula;major clinical study;mortality;multivariate logistic regression analysis;neuroimaging;nuclear magnetic resonance;odds ratio;randomization;randomized controlled trial,"Sposato, L. A.;Cohen, G.;Wardlaw, J. M.;Sandercock, P.;Lindley, R. I.;Hachinski, V.",2017,,,0,
1130,Biochemical markers of neurodegeneration in hereditary diffuse leucoencephalopathy with spheroids,"Hereditary diffuse leucoencephalopathy with spheroids (HDLS) is a rare autosomal dominantly inherited disease with unknown pathophysiology. Diagnosis of neurodegenerative diseases is increasingly based on biomarkers. Although lumbar puncture is routinely performed during the diagnostic workup of HDLS, reports on alterations of neurodegeneration-specific biochemical markers have not been documented so far. We report a 35-year-old woman with clinical, radiological and neuropathological signs of HDLS. She suffered from a rapidly progressive frontal lobe syndrome. Brain MRI revealed diffuse leucoencephalopathy with predominant involvement of the periventricular white matter and corpus callosum. Although she was severely impaired and leucoencephalopathy was prominent, only cerebrospinal fluid total-τ was moderately elevated. Other markers of neuronal (NSE) and astrocytic (S100B) damage were within normal range. Therefore, biochemical markers of central nervous system damage are not helpful in the diagnosis of HDLS. Copyright 2014 BMJ Publishing Group. All rights reserved.",biological marker;methylprednisolone;neuron specific enolase;protein 14 3 3;protein S100B;tau protein;adult;anamnesis;apraxia;article;ataxia;bradykinesia;brain biopsy;case report;cerebrospinal fluid analysis;corpus callosum;cyanocobalamin deficiency;degenerative disease;depression;disorientation;dysmetria;dystonia;familial diffuse leukoencephalopathy;feces incontinence;female;folic acid deficiency;gait disorder;hospital readmission;human;hyperferritinemia;hyperreflexia;hypothalamus periventricular nucleus;leukodystrophy;leukoencephalopathy;limb weakness;memory disorder;mental deterioration;Mini Mental State Examination;multiple sclerosis;nerve cell lesion;nerve degeneration;neuroaxonal dystrophy;neuroimaging;neurologic disease;neuropathology;nuclear magnetic resonance imaging;priority journal;progressive frontal lobe syndrome;spheroid cell;steroid therapy;tendon reflex;urine incontinence;walking difficulty;white matter,"Spitzer, P.;Kohl, Z.;Gölitz, P.;Coras, R.;Blümcke, I.;Brück, W.;Dörfler, A.;Maihöfner, C.",2014,,,0,
1131,Unusual clinical presentations in subjects carrying novel NOTCH3 gene mutations,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a disease caused by alterations in the NOTCH3 gene. Methods: We describe the clinical, instrumental, and genetic findings in CADASIL patients who carry novel NOTCH3 gene mutations. Results and conclusions: This study broadens the spectrum of clinical manifestations and genetic alterations associated with this disease. © 2013 by National Stroke Association.",analgesic agent;Notch3 receptor;adult;article;CADASIL;case report;exon;female;gene mutation;genetic association;headache;human;male;memory disorder;mental instability;mild cognitive impairment;monoparesis;nausea and vomiting;neuroimaging;nuclear magnetic resonance imaging;paresis;priority journal;sensation;vertigo;vestibulocochlear nerve disease;visual impairment;white matter,"Spinicci, G.;Conti, M.;Cherchi, M. V.;Mancosu, C.;Murru, R.;Carboni, N.",2013,,,0,
1132,A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia,"Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and DaT-scan with 123I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of 18F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca’s area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.",fluorodeoxyglucose f 18;ioflupane i 123;adult;article;brain atrophy;case report;clinical feature;cognition;controlled study;corticobasal degeneration;diffusion tensor imaging;female;functional magnetic resonance imaging;human;middle aged;multimodal imaging;neuroimaging;positron emission tomography;primary progressive aphasia;priority journal;progressive nonfluent aphasia;superior longitudinal fasciculus;tractography;white matter;Intera,"Spinelli, E. G.;Caso, F.;Agosta, F.;Gambina, G.;Magnani, G.;Canu, E.;Blasi, V.;Perani, D.;Comi, G.;Falini, A.;Gorno-Tempini, M. L.;Filippi, M.",2015,,,0,
1133,The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family,"Multiple system tauopathy with presenile dementia (MSTD) is an inherited disease caused by a (g) to (a) transition at position +3 in intron 10 of Tau. It belongs to the spectrum of frontotemporal dementia and parkinsonism linked to chromosome 17 with mutations in Tau (FTDP-17T). Here we present the longitudinal clinical, neuropsychological, neuroimaging, neuropathological, biochemical and genetic characterization of the MSTD family. Presenting signs were consistent with the behavioural variant of frontotemporal dementia in 17 of 21 patients. Two individuals presented with an atypical form of progressive supranuclear palsy and two others with either severe postural imbalance or an isolated short-term memory deficit. Memory impairment was present at the onset in 15 patients, with word finding difficulties and stereotyped speech also being common. Parkinsonism was first noted 3 years after the onset of symptoms. Neuroimaging showed the most extensive grey matter loss in the hippocampus, parahippocampal gyrus and frontal operculum/insular cortex of the right hemisphere and, to a lesser extent, in the anterior cingulate gyrus, head of the caudate nucleus and the posterolateral orbitofrontal cortex and insular cortex bilaterally. Neuropathologically, progressive nerve cell loss, gliosis and coexistent neuronal and/or glial deposits consisting mostly of 4-repeat tau were present in frontal, cingulate, temporal and insular cortices, white matter, hippocampus, parahippocampus, basal ganglia, selected brainstem nuclei and spinal cord. Tau haplotyping indicated that specific haplotypes of the wild-type allele may act as modifiers of disease presentation. Quantitative neuroimaging has been used to analyse the progression of atrophy in affected individuals and for predicting disease onset in an asymptomatic mutation carrier. This multidisciplinary study provides a comprehensive description of the natural history of disease in one of the largest known families with FTDP-17T.","Adult;Alzheimer Disease/genetics/metabolism/pathology/psychology;Brain/metabolism/pathology;Brain Mapping/methods;Cognition Disorders/etiology/pathology;Disease Progression;Female;Humans;Introns/genetics;Magnetic Resonance Imaging;Male;Middle Aged;*Mutation;Neuropsychological Tests;Pedigree;Retrospective Studies;Supranuclear Palsy, Progressive/genetics/metabolism/pathology/psychology;Tauopathies/*genetics/metabolism/pathology/psychology;tau Proteins/*genetics/metabolism","Spina, S.;Farlow, M. R.;Unverzagt, F. W.;Kareken, D. A.;Murrell, J. R.;Fraser, G.;Epperson, F.;Crowther, R. A.;Spillantini, M. G.;Goedert, M.;Ghetti, B.",2008,Jan,10.1093/brain/awm280,0,
1134,Late-onset dementia: structural brain damage and total cerebral blood flow,"PURPOSE: To prospectively compare indicators of structural brain damage and total cerebral blood flow in patients with late-onset dementia, subjects of the same age with optimal cognitive function, and young subjects. MATERIALS AND METHODS: The institutional ethics committee approved the studies, and all participants (or their guardians) gave informed consent. The test group included 17 patients older than 75 years (four men, 13 women; median age, 83 years) and with a diagnosis of dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The control group included 16 subjects (four men, 12 women; median age, 87 years) with optimal cognitive function, who were selected from among 599 elderly subjects enrolled in a population-based follow-up study, and 15 young healthy subjects (seven men, eight women; median age, 29 years). Measurements of intracranial and total brain volumes, structural brain damage, and cerebral blood flow were obtained with magnetic resonance imaging. Mean values were compared with the t test; medians, with the Mann-Whitney U test. RESULTS: Values for total brain volume were significantly smaller in elderly subjects (P < .001) but did not differ significantly between patients with dementia and subjects of the same age with optimal cognitive function (P = .69). Among the elderly, significantly higher scores for number and extent of white matter areas of signal hyperintensity (P = .028) and lower magnetization transfer ratios (P = .016) indicated greater structural brain damage in those with dementia. Cerebral blood flow was 246 mL/min lower (P < .001) in elderly subjects than in young subjects. In patients with dementia, cerebral blood flow was 108 mL/min lower than that in subjects of the same age with optimal cognitive function (551 vs 443 mL/min, P < .001). CONCLUSION: The combined observations of more structural brain damage and lower cerebral blood flow in demented elderly individuals than in subjects of the same age with optimal cognitive function support the hypothesis that vascular factors contribute to dementia in old age.","Aged;Aged, 80 and over;Aging/ physiology;Cerebrovascular Circulation/ physiology;Dementia/ pathology/physiopathology;Female;Humans;Logistic Models;Magnetic Resonance Imaging/ methods;Male;Prospective Studies;Statistics, Nonparametric","Spilt, A.;Weverling-Rijnsburger, A. W.;Middelkoop, H. A.;van Der Flier, W. M.;Gussekloo, J.;de Craen, A. J.;Bollen, E. L.;Blauw, G. J.;van Buchem, M. A.;Westendorp, R. G.",2005,Sep,10.1148/radiol.2363041454,0,
1135,Not all age-related white matter hyperintensities are the same: a magnetization transfer imaging study,"PURPOSE: Our aim was to assess whether presumed histologic heterogeneity of age-related white matter hyperintensities (WMH) is reflected in quantitative magnetization transfer imaging measures. MATERIALS AND METHODS: From a group of patients participating in a double-blind placebo-controlled multicenter study on the effect of pravastatin (PROSPER), we selected 56 subjects with WMH. WMH were classified as periventricular WMH (PVWMH) and deep WMH (DWMH). PVWMH were subclassified as irregular or smooth, depending on the aspect of their border. Signal intensity of WMH on T1-weighted images was scored as iso- or hypointense. The mean magnetization transfer ratio (MTR) value of different types of WMH was assessed and compared. As a control group, we selected 19 subjects with no or limited WMH. RESULTS: Mean (SE) MTR of PVWMH (frontal, 31.2% [0.2%]; occipital, 32.2% [0.2%]) was lower than that of DWMH (33.7% [0.5%]). The mean MTR of frontal PVWMH (31.2% [0.2%]) was lower than that of occipital PVWMH (32.2% [0.2%]). Compared with occipital PVWMH, frontal PVWMH more often had a smooth lining (72% frontal versus 8% occipital) and an area with low signal intensity on T1-weighted images (76% frontal versus 35% occipital). MTR did not differ between smooth (31.1% [0.3%]) and irregular (31.6% [0.5%]) PVWMH. CONCLUSION: Age-related WMH are heterogeneous, despite their similar appearance on T2-weighted images. By taking into account heterogeneity of age-related WMH, both in terms of etiology and in terms of severity of tissue destruction, one may obtain better understanding on the causes and consequences of these lesions.","Age Factors;Anticholesteremic Agents [therapeutic use];Cerebral Cortex [pathology];Cerebral Ventricles [pathology];Cognition Disorders [diagnosis] [drug therapy];Dementia, Vascular [diagnosis] [drug therapy];Dominance, Cerebral [physiology];Double-Blind Method;Frontal Lobe [pathology];Hydroxymethylglutaryl-CoA Reductase Inhibitors [therapeutic use];Image Enhancement;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Occipital Lobe [pathology];Pravastatin [therapeutic use];Prospective Studies;Reference Values;Statistics as Topic;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-stroke","Spilt, A.;Goekoop, R.;Westendorp, R. G.;Blauw, G. J.;Craen, A. J.;Buchem, M. A.",2006,,,0,
1136,Psychometric limitations of the mini-mental state examination among nondemented older adults: An evaluation of neurocognitive and magnetic resonance imaging correlates,"Background/Study Context: Although many of the Mini-Mental State Examination's (MMSE) limitations are well accepted among geriatricians, neuropsychologists, and other interested clinicians and researchers, its continued use in psychometrically unsound ways suggests that additional investigation and dissemination of information are sorely needed. The authors aimed to describe the reliability and validity of the MMSE as a measure of cognitive function among healthy older adults. Methods: The authors examined MMSE performance in 124 stroke-and dementia-free, community-dwelling older adults (65% male; mean age = 66.5 years). All participants were administered an extensive neuropsychological battery composed of measures of attention, executive function, memory, and visuospatial function. A subset of 99 participants also underwent magnetic resonance imaging (MRI). MMSE test-retest reliability was examined among 65 participants who underwent repeat MMSE testing over an average interval of 83.2 days. Results: Spearman test-retest correlation for total MMSE scores was r(S) =.35 (p =.004), for Serial Sevens was r(S) =.40 (p =.001), and for Word Recall was r(S) =-.01 (p =.96). Total MMSE performance correlated significantly with a minority of neuropsychological tests and MRI-derived indices of white matter disease and brain atrophy. A subset of 17% of participants demonstrated inappropriate intrusion of MMSE Pentagon Copy during another test of visuospatial recall. Conclusions: Overall, MMSE scores exhibited ceiling effects, poor test-retest reliability, limited sensitivity to subtle brain abnormalities, and a high rate of intrusion elsewhere in the neuropsychological battery. Individual MMSE items demonstrated poor construct validity. These qualities illustrate the serious limitations of the MMSE in detecting individual differences in cognitive function among healthy older adults. © 2013 Taylor and Francis Group, LLC.",,"Spencer, R. J.;Wendell, C. R.;Giggey, P. P.;Katzel, L. I.;Lefkowitz, D. M.;Siegel, E. L.;Waldstein, S. R.",2013,1,,0,
1137,Quantitative evaluation of MRI and histological characteristics of the 5xFAD Alzheimer mouse brain,"Assessment of beta-amyloid (Abeta) plaque load in Alzheimer's disease by MRI would provide an important biomarker to monitor disease progression or treatment response. Alterations in tissue structure caused by the presence of Abeta may cause localised changes that can be detected by quantitative T(1) and T(2) relaxation time measurements averaged over larger areas of tissue than that of individual plaques. We constructed depth profiles of the T(1) and T(2) relaxation times of the cerebral cortex with subjacent white matter and hippocampus in six 5xFAD transgenic and six control mice at 11 months of age. We registered these profiles with corresponding profiles of three immunohistochemical markers: beta-amyloid; neuron-specific nuclear protein (NeuN), a marker of neuronal cell load; and myelin basic protein (MBP), a marker of myelin load. We found lower T(1) in the 5xFAD transgenic mice compared to wild type control mice at all depths, with maximum sensitivity for detection at specific layers. T(1) negatively correlated with Abeta staining intensity in the 5xFAD mice which had no changes in NeuN and MBP staining compared to wild type mice. We postulate that these relaxation time changes are due to the presence of beta-amyloid in the transgenic mice. It may be clinically feasible to develop a similar layered analysis protocol as a biomarker for Alzheimer's disease in humans.","Alzheimer Disease/metabolism/*pathology;Animals;Brain/metabolism/*pathology;Disease Models, Animal;Image Processing, Computer-Assisted;Immunohistochemistry;Magnetic Resonance Imaging/*methods;Mice;Mice, Transgenic","Spencer, N. G.;Bridges, L. R.;Elderfield, K.;Amir, K.;Austen, B.;Howe, F. A.",2013,Aug 1,10.1016/j.neuroimage.2013.02.071,0,
1138,Photosensitivity is an early marker of neuronal ceroid lipofuscinosis type 2 disease,"Objective: This study aimed to identify early clinical, magnetic resonance imaging (MRI), and electroencephalographic (EEG) characteristics of neuronal ceroid lipofuscinosis type 2 (CLN2) disease to enable early diagnosis, thus providing the key to early treatment, and optimized care and outcomes. Methods: Retrospective clinical chart review of a series of patients diagnosed with CLN2 disease from 2005 to 2015 at a single center in Italy. Clinical, MRI, and EEG findings were reviewed. Results: A total of 14 patients were included. For the whole group, median (range) age at disease onset was 3.0 (2.0–3.8) years. Epilepsy was the most commonly reported presenting symptom (in 50% [seven of 14] of patients), occurring at the age of 3.2 (2.6–3.8) years. First seizure was myoclonic in 36% (five of 14) of patients, followed by generalized tonic–clonic in 29% (4 of 14), atonic in 22% (three of 14), and focal with motor signs in 14% (two of 14). All patients walked independently at the age of 12.0 (11.0–18.0) months, but delayed speech or regression of acquired verbal skills was present in 100% of patients at 3 years. EEGs revealed a photoparoxysmal response (PPR) on intermittent photic stimulation in 93% (13 of 14) of patients. PPR was present from the first EEG, which was performed at 3.6 (3.1–4.0) years, in 43% (six of 14) of patients; it was documented at low (1–3 Hz) stimulation frequencies in 69% (nine of 13) and took the form of a flash-per-flash response in 69% (nine of 13). First brain MRI at the age of 3.8 (3.0–5.1) years revealed cerebellar atrophy in 100% (14 of 14) of patients and alteration of the periventricular white matter signal in the posterior hemispheric region in 79% (11 of 14). Significance: Early photosensitivity (typically PPR at low stimulation frequencies of 1–3 Hz) is a hallmark of CLN2 disease. This diagnosis should be considered in a child presenting with any type of seizure, and particularly if it is accompanied by delayed speech and/or ataxia or MRI abnormalities (posterior white matter signal alteration or cerebellar atrophy).",valproic acid;adolescent;article;ataxia;balance disorder;cerebellum atrophy;child;clinical article;controlled study;early diagnosis;electroencephalography;female;follow up;human;Italy;male;medical record review;myoclonus seizure;neuronal ceroid lipofuscinosis;neuronal ceroid lipofuscinosis type 2;nuclear magnetic resonance imaging;outcome assessment;perinatal asphyxia;photosensitivity;preschool child;priority journal;school child;speech delay;stroboscopy;visual evoked potential;white matter,"Specchio, N.;Bellusci, M.;Pietrafusa, N.;Trivisano, M.;de Palma, L.;Vigevano, F.",2017,,10.1111/epi.13820,0,
1139,Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer's disease patients: A neuroimaging biomarker of the disease,"Purpose The objective of this study was to correlate the presence and distribution of cerebral microbleeds in Alzheimer's disease patients with cerebrospinal fluid biomarkers (amyloid-beta and phosphorylated tau 181 protein levels) and cognitive decline by using susceptibility-weighted imaging magnetic resonance sequences at 1.5 T. Material and methods Fifty-four consecutive Alzheimer's disease patients underwent brain magnetic resonance imaging at 1.5 T to assess the presence and distribution of cerebral microbleeds on susceptibility-weighted imaging images. The images were analyzed in consensus by two neuroradiologists, each with at least 10 years' experience. Dementia severity was assessed with the Mini-Mental State Examination score. A multiple regression analysis was performed to assess the associations between the number and location of cerebral microbleed lesions with the age, sex, duration of the disease, cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels, and cognitive functions. Results A total of 296 microbleeds were observed in 54 patients; 38 patients (70.4%) had lobar distribution, 13 patients (24.1%) had non-lobar distribution, and the remaining three patients (5.6%) had mixed distribution, demonstrating that Alzheimer's disease patients present mainly a lobar distribution of cerebral microbleeds. The age and the duration of the disease were correlated with the number of lobar cerebral microbleeds ( P < 0.001). Cerebrospinal fluid amyloid-beta, phosphorylated tau 181 protein levels, and cognitive decline were correlated with the number of lobar cerebral microbleeds in Alzheimer's disease patients ( P < 0.001). Conclusion Lobar distribution of cerebral microbleeds is associated with Alzheimer's disease and the number of lobar cerebral microbleeds directly correlates with cerebrospinal fluid amyloid-beta and phosphorylated tau 181 protein levels and with the cognitive decline of Alzheimer's disease patients.",0 (Amyloid beta-Peptides);0 (Biomarkers);0 (tau Proteins);Aged;Alzheimer Disease/ diagnostic imaging;Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Cerebral Hemorrhage/ diagnostic imaging;Female;Humans;Magnetic Resonance Imaging/ methods;Male;tau Proteins/cerebrospinal fluid;Alzheimer's disease;Cerebral microbleeds;magnetic resonance imaging;susceptibility-weighted imaging,"Sparacia, G.;Agnello, F.;La Tona, G.;Iaia, A.;Midiri, F.;Sparacia, B.",2017,Aug,,0,
1140,Neuropsychological analysis of a case of abrupt onset mirror sign following a hypotensive crisis in a patient with vascular dementia,"The mirror sign is a delusional misidentification symptom (DMS) characterized by an inability to recognize one's own image in the mirror, often in the presence of an intact ability to recognize others in the mirror. The symptom has been only sparsely reported previously, and primarily within the Alzheimer's disease literature. A case is reported of an 82-year-old female with abrupt onset of mirror sign following a hypotensive crisis. Neuroradiographic studies revealed periventricular white matter change in the bifrontal and bilateral parietal occipital regions, right greater than left, as well as scattered lacunar infarcts. The patient was unable to recognize herself in the mirror and became progressively paranoid in response to 'the stranger in the mirror'. However, there was no evidence of prosopagnosia and she was able to recognize others in the mirror. Results from the neurobehavioral examinations replicated a previous report of mirror sign, and were consistent with those reported for other DMS. The acute onset, vascular changes on MRI, and lateralized neuropsychological findings suggested a right hemisphere-based visual associative etiology to the mirror sign.",,"Spangenberg, K. B.;Wagner, M. T.;Bachman, D. L.",1998,1998,,0,
1141,Brain microstructure of subclinical apathy phenomenology in healthy individuals,"Although apathy has been extensively studied in relation to neuropsychiatric disorders, it is still unclear whether, in healthy people, it should be considered as a physiological phenomenon or whether it is a risk factor for progression to clinical disturbances. Here, we investigated subclinical apathy phenomenology and its brain microstructural correlates in healthy individuals. We submitted 72 participants to a comprehensive clinical assessment, a high-resolution structural MRI and a diffusion tensor imaging scan protocol. Data of individual microstructural (mean diffusivity and fractional anisotropy) variations were processed across genders in relation to the Apathy Rating Scale score. In females, subclinical apathy phenomenology was associated with microstructural variation of the bilateral thalami, the anterior thalamic radiation, the forceps major, and the corona radiate. These are white matter areas mostly connecting the thalami to the frontal and occipital cortices, regions that are known to be implicated in the expression of apathy in clinical samples. No significant relationship with brain microstructure was found in males who showed a positive correlation between subclinical apathy and somatic phenomenology of depression. In conclusion, our results show that in healthy individuals subclinical apathy phenomenology is associated with different mechanisms across genders, and raise the issue about whether brain microstructural changes associated with subclinical apathy in healthy females could be a precocious marker useful in the prediction of progression to more severe apathetic conditions.© 2012 Wiley Periodicals, Inc.",,"Spalletta, G.;Fagioli, S.;Caltagirone, C.;Piras, F.",2013,December,,0,
1142,"A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates","Subcortical white matter stroke is a common stroke subtype but has had limited pre-clinical modeling. Recapitulating this disease process in mice has been impeded by the relative inaccessibility of the subcortical white matter arterial supply to induce white matter ischemia in isolation. In this report, we detail a subcortical white matter stroke model developed in the mouse and its characterization with a comprehensive set of MRI, immunohistochemical, neuronal tract tracing and electron microscopic studies. Focal injection of the vasoconstrictor endothelin-1 into the subcortical white matter produces an infarct core that develops a maximal MRI signal by day 2, which is comparable in relative size and location to human subcortical stroke. Immunohistochemical studies indicate that oligodendrocyte apoptosis is maximal at day 1 and apoptotic cells extend away from the stroke core into the peri-infarct white matter. The amount of myelin loss exceeds axonal fiber loss in this peri-infarct region. Activation of microglia/macrophages takes place at 1 day after injection near injured axons. Neuronal tract tracing demonstrates that subcortical white matter stroke disconnects a large region of bilateral sensorimotor cortex. There is a robust glial response after stroke by BrdU pulse-labeling, and oligodendrocyte precursor cells are initiated to proliferate and differentiate within the first week of injury. These results demonstrate the utility of the endothelin-1 mediated subcortical stroke in the mouse to study post-stroke repair mechanisms, as the infarct core extends through the partially damaged peri-infarct white matter and induces an early glial progenitor response.","Animals;Apoptosis/physiology;Cell Proliferation;Dementia, Vascular/chemically induced/*pathology/physiopathology;Disease Models, Animal;Endothelin-1/pharmacology;Gliosis/etiology/pathology/physiopathology;Macrophages/pathology;Magnetic Resonance Imaging/methods;Male;Mice;Mice, Inbred C57BL;Myelin Sheath/pathology;Nerve Fibers, Myelinated/*pathology;Nerve Regeneration/*physiology;Neural Pathways/pathology/physiopathology;Oligodendroglia/cytology/physiology;Recovery of Function/physiology;Stem Cells/*physiology;Stroke/chemically induced/*pathology/physiopathology;Vasoconstrictor Agents/pharmacology;Wallerian Degeneration/etiology/*pathology/physiopathology","Sozmen, E. G.;Kolekar, A.;Havton, L. A.;Carmichael, S. T.",2009,Jun 15,10.1016/j.jneumeth.2009.03.017,0,
1143,Infantile-onset megalencephalic leucoencephalopathy in two siblings,"Infantile-onset megalencephalic leucoencephalopathy (IML) is a recently recognized autosomal recessive white matter disorder. Unlike other megalencephalic leucoencephalopathies, in patients with IML a mild clinical course, a slowly progressive delay in motor development and mild mental deterioration are typical. We report on two affected siblings who have typical clinical and radiological findings of IML. Cranial magnetic resonance imaging showed involvement of the capsula externa, extrema and interna, nucleus dentatus, crus cerebri, periventricular and subcortical white matter. In addition, bilateral cystic changes were determined predominantly in the temporal lobes. There were no clear biochemical or metabolic disturbances. In the present paper, we discuss the clinical and neuroimaging findings of IML.",,"Soylu, H.;Yüksel, A.;Kutlu, N. O.;Aydinli, M.;Seven, M.;Mocan, H.",2000,2000,,0,
1144,Flortaucipir F 18 Quantitation using a Parametric Estimate of Reference Signal Intensity (PERSI),"Introduction: PET imaging of tau pathology in Alzheimer's disease may benefit from the use of white matter reference regions. These regions have shown reduced variability compared to conventional cerebellar regions in amyloid imaging. However, they are susceptible to contamination from partial-volume blurring of tracer uptake in cortex. We present a new technique (PERSI) for Flortaucipir F 18 count normalization that leverages the advantages of white matter reference regions while mitigating potential partial-volume effects. Methods: Subjects with clinical diagnoses of Alzheimer's Disease (AD), mild cognitive impairment (MCI) or normal cognition (CN) underwent T1 MRI and florbetapir imaging (to determine amyloid (Abeta) status) at screening, and flortaucipir imaging at single or multiple time points. Flortaucipir images acquired as 4x5 minute frames, 80 minutes after a 370 MBq injection, were motion corrected, averaged and transformed to MNI space. The PERSI reference region was calculated for each scan by fitting a bimodal Gaussian distribution to the voxel-intensity histogram within an atlas-based white matter region, and using the center and width of the lower-intensity peak to identify the voxel intensities to be included. Four conventional reference regions were also evaluated: 1) whole cerebellum, 2) cerebellar gray matter, 3) atlas-based white matter, and 4) subject-specific white matter. SUVr was calculated for a statistically-defined neocortical volume-of-interest (MUBADA). Performance was evaluated with respect to test-retest variability in a Phase 2 study of 21 subjects (5-34 days between scans). Baseline variability in controls (SD of SUVr and DeltaSUVr values) and effect sizes for group differences (Cohen's d; Abeta+ impaired vs. Abeta- normal) were evaluated in another Phase 2 study with cross-sectional (n = 215) and longitudinal (n = 142/215; 18+/-2 months between scans) data. Results: PERSI showed superior test-retest reproducibility (1.84%) and group separation ability (cross-sectional Cohen's d=9.45; longitudinal Cohen's d=2.34) compared to other reference regions. Baseline SUVr variability and DeltaSUVr were minimal in Abeta- control subjects with no specific flortaucipir uptake (SUVr 1.0+/-0.04, DeltaSUVr 0.0+/-0.02). Conclusion: PERSI reduced variability while enhancing discrimination between diagnostic cohorts. Such improvements could lead to more accurate disease staging and robust measurements of changes in tau burden over time for the evaluation of putative therapeutic treatments.",Av1451;Flortaucipir F 18;Image Processing;Pet;Radiopharmaceuticals;SUVr;T807;reference region,"Southekal, S.;Devous, M. D., Sr.;Kennedy, I.;Navitsky, M.;Lu, M.;Joshi, A. D.;Pontecorvo, M. J.;Mintun, M. A.",2017,Nov 30,,0,
1145,Optimized feature selection technique for automatic classification of MRI images for Alzheimer's disease,"Alzheimer's disease (AD) is becoming more common among the elders globally. Physical and mental assessment were the norm to identify AD, however Magnetic Resonance Imaging (MRI) is being utilized for automatic medical analysis/interpretation. Recently, many higher dimensional classification techniques were suggested for discriminating between patients with Alzheimer's, ""Mild Cognitive Impairment (MCI)"" or normal brain automatically sing brain images obtained from MRI. For effective classification features are extracted from CerebroSpinal Fluid (CSF), White Matter (WM) and Grey Matter (GM) as well as the classifier trained. Feature extraction faces the ""curse of dimensionality"" leading to poor classifier performance. In the current study, Fish Swarm Metaheuristic is studied for effective features selection. Experiments show the effectiveness of the proposed technique.",algorithm;Alzheimer disease;article;automation;classification;classifier;feature selection;fish swarm metaheuristic;human;image analysis;image processing;measurement accuracy;neuroimaging;nuclear magnetic resonance imaging;process optimization;sensitivity and specificity;statistical parameters;support vector machine,"Sountharrajan, S.;Thangaraj, P.",2016,,10.1166/jmihi.2016.1973,0,
1146,Marchiafava-Bignami disease,"Marchiafava-Bignami disease is characterized by demyelination of the callous body. The clinical features are varied, the most frequent symptoms being: dementia, attention disorders, gait difficulty and interhemispheric deconnection syndrome. Report case: We report a 69-year-old alcoholic man who presented with mental impairment. MRI, suggestive of corpus callosum demyelination with associated white matter involvement in left cerebral hemisphere and pons. Biopsy reveled demyelination and no evidence of tumor. The diagnosis of Marchiafava-Bignami disease was confirmed. Conclusions: this case raises questions about some previous ideas on this disease, such as the prognosis of its acute forms and the significance of the extracallosal lesions seen on neuroimaging. ©INNN, 2008.",aged;alcoholism;article;attention deficit disorder;brain dysfunction;case report;clinical feature;dementia;demyelination;gait disorder;human;interhemispheric disconnection syndrome;interhemispheric transfer;male;Marchiafava Bignami disease;mental disease;nuclear magnetic resonance imaging;prognosis,"Soto, G. R.;Guerra, R. M.;Garcés, R. A.;Arcipreste, A. A.;Espinoza, I. F.;Hernández, C. D.;Sosa, A. M.",2008,,,0,
1147,Deep versus periventricular white matter lesions and cognitive function in a community sample of middle-aged participants,"The association of cerebral white matter lesions (WMLs) with cognitive status is not well understood in middle-aged individuals. Our aim was to determine the specific contribution of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) to cognitive function in a community sample of asymptomatic participants aged 50 to 65 years. One hundred stroke- and dementia-free adults completed a comprehensive neuropsychological battery and brain MRI protocol. Participants were classified according to PVH and DWMH scores (Fazekas scale). We dichotomized our sample into low grade WMLs (participants without or with mild lesions) and high grade WMLs (participants with moderate or severe lesions). Analyses were performed separately in PVH and DWMH groups. High grade DWMHs were associated with significantly lower scores in executive functioning (-0.45 standard deviations [SD]), attention (-0.42 SD), verbal fluency (-0.68 SD), visual memory (-0.52 SD), visuospatial skills (-0.79 SD), and psychomotor speed (-0.46 SD). Further analyses revealed that high grade DWMHs were also associated with a three- to fourfold increased risk of impaired scores (i.e.,<1.5 SD) in executive functioning, verbal fluency, visuospatial skills, and psychomotor speed. Our findings suggest that only DWMHs, not PVHs, are related to diminished cognitive function in middle-aged individuals. (JINS, 2012, 18, 1-12).","Aged;Cerebral Ventricles/*pathology;Cognition Disorders/diagnosis/*etiology;Depression;Executive Function;Female;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/*complications/*pathology;Magnetic Resonance Imaging;Male;Memory, Short-Term;Middle Aged;Neuropsychological Tests;Psychomotor Performance;*Residence Characteristics;Risk Factors;Statistics, Nonparametric;Stroke, Lacunar/etiology/pathology","Soriano-Raya, J. J.;Miralbell, J.;Lopez-Cancio, E.;Bargallo, N.;Arenillas, J. F.;Barrios, M.;Caceres, C.;Toran, P.;Alzamora, M.;Davalos, A.;Mataro, M.",2012,Sep,10.1017/s1355617712000677,0,
1148,The ins and outs of the BCCAo model for chronic hypoperfusion: a multimodal and longitudinal MRI approach,"Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.","Animals;Arterial Occlusive Diseases/ pathology;Basilar Artery/pathology;Behavior, Animal;Brain/blood supply/pathology/surgery;Carotid Artery, Common/ pathology;Chronic Disease;Contrast Media;Diffusion Tensor Imaging;Disease Models, Animal;Immunohistochemistry;Magnetic Resonance Imaging;Male;Multimodal Imaging;Perfusion;Rats;Rats, Wistar;Time Factors;Visual Pathways/pathology","Soria, G.;Tudela, R.;Marquez-Martin, A.;Camon, L.;Batalle, D.;Munoz-Moreno, E.;Eixarch, E.;Puig, J.;Pedraza, S.;Vila, E.;Prats-Galino, A.;Planas, A. M.",2013,,10.1371/journal.pone.0074631,0,
1149,[Localized cerebral blood flow changes in response to ADL-related vitality in elderly patients with dementia using single photon emission computed tomography],"AIM: To clarify the area in the brain related to responsible for vitality and volition. METHODS: We studied 123 outpatients (39 men, 84 women, 77.7+/-6.7 years old) who visited the Center for comprehensive care on memory disorders in Kyorin University Hospital. No patients were prescribed with anti-depressants, anti-anxiety agents, psychomimetics, acetylcholinesterase inhibitors, Chinese herbal medicines or cerebrovascular circulation modifying drugs. Patients with frontotemporal dementia or depression were excluded. ADL-related vitality and volition was measured by a vitality index. Cerebral brain blood flow was measured by single photon emission computed tomography (99mTc-ECD SPECT). Relative blood flow changes were calculated by Statistical Parametric Mapping (SPM). Absolute blood flow changes were calculated by a three-dimensional stereotaxic ROI template on anatomically standardised 99mTc-ECD SPECT (3D SRT). Statistically significant correlations between semi-quantitatively measured scores of vitality index and blood flow changes in SPM and 3D-SRT were tested and displayed on a brain map. RESULTS: Analysis of relative and absolute blood flow showed that the common responsible area in the brain related to vitality was the frontal lobe, fronto-cingulate gyrus, temporal lobe, basal ganglia (caudate nucleus) and thalamus. Blood flow changes in the orbital gyrus were strongly correlated with vitality index specially in the frontal lobe. CONCLUSION: ADL-related vitality is affected mainly by the blood flow in the frontal-subcortical circuit. However, deep white matter was also important to determine vitality and volition.","*Activities of Daily Living;Aged;Alzheimer Disease/*physiopathology;Cerebrovascular Circulation/*physiology;Female;Humans;Male;Tomography, Emission-Computed, Single-Photon;*Volition","Sonohara, K.;Toba, K.;Nakai, R.;Kobayashi, Y.;Moriya, Y.;Hasegawa, H.;Kozaki, K.;Matsuda, H.",2008,Nov,,0,
1150,Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus,"Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.",,"Sonoda, M.;Shoji, T.;Kuwamura, Y.;Okute, Y.;Naganuma, T.;Shima, H.;Motoyama, K.;Morioka, T.;Mori, K.;Fukumoto, S.;Shioi, A.;Shimono, T.;Fujii, H.;Kabata, D.;Shintani, A.;Emoto, M.;Inaba, M.",2017,Jun 29,,0,
1151,Hereditary multi-infarct dementia,"This paper summarizes the clinical and genetic features of a disease occurring in 16 patients from the same extended family, which resembles the multi-infarct dementia described by Sourander and Wȧlinder [Acta neuropath. 39: 247-254, 1977]. This family has relapsing strokes with neuropsychiatric symptoms, and they affect relatively young adult individuals of both sexes. The entity of the disease is characterized by autosomal dominant transmission with late onset and by association with occlusive cerebrovascular infarcts in the white matter, which was also generally reduced. Both of these features can be seen in the CT scan. In 13 members of this family the diagnosis can be regarded as certain and in a further 3 cases as more or less probable.",autosomal dominant inheritance;central nervous system;clinical article;computer analysis;computer assisted tomography;electroencephalogram;family;genetic disorder;human;multiinfarct dementia;cerebrovascular accident,"Sonninen, V.;Savontaus, M. L.",1987,,,0,
1152,Quantitative detection of brain aberrations in human immunodeficiency virus type 1-infected individuals by magnetic resonance imaging,"The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency.",AIDS Dementia Complex/cerebrospinal fluid/pathology;AIDS-Related Complex/cerebrospinal fluid/pathology;Adult;Aged;Biopterin/analogs & derivatives/blood;Brain/ pathology;Cerebrospinal Fluid/microbiology;Female;HIV Infections/cerebrospinal fluid/ pathology;HIV Seropositivity/cerebrospinal fluid/pathology;HIV-1/isolation & purification;Homosexuality;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neopterin;beta 2-Microglobulin/analysis,"Sonnerborg, A.;Saaf, J.;Alexius, B.;Strannegard, O.;Wahlund, L. O.;Wetterberg, L.",1990,Dec,,0,
1153,Low levels of plasma omega 3-polyunsaturated fatty acids are associated with cerebral small vessel diseases in acute ischemic stroke patients,"Cerebral small vessel diseases (SVDs) are related to stroke or cognitive dysfunction. n-3-polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) represent possible disease-modifying factors for cardiovascular disease or dementia. Our hypothesis was that a low proportion of plasma FAs would be associated with cerebral SVDs. We prospectively enrolled 220 patients with a first-episode cerebral infarction within 7 days after symptom onset. The composition of plasma FAs was analyzed by gas chromatography methods. The presence and burden of cerebral microbleeds (CMBs), high-grade white matter changes (HWCs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) were investigated. The mean proportion (+/- SD) was 2.0 +/- 0.7 for EPA, 8.9 +/- 1.5 for DHA, and 12.0 +/- 2.1 for summation operator n-3-PUFAs. In total, 46 (20.9%) patients had CMBs, 64 (29.1 %) had HWCs, 57 (25.9%) had HPVSs, and 65 (29.5%) had ALIs. In univariate analyses, CMBs, HWCs, and HPVSs were each negatively correlated with the proportion of EPA, DHA, and summation operator n-3-PUFAs. In the multivariate analysis, a lower proportion of EPA, DHA and summation operator n-3-PUFAs was associated with the presence of CMBs, HWCs and HPVS, but not ALIs. Total SVDs score was inversely correlated with the proportion of EPA, DHA and summation operator n-3-PUFAs. Overall, we found an association between low proportions of plasma n-3-PUFAs and cerebral SVDs pathologies. Further studies are needed to explore the association and potential therapeutic role of FAs in cerebral SVDs.","Aged;Aged, 80 and over;Asymptomatic Diseases;Brain Ischemia/epidemiology/*etiology;Cerebral Infarction/blood/pathology/*physiopathology;Cerebral Small Vessel Diseases/blood/pathology/*physiopathology;Cerebrovascular Circulation;Cross-Sectional Studies;*Down-Regulation;Fatty Acids, Omega-3/*blood;Female;Hospitals, University;Humans;Magnetic Resonance Imaging;Male;Microvessels/pathology;Middle Aged;Prospective Studies;Republic of Korea/epidemiology;Risk Factors;Stroke/epidemiology/*etiology;Stroke, Lacunar/epidemiology/etiology;White Matter/blood supply/pathology;Cerebral microbleeds;Fatty acids composition;Perivascular spaces;Small vessel disease;White matter changes;n-3-polyunsaturated fatty acids","Song, T. J.;Chang, Y.;Shin, M. J.;Heo, J. H.;Kim, Y. J.",2015,May,10.1016/j.nutres.2015.04.008,0,
1154,Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition,"Increasing evidence demonstrates that there is marked damage and dysfunction not only in the gray matter but also in the white matter in Alzheimer's disease (AD). In this study, transgenic mice overexpressing beta-amyloid precursor protein (APP) under control of the platelet-derived growth factor promoter (PDAPP mice) were examined using diffusion tensor magnetic resonance imaging (DTI) to evaluate the extent of white matter injury before and following the development of AD-like pathology. The profile of DTI parameters was significantly different in old PDAPP mice compared to that of old control mice following the development of AD-like pathology. No difference in DTI parameters was observed between the young PDAPP and control mice. Our results suggest that as amyloid beta (Abeta) deposition and levels increase over time in PDAPP mice, these changes lead to primary or secondary white matter injury that can be detected by DTI.","Aging;Alzheimer Disease/ pathology;Amyloid beta-Protein Precursor/genetics/ metabolism;Animals;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Disease Models, Animal;Mice;Mice, Transgenic;Plaque, Amyloid/ultrastructure;Platelet-Derived Growth Factor/genetics;Promoter Regions, Genetic","Song, S. K.;Kim, J. H.;Lin, S. J.;Brendza, R. P.;Holtzman, D. M.",2004,Apr,10.1016/j.nbd.2003.12.003,0,
1155,Cognitive profile of CADASIL patients with R544C Notch3 mutation,"BACKGROUND: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. In the present study, we aimed to analyze cognitive and neuroimaging profiles of CADASIL patients with R544C mutation. METHODS: Fifty-eight consecutive patients with R544C mutation and 26 normal controls were investigated. The patients were divided into two groups depending on the presence (CADASIL with dementia: CADASIL-D) or absence of dementia (CADASIL no dementia: CADASIL-ND). We applied the same neuropsychological test to the three groups. Brain magnetic resonance images were obtained from 58 patients with R544C mutation. Linear regression models were used to assess the impact of lacunes and white matter hyperintensities on cognitive function in the CADASIL-ND group. RESULTS: Compared to controls, the CADASIL-ND group demonstrated significant difficulties concerning measures of attention, executive function, and motor control. The CADASIL-D group was impaired in all cognitive domains that were assessed, except the language domain. After correction for age and educational level, the number of lacunes was associated with lower scores in the Alzheimer's Disease Assessment Scale cognitive subtest and Stroop color test in the CADASIL-ND group. CONCLUSIONS: Non-Caucasian CADASIL patients with R544C mutation and Caucasian CADASIL patients show similar patterns of cognitive impairment.","Age Factors;Aged;Aged, 80 and over;Asian Continental Ancestry Group/genetics;Attention;Brain/pathology;CADASIL/complications/ genetics/pathology/ psychology;Cognition;Dementia/complications/ genetics/pathology;Educational Status;Executive Function;Female;Humans;Korea;Magnetic Resonance Imaging;Male;Middle Aged;Motor Activity;Mutation;Neuropsychological Tests;Receptors, Notch/ genetics;White Matter/pathology","Song, J. K.;Noh, Y. O.;Lee, J. S.",2014,,10.1159/000356199,0,
1156,Clinical significance of silent cerebral infarctions in patients with Alzheimer disease,"BACKGROUND: Although recent advances in the epidemiology of Alzheimer disease (AD) suggest a strong association between vascular factors predisposing to cerebrovascular disease and AD, the results of many studies on the relation between cerebrovascular disease and AD have been yet controversial. Therefore, we conducted this study to clarify the relation between concomitant silent cerebral infarctions and the cognitive decline of AD patients. METHODS: One hundred and fifty subjects participated in this study: 51 patients had AD, 44 patients had AD with silent cerebral infarction (ADI), and there were 45 control subjects. These subjects received the global cognitive function testing and they were all evaluated with detailed neuropsychologic tests including attention, memory, language, and also the visuospatial and frontal function. RESULTS: Compared with the control group, the patients with AD and ADI demonstrated significantly impairments in all cognitive domains. The ADI group showed more marked impairment than did the AD group on the domains including the language function, the delayed recall test, and semantic fluency. CONCLUSIONS: ADI showed more severe cognitive decline than AD, indicating that cerebrovascular disease contributes to the severity of cognitive decline. These results suggest that prevention of cerebrovascular disease can play an important role in preventing the rapid cognitive decline of AD.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/pathology/physiopathology;Analysis of Variance;Case-Control Studies;Cerebral Infarction/complications/*pathology;Cognition Disorders/*complications/pathology;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Matched-Pair Analysis;Middle Aged;Neuropsychological Tests;Severity of Illness Index;Statistics, Nonparametric;Temporal Lobe/pathology","Song, I. U.;Kim, J. S.;Kim, Y. I.;Eah, K. Y.;Lee, K. S.",2007,Jun,10.1097/WNN.0b013e31805d859e,0,
1157,Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals,"OBJECTIVES: Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. METHODS: 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. RESULTS: At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E epsilon4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. CONCLUSIONS: Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.","Aged;Aged, 80 and over;Analysis of Variance;Apolipoproteins/*blood;Cohort Studies;Fluoroimmunoassay;Humans;Linear Models;Longitudinal Studies;Mild Cognitive Impairment/*blood;New South Wales","Song, F.;Poljak, A.;Crawford, J.;Kochan, N. A.;Wen, W.;Cameron, B.;Lux, O.;Brodaty, H.;Mather, K.;Smythe, G. A.;Sachdev, P. S.",2012,,10.1371/journal.pone.0034078,0,
1158,The effect of anemia and white matter hyperintensities (WMH) on cognitive impairment in patients with amnestic mild cognitive impairment (MCI),"Anemia and subcortical ischemic change might be associated with increased risks for cognitive impairment among the elderly. This study examined the associations among anemia, WMH and cognitive function in patients with amnestic MCI. We recruited 278 subjects with amnestic MCI from the Clinical Research Center for Dementia of South Korea (CREDOS), a hospital-based cohort study. A standardized neuropsychological battery, containing tests of language, visuospatial function, verbal memory and executive function, was used for all patients. Anemia was defined as a hemoglobin concentration below 12 g/dl for women and below 13 g/dl for men. The severity of WMH was also examined using brain magnetic resonance imaging (MRI). After multivariable adjustments, anemia and WMH were associated with poorer performance on cognitive function tests (anemia: Stroop test, F=4.17, p=0.042; WMH: Stroop test, F=6.45, p=0.002; Rey-complex figure test-copy, F=4.08, p=0.018). Moreover, a significant interaction between anemia and the severity of WMH was observed in performance on the Go/no go test (F=4.50, p=0.012) and the Stroop test (F=3.36, p=0.037). In post hoc analysis, anemic patients with severe WMH had significantly worse scores on measure of executive function (Go/no go test, p=0.011; Stroop test, p=0.001). Anemia and WMH had interactive effects on executive function impairment among the elderly with amnestic MCI.","Aged;Aged, 80 and over;Amnesia/diagnosis/ epidemiology/etiology;Anemia/complications/ epidemiology;Cohort Studies;Female;Humans;Leukoencephalopathies/complications/diagnosis/ epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/diagnosis/ epidemiology/etiology;Neuropsychological Tests;Republic of Korea/epidemiology;Severity of Illness Index","Son, S. J.;Lee, K. S.;Na, D. L.;Seo, S. W.;Kim, C. H.;Kim, J. H.;Oh, B. H.;Hong, C. H.",2012,Sep-Oct,10.1016/j.archger.2011.10.015,0,
1159,Anemia associated with depressive symptoms in mild cognitive impairment with severe white matter hyperintensities,"Depression with mild cognitive impairment (MCI) may be associated with a high risk of dementia. Likewise, anemia and subcortical ischemic changes might be associated with depression in the elderly individuals. We examined the relationship between anemia, subcortical ischemic changes, and depressive symptoms in 388 elderly patients with MCI (74.0% women, mean age = 71.8) who were evaluated at the Clinical Research Center for Dementia of South Korea. Blood samples were drawn from all consenting participants and depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). We also evaluated the severity of white matter hyperintensities (WMH) on brain using magnetic resonance imaging (MRI). After a multivariable adjustment, we found no significant differences in GDS-15 score between anemic and nonanemic groups (F = 3.0, P = .085) and among WMH level groups (F = 0.6, P = .574) independently. However, the interaction between anemia and the severity of WMH was significantly associated with depressive symptoms (analysis of covariance, F = 7.8, P < .001). In post hoc tests, a higher depressive symptom score was observed in anemic participants with severe WMH. Anemia with severe subcortical ischemic changes appears to be related to depressive symptoms in patients with MCI.","Aged;Aged, 80 and over;Anemia/ complications/pathology;Brain/ pathology;Depression/ complications/diagnosis/pathology;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ complications/pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Psychiatric Status Rating Scales;Risk Factors","Son, S. J.;Lee, K. S.;Na, D. L.;Seo, S. W.;Kim, C. H.;Kim, J. H.;Oh, B. H.;Hong, C. H.",2011,Sep,10.1177/0891988711417132,0,
1160,Association between white matter hyperintensity severity and cognitive impairment according to the presence of the apolipoprotein E (APOE) epsilon4 allele in the elderly: retrospective analysis of data from the CREDOS study,"OBJECTIVE: To investigate the effect of white matter hyperintensity (WMH) severity on cognitive function according to presence of the apolipoprotein E (APOE) epsilon4 allele. METHOD: From participants in a nationwide, multicenter, hospital-based cohort study of dementia by the Clinical Research Center for Dementia of South Korea (November 2005 to December 2011), data for 5,077 elderly subjects (mean [SD] age = 71.37 [8.40] years) who had available data for APOE genotype and WMH severity were studied retrospectively. We used the diagnostic criteria for mild cognitive impairment proposed by Petersen et al; the diagnostic criteria for vascular dementia included in DSM-IV; and, for probable Alzheimer's disease, the criteria issued by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. WMH severity was evaluated using modified criteria of Fazekas et al and Scheltens et al using T2 axial or fluid-attenuated inversion recovery magnetic resonance images, yielding 3 groups for WMH severity level. APOE genotype was determined by analysis of venous blood, and all participants were classified into 2 groups depending on presence or absence of the APOE epsilon4 allele. The Seoul Neuropsychological Screening Battery-Dementia Version was used for all subjects. Cognitive impairment, classified by 6 cognitive test scores, was the primary outcome measure. Using multiple logistic regression, we investigated which cognitive domains were associated with WMH severity and the APOE epsilon4 allele, and, using analysis of covariance, we examined the interaction effects of these 2 factors on cognitive test scores. RESULTS: After multivariable adjustments, logistic regression analyses showed that WMH severity was associated with higher odds of cognitive impairment on frontal/executive function tests in both APOE epsilon4 carriers (odds ratio [OR] = 2.49; 95% CI, 1.65-3.76) and noncarriers (OR = 2.36; 95% CI, 1.83-3.03). WMH severity was not significantly associated with memory function in APOE epsilon4 carriers: for verbal memory, epsilon4 noncarriers had an OR of 1.44 (95% CI, 1.13-1.84), and epsilon4 carriers had an OR of 1.36 (95% CI, 0.87-2.04); for visuospatial memory, epsilon4 noncarriers had an OR of 1.86 (95% CI, 1.45-2.37), and epsilon4 carriers had an OR of 1.35 (95% CI, 0.89-2.04). Moreover, a significant interaction effect between APOE epsilon4 and WMH severity was confirmed on memory tests by analysis of covariance (verbal memory: F = 3.40, P = .033; visuospatial memory: F = 8.49, P < .001). CONCLUSIONS: Severe WMHs appear to be predominantly associated with frontal/executive dysfunction, irrespective of APOE epsilon4 allele presence. WMH severity and APOE epsilon4 had an interactive effect on memory function, with WMH severity affecting memory impairment only in APOE epsilon4 noncarriers.","Aged;Aged, 80 and over;Alleles;Alzheimer Disease/ diagnosis/ genetics;Apolipoprotein E4/ genetics;Brain/ pathology;Cerebral Ventricles/pathology;Dementia, Vascular/ diagnosis/ genetics;Female;Heterozygote Detection;Humans;Image Interpretation, Computer-Assisted;Leukoencephalopathies/ diagnosis/ genetics;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ genetics;Multivariate Analysis;Neuropsychological Tests/ statistics & numerical data;Psychometrics;Retrospective Studies","Son, S. J.;Lee, K. S.;Lee, Y.;Baek, J. H.;Choi, S. H.;Na, D. L.;Seo, S. W.;Oh, B. H.;Hong, C. H.",2012,Dec,10.4088/JCP.12m07702,0,
1161,Cerebral white matter lesions after pre-eclampsia,"BACKGROUND: Women who have had pre-eclampsia in their previous pregnancies demonstrate a greater prevalence of cerebral white matter lesions several years after the pregnancy than women who have been normotensive during their pregnancy. Both the pathophysiology and the timing of development of these lesions are uncertain. White matter lesions, in the general population, are associated with an increased risk of stroke, dementia and death. AIMS AND OBJECTIVES: The objective of the study was to determine the prevalence of cerebral white matter lesions amongst women with severe pre-eclampsia at delivery, 6months and 1year postpartum and to establish the possible pathophysiology and risks factors. METHODS: This was a longitudinal study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria South Africa. Ninety-four women with severe pre-eclampsia were identified and recruited during the delivery admission. Magnetic resonance imaging (MRI) of the brain was performed post - delivery and at 6months and 1year postpartum. RESULTS: Cerebral white matter lesions were demonstrated in 61.7% of women at delivery, 56.4% at 6months and 47.9% at 1year. Majority of the lesions were found in the frontal lobes of the brain. The presence of lesions at 1year post-delivery was associated with the number of drugs needed to control blood pressure during pregnancy (OR 5.1, 95% CI 2.3-11.3, p<0.001). The prevalence of WMLs at 1year was double in women with chronic hypertension at 1year compared to those women who were normotensive (65.1% vs 32.3%). CONCLUSION: Women who require 2 or more drugs to control blood pressure during pregnancy have an increased risk of developing cerebral white matter lesions after delivery.",,"Soma-Pillay, P.;Suleman, F. E.;Makin, J. D.;Pattinson, R. C.",2017,Apr,,0,1162
1162,Cerebral white matter lesions after pre-eclampsia,"Background: Women who have had pre-eclampsia in their previous pregnancies demonstrate a greater prevalence of cerebral white matter lesions several years after the pregnancy than women who have been normotensive during their pregnancy. Both the pathophysiology and the timing of development of these lesions are uncertain. White matter lesions, in the general population, are associated with an increased risk of stroke, dementia and death. Aims and objectives: The objective of the study was to determine the prevalence of cerebral white matter lesions amongst women with severe pre-eclampsia at delivery, 6. months and 1. year postpartum and to establish the possible pathophysiology and risks factors. Methods: This was a longitudinal study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria South Africa. Ninety-four women with severe pre-eclampsia were identified and recruited during the delivery admission. Magnetic resonance imaging (MRI) of the brain was performed post - delivery and at 6. months and 1. year postpartum. Results: Cerebral white matter lesions were demonstrated in 61.7% of women at delivery, 56.4% at 6. months and 47.9% at 1. year. Majority of the lesions were found in the frontal lobes of the brain. The presence of lesions at 1. year post-delivery was associated with the number of drugs needed to control blood pressure during pregnancy (OR 5.1, 95% CI 2.3-11.3, p. <. 0.001). The prevalence of WMLs at 1. year was double in women with chronic hypertension at 1. year compared to those women who were normotensive (65.1% vs 32.3%). Conclusion: Women who require 2 or more drugs to control blood pressure during pregnancy have an increased risk of developing cerebral white matter lesions after delivery.",antihypertensive therapy;controlled study;female;frontal lobe;human;hypertension;longitudinal study;major clinical study;male;nuclear magnetic resonance imaging;obstetric delivery;preeclampsia;pregnancy;prevalence;South Africa;tertiary care center;white matter,"Soma-Pillay, P.;Suleman, F. E.;Makin, J. D.;Pattinson, R. C.",2017,,10.1016/j.preghy.2017.02.001,0,
1163,Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease,"OBJECTIVES: Cholesterol has been linked to Alzheimer's disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and 27-hydroxycholesterol) with brain volumes in memory clinic patients. METHODS: 96 patients (33 with subjective cognitive impairment--SCI; 36 with mild cognitive impairment--MCI; 27 with AD) referred to the Memory Clinic at Karolinska University Hospital, Sweden. Plasma assessments were done by isotope dilution-mass spectrometry. MRI measurements were done using custom-made software BMAP (imaging laboratory, Karolinska Institutet), running on HERMES platform. RESULTS: Ratios of 24-hydroxycholesterol, 27-hydroxycholesterol, lanosterol and lathosterol to cholesterol (R_24OHC, R_27OHC, R_lanosterol and R_lathosterol) were significantly lower in patients with AD. In the whole population, after controlling for age, sex, APOE genotype and statins, R_24OHC was positively related to gray matter (GM) fraction. However, when groups were considered separately, the relation to GM volume, GM and parenchymal fractions was significant in the SCI group only (p<0.05). There was a significant positive association between cholesterol and white matter (WM) volume, WM and parenchymal fractions in patients with AD. CONCLUSIONS: Plasma R_24OHC was lower in patients with AD, but R_24OHC was significantly related to brain volumes in the control group only. One reason may be the previously demonstrated abnormal expression of cholesterol 24S-hydroxylase in astrocytes in AD, which may limit the usefulness of this plasma marker in this specific disease. The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis.","Age Factors;Aged;Alzheimer Disease/ blood/genetics/ pathology;Apolipoproteins E/genetics;Brain/ pathology;Cholesterol/blood;Cholesterol, HDL/blood;Cholesterol, LDL/blood;Cognition Disorders/ blood/genetics/ pathology;Female;Genotype;Humans;Hydroxycholesterols/ blood;Lanosterol/blood;Male;Middle Aged;Organ Size;Sex Factors","Solomon, A.;Leoni, V.;Kivipelto, M.;Besga, A.;Oksengard, A. R.;Julin, P.;Svensson, L.;Wahlund, L. O.;Andreasen, N.;Winblad, B.;Soininen, H.;Bjorkhem, I.",2009,Oct 2,10.1016/j.neulet.2009.06.073,0,
1164,In vivo parahippocampal white matter pathology as a biomarker of disease progression to Alzheimer's disease,"Noninvasive diagnostic tests for Alzheimer's disease (AD) are limited. Postmortem diagnosis is based on density and distribution of neurofibrillary tangles (NFTs) and amyloid-rich neuritic plaques. In preclinical stages of AD, the cells of origin for the perforant pathway within the entorhinal cortex are among the first to display NFTs, indicating its compromise in early stages of AD. We used diffusion tensor imaging (DTI) to assess the integrity of the parahippocampal white matter in mild cognitive impairment (MCI) and AD, as a first step in developing a noninvasive tool for early diagnosis. Subjects with AD (N = 9), MCI (N = 8), or no cognitive impairment (NCI; N = 20) underwent DTI-MRI. Fractional anisotropy (FA) and mean (MD) and radial (RD) diffusivity measured from the parahippocampal white matter in AD and NCI subjects differed greatly. Discriminant analysis in the MCI cases assigned statistical membership of 38% of MCI subjects to the AD group. Preliminary data 1 year later showed that all MCI cases assigned to the AD group either met the diagnostic criteria for probable AD or showed significant cognitive decline. Voxelwise analysis in the parahippocampal white matter revealed a progressive change in the DTI patterns in MCI and AD subjects: whereas converted MCI cases showed structural changes restricted to the anterior portions of this region, in AD the pathology was generalized along the entire anterior-posterior axis. The use of DTI for in vivo assessment of the parahippocampal white matter may be useful for identifying individuals with MCI at highest risk for conversion to AD and for assessing disease progression.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Diffusion Magnetic Resonance Imaging;Disease Progression;Female;Humans;Image Interpretation, Computer-Assisted;Male;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology;Parahippocampal Gyrus/ pathology","Solodkin, A.;Chen, E. E.;Van Hoesen, G. W.;Heimer, L.;Shereen, A.;Kruggel, F.;Mastrianni, J.",2013,Dec 15,10.1002/cne.23418,0,
1165,"Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy","A 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy and was followed for 4 years after bone marrow transplantation (BMT). MRI, neurophysiological tests (EEG, ENeG, VEP, SEP and BAEP) and neuropsychological assessment were performed before, and repeatedly after BMT. MRI showed symmetrical white matter lesions in the frontal and parieto-occipital lobes and in the corpus callosum, EEG showed frontal and temporal slow wave abnormalities and nerve conduction was slow. Neuropsychological tests showed cognitive impairment in executive functions, decline in visuospatial-constructive and spatial memory tasks and disorganized thinking, IQ was low (52), with slightly better values for verbal IQ than for performance IQ. After BMT, the patient was followed for 4 years. Clear improvements were seen in EEG, in peripheral nerve conduction and in neuropsychological tests (especially in verbal IQ). MRI findings were unchanged. We believe that the improvement in our patient resulted from the bone marrow transplantation.",adult;article;bone marrow transplantation;case report;cognitive defect;corpus callosum;electroencephalogram;female;frontal lobe;human;intelligence quotient;metachromatic leukodystrophy;nerve conduction;neurophysiology;neuropsychological test;occipital lobe;parietal lobe;peripheral nervous system;priority journal;slow brain wave;spatial memory;white matter,"Solders, G.;Celsing, G.;Hagenfeldt, L.;Ljungman, P.;Isberg, B.;Ringdén, O.",1998,,,0,
1166,Agreement in the clinical diagnosis of dementia: Evaluation of a case series with mild cognitive impairment,"Interobserver agreement in the clinical diagnosis of dementia among four neurologists was evaluated. The physicians, masked to the original diagnoses, independently reviewed the clinical records of 50 outpatients consulting either the 1st University Neurology Department of Milan or the Neuropsychology Unit of the Medical Center of Veruno (Novara) for suspected cognitive impairment, during a 6-month period. The records contained patients' medical and neurological history, results of neuropsychological testing, laboratory tests, cerebral computed tomography and other investigations. For each patient, the raters had to provide both a diagnosis concerning the presence or absence of dementia and to assign an analytical diagnosis to all the dementia cases. The κ statistic was used as a measure of interrater reliability. The level of agreement on the primary diagnosis of dementia was moderate (κ = 0.49); with respect to the nosological diagnoses, the κ values ranged from 0.16 for depression to 0.80 for multi-infarct dementia.",adult;aged;article;cognitive defect;controlled study;dementia;female;human;major clinical study;male,"Solari, A.;Cossa, F. M.;Denes, F.;Gainotti, G.;Grossi, D.;Nichelli, P.;Filippini, G.",1994,,,0,
1167,Stroke and multi-infarct dementia as presenting symptoms of giant cell arteritis: Report of 7 cases and review of the literature,"Cerebrovascular accidents (CVAs) and multi-infarct dementia have rarely been reported as presenting symptoms of giant cell arteritis (GCA), although 3%-4% of patients with GCA may present with CVAs during the course of the disease. We describe 7 patients with biopsy-proven GCA who presented with stroke or multi-infarct dementia. Most of them had other symptoms of GCA when the disease began that were misdiagnosed or not noticed. The internal carotid arteries were involved in 4 patients and the vertebrobasilar arteries in 3, with bilateral vertebral artery occlusion in 1. Small cerebral infarction foci on cranial computed tomography (CT) scan and magnetic resonance imaging (MRI) were found in 5 cases, and cerebellar infarction, in 2. MR angiography showed intracranial arteritis in 4 cases. Treatment with glucocorticoids and adjunctive antiplatelet or anticoagulant therapy was given in all cases, with neurologic improvement in 5. Two patients died. Necropsy demonstrated generalized GCA involving the medium and small cerebral vessels in 1 case.Central nervous system involvement is a rare complication in GCA but is important to recognize, as it can be reversible if diagnosed and treated promptly. Suspicion should arise in elderly patients suffering from strokes with a quickly progressing stepwise course and associated headache, fever, or inflammatory syndrome. In these cases, temporal artery biopsy should be performed without delay. Early diagnosis of GCA and immediate initiation of corticosteroid treatment may prevent progressive deterioration and death. Additional antiplatelet or anticoagulant therapy should be evaluated according to the individual risk and benefit to the patient under care. Copyright © 2008 by Lippincott Williams & Wilkins.",,"Solans-Laqué, R.;Bosch-Gil, J. A.;Molina-Catenario, C. A.;Ortega-Aznar, A.;Alvarez-Sabin, J.;Vilardell-Tarres, M.",2008,November,,0,
1168,Computed tomography findings in senile dementia and normal aging,"Computed tomography (CT) findings in 57 patients with senile dementia of Alzheimer type (SDAT), 19 patients with multi-infarct dementia and 85 controls of similar age and sex were studied. The SDAT patients differed from the controls of ventricular dilatation, frontal horn index, cella media index and the width of the third ventricle, and also in the index of cortical atrophy. Even the least severely demented SDAT patients differed from the controls. In the SDAT group with the increasing degree of intellectual impairment the ventricular dilatation increased, but cortical atrophy did not correlate with the psychological test score. The multi-infarct dementia patients differed from the controls in all CT variables including local changes. The SDAT patients had a more marked ventricular dilatation than the multi-infarct dementia patients. The multi-infarct dementia patients had more frequently local changes in SDAT patients. In the control group age correlated with ventricular dilatation, and the lower test scores correlated with cortical atrophy in the left temporal region.","Aged;Alzheimer Disease/*radiography;Brain/*radiography;Dementia/*radiography;Female;Humans;Intelligence;Male;Psychological Tests;Reference Values;Tomography, X-Ray Computed","Soininen, H.;Puranen, M.;Riekkinen, P. J.",1982,Jan,,0,
1169,A case of pigmentary orthochromatic leukodystrophy with findings of proton MR spectroscopy and serial brain MRIs,"Despite a few case reports over the last 60 years, little progress has been made in defining the phenotype, genotype and pathophysiological mechanisms involved in pigmentary orthochromatic leukodystrophy (POLD). Furthermore, there is currently no data available regarding MRI in patients in the relatively early stages of POLD. Here, we present a 37 year old male patient with brain biopsy-proven POLD who had brain MRIs three times during the first year of his clinical course and proton MR spectroscopy (MRS) throughout his diagnostic evaluation. This patient with POLD was clinically characterized by seizures, rapidly progressive frontally predominant dementia and gait disturbance. The brain MRIs taken serially over the first year revealed progressive development of frontal-predominant white matter changes in the periventricular areas during the earlier periods, which later spread into the deep white matter. His MRS was helpful in the diagnostic approach because the results enabled demyelinating changes to be distinguished from other disease processes such as ischemia, gliosis or tumors. The MRS findings also reflected the disease dynamics because metabolic derangement was observed, even in the white matter that appeared normal. The findings presented here provide insight into the dynamics of POLD. © 2010 Elsevier B.V. All rights reserved.",alpha tocopherol;amino acid;antinuclear antibody;cerebroside sulfatase;cholesterol;cyanocobalamin;electrolyte;folic acid;lipofuscin;long chain fatty acid;neutrophil cytoplasmic antibody;triacylglycerol;adult;agricultural worker;article;behavior disorder;blood cell count;blood sampling;brain biopsy;brain ischemia;brain tumor;case report;cerebrospinal fluid culture;cognitive defect;diagnostic imaging;differential diagnosis;disease course;electrolyte blood level;erythrocyte sedimentation rate;frontotemporal dementia;gait disorder;glia cell;gliosis;human;Human immunodeficiency virus;human tissue;leukodystrophy;liver function test;macrophage;male;Mini Mental State Examination;nerve conduction;neuroimaging;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;parkinsonism;pigmentary orthochromatic leukodystrophy;priority journal;proton nuclear magnetic resonance;psychomotor disorder;serology;stereotactic biopsy;syphilis;thyroid function test;tonic clonic seizure;white matter,"Sohn, S. Y.;Ko, Y. J.;Hong, J. M.;Kim, S. H.;Kim, H. S.;Kim, J. H.;Chi, J. G.;Moon, S. Y.",2010,,,0,
1170,"Comparison of regional gray matter atrophy, white matter alteration, and glucose metabolism as a predictor of the conversion to Alzheimer's disease in mild cognitive impairment","We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimer's disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period.",Aged;Alzheimer Disease/complications/ diagnosis;Atrophy/pathology;Biomarkers/blood;Brain/ pathology;Diffusion Tensor Imaging/methods;Female;Glucose/ metabolism;Gray Matter/ pathology;Humans;Male;Mild Cognitive Impairment/ diagnosis/etiology;Neuroimaging/methods;Positron-Emission Tomography/methods;Reproducibility of Results;Sensitivity and Specificity;Severity of Illness Index;White Matter/ pathology,"Sohn, B. K.;Yi, D.;Seo, E. H.;Choe, Y. M.;Kim, J. W.;Kim, S. G.;Choi, H. J.;Byun, M. S.;Jhoo, J. H.;Woo, J. I.;Lee, D. Y.",2015,Jun,10.3346/jkms.2015.30.6.779,0,
1171,White matter hyperintensities and the course of depressive symptoms in elderly people with mild dementia,"OBJECTIVES: To explore the relationship between white matter hyperintensities (WMH) and the prevalence and course of depressive symptoms in mild Alzheimer's disease (AD) and Lewy body dementia. DESIGN: This is a prospective cohort study conducted in secondary care outpatient clinics in western Norway. SUBJECTS: The study population consisted of 77 elderly people with mild dementia diagnosed according to standardised criteria. METHODS: Structured clinical interviews and physical, neurological, psychiatric, and neuropsychological examinations were performed and routine blood tests were taken. Depression was assessed using the depression subitem of the Neuropsychiatric Inventory and the Montgomery-Asberg Depression Rating Scale (MADRS). A standardised protocol for magnetic resonance imaging scan was used, and the volumes of WMH were quantified using an automated method, followed by manual editing. RESULTS: The volumes of total and frontal deep WMH were significantly and positively correlated with baseline severity of depressive symptoms, and depressed patients had significantly higher volumes of total and frontal deep WMH than non-depressed patients. Higher volumes of WMH were also associated with having a high MADRS score and incident and persistent depression at follow-up. After adjustment for potential confounders, frontal deep WMH, in addition to prior depression and non-AD dementia, were still significantly associated with baseline depressive symptoms (p = 0.015, OR 3.703, 95% CI 1.294-10.593). Similar results emerged for total WMH. CONCLUSION: In elderly people with mild dementia, volumes of WMH, in particular frontal deep WMH, were positively correlated with baseline severity of depressive symptoms, and seemed to be associated with persistent and incident depression at follow-up. Further studies of the mechanisms that determine the course of depression in mild dementia are needed.",,"Soennesyn, H.;Oppedal, K.;Greve, O. J.;Fritze, F.;Auestad, B. H.;Nore, S. P.;Beyer, M. K.;Aarsland, D.",2012,Jan,000335497,0,
1172,Relationship between orthostatic hypotension and white matter hyperintensity load in older patients with mild dementia,"BACKGROUND/OBJECTIVES: White matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans of the brain, and orthostatic hypotension (OH) are both common in older people. We tested the hypothesis that OH is associated with WMH. DESIGN: Cross-sectional study. SETTING: Secondary care outpatient clinics in geriatric medicine and old age psychiatry in western Norway. PARTICIPANTS: 160 older patients with mild dementia, diagnosed according to standardised criteria. MEASUREMENTS: OH was diagnosed according to the consensus definition, measuring blood pressure (BP) in the supine position and within 3 minutes in the standing position. MRI scans were performed according to a common protocol at three centres, and the volumes of WMH were quantified using an automated method (n=82), followed by manual editing. WMH were also quantified using the visual Scheltens scale (n=139). Multiple logistic regression analyses were applied, with highest vs. lowest WMH quartile as response. RESULTS: There were no significant correlations between WMH volumes and systolic or diastolic orthostatic BP drops, and no significant correlations between Scheltens scores of WMH and systolic or diastolic BP drops. In the multivariate analyses, only APOEepsilon4 status remained a significant predictor for WMH using the automated method (p=0.037, OR 0.075 (0.007-0.851)), whereas only age remained a significant predictor for WMH scores (p=0.019, OR 1.119 (1.018-1.230)). CONCLUSION: We found no association between OH and WMH load in a sample of older patients with mild dementia.","Aged;Aged, 80 and over;Brain/ physiopathology;Cross-Sectional Studies;Dementia/ physiopathology;Female;Humans;Hypotension, Orthostatic/ physiopathology;Magnetic Resonance Imaging;Male","Soennesyn, H.;Nilsen, D. W.;Oppedal, K.;Greve, O. J.;Beyer, M. K.;Aarsland, D.",2012,,10.1371/journal.pone.0052196,0,
1173,Cerebral changes on MRI and cognitive function: the CASCADE study,"The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4+/-3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies.","Age Distribution;Aged;Brain/ pathology;Cognition Disorders/ diagnosis;Cohort Studies;Europe/epidemiology;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ statistics & numerical data;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Prevalence;Reproducibility of Results;Risk Assessment/ methods;Risk Factors;Sensitivity and Specificity;Sex Distribution;Social Class","Soderlund, H.;Nilsson, L. G.;Berger, K.;Breteler, M. M.;Dufouil, C.;Fuhrer, R.;Giampaoli, S.;Hofman, A.;Pajak, A.;de Ridder, M.;Sans, S.;Schmidt, R.;Launer, L. J.",2006,Jan,10.1016/j.neurobiolaging.2004.12.008,0,
1174,Pharmacokinetics of (1)(8)F flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer's disease,"PURPOSE: The aim of this study was to investigate the potential of [(18)F]flutemetamol as a preclinical PET tracer for imaging beta-amyloid (Abeta) deposition by comparing its pharmacokinetics to those of [(11)C]Pittsburgh compound B ([(11)C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [(18)F]flutemetamol to Abeta deposits was studied in the Tg2576 transgenic mouse model of Alzheimer's disease. METHODS: [(18)F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [(11)C]PIB and [(18)F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [(18)F]flutemetamol to Abeta deposits was also studied using ex vivo and in vitro autoradiography. The location of Abeta deposits in the brain was determined with thioflavine S staining and immunohistochemistry. RESULTS: The pharmacokinetics of [(18)F]flutemetamol resembled that of [(11)C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [(18)F]flutemetamol into radioactive metabolites was faster than that of [(11)C]PIB. [(18)F]Flutemetamol cleared more slowly from the brain than [(11)C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [(11)C]PIB and [(18)F]flutemetamol were 2.28 and 6.65 muSv/MBq, respectively. Autoradiographs showed [(18)F]flutemetamol binding to fibrillar Abeta deposits in the brain of Tg2576 mice. CONCLUSION: Based on its pharmacokinetic profile, [(18)F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to Abeta deposits in the brain of Tg2576 mice. However, its high lipophilicity might complicate the analysis of PET data, particularly in small-animal imaging.","Alzheimer Disease/genetics/ radionuclide imaging;Amyloid beta-Peptides/ metabolism;Aniline Compounds/ pharmacokinetics;Animals;Benzothiazoles/ pharmacokinetics;Disease Models, Animal;Fluorine Radioisotopes/pharmacokinetics;Mice;Mice, Inbred C57BL;Mice, Transgenic;Positron-Emission Tomography;Radiopharmaceuticals/ pharmacokinetics;Rats;Rats, Sprague-Dawley;Thiazoles/pharmacokinetics;Tissue Distribution","Snellman, A.;Rokka, J.;Lopez-Picon, F. R.;Eskola, O.;Wilson, I.;Farrar, G.;Scheinin, M.;Solin, O.;Rinne, J. O.;Haaparanta-Solin, M.",2012,Nov,10.1007/s00259-012-2178-9,0,
1175,Reduced medial temporal lobe functionality in stroke patients: a functional magnetic resonance imaging study,"Stroke is a leading cause of disability, not only because of motor limitations, but also because of the frequent occurrence of post-stroke cognitive impairment. This is illustrated by the fact that the risk of post-stroke dementia is reportedly higher than a recurrent stroke. The loss of subcortical and cortical functions in the post-stroke cognitive dysfunction spectrum is usually well explained by the size and location of the infarction. However, this does not apply for post-stroke memory dysfunction (especially episodic memory dysfunction), as there is almost never an infarction in the medial temporal lobe. Involvement of the medial temporal lobe in post-stroke memory dysfunction seems likely since this structure is essential for memory encoding and retrieval. For a proper episodic memory function, the medial temporal lobe depends on intact connections with virtually the whole brain. Disconnection from other brain areas due to the infarction could lead to a reduced medial temporal lobe function and the attendant reduced episodic memory function. We investigated medial temporal lobe functionality in 28 'first-ever' stroke patients and 22 healthy controls with the aid of functional magnetic resonance imaging. Stroke patients with a reduced episodic memory function 6-8 weeks after infarction had reduced medial temporal lobe functionality. Post-stroke reduced medial temporal lobe functionality may be responsible for the frequent observation of impaired post-stroke episodic memory function. Insight into this mechanism could be helpful in identifying which stroke patients may be at increased risk for developing post-stroke dementia and those who could benefit from early cognitive rehabilitation. The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain.",,"Snaphaan, L.;Rijpkema, M.;Van Uden, I.;Fernández, G.;De Leeuw, F. E.",2009,July,,0,
1176,White matter tracts of speech and language,"Diffusion tensor imaging (DTI) has been used to investigate the white matter (WM) tracts underlying the perisylvian cortical regions known to be associated with language function. The arcuate fasciculus is composed of 3 segments (1 long and 2 short) whose separate functions correlate with traditional models of conductive and transcortical motor or sensory aphasia, respectively. DTI mapping of language fibers is useful in presurgical planning for patients with dominant hemisphere tumors, particularly when combined with functional magnetic resonance imaging. DTI has found damage to language networks in stroke patients and has the potential to influence poststroke rehabilitation and treatment. Assessment of the WM tracts involved in the default mode network has been found to correlate with mild cognitive impairment, potentially explaining language deficits in patients with apparently mild small vessel ischemic disease. Different patterns of involvement of language-related WM structures appear to correlate with different clinical subtypes of primary progressive aphasias.",,"Smits, M.;Jiskoot, L. C.;Papma, J. M.",2014,1,,0,
1177,Leuko-araiosis: description and clinical correlates,"The term leuko-araiosis as predicted by Hachinski may now have outlived its usefulness. Careful delineation of the white matter changes seen in MR imaging by use of the MR characteristics and by the location of the lesions may reduce the apparent heterogeneity of the associate clinical and neuropathological findings. As currently defined, leuko-araiosis is seen in aggregate more commonly in subjects with cerebro-vascular disease or with cerebro-vascular risk factors but it is a common finding associated with aging in otherwise normal, healthy elderly subjects. Its clinical significance as an isolated finding in these populations should therefore be treated cautiously. Its appearance should alert the physician however to seek for and treat potential cerebro-vascular risk factors.","Alzheimer Disease/ diagnosis/pathology/radiography;Brain/ pathology/radiography;Cerebral Ventricles/anatomy & histology/pathology;Dementia, Multi-Infarct/diagnosis/pathology/radiography;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Prospective Studies;Terminology as Topic;Tomography, X-Ray Computed","Smith, R. R.;Hendrie, H. C.",1992,Jan,,0,
1178,Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease,"We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer's disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-epsilon4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories.",,"Smith, J. C.;Nielson, K. A.;Woodard, J. L.;Seidenberg, M.;Durgerian, S.;Hazlett, K. E.;Figueroa, C. M.;Kandah, C. C.;Kay, C. D.;Matthews, M. A.;Rao, S. M.",2014,,10.3389/fnagi.2014.00061,0,
1179,Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders,"Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.",aged;Alzheimer disease;APOE epsilon 4 gene;article;controlled study;daily life activity;diffusion tensor imaging;disease association;episodic memory;female;fractional anisotropy;gene;genetic risk;high risk patient;human;leisure;low risk patient;major clinical study;male;neuropathology;priority journal;white matter,"Smith, J. C.;Lancaster, M. A.;Nielson, K. A.;Woodard, J. L.;Seidenberg, M.;Durgerian, S.;Sakaie, K.;Rao, S. M.",2016,,,0,
1180,Interactive effects of physical activity and APOE-epsilon4 on white matter tract diffusivity in healthy elders,"Older adult apolipoprotein-E epsilon 4 (APOE-epsilon4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-epsilon4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18months compared to sedentary epsilon4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-epsilon4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-epsilon4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-epsilon4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-epsilon4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-epsilon4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.",,"Smith, J. C.;Lancaster, M. A.;Nielson, K. A.;Woodard, J. L.;Seidenberg, M.;Durgerian, S.;Sakaie, K.;Rao, S. M.",2016,May 1,10.1016/j.neuroimage.2015.08.007,0,
1181,Complexity in the genetic architecture of leukoaraiosis in hypertensive sibships from the GENOA Study,"BACKGROUND: Subcortical white matter hyperintensity on magnetic resonance imaging (MRI) of the brain, referred to as leukoaraiosis, is associated with increased risk of stroke and dementia. Hypertension may contribute to leukoaraiosis by accelerating the process of arteriosclerosis involving penetrating small arteries and arterioles in the brain. Leukoaraiosis volume is highly heritable but shows significant inter-individual variability that is not predicted well by any clinical covariates (except for age) or by single SNPs. METHODS: As part of the Genetics of Microangiopathic Brain Injury (GMBI) Study, 777 individuals (74% hypertensive) underwent brain MRI and were genotyped for 1649 SNPs from genes known or hypothesized to be involved in arteriosclerosis and related pathways. We examined SNP main effects, epistatic (gene-gene) interactions, and context-dependent (gene-environment) interactions between these SNPs and covariates (including conventional and novel risk factors for arteriosclerosis) for association with leukoaraiosis volume. Three methods were used to reduce the chance of false positive associations: 1) false discovery rate (FDR) adjustment for multiple testing, 2) an internal replication design, and 3) a ten-iteration four-fold cross-validation scheme. RESULTS: Four SNP main effects (in F3, KITLG, CAPN10, and MMP2), 12 SNP-covariate interactions (including interactions between KITLG and homocysteine, and between TGFB3 and both physical activity and C-reactive protein), and 173 SNP-SNP interactions were significant, replicated, and cross-validated. While a model containing the top single SNPs with main effects predicted only 3.72% of variation in leukoaraiosis in independent test samples, a multiple variable model that included the four most highly predictive SNP-SNP and SNP-covariate interactions predicted 11.83%. CONCLUSION: These results indicate that the genetic architecture of leukoaraiosis is complex, yet predictive, when the contributions of SNP main effects are considered in combination with effects of SNP interactions with other genes and covariates.",,"Smith, J. A.;Turner, S. T.;Sun, Y. V.;Fornage, M.;Kelly, R. J.;Mosley, T. H.;Jack, C. R.;Kullo, I. J.;Kardia, S. L.",2009,,10.1186/1755-8794-2-16,0,
1182,The functional neuroanatomy of geriatric depression,"OBJECTIVE: Positron Emission Tomography (PET) studies of cerebral glucose metabolism have demonstrated sensitivity in evaluating the functional neuroanatomy of treatment response variability in depression, as well as in the early detection of functional changes associated with incipient cognitive decline. The evaluation of cerebral glucose metabolism in late life depression may have implications for understanding treatment response variability, as well as evaluating the neurobiological basis of depression in late life as a risk factor for dementia. METHODS: Sixteen patients with geriatric depression and 13 comparison subjects underwent resting PET studies of cerebral glucose metabolism, as well as magnetic resonance (MR) imaging scans to evaluate brain structure. RESULTS: Cerebral glucose metabolism was elevated in geriatric depressed patients relative to comparison subjects in anterior (right and left superior frontal gyrus) and posterior (precuneus, inferior parietal lobule) cortical regions. Cerebral atrophy (increased cerebrospinal fluid [CSF] and decreased grey and white matter volumes) were observed in some of these regions, as well. Regional cerebral metabolism was positively correlated with severity of depression and anxiety symptoms. CONCLUSIONS: In contrast to decreased metabolism observed in normal aging and neurodegenerative conditions such as Alzheimer's disease, cortical glucose metabolism was increased in geriatric depressed patients relative to demographically matched controls, particularly in brain regions in which cerebral atrophy was observed, which may represent a compensatory response.",Aged;Blood Glucose/ metabolism;Brain/ metabolism;Case-Control Studies;Depressive Disorder/metabolism/ radionuclide imaging;Female;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging;Male;Positron-Emission Tomography/ methods;Radiopharmaceuticals,"Smith, G. S.;Kramer, E.;Ma, Y.;Kingsley, P.;Dhawan, V.;Chaly, T.;Eidelberg, D.",2009,Aug,10.1002/gps.2185,0,
1183,The use of technetium-99m-HM-PAO in the assessment of patients with dementia and other neuropsychiatric conditions,"One hundred fourteen patients suffering from neuropsychiatric conditions have been studied using (99m)Tc-labeled hexamethylpropyleneamine oxime (HM-PAO) and single photon emission computed tomography (SPECT). Ninety-one patients had a firm clinical diagnosis while 23 were examined without knowledge of the clinical diagnosis. Of the 91 patients, 51 were suffering from dementia, 25 multi-infarct type and 26 Alzheimer's disease. In 19 of the Alzheimer's patients, a characteristic pattern of decreased perfusion in the parieto-occipital regions was demonstrated while those with multi-infarct type showed varying degrees of irregular uptake in the cerebral cortex. These appearances are similar to those shown with positron emission tomography (PET) and we believe that HM-PAO will provide a widely available method for identifying patients with Alzheimer's disease. Twenty-nine patients were suffering from diseases involving the basal ganglia. Fifteen patients with Parkinson's disease showed no significant abnormality in basal ganglia uptake, while 7 or 8 patients with Huntington's disease who had full examinations showed decreased uptake in the caudate nuclei. Similarly, four of six patients with other basal ganglia diseases showed impaired uptake by basal ganglia, and it is concluded that HM-PAO may be useful for the diagnosis and management of this type of patient. Twenty-three patients received HM-PAO imaging as part of their diagnostic work-up; in 19 of them, detailed follow-up was obtained, which indicated that in 7 cases the result of the HM-PAO scan altered the clinical diagnosis and in 9 cases resulted in a change in management. In the remaining 13 cases, the study was found to be helpful in confirming the diagnosis.",,"Smith, F. W.;Besson, J. A. O.;Gemmell, H. G.;Sharp, P. F.",1988,1988,,0,
1184,Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association,"Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.",AHA Scientific Statements;anticoagulants;brain infarction;cerebrovascular disorders;prevention and control;white matter,"Smith, E. E.;Saposnik, G.;Biessels, G. J.;Doubal, F. N.;Fornage, M.;Gorelick, P. B.;Greenberg, S. M.;Higashida, R. T.;Kasner, S. E.;Seshadri, S.;American Heart Association Stroke, Council;Council on Cardiovascular, Radiology;Intervention;Council on Functional, Genomics;Translational, Biology;Council on, Hypertension",2017,Feb,,0,
1185,Correlations between MRI white matter lesion location and executive function and episodic memory,"OBJECTIVES: MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume. METHODS: Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software. RESULTS: Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally. CONCLUSIONS: Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes.","Aged;Aged, 80 and over;Brain/*pathology;Brain Mapping;Cognition Disorders/*pathology;Executive Function/*physiology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Memory Disorders/*pathology;Mental Recall/*physiology;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Residence Characteristics;*Statistics as Topic","Smith, E. E.;Salat, D. H.;Jeng, J.;McCreary, C. R.;Fischl, B.;Schmahmann, J. D.;Dickerson, B. C.;Viswanathan, A.;Albert, M. S.;Blacker, D.;Greenberg, S. M.",2011,Apr 26,10.1212/WNL.0b013e318217e7c8,0,
1186,"Early cerebral small vessel disease and brain volume, cognition, and gait","OBJECTIVE: Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). METHODS: Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). RESULTS: Mean age was 58 +/- 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. INTERPRETATION: Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.",Adult;Aged;Atrophy/pathology;Brain/ pathology;Canada/epidemiology;Cerebral Small Vessel Diseases/ diagnosis/ physiopathology/psychology;Cognition/ physiology;Early Diagnosis;Female;Gait/ physiology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Organ Size;Population Surveillance/methods;Prospective Studies,"Smith, E. E.;O'Donnell, M.;Dagenais, G.;Lear, S. A.;Wielgosz, A.;Sharma, M.;Poirier, P.;Stotts, G.;Black, S. E.;Strother, S.;Noseworthy, M. D.;Benavente, O.;Modi, J.;Goyal, M.;Batool, S.;Sanchez, K.;Hill, V.;McCreary, C. R.;Frayne, R.;Islam, S.;DeJesus, J.;Rangarajan, S.;Teo, K.;Yusuf, S.",2015,Feb,10.1002/ana.24320,0,
1187,Impaired memory is more closely associated with brain beta-amyloid than leukoaraiosis in hypertensive patients with cognitive symptoms,"BACKGROUND: Hypertension is the strongest modifiable risk factor for subcortical ischemic changes and is also a risk factor for Alzheimer's dementia. We used neuroimaging to investigate the pathological basis of early cognitive symptoms in patients with hypertension. METHODS: In this cross-sectional cohort study 67 patients age >60 years with hypertension and Clinical Dementia Rating scale score of 0.5 without dementia, and without history of symptomatic stroke, underwent MRI for measurement of subcortical vascular changes and positron emission tomography (PET) scan with Pittsburgh Compound B (PiB-PET) to detect beta-amyloid deposition. These imaging measures were related to neuropsychological tests of memory, executive function and processing speed. RESULTS: Mean age was 75.0 (standard deviation, SD, 7.3). Mean neuropsychological Z scores were: episodic memory -0.63 (SD 1.23), executive function -0.40 (SD 1.10), processing speed -0.24 (SD 0.88); 22 of the 67 subjects met criteria for mild cognitive impairment (MCI) and the remaining 45 subjects had subjective cognitive concerns only. In multivariable models adjusting for age and years of education, each 0.1 unit increase in mean cortical PiB-PET binding was associated with 0.14 lower mean Z score for episodic memory (95% CI -0.28 to -0.01). This means that for every 0.1 unit increase in mean cortical PiB-PET, episodic memory was 0.14 standard deviations lower. White matter hyperintensity volume, silent brain infarcts and microbleeds were not associated with neuropsychological test scores. CONCLUSIONS: Episodic memory was prominently affected in hypertensive participants with MCI or subjective cognitive concerns, and was associated with PiB-PET binding. This suggests a prominent role for Alzheimer pathology in cognitive impairment even in hypertensive participants at elevated risk for vascular cognitive impairment.",,"Smith, E. E.;Muzikansky, A.;McCreary, C. R.;Batool, S.;Viswanathan, A.;Dickerson, B. C.;Johnson, K.;Greenberg, S. M.;Blacker, D.",2018,,,0,
1188,Magnetic resonance imaging white matter hyperintensities and brain volume in the prediction of mild cognitive impairment and dementia,"OBJECTIVE: To determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMH), whole-brain atrophy, and cardiovascular risk factors predict the development of cognitive decline and dementia. DESIGN: Subjects were recruited into this prospective cohort study and followed for incident cognitive decline for mean (SD) 6.0 (4.1) years. Magnetic resonance imaging dual-echo sequences, obtained at baseline, were used to determine the volume of WMH and the brain parenchymal fraction (BPF), the proportion of the intracranial cavity occupied by brain. White matter hyperintensity volume was analyzed as the percentage of intracranial volume (WMHr); ""high WMH"" was defined as a WMHr more than 1 SD above the mean. SETTING: General community. PATIENTS: Volunteer sample consisting of 67 subjects with normal cognition and 156 subjects with mild cognitive impairment (MCI). MAIN OUTCOME MEASURES: Time to diagnosis of MCI (among those with normal cognition at baseline) or time to diagnosis of dementia, either all-cause or probable Alzheimer disease (AD) (among those with MCI at baseline). Cox proportional hazards models were used for multivariable analysis. RESULTS: High WMH was a predictor of progression from normal to MCI (adjusted hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.33-8.17; P= .01) but not conversion from MCI to all-cause dementia. Conversely, BPF did not predict progression from normal to MCI but did predict conversion to dementia (adjusted HR, 1.10 for each 1% decrease in BPF; 95% CI, 1.02-1.19; P= .02). When conversion to AD dementia was considered as the outcome, BPF was likewise a predictor (adjusted HR, 1.16 for each 1% decrease in BPF; 95% CI, 1.08-1.24; P< .001), but high WMH was not. Past tobacco smoking was associated with both progression from normal to MCI (adjusted HR, 2.71; 95% CI, 1.12-6.55; P= .03) and conversion to all-cause dementia (adjusted HR, 2.08; 95% CI, 1.13-3.82; P= .02), but not AD dementia. CONCLUSIONS: These findings suggest that WMH are associated with the risk of progressing from normal to MCI. In persons whose cognitive abilities are already impaired, BPF predicts the conversion to dementia.",Aged;Analysis of Variance;Apolipoprotein E4/genetics;Atrophy;Brain/ pathology;Cardiovascular Diseases/epidemiology;Cerebrovascular Disorders/pathology;Cognition Disorders/genetics/ pathology;Dementia/genetics/ pathology;Disease Progression;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prognosis;Prospective Studies;Regression Analysis;Risk Factors;Smoking/adverse effects,"Smith, E. E.;Egorova, S.;Blacker, D.;Killiany, R. J.;Muzikansky, A.;Dickerson, B. C.;Tanzi, R. E.;Albert, M. S.;Greenberg, S. M.;Guttmann, C. R.",2008,Jan,10.1001/archneurol.2007.23,0,
1189,New insights into cerebral small vessel disease and vascular cognitive impairment from MRI,"PURPOSE OF REVIEW: We review recent MRI research that addresses two important challenges in cerebral small vessel disease (SVD) research: early diagnosis, and linking SVD with cognitive impairment. First, we review studies of MRI measurements of blood flow and blood-brain barrier integrity. Second, we review MRI studies identifying neuroimaging correlates of SVD-related cognitive dysfunction, focusing on brain connectivity and white matter microarchitecture. This research is placed in context through discussion of recent recommendations for management of incidentally discovered SVD, and neuroimaging biomarker use in clinical trials. RECENT FINDINGS: Cerebral perfusion, cerebrovascular reactivity (CVR), blood-brain barrier permeability, and white matter microarchitecture are measurable using MRI, and are altered in SVD. Lower cerebral blood flow predicts a higher future risk for dementia, whereas decreased CVR occurs at early stages of SVD and is associated with future white matter hyperintensity growth. Two new approaches to analyzing diffusion tensor imaging (DTI) data in SVD patients have emerged: graph theory-based analysis of networks of DTI connectivity between cortical nodes, and analysis of histograms of mean diffusivity of the hemispheric white matter. SUMMARY: New, advanced quantitative neuroimaging techniques are not ready for routine radiological practice but are already being employed as monitoring biomarkers in the newest generation of trials for SVD.",,"Smith, E. E.;Beaudin, A. E.",2018,Feb,,0,
1190,Prevention of Cerebral Small Vessel Disease,"Cerebral small vessel disease can cause either ischemic stroke or intracerebral hemorrhage. Accounting for up to 25% of all strokes, it is also the second biggest contributor to the risk of dementia, and is the most common incidentally discovered finding on brain imaging. There are two main causes of cerebral small vessel disease: arteriolosclerotic small vessel disease (with hypertension as the main modifiable risk factor) and cerebral amyloid angiopathy (predominantly caused by β-amyloid deposits limited to the cerebral small arteries, arterioles, and capillaries). Prevention should include the treatment of hypertension and diabetes, if present, and the modification of lifestyle factors such as obesity and poor nutrition. Patients with small subcortical ischemic strokes should be treated with antithrombotics; dual antiplatelet therapy may be more effective than aspirin for the first 3 weeks following acute stroke, but is not more effective than aspirin for long-term prevention. Unresolved questions include the effectiveness of nonaspirin prevention strategies to prevent early recurrence or stroke extension in small subcortical ischemic stroke, and whether symptomatic or silent small vessel disease should influence decisions regarding selection for carotid revascularization or anticoagulation for atrial fibrillation. There is an unmet need for disease-modifying preventive therapies for cerebral amyloid angiopathy, the second most-common cause of spontaneous intracerebral hemorrhage.",article;brain hemorrhage;brain injury;brain ischemia;cerebrovascular disease;cognition;disease classification;human;motor performance;neuropathology;primary prevention;priority journal;randomized controlled trial (topic);secondary prevention;small subcortical ischemic stroke,"Smith, E. E.",2017,,10.1055/s-0037-1603468,0,
1191,White matter volumes and periventricular white matter hyperintensities in aging and dementia,"OBJECTIVE: To determine the relationship between MRI periventricular white matter hyperintensities, cerebral white matter volumes, neuropathologic findings, and cognitive status in aged individuals. BACKGROUND: The significance of periventricular white matter hyperintensities seen on MR images in aged individuals remains controversial. The Nun Study is a longitudinal cohort aging study in which all 678 initially enrolled participants agreed to autopsy neuropathologic examination. METHODS: We used MRI to measure white matter volumes of the cerebral hemispheres in 52 formaldehyde-fixed brains for correlation with white matter and neocortical pathology, postmortem MRI observations, and cognitive measures. RESULTS: Reduced white matter volume is associated with dementia, but periventricular white matter hyperintensities were not related to white matter volume, stroke, or dementia. CONCLUSIONS: Our results do not support the hypothesis that periventricular hyperintensities seen on MR images have deleterious consequences in these aged individuals.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology/psychology;Brain/ pathology;Humans;Neuropsychological Tests;Psychiatric Status Rating Scales","Smith, C. D.;Snowdon, D. A.;Wang, H.;Markesbery, W. R.",2000,Feb 22,,0,
1192,Peripheral (deep) but not periventricular MRI white matter hyperintensities are increased in clinical vascular dementia compared to Alzheimer's disease,"BACKGROUND AND PURPOSE: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age. METHODS: Blinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. PVH and dWMH were rated separately and independently by two different examiners using the Scheltens scale. Receiver operator characteristic (ROC) curves were generated using logistic regression to assess classification of VAD (13 patients) versus AD (129 patients). Clinical diagnoses were made in a specialty memory disorders clinic. RESULTS: Using PVH rating alone, overall classification (area under the ROC curve, AUC) was 75%, due only to the difference in age between VAD and AD patients in our study and not PVH. In contrast, dWMH rating produced 86% classification accuracy with no independent contribution from age. A global Longstreth rating that combines dWMH and PVH gave an 88% AUC. CONCLUSIONS: Increased dWMH indicate a higher likelihood of VAD versus AD. Assessment of dWMH on MRI scans using Scheltens and Longstreth scales may aid the clinician in distinguishing the two conditions.",,"Smith, C. D.;Johnson, E. S.;Van Eldik, L. J.;Jicha, G. A.;Schmitt, F. A.;Nelson, P. T.;Kryscio, R. J.;Murphy, R. R.;Wellnitz, C. V.",2016,Mar,10.1002/brb3.438,0,
1193,Age and gender effects on human brain anatomy: a voxel-based morphometric study in healthy elderly,"The adult human brain shrinks slowly with age, but the regional specificity and tissue class specificity of this loss is unclear. Subjects (n=122) were healthy aged participants in a longitudinal cohort who undergo periodic standardized cognitive and clinical examination. Multi-spectral segmentation of magnetic resonance images into grey matter (GM), white matter (WM) and CSF was performed on cross-sectional image data using a custom template and calculated prior probability maps. Global differences were evaluated by fitting a regression model for absolute and normalized subject GM, WM, and CSF values. Global and regional patterns of GM, WM and CSF differences were assessed using optimized voxel-based morphometry (VBM). GM volume decreased with age at a rate of 2.4 cm(3)/year (-0.18%/year); CSF increased by 2.5 cm(3)/year (0.20%/year). Regression analyses showed no significant decrease in WM volume, but a focal WM decrease with age was detected in the anterior corpus callosum using VBM. Diffuse reductions of GM volume were seen with age in the frontal, parietal, and temporal cortex, cerebellum and basal ganglia. Relative regional differences in cortical GM volume with age occurred in the frontal, parietal and temporal lobes, but not in medial temporal lobe or in posterior cingulate. We did not observe significant gender effects. These findings establish a baseline for comparison with pathologic changes in human brain volume between ages 58 and 95 years.","Aged;Aged, 80 and over;Aging/ physiology;Alzheimer Disease/cerebrospinal fluid/pathology;Analysis of Variance;Brain/ anatomy & histology;Cognition Disorders/cerebrospinal fluid/pathology;Female;Geriatric Assessment;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Regression Analysis;Sex Characteristics","Smith, C. D.;Chebrolu, H.;Wekstein, D. R.;Schmitt, F. A.;Markesbery, W. R.",2007,Jul,10.1016/j.neurobiolaging.2006.05.018,0,
1194,White matter diffusion alterations in normal women at risk of Alzheimer's disease,"Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal fasciculi (particularly posteriorly), the splenium of the corpus callosum, subcallosal white matter and the cingulum bundle. These findings demonstrate that specific white matter pathways are altered in normal women at increased risk of AD years before the expected onset of cognitive symptoms.","Aged;Alzheimer Disease/diagnosis/ etiology/ pathology;Apolipoprotein E4/genetics;Brain/metabolism/ pathology;Dementia/diagnosis/etiology/pathology;Diffusion Tensor Imaging;Early Diagnosis;Female;Humans;Image Processing, Computer-Assisted;Middle Aged;Nerve Fibers, Myelinated/metabolism/pathology;Predictive Value of Tests;Risk Factors;Women's Health","Smith, C. D.;Chebrolu, H.;Andersen, A. H.;Powell, D. A.;Lovell, M. A.;Xiong, S.;Gold, B. T.",2010,Jul,10.1016/j.neurobiolaging.2008.08.006,0,
1195,The neuroinflammatory response in humans after traumatic brain injury,"AIMS: Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury. METHODS: This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed 'blind' by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury. RESULTS: A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter. CONCLUSIONS: These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years.",Adolescent;Adult;Age Factors;Aged;Brain/ immunology;Brain Injuries/ immunology/pathology;Humans;Inflammation/immunology/pathology;Microglia/ immunology/pathology;Middle Aged;Young Adult,"Smith, C.;Gentleman, S. M.;Leclercq, P. D.;Murray, L. S.;Griffin, W. S.;Graham, D. I.;Nicoll, J. A.",2013,Oct,10.1111/nan.12008,0,
1196,Validation of automated white matter hyperintensity segmentation,"Introduction. White matter hyperintensities (WMHs) are a common finding on MRI scans of older people and are associated with vascular disease. We compared 3 methods for automatically segmenting WMHs from MRI scans. Method. An operator manually segmented WMHs on MRI images from a 3T scanner. The scans were also segmented in a fully automated fashion by three different programmes. The voxel overlap between manual and automated segmentation was compared. Results. Between observer overlap ratio was 63. Using our previously described in-house software, we had overlap of 62.2. We investigated the use of a modified version of SPM segmentation; however, this was not successful, with only 14 overlap. Discussion. Using our previously reported software, we demonstrated good segmentation of WMHs in a fully automated fashion. © 2011 Sean D. Smart et al.",aged;article;automation;clinical article;software;controlled study;dementia;female;human;image analysis;image processing;intermethod comparison;male;Mini Mental State Examination;nuclear magnetic resonance imaging;priority journal;radiological parameters;three dimensional imaging;white matter;white matter hyperintensity;Intera Achieva;SPM5;Wu program,"Smart, S. D.;Firbank, M. J.;O'Brien, J. T.",2011,,10.4061/2011/391783,0,1197
1197,Validation of automated white matter hyperintensity segmentation,"Introduction. White matter hyperintensities (WMHs) are a common finding on MRI scans of older people and are associated with vascular disease. We compared 3 methods for automatically segmenting WMHs from MRI scans. Method. An operator manually segmented WMHs on MRI images from a 3T scanner. The scans were also segmented in a fully automated fashion by three different programmes. The voxel overlap between manual and automated segmentation was compared. Results. Between observer overlap ratio was 63. Using our previously described in-house software, we had overlap of 62.2. We investigated the use of a modified version of SPM segmentation; however, this was not successful, with only 14 overlap. Discussion. Using our previously reported software, we demonstrated good segmentation of WMHs in a fully automated fashion. © 2011 Sean D. Smart et al.",,"Smart, S. D.;Firbank, M. J.;O'Brien, J. T.",2011,,,0,
1198,Cerebral subcortical small vessel disease and its relation to cognition in elderly subjects: A pathological study in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort,"Background: Subcortical small vessel disease (SVD) is known to contribute to vascular cognitive impairment and vascular dementia, but understanding about the extent of its influence is limited because there is a lack of consensus about how this pathology should be assessed. Methods: In this study we have made use of a simple, novel, image-matching scoring system to assess the extent of SVD in a group of 70 cases from the prospectively assessed Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. These cases were found at autopsy to have cerebrovascular disease and no other pathology except Braak stage 4 or less tau pathology, and insufficient amyloid plaque pathology to meet Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for the diagnosis of Alzheimer's disease. Pathology scores for SVD were correlated with cognitive scores [Mini-Mental State Examination (MMSE) and cognitive section of the Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) (CAMCOG)] at the last clinical assessment before death. Results: The severity of SVD pathology was inversely related to cognitive score before death (P<0.008 for MMSE and P<0.024 for CAMCOG). Thirty-one per cent and 33% of cases were rated as demented by MMSE or CAMCOG respectively. The degree of dementia was generally mild. Age did not influence severity of SVD. Conclusions: An image-based scoring system for SVD in a group of 70 elderly subjects enabled the severity of SVD pathology to be assessed with results that showed a significant correlation between SVD pathology severity and cognitive impairment. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.",,"Smallwood, A.;Oulhaj, A.;Joachim, C.;Christie, S.;Sloan, C.;Smith, A. D.;Esiri, M.",2012,June,,0,
1199,Electroencephalography and single photon emission computed tomography in dementia: a comparative study,"A series of elderly patients with dementia of Alzheimer type (AD), multi-infarct dementia (MID) and functional (non-organic) psychiatric illness (major depressive disorder) were selected according to DSM-III-R criteria and received: a battery of cognitive tests, EEG and Single Photon Emission Computed Tomography (SPECT) using 99mTc HMPAO. The EEG and SPECT scans were examined independently of the clinical data. The former were divided into two abnormal categories, those showing AD type change and vascular change respectively, and a normal group. The SPECT scans were classified as follows: a SPECT rCBF pattern showing bilateral temporoparietal perfusion deficits (AD type); those showing single focal perfusion deficits or multiple areas of low perfusion in the cerebral cortex suggestive of ischaemic change (vascular type SPECT picture); a mixed AD/MID pattern; and those with normal scan findings. There were significant associations between clinical diagnosis, EEG rating and SPECT rCBF pattern, approximately three-quarters of AD and MID patients having the predicted EEG and scan changes. Normal EEG recordings were more common in the MID patients. The two tests agreed in about two-thirds of cases, with no consistent pattern apparent in the cases with divergent findings. Each test misclassified a minority of dementia patients, but in only one patient were both investigations normal. Almost half of the so called 'functionally ill' patients had abnormal rCBF changes, showing mainly vascular changes while one-fifth had abnormal EEGs.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*physiopathology/psychology;Cerebral Cortex/blood supply/*physiopathology;Dementia, Multi-Infarct/diagnosis/*physiopathology/psychology;Depressive Disorder/diagnosis/*physiopathology/psychology;Dominance, Cerebral/physiology;*Electroencephalography;Evoked Potentials/physiology;Female;Geriatric Assessment;Humans;Male;Neuropsychological Tests;Reference Values;Regional Blood Flow/physiology;*Tomography, Emission-Computed, Single-Photon","Sloan, E. P.;Fenton, G. W.;Kennedy, N. S.;MacLennan, J. M.",1995,May,,0,
1200,ACE gene is associated with Alzheimer's disease and atrophy of hippocampus and amygdala,"Despite biological support for a role of angiotensin converting enzyme (ACE) in Alzheimer's disease (AD), studies assessing the ACE I/D polymorphism in AD are conflicting. We re-evaluated this association in the Rotterdam Study, a population-based cohort study. The mechanism of association was further explored by adjusting for vascular factors, and by analysing atrophy, white matter lesions and infarcts on MRI in non-demented individuals. Genotypes were available for 6488 participants. During average follow-up of 6 years 250 subjects developed AD. MRI data were available for 494 non-demented participants. Homozygosity for the I-allele conferred a slightly increased risk of AD compared to carrying a D-allele (RR 1.12 (95% CI 0.99-1.25)). This increase was only significant in women, and independent of vascular factors (RR 1.39 (95% CI 1.14-1.69)). Non-demented women with the II genotype had smaller hippocampal and amygdalar volumes. Vascular pathology was not significantly associated with ACE. This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors.","Aged;Alzheimer Disease/enzymology/*genetics/pathology;Amygdala/*pathology;Atrophy/enzymology/*genetics/pathology;Cerebrovascular Disorders/enzymology/genetics/pathology;Cohort Studies;DNA Mutational Analysis;Female;Genetic Predisposition to Disease/genetics;Genetic Testing;Genotype;Hippocampus/*pathology;Homozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Netherlands;Peptidyl-Dipeptidase A/*genetics;Polymorphism, Genetic/*genetics;Sex Factors","Sleegers, K.;den Heijer, T.;van Dijk, E. J.;Hofman, A.;Bertoli-Avella, A. M.;Koudstaal, P. J.;Breteler, M. M.;van Duijn, C. M.",2005,Aug-Sep,10.1016/j.neurobiolaging.2004.09.011,0,
1201,The influence of vascular risk factors and white matter hyperintensities on the degree of cognitive impairment in Parkinson's disease,"BACKGROUND AND PURPOSE: Vascular risk factors may contribute to deterioration of cognitive functions in Alzheimer's disease and vascular (or mixed) dementia. Parkinson's disease (PD) is an age-related disorder and vascular risk factors potentially might be the main co-morbidity responsible for motor and cognitive impairment. However, only a few studies focused on this problem have been published. The aim of the study was to assess the contribution of vascular risk factors and white matter abnormalities in magnetic resonance imaging (MRI) on cognitive impairment in PD patients. MATERIAL AND METHODS: Sixty consecutive patients (M: 35, F: 25), mean age 68.36 years (SD: 7.25, range: 51-81) with diagnosis of idiopathic PD underwent a semi-structured questionnaire on demographics and vascular risks factors, neurological, neuropsychological and neuroimaging (MRI) examinations with quantitative assessment according to the scale by Wahlund et al. According to cognitive status they were divided into 3 groups: without cognitive disability (I, n=17), with mild cognitive impairment (II, n=25) and with dementia (III, n=18). RESULTS: There were no significant differences between groups in terms of the number of vascular risk factors (except for the ischaemic heart disease difference between group I and III) and severity of white matter hyperintensities in MRI studies. CONCLUSIONS: Vascular risk factors along with white matter vascular abnormalities probably do not contribute to cognitive impairment in patients with PD. This is in concordance with previously published studies.","Adult;Aged;Aged, 80 and over;Cerebrovascular Disorders/ complications/ pathology;Cognition Disorders/ etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurologic Examination/methods;Parkinson Disease/ complications/ pathology;Poland;Predictive Value of Tests;Prefrontal Cortex/pathology;Psychomotor Performance;Risk Factors;Severity of Illness Index","Slawek, J.;Wieczorek, D.;Derejko, M.;Dubaniewicz, M.;Brockhuis, B.;Sitek, E.;Wilczewska, L.;Roszmann, A.;Lass, P.",2008,Nov-Dec,,0,
1202,The Impact of MRI white matter hyperintensities on dementia in parkinson's disease in relation to the homocysteine level and other vascular risk factors,"Background: The role of white matter hyperintensities (WMH) and homocysteine (Hcy) and other vascular risk factors in the pathogenesis of Parkinson's disease (PD) dementia (PDD) remains unclear. Objective: The aim of the study was to assess the impact of WMH, Hcy and other biochemical and vascular risk factors on PDD. Methods: A total of 192 patients with PD and 184 age-and sex-matched healthy controls were included. A semistructured interview was used to assess demographic and clinical variables with respect to vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, ischemic heart disease, obliterative atherosclerosis, hypercholesterolemia, smoking, alcohol intake). Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging and the Schwab-England activities of daily living scale were used to assess motor abilities and activities of daily living. A complex neuropsychological examination with a battery of tests was used to classify patients into a group with dementia (PDD) and a group without dementia (PD). Neuroradiological examination of MRI scans included visual rating scales for WMH (according to the Wahlund and Erkinjunntti rating scales) and the Scheltens scale for hippocampal atrophy. Blood samples for Hcy, folate, vitamin B12, fibrinogen, lipids, glucose, creatinine, transaminases and thyroid stimulating hormone (TSH) were examined. Results: Among all patients, 57 (29.7%) fulfilled the diagnostic criteria for dementia. Significantly higher Hcy plasma levels were noted in PD and PDD groups compared to controls (p < 0.05) and in PDD when compared to PD (p < 0.05). According to multivariate regression analysis, WMH (Erkinjuntti scale), high Hcy, low vitamin B12 and folate plasma levels were independent risk factors for PDD. Vascular risk factors did not play any role in the pathogenesis of PDD and WMH. Conclusions: WMH along with Hcy, folate and vitamin B12 may impact cognition in PD. Therapy with vitamin B12, folate and catechol-O-methyltransferase inhibitors may play a potential protective role against PDD.",aminotransferase;catechol methyltransferase inhibitor;creatinine;cyanocobalamin;fibrinogen;folic acid;glucose;homocysteine;levodopa;lipid;thyrotropin;activity of daily living assessment;adult;aged;alcohol consumption;article;atherosclerosis;Beck Depression Inventory;blood sampling;brain atrophy;controlled study;dementia;diabetes mellitus;female;atrial fibrillation;hippocampus;human;hypercholesterolemia;hypertension;ischemic heart disease;major clinical study;male;Mini Mental State Examination;motor performance;neuroradiology;nuclear magnetic resonance imaging;Parkinson disease;priority journal;rating scale;risk factor;semi structured interview;smoking;Unified Parkinson Disease Rating Scale;white matter,"Sławek, J.;Roszmann, A.;Robowski, P.;Dubaniewicz, M.;Sitek, E. J.;Honczarenko, K.;Gorzkowska, A.;Budrewicz, S.;Mak, M.;Gołąb-Janowska, M.;Koziorowska-Gawron, E.;Droździk, M.;Kurzawski, M.;Bandurski, T.;Białecka, M.",2014,,,0,
1203,ApoE influences regional white-matter axonal density loss in Alzheimer's disease,"Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) epsilon4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE epsilon4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in epsilon4+ individuals but more focal (posterior predominant) in the absence of an epsilon4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEepsilon4 status is associated with different patterns of white-matter neurodegeneration.",0 (Apolipoprotein E4);Aged;Alzheimer Disease/diagnostic imaging/ genetics/ pathology/psychology;Apolipoprotein E4;Axons/ pathology;Diffusion Tensor Imaging;Female;Genetic Association Studies;Humans;Intelligence;Male;Middle Aged;Neurites/pathology;Phenotype;Spatial Processing;White Matter/ diagnostic imaging/ pathology;Alzheimer's disease;Apoe;Neurite orientation dispersion and density imaging;White matter,"Slattery, C. F.;Zhang, J.;Paterson, R. W.;Foulkes, A. J. M.;Carton, A.;Macpherson, K.;Mancini, L.;Thomas, D. L.;Modat, M.;Toussaint, N.;Cash, D. M.;Thornton, J. S.;Henley, S. M. D.;Crutch, S. J.;Alexander, D. C.;Ourselin, S.;Fox, N. C.;Zhang, H.;Schott, J. M.",2017,Sep,,0,
1204,Co-existing spinal canal tumours and CADASIL - A diagnostic challenge,"We would like to present a case of a 51-year-old patient with two rare co-existing diseases. The patient was suffering from two tumours in the lumbar region of the spinal canal, which caused development of hydrocephalus. Diffuse white, matter hyperintensities, (WMH) were observed in our patient's brain imaging. She was also suffering, from headaches and she had two mild strokes. We performed some further diagnostic procedures and found out that the patient was suffering from CADASIL. CADASIL was confirmed by both ultrustructural analysis and genetic testing.",,"Skowrońska, M.;Lewandowska, E.;Członkowska, A.",2006,2006,,0,
1205,The prevalence of white-matter lesions on computed tomography of the brain in demented and nondemented 85-year olds,"The prevalence of white-matter lesions on computed tomography was studied in a representative sample of 85-year-olds living in Gothenburg, Sweden. The study included a psychiatric examination, interview of a close informant, neuropsychological examination, physical examination, comprehensive laboratory tests, electrocardiogram, chest X-ray, computed tomography scan of the head, and cerebrospinal fluid analysis. The diagnoses of dementia and other mental disorders were made according to DSM-III-R criteria. The prevalence of white-matter lesions in demented subjects was 68.9%, and in nondemented, 33.8%. Their prevalence was not increased in any mental disorder other than dementia. All severities of dementia and the subtypes, Alzheimer's disease, vascular dementia, and other types of dementia, had a significantly higher prevalence of white-matter lesions than did nondemented subjects. The risk for dementia, but not its severity, increased with the severity of these lesions. A stepwise logistic regression analysis showed that both white-matter lesions and infarcts on computed tomography contributed independently to dementia. White-matter changes may be a contributing cause of dementia in the oldest old, or may represent a disease entity of its own. They are important to recognize since they may be potentially preventable, or even treatable.",aged;Alzheimer disease;article;brain injury;brain tomography;cerebrospinal fluid analysis;controlled study;dementia;disease severity;electrocardiography;human;interview;laboratory test;mental disease;neuropsychological test;physical examination;priority journal;regression analysis;Sweden;thorax radiography;white matter,"Skoog, I.;Palmertz, B.;Andreasson, L. A.",1994,,,0,
1206,Head size may modify the impact of white matter lesions on dementia,"We aimed to examine whether total intracranial volume (TICV), a marker of premorbid brain size, modified the impact of the apolipoprotein E (apoE) e4 phenotype and ischemic white matter lesions (WMLs) on odds for dementia. The study comprised a population-based sample of 104 demented and 135 nondemented 85-year-olds, and included physical and neuropsychiatric examinations, and head computerized tomography (CT). Dementia disorders were defined according to standard criteria. TICV and WMLs were rated on computerized tomography. Using the highest group as reference, the risk for dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was increased in those with the smallest half, tertile, and quartile of TICV. Smaller TICV increased the odds of dementia, Alzheimer's disease, and vascular dementia in participants with WMLs. WMLs were not associated with increased odds of dementia in those with the largest TICV. The interaction term WMLs*TICV was also significant. TICV did not modify the odds of dementia in those with the apolipoprotein e4 phenotype. Our results suggest that the impact of brain pathology on the risk of dementia is modified by premorbid brain size.","Aged, 80 and over;Brain/*pathology;Dementia/*diagnosis/epidemiology/psychology;Female;Head/pathology;Humans;Male;Nerve Fibers, Myelinated/*pathology;Organ Size;Population Surveillance/methods;Skull/pathology","Skoog, I.;Olesen, P. J.;Blennow, K.;Palmertz, B.;Johnson, S. C.;Bigler, E. D.",2012,Jul,10.1016/j.neurobiolaging.2011.01.011,0,
1207,A population-based study of dementia in 85-year-olds,"Background. The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden. Methods. The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history. Results. The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three- year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent). Conclusions. Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.",aged;Alzheimer disease;article;cerebrospinal fluid analysis;computer assisted tomography;dementia;disease severity;female;human;institutionalization;interview;major clinical study;male;mortality;multiinfarct dementia;physical examination;population research;prevalence;priority journal;psychologic test;rating scale;Sweden,"Skoog, I.;Nilsson, L.;Palmertz, B.;Andreasson, L. A.;Svanborg, A.",1993,,,0,
1208,15-year longitudinal study of blood pressure and dementia,"BACKGROUND: Vascular causes of dementia may be more common than supposed. Vascular factors may also have a role in late-onset Alzheimer's disease, but the role of hypertension in the development of dementia is unclear. METHODS: As part of the Longitudinal Population Study of 70-year-olds in Goteborg, Sweden, we analysed the relation between blood pressure and the development of dementia in the age intervals 70-75, 75-79, and 79-85 years in those non-demented at age 70 (n = 382). The sample was followed up for 15 years and examined repeatedly with a comprehensive investigation, including a psychiatric and physical examination. a FINDINGS: Participants who developed dementia at age 79-85 had higher systolic blood pressure at age 70 (mean 178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages 70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did not develop dementia. For subtypes of dementia, higher diastolic blood pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's disease and at age 75 (101, p = 0.015) for those developing vascular dementia than for those who did not develop dementia. Participants with white-matter lesions on computed tomography at age 85 had higher blood pressure at age 70 than those without such lesions. Blood pressure declined in the years before dementia onset and was then similar to or lower than that in non-demented individuals. INTERPRETATION: Previously increased blood pressure may increase the risk for dementia by inducing small-vessel disease and white-matter lesions. To what extent the decline in blood pressure before dementia onset is a consequence or a cause of the brain disease remains to be elucidated.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/etiology/physiopathology/radiography;Blood Pressure/*physiology;Brain/radiography;Dementia/etiology/*physiopathology/radiography;Dementia, Vascular/etiology/physiopathology/radiography;Humans;Hypertension/complications;Longitudinal Studies;Tomography, X-Ray Computed","Skoog, I.;Lernfelt, B.;Landahl, S.;Palmertz, B.;Andreasson, L. A.;Nilsson, L.;Persson, G.;Oden, A.;Svanborg, A.",1996,Apr 27,,0,
1209,"Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects: Relation to dementia, apolipoprotein E polymorphism, cerebral atrophy, and white matter lesions","Objective: To further elucidate the pathogenetic role of apolipoprotein E (Apo E) in degenerative brain disorders, we analyzed cerebrospinal fluid (CSF) levels of Apo E in 85-year-old subjects with dementia disorders. Design: Survey. Setting: Community. Participants: Population-based sample of 27 demented (12 with Alzheimer disease [AD]; 13, vascular dementia [VAD]; and 2, other types of dementia) and 35 nondemented individuals. Main Outcome Measures: Cerebrospinal fluid levels of Apo E, Apo E polymorphism, and brain atrophy and white matter lesions (WMLs) measured by computed tomography (CT) of the brain. Dementia was defined according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria; AD, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria; and VAD, National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neuroscience criteria. Results: The mean (± SD) CSF levels of Apo E were lower in the AD (2.6±1.5 mg/L; P<.02) and VAD groups (2.5±0.9 mg/L; P<.002) than in the nondemented group (3.8±1.7 mg/L). Cerebrospinal fluid levels of Apo E decreased with increasing severity of dementia and with increasing temporal cortical and central frontal atrophy. In nondemented individuals, CSF levels of Apo E decreased with increasing degree of WMLs. Cerebrospinal fluid levels of Apo E were not influenced by the Apo E4 isoform. Conclusions: Whether our finding of an association between low CSF levels of Apo E and dementia disorders (both degenerative, such as AD, and vascular, such as VAD) is related to the pathogenesis of these disorders or is a secondary consequence of the disease process remains to be established. Although statistical correlations do not give direct evidence of causal relations, the correlations between CSF level of Apo E and severity of dementia and cortical atrophy suggest that CSF level of Apo E follows the disease process.",apolipoprotein E;age;aged;Alzheimer disease;article;blood brain barrier;brain atrophy;cerebrospinal fluid analysis;computer assisted tomography;controlled study;dementia;female;genetic polymorphism;human;human tissue;major clinical study;male;multiinfarct dementia;priority journal;white matter,"Skoog, I.;Hesse, C.;Fredman, P.;Andreasson, L. A.;Palmertz, B.;Blennow, K.",1997,,,0,
1210,"A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality","OBJECTIVES: To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. METHODS: A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. RESULTS: At the age of 85, carriers of the apoE epsilon4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE epsilon4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE epsilon4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE epsilon4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE epsilon4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The epsilon2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05). CONCLUSIONS: Neither the apoE epsilon4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia substantially.","Aged;*Aged, 80 and over;Apolipoproteins E/*genetics;Cerebrovascular Disorders/epidemiology/*genetics;Dementia/classification/epidemiology/*genetics;Follow-Up Studies;*Gene Frequency;*Heterozygote;Humans;*Mortality;Odds Ratio;Risk Factors;Sweden/epidemiology","Skoog, I.;Hesse, C.;Aevarsson, O.;Landahl, S.;Wahlstrom, J.;Fredman, P.;Blennow, K.",1998,Jan,,0,
1211,Update on hypertension and Alzheimer's disease,"Several studies report that blood pressure is increased in victims of Alzheimer's disease (AD) decades before the onset of the disease. Years before onset of Alzheimer's disease, blood pressure start to decrease and continues to decrease during the disease process. High blood pressure has also been related to pathological manifestations of Alzheimer's disease (senile plaques, neurofibrillary tangles, hippocampal atrophy). The exact mechanism behind these associations is not clear. Hypertension is also a risk factor for stroke, ischemic white matter lesions, silent infarcts, general atherosclerosis, myocardial infarction and cardiovascular diseases, and often clusters with other vascular risk factors, including diabetes mellitus, obesity and hypercholesterolemia. Also these risk factors have been related to Alzheimer's disease. Hypertension may thus cause cerebrovascular disease that may increase the possibility for individuals with AD encephalopathy to express a dementia syndrome. Hypertension may also lead to vessel wall changes in the brain, leading to hypoperfusion, ischemia and hypoxia which may initiate the pathological process of AD. Finally, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Several observational studies have reported that use of antihypertensives decreases risk of AD. Even though hypertension only results in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of demented individuals. © 2006 W. S. Maney & Son Ltd.",angiotensin receptor antagonist;antihypertensive agent;apolipoprotein E4;atenolol;beta adrenergic receptor blocking agent;calcium channel blocking agent;candesartan hexetil;chlortalidone;cholinesterase inhibitor;dipeptidyl carboxypeptidase inhibitor;diuretic agent;indapamide;nitrendipine;perindopril;placebo;adult;aged;Alzheimer disease;antihypertensive therapy;article;blood pressure;brain atrophy;brain blood flow;brain blood vessel;cerebrovascular disease;cognitive defect;controlled study;dementia;disease association;disease severity;hippocampus;human;hypertension;major clinical study;neurofibrillary tangle;neuroimaging;neuropathology;nuclear magnetic resonance imaging;pathogenesis;risk factor;cerebrovascular accident;treatment outcome,"Skoog, I.;Gustafson, D.",2006,,,0,
1212,The influence of white matter lesions on neuropsychological functioning in demented and non-demented 85-year-olds,"White matter lesions on computed tomography of the head were studied in relation to neuropsychological functioning in subjects from a representative sample of non-demented (n = 134) and demented (n = 98) 85-year-olds. Non-demented subjects with white matter lesions (n = 46) scored significantly lower in tests of verbal ability (Synonyms), spatial ability (Block Design, Clock Test), perceptual speed (Identical forms), secondary memory (Thurstone Picture Memory), basic arithmetic (Coin Test) and the global cognitive screening test Mini-Mental State Examination than non-demented subjects without white matter lesions (n = 88). Demented subjects with white matter lesions (n = 67) scored significantly lower in tests of spatial ability (Block Design and Clock Test) and secondary memory (free recall in the MIR memory test, Ten-word memory test I and II) and in the Mini-Mental State Examination than demented subjects without white matter lesions (n = 31). It is concluded that white matter lesions contribute to cognitive decline in both non-demented and demented elderly subjects.","Aged;Aged, 80 and over;Brain/pathology;Cerebral Ventricles/pathology;Dementia/*diagnosis/pathology/psychology;Demyelinating Diseases/*diagnosis/pathology/psychology;Female;Humans;Longitudinal Studies;Male;Mental Status Schedule;*Neuropsychological Tests;Reference Values;Sweden;*Tomography, X-Ray Computed","Skoog, I.;Berg, S.;Johansson, B.;Palmertz, B.;Andreasson, L. A.",1996,Feb-Mar,,0,
1213,Metachromatic leukodystrophy (MLD). XV. Adult MLD with focal lesions by computed tomography,"A 31-year-old woman with adult metachromatic leukodystrophy was seen for a progressive dementia. Computed tomographic scans showed four, nearly mirror-image, hypoabsorptive areas in cerebral white matter. These symmetric bifrontal and biparietal abnormalities were accompanied by mild ventricular enlargement and by a slight to moderate volume loss throughout the brain. Diffuse white-matter abnormalities of a kind that might otherwise be anticipated in the usual childhood leukodystrophy were not seen.",,"Skomer, C.;Stears, J.;Austin, J.",1983,1983,,0,
1214,Symptomatological characteristics distinguish between frontotemporal dementia and vascular dementia with a dominant frontal lobe syndrome,"OBJECTIVE: Our hypothesis was that patients with vascular dementia and a dominating frontal lobe syndrome have a symptomatology that reflects a more widespread lesion compared with patients with frontotemporal dementia. DESIGN: Patients with vascular dementia and a dominating frontal lobe syndrome (VAD-F; N = 11) were compared with regard to clinical symptoms and imaging features on CT scans of the brain with patients with frontotemporal dementia (FTD; N = 21). SETTING: A neuropsychiatric diagnostic ward. PATIENTS: Thirty-two inpatients, aged 48-78 years, with frontotemporal dementia or vascular dementia. MEASURES: Relatives were questioned about the initial symptoms. At the clinical investigation, mental and neurological symptoms and signs were recorded using the STEP method (stepwise comparative status analysis). CT scan features of the brain were evaluated by a trained neuroradiologist. The GBS-i (Gottfries-Brane-Steen, intellectual variables) scale was used to measure the degree of dementia. RESULTS: At the onset of dementia, loss of memory (p < 0.001), sudden onset (p < 0.001), confusion (p < 0.05) and unspecified neurological signs (p < 0.05) had been significantly more frequent in the VAD-F group. At the time of the clinical investigation, lack of social awareness and presence of primitive reflexes were more frequent in the FTD group (p < 0.01 and p < 0.05, respectively) and visuospatial deficits more frequent in the VAD-F group (p < 0.05). CT of the brain showed that, apart from brain infarcts (present only in the VAD-F group), paraventricular leukoaraiosis was significantly more pronounced in the VAD-F group (p < 0.05). The groups did not differ with respect to age, age at onset or level of dementia. CONCLUSION: The findings support our hypothesis.","Age of Onset;Aged;Confusion/complications;Dementia/complications/ diagnosis/physiopathology;Dementia, Vascular/complications/ diagnosis/physiopathology;Diagnosis, Differential;Disease Progression;Female;Frontal Lobe/physiopathology;Humans;Male;Memory Disorders/complications;Middle Aged;Social Behavior Disorders/complications;Tomography, X-Ray Computed","Sjogren, M.;Wallin, A.;Edman, A.",1997,Jun,,0,
1215,Frontotemporal dementia can be distinguished from Alzheimer's disease and subcortical white matter dementia by an anterior-to-posterior rCBF-SPET ratio,"Sixteen patients with frontotemporal dementia (FTD), 27 with early-onset Alzheimer's disease, 25 with late-onset Alzheimer's disease, 19 with subcortical white matter dementia (SWD) and 28 normal controls underwent semiquantitative regional cerebral blood flow measurement (rCBF) using single-photon emission tomography (SPET; (99m)Tc-HMPAO) and either computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain. An anterior-to-posterior rCBF-SPET ratio (mesial superior frontal gyrus/medial temporal lobes) was calculated, which significantly separated the FTD group from the other dementia groups and controls with a sensitivity of 87.5% and a specificity of at least 78.6%. CT/MRI was found to be helpful in the differential diagnosis between FTD and SWD. In FTD patients, the mesial superior frontal gyrus, near the polus frontalis, was found to be the region with the most reduced rCBF values. Copyright (C) 2000 S. Karger AG, Basel.",,"Sjögren, M.;Gustafson, L.;Wikkelsö, G.;Wallin, A.",2000,2000,,0,
1216,Increased intrathecal inflammatory activity in frontotemporal dementia: Pathophysiological implications,"Objective: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such mechanisms has been presented. The aim of this study was to compare the cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α, and the anti-inflammatory cytokine transforming growth factor (TGF)-β in patients with FTD and normal controls. Furthermore, serum levels of TNF-α, TGF-β, and IL-1β were measured in FTD patients. Methods: The CSF levels of IL-1β, TNFα, and TGF-β were measured using ELISA in 19 patients with FTD and 24 sex and age matched healthy controls. Results: The CSF levels of TNF-α (FTD 0.6 pg/mL (median: lower, upper quartile 0.3, 0.7); controls: 0.0 pg/mL (0.0, 0.0); p = 0.008) and TGF-β (FTD 266 pg/mL (157, 371), controls: 147 pg/mL (119, 156); p = 0.0001) were significantly increased in FTD patients compared with controls. No correlations were found between CSF and serum levels of the cytokines. In the controls, but not in the FTD patients, a positive correlation was found between the CSF levels of TGF-β and age (r = 0.42, p<0.05). No correlation was found between any of the cytokines and degree of brain atrophy or white matter changes. No differences between the groups were found for age, gender, or CSF/serum albumin ratio. Conclusions: The results suggest an increased intrathecal production of both pro- and anti-inflammatory cytokines in FTD. As no correlations were found with the albumin ratio, and no correlations between CSF and serum levels of the cytokines were found, these changes in the CSF cannot be explained by a systemic overproduction of cytokines.",interleukin 1beta;transforming growth factor beta;tumor necrosis factor alpha;adult;age distribution;aged;article;brain atrophy;comparative study;computer assisted tomography;controlled study;enzyme linked immunosorbent assay;female;frontotemporal dementia;human;inflammation;major clinical study;male;nuclear magnetic resonance imaging;pathophysiology;priority journal;protein cerebrospinal fluid level;sex difference;white matter,"Sjögren, M.;Folkesson, S.;Blennow, K.;Tarkowski, E.",2004,,,0,
1217,Neurofilament protein in cerebrospinal fluid: a marker of white matter changes,"The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.","Aged;Alzheimer Disease/*cerebrospinal fluid/pathology/physiopathology;Amyloid beta-Peptides/*cerebrospinal fluid;Apolipoprotein E4;Apolipoproteins E/genetics;Biomarkers/cerebrospinal fluid;Cerebral Cortex/*metabolism/pathology/physiopathology;Dementia, Vascular/cerebrospinal fluid/pathology/physiopathology;Diagnosis, Differential;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*metabolism/pathology;Neurofilament Proteins/*cerebrospinal fluid;Peptide Fragments/*cerebrospinal fluid;Predictive Value of Tests;Serum Albumin/metabolism;Sex Factors;Wallerian Degeneration/cerebrospinal fluid/pathology/physiopathology;tau Proteins/*cerebrospinal fluid","Sjogren, M.;Blomberg, M.;Jonsson, M.;Wahlund, L. O.;Edman, A.;Lind, K.;Rosengren, L.;Blennow, K.;Wallin, A.",2001,Nov 1,,0,
1218,White matter mapping in Alzheimer's disease: A neuropathological study,"White matter disease (WMD) with pervasive non-focal subtotal tissue loss is frequently seen in Alzheimer's disease (AD) upon neuropathological examination. Although WMD has varying effects on AD symptoms, accurate clinical detection is difficult due partly to scarcity of correlative structural imaging and histopathological studies. Neuropathological studies of WMD severity and distribution have been conducted earlier using semi-quantitative methods. A technique for quantifying WMD objectively in large white matter areas, based on optical density (OD) measurements on images of scanned whole-brain sections, was developed and was validated using conventional microscopic assessment. Altogether, 16 AD cases with concomitant WMD (AD-WMD) and 9 cases of AD without WMD (AD-only) were analysed. The OD values correlated significantly with the neuropathological severity of WMD and were significantly lower in AD-WMD than in AD-only in frontal, frontoparietal, temporal and parietal white matter but not in the occipital white matter, the frontal OD difference being greatest. Useful baseline information on WMD distribution in AD to relate to in vivo imaging results was obtained.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Brain Mapping;Densitometry;Female;Histocytochemistry;Humans;Male;Middle Aged;Organ Size","Sjobeck, M.;Haglund, M.;Englund, E.",2006,May,10.1016/j.neurobiolaging.2005.03.007,0,
1219,Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease--a neuropathological study,"BACKGROUND: White matter disease (WMD) is frequently seen in Alzheimer's disease (AD) at neuropathological examination. It is defined as a subtotal tissue loss with a reduction of myelin, axons and oligodendrocytes as well as astrocytosis. Studies quantitatively defining the myelin loss in AD are scarce. The aim was to develop a method that could provide numerical values of myelin density in AD. The purpose was to compare the myelin contents in increasing grades of pathology of WMD, with age and cortical AD pathology as well as in different regions of the brain in AD. MATERIAL AND METHODS: Sixteen cases with AD and concomitant WMD were investigated with an in-house developed image analysis technique to determine the myelin attenuation with optical density (OD) in frontoparietal, parietal, temporal and occipital white matter on whole brain coronal sections stained for myelin with Luxol Fast Blue (LFB). The OD values in LFB were compared grouped according to Haematoxylin/Eosin (HE) evaluated mild, moderate and severe WMD or normal tissue. The OD values were also correlated with age and cortical AD pathology and compared between the different studied white matter regions. RESULTS: Increasing severity of WMD was associated with a statistically significant OD reduction. No correlation was seen between age and OD or overall cortical AD pathology. The OD values were significantly lower in frontoparietal-compared to occipital white matter. CONCLUSIONS: Myelin loss in AD with WMD is a marked morphologic component of the disease and it is possible to determine the reduction objectively in neuropathological specimens with quantitative measures. This may be of use for clinical diagnostics including brain imaging.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Cerebral Cortex/pathology;Humans;Image Processing, Computer-Assisted/methods;Male;Middle Aged;Myelin Sheath/ pathology;Photography/methods;Severity of Illness Index","Sjobeck, M.;Haglund, M.;Englund, E.",2005,Oct,10.1002/gps.1384,0,
1220,Glial levels determine severity of white matter disease in Alzheimer's disease: a neuropathological study of glial changes,"The morphological components of cerebral white matter disease (WMD) were studied in 17 cases of clinically diagnosed dementia and neuropathologically verified Alzheimer's disease (AD) with concomitant WMD. The distribution of grey and white matter changes was evaluated and overall as well as regional severity was graded. Total glial numbers in frontal white matter were counted using a light microscope. Oligodendrocyte and astrocyte quantities as well as astrocytic reactivity were assessed from frontal and parietal lobe white matter using a computer assisted morphometric method. The AD-WMD group was compared with 10 nondemented age-matched controls. Astrocyte/oligodendrocyte ratio (AOR) was calculated, total glial counts and AOR were compared with severity of WMD, and Alzheimer encephalopathy grade was subjectively assessed. Astrocytic numbers, AOR and astrocytic reactivity proved to be significantly higher in the demented group, whereas oligodendrocytic and total glial counts were significantly lower. Furthermore, AOR proved to be positively correlated with severity of WMD, whereas no association was found with Alzheimer encephalopathy. We conclude that WMD in dementia, for example, of the type seen in AD, can easily be detected, measured and graded quantitatively, with AOR being a significant indicator of the severity of changes. This could serve as a tool for differentiating white matter pathologies in dementia and may be the basis for recognition of the mildest white matter changes with new imaging methods, and enable potential clinical intervention.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Astrocytes/pathology;Brain/ pathology;Cell Count;Humans;Image Processing, Computer-Assisted;Middle Aged;Neuroglia/ pathology;Oligodendroglia/pathology","Sjobeck, M.;Englund, E.",2003,Apr,,0,
1221,Alzheimer's disease (AD) and executive dysfunction. A case-control study on the significance of frontal white matter changes detected by diffusion tensor imaging (DTI),"White matter (WM) changes are frequently seen on structural imaging in AD but the clinical relevance of these changes is uncertain. Frontal WM pathology is often observed upon neuropathological examination in AD. Since frontal cortical/sub-cortical pathology is known to relate to executive dysfunction, the aim was to elucidate if frontal WM changes in AD correlated with executive dysfunction. In all, 15 AD patients and 15 age-matched control cases were investigated in the study, which covered conventional magnetic resonance imaging (MRI), DTI, neuropsychiatric and neuropsychological examinations. Reduced performance on neuropsychological testing of executive function correlated significantly with an increasing degree of frontal WM changes detected by DTI in the AD group, while no such correlation was observed for the controls. Conventional semi-quantitative MRI assessment did not correlate with results on neuropsychological testing of executive function in any of the groups. The structural correlate to certain dimensions of executive dysfunction in AD patients could be related to changes in the deep frontal WM. DTI appears to be more sensitive in the detection of clinically significant WM alterations than conventional semi-quantitative MRI.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Case-Control Studies;Diffusion Tensor Imaging;Executive Function;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Matched-Pair Analysis;Neuropsychological Tests;Sensitivity and Specificity;Statistics, Nonparametric","Sjobeck, M.;Elfgren, C.;Larsson, E. M.;Brockstedt, S.;Latt, J.;Englund, E.;Passant, U.",2010,May-Jun,10.1016/j.archger.2009.03.014,0,
1222,Symptomatic seizures in neurosyphilis: an experience from a university hospital in south India,"PURPOSE: Neurosyphilis has protean clinical manifestations, including epilepsy. However, there is paucity of literature providing details regarding seizures. The aim of the study was to analyze the clinical profile and brain imaging features of 30 patients of neurosyphilis, and to evaluate the predictors and the outcome of seizures in this subgroup. PATIENT AND METHODS: Among the 119 patients (M:F:: 84:35) of neurosyphilis, evaluated over 6 years, 30 patients (M:W::23:7, age: 37.5+/-10.1 years, duration of illness: 11.9+/-20.1 months) were reported to have seizures. CSF-VDRL was positive in all. In addition, HIV serology was positive in 2/20. RESULTS: Seizure was the dominant symptom in all and lone manifestation in two patients. None had history of epilepsy. Their seizure profile was: generalized (17), partial (8), and status epilepticus (5). Concomitant manifestations were encephalopathy (7), meningitis (7), dementia (6), behavioral disturbances (4), stroke (2), and optic atrophy (1). CSF study revealed pleocytosis in 24 (34.6+/-51.5/cu mm) and raised protein in 20 (67+/-33.3mg%). CT scan was abnormal in 26 patients and revealed diffuse atrophy in all and focal hypodensities in 5 patients. MRI of brain (6) showed features of ischemia (2), meningeal enhancement (1) and white matter (1) and medial temporal (2) signal changes. Three patients had reversible periodic lateralized epileptiform discharges (PLEDs), without structural lesion. Nineteen patients received penicillin and/or ceftriaxone. At a mean follow up of 6.7+/-9.4 months, 13/17 had variable improvement. Nine patients required polytherapy and seizures remained uncontrolled in five patients. CONCLUSIONS: Symptomatic seizures due to neurosyphilis are frequent, may have diverse underlying mechanism(s) and rarely can be the lone manifestation. In view of availability of specific therapy for syphilis, a high index of suspicion is recommended.","Adult;Electroencephalography/methods;Female;Hospitals, University;Humans;India/epidemiology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neurosyphilis/ complications/epidemiology;Retrospective Studies;Seizures/diagnosis/ etiology;Young Adult","Sinha, S.;Harish, T.;Taly, A. B.;Murthy, P.;Nagarathna, S.;Chandramuki, A.",2008,Dec,10.1016/j.seizure.2008.05.003,0,
1223,Calcified Amorphous Tumor Causing Shower Embolism to the Brain: A Case Report with Serial Echocardiographic and Neuroradiologic Images and a Review of the Literature,"An 89-year-old woman with chronic atrial fibrillation, hypertension, chronic heart failure, and dementia was admitted to our hospital due to multiple small cerebral and cerebellar infarctions. Transthoracic echocardiogram revealed a floating calcified mass lesion arising from the endocardium of the posterior portion of the mitral annulus with mitral annular calcification. Furthermore, the mass had a heterogeneity of the echogenicity. The mass was diagnosed as a calcified amorphous tumor based on specific echocardiographic features. Serial echocardiograms showed shrinkage and disappearance of the mass, and magnetic resonance image revealed new infarction in the left occipital lobe. Embolization of the mass appeared to cause systemic embolism.",gentamicin;sultamicillin;warfarin;aged;apathy;article;bacterial endocarditis;blood culture;brain embolism;brain infarction;calcified amorphous tumor;case report;cerebellum infarction;cerebrovascular disease;chronic atrial fibrillation;dementia;drug withdrawal;endocardium;fatigue;female;heart failure;heart tumor;human;hypertension;mitral annular calcification;mitral valve;mitral valve disease;nuclear magnetic resonance;nuclear magnetic resonance imaging;occipital lobe;priority journal;short term memory;transesophageal echocardiography;transthoracic echocardiography;tumor calcinosis;tumor embolism;very elderly;whole body CT,"Singu, T.;Inatomi, Y.;Yonehara, T.;Ando, Y.",2017,,10.1016/j.jstrokecerebrovasdis.2017.02.019,0,1224
1224,Calcified Amorphous Tumor Causing Shower Embolism to the Brain: A Case Report with Serial Echocardiographic and Neuroradiologic Images and a Review of the Literature,"An 89-year-old woman with chronic atrial fibrillation, hypertension, chronic heart failure, and dementia was admitted to our hospital due to multiple small cerebral and cerebellar infarctions. Transthoracic echocardiogram revealed a floating calcified mass lesion arising from the endocardium of the posterior portion of the mitral annulus with mitral annular calcification. Furthermore, the mass had a heterogeneity of the echogenicity. The mass was diagnosed as a calcified amorphous tumor based on specific echocardiographic features. Serial echocardiograms showed shrinkage and disappearance of the mass, and magnetic resonance image revealed new infarction in the left occipital lobe. Embolization of the mass appeared to cause systemic embolism.",Embolic stroke;calcified amorphous tumor;mitral annular calcification;shower emboli,"Singu, T.;Inatomi, Y.;Yonehara, T.;Ando, Y.",2017,Mar 15,,0,
1225,The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition causing recurrent subcortical strokes. MR imaging, which shows focal lacunar infarcts and leukoaraiosis, plays a central role in the diagnosis and evaluation. We studied MR imaging abnormalities in a large prospectively recruited cohort of CADASIL patients to describe the spatial distribution of abnormalities, determine how this distribution alters with age, and identify any correlations with the clinical features of the disease. METHODS: In this study, 112 CADASIL subjects from 64 families were prospectively recruited. MR imaging scans were graded by a single neuroradiologist, by using the modified Scheltens scale, to quantify the severity of high-signal-intensity changes in different brain regions. RESULTS: Lesion load increased progressively with age. Scores were maximal in the frontal, parietal, and anterior temporal cortex, and the external capsule; intermediate in the pons; and relatively low in the corpus callosum, caudate, globus pallidus, cerebellum, midbrain, and medulla. Anterior temporal pole involvement was common at all ages and, when present, usually confluent, but this was absent in 33% of patients 20-29 years of age. A history of stroke correlated with total Scheltens score and internal capsule and pontine scores. Dementia correlated with total Scheltens score and subcortical white matter score, whereas depression correlated with subcortical white matter score but not total Scheltens score. CONCLUSIONS: There is a characteristic pattern of MR imaging abnormalities in CADASIL that aids in differential diagnosis; however, some characteristic features, such as anterior temporal pole involvement, can be absent. MR imaging lesion load correlated with some clinical features including stroke and dementia, whereas depression is more common in individuals with deep white matter changes.","Adult;Age Factors;Aged;Aged, 80 and over;CADASIL/complications/genetics/ radiography;Cerebral Cortex/abnormalities/radiography;Disease Progression;Family Health;Female;Genes, Dominant;Humans;Intracranial Arteriosclerosis/complications/pathology/ radiography;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Statistics as Topic;Stroke/etiology/radiography","Singhal, S.;Rich, P.;Markus, H. S.",2005,Nov-Dec,,0,
1226,The influence of genetic and cardiovascular risk factors on the CADASIL phenotype,"The clinical phenotype in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), an autosomal dominant cerebral arteriopathy, is variable, but the reasons for this remain uncertain. Possible factors include the mutation site and the influence of additional modulating factors, which could include both epistatic interactions and interactions with cardiovascular risk factors known to cause sporadic small vessel disease. In a large prospectively recruited cohort of CADASIL subjects we determined relationships between phenotype and mutation site, the apoE genotype and cardiovascular risk factors. In addition to clinical features, disease severity was assessed by MRI lesion volume, measured both semiquantitatively (Scheltens scale) and quantitatively. One hundred and twenty-seven CADASIL cases from 65 families with 17 different mutations were studied. Site of mutation was not associated with the presence or age of onset of stroke, migraine, dementia, dependency or MRI lesion load. There was no evidence of intrafamilial clustering of particular phenotypes. Amongst subjects with stroke/transient ischaemic attack, smoking at the time of the event was independently associated with earlier age of onset (P = 0.01). There were no associations between age of onset or presence of stroke and other cardiovascular risk factors, including homocysteine. Homocysteine levels were higher in migraineurs [mean (SD) 12.8 (5.6) versus 9.8 (3.4) μmol/l, P = 0.02)] and elevated homocysteine was independently associated with an earlier age of onset of migraine (P = 0.01). No relationship was found between MRI lesion volume and risk factors, or between apoE genotype and phenotype. Our results show no notch 3 genotype-phenotype correlations. This implies that modulating factors influence phenotype. Smoking appears to increase the risk of stroke, while high homocysteine levels are associated with an increased risk of migraine.",apolipoprotein E4;cholesterol;homocysteine;adult;article;autosomal dominant disorder;brain infarction;CADASIL;cardiovascular disease;cholesterol blood level;smoking;dementia;diabetes mellitus;female;gene mutation;genotype;human;hypercholesterolemia;hyperhomocysteinemia;hypertension;leukoencephalopathy;major clinical study;male;migraine;nuclear magnetic resonance imaging;onset age;phenotype;priority journal;prospective study;rating scale;risk factor;Scheltens scale;scoring system;cerebrovascular accident,"Singhal, S.;Bevan, S.;Barrick, T.;Rich, P.;Markus, H. S.",2004,,,0,
1227,Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy: A rare syndrome raising anesthetic concerns!,,fentanyl;glycopyrronium bromide;isoflurane;nitrous oxide;oxygen;propofol;rocuronium;adult;anamnesis;anesthesia induction;behavior change;brain biopsy;CADASIL;case report;endotracheal intubation;general anesthesia;human;letter;male;mental deficiency;neurologic examination;nuclear magnetic resonance imaging;personality;premedication;seizure,"Singh, G. P.;Mahajan, C.;Prabhakar, H.;Bindra, A.",2011,,,0,
1228,Is the clinical expression of late-life depression influenced by brain changes? MRI subcortical neuroanatomical correlates of depressive symptoms,"BACKGROUND: ""Vascular depression"" has recently been proposed. It is characterized by magnetic resonance imaging (MRI) T2-weighted subcortical lesions, a late onset of first episode of depression, and reduced heritability; a cerebrovascular etiology is suggested. The validity of ""vascular depression"" might be strengthened if an association was found between the subcortical lesions used to define it and particular depressive symptoms. METHODS: A blinded cross-sectional examination of DSM-III-R depressive symptoms (American Psychiatric Association, 1987) and MRI T2-weighted subcortical lesions in 44 patients with late-life depression. RESULTS: Many associations were found; however, because of multiple comparisons, their significance is viewed with caution. The most robust finding was that psychomotor retardation was independently related to total white-matter score. The odds of showing psychomotor retardation was increased 1.9 times for every point increase in severity of white-matter change. CONCLUSION: In late-life depression the clinical expression of the depression is influenced by the pattern of MRI T2-weighted subcortical lesions. This gives some validity to the concept of an MRI-defined ""vascular"" subtype of late-life depression and strengthens the argument for including neuroimaging in the classification of late-life depression.","Aged;Aged, 80 and over;Brain/ pathology/physiopathology;Dementia, Vascular/pathology/ psychology;Depressive Disorder, Major/classification/ pathology/physiopathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Models, Neurological;Severity of Illness Index","Simpson, S.;Baldwin, R. C.;Jackson, A.;Burns, A.;Thomas, P.",2000,Dec,,0,
1229,"Maspardin is mutated in mast syndrome, a complicated form of hereditary spastic paraplegia associated with dementia","Mast syndrome is an autosomal recessive, complicated form of hereditary spastic paraplegia with dementia that is present at high frequency among the Old Order Amish. Subtle childhood abnormalities may be present, but the main features develop in early adulthood. The disease is slowly progressive, and cerebellar and extrapyramidal signs are also found in patients with advanced disease. Patients have a thin corpus callosum and white-matter abnormalities, as seen on magnetic resonance imaging. Using an extensive Amish pedigree, we have mapped the Mast syndrome locus (SPG21) to a small interval of chromosome 15q22.31 that encompasses just three genes. Sequence analysis of the three transcripts revealed that all 14 affected cases were homozygous for a single base-pair insertion (601insA) in the acid-cluster protein of 33 kDa (ACP33) gene. This frameshift results in the premature termination (fs201-212X213) of the encoded product, which is designated ""maspardin"" (Mast syndrome, spastic paraplegia, autosomal recessive with dementia), and has been shown elsewhere to localize to intracellular endosomal/trans-Golgi transportation vesicles and may function in protein transport and sorting.","Adaptor Proteins, Signal Transducing;Adult;Amino Acid Sequence;Base Sequence;Brain/abnormalities/radiography;Carrier Proteins/chemistry/ genetics;Chromosomes, Human, Pair 15/genetics;DNA Mutational Analysis;Dementia/ complications/ genetics/pathology/radiography;Ethnic Groups/genetics;Female;Genes, Recessive/genetics;Haplotypes/genetics;Humans;Lod Score;Magnetic Resonance Imaging;Male;Middle Aged;Models, Molecular;Molecular Sequence Data;Mutation/ genetics;Pedigree;Protein Conformation;Protestantism;Spastic Paraplegia, Hereditary/ complications/ genetics/pathology/radiography;Syndrome","Simpson, M. A.;Cross, H.;Proukakis, C.;Pryde, A.;Hershberger, R.;Chatonnet, A.;Patton, M. A.;Crosby, A. H.",2003,Nov,10.1086/379522,0,
1230,Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways,"Background and Purpose-White matter lesions (WML) in brain aging are linked to dementia and depression. Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms. Methods-WML were identified by MRI and pathology in brains donated to the Medical Research Council Cognitive Function and Ageing Study Cognitive Function and Aging Study. RNA was extracted to compare WML with nonlesional white matter samples from cases with lesions (WM[L]), and from cases with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional pathways were validated for selected genes by quantitative real-time polymerase chain reaction and immunocytochemistry. Results-We identified 8 major pathways in which multiple genes showed altered RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport, metabolism) among 502 genes that were differentially expressed in WML compared to WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes selected to validate this microarray data all showed the expected changes in RNA levels and immunohistochemical expression of protein. Conclusion- WML represent areas with a complex molecular phenotype. From this and previous evidence, WML may arise through tissue ischemia but may also reflect the contribution of additional factors like blood-brain barrier dysfunction. Differential expression of genes in WM[L] compared to WM[C] indicate a ""field effect"" in the seemingly normal surrounding white matter. © 2009 American Heart Association, Inc.",RNA;aged;apoptosis;article;brain damage;cell cycle;cell structure;controlled study;electron transport;female;human;human tissue;immunochemistry;immunoregulation;ion transport;major clinical study;male;medical research;microarray analysis;nuclear magnetic resonance imaging;priority journal;protein degradation;protein expression;real time polymerase chain reaction;white matter,"Simpson, J. E.;Hosny, O.;Wharton, S. B.;Heath, P. R.;Holden, H.;Fernando, M. S.;Matthews, F.;Forster, G.;O'Brien, J. T.;Barber, R.;Kalaria, R. N.;Brayne, C.;Shaw, P. J.;Lewis, C. E.;Ince, P. G.",2009,,,0,
1231,A unique familial leukodystrophy with adult onset dementia and abnormal glycolipid storage: a new lysosomal disease?,"Two adult siblings with early onset dementia are described. At presentation, in their early 30s, they showed poor judgment and disinhibition. A progressive dementia ensued over several years. Brain MRI disclosed diffusely increased T2 signal in the cerebral white matter, suggestive of a leukodystrophy. Numerous lysosomal enzyme assays including leucocyte arylsulphatase A and galactocerebrosidase activities, plasma and fibroblast very long chain fatty acid concentrations, and urinary sulphatide concentrations were normal, as were CSF analyses. A brain biopsy disclosed periodic acid Schiff (PAS) and Sudan black positive material in perivascular macrophages which, by electron microscopy, consisted of stacks of straight or curvilinear paired membranes within angulate lysosomes, indicative of abnormal glycolipid accumulation. The combination of clinical, radiological, biochemical, and pathological features of this degenerative disease is not consistent with that of any of the known leukodystrophies or lysosomal storage disorders. These findings suggest a previously undescribed familial glycolipid storage disorder causing an adult onset leukodystrophy and presenting with behavioural symptoms that mimic a psychiatric disorder.","Adult;Biopsy;Dementia/diagnosis/*genetics/pathology;Diffuse Cerebral Sclerosis of Schilder/diagnosis/*genetics/pathology;Female;Frontal Lobe/pathology;Glycolipids/*metabolism;Humans;Inclusion Bodies/pathology;Lysosomal Storage Diseases/diagnosis/*genetics/pathology;Lysosomes/pathology;Macrophages/pathology;Magnetic Resonance Imaging;Male;Microscopy, Electron;Neurologic Examination;Synaptic Membranes/pathology","Simon, D. K.;Rodriguez, M. L.;Frosch, M. P.;Quackenbush, E. J.;Feske, S. K.;Natowicz, M. R.",1998,Aug,,0,
1232,Change detection and classification in brain MR images using change vector analysis,"The automatic detection of longitudinal changes in brain images is valuable in the assessment of disease evolution and treatment efficacy. Most existing change detection methods that are currently used in clinical research to monitor patients suffering from neurodegenerative diseases--such as Alzheimer's--focus on large-scale brain deformations. However, such patients often have other brain impairments, such as infarcts, white matter lesions and hemorrhages, which are typically overlooked by the deformation-based methods. Other unsupervised change detection algorithms have been proposed to detect tissue intensity changes. The outcome of these methods is typically a binary change map, which identifies changed brain regions. However, understanding what types of changes these regions underwent is likely to provide equally important information about lesion evolution. In this paper, we present an unsupervised 3D change detection method based on Change Vector Analysis. We compute and automatically threshold the Generalized Likelihood Ratio map to obtain a binary change map. Subsequently, we perform histogram-based clustering to classify the change vectors. We obtain a Kappa Index of 0.82 using various types of simulated lesions. The classification error is 2%. Finally, we are able to detect and discriminate both small changes and ventricle expansions in datasets from Mild Cognitive Impairment patients.",,"Simões, R.;Slump, C.",2011,2011,,0,
1233,Automatic segmentation of cerebral white matter hyperintensities using only 3D FLAIR images,"Magnetic Resonance (MR) white matter hyperintensities have been shown to predict an increased risk of developing cognitive decline. However, their actual role in the conversion to dementia is still not fully understood. Automatic segmentation methods can help in the screening and monitoring of Mild Cognitive Impairment patients who take part in large population-based studies. Most existing segmentation approaches use multimodal MR images. However, multiple acquisitions represent a limitation in terms of both patient comfort and computational complexity of the algorithms. In this work, we propose an automatic lesion segmentation method that uses only three-dimensional fluid-attenuation inversion recovery (FLAIR) images. We use a modified context-sensitive Gaussian mixture model to determine voxel class probabilities, followed by correction of FLAIR artifacts. We evaluate the method against the manual segmentation performed by an experienced neuroradiologist and compare the results with other unimodal segmentation approaches. Finally, we apply our method to the segmentation of multiple sclerosis lesions by using a publicly available benchmark dataset. Results show a similar performance to other state-of-the-art multimodal methods, as well as to the human rater. © 2013 Elsevier Inc.",,"Simões, R.;Mönninghoff, C.;Dlugaj, M.;Weimar, C.;Wanke, I.;van Cappellen van Walsum, A. M.;Slump, C.",2013,September,,0,
1234,Brain damage following prophylactic cranial irradiation in lung cancer survivors,"Long-term toxic effects of prophylactic cranial irradiation (PCI) on cognition in small cell lung cancer (SCLC) patients have not yet been well-established. The aim of our study was to examine the cognitive toxic effects together with brain structural changes in a group of long-term SCLC survivors treated with PCI. Eleven SCLC patients, who underwent PCI ≥ 2 years before, were compared with an age and education matched healthy control group. Both groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging. Voxel-based morphometry and Tract-based Spatial Statistics were used to study gray matter density (GMD) and white matter (WM) microstructural changes. Cognitive deterioration was correlated with GMD and Fractional Anisotropy (FA). Finally, we carried out a single-subject analysis in order to evaluate individual structural brain changes. Nearly half of the SCLC met criteria for cognitive impairment, all exhibiting a global worsening of cognitive functioning. Patients showed significant decreases of GMD in basal ganglia bilaterally (putamen and caudate), bilateral thalamus and right insula, together with WM microstructural changes of the entire corpus callosum. Cognitive deterioration scores correlated positively with mean FA values in the corpus callosum. Single-subject analysis revealed that GMD and WM changes were consistently observed in nearly all patients. This study showed neuropsychological deficits together with brain-specific structural differences in long-term SCLC survivors. Our results suggest that PCI therapy, possibly together with platinum-based chemotherapy, was associated to permanent long-term cognitive and structural brain effects in a SCLC population.",,"Simó, M.;Vaquero, L.;Ripollés, P.;Jové, J.;Fuentes, R.;Cardenal, F.;Rodríguez-Fornells, A.;Bruna, J.",2016,1,,0,
1235,Longitudinal brain changes associated with prophylactic cranial irradiation in lung cancer,"Introduction: The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. Methods: Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire was also completed. Results: Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GMover time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. Conclusions: This longitudinal study documents moderate neuropsychological deficits together with notable brainspecific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects.",,"Simó, M.;Vaquero, L.;Ripollés, P.;Gurtubay-Antolin, A.;Jové, J.;Navarro, A.;Cardenal, F.;Bruna, J.;Rodríguez-Fornells, A.",2016,2016,,0,
1236,Tension pneumocephalus: An uncommon cause of altered mental status,"Background: Pneumocephalus is a rare cause of altered mental status in patients presenting to the Emergency Department. Occurring as a result of traumatic or iatrogenic violation of the dura, it can cause significant morbidity and mortality if tension physiology develops whereby air continues to accumulate with no mechanism for escape. Objective: This case report will review the underlying pathophysiology, clinical presentation, diagnosis, and management of tension pneumocephalus. Case Report: We present the case of an 89-year-old man who presented to the Emergency Department with declining mental status 9 h after endoscopic sinus surgery. He was subsequently found to have tension pneumocephalus and underwent emergent burr hole evacuation. Despite resolution of the pneumocephalus, the patient had persistent neurologic deficits related to ischemic infarcts that occurred as a result of the tension physiology and subsequently expired in the hospital. Conclusion: This case illustrates the importance of considering tension pneumocephalus on the differential diagnosis for any patient presenting with altered mental status after surgical or diagnostic procedures with potential to violate the dural space. Copyright © 2013 Elsevier Inc. Printed in the USA. All rights reserved.",aged;article;bleeding;bone;brain infarction;case report;clinical feature;computer assisted tomography;conservative treatment;differential diagnosis;emergency ward;endoscopic sinus surgery;follow up;Glasgow coma scale;headache;human;intensive care unit;liquorrhea;male;mental deterioration;neuroimaging;neurologic disease;nuclear magnetic resonance imaging;pneumocephalus;priority journal;subarachnoid hemorrhage;tension pneumocephalus;treatment response;vomiting,"Simmons, J.;Luks, A. M.",2013,,,0,
1237,Varicella zoster virus vasculopathy: A treatable form of rapidly progressive multi-infarct dementia after 2 years' duration,"We describe an extraordinarily protracted case of varicella zoster virus (VZV) multifocal vasculopathy in a man who presented initially with ischemic optic neuropathy and then suffered 4 episodes of stroke manifesting as multi-infarct dementia over a 2-year period. Brain magnetic resonance imaging (MRI) and angiography (MRA) revealed cortical and subcortical infarctions as well as vasculitic occlusion and stenosis. The patient was treated with corticosteroids and later with cyclophosphamide. More than 2 years after the onset of neurological disease, two cerebrospinal fluid (CSF) examinations revealed the presence of anti-VZV IgG antibody with reduced serum-to-CSF ratios of anti-VZV IgG compared with ratios for total IgG and albumin, indicative of intrathecal synthesis of anti-VZV IgG. After definitive diagnosis, immunosuppressive drugs were discontinued and he was treated with intravenous acyclovir; both mental status and gait improved and no further episodes of neurological dysfunction ensued. The favorable outcome in this patient indicates that VZV vasculopathy can be treated successfully even after 26 months. VZV must be considered as a possible cause of neurological disease in any patient with idiopathic multifocal vasculopathy. © 2012 Elsevier B.V. All rights reserved.",,"Silver, B.;Nagel, M. A.;Mahalingam, R.;Cohrs, R.;Schmid, D. S.;Gilden, D.",2012,15,,0,
1238,Magnetic resonance imaging in five patients with a tumefactive demyelinating lesion in the central nervous system,"Five patients with a tumefactive lesion were clinically followed from 1992 to 1993. Four patients were female; age ranged from 32 to 57 years, the duration of symptoms varied from 3 days to 3 years. Neurological examination disclosed dementia in two patients, aphasia in three, hemiparesis in four, hemihypoaesthesia in three, optical neuritis in two, tetraparesis with sensitive level and neurogenic bladder in one. MRI disclosed lesions with a hypersignal on images assessed at T2 and hyposignal at T1, and gadolinium heterogeneous enhancement; these lesions were located in the: a) temporooccipital region bilaterally and brain stem, b) frontoparietal white matter, c) basal ganglia, bilateral white matter and brain stem, d) left parietal region, e) cervical spinal cord, with enlargement of this region. Cerebral biopsy was performed in three patients; acute and subacute demyelinating disease was diagnosed by histological examination. Two patients had an evolutive diagnosis; exclusion of other pathologies and clinical and radiological improvement after corticotherapy, pointed to an inflammatory disease.",,"Silva, H. C.;Callegaro, D.;Marchiori, P. E.;Scaff, M.;Tsanaclis, A. M.",1999,Dec,,0,
1239,Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET),"BACKGROUND AND PURPOSE: Reperfusion and recanalization have both been used as surrogate markers of clinical outcome in trials of stroke thrombolysis. We aimed to prove that the beneficial impact of recanalization with intravenous tissue plasminogen activator on clinical outcomes is attributable to reperfusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective, randomized, placebo-controlled trial of intravenous tissue plasminogen activator in the 3- to 6-hour window. Reperfusion was defined as >90% reduction in magnetic resonance perfusion-weighted imaging lesion volume and recanalization as improvement of MR angiographic Thrombolysis In Myocardial Infarction grading by > or =2 points from baseline to Day 3 to 5. RESULTS: At Day 3 to 5, reperfusion and recanalization with intravenous tissue plasminogen activator were strongly correlated. Reperfusion was associated with improved clinical outcome independent of whether recanalization occurred. In contrast, recanalization was not associated with clinical outcome when reperfusion was included as a covariate in regression analyses. CONCLUSIONS: Reperfusion is a surrogate marker of clinical outcomes independent of recanalization based on the criteria applied in EPITHET. The impact of recanalization on clinical outcomes was attributable to reperfusion.","Catheterization [methods] [standards];Cerebral Revascularization [methods] [standards];Double-Blind Method;Echo-Planar Imaging [methods] [standards];Fibrinolytic Agents [administration & dosage];Injections, Intravenous;Prospective Studies;Reperfusion [standards];Stroke [drug therapy] [surgery];Thrombolytic Therapy [methods] [standards];Tissue Plasminogen Activator [administration & dosage];Treatment Outcome;Humans[checkword]","Silva, D. A.;Fink, J. N.;Christensen, S.;Ebinger, M.;Bladin, C.;Levi, C. R.;Parsons, M.;Butcher, K.;Barber, P. A.;Donnan, G. A.;Davis, S. M.",2009,,,0,
1240,The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia,"Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia.",,"Silva, B. C.;de Miranda, A. S.;Rodrigues, F. G.;Silveira, A. L.;Resende, G. H.;Moraes, M. F.;de Oliveira, A. C.;Parreiras, P. M.;Barcelos Lda, S.;Teixeira, M. M.;Machado, F. S.;Teixeira, A. L.;Rachid, M. A.",2015,,,0,
1241,"Cortical petechial hemorrhage, leukoencephalopathy, and subacute dementia associated with seizures due to cerebral amyloid angiopathy","Although cerebral amyloid angiopathy is a well-known cause of cerebral lobar hemorrhage, subacute dementia, seizures, and acute encephalopathy without lobar hemorrhage are infrequently recognized as manifestations of this disease. In this report, we describe a case of cerebral amyloid angiopathy in a 74-year-old woman who had subacute progressive dementia and a superimposed rapid acute neurologic deterioration associated with seizures and the presence of cerebral edema on computed tomographic scans and leukoencephalopathy and cortical petechial hemorrhages on magnetic resonance imaging. A diagnosis of cerebral amyloid angiopathy in conjunction with small cortical infarcts and petechial hemorrhages was confirmed by antemortem biopsy. This clinical and radiologic picture is being increasingly recognized as characteristic of cerebral amyloid angiopathy.",,"Silbert, P. L.;Bartleson, J. D.;Miller, G. M.;Parisi, J. E.;Goldman, M. S.;Meyer, F. B.",1995,1995,,0,
1242,Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline,"Background: White matter hyperintensity (WMH) change on brain MRI is observed with increased frequency in the elderly and has been independently associated with neurologic decline. The degree to which the location and rate of volume increase in WMH affects other structural brain changes along with cognitive and motor performance over time may determine subsequent degrees of risk for dementia and other syndromes of aging. Methods: One hundred four cognitively intact men and women followed longitudinally for up to 13 years underwent at least three MRIs with corresponding annual cognitive and neurologic assessments. Brain volume, ventricular CSF (vCSF), and total periventricular (PV) and subcortical WMH volumes were measured. Progression of MRI volumes was examined in relation to rates of cognitive, motor, and cerebral volume change based on slopes of outcomes. Results: Higher initial total and PV WMH volume was associated with total WMH, PV WMH, and vCSF progression, and with increased time and number of steps to walk 30 feet. Progression of PV WMH volume was associated with increased time to walk 30 feet. Progression of subcortical WMH volume was associated with decreased performance on logical memory testing and increased rate of vCSF volume change. Conclusion: Increased total and periventricular (PV) white matter hyperintensity (WMH) burden and progression of PV WMH burden are associated with decreased gait performance over time, while progression of subcortical WMH volume is associated with memory decline in cognitively intact elderly. Greater progression of WMH burden is associated with an increased risk of memory and gait dysfunction, and thus should not be considered a benign process. Copyright © 2008 by AAN Enterprises, Inc.",aged;article;brain cortex;brain size;cerebrospinal fluid analysis;clinical assessment;cognition;female;human;longitudinal study;male;memory;motor performance;normal human;nuclear magnetic resonance imaging;outcome assessment;priority journal;walking;white matter,"Silbert, L. C.;Nelson, C.;Howieson, D. B.;Moore, M. M.;Kaye, J. A.",2008,,,0,
1243,Cortical excitability and age-related volumetric MRI changes,"OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.","Aged;Aged, 80 and over;Aging/*cerebrospinal fluid/*physiology;Brain Mapping;Cerebral Cortex/*anatomy & histology/*physiology;Cerebrovascular Circulation;Differential Threshold;Female;Functional Laterality;G0 Phase;Humans;*Magnetic Resonance Imaging;Male;Sensitivity and Specificity;Transcranial Magnetic Stimulation/methods","Silbert, L. C.;Nelson, C.;Holman, S.;Eaton, R.;Oken, B. S.;Lou, J. S.;Kaye, J. A.",2006,May,10.1016/j.clinph.2006.02.003,0,
1244,Cognitive impairment risk: white matter hyperintensity progression matters,"OBJECTIVE: To determine whether white matter hyperintensity (WMH) progression rate is a better predictor of cognitive impairment risk than baseline WMH volume in healthy elderly individuals. METHOD: Ninety-eight cognitively intact elderly subjects were followed in the Oregon Brain Aging Study. Forty-nine had at least 3 brain MRIs and annual cognitive and neurologic assessments until diagnosed with persistent cognitive impairment (PCI). Brain, ventricular CSF (vCSF), intracranial volume (ICV), hippocampus, total WMH, periventricular (PV) WMH, and subcortical WMH volumes were measured. Cox proportional hazards survival analyses were used to assess cognitive impairment risk. RESULTS: After adjusting for age, apolipoprotein E4 status, incident hypertension, ICV, entry Mini-Mental State Examination, baseline hippocampus, and both baseline vCSF volume and rate of vCSF volume change, increased progression of total WMH volume (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.3-2.7, p = 0.0007) and PV WMH volume (HR 1.94, 95% CI 1.3-3.1, p = 0.001) conferred higher risk of PCI, whereas baseline WMH volumes did not. Every 1 mL/y increase in PV WMH volume was associated with a 94% increased risk of PCI. CONCLUSION: Progression of total and periventricular (PV) white matter hyperintensity (WMH) volumes are better predictors of persistent cognitive impairment (PCI) than baseline WMH burden. Greater PV WMH burden progression is associated with the development of PCI, a potential precursor to Alzheimer or vascular dementia. Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population.","Age Factors;Aged, 80 and over;Apolipoprotein E4/genetics;Brain/*pathology;Cerebral Ventricles/pathology;Cognition Disorders/*diagnosis/genetics/*pathology;Female;Follow-Up Studies;Hippocampus/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;*Nerve Fibers, Myelinated;Organ Size;Proportional Hazards Models;Risk Factors","Silbert, L. C.;Howieson, D. B.;Dodge, H.;Kaye, J. A.",2009,Jul 14,10.1212/WNL.0b013e3181ad53fd,0,
1245,Trajectory of white matter hyperintensity burden preceding mild cognitive impairment,"OBJECTIVE: To determine the time of acceleration in white matter hyperintensity (WMH) burden, a common indicator of cerebrovascular pathology, in relation to conversion to mild cognitive impairment (MCI) in the elderly. METHODS: A total of 181 cognitively intact elderly volunteers from the longitudinal, prospective, Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MRIs were analyzed for imaging markers of neurodegeneration: WMH and ventricular CSF (vCSF) volumes. The time before MCI, when the changes in WMH and vCSF burden accelerate, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow-up. RESULTS: During a follow-up duration of up to 19.6 years, 134 subjects converted to MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %vCSF volume increase occurred 3.7 years before the onset of MCI. Out of 63 subjects who converted to MCI and had autopsy, only 28.5% had Alzheimer disease (AD) as the sole etiology of their dementia, while almost just as many (24%) had both AD and significant ischemic cerebrovascular disease present. CONCLUSIONS: Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathologic change that emerges early in the presymptomatic phase leading to MCI. Longitudinal changes in WMH may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease-modifying therapies prior to dementia onset.","Aged;Aged, 80 and over;Brain/pathology;Cerebrospinal Fluid/metabolism;Disease Progression;Early Diagnosis;Female;Geriatric Assessment/methods;Humans;Magnetic Resonance Imaging/methods;Male;Mild Cognitive Impairment/cerebrospinal fluid/diagnosis/ pathology;Nerve Fibers, Myelinated/ pathology;Neuroimaging/methods;Time Factors","Silbert, L. C.;Dodge, H. H.;Perkins, L. G.;Sherbakov, L.;Lahna, D.;Erten-Lyons, D.;Woltjer, R.;Shinto, L.;Kaye, J. A.",2012,Aug 21,10.1212/WNL.0b013e3182661f2b,0,
1246,Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly,"BACKGROUND: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. OBJECTIVE: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. METHODS: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. RESULTS: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. CONCLUSIONS: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.","Activities of Daily Living;Aged;Aged, 80 and over;Aging/ pathology;Computers;Female;Frontal Lobe/diagnostic imaging/pathology;Gray Matter/diagnostic imaging/pathology;Hippocampus/ diagnostic imaging/ pathology;Humans;Image Processing, Computer-Assisted;Linear Models;Magnetic Resonance Imaging;Male;Multivariate Analysis;Organ Size;Temporal Lobe/diagnostic imaging/pathology;White Matter/diagnostic imaging/pathology;Alzheimer's disease;Mri;assessment of cognitive disorders/dementia;cognitive aging;volumetric MRI","Silbert, L. C.;Dodge, H. H.;Lahna, D.;Promjunyakul, N. O.;Austin, D.;Mattek, N.;Erten-Lyons, D.;Kaye, J. A.",2016,,,0,1247
1247,Less Daily Computer Use is Related to Smaller Hippocampal Volumes in Cognitively Intact Elderly,"BACKGROUND: Computer use is becoming a common activity in the daily life of older individuals and declines over time in those with mild cognitive impairment (MCI). The relationship between daily computer use (DCU) and imaging markers of neurodegeneration is unknown. OBJECTIVE: The objective of this study was to examine the relationship between average DCU and volumetric markers of neurodegeneration on brain MRI. METHODS: Cognitively intact volunteers enrolled in the Intelligent Systems for Assessing Aging Change study underwent MRI. Total in-home computer use per day was calculated using mouse movement detection and averaged over a one-month period surrounding the MRI. Spearman's rank order correlation (univariate analysis) and linear regression models (multivariate analysis) examined hippocampal, gray matter (GM), white matter hyperintensity (WMH), and ventricular cerebral spinal fluid (vCSF) volumes in relation to DCU. A voxel-based morphometry analysis identified relationships between regional GM density and DCU. RESULTS: Twenty-seven cognitively intact participants used their computer for 51.3 minutes per day on average. Less DCU was associated with smaller hippocampal volumes (r = 0.48, p = 0.01), but not total GM, WMH, or vCSF volumes. After adjusting for age, education, and gender, less DCU remained associated with smaller hippocampal volume (p = 0.01). Voxel-wise analysis demonstrated that less daily computer use was associated with decreased GM density in the bilateral hippocampi and temporal lobes. CONCLUSIONS: Less daily computer use is associated with smaller brain volume in regions that are integral to memory function and known to be involved early with Alzheimer's pathology and conversion to dementia. Continuous monitoring of daily computer use may detect signs of preclinical neurodegeneration in older individuals at risk for dementia.",,"Silbert, L. C.;Dodge, H. H.;Lahna, D.;Promjunyakul, N. O.;Austin, D.;Mattek, N.;Erten-Lyons, D.;Kaye, J. A.",2016,Mar 9,10.3233/jad-160079,0,
1248,"Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study)","BACKGROUND AND PURPOSE: The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. METHODS: Participants (n=2612, 41% men, mean age 74.6+/-4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. RESULTS: Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). CONCLUSIONS: Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.","Aged;Aged, 80 and over;Brain Infarction/diagnostic imaging/ epidemiology;Cerebellum/blood supply/diagnostic imaging;Cerebral Cortex/blood supply/diagnostic imaging;Cognitive Dysfunction/ epidemiology;Dementia/ epidemiology;Female;Humans;Iceland/epidemiology;Incidence;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;cognition;cohort studies;dementia;risk","Sigurdsson, S.;Aspelund, T.;Kjartansson, O.;Gudmundsson, E. F.;Jonsdottir, M. K.;Eiriksdottir, G.;Jonsson, P. V.;van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2017,Sep,,0,
1249,Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study,"Imaging studies have reported conflicting findings on how brain structure differs with age and sex. This may be explained by discrepancies and limitations in study population and study design. We report a study on brain tissue volumes in one of the largest cohorts of individuals studied to date of subjects with high mean age (mean +/- standard deviation (SD) 76 +/- 6 years). These analyses are based on magnetic resonance imaging (MRI) scans acquired at baseline on 4303 non-demented elderly, and 367 who had a second MRI, on average 2.5 +/- 0.2 years later. Tissue segmentation was performed with an automatic image analysis pipeline. Total brain parenchymal (TBP) volume decreased with increasing age while there was an increase in white matter hyperintensities (WMH) in both sexes. A reduction in both normal white matter (NWM)- and gray matter (GM) volume contributed to the brain shrinkage. After adjusting for intra-cranial volume, women had larger brain volumes compared to men (3.32%, p < 0.001) for TBP volume in the cross-sectional analysis. The longitudinal analysis showed a significant age-sex interaction in TBP volume with a greater rate of annual change in men (-0.70%, 95%CI: -0.78% to -0.63%) than women (-0.55%, 95%CI: -0.61% to -0.49%). The annual change in the cross-sectional data was approximately 40% less than the annual change in the longitudinal data and did not show significant age-sex interaction. The findings indicate that the cross-sectional data underestimate the rate of change in tissue volumes with age as the longitudinal data show greater rate of change in tissue volumes with age for all tissues.","Age Factors;Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Organ Size","Sigurdsson, S.;Aspelund, T.;Forsberg, L.;Fredriksson, J.;Kjartansson, O.;Oskarsdottir, B.;Jonsson, P. V.;Eiriksdottir, G.;Harris, T. B.;Zijdenbos, A.;van Buchem, M. A.;Launer, L. J.;Gudnason, V.",2012,Feb 15,10.1016/j.neuroimage.2011.11.024,0,
1250,Regional myo-inositol concentration in mild cognitive impairment Using 1H magnetic resonance spectroscopic imaging,"The goal was to assess regional patterns of metabolite abnormalities in mild cognitive impairment (MCI) and Alzheimer disease (AD) patients using proton magnetic resonance spectroscopy imaging at 1.5 Tesla. Fourteen MCI, 17 AD, and 16 healthy control (HC) subjects were studied. MCI was associated with higher myo-inositol (mIn) concentration in right parietal white matter compared with HC and lower mIn levels in frontal white matter compared with AD. AD was associated with higher mIn concentration in frontal and parietal white matter compared with HC. N-acetylaspartate (NAA) concentration of white matter was similar in all groups, whereas NAA concentration of gray matter showed a trend toward lower values in the right parietal lobe in AD compared with MCI and HC. A mIn increase in white matter in absence of significant NAA reduction suggests that mIn is a more robust and sensitive marker of white matter pathology in AD and MCI than NAA. Furthermore, the dissociation between mIn and NAA alterations in white matter could provide important information regarding the role of glial and neuronal damage in MCI and AD.",Aged;Alzheimer Disease/ metabolism;Brain/ metabolism;Cognition Disorders/ metabolism;Female;Humans;Inositol/ metabolism;Magnetic Resonance Spectroscopy;Male,"Siger, M.;Schuff, N.;Zhu, X.;Miller, B. L.;Weiner, M. W.",2009,Jan-Mar,10.1097/WAD.0b013e3181875434,0,
1251,Clinical presentation and patterns of regional cerebral atrophy related to the length of trinucleotide repeat expansion in patients with adult onset Huntington's disease,"We correlated trinucleotide CAG repeat numbers in the huntingtin gene with the regional brain atrophy and clinical phenotype in 23 adult autopsy cases of Huntington's disease (HD). CAG repeat number (39-56, mean 45.4 +/- 4.6) correlated inversely (P < 0.0001) with age at onset and death, but not with disease duration or initial symptoms. Cross-sectional areas of the striatum, pallidum, thalamus, amygdala, hippocampus, and the cortical grey and white matter within the frontal, temporal and parietal lobes at four levels (genu of the corpus callosum, amygdala, accumbens, hippocampus) were measured morphometrically from the coronal brain slices using image analysis. None of these morphometric variables correlated with number of CAG repeats. Thus, tissue atrophy in advanced HD is unrelated to the underlying genetic defect.","Adolescent;Adult;Age of Onset;Atrophy/genetics;Brain/ pathology;Female;Genotype;Humans;Huntington Disease/genetics/ pathology;In Vitro Techniques;Linear Models;Male;Middle Aged;Oligonucleotides/ genetics;Phenotype;Repetitive Sequences, Nucleic Acid","Sieradzan, K.;Mann, D. M.;Dodge, A.",1997,Mar 28,,0,
1252,Cerebral blood flow in white matter is correlated with systolic blood pressure and EEG in senile dementia of the Alzheimer type,"The presence and functional significance of white matter lesions in the ageing brain and in dementia as well as their relation to blood pressure are often discussed. The aim of this study was to evaluate cerebral blood flow in white matter (WMCBF) and its relation to systemic blood pressure and multichannel EEG. WMCBF was measured in 24 elderly women with senile dementia of Alzheimer's type (SDAT, median age 85.5, range 68-93) and 20 age-matched controls (median age 86.0, range 79-93) using 99mTc-HMPAO single photon emission CT. A significant low WMCBF could be observed in all analysed regions in SDAT subjects compared to controls, with the greatest decline in the posterior region (parietotemporo-occipital area). Correlations between quantified EEG from the posterior regions and WMCBF were seen. Systolic blood pressure was significantly lower in the SDAT group and was positively correlated with WMCBF in the posterior and anterior brain regions. Whether low systemic blood pressure is the result of crerebral dysfunction is unclear.","Aged;Aged, 80 and over;Alzheimer Disease/*physiopathology/radionuclide imaging;Blood Pressure/*physiology;Cerebrovascular Circulation/*physiology;*Electroencephalography;Female;Humans;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Siennicki-Lantz, A.;Lilja, B.;Rosen, I.;Elmstahl, S.",1998,Jan-Feb,,0,
1253,Magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases,"Human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. There are no useful biomarkers of disease progression. Cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. We investigated the cross-sectional, longitudinal and post-mortem cerebral magnetization transfer ratios as a surrogate for prion disease pathology. Twenty-three prion disease patients with various prion protein gene mutations and 16 controls underwent magnetization transfer ratio and conventional magnetic resonance imaging at 1.5 T. For each subject, whole-brain, white and grey matter magnetization transfer ratio histogram mean, peak height, peak location, and magnetization transfer ratio at 25th, 50th and 75th percentile were computed and correlated with several cognitive, functional and neuropsychological scales. Highly significant associations were found between whole brain magnetization transfer ratio and prion disease (P < 0.01). Additionally, highly significant correlations were found between magnetization transfer ratio histogram parameters and clinical, functional and neuropsychological scores (P < 0.01). Longitudinally, decline in the Clinician's Dementia Rating scale was correlated with decline in magnetization transfer ratio. To investigate the histological correlates of magnetization transfer ratio, formalin-fixed cerebral and cerebellar hemispheres from 19 patients and six controls underwent magnetization transfer ratio imaging at 1.5 T, with mean magnetization transfer ratio calculated from six regions of interest, and findings were followed-up in six variant Creutzfeldt-Jakob disease cases with 9.4 T high-resolution magnetization transfer imaging on frontal cortex blocks, with semi-quantitative histopathological scoring of spongiosis, astrocytosis and prion protein deposition. Post-mortem magnetization transfer ratios was significantly lower in patients than controls in multiple cortical and subcortical regions, but not frontal white matter. Measurements (9.4 T) revealed a significant and specific negative correlation between cortical magnetization transfer ratios and spongiosis (P = 0.02), but not prion protein deposition or gliosis. The magnetic resonance imaging measurement of magnetization transfer ratios may be an in vivo surrogate for spongiform change and has potential utility as a therapeutic biomarker in human prion disease.","Adult;Brain/ pathology/physiopathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Prion Diseases/ pathology/physiopathology;Severity of Illness Index;Statistics, Nonparametric","Siddique, D.;Hyare, H.;Wroe, S.;Webb, T.;Macfarlane, R.;Rudge, P.;Collinge, J.;Powell, C.;Brandner, S.;So, P. W.;Walker, S.;Mead, S.;Yousry, T.;Thornton, J. S.",2010,Oct,10.1093/brain/awq243,0,
1254,Acute EEG findings in HIV-infected Zambian adults with new-onset seizure,"OBJECTIVE: To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure. METHODS: Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome. RESULTS: Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103-560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051). CONCLUSIONS: EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis.",AIDS Dementia Complex/ complications/mortality/pathology/ physiopathology;Adolescent;Adult;Brain/pathology/ physiopathology;Brain Waves;Cognition/physiology;Electroencephalography;Female;Humans;Magnetic Resonance Imaging;Male;Neuroimaging;Neuropsychological Tests;Recurrence;Seizures/ complications/mortality/pathology/ physiopathology;White Matter/pathology;Young Adult;Zambia,"Siddiqi, O. K.;Elafros, M. A.;Sikazwe, I.;Birbeck, G. L.;Kalungwana, L.;Potchen, M. J.;Bositis, C. M.;Koralnik, I. J.;Theodore, W. H.",2015,Mar 31,10.1212/wnl.0000000000001411,0,
1255,White matter lesions are associated with hospital admissions because of hip-fractures and trauma after ischemic stroke,"BACKGROUND AND PURPOSE -: Cerebral white matter lesions (WMLs), a surrogate for cerebral small-vessel disease, have been shown to be associated with decreasing mobility, gait instability, and falls. The aim of this study was to investigate whether WMLs of the brain are associated with increased incidence of hospital admissions because of any trauma and hip-fractures in a cohort of patients with stroke. METHODS -: We included 383 consecutive patients aged 55 to 85 years with ischemic stroke admitted to the Helsinki University Central Hospital (The Stroke Aging Memory cohort) with a 12-year follow-up. National register data were reviewed for hip-fractures, other traumatic injuries, survival data, and causes of death. WMLs were rated using MRI and dichotomized as none to mild and moderate to severe. The data were analyzed using Kaplan-Meier plots (log-rank) and a complex Cox multivariable hazards models for multiple cases per subject to assess hazard ratios with their 95% confidence intervals. RESULTS -: During the 12-year follow-up, there were more hip-fractures (13.5% versus 6.5%; log-rank, P=0.01) and more hospital admissions because of traumatic injury (22.2% versus 16.7%; log-rank, P=0.04) in the moderate-to-severe than in the none-to-mild WMLs group. In the complex samples, Cox multivariable model adjusting for age, sex, National Institutes of Health Stroke Scale, infarct size, and poststroke dementia, moderate-to-severe WMLs were associated with increased incidences of hospital admissions because of hip-fractures (hazard ratio, 3.98; 95% confidence interval, 1.55-10.21) and traumatic injuries including hip-fractures (hazard ratio, 1.72; 95% confidence interval, 1.03-2.87). CONCLUSIONS -: Patients with ischemic stroke and moderate-to-severe WMLs are at high risk, who experience serious traumatic injuries and especially hip-fractures requiring hospital treatment.",adult;aged;article;brain ischemia;dementia;disease association;female;follow up;hazard ratio;hip fracture;hip injury;hospital admission;human;injury;major clinical study;male;National Institutes of Health Stroke Scale;priority journal;survival;white matter lesion,"Sibolt, G.;Curtze, S.;Melkas, S.;Pohjasvaara, T.;Kaste, M.;Karhunen, P. J.;Oksala, N. K. J.;Strandberg, T.;Erkinjuntti, T.",2014,,10.1161/strokeaha.114.006116,0,1256
1256,White matter lesions are associated with hospital admissions because of hip-fractures and trauma after ischemic stroke,"BACKGROUND AND PURPOSE: Cerebral white matter lesions (WMLs), a surrogate for cerebral small-vessel disease, have been shown to be associated with decreasing mobility, gait instability, and falls. The aim of this study was to investigate whether WMLs of the brain are associated with increased incidence of hospital admissions because of any trauma and hip-fractures in a cohort of patients with stroke. METHODS: We included 383 consecutive patients aged 55 to 85 years with ischemic stroke admitted to the Helsinki University Central Hospital (The Stroke Aging Memory cohort) with a 12-year follow-up. National register data were reviewed for hip-fractures, other traumatic injuries, survival data, and causes of death. WMLs were rated using MRI and dichotomized as none to mild and moderate to severe. The data were analyzed using Kaplan-Meier plots (log-rank) and a complex Cox multivariable hazards models for multiple cases per subject to assess hazard ratios with their 95% confidence intervals. RESULTS: During the 12-year follow-up, there were more hip-fractures (13.5% versus 6.5%; log-rank, P=0.01) and more hospital admissions because of traumatic injury (22.2% versus 16.7%; log-rank, P=0.04) in the moderate-to-severe than in the none-to-mild WMLs group. In the complex samples, Cox multivariable model adjusting for age, sex, National Institutes of Health Stroke Scale, infarct size, and poststroke dementia, moderate-to-severe WMLs were associated with increased incidences of hospital admissions because of hip-fractures (hazard ratio, 3.98; 95% confidence interval, 1.55-10.21) and traumatic injuries including hip-fractures (hazard ratio, 1.72; 95% confidence interval, 1.03-2.87). CONCLUSIONS: Patients with ischemic stroke and moderate-to-severe WMLs are at high risk, who experience serious traumatic injuries and especially hip-fractures requiring hospital treatment.",hospital admission;human;hip fracture;injury;brain ischemia;white matter lesion;confidence interval;hazard ratio;patient;model;follow up;cerebrovascular accident;hospital;white matter;gait;dementia;infarction;National Institutes of Health Stroke Scale;cerebrovascular disease;brain;hazard;death;survival;register;memory;aging;risk;university;nuclear magnetic resonance imaging,"Sibolt, G.;Curtze, S.;Melkas, S.;Pohjasvaara, T.;Kaste, M.;Karhunen, P. J.;Oksala, N. K. J.;Strandberg, T.;Erkinjuntti, T.",2014,,,0,
1257,The role of diffusion tensor imaging and fractional anisotropy in the evaluation of patients with idiopathic normal pressure hydrocephalus: a literature review,"OBJECTIVE Diffusion tensor imaging (DTI) for the assessment of fractional anisotropy (FA) and involving measurements of mean diffusivity (MD) and apparent diffusion coefficient (ADC) represents a novel, MRI-based, noninvasive technique that may delineate microstructural changes in cerebral white matter (WM). For example, DTI may be used for the diagnosis and differentiation of idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative diseases with similar imaging findings and clinical symptoms and signs. The goal of the current study was to identify and analyze recently published series on the use of DTI as a diagnostic tool. Moreover, the authors also explored the utility of DTI in identifying patients with iNPH who could be managed by surgical intervention. METHODS The authors performed a literature search of the PubMed database by using any possible combinations of the following terms: ""Alzheimer's disease,"" ""brain,"" ""cerebrospinal fluid,"" ""CSF,"" ""diffusion tensor imaging,"" ""DTI,"" ""hydrocephalus,"" ""idiopathic,"" ""magnetic resonance imaging,"" ""normal pressure,"" ""Parkinson's disease,"" and ""shunting."" Moreover, all reference lists from the retrieved articles were reviewed to identify any additional pertinent articles. RESULTS The literature search retrieved 19 studies in which DTI was used for the identification and differentiation of iNPH from other neurodegenerative diseases. The DTI protocols involved different approaches, such as region of interest (ROI) methods, tract-based spatial statistics, voxel-based analysis, and delta-ADC analysis. The most studied anatomical regions were the periventricular WM areas, such as the internal capsule (IC), the corticospinal tract (CST), and the corpus callosum (CC). Patients with iNPH had significantly higher MD in the periventricular WM areas of the CST and the CC than had healthy controls. In addition, FA and ADCs were significantly higher in the CST of iNPH patients than in any other patients with other neurodegenerative diseases. Gait abnormalities of iNPH patients were statistically significantly and negatively correlated with FA in the CST and the minor forceps. Fractional anisotropy had a sensitivity of 94% and a specificity of 80% for diagnosing iNPH. Furthermore, FA and MD values in the CST, the IC, the anterior thalamic region, the fornix, and the hippocampus regions could help differentiate iNPH from Alzheimer or Parkinson disease. Interestingly, CSF drainage or ventriculoperitoneal shunting significantly modified FA and ADCs in iNPH patients whose condition clinically responded to these maneuvers. CONCLUSIONS Measurements of FA and MD significantly contribute to the detection of axonal loss and gliosis in the periventricular WM areas in patients with iNPH. Diffusion tensor imaging may also represent a valuable noninvasive method for differentiating iNPH from other neurodegenerative diseases. Moreover, DTI can detect dynamic changes in the WM tracts after lumbar drainage or shunting procedures and could help identify iNPH patients who may benefit from surgical intervention.",AD = Alzheimer disease;ADC = apparent diffusion coefficient;Alzheimer disease;CC = corpus callosum;CST = corticospinal tract;DKI = diffusional kurtosis imaging;DTI = diffusion tensor imaging;FA = fractional anisotropy;IC = internal capsule;MD = mean diffusivity;MTR = magnetization transfer ratio;NPH = normal pressure hydrocephalus;PD = Parkinson disease;Parkinson disease;ROI = region of interest;TBSS = tract-based spatial statistics;WM = white matter;diffusion tensor imaging;fractional anisotropy;iNPH = idiopathic NPH;idiopathic;normal pressure hydrocephalus;vascular disorders,"Siasios, I.;Kapsalaki, E. Z.;Fountas, K. N.;Fotiadou, A.;Dorsch, A.;Vakharia, K.;Pollina, J.;Dimopoulos, V.",2016,Sep,10.3171/2016.6.focus16192,0,
1258,"Vascular dementia of binswanger's type: Clinical, neuroradiological and 99mTc-HMPAO SPET study","In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n = 11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n = 13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.",hexamethylpropylene amine oxime technetium tc 99m;adult;aged;article;Binswanger encephalopathy;brain atrophy;brain blood flow;brain perfusion;brain tomography;clinical article;clinical feature;cognitive defect;computer assisted tomography;controlled study;densitometry;disease severity;female;frontal lobe;human;male;multiinfarct dementia;neuroradiology;parenchyma;single photon emission computer tomography;white matter,"Shyu, W. C.;Lin, J. C.;Shen, C. C.;Hsu, Y. D.;Lee, C. C.;Shiah, I. S.;Tsao, W. L.",1996,,,0,
1259,Panencephalitic Creutzfeldt-Jakob disease. Unusual presentation of magnetic resonance imaging and proton magnetic resonance spectroscopy,"We present serial magnetic resonance imaging (MRI) scans on a biopsy-verified case of Creutzfeldt-Jakob disease (CJD). The initial MRI scan demonstrated increased T2 signal-intensity within the basal ganglia and thalami. Subsequent MRI scans demonstrated a thin cortex, increased T2 signals diffusely within the white matter including U-fibers, and hypointense T2 signals within the basal ganglia, and thalami. Proton magnetic resonance spectroscopy ((1)H-MRS) study showed an absence of creatine, choline and N-acetylaspartate signals. By these characteristic findings, serial MRI and MRS studies may be helpful in differentiating CJD from other dementing illnesses.",,"Shyu, W. C.;Lee, C. C.;Hsu, Y. D.;Lin, J. C.;Lee, J. T.;Lee, W. H.;Tsao, W. L.",1996,1996,,0,
1260,Panencephalitic Creutzfeldt-Jakob disease in a chinese family unusual presentation with PrP codon 210 mutation and identification by PCR-SSCP,"A point mutation at codon 210 (GTT to ATT) of the prion protein gene on chromosome 20 was found in a 48-year-old CJD-affected woman of a Chinese family. This affected woman had an early onset and long-duration form of CJD. Serial magnetic resonance image (MRI) analysis of this woman showed severe brain atrophy, prominent diffuse white matter degeneration, and subsequent mineralization of basal ganglia and thalamus. MR spectroscopy ((1)H) analysis elucidated the absence of peaks of choline, creatine and N-acetylaspartate. Using polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) techniques, presymptomatic diagnosis of the second son of this woman showed that he has a similar codon mutation of prion gene as his mother.",,"Shyu, W. C.;Hsu, Y. D.;Kao, M. C.;Tsao, W. L.",1996,November,,0,
1261,Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus,"Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy controls. When evaluating by subgroups, no correlation was found between patients with or without neuropsychiatric systemic lupus erythematosus or cognitive impairment and retinal nerve fiber layer thickness. Conclusion Retinal nerve fiber layer thickness of systemic lupus erythematosus patients was not found to be statistically different compared to controls. Within systemic lupus erythematosus patients there was no correlation between retinal nerve fiber layer thickness and cognitive impairment or other neuropsychiatric systemic lupus erythematosus manifestations.",Neuropsychiatric lupus;antiphospholipid syndrome;systemic lupus erythematosus,"Shulman, S.;Shorer, R.;Wollman, J.;Dotan, G.;Paran, D.",2017,Nov,,0,
1262,"CADASIL Disease, an Inherited Slowly Progressive Vascular Dementia: Case Report with Radiologic and Electron Microscopic Findings","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) disease, a genetically determined arteriopathy, is a rare cause of vascular dementia. We present a case report of a 50-year-old man with migraines associated with left-sided weakness since age 34 years, a stroke at age 43 years, followed by progressive dementia. Magnetic resonance imaging revealed diffuse leukoencephalopathy with involvement of bilateral anterior temporal lobes. Skin biopsy was performed because of clinical suggestion of CADASIL and positive family history. Electron microscopy revealed granular osmophilic material deposits in dermal arterioles, diagnostic for CADASIL disease. A brief discussion of reasons for false-negative skin biopsy findings, differential diagnosis, and treatment of patients with CADASIL disease is presented. © 2009 National Stroke Association.",,"Shuja, S.;Lindquist, J.;Lee, K. P.;Silliman, S.;Makary, R.",2009,November,,0,
1263,Voxel-based diffusion tensor imaging of an APP/PS1 mouse model of Alzheimer's disease,"Increasing evidence has demonstrated that white matter (WM) disruptions, due to the injury of the axon and myelin, play an important role in the pathogenesis of Alzheimer's disease (AD). Diffusion tensor imaging (DTI) is a sensitive modality to evaluate the WM integrity in both AD patients and animal models. In this study, an advanced DTI modality, employing a 7.0-T magnetic resonance imaging system, was used to analyze WM changes across the whole brain of an amyloid precursor protein/presenilin 1 (APP/PS1) mouse model. A voxel-based analysis was used to compare the quantitative DTI parameters automatically in both APP/PS1 mice (n = 9) and wild-type (WT) controls (n = 9). After DTI examination, the ultrastructure analysis was compared with DTI findings. Compared with WT controls, gray matter (GM) areas in APP/PS1 mice such as the cingulate cortex and the striatum showed significant fractional anisotropy (FA) and axial diffusivity (DA) increase, while the thalamus only showed a significant FA increase (p < 0.01). Similarly, a significant mean diffusivity, DA, and radial diffusivity increase was observed in the bilateral neocortex (p < 0.01). The left hippocampus only showed significant FA increase in APP/PS1 mice (p < 0.01). The changes in WM regions were detected in the forceps minor of the corpus callosum, the anterior part of the anterior commissure, and the internal capsule, with a significant FA or DA increase (p < 0.01). Abnormalities derived from diffusion measurements were in-line with the ultrastructure findings, including extensive pathological damage of the neurons, neutrophils, and vessels. In conclusion, voxel-based diffusion tensor imaging can detect diffusion alterations not only in GM but also in WM areas in AD models, reflecting the extensive pathological changes of AD.","Alzheimer Disease/ pathology;Amyloid beta-Protein Precursor/ metabolism;Animals;Anisotropy;Diffusion Tensor Imaging;Disease Models, Animal;Hippocampus/pathology/ultrastructure;Mice;Mice, Transgenic;Neocortex/pathology/ultrastructure;Presenilin-1/ metabolism","Shu, X.;Qin, Y. Y.;Zhang, S.;Jiang, J. J.;Zhang, Y.;Zhao, L. Y.;Shan, D.;Zhu, W. Z.",2013,Aug,10.1007/s12035-013-8418-6,0,
1264,Multiple diffusion indices reveals white matter degeneration in Alzheimers Disease and mild cognitive impairment: A tract-based spatial statistics study,Alzheimers disease (AD) is a progressive neurodegenerative disease involving the decline of memory and other cognitive functions. Mild cognitive impairment (MCI) represents a transition phase between normal aging and early AD. The degeneration patterns of the white matter across the brain in,,"Shu, N.;Wang, Z.;Qi, Z.;Li, K.;He, Y.",2011,2011,,0,
1265,Disrupted topologic efficiency of white matter structural connectome in individuals with subjective cognitive decline,"Purpose: To determine whether individuals with subjective cognitive decline (SCD), which is defined by memory complaints with normal performance at objective neuropsychologic examinations, exhibit disruptions of white matter (WM) connectivity and topologic alterations of the brain structural connectome. Materials and Methods: Diffusion-tensor magnetic resonance imaging and graph theory approaches were used to investigate the topologic organization of the brain structural connectome in 36 participants with SCD (21 women: mean age, 62.0 years ± 8.6 [standard deviation]; age range, 42-76 years; 15 men: mean age, 65.5 years ± 8.9; age range, 51-80 years) and 51 age-, sex-, and years of education-matched healthy control participants (33 women: mean age, 63.7 years ± 8.8; age range, 46-83 years; 18 men: mean age, 59.4 years ± 9.3; age range, 43-75 years). Individual WM networks were constructed for each participant, and the network properties between two groups were compared with a linear regression model. Results: Graph theory analyses revealed that the participants with SCD had less global efficiency (P = .001) and local efficiency (P = .008) compared with the healthy control participants. Lower regional efficiency was mainly distributed in the bilateral prefrontal regions and left thalamus (P < .05, corrected). Furthermore, a disrupted subnetwork was observed that consisted of widespread anatomic connections (P < .05, corrected), which has the potential to discriminate individuals with SCD from control participants. Moreover, similar hub distributions and less connection strength between the hub regions (P = .023) were found in SCD. Importantly, diminished strength of the rich-club and local connections was correlated with the impaired memory performance in patients with SCD (rich-club connection: r = 0.43, P = .011; local connection: r = 0.36, P = .037). Conclusion: This study demonstrated disrupted topologic efficiency of the brain's structural connectome in participants with SCD and provided potential connectome-based biomarkers for the early detection of cognitive impairment in elderly individuals.",adult;aged;anterior cingulate;area under the curve;article;brain region;caudate nucleus;clinical article;cognitive defect;connectome;controlled study;cuneus;diffusion tensor imaging;female;geriatric patient;human;human tissue;inferior temporal gyrus;lingual gyrus;male;mental deterioration;mental performance;middle frontal gyrus;Mini Mental State Examination;Montreal cognitive assessment;nerve cell network;occipital gyrus;prefrontal cortex;priority journal;prospective study;recall;receiver operating characteristic;Rey auditory verbal learning test;superior frontal gyrus;superior temporal gyrus;thalamus;white matter,"Shu, N.;Wang, X.;Bi, Q.;Zhao, T.;Han, Y.",2018,,10.1148/radiol.2017162696,0,
1266,Disrupted topological organization in white matter structural networks in amnestic mild cognitive impairment: relationship to subtype,"PURPOSE: To investigate the topological alterations of whole-brain white matter structural connectivity in patients with different types of amnestic mild cognitive impairment (aMCI), including single-domain (SD) and multidomain (MD) aMCI, and to explore the relationship of such connectivity with neuropsychologic performance. MATERIALS AND METHODS: This study was approved by the institutional review board of Imaging Center for Brain Research, Beijing Normal University. Written informed consent was obtained from each participant. The present study involved 38 patients with aMCI (SD aMCI, n=18; MD aMCI, n=20) and 36 age- and sex-matched healthy control subjects. White-matter connectional architecture in each participant was depicted with diffusion-weighted MR imaging and represented in terms of a connectivity matrix by using a deterministic tractography method. Graph theory-based analyses were then performed to characterize brain network properties. RESULTS: The global topological organization of white matter networks was significantly disrupted in patients with MD aMCI (P<.01 for all) but not in those with SD aMCI, as compared with control subjects. Connectivity impairment in patients with MD aMCI was found in the temporal, frontal, and parietal cortices (P<.05, corrected). MD aMCI had decreased network efficiency relative to SD aMCI (P=.016), with the most pronounced differences located in the frontal cortex (P<.01 for all). Strong associations between cognitive impairments and disrupted topological features (global, P<.05; regional, P<.002) were identified in patients with aMCI. CONCLUSION: The present study suggests early onset disruption of whole-brain white matter connectivity in patients with aMCI, especially in those with the MD subtype, supporting the view that MD aMCI is a more advanced form of disease than is SD aMCI. Moreover, cognitive correlations with topological network properties suggest their potential use as markers to assess the risk of Alzheimer disease.","Amnesia/ complications/ pathology;Cognition Disorders/ complications/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology;Reproducibility of Results;Sensitivity and Specificity","Shu, N.;Liang, Y.;Li, H.;Zhang, J.;Li, X.;Wang, L.;He, Y.;Wang, Y.;Zhang, Z.",2012,Nov,10.1148/radiol.12112361,0,
1267,Effects of APOE promoter polymorphism on the topological organization of brain structural connectome in nondemented elderly,"The polymorphism of the Apolipoprotein E (APOE) promoter rs405509 can regulate the transcriptional activity of the APOE gene and is related to Alzheimer's disease (AD). However, its effects on cognitive performance and the underlying brain mechanisms remain unknown. Here, we performed a battery of neuropsychological tests in a large sample (837 subjects) of nondemented elderly Chinese people, and explored the related brain mechanisms via the construction of diffusion MRI-based structural connectome and graph analysis from a subset (84 subjects) of the sample. Cognitively, the rs405509 risk allele (TT) carriers showed decreased attention and execution functions compared with noncarriers (GG/GT). Regarding the topological alterations of the brain connectome, the risk allele group exhibited reduced global and local efficiency of white matter structural networks, mainly in the left anterior and posterior cingulate cortices (PCC). Importantly, the efficiency of the left PCC is correlated with the impaired attention function and mediates the impacts of the rs405509 genotype on attention. These results demonstrated that the rs405509 polymorphism affects attention function in nondemented elderly people, possibly by modulating brain structural connectivity of the PCC. This polymorphism may help us to understand the neural mechanisms of cognitive aging and to serve as a potential marker assessing the risk of AD. Hum Brain Mapp 36:4847-4858, 2015. (c) 2015 Wiley Periodicals, Inc.",APOE promoter;brain connectome;cognition;diffusion MRI;graph theory,"Shu, N.;Li, X.;Ma, C.;Zhang, J.;Chen, K.;Liang, Y.;Chen, Y.;Zhang, Z.",2015,Dec,10.1002/hbm.22954,0,
1268,Post-stroke vascular dementia: risk factors and clinical neuro-imaging features,"To analyze the status of risk factors for post-stroke vascular dementia, 128 patients with post-stroke dementia, aged from 50-79 years, have been studied. A control group included 125 patients, aged 50-79 years, with moderate cognitive impairment after stroke. A coronary heart disease was a significant risk factor for the patients aged from 50-59; coronary heart disease, diabetes mellitus, overweight and hyperlipidemia were significant risk factors for the aged 60-69, diabetes mellitus, overweight and hyperlipidemia were significant risk factors for the aged 70-79. The stroke-related factors were cerebral infarction in left hemisphere, frontal and temporo-occipital infarction, thalamic, basal ganglion; cerebral white-matter lesions. The mathematical model of post-stroke dementia prediction was created for patients with post-stroke moderate cognitive impairment.","Aged;Brain/ pathology;Case-Control Studies;Data Interpretation, Statistical;Dementia, Vascular/ etiology/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Neuropsychological Tests;Prognosis;Risk Factors;Severity of Illness Index;Stroke/ complications/ pathology","Shprakh, V. V.;Suvorova, I. A.",2010,,,0,
1269,Magnetic resonance imaging findings in Japanese encephalitis. White matter lesions,"Ten patients with Japanese encephalitis diagnosed by serological criteria underwent magnetic resonance imaging (MRI) in axial and coronal sections. In 6, a second MRI study was done. The MRI findings were compared with the clinical outcome. Four patients died within several months of onset, 2 had sequelae such as hemiparesis and dementia, and the remaining 4 had no sequelae. In 9 of 10 patients, either diffuse or patchy white matter lesions were observed bilaterally, together with abnormalities in areas such as the thalamus, basal ganglia, and brainstem. For 3 patients who died or remained demented, the second MRI revealed extensive, diffuse white matter abnormalities. This study indicates that Japanese encephalitis can produce white matter involvement, although gray matter structures such as the thalamus, basal ganglia, and brainstem are more severely affected. The severity of these MRI lesions correlated with the clinical outcome.","Adolescent;Adult;Aged;Brain/ pathology;Child;Child, Preschool;Encephalitis, Japanese/ diagnosis;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Shoji, H.;Kida, H.;Hino, H.;Matsuura, S.;Kojima, K.;Abe, T.;Utsunomiya, H.;Okada, Y.;Nakamura, Y.;Okudera, T.",1994,Oct,,0,
1270,Brain swelling and loss of gray and white matter differentiation in human postmortem cases by computed tomography,"The purpose of this study was to evaluate the brain by postmortem computed tomography (PMCT) versus antemortem computed tomography (AMCT) using brains from the same patients. We studied 36 nontraumatic subjects who underwent AMCT, PMCT, and pathological autopsy in our hospital between April 2009 and December 2013. PMCT was performed within 20 h after death, followed by pathological autopsy including the brain. Autopsy confirmed the absence of intracranial disorders that might be related to the cause of death or might affect measurements in our study. Width of the third ventricle, width of the central sulcus, and attenuation in gray matter (GM) and white matter (WM) from the same area of the basal ganglia, centrum semiovale, and high convexity were statistically compared between AMCT and PMCT. Both the width of the third ventricle and the central sulcus were significantly shorter in PMCT than in AMCT (P < 0.0001). GM attenuation increased after death at the level of the centrum semiovale and high convexity, but the differences were not statistically significant considering the differences in attenuation among the different computed tomography scanners. WM attenuation significantly increased after death at all levels (P<0.0001). The differences were larger than the differences in scanners. GM/WM ratio of attenuation was significantly lower by PMCT than by AMCT at all levels (P<0.0001). PMCT showed an increase in WM attenuation, loss of GM-WM differentiation, and brain swelling, evidenced by a decrease in the size of ventricles and sulci.",adult;aged;antemortem computed tomography;article;autopsy;basal ganglion;brain cortex;brain disease;brain infarction;brain slice;brain swelling;brain third ventricle;brain third ventricle width;cancer infiltration;cause of death;central pontine myelinolysis;central sulcus;central sulcus width;centrum semiovale;clinical evaluation;clinical feature;computed tomography scanner;controlled study;diffuse Lewy body disease;female;gray matter;human;imaging phantom;intermethod comparison;male;meningioma;multidetector computed tomography;nerve cell differentiation;nervous system parameters;neuropathology;posthumous care;postmortem computed tomography;subdural hematoma;swelling;white matter;Aquilion 64;Aquilion ONE,"Shirota, G.;Gonoi, W.;Ishida, M.;Okuma, H.;Shintani, Y.;Abe, H.;Takazawa, Y.;Ikemura, M.;Fukayama, M.;Ohtomo, K.",2015,,,0,
1271,A case of carbon monoxide intoxication presenting subacute dementia as the initial symptom,"We reported a 67-year-old woman who had developed abnormal behavior and dementia from January 21, 2001 and deteriorated to akinetic mutism on February 15. T2-weighted magnetic resonance imaging showed high intensity in bilateral globus pallidus and a rapid spreading of diffuse high intensity in bilateral deep white matter. Later on, we got an important information that she had used a little coal stove three times about three weeks before presenting the initial symptom. She was diagnosed as carbon monoxide intoxication and treated with hyperbaric oxygen from March 1. A remarkable improvement on dementia and motor disability was observed. We conclude that this case is the first reported example of a case of intermittent carbon monoxide intoxication presenting subacute dementia as an initial symptom.",,"Shiote, M.;Kido, Y.;Hayashi, T.;Matubara, E.;Manabe, Y.;Shoji, M.;Abe, K.",2002,1,,0,
1272,Long-term effect of low-frequency repetitive transcranial magnetic stimulation over the unaffected posterior parietal cortex in patients with unilateral spatial neglect,"Objective: To explore long-term effects on unilateral spatial neglect of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected posterior parietal cortex. Design: Uncontrolled pilot study. Subjects: Two chronic-phase patients with left-sided unilateral spatial neglect from cerebral infarction. Methods: Six rTMS sessions were under taken for 2 weeks. Each session included 900 stimuli applied over P5 at an intensity of 95% motor thresholds and a frequency of 0.9 Hz. The Behavioural Inattention Test, either the Mini-Mental State Examination or the Revised Hasegawa Dementia Scale, Brunnstrom Recovery Stage, and Barthel Index were evaluated at 2-week intervals until 6 weeks after rTMS sessions. Single-photon emission computed tomography was performed 2 weeks before and after rTMS. Results: Behavioural Inattention Test scores improved remarkably, especially from 2 to 4 weeks after rTMS sessions. At 6 weeks, Behavioural Inattention Test scores still remained above pre-rTMS levels. Other clinical evaluations as well as single-photon emission computed tomography showed no significant change during the study. Conclusion: In this small pilot study, low-frequency rTMS over the unaffected posterior parietal cortex decreased unilateral spatial neglect for at least 6 weeks. © 2006 Taylor & Francis.",adult;article;attention disturbance;Barthel index;behavior;brain infarction;case report;decompression surgery;dementia;female;human;male;Mini Mental State Examination;motor performance;parietal lobe;perceptive threshold;performance;pilot study;rating scale;single photon emission computer tomography;therapy effect;transcranial magnetic stimulation;treatment duration;unilateral spatial neglect,"Shindo, K.;Sugiyama, K.;Huabao, L.;Nishijima, K.;Kondo, T.;Izumi, S. I.",2006,,,0,
1273,Blood-brain barrier dysfunction in white matter lesions of elderly patients with dementia,"We investigated blood-brain barrier (BBB) permeability in white matter lesions of Binswanger's and Alzheimer's disease with contrast-enhanced MRI. BBB permeability was quantified by calculation of T1 change defined as [(T1post-T1pre)/T1pre], where T1pre and T1post represent the T1 relaxation times before and after Gd-DTPA administration. T1 changes in periventricular hyperintensity (PVH) of BD and AD patients significantly decreased in comparison with that in normal white matter of the control subjects, and PVH of BD patients showed significantly decreased T1 change compared to PVH of AD. The magnetization transfer ratio (MTR), reflecting the severity of tissue damage in the white matter, significantly decreased in PVH of BD and AD patients comfarmd with normal white matter of the controls, with a significant decrease in PVH of BD patients compared to PVH of AD patients. T1 change and MTR for area of PVH significantly correlated with the MMSE score in BD, but not in AD. These results suggest that BBB permeability increases in areas of PVH in BD and AD. Moreover, increased BBB permeability may be related to a decline in cognitive impairment in patients with BD. BBB dysfunction and tissue damage may be more severe in areas of PVH in BD patients than that in AD patients.",gadolinium pentetate;aged;article;Binswanger encephalopathy;blood brain barrier;brain injury;clinical article;cognitive defect;contrast enhancement;controlled study;dementia;female;human;male;nuclear magnetic resonance imaging;tissue injury;white matter,"Shindo, H.;Hanyu, H.;Shimizu, S.;Iwamoto, T.",2005,,,0,
1274,Subcortical white matter hyperintensities within the cholinergic pathways of Parkinson's disease patients according to cognitive status,"Background: White matter hyperintensities (WMH) in the cholinergic pathways show a stronger correlation with cognitive performance than general WMH in Alzheimer's disease. However, the role of WMH within the cholinergic pathways in cognitive dysfunction has not been investigated in Parkinson's disease (PD). Method: The severity of WMH within the cholinergic pathways of PD subgroups with intact cognition (PD-IC, n=44), mild cognitive impairment (PD-MCI, n=87) and dementia (PDD, n=40) were compared using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and the correlation between the CHIPS score and performance on individual tests of cognitive subdomains were analysed. Results The mean CHIPS score was significantly higher in patients with PDD compared with those with PD-IC (p=0.03) or PD-MCI (p=0.015). The CHIPS score in patients with PD was negatively correlated with general cognition assessed using the Mini-Mental State Examination (r=-0.28, p<0.001) and positively with the Unified Parkinson's Disease Rating Scale motor score (r=0.24, p=0.002). The CHIPS score showed a significant correlation with cognitive performance on individual cognitive subdomains and had the highest independent correlations with contrasting programme (β=-0.33, p<0.001) and forward digit span (β=-0.17, p=0.04). Conclusions: This study demonstrated that the burden of WMH within cholinergic pathways was significantly higher in patients with PDD relative to other groups, and that cholinergic WMH was significantly correlated with a decline in frontal executive function and attention.",aged;article;Cholinergic Pathways Hyperintensities Scale;cholinergic system;cognition;controlled study;dementia;female;human;image analysis;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;Parkinson disease;priority journal;radiological parameters;rating scale;scoring system;Unified Parkinson Disease Rating Scale;white matter hyperintensity,"Shin, J.;Choi, S.;Lee, J. E.;Lee, H. S.;Sohn, Y. H.;Lee, P. H.",2012,,,0,
1275,"Elevated glucose level adversely affects infarct volume growth and neurological deterioration in non-diabetic stroke patients, but not diabetic stroke patients","Background and purpose: Hyperglycemia is recognized as a common occurrence associated with a high risk of poor outcome in ischaemic stroke patients. However, little is known about the association between elevated glucose level, growth of infarct volume and neurological deterioration in ischaemic stroke patients without diabetes. The present study aimed to clarify this issue in acute ischaemic stroke patients with arterial occlusion. Methods: We studied 375 acute ischaemic stroke patients with arterial occlusion within 24h of onset. Diabetes was diagnosed in patients with a known history of diabetes or HbA1c value ≥6.5%. Infarct volume was measured on admission and at follow-up within 48h using diffusion-weighted imaging. Neurological deterioration was defined as an increase of ≥4points in National Institutes of Health Stroke Scale score within 7days of stroke onset. We examined the relationship between glucose level on admission, infarct volume growth and neurological deterioration in three categories (all patients, non-diabetes and diabetes) using multivariate modeling. Results: Diabetes was present in 104 patients (27.7%). Multivariate regression analysis showed that elevated glucose level was independently associated with infarct volume growth in all patients (P=0.034) and non-diabetes (P=0.002), but not in diabetes (P=0.871). Moreover, elevated glucose level was independently associated with neurological deterioration in all patients [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.004-1.017; P=0.002] and non-diabetes (OR, 1.014; 95% CI, 1.002-1.026; P=0.022), but not diabetes (OR, 1.006; 95% CI, 0.998-1.014; P=0.151). Conclusions: Glucose level appears to influence infarct volume growth and neurological deterioration, particularly in non-diabetic patients with ischaemic stroke. © 2013 The Author(s). European Journal of Neurology © 2013 EFNS.",,"Shimoyama, T.;Kimura, K.;Uemura, J.;Saji, N.;Shibazaki, K.",2014,March,,0,
1276,Diffusional kurtosis imaging analysis in patients with hypertension,"Purpose: Hypertension is associated with substantial morbidity in Japan. The aim of this work was to evaluate whether hypertension is associated with white matter microstructural changes by using diffusional kurtosis imaging (DKI). Methods: We explored the regional patterns of white matter alteration in 15 hypertensive middle-aged male participants and 11 normotensive controls by using DKI-based whole-brain analysis. In addition, we investigated whether the observed white matter microstructural changes were related to systolic or diastolic blood pressure by using Pearson's correlation coefficient analysis. Results: Mean diffusional kurtosis (MDK) values were significantly higher in hypertensive participants than in normotensive participants (P < 0.05; family-wise error correction for multiple comparisons), indicating widespread microstructural changes in white matter. Moreover, we noted a statistically significant positive correlation between systolic and diastolic blood pressure and MDK values of the whole brain. Conclusion: Our study suggests that microstructural white matter changes occur in middle-aged men with hypertension, even before the onset of cerebrovascular disease. Thus, DKI might be used as a screening tool for risk of cerebrovascular disease. This highlights the need to further elucidate the relationship between hypertension and DKI of the brain. © 2014 Japan Radiological Society.",,"Shimoji, K.;Uka, T.;Tamura, Y.;Yoshida, M.;Kamagata, K.;Hori, M.;Motoi, Y.;Watada, H.;Kawamori, R.;Aoki, S.",2014,February,,0,
1277,A patient with HIV encephalopathy presenting with parkinsonism during HAART therapy,"We report the case of a 32-year-old man presenting symptoms of parkinsonism. Neurological examination revealed parkinsonism symptoms such as akinesia and postural instability, dementia and frontal lobe signs. He was diagnosed as having human immunodeficiency virus (HIV) encephalopathy. Brain MRI, 99mTc ECD-SPECT and 1H-MR spectroscopy demonstrated symmetrical cerebral white matter lesions, predominantly in the bilateral frontal lobes. Frontal lobe dysfunction could be responsible for his parkinsonism associated with HIV encephalopathy. His neurological symptoms improved transiently after the initiation of HAART but fluctuated when antiretroviral drugs were changed because of their side effects. Although HAART effectively decreased plasma HIV-RNA load and increased peripheral blood CD4 cell count, his parkinsonism and dementia eventually exacerbated. Our results suggest that a combination of antiretroviral drugs affects the therapeutic efficacy against HIV encephalopathy, and that CNS symptoms could be aggravated during HAART, even when plasma HIV-RNA load and CD4 cell count are maintained under favorable conditions.",antiretrovirus agent;cysteine ethyl ester tc 99m;virus RNA;adult;article;case report;CD4 lymphocyte count;clinical feature;disease association;highly active antiretroviral therapy;human;Human immunodeficiency virus;Human immunodeficiency virus infection;male;neurologic examination;nuclear magnetic resonance imaging;nuclear magnetic resonance spectroscopy;parkinsonism;single photon emission computer tomography;unspecified side effect,"Shimohata, T.;Takadou, Y.;Terajima, K.;Tsukada, H.;Gejo, F.;Tanaka, K.;Nishizawa, M.",2006,,,0,
1278,Leukoencephalopathy-related cerebral amyloid angiopathy with cystatin C deposition,"Background: We have described sporadic cases of cerebral amyloid angiopathy with cerebral hemorrhage showing a low cystatin C level in the cerebrospinal fluid detected by enzyme-linked immunosorbent assay. Recently, several cases of leukoencephalopathy in patients with cerebral amyloid angiopathy have been reported. We describe a sporadic case of leukoencephalopathy with cystatin C-type cerebral amyloid angiopathy diagnosed during life by enzyme-linked immunosorbent assay. Case Description: A 74-year-old man who had suffered from progressive dementia for 3 years was admitted with right hemiparesis, dysarthria, and ataxia. MRI revealed pontine infarction and multiple lacunar state with leukoaraiosis. We suspected cystatin C-type cerebral amyloid angiopathy because of the low level of cystatin C in the cerebrospinal fluid. The patient died of sepsis 3 months later, and the presence of leukoencephalopathy with cerebral amyloid angiopathy was confirmed by autopsy. Immunohistological examination disclosed cystatin C and β-protein deposition in amyloid structures of the cortical cerebral arteries. Conclusions: Measurement of cystatin C in the cerebrospinal fluid by enzyme-linked immunosorbent assay is a useful method of diagnosing leukoencephalopathy related to sporadic cystatin C-type cerebral amyloid angiopathy.",cystatin C;aged;article;brain biopsy;brain hemorrhage;case report;clinical feature;enzyme linked immunosorbent assay;histopathology;human;immunohistochemistry;leukoencephalopathy;male;priority journal;protein determination,"Shimode, K.;Kobayashi, S.;Imaoka, K.;Umegae, N.;Nagai, A.",1996,,,0,
1279,A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in which lomerizine hydrochloride was suggested to prevent recurrent stroke,"A 60-year-old man visited our hospital because of left hemiparesis in September 2006. Magnetic resonance imaging (MRI) revealed a high-intensity lesions in the right corona radiata on diffusion-weighted images and a high-intensity lesions in the basal ganglia and deep white matter on T(2)-weighted images. He recovered with no sequelae. Antithrombotic agents such as aspirin were given to prevent stroke, but stroke recurred three times over the course of 3 years. In February 2009, neurological examination revealed right hemiparalysis and dysarthria. Dysphagia and cognitive decline had been progressing gradually. We suspected cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) on the basis of the clinical and family history. An Arg75Pro mutation in the Notch3 gene was found, but did not involve a cysteine residue. Antithrombotic agents were ineffective. We tried lomerizine hydrochloride, which was reported to prevent stroke in a patient with CADASIL. In Japan, lomerizine hydrochloride is used to prevent migraine and to selectively inhibit cerebral artery contraction. During treatment with lomerizine hydrochloride (5 mg/day) for more than 3 years, there was no recurrence of cerebral infarction and no further deterioration of cognitive function or MRI findings. There is no evidence supporting the efficacy of antithrombotic agents in CADASIL patients. Moreover, antithrombotic agents have been reported to increase the frequency of clinically silent microbleeds on MRI in CADASIL. Lomerizine hydrochloride might therefore be one option for the treatment of CADASIL.",,"Shimizu, H.;Nagami, S.;Takahashi, N.",2014,2014,,0,
1280,Effects of medial temporal atrophy and white matter hyperintensities on the cognitive functions in patients with Alzheimer's disease,"AIMS: We conducted this study to investigate the independent association of medial temporal atrophy (MTA) and white matter hyperintensities (WMH) with cognitive impairments of Alzheimer's disease (AD) patients and the interaction between MTA and WMH. METHODS: From 13 centers, a total of 216 AD patients were consecutively recruited and their MTA and WMH were visually rated. We evaluated the association of MTA and WMH with the various cognitive domains, and the interaction between MTA and WMH. RESULTS: MTA independently correlated with scores of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), delayed recalls of the Seoul Verbal Learning Test (SVLT), the Boston Naming Test (BNT), and Word Fluency. WMH independently correlated with MMSE, CDR, Digit Span, and Stroop word reading, but not with delayed recall. There were interactions of WMH and MTA on CDR (p = 0.004), SVLT (p = 0.023), BNT (p = 0.002) and the semantic Word Fluency (p = 0.007). CONCLUSION: MTA and WMH independently affected cognitive deficits in AD patients, with somewhat different patterns where MTA was associated mostly with memory and language, while WMH were associated with attention and frontal executive functions. This study also showed interactions between MTA and WMH on some cognitive deficits and dementia severity, suggesting that they synergistically contribute to cognitive impairment in AD.","Aged;Aged, 80 and over;Alzheimer Disease/*complications;Atrophy/pathology;Cognition Disorders/*etiology/*pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mental Recall/physiology;Mental Status Schedule;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Temporal Lobe/*pathology;Verbal Learning","Shim, Y. S.;Youn, Y. C.;Na, D. L.;Kim, S. Y.;Cheong, H. K.;Moon, S. Y.;Park, K. W.;Ku, B. D.;Lee, J. Y.;Jeong, J. H.;Kang, H.;Kim, E. J.;Lee, J. S.;Go, S. M.;Kim, S. H.;Cha, K. R.;Seo, S. W.",2011,,10.1159/000329277,0,
1281,Pathological correlates of white matter hyperintensities on magnetic resonance imaging,"Background/Aims: We investigated the histopathological correlates of white matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD) or cerebrovascular disease, and in aged controls. Methods: We reviewed 57 participants who had neuropathology and in whom neuroimaging was done. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small-vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs was investigated in 14 participants. The variables included: demyelination of the deep and periventricular white matter (WM), atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman's rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. Results: The severity of arteriosclerosis was correlated with the volume of periventricular hyperintensity (PVH) estimated by magnetic resonance imaging. Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs, and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. Conclusion: WMHs are consistent with small-vessel disease and increase the tissue water content. We found no association between WMHs and the thickness of small blood vessels.",,"Shim, Y. S.;Yang, D. W.;Roe, C. M.;Coats, M. A.;Benzinger, T. L.;Xiong, C.;Galvin, J. E.;Cairns, N. J.;Morris, J. C.",2014,4,,0,
1282,Comparison of regional cerebral blood flow in two subsets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT,"BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Erkinjuntti, incorporated two clinical entities, the lacunar state and Binswanger's disease. However it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of regional cerebral blood flow (CBF) in the two subsets of SIVD to establish whether these two subtypes could be incorporated into the same group for the purpose of conducting clinical trials. METHODS: Twelve SIVD patients with predominant white matter lesions, 13 patients with predominant lacunar infarctions and 17 controls were evaluated. Single photon emission computed tomography (SPECT) was performed to measure the regional CBF, and statistical parametric mapping (SPM) was applied to the analysis of the SPECT data. RESULTS: The normalized CBF (nCBF) in the bilateral thalami, the anterior cingulate gyri, the superior temporal gyri, the caudate heads and the left parahippocampal gyrus was significantly decreased in the SIVD patients compared to the controls. This pattern of nCBF reduction was same in both the two subtypes of SIVD patients. CONCLUSION: Our study suggests that the two subsets of SIVD may have a common nCBF abnormality, and Erkinjuntti's criteria offer a solution for researchers to identify the more homogeneous group of vascular dementia patients.","Aged;Brain Infarction/physiopathology/radionuclide imaging;Brain Ischemia/physiopathology/ radionuclide imaging;Brain Mapping/methods;Cerebral Arteries/physiopathology/ radionuclide imaging;Cerebrovascular Circulation/ physiology;Data Interpretation, Statistical;Dementia, Vascular/physiopathology/ radionuclide imaging;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests;Telencephalon/blood supply/physiopathology/ radionuclide imaging;Tomography, Emission-Computed, Single-Photon/ methods","Shim, Y. S.;Yang, D. W.;Kim, B. S.;Shon, Y. M.;Chung, Y. A.",2006,Dec 1,10.1016/j.jns.2006.07.008,0,
1283,A serial study of regional cerebral blood flow deficits in patients with left anterior thalamic infarction: anatomical and neuropsychological correlates,"Thalamic damage is associated with a variety of neuropsychological dysfunctions, as well as strategic infarct dementia. However, only a limited number of reports in the medical literature have discussed the correlation between the clinical findings and the specific functional changes observed on images. We investigated the neuropsychological correlation of the regional cerebral blood flow (rCBF) deficits in four patients with left anterior thalamic infarction within two days after their stroke. All of the patients showed anterograde amnesia on the verbal memory test. Some dysexecutive features were present such as decreased word fluency and an impaired performance on the Stroop test. A decreased rCBF was observed in the left supramarginal gyrus, the superior temporal gyrus, the middle and inferior frontal gyri, and the medial dorsal and anterior nuclei of the left thalamus. The changes of rCBF may have been due to remote suppression by the interruption of the thalamo-cortical circuit that connects the anterior thalamic nucleus and various cortical areas. These initial findings remained unchanged even on the follow-up studies.","Aged;Attention/physiology;Brain Mapping;Cerebral Infarction/ pathology/physiopathology/psychology;Cerebrovascular Disorders/ pathology/physiopathology/psychology;Diffusion Magnetic Resonance Imaging;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests;Stroke/ pathology/physiopathology/psychology;Thalamus/blood supply/ pathology;Tomography, Emission-Computed, Single-Photon","Shim, Y. S.;Kim, J. S.;Shon, Y. M.;Chung, Y. A.;Ahn, K. J.;Yang, D. W.",2008,Mar 15,10.1016/j.jns.2007.09.016,0,
1284,Cognitive correlates of cerebral vasoreactivity on transcranial doppler in older adults,"Background This study was performed to explore the possible contributions of cerebral hemodynamic changes to the cognitive impairment in patients with Alzheimer's disease (AD). Methods A total of 194 participants were included: 52 controls, 75 patients with mild cognitive impairment (MCI), and 67 patients with AD. Demographic characteristics, vascular risks, mini-mental state examination (MMSE), and clinical dementia rating (CDR) were assessed, and magnetic resonance imaging of the brain was performed to evaluate white matter hyperintensities (WMHs). Using transcranial Doppler (TCD) ultrasonography, cerebrovascular reactivity (CVR) was evaluated with a breath-holding test, in addition to the mean blood flow velocity (MFV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery. Results After adjusting for covariates such as age, education, WMH severity, and vascular risks, TCD parameters such as MFV, PI, and RI did not differ between the 3 groups. However, CVR was significantly reduced in the",,"Shim, Y.;Yoon, B.;Shim, D. S.;Kim, W.;An, J. Y.;Yang, D. W.",2015,1,,0,
1285,Predicting neurocognitive function with hippocampal volumes and DTI metrics in patients with Alzheimer's dementia and mild cognitive impairment,"INTRODUCTION: Cognitive performance in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM). We aimed to predict the neurocognitive functions of patients with MCI or AD using hippocampal volumes and diffusion tensor imaging (DTI) metrics via partial least squares regression (PLSR). METHODS: A total of 148 elderly female subjects were included: AD (n = 49), MCI (n = 66), and healthy controls (n = 33). Twenty-four hippocampal subfield volumes and the average values for fractional anisotropy (FA) and mean diffusivity (MD) of 48 WM tracts were used as predictors, CERAD-K total scores, scores of CERAD-K 7 cognitive subdomains and K-GDS were used as dependent variables in PLSR. RESULTS: Regarding MCI patients, DTI metrics such as the MD values of the left retrolenticular part of the internal capsule and left fornix (cres)/stria terminalis were significant predictors, while hippocampal subfield volumes, like the left CA1 and hippocampal tail, were main contributors to cognitive function in AD patients, although global FA/MD values were also strong predictors. The 10-fold cross-validation and stricter 300-iteration tests proved that global cognition measured by the CERAD-K total scores and the scores of several CERAD-K subdomains can be reliably predicted using the PLSR models. CONCLUSIONS: Our findings indicate different structural contributions to cognitive function in MCI and AD patients, implying that diffuse WM microstructural changes may precede hippocampal atrophy during the AD neurodegenerative process.",Alzheimer's dementia;diffusion tensor imaging;hippocampal volume;mild cognitive impairment;partial least squares regression,"Shim, G.;Choi, K. Y.;Kim, D.;Suh, S. I.;Lee, S.;Jeong, H. G.;Jeong, B.",2017,Sep,,0,
1286,Morphometric characterization of Binswanger's disease: comparison with Alzheimer's disease,"BACKGROUND AND PURPOSE: Dementia due to hypertensive vascular disease is a potential target to treat prophylactively before it progresses insidiously. Binswanger's disease (BD) is a type of subcortical vascular dementia, but its clinical features and pathophysiology are still obscure. We therefore tried to find a topographic distribution of brain atrophy in BD by morphometric analysis. METHODS: Twenty patients with BD, 50 patients with AD, and 80 elderly controls were recruited. We contrasted the gray matter atrophy of BD to that of AD to identify a pathognomic pattern using magnetic resonance imaging. We used DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) for voxel-based morphometry, expecting that its sophisticated algorithm would work well to deal with the subjects with brain atrophy. RESULTS: Atrophy of cortices was predominant in the posterior cortices in AD but was in the anterior cortices in BD. Atrophy of amygdala and hippocampus was similar in each disease. In contrast, thalamus, caudate nucleus, insula, anterior cingulate cortex, and frontal cortices were significantly more atrophied in BD than in AD (z-score >3). CONCLUSIONS: We demonstrated topographic patterns of brain atrophy in BD. Since affected regions of BD match with the anatomical connections of frontal-subcortical circuits, it seems reasonable to suppose that BD pathology is the result of hypertensive vascular disease and subsequent regression from the white matter injuries.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Dementia, Vascular/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Shiino, A.;Akiguchi, I.;Watanabe, T.;Shirakashi, Y.;Nozaki, K.;Tooyama, I.;Inubushi, T.",2012,Sep,10.1016/j.ejrad.2011.05.031,0,
1287,I-123 hydroxyiodobenzyl propanediamine (HIPDM) cerebral blood flow imaging demonstrating transtentorial diaschisis,"To assess the clinical significance of transtentorial diaschisis (TTD) as demonstrated by I-123 HIPDM brain imaging, SPECT and/or planar images of 35 patients with stroke, 26 patients with Alzheimer's disease (AD), 2 patients with Creutzfeldt-Jakob disease (CJD), and 1 patient with a schizoaffective disorder were analyzed. TTD was observed in 21 of the 35 patients with strokes. In 13 stroke patients, TTD was associated with large infarcts in the middle cerebral artery (MCA) territory; in the remaining 8 stroke patients, TTD was associated with internal capsule and/or basal ganglia infarcts. TTD was not associated with small occipital or parietal infarcts. Despite cortical perfusion decrements, TTD was not seen in the AD patients, the CJD patients, or the patient with schizoaffective disorder. It is concluded that 1) TTD frequently occurs following cerebral infarct of the MCA territory (60% of the patients in this sample); 2) absence of TTD in the presence of a large cerebral perfusion abnormality may represent neuronal dysfunction of the cerebral cortex; and 3) the presence of TTD without a significant cortical perfusion abnormality may indicate basal ganglia and/or internal capsule infarct.","Alzheimer Disease/ radionuclide imaging;Brain/ radionuclide imaging;Cerebral Infarction/radionuclide imaging;Cerebrovascular Circulation/physiology;Cerebrovascular Disorders/ radionuclide imaging;Humans;Iodine Radioisotopes;Iodobenzenes;Tomography, Emission-Computed, Single-Photon","Shih, W. J.;Dekosky, S. T.;Coupal, J. J.;Simmons, G.;Pulmano, C.;Kung, H. F.;Ryo, U. Y.;Clark, D. B.",1990,Sep,,0,
1288,Reconstruction of the human cerebral cortex robust to white matter lesions: Method and validation,"Cortical atrophy has been reported in a number of diseases, such as multiple sclerosis and Alzheimer's disease, that are also associated with white matter (WM) lesions. However, most cortical reconstruction techniques do not account for these pathologies, thereby requiring additional processing to correct for the effect of WM lesions. In this work, we introduce CRUISE(+), an automated process for cortical reconstruction from magnetic resonance brain images with WM lesions. The process extends previously well validated methods to allow for multichannel input images and to accommodate for the presence of WM lesions. We provide new validation data and tools for measuring the accuracy of cortical reconstruction methods on healthy brains as well as brains with multiple sclerosis lesions. Using this data, we validate the accuracy of CRUISE(+) and compare it to another state-of-the-art cortical reconstruction tool. Our results demonstrate that CRUISE(+) has superior performance in the cortical regions near WM lesions, and similar performance in other regions. Hum Brain Mapp 35:3385-3401, 2014. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.",,"Shiee, N.;Bazin, P. L.;Cuzzocreo, J. L.;Ye, C.;Kishore, B.;Carass, A.;Calabresi, P. A.;Reich, D. S.;Prince, J. L.;Pham, D. L.",2014,July,,0,
1289,Neuroimaging in cerebral small vessel disease: Update and new concepts,"In recent years, small vessel disease (SVD) has been recognized for its major impact on cognitive impairment in elderly people, where it is often difficult to separate its effects from those of neurodegenerative diseases individually. SVD is a systemic disease, probably related to diffuse endothelial dysfunction, which affects the perforating arterioles, capillaries and venules in the brain. Although often asymptomatic, it is responsible for almost half of all dementia cases and a significant proportion of stroke cases. Imaging features found on magnetic resonance include recent small subcortical infarctions, lacunes of presumed vascular origin, white matter hyperintensity of presumed vascular origin, prominent perivascular spaces and cerebral microbleeds. The recognition of these imaging findings as a spectrum of the same disease caused by endothelial dysfunction of small cerebral vessels can allow an overall analysis of the disease and thus the development of more effective preventive and therapeutic strategies.",magnetic resonance;neuroimaging;small vessel disease,"Shibuya, M.;Leite, C. D. C.;Lucato, L. T.",2017,Oct-Dec,,0,
1290,Diffusion tensor imaging assessment of white matter microstructure and medial temporal lobe atrophy in patients with mild Alzheimer disease,"Objective: To evaluate white matter integrity and medial temporal atrophy (MTA) in patients with mild Alzheimer disease (AD) by using DTI and MTA visual scale, and to investigate their relationship with cognitive function. Methods: Forty-four subjects, including 23 mild probable AD (AD group) and 21 normal elders (NC group) were examined using DTI technology and ROI method. Mean diffusivity (MD) and partial FA value were measured. Medial temporal lobe atrophy was assessed with MTA. Independent sample t-test and canonical correlation analysis were used. Results: Compared to NC group, FA value in bilateral parahippocampal, posterior cingulate, inferior longitudinal fasciculus, inferior fronto-occipital fascicles decreased significantly, while MD value of bilateral parahippocampal, posterior cingulate, inferior fronto-occipital fascicles, and left inferior longitudinal fasciculus, left uncinate fasciculus increased significantly in",,"Shi, S.;Yuan, H. S.;Liao, J.;Wang, H. L.;Yu, X.",2012,November,,0,
1291,"Relationship between serum Helicobacter pylori-IgG, homocysteic acid with elderly vascular dementia and cerebral infarction",,homocysteic acid;immunoglobulin G;adult;aged;article;brain infarction;clinical article;computer assisted tomography;disease association;elderly care;enzyme linked immunosorbent assay;female;Helicobacter infection;Helicobacter pylori;human;immunoglobulin blood level;male;multiinfarct dementia;nuclear magnetic resonance imaging;protein blood level,"Shi, Q. Y.;Zhang, R. B.;Zhang, Q. Z.",2008,,,0,
1292,Abnormal organization of white matter network in patients with no dementia after ischemic stroke,"Structural changes after ischemic stroke could affect information communication extensively in the brain network. It is likely that the defects in the white matter (WM) network play a key role in information interchange. In this study, we used graph theoretical analysis to examine potential organization alteration in the WM network architecture derived from diffusion tensor images from subjects with no dementia and experienced stroke in the past 5.4-14.8 months (N = 47, Mini-Mental Screening Examination, MMSE range 18-30), compared with a normal control group with 44 age and gender-matched healthy volunteers (MMSE range 26-30). Region-wise connectivity was derived from fiber connection density of 90 different cortical and subcortical parcellations across the whole brain. Both normal controls and patients with chronic stroke exhibited efficient small-world properties in their WM structural networks. Compared with normal controls, topological efficiency was basically unaltered in the patients with chronic stroke, as reflected by unchanged local and global clustering coefficient, characteristic path length, and regional efficiency. No significant difference in hub distribution was found between normal control and patient groups. Patients with chronic stroke, however, were found to have reduced betweenness centrality and predominantly located in the orbitofrontal cortex, whereas increased betweenness centrality and vulnerability were observed in parietal-occipital cortex. The National Institutes of Health Stroke Scale (NIHSS) score of patient is correlated with the betweenness centrality of right pallidum and local clustering coefficient of left superior occipital gyrus. Our findings suggest that patients with chronic stroke still exhibit efficient small-world organization and unaltered topological efficiency, with altered topology at orbitofrontal cortex and parietal-occipital cortex in the overall structural network. Findings from this study could help in understanding the mechanism of cognitive impairment and functional compensation occurred in patients with chronic stroke.","Aged;Dementia/ pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology/physiology;Stroke/ pathology/physiopathology","Shi, L.;Wang, D.;Chu, W. C.;Liu, S.;Xiong, Y.;Wang, Y.;Wong, L. K.;Mok, V. C.",2013,,10.1371/journal.pone.0081388,0,
1293,Clinical characteristics and treatment delay of cerebral infarction in tuberculous meningitis,"BACKGROUND: Cerebral infarction (CI) complicating tuberculous meningitis (TBM) is a major risk factor of permanent disability. The prevention of this complication is an important issue in the quality care of TBM patients. AIM: Our aim was to evaluate the clinical characteristics of TBM patients with CI. METHODS: Ninety-one adult patients with TBM were studied between 1999 and 2007. Clinical, neuroradiological and cerebrospinal fluid data of patients with CI were compared with those without CI. RESULTS: Thirty of the 91 patients had CI, including symptomatic CI occurring before admission in 10 patients, symptomatic CI occurring during hospitalisation in four and silent CI in 16 patients. When compared with non-CI patients, patients with CI were younger and associated with focal weakness on presentation, and had basal meningeal enhancement and hydrocephalus on brain images. Prolonged doctor delays of antituberculosis and steroid therapies, neurosurgical intervention, focal weakness and dementia as sequelae, and poor outcomes were associated with patients with CI than non-CI patients. CONCLUSION: Contrast-enhanced brain imaging is helpful to explore the basal meningeal enhancement in CI patients, and contributes to early diagnosis and treatment of TBM. Early antituberculosis and steroid therapies may help prevent CI in TBM patients.","Adrenal Cortex Hormones/therapeutic use;Adult;Antitubercular Agents/therapeutic use;Brain Damage, Chronic/etiology/prevention & control;Cerebral Infarction/drug therapy/epidemiology/ etiology/surgery;Contrast Media;Delayed Diagnosis;Female;Humans;Inpatients;Magnetic Resonance Imaging;Male;Neuroimaging;Retrospective Studies;Taiwan/epidemiology;Time Factors;Tomography, X-Ray Computed;Treatment Outcome;Tuberculosis, Meningeal/ complications/drug therapy","Sheu, J. J.;Hsu, C. Y.;Yuan, R. Y.;Yang, C. C.",2012,Mar,10.1111/j.1445-5994.2010.02256.x,0,
1294,EEG in silent small vessel disease: sLORETA mapping reveals cortical sources of vascular cognitive impairment no dementia in the default mode network,"INTRODUCTION: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presof the small vessel subcortical subtype may be insidious and difficult to diagnose in the initial stage. We investigated electroencephalographic sources of subcortical vCIND in comparison to amnesic multidomain mild cognitive impairment (amdMCI) to determine the additional diagnostic value of quantitative electroencephalograhy (EEG) in this setting. METHODS: Fifty-seven community residing patients with an uneventful central neurological history and first presentation of cognitive decline without dementia were included, 35 patients were diagnosed with vCIND and 22 with amdMCI. A cognitive control group, deliberately recruited from a cerebrovascular impaired cohort, consisted of cognitively healthy participants who experienced a fully recovered first ever transient ischemic attack (TIA) without clinical or magnetic resonance imaging evidence of stroke. From standard EEGs, the differences in standardized low-resolution brain electromagnetic tomography (sLORETA) sources were determined for the discrete frequency ranges 1-4 (delta), 4-8 (theta), 8-10.5 (alpha1), 10.5-13 (alpha2), 13-22 (beta1), and 22-30 (beta2) Hz. RESULTS: In vCIND, a statistically significant decrease in parietooccipital alpha1 relative power current density compared with TIA and mild cognitive impairment patients was found. There was a significant decrease in frontal and parietooccipital beta1 relative power current density in vCIND compared with TIA patients. A significant increase in (pre) frontal delta relative power current density in vCIND compared with amdMCI was found as well. In amdMCI, delta relative power current density was significantly increased in the core limbic system. DISCUSSION: Cortical sources of abnormal EEG activity in regions implicated in the default mode network are revealed by sLORETA at an early stage in vascular cognitive impairment. Mapping of parietooccipital alpha1, frontoparietooccipital beta1 and (pre) frontal delta loci in vCIND may reflect early executive and visuospatial dysfunction in this cohort. Standard EEG with sLORETA mapping might be an additional, noninvasive, and cost-effective tool in the diagnostic workup of patients presenting with a cognitive decline.","Aged;Brain/pathology/ physiopathology;Brain Mapping;Cerebrovascular Disorders/pathology/ physiopathology;Cognition Disorders/pathology/ physiopathology;Dementia/pathology/physiopathology;Electroencephalography/ methods;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Tomography, X-Ray Computed","Sheorajpanday, R. V.;Marien, P.;Weeren, A. J.;Nagels, G.;Saerens, J.;van Putten, M. J.;De Deyn, P. P.",2013,Apr,10.1097/WNP.0b013e3182767d15,0,
1295,Structural neuroimaging in schizophrenia: From methods to insights to treatments,"Historically, Kraepelin speculated that dementia praecox resulted from damage to the cerebral cortex, most notably the frontal and temporal cortices. It is only recently, however, that tools have been available to test this hypothesis. Now, more than a century later, we know that schizophrenia is a brain disorder. This knowledge comes from critical advances in imaging technology-including computerized axial tomography, magnetic resonance imaging, and diffusion imaging- all of which provide an unprecedented view of neuroanatomical structures, in vivo. Here, we review evidence for structural neuroimaging abnormalities, beginning with evidence for focal brain abnormalities, primarily in gray matter, and proceeding to the quest to identify abnormalities in brain systems and circuits by focusing on damage to white matter connections in the brain. We then review future prospects that need to be explored and pursued in order to translate our current knowledge into an understanding of the neurobiology of schizophrenia, which can then be translated into novel treatments. © 2010 LLS SAS.",,"Shenton, M. E.;Whitford, T. J.;Kubicki, M.",2010,2010,,0,
1296,A review of MRI findings in schizophrenia,"After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described 'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi - 92% of studies reviewed, basal ganglia - 68% of studies reviewed, corpus callosum - 63% of studies reviewed, and thalamus - 42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescen e or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. Future studies will likely benefit from: (1) studying more homogeneous patient groups so that the relationship between MRI findings and clinical symptoms become more meaningful; (2) studying at risk populations such as family members of patients diagnosed with schizophrenia and subjects diagnosed with schizotypal personality disorder in order to define which abnormalities are specific to schizophrenia spectrum disorders, which are the result of epiphenomena such as medication effects and chronic institutionalization, and which are needed for the development of frank psychosis; (3) examining shape differences not detectable from measuring volume alone; (4) applying newer methods such as diffusion tensor imaging to investigate abnormalities in brain connectivity and white matter fiber tracts; and, (5) using methods that analyze brain function (fMRI) and structure simultaneously. © 2001 Elsevier Science Ltd.",,"Shenton, M. E.;Dickey, C. C.;Frumin, M.;McCarley, R. W.",2001,15,,0,
1297,Childhood and current cognitive function in healthy 80-year-olds: A DT-MRI study,"Diffusion tensor MR imaging (DT-MRI) yields information on early pathological changes in white matter of the ageing brain which may correlate with cognitive function. However, because individuals vary in their cognitive ability, a measurement of prior cognition from youth is required to understand fully the significance of MR imaging changes associated with ageing. Here, diffusion tensor parameters and cognitive function were measured in a cohort of 30 older subjects whose cognitive ability was measured at age II and 80. There was a significant correlation between diffusion anisotropy measured in the centrum semiovale at age 80 and mental ability determined at both age II and 80. These novel results suggest, that",,"Shenkin, S. D.;Bastin, M. E.;MacGillivray, T. J.;Deary, I. J.;Starr, J. M.;Wardlaw, J. M.",2003,3,,0,
1298,Assessment of Iron Deposition in the Brain in Frontotemporal Dementia and Its Correlation with Behavioral Traits,"BACKGROUND AND PURPOSE: Brain iron deposition has been implicated as a major culprit in the pathophysiology of neurodegeneration. However, the quantitative assessment of iron in behavioral variant frontotemporal dementia and primary progressive aphasia brains has not been performed, to our knowledge. The aim of our study was to investigate the characteristic iron levels in the frontotemporal dementia subtypes using susceptibility-weighted imaging and report its association with behavioral profiles. MATERIALS AND METHODS: This prospective study included 46 patients with frontotemporal dementia (34 with behavioral variant frontotemporal dementia and 12 with primary progressive aphasia) and 34 age-matched healthy controls. We performed behavioral and neuropsychological assessment in all the subjects. The quantitative iron load was determined on SWI in the superior frontal gyrus and temporal pole, precentral gyrus, basal ganglia, anterior cingulate, frontal white matter, head and body of the hippocampus, red nucleus, substantia nigra, insula, and dentate nucleus. A linear regression analysis was performed to correlate iron content and behavioral scores in patients. RESULTS: The iron content of the bilateral superior frontal and temporal gyri, anterior cingulate, putamen, right hemispheric precentral gyrus, insula, hippocampus, and red nucleus was higher in patients with behavioral variant frontotemporal dementia than in controls. Patients with primary progressive aphasia had increased iron levels in the left superior temporal gyrus. In addition, right superior frontal gyrus iron deposition discriminated behavioral variant frontotemporal dementia from primary progressive aphasia. A strong positive association was found between apathy and iron content in the superior frontal gyrus and disinhibition and iron content in the putamen. CONCLUSIONS: Quantitative assessment of iron deposition with SWI may serve as a new biomarker in the diagnostic work-up of frontotemporal dementia and help distinguish frontotemporal dementia subtypes.",,"Sheelakumari, R.;Kesavadas, C.;Varghese, T.;Sreedharan, R. M.;Thomas, B.;Verghese, J.;Mathuranath, P. S.",2017,Oct,,0,
1299,Application of iodine-123-labeled isopropylamphetamine imaging to the study of dementia,"Forty-seven patients diagnosed as clinically demented were imaged with (123)I isopropylamphetamine (IMP). All of these patients also had a nuclear magnetic resonance (NMR) study. In those patients diagnosed as having senile dementia of the Alzheimer type a bilateral reduction in IMP uptake in the temporo-parieto-occipital region was always seen. The NMR appearances were normal in 64% of these sites. The IMP images of patients with multi-infarct dementia varied from normal to marked focal deficits. There was, however, a much closer agreement between the abnormalities seen on the IMP and NMR images. In alcoholic dementia no focal areas of reduced IMP uptake were seen, although the uptake was generally irregular. In both Korsakoff's psychosis and Huntington's chorea the IMP uptake pattern and the NMR study were normal.",,"Sharp, P.;Gemmell, H.;Cherryman, G.",1986,1986,,0,
1300,Adult-onset MELAS presenting as herpes encephalitis,"Objective: To report an unusual presentation of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) manifested in late life with a clinical picture of herpes simplex encephalitis. Design: Case report. Setting: Clinical neurology department in a tertiary care hospital. Case Description: A 55-year-old woman developed aphasia and delirium during ophthalmic herpes zoster infection treated with oral prednisone and ophthalmic steroids, which was followed by progressive cognitive decline without acute neurologic events for 5 years. At age 60, the patient presented with new onset of seizures, hemiparesis, and hemianopsia. Subsequently she developed cortical blindness, multiple tramautic soft tissue injuries from falls, acute psychosis, and severe dementia with periods of agitation. She died in a nursing home in March 1997, 6 years after initial presentation. Results: Magnetic resonance imaging scan of the brain showed hyperintensity on T(2)-weighted images involving temporal, parietal, and occipital lobes bilaterally as well as mild atrophy of brainstem and cerebellum. Single photon emission computed tomographic imaging showed hypoperfusion of temporal, parietal, and occipital lobes. Results of video electroencephalographic monitoring showed periodic lateralizing epileptiform discharges in temporal and occipital areas. The serum lactate level was normal in May 1996 and elevated in October 1996. The creatine kinase level was elevated with a 100% MM fraction in August 1991 and normal in March 1996. Results of repeated cerebrospinal fluid analyses indicated elevated protein levels. Analysis of DNA was diagnostic of MELAS by mitochondrial DNA point mutation at position 3243. The results of autopsy showed moderate cerebral, cerebellar, and brainstem atrophy with signs of infarction in temporal and parietal lobes bilaterally. Conclusions: The clinical presentation as well as age at onset of MELAS are highly variable. Onset of mitochondrial disorders can be provoked by febrile illness when there is mismatch between energy requirements and availability. In the differential diagnosis of herpes encephalitides, MELAS syndrome should be considered.",,"Sharfstein, S. R.;Gordon, M. F.;Libman, R. D.;Malkin, E. S.",1999,February,,0,
1301,Prediction of Alzheimer's disease using individual structural connectivity networks,"Alzheimer's disease (AD) progressively degrades the brain's gray and white matter. Changes in white matter reflect changes in the brain's structural connectivity pattern. Here, we established individual structural connectivity networks (ISCNs) to distinguish predementia and dementia AD from healthy aging in individual scans. Diffusion tractography was used to construct ISCNs with a fully automated procedure for 21 healthy control subjects (HC), 23 patients with mild cognitive impairment and conversion to AD dementia within 3 years (AD-MCI), and 17 patients with mild AD dementia. Three typical pattern classifiers were used for AD prediction. Patients with AD and AD-MCI were separated from HC with accuracies greater than 95% and 90%, respectively, irrespective of prediction approach and specific fiber properties. Most informative connections involved medial prefrontal, posterior parietal, and insular cortex. Patients with mild AD were separated from those with AD-MCI with an accuracy of approximately 85%. Our finding provides evidence that ISCNs are sensitive to the impact of earliest stages of AD. ISCNs may be useful as a white matter-based imaging biomarker to distinguish healthy aging from AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Anisotropy;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Functional Laterality;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis;Nerve Fibers/pathology;Neural Pathways/ pathology;Neuropsychological Tests;Predictive Value of Tests","Shao, J.;Myers, N.;Yang, Q.;Feng, J.;Plant, C.;Bohm, C.;Forstl, H.;Kurz, A.;Zimmer, C.;Meng, C.;Riedl, V.;Wohlschlager, A.;Sorg, C.",2012,Dec,10.1016/j.neurobiolaging.2012.01.017,0,
1302,A rare form of adult onset leukodystrophy: Orthochromatic leukodystrophy with pigmented glia,"Background: Orthochromatic leukodystrophy with pigmented gila and scavenger cells is a rare leukodystrophy of unknown etiology. This report describes a 42-year-old man with a history of depression, dementia and parkinsonism having the pathological features of orthochromatic leukodystrophy with pigmented glia. Methods: We reviewed the clinical history and pathology of autopsy and brain biopsy material. Results: Imaging revealed bilateral cerebral white matter hypodensities. At autopsy, the brain demonstrated a leukodystrophy affecting predominantly the cerebral hemispheres and characterized by demyelination, and cytoplasmic pigment deposits in oligodendroglia and astrocytes. The pigment had the staining properties of ceroid-lipofuschin and on ultrastructural examination was composed of membrane-bound lipid and electron-dense inclusions which had a fingerprint-like pattern. Similar pigment inclusions were not observed on ultrastructural examination of renal, splenic or hepatic tissue obtained at autopsy. The brain biopsy contained cerebral cortex with sparse subcortical white matter in which a few oligodendroglia and fewer astrocytes at the grey/white junctions showed cytoplasmic pigmentary inclusions identical to those described above. However, due to the paucity of white matter in the specimen a definite diagnosis of orthochromatic leukodystrophy with pigmented glia was not made. Conclusions: The diagnosis of orthochromatic leukodystrophy with pigmented glia and scavenger cells can only be made antemortem if the brain biopsy contains adequate white matter and although a rare condition, it should be considered in the differential diagnosis of an adult onset leukodystrophy.",,"Shannon, P.;Wherrett, J. R.;Nag, S.",1997,May,,0,
1303,[An analysis of regional cerebral blood flows (rCBF) in 120 patients with cerebrovascular disease],"The rCBF in a group of 120 patients with cerebrovascular disease (CVD) diagnosed clinically as well as with CT scans and a group of 120 healthy subjects as controls was measured with the 133Xenon inhalation method. The result showed that the rCBF of the CVD group was significantly lower than that of the control group (P less than 0.01). The tally rate between the rCBF reduction areas and the lesion sites was 85 per cent. The areas of rCBF reduction measured with 133Xenon inhalation were larger than the extents of the lesions shown by CT scans in 47 cases of cerebral infarction. The rCBF reductions of bilateral cerebral hemispheres were found in 16 cases of cerebral infarction. The average hemispheric rCBF obviously decreased in 12 cases of multiple cerebral infarction with dementia, but showed no decrease of rCBF in 18 cases of small focal cerebral infarction.","Adult;Aged;Brain/radionuclide imaging;*Cerebrovascular Circulation;Cerebrovascular Disorders/*physiopathology;Dementia, Multi-Infarct/physiopathology;Female;Humans;Male;Middle Aged;Xenon Radioisotopes","Shang, M. Q.",1991,Feb,,0,
1304,Quantitative morphologic evaluation of white matter in survivors of childhood medulloblastoma,"In survivors of pediatric brain tumors, cranial radiation therapy can cause a debilitating cognitive decline associated with decreased volume in normal-appearing white matter (NAWM). We applied fractal geometry to quantify white matter (WM) integrity in the brain of medulloblastoma survivors. Fractal features of WM were evaluated by indices of fractal dimensions (FDs) of WM intensity and boundary on T(1)-weighted magnetic resonance images. The FD index of WM intensity was calculated by using a fractional Brownian motion model, and the FD index of WM boundary was calculated by using a box-counting method. Fractal features of WM on 116 magnetic resonance images of 58 patients with medulloblastoma were investigated at the start of therapy (Start TX) and approximately 2 years later (After TX). Patients were assigned to one of two groups based on change in NAWM volumes. Fractal features in patients with decreased NAWM volume were significantly greater After TX, whereas those in patients with increased NAWM volumes were not. Multiple linear regression analysis showed that fractal features were strongly correlated with NAWM volumes After TX in patients with decreased NAWM volume. These results demonstrated significant deficit in NAWM integrity and WM density changes in children treated for medulloblastoma. Multiple regression analysis illustrated that deficits in NAWM integrity in these children may partly explain the decrease in NAWM volume. We conclude that fractal geometry can be used to monitor the morphologic effects of neurotoxicity in brain tumor survivors. © 2006 Elsevier Inc. All rights reserved.",,"Shan, Z. Y.;Liu, J. Z.;Glass, J. O.;Gajjar, A.;Li, C. S.;Reddick, W. E.",2006,October,,0,
1305,Cerebral microbleeds as a biomarker in Alzheimer's disease? A review in the field,"Cerebral microbleeds (CMBs) are a marker of small vessel disease, increasingly recognized as being of importance in the Alzheimer's disease (AD) process. CMBs influence in AD, and its longitudinal impact on disease progression is however still unknown. CMBs show several associations with AD across studies, are associated with decreased cerebrospinal fluid amyloid levels and are related with the ApoE 4 allele, as well as other imaging manifestations typical for small vessel disease. CMBs, in addition to other markers of small vessel disease, are important to discover further in order to discern possible AD phenotypes.",,"Shams, S.;Wahlund, L. O.",2016,,10.2217/bmm.15.101,0,
1306,"Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis-the Karolinska Imaging Dementia Study","BACKGROUND AND PURPOSE: Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia. MATERIALS AND METHODS: We analyzed 1504 patients (53% women; mean age, 63 +/- 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded. RESULTS: Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses. CONCLUSIONS: Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia.","Aged;Aged, 80 and over;Brain/pathology;Cerebral Hemorrhage/ epidemiology/etiology/ pathology;Dementia/ pathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Prevalence;Risk Factors","Shams, S.;Martola, J.;Granberg, T.;Li, X.;Shams, M.;Fereshtehnejad, S. M.;Cavallin, L.;Aspelin, P.;Kristoffersen-Wiberg, M.;Wahlund, L. O.",2015,Apr,10.3174/ajnr.A4176,0,
1307,Topography and Determinants of Magnetic Resonance Imaging (MRI)-Visible Perivascular Spaces in a Large Memory Clinic Cohort,"BACKGROUND: Magnetic resonance imaging-visible perivascular spaces (PVS) are related to interstitial fluid clearance pathways (including amyloid-beta) in the brain and are suggested to be a marker of cerebral small vessel disease. We investigated the role, topography, and possible implications of PVS in cognitive impairment. METHODS AND RESULTS: A total of 1504 patients undergoing memory clinic investigation and an associated brain magnetic resonance imaging scan were included in this cross-sectional study. Magnetic resonance images were assessed for markers of small vessel disease. Additionally, 1039 patients had cerebrospinal fluid analysis of amyloid-beta 42, total tau (T-tau), and phosphorylated tau (P-tau); 520 patients had apoE genotyping done. Results were analyzed with generalized linear models. A total of 289 (19%; 95% confidence interval, 17-21) had a high-grade PVS in the centrum semiovale (CSO) and 65 (4%; 95% confidence interval: 3%-5%) in the basal ganglia (BG). Centrum semiovale- and BG-PVS were both associated with high age (P<0.001), hypertension (P<0.001), probable cerebral amyloid angiopathy (P<0.05), moderate-to-severe white matter hyperintensities (P<0.001), cortical superficial siderosis (P<0.001), cerebral microbleeds (P<0.001), and PVS. centrum semiovale-PVS was separately associated with strictly lobar cerebral microbleeds (P=0.057). BG-PVS was associated with strictly deep cerebral microbleeds (P<0.001), lacunes (P<0.001), and vascular dementia (P=0.04). BG-PVS showed a tendency to be associated with high cerebrospinal fluid tau (B=0.002, P=0.04) in the whole cohort and in Alzheimer's disease (B=0.005; P=0.02). No other associations with cerebrospinal fluid or the apoE e4 allele was observed. CONCLUSIONS: Centrum semiovale-PVS and BG-PVS have different underlying etiology, being associated with cerebral amyloid angiopathy and hypertensive vasculopathy, respectively, although a significant overlap between these pathologies is likely to exist.",cerebral microbleed;cerebral small vessel disease;cognitive impairment;magnetic resonance imaging,"Shams, S.;Martola, J.;Charidimou, A.;Larvie, M.;Granberg, T.;Shams, M.;Kristoffersen-Wiberg, M.;Wahlund, L. O.",2017,Sep 22,,0,
1308,Cortical superficial siderosis,"Objective: To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series. Methods: We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients. MRIs were systematically evaluated for presumed marker of small vessel disease: cSS, cerebral microbleeds, enlarged perivascular spaces, white matter hyperintensities, and lacunes. Results: cSS was detected in 40 patients (2.7%; 95% confidence interval [CI] 1.9-3.6); cSS was focal in 33 cases (2.2%; 95% CI 1.5-3.1) and disseminated in 7 (0.5%; 95% CI 0.2-1). Vascular dementia had the highest cSS prevalence (13%; 95% CI 5.4-24.9), followed by Alzheimer disease (5%; 95% CI 3.1-7.5). The most commonly affected area was the occipital lobe (70%; 95% CI 53.5-83.4). cSS was associated with lobar cerebral microbleeds (odds ratio [OR] 7.9; 95% CI 3.4-18.1; p < 0.001), high-degree centrum semiovale perivascular spaces (OR 1.7; 95% CI 1.2-2.6; p 0.008), and white matter hyperintensities (OR 1.5; 95% CI 1.0-2.2; p 0.062). APOE ϵ4/4 genotype was more common in cSS cases compared to those without. CSF β-amyloid 42 was lower in patients with cSS (coefficient -0.09; 95% CI -0.15 to -0.03; p 0.004). Conclusions: Our large series of memory clinic patients provides evidence that cSS is related to cerebrovascular disease and may be a manifestation of severe CAA, even in patients without intracerebral hemorrhage.",Alzheimer disease;brain hemorrhage;controlled study;genetic marker;genotype;hospital;human;major clinical study;memory;multiinfarct dementia;nuclear magnetic resonance imaging;occipital lobe;odds ratio;perivascular space;prevalence;siderosis;vascular amyloidosis;white matter;amyloid beta protein;apolipoprotein E;biological marker;endogenous compound,"Shams, S.;Martola, J.;Charidimou, A.;Cavallin, L.;Granberg, T.;Shams, M.;Forslin, Y.;Aspelin, P.;Kristoffersen-Wiberg, M.;Wahlund, L. O.",2016,,,0,
1309,Cortical superficial siderosis: Prevalence and biomarker profile in a memory clinic population,"OBJECTIVE: To gain further insight into cortical superficial siderosis (cSS), a new hemorrhagic neuroimaging marker of cerebral amyloid angiopathy (CAA), and to investigate the clinical, neuroimaging, genetic, and CSF biomarker profile of cSS in a large, consecutive memory clinic series. METHODS: We included 1,504 memory clinic patients undergoing dementia investigation including a brain MRI in our center. Routine CSF biomarker analysis was performed in 1,039 patients and APOE genotyping in 520 patients. MRIs were systematically evaluated for presumed marker of small vessel disease: cSS, cerebral microbleeds, enlarged perivascular spaces, white matter hyperintensities, and lacunes. RESULTS: cSS was detected in 40 patients (2.7%; 95% confidence interval [CI] 1.9-3.6); cSS was focal in 33 cases (2.2%; 95% CI 1.5-3.1) and disseminated in 7 (0.5%; 95% CI 0.2-1). Vascular dementia had the highest cSS prevalence (13%; 95% CI 5.4-24.9), followed by Alzheimer disease (5%; 95% CI 3.1-7.5). The most commonly affected area was the occipital lobe (70%; 95% CI 53.5-83.4). cSS was associated with lobar cerebral microbleeds (odds ratio [OR] 7.9; 95% CI 3.4-18.1; p < 0.001), high-degree centrum semiovale perivascular spaces (OR 1.7; 95% CI 1.2-2.6; p = 0.008), and white matter hyperintensities (OR 1.5; 95% CI 1.0-2.2; p = 0.062). APOE epsilon4/4 genotype was more common in cSS cases compared to those without. CSF beta-amyloid 42 was lower in patients with cSS (coefficient -0.09; 95% CI -0.15 to -0.03; p = 0.004). CONCLUSIONS: Our large series of memory clinic patients provides evidence that cSS is related to cerebrovascular disease and may be a manifestation of severe CAA, even in patients without intracerebral hemorrhage.",,"Shams, S.;Martola, J.;Charidimou, A.;Cavallin, L.;Granberg, T.;Shams, M.;Forslin, Y.;Aspelin, P.;Kristoffersen-Wiberg, M.;Wahlund, L. O.",2016,Sep 13,10.1212/wnl.0000000000003088,0,
1310,SWI or T2*: which MRI sequence to use in the detection of cerebral microbleeds? The Karolinska Imaging Dementia Study,"BACKGROUND AND PURPOSE: Cerebral microbleeds are thought to have potentially important clinical implications in dementia and stroke. However, the use of both T2* and SWI MR imaging sequences for microbleed detection has complicated the cross-comparison of study results. We aimed to determine the impact of microbleed sequences on microbleed detection and associated clinical parameters. MATERIALS AND METHODS: Patients from our memory clinic (n = 246; 53% female; mean age, 62) prospectively underwent 3T MR imaging, with conventional thick-section T2*, thick-section SWI, and conventional thin-section SWI. Microbleeds were assessed separately on thick-section SWI, thin-section SWI, and T2* by 3 raters, with varying neuroradiologic experience. Clinical and radiologic parameters from the dementia investigation were analyzed in association with the number of microbleeds in negative binomial regression analyses. RESULTS: Prevalence and number of microbleeds were higher on thick-/thin-section SWI (20/21%) compared with T2*(17%). There was no difference in microbleed prevalence/number between thick- and thin-section SWI. Interrater agreement was excellent for all raters and sequences. Univariate comparisons of clinical parameters between patients with and without microbleeds yielded no difference across sequences. In the regression analysis, only minor differences in clinical associations with the number of microbleeds were noted across sequences. CONCLUSIONS: Due to the increased detection of microbleeds, we recommend SWI as the sequence of choice in microbleed detection. Microbleeds and their association with clinical parameters are robust to the effects of varying MR imaging sequences, suggesting that comparison of results across studies is possible, despite differing microbleed sequences.","Aged;Cerebral Hemorrhage/ diagnosis;Cohort Studies;Cross-Sectional Studies;Dementia, Vascular/ diagnosis;Female;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Prospective Studies;Sensitivity and Specificity;Sweden","Shams, S.;Martola, J.;Cavallin, L.;Granberg, T.;Shams, M.;Aspelin, P.;Wahlund, L. O.;Kristoffersen-Wiberg, M.",2015,Jun,10.3174/ajnr.A4248,0,
1311,Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment,"Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid beta (Abeta) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Abeta42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood-brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer's patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Abeta42 in the whole cohort and Alzheimer's disease (p < 0.05). Abeta42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.",,"Shams, S.;Granberg, T.;Martola, J.;Li, X.;Shams, M.;Fereshtehnejad, S. M.;Cavallin, L.;Aspelin, P.;Kristoffersen-Wiberg, M.;Wahlund, L. O.",2016,Mar,10.1177/0271678x15606141,0,
1312,Cerebral microbleeds topography and cerebrospinal fluid biomarkers in cognitive impairment,"Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid beta(Abeta)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Abeta42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer's disease ( P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem ( P < 0.001). There were tendencies for increased Abeta42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds ( P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes ( P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Abeta42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities ( P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.",0 (Amyloid beta-Peptides);0 (Biomarkers);0 (tau Proteins);Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Cerebral Amyloid Angiopathy/pathology;Cerebral Hemorrhage/ diagnosis/diagnostic imaging/pathology;Cognitive Dysfunction/complications/ pathology;Cohort Studies;Humans;Magnetic Resonance Imaging/methods;Memory Disorders/complications/ pathology;tau Proteins/cerebrospinal fluid;Amyloid angiopathy;cerebrospinal fluid biomarkers;cognitive impairment;intracerebral hemorrhage;magnetic resonance imaging,"Shams, S.;Granberg, T.;Martola, J.;Charidimou, A.;Li, X.;Shams, M.;Fereshtehnejad, S. M.;Cavallin, L.;Aspelin, P.;Wiberg-Kristoffersen, M.;Wahlund, L. O.",2017,Mar,,0,1313
1313,Cerebral microbleeds topography and cerebrospinal fluid biomarkers in cognitive impairment,"Cerebral microbleeds, a marker of small vessel disease, are thought to be of importance in cognitive impairment. We aimed to study topographical distribution of cerebral microbleeds, and their involvement in disease pathophysiology, reflected by cerebrospinal fluid biomarkers; 1039 patients undergoing memory investigation underwent lumbar puncture and a brain magnetic resonance imaging scan. Cerebrospinal fluid samples were analyzed for amyloid beta(Abeta)42, total tau(T-tau), tau phosphorylated at threonine 18(P-tau) and cerebrospinal fluid/serum albumin ratios. Magnetic resonance imaging sequences were evaluated for small vessel disease markers, including cerebral microbleeds, white matter hyperintensities and lacunes. Low Abeta42 levels were associated with lobar cerebral microbleeds in the whole cohort and Alzheimer's disease (P < 0.001). High cerebrospinal fluid/serum albumin ratios were seen with increased number of cerebral microbleeds in the brainstem (P < 0.001). There were tendencies for increased Abeta42 levels and decreased Tau levels with deep and infratentorial cerebral microbleeds (P < 0.05). Lobar cerebral microbleeds were associated with white matter hyperintensities and lacunes (P < 0.001). Probable cerebral amyloid angiopathy-related cerebral microbleeds were associated with low Abeta42 levels and lacunes, whereas probable cerebral amyloid angiopathy-unrelated cerebral microbleeds were associated with white matter hyperintensities (P < 0.001). Our findings show that cerebral microbleed distribution is associated with different patterns of cerebrospinal fluid biomarkers, supporting different pathogenesis of deep/infratentorial and lobar cerebral microbleeds.",Amyloid angiopathy;cerebrospinal fluid biomarkers;cognitive impairment;intracerebral hemorrhage;magnetic resonance imaging,"Shams, S.;Granberg, T.;Martola, J.;Charidimou, A.;Li, X.;Shams, M.;Fereshtehnejad, S. M.;Cavallin, L.;Aspelin, P.;Wiberg-Kristoffersen, M.;Wahlund, L. O.",2016,May 13,10.1177/0271678x16649401,0,
1314,"Ankle brachial index, MRI markers and cognition: The Epidemiology of Dementia in Singapore study","BACKGROUND AND AIMS: Previous studies showed an independent association of low ankle-brachial index (ABI) with cognitive impairment. However, the association between low ABI and cognition in the presence of both cerebrovascular disease (CeVD) and neurodegeneration is lacking. We aimed at investigating a) the association of low ABI with markers of CeVD and cortical thickness, and b) whether the association of low ABI with cognition is influenced by these markers. METHODS: Data was drawn from the Epidemiology of Dementia In Singapore (EDIS) study where all participants (n = 832) underwent neuropsychological tests and 3T brain magnetic resonance imaging (MRI) to assess CeVD markers as well as cortical thicknesses. Cognitive function was expressed as a global composite z-score and domain-specific z-scores of a comprehensive neuropsychological battery. RESULTS: Multivariate analyses showed low ABI to be independently associated with intracranial stenosis [odds ratios (OR): 1.51; 95% confidence interval (CI):1.23-1.87] and lacunar infarcts [OR: 1.29; 95% CI: 1.06-1.57]. A low ABI was also independently associated with smaller cortical thickness globally [beta: 0.09; 95% CI: 0.27-0.16] as well as with the limbic [beta: 0.10; 95% CI: 0.03-0.17], temporal [beta: 0.09; 95% CI: 0.02-0.15], parietal [beta: 0.08; 95% CI: 0.02-0.15], and occipital [beta: 0.09; 95% CI: 0.03-0.16] lobes. Low ABI was associated with worse performance in verbal memory [beta: 0.06; 95% CI: 0.01-0.12], which became attenuated in the presence of MRI markers. CONCLUSIONS: A low ABI is associated with MRI markers, and affects cognition in the presence of CeVD and neurodegeneration. Atherosclerosis should be targeted as a potentially modifiable risk factor to prevent cognitive disorders.",Atherosclerosis;Atrophy;Cerebrovascular disease;Cognition,"Shaik, M. A.;Venketasubramanian, N.;Cheng, C. Y.;Wong, T. Y.;Vrooman, H.;Ikram, M. K.;Hilal, S.;Chen, C.",2017,Aug,,0,
1315,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in an Israeli family,"Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of hereditary cerebral microangiopathy, and is caused by over 170 different mutations in the NOTCH3 gene at locus 19p13.1-13.26. We report the first study of familial CADASIL in a 39-year-old Jewish woman and her mother who had died previously. The patient's investigations revealed a normal hemogram with no vascular risk factors or chronic disease. Lumbar puncture was normal. Cranial computed tomography scan revealed bilateral diffuse hypodensities in the subcortical white matter. Cranial magnetic resonance imaging showed hyperintense lesions in the cerebral white matter on T2-weighted images. On electron microscopy, a characteristic granular osmiophilic material was seen in the basement membrane surrounding the pericytes and smooth muscle cells in small-sized and medium-sized vessels. Molecular analysis of the NOTCH3 gene was performed with automatic sequencing of exon 3 and 4 (and intron-exon boundaries) showing a nucleotide c.268C > T substitution, leading to a pathogenic amino acid substitution of p.Arg90Cys, confirming a diagnosis of CADASIL. This mutation was also found in the patient's mother. Although the exact prevalence of CADASIL is not known, this disorder has been reported worldwide, and now including Jews, with a genotype and clinical phenotype similar to that in other ethnic groups. © 2011 Shahien et al.",,"Shahien, R.;Bianchi, S.;Bowirrat, A.",2011,2011,,0,
1316,Longitudinal diffusion changes in prodromal and early HD: Evidence of white-matter tract deterioration,"Introduction: Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). Methods: As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1–5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. Results: Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. Conclusions: This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460–1477, 2017. © 2017 Wiley Periodicals, Inc.",adult;article;controlled study;cross-sectional study;diffusion tensor imaging;diffusion weighted imaging;female;follow up;human;Huntington chorea;image processing;longitudinal study;major clinical study;male;middle aged;neuroimaging;nuclear magnetic resonance scanner;premotor cortex;primary motor cortex;primary somatosensory cortex;priority journal;prodromal symptom;putamen;white matter,"Shaffer, J. J.;Ghayoor, A.;Long, J. D.;Kim, R. E. Y.;Lourens, S.;O'Donnell, L. J.;Westin, C. F.;Rathi, Y.;Magnotta, V.;Paulsen, J. S.;Johnson, H. J.",2017,,10.1002/hbm.23465,0,
1317,L-2-hydroxyglutaric aciduria: A report of six cases and review of the literature,"L-2-hydroxyglutaric aciduria is a rare and novel autosomal recessive inherited neurometabolic disorder. Since Its first description by Duran in 1980, less than 100 cases have so far been reported. Occurring mostly in childhood, it is characterized by slowly progressive neurological dysfunction with cerebellar ataxia, pyramidal signs, intellectual decline, seizure, and extrapyramidal symptoms. MRI scanning is highly characteristic and screening for organic acid (L-2-hydroxyglutaric acid) in urine, serum, and cerebrospinal fluid is diagnostic. We investigated six Iranian children, aged 4,14,16, and 16 years, (the last one had two affected brothers and both of them died of similar illness at the ages of 20 and 22), by urinary organic acids assay and MRI scanning with suspicion of this rare disorder. Symptoms were suspicious for one of the leukoencephalopathies accompanied by macrocephaly. Affected cases were evaluated because of mild to moderate psychomotor retardation and regression. Head circumferences were above 2 standard deviations. Urine levels of L-2-hydroxyglutaric acid were strongly increased. MRI scanning of the brain showed hyperintense signal on T2W images of the subcortical white matter and basal ganglia in all of them. Because of its inheritance pattern (autosomal recessive) and the high rate of consanguineous marriages in Iran, the prevalence of this disorder might be high among the mentally-handicapped patients, especially those with macrocephaly. Therefore, this entity should be considered in the differential diagnosis of mentally-retarded patients with macrocephly.",,"Shafeghati, Y.;Vakili, G.;Entezari, A.",2006,April,,0,
1318,In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T,"BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations. RESULTS: Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13-1.62). APOE4 presence was associated with a greater tortuosity ratio (rho = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant. CONCLUSIONS: Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.",,"Shaaban, C. E.;Aizenstein, H. J.;Jorgensen, D. R.;MacCloud, R. L.;Meckes, N. A.;Erickson, K. I.;Glynn, N. W.;Mettenburg, J.;Guralnik, J.;Newman, A. B.;Ibrahim, T. S.;Laurienti, P. J.;Vallejo, A. N.;Rosano, C.;Group, Life Study",2017,Oct,,0,
1319,The ticking of the epigenetic clock: Antipsychotic drugs in old age,"Background: Exposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear. CNS small vessel disease (SVD) is a well-known age-related risk factor for strokes, dementia, and sudden death, which may constitute the initial CVAE-predisposing pathology. Therefore, we propose the two strikes CVAE paradigm, in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities may be directly proportional with the CVAE risk. To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4). Since microRNA-29 has shown efficacy against the same malignancies and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 upregulation, which in turn facilitates the development of SVD. Aim: To assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk. Method: We conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity and may be relevant for CVAE. Conclusion: Upregulated microRNA-29 silences the expression of 18 genes connected with capillary stability, engendering a major vulnerability for SVD (first strike) which in turn increases the risk for CVAE after exposure to APDs (second strike).",biological marker;melatonin receptor;microRNA 29;neuroleptic agent;sirtuin;vasculotropin;aged;article;brain ischemia;cerebrovascular accident;dementia;DNA methylation;epigenetics;gene expression regulation;gene silencing;human;malignant neoplastic disease;metabolic disorder;microvascular ischemia;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;sudden cardiac death;wound healing,"Sfera, A.;Osorio, C.;Inderias, L.;Cummings, M.",2016,,10.3389/fendo.2016.00122,0,
1320,"MRI correlates of episodic memory in Alzheimer's disease, mild cognitive impairment, and healthy aging","Episodic memory is a core feature of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Impaired episodic memory in AD results from the dysfunction of an integrated network and involves both gray and white matter pathologies. We explored the neural correlates of episodic memory in AD, MCI and healthy aging by correlating a measure of episodic memory with hippocampal volume and fractional anisotropy (FA) and mean diffusivity (MD) of the cingulum and fornix. Episodic memory was associated with hippocampal volume and MD of the cingulum and fornix. In contrast, there were fewer significant associations between episodic memory and FA. These findings support a relationship between episodic memory and hippocampal circuitry, and suggest that MD is a more sensitive marker of decreased white matter integrity in the study of AD and MCI than FA. Furthermore, MD was significantly associated with hippocampal volume, indicating that white matter pathology is not completely independent of gray matter pathology. However, the pattern of diffusivity differences in AD and MCI implies a more complex pathology than simply Wallerian degeneration.","Aged;Aged, 80 and over;Alzheimer Disease/*complications;Analysis of Variance;Anisotropy;Cognition Disorders/*complications;Diffusion Magnetic Resonance Imaging;Factor Analysis, Statistical;Female;Functional Laterality;*Geriatric Assessment;Hippocampus/physiopathology;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Memory Disorders/*etiology/*pathology;Mental Recall/*physiology;Neuropsychological Tests","Sexton, C. E.;Mackay, C. E.;Lonie, J. A.;Bastin, M. E.;Terriere, E.;O'Carroll, R. E.;Ebmeier, K. P.",2010,Oct 30,10.1016/j.pscychresns.2010.07.005,0,
1321,"Association of plasma total homocysteine levels with subclinical brain injury: Cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study","Background: Elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of dementia and stroke, but it is uncertain whether the mediating mechanisms are predominantly cellular, vascular, or both. Objective: To evaluate the relationship between tHcy levels and findings at brain magnetic resonance imaging (MRI) in a community-based sample. Design: Our sample comprised 1965 participants in the Framingham Offspring Study (1050 women; mean [SD] age, 62 [9] years) who were free of clinical stroke, dementia, or other neurologic disease affecting brain MRI and for whom at least 1 measurement of plasma tHcy level (1991-2001) and a brain MRI (1999-2002) were available. We used multivariate regression analysis to relate initial (1991-1995) and concurrent (1998-2001) plasma tHcy levels to total cerebral brain volume and lobar volumes as measures of neuronal loss and atrophy and to the presence or absence of silent brain infarcts and extensive white matter hyperintensity (log-white matter intensity ≥1 SD above the age-adjusted mean) as separate measures of vascular injury. Results: Mean total cerebral brain volume was 78%. At MRI, 218 participants had silent brain infarcts and 250 demonstrated extensive white matter hyperintensity. Participants with a plasma tHcy level in the highest age-(-0.37%, P=.01) or sex-specific (-0.48%, P<.001) quartile had smaller total cerebral brain volumes compared with participants with lower tHcy levels. Initial tHcy levels were associated with a higher prevalence of silent brain infarct (relative risk, 1.5; 95% confidence interval, 1.1-2.1; P=.02) and concurrent tHcy levels, with smaller frontal (-0.14%, P=.001) and temporal lobar (-0.10%, P=.04) volumes. Prevalence of extensive white matter hyperintensity did not differ according to initial or concurrent plasma tHcy levels (relative risk, both 1.0; 95% confidence interval, 0.7-1.4 and 0.8-1.4, respectively). Conclusions: Higher plasma tHcy levels are associated with smaller brain volume and the presence of silent brain infarcts at MRI, even in healthy, middle-aged adults. Thus, both cellular and vascular mechanisms may underlie the association of plasma tHcy level with brain aging, as reflected by the effects on both subclinical and overt disease. ©2008 American Medical Association. All rights reserved.",,"Seshadri, S.;Wolf, P. A.;Beiser, A. S.;Selhub, J.;Au, R.;Jacques, P. F.;Yoshita, M.;Rosenberg, I. H.;D'Agostino, R. B.;DeCarli, C.",2008,May,,0,
1322,Genetic correlates of brain aging on MRI and cognitive test measures: A genome-wide association and linkage analysis in the framingham study,"Background: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999-2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. Results: The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10(-6)) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10(-8)) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). Conclusion: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies. © 2007 Seshadri et al; licensee BioMed Central Ltd.",,"Seshadri, S.;de Stefano, A. L.;Au, R.;Massaro, J. M.;Beiser, A. S.;Kelly-Hayes, M.;Kase, C. S.;D'Agostino, R. B.;de Carli, C.;Atwood, L. D.;Wolf, P. A.",2007,,,0,
1323,Differentiating shunt-responsive normal pressure hydrocephalus from alzheimer disease and normal aging: Pilot study using automated mri brain tissue segmentation,"Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from preshunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33% relative to HC characterized AD (P\0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3% accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.",,"Serulle, Y.;Rusinek, H.;Kirov, I. I.;Milch, H.;Fieremans, E.;Baxter, A. B.;McMenamy, J.;Jain, R.;Wisoff, J.;Golomb, J.;Gonen, O.;George, A. E.",2014,,,0,
1324,Apolipoproteins E and C1 and brain morphology in memory impaired elders,"Previous research has shown that polymorphisms of the apolipoproteins E (APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.",,"Serra-Grabulosa, J. M.;Salgado-Pineda, P.;Junqué, C.;Solé-Padullés, C.;Moral, P.;López-Alomar, A.;López, T.;López-Guillén, A.;Bargalló, N.;Mercader, J. M.;Clemente, I. C.;Bartrés-Faz, D.",2003,April,,0,
1325,Cognitive reserve and the risk for Alzheimer's disease: a longitudinal study,"This study investigates how cognitive reserve (CR) interacts with neurodegeneration (quantified by medial temporal atrophy, MTA) and macroscopic white matter lesions (WMLs) in delaying the conversion from amnestic mild cognitive impairment to Alzheimer's disease (AD). Forty-two amnestic mild cognitive impairment patients were consecutively recruited. They underwent magnetic resonance imaging and a comprehensive questionnaire to classify them as individuals with low or high CR. Patients were then clinically followed-up for 2 years. The patients' risk for conversion to AD because of CR was estimated by controlling for cognitive efficiency, MTA, and WMLs at baseline. Global cognition was the best predictor of conversion to AD in low CR patients. Conversely, in high CR patients only, WMLs (but not MTA) highly contributed in increasing the risk for conversion to AD. In conclusion, CR interacts with both patients' cognitive features and WMLs in modulating the impact of AD pathology. This seems relevant for clinical prognosis and therapeutic strategies.",Aged;Alzheimer Disease/ pathology/ psychology;Atrophy;Brain/pathology/physiopathology;Cognition;Cohort Studies;Disease Progression;Female;Follow-Up Studies;Forecasting;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/pathology/psychology;Nerve Degeneration/pathology;Neuropsychological Tests;Prognosis;Risk;Surveys and Questionnaires;Temporal Lobe/pathology;Time Factors;White Matter/pathology,"Serra, L.;Musicco, M.;Cercignani, M.;Torso, M.;Spano, B.;Mastropasqua, C.;Giulietti, G.;Marra, C.;Bruno, G.;Koch, G.;Caltagirone, C.;Bozzali, M.",2015,Feb,10.1016/j.neurobiolaging.2014.10.010,0,
1326,Grey and white matter changes at different stages of Alzheimer's disease,"This study investigates abnormalities of grey (GM) and white matter (WM) in Alzheimer's disease (AD), by modeling the AD pathological process as a continuous course between normal aging and fully developed dementia, with amnesic mild cognitive impairment (aMCI) as an intermediate stage. All subjects (9 AD, 16 aMCI patients, and 13 healthy controls) underwent a full neuropsychological assessment and an MRI examination at 3 Tesla, including a volumetric scan and diffusion tensor (DT)-MRI. The volumes were processed to perform a voxel-based morphometric analysis of GM and WM volume, while DT-MRI data were analyzed using tract based spatial statistics, to estimate changes in fractional anisotropy and mean diffusivity data. GM and WM volume and mean diffusivity and fractional anisotropy were compared across the three groups, and their correlation with cognitive functions was investigated. While AD presented a pattern of widespread GM atrophy, tissue loss was more subtle in patients with aMCI. WM atrophy was mainly located in the temporal lobe, but evidence of WM microscopic damage, assessed by DT-MRI, was also observable in the thalamic radiations and in the corpus callosum. Memory and executive functions correlated with either GM volume or fractional anisotropy in fronto-temporal areas. In conclusion, this study shows a comprehensive assessment of the brain tissue damage across AD evolution, providing insights on different pathophysiological mechanisms (GM atrophy, Wallerian degeneration, and brain disconnection) and their possible association with clinical aspects of cognitive decline.","Aged;Alzheimer Disease/*pathology/psychology;Cerebral Cortex/*pathology;*Disease Progression;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology","Serra, L.;Cercignani, M.;Lenzi, D.;Perri, R.;Fadda, L.;Caltagirone, C.;Macaluso, E.;Bozzali, M.",2010,,10.3233/jad-2010-1223,0,
1327,White matter damage along the uncinate fasciculus contributes to cognitive decline in AD and DLB,"This study investigates the patho-physiological implications of the uncinate fasciculus (UF) in the two most common forms of dementia, namely Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Forty-five consecutive patients diagnosed with either probable AD or DLB, and 16 individuals with amnesic mild cognitive impairment (a-MCI) were investigated using diffusion tensor MRI. Thirteen healthy subjects (HS) were also studied as controls. In each subject, the UF was bilaterally reconstructed by probabilistic tractography. From each UF, macroscopic volume and correspondent fractional anisotropy (FA) (an index of microscopic white matter integrity) were derived for the whole tract, and for the frontal and temporal portion of the UF. No significant between-group volumetric differences were found. In contrast, FA values from the UF were reduced bilaterally in patients with dementia (either AD or DLB) compared to HS. In addition, patients with AD showed reduced FA values compared to those with a-MCI. No significant FA difference was found between AD and DLB patients, nor between a-MCI and HS. Finally, in all patients, UF FA values were associated with neuropsychological scores at tests exploring memory and executive functions. This study indicates that the UF is remarkably damaged in patients at the stage of dementia, independently from the diagnostic form. Moreover, this UF damage seems to be driven by temporal involvement in AD, for which a prodromal stage (a-MCI) is defined.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/physiopathology/psychology;Brain/*pathology/physiopathology;Cognition Disorders/*pathology/physiopathology/psychology;Cohort Studies;Female;Humans;Lewy Body Disease/*pathology/physiopathology/psychology;Male;Middle Aged;Neural Pathways/*pathology/physiopathology;Wallerian Degeneration/*pathology/physiopathology","Serra, L.;Cercignani, M.;Basile, B.;Spano, B.;Perri, R.;Fadda, L.;Marra, C.;Giubilei, F.;Caltagirone, C.;Bozzali, M.",2012,Mar,,0,
1328,Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment,"BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.","Aged;Aged, 80 and over;Amnesia/*diagnosis/etiology/physiopathology;Brain/blood supply/*pathology/physiopathology;Cerebrovascular Disorders/complications/*diagnosis/physiopathology;Cognition Disorders/*diagnosis/etiology/physiopathology;Cohort Studies;Dementia/diagnosis/etiology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Mass Screening;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Risk Factors","Sepe-Monti, M.;Pantano, P.;Vanacore, N.;De Carolis, A.;Bianchi, V.;Antonini, G.;Guidoni, S. V.;Giubilei, F.",2007,Jun,10.1111/j.1600-0404.2007.00825.x,0,
1329,Prevalence of Brain Microbleeds in Alzheimer Disease: A Systematic Review and Meta-Analysis on the Influence of Neuroimaging Techniques,"BACKGROUND AND PURPOSE: The literature on the prevalence of Alzheimer disease-associated cerebral microbleeds assessed with MR imaging shows considerable heterogeneity in terms of imaging techniques and parameters. Our aim was to perform a meta-analysis of the role of imaging techniques, including image acquisition, field strength and scanner type, and clinical and demographic factors on the reported prevalence of microbleeds in Alzheimer disease. MATERIALS AND METHODS: The prevalence of microbleeds was examined with respect to a priori-selected moderating variables via meta-analytic tools of literature reports. RESULTS: Fourteen unique studies providing 15 microbleed prevalence rates met the selection criteria for inclusion. The aggregate prevalence of microbleeds was 24% (95% CI, 19%-28%). Scan (SWI = 40%, gradient echo = 18%, EPI = 19%) and field strength (slope = 0.39; standard error = 15, P < .01) influenced the prevalence of microbleeds. The associations between microbleeds and age, sex, and global cognitive status were not significant. After updating the literature, the aggregate prevalence remained in the 95% CI range. CONCLUSIONS: Imaging technique and field strength are strongly associated with the prevalence of microbleeds over the global aggregate. Standardized imaging protocols for identification of microbleeds are recommended to minimize confounds.",,"Sepehry, A. A.;Lang, D.;Hsiung, G. Y.;Rauscher, A.",2016,Feb,10.3174/ajnr.A4525,0,
1330,"Cardiovascular risk factors cause cortical thinning in cognitively impaired patients: Relationships among cardiovascular risk factors, white matter hyperintensities, and cortical atrophy","Cardiovascular risk factors are associated with cognitive impairments. However, the effects of cardiovascular risk factors on the topography of cortical thinning have not yet been studied in patients with mild cognitive impairment (MCI) or dementia. Thus, we aimed to evaluate the topography of cortical thinning related to cardiovascular risk factors and the relationships among cardiovascular risk factors, white matter hyperintensities (WMH), and cortical atrophy. Participants included 226 patients with Alzheimer disease or subcortical vascular dementia and 135 patients with amnestic MCI or subcortical vascular MCI. We automatically measured the volume of WMH and cortical thickness. Hypertension was associated with cortical thinning in the frontal and perisylvian regions, and cortical thinning related to diabetes mellitus (DM) occurred in the frontal region. In path analyses, hypertension accounted for 0.04 of the frontal thinning with the mediation of WMH and 0.16 without the mediation of WMH. In case of DM, it accounted for 0.02 of the frontal thinning with the mediation of WMH and 0.13 without the mediation of WMH. Hypertension and DM predominantly affected frontal thinning both with and without the mediation of WMH, where the effects without the mediation of WMH were greater than those with the mediation of WMH. © 2012 by Lippincott Williams & Wilkins.",adult;aged;Alzheimer disease;article;brain cortex atrophy;brain region;brain size;cardiovascular risk;cognitive defect;diabetes mellitus;diabetic patient;female;frontal lobe;human;hyperlipidemia;hypertension;image processing;inferior frontal gyrus;major clinical study;male;mild cognitive impairment;multiinfarct dementia;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;posterior cingulate;priority journal;suprasylvian gyrus;temporal lobe;white matter,"Seo, S. W.;Lee, J. M.;Im, K.;Park, J. S.;Kim, S. H.;Kim, S. T.;Ahn, J. H.;Kim, M. J.;Kim, G. H.;Kim, J. H.;Roh, J. H.;Cheong, H. K.;Na, D. L.",2012,,,0,
1331,Cortical thinning related to periventricular and deep white matter hyperintensities,"Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer's disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction. © 2012 Elsevier Inc.",adult;aged;Alzheimer disease;amnesia;article;brain cortex atrophy;brain region;brain size;deep white matter hyperintensity;disease association;female;frontal cortex;human;major clinical study;male;mild cognitive impairment;multiinfarct dementia;nervous system parameters;neuropsychological test;nuclear magnetic resonance imaging;periventricular white matter hyperintensity;priority journal;suprasylvian gyrus;topography;white matter,"Seo, S. W.;Lee, J. M.;Im, K.;Park, J. S.;Kim, S. H.;Kim, S. T.;Ahn, H. J.;Chin, J.;Cheong, H. K.;Weiner, M. W.;Na, D. L.",2012,,,0,
1332,Neurochemical alterations of the entorhinal cortex in amnestic mild cognitive impairment (aMCI): A three-year follow-up study,"The neurochemical alterations in the entorhinal cortex have not yet been measured, even though the entorhinal cortex is the earliest involved brain region in aMCI. In this study, we investigated whether brain regions including the entorhinal cortex would show early involvement of neurochemical abnormalities in aMCI, and whether magnetic resonance spectroscopy (MRS) abnormalities might be a predictive marker of conversion of aMCI to Alzheimer's disease (AD). MRS was performed on 13 aMCI patients and 11 patients with no cognitive impairment (NCI). Localizing voxels were placed within the entorhinal cortex, hippocampus, posterior cingulate gyrus, and occipital white matter in the dominant hemisphere. N-acetyl aspartate/creatinine (NAA/Cr) ratios in the entorhinal cortex were significantly lower in aMCI patients than in NCI subjects. After a three-year follow-up, seven aMCI patients converted to AD and six remained stable. Baseline NAA/Cr ratios of entorhinal cortex were decreased in converters, compared to NCI. Our study suggested the entorhinal cortex is the earliest site that is subject to neurochemical alteration in aMCI patients, and baseline MRS metabolite ratios in the entorhinal cortex can be a marker for predicting conversion of aMCI to AD. © 2011.",creatinine;n acetylaspartic acid;neurotransmitter;aged;Alzheimer disease;amnesia;article;brain region;clinical article;controlled study;disease marker;entorhinal cortex;female;follow up;hippocampus;human;male;mental performance;mild cognitive impairment;neurochemistry;neuroimaging;neuropathology;neuropsychological test;nuclear magnetic resonance imaging;posterior cingulate;prediction;priority journal;white matter,"Seo, S. W.;Lee, J. H.;Jang, S. M.;Kim, S. T.;Chin, J.;Kim, G. H.;Kim, J. H.;Roh, J. H.;Kim, M. J.;Kim, S. H.;Na, D. L.",2012,,,0,
1333,Clinical significance of microbleeds in subcortical vascular dementia,"BACKGROUND AND PURPOSE - Despite many studies investigating the association between the ischemic changes and cognitive impairment in subcortical vascular dementia (SVaD), few studies correlated cognitive impairment with microbleeds (MBs) frequently seen in SVaD. METHODS - Participants consisted of 86 patients with SVaD who fulfilled the criteria proposed by Erkinjuntti et al. RESULTS - MBs occurred in 73 of 86 (84.9%) patients with SVaD. MBs were most commonly distributed in the cortex, and the cortical MBs were most pronounced in the temporoparietal area. A multiple regression showed that the number of cerebral MB was an independent predictor of cognitive impairment in multiple domains and the severity of dementia even after controlling confounding factors such as age, education, ischemic severity, and number of lacunes. CONCLUSION - These results indicate that cerebral MB is one of the important factors that cause cognitive impairments in SVaD. © 2007 American Heart Association, Inc.",aged;article;bleeding;brain cortex;cognitive defect;disease association;disease severity;female;human;major clinical study;male;multiinfarct dementia;multiple regression;nuclear magnetic resonance imaging;priority journal,"Seo, S. W.;Lee, B. H.;Kim, E. J.;Chin, J.;Cho, Y. S.;Yoon, U.;Na, D. L.",2007,,,0,
1334,Measurements of lenticulostriate arteries using 7T MRI: new imaging markers for subcortical vascular dementia,"Recent studies have demonstrated that ultra-high resolution MRA imaging using 7 Tessla (T) MRI can be employed to noninvasively visualize the lenticulostriate arteries (LSA) that supply the basal ganglia and internal capsule. Subcortical vascular dementia (SVaD) is believed to involve these regions from an early stage. We investigated whether LSA abnormalities measured by 7T MRA correlate with MRI ischemia markers and neuropsychological/motor deficits. A total of 24 subjects (12 with SVaD, 12 normal controls (NC)) were imaged with 3T and 7T MRIs. We assessed the severity of white matter hyperintensities (WMH) and the number of lacunes and microbleeds (MB) by visually inspecting images obtained from conventional 3T MRI. We also analyzed three-dimensional models of the measured LSAs obtained from 7T MRI. Compared to the NC, the SVaD subjects had fewer branches of LSAs and greater radii of LSAs. The number of branches was correlated with the number of lacunes. The number of branches was correlated with the delayed recall scores on Rey's Complex Figure Test (RCFT). While not quite reaching statistical significance, the immediate recall, recognition scores on the RCFT, recognition scores on the Seoul Verbal Learning Test, and the word and color readings of Stroop trended in the direction of correlation with the number of branches, as well as with the extrapyramidal scores. Our findings suggest that LSA imaging using 7T MRI might be a potent candidate for the detection of SVaD.","Aged;Basal Ganglia/ blood supply/pathology;Cerebral Arteries/ pathology;Dementia, Vascular/ diagnosis;Female;Humans;Imaging, Three-Dimensional;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales","Seo, S. W.;Kang, C. K.;Kim, S. H.;Yoon, D. S.;Liao, W.;Worz, S.;Rohr, K.;Kim, Y. B.;Na, D. L.;Cho, Z. H.",2012,Nov 15,10.1016/j.jns.2012.05.032,0,
1335,Cortical thinning in vascular mild cognitive impairment and vascular dementia of subcortical type,"BACKGROUND AND PURPOSE: Amnestic mild cognitive impairment (MCI) is known to be a preclinical stage of Alzheimer's disease (AD). Similarly, MCI associated with small-vessel disease (svMCI), might be a forme froste of subcortical vascular dementia (SVaD). Patterns of cortical thinning in addition to the ischemia rating on MRI may further elucidate the clinical characteristics and pathogenesis of SVaD and svMCI. We tried to determine if svMCI differs from SVaD in the distribution of cortical atrophy, which may help understand the hierarchy between svMCI and SVaD and possibly also how svMCI evolves into SVaD. METHODS: Twenty patients with SVaD, 34 patients with svMCI, 115 patients with AD, and 96 individuals with normal-cognition (NC) were imaged with magnetic resonance imaging (MRI) including 3-dimensional volumetric images for cortical thickness analysis across the entire brain. RESULTS: Compared to NC, svMCI patients showed cortical thinning in inferior frontal and orbitofrontal gyri, anterior cingulate, insula, superior temporal gyrus, and lingual gyrus, while cortical thinning in SVaD patients involved all these areas plus dorsolateral prefrontal and temporal cortices. CONCLUSION: Our findings suggest the presence of hierarchy between svMCI and SVaD, and that the cognitive decline from svMCI to SVaD is associated with lesions in dorsolateral prefrontal and temporal cortices.","Age Factors;Aged;Cerebral Cortex/ pathology;Cerebrovascular Disorders/ pathology;Cognition Disorders/ pathology;Cross-Sectional Studies;Data Interpretation, Statistical;Dementia, Vascular/ pathology;Educational Status;Female;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Observer Variation;Organ Size;Sex Factors","Seo, S. W.;Ahn, J.;Yoon, U.;Im, K.;Lee, J. M.;Tae Kim, S.;Ahn, H. J.;Chin, J.;Jeong, Y.;Na, D. L.",2010,Jan,10.1111/j.1552-6569.2008.00293.x,0,
1336,Vascular dementia clinically resembling Creutzfeldt-Jakob disease,"An autopsy case of vascular dementia, clinically resembling Creutzfeldt-Jakob disease, is reported. A 74-year-old woman showed progressive dementia, transient myoclonus of the right upper arm, diffuse periodic synchronous discharges on electroencephalography, and brain atrophy on computed tomography. The duration of the illness was 17 months. Neuropathologic findings were numerous small necrotic foci in the middle and lower layers of the cerebral cortex, myelin pallor of the cerebral white matter, and fibrous thickening of the arterial and arteriolar walls in the cerebrum and cerebellum (both cortex and white matter). Vascular dementia was diagnosed. On the basis of these features, it is considered that such neuropathologic changes caused Creutzfeldt-Jakob-like symptoms, such as dementia and periodic synchronous discharges.",aged;arteriole;article;autopsy;brain artery;brain atrophy;brain cortex;brain necrosis;case report;cerebellum;clinical feature;Creutzfeldt Jakob disease;dementia;disease duration;electroencephalogram;female;human;multiinfarct dementia;myelin deficiency;myoclonus;priority journal;white matter,"Seno, H.;Ishino, H.;Inagaki, T.;Lijima, M.;Kikumoto, O.;Yoshinaga, J.;Matsuura, H.;Tachiyama, Y.",1997,,,0,
1337,"The Dementia and Disability Project in Thai Elderly: rational, design, methodology and early results","BACKGROUND: A strong inverse relationship of functional limitation and socioeconomic status has been established in western ageing society. Functional limitation can be related to chronic diseases, disuse, cognitive decline, and ageing. Among chronic diseases in the Thai population, cerebrovascular diseases, diabetes, and arthritis are common. These factors are known to contribute to disability and poor quality of life in the elder population. Neuropsychiatric problems, cognitive decline, dementia, and cultural issues in elderly people also can alter the quality of life of the elderly. METHODS: The Dementia and Disability Project in Thai Elderly (DDP) aims at comprehensively assessing community dwelling Thai elderly to understand the relationship between disability and motor function, neuropsychiatric symptoms, cognitive function, and chronic diseases. The DDP is the first study to look at the prevalence and etiology of dementia and of mild cognitive impairment (MCI) in Thai elders and to explore the relationship of cognition, disability, small vessel diseases and cortical degeneration with neuroimaging in Thai elderly people. 1998 Thai elders were screened in 2004-2006 and diagnosed as having MCI or dementia. 223 elders with MCI or dementia and cognitively normal elderly had brain magnetic resonance imaging (MRI) or at baseline. 319 elders from the 3 groups had blood tests to investigate the risks and possible etiologies of dementia including genotyping at baseline. RESULTS: The mean age of elders in this study is 69.51(SD=6.71, min=60, max=95) years. 689(34.9%) are men and 1284(65.1%) are women. Mean body weight was 58.36(SD=11.20) kgs. The regression model reveals that performance on gait and balance and serum triglyceride predicts activity of daily living performance (adjusted r2 = 0.280, f=2.644, p=0.003). The majority of abnormal gait in Thai elders was lower level gait disturbance. Only 1.5% (29/1952) had highest level gait disorders. 39.5% of 1964 subjects were free of chronic diseases. Treatment gap (indicating those who have untreated or inadequate treatment) of diabetes mellitus and hypertension in Thai elders in this study was 37% and 55.5% respectively. 62.6% of Thai elders have ApoE3E3 allele. Prevalence of positive ApoE4 gene in this study is 22.85%. 38.6% of Thai elders who had MRI brain study have moderate to severe white matter lesions. CONCLUSION: The large and comprehensive set of measurements in DDP allows a wide-ranging explanation of the functional and clinical features to be investigated in relation to white matter lesions or cortical atrophy of the brain in Thai elderly population. An almost 2 year follow up was made available to those with MCI and dementia and some of the cognitively normal elderly. The longitudinal design will provide great understanding of the possible contributors to disability in the elderly and to the progression of cognitive decline in Thai elders.","Aged;Aged, 80 and over;Dementia/ complications/diagnosis/ epidemiology;Disabled Persons;Female;Humans;Male;Mental Disorders/epidemiology/etiology;Middle Aged;Mild Cognitive Impairment/ epidemiology/ etiology;Neuropsychological Tests;Regression Analysis;Residence Characteristics;Thailand/epidemiology;Triglycerides/blood","Senanarong, V.;Harnphadungkit, K.;Poungvarin, N.;Vannasaeng, S.;Chongwisal, S.;Chakorn, T.;Jamjumrus, P.;Raksthaput, A.;Chaichanettee, S.;Aoonkaew, N.;Udompunthurak, S.;Doody, R. S.;Cummings, J. L.",2013,,10.1186/1471-2377-13-3,0,
1338,Cerebral White Matter Lesions as a Clinically Relevant Intermediate Target of Cerebrovascular Prevention,,arterial stiffness;attention;blood pressure regulation;brain blood flow;cardiovascular risk;cognition;cognitive defect;computer assisted tomography;dementia;executive function;heart failure;heart stroke volume;hemodynamics;human;hypertension;hypotension;leukoaraiosis;note;nuclear magnetic resonance imaging;perfusion;priority journal;pulse pressure;risk assessment;white matter;white matter change;white matter lesion,"Semplicini, A.",2015,,,0,
1339,Clinical and neuroimaging findings in a family with CADASIL associated to C475T mutation,"Introduction. The term CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) refers to an autosomal dominant hereditary arteriopathy of the brain that is characterised by headache, recurring strokes and progressive cognitive deterioration. We report the case of another family with CADASIL and emphasise the importance of a genetic study in its diagnosis. Case report. A 62-year-old female patient with repeating lacunar strokes, subcortical dementia and a family history of dementia and strokes. Neuroimaging studies conducted on the patient and her siblings showed signs of leukoencephalopathy and lacunar infarctions. The ultrastructural study of the biopsy performed on a sample of the patient's skin, which included five dermal vessels, did not show any electron-dense deposits. The genetic study revealed the presence of mutation C475T in exon 4 of NOTCH3. Conclusions. The possible presence of CADASIL must be suspected in patients with symptoms of cerebrovascular disease or dementia who present characteristic alterations in the magnetic resonance brain scan, especially when there is a compatible family history. The first choice diagnostic procedure must be a genetic study.",cytidine;Notch3 receptor;thymidine;adult;article;autosomal dominant disorder;CADASIL;case report;cell ultrastructure;clinical feature;cognitive defect;dementia;diagnostic accuracy;diagnostic imaging;differential diagnosis;exon;family history;female;gene mutation;genetic analysis;headache;human;human tissue;image analysis;leukoencephalopathy;multiinfarct dementia;neuroimaging;nuclear magnetic resonance imaging;recurrent disease;sibling;skin biopsy;cerebrovascular accident;symptom,"Sempere, Á P.;Pérez-Tur, J.;García-Barragán, N.;Sellés, J.;Medrano, V.;Mola, S.",2004,,,0,
1340,"Hypogonadotropic hypogonadism and cerebellar ataxia: Detailed phenotypic characterization of a large, extended kindred","Although the co-occurrence of cerebellar ataxia and hypogonadism has been recognized for close to 100 yr, cases of Gordon Holmes syndrome are quite rare. This report describes the largest kindred characterized to date. The parents of the three affected siblings are first cousins, suggesting that the disease was inherited as an autosomal recessive trait. The siblings' initial evaluation was notable for low serum levels of sex steroids and gonadotropins (consistent with hypogonadotropic hypogonadism), progressive ataxia, and dementia. Extended treatment with physiological doses of pulsatile GnRH failed to stimulate a gonadotropin response. Brain imaging revealed volume loss in the cerebellum, with extensive abnormalities in the cerebral white matter. This unique family suggests that a common genetic mechanism is responsible for the syndrome of progressive hypogonadotropism and cerebellar ataxia.",,"Seminara, S. B.;Acierno Jr, J. S.;Abdulwahid, N. A.;Crowley Jr, W. F.;Margolin, D. H.",2002,2002,,0,
1341,Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke,"Cerebral microvascular angiopathy (MVA) is associated with clinical vascular risk factors and is characterised by histological changes, including thickening of the walls of arterial vessels and dilatation of the Virchow-Robin spaces (VRS). We have previously described two novel biomarkers of MVA based on magnetic resonance imaging (MRI), VRS dilatation and abnormalities in the transfer of systolic arterial pulsation to the ventricular CSF, which occur as a result of decreased cerebral arterial compliance. These are associated with vascular dementia and treatment-resistant late onset depression. We studied a group of normal subjects at risk of cerebrovascular disease to determine if these biomarkers are present in patients who have no evidence of symptomatic vascular disease. We studied 31 subjects, 16 with three or more vascular risk factors and 15 with one or less significant risk factors. We measured arterial blood flow and CSF flow in the cerebral aqueduct, white matter lesion load, and the distribution and number of VRS. There were significant differences in CSF pulsatility and in VRS in the basal ganglia between the two groups, but no differences in white matter lesion load. We conclude that asymptomatic subjects at risk of stroke have MRI evidence of MVA before white matter lesions become apparent.","Aged;Biomarkers;Cerebral Arteries/pathology;Dementia, Vascular/complications/pathology;Diagnostic Imaging/methods;Female;Humans;Male;Microcirculation;Microscopy, Phase-Contrast;Middle Aged;Risk Factors;Stroke/ diagnosis/pathology;Vascular Diseases/ diagnosis/therapy","Selvarajah, J.;Scott, M.;Stivaros, S.;Hulme, S.;Georgiou, R.;Rothwell, N.;Tyrrell, P.;Jackson, A.",2009,Apr,10.1007/s00330-008-1202-8,0,
1342,Hippocampal complex atrophy in poststroke and mild cognitive impairment,"To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-beta concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-beta concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.","Adult;Aged;Aged, 80 and over;Alzheimer Disease;Amyloid beta-Peptides/cerebrospinal fluid;Atrophy;Cerebrovascular Disorders/pathology/psychology;Executive Function;Female;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Memory;Mental Recall;Middle Aged;Mild Cognitive Impairment/*pathology/*psychology;Neuropsychological Tests;Psychomotor Performance;Reaction Time;Stroke/*pathology/*psychology;White Matter/pathology;tau Proteins/cerebrospinal fluid","Selnes, P.;Grambaite, R.;Rincon, M.;Bjornerud, A.;Gjerstad, L.;Hessen, E.;Auning, E.;Johansen, K.;Almdahl, I. S.;Due-Tonnessen, P.;Vegge, K.;Bjelke, B.;Fladby, T.",2015,Nov,10.1038/jcbfm.2015.110,0,
1343,White matter imaging changes in subjective and mild cognitive impairment,"Background: To determine whether white matter (WM) memory network changes accompany early cognitive impairment and whether these changes represent early, pathologically independent axonal affection, we combined WM diffusion tensor imaging and cortical morphometric measurements of normal control subjects, patients with only subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). Methods: We included 66 patients with SCI or MCI and 21 control subjects from a university-hospital-based memory clinic in a cross-sectional study. Morphometric analysis was performed in FreeSurfer, and Tract-Based Spatial Statistics was used for analysis of diffusion tensor imaging-derived WM fractional anisotropy, radial diffusivity (DR), and mean diffusivity (MD). Relationships between WM measures and stage were assessed with whole-brain voxelwise statistics and on a region-of-interest basis, with subsequent correction for cortical atrophy. Results: In SCI patients, as compared with control subjects, there were widespread changes in DR and MD. No significant differences in thickness could be demonstrated. In MCI patients, as compared with control subjects, there were widespread changes in DR, MD, and fractional anisotropy; the precuneal and inferior parietal cortices were thinner; and the hippocampus was smaller. Multiple logistic regression analysis eliminated morphometry as an explanatory variable in favor of DR/MD for all regions of interest, except in the precuneus, where both thickness and DR/MD were significant explanatory variables. Conclusions: WM tract degeneration is prominent in SCI and MCI patients, and is at least in part independent of overlying gray matter atrophy. © 2012 The Alzheimer's Association. All rights reserved.",,"Selnes, P.;Fjell, A. M.;Gjerstad, L.;Bjornerud, A.;Wallin, A.;Due-Tonnessen, P.;Grambaite, R.;Stenset, V.;Fladby, T.",2012,October,,0,
1344,Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid,"BACKGROUND: Alzheimer's disease (AD) and cerebrovascular disease (CVD) including chronic small vessel disease of the brain (SVD) are the most frequent causes of dementia. AD is associated with metabolism of amyloid precursor protein (APP) and low levels of amyloid-beta peptide (Abeta) X-42 in the cerebrospinal fluid (CSF). CVD and SVD are established risk factors for AD, brain white matter lesions (WML) are established surrogate markers for SVD and are also associated with reduced CSF AbetaX-42.A cohort survey was performed to examine whether SVD or acute CVD affects APP metabolism and to explore a potential association between WML and APP metabolism in two groups; cognitively impaired patients, subjective and mild (SCI and MCI) and stroke patients. Through measurements of CSF APP metabolite levels in patients with a wide range of WML volumes, this study aimed to determine how SVD influences APP metabolism. METHODS: Sixty-three patients were included: 37 with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI) without stroke, and 26 after acute stroke. Chronic and acute WML volume and infarct volume were determined by magnetic resonance imaging (MRI) post-scan processing, and CSF levels of alpha- and beta-cleaved soluble APP (sAPP-alpha and sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42) were determined. The Mann-Whitney test was used to compare the patient groups. Chronic and acute WML volumes, infarct volume, age, and sex were used as predictors for CSF biomarker levels in linear regression analysis. RESULTS: CSF levels of sAPP-alpha and sAPP-beta were strongly correlated (r = 0.95, p < 0.001) and lower levels of these biomarkers were found in the stroke group than in the SCI/MCI group; median sAPP-alpha 499.5 vs. 698.0 ng/mL (p < 0.001), sAPP-beta 258.0 vs. 329.0 ng/mL (p < 0.005). CSF levels of sAPP-alpha, sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42 were inversely correlated with chronic WML volume (p </= 0.005; p </= 0.01; p </= 0.01; p </= 0.05; p </= 0.05 respectively), but not with acute WML or infarct volumes. CONCLUSIONS: Lower CSF levels of sAPP-alpha and sAPP-beta in the stroke group than in the SCI/MCI group and an inverse correlation with chronic WML indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests that APP axonal transport or metabolism may be affected in SVD of the brain.",,"Selnes, P.;Blennow, K.;Zetterberg, H.;Grambaite, R.;Rosengren, L.;Johnsen, L.;Stenset, V.;Fladby, T.",2010,,10.1186/1743-8454-7-10,0,
1345,The cognitive pattern of vascular dementia and its assessment,"Prevailing definitions of dementia are based on the Alzheimer disease (AD) model, which places major emphasis on memory impairment. In other dementias, such as vascular dementia (VaD), several other cognitive dysfunctions predominate over the memory disorder. The cognitive pattern changes according to the type of VaD. In multi-infarct dementia (MID), cortical lesions may cause loss of instrumental functions manifested by aphasia, amnesia, apraxia, or agnosia. Language in MID patients has shorter phrase length, restricted lexical variability, simplified syntax, and low verbal fluency; dysarthria or mechanical impairment of speech with abnormal pitch, melody, or articulation rate also occur. The latter are rare in degenerative dementias. Compared with AD, patients with MID demonstrate superior performance on verbal learning and memory, better delayed recall, and lower rates of forgetting, intrusions, and false positives. Subcortical ischemic dementia, subcortical hemorrhages, or single subcortical strategic infarcts frequently impair executive functions, attention, and speed of information processing; anterograde memory is generally less impaired than in AD patients. The two main problems of batteries used for evaluation of dementia such as those recommended by CERAD (verbal fluency test, a brief naming test such as the Modified Boston Naming Test, free recall of a word list, with immediate and delayed recall, followed by a recognition task of the same words, and line drawings of figures), as well as the Mini-Mental State Examination (MMSE), are (1) their strong emphasis on memory, temporal and spatial orientation, calculation, language, and constructional praxis, and (2) their failure to assess executive functions. Simple tests of executive function include the Trail Making Test, the Wisconsin Card Sorting Test, and the EXIT-25. A simple and effective test is the CLOX, an executive variation of the clock-drawing task. Depressive symptoms and other psychiatric disturbances are particularly common in VaD and become sources of cognitive and functional disability. Several questionnaires assess the neuropsychiatric manifestations of dementia including the Neuro-Psychiatric Inventory (NPI), the BEHAVE-AD test, the Cohen-Mansfield Scale, and the CERAD Behavioral Rating Scale for Dementia. Finally, development of dementia after a stroke may represent true VaD in patients with intact cognition before the stroke, or AD + CVD when the dementia occurs in patients that already had memory problems before the ictus. The diagnosis of VaD is a challenging clinical problem that encompasses the fields of medicine, neurology, psychiatry, and psychology. © 2004 Elsevier Inc. All rights reserved.",adult;agnosia;Alzheimer disease;amnesia;anterograde amnesia;aphasia;apraxia;article;attention;brain function;brain hemorrhage;brain infarction;brain injury;brain ischemia;calculation;case report;cognition;cognitive defect;depression;differential diagnosis;disease classification;disease model;dizziness;drawing;dysarthria;facial nerve paralysis;female;human;language ability;language disability;learning;medical assessment;memory consolidation;memory disorder;mental disease;Mini Mental State Examination;multiinfarct dementia;neuropsychiatry;neuropsychology;nuclear magnetic resonance imaging;pitch;priority journal;psychologic assessment;psychologic test;questionnaire;rating scale;recall;spatial orientation;speech articulation;speech disorder;cerebrovascular accident;symptom;faintness;task performance;time perception;verbal behavior;visual impairment;Wisconsin Card Sorting Test;word recognition,"Sellal, F.;Wolff, V.;Marescaux, C.",2004,,,0,
1346,HIV encephalopathy due to drug resistance despite 2-year suppression of HIV viremia by cART,"A 57-year-old man presented with subacute progression of cognitive impairment (MMSE 22/30). He had been diagnosed as AIDS two years before and taking atazanavir, abacavir, and lamivudine. HIV RNA of plasma had been negative. On admission, HIV RNA was 4,700 copy/ml and 5,200 copy/ml in plasma and in cerebrospinal fluid respectively, suggesting treatment failure of cART. The brain magnetic resonance imaging showed high intensity areas in the white matter of the both frontal lobes and brain stem. The drug-resistance test revealed the resistance of lamivudine and abacavir. We introduced the CNS penetration effectiveness (CPE) score to evaluate the drug penetration of HIV drugs. As the former regimen had low points (7 points), we optimized the regimen to raltegravir, zidovudine, and darunavir/ritonavir (scoring 10 points). His cognitive function improved as normal (MMSE 30/30) in 2 weeks and HIV-RNA became undetectable both in plasma and CSF in a month. In spite of the cognitive improvement, the white matter hyperintensity expanded. To rule out malignant lymphoma or glioblastoma, the brain biopsy was performed from the right frontal lobe. It revealed microglial hyperplasia and diffuse perivascular infiltration by CD8+/CD4- lymphocytes. No malignant cells were found and the polymerase chain reaction analyses excluded other viruses. Considering the drug penetration to the central nervous system is important for treating HIV encephalopathy.",,"Sekiya, H.;Kawamoto, M.;Togo, M.;Yoshimura, H.;Imai, Y.;Kohara, N.",2014,2014,,0,
1347,MR imaging and localized proton MR spectroscopy in late infantile neuronal ceroid lipofuscinosis,"PURPOSE: Late juvenile neuronal ceroid lipofuscinosis (NCL) is a lysosomal neurodegenerative disorder caused by the accumulation of lipopigment in neurons. Our purpose was to characterize the MR imaging and spectroscopic findings in three children with late infantile NCL. METHODS: Three children with late infantile NCL and three age-matched control subjects were examined by MR imaging and by localized MR spectroscopy using echo times of 135 and 5. Normalized peak integral values were calculated for N- acetylaspartate (NAA), choline, creatine, myo-inositol, and glutamate/glutamine. RESULTS: MR imaging revealed volume loss of the CNS, most prominently in the cerebellum. The T2-weighted images showed a hypointense thalamus and hyperintense periventricular white matter. Proton MR spectra revealed progressive changes, with a reduction of NAA and an increase of myo-inositol and glutamate/glutamine. In long-standing late infantile NCL, myoinositol became the most prominent resonance. Lactate was not detectable. CONCLUSION: MR imaging in combination with proton MR spectroscopy can facilitate the diagnosis of late infantile NCL and help to differentiate NCL from other neurometabolic disorders, such as mitochondrial or peroxisomal encephalopathies.",,"Seitz, D.;Grodd, W.;Schwab, A.;Seeger, U.;Klose, U.;Nägele, T.",1998,1998,,0,
1348,Case of carbon monoxide poisoning with delayed encephalopathy assessed by magnetic resonance imaging,"A 21-year-old man attempted suicide by burning charcoal in a car for more than one day and was admitted to a regional hospital. On admission, his blood carboxyhemoglobin concentration was 4.4%. The patient was transferred to our emergency department because of suspected carbon monoxide poisoning. Hyperbaric oxygen therapy (HBO) was performed 5 times over 3 days. Fluid-attenuation inversion recovery (FLAIR) and diffusion-weighted (DWI) magnetic resonance imaging (MRI) performed on day 3 showed high signal-intensity lesions in the cerebral white matter. Additional HBO was performed once per day until day 16. Wecheler Memory Scale-Reviced (WMS-R) and Mini-Mental State Examination (MMSE) performed on day 17 showed his cognitive impairment. He gradually recovered the cognitive function and was discharged from the hospital without neurological sequelae on day 49. Delayed encephalopathy after acute carbon monoxide poisoning with dementia, mental impairment, and psychosis is a serious complication. Hyperintensity in FLAIR and DWI MRI predicts delayed encephalopathy and indicates cellular edema and demyelination of the white matter. One of the risk factors is prolonged carbon monoxide exposure. This case suggests that the patient, who was exposed to carbon monoxide for many hours, was at a high risk of delayed encephalopathy despite the low blood carboxyhemoglobin concentration and therefore must be monitored using MRI.",,"Seino, K.;Hayashida, A.;Iseki, K.",2013,Mar,,0,
1349,Magnetization transfer ratio relates to cognitive impairment in normal elderly,"Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38-86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.",,"Seiler, S.;Pirpamer, L.;Hofer, E.;Duering, M.;Jouvent, E.;Fazekas, F.;Mangin, J. F.;Chabriat, H.;Dichgans, M.;Ropele, S.;Schmidt, R.",2014,,10.3389/fnagi.2014.00263,0,
1350,Lower magnetization transfer ratio in the forceps minor is associated with poorer gait velocity in older adults,"Background and Purpose: Gait disturbances in the elderly are disabling and a major public health issue but are poorly understood. In this multimodal MR imaging study, we used 2 voxel-based analysis methods to assess the voxelwise relationship of magnetization transfer ratio and white matter hyperintensity location with gait velocity in older adults. MATERIALS AND METHODS: We assessed 230 community-dwelling participants of the Austrian Stroke Prevention Family Study. Every participant underwent 3T MR imaging, including magnetization transfer imaging. Voxel-based magnetization transfer ratio-symptom mapping correlated the white matter magnetization transfer ratio of each voxel with gait velocity. To assess a possible relationship between white matter hyperintensity location and gait velocity, we applied voxel-based lesion-symptom mapping. RESULTS: We found a significant association between the magnetization transfer ratio within the forceps minor and gait velocity (β = 0.134; 95% CI, 0.011-0.258; P =.033), independent of demographics, general physical performance, vascular risk factors, and brain volume. White matter hyperintensities did not significantly change this association. CONCLUSIONS: Our study provides new evidence for the importance of magnetization transfer ratio changes in gait disturbances at an older age, particularly in the forceps minor. The histopathologic basis of these findings is yet to be determined.",adult;brain size;cardiovascular risk;cerebrovascular accident;forceps;gait;human;major clinical study;nuclear magnetic resonance imaging;physical performance;prevention study;symptom;velocity;white matter,"Seiler, S.;Pirpamer, L.;Gesierich, B.;Hofer, E.;Duering, M.;Pinter, D.;Jouvent, E.;Fazekas, F.;Mangin, J. F.;Chabriat, H.;Ropele, S.;Schmidt, R.",2017,,10.3174/ajnr.A5036,0,
1351,Vascular cognitive impairment - An ill-defined concept with the need to define its vascular component,"New guidelines for the diagnosis of vascular cognitive impairment (VCI) represent an important step in the definition of this clinical entity. These guidelines still remain vague in the definition of vascular brain lesions causing cognitive decline, because longitudinal correlative imaging studies are still scarce. In this review we explore which abnormalities are likely to contribute to VCI based on a proven vascular etiology, fast progression and their incidence or progression being related to cognitive decline. Among focal changes visible on standard MRI these features apply for coalescent white matter changes. The evidence for lacunes and microbleeds is much less convincing. Microstructural alterations in normal appearing brain tissue which can be detected by new MRI techniques such as magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and high resolution MR appear to better correlate with cognitive decline, but the etiology of these changes and their histopathological correlates is still incompletely understood as is their evolution over time. New multimodal image processing such as voxel-based lesion-symptom mapping (VLSM) or combinations of DTI and voxel-based analysis will allow to allocate the lesion patterns that show the greatest covariance with clinical outcome. Such data and more longitudinal correlative data on lacunes and microbleeds will increase our pathophysiologic understanding of VCI including the interplay with primary degenerative processes and will lead to refinement of current VCI criteria. © 2012 Elsevier B.V.",,"Seiler, S.;Cavalieri, M.;Schmidt, R.",2012,15,,0,
1352,Cerebrovascular disease and cognition in older adults,"The well-established association between advanced age, cerebrovascular pathology, and cognitive decline is receiving greater attention as the population attains new levels of longevity. This chapter will provide an overview of vascular anatomy and age-related cerebrovascular disorders and diseases, including stroke and degenerative dementia. The cognitive and functional sequellae of these cerebrovascular disorders will also be described in detail. Throughout this review, we will emphasize topics that have been relatively underrepresented in the literature, including age-related diseases of the cerebral small vessels, nuanced characterization of cognitive impairment associated with insidious small-vessel vascular dementia, and the real-life functional consequences of cerebrovascular changes in older adults.",article;atherosclerosis;blood brain barrier;capillary;cerebral artery disease;cerebrovascular accident;cerebrovascular disease;cognition;cognitive defect;endothelial dysfunction;episodic memory;executive function;great blood vessel;heart disease;heredity;human;lacunar stroke;middle cerebral artery;multiinfarct dementia;nuclear magnetic resonance imaging;pathological anatomy;posterior cerebral artery;priority journal;semantics;vascular amyloidosis;white matter injury;working memory,"Seidel, G. A.;Giovannetti, T.;Libon, D. J.",2012,,,0,
1353,Neurobrucellosis presenting as leukoencephalopathy: the role of cytotoxic T lymphocytes,"A 65-year-old man developed a leukoencephalopathy associated with neurobrucellosis. The disease followed a 15-month progressive course with neurologic symptoms, and magnetic resonance imaging revealed bilateral symmetrical T2 signal hyperintensities in the white matter. Biopsy of the cerebral cortex and white matter was significant for nongranulomatous meningoencephalitis with reactive microgliosis and astrogliosis. The inflammatory infiltrate was predominantly composed of T lymphocytes, including numerous cytotoxic T cells. There was no evidence of significant myelin destruction. No organisms were detected microscopically, but elevated immunoglobulin G titers to Brucella were found in the cerebrospinal fluid. An abscess formed at the biopsy site, and Brucella melitensis was cultured from abscess contents. Neurobrucellosis is difficult to diagnose outside endemic regions and is associated with leukoencephalopathy-like pathology. Cytotoxic T lymphocytes and microglia activation play an immunopathogenic role in this rare disease.",,"Seidel, G.;Pardo, C. A.;Newman-Toker, D.;Olivi, A.;Eberhart, C. G.",2003,Sep,,0,
1354,The impact of reference region on the variance of estimated change in pet amyloid standard uptake value ratios measured longitudinally in summit and acction,"Background: Longitudinal changes of brain amyloid burden are now routinely assessed in multicenter clinical treatment trials in Alzheimer's disease (AD) using positron emission tomography (PET). The small rate of change and the variance in quantitative measures has fueled intense interest in optimizing methodology to improve the reliability of serial longitudinal assessments. We assessed the impact of different reference regions employed in calculating standard uptake value ratios (SUVr) measured serially in two Phase 2 AD immunotherapy studies - ACCTION and SUMMIT. Methods: F18 Florbetapir PET scans were obtained at screening, weeks 50, 78, 104, or at the end of treatment/placebo or after early termination. A standardized volume of interest template was applied to spatially normalized image volumes for calculation of the composite cortical SUVr using four different reference regions; cerebellar grey, whole cerebellum, pons and subcortical white matter. Percent change from baseline was calculated for each subject (ACCTION n=115, SUMMIT n=130). Results: For the ACCTION trial, baseline to one year follow-up demonstrated in placebo average % SUVr +/- SD one year changes of -0.37 +/- 9.4% and 0.61 +/- 4.0%, and for 10 ug treated subjects, -4.29 +/- 7.8% and 0.22 +/- 3.9% for SUVr reference regions of cerebellar grey and subcortical white matter, respectively. For the SUMMIT trial, baseline to one year follow-up demonstrated in placebo average % SUVr one year changes of 1.96 +/- 8.2% and 2.81 +/- 6.8%, and for treated subjects, 1.08 +/- 9.6% and 2.50 +/- 7.2%, for SUVr reference regions of cerebellar grey and subcortical white matter, respectively. Conclusions: Consistent with other data sets placebo subjects demonstrate a small annual increase in composite SUVr of 1-3 %. Percent change in SUVrs obtained using a white matter reference region demonstrate lower variance; approximately 40- 60% less between subject variability than cerebellar reference regions. This reduced variance may allow a better demonstration of small changes in brain amyloid in participants. However, all potential causes of the reduced variability should be considered in justifying and interpreting the impact of different reference regions.",pet animal;human;white matter;positron emission tomography;follow up;brain;pons;cerebellum;methodology;screening;immunotherapy;reliability;Alzheimer disease;amyloid;placebo,"Seibyl, J. P.;Barret, O.;Ketter, N.;Novak, G. P.;Brashear, H. R.;Liu, E.;Di, J.;Marek, K.",2015,,,0,
1355,Neuroanatomical correlates of olfactory loss in normal aged subjects,"In non-demented older persons, smell dysfunction, measured premortem, has been associated with postmortem brain degeneration similar to that of Alzheimer's disease. We hypothesized that distinct measures of gray and white matter integrity evaluated through magnetic resonance imaging (MRI) techniques could detect degenerative changes associated with age-related olfactory dysfunction. High-resolution T1-weighted images and diffusion-tensor images (DTI) of 30 clinically healthy subjects aged 51-77 were acquired with a 3-Tesla MRI scanner. Odor identification performance was assessed by means of the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT scores correlated with right amygdalar volume and bilateral perirhinal and entorhinal cortices gray matter volume. Olfactory performance also correlated with postcentral gyrus cortical thickness and with fractional anisotropy and mean diffusivity levels in the splenium of the corpus callosum and the superior longitudinal fasciculi. Our results suggest that age-related olfactory loss is accompanied by diffuse degenerative changes that might correspond to the preclinical stages of neurodegenerative processes.","Aged;Anisotropy;Brain Mapping;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/physiology;Neuroanatomy;Neuropsychological Tests;Olfaction Disorders/ pathology;Olfactory Pathways/ pathology;Smell/ physiology;Verbal Learning/physiology","Segura, B.;Baggio, H. C.;Solana, E.;Palacios, E. M.;Vendrell, P.;Bargallo, N.;Junque, C.",2013,Jun 1,10.1016/j.bbr.2013.02.025,0,
1356,Diffusion anisotropy in cerebral white matter lesion,"Diffusion MRI studies were performed on 14 patients with diffuse high-signal lesions of the cerebral white matter on T(2)-weighted MR images. There were two patients with adrenoleukodystrophy, four with dentato-rubro-pallido-luysian atrophy, three with familial spastic paraplegia, two with myotonic dystrophy and three with dementia of unknown origin. In addition, a patient with of Sanfilippo disease and one of the three patients who exhibited dementia of unknown origin were also found to be low-signal in the cerebral cortex T(2)-weighted MR images. In every case except the last two, diffusion-weighted MR images yielded significantly higher apparent diffusion coefficients perpendicular to nerve fibers in the frontal white matter and the corpus callosum than in the normal controls. The lesions displayed increased diffusion anisotropy, calculated as the ratio of the diffusion coefficient perpendicular to the nerve fibers to the diffusion coefficient parallel to the nerve fibers, i.e., diffusion anisotropy was lost in the white matter, suggesting a demyelinating process in the lesion. In the last two cases, on the other hand, the diffusion coefficient and diffusion anisotropy were within normal range. The white matter lesions in these cases were thought to represent degeneration secondary to the cortical involvement. Thus, it was confirmed that diffusion-weighted MR images, unlike T(2)-weighted MR images, were confirmed to allow differentiation between at least two types of white matter lesions.",,"Segawa, F.;Kishibayashi, J.;Kamada, K.;Sunohara, N.;Kinoshita, M.",1994,1994,,0,
1357,Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia,"Background: Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear. Objective: To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex. Design: A bvFTD cohort study. Setting: University hospital dementia clinic. Participants: Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n=15), 1 (n=15), or 2 to 3 (n=15) age and sex matched to each other and to 45 healthy controls. Main Outcome Measures: Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls. Results: Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. ACDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers. Conclusions: Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury. ©2008 American Medical Association. All rights reserved.",adult;aged;article;brain atrophy;brain region;controlled study;disease severity;female;frontotemporal dementia;gray matter;human;limbic cortex;major clinical study;male;nuclear magnetic resonance imaging;priority journal;rating scale;scoring system;white matter,"Seeley, W. W.;Crawford, R.;Rascovsky, K.;Kramer, J. H.;Weiner, M.;Miller, B. L.;Gorno-Tempini, M. L.",2008,,,0,
1358,Lower microstructural integrity of brain white matter is related to higher mortality,"OBJECTIVE: To investigate the association of cerebral white matter microstructural integrity with mortality. METHODS: We included 4,294 individuals, free from stroke and dementia (mean age 63.6 years, 44% male) from the population-based Rotterdam Study (2006-2011). Diffusion-MRI was used to assess the microstructural integrity of the white matter, both globally and for specific white matter tracts. Fractional anisotropy and mean diffusivity were the measures used to quantify white matter integrity. All-cause mortality and cause-specific mortality was recorded with a median follow-up time of 5.4 and 4.6 years, respectively. Cox regression models, adjusted for age, sex, APOE epsilon4 allele carriership, cardiovascular risk factors, and macrostructural MRI changes, were used to estimate hazard ratios. RESULTS: During the follow-up time, 216 participants (5.0%) died of all causes, 31 (0.7%) of cardiovascular causes, and 102 individuals (2.4%) died of noncardiovascular causes. Each SD decrease in fractional anisotropy and each SD increase in mean diffusivity was associated with a 1.37-fold (95% confidence interval: 1.20-1.57) and a 1.49-fold (95% confidence interval: 1.28-1.75) higher hazard of all-cause mortality, respectively. The associations were more prominent with cardiovascular mortality than with noncardiovascular mortality. In tract-specific analyses, we observed that association tracts were more prominently related to mortality. CONCLUSIONS: Our findings suggest that impairments in cerebral white matter, even at early stages, are not limited to adverse brain outcomes and they are related to mortality, especially from cardiovascular causes.",,"Sedaghat, S.;Cremers, L. G.;de Groot, M.;Hofman, A.;van der Lugt, A.;Niessen, W. J.;Franco, O. H.;Dehghan, A.;Ikram, M. A.;Vernooij, M. W.",2016,Aug 30,10.1212/wnl.0000000000003032,0,
1359,"Evidence for a detrimental relationship between hypertension history, prospective memory, and prefrontal cortex white matter in cognitively normal older adults","Hypertension affects many older adults and is associated with impaired neural and cognitive functioning. We investigated whether a history of hypertension was associated with impairments to prospective memory, which refers to the ability to remember to perform delayed intentions, such as remembering to take medication. Thirty-two cognitively normal older adult participants with or without a history of hypertension (self-reported) performed two laboratory prospective memory tasks, one that relied more strongly on executive control (nonfocal prospective memory) and one that relied more strongly on spontaneous memory retrieval processes (focal prospective memory). We observed hypertension-related impairments for nonfocal, but not focal, prospective memory. To complement our behavioral approach, we conducted a retrospective analysis of available structural magnetic resonance imaging data. Lower white matter volume estimates in the anterior prefrontal cortex were associated with lower nonfocal prospective memory and with a history of hypertension. A history of hypertension may be associated with worsened executive control and lower prefrontal white matter volume. The translational implication is that individuals who must remember to take antihypertensive medications and to monitor their blood pressure at home may be impaired in the executive control process that helps to support these prospective memory behaviors.","Aged;Aged, 80 and over;Analysis of Variance;Cognition Disorders/ complications;Dementia/ complications;Female;Humans;Hypertension/ complications;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory, Episodic;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Prefrontal Cortex/ pathology;Semantics","Scullin, M. K.;Gordon, B. A.;Shelton, J. T.;Lee, J. H.;Head, D.;McDaniel, M. A.",2013,Jun,10.3758/s13415-013-0152-z,0,
1360,"Relationship among diffusion tensor imaging, EEG activity, and cognitive status in mild cognitive impairment and Alzheimer's disease patients","Magnetic resonance (MR) diffusion tensor imaging (DTI) can detect microstructural alterations by means of fractional anisotropy (FA) in patients with dementia, also in relation to cognitive status. The present study aimed at investigating the possible relation among white matter damage in DTI, quantitative electroencephalography (EEG) spectral power, and cognitive status in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients. Forty-seven subjects (8 moderate AD, 18 mild AD, 12 MCI, and 9 healthy controls) underwent brain MR, neuropsychological evaluation, and resting EEG recording. A progressive increase of EEG delta and theta spectral power was observed from controls to patients, mainly in more anterior areas, with a parallel widespread decrease of beta power. Moreover, a progressive decrease of FA from controls to patients in frontal areas and in the corpus callosum (genu) was observed. Correlation analyses indicated convergence among EEG rhythms changes, DTI values, and cognitive status mainly over anterior areas. The decrease of FA values and EEG spectral power changes might represent markers of neurodegenerative dysfunction, possibly preceding macrostructural atrophy.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ physiopathology/psychology;Cognition/physiology;Cognition Disorders/diagnosis/physiopathology/psychology;Diffusion Tensor Imaging/methods;Electroencephalography/methods;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/ physiopathology/psychology;Neuropsychological Tests;Single-Blind Method","Scrascia, F.;Curcio, G.;Ursini, F.;Trotta, L.;Quintiliani, L.;Migliore, S.;Altamura, C.;Pitocco, F.;Altavilla, R.;Melgari, J. M.;Quattrocchi, C. C.;Vernieri, F.",2014,,10.3233/jad-130788,0,
1361,Independent value added by diffusion MRI for prediction of cognitive function in older adults,"The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI) provides independent information about baseline level or change in executive function (EF) or memory (MEM) in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study from phases GO and 2 (2009-2015). ADNI participants included were diagnosed as cognitively normal (n = 46), early mild cognitive impairment (MCI) (n = 48), late MCI (n = 29), and dementia (n = 39) at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD) and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed.",Dti;Dementia;Executive function;Mild cognitive impairment;White matter integrity,"Scott, J. A.;Tosun, D.;Braskie, M. N.;Maillard, P.;Thompson, P. M.;Weiner, M.;DeCarli, C.;Carmichael, O. T.;Adni",2017,,,0,
1362,Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly,"In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Abeta1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.",,"Scott, J. A.;Braskie, M. N.;Tosun, D.;Thompson, P. M.;Weiner, M.;DeCarli, C.;Carmichael, O. T.",2015,,10.3389/fnagi.2015.00221,0,
1363,Cerebral amyloid is associated with greater white-matter hyperintensity accrual in cognitively normal older adults,"Cross-sectional studies show that elevated cerebral amyloid is associated with greater white-matter hyperintensity (WMH) burden in cognitively normal (CN) older adults. However, the relative time courses of amyloid and WMH accrual are unclear. To address this, we tested the associations between known WMH correlates-age, hypertension, and amyloid-with WMH accrual rate. We used brain magnetic resonance imaging to measure WMH change in 112 CN Alzheimer's Disease Neuroimaging Initiative (GO/2) participants over a 2-year period. A linear mixed effects model assessed baseline cerebrospinal fluid amyloid beta (Abeta) 1-42, hypertension, age, and their interactions, as predictors of greater WMH accrual. Greater amyloid burden was associated with greater WMH accrual over time. Those with hypertension showed a stronger association between greater amyloid burden and WMH accrual rate. Greater age was not significantly associated with greater WMH accrual in this model. Although the direction of the relationship cannot be tested in this model, CN individuals harboring cerebral amyloid had greater accrual of WMH over a 2-year period after accounting for hypertension and age. Impaired amyloid clearance and cerebral small vessel disease may both underlie the more rapid emergence of WM lesions. The role of cerebral amyloid burden in white-matter injury should thus be considered as a relevant factor when WMHs are detected clinically.",Adni;Amyloid;Flair;Hypertension;Mri;Normal aging,"Scott, J. A.;Braskie, M. N.;Tosun, D.;Maillard, P.;Thompson, P. M.;Weiner, M.;DeCarli, C.;Carmichael, O. T.",2016,Aug 24,10.1016/j.neurobiolaging.2016.08.014,0,
1364,Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration,"Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Deltawhite matter binding = -23.30%, 95% confidence interval -40.9 to -5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.",microglia;minocycline;neurodegeneration;positron emission tomography;traumatic brain injury,"Scott, G.;Zetterberg, H.;Jolly, A.;Cole, J. H.;De Simoni, S.;Jenkins, P. O.;Feeney, C.;Owen, D. R.;Lingford-Hughes, A.;Howes, O.;Patel, M. C.;Goldstone, A. P.;Gunn, R. N.;Blennow, K.;Matthews, P. M.;Sharp, D. J.",2018,Feb 1,,0,
1365,Amyloid pathology and axonal injury after brain trauma,"OBJECTIVE: To image beta-amyloid (Abeta) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Abeta are correlated, and compare the spatial distribution of Abeta to Alzheimer disease (AD). METHODS: Patients 11 months to 17 years after moderate-severe TBI underwent (11)C-Pittsburgh compound B ((11)C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of (11)C-PiB, which index Abeta plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with (11)C-PiB BPND. RESULTS: Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased (11)C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum. CONCLUSIONS: Increased Abeta burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.",,"Scott, G.;Ramlackhansingh, A. F.;Edison, P.;Hellyer, P.;Cole, J.;Veronese, M.;Leech, R.;Greenwood, R. J.;Turkheimer, F. E.;Gentleman, S. M.;Heckemann, R. A.;Matthews, P. M.;Brooks, D. J.;Sharp, D. J.",2016,Mar 1,10.1212/wnl.0000000000002413,0,
1366,Aβ-related angiitis: Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy,"Idiopathic or primary angiitis of the CNS (PACNS) and cerebral amyloid angiopathy (CAA) are unusual vasculopathies generally regarded as unrelated disorders. A few case reports have, however, described granulomatous angiitis in patients with sporadic, amyloid β peptide (Aβ)-related CAA. Here we describe the clinical, neuroradiological and neuropathological features of nine patients with Aβ-related angiitis (ABRA). Combining these with the individual case reports drawn from the literature has allowed us to define ABRA as a clinical entity and to compare its features with those of PACNS. The mean age of presentation of ABRA (67 years) is higher than that of PACNS but lower than that of sporadic non-inflammatory Aβ-related CAA. Alterations in mental status (59%), headaches (35%), seizures and focal neurological deficits (24%) are common. Hallucinations are a presenting manifestation in 12 % of cases. Most patients have white matter hyperintensities on MRI but these are of similar appearance to those in PACNS. Cerebrospinal fluid usually shows modest elevation of protein and pleocytosis. Neuropathology reveals angiodestructive inflammation, often granulomatous, and meningeal lymphocytosis. Aβ is consistently present in abundance in affected blood vessels but usually scanty within the parenchyma of the cerebral cortex. However, the cortex includes numerous activated microglia, occasionally in a plaque-like distribution and containing cytoplasmic Aβ. The cerebral white matter shows patchy gliosis and rarefaction, in some cases marked. Our findings (i) help to dissect one separate clinicopathological entity from what is likely to be a spectrum of primary angiitides of the CNS; (ii) have important therapeutic implications for one category of patients with amyloid-related vasculopathy; and (iii) may provide valuable insights into the development of amyloid-associated inflammation, of relevance not only to ABRA but also to Aβ-immunization- related encephalitis and to Alzheimer's disease. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.",aciclovir;amyloid beta protein;azathioprine;cyclophosphamide;dexamethasone;heparin;immunoglobulin;prednisolone;steroid;adult;aged;Alzheimer disease;amyloid beta angiitis;article;brain angiography;brain cortex;brain vasculitis;central nervous system;cerebrospinal fluid examination;clinical article;clinical feature;computer assisted tomography;female;granulomatous inflammation;hallucination;human;human tissue;immunization;inflammation;lymphomatosis;male;mental health;microglia;neuroimaging;neuropathology;nuclear magnetic resonance imaging;onset age;primary angiitis of the central nervous system;priority journal;vascular amyloidosis,"Scolding, N. J.;Joseph, F.;Kirby, P. A.;Mazanti, I.;Gray, F.;Mikol, J.;Ellison, D.;Hilton, D. A.;Williams, T. L.;MacKenzie, J. M.;Xuereb, J. H.;Love, S.",2005,,,0,
1367,A diffusion tensor MRI study of patients with MCI and AD with a 2-year clinical follow-up,"OBJECTIVE: The authors assessed whether brain changes detected by diffusion tensor (DT) MRI can improve the understanding of structural damage in Alzheimer's disease (AD) and are associated with different risks of conversion to AD in amnestic mild cognitive impairment (aMCI). METHODS: Twenty-one aMCI patients, 21 AD patients and 20 healthy subjects underwent conventional and DT MRI at baseline. All subjects were clinically followed up over 2 years; at the end of follow-up, aMCI were grouped into converters to AD (aMCI-C) and non-converters (aMCI-NC). The mean diffusivity (MD) and fractional anisotropy (FA) were obtained from total grey matter (GM) and white matter (WM), and from several GM and WM regions of interest (ROIs). On T1-weighted images, normalised volumes of the whole brain (NBV), GM (NGMV) and WM were measured. RESULTS: A significant 'trend' of worsening with a trajectory 'normal/aMCI/AD' was found for NBV and NGMV, total GM and WM MD, total WM FA, as well as for diffusivity abnormalities in several GM and WM ROIs, mainly located in posterior brain regions. aMCI-C had GM and WM changes similar to those seen in AD, whereas aMCI-NC showed a DT MRI pattern similar to that of healthy subjects. DT MRI metrics that better distinguished aMCI-C from aMCI-NC were MD of total GM and WM, hippocampi, anterior insulae, frontal and parietal WM, occipital GM and WM, and FA of temporal WM. Volumetric variables were not able to distinguish the two aMCI subgroups (aMCI-C and aMCI-NC). CONCLUSIONS: Subtle brain diffusivity changes occur from the prodromal stages of AD, mainly in posterior brain regions, and spread over the course of the disease to involve the frontal lobe. In aMCI, the severity of microstructural damage within and beyond the medial temporal lobe is associated with an increased short-term risk to develop AD.","Aged;Alzheimer Disease/complications/ pathology/psychology;Amnesia/etiology/psychology;Brain/pathology;Diffusion Magnetic Resonance Imaging;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Infarction, Middle Cerebral Artery/complications/ pathology;Longitudinal Studies;Male;Middle Aged;Neuropsychological Tests;Software","Scola, E.;Bozzali, M.;Agosta, F.;Magnani, G.;Franceschi, M.;Sormani, M. P.;Cercignani, M.;Pagani, E.;Falautano, M.;Filippi, M.;Falini, A.",2010,Jul,10.1136/jnnp.2009.189639,0,
1368,"Small infarctions of cochlear, retinal, and encephalic tissue in young women","Background and Purpose: Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies. Case Descriptions: Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective. Conclusions: Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated.",,"Schwitter, J.;Agosti, R.;Ott, P.;Kalman, A.;Waespe, W.",1992,1992,,0,
1369,Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia,"Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes.","Aged;Anisotropy;Aphasia, Primary Progressive/ pathology/ physiopathology;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Functional Laterality;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Semantics","Schwindt, G. C.;Graham, N. L.;Rochon, E.;Tang-Wai, D. F.;Lobaugh, N. J.;Chow, T. W.;Black, S. E.",2013,Apr,10.1002/hbm.21484,0,
1370,"Optimizing PiB-PET SUVR change-over-time measurement by a large-scale analysis of longitudinal reliability, plausibility, separability, and correlation with MMSE","Quantitative measurements of change in beta-amyloid load from Positron Emission Tomography (PET) images play a critical role in clinical trials and longitudinal observational studies of Alzheimer's disease. These measurements are strongly affected by methodological differences between implementations, including choice of reference region and use of partial volume correction, but there is a lack of consensus for an optimal method. Previous works have examined some relevant variables under varying criteria, but interactions between them prevent choosing a method via combined meta-analysis. In this work, we present a thorough comparison of methods to measure change in beta-amyloid over time using Pittsburgh Compound B (PiB) PET imaging. METHODS: We compare 1,024 different automated software pipeline implementations with varying methodological choices according to four quality metrics calculated over three-timepoint longitudinal trajectories of 129 subjects: reliability (straightness/variance); plausibility (lack of negative slopes); ability to predict accumulator/non-accumulator status from baseline value; and correlation between change in beta-amyloid and change in Mini Mental State Exam (MMSE) scores. RESULTS AND CONCLUSION: From this analysis, we show that an optimal longitudinal measure of beta-amyloid from PiB should use a reference region that includes a combination of voxels in the supratentorial white matter and those in the whole cerebellum, measured using two-class partial volume correction in the voxel space of each subject's corresponding anatomical MR image.","0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole);0 (Amyloid beta-Peptides);0 (Aniline Compounds);0 (Thiazoles);Adult;Aged;Aged, 80 and over;Amyloid beta-Peptides/ metabolism;Aniline Compounds;Brain/ diagnostic imaging/ metabolism;Cognitive Dysfunction/diagnostic imaging;Dementia/diagnostic imaging;Female;Humans;Longitudinal Studies;Male;Middle Aged;Positron-Emission Tomography/ methods/standards;Reproducibility of Results;Thiazoles","Schwarz, C. G.;Senjem, M. L.;Gunter, J. L.;Tosakulwong, N.;Weigand, S. D.;Kemp, B. J.;Spychalla, A. J.;Vemuri, P.;Petersen, R. C.;Lowe, V. J.;Jack, C. R., Jr.",2017,Jan 1,,0,
1371,"Optimizing PiB-PET SUVR Change-Over-Time Measurement by a large-scale analysis of Longitudinal Reliability, Plausibility, Separability, and Correlation with MMSE","Quantitative measurements of change in beta-amyloid load from Positron Emission Tomography (PET) images play a critical role in clinical trials and longitudinal observational studies of Alzheimer's disease. These measurements are strongly affected by methodological differences between implementations, including choice of reference region and use of partial volume correction, but there is a lack of consensus for an optimal method. Previous works have examined some relevant variables under varying criteria, but interactions between them prevent choosing a method via combined meta-analysis. In this work, we present a thorough comparison of methods to measure change in beta-amyloid over time using Pittsburgh Compound B (PiB) PET imaging. METHODS: We compare 1,024 different automated software pipeline implementations with varying methodological choices according to four quality metrics calculated over three-timepoint longitudinal trajectories of 129 subjects: reliability (straightness/variance); plausibility (lack of negative slopes); ability to predict accumulator/non-accumulator status from baseline value; and correlation between change in beta-amyloid and change in Mini Mental State Exam (MMSE) scores. RESULTS AND CONCLUSION: From this analysis, we show that an optimal longitudinal measure of beta-amyloid from PiB should use a reference region that includes a combination of voxels in the supratentorial white matter and those in the whole cerebellum, measured using two-class partial volume correction in the voxel space of each subject's corresponding anatomical MR image.",,"Schwarz, C. G.;Senjem, M. L.;Gunter, J. L.;Tosakulwong, N.;Weigand, S. D.;Kemp, B. J.;Spychalla, A. J.;Vemuri, P.;Petersen, R. C.;Lowe, V. J.;Jack, C. R., Jr.",2016,Aug 27,10.1016/j.neuroimage.2016.08.056,0,1370
1372,Improved DTI registration allows voxel-based analysis that outperforms Tract-Based Spatial Statistics,"Tract-Based Spatial Statistics (TBSS) is a popular software pipeline to coregister sets of diffusion tensor Fractional Anisotropy (FA) images for performing voxel-wise comparisons. It is primarily defined by its skeleton projection step intended to reduce effects of local misregistration. A white matter ""skeleton"" is computed by morphological thinning of the inter-subject mean FA, and then all voxels are projected to the nearest location on this skeleton. Here we investigate several enhancements to the TBSS pipeline based on recent advances in registration for other modalities, principally based on groupwise registration with the ANTS-SyN algorithm. We validate these enhancements using simulation experiments with synthetically-modified images. When used with these enhancements, we discover that TBSS's skeleton projection step actually reduces algorithm accuracy, as the improved registration leaves fewer errors to warrant correction, and the effects of this projection's compromises become stronger than those of its benefits. In our experiments, our proposed pipeline without skeleton projection is more sensitive for detecting true changes and has greater specificity in resisting false positives from misregistration. We also present comparative results of the proposed and traditional methods, both with and without the skeleton projection step, on three real-life datasets: two comparing differing populations of Alzheimer's disease patients to matched controls, and one comparing progressive supranuclear palsy patients to matched controls. The proposed pipeline produces more plausible results according to each disease's pathophysiology. © 2014.",,"Schwarz, C. G.;Reid, R. I.;Gunter, J. L.;Senjem, M. L.;Przybelski, S. A.;Zuk, S. M.;Whitwell, J. L.;Vemuri, P.;Josephs, K. A.;Kantarci, K.;Thompson, P. M.;Petersen, R. C.;Jack, C. R.",2014,1,,0,
1373,Contributions of imprecision in PET-MRI rigid registration to imprecision in amyloid PET SUVR measurements,"Quantitative measurement of beta-amyloid from amyloid PET scans typically relies on localizing target and reference regions by image registration to MRI. In this work, we present a series of simulations where 50 small random perturbations of starting location and orientation were applied to each subject's PET scan, and rigid registration using spm_coreg was performed between each perturbed PET scan and its corresponding MRI. We then measured variation in the output PET-MRI registrations and how this variation affected the resulting SUVR measurements. We performed these experiments using scans of 1196 participants, half using 18F florbetapir and half using 11C PiB. From these experiments, we measured the magnitude of the imprecision in the rigid registration steps used to localize measurement regions, and how this contributes to the overall imprecision in SUVR measurements. Unexpectedly, we found for both tracers that the imprecision in these measurements depends on the degree of amyloid tracer uptake, and thus also indirectly on Alzheimer's disease clinical status. We then examined common choices of reference regions, and we show that SUVR measurements using supratentorial white matter references are relatively resistant to this source of error. We also show that the use of partial volume correction further magnifies the effects of registration imprecision on SUVR measurements. Together, these results suggest that this rigid registration step is an attractive target for future work in improving measurement techniques. Hum Brain Mapp, 2017. (c) 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.",Alzheimer disease;Pittsburgh compound B;amyloid;computer-assisted;florbetapir;image processing;positron-emission tomography;reproducibility of results,"Schwarz, C. G.;Jones, D. T.;Gunter, J. L.;Lowe, V. J.;Vemuri, P.;Senjem, M. L.;Petersen, R. C.;Knopman, D. S.;Jack, C. R., Jr.;Alzheimer's Disease Neuroimaging, Initiative",2017,Apr 22,,0,
1374,Fully-automated white matter hyperintensity detection with anatomical prior knowledge and without FLAIR,"This paper presents a method for detection of cerebral white matter hyperintensities (WMH) based on run-time PD-, T1-, and T2-weighted structural magnetic resonance (MR) images of the brain along with labeled training examples. Unlike most prior approaches, the method is able to reliably detect WMHs in elderly brains in the absence of fluid-attenuated (FLAIR) images. Its success is due to the learning of probabilistic models of WMH spatial distribution and neighborhood dependencies from ground-truth examples of FLAIR-based WMH detections. These models are combined with a probabilistic model of the PD, T1, and T2 intensities of WMHs in a Markov Random Field (MRF) framework that provides the machinery for inferring the positions of WMHs in novel test images. The method is shown to accurately detect WMHs in a set of 114 elderly subjects from an academic dementia clinic. Experiments show that standard off-the-shelf MRF training and inference methods provide robust results, and that increasing the complexity of neighborhood dependency models does not necessarily help performance. The method is also shown to perform well when training and test data are drawn from distinct scanners and subject pools.","Algorithms;Artificial Intelligence;Brain/ pathology;Demyelinating Diseases/pathology;Diffuse Axonal Injury/ pathology;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Nerve Fibers, Myelinated/ pathology;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity","Schwarz, C.;Fletcher, E.;DeCarli, C.;Carmichael, O.",2009,,,0,
1375,"Computed tomographic analysis of brain morphometrics in 30 healthy men, aged 21 to 81 years","Computed transverse axial tomography (CT) was employed to examine brain morphometrics in 30 healthy men, aged 21 to 81 years. Seven consecutive CT slices 30 to 80 mm above the inferior orbitomeatal line were analyzed. CT numbers in gray and white matter regions were not correlated significantly with age (p<0.05), nor were right/left ratios for derived parameters. The volume of gray matter was correlated negatively with age (p<0.05), and the volume of cerebrospinal fluid correlated positively with age, in the seven slices. The volumes of the lateral and third ventricles were elevated in the elderly, and volumes of the thalamus and lenticular nucleus were reduced. The results demonstrate that brain atrophy, evidenced by a loss of gray matter and by dilatation of cerebrospinal fluid spaces, occurs in the healthy elderly, and provide baseline CT-derived brain morphometric data for healthy men in relation to age.",adult;age;aged;brain;brain ventricle;central nervous system;computer analysis;computer assisted tomography;diagnosis;human;human experiment;lenticular ansa;morphometrics;normal human;priority journal;thalamus,"Schwartz, M.;Creasey, H.;Grady, C. L.",1985,,,0,
1376,Treatment of leukoaraiosis,"Altered signal intensity in the subcortical white matter on magnetic resonance imaging of the brain, referred to as leukoaraiosis, is frequently observed on imaging studies in elderly persons and was previously considered a benign accompaniment of aging. However, recent studies have found a clear association between the presence of leukoaraiosis and an increased risk for stroke, cognitive decline, and dementia. Moreover, epidemiologic studies have shown an association of leukoaraiosis with age, and several risk factors that are amenable to treatment, including smoking, hypertension, diabetes, homocysteinemia, hyperlipidemia, and excess alcohol use. Although results from prospective trials are not available, current evidence suggests that vigorous treatment of cardiovascular disease risk factors may prevent the development or progression of leukoaraiosis and the attendant risks of stroke and dementia.",,"Schwartz, G. L.;Fornage, M.;Mosley, T.;Turner, S. T.",2005,Jul,,0,
1377,Association of ambulatory blood pressure with ischemic brain injury,"Cerebral white matter hyperintensities on brain MRI (leukoaraiosis) are associated with increased risk of stroke and dementia. To assess the relationships of blood pressure level and circadian pattern with leukoaraiosis, we obtained 24-hour ambulatory blood pressure recordings and brain magnetic resonance images in 343 white and 267 black adults who were members of sibships that had >or=2 siblings with essential hypertension. In multiple linear regression models, factors associated with greater leukoaraiosis in both racial groups included age (P<or=0.002), homocysteine levels (P<or=0.006), and brain volume (P<or=0.008). In blacks, ambulatory blood pressure measures associated with greater leukoaraiosis were higher awake, asleep, and 24-hour systolic and diastolic levels (P<or=0.009 for each). In addition, there was a trend for smaller nocturnal declines in systolic and diastolic levels (ie, nondipping patterns) to be associated with greater leukoaraiosis, and all of these associations, except nondipping of diastolic level, remained or became significant after controlling for office blood pressure (P<0.05 for each). In whites, among ambulatory blood pressure measures, only higher asleep diastolic levels trended toward association with greater leukoaraiosis. However, similar to findings in blacks, nondipping of systolic and diastolic ambulatory blood pressure levels were each associated with greater leukoaraiosis (P<or=0.008), and all of these associations remained or became significant after controlling for office blood pressure (P<or=0.009 for each). Higher ambulatory blood pressure levels and a nondipping circadian pattern contribute to greater leukoaraiosis volume after controlling for office blood pressure.","African Continental Ancestry Group;Aged;Blood Pressure/ physiology;Blood Pressure Monitoring, Ambulatory;Brain Ischemia/ etiology/pathology/ physiopathology;Circadian Rhythm/ physiology;Cross-Sectional Studies;European Continental Ancestry Group;Female;Homocysteine/blood;Humans;Leukoaraiosis/etiology/pathology/ physiopathology;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Sleep/physiology","Schwartz, G. L.;Bailey, K. R.;Mosley, T.;Knopman, D. S.;Jack, C. R., Jr.;Canzanello, V. J.;Turner, S. T.",2007,Jun,10.1161/hypertensionaha.106.078691,0,
1378,Evaluation of older persons with mild cognitive deficits: potential utility of magnetic resonance imaging,"BACKGROUND: This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits. METHODS: Fifteen participants were evaluated (mean age = 71.8 +/- 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures. RESULTS: Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS). CONCLUSIONS: Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.","Aged;Alzheimer Disease/diagnosis;Atrophy;Brain/ pathology;Cognition Disorders/ diagnosis;Diagnosis, Differential;Disability Evaluation;Dominance, Cerebral/physiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory Disorders/ diagnosis;Mental Status Schedule;Neuropsychological Tests;Organ Size/physiology;Temporal Lobe/pathology","Schultz, S. K.;Magnotta, V.;Duff, K.;Boles Ponto, L. L.;Moser, D. J.",2008,Oct-Dec,10.1080/10401230802437530,0,
1379,"Accelerated aging, decreased white matter integrity, and associated neuropsychological dysfunction 25 years after pediatric lymphoid malignancies","PURPOSE: CNS-directed chemotherapy (CT) and cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia or lymphoma have various neurotoxic properties. This study aimed to assess their impact on the maturing brain 20 to 30 years after diagnosis, providing a much stronger perspective on long-term quality of life than previous studies. PATIENTS AND METHODS: Ninety-three patients treated between 1978 and 1990 at various intensities, with and without CRT, and 49 healthy controls were assessed with magnetic resonance diffusion tensor imaging (DTI) and neuropsychological tests. Differences in fractional anisotropy (FA)-a DTI measure describing white matter (WM) microstructure-were analyzed by using whole brain voxel-based analysis. RESULTS: CRT-treated survivors demonstrated significantly decreased FA compared with controls in frontal, parietal, and temporal WM tracts. Trends for lower FA were seen in the CT-treated survivors. Decreases in FA correlated well with neuropsychological dysfunction. In contrast to the CT group and controls, the CRT group showed a steep decline of FA with age at assessment. Younger age at cranial irradiation and higher dosage were associated with worse outcome of WM integrity. CONCLUSION: CRT-treated survivors show decreased WM integrity reflected by significantly decreased FA and associated neuropsychological dysfunction 25 years after treatment, although effects of CT alone seem mild. Accelerated aging of the brain and increased risk of early onset dementia are suspected after CRT, but not after CT.","Adolescent;Adult;Brain/drug effects/ pathology/radiation effects;Case-Control Studies;Chemoradiotherapy/adverse effects;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Lymphoma/drug therapy/ pathology/radiotherapy;Male;Nerve Fibers, Myelinated/drug effects/ pathology/radiation effects;Neuropsychological Tests;Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug;therapy/ pathology/radiotherapy;Survivors;Young Adult","Schuitema, I.;Deprez, S.;Van Hecke, W.;Daams, M.;Uyttebroeck, A.;Sunaert, S.;Barkhof, F.;van Dulmen-den Broeder, E.;van der Pal, H. J.;van den Bos, C.;Veerman, A. J.;de Sonneville, L. M.",2013,Sep 20,10.1200/jco.2012.46.7050,0,
1380,"Cerebral blood flow in ischemic vascular dementia and Alzheimer's disease, measured by arterial spin-labeling magnetic resonance imaging","BACKGROUND: Our objectives were to compare the effects of subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD) on cerebral blood flow (CBF), and then to analyze the relationship between CBF and subcortical vascular disease, measured as volume of white-matter lesions (WMLs). METHODS: Eight mildly demented patients with SIVD (mean +/- SD; aged 77 +/- 8 years; Mini-Mental State Examination score 26 +/- 3 years) and 14 patients with AD were compared with 18 cognitively normal elderly subjects. All subjects had CBF measured using arterial spin-labeling magnetic resonance imaging, and brain volumes were assessed using structural magnetic resonance imaging. RESULTS: AD and SIVD showed marked CBF reductions in the frontal (P = 0.001) and parietal (P = 0.001) cortices. In SIVD, increased subcortical WMLs were associated with reduced CBF in the frontal cortex (P = 0.04), in addition to cortical atrophy (frontal, P = 0.05; parietal, P = 0.03). CONCLUSIONS: Subcortical vascular disease is associated with reduced CBF in the cortex, irrespective of brain atrophy.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/ physiopathology;Atrophy/etiology/pathology/physiopathology;Brain/blood supply/pathology/physiopathology;Brain Ischemia/pathology/ physiopathology;Brain Mapping/methods;Cerebral Arteries/ physiopathology;Cerebrovascular Circulation/ physiology;Dementia, Vascular/pathology/ physiopathology;Disease Progression;Female;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests;Sensitivity and Specificity;Severity of Illness Index;Spin Labels","Schuff, N.;Matsumoto, S.;Kmiecik, J.;Studholme, C.;Du, A.;Ezekiel, F.;Miller, B. L.;Kramer, J. H.;Jagust, W. J.;Chui, H. C.;Weiner, M. W.",2009,Nov,10.1016/j.jalz.2009.04.1233,0,
1381,Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD,"BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/pathology;Analysis of Variance;Aspartic Acid/ analogs & derivatives/ metabolism;Atrophy;Female;Humans;Magnetic Resonance Spectroscopy/methods/statistics & numerical data;Male;Middle Aged;Parietal Lobe/ metabolism/pathology;Temporal Lobe/ metabolism/pathology","Schuff, N.;Capizzano, A. A.;Du, A. T.;Amend, D. L.;O'Neill, J.;Norman, D.;Kramer, J.;Jagust, W.;Miller, B.;Wolkowitz, O. M.;Yaffe, K.;Weiner, M. W.",2002,Mar 26,,0,
1382,Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD,"OBJECTIVES: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD). METHODS: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes. RESULTS: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%. CONCLUSIONS: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.","Aged;Alzheimer Disease/ diagnosis/ metabolism;Aspartic Acid/ analogs & derivatives/analysis/ metabolism;Brain/metabolism/pathology;Dementia, Vascular/ diagnosis/ metabolism;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Neuropsychological Tests;Predictive Value of Tests;Reference Values","Schuff, N.;Capizzano, A. A.;Du, A. T.;Amend, D. L.;O'Neill, J.;Norman, D.;Jagust, W. J.;Chui, H. C.;Kramer, J. H.;Reed, B. R.;Miller, B. L.;Yaffe, K.;Weiner, M. W.",2003,Aug 12,,0,
1383,Neurovascular coupling is impaired in cerebral microangiopathy--An event-related Stroop study,"Small-vessel disease or cerebral microangiopathy is a common finding in elderly people leading finally to subcortical ischemic vascular dementia. Because cerebral microangiopathy impairs vascular reactivity and affects mainly the frontal lobes, we hypothesized that brain activation decreases during an event-related color-word matching Stroop task. 12 patients suffering from cerebral microangiopathy were compared with 12 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. The Stroop task led to activations in the lateral prefrontal cortex. Generally, the amplitude of the hemodynamic response was reduced in patients in tight correlation with behavioral slowing during the Stroop task and with neuropsychological deficits, namely attentional and executive dysfunction. Interestingly, patients showed an early deoxygenation of blood right after stimulation onset, and a delay of the hemodynamic response. Whereas the amplitude of the hemodynamic response is reduced in the frontal lobes also with normal aging, data suggest that impairments of neurovascular coupling are specific for cerebral microangiopathy. In summary, our findings indicate frontal dysfunction and impairments of neurovascular coupling in cerebral microangiopathy.","Aged;Behavior;Cerebral Arterial Diseases/ physiopathology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Spectroscopy, Near-Infrared","Schroeter, M. L.;Cutini, S.;Wahl, M. M.;Scheid, R.;Yves von Cramon, D.",2007,Jan 1,10.1016/j.neuroimage.2006.09.001,0,
1384,Spontaneous slow hemodynamic oscillations are impaired in cerebral microangiopathy,"Small-vessel disease or cerebral microangiopathy (CMA) is a common finding in elderly people. It is related to a variety of vascular risk factors and may finally lead to subcortical ischemic vascular dementia. Because vessel stiffness is increased, we hypothesized that slow spontaneous oscillations are reduced in cerebral hemodynamics. Accordingly, we examined spontaneous oscillations in the visual cortex of 13 patients suffering from CMA, and compared them with 14 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. Spontaneous low-frequency oscillations (LFOs) (0.07 to 0.12 Hz) were specifically impaired in CMA in contrast to spontaneous very-low-frequency oscillations (0.01 to 0.05 Hz), which remained unaltered. Vascular reagibility was reduced during visual stimulation. Interestingly, changes were tightly related to neuropsychological deficits, namely executive dysfunction. Vascular alterations had to be attributed mainly to the vascular risk factor arterial hypertension. Further, results suggest that the impairments might be, at least partly, reversed by medical treatment such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Results indicate that functional near-infrared spectroscopy may detect changes in the microvasculature due to CMA, namely an impairment of spontaneous LFOs, and of vascular reagibility. Hence, CMA accelerates microvascular changes due to aging, leading to impairments of autoregulation.","Aged;Brain Ischemia/pathology/ physiopathology;Cerebral Angiography;Cerebrovascular Circulation;Dementia, Vascular/pathology/ physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Microcirculation;Middle Aged;Neuropsychological Tests;Periodicity;Spectroscopy, Near-Infrared","Schroeter, M. L.;Bucheler, M. M.;Preul, C.;Scheid, R.;Schmiedel, O.;Guthke, T.;von Cramon, D. Y.",2005,Dec,10.1038/sj.jcbfm.9600159,0,
1385,Computerized tomography (CT) in multi-infarct (MID) and dementia of Alzheimer's type (DAT),,Alzheimer disease;computer analysis;computer assisted tomography;dementia;electroencephalography;human;major clinical study;multiinfarct dementia;psychological aspect,"Schroder, J.;Haan, J.;Dickmann, E.",1989,,,0,
1386,Is dementia incidence declining?: Trends in dementia incidence since 1990 in the Rotterdam Study,"OBJECTIVE: To investigate whether dementia incidence has changed over the last 2 decades. METHODS: We compared dementia incidence in 2 independent subcohorts of persons aged 60-90 years from the Rotterdam Study, a population-based cohort study. The first subcohort started in 1990 (n = 5,727), the second in 2000 (n = 1,769). Participants were dementia-free at baseline and followed for at maximum 5 years. We calculated age-adjusted dementia incidence rates for the 2 subcohorts in total, in 10-year age strata, and for men and women separately. We also compared mortality rates, differences in prevalence of vascular risk factors, and medication use. Finally, we compared brain volumes and the extent of cerebral small vessel disease in participants who underwent brain imaging 5 years after the baseline examinations. RESULTS: In the 1990 subcohort (25,696 person-years), 286 persons developed dementia, and in the 2000 subcohort (8,384 person-years), 49 persons. Age-adjusted dementia incidence rates were consistently, yet nonsignificantly, lower in the 2000 subcohort in all strata, reaching borderline significance in the overall analysis (incidence rate ratio 0.75, 95% confidence interval [CI] 0.56-1.02). Mortality rates were also lower in the 2000 subcohort (rate ratio 0.63, 95% CI 0.52-0.77). The prevalence of hypertension and obesity significantly increased between 1990 and 2000. This was paralleled by a strong increase in use of antithrombotics and lipid-lowering drugs. Participants in 2005-2006 had larger total brain volumes (p < 0.001) and less cerebral small vessel disease (although nonsignificant in men) than participants in 1995-1996. CONCLUSIONS: Although the differences in dementia incidence were nonsignificant, our study suggests that dementia incidence has decreased between 1990 and 2005.","Age Distribution;Aged;Aged, 80 and over;Dementia/ epidemiology;Female;Humans;Incidence;Male;Middle Aged;Prevalence;Sex Distribution","Schrijvers, E. M.;Verhaaren, B. F.;Koudstaal, P. J.;Hofman, A.;Ikram, M. A.;Breteler, M. M.",2012,May 8,10.1212/WNL.0b013e3182553be6,0,
1387,Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla,"Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 +/- 5.7 years, Mini-Mental State Examination 29.4 +/- 4.1). The Verbal Learning and Memory Test (VLMT) was administered as part of a neuropsychological battery for assessment of episodic memory performance. Significant differences between PCP gray and white matter could be observed for glutamate-glutamine (p = 0.001), choline (p = 0.01), and myo-inositol (p = 0.02). Low Verbal Learning and Memory Test performance was associated with high N-acetylaspartate in PCP gray matter (p = 0.01) but not in PCP white matter. Our data suggest that subtle decreases in episodic memory performance in the elderly may be associated with increased levels of N-acetylaspartate as a reflection of increased mitochondrial energy capacity in PCP gray matter.",7 Tesla;Aging;Episodic memory;Human subjects;Magnetic resonance spectroscopic imaging;Posterior cingulate,"Schreiner, S. J.;Kirchner, T.;Wyss, M.;Van Bergen, J. M.;Quevenco, F. C.;Steininger, S. C.;Griffith, E. Y.;Meier, I.;Michels, L.;Gietl, A. F.;Leh, S. E.;Brickman, A. M.;Hock, C.;Nitsch, R. M.;Pruessmann, K. P.;Henning, A.;Unschuld, P. G.",2016,Dec,,0,
1388,Brain amyloid burden and cerebrovascular disease are synergistically associated with neurometabolism in cognitively unimpaired older adults,"Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Abeta) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown. Thirty cognitively normal older adults (age = 70 +/- 5.6 years, Mini-Mental State Examination = 29.2 +/- 1) received 11-C-Pittsburgh Compound B positron emission tomography for estimating Abeta-plaque density, 7 Tesla fluid-attenuated inversion recovery magnetic resonance imaging for quantifying white matter hyperintensity volume as a marker of small vessel cerebrovascular disease and high-resolution magnetic resonance spectroscopic imaging at 7 Tesla, based on free induction decay acquisition localized by outer volume suppression to investigate tissue-specific neurometabolism in the posterior cingulate and precuneus. Abeta (beta = 0.45, p = 0.018) and white matter hyperintensities (beta = 0.40, p = 0.046) were independently and interactively (beta = -0.49, p = 0.026) associated with a higher ratio of mI over NAA (mI/NAA) in the posterior cingulate and precuneus gray matter but not in the white matter. Our data suggest that cerebrovascular disease and Abeta burden are synergistically associated with AD-related gray matter neurometabolism in older adults.",7 Tesla;Alzheimer's disease;Beta amyloid;Magnetic resonance spectroscopic imaging;Pet;White matter hyperintensities,"Schreiner, S. J.;Kirchner, T.;Narkhede, A.;Wyss, M.;Van Bergen, J. M. G.;Steininger, S. C.;Gietl, A.;Leh, S. E.;Treyer, V.;Buck, A.;Pruessmann, K. P.;Nitsch, R. M.;Hock, C.;Henning, A.;Brickman, A. M.;Unschuld, P. G.",2018,Mar,,0,
1389,Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model,"Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts.We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP.In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians.",,"Schreiber, S.;Bueche, C. Z.;Garz, C.;Braun, H.",2013,,10.1186/2040-7378-5-4,0,
1390,Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study,"Neuroimaging with iron-sensitive MR sequences [gradient echo T2* and susceptibility-weighted imaging (SWI)] identifies small signal voids that are suspected brain microbleeds. Though the clinical significance of these lesions remains uncertain, their distribution and prevalence correlates with cerebral amyloid angiopathy (CAA), hypertension, smoking, and cognitive deficits. Investigation of the pathologies that produce signal voids is necessary to properly interpret these imaging findings. We conducted a systematic correlation of SWI-identified hypointensities to tissue pathology in postmortem brains with Alzheimer's disease (AD) and varying degrees of CAA. Autopsied brains from eight AD patients, six of which showed advanced CAA, were imaged at 3T; foci corresponding to hypointensities were identified and studied histologically. A variety of lesions was detected; the most common lesions were acute microhemorrhage, hemosiderin residua of old hemorrhages, and small lacunes ringed by hemosiderin. In lesions where the bleeding vessel could be identified, beta-amyloid immunohistochemistry confirmed the presence of beta-amyloid in the vessel wall. Significant cellular apoptosis was noted in the perifocal region of recent bleeds along with heme oxygenase 1 activity and late complement activation. Acutely extravasated blood and hemosiderin were noted to migrate through enlarged Virchow-Robin spaces propagating an inflammatory reaction along the local microvasculature; a mechanism that may contribute to the formation of lacunar infarcts. Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease.","Aged;Alzheimer Disease/pathology;Blood Vessels/pathology;Brain Ischemia/etiology/pathology;Cerebral Amyloid Angiopathy/metabolism/ pathology;Coloring Agents;Complement C6/metabolism;Dementia/ pathology;Disease Progression;Dissection;Female;Fluorescent Dyes;Hemosiderin/metabolism;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Inflammation/pathology;Intracranial Hemorrhages/pathology;Magnetic Resonance Imaging;Male;Nerve Tissue Proteins/metabolism","Schrag, M.;McAuley, G.;Pomakian, J.;Jiffry, A.;Tung, S.;Mueller, C.;Vinters, H. V.;Haacke, E. M.;Holshouser, B.;Kido, D.;Kirsch, W. M.",2010,Mar,10.1007/s00401-009-0615-z,0,
1391,"Effect of cerebral amyloid angiopathy on brain iron, copper, and zinc in Alzheimer's disease","Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI-detectable microbleeds in many of these patients. It is possible that CAA-related microbleeding is a source of pathological iron in the AD brain. Because the homeostasis of copper, iron, and zinc are so intimately linked, we determined whether CAA contributes to changes in the brain levels of these metals. We obtained brain tissue from AD patients with severe CAA to compare to AD patients without evidence of vascular amyloid-beta. Patients with severe CAA had significantly higher non-heme iron levels. Histologically, iron was deposited in the walls of large CAA-affected vessels. Zinc levels were significantly elevated in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD tissues and copper was found to be prominently deposited on the vasculature in CAA. Together, these findings demonstrate that CAA is a significant variable affecting transition metals in AD.","Aged;Aged, 80 and over;Alzheimer Disease/*metabolism/pathology;Biomarkers/metabolism;Brain/*metabolism/pathology;Cerebral Amyloid Angiopathy/*metabolism/pathology;Copper/*metabolism;Female;Humans;Iron/*metabolism;Male;Middle Aged;Zinc/*metabolism","Schrag, M.;Crofton, A.;Zabel, M.;Jiffry, A.;Kirsch, D.;Dickson, A.;Mao, X. W.;Vinters, H. V.;Domaille, D. W.;Chang, C. J.;Kirsch, W.",2011,,10.3233/jad-2010-101503,0,
1392,Anatomical connection strength predicts dopaminergic drug effects on fronto-striatal function,"OBJECTIVES: We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal functioning are associated with individual differences in white matter tracts.METHODS: The effects of the dopamine receptor agonist bromocriptine were assessed using functional magnetic resonance imaging in 22 healthy volunteers in a placebo-controlled, double-blind, within-subject design. Human psychopharmacology and functional neuroimaging were combined with functional connectivity analyses and structural connectivity analyses to establish a link between dopaminergic drug effects on fronto-striatal function and fronto-striatal anatomy.RESULTS: We demonstrate that bromocriptine alters functional signals associated with attention switching in the basal ganglia. Crucially, individual differences in the drug's effect on these signals could be predicted from individual differences in fronto-striato-thalamic white matter tracts, as indexed by diffusion tensor imaging. Anatomical fronto-striatal connectivity also predicted drug effects on switch-related functional connectivity between the basal ganglia and the prefrontal cortex.CONCLUSIONS: These data reinforce the link between dopamine, cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto-striatal connection strength.RATIONALE: The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto-striatal circuitry and has been implicated in many neuropsychiatric disorders. However, there is a large variability in the direction and extent of dopaminergic drug effects across individuals.","Attention [drug effects];Brain Mapping;Bromocriptine [pharmacokinetics] [pharmacology];Corpus Striatum [anatomy & histology] [drug effects] [metabolism];Diffusion Tensor Imaging;Dopamine Agonists [pharmacokinetics] [pharmacology];Double-Blind Method;Neuropsychological Tests;Receptors, Dopamine [metabolism];Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Young Adult[checkword]","Schouwenburg, M. R.;Zwiers, M. P.;Schaaf, M. E.;Geurts, D. E.;Schellekens, A. F.;Buitelaar, J. K.;Verkes, R. J.;Cools, R.",2014,,,0,
1393,Individual classification of Alzheimer's disease with diffusion magnetic resonance imaging,"Diffusion magnetic resonance imaging (MRI) is a powerful non-invasive method to study white matter integrity, and is sensitive to detect differences in Alzheimer's disease (AD) patients. Diffusion MRI may be able to contribute towards reliable diagnosis of AD. We used diffusion MRI to classify AD patients (N=77), and controls (N=173). We use different methods to extract information from the diffusion MRI data. First, we use the voxel-wise diffusion tensor measures that have been skeletonised using tract based spatial statistics. Second, we clustered the voxel-wise diffusion measures with independent component analysis (ICA), and extracted the mixing weights. Third, we determined structural connectivity between Harvard Oxford atlas regions with probabilistic tractography, as well as graph measures based on these structural connectivity graphs. Classification performance for voxel-wise measures ranged between an AUC of 0.888, and 0.902. The ICA-clustered measures ranged between an AUC of 0.893, and 0.920. The AUC for the structural connectivity graph was 0.900, while graph measures based upon this graph ranged between an AUC of 0.531, and 0.840. All measures combined with a sparse group lasso resulted in an AUC of 0.896. Overall, fractional anisotropy clustered into ICA components was the best performing measure. These findings may be useful for future incorporation of diffusion MRI into protocols for AD classification, or as a starting point for early detection of AD using diffusion MRI.",Alzheimer's disease;Classification;Dti;Diffusion;Mri,"Schouten, T. M.;Koini, M.;Vos, F.;Seiler, S.;Rooij, M.;Lechner, A.;Schmidt, R.;Heuvel, M. V.;Grond, J. V.;Rombouts, S. A.",2017,Mar 16,,0,
1394,"Combining anatomical, diffusion, and resting state functional magnetic resonance imaging for individual classification of mild and moderate Alzheimer's disease","Magnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N = 77) from the prospective registry on dementia study and controls (N = 173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.",,"Schouten, T. M.;Koini, M.;de Vos, F.;Seiler, S.;van der Grond, J.;Lechner, A.;Hafkemeijer, A.;Moller, C.;Schmidt, R.;de Rooij, M.;Rombouts, S. A.",2016,,10.1016/j.nicl.2016.01.002,0,
1395,Development of selective verbal memory impairment secondary to a left thalamic infarct: A longitudinal case study,"A 68 year old man suffered an acute dysphasic episode with persistent memory disturbance while taking part as a control in a longitudinal magnetic resonance imaging (MRI) study. A small new left thalamic infarct involving the mamillo-thalamic tract could be demonstrated on volumetric MRI, coinciding with the development of a selective verbal memory impairment. This suggests that lateralisation of cognitive processing of visual and verbal material exists at the thalamic as well as the cortical level. High resolution volumetric MRI may be helpful in demonstrating small subcortical infarcts that may not be seen using computed tomography or conventional MRI.",,"Schott, J. M.;Crutch, S. J.;Fox, N. C.;Warrington, E. K.",2003,1,,0,
1396,"""CADASIL coma"": an underdiagnosed acute encephalopathy","The main clinical features of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) are stroke, dementia, and migraine. A reversible acute encephalopathy was the principal presentation in six of 70 patients in a British prevalence study. The episodes lasted seven to 14 days, presenting with fever, acute confusion, coma, and fits; there was full recovery but in two cases identical episodes recurred some years later. All patients had a previous history of migraine with aura and were originally misdiagnosed as viral encephalitis. CADASIL should be considered in acute unexplained encephalopathies. MRI white matter changes, previous migraine with aura, and a family history of stroke and dementia may be useful pointers to the diagnosis.","Acute Disease;Adult;Brain/pathology;Chromosome Aberrations;Coma/*etiology/genetics;Dementia, Multi-Infarct/*diagnosis/genetics;Diagnosis, Differential;Electroencephalography;Female;Follow-Up Studies;Genes, Dominant/genetics;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Migraine with Aura/diagnosis/genetics;Neurologic Examination","Schon, F.;Martin, R. J.;Prevett, M.;Clough, C.;Enevoldson, T. P.;Markus, H. S.",2003,Feb,,0,
1397,Pathophysiology and Treatment of Neurodegeneration with Brain Iron Accumulation in the Pediatric Population,"Opinion statement: Syndromes of neurodegeneration with brain iron accumulation (NBIA) are characterized by increased iron deposition in the basal ganglia leading to complex progressive neurological symptoms. Several genetically distinct subforms have been recognized. In addition to pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), further genetic causes continue to be identified. Most of these present in childhood and are inherited following an autosomal recessive trait. However, the clinical and pathological spectrum has broadened and new age-dependent presentations have been described and there is overlap between the different NBIA disorders and with other diseases (such as spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis). Thus, additional clinical information (e.g., radiological findings such as precise patters of deposition of iron or co-occurrence of white matter lesions) may be useful when prioritizing genetic screening. Neuropathological work-up demonstrated variable involvement of iron deposition, but also Lewy bodies, neurofibrillary tangles and spheroid bodies. Treatment remains symptomatic. Here we review characteristic features of NBIA syndromes with a focus on pediatric cases. © 2013 Springer Science+Business Media New York.",baclofen;cholinergic receptor blocking agent;deferiprone;dopamine receptor stimulating agent;iron;pantothenate kinase;tetrabenazine;abdominal discomfort;adulthood;agranulocytosis;arthritis;article;ATP13a2 gene;autosomal recessive inheritance;basal ganglion;beta propeller associated neurodegeneration;Burke Fahn Marsden Dystonia Rating Scale;child;childhood;clinical feature;CP gene;diagnostic test;differential diagnosis;disease classification;drug half life;erosive arthritis;FA2H gene;FTL gene;gene;gene mutation;genetic screening;human;Kufor Rakeb disease;leukodystrophy;medical information;mitochondrial membrane protein associated neurodegeneration;NBIA syndrome;neurodegeneration with brain iron accumulation;neuroimaging;neurologic disease;neuronal ceroid lipofuscinosis;neutropenia;nuclear magnetic resonance imaging;onset age;PANK2 gene;pathophysiology;PLA2G6 gene;radiodiagnosis;rating scale;spastic paraplegia;symptom;WDR45 gene;white matter,"Schneider, S. A.;Zorzi, G.;Nardocci, N.",2013,,,0,
1398,The apolipoprotein E epsilon4 allele increases the odds of chronic cerebral infarction corrected detected at autopsy in older persons,"BACKGROUND AND PURPOSE: Studies investigating the relation of the apolipoprotein E (apoE) epsilon4 allele to clinical stroke and to vascular changes on magnetic resonance imaging have been conflicting. Little data are available regarding the relation of apoE epsilon4 to cerebral infarctions documented on postmortem examination. METHODS: We studied the apoE epsilon4 allele in 214 deceased members of the Religious Orders Study, a longitudinal clinical-pathologic study of aging and Alzheimer disease. The apoE genotype was determined using DNA from lymphocytes. Brains were removed a median of 5 hours (interquartile range, 5.5) after death. At postmortem examination, age, location, and size of macroscopic chronic cerebral infarctions were recorded from 1-cm coronal slabs after paraformaldehyde fixation. We also examined 20-microm paraffin-embedded sections of midfrontal and calcarine cortex for amyloid angiopathy on a scale of 1 to 4. RESULTS: Subjects included 96 males and 118 females with a mean age at death of 86 years (SD, 7). Sixty-five subjects (30.4%) had at least 1 apoE epsilon4 allele and 76 (35.5%) exhibited cerebral infarctions. More than 74% of the subjects exhibited amyloid angiopathy with a mean score of 1.4+/-1.2. After controlling for age and sex, apoE epsilon4 increased the odds of cerebral infarction by 2.3-fold (95% CI, 1.2 to 4.2). apoE epsilon4 increased the odds of cortical 3.2-fold (95% CI, 1.3 to 7.7) and subcortical infarctions 2.3-fold (95% CI, 1.2 to 4.5). The effect was unchanged after accounting for amyloid angiopathy. CONCLUSIONS: apoE epsilon4 increases the odds of chronic cerebral infarction detected at autopsy in older persons.",Aged;Alleles;Alzheimer Disease/genetics/pathology;Apolipoprotein E4;Apolipoproteins E/ genetics;Cerebral Amyloid Angiopathy/genetics/pathology;Cerebral Infarction/classification/ genetics/pathology;Chronic Disease;Female;Genetic Predisposition to Disease;Humans;Male;Vascular Diseases/genetics,"Schneider, J. A.;Bienias, J. L.;Wilson, R. S.;Berry-Kravis, E.;Evans, D. A.;Bennett, D. A.",2005,May,10.1161/01.STR.0000160747.27470.2a,0,
1399,"Diabetes, Prediabetes, and Brain Volumes and Subclinical Cerebrovascular Disease on MRI: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)","OBJECTIVE: To examine the associations of prediabetes, diabetes, and diabetes severity (as assessed by HbA1c and diabetes duration) with brain volumes and vascular pathology on brain MRI and to assess whether the associations of diabetes with brain volumes are mediated by brain vascular pathology. RESEARCH DESIGN AND METHODS: Cross-sectional study of 1,713 participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) (mean age 75 years, 60% female, 27% black, 30% prediabetes, and 35% diabetes) who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by diabetes-HbA1c status as without diabetes (<5.7% [reference]), with prediabetes (5.7 to <6.5%), and with diabetes ([defined as prior diagnosis or HbA1c >/=6.5%] <7.0% vs. >/=7.0%), with further stratification by diabetes duration (<10 vs. >/=10 years). RESULTS: In adjusted analyses, compared with participants without diabetes and HbA1c <5.7%, participants with prediabetes and those with diabetes and HbA1c <7.0% did not have significantly different brain volumes or vascular pathology (all P > 0.05), but those with diabetes and HbA1c >/=7.0% had smaller total brain volume (beta -0.20 SDs, 95% CI -0.31, -0.09), smaller regional brain volumes (including frontal, temporal, occipital, and parietal lobes; deep gray matter; Alzheimer disease signature region; and hippocampus [all P < 0.05]), and increased burden of white matter hyperintensities (WMH) (P = 0.016). Among participants with diabetes, those with HbA1c >/=7.0% had smaller total and regional brain volumes and an increased burden of WMH (all P < 0.05) compared with those with HbA1c <7.0%. Similarly, participants with longer duration of diabetes (>/=10 years) had smaller brain volumes and higher burden of lacunes (all P < 0.05) than those with a diabetes duration <10 years. We found no evidence for mediation by WMH in associations of diabetes with smaller brain volumes by structural equation models (all P > 0.05). CONCLUSIONS: More-severe diabetes (defined by higher HbA1c and longer disease duration) but not prediabetes or less-severe diabetes was associated with smaller brain volumes and an increased burden of brain vascular pathology. No evidence was found that associations of diabetes with smaller brain volumes are mediated by brain vascular pathology, suggesting that other mechanisms may be responsible for these associations.",,"Schneider, A. L. C.;Selvin, E.;Sharrett, A. R.;Griswold, M.;Coresh, J.;Jack, C. R., Jr.;Knopman, D.;Mosley, T.;Gottesman, R. F.",2017,Nov,,0,
1400,White matter brain lesions in midlife familial hypercholesterolemic patients at 3-Tesla magnetic resonance imaging,"BACKGROUND: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. PURPOSE: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. MATERIAL AND METHODS: Non-diabetic, nonsmoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. RESULTS: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+/-1.1 vs. 5.1+/-0.9 mmol/l, P<0.02 and 4.1+/-0.9 vs. 3.1+/-0.8 mmol/l, P<0.004, respectively). CONCLUSION: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI.",cholesterol;contrast medium;diagnostic agent;gadolinium pentetate;hydroxymethylglutaryl coenzyme A reductase inhibitor;adult;age;article;blood;body mass;brain;brain disease;comparative study;disease course;female;human;familial hypercholesterolemia;image enhancement;devices;magnetism;male;methodology;middle aged;nuclear magnetic resonance imaging;observer variation;pathology;risk assessment;risk factor,"Schmitz, S. A.;O'Regan, D. P.;Fitzpatrick, J.;Neuwirth, C.;Potter, E.;Tosi, I.;Hajnal, J. V.;Naoumova, R. P.",2008,,10.1080/02841850701736263,0,1401
1401,White matter brain lesions in midlife familial hypercholesterolemic patients at 3-Tesla magnetic resonance imaging,"BACKGROUND: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. PURPOSE: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. MATERIAL AND METHODS: Non-diabetic, nonsmoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. RESULTS: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+/-1.1 vs. 5.1+/-0.9 mmol/l, P<0.02 and 4.1+/-0.9 vs. 3.1+/-0.8 mmol/l, P<0.004, respectively). CONCLUSION: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI.",,"Schmitz, S. A.;O'Regan, D. P.;Fitzpatrick, J.;Neuwirth, C.;Potter, E.;Tosi, I.;Hajnal, J. V.;Naoumova, R. P.",1987,Mar,,0,
1402,White matter lesion progression: A surrogate endpoint for trials in cerebral small-vessel disease,"There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm 3 after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.",adult;aged;article;brain ischemia;cerebrovascular disease;cognitive defect;community care;controlled study;dementia;disease course;disease marker;follow up;human;major clinical study;microangiopathy;neuropathology;nuclear magnetic resonance imaging;outcomes research;priority journal;white matter;white matter lesion,"Schmidt, R.;Scheltens, Ph;Erkinjuntti, T.;Pantoni, L.;Markus, H. S.;Wallin, A.;Barkhof, F.;Fazekas, F.",2004,,,0,
1403,Cognitive impairment after acute supratentorial stroke: a 6-month follow-up clinical and computed tomographic study,"To document the occurrence, time course, and predictors of global cognitive impairment following a supratentorial stroke, we prospectively studied 41 consecutive patients with acute cerebral ischemia and no evidence of pre-existing intellectual disturbances. The Graded Neurologic Scale and Mattis Dementia Rating Scale were used to assess neurologic and cognitive deficits within the first week, 3 weeks and 6 months after the onset of symptoms. CT was performed at each examination and semiquantitative measurements of infarct volumes and brain atrophy were obtained. Sixty-one percent of patients were found to be cognitively impaired within the first week. After 6 months this deficit had resolved in 24%, but was still present in 37% of individuals. Initial findings associated with a high risk of long-term intellectual dysfunction were: 1. moderately severe cognitive impairment, 2. diminished alertness in the acute stroke stage, 3. infarction involving the temporal lobe, 4. evidence of multiple brain infarcts and 5. pronounced ventricular enlargement. Logistic regression analysis revealed temporal infarcts and evidence of multiple ischemic lesions as the most powerful predictors of persistent cognitive impairment. By these two factors alone, 85.4% of study participants could be correctly classified regarding their cognitive outcome. These results suggest cognitive dysfunction to be a frequent sequela of supratentorial stroke. Its long-term persistence may be predicted on the basis of certain features.","Adult;Aged;Atrophy/radiography;Brain/pathology/radiography;Cerebral Infarction/diagnosis/radiography;Cerebrovascular Disorders/*complications/diagnosis/radiography;Cognition Disorders/*epidemiology/etiology;Cohort Studies;Dementia/epidemiology/etiology;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Risk Factors;Severity of Illness Index;Tomography, X-Ray Computed","Schmidt, R.;Mechtler, L.;Kinkel, P. R.;Fazekas, F.;Kinkel, W. R.;Freidl, W.",1993,,,0,
1404,Magnetic Resonance Imaging of the Brain in Diabetes: The Cardiovascular Determinants of Dementia (CASCADE) Study,"Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.",,"Schmidt, R.;Launer, L. J.;Nilsson, L. G.;Pajak, A.;Sans, S.;Berger, K.;Breteler, M. M.;De Ridder, M.;Dufouil, C.;Fuhrer, R.;Giampaoli, S.;Hofman, A.",2004,March,,0,
1405,Subcortical vascular cognitive impairment: Similarities and differences with multiple sclerosis,"Subcortical vascular cognitive impairment is caused by lacunes and widespread ischemic white matter damage which closely resembles white matter abnormalities seen in multiple sclerosis. Recent evidence suggests that the progression rate of ischemic white matter lesions on MRI is very similar to that observed in multiple sclerosis. Consequently, it has been proposed to use MRI for monitoring disease activity not only in multiple sclerosis but also in vascular dementia trials. There is first evidence from magnetization transfer imaging studies that other than in MS normal appearing white matter is not affected in cerebral small vessel disease. This contrasts the hypothesis that ischemic white matter damage extends far beyond changes visible on conventional MR. The cognitive consequences of both diseases are strikingly similar which is at least partly caused by damage to frontal-subcortical circuits. Involvement of these common functional anatomical structures and their modulatory transmitter systems has now led to common interventional approaches such as the use of cholinesterase inhibitors. © 2006 Elsevier B.V. All rights reserved.",,"Schmidt, R.;Enzinger, C.;Ropele, S.;Schmidt, H.;Fazekas, F.",2006,15,,0,
1406,"White matter lesion progression in LADIS: frequency, clinical effects, and sample size calculations","BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. RESULTS: WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. CONCLUSIONS: WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure.","Aged;Aged, 80 and over;Cognition Disorders/diagnosis/ epidemiology;Disability Evaluation;Disease Progression;Female;Follow-Up Studies;Humans;Leukoaraiosis/diagnosis/ pathology;Leukoencephalopathies/diagnosis/ pathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Outcome Assessment (Health Care);Prevalence;Prognosis;Sample Size","Schmidt, R.;Berghold, A.;Jokinen, H.;Gouw, A. A.;van der Flier, W. M.;Barkhof, F.;Scheltens, P.;Petrovic, K.;Madureira, S.;Verdelho, A.;Ferro, J. M.;Waldemar, G.;Wallin, A.;Wahlund, L. O.;Poggesi, A.;Pantoni, L.;Inzitari, D.;Fazekas, F.;Erkinjuntti, T.",2012,Oct,10.1161/strokeaha.112.662593,0,
1407,"Comparison of magnetic resonance imaging in Alzheimer's disease, vascular dementia and normal aging","MRI scans of 27 patients with probable Alzheimer's disease (mean age 68.2 years), 31 patients with vascular dementia (mean age 69.9 years) and 18 normal controls (mean age 66.3 years) were compared to evaluate possible distinguishing parenchymal abnormalities among these groups. Atrophy was quantitated by subjective rating, linear and volumetric measurements. A number of findings were significantly more common in vascular dementia than in the other subsets. These included (1) basal ganglionic/thalamic hyperintense foci, (2) thromboembolic infarctions, (3) confluent white matter and (4) irregular periventricular hyperintensities. Signal abnormalities on intermediate T(2)-weighted scans in the uncal-hippocampal or insular cortex were frequently and almost exclusively noted in Alzheimer's disease. Moderate and severe cortical and ventricular atrophy and a third ventricular to intracranial width ratio larger than 7% were good discriminators between demented groups and normally aging controls. Selective atrophy measurements, however, failed to separate dementia syndromes. These results suggest that MRI has the potential to increase the accuracy of the clinical diagnosis of Alzheimer's disease and vascular dementia.",,"Schmidt, R.",1992,1992,,0,
1408,Clinical and imaging diagnostics of Parkinson's disease and multiple system atrophy,"The diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA) is primarily made by clinical symptoms, but might still remain challenging even for experienced neurologists. Neuroradiologic imaging may be a useful tool in the diagnostic work-up, particularly for excluding other diseases, such as normal pressure hydrocephalus, multi-infarct dementia and cerebellar lesions. Nuclear medicine methods can additionally support the diagnosis and differential diagnosis of PD and MSA.",,"Schmidt, K. I.;Spiegel, J.;Reith, W.",2011,Apr,,0,
1409,Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease,"Cerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3′-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n=888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P=0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3′-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently predicted six of the non-synonymous single nucleotide polymorphisms (H170R, P496L, V1183M, L1518M, D1823N and V1952M) to be functional, with four being exclusively or mainly detected in subjects with severe white matter lesions. In four individuals with rare non-synonymous single nucleotide polymorphisms, we noted anterior temporal lobe hyperintensity, hyperintensity in the external capsule, lacunar infarcts or subcortical lacunar lesions. None of the observed abnormalities were specific to cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. This is the first comprehensive study investigating (i) the frequency of NOTCH3 variations in community-dwelling elderly and (ii) their effect on cerebral small vessel disease related magnetic resonance imaging phenotypes. We show that the NOTCH3 gene is highly variable with both common and rare single nucleotide polymorphisms spreading across the gene, and that common variants at the NOTCH3 gene increase the risk of age-related white matter lesions in hypertensives. Additional investigations are required to explore the biological mechanisms underlying the observed association. © 2011 The Author.",,"Schmidt, H.;Zeginigg, M.;Wiltgen, M.;Freudenberger, P.;Petrovic, K.;Cavalieri, M.;Gider, P.;Enzinger, C.;Fornage, M.;Debette, S.;Rotter, J. I.;Ikram, M. A.;Launer, L. J.;Schmidt, R.",2011,November,,0,
1410,Apolipoprotein E e4 allele in the normal elderly: neuropsychologic and brain MRI correlates,"The presence of the apolipoprotein E e4 allele has been considered to be a risk factor for Alzheimer's disease and vascular dementia. We therefore used demanding neuropsychologic testing and brain MRI to determine if elderly normals with at least one e4 allele demonstrate subclinical changes in cognition and a higher frequency of brain atrophy or silent ischemic brain damage. The study population consisted of 214 randomly selected individuals aged 50 to 75 years without neuropsychiatric or general disease. There were 175 (81.8%) subjects without and 39 (18.2%) with at least one e4 allele. The two groups were comparable for age, length of education, verbal intelligence, mood and major vascular risk factors. Apolipoprotein E e4 carriers performed significantly worse than non-carriers when assessed for learning and memory abilities, while there were no differences in test results of conceptualization, attention, speed of mental processing and visuopractical skills. There were no between-group differences for thromboembolic and lacunar infarcts, white matter hyperintensity grading and the semiautomatically measured white matter hyperintensity area. The extent of sulcal and ventricular widening as well as hippocampal and parahippocampal volumes were also similar between the comparative subsets. We conclude that the apolipoprotein E e4 allele is associated with subtle learning and memory deficits in normal elderly persons and may therefore be suggested a marker for accelerated cognitive aging. In this group of subjects it was not associated with brain parenchymal changes as demonstrated by MRI.",Aged;*Alleles;Apolipoprotein E4;Apolipoproteins E/*genetics;Brain/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Neuropsychological Tests,"Schmidt, H.;Schmidt, R.;Fazekas, F.;Semmler, J.;Kapeller, P.;Reinhart, B.;Kostner, G. M.",1996,Nov,,0,
1411,Genetics of subcortical vascular dementia,"Subcortical vascular dementia or cerebral small vessel disease is a common cause of disability in the elderly. On magnetic resonance imaging the disease is manifested as white matter lesions, lacunes and microbleeds. Its etiology is complex, with age and hypertension as established risk factors. The heritability of white matter lesions is constantly high over different populations. Linkage studies identified several loci for these lesions however no genes responsible for the linkage signals had been identified so far. Results from genetic association studies using the candidate gene approach support the role of APOE, the renin-angiotensin system, as well as the Notch3 signaling pathway in the development of subcortical vascular dementia. The recent genomegenome wide association study on white matter lesions identified a novel locus on chromosome 17q25 harboring several genes such as TRIM65 and TRIM47 which pinpoints to possible novel mechanisms leading to these lesions. © 2012 Elsevier Inc.",,"Schmidt, H.;Freudenberger, P.;Seiler, S.;Schmidt, R.",2012,November,,0,
1412,"Adrenoleukodystrophy in adult female. A clinical, morphological, and neurochemical study","A 43-year-old female with adrenoleukodystrophy (ALD) is described, who developed spastic tetraparesis, suffered grand mal seizures, and became stuporous and demented during the last 5 years of her life. Computed tomography revealed symmetrical hypodense lesions in the peritrigonal regions. Adrenal insufficiency was not evident except for skin pigmentation. The ultrastructure of a rectal biopsy specimen showed inclusions with lamellae and interspersed clefts in macrophages of the submucosal layer. At autopsy, the adrenals were found to contain large foam cells filled with similar inclusions. The brain cortex and the spinal cord were histologically normal. However, cerebral white matter exhibited widespread demyelination which spared only the arcuate fibres. In regions of less severe demyelination scattered inflammatory cells were seen. On electron microscopy, aggregates of typical paired leaflets with distinct intermediate lines were demonstrated in perivascular macrophages. Histochemical study showed these cells to contain free as well as esterified cholesterol. Gas chromatographic analysis of very long chain fatty acids (VLFA) from the demyelinated cerebral white matter showed a marked increase of C26:0 fatty acid in cholesterol esters and above-normal values for C24:0 and C24:1 in gangliosides. It is suggested that the condition was a heterozygote form of X-linked ALD. Patients with neurodegenerative symptoms with or without adrenal insufficiency can easily be screened for X-linked ALD by VLFA analysis in blood or cultured fibroblasts.",adrenal insufficiency;adrenoleukodystrophy;adult;autopsy;case report;dementia;demyelination;female;heredity;histology;human;priority journal;seizure;spasticity,"Schlote, W.;Molzer, B.;Peiffer, J.;Poremba, M.;Schumm, F.;Harzer, K.;Schnabel, R.;Bernheimer, H.",1987,,,0,
1413,"Progressive multifocal leukoencephalopathy: Three patients diagnosed by brain biopsy, with prolonged survival in two","Since 1980, three immunocompromised patients have been proved to have progressive multifocal leukoencephalopathy (PML) by brain biopsy at the University of Alabama at Birmingham. Two patients presented with focal neurological findings, and the third presented with dementia. Computed tomography (CT) revealed white matter low density lesions in areas appropriate to the neurological abnormalities. Brain biopsy of areas that were abnormal on CT produced diagnostic tissue in all three patients. No patient suffered ill effects from the biopsy. Neuropathological findings on light microscopy were compatible with PML in each case, although there was diversity within the group. Involvement of gray and white matter was present in all biopsy specimens; oligodendrocytes, astrocytes, and neurons were affected. Electron microscopic demonstration of particles compatible with polyoma virus confirmed the diagnosis in each case. Immunosuppressive medication was discontinued in two of the patients; these two have survived more than 2 years after diagnosis. One of these two has gradually improved and is independent in simple activities of daily life. Brain stem and cerebellar involvement and seizure disorders have been present in all reported cases. PML can be accurately and rapidly diagnosed by brain biopsy, enabling therapeutic manipulations that may prolong survival.",brain biopsy;case report;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;electron microscopy;histology;human;immunosuppressive treatment;priority journal;progressive multifocal leukoencephalopathy,"Schlitt, M.;Morawetz, R. B.;Bonnin, J.",1986,,,0,
1414,Plasma lipids and cerebral small vessel disease,"Objectives: We examined the cross-sectional association between lipid fractions and 2 MRI markers of cerebral small vessel disease, white matter hyperintensity volume (WMHV) and lacunes, representing powerful predictors of stroke and dementia. Methods: The study sample comprised 2,608 participants from the 3C-Dijon Study (n 5 1,842) and the Epidemiology of Vascular Aging Study (EVA) (n = 766), 2 large French population-based cohorts (72.8 ± 4.1 and 68.9 ± 3.0 years; 60.1% and 58.4% women, respectively). Analyses were performed separately in each study and combined using inverse variance meta-analysis. Lipid fractions (triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol) were studied as continuous variables. WMHV was studied both in a continuous and dichotomous manner, the latter reflecting the age-specific top quartile of WMHV (EXT-WMHV). Analyses were adjusted for age and sex. Results: Increasing triglycerides were associated with larger WMH Vin the 3C-Dijon Study (β ± SE5 0.0882 ± 0.0302, p = 0.0035), in the EVA Study (β ± SE = 0.1062 ± 0.0461, p = 0.021), and in the combined analysis (β ± SE = 0.0936 ± 0.0252, p = 0.0002) and with higher frequency of lacunes in the 3C-Dijon Study (odds ratio [OR] 5 1.65 [95% confidence interval 1.10-2.48], p 5 0.015), in the EVA Study (OR 5 1.58 [95% confidence interval 0.93-2.70], p 5 0.09), and in the combined analysis (OR51.63 [95%confidence interval 1.18-2.25], p50.003). Associations were attenuated but maintained after adjusting for other vascular risk factors or for inflammatory markers. Associations were present and in the same direction both in participants taking and those not taking lipid-lowering drugs but tended to be stronger in the former for EXT-WMHV. Increasing low-density lipoprotein cholesterol tended to be associated with a decreased frequency and severity of all MRI markers of cerebral small vessel disease in both studies. Conclusions: Increasing triglycerides but not other lipid fractions were associated with MRI markers of cerebral small vessel disease in older community persons.",antilipemic agent;high density lipoprotein cholesterol;low density lipoprotein cholesterol;triacylglycerol;article;cerebrovascular accident;cerebrovascular disease;cognitive defect;cohort analysis;human;lipid blood level;meta analysis;nuclear magnetic resonance imaging;priority journal;risk factor;white matter,"Schilling, S.;Tzourio, C.;Dufouil, C.;Zhu, Y.;Berr, C.;Alpérovitch, A.;Crivello, F.;Mazoyer, B.;Debette, S.",2014,,,0,
1415,Childhood ataxia with diffuse central nervous system hypomyelination,"A significant number of patients with progressive leukodystrophy do not have a definitive diagnosis. This report describes the clinical, morphological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had normal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was present on computed tomography and magnetic resonance scans obtained early in the course of the illness. Dementia was not present and peripheral nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light and electron microscopy of open-brain biopsy specimens from 2 girls showed selective white matter abnormalities including hypomyelination, demyelination, and gliosis. Myelin-specific proteins in the subcortical white matter were examined immunocytochemically and by Western blot analysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysis revealed decreased levels of characteristic myelin lipids. When examined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in white matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.",,"Schiffmann, R.;Moller, J. R.;Trapp, B. D.;Shih, H. H. L.;Farrer, R. G.;Katz, D. A.;Alger, J. R.;Parker, C. C.;Hauer, P. E.;Kaneski, C. R.;Heiss, J. D.;Kaye, E. M.;Quarles, R. H.;Brady, R. O.;Barton, N. W.",1994,March,,0,
1416,Validating the DemTect with 18-fluoro-2-deoxy-glucose positron emission tomography as a sensitive neuropsychological screening test for early alzheimer disease in patients of a memory clinic,"OBJECTIVES: The first study to validate the diagnostic value of the DemTect, a short neuropsychological screening test for dementia (8-10 min), using 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in patients of a memory clinic. METHODS: DemTect results were compared to the clinical diagnosis and to FDG-PET as a reference method for the early in vivo detection of Alzheimer's disease (AD). Results: 38 patients (age 65.2 +/- 9.8 years, 16 men, 22 women) were investigated using clinical standard examination, FDG-PET, and cranial magnetic resonance imaging. According to NINCDS-ADRDA and Petersen's criteria, 18 patients had dementia of the Alzheimer type (DAT) and 13 patients received the diagnosis of mild cognitive impairment (MCI). Compared to the clinical diagnosis, a DemTect cutoff score of < or =11 points demonstrated good sensitivity (83.3%) and specificity (70.0%) for the detection of DAT, whereas the best cutoff score for MCI was < or =13 points with comparable sensitivity (84.6%) and specificity (85.7%). With regard to FDG-PET, the DemTect demonstrated excellent sensitivity (93%) and low specificity (50%) for the detection of AD-typical patterns of cerebral glucose metabolism (cutoff < or =13 points). CONCLUSION: DemTect is a favorable neuropsychological screening instrument for detecting cognitive dysfunction even in predementia stages of AD. For definite cross-sectional diagnosis, further diagnostic evaluation with higher specificity, e.g. comprehensive neuropsychological examination, FDG-PET or other biomarkers, is necessary.","Alzheimer Disease [diagnosis] [psychology] [radionuclide imaging];Cognition [physiology];Data Interpretation, Statistical;Fluorodeoxyglucose F18;Infarction, Middle Cerebral Artery [psychology] [radionuclide imaging];Memory [physiology];Mental Recall [physiology];Neuropsychological Tests;Positron-Emission Tomography;ROC Curve;Radiopharmaceuticals;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Scheurich, A.;Muller, M. J.;Siessmeier, T.;Bartenstein, P.;Schmidt, L. G.;Fellgiebel, A.",2005,,10.1159/000088248,0,
1417,Cerebral hypoperfusion during carotid artery stenosis can lead to cognitive deficits that may be independent of white matter lesion load,"Studies investigating cognitive impairment in stroke-free patients with carotid artery stenosis have led to inconsistent results. Furthermore, the pathophysiological mechanism leading to cognitive impairment remains unclear. Cerebral hypoperfusion and arterio-arterial microembolization are discussed. The aims of our study were (1) to delineate patterns of cognitive impairment in stroke-free patients with carotid artery stenosis and (2) to investigate if cognitive impairment is independent of white matter lesion load in brain MRI. We identified 212 (93 women, mean age 70.2) stroke free, non-demented patients, who were referred for carotid artery stenting or because of subjective cognitive impairment. All patients completed a neurocognitive test battery measuring verbal fluency, constructional praxis, figural memory, verbal short-term- and long-term-memory, verbal recognition memory, semantic processing, speed of cognitive processing and divided attention. Grade of maximum carotid artery stenosis was categorized into three groups (mild, moderate, or severe). White matter lesion load was graded using a visual rating scale. Cognitive test scores of groups with different grades of carotid artery stenosis were compared. Univariate regression analysis was used to measure the predictive value of carotid artery stenosis. Multivariate logistic regression analysis was performed when integrating carotid artery stenosis and white matter lesion load. Carotid artery stenosis negatively correlated with measures of verbal fluency, constructional praxis, verbal short-termmemory, semantic processing, speed of cognitive processing, and divided attention. After adjustment for white matter lesions, carotid artery stenosis did not independently predict divided attention. Significance persisted in all other cognitive domains. In our selected group of patients, a higher grade of carotid artery stenosis is associated with cognitive decline. This process is independent of white matter lesion load. Possible pathophysiological implications are discussed. © 2012 Bentham Science Publishers.",aged;article;attention;brain perfusion;carotid artery obstruction;cognitive defect;correlation analysis;human;long term memory;major clinical study;neuroimaging;nuclear magnetic resonance imaging;predictive value;priority journal;retrospective study;semantics;short term memory;verbal behavior;verbal memory;visual memory;white matter lesion,"Scherr, M.;Trinka, E.;McCoy, M.;Krenn, Y.;Staffen, W.;Kirschner, M.;Bergmann, H. J.;Mutzenbach, J. S.",2012,,,0,
1418,Neuropsychiatric symptoms and brain structural alterations in Fabry disease,"BACKGROUND: Neuropsychiatric symptoms (NPS), mainly cognitive deficits up to dementia and depressive syndromes have been described repeatedly in Fabry disease (FD). However, examinations regarding the pattern, extent, and frequency of the NPS in FD are still lacking. Moreover, the relationship between NPS and brain structural alterations in FD is unknown. The aim of this study was 1) to characterize NPS in a relatively large cohort of adult subjects with FD, and 2) to explore the association of cognitive performance and depressive syndromes with the FD-typical brain structural findings. METHODS: Twenty-five Fabry patients (age 36.5 +/- 11.0) with mild to moderate disease involvement and 20 age, gender-, and education-matched healthy controls were extensively studied by neuropsychiatric assessment, structural magnetic resonance imaging, magnetic resonance angiography, and diffusion-tensor imaging. RESULTS: Patients with FD showed deficits only in the attention domain. Clinically relevant depressive syndromes were noted in 60% of the patients. The subgroup of patients with markedly elevated volumes of white matter lesions (not associated with actual stroke; n=7) showed slightly more learning and memory deficits, but no higher depression rate compared to less affected patients. CONCLUSIONS: Against the prevailing assumption, Fabry patients, even those with marked brain structural alterations, showed only mild cognitive deficits. The high frequency of depression in FD is likely to be related to the burden of this chronic multiorganic hereditary disease, but not to the FD-typical brain structural alterations. Longitudinal studies are necessary to clear, if the mild cognitive deficits in FD might precede clinically relevant cognitive decline.",Adult;Brain/ pathology;Cognition/physiology;Cognition Disorders/pathology;Depression/etiology/pathology;Fabry Disease/ pathology/ psychology;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychotic Disorders/etiology/pathology,"Schermuly, I.;Muller, M. J.;Muller, K. M.;Albrecht, J.;Keller, I.;Yakushev, I.;Beck, M.;Fellgiebel, A.",2011,Feb,10.1111/j.1468-1331.2010.03155.x,0,
1419,Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration,"Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-β(1-42) (Aβ42), tau, and phosphorylated tau concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, and 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer disease, 6 Parkinson disease, and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural magnetic resonance images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD, and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, but not in other diagnostic groups. Analyses in 2 independent FTD cohorts and a group of autopsy-verified or biomarker-enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with the highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. ANN NEUROL 2014;75:116-126 © 2014 Child Neurology Society/American Neurological Association.",,"Scherling, C. S.;Hall, T.;Berisha, F.;Klepac, K.;Karydas, A.;Coppola, G.;Kramer, J. H.;Rabinovici, G.;Ahlijanian, M.;Miller, B. L.;Seeley, W.;Grinberg, L. T.;Rosen, H.;Meredith Jr, J.;Boxer, A. L.",2014,January,,0,
1420,"Chronic pain in ""probable"" vascular dementia: preliminary findings","BACKGROUND: In a previous study, the levels of pain reported by patients with ""possible"" vascular dementia (VaD) were higher than those reported by older individuals without dementia. OBJECTIVE: To examine experienced pain in patients with ""probable"" VaD, confirmed by brain imaging. STUDY DESIGN: Observational, cross sectional. SETTING: Nursing home. METHODS: The participants were 20 nursing home residents (14 females, 6 males) who met the NINDS-AIREN criteria for ""probable"" VaD and 22 nursing home residents with a normal mental status (18 females, 4 males). The patients were in a mild to moderate stage of dementia. All of the participants were suffering from arthritis/arthrosis or osteoporosis. Global cognitive functioning was measured by the Mini-Mental State Examination. Pain was assessed by the Coloured Analogue Scale (CAS: original and modified version) and the Faces Pain Scale. The Geriatric Depression Scale and the Symptom Checklist-90 were used to assess mood. RESULTS: The main finding was that, after controlling for mood, the pain levels indicated by patients with ""probable"" VaD (M = 102.32; standard deviation [SD] = 53.42) were significantly higher than those indicated by the control group (M = 59.17; SD = 38.75), only according to the CAS modified version (F[1,29]) = 5.62, P = 0.01, eta2 = 0.16). CONCLUSION: As VaD patients may experience greater pain than controls, it is essential for prescribers to be aware of the presence of this neuropathology if these patients are to receive adequate treatment.","Aged;Aged, 80 and over;Chronic Pain/ diagnosis/ epidemiology;Cross-Sectional Studies;Dementia, Vascular/ diagnosis/ epidemiology;Female;Homes for the Aged;Humans;Male;Nursing Homes;Pain Measurement/ methods","Scherder, E. J.;Plooij, B.;Achterberg, W. P.;Pieper, M.;Wiegersma, M.;Lobbezoo, F.;Oosterman, J. M.",2015,Mar,10.1111/pme.12637,0,
1421,Small vessel disease and memory loss: What the clinician needs to know to preserve patients' brain health topical collection on stroke,"Small vessel disease (SVD) in the brain manifests in the periventricular and deep white matter and radiographically is described as "" leukoaraiosis"". It is increasingly recognized as a cause of morbidity from middle age onward and this clinical relevance has paralleled advances in the field of neuroradiology. Overall, SVD is a heterogenous group of vascular disorders that may be asymptomatic, or a harbinger of many conditions that jeopardize brain health. Management and prevention focuses on blood pressure control, lifestyle modification, and symptomatic treatment. © 2013 Springer Science+Business Media New York.",acetylsalicylic acid;antihypertensive agent;donepezil;galantamine;memantine;nimodipine;rivastigmine;Alzheimer disease;article;brain atrophy;brain hemorrhage;CADASIL;cerebrovascular disease;chronic kidney disease;cognitive defect;depression;diabetes mellitus;differential diagnosis;Fabry disease;human;hypertension;hypotension;lacunar stroke;leukoaraiosis;lifestyle modification;memory disorder;mental performance;mild cognitive impairment;multiinfarct dementia;neuroimaging;nuclear magnetic resonance imaging;physical activity;Sneddon syndrome;Susac syndrome;vascular amyloidosis;white matter;white matter hyperintensity,"Schenk, C.;Wuerz, T.;Lerner, A. J.",2013,,,0,
1422,High-field magnetic resonance imaging of brain iron in Alzheimer disease,"OBJECTIVES: Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. METHODS: High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. RESULTS: A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.","Aged;Alzheimer Disease/ diagnosis/ metabolism;Biomarkers/metabolism;Brain/ metabolism/pathology;Female;Humans;Image Interpretation, Computer-Assisted/methods;Iron/ metabolism;Iron Metabolism Disorders/diagnosis/metabolism;Magnetic Resonance Imaging/ methods;Male","Schenck, J. F.;Zimmerman, E. A.;Li, Z.;Adak, S.;Saha, A.;Tandon, R.;Fish, K. M.;Belden, C.;Gillen, R. W.;Barba, A.;Henderson, D. L.;Neil, W.;O'Keefe, T.",2006,Feb,10.1097/01.rmr.0000245455.59912.40,0,
1423,Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings,"Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy-pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.","Brain/ pathology;Creutzfeldt-Jakob Syndrome/ genetics/pathology;Electroencephalography;Humans;Magnetic Resonance Imaging;Mutation;Nerve Fibers, Myelinated/pathology;Prions/ genetics","Schelzke, G.;Eigenbrod, S.;Romero, C.;Varges, D.;Breithaupt, M.;Taratuto, A. L.;Kretzschmar, H. A.;Zerr, I.",2011,Apr,10.1016/j.neurobiolaging.2010.11.023,0,
1424,Pathologic findings in a case of primary progressive aphasia,"We report the histopathologic and immunohistochemical findings of a patient who suffered from primary progressive aphasia for 13 years. During the course of his illness, he was diagnosed as having Pick's disease, based on gradually progressive mild personality changes and MRI findings of severe bilateral temporal lobe atrophy. There was severe neuronal loss in the temporal gyri, intense gliosis throughout the cortex, and mild gliosis of the temporal white matter, without any changes typical for Alzheimer's disease or Pick's disease. Using the antibody Alz-50, we found many Alz-50-positive neurons that exhibited a granular or diffuse cytoplasmic stain without fibrous structures in the temporal and parietal cortex, but no ubiquitin or β (A4) protein-reactive cells, nor spongiform changes. Staining for Alz-50 and ubiquitin did not reveal the presence of Pick bodies or Lewy bodies. We consider this case to be an example of nonspecific cortical degeneration. Our findings stress the need for histopathologic verification of the primary progressive aphasia syndrome.",adult;aphasia;article;brain degeneration;case report;histopathology;human;human tissue;immunohistochemistry;male;neuropathology;priority journal,"Scheltens, P.;Ravid, R.;Kamphorst, W.",1994,,,0,
1425,White matter changes on CT and MRI: An overview of visual rating scales,"Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.",adult;Alzheimer disease;article;cognition;computer assisted tomography;human;leukoaraiosis;major clinical study;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;rating scale;risk factor;statistical analysis;symptomatology;white matter,"Scheltens, P.;Erkinjunti, T.;Leys, D.;Wahlund, L. O.;Inzitari, D.;Del Ser, T.;Pasquier, F.;Barkhof, F.;Mäntylä, R.;Bowler, J.;Wallin, A.;Ghika, J.;Fazekas, F.;Pantoni, L.",1998,,,0,
1426,White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer's disease. Evidence for heterogeneity,"In a prospective magnetic resonance imaging (MRI) study we evaluated the prevalence and severity of white matter changes in 29 patients with Alzheimer's Disease (AD) and 24 age-matched healthy elderly, all without cerebrovascular risk factors. The AD patients were divided into two groups according to age at onset of symptoms, one with presenile onset AD (n = 13) and one with senile onset AD (n = 16), who were matched for dementia severity. Signal hyperintensities were rated using a semiquantitative scoring method, separately in the periventricular region (PVH) and in the lobar white matter (WMH), as well as in the basal ganglia (BGH) and in the infratentorial region (ITFH). Cortical atrophy as a parameter of grey matter involvement was rated on a 0 (absent) to 3 (severe) scale. We found PVH, WMH and BGH scores to be significantly higher in senile onset AD patients than in age-matched controls. By means of multiple linear logistic regression we found that PVH, WMH and BGH scores were significantly dependent on the diagnosis of senile onset AD, while the PVH score also showed a significant age dependency. Cortical atrophy did not differ significantly between presenile onset AD and senile onset AD patients. These results indicate that presenile onset AD and senile onset AD patients differ with respect to white matter involvement, but not with respect to grey matter involvement on MRI. Since cerebrovascular risk factors were excluded these findings may indicate that senile onset AD patients display more small vessel involvement (arteriolosclerosis) than presenile onset AD patients, suggesting additional (microvascular) factors for the dementia syndrome in senile onset AD. Our data lend support to the growing body of evidence that AD is heterogeneous, consisting of at least two types. Based on our findings two forms can be distinguished: (i) a 'pure' form of the disease, usually with early disease onset, and no more white matter changes than normal for age; (ii) a 'mixed' form, usually with disease onset later in life, and showing more white matter changes on MRI than normal for age.",Aged;Alzheimer Disease/ diagnosis;Basal Ganglia/pathology;Brain/ pathology;Cerebral Ventricles/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Meninges/pathology;Middle Aged;Prospective Studies,"Scheltens, P.;Barkhof, F.;Valk, J.;Algra, P. R.;van der Hoop, R. G.;Nauta, J.;Wolters, E. C.",1992,Jun,,0,
1427,Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging,"We investigated the histopathologic correlates of white matter changes in Alzheimer's disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRI. White matter changes were rated on a 0 to 3 scale in 51 regions. Histopathologically, we subjectively rated the loss of myelinated axons in the deep and periventricular white matter, denudation of the ventricular ependyma, gliosis, width of the perivascular spaces, and leptomeningeal congophilic angiopathy; we measured structural changes in the walls of the blood vessels in the white matter in micrometers. The AD brains displayed significantly more white matter hyperintensities on MRI than controls. Histopathologically, the denudation of the ventricular ependyma and the gliosis were significantly more severe in AD than in controls, and there was a trend toward more loss of myelinated axons in the deep white matter in the AD brains (p = 0.07). The MRI abnormalities correlated with the loss of myelinated axons in the deep white matter (r' = 0.37; p < 0.01) and with the denudation of the ventricular lining (r' = 0.54; p < 0.01). We could not find any evidence for arteriolosclerosis, but the mean thickness of the adventitia of the arteries of the deep white matter in AD almost doubled the value in control brains (p = 0.0009). We conclude that white matter abnormalities in AD patients and controls consist of loss of myelinated axons, probably caused by arterial changes and breakdown of the ventricular lining. Since imaging/histopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Scheltens, P.;Barkhof, F.;Leys, D.;Wolters, E. C.;Ravid, R.;Kamphorst, W.",1995,May,,0,
1428,A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging,"Differences in grading signal hyperintensities on magnetic resonance imaging may explain earlier reported conflicting results in studies of normal aging and dementia. We designed a new rating scale in which periventricular and white matter signal hyperintensities as well as basal ganglia and infratentorial signal hyperintensities are rated separately in a semiquantative way. In this study we compared the inter- and intra-observer agreements of this scale to the widely used rating scale of Fazekas. We confirmed the poor to reasonable intra- and inter-observer agreements of the Fazekas scale. The new scale, although more elaborate, provided good agreements with respect to the white matter, basal ganglia and infratentorial signal hyperintensities. In rating periventricular hyperintensities this scale yielded no advantage. It is concluded that this scale may be of use in studies especially focussing on deep white matter pathology on MRI, because it provides more detailed information, with good intra- and inter-observer reliability.",Aged;Alzheimer Disease/ diagnosis/pathology;Basal Ganglia/pathology;Brain/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Reference Standards,"Scheltens, P.;Barkhof, F.;Leys, D.;Pruvo, J. P.;Nauta, J. J.;Vermersch, P.;Steinling, M.;Valk, J.",1993,Jan,,0,
1429,White-matter changes on MRI as surrogate marker,"This article reviews the use of white-matter changes as identified on MRI as a surrogate marker in clinical trials on vascular dementia. As of yet, insufficient evidence is present to implement rating or volumetric assessment of the burden of white-matter changes as surrogate marker in such trials, in view of the limited sensitivity to change of current methods and the high measurement error.","Aged;Biomarkers;Brain/*blood supply/*pathology/physiopathology;Cerebrovascular Circulation/physiology;Dementia, Vascular/*pathology/physiopathology;Disease Progression;Humans;*Magnetic Resonance Imaging;Sensitivity and Specificity","Scheltens, P.;Barkhof, F.;Fazekas, F.",2003,,10.1017/s104161020300930x,0,
1430,"Correlation of cognitive status, MRI- and SPECT-imaging in CADASIL patients","Although there is evidence for correlations between disability and magnetic resonance imaging (MRI) total lesion volume in autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the significance of structural MRI abnormalities for cognitive dysfunction remains controversial. We performed detailed neuropsychological testing, high resolution MRI, and Tc-99m-ethyl cysteinate-dimer SPECT in three CADASIL patients. MR-images were rated independently by two investigators for the presence of white matter lesions, lacunar infarcts, microbleeds, and ventricular enlargement. Cortical atrophy was quantified by the use of automatic morphometric assessment of the cortical thickness. In addition, laboratory and patients' history data were collected in order to assess the individual vascular risk factor profile. The differences in cognitive performance between the three patients are neither explained by structural-, or functional neuroimaging, nor by the patient-specific vascular risk factor profiles. The neuroradiologically least affected patient met criteria for dementia, whereas the most severely affected patient was in the best clinical and cognitive state. Conventional structural and functional neuroimaging is important for the diagnosis of CADASIL, but it is no sufficient surrogate marker for the associated cognitive decline. Detailed neuropsychological assessment seems to be more useful, particularly with respect to the implementation of reliable outcome parameters in possible therapeutic trials. © 2006 EFNS.",,"Scheid, R.;Preul, C.;Lincke, T.;Matthes, G.;Schroeter, M. L.;Guthke, T.;Yves Von Cramon, D.;Sabri, O.",2006,April,,0,
1431,Serial quantitative CT analysis of brain morphometrics in adult Down's syndrome at different ages,"Quantitative CT demonstrated increased CSF and 3rd ventricular volumes, and decreased gray matter and white matter volume, in older (greater than 45 years) Down's syndrome (DS) adults with dementia as compared with younger DS adults. Serial CT studies repeated after periods of up to 2 years demonstrated significant progressive cerebral atrophy. Older DS adults without dementia, but with cognitive decline, did not show cerebral atrophy as compared with young DS subjects. These results suggest brain atrophy must be present to accompany dementia in older DS subjects, despite the presence of Alzheimer's disease neuropathology in all older subjects. The Alzheimer's disease process in DS may occur in 2 stages, the 1st with neuropathology and cognitive decline, the 2nd with additional cerebral atrophy and dementia.","Adult;Aging/*physiology;Brain/*radiography;Cross-Sectional Studies;Dementia/complications;Down Syndrome/complications/psychology/*radiography;Female;Humans;Longitudinal Studies;Male;Middle Aged;Neuropsychological Tests;*Tomography, X-Ray Computed","Schapiro, M. B.;Luxenberg, J. S.;Kaye, J. A.;Haxby, J. V.;Friedland, R. P.;Rapoport, S. I.",1989,Oct,,0,
1432,Diffusion-weighted tractography in the common marmoset monkey at 9.4T,"The common marmoset (Callithrix jacchus) is a small New World primate that is becoming increasingly popular in the neurosciences as an animal model of preclinical human disease. With several major disorders characterized by alterations in neural white matter (e.g., multiple sclerosis, Alzheimer's disease, schizophrenia), proposed to be transgenically modeled using marmosets, the ability to isolate and characterize reliably major white matter fiber tracts with MRI will be of use for evaluating structural brain changes related to disease processes and symptomatology. Here, we propose protocols for isolating major white matter fiber tracts in the common marmoset using in vivo ultrahigh-field MRI (9.4T) diffusion-weighted imaging (DWI) data. With the use of a high angular-resolution DWI (256 diffusion-encoding directions) sequence, collected on four anesthetized marmosets, we provide guidelines for manually drawing fiber-tracking regions of interest, based on easily identified anatomical landmarks in DWI native space. These fiber-tract isolation protocols are expected to be experimentally useful for visualization and quantification of individual white matter fiber tracts in both control and experimental groups of marmosets (e.g., transgenic models). As disease models in the marmoset advance, the determination of how macroscopic white matter anatomy is altered as a function of disease state will be relevant in bridging the existing translational gap between preclinical rodent models and human patients.NEW & NOTEWORTHY Although significant progress has been made in mapping white matter connections in the marmoset brain using ex vivo tracing techniques, the application of in vivo virtual dissection of major white matter fiber tracts has been established by few studies in the marmoset literature. Here, we demonstrate the feasibility of whole-brain diffusion-weighted tractography in anesthetized marmosets at ultrahigh-field MRI (9.4T) and propose protocols for isolating nine major white matter fiber tracts in the marmoset brain.",diffusion-weighted imaging;fiber tractography;marmoset,"Schaeffer, D. J.;Adam, R.;Gilbert, K. M.;Gati, J. S.;Li, A. X.;Menon, R. S.;Everling, S.",2017,Aug 1,,0,
1433,Diffusion-weighted imaging as a problem-solving tool in the evaluation of patients with acute strokelike syndromes,"This article addresses syndromes that clinically and/or radiologically resemble acute stroke. These syndromes generally fall into four categories. (1) Patients with acute neurological deficits with nonischemic lesions and no acute abnormality on diffusion-weighted images. These patients may have peripheral vertigo, migraines, seizures, dementia, functional disorders, amyloid angiopathy, or metabolic disorders. When these patients present, we can confidently predict that they are not undergoing infarction. (2) Patients with ischemic lesions with reversible clinical deficits. Nearly 50% of patients with transient ischemic attacks have lesions with restricted diffusion. Patients with transient global amnesia may have punctate lesions with restricted diffusion in the medial hippocampus, parahippocampal gyrus, and corpus callosum. (3) Vasogenic edema syndromes that may mimic acute infarction clinically and on conventional imaging. These include eclampsia/hypertensive encephalopathy, other posterior leukoencephalopathies, human immunodeficiency virus encephalopathy, hyperperfusion syndrome following carotid endarterectomy, venous sinus thrombosis, acute demyelination, and neoplasm. These syndromes demonstrate elevated diffusion rather than the restricted diffusion associated with acute ischemic stroke. (4) Entities in which restricted diffusion may resemble acute infarction. These include pyogenic infections, herpes virus encephalitis, Creutzfeldt-Jakob disease, diffuse axonal injury, tumors with dense cell packing, and rare acute demyelinative lesions.",,"Schaefer, P. W.",2000,2000,,0,
1434,Early small vessel disease affects frontoparietal and cerebellar hubs in close correlation with clinical symptoms--a resting-state fMRI study,"Cerebral small vessel disease, mainly characterized by white matter lesions and lacunes, has a high clinical impact as it leads to vascular dementia. Recent studies have shown that this disease impairs frontoparietal networks. Here, we apply resting-state magnetic resonance imaging and data-driven whole-brain imaging analysis methods (eigenvector centrality) to investigate changes of the functional connectome in early small vessel disease. We show reduced connectivity in frontoparietal networks, whereas connectivity increases in the cerebellum. These functional changes are closely related to white matter lesions and typical neuropsychological deficits associated with small vessel disease.","Brain/blood supply/pathology/ physiopathology;Brain Mapping;Cerebrovascular Disorders/pathology/ physiopathology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Neural Pathways/pathology/ physiopathology","Schaefer, A.;Quinque, E. M.;Kipping, J. A.;Arelin, K.;Roggenhofer, E.;Frisch, S.;Villringer, A.;Mueller, K.;Schroeter, M. L.",2014,Jul,10.1038/jcbfm.2014.70,0,
1435,Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults,"Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long-term memory performance and hippocampal volume in young patients with first-ever ischemic stroke. We studied all consecutive first-ever ischemic stroke patients, aged 18-50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left-hemispheric stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=-0.003, P<0.0001). Longer follow-up duration was associated with smaller ipsilateral hippocampal volume after left-hemispheric stroke (b=-0.028 ml, P=0.002) and right-hemispheric stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life.","Adolescent;Adult;Atrophy/pathology;Brain Ischemia/*complications;Female;Follow-Up Studies;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/etiology/*pathology;*Memory, Episodic;Memory, Long-Term/*physiology;Middle Aged;Stroke/*complications;Young Adult;episodic memory;hippocampal volume;ischemic stroke;young adults","Schaapsmeerders, P.;van Uden, I. W.;Tuladhar, A. M.;Maaijwee, N. A.;van Dijk, E. J.;Rutten-Jacobs, L. C.;Arntz, R. M.;Schoonderwaldt, H. C.;Dorresteijn, L. D.;de Leeuw, F. E.;Kessels, R. P.",2015,Jul,10.1002/hbm.22782,0,
1436,Mediterranean diet and magnetic resonance imaging-assessed cerebrovascular disease,"OBJECTIVE: Cerebrovascular disease is 1 of the possible mechanisms of the previously reported relationship between Mediterranean-type diet (MeDi) and Alzheimer's disease (AD). We sought to investigate the association between MeDi and MRI infarcts. METHODS: High-resolution structural MRI was collected on 707 elderly 65 years or older community residents of New York with available dietary assessments administered an average of 5.8 years (3.22 standard deviations [SDs]) before the MRI. Participants were divided into 3 groups of adherence to MeDi (low, middle, and high tertiles). We examined the association of increasing adherence to MeDi with presence of infarcts on MRI. Models were run without adjustment, adjusted for basic demographic and clinical factors, and adjusted for vascular risk factors. RESULTS: A total of 222 participants had at least 1 infarct. In the unadjusted model, compared to the low adherence group, those in the moderate MeDi adherence group had a 22% reduced odds of having an infarct (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.55-1.14), while participants in the highest MeDi adherence group had a 36% reduced odds (OR, 0.64; 95% CI, 0.42-0.97; p for trend = 0.04). In adjusted models, the association between MeDi adherence and MRI infarcts remained essentially unchanged. The association of high MeDi adherence with infarcts was comparable to that of hypertension (40% reduced probability), did not vary by infarct size or after excluding patients with dementia (n = 46) or clinical strokes (n = 86). There was no association between MeDi and white matter hyperintensities. INTERPRETATION: Higher adherence to the MeDi is associated with reduced cerebrovascular disease burden.","Aged;Aged, 80 and over;Aging/ pathology;Analysis of Variance;Brain/ pathology/physiopathology;Brain Mapping;Cerebrovascular Disorders/ etiology/ pathology/physiopathology;Diet, Mediterranean;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Motor Activity/physiology;Neurologic Examination;Neuropsychological Tests;New York;Risk Factors","Scarmeas, N.;Luchsinger, J. A.;Stern, Y.;Gu, Y.;He, J.;DeCarli, C.;Brown, T.;Brickman, A. M.",2011,Feb,10.1002/ana.22317,0,
1437,Assessment of training efficacy in scoring and reporting 18Ffluorbetaben pet imaging,"Amyloid imaging by PET (Amy-PET) can assist in the early and accurate diagnosis of Alzheimer disease and other dementias. Training for accurate image interpretation is essential for clinical use. Current clinical method for interpretation of 18F-florbetaben (18F-FBB) beta-amyloid PET is visual assessment. Reader training is performed before starting clinical activity and required by Italian Medicines Agency (AIFA). Aim of this work was to test training efficacy, intra- and inter-readers' agreement and compliance in assessing 18F-fluorbetaben PET. METHODS In-person reader training (n=2) and electronic training (n=1) were administered to the medical staff. Training modules were identical in approach and content focused on brain anatomy to identify normal white matter using MRI and coregistered PET images to detect white-gray matter boundaries. Positive scan demonstrates tracer uptake beyond cortical white matter to adjacent gray matter in reference regions. 18F-FBB PET scans were assessed visually by all readers, blinded each other, using a three-grade scoring system comparing regional cortical tracer uptake (RCTU) in gray matter (frontal, parietal and temporal cortex, posterior cingulate cortex/ precuneus) with adjacent white matter. RCTU scores (1 no binding, 2 minor, 3 pronounced) are condensed into a single three-grade scoring system, BAPL score (1 no beta-amyloid load, 2 minor, 3 significant) and BAPLs condensed into a binary interpretation (score 1 negative; 2 or 3 positive). Intra- and inter-reader agreement were assessed by a reevaluation session (30 randomselected images) and Cohens' kappa, compliance by a questionnaire. RESULTS 18F-FBB PET was performed in 83 patients, 82 classified equally by in-person trained readers: 47 B.P. 3, 9 B.P. 2 and 26 B.P. 1. The e-trained reader results were different: 44 B.P. 3, 11 B.P. 2, 28 B.P. 1. RCTUs were classified equally in frontal and parietal regions, different in the precuneus (8 pts) and in the temporal lobe (11 pts) in pts with severe atrophy. Different RCTUs did not change global assessment of amyloid plaque burden (BAPL). Reader's compliance and confidence were evaluated optimal independently from training method. Inter- and intra-reader agreement were excellent (k=0.98) for inperson training group. CONCLUSIONS Results demonstrate good efficacy of the reader training; a supervision seems to be necessary for-etrained staff at starting. Inter- and intra-readers agreement was excellent for global scoring (BAPL) in the in-person trained group. More complex appears regional assessment suggesting the need of a quantitative method particularly necessary when it's critical to establish relationship between anatomy, memory and extra-amnesic disorders and amyloid deposition.",amyloid plaque;anatomy;atrophy;chemical binding;clinical trial;comparative effectiveness;controlled clinical trial;controlled study;frontal cortex;gray matter;human;major clinical study;medical staff;memory;nuclear magnetic resonance imaging;parietal cortex;positron emission tomography;posterior cingulate;precuneus;quantitative analysis;questionnaire;scoring system;single blind procedure;temporal cortex;white matter;amyloid beta protein;endogenous compound;florbetaben;tracer,"Scarlattei, M.;Baldari, G.;Cidda, C.;Migliari, S.;Sammartano, A.;Serreli, G.;Ortenzia, O.;Ghetti, C.;Ruffini, L.",2017,,,0,
1438,Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy,"TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD.","Adult;Atrophy/etiology;Brain/ pathology;Brain Mapping;Cognition Disorders/etiology/pathology;Cohort Studies;Disease Progression;Female;Gait Disorders, Neurologic/etiology/pathology;Humans;Huntington Disease/ complications/ pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Ocular Motility Disorders/etiology/pathology;Psychomotor Disorders/etiology/pathology;Tongue/physiopathology","Scahill, R. I.;Hobbs, N. Z.;Say, M. J.;Bechtel, N.;Henley, S. M.;Hyare, H.;Langbehn, D. R.;Jones, R.;Leavitt, B. R.;Roos, R. A.;Durr, A.;Johnson, H.;Lehericy, S.;Craufurd, D.;Kennard, C.;Hicks, S. L.;Stout, J. C.;Reilmann, R.;Tabrizi, S. J.",2013,Mar,10.1002/hbm.21449,0,
1439,Comparison of brain perfusion SPECT and MRI findings in children with neuronal ceroid-lipofuscinosis and in their families,"Purpose: Neuronal ceroid-lipofuscinoses (NCL) are among the progressive encephalopathies of childhood that are inherited in an autosomal recessive manner. In this study we specifically aimed to investigate any white-matter changes in the carriers (parents) and the healthy siblings of individuals with neuronal ceroid lipofuscinosis disease and whether we may be able to predict the occurrence of any neurological symptoms in healthy children in the future thus enabling early management. Materials and Methods: Since the NCLs are genetically determined diseases, we investigated fifteen individuals in three families that had diseased children of the juvenile type, with brain perfusion SPECT and MRI. Brain perfusion SPECT was performed after administering 222-555 MBq (6-15 mCi) Tc-99m HMPAO intravenously in a dimmed and quiet room. Imaging was performed at least one hour after injection, with a three headed gamma camera equipped with high resolution collimators. A Metz filter (FWHM: 11 mm) was used for processing. Cranial MRI was performed with an imager operating at 1.5 Tesla. Spin-echo T1- and T2-weighted and FLAIR slices were obtained for each individual. Results: In all of the five diseased children we observed pathologic findings both on MRI and Tc-99m HMPAO SPECT. The findings on MRI were mainly features of cerebral and cerebellar atrophy and the observations on Tc-99m HMPAO SPECT were regional perfusion abnormalities. We observed some structural abnormalities on MRI in four of the parents and two of the four healthy siblings. We also noted perfusion abnormalities on Tc-99m HMPAO SPECT in two of the parents and two of the healthy siblings. Conclusion: Because the disease is inherited in an autosomal recessive manner, the parents and the healthy siblings were not supposed to exhibit any demonstrable brain lesions, but the brain perfusion SPECT and MRI examinations clearly revealed multiple lesions in some of the parents and healthy siblings. Detailed neurological examinations of these individuals were normal except for one apparently healthy sibling (EY). Follow-up imaging of these families is being undertaken and further studies are essential in understanding the pathogenesis and genetics of neuronal ceroid-lipofuscinoses.",,"Sayit, E.;Yorulmaz, I.;Bekis, R.;Kaya, G.;Gumuser, F. G.;Dirik, E.;Durak, H.",2002,2002,,0,
1440,Visuomotor integration deficits precede clinical onset in Huntington's disease,"OBJECTIVES: Visuomotor integration deficits have been documented in Huntington disease (HD), with disproportionately more impairment when direct visual feedback is unavailable. Visuomotor integration under direct and indirect visual feedback conditions has not been investigated in the stage before clinical onset ('premanifest'). However, given evidence of posterior cortical atrophy in premanifest HD, we predicted visuomotor integration would be adversely affected, with greater impairment under conditions of indirect visual feedback. METHODS: 239 subjects with the HD CAG expansion, ranging from more than a decade before predicted clinical onset until early stage disease, and 122 controls, completed a circle-tracing task, which included both direct and indirect visual feedback conditions. Measures included accuracy, speed, and speed of error detection and correction. Using brain images acquired with 3T magnetic resonance imaging (MRI), we generated grey and white matter volumes with voxel-based morphometry, and analyzed correlations with circle-tracing performance. RESULTS: Compared with controls, early HD was associated with lower accuracy and slower performance in both circle-tracing conditions. Premanifest HD was associated with lower accuracy in both conditions and fewer rotations in the direct condition. Comparing performance in the indirect condition with the direct condition, HD gene expansion-carriers exhibited a disproportionate increase in errors relative to controls. Premanifest and early HD groups required longer to detect and correct errors, especially in the indirect condition. Slower performance in the indirect condition was associated with lower grey matter volumes in the left somatosensory cortex in VBM analyses. CONCLUSIONS: Visuomotor integration deficits are evident many years before the clinical onset of HD, with deficits in speed, accuracy, and speed of error detection and correction. The visuomotor transformation demands of the indirect condition result in a disproportionate decrease in accuracy in the HD groups. Slower performance under indirect visual feedback was associated with atrophy of the left-hemisphere somatosensory cortex, which may reflect the proprioceptive demands of the task.","Adult;Brain/pathology;Disease Progression;Female;Humans;Huntington Disease/ complications/pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Motor Skills Disorders/complications/ etiology/pathology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Perceptual Disorders/complications/ etiology/pathology;Predictive Value of Tests;Statistics as Topic","Say, M. J.;Jones, R.;Scahill, R. I.;Dumas, E. M.;Coleman, A.;Santos, R. C.;Justo, D.;Campbell, J. C.;Queller, S.;Shores, E. A.;Tabrizi, S. J.;Stout, J. C.",2011,Jan,10.1016/j.neuropsychologia.2010.11.016,0,
1441,Huntington's disease mouse models online: high-resolution MRI images with stereotaxic templates for computational neuroanatomy,"Magnetic resonance imaging (MRI) has proved to be an ideal modality for non-destructive and highly detailed assessment of structural morphology in biological tissues. Here we used MRI to make a dataset of ex vivo brains from two different rodent models of Huntington's disease (HD), the R6/2 line and the YAC 128 mouse. We are making the whole dataset (399 transgenic HD and wildtype (WT) brains, from mice aged 9-80 weeks) publicly available. These data will be useful, not only to investigators interested in the study of HD, but also to researchers of computational neuroanatomy who may not have access to such large datasets from mouse models. Here we demonstrate a number of uses of such data, for example to produce maps of grey and white matter and cortical thickness. As an example of how the library might provide insights in mouse models of HD, we calculated whole brain grey matter volumes across different age groups with different numbers of cytosine-adenine-guanine (CAG) repeats in a fragment of the gene responsible for HD in humans. (The R6/2 dataset was obtained from an allelic series of R6/2 mice carrying a range of CAG repeat lengths between 109 and 464.) This analysis revealed different trajectories for each fragment length. In particular there was a gradient of decreasing pathology with longer CAG repeat lengths, reflecting our previous findings with behavioural and histological studies. There will be no constraints placed on the use of the datasets included here. The original data will be easily and permanently accessible via the University of Cambridge data repository (http://www.dspace.cam.ac.uk/handle/1810/243361).","Animals;Brain/ pathology;Databases, Factual;Disease Models, Animal;Huntington Disease/ pathology;Image Processing, Computer-Assisted;Internet;Magnetic Resonance Imaging;Mice;Mice, Transgenic;Neuroimaging;Neurons/pathology","Sawiak, S. J.;Wood, N. I.;Carpenter, T. A.;Morton, A. J.",2012,,10.1371/journal.pone.0053361,0,
1442,The Cambridge MRI database for animal models of Huntington disease,We describe the Cambridge animal brain magnetic resonance imaging repository comprising 400 datasets to date from mouse models of Huntington disease. The data include raw images as well as segmented grey and white matter images with maps of cortical thickness. All images and phenotypic data for each subject are freely-available without restriction from (http://www.dspace.cam.ac.uk/handle/1810/243361/). Software and anatomical population templates optimised for animal brain analysis with MRI are also available from this site.,"Animals;Cerebral Cortex/pathology;*Databases, Factual;*Disease Models, Animal;Gray Matter/pathology;Humans;Huntington Disease/*pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/*statistics & numerical data;Mice;White Matter/pathology;Mouse models;R6/2;Sheep models","Sawiak, S. J.;Morton, A. J.",2016,Jan 1,10.1016/j.neuroimage.2015.04.056,0,
1443,Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease,"Cerebral white matter lesions, such as leukoaraiosis, may be a result of damage from cerebral ischaemia, and may also be associated with the degenerative process in Alzheimer's disease. The apolipoprotein ε4 (apoε4) genotype is a genetic risk factor for both Alzheimer's disease and ischaemic brain damage through acceleration of atherosclerosis. The aim was to determine whether apoε4 may be related to the formation of cerebral white matter lesions in Alzheimer's disease. The association of apoE genotype, sex, age, and the presence of several vascular risk factors, with the presence of white matter lesions in 55 patients clinically diagnosed with Alzheimer's disease was investigated. The cerebral white matter lesions were identified by T2 weighted MRI and classified on a 4 grade scale from no lesion to diffuse lesion. The odds ratio (OR) of the factors mentioned above to the presence of white matter lesions was determined and tested by Fisher's exact test. The association of the lesion grades with these factors was analysed by non-parametric tests. The apoE 4 genotype was strongly associated with Alzheimer's disease (p = 0.0001), but not associated with the presence or the degree of cerebral white matter lesions in Alzheimer's disease (OR = 1.09, p > 0.99). Aging (> 70 years old) was a significant risk factor for white matter lesions (OR = 7.2, p = 0.0006) and age was significantly correlated with the lesion (p = 0.0075). The OR of female sex to the lesion grades was 2.89 (p = 0.084) and the lesion grade of female sex was significantly higher than that of the male sex (p = 0.047). Other vascular risk factors were not significantly associated with the presence of white matter lesions. These findings suggest that there is a sex difference in white matter pathology in Alzheimer's disease.",apolipoprotein E;age;aged;Alzheimer disease;article;brain injury;controlled study;female;genotype;human;human tissue;major clinical study;male;neuropathology;nuclear magnetic resonance imaging;priority journal;risk assessment;sex difference;statistical analysis;white matter,"Sawada, H.;Udaka, F.;Izumi, Y.;Nishinaka, K.;Kawakami, H.;Nakamura, S.;Kameyama, M.",2000,,,0,
1444,A case of venous dural sinus thrombosis presenting dementia syndrome. An autopsy case,"We report clinical and pathological features of a case of dementia syndrome due to dural sinus thrombosis. In three years before admission, the patient, a 64-year old man, had had four convulsive attacks; scattered calcification shadows were disclosed by plain CT. Ten months before the admission, he complained of progressive memory disturbance and dyscalculia. General physical examination showed no remarkable abnormalities except for bruit at the left mastoid process. Although his time orientation was poor, he was otherwise fully awake. Neurologically, memory disturbance, finger agnosia, and dyscalculia were observed. Right Barré's sign, and exaggerated right patellar tendon reflex were observed. Plain X-ray CT revealed calcification-like, scattered high-density areas in the floor of the cerebral cortical sulci. Enhanced CT showed abnormal vessel high-density areas in both the cerebrum and brainstem. Cerebral angiography showed thrombosis of bilateral transverse sinuses, arterio-venous fistula in the left transverse sinus, and remarkably dilated cortical veins over both cerebral hemispheres. Positron emission tomography revealed misery perfusion areas in bilateral cerebral hemispheres. We presume that the mass effect of venous engorgement and chronic ischemia due to the arterio-venous fistula caused the dementia syndrome. These clinical manifestations were improved by amantadine and the patient was discharged. During follow-up, he died of subarachnoid hemorrhage, and an autopsy was performed. Pathological findings were as follows: 1) cortical and subcortical multiple-infarction in the cerebrum, 2) hematoma in the subarachnoid space, 3) venous dilatation of the cortical veins and pseudocalcification of their walls, and 4) thrombus in the transverse dural sinus.",amantadine;article;brain;calcinosis;case report;cerebral sinus thrombosis;dementia;human;male;middle aged;pathology,"Sawada, H.;Akiguchi, I.;Kimura, T.;Fukuyama, H.;Kameyama, M.",1989,,,0,
1445,Poor outcome associated with probable bilateral extracranial ICA vasospasm,"We describe a woman with bilateral extracranial internal carotid artery (ICA) vasospasm. Initial MRI of the brain showed multiple areas of high-signal intensity in the white matter of both the frontoparietal lobes. She was alert, and the muscle strength of the four extremities was moderately decreased. Cranial CT on day 3 showed increased numbers of low-density areas in both the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA), accompanied by neurological deterioration. Cranial and cervical CT angiography on day 9 showed that all areas of both the ACA and MCA had become low density. Both ICAs were markedly narrowed along their entire length and tapered. On day 16, the patient died. Three patients with bilateral extracranial ICA spasms have been described previously. To our knowledge, this is the first time to document bilateral ICA spasm causing elongated narrowing of the carotid arteries, leading to an unfortunate outcome. Copyright 2013 BMJ Publishing Group. All rights reserved.",argatroban;dexamethasone;heparin;norphenazone;aged;anterior cerebral artery;article;artificial ventilation;Babinski reflex;brain vasospasm;cardiopulmonary arrest;carotid artery obstruction;case report;clinical feature;coma;computed tomographic angiography;contrast enhancement;differential diagnosis;electrocardiography;female;follow up;Holter monitoring;human;internal carotid artery;mental deterioration;neuroimaging;nuclear magnetic resonance imaging;outcome assessment;priority journal;resuscitation;sinus tachycardia;vasculitis,"Sawa, N. N.;Kataoka, H.;Ueno, S.",2013,,,0,
1446,Aging of the adult human brain: In vivo quantitation of metabolite content with proton magnetic resonance spectroscopy,"The purpose of this study was to examine the effect of aging on brain metabolite concentrations, including N-acetyl aspartate (NAA), the major marker of neurones, using short echo proton spectroscopy. Single-voxel proton spectra (TE 30 msec, TR 2 seconds) were obtained from white and gray matter using automated software (PROBE, G.E., Milwaukee, WI). Spectra were analyzed using the variable projection technique. Thirty healthy volunteers were studied within the age range 24-89 years. No significant trend in change of concentrations of NAA, total creatine, total choline or myo-inositol were seen with age. The total creatine concentration of parietal white matter in the over 60 age group (6.5 ± 0.3 mmol/l) was significantly higher than the under 60 age group (6.0 ± 0.4 mmol/1; P < 0.05). No other significant difference between the two age groups was seen. The tissue concentration of the major neuronal marker, NAA, does not decline with age. No age-related changes in the concentrations of choline and myo-inositol and occipital gray matter total creatine were observed. These results provide a normal range of values for spectroscopically detectable metabolites within the regions studied, against which neurological diseases such as Alzheimer's disease can be compared in vivo.",n acetylaspartic acid;aged;aging;Alzheimer disease;article;brain metabolism;brain tumor;cerebrospinal fluid;cerebrovascular disease;clinical article;controlled study;gray matter;human;occipital lobe;priority journal;proton nuclear magnetic resonance;sex difference;white matter;Signa,"Saunders, D. E.;Howe, F. A.;Van Den Boogaart, A.;Griffiths, J. R.;Brown, M. M.",1999,,,0,
1447,A case of intravascular malignant lymphomatosis presenting as cerebral infarction,"A case of intravascular malignant lymphomatosis (IML) presenting as progressive cerebral infarction is reported. A 62-year-old previously healthy male developed progressive dementia. MRI of the brain at the nearest hospital revealed multiple infarcts with unknown etiology. His level of consciousness deteriorated rapidly, and then he was transferred to our hospital for further evaluation. High grade fever, raised serum C reactive protein (CRP), and raised lymphoma markers (serum LDH and soluble IL-2 receptor (sIL-2R)) were observed. Repeated brain MRI disclosed progression of multifocal cerebral infarctions. We considered IML most likely, and we performed muscle biopsy. However muscle biopsy didn't demonstrate any proliferation of neoplastic cells of lymphoid origin within small vessels. Thereafter IML was diagnosed by brain biopsy. The patient underwent chemotherapy, but died of pneumonia due to severe myelosuppression. IML is a rare disease but most commonly shows neurological symptomatology as its clinical manifestation. Dementia is the most common neurological symptom, and progressive multiple infarction is the most common of the MRI findings. Rapidly progressive dementia associated with multiple infarction, when elevated CRP, LDH and sIL-2R are observed in the laboratory data, is suggestive of IML.",C reactive protein;interleukin 2 receptor;lactate dehydrogenase;adult;article;brain biopsy;brain infarction;case report;clinical feature;dementia;disease course;fatality;human;intravascular malignant lymphomatosis;lymphomatosis;male;nuclear magnetic resonance imaging,"Satow, T.;Nabeshima, S.;Yamazoe, N.;Isaka, F.;Motoyama, Y.;Higuchi, K.;Kawamura, Y.;Hayashino, Y.",2000,,,0,
1448,Musical anhedonia: Selective loss of emotional experience in listening to music,"Recent case studies have suggested that emotion perception and emotional experience of music have independent cognitive processing. We report a patient who showed selective impairment of emotional experience only in listening to music, that is musical anhednia. A 71-year-old right-handed man developed an infarction in the right parietal lobe. He found himself unable to experience emotion in listening to music, even to which he had listened pleasantly before the illness. In neuropsychological assessments, his intellectual, memory, and constructional abilities were normal. Speech audiometry and recognition of environmental sounds were within normal limits. Neuromusicological assessments revealed no abnormality in the perception of elementary components of music, expression and emotion perception of music. Brain MRI identified the infarct lesion in the right inferior parietal lobule. These findings suggest that emotional experience of music could be selectively impaired without any disturbance of other musical, neuropsychological abilities. The right parietal lobe might participate in emotional experience in listening to music. © 2011 Psychology Press.",iodine 123;aged;anhedonia;article;brain artery;brain blood flow;brain infarction;case report;dizziness;emotion;emotional disorder;human;intelligence;internal carotid artery occlusion;magnetic resonance angiography;male;memory;Mini Mental State Examination;music;musical anhednia;neuropsychological test;nuclear magnetic resonance imaging;parietal lobe;perception;recognition;scoring system;single photon emission computer tomography;speech audiometry,"Satoh, M.;Nakase, T.;Nagata, K.;Tomimoto, H.",2011,,,0,
1449,White matter activated glial cells produce BDNF in a stroke model of monkeys,"Lacunar-type stroke accounts for approximately a quarter of all ischemic strokes, and is the most common cause of vascular dementia. Despite its importance, there are few specific treatments for lacunar stroke, probably due largely to a lack of animal models. In this study, we developed a stroke model in a higher primate, the Macaque monkey. This was achieved by occluding the deep subcortical penetrating arteries with agarose spheres of mean diameters around 50 microm, and the appropriateness of this model as a lacunar-type stroke was verified by MRI. We observed widespread gliosis in the ipsilateral white matter (WM) of the stroke monkey. We also analyzed the expression of neurotrophins in the activated glial cells, and found that their expression of BDNF was stimulated in the affected WM following ischemic injury. Our results support the idea that WM glial cells play an active role in protecting and promoting the regeneration of nerve fibers in the affected WM of the ischemic brain, by producing BDNF. These findings may be useful for the development of new therapeutic strategies aimed at preventing or treating stroke.","Animals;Astrocytes/*metabolism;Brain Infarction/*metabolism/physiopathology;Brain-Derived Neurotrophic Factor/*metabolism;Disease Models, Animal;Fluorescent Antibody Technique;Glial Fibrillary Acidic Protein/metabolism;Gliosis/metabolism/physiopathology;Internal Capsule/metabolism/physiopathology;Macaca fascicularis;Magnetic Resonance Imaging;Male;Stroke/*metabolism/physiopathology","Sato, Y.;Chin, Y.;Kato, T.;Tanaka, Y.;Tozuka, Y.;Mase, M.;Ageyama, N.;Ono, F.;Terao, K.;Yoshikawa, Y.;Hisatsune, T.",2009,Sep,10.1016/j.neures.2009.05.010,0,
1450,A case of the panencephalopathic type of Creutzfeldt-Jakob disease with retinal involvement,"Neuropathological study of the visual pathway from the retina to the occipital cortex in Creutzfeldt-Jakob disease (CJD) has been scarcely performed. In the present study, pathological involvement of the visual pathway was observed in a 54-year-old man with CJD. The patient had the onset of visual disturbances in December 1985. He subsequently developed progressive dementia, right hemiparesis, ataxia and dysarthria, and rapidly fell into decerebrate posture in February 1986. In March 1986, myoclonus appeared on the whole body and EEG revealed periodic synchronous discharges, while brain CT and CSF findings showed no abnormalities. Myoclonus was observed most frequently from May to October 1986, and then reduced gradually. Brain atrophy on CT started from April 1986, and was progressive till the end stage of the disease. He died in January 1988, and the total clinical course was about 24 months. Neuropathological examination revealed severe degeneration of the cerebral cortex and the white matter. In the cerebral cortex, marked loss of neurons, astrogliosis, and spongiform changes were observed. In the cerebral white matter, the destruction of myelin sheaths and axons were evident. The cerebellum showed prominent loss of granule cells. These findings are consistent with those of the panencephalopathic type of CJD. In the visual pathway, loss of ganglion cells and bipolar cells in the retina, mild demyelination of the optic nerve, neuronal loss in the lateral geniculate body, and severe degeneration in the visual cortex were observed. The present case suggests that the neuropathological investigation in the visual pathway from the retina to the occipital cortex is important for clarifying the pathological processes in the visual system in CJD.",article;brain;case report;Creutzfeldt Jakob disease;human;male;middle aged;pathology;retina;retina disease;visual disorder;visual system,"Sato, Y.;Chiba, S.;Miyagishi, T.",1992,,,0,
1451,Correlation between diffusion tensor tractography and proton MR spectroscopy in normal controls,"Tractography is a procedure that can track and demonstrate the 3D neural tracts of the white matter of the brain. The images of the brain are obtained by analyzing the diffusion tensor, identification of which can provide the anatomical connections of the brain. Studying these connections is integral to the understanding of the brain function. Specifically, the uncinate fasciculus and fornix, which are the white matter in the human brain, are said to be related to cognitive function. The tractography is calculated using diffusion tensor imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia patients is lower than that of healthy individuals. It is also suggested that the DTI parameter of healthy individuals decreases with age. In addition, Proton MR Spectroscopy ((1)H-MRS) is indicative of neuronal damage and has been used for decades as a noninvasive technique for assessing the biochemistry of the human brain. This is reflected by the increasing number of clinical MRS investigations of neurological disorders. Thus, MRS and DTI can provide complementary images on white matter in brain and it is important to investigate the white matter brain changes by simultaneously acquiring DTI and MRS in health control subjects. In this research, we have calculated the correlation coefficient between the DTI parameter of uncinate fasciculus, fornix and (1)H-MRS. Our result shows that the correlation coefficient of DTI parameter and (1)H-MRS of a left fornix is 0.65 at the maximum. Correlation between DTI measurement and (1)H-MRS suggests the relationships between the uncinate fasciculus, fornix and cognitive neuronal function. Our finding matches previous reports on the correlation between DTI parameters and (1)H-MRS.",Adult;Brain/anatomy & histology/ physiopathology;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nervous System Diseases/physiopathology;Protons,"Sato, T.;Maruyama, N.;Hoshida, T.;Minato, K.",2013,,10.1109/embc.2013.6609550,0,
1452,Correlation between uncinate fasciculus and memory tasks in healthy individual using diffusion tensor tractography,"Tractography is a procedure that can track and demonstrate the 3D neural tracts of the white matter of the brain. The images of the brain are obtained by analyzing the diffusion tensor, identification of which can provide the anatomical connections of the brain. Studying these connections is integral to the understanding of the brain function. Specifically, the uncinate fasciculus (UF), which is the white matter in the human brain, is said to be related to cognitive function. The UF tractography is calculated using diffusion tensor imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia patients is lower than that of healthy individuals. It is also suggested that the DTI parameter of healthy individuals decreases with age. In addition, the WMS-R score, which is indicative of general memory, verbal memory and other cognitive functions, of the elderly are lower than of the young. However, there is no report yet that has holistically investigated DTI parameter and the memory functions. Thus, in this research, we have calculated the correlation coefficient between the DTI parameter of UF and WMS-R score. Our result shows that the correlation coefficient of diffusivity of the fiber direction and visual memory of a left UF is -0.226 at the maximum. Correlation between DTI measurement and memory performance suggests the relationships between the UF and function in memory tasks lateralization. Our finding matches previous reports on the correlation between FA in the left, or L1 in the right UF, and performance on visual memory.",adult;algorithm;article;brain;computer assisted diagnosis;diffusion tensor imaging;frontal lobe;hemispheric dominance;histology;human;memory;middle aged;nerve tract;neuropsychological test;physiology;statistics;temporal lobe;young adult,"Sato, T.;Maruyama, N.;Hoshida, T.;Minato, K.",2012,,,0,1453
1453,Correlation between uncinate fasciculus and memory tasks in healthy individual using diffusion tensor tractography,"Tractography is a procedure that can track and demonstrate the 3D neural tracts of the white matter of the brain. The images of the brain are obtained by analyzing the diffusion tensor, identification of which can provide the anatomical connections of the brain. Studying these connections is integral to the understanding of the brain function. Specifically, the uncinate fasciculus (UF), which is the white matter in the human brain, is said to be related to cognitive function. The UF tractography is calculated using diffusion tensor imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia patients is lower than that of healthy individuals. It is also suggested that the DTI parameter of healthy individuals decreases with age. In addition, the WMS-R score, which is indicative of general memory, verbal memory and other cognitive functions, of the elderly are lower than of the young. However, there is no report yet that has holistically investigated DTI parameter and the memory functions. Thus, in this research, we have calculated the correlation coefficient between the DTI parameter of UF and WMS-R score. Our result shows that the correlation coefficient of diffusivity of the fiber direction and visual memory of a left UF is -0.226 at the maximum. Correlation between DTI measurement and memory performance suggests the relationships between the UF and function in memory tasks lateralization. Our finding matches previous reports on the correlation between FA in the left, or L1 in the right UF, and performance on visual memory.",,"Sato, T.;Maruyama, N.;Hoshida, T.;Minato, K.",2012,2012,,0,
1454,Circulating IL-6 and CRP are associated with MRI findings in the elderly: the 3C-Dijon Study,"OBJECTIVE: The relation between inflammation and brain MRI findings in the elderly remains poorly known. We investigated the association of circulating interleukin-6 (IL-6) and C-reactive protein (CRP) levels with baseline and longitudinal white matter hyperintensities (WMH), silent brain infarction, and brain volumes in community-dwelling elderly free of dementia. METHODS: We included 1,841 participants aged 65 to 80 years from the Three City-Dijon cohort. Participants followed an MRI examination at baseline and after a 4-year follow-up (n = 1,316). IL-6 and CRP concentrations were measured at baseline from fasting blood samples. WMH were detected with an automatic imaging processing method and gray matter, hippocampal, white matter, and CSF volumes were estimated with voxel-based morphometry. Silent brain infarctions were assessed visually and defined as focal lesions of >/=3 mm in the absence of stroke. We used analysis of covariance and logistic regression to model the associations between inflammatory biomarkers and brain MRI findings adjusting for potential confounders. RESULTS: In cross-sectional analyses, higher IL-6 levels were associated with higher WMH volumes (p < 0.01), lower gray matter (p = 0.001) and hippocampal (p = 0.01) volumes, and increasing CSF volumes (p = 0.002) in a dose-relationship pattern. Similar but weaker relations were observed for CRP. We observed no associations between baseline inflammatory biomarker levels and the evolution of MRI findings over 4 years. CONCLUSIONS: IL-6, and, to a lesser degree, CRP levels were associated with WMH severity as well as global markers of brain atrophy. These results suggest that an inflammatory process may be involved in both age-associated brain alterations.","Aged;Aged, 80 and over;Atrophy/blood/pathology;Brain/ pathology;C-Reactive Protein/ metabolism;Cross-Sectional Studies;Female;Hippocampus/pathology;Humans;Inflammation/blood/pathology;Interleukin-6/ blood;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology","Satizabal, C. L.;Zhu, Y. C.;Mazoyer, B.;Dufouil, C.;Tzourio, C.",2012,Mar 6,10.1212/WNL.0b013e318248e50f,0,
1455,Inflammatory proteins and the severity of dilated Virchow-Robin spaces in the elderly,"Recent studies suggest dilated Virchow-Robin Spaces (dVRS) could be a manifestation of cerebral small-vessel disease, but little is known about their risk factors. As inflammation has been associated with other brain MRI findings, we investigated whether interleukin-6 and C-reactive protein were associated with the severity of dVRS in the eldery. dVRS were assessed in basal ganglia and white matter and rated on a severity scale. We found that elevated interleukin-6 levels were associated with higher severity of dVRS in basal ganglia, suggesting that inflammation might be associated with the burden of dVRS in the elderly. © 2013 - IOS Press and the authors. All rights reserved.",C reactive protein;interleukin 6;aged;article;basal ganglion;brain blood vessel;brain cortex;cognitive defect;dementia;dilated virchow robin space;female;human;major clinical study;male;priority journal;prospective study,"Satizabal, C. L.;Zhu, Y. C.;Dufouil, C.;Tzourio, C.",2013,,,0,
1456,Optimal segmentation of brain MRI based on adaptive bacterial foraging algorithm,"Segmentation of brain magnetic resonance images (MRIs) can be used to identify various neural disorders. The MRI segmentation facilitates in extracting different brain tissues such as white matter, gray matter and cerebrospinal fluids. Segmentation of these tissues helps in determining the volume of the tissues in three-dimensional brain MRI, which yields in analyzing many neural disorders such as epilepsy and Alzheimer disease. In this article, multilevel thresholding based on adaptive bacterial foraging (ABF) algorithm is presented for brain MRI segmentation. The proposed ABF algorithm employs an adaptive step size to improve both exploration and exploitation capability of the BF algorithm. Maximization of the measure of separability on the basis of the entropy (Kapur) method and the between-class variance (Otsu) method, which are the two popular thresholding techniques, are employed to evaluate the performance of the proposed method. Application results to axial, T2-weighted brain MRI slices are provided to show the performance of the proposed segmentation approach. These results are compared with bacterial foraging (BF) algorithm, particle swarm optimization (PSO) algorithm and genetic algorithm (GA) in terms of solution quality, robustness and computational efficiency. © 2011 Elsevier B.V.",,"Sathya, P. D.;Kayalvizhi, R.",2011,July,,0,
1457,Acute confusional migraine may be a presenting feature of CADASIL,"OBJECTIVE: Characterize the phenomenon of acute confusional migraine (ACM) among Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients and emphasize the possibility of CADASIL in adults with ACM. BACKGROUND: ACM, well described in children, has rarely been reported in adults. Although 30-60% of CADASIL patients have migraine, acute confusional state during migraine has not been described. We describe 7 patients with ACM that complicated up to 50% of the migraine episodes. DESIGN/METHODS: Detailed neurologic evaluation was performed in 20 CADASIL patients; International Classification of Headache Disorders 2nd edition criteria were used to diagnose migraine. RESULTS: The mean age was 51 years. Fourteen patients reported headache and 11 met the criteria for migraine (mean age of onset 25). Seven patients experienced concomitant confusion, within 3 years of migraine onset. Confusion occurred either abruptly or insidiously, at the onset of aura or headache, lasting for 2-48 hours, and ending abruptly. These episodes were stereotypic, characterized by disorientation with agitation, and retrograde amnesia for the episodes. Patients reported disorientation to time and place, inability to recognize friends and relatives, difficulty with finding directions home, fear of getting lost, inability to analyze traffic lights or tell time. Patients reliably predicted the episodes and felt the need to seek a safe place for protection. Severity of the episodes progressed, but a striking improvement occurred after the first stroke. CONCLUSION: ACM may be a presenting feature and important clue, enabling CADASIL to be recognized up to a decade or earlier than at present. Therefore, a brain MRI and/or testing for Notch3 mutations should be considered in adult patients with ACM.",Adult;Aged;CADASIL/*complications;Epilepsy/complications/diagnosis;Female;Headache/complications/diagnosis;Humans;Male;Middle Aged;Migraine Disorders/*complications/*diagnosis;Neurologic Examination,"Sathe, S.;DePeralta, E.;Pastores, G.;Kolodny, E. H.",2009,Apr,10.1111/j.1526-4610.2009.01363.x,0,
1458,Migraine and neurogenetic disorders,"In the current classification of headache disorders, headache attributable to genetic disorders is not classified separately, rather as headache attributed to cranial or cervical vascular disorder. The classification thus implies that a vascular pathology causes headache in these genetic disorders. Unquestionably, migraine is one of the prominent presenting features of several genetic cerebral small vessel diseases such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, retinal vasculopathy with cerebral leukodystrophy, and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty. Shared genetic features, increased susceptibility, and/or vascular endothelial dysfunction may play a role in pathogenesis of migraine. Common or overlapping pathways involving the responsible genes may provide insight regarding the pathophysiological mechanisms that can explain their comorbidity with migraine. This review focuses on clinical features of genetic vasculopathies. An independent category - migraine related to genetic disorders - should be considered to classify these disorders. © 2013 Springer Science+Business Media New York.",Notch3 receptor;adult;amino acid substitution;article;CADASIL;case report;dementia;disease classification;family history;female;headache;human;magnetic resonance angiography;multiple sclerosis;notch3 gene;nuclear magnetic resonance imaging;photophobia;sequence analysis;vomiting;white matter lesion,"Sathe, S.",2013,,,0,
1459,"Two autopsy cases with Pelizaeus-Merzbacher disease phenotype of adult onset, without mutation of proteolipid protein gene","We report the autopsy cases of two brothers which are pathologically compatible with Pelizaeus-Merzbacher disease (PMD). Both patients had a late onset (at the ages of 29 and 42 years) and chronic neurological symptoms including tremor, ataxia and dementia. The T2-weighted magnetic resonance imaging of the younger brother demonstrated increased signal areas with sparing of small areas in the cerebral white matter. The postmortem examinations, obtained at the ages of 45 and 61 years, showed similar neuropathological findings. Histologically, a cardinal finding was a lack of myelin in large parts of white matter with the preservation of islands of intact myelin, resulting in a 'tigroid' appearance. Only small amounts of sudanophilic material were present. The axons were relatively well preserved, but oligodendrocytes were numerically reduced. Ultrastructurally, myelin sheaths in the white matter were markedly thin. Immunohistochemistry showed that proteolipid protein (PLP) was reduced in the affected white matter. However, genetic studies did not reveal exonic mutations or duplications of the PLP gene. We conclude that the two cases are a rare type of dysmyelinating disorder with PMD phenotype of adult onset and could be caused by previously unrecognized abnormalities of the PLP gene or other genes.",,"Sasaki, A.;Miyanaga, K.;Ototsuji, M.;Iwaki, A.;Iwaki, T.;Takahashi, S.;Nakazato, Y.",2000,January,,0,
1460,An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease,"INTRODUCTION: Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB). METHODS: White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort. RESULTS: DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia. DISCUSSION: In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/diagnostic imaging/pathology;Brain Infarction/etiology;Case-Control Studies;Cerebrovascular Disorders/ etiology/ pathology;Cohort Studies;Female;Humans;Lewy Body Disease/ complications/diagnostic imaging/pathology;Magnetic Resonance Imaging;Male;Middle Aged;White Matter/diagnostic imaging/ pathology;Alzheimer's disease;Cerebrovascular disease;Dementia with Lewy bodies;Infarcts;Mri;Sex differences;White matter hyperintensities","Sarro, L.;Tosakulwong, N.;Schwarz, C. G.;Graff-Radford, J.;Przybelski, S. A.;Lesnick, T. G.;Zuk, S. M.;Reid, R. I.;Raman, M. R.;Boeve, B. F.;Ferman, T. J.;Knopman, D. S.;Comi, G.;Filippi, M.;Murray, M. E.;Parisi, J. E.;Dickson, D. W.;Petersen, R. C.;Jack, C. R., Jr.;Kantarci, K.",2017,Mar,,0,
1461,An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease,"INTRODUCTION: Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB). METHODS: White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort. RESULTS: DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia. DISCUSSION: In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.",Alzheimer's disease;Cerebrovascular disease;Dementia with Lewy bodies;Infarcts;Mri;Sex differences;White matter hyperintensities,"Sarro, L.;Tosakulwong, N.;Schwarz, C. G.;Graff-Radford, J.;Przybelski, S. A.;Lesnick, T. G.;Zuk, S. M.;Reid, R. I.;Raman, M. R.;Boeve, B. F.;Ferman, T. J.;Knopman, D. S.;Comi, G.;Filippi, M.;Murray, M. E.;Parisi, J. E.;Dickson, D. W.;Petersen, R. C.;Jack, C. R., Jr.;Kantarci, K.",2016,Aug 10,10.1016/j.jalz.2016.07.003,0,1460
1462,Whole genome sequence analyses of brain imaging measures in the Framingham Study,"OBJECTIVE: We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program. METHODS: We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants. RESULTS: We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10(-8)) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 x 10(-8)). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 x 10(-4)) and in 17q25 for WMH (rs7214628, p = 2.0 x 10(-3)) were confirmed. Gene-based tests detected associations (p </= 2.3 x 10(-6)) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- (UNC5D) and Parkinson disease-associated genes (GBA). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways. CONCLUSIONS: Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings.",,"Sarnowski, C.;Satizabal, C. L.;DeCarli, C.;Pitsillides, A. N.;Cupples, L. A.;Vasan, R. S.;Wilson, J. G.;Bis, J. C.;Fornage, M.;Beiser, A. S.;DeStefano, A. L.;Dupuis, J.;Seshadri, S.;Consortium, Nhlbi Trans-Omics for Precision Medicine;Group, T. OPMed Neurocognitive Working",2018,Jan 16,,0,
1463,Morphogenesis timing of genetically programmed brain malformations in relation to epilepsy,"Cerebral malformations are best understood as abnormal tissue morphogenesis in the context of disorders of ontogenesis. In neuroembryology, the timing of onset and duration of abnormal genetic expression and neurodevelopmental processes are primordial and must always be assessed, regardless whether the dysgenesis is primarily genetic in origin or acquired in utero due to ischemia, fetal infarcts that interrupt cellular migration or exposure to teratogenic drugs or neurotoxins. Defective timing interferes with the synchrony between different developmental processes, such as synaptogenesis in relation to other aspects of neuronal maturation. Timing may be delay or arrest development at an immature stage or may be precocious but asynchronous with other developmental features. Focal cortical dysplasia (FCD) types 1 and 3 may be arrested maturation of the radial microcolumnar neocortical architecture that is normal in the first half of gestation, without the expected transition to a horizontal or tangential laminar cortical architecture in the second half. Lack of lamination in either the vertical or horizontal planes may be due to defective extracellular adhesion molecules that cause detachment of migratory neuroblasts from their radial glial guide fibers, to enable recently arriving neuroblasts to bypass those already in place within the cortical plate for the programmed inside-out neuronal arrangement. FCD type 2 has a different pathogenesis. The megalocytic and dysmorphic neurons may result from somatic mutations of some, but not all, neuronal precursors in the periventricular region. FCD2 and hemimegalencephaly (HME) may have the same pathogenesis, the principal difference being timing of onset within the 33 mitotic cycles of the periventricular neuroepithelium to exponentially produce the total neuronal population of the cerebral cortex: if the mutation occurs during the late mitotic cycles, FCD2 results as a small dysgenesis; if the mutation occurs in the early mitotic cycles, the distribution of abnormal neurons is more extensive and HME may result. Why some cerebral malformations are more epileptogenic than others, despite similar histological features, remains enigmatic but probably involves differences in synaptic circuitry among individual cases.",Alexander disease;article;brain cortex;brain development;brain malformation;cell cycle;cell migration;cortical dysplasia;electron microscopy;epilepsy;gene expression;genetic disorder;human;macroglia;metabolic disorder;microtubule;morphogenesis;nuclear magnetic resonance imaging;pathogenesis;priority journal;synaptogenesis;tauopathy,"Sarnat, H. B.;Flores-Sarnat, L.",2014,,,0,
1464,Reversible leukoencephalopathy in cerebral amyloid angiopathy presenting as subacute dementia,"This report concerns a 71-year-old woman who had rapid progressive dementia along with myocloni and increased blood pressure. Cranial computed tomography and magnetic resonance imaging scans showed bilateral widespread white matter changes with mass effect. A brain biopsy revealed an amyloid angiopathy in leptomeningeal as well as cerebral cortex arteries. After 2 months of antihypertensive treatment, a dramatic improvement of cognitive functions and a spectacular regression of leukoencephalopathy were observed. We suggest that hypertensive encephalopathy may worsen or reveal cerebral amyloid angiopathy.",,"Sarazin, M.;Amarenco, P.;Mikol, J.;Dimitri, D.;Lot, G.;Bousser, M. G.",2002,2002,,0,
1465,Anterior choroidal artery infarction presenting as a progressive cognitive deficit,"Purpose: The authors describe a patient in whom neuroimaging using Tc- 99m HMPAO SPECT, F-18 fluorodeoxyglucose (F-18 FDG) coincidence imaging, and magnetic resonance imaging (MRI) identified an anterior choroidal artery infarction. Neuroimaging played a critical role in confirming this diagnosis, because the patient had symptoms of progressive cognitive decline and satisfied the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease (AD). Methods: Tc-99m HMPAO brain SPECT was performed using a triple-head gamma camera. F-18 FDG scanning was obtained 40 minutes after intravenous injection of 5 mCi F-18 FDG using a coincidence camera. A brain MRI scan was performed using a 1.5-Tesla scanner. Results: Tc-99m HMPAO SPECT showed focal hypoperfusion to the right parahippocampal cortex. F-18 FDG coincidence imaging showed a more extensive reduction in glucose metabolism compared with SPECT. The MRI scan confirmed the presence of a small segmental choroidal artery infarction. The Tc-99m HMPAO and F-18 FDG scans were not consistent with AD. Conclusions: This case illustrates the value of the regional cerebral blood flow SPECT for evaluating memory impairment in the elderly. Decreased regional cerebral blood flow to the posterior temporoparietal region is consistent with AD, whereas regional cerebral blood flow diminution in a vascular territory is consistent with vascular dementia. In this case, the patient was clinically diagnosed with AD, and SPECT was performed to establish the baseline regional cerebral blood flow before the cholinesterase inhibitor donepezil was administered. An infarction was diagnosed on the regional cerebral blood flow brain SPECT scan, which was later confirmed by MRI. Infarctions of the parahippocampal cortex may result in memory impairment, which can appear clinically similar to AD.",,"Sarangi, S.;San Pedro, E. C.;Mountz, J. M.",2000,March,,0,
1466,Optimization of magnetization-prepared 3-dimensional fluid attenuated inversion recovery imaging for lesion detection at 7 T,"PURPOSE: The aim of this study was to optimize the 3-dimensional (3D) fluid attenuated inversion recovery (FLAIR) pulse sequence for isotropic high-spatial-resolution imaging of white matter (WM) and cortical lesions at 7 T. MATERIALS AND METHODS: We added a magnetization-prepared (MP) FLAIR module to a Cube 3D fast spin echo sequence and optimized the refocusing flip angle train using extended phase graph simulations, taking into account image contrast, specific absorption rate (SAR), and signal-to-noise ratio (SNR) as well as T1/T2 values of the different species of interest (WM, grey matter, lesions) at 7 T. We also effected improved preparation homogeneity at 7 T by redesigning the refocusing pulse used in the MP segments. Two sets of refocusing flip angle trains-(a) an SNR-optimal and (b) a contrast-optimal set-were derived and used to scan 7 patients with Alzheimer disease/cognitive impairment and 7 patients with multiple sclerosis. Conventional constant refocusing flip MP-FLAIR images were also acquired for comparison. Lesion SNR, contrast, and lesion count were compared between the 2 optimized and the standard FLAIR sequences. RESULTS: Whole brain coverage with 0.8 mm isotropic spatial resolution in approximately 5-minute scan times was achieved using the optimized 3D FLAIR sequences at clinically acceptable SAR levels. The SNR efficiency of the SNR-optimal sequence was significantly better than that of conventional constant refocusing flip MP-FLAIR sequence, whereas the scan time was reduced more than 2-fold ( approximately 5 vs >10 minutes). The contrast efficiency of the contrast-optimal sequence was comparable with that of the constant refocusing flip sequence. Lesion load ascertained by lesion counting was not significantly different among the sequences. CONCLUSION: Magnetization-prepared FLAIR-Cube with refocusing flip angle trains optimized for SNR and contrast can be used to characterize WM and cortical lesions at 7 T with 0.8 mm isotropic resolution in short scan times and without SAR penalty.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Image Enhancement/ methods;Image Processing, Computer-Assisted/methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Magnetics;Male;Middle Aged;Multiple Sclerosis/ pathology;Prospective Studies;Signal-To-Noise Ratio;White Matter/pathology","Saranathan, M.;Tourdias, T.;Kerr, A. B.;Bernstein, J. D.;Kerchner, G. A.;Han, M. H.;Rutt, B. K.",2014,May,10.1097/rli.0000000000000041,0,
1467,Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging,"Areas of high signal intensity in white matter are identified on brain magnetic resonance (MR) imaging studies in 25%-50% of elderly subjects. The authors used phosphorus-31 MR spectroscopy to characterize the metabolic status of hemispheric white matter brain volumes in 30 elderly subjects with white matter areas of high signal intensity at MR imaging. Compared with white matter volumes with no or minimal areas of high intensity, white matter volumes with extensive areas of high intensity evidenced a 26% decrease in the adenosine triphosphate (ATP)/inorganic phosphate (Pi) ratio (P = .03) and a 21% decrease in the ATP concentration (P = .05), with the Pi level unchanged. A pilot P-31 spectroscopic imaging study in a subject with a large, coalescing white matter area of high signal intensity demonstrated large reductions in metabolite concentrations in the high-signal-intensity area. These results suggest that extensive white matter areas of high signal intensity indicate a process that affects white matter cellular energy metabolism.",Adenosine Triphosphate/metabolism;Aged;Brain/ metabolism;Dementia/metabolism;Humans;Magnetic Resonance Spectroscopy;Phosphates/metabolism;Phosphorus/ metabolism,"Sappey-Marinier, D.;Deicken, R. F.;Fein, G.;Calabrese, G.;Hubesch, B.;Van Dyke, C.;Dillon, W. P.;Davenport, L.;Meyerhoff, D. J.;Weiner, M. W.",1992,Apr,10.1148/radiology.183.1.1549681,0,
1468,MRI and neuropsychological correlates of dementia in Binswanger's disease,"Nuclear magnetic resonance imaging (MRI) has facilitated diagnosis of Binswanger's disease in vivo, which has proven to be a more common disease entity than once believed. These patients generally present with hypertension, progressive dementia, hydrocephalus, gait difficulty, and personality change. A patient is presented with MRI findings of white-matter destruction and subcortical lesions, and with neuropsychological findings of higher-order cognitive impairment but selectively preserved language and visuospatial-perceptual skills. The relationship between the patient's cognitive-behavioral symptoms and the presence of disconnection syndrome is discussed. In addition, the utility of neuropsychological examination is reviewed. Finally, implications for differentiating cortical from subcortical dementia with psychometric test data are discussed.",,"Sapin, L. R.;Frishberg, B. M.;Sherman, J. L.",1990,,,0,
1469,Lymphomatosis cerebri mimicking iatrogenic Creutzfeldt-Jakob disease,"Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL) whereby individual lymphoma cells infiltrate the cerebral white matter without causing a mass effect. The disease characteristically presents as a rapidly progressive dementia, which opens an ample differential diagnosis of toxic, metabolic, neurodegenerative and infective causes. Other presentations also include changes in personality, myoclonus and psychotic symptoms. Here we report a patient who presented with a rapidly progressive dementia with a unique surgical history of a dural mater graft in the 1970s. The diagnosis of iatrogenic Creutzfeldt-Jakob disease (iCJD) was initially considered. However, the patient's clinical status deteriorated rapidly with no response to symptomatic treatment and she died 2 months after symptom onset. A diagnosis of T-type LC was reached at autopsy.",acridine;chlorpromazine;immunoglobulin G;phenothiazine;phenytoin;T lymphocyte receptor;adult;anamnesis;angiolipoma;article;autopsy;case report;codon;cognitive defect;craniopharyngioma;dementia;differential diagnosis;diffusion weighted imaging;disease course;disease severity;disorientation;drug substitution;drug withdrawal;dura mater;erythrocyte sedimentation rate;female;follow up;gene rearrangement;homozygosity;human;hypopituitarism;iatrogenic Creutzfeldt Jakob disease;immunoglobulin blood level;lymphadenopathy;lymphomatosis cerebri;middle aged;myoclonus;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;outcome assessment;primary central nervous system lymphoma;seizure,"Sanz, E. R.;Cabeza, M. Á T.;Portugal, F. S.;García-Bragado, F.",2014,,,0,
1470,Features of patients with nonfluent/agrammatic primary progressive aphasia with underlying progressive supranuclear palsy pathology or corticobasal degeneration,"IMPORTANCE We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy. OBJECTIVE To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included. MAIN OUTCOMES AND MEASURES Clinical, cognitive, and neuroimaging longitudinal datawere analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally. RESULTS Patient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms. CONCLUSIONS AND RELEVANCE In patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imagingmay be useful for differentiating underlying PSP from CBD pathology during life.",adult;age;aged;article;autopsy;clinical article;cognitive defect;controlled study;corticobasal degeneration;dysarthria;dysphagia;eye movement disorder;female;follow up;handedness;human;longitudinal study;male;memory disorder;neuroimaging;neurologic disease;nuclear magnetic resonance imaging;prefrontal cortex;primary progressive aphasia;priority journal;progressive nonfluent aphasia;progressive supranuclear palsy;prospective study;sex;speech disorder;white matter lesion;working memory,"Santos-Santos, M. A.;Mandelli, M. L.;Binney, R. J.;Ogar, J.;Wilson, S. M.;Henry, M. L.;Hubbard, H. I.;Meese, M.;Attygalle, S.;Rosenberg, L.;Pakvasa, M.;Trojanowski, J. Q.;Grinberg, L. T.;Rosen, H.;Boxer, A. L.;Miller, B. L.;Seeley, W. W.;Gorno-Tempini, M. L.",2016,,,0,
1471,Diffusion tensor tractography versus volumetric imaging in the diagnosis of behavioral variant frontotemporal dementia,"MRI diffusion tensor imaging (DTI) studies of white matter integrity in behavioral variant frontotemporal dementia have consistently shown involvement of frontal and temporal white matter, corresponding to regional loss of cortical volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and thus we wanted to explore if DTI is a better method to discriminate patients and controls than volumetric imaging. We examined the anterior cingulum bundle in 14 patients with behavioral variant frontotemporal dementia and 22 healthy controls using deterministic manual diffusion tensor tractography, and compared DTI parameters with two measures of cortical atrophy, VBM and cortical thickness, of the anterior cingulate cortex (ACC). Statistically significant changes between patients and controls were detected in all DTI parameters, with large effect sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to 0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC. Results from the AUC were confirmed with binary logistic regression analysis including demographic variables, but only for fractional anisotropy and mean diffusivity. Ability to classify patient/nonpatient status was significantly better for mean diffusivity vs. VBM (p=0.031), and borderline significant for fractional anisotropy vs. VBM (p=0.062). The results indicate that DTI could offer advantages in comparison with the assessment of cortical volume in differentiating patients with behavioral variant frontotemporal dementia and controls.","Aged;Aged, 80 and over;Cone-Beam Computed Tomography/methods;Diffusion Tensor Imaging/ methods;Female;Frontotemporal Dementia/ diagnosis;Gyrus Cinguli/ anatomy & histology;Humans;Male;Middle Aged;Statistics, Nonparametric","Santillo, A. F.;Martensson, J.;Lindberg, O.;Nilsson, M.;Manzouri, A.;Landqvist Waldo, M.;van Westen, D.;Wahlund, L. O.;Latt, J.;Nilsson, C.",2013,,10.1371/journal.pone.0066932,0,
1472,Grey and White Matter Clinico-Anatomical Correlates of Disinhibition in Neurodegenerative Disease,"Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the ""prefrontal"" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.",,"Santillo, A. F.;Lundblad, K.;Nilsson, M.;Landqvist Waldo, M.;van Westen, D.;Latt, J.;Blennow Nordstrom, E.;Vestberg, S.;Lindberg, O.;Nilsson, C.",2016,,,0,
1473,In vivo imaging of astrocytosis in Alzheimer's disease: an (1)(1)C-L-deuteriodeprenyl and PIB PET study,"PURPOSE: Astrocytosis is an important feature of the neuropathology of Alzheimer's disease (AD), yet there is currently no way of detecting this phenomenon in vivo. METHODS: In this study we examine the retention of the positron emission tomography (PET) tracer (11)C-L-deuteriodeprenyl (DED), thought to bind activated astrocytes, in 9 patients with moderate to severe AD compared with 11 healthy controls. As a measure of amyloid load, (11)C-labelled Pittsburgh Compound B (PIB) retention was determined. RESULTS: Results show a significantly higher (11)C-L-DED retention in the frontal (35.1% increase, p = 0.001), parietal (35.2%, p = 0.001), temporal (30.9%, p = 0.0001) and medial temporal lobes (22.3%, p = 0.001) in AD compared to healthy controls after blood flow correction. DED retention in the sensorimotor and occipital cortices, and in white matter and subcortical structures, did not differ between groups. There was a moderate but statistically significant (r = 0.492, p = 0.01) correlation between DED and PIB retention values. CONCLUSION: Our conclusion is that DED may serve as an in vivo marker for astrocytosis in AD, providing a window into intermediate processes between amyloidosis and neuronal loss and a means of monitoring immunotherapy.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ metabolism/radionuclide imaging;Aniline Compounds/ pharmacokinetics;Brain/ metabolism/radionuclide imaging;Carbon Radioisotopes;Deuterium;Female;Gliosis/complications/ metabolism/radionuclide imaging;Humans;Positron-Emission Tomography/ methods;Radiopharmaceuticals/metabolism/pharmacokinetics;Selegiline/ pharmacokinetics;Thiazoles/ pharmacokinetics;Tissue Distribution","Santillo, A. F.;Gambini, J. P.;Lannfelt, L.;Langstrom, B.;Ulla-Marja, L.;Kilander, L.;Engler, H.",2011,Dec,10.1007/s00259-011-1895-9,0,
1474,White Matter Microstructural Integrity Is Associated with Executive Function and Processing Speed in Older Adults with Coronary Artery Disease,"OBJECTIVE: Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. Although cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study was to determine if WM microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD. METHODS: Forty-nine CAD patients (66 +/- 7 years old, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal-appearing WM was quantified as fractional anisotropy (FA) using DTI in nine bilateral and two interhemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%. RESULTS: Executive function was most significantly associated with FA in the left parahippocampal cingulum (beta = 0.471, t = 3.381, df = 44, p = 0.002) and left inferior fronto-occipital fasciculus (beta = 0.430, t = 2.984, df = 44, p = 0.005). FA was not associated with memory in any of the WM tracts examined. CONCLUSION: These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia.","Aged;Aged, 80 and over;Anisotropy;Canada;Cognition/ physiology;Coronary Artery Disease/ physiopathology/psychology;Cross-Sectional Studies;Diffusion Tensor Imaging;Executive Function/ physiology;Female;Humans;Imaging, Three-Dimensional;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;White Matter/ ultrastructure","Santiago, C.;Herrmann, N.;Swardfager, W.;Saleem, M.;Oh, P. I.;Black, S. E.;Lanctot, K. L.",2015,Jul,10.1016/j.jagp.2014.09.008,0,
1475,RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder,"OBJECTIVE: To identify the genetic cause in 2 Belgian families with autosomal recessive Huntington-like disorder (HDL). METHODS: Homozygosity mapping and whole-exome sequencing in a consanguineous family as well as Sanger sequencing of the candidate gene in an independent family with HDL followed by genotype-phenotype correlation studies. RESULTS: We identified a homozygous mutation in the gene RNF216 p.(Gly456Glu) within a shared 4.8-Mb homozygous region at 7p22.3 in 2 affected siblings of a consanguineous HDL family. In an independent family, 2 siblings with HDL were compound heterozygous for mutations in RNF216 p.(Gln302*) and p.(Tyr539Cys). Chorea, behavioral problems, and severe dementia were the core clinical signs in all patients. Brain imaging consistently showed white matter lesions. Low gonadotropin serum levels and cerebellar atrophy could be demonstrated in the index family. CONCLUSIONS: Mutations in RNF216 have recently been found in families with Gordon Holmes syndrome, a condition defined by hypogonadotropic hypogonadism and cerebellar ataxia. The mode of inheritance was proposed to be oligogenic for most families. We describe novel RNF216 mutations causing an HDL phenotype with pure monogenic recessive inheritance. Subclinical serum evidence of hypogonadotropic hypogonadism links this disorder to Gordon Holmes syndrome. Our study thus challenges the oligogenic inheritance model and emphasizes chorea as an essential clinical feature in RNF216-mediated neurodegeneration.","Adult;Age of Onset;Aged;Belgium;Cerebellum/pathology;Consanguinity;Female;Genes, Recessive;Gonadotropins/blood;Humans;Huntington Disease/blood/ genetics/pathology;Male;Middle Aged;Multifactorial Inheritance;Mutation;Pedigree;Ubiquitin-Protein Ligases/ genetics","Santens, P.;Van Damme, T.;Steyaert, W.;Willaert, A.;Sablonniere, B.;De Paepe, A.;Coucke, P. J.;Dermaut, B.",2015,Apr 28,10.1212/wnl.0000000000001521,0,
1476,"MRI of the brain, EEG sleep spindles and SPECT in the early diagnosis of infantile neuronal ceroid lipofuscinosis","Two patients with infantile neuronal ceroid lipofuscinosis are presented whose clinical diagnosis was based on the typical clinical picture, together with absent sleep spindles and MRI findings (hypointense thalami and hyperintense periventricular white matter) as early as 18 months in one girl. In addition to a flat cortical SEP, these abnormalities appeared earlier than the typical ERG and VEP findings used previously for clinical diagnosis of this condition. MRI of the other patient showed the same changes and EEG sleep spindles were absent by two years.",baclofen;levomepromazine;article;brain;case report;early diagnosis;electroencephalogram;electroretinogram;evoked visual response;female;human;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;preschool child;priority journal;single photon emission computer tomography;sleep spindle,"Santavuori, P.;Raininko, R.;Vanhanen, S. L.;Launes, J.;Sainio, K.",1992,,,0,
1477,Progressive Multifocal Leukoencephalopathy with Balanced CD4/CD8 T-Cell Infiltration and Good Response to Mefloquine Treatment,"A 53-year-old man was admitted for sub-acute progressive dementia and Gerstmann syndrome. MRI demonstrated lesions in the white matter involving the left parietal lobe, accompanied by speckled or faint linear peripheral enhancement. Brain biopsy revealed JC virus infection in oligodendrocytes and balanced infiltration of CD8+ and CD4+ T lymphocytes. We diagnosed progressive multifocal leukoencephalopathy (PML) with controlled inflammation. The finding of CD4/CD8 T cells in the infected PML brain suggested therapeutically valuable immune system involvement, which we decided to preserve by withholding corticosteroids. We treated the patient with risperidone, cytarabine and mefloquine to suppress virus replication, but not with the corticosteroid that is conventionally used in inflammatory PML cases. The patient was discharged three months after admission, and one year later, his score on the Mini-Mental State Examination had recovered to 26/30, from 5/30 on admission.",,"Sanjo, N.;Kina, S.;Shishido-Hara, Y.;Nose, Y.;Ishibashi, S.;Fukuda, T.;Maehara, T.;Eishi, Y.;Mizusawa, H.;Yokota, T.",2016,,10.2169/internalmedicine.55.6051,0,
1478,Diffusion-weighted magnetic resonance imaging in Alzheimer's disease,"Diffusion-weighted imaging (DWI) is a powerful new magnetic resonance imaging technique for evaluating tissue pathophysiology in vivo. We performed DWI in three orthogonal spatial directions in 10 patients with mild to moderate Alzheimer's disease (AD) and 11 control subjects. Average apparent diffusion coefficients (ADCavg) were calculated for gray matter regions, and anisotropy indexes were calculated for white matter regions. Global measures of atrophy and white matter hyperintensities (WMH) were obtained on T2-weighted images to control for their potential confounding effects on ADCavg and anisotropy. The measures of atrophy and WMH differed between the groups and were used as covariates in the subsequent statistical analyses. Patients with AD demonstrated diminished anisotropy in the posterior white matter (p < 0.0001) and increased ADCavg in the hippocampus (p < 0.05) when compared to the control group. Diffusion measures did not correlate with the severity of dementia. DWI provides a unique, quantitative parameter that may be sensitive to the pathophysiological and/or microstructural abnormalities that occur in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Atrophy;Brain/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales","Sandson, T. A.;Felician, O.;Edelman, R. R.;Warach, S.",1999,Mar-Apr,17099,0,
1479,Autosomal dominant leukodystrophy presenting as Alzheimer's-type dementia,"Autosomal dominant leukodystrophy is a neurodegenerative disorder caused by either point mutations or duplication of the lamin B1 gene on chromosome 5q23. The typical clinical picture consists of autonomic symptoms as well as cerebellar and pyramidal signs. Here we present the case of a 57-year-old female referred to our clinic due to cognitive decline. Neurological examination was significant for cognitive impairment as well as pyramidal and cerebellar signs. Brain MRI displayed diffuse hyperintense lesions in the subcortical white matter, pontine nuclei, brachium pontis and restiform body. The diagnosis was confirmed via genetic testing. Autosomal dominant leukodystrophy should be included in the differential diagnosis of patients presenting with cognitive impairment, motor signs, and leukodystrophy-like images.",Alzheimer's disease;Autosomal dominant leukodystrophy;Cerebellar syndrome;Demyelinating disease;Lamin B1;Pyramidal syndrome,"Sandoval-Rodriguez, V.;Cansino-Torres, M. A.;Saenz-Farret, M.;Castaneda-Cisneros, G.;Moreno, G.;Zuniga-Ramirez, C.",2017,Oct,,0,
1480,Incidental Findings on Brain MR Imaging in Older Community-Dwelling Subjects Are Common but Serious Medical Consequences Are Rare: A Cohort Study,"Objectives:Incidental findings in neuroimaging occur in 3% of volunteers. Most data come from young subjects. Data on their occurrence in older subjects and their medical, lifestyle and financial consequences are lacking. We determined the prevalence and medical consequences of incidental findings found in community-dwelling older subjects on brain magnetic resonance imaging.Design:Prospective cohort observational study.Setting:Single centre study with input from secondary care.Participants:Lothian Birth Cohort 1936, a study of cognitive ageing.Main Outcome Measures:Incidental findings identified by two consultant neuroradiologists on structural brain magnetic resonance imaging at age 73 years; resulting medical referrals and interventions.Primary and Secondary Outcome Measures:Prevalence of incidental findings by individual categories: neoplasms, cysts, vascular lesions, developmental, ear, nose or throat anomalies, by intra- and extracranial location; visual rating of white matter hyperintensities and brain atrophy.Results:There were 281 incidental findings in 223 (32%) of 700 subjects, including 14 intra- or extracranial neoplasms (2%), 15 intracranial vascular anomalies (2%), and 137 infarcts or haemorrhages (20%). Additionally, 153 had moderate/severe deep white matter hyperintensities (22%) and 176 had cerebral atrophy at, or above, the upper limit of normal (25%) compared with a normative population template. The incidental findings were unrelated to white matter hyperintensities or atrophy; about a third of subjects had both incidental findings and moderate or severe WMH and a quarter had incidental findings and atrophy. The incidental findings resulted in one urgent and nine non-urgent referrals for further medical assessment, but ultimately in no new treatments.Conclusions:In community-dwelling older subjects, incidental findings, including white matter hyperintensities and atrophy, were common. However, many findings were not of medical importance and, in this age group, most did not result in further assessment and none in change of treatment. © 2013 Sandeman et al.",,"Sandeman, E. M.;Hernandez, M. C. V.;Morris, Z.;Bastin, M. E.;Murray, C.;Gow, A. J.;Corley, J.;Henderson, R.;Deary, I. J.;Starr, J. M.;Wardlaw, J. M.",2013,,,0,
1481,Selected saliency based analysis for the diagnosis of Alzheimer's disease using structural magnetic resonance image,"Alzheimer's disease is the most common type of dementia. This paper presents a novel computer-aided diagnosis (CAD) tool for the diagnosis of the Alzheimer's disease (AD) using structural Magnetic Resonance Images (MRIs). The proposed work applies saliency based mapping for segmented MRI brain image and selects the most distinguished regions using FDR method for classification. The method could exactly spot the AD affected regions in the MRI images which could assist the medical experts for treatment. After multiscale decomposition, Brain images are segmented into Cerebrospinal fluid (CSF), white matter and gray matter using (EM/MPM) algorithm. Orientation features are extracted using Gabor filter bank at various scales of segmented brain image after which Salient regions are extracted using Graph Based Visual Saliency (GBVS) method. Using Fisher Discriminant Ratio method (FDR), the most discriminant salient regions are retained in the saliency volumes. Kernel matrices are constructed using Histogram Intersection for all the saliency volumes and weights are measured using GMKL algorithm with libSVM as classifier. From the results two fold advantages are inferred, first the method could spot the exact affected region, second reduces the number of voxels, storage space and hence reduces the overall simulation time to approximately 50%. The maximum classification result of 97% accuracy, 92% sensitivity, 98% specificity and 95.91% balanced accuracy across a group of 126 subjects (28 AD and 98 normal subjects) from 60 to 96 years of age group had been obtained.",,"Sandanalakshmi, R.;Sardius, V.",2016,1,,0,
1482,MM1 variant of sporadic Creutzfeldt-Jakob disease with long duration akinetic mutism state,"INTRODUCTION: When patients present with a characteristic clinical picture of Creutzfeldt-Jakob disease (CJD) associated with positive 14-3-3 assay, periodic sharp wave complexes, high-signal of the striatum on magnetic resonance imaging, and homozygosis methionine (M) in codon 129, the median survival is 4 to 6 months. CLINICAL CASE: We report a 58-year-old woman with these typical features who survived 21 months, 19 of them in an akinetic mutism state. The autopsy confirmed the diagnosis of the most common CJD phenotype (MM1), usually associated with a shorter survival, and demyleinitation of the white matter (panencephalopathic form). CONCLUSIONS: The MM1 variant of CJD, with a rapidly progressive course leading into an akinetic mutism shortly after disease onset can be followed by a long akinetic mutism state. This profile is suggestive of panencephalopathic form and should be taken into account when counselling about survival.",,"Sanchez-Valle, R.;Santamaria, J.;Rey, M. J.;Rodriguez, A.;Graus, F.;Saiz, A.",2006,Oct,,0,
1483,White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease,"PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p < 0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p < 0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.",,"Sanchez-Valle, R.;Monte, G. C.;Sala-Llonch, R.;Bosch, B.;Fortea, J.;Llado, A.;Antonell, A.;Balasa, M.;Bargallo, N.;Molinuevo, J. L.",2016,Feb 20,10.3233/jad-150899,0,
1484,Cerebral Amyloid Angiopathy-Related Microbleeds Correlate with Glucose Metabolism and Brain Volume in Alzheimer's Disease,"BACKGROUND: Microbleeds (MBs) are frequently observed in Alzheimer's disease (AD); however, the relevance to AD pathophysiology has not been elucidated. OBJECTIVES: We investigated correlation of MBs, especially cerebral amyloid angiopathy (CAA)-related MBs with cognitive function, gray matter volume, and glucose metabolism in AD. METHODS: We performed magnetic resonance imaging including T2*-weighted imaging sequence for 206 patients with AD. Among them, 158 AD patients with no focal brain lesions except for MBs were investigated with cognitive tests, voxel-based morphometry, and 18F-fluorodeoxyglucose positron emission tomography in a cross-sectional observational study. RESULTS: Of the 158 patients with no hemorrhagic and/or ischemic stroke lesions except for MBs, 27 patients had MBs, in which 17 patients showed CAA-related MBs that located only in cortex/subcortex (CAA-related MBs), and 10 patients showed CAA-unrelated MBs that located in deep regions regardless of the presence of MBs in cortical/subcortical regions. There were slightly but significant differences in cognitive functions between the patients without MBs, those with CAA-related MBs, and those with CAA-unrelated MBs. MBs were recognized frequently in the occipital lobe in the patients with CAA-related MBs. The patients with CAA-related MBs showed gray matter atrophy in the temporal lobe and cerebellum, and glucose hypometabolism in the temporal lobe compared with those without MBs. CONCLUSIONS: Our results indicate that MBs, particularly CAA-related MBs would cause gray matter atrophy and glucose hypometabolism in AD.",,"Samuraki, M.;Matsunari, I.;Yoshita, M.;Shima, K.;Noguchi-Shinohara, M.;Hamaguchi, T.;Ono, K.;Yamada, M.",2015,,10.3233/jad-150274,0,
1485,CADASIL: MRI may be normal in the fourth decade of life - A case report,"Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests by migraine with aura, cerebral ischemic events, mood disturbances and dementia. Brain MRI lesions typically precede the symptoms from 10 to 15 years and previous evidence showed all CADASIL patients above 35 years old have an abnormal MRI, supporting the clinical diagnosis. Case results We present a 37-year-old female patient with migraine without aura, a family history of CADASIL, normal brain 3-Tesla MRI and normal skin biopsy, even though a pathogenic NOTCH3 gene mutation (allele 2, exon 11, c.1672 C\gtT, p.Arg558Cys) was detected. Conclusions When CADASIL is strongly suspected, a normal brain MRI, even in the fourth decade of life, does not rule out the diagnosis and should not discourage the genetic test.",acetylsalicylic acid;analgesic agent;cytosine;Notch3 receptor;thymine;adult;amnesia;article;CADASIL;case report;Caucasian;cerebrovascular accident;exon;family history;female;gene mutation;headache;human;human tissue;migraine;migraine aura;neurologic disease;NOTCH3 gene;nuclear magnetic resonance imaging;skin biopsy,"Samões, R.;Alves, J. E.;Taipa, R.;Silva, J.;Melo Pires, M.;Pereira-Monteiro, J. M.",2016,,10.1177/0333102415618613,0,
1486,CADASIL: MRI may be normal in the fourth decade of life - a case report,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests by migraine with aura, cerebral ischemic events, mood disturbances and dementia. Brain MRI lesions typically precede the symptoms from 10 to 15 years and previous evidence showed all CADASIL patients above 35 years old have an abnormal MRI, supporting the clinical diagnosis. CASE RESULTS: We present a 37-year-old female patient with migraine without aura, a family history of CADASIL, normal brain 3-Tesla MRI and normal skin biopsy, even though a pathogenic NOTCH3 gene mutation (allele 2, exon 11, c.1672 C\gtT, p.Arg558Cys) was detected. CONCLUSIONS: When CADASIL is strongly suspected, a normal brain MRI, even in the fourth decade of life, does not rule out the diagnosis and should not discourage the genetic test.",,"Samoes, R.;Alves, J. E.;Taipa, R.;Silva, J.;Melo Pires, M.;Pereira-Monteiro, J. M.",2015,Dec 7,10.1177/0333102415618613,0,
1487,"Vanishing white matter disease: An Italian case with A638G mutation in exon 5 of EIF2B2 gene, an unusual early onset and a long course","We report the clinical description of an Italian patient with c.638A>G mutation in exon 5 of EIF2B2 gene and a very slow progressive Vanishing White Matter disease phenotype. Infact, in relation to her causative mutation, our patient had an unusual early onset and long course. Furthermore, other than standard MRI examination and spectroscopy study, we report DWI and ADC maps and FA maps reconstruction from DTI in order to describe brain tissue degeneration in vanishing white matter disease. © 2012 Springer-Verlag.",adenosine;guanidine;adult;amino acid substitution;anamnesis;apathy;article;Babinski reflex;brain mapping;case report;cerebellar ataxia;daily life activity;developmental disorder;diffusion coefficient;diffusion weighted imaging;disease course;dysarthria;educational status;EIF2B2 gene;exon;female;gene;gene identification;gene location;gene mutation;homozygosity;human;hypergonadotropic hypogonadism;hyporeflexia;image reconstruction;menarche;menstrual irregularity;mental deterioration;Mini Mental State Examination;neuroimaging;onset age;pollakisuria;proton nuclear magnetic resonance;quadriplegia;secondary amenorrhea;spastic paresis;speech rate;tendon reflex;urine incontinence;vanishing white matter disease;walking difficulty;Wechsler intelligence scale;white matter lesion,"Sambati, L.;Agati, R.;Bacci, A.;Bianchi, S.;Capellari, S.",2013,,,0,
1488,Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan,"We describe 2 normotensive sisters presenting slowly progressive dementia associated with acute or subacute focal neurological symptoms, unilateral or bilateral motor signs, and dysarthria. Their father, who died in the seventh decade, had a similar clinical picture. Computerized axial tomography (CT) scan of the head showed symmetrical hypodensities in the periventricular white matter and mild to moderate hydrocephalus. In these patients a diagnosis of Binswanger's disease was based on the clinical features supported by white matter changes on CT scan. Our study suggests that genetic factors may play a role in the etiology of Binswanger's disease.",adult;article;brain;case report;cerebrovascular disease;computer assisted tomography;female;genetics;human;male;middle aged;multiinfarct dementia;nuclear magnetic resonance imaging;pathology;pedigree;psychological aspect;radiography;recurrent disease;syndrome,"Salvi, F.;Michelucci, R.;Plasmati, R.;Parmeggiani, L.;Zonari, P.;Mascalchi, M.;Tassinari, C. A.",1992,,,0,
1489,Angiography-negative primary central nervous system vasculitis: A syndrome involving small cerebral vessels,"Primary central nervous system vasculitis (PCNSV) is a rare and poorly understood syndrome. We describe the clinical findings in 8 patients who appear to have a distinct subset of PCNSV. We identified 101 consecutive patients with PCNSV who were seen between January 1, 1983, and December 31, 2003. The diagnosis was based on conventional angiography in 70 patients and on central nervous system biopsy in 31 patients. Six of the 31 patients also had angiograms showing changes of vasculitis. Thus, 76 patients of the cohort had abnormal angiograms. Eight of the 101 patients had normal angiograms (""angiography- negative"") but had brain biopsies that showed vasculitis. We compared the clinical and laboratory findings and outcomes of the 8 patients with angiography-negative PCNSV with those of the 76 patients with PCNSV whose angiograms showed evidence of vasculitis (""angiography-positive""). In comparison with the 76 patients with angiography-positive PCNSV, the 8 patients with angiography-negative PCNSV more commonly had 1) a cognitive disorder (87.5% vs. 43.4%; p =.024); 2) cerebrospinal fluid abnormalities (a protein level ≥700 mg/L or a white blood cell count ≥10 × 10/L) (100% vs. 35.5%; p =.034); and 3) meningeal or parenchymal enhancing lesions on magnetic resonance imaging (75.0% vs. 23.9%; p =.007). Other differences between the 2 groups were observed but were not significantly different. All patients with angiography-negative PCNSV responded to treatment and none died. Angiography-negative PCNSV appears to be a distinct subtype of cerebral vasculitis with small vessel involvement beyond the resolution of conventional angiography and is associated with a favorable outcome. Copyright © 2008 by Lippincott Williams & Wilkins.",,"Salvarani, C.;Brown, R. D.;Calamia, K. T.;Christianson, T. J. H.;Huston, J.;Meschia, J. F.;Giannini, C.;Miller, D. V.;Hunder, G. G.",2008,September,,0,
1490,Operationalizing mild cognitive impairment criteria in small vessel disease: the VMCI-Tuscany Study,"INTRODUCTION: Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile. METHODS: In a sample of cerebral small vessel disease (SVD) patients, we assessed MCI subtypes distributions according to different operationalization of Winblad criteria and compared the neuroimaging features of single versus multidomain MCI. We applied three MCI diagnostic scenarios in which the cutoffs for objective impairment and the number of considered neuropsychological tests varied. RESULTS: Passing from a liberal to more conservative diagnostic scenarios, of 153 patients, 5% were no longer classified as MCI, amnestic multidomain frequency decreased, and nonamnestic single domain increased. Considering neuroimaging features, severe medial temporal lobe atrophy was more frequent in multidomain compared with single domain. DISCUSSION: Operationalizing MCI criteria changes the relative frequency of MCI subtypes. Nonamnestic single domain MCI may be a previously nonrecognized type of MCI associated with SVD.",Aged;Atrophy;Cerebrovascular Disorders/ diagnosis;Cognitive Dysfunction/ diagnosis;Disease Progression;Female;Humans;Italy;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prodromal Symptoms;Prospective Studies;Temporal Lobe/diagnostic imaging;White Matter/diagnostic imaging;Cerebrovascular disease;Cognitive aging;Mild cognitive impairment;Neuropsychology;Vascular dementia,"Salvadori, E.;Poggesi, A.;Valenti, R.;Pracucci, G.;Pescini, F.;Pasi, M.;Nannucci, S.;Marini, S.;Del Bene, A.;Ciolli, L.;Ginestroni, A.;Diciotti, S.;Orlandi, G.;Di Donato, I.;De Stefano, N.;Cosottini, M.;Chiti, A.;Federico, A.;Dotti, M. T.;Bonuccelli, U.;Inzitari, D.;Pantoni, L.;Group, V. MCI-Tuscany Study",2016,Apr,,0,
1491,"The rehabilitation of attention in patients with mild cognitive impairment and brain subcortical vascular changes using the Attention Process Training-II. The RehAtt Study: rationale, design and methodology","Cerebral small vessel disease (SVD) may cause attentional and executive cognitive deficits. No drug is currently available to improve cognitive performance or to prevent dementia in SVD patients, and cognitive rehabilitation could be a promising approach. We aimed to investigate: (1) the effectiveness of the Attention Process Training-II program in the rehabilitation of patients with mild cognitive impairment (MCI) and SVD; (2) the impact of the induced cognitive improvement on functionality and quality of life; (3) the effect of training on brain activity at rest and the possibility of a training-induced plasticity effect. The RehAtt study is designed as a 3-year prospective, single-blinded, randomized clinical trial. Inclusion criteria were: (1) MCI defined according to Winblad et al. criteria; (2) evidence of impairment across attention neuropsychological tests; (3) evidence on MRI of moderate/severe white matter hyperintensities. All enrolled patients are evaluated at baseline, and after 6 and 12 months, according to an extensive clinical, functional, MRI and neuropsychological protocol. The baseline RehAtt cohort includes 44 patients (66 % males, mean +/- SD age and years of education 75.3 +/- 6.8 and 8.3 +/- 4.3, respectively). After baseline assessment, patients have been randomly assigned to 'attention training' or 'standard care'. Treatments and follow-up visits at 6 months are completed, while follow-up visits at 12 months are ongoing. This study is the first attempt to reduce attention deficits in patients affected by MCI with SVD. The results of this pilot experience will represent an essential background for designing larger multicenter, prospective, double-blinded, randomized and controlled clinical trials. TRIAL REGISTRATION: NCT02033850 (ClinicalTrials.gov Identifier).",Attention training;Cerebrovascular diseases;Cognitive rehabilitation;Mild cognitive impairment;Small vessel disease;Vascular dementia,"Salvadori, E.;Poggesi, A.;Valenti, R.;Della Rocca, E.;Diciotti, S.;Mascalchi, M.;Inzitari, D.;Pantoni, L.",2016,Oct,10.1007/s10072-016-2649-z,0,
1492,Early thalamic and cortical hypometabolism in adult-onset dementia due to metachromatic leukodystrophy,"A case of early-onset adult dementia with family history of dementia is reported, characterised by neuropsychological deficits, suggesting frontal involvement, with mild non specific white matter abnormalities on CT scan. Familial Alzheimer's disease was suspected but the neuropathological diagnosis on brain biopsy was metachromatic leukodystrophy. 18FDG-PET revealed a very peculiar pattern of metabolic impairment in thalamic areas, in medial and frontopolar regions, and in occipital lobes. Neuropsychological follow-up showed relatively stable difficulties of long-term memory and signs of frontal lobe dysfunction, similar to those observed in subcortical dementias. MRI subsequently showed periventricular leukoencephalopathy. The brain metabolic pattern observed in that case of metachromatic leukodystrophy was quite different from that reported in other types of dementia.",glucose;adult;Alzheimer disease;article;brain cortex;case report;computer assisted emission tomography;dementia;differential diagnosis;energy metabolism;female;frontal lobe;human;metabolism;metachromatic leukodystrophy;nuclear magnetic resonance imaging;onset age;pathology;scintiscanning;thalamus,"Salmon, E.;Van der Linden, M.;Maerfens Noordhout, A.;Brucher, J. M.;Mouchette, R.;Waltregny, A.;Degueldre, C.;Franck, G.",1999,,,0,
1493,Neuronal fiber bundle lengths in healthy adult carriers of the ApoE4 allele: a quantitative tractography DTI study,"The epsilon 4 (e4) isoform of apolipoprotein E (ApoE) is a known genetic risk factor for suboptimal brain health. Morphometry studies of brains with Alzheimer's disease have reported significant alterations in temporal lobe brain structure of e4 carriers, yet it remains unclear if the presence of an e4 allele is associated with alterations in the microstructure of white matter fiber bundles in healthy populations. The present study used quantitative tractography based on diffusion tensor imaging (qtDTI) to examine the influence of the e4 allele on temporal lobe fiber bundle lengths (FBLs) in 64 healthy older adults with at least one e4 allele (carriers, N = 23) versus no e4 allele (non-carriers, N = 41). Subtests from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were also analyzed to examine memory performance between groups. Analyses revealed shorter FBLs in the left uncinate fasciculus (UF) (p = .038) of e4 carriers compared to non-carriers. By contrast, neither FBLs specific to the temporal lobe nor memory performances differed significantly between groups. Increased age correlated significantly with shorter FBL in the temporal lobe and UF, and with decreased performance on tests of memory. This is the first study to utilize qtDTI to examine relationships between FBL and ApoE genotype. Results suggest that FBL in the UF is influenced by the presence of an ApoE e4 allele (ApoE4) in healthy older adults. Temporal lobe FBLs, however, are more vulnerable to aging than the presence of an e4 allele.","Aged;Aged, 80 and over;Apolipoprotein E4/ genetics;Diffusion Tensor Imaging/ methods;Female;Heterozygote;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ physiology/ ultrastructure;Reference Values;Reproducibility of Results;Sensitivity and Specificity","Salminen, L. E.;Schofield, P. R.;Lane, E. M.;Heaps, J. M.;Pierce, K. D.;Cabeen, R.;Laidlaw, D. H.;Akbudak, E.;Conturo, T. E.;Correia, S.;Paul, R. H.",2013,Sep,10.1007/s11682-013-9225-4,0,
1494,Cilostazol in the management of atherosclerosis,"The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combi- nation of aspirin plus dipyridamole are widely used for primary (in high-risk patients) and secondary prevention of athero- sclerotic diseases. Research of new pharmacological strategies is driven by the need to reduce the risk of bleeding associ- ated with the use of antiplatelet drugs. In this context cilostazol, a type III phosphodiesterase inhibitor, has demonstrated antiplatelet and vasodilator effects with low rate of bleeding complications. This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases. © 2010 Bentham Science Publishers Ltd.",acetylsalicylic acid;adenosine;anticoagulant agent;atenolol;C reactive protein;caspase;cilostazol;clopidogrel;cyclic AMP;dipyridamole;high density lipoprotein cholesterol;interleukin 1beta;low density lipoprotein cholesterol;monocyte chemotactic protein 1;nifedipine;p21 activated kinase;pentoxifylline;phosphodiesterase inhibitor;placebo;protein Bax;protein p53;ticlopidine;tumor necrosis factor alpha;vascular cell adhesion molecule 1;von Willebrand factor;apoptosis;artery disease;artery occlusion;article;atherosclerosis;bleeding;brain blood flow;brain hemorrhage;brain infarction;brain ischemia;calcium cell level;cardiovascular risk;cause of death;cell activation;cell proliferation;cholesterol blood level;smoking;clinical practice;congestive heart failure;coronary artery bypass graft;coronary artery disease;coronary stent;dementia;diabetes mellitus;diarrhea;drug activity;drug indication;drug mechanism;drug safety;endothelium cell;endothelium injury;enzyme activation;feces;follow up;headache;heart infarction;heart muscle revascularization;heart palpitation;heart protection;high risk patient;hospitalization;human;hyperhomocysteinemia;hyperlipidemia;hypertension;inflammation;intermittent claudication;middle cerebral artery;neuroprotection;nuclear magnetic resonance imaging;oxidative stress;percutaneous coronary intervention;peripheral edema;pulse rate;restenosis;risk assessment;risk benefit analysis;risk management;risk reduction;secondary prevention;side effect;smooth muscle fiber;subarachnoid hemorrhage;thrombocyte activation;thrombocyte aggregation;transluminal coronary angioplasty;treatment contraindication;upregulation;vasodilatation;aspirin,"Sallustio, F.;Rotondo, F.;Legge, S. D.;Stanzione, P.",2010,,,0,
1495,MRI and neuropsychological differences in early- and late-life-onset geriatric depression,"We sought to determine whether geriatric patients with late-life-onset major depression have more subcortical hyperintensities on MRI and greater cognitive impairment than age-matched geriatric patients with early-life-onset major depression, suggesting that subcortical disease may be etiologic in late-life depression. Most negative studies of the clinical significance of subcortical hyperintensities on MRI in geriatric patients have sampled from a restricted range of subjects, have employed limited batteries of neuropsychological tests, or have not quantified MRI changes; the present study attempted to address these limitations. Thirty subjects from a geriatric psychiatry inpatient service who were over 60 years of age and presented with major depression were divided into groups with onset of first depression after age 60 (mean = 72.4 years, 15 women, 0 men), and onset of first depression before age 60 (mean = 35.8 years, 12 women, 3 men). Quantitative analysis of MRI yielded the volume of: periventricular hyperintensities (PVH) and deep white-matter hyperintensities (DWMH). Subjects were administered a neuropsychological battery and measures of depression by raters blind to age of onset. The late-onset group had significantly more PVH and DWMH. They were also more impaired on executive and verbal and nonverbal memory tasks. Discriminant analysis using the severity or subcortical signal hyperintensities on MRI, cognitive index, and depression scores correctly predicted late versus early onset of depression in 87% of the early-onset group and 80% of the late-onset group. These findings suggest that late-life-onset depression may be associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance.","Adult;Age of Onset;Aged;Brain/*pathology;Cerebral Ventricles/pathology;Cognition Disorders/complications/epidemiology/pathology;Dementia, Vascular/complications/epidemiology/pathology;Depressive Disorder/classification/*epidemiology/pathology/psychology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Subarachnoid Space/pathology","Salloway, S.;Malloy, P.;Kohn, R.;Gillard, E.;Duffy, J.;Rogg, J.;Tung, G.;Richardson, E.;Thomas, C.;Westlake, R.",1996,Jun,,0,
1496,Vascular Pathology Causing Late Onset Generalized Chorea: A Clinico-Pathological Case Report,"Background: Chorea may occur as a manifestation of an acute stroke. Patients with vascular-related chorea typically present with an acute or subacute onset of hemichorea, contralateral to the lesion. Methods and Findings: In this clinico-pathological case, we report a 90-year-old female who presented, at age 81, with a transient episode of generalized chorea. Over the years, the patient continued to have intermittent episodes of generalized chorea or hemichorea, followed by a progressive dementia syndrome with gait and sphincter disturbance. There was no family history of chorea or dementia. Laboratory tests for paraneoplastic or autoimmune disorders and genetic testing for Huntington's disease were normal or negative. Magnetic resonance imaging showed subcortical and basal ganglia atrophy associated with ischemic leukoencephalopathy and lacunar infarcts. The post-mortem examination identified multiple lacunar infarcts (cortex, white matter, thalamus, basal ganglia) and minor Alzheimer′s disease neuropathological changes. Conclusions: Vascular disease, affecting the basal ganglia, is included in most lists of causes of generalized chorea. Proven cases are difficult to find. We present a rare case of vascular pathology causing late onset generalized and intermittent chorea. We highlight the intermittent nature of the chorea that could be explained by cumulative vascular lesions or functional disconnection in a previous deficient circuit.",cyanocobalamin;donepezil;folic acid;haloperidol;iron;olanzapine;quetiapine;risperidone;aged;aggressiveness;article;atherosclerosis;brain atrophy;brain infarction;case report;caudate nucleus;cerebrovascular disease;chorea;clinical article;cognitive defect;dementia;dyskinesia;female;heart left ventricle hypertrophy;human;incontinence;iron deficiency;Mini Mental State Examination;nuclear magnetic resonance imaging;priority journal;very elderly;vitamin deficiency;white matter injury,"Salgado, P.;Taipa, R.;Domingos, J.;Dias, D.;Pires, M. M.;Magalhães, M.",2017,,10.1002/mdc3.12528,0,
1497,"Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: A double-blind, placebo-controlled, clinical and EEG/ERP mapping study","In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multi-infarct dementia (MID), based on computed tomography and Hachinski scores (≤49 SDAT, ≤7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC, SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable - the Clinical Global Impression (CGI) - a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (χ2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (χ2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.",ergot alkaloid;nicergoline;placebo;aged;alertness;Alzheimer disease;article;clinical trial;controlled study;double blind procedure;drug efficacy;electroencephalogram;evoked response;female;human;major clinical study;male;multiinfarct dementia;oral drug administration;randomized controlled trial;senile dementia;sermion,"Saletu, B.;Paulus, E.;Linzmayer, L.;Anderer, P.;Semlitsch, H. V.;Grunberger, J.;Wicke, L.;Neuhold, A.;Podreka, I.",1996,,,0,1498
1498,"Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: a double-blind, placebo-controlled, clinical and EEG/ERP mapping study","In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multiinfarct dementia (MID), based on computed tomography and Hachinski scores (< or = 49 SDAT, > or = 7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC. SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable-the Clinical Global Impression (CGI)-a significant superiority of Global Impression (CGI)-a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (chi 2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (chi 2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.","Alzheimer Disease/*drug therapy;Brain/*physiopathology;Brain Mapping;Dementia, Multi-Infarct/*drug therapy;Double-Blind Method;Electroencephalography;Evoked Potentials/physiology;Female;Humans;Male;Nicergoline/*therapeutic use;Psychiatric Status Rating Scales","Saletu, B.;Paulus, E.;Linzmayer, L.;Anderer, P.;Semlitsch, H. V.;Grunberger, J.;Wicke, L.;Neuhold, A.;Podreka, I.",1995,Feb,,0,
1499,"Nicergoline in senile dementia of Alzheimer type and multi-infarct dementia: A double blind, placebo controlled, clinical and EEG/ERP mapping study","Abstract In a double-blind, placebo-controlled study on the therapeutic efficacy and central effects of nicergoline, an ergot alkaloid with metabolic, antithrombotic and vasoactive action, 112 patients with mild to moderate dementia, diagnosed according to DSM III-R criteria (MMS 13-25), living in pensioners' homes, were included. Fifty-six were subdiagnosed as senile dementia of the Alzheimer type (SDAT), 56 as multi-infarct dementia (MID), based on computed tomography and Hachinski scores (≤ 49 SDAT, ≤ 7 MID). They received, after 2 weeks' run-in period (placebo), randomized for 8 weeks either 2 x 30 mg nicergoline (NIC) or 2 x 1 placebo (PLAC) orally. The four subgroups (SDAT/NIC, SDAT/PLAC, MID/NIC, MID/PLAC; 4 x 28 patients) were comparable in regard to age and sex. Only four, four, four and two patients of the respective groups did not finish the study for minor reasons. Confirmatory statistical analysis demonstrated in the target variable - the Clinical Global Impression (CGI)- a significant superiority of NIC over PLAC in both the SDAT and MID groups. Global improvement (CGI item 2) was seen in both nicergoline subgroups (3 and 3), while no changes occurred under placebo (4 and 4, respectively). The responder versus non-responder ratio was in the SDAT/NIC group 16/8, versus 8/16 in the SDAT/PLAC group (χ2 = 4.1, P = 0.04); in the MID/NIC group 17/7, versus 7/19 in the MID/PLAC group (χ2 = 7.96, P < 0.005). Furthermore, there was a significant improvement of the Mini-Mental State and the SCAG score in both the MID and SDAT group after 8 weeks of nicergoline, which was significantly superior to the minimal improvement or no change in placebo-treated SDAT and MID patients. EEG mapping demonstrated in NIC-treated SDAT and MID patients a significant decrease in delta and theta, increase in alpha 2 and beta activity and an acceleration of the centroid of the total power spectrum as compared with pretreatment, while opposite changes occurred in PLAC-treated SDAT and MID patients. The differences between PLAC and NIC reached the level of statistical significance. Event-related potential (ERP) recordings demonstrated a significantly shortened P300 latency under NIC treatment in both SDAT and MID patients, while there was a trend towards lengthening under PLAC. Thus, nicergoline improved vigilance and information processing at the neurophysiological level, which leads at the behavioural level to clinical improvement both in degenerative and vascular dementia.",ergot alkaloid;nicergoline;placebo;adult;aged;alertness;alpha rhythm;Alzheimer disease;article;beta rhythm;clinical trial;computer assisted tomography;controlled clinical trial;controlled study;delta rhythm;double blind procedure;drug response;electroencephalogram;evoked response;female;human;information processing;major clinical study;male;multiinfarct dementia;oral drug administration;power spectrum;priority journal;randomized controlled trial;senile dementia;theta rhythm;sermion,"Saletu, B.;Paulus, E.;Linzmayer, L.;Anderer, P.;Semlitsch, H. V.;Grunberger, J.;Wicke, L.;Neuhold, A.",1995,,,0,
1500,"[Therapy of multi-infarct dementia with nicergoline: double-blind, clinical, psychometric and EEG imaging studies with 2 dosage schedules] Zur Therapie der Multiinfarktdemenz mit Nicergolin1): doppelblinde, klinische, psychometrische und EEG-Imaginguntersuchungen mit 2 Dosierungsschemata","In a double-blind study, clinical, psychometric and neurophysiological changes were investigated in patients with MID treated by two different drug administration schedules of nicergoline (20 mg evenings versus 10 mg b.i.d.). 24 hospitalized patients (4 males, 20 females) with a mean age of 78 years were included according to the criteria of DSM-III, an Ischemic-Score of at least 7 points and a specific computed tomogram (CT). After a placebo-period of 2 weeks all patients were randomly assigned to an 8-weeks-treatment with either 20 mg nicergoline h.s. or 2 x 10 mg b.i.d. The evaluation of the detailed psychopathology by means of SCAG, CGI, NOSIE, Hamilton-Depressions-Scale and Mini-Mental-Status, as well as psychometric investigations by means of the Nuremberg-Aging-Inventory (NAI), thymophysic and psychophysiological measurements showed a significant improvement in both groups as compared with pre-treatment. This improvement was observed slightly earlier in patients with 20 mg h.s. than in those on the b.i.d. schedule. However inter-group-differences reached the level of statistical significance in only 2 variables. Neurophysiological investigations by means of topographic brain-mapping showed interesting relations between functional EEG-images and morphological CT-images. Vigilance-improving patients showed a better therapeutic response than those who did not show neurophysiological changes indicative of improvement in vigilance. Our findings suggest, that a single dose once daily was at least equal to the b.i.d. administration as far as therapeutic efficacy was concerned, even more so in the light of an expected improvement of compliance.","0 (Ergolines);JCV8365FWN (Nicergoline);Aged;Aged, 80 and over;Clinical Trials as Topic;Dementia/ drug therapy/psychology;Dose-Response Relationship, Drug;Double-Blind Method;Drug Administration Schedule;Electroencephalography;Ergolines/ therapeutic use;Evoked Potentials/drug effects;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Nicergoline/ therapeutic use;Psychometrics","Saletu, B.;Hochmayer, I.;Grunberger, J.;Bohmer, F.;Paroubek, J.;Wicke, L.;Neuhold, A.",1987,Nov 30,,0,
1501,"Therapy of multi-infarct-dementia with nicergoline: Double-blind, clinical, psychometric and EEG-imaging-investigation with two different drug administration schedules. <ORIGINAL> ZUR THERAPIE DER MULTIINFARKTDEMENZ MIT NICERGOLIN: DOPPELBLINDE, KLINISCHE, PSYCHOMETRISCHE UND EEG-IMAGINGUNTERSUCHUNGEN MIT 2 DOSIERUNGSSCHEMATA","In a double-blind study, clinical, psychometric and neurophysiological changes were investigated in patients with MID treated by two different drug administration schedules of nicergoline (20 mg evenings versus 10 mg b.i.d.). 24 hospitalized patients (4 males, 20 females) with a mean age of 78 years were included according to the criteria of DSM-III, an Ischemic-Score of at least 7 points and a specific computed tomogram (CT). After a placebo-period of 2 weeks all patients were randomly assigned to an 8-weeks-treatment with either 20 mg nicergoline h.s. or 2 x 10 mg b.i.d. The evaluation of the detailed psychopathology by means of SCAG, CGI, NOSIE, Hamilton-Depressions-Scale and Mini-Mental-Status, as well as psychometric investigations by means of the Nuremberg-Aging-Inventory (NAI), thymopsychic and psychophysiological measurements showed a significant improvement in both groups as compared with pre-treatment. This improvement was observed slightly earlier in patients with 20 mg h.s than in those on the b.i.d. schedule. However, inter-group-differences reached the level of statistical significance in only 2 variables. Neurophysiological investigations by means of topographic brain-mapping showed interesting relations between functional EEG-images and morphological CT-images. Vigilance-improving patients showed a better therapeutic response than those who did not show neurophysiological changes indicative of improvement in vigilance. Our findings suggest, that a single dose once daily was at least equal to the b.i.d. administration as far as therapeutic efficacy was concerned, even more so in the light of an expected improvement of compliance. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.",Nicergoline --Drug Therapy --Dt/ Nicergoline --Clinical Trial --Ct/ Nicergoline --Drug Dose --Do/ Dementia/ Electroencephalography/ Brain Ischemia/ Brain Infarction/ Brain Tomography,"Saletu, B.;Hochmayer, I.;Grunberger, J.;Bohmer, F.;Paroubek, J.;Wicke, L.;Neuhold, A.",1987,,,0,
1502,"Therapy of multi-infarct dementia with nicergoline: double-blind, clinical, psychometric and EEG imaging studies with 2 dosage schedules","In a double-blind study, clinical, psychometric and neurophysiological changes were investigated in patients with MID treated by two different drug administration schedules of nicergoline (20 mg evenings versus 10 mg b.i.d.). 24 hospitalized patients (4 males, 20 females) with a mean age of 78 years were included according to the criteria of DSM-III, an Ischemic-Score of at least 7 points and a specific computed tomogram (CT). After a placebo-period of 2 weeks all patients were randomly assigned to an 8-weeks-treatment with either 20 mg nicergoline h.s. or 2 x 10 mg b.i.d. The evaluation of the detailed psychopathology by means of SCAG, CGI, NOSIE, Hamilton-Depressions-Scale and Mini-Mental-Status, as well as psychometric investigations by means of the Nuremberg-Aging-Inventory (NAI), thymophysic and psychophysiological measurements showed a significant improvement in both groups as compared with pre-treatment. This improvement was observed slightly earlier in patients with 20 mg h.s. than in those on the b.i.d. schedule. However inter-group-differences reached the level of statistical significance in only 2 variables. Neurophysiological investigations by means of topographic brain-mapping showed interesting relations between functional EEG-images and morphological CT-images. Vigilance-improving patients showed a better therapeutic response than those who did not show neurophysiological changes indicative of improvement in vigilance. Our findings suggest, that a single dose once daily was at least equal to the b.i.d. administration as far as therapeutic efficacy was concerned, even more so in the light of an expected improvement of compliance.","Aged;Aged, 80 and over;Clinical Trials as Topic;Dementia/ drug therapy/psychology;Dose-Response Relationship, Drug;Double-Blind Method;Drug Administration Schedule;Electroencephalography;Ergolines/ therapeutic use;Evoked Potentials/drug effects;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Nicergoline/ therapeutic use;Psychometrics","Saletu, B.;Hochmayer, I.;Grunberger, J.;Bohmer, F.;Paroubek, J.;Wicke, L.;Neuhold, A.",1987,Nov 30,,0,
1503,EEG brain mapping in diagnostic and therapeutic assessment of dementia,"EEG brain mapping has been proven to be a valuable method in diagnostic and therapeutic assessment in dementia trials, because it is a readily available, inexpensive, high time-resolution method for objective and quantitative evaluation of the neurophysiological aspects of dementias. In 111 mildly to moderately demented patients diagnosed according to DSM-III as both degenerative [senile dementia of the Alzheimer type (SDAT)] and vascular [multi-infarct dementia (MID) type], we were interested in showing not only differences between SDAT and MID patients and normal controls but also the relationship between CT scans, EEG maps, clinical ratings and psychometric tests. CT measures included 10 cerebrospinal fluid (CSF) space variables as well as 17 cortical density measures (1.7 mm3 cubes, Hounsfield units). Clinical investigations consisted of the SCAG score/factors, the digit symbol substitution test, the trailmaking test and the digit span forward test. In brain maps, SDAT patients showed slightly to moderately more slow and less alpha and beta activity as well as a slowing of the dominant frequency (DF) and the centroid (C) than did normal controls. These findings were most prominent in parietal and temporal regions. MID patients exhibited markedly augmented delta/theta and attenuated alpha and beta activity and a slowing of the DF and C. These neurophysiological findings suggest a deterioration of vigilance. Differences between SDAT and MID patients were found mostly in measures concerning differences in the maps. Brain maps of correlation coefficients between CT and EEG variables demonstrated: the greater the anterior horn distance, lateral ventricle distance, and Evan's index, as well as the less cortical density, the more delta/theta and the less alpha and beta activity in the EEG. Moreover, the higher the delta/theta, the less alpha and beta activity, the higher the SCAG scores, and the worse the psychometric performance. From the pharmacological point of view, we observed a significant improvement in vigilance after administration of several nootropic drugs both in normal and pathologically aging subjects, which was associated also with improvement of psychopathometric scores. Based on multi-variante analysis of variance (MANOVA)/Hotlelling T2 we observed a drug's effect in different brain regions of MID and SDAT patients. Thus, pharmaco-EEG mapping mediates valuable information regarding if, how, when, in which dosage, and where a nootropic drug acts on its target organ--the aging human brain.","Aged;Alpha Rhythm/drug effects;Beta Rhythm/drug effects;*Brain Mapping;Clinical Trials as Topic;Dementia/*diagnosis/drug therapy;Dementia, Multi-Infarct/*diagnosis/drug therapy;Diagnostic Imaging;*Electroencephalography;Female;Humans;Male;Middle Aged;Psychological Tests;Psychotropic Drugs/therapeutic use;Tomography, X-Ray Computed","Saletu, B.;Anderer, P.;Paulus, E.;Grunberger, J.;Wicke, L.;Neuhold, A.;Fischhof, P. K.;Litschauer, G.",1991,,,0,
1504,EEG mapping and psychopharmacological studies with denbufylline in SDAT and MID,"Computed tomography (CT), electroencephalograms (EEG), clinical and psychometric data were obtained in 96 mildly to moderately demented patients (72 women, 24 men), aged 61-96 years (mean 82), diagnosed according to DSM-III criteria. Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type (SDAT) and 51 multiinfarct dementia (MID) patients. Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping, the Sandoz Clinical Assessment Geriatric (SCAG) score/factors, the Clinical Global Impression (CGI), the Digit Symbol Substitution Test (DSST), the Trail-Making Test (TMT) and the Digit Span Test (DS). Descriptive data analysis including confirmatory statements found delta/theta activity enhanced, alpha and beta activity reduced, total power augmented, and the centroid slowed down over various brain regions in patients as compared with controls. The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices. Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients, whereas after placebo this was not the case in CGI, the TMT, and the DS, with interdrug differences being significant in all primary target variables such as the CGI, MMS, SCAG, and DSST. Thus, both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance.","Alzheimer Disease [drug therapy] [physiopathology] [psychology];Attention [drug effects] [physiology];Brain Mapping [instrumentation];Cerebral Cortex [drug effects] [physiopathology];Dementia, Multi-Infarct [drug therapy] [physiopathology] [psychology];Double-Blind Method;Electroencephalography [drug effects] [instrumentation];Evoked Potentials [drug effects] [physiology];Neuropsychological Tests;Retention (Psychology) [drug effects] [physiology];Signal Processing, Computer-Assisted [instrumentation];Xanthines [therapeutic use];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia","Saletu, B.;Anderer, P.;Fischhof, P. K.;Lorenz, H.;Barousch, R.;Böhmer, F.",1992,,,0,
1505,White matter hyperintensities and prepulse inhibition in a mixed elderly population,"Prepulse inhibition (PPI) of the startle response, a measure for sensorimotor gating, exhibits a relatively high inter-individual variability in elderly subjects. The aim of this study was to investigate whether white matter hyperintensities (WMH), frequently identified on cranial magnetic resonance imaging (MRI) in elderly subjects with and without cognitive impairment, may contribute to variations in PPI. A passive acoustic PPI paradigm was applied in 92 human subjects (53 healthy and 39 patients with Alzheimer's disease or mild cognitive impairment) between 60 and 85years of age. WMH were rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related to the degree of WMH nor to cognitive performance. We conclude that the presence of WMH in the fronto-striatal brain circuit may affect the latency of the startle response, but not information processing in elderly subjects.","Acoustic Stimulation/adverse effects;Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Brain Mapping;Cognition Disorders/ pathology;Female;Humans;Inhibition (Psychology);Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reaction Time;Reflex, Startle/ physiology","Salem, L. C.;Hejl, A. M.;Garde, E.;Leffers, A. M.;Paulson, O. B.;Waldemar, G.",2011,Dec 30,10.1016/j.pscychresns.2011.07.007,0,
1506,Subcortical gray matter N-acetylaspartate reduction in two cases of vascular dementia,"Many of the previous studies of vascular dementia using proton magnetic resonance (MR) spectroscopy had been carried out on white matter. However, no proton spectroscopic data of the subcortical gray matter are available in such disease. We report two cases suffering from vascular dementia, with an unilateral N-acetylaspartate (NAA) decrease on subcortical gray matter. This significant reduction in NAA ratios was associated with an increase of choline on the ipsilateral centrum semiovale. We discuss the pathophysiology of these cases. © 2002 Elsevier Science Inc. All rights reserved.",captopril;choline;clopidogrel;glibenclamide;glyceryl trinitrate;n acetylaspartic acid;adult;aged;aphasia;arteriosclerosis;article;aspiration pneumonia;Binswanger encephalopathy;cardiovascular risk;carotid artery obstruction;case report;clinical feature;computer assisted tomography;diagnostic imaging;dysgraphia;dyslexia;female;gray matter;hemiparesis;human;hyperlipidemia;hypertension;ischemic heart disease;lifestyle;male;memory disorder;multiinfarct dementia;neurologic examination;non insulin dependent diabetes mellitus;pons;priority journal;proton nuclear magnetic resonance;pseudobulbar palsy,"Salem, D. B.;Walker, P. M.;Osseby, G. V.;Krausé, D.;Giroud, M.;Brunotte, F.",2003,,,0,
1507,"An epidemiological study of dementia under the aegis of mental health program, Maharashtra, Pune chapter","BACKGROUND: There has been an exponential growth in the number of elderly population in India. This study aims to determine the prevalence of dementia in an urban center of Pune and to evaluate the corresponding socio-demographic correlates along with psychiatric morbidity in the study sample. MATERIALS AND METHODS: The study population in Pune and Kirkee cantonments was selected based on 2001 census data. The number of people over 65 years numbered 6721 and 2145 of them were randomly selected for a door-to-door survey. They were initially administered household questionnaire and then subjected to a screening tool. Each participant underwent a brief mental state examination and data was collected on the basis of a structured proforma. Patients underwent a detailed cognitive profile using subtests from CSI-D (community screening instrument - dementia), which included a Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list, word fluency and delayed recall. Information pertaining to socio-demographic factors in participants and caregivers, caregiver-burden and behavioral and psychological symptoms in participants too were collected from the questionnaire. Radio imaging investigation was also carried out to quantify the deficit. Statistical Package for the Social Sciences (SPSS) software was used to compute the results. RESULTS: Findings revealed that prevalence of dementia in the sample population of elderly aged above 65 years was 4.1%. Socio-demographic factors which conferred a statistically higher risk for dementia were identified to be older age, low socio-economic status, low level of education, presence of family history, whereas, marriage was found to be protective. Burden of care was associated with caring for elderly with dementia with increasing severity of dementia. Patients with dementia performed poorly on cognitive test battery. Social network had a protective effect in respect with severity of dementia. On magnetic resonance imaging (MRI) majority of cases of Alzheimer's Dementia (AD) and Vascular Dementia (VaD) were noted to have both gray and white matter involvement. CONCLUSION: Poor awareness is a key public-health problem. Society plays an important role in the ageing process. The withdrawal of the elderly from the previous societal roles,reduction in all types of interactions i.e. shift of attention from outer world to the inner world, reduction in the power and prestige of the elderly enhance aging process. Aging in Indian culture though a disability is much stressful today in Indian culture as in others.",,"Saldanha, D.;Mani, M. R.;Srivastava, K.;Goyal, S.;Bhattacharya, D.",2010,Apr,10.4103/0019-5545.64588,0,
1508,White matter pathology isolates the hippocampal formation in Alzheimer's disease,"Prior work has demonstrated that the memory dysfunction of Alzheimer's disease (AD) is accompanied by marked cortical pathology in medial temporal lobe (MTL) gray matter. In contrast, changes in white matter (WM) of pathways associated with the MTL have rarely been studied. We used diffusion tensor imaging (DTI) to examine regional patterns of WM tissue changes in individuals with AD. Alterations of diffusion properties with AD were found in several regions including parahippocampal WM, and in regions with direct and secondary connections to the MTL. A portion of the changes measured, including effects in the parahippocampal WM, were independent of gray matter degeneration as measured by hippocampal volume. Examination of regional changes in unique diffusion parameters including anisotropy and axial and radial diffusivity demonstrated distinct zones of alterations, potentially stemming from differences in underlying pathology, with a potential myelin specific pathology in the parahippocampal WM. These results demonstrate that deterioration of neocortical connections to the hippocampal formation results in part from the degeneration of critical MTL and associated fiber pathways.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/pathology;Diffusion Tensor Imaging;Female;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted;Male;Nerve Fibers, Myelinated/ pathology;Nerve Fibers, Unmyelinated/pathology;Neural Pathways/pathology;Organ Size;Parahippocampal Gyrus/pathology","Salat, D. H.;Tuch, D. S.;van der Kouwe, A. J.;Greve, D. N.;Pappu, V.;Lee, S. Y.;Hevelone, N. D.;Zaleta, A. K.;Growdon, J. H.;Corkin, S.;Fischl, B.;Rosas, H. D.",2010,Feb,10.1016/j.neurobiolaging.2008.03.013,0,
1509,Sex differences in prefrontal volume with aging and Alzheimer's disease,"We used volumetric magnetic resonance imaging to examine sex differences in prefrontal tissue volumes of healthy aged and patients with Alzheimer's disease (AD). Healthy subjects had greater total prefrontal volume than AD, and men had greater total prefrontal volume than women (ps < or = 0.02). This was true for both gray and white matter volumes. There were no interactions between group and sex for total prefrontal volume. An exploratory analysis of each group suggested that sex differences in both gray and white matter in healthy aging are not sustained in AD.",Aged;Alzheimer Disease/ pathology;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Sex Characteristics,"Salat, D. H.;Stangl, P. A.;Kaye, J. A.;Janowsky, J. S.",1999,Nov-Dec,,0,
1510,White matter alterations in cerebral amyloid angiopathy measured by diffusion tensor imaging,"BACKGROUND AND PURPOSE - Cerebral amyloid angiopathy (CAA) represents β-amyloid deposition in the small- and medium-sized vessels of the brain and meninges. CAA contributes to altered vessel function and is associated with white matter damage, cognitive impairment, and most salient, hemorrhagic stroke. We used diffusion tensor imaging to evaluate the anatomic distribution of white matter degeneration in participants diagnosed with advanced CAA. METHODS - Diffusion tensor imaging was obtained from 11 participants diagnosed with CAA-related intracerebral hemorrhage and 13 matched healthy control participants. Fractional anisotropy (FA) and diffusivity maps were compared using voxel based t test and region-of-interest analyses. RESULTS - FA was reduced in CAA in temporal white matter and in the splenium of the corpus callosum (P<0.001 with ≈17% reduction in temporal white matter and 15% reduction in the splenium). FA was marginally increased in CAA in the posterior limb of the internal capsule and subthalamic gray matter regions (≈7% increase in subthalamic gray). FA changes were bilateral, remained significant in cluster analysis controlling for multiple comparisons, and did not depend on the hemisphere of the cerebral hemorrhage. Diffusivity was not substantially altered. CONCLUSIONS - These findings suggest that a pattern of regional brain tissue degeneration is a characteristic feature of advanced CAA. © 2006 American Heart Association, Inc.",,"Salat, D. H.;Smith, E. E.;Tuch, D. S.;Benner, T.;Pappu, V.;Schwab, K. M.;Gurol, M. E.;Rosas, H. D.;Rosand, J.;Greenberg, S. M.",2006,July,,0,
1511,Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast,"Prior studies have focused on patterns of brain atrophy with aging and age-associated cognitive decline. It is possible that changes in neural tissue properties could provide an important marker of more subtle changes compared to gross morphometry. However, little is known about how MRI tissue parameters are altered in aging. We created cortical surface models of 148 individuals and mapped regional gray and white matter T1-weighted signal intensities from 3D MPRAGE images to examine patterns of age-associated signal alterations. Gray matter intensity was decreased with aging with strongest effects in medial frontal, anterior cingulate, and inferior temporal regions. White matter signal intensity decreased with aging in superior and medial frontal, cingulum, and medial and lateral temporal regions. The gray/white ratio (GWR) was altered throughout a large portion of the cortical mantle, with strong changes in superior and inferior frontal, lateral parietal, and superior temporal and precuneus regions demonstrating decreased overall contrast. Statistical effects of contrast changes were stronger than those of cortical thinning. These results demonstrate that there are strong regional changes in neural tissue properties with aging and tissue intensity measures may serve as an important biomarker of degeneration.",,"Salat, D. H.;Lee, S. Y.;van der Kouwe, A. J.;Greve, D. N.;Fischl, B.;Rosas, H. D.",2009,15,,0,
1512,Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease,"Background: The prefrontal cortex (PFC) is a heterogeneous cortical structure that supports higher cognitive functions, including working memory and verbal abilities. The PFC is vulnerable to neurodegeneration with healthy aging and Alzheimer disease (AD). Objective: We used volumetric magnetic resonance imaging to determine whether any region within the PFC is more vulnerable to deterioration with late aging or AD. Methods: Volumetric analysis of PFC regions was performed on younger healthy elderly subjects (n = 26; 14 men and 12 women [mean age, 71.7 years] for aging analysis; 12 men and 14 women [mean age, 71.4 years] for AD analysis), oldest healthy elderly (OHE) subjects (n = 22 [11 men and 11 women]; mean age, 88.9 years), and patients with AD (n = 22 [12 men and 10 women]; mean age, 69.8 years). Results: The OHE subjects had less PFC white matter than did young healthy elderly subjects. The orbital region was selectively preserved relative to other PFC regions in the OHE subjects. Subjects with AD had less total PFC gray matter than did age-matched healthy subjects and significantly less volume in the inferior PFC region only. Conclusions: Orbital PFC is selectively preserved in OHE subjects. In contrast, degeneration within the PFC with AD is most prominent in the inferior PFC region. Thus, degeneration within the PFC has a regionally distinct pattern in healthy aging and AD.",,"Salat, D. H.;Kaye, J. A.;Janowsky, J. S.",2001,2001,,0,
1513,Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease,"Objectives: To quantify the contribution of gray and white matter volumes to total prefrontal volume in healthy aging. To determine if prefrontal tissue volumes distinguish healthy aging from Alzheimer disease (AD). Design: Volumes of total prefrontal cortex, prefrontal gray matter, and prefrontal white matter were compared among young healthy elderly (YHE) (n = 14; mean age, 70 years), old healthy elderly (OHE) (n = 14; mean age, 90 years), and subjects with AD (n = 14; mean age, 70 years) by analysis of variance. Additionally, Pearson correlations were performed between volumes and age. Results: Old healthy elderly and subjects with AD had significantly less total prefrontal volume (approximately 15% less in both groups) and prefrontal white matter volume (approximately 30% less and 20% less in the OHE and AD groups, respectively) than YHE, but there were no differences between the OHE and AD groups. There was a significant difference in gray- white matter volume ratio with OHE having a higher ratio than YHE. Subjects with AD did not differ from YHE or OHE in this ratio. There were significant negative correlations between age and total prefrontal volume and age and prefrontal white matter volume in the healthy subjects. Conclusions: In the very old, the decline of white matter volume is disproportionately greater than the decline of gray matter volume. In subjects with AD both gray and white matter loss contribute to the decline of prefrontal volume. This is demonstrated by the gray-white matter ratio that does not differ between YHE and subjects with AD. Thus, it is likely that AD is different from accelerated aging.",adult;aged;aging;Alzheimer disease;article;brain size;clinical article;controlled study;female;gray matter;human;male;nuclear magnetic resonance imaging;prefrontal cortex;priority journal;white matter,"Salat, D. H.;Kaye, J. A.;Janowsky, J. S.",1999,,,0,
1514,Regional white matter volume differences in nondemented aging and Alzheimer's disease,"Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.","Aged;Aging/*pathology;Alzheimer Disease/*pathology;Brain/*pathology;Dementia/*pathology;Female;Humans;Imaging, Three-Dimensional/*methods;Magnetic Resonance Imaging/*methods;Male;Nerve Fibers, Myelinated/*pathology;Young Adult","Salat, D. H.;Greve, D. N.;Pacheco, J. L.;Quinn, B. T.;Helmer, K. G.;Buckner, R. L.;Fischl, B.",2009,Feb 15,10.1016/j.neuroimage.2008.10.030,0,
1515,Hippocampal degeneration is associated with temporal and limbic gray matter/white matter tissue contrast in Alzheimer's disease,"Recent studies have demonstrated alterations in cortical gray to white matter tissue contrast with nondemented aging and in individuals with Alzheimer's disease (AD). However, little information exists about the clinical relevance of such changes. It is possible that changes in MRI tissue contrast occur via independent mechanisms from those traditionally used in the assessment of AD associated degeneration such as hippocampal degeneration measured by more traditional volumetric magnetic resonance imaging (MRI). We created cortical surface models of 95 cognitively healthy individuals and 98 individuals with AD to characterize changes in regional gray and white matter T1-weighted signal intensities in dementia and to evaluate how such measures related to classically described hippocampal and cortical atrophy. We found a reduction in gray matter to white matter tissue contrast throughout portions of medial and lateral temporal cortical regions as well as in anatomically associated regions including the posterior cingulate, precuneus, and medial frontal cortex. Decreases in tissue contrast were associated with hippocampal volume, however, the regional patterns of these associations differed for demented and nondemented individuals. In nondemented controls, lower hippocampal volume was associated with decreased gray/white matter tissue contrast globally across the cortical mantle. In contrast, in individuals with AD, selective associations were found between hippocampal volume and tissue contrast in temporal and limbic tissue. These results demonstrate that there are strong regional changes in neural tissue properties in AD which follow a spatial pattern including regions known to be affected from pathology studies. Such changes are associated with traditional imaging metrics of degeneration and may provide a unique biomarker of the tissue loss that occurs as a result of AD.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/ pathology/psychology;Entorhinal Cortex/pathology;Female;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted;Limbic System/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/ pathology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Parahippocampal Gyrus/pathology;Reproducibility of Results;Temporal Lobe/ pathology","Salat, D. H.;Chen, J. J.;van der Kouwe, A. J.;Greve, D. N.;Fischl, B.;Rosas, H. D.",2011,Feb 1,10.1016/j.neuroimage.2010.10.034,0,
1516,Post-anoxic delayed encephalopathy with leukoencephalopathy and non-hemorrhagic cerebral amyloid angiopathy,"A 74 year-old woman with an early-stage senile dementia developed severe hypertonia and akinetic mutism two weeks after exposure to methane. A CT scan showed a diffuse area of decreased density extending symmetrically into the white matter of both cerebral hemispheres. Neuropathology revealed a senile dementia, Alzheimer's type, with severe non-hemorrhagic cerebral amyloid angiopathy and a diffuse spotty demyelination of the cerebral hemispheres sparing the U fibers, corpus callosum and internal capsules. The close resemblance between Grinker's myelinopathy, secondary to CO exposure or to other non-CO anoxic causes, and the leukoencephalopathy associated with cerebral amyloid angiopathy is emphasized.",methane;amyloidosis;autopsy;brain disease;brain hypoxia;case report;central nervous system;cerebrovascular disease;computer analysis;computer assisted tomography;dementia;diagnosis;histology;human;leukoencephalopathy;nervous system;neuropathology;peripheral vascular system,"Salama, J.;Gherardi, R.;Amiel, H.",1986,,,0,
1517,Combining MRI modalities to study visual and default-mode networks in a-MCI,"Patients with pure amnestic MCI (a-MCI) are reported to have cognitively preserved visual processing skills. However, functional and anatomical abnormalities and/or reorganizations might be already detectable in the brain networks that underlie these cognitive functions. To investigate this possibility, we conducted an integrated multi-modal MRI study using task-fMRI, high resolution structural MRI and Diffusion Tensor Imaging (DTI) in 15 a-MCI patients and 15 matched Healthy Elders (HE). Using fMRI data, we identified an Activation Task Related Pattern (ATRP), including areas related to complex visual processing, and a Deactivation Task Related Pattern (DTRP), or default-mode network (DMN). These two networks were further characterized regarding their structural properties (gray matter volumes and white matter pathways). Within the ATRP, we found increased fMRI responses for the a-MCI group in the frontal lobe, and greater involvement of ventral visual areas. However, there were no differences in ATRP-related white matter or gray matter measures. Regarding the DTRP, a-MCI showed spatial functional reorganizations in coincidence with those reported in DMN studies. Moreover, structural abnormalities in a-MCI patients were clearly found in the DTRP (reduced GM volumes and less fiber tract integrity). In summary, the work presented here highlights the importance of conducting integrated multi-modal MRI studies in early stages of dementia based on spared cognitive domains in order to identify incipient functional abnormalities in critical areas of the DMN and their precise anatomical substrates, possibly reflecting early neuroimaging biomarkers in dementia. © 2011 The authors and IOS Press. All rights reserved.",,"Sala-Llonch, R.;Bosch, B.;Arenaza-Urquijo, E. M.;Rami, L.;Bargalló, N.;Junqué, C.;Molinuevo, J. L.;Bartrés-Faz, D.",2011,2011,,0,
1518,Greater default-mode network abnormalities compared to high order visual processing systems in amnestic mild cognitive impairment: An integrated multi-modal MRI study,"We conducted an integrated multi-modal magnetic resonance imaging (MRI) study based on functional MRI (fMRI) data during a complex but cognitively preserved visual task in 15 amnestic mild cognitive impairment (a-MCI) patients and 15 Healthy Elders (HE). Independent Component Analysis of fMRI data identified a functional network containing an Activation Task Related Pattern (ATRP), including regions of the dorsal and ventral visual stream, and a Deactivation Task Related Pattern network (DTRP), with high spatial correspondence with the default-mode network (DMN). Gray matter (GM) volumes of the underlying ATRP and DTRP cortical areas were measured, and probabilistic tractography (based on diffusion MRI) identified fiber pathways within each functional network. For the ATRP network, a-MCI patients exhibited increased fMRI responses in inferior-ventral visual areas, possibly reflecting compensatory activations for more compromised dorsal regions. However, no significant GM or white matter group differences were observed within the ATRP network. For the DTRP/DMN, a-MCI showed deactivation deficits and reduced GM volumes in the posterior cingulate/precuneus, excessive deactivations in the inferior parietal lobe, and less fiber tract integrity in the cingulate bundles. Task performance correlated with DTRP-functionality in the HE group. Besides allowing the identification of functional reorganizations in the cortical network directly processing the task-stimuli, these findings highlight the importance of conducting integrated multi-modal MRI studies in MCI based on spared cognitive domains in order to identify functional abnormalities in critical areas of the DMN and their precise anatomical substrates. These latter findings may reflect early neuroimaging biomarkers in dementia. © 2010 - IOS Press and the authors. All rights reserved.",,"Sala-Llonch, R.;Bosch, B.;Arenaza-Urquijo, E. M.;Rami, L.;Bargalló, N.;Junqué, C.;Molinuevo, J. L.;Bartrés-Faz, D.",2010,2010,,0,
1519,Radiolabeling of 18F -fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors,"INTRODUCTION: The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state. METHODS: Radiosynthesis was carried out using the Raytest(R) SynChrom R&D fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS(R) software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining. RESULTS: Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145 MBq and a specific activity above 355 GBq/mumol. Affinity assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN concentration gradually increased in the brain, stabilizing at 40 minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622, p<0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine. CONCLUSIONS: [(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders.","Animals;Autoradiography;Brain/ metabolism/ radionuclide imaging;Fluorine Radioisotopes/pharmacokinetics;Isotope Labeling;Kinetics;Male;Memantine/ analogs & derivatives/ pharmacokinetics;Metabolic Clearance Rate;Phencyclidine/ metabolism;Positron-Emission Tomography/ methods;Radiopharmaceuticals/ pharmacokinetics;Rats;Rats, Sprague-Dawley;Receptors, N-Methyl-D-Aspartate/ metabolism;Tissue Distribution","Salabert, A. S.;Fonta, C.;Fontan, C.;Adel, D.;Alonso, M.;Pestourie, C.;Belhadj-Tahar, H.;Tafani, M.;Payoux, P.",2015,Aug,10.1016/j.nucmedbio.2015.04.001,0,
1520,Lower vitamin D is associated with white matter hyperintensity in elderly women with Alzheimer's disease and amnestic mild cognitive impairment,,Aged;Alzheimer Disease/*pathology;Female;Humans;Hypertension/epidemiology;Magnetic Resonance Imaging;Mild Cognitive Impairment/*pathology;Neuropsychological Tests;Vitamin D/*analogs & derivatives/blood;White Matter/*pathology,"Sakurai, T.;Ogama, N.;Toba, K.",2014,Oct,10.1111/jgs.13048,0,
1521,The feasibility of white matter volume reduction analysis using SPM8 plus DARTEL for the diagnosis of patients with clinically diagnosed corticobasal syndrome and Richardson's syndrome,"PURPOSE: Diagnosing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is often difficult due to the wide variety of symptoms and overlaps in the similar clinical courses and neurological findings. The purpose of this study was to evaluate the utility of white matter (WM) atrophy for the diagnosis of patients with clinically diagnosed CBD (corticobasal syndrome, CBS) and PSP (Richardson's syndrome, RS). METHODS: We randomly divided the 3D T1-weighted MR images of 18 CBS patients, 33 RS patients, and 32 age-matched controls into two groups. We obtained segmented WM images in the first group using Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping (SPM) 8 plus diffeomorphic anatomical registration through exponentiated Lie algebra. A target volume of interest (VOI) for disease-specific atrophy was subsequently determined in this group using SPM8 group analyses of WM atrophy between patients groups and controls. We then evaluated the utility of these VOIs for diagnosing CBS and RS patients in the second group. Z score values in these VOIs were used as the determinant in receiver operating characteristic (ROC) analyses. RESULTS: Specific target VOIs were determined in the bilateral frontal subcortical WM for CBS and in the midbrain tegmentum for RS. In ROC analyses, the target VOIs of CBS and RS compared to those of controls exhibited an area under curve (AUC) of 0.99 and 0.84, respectively, which indicated an adequate diagnostic power. The VOI of CBS revealed a higher AUC than that of RS for differentiating between CBS and RS (AUC, 0.75 vs 0.53). CONCLUSIONS: Bilateral frontal WM volume reduction demonstrated a higher power for differentiating CBS from RS. This VOI analysis is useful for clinically diagnosing CBS and RS.","Aged;Aged, 80 and over;Area Under Curve;Atrophy;Basal Ganglia Diseases/ diagnosis/pathology;Brain Diseases/diagnosis/pathology;Case-Control Studies;Feasibility Studies;Female;Humans;Image Processing, Computer-Assisted/ methods;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Organ Size;ROC Curve;Sensitivity and Specificity;Supranuclear Palsy, Progressive/ diagnosis/pathology;Syndrome;White Matter/ pathology","Sakurai, K.;Imabayashi, E.;Tokumaru, A. M.;Hasebe, S.;Murayama, S.;Morimoto, S.;Kanemaru, K.;Takao, M.;Shibamoto, Y.;Matsukawa, N.",2015,,10.1016/j.nicl.2014.02.009,0,
1522,Abnormal copper metabolism in Niemann-Pick disease type C mimicking Wilson's disease,"Background: Niemann-Pick disease type C is a rare lysosomal storage disease in infants, adolescents and adults. Aim: We investigated a family with two siblings who have adult-onset Niemann-Pick disease type C presenting with abnormal copper metabolism mimicking Wilson's disease. Methods: Case 1 was a 26-years-old Japanese man without consanguinity, and was referred to the hospital outpatient clinic for recent gait disturbance and intellectual deterioration developing since the age of 20 years. He was tentatively diagnosed as a heterozygous carrier of Wilson's disease, because his brother (case 2) had been diagnosed with Wilson's disease. He presented with dementia, dysphagia, dystonia, ataxia and downward gaze palsy. Laboratory study showed mild liver dysfunction and moderate splenomegaly. Magnetic resonance images showed a thin corpus callosum and narrowed deep white matter. Case 2 35 years-of-age, and had developed psychiatric and motor symptoms since 20 years-of-age. He had been treated for Wilson's disease for 11 years due to a copper deposit in his liver and abnormal copper metabolism. Symptoms had exacerbated gradually despite chelation therapy and tube feeding with gastrostomy for a year. Molecular diagnostics for Niemann-Pick disease type C were carried out. Results: Filipin staining in cultured skin fibroblasts of case 1 was partially positive, and gene analysis showed that both siblings had compound heterozygosity for p.G992R in exon 20 and IVS6-3 C>G of NPC1. Administration of miglustat for 3 months partially ameliorated their intellectual and motor dysfunction. Conclusion: The differential diagnosis between Niemann-Pick disease type C and Wilson's disease is important for specific treatment.",,"Sakiyama, Y.;Narita, A.;Osawa, S.;Nanba, E.;Ohno, K.;Otsuka, M.",2014,1,,0,
1523,New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole treatment in Japan,"OBJECTIVE: To determine the causative pathogen and investigate the effective treatment of a new type of encephalomyelitis with an unknown pathogen in Japan and report the preliminary ultrastructural and genomic characterization of the causative agent. METHODS: From 2005 to 2012, we treated 4 Japanese patients with geographic clustering and comparable clinical features, serum/CSF cytology, and radiologic findings. Brain biopsy was conducted in all patients to analyze neuropathologic changes by histology, and electron microscopy was applied to reveal the features of the putative pathogen. Genomic DNA was obtained from the affected brain tissues and CSF, and an unbiased high-throughput sequencing approach was used to screen for specific genomic sequences indicative of the pathogen origin. RESULTS: All patients exhibited progressive dementia with involuntary tongue movements. Cytologic examination of CSF revealed elevated mononuclear cells. Abnormal MRI signals were observed in temporal lobes, subcortical white matter, and spinal cord. Biopsied brain tissue exhibited aggregated periodic acid-Schiff-positive macrophages and 2-7 mum diameter round/oval bodies without nuclei or cell walls scattered around the vessels. Unbiased high-throughput sequencing identified more than 100 archaea-specific DNA fragments. All patients were responsive to trimethoprim/sulfamethoxazole (TMP-SMX) plus corticosteroid therapy. CONCLUSIONS: We report 4 cases of encephalomyelitis due to an unknown pathogen. On the basis of ultrastructural and genomic studies, we propose a new disease entity resulting from a causative pathogen having archaeal features. TMP-SMX therapy was effective against this new type of encephalomyelitis.",,"Sakiyama, Y.;Kanda, N.;Higuchi, Y.;Yoshimura, M.;Wakaguri, H.;Takata, Y.;Watanabe, O.;Yuan, J.;Tashiro, Y.;Saigo, R.;Nozuma, S.;Yoshimura, A.;Arishima, S.;Ikeda, K.;Shinohara, K.;Arata, H.;Michizono, K.;Higashi, K.;Hashiguchi, A.;Okamoto, Y.;Hirano, R.;Shiraishi, T.;Matsuura, E.;Okubo, R.;Higuchi, I.;Goto, M.;Hirano, H.;Sano, A.;Iwasaki, T.;Matsuda, F.;Izumo, S.;Takashima, H.",2015,Oct,10.1212/nxi.0000000000000143,0,
1524,Studies of cerebral blood flow and metabolism in patients with senile dementia of the Alzheimer's type and diagnostic evaluation of the dementing illnesses by positron emission tomography,"This study was designed to estimate cerebral dysfunction in senile dementia of the Alzheimer's type (SDAT). Regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF) and cerebral oxygen consumption (rCMRO2) were studied in 16 patients with SDAT and 5 age-matched normal elderly people by positron emission tomography (PET), using the 15O labeled CO2 and O2 inhalation technique. This technique was also applied to the evaluation of PET in diagnosing the dementing illnesses. In this study, a total of 19 pairs of bilateral cerebral regions were analyzed and the reductions of rCBF and rCMRO2 in each region were compared with those of the primary sensorimotor cortex to demonstrate any significant localized difference between each clinical stage of the SDAT and normal controls. In the mild SDAT group, CMRO2 of the temporal cortex was significantly reduced, as compared with that of controls. In the moderate SDAT group, CBF of the temporal cortex and CMRO2 of the temporal and parietal cortices were significantly reduced. In the severe SDAT group, CBF and CMRO2 of the frontal cortex were also reduced and those of the occipital cortex were relatively unchanged. This suggested that mildly demented patients showed a metabolic reduction in the temporal cortex and as the dementia progressed, metabolic reductions were extended to the parietal and frontal cortices. Reductions in blood flow were followed by further metabolic reductions. More detailed investigation of the PET images of SDAT revealed that relative oxygen hypometabolism of the posterior temporal and posterior parietal association cortices occurred in the mildly demented patients earlier than that of the other association cortices. These findings are consistent with neuropathological studies of SDAT. The right/left ratio of rCMRO2 was also analyzed in each region. The right/left oxygen metabolic asymmetry in the temporal and parietal cortices was correlated with the difference between speech and visuospatial functions. Namely, the patients with a lower metabolism in the left hemisphere had more disturbances in speech than visuospatial functions. In addition, the PET images of SDAT were compared with those of multi-infarct dementia (MID) and Pick disease. In patients with MID, there were reductions of CBF and CMRO2 unhomogenously all over association cortices, but the reductions were most remarkable in the frontal cortex. Patients with Pick disease showed diffuse lobar reductions of CBF and CMRO2 in the frontal and temporal cortices.(ABSTRACT TRUNCATED AT 400 WORDS)",,"Sakamoto, S.",1990,Jun,,0,
1525,A case of intravascular large B-cell lymphoma with rapidly progressive cognitive impairment after cerebral infarction,"A 67-year-old man started to show symptoms of dementia and developed convulsions accompanied by presyncope. Since an old cerebral infarction was found, he was given a diagnosis of symptomatic epilepsy, treated with antiepileptics. Dementia progressed rapidly, resulting in admission to a dementia ward. There were no physical abnormalities, and only slight elevations of LDH and CRP were noted. He suddenly developed a fever between 38°C and 39°C. Only the serum concentration of soluble IL-2 receptor was elevated at 6,430 U/L. Although a malignant tumor of the lymphatic system was suspected, there was no swelling noted in the superficial lymph nodes. The patient suddenly developed hypoxemia, thrombocytopenia, and an increase in fibrin degradation products. Pulmonary thromboembolism was suspected, but contrast-enhanced chest CT did not reveal any abnormalities. Bone marrow aspiration did not detect any infiltrations of lymphoid cells but was suggestive of hemophagocytic syndrome. After that, a new cerebral infarction occurred. Based on the course, intravascular lymphoma, which causes microvascular occlusions in various organs, was considered probable. Prednisolone was administered at a dose of 60 mg daily and skin biopsy was scheduled. However, the patient experienced a sudden deterioration and died. In autopsy, immunostain with CD20 showed that the arteriolae, capillaries, and venulae of thoracic and abdominal organs were filled with cells of large B-cell lymphoma. The presence of similar cerebrovascular lesions was not confirmed, but can reasonably be speculated. Thus, the present case suggests that it is necessary to consider intravascular lymphoma when dementia rapidly progresses for unknown reasons.",aged;article;brain infarction;case report;cognitive defect;human;large cell lymphoma;male;pathology;vascular tumor,"Sakamoto, N.;Aiba, M.;Takahashi, M.;Sakurai, T.;Yang, K. S.;Tsuda, H.",2012,,,0,
1526,Micturitional disturbance in a patient with adrenomyeloneuropathy (AMN),"We report a case of adrenomyeloneuropathy (AMN) in which serial urodynamic studies showed neurogenic bladder dysfunction. The patient was in good health until the age of 12, when he began to lose his hair. At age 25 he started to have urinary urgency, difficulty in voiding, occasional fecal incontinence, erectile impotence, and progressive gait disturbance. In his first admission to our hospital age 31, he was intelligent but childish. He showed diffuse baldness, spastic paraparesis, and disturbed vibratory sensation. Serum cortisol response to corticotropin (ACTH) was low and serum levels of very long chain fatty acids were increased. Nerve conduction studies and sural nerve biopsy showed the presence of peripheral neuropathy. These findings confirmed the diagnosis of AMN. The first urodynamic study showed residual urine volume of 50 ml, impaired bladder sensation, and detrusor hyperreflexia. At age 38 he needed diapers because he became apathetic and demented, and could no longer stand by himself. MRI disclosed high signal intensities in the bilateral cerebral white matter. The second urodynamic study showed residual urine volume of 200 ml and decreased bladder capacity with marked detrusor hyperreflexia. Demyelinating lesions of the peripheral nerve and white matter of the spinal cord and the cerebrum may be mainly responsible for the micturitional disturbance in our patient with AMN.",adrenal insufficiency;adult;article;case report;human;hydrocortisone blood level;male;micturition disorder;nerve conduction;neurogenic bladder;nuclear magnetic resonance imaging;spastic paresis;spinal cord disease;urodynamics,"Sakakibara, R.;Hattori, T.;Fukutake, T.;Mori, M.;Yamanishi, T.;Yasuda, K.",1998,,,0,
1527,Cerebral amyloid angiopathy,"Cerebral amyloid angiopathy (CAA) is a disorder characterized by the accumulation of amyloid proteins in the small and medium-sized blood vessels of the leptomeninges and central nervous system. Amyloid beta protein (Abeta), immunoglobulin light chains, cystatin C, prion protein (PrP), ABri/ADan, transthyretin, and gelsoline, are all associated with CAA. While most CAA patients demonstrated sporadic Abeta-type amyloid deposition, a small number of patients present with familial forms, e.g. Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D), Icelandic-type HCHWA (HCHWA-I), familial British dementia (FBD), familial Danish dementia (FDD), and PrP-CAA. Deposited amyloid proteins damage smooth muscle cells in blood vessel walls leading to pathological appearances calling 'double-barreled' changes, fibrinoid necrosis, and microaneurysms. These structural abnormalities result in microinfarcts and hemorrhages in the central nervous system. Recurrent hemorrhage is a common clinical manifestation in patients with CAA; however, small multiple infarctions, progressive dementia, transient neurological symptoms, and CAA-related inflammation can also occur. The pathomechanisms of CAA remain unknown. Although improvements in imaging techniques have allowed us to identify patients with CAA more readily, pathological examination is still essential for a definite diagnosis. There have been no curative treatments for CAA so far.",Amyloid beta-Peptides/metabolism;Cerebral Amyloid Angiopathy/complications/metabolism/ pathology/therapy;Cystatin C/metabolism;Dementia/etiology;Humans;Mutation;Prealbumin/metabolism;Prognosis,"Sakai, K.;Yamada, M.",2014,Jul,,0,
1528,"Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes","We report two sporadic cases of tauopathy with unusual neuropathological features. The ages of the patients at death were 86 and 74 years, and the disease durations were 4 and 3 years, respectively. The former patient showed progressive dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was responsible for the amyotrophy), and the latter showed progressive parkinsonism and dementia. The essential brain pathologies were similar to each other; although ballooned neurons and astrocytic tau lesions (astrocytic plaques) were present in the affected cerebral cortex, the most striking finding was focal, much heavier accumulation of tau in the subcortical white matter. Moreover, double-labeling immunostaining, as well as Gallyas-Braak electron and AT8 immunoelectron microscopic studies strongly suggested that in the affected subcortical white matter, the accumulation of tau occurred mainly in the astrocytic processes. In the latter patient, for whom frozen brain tissue was available, immunoblotting of insoluble tau revealed a pattern compatible with that obtained from brain affected by typical corticobasal degeneration (CBD), and gene analysis of tau revealed no mutations, with a H1 haplotype. Finally, in both cases, the pathological diagnosis of CBD was considered to be appropriate. However, the tau pathology affecting the subcortical white matter astrocytes was very unusual for the disease. © Springer-Verlag 2006.",tau protein;aged;agraphia;amyotrophic lateral sclerosis;apraxia;article;astrocyte;autopsy;bradykinesia;brain cortex;brain tissue;case report;cell damage;cervical spondylosis;controlled study;corticobasal degeneration;dementia;diagnostic error;differential diagnosis;disease duration;electron microscopy;frozen section;gait disorder;gene mutation;genetic analysis;haplotype;hospital admission;human;human cell;human tissue;immunoblotting;immunoelectron microscopy;immunohistochemistry;intervertebral disk hernia;laminectomy;male;memory disorder;muscle atrophy;nerve cell;nuclear magnetic resonance imaging;parkinsonism;priority journal;protein localization;Shy Drager syndrome;tauopathy;urine incontinence;white matter,"Sakai, K.;Piao, Y. S.;Kikugawa, K.;Ohara, S.;Hasegawa, M.;Takano, H.;Fukase, M.;Nishizawa, M.;Kakita, A.;Takahashi, H.",2006,,,0,
1529,Transient elevation of the number of microembolic signal in a patient with primary antiphospholipid antibody syndrome,"We report a 55-year-old man complaining of monoparesis of the right arm and dementia. Brain magnetic resonance imaging (MRI) demonstrated multiple foci of fresh cerebral embolism. The serum lupus anticoagulant was positive, however, the serum anticardiolipin antibody and other autoantibodies indicating connective tissue diseases were negative. This patient received a diagnosis of primary antiphospholipid antibody syndrome. Transcranial Doppler (TCD) monitoring of the middle cerebral artery showed the presence of microembolic signal (MES). We initiated anticoagulant therapy with intravenous heparin administration, and three days later we added oral warfarin administration. We used both warfarin and heparin together for only three days. The number of MES increased transiently after initiating of warfarin administration, then decreased by warfarin therapy with production of an international normalized ratio (INR) of prothrombin time over 2. His neurological symptoms normalized except for monoparesis of the right arm. There were no foci of fresh cerebral infarct disclosed on brain MRI performed two months after admission. The treatment strategy for antiphospholipid antibody (APS) patients has not yet been established. Some reports and guideline recommended that the stroke patients with APS should be treated with long-term oral anticoagulant therapy, target INR 2.5 (optimal range 2.0 to 3.0). In this patient, we confirmed a decrease in the number of MES by warfarin therapy with production of INR over 2. In APS patients, detection of MES by TCD is a useful device for adjustment of the warfarin dose. Concerning the course of MES and warfarin therapy, transient elevation of the number of MES after initiation of warfarin therapy would suggest the hypercoagulability due to an acute decrease in serum protein C level. Using the TCD technique, we detected such hypercoagulability for the first time.",,"Sakai, K.;Nakajima, T.;Fukuhara, N.",2006,May,,0,
1530,Linear measures of temporal lobe atrophy on brain magnetic resonance imaging (MRI) but not visual rating of white matter changes can help discrimination of mild cognitive impairment (MCI) and Alzheimer's disease (AD),"Clinical discrimination of the early stages of AD and MCI is challenging. MRI indices which are simple enough to be applied by non-radiologists on hard copies would be of practical importance in the discrimination. We studied 45 consecutive patients (17 with MCI, 25 with AD, 3 with normal cognitive findings) with at least one white matter lesion (WML) on axial fluid-attenuated inversion recovery (FLAIR) MRI sequences. WML load was evaluated by Fazekas' scoring system; temporal lobe atrophy by interuncal distance (IUD) measurement. WML pattern had no significant discriminative value of AD and MCI. No significant correlation between periventricular/subcortical WML scores and neuropsychological test results was observed. The mean IUD was significantly smaller in patients with MCI compared to those with AD. The cut-off value of IUD was 28.3 mm with receiver operating curve (ROC) analysis. Area under the curve was 0.925 (95% CI: 0.800-0.983). A significant negative correlation between IUD and the mini mental state examination (MMSE), verbal fluency, clock drawing, and Rey Auditory verbal learning test (AVLT) was noted. The results indicate that measurement of IUD is a clinically useful test in discrimination of AD and MCI patients with WML(s) on brain MRI. However, severity of these lesions is not useful for distinctions.","Aged;Alzheimer Disease/ diagnosis/pathology;Area Under Curve;Atrophy;Cognition Disorders/ diagnosis/pathology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Sensitivity and Specificity;Temporal Lobe/ pathology","Saka, E.;Dogan, E. A.;Topcuoglu, M. A.;Senol, U.;Balkan, S.",2007,Mar-Apr,10.1016/j.archger.2006.04.006,0,
1531,Diffusion tensor magnetic resonance imaging for single subject diagnosis in neurodegenerative diseases,"Although magnetic resonance imaging is a standard investigation in neurodegenerative disease, sensitive and specific markers for the underlying histopathological diagnosis are largely lacking. This report presents evidence to indicate that corticobasal degeneration and progressive supranuclear palsy, in particular, might be identifiable at a single subject level with diffusion tensor imaging. Patients with clinical diagnoses of Alzheimer's disease, semantic dementia and non-fluent primary progressive aphasia (n = 9 each) were contrasted with control subjects (n = 26) with the diffusion tensor imaging measures: fractional anisotropy, axial and radial diffusivity. At 1 year follow-up, all participants with non-fluent primary progressive aphasia had evolved either corticobasal degeneration (n = 5) or progressive supranuclear palsy (n = 4). The corticobasal degeneration/progressive supranuclear palsy set showed white matter abnormalities involving the entire cerebrum. Individual maps were similar to the group level results, even in the most minimally impaired patients. Fractional anisotropy was consistently the most sensitive metric. In Alzheimer's disease and semantic dementia, by contrast, group level and individual analyses revealed limited areas of abnormality centred on the posterior cingulate and rostral temporal lobes, respectively. In both groups radial diffusivity was the most sensitive metric. Scrutiny of the standard scores for each group's most sensitive metric revealed that, although the values for every patient with corticobasal degeneration or progressive supranuclear palsy fell outside 95% of the normal mean, none of the other two groups' members had values outside this range. Further underscoring the hypothesis that this finding relates specifically to a diffuse pathological process in the white matter of the tauopathies, and is not merely a function of disease severity, a grey matter analysis consisting of group level voxel-based morphometry revealed only focal areas of atrophy in all three groups. Consistent with past reports for the respective clinical syndromes, these were centred on the left frontal operculum and caudate nucleus in non-fluent primary progressive aphasia (the corticobasal degeneration/progressive supranuclear palsy set), anterior temporal lobes in semantic dementia, and hippocampus and posterior cingulate gyrus in Alzheimer's disease. Detection of this extensive white matter lesion in corticobasal degeneration and progressive supranuclear palsy - a pathologically proven feature of these conditions - in single subjects with diffusion tensor imaging appears to have strong diagnostic marker potential for these diseases. © 2013 The Author (2013).",,"Sajjadi, S. A.;Acosta-Cabronero, J.;Patterson, K.;Diaz-De-Grenu, L. Z.;Williams, G. B.;Nestor, P. J.",2013,July,,0,
1532,"Neuroradiological findings of paretic neurosyphilis, a case report","Neuroradiological findings of a patient with paretic neurosyphilis are described. A 50-year-old male patient showed personality changes, severe dementia and some neurological deficits. Serological analysis of serum and cerebrospinal fluid demonstrated the presence of antibodies to Treponema pallidum. Computed tomography showed diffuse cerebral cortical atrophy and ventricular dilatation, and magnetic resonance (MR) imaging revealed some small abnormal signals in the white matter. Single photon emission tomography using [123I] N-isopropyl-p-iodoamphetamine (IMP-SPECT) indicated decreased activities, most markedly in the right frontal and bitemporal cortices. Although the neuroradiological findings were nonspecific, the MR imaging and IMP-SPECT findings were interesting because they have not been described previously to our knowledge.",,"Saitoh, H.;Yazaki, K.;Yoshii, F.;Shinohara, Y.",1991,Dec,,0,
1533,An autopsy case of MM2-cortical+thalamic-type sporadic Creutzfeldt-Jakob disease,"A 59-year-old Japanese man presented with depressed mood, insomnia, abnormal behavior and dementia. Visual and gait disturbance with ataxia also developed. Diffusion-weighted MRI showed widespread regions of hyperintensity in the bilateral cerebral cortex. The patient died at 62 after a progressive clinical course of 32 months. Myoclonus, periodic sharp-wave complexes on EEG, and akinetic mutism state were not observed. Neuropathologic examination showed widespread cerebral neocortical involvement with both large confluent vacuole-type, alongside fine vacuole-type spongiform changes. Mild spongiform degeneration was observed in the striatum and lateral thalamus. Severe neuron loss with hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus was present. Cerebral white matter showed diffuse myelin pallor indicating panencephalopathic-type pathology. In the cerebellar cortex, severe Purkinje neuron loss was observed, but no spongiform degeneration in the molecular layer or neuron loss in the granular cell layer. PrP immunostaining showed widespread perivacuolar-type PrP, irregular plaque-like PrP, and synaptic-type PrP depositions in the cerebral neocortex. Mild PrP deposition was observed in the striatum, lateral thalamus and brainstem, whereas PrP deposition was not apparent in the medial thalamus and inferior olivary nucleus. PrP gene analysis showed no mutations, and methionine homozygosity was observed at codon 129. Western blot analysis of protease-resistant PrP showed type 2 PrP pattern. MRI and cerebral neocortical pathology suggested MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD), whereas the clinical course and pathology of the medial thalamus and inferior olivary nucleus suggested MM2-thalamic-type sCJD. We believe this was a combination of MM2-cortical-type and MM2-thalamic-type sCJD, which explains the broad spectrum of MM2-type sCJD findings and symptoms. © 2010 Japanese Society of Neuropathology.",prion protein;adult;article;ataxia;autopsy;behavior disorder;bioaccumulation;brain degeneration;brain spongiosis;case report;cell loss;corpus striatum;Creutzfeldt Jakob disease;dementia;depression;diffusion weighted imaging;disease classification;disease course;gait disorder;histopathology;human;human tissue;immunohistochemistry;inferior olive;insomnia;male;mutational analysis;neuropathology;priority journal;Purkinje cell;thalamus;visual disorder;Western blotting,"Saito, Y.;Iwasaki, Y.;Aiba, I.;Kitamoto, T.;Yoshida, M.;Hashizume, Y.",2011,,,0,
1534,Clustering of multifocal cerebral infarctions in CADASIL: A case report,,iofetamine i 123;Notch3 receptor;adult;alopecia;blood sampling;CADASIL;case report;cognitive defect;common cold;computer assisted tomography;diffusion coefficient;diffusion weighted imaging;echocardiography;echography;electrocardiography;falling;fluid attenuated inversion recovery;gene mutation;hospital admission;human;letter;leukoencephalopathy;magnetic resonance angiography;male;Mini Mental State Examination;mood disorder;nuclear magnetic resonance imaging;priority journal;single photon emission computer tomography;whole body CT,"Saito, S.;Ozaki, A.;Takahashi, M.;Ito, H.;Matsumoto, S.;Tomimoto, H.",2011,,,0,
1535,Imaging of muscarinic acetylcholine receptors using (+)N- (11)C methyl-3-piperidyl benzilate ((11)C-3NMPB) in vascular dementia and Alzheimer's disease,"In order to clarify the integrity of muscarinic acetylcholine receptor (mAChR) in VaD and AD, PET imaging with (+) N-[(11)C]methyl-3-piperidyl benzilate ((11)C-3NMPB) was performed in 12 patients with VaD, 11 patients with AD, and 7 normal controls (NC group). The mAChR binding was compared by the ratios compared with the cerebellum which were calculated from the regions of interest (ROI), and by three-dimensional statistic analysis. Compared with the NC group, mAChR was not significantly reduced in any ROI in AD patients. In those with VaD due to cortical lesions, mAChR was reduced in the infarcted areas. On the other hand, mAChR was significantly reduced in the thalamus and anterior cingulated gyrus, but not in other cerebral cortices in patients with VaD due to subcortical lesions. Accordingly, it is suggested that the mAChR is preserved in the cerebral cortices in patients with VaD due to subcortical lesions as well as in AD patients.",,"Saito, H.",2006,Jan,,0,
1536,Comparison between PET template-based method and MRI-based method for cortical quantification of florbetapir (AV-45) uptake in vivo,"PURPOSE: Florbetapir (AV-45) has been shown to be a reliable tool for assessing in vivo amyloid load in patients with Alzheimer's disease from the early stages. However, nonspecific white matter binding has been reported in healthy subjects as well as in patients with Alzheimer's disease. To avoid this issue, cortical quantification might increase the reliability of AV-45 PET analyses. In this study, we compared two quantification methods for AV-45 binding, a classical method relying on PET template registration (route 1), and a MRI-based method (route 2) for cortical quantification. METHODS: We recruited 22 patients at the prodromal stage of Alzheimer's disease and 17 matched controls. AV-45 binding was assessed using both methods, and target-to-cerebellum mean global standard uptake values (SUVr) were obtained for each of them, together with SUVr in specific regions of interest. Quantification using the two routes was compared between the clinical groups (intragroup comparison), and between groups for each route (intergroup comparison). Discriminant analysis was performed. RESULTS: In the intragroup comparison, differences in uptake values were observed between route 1 and route 2 in both groups. In the intergroup comparison, AV-45 uptake was higher in patients than controls in all regions of interest using both methods, but the effect size of this difference was larger using route 2. In the discriminant analysis, route 2 showed a higher specificity (94.1 % versus 70.6 %), despite a lower sensitivity (77.3 % versus 86.4 %), and D-prime values were higher for route 2. CONCLUSION: These findings suggest that, although both quantification methods enabled patients at early stages of Alzheimer's disease to be well discriminated from controls, PET template-based quantification seems adequate for clinical use, while the MRI-based cortical quantification method led to greater intergroup differences and may be more suitable for use in current clinical research.","Aged;Alzheimer Disease/diagnosis/*radionuclide imaging;*Aniline Compounds;Case-Control Studies;Cerebral Cortex/radionuclide imaging;*Ethylene Glycols;Female;Humans;Image Processing, Computer-Assisted/*methods;*Magnetic Resonance Imaging;Male;*Positron-Emission Tomography;*Radiopharmaceuticals","Saint-Aubert, L.;Nemmi, F.;Peran, P.;Barbeau, E. J.;Payoux, P.;Chollet, F.;Pariente, J.",2014,May,10.1007/s00259-013-2656-8,0,
1537,Computer tomography for prediction of cognitive outcomes after ischemic cerebrovascular events,"BACKGROUND: The aim of this study was to evaluate whether parameters noted on a single, acute computed tomographic (CT) scan, are associated with significant cognitive impairment (SCogI), and can help in the prediction of SCogI 3-6 months after stroke or transient ischemic attack (TIA). METHODS: Patients with a recent (</=14 days) ischemic stroke or TIA, without preexisting dementia, underwent noncontrast CT scan within 24 hours of admission. A formal neuropsychologic battery was administered 3-6 months from index stroke. SCogI was defined as moderate cognitively impaired, not demented (CIND) (>/=3 domains impaired), and dementia diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Logistic regression models were used to examine associations between CT parameters and SCogI. Receiver operating characteristic analysis with an area under the curve (AUC) was performed to assess discriminatory ability of radiological parameters for SCogI. RESULTS: In all, 318 patients were included: 250 (78.6 %) with ischemic stroke and 68 (21.4%) with TIA; the mean age was 59.8 (+/-11.4) years. At 3-6 months, 76 (23.9 %) had SCogI (67 CIND moderate and 9 dementia). The presence of significant atrophy (P = .02) and chronic infarcts (P = .03) were associated with SCogI at 3-6 months. A significant increase in AUC was noted after addition of summarized CT results to a clinical score derived from age and baseline Montreal Cognitive Assessment (cutoff 21 of 22) for detection of SCogI: .83 (.78-.89) to .86 (.82-.91); P = .03. CONCLUSIONS: CT parameters are independently associated with SCogI at 3-6 months after an ischemic cerebrovascular event and may be a clinically useful component in predicting for SCogI after stroke.","Aged;Brain Ischemia/*diagnosis/*psychology;Cognition Disorders/*etiology/*psychology;Disability Evaluation;Female;Follow-Up Studies;Humans;Ischemic Attack, Transient/diagnosis;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Stroke/diagnosis;Tomography, X-Ray Computed/*methods;Treatment Outcome;Stroke;cognitive impairment;dementia;transient ischemic attack","Saini, M.;Tan, C. S.;Hilal, S.;Dong, Y.;Ting, E.;Ikram, M. K.;Sharma, V. K.;Venketasubramanian, N.;Chen, C.",2014,Aug,10.1016/j.jstrokecerebrovasdis.2014.02.007,0,
1538,Prevalence and Risk Factors of Acute Incidental Infarcts,"BACKGROUND AND PURPOSE: The study of silent stroke has been limited to imaging of chronic infarcts; acute incidental infarcts (AII) detected on brain magnetic resonance imaging have been less investigated. This study aims to describe prevalence and risk factors of AII in a community and a clinic-based population. METHODS: Subjects were drawn from 2 ongoing studies: Epidemiology of Dementia in Singapore study, which is a subsample from a population-based study, and a clinic-based case-control study. Subjects from both studies underwent similar clinical and neuropsychological assessments and brain magnetic resonance imaging. Prevalence of AII from these studies was determined. Subsequently, risk factors of AII were examined using multivariable logistic regression models. RESULTS: AII were seen in 7 of 623 (1.2%) subjects in Epidemiology of Dementia in Singapore (mean age, 70.9+/-6.8 years; 45% men) and in 12 of 389 (3.2%) subjects (mean age, 72.1+/-8.3 years; 46% men) in the clinic-based study. AII were present in 0.8% of subjects with no cognitive impairment, 1.9% of those with cognitive impairment not dementia, and 4.2% of subjects with dementia. Significant association of AII was found with cerebral microbleeds (>/=5) in the Epidemiology of Dementia in Singapore (odds ratio, 6.76; 95% confidence interval, 1.28-35.65; P=0.02) and in the clinic-based cohort (odds ratio, 4.65; 95% confidence interval, 1.39-15.53; P=0.01). There was no association of AII with hypertension, diabetes mellitus, or hyperlipidemia. CONCLUSIONS: AII are more likely to be present in those with cognitive impairment. Although a cause-effect relationship between the presence of AII and cognitive impairment is plausible, the association may be because of under-reporting of symptoms by individuals with cognitive impairment. The association between AII and cerebral microbleeds may indicate cerebral vasculopathy, independent of traditional vascular risk factors.","Aged;Aged, 80 and over;Brain Infarction/complications/ epidemiology;Case-Control Studies;Cognition Disorders/complications;Female;Humans;Incidental Findings;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prevalence;Risk Factors","Saini, M.;Suministrado, M. S.;Hilal, S.;Dong, Y. H.;Venketasubramanian, N.;Ikram, M. K.;Chen, C.",2015,Oct,10.1161/strokeaha.115.009963,0,
1539,Silent stroke: not listened to rather than silent,"BACKGROUND AND PURPOSE: The prevalence of silent brain infarcts varies from 8% to 28% in the general elderly population. Silent brain infarcts are associated with increased risk of subsequent stroke and cognitive dysfunction. By definition, silent strokes lack clinically overt stroke-like symptoms and fail to come to clinical attention; however, impaired recall of symptoms may be a potential confounder. Our aim is to report a series of patients with incidentally detected acute and subacute strokes and examine whether they were truly asymptomatic. METHODS: Subjects included in this study were drawn from ongoing dementia research studies at the Memory Ageing and Cognition Center, in which all participants underwent a cranial MRI. Incidental hyperintense lesions on diffusion-weighted imaging with corresponding apparent diffusion coefficient defects indicative of acute/subacute silent stroke were identified. Clinical data for individuals with incidental hyperintense lesions on diffusion-weighted imaging were collated. RESULTS: Six of 649 subjects had incidental hyperintense lesions on diffusion-weighted imaging; on retrospective questioning, 3 recalled symptoms temporally correlated with MRI lesions, which had been reported to but ignored by family members. Two subjects had focal neurological signs. A majority of the subjects with incidental hyperintense lesions on diffusion-weighted imaging had significant cognitive impairment. CONCLUSIONS: A significant number of strokes may be ""silent"" due to lack of awareness of stroke-like symptoms in the elderly and their families. Enhanced stroke prevention education strategies are needed for the elderly population and, in particular, for their families.","Aged;Aged, 80 and over;Brain/ pathology;Cognition Disorders/ etiology/pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Incidental Findings;Male;Stroke/ complications/ pathology","Saini, M.;Ikram, K.;Hilal, S.;Qiu, A.;Venketasubramanian, N.;Chen, C.",2012,Nov,10.1161/strokeaha.112.666461,0,
1540,Evidence of reduced glutamate in the frontal lobe of HIV-seropositive patients,"Neurological complications associated with the acquired immunodeficiency syndrome, in particular, HIV-associated dementia, continue to plague those infected. We report our finding that the concentration of brain Glu is reduced in the frontal white matter region in this condition. In addition, our data appear to absolve highly active retroviral therapy (HAART) from blame, as drug-naive patients were equally affected. Our findings suggest that Glu neurotransmission is abnormal and may be a key target for early interventions to reduce the later incidence of neurocognitive impairment and dementia among HIV-seropositive patients.",Adult;Aspartic Acid/analogs & derivatives/metabolism;Case-Control Studies;Female;Frontal Lobe/*metabolism/*virology;Glutamic Acid/*metabolism;HIV Seropositivity/*metabolism;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Sailasuta, N.;Shriner, K.;Ross, B.",2009,Apr,10.1002/nbm.1329,0,
1541,Neuronal-Glia Markers by Magnetic Resonance Spectroscopy in HIV before and after Combination Antiretroviral Therapy,"Objective: Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. Methods: We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n 59, 27 with HAND) and after 12 months of cART. Results: At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P 0.002) and in the posterior cingulate gyrus (PCG, P 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P 0.040). N-acetylaspartate was elevated in the BG (P 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P 0.031), decreased creatine in PCG (P 0.026) and increased MI in frontal gray matter (FGM, P 0.023). At 12 months, we observed an increase in BG MI (P 0.038) and in FGM (P 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P 0.018) and decreased glutamate in both FWM (P 0.027) and BG (P 0.013). Conclusions: cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.",,"Sailasuta, N.;Ananworanich, J.;Lerdlum, S.;Sithinamsuwan, P.;Fletcher, J. L. K.;Tipsuk, S.;Pothisri, M.;Jadwattanakul, T.;Jirajariyavej, S.;Chalermchai, T.;Catella, S.;Busovaca, E.;Desai, A.;Paul, R.;Valcour, V.;Chaisit, P.;Chinvarun, Y.;Thongkramjaroen, P.;Thongmuang, S.;Jarupittaya, S.;Khongtia, P.;Methajittiphun, P.;Mingkwanrungruang, P.;Phanuphak, N.;Kroon, E.;Terratakulpisarn, N.;Chomchey, N.;Suttichom, D.;Rattanamanee, S.;Boonchan, M.;Kanaprach, R.;Mun, E.;Hutchings, N.;Clifford, K.;Wendelken, L.",2016,1,,0,
1542,Clasmatodendrosis correlating with periventricular hyperintensity in mixed dementia,"We report a 79-year-old woman with possible Alzheimer's disease and confluent periventricular white matter hyperintensities on magnetic resonance imaging in whom postmortem analysis unexpectedly demonstrated no periventricular demyelination or cerebral arteriosclerosis. However, astrocytes in the periventricular white matter exhibited clasmatodendrosis, defined as cytoplasmic swelling and vacuolation of astroglia, with beading of their dendrites. This finding represents a previously unrecognized correlate of periventricular white matter hyperintensities.",,"Sahlas, D. J.;Bilbao, J. M.;Swartz, R. H.;Black, S. E.",2002,September,,0,
1543,Positron Emission Tomographic Imaging in Stroke: Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke,"BACKGROUND AND PURPOSE: Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of beta-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger beta-amyloid deposition, with deposition over time. METHODS: Patients were recruited within 40 days of acute ischemic stroke and imaged with computed tomographic or magnetic resonance imaging and Pittsburgh compound B (11C-PiB) positron emission tomographic scans. Follow-up positron emission tomographic scanning was performed in a subgroup </=18 months after the stroke event. Standardized uptake value ratios for regions of interest were analyzed after coregistration. RESULTS: Forty-seven patients were imaged with (11)C-PiB positron emission tomography. There was an increase in (11)C-PiB accumulation in the stroke area compared with a reference region in the contralesional hemisphere, which was not statistically significant (median difference in standardized uptake value ratio, 0.07 [95% confidence interval, -0.06 to 0.123]; P=0.452). There was no significant increase in the accumulation of (11)C-PiB in the peri-infarct region or in the ipsilesional hemisphere (median difference in standardized uptake value ratio, 0.04 [95% confidence interval, -0.02 to 0.10]; P=0.095). We repeated (11)C-PiB positron emission tomography in 21 patients and found a significant reduction in accumulation of (11)C-PiB between regions of interest (median difference in standardized uptake value ratio, -0.08 [95% confidence interval, -0.23 to -0.03]; P=0.04). CONCLUSIONS: There was no significant increase in (11)C-PiB accumulation in or around the infarct. There was no increase in ipsilesional hemispheric (11)C-PiB accumulation over time. We found no evidence that infarction leads to sustained or increased beta-amyloid deposition </=18 months after stroke.",,"Sahathevan, R.;Linden, T.;Villemagne, V. L.;Churilov, L.;Ly, J. V.;Rowe, C.;Donnan, G.;Brodtmann, A.",2016,Jan,10.1161/strokeaha.115.010528,0,
1544,Age-related decline in white matter integrity in a mouse model of tauopathy: an in vivo diffusion tensor magnetic resonance imaging study,"Elevated expression of human hyperphosphorylated tau is associated with neuronal loss and white matter (WM) pathology in Alzheimer's disease (AD) and related neurodegenerative disorders. Using in vivo diffusion tensor magnetic resonance imaging (DT-MRI) at 11.1 Tesla we measured age-related alterations in WM diffusion anisotropy indices in a mouse model of human tauopathy (rTg4510) and nontransgenic (nonTg) control mice at the age of 2.5, 4.5, and 8 months. Similar to previous DT-MRI studies in AD subjects, 8-month-old rTg4510 mice showed lower fractional anisotropy (FA) values in WM structures than nonTg. The low WM FA in rTg4510 mice was observed in the genu and splenium of the corpus callosum, anterior commissure, fimbria, and internal capsule and was associated with a higher radial diffusivity than nonTg. Interestingly, rTg4510 mice showed lower estimates for the mode of anisotropy than controls at 2.5 months suggesting that changes in this diffusivity metric are detectable at an early stage preceding severe tauopathy. Immunogold electron microscopy partly supports our diffusion tensor imaging findings. At the age of 4 months, rTg4510 mice show axonal tau inclusions and unmyelinated processes. At later ages (12 months and 14 months) we observed inclusions in myelin sheath, axons, and unmyelinated processes, and a ""disorganized"" pattern of myelinated fiber arrangement with enlarged inter-axonal spaces in rTg4510 but not in nonTg mice. Our data support a role for the progression of tau pathology in reduced WM integrity measured by DT-MRI. Further in vivo DT-MRI studies in the rTg4510 mouse should help better discern the detailed mechanisms of reduced FA and anisotropy mode, and the specific role of tau during neurodegeneration.","Aging/metabolism/ pathology;Alzheimer Disease/metabolism/pathology;Animals;Anisotropy;Corpus Callosum/metabolism/ pathology;Diffusion Tensor Imaging/ methods;Disease Models, Animal;Mice;Mice, Transgenic;Neurodegenerative Diseases/metabolism/pathology;Tauopathies/metabolism/ pathology;tau Proteins/metabolism","Sahara, N.;Perez, P. D.;Lin, W. L.;Dickson, D. W.;Ren, Y.;Zeng, H.;Lewis, J.;Febo, M.",2014,Jun,10.1016/j.neurobiolaging.2013.12.009,0,
1545,Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia,"Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkBalpha-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.",Astrocytes;Diffusion tensor imaging (DTI);Glia;NF-kB;Neuroinflammation;vascular cognitive impairment,"Saggu, R.;Schumacher, T.;Gerich, F.;Rakers, C.;Tai, K.;Delekate, A.;Petzold, G. C.",2016,,10.1186/s40478-016-0350-3,0,
1546,MRI finding in an offspring of an individual with familial Alzheimer's disease,An at risk offspring of an individual with familial Alzheimer's disease showed a white matter lesion on magnetic resonance imaging. This finding might appear in some individuals with Alzheimer's disease before its clinical onset.,,"Sagawa, K.;Kawakatsu, S.;Totsuka, S.",1992,1992,,0,
1547,Cerebral amyloid angiopathy-associated microbleed mimicking transient ischemic attack,,acetylsalicylic acid;amyloid beta protein;hydroxymethylglutaryl coenzyme A reductase inhibitor;aged;Alzheimer disease;ataxic aphasia;autopsy;brain hemorrhage;case report;computer assisted tomography;differential diagnosis;diffusion weighted imaging;disease association;Doppler echography;dyslipidemia;human;laboratory test;left hemisphere;letter;lumbar puncture;male;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;systemic vasculitis;transesophageal echocardiography;transient ischemic attack;transthoracic echocardiography;vascular amyloidosis;white matter lesion;aspirin,"Safouris, A.;Gazagnes, M. D.;Triantafyllou, N.;Tsivgoulis, G.",2015,,,0,
1548,CADASIL: Hereditary vascular dementia. Description of an apparently sporadic clinical case,"We describe a patient with CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), the first of four patients diagnosed in our service since 1998, correlating clinical, imaging, and muscular pathology (on electronic microscopy) data. The patient is a woman with no risk factors for cerebrovascular pathology who suffered two transient ischemic attacks at the age of 29. Seven years later, she developed symptoms of depression manifested as psychomotor withdrawal and progressive Parkinsonism that did not respond to pharmacological treatment. An MRI brain scan showed extensive bilateral alterations in the white matter in the frontal and occipital regions, hyperintense in T2 and hypointense in T1-weighted images, without gadolinium enhancement. They had no mass effect, were associated with leukoaraiosis, and were compatible with the diagnosis of CADASIL. Muscle biopsy showed an arteriopathy with CADASIL-type osmiophilic granular deposits in the blood vessels. No history of symptomatic dementia or cerebrovascular disorders were found among the patient's mother, father, aunts, uncles, or grandparents. This is most likely a sporadic case. No genetic studies or biopsies were done in asymptomatic relatives. © 2006 Sociedad de Neurología, Psiquiatría y Neurocirugía.",,"Sáez, D.;Trujillo, O.;Nogales-Gaete, J.;Figueroa, T.;Valenzuela, D.",2003,Jan,,0,
1549,Diabetes mellitus and cognitive impairments,"There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer's disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings.",amyloid beta protein;antidiabetic agent;glucose;hemoglobin A1c;insulin;insulin receptor;Alzheimer disease;amnesia;cardiovascular risk;chronic inflammation;cognitive defect;comorbidity;declarative memory;dementia;diabetes mellitus;diabetic retinopathy;diagnostic imaging;diffusion tensor imaging;disease association;dyslipidemia;glucose blood level;glycemic control;heredity;human;hypertension;hypoglycemia;insulin dependent diabetes mellitus;longitudinal study;Mini Mental State Examination;multiinfarct dementia;neuropsychological test;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;pathogenesis;prevalence;recall;risk factor;short survey;working memory,"Saedi, E.;Gheini, M. R.;Faiz, F.;Arami, M. A.",2016,,10.4239/wjd.v7.i17.412,0,
1550,Cerebral infarcts and cognitive performance: importance of location and number of infarcts,"BACKGROUND AND PURPOSE: Cerebral infarcts increase the risk for cognitive impairment. The relevance of location and number of infarcts with respect to cognitive function is less clear. METHODS: We studied the cross-sectional association between number and location of infarcts and cognitive performance in 4030 nondemented participants of the Age Gene/Environment Susceptibility-Reykjavik Study. Composite scores for memory, processing speed, and executive function were created from a neuropsychological battery. Subcortical, cortical, and cerebellar infarcts were identified on brain MRI. We performed linear regression analyses adjusted for demographic and vascular risk factors, depression, white matter lesions, and atrophy. RESULTS: Compared to participants with no infarcts, those with infarcts in multiple locations (n=287, 7%) had slower processing speed (beta=-0.19; P<0.001) and poorer memory (beta=-0.16; P<0.001) and executive function (beta=-0.12; P=0.003). Compared to no infarcts, the presence of either subcortical infarcts only (n=275; beta=-0.12; P=0.016) or cortical infarcts only (n=215; beta=-0.17; P=0.001) was associated with poorer memory performance. Compared to no infarcts, a combination of cortical and subcortical infarcts (n=45) was associated with slower processing speed (beta=-0.38; P<0.001) and poorer executive function (beta=-0.22; P=0.02), whereas a combination of cerebellar and subcortical infarcts (n=89) was associated with slower processing speed (beta=-0.15; P=0.04). Infarcts in all 3 locations was associated with slower processing speed (beta=-0.33; P=0.002). CONCLUSIONS: Having infarcts in >1 location is associated with poor performance in memory, processing speed, and executive function, independent of cardiovascular comorbidities, white matter lesions, and brain atrophy, suggesting that both the number and the distribution of infarcts jointly contribute to cognitive impairment.",Aged;Cardiovascular Diseases/epidemiology;Cerebral Infarction/genetics/*pathology/*psychology;Cognition Disorders/genetics/*pathology/*psychology;Dementia/diagnosis/psychology;Female;Humans;Iceland/epidemiology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Risk Factors,"Saczynski, J. S.;Sigurdsson, S.;Jonsdottir, M. K.;Eiriksdottir, G.;Jonsson, P. V.;Garcia, M. E.;Kjartansson, O.;Lopez, O.;van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2009,Mar,10.1161/strokeaha.108.530212,0,
1551,Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study,"OBJECTIVE: To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS: This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose > or =7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6-6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS: After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 and 25.7 vs. 25.3%, P < 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14-1.85]) or multiple (2.27 [1.60-3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all P(trend) < 0.05), and a greater likelihood of single and multiple cerebral infarcts (all P(trend) < 0.01). CONCLUSIONS: Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain.","Age Factors;Aged;Aged, 80 and over;Brain Injuries/ epidemiology/pathology;Cerebral Infarction/epidemiology/pathology;Diabetes Mellitus, Type 2/ epidemiology/pathology;Disease Susceptibility;Female;Humans;Male;Sex Factors","Saczynski, J. S.;Siggurdsson, S.;Jonsson, P. V.;Eiriksdottir, G.;Olafsdottir, E.;Kjartansson, O.;Harris, T. B.;van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2009,Sep,10.2337/dc08-2300,0,
1552,A multicenter study of two magnetic resonance spectroscopy techniques in individuals with HIV dementia,"PURPOSE: To evaluate single-voxel proton magnetic resonance spectroscopy (SV-MRS) and magnetic resonance spectroscopic imaging (MRSI) metabolite results in individuals with HIV dementia. MATERIALS AND METHODS: Twenty HIV-positive (HIV+) individuals underwent SV-MRS (TE 35 msec) and MRSI (TE 280 msec). Results were stratified according to serostatus, dementia severity, psychomotor speed performance, and functional impairment. RESULTS: HIV+ individuals with psychomotor slowing had an increased myoinositol/creatine (mI/Cr) ratio (0.63 vs. 0.45) in the frontal white matter using SV-MRS and an increased choline (Cho)/Cr ratio (1.88 vs. 1.41) in the mesial frontal gray matter using MRSI compared to HIV+ individuals without psychomotor slowing. Using MRSI, subjects with HIV dementia also had a decreased N-acetyl aspartate (NAA)/Cho ratio (1.55 vs. 2.53) compared to HIV+ individuals without cognitive impairment in the mesial frontal gray matter. Both techniques detected metabolite ratio abnormalities associated with abnormal functional performance. CONCLUSION: SV-MRS and MRSI offer complementary roles in evaluating individuals with HIV dementia. Short TE SV-MRS measures mI, which may be elevated in early HIV dementia, whereas MRSI provides wider spatial coverage to examine specific regional changes.",AIDS Dementia Complex/ diagnosis;Adult;Brain Chemistry;Creatinine/analysis;Female;Humans;Inositol/analysis;Magnetic Resonance Spectroscopy/ methods;Male,"Sacktor, N.;Skolasky, R. L.;Ernst, T.;Mao, X.;Selnes, O.;Pomper, M. G.;Chang, L.;Zhong, K.;Shungu, D. C.;Marder, K.;Shibata, D.;Schifitto, G.;Bobo, L.;Barker, P. B.",2005,Apr,10.1002/jmri.20272,0,
1553,Homocysteine as a risk factor for cognitive impairment in stroke patients,"Background: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment. Methods: We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B12, creatinine and plasma fibrinogen levels were obtained. Results: tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B12 and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T2-weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-to-brain ratios as measures of brain atrophy. Conclusion: This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment. Copyright © 2003 S. Karger AG, Basel.",creatinine;cyanocobalamin;fibrinogen;folic acid;homocysteine;adult;age;aged;article;attention;brain atrophy;brain function;brain scintiscanning;cognitive defect;controlled study;correlation analysis;creatinine blood level;female;fibrinogen blood level;folic acid blood level;heart stroke volume;human;major clinical study;male;neuropsychological test;neuropsychology;nuclear magnetic resonance imaging;principal component analysis;priority journal;risk factor;cerebrovascular accident;vitamin blood level;white matter,"Sachdev, P. S.;Valenzuela, M. J.;Brodaty, H.;Wang, X. L.;Looi, J.;Lorentz, L.;Howard, L.;Jones, M.;Zagami, A. S.;Gillies, D.;Wilcken, D. E. L.",2003,,,0,
1554,Progression of cognitive impairment in stroke/TIA patients over 3 years,"OBJECTIVES: To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). METHODS: A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. RESULTS: Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE epsilon4 allele had greater global cognitive and verbal memory decline. CONCLUSIONS: In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE epsilon4 was a risk factor in those without a subsequent stroke/TIA.","Aged;Aged, 80 and over;Apolipoproteins E/genetics;Brain/pathology;Cardiovascular Diseases/etiology;Case-Control Studies;Cognition Disorders/*etiology/pathology;Dementia/etiology/pathology;Disease Progression;Female;Humans;Ischemic Attack, Transient/*complications;Magnetic Resonance Imaging;Male;Middle Aged;Neuroimaging;Neuropsychological Tests;Risk Factors;Stroke/*complications;Time Factors;Mri;cognitive decline;prognosis;stroke;transient ischemic attack","Sachdev, P. S.;Lipnicki, D. M.;Crawford, J. D.;Wen, W.;Brodaty, H.",2014,Dec,10.1136/jnnp-2013-306776,0,
1555,The contribution of twins to the study of cognitive ageing and dementia: The Older Australian Twins Study,"The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1",,"Sachdev, P. S.;Lee, T.;Wen, W.;Ames, D.;Batouli, A. H.;Bowden, J.;Brodaty, H.;Chong, E.;Crawford, J.;Kang, K.;Mather, K.;Lammel, A.;Slavin, M. J.;Thalamuthu, A.;Trollor, J.;Wright, M. J.",2013,December,,0,
1556,Hippocampal size and dementia in stroke patients: the Sydney stroke study,"BACKGROUND: Hippocampal atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippocampal size can help differentiate the two disorders. METHODS: We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippocampus and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. RESULTS: Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippocampus size and gray and white matter volumes were not different. WMHs and amygdala but not hippocampal volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippocampus volume significantly correlated with new visual learning. CONCLUSIONS: Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippocampal atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippocampus volume relates to episodic memory, especially right hippocampus and new visual learning. A longitudinal study of these subjects will determine whether hippocampal atrophy is a late development in VaD.","Aged;Alzheimer Disease/complications/pathology/physiopathology;Amygdala/pathology/physiopathology;Atrophy/etiology/*pathology/physiopathology;Dementia, Vascular/complications/*pathology/physiopathology;Diagnosis, Differential;Diffusion Magnetic Resonance Imaging;Female;Hippocampus/*pathology/physiopathology;Humans;Lateral Ventricles/pathology;Magnetic Resonance Imaging;Male;Memory Disorders/etiology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;New South Wales;Predictive Value of Tests;Stroke/complications/*pathology/physiopathology","Sachdev, P. S.;Chen, X.;Joscelyne, A.;Wen, W.;Altendorf, A.;Brodaty, H.",2007,Sep 15,10.1016/j.jns.2007.04.006,0,
1557,The determinants and longitudinal course of post-stroke mild cognitive impairment,"While post-stroke dementia has been extensively investigated, the large number of patients with mild cognitive impairment (MCI) following stroke has received less attention, and reports on the longitudinal course of such impairment are inconsistent in their findings. We examined patients with MCI (n = 45) or no cognitive impairment (NCI) (n = 59), based on consensus criteria following detailed neuropsychological assessments and magnetic resonance imaging (MRI) scans, and compared them with healthy control subjects (n = 84), all of whom were assessed at two time points, 3 years apart. The MCI at baseline in this group was judged to be vascular in etiology (vaMCI). Incident dementia was diagnosed in 24.4% of vaMCI and 8.5% of NCI subjects and no control subjects over 3 years, giving a rate of conversion of approximately 8% per year in post-stroke vaMCI. The vaMCI group showed greater decline in logical memory than the NCI group. Within the vaMCI group, those who developed dementia had great decline in language and executive function. Compared with NCI patients, those with vaMCI had more vascular risk factors and more white matter hyperintensities on MRI at baseline, but did not differ in their brain or hippocampal volumes. Neither MRI volumetric measures nor interval cerebrovascular events predicted decline in function. The major determinant of decline and categorical transition was impaired performance at baseline, suggesting that those with mild impairment post-stroke are more vulnerable to subsequent decline.",Activities of Daily Living;Aged;Analysis of Variance;Cognition Disorders/ diagnosis/ etiology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Severity of Illness Index;Stroke/ complications;Time Factors,"Sachdev, P. S.;Chen, X.;Brodaty, H.;Thompson, C.;Altendorf, A.;Wen, W.",2009,Nov,10.1017/s1355617709990579,0,
1558,The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients,"OBJECTIVE: To characterize the neuropsychological profile of vascular cognitive impairment (VCI) and vascular dementia (VaD). METHODS: The authors examined 170 patients with stroke or TIA at 3 to 6 months after the vascular event, and 96 age-matched healthy controls, with detailed neuropsychological and medical-psychiatric assessments, with a majority (66.7%) undergoing MRI brain scans. The subjects were diagnosed as having VaD, VCI, or no cognitive impairment by consensus. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. RESULTS: VaD subjects had disturbance in all cognitive domains, with verbal memory, especially retention, being less affected. VCI subjects had similar but less severe disturbance. The domains that best discriminated cognitively impaired from unimpaired patients were abstraction, mental flexibility, information processing speed, and working memory. Cognitive impairment had a significant correlation with deep white matter hyperintensities, but not with volume and number of infarctions, even though the VaD subjects had larger infarct volumes than VCI subjects. The MRI variables did not provide additional discrimination between subgroups. CONCLUSIONS: The cognitive deficits in VaD and VCI are characterized by disturbance of frontal functions, with less verbal memory impairment. VaD and VCI differ in severity but not pattern of disturbance. The brain lesions that best account for these deficits are noninfarct subcortical white matter and gray matter changes due to ischemia. The picture of VaD/VCI presented shows subcortical deficits embellished by cognitive deficits from cortical infarctions.","Aged;Brain/blood supply/pathology;Cognition Disorders/*diagnosis/epidemiology;Comorbidity;Dementia, Vascular/*diagnosis/epidemiology;Discriminant Analysis;Female;Hospitals, Teaching/statistics & numerical data;Humans;Ischemic Attack, Transient/epidemiology/*physiopathology;Magnetic Resonance Imaging/statistics & numerical data;Male;Neuropsychological Tests/*statistics & numerical data;New South Wales/epidemiology;Predictive Value of Tests;Psychomotor Disorders/diagnosis/epidemiology;Stroke/epidemiology/*physiopathology","Sachdev, P. S.;Brodaty, H.;Valenzuela, M. J.;Lorentz, L.;Looi, J. C.;Wen, W.;Zagami, A. S.",2004,Mar 23,,0,
1559,Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study,"BACKGROUND: Dementia following stroke is common but its determinants are still incompletely understood. METHODS: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50-85 years, 3-6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. RESULTS: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50-59 years, 24% in those aged 60-69 years and 23% in those 70-79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. CONCLUSION: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.",Aged;Australia/epidemiology;Brain/blood supply/pathology;Brain Ischemia/*complications/*epidemiology/pathology;Catchment Area (Health);Cerebrovascular Circulation/physiology;Cognition Disorders/diagnosis/*epidemiology/*etiology;Dementia/diagnosis/*epidemiology/*etiology;Female;Health Status;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prevalence;Risk Factors;Severity of Illness Index,"Sachdev, P. S.;Brodaty, H.;Valenzuela, M. J.;Lorentz, L.;Looi, J. C.;Berman, K.;Ross, A.;Wen, W.;Zagami, A. S.",2006,,10.1159/000091434,0,
1560,"Pulmonary function, cognitive impairment and brain atrophy in a middle-aged community sample","Objective: To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. Methods: A random sub-sample of 469 persons (men = 252) aged 60-64 years from a larger community sample underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV(1)). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippocampal volume, and white matter hyperintensity (WMH) volume. Results: FEV(1) had a significant negative correlation with overall brain atrophy and VBR in men. The FEV(1)/FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV(1) and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. Conclusions: Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men. Copyright © 2006 S. Karger AG.",,"Sachdev, P. S.;Anstey, K. J.;Parslow, R. A.;Wen, W.;Maller, J.;Kumar, R.;Christensen, H.;Jorm, A. F.",2006,May,,0,
1561,Should we distinguish between periventricular and deep white matter hyperintensities? [4] (multiple letters),,brain atrophy;brain perfusion;brain region;dementia;human;letter;neuroimaging;nuclear magnetic resonance imaging;priority journal;white matter,"Sachdev, P.;Wen, W.;DeCarli, C.;Harvey, D.",2005,,,0,
1562,Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men,"BACKGROUND: High serum homocysteine (HCY) levels have been associated with thromboembolic cerebrovascular disease, but their relationship to microvascular disease is uncertain. Homocysteine also has a direct neurotoxic effect and has been linked to brain atrophy and an increased risk of Alzheimer disease. OBJECTIVE: To examine the relationship of HCY levels to brain and cognitive measures in a healthy community sample. DESIGN: Cross-sectional study. SETTING: Individuals residing in Canberra and Queanbeyan, Australia, who were participating in the longitudinal PATH Through Life Project. PARTICIPANTS: Individuals aged 60 to 64 years selected randomly from the community, 196 men and 189 women. MAIN OUTCOME MEASURES: Regression coefficients with HCY level as the putative determinant and various magnetic resonance imaging measures (brain atrophy index, ventricle-brain ratios, volume of periventricular and deep white matter hyperintensities) and cognitive measures (information processing speed, verbal memory, fine motor speed) as dependent measures. RESULTS: Homocysteine levels did not have a significant relationship with brain atrophy index or ventricle-brain ratios. High HCY levels were related to increased deep white matter hyperintensities but not periventricular white matter hyperintensities, after correcting for levels of folate, vitamin B(12), creatinine, and thyrotropin; hypertension; smoking; and diabetes, the relationship being significant only in men. Homocysteine levels were related to impairment in verbal memory and fine motor speed but not after the previously mentioned correction. CONCLUSIONS: Total HCY level is independently related to leukoaraiosis in middle-aged men, and this may be functionally relevant in the form of mild cognitive impairment. The remediation of hyperhomocysteinemia should begin early in life if its deleterious effects on the brain are to be prevented.","Brain/ pathology/physiology/radiography;Brain Diseases/ blood/pathology/radiography;Cognition/ physiology;Cross-Sectional Studies;Female;Homocysteine/ blood;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Regression Analysis;Sex Factors","Sachdev, P.;Parslow, R.;Salonikas, C.;Lux, O.;Wen, W.;Kumar, R.;Naidoo, D.;Christensen, H.;Jorm, A.",2004,Sep,10.1001/archneur.61.9.1369,0,
1563,Reliability and validity of ratings of signal hyperintensities on MRI by visual inspection and computerised measurement,"Brain magnetic resonance imaging (MRI) scans on 98 elderly subjects, 62 with a diagnosis of schizophrenia and 36 healthy controls, were independently and blindly rated by two investigators using the visual rating methods of Fazekas et al. (Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Neuroradiology 8, 421-426) and Victoroff et al. (Victoroff, J., Mack, W.J., Grafton, S.T., Schreiber, S.S., Chui, H.C., 1994. A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 44, 2267-2276) for periventricular, deep white matter and subcortical gray matter signal hyperintensities (SHs) on T2-weighted images. The hyperintense signal volumes were measured by manual delineation of the signals on a workstation using Analyze software (computerised method). The subjects also underwent a detailed neuropsychological assessment. There was a high correlation between two experienced raters for both visual ratings, and the correspondence between the two methods was high. The inter-rater reliability for the computerised method was modest but significant, and the association between the visual and computerised methods was good except for ratings for SHs in subcortical nuclei. The Fazekas and computerised methods, and to a lesser degree the Victoroff method, had modest but significant correlations with some neuropsychological test measures. In conclusion, we did not demonstrate a clear superiority in reliability or validity for one demanding computerised method of rating SHs. Visual ratings should therefore be considered adequate for most clinical and research purposes, but such ratings should be accompanied by adequate training and the provision of standard reference images.","Aged;Brain/abnormalities/ pathology;Diagnosis, Computer-Assisted;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Reproducibility of Results;Schizophrenia/ diagnosis;Severity of Illness Index","Sachdev, P.;Cathcart, S.;Shnier, R.;Wen, W.;Brodaty, H.",1999,Dec 20,,0,
1564,"Homocysteine, cerebrovascular disease and brain atrophy","Homocysteine (Hcy) is known to increase the risk of cerebrovascular disease (CVD). Recent evidence suggests its direct contribution to brain atrophy, cognitive impairment and possibly Alzheimer disease (AD). This paper reports the results of two studies of the impact of Hcy on the brain. In the Sydney Stroke Study (N=131 stroke patients, 81 healthy controls), higher Hcy levels were related to increased number of strokes and greater cognitive impairment, in particular, frontal-executive function and attention. In the control group, Hcy was related to increased subcortical atrophy. In the PATH Through Life Study, involving 60-64 years old community-dwelling individuals (N=385), Hcy was related to an increase in white matter hyperintensities, as well as impairment in verbal memory and fine motor speed. Hcy increases the risk of micro- and macrovascular disease as well as brain atrophy, and thereby impaired cognition. Remediation of high Hcy levels should begin early in life.","Aged;Aged, 80 and over;Atrophy;Brain/*pathology;Cerebral Infarction/metabolism/pathology;Cerebrovascular Disorders/*metabolism/*pathology;Cognition/physiology;Female;Homocysteine/*metabolism;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Randomized Controlled Trials as Topic;Stroke/physiopathology/psychology","Sachdev, P.",2004,Nov 15,10.1016/j.jns.2004.09.006,0,
1565,CADASIL presenting as status migrainosus and persisting aura without infarction,Different types of migraine have been reported in 20-40% of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We describe a novel migrainous manifestation of CADASIL consisting in status migrainosus and persistent aura without infarction. The symptoms resolved after i.v. treatment with lorazepam and mannitol. © Springer-Verlag 2008.,ibuprofen;ketorolac;lorazepam;mannitol;Notch3 receptor;sumatriptan;adult;article;CADASIL;case report;confusion;distal paresthesia;electroencephalogram;female;genetic analysis;headache;hemianopia;human;human tissue;migraine with aura;neurologic examination;nuclear magnetic resonance imaging;oral paresthesia;priority journal;psychomotor disorder;single drug dose;skin biopsy;speech disorder;tonic clonic seizure;visual disorder;visual field defect,"Sacco, S.;Rasura, M.;Cao, M.;Bozzao, A.;Carolei, A.",2009,,,0,
1566,A generative model for image segmentation based on label fusion,"We propose a nonparametric, probabilistic model for the automatic segmentation of medical images, given a training set of images and corresponding label maps. The resulting inference algorithms rely on pairwise registrations between the test image and individual training images. The training labels are then transferred to the test image and fused to compute the final segmentation of the test subject. Such label fusion methods have been shown to yield accurate segmentation, since the use of multiple registrations captures greater inter-subject anatomical variability and improves robustness against occasional registration failures. To the best of our knowledge, this manuscript presents the first comprehensive probabilistic framework that rigorously motivates label fusion as a segmentation approach. The proposed framework allows us to compare different label fusion algorithms theoretically and practically. In particular, recent label fusion or multiatlas segmentation algorithms are interpreted as special cases of our framework. We conduct two sets of experiments to validate the proposed methods. In the first set of experiments, we use 39 brain MRI scans-with manually segmented white matter, cerebral cortex, ventricles and subcortical structures-to compare different label fusion algorithms and the widely-used FreeSurfer whole-brain segmentation tool. Our results indicate that the proposed framework yields more accurate segmentation than FreeSurfer and previous label fusion algorithms. In a second experiment, we use brain MRI scans of 282 subjects to demonstrate that the proposed segmentation tool is sufficiently sensitive to robustly detect hippocampal volume changes in a study of aging and Alzheimer's Disease.","Algorithms;Brain/ anatomy & histology;Computer Simulation;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Models, Anatomic;Models, Neurological;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Sabuncu, M. R.;Yeo, B. T.;Van Leemput, K.;Fischl, B.;Golland, P.",2010,Oct,10.1109/tmi.2010.2050897,0,
1567,Neuropsychological impairment correlates with hypoperfusion and hypometabolism but not with severity of white matter lesions on MRI in patients with cerebral microangiopathy,"BACKGROUND AND PURPOSE: Cerebral microangiopathy, indicated on MRI by lacunar infarctions (LI) and deep white matter lesions (DWML), is said to lead to vascular dementia. METHODS: Fifty-seven patients with proven cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose metabolism (rMRGlu) and compared with 19 age-matched controls. The findings were correlated with results of extensive neuropsychological testing, as well as with MRI findings. A special head holder ensured reproducibility of positioning during rCBF (single-photon emission CT [SPECT]), rMRGlu (positron emission tomography [PET]), and MR imaging. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. LI and DWML were graded by number and extent. RESULTS: Even with severe DWML and multiple LI, rCBF and rMRGlu values were not reduced. ANOVAs identified brain atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values in both cortex and white matter. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns such as LI and DWML did not. Factor analysis revealed no correlation of LI and DWML with rCBF, rMRGlu, atrophy, and neuropsychological deficits, showing instead positive correlations between rCBF, rMRGlu, and neuropsychological performance and negative correlations of the latter 3 with brain atrophy. CONCLUSIONS: From these data, we conclude that LI and DWML are epiphenomena that may morphologically characterize cerebral microangiopathy but do not in themselves indicate cognitive impairment. Dementia or neuropsychological deficits, by contrast, are reflected exclusively by functional imaging parameters (rCBF, rMRGlu) and cerebral atrophy.","Adult;Aged;Aged, 80 and over;Cerebrovascular Circulation;Cerebrovascular Disorders/metabolism/ pathology/physiopathology/psychology;Female;Glucose/metabolism;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychology;Severity of Illness Index","Sabri, O.;Ringelstein, E. B.;Hellwig, D.;Schneider, R.;Schreckenberger, M.;Kaiser, H. J.;Mull, M.;Buell, U.",1999,Mar,,0,
1568,"One-year follow-up of neuropsychology, MRI, rCBF and glucose metabolism (rMRGlu) in cerebral microangiopathy","Background: MRI shows lacunar infarctions (LI), deep white matter lesions (DWML) and atrophy in cerebral microongiopathy, which is said to lead to vascular dementia. In a first trial series on 57 patients with confirmed pure cerebral microangiopathy (without concomitant macroangiopathy), neuropsychological impairment and (where present) brain atrophy correlated with decreased rCBF and rMRGlu. LI and DWML did not correlate with either neuropsychological impairment or decreased rCBF/rMRGlu. This study was done one year later to detect changes in any of the study parameters. Methods: 26 patients were re-examined for rCBF, rMRGlu, LI, DWML, atrophy and neuropsychological performance (7 cognitive, 3 mnestic, 4 attentiveness tests). Using a special head holder for exact repositioning, rCBF (SPECT) and rMRGlu (PET) were measured and imaged slice by slice. White matter/cortex were quantified using MRI-defined ROIs. Results: After one year the patients did not show significant decreases in rCBF or rMRGlu either in cortex or in white matter (p >0.05), nor did any patient show LI, DWML or atrophy changes on MRI. There were no significant neuropsychological decreases (p >0.05). Conclusions: Cerebral microangiopathy ought to show progressive neuropsychological, functional (rCBF, rMRGlu) and morphological deterioration over periods >1 year. It is unlikely that direct cortical damage (e.g., incomplete infarction) is responsible for neuropsychological impairment since one-year follow-up of our patients revealed no progression of brain atrophy or any other cortical damage.",,"Sabri, O.;Hellwig, D.;Schreckenberger, M.;Schneider, R.;Kaiser, H. J.;Wagenknecht, G.;Setani, K.;Reinartz, P.;Zimny, M.;Mull, M.;Ringelstein, E. B.;Büll, U.",2000,2000,,0,
1569,"Correlation of neuropsychological, morphological and functional (regional cerebral blood flow and glucose utilization) findings in cerebral microangiopathy","Cerebral microangiopathy, indicated in MRI by lacunar infarctions (LIs) and deep white matter lesions (DWMLs), is said to be accompanied by vascular dementia, which is reportedly caused by LI and DWML. METHODS: To confirm this assumption, 57 patients with cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose utilization (rMRGlu) in both white matter and cortex, and these findings were correlated to the results of extensive neuropsychological testing (cognitive, mnestic and attentiveness tests), as well as to MRI findings. A special head holder ensured reproducibility of positioning during measurement of rCBF (99mTc-HMPAO SPECT) and rMRGlu (18F-FDG PET) and MRI. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. The rMRGlu was calculated according to Sokoloff, and rCBF was determined from normalization to the cerebellum. LI and DWML were graded by number and extent. Brain atrophy was classified as no to slight inner and/or outer atrophy (Group A) or moderate-to-severe inner and outer atrophy (Group B). RESULTS: Even in severe DWMLs and in multiple LIs, rCBFs and rMRGlu values were not reduced. Analysis of variance identified atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values (p < 0.05). However, 60% of patients (19 of 31) with neuropsychological deficits in attentiveness tests and 61% of patients (23 of 38) with mnestic deficits belonged to Group A and revealed decreased rCBF and rMRGlu values. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns, such as LI and DWML, did not. CONCLUSION: We conclude that LI and DWML are epiphenomena that morphologically characterize cerebral microangiopathy. Dementia or neuropsychological deficits, however, are exclusively reflected by functional criteria (rCBF and rMRGlu), as long as cerebral atrophy does not occur.","Aged;Brain/pathology/*physiopathology/radionuclide imaging;Cerebral Infarction/*diagnosis/physiopathology;Cerebrovascular Circulation/*physiology;Cohort Studies;Dementia, Vascular/*diagnosis/physiopathology;Female;Fluorine Radioisotopes;Fluorodeoxyglucose F18;Glucose/*metabolism;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Radiopharmaceuticals;Reproducibility of Results;Technetium Tc 99m Exametazime;Tomography, Emission-Computed;Tomography, Emission-Computed, Single-Photon","Sabri, O.;Hellwig, D.;Schreckenberger, M.;Cremerius, U.;Schneider, R.;Kaiser, H. J.;Doherty, C.;Mull, M.;Ringelstein, E. B.;Buell, U.",1998,Jan,,0,
1570,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Clinical, neuroimaging, pathological and genetic study of a large Italian family","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. The gene has been recently mapped, in two French families, on chromosome 19q12 between two highly polymorphic genetic markers. We report on a new large Italian family affected with this disease, which is characterized by recurrent stroke episodes, focal neurological deficits progressing to pseudo-bulbar palsy, and dementia. Multiple deep infarcts and diffuse leucoencephalopathy were revealed by MRI and brain histopathology showed abnormalities of arterial media. A genetic study performed with microsatellite markers from region 19q12 showed that the disease locus lies in an interval largely overlapping that already described and is closely linked to two microsatellite markers, D19S212 and D19S222. A joint analysis of genotypic and phenotypic data shows that diffuse leucoencephalopathy is a reliable sign of the disease in otherwise normal 50%-risk subjects over the age 30 years and that penetrance of stroke episodes or dementia is most likely complete around age 60 years.","Adult;Brain Diseases/*genetics/pathology;Cerebral Infarction/*genetics/pathology;Cerebrovascular Disorders/*genetics/pathology;Chromosomes, Human, Pair 19;Dementia/genetics/pathology;Female;Genetic Markers;Humans;Italy;Male;Middle Aged;Pedigree","Sabbadini, G.;Francia, A.;Calandriello, L.;Di Biasi, C.;Trasimeni, G.;Gualdi, G. F.;Palladini, G.;Manfredi, M.;Frontali, M.",1995,Feb,,0,
1571,Diffusion tensor imaging of brain white matter in huntington gene mutation individuals,"Objective: To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease. Methods: We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls). We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy. Results: We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups. Conclusion: White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.",adult;article;Beck Depression Inventory;clinical article;cognitive defect;controlled study;corpus callosum;diffusion tensor imaging;disease duration;disease severity;external capsule;female;follow up;fractional anisotropy;gene mutation;human;Huntington chorea;image processing;inferior longitudinal fasciculus;male;middle aged;Mini Mental State Examination;molecular diagnosis;Montreal cognitive assessment;nuclear magnetic resonance imaging;white matter,"Saba, R. A.;Yared, J. H.;Doring, T. M.;Borges, V.;Ferraz, H. B.",2017,,10.1590/0004-282x20170085,0,
1572,"Cognition, structural brain changes and complicated grief. A population-based study","BACKGROUND: Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. METHOD: The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. RESULTS: Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). CONCLUSIONS: Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.",Aged;Brain/ pathology/physiopathology;Cognition Disorders/ pathology/physiopathology;Cross-Sectional Studies;Female;Grief;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Netherlands;Risk Factors,"Saavedra Perez, H. C.;Ikram, M. A.;Direk, N.;Prigerson, H. G.;Freak-Poli, R.;Verhaaren, B. F.;Hofman, A.;Vernooij, M.;Tiemeier, H.",2015,May,10.1017/s0033291714002499,0,
1573,Hippocampal and entorhinal structures in subjective memory impairment: a combined MRI volumetric and DTI study,"BACKGROUND: Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimer's disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. METHODS: A total of 45 participants (mean age: 70.31 +/- 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. RESULTS: Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. CONCLUSIONS: These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.",Mri;diffusion tensor imaging;entorhinal cortex;hippocampus;subjective memory impairment,"Ryu, S. Y.;Lim, E. Y.;Na, S.;Shim, Y. S.;Cho, J. H.;Yoon, B.;Hong, Y. J.;Yang, D. W.",2017,May,,0,
1574,"Radial Artery Graft Bypass with Endovascular Trapping of the Internal Carotid Artery for Recurrent Carotid Cavernous Fistula: Different Surgical Fields, Different Surgical Considerations","Background Venous infarction in the brainstem caused by venous congestion is an extremely rare complication of traumatic carotid cavernous fistulas (CCFs). This condition requires immediate treatment and a multimodal treatment strategy is needed to prevent recurrence. Case Description A 24-year-old man presented with exophthalmos and chemosis after a bicycle accident. Cerebral angiography showed an engorged right superior ophthalmic vein and a right carotid cavernous fistula. Transvenous coil embolization was successfully performed without severe complications. Two months later, a decline in mental status occurred. Follow-up angiography showed recanalization of the CCF. The patient underwent radial artery graft bypass surgery combined with endovascular trapping of the internal carotid artery. Sylvian veins and other cortical veins became intraoperatively arterialized and we observed marked brain edema after high-flow CCF. After surgery, the patient's mental status recovered and angiography showed good patency of the bypass graft and complete obliteration of the recurrent CCF. Conclusions To ensure prevention of recurrent CCF, internal carotid artery trapping combined with high-flow bypass surgery can be a good salvage treatment for urgent cases in which an endovascular approach already failed.",adult;artery anastomosis;article;brain angiography;brain edema;bypass surgery;carotid cavernous fistula;case report;chemosis;coil embolization;computed tomographic angiography;diffusion weighted imaging;digital subtraction angiography;embolization coil;endovascular surgery;exophthalmos;eye contusion;follow up;human;internal carotid artery;male;mental deterioration;microcatheter;neuroimaging;nuclear magnetic resonance imaging;radial artery;young adult;Axium 3D;Axium Helix;MicroNester,"Ryu, J.;Chang, S.;Choi, S. K.;Lee, S. H.;Chung, Y.",2017,,10.1016/j.wneu.2016.06.091,0,
1575,Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort,"The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly.",Aged;Aging/*pathology/physiology;Atrophy;Cognition Disorders/*pathology/physiopathology;Cohort Studies;Corpus Callosum/*pathology/physiopathology;Female;Follow-Up Studies;Humans;Male;Memory Disorders/*pathology/physiopathology;Psychomotor Disorders/*pathology/physiopathology;Walking/physiology,"Ryberg, C.;Rostrup, E.;Paulson, O. B.;Barkhof, F.;Scheltens, P.;van Straaten, E. C.;van der Flier, W. M.;Fazekas, F.;Schmidt, R.;Ferro, J. M.;Baezner, H.;Erkinjuntti, T.;Jokinen, H.;Wahlund, L. O.;Poggesi, A.;Pantoni, L.;Inzitari, D.;Waldemar, G.",2011,Aug 15,10.1016/j.jns.2011.05.002,0,
1576,Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer's disease,"Amyloid imaging studies of presymptomatic familial Alzheimer's disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer's disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer's disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network. © 2013 The Author).",,"Ryan, N. S.;Keihaninejad, S.;Shakespeare, T. J.;Lehmann, M.;Crutch, S. J.;Malone, I. B.;Thornton, J. S.;Mancini, L.;Hyare, H.;Yousry, T.;Ridgway, G. R.;Zhang, H.;Modat, M.;Alexander, D. C.;Rossor, M. N.;Ourselin, S.;Fox, N. C.",2013,May,,0,
1577,Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease,"Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid beta coding domain APP mutations. As CAA may manifest as white matter hyperintensities (WMH) on magnetic resonance imaging, particularly posteriorly, we investigated WMH in 52 symptomatic FAD patients for associations with mutation position. WMH were visually rated in 39 PSEN1 (18 precodon 200); 13 APP mutation carriers and 25 healthy controls. Ten PSEN1 mutation carriers (5 precodon 200) had postmortem examination. Increased WMH were observed in the PSEN1 postcodon 200 group and in the single APP patient with an amyloid beta coding domain (p.Ala692Gly, Flemish) mutation. WMH burden on MRI correlated with severity of CAA and cotton wool plaques in several areas. The precodon 200 group had younger ages at onset, decreased axonal density and/or integrity, and a greater T-lymphocytic response in occipital deep white matter. Mutation site contributes to the phenotypic and pathological heterogeneity witnessed in FAD.",,"Ryan, N. S.;Biessels, G. J.;Kim, L.;Nicholas, J. M.;Barber, P. A.;Walsh, P.;Gami, P.;Morris, H. R.;Bastos-Leite, A. J.;Schott, J. M.;Beck, J.;Mead, S.;Chavez-Gutierrez, L.;de Strooper, B.;Rossor, M. N.;Revesz, T.;Lashley, T.;Fox, N. C.",2015,Dec,10.1016/j.neurobiolaging.2015.08.026,0,
1578,Cerebral microbleeds in familial Alzheimer's disease,,amyloid precursor protein;presenilin 1;presenilin 2;Alzheimer disease;basal ganglion;brain disease;brain function;brain hemorrhage;brain stem;cerebellum;cerebrovascular disease;diffusion weighted imaging;disease course;disease severity;familial disease;gene mutation;human;hypertension;informed consent;intron;letter;longitudinal study;memory disorder;myoclonus;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;occipital cortex;parietal cortex;patient referral;phenotype;priority journal;protein domain;risk factor;subarachnoid space;temporal cortex;thalamus;three dimensional imaging;vascular amyloidosis;white matter,"Ryan, N. S.;Bastos-Leite, A. J.;Rohrer, J. D.;Werring, D. J.;Fox, N. C.;Rossor, M. N.;Schott, J. M.",2012,,,0,
1579,"Brain volumes in late life: gender, hormone treatment, and estrogen receptor variants","Structural imaging studies suggest gender differences in brain volumes; however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippocampal volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippocampal and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.","Aged;Aging/ pathology;Alleles;Atrophy/genetics;Brain/ pathology;Estradiol/administration & dosage;Estrogen Receptor alpha/ genetics;Estrogen Receptor beta/ genetics;Estrogen Replacement Therapy;Female;Humans;Magnetic Resonance Imaging;Male;Polymorphism, Genetic;Progesterone/administration & dosage;Sex Characteristics","Ryan, J.;Artero, S.;Carriere, I.;Scali, J.;Maller, J. J.;Meslin, C.;Ritchie, K.;Scarabin, P. Y.;Ancelin, M. L.",2014,Mar,10.1016/j.neurobiolaging.2013.09.026,0,
1580,Association of MTHFR C677T Genotype with Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype,"Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods-We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results-MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions-MTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes.",,"Rutten-Jacobs, L. C. A.;Traylor, M.;Adib-Samii, P.;Thijs, V.;Sudlow, C.;Rothwell, P. M.;Boncoraglio, G.;Dichgans, M.;Meschia, J.;Maguire, J.;Levi, C.;Rost, N. S.;Rosand, J.;Hassan, A.;Bevan, S.;Markus, H. S.",2016,1,,0,
1581,Common NOTCH3 Variants and Cerebral Small-Vessel Disease,"Background and Purpose-The most common monogenic cause of cerebral small-vessel disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, caused by NOTCH3 gene mutations. It has been hypothesized that more common variants in NOTCH3 may also contribute to the risk of sporadic small-vessel disease. Previously, 4 common variants (rs10404382, rs1043994, rs10423702, and rs1043997) were found to be associated with the presence of white matter hyperintensity in hypertensive community-dwelling elderly. Methods-We investigated the association of common single nucleotide polymorphisms (SNPs) in NOTCH3 in 1350 patients with MRI-confirmed lacunar stroke and 7397 controls, by meta-analysis of genome-wide association study data sets. In addition, we investigated the association of common SNPs in NOTCH3 with MRI white matter hyperintensity volumes in 3670 white patients with ischemic stroke. In each analysis, we considered all SNPs within the NOTCH3 gene, and within 50-kb upstream and downstream of the coding region. A total of 381 SNPs from the 1000 genome population with a mean allele frequency >0.01 were included in the analysis. A significance level of P<0.0015 was used, adjusted for the effective number of independent SNPs in the region using the Galwey method. Results-We found no association of any common variants in NOTCH3 (including rs10404382, rs1043994, rs10423702, and rs1043997) with lacunar stroke or white matter hyperintensity volume. We repeated our analysis stratified for hypertension but again found no association. Conclusions-Our study does not support a role for common NOTCH3 variation in the risk of sporadic small-vessel disease.",Notch3 receptor;protein variant;adult;article;brain ischemia;brain size;cardiovascular risk;cerebrovascular disease;controlled study;female;gene frequency;genetic association;genetic code;genetic risk;genome;human;hypertension;lacunar stroke;major clinical study;male;nuclear magnetic resonance imaging;population genetics;priority journal;single nucleotide polymorphism;stroke patient;white matter,"Rutten-Jacobs, L. C. A.;Traylor, M.;Adib-Samii, P.;Thijs, V.;Sudlow, C.;Rothwell, P. M.;Boncoraglio, G.;Dichgans, M.;Bevan, S.;Meschia, J.;Levi, C.;Rost, N. S.;Rosand, J.;Hassan, A.;Markus, H. S.",2015,,,0,
1582,The NOTCH3 score: a pre-clinical CADASIL biomarker in a novel human genomic NOTCH3 transgenic mouse model with early progressive vascular NOTCH3 accumulation,"INTRODUCTION: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, leading to toxic NOTCH3 protein accumulation in the small- to medium sized arterioles. The accumulation is systemic but most pronounced in the brain vasculature where it leads to clinical symptoms of recurrent stroke and dementia. There is no therapy for CADASIL, and therapeutic development is hampered by a lack of feasible clinical outcome measures and biomarkers, both in mouse models and in CADASIL patients. To facilitate pre-clinical therapeutic interventions for CADASIL, we aimed to develop a novel, translational CADASIL mouse model. RESULTS: We generated transgenic mice in which we overexpressed the full length human NOTCH3 gene from a genomic construct with the archetypal c.544C > T, p.Arg182Cys mutation. The four mutant strains we generated have respective human NOTCH3 RNA expression levels of 100, 150, 200 and 350 % relative to endogenous mouse Notch3 RNA expression. Immunohistochemistry on brain sections shows characteristic vascular human NOTCH3 accumulation in all four mutant strains, with human NOTCH3 RNA expression levels correlating with age at onset and progression of NOTCH3 accumulation. This finding was the basis for developing the 'NOTCH3 score', a quantitative measure for the NOTCH3 accumulation load. This score proved to be a robust and sensitive method to assess the progression of NOTCH3 accumulation, and a feasible biomarker for pre-clinical therapeutic testing. CONCLUSIONS: This novel, translational CADASIL mouse model is a suitable model for pre-clinical testing of therapeutic strategies aimed at delaying or reversing NOTCH3 accumulation, using the NOTCH3 score as a biomarker.","Age Factors;Analysis of Variance;Animals;Brain/metabolism/*pathology;CADASIL/*genetics/metabolism/pathology;DNA Mutational Analysis;Disease Models, Animal;Gene Expression Regulation/*genetics;Humans;Magnetic Resonance Imaging;Mice;Mice, Inbred C57BL;Mice, Transgenic;Microscopy, Electron;Mutation/*genetics;RNA, Messenger/metabolism;Receptors, Notch/*genetics/*metabolism","Rutten, J. W.;Klever, R. R.;Hegeman, I. M.;Poole, D. S.;Dauwerse, H. G.;Broos, L. A.;Breukel, C.;Aartsma-Rus, A. M.;Verbeek, J. S.;van der Weerd, L.;van Duinen, S. G.;van den Maagdenberg, A. M.;Lesnik Oberstein, S. A.",2015,,10.1186/s40478-015-0268-1,0,
1583,Archetypal NOTCH3 mutations frequent in public exome: implications for CADASIL,"Objective: To determine the frequency of distinctive EGFr cysteine altering NOTCH3 mutations in the 60,706 exomes of the exome aggregation consortium (ExAC) database. Methods: ExAC was queried for mutations distinctive for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), namely mutations leading to a cysteine amino acid change in one of the 34 EGFr domains of NOTCH3. The genotype-phenotype correlation predicted by the ExAC data was tested in an independent cohort of Dutch CADASIL patients using quantified MRI lesions. The Dutch CADASIL registry was probed for paucisymptomatic individuals older than 70 years. Results: We identified 206 EGFr cysteine altering NOTCH3 mutations in ExAC, with a total prevalence of 3.4/1000. More than half of the distinct mutations have been previously reported in CADASIL patients. Despite the clear overlap, the mutation distribution in ExAC differs from that in reported CADASIL patients, as mutations in ExAC are predominantly located outside of EGFr domains 1–6. In an independent Dutch CADASIL cohort, we found that patients with a mutation in EGFr domains 7–34 have a significantly lower MRI lesion load than patients with a mutation in EGFr domains 1–6. Interpretation: The frequency of EGFr cysteine altering NOTCH3 mutations is 100-fold higher than expected based on estimates of CADASIL prevalence. This challenges the current CADASIL disease paradigm, and suggests that certain mutations may more frequently cause a much milder phenotype, which may even go clinically unrecognized. Our data suggest that individuals with a mutation located in EGFr domains 1–6 are predisposed to the more severe “classical” CADASIL phenotype, whereas individuals with a mutation outside of EGFr domains 1–6 can remain paucisymptomatic well into their eighth decade.",cysteine;epidermal growth factor receptor;Notch3 receptor;article;CADASIL;comparative study;computer assisted tomography;controlled study;DNA determination;exome;exome aggregation consortium database;gene;gene mutation;gene sequence;genetic database;genetic variability;genotype phenotype correlation;human;major clinical study;missense mutation;mutation rate;NOTCH3 gene;nuclear magnetic resonance imaging;prevalence;priority journal,"Rutten, J. W.;Dauwerse, H. G.;Gravesteijn, G.;van Belzen, M. J.;van der Grond, J.;Polke, J. M.;Bernal-Quiros, M.;Lesnik Oberstein, S. A. J.",2016,,10.1002/acn3.344,0,
1584,Hypomorphic NOTCH3 alleles do not cause CADASIL in humans,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by stereotyped missense mutations in NOTCH3. Whether these mutations lead to the CADASIL phenotype via a neomorphic effect, or rather by a hypomorphic effect, is subject of debate. Here, we report two novel NOTCH3 mutations, both leading to a premature stop codon with predicted loss of NOTCH3 function. The first mutation, c.307C>T, p.Arg103*, was detected in two brothers aged 50 and 55 years, with a brain MRI and skin biopsy incompatible with CADASIL. The other mutation was found in a 40-year-old CADASIL patient compound heterozygous for a pathogenic NOTCH3 mutation (c.2129A>G, p.Tyr710Cys) and an intragenic frameshift deletion. The deletion was inherited from his father, who did not have the skin biopsy abnormalities seen in CADASIL patients. These individuals with rare NOTCH3 mutations indicate that hypomorphic NOTCH3 alleles do not cause CADASIL. In this study, we address the previously unresolved issue of the role of hypomorphic NOTCH3 alleles in CADASIL. Based on extensive investigations of two families, we show that hypomorphic NOTCH3 alleles do not cause CADASIL. © 2013 WILEY PERIODICALS, INC.",genomic DNA;Notch3 receptor;adult;allele;article;bipolar disorder;brain ischemia;CADASIL;case report;frameshift mutation;gene function;gene mutation;genetic counseling;genome analysis;human;human tissue;lacunar stroke;male;migraine with aura;Mini Mental State Examination;missense mutation;multiplex ligation dependent probe amplification;neuroimaging;neurologic examination;nonsense mutation;nuclear magnetic resonance imaging;pathogenicity;polyneuropathy;priority journal;sarcoidosis;sequence analysis;skin biopsy;stop codon;vibration sense,"Rutten, J. W.;Boon, E. M. J.;Liem, M. K.;Dauwerse, J. G.;Pont, M. J.;Vollebregt, E.;Maat-Kievit, A. J.;Ginjaar, H. B.;Lakeman, P.;van Duinen, S. G.;Terwindt, G. M.;Lesnik Oberstein, S. A. J.",2013,,,0,
1585,APOE e4 polymorphism in young adults is associated with improved attention and indexed by distinct neural signatures,"The APOE e4 allele, which confers an increased risk of developing dementia in older adulthood, has been associated with enhanced cognitive performance in younger adults. An objective of the current study was to compare task-related behavioural and neural signatures for e4 carriers (e4+) and non-e4 carriers (e4-) to help elucidate potential mechanisms behind such cognitive differences. On two measures of attention, we recorded clear behavioural advantages in young adult e4+ relative to e4-, suggesting that e4+ performed these tasks with a wider field of attention. Behavioural advantages were associated with increased task-related brain activations detected by fMRI (BOLD). In addition, behavioural measures correlated with structural measures derived from a former DTI analysis of white matter integrity in our cohort. These data provide clear support for an antagonistic pleiotropy hypothesis--that the e4 allele confers some cognitive advantage in early life despite adverse consequences in old age. The data implicate differences in both structural and functional signatures as complementary mediators of the behavioural advantage.","Adolescent;Adult;Apolipoprotein E4/*genetics;Attention/*physiology;Brain/*physiology;*Brain Mapping;Diffusion Magnetic Resonance Imaging;Female;Heterozygote;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Polymorphism, Single Nucleotide/*genetics;Young Adult","Rusted, J. M.;Evans, S. L.;King, S. L.;Dowell, N.;Tabet, N.;Tofts, P. S.",2013,Jan 15,10.1016/j.neuroimage.2012.10.010,0,
1586,Alzheimer disease: measuring loss of cerebral gray matter with MR imaging,"The distributions of the cerebral gray matter, the white matter, and the intracranial cerebrospinal fluid (CSF) were measured in 14 patients with Alzheimer disease (AD) and in 14 healthy control subjects. The measurements, derived from two specifically designed magnetic resonance inversion-recovery sequences, compensate for partial signal averaging. The percentage of the gray matter in the brains of AD patients (44.9% +/- 4.4) was significantly lower than in control subjects (50.2% +/- 3.2). The most significant reduction (P less than .001) occurred in the temporal lobes (13.8%) and a central region (12.8); the reduction in frontal lobe (11.2%) and occipital lobe (9.2%) was also statistically significant (P less than .01). There was an increase in the CSF volume in the temporal, occipital, and frontal regions; no region showed a significant difference in the white matter content. The findings of diffuse changes and temporal lobe involvement in AD are consistent with pathologic observations of cortical cell loss.","Aged;Alzheimer Disease/cerebrospinal fluid/ diagnosis;Brain/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Temporal Lobe/pathology","Rusinek, H.;de Leon, M. J.;George, A. E.;Stylopoulos, L. A.;Chandra, R.;Smith, G.;Rand, T.;Mourino, M.;Kowalski, H.",1991,Jan,10.1148/radiology.178.1.1984287,0,
1587,Retinal nerve fiber layer thinning in CADASIL: an optical coherence tomography and MRI study,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a genetic form of small-vessel disease causing subcortical dementia. A relevant role of axonal injury was recently proposed to explain disability and cognitive decline in this disease. The retinal nerve fiber layer (RNFL) is the only part of the brain where unmyelinated axons can be visualized and quantified in vivo. Their assessment may be an easily reproducible marker of neurodegenerative processes. The aim of this study was to investigate axonal degeneration in CADASIL by measuring RNFL thickness and correlating it with MRI measures of global and regional cerebral atrophy. METHODS: RNFL thickness was measured using optical coherence tomography in 17 CADASIL patients. Average values per quadrant (temporal, superior, nasal, inferior) and overall values were compared with those of normal sex- and age-matched subjects. Data of 13 patients were analyzed for correlations with MRI-based global and regional brain volumes normalized for head size. RESULTS: RNFL thickness was significantly reduced in CADASIL patients with respect to controls (p < 0.05). No significant correlations were found between RNFL thinning and brain atrophy. CONCLUSIONS: RNFL thinning suggests that retinal axonal loss occurs in CADASIL, even in the absence of subjective visual deficit.","Adult;Aged;Atrophy;Axons/*pathology;CADASIL/*diagnosis/pathology/physiopathology;Case-Control Studies;Color Vision;Diagnostic Techniques, Ophthalmological;Eye Movements;Female;Humans;Italy;*Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Retinal Neurons/*pathology;*Tomography, Optical Coherence;Visual Acuity","Rufa, A.;Pretegiani, E.;Frezzotti, P.;De Stefano, N.;Cevenini, G.;Dotti, M. T.;Federico, A.",2011,,10.1159/000321339,0,
1588,Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"BACKGROUND AND PURPOSE - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic microangiopathy with prevalently cerebral manifestations. Among the causes of death, sudden unexpected death seems to occur in a significant number of CADASIL patients. Because potential causes of sudden unexpected death may include cardiac arrhythmias and myocardial infarction, we evaluated risk factors for life-threatening arrhythmias, such as reduced heart rate variability, sympathetic overactivity and QT interval (QTc) prolongation, in 23 CADASIL patients. The relationship of these changes with brain MRI pattern was also investigated. METHODS - Frequency domain measures of heart rate variability (10 minutes recordings) and QTc interval were recorded in 23 CADASIL patients (17 males, 6 females) and 22 healthy age- and sex-matched control subjects. The following heart rate variability spectral parameters were considered at rest during spontaneous and controlled breathing (Cb): total power, very-low-frequency component, low-frequency component, high-frequency component, low-frequency/high-frequency ratio, and Cb-total power, Cb-very-low-frequency component, Cb-low-frequency component, Cb-high-frequency component, Cb-low-frequency/high-frequency ratio. R-to-R wave and QTc interval were also analyzed. All data were statistically compared between CADASIL and control subjects. Conventional brain MRI was performed in patients with CADASIL and T1-weighted and T2-weighted lesion volumes, and were compared with each spectral component of the tachogram. RESULTS - During spontaneous and controlled breathing, total power spectrum and all spectral components (very low frequency component, high-frequency component, low-frequency component) of heart rate variability were significantly reduced in CADASIL patients with respect to controls (P<0.05). The low-frequency/high-frequency component ratio was significantly higher in CADASIL patients than in controls. No significant correlation between heart rate variability spectral parameters and other variables including total brain T2-weighted and T1-weighted lesion volumes were observed in CADASIL subjects. CONCLUSIONS - We found a statistically significant reduction in all frequency domain parameters of heart rate variability associated with a higher low frequency/high frequency ratio for CADASIL patients with respect to normal subjects. These data are consistent with autonomic derangement and suggests that CADASIL patients may be at risk for life-threatening arrhythmias. This could at least in part explain their higher recurrence of sudden unexpected death and should be taken into account in planning therapy. © 2007 American Heart Association, Inc.",adult;aged;article;autonomic nervous system;brain damage;breathing;CADASIL;clinical article;controlled study;correlation analysis;disease association;female;heart arrhythmia;heart rate variability;human;male;nuclear magnetic resonance imaging;priority journal;QT interval;R wave;risk factor;statistical analysis;sympathetic tone,"Rufa, A.;Guideri, F.;Acampa, M.;Cevenini, G.;Bianchi, S.;De Stefano, N.;Stromillo, M. L.;Federico, A.;Dotti, M. T.",2007,,,0,
1589,Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic form of subcortical ischemic vascular dementia (SIVD). The most common vascular risk factors are unremarkable in CADASIL; however, studies on systemic blood pressure (BP) changes over time are substantially lacking. Because BP instability is a relevant risk factor for developing or worsening white matter changes in sporadic SIVD, we aimed to study the BP profile of CADASIL to investigate its relationship with cognitive decline and white matter injury. METHODS: Twenty-four-hour ambulatory BP monitoring was performed in a group of 14 CADASIL patients (12 males and 2 females) and in a group of 15 healthy age-matched control subjects. The following BP variables were compared between the 2 groups: mean daytime and nighttime systolic, diastolic, and mean arterial BP (SABPday, DABPday, and MABPday, and SABPnight, DABPnight, and MABPnight) and nocturnal percentage decline in arterial BP (%MABP reduction). Cognitive performances were tested by mini mental status examination (MMSE), and brain MRI was performed to extrapolate the T2-weighted lesion volume (LV) in each CADASIL patient. The 24-hour arterial BP variables were compared between CADASIL and controls. In addition, for CADASIL patients only, MMSE, LV, and age were compared with each pressure variable. RESULTS: Patients with CADASIL showed a significant reduction (P<0.05) of SABPday, DABPday, MABPday and %MABP decline with respect to controls. In addition, MMSE of CADASIL subjects correlated significantly (P<0.0001) with daytime MABP. CONCLUSIONS: The low systemic BP profile observed in CADASIL patients was specifically attributable to reduced diurnal BP values. This may further affect cerebral hemodynamics and increase the risk of cognitive impairment in these patients. The pathogenesis of abnormal BP profile in CADASIL remains to be clarified. It is likely that central and peripheral mechanisms controlling BP variations are involved.","Adolescent;Blood Pressure;Blood Pressure Monitoring, Ambulatory;CADASIL [epidemiology] [physiopathology];Cerebral Infarction [epidemiology] [genetics] [physiopathology];Circadian Rhythm;Comorbidity;Depression [epidemiology];Hypercholesterolemia [epidemiology];Hyperhomocysteinemia [epidemiology];Magnetic Resonance Imaging;Migraine Disorders [epidemiology];Risk Factors;Adult[checkword];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Rufa, A.;Dotti, M. T.;Franchi, M.;Stromillo, M. L.;Cevenini, G.;Bianchi, S.;Stefano, N.;Federico, A.",2005,,10.1161/01.str.0000190832.17620.25,0,
1590,Acute unilateral visual loss as the first symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Background. Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a cerebrovascular disorder with almost exclusively neurological symptoms, the arteriopathy is generalized and involves choroidal and retinal vasculature as demonstrated by fluorescein angiographic and ocular electrophysiological abnormalities. The occurrence of acute visual loss due to nonarteritic anterior ischemic optic neuropathy (NAION) has not previously been reported in CADASIL. Objective: To describe acute visual loss due to NAION as a possible manifestation of CADASIL. Patients and Methods: The patient was a 60-year-old man with subcortical diffuse leukoencephalopathy, multi-infarct dementia, tetraparesis, visual loss, and a family history of stroke. We performed clinical and neuroophthalmological evaluation, electrophysiological assessment, brain magnetic resonance imaging, and genetic screening for mutations or small deletions of the Notch3 gene, (causing CADASIL). Results: The patient's first symptom was acute visual loss in the right eye due to NAION at age 27 years, in absence of the common cardiovascular risk factors and before any neurological impairment. The patient was reevaluated at age 60 years, and neuro-ophthalmological examination showed optic disc atrophy in the right eye with arteriolar narrowing and a reduction in visual acuity in the left eye. Fluorescein angiography of the right eye showed evidence of persistent peripapillary hypofluorescence with a retinal pigment epithelial windows defect in the inferior temporal area. Pattern reversal visual evoked potentials were abolished in the right eye. The P100 latency of the left eye was delayed and reduced in amplitude. The diagnosis of CADASIL was confirmed by molecular analysis (heterozygotes for the C406T mutation on exon 3 of the Notch3 gene). There was a family history of cerebrovascular disorders and ocular impairment. Conclusions: Visual loss due to transient or stable ischemic events involving the optic nerve head should be considered in the CADASIL phenotype. The possibility of CADASIL should also be evaluated in patients with NAION who do not have cardiovascular risk factors but do have a family history of stroke.",,"Rufa, A.;De Stefano, N.;Dotti, M. T.;Bianchi, S.;Sicurelli, F.;Stromillo, M. L.;D'Aniello, B.;Federico, A.",2004,April,,0,
1591,Acute vestibular syndrome in a patient with cerebral autosomal dominant leukoencephalopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of small vessel disease in which the pons may show lacunar infarcts and leukoaraiosis. Acute pure vestibular syndrome may be due to caudal pontine lesions and is probably underestimated. We describe a case of CADASIL with acute vestibular syndrome mimicking peripheral vestibulopathy, and evidence of focal infarction in the ponto-medullary junction at gadolinium-enhanced MRI including diffusion-weighted imaging, involving the area of the right vestibular nucleus and root entry zone of the ipsilateral vestibular nerve bundle. In CADASIL, both focal brainstem lesions and leukoaraiosis may parallel supratentorial white matter changes and may be related to poor outcome. Their actual extent should be evaluated in longitudinal studies that might predict clinical outcome and progression of disability. © 2008 Elsevier B.V. All rights reserved.",,"Rufa, A.;Cerase, A.;Monti, L.;Battisti, C.;Forte, F.;Federico, A.;Dotti, M. T.",2008,15,,0,
1592,Plasma levels of asymmetric dimethylarginine in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy,"BACKGROUND: Asymmetric dimethylarginine (ADMA) is a marker of endothelial dysfunction and a new independent risk factor for adverse cerebrovascular events in small vessel disease. Conversely, L-arginine (LARG) may have a protective role. METHODS: To assess ADMA, LARG levels and LARG/ADMA ratio in 16 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and normal controls, and to look for possible correlations with white matter changes. Plasma levels of ADMA and LARG were assayed by high-performance liquid chromatography in all subjects. The overall T(1) and T(2) lesion load was obtained from brain MRI of patients with CADASIL. RESULTS: ADMA plasma concentrations (1.5 +/- 2.0 microM) were significantly higher (p < 0.05) in CADASIL patients than in controls (0.35 +/- 0.075 microM). Analyzing only CADASIL subjects, an inverse borderline-significant correlation was found between LARG/ADMA (190 +/- 20) and T(2)-weighted lesion volumes (57.9 +/- 46.5; r = -0.578, p = 0.024). CONCLUSION: Our results may indicate the possible coexistence of endothelial dysfunction in CADASIL patients, broadening the range of potentially pathogenetic mechanisms in this disease and providing insights for future therapeutic strategies.","Adult;Antihypertensive Agents/therapeutic use;Arginine/*analogs & derivatives/blood;Biomarkers;Brain/pathology;CADASIL/*blood/complications/genetics/pathology;Chromatography, High Pressure Liquid;Endothelium, Vascular/pathology;Female;Humans;Hypertension/blood/complications/drug therapy;Lipids/blood;Magnetic Resonance Imaging;Male;Middle Aged;Receptors, Notch/deficiency/genetics/physiology;Risk Factors","Rufa, A.;Blardi, P.;De Lalla, A.;Cevenini, G.;De Stefano, N.;Zicari, E.;Auteri, A.;Federico, A.;Dotti, M. T.",2008,,10.1159/000166840,0,
1593,Conversion of amnestic Mild Cognitive Impairment to Dementia of Alzheimer type is independent to memory deterioration,"Background: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. Aim: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). Methods and Materials: One hundred nineteen subjects consecutively recruited who met the operational criteria for AMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. Results: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 ± 8.5 vs. 69.2 ± 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 ± 3.9 vs 6.7 ± 3.4; p = .000) and by MMSE (mean score 26.1 ± 1.9 vs. 27.3 ± 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 ± 0.4 vs 0.1 ± 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.74 ± 0.8 vs. 0.1 ± 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p=0.000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. Conclusions: In subjects with AMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up. Copyright © 2007 John Wiley & Sons, Ltd.",age distribution;aged;Alzheimer disease;amnesia;article;brain damage;cognitive defect;computer assisted tomography;controlled study;daily life activity;disease classification;disease severity;female;functional assessment;human;image analysis;logistic regression analysis;major clinical study;male;memory disorder;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;psychologic test;risk factor;scoring system;verbal memory;white matter,"Rozzini, L.;Chilovi, B. V.;Conti, M.;Bertoletti, E.;Delrio, I.;Trabucchi, M.;Padovani, A.",2007,,,0,
1594,Estrogen and cognition in women: Potential vascular mechanisms,"Background: Traditional cardiovascular risk factors increase the risk of Alzheimer's disease (AD). The loss of estrogen (E<sub>2</sub>) with menopause appears to augment the age-associated increase in these risk factors, which may help explain the additional increased risk of AD in aging women. E<sub>2</sub> helps maintain neuronal integrity, particularly in the prefrontal cortex (PFC) which supports executive function and working memory, and is vulnerable in AD. E<sub>2</sub> is also vasoprotective. E<sub>2</sub>-deficient postmenopausal women show arterial stiffening and impaired endothelial function compared to age-matched premenopausal women; these impairments are attenuated with E<sub>2</sub>-based hormonal therapy. Arterial stiffening and endothelial dysfunction have been linked to small-vessel cerebrovascular disease and cognitive impairment. Mechanisms for the effects of E<sub>2</sub> on cognition are not known, but acute changes in both vascular function and brain activation occur with surgical or pharmacologic ovarian suppression. This study is investigating whether vascular dysfunction mediates the negative effects of E<sub>2</sub> on brain activation. Methods: 34 healthy, premenopausal women (40-60y) randomized to 6-months of gonadotropin releasing hormone agonist (Gn- RHag) or placebo as part of an ongoing study will be enrolled. Measures of 1) vascular function ([carotid artery compliance-ultrasound] and endothelial function [brachial artery flow-mediated dilation]); and 2) PFC activation (fMRI during a working memory task) are obtained at baseline and 6-months. To isolate the effects of E<sub>2</sub>, participants randomized to GnRHag (n=17) receive 3 additional months of GnRHag with E<sub>2</sub> add-back, with outcomes assessed at 9-months. Expected Results: GnRHag treatment will decrease arterial compliance and endothelial function, and these changes will be correlated with decreased PFC activation. Changes observed with Gn- RHag will be reversed with E<sub>2</sub> add-back. Conclusion: This study is a novel investigation of vascular dysfunction as a possible mechanism underlying the negative effects of E<sub>2</sub>-deficiency on cognition. Use of a controlled experimental model of ovarian suppression and incorporation of an E<sub>2</sub> add-back condition will examine the effects of E<sub>2</sub>, independent of age or other ovarian hormones. Results will inform future studies investigating new sex-specific therapeutic or lifestyle interventions to prevent cognitive decline in aging women.",cognition;female;human;American;geriatrics;society;brain;premenopause;risk;artery compliance;arterial stiffness;working memory;aging;menopause;hormonal therapy;cardiovascular risk;functional magnetic resonance imaging;experimental model;endothelial dysfunction;risk factor;artery blood flow;brachial artery;cerebrovascular disease;ultrasound;postmenopause;carotid artery;executive function;cognitive defect;prefrontal cortex;lifestyle;Alzheimer disease;estrogen;placebo;gonadorelin agonist;hormone,"Royer, E.;Moreau, K.;Kohrt, W.;Hildreth, K.",2015,,10.1111/jgs.13439,0,
1595,"""Silent stroke"": An oxymoron meaning ""dementia""","Brain MRI demonstrates the presence, in a large percent of elderly patients, of ischemic cerebrovascular disease (ICVD), usually as white-matter lesions and lacunar strokes. These lesions are considered clinically silent because they fail to produce sensory or motor deficits. Nonetheless, these lesions disrupt prefrontal-subcortical circuits that mediate executive control functions (ECF). The loss of ECF is manifested as behavioral and mood changes and as executive dysfunction leading to loss of autonomy in activities of daily living and may escape detection. Many cases are likely to be diagnosed as ""Alzheimer disease"" (AD) instead. This is because preclinical levels of AD pathology (ie, sufficient to affect hippocampal and memory function) are very common in the elderly. Mild-cognitive impairment (MCI) has been estimated to affect 40% of persons over the age of 65, in contrast to ""dementia,"" which affects at most 15%. However, memory impairment alone is insufficient for the diagnosis of dementia. Other cognitive domains must also be affected, and these must be sufficient to explain disability. It is very likely that comorbid ""silent"" frontal system ICVD converts a significant fraction of MCI cases to ""AD."" This explains, first, the high prevalence of frontal system ICVD in clinically diagnosed AD; second, the inverse association between ICVD and Braak stage in clinically diagnosed AD; and third, the recent identification of traditional risks factors for ICVD as being also risk factors for AD. © 2004 Elsevier Inc. All rights reserved.",Alzheimer disease;article;behavior disorder;brain function;brain ischemia;cerebrovascular disease;cognitive defect;comorbidity;daily life activity;dementia;diagnostic value;disease association;elderly care;human;independence;memory consolidation;mood disorder;motor dysfunction;nuclear magnetic resonance imaging;prevalence;priority journal;risk factor;sensory dysfunction;cerebrovascular accident;white matter,"Royall, D. R.",2004,,,0,
1596,Example Based Lesion Segmentation,"Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.",Mri;Ms;lesion segmentation;magnetic resonance imaging;patches,"Roy, S.;He, Q.;Carass, A.;Jog, A.;Cuzzocreo, J. L.;Reich, D. S.;Prince, J.;Pham, D.",2014,Feb 15,,0,
1597,White matter abnormalities and structural hippocampal disconnections in amnestic mild cognitive impairment and Alzheimer's disease,"The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer's disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer's disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer's disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer's group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer's disease.",Aged;Alzheimer Disease/complications/pathology/*physiopathology;Amnesia/complications/pathology/*physiopathology;Anisotropy;Cohort Studies;Demography;Diffusion Tensor Imaging;Female;Hippocampus/*pathology/*physiopathology;Humans;Leukoencephalopathies/complications/*pathology/physiopathology;Male;Memory;Mild Cognitive Impairment/complications/pathology/*physiopathology;Nerve Net/pathology/*physiopathology,"Rowley, J.;Fonov, V.;Wu, O.;Eskildsen, S. F.;Schoemaker, D.;Wu, L.;Mohades, S.;Shin, M.;Sziklas, V.;Cheewakriengkrai, L.;Shmuel, A.;Dagher, A.;Gauthier, S.;Rosa-Neto, P.",2013,,10.1371/journal.pone.0074776,0,
1598,Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for beta-amyloid imaging in aging and dementia,"(11)C-Pittsburgh compound-B ((11)C-PiB) is the benchmark radiotracer for imaging of beta-amyloid (Abeta) plaque in Alzheimer disease (AD). (18)F-labeled Abeta tracers subsequently developed for clinical use show higher nonspecific white matter binding and, in some cases, lower cortical binding in AD that could lead to less accurate interpretation of scans. We compared the cortical and white matter binding of a new (18)F-labeled Abeta tracer, (18)F-AZD4694 (recently renamed NAV4694), with (11)C-PiB in the same subjects. METHODS: Forty-five participants underwent PET imaging with (11)C-PiB and (18)F-AZD4694 (25 healthy elderly controls [HCs], 10 subjects with mild cognitive impairment, 7 subjects with probable AD, and 3 subjects with probable frontotemporal dementia). Images were coregistered so that region-of-interest placement was identical on both scans, and standardized uptake value ratios (SUVRs) using the cerebellar cortex as a reference region were calculated between 40 and 70 min after injection for both tracers. RESULTS: (18)F-AZD4694 showed reversible binding kinetics similar to (11)C-PiB, reaching an apparent steady state at 50 min after injection. Both radiotracers showed a similar dynamic range of neocortical SUVR (1.1-3.3 and 1.0-3.2 SUVR for (11)C-PiB and (18)F-AZD4694, respectively) and identical low nonspecific white matter binding, with frontal cortex-to-white matter ratios of 0.7 +/- 0.2 and 1.3 +/- 0.2 for both radiotracers in HCs and AD subjects, respectively. There was an excellent linear correlation between (11)C-PiB and (18)F-AZD4694 neocortical SUVR (slope of 0.95, r = 0.99, P < 0.0001). CONCLUSION: (18)F-AZD4694 displays imaging characteristics nearly identical to those of (11)C-PiB. The low white matter and high cortical binding in AD indicate that this tracer is well suited to both clinical and research use.","Aged;Aging/ metabolism;Amyloid beta-Peptides/ metabolism;Benzofurans/metabolism;Benzothiazoles/metabolism;Brain/metabolism/radionuclide imaging;Dementia/ metabolism/radionuclide imaging;Female;Humans;Hydrocarbons, Fluorinated/metabolism;Male;Molecular Imaging/ methods;Positron-Emission Tomography","Rowe, C. C.;Pejoska, S.;Mulligan, R. S.;Jones, G.;Chan, J. G.;Svensson, S.;Cselenyi, Z.;Masters, C. L.;Villemagne, V. L.",2013,Jun,10.2967/jnumed.112.114785,0,
1599,"Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism","BACKGROUND: Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS: 15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD. FINDINGS: (18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD. INTERPRETATION: (18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/metabolism/ radionuclide imaging;Amyloid beta-Peptides/ metabolism;Aniline Compounds/chemical synthesis;Brain/ radionuclide imaging;Dementia/diagnosis/radionuclide imaging;Diagnosis, Differential;Female;Humans;Image Interpretation, Computer-Assisted;Isotope Labeling;Male;Middle Aged;Plaque, Amyloid/metabolism/radionuclide imaging;Positron-Emission Tomography;Radiopharmaceuticals/chemical synthesis;Stilbenes/chemical synthesis","Rowe, C. C.;Ackerman, U.;Browne, W.;Mulligan, R.;Pike, K. L.;O'Keefe, G.;Tochon-Danguy, H.;Chan, G.;Berlangieri, S. U.;Jones, G.;Dickinson-Rowe, K. L.;Kung, H. P.;Zhang, W.;Kung, M. P.;Skovronsky, D.;Dyrks, T.;Holl, G.;Krause, S.;Friebe, M.;Lehman, L.;Lindemann, S.;Dinkelborg, L. M.;Masters, C. L.;Villemagne, V. L.",2008,Feb,10.1016/s1474-4422(08)70001-2,0,
1600,The effect of midlife physical activity on structural brain changes in the elderly,"Physical activity has been associated with decreased dementia risk in recent studies, but the effects for structural brain changes (i.e. white matter lesions (WML) and/or brain atrophy) have remained unclear. The CAIDE participants were a random population-based sample studied in midlife and re-examined on average 21 years later (n=2000). A subpopulation (n=75; 31 control, 23 MCI, 21 dementia) was MRI scanned at the re-examination. T1-weighted images were used to investigate grey matter (GM) density, and FLAIR-images for WML rating. Persons who actively participated in physical activity at midlife tended to have larger total brain volume (beta 0.12; 95% CI 0.17-1.16, p=0.10) in late-life than sedentary persons even after adjustments. GM volume was larger among the active (beta 0.19; 95% CI 0.07-1.48, p=0.03), whereas the association between midlife physical activity and larger WM volume became non-significant (beta 0.03; 95% CI -0.64 to 0.86, p=0.77) after full adjustments. The differences in the GM density localized mainly in frontal lobes. There was no significant association between midlife physical activity and severe WML later in life after full adjustments (OR 4.20, 95% CI 0.26-69.13, p=0.32).",Aged;Aging/ physiology;Analysis of Variance;Brain/ anatomy & histology/pathology/physiology;Case-Control Studies;Cognition Disorders/ pathology;Cohort Studies;Dementia/ pathology;Female;Humans;Longitudinal Studies;Male;Matched-Pair Analysis;Middle Aged;Motor Activity/ physiology;Organ Size;Population Surveillance;Reference Values,"Rovio, S.;Spulber, G.;Nieminen, L. J.;Niskanen, E.;Winblad, B.;Tuomilehto, J.;Nissinen, A.;Soininen, H.;Kivipelto, M.",2010,Nov,10.1016/j.neurobiolaging.2008.10.007,0,
1601,Binswanger's disease: A cause of dementia in the elderly,"Evaluation of dementia has expanded as our attention to the aged and their maladies has increased. Alzheimer's disease continues to occupy the number one position as a cause of dementia, but vascular dementia also assumes great importance as one of the preventable causes of mental deterioration. Binswanger's disease, a type of vascular or multi-infarct dementia, will be seen more as our diagnostic technologies improve. An appropriate clinical picture combined with normal laboratory values and a CT brain scan with white matter lucencies and frequent basal ganglia infarcts confirm the diagnosis of Binswanger's. Treatment is symptomatic, with prevention of further infarcts.",adult;aged;autopsy;Binswanger encephalopathy;case report;dementia;human;male;priority journal,"Rousseau, P.",1988,,,0,
1602,Cerebral amyloid angiopathy. Two anatomoclinical cases,"Two cases that illustrate the clinical and pathologic features of cerebral amyloid angiopathy are reported. In patients free of systemic amyloidosis, the parietal infiltration of the small cortical and meningeal vessels may remain silent or give rise, in elderly, usually non-hypertensive patients, to two types of neurologic manifestations, e.g. gradual dementia that often runs a subacute course and is accompanied with transient focal deficits, and intracerebral hemorrhages that are often located to a lobe and multiple and may recur; a head injury or a surgical procedure are occasional precipitating factors. The diagnosis may be suggested, as in both of our cases and some of those reported in the literature, by the presence of extensive demyelinization of the hemispheric white matter visualized by computed tomography.",aged;autopsy;brain amyloidosis;case report;central nervous system;computer analysis;computer assisted tomography;dementia;demyelination;diagnosis;histology;human;nervous system;peripheral vascular system,"Roullet, E.;Baudrimont, M.;Singer, B.",1985,,,0,
1603,HIV leucoencephalopathy and TNFα expression in neurones,"Background: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor α (TNFα), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. Objective: To examine the clinical/neuroradiological features of HIVL and the expression of TNFα in HIVL. Methods: Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry. Results: Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNFα was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNFα expression in neurones of the frontal cortex and basal ganglia. Conclusion: This study provides the first demonstration of staining for TNFα in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNFα.",,"Rostasy, K.;Monti, L.;Lipton, S. A.;Hedreen, J. C.;Gonzalez, R. G.;Navia, B. A.",2005,July,,0,
1604,Higher step length variability indicates lower gray matter integrity of selected regions in older adults,"Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower gray matter integrity measured by mean diffusivity (standardized beta. = 0.16; p= 0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both β= 0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease. © 2014 Elsevier B.V.",,"Rosso, A. L.;Olson Hunt, M. J.;Yang, M.;Brach, J. S.;Harris, T. B.;Newman, A. B.;Satterfield, S.;Studenski, S. A.;Yaffe, K.;Aizenstein, H. J.;Rosano, C.",2014,May,,0,
1605,Pathological validation of a CT-based scale for subcortical vascular disease. The OPTIMA Study,"The validity of a computed tomography (CT)-based rating scale that separately rates leukoaraiosis, patchy lesions, and lacunes was tested using neuropathological findings collected on 87 subjects enrolled in the Oxford Project to Investigate Memory and Ageing. The CT-based score (range 0-64) was associated with both small vessel disease (p = 0.015) and microinfarcts (p = 0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on pathology was computed, 0 indicating absent/mild small vessel CVD and no microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher both conditions or severe small vessel CVD. Subjects with a sum score of 0 were decreasing with increasing severity of CT-based score (64, 46, and 25% in those with CT-based scores of 0, 1-38, and 39 and higher), while those with a sum score of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized assessment of subcortical CVD on CT films can be compounded into a unique score that is in good agreement with neuropathology. This supports the validity of the CT-based visual rating scale as a valid tool to detect subcortical vascular changes in elderly persons.","Aged;Aged, 80 and over;Brain/blood supply/pathology/radiography;Cerebral Angiography;Cerebral Arteries/pathology;Dementia, Multi-Infarct/classification/pathology/radiography;Dementia, Vascular/classification/pathology/*radiography;Female;Humans;Leukoaraiosis/classification/pathology/radiography;Longitudinal Studies;Male;Microcirculation/pathology/radiography;Middle Aged;Prospective Studies;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic;Tomography, X-Ray Computed/*statistics & numerical data","Rossi, R.;Joachim, C.;Geroldi, C.;Esiri, M. M.;Smith, A. D.;Frisoni, G. B.",2005,,10.1159/000082350,0,
1606,Nimodipine in subcortical vascular dementia trial,"Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.",calcium channel blocking agent;nimodipine;aged;article;brain cortex;clinical trial;controlled clinical trial;controlled study;double blind procedure;human;international cooperation;methodology;middle aged;multicenter study;multiinfarct dementia;randomized controlled trial;vascularization,"Rossi, R.;Inzitari, D.;Pantoni, L.;del Ser, T.;Erkinjuntti, T.;Wallin, A.;Bianchi, C.;Badenas, J. M.;Beneke, M.",1999,,,0,
1607,Clinical and neuropsychological features associated with structural imaging patterns in patients with mild cognitive impairment,"AIM: To describe the clinical and neuropsychological features of mild cognitive impairment (MCI) patients with medial temporal atrophy (MTA), white matter hyperintensities (WMH), both, and neither and to assess whether the rate of progression differs among groups. METHODS: Ninety-five MCI patients were divided into 4 groups based on the presence of MTA and WMH: 29 were MTA- WMH-, 11 MTA- WMH+, 23 MTA+ WMH-, and 32 MTA+ WMH+. MCI patients were compared with 30 normal subjects. MTA and WMH were assessed with MR-based visual rating scales. Subjects underwent an extensive clinical and neuropsychological investigation. Fifty-six underwent follow-up evaluation. RESULTS: MTA- WMH- had relatively good neuropsychological performance, little vascular and physical comorbidity. MTA- WMH+ performed poorly only on executive neuropsychological tests. MTA+ WMH- patients had poor neuropsychological performances (mainly on memory tests), high physical and vascular comorbidity. MTA+ WMH+ were impaired in neuropsychological performances, had a high number of physical diseases and severe vascular comorbidity. On follow-up, 25% of MTA+ WMH- and 32% of MTA+ WMH+ and none in MTA- WMH- and in MTA- WMH+ converted to dementia (p = 0.05, log rank test). CONCLUSION: Structural neuroimaging can identify subgroups of MCI patients with specific clinical and neuropsychological features.",Aged;Analysis of Variance;Atrophy;Brain Mapping;Cognition Disorders/classification/ pathology/physiopathology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Neuropsychological Tests;Reference Values;Severity of Illness Index;Temporal Lobe/ pathology/physiology/physiopathology,"Rossi, R.;Geroldi, C.;Bresciani, L.;Testa, C.;Binetti, G.;Zanetti, O.;Frisoni, G. B.",2007,,10.1159/000098543,0,
1608,Topographic correspondence between white matter hyperintensities and brain atrophy,"White matter hyperintensities (WMHs) are a common finding in normal elderly persons. We studied the biological damage associated with WMHs by assessing the correspondence between WMH location and regional gray matter loss.Voxel-based morphometry of the gray matter was carried out with statistical parametric mapping on high resolution MR images.Neurologically intact persons with mainly anterior (frontal>parieto-occipital; N = 39) and mainly posterior WMHs (parieto- occipital>frontal; N = 14) were compared with a group devoid of WMHs (N = 80). Subjects with mainly frontal WMHs had bilateral frontal (medial, superior, and inferior gyri) atrophy in gray matter, while subjects with mainly posterior WMHs had more diffuse atrophy, involving mainly the frontal but also the right insular region. Our findings suggest that frontal WMHs are associated with frontal gray matter damage while parietooccipital WMHs seem to have a weaker and more diffuse impact on gray matter.","Adult;Aged;Aging/ pathology;Atrophy/etiology/ pathology/physiopathology;Brain/ pathology/physiopathology;Brain Mapping;Cerebral Cortex/pathology/physiopathology;Cognition Disorders/pathology/physiopathology/psychology;Dementia/ pathology/physiopathology/psychology;Female;Frontal Lobe/pathology/physiopathology;Functional Laterality;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neural Pathways/pathology/physiopathology;Neuropsychological Tests;Predictive Value of Tests","Rossi, R.;Boccardi, M.;Sabattoli, F.;Galluzzi, S.;Alaimo, G.;Testa, C.;Frisoni, G. B.",2006,Jul,10.1007/s00415-006-0133-z,0,
1609,A family with Alzheimer disease and strokes associated with A713T mutation of the APP gene,"Three members of an Italian family with autosomal dominant dementia and multiple strokes had the A713T mutation of the APP gene. The neuropathologic examination of the proband disclosed Alzheimer disease (AD) with severe cerebral amyloid angiopathy and multiple infarcts. This indicates that the A713T mutation of the APP gene, lying at the gamma-secretase cleavage site, can be responsible for AD with symptomatic cerebral amyloid angiopathy.","Alzheimer Disease/*genetics/pathology;Amino Acid Substitution;Amyloid Precursor Protein Secretases;Amyloid beta-Protein Precursor/chemistry/*genetics;Aspartic Acid Endopeptidases;Brain/pathology;Cerebral Amyloid Angiopathy/*genetics/pathology;Cerebral Infarction/*genetics/pathology;Codon/genetics;DNA Mutational Analysis;Disease Progression;Endopeptidases/metabolism;Female;Genes, Dominant;Humans;Italy;Magnetic Resonance Imaging;Male;Middle Aged;*Mutation, Missense;Pedigree;*Point Mutation","Rossi, G.;Giaccone, G.;Maletta, R.;Morbin, M.;Capobianco, R.;Mangieri, M.;Giovagnoli, A. R.;Bizzi, A.;Tomaino, C.;Perri, M.;Di Natale, M.;Tagliavini, F.;Bugiani, O.;Bruni, A. C.",2004,Sep 14,,0,
1610,Grey matter volume alterations in CADASIL: a voxel-based morphometry study,"CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized.",Cadasil;Dartel;Dementia;Vbm,"Rossi Espagnet, M. C.;Romano, A.;Carducci, F.;Calabria, L. F.;Fiorillo, M.;Orzi, F.;Bozzao, A.",2012,Apr,10.1007/s10194-012-0418-9,0,
1611,Relationship of leukoaraiosis to cognitive decline and cognitive aging,"OBJECTIVE: Leukoaraiosis (LA) is a common finding on MRI scans of the elderly. However, its exact relationship to cognitive decline and dementia is in dispute. Because LA involves the paracallosal white matter, we sought to determine if LA, uncomplicated by ischemic lesions or complaints of cognitive impairment, is associated with cognitive loss or difficulties with interhemispheric integration of behavioral functions. METHODS: Two hundred fifty-seven MRI scans with deep white matter changes were screened. After a chart review, 38 patients had uncomplicated LA, and 31 gave informed consent to undergo cognitive and behavioral testing. RESULTS: LA severity was not related to any of the cognitive or behavioral assessments. However, some dependent measures showed medium effect sizes that were in keeping with published findings, indicating that LA has a marginal impact on cognition. In comparison, robust relationships with age were found for certain tasks, suggesting that our cohort size was sufficient to detect meaningful clinical relationships. CONCLUSION: Based on statistical interpretations using effect sizes, LA severity may be better viewed as a biomarker for physiological brain aging that is in advance of chronological age, leaving the elderly individual at greater risk for developing dementia.","Aged;Aged, 80 and over;Aging/*physiology;Cognition Disorders/*physiopathology;Dementia/*physiopathology;Female;Humans;Leukoaraiosis/*pathology;Magnetic Resonance Imaging;Male;Middle Aged;Severity of Illness Index","Ross, E. D.;Hansel, S. L.;Orbelo, D. M.;Monnot, M.",2005,Jun,,0,
1612,1H MRS in stroke patients with and without cognitive impairment,"The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.","0 (Biomarkers);0 (Nerve Tissue Proteins);0 (Neurotransmitter Agents);0 (Protons);30KYC7MIAI (Aspartic Acid);997-55-7 (N-acetylaspartate);N91BDP6H0X (Choline);Aged;Aged, 80 and over;Aspartic Acid/ analogs & derivatives/ metabolism;Biomarkers/metabolism;Cerebral Cortex/ metabolism;Choline/ metabolism;Cognition Disorders/epidemiology/metabolism;Cohort Studies;Comorbidity;Dementia, Vascular/ epidemiology/ metabolism;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Tissue Proteins/metabolism;Neurotransmitter Agents/metabolism;Protons;Risk Assessment/methods;Risk Factors;Severity of Illness Index;Stroke/ epidemiology/ metabolism;Tissue Distribution","Ross, A. J.;Sachdev, P. S.;Wen, W.;Valenzuela, M. J.;Brodaty, H.",2005,Jun,,0,1613
1613,1H MRS in stroke patients with and without cognitive impairment,"The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.","Aspartic Acid [analogs & derivatives] [metabolism];Biomarkers [metabolism];Cerebral Cortex [metabolism];Choline [metabolism];Cognition Disorders [epidemiology] [metabolism];Cohort Studies;Comorbidity;Dementia, Vascular [epidemiology] [metabolism];Magnetic Resonance Imaging;Nerve Tissue Proteins [metabolism];Neurotransmitter Agents [metabolism];Protons;Risk Assessment [methods];Risk Factors;Severity of Illness Index;Stroke [epidemiology] [metabolism];Tissue Distribution;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Ross, A. J.;Sachdev, P. S.;Wen, W.;Valenzuela, M. J.;Brodaty, H.",2005,,10.1016/j.neurobiolaging.2004.07.008,0,
1614,Neurofilament protein levels in CSF are increased in dementia,"The neurofilament is the major cytoskeletal structure of myelinated axons. In this study, CSF levels of the light subunit of the neurofilament protein (NFL) were increased in patients with vascular dementia (VAD), AD, and frontotemporal dementia (FTD) compared with neurologically healthy individuals. Because NFL is localized mainly in myelinated axons, these results suggest that the degeneration of white matter in these disorders causes the increased CSF NFL levels.",neurofilament protein;adult;aged;article;case report;clinical trial;controlled clinical trial;controlled study;cytoskeleton;electrocardiogram;electroencephalogram;enzyme linked immunosorbent assay;female;frontotemporal dementia;human;male;multiinfarct dementia;myelination;nerve degeneration;neurofibrillary tangle;neurofilament;nuclear magnetic resonance imaging;priority journal;protein analysis;white matter,"Rosengren, L. E.;Karlsson, J. E.;Sjögren, M.;Blennow, K.;Wallin, A.",1999,,,0,
1615,Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: approach to targeted treatment trials,"OBJECTIVES: Vascular cognitive impairment (VCI) is a heterogeneous group of cerebrovascular diseases secondary to large and small vessel disease. We hypothesised that biomarkers obtained early in the disease could identify a homogeneous subpopulation with small vessel disease. METHODS: We obtained disease markers in 62 patients with VCI that included neurological findings, neuropsychological tests, multimodal MR and cerebrospinal fluid measurements of albumin ratio, matrix metalloproteinases (MMPs), amyloid-beta1-42 and phosphorylated-tau181. Proton MR spectroscopic imaging showed ischaemic white matter and permeability of the blood-brain barrier (BBB) was measured with dynamic contrast-enhanced MRI. We constructed a 10-point Binswanger disease score (BDS) with subjective and objective disease markers. In addition, an objective set of biomarkers was used for an exploratory factor analysis (EFA) to select patients with BD. Patients were followed for an average of 2 years to obtain clinical consensus diagnoses. RESULTS: An initial BDS of 6 or greater was significantly correlated with a final diagnosis of BD (p<0.05; area under the curve (AUC)=0.79). EFA reduced nine objective biomarkers to four factors. The most predictive of BD was the factor containing the inflammatory biomarkers of increased BBB permeability, elevated albumin index and reduced MMP-2 index (factor 2; AUC=0.78). Both measures independently predicted a diagnosis of BD, and combining them improved the diagnostic accuracy. CONCLUSIONS: Biomarkers predicted the diagnosis of the BD type of subcortical ischaemic vascular disease. Using pathophysiological biomarkers to select homogeneous groups of patients needs to be tested in targeted treatment trials.","Aged;Aged, 80 and over;Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers/analysis/cerebrospinal fluid;Brain Ischemia/cerebrospinal fluid/ diagnosis;Cerebral Small Vessel Diseases/cerebrospinal fluid/ diagnosis;Dementia, Vascular/cerebrospinal fluid/ diagnosis/therapy;Factor Analysis, Statistical;Female;Humans;Magnetic Resonance Imaging;Male;Matrix Metalloproteinase 9/cerebrospinal fluid;Middle Aged;Neuropsychological Tests;Peptide Fragments/cerebrospinal fluid;Predictive Value of Tests;tau Proteins/cerebrospinal fluid","Rosenberg, G. A.;Prestopnik, J.;Adair, J. C.;Huisa, B. N.;Knoefel, J.;Caprihan, A.;Gasparovic, C.;Thompson, J.;Erhardt, E. B.;Schrader, R.",2015,Dec,10.1136/jnnp-2014-309421,0,
1616,Subcortical arteriosclerotic encephalopathy (Binswanger): Computerized tomography,"The subcortical arteriosclerotic encephalopathy of Binswanger is characterized clinically by hypertension, dementia, spasticity, syncope, and seizures. It is usually diagnosed pathologically by the finding in white matter of diffuse demyelination or foci of necrosis plus arteriosclerotic and hypertensive vasculopathy. The authors present a case in which the diagnosis was made on the basis of the clinical course and a computerized tomogram which demonstrated extensive white matter degeneration. Postmortem examination confirmed both the diagnosis and the extent of the degeneration as shown by CT scan.",adult;autopsy;Binswanger encephalopathy;brain atherosclerosis;cardiovascular system;case report;central nervous system;computer assisted tomography;dementia;diagnosis;etiology;histology;histopathology;hypertension;peripheral vascular system;seizure;faintness,"Rosenberg, G. A.;Kornfeld, M.;Stovring, J.;Bicknell, J. M.",1979,,,0,
1617,Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment,"BACKGROUND: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. OBJECTIVES: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. METHODS: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. RESULTS: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. CONCLUSIONS: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;Amnesia/ pathology/psychology;Anisotropy;Brain/ pathology;Cognition Disorders/ pathology/psychology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Mental Status Schedule","Rose, S. E.;McMahon, K. L.;Janke, A. L.;O'Dowd, B.;de Zubicaray, G.;Strudwick, M. W.;Chalk, J. B.",2006,Oct,10.1136/jnnp.2005.074336,0,
1618,Gray and white matter changes in Alzheimer's disease: a diffusion tensor imaging study,"PURPOSE: To investigate microstructural changes in cortical and white matter pathways in patients with Alzheimer's disease using diffusion tensor imaging (DTI). MATERIALS AND METHODS: Measures of mean diffusivity (MD) and fractional anisotropy (FA) were compared in the brains of 13 Alzheimer's disease (AD) patients and a group of 13 aged-matched control participants employing an optimized DTI technique involving a fully automated, voxel-based morphometric (VBM) analysis. RESULTS: After rigorous control for anatomical variation and confounding partial volume effects, we found significantly elevated MD measures within the hippocampus, amygdala, and medial temporal, parietal, and frontal lobe gray matter regions in the AD participants. The largest number of pixels with increased MD was localized bilaterally, within the posterior cingulate gyrus. The FA was significantly reduced within the thalamus, parietal white matter, and posterior limbs of the internal capsule, indicating significant involvement of corticothalamic and thalamocortical radiations. CONCLUSION: This study demonstrates that rigorous VBM analysis of DTI data can be used to investigate microstructural changes in cortical, subcortical, and white matter regions in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Case-Control Studies;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted;Male;Neuropsychological Tests","Rose, S. E.;Janke, A. L.;Chalk, J. B.",2008,Jan,10.1002/jmri.21231,0,
1619,Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging,"A novel MRI method--diffusion tensor imaging--was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Analysis of Variance;Brain/ pathology;Evaluation Studies as Topic;Humans;Magnetic Resonance Imaging/ methods;Middle Aged","Rose, S. E.;Chen, F.;Chalk, J. B.;Zelaya, F. O.;Strugnell, W. E.;Benson, M.;Semple, J.;Doddrell, D. M.",2000,Oct,,0,
1620,Diffusion tensor imaging in presymptomatic and early Huntington's disease: Selective white matter pathology and its relationship to clinical measures,"Atrophy of cortical and subcortical gray matter is apparent in Huntington's disease (HD) before symptoms manifest. We hypothesized that the white matter (WM) connecting cortical and subcortical regions must also be affected early and that select clinical symptoms were related to systems degeneration. We used diffusion tensor magnetic resonance imaging (DTI) to examine the regional nature of WM abnormalities in early HD, including the preclinical period, and to determine whether regional changes correlated with clinical features. We studied individuals in early stages (HD), presymptomatic individuals known to carry the genetic mutation that causes HD (Pre-HD), and matched healthy controls. DTI indices of tissue integrity were obtained from several regions of interest, including the corpus callosum (CC), internal capsule (IC), and basal ganglia, were compared across groups by t tests, and were correlated to cognitive and clinical measures. WM alterations were found throughout the CC, in the anterior and posterior limbs of the IC, and in frontal subcortical WM in HD subjects, supporting the selective involvement of the pyramidal tracts in HD; a similar distribution of changes was seen in Pre-HD subjects, supporting presymptomatic alterations. There was a significant relationship between select DTI measures and cognitive performance. Alterations in diffusion indices were also seen in the striatum that were independent of atrophy. Our findings support that WM alterations occur very early in HD. The distribution of the changes suggests that these changes contribute to the disruption of pyramidal and extrapyramidal circuits and also support a role of compromised cortical circuitry in early cognitive and subtle motor impairment during the preclinical stages of HD.","Adult;Atrophy;Basal Ganglia/pathology;Brain/ pathology;Cerebral Cortex/ pathology;Corpus Callosum/pathology;Diffusion Magnetic Resonance Imaging;Early Diagnosis;Extrapyramidal Tracts/pathology;Female;Frontal Lobe/pathology;Humans;Huntington Disease/ diagnosis/genetics;Image Processing, Computer-Assisted;Internal Capsule/pathology;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neural Pathways/ pathology;Neurologic Examination;Neuropsychological Tests;Parietal Lobe/pathology;Pyramidal Tracts/pathology","Rosas, H. D.;Tuch, D. S.;Hevelone, N. D.;Zaleta, A. K.;Vangel, M.;Hersch, S. M.;Salat, D. H.",2006,Sep,10.1002/mds.20979,0,
1621,A tale of two factors: What determines the rate of progression in Huntington's disease? A longitudinal MRI study,"Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1-year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease. © 2011 Movement Disorder Society.",,"Rosas, H. D.;Reuter, M.;Doros, G.;Lee, S. Y.;Triggs, T.;Malarick, K.;Fischl, B.;Salat, D. H.;Hersch, S. M.",2011,1,,0,
1622,"Altered white matter microstructure in the corpus callosum in Huntington's disease: implications for cortical ""disconnection""","The corpus callosum (CC) is the major conduit for information transfer between the cerebral hemispheres and plays an integral role in relaying sensory, motor and cognitive information between homologous cortical regions. The majority of fibers that make up the CC arise from large pyramidal neurons in layers III and V, which project contra-laterally. These neurons degenerate in Huntington's disease (HD) in a topographically and temporally selective way. Since any focus of cortical degeneration could be expected to secondarily de-afferent homologous regions of cortex, we hypothesized that regionally selective cortical degeneration would be reflected in regionally selective degeneration of the CC. We used conventional T1-weighted, diffusion tensor imaging (DTI), and a modified corpus callosum segmentation scheme to examine the CC in healthy controls, huntingtin gene-carriers and symptomatic HD subjects. We measured mid-sagittal callosal cross-sectional thickness and several DTI parameters, including fractional anisotropy (FA), which reflects the degree of white matter organization, radial diffusivity, a suggested index of myelin integrity, and axial diffusivity, a suggested index of axonal damage of the CC. We found a topologically selective pattern of alterations in these measures in pre-manifest subjects that were more extensive in early symptomatic HD subjects and that correlated with performance on distinct cognitive measures, suggesting an important role for disrupted inter-hemispheric transfer in the clinical symptoms of HD. Our findings provide evidence for early degeneration of commissural pyramidal neurons in the neocortex, loss of cortico-cortical connectivity, and functional compromise of associative cortical processing.","Adult;Corpus Callosum/ pathology;Female;Humans;Huntington Disease/ pathology;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology","Rosas, H. D.;Lee, S. Y.;Bender, A. C.;Zaleta, A. K.;Vangel, M.;Yu, P.;Fischl, B.;Pappu, V.;Onorato, C.;Cha, J. H.;Salat, D. H.;Hersch, S. M.",2010,Feb 15,10.1016/j.neuroimage.2009.10.015,0,
1623,Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis,"BACKGROUND: Most clinical symptoms of Huntington disease (HD) have been attributed to striatal degeneration, but extrastriatal degeneration may play an important role in the clinical symptoms because postmortem studies demonstrate that almost all brain structures atrophy. OBJECTIVE: To fully characterize the morphometric changes that occur in vivo in HD. METHODS: High-resolution 1.5 mm T1-weighted coronal scans were acquired from 18 individuals in early to mid-stages of HD and 18 healthy age-matched controls. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour-mapping algorithm. General linear models for correlated data of the volumes of brain regions were used to compare groups, controlling for age, education, handedness, sex, and total brain volumes. RESULTS: Subjects with HD had significant volume reductions in almost all brain structures, including total cerebrum, total white matter, cerebral cortex, caudate, putamen, globus pallidus, amygdala, hippocampus, brainstem, and cerebellum. CONCLUSIONS: Widespread degeneration occurs in early to mid-stages of HD, may explain some of the clinical heterogeneity, and may impact future clinical trials.",Adult;Atrophy;Brain/*pathology;Case-Control Studies;Female;Humans;Huntington Disease/*pathology;*Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration;Time Factors,"Rosas, H. D.;Koroshetz, W. J.;Chen, Y. I.;Skeuse, C.;Vangel, M.;Cudkowicz, M. E.;Caplan, K.;Marek, K.;Seidman, L. J.;Makris, N.;Jenkins, B. G.;Goldstein, J. M.",2003,May 27,,0,
1624,Psychomotor speed and functional brain MRI 2 years after completing a physical activity treatment,"BACKGROUND: Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities. METHODS: We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders-pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from 10 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and 10 SA participants. RESULTS: Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of self-reported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities. CONCLUSIONS: Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis.","Brain [physiology];Follow-Up Studies;Magnetic Resonance Imaging;Mathematics;Motor Activity [physiology];Neuropsychological Tests;Psychomotor Performance;Single-Blind Method;Time Factors;Walking [physiology];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Rosano, C.;Venkatraman, V. K.;Guralnik, J.;Newman, A. B.;Glynn, N. W.;Launer, L.;Taylor, C. A.;Williamson, J.;Studenski, S.;Pahor, M.;Aizenstein, H.",2010,,,0,
1625,"Slower gait, slower information processing and smaller prefrontal area in older adults","Background: slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests. Hypothesis: we hypothesise that slower information processing explains this association, while tests of language or memory will not. Methods: data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index). Results: in linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association. Conclusions: we conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait. © The Author 2011. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.",,"Rosano, C.;Studenski, S. A.;Aizenstein, H. J.;Boudreau, R. M.;Longstreth Jr, W. T.;Newman, A. B.",2012,,,0,
1626,Coronary artery calcium: Associations with brain magnetic resonance imaging abnormalities and cognitive status,"OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/ mild cognitive impairment). DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults. PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS. MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status. RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status. CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status. © 2005 by the American Geriatrics Society.",,"Rosano, C.;Naydeck, B.;Kuller, L. H.;Longstreth Jr, W. T.;Newman, A. B.",2005,April,,0,
1627,High blood pressure accelerates gait slowing inwell-functioning older adults over 18-years of follow-up,"OBJECTIVES: To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it. DESIGN: Longitudinal cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57% female, 15% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included. MEASUREMENTS: Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors. RESULTS: Higher systolic",,"Rosano, C.;Longstreth Jr, W. T.;Boudreau, R.;Taylor, C. A.;Du, Y.;Kuller, L. H.;Newman, A. B.",2011,March,,0,
1628,Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults,"OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance. DESIGN: Longitudinal analysis, average follow-up time: 4.0 years. SETTING: Cardiovascular Health Study (CHS). PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n = 2,450, mean age = 74.4). MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand). RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed. CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance. © 2005 by the American Geriatrics Society.",,"Rosano, C.;Kuller, L. H.;Chung, H.;Arnold, A. M.;Longstreth Jr, W. T.;Newman, A. B.",2005,April,,0,
1629,Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults,"BACKGROUND: Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known. HYPOTHESIS: A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia. METHODS: Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, N = 10, age: 74.9 years, 7 women) or health education (HE, N = 16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus, and cornu ammonis were measured at baseline and at 24-month follow-up using 7-Tesla magnetic resonance imaging. Between-group volumetric differences at 24 months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities, and brain atrophy. RESULTS: Between-group differences were significant for left hippocampus, left cornu ammonis, and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically nonsignificant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors. CONCLUSIONS: In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults.","Aged;Aged, 80 and over;Exercise/ physiology;Exercise Therapy/ methods;Female;Health Education/methods;Hippocampus/ diagnostic imaging;Humans;Magnetic Resonance Imaging;Male;Sedentary Lifestyle;Time Factors;Hippocampal;mobility;physical activity;ultra high field","Rosano, C.;Guralnik, J.;Pahor, M.;Glynn, N. W.;Newman, A. B.;Ibrahim, T. S.;Erickson, K.;Cohen, R.;Shaaban, C. E.;MacCloud, R. L.;Aizenstein, H. J.",2017,Mar,,0,1630
1630,Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults,"Background: Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known. Hypothesis: A long-term moderate intensity regimen of PA is related to larger volume of the hippocampus in older adults at risk for mobility disability. We further explore whether these associations are modified by factors known to be related to dementia. Methods: Twenty-six sedentary adults at risk for mobility disability participated in a 24-month randomized intervention program of physical activity (PA, N = 10, age: 74.9 years, 7 women) or health education (HE, N = 16, age: 76.8 years, 14 women). Volumes of total hippocampus, dentate gyrus, and cornu ammonis were measured at baseline and at 24-month follow-up using 7-Tesla magnetic resonance imaging. Between-group volumetric differences at 24 months were adjusted for sessions attended and baseline volumes. The contribution of each dementia-related factor was tested separately for education, APOE, diabetes, cardiovascular diseases, white matter hyperintensities, and brain atrophy. Results: Between-group differences were significant for left hippocampus, left cornu ammonis, and right hippocampus. Adjustment for regional baseline volume attenuated the associations to statistically nonsignificant for right hippocampus and left conru ammonis; associations for left hippocampus were robust for all adjustments. Results were similar after adjustment for dementia-related factors. Conclusions: In this group of sedentary older adults there was a hippocampal response to a long-term program of moderate-intensity PA. Future studies should examine whether hippocampal response could explain the beneficial effects of PA on cognition for vulnerable older adults. Copyright 2016.",adult;aged;brain atrophy;cardiovascular disease;clinical article;cognition;controlled clinical trial;controlled study;dementia;dentate gyrus;diabetes mellitus;female;follow up;health education;human;left hippocampus;male;nuclear magnetic resonance imaging;physical activity;randomized controlled trial;right hippocampus;walking difficulty;white matter;apolipoprotein E;endogenous compound,"Rosano, C.;Guralnik, J.;Pahor, M.;Glynn, N. W.;Newman, A. B.;Ibrahim, T. S.;Erickson, K.;Cohen, R.;Shaaban, C. E.;MacCloud, R. L.;Aizenstein, H. J.",2017,,,0,
1631,Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults,"Background: Gait variability is an index of how much gait parameters, such as step length, change from one step to the next. Gait variability increases with age and in individuals affected by cortical and subcortical neurodegenerative conditions, and it is associated with falls and incident mobility disability. The brain anatomical correlates of gait variability have not been studied in high-functioning community-dwelling older adults. Methods: Gait variability and brain MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free from stroke, dementia or Parkinson's disease. Gait variability was computed for spatial parameters (step length and step width) and for temporal parameters (stance time). Subclinical brain vascular abnormalities were measured on brain MRIs as infarcts and white matter hyperintensities. Results: Greater variability of step length was associated with greater prevalence of infarcts, including infarcts in the basal ganglia, and with greater white matter hyperintensities severity, independent of age, gender, cognitive function and cardiovascular disease. Weaker associations were found between the other variability measures and the MRI measures. Conclusion: In this group of older adults free from neurodegenerative diseases, a greater variability of step length was associated with greater burden of subclinical brain vascular abnormalities as defined by MRI. Copyright © 2007 S. Karger AG.",aged;article;basal ganglion;brain infarction;cardiovascular disease;cerebrovascular accident;cognition;diagnostic accuracy;diagnostic test;disease severity;female;gait;human;major clinical study;male;medical assessment;neuroimaging;nuclear magnetic resonance imaging;sample size;senescence;white matter,"Rosano, C.;Brach, J.;Studenski, S.;Longstreth Jr, W. T.;Newman, A. B.",2007,,,0,
1632,Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults,"Abnormal gait in high-functioning older adults may indicate underlying subtle structural brain abnormalities. We tested the hypothesis that temporal and spatial parameters of gait, including speed, stride length and double support time, are cross-sectionally associated with white matter hyperintensity, subcortical infarcts or brain atrophy on brain MRI. We examined 321 men and women (mean age = 78.3) participating to the Cardiovascular Health Study who were free of dementia or stroke at the time of the gait assessment. Analyses were set with gait as independent variable and brain MRIs as dependent variables. Gait measures were determined from the footfalls recorded on a 4-meter-long instrumented walking surface, the GaitMat II. Brain MRIs were examined for the presence of white matter hyperintensity (WMG, graded from 0 to 9), brain infarcts (predominantly subcortical) and ventricular enlargement (graded from 0 to 9). Slower gait, shorter stride length and longer double support times were associated with greater prevalence of white matter grade > or =3 (p = 0.02), and at least 1 brain infarct (p = 0.04) independent of age. In multivariate logistic regression models adjusted for demographics and clinical cardiovascular diseases, those with gait speed <1.02 m/s were more likely to have WMG > or =3 and at least 1 brain infarct, compared with those with faster gait - odds ratio (OR): 2.85, 95% confidence interval (95% CI): 1.35, 6.02, and OR: 2.09, 95% CI: 1.04, 4.19. Shorter stride length was also associated with greater probability of having at least 1 brain infarct (gait stride <0.88 vs. >1.10 m: OR: 3.20, 95% CI: 1.49, 6.88), while longer double support times were associated with a greater probability of having WMG > or =3 (double support time >0.19 vs. <0.14 s: OR: 2.3, 95% CI: 1.1, 4.7) independent of demographics and clinical cardiovascular diseases. Gait parameters were not significantly associated with ventricular grade. In summary, in this group of high-functioning older adults, poorer gait speed, shorter stride and longer double support time are associated with high white matter disease and subclinical strokes.","Aged;Brain/*abnormalities/pathology;Cerebral Infarction/pathology;Cerebral Ventricles/pathology;Cerebrovascular Disorders/complications/epidemiology;Cohort Studies;Dementia/complications/epidemiology;Female;Gait/physiology;Gait Disorders, Neurologic/*diagnosis/epidemiology/etiology;Humans;Hypertension/complications;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Stroke/physiopathology;United States/epidemiology","Rosano, C.;Brach, J.;Longstreth Jr, W. T.;Newman, A. B.",2006,,10.1159/000089240,0,
1633,Focal atrophy and cerebrovascular disease increase dementia risk among cognitively normal older adults,"BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults. METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD. RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions. CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.",Aged;Alzheimer Disease/ etiology/pathology;Analysis of Variance;Atrophy;Cerebrovascular Disorders/ complications/pathology;Cognition;Female;Humans;Logistic Models;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Male;Risk Factors;Temporal Lobe/ pathology;United States,"Rosano, C.;Aizenstein, H. J.;Wu, M.;Newman, A. B.;Becker, J. T.;Lopez, O. L.;Kuller, L. H.",2007,Apr,10.1111/j.1552-6569.2007.00093.x,0,
1634,Neuroimaging differences between older adults with maintained versus declining cognition over a 10-year period,"Background: Maintaining cognitive function protects older adults from developing functional decline. This study aims to identify the neuroimaging correlates of maintenance of higher global cognition as measured by the Modified Mini Mental State Test (3MS) score. Methods: Repeated 3MS measures from 1997-98 through 2006-07 and magnetic resonance imaging with diffusion tensor in 2006-07 were obtained in a biracial cohort of 258 adults free from dementia (mean age 82.9. years, 56% women, 42% blacks). Participants were classified as having shown either maintenance (3MS slope > 0) or decline (3MS slope < 1. SD below the mean) of cognition using linear mixed models. Measures of interest were white matter hyperintensity volume (WMHv) from total brain, volume of the gray matter (GMv) and microstructure (mean diffusivity, MD) for total brain and for brain areas known to be related to memory and executive control function: medial temporal area (hippocampus, parahippocampus and entorhinal cortex), cingulate cortex, dorsolateral prefrontal and posterior parietal cortex. Results: Differences between cognitive maintainers (n = 153) and non-maintainers (n = 107) were significant for GMv of the medial temporal area (35.8%, p = 0.004) and lower",,"Rosano, C.;Aizenstein, H. J.;Newman, A. B.;Venkatraman, V.;Harris, T.;Ding, J.;Satterfield, S.;Yaffe, K.",2012,1,,0,
1635,Longitudinal systolic blood pressure characteristics and integrity of white matter tracts in a cohort of very old black and white adults,"BACKGROUND: We sought to determine which systolic blood pressure (SBP) characteristics are associated with reduced brain integrity and whether these associations are stronger for white or gray matter. We hypothesized that exposure to higher and variable SBP will be associated with lower structural integrity of both gray and white matter. METHODS: Neuroimaging, SBP, and cognition were obtained in 311 community-dwelling adults in 2006-2008 (average age = 83 years; 58% women; 40% black). Antihypertensive medications, SBP, and health-related factors were collected from 1997 to 1998 to time of neuroimaging. SBP values obtained from 1997 to 1998 to time of neuroimaging were used to compute mean; pulse pressure; coefficient of variation; and peak, load, and group-based trajectories. RESULTS: Higher mean SBP was associated with lower white matter integrity in uncinate and superior lateral fasciculi bilaterally, independent of age, stroke history, antihypertensive medication use (odds ratio of having white matter hyperintensities greater than or equal to the median for 10mm Hg of SBP = 10.4, 95% confidence interval = 10.2-10.6, P = 0.0001; standardized beta for fractional anisotropy = -13.54, SE = 4.58, P = 0.003). These neuroimaging markers attenuated the association between higher SBP and lower digit symbol substitution test. Results were similar for trajectories of SBP and stronger for those with previously higher and variable SBP even if SBP was normal at neuroimaging. Results were similar for those without stroke. Associations with gray matter measures were not significant. CONCLUSIONS: If confirmed, these data suggest a history of higher and variable SBP for very old adults may be useful to alert clinicians to potential lower integrity in selected tracts, whereas cross-sectional SBP measurements may obscure the risk of underlying white matter hyperintensities. Whether lowering and/or stabilizing SBP levels in very old adults without a remarkable cardiovascular history would have neuroprotective effects and reduce dementia risk needs further study.","Aged, 80 and over;Antihypertensive Agents/therapeutic use;Blood Pressure;Female;Gray Matter/ pathology;Humans;Hypertension/drug therapy/ pathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;White Matter/ pathology","Rosano, C.;Abebe, K. Z.;Aizenstein, H. J.;Boudreau, R.;Jennings, J. R.;Venkatraman, V.;Harris, T. B.;Yaffe, K.;Satterfield, S.;Newman, A. B.",2015,Mar,10.1093/ajh/hpu134,0,
1636,Insular atrophy at the prodromal stage of dementia with Lewy bodies: a VBM DARTEL study,"Diffuse atrophy including the insula was previously demonstrated in dementia with Lewy bodies (DLB) patients but little is known about the prodromal stage of DLB (pro-DLB). In this prospective study, we used SPM8-DARTEL to measure gray matter (GM) and white matter (WM) atrophy in pro-DLB patients (n = 54), prodromal Alzheimer's disease (pro-AD) patients (n = 16), DLB patients at the stage of dementia (mild-DLB) (n = 15), and Alzheimer's disease patients at the stage of dementia (mild-AD) (n = 28), and compared them with healthy elderly controls (HC, n = 22). Diminished GM volumes were found in bilateral insula in pro-DLB patients, a trend to significance in right hippocampus and parahippocampal gyrus in pro-AD patients, in left insula in mild-DLB patients, and in medial temporal lobes and insula in mild-AD patients. The comparison between prodromal groups did not showed any differences. The comparison between groups with dementia revealed atrophy around the left middle temporal gyrus in mild-AD patients. Reduced WM volume was observed in mild-DLB in the pons. The insula seems to be a key region in DLB as early as the prodromal stage. MRI studies looking at perfusion, and functional and anatomical connectivity are now needed to better understand the role of this region in DLB.",,"Roquet, D.;Noblet, V.;Anthony, P.;Philippi, N.;Demuynck, C.;Cretin, B.;Martin-Hunyadi, C.;Loureiro de Sousa, P.;Blanc, F.",2017,Aug 25,,0,
1637,N-tert-butyl-alpha-phenylnitrone reduces the number of microinfarctions in the rabbit brain cortex,"Dementia due to cerebral ischemic lesions is relatively common in the elderly. Since many of these lesions are probably caused by emboli, studying emboli-induced cerebral lesions in rabbits should, hopefully, provide information that is useful when searching for a means of preventing and treating vascular dementia in humans. Using magnetic resonance imaging we have found that N-tert-butyl-alpha-phenyl-nitrone (a free radical scavenger) reduced the number of emboli-induced cerebral microinfarctions in the rabbit cortex but did not have any impact on the number of infarctions found in the subcortical structures. The results suggest that significant amount of free radicals are produced in the ischemic foci located in the cortex, but not in the ischemic foci located in the subcortical structures. This finding may be of importance when considering treatments for cerebral ischemia in humans.",Animals;Brain Ischemia/diagnosis/drug therapy/prevention & control;Cerebral Cortex/blood supply/ pathology;Cerebral Infarction/diagnosis/ drug therapy/ prevention & control;Cerebrovascular Circulation/drug effects;Cyclic N-Oxides;Female;Intracranial Embolism and Thrombosis/diagnosis/drug therapy/prevention & control;Magnetic Resonance Imaging;Male;Microcirculation/drug effects;Nitrogen Oxides/ pharmacology;Rabbits,"Roos, M. W.;Ericsson, A.",1999,Jan,,0,
1638,Fabry's disease revealed by stroke: A case report,We report a 35-year-old man with a stroke as the presenting feature of Fabry's disease. Cerebrovascular manifestation can be the first manifestation of this disease and must be systematically evoked by the neurologist. The neurological follow-up of these patients must be systematic. © 2010 Elsevier Masson SAS.,adult;article;brain ischemia;case report;dementia;Fabry disease;follow up;human;male;neurologic examination;nuclear magnetic resonance imaging,"Ronzière, T.",2010,,,0,
1639,Association of matrix metalloproteinases with MRI indices of brain ischemia and aging,"Magnetic resonance imaging (MRI) findings of large white matter hyperintensities (LWMH), decreased brain volume and silent cerebral infarcts (SCI) are subclinical indices of brain ischemia and aging. Although the pathophysiology of these findings remains uncertain, extracellular matrix (ECM) remodeling, a process regulated by matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), may be implicated. We evaluated the cross-sectional relations of circulating MMP-9 and TIMP-1 to these MRI indices in 583 stroke and dementia-free, Framingham Offspring participants (mean age 57 years, 58% women). Using multivariable regression MMP-9 (detectable versus non-detectable) and TIMP-1 (modeled as sex-specific quartiles) were related to LWMH (>1S.D. above age-specific mean; yes/no), SCI (yes/no) and total brain volume (ratio of parenchymal to intracranial volume, TCBVr). Mean TCBVr was 0.78 (S.D. 0.03), 13% of subjects had LWMH and 12% had SCI. Detectable MMP-9 was associated with higher prevalence of LWMH (OR 2.09, 95%confidence interval (CI) 1.00-4.37), but not with TCBVr. TIMP-1 was associated with a high prevalence of LWMH (OR for Q4 versus Q1-3: 1.83, 95%CI 1.06-3.18) and with lower mean TCBVr (Q4 associated with 0.17 S.D. units lower value relative to Q1-3; p=0.04). Neither biomarker was associated with SCI. Our findings are preliminary but if confirmed in further studies, suggest a pathophysiological role for the MMP/TIMP pathway in processes of brain ischemia and aging.",Aged;Aging/ metabolism/ pathology;Atrophy;Biomarkers/metabolism;Brain Infarction/diagnosis/enzymology/pathology;Brain Ischemia/diagnosis/ enzymology/ pathology;Cross-Sectional Studies;Extracellular Matrix/enzymology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Matrix Metalloproteinase 9/metabolism;Matrix Metalloproteinases/ metabolism;Middle Aged;Tissue Inhibitor of Metalloproteinase-1/metabolism,"Romero, J. R.;Vasan, R. S.;Beiser, A. S.;Au, R.;Benjamin, E. J.;DeCarli, C.;Wolf, P. A.;Seshadri, S.",2010,Dec,10.1016/j.neurobiolaging.2008.11.004,0,
1640,Lipoprotein phospholipase A2 and cerebral microbleeds in the Framingham Heart Study,"BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) attributable to cerebral amyloid angiopathy generally occur in lobar regions, whereas those attributable to hypertensive vasculopathy are deep. Inflammation may be an underlying mechanism for CMB, with varying associations according to CMB location. Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular inflammation associated with risk of ischemic stroke and dementia. We hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of CMB, with possible regional specificity. METHODS: Framingham Offspring participants aged 65 years or older with available Lp-PLA2 measures and brain magnetic resonance imaging were included. Logistic regression models were used to relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex, medication use (aspirin, anticoagulants, and statins), systolic blood pressure, APOE, current smoking, and diabetes. RESULTS: Eight-hundred nineteen participants (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were lobar, and 27 (3%) were deep. We did not observe significant associations of CMB and LpPLA2 measures in multivariable adjusted analyses. However, there was a significant interaction between APOE genotype and Lp-PLA2 activity in their relation to presence of deep CMB (P interaction=0.01). Among persons with APOE epsilon3/epsilon3, the odds ratio for deep CMB was 0.95 (confidence interval, 0.59-1.53; P=0.83), whereas among those with at least 1 epsilon2 or epsilon4 allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006). CONCLUSIONS: In our community-based sample of older adults, there was no significant association of Lp-PLA2 with total or lobar CMB. The association of higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE epsilon2 or epsilon4 allele merits replication.",Aged;Apolipoprotein E2/genetics;Apolipoprotein E4/genetics;Cerebral Hemorrhage/blood/ enzymology/genetics;Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Phospholipases A2/ blood,"Romero, J. R.;Preis, S. R.;Beiser, A. S.;DeCarli, C.;Lee, D. Y.;Viswanathan, A.;Benjamin, E. J.;Fontes, J.;Au, R.;Pikula, A.;Wang, J.;Kase, C. S.;Wolf, P. A.;Irrizary, M. C.;Seshadri, S.",2012,Nov,10.1161/strokeaha.112.656744,0,
1641,Cerebral Microbleeds as Predictors of Mortality: The Framingham Heart Study,"BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) represent a common magnetic resonance imaging marker of cerebral small vessel disease, increasingly recognized as a subclinical marker of stroke and dementia risk. CMB detection may reflect the cumulative effect of vascular risk burden and be a marker of higher mortality. We investigated the relation of CMB to risk of death in community dwelling participants free of stroke and dementia. METHODS: We evaluated 1963 Framingham Original and Offspring Cohort participants (mean age 67 years; 54% women) with available brain magnetic resonance imaging and mortality data. Using Cox proportional hazards models, we related CMB to all-cause, cardiovascular, and stroke-related mortality. RESULTS: Participants with CMB (8.9%) had higher prevalence of cardiovascular risk factors and use of preventive medications. During a mean follow-up of 7.2+/-2.6 years, we observed 296 deaths. In age- and sex-adjusted analysis, CMB were associated with increased all-cause mortality (hazards ratio, 1.39; 95% confidence interval 1.03-1.88), a relation that was no longer significant after adjustment for cardiovascular risk and preventive medication use (hazards ratio, 1.15; 95% confidence interval, 0.82-1.63). CONCLUSIONS: CMBs may represent the deleterious effect of cardiovascular risk factors in the cerebral vasculature. Although their presence was associated with increased all-cause mortality, the effect was no longer present after accounting for vascular risk factors and preventive treatment use. Further studies are required to clarify the role of cardiovascular preventive therapies for prevention of mortality in persons with incidental detection of CMB.",cerebral microbleed;cerebral small vessel disease;community;epidemiology,"Romero, J. R.;Preis, S. R.;Beiser, A.;Himali, J. J.;Shoamanesh, A.;Wolf, P. A.;Kase, C. S.;Vasan, R. S.;DeCarli, C.;Seshadri, S.",2017,Mar,,1,
1642,"Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study","BACKGROUND AND PURPOSE: Carotid atherosclerosis has been associated with increased risk of stroke and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear. METHODS: We studied 1975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI, and neuropsychological testing. We related common and internal carotid artery intima-media thickness and internal carotid stenosis to large white matter hyperintensity (>1 SD above age-specific mean), total brain volume, hippocampal volume, silent cerebral infarcts, and neuropsychological measures of verbal memory, executive function, and nonverbal memory measures. RESULTS: We observed that internal carotid artery intima-media thickness, but not common carotid artery intima-media thickness, was associated with higher prevalence of silent cerebral infarcts (OR, 1.21; 95% CI, 1.03-1.43; P<0.05), large white matter hyperintensity (OR, 1.19; 95% CI, 1.03-1.38; P<0.05), lower total brain volume (-0.05 per SD; P<0.05), and poorer performance in verbal memory (-0.06 per SD; P<0.05) and nonverbal memory measures (-0.08 per SD; P<0.01), but not with hippocampal volume. Internal carotid stenosis >or=25% was associated with a higher prevalence of large white matter hyperintensity (adjusted OR, 1.77; 95% CI, 1.25-2.53) and lower total brain volume (-0.11 per SD; P=0.042) but not with silent cerebral infarcts or hippocampal volume. Internal carotid stenosis >or=50% was associated with higher prevalence of silent cerebral infarcts (OR, 2.53; 95% CI, 1.17-5.44), large white matter hyperintensity (OR, 2.35; 95% CI, 1.08-5.13), and poorer performance on executive function (-0.39 per SD; P<0.05), but not with total brain volume or hippocampal volume. CONCLUSIONS: Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that internal carotid artery intima-media thickness may be a better marker for cognitive impairment than common carotid artery intima-media thickness.","Aged;Aging/physiology;Atherosclerosis/*complications/pathology/*psychology;Brain/pathology;Brain Ischemia/*complications/pathology/*psychology;Carotid Arteries/pathology;Carotid Artery Diseases/*complications/pathology/*psychology;Carotid Artery, Common/pathology/ultrasonography;Carotid Artery, Internal/pathology/ultrasonography;Carotid Stenosis/pathology/ultrasonography;Cognition Disorders/etiology/*psychology;Female;Humans;Magnetic Resonance Imaging;Male;Memory/physiology;Neuropsychological Tests;Psychomotor Performance/physiology;Regression Analysis;Risk Factors","Romero, J. R.;Beiser, A.;Seshadri, S.;Benjamin, E. J.;Polak, J. F.;Vasan, R. S.;Au, R.;DeCarli, C.;Wolf, P. A.",2009,May,10.1161/strokeaha.108.535245,0,
1643,Cerebral microbleeds and risk of incident dementia: the Framingham Heart Study,"Cerebral microbleeds (CMBs) are MRI markers attributed to the most common cerebral angiopathies in the elderly and in patients with dementia: hypertensive and cerebral amyloid angiopathy. CMB detection in asymptomatic persons may help identify those at risk for dementia and may influence preventive strategies and design of clinical trials testing treatments for dementia. We studied the association of CMB with risk of incident dementia in community dwelling individuals. A total of 1296 dementia-free Framingham Heart Study participants (mean age 72 years; 54% women) with available brain MRI and incident dementia data during a mean follow-up period of 6.7 years were included. Using Cox proportional hazards models, we related CMB presence to incident dementia. Multivariable models were adjusted for age, sex, APOE status, and education, with additional models adjusting for vascular risk factors and MRI markers of ischemic brain injury. CMBs were observed in 10.8% and incident dementia in 85 participants (6.6% over study period). Participants with any CMB had 1.74 times higher risk of dementia (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.00-3.01), whereas those with deep and mixed CMB had a three-fold increased risk (HR 2.99, 95% CI 1.52-5.90). The associations were independent of vascular risk factors, and for deep and mixed CMB also independent of MRI markers of ischemia (HR 2.44, 95% CI 1.22-4.88). Purely lobar CMBs were not associated with incident dementia. Our findings support a role for hypertensive vasculopathy and the interplay of hypertensive and cerebral amyloid angiopathy in risk of dementia and suggest that CMB presence can identify individuals at risk of dementia.",Brain MRI;Cerebral microbleeds;Cerebral small vessel disease;Dementia,"Romero, J. R.;Beiser, A.;Himali, J. J.;Shoamanesh, A.;DeCarli, C.;Seshadri, S.",2017,Mar 06,,0,
1644,Senile dementia of the Binswanger type. A vascular form of dementia in the elderly,"Computed tomography and magnetic resonance imaging in the elderly have demonstrated the common occurrence of deep white-matter lesions in the aging brain. These radiologic lesions (leukoaraiosis) may represent an early marker of dementia. At autopsy, an ischemic periventricular leukoencephalopathy (Binswanger's disease) has been found in most cases. The clinical spectrum of Binswanger's disease appears to range from asymptomatic radiologic lesions to dementia with focal deficits, frontal signs, pseudobulbar palsy, gait difficulties, and urinary incontinence. The name senile dementia of the Binswanger type (SDBT) is proposed for this poorly recognized, vascular form of subcortical dementia. The SDBT probably results from cortical disconnection most likely caused by hypoperfusion. In contrast, multi-infarct dementia is correlated with multiple large and small strokes that cause a loss of over 50 to 100 mL of brain volume. The periventricular white matter is a watershed area irrigated by long, penetrating medullary arteries. Risk factors for SDBT are small-artery diseases, such as hypertension and amyloid angiopathy, impaired autoregulation of cerebral blood flow in the elderly, and periventricular hypoperfusion due to cardiac failure, arrhythmias, and hypotension. The SDBT may be a potentially preventable and treatable form of dementia.","Aged;Cerebral Arterial Diseases/ complications/pathology;Dementia/ diagnosis/etiology/physiopathology;Humans;Magnetic Resonance Spectroscopy;Tomography, X-Ray Computed","Roman, G. C.",1987,Oct 2,,0,
1645,The identity of lacunar dementia and Binswanger disease,"It is postulated here that the dementia occurring in patients with lacunar strokes is due to an ischemic leukoencephalopathy. Severity of the dementia correlates, not with the volume of brain tissue lost from large-artery infarctions, but rather, with the extent of cortex disconnection resulting from demyelination. The term Lacunar Dementia is proposed, instead of the poorly known eponym ""Binswanger disease"" or the cumbersome descriptive name ""subcortical arteriosclerotic encephalopathy."" Clinically, Lacunar Dementia presents with gait difficulties, urinary incontinence, parkinsonian features, pseudobulbar palsy, emotional incontinence and dementia. High-resolution CT scan shows decrease density of frontal and periventricular white matter, without contrast enhancement; ventricular dilation, and lacunar infarcts. Small-artery disease lipohyalinosis is the cause of the lacunes and the leukoencephalopathy. Since the advent of the high-resolution CT scan, the frequency of lacunar dementia seems to be increasing, in contrast with the number of cases of multi-infarct dementia.",Cerebral Cortex/pathology;Dementia/diagnosis/*pathology;Humans;Myelin Sheath/pathology;Syndrome;Telencephalon/*pathology;Terminology as Topic,"Roman, G. C.",1985,Apr,,0,
1646,Reasons that prevent the inclusion of Alzheimer's disease patients in clinical trials,"AIM: To assess reasons that prevent Alzheimer's disease (AD) patients from being included in clinical trials. METHODS: In 2009, we reviewed the Lille Memory Clinic's case database to identify patients suitable for inclusion in four AD clinical trials. An initial selection was made on the basis of four criteria: (i) a diagnosis of AD (with or without white matter lesions [WML]), (ii) age, (iii) mini mental state examination (MMSE) score and (iv) symptomatic treatment of AD (cholinesterase inhibitors/memantine). Next, data on patients fulfilling these criteria were reviewed against all the inclusion/exclusion criteria for four clinical trials performed in 2009 at the Memory Clinic. Reasons for non-inclusion were analyzed. RESULTS: Two hundred and five patients were selected according to the four initial criteria. Reasons for subsequently not including some of patients in clinical trials were abnormalities on MRI (56.9%, 88.9% of which were WML), unauthorized medication (37.3%), the lack of a study partner/informant (37.1%), the presence of a non-authorized disease (24.4%), contraindication to MRI (9%), a change in diagnosis over time (3.9%), visual/auditory impairments (2.9%), alcohol abuse (2%) and an insufficient educational level (1%). CONCLUSION: A high proportion of AD patients presented with vascular abnormalities on MRI. This was not unexpected, since the patients were selected from the database and, as shown in epidemiologic studies, cerebrovascular diseases are frequently associated with AD. The presence of a study partner is essential for enabling a patient to participate in clinical trials because of the need to record reliably primary and secondary outcomes.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis;Double-Blind Method;Humans;Middle Aged;*Patient Selection;Randomized Controlled Trials as Topic/*standards","Rollin-Sillaire, A.;Breuilh, L.;Salleron, J.;Bombois, S.;Cassagnaud, P.;Deramecourt, V.;Mackowiak, M. A.;Pasquier, F.",2013,Apr,10.1111/j.1365-2125.2012.04423.x,0,
1647,Lymphomatosis cerebri as a cause of white matter dementia,"Primary central nervous system lymphoma most often presents as a solitary, isolated lesion in immunocompetent patients. Rarely, the disease presents as a diffuse, infiltrating condition without formation of a cohesive mass, a pattern called lymphomatosis cerebri. We present 3 immunocompetent individuals who developed rapidly progressive dementia. Magnetic resonance imaging features mimicked other disorders of white matter and prompted preoperative diagnoses of Binswanger's disease (subcortical ischemic vascular dementia), unknown leukoencephalopathy, viral infection, or infiltrating glioma. Neuropathologic examination at biopsy (Poon T, Matoso I, Tchertkoff V, Weitzner I Jr, Gade M. CT features of primary cerebral lymphoma in AIDS and non-AIDS patients. J Comput Assist Tomogr. 1989;13:6-9) and autopsy (Schwaighofer BW, Hesselink JR, Press GA, Wolf RL, Healy ME, Berthoty DP. Primary intracranial CNS lymphoma: MR manifestations. Am J Neuroradiol. 1993;10:725-9) demonstrated nonnecrotic, diffusely infiltrating, large-cell B-cell lymphoma of white matter, with relative sparing of gray matter, and without significant leptomeningeal involvement or bulky periventricular disease at autopsy. Microglial and astrocytic reactions, but only subtle myelin pallor, were evident as individual tumor cells permeated the entire brain and spinal cord, albeit with considerable variation in cell density. Individual tumor cells could be identified from the optic nerve to spinal cord, documenting the ""whole-brain"" nature of the disease. CD20 immunostaining was necessary to fully appreciate the extent of individual lymphoma cell percolation through the white matter. The neurobehavioral deficits manifested by these patients demonstrate that lymphomatosis cerebri is an additional neoplastic cause of white matter dementia and can be added to the growing list of disorders responsible for this syndrome. © 2005 Elsevier Inc. All rights reserved.",,"Rollins, K. E.;Kleinschmidt-Demasters, B. K.;Corboy, J. R.;Damek, D. M.;Filley, C. M.",2005,March,,0,
1648,A SPECT study of wandering behavior in Alzheimer's disease,"BACKGROUND: Among behavior disturbance during Alzheimer's disease (AD), wandering is one of the most common. Different psychological processes have been suggested to explain the wandering behavior. The aim of this study was to examine whether wandering during AD was associated with cerebral perfusion patterns measured by (99 m)Tc-labeled bicisate (ECD) brain SPECT. METHODS: We compared SPECT scans of 13 AD subjects with wandering behavior (sex ratio M/F, 4/9; age, 73.1 years, SD 7.4; Mini Mental Status Examination score, median 20 interquartile range [16-23]), 13 AD subjects without wandering behavior (matched for age [ +/- 2 years], sex and MMSE score [ +/- 2 points]) and 13 healthy controls (matched for age [ +/- 2 years] and sex) without cognitive impairment. Wandering was defined on the Neuro-Psychiatric Inventory. Score of leukoaraiosis, assessed with the scale of Blennow and number of lacuna infarction were compared on CT scan. SPECT imaging was compared using statistical parametric mapping (SPM 2). RESULTS: There were no significant differences between the groups in term of educational level and CT scan analysis. SPECT imaging was consistent with the diagnosis of AD in both wanderers and AD subjects without wandering behavior. Despite similar clinical dementia severity, wanderers had more severely reduced regional cerebral blood flow (rCBF) in the left parietal-temporal lobe than AD subjects without wandering behavior. CONCLUSION: Wandering behavior could be facilitated by a specific patterns of cerebral blood flow. Wandering, as a physical activity, could also enhance the recruitment of the cortical network.","Aged;Aged, 80 and over;Alzheimer Disease/physiopathology/ psychology/radionuclide imaging;Brain/physiopathology/ radionuclide imaging;Brain Mapping/methods;Cerebrovascular Circulation;Educational Status;Female;Humans;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Psychomotor Agitation/ etiology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Rolland, Y.;Payoux, P.;Lauwers-Cances, V.;Voisin, T.;Esquerre, J. P.;Vellas, B.",2005,Sep,10.1002/gps.1362,0,
1649,Acute cerebrovascular disease in the young: The stroke in young fabry patients study,"BACKGROUND AND PURPOSE - : Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. METHODS - : Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. RESULTS - : Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). CONCLUSIONS - : Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. © 2013 American Heart Association, Inc.",,"Rolfs, A.;Fazekas, F.;Grittner, U.;Dichgans, M.;Martus, P.;Holzhausen, M.;Böttcher, T.;Heuschmann, P. U.;Tatlisumak, T.;Tanislav, C.;Jungehulsing, G. J.;Giese, A. K.;Putaala, J.;Huber, R.;Bodechtel, U.;Lichy, C.;Enzinger, C.;Schmidt, R.;Hennerici, M. G.;Kaps, M.;Kessler, C.;Lackner, K.;Paschke, E.;Meyer, W.;Mascher, H.;Riess, O.;Kolodny, E.;Norrving, B.",2013,February,,0,
1650,Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study,"The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on (18)F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD-) showed brain amyloid positivity. POD+ compared to POD- displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.",Alzheimer's disease;Amyloid;Delirium;Neuroimaging;Surgery,"Rolandi, E.;Cavedo, E.;Pievani, M.;Galluzzi, S.;Ribaldi, F.;Buckley, C.;Cunningham, C.;Guerra, U. P.;Musarra, M.;Morzenti, S.;Magnaldi, S.;Patassini, M.;Terragnoli, F.;Matascioli, L.;Franzoni, S.;Annoni, G.;Carnevali, L.;Bellelli, G.;Frisoni, G. B.",2018,Jan,,0,
1651,Presentation of amyloidosis in carriers of the codon 692 mutation in the amyloid precursor protein gene (APP692),"Several mutations in the amyloid precursor protein (APP) gene may lead to either Alzheimer's disease or cerebral haemorrhage due to congophilic amyloid angiopathy (CAA). A single family is known in which both types of pathology are expressed because of a missense mutation at codon 692 of the APP gene (APP692). Here we describe the clinical and pathological expression of APP692 in eight patients with the mutation. Furthermore, 21 first-degree relatives with an a priori risk of 50% of being a carrier were tested for the APP692 mutation and studied for presymptomatic signs by neurological examination, neuropsychological testing and brain MRI. Patients with APP692 presented with haemorrhage, dementia or both. The dementia in patients with the APP692 mutation was compatible with Alzheimer's disease both clinically and neuropathologically. Of the 21 healthy relatives at 50% risk, five carried the APP692 mutation. The presymptomatic carriers showed a subtle, non-significant impairment of cognitive function compared with relatives without APP692. A significant increase in the number of periventricular and subcortical white matter lesions at young age was seen in presymptomatic carriers (mean age 26.4 years). The findings of this study suggest that a single (genetic) mechanism may underlie the pathology of Alzheimer's disease and CAA. These diseases are manifested subclinically by white matter pathology. Further insight into the relationship between CAA and Alzheimer's disease may provide clues about the aetiology of Alzheimer's disease.",amyloid beta protein;amyloid precursor protein;apolipoprotein E;DNA;adult;Alzheimer disease;article;brain hemorrhage;clinical article;codon;controlled study;family study;female;gene mutation;heterozygote;human;male;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;presenile dementia;priority journal;segregation analysis;vascular amyloidosis,"Roks, G.;Van Harskamp, F.;De Koning, I.;Cruts, M.;De Jonghe, C.;Kumar-Singh, S.;Tibben, A.;Tanghe, H.;Niermeijer, M. F.;Hofman, A.;Van Swieten, J. C.;Van Broeckhoven, C.;Van Duijn, C. M.",2000,,,0,
1652,Daily carnosine and anserine supplementation alters default mode network connectivityand working memory in healthyadults,"Background: Carnosine and Anserine are strong antioxidants, previously demonstrated to reduce cognitive decline in animal studies. Methods: Thirty-two healthy participants (age 40-78, IQR=58-71, 10M/22F) were recruited in Tokyo area. Each participant signed written consent to participate in the study. Exclude criteria was following: 1) those who have a neuropsychiatric disorder or head injury. 2) having local lesions, such as a brain tumor or cerebral infarction, which affects a cognitive function by first-time MRI, are found. 3) having the metal or electrical conductivity is contained, or a problem arises at the time of an MRI image pick-up for claustrophobia. Participants were randomized to twice-daily doses of imidazole dipeptide formula (n=15), including 500 mg in total (Carnosine/Anserine=1/3) from chicken meat (produced by Nippon Meat Packers Inc., Japan), or an identical placebo (n=17) in a double-blinded study. Assignment to dipeptide or placebo was determined by age and gender. Functional MRI (3T Siemens, MAGNETOM Verio) and neuropsychological assessments were carried out at baseline and after 3 months. We analysed resting state fMRI data with the FSL analysis pipeline. Processing steps included the FSLFIX for noise filtering, melodic ICA, dual regression and randomize statistical analysis functions. This study is supported by Scientific technique promotion program for agriculture, forestry, fisheries and food industry, from Ministry of Agriculture, Forestry and Fishery (MAFF), Government of Japan. Results: There were no differences in neuropsychological scores and functional network connectivity between the groups at baseline. After 3 months of supplementation, the Carnosine/Anserine group showed decreased coupling between the default mode network, right fronto-parietal network and vast brain regions, compared with placebo (p<0.01). Additionally, the Carnosine/Anserine group showed less decline in WMS-LMII scores compared with placebo; this was statistically significant for the over-60 age group (n=22) (p=0.01). Conclusions: This is the first human study of the neurocognitive effects of Carnosine/Anserine supplementation. The results indicate that Carnosine/Anserine supplementation may have cognitive benefits, particularly in the more elderly population. Furthermore, changes in resting state functional connectivity may be a potential biomarker or even underlie these cognitive benefits. An expanded study is currently under way.",supplementation;default mode network;working memory;human;Japan;forestry;functional magnetic resonance imaging;fishery;agriculture;nuclear magnetic resonance imaging;cognition;brain infarction;statistical analysis;filtration;food industry;government;electric conductivity;noise;animal experiment;brain tumor;gender;meat;pipeline;processing;head injury;chicken meat;brain region;groups by age;aged;population;diseases;claustrophobia;nuclear magnetic resonance scanner;anserine;carnosine;placebo;dipeptide;metal;antioxidant;nitrogen 15;imidazole;biological marker,"Rokicki, J.;Li, L.;Matsuda, H.;Imabayashi, E.;Hisatsune, T.",2016,,,0,
1653,Reduced white matter integrity of the rostral limbic system pathways in healthy elderlyapoe e4 allele carriers,"Background: It is largely known that Alzheimer's disease (AD) related neurofibrillary tangle formation starts in the subcortical limbic system. We hypothesized that the limbic system may be affected in elderly people carrying the 4 allelic variant of the apolipoproteine gene (apoe4), the best established genetic risk factor for late onset AD. A revised limbic system model has recently provided a white matter tracts-related framework for studying connectivity impairments in AD. Therefore, we investigated the impact of the apoe4 allele on the limbic system network in healthy elderly individuals. Methods: Whole brain deterministic tractography was performed using exploredti (http://www.exploredti.com) on diffusion-weighted images in 28 healthy elderly individuals, 12 apoe4 carriers (apoe4+) and 16 apoe4 non-carriers (apoe4-), from the multicentre European Diffusion Tensor Imaging Study on Dementia (EDSD) database. According to the revised limbic system model for memory, emotion and behaviour [1], the fornix, the posterior cingulum and the anterior thalamic projections were dissected. The dissection of three more tracts will be performed: the anterior cingulum, the whole cingulum and the uncinate. A regions of interest approach was used to carry out the tracts dissection with Trackvis (http://www.trackvis.org). Fractional Anisotropy (FA) and Mean Diffusivity (MD) mean values were extracted for each bundle and compared using Mann Whitney U non-parametric test. Results: apoe4+ and apoe4- were matched by sex, age, education and global cognition. FA values were significantly lower in apoe4+ compared to the apoe4- in the right anterior thalamic projections (mean: 0.39, SD 0.035 and mean: 0.41, SD 0.028 respectively; p = 0.038). No significant effect was found for the MD measures in all tracts considered. Conclusions: FA reduction was found in the tract connecting the prefrontal cortex and the mediodorsal and anterior thalamic nuclei. This may present an indicator of a rostral limbic disconnection in healthy elderly individuals at increased genetic risk for sporadic AD. Further investigation of other rostral limbic pathways such as the uncinate and the anterior cingulum may better explain the specific effect of the apoe4 allele on the limbic system. [1] Catani, Dell'acqua, Thiebaut de Schotten. 2013. A revised limbic system model for memory, emotion and behaviour. Neurosci Biobehav Rev. 37:1724-1737.",aged;Alzheimer disease;behavior;cingulum (brain);clinical article;clinical trial;controlled clinical trial;controlled study;data base;diffusion tensor imaging;disease carrier;disease model;dissection;education;fractional anisotropy;gene frequency;gene inactivation;genetic risk;human;limbic system;memory;multicenter study;nonparametric test;prefrontal cortex;thalamus anterior nucleus;white matter;apolipoprotein E;endogenous compound,"Rojkova, K.;Cavedo, E.;Schotten, M. T.;Lista, S.;Brueggen, K.;Bokde, A. L. W.;Dubois, B.;Barkhof, F.;Pouwels, P. J. W.;Teipel, S. J.;Hampel, H.",2017,,,0,
1654,Higher prevalence of cerebral white matter hyperintensities in homozygous APOE-varepsilon4 allele carriers aged 45-75: Results from the ALFA study,"Cerebral white matter hyperintensities are believed the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease. The varepsilon4 allele of the APOE gene is the major factor accountable for Alzheimer's disease heritability. However, the relationship between white matter hyperintensities and APOE genotype in healthy subjects remains controversial. We investigated the association between APOE-varepsilon4 and vascular risk factors with white matter hyperintensities, and explored their interactions, in a cohort of cognitively healthy adults (45-75 years). White matter hyperintensities were assessed with the Fazekas Scale from magnetic resonance images (575 participants: 74 APOE-varepsilon4 homozygotes, 220 heterozygotes and 281 noncarriers) and classified into normal (Fazekas < 2) and pathological (>/=2). Stepwise logistic regression was used to study the association between pathological Fazekas and APOE genotype after correcting for cardiovascular and sociodemographic factors. APOE-varepsilon4 homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432; 95% CI [1.297-9.082]; p = 0.013) of displaying pathological white matter hyperintensities. As expected, aging, hypertension and cardiovascular and dementia risk scales were also positively associated to pathological white matter hyperintensities, but these did not modulate the effect of APOE-varepsilon4/varepsilon4. In subjects at genetic risk of developing Alzheimer's disease, the control of modifiable risk factors of white matter hyperintensities is of particular relevance to reduce or delay dementia's onset.",Alzheimer's disease;Apolipoprotein E;cerebrovascular;magnetic resonance imaging;risk factors;small vessel disease,"Rojas, S.;Brugulat-Serrat, A.;Bargallo, N.;Minguillon, C.;Tucholka, A.;Falcon, C.;Carvalho, A.;Moran, S.;Esteller, M.;Gramunt, N.;Fauria, K.;Cami, J.;Molinuevo, J. L.;Gispert, J. D.",2018,Feb,,0,
1655,Whole-body distribution and metabolism of N-methyl-11C (R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinolinecarboxamide in humans; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography,"PURPOSE: (11)C-PK11195 is a radiopharmaceutical for in vivo assessment of peripheral benzodiazepine receptor (PBR) activity using PET. We sought to clarify the metabolic fate of (11)C-PK11195 in a test-retest setting using radio-HPLC in comparison with radio-TLC, and the whole-body distribution in humans. MATERIALS AND METHODS: In order to evaluate the reproducibility of radio-HPLC metabolite analyses, ten patients with Alzheimer's disease (AD) underwent two successive (11)C-PK11195 examinations on separate days. For comparison of different analytical methods, plasma samples from seven patients were also analysed by radio-TLC. In addition, we evaluated the whole-body distribution of (11)C-PK11195 and its uptake in the brain. RESULTS: The level of unmetabolized (11)C-PK11195 decreased slowly from 96.3 +/- 1.6% (mean+/-SD) at 5 min to 62.7 +/- 8.3% at 40 min after injection. Large individual variation was observed in the amount of plasma (11)C-PK11195 radiometabolites. The whole-body distribution of (11)C-PK11195 showed the highest radioactivity levels in urinary bladder, adrenal gland, liver, salivary glands, heart, kidneys, and vertebral column. In addition, the hip bone and breast bone were clearly visualized by PET. In patients with AD, (11)C-PK11195 uptake in the brain was the highest in the basal ganglia and thalamus, followed by the cortical grey matter regions and the cerebellum. Low (11)C-PK11195 uptake was observed in the white matter. CONCLUSION: Our results indicate that (11)C-PK11195 is eliminated both through the renal and hepatobiliary systems. Careful analysis of plasma metabolites is required to determine the accurate arterial input function for quantitative PET measurement.","Aged;Aged, 80 and over;Antineoplastic Agents/ pharmacology;Carbon Radioisotopes/ pharmacology;Female;Humans;Isoquinolines/ pharmacology;Male;Middle Aged;Positron-Emission Tomography/ methods;Receptors, GABA-A/ chemistry;Reproducibility of Results;Time Factors;Tissue Distribution;Whole Body Imaging/ methods","Roivainen, A.;Nagren, K.;Hirvonen, J.;Oikonen, V.;Virsu, P.;Tolvanen, T.;Rinne, J. O.",2009,Apr,10.1007/s00259-008-1000-1,0,
1656,Neuroimaging in frontotemporal dementia,"The term frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are associated with atrophy of the frontal and temporal lobes, and present clinically with impairments of behaviour or language. Three main subtypes are described, behavioural variant FTD (bvFTD) and two subtypes of the language presentation (known as primary progressive aphasia or PPA) called semantic variant of PPA and non-fluent variant of PPA. Most imaging studies of FTD have used volumetric T1 magnetic resonance imaging (MRI) or positron emissions tomography imaging to identify patterns of grey matter atrophy or hypometabolism in these different subtypes, but more recently newer imaging techniques have been used to help define abnormalities in structural connectivity (white matter tract integrity using diffusion tensor imaging), functional connectivity (resting state networks using resting state functional MRI) and perfusion (using arterial spin labelling perfusion MRI) in FTD. These techniques have the potential to improve the differential diagnosis of FTD from other disorders and to provide more informative imaging signatures of FTD syndromes. © 2013 Institute of Psychiatry.",,"Rohrer, J. D.;Rosen, H. J.",2013,April,,0,
1657,Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations,"Neural network breakdown is a key issue in neurodegenerative disease, but the mechanisms are poorly understood. Here we investigated patterns of brain atrophy produced by defined molecular lesions in the two common forms of genetically mediated frontotemporal lobar degeneration (FTLD). Nine patients with progranulin (GRN) mutations and eleven patients with microtubule-associated protein tau (MAPT) mutations had T1 MR brain imaging. Brain volumetry and grey and white matter voxel-based morphometry (VBM) were used to assess patterns of cross-sectional atrophy in the two groups. In a subset of patients with longitudinal MRI rates of whole-brain atrophy were derived using the brain-boundary-shift integral and a VBM-like analysis of voxel-wise longitudinal volume change was performed. The GRN mutation group showed asymmetrical atrophy whereas the MAPT group showed symmetrical atrophy. Brain volumes were smaller in the GRN group with a faster rate of whole-brain atrophy. VBM delineated a common anterior cingulate-prefrontal-insular pattern of atrophy in both disease groups. Additional disease-specific profiles of grey and white matter loss were identified on both cross-sectional and longitudinal imaging: GRN mutations were associated with asymmetrical inferior frontal, temporal and inferior parietal lobe grey matter atrophy and involvement of long intrahemispheric association white matter tracts, whereas MAPT mutations were associated with symmetrical anteromedial temporal lobe and orbitofrontal grey matter atrophy and fornix involvement. The findings suggest that the effects of GRN and MAPT mutations are expressed in partly overlapping but distinct anatomical networks that link specific molecular dysfunction with clinical phenotype.","Aged;Atrophy;Brain/ pathology;Brain Mapping;Female;Frontotemporal Lobar Degeneration/ genetics/ pathology;Genotype;Humans;Image Interpretation, Computer-Assisted;Intercellular Signaling Peptides and Proteins/ genetics;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Phenotype;tau Proteins/ genetics","Rohrer, J. D.;Ridgway, G. R.;Modat, M.;Ourselin, S.;Mead, S.;Fox, N. C.;Rossor, M. N.;Warren, J. D.",2010,Nov 15,10.1016/j.neuroimage.2009.12.088,0,
1658,Progressive logopenic/phonological aphasia: erosion of the language network,"The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. Five of nine patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings is threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.","Aged;Alzheimer Disease/pathology;Aphasia, Primary Progressive/*pathology/psychology;Brain/*pathology;Cerebral Cortex/pathology;Cognition/physiology;Dementia/pathology;Executive Function/physiology;Female;Humans;Image Processing, Computer-Assisted;Intercellular Signaling Peptides and Proteins/genetics;*Language;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Nerve Net/*pathology;Neuropsychological Tests;Parietal Lobe/pathology;Temporal Lobe/pathology;tau Proteins/genetics","Rohrer, J. D.;Ridgway, G. R.;Crutch, S. J.;Hailstone, J.;Goll, J. C.;Clarkson, M. J.;Mead, S.;Beck, J.;Mummery, C.;Ourselin, S.;Warrington, E. K.;Rossor, M. N.;Warren, J. D.",2010,Jan 1,10.1016/j.neuroimage.2009.08.002,0,
1659,Subjects harboring presenilin familial Alzheimer’s disease mutations exhibit diverse white matter biochemistry alterations,"Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD.",apolipoprotein;apolipoprotein E;gamma secretase;neurotrophic factor;nicastrin;presenilin;Alzheimer disease;article;brain hemorrhage;enzyme linked immunosorbent assay;gene;gene expression;gene mutation;gray matter;human;human tissue;long term potentiation;mild cognitive impairment;neurofibrillary tangle;nuclear magnetic resonance imaging;optical density;protein structure;PSEN1 gene;PSEN2 gene;Western blotting,"Roher, A. E.;Maarouf, C. L.;Malek-Ahmadi, M.;Wilson, J.;Kokjohn, T. A.;Daugs, I. D.;Whiteside, C. M.;Kalback, W. M.;Macias, M. P.;Jacobson, S. A.;Sabbagh, M. N.;Ghetti, B.;Beach, T. G.",2013,,,0,
1660,Neuropathology and amyloid-β spectrum in a bapineuzumab immunotherapy recipient,"The field of Alzheimer's disease (AD) research eagerly awaits the results of a large number of Phase III clinical trials that are underway to investigate the effectiveness of anti-amyloid-β (Aβ) immunotherapy for AD. In this case report, we review the pertinent clinical history, examine the neuropathology, and characterize the Aβ profile of an AD patient who received bapineuzumab immunotherapy. The patient received four bapineuzumab infusions over a 39 week period. During the course of this treatment, there was no remarkable change in cognitive impairment as determined by MMSE scores. Forty-eight days after the fourth bapineuzumab infusion was given, MRI revealed that the patient had developed lacunar infarcts and possible vasogenic edema, probably related to immunotherapy, but a subsequent MRI scan 38 days later demonstrated resolution of vasogenic edema. The patient expired due to acute congestive heart failure complicated by progressive AD and cerebrovascular accident 378 days after the first bapineuzumab infusion and 107 days after the end of therapy. Neuropathological and biochemical analysis did not produce evidence of lasting plaque regression or clearance of Aβ due to immunotherapy. The Aβ species profile of this case was compared with non-immunized AD cases and non-demented controls and found to be similar to non-immunized AD cases. SELDI-TOF mass spectrometric analysis revealed the presence of full-length Aβ1-42 and truncated Aβ peptides demonstrating species with and without bapineuzumab specific epitopes. These results suggest that, in this particular case, bapineuzumab immunotherapy neither resulted in detectable clearance of amyloid plaques nor prevented further cognitive impairment. © 2011 - IOS Press and the authors. All rights reserved.",amyloid beta protein;amyloid beta protein[1-42];apolipoprotein E;bapineuzumab;dexamethasone;donepezil;epitope;placebo;rivastigmine;tumor necrosis factor alpha;acute heart infarction;aged;Alzheimer disease;amyloid plaque;article;asthma;ataxia;basal ganglion;brain atherosclerosis;brain circulus arteriosus;brain edema;brain infarction;brain weight;case report;caudate nucleus;cause of death;cerebrospinal fluid analysis;cerebrovascular accident;chemical analysis;cognitive defect;computer assisted tomography;congestive heart failure;consciousness disorder;controlled study;coronary artery atherosclerosis;coronary stent;dementia;depigmentation;depression;drug clearance;drug substitution;drug withdrawal;electroencephalography;entorhinal cortex;epileptic discharge;family history;fast protein liquid chromatography;female;gait disorder;gastrointestinal reflux;gliosis;globus pallidus;high performance liquid chromatography;hippocampus;histopathology;human;human tissue;hypercholesterolemia;hypertension;immunoreactivity;immunotherapy;leptomeninx;leukocyte;male;mammillary body;medical history;Mini Mental State Examination;neurofibrillary tangle;neuropathology;nuclear magnetic resonance imaging;priority journal;protein blood level;Purkinje cell;putamen;substantia nigra;subthalamus;surface enhanced laser desorption ionization time of flight mass spectrometry;white matter;aricept;exelon,"Roher, A. E.;Maarouf, C. L.;Daugs, I. D.;Kokjohn, T. A.;Hunter, J. M.;Sabbagh, M. N.;Beach, T. G.",2011,,,0,
1661,Computerized history and self-assessment questionnaire for diagnostic screening among patients with dementia,"In order to standardize and quantify diagnostic information derived from medical histories and case reports given by demented patients, their families or care-providers, a questionnaire has been developed containing 94 questions. The output is categorized by computer into graphic clinical scales which correlate and weigh information relating to seven of the most common causes of dementia. The present investigation assesses the validity of predictive diagnostic classifications derived from the clinical scales tested on admission by correlating them later with final diagnoses determined independently by thorough clinical evaluation including standard diagnostic tests, computed tomography and nuclear magnetic resonance scans. Results of 101 healthy, neurologically normal, age-matched volunteers and 140 patients representative of the more common forms of dementia indicate that correct diagnostic identification was: 75% for dementia secondary to Parkinson's disease, 100% for Huntington's disease, 90.2% for Alzheimer's disease, 82.4% for multi-infarct dementia, 90.0% for posttraumatic dementia, 77.8% for normal-pressure hydrocephalus and 85.7% for Wernicke-Korsakoff dementia. Correct diagnostic assignment was highly significant (P less than .0005). The screening questionnaire may prove to be a useful and standard diagnostic tool for clinicians and investigators concerned with epidemiology, prevention and treatment of dementia.","Adult;Aged;Alzheimer Disease/complications;Dementia/*diagnosis/etiology;*Diagnosis, Computer-Assisted;Female;Humans;Huntington Disease/complications;Male;Middle Aged;Parkinson Disease/complications;Self-Assessment;Surveys and Questionnaires","Rogers, R. L.;Meyer, J. S.",1988,Jan,,0,
1662,Changes in parahippocampal white matter integrity in amnestic mild cognitive impairment: A diffusion tensor imaging study,"In the present study, changes in the parahippocampal white matter (PWM), in the region that includes the perforant path, were investigated, in vivo, in 14 individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2) diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and fractional anisotropy (FA); and (3) tractography were used. In addition, regression models were utilized to examine the association of PWM measurements with memory decline. The results from this study confirm previous findings in our laboratory and others, showing that compared to controls, individuals with aMCI have PWM volume loss. In addition to volume reduction, participants with aMCI demonstrated a significant increase in MD, but no difference in FA, both in the PWM region and in fibers modeled to pass through the PWM region. Further, the DTI metric of MD was associated with declarative memory performance, suggesting it may be a sensitive marker for memory dysfunction. These results indicate that there is general tissue loss and degradation (decreased volume; increased MD) in individuals with aMCI compared to older people with normal cognitive function. However, the microstructural organization of remaining fibers, as determined by measures of anisotropic diffusion, is not significantly different from that of controls. © 2009-IOS Press and the authors. All rights reserved.",,"Rogalski, E. J.;Murphy, C. M.;Detoledo-Morrell, L.;Shah, R. C.;Moseley, M. E.;Bammer, R.;Stebbins, G. T.",2009,2009,,0,
1663,Age-related changes in parahippocampal white matter integrity: a diffusion tensor imaging study,"The axons in the parahippocampal white matter (PWM) region that includes the perforant pathway relay multimodal sensory information, important for memory function, from the entorhinal cortex to the hippocampus. Previous work suggests that the integrity of the PWM shows changes in individuals with amnestic mild cognitive impairment and is further compromised as Alzheimer's disease progresses. The present study was undertaken to determine the effects of healthy aging on macro- and micro-structural alterations in the PWM. The study characterized in vivo white matter changes in the parahippocampal region that includes the perforant pathway in cognitively healthy young (YNG, n=21) compared to cognitively healthy older (OLD, n=21) individuals using volumetry, diffusion tensor imaging (DTI) and tractography. Results demonstrated a significant reduction in PWM volume in old participants, with further indications of reduced integrity of remaining white matter fibers. In logistic regressions, PWM volume, memory performance and DTI indices of PWM integrity were significant indicator variables for differentiating the young and old participants. Taken together, these findings suggest that age-related alterations do occur in the PWM region and may contribute to the normal decline in memory function seen in healthy aging by degrading information flow to the hippocampus.","Adult;Age Factors;Aged;Aged, 80 and over;Aging/ pathology;Diffusion Tensor Imaging;Female;Humans;Logistic Models;Male;Memory;Memory Disorders/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Organ Size;Perforant Pathway/ pathology;Temporal Lobe/ pathology","Rogalski, E.;Stebbins, G. T.;Barnes, C. A.;Murphy, C. M.;Stoub, T. R.;George, S.;Ferrari, C.;Shah, R. C.;deToledo-Morrell, L.",2012,Jul,10.1016/j.neuropsychologia.2012.03.033,0,
1664,Neuroanatomical correlates of verbal fluency in early Alzheimer's disease and normal aging,"Verbal fluency (VF) impairments occur early in Alzheimer's disease (AD) and to a lesser extent also in normal aging. However, the neural underpinnings of these impairments are not fully understood. The present study evaluated whether VF impairments in early AD and normal aging rely upon common or different neuroanatomical correlates. We examined the association between VF performance and brain structure in 18 mild AD patients and 24 healthy elderly. Linear regressions were performed between accuracy and time intervals in VF scores and structural measurements of cerebral gray matter (GM) and white matter (WM) using MRI. Results showed that semantic VF correlated exclusively with GM in cerebellum, left temporal fusiform cortex, and WM in uncinate fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Phonemic VF showed unique associations between intervals and WM in left-hemisphere tracts. The association between GM in hippocampus, subcortical structures and semantic accuracy differentiated patients from controls. Results showed that VF impairments are primarily associated with same structural brain changes in AD as in healthy elderly but at exaggerated levels. However, specific VF deficiencies and their underlying neural correlates exist and these clearly differentiate the initial stages of AD.",Dti;Gray matter loss;Mild Alzheimer's disease;Normal aging;Vbm;Verbal fluency;White matter degeneration;Word retrieval,"Rodriguez-Aranda, C.;Waterloo, K.;Johnsen, S. H.;Eldevik, P.;Sparr, S.;Wikran, G. C.;Herder, M.;Vangberg, T. R.",2016,Apr 7,10.1016/j.bandl.2016.03.001,0,
1665,proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke,"Background: Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis. Objective: The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke. Methods: We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-α (TNFα), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP-10 was assessed in vitro. Results: Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05). Conclusions: Increased serum proMMP-10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome. © 2013 International Society on Thrombosis and Haemostasis.",fibronectin;interleukin 6;messenger RNA;stromelysin 2;tissue inhibitor of metalloproteinase 1;tumor necrosis factor alpha;adult;aged;article;asymptomatic disease;brain damage;brain edema;brain ischemia;brain size;clinical assessment;comparative study;controlled study;disease severity;enzyme blood level;female;genetic association;high resolution computer tomography;hospital admission;human;human cell;in vitro study;major clinical study;male;mental deterioration;mental function;National Institutes of Health Stroke Scale;outcome assessment;priority journal;prospective study;protein blood level;Rankin scale,"Rodríguez, J. A.;Sobrino, T.;Orbe, J.;Purroy, A.;Martínez-Vila, E.;Castillo, J.;Páramo, J. A.",2013,,,0,
1666,Association of annular calcification and aortic valve sclerosis with brain findings on magnetic resonance imaging in community dwelling older adults: The cardiovascular health study,"Objectives: The objective of this study was to investigate the associations of mitral annular calcification, aortic annular calcification, and aortic valve sclerosis with covert magnetic resonance imaging (MRI)defined brain infarcts. Background: Clinically silent brain infarcts defined by MRI are associated with increased risk for cognitive decline, dementia, and future overt stroke. Left-sided cardiac valvular and annular calcifications are suspected as risk factors for clinical ischemic stroke. Methods: A total of 2,680 CHS (Cardiovascular Health Study) participants without clinical histories of stroke or transient ischemic attack underwent brain MRI in 1992 and 1993, 1 to 2 years before echocardiographic exams (1994 to 1995). Results: The mean age of the participants was 74.5 ± 4.8 years, and 39.3% were men. The presence of any annular or valvular calcification (mitral annular calcification, aortic annular calcification, or aortic valve sclerosis), mitral annular calcification alone, or aortic annular calcification alone was significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular or valve calcification remained associated with covert brain infarcts (risk ratio: 1.24; 95% confidence interval: 1.05 to 1.47). The degree of annular or valvular calcification severity showed a direct relation with the presence of covert MRI findings. Conclusions: Left-sided cardiac annular and valvular calcifications are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening in the progression of annular and valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk for cognitive impairment and future stroke. © 2011 American College of Cardiology Foundation.",,"Rodriguez, C. J.;Bartz, T. M.;Longstreth Jr, W. T.;Kizer, J. R.;Barasch, E.;Lloyd-Jones, D. M.;Gottdiener, J. S.",2011,24,,0,
1667,Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors,"Background. A specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors. Methods. In a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age <21 years and 16 patients who did not receive CRT, we determined the presence of CMBs on brain MRIs. Neurocognitive function was assessed using a computerized testing program (CogState). We used survival analysis to determine cumulative incidence of CMBs and Poisson regression to examine risk factors for CMBs. Linear regression models were used to assess effect of CMBs on neurocognitive function. Results. The cumulative incidence of CMBs was 48.8% (95% CI: 38.3-60.5) at 5 years. Children who had whole brain irradiation developed CMBs at a rate 4 times greater than those treated with focal irradiation (P <. 001). In multivariable analysis, children with CMBs performed worse on the Groton Maze Learning test (GML) compared with those without CMBs (Z-score-1.9; 95% CI:-2.7,-1.1; P <. 001), indicating worse executive function when CMBs are present. CMBs in the frontal lobe were associated with worse performance on the GML (Z-score-2.4; 95% CI:-2.9,-1.8; P <. 001). Presence of CMBs in the temporal lobes affected verbal memory (Z-score-2.0; 95% CI:-3.3,-0.7; P =. 005). Conclusion. CMBs are common and associated with neurocognitive dysfunction in pediatric brain tumor survivors treated with radiation.",bevacizumab;adult;article;brain hemorrhage;brain radiation;brain radiography;brain tumor;cancer incidence;cancer radiotherapy;cancer survival;cognition;cognitive defect;cohort analysis;diffusion weighted imaging;disease association;dosimetry;executive function;female;frontal lobe;human;incidence;major clinical study;male;nuclear magnetic resonance imaging;pediatrics;radiation dose;risk factor;verbal memory;working memory;young adult,"Roddy, E.;Sear, K.;Felton, E.;Tamrazi, B.;Gauvain, K.;Torkildson, J.;Buono, B. D.;Samuel, D.;Haas-Kogan, D. A.;Chen, J.;Goldsby, R. E.;Banerjee, A.;Lupo, J. M.;Molinaro, A. M.;Fullerton, H. J.;Mueller, S.",2016,,10.1093/neuonc/now163,0,
1668,Recent imaging advances in neurology,"Over the recent years, the application of neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) has considerably advanced the understanding of complex neurological disorders. PET is a powerful molecular imaging tool, which investigates the distribution and binding of radiochemicals attached to biologically relevant molecules; as such, this technique is able to give information on biochemistry and metabolism of the brain in health and disease. MRI uses high intensity magnetic fields and radiofrequency pulses to provide structural and functional information on tissues and organs in intact or diseased individuals, including the evaluation of white matter integrity, grey matter thickness and brain perfusion. The aim of this article is to review the most recent advances in neuroimaging research in common neurological disorders such as movement disorders, dementia, epilepsy, traumatic brain injury and multiple sclerosis, and to evaluate their contribution in the diagnosis and management of patients.",,"Rocchi, L.;Niccolini, F.;Politis, M.",2015,Sep,10.1007/s00415-015-7711-x,0,
1669,A magnetic resonance imaging study of the cervical cord of patients with CADASIL,"The authors obtained MR and magnetization transfer (MT) imaging of the cervical cord from 25 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). They found no conventional MR abnormalities, but a reduced peak height of the MT ratio (MTR) histogram. This suggests a reduced amount of ""truly"" normal cord tissue in CADASIL. A significant correlation was found between the extent of brain lesions and cord MTR, suggesting wallerian degeneration as the substrate of the cord MTR changes.","Adult;Age Factors;Brain/pathology/physiopathology;Cervical Vertebrae;Dementia, Multi-Infarct/ pathology/physiopathology;Disability Evaluation;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Spinal Cord/ pathology/physiopathology","Rocca, M. A.;Filippi, M.;Herzog, J.;Sormani, M. P.;Dichgans, M.;Yousry, T. A.",2001,May 22,,0,
1670,Common neuropathological features underlie distinct clinical presentations in three siblings with hereditary diffuse leukoencephalopathy with spheroids caused by CSF1R p.Arg782His,"Hereditary diffuse leukoencephalopathy with spheroids (HDLS) presents with a variety of clinical phenotypes including motor impairments such as gait dysfunction, rigidity, tremor and bradykinesia as well as cognitive deficits including personality changes and dementia. In recent years, colony stimulating factor 1 receptor gene (CSF1R) has been identified as the primary genetic cause of HDLS. We describe the clinical and neuropathological features in three siblings with HDLS and the CSF1R p.Arg782His (c.2345G > A) pathogenic mutation. Each case had varied motor symptoms and clinical features, but all included slowed movements, poor balance, memory impairment and frontal deficits. Neuroimaging with magnetic resonance imaging revealed atrophy and increased signal in the deep white matter. Abundant white matter spheroids and CD68-positive macrophages were the predominant pathologies in these cases. Similar to other cases reported in the literature, the three cases described here had varied clinical phenotypes with a pronounced, but heterogeneous distribution of axonal spheroids and distinct microglia morphology. Our findings underscore the critical importance of genetic testing for establishing a clinical and pathological diagnosis of HDLS.",arginine;colony stimulating factor 1;histidine;case report;female;genetics;human;leukoencephalopathy;male;middle aged;mutation;pathology;sibling,"Robinson, J. L.;Suh, E.;Wood, E. M.;Lee, E. B.;Coslett, H. B.;Raible, K.;Lee, V. M. Y.;Trojanowski, J. Q.;Van Deerlin, V. M.",2015,,10.1186/s40478-015-0219-x,0,
1671,Progressive lupus dementia. 2 cases with or without antiphospholipid antibodies,Two cases of lupus dementia presented many points of particular interest :1) the progressive installation of intellectual deterioration inaugural for the first observation; 2) the diagnostic difficulties of neurolupus with the ARA criteria; 3) the appearance of cerebral magnetic resonance imaging with confluent hypersignals of the periventricular white matter on T2-weighted images; 4) the pathophysiological hypotheses: vascular disease ? immunologic disease ?; 5) the clinical improvement and SPECT amelioration for the second patient with corticosteroids.,,"Robin, C.;Gonnaud, P. M.;Durieu, I.;Croisile, B.;Garassus, P.;Levrat, R.;Chazot, G.;Aimard, G.;Trillet, M.",1995,1995,,0,
1672,"Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders","BACKGROUND: Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. METHODS: In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. RESULTS: Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size >/= 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). CONCLUSIONS: These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders.",Cerebral blood flow;Orthostatic hypotension;Parkinson's disease;Supine hypertension;Visuospatial,"Robertson, A. D.;Messner, M. A.;Shirzadi, Z.;Kleiner-Fisman, G.;Lee, J.;Hopyan, J.;Lang, A. E.;Black, S. E.;MacIntosh, B. J.;Masellis, M.",2016,Jan,10.1016/j.parkreldis.2015.11.019,0,
1673,Association of type 2 diabetes with brain atrophy and cognitive impairment,"OBJECTIVE: We investigated the associations of diabetes and hypertension with imaging biomarkers (markers of neuronal injury and ischemic damage) and with cognition in a population-based cohort without dementia. METHODS: Participants (n = 1,437, median age 80 years) were evaluated by a nurse and physician and underwent neuropsychological testing. A diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia was made by an expert panel. Participants underwent MRI to determine cortical and subcortical infarctions, white matter hyperintensity (WMH) volume, hippocampal volume (HV), and whole brain volume (WBV). The medical records were reviewed for diabetes and hypertension in midlife or later. RESULTS: Midlife diabetes was associated with subcortical infarctions (odds ratio, 1.85 [95% confidence interval, 1.09-3.15]; p = 0.02), reduced HV (-4% [-7 to -1.0]; p = 0.01), reduced WBV (-2.9% [-4.1 to -1.6]), and prevalent MCI (odds ratio, 2.08; p = 0.01). The association between diabetes and MCI persisted with adjustment for infarctions and WMH volume but was attenuated after adjustment for WBV (1.60 [0.87-2.95]; p = 0.13) and HV (1.82 [1.00-3.32]; p = 0.05). Midlife hypertension was associated with infarctions and WMH volume and was marginally associated with reduced performance in executive function. Effects of late-life onset of diabetes and hypertension were few. CONCLUSIONS: Midlife onset of diabetes may affect late-life cognition through loss of brain volume. Midlife hypertension may affect executive function through ischemic pathology. Late-life onset of these conditions had fewer effects on brain pathology and cognition.","Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Cognition Disorders/ diagnosis/ epidemiology;Cohort Studies;Diabetes Mellitus, Type 2/ diagnosis/ epidemiology;Female;Humans;Hypertension/diagnosis/epidemiology;Male;Population Surveillance/ methods;Prospective Studies;Risk Factors","Roberts, R. O.;Knopman, D. S.;Przybelski, S. A.;Mielke, M. M.;Kantarci, K.;Preboske, G. M.;Senjem, M. L.;Pankratz, V. S.;Geda, Y. E.;Boeve, B. F.;Ivnik, R. J.;Rocca, W. A.;Petersen, R. C.;Jack, C. R., Jr.",2014,Apr 1,10.1212/wnl.0000000000000269,0,
1674,Electroencephalography and computerised tomography in vascular and non-vascular dementia in old age,"Nine normal elderly subjects and 81 patients with dementia have been studied by computerised tomography (CT) and electroencephalography (EEG). There was a broad relationship between slowing of the basic frequency of the EEG and the severity of mental impairment. Localised slow-wave activity was found in 19% of those with non-vascular dementia and 72% of those with dementia of vascular origin. The mean size of the ventricles, as determined from CT scans, was larger in the vascular than in the non-vascular group. Within the vascular group it was larger in those without than in those with visible infarcts. There was no relationship in either group between ventricular size and dominant EEG frequency.","Aged;Brain/*physiopathology;Cerebral Ventricles/anatomy & histology;Cerebrovascular Disorders/complications/diagnosis/*physiopathology;Dementia/etiology/*physiopathology;*Electroencephalography;Female;Humans;Male;Middle Aged;Psychological Tests;*Tomography, X-Ray Computed","Roberts, M. A.;McGeorge, A. P.;Caird, F. I.",1978,Oct,,0,
1675,Extensive intracranial microbleeds in transthyretin amyloidosis,,anticoagulant agent;antithrombocytic agent;baclofen;etiracetam;fosphenytoin sodium;metoprolol;nicardipine;phenytoin;prealbumin;aged;amyloidosis;anamnesis;blood pressure regulation;CADASIL;case report;clinical examination;clinical feature;computer assisted tomography;cranial nerve;echography;electroencephalography;emergency ward;female;femoral vein;hospital discharge;human;hypertension;intensive care unit;international normalized ratio;letter;magnetic resonance angiography;mental health;nuclear magnetic resonance imaging;serology;subarachnoid hemorrhage;subiculum;tendon reflex;thrombocyte count;tonic clonic seizure;transthoracic echocardiography;vein thrombosis,"Robbins, M. S.;Yasen, J.",2008,,,0,
1676,Evaluating imaging biomarkers for neurodegeneration in pre-symptomatic Huntington's disease using machine learning techniques,"The development of MRI measures as biomarkers for neurodegenerative disease could prove extremely valuable for the assessment of neuroprotective therapies. Much current research is aimed at developing such biomarkers for use in people who are gene-positive for Huntington's disease yet exhibit few or no clinical symptoms of the disease (pre-HD). We acquired structural (T1), diffusion weighted and functional MRI (fMRI) data from 39 pre-HD volunteers and 25 age-matched controls. To determine whether it was possible to decode information about disease state from neuroimaging data, we applied multivariate pattern analysis techniques to several derived voxel-based and segmented region-based datasets. We found that different measures of structural, diffusion weighted, and functional MRI could successfully classify pre-HD and controls using support vector machines (SVM) and linear discriminant analysis (LDA) with up to 76% accuracy. The model producing the highest classification accuracy used LDA with a set of six volume measures from the basal ganglia. Furthermore, using support vector regression (SVR) and linear regression models, we were able to generate quantitative measures of disease progression that were significantly correlated with established measures of disease progression (estimated years to clinical onset, derived from age and genetic information) from several different neuroimaging measures. The best performing regression models used SVR with neuroimaging data from regions within the grey matter (caudate), white matter (corticospinal tract), and fMRI (insular cortex). These results highlight the utility of machine learning analyses in addition to conventional ones. We have shown that several neuroimaging measures contain multivariate patterns of information that are useful for the development of disease-state biomarkers for HD.","Adult;Algorithms;Artificial Intelligence;Asymptomatic Diseases;Brain/pathology;Brain Mapping/ methods;Computer Simulation;Disease Progression;Female;Humans;Huntington Disease/ pathology;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/pathology;Young Adult","Rizk-Jackson, A.;Stoffers, D.;Sheldon, S.;Kuperman, J.;Dale, A.;Goldstein, J.;Corey-Bloom, J.;Poldrack, R. A.;Aron, A. R.",2011,May 15,10.1016/j.neuroimage.2010.04.273,0,
1677,Neuropsychological testing may predict early progression of asymptomatic adrenoleukodystrophy,"OBJECTIVES: To investigate the correlation between neuropsychological and MRI findings in children with the childhood cerebral (CCALD) and asymptomatic forms of X-linked adrenoleukodystrophy (ALD) and to identify early cognitive markers that may predict disease progression in asymptomatic children with ALD. BACKGROUND: The few published neuropsychological studies on CCALD suggest a correlation between the pattern of cognitive deficit and lesion site; however, neuropsychological performance in asymptomatic children with ALD has not been investigated. METHODS: The authors assessed cognitive function and cerebral MRI findings in seven CCALD and eight asymptomatic ALD children. RESULTS: The CCALD children's cognitive skills were severely compromised, especially Wechsler and executive functions. Visual perception, short-term memory, and language were generally preserved, except that naming was severely impaired. All had extensive posterior white matter deterioration. The asymptomatic children had relatively intact neuropsychological performance, but their verbal fluency was compromised and naming severely impaired. All except one had mild white matter alterations. For all the children, the majority of neuropsychological test performance correlated significantly with extent of white matter lesions. CONCLUSIONS: The pattern of cognitive deterioration in children with CCALD and the significant correlation of neuropsychological test performance with extent of white matter lesions indicate a white matter dementia similar to that observed in adults with demyelinating diseases. The deficits found in asymptomatic children, despite their normal intelligence, suggest that careful neuropsychological investigation can identify early signs of malfunction. These may be markers of disease progression useful for selecting children for bone marrow transplant, although this will require confirmation by prospective longitudinal studies.","Adolescent;Adrenoleukodystrophy/*diagnosis/diet therapy;Brain/pathology;Child;Child, Preschool;Cognition Disorders/*diagnosis;Disease Progression;Humans;Magnetic Resonance Imaging;Male;*Neuropsychological Tests;Predictive Value of Tests;Speech Disorders/diagnosis","Riva, D.;Bova, S. M.;Bruzzone, M. G.",2000,Apr 25,,0,
1678,Brain volumetric changes and cognitive ageing during the eighth decade of life,"Later-life changes in brain tissue volumes-decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)-are strong candidates to explain some of the variation in ageing-related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow-age sample of older individuals (n=657 with brain volumetric data at the initial wave, n=465 at follow-up). We used latent variable modeling to extract error-free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r-values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life. Hum Brain Mapp 36:4910-4925, 2015.",aged;article;brain size;cognition;cognitive aging;female;human;intelligence;life;male;memory;mental deterioration;neuroimaging;nuclear magnetic resonance imaging;priority journal;volumetry;white matter,"Ritchie, S. J.;Dickie, D. A.;Cox, S. R.;Valdes Hernandez, M. D. C.;Corley, J.;Royle, N. A.;Pattie, A.;Aribisala, B. S.;Redmond, P.;Muñoz Maniega, S.;Taylor, A. M.;Sibbett, R.;Gow, A. J.;Starr, J. M.;Bastin, M. E.;Wardlaw, J. M.;Deary, I. J.",2015,,,0,
1679,Coupled changes in brain white matter microstructure and fluid intelligence in later life,"Understanding aging-related cognitive decline is of growing importance in aging societies, but relatively little is known about its neural substrates. Measures of white matter microstructure are known to correlate cross-sectionally with cognitive ability measures, but only a few small studies have tested for longitudinal relations among these variables. We tested whether there were coupled changes in brain white matter microstructure indexed by fractional anisotropy (FA) and three broad cognitive domains (fluid intelligence, processing speed, and memory) in a large cohort of human participants with longitudinal diffusion tensor MRI and detailed cognitive data taken at ages 73 years (n = 731) and 76 years (n = 488). Longitudinal changes in white matter microstructure were coupled with changes in fluid intelligence, but not with processing speed or memory. Individuals with higher baseline white matter FA showed less subsequent decline in processing speed. Our results provide evidence for a longitudinal link between changes in white matter microstructure and agingrelated cognitive decline during the eighth decade of life. They are consistent with theoretical perspectives positing that a corticocortical “disconnection” partly explains cognitive aging.",aged;aging;arcuate nucleus;article;cingulum (brain);cognition;corpus callosum;diffusion tensor imaging;female;fluid intelligence;fractional anisotropy;human;inferior longitudinal fasciculus;latent period;male;memory;priority journal;processing speed;response time;thalamus anterior nucleus;tractography;uncinate fasciculus;white matter;white matter microstructure,"Ritchie, S. J.;Bastin, M. E.;Tucker-Drob, E. M.;Maniega, S. M.;Engelhardt, L. E.;Cox, S. R.;Royle, N. A.;Gow, A. J.;Corley, J.;Pattie, A.;Taylor, A. M.;Valdés Hernández, M. C.;Starr, J. M.;Wardlaw, J. M.;Deary, I. J.",2015,,,0,
1680,Retrospective identification and characterization of mild cognitive impairment from a prospective population cohort,"OBJECTIVES: Mild cognitive impairment (MCI) case-finding criteria have low specificity in general population studies. This study retrospectively identifies cases of MCI and determines baseline criteria giving the highest discriminability. The ability of these criteria to increase current case detection specificity is estimated. DESIGN: A population-based cohort was recruited from electoral rolls from three French cities. Clinical and environmental characteristics were evaluated at baseline and at 2- and 4-year follow-up. The clinical characteristics of incident cases of dementia were examined retrospectively. PARTICIPANTS: Eight thousand nine hundred nineteen persons aged 65 years and older without dementia (60.8% women) were included in this study. The mean age (SD) of the participants was 74.2 (5.6) years for men and 74.4 (5.6) years for women. RESULTS: Three hundred twenty persons (3.6%) were retrospectively classified as MCI at baseline. This MCI group had poorer performance on all cognitive tests compared with the rest of the cohort, and a subsample undergoing MRI were found to have more white matter hyperintensities. The group were also characterized by the presence of an ApoE epsilon4 genotype (odds ratio [OR]: 2.17, confidence interval [CI]: 1.44-3.29 for men; OR: 2.27, CI: 1.59-3.24 for women) and instrumental activities of daily living loss (OR: 1.72, CI: 1.01-3.0 for men; OR: 1.49; CI: 0.97-2.3 for women). Women with MCI also had high depressive symptomatology (OR: 1.96; CI: 1.34-2.87), anticholinergic drug use (OR: 1.59; CI: 1.05-2.28), and low body mass index (OR: 1.54, CI: 1.05-2.28) and for men a history of stroke (OR: 2.17, CI: 1.16-4.05) and glycemia (OR: 1.72, CI: 1.13-2.71). Addition of these characteristics to conventional MCI definitions increases their specificity. CONCLUSIONS: This general population study using a retrospective method for classifying persons with MCI identified gender-specific noncognitive clinical variables that may increase specificity.","Activities of Daily Living;Aged;Apolipoprotein E4/genetics;Cognition Disorders/*diagnosis;Dementia/diagnosis;Disease Progression;Female;Genotype;Geriatric Assessment/*methods;Humans;Male;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Retrospective Studies;Risk Factors","Ritchie, K.;Ancelin, M. L.;Beaino, E.;Portet, F.;Brickman, A. M.;Dartigues, J. F.;Tzourio, C.;Dupuy, A. M.;Ritchie, C. W.;Berr, C.;Artero, S.",2010,Aug,,0,
1681,The PREVENT study: A prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer's disease,"Introduction: Epidemiological studies indicate that significant decreases in the incidence of Alzheimer's disease (AD) may be obtained by targeting multiple middle-age risk factors. However, as dementia is unlikely to be diagnosed for decades, short-term outcome measures are required. AD biomarker changes precede clinical symptoms by many years, but their sensitivity to mid-life change remains unknown. Methods and analysis: PREVENT is a prospective cohort study examining biomarker status at mid-life in at least 150 individuals genetically at high, medium or low risk of late-onset AD. Participants are children of individuals with or without a diagnosed AD allocated to high, medium and low-risk groups according to parental clinical status and ApoE genotype. The biomarkers examined over 2 years are plasma and CSF Aβ42 amyloid, Tau and pTau, proinflammatory cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter lesion volume, cognitive performance related to transentorhinal and hippocampal functioning and hypothalamic-pituitary-adrenal and sympathetic axes regulation. Ethics and dissemination: Detected pathologies are communicated to the participant ' s general practitioner with their permission. Risk status by genotype would not be revealed. The results of the study would be published in peer-reviewed journals and validated biomarkers used to construct a randomised controlled intervention study.",amyloid beta protein[1-42];biological marker;C reactive protein;gamma interferon;haptoglobin;interleukin 18;interleukin 1alpha;interleukin 1beta;interleukin 6;interleukin 8;orosomucoid;phosphoprotein;sialic acid;tau protein;tumor necrosis factor alpha;adrenergic system;adult;Alzheimer disease;article;brain atrophy;brain size;cognition;cohort analysis;diffusion weighted imaging;entorhinal cortex;genetic risk;genotype;high risk patient;hippocampus;human;hypothalamus hypophysis adrenal system;inflammation;information dissemination;middle aged;neuroimaging;nuclear magnetic resonance imaging;onset age;peer review;prospective study;protein blood level;protein cerebrospinal fluid level;research ethics;temporal lobe;white matter lesion,"Ritchie, C. W.;Ritchie, K.",2012,,,0,
1682,Cerebral hemorrhages in CADASIL: report of four cases and a brief review,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. However, cerebral microbleeds have been found in 31-69% of CADASIL patients. METHODS: We describe four unrelated CADASIL patients who had hemorrhagic strokes. We also briefly review the literature on intracerebral hemorrhage (ICH) in CADASIL. RESULTS: Three patients had a thalamo-capsular hemorrhage (age at onset: 54, 67, 77) and one of these had a second hemispheric cerebellar hemorrhage. Another patient experienced an interpeduncular cistern subarachnoid hemorrhage when he was 39. None of these patients was receiving antiplatelets, anticoagulants or statins at the time of hemorrhage; all were hypertensive. NOTCH3 gene analysis revealed mutations on exons 14, 22 (two patients presenting the same mutation), and 24. MRI signs of previous hemorrhages were present in all these patients. CONCLUSIONS: Hemorrhagic stroke can occur in CADASIL similarly to sporadic cerebral small vessel diseases; this finding expands the phenotype of the disease. A diagnosis of CADASIL should probably be considered also in patients with ICH. These data bear potential implications in terms of need of better control of risk factors, particularly hypertension, and raise relevant questions about the use of antiplatelets as prevention measures in CADASIL patients.","Adult;Aged;CADASIL/*complications/genetics;Female;Hemiplegia/etiology;Humans;Internal Capsule/pathology;Intracranial Hemorrhages/*etiology/genetics;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/genetics/physiology;Receptors, Notch/genetics;Stroke/etiology;Subarachnoid Hemorrhage/etiology;Thalamus/pathology;Tomography, X-Ray Computed","Rinnoci, V.;Nannucci, S.;Valenti, R.;Donnini, I.;Bianchi, S.;Pescini, F.;Dotti, M. T.;Federico, A.;Inzitari, D.;Pantoni, L.",2013,Jul 15,10.1016/j.jns.2013.04.002,0,
1683,Clinical thinking and decision-making in practice. A conductor with epilepsy followed by memory defects,"A 40-year-old conductor was admitted because of increasing drowsiness and confusion. Two years before admission he had a first seizure. One year before admission he had a generalized convulsive status epilepticus, the following months he was less able to concentrate. A second status epilepticus was followed by transient weakness of his left arm and a depressed level of consciousness for several weeks. After awakening, he had delusions, and his wife found him demented. In the following months his confusion and drowsiness gradually deteriorated. He had previously had gonorrhoea, an episode of fever and exanthema, and was found to have oligospermia as cause of his infertility. On examination he was disoriented, and he had dysarthria. His left pupil was smaller, but both pupils reacted normally. There was left hemianopia and cerebellar ataxia. CT and MR showed large ventricles and periventricular diffuse lesions in the white matter. CSF examination revealed leucocytosis and increased protein content. Further examination were focussed on serological evidence of syphilis, and finally neurosyphilis was diagnosed. After treatment with penicillin, the patient started to recover.",penicillin G;adult;case report;computer assisted tomography;epilepsy;human;male;medical decision making;nuclear magnetic resonance imaging;short survey;syphilis,"Rinkel, G. J. E.;Brouwers, P. J. A. M.;Lambrechts, D. A. J. E.",1997,,,0,
1684,Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations,"Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation. Persons destined to develop the disease by virtue of fully penetrant genetic alterations (familial Alzheimer's disease or FAD) provide a model in which early and even presymptomatic changes of the disease may be identified. In this study we performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk for inheriting an FAD mutation. We compared global and localized fractional anisotropy (FA) measures in white matter between FAD mutation carriers and non-carriers in the preclinical (clinical dementia rating <1, n = 20) and presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease. There were no significant differences between mutation carriers and non-carriers with regard to absolute age, age relative to the typical age of disease diagnosis in their family, gender or Mini-Mental Status Examination Score. Among preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P = 0.045), FA of the columns of the fornix (P = 0.012), area of the perforant pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n = 8). We also found that FA in the columns of the fornix (P = 0.008) and left orbitofrontal lobe white matter (P = 0.045) were decreased in the eight presymptomatic mutation carriers compared to seven non-carriers. Logistic regression demonstrated that FA of the columns of the fornix was a better predictor of mutation status than was cross-sectional area of the fornix, global mean white-matter FA and left frontal lobe white-matter FA. In a linear regression analysis, white-matter volume (P = 0.002), hippocampal volume (P = 0.023) and mutation status (P = 0.032) significantly predicted fornix FA. We conclude that FA is decreased in the white matter in preclinical and even presymptomatic FAD mutation carriers, particularly in the late-myelinating tracts connecting limbic structures. Decreased FA in of the columns of the fornix is particularly robust in early FAD and may provide a biomarker for early disease in sporadic Alzheimer's disease.","Adult;Age Factors;Alzheimer Disease/genetics/ pathology/psychology;Anisotropy;Brain/ pathology;Brain Mapping/methods;Diffusion Magnetic Resonance Imaging/methods;Female;Fornix, Brain/pathology;Heterozygote;Humans;Image Processing, Computer-Assisted/methods;Male;Mutation;Neuropsychological Tests;Psychiatric Status Rating Scales","Ringman, J. M.;O'Neill, J.;Geschwind, D.;Medina, L.;Apostolova, L. G.;Rodriguez, Y.;Schaffer, B.;Varpetian, A.;Tseng, B.;Ortiz, F.;Fitten, J.;Cummings, J. L.;Bartzokis, G.",2007,Jul,10.1093/brain/awm102,0,
1685,Hereditary and non-hereditary microangiopathies in the young. An up-date,"In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. © 2010 Elsevier B.V. All rights reserved.",,"Ringelstein, E. B.;Kleffner, I.;Dittrich, R.;Kuhlenbäumer, G.;Ritter, M. A.",2010,15,,0,
1686,Panencephalopathic type of Creutzfeldt-Jakob disease and special reference to its pyramydal tract degeneration,"An autopsy case of panencephalopathic type of Creutzfeldt-Jakob disease (P-CJD) was reported. The pyramidal tract degeneration in this case was analysed microscopically and compared with the secondary one caused by other disorders such as cerebral vascular diseases and spinal mass lesions. The patient, a 61 year old woman, was admitted on July 27, 1979 to our hospital because of rapidly progressive mental changes, which had begun on July 2. The neurological examination was almost normal except for psychic symptoms. Routine laboratory examinations including CT were normal. But the electroencephalogram demonstrated periodic lateralized epileptiform discharge in the left hemisphere. Within one month of hospitalization she became bedridden and decorticated. Positive Babinski's sign, generalized rigidity and myoclonus were also noted. About two months after admission she developed in the state of akinetic mutism, which lasted to her terminal. She died on November 2, 1980. Post mortem findings: The brain weighed 790 g, showing diffuse cerebro-cerebellar atrophy. Serial coronal section of the cerebral hemispheres disclosed a marked narrowing of the cerebral white matter with the enlarged lateral ventricles. The basal ganglia were atrophied and brownish in color. Microscopically, the cerebral cortical changes were extensive and destructive but for hippocumps. Almost total neuronal loss with marked proliferation of hypertrophic astrocytes were noted. Similar changes were also seen in the basal ganglia. The cerebral white matter showed diffuse destruction of myelin sheaths and axons with severe astrocytosis, and proliferation of many fat granule cells. The cerebellar degeneration consisted of pronounced loss of the granule cells and relative preservation of Purkinje cells with fibrillary gliosis. The substantia nigra, pontine nuclei and inferior olives were also affected. Corticospinal tracts in the cerebral peduncles, pontine base, pyramid and spinal cord were degenerated bilaterally. The pathological findings of these regions were very similar to that of the secondary degeneration caused by some cases of cerebral infarction. There was no obvious evidence to conclude the pyramidal tract degeneration in the brain stem and the spinal cord to be primary.",adult;autopsy;brain disease;case report;central nervous system;Creutzfeldt Jakob disease;diagnosis;electroencephalography;human;pyramidal tract,"Riku, S.;Okamoto, T.;Hashizume, Y.",1983,,,0,
1687,Dementia of adult polyglucosan body disease: Evidence of cortical and subcortical dysfunction,Objectives: To characterize the dementia associated with adult polyglucosan body disease (APBD) and to correlate the cognitive deficits with abnormalities found on magnetic resonance imaging (MRI). Methods: Quantitative neuropsychological testing and MRI in one man with APBD and a review of the literature. Results: The dementia of APBD affects cortical and subcortical functions. The cognitive deficits correlate with MRI findings of cortical atrophy and white-matter abnormalities. Conclusion: Neuropsychological testing and MRI are helpful in the evaluation of patients with APBD.,,"Rifai, Z.;Klitzke, M.;Tawil, R.;Kazee, A. M.;Shanske, S.;DiMauro, S.;Griggs, R. C.",1994,1994,,0,
1688,Differentiation of multi-infarct and Alzheimer dementia by intracranial hemodynamic parameters,"BACKGROUND AND PURPOSE: The differentiation between the Alzheimer and multi-infarct types of dementia may still be equivocal considering clinical criteria, neuropsychological tests, and imaging techniques. Cerebral microangiopathic alterations underlying multi-infarct dementia should allow the characterization of dementia subgroups. METHODS: Patients with a diagnosis of multi-infarct dementia (n = 17; mean age, 69.1 +/- 8.5 years) or Alzheimer dementia (n = 24, mean age, 65.8 +/- 9.0 years) according to standard testing criteria, clinical findings, and neuroimaging techniques (computed tomography and magnetic resonance imaging) were investigated prospectively by transcranial Doppler sonography and compared with a normal reference group (n = 64; mean age, 61.0 +/- 11.1 years). Transcranial Doppler sonography allows an indirect evaluation of peripheral flow resistance in the microcirculatory bed by quantifying pulsatility characteristics, as reflected in the effective pulsatility range (time-averaged mean blood flow velocity minus the peak-systolic to end-diastolic amplitude, in centimeters per second). RESULTS: A total of 204 vessels were investigated in 105 subjects. Mean and diastolic blood flow velocities as well as the effective pulsatility range were significantly lower in the multi-infarct dementia group compared with the Alzheimer and the normal reference groups (p < 0.001). By using receiver operating characteristic analysis, a cutoff point for effective pulsatility range values of -5 cm/sec gives a side-dependent sensitivity of 90.48-95.24% and a specificity of 64.71-70.59% in diagnosing Alzheimer-type dementia; the corresponding sensitivity and specificity for a value of -2 cm/sec are 82.35-88.24% and 80.95-90.48%, respectively. CONCLUSIONS: Pulsatility changes as reflected by the effective pulsatility range are a noninvasive additional criterion in the differential diagnosis of dementia.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/physiopathology/ultrasonography;Blood Flow Velocity;Dementia, Multi-Infarct/ diagnosis/physiopathology/ultrasonography;Diagnosis, Differential;Diastole/physiology;Female;Humans;Male;Middle Aged;Prospective Studies;Pulsatile Flow/ physiology;Sensitivity and Specificity;Systole/physiology","Ries, F.;Horn, R.;Hillekamp, J.;Honisch, C.;Konig, M.;Solymosi, L.",1993,Feb,,0,
1689,Sodium ((23)Na) ultra-short echo time imaging in the human brain using a 3D-Cones trajectory,"OBJECT: Sodium magnetic resonance imaging ((23)Na-MRI) of the brain has shown changes in (23)Na signal as a hallmark of various neurological diseases such as stroke, Alzheimer's disease, Multiple Sclerosis and Huntington's disease. To improve scan times and image quality, we have implemented the 3D-Cones (CN) sequence for in vivo (23)Na brain MRI. MATERIALS AND METHODS: Using signal-to-noise (SNR) as a measurement of sequence performance, CN is compared against more established 3D-radial k-space sampling schemes featuring cylindrical stack-of-stars (SOS) and 3D-spokes kooshball (KB) trajectories, on five healthy volunteers in a clinical setting. Resolution was evaluated by simulating the point-spread-functions (PSFs) and experimental measures on a phantom. RESULTS: All sequences were shown to have a similar SNR arbitrary units (AU) of 6-6.5 in brain white matter, 7-9 in gray matter and 17-18 AU in cerebrospinal fluid. SNR between white and gray matter were significantly different for KB and CN (p = 0.046 and <0.001 respectively), but not for SOS (p = 0.1). Group mean standard deviations were significantly smaller for CN (p = 0.016). Theoretical full-width at half-maximum linewidth of the PSF for CN is broadened by only 0.1, compared to 0.3 and 0.8 pixels for SOS and KB respectively. Actual image resolution is estimated as 8, 9 and 6.3 mm for SOS, KB and CN respectively. CONCLUSION: The CN sequence provides stronger tissue contrast than both SOS and KB, with more reproducible SNR measurements compared to KB. For CN, a higher true resolution in the same amount of time with no significant trade-off in SNR is achieved. CN is therefore more suitable for (23)Na-MRI in the brain.","Adult;Brain/ pathology;Female;Humans;Image Processing, Computer-Assisted/methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Phantoms, Imaging;Reproducibility of Results;Signal-To-Noise Ratio;Sodium/ chemistry","Riemer, F.;Solanky, B. S.;Stehning, C.;Clemence, M.;Wheeler-Kingshott, C. A.;Golay, X.",2014,Feb,10.1007/s10334-013-0395-2,0,
1690,Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer's disease,"Prior studies have identified white matter abnormalities in Alzheimer's disease (AD). Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity. Here, 108 normal older adults (age, 66-87) with assessments of apolipoprotein e4 (APOE4) genotype and assessment of amyloid burden by positron emission tomography underwent diffusion tensor imaging scans for measuring white matter integrity at 2 time points, on average 2.6 years apart. Linear mixed-effects models showed that amyloid burden at baseline was associated with steeper decline in fractional anisotropy in the parahippocampal cingulum (p < 0.05). This association was not significant between baseline measures suggesting that longitudinal analyses can provide novel insights that are not detectable in cross-sectional designs. Amyloid-related changes in hippocampus volume did not explain the association between amyloid burden and change in fractional anisotropy. The results suggest that accumulation of cortical amyloid and white matter changes in parahippocampal cingulum are not independent processes in individuals at increased risk for AD.",,"Rieckmann, A.;Van Dijk, K. R. A.;Sperling, R. A.;Johnson, K. A.;Buckner, R. L.;Hedden, T.",2016,1,,0,
1691,Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity,"Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. (c) 2015 Wiley Periodicals, Inc.",,"Rieckmann, A.;Hedden, T.;Younger, A. P.;Sperling, R. A.;Johnson, K. A.;Buckner, R. L.",2016,Feb,10.1002/hbm.23054,0,
1692,Neuropathological correlates of falling in the CC75C population-based sample of the older old,"BACKGROUND: Previous imaging studies have suggested links between brain pathologies and factors that are associated with falls such as gait, balance and daily function. Possible neuropathological correlates of older people's falls have been suggested based on brain imaging studies, but to date none have been examined in brain tissue. METHODS: Falls data collected from repeated surveys of a population-based cohort of individuals aged at least 75 years old at baseline were related to neuropathological data collected from post-mortem examination of the study's associated brain donor collection (n=212). RESULTS: Amongst people without dementia, most cerebrovascular neuropathological features examined, particularly white matter pallor, microinfarcts and microscopic atherosclerosis, were increasingly common across the subgroups categorised by no reports of falling, only one or at least two reports of falling. The overall burden of pathology was greater in those with dementia, but only microinfarcts showed a similar increase with respect to reported falling status. CONCLUSIONS: Subclinical pathologies sharing a common vascular origin are associated with increased falling amongst people with no dementia, as are microinfarcts in those with dementia. Although further research is needed to address the mechanisms of falls and their neuropathological correlates, the findings from the current study would suggest that if cerebrovascular disease prevention reduces vascular neuropathology changes this may have direct benefits in reducing falls amongst older people with or without dementia.","Accidental Falls/ statistics & numerical data;Aged, 80 and over;Autopsy;Brain/ pathology;Cerebrovascular Disorders/epidemiology;Cohort Studies;Female;Humans;Male","Richardson, K.;Hunter, S.;Dening, T.;Xuereb, J. H.;Matthews, F. E.;Brayne, C.;Fleming, J.",2012,Jul,,0,
1693,Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study,"BACKGROUND AND PURPOSE: White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. METHODS: A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. RESULTS: Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. CONCLUSIONS: Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.","Alzheimer Disease [pathology] [therapy];Cerebrovascular Disorders [pathology] [therapy];Disease Progression;Follow-Up Studies;Health Behavior;Magnetic Resonance Imaging;Nerve Fibers, Myelinated [pathology];Risk Factors;Aged[checkword];Aged, 80 and over[checkword];Humans[checkword];Sr-dementia","Richard, E.;Gouw, A. A.;Scheltens, P.;Gool, W. A.",2010,,10.1161/strokeaha.109.571281,0,
1694,Assessment of enlarged perivascular spaces and their relation to target organ damage and mild cognitive impairment in patients with hypertension,"Background and purpose: Enlarged perivascular spaces (EPVS) have been recently considered a feature of cerebral small vessel disease. They have been related to aging, hypertension and dementia but their relationship with hypertension related variables (i.e. target organ damage, treatment compliance) and mild cognitive impairment (MCI) is not fully elucidated. Our aims were to investigate the relation between basal ganglia (BG) and centrum semiovale (CSO) EPVS with vascular risk factors, hypertension related variables and MCI. Methods: In all, 733 hypertensive individuals free of stroke and dementia from the Investigating Silent Strokes in Hypertensives, a magnetic resonance imaging Study (ISSYS) underwent brain magnetic resonance imaging and cognitive testing to diagnose MCI or normal cognitive aging. Results: The numbers of participants presenting high grade (>10) EPVS at the BG and CSO were 23.3% and 40.0%, respectively. After controlling for vascular risk factors, high grade BG EPVS were associated with age (odds ratio 1.68; 95% confidence interval 1.37, 2.06), poor antihypertensive compliance (1.49; 1.03, 2.14) and the presence of microalbuminuria (1.95; 1.16, 3.28), whereas in the CSO only age (1.38; 1.18, 1.63) and male sex were associated with EPVS (1.73; 1. 24, 2.42). MCI was diagnosed in 9.3% of the participants and it was predicted by EPVS in the BG (1.87; 1.03, 3.39) but not in the CSO. This last association was greatly attenuated after correction for lacunes and white matter hyperintensities. Conclusions: Basal ganglia EPVS are associated with the presence of microalbuminuria and poor adherence to antihypertensive drugs. The BG EPVS relation with MCI is not independent of the presence of other cerebral small vessel disease markers.",antihypertensive agent;high density lipoprotein cholesterol;adult;article;basal ganglia enlarged perivascular space;blood pressure regulation;centrum semiovale enlarged perivascular space;cerebrovascular accident;cerebrovascular disease;cognitive aging;cognitive function test;confidence interval;controlled study;dementia;disease association;female;human;hypertension;major clinical study;male;microalbuminuria;mild cognitive impairment;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;observational study;perivascular space;priority journal;prospective study;risk factor;MRI scanner,"Riba-Llena, I.;Nafría, C.;Mundet, X.;López-Rueda, A.;Fernández-Cortiñas, I.;Jarca, C. I.;Jiménez-Balado, J.;Domingo, M.;Tovar, J. L.;Orfila, F.;Pujadas, F.;Álvarez-Sabín, J.;Maisterra, O.;Montaner, J.;Delgado, P.",2016,,10.1111/ene.12979,0,
1695,Assessment of enlarged perivascular spaces and their relation to target organ damage and mild cognitive impairment in patients with hypertension,"BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVS) have been recently considered a feature of cerebral small vessel disease. They have been related to aging, hypertension and dementia but their relationship with hypertension related variables (i.e. target organ damage, treatment compliance) and mild cognitive impairment (MCI) is not fully elucidated. Our aims were to investigate the relation between basal ganglia (BG) and centrum semiovale (CSO) EPVS with vascular risk factors, hypertension related variables and MCI. METHODS: In all, 733 hypertensive individuals free of stroke and dementia from the Investigating Silent Strokes in Hypertensives, a magnetic resonance imaging Study (ISSYS) underwent brain magnetic resonance imaging and cognitive testing to diagnose MCI or normal cognitive aging. RESULTS: The numbers of participants presenting high grade (>10) EPVS at the BG and CSO were 23.3% and 40.0%, respectively. After controlling for vascular risk factors, high grade BG EPVS were associated with age (odds ratio 1.68; 95% confidence interval 1.37, 2.06), poor antihypertensive compliance (1.49; 1.03, 2.14) and the presence of microalbuminuria (1.95; 1.16, 3.28), whereas in the CSO only age (1.38; 1.18, 1.63) and male sex were associated with EPVS (1.73; 1. 24, 2.42). MCI was diagnosed in 9.3% of the participants and it was predicted by EPVS in the BG (1.87; 1.03, 3.39) but not in the CSO. This last association was greatly attenuated after correction for lacunes and white matter hyperintensities. CONCLUSIONS: Basal ganglia EPVS are associated with the presence of microalbuminuria and poor adherence to antihypertensive drugs. The BG EPVS relation with MCI is not independent of the presence of other cerebral small vessel disease markers.",,"Riba-Llena, I.;Nafria, C.;Mundet, X.;Lopez-Rueda, A.;Fernandez-Cortinas, I.;Jarca, C. I.;Jimenez-Balado, J.;Domingo, M.;Tovar, J. L.;Orfila, F.;Pujadas, F.;Alvarez-Sabin, J.;Maisterra, O.;Montaner, J.;Delgado, P.",2016,Mar 10,10.1111/ene.12979,0,
1696,High daytime and nighttime ambulatory pulse pressure predict poor cognitive function and mild cognitive impairment in hypertensive individuals,"High blood pressure accelerates normal aging stiffness process. Arterial stiffness (AS) has been previously associated with impaired cognitive function and dementia. Our aims are to study how cognitive function and status (mild cognitive impairment, MCI and normal cognitive aging, NCA) relate to AS in a community-based population of hypertensive participants assessed with office and 24-hour ambulatory blood pressure measurements. Six hundred ninety-nine participants were studied, 71 had MCI and the rest had NCA. Office pulse pressure (PP), carotid-femoral pulse wave velocity, and 24-hour ambulatory PP monitoring were collected. Also, participants underwent a brain magnetic resonance to study cerebral small-vessel disease (cSVD) lesions. Multivariate analysis-related cognitive function and cognitive status to AS measurements after adjusting for demographic, vascular risk factors, and cSVD. Carotid-femoral pulse wave velocity and PP at different periods were inversely correlated with several cognitive domains, but only awake PP measurements were associated with attention after correcting for confounders (beta = -0.22, 95% confidence interval (CI) -0.41, -0.03). All ambulatory PP measurements were related to MCI, which was independently associated with nocturnal PP (odds ratio (OR) = 2.552, 95% CI 1.137, 5.728) and also related to the presence of deep white matter hyperintensities (OR = 1.903, 1.096, 3.306). Therefore, higher day and night ambulatory PP measurements are associated with poor cognitive outcomes.","Aged;Aging/psychology;Blood Pressure/*physiology;Blood Pressure Monitoring, Ambulatory/*methods;Brain/blood supply/pathology;Cerebral Small Vessel Diseases/pathology/physiopathology/*psychology;Cognition Disorders/pathology/physiopathology/*psychology;Female;Humans;Hypertension/pathology/physiopathology/*psychology;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Vascular Stiffness/*physiology","Riba-Llena, I.;Nafria, C.;Filomena, J.;Tovar, J. L.;Vinyoles, E.;Mundet, X.;Jarca, C. I.;Vilar-Bergua, A.;Montaner, J.;Delgado, P.",2016,Jan,10.1038/jcbfm.2015.90,0,
1697,Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design,"BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.",Analysis of Variance;Blood Pressure [physiology];Brain Infarction [pathology];Cognition Disorders [diagnosis] [etiology];Cohort Studies;Hypertension [complications] [epidemiology];Magnetic Resonance Imaging;Physical Examination;Risk Factors;Stroke [complications] [diagnosis] [epidemiology] [prevention & control];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword],"Riba-Llena, I.;Jarca, C. I.;Mundet, X.;Tovar, J. L.;Orfila, F.;López-Rueda, A.;Nafría, C.;Fernández, J. L.;Castañé, X.;Domingo, M.;Alvarez-Sabín, J.;Fernández-Cortiñas, I.;Maisterra, O.;Montaner, J.;Delgado, P.",2013,,10.1186/1471-2377-13-130,0,
1698,MRI Visual Ratings of Brain Atrophy and White Matter Hyperintensities across the Spectrum of Cognitive Decline Are Differently Affected by Age and Diagnosis,"Aim: To assess the associations of age and diagnosis with visual ratings of medial temporal lobe atrophy (MTA), parietal atrophy (PA), global cortical atrophy (GCA), and white matter hyperintensities (WMH) and to investigate their clinical value in a large memory clinic cohort. Methods: We included 2,934 patients (age 67 +/- 9 years; 1,391 [47%] female; MMSE 24 +/- 5) from the Amsterdam Dementia Cohort (1,347 dementia due to Alzheimer's disease [AD]; 681 mild cognitive impairment [MCI]; 906 controls with subjective cognitive decline). We analyzed the effect of age, APOE e4 and diagnosis on visual ratings using linear regression analyses. Subsequently, we compared diagnostic and predictive value in three age-groups (<65 years, 65-75 years, and >75 years). Results: Linear regression analyses showed main effects of age and diagnosis and an interaction age(*)diagnosis for MTA, PA, and GCA. For MTA the interaction effect indicated steeper age effects in MCI and AD than in controls. PA and GCA increased with age in MCI and controls, while AD patients have a high score, regardless of age. For WMH we found a main effect of age, but not of diagnosis. For MTA, GCA and PA, diagnostic value was best in patients <65 years (optimal cut-off: >/=1). PA and GCA only discriminated in patients <65 years and MTA in patients <75 years. WMH did not discriminate at all. Taking into account APOE did not affect the identified optimal cut-offs. When we used these scales to predict progression in MCI using Cox proportional hazard models, only MTA (cut-off >/=2) had any predictive value, restricted to patients >75 years. Conclusion: Visual ratings of atrophy and WMH were differently affected by age and diagnosis, requiring an age-specific approach in clinical practice. Their diagnostic value seems strongest in younger patients.",Alzheimer's disease;Mri;diagnostic test assessment;mild cognitive impairment (MCI);prognosis,"Rhodius-Meester, H. F. M.;Benedictus, M. R.;Wattjes, M. P.;Barkhof, F.;Scheltens, P.;Muller, M.;van der Flier, W. M.",2017,,,0,
1699,Correspondence regarding: A novel cerebral microangiopathy with endothelial cell atypia and multifocal white matter lesions: A direct mycoplasmal infection? J Neuropathol Exp Neurol 2007;66: 1100-17,,adult;agitation;autopsy;brain biopsy;brain disease;brain hypoxia;case report;cerebral microangiopathy;cognitive defect;computer assisted tomography;dementia;electroencephalogram;electron microscopy;endothelial cell atypia;gliosis;human;human tissue;immunohistochemistry;laboratory test;letter;male;microangiopathy;mortality;mycoplasmosis;myoclonus;nerve cell lesion;nuclear magnetic resonance imaging;priority journal;saccadic eye movement;seizure;tremor;white matter lesion,"Rhodes, R. H.;Anderson, B. A.",2012,,,0,
1700,Periventricular white matter lucencies in senile dementia of the Alzheimer type and in normal aging,"The significance of periventricular lucencies in the white matter on CT in demented patients is not understood. We studied the relationship of these changes to mental status of subjects with senile dementia of the Alzheimer type. A semiquantitative method showed more numerous and extensive lucencies in demented than in healthy elderly. Neuropathologic examination of five subjects with these changes and confirmed Alzheimer's disease revealed diffuse white matter pallor without infarction. There were no hypertensive vascular changes, although limited hyaline thickening was present.","Aged;Aging/*pathology;Alzheimer Disease/*pathology/radiography;Brain/*pathology/radiography;Cerebral Ventricles/pathology;Female;Humans;Longitudinal Studies;Male;Tomography, X-Ray Computed","Rezek, D. L.;Morris, J. C.;Fulling, K. H.;Gado, M. H.",1987,Aug,,0,
1701,"Expression of cellular prion protein in the frontal and occipital lobe in Alzheimer's disease, diffuse Lewy body disease, and in normal brain: An immunohistochemical study","Cellular prion protein (PrP(c)) is a glycoprotein expressed at low to moderate levels within the nervous system. Recent studies suggest that PrP(c) may possess neuroprotective functions and that its expression is upregulated in certain neurodegenerative disorders. We investigated whether PrP(c) expression is altered in the frontal and occipital cortex in two well-characterized neurodegenerative disorders-Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)-compared with that in normal human brain using immunohistochemistry and computerized image analysis. The distribution of PrP(c) was further tested for correlation with glial reactivity. We found that PrP(c) was localized mainly in the gray matter (predominantly in neurons) and expressed at higher levels within the occipital cortex in the normal human brain. Image analysis revealed no significant variability in PrP(c) expression between DLBD and control cases. However, blood vessels within the white matter of DLBD cases showed immunoreactivity to PrP(c). By contrast, this protein was differentially expressed in the frontal and occipital cortex of AD cases; it was markedly overexpressed in the former and significantly reduced in the latter. Epitope specificity of antibodies appeared important when detecting PrP (c). The distribution of PrP(c) did not correlate with glial immunoreactivity. In conclusion, this study supports the proposal that regional changes in expression of PrP(c) may occur in certain neurodegenerative disorders such as AD, but not in Other disorders such as DLBD. © The Histochemical Society, Inc.",,"Rezaie, P.;Pontikis, C. C.;Hudson, L.;Cairns, N. J.;Lantos, P. L.",2005,August,,0,
1702,Apathy: a major symptom in CADASIL,"OBJECTIVE: The frequency and impact of apathy in subcortical ischemic vascular dementia (SIVD) remain undetermined. The frequency, clinical, neuropsychological, and imaging correlates of apathy were assessed in a large cohort of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetic model of SIVD. METHODS: Apathy was diagnosed based on Neuropsychiatric Inventory assessment. Degree of disability was assessed by modified Rankin scale, cognitive impairment by Mattis Dementia Rating Scale (MDRS) and Mini-Mental State Examination (MMSE), autonomy by the Instrumental Activities of Daily Living (IADL) scale, and quality of life by SEP-59 self-questionnaire. Validated imaging methods were used to determine the total burden of cerebral lesions. RESULTS: Among 132 patients, 54 (41%) were apathetic. Apathetic patients were older than nonapathetic subjects, had a lower MMSE and MDRS score, had more global disability, and were more limited in IADL. Apathetic patients were more frequently depressed compared to nonapathetic patients and more frequently presented additional neuropsychiatric symptoms. Multiple regression modeling showed a significant and independent association between apathy and a lower score of overall quality of life and between apathy and a higher load of white matter and lacunar lesions. CONCLUSIONS: The results suggest that apathy is common in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), appears in association with cognitive impairment, global functional disability, and severe neuropsychiatric symptoms during the course of the disease, and can occur separately from depression. Apathy has an independent impact on the overall quality of life in CADASIL.","Adult;Affect/ physiology;Aged;CADASIL/ pathology/ psychology;Cohort Studies;Dementia, Vascular/pathology/psychology;Depression/psychology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prospective Studies;Psychiatric Status Rating Scales;Quality of Life","Reyes, S.;Viswanathan, A.;Godin, O.;Dufouil, C.;Benisty, S.;Hernandez, K.;Kurtz, A.;Jouvent, E.;O'Sullivan, M.;Czernecki, V.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2009,Mar 10,10.1212/01.wnl.0000344166.03470.f8,0,
1703,Encephalitis in cat scratch disease with persistent dementia,Encephalitis in cat scratch disease is uncommon and usually reversible. The patient with cognitive impairment and severe memory disorder did not improve after a 30 month follow up. MRI revealed disseminated lesions in the white matter of the cerebral hemispheres.,"Anti-Bacterial Agents;Cat-Scratch Disease/*complications;Cognition Disorders/complications/diagnosis/etiology;Dementia/diagnosis/*etiology;Drug Therapy, Combination/therapeutic use;Electroencephalography;Encephalitis/diagnosis/*etiology/radiography;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/diagnosis/etiology;Middle Aged;Tomography, X-Ray Computed","Revol, A.;Vighetto, A.;Jouvet, A.;Aimard, G.;Trillet, M.",1992,Feb,,0,
1704,Pathological findings correlated with magnetic resonance imaging in subcortical arteriosclerotic encephalopathy (Binswanger's disease),"Formalin-fixed brain slices from four cases of subcortical arteriosclerotic encephalopathy in which a firm diagnosis could be made both clinically and pathologically have been studied by magnetic resonance imaging (MRI). The slices were subsequently embedded in paraffin-wax or celloidin and sections were cut in the same plane as the MRI slices. There was a good correlation between the extent and severity of the abnormal MRI signal and the pathological changes. Areas of diffuse MRI abnormality corresponded with areas of axonal and myelin loss with gliosis, and small 'lacune'-like lesions corresponded with lacunar infarcts histologically. Sparing of the subcortical U-fibres was seen histologically and on MRI. The abnormal signal probably originates from increased tissue water attributable to gliosis and an expanded extracellular space.",,"Revesz, T.;Hawkins, C. P.;Du Boulay, E. P. G. H.;Barnard, R. O.;McDonald, W. I.",1989,1989,,0,
1705,Development of Cerebral Microbleeds in the APP23-Transgenic Mouse Model of Cerebral Amyloid Angiopathy-A 9.4 Tesla MRI Study,"BACKGROUND: Cerebral amyloid angiopathy (CAA) is characterized by extracellular deposition of amyloid beta (Abeta) around cerebral arteries and capillaries and leads to an increased risk for vascular dementia, spontaneous lobar hemorrhage, convexal subarachnoid hemorrhage, and transient focal neurological episodes, which might be an indicator of imminent spontaneous intracerebral hemorrhage. In CAA cerebral microbleeds (cMBs) with a cortical/juxtacortical distribution are frequently observed in standard magnetic resonance imaging (MRI). In vivo MRI of transgenic mouse models of CAA may serve as a useful tool to investigate translational aspects of the disease. MATERIALS AND METHODS: APP23-transgenic mice demonstrate cerebrovascular Abeta deposition with subsequent neuropathological changes characteristic for CAA. We performed a 9.4 Tesla high field MRI study using T2, T2* and time of flight-magnetic resonance angiograpy (TOF-MRA) sequences in APP23-transgenic mice and wildtype (wt) littermates at the age of 8, 12, 16, 20 and 24 months, respectively. Numbers, size, and location of cMBs are reported. RESULTS: T2* imaging demonstrated cMBs (diameter 50-300 mum) located in the neocortex and, to a lesser degree, in the thalamus. cMBs were detected at the earliest at 16 months of age. Numbers increased exponentially with age, with 2.5 +/- 2 (median +/- interquartilrange) at 16 months, 15 +/- 6 at 20 months, and 31.5 +/- 17 at 24 months of age, respectively. CONCLUSION: We report the temporal and spatial development of cMBs in the aging APP23-transgenic mouse model which develops characteristic pathological patterns known from human CAA. We expect this mouse model to serve as a useful tool to non-invasively monitor mid- and longterm translational aspects of CAA and to investigate experimental therapeutic strategies in longitudinal studies.",App23;Caa;Mri;amyloid;cerebral microbleeds;transgenic mice,"Reuter, B.;Venus, A.;Heiler, P.;Schad, L.;Ebert, A.;Hennerici, M. G.;Grudzenski, S.;Fatar, M.",2016,,10.3389/fnagi.2016.00170,0,
1706,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL),"Background. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuco-encephalopathy (CADASIL) is a hereditary autosomal dominant non-atherosclerotic non-amyloid cerebral arteriopathy. The disease was identified in 1993. We are not aware of reports in the literature of its occurrence in South Africa, and we present the clinical and laboratory features of 5 patients with CADASIL. Methods. Patients with the characteristic radiological white matter disease and typical features (family history, ischaemic events, migraine or dementia) were evaluated for possible CADASIL by means of clinical examination, routine investigations for strokes, magnetic resonance imaging, skin biopsy electron microscopy, evoked potentials and electro-encephalography. Results. The clinical and laboratory features of our study largely correlate with reported studies. However, all of the skin biopsies were positive, and the onset of migraine in our patients was considerably earlier. A new finding, to our knowledge, was the normality of visual, somatosensory and auditory evoked potentials. Conclusion. Our study confirms the existence of CADASIL in South Africa, and also suggests that skin electron microscopy is useful, despite recent reports of its low sensitivity, and that evoked potentials in CADASIL are likely to be normal.",,"Retief, C.;Schutte, C. M.;Baker, M. K.",2009,2009,,0,
1707,One-year age changes in MRI brain volumes in older adults,"Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia.","Age Factors;Aged;Aged, 80 and over;Aging/ pathology;Brain/blood supply/ pathology/radionuclide imaging;Cerebrovascular Circulation;Cognition Disorders/pathology;Cross-Sectional Studies;Female;Health Status;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory Disorders/pathology;Middle Aged;Neuropsychological Tests;Regression Analysis;Sex Factors;Tomography, Emission-Computed","Resnick, S. M.;Goldszal, A. F.;Davatzikos, C.;Golski, S.;Kraut, M. A.;Metter, E. J.;Bryan, R. N.;Zonderman, A. B.",2000,May,,0,
1708,Integrity of white matter structure is related to episodic memory performance in the low-educated elderly,"The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. METHODS: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 +/- 3.8 years, with 2.2 +/- 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. RESULTS: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. CONCLUSIONS: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.","Aged;Aged, 80 and over;Diffusion Tensor Imaging;Educational Status;Female;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/ diagnostic imaging/etiology/pathology;Neuropsychological Tests;White Matter/ diagnostic imaging/pathology","Resende, E. P. F.;Tovar-Moll, F. F.;Ferreira, F. M.;Bramati, I.;de Souza, L. C.;Carmona, K. C.;Guimaraes, H. C.;Carvalho, V. A.;Barbosa, M. T.;Caramelli, P.",2017,Nov,,0,
1709,Ischemic cerebrovascular burden evaluated by magnetic resonance imaging in an elderly Brazilian community: The Pieta study,"In developing countries, cardiovascular risk factors are poorly controlled, leading to high prevalence of cerebrovascular diseases. The aim of the study was to evaluate the burden of white matter lesions in magnetic resonance through the Fazekas scale in a population aged 75 + years living in the community, and to investigate possible associations between vascular lesions, cardiovascular risk factors and cognitive status. Subjects were selected from a community-based study on brain aging conducted in Caete (Minas Gerais state), Brazil. Overall, 177 participants (112 cognitively healthy, 36 with cognitive impairment-no dementia and 29 with dementia), being 108 women, aged 79.3 +/- 3.8 years, with 3.1 +/- 2.9 years of educational level, underwent a 3 Tesla magnetic resonance scanner with fluid attenuated image recovery acquisition. Severity of white matter lesions was assessed through the Fazekas scale. Severe white matter lesions were present in 31.1% of the whole sample and in 25.0% of the cognitively healthy individuals. A significant association was found between severe white matter lesions and cognitive impairment (OR = 2.20, 95% CI 1.17-6.53; p = 0.021), as well as with hypertension (OR = 1.92, 95% CI 1.03-7.39; p = 0.043). In conclusion, a high prevalence of severe white matter lesions was observed in this elderly Brazilian population sample, and white matter lesions were associated with hypertension and cognitive status. Importantly, the prevalence of white matter lesions was also high in cognitively healthy subjects.","AD, Alzheimer's disease;Aging;CIND, cognitive impairment-no dementia;Dementia;FAQ, Functional Activity Questionnaire;FLAIR, fluid attenuated inversion recovery;Hypertension;MMSE, Mini-Mental Status Examination;MRI, magnetic resonance imaging;SVD, small vessel disease;WMH, white matter hyperintensities;White matter lesions","Resende, E. P. F.;Costa-Silva, L.;Carmona, K. C.;Machado, T. H.;Machado, J. C. B.;Guimaraes, H. C.;Barbosa, M. T.;Teixeira, A. L.;Cruz de Souza, L.;Caramelli, P.",2016,Dec,,0,
1710,Ischemic cerebrovascular burden evaluated by magnetic resonance imaging in an elderly Brazilian community: The Pietà study,"In developing countries, cardiovascular risk factors are poorly controlled, leading to high prevalence of cerebrovascular diseases. The aim of the study was to evaluate the burden of white matter lesions in magnetic resonance through the Fazekas scale in a population aged 75 + years living in the community, and to investigate possible associations between vascular lesions, cardiovascular risk factors and cognitive status. Subjects were selected from a community-based study on brain aging conducted in Caeté (Minas Gerais state), Brazil. Overall, 177 participants (112 cognitively healthy, 36 with cognitive impairment-no dementia and 29 with dementia), being 108 women, aged 79.3 ± 3.8 years, with 3.1 ± 2.9 years of educational level, underwent a 3 Tesla magnetic resonance scanner with fluid attenuated image recovery acquisition. Severity of white matter lesions was assessed through the Fazekas scale. Severe white matter lesions were present in 31.1% of the whole sample and in 25.0% of the cognitively healthy individuals. A significant association was found between severe white matter lesions and cognitive impairment (OR = 2.20, 95% CI 1.17–6.53; p = 0.021), as well as with hypertension (OR = 1.92, 95% CI 1.03–7.39; p = 0.043). In conclusion, a high prevalence of severe white matter lesions was observed in this elderly Brazilian population sample, and white matter lesions were associated with hypertension and cognitive status. Importantly, the prevalence of white matter lesions was also high in cognitively healthy subjects.",age distribution;aged;article;brain ischemia;Brazilian;cardiovascular risk;cognition;cognitive defect;community living;controlled clinical trial;controlled study;dementia;diabetes mellitus;disease association;disease severity;educational status;female;human;hypertension;major clinical study;male;neuroimaging;nuclear magnetic resonance;priority journal;vascular lesion;white matter lesion,"Resende, E. D. P. F.;Costa-Silva, L.;Carmona, K. C.;Machado, T. H.;Machado, J. C. B.;Guimarães, H. C.;Barbosa, M. T.;Teixeira, A. L.;Cruz de Souza, L.;Caramelli, P.",2016,,10.1016/j.ensci.2016.11.011,0,
1711,White matter integrity and late-life depression in community-dwelling individuals: Diffusion tensor imaging study using tract-based spatial statistics,"Background: Late-life depression has been associated with white matter changes in studies using the regions of interest approach. Aims: To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics. Method: The sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression. Results: Individuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up. Conclusions: Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.",,"Reppermund, S.;Zhuang, L.;Wen, W.;Slavin, M. J.;Trollor, J. N.;Brodaty, H.;Sachdev, P. S.",2014,1,,0,
1712,Treatment of Susac's Syndrome,"Susac's syndrome (SS) consists of the triad of encephalopathy, branch retinal artery occlusions (BRAO), and hearing loss. It usually affects women aged 20 to 40, but men are also affected, and the age range extends from 9 to 72 years. It tends to be unrecognized, even in major academic centers. The complete triad may not be present at the onset, which makes diagnosis more difficult. However, since this disorder is treatable, early diagnosis is important. The encephalopathy is usually associated with headaches, multifocal neurologic manifestations, and psychiatric features (particularly paranoia). MRI shows a white matter disturbance that is frequently confused with multiple sclerosis and acute disseminated encephalomyelitis. During the encephalopathy, the corpus callosum is always affected and shows central involvement--small to large ""snowballs"" and linear defects, ""spokes."" As the acute changes (microinfarcts) resolve, central callosal ""holes"" develop, a pathognomonic finding. The deep gray matter (70%) and leptomeninges (33%) also may be involved. Dilated fundus examination will reveal branch retinal artery occlusions. Fluorescein angiography may disclose pathognomonic staining of the arterioles proximal to the occlusions and of nonoccluded arterioles. The cochlear hearing loss, sometimes associated with vertigo, is usually bilateral, and deafness becomes a major disabling problem. Brain biopsies, anatomic observations, and responses to immunosuppressive therapy suggest that SS represents an autoimmune endotheliopathy in the microvasculature of the brain, retina, and cochlea. Treatment requires immunosuppression. High-dose corticosteroid therapy is the mainstay, but additional therapies such as intravenous immunoglobulin, mycophenolate mofetil, and cyclophosphamide are often necessary. Rituximab is the newest therapy to consider. Treatment should be prompt, aggressive, and sustained to avoid the dreaded residuals of dementia, deafness, and blindness.",,"Rennebohm, R. M.;Egan, R. A.;Susac, J. O.",2008,Jan,,0,
1713,Cognitive Impairment After Stroke,"BACKGROUND: Vascular dementia is extremely common and contributes to stroke-associated morbidity and mortality. The study of vascular dementia may help to plan preventive interventions. AIMS: To study the frequency of cognitive impairment after stroke in a series of consecutive patients with acute stroke, along with factors which influence it. METHODS: Fifty adults with acute infarct or hemorrhage (as seen on computed tomography of the brain) were included in the study. The National Institute of Health Stroke Scale (NIHSS) and Barthel's Index scores were done. Cognitive testing was done by PGI Battery of Brain Dysfunction (PGI-BBD) and Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (SIQCODE). Statistical analysis was by Student's t-test, Chi-square test, Fisher's exact test, and Mann-Whitney U test. RESULTS: Mean age of patients was 61.82 years; males and ischemic strokes predominated. Dementia was seen in 30%, cognitive impairment no dementia (CIND) in 42%, and normal cognition in 28% patients. Factors associated with vascular cognitive impairment included old age, male sex, low education, hemorrhages, recurrent or severe stroke, silent infarcts, severe cortical atrophy, and left hemispheric or subcortical involvement. CONCLUSIONS: Up to 72% of patients have some form of cognitive impairment after a stroke. Secondary stroke prevention could reduce the incidence of vascular dementia.",barthel index;cind;cognitive impairment;iqcode;nihss;psd;stroke;vascular dementia,"Renjen, P. N.;Gauba, C.;Chaudhari, D.",2015,,10.7759/cureus.335,0,
1714,Radiation therapy-related ataxia associated with FDG-PET cerebellar hypometabolism,"Brain FDG-PET after radiation therapy is classically used to differentiate between tumor recurrence and radiation-related tumor necrosis. Little is known about FDG-PET in patients with radiation-induced leuko - encephalopathy without radiological aspect of necrosis. We present a 69-year-old woman who had preventive whole brain radiation after a diagnosis of paraneoplastic Lambert-Eaton syndrome related to small cell lung cancer. Five months after radiation therapy, she developed radiation-induced leukoencephalopathy manifested by ataxia. Profound cerebellar hypometabolism on FDGPET was in contrast with the presence of only discrete cerebellar white matter changes on MRI. FDG-PET abnormalities seem to correlate better with clinical signs related to radiation-associated brain toxicity than MRI.",amifampridine;amphiphysin;cisplatin;corticosteroid;etoposide;fluorodeoxyglucose f 18;voltage gated calcium channel;aged;article;ataxia;brain radiation;case report;cerebellum disease;cerebellum hypometabolism;drug megadose;Eaton Lambert syndrome;female;human;human cell;human tissue;leukoencephalopathy;limb weakness;small cell lung cancer;lymph node;lymph node biopsy;mental deterioration;nerve conduction;nerve stimulation;nuclear magnetic resonance imaging;positron emission tomography;tendon reflex;vertigo;weight reduction;xerostomia,"Renard, D.;Collombier, L.;Castelnovo, G.;Fourcade, G.;Debrigode, C.;Labauge, P.",2010,,,0,
1715,Clinical and radiological characteristics in multiple sclerosis patients with large cavitary lesions,"Background: Large cavitary lesions are not typical for multiple sclerosis (MS). Cavitary white matter changes may be seen in megalencephalic leukoencephalopathy with subcortical cysts, Alexander disease, mitochondrial leukoencephalopathies, vanishing white matter disease, leukoencephalopathy with calcifications and cysts, cytomegalovirus infection, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Objective: To analyze clinical and radiological characteristics in MS patients with large cavitary lesions. Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), Mini Mental State (MMS), corpus callosum lesions, history of segmental myelitis, CSF oligoclonal bands (OCB), visual evoked potentials (VEP), vanishing white matter disease genetic analysis, and characteristics of the cavitary lesions were analyzed. Results: Nine patients were analyzed, 1 man and 8 women. Mean age of disease onset was 38.5 years. Mean disease duration was 9 years. Three patients had initial relapsing-remitting MS and 6 patients had primary-progressive MS. Mean EDSS was 4.5. Mean MMS was 20/30. Segmental myelitis was present in 6 cases. OCB were found in 6 patients. VEP was performed in 6 patients, and pathological in all but one. Vanishing white matter disease genetic analysis was performed and negative in 5 patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance. Conclusion: MS patients with large cavitary lesions seem to represent an MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction. © 2012 S. Karger AG, Basel.",oligoclonal band;adolescent;adult;Alexander disease;article;brain calcification;brain damage;CADASIL;clinical article;clinical assessment;clinical feature;corpus callosum;disease duration;evoked visual response;Expanded Disability Status Scale;female;genetic analysis;human;male;Mini Mental State Examination;multiple sclerosis;nuclear magnetic resonance imaging;onset age;priority journal;radiodiagnosis;white matter lesion,"Renard, D.;Brochet, B.;Vukusic, S.;Edan, G.;Deburghgraeve, V.;Goizet, C.;Dupuy, D.;Touze, E.;Deschamps, R.;Zephyr, H.;Creange, A.;Castelnovo, G.;Boespflug-Tanguy, O.;Labauge, P.",2012,,,0,
1716,"Analysis of clinical, imaging and genetic mutations of 37 cases of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy from 19 pedigrees","Objective: To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China. Methods: CADASIL patients diagnosed by gene or biopsy in People's Hospital of Zhengzhou University between 2012-2016 were recruited. Clinical and imaging features of these patients were analyzed retrospectively. The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time. Results: There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL. Two families were confirmed by pathological examination and 17 by genetic testing. Of these 17 families, 13 mutations were found. Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families. Mutation in exons 3, 8 and 20 was detected in one family respectively. Most patients presented with stroke and several presented with cognitive decline. Twelve patients had been attacked by risk factors. Magnetic resonance imaging (MRI) was performed on 22 patients. White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule. There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI. Conclusions: CADASIL patients can be associated with risk factors. T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external. Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.",Notch3 receptor;article;basal ganglion;biopsy;brain region;brain stem;CADASIL;cerebrovascular accident;China;clinical article;diagnostic imaging;exon;external capsule;gene mutation;genetic screening;human;human tissue;nuclear magnetic resonance imaging;pedigree;retrospective study;risk factor;subcortical;temporal pole;white matter lesion,"Ren, Z.;Shi, Y.;Chen, Z.;Xia, M.;Wang, W.;Liu, J.;Liu, H.;Chen, S.;Zhou, Y.;Huang, Y.;Xiang, L.;Zhang, J.",2017,,10.3760/cma.j.issn.1006-7876.2017.08.010,0,
1717,"[CADASIL with clinical manifestations of baldness, lumbago and Parkinson's symptoms]","OBJECTIVE: To investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms. METHODS: Clinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing. RESULTS: The symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives. CONCLUSION: CADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.",,"Ren, Z.;Chen, S.;Shi, Y.;Zhang, Y.;Wang, W.;Chen, Z.;Xia, M.;Shi, X.;Zhang, J.",2017,Dec 10,,0,
1718,"[Effects of Tongluo Xingnao effervescent tablets on blood rheology, iNOS, VEGF and LDH-5 in MID rats]","The study was to explore effects of Tongluo Xingnao effervescent tablets on the blood rheology, iNOS, VEGF and LDH-5 in multi-infarct dementia(MID) model rats. Establish MID model rats were induced by microthrombosis, from which 50 successful model rats were randomly divided into five groups, such as the model control group, the dihydroergotoxine mesylate tablets(hydergine) group(0.7 mg*kg(-)(1)), Tongluo Xingnao effervescent tablets high-dose, medium-dose and low-dose groups(7.56, 3.78, 1.89 g*kg(-)(1)). Another ten rats in the sham group were randomly selected as the parallel control group. Each group was orally administered with drugs for 90 days. The learning and memory ability was evaluated with the Morris water maze test, while the whole blood viscosity and the erythrocyte aggregation index derived from abdominal aorta were measured in different shear rates. In addition, the levels of VEGF and iNOS in the serum were determined by ELISA kits. The expression of LDH-5 in hippocampus of rats was measured with immunohistochemistry and image quantitative analysis. The result showed that Tongluo Xingnao effervescent tablets notably decreased the escape latency of MID model rats, increased times of entering into the escape platform and prolonged retention time in medium ring, meanwhile the whole blood viscosity in MID model rats was also notably reduced in four shear rates, i.e. 1, 5, 30, 200 S(-)(1), erythrocyte aggregation index, serum VEGF and iNOS, and average optical density value of LDH-5, with a statistically significant differences compared with the model control group (P<0.05). In conclusion, Tongluo Xingnao effervescent tablets could improve the ability of learning and memory of MID model rats and the blood rheology, reduce the level of iNOS, VEGF and the expression of LDH-5, and then improved the brain energy supply.",Ldh-5;Tongluo Xingnao effervescent tablets;Vegf;blood rheology;iNOS;multi-infarct dementia;relevant financial relationships with commercial interests to disclose.,"Ren, X. Y.;Hu, Y.;Wei, J. P.;Fu, W. J.;Xu, S. J.;Wang, Y. Y.",2016,Mar,,0,
1719,White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance,"White matter tract alterations have been consistently described in Alzheimer's disease (AD). In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011) (n = 22) and healthy controls (n = 15). Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA) and increase of radial diffusivity (RD) in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Atrophy/pathology;Diffusion Tensor Imaging;Female;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted;Male;Memory, Episodic;Mild Cognitive Impairment/ pathology;Neural Pathways/pathology;Prodromal Symptoms;White Matter/ pathology","Remy, F.;Vayssiere, N.;Saint-Aubert, L.;Barbeau, E.;Pariente, J.",2015,,10.1016/j.nicl.2015.01.014,0,
1720,Hereditary dementia with intracerebral hemorrhages and cerebral amyloid angiopathy,"BACKGROUND: Deposition of the beta-amyloid peptide (Abeta) in neuritic plaques is a hallmark of Alzheimer disease (AD). Mutations in genes encoding amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1, PSEN2) are associated with increased accumulation of Abeta in neuritic plaques or in the walls of cerebral vessels. Intracerebral hemorrhage occasionally affects patients with AD. METHODS: A Finnish family with dementia in four generations and with frequent co-occurrence of dementia and intracerebral hemorrhage was identified. Clinical features of 14 family members with a cognitive decline were evaluated. All exons in genes encoding APP, PSEN1, PSEN2, cystatin C, transthyretin, gelsolin, and ITM2B were sequenced, and an association study of APP was conducted by identification of single-nucleotide polymorphisms. RESULTS: Neuropathologic examination revealed Alzheimer-type changes with Abeta in neuritic plaques and vessel walls, but the cognitive profile of the patients differed from that in AD, as the visuoconstructive functions and verbal fluency were well preserved even in the moderate stage of the disease. In addition to cognitive decline, five patients had had lobar intracerebral hemorrhages and one was diagnosed with hemosiderin deposits in MRI, suggesting previous cerebral microbleeds. No causative mutations were identified in candidate genes associated with amyloid diseases, but linkage to APP region could not be entirely excluded. CONCLUSIONS: The family presents an autosomal dominant form of beta-amyloidogenic disease that resembles the Italian, Flemish, and Iowa types of AD. No amyloidogenic mutations were identified, but the role of the APP region could not be entirely excluded.","Adult;Age of Onset;Alzheimer Disease/classification/diagnosis/psychology;Biopsy;Brain/pathology/radiography/radionuclide imaging;Brain Chemistry;Cerebral Amyloid Angiopathy/*epidemiology/genetics/pathology/radiography;Cerebral Hemorrhage/*epidemiology/genetics/pathology/radiography;DNA Mutational Analysis;Dementia/diagnosis/*epidemiology/genetics/pathology/psychology/radiography;Diagnosis, Differential;Female;Finland;Genes, Dominant;Genetic Heterogeneity;Haplotypes/genetics;Hemosiderin/analysis;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Pedigree;Plaque, Amyloid;Polymorphism, Restriction Fragment Length;Polymorphism, Single Nucleotide;Positron-Emission Tomography;Tomography, X-Ray Computed","Remes, A. M.;Finnila, S.;Mononen, H.;Tuominen, H.;Takalo, R.;Herva, R.;Majamaa, K.",2004,Jul 27,,0,
1721,Vascular parkinsonism - an update,"Vascular parkinsonism (VP) is a heterogeneous clinical entity. The idea of a relationship between cerebral vascular disease and parkinsonism may be traced back to the 1920s, when the diagnostic unit called ""arteriosclerotic parkinsonism"", a predecessor of VP, was established. This review is concerned with historical and contemporary views regarding the possible vascular genesis of parkinsonism. Confusion persists as a result of vaguely defined diagnostic criteria. The following types of simultaneous occurrence of parkinsonism and cerebral vascular disease (CVD) may be recognised:1.gait disorders of the lower body parkinsonism type are caused mostly by white matter lesions in the frontal lobes; such disorders may require a diagnosis of vascular origin. We suggest replacing the term ""lower body parkinsonism"" with a more appropriate term not including the word ""parkinsonism"": an alternative term could be ""cerebrovascular gait disorder"";2.if the signs and symptoms are typical for idiopathic Parkinson's disease (IPD), the coincidence of IPD and CVD should be considered;3.if the symptoms of parkinsonism are neither typical for IPD nor for VP, and there are clinical or MR signs of CVD, VP should be regarded as possible when alternative causes are excluded;4.if the symptoms of parkinsonism and clinical and MR signs are typical for VP, VP should be regarded as probable;5.if a stroke affecting the contralateral basal ganglia is followed by the occurrence of hemiparkinsonism, the diagnosis of VP is unambiguous. Vascular parkinsonism (VP) is probably one of the most frequently erroneous neurological diagnoses. The reason for this misdiagnosis is that both cerebral vascular disease (CVD) and parkinsonism usually occur at the same age. Due to the high incidence of CVD, it is possible for CVD and idiopathic Parkinson's disease (IPD) to coincide in some cases. Another reason for the misdiagnosis is that the concept of VP lacks clarity. This review aims to contribute to an improved understanding of VP in clinical practice. In this context, the term ""CVD"" is understood in the broad sense of a brain impairment caused by cerebral vessel pathology. It covers various concepts, as some authors use the term CVD to mean a manifestation of vascular lesions in pathologico-anatomical material or in the imaging techniques; others mean the history and clinical manifestation of cerebral ischaemia, or, more rarely, haemorrhage. The term CVD may cover large vessel disease as well as small vessel disease. This means that territorial and lacunar infarcts and white matter lesions (WML) are all considered as CVD. © 2006 Elsevier B.V. All rights reserved.",,"Rektor, I.;Rektorová, I.;Kubová, D.",2006,25,,0,
1722,Neuroimaging and neurocognitive abnormalities associated with bipolar disorder in old age,"Objectives Cognitive dysfunction is prevalent in older adults with bipolar disorder (BD). High white matter hyperintensity (WMH) burden, a marker of white matter disease, detected on T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) has been consistently reported in BD across all age ranges, including older adults. Yet, whether high WMH burden is related to the excess cognitive impairment present in older adults with",,"Rej, S.;Butters, M. A.;Aizenstein, H. J.;Begley, A.;Tsay, J.;Reynolds, C. F.;Mulsant, B. H.;Gildengers, A.",2014,April,,0,
1723,"Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites","BACKGROUND: The validity of a self-reported stroke remains inconclusive. OBJECTIVE: To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard. DESIGN, SETTING, AND PARTICIPANTS: Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan. METHODS: High-resolution quantitative MRIs were acquired for 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the chi(2) test. Putative relationships between factors potentially influencing the reporting of stroke, including memory performance, cognitive function, and vascular risk factors, were assessed using logistic regression models. Subsequently, all analyses were repeated, stratified by age, sex, ethnic group, and level of education. RESULTS: In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%. In analyses stratified by median age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity and specificity, 36.7% and 81.3% vs 27.6% and 26.2%; P = .02). Impaired memory, cognitive skills, or language ability and the presence of hypertension or myocardial infarction were associated with higher rates of false-negative results. CONCLUSIONS: Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease, and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.","African Americans/ethnology;Aged;Aged, 80 and over;Cohort Studies;Ethnic Groups;European Continental Ancestry Group/ethnology;Female;Geriatric Assessment;Hispanic Americans/ethnology;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Neurologic Examination;Neuropsychological Tests;Residence Characteristics;Self Concept;Sensitivity and Specificity;Stroke/ diagnosis/ ethnology/psychology;Surveys and Questionnaires","Reitz, C.;Schupf, N.;Luchsinger, J. A.;Brickman, A. M.;Manly, J. J.;Andrews, H.;Tang, M. X.;DeCarli, C.;Brown, T. R.;Mayeux, R.",2009,Jul,10.1001/archneurol.2009.83,0,
1724,Relation of Dysglycemia to Structural Brain Changes in a Multiethnic Elderly Cohort,"Objectives: Abnormally high glucose levels (dysglycemia) increase with age. Epidemiological studies suggest that dysglycemia is a risk factor for cognitive impairment but the underlying pathophysiological mechanisms remain unclear. The objective of this study was to examine the relation of dysglycemia clinical categories (normal glucose tolerance (NGT), pre-diabetes, undiagnosed diabetes, known diabetes) with brain structure in older adults. We also assessed the relation between dysglycemia and cognitive performance. Design: Cross-sectional and longitudinal cohort study. Setting: Northern Manhattan (Washington Heights, Hamilton Heights, and Inwood). Participants: Medicare recipients 65 years and older. Measurements: Dysglycemia categories were based on HBA1c or history of type 2 diabetes (diabetes). Brain structure (brain infarcts, white matter hyperintensities (WMH) volume, total gray matter volume, total white matter volume, total hippocampus volume) was assessed with brain magnetic resonance imaging; cognitive function (memory, language and visuospatial function, speed) was assessed with a validated neuropsychological battery. Results: Dysglycemia, defined with HbA1c as a continuous variable or categorically as pre-diabetes and diabetes, was associated with a higher number of brain infarcts, WMH volume and decreased total white matter, gray matter and hippocampus volumes cross-sectionally, and a significant decline in gray matter volume longitudinally. Dysglycemia was also associated with lower performance in language, speed and visuospatial function although these associations were attenuated when adjusted for education, APOE-ε4, ethnic group and vascular risk factors. Conclusion: Our results suggest that dysglycemia affects brain structure and cognition even in elderly survivors, evidenced by higher cerebrovascular disease, lower white and gray matter volume, and worse language and visuospatial function and cognitive speed.",hemoglobin A1c;aged;aging;analysis of variance;article;brain infarction;brain size;cognition;cognitive defect;controlled study;cross-sectional study;diabetes mellitus;dysglycemia;female;follow up;glucose tolerance;gray matter;hippocampus;human;language;major clinical study;male;medicare;memory;neuroimaging;neuropsychological test;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;risk factor;very elderly;white matter,"Reitz, C.;Guzman, V. A.;Narkhede, A.;DeCarli, C.;Brickman, A. M.;Luchsinger, J. A.",2017,,10.1111/jgs.14551,0,
1725,[Degenerative cerebellar diseases and differential diagnoses] Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen,"CLINICAL/METHODICAL ISSUE: Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. STANDARD RADIOLOGICAL METHODS: In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. ACHIEVEMENTS: In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. PRACTICAL RECOMMENDATIONS: Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions.",Ataxia;Cerebellar atrophy;Magnetic resonance imaging;Neurodegenerative diseases;Parkinson's disease,"Reith, W.;Roumia, S.;Dietrich, P.",2016,Nov,,0,
1726,Five-Year Longitudinal Brain Volume Change in Healthy Elders at Genetic Risk for Alzheimer's Disease,"Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) varepsilon4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in varepsilon4 carriers (varepsilon4+) compared to varepsilon4 non-carriers (varepsilon4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy varepsilon4+ and varepsilon4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 varepsilon4+ and 30 varepsilon4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the varepsilon4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the varepsilon4- group. Greater loss in grey matter volumes in varepsilon4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.",Alzheimer's disease;ApoE4;MRI scans;longitudinal studies,"Reiter, K.;Nielson, K. A.;Durgerian, S.;Woodard, J. L.;Smith, J. C.;Seidenberg, M.;Kelly, D. A.;Rao, S. M.",2017,,,0,
1727,Neuroanatomy of Rett syndrome: a volumetric imaging study,"Rett syndrome is a pediatric neurological disorder of unknown etiology defined by the presence of severe neurodevelopment decline, acquired microcephaly, dementia, abnormalities of movement, autistic behavior, and seizures in young female children. In this study, the neuroanatomy of 11 females with Rett syndrome and 15 age- and gender-matched control subjects was investigated in vivo with quantitative neuroimaging techniques. Compared to control subjects, the patients with Rett syndrome were found to have significantly reduced cerebral volume; evidence of greater loss of gray matter in comparison to white matter; regional variation in cortical gray matter, with the frontal regions showing the largest decrease; and reduced volume of the caudate nucleus and midbrain, even when taking into account general reduction in the size of the brain. In addition, there was no evidence of an ongoing degenerative process in this sample of girls with Rett syndrome. The consistency of these data with results from neuropathological investigations points to the need for continued quantitative neuroimaging studies of children with this condition. In particular, research employing serial longitudinal scans of very young children manifesting early signs of the clinical syndrome holds promise for helping to elucidate the neuropathological pathways leading to the debilitating clinical manifestations of Rett syndrome.","Adolescent;Adult;Brain/anatomy & histology/ pathology;Case-Control Studies;Caudate Nucleus/anatomy & histology/pathology;Child;Child, Preschool;Female;Humans;Magnetic Resonance Imaging;Rett Syndrome/cerebrospinal fluid/ pathology","Reiss, A. L.;Faruque, F.;Naidu, S.;Abrams, M.;Beaty, T.;Bryan, R. N.;Moser, H.",1993,Aug,10.1002/ana.410340220,0,
1728,The investigation of dementia syndromes by 133Xenon dynamic single photon emission computed tomography,The patterns of regional cerebral blood flow (rCBF) in patients with dementia caused by Alzheimer's disease is compared with that of patients with dementia caused by multiple cerebral infarctions. A total of 47 patients were examined with 133Xenon SPECT. The results show that the global CBF correlates with the severity of dementia caused by Alzheimer's disease and that the two forms of dementia show two different patterns of disturbances.,"Aged;Aged, 80 and over;Alzheimer Disease/radionuclide imaging;Brain/physiopathology/*radionuclide imaging;Dementia/*radionuclide imaging;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Syndrome;*Tomography, Emission-Computed;*Xenon","Reischies, F. M.;Hedde, J. P.;Gutzmann, H.",1987,,,0,
1729,Skin biopsy findings and results of neuropsychological testing in the first confirmed cases of CADASIL in Norway,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by mutations in the notch3 gene. The mutation can be demonstrated by a gene test. The first group of Norwegian patients with CADASIL confirmed by gene testing was recently described. The present study includes six of the original nine patients with demonstrated notch3 mutation plus one patient with symptoms, who had been unwilling to go through gene testing. These seven patients underwent skin biopsy for electron microscopy. One patient was cognitively too impaired, but six went through neuropsychological testing. By electron microscopy characteristic granular osmiophilic material (GOM) was detected in all skin biopsies. The material is seen as granular deposits in the basal lamina of the smooth muscle layer, often making impressions upon adjacent smooth muscle cells. It seems important that blood vessels over a certain size (diameter >20 microm) are examined. A varying extent of cognitive decline was noted amongst all by neuropsychological testing. In cases with multiple infarctions reduction of perceptual speed, visuospatial skills and working memory could be demonstrated. Four patients showed executive dysfunction.","Adult;Aged;Arterioles/ultrastructure;Biopsy;Brain/pathology;CADASIL/*diagnosis/*physiopathology;Cognition Disorders/etiology/physiopathology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Microscopy, Electron, Transmission;Middle Aged;Multiple Sclerosis/pathology;*Neuropsychological Tests;Norway;Sensitivity and Specificity;Skin/blood supply/*ultrastructure","Rein Gustavsen, W.;Reinholt, F. P.;Schlosser, A.",2006,Apr,10.1111/j.1468-1331.2006.01243.x,0,
1730,Accelerated cognitive decline in patients with type 2 diabetes: MRI correlates and risk factors,"BACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of cognitive decline and dementia. We examined brain imaging correlates and vascular and metabolic risk factors of accelerated cognitive decline in patients with type 2 diabetes. METHODS: Cognitive functioning and brain volume as well as metabolic and vascular risk factors were assessed twice in 68 patients with no dementia with type 2 diabetes with a 4-year interval. Thirty-eight control participants served as a reference group. Volumetric measurements of the total brain, lateral ventricles and white-matter hyperintensities were performed on 1.5T magnetic resonance imaging scans. A regression-based index score was calculated on the basis of the reference group to assess changes in cognitive performance over time, adjusted for age, sex and estimated intelligence quotient. Brain volumes were compared between patients with and without accelerated cognitive decline. Logistic regression analyses were used to identify baseline risk factors for accelerated cognitive decline within the diabetes group. RESULTS: Accelerated cognitive decline was found in 17 (25%) patients with type 2 diabetes and was associated with a greater increase in ventricular volume [mean difference (95% confidence interval): 0.23% (0.08-0.38); p = 0.003] and white-matter hyperintensities volume [0.16% (0.05-0.27); p = 0.006] over the 4-year period. There were no specific vascular or metabolic risk factors associated with accelerated cognitive decline. CONCLUSIONS: Accelerated cognitive decline in patients with type 2 diabetes was associated with progressive changes on brain magnetic resonance imaging, comprising both vascular damage and global atrophy. Exploration of vascular and metabolic risk factors revealed no specific determinants of accelerated cognitive decline.","Aged;Aged, 80 and over;Brain/metabolism/ pathology;Brain Mapping;Case-Control Studies;Cognition Disorders/ etiology/physiopathology;Dementia/etiology/pathology;Diabetes Complications;Diabetes Mellitus, Type 2/ complications/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Vascular Diseases/ etiology/pathology","Reijmer, Y. D.;van den Berg, E.;de Bresser, J.;Kessels, R. P.;Kappelle, L. J.;Algra, A.;Biessels, G. J.",2011,Feb,10.1002/dmrr.1163,0,
1731,Improved sensitivity to cerebral white matter abnormalities in Alzheimer's disease with spherical deconvolution based tractography,"Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with ""crossing fibers."" Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of ""crossing fibers"" on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer's disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of ""crossing fibers,"" i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with ""crossing fibers"" the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture.","Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Cerebrum/ abnormalities/ pathology/physiopathology;Cognition;Corpus Callosum/pathology/physiopathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Memory;Nerve Fibers, Myelinated/pathology","Reijmer, Y. D.;Leemans, A.;Heringa, S. M.;Wielaard, I.;Jeurissen, B.;Koek, H. L.;Biessels, G. J.",2012,,10.1371/journal.pone.0044074,0,
1732,Disruption of cerebral networks and cognitive impairment in Alzheimer disease,"OBJECTIVE: To examine the relation between measures of whole-brain white matter connectivity and cognitive performance in patients with early Alzheimer disease (AD) using a network-based approach and to assess whether network parameters provide information that is complementary to conventional MRI markers of AD. METHODS: Fifty patients (mean age 78.8 +/- 7.1 years) with early AD were recruited via a memory clinic. In addition, 15 age-, sex-, and education-matched control participants were used as a reference group. All participants underwent a 3-T MRI scan and cognitive assessment. Diffusion tensor imaging-based tractography was used to reconstruct the brain network of each individual, followed by graph theoretical analyses. Overall network efficiency was assessed by measures of local (clustering coefficient, local efficiency) and global (path length, global efficiency) connectivity. Age-, sex-, and education-adjusted cognitive scores were related to network measures and to conventional MRI parameters (i.e., degree of cerebral atrophy and small-vessel disease). RESULTS: The structural brain network of patients showed reduced local efficiency compared to controls. Within the patient group, worse performance in memory and executive functioning was related to decreased local efficiency (r = 0.434; p = 0.002), increased path length (r = -0.538; p < 0.001), and decreased global efficiency (r = 0.431; p = 0.005). Measures of network efficiency explained up to 27% of the variance in cognitive functioning on top of conventional MRI markers (p < 0.01). CONCLUSION: This study shows that network-based analysis of brain white matter connections provides a novel way to reveal the structural basis of cognitive dysfunction in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/ pathology;Atrophy;Case-Control Studies;Cerebral Cortex/ pathology;Cognition Disorders/ etiology;Executive Function/physiology;Female;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Memory Disorders/etiology;Nerve Fibers, Myelinated/pathology;Neural Pathways/ pathology/physiology;Neuropsychological Tests;Statistics as Topic","Reijmer, Y. D.;Leemans, A.;Caeyenberghs, K.;Heringa, S. M.;Koek, H. L.;Biessels, G. J.",2013,Apr 9,10.1212/WNL.0b013e31828c2ee5,0,
1733,Structural network alterations and neurological dysfunction in cerebral amyloid angiopathy,"Cerebral amyloid angiopathy is a common form of small-vessel disease and an important risk factor for cognitive impairment. The mechanisms linking small-vessel disease to cognitive impairment are not well understood. We hypothesized that in patients with cerebral amyloid angiopathy, multiple small spatially distributed lesions affect cognition through disruption of brain connectivity. We therefore compared the structural brain network in patients with cerebral amyloid angiopathy to healthy control subjects and examined the relationship between markers of cerebral amyloid angiopathy-related brain injury, network efficiency, and potential clinical consequences. Structural brain networks were reconstructed from diffusion-weighted magnetic resonance imaging in 38 non-demented patients with probable cerebral amyloid angiopathy (69 ± 10 years) and 29 similar aged control participants. The efficiency of the brain network was characterized using graph theory and brain amyloid deposition was quantified by Pittsburgh compound B retention on positron emission tomography imaging. Global efficiency of the brain network was reduced in patients compared to controls (0.187 ± 0.018 and 0.201 ± 0.015, respectively, P < 0.001). Network disturbances were most pronounced in the occipital, parietal, and posterior temporal lobes. Among patients, lower global network efficiency was related to higher cortical amyloid load (r = -0.52; P = 0.004), and to magnetic resonance imaging markers of small-vessel disease including increased white matter hyperintensity volume (P < 0.001), lower total brain volume (P = 0.02), and number of microbleeds (trend P = 0.06). Lower global network efficiency was also related to worse performance on tests of processing speed (r = 0.58, P < 0.001), executive functioning (r = 0.54, P = 0.001), gait velocity (r = 0.41, P = 0.02), but not memory. Correlations with cognition were independent of age, sex, education level, and other magnetic resonance imaging markers of small-vessel disease. These findings suggest that reduced structural brain network efficiency might mediate the relationship between advanced cerebral amyloid angiopathy and neurologic dysfunction and that such large-scale brain network measures may represent useful outcome markers for tracking disease progression.",Pittsburgh compound B;aged;article;brain;brain injury;brain size;clinical article;cohort analysis;controlled study;cross-sectional study;diffusion weighted imaging;executive function;female;gait;human;human tissue;longitudinal study;male;neuroimaging;neurologic disease;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;positron emission tomography;priority journal;quantitative analysis;temporal lobe;vascular amyloidosis;white matter,"Reijmer, Y. D.;Fotiadis, P.;Martinez-Ramirez, S.;Salat, D. H.;Schultz, A.;Shoamanesh, A.;Ayres, A. M.;Vashkevich, A.;Rosas, D.;Schwab, K.;Leemans, A.;Biessels, G. J.;Rosand, J.;Johnson, K. A.;Viswanathan, A.;Gurol, M. E.;Greenberg, S. M.",2015,,,0,
1734,Patterns of cortical degeneration in an elderly cohort with cerebral small vessel disease,"Emerging noninvasive neuroimaging techniques allow for the morphometric analysis of patterns of gray and white matter degeneration in vivo, which may help explain and predict the occurrence of cognitive impairment and Alzheimer's disease. A single center prospective follow-up study (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study (RUN DMC)) was performed involving 503 nondemented elderly individuals (50-85 years) with a history of symptomatic cerebral small vessel disease (SVD). Age was associated with a global reduction in cortical thickness, and this relationship was strongest for ventrolateral prefrontal cortex, auditory cortex, Wernicke's area, superior temporal lobe, and primary visual cortex. Right and left hemispheres differed in the thickness of language-related areas. White matter (WM) lesions were generally negatively correlated with cortical thickness, primarily in individuals over the age of 60, with the notable exception of Brodmann areas 4 and 5, which were positively correlated in age groups 50-60 and 60-70, respectively. The observed pattern of age-related decline may explain problems in memory and executive functions, which are already well documented in individuals with SVD. The additional gray matter loss affecting visual and auditory cortex, and specifically the head region of primary motor cortex, may indicate morphological correlates of impaired sensory and motor functions. The paradoxical positive relationship between WM lesion volume and cortical thickness in some areas may reflect early compensatory hypertrophy. This study raises a further interest in the mechanisms underlying cerebral gray and white matter degeneration in association with SVD, which will require further investigation with diffusion weighted and longitudinal MR studies.","Aged;Aged, 80 and over;Aging/ pathology;Atrophy/etiology/ pathology/physiopathology;Cerebral Cortex/blood supply/ pathology/physiopathology;Cerebrovascular Disorders/ pathology/physiopathology;Cohort Studies;Female;Humans;Male;Middle Aged;Nerve Degeneration/etiology/ pathology/physiopathology;Prospective Studies","Reid, A. T.;van Norden, A. G.;de Laat, K. F.;van Oudheusden, L. J.;Zwiers, M. P.;Evans, A. C.;de Leeuw, F. E.;Kotter, R.",2010,Dec,10.1002/hbm.20994,0,
1735,Diagnosis of multi-infarct dementia: predictive value of clinical criteria,Clinical and neuroimaging features that best discriminated a multi-infarct dementia diagnosis from a diagnosis of Alzheimer's disease were retrospectively reviewed for 192 patients of a university-based dementia diagnostic clinic. Only a subset of features usually ascribed to multi-infarct dementia actually distinguished that diagnosis from the diagnosis of Alzheimer's disease.,"Aged;Alzheimer Disease/*diagnosis/psychology;Brain/pathology;Dementia, Multi-Infarct/*diagnosis/psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Tomography, X-Ray Computed","Reichman, W. E.;Coyne, A. C.;Shah, A.",1993,Jun,10.2466/pms.1993.76.3.793,0,
1736,Cognitive Function and 3-Tesla Magnetic Resonance Imaging Tractography of White Matter Hyperintensities in Elderly Persons,"BACKGROUND/AIMS: This study used 3-Tesla magnetic resonance imaging (MRI) tractography to determine if there was an association between tracts crossing white matter hyperintensities (WMH) and cognitive function in elderly persons. METHODS: Brain T2-weighted fluid-attenuated inversion recovery (FLAIR) and diffusion tensor MRI scans were acquired in participants above the age of 60 years. Twenty-six persons had WMH identified on T2 FLAIR scans. They completed a battery of neuropsychological tests and were classified as normal controls (n = 15) or with Alzheimer's dementia (n = 11). Tractography was generated by the Fiber Assignment by Continuous Tracking method. All tracts that crossed WMH were segmented. The average fractional anisotropy and average mean diffusivity of these tracts were quantified. We studied the association between cognitive test scores with the average mean diffusivity and average fractional anisotropy of tracts while controlling for age, total WMH volume and diagnosis. RESULTS: An increased mean diffusivity of tracts crossing WMH was associated with worse performance on the Wechsler Memory Scale-III Longest Span Forward (p = 0.02). There was no association between the fractional anisotropy of tracts and performance on cognitive testing. CONCLUSION: The mean diffusivity of tracts crossing WMH measured by tractography is a novel correlate of performance on the Wechsler Memory Scale-III Longest Span Forward in elderly persons.",,"Reginold, W.;Luedke, A. C.;Tam, A.;Itorralba, J.;Fernandez-Ruiz, J.;Reginold, J.;Islam, O.;Garcia, A.",2015,Sep-Dec,10.1159/000439045,0,
1737,Altered Superficial White Matter on Tractography MRI in Alzheimer's Disease,"BACKGROUND/AIMS: Superficial white matter provides extensive cortico-cortical connections. This tractography study aimed to assess the diffusion characteristics of superficial white matter tracts in Alzheimer's disease. METHODS: Diffusion tensor 3T magnetic resonance imaging scans were acquired in 24 controls and 16 participants with Alzheimer's disease. Neuropsychological test scores were available in some participants. Tractography was performed by the Fiber Assignment by Continuous Tracking (FACT) method. The superficial white matter was manually segmented and divided into frontal, parietal, temporal and occipital lobes. The mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AxD) and fractional anisotropy (FA) of these tracts were compared between controls and participants with Alzheimer's disease and correlated with available cognitive tests while adjusting for age and white matter hyperintensity volume. RESULTS: Alzheimer's disease was associated with increased MD (p = 0.0011), increased RD (p = 0.0019) and increased AxD (p = 0.0017) in temporal superficial white matter. In controls, superficial white matter was associated with the performance on the Montreal Cognitive Assessment, Stroop and Trail Making Test B tests, whereas in Alzheimer's disease patients, it was not associated with the performance on cognitive tests. CONCLUSION: Temporal lobe superficial white matter appears to be disrupted in Alzheimer's disease.",Cognitive function;Diffusion tensor imaging;Tractography,"Reginold, W.;Luedke, A. C.;Itorralba, J.;Fernandez-Ruiz, J.;Islam, O.;Garcia, A.",2016,May-Aug,10.1159/000446770,0,
1738,Correlating quantitative tractography at 3T MRI and cognitive tests in healthy older adults,"This study used diffusion tensor imaging tractography at 3 T MRI to relate cognitive function to white matter tracts in the brain. Brain T2 fluid attenuated inversion recovery-weighted and diffusion tensor 3 T MRI scans were acquired in thirty-three healthy participants without mild cognitive impairment or dementia. They completed a battery of neuropsychological tests including the Montreal Cognitive Assessment, Stroop test, Trail Making Test B, Wechsler Memory Scale-III Longest span forward, Wechsler Memory Scale-III Longest span backward, Mattis Dementia Rating Scale, California Verbal Learning Test Version II Long Delay Free Recall, and Letter Number Sequencing. Tractography was generated by the Fiber Assignment by Continuous Tracking method. The corpus callosum, cingulum, long association fibers, corticospinal/bulbar tracts, thalamic projection fibers, superior cerebellar peduncle, middle cerebellar peduncle and inferior cerebellar peduncle were manually segmented. The fractional anisotropy (FA) and mean diffusivity (MD) of these tracts were quantified. We studied the association between cognitive test scores and the MD and FA of tracts while controlling for age and total white matter hyperintensities volume. Worse scores on the Stroop test was associated with decreased FA of the corpus callosum, corticospinal/bulbar tract, and thalamic projection tracts. Scores on the other cognitive tests were not associated with either the FA or MD of measured tracts. In healthy persons the Stroop test appears to be a better predictor of the microstructural integrity of white matter tracts measured by DTI tractography than other cognitive tests.",adult;article;assessment of humans;brain size;California verbal learning test;cingulum (brain);cognition;controlled study;corpus callosum;diffusion tensor imaging;female;fractional anisotropy;human;human experiment;inferior cerebellar peduncle;male;Mattis Dementia Rating Scale;middle aged;middle cerebellar peduncle;Montreal cognitive assessment;neuropsychological test;normal human;nuclear magnetic resonance imaging;priority journal;pyramidal tract;Stroop test;superior cerebellar peduncle;thalamus;trail making test;Wechsler memory scale;3 Tesla Siemens Magnetom Trio MRI,"Reginold, W.;Itorralba, J.;Tam, A.;Luedke, A. C.;Fernandez-Ruiz, J.;Reginold, J.;Islam, O.;Garcia, A.",2016,,10.1007/s11682-015-9495-0,0,1739
1739,Correlating quantitative tractography at 3T MRI and cognitive tests in healthy older adults,"This study used diffusion tensor imaging tractography at 3 T MRI to relate cognitive function to white matter tracts in the brain. Brain T2 fluid attenuated inversion recovery-weighted and diffusion tensor 3 T MRI scans were acquired in thirty-three healthy participants without mild cognitive impairment or dementia. They completed a battery of neuropsychological tests including the Montreal Cognitive Assessment, Stroop test, Trail Making Test B, Wechsler Memory Scale-III Longest span forward, Wechsler Memory Scale-III Longest span backward, Mattis Dementia Rating Scale, California Verbal Learning Test Version II Long Delay Free Recall, and Letter Number Sequencing. Tractography was generated by the Fiber Assignment by Continuous Tracking method. The corpus callosum, cingulum, long association fibers, corticospinal/bulbar tracts, thalamic projection fibers, superior cerebellar peduncle, middle cerebellar peduncle and inferior cerebellar peduncle were manually segmented. The fractional anisotropy (FA) and mean diffusivity (MD) of these tracts were quantified. We studied the association between cognitive test scores and the MD and FA of tracts while controlling for age and total white matter hyperintensities volume. Worse scores on the Stroop test was associated with decreased FA of the corpus callosum, corticospinal/bulbar tract, and thalamic projection tracts. Scores on the other cognitive tests were not associated with either the FA or MD of measured tracts. In healthy persons the Stroop test appears to be a better predictor of the microstructural integrity of white matter tracts measured by DTI tractography than other cognitive tests.",,"Reginold, W.;Itorralba, J.;Tam, A.;Luedke, A. C.;Fernandez-Ruiz, J.;Reginold, J.;Islam, O.;Garcia, A.",2015,Dec 9,10.1007/s11682-015-9495-0,0,
1740,Cerebellar abnormalities in Huntington's disease: a role in motor and psychiatric impairment?,"The cerebellum has received limited attention in Huntington's disease (HD), despite signs of possible cerebellar dysfunction, including motor incoordination and impaired gait, which are currently attributed to basal ganglia atrophy and disrupted fronto-striatal circuits. This study is the first to investigate a potential contribution of macro- and microstructural cerebellar damage to clinical manifestations of HD. T1- and diffusion-weighted 3T magnetic resonance imaging (MRI) scans were obtained from 12 controls and 22 early-stage HD participants. Manual delineation and voxel-based morphometry were used to assess between-group differences in cerebellar volume, and diffusion metrics were compared between groups within the cerebellar gray and white matter. Associations between these imaging measures and clinical scores were examined within the HD group. Reduced paravermal volume was detected in HD compared with controls using voxel-based morphometry (P < 0.05), but no significant volumetric differences were found using manual delineation. Diffusion abnormalities were detected in both cerebellar gray matter and white matter. Smaller cerebellar volumes, although not significantly reduced, were significantly associated with impaired gait and psychiatric morbidity and of borderline significance with pronate/supinate-hand task performance. Abnormal cerebellar diffusion was associated with increased total motor score, impaired saccade initiation, tandem walking, and timed finger tapping. In conclusion, atrophy of the paravermis, possibly encompassing the cerebellar nuclei, and microstructural abnormalities within the cerebellum may contribute to HD neuropathology. Aberrant cerebellar diffusion and reduced cerebellar volume together associate with impaired motor function and increased psychiatric symptoms in stage I HD, potentially implicating the cerebellum more centrally in HD presentation than previously recognized.","Adult;Aged;Atrophy;Brain Mapping;Cerebellar Diseases/complications/ etiology;Cerebellum/ pathology;Disability Evaluation;Female;Humans;Huntington Disease/ complications/ pathology;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Mental Disorders/ etiology;Middle Aged;Movement Disorders/ etiology;Psychiatric Status Rating Scales;Young Adult","Rees, E. M.;Farmer, R.;Cole, J. H.;Haider, S.;Durr, A.;Landwehrmeyer, B.;Scahill, R. I.;Tabrizi, S. J.;Hobbs, N. Z.",2014,Nov,10.1002/mds.25984,0,
1741,Alzheimer's disease and vascular deficiency: lessons from imaging studies and down syndrome,"Down syndrome (DS) individuals are at high risk for developing Alzheimer's disease (AD) and consequently provide a unique opportunity to examine the factors leading to the onset of AD. This paper focuses on the neglected vascular parallels between AD and DS that can readily be examined in DS. Several recent AD studies provide evidence that internal jugular vein (IJV) reflux may result in white matter lesions and a 30% decrease in cerebrospinal fluid (CSF) clearance of amyloid-beta. At the same time, studies analyzing the synthesis of amyloid-beta in DS showed greater than expected amounts of Abeta than would be predicted by the increase in gene dosage, perhaps due to slower clearance. These studies are discussed along with the possibility that the venous and CSF dysfunction found in AD patients may be present early in life in persons with DS, leaving them particularly vulnerable to early onset AD. Studying IJV function in DS provides an opportunity to understand the role of vascular function in the initiation of AD.",,"Reed-Cossairt, A.;Zhu, X.;Lee, H. G.;Reed, C.;Perry, G.;Petersen, R. B.",2012,,10.1155/2012/929734,0,
1742,Effects of white matter lesions and lacunes on cortical function,"BACKGROUND: Subcortical ischemic vascular dementia has been ascribed to prominent frontal lobe dysfunction secondary to ischemic lesions in frontothalamic circuits. Whether small-vessel disease in fact predominantly affects the frontal lobes is not well documented. OBJECTIVE: To investigate the effects of subcortical lesions (lacunes and white matter lesions [WML]) on cortical function, as reflected in glucose metabolism and cognitive function, in elderly individuals. DESIGN: Cross-sectional analyses of case series. SETTING: Multicenter, university-based study of subcortical vascular dementia. PATIENTS: Persons with normal cognition, mild cognitive impairment, or dementia and with and without lacunes on magnetic resonance images. MAIN OUTCOME MEASURES: Regional cerebral glucose metabolism, normalized regional metabolic activity, and neuropsychological test scores. Major hypotheses were that volume of lacunes and WML correlate selectively with hypometabolism of prefrontal cortex and failure of executive cognitive ability. RESULTS: Lacunes correlated with metabolic rates in dorsolateral frontal cortex (DLF); WML substantially reduced metabolic rates throughout cortex, most strongly so in DLF. When regional metabolic activity was normalized to whole brain activity, lacunes remained correlated with DLF activity, whereas the WML effect was no longer found, probably because of its general distribution. Regional cerebral glucose metabolism and normalized activity in DLF also correlated with cortical atrophy. Metabolic activity in DLF correlated with executive function, memory, and global cognitive function, while activity in middle temporal gyrus correlated with memory and global function but not executive function. CONCLUSIONS: The metabolic effects of lacunes and WML are most apparent in DLF, but the effects of WML are generalized and frontal hypometabolism correlates with memory and global impairment, cognitive as well as executive function. The effects of subcortical cerebrovascular disease appear to converge on the frontal lobes but are diffuse, complex, and of modest magnitude.","Aged;Aged, 80 and over;Brain Infarction/metabolism/pathology/ physiopathology;Brain Mapping;Cerebral Cortex/ physiology;Cognition Disorders/metabolism/pathology/ physiopathology;Cross-Sectional Studies;Dementia, Vascular/metabolism/pathology/ physiopathology;Energy Metabolism/physiology;Female;Glucose/metabolism;Humans;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests/statistics & numerical data;Positron-Emission Tomography/methods;Problem Solving/physiology;Statistics as Topic","Reed, B. R.;Eberling, J. L.;Mungas, D.;Weiner, M.;Kramer, J. H.;Jagust, W. J.",2004,Oct,10.1001/archneur.61.10.1545,0,
1743,Frontal lobe hypometabolism predicts cognitive decline in patients with lacunar infarcts,"Background: A proportion of patients with subcortical lacunes will suffer progressive cognitive dysfunction, but the basis for this decline is controversial and little is known about predicting cognitive decline in these patients. Studies of Alzheimer disease have shown that imaging measures of temporal and parietal metabolism and blood flow predict disease course. Objective: To determine whether regional cerebral glucose metabolism predicts cognitive decline by testing 2 opposing hypotheses: (1) temporoparietal activity predicts decline (based on the idea that concomitant Alzheimer disease causes decline) vs (2) frontal hypometabolism predicts decline (based on evidence that subcortical frontal circuits are especially vulnerable to small vessel ischemia). Design: Prospective cohort study. Setting: University outpatient dementia center. Patients: A convenience sample of 26 patients with radiologically defined lacunes and baseline cognitive function ranging from normal to moderately demented. Main Outcome Measures: Regional cerebral metabolism was quantitated in the form of atrophy-corrected positron emission tomographic activity ratios in cortical regions that were defined a priori. Patients were followed up at a mean of 1.8 years, and the dependent variable was rate of change in the Mini-Mental State Examination score. Results: Bilateral and right hemisphere dorsolateral frontal metabolism significantly predicted cognitive decline, with right dorsolateral frontal metabolism explaining 19% of the variance. No other positron emission tomographic region was a significant predictor, nor were demographic variables or baseline Mini-Mental State Examination scores significant predictors. Conclusion: Cognitive decline in patients with lacunes may result in part from progressive vascular compromise in subcortical frontal circuits.",,"Reed, B. R.;Eberling, J. L.;Mungas, D.;Weiner, M.;Jagust, W. J.",2001,2001,,0,
1744,Functional reorganization of motor cortex increases with greater axonal injury from CADASIL,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease that clinically involves only the brain. Particularly early in the disease, patients can show substantial or complete recovery after individual strokes. Cortical functional reorganization may contribute to limiting disability with such ischemic injury. We sought to test whether the extent of any functional changes in the motor cortex increases with greater brain axonal injury from CADASIL. METHODS: Functional MRI (fMRI) was used to characterize cortical activation during a simple hand-tapping task. Disease-associated pathology in subcortical white matter was assessed with the use of conventional fluid-attenuated inversion recovery (FLAIR) MRI and MR spectroscopic imaging for measurement of N-acetyl aspartate decreases, a relatively specific measure of axonal injury. RESULTS: There was evidence for variable but substantial hyperintense white matter signal in all of the patients with FLAIR imaging. With the use of fMRI, the brain regions activated during motor tasks were similar for the 9 CADASIL patients and 7 controls, except that most (6 of 9) patients showed primary motor cortex activation both ipsilateral and contralateral to the hand moved, a finding in only 1 of 7 healthy controls. Ipsilateral motor cortex activation increased (r=-0.77, P<0.05) and motor cortex activation lateralization index decreased (r=0.68, P<0.02) with greater white matter injury (as assessed from decreases in the relative N-acetyl aspartate concentration) in a region of interest including descending motor fibers of the corticospinal pathway. CONCLUSIONS: The extent of functional reorganization of motor cortex increases with increasing axonal injury, consistent with an adaptive role for these changes. Increased functional recruitment of cortex ipsilateral to the limb moved therefore may contribute to limiting motor impairment from the subcortical injury of CADASIL.","Adaptation, Physiological;Adult;Aspartic Acid/ analogs & derivatives/metabolism;Axons/pathology;Creatine/metabolism;Dementia, Multi-Infarct/diagnosis/pathology/ physiopathology;Female;Hand;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Motor Activity;Motor Cortex/blood supply/pathology/ physiopathology;Severity of Illness Index","Reddy, H.;De Stefano, N.;Mortilla, M.;Federico, A.;Matthews, P. M.",2002,Feb,,0,
1745,"Apolipoprotein E-e4, processing speed, and white matter volume in a genetically enriched sample of midlife adults","Healthy midlife children of a parent with Alzheimer's disease ([AD] N = 23; 9 male) participated in neuropsychological testing, and magnetic resonance imaging (MRI) of brain volumetrics were obtained. In all, 35% of the sample were apolipoprotein E (ApoE)-e4 positive (n = 8; 5 male). The ApoE-e4 group exhibited significantly slower performances on an executive function and processing speed measure and had less white matter volume than the non-ApoE-e4 group. Lesser white matter volume was significantly correlated with slower processing speed. Processing speed and changes in white matter volume might be indicators of preclinical decline in AD. © 2011 The Author(s).",,"Ready, R. E.;Baran, B.;Chaudhry, M.;Schatz, K.;Gordon, J.;Spencer, R. M. C.",2011,September,,0,
1746,Regional white matter change in pre-symptomatic Huntington's disease: a diffusion tensor imaging study,"The pathology of Huntington's disease (HD) is characterized by diffuse brain atrophy, with the most substantial neuronal loss occurring in the caudate and putamen. Recent evidence suggests that there may be more widespread neuronal degeneration with significant involvement of extrastriate structures, including white matter. In this study of pre-symptomatic carriers of the HD genetic mutation, we have used diffusion tensor imaging to examine the integrity and organization of white matter in a group of individuals who previously demonstrated abnormalities in response to a functional magnetic resonance imaging paradigm. Our results indicate that, before the onset of manifest HD, there are regional decreases in fractional anisotropy, indicating early white matter disorganization.",Adult;Anisotropy;Atrophy/pathology;Brain/ pathology;Caudate Nucleus/pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Huntington Disease/ pathology;Male;Nerve Degeneration/pathology;Putamen/pathology,"Reading, S. A.;Yassa, M. A.;Bakker, A.;Dziorny, A. C.;Gourley, L. M.;Yallapragada, V.;Rosenblatt, A.;Margolis, R. L.;Aylward, E. H.;Brandt, J.;Mori, S.;van Zijl, P.;Bassett, S. S.;Ross, C. A.",2005,Oct 30,10.1016/j.pscychresns.2005.05.011,0,
1747,Principal component analysis with pre-normalization improves the signal-to-noise ratio and image quality in positron emission tomography studies of amyloid deposits in Alzheimer's disease,"This study introduces a new approach for the application of principal component analysis (PCA) with pre-normalization on dynamic positron emission tomography (PET) images. These images are generated using the amyloid imaging agent N-methyl [(11)C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole ([(11)C]PIB) in patients with Alzheimer's disease (AD) and healthy volunteers (HVs). The aim was to introduce a method which, by using the whole dataset and without assuming a specific kinetic model, could generate images with improved signal-to-noise and detect, extract and illustrate changes in kinetic behavior between different regions in the brain. Eight AD patients and eight HVs from a previously published study with [(11)C]PIB were used. The approach includes enhancement of brain regions where the kinetics of the radiotracer are different from what is seen in the reference region, pre-normalization for differences in noise levels and removal of negative values. This is followed by slice-wise application of PCA (SW-PCA) on the dynamic PET images. Results obtained using the new approach were compared with results obtained using reference Patlak and summed images. The new approach generated images with good quality in which cortical brain regions in AD patients showed high uptake, compared to cerebellum and white matter. Cortical structures in HVs showed low uptake as expected and in good agreement with data generated using kinetic modeling. The introduced approach generated images with enhanced contrast and improved signal-to-noise ratio (SNR) and discrimination power (DP) compared to summed images and parametric images. This method is expected to be an important clinical tool in the diagnosis and differential diagnosis of dementia.","Algorithms;Alzheimer Disease/ radionuclide imaging;Amyloid beta-Peptides/ analysis;Benzothiazoles;Brain/metabolism/ radionuclide imaging;Humans;Image Enhancement/ methods;Image Processing, Computer-Assisted/methods;Kinetics;Positron-Emission Tomography/ methods;Principal Component Analysis","Razifar, P.;Engler, H.;Blomquist, G.;Ringheim, A.;Estrada, S.;Langstrom, B.;Bergstrom, M.",2009,Jun 7,10.1088/0031-9155/54/11/021,0,
1748,Parallel nonlinear analysis of weighted brain's gray and white matter images for Alzheimer's dementia diagnosis,"In this study, we are proposing a novel nonlinear classification approach to discriminate between Alzheimer's Disease (AD) and a control group using T1-weighted and T2-weighted Magnetic Resonance Images (MRI's) of brain. Since T1-weighted images and T2-weighted images have inherent physical differences, obviously each of them has its own particular medical data and hence, we extracted some specific features from each. Then the variations of the relevant eigenvalues of the extracted features were tracked to pick up the most informative ones. The final features were assigned to two parallel systems to be nonlinearly categorized. Considering the fact that AD defects the white and gray regions of brain more than its black and marginal regions, and also since T1-weighted has more medical data of white and gray regions than T2-weighted images, we put optimal weights for the two outputs. Combination of these two results made the final decision of AD diagnosis system. The dataset includes 60 T1-weighted images and 60 T2-weighted images of normal and abnormal cases. The dataset which includes different cross-sections of the brain, after an accurate registration, was split to two groups of test set (40 percent of the dataset) and training set (60 percent of the dataset). The results demonstrate more than two thirds of accuracy in detection of normal and abnormal images.",Alzheimer disease;article;brain;cell death;diagnostic imaging;factual database;human;methodology;nerve cell;nonlinear system;pathology,"Razavian, S. M.;Torabi, M.;Kim, K.",2010,,,0,1749
1749,Parallel nonlinear analysis of weighted brain's gray and white matter images for Alzheimer's dementia diagnosis,"In this study, we are proposing a novel nonlinear classification approach to discriminate between Alzheimer's Disease (AD) and a control group using T1-weighted and T2-weighted Magnetic Resonance Images (MRI's) of brain. Since T1-weighted images and T2-weighted images have inherent physical differences, obviously each of them has its own particular medical data and hence, we extracted some specific features from each. Then the variations of the relevant eigenvalues of the extracted features were tracked to pick up the most informative ones. The final features were assigned to two parallel systems to be nonlinearly categorized. Considering the fact that AD defects the white and gray regions of brain more than its black and marginal regions, and also since T1-weighted has more medical data of white and gray regions than T2-weighted images, we put optimal weights for the two outputs. Combination of these two results made the final decision of AD diagnosis system. The dataset includes 60 T1-weighted images and 60 T2-weighted images of normal and abnormal cases. The dataset which includes different cross-sections of the brain, after an accurate registration, was split to two groups of test set (40 percent of the dataset) and training set (60 percent of the dataset). The results demonstrate more than two thirds of accuracy in detection of normal and abnormal images.","Alzheimer Disease/ diagnosis/ pathology;Brain/ pathology;Cell Death;Databases, Factual;Diagnostic Imaging/ methods;Humans;Neurons/pathology;Nonlinear Dynamics","Razavian, S. M.;Torabi, M.;Kim, K.",2010,,10.1109/iembs.2010.5626791,0,
1750,Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: Evidence from MRI morphometry,"We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlational analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.",article;brain region;clinical article;cognition;correlation function;Down syndrome;human;intelligence;language;morphometry;nuclear magnetic resonance imaging;priority journal,"Raz, N.;Torres, I. J.;Briggs, S. D.;Spencer, W. D.;Thornton, A. E.;Loken, W. J.;Gunning, F. M.;McQuain, J. D.;Driesen, N. R.;Acker, J. D.",1995,,,0,1751
1751,Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry,"We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlation analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.",Analysis of Variance;Brain [abnormalities] [anatomy & histology] [pathology];Cognition;Down Syndrome [pathology] [physiopathology] [psychology];Intelligence;Intelligence Tests;Language;Magnetic Resonance Imaging;Organ Specificity;Reference Values;Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-behav,"Raz, N.;Torres, I. J.;Briggs, S. D.;Spencer, W. D.;Thornton, A. E.;Loken, W. J.;Gunning, F. M.;McQuain, J. D.;Driesen, N. R.;Acker, J. D.",1995,,,0,
1752,Cholinergic basal forebrain structure influences the reconfiguration of white matter connections to support residual memory in mild cognitive impairment,"The fornix and hippocampus are critical to recollection in the healthy human brain. Fornix degeneration is a feature of aging and Alzheimer’s disease. In the presence of fornix damage in mild cognitive impairment (MCI), a recognized prodrome of Alzheimer’s disease, recall shows greater dependence on other tracts, notably the parahippocampal cingulum (PHC). The current aims were to determine whether this shift is adaptive and to probe its relationship to cholinergic signaling, which is also compromised in Alzheimer’s disease. Twenty-five human participants with MCI and 20 matched healthy volunteers underwent diffusion MRI, behavioral assessment, and volumetric measurement of the basal forebrain. In a regression model for recall, there was a significant group_fornix interaction, indicating that the association between recall and fornix structure was weaker in patients. The opposite trend was present for the left PHC. To further investigate this pattern, two regression models were generated to account for recall performance: one based on fornix microstructure and the other on both fornix and left PHC. The realignment to PHC was positively correlated with free recall but not non-memory measures, implying a reconfiguration that is beneficial to residual memory. There was a positive relationship between realignment to PHC and basal forebrain gray matter volume despite this region demonstrating atrophy at a group level, i.e., the cognitive realignment to left PHC was most apparent when cholinergic areas were relatively spared. Therefore, cholinergic systems appear to enable adaptation to injury even as they degenerate, which has implications for functional restoration.",adult;aged;article;cholinergic system;Clinical Dementia Rating;controlled study;diffusion weighted imaging;Doors and People Test;episodic memory;female;forebrain;human;male;memory;mild cognitive impairment;Mini Mental State Examination;neuropsychological test;normal human;parahippocampal cingulum;priority journal;recall;scoring system;task performance;tractography;visual memory;white matter,"Ray, N. J.;Metzler-Baddeley, C.;Khondoker, M. R.;Grothe, M. J.;Teipel, S.;Wright, P.;Heinsen, H.;Jones, D. K.;Aggleton, J. P.;O’Sullivan, M. J.",2015,,,0,
1753,The use of olfactory receptor neurons (ORNs) from biopsies to study changes in aging and neurodegenerative diseases,"A gradual loss of olfactory capability with age and in a number of neurodegenerative diseases is common, and mechanisms underlying these losses are not understood. We determined the feasibility of using ORNs obtained from olfactory epithelial biopsies to identify possible changes in ORN function that may contribute to olfactory impairment in these individuals. ORNs from nine healthy subjects (66-84 yr), three patients with Alzheimer's disease and one with multi-infarct dementia were studied with calcium imaging techniques and two odorant mixtures. Seventy-five viable ORNs were studied; 53% of these were odorant responsive, and twenty percent of these responded to both odorant mixtures. In contrast, 25% of 173 ORNs from younger subjects were odorant responsive, and none of these responded to both odorant mixtures. The proportion of cells responding to each of the odorant mixtures also differed between older and younger subjects. These studies demonstrate the feasibility of this approach to examine age or disease-associated changes in neuronal function. Further, age-related changes in ORN selectivity may contribute to changes in olfactory performance.","Aged;Aged, 80 and over;Aging/pathology/ physiology;Biopsy;Calcium/analysis;Humans;Image Processing, Computer-Assisted;Middle Aged;Neurodegenerative Diseases/pathology/ physiopathology;Olfactory Receptor Neurons/pathology/ physiology","Rawson, N. E.;Gomez, G.;Cowart, B.;Restrepo, D.",1998,Nov 30,,0,
1754,Acute necrotizing encephalopathy presenting as a basal ganglia syndrome,"Acute necrotizing encephalopathy is a relatively new disease. The characteristic clinical findings are of febrile illness followed by rapid deterioration in mental status and seizures. The hallmark of the disease is multifocal bilateral symmetric lesions affecting the thalamus, hypothalamus, brainstem tegmentum, cerebral white matter, and cerebellum. The etiology is unknown, but immune-mediated mechanism was suggested. We present a 12-year-old previously healthy girl who developed increased sleepiness progressing to stupor and coma. Magnetic resonance imaging (MRI) of the brain showed the characteristic findings previously described in acute necrotizing encephalopathy. Her mental status improved dramatically with steroid treatment, and the MRI findings resolved completely within 6 months. Following the acute illness, she developed a complex neuropsychiatric disorder consistent with basal ganglia syndrome.",,"Ravid, S.;Topper, L.;Eviatar, L.",2001,2001,,0,
1755,Retinal migraine as unusual feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),,acetylsalicylic acid;calcium channel blocking agent;ergot alkaloid;methysergide;nimodipine;adult;article;CADASIL;case report;clinical feature;genetics;headache;human;male;migraine;missense mutation;multiinfarct dementia;nuclear magnetic resonance imaging;pedigree;syndrome;transitional blindness;visual impairment,"Ravaglia, S.;Costa, A.;Santorelli, F. M.;Nappi, G.;Moglia, A.",2004,,,0,
1756,Demographic and CT scan features related to cognitive impairment in the first year after stroke,"Objective: Little is known about the relation between stroke related features and cognitive performance over time when stroke patients with dementia or less severe cognitive disorders are considered separately. We aimed to study the features (computed tomography (CT) scan and demographic) that could be related to vascular cognitive impairment one, six, and 12 months after stroke. Methods: A total of 176 patients with a first-ever brain infarct, a Mini Mental State Examination score ≥15, age older than 40 years, and without pre-stroke dementia and other neurological or psychiatric disorders participated in this study. The following CT scan features were recorded: side of infarct, lacunar or territorial infarct, white matter lesions, silent infarcts, and brain atrophy. The demographic features studied were: age, level of education, and sex. Univariate and multivariate logistic regression analyses were performed to compare the three groups of patients (patients with dementia, patients with vascular cognitive impairment (VCI), and patients with vascular mild cognitive impairment (MCI)) with patients without cognitive disorders. Results: At one month none of the variables were predictors of dementia; at six months older age (odds ratio (OR) 9.4), low education (OR 14.7), and territorial infarct (OR 10.6) predicted dementia; and at 12 months low education (OR 8.7) and pre-stroke cerebrovascular damage (OR 7.4) predicted dementia. Predictors of VCI were low education (OR 3.4) and territorial infarct (OR 2.4) at one month post stroke; older age (OR 4.3) and low education (OR 4.1) at six months; and older age (OR 3.5) at 12 months. Predictors of vascular MCI were low education (OR 4.96) and territorial infarct (OR 3.58) at one month; and older age and lower education at six months (OR 3.4 and 3.7, respectively) and at 12 months (OR 3.5 and 2.28, respectively). Conclusions: Territorial infarct, older age, and low educational level are predictors of cognitive disorders after stroke.",academic achievement;adult;age distribution;aged;article;brain atrophy;brain infarction;brain region;clinical feature;cognition;cognitive defect;computer assisted tomography;controlled study;correlation analysis;dementia;demography;female;human;image analysis;logistic regression analysis;major clinical study;male;mental disease;Mini Mental State Examination;neurologic disease;performance;prediction;priority journal;scoring system;sex difference;cerebrovascular accident,"Rasquin, S. M. C.;Verhey, F. R. J.;Van Oostenbrugge, R. J.;Lousberg, R.;Lodder, J.",2004,,,0,
1757,Vascular mild cognitive impairment is highly prevalent after lacunar stroke but does not increase over time: A 2-year follow-up study,"Although ample research has been done into cognitive disorders occurring after stroke, relatively few data are available on the development and the course of vascularmild cognitive impairment (VMCI) after first-ever lacunar stroke. Methods: A cohort of 95 patients with a first-ever symptomaticlacunar infarct, older than 40 years, MMSE ≥15 and no other neurological or major psychiatric deficits were included. Patients were assessed (clinically and with a neuropsychological test battery) at 1 and 24 months after stroke, and CT was repeated. VMCI was diagnosed when patients had a deficit in at least one cognitive domain, in the absence of dementia. Results: Approximately 75% of the patients had VMCI at 1 month; this percentage was somewhat lower at 2 years. Only initial stroke severity was an independent predictor of VMCI after stroke. Conclusion: VMCI is highly prevalent after lacunar stroke, but does not increase during the first 2 years thereafter. Copyright © 2007 S. Karger AG.",aged;article;brain region;clinical assessment;cognitive defect;cohort analysis;computer assisted tomography;controlled study;disease severity;female;follow up;human;lacunar stroke;major clinical study;male;mental disease;multiinfarct dementia;neurologic disease;neuropsychological test;patient assessment;prevalence;priority journal;risk assessment;risk factor;cerebrovascular accident;stroke patient;symptom;vascular mild cognitive impairment,"Rasquin, S. M. C.;Van Oostenbrugge, R. J.;Verhey, F. R. J.;Lodder, J.",2007,,,0,
1758,"Anesthetic management and postoperative care of a patient with CADASIL (cerebral arteriopathy, Autosomal dominant, With subcortical infarcts and leukoencephalopathy) for cesarean section","CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) is an infrequent inherited small artery disease that could have anesthetic implications. However these have rarely been reported. We present an anesthetic experience of a female patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, mood alterations, apathy, and urine incontinence. We discuss anesthetic management of CADASIL patient, considering protection from further cerebral ischemia.",acetylsalicylic acid;anesthetic agent;atracurium besilate;fentanyl;hydralazine;insulin;methyldopa;metoclopramide;oxytocin;ranitidine;Ringer lactate solution;suxamethonium;thiopental;adult;anesthesia;article;artificial ventilation;CADASIL;case report;cesarean section;computer assisted tomography;continuous infusion;diabetes mellitus;drug substitution;drug withdrawal;female;genetic analysis;headache;human;hypertension;neurologic examination;neuromuscular blocking;nuclear magnetic resonance imaging;oxygenation;paresis;postoperative care;pregnant woman;premedication,"Rasooli, S.;Moslemi, F.;Tagavi, S.",2014,,,0,
1759,Lesion localization in periodic lateralized epileptiform discharges: Gray or white matter,"We analyzed the results of neuroimaging studies in patients with periodic lateralized epileptiform discharges (PLEDs) or bilateral independent periodic lateralized epileptiform discharges (BIPLEDs) for localization of lesions in gray or white matter to determine if 'cortical isolation' is a critical mechanism in the pathogenesis of this phenomena. We assessed 32 patients who had undergone computed tomography (CT) exclusively and 8 patients who had undergone magnetic resonance imaging (MRI) with or without CT. The superior resolution necessary for adequate lesion localization allowed use of only the MRI scans from the 8 patients. Six patients had scans with cortical and subcortical gray and white matter lesions, and 1 patient had a cortical gray matter lesion only. One patient had an indeterminate scan. No patient had white matter lesions only. Our findings in patients with PLEDs and BIPLEDs correlate with postmortem data in patients with generalized periodic EEG patterns that show consistent localization of lesions in the gray matter. These findings do not support cortical isolation as the critical or sole mechanism in PLEDs or BIPLEDs.",,"Raroque Jr, H. G.;Purdy, P.",1995,1995,,0,
1760,Neuropsychological test findings in subjects with leukoaraiosis,"Focal periventricular white-matter changes (leukoaraiosis) have been identified incidentally on brain imaging in normal healthy individuals and more commonly in the elderly and in hypertensive individuals. It has been suggested that leukoaraiosis represents the early stages of Binswanger's leukoencephalopathy, a dementing process thought to be related to hypertensive cerebrovascular disease. To test this hypothesis, extensive neuropsychological tests were administered to 50 consecutive normotensive, middle-aged, healthy volunteers. Ten subjects (20%) had white-matter changes on magnetic resonance scans; 40 subjects (80%) had normal scans. The differences observed on neuropsychological testing between subjects with and without leukoaraiosis were not significant. While this study argues against a link between leukoaraiosis and dementia, prospective longitudinal studies are needed to determine the value of leukoaraiosis in predicting future cognitive decline.",Adult;Brain/ pathology;Cognition Disorders/diagnosis;Dementia/etiology;Demyelinating Diseases/ diagnosis/psychology;Humans;Magnetic Resonance Imaging;Middle Aged;Neuropsychological Tests;Risk Factors,"Rao, S. M.;Mittenberg, W.;Bernardin, L.;Haughton, V.;Leo, G. J.",1989,Jan,,0,
1761,Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease,"Objectives: We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease. Methods: We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084). Results: Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r2 > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes. Conclusions: Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.",col4a1 protein;col4a2 protein;collagen type 4;unclassified drug;article;brain hemorrhage;brain ischemia;cerebrovascular disease;gene linkage disequilibrium;genetic association;genotype;human;meta analysis;priority journal;single nucleotide polymorphism;white matter,"Rannikmäe, K.;Davies, G.;Thomson, P. A.;Bevan, S.;Devan, W. J.;Falcone, G. J.;Traylor, M.;Anderson, C. D.;Battey, T. W. K.;Radmanesh, F.;Deka, R.;Woo, J. G.;Martin, L. J.;Jimenez-Conde, J.;Selim, M.;Brown, D. L.;Silliman, S. L.;Kidwell, C. S.;Montaner, J.;Langefeld, C. D.;Slowik, A.;Hansen, B. M.;Lindgren, A. G.;Meschia, J. F.;Fornage, M.;Bis, J. C.;Debette, S.;Ikram, M. A.;Longstreth, W. T.;Schmidt, R.;Zhang, C. R.;Yang, Q.;Sharma, P.;Kittner, S. J.;Mitchell, B. D.;Holliday, E. G.;Levi, C. R.;Attia, J.;Rothwell, P. M.;Poole, D. L.;Boncoraglio, G. B.;Psaty, B. M.;Malik, R.;Rost, N.;Worrall, B. B.;Dichgans, M.;Van Agtmael, T.;Woo, D.;Markus, H. S.;Seshadri, S.;Rosand, J.;Sudlow, C. L. M.",2015,,,0,
1762,Proposal of a new tractographic feature for analysis of white matter in Alzheimer diffusion mr images,"Alzheimer's disease (AD) is a leading cause of dementia in elderly adults. In this, the white matter (WM) tracts in brain are disintegrated leading to loss of important cognitive functionality. Recent analysis have shown that early diagnosis of AD is still a challenging task. Although several reports are available, tractography remains the most promising and clinically relevant method for in-vivo study of WM tracts. In tractography, continuous WM pathways are reconstructed from voxel based models of discrete fiber orientation generated using diffusion tensor images. In this work an attempt has been made to classify AD using average length of tracts, a significant feature extracted from tractographic brain maps. The diffusion weighted images for AD and matched controls were obtained from ADNI, an international open access repository for Alzheimer's study. Data from equal number of AD and controls were used for this study. Fiber tracking was performed for the whole brain using tract based spatial statistics algorithm. ICBM Mori Labels 1 atlas provided in the Network Analysis option of ExploreDTI was used to divide the WM into 48 anatomical regions. Classification was performed using random forest, random tree and decision stumps, and their performance indices were compared. The results show that all the classifiers are able to classify AD and controls using the extracted feature. An accuracy of 78.4% is obtained using decision stumps. Random forest and random tree provide an increased accuracy of 96% and 97% respectively. The precision and recall is also found to be higher for random forest and random tree as compared to decision stumps. These results suggest that random forest and random tree are suitable for classification of AD and controls using average tract length as a feature. In this paper, the introduction, objectives, materials and methods, results and discussions and conclusions are presented in detail.",,"Ranjan, P.;Ramakrishnan, S.",2014,,,0,
1763,Posterior reversible encephalopathy syndrome: A possible late interaction between cytotoxic agents and general anaesthesia,"A 49-year-old woman who had previously received treatment with cytotoxic drugs for metastatic gestational trophoblastic disease (GTD) presented with a witnessed tonic - clonic seizure, headache, confusion and blindness, 6 days after the uneventful administration of a general anaesthetic and 2 months after cessation of chemotherapy. Magnetic resonance imaging showed relatively symmetrical, subcortical, white matter abnormalities, predominantly affecting the occipital, posterior temporal and parietal lobes and the cerebellum. T2-dependent abnormalities and elevated regional apparent diffusion coefficient were present in a pattern typical for posterior reversible encephalopathy syndrome (PRES). The clinical and radiological manifestations were resolved completely with supportive therapy. This case of PRES may be a late complication of gemcitabine or cisplatin therapy precipitated by a general anaesthetic, or associated electrolyte or blood pressure disturbance. © Springer-Verlag 2005.",,"Rangi, P. S.;Partridge, W. J.;Newlands, E. S.;Waldman, A. D.",2005,August,,0,
1764,Inverse correspondence between hippocampal perfusion and verbal memory performance in older adults,"Understanding physiological changes that precede irreversible tissue damage in age-related pathology is central to optimizing treatments that may prevent, or delay, cognitive decline. Cerebral perfusion is a tightly regulated physiological property, coupled to tissue metabolism and function, and abnormal (both elevated and reduced) hippocampal perfusion has been reported in a range of cognitive disorders. However, the size and location of the hippocampus complicates perfusion quantification, as many perfusion techniques acquire data with spatial resolution on the order of or beyond the size of the hippocampus, and are thus suboptimal in this region (especially in the presence of hippocampal atrophy and reduced flow scenarios). Here, the relationship between hippocampal perfusion and atrophy as a function of memory performance was examined in cognitively normal healthy older adults (n = 20; age=67 ± 7 yr) with varying genetic risk for dementia using a custom arterial spin labeling acquisition and analysis procedure. When controlling for hippocampal volume, it was found that hippocampal perfusion correlated inversely (P = 0.04) with memory performance despite absent hippocampal tissue atrophy or white matter disease. The hippocampal flow asymmetry (left hippocampus perfusion-right hippocampus perfusion) was significantly (P = 0.04) increased in APOE-ε{lunate}4 carriers relative to noncarriers. These findings demonstrate that perfusion correlates more strongly than tissue volume with memory performance in cognitively normal older adults, and furthermore that an inverse trend between these two parameters suggests that elevation of neuronal activity, possibly mediated by neuroinflammation and/or excitation/inhibition imbalance, may be closely associated with minor changes in memory performance. © 2012 Wiley Periodicals, Inc.",aged;article;brain atrophy;brain blood flow;brain size;clinical article;controlled study;correlational study;female;hippocampus;human;male;nerve cell inhibition;nerve cell stimulation;nervous system inflammation;priority journal;verbal memory;white matter lesion,"Rane, S.;Ally, B. A.;Hussey, E.;Wilson, T.;Thornton-Wells, T.;Gore, J. C.;Donahue, M. J.",2013,,,0,
1765,CT perfusion as a useful tool in the evaluation of leuko-araiosis,"Background: Leuko-araiosis (LA) and dementia are common geriatric conditions but their pathogenesis and clinical significance are not completely understood. An evaluation of CT perfusion (CTP) in both these conditions can further enhance the understanding of these diseases. Methods: Twenty-one patients with LA and 21 age-matched controls were studied with CTP and assessed for their cognitive function. The subjects were classified into four groups: Group 1, with LA (n = 21); Group 2, without LA (n = 21); Group 3, with dementia (n = 7); Group 4, without dementia (n = 11). The mean cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) values were compared between groups 1 and 2, while mean CBF values were compared between groups 3 and 4. Results: Mean white matter CBF was considerably reduced in patients with LA in the frontal region by 42% (p = 0.000), basal ganglia by 37% (p = 0.000) and occipital region by 18% (p = 0.019). The mean white matter CBV was reduced in patients with LA in the frontal region by 36% (p = 0.000) and basal ganglia by 28% (p = 0.017). The mean white matter CBF was dramatically reduced in patients with dementia in the frontal region by 44% (p = 0.000), basal ganglia by 32% (p = 0.038) and occipital regions by 24% (p = 0.001). Conclusion: The CTP showed reduced white matter CBF and CBV in patients with LA. This is consistent with chronic ischemia as the pathogenesis of LA. The CTP is also a potentially important technique in the diagnosis and management of dementia, because of its ability to reveal cerebral hypoperfusion. © 2006 Biomedical Imaging and Intervention Journal. All rights reserved.",,"Ramli, N.;Ho, K. L.;Nawawi, O.;Chong, H. T.;Tan, C. T.",2006,,,0,
1766,Rapid-onset cognitive impairment due to bilateral medial-thalamic infarcts,,aged;aphasia;atherosclerosis;bilateral medial thalamic infarct;brain infarction;brain region;case report;chronic kidney disease;cognitive defect;computer assisted tomography;confusion;dementia;disease duration;disorientation;human;hypertension;letter;magnetic resonance angiography;male;neuroimaging;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident,"Ramirez-Abreu, D. G.;Law, S. W.",2011,,,0,
1767,"Lesion Explorer: a video-guided, standardized protocol for accurate and reliable MRI-derived volumetrics in Alzheimer's disease and normal elderly","Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests(1,2). However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs. LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors. While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.","Alzheimer Disease/ diagnosis/pathology;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Reference Values;Reproducibility of Results;Video Recording","Ramirez, J.;Scott, C. J.;McNeely, A. A.;Berezuk, C.;Gao, F.;Szilagyi, G. M.;Black, S. E.",2014,,10.3791/50887,0,
1768,"Subcortical hyperintensity volumetrics in Alzheimer's disease and normal elderly in the Sunnybrook Dementia Study: correlations with atrophy, executive function, mental processing speed, and verbal memory","INTRODUCTION: Subcortical hyperintensities (SHs) are radiological entities commonly observed on magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) and normal elderly controls. Although the presence of SH is believed to indicate some form of subcortical vasculopathy, pathological heterogeneity, methodological differences, and the contribution of brain atrophy associated with AD pathology have yielded inconsistent results in the literature. METHODS: Using the Lesion Explorer (LE) MRI processing pipeline for SH quantification and brain atrophy, this study examined SH volumes of interest and cognitive function in a sample of patients with AD (n = 265) and normal elderly controls (n = 100) from the Sunnybrook Dementia Study. RESULTS: Compared with healthy controls, patients with AD were found to have less gray matter, less white matter, and more sulcal and ventricular cerebrospinal fluid (all significant, P <0.0001). Additionally, patients with AD had greater volumes of whole-brain SH (P <0.01), periventricular SH (pvSH) (P <0.01), deep white SH (dwSH) (P <0.05), and lacunar lesions (P <0.0001). In patients with AD, regression analyses revealed a significant association between global atrophy and pvSH (P = 0.02) and ventricular atrophy with whole-brain SH (P <0.0001). Regional volumes of interest revealed significant correlations with medial middle frontal SH volume and executive function (P <0.001) in normal controls but not in patients with AD, global pvSH volume and mental processing speed (P <0.01) in patients with AD, and left temporal SH volume and memory (P <0.01) in patients with AD. CONCLUSIONS: These brain-behavior relationships and correlations with brain atrophy suggest that subtle, yet measurable, signs of small vessel disease may have potential clinical relevance as targets for treatment in Alzheimer's dementia.",,"Ramirez, J.;McNeely, A. A.;Scott, C. J.;Stuss, D. T.;Black, S. E.",2014,,10.1186/alzrt279,0,
1769,Dynamic Progression of White Matter Hyperintensities in Alzheimer's Disease and Normal Aging: Results from the Sunnybrook Dementia Study,"Although white matter hyperintensities (WMH), markers of cerebral small vessel disease (SVD), are believed to generally increase over time, some studies have shown sharp decreases after therapeutic intervention, suggesting that WMH progression may be more dynamic than previously thought. Our primary goal was to examine dynamic progression of WMH in a real-world sample of Alzheimer's disease (AD) patients and normal elderly (NC), with varying degrees of SVD. WMH volumes from serial magnetic resonance imaging (MRI; mean = 1.8 years) were measured from NC (n = 44) and AD patients (n = 113) with high and low SVD burden. Dynamic progression for each individual was measured using spatial overlap images to assess shrinkage, growth, and stable WMH volumes. Significant group differences were found for shrinkage (p < 0.001), growth (p < 0.001) and stable (p < 0.001) WMH, where the AD high SVD group showed the largest changes relative to low SVD and NC. Our results suggest spatial progression measured at the individual patient level may be more sensitive to the dynamic nature of WMH.",,"Ramirez, J.;McNeely, A. A.;Berezuk, C.;Gao, F.;Black, S. E.",2016,,10.3389/fnagi.2016.00062,0,
1770,Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue,"Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging;Male;Middle Aged","Ramirez, J.;Gibson, E.;Quddus, A.;Lobaugh, N. J.;Feinstein, A.;Levine, B.;Scott, C. J.;Levy-Cooperman, N.;Gao, F. Q.;Black, S. E.",2011,Jan 15,10.1016/j.neuroimage.2010.09.013,0,
1771,Visible Virchow-Robin spaces on magnetic resonance imaging of Alzheimer's disease patients and normal elderly from the Sunnybrook dementia study,"Background: Visible Virchow-Robin spaces (VRS) are commonly used markers for small vessel disease in aging and dementia. Objective: However, as previous reports were based on subjective visual ratings, the goal of this project was to validate and apply an MRI-based quantitative measure of VRS as a potential neuroimaging biomarker. Methods: A modified version of Lesion Explorer was applied to MRIs from Alzheimer's disease patients (AD: n = 203) and normal elderly controls (NC: n = 94). Inter-rater reliability, technique validity, group/gender differences, and correlations with other small vessel disease markers were examined (lacunes and white matter hyperintensities, WMH). Results: Inter-rater reliability and spatial congruence was excellent (ICC = 0.99, SI = 0.96), and VRS volumes were highly correlated with established rating scales (CS: ρ = 0.84, p < 0.001; BG: ρ = 0.75, p < 0.001). Compared to NC, AD had significantly greater volumes of WMH (p < 0.01), lacunes (p < 0.001), and VRS in the white matter (p < 0.01), but not in the basal ganglia (n.s.). Compared to women, demented and non-demented men had greater VRS in the white matter (p < 0.001), but not in the basal ganglia (n.s.). Additionally, VRS were correlated with lacunes and WMH, but only in AD (r = 0.3, p < 0.01). Conclusion: Compared to women, men may be more susceptible to greater volumes of VRS, particularly in the white matter. Results support the hypothesis that VRS in the white matter may be more related to AD-related vascular pathology compared to VRS found in the basal ganglia. Future work using this novel VRS segmentation tool will examine its potential utility as an imaging biomarker of vascular rather than parenchymal amyloid.",,"Ramirez, J.;Berezuk, C.;McNeely, A. A.;Scott, C. J. M.;Gao, F.;Black, S. E.",2015,2015,,0,
1772,Antemortem MRI findings associated with microinfarcts at autopsy,"OBJECTIVE: To determine antemortem MRI findings associated with microinfarcts at autopsy. METHODS: Patients with microinfarcts (n = 22) and patients without microinfarcts (n = 44) who underwent antemortem MRI were identified from a dementia clinic-based, population-based, and community clinic-based autopsy cohort. The microinfarct and no-microinfarct groups were matched on age at MRI, age at death, sex, APOE status, Mini-Mental State Examination score, and pathologic diagnosis of Alzheimer disease. Brain infarcts were assessed on fluid-attenuated inversion recovery (FLAIR) MRI. White matter hyperintensities on FLAIR MRI and hippocampal volumes on T1-weighted MRI were quantified using automated methods. A subset of subjects with microinfarcts (n = 15) and a matched group of subjects without microinfarcts (n = 15) had serial T1-weighted MRIs and were included in an analysis of global and regional brain atrophy rates using automated methods. RESULTS: The presence of cortical (p = 0.03) and subcortical (p = 0.02) infarcts on antemortem MRI was associated with presence of microinfarcts at autopsy. Higher numbers of cortical (p = 0.05) and subcortical (p = 0.03) infarcts on antemortem MRI were also associated with presence of microinfarcts. Presence of microinfarcts was not associated with white matter hyperintensities and cross-sectional hippocampal volume on antemortem MRI. Whole-brain and regional precuneus, motor, and somatosensory atrophy rates were higher in subjects with microinfarcts compared to subjects without microinfarcts. CONCLUSIONS: Microinfarcts increase brain atrophy rates independent of Alzheimer disease pathology. Association between microinfarct pathology and macroinfarcts on MRI suggests either common risk factors or a shared pathophysiology and potentially common preventive targets.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Atrophy/etiology/pathology;Autopsy;Cerebral Infarction/complications/diagnosis/*pathology;Female;Hippocampus/pathology;Humans;Leukoencephalopathies/*pathology;Magnetic Resonance Imaging;Male;Postmortem Changes;Prospective Studies","Raman, M. R.;Preboske, G. M.;Przybelski, S. A.;Gunter, J. L.;Senjem, M. L.;Vemuri, P.;Murphy, M. C.;Murray, M. E.;Boeve, B. F.;Knopman, D. S.;Petersen, R. C.;Parisi, J. E.;Dickson, D. W.;Jack, C. R., Jr.;Kantarci, K.",2014,Jun 3,10.1212/wnl.0000000000000471,0,
1773,White Matter Deterioration May Foreshadow Impairment of Emotional Valence Determination in Early-Stage Dementia of the Alzheimer Type,"In Alzheimer Disease (AD), non-verbal skills often remain intact for far longer than verbally mediated processes. Four (1 female, 3 males) participants with early-stage Clinically Diagnosed Dementia of the Alzheimer Type (CDDAT) and eight neurotypicals (NTs; 4 females, 4 males) completed the emotional valence determination test (EVDT) while undergoing BOLD functional magnetic resonance imaging (fMRI). We expected CDDAT participants to perform just as well as NTs on the EVDT, and to display increased activity within the bilateral amygdala and right anterior cingulate cortex (r-ACC). We hypothesized that such activity would reflect an increased reliance on these structures to compensate for on-going neuronal loss in frontoparietal regions due to the disease. We used diffusion tensor imaging (DTI) to determine if white matter (WM) damage had occurred in frontoparietal regions as well. CDDAT participants had similar behavioral performance and no differences were observed in brain activity or connectivity patterns within the amygdalae or r-ACC. Decreased fractional anisotropy (FA) values were noted, however, for the bilateral superior longitudinal fasciculi and posterior cingulate cortex (PCC). We interpret these findings to suggest that emotional valence determination and non-verbal skill sets are largely intact at this stage of the disease, but signs foreshadowing future decline were revealed by possible WM deterioration. Understanding how non-verbal skill sets are altered, while remaining largely intact, offers new insights into how non-verbal communication may be more successfully implemented in the care of AD patients and highlights the potential role of DTI as a presymptomatic biomarker.",Alzheimer;Dti;brain networks;chimeric faces;emotional valence;fMRI,"Rajmohan, R.;Anderson, R. C.;Fang, D.;Meyer, A. G.;Laengvejkal, P.;Julayanont, P.;Hannabas, G.;Linton, K.;Culberson, J.;Khan, H. M.;De Toledo, J.;Reddy, P. H.;O'Boyle, M.",2017,,,0,
1774,Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study,"BACKGROUND: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. OBJECTIVE: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. METHODS: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. RESULTS: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. CONCLUSION: Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.","Aged;Aged, 80 and over;Aging/pathology/ physiology/psychology;Alzheimer Disease/diagnostic imaging/physiopathology;Brain/ diagnostic imaging/physiopathology;Cognitive Dysfunction/diagnostic imaging/physiopathology;Coronary Disease/diagnostic imaging/physiopathology;Exercise/ physiology;Gray Matter/ diagnostic imaging/physiopathology;Humans;Image Processing, Computer-Assisted;Leisure Activities;Longitudinal Studies;Magnetic Resonance Imaging;Organ Size;Stroke/diagnostic imaging/physiopathology;United States;Aging;dementia risk;energy expenditure;neuroimaging;neuroprotection;physical activity","Raji, C. A.;Merrill, D. A.;Eyre, H.;Mallam, S.;Torosyan, N.;Erickson, K. I.;Lopez, O. L.;Becker, J. T.;Carmichael, O. T.;Gach, H. M.;Thompson, P. M.;Longstreth, W. T.;Kuller, L. H.",2016,,,0,
1775,Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study,"BACKGROUND: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. OBJECTIVE: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. METHODS: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. RESULTS: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. CONCLUSION: Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.",,"Raji, C. A.;Merrill, D. A.;Eyre, H.;Mallam, S.;Torosyan, N.;Erickson, K. I.;Lopez, O. L.;Becker, J. T.;Carmichael, O. T.;Gach, H. M.;Thompson, P. M.;Longstreth, W. T.;Kuller, L. H.",2016,Mar 11,10.3233/jad-160057,0,1774
1776,Brain structure and obesity,"Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5-25). Overweight subjects (BMI: 25-30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects.","Age Factors;Aged;Analysis of Variance;Body Mass Index;Brain/*pathology;Continental Population Groups;Diabetes Mellitus, Type 2/blood/pathology;Fasting/blood;Female;Humans;Insulin/blood;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Nerve Fibers, Unmyelinated/pathology;Obesity/blood/*pathology;Organ Size;Regression Analysis;Sex Factors","Raji, C. A.;Ho, A. J.;Parikshak, N. N.;Becker, J. T.;Lopez, O. L.;Kuller, L. H.;Hua, X.;Leow, A. D.;Toga, A. W.;Thompson, P. M.",2010,Mar,10.1002/hbm.20870,0,
1777,Regular fish consumption and age-related brain gray matter loss,"BACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk. PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders. METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease. RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis. CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.","Aged;Aged, 80 and over;Animals;Brain/metabolism;Cross-Sectional Studies;Diet;Fatty Acids, Omega-3/ administration & dosage;Female;Fishes;Gray Matter/ metabolism;Humans;Life Style;Magnetic Resonance Imaging;Male;Regression Analysis;Surveys and Questionnaires","Raji, C. A.;Erickson, K. I.;Lopez, O. L.;Kuller, L. H.;Gach, H. M.;Thompson, P. M.;Riverol, M.;Becker, J. T.",2014,Oct,10.1016/j.amepre.2014.05.037,0,
1778,"Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with Pittsburgh Compound B","We evaluated the region-to-region correlation, laterality and asymmetry of amyloid deposition in subjects with mild cognitive impairment (MCI) or Alzheimer's disease (AD) using the amyloid tracer, Pittsburgh Compound B (PiB). Seventeen subjects, including 7 with MCI (MMSE 26.7+/-2.4) and 10 with AD (MMSE of 24.8+/-2.7) underwent PiB imaging. Measures of laterality (i.e., group-wise predilection for right or left) and asymmetry (i.e., group-wise predilection for unequal PiB retention between the two hemispheres) were calculated for 17 Regions of Interest (ROIs). Regional correlations were calculated along with within-group and between-groups statistical analyses of laterality and asymmetry metrics. The median correlation between PiB retention across all pairs of ROIs was 0.65, with highest correlations found in areas of highest PiB retention (r=0.74). Overall, PiB retention was symmetric bilaterally, but there was PiB laterality in MCI in dorsal frontal cortex [(t(6)=3.05, p=0.02, L>R] and sensory-motor area [t(6)=3.10, p=0.02, L>R] and in AD in the occipital pole (t(9)=-2.63, p=0.03, R>L). The most significant asymmetries in PiB retention were found in sub-cortical white matter (t(6)=3.99, p=0.01) and middle precuneus [(t(6)=3.57, p=0.01] in MCI, and in lateral temporal cortex (t(9)=3.02, p=0.01) and anterior ventral striatum [t(9)=2.37, p=0.04] in AD. No group differences (AD versus MCI) were detected in laterality [F (1, 15)=0.15, p=0.7] or asymmetry [F (1, 15)=0.7, p=0.42].","Aged;Aged, 80 and over;Alzheimer Disease/pathology/physiopathology/ radionuclide imaging;Amyloid beta-Peptides/analysis/ metabolism;Aniline Compounds/metabolism/pharmacokinetics;Basal Ganglia/pathology/physiopathology/radionuclide imaging;Brain Mapping/methods;Cerebral Cortex/pathology/physiopathology/ radionuclide imaging;Cognition Disorders/pathology/physiopathology/ radionuclide imaging;Female;Functional Laterality/physiology;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Plaque, Amyloid/metabolism/pathology;Positron-Emission Tomography/ methods;Staining and Labeling/methods;Thiazoles/metabolism/pharmacokinetics","Raji, C. A.;Becker, J. T.;Tsopelas, N. D.;Price, J. C.;Mathis, C. A.;Saxton, J. A.;Lopresti, B. J.;Hoge, J. A.;Ziolko, S. K.;DeKosky, S. T.;Klunk, W. E.",2008,Jul 30,10.1016/j.jneumeth.2008.05.005,0,
1779,Brain Parenchymal Fraction: A Relatively Simple MRI Measure to Clinically Distinguish ALS Phenotypes,"Even though neuroimaging and clinical studies indicate that amyotrophic lateral sclerosis (ALS) manifests with distinct clinical phenotypes, no objective test exists to assess upper motor degeneration in ALS. There is great interest in identifying biomarkers of ALS to allow earlier diagnosis and to recognize disease subtypes. Current quantitative neuroimaging techniques such as T2 relaxometry and diffusion tensor imaging are time-consuming to use in clinical settings due to extensive postprocessing requirements. Therefore, we aimed to study the potential role of brain parenchymal fraction (BPF) as a relatively simple quantitative measure for distinguishing ALS phenotypes. T1-weighted MR images of brain were obtained in 15 neurological controls and 88 ALS patients categorized into 4 distinct clinical phenotypes, upper motor neuron- (UMN-) predominant ALS patients with/without corticospinal tract (CST) hyperintensity on T2/PD-weighted images, classic ALS, and ALS with frontotemporal dementia (ALS-FTD). BPF was calculated using intracranial grey matter, white matter, and cerebrospinal fluid volumes obtained in control and ALS subgroups using SPM8 software. Only ALS-FTD patients had significant reduction in BPF when compared to controls and nondemented ALS patients. Correlation of clinical measures such as disease duration with BPF further supports the view that the BPF could be a potential biomarker for clinical diagnosis of ALS-FTD patients.",,"Rajagopalan, V.;Pioro, E. P.",2015,,10.1155/2015/693206,0,
1780,Brain White Matter Shape Changes in Amyotrophic Lateral Sclerosis (ALS): A Fractal Dimension Study,"Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder. Current diagnosis time is about 12-months due to lack of objective methods. Previous brain white matter voxel based morphometry (VBM) studies in ALS reported inconsistent results. Fractal dimension (FD) has successfully been used to quantify brain WM shape complexity in various neurological disorders and aging, but not yet studied in ALS. Therefore, we investigated WM morphometric changes using FD analyses in ALS patients with different clinical phenotypes. We hypothesized that FD would better capture clinical features of the WM morphometry in different ALS phenotypes than VBM analysis. High resolution MRI T1-weighted images were acquired in controls (n = 11), and ALS patients (n = 89). ALS patients were assigned into four subgroups based on their clinical phenotypes.VBM analysis was carried out using SPM8. FD values were estimated for brain WM skeleton, surface and general structure in both controls and ALS patients using our previously published algorithm. No significant VBM WM changes were observed between controls and ALS patients and among the ALS subgroups. In contrast, significant (p<0.05) FD reductions in skeleton and general structure were observed between ALS with dementia and other ALS subgroups. No significant differences in any of the FD measures were observed between control and ALS patients. FD correlated significantly with revised ALS functional rating scale (ALSFRS-R) score a clinical measure of function. Results suggest that brain WM shape complexity is more sensitive to ALS disease process when compared to volumetric VBM analysis and FD changes are dependent on the ALS phenotype. Correlation between FD and clinical measures suggests that FD could potentially serve as a biomarker of ALS pathophysiology, especially after confirmation by longitudinal studies. © 2013 Rajagopalan et al.",,"Rajagopalan, V.;Liu, Z.;Allexandre, D.;Zhang, L.;Wang, X. F.;Pioro, E. P.;Yue, G. H.",2013,,,0,
1781,"Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment","A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy. As homocysteine promotes brain atrophy, we set out to discover whether people carrying the C677T MTHFR polymorphism which increases homocysteine, might also show systematic differences in brain structure. Using tensor-based morphometry, we tested this association in 359 elderly Caucasian subjects with mild cognitive impairment (MCI) (mean age: 75 +/- 7.1 years) scanned with brain MRI and genotyped as part of Alzheimer's Disease Neuroimaging Initiative. We carried out a replication study in an independent, non-overlapping sample of 51 elderly Caucasian subjects with MCI (mean age: 76 +/- 5.5 years), scanned with brain MRI and genotyped for MTHFR, as part of the Cardiovascular Health Study. At each voxel in the brain, we tested to see where regional volume differences were associated with carrying one or more MTHFR 'T' alleles. In ADNI subjects, carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2-8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5-1.5% per T allele at 1 year follow-up, after adjusting for age and sex. We replicated these brain volume deficits of up to 5-12% per MTHFR T allele in the independent cohort of CHS subjects. As expected, the associations weakened after controlling for homocysteine levels, which the risk gene affects. The MTHFR risk variant may thus promote brain atrophy by elevating homocysteine levels. This study aims to investigate the spatially detailed effects of this MTHFR polymorphism on brain structure in 3D, pointing to a causal pathway that may promote homocysteine-mediated brain atrophy in elderly people with MCI.",,"Rajagopalan, P.;Jahanshad, N.;Stein, J. L.;Hua, X.;Madsen, S. K.;Kohannim, O.;Hibar, D. P.;Toga, A. W.;Jack, C. R., Jr.;Saykin, A. J.;Green, R. C.;Weiner, M. W.;Bis, J. C.;Kuller, L. H.;Riverol, M.;Becker, J. T.;Lopez, O. L.;Thompson, P. M.",2012,,10.1016/j.nicl.2012.09.012,0,
1782,Homocysteine effects on brain volumes mapped in 732 elderly individuals,"Elevated homocysteine levels are a known risk factor for Alzheimer's disease and vascular disorders. Here we applied tensor-based morphometry to brain magnetic resonance imaging scans of 732 elderly individuals from the Alzheimer's Disease Neuroimaging Initiative study, to determine associations between homocysteine and brain atrophy. Those with higher homocysteine levels showed greater frontal, parietal, and occipital white matter atrophy in the entire cohort, irrespective of diagnosis, age, or sex. This association was also found when considering mild cognitive impairment individuals separately. Vitamin B supplements, such as folate, may help prevent homocysteine-related atrophy in Alzheimer's disease by possibly reducing homocysteine levels. These atrophy profiles may, in the future, offer a potential biomarker to gauge the efficacy of interventions using dietary folate supplementation.","Aged;Alzheimer Disease/ blood/ pathology;Brain/ pathology;Brain Mapping;Cognition Disorders/ blood/ pathology;Enzyme-Linked Immunosorbent Assay;Female;Homocysteine/ blood;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male","Rajagopalan, P.;Hua, X.;Toga, A. W.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.",2011,Jun 11,10.1097/WNR.0b013e328346bf85,0,
1783,Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain,"Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 +/- 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [(11)C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.",Alzheimer's disease;aging;microglia;neuroinflammation;white matter,"Raj, D.;Yin, Z.;Breur, M.;Doorduin, J.;Holtman, I. R.;Olah, M.;Mantingh-Otter, I. J.;Van Dam, D.;De Deyn, P. P.;den Dunnen, W.;Eggen, B. J. L.;Amor, S.;Boddeke, E.",2017,,,0,
1784,Radiological study of the brain at various stages of human immunodeficiency virus infection: Early development of brain atrophy,"One hundred and one persons infected with human immunodeficiency virus (HIV-1), in whom other central nervous system infections or diseases were excluded, underwent brain CT and/or MRI at various stages of HIV-1 infection: 29 were asymptomatic (ASX), 35 had lymphadenopathy syndrome (LAS), 17 had AIDS-related complex (ARC), and 20 had AIDS. A control group of 32 HIV-1-seronegative healthy persons underwent brain MRI. The most common finding was brain atrophy, found in 9% of controls, and 31% of ASX cases, 29% of LAS, 59% of ARC and 70% of AIDS. Even the difference between the ASX or LAS groups and controls was significant. The changes were bilateral and symmetrical, and they were more severe at later stages of infection. Infratentorial atrophy was seen in the early stages; supratentorial atrophy became more pronounced at ARC, and generalized atrophy was typical of AIDS. Non-specific small hyperintense foci were found on MRI in 13% of controls and 6-15% of the infected groups. Larger, diffuse, bilateral white matter infiltrates were detected in 4 demented patients with AIDS. Four patients with AIDS and 1 with LAS had focal hyperintense lesions in the internal capsules, lentiform nuclei or thalamus, often bilateral on MRI. One patient with AIDS, examined with CT only, had low density in the lentiform nucleus. Loss of brain parenchyma can occur at an early stage of HIV-1 infection, and the atrophic process becomes more intense at later stages (ARC and AIDS). Parenchymal infiltration, seen as hyperintense areas on MRI, is most often associated with severe clinical symptoms, in the later stages of the disease.",adult;AIDS related complex;article;brain atrophy;central nervous system infection;computer assisted tomography;controlled study;female;human;Human immunodeficiency virus infection;lymphadenopathy;major clinical study;male;nuclear magnetic resonance imaging;priority journal,"Raininko, R.;Elovaara, I.;Virta, A.;Valanne, L.;Haltia, M.;Valle, S. L.",1992,,,0,
1785,Data from the VITA study do not support the concept of vascular depression,"Objective: Cerebrovascular lesions that are apparent in magnetic resonance scans and regioselective atrophy of the brain have been proposed as a causative or exacerbating factor in depression with late-life onset. The objective of this study was to investigate whether deep white matter or periventricular hyperintensities, small ischemic lesions, and brain atrophy contribute to late-onset depression in the non-demented elderly. Method: Based on a group of 606 individuals of identical age (75.8 years, standard deviation: 0.45 years) residing in two districts of Vienna, the authors built a case-control cohort (ratio: 1:4) consisting of 51 individuals with late-onset major or minor depression matched with 204 subjects of identical gender and education status without depression, resulting in two groups that were homogenous with respect to age, place of residence, gender, and education. Scores for focal brain lesions, mediotemporal lobe atrophy, and ventricular enlargement as well as risk factors for vascular disease were compared with cognition and depression status. Results: Depressed individuals had significantly lower scores than nondepressed subjects in all measures of cognitive and executive function. No significant relation was found between a diagnosis of depression and any type of discrete brain lesions, but measures of brain atrophy (Cella Media indices, mediotemporal atrophy) showed a clear statistical relation to depression. No relationship was found between depression and lipid parameters. Conclusion: The authors found no indication that white matter hyperintensities or minor ischemic lesions played a role in our depressed cohort, casting doubt on the vascular hypothesis of late-onset depression. © 2006 American Association for Geriatric Psychiatry.",adult;aged;aging;article;brain atrophy;brain function;brain mapping;cerebrovascular disease;cohort analysis;dementia;depression;female;human;image analysis;lipid blood level;major clinical study;male;nuclear magnetic resonance imaging;vascular disease,"Rainer, M. K.;Mucke, H. A. M.;Zehetmayer, S.;Krampla, W.;Kuselbauer, T.;Weissgram, S.;Jungwirth, S.;Tragl, K. H.;Fischer, P.",2006,,,0,
1786,Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in communities study,"BACKGROUND: Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age. RESULTS: In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al. and Horvath) from DNA methylation measured using the Illumina HM450 array on genomic DNA extracted from blood. Age acceleration, calculated as the residual values from the regression of each of the predicted age measures onto the chronologic age, was significantly associated with WMH burden after accounting for chronologic age and sex, body mass index, systolic blood pressure, hypertension, diabetes, current smoking, and blood cell composition, and results were similar for either Hannum et al.- or Horvath-derived estimates (P = 0.016 and 0.026). An age acceleration increase by 1 year was associated with an increase of WMH burden by ~1 grade. To shed light on possible biological mechanisms underlying this association, we conducted a genome-wide association study of age acceleration and identified four loci harboring genes implicated in hemostasis, cell proliferation, protein degradation, and histone methylation. However, none of these loci were associated with WMH burden. CONCLUSIONS: In this population-based study of middle-aged to older African-American adults, we report an association between accelerated epigenetic aging and increased WMH burden, independent of known risk factors, including chronologic age. Additional studies are needed to clarify whether DNA methylation age reflects biological mechanisms implicated in the aging of the cerebral white matter.",Aging;Cerebrovascular disease;DNA methylation;Epigenetic age acceleration;Epigenetic clock;White matter hyperintensities,"Raina, A.;Zhao, X.;Grove, M. L.;Bressler, J.;Gottesman, R. F.;Guan, W.;Pankow, J. S.;Boerwinkle, E.;Mosley, T. H.;Fornage, M.",2017,,,0,
1787,Multiple brain infarctions in a young patient with Buerger's disease. A case report of cerebral thromboangiitis obliterans,"We report a 46-year-old woman with Buerger's disease who presented vascular dementia. In her early thirties, she began to feel cold sensation and pain in the lower extremities and later developed Raynaud's phenomenon in the upper extremities. The diagnosis of Buerger's disease was established on the basis of angiographic findings which showed the obstruction of peripheral vessels in both anterior tibial arteries. She was admitted to our hospital because of a transient attack of left brachial monoparesis and two episodes of epileptic seizure with progressive cognitive impairment for preceding five years. Neurological examination revealed acalculia, constructional apraxia, recent memory disturbance, and hyperreflexia of the left limbs without motor disturbance. Brain MRI revealed multiple infarctions mainly located in the border zone territories of the major cerebral arteries. Conventional angiography failed to detect abnormalities of cerebral vessels. She had no cardiovascular abnormality or coagulopathy. Cerebrovascular complications, so-called cerebral thoromboangiitis obliterans (CTAO), occur approximately in 2% of patients with Buerger's disease. CTAO has two types. Type 1 is associated with large artery changes and type 2 is associated with medium and small artery changes. Patients with type 2 CTAO usually have multiple infarcts in the cerebral arterial border zones and may develop progressive cognitive decline without motor deficit. Her clinical features are compatible with type 2 CTAO. While CTAO is a relatively rare manifestation of Buerger's disease, it should be suspected in cases of Buerger's disease in association with cognitive impairment of unknown onset.",adult;angiography;apraxia;article;brain infarction;Buerger disease;case report;clinical feature;cognitive defect;cold sensation;female;human;hyperreflexia;memory disorder;motor dysfunction;multiinfarct dementia;nuclear magnetic resonance imaging;Raynaud phenomenon;seizure,"Rai, M.;Miyashita, K.;Oe, H.;Nishigami, K.;Naritomi, H.",2004,,,0,
1788,Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior disorder,"Idiopathic rapid eye movement sleep behavior disorder is a parasomnia that is a risk factor for dementia with Lewy bodies and Parkinson's disease. Brain function impairments have been identified in this disorder, mainly in the frontal and posterior cortical regions. However, the anatomical support for these dysfunctions remains poorly understood. We investigated gray matter thickness, gray matter volume, and white matter integrity in patients with idiopathic rapid eye movement sleep behavior disorder. Twenty-four patients with polysomnography-confirmed idiopathic rapid eye movement sleep behavior disorder and 42 healthy individuals underwent a 3-tesla structural and diffusion magnetic resonance imaging examination using corticometry, voxel-based morphometry, and diffusion tensor imaging. In the patients with idiopathic rapid eye movement sleep behavior disorder, decreased cortical thickness was observed in the frontal cortex, the lingual gyrus, and the fusiform gyrus. Gray matter volume was reduced in the superior frontal sulcus only. Patients showed no increased gray matter thickness or volume. Diffusion tensor imaging analyses revealed no significant white matter differences between groups. Using corticometry in patients with idiopathic rapid eye movement sleep behavior disorder, several new cortical regions with gray matter alterations were identified, similar to those reported in dementia with Lewy bodies and Parkinson's disease. These findings provide some anatomical support for previously identified brain function impairments in this disorder.","Aged;Cerebral Cortex/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Polysomnography;REM Sleep Behavior Disorder/ pathology","Rahayel, S.;Montplaisir, J.;Monchi, O.;Bedetti, C.;Postuma, R. B.;Brambati, S.;Carrier, J.;Joubert, S.;Latreille, V.;Jubault, T.;Gagnon, J. F.",2015,Apr 15,10.1002/mds.25820,0,
1789,Parkinsonism in a pair of monozygotic CADASIL twins sharing the R1006C mutation: a transcranial sonography study,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson’s disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features.",antihypertensive agent;carbidopa plus levodopa;ioflupane i 123;Notch3 receptor;aged;arterial wall thickness;article;blood analysis;blood pressure monitoring;bradykinesia;brain damage;CADASIL;case report;cerebrospinal fluid analysis;confusion;Doppler ultrasonography;electrocardiogram;fever;gene;gene mutation;genetic analysis;headache;human;hypertension;lacunar stroke;male;mild cognitive impairment;Mini Mental State Examination;monozygotic twins;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;parkinsonism;single photon emission computer tomography;transcranial Doppler ultrasonography;Unified Parkinson Disease Rating Scale,"Ragno, M.;Sanguigni, S.;Manca, A.;Pianese, L.;Paci, C.;Berbellini, A.;Cozzolino, V.;Gobbato, R.;Peluso, S.;De Michele, G.",2016,,,0,
1790,Anxiety disorder as the sole clinical manifestation of a new CADASIL mutation associated with occasional GOM deposits,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary disease of small cerebral vessels. The defective gene involved is NOTCH3. The main clinical manifestations of CADASIL include recurrent transient ischemic attacks, stroke, cognitive impairment, epilepsy, and migraine. Psychiatric symptoms, especially mood disturbances, are also described in CADASIL patients. Aims of the study: Our aim was to understand if CADASIL may be diagnosed in patients with typical white-matter MRI abnormalities but with anxiety disorder as the sole clinical manifestation. Methods: A 76-year-old woman who suffered from anxiety was recruited. Genetic analysis for NOTCH3 gene mutations and morphological examination by electron microscopy of a skin biopsy for the detection of deposits of granular osmiophilic material (GOM) in small and medium sized arteries were performed. Results: The patient was diagnosed with CADASIL, leading to discovery of a new heterozygous missense mutation (p.C875R) in NOTCH3 gene. Despite being a common mutation, it has never to our knowledge been described in exon 17 of NOTCH3 gene. Interestingly, it is associated with occasional GOM deposits. Conclusions: Since CADASIL is often underdiagnosed, it is important that psychiatrists consider this potential differential diagnosis in patients with typical white-matter MRI abnormalities.",benzodiazepine;cyanocobalamin;epidermal growth factor;folic acid;Notch3 receptor;adult;aged;anxiety disorder;article;brain deposit;brain disease;CADASIL;case report;computer assisted tomography;disease association;echocardiography;electromyography;electron microscopy;electroneurography;esophagogastroduodenoscopy;female;gait;gene mutation;genetic analysis;granular osmiophilic material;histopathology;human;human tissue;limb dysesthesia;middle aged;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;radiculopathy;skin biopsy;stomach biopsy,"Ragno, M.;Pianese, L.;Paci, C.;Sanguigni, S.;Cozzolino, V.;Lorenzi, T.;Trojano, L.;Morroni, M.",2016,,,0,
1791,"""CADASIL coma"" in an Italian homozygous CADASIL patient: Comparison with clinical and MRI findings in age-matched heterozygous patients with the same G528C NOTCH3 mutation","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disorder caused by mutations in the NOTCH3 gene, with a striking variability in phenotypic expression. To date, only two homozygous patients have been reported, with divergent phenotypic features. We describe an Italian CADASIL patient, homozygous for G528C mutation, in whom early manifestation of the disease was migraine, but whose clinical evolution was characterized by a reversible acute encephalopathy followed by full recovery (""CADASIL coma""). Clinical evaluation, MR scan, neuropsychological and neurophysiological investigation did not reveal substantial differences between our homozygous patient and her heterozygous relatives sharing the same mutation, or between our patient and a group of heterozygous individuals with the same mutation but from different families. Skin biopsy identified peculiar features in the homozygous patient, with cytoplasmic pseudoinclusions likely containing granular osmiophilic material (GOM) in the vascular smooth muscle cells, but further studies are necessary to substantiate their possible relationships with CADASIL homozygosis. ""CADASIL coma"" did not seem to be specific of patient's homozygosis, since it was observed in one of her heterozygous relatives, whereas its pathogenesis seems to be related to peculiar constellations of unknown predisposing factors. The present study demonstrated that CADASIL conforms to the classical definition of dominant diseases, according to which homozygotes and heterozygotes for a defect are phenotypically indistinguishable. © 2013 Springer-Verlag Italia.",aciclovir;anticonvulsive agent;ceftriaxone;dexamethasone;Notch3 receptor;acute brain disease;adult;amino acid substitution;aphasia;article;CADASIL;case report;delirium;DNA determination;electroencephalogram;female;fever;genetic predisposition;headache;hemianopia;hemiparesis;heterozygosity;homozygosity;human;human tissue;memory disorder;migraine;missense mutation;mutational analysis;notch3 gene;nuclear magnetic resonance imaging;paresthesia;pathogenesis;phenotype;skin biopsy;tonic clonic seizure;vascular smooth muscle,"Ragno, M.;Pianese, L.;Morroni, M.;Cacchiò, G.;Manca, A.;Di Marzio, F.;Silvestri, S.;Miceli, C.;Scarcella, M.;Onofrj, M.;Trojano, L.",2013,,,0,
1792,Multi-organ investigation in 16 CADASIL families from central Italy sharing the same R1006C mutation,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.","Adult;Aged;Aged, 80 and over;Arginine/*genetics;CADASIL/blood/complications/diagnosis/*genetics;Cardiovascular Abnormalities/etiology;Cholesterol/metabolism;Creatine Kinase/blood;Cysteine/*genetics;Disease Progression;Electromyography;*Family Health;Female;Gene Frequency;Genotype;Humans;Italy;Magnetic Resonance Imaging;Male;Middle Aged;Muscle, Skeletal/physiopathology;Mutation/*genetics;Neural Conduction;Neurophysiology;Neuropsychological Tests;Phenotype;Receptors, Notch/*genetics;Tomography, X-Ray Computed","Ragno, M.;Pianese, L.;Cacchio, G.;Manca, A.;Scarcella, M.;Silvestri, S.;Di Marzio, F.;Caiazzo, A. R.;Silvaggio, F.;Tasca, G.;Mirabella, M.;Trojano, L.",2012,Jan 6,10.1016/j.neulet.2011.10.062,0,
1793,Two novel Italian CADASIL families from Central Italy with mutation CGC-TGC at codon 1006 in the exon 19 Notch3 gene,"Here we describe clinical, neuropsychological and neuroradiological findings in 6 subjects belonging to two unrelated Italian cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) kindreds from the same geographic area who shared a common Arg1006Cys mutation. Subjects from Family A were virtually asymptomatic, and yet showed MRI pathological findings and a cluster of sub-clinical neuropsychological defects mainly centred on the visuospatial domain; patients from Family B had presented several clinically relevant episodes and showed a general cognitive impairment compatible with the clinical picture of vascular dementia. The present clinical observations are consistent with the hypothesis of a geographical clustering for CADASIL, and highlight that sub-clinical cognitive impairment may help to identify this syndrome in families presenting with only migraine.","Aged;Arginine/*genetics;CADASIL/*genetics/physiopathology;Cysteine/*genetics;DNA Mutational Analysis/methods;Exons;*Family Health;Female;Humans;Italy;Male;Middle Aged;*Mutation;Neuropsychological Tests/statistics & numerical data;Receptors, Notch/*genetics","Ragno, M.;Fabrizi, G. M.;Cacchio, G.;Scarcella, M.;Sirocchi, G.;Selvaggio, F.;Taioli, F.;Ferrarini, M.;Trojano, L.",2006,Sep,10.1007/s10072-006-0679-7,0,
1794,"Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation","BACKGROUND AND PURPOSE: To describe parkinsonism as a clinical manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. METHODS: We report 5 patients carrying the R1006C mutation in the exon 19 of NOTCH3 gene. All cases presented late onset, slowly progressive parkinsonism, not responsive to l-dopa. We performed brain MRI and (123)I-FP-CIT SPECT in all and in 3 additional patients carrying the same mutation but without parkinsonism. Four patients with parkinsonism underwent myocardial (123)I-meta-iodobenzylguanidine scintigraphy. RESULTS: In all patients, brain MRI showed widespread ischemic lesions in the periventricular white matter, the internal and external capsules, the basal ganglia, and thalami. (123)I-FP-CIT SPECT showed symmetrical or asymmetrical reduction of tracer uptake in the putamen, with inconstant caudate involvement. Myocardial (123)I-meta-iodobenzylguanidine scintigraphy resulted normal. Nigrostriatal denervation was also demonstrated in 2 patients without parkinsonism. CONCLUSIONS: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, parkinsonism may be a not rare, late onset manifestation. The clinical picture, the lack of response to dopaminergic treatment, and MRI findings suggest a vascular parkinsonism, which may be preceded by a protracted presymptomatic phase.","Aged;Brain/pathology;CADASIL/*complications/genetics/*physiopathology;Exons;Female;Genetic Predisposition to Disease;Humans;Italy;Leukoencephalopathies/genetics;Levodopa/pharmacology;Magnetic Resonance Imaging/methods;Male;*Mutation;Parkinsonian Disorders/*complications/*genetics;Receptors, Notch/*genetics;Tomography, Emission-Computed, Single-Photon/methods","Ragno, M.;Berbellini, A.;Cacchio, G.;Manca, A.;Di Marzio, F.;Pianese, L.;De Rosa, A.;Silvestri, S.;Scarcella, M.;De Michele, G.",2013,Apr,10.1161/strokeaha.111.000458,0,
1795,Biomarkers of neurological status in HIV infection: A 3-year study,"Purpose: To evaluate circulating cytokines and chemokines as correlates of the degree of brain injury in individuals with advanced human immunodeficiency virus (HIV) infection. Experimental design: Study participants included ten well-characterized subjects in advanced stage HIV infection. High-throughput multiplexed analysis was used to quantify markers of interest at baseline and 3 years later in the clinical course. Objective measurements of the brain were derived in vivo with quantitative magnetic resonance segmentation algorithms and with diffusion tensor imaging. Results: Of the markers examined, monocyte chemoattractant protein-1 (MCP-1 or CCL-2) was the most prominent correlate of brain injury. Elevated MCP-1 levels correlated with brain white matter alterations at the initial assessment. The relationship to injury was more extensive 3 years later; elevated MCP-1 was significantly correlated with measures of brain microstructural alterations and of abject atrophy. Conclusions and clinical relevance: The findings build on our prior observations that elevated MCP-1 levels may be a useful predictive marker for HIV-associated neurocognitive disorder. As a potent chemoattractant, MCP-1 may mediate injury through participation in self-reinforcing cycles of chronic immune activation and cytokine/chemokine-mediated neurotoxicity. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",,"Ragin, A. B.;Wu, Y.;Ochs, R.;Scheidegger, R.;Cohen, B. A.;Edelman, R. R.;Epstein, L. G.;McArthur, J.",2010,March,,0,
1796,Computed tomography; nuclear medicine interface in the brain,"A few conclusions can be drawn regarding the relative role of the two procedures. CT should be utilized as the initial procedure to study patients suspected of having dementia, intracerebral bleeding, glioma, or lesions in the sella and the parasellar areas and in the brain stem. CT and RBS appear to be equally as sensitive in detecting patients with metastatic lesions or meningiomas. RBS, especially in conjunction with radionuclide angiogram, is ideally suited to study patients suspected of having AVM. Once the diagnosis of AVM has been established, sequential dynamic imaging to evaluate the response to treatment (embolization or surgery) may be performed with the help of a computer, which can quantify the flow through the AVM. Dynamic imaging is also useful in studying the cerebral circulation. The two procedures appear to be complementary in such disease entities as subdural hematoma, cerebral inflammatory process, and ischemic infarction. Radionuclide cisternography and CT appear to have complementary roles in the evaluation of patients with suspected normal-pressure hydrocephalus.",,"Raghavendra, B. N.;Passalaqua, A. M.;Braunstein, P.;Pinto, R. S.",1978,1978,,0,
1797,Cerebral amyloid angiopathy-related inflammation: A potentially reversible cause of dementia with characteristic imaging findings,"BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy with inflammation (CAA-I) is a less well-recognized clinically and radiologically distinct subtype of CAA. We aim to describe the imaging manifestations of this uncommon entity. MATERIALS AND METHODS: A retrospective review of the medical records and imaging database yielded 9 patients with clinical and radiological findings compatible with CAA-I. The neurological findings at presentation, MRI findings including the presence of white matter involvement, mass effect, microhemorrhages and contrast enhancement, treatment provided and outcome were evaluated. Brain biopsy specimens, when available were also reviewed. RESULTS: All patients presented with subacute cognitive decline. In all 9 patients, confluent white matter lesions with mass effect were observed. Eight out of 9 patients demonstrated foci of microhemorrhage, while in 1, the microhemorrhages appeared 12 weeks after the initial examination. No significant parenchymal or meningeal enhancement was present in any patient. In 4 patients, brain biopsy was consistent with CAA-I. Immunosuppressive therapy was initiated in all patients, leading to full recovery in 5. CONCLUSION: CAA-I is characterized by the subacute onset of dementia, a distinct pattern of confluent white matter signal abnormality with mass effect and response to immunosuppressive therapy. Prompt recognition may help obviate brain biopsy and initiation of treatment.",,"Raghavan, P.;Looby, S.;Bourne, T. D.;Wintermark, M.",2016,Feb,10.1016/j.neurad.2015.07.004,0,
1798,Heritability and genetic association analysis of neuroimaging measures in the Diabetes Heart Study,"Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single-nucleotide polymorphisms (SNPs), and SNP data from genome- and exome-wide arrays were explored. All neuroimaging measures analyzed were significantly heritable (ĥ2= 0.55-0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p= 3.66× 10-7) and gray matter mean diffusivity (p= 2.14× 10-7). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities.",ADRB2 gene;aged;article;body mass;EBF1 gene;exome;female;gene;gene linkage disequilibrium;genetic association;genetic variability;genome analysis;genotype;gray matter;heredity;heritability;HMGCR gene;human;hypertension;male;neuroimaging;non insulin dependent diabetes mellitus;NRG3 gene;phenotype;PLEKHG4B gene;priority journal;risk factor;single nucleotide polymorphism;white matter,"Raffield, L. M.;Cox, A. J.;Hugenschmidt, C. E.;Freedman, B. I.;Langefeld, C. D.;Williamson, J. D.;Hsu, F. C.;Maldjian, J. A.;Bowden, D. W.",2015,,,0,
1799,Associations between anxiety and depression symptoms and cognitive testing and neuroimaging in type 2 diabetes,"AIMS: Anxiety, depression, accelerated cognitive decline, and increased risk of dementia are observed in individuals with type 2 diabetes. Anxiety and depression may contribute to lower performance on cognitive tests and differences in neuroimaging observed in individuals with type 2 diabetes. METHODS: These relationships were assessed in 655 European Americans with type 2 diabetes from 504 Diabetes Heart Study families. Participants completed cognitive testing, brain magnetic resonance imaging, the Brief Symptom Inventory Anxiety subscale, and the Center for Epidemiologic Studies Depression-10. RESULTS: In analyses adjusted for age, sex, educational attainment, and use of psychotropic medications, individuals with comorbid anxiety and depression symptoms had lower performance on all cognitive testing measures assessed (p</=0.005). Those with both anxiety and depression also had increased white matter lesion volume (p=0.015), decreased gray matter cerebral blood flow (p=4.43x10(-6)), decreased gray matter volume (p=0.002), increased white and gray matter mean diffusivity (p</=0.001), and decreased white matter fractional anisotropy (p=7.79x10(-4)). These associations were somewhat attenuated upon further adjustment for health status related covariates. CONCLUSIONS: Comorbid anxiety and depression symptoms were associated with cognitive performance and brain structure in a European American cohort with type 2 diabetes.",,"Raffield, L. M.;Brenes, G. A.;Cox, A. J.;Freedman, B. I.;Hugenschmidt, C. E.;Hsu, F. C.;Xu, J.;Wagner, B. C.;Williamson, J. D.;Maldjian, J. A.;Bowden, D. W.",2016,Jan-Feb,10.1016/j.jdiacomp.2015.09.010,0,
1800,Comparison of angiographic and CT findings between patients with multi-infarct dementia and those with dementia due to primary neuronal degeneration,The CT and angiographic appearances in multi-infarct dementia have been compared with those of primary neuronal degeneration. It was possible to make a CT or angiographic diagnosis of multi-infarct dementia in about 40% of patients diagnosed by the ischaemic scoring method of Hachinski et al.,"Atrophy;Brain/pathology/radiography;Brain Diseases/complications;*Cerebral Angiography;Cerebral Infarction/complications;Humans;Neurocognitive Disorders/etiology;*Tomography, X-Ray Computed","Radue, E. W.;du Boulay, G. H.;Harrison, M. J.;Thomas, D. J.",1978,,,0,
1801,Creutzfeldt-Jakob disease in a recipient of cadaveric dural graft: First observation in Austria,"Dura mater grafts can lead to Creutzfeldt-Jakob disease (CJD) as late complication (dura-CJD). So far 61 dura-CJD cases have been described worldwide. We report here the first dura-CJD case in Austria. A 50-year-old man had a traumatic open fronto-basal skull fracture with tearing of dura mater in 1977. Reconstructive surgery used Lyodura® (Braun Melsungen AG, BRD). Lyodura® was derived from pooled cadaveric dura. Ten years after the dural transplantation, the patient developed gait ataxia, paresthesia of both legs, myoclonus and visual disturbance. CT was unremarkable. EEG showed diffuse unspecific changes. The patient died 5 months after onset of disease. Neuropathological examination showed typical histopathology of CJD. Immunocytochemistry detected typical synaptic type prion protein (PrP) deposits and scattered PrP plaques in cerebral and cerebellar cortex, basal ganglia and spinal cord. Cerebellar white matter contained numerous PrP miniplaques. This pattern is unusual for sporadic CJD, but is similar to that in CJD after human growth hormone treatment. In our patient and 13/19 earlier described cases with dural graft covering the cerebrum ('central inoculation'), cerebellar disturbance was the initial symptom. Therefore, cerebellar signs are characteristic as initial symptoms in iatrogenic CJD, irrespective of central (cerebral dura mater graft) or peripheral inoculation (e.g. human growth hormone treatment). These data do not support the hypothesis that primary cerebellar symptoms in iatrogenic CJD after peripheral inoculation reflect migration of the infectious agent from the periphery via spinal cord and cerebellum to the cerebrum.",biomaterial;lyodura;adult;article;cadaver;case report;cerebellum disease;Creutzfeldt Jakob disease;dura mater;graft infection;human;infectious complication;male;prion disease;skull fracture;skull surgery,"Radbauer, C.;Hainfellner, J. A.;Gaudernak, T.;Deecke, L.;Budka, H.",1998,,,0,
1802,"Association of longitudinal white matter degeneration and cerebrospinal fluid biomarkers of neurodegeneration, inflammation and Alzheimer's disease in late-middle-aged adults","Alzheimer's disease (AD) is characterized by substantial neurodegeneration, including both cortical atrophy and loss of underlying white matter fiber tracts. Understanding longitudinal alterations to white matter may provide new insights into trajectories of brain change in both healthy aging and AD, and fluid biomarkers may be particularly useful in this effort. To examine this, 151 late-middle-aged participants enriched with risk for AD with at least one lumbar puncture and two diffusion tensor imaging (DTI) scans were selected for analysis from two large observational and longitudinally followed cohorts. Cerebrospinal fluid (CSF) was assayed for biomarkers of AD-specific pathology (phosphorylated-tau/Abeta42 ratio), axonal degeneration (neurofilament light chain protein, NFL), dendritic degeneration (neurogranin), and inflammation (chitinase-3-like protein 1, YKL-40). Linear mixed effects models were performed to test the hypothesis that biomarkers for AD, neurodegeneration, and inflammation, or two-year change in those biomarkers, would be associated with worse white matter health overall and/or progressively worsening white matter health over time. At baseline in the cingulum, phosphorylated-tau/Abeta42 was associated with higher mean diffusivity (MD) overall (intercept) and YKL-40 was associated with increases in MD over time. Two-year change in neurogranin was associated with higher mean diffusivity and lower fractional anisotropy overall (intercepts) across white matter in the entire brain and in the cingulum. These findings suggest that biomarkers for AD, neurodegeneration, and inflammation are potentially important indicators of declining white matter health in a cognitively healthy, late-middle-aged cohort.",Biomarkers;Cerebrospinal fluid;Linear mixed effects;Longitudinal;Preclinical Alzheimer's disease;White matter,"Racine, A. M.;Merluzzi, A. P.;Adluru, N.;Norton, D.;Koscik, R. L.;Clark, L. R.;Berman, S. E.;Nicholas, C. R.;Asthana, S.;Alexander, A. L.;Blennow, K.;Zetterberg, H.;Kim, W. H.;Singh, V.;Carlsson, C. M.;Bendlin, B. B.;Johnson, S. C.",2017,Jun 9,,0,
1803,Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife,"The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 +/- 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-beta42/amyloid-beta40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials.",cerebrospinal fluid;cluster analysis;longitudinal;neuroimaging;preclinical Alzheimer's disease,"Racine, A. M.;Koscik, R. L.;Berman, S. E.;Nicholas, C. R.;Clark, L. R.;Okonkwo, O. C.;Rowley, H. A.;Asthana, S.;Bendlin, B. B.;Blennow, K.;Zetterberg, H.;Gleason, C. E.;Carlsson, C. M.;Johnson, S. C.",2016,Aug,10.1093/brain/aww142,0,
1804,Associations between white matter microstructure and amyloid burden in preclinical Alzheimer's disease: A multimodal imaging investigation,"Some cognitively healthy individuals develop brain amyloid accumulation, suggestive of incipient Alzheimer's disease (AD), but the effect of amyloid on other potentially informative imaging modalities, such as Diffusion Tensor Imaging (DTI), in characterizing brain changes in preclinical AD requires further exploration. In this study, a sample (N = 139, mean age 60.6, range 46 to 71) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), a cohort enriched for AD risk factors, was recruited for a multimodal imaging investigation that included DTI and [C-11]Pittsburgh Compound B (PiB) positron emission tomography (PET). Participants were grouped as amyloid positive (Aβ+), amyloid indeterminate (Aβi), or amyloid negative (Aβ-) based on the amount and pattern of amyloid deposition. Regional voxel-wise analyses of four DTI metrics, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), and radial diffusivity (Dr), were performed based on amyloid grouping. Three regions of interest (ROIs), the cingulum adjacent to the corpus callosum, hippocampal cingulum, and lateral fornix, were selected based on their involvement in the early stages of AD. Voxel-wise analysis revealed higher FA among Aβ+ compared to Aβ- in all three ROIs and in Aβi compared to Aβ- in the cingulum adjacent to the corpus callosum. Follow-up exploratory whole-brain analyses were consistent with the ROI findings, revealing multiple regions where higher FA was associated with greater amyloid. Lower fronto-lateral gray matter MD was associated with higher amyloid burden. Further investigation showed a negative correlation between MD and PiB signal, suggesting that Aβ accumulation impairs diffusion. Interestingly, these findings in a largely presymptomatic sample are in contradistinction to relationships reported in the literature in symptomatic disease stages of Mild Cognitive Impairment and AD, which usually show higher MD and lower FA. Together with analyses showing that cognitive function in these participants is not associated with any of the four DTI metrics, the present results suggest an early relationship between PiB and DTI, which may be a meaningful indicator of the initiating or compensatory mechanisms of AD prior to cognitive decline. © 2014 Elsevier Inc.",,"Racine, A. M.;Adluru, N.;Alexander, A. L.;Christian, B. T.;Okonkwo, O. C.;Oh, J.;Cleary, C. A.;Birdsill, A.;Hillmer, A. T.;Murali, D.;Barnhart, T. E.;Gallagher, C. L.;Carlsson, C. M.;Rowley, H. A.;Dowling, N. M.;Asthana, S.;Sager, M. A.;Bendlin, B. B.;Johnson, S. C.",2014,2014,,0,
1805,Rapidly Progressive Dementia Due to Bilateral Internal Carotid Artery Occlusion with Infarction of the Total Length of the Corpus Callosum,"The authors report a patient with rapidly progressive cognitive decline due to bilateral internal carotid artery occlusion (ICAO) resulting in multiple pathologically proven cerebral infarctions including the entire length of the corpus callosum. The gradual evolution of the deficits was suggestive of hemodynamic ischemia. Bilateral ICAO should be considered in the differential diagnosis of patients with rapidly cognitive decline. Although ICAO commonly spares the splenium, complete callosal infarction is possible in the presence of bilateral ICAO.",adult;article;blood vessel reactivity;brain angiography;brain infarction;carotid artery obstruction;case report;cognition;computer assisted tomography;corpus callosum;dementia;disease course;human;internal carotid artery occlusion;male;neuroimaging;nuclear magnetic resonance imaging,"Rabinstein, A. A.;Romano, J. G.;Forteza, A. M.;Koch, S.",2004,,,0,
1806,Cortical magnetic resonance imaging changes in elderly inpatients with major depression,"OBJECTIVE: The purpose of the study was to determine if magnetic resonance imaging (MRI) scans of elderly depressed patients differ from MRI scans of age-matched control subjects and age-matched patients with Alzheimer's disease. METHOD: The authors studied 21 patients 60 years or older with major depression, 16 patients with Alzheimer's disease, and 14 age-matched control subjects. RESULTS: Compared to control subjects, depressed patients had greater cerebral sulcal and temporal sulcal atrophy; larger sylvian fissures, lateral ventricles, third ventricles, and temporal horns; and greater severity of subcortical white matter lesions. Depressed patients also had more basal ganglia lesions but similar levels of periventricular hyperintensity. There were no differences between depressed patients with and without delusions on any MRI measure. Depressed patients who received ECT had more temporal horn atrophy and greater subcortical abnormality summary scores than normal subjects. Cortical sulcal atrophy correlated with age at onset of depression. CONCLUSIONS: The findings suggest that elderly hospitalized depressed patients have greater cortical as well as subcortical atrophy and more basal ganglia lesions than age-matched normal control subjects. The correlation of these abnormalities with outcome remains unknown.","Aged;Alzheimer Disease/diagnosis/pathology;Atrophy/diagnosis/pathology;Basal Ganglia/pathology;Cerebral Cortex/ pathology;Depressive Disorder/ diagnosis/pathology;Diagnosis, Differential;Hospitalization;Humans;Magnetic Resonance Imaging;Temporal Lobe/pathology","Rabins, P. V.;Pearlson, G. D.;Aylward, E.;Kumar, A. J.;Dowell, K.",1991,May,10.1176/ajp.148.5.617,0,
1807,Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer's disease?,"Introduction The search for a reliable neuroimaging biomarker in Alzheimer's disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer's disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer's disease, amnestic mild cognitive impairment due to Alzheimer's disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ϵ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer's disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer's disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer's disease presented a higher prevalence of apolipoprotein E allele ϵ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ϵ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer's disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases.",amyloid beta protein;apolipoprotein E;tau protein;aged;Alzheimer disease;article;brain hemorrhage;clock drawing test;controlled study;diabetes mellitus;disease association;dyslipidemia;enzyme immunoassay;female;genotyping technique;human;hypertension;language test;Luria-Nebraska neuropsychological battery;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;prevalence;Rey auditory verbal learning test;Rey Osterrieth complex figure test;Stroop test;susceptibility weighted imaging;trail making test,"Rabelo, A. G. B.;Teixeira, C. V. L.;Magalhães, T. N. C.;Carletti-Cassani, A. F. M. K.;Amato Filho, A. C. S.;Joaquim, H. P. G.;Talib, L. L.;Forlenza, O.;Ribeiro, P. A. O.;Secolin, R.;Lopes-Cendes, I.;Cendes, F.;Balthazar, M. L. F.",2017,,10.1177/1971400917720465,0,
1808,Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume,"BACKGROUND AND PURPOSE: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory function was investigated in ALS patients and controls. METHODS: Twenty-six ALS patients without dementia and 21 healthy volunteers matched for gender, age and education level underwent comprehensive neuropsychological evaluation and T1- and T2-weighted 3 T magnetic resonance imaging scanning of the brain. Grey and white matter brain volumes were analysed using voxel-based morphometry and age related white matter changes were assessed. The most frequently abnormal memory test (<2 SD below normative data corrected for age, gender and education) was correlated with regional brain volume variations by multiple regression analyses with age, gender and total grey matter volumes as covariates. RESULTS: Immediate and delayed story recall scores were abnormal in 23% of ALS patients and correlated to bilateral hippocampus grey matter volume (r = 0.52 for both memory tests; P < 0.05; corrected for age, gender and total grey matter volume). This correlation was not found in healthy controls with similar age, education, anxiety and depression levels and white matter changes. CONCLUSIONS: Prose memory impairment is a frequent finding in this cohort and is associated with hippocampus volume in ALS patients without dementia. These findings complement previous hippocampus changes in imaging studies in ALS and suggest involvement of the hippocampus in cognitive dysfunction of ALS.",Aged;Amyotrophic Lateral Sclerosis/ pathology/ physiopathology;Atrophy/pathology;Female;Hippocampus/ pathology/ physiopathology;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/ pathology/ physiopathology;Middle Aged,"Raaphorst, J.;van Tol, M. J.;de Visser, M.;van der Kooi, A. J.;Majoie, C. B.;van den Berg, L. H.;Schmand, B.;Veltman, D. J.",2015,Mar,10.1111/ene.12615,0,
1809,Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions,"Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 +/- 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 +/- 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.","Adult;Aged;Aged, 80 and over;Apolipoprotein E4/genetics;Brain/pathology;Brain Injuries/*genetics;Cholesterol Ester Transfer Proteins/*genetics;Dementia, Vascular/*genetics;Female;Gene Frequency;Genetic Predisposition to Disease;Genotype;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;*Polymorphism, Single Nucleotide;Sequence Analysis, DNA","Qureischie, H.;Heun, R.;Popp, J.;Jessen, F.;Maier, W.;Schmitz, S.;Hentschel, F.;Kelemen, P.;Kolsch, H.",2009,Apr,10.1007/s00702-008-0180-y,0,
1810,Using computerized tomography to identify neurologic problems,"Computerized tomography (CT) scanning accurately identifies neurologic abnormalities in many elderly patients, often making it possible to differentiate symptomatic neurologic changes of normal aging from treatable pathologic states such as occult masses and cerebral infarction producing much the same symptoms. The scan also singles out patients in whom further diagnostic measures are necessary. The advantages of CT--low morbidity, noninvasiveness, and high sensitivity--far outweigh its limitations. Concomitant cerebral atrophy and metabolic imbalance do not significantly affect diagnostic accuracy. Risks are minimal, related chiefly to contrast allergy, and occasionally to anesthetics for patients who cannot remain motionless during the procedure.",aged;article;brain disease;brain tumor;case report;computer assisted tomography;dementia;female;human;male;methodology;middle aged;neurologic disease;pathology;thromboembolism,"Quisling, R.",1978,,,0,
1811,Catatonia after cerebral hypoxia: do the usual treatments apply?,"BACKGROUND: Neurologic deterioration occurring days to weeks after a cerebral hypoxic event accompanied by diffuse white matter demyelination is called delayed posthypoxic leukoencephalopathy (DPHL). Manifestations of DPHL are diverse and include dementia, gait disturbance, incontinence, pyramidal tract signs, parkinsonism, chorea, mood and thought disorders, akinetic mutism, and rarely catatonia. METHODS: We report a case of malignant catatonia in a patient diagnosed with DPHL that was refractory to electroconvulsive therapy (ECT) and review the literature on catatonia in DPHL. RESULTS: The patient was a 56-year-old woman with schizoaffective disorder who was admitted with catatonia 2 weeks after hospitalization for drug overdose and respiratory failure. Her catatonic symptoms did not respond to treatment of lorazepam, amantadine, methylphenidate, or 10 sessions of bilateral ECT at maximum energy. Repeat magnetic resonance imaging revealed extensive periventricular white matter lesions not present on admission scans, and she was diagnosed with DPHL. DISCUSSION: No treatment for DPHL has been proven to be widely effective. Hyperbaric oxygen treatments may reduce the rate of development, and symptom improvement has been reported with stimulants and other psychotropic agents. Review of literature reveals rare success with GABAergic agents for catatonia after cerebral hypoxia and no cases successfully treated with ECT. There are 7 case reports of neurologic decompensation during ECT treatment after a cerebral hypoxic event. CONCLUSION: Caution is advised when considering ECT for catatonia when delayed sequelae of cerebral hypoxia are on the differential diagnosis, as there is a dearth of evidence to support this treatment approach.",,"Quinn, D. K.;Abbott, C. C.",2014,Nov-Dec,10.1016/j.psym.2014.03.010,0,
1812,Genetically-mediated Grey and White Matter Alteration in Normal Elderly Individuals with the CLU-C Allele Gene,"BACKGROUND: Several genome-wide association studies have found that the rs11136000 polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer's disease (LOAD). However, the effects of the CLU-C/C genotype on brain structure, including gray and white matter, are not adequately understood. OBJECTIVES: We aimed to clarify the gray matter and white matter integrity changes in non-demented ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C) and the correlation with cognitive performance. METHODS: Voxel-based analysis was used to compare the differences in high-resolution structural T1 and diffusion tensor imaging data between 31 CLU-C/C and 15 non-CLU-C/C carriers in nondemented older adults. RESULTS: Compared to non-CLU-C/C carriers, CLU-C homozygotes showed a reduced gray matter concentration (GMC) in the left parahippocampal gyrus, right middle frontal and temporal middle gyri, increased GMC in the left middle frontal and right fusiform gyri and increased gray matter volume (GMV) in the left middle frontal gyrus (P < 0.001). Decreased fractional anisotropy (FA) in the sub-gyral white matter of the left external capsule and left anterior cingulate and increased FA in the sub-gyral white matter of the left temporal lobe were also found in CLU-C/C genotype carriers. Moreover, the FA value in the left external capsule correlated with several cognitive measures. CONCLUSION: Our findings provide further evidence for the CLU risk variant as a candidate gene for AD and may serve as a pre-clinical neuroimaging phenotype of late-onset AD.","0 (CLU protein, human);0 (Clusterin);Aged;Aging/ genetics/pathology;Alleles;Clusterin/ genetics;Cognition Disorders/genetics/pathology;Diffusion Tensor Imaging;Female;Genome-Wide Association Study;Genotype;Gray Matter/diagnostic imaging/ pathology;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Neuropsychological Tests;Polymorphism, Single Nucleotide/ genetics;White Matter/diagnostic imaging/ pathology","Qiu, L.;He, Y.;Tang, H.;Zhou, Y.;Wang, J.;Zhang, W.;Chen, G.;Zhao, F.;Ouyang, T.;Ju, B.;Li, Z.;Wang, L.;Zou, L.;Gong, Q.",2016,,,0,1813
1813,Genetically-Mediated Grey and White Matter Alteration in Normal Elderly Individuals with the CLU-C Allele Gene,"Several genome-wide association studies have found that the rs11136000 polymorphism of the C allele (CLU-C) is associated with the risk for developing late-onset Alzheimer's disease (LOAD). However, the effects of the CLU-C/C genotype on brain structure, including gray and white matter, are not adequately understood. OBJECTIVES: We aimed to clarify the gray matter and white matter integrity changes in non-demented ageing individuals with the AD risk gene of the rs11136000 polymorphism of the C allele (CLU-C) and the correlation with cognitive performance. METHODS: Voxel-based analysis was used to compare the differences in high-resolution structural T1 and diffusion tensor imaging data between 31 CLU-C/C and 15 non-CLU-C/C carriers in non-demented older adults. RESULTS: Compared to non-CLU-C/C carriers, CLU-C homozygotes showed a reduced gray matter concentration (GMC) in the left parahippocampal gyrus, right middle frontal and temporal middle gyri, increased GMC in the left middle frontal and right fusiform gyri and increased gray matter volume (GMV) in the left middle frontal gyrus (P < 0.001). Decreased fractional anisotropy (FA) in the sub-gyral white matter of the left external capsule and left anterior cingulate and increased FA in the sub-gyral white matter of the left temporal lobe were also found in CLU-C/C genotype carriers. Moreover, the FA value in the left external capsule correlated with several cognitive measures. CONCLUSIONS: Our findings provide further evidence for the CLU risk variant as a candidate gene for AD and may serve as a pre-clinical neuroimaging phenotype of late-onset AD.",,"Qiu, L.;He, Y.;Tang, H.;Zhou, Y.;Wang, J.;Zhang, W.;Chen, G.;Zhao, F.;Ouyang, T.;Ju, B.;Li, Z.;Wang, L.;Zou, L.;Gong, Q.",2016,Jul 3,,0,
1814,"Cerebral microbleeds, retinopathy, and dementia: The AGES-Reykjavik Study","Objective: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons. Methods: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions. Results: People with multiple (≥2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62). Conclusion: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community. © 2010 by AAN Enterprises, Inc.",,"Qiu, C.;Cotch, M. F.;Sigurdsson, S.;Jonsson, P. V.;Jonsdottir, M. K.;Sveinbjörnsdottir, S.;Eiriksdottir, G.;Klein, R.;Harris, T. B.;Van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2010,14,,0,
1815,Surface-based analysis on shape and fractional anisotropy of white matter tracts in Alzheimer's disease,"BACKGROUND: White matter disruption has been suggested as one of anatomical features associated with Alzheimer's disease (AD). Diffusion tensor imaging (DTI), which has been widely used in AD studies, obtains new insights into the white matter structure. METHODS: We introduced surface-based geometric models of the deep white matter tracts extracted from DTI, allowing the characterization of their shape variations relative to an atlas as well as fractional anisotropy (FA) variations on the atlas surface through large deformation diffeomorphic metric mapping (LDDMM). We applied it to assess local shapes and FA variations of twenty-three deep white matter tracts in 13 patients with AD and 19 healthy control subjects. RESULTS: Our results showed regionally-specific shape abnormalities and FA reduction in the cingulum tract and the sagittal stratum tract in AD, suggesting that disruption in the white matter tracts near the temporal lobe may represent the secondary consequence of the medial temporal lobe pathology in AD. Moreover, the regionally-specific patterns of FA and shape of the white matter tracts were shown to be of sufficient sensitivity to robustly differentiate patients with AD from healthy comparison controls when compared with the mean FA and volumes within the regions of the white matter tracts. Finally, greater FA or deformation abnormalities of the white matter tracts were associated with lower MMSE scores. CONCLUSION: The regionally-specific shape and FA patterns could be potential imaging markers for differentiating AD from normal aging.","Aged;Algorithms;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Brain Mapping/methods;Case-Control Studies;Diffusion Tensor Imaging/methods;Humans;Middle Aged;Models, Statistical;Principal Component Analysis;Reproducibility of Results;Surface Properties","Qiu, A.;Oishi, K.;Miller, M. I.;Lyketsos, C. G.;Mori, S.;Albert, M.",2010,,10.1371/journal.pone.0009811,0,
1816,In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods,"INTRODUCTION: Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. METHODS: VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. RESULTS: Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. CONCLUSION: This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model.","Algorithms;Alzheimer Disease/ pathology;Amyloid beta-Protein Precursor/genetics;Animals;Brain/ pathology/physiology;Diffusion Tensor Imaging/ methods;Disease Models, Animal;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Mice;Mice, Transgenic;Reproducibility of Results;Sensitivity and Specificity","Qin, Y. Y.;Li, M. W.;Zhang, S.;Zhang, Y.;Zhao, L. Y.;Lei, H.;Oishi, K.;Zhu, W. Z.",2013,Aug,10.1007/s00234-013-1195-0,0,
1817,Atlas-based deep gray matter and white matter analysis in Alzheimer's disease: diffusion abnormality and correlation with cognitive function,"Objective: To identify the diffusion alterations of deep gray matter (GM) and white matter (WM) among Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy people by atlas-based analysis (ABA), and to investigate the respective relationship with cognitive function. Methods: Twenty-one AD patients (AD group), 8 MCI patients (MCI group) and 15 normal controls (control group) were performed by conventional MRI and diffusion tensor imaging (DTI). The raw data of DTI was processed by using DTI studio software to generate the fractional anisotropy (FA) images. Then ABA was used to quantify the FA value in 58 deep GM and WM structures. The differences of FA value among three groups were compared by using one way ANOVA, with a post-hoc analysis. In AD and MCI groups, the partial correlation was further investigated between mini-mental state examination (MMSE) score and FA value in the brain regions that have significant differences between AD and MCI group or between MCI and control group. Results: Compared with control group, AD patients showed wide-spread FA decrease in most deep GM and WM regions (corrected P<0.05). The FA values of the hypothalamus, the fornix, the superior longitudinal fasciculus (SLF) and the cingulum in AD group were significantly lower than those in MCI group (corrected P<0.05). The FA value of the right splenium of corpus callosum (SCC) in MCI group was significantly lower than that in control group (MCI: 0.550±0.018 vs. Control: 0.585±0.026, P<0.05). In AD and MCI group, the FA values of the left hypothalamus, the right hypothalamus, the left cingulum, the right cingulum, and the left SLF were positively correlated with MMSE scores (r=0.502, 0.515, 0.535, 0.527, 0.512; P<0.05). No significant correlation was found between the FA value of the right SCC, the right SLF, the right fornix/stria terminalis, the right fornix and MMSE scores (P>0.05). Conclusion: Based on ABA, this study found the diffusion changes not only in the WM but also the deep GM in AD patients, but only WM diffusion disruptions in MCI group. The decreased FA value in the right SCC appeared early, but had no correlation with the cognitive impairment. The FA value in the hypothalamus, the fornix, the SLF and the cingulum decreased with the disease progression, and correlated positively with the cognition decline.",Alzheimer disease;article;atlas based analysis;brain analysis;brain fornix;brain region;cingulum (brain);clinical article;clinical assessment;clinical evaluation;cognition;comparative study;controlled study;corpus callosum;diffusion tensor imaging;fractional anisotropy;gray matter;human;hypothalamus;image analysis;mild cognitive impairment;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;physical parameters;stria terminalis;superior longitudinal fasciculus;white matter,"Qin, Y.;Zhang, S.;Guo, L.;Zhang, M.;Zhu, W.",2016,,,0,
1818,Clinical analysis of neurological involvement in acquired immunodeficiency syndrome,"Objective: To deepen the understanding of clinical features of acquired immunodeficiency syndrome (AIDS) and reduce the rate of misdiagnosis. Methods: Data of 12 patients with nervous system complications and opportunistics infection in 28 human immunodeficiency virus (HIV) infected persons and (or) AIDS patients were analysed retrospectively. The patients were admitted to our hospital from January 2007 to June 2011. Results: Among the 12 patients, there were 5 cases of HIV encephalopathy, 3 chronic meningitis, 1 symmetrical polyneuropathy, 1 acquired demyelinating peripheral neuropathy, 1 cereboral infarction and 1 myopathy. The morbidity of HIV/AIDS complicated with nervous system lesion was 42.86% (12/28). Patients had 1 or 2 kinds of opportunistic infections. The morbidity rate of viral infection was 83.33% (10/12) while cryptococcal meningitis was 25% (7/28). Conclusion: HIV infection may involve the muscle and multiple sites of nervous system. AIDS patients were often complicated with mixed infection, especially viral infection in multiple systems. The main signs and symptoms are emaciation, intermittent fever, headache, cough, cognitive deterioration and meningeal irritation sign. The presentations are complicated and may induce misdiagnosis and missed diagnosis. Cerebrospinal fluid, lung CT, head CT and (or) MRI and other accessory examinations should be performed for confirming diagnosis as soon as possible.",acquired immune deficiency syndrome;article;brain infarction;cerebrospinal fluid analysis;clinical article;clinical feature;cognitive defect;computer assisted tomography;coughing;cryptococcal meningitis;demyelinating neuropathy;diagnostic error;fever;headache;HIV associated dementia;human;Human immunodeficiency virus infection;mixed infection;morbidity;myopathy;neurologic disease;nuclear magnetic resonance imaging;opportunistic infection;peripheral neuropathy;polyneuropathy;weight reduction,"Qin, X.;Xu, Z.;Chen, Y.;Shang, T.;Xiong, J.",2011,,,0,
1819,Clinical and neuroimaging features of gliomatosis cerebri confirmed by neuropathology,"Objective: To study the clinical and neuroimaging features of gliomatosis cerebri(GC) so as to enhance the accuracy of diagnosis. Methods: The clinical manifestations and cranial MRI characteristics of 10 cases of GC confirmed by neuropathology of brain biopsy were analyzed. Results: Main clinical features of the 10 patients were not so severe and varied with headache, dizziness, dementia, aphasia, epilepsy, etc. Cranial MRI scan showed diffuse long T(2) signals in frontal lobes, temporal lobes, parietal lobes, occipital lobes bilaterally, as well as corpus collosum, thalamus, paraventricular white matter, caudate nucleus and putamen. Brain stem and cerebellum were also involved. The borders of the lesions were unclear and no obvious mass effect was found. Contrast enhancement was positive only in 3 patients after Gd-DTPA injection. The lesions were always bilateral without cystic formation or hemorrhage. DWI signals of 8 cases were in accordance with pathological grades. Cho/Cr and Cho/NAA ratio increased in all 7 cases with MRS imaging. Cho/Cr in tumor area versus normal area was 1.28 ± 0.15 vs 0.92 ± 0.17 (t=4.201, P = 0.0012, 95% CI: 0.17-0.57). The value of Cho/NAA was 3.21 ± 1.19 vs 0.61 ± 0.18 (t = 5.116, P = 0.0001, 95%",,"Qian, H. R.;Qi, X. K.;Wang, W.;Liu, J. G.;Liu, P.;Qiu, F.",2010,December,,0,
1820,Default Mode Network Connectivity and Related White Matter Disruption in Type 2 Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment,"BACKGROUND: As a risk factor for Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM) itself causes cognitive impairment and has higher prevalence of mild cognitive impairment (MCI). OBJECTIVE: The aim of this study was to explore the cognition especially the episodic memory difference, the DMN functional connectivity and DMN-related white matter integrity in patients with both T2DM and amnestic MCI (T2DM-MCI) as compared to patients with T2DM only. METHODS: Focusing especially on T2DM population, we investigated the default mode network (DMN) through resting-state functional magnetic resonance imaging among 22 elderly T2DM-MCI patients and 24 elderly T2DM patients. Including primarily the bilateral cingulum, hippocampus and uncinate fasciculus, these DMN white matter fibers were also closely associated with episodic memory and the integrity of them was also investigated using diffusion tensor imaging in 19 elderly T2DM-MCI patients and 23 elderly T2DM patients. RESULTS: Compared with the patients with T2DM, the T2DM-MCI patients performed worse in several areas of cognition besides episodic memory, and showed stronger DMN functional connectivity in the left precuneus and weaker functional connectivity in the left calcarine, as well as decreased integrity of the left cingulate bundle and bilateral uncinate fasciculus. Furthermore, a correlation analysis indicated that higher left calcarine connectivity was associated with better episodic memory performance among the overall group. CONCLUSION: Our results demonstrated that T2DM patients with comorbid amnestic MCI had abnormal functional connectivity patterns and decreased white matter integrity, which could potentially serve as AD or AD risk biomarkers for early detection of those elderly individuals with T2DM.",Type 2 diabetes mellitus;default mode network;episodic memory;functional connectivity;mild cognitive impairment;white matter integrity,"Qi, D.;Wang, A.;Chen, Y.;Chen, K.;Zhang, S.;Zhang, J.;Li, X.;Ai, L.;Zhang, Z.",2017,,,0,
1821,Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy),"BACKGROUND AND PURPOSE: Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. METHODS: We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. RESULTS: Three hundred sixty-nine patients (mean age, 51.4+/-11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P=0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P=0.02). CONCLUSIONS: The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data.",Adult;Brain Ischemia/ diagnostic imaging/epidemiology;CADASIL/ diagnostic imaging/epidemiology;Cerebral Hemorrhage/ diagnostic imaging/epidemiology;Female;Follow-Up Studies;Humans;Incidence;Magnetic Resonance Imaging/methods;Male;Microvessels/ diagnostic imaging;Middle Aged;Prospective Studies;Risk Factors;Stroke/ diagnostic imaging/epidemiology;Cadasil;cerebral microbleeds;cohort studies;ischemic stroke;survival analysis,"Puy, L.;De Guio, F.;Godin, O.;Duering, M.;Dichgans, M.;Chabriat, H.;Jouvent, E.",2017,Oct,,0,
1822,Creutzfeldt-Jakob disease: Magnetic resonance imaging findings,"Rapidly progressive dementia in an adult with findings of bilateral, symmetric high signal intensity on T2-weighted sequences and normal findings on T1-weighted sequences predominantly in the deep grey matter is suggestive of Creutzfeldt-Jakob disease (CJD). The peripheral cortex may be involved, as it was in the present case. The absence of subcortical periventricular white matter high signal intensity suggests that symmetric high signal intensities within the basal ganglia and cortical grey matter are more likely to be due to a degenerative process rather than due to ischaemia, infection or tumour.",,"Puvaneswary, M.;Floate, D.;Harper, C.",1999,1999,,0,
1823,Single-photon emission computerized tomography (SPECT) in neuropsychiatry: a review,"Cranial single-photon emission computerized tomography (SPECT or SPET) can now give regional cerebral blood flow images with a resolution approaching that of positron emission tomography (PET). In this paper, the use of high resolution SPECT neuroimaging in neuropsychiatric disorders, including Alzheimer's disease, multi-infarct dementia, Pick's disease, progressive supranuclear palsy, Korsakoff's psychosis, Creutzfeld-Jakob disease, Parkinson's disease, Huntington's disease, schizophrenia, mood disorders, obsessive-compulsive disorder, HIV infection and AIDS is reviewed. Finally, further potential research and clinical uses, based on ligand studies, are outlined.",,"Puri, B. K.;Lewis, S. W.",1992,,10.3233/ben-1992-5301,0,
1824,Paradoxical embolisation and cerebral white matter lesions in dementia,"The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle cerebral artery for 1 h. A ""significant"" v-aCS (venous-to-arterial circulation shunt indicative of PFO; > or =15 embolic signals within 12 cardiac cycles) was detected by intravenous injection of ""air in saline"" ultrasound contrast. Deep white matter hyperintensities (DWMH) and periventricular hyperintensities (PVH) were assessed using Schelten's scale. After correction for cardiovascular risk factors, both DWMH and PVH were significantly associated with the presence of a PFO in AD (beta = 0.31, p = 0.02 for DWMH, odds ratio 8.7, p = 0.011 for PVH) but not in VaD. No consistent relationship was found between SCE and WMH in AD. In VaD, the severity of DWMH was negatively correlated with SCE (beta = -0.55; p = 0.001). In conclusion, the presence of a significant venous-to-arterial shunt is associated with more severe DWMH in AD, and may play a part in the aetiology of the disorder. In addition, there is a significant negative correlation between SCE and DWMH in VaD, which supports the hypothesis that VaD may be the result of ischaemic injury, predominantly reflecting embolic aetiology.","Aged;Aged, 80 and over;Alzheimer Disease/*etiology/pathology;Brain/pathology;Dementia, Vascular/*etiology/pathology;Female;Foramen Ovale, Patent/complications;Humans;Intracranial Embolism/*complications/ultrasonography;Magnetic Resonance Imaging;Male;Middle Aged;Middle Cerebral Artery/ultrasonography;Ultrasonography, Doppler, Transcranial","Purandare, N.;Oude Voshaar, R. C.;McCollum, C.;Jackson, A.;Burns, A.",2008,Jan,10.1259/bjr/90498392,0,
1825,Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study,"OBJECTIVES: To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia. DESIGN: Observational pilot study with adjustment for potential confounders using analysis of covariance. SETTING: Secondary care old-age psychiatry services in greater Manchester, United Kingdom. PARTICIPANTS: Ninety-seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D polymorphism of the ACE genotype was associated with severity of DWMH (P = .005) but not PVH (P = .34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E epsilon4 allele. CONCLUSION: The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample.","Aged;Aged, 80 and over;Alzheimer Disease/ genetics/pathology;Apolipoprotein E4;Apolipoproteins E/genetics;Brain/ pathology;Dementia, Vascular/ genetics/pathology;Female;Genotype;Humans;Male;Peptidyl-Dipeptidase A/ genetics;Pilot Projects;Polymorphism, Genetic/ genetics","Purandare, N.;Oude Voshaar, R. C.;Davidson, Y.;Gibbons, L.;Hardicre, J.;Byrne, J.;McCollum, C.;Jackson, A.;Burns, A.;Mann, D. M.",2006,Sep,10.1111/j.1532-5415.2006.00841.x,0,
1826,Paradoxical embolization: A potential cause of cerebral damage in Alzheimer's disease?,"Background: There are considerable overlaps between vascular dementia and Alzheimer's disease (AD), with a suggestion that cerebrovascular disease (CVD) contributes to the neurodegenerative pathology of AD. Paradoxical embolization of venous emboli into the systemic circulation through a venous to arterial circulation shunt (v-aCS), the most commonly a patent foramen ovale (PFO), is known to cause cryptogenic stroke in younger people. We reviewed the potential role of paradoxical embolization in AD. Methods: A review of the literature on paradoxical embolization in neurological disorders and techniques to detect v-aCS and PFO, supplemented by data from our own studies. Results: Before our research, the role of paradoxical embolism in dementia had not been studied. The potential role of embolization in cerebral damage was highlighted by studies in patients undergoing coronary artery bypass or carotid surgery. Paradoxical embolization was found to occur in patients with cryptogenic stroke, migraine, decompression sickles and during hip surgery. The methods for detecting v-aCS or PFO had not been standardized. We found 'significant' v-aCS (equivalent to PFO) in 32% of AD patients compared with 22% of controls, but the study was not sufficiently powered to test the statistic significance of this difference. In AD, there was evidence of an association between 'significant' v-aCS and the severity of white matter hyperintensities on magnetic resonance imaging (MRI). Conclusion: Paradoxical embolization through a v-aCS may be a potentially preventable or treatable cause of CVD in AD. © 2006 W. S. Maney & Son Ltd.",,"Purandare, N.;Oude Voshaar, R. C.;Burns, A.;Velupandian, U. M.;McCollum, C.",2006,September,,0,
1827,Interrater agreement of computed tomography infarct measurement,"To determine the reliability of infarct measurements on hardcopy computed tomography (CT) images the in vivo (IV) infarct volumes of 20 CT-detected infarcts were estimated and divided into four size groups with 5 infarcts in each group: Group A, less than 0.5 ml; Group B, 0.5 to 5.0 ml; Group C, 5 to 50 ml; and Group D, more than 50 ml. Seventeen infarcts were measured once and 3 infarcts three times to the nearest 0.5 mm by each of two neurologists and two neuroradiologists using a ruler on hard-copy CT images. The longest diameter (designated AP), the greatest diameter at right angles to AP (designated LAT), and the number of slices showing the infarct were recorded and multiplied by the hard-copy minification factor to give IV dimensions. Volume (VOL) was calculated according to a previously published method. Interrater intracrass correlation coefficients for all infarcts combined were 0.98 (AP), 0.91 (LAT), and 0.97 (VOL). Using all raters' measurements for any single infarct, the difference between the largest and the smallest measurement of AP and LAT was smallest (< 6 mm IV) for Group A and largest (< 31 mm IV) for Group D. This difference was largest relative to the dimension being measured in Groups A and B, where it reached 101% of the mean of the four raters' measurements for the AP dimension being measured in Group B, and 70% of the dimension being measured in Group A. With all raters' measurements for any single infarct, the difference between the largest and smallest measurement of VOL was smallest (<: 0.5 ml) for Group A and largest (< 260 ml) for Group D. This difference was largest relative to the mean volume of the infarct being measured in Group B, where it reached 153% of the mean of the four raters' measurements for VOL and reached 11.5% of the mean of the four raters' measurements for VOL in Group A. The authors conclude that infarcts can be measured on hard-copy im ages with good interrater agreement. When infarcts with a volume smaller than 5 ml are measured, differences between raters' measurements may exceed the size of the dimensions being measured.",,"Pullicino, P.;Snyder, W.;Munschauer, F.;Pordell, R.;Greiner, F.",1996,1996,,0,
1828,Neuroimaging criteria for vascular dementia,"OBJECTIVE: To examine published imaging criteria that separate cranial computed tomographic (CT) scans into grades of increasing support for a diagnosis of vascular dementia (VaD). DESIGN: Patients were divided into 4 grades of increasing extent of vascular lesions on CT. The frequency of VaD was compared between these grades. SETTING: A university department of neurology. PATIENTS: Forty-two consecutive patients who underwent neuropsychological assessment for possible dementia and who had a CT scan performed within 6 months following any stroke causing dementia. Patients with delirium, severe aphasia, and motor and/or sensory deficits that impaired neuropsychological testing and patients with mass lesions or nonvascular white matter disease shown on CT were excluded. MAIN OUTCOME MEASURE: The National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for probable VaD. RESULTS: The frequency of VaD was greater in patients with grade 1 (7 [50%] of 14, P = .01), grade 2 (2[50%] of 4, P = .2), and grade 3(7[78%] of 9, P = .002) scans than the frequency of VaD with grade O scans (1[7%] of 15). There was a linear association of the frequencies of VaD between imaging grades (P = .0008). In a subgroup of patients with neuropsychological deficits caused by cerebrovascular disease, there was a linear association of the severity of the deficits between imaging grades (P = .007). CONCLUSIONS: We conclude that our criteria can separate CTs into increasing levels of support for a diagnosis of VaD. The extent of vascular lesions on CT reflects the severity of associated neuropsychological deficts.","Adult;Aged;Aged, 80 and over;Dementia, Vascular/ radiography;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Tomography, X-Ray Computed","Pullicino, P.;Benedict, R. H.;Capruso, D. X.;Vella, N.;Withiam-Leitch, S.;Kwen, P. L.",1996,Aug,,0,
1829,Review: Silent brain infarcts are common in the elderly general population,,C reactive protein;cholesterol;creatinine;age;aged;alcohol consumption;brain damage;brain infarction;cardiovascular disease;dementia;diabetes mellitus;diagnostic imaging;human;hypertension;image analysis;information retrieval;nuclear magnetic resonance imaging;outcome assessment;prevalence;risk factor;short survey;smoking;standardization;cerebrovascular accident;white matter,"Pullicino, P.",2008,,,0,
1830,Relationship between leuko-araiosis and blood pressure variability in the elderly,"Although leuko-araiosis is a common finding on computed tomographic (CT) scans of the brain, its pathogenesis remains uncertain. To investigate the association between blood pressure (BP) disturbances and leuko-araiosis, we retrospectively reviewed CT scans and 24-hour ambulatory blood pressure monitorings of 79 elderly patients (57 women and 22 men; mean age: 83.3 +/- 6.4 years). Of the 79 patients, 50 were demented (30 had Alzheimer's disease and 18 vascular dementia) and 29 were not demented. The leuko-araiosis score (LA score) was determined by using Rezek's scale. To evaluate short-term variation of BP, we determined (1) the variability of systolic and diastolic BPs (SBP, DBP; within-subject standard deviation of all readings over a 24-hour period), (2) the coefficient of variability (variability of BP/mean BP) and (3) the maximal variation of BP (difference between the maximum and minimum 24-hour BPs). Higher LA scores were associated with higher SBPs in 24-hour, diurnal and nocturnal periods, higher maximal variation of SBP, greater variability of SBP during 24-hour, diurnal and nocturnal periods and greater coefficient of variability of SBP during sleep. Our study suggests that elevations and short-term variations of SBP may contribute to the pathogenesis of white matter lesions in elderly persons.","Aged;Aged, 80 and over;Blood Pressure/*physiology;Blood Pressure Monitoring, Ambulatory;Circadian Rhythm/*physiology;Dementia, Vascular/*radiography;Diagnosis, Differential;Female;Humans;Male;*Tomography, X-Ray Computed","Puisieux, F.;Monaca, P.;Deplanque, D.;Delmaire, C.;di Pompeo, C.;Monaca, C.;Leys, D.;Pruvo, J. P.;Dewailly, P.",2001,,50783,0,
1831,MRI and cognitive patterns in relapsing-remitting multiple sclerosis,"We studied the relationships between magnetic resonance imaging (MRI) and the Luria-Nebraska Neuropsychological Battery (LNNB) in 64 patients with relapsing-remitting multiple sclerosis (MS). MRI films were scored according to arbitrary descriptive criteria designed to emphasize patterns of alterations. Five groups were created: group 1 and 2 had typical discrete white matter lesions, group 3 had confluent lesions, group 4 had large discrete lesions and group 5 had only few small lesions. In addition, groups 2 and 3 had evidence of parenchymal atrophy. Groups 2 and 3 were the most impaired on the LNNB, but none of these patients was actually demented. Groups 1 and 5 were globally intact in spite of very different mean age and MRI pattern. Group 4 was composed of younger subjects with a shorter disease duration; they showed mild loss of attentive and abstracting abilities. We suggest that since their MRI was showing greater signs of local biological activity their mental deficits may be a transitory condition capable of two distinct outcomes: a favorable one as in groups 1 and 5, and a slowly progressive one associated with loss of brain tissue as in groups 2 and 3.",Adolescent;Adult;Analysis of Variance;Brain/pathology;Cognition;Cognition Disorders/etiology;Disability Evaluation;Discriminant Analysis;Female;Humans;Luria-Nebraska Neuropsychological Battery;Magnetic Resonance Imaging;Male;Middle Aged;Multiple Sclerosis/complications/ diagnosis/ psychology;Psychometrics/methods;Recurrence,"Pugnetti, L.;Mendozzi, L.;Motta, A.;Cattaneo, A.;Biserni, P.;Caputo, D.;Cazzullo, C. L.;Valsecchi, F.",1993,Apr,,0,
1832,White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?,"IMPORTANCE: Current hypothetical models emphasize the importance of beta-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. OBJECTIVE: To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. DESIGN: Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). SETTING: The Alzheimer's Disease Neuroimaging Initiative public database. PARTICIPANTS: The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. MAIN OUTCOME MEASURES: Clinical AD diagnosis and WMH volume. RESULTS: Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. CONCLUSIONS AND RELEVANCE: White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/ diagnosis/ metabolism/radionuclide imaging;Amyloidosis/ etiology;Aniline Compounds;Brain Mapping;Cerebral Cortex/ pathology/radionuclide imaging;Databases, Factual/statistics & numerical data;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/pathology/radionuclide imaging;Nerve Fibers, Myelinated/ pathology;Positron-Emission Tomography;Thiazoles","Provenzano, F. A.;Muraskin, J.;Tosto, G.;Narkhede, A.;Wasserman, B. T.;Griffith, E. Y.;Guzman, V. A.;Meier, I. B.;Zimmerman, M. E.;Brickman, A. M.",2013,Apr,10.1001/jamaneurol.2013.1321,0,
1833,Comparison of cerebral blood flow and structural penumbras in relation to white matter hyperintensities: A multi-modal magnetic resonance imaging study,"Normal-appearing white matter (NAWM) surrounding WMHs is associated with decreased structural integrity and perfusion, increased risk of WMH growth, and is referred to as the WMH penumbra. Studies comparing structural and cerebral blood flow (CBF) penumbras within the same individuals are lacking, however, and would facilitate our understanding of mechanisms resulting in WM damage. This study aimed to compare both CBF and structural WMH penumbras in non-demented aging. Eighty-two elderly volunteers underwent 3T-MRI including fluid attenuated inversion recovery (FLAIR), pulsed arterial spin labeling and diffusion tensor imaging (DTI). A NAWM layer mask was generated for periventricular and deep WMHs. Mean CBF, DTI-fractional anisotropy (DTI-FA), DTI-mean diffusivity (DTI-MD) and FLAIR intensity for WMHs and its corresponding NAWM layer masks were computed and compared against its mean within total brain NAWM using mixed effects models. For both periventricular and deep WMHs, DTI-FA, DTI-MD and FLAIR intensity changes extended 2-9 mm surrounding WMHs (p </= 0.05), while CBF changes extended 13-14 mm (p </= 0.05). The CBF penumbra is more extensive than structural penumbras in relation to WMHs and includes WM tissue both with and without microstructural changes. Findings implicate CBF as a potential target for the prevention of both micro and macro structural WM damage.",Arterial spin labeling;aging;cerebral blood flow;diffusion tensor imaging;magnetic resonance imaging;vascular cognitive impairment,"Promjunyakul, N. O.;Lahna, D. L.;Kaye, J. A.;Dodge, H. H.;Erten-Lyons, D.;Rooney, W. D.;Silbert, L. C.",2016,Sep,10.1177/0271678x16651268,0,
1834,Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures,"OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.","Aged;Aged, 80 and over;Aging/*pathology/physiology;Cerebrovascular Circulation/*physiology;Female;Humans;Magnetic Resonance Imaging/*methods;Male;Spin Labels;White Matter/blood supply/*pathology;Arterial spin labeling (ASL);CASL, continuous arterial spin labeling;CBF, cerebral blood flow;Cerebral blood flow (CBF) penumbra;Cognitive aging;DWMH, deep white matter hyperintensity;M0, the initial ASL datasets;NAWM L1, normal appearing white matter layer 1;NAWM L15, normal appearing white matter layer 15;NAWM, normal appearing white matter;PASL, pulsed arterial spin labeling;PCASL, pseudo-continuous arterial spin labeling;PVWMH, periventricular white matter hyperintensity;Vascular dementia;WMH, white matter hyperintensity;White matter hyperintensity (WMH)","Promjunyakul, N.;Lahna, D.;Kaye, J. A.;Dodge, H. H.;Erten-Lyons, D.;Rooney, W. D.;Silbert, L. C.",2015,,10.1016/j.nicl.2015.04.012,0,
1835,Cerebral white matter lesions and the risk of dementia,"Objective: To study the association between white matter lesions (WML) in specific locations and the risk of dementia. Design: The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. Setting: General population. Participants: We included 1077 people aged 60 to 90 years who did not have dementia at baseline. Main Outcome Measure: Incident dementia by Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM III-R) criteria. Results: During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. Conclusion: White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.",,"Prins, N. D.;Van Dijk, E. J.;Den Heijer, T.;Vermeer, S. E.;Koudstaal, P. J.;Oudkerk, M.;Hofman, A.;Breteler, M. M. B.",2004,October,,0,
1836,"Cerebral small-vessel disease and decline in information processing speed, executive function and memory","Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.","Aged;Aged, 80 and over;Cerebral Infarction/psychology;Cerebrovascular Disorders/pathology/*psychology;Cognition Disorders/*etiology/pathology;Female;Humans;Leukoaraiosis/psychology;Magnetic Resonance Imaging/methods;Male;Memory Disorders/*etiology/pathology;Middle Aged;Neuropsychological Tests;Prospective Studies","Prins, N. D.;van Dijk, E. J.;den Heijer, T.;Vermeer, S. E.;Jolles, J.;Koudstaal, P. J.;Hofman, A.;Breteler, M. M.",2005,Sep,10.1093/brain/awh553,0,
1837,"White matter hyperintensities, cognitive impairment and dementia: an update","White matter hyperintensities (WMHs) in the brain are the consequence of cerebral small vessel disease, and can easily be detected on MRI. Over the past three decades, research has shown that the presence and extent of white matter hyperintense signals on MRI are important for clinical outcome, in terms of cognitive and functional impairment. Large, longitudinal population-based and hospital-based studies have confirmed a dose-dependent relationship between WMHs and clinical outcome, and have demonstrated a causal link between large confluent WMHs and dementia and disability. Adequate differential diagnostic assessment and management is of the utmost importance in any patient, but most notably those with incipient cognitive impairment. Novel imaging techniques such as diffusion tensor imaging might reveal subtle damage before it is visible on standard MRI. Even in Alzheimer disease, which is thought to be primarily caused by amyloid, vascular pathology, such as small vessel disease, may be of greater importance than amyloid itself in terms of influencing the disease course, especially in older individuals. Modification of risk factors for small vessel disease could be an important therapeutic goal, although evidence for effective interventions is still lacking. Here, we provide a timely Review on WMHs, including their relationship with cognitive decline and dementia.",Alzheimer disease;brain;cerebrovascular disease;cognitive defect;dementia;diagnosis;diffusion tensor imaging;disability;disease course;functional disease;hospital;human;imaging;implantable cardiac monitor;nuclear magnetic resonance imaging;patient;population;risk factor;vascular disease;white matter;amyloid,"Prins, N. D.;Scheltens, P.",2015,,10.1038/nrneurol.2015.10,0,1838
1838,"White matter hyperintensities, cognitive impairment and dementia: an update","White matter hyperintensities (WMHs) in the brain are the consequence of cerebral small vessel disease, and can easily be detected on MRI. Over the past three decades, research has shown that the presence and extent of white matter hyperintense signals on MRI are important for clinical outcome, in terms of cognitive and functional impairment. Large, longitudinal population-based and hospital-based studies have confirmed a dose-dependent relationship between WMHs and clinical outcome, and have demonstrated a causal link between large confluent WMHs and dementia and disability. Adequate differential diagnostic assessment and management is of the utmost importance in any patient, but most notably those with incipient cognitive impairment. Novel imaging techniques such as diffusion tensor imaging might reveal subtle damage before it is visible on standard MRI. Even in Alzheimer disease, which is thought to be primarily caused by amyloid, vascular pathology, such as small vessel disease, may be of greater importance than amyloid itself in terms of influencing the disease course, especially in older individuals. Modification of risk factors for small vessel disease could be an important therapeutic goal, although evidence for effective interventions is still lacking. Here, we provide a timely Review on WMHs, including their relationship with cognitive decline and dementia.",,"Prins, N. D.;Scheltens, P.",2015,,,0,
1839,Predictors of progression from mild cognitive impairment to dementia in the placebo-arm of a clinical trial population,"We studied the predictive value of cognitive performance, vascular risk factors, apolipoprotein E (APOE) genotype, and structural brain changes on MRI, on progression to dementia in post hoc analyses of 426 placebo patients (mean age 71 years; 55% women) with mild cognitive impairment (MCI) who participated in a previously published large multi-center clinical trial (Gal-Int-11). The ADAS-cog/MCI test, the New York University Paragraph Recall Test, and the Digit Symbol Coding Test were available at baseline, as were vascular risk factors and APOE genotype. Medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH) and lacunes were assessed on MRI. Over two years of follow-up, 81 patients (19%) converted to dementia, while 345 patients (81%) remained stable. Results of Cox proportional-hazards regression analysis showed that higher age, worse cognitive test performance, presence of an APOE ?4 allele, and higher MTA scores on MRI increased the risk of progression to dementia in univariate analyses. Vascular risk factors, and WMH and lacunes on MRI, were not associated with progression to dementia. Lower performance on the ADAS-cog/MCI test (HR 1.08 per point increase; 95% CI 1.06-1.10) and Delayed recall test (HR 0.76 per point increase; 95% CI 0.68-0.85), as well as higher MTA scores on MRI (HR 1.33 per point increase; 95% CI 1.00-1.77) were independent predictors of progression to dementia in a step-wise Cox proportional-hazards model with age and gender forced into the model. We conclude that global cognitive function, episodic memory performance, and MTA on MRI independently predict progression to dementia in patients with MCI.",Age Factors;Apolipoproteins E [genetics];Atrophy;Brain [pathology];Dementia [diagnosis] [genetics] [pathology];Disease Progression;Genotype;Magnetic Resonance Imaging;Mild Cognitive Impairment [diagnosis] [genetics] [pathology];Neuroimaging;Neuropsychological Tests;Proportional Hazards Models;Retrospective Studies;Risk Factors;Temporal Lobe [pathology];Humans[checkword];Sr-dementia,"Prins, N. D.;Flier, W. M.;Brashear, H. R.;Knol, D. L.;Pol, L. A.;Barkhof, F.;Scheltens, P.",2013,,10.3233/jad-122233,0,
1840,Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study,"BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are associated with AD and vascular dementia, but the relation with cognitive performance in nondemented elderly people is not known. OBJECTIVE: To examine the association of tHcy and cognitive function in the elderly, and assess whether this may be mediated by structural brain changes on MRI. METHODS: The Rotterdam Scan Study is a population-based study of 1,077 nondemented elderly. Cognitive performance was assessed, and compound scores were constructed for psychomotor speed, memory function, and global cognitive function. Cerebral infarcts, white matter lesions, and generalized brain atrophy were measured on MRI. The cross-sectional relationship between tHcy levels and neuropsychological test scores was assessed by multiple regression. RESULTS: Mean tHcy level was 11.5 micro mol/L (SD 4.1). Increasing tHcy levels were associated with lower scores for psychomotor speed, memory function, and global cognitive function, and this was largely due to the association with tHcy levels in the upper quintile (>14 micro mol/L). Adjusted differences between test scores of participants in the upper quintile as compared with the lower four quintiles of tHcy were -0.26 (95% CI: -0.37; -0.14) for psychomotor speed, -0.13 (95% CI: -0.27; 0.01) for memory function, and -0.20 (95% CI: -0.30; -0.11) for global cognitive function. These associations were not mediated by structural brain changes on MRI. CONCLUSION: Elevated tHcy levels are associated with decreased cognitive performance in nondemented elderly people, and the relation was most marked for psychomotor speed. This association was independent of structural brain changes on MRI.",Aged;Aging/*metabolism/pathology;Atrophy;Brain/pathology;*Cognition;Female;Homocysteine/*blood;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prospective Studies;Psychomotor Performance,"Prins, N. D.;Den Heijer, T.;Hofman, A.;Koudstaal, P. J.;Jolles, J.;Clarke, R.;Breteler, M. M.",2002,Nov 12,,0,
1841,Cerebral white matter lesions and the risk of dementia in the Rotterdam scan study,"Cerebral white matter lesions are thought to be involved in the etiology of dementia, but evidence from prospective studies is scarce. In the prospective population-based Rotterdam Scan Study, we studied the association between white matter lesions and dementia. We scored periventricular and subcortical white matter lesions on MRI in 1,077 older people who were non-demented at baseline. We followed participants for five years on average for incident dementia. Higher severity of periventricular white matter lesions increased the risk of dementia (adjusted hazard ratio per standard deviation 1.67, 95% CI 1.25 to 2.24), whereas the association between subcortical white matter lesions and dementia was less prominent. Periventricular white matter lesions also increased the risk of clinical Alzheimer's disease. These findings suggest that white matter lesions, especially in the periventricular region, are involved in the etiology of dementia and strengthen the notion that vascular factors are involved in Alzheimer's disease.",article;brain damage;dementia;disease association;disease severity;human;major clinical study;nuclear magnetic resonance imaging;population research;prospective study;risk assessment;risk factor;white matter,"Prins, N. D.",2005,,,0,
1842,Quantitative EEG findings in patients with subcortical vascular encephalopathy,"To characterize the neurophysiological profile of patients with Subcortical Vascular Encephalopathy (SVE) we compared the quantified electroencephalogram (qEEG) of 15 consecutive patients, demented and non-demented, with leukoaraiosis and multiple lacunar infarcts on tomographic scan and magnetic resonance investigation, with those of 30 patients with Alzheimer's disease (AD) and 30 controls. The investigation was carried out using an EEG fast Fourier transform program, and the data obtained were transformed into mean frequency (MF), calculated in the left occipital derivation, and in percent difference (PD), calculated in eight derivations. The data obtained were compared with the scores of the mini-mental state examination (MMS). The results demonstrate that the patients with SVE displayed a different qEEG pattern in comparison with AD patients and controls, with a prevalence of EEG slowing in frontal derivations, and with good correlation between PD values and MMS scores. The qEEG may detect subtle and/or early changes in patients with SVE. The use of adequate spectral parameters may give valuable data for a better classification of dementia syndromes.",adult;aged;Alzheimer disease;article;brain disease;brain infarction;controlled study;dementia;electroencephalography;female;human;major clinical study;male;nuclear magnetic resonance imaging;priority journal;quantitative diagnosis,"Primavera, A.;Novello, P.",1992,,,0,
1843,Dissociating Statistically-Determined Alzheimer's Disease/Vascular Dementia Neuropsychological Syndromes Using White and Gray Neuroradiological Parameters,"BACKGROUND: There is remarkable heterogeneity in clinical Alzheimer's disease (AD) or vascular dementia (VaD). OBJECTIVES: 1) To statistically examine neuropsychological data to determine dementia subgroups for individuals clinically diagnosed with AD or VaD and then 2) examine group differences in specific gray/white matter regions of interest. METHODS: A k-means cluster analysis requested a 3-group solution from neuropsychological data acquired from individuals diagnosed clinically with AD/VaD. MRI measures of hippocampal, caudate, ventricular, subcortical lacunar infarction, whole brain volume, and leukoaraiosis (LA) were analyzed. Three regions of LA volumes were quantified and these included the periventricular (5 mm around the ventricles), infracortical (5 mm beneath the gray matter), and deep (between periventricular and infracortical) regions. RESULTS: Cluster analysis sorted AD/VaD patients into single domain amnestic (n = 41), single-domain dysexecutive (n = 26), and multi-domain (n = 26) phenotypes. Multi-domain patients exhibited worst performance on language tests; however, multi-domain patients were equally impaired on memory tests when compared to amnestic patients. Statistically-determined groups dissociated using neuroradiological parameters: amnestic and multi-domain groups presented with smaller hippocampal volume while the dysexecutive group presented with greater deep, periventricular, and whole brain LA. Neither caudate nor lacunae volume differed by group. Caudate nucleus volume negatively correlated with total LA in the dysexecutive and multi-domain groups. CONCLUSIONS: There are at least three distinct subtypes embedded within patients diagnosed clinically with AD/VaD spectrum dementia. We encourage future research to assess a) the neuroradiological substrates underlying statistically-determined AD/VaD spectrum dementia and b) how statistical modeling can be integrated into existing diagnostic criteria.",Caudate nucleus;Philadelphia (repeatable) Verbal Learning Test;executive function;hippocampus;lacune;learning;leukoaraiosis;memory;ventricles;white matter abnormalities,"Price, C. C.;Tanner, J. J.;Schmalfuss, I. M.;Brumback, B.;Heilman, K. M.;Libon, D. J.",2015,,10.3233/jad-150407,0,
1844,Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease,"OBJECTIVE: This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson's disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. METHODS: Participants completed a neuropsychological protocol, Unified Parkinson's Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy. RESULTS: Idiopathic Parkinson's disease (n = 40; Hoehn & Yahr stages 1-3) and non-Parkinson's disease 'control' peers (n = 40) matched on demographics, general cognition, comorbidity, and imaging/blood vascular metrics. Cognitively, individuals with Parkinson's disease were significantly more impaired than controls on tests of processing speed, secondary deficits on working memory, with subtle impairments in memory, abstract reasoning, and visuoperceptual/spatial abilities. Anatomically, Parkinson's disease individuals were not statistically different in cortical gray thickness or subcortical gray volumes with the exception of the putamen. Tract Based Spatial Statistics showed reduced prefrontal fractional anisotropy for Parkinson's disease relative to controls. Within Parkinson's disease, prefrontal fractional anisotropy and caudate nucleus volume partially explained processing speed. For controls, only prefrontal white matter was a significant contributor to processing speed. There were no significant anatomical predictors of working memory for either group. CONCLUSIONS: Caudate nuclei volume and prefrontal fractional anisotropy, not frontal gray matter thickness, showed unique and combined significance for processing speed in Parkinson's disease. Findings underscore the relevance for examining gray-white matter interactions and also highlight clinical processing speed metrics as potential indicators of early cognitive impairment in PD.",,"Price, C. C.;Tanner, J.;Nguyen, P. T.;Schwab, N. A.;Mitchell, S.;Slonena, E.;Brumback, B.;Okun, M. S.;Mareci, T. H.;Bowers, D.",2016,,10.1371/journal.pone.0147332,0,
1845,MRI-leukoaraiosis thresholds and the phenotypic expression of dementia,"OBJECTIVE: To examine the concept of leukoaraiosis thresholds on working memory, visuoconstruction, memory, and language in dementia. METHODS: A consecutive series of 83 individuals with insidious onset/progressive dementia clinically diagnosed with Alzheimer disease (AD) or small vessel vascular dementia (VaD) completed neuropsychological measures assessing working memory, visuoconstruction, episodic memory, and language. A clinical MRI scan was used to quantify leukoaraiosis, total white matter, hippocampus, lacune, and intracranial volume. We performed analyses to detect the lowest level of leukoaraiosis associated with impairment on the neuropsychological measures. RESULTS: Leukoaraiosis ranged from 0.63% to 23.74% of participants' white matter. Leukoaraiosis explained a significant amount of variance in working memory performance when it involved 3% or more of the white matter with curve estimations showing the relationship to be nonlinear in nature. Greater leukoaraiosis (13%) was implicated for impairment in visuoconstruction. Relationships between leukoaraiosis, episodic memory, and language measures were linear or flat. CONCLUSIONS: Leukoaraiosis involves specific threshold points for working memory and visuoconstructional tests in AD/VaD spectrum dementia. These data underscore the need to better understand the threshold at which leukoaraiosis affects and alters the phenotypic expression in insidious onset dementia syndromes.","Aged;Aged, 80 and over;Dementia/complications/*pathology/*psychology;Hippocampus/*pathology;Humans;Language;Leukoaraiosis/complications/*pathology/*psychology;Magnetic Resonance Imaging/methods/psychology;Memory, Episodic;Memory, Short-Term;Nerve Fibers, Myelinated/pathology;Neuroimaging/methods/*psychology;Neuropsychological Tests/statistics & numerical data;Organ Size;Phenotype;Psychomotor Performance;Severity of Illness Index","Price, C. C.;Mitchell, S. M.;Brumback, B.;Tanner, J. J.;Schmalfuss, I.;Lamar, M.;Giovannetti, T.;Heilman, K. M.;Libon, D. J.",2012,Aug 21,10.1212/WNL.0b013e3182661ef6,0,
1846,Subcortical vascular dementia: integrating neuropsychological and neuroradiologic data,"BACKGROUND: Research criteria for subcortical vascular dementia are based on radiologic evidence of vascular pathology and greater impairment on tests of executive control than memory. The relationship(s) between neuroradiological evidence of subcortical vascular disease and neuropsychological impairments has not been specified. OBJECTIVE: To define these research criteria, the authors rated the severity of MRI white matter abnormalities (WMAs) and neuropsychological data from patients with dementia. METHODS: Sixty-nine outpatients who met the criteria for dementia were studied with neuropsychological tests that assessed executive (mental) control, declarative memory, visuoconstruction (clock drawing), and language (semantic category fluency). MRI-WMAs were rated using a leukoaraiosis (LA) scale (range 0 to 40). RESULTS: First, regression analyses demonstrated that neuropsychological measures accounted for 60.7% of the variance in WMA severity (47.3% of this variance attributable to executive/visuoconstructive test performance, 13.4% attributable to memory/language test performance). Second, patients were grouped according to the severity of WMAs (i.e., low, moderate, and severe white matter groups). Only patients with mild WMA (mean LA = 3.61 +/- 2.63, approximately 2.4 to 15.6% of the subcortical white matter) presented with greater impairment on memory/language tests vs executive control/visuoconstructive tests, a neuropsychological profile typically associated with Alzheimer disease. Patients with moderate WMA (mean LA = 12.76 +/- 2.49, approximately 25.6 to 38.1% of the subcortical white matter) presented with equal impairment on executive/visuoconstructional vs memory/language tests. Patients with severe WMA (mean LA = 21.76 +/- 2.97, approximately 46.9 to 62.4% of the subcortical white matter) displayed a profile of greater executive/visuoconstructional impairment relative to memory/language disabilities. CONCLUSION: A profile of equal impairment on tests of executive control and memory along with radiologic evidence involving about one-fourth of the cerebral white matter as measured by the Leukoaraiosis Scale may be sufficient for a diagnosis of subcortical vascular dementia.","Age Factors;Aged;Aged, 80 and over;Cerebral Arteries/*pathology;Cerebral Cortex/blood supply/*pathology/*physiopathology;Cognition Disorders/etiology/pathology/psychology;Dementia, Vascular/*pathology/physiopathology/*psychology;Disease Progression;Educational Status;Humans;Language Disorders/etiology/pathology/psychology;Magnetic Resonance Imaging;Memory Disorders/etiology/pathology/psychology;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Predictive Value of Tests;Statistics as Topic","Price, C. C.;Jefferson, A. L.;Merino, J. G.;Heilman, K. M.;Libon, D. J.",2005,Aug 9,10.1212/01.wnl.0000168877.06011.15,0,
1847,Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5-year study,"In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc.",adult;article;attention;brain asymmetry;brain atrophy;brain cortex;brain damage;brain region;brain size;cerebellum;controlled study;demyelinating disease;disability;disease course;disease duration;Expanded Disability Status Scale;female;follow up;gray matter;hemisphere;human;left hemisphere;longitudinal study;major clinical study;male;mental deterioration;multiple sclerosis;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;paced auditory serial addition test;priority journal;prospective study;symbol digit modalities test;verbal communication;verbal memory;visual memory;voxel based morphometry;white matter,"Preziosa, P.;Pagani, E.;Mesaros, S.;Riccitelli, G. C.;Dackovic, J.;Drulovic, J.;Filippi, M.;Rocca, M. A.",2017,,10.1002/hbm.23755,0,
1848,A novel approach of groupwise fMRI-guided tractography allowing to characterize the clinical evolution of Alzheimer's disease,"Guiding diffusion tract-based anatomy by functional magnetic resonance imaging (fMRI), we aim to investigate the relationship between structural connectivity and functional activity in the human brain. To this purpose, we introduced a novel groupwise fMRI-guided tractographic approach, that was applied on a population ranging between prodromic and moderate stages of Alzheimer's disease (AD). The study comprised of 15 subjects affected by amnestic mild cognitive impairment (aMCI), 14 diagnosed with AD and 14 elderly healthy adults who were used as controls. By creating representative (ensemble) functionally guided tracts within each group of participants, our methodology highlighted the white matter fiber connections involved in verbal fluency functions for a specific population, and hypothesized on brain compensation mechanisms that potentially counteract or reduce cognitive impairment symptoms in prodromic AD. Our hope is that this fMRI-guided tractographic approach could have potential impact in various clinical studies, while investigating white/gray matter connectivity, in both health and disease.",Adult;Aged;Alzheimer Disease/ pathology/ physiopathology;Brain/pathology/physiopathology;Brain Mapping;Case-Control Studies;Demography;Diffusion Tensor Imaging/ methods;Disease Progression;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/pathology/physiopathology;Task Performance and Analysis,"Preti, M. G.;Makris, N.;Papadimitriou, G.;Lagana, M. M.;Griffanti, L.;Clerici, M.;Nemni, R.;Westin, C. F.;Baselli, G.;Baglio, F.",2014,,10.1371/journal.pone.0092026,0,
1849,Comparison between skeleton-based and atlas-based approach in the assessment of corpus callosum damages in Mild Cognitive Impairment and Alzheimer Disease,"The damage of specific bundles in the brain white matter (WM) is currently assessed in Alzheimer Disease (AD) and amnestic Mild Cognitive Impairment (aMCI) by tractography based on diffusion tensor imaging (DTI) and the consequent evaluation of diffusion parameters in reconstructed tracts. Controversial results may be due to the use of different techniques. This work aims at comparing an atlas-based technique to compute fractional anisotropy (FA) in specific tracts with the voxelwise approach of Tract-Based Spatial Statistics (TBSS). FA was evaluated in 7 portions of the corpus callosum (CC) of 10 elderly healthy controls (HC), 10 aMCI and 10 mild AD patients with both approaches. Atlas-based tractography revealed concordant results with TBSS, displaying the same significant differences between AD and HC and no significant difference between aMCI and HC. However, as regards the AD to aMCI contrast only the atlas-based method was able to find significantly lowered FA in AD in frontal and parietal CC portions. This finding shows that a proper analysis which considers a higher number of voxels, not restricting the observation to the skeleton in the assessment of CC damages, could be useful for AD to aMCI differential diagnosis and prognosis.",Aged;Alzheimer Disease/ pathology;Anisotropy;Bone and Bones/ pathology;Case-Control Studies;Corpus Callosum/ pathology;Diffusion Tensor Imaging;Female;Humans;Male;Mild Cognitive Impairment/ pathology,"Preti, M. G.;Lagana, M. M.;Baglio, F.;Griffanti, L.;Nemni, R.;Cecconi, P.;Baselli, G.",2011,,10.1109/iembs.2011.6091924,0,
1850,Assessing corpus callosum changes in Alzheimer's disease: comparison between tract-based spatial statistics and atlas-based tractography,"Tractography based on Diffusion Tensor Imaging (DTI) represents a valuable tool for investigating brain white matter (WM) microstructure, allowing the computation of damage-related diffusion parameters such as Fractional Anisotropy (FA) in specific WM tracts. This technique appears relevant in the study of pathologies in which brain disconnection plays a major role, such as, for instance, Alzheimer's Disease (AD). Previous DTI studies have reported inconsistent results in defining WM abnormalities in AD and in its prodromal stage (i.e., amnestic Mild Cognitive Impairment; aMCI), especially when investigating the corpus callosum (CC). A reason for these inconsistencies is the use of different processing techniques, which may strongly influence the results. The aim of the current study was to compare a novel atlas-based tractography approach, that sub-divides the CC in eight portions, with Tract-Based Spatial Statistics (TBSS) when used to detect specific patterns of CC FA in AD at different clinical stages. FA data were obtained from 76 subjects (37 with mild AD, 19 with aMCI and 20 elderly healthy controls, HC) and analyzed using both methods. Consistent results were obtained for the two methods, concerning the comparisons AD vs. HC (significantly reduced FA in the whole CC of AD patients) and AD vs. aMCI (significantly reduced FA in the frontal portions of the CC in AD patients), thus identifying a relative preservation of the frontal CC regions in aMCI patients compared to AD. Conversely, the atlas-based method but not the TBSS showed the ability to detect a selective FA change in the CC parietal, left temporal and occipital regions of aMCI patients compared to HC. This finding indicates that an analysis including a higher number of voxels (with no restriction to tract skeletons) may detect characteristic pattern of FA in the CC of patients with preclinical AD, when brain atrophy is still modest.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Corpus Callosum/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Logistic Models;Male;Probability","Preti, M. G.;Baglio, F.;Lagana, M. M.;Griffanti, L.;Nemni, R.;Clerici, M.;Bozzali, M.;Baselli, G.",2012,,10.1371/journal.pone.0035856,0,
1851,Acute effect of a high nitrate diet on brain perfusion in older adults,"Aims: Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and results: In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion: These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. © 2010 Elsevier Inc. All rights reserved.",,"Presley, T. D.;Morgan, A. R.;Bechtold, E.;Clodfelter, W.;Dove, R. W.;Jennings, J. M.;Kraft, R. A.;Bruce King, S.;Laurienti, P. J.;Jack Rejeski, W.;Burdette, J. H.;Kim-Shapiro, D. B.;Miller, G. D.",2011,2011,,0,
1852,Multimodal FMRI resting-state functional connectivity in granulin mutations: the case of fronto-parietal dementia,"BACKGROUND: Monogenic dementias represent a great opportunity to trace disease progression from preclinical to symptomatic stages. Frontotemporal Dementia related to Granulin (GRN) mutations presents a specific framework of brain damage, involving fronto-temporal regions and long inter-hemispheric white matter bundles. Multimodal resting-state functional MRI (rs-fMRI) is a promising tool to carefully describe disease signature from the earliest disease phase. OBJECTIVE: To define local connectivity alterations in GRN related pathology moving from the presymptomatic (asymptomatic GRN mutation carriers) to the clinical phase of the disease (GRN- related Frontotemporal Dementia). METHODS: Thirty-one GRN Thr272fs mutation carriers (14 patients with Frontotemporal Dementia and 17 asymptomatic carriers) and 38 healthy controls were recruited. Local connectivity measures (Regional Homogeneity (ReHo), Fractional Amplitude of Low Frequency Fluctuation (fALFF) and Degree Centrality (DC)) were computed, considering age and gender as nuisance variables as well as the influence of voxel-level gray matter atrophy. RESULTS: Asymptomatic GRN carriers had selective reduced ReHo in the left parietal region and increased ReHo in frontal regions compared to healthy controls. Considering Frontotemporal Dementia patients, all measures (ReHo, fALFF and DC) were reduced in inferior parietal, frontal lobes and posterior cingulate cortex. Considering GRN mutation carriers, an inverse correlation with age in the posterior cingulate cortex, inferior parietal lobule and orbitofrontal cortex was found. CONCLUSIONS: GRN pathology is characterized by functional brain network alterations even decades before the clinical onset; they involve the parietal region primarily and then spread to the anterior regions of the brain, supporting the concept of molecular nexopathies.",Aged;Brain/metabolism/pathology;Female;Frontotemporal Dementia/*genetics/*pathology;Humans;Intercellular Signaling Peptides and Proteins/*genetics;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Mutation/genetics,"Premi, E.;Cauda, F.;Gasparotti, R.;Diano, M.;Archetti, S.;Padovani, A.;Borroni, B.",2014,,10.1371/journal.pone.0106500,0,
1853,Imaging procedures for amyotrophic lateral sclerosis and frontotemporal dementia,"On the basis of recent genetic and neuropathological findings, amyotrophic lateral sclerosis and frontotemporal dementia can be regarded as 2 manifestations of a continuous disease. Novel imaging techniques showing comparable structural and functional changes in patient's white and grey matter support this view. Pathological changes in ALS clearly extend beyond the motor areas and disturbances in white matter, characterised by functional hypo- and hyperconnective areas, are a crucial factor in this disease. Vice versa FTD is not restricted to frontal atrophy, but shows involvement of motor areas and recruitment of compensatory brain regions. This review focus on the main results, obtained from conventional imaging and modern MRI techniques in ALS and FTD such as voxel-based morphometry, diffusion tensor imaging, magnetisation transfer imaging, MR spectroscopy, and functional MRI. © Georg Thieme Verlag KG Stuttgart · New York.",,"Prell, T.;Grosskreutz, J.",2013,2013,,0,
1854,Patient populations in clinical studies of donepezil in vascular dementia,"BACKGROUND: There are difficulties in accurately defining patients with vascular dementia (VaD) and, therefore, little is known about the characteristics of this population. OBJECTIVE: To examine the population characteristics in patients with VaD enrolled in two randomized, double-blind, placebo-controlled, 24-week clinical trials of the efficacy and tolerability of the acetylcholinesterase inhibitor donepezil. METHODS: Enrolled patients had probable or possible VaD, classified according to NINDS-AIREN criteria. Patients were excluded if they had a diagnosis of Alzheimer's disease or dementia caused by other conditions not associated with the cardiovascular system. RESULTS: A total of 1,219 patients, 73% with probable VaD and 27% with possible VaD, were enrolled. Patients had a mean Hachinski score of 9.7, with memory impairment the most prominent feature of their dementia. Sixty-eight percent of patients had a history of at least one stroke and 28% of patients had a history of transient ischemic attack before dementia. In the 99% of patients who had abnormal computer-assisted tomography or magnetic resonance imaging scans, cortical and subcortical infarcts were among the lesions observed, with significant white-matter lesions also present in some patients. Seventy-three percent of patients had experienced an abrupt onset of cognitive symptoms. Vascular risk factors were prominent and included hypertension (70%), smoking (62%), and hypercholesterolemia (39%). CONCLUSIONS: The patients enrolled in these trials had probable or possible VaD; these patients exhibited a history of cerebrovascular disease and a broad range of comorbid cardiovascular conditions. The large number of patients enrolled will permit a thorough examination of the efficacy and tolerability of donepezil in VaD.","Alzheimer Disease [drug therapy];Brain [blood supply] [pathology] [radiography];Dementia, Vascular [diagnosis] [drug therapy] [epidemiology];Double-Blind Method;Indans [therapeutic use];Ischemic Attack, Transient [epidemiology];Magnetic Resonance Imaging;Piperidines [therapeutic use];Population Surveillance [methods];Psychometrics [methods];Severity of Illness Index;Tomography, X-Ray Computed;Treatment Outcome;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];adult;aged;Alzheimer disease/di [Diagnosis];cardiovascular disease;cerebrovascular disease/di [Diagnosis];cerebrovascular disease/dt [Drug Therapy];cerebrovascular disease/ep [Epidemiology];cigarette smoking;clinical trial;comorbidity;computer assisted tomography;conference paper;controlled clinical trial;controlled study;dementia/di [Diagnosis];dementia/dt [Drug Therapy];dementia/ep [Epidemiology];disease association;disease severity;double blind procedure;drug efficacy;drug safety;female;Hachinski score;human;hypercholesterolemia;hypertension;major clinical study;male;Mini Mental State Examination;multiinfarct dementia/di [Diagnosis];multiinfarct dementia/dt [Drug Therapy];multiinfarct dementia/ep [Epidemiology];nuclear magnetic resonance imaging;psychometry;randomized controlled trial;rating scale;risk factor;scoring system;side effect/si [Side Effect];treatment outcome;cholinesterase inhibitor/ae [Adverse Drug Reaction];cholinesterase inhibitor/ct [Clinical Trial];cholinesterase inhibitor/dt [Drug Therapy];donepezil/ae [Adverse Drug Reaction];donepezil/ct [Clinical Trial];donepezil/dt [Drug Therapy];placebo","Pratt, R. D.",2003,,10.1017/s1041610203009190,0,
1855,Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia,"There is increasing evidence to suggest that patients with vascular dementia (VaD) exhibit a cholinergic deficit. These patients may therefore benefit from treatment with cholinesterase (ChE) inhibitors such as donepezil. However, there are difficulties in accurately defining patients with VaD. Clinical trials to assess the efficacy and tolerability of donepezil in patients with VaD have been completed. National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria were used to establish inclusion and exclusion criteria: evidence of dementia (impaired memory and two other cognitive domains), and evidence of cerebrovascular disease (CVD) from neuroimaging and physical examination and a possible or probable relationship between dementia and CVD were required for enrollment. Patients with a diagnosis of Alzheimer's disease (AD) or dementia caused by other conditions not associated with the cardiovascular system (e.g., MS, chronic infections, hypothyroidism) were excluded. These criteria ensured that only patients with probable or possible VaD were enrolled. Enrolled patients had a mean Hachinski score of 9.7, with memory impairment the most prominent feature of their dementia. Sixty percent of patients had a history of at least one stroke and 18% of patients had a history of transient ischemic attack (TIA) pre-dementia. Cortical and subcortical infarcts were among the lesions observed on computer-assisted tomography and magnetic resonance imaging scans with significant white matter lesions also present in some patients. Placebo-treated patients demonstrated stable cognitive and global function over the 24 weeks of the study. These observations suggest that the patients enrolled in these trials have a broad range of CVD, and are different from those enrolled in AD trials.","Brain [pathology];Cerebrovascular Circulation [physiology];Cognition [physiology];Cohort Studies;Dementia, Vascular [drug therapy] [pathology] [psychology];Disease Progression;Double-Blind Method;Indans [therapeutic use];Neuropsychological Tests;Nootropic Agents [therapeutic use];Piperidines [therapeutic use];Psychometrics;Research Design;Risk Factors;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia","Pratt, R. D.",2002,,,0,
1856,Adult-onset leukoencephalopathy with vanishing white matter presenting with dementia,We report on a case of dementia and extensive cerebral white matter abnormalities seen on magnetic resonance-images which meet the criteria for leukoencephalopathy with vanishing white matter. This is an inherited condition that was first thought to occur only in children. Our patient shows that vanishing white matter should be considered in adult patients with early-onset dementia and extensive white matter changes seen on magnetic resonance images.,,"Prass, K.;Bruandck, W.;Schroandder, N. W. J.;Bender, A.;Prass, M.;Wolf, T.;Van Der Knaap, M. S.;Zschenderlein, R.",2001,2001,,0,
1857,"Constipation, renovascular hypertension, and posterior reversible encephalopathy syndrome (PRES)","Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity characterized by variable associations of headaches, encephalopathy, seizures, vomiting, visual disturbance, and focal neurological signs. Neuroimaging shows cerebral edema of different patterns, classically involving the parieto-occipital white matter. PRES has been associated with several conditions predominantly hypertension, eclampsia, and immunosuppressive therapy. However, constipation has not been previously described in association with the development of PRES. In this report, we describe an 11-year-old child with history of severe functional constipation who developed PRES, as a consequence of renovascular hypertension from severe fecal impaction. Both hypertension and neurologic dysfunction resolved after resolution of fecal impaction. Conclusion: Severe functional constipation is a previously unrecognized cause of severe acute hypertension, resulting in life-threatening neurologic dysfunction. We highlight this unrecognized complication of severe functional constipation with fecal impaction that is potentially preventable if managed appropriately.What is Known:• Posterior reversible encephalopathy syndrome (PRES) is a life-threatening disorder• PRES has been associated with multiple conditions, including hypertension and immunosuppressive therapyWhat is New:• Constipation with severe fecal impaction may cause severe renovascular hypertension and PRES• Severe functional constipation is a previously unrecognized cause of severe symptomatic hypertension that could result in acute brain dysfunction, such as PRES",amlodipine;diatrizoate;enalapril;enema;macrogol;nicardipine;abdominal distension;abdominal radiography;abdominal tenderness;article;brain dysfunction;child;chronic constipation;clinical article;continuous infusion;drug substitution;drug withdrawal;electroencephalogram;elevated blood pressure;feces impaction;gaze;heart left ventricle mass;human;human tissue;hydronephrosis;male;mental deterioration;nasogastric tube;neuroimaging;nuclear magnetic resonance imaging;patient compliance;positive end expiratory pressure;posterior reversible encephalopathy syndrome;priority journal;renovascular hypertension;respiratory distress;school child;sinus rhythm;small intestine obstruction;speech disorder;tachycardia;tachypnea;visual disorder;white matter,"Prasad, M.;Wetzler, G.;Holtmann, J.;Dapul, H.;Kupferman, J. C.",2016,,,0,
1858,White matter disease independently predicts progression from mild cognitive impairment to Alzheimer's disease in a clinic cohort,"BACKGROUND: The contribution of vascular pathology to the rate of progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) remains unclear. OBJECTIVE: To ascertain the relative roles of cerebral white matter disease and medial temporal atrophy (MTA) in predicting progression from MCI to AD. METHODS: MCI patients with baseline MRI and >/=18 months of longitudinal follow-up were evaluated. DSM-IV-TR criteria were used to diagnose conversion to dementia. MTA and white matter hyperintensity (WMH) were quantified using the Scheltens scale and modified Fazekas scale. RESULTS: Of a total of 171 MCI patients, 79 patients with baseline MRI and longitudinal follow-up were studied. Twenty-three MCI patients who progressed to dementia (MCI-P) were identified corresponding to a 19.4% annual risk of conversion. In MCI-P patients, the mean Mini-Mental State Examination and Montreal Cognitive Assessment decline was 1.3 and 2.9 points, respectively. MTA, periventricular WMH and deep subcortical WMH were significantly greater in the MCI-P cohort. WMH was found to predict MCI-P with an odds ratio of 7.69 (p = 0.03). CONCLUSION: MTA and deep subcortical WMH independently predict conversion from MCI to AD. Optimization of vascular risk factors among patients with MCI can potentially reduce the conversion from MCI to AD.","Aged;Alzheimer Disease/*pathology/*psychology;Brain/*pathology;Cohort Studies;Databases, Factual;Diagnostic and Statistical Manual of Mental Disorders;Disease Progression;Female;Humans;Leukoencephalopathies/*pathology/*psychology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/*pathology/*psychology;Neuropsychological Tests;Predictive Value of Tests;Retrospective Studies;Risk Factors","Prasad, K.;Wiryasaputra, L.;Ng, A.;Kandiah, N.",2011,,10.1159/000330019,0,
1859,CADASIL and ALS: A link?,"We report the case of a 66-year-old female who presented with dysarthria and dysphonia. Brain MRI abnormalities showed confluent white matter lesions and subcortical lacunar infarcts, suggesting cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), confirmed by the presence of a heterozygous mutation in the Notch3 gene. Clinical signs and course were consistent with amyotrophic lateral sclerosis (ALS) as was the electromyo-graphic pattern. The possible pathogenic role for a mutation in the Notch3 gene is discussed considering recent data on hypoxia in the pathophysiology of ALS. © 2010 Informa UK Ltd.",Notch3 receptor;aged;amyotrophic lateral sclerosis;artery disease;article;autosomal dominant inheritance;CADASIL;case report;clinical feature;disease association;disease course;dysarthria;dysphonia;electromyography;female;gene mutation;human;neuroimaging;nuclear magnetic resonance imaging;pathophysiology;priority journal;white matter,"Praline, J.;Limousin, N.;Vourc'H, P.;Pallix, M.;Debiais, S.;Guennoc, A. M.;Andres, C. R.;Corcia, P.",2010,,,0,
1860,White matter foci in asymptomatic patients [12],,adult;aged;aging;brain disease;brain ischemia;clinical trial;dementia;human;hypertension;letter;migraine;multiple sclerosis;nuclear magnetic resonance imaging;priority journal;volunteer;white matter,"Prager, J. M.;Haughton, V.",1994,,,0,
1861,Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model,Publisher: Abstract available from the publisher. Dut,App/ps1;Alzheimer's disease;Magnetic resonance imaging;Magnetization transfer contrast imaging;White matter,"Praet, J.;Bigot, C.;Orije, J.;Naeyaert, M.;Shah, D.;Mai, Z.;Guns, P. J.;Van der Linden, A.;Verhoye, M.",2016,,10.1016/j.nicl.2016.06.014,0,
1862,Recurrent transient global amnesia as presenting symptoms of CADASIL,"Despite transient global amnesia is considered unusual in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and causal relation is still unclear, this report suggests to consider CADASIL in those patients with recurrent transient global amnesia, especially when MRI shows multifocal hyperintensities affecting the cerebral white matter or when it is followed by cognitive decline.",Cadasil;NOTCH3 gene mutation;cognitive impairment;dementia;leukoaraiosis;microbleeds;transient global amnesia,"Pradotto, L.;Orsi, L.;Mencarelli, M.;Caglio, M.;Lauro, D.;Milesi, A.;Di Blasio, A.;Mauro, A.",2016,Nov,,0,
1863,A new NOTCH3 mutation presenting as primary intracerebral haemorrhage,"Primary intracerebral haemorrhages (PICH) are defined as haemorrhages within the brain parenchyma in the absence of readily identifiable causes. CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary vascular disease and its mainly clinical manifestations are early-onset infarcts. Spontaneous lobar haematomas are a rare occurrence. We report a very unusual presentation of CADASIL in a 65 year-old man carrying a new NOTCH3 mutation. The clinical onset of the disease was related to an intracerebral haematoma following colon surgery and causing a delirium. In brief, our report suggests that CADASIL must be considered in patient with PICH. © 2011 Elsevier B.V. All rights reserved.",genomic DNA;low molecular weight heparin;Notch3 receptor;aged;article;brain hematoma;brain hemorrhage;CADASIL;case report;clinical feature;colon cancer;colon surgery;computer assisted tomography;delirium;episodic memory;gene mutation;genetic analysis;genetic screening;human;human tissue;male;microscopy;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;polymerase chain reaction;priority journal;rare disease;skin test,"Pradotto, L.;Orsi, L.;Daniele, D.;Caroppo, P.;Lauro, D.;Milesi, A.;Sellitti, L.;Mauro, A.",2012,,,0,
1864,Sporadic vascular dementia as clinical presentation of a new missense mutation within exon 7 of NOTCH3 gene,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic disease characterized by ischemic stroke with early onset, migraine, seizures, and vascular dementia. CADASIL is associated with mutations within NOCT3 gene, mainly clustered in exons 3 and 4. We report a case of CADASIL presenting progressive subcortical dementia in the sixth decade. Neither family history, nor acute ischemic events were present. MRI findings were typical for CADASIL. NOTCH3 analysis disclosed a new missense mutation within exon 7, leading to the substitution of cysteine 366 with a tryptophan (Cys366Trp). Our finding suggests CADASIL diagnosis must be considered in patients with vascular dementia also in absence of stroke-like events and of family history.","CADASIL/*genetics/pathology;Cysteine/*genetics;DNA Mutational Analysis;Exons/*genetics;Female;Humans;Magnetic Resonance Imaging/methods;Middle Aged;*Mutation, Missense;Receptors, Notch/*genetics;Tryptophan/*genetics","Pradotto, L.;Azan, G.;Doriguzzi, C.;Valentini, C.;Mauro, A.",2008,Aug 15,10.1016/j.jns.2008.04.015,0,
1865,A multi-time-point modality-agnostic patch-based method for lesion filling in multiple sclerosis,"Multiple sclerosis lesions influence the process of image analysis, leading to tissue segmentation problems and biased morphometric estimates. Existing techniques try to reduce this bias by filling all lesions as normal-appearing white matter on T1-weighted images, considering each time-point separately. However, due to lesion segmentation errors and the presence of structures adjacent to the lesions, such as the ventricles and deep grey matter nuclei, filling all lesions with white matter-like intensities introduces errors and artefacts. In this paper, we present a novel lesion filling strategy inspired by in-painting techniques used in computer graphics applications for image completion. The proposed technique uses a five-dimensional (5D), patch-based (multi-modality and multi-time-point), Non-Local Means algorithm that fills lesions with the most plausible texture. We demonstrate that this strategy introduces less bias, fewer artefacts and spurious edges than the current, publicly available techniques. The proposed method is modality-agnostic and can be applied to multiple time-points simultaneously. In addition, it preserves anatomical structures and signal-to-noise characteristics even when the lesions are neighbouring grey matter or cerebrospinal fluid, and avoids excess of blurring or rasterisation due to the choice of the segmentation plane, shape of the lesions, and their size and/or location.",adult;article;brain size;cerebrospinal fluid level;controlled study;disease severity;five dimensional imaging;gray matter;human;image analysis;image quality;imaging and display;major clinical study;middle aged;multiple sclerosis;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;signal noise ratio;systematic error;white matter,"Prados, F.;Cardoso, M. J.;Kanber, B.;Ciccarelli, O.;Kapoor, R.;Gandini Wheeler-Kingshott, C. A. M.;Ourselin, S.",2016,,,0,
1866,Image evaluation of HIV encephalopathy: A multimodal approach using quantitative MR techniques,"Introduction: A multimodal approach of the human immunodeficiency virus (HIV) encephalopathy using quantitative magnetic resonance (MR) techniques can demonstrate brain changes not detectable only with conventional magnetic resonance imaging (MRI). The aim of this study was to compare conventional MRI and MR quantitative techniques, such as magnetic resonance spectroscopy (MRS) and relaxometry and to determine whether quantitative techniques are more sensitive than conventional imaging for brain changes caused by HIV infection. Methods: We studied prospectively nine HIV positive children (mean age 6 years, from 5 to 8 years old) and nine controls (mean age 7.3 years; from 3 to 10 years), using MRS and relaxometry. Examinations were carried on 1.5-T equipment. Results: HIV-positive patients presented with only minor findings and all control patients had normal conventional MR findings. MRS findings showed an increase in choline to creatine (CHO/CRE) ratios bilaterally in both frontal gray and white matter, in the left parietal white matter, and in total CHO/CRE ratio. In contrast, N-acetylaspartate to creatine (NAA/CRE) ratios did not present with any significant difference between both groups. Relaxometry showed significant bilateral abnormalities, with lengthening of the relaxation time in HIV positive in many regions. Conclusion: Conventional MRI is not sensitive for early brain changes caused by HIV infection. Quantitative techniques such as MRS and relaxometry appear as valuable tools in the diagnosis of these early changes. Therefore, a multimodal quantitative study can be useful in demonstrating and understanding the physiopathology of the disease. © 2011 Springer-Verlag.",,"Prado, P. T. C.;Escorsi-Rosset, S.;Cervi, M. C.;Santos, A. C.",2011,November,,0,
1867,White matter disease correlates with lexical retrieval deficits in primary progressive aphasia,"Objective: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval. Methods: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients. Results: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA. Conclusion: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval. © 2013 Powers, McMillan, Brun, Yushkevich, Zhang, Gee and Grossman.",adult;aged;article;clinical article;cluster analysis;controlled study;corpus callosum;diffusion weighted imaging;female;fluency disorder;fractional anisotropy;human;information retrieval;logopenic variant primary progressive aphasia;male;nuclear magnetic resonance imaging;phenotype;primary progressive aphasia;semantic variant primary progressive aphasia;uncinate fasciculus;white matter lesion,"Powers, J. P.;McMillan, C. T.;Brun, C. C.;Yushkevich, P. A.;Zhang, H.;Gee, J. C.;Grossman, M.",2013,,10.3389/fneur.2013.00212,0,
1868,White matter disease correlates with lexical retrieval deficits in primary progressive aphasia,"OBJECTIVE: To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval. METHODS: We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients. RESULTS: We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA. CONCLUSION: SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.",,"Powers, J. P.;McMillan, C. T.;Brun, C. C.;Yushkevich, P. A.;Zhang, H.;Gee, J. C.;Grossman, M.",2013,,10.3389/fneur.2013.00212,0,1867
1869,White matter disease contributes to apathy and disinhibition in behavioral variant frontotemporal dementia,"OBJECTIVE: To relate changes in fractional anisotropy associated with behavioral variant frontotemporal dementia to measures of apathy and disinhibition. BACKGROUND: Apathy and disinhibition are the 2 most common behavioral features of behavioral variant frontotemporal dementia, and these symptoms are associated with accelerated patient decline and caregiver stress. However, little is known about how white matter disease contributes to these symptoms. METHODS: We collected neuropsychiatric data, volumetric magnetic resonance imaging, and diffusion-weighted imaging in 11 patients who met published criteria for behavioral variant frontotemporal dementia and had an autopsy-validated cerebrospinal fluid profile consistent with frontotemporal lobar degeneration. We also collected imaging data on 34 healthy seniors for analyses defining regions of disease in the patients. We calculated and analyzed fractional anisotropy with a white matter tract-specific method. This approach uses anatomically guided data reduction to increase sensitivity, and localizes results within canonically defined tracts. We used nonparametric, cluster-based statistical analysis to relate fractional anisotropy to neuropsychiatric measures of apathy and disinhibition. RESULTS: The patients with behavioral variant frontotemporal dementia had widespread reductions in fractional anisotropy in anterior portions of frontal and temporal white matter, compared to the controls. Fractional anisotropy correlated with apathy in the left uncinate fasciculus and with disinhibition in the right corona radiata. CONCLUSIONS: In patients with behavioral variant frontotemporal dementia, apathy and disinhibition are associated with distinct regions of white matter disease. The implicated fiber tracts likely support frontotemporal networks that are involved in goal-directed behavior.",Aged;Apathy;Behavioral Symptoms/etiology;Diffusion Magnetic Resonance Imaging;Female;Frontotemporal Dementia/pathology/ psychology;Frontotemporal Lobar Degeneration/pathology/ psychology;Humans;Inhibition (Psychology);Leukoencephalopathies/pathology/ psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology,"Powers, J. P.;Massimo, L.;McMillan, C. T.;Yushkevich, P. A.;Zhang, H.;Gee, J. C.;Grossman, M.",2014,Dec,10.1097/wnn.0000000000000044,0,
1870,A novel leukoencephalopathy associated with tau deposits primarily in white matter glia,"A 79-year-old woman had a 10-year history of dementia, initially presenting as non-fluent aphasia. Magnetic resonance imaging showed frontal atrophy (left greater than right) and hyperintense foci within white matter. Neuropathologically, there was severe frontal atrophy due to cortical neuronal loss with spongy change and to an even greater loss of white matter that contained prominent eosinophilic deposits. The deposits were immunoreactive for phosphorylated tau, non-reactive for Aβ and α-synuclein and equivocally or weakly reactive for ubiquitin. They stained with the Gallyas, Bielschowsky, and Bodian techniques. Ultrastructural examination revealed the deposits to be composed of straight filaments with a diameter of approximately 10 nm, primarily in white matter glia. Moderate loss of neurons in substantia nigra and numerous argyrophilic threads in gray and particularly white matter were noted. The precise relationship between this disorder and other frontotemporal degenerations/tauopathies, as well as the pathogenetic basis of the leukoencephalopathy, remains to be determined.",,"Powers, J. M.;Byrne, N. P.;Ito, M.;Takao, M.;Yankopoulou, D.;Spillantini, M. G.;Ghetti, B.",2003,2,,0,
1871,Midlife and late-life vascular risk factors and white matter microstructural integrity: The atherosclerosis risk in communities neurocognitive study,"Background- Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity. Methods and Results- We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity. Conclusions- Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life.",antidiabetic agent;antilipemic agent;cholesterol;glucose;high density lipoprotein cholesterol;low density lipoprotein cholesterol;triacylglycerol;adult;article;blood pressure measurement;brain atherosclerosis;cardiovascular risk;controlled study;dementia;diabetes mellitus;diastolic blood pressure;diffusion tensor imaging;female;fractional anisotropy;human;hypercholesterolemia;hyperlipidemia;hypertension;leukoencephalopathy;longitudinal study;major clinical study;male;mild cognitive impairment;neuroimaging;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;priority journal;risk factor;systolic blood pressure;white matter injury,"Power, M. C.;Tingle, J. V.;Reid, R. I.;Huang, J.;Sharrett, A. R.;Coresh, J.;Griswold, M.;Kantarci, K.;Jack, C. R.;Knopman, D.;Gottesman, R. F.;Mosley, T. H.",2017,,10.1161/jaha.117.005608,0,
1872,Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier,"The cause of acquired immunodeficiency syndrome (AIDS) dementia, which is a frequent late manifestation of human immunodeficiency virus (HIV) infection, is unknown but radiological and pathological studies have implicated alterations in subcortical white matter. To investigate the pathological basis of these white matter abnormalities, we performed an immunocytochemical and histological analysis of subcortical white matter from AIDS patients with and without dementia, from pre-AIDS patients (asymptomatic HIV-seropositive patients), and from HIV-seronegative control subjects. Reduced intensity of Luxol fast blue staining, designated ""diffuse myelin pallor,"" was detected in 8 of 15 AIDS dementia patients, 3 of 13 AIDS nondemented patients, and none of the pre-AIDS patients (n = 2) or control subjects (n = 9). In contrast to Luxol fast blue staining, sections stained immunocytochemically for myelin proteins did not show decreased staining intensities in regions of diffuse myelin pallor. In addition, neither demyelinated axons nor active demyelination were detected in light and electron micrographs of subcortical white matter from brains of patients with AIDS dementia. An increase in the number of perivascular macrophages and hypertrophy of astrocytes and microglia occurred in brain sections from HIV-infected patients. These changes were not specific to dementia or regions of diffuse myelin pallor and they occurred in both gray and white matter. In contrast to the lack of myelin pathology in AIDS dementia brains, significant accumulations of serum proteins in white matter glia were detected in the brains of 12 of 12 patients with AIDS dementia and 6 of 12 AIDS patients without dementia. Serum protein-immunopositive cortical neurons were detected in the frontal cortex of 11 of 12 patients with AIDS dementia and 3 of 12 nondemented AIDS patients. Seronegative control subjects showed minimal serum protein immunoreactivity in both cortex and white matter. We conclude therefore that alterations in the blood-brain barrier and not demyelination contribute to the development of AIDS dementia.",AIDS Dementia Complex/*pathology/*physiopathology;Acquired Immunodeficiency Syndrome/*pathology;Adult;Autopsy;*Blood-Brain Barrier;Brain/*blood supply/*pathology;Glial Fibrillary Acidic Protein/analysis;HIV Infections/*pathology/physiopathology;HIV Seropositivity/pathology;HLA-DR Antigens/analysis;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Middle Aged;Myelin Basic Protein/analysis,"Power, C.;Kong, P. A.;Crawford, T. O.;Wesselingh, S.;Glass, J. D.;McArthur, J. C.;Trapp, B. D.",1993,Sep,10.1002/ana.410340307,0,
1873,The effect of sex and handedness on white matter anisotropy: A diffusion tensor magnetic resonance imaging study,"Diffusion tensor magnetic resonance imaging provides a way of assessing the asymmetry of white matter (WM) connectivity, the degree of anisotropic diffusion within a given voxel being a marker of coherently bundled myelinated fibers. Voxel-based statistical analysis was performed on fractional anisotropy (FA) images of 42 right- and 40 left-handers, to assess differences in underlying WM anisotropy and FA asymmetry across the whole brain. Right-handers show greater anisotropy than left-handers in the uncinate fasciculus (UF) within the limbic lobe, and WM underlying prefrontal cortex, medial and inferior frontal gyri. Significantly greater leftward FA asymmetry in cerebellum posterior lobe is seen in left- than right-handers, and males show significantly greater rightward (right-greater-than-left) FA asymmetry in regions of middle occipital lobe, medial temporal gyrus, and a region of the superior longitudinal fasciculus underlying the supramarginal gyrus. Leftward (left-greater-than-right) anisotropy is found in regions of the arcuate fasciculus (AF), UF, and WM underlying pars triangularis in both handedness groups, with right-handers alone showing additional leftward FA asymmetry along the length of the superior temporal gyrus. Overall results indicate that although both handedness groups show anisotropy in similar WM regions, greater anisotropy is observed in right-handers compared with left-handers. The largest differences in FA asymmetry are found between males and females, suggesting a greater effect of sex than handedness on FA asymmetry. © 2012 IBRO.",,"Powell, J. L.;Parkes, L.;Kemp, G. J.;Sluming, V.;Barrick, T. R.;García-Fiñana, M.",2012,5,,0,
1874,Frontal white matter integrity in adults with Down syndrome with and without dementia,"Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS.",Adult;Anisotropy;Dementia/etiology/ pathology/psychology;Diffusion Tensor Imaging;Down Syndrome/complications/ pathology/psychology;Female;Frontal Lobe/ pathology;Humans;Male;Middle Aged;Neuroimaging;Neuropsychological Tests,"Powell, D.;Caban-Holt, A.;Jicha, G.;Robertson, W.;Davis, R.;Gold, B. T.;Schmitt, F. A.;Head, E.",2014,Jul,10.1016/j.neurobiolaging.2014.01.137,0,
1875,Convex third ventricle: A possible sign for dementia using MRI,"The shape and thickness of the third ventricles were studied with magnetic resonance imaging in 46 patients under evaluation for memory impairment. We compared this population with 23 subjects imaged for other reasons. The study group consisted of patients with diagnoses of probable dementia of the Alzheimer's type (DAT; 35.6%), multi-infarct dementia (MID; 22.2%), depression (8.9%), alcoholic dementia (6.7%), other dementias (OD; 13.2%) and no dementia (6.7%). Within the study group, there were no significant differences across diagnostic categories for duration of symptoms or level of education. Patients with DAT were, however, more impaired than others (Mini-Mental State Examination scores: DAT 14.6 [±8.2] versus MID 17.4 [±6.2] versus OD 21.2 [±6.4]). Demented subjects were more likely than nondemented individuals to have a convex third ventricle and greater wall separation. The results suggest that the shape of the third ventricle may correlate with dementia. Possibly, the dorsal medial nucleus of the thalamus is involved in the dementia.",,"Powell, A. L.;Mezrich, R. S.;Coyne, A. C.;Loesberg, A.;Keller, I.",1993,1993,,0,
1876,White matter connectivity reflects clinical and cognitive status in Huntington's disease,"OBJECTIVE: To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. METHOD: Diffusion tensor imaging (DTI) data were acquired from 35 pre-HD, 36 symp-HD, and 35 controls. Structural connectivity was mapped between 40 brain regions of interest using tractography. Between-group differences in structural connectivity were identified using network based statistics. Radial diffusivity (RD) and fractional anisotropy (FA) were compared in the white matter tracts from aberrant networks. RD values in aberrant tracts were correlated with clinical severity, and cognitive and motor performance. RESULTS: A network connecting putamen with prefrontal and motor cortex demonstrated significantly reduced tractography streamlines in pre-HD. Symp-HD individuals showed reduced streamlines in a network connecting prefrontal, motor, and parietal cortices with both caudate and putamen. The symp-HD group, compared to controls and pre-HD, showed both increased RD and decreased FA in the fronto-parietal and caudate-paracentral tracts and increased RD in the putamen-prefrontal and putamen-motor tracts. The pre-HDclose, compared to controls, showed increased RD in the putamen-prefrontal and fronto-parietal tracts. In the pre-HD group, significant negative correlations were observed between SDMT and Stroop performance and RD in the bilateral putamen-prefrontal tract. In the symp-HD group, RD in the fronto-parietal tract was significantly positively correlated with UHDRS motor scores and significantly negatively correlated with performance on SDMT and Stroop tasks. CONCLUSIONS: We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.","Adult;Aged;Anisotropy;Brain/ pathology;Brain Mapping;Cognition Disorders/ etiology;Corpus Striatum/pathology;Diffusion Tensor Imaging;Female;Humans;Huntington Disease/ complications/ pathology;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Severity of Illness Index;Young Adult","Poudel, G. R.;Stout, J. C.;Dominguez, D. J.;Salmon, L.;Churchyard, A.;Chua, P.;Georgiou-Karistianis, N.;Egan, G. F.",2014,May,10.1016/j.nbd.2014.01.013,0,
1877,Longitudinal change in white matter microstructure in Huntington's disease: The IMAGE-HD study,"OBJECTIVE: To quantify 18-month changes in white matter microstructure in premanifest (pre-HD) and symptomatic Huntington's disease (symp-HD). To investigate baseline clinical, cognitive and motor symptoms that are predictive of white matter microstructural change over 18months. METHOD: Diffusion tensor imaging (DTI) data were analyzed for 28 pre-HD, 25 symp-HD, and 27 controls scanned at baseline and after 18months. Unbiased tract-based spatial statistics (TBSS) methods were used to identify longitudinal changes in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) of white matter. Stepwise linear regression models were used to identify baseline clinical, cognitive, and motor measures that are predictive of longitudinal diffusion changes. RESULTS: Symp-HD compared to controls showed 18-month reductions in FA in the corpus callosum and cingulum white matter. Symp-HD compared to pre-HD showed increased RD in the corpus callosum and striatal projection pathways. FA in the body, genu, and splenium of the corpus callosum was significantly associated with a baseline clinical motor measure (Unified Huntington's Disease Rating Scale: total motor scores: UHDRS-TMS) across both HD groups. This measure was also the only independent predictor of longitudinal decline in FA in all parts of the corpus callosum across both HD groups. CONCLUSIONS: We provide direct evidence of longitudinal decline in white matter microstructure in symp-HD. Although pre-HD did not show longitudinal change, clinical symptoms and motor function predicted white matter microstructural changes for all gene positive subjects. These findings suggest that loss of axonal integrity is an early hallmark of neurodegenerative changes which are clinically relevant.","Adult;Australia;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Huntington Disease/ pathology;Image Processing, Computer-Assisted;Linear Models;Longitudinal Studies;Male;Middle Aged;Prodromal Symptoms;Psychomotor Performance;Stroop Test;White Matter/ pathology","Poudel, G. R.;Stout, J. C.;Dominguez, D. J.;Churchyard, A.;Chua, P.;Egan, G. F.;Georgiou-Karistianis, N.",2015,Feb,10.1016/j.nbd.2014.12.009,0,
1878,Mitochondrial myopathy and leukoencephalopathy in twins of different sexes,"Two 30-year old twins, one male, the other female, were followed up for 20 years for predominantly proximal muscular deficit without increase of muscle enzymes. The lactic acid level was elevated at rest and further increased during exercise. Muscle biopsy revealed mitochondrial abnormalities. Encephalopathy was also present. The female patient had been treated, at the age of 10 years, for myoclonic attacks which regressed when she was over 18 years. None of the two patients had dementia. CT and MRI showed very extensive and symmetrical lesions of the white matter which did not involve the basal ganglia. These two cases are interesting on three scores: (1) clinically, the woman exhibited symptoms of the MELAS syndrome (without cerebral vascular accidents) and symptoms of the MERRF syndrome, which suggests the existence of borderline cases; (2) genetically, our cases were in favour of a so-called ""maternal"" heredity (boys are affected in all cases): here both sexes were involved but the phenotype varied; (3) biochemically, we found no enzyme activity deficit likely to explain the clinical features. The significance of a selective increase of cytochrome c oxidase in both mother and daughter is unclear.",adult;article;brain disease;case report;computer assisted tomography;dizygotic twins;genetics;human;male;muscle disease;myoclonus epilepsy;nuclear magnetic resonance imaging;pathology;radiography;twins,"Pou Serradell, A.;Corominas, J.;Vilaseca, M. A.;Briones, P.",1991,,,0,
1879,Molecular and clinical findings in a family with dentatorubral-pallidoluysian atrophy,"Herein we describe the molecular and clinical findings in a North American Caucasian family with dentatorubral-pallidoluysian atrophy (DRPLA). These patients all presented with an autosomal dominant neurodegenerative disorder characterized by a variable combination of clinical symptoms including seizures, ataxia, dementia, choreiform movements, mental retardation, and psychiatric disease. Neuroradiologic findings in the index case revealed deep subcortical white matter changes on magnetic resonance imaging. Prior to referral, the family carried a diagnosis of Huntington's disease (HD). Subsequent direct molecular testing for HD failed to identify the HD expansion mutation in affected individuals. Molecular testing for DRPLA, however, demonstrated the presence of the recently characterized DRPLA expansion mutation in all affected individuals. The size of the expansion correlated with the age of onset of clinical symptoms. As DRPLA has rarely been reported in North American and European populations, the molecular confirmation of DRPLA in this family provides support for the hypothesis that DRPLA may not be as geographically restricted as once thought.","Adolescent;Adult;Athetosis/ genetics/pathology;Chorea/ genetics/pathology;Epilepsies, Myoclonic/ genetics/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Pedigree;Syndrome","Potter, N. T.;Meyer, M. A.;Zimmerman, A. W.;Eisenstadt, M. L.;Anderson, I. J.",1995,Feb,10.1002/ana.410370220,0,
1880,Enlarged perivascular spaces and cerebral small vessel disease,"BACKGROUND AND AIMS: Enlarged perivascular spaces (also known as Virchow-Robin spaces) on T2-weighted brain magnetic resonance imaging are common, but their etiology, and specificity to small vessel as opposed to general cerebrovascular disease or ageing, is unclear. We tested the association between enlarged perivascular spaces and ischemic stroke subtype, other markers of small vessel disease, and common vascular risk factors. METHODS: We prospectively recruited patients with acute stroke, diagnosed and subtyped by a stroke physician using clinical features and brain magnetic resonance imaging. A neuroradiologist rated basal ganglia and centrum semiovale enlarged perivascular spaces on a five-point scale, white matter lesions, recent and old infarcts, and cerebral atrophy. We assessed associations between basal ganglia-, centrum semiovale- and total (combined basal ganglia and centrum semiovale) enlarged perivascular spaces, stroke subtype, white matter lesions, atrophy, and vascular risk factors. RESULTS: Among 298 patients (mean age 68 years), after adjusting for vascular risk factors and white matter lesions, basal ganglia-enlarged perivascular spaces were associated with increasing age (P = 0.001), centrum semiovale-enlarged perivascular spaces (P < 0.001), cerebral atrophy (P = 0.03), and lacunar stroke subtype (P = 0.04). Centrum semiovale-enlarged perivascular spaces were associated mainly with basal ganglia-enlarged perivascular spaces. Total enlarged perivascular spaces were associated with increasing age (P = 0.01), deep white matter lesions (P = 0.005), and previous stroke (P = 0.006). CONCLUSIONS: Enlarged perivascular spaces are associated with age, lacunar stroke subtype and white matter lesions and should be considered as another magnetic resonance imaging marker of cerebral small vessel disease. Further evaluation of enlarged perivascular spaces in studies of ageing, stroke, and dementia is needed to determine their pathophysiological importance.",,"Potter, G. M.;Doubal, F. N.;Jackson, C. A.;Chappell, F. M.;Sudlow, C. L.;Dennis, M. S.;Wardlaw, J. M.",2015,Apr,10.1111/ijs.12054,0,
1881,Asymptomatic and neurologically symptomatic HIV-seropositive individuals: prospective evaluation with cranial MR imaging,"As part of a prospective multidisciplinary study of individuals seropositive for the human immunodeficiency virus (HIV), cranial magnetic resonance (MR) imaging was performed on 119 HIV-seropositive subjects (95 asymptomatic, 24 symptomatic) and the results were correlated with clinical data. MR images regarded as positive included those showing atrophy and/or white matter lesions. On the basis of these criteria, 96 subjects had normal MR images and 23 had abnormal images. Results of chi 2 analysis revealed a statistically significant difference between the asymptomatic group (12 of 95 [13%] with abnormal scans) and the symptomatic group (11 of 24 [46%] with abnormal scans) (P = .001). In the asymptomatic group, positive MR images showed fewer, smaller, and/or less extensive abnormalities. The researchers conclude that (a) MR imaging can show indirect evidence of HIV infection early in the disease, but abnormalities will be minor and seen only in a small minority of neurologically asymptomatic subjects; (b) the appearance of clinically recognizable neurologic disease correlates with the MR imaging findings of increasingly severe brain atrophy and white matter lesions; and (c) in some HIV-seropositive subjects, despite neurologic disease, MR images can remain normal. Results indicate that routine screening with cranial MR imaging of neurologically asymptomatic HIV-seropositive individuals would likely result in a low yield of positive findings.",AIDS Dementia Complex/ diagnosis/epidemiology;Adult;Atrophy;Brain/ pathology;Female;HIV Seropositivity/ pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Prospective Studies;Time Factors,"Post, M. J.;Berger, J. R.;Quencer, R. M.",1991,Jan,10.1148/radiology.178.1.1984291,0,
1882,"CADASIL: A case with clinical, radiological, histological and genetic diagnoses","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease. The onset of clinical symptoms occurs with migraine with aura, transient ischemic attacks, recurrent subcortical ischemic infarcts, neuropsychiatric changes reaching subcortical dementia. Brain magnetic resonance images show multiple deep cerebral infarcts in white matter and basal ganglia and diffuse leukoencephalopathy. Neuropathologic hallmark consists of deposition of small electron dense granular patches related to the basement membrane of vascular smooth muscle cells with degeneration of smooth muscle cells and media and luminal obliteration. Recently, the genetic characteristics of this disorder have been reported. Missense mutations in notch3 gene localized in chromosome 19 are involved in its pathogenesis. Only three families from Spain have been reported. Here we describe a patient with typical clinical symptoms, neuroimaging and pathology of CADASIL. C406T (Arg11OCys) mutation in notch3 gene was found. We comment on the clinical symptoms of different members of the patient's family.",,"Posada, I. J.;García-Morales, I.;Martínez, M. A.;Hoenicka, J.;Bermejo, F.",2003,May,,0,
1883,"Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands","OBJECTIVE: To assess the clinical presentation and course of the AIDS dementia complex (ADC). DESIGN: Retrospective study of a consecutive series of symptomatic HIV-1-infected patients [Centers for Disease Control and Prevention (CDC) stages IVA, B, C and D] evaluated for neurological symptoms between 1982 and 1992. SETTING: An academic referral centre for AIDS. PATIENTS: A total of 536 symptomatic HIV-1-infected patients evaluated for neurological symptoms between 1982 and 1992. INTERVENTIONS: Zidovudine treatment, which was introduced in The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (CDC stages IVA, B, C and D). MAIN OUTCOME MEASURES: Diagnosis of ADC and CD4 cell count, clinical features, neuropsychological abnormalities, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid (CSF) findings and course in patients with ADC. RESULTS: ADC was diagnosed in 40 out of 536 (7.5%) immunosuppressed, neurologically symptomatic HIV-1-infected patients in CDC stage IV, and was the AIDS-defining illness in six. The mean CD4 cell count of the 40 patients with ADC was 109 x 10(6)/l. Neuropsychological abnormalities in 15 out of 17 patients tested were in accordance with subcortical dementia. On CT scan of the brain, 70% showed no or only mild cortical atrophy. MRI was more sensitive than CT scan for detecting white matter abnormalities (73 versus 35%; P = 0.02). CSF examination showed mononuclear pleocytosis in 25%, protein level increase in 55%, and HIV-1 p24 core protein in 38% (13 out of 34). The mean survival was 6.7 months in the 40 ADC patients, but 4 months in 20 patients who had never used zidovudine, compared with 14.8 months in 10 patients who started zidovudine after they were classified as having ADC (P < 0.001). Three of these 10 patients improved remarkably, and two slightly, after starting zidovudine. ADC developed after discontinuation of zidovudine in nine patients. Only one patient developed ADC while receiving 600 mg zidovudine. CONCLUSIONS: MRI is more sensitive than CT for detecting white matter abnormalities. To date, there is no specific or sensitive CSF marker for ADC. Zidovudine may improve symptoms and prolong survival in patients with ADC, which rarely developed with continued zidovudine use in our study.","AIDS Dementia Complex/ diagnosis/drug therapy/epidemiology;Adult;Cerebrospinal Fluid/chemistry/cytology/microbiology;Female;Follow-Up Studies;HIV Infections/drug therapy/epidemiology;Hiv-1;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Netherlands/epidemiology;Retrospective Studies;Time Factors;Tomography, X-Ray Computed;Zidovudine/therapeutic use","Portegies, P.;Enting, R. H.;de Gans, J.;Algra, P. R.;Derix, M. M.;Lange, J. M.;Goudsmit, J.",1993,May,,0,
1884,Thalamic dementia due to infarct of the left thalamus and genum of the right internal capsule,"Introduction and objectives. Thalamic dementia is the clinical consequence of a disorder of both thalami. It is generally secondary to bilateral paramedial thalamic infarcts due to disorders of small blood vessels or cardioembolism. We report a case of dementia of acute onset involving the left thalamus and the genum of the right internal capsule. Clinical case. A 33 year old man, HIV positive, category B2, admitted to hospital for tuberculous meningitis presented with the acute onset of somnolence, followed by marked bradypsychism, personality changes, marked disorder of executive explicit memory without associated praxic, gnosic or language disorders. Ocular motility remained normal. There was left central facial paralysis with inverse emotive-voluntary dissociation. The other cranial nerves were normal. There was left hemiparesia with extensor plantar reflex. No other alterations. Cerebral MR imaging was compatible with paramedial infarcts of the left thalamus and genum of the right internal capsule. Conclusions. Thalamic dementia generally occurs in bilateral paramedian thalamic disorders. There are cases of disorders of executive memory secondary to infarcts of the genum of the internal capsule due to interruption of the thalamotemporal pathways and a contralateral paramedial thalamic lesion.",,"Porta-Etessam, J.;Martínez-Salio, A.;Berbel, A.;Benito-León, J.;García-Muñoz, A.;Kesler, P.;Mateo, S.",2001,2001,,0,
1885,Elevation in plasma Abeta42 in geriatric depression: a pilot study,"Elevated plasma amyloid beta 1-42 (Abeta42) level has been linked to increased risk for incident AD in cognitively-intact elderly. However, plasma Abeta levels in individuals with late-life depression (LLMD), especially those with a late age of onset of first depressive episode, who are at a particularly increased risk for Alzheimer's disease, have not been studied. We compared plasma Abeta in 47 elderly with LLMD with 35 controls and examined its relationships to age of onset of first depressive episode, antidepressant treatment (paroxetine or nortriptyline), and indices of platelet activation (platelet factor 4 and beta-thromboglobulin) and brain abnormalities. Results indicated that plasma Abeta42 levels and the Abeta42/40 ratio were elevated in the LLMD group relative to controls in the overall group analyses and in the age- and gender-matched groups. MRI data indicated that higher Abeta42/40 ratio was associated with greater severity of total white matter hyperintensity burden in LLMD. Plasma Abeta levels in LLMD were not influenced by age of onset of first depressive episode or antidepressant treatment and were not related to indices of platelet activation. Our preliminary results suggest that increased plasma Abeta42 and Abeta42/40 ratio are present in geriatric depression, and future studies should be done to confirm these findings and to determine their relationship to cognitive decline and brain abnormalities associated with LLMD.","Aged;Aged, 80 and over;Amyloid beta-Peptides/*blood;Antidepressive Agents/therapeutic use;Brain/pathology;Depressive Disorder, Major/*blood/drug therapy/pathology;Female;Humans;Male;Middle Aged;Peptide Fragments/*blood;Pilot Projects;Platelet Activation","Pomara, N.;Doraiswamy, P. M.;Willoughby, L. M.;Roth, A. E.;Mulsant, B. H.;Sidtis, J. J.;Mehta, P. D.;Reynolds, C. F., 3rd;Pollock, B. G.",2006,Mar,10.1007/s11064-005-9029-z,0,
1886,Cerebral microbleeds in cerebrovascular and neurodegenerative diseases with cognitive impairment,"Objective. To study a role of cerebral microbleeds (CMB) in the diagnosis of main cerebrovascular and neurodegenerative diseases with cognitive impairment. Material and methods. CMB were studied in 120 patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and vascular dementia using 1.5T MRI in T2 * gradient echo. An impact of CMB on cognitive functions and the relationship with signs of vascular and neurodegenerative lesions of the brain were studied as well. The neuropsychological battery included Montreal Cognitive Assessment scale (MoCA), Addenbrooke’s Cognitive Examination (ACE-R), Clock Drawing Test, fluency test and the visual memory test (SCT). Results: CMB were identified in more than one third of patients with neurodegenerative or cerebrovascular disease. With regard to disease, they were detected preferably in cortical or subcortical areas, respectively. This result can be used in the differential diagnosis. Single subcortical CMB accompanied by a smaller number of lacunae and less severe leukoaraiosis were identified in 48% of patients with DLB. In AD with additional features of DLB and cerebrovascular disease, CMB were more common (60%) that was a predictor of mixed pathology. Conclusion. Leukoaraiosis, if accompanied by CMB, has a great clinical significance in neurodegenerative and cerebrovascular diseases with cognitive impairment. CMB is a marker of severe cognitive impairment and predictor of mixed pathology in the cortical-subcortical localization of CMB and corresponding neuropsychological profile.",Alzheimer disease;article;brain atrophy;brain hemorrhage;cerebrovascular disease;cognitive defect;controlled oral word association test;degenerative disease;diffuse Lewy body disease;human;leukoaraiosis;major clinical study;Montreal cognitive assessment;neuropsychological test;nuclear magnetic resonance imaging;visual memory;white matter lesion,"Polyakova, Т А;Levin, О S.",2016,,10.17116/jnevro20161166219-27,0,
1887,Cerebral Microbleeds in Cerebrovascular and Neurodegenerative Diseases with Cognitive Impairments,"Objectives. To identify the significance of cerebral microbleeds (CMB) in the diagnosis of the main cerebrovascular and neurodegenerative diseases with cognitive impairments (CI). Materials and methods. MRI scans (1.5 T, T2* regime, gradient echo) were performed in 120 patients with Alzheimer’s disease (AD), Lewy body dementia (LBD), and vascular dementia to study CMB, their influence on the state of cognitive functions, and links with signs of vascular and neurodegenerative brain lesions. Neuropsychological studies were performed using the Montreal and Addenbrooke scales, including assessment of speech activity, the clock drawing test, and the pictures test. Results and discussion. CMB were detected in more than 1/3 patients with neurodegenerative and cerebrovascular pathologies; cortical CMB were mostly seen in neurodegenerative pathology and subcortical in cerebrovascular pathology, and these locations can be used for differential diagnosis. Single subcortical CMB were seen in 48% of patients with LBD, and these were accompanied by smaller numbers of lacunar infarcts and a lower severity of leukoaraiosis. In AD with additional signs of LBD and cerebrovascular disease, CMB was encountered more frequently (60%) and was a criterion for mixed pathology. Conclusions. Leukoaraiosis has great clinical significance in neurodegenerative and cerebrovascular diseases with CI, if accompanied by CMB. The presence of CMB is a marker for severe CI and a predictor for mixed pathology in CMB located cortically-subcortical and the corresponding neuropsychological profile.",Addenbrook scale;aged;Alzheimer disease;anatomical variation;article;brain atrophy;brain cortex;brain hemorrhage;clock drawing test;cognitive function test;differential diagnosis;diffuse Lewy body disease;disease severity;human;lacunar stroke;leukoaraiosis;major clinical study;mental disease assessment;Montreal cognitive assessment;multiinfarct dementia;nuclear magnetic resonance imaging;pictures test;speech test,"Polyakova, T. A.;Levin, O. S.",2017,,10.1007/s11055-017-0515-y,0,
1888,Neuroimaging and molecular biomarkers of dementia,"Development of laboratory diagnosis and neuroimaging revealed a number of biomarkers for in vivo diagnosis of the most common forms of dementia (Alzheimer’s disease, Lewy body dementia and vascular dementia). Currently, the highest diagnostic sensitivity and specificity of molecular biomarkers in the cerebrospinal fluid are detected for Alzheimer’s disease. At the same time, the changes according to the magnetic resonance imaging are more prognostically significant for future cognitive decline than cerebrospinal fluid biomarkers. Cerebral microbleeds are an available adjuvant diagnostic marker, which increases the diagnostic value of leukoaraiosis that suggests the development of cerebral amyloid angiopathy or hypertensive microangiopathy, especially in cases of mixed pathology and severe cognitive deficits.",biological marker;Alzheimer disease;article;brain hemorrhage;cerebrospinal fluid;cognitive defect;dementia;diagnostic value;diffuse Lewy body disease;human;leukoaraiosis;microangiopathy;multiinfarct dementia;neuroimaging;nuclear magnetic resonance imaging;prognosis;sensitivity and specificity;vascular amyloidosis,"Polyakova, T. A.;Arablinsky, A. V.",2017,,10.17116/jnevro20171176216-22,0,
1889,The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort,"BACKGROUND: Choline is the precursor to the neurotransmitter acetylcholine. Loss of cholinergic neurons is associated with impaired cognitive function, particularly memory loss and Alzheimer disease (AD). Brain atrophy and white-matter hyperintensity (WMH) are also associated with impaired cognitive function and AD. OBJECTIVE: The objective was to determine whether a relation exists between dietary choline intake, cognitive function, and brain morphology in a large, nondemented community-based cohort. DESIGN: A dementia-free cohort of 1391 subjects (744 women, 647 men; age range: 36-83 y; mean +/- SD age: 60.9 +/- 9.29 y) from the Framingham Offspring population completed a food-frequency questionnaire administered from 1991 to 1995 (exam 5; remote intake) and from 1998 to 2001 (exam 7; concurrent intake). Participants underwent neuropsychological evaluation and brain MRI at exam 7. Four neuropsychological factors were constructed: verbal memory (VM), visual memory (VsM), verbal learning, and executive function. MRI measures included WMH volume (WMHV). RESULTS: Performance on the VM and VsM factors was better with higher concurrent choline intake in multivariable-adjusted models for VM (average change in neuropsychological factor per 1-unit change in choline = 0.60; 95% CI: 0.29, 0.91; P < 0.01) and VsM (0.66; 95% CI: 0.19, 1.13; P < 0.01). Remote choline intake was inversely related to log-transformed WMHV (average change in log WMHV per 1-unit change in choline = -0.05; 95% CI: -0.10, -0.01; P = 0.02). Furthermore, an inverse association was observed between remote higher choline intake and presence of large WMVH (OR: 0.56; 95% CI: 0.34, 0.92; P = 0.01). CONCLUSION: In this community-based population of nondemented individuals, higher concurrent choline intake was related to better cognitive performance, whereas higher remote choline intake was associated with little to no WMHV.","Adult;Aged;Aged, 80 and over;Brain/anatomy & histology/*drug effects;Choline/*pharmacology;Cognition/*drug effects;Cognition Disorders/*etiology/prevention & control;Cohort Studies;*Diet;Diet Surveys;Executive Function/*drug effects;Female;Humans;Magnetic Resonance Imaging;Male;Memory/*drug effects;Middle Aged;Multivariate Analysis;Surveys and Questionnaires","Poly, C.;Massaro, J. M.;Seshadri, S.;Wolf, P. A.;Cho, E.;Krall, E.;Jacques, P. F.;Au, R.",2011,Dec,10.3945/ajcn.110.008938,0,
1890,Frontal lobe white matter hyperintensities and neurofibrillary pathology in the oldest old,"Background: Current studies suggest an interaction between vascular mechanisms and neurodegenerative processes that leads to late-onset Alzheimer disease (AD). We tested whether AD pathology was associated with white matter hyperintensities (WMH) or cerebral infarcts in the oldest old individuals. Methods: Brains from 132 subjects over 85 years old, who came to autopsy from the Vantaa 85+ population-based cohort, were scanned by postmortem MRI and examined for neuropathologic changes. Coronal images were analyzed to determine the degree of frontal and parietal periventricular WMH (PVWMH) and deep WMH (DWMH) and cerebral infarcts. Neuropathologic variables included Consortium to Establish a Registry for Alzheimer's Disease scores for neuritic plaques and Braak staging among subjects in 5 groups: normal aging (NA), borderline with insufficient AD pathology, AD, AD plus other pathology, and other primary degenerative diseases. Results: Frontal DWMH were detected in >50% of the sample. Both frontal PVWMH and DWMH were significantly more extensive in the AD group compared to the NA group or the",,"Polvikoski, T. M.;Van Straaten, E. C. W.;Barkhof, F.;Sulkava, R.;Aronen, H. J.;Niinistö, L.;Oinas, M.;Scheltens, P.;Erkinjuntti, T.;Kalaria, R. N.",2010,7,,0,
1891,"The relationship between plasma aβ levels, cognitive function and brain volumetrics: Sydney memory and ageing study","Objectives: Determine whether (1) a relationship exists between plasma amyloid-β (Aβ)1-40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Aβ peptide levels differ between apolipoprotein E (APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aβ levels. Methods: Subjects with aMCI (n=89) and normal cognition (n=126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer’s disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were as-sessed on 19 cognitive measures and were APOE ε4 genotyped. Plasma levels of Aβ1-40 and 1-42 were quantified using ELISA. Results: Wave1 plasma levels of Aβ peptides and Aβ1−42/1-40 ratio were lower in aMCI and AD, and Aβ1−42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyper-intensities. The relationships of Aβ1-40 and Aβ1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aβ1−42 and the ratio measure. Conclusion: Plasma Aβ levels and the Aβ1−42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Aβ1-40 and Aβ1-42 in ε4 carriers and non-carriers. These data support the Aβ sink model of AD pathology, and suggest that plasma Aβ measures may serve as biomarkers of AD.",amyloid beta protein[1-40];amyloid beta protein[1-42];apolipoprotein E4;aged;aging;Alzheimer disease;article;brain size;cognition;controlled study;female;genotype;human;major clinical study;male;memory;mild cognitive impairment;nuclear magnetic resonance imaging;priority journal;receiver operating characteristic;volumetry;white matter,"Poljak, A.;Crawford, J. D.;Smythe, G. A.;Brodaty, H.;Slavin, M. J.;Kochan, N. A.;Trollor, J. N.;Wen, W.;Mather, K. A.;Assareh, A. A.;Ng, P. C.;Sachdev, P. S.",2016,,,0,
1892,"The Relationship Between Plasma Abeta Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study","OBJECTIVES: Determine whether (1) a relationship exists between plasma amyloid-beta (Abeta)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly individuals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Abeta peptide levels differ between apolipoprotein E (APOE) epsilon4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Abeta levels. METHODS: Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old individuals; 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE epsilon4 genotyped. Plasma levels of Abeta1-40 and 1-42 were quantified using ELISA. RESULTS: Wave1 plasma levels of Abeta peptides and Abeta1-42/1-40 ratio were lower in aMCI and AD, and Abeta1-42 was positively associated with global cognition and hippocampal volume and negatively with white matter hyperintensities. The relationships of Abeta1-40 and Abeta1-42 were predominantly observed in epsilon4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Abeta1-42 and the ratio measure. CONCLUSION: Plasma Abeta levels and the Abeta1-42/1-40 ratio are related to cognition and hippocampal volumes, with differential associations of Abeta1-40 and Abeta1-42 in epsilon4 carriers and non-carriers. These data support the Abeta sink model of AD pathology, and suggest that plasma Abeta measures may serve as biomarkers of AD.",,"Poljak, A.;Crawford, J. D.;Smythe, G. A.;Brodaty, H.;Slavin, M. J.;Kochan, N. A.;Trollor, J. N.;Wen, W.;Mather, K. A.;Assareh, A. A.;Ng, P. C.;Sachdev, P. S.",2016,,,0,
1893,Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation,"BACKGROUND: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. METHODS: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. RESULTS: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. CONCLUSIONS: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended.",,"Polidori, M. C.;Calistri, V.;Mainero, C.;Tinelli, E.;Aceti, A.;Pontico, M.;Tardioli, S.;Santini, M.;Fiorelli, M.;Panico, M. A.;Speziale, F.;Caramia, M. D.;Schulz, R. J.;Caramia, F.",2015,,,0,
1894,Cerebral microbleeds in early Alzheimer's disease,"We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Addenbrooke's Cognitive Examination (ACE-R), Cambridge Cognitive Examination battery (CAMCOG) (Part 3), Clock Drawing Test, fluency test and the visual memory test (SCT). CSF was examined for standard parameters such as tau, phosphorylated tau, amyloid-beta 1-40 and 42 and Qalbumin, in accordance with established protocols and genotype. In 61 patients (45 %), at least 1 CMB was found. Most of the CMBs were described in the amnestic profile (67 %). In 86 % of the cases, multiple CMB were observed. The ratio of Abeta1-40/42 in non-amnestic patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). A notable difference in the albumin ratio as an indicator of the BBB was observed between groups with and without CMB. In the CMP-positive group, the E2 genotype was observed more frequently, and the E4 genotype less frequently, than in the CMB-negative group. Based on the cerebrospinal fluid-serum albumin ratio, we were able to show that patients with CMB present several features of BBB dysfunction. According to logistic regression, the predictive factors for CMB in patients with cognitive decline were age, WMHs score and albumin ratio. We found a significant reduction in the Abeta-amyloid ratio in the non-amnestic profile group with CMB (particularly in the cortical region) in comparison to those without CMB. While this is an interesting finding, its significance needs to be assessed in a prospective follow-up.","0 (Amyloid beta-Peptides);0 (Apolipoproteins E);0 (Peptide Fragments);0 (amyloid beta-protein (11-42));0 (tau Proteins);Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/ complications/diagnostic imaging;Amyloid beta-Peptides/cerebrospinal fluid;Apolipoproteins E/genetics;Cerebral Hemorrhage/cerebrospinal fluid/diagnostic imaging/ etiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Peptide Fragments/cerebrospinal fluid;tau Proteins/cerebrospinal fluid;Alzheimer disease;Blood-brain barrier damage;Cerebral microbleeds;Mild cognitive impairment;White matter lesions","Poliakova, T.;Levin, O.;Arablinskiy, A.;Vasenina, E.;Zerr, I.",2016,Oct,,0,1895
1895,Cerebral microbleeds in early Alzheimer's disease,"We hypothesize that cerebral microbleeds (CMB) in patients with different neuropsychological profiles (amnestic or non-amnestic) and MRI features of vascular damage could provide important information on the underlying pathological process in early Alzheimer's disease. The study was performed at two trial sites. We studied 136 outpatients with cognitive decline. MRI was performed using a magnetic field of 1.5 and 3 T. Neuropsychological assessment included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Addenbrooke's Cognitive Examination (ACE-R), Cambridge Cognitive Examination battery (CAMCOG) (Part 3), Clock Drawing Test, fluency test and the visual memory test (SCT). CSF was examined for standard parameters such as tau, phosphorylated tau, amyloid-beta 1-40 and 42 and Qalbumin, in accordance with established protocols and genotype. In 61 patients (45 %), at least 1 CMB was found. Most of the CMBs were described in the amnestic profile (67 %). In 86 % of the cases, multiple CMB were observed. The ratio of Abeta1-40/42 in non-amnestic patients with CMB was significantly lower (mean 0.6) than in patients without CMB (mean 1.2). A notable difference in the albumin ratio as an indicator of the BBB was observed between groups with and without CMB. In the CMP-positive group, the E2 genotype was observed more frequently, and the E4 genotype less frequently, than in the CMB-negative group. Based on the cerebrospinal fluid-serum albumin ratio, we were able to show that patients with CMB present several features of BBB dysfunction. According to logistic regression, the predictive factors for CMB in patients with cognitive decline were age, WMHs score and albumin ratio. We found a significant reduction in the Abeta-amyloid ratio in the non-amnestic profile group with CMB (particularly in the cortical region) in comparison to those without CMB. While this is an interesting finding, its significance needs to be assessed in a prospective follow-up.",Alzheimer disease;Blood-brain barrier damage;Cerebral microbleeds;Magnetic resonance imaging;Mild cognitive impairment;White matter lesions,"Poliakova, T.;Levin, O.;Arablinskiy, A.;Vasenina, E.;Zerr, I.",2016,Jul 7,10.1007/s00415-016-8220-2,0,
1896,Magnetic resonance imaging predictors of cognition in mild cognitive impairment,"OBJECTIVES: To describe magnetic resonance imaging characteristics in a large sample of subjects with mild cognitive impairment (MCI) and to investigate associations between these characteristics and cognition. DESIGN: Cohort study. SETTING: Baseline data of a randomized, double-blind, placebo-controlled clinical trial of galantamine in MCI. PATIENTS: Included in the study were 896 subjects with MCI (age [mean +/- SD], 70 +/- 9 years; 54% women) with available clinical and magnetic resonance imaging data. MAIN OUTCOME MEASURES: Neuropsychology: Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, assessing global cognition; delayed recall on the New York University Paragraph Recall Test, assessing episodic memory; and Digit Symbol Substitution Test, assessing executive function. Neuroimaging: Medial Temporal Lobe Atrophy (MTA) Rating Scale (0-4) and Age-Related White Matter Changes Scale (0-30), assessing white matter hyperintensities (WMHs); and lacune counts. RESULTS: Median MTA score was 2 (range, 0-4), and mean (+/- SD) Age-Related White Matter Changes Scale score 6.0 (+/- 4.7). Lacunes were present in 33% of subjects. In unadjusted models, increasing MTA and WMHs were associated with poorer performance on all cognitive tests, and lacunes with poorer performance on the Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, and the Digit Symbol Substitution Test. In multivariable models, including magnetic resonance imaging measures simultaneously, MTA remained a predictor of cognition, whereas WMH had no independent predictive value. There was an interaction between MTA and lacunes: the strength of the association with the Digit Symbol Substitution Test increased with decreasing MTA. CONCLUSIONS: Medial temporal lobe atrophy seems to be a more important predictor of cognition than small-vessel disease in MCI. Lacunes were associated with performance on the Digit Symbol Substitution Test, especially in subjects with milder MTA. Although WMHs were prevalent and associated with cognition in unadjusted analyses, there was no discernible association between WMHs and the cognitive measures in this study after adjustment for age.","Alzheimer Disease [pathology] [physiopathology];Atrophy [etiology] [pathology] [physiopathology];Brain Infarction [pathology] [physiopathology];Cognition Disorders [etiology] [pathology] [physiopathology];Dementia, Vascular [pathology] [physiopathology];Disease Progression;Double-Blind Method;Hippocampus [blood supply] [pathology] [physiopathology];Magnetic Resonance Imaging [methods] [standards];Memory Disorders [etiology] [pathology] [physiopathology];Nerve Fibers, Myelinated [pathology];Placebos;Predictive Value of Tests;Prognosis;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Pol, L. A.;Korf, E. S.;Flier, W. M.;Brashear, H. R.;Fox, N. C.;Barkhof, F.;Scheltens, P.",2007,,10.1001/archneur.64.7.1023,0,
1897,Baseline predictors of rates of hippocampal atrophy in mild cognitive impairment,"OBJECTIVE: A large cohort of subjects with mild cognitive impairment (MCI) was categorized into tertiles based on hippocampal atrophy rates, as a proxy for Alzheimer-type pathology. We compared baseline clinical, neuropsychological, and MRI measures to characterize these MCI subgroups. METHODS: Serial MRI data of 323 subjects with MCI (49% men; mean +/- SD age: 69 +/- 9 years), followed for 2 years in a clinical trial, were available. Baseline hippocampal and whole brain volumes (WBV) were measured, and hippocampal volume change was assessed. Baseline medial temporal lobe atrophy (MTA), white matter hyperintensities (WMH), and lacunes were rated visually. The cohort was categorized into tertiles based on hippocampal atrophy rates (absent, moderate, and severe). RESULTS: Rates of hippocampal atrophy (%/year) were 0.0 +/- 0.8 in the absent, 1.7 +/- 0.4 in the moderate, and 3.6 +/- 1.0 in the severe (mean +/- SD) tertile. Older age and the APOE epsilon 4 allele were associated with higher hippocampal atrophy rates (p < 0.0001 and p = 0.015). General cognition deteriorated over the MCI groups (p < 0.0001), whereas, after adjustment for age and sex, episodic memory and executive function did not. Baseline hippocampal atrophy was associated with increasing atrophy rates (hippocampal volume: p = 0.025; MTA score: p = 0.008); in contrast, WBV, WMH, and lacunes, adjusted for age and sex, were not significantly associated with hippocampal atrophy rates. CONCLUSIONS: In mild cognitive impairment (MCI), older age, poorer general cognition, hippocampal atrophy, and APOE epsilon 4 predict subsequent accelerated rates of hippocampal atrophy, suggestive of the accumulation of Alzheimer-type pathology, which may become clinically manifest in the future. These markers may improve identification of subjects with MCI at risk for Alzheimer disease.","Age Factors;Alzheimer Disease [drug therapy] [pathology] [physiopathology];Apolipoprotein E4 [genetics];Atrophy [etiology] [pathology] [prevention & control];Biomarkers [analysis];Cholinesterase Inhibitors [pharmacology];Cognition Disorders [drug therapy] [pathology] [physiopathology];Cohort Studies;Disease Progression;Double-Blind Method;Follow-Up Studies;Galantamine [pharmacology];Genetic Predisposition to Disease [genetics];Hippocampus [drug effects] [pathology] [physiopathology];Magnetic Resonance Imaging;Nerve Fibers, Myelinated [pathology];Neuropsychological Tests;Predictive Value of Tests;Prognosis;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Pol, L. A.;Flier, W. M.;Korf, E. S.;Fox, N. C.;Barkhof, F.;Scheltens, P.",2007,,10.1212/01.wnl.0000277458.26846.96,0,
1898,The concept of lacuna cerebri from 1838 to the present time,"The term 'lacunes' was first used by Dechambre (1838) referring to small cavities developed during the process of resorption within cerebral softenings. Some years later, 'lacunes' was applied by Durand-Fardel (1843) to small cavities located in the basal ganglia and hypothetically attributed to old, healed cerebral softenings. Durand-Fardel (1842, 1854) described 'l'etat crible' as many round small holes ('criblues') always containing a patent blood vessel and located in the hemispheric white matter. He believed that 'etat crible' was caused by mechanical compression of cerebral tissue related to the dilatation of the blood cerebral vessels during repetitive cerebral congestion. Chronic dementia or delirium were considered as the clinical counterpart of 'etat crible'. In the second half of the XIXth century, the few reports about lacunes were confusing due to the imprecise use of the terms 'lacunes' and 'etat crible'. Furthermore, some authors described lacunes as sequelae of haemorrhage, others as old softenings or both. In the beginning of the XX th century, the magistral work of P. Marie (1901) established a clear distinction between the 'foyers lacunaires de desintegration' and 'etat crible' de Durand-Fardel or single perivascular dilatation of one of the lenticulo-striate arteries at its entrance into the lenticular nucleus or post-mortem charges (cerebral porose, 'etat de fromage de gruyere'). He described lacunes as small cerebral softenings caused by occlusion of the blood vessels by a 'local arteriosclerotic process'. However, he also stated that some lacunes containing a patent blood vessel were due to a perivascular space dilatation destroying the adjacent brain parenchyma by a process of 'destructive vaginalitis'. Marie observed that lacunes were frequently clinically asymptomatic, but 'that the hemiplegia of the old people was more often due to cerebral lacunes than to cerebral haemorrhage or softening'. During the first half of the XX th century, all the papers devoted to cerebral lacunae were in accordance with the work of P. Marie, developping his own's contradictions. Many authors emphazised the 'destructive vaginalitis way' and claimed that lacunes were dilatations of the perivascular spaces. Many other authors developed the 'softening way' magistrally illustrated by Fisher who considered lacunes as small deep infarcts caused by a specific pathological process of lipohyalinosis due to arteriolar wall modification by hypertensive disease. Until Fisher, lacunes were considered as a lesion related to old age, mostly asymptomatic or responsible to more or less diffuse neurological manifestations: hemiplegia, paraplegia, pseudobulbar palsy and/or chronic dementia. Fisher coined the concept of lacunar stroke with special clinical and therapeutic implications. Specific clinical syndromes were described: pure motor stroke, pure sensory stroke, etc. so that in a recent review more than 20 lacunar syndromes were listed. No use of angiography or anticogulant therapy was recommended. The physiopathological and clinical conception of Fisher were rapidly and widely accepted by the international neurological community. However, in recent years, the introduction of CT scan examination as well as the report of new clinicopathological cases challenged the specificity of the clinical syndromes as well as that of the pathophysiology of the lacunar strokes. In conclusion, it must be stressed that the term lacunes is productive of semantic confusion. Therefore, we recommend as a practical tool, to classify lacunes in 3 types: type I (infarcts), type II (haemorrhages) and type III (dilatations of perivascular spaces).",autopsy;brain atrophy;central nervous system;clinical article;histology;human;peripheral vascular system;priority journal;cerebrovascular accident,"Poirier, J.;Derouesne, C.",1985,,,0,
1899,White matter lesions are related to impaired instrumental activities of daily living poststroke,"BACKGROUND: White matter lesions (WMLs) are frequent in elderly people, and have been associated with impaired activities of daily living (ADL) and cognitive decline. We sought to examine the role of WMLs and their extent, in regard to basic ADL, instrumental ADL (IADL), and cognitive functions, in a large well-defined cohort examined 3 months after an ischemic stroke. METHODS: The study group included 395 of 486 consecutive patients aged 55 to 85 years who, 3 months after an ischemic stroke, completed a neuropsychological test battery and magnetic resonance imaging, and structured medical, neurological, and laboratory evaluations; assessment included an interview with a knowledgeable informant. RESULTS: The patients with the most severe WMLs (n = 213) were older, in comparison with those with moderate (n = 71) or mild/no (n = 111) WMLs. These patients also more often had Diagnostic and Statistical Manual of Mental Disorders, Third Edition dementia; had a lower Mini Mental Status score; were more often women; more often had impaired immediate and delayed memory performance, executive dysfunction, and impaired basic ADL and IADL functions; and had more infarcts and cortical or central atrophy in magnetic resonance imaging. However, there were no significant differences among the 3 groups in stroke severity measured on the Scandinavian Stroke Scale, in stroke-related depression as measured by the Beck Depression Inventory, or in stroke type. According to multiple logistic regression analysis, higher age (odds ratio 1.067, 95% confidence interval 1.036-1.01) and impaired IADL (odds ratio 0.852, 95% confidence interval 0.778-0.931) significantly correlated with severe WMLs. CONCLUSIONS: Although the degree of WMLs was not associated with stroke severity, it was associated with global cognitive function, impaired memory functions, executive dysfunction, sex, and impaired basic ADL. Age and IADL functions were independent correlates of severe WMLs.","Activities of Daily Living;Aged;Aged, 80 and over;Brain/ pathology;Brain Ischemia/ complications/pathology/physiopathology;Cognition;Cohort Studies;Female;Finland;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Odds Ratio;Risk Assessment;Risk Factors;Severity of Illness Index;Stroke/etiology/ pathology/physiopathology/psychology;Time Factors","Pohjasvaara, T. I.;Jokinen, H.;Ylikoski, R.;Kalska, H.;Mantyla, R.;Kaste, M.;Erkinjuntti, T.",2007,Nov-Dec,10.1016/j.jstrokecerebrovasdis.2007.08.001,0,
1900,Clinical Features of MRI-Defined Subcortical Vascular Disease,"Background and Purpose: Vascular cognitive impairment and vascular dementia are now seen to extend much beyond the traditional multi-infarct dementia. A more homogeneous subtype is the subcortical ischemic vascular disease (SIVD). We applied magnetic resonance imaging (MRI) criteria based on research criteria for SIVD in a large cohort of patients with ischemic stroke. We compared clinical features of patients with SIVD and patients with other stroke type. Subject and Methods: The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery and MRI, including structured medical, neurologic, and laboratory evaluations; clinical mental status examination; interview of a knowledgeable informant; detailed history of risk factors; and evaluation of stroke type, localization, and syndrome. Results: Patients with SIVD (n = 86) more often had a history of progressive cognitive decline (22.8% vs. 6.9%, P = 0.0002), walking disorder before stroke (27.9% vs. 2.0%, P = 0.02), and urinary difficulties (12.8% vs. 5.6%, P = 0.028) in comparison with patients with other stroke type (n = 251). Of the study population, 107 (31.8%) had DSM-III dementia. The patients with SIVD more often had DSM-III dementia (40.7% vs. 28.7%, P = 0.04), had less severe stroke as measured by Scandinavian Stroke Scale (56.6 vs. 55.1, P = 0.03), were more dependent in activities of daily living (ADL) functions as measured by FAQ scale (8.9 vs. 5.4, P = 0.001), were more dependent in instrumental activities of daily living (IADL) functions as measured by the Lawton scale (5.5 vs 6.3, P = 0.001), and were more depressed as measured by the Beck Depression Inventory (11. 8 vs. 8.4, P = 0.0003) poststroke than the patients without SIVD. The main cognitive domain that differentiated the patients with SIVD from those without was executive dysfunction (51.2% vs. 38.7%, P = 0.04). According to multiple regression model, apracticLatactic gait disorder (odds ratio 2.82, 95% confidence interval 1.21-6.53), ADL functions (odds ratio 1.04, 95% confidence interval 1.01-1.08), and the Beck Depression Inventory (odds ratio 1.05, 95% confidence interval 1.02-1.09) related to SIVD. Conclusions: The most significant clinical features of MRI-defined SIVD were found to be apractic-atactic gait, impaired ADL functions, and depression.",,"Pohjasvaara, T.;Mäntylä, R.;Ylikoski, R.;Kaste, M.;Erkinjuntti, T.",2003,October/December,,0,
1901,"Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia","Background and Purpose - The criteria for vascular dementia (VaD) include definition of the cognitive syndrome and the vascular cause. Different criteria for dementia identify different frequencies and clusters of patients. In addition, variation in defining the cause and etiology may have an effect. We compared different clinical criteria for VaD in series of patients with poststroke dementia. Methods - The study group comprised 107 patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) definition for dementia from a cohort of consecutive patients with ischemic stroke who completed a comprehensive neuropsychological test battery and MRI. The mean age (SD) of the patients was 71.4 (7.6) years. The definitions of vascular cause of VaD were those of the DSM-III (1980), Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC; 1992), International Statistical Classification of Diseases, 10th Revision (ICD-10; 1992), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN; 1993), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; 1994). Results - The number of cases that could be classified as VaD according to the different criteria varied considerably: 36.4% (n=39) by DSM-III, 86.9% (n=93) by ADDTC, 32.7% (n=35) by NINDS-AIREN, 36.4% (n=39) by ICD-10, and 91.6% (n=98) by DSM-IV criteria. The concordance between DSM-III/ICD-10 was perfect (100%; κ=1.0), between ICD-10/NINDS-AIREN and ADDTC/DSM-IV good to moderate (85.0% and 87.3%; κ=0.87 and 0.37, respectively), but otherwise poor between the other criteria. Only 31 patients fulfilled all the criteria for VaD applied. Major discriminating factors between the criteria were requirement of (1) focal neurological signs, (2) unequal distribution of deficits in higher cortical functions, and (3) evidence of relevant CVD based on brain imaging findings. Conclusions - Current criteria of VaD identify different frequencies and clusters of patients and are not interchangeable. Optimally, prospective studies with clinicopathological correlation could identify new criteria. Meanwhile, focus on more homogeneous subtypes (eg, small-vessel subcortical VaD) and detailed neuroimaging criteria could improve the diagnostics.",,"Pohjasvaara, T.;Mäntylä, R.;Ylikoski, R.;Kaste, M.;Erkinjuntti, T.",2000,2000,,0,
1902,"How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia","BACKGROUND: Cerebrovascular disease is a major factor related to cognitive impairment. However, behavioral correlates of ischemic brain lesions are insufficiently characterized. OBJECTIVE: To examine magnetic resonance imaging correlates of dementia in a large, well-defined series of patients with ischemic stroke. METHODS: Detailed medical, neurological, and neuropsychological examinations were conducted 3 months after ischemic stroke for 337 of 486 consecutive patients aged 55 to 85 years. Infarcts (type, site, side, number, and volume), extent of white matter lesions (WMLs), and degree of atrophy were categorized according to magnetic resonance images of the head. The definition for dementia of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) was used. RESULTS: Dementia was diagnosed in 107 (31.8%) of the patients and stroke-related dementia in 87 (25.8%). Volumes, numbers, distinct sites of infarcts, extent of WMLs, and degree of atrophy were different for the demented and nondemented subjects. Particularly, volumes of infarcts in any (right- or left-sided) superior middle cerebral artery territory (27.3 vs 13.7 cm(3), P =. 002) and left thalamocortical connection (14.8 vs 4.0 cm(3), P =. 002) differentiated the 2 groups. Logistic regression analysis showed that the correlates of any dementia included the combination of infarct features (volume of infarcts in any superior middle cerebral artery: odds ratio [OR], 1.11; frequency of left-sided infarcts: OR, 1.21), extent of WMLs (OR, 1.3), medial temporal lobe atrophy (OR, 2.1), and host factors (education; OR, 0.91). In the patients with stroke-related dementia, the main correlate was volume of infarcts in the left anterior corona radiata (OR, 1.68). CONCLUSION: Correlates of poststroke dementia do not include merely 1 feature but a combination of infarct features, extent of WMLs, medial temporal lobe atrophy, and host features.","Aged;Aged, 80 and over;Atrophy/pathology;Brain/blood supply/*pathology;Brain Ischemia/*complications;Cerebral Arteries/pathology;Cognition Disorders/diagnosis/etiology;Dementia/*diagnosis/*etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Severity of Illness Index;Temporal Lobe/blood supply/pathology;Time Factors","Pohjasvaara, T.;Mantyla, R.;Salonen, O.;Aronen, H. J.;Ylikoski, R.;Hietanen, M.;Kaste, M.;Erkinjuntti, T.",2000,Sep,,0,
1903,MRI correlates of dementia after first clinical ischemic stroke,"BACKGROUND AND PURPOSE: Dementia after first clinical stroke frequently has been found, but the clinical and radiological correlates have not been fully detailed. We examined magnetic resonance imaging (MRI) correlates of dementia in a large well-defined series of patients with first clinical ischemic stroke. METHODS: Detailed medical, neurological and neuropsychological examination was conducted 3 months after ischemic stroke for 273 patients with first clinical stroke from a consecutive series of 486 patients aged 55-85 years. MRI of the head categorised infarcts (type, site, side, number, volume), extent of white matter lesions (WMLs) and degree of atrophy. The DSM-III definition for dementia was used. RESULTS: Dementia was diagnosed in 79 (28.9%) of the patients with first clinical stroke. Volumes, numbers, distinct sites of infarcts, extent of WMLs and degree of atrophy were different for the demented and nondemented subjects. Logistic regression analysis showed that the correlates of dementia included the combination of infarct features (volume of infarcts in left-sided anterior corona radiata; OR 1.86), extent of WMLs (OR 1. 37), medial temporal lobe atrophy (OR 3.4) and host factors (low education; OR 1.11). The additive effect of having more than one correlate was detected (OR 2.53). CONCLUSIONS: Dementia occurring after first clinical stroke is frequent and not solely due to a single stroke, but contain a combination of infarcts features, extent of WMLs, medial temporal lobe atrophy and host factors reflecting more than one underlying pathology.",Aged;Brain/blood supply/ pathology/physiopathology;Brain Infarction/complications/epidemiology/pathology;Brain Ischemia/ complications/epidemiology/ pathology;Dementia/epidemiology/ etiology/ pathology;Demography;Female;Humans;Magnetic Resonance Imaging/statistics & numerical data;Male;Prevalence;Stroke/ complications/epidemiology/ pathology,"Pohjasvaara, T.;Mantyla, R.;Salonen, O.;Aronen, H. J.;Ylikoski, R.;Hietanen, M.;Kaste, M.;Erkinjuntti, T.",2000,Dec 1,,0,
1904,Clinical and radiological determinants of prestroke cognitive decline in a stroke cohort,"Objectives - Stroke seems to be related to dementia more often than previously assumed and vascular factors are also related to Alzheimer's disease. The pathophysiology of poststroke dementia includes ischaemic changes in the brain, a combination of degenerative and vascular changes, and changes only related to Alzheimer's disease. Some cognitive decline recognised after a stroke may be due to pre-existing cognitive decline. The aim of this study was to determine the clinical and radiological determinants of prestroke cognitive decline. Methods - The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischaemic stroke completed a comprehensive neuropsychological test battery; structured medical, neurological, and mental status examination; interview of a knowledgeable informant containing structured questions on abnormality in the cognitive functions; assessment of social functions before the index stroke; and MRI. Results - Frequency of prestroke cognitive decline including that of dementia was 9.2% (31/337). The patients with prestroke cognitive decline were older, more often had less than 6 years of education, and had history of previous stroke. Vascular risk factors did not differ significantly between these two groups. White matter changes (p = 0.004), cortical entorhinal, hippocampal, and medial (p < 0.001), cortical (p = 0.008); and any (p < 0.01), but not the frequencies or volumes of old, silent, or all infarcts on MRI differentiated those with and without prestroke cognitive decline. The correlates of prestroke cognitive decline in logistic regression analysis were medial temporal cortical atrophy (odds ratio (OR) 7.5, 95% confidence interval (95%CI) 3.2-18.2), history of previous ischaemic stroke (OR 4.4, 95% CI 1.8-10.6),and education (OR 0.9, 95% CI 0.8-0.9). Conclusions - History of previous stroke, but not volumes or frequencies was found to correlate with prestroke cognitive decline. Other associating factors were rather those usually associated with degenerative dementia: white matter changes and cerebral atrophy; and in multiple models medial temporal cortical atrophy and education. The possible overlap between two or more underlying diseases must be remembered in diagnosis and treatment of patients with vascular cognitive impairment.",adult;age;aged;article;brain atrophy;brain infarction;clinical feature;cognitive defect;dementia;differential diagnosis;disease association;education;entorhinal cortex;frontal cortex;hippocampus;human;interview;major clinical study;medical examination;mental health;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;pathophysiology;priority journal;radiodiagnosis;regression analysis;risk factor;social status;cerebrovascular accident;temporal cortex;white matter,"Pohjasvaara, T.;Mäntylä, R.;Aronen, H. J.;Leskelä, M.;Salonen, O.;Kaste, M.;Erkinjuntti, T.",1999,,,0,
1905,"Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers-The VMCI-Tuscany Study: Rationale, Design, and Methodology","Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD.",,"Poggesi, A.;Salvadori, E.;Pantoni, L.;Pracucci, G.;Cesari, F.;Chiti, A.;Ciolli, L.;Cosottini, M.;Del Bene, A.;De Stefano, N.;Diciotti, S.;Dotti, M. T.;Ginestroni, A.;Giusti, B.;Gori, A. M.;Nannucci, S.;Orlandi, G.;Pescini, F.;Valenti, R.;Abbate, R.;Federico, A.;Mascalchi, M.;Murri, L.;Inzitari, D.",2012,,10.1155/2012/608013,0,
1906,Neurological abnormalities predict disability: The LADIS (Leukoaraiosis and DISability) study,"To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline. © 2014 Springer-Verlag Berlin Heidelberg.",,"Poggesi, A.;Gouw, A.;Van Der Flier, W.;Pracucci, G.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Ferro, J. M.;Blahak, C.;Langhorne, P.;O'Brien, J.;Schmidt, R.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Scheltens, P.;Inzitari, D.;Pantoni, L.",2014,June,,0,
1907,Cerebral microbleeds are associated with worse cognitive function: The Rotterdam Scan Study,"Objective: Cerebral microbleeds are frequently found in the general elderly population and may reflect underlying vascular disease, but their role in cognitive function is unknown. Methods: We investigated the association between cerebral microbleeds and performance in multiple cognitive domains in 3,979 persons without dementia (mean age, 60.3 years). Mini-Mental State Examination (MMSE) score and neuropsychological tests were used to assess global cognition and the following cognitive domains: memory, information processing speed, executive function, and motor speed. We used number of microbleeds as continuous variable, and additionally distinguished between persons with no microbleeds, 1 microbleed, 2-4 microbleeds, and ≥5 microbleeds. The association of microbleeds with different cognitive domains was estimated using linear regression models. Additional adjustments were made for vascular risk factors, brain atrophy, and other imaging markers of cerebral small vessel disease. We stratified analyses by location of microbleeds. Results: A higher number of microbleeds was associated with lower MMSE score and worse performance on tests of information processing speed and motor speed. When analyzed per category, presence of 5 or more microbleeds was associated with worse performance in all cognitive domains, except memory. These associations were most robust in participants with strictly lobar microbleeds, whereas after additional adjustments associations disappeared for deep or infratentorial microbleeds. Conclusions: Presence of numerous microbleeds, especially in a strictly lobar location, is associated with worse performance on tests measuring cognitive function, even after adjustments for vascular risk factors and other imaging markers of small vessel disease. These results suggest an independent role for microbleed-associated vasculopathy in cognitive impairment. Copyright © 2012 by AAN Enterprises, Inc.",,"Poels, M. M. F.;Ikram, M. A.;Van Der Lugt, A.;Hofman, A.;Niessen, W. J.;Krestin, G. P.;Breteler, M. M. B.;Vernooij, M. W.",2012,31,,0,
1908,Initial experience with technetium-99m HM-PAO brain SPECT,"Technetium-99m hexamethylpropyleneamineoxime ([99mTc]HM-PAO) brain single photon emission computed tomography (SPECT) was performed with a dual head rotating scintillation camera. Normal tracer distribution and side/side differences of counting rates were obtained in 11 healthy volunteers. Almost stable gray/white matter ratios were found (1.97-2.1) in one normal subject during 2 hr after tracer administration. Eighty-three investigated patients had the following diagnoses (in parentheses is percent of positive findings in each group): cerebral vascular disease 18 (94.4%), epilepsy 23 (82.6%), extrapyramidal disorders 8 (100%), dementia 12 (100%), headache 11 (63.6%), psychiatric disorders 11 (27.3%). In addition, SPECT was performed in 28 male volunteers during motor or visual imagery tasks and a significant increase (p = 0.035) of relative tracer deposition was observed in the left inferior occipital region during visual imagery when compared with motor imagery. The results indicate that [99mTc]HM-PAO SPECT is valuable for demonstrating pathologic and physiologic changes of the brain.","Adult;Aged;Basal Ganglia Diseases/radionuclide imaging;Brain/ radionuclide imaging;Cerebrovascular Circulation;Cerebrovascular Disorders/radionuclide imaging;Dementia/physiopathology;Epilepsy/radionuclide imaging;Female;Headache/radionuclide imaging;Humans;Imagination/physiology;Male;Mental Disorders/physiopathology;Middle Aged;Organometallic Compounds;Oximes;Technetium;Technetium Tc 99m Exametazime;Tomography, Emission-Computed","Podreka, I.;Suess, E.;Goldenberg, G.;Steiner, M.;Brucke, T.;Muller, C.;Lang, W.;Neirinckx, R. D.;Deecke, L.",1987,Nov,,0,
1909,Physical activity and white matter lesion progression: assessment using MRI,"We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.",*Activities of Daily Living;Aged;Alzheimer Disease/*epidemiology/*pathology;Cognition Disorders/*epidemiology/pathology;Cohort Studies;Demyelinating Diseases/*epidemiology/*pathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging/statistics & numerical data;Male;*Motor Activity;United States/epidemiology,"Podewils, L. J.;Guallar, E.;Beauchamp, N.;Lyketsos, C. G.;Kuller, L. H.;Scheltens, P.",2007,Apr 10,10.1212/01.wnl.0000259063.50219.3e,0,
1910,Tc-99m HMPAO brain SPECT imaging in chronic Lyme disease,"Patients with Lyme disease may experience neuropsychiattic problems that persist even after standard courses of antibiotic therapy. Objective detection of neuroimaging brain abnormalities can be helpful to the clinician by demonstrating either focal or diffuse deficits, thereby supporting a CNS origin to the neuropsychiatric problems. To examine the potential utility of SPECT brain imaging in the evaluation of chronic Lyme disease (CLD), two questions were addressed: 1) Are SPECT brain scans abnormal in CLD patients with neuropsychiatric findings? and 2) If abnormal, are the perfusion abnormalities specific for CLD? SPECT brain scans of 19 patients with CLD and 14 non-CLD patients with other neurological diagnoses resulting in perfusion abnormalities were evaluated in a blinded read without reference to clinical status. Scans were randomly ordered for interpretation by three experienced SPECT readers. Final interpretation was arrived at by consensus. Scans were interpreted as normal, abnormal-focal hypoperfusion, or abnormal-diffuse hypoperfusion. Hypoperfusion was described as homogenous or heterogenous. Results were analyzed as percent normal or abnormal and pattern of abnormality. CLD SPECT scans were interpreted as abnormal in 14 of 19 (74%) scans, each characterized as heterogeneous with or without globally decreased perfusion. One CNSLD scan showed a focal lesion. CLD patterns could be distinguished from non-LD patients with a diagnosis of Alzheimer's or Moya-Moya disease but not from non-LD patients with a diagnosis of Creutzfeldt-Jacob disease, Lupus, cerebral vasculitis, or chronic fatigue syndrome. Of the 14 patients who had brain MRI scans, only 2 (14.3%) were abnormal, revealing white matter hyperintensities. These findings suggest that brain SPECT may be a more sensitive tool than MRI for identifying brain abnormalities in CLD, but that the heterogenenous pattern is not specific to CLD.",,"Plutchok, J. J.;Tikofsky, R. S.;Liegner, K. B.;Kochevar, J. M.;Fallon, B. A.;Van Heertum, R. L.",1999,1999,,0,
1911,Diffusion-weighted and diffusion tensor magnetic resonance brain imaging: Principles and applications,"Diffusion Weighted Imaging (DWI) is one of the most recent products of Magnetic Resonance (MR) technology evolution. DWI has been proposed as a noninvasive tool for evaluating structural and physiologic states in biologic tissues as hyperacute ischemic changes within brain tissue. Recently, its more complex and detailed evolution, Diffusion Tensor Imaging (DTI), has been introduced and its clinical applications are the evaluation of anatomical structures and pathologic processes in white matter. White matter quantitative maps that indicate the integrity of brain tissue, color map, and tractography that identifies macroscopic three-dimensional architecture of fiber tracts (e.g., projections and association pathways) can be obtained with DTI. Diffusion weighted imaging visualization techniques (ADC and Trace) are applied for the study of stroke, in the differential diagnosis of expansive lesions (e.g. epidermoid vs. arachnoid cyst) and in detecting traumatic and other lesions associated with restricted diffusion (e.g. MS plaques). On the other hand, DTI provides the identification of abnormalities in the otherwise normal appearing white matter with the understanding of the organization of the fibers, both in tumors and in other cortical or white matter diseases (including stroke, dementias, demyelinating-dismyelinating diseases, epilepsy, schizophrenia). Furthermore, in combination with functional MR, DTI might contribute to the comprehension of brain development, aging and connectivity, thus having a significant impact on brain functional studies.",,"Pizzini, F.;Beltramello, A.;Piovan, E.;Alessandrini, F.",2003,Apr,,0,
1912,"Leukoencephalopathy with swelling, megalencephalopathy and surprisingly mild course. A case report","Leukoencephalopathy with swelling and a discrepantly mild clinical course is a recently identified syndrome described by van der Knaap et al. It is characterised by macrocephaly occurring during the first year of life, initially normal or nearly normal development, slowly progressive ataxia and spasticity with initial preservation of intellectual functions. MRI shows diffuse abnormality of signal intensity in the hemisphere white matter with subcortical cyst-like spaces in the fronto-parietal and anterior temporal areas. The case of a 5-year-old boy whose clinical and neuroimaging findings are consistent with this syndrome is reported. The clinical and neuroimaging findings of this case may provide further information about this new syndrome which could possibly be useful also for genetic counselling.",article;brain;brain edema;case report;congenital malformation;hospitalization;human;male;multiinfarct dementia;newborn;nuclear magnetic resonance imaging,"Pisaturo, C.;Biancheri, R.;Perrone, M. V.;Rossi, A.;Veneselli, E.",1999,,,0,
1913,Rapidly progressive dementia due to leukocytoclastic vasculitis of the central nervous system,"A 70-year-old male was admitted with a 2-week progressive course of severe cognitive impairment, scoring three on the Mini Mental State Examination. MRI of the brain showed confluent hyperintense areas in T2/FLAIR in the periventricular and subcortical white matter, extending to right parietal cortex and basal ganglia. Intra-arterial angiography was unremarkable. A targeted stereotactic brain biopsy disclosed a leukocytoclastic vasculitis. The patient improved on steroids. Leukocytoclastic vasculitis adds to the spectrum of histopathologic subtypes of primary angiitis of the central nervous system. Copyright 2011 BMJ Publishing Group. All rights reserved.",prednisolone;aged;article;basal ganglion;brain angiography;brain biopsy;case report;cerebrospinal fluid analysis;cognitive defect;dementia;depression;differential diagnosis;erythrocyte sedimentation rate;gliosis;human;human tissue;hypothalamus periventricular nucleus;inflammatory cell;inflammatory infiltrate;leukocytoclastic vasculitis;male;Mini Mental State Examination;nuclear magnetic resonance imaging;parietal cortex;priority journal;protein cerebrospinal fluid level;rapidly progressive dementia;stereotactic biopsy;subcortex;white matter,"Pires, C.;Foreid, H.;Barroso, C.;Ferro, J. M.",2011,,,0,
1914,Xenon CT in Alzheimer's disease,"Diagnosis of Alzheimer's disease is based on clinical assessment. Nonetheless, neuroradiological investigation is important to rule out other possible causes of dementia and to quantify possible indicators of the disease stage for the purposes of correlation with clinical severity. MR imaging and functional nuclear medicine techniques (SPET, PET) are useful and can be flanked by xenon CT which has disclosed a significant decrease in cerebral blood flow in the frontotemporal region in Alzheimer patients compared with controls. Reduced cerebral flow was mainly found in the cortical region in mild patients, whereas the reduction also extended more severely to the basal nuclei and hemispheric white matter in moderate cases.",,"Piovan, E.;Puppini, G.;Alessandrini, F.;Pizzini, F.;Zampieri, P.;Foroni, R.;Gambina, G.;Beltramello, A.",1999,1999,,0,
1915,Do eye movement impairments in patients with small vessel cerebrovascular disease depend on lesion load or on cognitive deficits? A video-oculographic and MRI study,"Small vessel cerebrovascular disease (SVCD) is one of the most frequent vessel disorders in the aged brain. Among the spectrum of neurological disturbances related to SVCD, oculomotor dysfunction is a not well understood symptom- in particular, it remains unclear whether vascular lesion load in specific brain regions affects oculomotor function independent of cognitive decline in SVCD patients or whether the effect of higher brain function deficits prevails. In this study, we examined a cohort of 25 SVCD patients and 19 healthy controls using video-oculographic eye movement recording in a laboratory environment, computer-based MRI assessment of white matter lesion load (WMLL), assessment of extrapyramidal motor deficits, and psychometric testing. In comparison to controls, the mean WMLL of patients was significantly larger than in controls. With respect to eye movement control, patients performed significantly worse than controls in almost all aspects of oculomotion. Likewise, patients showed a significantly worse performance in all but one of the neuropsychological tests. Oculomotor deficits in SVCD correlated with the patients' cognitive dysfunctioning while there was only weak evidence for a direct effect of WMLL on eye movement control. In conclusion, oculomotor impairment in SVCD seems to be mainly contingent upon cognitive deterioration in SVCD while WMLL might have only a minor specific effect upon oculomotor pathways. © 2014 Springer-Verlag Berlin Heidelberg.",adult;aged;article;brain region;cerebrovascular disease;clinical article;cognitive defect;computer;controlled study;eye movement control;female;human;male;mental deterioration;middle aged;neuropsychological test;nuclear magnetic resonance imaging;oculography;oculomotor system;priority journal;small vessel cerebrovascular disease;very elderly;videorecording;white matter lesion,"Pinkhardt, E. H.;Issa, H.;Gorges, M.;Jürgens, R.;Lulé, D.;Heimrath, J.;Müller, H. P.;Ludolph, A. C.;Becker, W.;Kassubek, J.",2014,,,0,
1916,Brain atrophy in Alzheimer's Disease and aging,"Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression.",,"Pini, L.;Pievani, M.;Bocchetta, M.;Altomare, D.;Bosco, P.;Cavedo, E.;Galluzzi, S.;Marizzoni, M.;Frisoni, G. B.",2016,,,0,
1917,White matter damage disorganizes brain functional networks in amnestic mild cognitive impairment,"Although progressive functional brain network disruption has been one of the hallmarks of Alzheimer's Disease, little is known about the origin of this functional impairment that underlies cognitive symptoms. We investigated how the loss of white matter (WM) integrity disrupts the organization of the functional networks at different frequency bands. The analyses were performed in a sample of healthy elders and mild cognitive impairment (MCI) subjects. Spontaneous brain magnetic activity (measured with magnetoencephalography) was characterized with phase synchronization analysis, and graph theory was applied to the functional networks. We identified WM areas (using diffusion weighted magnetic resonance imaging) that showed a statistical dependence between the fractional anisotropy and the graph metrics. These regions are part of an episodic memory network and were also related to cognitive functions. Our data support the hypothesis that disruption of the anatomical networks influences the organization at the functional level resulting in the prodromal dementia syndrome of MCI.","Aged;Aged, 80 and over;Amnesia/ physiopathology;Brain/pathology/ physiopathology;Brain Mapping/methods;Case-Control Studies;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Magnetoencephalography/methods;Male;Mild Cognitive Impairment/ physiopathology;Nerve Net/ physiopathology;White Matter/pathology","Pineda-Pardo, J. A.;Garces, P.;Lopez, M. E.;Aurtenetxe, S.;Cuesta, P.;Marcos, A.;Montejo, P.;Yus, M.;Hernandez-Tamames, J. A.;del Pozo, F.;Becker, J. T.;Maestu, F.",2014,Jun,10.1089/brain.2013.0208,0,
1918,Stroke in critically ill patients,"Advances in critical care medicine have led to improved survival rates among patients admitted to the Intensive Care unit (ICU), but complications experienced during admittance in an ICU may influence long-term outcome and the neurocognitive state of these patients. Coagulation disorders, glucose intolerance, diabetes, pro-inflammatory state and underlying severe pathologies are common risk factors for stroke development in ICU patients. Stroke may result in very serious consequences like motor function impairment, neglect and aphasia, but in some cases, stroke may not result in any clinical sign in acute phase. Recently, more attention has been given to this condition called ""silent stroke."" ""Silent stroke"" could be the foundation of the development of neurocognitive impairment and vascular dementia. In ICU survivors, approximately 1/3 of patients or more will develop chronic neurocognitive impairment. With the advent of sensitive techniques for brain imaging, silent brain lesions, including brain infarct and white matter changes, have been frequently recognized. Until now, epidemiological studies in this field evaluating incidence and consequences of stroke in ICU setting are lacking, and prospective studies are required to evaluate the impact of this condition on the quality of life, neurocognitive outcome and mortality of ICU patients. We believe that when stroke occurs in critically ill patients, more attention is typically given to the underlying pathologies than stroke, and this may influence the long-term outcome. Guidelines for the early management of stroke, commonly used in Stroke Units, should be followed, even in critically ill patients in an ICU setting.",,"Pilato, F.;Profice, P.;Dileone, M.;Ranieri, F.;Capone, F.;Minicuci, G.;Tagliente, D.;Florio, L.;Di Iorio, R.;Plantone, D.;Tonali, P. A.;Di Lazzaro, V.",2009,May,,0,
1919,Are MRI white matter lesions clinically significant in the 'old-old'? Evidence from the Sydney Older Persons Study,"BACKGROUND: The number of individuals aged over 80 years is the fastest increasing group in developed countries. White matter lesions (WML) observed on magnetic resonance imaging (MRI) have uncertain clinical significance, particularly in the old. OBJECTIVES: To determine the prevalence of periventricular and deep WML in survivors of an original cohort of randomly selected elderly community dwellers, and to examine their associations with clinical markers of vascular and extrapyramidal disorders of ageing, as well as quantitative cognitive measures. METHODS: Brain MRI, lifestyle interview, cognitive testing and medical examination were administered to 122 participants from the Sydney Older Persons Study 6-year review (mean age: 85.5 years). Apolipoprotein E (ApoE) genotype was also established. Presence and severity of periventricular and deep WML were ascertained using semi-quantitative rating methods and their relations to the cognitive and clinical variables investigated. RESULTS: Periventricular WML were present in all participants in similar severity for all three regions sampled. In contrast, a gradient of severity was observed for the deep WML: most severe in the parietal region, followed by the frontal and occipital regions, and least severe in the temporal region. Associations with gender or with the ApoE epsilon4 allele were non-significant. WML were inconsistently associated with age and cognitive functioning or with the clinical markers of dementia. No frontal specificity emerged. Examination of individual lesion types did not change the general pattern of associations. Supporting evidence for a threshold effect was observed on some measures. CONCLUSIONS: WML are extremely common in elderly, non-demented individuals. Unlike in younger individuals, MRI abnormalities may not be evidence of a current pathological process and their importance may change with advancing age.","Aged;Aged, 80 and over;Brain/ pathology;Cognition Disorders/etiology/ pathology;Female;Geriatric Assessment;Humans;Life Style;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Reproducibility of Results;Risk Factors","Piguet, O.;Ridley, L.;Grayson, D. A.;Bennett, H. P.;Creasey, H.;Lye, T. C.;Broe, G. A.",2003,,68482,0,
1920,Single photon emission computed tomography,"Single photon emission computed tomography (SPECT) is becoming an increasingly important part of routine clinical nuclear medicine. By providing tomographic reconstructions in multiple planes through the patient, SPECT expands the clinical applications in nuclear medicine as well as providing better contrast, edge definition and separation of target from background activities. Imaging techniques have been developed for the evaluation of regional cerebral blood flow using radiolabeled amines. Thus cerebral functional imaging can be used in the diagnosis of acute cerebral infarction, cerebral vascular disease, dementia and epilepsy. SPECT plays a complementary role in the evaluation of coronary artery disease, particularly when it is coupled with thallium-201 and exercise testing. SPECT extends our diagnostic capabilities in additional areas, such as liver and bone scintigraphy as well as tumor imaging with gallium-67.","Brain/radionuclide imaging;Cerebral Infarction/radionuclide imaging;Diphosphates;Heart/radionuclide imaging;Image Enhancement;Liver/radionuclide imaging;Myocardial Infarction/radionuclide imaging;Radioisotopes;Technetium;Technetium Tc 99m Pyrophosphate;Thallium;Tomography, Emission-Computed/methods","Piez, C. W., Jr.;Holman, B. L.",1985,Jul-Aug,,0,
1921,Pattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers,"Background To investigate the patterns of brain atrophy, white matter (WM) tract changes, and functional connectivity (FC) abnormalities in asymptomatic granulin (GRN) mutation carriers.Methods Ten cognitively normal subjects (five mutation carriers, GRN+; years to estimated disease onset: 12 ± 7; five mutation noncarriers, GRN-) underwent a clinical and imaging (structural, diffusion tensor, and resting-state functional magnetic resonance imaging) assessment. Brain atrophy was measured with cortical thickness analysis, WM abnormalities with tract-based spatial statistics, and FC with independent component analysis.Results GRN+ showed smaller cortical thickness than GRN- in the right orbitofrontal and precentral gyrus and left rostral middle frontal gyrus. WM tracts abnormalities were limited to increased axial diffusivity in the right cingulum, superior longitudinal fasciculus, and corticospinal tract. There were no differences in FC of resting-state networks.Conclusion Brain atrophy and WM tract abnormalities in frontal-parietal circuits can be detected at least a decade before the estimated symptom onset in asymptomatic mutation carriers.",,"Pievani, M.;Paternicò, D.;Benussi, L.;Binetti, G.;Orlandini, A.;Cobelli, M.;Magnaldi, S.;Ghidoni, R.;Frisoni, G. B.",2014,1,,0,
1922,Structural and diffusion tensor imaging in mci subjects with intermediate riskofalzheimer's disease based on csf profile,"Background: Subjects with mild cognitive impairment (MCI) and abnormal levels of CSF Abeta42, Abeta42/t-tau and/or Abeta42/p-tau ratios (MCI-pos) are at high risk of cognitive decline, while those with negative CSF levels (MCI-neg) are generally stable or at low-risk. MCI with intermediate CSF levels (i.e. not clearly positive nor clearly negative, MCI-int) fall into a ""grey zone"" where prediction of conversion is more challenging. Aim of this study was to investigate if MCI-int show any evidence of Alzheimer's disease (AD) signatures as assessed on structural and diffusion tensor (DT) MRI. Methods:147 MCI subjects were enrolled across 13 centres in Europe. All subjects underwent clinical, 3T MRI (structural and DT) and CSF collection. Medial temporal lobe atrophy (hippocampal volume and medial temporal cortex thickness) were computed with Freesurfer. Fractional anisotropy (FA) in the major white matter tracts (genu and splenium of the corpus callosum, cingulum, parahippocampal tract, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract) was computed with atlas-based ROI analysis. Analysis of covariance (age- and gender-corrected) was used to extract AD signatures in MCI-pos and imaging abnormalities in MCI-int versus MCI-neg were assessed with Bonferroni post-hoc. Results: There were no differences in cognition (memory, attention, executive functions) in MCI-int for all the classifications. In structural and DT MRI areas affected in MCI-pos (right medial temporal thickness, splenium of corpus callosum, bilateral parahippocampal tract), Abeta42 classification detected no difference in MCI-int vs MCI-neg. Conversely, for the Abeta42/p-tau classification MCI-int showed significant atrophy in the right hippocampus. DT MRI reported reduced FA in the right parahippocampal tract of MCI-int for both Abeta42/t-tau and Abeta42/p-tau classifications. Conclusions: Patients classified as MCI-int by the two ratios had structural features more similar to MCI-pos than MCI-neg. Indeed, they reported significant differences in areas already affected in MCI-pos and might therefore indicate early AD. Conversely, Abeta42 classification did not detect any significant difference in MCI-int, possibly being less sensitive to early AD changes either indicating a pathologically heterogeneous group.",Alzheimer disease;analysis of covariance;atrophy;attention;cingulum (brain);classification;clinical trial;congenital malformation;controlled clinical trial;controlled study;corpus callosum;diffusion tensor imaging;Europe;executive function;extract;female;fractional anisotropy;gender;human;imaging software;inferior longitudinal fasciculus;major clinical study;male;medial temporal lobe;memory;mild cognitive impairment;multicenter study;pyramidal tract;right hippocampus;superior longitudinal fasciculus;temporal cortex;thickness;amyloid beta-protein (1-42),"Pievani, M.;Marizzoni, M.;Pini, L.;Jovicich, J.;Nobili, F.;Ranjeva, J. P.;Bartres-Faz, D.;Fiedler, U.;Schonknech, P.;Payoux, P.;Beltramello, A.;Caulo, M.;Soricelli, A.;Parnetti, L.;Tsolaki, M.;Rossini, P. M.;Visser, P. J.;Albani, D.;Forloni, G.;Bordet, R.;Richardson, J.;Blin, O.;Frisoni, G. B.",2017,,,0,
1923,Assessment of white matter tract damage in mild cognitive impairment and Alzheimer's disease,"Diffusion tensor MRI-based tractography was used to investigate white matter (WM) changes in the major limbic (i.e., fornix and cingulum) and cortico-cortical association pathways [i.e., the uncinate fasciculus, the inferior fronto-occipital fasciculus, the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus, and the corpus callosum] in 25 Alzheimer's disease (AD) patients, 19 amnestic mild cognitive impairment (aMCI) patients, and 15 healthy controls (HC). Mean diffusivity (MD), fractional anisotropy (FA), as well as axial (DA) and radial (DR) diffusivities were measured for each tract, using an atlas-based tractography approach. The association of WM tract integrity with hippocampal volume was also assessed. MD values were significantly different among groups in all WM tracts (P values ranging from 0.002 to 0.03), except in the fornix (P = 0.06) and the inferior fronto-occipital fasciculus (P = 0.09). Conversely, FA was significantly different among groups in the fornix only (P = 0.02). DA values were significantly different among groups in all WM tracts (P values ranging from 0.001 to 0.01), except in the fornix (P = 0.13) and the cingulum (P = 0.29). Significantly different DR values among groups were found in the fornix (P = 0.02) and the ILF (P = 0.01). In the fornix and cingulum, DR was significantly more increased than DA in both patient groups compared to HC. No difference in DA versus DR was found in cortico-cortical WM tracts. DA values in the fornix were significantly correlated with the hippocampal volume. This study demonstrates a different pattern of WM involvement in the limbic and cortico-cortical association pathways in aMCI and AD patients.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*pathology;Brain/*pathology/physiopathology;Cognition Disorders/diagnosis/*pathology;Disease Progression;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neural Pathways/pathology/physiopathology;Severity of Illness Index","Pievani, M.;Agosta, F.;Pagani, E.;Canu, E.;Sala, S.;Absinta, M.;Geroldi, C.;Ganzola, R.;Frisoni, G. B.;Filippi, M.",2010,Dec,10.1002/hbm.20978,0,
1924,CSF beta-amyloid and white matter damage: a new perspective on Alzheimer's disease,"OBJECTIVE: To assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls. METHODS: Eighty-five participants were recruited: 65 with newly diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. beta-amyloid1-42 (Abeta) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Abeta levels (Abeta(+)), while 23 had normal CSF Abeta levels (Abeta(-)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. RESULTS: We found an increased WM-LL in Abeta(+) compared with both, healthy controls (p=0.003) and Abeta(-) patients (p=0.02). Interestingly, CSF Abeta concentration was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Abeta(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001). CONCLUSIONS: WM damage is crucial in AD pathogenesis. The correlation between CSF Abeta levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.",dementia;multiple sclerosis;myelin;neroimmunology;neuroradiology,"Pietroboni, A. M.;Scarioni, M.;Carandini, T.;Basilico, P.;Cadioli, M.;Giulietti, G.;Arighi, A.;Caprioli, M.;Serra, L.;Sina, C.;Fenoglio, C.;Ghezzi, L.;Fumagalli, G. G.;De Riz, M. A.;Calvi, A.;Triulzi, F.;Bozzali, M.;Scarpini, E.;Galimberti, D.",2017,Oct 20,,0,
1925,Phenotypic heterogeneity of the GRN Asp22fs mutation in a large italian kindred,"The Asp22fs(g.63-64insC) mutation in progranulin gene (GRN) has been so far reported in one patient who developed frontotemporal dementia (FTD) at the age of 65. Here, we describe the clinical heterogeneity associated with the GRN Asp22fs mutation in a large Italian family. Clinical and instrumental workup of two symptomatic carriers in two generations has been carried out, together with genetic analysis of probands and of nine asymptomatic family members. The first proband was a 47-year old male clinically diagnosed with FTD. Family history was positive and suggestive of an autosomal dominant pattern of inheritance. Evaluation of plasma GRN levels was consistent with the presence of a mutation in its encoding gene, that was demonstrated by sequencing [Asp22fs(g.63-64insC)] . Brain MRI showed multiple T2 and FLAIR hyperintense areas in the frontal lobe white matter and right hemisphere cortical atrophy. The second proband was his 79 year old uncle, presenting with mild cognitive impairment. Brain MRI showed small T2 hyperintense lesions and widespread cortical atrophy. Cerebrospinal fluid amyloid-β, tau, and phosphotau protein levels were in both cases in the range of normality. Additional nine asymptomatic family members were studied. This family's description expands the spectrum of clinical presentations of frontotemporal lobar degeneration caused by GRN mutations, suggesting that the diagnosis could be missed in some individuals with an atypical presentation, and points up the importance of GRN plasma level evaluation. © 2011 - IOS Press and the authors. All rights reserved.",amyloid beta protein[1-42];aspartic acid;progranulin;tau protein;adult;aged;amino acid sequence;article;autosomal dominant inheritance;brain atrophy;cerebrospinal fluid analysis;clinical article;clinical evaluation;family history;female;frontal lobe;frontotemporal dementia;gene mutation;gene sequence;genetic analysis;genotype;human;Italy;male;mild cognitive impairment;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;onset age;pedigree analysis;phenotype;priority journal;protein blood level;right hemisphere;white matter,"Pietroboni, A. M.;Fumagalli, G. G.;Ghezzi, L.;Fenoglio, C.;Cortini, F.;Serpente, M.;Cantoni, C.;Rotondo, E.;Corti, P.;Carecchio, M.;Bassi, M.;Bresolin, N.;Galbiati, D.;Galimberti, D.;Scarpini, E.",2011,,,0,
1926,Association between atrial fibrillation and volumetric magnetic resonance imaging brain measures: Framingham Offspring Study,"BACKGROUND: The increased risk of stroke and cognitive impairment associated with atrial fibrillation (AF) is well documented. However, there is a paucity of research investigating the relations between AF and brain morphology. OBJECTIVE: The purpose of this study was to investigate the association between AF and brain volume measures on magnetic resonance imaging (MRI). METHODS: The study sample included stroke- and dementia-free participants who attended the Framingham Heart Study offspring cohort 7th examination cycle (1999-2005) and underwent contemporaneous MRI. We examined the association between prevalent AF and brain volume measures (total cerebral volume, frontal lobe volume, temporal lobe volume, temporal horn volume, hippocampal volume, and white matter hyperintensity volume) with linear regression. We first adjusted models for age and sex, and then for vascular risk factors and APOE4. RESULTS: We studied 2144 individuals (mean age 61.8 +/- 9.3 years; 54% women); 73 participants (3.4%) had prevalent AF at the time of MRI. In age- and sex-adjusted models, AF was inversely associated with total cerebral brain volume, frontal brain volume, and temporal brain volume. After further adjustment for vascular risk factors and APOE4, AF remained associated with frontal brain volume. CONCLUSION: After accounting for vascular risk factor burden, prevalent AF was associated with lobar indexes of vascular brain aging but not with expected white matter changes.",Atrial fibrillation;Brain volume;Framingham;Imaging;Magnetic resonance imaging,"Piers, R. J.;Nishtala, A.;Preis, S. R.;DeCarli, C.;Wolf, P. A.;Benjamin, E. J.;Au, R.",2016,Oct,10.1016/j.hrthm.2016.07.004,0,
1927,Longitudinal study of carotid atherosclerosis and white matter hyperintensities: the EVA-MRI cohort,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are often observed on cerebral magnetic resonance imaging (MRI) of elderly individuals. Epidemiological studies have shown that age and hypertension are associated with WMHs, suggesting a vascular mechanism in WMH pathogenesis. In a population-based prospective study, we examined the association of carotid atherosclerosis measured at baseline and 4-year follow-up with severity of WMHs assessed at 4-year follow-up. METHODS: The sample consisted of 640 healthy subjects aged 59-71 years at entry enrolled in the prospective EVA Study. Systolic and diastolic blood pressures were measured at each wave. Ultrasonographic measures of intima-media thickness (IMT) of the common carotid arteries and plaques were made at baseline and at 4-year follow-up examination. An MRI examination was performed at 4-year follow-up. The presence and severity of WMHs were evaluated by a single radiologist. RESULTS: After adjusting for age, gender, and hypertension, the presence of carotid plaques at baseline was significantly associated with the presence of severe WMHs 4 years later [odds ratio (OR) = 1.70; 95% confidence interval (CI): 1.05-2.74]. The association was stronger in men than in women. A 0.1-mm increase of baseline IMT was associated with an increased risk of severe WMHs in both sexes (adjusted OR = 1.17; 95% CI: 0.96-1.41), but the association was not significant (p = 0.12). Cross-sectional relationships between carotid plaques and severe WMHs at 4-year follow-up showed that the risk of having severe WMHs was stronger in the group of subjects who had already plaques at study entry compared to the group of subjects whose plaques occurred during 4-year follow-up. CONCLUSION: This study confirmed an association between carotid atherosclerosis and WMHs independently of age and hypertension. It also suggested that the older the carotid plaques, the higher the risk of having severe WMHs.","Aged;Brain/ pathology;Carotid Artery Diseases/complications/diagnosis/ epidemiology;Carotid Artery, Common/ultrasonography;Dementia, Vascular/ pathology;Female;Follow-Up Studies;France/epidemiology;Humans;Hypertension/complications/diagnosis/epidemiology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Prevalence;Prospective Studies;Risk Factors;Severity of Illness Index;Tunica Intima/pathology/ultrasonography;Tunica Media/pathology/ultrasonography","Pico, F.;Dufouil, C.;Levy, C.;Besancon, V.;de Kersaint-Gilly, A.;Bonithon-Kopp, C.;Ducimetiere, P.;Tzourio, C.;Alperovitch, A.",2002,,,0,
1928,Routine' brain CT in psychiatric patients - Does it make sense?,"Purpose: To prospectively assess the spectrum of brain CT findings in psychiatric patients and to determine the number of patients that had an underlying cause for the symptoms. Patients and methods: Over a period of six months, 142 patients (78 males, 64 females; median age 61 [18-91] years) were referred for CT brain scans. Their scans were reviewed, along with the clinical information that was provided in the request form. All the hard copies were reviewed to assess areas of ischaemia, infarction, atrophy, tumours, and haematomas. The majority of requests were to exclude vascular event or space-occupying lesions. Clinical indications included mood disorders (depression, mania), schizophrenic disorders, dementia, personality and behavioural disorders. Results: 31 (22%) were normal. 111 (78%) had varying degrees of ischaemia, infarction and cerebral/cerebellar atrophy.7 (4.9%) had space-occupying lesions which included two gliomas and five meningiomas. There were two chronic subdural haematomas and one arteriovenous malformation. Conclusion: 1. In our series, pathologic findings in 'routine' brain CT's were encountered in 78%. 2. The incidence of brain tumours was 4.9%, compared with 0.00005% of the general population. 3. CT scanning in psychiatric patients is cost-effective and especially indicated when there is an atypical presentation, or inadequate response to standard treatment.",adult;aged;article;brain tumor;computer assisted tomography;controlled study;female;human;major clinical study;male;mental patient;neurologic examination;radiodiagnosis;symptomatology;treatment indication;vascular disease,"Pickuth, D.;Heywang-Köbrunner, S. H.;Spielmann, R. P.",1999,,,0,
1929,"[Routine skull CT in psychiatric diagnosis] ""Routine""-Schadel-CT in der psychiatrischen Diagnostik","PURPOSE: To prospectively assess the spectrum of brain CT findings in psychiatric patients and to determine the number of patients that had an underlying cause for the symptoms. PATIENTS AND METHODS: Over a period of six months, 142 patients (78 males, 64 females; median age 61 [18-91] years) were referred for CT brain scans. Their scans were reviewed, along with the clinical information that was provided in the request form. All the hard copies were reviewed to assess areas of ischaemia, infarction, atrophy, tumours, and haematomas. The majority of requests were to exclude vascular event or space-occupying lesions. Clinical indications included mood disorders (depression, mania), schizophrenic disorders, dementia, personality and behavioural disorders. RESULTS: 31 (22%) were normal. 111 (78%) had varying degrees of ischaemia, infarction and cerebral/cerebellar atrophy. 7 (4.9%) had space-occupying lesions which included two gliomas and five meningiomas. There were two chronic subdural haematomas and one arteriovenous malformation. CONCLUSION: 1. In our series, pathologic findings in ""routine"" brain CT's were encountered in 78%. 2. The incidence of brain tumours was 4.9%, compared with 0.00005% of the general population. 3. CT scanning in psychiatric patients is cost-effective and especially indicated when there is an atypical presentation, or inadequate response to standard treatment.","0 (Contrast Media);Adolescent;Adult;Aged;Aged, 80 and over;Brain/diagnostic imaging;Contrast Media;Diagnosis, Differential;Diagnostic Tests, Routine/instrumentation/methods;Female;Humans;Male;Middle Aged;Neurocognitive Disorders/ diagnostic imaging;Prospective Studies;Skull/ diagnostic imaging;Tomography, X-Ray Computed/instrumentation/methods","Pickuth, D.;Heywang-Kobrunner, S. H.;Spielmann, R. P.",1999,Nov,,0,
1930,[Routine skull CT in psychiatric diagnosis],"PURPOSE: To prospectively assess the spectrum of brain CT findings in psychiatric patients and to determine the number of patients that had an underlying cause for the symptoms. PATIENTS AND METHODS: Over a period of six months, 142 patients (78 males, 64 females; median age 61 [18-91] years) were referred for CT brain scans. Their scans were reviewed, along with the clinical information that was provided in the request form. All the hard copies were reviewed to assess areas of ischaemia, infarction, atrophy, tumours, and haematomas. The majority of requests were to exclude vascular event or space-occupying lesions. Clinical indications included mood disorders (depression, mania), schizophrenic disorders, dementia, personality and behavioural disorders. RESULTS: 31 (22%) were normal. 111 (78%) had varying degrees of ischaemia, infarction and cerebral/cerebellar atrophy. 7 (4.9%) had space-occupying lesions which included two gliomas and five meningiomas. There were two chronic subdural haematomas and one arteriovenous malformation. CONCLUSION: 1. In our series, pathologic findings in ""routine"" brain CT's were encountered in 78%. 2. The incidence of brain tumours was 4.9%, compared with 0.00005% of the general population. 3. CT scanning in psychiatric patients is cost-effective and especially indicated when there is an atypical presentation, or inadequate response to standard treatment.","Adolescent;Adult;Aged;Aged, 80 and over;Brain/radiography;Contrast Media;Diagnosis, Differential;*Diagnostic Tests, Routine/instrumentation/methods;Female;Humans;Male;Middle Aged;Neurocognitive Disorders/*radiography;Prospective Studies;Skull/*radiography;*Tomography, X-Ray Computed/instrumentation/methods","Pickuth, D.;Heywang-Kobrunner, S. H.;Spielmann, R. P.",1999,Nov,,0,
1931,SPECT and FDG-PET in diagnostics of neurolues,"Syphilis is a recurrent treponematosis of acute and chronic evolution. In general it is either sexually or congenitally transmitted. Primary syphilis appears as a single and painless lesion. Secondary syphilis may manifest years later, the secondary bacteremic stage is accompanied by generalized mucocutaneous lesions. Tertiary disease can be disseminated to bones and virtually any organ, involving principally the ascending aorta and the central nervous system. Nuclear medicine provides diagnostic methods in case of skeletal manifestations by bone scan - identifying periostitis and osteomyelitis. Hepatic gummas can be imaged by 99m-Tc-colloid liver scintigraphy. In neurosyphilis brain perfusion SPECT enables imaging of cerebral involvement by small vessel endarteritis resulting from syphilitic vascular disease. 18-FDG PET is also useful to evaluate neurosyphilis, a reduction of brain glucose consumption is observed. The technique adequately enables imaging of therapeutic response and might be superior to morphologic imaging. We present our experiences with these nuclear medicine methods in patients with neurolues. The incidence of neurolues is estimated at 2 per 100.000 inhabitants worldwide, migration processes might bring a re-emergence of this disease to Austria and other developed countries of the EU. Scintigraphic methods should be kept in mind for diagnostic evaluation of neurosyphilis. © 2008 Springer-Verlag.",,"Pichler, R.;Doppler, S.;Szalay, E.;Hertl, C.;Knell, U.;Winkler, J.",2008,October,,0,
1932,Increased QT variability in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: Although sudden death (SD) accounts for numerous cases of premature mortality in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the risk factors responsible for this dramatic event remain unclear. We sought possible differences in the QT variability index (QTVI) -- a well-known index of temporal dispersion in myocardial repolarization strongly associated with the risk of SD -- between a group of patients with CADASIL and healthy controls. METHODS: A total of 13 patients with CADASIL and 13 healthy volunteers underwent a 5-min electrocardiogram recording to calculate the QTVI. All the patients also underwent a clinical assessment, including functional status by Rankin score, and a magnetic resonance imaging (MRI) brain scan for quantitative analysis of T2-weighted (T2-W) and T1-weighted (T1-W) lesion volume (LV). RESULTS: Short-term QT-interval analysis showed significantly higher QTVI (P = 0.029) in patients than in controls. In patients, notwithstanding the limitations of the small sample size, QTVI also well correlated with T1-W LV (r = 0.747, P = 0.003) and T2-W LV (r = 0.731, P = 0.005). CONCLUSION: Because patients with CADASIL have increased temporal cardiac repolarization variability as assessed by QTVI, this mechanism could underlie these patients' risk of SD. Whether this easily assessed, non-invasive marker could be used to stratify the risk of malignant ventricular arrhythmias in patients with CADASIL and, possibly, to guide their therapeutic management warrants confirmation from larger prospective studies.","Adult;Aged;Arrhythmias, Cardiac/diagnosis/ etiology/physiopathology;Brain/blood supply/pathology/physiopathology;CADASIL/ complications;Cerebral Arteries/pathology;Death, Sudden, Cardiac/ etiology;Electrocardiography;Female;Heart Conduction System/physiopathology;Heart Rate/physiology;Heart Ventricles/innervation/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Pilot Projects;Predictive Value of Tests","Piccirillo, G.;Magri, D.;Mitra, M.;Rufa, A.;Zicari, E.;Stromillo, M. L.;De Stefano, N.;Dotti, M. T.",2008,Nov,10.1111/j.1468-1331.2008.02300.x,0,
1933,Anti-amyloid beta autoantibodies in cerebral amyloid angiopathy-related inflammation: implications for amyloid-modifying therapies,"OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid-related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti-amyloid beta (Abeta) autoantibodies in the acute and remission phases of CAA-ri. METHODS: We used a novel ultrasensitive technique on patients from a retrospective multicenter case-control study, and evaluated the anti-Abeta autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA-ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Abeta40, Abeta42, tau, P-181 tau, and APOE genotype were also investigated. RESULTS: During the acute phase of CAA-ri, anti-Abeta autoantibodies were specifically increased and directly correlated with Abeta mobilization, together with augmented tau and P-181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Abeta and axonal degeneration markers decreased in parallel. INTERPRETATION: Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Abeta, directly related to autoantibody concentration and soluble Abeta. The CSF dosage of anti-Abeta autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Abeta autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.",Adult;Aged;Amyloid beta-Peptides/ cerebrospinal fluid/immunology;Apolipoproteins E/genetics;Autoantibodies/ cerebrospinal fluid;Brain/pathology;Case-Control Studies;Cerebral Amyloid Angiopathy/cerebrospinal fluid/complications/immunology;Female;Humans;Inflammation/cerebrospinal fluid/etiology/immunology;Male;Middle Aged;Peptide Fragments/cerebrospinal fluid;Phosphorylation;Retrospective Studies;Steroids/therapeutic use;tau Proteins/cerebrospinal fluid,"Piazza, F.;Greenberg, S. M.;Savoiardo, M.;Gardinetti, M.;Chiapparini, L.;Raicher, I.;Nitrini, R.;Sakaguchi, H.;Brioschi, M.;Billo, G.;Colombo, A.;Lanzani, F.;Piscosquito, G.;Carriero, M. R.;Giaccone, G.;Tagliavini, F.;Ferrarese, C.;DiFrancesco, J. C.",2013,Apr,10.1002/ana.23857,0,
1934,"Sporadic four-repeat tauopathy with frontotemporal degeneration, parkinsonism and motor neuron disease","We report a sporadic tauopathy of 6-year duration in a 76-year-old woman. Her initial symptoms were asymmetrical parkinsonism and muscle weakness, with apraxia appearing 2 years later. The brain showed frontal and temporal cerebral atrophy; severe neuronal loss and gliosis were observed in the precentral cortex (loss of Betz cells was also evident) and premotor area, and in the medial temporal lobe, including the temporal tip, amygdala, and hippocampal CA1-subiculum border zone. The substantia nigra showed moderate neuronal loss and gliosis. In the spinal cord, loss of the anterior horn cells and degeneration of the corticospinal tracts were a characteristic feature. In addition, in the affected regions, the remaining neurons were often found to contain intracytoplasmic inclusions resembling neurofibrillary tangles. Tau immunostaining revealed widespread glial-predominant lesions in the cerebral gray and white matter. In contrast, predominance of neuronal lesions (pretangles/tangles) was a feature in the subcortical gray matter, including the spinal cord. The remaining upper and lower motor neurons were also affected by tau pathology. Accumulated tau in these glial cells and neurons was clearly recognized by a specific antibody against four-repeat (4R) tau. The ultrastructural presence of tau-positive tubular structures was confirmed in the glial cells and neurons (tangles). Immunoblotting of a frozen frontal lobe sample revealed accumulation of 4R-predominant tau isoforms. No mutations were found in the tau gene. These findings indicate that a sporadic 4R tauopathy can cause frontotemporal degeneration, parkinsonism, and motor neuron disease. The present case could represent a new clinicopathological phenotype of non-familial tauopathy. © Springer-Verlag 2005.",levodopa;protein antibody;tau protein;aged;amygdaloid nucleus;anterior horn cell;article;brain atrophy;brain degeneration;case report;cell inclusion;clinical feature;death;disease duration;disease severity;female;frontal lobe;gene mutation;glia cell;gliosis;gray matter;hippocampus;human;human tissue;immunoblotting;immunohistochemistry;motor neuron disease;neurofibrillary tangle;nuclear magnetic resonance imaging;parkinsonism;phenotype;priority journal;pyramidal nerve cell;pyramidal tract;spinal cord;subiculum;substantia nigra;tauopathy;temporal lobe;ultrastructure;white matter,"Piao, Y. S.;Tan, C. F.;Iwanaga, K.;Kakita, A.;Takano, H.;Nishizawa, M.;Lashley, T.;Revesz, T.;Lees, A.;de Silva, R.;Tsujihata, M.;Takahashi, H.",2005,,,0,
1935,Major superficial white matter abnormalities in Huntington's disease,"Background: The late myelinating superficial white matter at the juncture of the cortical gray and white matter comprising the intracortical myelin and short-range association fibers has not received attention in Huntington's disease. It is an area of the brain that is late myelinating and is sensitive to both normal aging and neurodegenerative disease effects. Therefore, it may be sensitive to Huntington's disease processes. Methods: Structural MRI data from 25 Pre-symptomatic subjects, 24 Huntington's disease patients and 49 healthy controls was run through a cortical pattern-matching program. The surface corresponding to the white matter directly below the cortical gray matter was then extracted. Individual subject's Diffusion Tensor Imaging (DTI) data was aligned to their structural MRI data. Diffusivity values along the white matter surface were then sampled at each vertex point. DTI measures with high spatial resolution across the superficial white matter surface were then analyzed with the General Linear Model to test for the effects of disease. Results: There was an overall increase in the axial and radial diffusivity across much of the superficial white matter (p < 0.001) in Pre-symptomatic subjects compared to controls. In Huntington's disease patients increased diffusivity covered essentially the whole brain (p < 0.001). Changes are correlated with genotype (CAG repeat number) and disease burden (p < 0.001). Conclusions: This study showed broad abnormalities in superficial white matter even before symptoms are present in Huntington's disease. Since, the superficial white matter has a unique microstructure and function these abnormalities suggest it plays an important role in the disease.",adult;article;CAG repeat;clinical article;controlled study;correlation analysis;diffusion tensor imaging;disease classification;disease course;disease severity;female;fractional anisotropy;functional status;genotype;human;Huntington chorea;image analysis;male;Mini Mental State Examination;myelination;neuroimaging;nuclear magnetic resonance imaging;white matter lesion,"Phillips, O. R.;Joshi, S. H.;Squitieri, F.;Sanchez-Castaneda, C.;Narr, K.;Shattuck, D. W.;Caltagirone, C.;Sabatini, U.;Di Paola, M.",2016,,,0,
1936,The superficial white matter in Alzheimer's disease,"White matter abnormalities have been shown in the large deep fibers of Alzheimer's disease patients. However, the late myelinating superficial white matter comprised of intracortical myelin and short-range association fibers has not received much attention. To investigate this area, we extracted a surface corresponding to the superficial white matter beneath the cortex and then applied a cortical pattern-matching approach which allowed us to register and subsequently sample diffusivity along thousands of points at the interface between the gray matter and white matter in 44 patients with Alzheimer's disease (Age: 71.02±5.84, 16M/28F) and 47 healthy controls (Age 69.23±4.45, 19M/28F). In patients we found an overall increase in the axial and radial diffusivity across most of the superficial white matter (P<0.001) with increases in diffusivity of more than 20% in the bilateral parahippocampal regions and the temporal and frontal lobes. Furthermore, diffusivity correlated with the cognitive deficits measured by the Mini-Mental State Examination scores (P<0.001). The superficial white matter has a unique microstructure and is critical for the integration of multimodal information during brain maturation and aging. Here we show that there are major abnormalities in patients and the deterioration of these fibers relates to clinical symptoms in Alzheimer's disease.",aged;aging;Alzheimer disease;angular gyrus;article;brain analysis;brain mapping;brain maturation;clinical article;clinical feature;cognitive defect;controlled study;corpus callosum;diffusion;diffusion weighted imaging;dorsolateral prefrontal cortex;female;fractional anisotropy;frontal lobe;functional neuroimaging;fusiform gyrus;gray matter;human;image analysis;insula;left hemisphere;limbic cortex;male;middle temporal gyrus;Mini Mental State Examination;motor cortex;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;occipital lobe;parahippocampal gyrus;parietal lobe;priority journal;radiological parameters;right hemisphere;superior temporal gyrus;temporal lobe;white matter;white matter structure;3T Allegra,"Phillips, O. R.;Joshi, S. H.;Piras, F.;Orfei, M. D.;Iorio, M.;Narr, K. L.;Shattuck, D. W.;Caltagirone, C.;Spalletta, G.;Di Paola, M.",2016,,,0,
1937,The Corticospinal Tract in Huntington's Disease,"Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T2*-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the ""dying back"" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.","Adult;Analysis of Variance;Female;Humans;Huntington Disease/*pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Motor Cortex/*pathology;Pyramidal Tracts/*pathology;Spinal Cord/*pathology;Statistics as Topic;CAG repeats;DTI diffusion tensor imaging;Huntington's disease;corticospinal tract;structural connectivity;tractography","Phillips, O.;Squitieri, F.;Sanchez-Castaneda, C.;Elifani, F.;Griguoli, A.;Maglione, V.;Caltagirone, C.;Sabatini, U.;Di Paola, M.",2015,Sep,10.1093/cercor/bhu065,0,
1938,Deep white matter in Huntington's disease,"White matter (WM) abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using Magnetic Resonance Imaging (MRI). In the present study, we examined the microstructure of the long-range large deep WM tracts by applying two different MRI approaches: Diffusion Tensor Imaging (DTI) -based tractography, and T2*weighted (iron sensitive) imaging. We collected Pre-HD subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Results revealed increased axial (AD) and radial diffusivity (RD) and iron levels in Pre-HD subjects compared to controls. Fractional anisotropy decreased between the Pre-HD and HD phase and AD/RD increased and although impairment was pervasive in HD, degeneration occurred in a pattern in Pre-HD. Furthermore, iron levels dropped for HD patients. As increased iron levels are associated with remyelination, the data suggests that Pre-HD subjects attempt to repair damaged deep WM years before symptoms occur but this process fails with disease progression.",Adult;Case-Control Studies;Cerebrum/pathology;Demography;Diffusion Tensor Imaging;Female;Humans;Huntington Disease/ pathology;Male;Middle Aged;White Matter/ pathology,"Phillips, O.;Squitieri, F.;Sanchez-Castaneda, C.;Elifani, F.;Caltagirone, C.;Sabatini, U.;Di Paola, M.",2014,,10.1371/journal.pone.0109676,0,
1939,Tractography of the corpus callosum in Huntington's disease,"White matter abnormalities have been shown in presymptomatic and symptomatic Huntington's disease (HD) subjects using Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) methods. The largest white matter tract, the corpus callosum (CC), has been shown to be particularly vulnerable; however, little work has been done to investigate the regional specificity of tract abnormalities in the CC. Thus, this study examined the major callosal tracts by applying DTI-based tractography. Using TrackVis, a previously defined region of interest tractography method parcellating CC into seven major tracts based on target region was applied to 30 direction DTI data collected from 100 subjects: presymptomatic HD (Pre-HD) subjects (n=25), HD patients (n=25) and healthy control subjects (n=50). Tractography results showed decreased fractional anisotropy (FA) and increased radial diffusivity (RD) across broad regions of the CC in Pre-HD subjects. Similar though more severe deficits were seen in HD patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease Burden/CAG repeat length as well as motor (UHDRSI) and cognitive (URDRS2) assessments. These results add evidence that CC pathways are compromised prior to disease onset with possible demyelination occurring early in the disease and suggest that CAG repeat length is a contributing factor to connectivity deficits. Furthermore, disruption of these callosal pathways potentially contributes to the disturbances of motor and cognitive processing that characterize HD.",Adult;Case-Control Studies;Corpus Callosum/ pathology;Diffusion Tensor Imaging;Female;Humans;Huntington Disease/ pathology;Magnetic Resonance Imaging;Male;Middle Aged,"Phillips, O.;Sanchez-Castaneda, C.;Elifani, F.;Maglione, V.;Di Pardo, A.;Caltagirone, C.;Squitieri, F.;Sabatini, U.;Di Paola, M.",2013,,10.1371/journal.pone.0073280,0,
1940,CADASIL can mimic multiple sclerosis,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be confused with multiple sclerosis (MS). We report a man with a father diagnosed with MS via magnetic resonance imaging (MRI). The index patient was subsequently diagnosed with MS after MRI for evaluation of migraine headaches. Genetic testing confirmed the CADASIL diagnosis. CADASIL is characterized by a history of migraine headaches, mid-adult onset of progressive cerebrovascular disease, diffuse white matter changes, and dementia. The mutation involves the Notch3 gene which changes a codon for arginine to cysteine at amino acid position 90.",,"Phillips, C. D.;Zuckerman, S. J.;Medical Education, C.",2010,2010,,0,
1941,Positron computed tomography studies of cerebral glucose metabolism in man: theory and application in nuclear medicine,"The capability of positron computed tomography (PCT) to delineate the substructures of the brain and its facility for accurately measuring the local tissue radioactivity concentration allow the application of tracer kinetic models for the study of local cerebral function in man. This principle and an adaptation of the 14C-deoxyglucose (DG) model of Sokoloff et al. with 18F-2-fluoro-deoxy-D-glucose (FDG) is being used at UCLA. Brookhaven National Laboratory, University of Pennsylvania, NIH, and the Massachusetts General Hospital to determine the local cerebral glucose metabolic rate (LCMRGIc) in normal man at rest and during sensory activation and the changes that occur in patients with a variety of cerebral disorders. Kinetic studies with PCT have been employed to measure the rate constants of the model in different gray and white matter structures of the brain in both normal and ischemic states. The precision of the method in normals has been shown to be about +/- 5% for 1.5-2.0 sq cm regions of the brain. Studies in normals have yielded values for hemispheric CMRGIc that are in agreement with measurement using the Kety-Schmidt technique and LCMRGIc values in agreement with values in monkeys using DG autoradiography. Studies in volunteers subjected to visual and auditory stimulation are demonstrating the potential of this technique for investigating the human brain's response to different stimuli. STudies in patients with stroke show excellent correlation between the degree, extent, and particular structures involved and the clinical symptoms. The method consistently detected hypometabolism in cortical, thalamic, and striatal tissues that were dysfunctional due to deactivation or damage but which appeared normal on x-ray CT. Studies in patients with partial epilepsy have shown hypometabolic zones that highly correlated anatomically with interictal EEG spike foci and were associated with normal x-ray CT studies in 77% of the patients studied. The studies on epilepsy at UCLA have resulted in the integration of the LCMRGIc study into the clinical workup of patients with partial epilepsy that are candidates for surgical resection of their epileptogenic focus (effective June 1979). Studies on Huntington's chorea, Parkinson's disease, aphasia, dementia, schizophrenia, and tumors are in early stage of investigation but also are providing exciting new results. Further studies are needed to determine the role of the local function information obtained with the PCT-FDG method in elucidating the basic mechanism and the potential to aid in improving the approach to medical therapy.","Brain/*metabolism;Glucose/*metabolism;Humans;Mathematics;Models, Biological;Tomography, Emission-Computed/*methods","Phelps, M. E.",1981,Jan,,0,
1942,Structural simplexity of the brain,"Simplexity is an emerging concept that expresses a possible complementary relationship between complexity and simplicity. The brain has been known as the most complex structure, and tremendous effort has been spent to study how it works. By understanding complex function of the brain, one can hope to unravel the mystery of its diseases and its biological systems. We propose herein an entropy-based framework for analysis of complexity with a particular application to the study of white matter changes of the human brain. In this analysis, the proposed approach takes into account both morphological structure and image intensity values of MRI scans to construct the complexity profiles of the brain. It has been realized that the quantity and spatial distribution of white matter changes play an important role in cognitive decline (i.e. dementia) and other neuropsychiatric disorders (i.e. multiple sclerosis, depression) as well as in other dementia disorders such as Alzheimers disease. Thus, the results can be utilized as a tool for automated quantification and comparison of various spatial distributions and orientations of age-related white matter changes where manual analysis is difficult and leads to different sensitivities for the respective MRI-based information of the brain. © 2010 Elsevier B.V.",,"Pham, T. D.;Elfiqi, H. Z.;Knecht, S.;Wersching, H.;Baune, B. T.;Berger, K.",2010,April,,0,
1943,Cardiovascular characteristics and cerebral CT findings in subjects with psychomotor disadaptation syndrome,"Context: In previous years, we described the Psychomotor Disadaptation Syndrome (PDS) which associated backward disequilibrium, cautious gait and loss of motor abilities. Several of these clinical characteristics have been described in reports interested in patients with leukoaraiosis and/or subcortical dysfunction. Arteriosclerosis might be one of the main factors implicated in subcortical lesions. Objective: The aim of this study was to record cardiovascular risk factors and to provide cerebral CT scan findings in patients with PDS. We have chosen to compare patients showing PDS with Alzheimer's disease (AD) patients, because AD is characterised by mostly dominant cortical abnormalities, whereas PDS might be determined by subcortical lesions. Method: Patients were recruited in the Geriatric Medicine Departments of the University Hospitals of Dijon (Burgundy, France) and Strasbourg (Alsace, France). 73 PDS and 68 AD were evaluated. Results: Orthostatic hypotension was significantly more frequent for PDS (54% in centre 1 and 31% in centre 2) than for AD (6% in each centre). Whitematter lesions were significantly more severe for PDS than for AD. Ventricular enlargement was significantly more important for PDS than for AD. The correlation was significant between orthostatic hypotension and ventricular enlargement. Conclusions: PDS is usually associated with severe white matter lesions on CT scan. Orthostatic hypotension could play an important part in the pathogenesis of subcortical lesions in PDS.",aged;Alzheimer disease;article;brain cortex;brain injury;brain ventricle dilatation;cardiovascular risk;clinical feature;computer assisted tomography;controlled study;disease association;disease severity;female;human;major clinical study;male;orthostatic hypotension;pathogenesis;psychomotor disadaptation syndrome;psychomotor disorder;white matter,"Pfitzenmeyer, P.;Martin-Hunyadi, C.;Mourey, F.;Baudouin, N.;D'Athis, P.;Mischis-Troussard, C.",2002,,,0,
1944,Frontostriatal fiber bundle compromise in HIV infection without dementia,"BACKGROUND: Quantitative fiber tracking derived from diffusion tensor imaging (DTI) was used to determine whether white matter association, projection, or commissural tracts are affected in nondemented individuals with HIV infection and to identify the regional distribution of sparing and impairment of fiber systems. METHODS: DTI measured fractional anisotropy and diffusivity, quantified separately for longitudinal (lambdaL) diffusivity (index of axonal injury) and transverse (lambdaT) diffusivity (index of myelin injury), in 11 association and projection white matter tracts and six commissural tracts in 29 men and 13 women with HIV infection and 88 healthy, age-matched controls (42 men and 46 women). RESULTS: The total group of HIV-infected individuals had higher diffusivity (principally longitudinal) than controls in the posterior sectors of the corpus callosum, internal and external capsules, and superior cingulate bundles. High longitudinal diffusivity, indicative of axonal compromise, was especially prominent in posterior callosal sectors, fornix, and superior cingulate bundle in HIV with AIDS. Unmedicated patients had notably high transverse diffusivity, indicative of myelin compromise, in the occipital forceps, inferior cingulate bundle, and superior longitudinal fasciculus. Pontocerebellar projection fibers were resistant to HIV effects as were commissural fibers coursing through premotor and sensorimotor callosal sectors. CONCLUSION: This quantitative survey of brain fiber tract integrity indicates that even nondemented HIV patients can have neuroradiological evidence for damage to association and commissural tracts. These abnormalities were vulnerable to exacerbation with AIDS and possibly mitigated by HAART.","Acquired Immunodeficiency Syndrome/pathology;Adult;Anisotropy;Anti-HIV Agents/pharmacology;Brain Mapping/methods;Corpus Striatum/pathology;Dementia/etiology;Diffusion Magnetic Resonance Imaging/methods;Female;Frontal Lobe/ pathology;HIV Infections/drug therapy/ pathology/psychology/virology;Humans;Image Interpretation, Computer-Assisted/methods;Longitudinal Studies;Male;Middle Aged;Nerve Fibers, Myelinated/drug effects/ pathology;Neural Pathways/pathology;Peripheral Nervous System Diseases/virology;Socioeconomic Factors;Viral Load","Pfefferbaum, A.;Rosenbloom, M. J.;Rohlfing, T.;Kemper, C. A.;Deresinski, S.;Sullivan, E. V.",2009,Sep 24,10.1097/QAD.0b013e32832e77fe,0,
1945,Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: Synergistic white matter damage,"A substantial proportion of individuals infected with human immunodeficiency virus (HIV) also abuse alcohol. Given that each condition can disrupt brain structural integrity, with a predilection for white matter, we used MR diffusion tensor imaging (DTI) and quantitative fibre tracking to examine the separate and combined effects on the microstructure of the corpus callosum. Subjects were men and women with alcoholism alone (n = 87), HIV infection alone (n = 42), alcoholism and HIV infection comorbidity (n = 52) and non-affected controls (n = 88). The two alcoholism groups had similar lifetime alcohol consumption histories; the two HIV-infected groups had similar CD4+ counts and viral loads; all groups were matched in body mass index, and no participant was demented. Compared with controls, all patient groups had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in callosal regions and fibre bundles coursing through the genu and splenium, but these effects were only significant in the two groups with alcoholism, which exhibited 0.65-1.2 SD abnormalities in FA and MD. The callosal regions were differentially affected by alcoholism, with the genu more affected than the splenium, a pattern even more pronounced in the fibre tracks. When the HIV-infected groups were divided by disease severity defined as an acquired immunodeficiency syndrome (AIDS)-defining event or low CD4+ counts (<200) and alcoholism comorbidity, the HIV-infected subgroup with AIDS and alcoholism exhibited ∼2 SD FA and MD abnormalities in the callosal sectors and fibres, abnormalities that were more than twice the effect sizes observed in the other three HIV-infected subgroups. Degradation of the callosal microstructure was consistently associated with alcoholism, with evidence for compounded alcoholism-HIV effects. Functional relevance of the microstructural abnormalities was supported by associations between motor deficits and low FA or high MD within the diagnostic groups. The high prevalence of alcoholism in HIV-infected individuals and the interfering effect of alcohol on HIV pharmacological response and therapy compliance underscore the need to recognize the independent and synergistic contributions of each condition to brain structure and function. © 2006 The Author(s).",,"Pfefferbaum, A.;Rosenbloom, M. J.;Adalsteinsson, E.;Sullivan, E. V.",2007,January,,0,
1946,"Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking","Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.","Adolescent;Adolescent Development/drug effects;Alcohol Drinking/ pathology;Cerebral Cortex/diagnostic imaging/drug effects/ growth & development;Child;Cohort Studies;Cross-Sectional Studies;Ethnic Groups;Female;Gray Matter/diagnostic imaging/drug effects/growth & development;Humans;Image Processing, Computer-Assisted;Incidental Findings;Magnetic Resonance Imaging;Male;Organ Size;Puberty;Sex Characteristics;White Matter/diagnostic imaging/drug effects/ growth & development;Young Adult;adolescence;cortex;development;ethnicity;sex","Pfefferbaum, A.;Rohlfing, T.;Pohl, K. M.;Lane, B.;Chu, W.;Kwon, D.;Nolan Nichols, B.;Brown, S. A.;Tapert, S. F.;Cummins, K.;Thompson, W. K.;Brumback, T.;Meloy, M. J.;Jernigan, T. L.;Dale, A.;Colrain, I. M.;Baker, F. C.;Prouty, D.;De Bellis, M. D.;Voyvodic, J. T.;Clark, D. B.;Luna, B.;Chung, T.;Nagel, B. J.;Sullivan, E. V.",2016,Oct,,0,1947
1947,"Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking","Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.",,"Pfefferbaum, A.;Rohlfing, T.;Pohl, K. M.;Lane, B.;Chu, W.;Kwon, D.;Nolan Nichols, B.;Brown, S. A.;Tapert, S. F.;Cummins, K.;Thompson, W. K.;Brumback, T.;Meloy, M. J.;Jernigan, T. L.;Dale, A.;Colrain, I. M.;Baker, F. C.;Prouty, D.;De Bellis, M. D.;Voyvodic, J. T.;Clark, D. B.;Luna, B.;Chung, T.;Nagel, B. J.;Sullivan, E. V.",2015,Sep 26,10.1093/cercor/bhv205,0,
1948,"In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease","BACKGROUND: Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging. OBJECTIVE: To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation. METHOD: Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectroscopic imaging and memory and language testing. RESULTS: Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD. CONCLUSION: Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.",Adult;Age Factors;Aged;Alzheimer Disease/ diagnosis/ metabolism/psychology;Cerebral Cortex/anatomy & histology/chemistry/ metabolism;Choline/ metabolism;Creatine/ metabolism;Female;Humans;Magnetic Resonance Spectroscopy;Male;Memory;Middle Aged;Neuropsychological Tests;Phosphocreatine/ metabolism,"Pfefferbaum, A.;Adalsteinsson, E.;Spielman, D.;Sullivan, E. V.;Lim, K. O.",1999,Feb,,0,
1949,"Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study","BACKGROUND: Microbleeds are hemosiderin deposits around small vessels and are well visualized with T2*-weighted gradient-recalled echo (GRE) imaging. OBJECTIVES: To determine frequency and topography of microbleeds in Alzheimer disease (AD) and to assess their association with leukoaraiosis and cognition. DESIGN: Case-control cross-sectional analysis. Microbleeds were counted using GRE imaging. Leukoaraiosis was rated on T2-weighted and proton density-weighted scans using the Age-Related White Matter Changes Rating Scale (ARWMC). Neuropsychological tests indexed cognition. SETTING: The Cognitive Neurology Clinic, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. PATIENTS: Individuals with probable AD (n = 80) and healthy controls (n = 25) from a longitudinal cohort with GRE sequences as part of standard imaging protocol (2002-2006). RESULTS: Microbleeds occurred in 29% of patients with AD and 12% of controls and were multiple (> 1) in 48% of patients with AD and 33% of controls. There was lobar (vs centrencephalic) predominance in 92% of AD patients, with occipital lobes accounting for 57% of these microbleeds. The ARWMC scores (P < .005) were significantly higher in AD patients with microbleeds than in those without, and microbleeds correlated with total (r = 0.39, P = .01) and parietooccipital (r = 0.28, P < .01) ARWMC scores. We were unable to demonstrate an association between microbleeds (or leukoaraiosis) and cognitive performance. CONCLUSIONS: Occipital predominance of microbleeds with corresponding parietooccipital leukoaraiosis has not been well described in prior imaging studies of AD. Microbleeds were frequent, often multiple, and predicted greater leukoaraiosis. These findings illustrate the complexity of AD vasculopathy and the need for additional studies in dementia and stroke populations.","Aged;Alzheimer Disease/complications/diagnosis/ physiopathology;Brain Mapping/methods;Case-Control Studies;Cognition/ physiology;Cross-Sectional Studies;Dementia/complications/diagnosis/physiopathology;Diagnosis, Differential;Female;Humans;Intracranial Hemorrhages/complications/diagnosis/ physiopathology;Leukoaraiosis/complications/diagnosis/ physiopathology;Male;Microcirculation/physiology;Neuropsychological Tests;Occipital Lobe/blood supply/pathology/physiology;Ontario","Pettersen, J. A.;Sathiyamoorthy, G.;Gao, F. Q.;Szilagyi, G.;Nadkarni, N. K.;St George-Hyslop, P.;Rogaeva, E.;Black, S. E.",2008,Jun,10.1001/archneur.65.6.790,0,
1950,CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis,"Objective: To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Methods: Case report with neuroimaging and pathologic data. Results: A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. Conclusions: The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity.",amyloid precursor protein;acute disease;adult;arterial wall thickening;article;artificial ventilation;autopsy;blood pressure regulation;brain hypoxia;brain infarction;CADASIL;case report;cerebellar peduncle;collagen disease;corona radiata (brain);diffuse axonal injury;disease exacerbation;femur fracture;gene;gene mutation;genetic screening;gray matter;heterozygosity;human;human tissue;hypotension;immunohistochemistry;intubation;leukoaraiosis;leukoencephalopathy;male;mean arterial pressure;middle aged;missense mutation;neuroimaging;Notch3 gene;nuclear magnetic resonance imaging;periodic acid Schiff stain;priority journal;quadriplegia;skin biopsy;traffic accident;vein disease;white matter;white matter infarct,"Pettersen, J. A.;Keith, J.;Gao, F.;Spence, J. D.;Black, S. E.",2017,,10.1212/wnl.0000000000003717,0,
1951,An update on brain imaging in parkinsonian dementia,"Disturbances of cognition are frequent in Parkinson's disease (PD). Unlike severe loss of dopamine early in PD, extensive cholinergic losses have been consistently reported in PD with dementia. Cholinergic imaging suggests that basal forebrain cholinergic system degeneration appears early in PD and worsens with dementia development. Cortical cholinergic denervation is similar in PD with dementia and dementia with Lewy bodies, supporting a common disease spectrum, at least with respect to cholinergic pathology. Presence of cerebral amyloidopathy in the setting of parkinsonism may accelerate cognitive decline. Novel MRI techniques illustrate the widespread presence of neurodegeneration in PD with dementia, affecting white matter tracts and connectivity functions. This review will outline current concepts regarding dementia development in PD and discuss their correlation with functional and structural neuroimaging including PET and MRI.",,"Petrou, M.;Kotagal, V.;Bohnen, N. I.",2012,Apr,10.2217/iim.12.10,0,
1952,"Branch atheromatous disease: A clinically meaningful, yet unproven concept","Background: In 1989, Louis Caplan first used the term branch atheromatous disease (BAD) to describe an occlusion or stenosis at the origin of a deep penetrating artery of the brain, associated with a microatheroma or a junctional plaque, and leading to an internal capsule or pontine small infarct. BAD remained an understudied concept for decades. In recent years, the increasing diffusion of high-resolution magnetic resonance imaging (HRMRI) techniques brought new attention to the BAD debate. We have reviewed clinical studies dealing with BAD-related stroke checking whether a univocal definition of BAD existed, as well as to what extent were consistently associated clinical and imaging features reported. Summary: We conducted a search of the available literature published up to October 20, 2015 via PubMed using the following search terms: 'branch atheromatous disease,' 'intracranial branch atheromatous disease,' 'cerebral branch atheromatous disease,' combined with 'stroke.' Forty-six articles were included. We found discrepant definitions and a large variation among clinical features reported in BAD-related stroke patients: among others, a consistent association between BAD and any specific vascular risk factor profile was not detected. Despite this, early neurological deterioration (END) was consistently reported to occur frequently in such patients, although no clear-cut rate range or specific predictor or mechanism of progression was established. In a majority of the studies reporting imaging data, BAD diagnosis was not based on the selective site or type of arterial walls changes, but was inferred based on the vascular territory, size and/or shape of the ischemic lesion. Following the concept that these changes are seated proximally along the perforator artery, differently from to lipohyalinosis changes located distally, the consequent ischemic lesion was hypothesized to be larger in BAD than in lacunar infarcts. However, across reviewed studies, there was little consistency on the dimensional cutoff used to define BAD-related infarcts. In the last few years, a still limited number of studies using HRMRI techniques is providing preliminary proofs that atheromatous changes causing selective remodeling in the parent vessel and extending through the proximal segment of perforating vessel may subtend BAD. Key Messages: Our literature search showed the lack of a clear-cut definition of BAD, although BAD-related strokes were consistently considered a high risk of END. The use of high-resolution imaging techniques in the assessment of small subcortical strokes may represent the cornerstone in the perspective to better delimiting the boundaries of BAD as a nosological entity.",,"Petrone, L.;Nannoni, S.;Del Bene, A.;Palumbo, V.;Inzitari, D.",2016,1,,0,
1953,Magnetic resonance microscopy and immunohistochemistry of the CNS of the mutant SOD murine model of ALS reveals widespread neural deficits,"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects motor neurons and descending motor tracts of the CNS. We have evaluated the CNS of a murine model of familial ALS based on the over-expression of mutant human superoxide dismutase (mSOD; G93A) using magnetic resonance microscopy (MRM) and immunohistochemistry (IHC). Three-dimensional volumetric analysis was performed from 3D T2*-weighted images acquired at 17.6 T at isotropic resolutions of 40 mum. Compared to controls, mSOD mice had significant reductions in the volumes of total brain, substantia nigra, striatum, hippocampus, and internal capsule, with decreased cortical thickness in primary motor and somatosensory cortices. In the spinal cord, mSOD mice had significantly decreased volume of both the total grey and white matter; in the latter case, the volume change was confined to the dorsal white matter. Increased apoptosis, GFAP positive astrocytes, and/or activated microglia were observed in all those CNS regions that showed volume loss except for the hippocampus. The MRM findings in mSOD over-expressing mice are similar to data previously obtained from a model of ALS-parkinsonism dementia complex (ALS-PDC), in which neural damage occurred following a diet of washed cycad flour containing various neurotoxins. The primary difference between the two models involves a significantly greater decrease in spinal cord white matter volume in mSOD mice, perhaps reflecting variations in degeneration of the descending motor tracts. The extent to which several CNS structures are impacted in both murine models of ALS argues for a reevaluation of the nature of the pathogenesis of ALS since CNS structures involved in Parkinson's and Alzheimer's diseases appear to be affected as well.","Amyotrophic Lateral Sclerosis/genetics/ pathology;Animals;Brain/metabolism/ pathology;Calcium-Binding Proteins/metabolism;Caspase 3/metabolism;Enzyme Activation;Glial Fibrillary Acidic Protein/metabolism;Immunohistochemistry;Mice;Mice, Transgenic;Microfilament Proteins;Microscopy;Mutation;Spinal Cord/metabolism/ pathology;Superoxide Dismutase/genetics/ metabolism","Petrik, M. S.;Wilson, J. M.;Grant, S. C.;Blackband, S. J.;Tabata, R. C.;Shan, X.;Krieger, C.;Shaw, C. A.",2007,,,0,
1954,Correlates of memory function in community-dwelling elderly: the importance of white matter hyperintensities,"We sought to identify magnetic resonance- (MR)-imaged structures associated with declarative memory in a community-dwelling sample of elderly Mexican-American individuals with a spectrum of cognitive decline. Measured structures were the hemispheric volumes of the hippocampus (HC), parahippocampal gyrus, and remaining temporal lobes, as well as severity of white matter signal hyperintensities (WMH). Participants were an imaged subsample from the Sacramento Area Latino Study of Aging (SALSA), N = 122. Individuals were categorized as normal, memory impaired (MI), cognitively impaired non-demented (CIND), or demented. We show that WMH was the strongest structural predictor for performance on a delayed free-recall task (episodic memory) in the entire sample. The association of WMH with delayed recall was most prominent in elderly normals and mildly cognitively impaired individuals with no dementia or impairment of daily function. However, the left HC was associated with verbal delayed recall only in people with dementia. The right HC volume predicted nonverbal semantic-memory performance. We conclude that WMH are an important pathological substrate that affects certain memory functions in normal individuals and those with mild memory loss and discuss how tasks associated with WMH may rely upon frontal lobe function.","Aged;Aged, 80 and over;Aging/ physiology;Brain/physiology;Dementia/pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Memory/ physiology;Memory Disorders/physiopathology;Mexican Americans;Middle Aged;Neuropsychological Tests;Regression Analysis;Residence Characteristics","Petkov, C. I.;Wu, C. C.;Eberling, J. L.;Mungas, D.;Zrelak, P. A.;Yonelinas, A. P.;Haan, M. N.;Jagust, W. J.",2004,May,10.1017/s1355617704103056,0,
1955,Neuroradiological findings in classical late infantile neuronal ceroid- lipofuscinosis,"We describe a girl aged 5 years, 6 months who began to have seizures at the age of 3 years, 9 months. A cranial CT scan revealed mild, generalized cerebral atrophy. During the next year, she gradually developed ataxia, myoclonic jerks, and bilateral optic nerve atrophy and lost motor skills. A second CT scan performed 12 months after the onset of first symptoms revealed marked progression of cerebral atrophy, especially in the infratentorial area. MRI demonstrated bilateral, periventricular hyperintensities in the T(2)-weighted images but no changes in the basal ganglia. Electron microscopic investigations of skin biopsies demonstrated curvilinear bodies, confirming the suspected diagnosis of late infantile neuronal ceroid-lipofuscinosis (LINCL). Predominance of cerebral atrophy in the infratentorial area is typical of LINCL. Periventricular white matter lesions may be evident on MRI scans of patients with classical and LINCL-variant disease. In contrast to neuroradiological findings in patients with LINCL-variant disease, findings in patients with classical LINCL revealed no changes in the basal ganglia.",,"Petersen, B.;Handwerker, M.;Huppertz, H. I.",1996,November,,0,
1956,Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL. METHOD: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points. RESULTS: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint. CONCLUSIONS: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.",Adult;Atrophy;Brain/ pathology;CADASIL/ pathology/psychology;Cognition Disorders/etiology;Comorbidity;Disease Progression;Female;Fibrinogen/analysis;Follow-Up Studies;Homocysteine/blood;Humans;Hypercholesterolemia/epidemiology;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size;Risk Factors;Smoking/epidemiology,"Peters, N.;Holtmannspotter, M.;Opherk, C.;Gschwendtner, A.;Herzog, J.;Samann, P.;Dichgans, M.",2006,May 23,10.1212/01.wnl.0000216271.96364.50,0,
1957,[Vascular dementia] Vaskulare Demenz,"Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.","0 (Cholinesterase Inhibitors);W8O17SJF3T (Memantine);Aged;Brain/pathology;CADASIL/diagnosis/epidemiology/etiology/therapy;Cholinesterase Inhibitors/therapeutic use;Cross-Sectional Studies;Dementia, Multi-Infarct/diagnosis/epidemiology/etiology/therapy;Dementia, Vascular/ diagnosis/epidemiology/etiology/therapy;Diagnosis, Differential;Humans;Interdisciplinary Communication;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Memantine/therapeutic use;Neuropsychological Tests;Patient Care Team;Population Dynamics;Practice Guidelines as Topic;Risk Factors;Stroke/diagnosis/epidemiology/etiology/therapy","Peters, N.;Dichgans, M.",2010,Oct,,0,
1958,[Vascular dementia],"Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.","Aged;Brain/pathology;CADASIL/diagnosis/epidemiology/etiology/therapy;Cholinesterase Inhibitors/therapeutic use;Cross-Sectional Studies;Dementia, Multi-Infarct/diagnosis/epidemiology/etiology/therapy;Dementia, Vascular/*diagnosis/epidemiology/etiology/therapy;Diagnosis, Differential;Humans;Interdisciplinary Communication;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Memantine/therapeutic use;Neuropsychological Tests;Patient Care Team;Population Dynamics;Practice Guidelines as Topic;Risk Factors;Stroke/diagnosis/epidemiology/etiology/therapy","Peters, N.;Dichgans, M.",2010,Oct,10.1007/s00115-009-2848-4,0,
1959,Predicting progression to dementia in elderly subjects with mild cognitive impairment using both cognitive and neuroimaging predictors,"The objective of this work was to assess the predictive accuracy of targeted neuroimaging and neuropsychological measures for the detection of incipient dementia in individuals with mild cognitive impairment (MCI), and to examine the potential benefit of combining both classes of measures. Baseline MRI measures included hippocampal volume, cortical thickness, and white matter hyperintensities. Neuropsychological assessment focused on different aspects of episodic memory (i.e., familiarity, free recall, and associative memory) and executive control functions (i.e., working memory, switching, and planning). Global and regional cortical thinning was observed in MCI patients who progressed to dementia compared to those who remained stable, whereas no differences were found between groups for baseline hippocampal volume and white matter hyperintensities. The strongest neuroimaging predictors were baseline cortical thickness in the right anterior cingulate and middle frontal gyri. For cognitive predictors, we found that deficits in both free recall and recognition episodic memory tasks were highly suggestive of progression to dementia. Cortical thinning in the right anterior cingulate gyrus, combined to controlled and familiarity-based retrieval deficits, achieved a classification accuracy of 87.5%, a specificity of 90.9%, and a sensitivity of 83.3%. This predictive model including both classes of measures provided more accurate predictions than those based on neuroimaging or cognitive measures alone. Overall, our findings suggest that detecting preclinical Alzheimer's disease is probably best accomplished by combining complementary information from targeted neuroimaging and cognitive classifiers, and highlight the importance of taking into account both structural and functional changes associated with the disease.","Aged;Association Learning;Attention;Cerebral Cortex/pathology;Dementia/*diagnosis/physiopathology;*Disease Progression;Executive Function;Female;Hippocampus/pathology;Humans;Longitudinal Studies;*Magnetic Resonance Imaging;Male;Memory, Short-Term;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/*physiopathology;*Neuropsychological Tests;Predictive Value of Tests;Alzheimer's disease;cortical thickness;episodic memory;mild cognitive impairment","Peters, F.;Villeneuve, S.;Belleville, S.",2014,,10.3233/jad-130842,0,
1960,Cerebellar arteriovenous malformation and vertebral artery aneurysm in a CADASIL patient,"The presence of large vessels malformations has not been reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We describe a CADASIL patient in whom a brain cerebellar arteriovenous malformation was revealed by magnetic resonance (MR) imaging. An MR angiogram documented also an aneurysm along the right intracranial vertebral artery at the junction with the posterior-inferior cerebellar artery. The aneurysm was successfully treated by means of endovascular coil embolization. No neurological complication occurred in our patient during the angiographic procedure. In this case, in addition to an incidental coexistence of CADASIL and large vessels abnormalities, a causal role of the Notch pathway alteration could be hypothesized. Dysregulation of the Notch pathway is linked to several human diseases besides CADASIL. In one of these (the Alagille syndrome) intracranial aneurysms are reported. This hypothesis contrasts however with the absence of similar reports in other CADASIL cases and needs corroboration in large series. © Blackwell Munksgaard 2006.",,"Pescini, F.;Sarti, C.;Pantoni, L.;Mangiafico, S.;Bianchi, S.;Dotti, M. T.;Federico, A.;Inzitari, D.",2006,January,,0,
1961,"Letter by Pescini et al regarding article, ""peripheral artery disease as a manifestation of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and practical implications""",,CADASIL;carotid artery;cognitive defect;dementia;diabetes mellitus;family history;femoral artery;genetic screening;hemisphere;human;hypercholesterolemia;iliac artery;letter;migraine;nuclear magnetic resonance imaging;peripheral occlusive artery disease;priority journal;kidney artery;risk factor;smoking;toe gangrene,"Pescini, F.;Poggesi, A.;Pantoni, L.",2013,,,0,
1962,Circulating Biomarkers in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease. METHODS: We assessed plasma levels of von Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49 CADASIL patients and 49 age-matched controls and their association with clinical/functional and neuroimaging features. RESULTS: In multivariate analysis, CADASIL patients had significantly higher vWF and lower EPC levels. TM levels were similar in the 2 groups. CADASIL patients with a more severe clinical phenotype (history of stroke or dementia) presented lower CPC levels in comparison with patients with a milder phenotype. On correlation analysis, lower CPC levels were associated with worse performances on neuropsychological, motor and functional tests, and with higher lesion load on brain magnetic resonance imaging (degree of leukoencephalopathy and number of lacunar infarcts). CONCLUSIONS: This is the first CADASIL series in which multiple circulating biomarkers have been studied. Our findings support previous studies on the presence and the possible modulating effect of endothelial impairment in the disease. Furthermore, our research data suggest that blood CPCs may be markers of disease severity.",Cadasil;cerebral small vessel disease;circulating progenitor cells;endothelial impairment;von Willebrand factor,"Pescini, F.;Donnini, I.;Cesari, F.;Nannucci, S.;Valenti, R.;Rinnoci, V.;Poggesi, A.;Gori, A. M.;Giusti, B.;Rogolino, A.;Carluccio, A.;Bianchi, S.;Dotti, M. T.;Federico, A.;Balestrino, M.;Adriano, E.;Abbate, R.;Inzitari, D.;Pantoni, L.",2017,Apr,,0,
1963,A pathogenic mutation on exon 21 of the NOTCH3 gene causing CADASIL in an octogenarian paucisymptomatic patient,"CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an inherited small vessel disease causing migraine, early strokes, cognitive impairment and premature death. The disease is caused by NOTCH3 gene puntiform mutations on one of the exons coding for the epidermal-growth factor (EGF)-like repeats of the extracellular domain of the NOTCH3 receptor. Mutations have been reported with higher frequency on some exons, and never on 6 out of a total of 23. We report for the first time a mutation (c.3471C>G) on exon 21 of the NOTCH3 gene that leads to a cysteine substitution (p.1131C>W) in the EGF-like repeat 29 of the NOTCH3 receptor extracellular domain, and that is responsible for CADASIL in a functionally independent elderly man who came to our attention at the age of 79 because of a minor stroke. CADASIL suspicion aroused only from the finding of severe white matter changes extended to the temporopolar region on cerebral magnetic resonance imaging. This case report underlines that, when CADASIL is suspected, molecular analysis should be performed on all the NOTCH3 exons coding for EGF-like repeats and not be limited to those where mutations have been found with higher frequency, and that the disease may be encountered also in mildly symptomatic elderly patients. The newly reported mutation might sustain a milder expressivity of the disease. © 2007 Elsevier B.V. All rights reserved.",,"Pescini, F.;Bianchi, S.;Salvadori, E.;Poggesi, A.;Dotti, M. T.;Federico, A.;Inzitari, D.;Pantoni, L.",2008,15,,0,
1964,Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD?,"BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe. CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.",Aged;Alzheimer Disease/ genetics/ pathology;Apolipoprotein E4;Apolipoproteins E/ genetics;Brain/ pathology;Carrier State;Cognition/ physiology;Dementia/genetics;Health Status;Heterozygote Detection;Homozygote;Humans;Memory;Middle Aged;Reference Values;Risk Factors,"Persson, J.;Lind, J.;Larsson, A.;Ingvar, M.;Cruts, M.;Van Broeckhoven, C.;Adolfsson, R.;Nilsson, L. G.;Nyberg, L.",2006,Apr 11,10.1212/01.wnl.0000204180.25361.48,0,
1965,Clinical Correlation of Abnormal Findings on Magnetic Resonance Elastography in Idiopathic Normal Pressure Hydrocephalus,"BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible after ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. We studied iNPH patients using MRE prior to shunting, compared them with normal controls, and analyzed associations between MRE findings and clinical features, as a pilot assessment of MRE in iNPH. METHODS: Stiffness values were measured on preoperative MRE in 10 iNPH patients scheduled for VPS and compared with those in 20 age- and sex-matched controls. Stiffness results were correlated with clinical iNPH symptoms. RESULTS: MRE demonstrated significantly increased stiffness in iNPH in cerebrum (P = 0.04), occipital (P = 0.002), and parietal (P = 0.01) regions of interest (ROIs) and significantly decreased stiffness in periventricular ROIs (P < 0.0001). Stiffness was not significantly different in frontal (P = 0.1) and deep gray ROIs (P = 0.4). Univariate analysis showed associations between preoperative iNPH symptoms and abnormally increased stiffness, including urinary incontinence with cerebrum (P = 0.005), frontal (P = 0.04), and cerebellum (P = 0.03) ROIs, and Parkinsonism with occipital ROI (P = 0.04). Postoperative improvement was associated with increased deep gray stiffness (P = 0.01); failure was associated with increased temporal (P = 0.0002) stiffness. CONCLUSIONS: Based on the preliminary results of this small, limited analysis, brain stiffness may be altered in iNPH, and these alterations in parenchymal viscoelastic properties may be correlated with clinical symptoms. Increased temporal stiffness may predict surgical failure and potentially suggest an alternative dementing pathology underlying the iNPH-like symptoms. These findings highlight the potential future utility of MRE in iNPH management.",Idiopathic normal pressure hydrocephalus;Magnetic resonance elastography;Periventricular white matter,"Perry, A.;Graffeo, C. S.;Fattahi, N.;ElSheikh, M. M.;Cray, N.;Arani, A.;Ehman, R. L.;Glaser, K. J.;Manduca, A.;Meyer, F. B.;Huston, J., 3rd",2017,Mar,,0,
1966,PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins,"Background and Objectives: To study selective regional binding for tau pathology in vivo, using PET with [11C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy. Methods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [11C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region. Results: In comparison to the control group, PSP subjects showed specific uptake of [11C]PBB3 in putamen, midbrain, GP, and SN. Longer disease duration and more advanced clinical severity were generally associated with higher tracer retention. A DCTN1/PSP phenotype case showed increased binding in putamen, parietal lobe, and GP. In SNCA duplication carriers, there was a significant increase of [11C] PBB3 binding in GP, putamen, thalamus, ventral striatum, SN, and pedunculopontine nucleus. The MSA case showed increased binding in frontal lobe, GP, midbrain, parietal lobe, putamen, temporal lobe, SN, thalamus, and ventral striatum. Conclusions: All PSP patients showed increased retention of the tracer in the basal ganglia, as expected. Binding was also present in asymptomatic SNCA duplication carriers and in an MSA case, which are not typically associated with pathological tau deposition. This suggests the possibility that [11C]PBB3 binds to alpha-synuclein. © 2017 International Parkinson and Movement Disorder Society.",alpha synuclein;carbon 11;dynactin;tracer;aged;article;clinical article;controlled study;disease duration;frontal lobe;human;human tissue;male;mesencephalon;mutation;parietal lobe;pedunculopontine tegmental nucleus;phenotype;positron emission tomography;priority journal;putamen;tauopathy;temporal lobe;thalamus;ventral striatum,"Perez-Soriano, A.;Arena, J. E.;Dinelle, K.;Miao, Q.;McKenzie, J.;Neilson, N.;Puschmann, A.;Schaffer, P.;Shinotoh, H.;Smith-Forrester, J.;Shahinfard, E.;Vafai, N.;Wile, D.;Wszolek, Z.;Higuchi, M.;Sossi, V.;Stoessl, A. J.",2017,,10.1002/mds.27029,0,
1967,Delayed haemorrhage in the splenium of the corpus callosum after aneurysm rupture,"Background and object. Delayed haemorrhage in the splenium of the corpus callosum after aneurysm rupture is a rare finding. It can be defined as a haemorrhage not present at the initial diagnosis of subarachnoid bleeding, in the context of an aneurysm not located in the corpus callosum vascularization. Only three such cases have been reported, all with focal and circumscribed haematomas. We describe a case of diffuse haemorrhage along the splenium fibres. Patient. A 75-year-old woman was attended for an acute cognitive deterioration. Imaging studies revealed an aneurysm in the anterior communicating artery, and subacute haematomas in both frontal lobes. An uneventful surgical clipping of the aneurysm was performed. Postoperative CT-scans showed a haemorrhage along the splenium fibres, and hydrocephalus. A ventriculoperitoneal shunt was placed, and subsequent CT scans demonstrated progressive, spontaneous improvement of the splenium haemorrhage. Conclusions. Delayed haemorrhage in the splenium of the corpus callosum has a sporadic incidence. Physiopathology is unknown, and proposed explanations include compression of the splenium against the falx due to hydrocephalus, and haemorrhagic transformation of an ischaemic infarct due to vasospasm. Treatment is therefore based on adequate treatment of hydrocephalus and discontinuation of vasodilator drugs. The three previous cases of focal haematomas are discussed, and the first case of diffuse haemorrhage is described. © 2013 The Neurosurgical Foundation.",,"Pérez-Bovet, J.;Marnov, A.;Sanmillan Blasco, J. L.;Acebes Martín, J. J.",2013,December,,0,
1968,Cardiorespiratory fitness and white matter integrity in Alzheimer's disease,"The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A x D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.","Aged;Alzheimer Disease/ diagnostic imaging/ physiopathology;Cardiorespiratory Fitness;Cross-Sectional Studies;Diffusion Tensor Imaging;Exercise Test;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Sedentary Lifestyle;White Matter/ diagnostic imaging;Alzheimer's disease;Diffusion imaging;Exercise;Fitness;Neuroimaging","Perea, R. D.;Vidoni, E. D.;Morris, J. K.;Graves, R. S.;Burns, J. M.;Honea, R. A.",2016,Sep,,0,1969
1969,Cardiorespiratory fitness and white matter integrity in Alzheimer's disease,"The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A x D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.",,"Perea, R. D.;Vidoni, E. D.;Morris, J. K.;Graves, R. S.;Burns, J. M.;Honea, R. A.",2015,Aug 4,10.1007/s11682-015-9431-3,0,
1970,"A Comparative White Matter Study with Parkinson's disease, Parkinson's Disease with Dementia and Alzheimer's Disease","Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most common neurodegenerative disorders affecting older populations. AD is characterized by impaired memory and cognitive decline while the primary symptoms of PD include resting tremor, bradykinesia and rigidity. In PD, mild cognitive changes are frequently present, which could progress to dementia (PD dementia (PDD)). PDD and AD dementias are different in pathology although the difference in microstructural changes remains unknown. To further understand these diseases, it is essential to understand the distinct mechanism of their microstructural changes. We used diffusion tensor imaging (DTI) to investigate white matter tract differences between early stage individuals with AD (n=14), PD (n=12), PDD (n=9), and healthy non-demented controls (CON) (n=13). We used whole brain tract based spatial statistics (TBSS) and a region of interest (ROI) analysis focused on the substantia nigra (SN). We found that individuals with PDD had more widespread white matter degeneration compared to PD, AD, and CON. Individuals with AD had few regional abnormalities in the anterior and posterior projections of the corpus callosum while PD and CON did not appear to have significant white matter degeneration when compared to other groups. ROI analyses showed that PDD had the highest diffusivity in the SN and were significantly different from CON. There were no significant ROI differences between CON, PD, or AD. In conclusion, global white matter microstructural deterioration is evident in individuals with PDD, and DTI may provide a means with which to tease out pathological differences between AD and PD dementias.",,"Perea, R. D.;Rada, R. C.;Wilson, J.;Vidoni, E. D.;Morris, J. K.;Lyons, K. E.;Pahwa, R.;Burns, J. M.;Honea, R. A.",2013,Aug 26,10.4172/2161-0460.1000123,0,
1971,Cardiorespiratory fitness and brain volumes in men and women in the FINGER study,"Background: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). Methods: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. Results: in men, VO2peak was associated with cortical GM volume (beta = 0.56, P = 0.001) and total GM volume (beta = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. Conclusion: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.",Age Factors;Aged;Basal Ganglia/diagnostic imaging;Brain/ diagnostic imaging;Cardiorespiratory Fitness;Exercise Test;Female;Finland;Gray Matter/diagnostic imaging;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size;Oxygen Consumption;Predictive Value of Tests;Sex Factors;Temporal Lobe/diagnostic imaging;White Matter/diagnostic imaging;brain volume;cortical grey matter;older people;total grey matter,"Pentikainen, H.;Ngandu, T.;Liu, Y.;Savonen, K.;Komulainen, P.;Hallikainen, M.;Kivipelto, M.;Rauramaa, R.;Soininen, H.",2017,Mar 1,,0,1972
1972,Cardiorespiratory fitness and brain volumes in men and women in the FINGER study,"BACKGROUND: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). METHODS: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. RESULTS: in men, VO2peak was associated with cortical GM volume (beta = 0.56, P = 0.001) and total GM volume (beta = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. CONCLUSION: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.",brain volume;cardiorespiratory fitness;cortical grey matter;older people;total grey matter,"Pentikainen, H.;Ngandu, T.;Liu, Y.;Savonen, K.;Komulainen, P.;Hallikainen, M.;Kivipelto, M.;Rauramaa, R.;Soininen, H.",2017,Jan 06,,0,
1973,"Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48","Hereditary spastic paraplegias are a heterogeneous group of neurodegenerative disorders, clinically classified in pure and complex forms. Genetically, more than 70 different forms of spastic paraplegias have been characterized. A subgroup of complicate recessive forms has been distinguished for the presence of thin corpus callosum and white matter lesions at brain imaging. This group includes several genetic entities, but most of the cases are caused by mutations in the KIAA1840 (SPG11) and ZFYVE26 genes (SPG15). We studied a cohort of 61 consecutive patients with complicated spastic paraplegias, presenting at least one of the following features: mental retardation, thin corpus callosum and/or white matter lesions. DNA samples were screened for mutations in the SPG11/KIAA1840, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG48/AP5Z1 and SPG54/DDHD2 genes by direct sequencing. Sequence variants were found in 30 of 61 cases: 16 patients carried SPG11/KIAA1840 gene variants (26.2%), nine patients carried SPG15/ZFYVE26 variants (14.8%), three patients SPG35/FA2H (5%), and two patients carried SPG48/AP5Z1 gene variants (3%). Mean age at onset was similar in patients with SPG11 and with SPG15 (range 11-36), and the phenotype was mostly indistinguishable. Extrapyramidal signs were observed only in patients with SPG15, and epilepsy in three subjects with SPG11. Motor axonal neuropathy was found in 60% of cases with SPG11 and 70% of cases with SPG15. Subjects with SPG35 had intellectual impairment, spastic paraplegia, thin corpus callosum, white matter hyperintensities, and cerebellar atrophy. Two families had a late-onset presentation, and none had signs of brain iron accumulation. The patients with SPG48 were a 5-year-old child, homozygous for a missense SPG48/AP5Z1 variant, and a 51-year-old female, carrying two different nonsense variants. Both patients had intellectual deficits, thin corpus callosum and white matter lesions. None of the cases in our cohort carried mutations in the SPG21/ACP33 and SPG54/DDH2H genes. Our study confirms that the phenotype of patients with SPG11 and with SPG15 is homogeneous, whereas cases with SPG35 and with SPG48 cases present overlapping features, and a broader clinical spectrum. The large group of non-diagnosed subjects (51%) suggests further genetic heterogeneity. The observation of common clinical features in association with defects in different causative genes, suggest a general vulnerability of the corticospinal tract axons to a wide spectrum of cellular alterations. © 2014 The Author.",,"Pensato, V.;Castellotti, B.;Gellera, C.;Pareyson, D.;Ciano, C.;Nanetti, L.;Salsano, E.;Piscosquito, G.;Sarto, E.;Eoli, M.;Moroni, I.;Soliveri, P.;Lamperti, E.;Chiapparini, L.;Di Bella, D.;Taroni, F.;Mariotti, C.",2014,July,,0,
1974,Clinical and tomographic findings in vascular dementia,"Vascular dementia (VD) may arise as a sequel to any form of cerebrovascular disease. Since only some patients with cerebrovascular disease will eventually develop dementia, we studied the morphological and clinical findings associated with dementia in cerebrovascular patients. The relationship between these factors and the dementia syndrome was evaluated in 25 patients with VD, and 68 non demented subjects with a history of cerebral ischemic attacks. We found that VD was significantly associated with white matter lesions and atrophy on CT-scan, and a high prevalence of frontal lobe symptoms and signs.","Aged;Brain/physiopathology/radiography;Cerebrovascular Disorders/physiopathology/radiography;Dementia, Vascular/epidemiology/*physiopathology/*radiography;Female;Humans;Male;Middle Aged;Regression Analysis;Risk Factors;*Tomography, X-Ray Computed","Pennese, F.;Del Re, M. L.;Esposito, F.;Zito, M.;Abate, G.",1994,Feb,,0,
1975,The relationship of topographical memory performance to regional neurodegeneration in Alzheimer's disease,"The network activated during normal route learning shares considerable homology with the network of degeneration in the earliest symptomatic stages of Alzheimer's disease (AD). This inspired the virtual route learning test (VRLT) in which patients learn routes in a virtual reality environment. This study investigated the neural basis of VRLT performance in AD to test whether impairment was underpinned by a network or by the widely held explanation of hippocampal degeneration. VRLT score in a mild AD cohort was regressed against gray matter (GM) density and diffusion tensor metrics of white matter (WM) (n = 30), and, cerebral glucose metabolism (n = 26), using a mass univariate approach. GM density and cerebral metabolism were then submitted to a multivariate analysis [support vector regression (SVR)] to examine whether there was a network associated with task performance. Univariate analyses of GM density, metabolism and WM axial diffusion converged on the vicinity of the retrosplenial/posterior cingulate cortex, isthmus and, possibly, hippocampal tail. The multivariate analysis revealed a significant, right hemisphere-predominant, network level correlation with cerebral metabolism; this comprised areas common to both activation in normal route learning and early degeneration in AD (retrosplenial and lateral parietal cortices). It also identified right medio-dorsal thalamus (part of the limbic-diencephalic hypometabolic network of early AD) and right caudate nucleus (activated during normal route learning). These results offer strong evidence that topographical memory impairment in AD relates to damage across a network, in turn offering complimentary lesion evidence to previous studies in healthy volunteers for the neural basis of topographical memory. The results also emphasize that structures beyond the mesial temporal lobe (MTL) contribute to memory impairment in AD-it is too simplistic to view memory impairment in AD as a synonym for hippocampal degeneration.",Alzheimer's;Mri;Pet;multivariate;retrosplenial cortex;support vector;topographical memory,"Pengas, G.;Williams, G. B.;Acosta-Cabronero, J.;Ash, T. W.;Hong, Y. T.;Izquierdo-Garcia, D.;Fryer, T. D.;Hodges, J. R.;Nestor, P. J.",2012,,10.3389/fnagi.2012.00017,0,
1976,Transient cognitive impairment in TIA and minor stroke,"BACKGROUND AND PURPOSE: Acute cognitive impairment and delirium occur after major stroke and are associated with poor cognitive outcome. We conducted a population-based study to determine whether transient cognitive impairment (TCI) is seen acutely after cerebral transient ischemic attack (TIA) or minor stroke, and whether it predicts long-term cognitive decline. METHODS: Mini-mental-state examination was performed in consecutive testable patients with TIA or minor stroke (National Institutes of Health Stroke Scale </=3) seen acutely (1-7 days) in the Oxford Vascular Study (2002-2005) versus after 7 days, and in referrals seen acutely who had a subsequent noncerebrovascular diagnosis. We defined TCI as a baseline Mini-mental-state examination score >/=2 points below the 1-month follow-up score, and identified cognitive impairment (Montreal Cognitive Assessment [MoCA] <26/30) and severe dementia at 1-, 2-, and 5-year follow-up. RESULTS: In 280 TIA and minor stroke patients (mean age/SD 73.5/11.8 years), TCI was more frequent in those seen at 1 to 7 days (80/206; 38.9%) versus later (14/74; 19%; P=0.002) or in noncerebrovascular patients (10/47; 21%; P=0.004). TCI was associated with acute confusion (OR, 5.5; 95% CI, 2.5-11.7; P<0.0001), acute infarct on computed tomography (OR, 2.0; 1.2-3.5; P=0.01), and with residual focal deficits (OR,1.94; 1.13-3.34; P=0.01). However, it was still seen acutely in those whose focal deficits had resolved by time of assessment (41/120; 34%). Although patients with TCI had similar Mini-mental-state examination score by 1 month compared with those without TCI, their 5-year risks of cognitive impairment (OR, 4.3; 1.2-15.7; P=0.03) and severe dementia (OR, 4.9; 1.0-25.8; P=0.05) were increased. CONCLUSIONS: TCI is a manifestation of TIA and minor stroke, and may persist beyond resolution of focal symptoms. Our findings have implications for definitions in TIA and minor stroke and suggest that cognitive fragility may be revealed by minor cerebrovascular events.","Aged;Aged, 80 and over;Cohort Studies;Female;Follow-Up Studies;Humans;Ischemic Attack, Transient/*complications/diagnosis/*psychology;Male;Middle Aged;Mild Cognitive Impairment/diagnosis/*etiology/*psychology;Population Surveillance/methods;Prospective Studies;Stroke/*complications/diagnosis/*psychology","Pendlebury, S. T.;Wadling, S.;Silver, L. E.;Mehta, Z.;Rothwell, P. M.",2011,Nov,10.1161/strokeaha.111.621490,0,
1977,Is the SHRSP [corrected] strain a suitable model of spontaneous CADASIL?,"A number of features of the pathology occurring in spontaneously hypertensive stroke prone rats (SHRSPs), such as MRI brain signal abnormalities, the presence of high protein content in cerebrospinal fluid and vessel wall thickening, seem to indicate that this strain is a suitable model for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To explore this hypothesis, we sought the human diagnostic hallmarks of the disease [the accumulation of granular osmiophilic material (GOM) deposits in vessel walls and NOTCH3 gene mutations] in SHRSPs. Male SHRSPs fed a permissive diet were sacrificed 3 days after the first MRI visualisation of brain abnormalities. Whole blood and kidney samples were respectively collected for molecular and electron microscopy evaluations. Automated sequence analysis of exons and intron-exon boundaries did not reveal any genetic variation in the NOTCH3 gene, and electron microscopy excluded the presence of GOM. The findings of this study exclude SHRSPs as a possible model for CADASIL.","Animals;Brain/pathology;*CADASIL/genetics;Cytoplasmic Granules/chemistry/ultrastructure;*Disease Models, Animal;Genetic Predisposition to Disease;Glomerular Basement Membrane/chemistry/pathology;Humans;Hypertension/genetics/pathology;Magnetic Resonance Imaging;Male;Osmium Tetroxide;Proteinuria/genetics/pathology;Rats;Rats, Inbred SHR/*genetics;Rats, Mutant Strains/*genetics;Rats, Sprague-Dawley;Receptors, Notch/analysis/deficiency/genetics;Sodium Chloride, Dietary/toxicity;Staining and Labeling;Stroke/etiology/*genetics/pathology;Tunica Media/pathology","Penco, S.;Gelosa, P.;Pileggi, S.;Abbate, M.;Marocchi, A.;Guerrini, U.;Pignieri, A.;Tremoli, E.;Sironi, L.",2012,Feb,10.1007/s12031-011-9605-4,0,
1978,Is the SHRPS Strain a Suitable Model of Spontaneous CADASIL?,"A number of features of the pathology occurring in spontaneously hypertensive stroke prone rats (SHRSPs), such as MRI brain signal abnormalities, the presence of high protein content in cerebrospinal fluid and vessel wall thickening, seem to indicate that this strain is a suitable model for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To explore this hypothesis, we sought the human diagnostic hallmarks of the disease [the accumulation of granular osmiophilic material (GOM) deposits in vessel walls and NOTCH3 gene mutations] in SHRSPs. Male SHRSPs fed a permissive diet were sacrificed 3 days after the first MRI visualisation of brain abnormalities. Whole blood and kidney samples were respectively collected for molecular and electron microscopy evaluations. Automated sequence analysis of exons and intron-exon boundaries did not reveal any genetic variation in the NOTCH3 gene, and electron microscopy excluded the presence of GOM. The findings of this study exclude SHRSPs as a possible model for CADASIL. © 2011 Springer Science+Business Media, LLC.",osmium;CADASIL;model;animal model;nuclear magnetic resonance imaging;exon;brain;blood vessel wall;electron microscopy;pathology;cerebrospinal fluid;hypothesis;protein content;gene mutation;male;commercial phenomena;blood;kidney;sequence analysis;intron;genetic variability;gene;diagnosis;human;stroke prone spontaneously hypertensive rat;diet,"Penco, S.;Gelosa, P.;Pileggi, S.;Abbate, M.;Marocchi, A.;Guerrini, U.;Pignieri, A.;Tremoli, E.;Sironi, L.",2011,,,0,
1979,MRI and proton spectroscopy in children with late infantile neuronal ceroid lipofuscinosis: Preliminary results,"Aim of the study was to characterize findings on magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H-MRS) in children with late infantile neuronal ceroid lipofuscinosis (NCL) and the relationship between these results and duration of the disorder. Three children with late infantile NCL and six age-matched controls were examined with MRI and by localized (1)H-MRS. Voxel regions studied were periventricular frontal white matter, thalami and cerebellar deep white matter. N-acetylaspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratio was calculated. MRI showed various degrees of cortical atrophy and increased periventricular white matter signal intensity on T2- and -fluid attenuated inversion recovery-weighted images. There was no significant volume loss in the brainstem. Metabolic ratio (NAA/Cr and Cho/Cr) showed progressive decrease with longer disease duration in thalamic and cerebellar voxels and exhibited a negative relationship in frontal voxels. In conclusion, the most significant changes on neuroimaging in late infantile NCL are progressive cortical and cerebellar atrophy, which are more pronounced in the cerebellum. Decreased signal intensity in the thalami may also be observed as in other forms of NCL. (1)H-MRS is the most sensitive method for measuring metabolic changes. The decreased level of NAA although not specific, may still contribute significantly to the diagnosis of late infantile NCL. © 2007 IOS Press. All rights reserved.",,"Peǹa, J. A.;Cruz, E. M. L.;Leendertz, R.;Faneite, L. S.;Montiel-Nava, C.",2007,2007,,0,
1980,Structural differences in impaired verbal fluency in essential tremor patients compared to healthy controls,"Objective: We wanted to identify differences in grey and white matter in essential tremor patients compared to controls in the non-motor domain, using the example of impaired verbal fluency. Background: A disturbance of verbal fluency in essential tremor patients compared to healthy controls is behaviorally well described. Methods: Voxel-based morphometry and tract-based spatial statistics were used to analyze structural differences in grey and white matter in 19 essential tremor patients compared to 23 age- and gender-matched controls. Results: Several significant observations were made. (I) There was less grey matter in the predominantly right precuneus in the essential tremor group compared to controls [p <.001]. (II) In ET patients mean, axial, and radial diffusivity values broadly correlated with the tremor rating scale, pronounced in fronto-parietal regions [p <.05]. (III) In ET patients there was a significant decline in fractional anisotropy values in the corpus callosum in the correlation with verbal fluency results [p <.05]; by inclusion of the tremor rating scale as covariate of no interest this significance was however diminished to a tendency (p <.1). No significant results were found in these within-group correlations in grey matter analyses for ET patients (p >.05). Conclusion: The present results indicate that non-motor symptoms such as verbal fluency (VBF) in ET have a structural substrate; their reproduction requires the integration of potential environmental plasticity effects, differentiation into individual clinical subtypes and a careful handling with methodological peculiarities of structural MR imaging.",adult;article;Beck Depression Inventory;clinical article;controlled study;corpus callosum;dementia;diffusion weighted imaging;double blind procedure;essential tremor;female;finger tapping test;fluency disorder;fractional anisotropy;genetic susceptibility;gray matter;human;impaired verbal fluency;male;middle aged;mild cognitive impairment;neuropsychological test;nuclear magnetic resonance imaging;plasticity;precuneus;prefrontal cortex;priority journal;psychomotor performance;rating scale;tremor rating scale;voxel based morphometry;white matter,"Pelzer, E. A.;Nelles, C.;Pedrosa, D. J.;Eggers, C.;Burghaus, L.;Melzer, C.;Tittgemeyer, M.;Timmermann, L.",2017,,10.1002/brb3.722,0,
1981,Magnetic resonance imaging in Down's syndrome,"100% of brains of Down's adults over age 40 will show Alzheimer-type neuropathologic changes in the frontal and temporal lobes. In an attempt to image these lesions, magnetic resonance imaging (MRI) was performed in seven patients with Down's syndrome, ranging in age from 17 to 45 years, using a resistive unit operating at 0.15 Tesla. All scans were within normal limits except for one 45 year-old patient with severe left temporal lobe atrophy. No areas of abnormal signal were seen in the frontal or temporal lobes and the white matter lesions commonly seen in elderly demented subjects were not visualized in this group. We conclude that these white matter lesions are likely coincidental and not causally related to Alzheimer's changes. The pathologic process leading to the formation and development of Alzheimer's changes in the brains of Down's adults may not be visible on magnetic resonance images.",Adolescent;Adult;Atrophy;Brain/pathology;Down Syndrome/ pathology;Humans;Magnetic Resonance Spectroscopy;Middle Aged;Temporal Lobe/pathology,"Pelz, D. M.;Karlik, S. J.;Fox, A. J.;Vinuela, F.",1986,Nov,,0,
1982,Neuroradiological findings in the differential diagnosis of dementia in the elderly,"Alzheimer's disease (AD) and vascular dementia (VD) are the two main types of dementia. After the introduction of magnetic resonance (MR) as a routine diagnostic procedure, white matter hyperintensities and hippocampal atrophy have been demonstrated as the most relevant neuroradiological findings in old-age dementias. Since the clinical diagnosis of AD rests on probability criteria, these neuroradiological markers could represent positive indicators of disease, contributing to a more accurate differential diagnosis between AD and VD. Age-associated memory impairment (AAMI) is a controversial entity which is considered a normal manifestation of aging by some authors, while others rather believe it is an early, monosymptomatic phase of dementia; therefore, it is important to include this category when investigating dementia disorders. In the present study we carried out MR measurements of hippocampal volume and white matter hyperintensities in patients with AD, VD, AAMI and in healthy age-matched controls. Thirty-three consecutive patients entered the study. Twelve of them fulfilled the NINCDS-ADRDA criteria for probable AD. Nine patients fulfilled the NINDS-AIREN criteria for probable VD. A group of twelve subjects fulfilling Crook's et al. criteria for AAMI was also included. The control group consisted of nine healthy elderly subjects. All examinations were performed on a 1.5T unit. Hippocampal volumetry was carried out according to the method recently proposed by Pelliccioli and co-workers (1994). Signal hyperintensities were measured using a standard multi-echo/spin-echo technique and were scored in a semiquantitative way (Scheltens et Al., 1993). Hippocampal volumes were significantly reduced in AD and AAMI groups as compared to VD patients and controls, while no significant difference was found between AD and AAMI groups. As far as white matter hyperintensities are concerned, no significant difference among groups was observed in any of the periventricular hyperintensity (PVH) scores. White matter hyperintensities (WMH) showed statistically significant differences between VD and the other groups. Also basal ganglia hyperintensities (BGH) and infratentorial hyperintensity (ITH) total scores resulted higher in VD when compared to AD and controls. In order to establish the actual influence of age and disease in the hyperintensities scores, the analysis of covariance was applied using age as covariate. There was a definite effect of the pathological condition on WMH, age having no effect at all. The opposite was true for RVH scores. ITH proved to be prevalently influenced by disease while BGH mostly depended on age. Our findings indicate that hippocampal volume is significantly reduced in both AD and AAMI patients, but not in VD patients. As regards white matter hyperintensities, only patients with vascular dementia showed WMH scores significantly higher with respect to the other groups. No significant differences among groups were found for WMH scores. Our data support the view that hippocampal atrophy per se is a possible marker of AD and AAMI, while WMH in these conditions are present to the same extent as in age-matched controls. On the contrary, WMH consistently characterize vascular dementia, in the absence of a significant hippocampal atrophy. If confirmed in larger series, the combination of hippocampal volumetry and WMH might represent the neuroradiological diagnostic guidelines of AD and VD in a routine clinical setting. The exact definition of AAMI remains unsettled.",adult;aged;article;brain atrophy;clinical article;controlled study;dementia;differential diagnosis;female;hippocampus;human;male;nuclear magnetic resonance imaging;white matter,"Pelliccioli, G. P.;Parnetti, L.;Chiarini, P.;Floridi, P.;Campanella, S.;Guercini, G.;Leone, F.",1996,,,0,
1983,Two case reports of cerebral autosomal dominant arteriophaty with subcortical infarctions and leukoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) was first reported in European families and since 1993 it has been observed in America, Africa and Asia, suggesting that today the disease probably still remains largely underdiagnosed. CADASIL appears to be essentially a disorder of the arteries linked to single missense mutations in the Notch3 gene locus on chromosome 19; the aberrant dimerisation of Notch3, due to abnormal disulphide bridging with another Notch3 molecule or with another protein, may be involved in the pathogenesis of the disorder. It is characterized by recurrent stroke episodes and focal neurologic deficits progressing to pseudobulbar palsy and dementia, caused by multiple lacunar infarctions with ischemic and diffuse white matter abnormalities on neuroimaging. Migraine with aura, epileptic seizures and affective disorders are frequent additional symptoms of CADASIL. It is usually observed in the 3rd decade, but some individuals remain asymptomatic close to the age of 60.MRI displays a marked leukoencephalopathy in affected individuals as early as in the age of 20. The authors emphasize the role of a direct DNA test for gene mutation to make a differential diagnosis between CADASIL and other forms of vascular leukoencephalopathy as Alzheimer's dementia, multiple sclerosis and Binswanger's subcortical arteriopathic encephalopathy where CADASIL's arteriopathy is characterized by major alterations of vascular smooth muscle cells and the presence of specific granular osmiophilic deposits.",Notch receptor;adult;article;autosomal dominant disorder;brain infarction;case report;cerebral artery disease;chromosome 19;dementia;differential diagnosis;dimerization;disease course;female;gene locus;human;leukoencephalopathy;male;missense mutation;nuclear magnetic resonance imaging;symptomatology;vascular smooth muscle,"Pellicanò, S.;Costa, A.;Terra, L.",2001,,,0,
1984,Structural hippocampal network alterations during healthy aging: a multi-modal MRI study,"While hippocampal atrophy has been described during healthy aging, few studies have examined its relationship with the integrity of White Matter (WM) connecting tracts of the limbic system. This investigation examined WM structural damage specifically related to hippocampal atrophy in healthy aging subjects (n = 129), using morphological MRI to assess hippocampal volume and Diffusion Tensor Imaging (DTI) to assess WM integrity. Subjects with Mild Cognitive Impairment (MCI) or dementia were excluded from the analysis. In our sample, increasing age was significantly associated with reduced hippocampal volume and reduced Fractional Anisotropy (FA) at the level of the fornix and the cingulum bundle. The findings also demonstrate that hippocampal atrophy was specifically associated with reduced FA of the fornix bundle, but it was not related to alteration of the cingulum bundle. Our results indicate that the relationship between hippocampal atrophy and fornix FA values is not due to an independent effect of age on both structures. A recursive regression procedure was applied to evaluate sequential relationships between the alterations of these two brain structures. When both hippocampal atrophy and fornix FA values were included in the same model to predict age, fornix FA values remained significant whereas hippocampal atrophy was no longer significantly associated with age. According to this latter finding, hippocampal atrophy in healthy aging could be mediated by a loss of fornix connections. Structural alterations of this part of the limbic system, which have been associated with neurodegeneration in Alzheimer's disease, result at least in part from the aging process.",,"Pelletier, A.;Periot, O.;Dilharreguy, B.;Hiba, B.;Bordessoules, M.;Peres, K.;Amieva, H.;Dartigues, J. F.;Allard, M.;Catheline, G.",2013,,10.3389/fnagi.2013.00084,0,
1985,Mediterranean diet and preserved brain structural connectivity in older subjects,"INTRODUCTION: The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways). METHODS: We included 146 participants from the Bordeaux Three-City study nondemented when they completed a dietary questionnaire and who underwent a 3-T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging. RESULTS: In multivariate voxel-by-voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes. DISCUSSION: The MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research.",,"Pelletier, A.;Barul, C.;Feart, C.;Helmer, C.;Bernard, C.;Periot, O.;Dilharreguy, B.;Dartigues, J. F.;Allard, M.;Barberger-Gateau, P.;Catheline, G.;Samieri, C.",2015,Sep,10.1016/j.jalz.2015.06.1888,0,
1986,Frontotemporal neural systems supporting semantic processing in Alzheimer's disease,"We hypothesized that semantic memory for object concepts involves both representations of visual feature knowledge in modality-specific association cortex and heteromodal regions that are important for integrating and organizing this semantic knowledge so that it can be used in a flexible, contextually appropriate manner. We examined this hypothesis in an fMRI study of mild Alzheimer's disease (AD). Participants were presented with pairs of printed words and asked whether the words matched on a given visual-perceptual feature (e.g., guitar, violin: SHAPE). The stimuli probed natural kinds and manufactured objects, and the judgments involved shape or color. We found activation of bilateral ventral temporal cortex and left dorsolateral prefrontal cortex during semantic judgments, with AD patients showing less activation of these regions than healthy seniors. Moreover, AD patients showed less ventral temporal activation than did healthy seniors for manufactured objects, but not for natural kinds. We also used diffusion-weighted MRI of white matter to examine fractional anisotropy (FA). Patients with AD showed significantly reduced FA in the superior longitudinal fasciculus and inferior frontal-occipital fasciculus, which carry projections linking temporal and frontal regions of this semantic network. Our results are consistent with the hypothesis that semantic memory is supported in part by a large-scale neural network involving modality-specific association cortex, heteromodal association cortex, and projections between these regions. The semantic deficit in AD thus arises from gray matter disease that affects the representation of feature knowledge and processing its content, as well as white matter disease that interrupts the integrated functioning of this large-scale network.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/*physiopathology;Anisotropy;Brain/pathology/*physiopathology;Brain Mapping;Diffusion Magnetic Resonance Imaging;Female;Humans;Judgment/*physiology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology/physiology;Neuropsychological Tests;Pattern Recognition, Visual/*physiology;Photic Stimulation;Reading;Recognition (Psychology)/*physiology;*Semantics;Task Performance and Analysis","Peelle, J. E.;Powers, J.;Cook, P. A.;Smith, E. E.;Grossman, M.",2014,Mar,10.3758/s13415-013-0239-6,0,
1987,Reliability of the ABC/2 Method in Determining Acute Infarct Volume,"Background and Purpose: Infarct volume is used as a surrogate outcome measure in clinical trials of therapies for acute ischemic stroke. ABC/2 is a fast volumetric method, but its accuracy remains to be determined. We aimed to study the accuracy and reproducibility of ABC/2 in determining acute infarct volume with diffusion-weighted imaging. Methods: We studied 86 consecutive patients with acute ischemic stroke. Three blinded observers determined volume with the ABC/2 method, and the results were compared with those of the manual planimetric method. Results: The ABC/2 technique overestimated infarct volume by a median false increase (variable ABC/2 volume minus planimetric volume) of 7.33 cm(3) (1.29, 22.170, representing a 162.56% increase over the value of the gold standard (variable ABC/2 volume over planimetric volume) (121.70, 248.52). In each method, the interrater reliability was excellent: the intraclass correlations were .992 and .985 for the ABC/2 technique and planimetric method, respectively. Conclusions: ABC/2 is volumetric method with clinical value but it consistently overestimates the real infarct volume. © 2011 by the American Society of Neuroimaging.",,"Pedraza, S.;Puig, J.;Blasco, G.;Daunis-i-Estadella, J.;Boada, I.;Bardera, A.;Castellanos, M.;Serena, J.",2012,April,,0,
1988,Neuroimaging findings in twins discordant for Alzheimer's disease,"Data from computed tomography (CT) scans of 12 twin pairs in which one partner had Azheimer's disease (AD) and the other partner is cognitively intact were analyzed to study structural brain features associated with AD while controlling for familial factors. Visual ratings and analysis of quantified areas and volumes indicated that AD twins showed more dilation of temporal horns, lateral ventricles and third ventricle, and more atrophy of temporal robes, particularly in the anterior temporal/perisylvian area, than their healthy cotwins. Demented twins did not have smaller intracranial areas or overall brain volumes than their intact partners. The apolipoprotein ε-4 allele was associated with greater dilation of lateral ventricles and ventricular volume. Significant intrapair correlations were found for total intracranial area and volume, cerebellar area and white matter lesions.",apolipoprotein E;aged;Alzheimer disease;article;brain atrophy;brain size;brain third ventricle;clinical article;computer assisted diagnosis;diagnostic imaging;female;human;lateral brain ventricle;male;normal human;priority journal;twins;white matter,"Pedersen, N. L.;Miller, B. L.;Wetherell, J. L.;Vallø, J.;Toga, A. W.;Knutson, N.;Mehringer, C. M.;Small, G. W.;Gatz, M.",1999,,,0,
1989,"Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging","Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear.",,"Pedersen, C.;Thomsen, C.;Arlien-Søborg, P.;Praestholm, J.;Kjaer, L.;Boesen, F.;Hansen, H. S.;Nielsen, J. O.",1991,Aug,,0,
1990,Vascular cognitive impairment,"Vascular cognitive impairment encompasses a spectrum of clinically defined syndromes ranging from vascular cognitive impairment-no dementia, to vascular dementia. The underlying cerebrovascular pathology includes both overt infarction as well as rarefaction of gray and white matter. Alzheimer's pathology may coexist with vascular pathology. Diagnosis rests on identifying acquired cognitive impairment in the setting of documented cerebrovascular disease, based on clinical presentation and neuroimaging; MRI is more sensitive than CT. The course can be stepwise or gradually progressive. The clinical picture is typically dominated by deficits in executive function rather than the short-term memory deficit typical of Alzheimer's disease. No specific therapies exist, but treatment with anticholinesterase agents and N-methyl-d-aspartate antagonists may result in clinical improvement. Prevention remains paramount, with early recognition of populations at risk and early and aggressive management of risk factors, including hypertension, dyslipidemia, diabetes, and tobacco use as well as antithrombotic therapy, in appropriate populations.",,"Pedelty, L.;Nyenhuis, D. L.",2006,May,,0,
1991,"Centrum semiovale white matter CT changes associated with normal ageing, Alzheimer's disease and late life depression with and without reversible dementia","A standardized, reliable means of assessing CT attenuation numbers in the centrum semiovale and surrounding grey matter was developed. This was applied to cranial CT scans of 60 normal controls (36 aged greater than 60 years), 25 elderly patients with major depression (14 of whom had the dementia syndrome of depression), and 10 patients with Alzheimer's disease (AD). Subjects received neuropsychological evaluation. Centrum semiovale (CSO) CT attenuation numbers decreased with increasing age for both white and grey matter. White matter attenuation values best discriminated elderly controls from the three patient groups. Both white and grey matter CSO attenuation values correlated with performance on a number of cognitive tasks.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/*radiography;Brain Damage, Chronic/*radiography;Cephalometry;Cerebral Cortex/*radiography;Dementia/*radiography;Depressive Disorder/*radiography;Female;Humans;Male;Middle Aged;Reference Values;*Tomography, X-Ray Computed","Pearlson, G. D.;Rabins, P. V.;Burns, A.",1991,May,,0,
1992,What are the differences between younger and older patients with symptomatic small vessel disease?,"OBJECTIVE: Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS: Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS: In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (chi(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION: In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged </=55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.","Adult;Aged;Aged, 80 and over;Aging/pathology;Brain/pathology;Cerebral Small Vessel Diseases/complications/diagnosis/*pathology;Cognition/physiology;Cognition Disorders/etiology/pathology;Cross-Sectional Studies;Dementia, Vascular/diagnosis/psychology;Female;Humans;Image Interpretation, Computer-Assisted;Ischemic Attack, Transient/etiology/pathology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination;Neuropsychological Tests;Risk Factors;Vascular Diseases/physiopathology","Pavlovic, A. M.;Pekmezovic, T.;Zidverc-Trajkovic, J.;Jovanovic, Z.;Mijajlovic, M.;Pavlovic, D.;Tomic, G.;Sternic, N.",2011,Nov,10.1016/j.clineuro.2011.08.011,0,
1993,Baseline predictors of cognitive decline in patients with cerebral small vessel disease,"INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of cognitive impairment and vascular dementia. OBJECTIVE: We aimed to investigate predictors of cognitive decline in patients with SVD who initially presented with first-ever small subcortical stroke of lacunar type but had normal cognitive status. METHODS: A total of 294 patients with SVD were evaluated 3-5 years after initial presentation. We analyzed baseline demographic data, vascular risk factors, functional status expressed as score on modified Rankin Scale, total number of lacunar infarcts, and severity of white matter hyperintensities (WMH) on magnetic resonance imaging with Age-Related White Matter Changes scale total score (tARWMC) and Fazekas scale periventricular and deep subcortical scores. RESULTS: At follow-up, vascular cognitive impairment (VCI) on any type was detected in 188 (63.9%) of SVD patients, with 65 (22.1%) meeting criteria for vascular dementia and 123 (41.8%) presenting with cognitive impairment not dementia. Patients with VCI were older (64.4 +/- 10.3 in VCI versus 58.6 +/- 10.5 years in non-VCI; p < 0.0001) at the time of initial clinical presentation and more frequently male (57.9% VCI versus 46.2% non-VCI; p = 0.052). No difference was noted in frequency of vascular risk factors in VCI versus non-VCI cases. Multivariate logistic regression analysis adjusted by age and gender identified overall severity of WMH (tARWMC HR 1.42, 95% CI 1.01-2.00; p0.043) and total number of lacunar infarcts (HR 3.06, 95% CI 1.71-5.50, p < 0.001) as independent predictors of cognitive decline. CONCLUSION: In patients with SVD, independent predictors of VCI were baseline severity of WMH and total number of lacunar infarcts.","Adult;Aged;Aged, 80 and over;Analysis of Variance;Brain/ pathology;Brain Infarction/complications/pathology;Cerebral Small Vessel Diseases/ complications/mortality;Cognition Disorders/ diagnosis/ etiology/mortality;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Predictive Value of Tests;Retrospective Studies;Survival Analysis;White Matter/pathology","Pavlovic, A. M.;Pekmezovic, T.;Tomic, G.;Trajkovic, J. Z.;Sternic, N.",2014,,10.3233/jad-132606,0,
1994,A novel Notch3 Gly89Cys mutation in a Serbian CADASIL family,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable cause of stroke and vascular dementia in adults. We present a family from Serbia presenting with stroke and depression in the lack of vascular risk factors, with brain MRI indicating CADASIL. A novel NOTCH3 Gly89Cys mutation was located in exon 3. This report illustrates that in the setting of a positive family history with typical clinical and MRI features, even with an atypical form of pedigree, a high suspicion of CADASIL should lead to genetic testing. © 2013 Belgian Neurological Society.",adult;amnesia;arm weakness;article;CADASIL;case report;cerebrovascular accident;computer assisted tomography;depression;exon;female;gene;gene mutation;genetic screening;hemiparesis;human;human tissue;male;mild cognitive impairment;neuropsychological test;Notch3 gene;nuclear magnetic resonance imaging;paresthesia;Serbia;skin biopsy;speech disorder;transmission electron microscopy;white matter lesion,"Pavlovic, A. M.;Dobricic, V.;Semnic, R.;Lackovic, V.;Novakovic, I.;Bajcetic, M.;Sternic, N.",2013,,,0,
1995,Magnetic resonance spectroscopy in childhood AIDS encephalopathy,"Twenty-five children with acquired immunodeficiency syndrome (AIDS) underwent cranial magnetic resonance imaging and proton magnetic resonance spectroscopy. Patients were divided into 2 groups based on clinical parameters: encephalopathy and nonencephalopathy. N-acetyl aspartate/creatine ratios were compared between the 2 groups and to control data. Spectra were obtained for 2 volumes of interest: the basal ganglia region and the white matter. The mean basal ganglia region ratio for the AIDS encephalopathy patients (n = 8) was 1.12 and the ratio for the AIDS nonencephalopathy patients (n = 17) was 1.48. The ratio for the 9 controls was 1.57. The encephalopathy group had a significantly lower ratio than both the control (P < .001) and the AIDS nonencephalopathy group (P < .002). The mean white matter ratio for the encephalopathy group (n = 8) was 1.47 and for the AIDS nonencephalopathy group (n = 13) was 1.82 with a control (n = 6) ratio of 1.82. The encephalopathy patients had a lower white matter ratio than the nonencephalopathy (P < .05) patients but the ratio was not different than controls (P < .11). It is concluded that N-acetyl aspartate/creatine ratios are reduced in childhood AIDS encephalopathy and proton magnetic resonance spectroscopy may be helpful in defining brain human immunodeficiency virus-1 infection. However, further longitudinal studies are necessary to determine the sensitivity and specificity of this technique.","AIDS Dementia Complex/ diagnosis;Adolescent;Basal Ganglia/ pathology;Case-Control Studies;Child;Child, Preschool;Humans;Infant;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Protons","Pavlakis, S. G.;Lu, D.;Frank, Y.;Bakshi, S.;Pahwa, S.;Barnett, T. A.;Porricolo, M. E.;Gould, R. J.;Nozyce, M. L.;Hyman, R. A.",1995,May,,0,
1996,Diffusion-weighted magnetic resonance imaging differentiates parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy,"Progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple-system atrophy (MSA-P) may present with a similar phenotype. Magnetic resonance diffusion-weighted imaging (DWI) has been shown to be a sensitive discriminator of MSA-P from Parkinson's disease (PD). We studied 20 PSP, 11 MSA-P, 12 PD patients and 7 healthy controls in order to investigate whether regional apparent diffusion coefficients (rADCs) help distinguish PSP and MSA-P; whether rADCs are correlated with clinical disease severity scores; and the relationship between brainstem and cerebellar volumes and rADCs in PSP and MSA-P. The Unified Parkinson's Disease Rating Scale, Hoehn and Yahr score, Mini Mental State Examination, and frontal assessment battery were recorded in all patients. Regional ADCs were measured in the middle cerebellar peduncle (MCP), caudal and rostral pons, midbrain, decussating fibers of the superior cerebellar peduncle, thalamus, putamen, globus pallidus, caudate nucleus, corpus callosum, frontal and parietal white matter, as well as the centrum semiovale. In MSA-P, rADCs in the MCP and rostral pons were significantly greater than in PSP (P < 0.001 and 0.009) and PD (P < 0.001 and = 0.002). Stepwise logistic regression revealed that the MCP rADC distinguishes MSA-P from PSP with a sensitivity of 91% and a specificity of 84%. Increased brainstem rADCs were associated with motor deficit in MSA-P and PSP. Increased rADCs in the pons and MCP were associated with smaller pontine and cerebellar volumes in MSA-P. rADCs distinguish MSA-P from PSP. These have a clinical correlate and are associated with reduced brainstem and cerebellar volumes. © 2006 Movement Disorder Society.",,"Paviour, D. C.;Thornton, J. S.;Lees, A. J.;Jäger, H. R.",2007,January,,0,
1997,Striatal and white matter predictors of estimated diagnosis for Huntington disease,"Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.","Adult;*Brain/anatomy & histology/pathology;Corpus Striatum/*pathology;Cross-Sectional Studies;Female;Humans;Huntington Disease/*diagnosis/*pathology/physiopathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Models, Anatomic;Nerve Fibers, Myelinated/*pathology;Phenotype;Predictive Value of Tests","Paulsen, J. S.;Nopoulos, P. C.;Aylward, E.;Ross, C. A.;Johnson, H.;Magnotta, V. A.;Juhl, A.;Pierson, R. K.;Mills, J.;Langbehn, D.;Nance, M.",2010,May 31,10.1016/j.brainresbull.2010.04.003,0,
1998,Brain structure in preclinical Huntington's disease,"BACKGROUND: Huntington's disease (HD) is traditionally conceptualized as a degenerative disease of the striatum. Recent scientific advances, however, have suggested neurodevelopmental contributions and extrastriatal brain abnormalities. This study was designed to assess the morphology of the brain in participants who had previously undergone elective DNA analyses for the HD mutation who did not currently have a clinical diagnosis of HD (preclinical HD subjects). METHODS: Twenty-four preclinical participants with the gene expansion for HD underwent brain magnetic resonance imaging and were compared with a group of 24 healthy control subjects, matched by gender and age. RESULTS: Huntington's disease preclinical participants had substantial morphologic differences from controls throughout the cerebrum. Volume of the cerebral cortex was significantly increased in preclinical HD, whereas the basal ganglia and cerebral white matter volume were substantially decreased. CONCLUSIONS: In individuals with the HD gene mutation who are considered healthy (preclinical for manifest disease), the morphology of the brain is substantially altered compared with matched control subjects. Although decreased volumes of the striatum and cerebral white matter could represent early degenerative changes, the novel finding of enlarged cortex suggests that developmental pathology occurs in HD.",Adult;Analysis of Variance;Brain/ pathology;Demography;Female;Humans;Huntington Disease/cerebrospinal fluid/genetics/ pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mutation;Trinucleotide Repeats/genetics,"Paulsen, J. S.;Magnotta, V. A.;Mikos, A. E.;Paulson, H. L.;Penziner, E.;Andreasen, N. C.;Nopoulos, P. C.",2006,Jan 1,10.1016/j.biopsych.2005.06.003,0,
1999,Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS): study protocol for a randomised controlled trial,"BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p < 0.05, 90% power). Primary outcomes are cerebral blood flow in subcortical white matter and deep grey nuclei. Secondary outcomes are cortical grey matter cerebral blood flow and performance on cognitive tests (reaction time, information processing speed, digit span forwards and backwards, semantic fluency). DISCUSSION: Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George's University Hospitals NHS Foundation Trust. TRIAL REGISTRATION: European Union Clinical Trials Register: EudraCT number 2015-001235-20 . Registered on 13 May 2015.",Arterial spin labelling;Cerebral blood flow;Mri;Phosphodiesterase;Tadalafil;Vascular cognitive impairment;Vascular dementia,"Pauls, M. M. H.;Clarke, N.;Trippier, S.;Betteridge, S.;Howe, F. A.;Khan, U.;Kruuse, C.;Madigan, J. B.;Moynihan, B.;Pereira, A. C.;Rolfe, D.;Rostrup, E.;Haig, C. E.;Barrick, T. R.;Isaacs, J. D.;Hainsworth, A. H.",2017,May 22,,0,
2000,Clinical correlates of cognitive decline in vascular dementia,"OBJECTIVE: To determine whether demographic data, dementia severity, functional status, whole brain volume (WBV), or subcortical hyperintensity volume (SH) predict subsequent cognitive decline in vascular dementia (VaD). BACKGROUND: The identification of variables that accurately predict progressive cognitive decline in dementia has important clinical implications. METHODS: A cohort of 30 patients with VaD completed neurologic and neuropsychologic examinations and magnetic resonance imaging of the brain at baseline and again after 12 months. All participants met clinical and research criteria for VaD according to standard guidelines. Change scores were computed for measures of verbal fluency, verbal learning, and visual learning. Potential correlates of cognitive change included age, education, score on the Hachinski scale, WBV, SH, and functional ability. RESULTS: As a group, lower WBV and lower Hachinski score correlated with decline in verbal fluency and visual learning, whereas lower Hachinski score correlated with decline in verbal learning. However, when subdivided by disease type, this pattern held only for individuals with evidence of a cortical stroke at baseline. No clinical variables correlated with cognitive decline among individuals without a cortical infarction. CONCLUSIONS: Assessment of cognitive decline in VaD should be guided by dementia subtype, with particular attention directed at severity of cerebral atrophy rather than classic symptoms of infarction.","Aged;Analysis of Variance;Basal Ganglia/pathology;Body Weights and Measures;Brain/ pathology;Brain Infarction/ complications/pathology;Cerebral Cortex/pathology;Cognition Disorders/ diagnosis/etiology/pathology;Cytidine Diphosphate Choline/therapeutic use;Dementia, Vascular/ complications/drug therapy/pathology;Double-Blind Method;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Neuropsychological Tests;Nootropic Agents/therapeutic use;Predictive Value of Tests;Severity of Illness Index;Thalamus/pathology","Paul, R. H.;Cohen, R. A.;Moser, D. J.;Ott, B. R.;Sethi, M.;Sweet, L.;Browndyke, J.;Malloy, P.;Garrett, K.",2003,Mar,,0,
2001,Analysis of sub-anatomic diffusion tensor imaging indices in white matter regions of Alzheimer with MMSE score,"In this study, an attempt has been made to find the correlation between diffusion tensor imaging (DTI) indices of white matter (WM) regions and mini mental state examination (MMSE) score of Alzheimer patients. Diffusion weighted images are obtained from the ADNI database. These are preprocessed for eddy current correction and removal of non-brain tissue. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (DA) indices are computed over significant regions (Fornix left, Splenium of corpus callosum left, Splenium of corpus callosum right, bilateral genu of the corpus callosum) affected by Alzheimer disease (AD) pathology. The correlation is computed between diffusion indices of the significant regions and MMSE score using linear fit technique so as to find the relation between clinical parameters and the image features. Binary classification has been employed using support vector machine, decision stumps and simple logistic classifiers on the extracted DTI indices along with MMSE score to classify Alzheimer patients from healthy controls. It is observed that distinct values of DTI indices exist for the range of MMSE score. However, there is no strong correlation (Pearson's correlation coefficient 'r' varies from 0.0383 to -0.1924) between the MMSE score and the diffusion indices over the significant regions. Further, the performance evaluation of classifiers shows 94% accuracy using SVM in differentiating AD and control. In isolation clinical and image features can be used for prescreening and diagnosis of AD but no sub anatomic region correlation exist between these features set. The discussion on the correlation of diffusion indices of WM with MMSE score is presented in this study.",Alzheimer Disease/ pathology;Diffusion Tensor Imaging;Humans;White Matter/ pathology,"Patil, R. B.;Ramakrishnan, S.",2014,Oct,10.1016/j.cmpb.2014.06.004,0,
2002,Identification of brain white matter regions for diagnosis of Alzheimer using Diffusion Tensor Imaging,"Diffusion Tensor Imaging (DTI) technique is widely used to probe the white matter (WM) tracts, which is affected most by neurological disorders. The fractional anisotropy (FA) metric has been used predominantly to study changes in the WM tracts. Here an attempt is made to delineate specific regions of interest in the WM that may be probable indicators for the diagnosis of Alzheimer disease (AD). Genetic algorithm has been used as feature reduction method along with Adaptive Boosting (AdaBoost) machine learning technique to determine the most prominent regions in the WM that are indicators of AD. It is found in this study that Fornix region of WM is most affected by Alzheimer. Further, classification was done to differentiate between Alzheimer and Normal controls with accuracy of 84.5%. The results obtained were validated by comparing with the existing literature on Alzheimer.","Algorithms;Alzheimer Disease/ diagnosis;Anisotropy;Brain/ physiology;Brain Mapping/ methods;Diffusion Tensor Imaging;Fornix, Brain;Humans;Nerve Tissue;Reproducibility of Results;White Matter/ physiology","Patil, R. B.;Piyush, R.;Ramakrishnan, S.",2013,,10.1109/embc.2013.6611052,0,
2003,Three-dimensional imaging of the mouse neurovasculature with magnetic resonance microscopy,"Knowledge of the three-dimensional (3D) architecture of blood vessels in the brain is crucial because the progression of various neuropathologies ranging from Alzheimer's disease to brain tumors involves anomalous blood vessels. The challenges in obtaining such data from patients, in conjunction with development of mouse models of neuropathology, have made the murine brain indispensable for investigating disease induced neurovascular changes. Here we describe a novel method for ""whole brain"" 3D mapping of murine neurovasculature using magnetic resonance microscopy (muMRI). This approach preserves the vascular and white matter tract architecture, and can be combined with complementary MRI contrast mechanisms such as diffusion tensor imaging (DTI) to examine the interplay between the vasculature and white matter reorganization that often characterizes neuropathologies. Following validation with micro computed tomography (muCT) and optical microscopy, we demonstrate the utility of this method by: (i) combined 3D imaging of angiogenesis and white matter reorganization in both, invasive and non-invasive brain tumor models; (ii) characterizing the morphological heterogeneity of the vascular phenotype in the murine brain; and (iii) conducting ""multi-scale"" imaging of brain tumor angiogenesis, wherein we directly compared in vivo MRI blood volume measurements with ex vivo vasculature data.","Animals;Brain/ blood supply/pathology/radiography;Brain Neoplasms/blood supply/pathology;Disease Models, Animal;Humans;Imaging, Three-Dimensional/ methods;Magnetic Resonance Spectroscopy/ methods;Mice;Microscopy/ methods;Neoplasm Invasiveness;Neovascularization, Pathologic/pathology;Reproducibility of Results;X-Ray Microtomography","Pathak, A. P.;Kim, E.;Zhang, J.;Jones, M. V.",2011,,10.1371/journal.pone.0022643,0,
2004,White matter hyperintensities characterize monogenic frontotemporal dementia with granulin mutations,"No study but one has suggested the presence of white matter hyperintensities (WMHs) in frontotemporal dementia (FTD), limited to 4 cases carrying pathogenic Granulin (GRN) gene mutations. We investigated the presence of WMHs in a cohort of 14 FTD patients with pathogenic GRN mutations (GRN+), 28 patients without GRN mutations (GRN-) and 18 healthy controls (HC). We further considered 11 asymptomatic GRN+ subjects and 11 young age-matched healthy controls (yHC). The WMH burden was automatically computed and a voxelwise-based analysis was carried out to explore the differences in WMH brain spatial distribution. FTD-GRN+ patients had increased total WMH burden than both HC (p < 0.001) and FTD-GRN-(p = 0.01) groups. WMHs were mainly localized in the right middle frontal and superior temporal gyri, in the left superior frontal in the left parietal gyri. No significant differences of WMH burden between asymptomatic GRN+ and yHC were observed. The presence of WMHs in cases of FTD may suggest a novel mechanism of GRN disease-related neurodegeneration, may be of help in the differential diagnosis, and in guiding genetic screening.",Asymptomatic;Frontotemporal dementia;Granulin;Mri;Vbm;Wmh,"Paternico, D.;Premi, E.;Gazzina, S.;Cosseddu, M.;Alberici, A.;Archetti, S.;Cotelli, M. S.;Micheli, A.;Turla, M.;Gasparotti, R.;Padovani, A.;Borroni, B.",2016,Feb,10.1016/j.neurobiolaging.2015.11.011,0,
2005,Dyslexia susceptibility genes influence brain atrophy in frontotemporal dementia,"OBJECTIVE: In this study, we evaluated whether variations within genes specifically associated with dyslexia, namely KIAA0319, DCDC2, and CNTNAP2, were associated with greater damage of language-related regions in patients with frontotemporal dementia (FTD) and primary progressive aphasia (PPA) in particular. METHODS: A total of 118 patients with FTD, 84 with the behavioral variant of FTD (bvFTD) and 34 with PPA, underwent neuropsychological examination, genetic analyses, and brain MRI. KIAA0319 rs17243157 G/A, DCDC2 rs793842 A/G, and CNTNAP2 rs17236239 A/G genetic variations were assessed. Patients were grouped according to clinical phenotype and genotype status (GA/AA or GG). Gray matter (GM) and white matter (WM) differences were assessed by voxel-based morphometry and structural intercorrelation pattern analyses. RESULTS: Patients carrying KIAA0319 A* (GA or AA) showed greater GM and WM atrophy in the left middle and inferior temporal gyri, as compared with KIAA0319 GG (p < 0.001). The effect of KIAA0319 polymorphism was mainly reported in patients with PPA. In patients with PPA carrying at-risk polymorphism, temporal damage led to loss of interhemispheric and intrahemispheric GM and WM structural association. No effect of DCDC2 and CNTNAP2 was found. CONCLUSIONS: Genes involved in dyslexia susceptibility, such as KIAA0319, result in language network vulnerability in FTD, and in PPA in particular.",,"Paternico, D.;Premi, E.;Alberici, A.;Archetti, S.;Bonomi, E.;Gualeni, V.;Gasparotti, R.;Padovani, A.;Borroni, B.",2015,Oct,10.1212/nxg.0000000000000024,0,
2006,Neurosyphilis: A clinico- radiological study,"Purpose: Neurosyphilis is an uncommon disease. Although syphilis may promote the transmission of HIV the converse may not be true. The neuro-radiology of neurosyphilis is limited to two case series and several case reports. Our series of patients were reviewed to describe the clinical and radiological findings. Method: A retrospective chart review from 1994 to 2005 was done and demographic, clinical, laboratory and radiological findings were extracted. Patients HIV status was also recorded. Patients who satisfied the criteria for the diagnosis of neurosyphilis with the exclusion of alternate diagnoses were included. Results: Fifty-three patients were evaluated but only 41 charts were available for review. Thirty-nine of these had radiological data. The clinical spectrum included asymptomatic patients, strokes, dementia, cranial nerve palsies, spinal cord syndromes and polyradiculopathy. Imaging changes included normal findings, infarcts, meningeal based mass lesions, spinal intra-medullary hyper-intensities, cranial nerve enhancement and intra-medullary enhancing mass lesions. There was no difference in CSF cellular or chemistry findings between those with neurosyphilis who were HIV positive and those who were HIV negative. Amongst the patients where follow up was available most improved regardless of HIV status. Conclusion: Neurosyphilis has protean manifestations and can affect any central neurological system. The pathogenesis varies from inflammatory mass lesions to vascular occlusion and inflammatory damage. Syphilis should be an aetiological consideration in any neurological presentation where another cause is not obvious. The radiological features are not specific and would be seen with many inflammatory aetiologies affecting the CNS. The CSF picture is similar regardless of HIV status and patients should be managed similarly regardless of their HIV status. © 2002 African Journal of Neurological Sciences. All rights reserved.",,"Patel, V. B.;Motala, A.;Connolly, C.;Burger, I. D. P.",2008,,,0,
2007,Default mode network activity and white matter integrity in healthy middle-aged ApoE4 carriers,"Alzheimer's disease (AD) is most commonly detected during old age, but the underlying neuropathologic changes likely appear decades earlier, especially among patients possessing genetic risk factors, such as the isoform E4 of the apolipoprotein E (ApoE4). In this study, we used magnetic resonance imaging (MRI) to assess default mode network (DMN) connectivity in 22 ApoE4 non-carriers and 14 matched ApoE4 carriers as well as white matter fractional anisotropy (FA) in 15 ApoE4 non-carriers and 11 demographically matched ApoE4 carriers. Cognitive tests were also administered. All of the participants were middle-aged adults. The analysis revealed no cognitive or white matter FA differences between carriers and non-carriers. However, in DMN regions previously implicated in AD, we did detect decreased functional connectivity. Our findings suggest that functional MRI abnormalities may be detectable well before cognitive decline or white matter changes among individuals at increased genetic risk for AD.","Adult;Anxiety/genetics/psychology;Apolipoprotein E4/ genetics;Brain/ anatomy & histology;DNA/genetics;Data Interpretation, Statistical;Depression/genetics/psychology;Diffusion Tensor Imaging;Female;Genotype;Heterozygote;Humans;Image Processing, Computer-Assisted;Intelligence Tests;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Net/ physiology;Neuropsychological Tests;Principal Component Analysis;Smoking/adverse effects;Wechsler Scales","Patel, K. T.;Stevens, M. C.;Pearlson, G. D.;Winkler, A. M.;Hawkins, K. A.;Skudlarski, P.;Bauer, L. O.",2013,Mar,10.1007/s11682-012-9187-y,0,
2008,Cerebral microbleeds and cognition in patients with symptomatic small vessel disease,"BACKGROUND AND PURPOSE - : Cerebral microbleeds (CMBs) are common in cerebral small vessel disease. They may cause cognitive impairment, possibly via white matter tract disruption but previous studies have produced inconsistent results. We determined whether CMB number and location are associated with impaired cognition in symptomatic small vessel disease and whether any association was independent of other magnetic resonance imaging markers of small vessel disease. METHODS - : One hundred sixteen patients with lacunar stroke and radiological leukoaraiosis were studied. Neuropsychological assessment was performed. CMBs on gradient echo images were assessed using the Brain Observer Microbleed Rating Scale criteria. Magnetic resonance imaging measures, including diffusion tensor imaging, were also analyzed. Associations between cognitive function and the presence, number, and location of CMBs were determined. RESULTS - : CMBs were present in 46 (39.7%) patients. CMB number correlated weakly with executive function (r=0.22; P=0.022) but not with other cognitive indices. CMBs count in the top decile (≥9 CMB, N=12) was more strongly associated with poor executive function; this association remained significant after controlling for T2-lesion load, brain volume, lacune count, and mean diffusivity (b=-0.51; P=0.043). CONCLUSIONS - : In symptomatic small vessel disease, CMB number was weakly associated with executive dysfunction. There seemed to be a threshold effect with the association being largely accounted for by an association of impaired executive function with high CMB count. No association of CMBs with other cognitive domains, including processing speed, was found. © 2013 American Heart Association, Inc.",,"Patel, B.;Lawrence, A. J.;Chung, A. W.;Rich, P.;MacKinnon, A. D.;Morris, R. G.;Barrick, T. R.;Markus, H. S.",2013,February,,0,
2009,Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral microvascular disease: study in elderly patients with dementia,"BACKGROUND AND PURPOSE: Virchow-Robin spaces (VRSs) are CSF spaces that accompany blood vessels as they perforate the brain substance. Dilatation of VRS is associated with microangiopathy. Microvascular disease has a major etiologic and pathogenetic role in dementias. To our knowledge, no investigators have looked at the relationship between dilated VRS on MR imaging and cerebral microvascular disease. The aim of our study was to test the hypothesis that dilatation of VRS is associated with subcortical vascular dementia. METHODS: We recruited 75 patients with Alzheimer's disease (n = 35), ischemic vascular dementia (n = 24), or frontotemporal dementia (n = 16) and 35 healthy volunteers. We assessed deep white matter and periventricular hyperintensities and the severity of VRS dilatation, as scored on MR images. Statistical group comparisons and multiple regression analyses were performed to quantify the relationship between imaging features and diagnoses. RESULTS: White matter lesions were more common in patients with ischemic vascular dementia than in those with Alzheimer's disease or healthy volunteers (P < .01). VRS scores were significantly higher in patients with vascular dementia than in patients with AD (P < .001), patients with FTD (P < .01), or healthy volunteers (P < .001). VRS scores accounted for 29% of the variance in the regression model, and scores for periventricular hyperintensity accounted for 2%. CONCLUSION: VRS dilatation is common in diseases associated with microvascular abnormality and can be used as a diagnostic tool to differentiate vascular dementias from degenerative dementias.","Aged;Cerebral Ventricles/ pathology;Cerebrovascular Disorders/complications/ pathology;Dementia/complications/ pathology;Dilatation, Pathologic;Female;Humans;Male;Middle Aged","Patankar, T. F.;Mitra, D.;Varma, A.;Snowden, J.;Neary, D.;Jackson, A.",2005,Jun-Jul,,0,
2010,Virchow-Robin space dilatation may predict resistance to antidepressant monotherapy in elderly patients with depression,"BACKGROUND: Late-life depressive disorders have been linked to cerebrovascular disease (the vascular depression hypothesis). Treatment resistance may be associated with vascular-based lesions in the white matter and basal ganglia. Virchow-Robin spaces (VRS) are cerebrospinal fluid spaces associated with microangiopathy of small cerebral vessels. This study tested the hypothesis that dilation of Virchow-Robin spaces seen on Magnetic Resonance Imaging (MRI) is associated with treatment resistance in elderly depressed individuals. METHODS: 50 patients with late-onset (age over 60 years) major depressive disorder (29 responders to monotherapy, 21 non-responders to monotherapy) and 35 normal volunteers were recruited. Assessment of deep white matter lesions [WML] and periventricular hyperintensities [PVH] (both with the Scheltens rating scale score, [Scheltens, P., Barkhof, F., Leys, D., et al. (1993) A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging. J Neurol Sci;114(1):7-12.]) and the severity of VRS dilatation (using a new scale) were scored from MRI images. Statistical group comparisons and multiple regression analyses were performed to quantify the relationship between imaging features and clinical outcome. RESULTS: There was a trend for greater WML Scheltens scores in the monotherapy resistant group compared to responders and control subjects, but only using the basal ganglia VRS score was there a statistically significant difference. A score of 2 or greater on the VRS score was 80% sensitive and 62% specific in predicting non-response to antidepressant monotherapy. The VRS score accounted for 38% of the variance in the multiple regression model and the PVH score, which was an independent predictor of outcome, contributed another 6%. LIMITATIONS: Numbers are small and type II errors possible, especially for the Scheltens ratings. Treatment response was limited to response or non-response to monotherapy and was retrospectively derived. The VRS scale was originally designed for use in patients with vascular dementia and has not been used before in affective disorders. Although all depressed subjects were late-onset, it is possible that depression led to vascular disease rather than vice versa. CONCLUSION: VRS dilatation is common in diseases associated with microvascular abnormality, which is the presumed basis of vascular depression in the elderly. VRS score may be useful in determining which patients are less likely to respond to antidepressant monotherapy. Prospective studies of patients with a wider range of treatment responses are indicated.","Aged;Aged, 80 and over;Antidepressive Agents/ therapeutic use;Basal Ganglia Cerebrovascular Disease/diagnosis/drug therapy/psychology;Cerebral Ventricles/pathology;Cerebrospinal Fluid;Cerebrovascular Disorders/diagnosis/ drug therapy/psychology;Dementia, Vascular/diagnosis/ drug therapy/psychology;Depressive Disorder, Major/diagnosis/ drug therapy/psychology;Dilatation, Pathologic;Drug Resistance;Drug Therapy, Combination;Electroconvulsive Therapy;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Treatment Failure","Patankar, T. F.;Baldwin, R.;Mitra, D.;Jeffries, S.;Sutcliffe, C.;Burns, A.;Jackson, A.",2007,Jan,10.1016/j.jad.2006.06.024,0,
2011,Familial presenile dementia with bitemporal atrophy,"This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer's disease.","Alzheimer Disease/diagnosis/*genetics/*pathology/psychology;Atrophy;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/etiology;Middle Aged;Neuropsychological Tests;Pedigree;Temporal Lobe/*pathology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon","Passant, U.;Ostojic, J.;Froelich Fabre, S.;Gustafson, L.;Lannfelt, L.;Larsson, E. M.;Nilsson, K.;Rosen, I.;Elfgren, C.",2004,,10.1159/000077156,0,
2012,The Problematic Issue of Kufs Disease Diagnosis as Performed on Rectal Biopsies: A Case Report,"Kufs disease, the late-onset form of a group of neurodegenerative disorders, known as the neuronal ceroid-lipofuscinoses, is characterized by intraneuronal/extraneuronal accumulation of proteins that are visible as fingerprint inclusions and granular osmiophilic deposits (GRODs) at the ultrastructural level. A problematic case of Kufs disease in a 53-year-old female affected by progressive gait disturbances, myoclonus, epilepsy, and profound dementia is presented. Laboratory, biochemical, and molecular genetic tests were unremarkable. A magnetic resonance imaging of the brain revealed a moderate atrophy over both hemispheres with no white matter changes. Ultrastructural examination of rectal mucosa biopsies showed fingerprint inclusions in perivascular smooth muscle cells. Pathological examination of autoptic tissues showed numerous intraneuronal PAS-positive, diastase-resistant inclusions corresponding to GRODs at the ultrastructural examination, but no fingerprint inclusions. Cerebellum, skeletal, and cardiac muscles, skin, and liver were unaffected. The present case illustrates the diagnostic difficulties encountered while examining Kufs disease pathological samples. Main problematic issues include (1) specificity and diagnostic value of fingerprint inclusions when found exclusively in perivascular smooth muscle cells; (2) safe distinction of GRODs from lipofuscin inclusions in cerebral tissue; and (3) reliability in using extraneural tissues and, in particular, rectal mucosa biopsies for diagnostic purposes.",,"Pasquinelli, G.;Cenacchi, G.;Le Piane, E.;Russo, C.;Aguglia, U.",2004,January/February,,0,
2013,Two phase 2 multiple ascending-dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-to-moderate Alzheimer's disease,"Vanutide cridificar (ACC-001), an immunotherapeutic vaccine, is a potentially disease-modifying therapy that aims to reduce brain amyloid-beta (Abeta) plaques in patients with Alzheimer's disease (AD). ACC-001 was evaluated in two phase 2a, multicenter, randomized, third party-unblinded, placebo-controlled, multiple ascending-dose studies of ACC-001 (3mug, 10mug, 30mug) with and without QS-21 adjuvant that enrolled patients with mild-to-moderate AD (n=245). Patients were treated with up to five doses of study vaccine or placebo and followed for safety and tolerability (primary objective) and anti-Abeta IgG immunogenicity (secondary objective) up to 12 months after the last vaccination. Exploratory assessments included cognitive/functional measures, brain magnetic resonance imaging (MRI) volumetry, and pharmacodynamic markers in plasma and cerebrospinal fluid (CSF). The most frequent treatment-emergent adverse events (>10) were local injection reactions and headache. Amyloid-related imaging abnormalities with vasogenic edema occurred in two (0.8) patients (ACC-001 30mug QS-21; ACC-001 10mug). ACC-001 QS-21 elicited consistently higher peak and sustained anti-Abeta IgG titers compared with ACC-001 alone. Plasma Abetax-40 was significantly higher in all ACC-001 QS-21 groups versus placebo (weeks 16-56), with no evidence of dose response. Exploratory cognitive evaluations, volumetric brain MRI, and CSF biomarkers did not show differences or trends between treatment groups and placebo. ACC-001 with or without QS-21 adjuvant has an acceptable safety profile in patients with mild-to-moderate AD.",adult;aged;Alzheimer disease/dt [Drug Therapy];antibody titer;article;brain edema;cerebrospinal fluid;cognition;cohort analysis;controlled study;depression/si [Side Effect];diarrhea/si [Side Effect];disease severity;drug efficacy;drug safety;drug tolerability;female;follow up;headache/si [Side Effect];heart arrest/si [Side Effect];heart infarction/si [Side Effect];human;immunogenicity;injection site erythema/si [Side Effect];injection site pain/si [Side Effect];injection site swelling/si [Side Effect];lung cancer/si [Side Effect];major clinical study;male;nuclear magnetic resonance imaging;outcome assessment;pharmacodynamics;phase 2 clinical trial;priority journal;randomized controlled trial;treatment response;vaccination;vasculitis/si [Side Effect];volumetry;immunoglobulin G1/ec [Endogenous Compound];placebo;qs 21/ae [Adverse Drug Reaction];qs 21/cb [Drug Combination];qs 21/dt [Drug Therapy];qs 21/ct [Clinical Trial];vanutide cridificar/ae [Adverse Drug Reaction];vanutide cridificar/cb [Drug Combination];vanutide cridificar/dt [Drug Therapy];vanutide cridificar/ct [Clinical Trial],"Pasquier, F.;Sadowsky, C.;Holstein, A.;Leterme, G. L. P.;Peng, Y.;Jackson, N.;Fox, N. C.;Ketter, N.;Liu, E.;Ryan, J. M.",2016,,10.3233/JAD-150376,0,
2014,Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts,"Cerebral atrophy (CA) in stroke patients is associated with poststroke dementia and may reflect underlying neurodegenerative pathology. Therefore, regional CA may be valuable to study in patients who develop poststroke dementia. The aim of this study was to test the reproducibility of a qualitative rating scale of CA on MRI. MRI scans were performed in 50 consecutive patients (age range 19-81) admitted for an acute hemispheric ischemic stroke. CA was assessed on 2 occasions 24 h apart, on axial T2-weighted sequences by 4 independent observers. We evaluated CA in 13 regions on a 0-3 scale. The sum of the subscores was called the CA score (range: 0-39). The level of agreement was expressed by kappa statistics as well as by analysis of variance for interexaminer reproducibility studies. The mean CA scores ranged from 2.8 to 11.0, indicating the low prevalence of CA in this sample. Complete agreement was reached in 41.7% during the first assessment and in 44.1% in the second assessment. The interobserver agreement was moderate in the first session (mean overall kappa: 0.48) and substantial in the second (mean overall kappa: 0.67). The intraobserver agreement was good for all raters (mean kappa: 0.65). Standardized to the range of the scale, standard deviations of the differences between CA scores of the 4 raters in the 2 sessions were 11.1 and 11.2%; within raters it was 4.4%. We conclude that the assessment of CA using this rating scale is possible in stroke patients. It provides regional atrophy measurements and is reproducible when performed by 1 rater.","Adult;Aged;Aged, 80 and over;Atrophy;Brain/*pathology;Cerebral Infarction/*diagnosis;Evaluation Studies as Topic;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Observer Variation;Reproducibility of Results","Pasquier, F.;Leys, D.;Weerts, J. G.;Mounier-Vehier, F.;Barkhof, F.;Scheltens, P.",1996,,,0,
2015,"Dementia, apathy, and thalamic infarcts","Two men in their seventies were referred for dementia that had been evolving for more than 18 months. Neither had obvious signs of focal neurological deficits and both had normal computed tomographic (CT) scans. Their mini-mental state examination (MMSE) scores were 14 and 21, respectively. Memory disorders, apraxia, agnosia, and, in one case, language impairment were present, Because of an apathetic state and a history of hypertension, in addition to right facial paresis for emotional expression in the first patient and a small-step gait and frequent urination in the second, magnetic resonance imaging (MRI) was performed, The imaging revealed bilateral paramedian thalamic artery infarcts. Further family interviews revealed a vigilance disorder at the onset of the cognitive disturbances that had not been mentioned earlier because it was thought to be related, in the first patient, to emotional stress (friend's death) and, in the second, to severe infectious bronchitis. These observations illustrate the difficulty of diagnosing some cases of strategic infarct dementia, especially when acute onset is not clear because of the lack of focal motor or sensory deficits. They point out the potential diagnostic power of apathy, which is rare in the first stage of Alzheimer's disease, and suggest subcortical or vascular dementia. The relationship between apathy, loss of psychic self-activation, and the 'athymhormia syndrome' is discussed.",,"Pasquier, F.;Lebert, F.;Petit, H.",1995,1995,,0,
2016,Relevance of white matter changes to pre- and poststroke dementia,"White matter changes are often associated with stroke, risk factors for stroke, and dementia. From a theoretical point of view, they may be associated with an increased risk of pre- or poststroke dementia because (i) they are linked with subtle cognitive decline, which may add to the consequences of the stroke lesions and of associated Alzheimer pathology; and (ii) they indicate an increased risk of stroke recurrence. The aim of this study was to evaluate the contribution of white matter changes to pre- and poststroke dementia. The relationship between preexisting dementia and white matter changes was evaluated in the Lille stroke-dementia cohort. We assessed the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke, by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. White matter changes were rated on CT with the Blennow's rating scale. Thirty-three of 202 patients were demented before stroke (16.3%; 95% confidence interval: 11.2-21.4); the logistic regression analysis found that female sex, family dementia, white matter changes, and cerebral atrophy were independently associated with prestroke dementia. White matter changes were also associated with an increased risk of poststroke dementia, 2 years after stroke onset. Thus, white matter changes contribute to dementia occurring in stroke patients.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/epidemiology;Brain/*pathology;Brain Ischemia/*pathology/psychology;Cerebral Hemorrhage/*pathology/psychology;*Cognition;Cohort Studies;Dementia/complications/*epidemiology/pathology;Female;Humans;Male;Middle Aged;Recurrence;Risk Factors;Stroke/complications/*pathology/psychology","Pasquier, F.;Henon, H.;Leys, D.",2000,Apr,,0,
2017,Transcranial Doppler of the middle cerebral artery indicates regional gray matter cerebral perfusion,"OBJECTIVE: We determined if transcranial color-coded Doppler derived hemodynamics are associated with MRI-based cerebral blood flow (CBF) in regions clinically important to dementia in healthy middle-aged adults. APPROACH: In 30 subjects (18m/12f; age = 52 +/- 1 years), blood flow velocity (BFV) and cerebrovascular conductance (CVC) were measured with transcranial color-coded Doppler (TCCD) at the middle cerebral artery (MCA) and cerebral blood flow (CBF) was assessed with arterial spin labeled perfusion MRI. MAIN RESULTS: BFV and CVC were associated with hippocampus (r = 0.58 and r = 0.61, both p < 0.01) and occipitoparietal (r = 0.50 and r = 0.58, both p < 0.01) CBF. CVC was further associated with posterior cingulate CBF (r = 0.58 p < 0.01). Independent of age and sex, BFV and CVC were associated with hippocampus (r = 0.59 and r = 0.55, both p < 0.003) and occipitoparietal (r = 0.50 and r = 0.57, both p < 0.01) CBF. CVC was independently associated with posterior cingulate CBF (r = 0.38, p = 0.049). SIGNIFICANCE: TCCD-measured BFV and CVC of the MCA are indicators of cerebral perfusion to clinically valuable brain regions in healthy middle-aged adults. TCCD may not be a good indicator of blood flow to cerebral white matter.",,"Pasha, E. P.;Tarumi, T.;Haley, A. P.;Tanaka, H.",2017,Nov 30,,0,
2018,Association of Aortic Stiffness with Cognition and Brain Aging in Young and Middle-Aged Adults: The Framingham Third Generation Cohort Study,"Aortic stiffness is associated with cognitive decline and cerebrovascular disease late in life, although these associations have not been examined in young adults. Understanding the effects of aortic stiffness on the brain at a young age is important both from a pathophysiological and public health perspective. The aim of this study was to examine the cross-sectional associations of aortic stiffness with cognitive function and brain aging in the Framingham Heart Study Third Generation cohort (47% men; mean age, 46 years). Participants completed the assessment of aortic stiffness (carotid-femoral pulse wave velocity), a neuropsychological test battery assessing multiple domains of cognitive performance and magnetic resonance imaging to examine subclinical markers of brain injury. In adjusted regression models, higher aortic stiffness was associated with poorer processing speed and executive function (Trail Making B-A; β±SE, -0.08±0.03; P<0.01), larger lateral ventricular volumes (β±SE, 0.09±0.03; P<0.01) and a greater burden of white-matter hyperintensities (β±SE, 0.09±0.03; P<0.001). When stratifying by age, aortic stiffness was associated with lateral ventricular volume in young adults (30-45 years), whereas aortic stiffness was associated with white-matter injury and cognition in midlife (45-65 years). In conclusion, aortic stiffness was associated with cognitive function and markers of subclinical brain injury in young to middle-aged adults. Prospective studies are needed to examine whether aortic stiffening in young adulthood is associated with vascular cognitive impairment later in life.",,"Pase, M. P.;Himali, J. J.;Mitchell, G. F.;Beiser, A.;Maillard, P.;Tsao, C.;Larson, M. G.;Decarli, C.;Vasan, R. S.;Seshadri, S.",2016,1,,0,
2019,Interarm differences in systolic blood pressure and the risk of dementia and subclinical brain injury,"INTRODUCTION: This study examined whether interarm differences in systolic blood pressure (IDSBP) >/=10 mm Hg were associated with the risk of incident dementia and subclinical brain injury. METHODS: Between 1992 and 1998, 2063 participants of the Framingham Heart Study underwent assessment of IDSBP with results related to the 10-year risk of incident dementia including clinically characterized Alzheimer's disease. Secondary outcomes included markers of subclinical brain injury on magnetic resonance imaging. RESULTS: High IDSBP were associated with a greater risk of incident dementia (hazard ratio [HR] 1.92; 95% confidence interval [CI], 1.09-3.40) and Alzheimer's disease (HR, 2.32; 95% CI, 1.29-4.18), but only in those who carried an apolipoprotein E (APOE) epsilon4 allele. IDSBP also predicted lower total brain volumes and more prevalent silent brain infarcts in those who were APOE epsilon4 positive. DISCUSSION: High IDSBP were associated with an increased risk of dementia, including clinical Alzheimer's disease, and subclinical brain injury in those who were APOE epsilon4 positive.",,"Pase, M. P.;Beiser, A.;Aparicio, H.;DeCarli, C.;Vasan, R. S.;Murabito, J.;Seshadri, S.",2016,Apr,10.1016/j.jalz.2015.09.006,0,
2020,Atypical clinicoradiological course in a case panancephalic variant of Creutzfeldt-Jakob disease,"Introduction. Creutzfeldt-Jakob disease (CJD) is the most frequent of the human transmissible spongiform encephalopathies. Pathogenic mechanisms of CJD are still unknown. Sporadic CJD, the most habitual, is clinically characterized by rapidly progressive dementia, myoclonia and ataxia. Panencephalic variant CJD, typically from Japan, is characterized by extensive involvement of the cerebral white and gray matter. International interest has grown from more than one decade ago in relation to the diagnosis of new variant (vCJD). New protocols of MR imaging have contributed to the early diagnosis of CJD with specific signs. Case report. We report a case of panencephalic CJD, with atypical clinical presentation and unusual MR imaging findings. Discussion. Our patient developed visual and psychiatric symptoms. Brain MR imaging showed extensive white matter lesions in posterior parietal lobe and occipital regions, which disappeared after steroid treatment. The most characteristic radiological sign for sporadic CJD is the high signal intensity of the basal ganglia, for vCJD the pulvinar sign and, for panencephalic CJD the presence of periventricular white matter lesions, with tendency to the spread when the disease progress. In serial MR imaging studies of our patient, we could see how typical signs were appearing. However, the complete and unusual resolution of the original white matter lesions makes us to think about a possible inflammatory component, in some time in the evolution of white matter damage.",,"Pascual Lozano, A. M.;Salvador Aliaga, A.;Coret Ferrer, F.;Láinez Andrés, J. M.",2006,October,,0,
2021,Atypical clinicoradiological course in a case panancephalic variant of Creutzfeldt-Jakob,"INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is the most frequent of the human transmissible spongiform encephalopathies. Pathogenic mechanisms of CJD are still unknown. Sporadic CJD, the most habitual, is clinically characterized by rapidly progressive dementia, myoclonia and ataxia. Panencephalic variant CJD, typically from Japan, is characterized by extensive involvement of the cerebral white and gray matter. International interest has grown from more than one decade ago in relation to the diagnosis of new variant (vCJD). New protocols of MR imaging have contributed to the early diagnosis of CJD with specific signs. CASE REPORT: We report a case of panencephalic CJD, with atypical clinical presentation and unusual MR imaging findings. DISCUSSION: Our patient developed visual and psychiatric symptoms. Brain MR imaging showed extensive white matter lesions in posterior parietal lobe and occipital regions, which disappeared after steroid treatment. The most characteristic radiological sign for sporadic CJD is the high signal intensity of the basal ganglia, for vCJD the pulvinar sign and, for panencephalic CJD the presence of periventricular white matter lesions, with tendency to the spread when the disease progress. In serial MR imaging studies of our patient, we could see how typical signs were appearing. However, the complete and unusual resolution of the original white matter lesions makes us to think about a possible inflammatory component, in some time in the evolution of white matter damage.",adult;article;case report;Creutzfeldt Jakob disease;fatality;female;human;nuclear magnetic resonance imaging;pathology;pathophysiology,"Pascual Lozano, A.;Salvador-Aliaga, A.;Coret, F.;Lainez-Andres, J.",2006,,,0,
2022,Brain glucose metabolism in vascular white matter disease with dementia: differentiation from Alzheimer disease,"BACKGROUND AND PURPOSE: The boundary between vascular dementia and Alzheimer disease (AD) continues to be unclear. Some posit that gradually progressive vascular dementia, as with small vessel disease, is simply vascular disease plus AD. Because AD presents a characteristic pattern on fluorodeoxyglucose positron emission tomography, we sought to determine whether the fluorodeoxyglucose pattern of vascular dementia resembled more AD or the pattern in nondemented patients with severe microvascular brain disease. METHODS: Vascular disease patients were selected on the basis of confluent white matter lesions on both hemispheres. Among them, with a similar degree of vascular disease on MRI, neuropsychological testing separated groups with dementia and without dementia. Patients with AD and healthy controls were also studied. The 4 groups, with 12 subjects each, were matched by age, gender, and educational level. Fluorodeoxyglucose distribution was analyzed using both voxel-based and volume of interest methods. RESULTS: The AD group had the characteristic pattern of bilaterally decreased metabolism in parieto-temporal association cortex and precuneus. By contrast, patients with vascular disease and dementia had a similar anatomic pattern to that of the vascular patients without dementia, but with greater metabolic abnormalities, particularly in the frontal lobes and deep nuclei. CONCLUSIONS: The anatomy of metabolic abnormalities in vascular disease with dementia suggests that, at least in some cases, dementia with vascular disease may be independent of AD. The metabolic abnormality involves the thalamus, caudate, and frontal lobe, a pattern concordant with the neuropsychological findings of impaired executive function characteristic of vascular dementia.","Aged;Alzheimer Disease/*metabolism/pathology/psychology;Brain/pathology/radionuclide imaging;Brain Chemistry/*physiology;Dementia, Vascular/*metabolism/pathology/psychology;Female;Fluorodeoxyglucose F18;Glucose/*metabolism;Humans;Image Interpretation, Computer-Assisted;Leukoencephalopathies/*metabolism/pathology/psychology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Positron-Emission Tomography;Radiopharmaceuticals","Pascual, B.;Prieto, E.;Arbizu, J.;Marti-Climent, J.;Olier, J.;Masdeu, J. C.",2010,Dec,10.1161/strokeaha.110.591552,0,
2023,Triglycerides are negatively correlated with cognitive function in nondemented aging adults,"OBJECTIVE: Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI). DESIGN/METHOD: Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62-94) years and a mean education of 15.6 (SD = 2.9; range: 8-23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning. RESULTS: Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function. CONCLUSION: Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function. (PsycINFO Database Record",,"Parthasarathy, V.;Frazier, D. T.;Bettcher, B. M.;Jastrzab, L.;Chao, L.;Reed, B.;Mungas, D.;Weiner, M.;DeCarli, C.;Chui, H.;Kramer, J. H.",2017,Sep,,0,
2024,Memory binding and white matter integrity in familial Alzheimer's disease,"Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease.","Adult;Aged;Alzheimer Disease/ pathology/ physiopathology;Brain Mapping;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Image Processing, Computer-Assisted/methods;Male;Memory/ physiology;Memory Disorders/physiopathology;Middle Aged;Mutation/genetics;Neuropsychological Tests;White Matter/ pathology","Parra, M. A.;Saarimaki, H.;Bastin, M. E.;Londono, A. C.;Pettit, L.;Lopera, F.;Della Sala, S.;Abrahams, S.",2015,May,10.1093/brain/awv048,0,
2025,Extensive intracranial involvement with multiple dissections in a case of giant cell arteritis,"A 56-year-old man presented with weight loss, articular pain and minor neurological symptoms progressing over 1 month. Neurosonological evaluation suggested occlusion in intracranial segments of the left vertebral artery (VA) and of both internal carotid arteries (ICA) and hypoechoic halo sign in both superficial temporal arteries. The diagnosis of giant cell arteritis was supported by inflammatory markers and confirmed by biopsy. Despite early steroid initiation, he manifested fluctuant vascular deficits and became lethargic. Brain MRI indicated watershed infarcts and intracranial dissections of left VA and both ICA. The patient was stabilised with the association of prednisolone 2 mg/kg, methotrexate and oral anticoagulation. Since then he has been neurologically asymptomatic and control imaging showed only residual intracranial left VA stenosis, with no signs of temporal artery inflammation or new vascular lesions. This is to the best of our knowledge, the first reported clinical case with such an extensive intracranial involvement with multiple dissections. Copyright 2014 BMJ Publishing Group. All rights reserved.",C reactive protein;methotrexate;prednisolone;steroid;warfarin;adult;anorexia;apathy;aphasia;article;aseptic necrosis;asymptomatic disease;atherosclerosis;blood vessel biopsy;case report;cerebrospinal fluid analysis;computer assisted tomography;echography;facial nerve paralysis;follow up;gait disorder;giant cell arteritis;headache;hemiparesis;hip arthroplasty;hip prosthesis;human;internal carotid artery occlusion;laboratory test;male;mental deterioration;middle aged;nausea;normochromic normocytic anemia;nuclear magnetic resonance imaging;pain;pleocytosis;priority journal;psychomotor disorder;quadriplegia;sleep disorder;steroid therapy;thrombocytosis;treatment outcome;vertebral artery stenosis;vomiting;body weight loss,"Parra, J.;Domingues, J.;Sargento-Freitas, J.;Santana, I.",2014,,10.1136/bcr-2014-204130,0,2026
2026,Extensive intracranial involvement with multiple dissections in a case of giant cell arteritis,"A 56-year-old man presented with weight loss, articular pain and minor neurological symptoms progressing over 1 month. Neurosonological evaluation suggested occlusion in intracranial segments of the left vertebral artery (VA) and of both internal carotid arteries (ICA) and hypoechoic halo sign in both superficial temporal arteries. The diagnosis of giant cell arteritis was supported by inflammatory markers and confirmed by biopsy. Despite early steroid initiation, he manifested fluctuant vascular deficits and became lethargic. Brain MRI indicated watershed infarcts and intracranial dissections of left VA and both ICA. The patient was stabilised with the association of prednisolone 2 mg/kg, methotrexate and oral anticoagulation. Since then he has been neurologically asymptomatic and control imaging showed only residual intracranial left VA stenosis, with no signs of temporal artery inflammation or new vascular lesions. This is to the best of our knowledge, the first reported clinical case with such an extensive intracranial involvement with multiple dissections. Copyright 2014 BMJ Publishing Group. All rights reserved.",,"Parra, J.;Domingues, J.;Sargento-Freitas, J.;Santana, I.",2014,,,0,
2027,Is multi-infarct dementia representative of vascular dementias? A retrospective study,"Multi-infarct dementia (MID) indicates a dementia disorder primarily caused by multiple cerebral infarcts. Since other pathogenetic mechanisms cause vascular dementia we evaluated clinical, CT scan and CSF neurochemical parameters of 134 MID and 67 PVD (probable vascular dementia) patients. We found no differences with regard to the presence of major risk factors. Only TIA/stroke episodes and focal neurological signs were significantly more frequent in MID than in PVD cases, an anticipable result on the basis of MID definition. CT scan findings showed a prevalence of subcortical with respect to cortical lesions in both groups, with a higher frequency in MID patients. Subjects with deep infarcts more frequently showed TIA/stroke episodes and diabetes mellitus. No differences were detectable in CSF monoamine metabolite levels. We conclude that in the majority of vascular dementias subcortical damage seems to have a major pathogenetic role.",adult;aged;article;cerebrospinal fluid;computer analysis;computer assisted tomography;female;human;male;multiinfarct dementia;priority journal;cerebrovascular accident;transient ischemic attack,"Parnetti, L.;Mecocci, P.;Santucci, C.;Gaiti, A.;Petrini, A.;Longo, A.;Cadini, D.;Caputo, N.;Signorini, E.;Senin, U.",1990,,,0,
2028,"Electrocortical mapping, MRI, and neuropsychological measures: Evidence of Alzheimer's disease in the presence of vascular lesions","We report here a case study of a 76-year-old woman with a high school education, whose presenting psychiatric symptomatology indicated dementia of unknown etiology. Neuropsychological test results were consistent with AD, but diagnosis was complicated by an MRI showing a large right hemisphere cortical infarct and scattered subcortical changes leading to a diagnosis of possible AD. Electrocortical mapping showed the right hemisphere infarct, and gave independent evidence suggestive of AD in the relatively intact left hemisphere. This case demonstrates the utility of multidimensional assessment as an aid to differential diagnosis.",aged;Alzheimer disease;article;brain infarction;brain mapping;case report;female;human;multiinfarct dementia;neuropsychology;nuclear magnetic resonance,"Parks, R. W.;Zec, R. F.;Kuhn, M.;Vicari, S.;Feldman, E.;Coburn, K. L.;Wesson Ashford, J.;Crockett, D. J.;Moreno, M. A.;Rashid, A.",1991,,,0,
2029,Executive function mediates effects of white matter hyperintensities on episodic memory,"This study examined the relationship between white matter hyperintensities (WMH) and executive functioning on episodic memory in a group of older adults who were cognitively normal or diagnosed with MCI or dementia. Volumetric magnetic resonance imaging (MRI) measures of total brain volume, white matter hyperintensity volume, and hippocampal volume along with age, education, and gender were evaluated as predictors of episodic memory. WMH were found to influence both episodic memory and executive functioning independently of other variables. The influence WMH on episodic memory was mediated by executive functioning and was completely eliminated when the interaction between executive functioning and hippocampal volume was entered in the regression model. The results indicate that executive functioning mediates the effects of WMH on episodic memory but that executive functioning and hippocampal volume can also interact such that executive functioning can exacerbate or ameliorate the influence of hippocampal volume on episodic memory. © 2011 Elsevier Ltd.",,"Parks, C. M.;Iosif, A. M.;Farias, S.;Reed, B.;Mungas, D.;DeCarli, C.",2011,August,,0,
2030,Analysis of Cerebral Blood Flow with Single Photon Emission Computed Tomography in Mild Subcortical Ischemic Vascular Dementia,"PURPOSE: The mechanism of cognitive dysfunction of subcortical ischemic vascular dementia (SIVaD) is not yet fully understood. The objective of this study was to investigate and compare the distribution of regional cerebral perfusion (CP) change in the mild forms of SIVaD, a relatively homogeneous subtype of vascular dementia, using statistical parametric mapping (SPM) analysis of the technetium-99m hexamethylproplyeneamineoxime (Tc-99m HMPAO) single photon emission computed tomography (SPECT). MATERIALS AND METHODS: A total of 28 patients with mild SIVaD and 33 healthy controls were prospectively recruited and underwent SPECT imaging studies between January 2012 and May 2013. SPECT was performed to measure the regional CP, and SPM was applied to the analysis of the SPECT data. RESULTS: The regional CP was significantly decreased in the bilateral insula, anterior and posterior cingulated gyrus, precentral gyrus, and subcallosal gyrus as well as the right inferior parietal lobule in the SIVaD patients compared to the controls (corrected p = 0.01). The pattern of CP abnormality correlated well with those previously reported in later forms of SIVaD. CONCLUSIONS: Reduction of CP in the brain areas mentioned was present earlier on in the natural course of SIVaD pathophysiology. Our study suggests that cognitive dysfunction of SIVaD may be related to these regional CP deficits.",,"Park, S. Y.;Yoon, H.;Lee, N.;Oh, J. K.;Yoo Ie, R.;Kim, S. H.;Chung, Y. A.",2014,Dec,10.1007/s13139-014-0287-z,0,
2031,"A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with stroke","Objective: To examine the synergistic effects of both computer-assisted cognitive rehabilitation (CACR) and transcranial direct current stimulation (tDCS) on cognitive function in patients with stroke. Methods: The current double-blind, sham-controlled study enrolled a total of 11 patients who were newly diagnosed with stroke. The patients of the tDCS group (n=6) completed sessions of the Korean computer-assisted cognitive rehabilitation program five times a week for 30 minutes a session during a mean period of 18.5 days concomitantly with the anodal tDCS over the bilateral prefrontal cortex combined with the CACR. The patients of the control group (n=5) also completed sessions of the sham stimulation during a mean period of 17.8 days. Anodal tDCS over bilateral prefrontal cortex (F3 and F4 in 10-20 EEG system) was delivered for 30 minutes at an intensity of 2 mA. Cathode electrodes were applied to the non-dominant arm. All the patients were evaluated using the Seoul Computerized Neuropsychological Test (SCNT) and the Korean Mini-Mental State Examination. Results: Mann-Whitney U test revealed a significant difference between the two groups. The patients of the tDCS group achieved a significant improvement in the post/pre ratio of auditory continuous performance test and visual continuous performance test on the SCNT items. Conclusion: Our results indicate that the concomitant use of the tDCS with CACR to the prefrontal cortex may provide additional beneficial effects in improving the cognitive dysfunction for patients with stroke. 2014 The Korean Neurosurgical Society.",aged;article;auditory continuous performance test;brain hemorrhage;brain infarction;brain vasospasm;cerebrovascular accident rh [Rehabilitation];clinical article;cognition;cognitive defect;cognitive rehabilitation;computer assisted therapy;computer assisted tomography;controlled study;double blind procedure;female;hearing test;human;male;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;pilot study;prefrontal cortex;psychologic test;randomized controlled trial;rank sum test;seoul computerized neuropsychological test;Stroop test;subarachnoid hemorrhage;transcranial direct current stimulation;vision test;visual continuous performance test,"Park, S. H.;Koh, E. J.;Choi, H. Y.;Ko, M. H.",2013,,,0,
2032,"Decreased hemoglobin levels, cerebral small-vessel disease, and cortical atrophy: among cognitively normal elderly women and men","BACKGROUND: Decreased hemoglobin levels increase the risk of developing dementia among the elderly. However, the underlying mechanisms that link decreased hemoglobin levels to incident dementia still remain unclear, possibly due to the fact that few studies have reported on the relationship between low hemoglobin levels and neuroimaging markers. We, therefore, investigated the relationships between decreased hemoglobin levels, cerebral small-vessel disease (CSVD), and cortical atrophy in cognitively healthy women and men. METHODS: Cognitively normal women (n = 1,022) and men (n = 1,018) who underwent medical check-ups and magnetic resonance imaging (MRI) were enrolled at a health promotion center. We measured hemoglobin levels, white matter hyperintensities (WMH) scales, lacunes, and microbleeds. Cortical thickness was automatically measured using surface based methods. Multivariate regression analyses were performed after controlling for possible confounders. RESULTS: Decreased hemoglobin levels were not associated with the presence of WMH, lacunes, or microbleeds in women and men. Among women, decreased hemoglobin levels were associated with decreased cortical thickness in the frontal (Estimates, 95% confidence interval, -0.007, (-0.013, -0.001)), temporal (-0.010, (-0.018, -0.002)), parietal (-0.009, (-0.015, -0.003)), and occipital regions (-0.011, (-0.019, -0.003)). Among men, however, no associations were observed between hemoglobin levels and cortical thickness. CONCLUSION: Our findings suggested that decreased hemoglobin levels affected cortical atrophy, but not increased CSVD, among women, although the association is modest. Given the paucity of modifiable risk factors for age-related cognitive decline, our results have important public health implications.",,"Park, S. E.;Kim, H.;Lee, J.;Lee, N. K.;Hwang, J. W.;Yang, J. J.;Ye, B. S.;Cho, H.;Kim, H. J.;Kim, Y. J.;Jung, N. Y.;Son, T. O.;Cho, E. B.;Jang, H.;Jang, E. Y.;Hong, C. H.;Lee, J. M.;Kang, M.;Shin, H. Y.;Na, D. L.;Seo, S. W.",2016,Jan,10.1017/s1041610215000733,0,
2033,SPECT myocardial perfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary small vessel disease. Although the symptoms are exclusively neurological, arteriopathy is generalized. We performed cardiac evaluation using myocardial perfusion single photon emission computed tomography (SPECT), dual-source 128-channel multidetector computed tomography (MDCT) angiogram, echocardiogram, and electrocardiogram (ECG) in a 46-year-old woman with CADASIL. No abnormal findings were observed on MDCT angiogram, echocardiogram, or ECG. However, SPECT demonstrated reversible perfusion defects in the left anterior descending artery territory. We suggest that myocardial perfusion SPECT is a valuable tool to identify risk from cardiovascular accident in CADASIL patients. Copyright © 2013 Lippincott Williams & Wilkins.",adult;article;CADASIL;cardiac imaging;case report;computed tomographic angiography;echocardiography;electrocardiogram;evaluation study;female;heart muscle perfusion;human;left anterior descending coronary artery;multidetector computed tomography;single photon emission computer tomography,"Park, S. A.;Cho, K. H.;Kim, N. H.;Yang, C. Y.;Park, S. H.",2013,,,0,
2034,Case report: Bipolar disorder as the first manifestation of CADASIL,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease, clinically characterized by variable manifestations of migraine, recurrent transient ischemic attack or lacunar strokes, cognitive decline, and mood disturbances. However, manic episodes have rarely been documented as an initial symptom of CADASIL and bipolar disorder presenting as the first manifestation in CADASIL has not been reported previously from evaluations by psychiatrists or psychological testing by psychologists.Case presentation: A 53 year old woman developed symptoms of mania in her 50s leading to a personality change involving a continuously labile mood and irritability over a number of years. Neuropsychological testing revealed an intact memory, but impairment in attention and executive function. In the Rorschach test, she showed a high level of cognitive rigidity. Magnetic resonance imaging findings were very consistent with a diagnosis of CADASIL, which was confirmed by genetic testing for NOTCH3 mutations. Atypical antipsychotics proved to be helpful in treating her manic symptoms and for behavior control.Conclusion: We present a novel case of CADASIL that first presented as bipolar disorder. We contend that when patients show a late onset personality change or chronically irritable mood that deteriorates over many years, an organic cause such as CADASIL must be considered. Further studies are needed to better understand the exact impacts of cerebral tissue lesions and psychiatric symptoms in CADASIL patients. © 2014 Park et al.; licensee BioMed Central Ltd.",,"Park, S.;Park, B.;Koh, M. K.;Joo, Y. H.",2014,,,0,
2035,Lesions in the splenium of the corpus callosum: Clinical and radiological implications,"Background: Brain MRI may unexpectedly display abnormalities in splenium of the corpus callosum (SCC). However, the clinical implications of this lesion are unclear and are not always consistent with ischemic infarctions. We performed this study to clarify the clinical and radiological implications in patients with SCC lesions. Methods: We retrospectively reviewed consecutive patients with MRI- reported SCC changes between 2009 and 2012. We analyzed clinical and radiological findings, etiologies, cognitive impairment, and clinical outcomes. Results: We found 30 patients (16 females; mean 50.5 years) who had SCC lesions on MRI. Confusion was the most common clinical finding in 50% of cases. Cerebral infarction was the most common etiology (50%). The most consistent SCC changes on MRI were low signal in T1WI, high signal on T2WI and FLAIR, and high signal on DWI. We classified SCC lesions into in situ SCC lesions (SCC only) and multiple (SCC plus) lesions for patients with multiple lesions. The clinical symptoms of SCC only lesions were relatively mild. Cognitive functions were evaluated by Mini Mental State Examination (MMSE) and clinical dementia rating (CDR) scale at the time of discharge and patients with SCC only lesions showed less impaired cognition compared with those with SCC plus lesions. Clinical outcomes were evaluated by the modified Rankin scale at 1 month and patients with SCC only lesions revealed good clinical outcomes compared with those with SCC plus lesions. Conclusions: MRI-reported SCC lesions may have heterogeneous etiologies and present with various symptoms. The clinical course and outcome are relatively good, particularly in small isolated and oval shaped SCC lesions.",adult;aged;article;brain damage;brain infarction;child;clinical article;Clinical Dementia Rating;clinical evaluation;clinical feature;cognitive defect;confusion;corpus callosum;female;human;male;Mini Mental State Examination;nuclear magnetic resonance imaging;outcome assessment;prognosis;Rankin scale;retrospective study,"Park, M. K.;Hwang, S. H.;Jung, S.;Hong, S. S.;Kwon, S. B.",2014,,,0,
2036,Vascular risk factors and the effect of white matter lesions on extrapyramidal signs in Alzheimer's disease,"Background: Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD. Methods: We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML). Results: EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61-2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84-2.41), pvWML (OR 2.09-3.14), and dWML (OR 1.83-3.42). Conclusions: EPSs in AD are associated with selected vascular risk factors as well as WMLs. Copyright © International Psychogeriatric Association 2010.",age;aged;Alzheimer disease;article;body posture;brain damage;cognitive defect;controlled study;diabetes mellitus;extrapyramidal symptom;female;gait disorder;gender;human;major clinical study;male;nuclear magnetic resonance imaging;risk factor;tremor;white matter,"Park, M. H.;Min, J. Y.;Kwon, D. Y.;Lee, S. H.;Na, H. R.;Cho, S. T.;Na, D. L.",2011,,,0,
2037,Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment,"Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment. © 2014 Elsevier Inc.",,"Park, J. H.;Seo, S. W.;Kim, C.;Kim, S. H.;Kim, G. H.;Kim, S. T.;Jeon, S.;Lee, J. M.;Oh, S. J.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Shin, J. S.;Kim, C. H.;Noh, Y.;Cho, H.;Yoon, C. W.;Kim, H. J.;Ye, B. S.;Ewers, M.;Weiner, M. W.;Lee, J. H.;Werring, D. J.;Na, D. L.",2014,January,,0,
2038,Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment,"OBJECTIVE: Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. METHODS: We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. RESULTS: Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, ""pure"" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). INTERPRETATION: Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/radionuclide imaging;Amyloid/ metabolism;Aniline Compounds;Cerebral Amyloid Angiopathy;Cerebral Hemorrhage/ etiology/ radionuclide imaging;Cognition Disorders/ etiology/radionuclide imaging;Female;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography;Stroke, Lacunar/pathology/radionuclide imaging;Thiazoles","Park, J. H.;Seo, S. W.;Kim, C.;Kim, G. H.;Noh, H. J.;Kim, S. T.;Kwak, K. C.;Yoon, U.;Lee, J. M.;Lee, J. W.;Shin, J. S.;Kim, C. H.;Noh, Y.;Cho, H.;Kim, H. J.;Yoon, C. W.;Oh, S. J.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Lee, J. H.;Ewers, M.;Weiner, M. W.;Werring, D. J.;Na, D. L.",2013,May,10.1002/ana.23845,0,
2039,CADASIL as a Useful Medical Model and Genetic Form of Vascular Depression,"Objective The main magnetic resonance imaging (MRI) findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are white matter hyperintensities (WMHs), lacunar infarctions, and cerebral microbleeds (CMBs). The purpose of this study was to investigate the effects of these three neuroimaging markers of CADASIL on depression to determine whether CADASIL is a useful medical model supporting the vascular depression hypothesis. Methods Eighty-four subjects with CADASIL, aged 34–86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. The effects of WMH, lacunar infarctions, and CMBs were analyzed by path analyses and multivariate logistic regression analyses. Results Patients with CADASIL exhibited frequencies of 17.9% for major depressive disorder (MDD) and 10.7% for minor depressive disorder. The frequency of MDD increased from 5.0% to 46.2% as WMH volume increased from first quartile to fourth quartile. WMH volume (OR: 1.03, 95% CI: 1.003–1.06) in patients with CADASIL was associated with the current depressive disorder. Path analyses demonstrated that only WMH volume was associated with the Korean version of the short form Geriatric Depression Scale score, Center for Epidemiologic Studies Depression Scale score, and 17-item Hamilton depression scale score. The effects of lacunar infarctions and CMBs on depression were not significant in path analyses and multivariate logistic regression analyses. Conclusions This study demonstrates that WMHs are closely associated with depression in patients with CADASIL. This supports that CADASIL might be a useful medical model and genetic form of vascular depression.",Notch3 receptor;adult;aged;article;brain hemorrhage;brain size;CADASIL;Center for Epidemiological Studies Depression Scale;clinical evaluation;disease association;female;genotype;Geriatric Depression Scale;Hamilton Depression Rating Scale;human;image analysis;lacunar stroke;major clinical study;major depression;male;middle aged;mini international neuropsychiatric interview;neuroimaging;nuclear magnetic resonance imaging;therapy effect;vascular depression;white matter hyperintensity;white matter lesion,"Park, J. H.;Jeon, B. H.;Lee, J. S.;Newhouse, P. A.;Taylor, W. D.;Boyd, B. D.;Kim, K. W.;Kim, M. D.",2017,,10.1016/j.jagp.2017.03.013,0,
2040,Small deep white matter lesions are associated with right-to-left shunts in migraineurs,"The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 +/- 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) >/= 11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.","Adolescent;Adult;Female;Humans;Intracranial Embolism/complications/ pathology;Male;Migraine Disorders/diagnosis/etiology/ pathology;Nerve Fibers, Myelinated/ pathology;Prospective Studies;Registries;Retrospective Studies;Tension-Type Headache/diagnosis/etiology/pathology;Young Adult","Park, H. K.;Lee, S. Y.;Kim, S. E.;Yun, C. H.;Kim, S. H.",2011,Mar,10.1007/s00415-010-5771-5,0,
2041,Subcortical whiter matter hyperintensities within the cholinergic pathways of patients with dementia and parkinsonism,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease (AD) and Parkinson disease dementia (PDD). This study aimed to evaluate the relationship between loss of white matter cholinergic pathways and cognitive function in patients with AD, diffuse Lewy body disease (DLB), and PDD. METHODS: The subjects included 20 patients with AD, 17 with DLB, 21 with PDD, and 20 healthy controls. The extent of WMHs within cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) and was compared among the different diseases. RESULTS: The mean CHIPS scores were similar among the three dementia groups (AD vs. DLB vs. PDD = 34.6 +/- 17.9 vs. 32.4 +/- 14.1 vs. 31.8 +/- 14.5, p = 0.781 by ANCOVA) and higher than those of controls (11.5 +/- 7.6, p = 0.001 by ANCOVA). CONCLUSIONS: Losses of cholinergic pathways were similar among AD, DLB, and PDD groups, and more severe cognitive dysfunction was associated with elevated WMHs. These findings suggest that interruption of acetylcholine pathways may be related to cognitive dysfunction in these three diseases, even though they have different pathological mechanisms.","Aged;Aged, 80 and over;Analysis of Variance;Cholinergic Agents/ metabolism;Dementia/ pathology;Female;Humans;Imaging, Three-Dimensional;Lewy Body Disease/pathology;Magnetic Resonance Imaging;Male;Neural Pathways/ metabolism/pathology;Neuropsychological Tests;Parkinsonian Disorders/ pathology;White Matter/ metabolism/ pathology","Park, H. E.;Park, I. S.;Oh, Y. S.;Yang, D. W.;Lee, K. S.;Choi, H. S.;Ahn, K. J.;Kim, J. S.",2015,,10.1016/j.jns.2015.03.046,0,
2042,Prevalence and risk factors of cerebral white matter changes and silent infarcts on brain computed tomography scans among community-dwelling healthy adults: The PRESENT project,"Cerebral white matter changes (WMCs) and silent brain infarcts (SBIs) are common radiologic findings in neurologically asymptomatic elderly people, but are associated with an increased risk of subsequent stroke. We investigated the prevalence and risk factors for these cerebral changes on brain computed tomography (CT) in 480 community-dwelling healthy Korean adults without stroke or dementia, who were recruited for an early health program. Cerebral WMCs were defined as the presence of approximately 5 mm wide ill-defined and moderately hypodense lesions, and SBIs were defined as the presence of >2 mm wide well-defined hypodense lesions. Of the 480 patients, 49 (10.2%) had cerebral WMCs and SBIs findings on brain CT. The prevalence of WMCs and SBIs increased with age: the prevalence was 2.4%, 9%, and 32% for subjects in their 50, 60s, and 70s, respectively. In addition, hypertension, abdominal obesity, increased levels of homocysteine and high sensitivity C-reactive protein were significantly associated with cerebral WMCs and SBIs. Our study suggests that regular monitoring of risk factors is required to prevent cerebral WMCs and SBIs and decrease the incidence of stroke and dementia in healthy individuals.",C reactive protein;D dimer;fibrinogen;high density lipoprotein cholesterol;homocysteine;low density lipoprotein cholesterol;triacylglycerol;abdominal obesity;age;aged;article;cerebral white matter changes;cholesterol blood level;community care;computed tomography scanner;computer assisted tomography;controlled study;erythrocyte sedimentation rate;female;human;human experiment;hypertension;image analysis;incidence;Korean (people);male;neuroimaging;normal human;prevalence;protein blood level;radiological parameters;risk factor;silent brain infarct;triacylglycerol blood level;Phillips Brilliance CT 6 slice,"Park, H.;Jo, J.;Cheong, J. S.;Chang, H.;Lee, H. S.;Lee, S. H.;Suk, S. H.",2014,,,0,
2043,Modeling the interactions of Alzheimer-related genes from the whole brain microarray data and diffusion tensor images of human brain,"In recent years the genome-wide microarray-based gene expression profiles and diffusion tensor images (DTI) in human brain have been made available with accompanying anatomic and histology data. The challenge is to integrate various types of data to investigate the interactions of genes that are associated with specific neurological disorder. In this study, we analyzed the whole brain microarray data and the physical connectivity of the hippocampus with other brain regions to identify the genes related to Alzheimer's disease and their interactions with proteins. We generated a physical connectivity map of the left and right hippocampuses with 12 other brain regions and identified 33 Alzheimer-related genes that interact with many proteins. These genes are highly linked to the development of Alzheimer's disease. In Alzheimer's brain both brain regions and inter-regional communications through the white matter are often hampered. So far the connectivity of regions in Alzheimer's brain has been studied mostly at the functional level using functional MRI (fMRI). Analyzing the inter-regional fiber connectivity without tracking crossing-fiber regions often provides coarse and inaccurate results. A few deep brain fibers were analyzed but the inter-regional fiber connectivity was not analyzed in their studies. The inter-regional fiber connectivity analysis can provide comprehensive and measurable degradation of fiber tracts in AD patients' brains, but is not easy to perform. We tracked crossing-fiber regions and identified genes with high expression levels in the fiber pathways of the hippocampus. The interactions of the genes with other proteins can provide comprehensive and measurable degradation of fiber tracts in Alzheimer brains. To the best of our knowledge, this is the first attempt to integrate the whole brain microarray data with DTI data to identify specific genes and their interactions.",,"Park, B.;Lee, W.;Han, K.",2012,2012,,0,
2044,Homocysteine and Real-Space Navigation Performance among Non-Demented Older Adults,"BACKGROUND: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. OBJECTIVE: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. METHODS: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. RESULTS: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (beta= 0.31; p = 0.003 and beta= 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. CONCLUSION: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults.",Apoe;Alzheimer's disease;homocysteine;mild cognitive impairment;spatial navigation;subjective cognitive decline;vascular factors,"Parizkova, M.;Andel, R.;Lerch, O.;Markova, H.;Gazova, I.;Vyhnalek, M.;Hort, J.;Laczo, J.",2017,,,0,
2045,Early visual function impairment in CADASIL,"The authors carried out genetic analyses and visual electrophysiologic evaluations in six asymptomatic sons and daughters of patients with symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Three subjects showed Notch3 Cys146Tyr missense mutation and a dysfunction of the outer, middle, and innermost retinal layers, with normal neural conduction in postretinal visual pathways, whereas in the remaining subjects without genetic mutations, no electrophysiologic abnormalities were found. An early vascular retinal impairment in CADASIL may precede the onset of clinical manifestations.","Adolescent;Adult;Brain/pathology;Child;Dementia, Multi-Infarct/complications/genetics/*physiopathology;Electroretinography;Evoked Potentials, Visual;Female;Humans;Magnetic Resonance Imaging;Male;Neural Conduction;Oscillometry;Proto-Oncogene Proteins/deficiency/genetics;*Receptors, Cell Surface;Receptors, Notch;Retina/*physiopathology;Vision Disorders/*etiology/physiopathology","Parisi, V.;Pierelli, F.;Fattapposta, F.;Bianco, F.;Parisi, L.;Restuccia, R.;Malandrini, A.;Ferrari, M.;Carrera, P.",2003,Jun 24,,0,
2046,Potential role of diffusion tensor MRI in the differential diagnosis of mild cognitive impairment and Alzheimer's disease,"OBJECTIVE: The purpose of this study was to evaluate the fractional anisotropy values of several white matter tracts with the aim of differentiating a healthy population from persons with mild cognitive impairment or Alzheimer's disease. SUBJECTS AND METHODS: Seventy-nine patients with memory impairment and 16 volunteer controls participated in the study. MRI was performed with a 1.5-T system. Conventional MR images and diffusion tensor images were obtained for all participants. The diffusion tensor imaging data were postprocessed, and low b-value, fractional anisotropy, and fractional anisotropy color-coded maps were calculated. With the three maps as an anatomic reference, fractional anisotropy was measured for hippocampal formations, superior longitudinal fascicles, posterior cingulate gyri, and the splenium of the corpus callosum. Kruskal-Wallis and Steel-type multiple-comparison nonparametric tests were performed for the statistical analysis. RESULTS: The fractional anisotropy values for the splenium of the corpus callosum, bilateral posterior cingulate gyri, and bilateral superior longitudinal fascicles of patients with mild cognitive impairment and those with probable Alzheimer's disease were significantly lower than the values of controls. No differences were found in hippocampal formations in any group. No significant difference was found in fractional anisotropy values in comparisons of mild cognitive impairment versus possible Alzheimer's disease and probable Alzheimer's disease or comparisons of probable Alzheimer's disease and possible Alzheimer's disease. CONCLUSION: Diffusion tensor imaging is a promising technique for the evaluation of patients with probable mild cognitive impairment. Early detection of the disease expands the treatment options, increasing the likelihood of a good clinical response and enhancing the quality of life of patients and their relatives. Further studies with larger populations are needed to confirm the role of diffusion tensor imaging in the evaluation of memory impairment.","Alzheimer Disease [pathology] [psychology];Anisotropy;Cognition Disorders [diagnosis] [etiology];Corpus Callosum [pathology];Diagnosis, Differential;Diffusion Magnetic Resonance Imaging;Gyrus Cinguli [pathology];Hippocampus [pathology];Prospective Studies;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Parente, D. B.;Gasparetto, E. L.;Cruz, L. C.;Domingues, R. C.;Baptista, A. C.;Carvalho, A. C.",2008,,10.2214/ajr.07.2617,0,
2047,Ultra-high resolution in-vivo 7.0T structural imaging of the human hippocampus reveals the endfolial pathway,"The hippocampus is a very important structure in memory formation and retrieval, as well as in various neurological disorders such as Alzheimer's disease, epilepsy and depression. It is composed of many intricate subregions making it difficult to study the anatomical changes that take place during disease. The hippocampal hilus may have a unique neuroanatomy in humans compared to that in monkeys and rodents, with field CA3h greatly enlarged in humans compared to that in rodents, and a white-matter pathway, called the endfolial pathway, possibly only present in humans. In this study we have used newly developed 7.0T whole brain imaging sequence, balanced steady-state free precession (bSSFP) that can achieve 0.4mm isotropic images to study, in vivo, the anatomy of the hippocampal hilus. A detailed hippocampal subregional segmentation was performed according to anatomic atlases segmenting the following regions: CA4, CA3, CA2, CA1, SRLM (stratum radiatum lacunosum moleculare), alveus, fornix, and subiculum along with its molecular layer. We also segmented a hypointense structure centrally within the hilus that resembled the endfolial pathway. To validate that this hypointense signal represented the endfolial pathway, we acquired 0.1mm isotropic 8-phase cycle bSSFP on an excised specimen, and then sectioned and stained the specimen for myelin using an anti-myelin basic protein antibody (SMI 94). A structure tensor analysis was calculated on the myelin-stained section to show directionality of the underlying fibers. The endfolial pathway was consistently visualized within the hippocampal body in vivo in all subjects. It is a central pathway in the hippocampus, with unknown relevance in neurodegenerative disorders, but now that it can be visualized noninvasively, we can study its function and alterations in neurodegeneration.","CA1 Region, Hippocampal/anatomy & histology;CA2 Region, Hippocampal/anatomy & histology;CA3 Region, Hippocampal/anatomy & histology;Hippocampus/ anatomy & histology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Neural Pathways/ anatomy & histology;Whole Body Imaging","Parekh, M. B.;Rutt, B. K.;Purcell, R.;Chen, Y.;Zeineh, M. M.",2015,May 15,10.1016/j.neuroimage.2015.02.029,0,
2048,Relationship of grey and white matter abnormalities with distance from the surface of the brain in multiple sclerosis,"Objective To assess the association between proximity to the inner (ventricular and aqueductal) and outer ( pial) surfaces of the brain and the distribution of normal appearing white matter (NAWM) and grey matter (GM) abnormalities, and white matter (WM) lesions, in multiple sclerosis (MS). Methods 67 people with relapse-onset MS and 30 healthy controls were included in the study. Volumetric T1 images and high-resolution (1 mm3) magnetisation transfer ratio (MTR) images were acquired and segmented into 12 bands between the inner and outer surfaces of the brain. The first and last bands were discarded to limit partial volume effects with cerebrospinal fluid. MTR values were computed for all bands in supratentorial NAWM, cerebellar NAWM and brainstem NA tissue, and deep and cortical GM. Band WM lesion volumes were also measured. Results Proximity to the ventricular surfaces was associated with progressively lower MTR values in the MS group but not in controls in supratentorial and cerebellar NAWM, brainstem NA and in deep and cortical GM. The density of WM lesions was associated with proximity to the ventricles only in the supratentorial compartment, and no link was found with distance from the pial surfaces. Conclusions In MS, MTR abnormalities in NAWM and GM are related to distance from the inner and outer surfaces of the brain, and this suggests that there is a common factor underlying their spatial distribution. A similar pattern was not found for WM lesions, raising the possibility that different factors promote their formation.",brain cortex;brain stem;cerebrospinal fluid;clinical article;congenital malformation;gray matter;human;multiple sclerosis;pia mater;white matter lesion,"Pardini, M.;Sudre, C. H.;Prados, F.;Yaldizli, ö;Sethi, V.;Muhlert, N.;Samson, R. S.;van de Pavert, S. H.;Cardoso, M. J.;Ourselin, S.;Gandini Wheeler-Kingshott, C. A. M.;Miller, D. H.;Chard, D. T.",2016,,,0,
2049,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoancepahlopathy presenting with postpartum psychosis and late-onset stroke,"Aim: To describe the unusual presentation of a novel family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoancepahlopathy. Presentation of cases: The clinical features of five patients from three successive generations are described. The index patient presented with postpartum psychosis followed by cognitive decline. Brain imaging revealed no temporal pole involvement. Genetic testing was performed by full scan of the entire NOTCH3 gene revealing the R169C mutation. Multiple cardiovascular risk factors and late-onset strokes were present in the family. Conclusion: The combination of atypical psychiatric onset, absence of anterior temporal lesions, presence of cardiovascular risk factors and late-onset stroke may obscure the correct diagnosis for many years and requires a high index of suspicion.",arginine;cysteine;dipeptidyl carboxypeptidase inhibitor;Notch3 receptor;adult;aged;article;brain radiography;CADASIL;cardiovascular risk;cerebrovascular accident;clinical article;clinical feature;cognitive defect;family study;female;gene mutation;genetic screening;human;hypertension;late onset disorder;middle aged;NOTCH3 gene;nuclear magnetic resonance imaging;priority journal;puerperal psychosis;rare disease;risk assessment;temporal lobe;very elderly,"Paraskevas, G. P.;Constantinides, V. C.;Bougea, A.;Gerakoulis, E.;Yapijakis, C.;Kararizou, E.;Kapaki, E.",2016,,,0,
2050,CADASIL and autoimmunity: Coexistence in a family with the R169C mutation at exon 4 of the NOTCH3 gene,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by mutations of the NOTCH3 gene, which result in degeneration of vascular smooth muscle cells, arteriolar stenosis, and impaired cerebral blood flow. For clinicians this is the commonest hereditary adult-onset condition causing stroke and vascular dementia at middle age. Atypical phenotypes have been recognized, and the disease is probably underdiagnosed in the wider stroke population. Coexistence of autoimmunity is atypical and has been described only in occasional patients. Methods: Three members of a Greek family from the island of Lesvos of North East Greece were evaluated. The patients come from a four-generation family in which there were at least seven members with clinical data suggestive of CADASIL. We describe here the clinical, imaging and biochemical findings in this family with R169C mutation at exon 4 and presenting additional clinical and biochemical findings suggestive of autoimmune disorder. DNA was extracted from whole blood using standard procedures for sequencing. Results: Three affected members of this family carried the R169C. In a phenotypic analysis of affected individuals from four generations with CADASIL, the disease was characterized by migraine attacks, recurrent subcortical infarcts, and cognitive decline with typical anterior temporal lobe white matter lesions. At least 3 mutation carriers from two generations had increased antinuclear antibody (ANA) titers and various combinations of rash, joint pains, photosensitivity, and renal involvement. Conclusion: This is a rare description of the coexistence of autoimmunity in CADASIL patients with possible worsening clinical effects. The study extends the spectrum of atypical presentation of CADASIL. The coexistence of autoimmunity does not necessarily exclude CADASIL, but may cause an additional diagnostic and therapeutic challenge. This autoimmune disorder may have increased the severity of the disease and, additionally, may be related to the pathogenetic mechanisms of CADASIL. It is possible that the NOTCH3 mutation alone is not enough to trigger autoimmunity since, in the case of our family, the R169C mutation has already been described in other families with no evidence of coexistent autoimmunity. Other genetic or environmental factors or interactions and/or common pathways between the vascular and immune systems are probably co-operating. Further, prospective studies are needed to clarify the prevalence and types of autoimmune disorders present in CADASIL families.",,"Paraskevas, G. P.;Bougea, A.;Synetou, M.;Vassilopoulou, S.;Anagnostou, E.;Voumvourakis, K.;Iliopoulos, A.;Spengos, K.",2014,22,,0,
2051,A cortical form of CADASIL with cerebral Aβ amyloidosis,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was diagnosed by genetic testing in a 53-year-old patient, 10 years before death. Following two strokes with partial recovery, he developed rapidly progressive cognitive decline 3 years before death. Neuropathology confirmed CADASIL. Characteristic arteriolar changes were associated with subcortical infarcts, and status cribrosus in basal ganglia and the cortico-subcortical junctions. Leukoencephalopathy was very mild. Severe arteriolar changes in the cerebral cortex and leptomeninges were associated with numerous intracortical microinfarcts. There was abundant Abeta deposition throughout the cerebral cortex, mainly as Aβ42 diffuse plaques, frequently periarteriolar. There was no cerebral amyloid angiopathy apart from rare Aβ40 deposits around Notch3-positive deposits. Amyloid plaques were rare. Tau pathology was minimal. Alzheimer disease associated with CADASIL has been described, but the few reported cases had abundant amyloid plaques, amyloid angiopathy, fibrillar plaques and neurofibrillary tangles. Aβ accumulation could result from abnormal Aβ synthesis or impaired elimination due to the arteriolar changes of CADASIL. We did not find Aβ deposits in our other CADASIL cases with milder cortical arteriolar changes. Additional genetic predisposing factors were not identified. This case suggests that besides the classical, purely subcortical form of CADASIL, a ""cortical"" form with numerous lacunar infarcts and Aβ deposition in the cerebral cortex may occur and may be difficult to differentiate clinically from Alzheimer disease. © Springer-Verlag 2010.",amyloid beta protein;amyloid beta protein[1-42];Notch3 receptor;tau protein;adult;Alzheimer disease;amyloid plaque;anamnesis;article;ataxia;autopsy;basal ganglion;brain cortex;CADASIL;case report;cerebrovascular accident;clinical feature;cognitive defect;depression;disease association;disease course;dysarthria;family history;fatality;fluency disorder;gene mutation;genetic analysis;genetic predisposition;hemiparesis;human;human tissue;image analysis;leptomeninx;male;memory disorder;mental deterioration;migraine with aura;neurofibrillary tangle;neuroimaging;neuropathology;neuropsychological test;nuclear magnetic resonance imaging;pons;priority journal;protein synthesis;vascular amyloidosis;white matter,"Paquet, C.;Jouvent, E.;Mine, M.;Vital, A.;Hugon, J.;Chabriat, H.;Gray, F.",2010,,,0,
2052,Marchiafava-Bignami disease with dementia: Severe cerebral metabolic depression revealed by PET,"The Cerebral Metabolic Rate of Glucose (CMRGlu) was measured with positron emission tomography and 18F-FDG in a patient with Marchiafava-Bignami Disease (MBD)-related dementia. Despite MRI evidence of lesions essentially limited to the corpus callosum (CC), but consistent with the cognitive pattern of cortical dementia, the CMRGlu was markedly reduced in the frontal and temporo-parieto-occipital association cortices. Disruption of cortico-cortical networks crossing the CC presumably contributed to, but may not in and by itself explain, the severity of the clinical-metabolic findings in this patient. An additional role could be played by microscopic white matter lesions and/or neocortical neuronal loss, which have been occasionnally observed in post-mortem studies of MBD patients.",adult;article;brain injury;brain metabolism;case report;clinical trial;cognition;corpus callosum;dementia;glucose utilization;human;male;nuclear magnetic resonance imaging;positron emission tomography;priority journal,"Pappata, S.;Chabriat, H.;Levasseur, M.;Legault-Demare, F.;Baron, J. C.",1994,,,0,
2053,Processing speed in normal aging: effects of white matter hyperintensities and hippocampal volume loss,"Changes in cognitive functioning are said to be part of normal aging. Quantitative MRI has made it possible to measure structural brain changes during aging which may underlie these decrements which include slowed information processing and memory loss. Much has been written on white matter hyperintensities (WMH), which are associated with cognitive deficits on tasks requiring processing speed and executive functioning, and hippocampal volume loss, which is associated with memory decline. Here we examine volumetric MRI measures of WMH and hippocampal volume loss together in relation to neuropsychological tests considered to be measures of executive functioning and processing speed in 81 non-demented elderly individuals, aged 75-90. Correlational analysis showed that when controlling for age, both greater WMH volume and smaller hippocampal volume were correlated with slower performances on most tests with the exception of a battery of continuous performance tests in which only WMH was correlated with slower reaction time (RT). We then performed a series of hierarchical multiple regression analyses to examine the independent contributions of greater WMH volume and reduced hippocampal volume to executive functioning and processing speed. The results showed that for the four measures requiring executive functioning and speed of processing, WMH volume and hippocampal volume combined predicted between 21.4% and 37% of the explained variance. These results suggest that WM integrity and hippocampal volume influence cognitive decline independently on tasks involving processing speed and executive function independent of age.","Aged;Aged, 80 and over;Aging/pathology/*physiology;Brain/pathology/*physiopathology;Executive Function/*physiology;Female;Hippocampus/pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests/*statistics & numerical data;Psychomotor Performance/*physiology","Papp, K. V.;Kaplan, R. F.;Springate, B.;Moscufo, N.;Wakefield, D. B.;Guttmann, C. R.;Wolfson, L.",2014,,10.1080/13825585.2013.795513,0,
2054,Susac syndrome,"Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by an ills investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified: ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.",,"Papo, T.;Biousse, V.;Lehoang, P.;Fardeau, C.;N'Guyen, N.;Le Thi Huong, D.;Aumaitre, O.;Bousser, M. G.;Godeau, P.;Piette, J. C.",1998,January,,0,
2055,Cognition and gray and white matter characteristics of presymptomatic C9orf72 repeat expansion,"OBJECTIVE: To investigate cognitive function, gray matter volume, and white matter integrity in the presymptomatic stage of chromosome 9 open reading frame 72 repeat expansion (C9orf72RE). METHODS: Presymptomatic C9orf72RE carriers (n = 18) and first-degree family members without a pathogenic expansion (healthy controls [HC], n = 15) underwent a standardized protocol of neuropsychological tests, T1-weighted MRI, and diffusion tensor imaging within our cohort study of autosomal dominant frontotemporal dementia (FTD). We investigated group differences in cognitive function, gray matter volume through voxel-based morphometry, and white matter integrity by means of tract-based spatial statistics. We correlated cognitive change with underlying gray or white matter. RESULTS: Our data demonstrate lower scores on letter fluency, Stroop card I, and Stroop card III, accompanied by white matter integrity loss in tracts connecting the frontal lobe, the thalamic radiation, and tracts associated with motor functioning in presymptomatic C9orf72RE compared with HC. In a subgroup of C9orf72RE carriers above 40 years of age, we found gray matter volume loss in the thalamus, cerebellum, and parietal and temporal cortex. We found no significant relationship between subtle cognitive decline and underlying gray or white matter. CONCLUSIONS: This study demonstrates that a decline in cognitive functioning, white matter integrity, and gray matter volumes are present in presymptomatic C9orf72RE carriers. These findings suggest that neuropsychological assessment, T1-weighted MRI, and diffusion tensor imaging might be useful to identify early biomarkers in the presymptomatic stage of FTD or amyotrophic lateral sclerosis.","0 (C9orf72 Protein);0 (C9orf72 protein, human);0 (Proteins);Adult;C9orf72 Protein;Cognitive Dysfunction/diagnostic imaging/ pathology/ physiopathology;DNA Repeat Expansion/ genetics;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/diagnostic imaging/genetics/pathology/physiopathology;Gray Matter/diagnostic imaging/ pathology;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Proteins/ genetics;White Matter/diagnostic imaging/ pathology","Papma, J. M.;Jiskoot, L. C.;Panman, J. L.;Dopper, E. G.;den Heijer, T.;Donker Kaat, L.;Pijnenburg, Y. A. L.;Meeter, L. H.;van Minkelen, R.;Rombouts, Sarb;van Swieten, J. C.",2017,Sep 19,,0,
2056,Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment,"Microstructural white matter deterioration is a frequent finding in mild cognitive impairment (MCI), potentially underlying default mode network (DMN) dysfunctioning. Thus far, microstructural damage in MCI has been attributed to Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the role of cerebral small vessel disease (CSVD), received less interest. Here, we used diffusion tensor imaging (DTI) to examine the role of CSVD in microstructural deterioration within the normal appearing white matter (NAWM) in MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31) macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural integrity comparisons within the whole brain NAWM. Secondly, we segmented white matter tracts interconnecting DMN brain regions by means of automated tractography segmentation. We used NAWM DTI measures from these tracts as dependent variables in a stepwise-linear regression analysis, with structural and demographical predictors. Our results indicated microstructural deterioration within the anterior corpus callosum, internal and external capsule and periventricular white matter in MCI patients with CSVD, while in MCI patients without CSVD, deterioration was restricted to the right perforant path, a tract along the hippocampus. Within the full cohort of MCI patients, microstructure within the NAWM of the DMN fiber tracts was affected by the presence of CSVD. Within the cingulum along the hippocampal cortex we found a relationship between microstructural integrity and ipsilateral hippocampal volume and the extent of white matter hyperintensity. In conclusion, we found evidence of CSVD-related microstructural damage in fiber tracts subserving the DMN in MCI.","Aged;Brain/ pathology;Cerebral Small Vessel Diseases/ complications/ pathology;Cohort Studies;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ complications/ pathology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Organ Size;Regression Analysis;White Matter/ pathology","Papma, J. M.;de Groot, M.;de Koning, I.;Mattace-Raso, F. U.;van der Lugt, A.;Vernooij, M. W.;Niessen, W. J.;van Swieten, J. C.;Koudstaal, P. J.;Prins, N. D.;Smits, M.",2014,Jun,10.1002/hbm.22370,0,
2057,Is total brain volume correlated to cognitive function and education in patients with Alzheimer disease?,"This study aimed to correlate whole brain volume measurements with MRI in patients with Alzheimer disease and the same Mini Mental State Examination (MMSE) but different levels of education. We describe the procedure we used to create 3D models of the brain from MRI images in patients with Alzheimer disease and then took volumetric measurements of the whole brain parenchyma. After this procedure we correlated the total brain volume measurements in patients with six or fewer years of education with those who had at least 12 years of education. Twenty patients with Alzheimer disease were examined with MRI. All of them had an MMSE score between 21 and 24 and were classified as mild Alzheimer disease. Ten of the patients had at least six years of education and the remaining ten had more than 12 years of education. The examinations were done by using a Siemens Expert Plus system of 1T and the MR images were studied using an automatic algorithm. The MRI images were segmented into grey, white matter and CSF. We then measured the volume of each component and classified those in each patient in relation to years of education. The whole procedure was completed successfully in 20 patients. After the volumetric study of the total brain volume by calculating separately grey matter, white matter and CSF, we classified the patients and made the correlation between those with six or fewer years of education and those with twelve or more years of study. Correlating the whole brain volume measurements of patients with Alzheimer disease and the same MMSE but different levels of education showed that there is no significant difference between the total brain volume of the two groups of our study.",,"Papapostolou, P.;Goutsaridou, F.;Arvaniti, M.;Emmanouilidou, M.;Tezapsidis, G.;Tsolaki, M.;Tsitouridis, I.",2008,Oct 1,,0,
2058,3D MR Models and Volumetric Measurements of the Brain in Patients with Alzheimer's Disease,"This study aimed to describe the procedure we use to create 3D models of the brain parenchyma from MRI images and calculate the volume of the whole brain and different compartments of the brain in patients with Alzheimer's disease. The utility of the 3D models and volumetric measurements of the whole brain parenchyma and different brain structures is discussed. Thirty-six patients with Alzheimer's disease were examined during the last six months with MRI. Fourteen of them were men and 22 were women. The patients were between 53 and 67 years old. MR images were studied using an automatic algorithm. The images from MRI were segmented and then three-dimensional models of brain were produced to calculate the brain volume and the volume of the white matter, gray matter and CSF separately. The whole procedure was completed successfully in 34 patients. The procedure was unsuccessful in two patients due to movement artifacts in MR images. It is relatively easy to create 3D models of MR images and to obtain volumetric studies. If this procedure is adjusted in patients with Alzheimer's disease, we can provide information more clearly and accurately than single images alone. The information obtained can be used in daily clinical practice such as pharmaceutical treatment planning and results or in basic clinical research.",,"Papapostolou, P.;Arvaniti, M.;Goutsaridou, F.;Emmanouilidou, M.;Tezapsidis, G.;Chondromatidou, S.;Tsolaki, M.;Tsitouridis, I.",2008,Dec 17,,0,
2059,Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial,"BACKGROUND AND PURPOSE: Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD. METHODS: 242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo. RESULTS: 230 patients (121 nimodipine, mean age 75.2+/-6.1; 109 placebo, 75.4+/-6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production (P<0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; chi2 P<0.01) and Global Deterioration Scale (P<0.05). Dropouts and adverse events were all significantly more common among placebo than nimodipine patients, particularly cardiovascular (30 versus 13; RR, 2.26; 95% CI, 1.11 to 4.60) and cerebrovascular events (28 versus 10; RR, 2.48; 95% CI, 1.23 to 4.98), and behavioral disturbances requiring intervention (22 versus 5; RR, 3.88; 95% CI, 1.49 to 10.12). A worst-rank analysis, performed to correct for the effect of the high dropout rate in the placebo group, showed additional significant differences in favor of nimodipine in Set Test and MMSE total scores. CONCLUSIONS: Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.","Dementia, Vascular [prevention & control];Nimodipine [adverse effects] [therapeutic use];Safety;Treatment Outcome;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];adult;article;behavior disorder/si [Side Effect];cardiovascular disease/si [Side Effect];cerebrovascular disease/si [Side Effect];clinical trial;cognition;computer assisted tomography;controlled clinical trial;controlled study;double blind procedure;drug efficacy;drug safety;female;global deterioration scale;heart infarction/si [Side Effect];high risk population;human;hypertension/si [Side Effect];major clinical study;male;mental disease/si [Side Effect];Mini Mental State Examination;multicenter study;multiinfarct dementia/di [Diagnosis];multiinfarct dementia/dt [Drug Therapy];neurologic disease/si [Side Effect];priority journal;randomized controlled trial;rating scale;risk reduction;stroke/si [Side Effect];transient ischemic attack/si [Side Effect];treatment outcome;calcium antagonist/ae [Adverse Drug Reaction];calcium antagonist/ct [Clinical Trial];calcium antagonist/dt [Drug Therapy];calcium antagonist/po [Oral Drug Administration];nimodipine/ae [Adverse Drug Reaction];nimodipine/ct [Clinical Trial];nimodipine/dt [Drug Therapy];nimodipine/po [Oral Drug Administration];placebo;Sr-dementia","Pantoni, L.;Ser, T.;Soglian, A. G.;Amigoni, S.;Spadari, G.;Binelli, D.;Inzitari, D.",2005,,10.1161/01.STR.0000155686.73908.3e,0,
2060,Thrombophilic risk factors and unusual clinical features in three Italian CADASIL patients,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.",,"Pantoni, L.;Sarti, C.;Pescini, F.;Bianchi, S.;Bartolini, L.;Nencini, P.;Basile, A. M.;Lamassa, M.;Kalaria, R. N.;Dotti, M. T.;Federico, A.;Inzitari, D.",2004,November,,0,
2061,Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial,"In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.","Activities of Daily Living;Aged;Aged, 80 and over;Calcium Channel Blockers/adverse effects/*therapeutic use;Dementia, Vascular/*drug therapy/radiography;Female;Humans;Male;Middle Aged;Neuropsychological Tests;*Nimodipine/adverse effects;Tomography, X-Ray Computed;Vasodilator Agents/adverse effects/*therapeutic use","Pantoni, L.;Rossi, R.;Inzitari, D.;Bianchi, C.;Beneke, M.;Erkinjuntti, T.;Wallin, A.",2000,Apr 15,,0,
2062,Effect of Attention Training in Mild Cognitive Impairment Patients with Subcortical Vascular Changes: The RehAtt Study,"BACKGROUND AND OBJECTIVE: Mild cognitive impairment (MCI) patients with small vessel disease (SVD) are at high dementia risk. We tested the effects of cognitive rehabilitation in these patients using the Attention Process Training-II (APT-II) program in a single-blinded, randomized clinical trial. METHODS: Patients were randomized to APT-II or standard care and evaluated at baseline, 6, and 12 months with functional, quality of life, cognitive tests, and resting state functional MRI (rsfMRI). RESULTS: Forty-six patients were enrolled and 43 (mean+/-SD age 75.1+/-6.8) completed the study. No change was seen in functionality and quality of life between treated and non-treated patients. However, the Rey Auditory-Verbal Learning Test immediate recall showed a significant improvement in treated compared to non-treated group (change score 6 versus 12 months: 1.8+/-4.9 and -1.4+/-3.8, p = 0.021; baseline versus 12 months: 3.8+/-6.1 and 0.2+/-4.4, p = 0.032). A higher proportion of treated patients had stable/better evaluation compared to non-treated group on Visual search test (6 versus 12 months: 95% versus 71%, p = 0.038) and Rey-Osterrieth Complex Figure copy (6 versus 12 months: 95% versus 67%, p = 0.027). RsfMRI, performed in a subsample, showed that the difference between follow-up and baseline in synchronization of activity in cerebellar areas was significantly greater in treated than in non-treated patients. CONCLUSION: We were unable to show a significant effect in quality of life or functional status in treated patients with MCI and SVD. However, APT-II produces some beneficial effects in focused attention and working memory and seems to increase activity in brain circuits involved in cognitive processes.",Cerebrovascular disorders;clinical trial;cognitive dysfunction;functional magnetic resonance imaging;rehabilitation,"Pantoni, L.;Poggesi, A.;Diciotti, S.;Valenti, R.;Orsolini, S.;Della Rocca, E.;Inzitari, D.;Mascalchi, M.;Salvadori, E.",2017,,,0,
2063,Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study,"OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.","Activities of Daily Living;Aged;Aged, 80 and over;Cognition Disorders/ etiology/pathology;Cross-Sectional Studies;Female;Humans;Leukoaraiosis/ complications/pathology;Magnetic Resonance Imaging;Male;Motor Skills;Telencephalon/pathology","Pantoni, L.;Poggesi, A.;Basile, A. M.;Pracucci, G.;Barkhof, F.;Chabriat, H.;Erkinjuntti, T.;Ferro, J. M.;Hennerici, M.;O'Brien, J.;Schmidt, R.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Inzitari, D.",2006,Jul,10.1111/j.1532-5415.2006.00798.x,0,
2064,"Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients","OBJECTIVE: To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS: Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. CONCLUSIONS: Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.","Adult;Aged;Brain Infarction/pathology;*CADASIL/complications/genetics/pathology;Cognition Disorders/etiology/pathology;DNA Mutational Analysis;Exons/genetics;Family Health;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Migraine Disorders/pathology;Mutation/*genetics;Receptors, Notch/*genetics;Retrospective Studies;Risk Factors;Stroke/pathology","Pantoni, L.;Pescini, F.;Nannucci, S.;Sarti, C.;Bianchi, S.;Dotti, M. T.;Federico, A.;Inzitari, D.",2010,Jan 5,10.1212/WNL.0b013e3181c7da7c,0,
2065,Cerebrospinal fluid proteins in patients with leucaraiosis: Possible abnormalities in blood-brain barrier function,"Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 ± 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 ± 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l ± 0.11 vs. 0.21 g/l ± 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml ± 1.45 vs. 2.85 mg/100 ml ± 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 ± 0.0027 vs. 0.0058 ± 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 ± 0.0028 vs. 0.0059 ± 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations.",adult;aged;article;blood brain barrier;cerebrospinal fluid;clinical article;controlled study;dementia;female;human;human tissue;male;priority journal;protein analysis;vascular disease,"Pantoni, L.;Inzitari, D.;Pracucci, G.;Lolli, F.;Giordano, G.;Bracco, L.;Amaducci, L.",1993,,,0,
2066,Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function,"Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 +/- 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 +/- 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l +/- 0.11 vs. 0.21 g/l +/- 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml +/- 1.45 vs. 2.85 mg/100 ml +/- 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 +/- 0.0027 vs. 0.0058 +/- 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 +/- 0.0028 vs. 0.0059 +/- 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations.","Aged;Alzheimer Disease/cerebrospinal fluid/metabolism/psychology;*Blood-Brain Barrier;Brain/*radiography;Brain Diseases/cerebrospinal fluid/metabolism/psychology;Cerebrospinal Fluid Proteins/*analysis;Cognition;Dementia/cerebrospinal fluid/metabolism/psychology;Female;Humans;Immunoglobulin G/cerebrospinal fluid;Male;Middle Aged;Serum Albumin/cerebrospinal fluid;*Tomography, X-Ray Computed","Pantoni, L.;Inzitari, D.;Pracucci, G.;Lolli, F.;Giordano, G.;Bracco, L.;Amaducci, L.",1993,Apr,,0,
2067,Abulia and cognitive impairment in two patients with capsular genu infarct,"Background - An internal capsule genu infarct has been rarely reported to cause cognitive impairment and behavioral changes. This clinical picture can be explained on anatomical and functional basis because important subcortical-cortical pathways traverse the internal capsule genu. We report 2 previously non-demented patients who developed acute confusional state, abulia, and moderate cognitive decline after the occurrence of an infarct in the capsular genu. Methods - Clinical, neuropsychological, and MRI evaluation at baseline and 12-month follow-up. Results - Abulia and cognitive impairment were still present 1 year after stroke. In 1 patient there were associated multiple lacunar infarcts and leukoaraiosis. In the other an old small left frontal infarct was also present. In both moderate cortical atrophy co-existed. Conclusions - We hypothesize that co-existing lesions, possibly associated with a sub-clinical reduction of cognitive functions, facilitate the development of a persistent clinically evident mental deficit after the occurrence of an infarct in the capsular genu.",aged;article;capsula interna;case report;clinical feature;cognitive defect;confusion;follow up;functional anatomy;human;infarction;leukoaraiosis;male;mental deficiency;neuroanatomy;neuropsychological test;nuclear magnetic resonance imaging,"Pantoni, L.;Basile, A. M.;Romanelli, M.;Piccini, C.;Sarti, C.;Nencini, P.;Inzitari, D.",2001,,,0,
2068,"Impact of age-related cerebral white matter changes on the transition to disability - The LADIS study: Rationale, design and methodology","Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 ± 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability. Copyright © 2005 S. Karger AG, Basel.",aged;aging;article;brain function;cause of death;cognition;controlled study;daily life activity;dementia;depression;disability;disease course;disease severity;female;follow up;function test;human;leukoaraiosis;longitudinal study;major clinical study;male;methodology;mood;motor performance;nuclear magnetic resonance imaging;prediction;quality of life;vascular disease;white matter,"Pantoni, L.;Basile, A. M.;Pracucci, G.;Asplund, K.;Bogousslavsky, J.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Ferro, J. M.;Hennerici, M.;O'Brien, J.;Scheltens, P.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Inzitari, D.",2005,,,0,
2069,Not-so-silent infarcts,,Alzheimer Disease/*complications;Cerebrovascular Disorders/classification/*complications/pathology;Cognition Disorders/*etiology/pathology;Dementia/*etiology;Humans;Magnetic Resonance Imaging/methods,"Pantoni, L.",2003,Jun,,0,
2070,Genetic and environmental influences of white and gray matter signal contrast: a new phenotype for imaging genetics?,"The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness. Participants were 514 male twins (130 monozygotic, 97 dizygotic pairs, and 60 unpaired individuals) from the Vietnam Era Twin Study of Aging. Ages ranged from 51 to 59 years. Measures of WM/GM contrast and cortical thickness were derived for 66 cortical regions of interest (ROI) using FreeSurfer-based methods. Univariate and bivariate twin analyses were used in order to estimate the heritability of WM/GM contrast, as well as the degree of shared genetic and environmental variance between WM/GM contrast and cortical thickness. WM/GM contrast was found to be significantly heritable in the majority of ROIs. The average heritability across individual ROIs was highest in the occipital lobe (.50), and lowest in the cingulate cortex (.24). Significant phenotypic correlations between WM/GM contrast and cortical thickness were observed for most of the ROIs. The majority of the phenotypic correlations were negative, ranging from ?.11 to ?.54. Of the 66 associations, only 17 significant genetic correlations were found, ranging from ?.16 to ?.34, indicating small amounts of shared genetic variance. The majority of the phenotypic correlations were accounted for by small unique environmental effects common between WM/GM contrast and cortical thickness. These findings demonstrate that like cortical thickness, WM/GM contrast is a genetically influenced brain structure phenotype. The lack of significant genetic correlations with cortical thickness suggests that this measure potentially represents a unique source of genetic variance, one that has yet to be explored by the field of imaging genetics.","Aging/ genetics/ pathology;Brain;Cerebral Cortex/ pathology;Environment;Genetic Association Studies;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Phenotype;Polymorphism, Single Nucleotide/genetics;Twins/ genetics/statistics & numerical data;United States;Veterans/statistics & numerical data;Vietnam Conflict","Panizzon, M. S.;Fennema-Notestine, C.;Kubarych, T. S.;Chen, C. H.;Eyler, L. T.;Fischl, B.;Franz, C. E.;Grant, M. D.;Hamza, S.;Jak, A.;Jernigan, T. L.;Lyons, M. J.;Neale, M. C.;Prom-Wormley, E. C.;Seidman, L.;Tsuang, M. T.;Wu, H.;Xian, H.;Dale, A. M.;Kremen, W. S.",2012,Apr 15,10.1016/j.neuroimage.2012.01.122,0,
2071,Quantitative T2 measurements in juvenile and late infantile neuronal ceroid lipofuscinosis,"Purpose: The two most prevalent forms of neuronal ceroid lipofuscinosis (NCL) are the juvenile form (Batten disease, CLN3) and late infantile form (Jansky-Bielschowsky disease, CLN2). The aim of this study was to compare quantitative T2-values of brain tissue in CLN2 and CLN3 patients with reference values from age-matched normal subjects. Methods: Twenty-three CLN2 (n = 6) and CLN3 (n = 17) patients (m:f = 11:12) underwent MRI examination including a multiecho T2 sequence. Quantitative T2-values were measured in six defined regions of interest (ROIs) in the calculated quantitative T2 maps within the white matter (WM) and gray matter (GM). The extracted quantitative T2-values were compared with reference values from healthy children and young adults. Informed consent was obtained from the patients or their parents for all patients. Results: Statistical analysis revealed elevated quantitative T2-values in nearly all ROIs placed in the WM of the CLN2 patients. In contrast to this finding, no significant differences were found for the quantitative T2-values of the CLN3 patients compared to the age-matched healthy controls in any of the defined WM ROIs. Both groups exhibited no significant alterations of the quantitative T2-values in the GM ROIs compared to the healthy subjects. Conclusion: Alterations of quantitative T2-values in the cerebral WM may not be a reliable sign to confirm the diagnosis in CLN3 patients but could prove valuable for diagnosis confirmation, follow-up examinations, and longitudinal monitoring of the disease progression in CLN2 patients. © 2012 Springer-Verlag Berlin Heidelberg.",adolescent;adult;article;brain development;brain tissue;caudate nucleus;child;clinical article;controlled study;disease course;female;follow up;gray matter;human;informed consent;male;neuroimaging;neuronal ceroid lipofuscinosis;neuronal ceroid lipofuscinosis late infantile type;nuclear magnetic resonance imaging;preschool child;quantitative analysis;reference value;school child;statistical analysis;white matter,"Paniagua Bravo, A.;Forkert, N. D.;Schulz, A.;Löbel, U.;Fiehler, J.;Ding, X.;Sedlacik, J.;Rosenkranz, M.;Goebell, E.",2013,,,0,
2072,Lymhomatosis cerebri - A rare cause of leukoencephalopathy,"Background: Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma. Clinically it presents usually as rapidly progressive dementia and is accompanied by extensive white matter changes in magnetic resonance imaging (MRI). Case description: A 49-year-old immuno-competent male who complained of dull diffuse headache, rapidly deteriorated in higher functions over a 6 month period. On examination he was globally declined in cognitive functions and had papilledema. MRI showed extensive white matter lesions. He became temporarily alert, and attentive after a course of parenteral steroids. However within three weeks he relapsed and a wedge biopsy of the brain revealed histopathology consistent with lymphomatosis cerebri. Conclusion: The differential diagnosis of diffuse white matter diseases is constantly expanding. In the background of a rapidly progressing subcortical dementia and extensive white matter disease, neoplastic disorders of the brain especially lymphomatosis cerebri should be considered. Early tissue diagnosis is important for specific treatment and interventions. © 2010 Elsevier B.V. All rights reserved.",,"Pandit, L.;Chickabasaviah, Y.;Raghothaman, A.;Mustafa, S.;Vasudevan, A.",2010,15,,0,
2073,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: An imaging mimic of multiple sclerosis: A report of two cases,"Objective and Importance: To describe the imaging findings of two cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mimicking multiple sclerosis. Clinical Presentation and Intervention: Two cases presenting with neurological signs and symptoms were referred for magnetic resonance imaging (MRI) evaluation of the brain. Case 1 was a 36-year-old female patient presenting with recurrent headaches and recent onset numbness in the fingers of the right hand. Neurological examination showed a mild sensory deficit in the right hand. Case 2 was a 31-year-old female patient presenting with attacks of right-sided numbness of the face and body. The neurological examination revealed a sensory loss in the face and brisk deep tendon reflexes. Routine MRI sequences showed two types of lesions in both cases: 'punctate' hyperintense lesions on T (2)-weighted images (T(2)WI)/fluid-attenuated inversion recovery (FLAIR) images, hypointense on T(1)-weighted images (T (1)WI) and 'diffuse' white matter lesions, hyperintense on T (2)WI/FLAIR sequences and isointense to hypointense on T(1)WI. All lesions showed no contrast enhancement. Both cases were previously clinically and radiologically diagnosed as multiple sclerosis. There was a strong family history consistent with recurrent infarctions in other family members of both patients. Both cases were later diagnosed as CADASIL by skin biopsy/genetic linkage studies and follow-up. Conclusion: The cases showed that CADASIL causes stroke-like episodes in adults and can mimic multiple sclerosis on imaging. Clinical evaluation and MRI findings allow a differentiation of the two entities. Copyright © 2006 S. Karger AG.",,"Pandey, T.;Abubacker, S.",2006,August,,0,
2074,CNS intravascular lymphoma: An underappreciated cause of rapidly progressive dementia,"Intravascular lymphoma is a rare subtype of extranodal large cell non-Hodgkin's lymphoma that is usually seen in the elderly. It can occasionally present with neurological symptoms in the form of dementia, focal neurological deficit and seizure. Diagnosis is difficult because of non-speci fic clinical manifestation. We report a case of a 38-year-old woman presenting with rapidly progressive dementia and seizure. MRI of the brain showed bilateral diffuse involvement of cortex and subcortical white matter. Brain biopsy disclosed the aetiological confirmation of intravascular B-cell lymphoma. The patient was treated with monthly cyclophosphamide, doxorubicin, vincristine and prednisolone regimen, but unfortunately, she died after two chemotherapy cycles. So, high index of suspicion is warranted to diagnose and treat the condition early to have a better outcome. Copyright 2014 BMJ Publishing Group. All rights reserved.",alanine aminotransferase;antibiotic agent;aspartate aminotransferase;CD20 antibody;cyclophosphamide;doxorubicin;ferritin;fibrinogen;gamma glutamyltransferase;infusion fluid;lactate dehydrogenase;methylprednisolone;phenytoin;prednisolone;vincristine;abdominal radiography;adult;article;artificial ventilation;behavior disorder;blood cell count;brain biopsy;brain radiography;case report;cerebrospinal fluid analysis;contrast enhancement;Creutzfeldt Jakob disease;death;dementia;differential diagnosis;electroencephalography;encephalitis;female;Glasgow coma scale;Hashimoto encephalopathy;histopathology;hospital infection;human;human tissue;image analysis;image processing;image quality;large cell lymphoma;learning disorder;liver function test;long term memory;magnetic resonance angiography;memory disorder;mental deterioration;multiple cycle treatment;neurologic examination;nuclear magnetic resonance imaging;paraneoplastic neuropathy;priority journal;protein blood level;psychomotor disorder;rapidly progressive dementia;seizure;Sjoegren syndrome;splenomegaly;systemic lupus erythematosus;tonic clonic seizure;treatment response,"Panda, A. K.;Malik, S.",2014,,,0,
2075,"Multi-infarct dementia and Alzheimer disease, contribution of cerebral circulation ultrasonography to pathogenesis and differential diagnosis. Value of microembolisation","OBJECTIVES: Dementias are one of the most serious health and socioeconomic issues. Multi-infarct dementia (MID) and Alzheimer s type dementia (AD) exhibit differences in cerebrovascular blood flow velocity profiles and in presence of microemboli, detected by transcranial Doppler sonography. MATERIAL AND METHODS: A group of 77 persons was divided into 4 subgroups: 1. subgroup of patients with MID (n=19; 10 male and 9 female, mean age was 74.32+/-8.30 years); 2. subgroup of patients with AD (n=19; 11 male and 8 female, mean age was 70.37+/-87.85 years); 3. subgroup of patients with hypertension (n=19; 11 male and 8 female, age adjusted) and 4. sex and age adjusted control group (CG) of 20 persons without hypertension or other serious risk factors. The duplex ultrasonographic examination of extracranial and intracranial circulation was preceded by neurologic, neuropsychological and psychiatric examination. The presence of microemboli was determined using Multi Dop X2 device (maker DWL), 60 minutes monitoring. All patients underwent brain computer tomography (CT) or magnetic resonance imaging (MRI). RESULTS: We found significantly higher incidence (68.4%, p=0.5267) of asymptomatic microemboli in ACM in the group of patients with MID compared to the AD group, the group of patients with hypertension and CG. CONCLUSION: The occurrence of ""asymptomatic"" emboli in the middle cerebral artery in patients with multi-infarct dementia is higher in the current study. Although these microemboli do not cause immediate symptoms, the evidence suggests, that they may be a risk factor for cognitive impairment, especially for multi-infarct dementia.",,"Pancak, J.;Wagnerova, H.;Skultety Szarazova, A.;Blaho, A.;Durovsky, O.;Durovska, J.",2016,,,0,
2076,CADASIL in a family from north-west India,We here with report a family with two sibs having history of recurrent familial stroke. Neuroimaging revealed diffuse hyperintense signals in subcortical white matter and basal ganglia on MR images in younger sib suggestive of cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leucoencephalopathy (CADASIL). The diagnosis was further strengthened on skin biopsy showing presence of PAS positive granules with thickening of dermal vessels.,,"Panagariya, A.;Sharma, B.;Shubhakaran",2004,Jul,,0,
2077,Evaluation of (11) C TAZA for amyloid beta plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT,"OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Abeta plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11) C]TAZA), for binding to Abeta plaques in postmortem human brain (AD and normal control (NC)). METHODS: Radiosyntheses of [(11) C]TAZA, related [(11) C]Dalene ((11) C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11) C]PIB were carried out using [(11) C]methyltriflate prepared from [(11) C]CO2 and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Abeta plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. RESULTS: The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/mumol. TAZA had an affinity, Ki = 0.84 nM and was five times more potent than PIB. [(11) C]TAZA bound specifically to Abeta plaques present in AD brains with gray matter to white matter ratios >20. [(11) C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11) C]TAZA and [(11) C]PIB. [(11) C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. CONCLUSION: [(11) C]TAZA exhibited high binding to Abeta plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. Synapse, 2016. (c) 2016 Wiley Periodicals, Inc. Synapse 70:163-176, 2016. (c) 2016 Wiley Periodicals, Inc.",,"Pan, M. L.;Mukherjee, M. T.;Patel, H. H.;Patel, B.;Constantinescu, C. C.;Mirbolooki, M. R.;Liang, C.;Mukherjee, J.",2016,Apr,10.1002/syn.21893,0,
2078,Rett syndrome: (1)H spectroscopic imaging at 4.1 Tesla,"Rett syndrome, a neurodevelopmental disorder predominantly affecting girls, is characterized by regression of psychomotor development, communication dysfunction, and hand stereotypies. Brain morphologic studies demonstrate increased neuronal packing density and reduced dendritic arborizations, suggesting an arrest or interruption of normal maturation. Numerous neurotransmitter systems have been implicated. Among these, cerebrospinal fluid glutamate levels are elevated and glutamate receptors, particularly in putamen, are reduced. Therefore, (1)H spectroscopy at 4.1 Tesla was used to evaluate glutamate, creatine, and N-acetylaspartate in six girls with Rett syndrome and four normal sibling controls. The ratio of creatine to N-acetylaspartate was significantly elevated in white matter, primarily reflecting reduced N-acetylaspartate levels, and normal in gray matter. The glutamate to N-acetylaspartate ratio was elevated in gray matter and normal in white matter. These findings are consistent with previous neuropathologic and neurochemical findings and indicate the feasibility of imaging these metabolites in vivo.",,"Pan, J. W.;Lane, J. B.;Hetherington, H.;Percy, A. K.",1999,August,,0,
2079,CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts,"BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.","Adaptor Proteins, Signal Transducing;Adult;Antigens, CD/analysis;Antigens, Differentiation, Myelomonocytic/analysis;Bone Cysts/genetics/ pathology;Dementia/genetics/ pathology;Female;Follow-Up Studies;Frontal Lobe/ pathology;Homozygote;Humans;Immunoenzyme Techniques;Lipodystrophy/genetics/ pathology;Magnetic Resonance Imaging;Male;Membrane Proteins;Microglia/chemistry/pathology;Middle Aged;Molecular Sequence Data;Mutation;Receptors, Immunologic/genetics;Talus/pathology","Paloneva, J.;Autti, T.;Raininko, R.;Partanen, J.;Salonen, O.;Puranen, M.;Hakola, P.;Haltia, M.",2001,Jun 12,,0,
2080,Association between subcortical lesions and behavioral and psychological symptoms in patients with Alzheimer's disease,"BACKGROUND/AIMS: The most devastating features of Alz-heimer's disease (AD) are often the behavioral and psychological symptoms in dementia (BPSD). There is controversy as to whether subcortical lesions contribute to BPSD. The aim of this study was to examine the relationship between BPSD and subcortical lesions (white-matter lesions and lacunes) in AD. METHODS: CT or MRI from 259 patients with mild-to-moderate AD were assessed with the Age-Related White Matter Changes scale. Linear measures of global and temporal atrophy and Mini-Mental State Examination scores were used to adjust for AD pathology and disease severity in logistic regression models with the BPSD items delusions, hallucinations, agitation, depression, anxiety, apathy and irritability. RESULTS: Lacunes in the left basal ganglia were associated with delusions (OR 2.57, 95% CI 1.21-5.48) and hallucinations (OR 3.33, 95% CI 1.38-8.01) and lacunes in the right basal ganglia were associated with depression (OR 2.13, 95% CI 1.01-4.51). CONCLUSION: Lacunes in the basal ganglia resulted in a 2- to 3-fold increased risk of delusions, hallucinations and depression, when adjusting for cognition and atrophy. This suggests that basal ganglia lesions can contribute to BPSD in patients with AD, independently of the AD process.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/pathology/psychology/radiography;Basal Ganglia/pathology;Basal Ganglia Diseases/complications/pathology/*psychology;Behavioral Symptoms;Delusions/*complications/pathology;Depression/*complications/pathology;Female;Frontal Lobe/pathology;Hallucinations/*complications/pathology;Humans;Longitudinal Studies;Male;Parietal Lobe/pathology","Palmqvist, S.;Sarwari, A.;Wattmo, C.;Bronge, L.;Zhang, Y.;Wahlund, L. O.;Nagga, K.",2011,,10.1159/000335778,0,
2081,Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis,"Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the ""disconnection syndrome"" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a ""disconnection syndrome."" Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD.",Ad;connectomics;disconnection syndrome;probabilistic tractography;resting state networks,"Palesi, F.;Castellazzi, G.;Casiraghi, L.;Sinforiani, E.;Vitali, P.;Gandini Wheeler-Kingshott, C. A.;D'Angelo, E.",2016,,10.3389/fnins.2016.00380,0,
2082,White matter/gray matter contrast changes in chronic and diffuse traumatic brain injury,"Signal-intensity contrast of T1-weighted magnetic resonance imaging scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as Alzheimer's disease. After severe traumatic brain injury (TBI), progressive structural changes occur in white (WM) and gray matter (GM). In the current study, we assessed the signal-intensity contrast of GM and WM in patients with diffuse TBI in the chronic stage to (1) characterize the regional pattern of WM/GM changes in intensity contrast associated with traumatic axonal injury, (2) evaluate possible associations between this measure and diffusion tensor image (DTI)/fractional anisotropy (FA) for detecting WM damage, and (3) investigate the correlates of both measures with cognitive outcomes. Structural T1 scans were processed with FreeSurfer software to identify the boundary and calculate the WM/GM contrast maps. DTIs were processed with the FMRIB software library to obtain FA maps. The WM/GM contrast in TBI patients showed a pattern of reduction in almost all of the brain, except the visual and motor primary regions. Global FA values obtained from DTI correlated with the intensity contrast of all associative cerebral regions. WM/GM contrast correlated with memory functions, whereas FA global values correlated with tests measuring memory and mental processing speed. In conclusion, tissue-contrast intensity is a very sensitive measure for detecting structural brain damage in chronic, severe and diffuse TBI, but is less sensitive than FA for reflecting neuropsychological sequelae, such as impaired mental processing speed.","Adult;Brain/ pathology;Brain Injuries/complications/ pathology/psychology;Chronic Disease;Cognition Disorders/etiology/psychology;Diffusion Tensor Imaging;Female;Glasgow Coma Scale;Humans;Image Processing, Computer-Assisted;Male;Neuropsychological Tests;Young Adult","Palacios, E. M.;Sala-Llonch, R.;Junque, C.;Roig, T.;Tormos, J. M.;Bargallo, N.;Vendrell, P.",2013,Dec 1,10.1089/neu.2012.2836,0,
2083,[Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Krakow. I. Project to test exposure to risk factors for cardiovascular disease in the studied sample] Zaburzenia funkcji poznawczych a czynniki ryzyka chorob ukladu krazenia. Projekt CASCADE Krakow. Czesc I: Projekt badania oraz wyjsciowe narazenie na czynniki ryzyka chorob ukladu krazenia w badanej probie,"Dementia is found in a small percent of general population but remains a significant problem in the elderly population. Little is known whether prevention of dementia in the elderly is possible. Some evidence exists that both vascular dementia and Alzheimer's type dementia are related to cardiovascular disease risk factors. The main goal of the CASCADE Krakow Project is to study the relation between the exposure to cardiovascular disease risk factors in the middle age and cognitive impairment and cerebral white matter lesions in old age. Project CASCADE Krakow is an independent part of the international project CASCADE, which is carried out in 11 research centres from 9 countries. Polish part of the study includes a longitudinal observation of the sample screened earlier in POL-MONICA Krakow Project, which was selected from population of residents of rural province (Tarnobrzeg Voivodship). Studied sample are 1318 persons, for whom cardiovascular disease risk factors were measured in 1983-84 and who completed at least 64 years in 1997. Two-stage examination was designed. In the first stage collection of the following data was designed: socio-economic factors, history of cardiovascular disease, perceived health, blood pressure and cognitive function assessment using Mini-Mental State Examination (MMSE) procedure. In the second stage (sub-sample of 300 persons included) the following procedures were designed: detailed neuro-psychological testing, neurolo-gical examination, MRI, determination of total- and HDL-cholesterol and determination of apoE isoforms. There were 625 (47%) men and 693 (53%) women selected for the first stage. Out of them 128 (43%) men and 172 (57%) women were selected for the second stage. There were no important differences in age, education, health status and exposure to cardiovascular disease risk factors between the studied groups in the baseline assessment. However, there were important differences between men and women. Compared to men, women had lower education (higher than elementary education in 17% and 9% respectively), more frequent obesity (respectively 12% and 36%), hypertension (respectively 57% and 71%) and hyperlipoproteinemia (respectively 17% and 30%) but lower smoking rate (respectively 53% and 4%). Integration of neuropsychological testing and neuroimaging with the epidemiological approach to risk factors could contribute to better understanding of the mechanisms on which the disease affects the brain morphology and functions. The results of CASCADE and CASCADE Krakow projects will contribute also to the development of the strategies of medical care and management of the cognitive impairment in the elderly.",Aged;Cardiovascular Diseases/ epidemiology;Cognition Disorders/diagnosis/ epidemiology/prevention & control;Comorbidity;Dementia/epidemiology/prevention & control;Educational Status;Female;Health Status;Humans;Hyperlipoproteinemias/epidemiology;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Obesity/epidemiology;Poland/epidemiology;Risk Assessment;Sex Distribution;Smoking/epidemiology;Socioeconomic Factors,"Pajak, A.;Kawalec, E.;Szczudlik, A.",1998,,,0,
2084,Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Kraków. I. Project to test exposure to risk factors for cardiovascular disease in the studied sample,"Dementia is found in a small percent of general population but remains a significant problem in the elderly population. Little is known whether prevention of dementia in the elderly is possible. Some evidence exists that both vascular dementia and Alzheimer's type dementia are related to cardiovascular disease risk factors. The main goal of the CASCADE Kraków Project is to study the relation between the exposure to cardiovascular disease risk factors in the middle age and cognitive impairment and cerebral white matter lesions in old age. Project CASCADE Kraków is an independent part of the international project CASCADE, which is carried out in 11 research centres from 9 countries. Polish part of the study includes a longitudinal observation of the sample screened earlier in POL-MONICA Kraków Project, which was selected from population of residents of rural province (Tarnobrzeg Voivodship). Studied sample are 1318 persons, for whom cardiovascular disease risk factors were measured in 1983-84 and who completed at least 64 years in 1997. Two-stage examination was designed. In the first stage collection of the following data was designed: socio-economic factors, history of cardiovascular disease, perceived health, blood pressure and cognitive function assessment using Mini-Mental State Examination (MMSE) procedure. In the second stage (sub-sample of 300 persons included) the following procedures were designed: detailed neuro-psychological testing, neurolo-gical examination, MRI, determination of total- and HDL-cholesterol and determination of apoE isoforms. There were 625 (47%) men and 693 (53%) women selected for the first stage. Out of them 128 (43%) men and 172 (57%) women were selected for the second stage. There were no important differences in age, education, health status and exposure to cardiovascular disease risk factors between the studied groups in the baseline assessment. However, there were important differences between men and women. Compared to men, women had lower education (higher than elementary education in 17% and 9% respectively), more frequent obesity (respectively 12% and 36%), hypertension (respectively 57% and 71%) and hyperlipoproteinemia (respectively 17% and 30%) but lower smoking rate (respectively 53% and 4%). Integration of neuropsychological testing and neuroimaging with the epidemiological approach to risk factors could contribute to better understanding of the mechanisms on which the disease affects the brain morphology and functions. The results of CASCADE and CASCADE Kraków projects will contribute also to the development of the strategies of medical care and management of the cognitive impairment in the elderly.",aged;article;cardiovascular disease;cognitive defect;comorbidity;dementia;educational status;female;health status;human;hyperlipoproteinemia;hypertension;male;middle aged;neuropsychological test;nuclear magnetic resonance imaging;obesity;Poland;risk assessment;sex ratio;smoking;socioeconomics,"Pajak, A.;Kawalec, E.;Szczudlik, A.",1998,,,0,
2085,[Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Krakow. I. Project to test exposure to risk factors for cardiovascular disease in the studied sample],"Dementia is found in a small percent of general population but remains a significant problem in the elderly population. Little is known whether prevention of dementia in the elderly is possible. Some evidence exists that both vascular dementia and Alzheimer's type dementia are related to cardiovascular disease risk factors. The main goal of the CASCADE Krakow Project is to study the relation between the exposure to cardiovascular disease risk factors in the middle age and cognitive impairment and cerebral white matter lesions in old age. Project CASCADE Krakow is an independent part of the international project CASCADE, which is carried out in 11 research centres from 9 countries. Polish part of the study includes a longitudinal observation of the sample screened earlier in POL-MONICA Krakow Project, which was selected from population of residents of rural province (Tarnobrzeg Voivodship). Studied sample are 1318 persons, for whom cardiovascular disease risk factors were measured in 1983-84 and who completed at least 64 years in 1997. Two-stage examination was designed. In the first stage collection of the following data was designed: socio-economic factors, history of cardiovascular disease, perceived health, blood pressure and cognitive function assessment using Mini-Mental State Examination (MMSE) procedure. In the second stage (sub-sample of 300 persons included) the following procedures were designed: detailed neuro-psychological testing, neurolo-gical examination, MRI, determination of total- and HDL-cholesterol and determination of apoE isoforms. There were 625 (47%) men and 693 (53%) women selected for the first stage. Out of them 128 (43%) men and 172 (57%) women were selected for the second stage. There were no important differences in age, education, health status and exposure to cardiovascular disease risk factors between the studied groups in the baseline assessment. However, there were important differences between men and women. Compared to men, women had lower education (higher than elementary education in 17% and 9% respectively), more frequent obesity (respectively 12% and 36%), hypertension (respectively 57% and 71%) and hyperlipoproteinemia (respectively 17% and 30%) but lower smoking rate (respectively 53% and 4%). Integration of neuropsychological testing and neuroimaging with the epidemiological approach to risk factors could contribute to better understanding of the mechanisms on which the disease affects the brain morphology and functions. The results of CASCADE and CASCADE Krakow projects will contribute also to the development of the strategies of medical care and management of the cognitive impairment in the elderly.",Aged;Cardiovascular Diseases/*epidemiology;Cognition Disorders/diagnosis/*epidemiology/prevention & control;Comorbidity;Dementia/epidemiology/prevention & control;Educational Status;Female;Health Status;Humans;Hyperlipoproteinemias/epidemiology;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Obesity/epidemiology;Poland/epidemiology;Risk Assessment;Sex Distribution;Smoking/epidemiology;Socioeconomic Factors,"Pajak, A.;Kawalec, E.;Szczudlik, A.",1998,,,0,
2086,Patterns of neuropsychological impairment in mild dementia: a comparison between Alzheimer's disease and multi-infarct dementia,"The objective was to investigate the clinical and psychometric differences between patients with dementia of Alzheimer type (DAT) and patients with multi-infarct dementia (MID), matched for age, sex, education, and severity. Sixteen patients with DAT, 16 patients with MID, and 30 healthy individuals, were drawn from a longitudinal study on aging and dementia. Subjects with medical or previous mental disorders were excluded. DAT and controls with focal brain abnormalities on magnetic resonance imaging (MRI) were excluded. Diagnosis of dementia was carried out according to DSM-III-R criteria. Dementia severity was staged using the Clinical Dementia Rating (CDR) scale, and only patients with a score of 0.5-1 on CDR were studied. The main outcome measures were quantitative clinical scales of the assessment of global mental status, depression and anxiety, as well as a wide battery of neuropsychological tests for the evaluation of executive/conceptual functions and memory, as well as attention verbal ability, and visuospatial skill functions. The performance of demented patients compared to normal controls was affected on all measurements except for depression and anxiety. DAT patients showed compared to MID patients a greater extent of impairment on tasks assessing verbal comprehension and memory while MID patients were more significantly impaired on measures of frontal lobe functioning. Clinically matched DAT and MID patients show a differential pattern of neuropsychological impairment when studied in an early stage of dementia and with a mild degree of severity. Such patterns might be of value for the development of clinical diagnostic criteria.","Aged;Alzheimer Disease/ complications/diagnosis/ physiopathology;Brain/ physiopathology;Cognition Disorders/ complications/diagnosis;Dementia, Multi-Infarct/ complications/diagnosis/ physiopathology;Educational Status;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Severity of Illness Index","Padovani, A.;Di Piero, V.;Bragoni, M.;Iacoboni, M.;Gualdi, G. F.;Lenzi, G. L.",1995,Dec,,0,
2087,Database integration of protocol-specific neurological imaging datasets,"For many years now, Magnetic Resonance Innovations (MR Innovations), a magnetic resonance imaging (MRI) software development, technology, and research company, has been aggregating a multitude of MRI data from different scanning sites through its collaborations and research contracts. The majority of the data has adhered to neuroimaging protocols developed by our group which has helped ensure its quality and consistency. The protocols involved include the study of: traumatic brain injury, extracranial venous imaging for multiple sclerosis and Parkinson's disease, and stroke. The database has proven invaluable in helping to establish disease biomarkers, validate findings across multiple data sets, develop and refine signal processing algorithms, and establish both public and private research collaborations. Myriad Masters and PhD dissertations have been possible thanks to the availability of this database. As an example of a project that cuts across diseases, we have used the data and specialized software to develop new guidelines for detecting cerebral microbleeds. Ultimately, the database has been vital in our ability to provide tools and information for researchers and radiologists in diagnosing their patients, and we encourage collaborations and welcome sharing of similar data in this database.",Alzheimer disease;article;brain hemorrhage;cerebrovascular accident;chronic kidney failure;clinical protocol;cohort analysis;computer interface;software;consciousness;contrast enhancement;data base;dementia;diabetes mellitus;file transfer protocol;human;imaging and display;migraine;multiple sclerosis;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;Parkinson disease;phlebography;picture archiving and communication system;priority journal;radiologist;secure socket layer;signal processing;traffic accident;traumatic brain injury;vertigo;virtual private network,"Pacurar, E. E.;Sethi, S. K.;Habib, C.;Laze, M. O.;Martis-Laze, R.;Haacke, E. M.",2016,,10.1016/j.neuroimage.2015.04.066,0,
2088,Is there a correlation between the pineal gland calcification and migraine?,"OBJECTIVE: The pineal gland calcifications have been associated with some diseases such as cerebral infarction, Alzheimer's disease and intracerebral hemorrhage while most cases are considered idiopathic and physiologic. However, there are limited data in the current literature about the association of pineal calcification and migraine. Our aim was to evaluate this association between migraine and pineal calcification by computed tomography of the brain. PATIENTS AND METHODS: In our study, we assessed the computed tomography images of patients, who referred to the neurology outpatient clinic with the complaint of headache and were diagnosed with migraine without aura based according to 2004 criteria of the International Headache Society. 503 migraine patients and 500 control subjects without migraine diagnosis were included in this study. RESULTS: When migraine and control groups were compared by pineal calcification, the rates were determined as 80, 6% and 55% in migraine and control group, respectively. The difference was statistically significant (p < 0.001). In addition, it was seen that pineal calcifications, detected in migraine patients, did not show age-related increase. CONCLUSIONS: According to our data, we can point that pineal calcification may be associated with migraine.",,"Ozlece, H. K.;Akyuz, O.;Ilik, F.;Huseyinoglu, N.;Aydin, S.;Can, S.;Serim, V. A.",2015,Oct,,0,
2089,Klüver-Bucy-like syndrome and frontal symptoms following cerebrovascular disease,"We present a case with frontal lobe symptoms and Klüver-Bucy-like syndrome following subarachnoid hemorrhage and hydrocephaly. Klüver-Bucy syndrome is a rare neurobehavioral condition characterized by placidity, visual agnosia, hypersexuality, hyperorality, and hypermetamorphosis (the tendency to react to or to touch every visual stimulus). The syndrome is usually associated with lesions of the amygdala or its pathways, and it occurs after head trauma, anoxia-ischemic encephalopathy, herpes simplex encephalitis, and Reye 's syndrome. A 45-year-old right-handed female patient, who developed hydrocephaly after meningitis due to bilateral middle cerebral artery aneurysm surgery presented to our psychiatry clinic with various behavioral and emotional changes. In her psychiatric examination, increased and disinhibited speech, perseveration, placidity, impaired go/no go task performance, and hyperphagia were observed. The patient was treated with risperidone 0.5 mg/day. Magnetic resonance imaging (MRI) of the brain showed encephalomalacic-gliotic changes in the anterior superior medial temporal lobe (including bilateral amygdala), hydrocephalus, bilateral abnormal signal intensity in the white matter of the frontal region, and bilateral infarction in the centrum semiovale. Symptoms, such as placidity (loss of anger and fear) and altered dietary habits are some of the clinical features of Klüver-Bucy syndrome, whereas disinhibition and perseveration are associated with prefrontal cortex dysfunction.",,"Ozdemir, H.;Rezaki, M.",2007,2007,,0,
2090,Homocysteine and vitamin B12 levels related to MRI white matter abnormalities in Parkinson's disease dementia,,"Basal Ganglia/*pathology;Female;Hippocampus/*pathology;Homocysteine/*blood;Humans;Male;Nerve Fibers/*pathology;Parkinson Disease/*pathology;Supranuclear Palsy, Progressive/*pathology","Ozcan, O.;Cosar, A.",2013,,10.1159/000345414,0,
2091,CADASIL with a novel NOTCH3 mutation (Cys478Tyr),"Recently, an increasing number of NOTCH3 mutations have been described to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Japanese family, who were found to possess a novel NOTCH3 mutation. The proband only had chronic headache, and her mother had previously suffered a minor stroke. Although the patients' clinical symptoms were mild, their distinctive magnetic resonance imaging (MRI) features suggested CADASIL. Genetic analysis revealed that both patients had a novel heterozygous NOTCH3 mutation (p.Cys478Tyr) leading to stereotypical cysteine loss. The present finding suggests that genetic testing for NOTCH3 mutations in patients with distinctive MRI features, even if the symptoms are as mild as chronic headache, should help to broaden the mutational and clinical spectrum of CADASIL.",,"Ozaki, K.;Irioka, T.;Ishikawa, K.;Mizusawa, H.",2015,1,,0,
2092,Capgras syndrome in vascular dementia: Recognition memory and visual processing,Face recognition memory and the processing of tachistoscopically presented visual stimuli were investigated in two subjects with Capgras syndrome coexisting with vascular dementia. The subjects were both found to have impairment of face recognition memory as well as impairment of verbal recognition memory. One of the subjects was found to have a reversal of the usual advantage of the right hemisphere for processing perceptual stimuli which were visually similar. The failure to find this reversed pattern in the other subject was attributed to CT scan evidence of an old anterior infarct of his left hemisphere. The neuropsychological basis of Capgras syndrome is discussed in the light of these findings.,aged;article;brain infarction;Capgras syndrome;case report;computer assisted tomography;female;human;left hemisphere;male;multiinfarct dementia;neuropsychology;recognition;vision,"Oyebode, F.;Edelstyn, N. M. J.;Patel, A.;Riddoch, M. J.;Humphreys, G. W.",1996,,,0,
2093,The Combined Effect of Neuropsychological and Neuropathological Deficits on Instrumental Activities of Daily Living in Older Adults: a Systematic Review,"To date, studies have consistently demonstrated associations between either neuropsychological deficits or neuroanatomical changes and instrumental activities of daily living (IADL) in aging. Only a limited number of studies have evaluated morphological brain changes and neuropsychological test performance concurrently in relation to IADL in this population. As a result, it remains largely unknown whether these factors independently predict functional outcome. The current systematic review intended to address this lack of information by reviewing the literature on older adults, incorporating studies that examined e.g., normal aging, but also stroke or dementia patients. A comprehensive search of databases (Pubmed, Embase, Medline, Web of Science, PsycINFO) and reference lists was performed, focusing on papers in the English language that examined the combined effect of neuropsychological and neuroanatomical factors on IADL in samples of adults with an average age above 50. In total, 58 potential articles were identified; 20 were included in the review. The results show that especially neuropsychological variables (primarily memory and executive functions) independently predict IADL. Although some unique predictive value of brain morphological changes, such as hippocampal atrophy, was found, support for the importance of white matter changes was limited. However, the results of the studies reviewed are diverse, and appear to be at least partially determined by the variables included. For example, studies were less likely to find an independent effect of cognition if they solely employed a cognitive screening instrument. This indicates that a structured examination of neuroanatomical and neuropsychological correlates of IADL in different patient populations is warranted.",,"Overdorp, E. J.;Kessels, R. P.;Claassen, J. A.;Oosterman, J. M.",2016,Mar,10.1007/s11065-015-9312-y,0,
2094,Independent component analysis-based identification of covariance patterns of microstructural white matter damage in Alzheimer's disease,"The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer's disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Case-Control Studies;Female;Humans;Male;Middle Aged;Radiographic Image Interpretation, Computer-Assisted/ methods;White Matter/ pathology","Ouyang, X.;Chen, K.;Yao, L.;Wu, X.;Zhang, J.;Li, K.;Jin, Z.;Guo, X.",2015,,10.1371/journal.pone.0119714,0,
2095,Simultaneous changes in gray matter volume and white matter fractional anisotropy in Alzheimer's disease revealed by multimodal CCA and joint ICA,"The prominent morphometric alterations of Alzheimer's disease (AD) occur both in gray matter and in white matter. Multimodal fusion can examine joint information by combining multiple neuroimaging datasets to identify the covariant morphometric alterations in AD in greater detail. In the current study, we conducted a multimodal canonical correlation analysis and joint independent component analysis to identify the covariance patterns of the gray and white matter by fusing structural magnetic resonance imaging and diffusion tensor imaging data of 39 AD patients (23 males and 16 females, mean age: 74.91+/-8.13years) and 41 normal controls (NCs) (20 males and 21 females, mean age: 73.97+/-6.34years) derived from the Alzheimer's Disease Neuroimaging Initiative database. The results revealed 25 joint independent components (ICs), of which three joint ICs exhibited strong links between the gray matter volume and the white matter fractional anisotropy (FA) and significant differences between the AD and NC group. The joint IC maps revealed that the simultaneous changes in the gray matter and FA values primarily involved the following areas: (1) the temporal lobe/hippocampus-cingulum, (2) the frontal/cingulate gyrus-corpus callosum, and (3) the temporal/occipital/parietal lobe-corpus callosum/corona radiata. Our findings suggest that gray matter atrophy is associated with reduced white matter fiber integrity in AD and possibly expand the understanding of the neuropathological mechanisms in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Diffusion Tensor Imaging;Female;Gray Matter/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;White Matter/ pathology","Ouyang, X.;Chen, K.;Yao, L.;Hu, B.;Wu, X.;Ye, Q.;Guo, X.",2015,Aug 20,10.1016/j.neuroscience.2015.06.031,0,
2096,Validation of the semi-quantitative static SUVR method for [18F]-AV45 PET by pharmacokinetic modeling with an arterial input function,"Increased brain uptake of [18F]-AV45 visualized by PET is a key biomarker for Alzheimer's disease (AD). The standardized uptake value ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min [18F]-AV45 (291 +/- 67 MBq) and 1-min [15O]-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD dementia, 15 amnestic mild cognitive impairment (aMCI) and 10 cognitively healthy controls (HC). [18F]-AV45 VT was determined from two-tissue compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min p.i., using either cerebellar gray matter (SUVRCB) or whole subcortical white matter (SUVRWM) as reference. Additionally, whole cerebellum, pons, centrum semiovale and a composite region were examined as alternative references. Blood flow was quantified by [15O]-H2O SUV. Data are presented as mean +/- standard error of the mean (SEM). Results: There was rapid metabolization of [18F]-AV45 with only 35% of unchanged parent remaining at 10 minutes. Compared to VT, differences in cortical Abeta-load between aMCI and AD were overestimated by SUVRWM (+4 +/- 2%) and underestimated by SUVRCB (-10 +/- 2%). VT correlated better with SUVRWM (Pearson's r: from 0.63 for posterior cingulate to 0.89 for precuneus, p < 0.0001) than with SUVRCB (Pearson's r: from 0.51 for temporal lobe (p = 0.002) to 0.82 for precuneus (p < 0.0001)) in all tested regions. Correlation results for the alternative references were in-between those for CB and WM. [15O]-H2O data showed that blood flow was decreased in AD compared to aMCI in cortical regions (-5 +/- 1%) and in the reference regions (CB: -9 +/- 8%, WM: -8 +/- 8%). Conclusion: Increased brain uptake of [18F]-AV45 assessed by the simplified static SUVR protocol does not truly reflect Abeta load. However, SUVRWM is better correlated with VT and more closely reflects VT differences between aMCI and AD than SUVRCB.",Alzheimer's disease;Molecular Imaging;Pet;Radiotracer Tissue Kinetics;[<sup>18</sup>F]-AV45;amyloid;cerebral perfusion;kinetic modeling,"Ottoy, J.;Verhaeghe, J.;Niemantsverdriet, E.;Wyffels, L.;Somers, C.;De Roeck, E.;Struyfs, H.;Soetewey, F.;Deleye, S.;Van den Bossche, T.;Van Mossevelde, S.;Ceyssens, S.;Versijpt, J.;Stroobants, S.;Engelborghs, S.;Staelens, S.",2017,Mar 23,,0,
2097,A SPECT imaging study of MRI white matter hyperintensity in patients with degenerative dementia,"We investigated the correlation between cortical perfusion and white matter hyperintensities on magnetic resonance images (MRI) of patients with dementia. The study included 40 subjects, each of whom had undergone both MRI and single-photon emission computed tomography (SPECT) studies as part of their diagnostic evaluation for degenerative dementia. Two neuroradiologists rated the MRI films for severity of periventricular white matter changes on a 0-5 point scale and severity of subcortical white matter changes on a 0-4 point scale. Twelve regions of interest from association cortex were sampled for the semiquantitative analysis of SPECT images. No relationship was found between these global MRI ratings and semiquantitative or qualitative SPECT findings. Dementia severity as measured by the Mini-Mental State Examination and the Clinical Dementia Rating was significantly correlated with SPECT, whereas age was significantly correlated with MRI ratings, particularly in the periventricular regions. These data support the view that cortical SPECT abnormalities are not associated with global MRI abnormalities in the subcortical and periventricular regions of patients with a clinical picture of degenerative dementia.","Aged;Alzheimer Disease/complications/ diagnosis;Brain/ radionuclide imaging;Cognition Disorders/diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Severity of Illness Index;Tomography, Emission-Computed, Single-Photon","Ott, B. R.;Faberman, R. S.;Noto, R. B.;Rogg, J. M.;Hough, T. J.;Tung, G. A.;Spencer, P. K.",1997,Nov-Dec,,0,
2098,Diffuse tract damage in the hemispheric deep white matter may correlate with global cognitive impairment and callosal atrophy in patients with extensive leukoaraiosis,"BACKGROUND AND PURPOSE: Patients with extensive leukoaraiosis are at high risk for vascular dementia. However, these patients exhibit variable severity of global cognitive impairment correlating with callosal atrophy. We hypothesized that callosal atrophy may reflect the severity of HDWM tract damage, which may explain global cognitive impairment. The purpose of this study was to evaluate HDWM tract damage by DTI and to investigate whether HDWM tract damage is associated with callosal atrophy and global cognitive impairment, in patients with extensive leukoaraiosis. MATERIALS AND METHODS: Twenty-four consecutive outpatients with extensive leukoaraiosis were enrolled prospectively. The patients underwent cognitive evaluation and 3T MR imaging. The intercorrelation between cognitive score, DA of the HDWM, callosal DA, and callosal volume was analyzed statistically. The correlation of the cognitive score with DA of the HDWM and the corpus callosum was also evaluated by voxel-based analyses by using TBSS. RESULTS: The patients' MMSE scores varied from 10 to 30 (mean, 25.1 +/- 6.0). Reduced DA of the HDWM, reduced callosal DA, and callosal atrophy intercorrelated significantly. All of these parameters showed a significant correlation with global cognitive impairment. TBSS analyses showed a significant correlation between MMSE score decline and reduced DA in the diffuse HDWM and the corpus callosum. CONCLUSIONS: In patients with extensive leukoaraiosis, atrophy and reduced DA of the corpus callosum may indicate diffuse HDWM tract damage, which may explain global cognitive impairment and development of vascular dementia.","Aged;Aged, 80 and over;Atrophy/pathology;Cognition Disorders/ complications/ diagnosis;Corpus Callosum/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Leukoaraiosis/ complications/ pathology;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic","Otsuka, Y.;Yamauchi, H.;Sawamoto, N.;Iseki, K.;Tomimoto, H.;Fukuyama, H.",2012,Apr,10.3174/ajnr.A2853,0,
2099,"Normal pressure hydrocephalus manifesting as transient prosopagnosia, topographical disorientation, and visual objective agnosia","Usually, dementia, gait disturbance and urinary incontinence are an integral part of the clinical presentation of normal pressure hydrocephalus (NPH). However, NPH with transient visual cognitive disorders has not been reported previously. We herein describe an extremely rare case of NPH that presented with transient visual cognitive disorders and long lasting visual memory disturbances that subsided after CSF shunting. A 38-years-old man developed transient prosopagnosia, topographical disorientation, color vision disturbance, and visual objective agnosia that progressed over 5 years. Magnetic resonance images showed ventriculomegaly with ischemic lesions in the paraventricular deep white matter. ECD-SPECT showed a reduction of the cerebral blood flow (CBF) in the periventricular deep white matter. Three months after CSF shunting, the radiological findings normalized with dramatic improvement of the extremely rare symptoms. © 2003 Published by Elsevier Ltd.",,"Otani, N.;Nawashiro, H.;Ishihara, S.;Fukui, S.;Katoh, H.;Tsuzuki, N.;Ohnuki, A.;Miyazawa, T.;Shima, K.",2004,April,,0,
2100,Relationship between apathy and diffusion tensor imaging metrics of the brain in Alzheimers disease,"Objective Alzheimer's disease (AD) research has largely concentrated on the study of cognitive decline, but the associated behavioral and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. Apathy is the most common neuropsychiatric manifestation in AD. Clinical, multimodal neuroimaging studies and pathologic studies of apathy in AD have suggested an association with frontal dysfunction but without a definitive localization. In this study, we examined the association between apathy and white matter integrity using diffusion tensor imaging (DTI). Methods Twenty-one AD patients underwent DTI and neuropsychiatric and cognitive assessments. All fractional anisotropy (FA) maps were normalized to the standard space, and the association between the apathy scale and DTI metrics were evaluated voxel basically. Results Statistical parametric mapping analysis showed that there were statistically negative correlations between the apathy scale and FA values in the right anterior cingulate, right thalamus, and bilateral parietal regions using age, Mini-Mental State Examination score and sex as nuisance variables. Conclusions Apathy in AD is associated with impaired white matter integrity in the anterior cingulate and medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating limbic dysfunction and related neuronal circuits in the neurobiology of apathy in AD. Copyright © 2011 John Wiley & Sons, Ltd.",,"Ota, M.;Sato, N.;Nakata, Y.;Arima, K.;Uno, M.",2012,July,,0,
2101,Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study,Ischemic leukoaraiosis is a consistent concomitant of vascular dementia. Conventional MRI provides little information about underlying white matter tract disruption and correlates poorly with cognitive dysfunction. Diffusion tensor MRI may provide better markers of tract integrity. Changes in the normal-appearing white matter were demonstrated in 30 patients with ischemic leukoaraiosis compared with 17 age-matched control subjects. These changes correlated with executive dysfunction assessed by the Wisconsin Card Sorting Test.,"Aged;Brain/*pathology;Brain Ischemia/*pathology/psychology;Dementia, Vascular/*pathology/psychology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","O'Sullivan, M.;Summers, P. E.;Jones, D. K.;Jarosz, J. M.;Williams, S. C.;Markus, H. S.",2001,Dec 26,,0,
2102,Diffusion tensor imaging of thalamus correlates with cognition in CADASIL without dementia,"BACKGROUND: Executive dysfunction is an early feature in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and may progress to a subcortical dementia. The mechanism of cognitive impairment is incompletely understood, and correlations with T2 lesion volumes are not strong. Diffusion tensor imaging (DTI) may provide a better index of white matter tract damage. Previous DTI studies in CADASIL demonstrated abnormalities in normal-appearing white matter, thalamus, and putamen and correlations with the Mini-Mental State Examination (MMSE). OBJECTIVE: S: To determine whether DTI abnormalities could be identified in nondemented patients with CADASIL and whether these correlated particularly strongly with executive function. METHODS: Eighteen CADASIL subjects underwent DTI and cognitive assessment, including tests of several aspects of executive function. DTI was also performed on 12 age-matched control subjects. RESULTS: Mean diffusivity was increased in white matter lesions, normal-appearing white matter, and normal-appearing gray matter (thalamus, putamen, and globus pallidus). A composite score of executive function correlated with diffusivity in both normal-appearing gray matter (r = -0.73, p = 0.002) and white matter (r = -0.68, p = 0.004). The strongest correlation for gray matter was for the thalamus (r = -0.66, p = 0.004); this remained after controlling for age, gender, and T2 lesion volumes. Correlations with MMSE were much weaker, and there was no correlation between T2 lesion volume and the executive function score (r = -0.29, p = 0.27). CONCLUSIONS: Abnormalities of normal-appearing white and deep gray matter are present in nondemented CADASIL patients, and these DTI measurements correlate particularly strongly with executive function.",Adult;CADASIL/ physiopathology;Cognition;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Putamen/pathology;Thalamus/ pathology,"O'Sullivan, M.;Singhal, S.;Charlton, R.;Markus, H. S.",2004,Mar 9,,0,
2103,Frequency of subclinical lacunar infarcts in ischemic leukoaraiosis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: Small vessel cerebrovascular disease is an important cause of vascular cognitive impairment. It is usually sporadic but also occurs secondary to the genetic disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Recurrent lacunar stroke is a characteristic feature, although symptomatic events are relatively rare, making large numbers necessary for evaluation of potential therapies. Diffusion-weighted imaging is sensitive to acute ischemic lesions and differentiates them from chronic infarcts. Detection of asymptomatic lacunar infarcts with diffusion-weighted imaging is a potential surrogate marker for treatment trials. In this study, the frequency of asymptomatic new lesions in ischemic leukoaraiosis and CADASIL was determined as a step toward assessing the potential of this technique as a surrogate marker of disease activity. METHODS: Fifty patients with sporadic small vessel disease and 19 patients with CADASIL underwent diffusion-weighted imaging. All had been asymptomatic for 3 months before imaging. Diffusion-weighted images were screened by two raters for new lesions; lesions were confirmed as recent by a visible reduction of diffusivity on the corresponding apparent diffusion coefficient maps. RESULTS: Recent ischemic lesions were identified in four patients with sporadic small vessel disease (8.0%) and two patients with CADASIL (10.5%). CONCLUSION: Asymptomatic new lesions are found in cases of sporadic small vessel disease and CADASIL. The frequency of new lesions suggests that this approach has a potential role as a surrogate marker in therapeutic trials that warrants further investigation.","Adult;Aged;Aged, 80 and over;Brain Infarction/ diagnosis/epidemiology;Brain Ischemia/ diagnosis/epidemiology;Cerebral Arterial Diseases/ diagnosis/genetics;Cerebral Infarction/diagnosis/epidemiology;Cohort Studies;Dementia, Multi-Infarct/diagnosis/epidemiology;Dementia, Vascular/ diagnosis/epidemiology;Diffusion Magnetic Resonance Imaging;Dystonic Disorders;Female;Great Britain/epidemiology;Humans;Male;Middle Aged;Mutation;Prevalence","O'Sullivan, M.;Rich, P. M.;Barrick, T. R.;Clark, C. A.;Markus, H. S.",2003,Aug,,0,
2104,Hippocampal volume is an independent predictor of cognitive performance in CADASIL,"Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n=144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampal volume (HV) correlated with age (r=-0.33, p<0.001), brain volume (r=0.39, p<0.001) and lacunar lesion volume (r=-0.23, p=0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272+/-333 mm(3) versus 2642+/-349 mm(3), p<0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r=0.30, p<0.001), MDRS (r=0.40, p<0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.","CADASIL/complications/*diagnosis/*pathology;*Cognition;Cognition Disorders/*diagnosis;Female;Hippocampus/*pathology;Humans;Imaging, Three-Dimensional/*methods;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Organ Size;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic","O'Sullivan, M.;Ngo, E.;Viswanathan, A.;Jouvent, E.;Gschwendtner, A.;Saemann, P. G.;Duering, M.;Pachai, C.;Bousser, M. G.;Chabriat, H.;Dichgans, M.",2009,Jun,10.1016/j.neurobiolaging.2007.09.002,0,
2105,Brief cognitive assessment for patients with cerebral small vessel disease,"BACKGROUND: Cerebral small vessel disease is a common cause of cognitive impairment and vascular dementia. The cognitive deficit differs from that in Alzheimer's disease, with greater executive/attentional dysfunction and relatively intact episodic memory. OBJECTIVE: To develop brief assessment tools that are better adapted to the neuropsychological profile of cerebral small vessel disease. METHODS: 32 subjects with ischaemic leukoaraiosis (history of lacunar stroke and leukoaraiosis on MRI), aged 50 to 84 years, and 17 age and education matched controls had a brief executive assessment, which took 20 minutes to administer, and a wide range of additional tests. The ability of the brief executive assessment to discriminate between groups-both individually and in combination-was evaluated and compared with that of the whole battery. RESULTS: The brief executive assessment provided good sensitivity and specificity for identifying subjects with ischaemic leukoaraiosis (sensitivity 88%, specificity 88%, using the optimal combination of scores). The best individual tests were trail making and digit symbol, which were both far more sensitive than the mini-mental state examination (MMSE). The ability to discriminate between groups was maintained in subjects with MMSE > 27 and across the whole age range. The brief executive assessment performed well compared with the whole battery, with additional tests accounting for only a further 12% of between-group variance. CONCLUSIONS: The brief executive assessment was sensitive to deficits found in ischaemic leukoaraiosis and discriminated them from the cognitive effects of healthy aging. The assessment has potential for bedside use and as a cognitive end point for clinical trials.","Aged;Aged, 80 and over;Attention/physiology;Brain/*blood supply/*pathology;Brain Ischemia/*complications/*pathology;Capillaries/*pathology;Cognition Disorders/diagnosis/*etiology;Dementia, Vascular/diagnosis/etiology;Educational Status;Female;Humans;Leukoaraiosis/*complications/*pathology;Magnetic Resonance Imaging;Male;Memory Disorders/diagnosis/*etiology;Middle Aged;*Neuropsychological Tests;Sensitivity and Specificity;Severity of Illness Index","O'Sullivan, M.;Morris, R. G.;Markus, H. S.",2005,Aug,10.1136/jnnp.2004.045963,0,
2106,Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis,"BACKGROUND: Cerebral small vessel disease is a common cause of vascular dementia. Both discrete lacunar infarcts and more diffuse ischaemic changes, seen as confluent high signal (leukoaraiosis) on T2 weighted magnetic resonance imaging (MRI), occur. However, there is a weak correlation between T2 lesion load and cognitive impairment. Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage. OBJECTIVES: To determine whether DTI measures are correlated more strongly with cognitive performance than lesion load on T2 weighted images, and whether these correlations are independent of conventional MRI parameters. METHODS: 36 patients with ischaemic leukoaraiosis (leukoaraiosis plus a previous lacunar stroke) and 19 healthy volunteers underwent DTI, conventional MRI, and neuropsychological assessment. RESULTS: On DTI, diffusivity was increased both within lesions and in normal appearing white matter. Mean diffusivity of normal appearing white matter correlated with full scale IQ (r = -0.46, p = 0.009) and tests of executive function. These correlations remained significant after controlling for age, sex, brain volume, and T1/T2 lesion volumes. No significant correlation was identified between T2 lesion load and IQ or neuropsychological scores. Of conventional measures, brain volume correlated best with cognitive function. CONCLUSIONS: Diffusion tensor measurements correlate better with cognition than conventional MRI measures. They may be useful in monitoring disease progression and as a surrogate marker for treatment trials. The findings support the role of white matter damage and disruption of white matter connections in the pathogenesis of cognitive impairment in cerebral small vessel disease.","Aged;Aged, 80 and over;Brain/pathology;Brain Infarction/ pathology;Brain Ischemia/ complications/ radiography;Cognition Disorders/ etiology;Dementia, Vascular/physiopathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Predictive Value of Tests;Sensitivity and Specificity","O'Sullivan, M.;Morris, R. G.;Huckstep, B.;Jones, D. K.;Williams, S. C.;Markus, H. S.",2004,Mar,,0,
2107,MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited, autosomal dominant condition caused by mutations of the Notch3 gene. Affected individuals have migraine, mood disturbance, and recurrent strokes, often progressing to subcortical dementia and premature death. MRI findings include focal lacunar infarcts and diffuse T2-weighted hyperintensity, or leukoaraiosis. However, such findings are seen much more commonly in patients with cardiovascular risk factors, particularly hypertension, where they are believed to represent cerebral small vessel disease. No previous study has sought to identify specific radiologic markers of CADASIL. METHODS: MRI scans from 20 consecutive patients with CADASIL and 20 patients with sporadic leukoaraiosis due to presumed small-vessel disease were compared using the previously validated semiquantitative MRI rating scale devised by Scheltens et al. Analysis was blinded to clinical category. RESULTS: Scores for hyperintensities of the temporal white matter and external capsule-insula region were significantly higher in patients with CADASIL. Hyperintensity confined to the pole of the temporal lobe was a characteristic finding in CADASIL, occurring in 19 patients with CADASIL but no patients with ischemic leukoaraiosis. Involvement of the external capsule, though less specific, was seen early in the disease course. In a few patients with CADASIL, involvement of the corpus callosum was observed. CONCLUSIONS: Temporal pole hyperintensity is a radiologic marker of CADASIL. Involvement of the external capsule and corpus callosum are also characteristic findings that may help to distinguish the disease.","Adult;Aged;Aged, 80 and over;Dementia, Multi-Infarct/*pathology;Humans;Magnetic Resonance Imaging;Middle Aged;Temporal Lobe/*pathology","O'Sullivan, M.;Jarosz, J. M.;Martin, R. J.;Deasy, N.;Powell, J. F.;Markus, H. S.",2001,Mar 13,,0,
2108,Damage within a network of white matter regions underlies executive dysfunction in CADASIL,"OBJECTIVE: To identify the important sites of white matter disruption that underpin executive dysfunction in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic model of pure subcortical vascular disease. METHODS: The anatomic pattern of correlation between tissue integrity and executive function was explored with diffusion tensor imaging (DTI), which provides quantitative measures of tissue integrity. Eighteen nondemented patients with CADASIL underwent DTI and cognitive assessment. DTI was normalized to a standard template and correlations assessed at every voxel across the brain with Statistical Parametric Mapping with cluster-level correction for multiple comparisons. RESULTS: For executive tasks, correlations were found in a number of discrete regions in the white matter of the frontal lobes. A distinct, nonoverlapping pattern of correlation was seen for verbal memory. Significant independent correlations remained in some regions after co-varying for age and IQ. CONCLUSIONS: Different cognitive functions correlate with structural integrity at different sites in the white and subcortical gray matter. The distribution of regions correlating specifically with executive function provides clues to the organization of the relevant cognitive networks and their important white matter projections. The cingulum bundle is one candidate tract that may carry anteroposterior connections important for executive processes.","Adult;CADASIL/diagnosis/ physiopathology/psychology;Cerebral Arteries/pathology/physiopathology;Cerebral Cortex/ pathology/physiopathology;Cognition Disorders/ diagnosis/etiology/ physiopathology;Diffusion Magnetic Resonance Imaging;Frontal Lobe/pathology/physiopathology;Humans;Memory Disorders/diagnosis/etiology/physiopathology;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology/physiopathology;Neural Pathways/pathology/physiopathology;Neuropsychological Tests;Predictive Value of Tests;Verbal Behavior/physiology;Wallerian Degeneration/etiology/pathology/physiopathology","O'Sullivan, M.;Barrick, T. R.;Morris, R. G.;Clark, C. A.;Markus, H. S.",2005,Nov 22,10.1212/01.wnl.0000184480.07394.fb,0,
2109,Jargonagraphia in a case of frontotemporal dementia,Jargonagraphia is known to occur after discrete brain lesions but not in primary degenerative dementia. We report a patient with frontotemporal dementia who developed jargonagraphia and nonfluent aphasia. Written output was graphically preserved but consisted of short words intermingled with abstruse neologisms. MRI showed predominant right frontotemporal cortical atrophy accompanied by white matter hyperintensities in the right anterior subcallosal periventricular region. Diagnosis and MRI were corroborated by extensive neuropathological findings obtained 8 months later. The agraphia in this case is discussed with reference to both specific macroscopic and microscopic pathoanatomical lesions. We suggest that jargonagraphia can appear in frontotemporal dementia depending on the localization of lesions. © 2001 Academic Press.,adult;agraphia;aphasia;article;brain atrophy;case report;clinical feature;diagnostic imaging;follow up;frontotemporal dementia;histology;human;image analysis;jargonagraphia;male;neuropathology;nomenclature;nuclear magnetic resonance imaging;symptom;white matter;writing,"Östberg, P.;Bogdanovic, N.;Fernaeus, S. E.;Wahlund, L. O.",2001,,,0,
2110,A case of hypersomnia due to bilateral thalamic stroke,"Bilateral thalamic infarction (BTI) can present as sleep-like coma without focal neurological signs which can lead to delay in the diagnosis. Due to the diagnostic challenge, treatment is often delayed. The early use of DWI-MRI in suspected cases can help in the early diagnosis and treatment.",aged;brain ischemia;case report;cognitive defect;computer assisted tomography;dementia;diffusion weighted imaging;early diagnosis;female;human;hypersomnia;metabolic encephalopathy;note;priority journal;sleep arousal disorder;yawning,"Osman, M.;Abdalla, A.;Al-Qasmi, M.;Bachuwa, G.",2017,,10.1002/ccr3.1145,0,
2111,SPECT for differential diagnosis of dementia and correlation of rCBF with cognitive impairment,"99mTc-HM-PAO single photon emission computed tomography (SPECT) was used to image 30 patients referred for the assessment of dementia. SPECT images revealed various patterns of regional cerebral perfusion (rCBF) in the subgroups of patients with the clinical diagnoses of Alzheimer's disease (AD, n = 14), Pick's disease (n = 1), and multi-infarct dementia (n = 7). In three patients, SPECT clarified the clinical differential diagnostic possibilities. Using a relative rCBF quantification technique, the relationship between specific cognitive impairments and rCBF in the AD patients was determined. There was a significant correlation between language impairment and left hemisphere hypoperfusion, whereas, apraxia correlated with hypoperfusion in the left parietal region. Thus, HM-PAO SPECT is useful as an aid in the differential diagnosis of dementia and the technique of relative rCBF quantification with SPECT may contribute to the understanding of the clinico-anatomical relations of cognitive deficits in dementia.","Aged;Alzheimer Disease/physiopathology/radiography/ radionuclide imaging;Brain/blood supply/radiography/ radionuclide imaging;Cerebrovascular Circulation;Cognition Disorders/ physiopathology/radiography/radionuclide imaging;Dementia/physiopathology/radiography/ radionuclide imaging;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Organotechnetium Compounds;Oximes;Regional Blood Flow;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Osimani, A.;Ichise, M.;Chung, D. G.;Pogue, J. M.;Freedman, M.",1994,May,,0,
2112,Mild phenotype in Pelizaeus-Merzbacher disease caused by a PLP1-specific mutation,"We present the case of a 26. year-old man who developed normally until he began having difficulty walking at age 12. He subsequently became unable to stand at 15. years old and exhibited mental regression and generalized tonic convulsions by age 20. Magnetic resonance imaging revealed incomplete myelination of cerebral white matter, which resembled that of Pelizaeus-Merzbacher disease. By sequencing the proteolipid protein 1 (PLP1) gene, we found a novel mutation (c.352_353delAG (p.Gly130fs)) in the latter half of exon 3 (exon 3B) that is spliced out in the DM20 isoform. Exon 3B mutations are known to cause a mild phenotype since they do not disturb DM20 production. Mutations that truncate PLP1 correlate with a mild phenotype by activating the nonsense-mediated decay mechanism that specifically detects and degrades mRNAs containing a premature termination codon. This attenuates the production of toxic mutant PLP1. The very mild presentation in the present case seems to be derived from the unique nature of the mutation, which preserves DM20 production and decreases mutant PLP1. © 2009 Elsevier B.V.",,"Osaka, H.;Koizume, S.;Aoyama, H.;Iwamoto, H.;Kimura, S.;Nagai, J. I.;Kurosawa, K.;Yamashita, S.",2010,October,,0,
2113,"Small vessel disease, but neither amyloid load nor metabolic deficit, is dependent on age at onset in Alzheimer's disease","BACKGROUND: There is controversy concerning whether Alzheimer's disease (AD) with early onset is distinct from AD with late onset with regard to amyloid pathology and neuronal metabolic deficit. We hypothesized that compared with patients with early-onset AD, patients with late-onset AD have more comorbid small vessel disease (SVD) contributing to clinical severity, whereas there are no differences in amyloid pathology and neuronal metabolic deficit. METHODS: The study included two groups of patients with probable AD dementia with evidence of the AD pathophysiologic process: 24 patients with age at onset <60 years old and 36 patients with age at onset >70 years old. Amyloid deposition was assessed using carbon-11-labeled Pittsburgh compound B positron emission tomography, comorbid SVD was assessed using magnetic resonance imaging, and neuronal metabolic deficit was assessed using fluorodeoxyglucose positron emission tomography. Group differences of global and regional distribution of pathology were explored using region of interest and voxel-based analyses, respectively, carefully controlling for the influence of dementia severity, apolipoprotein E genotype, and in particular SVD. The pattern of cognitive impairment was determined using z scores of the subtests of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery. RESULTS: Patients with late-onset AD showed a significantly greater amount of SVD. No statistically significant differences in global or regional amyloid deposition or neuronal metabolic deficit between the two groups were revealed. However, when not controlling for SVD, subtle differences in fluorodeoxyglucose uptake between early-onset AD and late-onset AD groups were detectable. There were no significant differences regarding cognitive functioning. CONCLUSIONS: Age at onset does not influence amyloid deposition or neuronal metabolic deficit in AD. The greater extent of SVD in late-onset AD influences the association between neuronal metabolic deficit and clinical symptoms.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/ complications/genetics/ metabolism/radionuclide imaging;Amyloid/ metabolism;Apolipoproteins E/genetics;Benzothiazoles/pharmacokinetics;Brain/pathology/radionuclide imaging;Female;Fluorodeoxyglucose F18/pharmacokinetics;Humans;Male;Metabolic Diseases/etiology/radionuclide imaging;Middle Aged;Vascular Diseases/ etiology/radionuclide imaging","Ortner, M.;Kurz, A.;Alexopoulos, P.;Auer, F.;Diehl-Schmid, J.;Drzezga, A.;Forster, S.;Forstl, H.;Perneczky, R.;Sorg, C.;Yousefi, B. H.;Grimmer, T.",2015,Apr 15,10.1016/j.biopsych.2014.01.019,0,
2114,White matter disease: Imaging findings and differential diagnosis,,,"Ortiz, O.;Lustrin, E.;Baadh, A. S.",2012,2012,,0,
2115,Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease,"While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory-motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory-motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non-CAG-driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory-motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non-CAG-driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. Hum Brain Mapp 37:4615–4628, 2016. © 2016 Wiley Periodicals, Inc.",adult;article;brain size;CAG repeat;controlled study;cortical thickness (brain);electrophysiology;female;follow up;functional magnetic resonance imaging;functional neuroimaging;human;Huntington chorea;major clinical study;male;middle aged;motor performance;nuclear magnetic resonance scanner;premotor cortex;priority journal;sensory cortex;tractography;white matter;Philips Achieva;Siemens TIM Trio,"Orth, M.;Gregory, S.;Scahill, R. I.;Mayer, I. S. M.;Minkova, L.;Klöppel, S.;Seunarine, K. K.;Boyd, L.;Borowsky, B.;Reilmann, R.;Bernhard Landwehrmeyer, G.;Leavitt, B. R.;Roos, R. A. C.;Durr, A.;Rees, G.;Rothwell, J. C.;Langbehn, D.;Tabrizi, S. J.",2016,,10.1002/hbm.23332,0,
2116,"Brain microbleeds, amyloid plaques, intellectual deterioration, and arterial stiffness",,C reactive protein;aging;Alzheimer disease;amyloidosis;arterial stiffness;brain blood flow;brain blood vessel;brain disease;brain hemorrhage;brain infarction;cognitive defect;comparative study;deterioration;endothelium cell;heart left right shunt;human;hydrostatic pressure;inflammation;intellectual impairment;letter;lung circulation;nuclear magnetic resonance imaging;priority journal;pulse pressure;pulse wave;recumbency;senile plaque;sitting;sleep;standing;white matter,"O'Rourke, M. F.",2008,,,0,
2117,Ophthalmologic manifestations of acquired immune deficiency syndrome- associated progressive multifocal leukoencephalopathy,"Purpose: Progressive multifocal leukoencephalopathy (PML) is increasingly described as a late complication of the acquired immune deficiency syndrome (AIDS). The purpose of this study is to evaluate retrospectively the ophthalmologic, clinical, and investigational aspects of AIDS-associated PML. Methods: The authors evaluated ten patients in whom ophthalmologic manifestations developed in the course of AIDS-associated PML. Findings at clinical examination and their progression over time, neuroimaging correlates, the results of pathologic investigation, and visual outcomes were reviewed. Results: Progressive multifocal leukoencephalopathy was the AIDS- defining illness in six of ten patients. Homonymous visual field defects were the presenting symptom in three patients and detected in six patients overall. Occipital blindness developed in one patient. Cerebellar signs and brain stem nuclear and supranuclear palsies also were common. Confluent white matter lesions with increased intensity on T2-weighted magnetic resonance imaging were supratentorial in seven patients and infratentorial in three patients. With incomplete data, the median survival time was 3 months from PML onset. Histopathologic confirmation of PML diagnosis was available for nine of the ten patients. Conclusions: The development of progressive retrochiasmal visual field defects, supranuclear and nuclear cranial nerve palsies, or nystagmus ataxia in the relatively young patient should alert the ophthalmologist to the possibility of PML, particularly in the presence of long-tract central nervous system signs or dementia. Progressive multifocal leukoencephalopathy will often be human immunodeficiency virus associated. Human immunodeficiency virus encephalopathy, cerebral toxoplasmosis, lymphoma, and infarction need to be discriminated. Effective therapy is required urgently for this devastating disease.",,"Ormerod, L. D.;Rhodes, R. H.;Gross, S. A.;Crane, L. R.;Houchin, K. W.",1996,1996,,0,
2118,The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study,"The form and distribution of MRI abnormalities in 114 patients with clinically definite multiple sclerosis (MS) have been compared with observations on 53 apparently healthy individuals, 129 patients with isolated focal neurological lesions with which MS often presents (51 patients with optic neuritis, 44 with isolated brainstem lesions and 34 with isolated spinal cord syndromes) and 105 patients with disorders which may be confused clinically or radiologically with MS. The latter comprised 55 patients with cerebral vascular disease (including 7 cases of dementia with diffuse white matter disease), 24 with degenerative ataxic disorders, 8 with cerebellar tonsillar ectopia, 7 with sarcoidosis and 11 with a variety of other disorders. Periventricular abnormalities were found in all but 2 patients with MS and discrete white matter lesions in all but 12. Characteristically the periventricular changes in MS were irregular in outline. Periventricular abnormalities which were often milder and of smooth outline were seen in 37/55 patients with cerebral vascular disease, 9/24 with cerebellar degeneration, 5/7 with sarcoidosis and in 2/3 apparently healthy individuals over the age of 60. The appearances in the 7 cases of dementia resembled those with advanced MS. Cerebellar and/or brainstem atrophy characteristic of the cerebellar degenerations, in the absence of white matter abnormalities, was helpful in making the distinction from MS. Congenital anomalies and tumours in the region of the brainstem and foramen magnum were readily shown. More than half the patients with symptoms attributable to isolated focal neurological lesions had additional lesions at presentation. MS cannot be diagnosed in these cases at presentation, but repeat scans after 5 to 20 months in 25 patients with optic neuritis and 10 with clinically isolated brainstem lesions have shown new lesions in 7 (20%). The patients with new lesions fulfil the criteria for clinically probable MS (Poser et al., 1983). Measurements of T(1) and T(2) in vivo permitted the distinction of acute from chronic brainstem lesions. There werre quantitative differences in T(1) and T(2) between the normal appearing white matter in MS and normal brain. Studies of postmortem brains provided convincing evidence that the MRI abnormalities in MS correspond with plaques. Evidence is a adduced to support the view that an important source of the abnormal NMR signals in acute lesions is oedema, and in chronic lesions is gliosis; demyelination per se is unlikely to make an important contribution.",,"Ormerod, I. E. C.;Miller, D. H.;McDonald, W. I.;Du Boulay, E. P. G. H.;Rudge, P.;Kendall, B. E.;Moseley, I. F.;Johnson, G.;Tofts, P. S.;Halliday, A. M.;Bronstein, A. M.;Scaravilli, F.;Harding, A. E.;Barnes, D.;Zilkha, K. J.",1987,1987,,0,
2119,Progressive multifocal leukoencephalopathy-remission with cytarabine,"A 51-year-old women who was in complete remission from non-Hodgkin's lymphoma, developed a rapidly progressive dementia. Progressive multifocal leukoencephalopathy (PML) was diagnosed on the basis of a rising antibody titre to JC polyomavirus in cerebro-spinal fluid and serum and the presence of diffuse white matter changes on magnetic resonance imaging. She was treated initially with intravenous cytarabine and showed minimal improvement. Rapid improvement occurred when intrathecal cytarabine was added and the patient is in complete remission from both lymphoma and PML 20 months later.",,"O'Riordan, T.;Daly, P. A.;Hutchinson, M.;Shattock, A. G.;Gardner, S. D.",1990,1990,,0,
2120,"Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white-matter abnormalities","The authors report unusual presentations of members of an Irish family with familial AD due to an E280G mutation in exon 8 of presenilin-1. One had spastic paraparesis and white matter abnormalities on cranial MRI. A sibling had an internuclear ophthalmoplegia, spastic-ataxic quadriparesis, and ""cotton-wool plaques"" with amyloid angiopathy on brain biopsy. Another affected sibling also had MRI white matter abnormalities. The MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels.",presenilin 1;adult;Alzheimer disease;amino acid substitution;article;ataxia;brain biopsy;brain blood vessel;brain ischemia;case report;clinical feature;exon;female;gene mutation;human;human tissue;internuclear ophthalmoplegia;leukoencephalopathy;male;nuclear magnetic resonance imaging;priority journal;quadriplegia;senile plaque;sibling;spastic paraplegia;vascular amyloidosis;white matter,"O'Riordan, S.;McMonagle, P.;Janssen, J. C.;Fox, N. C.;Farrell, M.;Collinge, J.;Rossor, M. N.;Hutchinson, M.",2002,,,0,
2121,"Classifying Alzheimer's disease, Lewy body dementia, and normal controls using 3D texture analysis in magnetic resonance images","Dementia is an evolving challenge in society and early intervention is important. The ability to distinguish between different dementia and non-dementia early in course may be essential for successful patient care. Magnetic resonance (MR) imaging may aid as a noninvasive method to increase prediction accuracy. In this work we explored the use of two different 3D local binary pattern (LBP) texture features extracted from T1 MR images of the brain combined with a random forest classifier in an attempt to discern patients with Alzheimer's disease (AD), Lewy body dementia (LBD), and normal controls (NC). Analysis were conducted in areas with white matter lesions (WML) and normal appearing white matter (NAWM). We also calculated correlations between texture features and cognition measured by mini mental state examination (MMSE) controlling for age. Additionally, two different methods for handling the imbalanced data problem were tested, namely cost-sensitive classification and resampling of the data using the synthetic minority oversampling technique (SMOTE). Four different classification tasks were extensively tested, a three-class problem: AD vs. LBD vs. NC, a two-class problem: NC vs. AD, a two-class problem NC vs. LBD, and a two-class problem: AD vs. LBD. Results from 10 folds nested cross validation are reported as mean accuracy, precision, and recall with standard deviation in brackets. The two-class problems NC vs. AD and NC vs. LBD, show encouraging results with total accuracy of 0.97 (0.07) and 0.97 (0.06) respectively. The three-class problem and the two-class problem AD vs. LBD are not equally encouraging but shows higher accuracy than clinical diagnosis with a total accuracy of 0.79 (0.07) and 0.79 (0.15) respectively. Possible explanations may be that the AD- and LBD group are too similar concerning LBP texture analysis and that the LBD group is too small. Most of the texture features calculated for the AD subjects in the NAWM region were significantly correlated with cognition. Together with the positive classification results from the NAWM region this may suggest that the NAWM region is an important area for studying AD. Both cost-sensitive classification and resampling using SMOTE proved useful and improved the results considerably in many of the tests.",accuracy;Alzheimer disease;article;cognition;controlled study;diffuse Lewy body disease;disease classification;human;jackknife test;major clinical study;mental task;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;recall;scoring system;three dimensional imaging;white matter;white matter lesion;Philips Intera;Signa Excite,"Oppedal, K.;Engan, K.;Eftestøl, T.;Beyer, M.;Aarsland, D.",2017,,10.1016/j.bspc.2016.10.007,0,
2122,Classifying dementia using local binary patterns from different regions in magnetic resonance images,"Dementia is an evolving challenge in society, and no disease-modifying treatment exists. Diagnosis can be demanding and MR imaging may aid as a noninvasive method to increase prediction accuracy. We explored the use of 2D local binary pattern (LBP) extracted from FLAIR and T1 MR images of the brain combined with a Random Forest classifier in an attempt to discern patients with Alzheimer's disease (AD), Lewy body dementia (LBD), and normal controls (NC). Analysis was conducted in areas with white matter lesions (WML) and all of white matter (WM). Results from 10-fold nested cross validation are reported as mean accuracy, precision, and recall with standard deviation in brackets. The best result we achieved was in the two-class problem NC versus AD + LBD with total accuracy of 0.98 (0.04). In the three-class problem AD versus LBD versus NC and the two-class problem AD versus LBD, we achieved 0.87 (0.08) and 0.74 (0.16), respectively. The performance using 3DT1 images was notably better than when using FLAIR images. The results from the WM region gave similar results as in the WML region. Our study demonstrates that LBP texture analysis in brain MR images can be successfully used for computer based dementia diagnosis.",,"Oppedal, K.;Eftestol, T.;Engan, K.;Beyer, M. K.;Aarsland, D.",2015,,10.1155/2015/572567,0,
2123,White matter hyperintensities in mild lewy body dementia,"BACKGROUND: The objective of this study was to explore the load of white matter hyperintensities (WMH) in patients with Lewy body dementia (LBD) and compare to Alzheimer's disease (AD) and normal controls (NC). METHODS: Diagnosis of LBD and AD was made according to consensus criteria and cognitive tests were administered. MRI scans for 77 (61 AD and 16 LBD) patients and 37 healthy elderly control subjects were available for analysis. We segmented WMH from FLAIR images using an automatic thresholding technique and calculated the volume of WMH in several regions of the brain, using non-parametric tests to compare groups. Multivariate regression was applied. RESULTS: There were no significant differences in WMH between AD and LBD. We found a significant correlation between total and frontal WMH and Mini-Mental State Examination (MMSE) and verbal fluency scores in the AD group, but not in the LBD group. CONCLUSION: The WMH load in LBD was similar to that of AD. A correlation between WMH load and cognition was found in the AD group, but not in the LBD group, suggesting that vascular disease contributes to cognitive impairment in AD but not LBD.",,"Oppedal, K.;Aarsland, D.;Firbank, M. J.;Sonnesyn, H.;Tysnes, O. B.;O'Brien, J. T.;Beyer, M. K.",2012,Jan,10.1159/000343480,0,
2124,Heritability of MRI lesion volume in CADASIL: evidence for genetic modifiers,"BACKGROUND AND PURPOSE: The phenotypic expressivity shows striking variability among individuals with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease caused by mutations in NOTCH3. However, little is known about the factors that underlie this variability. We sought to quantify the contribution of modifying genetic effects to individual differences in the volume of cerebral ischemic lesions. METHODS: One hundred and fifty-one affected individuals (mean age+/-SD=45.7+/-10.4) from 95 unrelated families with CADASIL underwent MRI. The volume of lesions visible on T2-weighted images and the intracranial volume (ICV) were quantified and vascular risk factors were assessed. Because of a skewed distribution, lesion volume measures were square-root transformed. Variance component methods were used to estimate the heritability of lesion volumes (ie, the proportion of variation caused by additive genetic factors) after adjusting for covariates. RESULTS: In multivariate analyses, higher age, a larger ICV, and a higher diastolic blood pressure were independently associated with a larger volume of T2-visible lesions (all P<0.05). After adjustment for age the point estimate for the heritability of the square-root-transformed measure of T2 lesion volume was 0.634 (SE=+/-0.286). Adjustment for age, sex, ICV, and diastolic blood pressure increased the estimated heritability to 0.738 (SE+/-0.255). CONCLUSIONS: Heritability estimates in CADASIL suggest a strong modifying influence of genetic factors distinct from the causative NOTCH3 mutation on the amount of ischemic brain lesions. These findings justify a systematic search for genetic variants that modify disease progression.","Adult;Brain/pathology;CADASIL/epidemiology/ genetics/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Quantitative Trait, Heritable;Receptors, Notch/genetics","Opherk, C.;Peters, N.;Holtmannspotter, M.;Gschwendtner, A.;Muller-Myhsok, B.;Dichgans, M.",2006,Nov,10.1161/01.str.0000245084.35575.66,0,
2125,Genome-wide genotyping demonstrates a polygenic risk score associated with white matter hyperintensity volume in CADASIL,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) on MRI are a quantitative marker for sporadic cerebral small vessel disease and are highly heritable. To date, large-scale genetic studies have identified only a single locus influencing WMH burden. This might in part relate to biological heterogeneity of sporadic WMH. The current study searched for genetic modifiers of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease. METHODS: We performed a genome-wide association study to identify quantitative trait loci for WMH volume by combining data from 517 CADASIL patients collected through 7 centers across Europe. WMH volumes were centrally analyzed and quantified on fluid attenuated inversion recovery images. Genotyping was performed using the Affymetrix 6.0 platform. Individuals were assigned to 2 distinct genetic clusters (cluster 1 and cluster 2) based on their genetic background. RESULTS: Four hundred sixty-six patients entered the final genome-wide association study analysis. The phenotypic variance of WMH burden in CADASIL explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21), suggesting a substantial genetic contribution. Using cluster 1 as derivation and cluster 2 as a validation sample, a polygenic score was significantly associated with WMH burden (P=0.001) after correction for age, sex, and vascular risk factors. No single nucleotide polymorphism reached genome-wide significance. CONCLUSIONS: We found a polygenic score to be associated with WMH volume in CADASIL subjects. Our findings suggest that multiple variants with small effects influence WMH burden in CADASIL. The identification of these variants and the biological pathways involved will provide insights into the pathophysiology of white matter disease in CADASIL and possibly small vessel disease in general.","Adult;Aged;CADASIL/epidemiology/ genetics/pathology;Female;Genetic Predisposition to Disease/epidemiology/ genetics;Genome-Wide Association Study;Humans;Hypertension/epidemiology/genetics/pathology;Leukoencephalopathies/epidemiology/ genetics/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Models, Genetic;Quantitative Trait Loci;Risk Factors","Opherk, C.;Gonik, M.;Duering, M.;Malik, R.;Jouvent, E.;Herve, D.;Adib-Samii, P.;Bevan, S.;Pianese, L.;Silvestri, S.;Dotti, M. T.;De Stefano, N.;Liem, M.;Boon, E. M.;Pescini, F.;Pachai, C.;Bracoud, L.;Muller-Myhsok, B.;Meitinger, T.;Rost, N.;Pantoni, L.;Lesnik Oberstein, S.;Federico, A.;Ragno, M.;Markus, H. S.;Tournier-Lasserve, E.;Rosand, J.;Chabriat, H.;Dichgans, M.",2014,Apr,10.1161/strokeaha.113.004461,0,
2126,Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology,"Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability.",,"Opfer, R.;Suppa, P.;Kepp, T.;Spies, L.;Schippling, S.;Huppertz, H. J.",2016,May,10.1016/j.mri.2015.12.031,0,
2127,Pain intensity and pain affect in relation to white matter changes,"Since aging is a risk factor for both dementia and the occurrence of painful conditions, with the number of aged people increasing in the next decades, an increase in the number of elderly people suffering from both conditions can be anticipated. Reliable pain assessment in this population is restricted by reduced communicative and cognitive capacity, with serious consequences for effective pain treatment. White matter changes are frequently observed in the various subtypes of dementia as well as in normal aging, and may play a crucial role in pain processing. In healthy elderly people, reliable pain assessment can be accomplished, which enables examining the relationship between pain experience and white matter changes. A normal structure and function of the white matter is extremely important for dorsolateral prefrontal cortex (DLPFC) functioning, which has recently been linked to pain inhibition. The present study focused on the relation between white matter changes and both pain intensity and pain affect in elderly people without dementia. The Coloured Analogue Scale (CAS) and the Number of Words Chosen-Affective (NWC-A) were applied to measure pain intensity and pain affect, respectively. The presence of white matter changes was significantly related to a higher score on the NWC-A but not the CAS score. These results suggest that pain experience may change as a result of aging and that white matter changes might be indicative for these alterations.","*Affect;Aged;Aged, 80 and over;Aging/*pathology/*psychology;Brain/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Pain/*pathology/*psychology;Pain Measurement;Severity of Illness Index;Statistics as Topic","Oosterman, J. M.;van Harten, B.;Weinstein, H. C.;Scheltens, P.;Scherder, E. J.",2006,Nov,10.1016/j.pain.2006.04.030,0,
2128,Medial temporal lobe atrophy relates to executive dysfunction in Alzheimer's disease,"BACKGROUND: White matter hyperintensities (WMH) have frequently been associated with lower executive function performance. Little is known, however, about the effects of hippocampal atrophy on executive control in Alzheimer's disease (AD). The present study focused on the association of hippocampal atrophy with executive function in AD patients and examined whether a threshold effect is present, indicating that a certain amount of brain damage must be present before cognitive function becomes impaired. Finally, we examined the combined effect of hippocampal atrophy and WMH on cognitive task performance. METHODS: We retrospectively collected neuropsychological and neuroimaging data of 94 AD patients. These patients completed tasks of general cognitive function, executive function, memory, and processing speed. With magnetic resonance imaging (MRI), hippocampal atrophy was rated as medial temporal lobe atrophy (MTA) and cerebrovascular disease was rated as WMH using validated visual rating scales. RESULTS: Medial temporal lobe atrophy (MTA) was associated with lower executive function, general cognitive function, and episodic memory performance. A threshold effect was present, indicating that severe to very severe, but not moderate, MTA was associated with lower executive function. WMH were significantly associated with a single executive test only, whereas the interaction between WMH and MTA was not significantly related to any of the cognitive tasks. CONCLUSIONS: Our findings suggest that AD neuropathology in itself may be responsible for executive dysfunction. Potential explanations for these findings are discussed, focusing on the role of the hippocampus in executive function tests and reduced frontal-posterior connectivity in this patient sample.","Aged;Alzheimer Disease/pathology/ psychology;Atrophy;Educational Status;Executive Function;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Memory, Episodic;Neuroimaging;Neuropsychological Tests;Retrospective Studies;Temporal Lobe/ pathology","Oosterman, J. M.;Oosterveld, S.;Rikkert, M. G.;Claassen, J. A.;Kessels, R. P.",2012,Sep,10.1017/s1041610212000506,0,
2129,What is cerebral small vessel disease?,"An accumulating amount of evidence suggests that the white matter hyperintensities on T(2) weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease.",,"Onodera, O.",2011,June,,0,
2130,Meningitis carcinomatosa with dementia-like symptoms as initial presentation mimicking cerebral infarction,"A 73-year-old man was admitted to our hospital with sore throat, bloody sputum and an abnormal shadow on chest radiograph. He was diagnosed with advanced adenocarcinoma of the lung and received combination chemotherapy consisting of carboplatin and paclitaxel. During the second cycle of chemotherapy, he noted dementia-like symptoms including rapidly progressive disturbance of memorization. Computed tomography scans showed multiple low-density areas without enhancement in the right frontal and temporal lobe, radiate corona and left frontal lobe, which are frequently observed in patients with cerebral infarction. However, enhanced magnetic resonance imaging suggested meningitis carcinomatosa, which was cytologically confirmed by examination of the cerebrospinal fluid. Dementia-like symptoms mimicking cerebral infarction are rarely seen as initial presentation of meningitis carcinomatosa.",,"Onoda, T.;Hiraki, A.;Fujiwara, K.;Aoe, K.;Maeda, T.;Uno, M.;Yamashita, H.;Kohara, H.;Hashimoto, K.;Sakae, K.;Takeyama, H.",2005,2005,,0,
2131,Retinal neurodegeneration on optical coherence tomography and cerebral atrophy,"Neurodegeneration in dementia is mainly evaluated by assessing cerebral atrophy, while retinal neurodegeneration can be quantified in vivo using optical coherence tomography (OCT). We examined the association of retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thinning with global and regional cerebral atrophy on magnetic resonance imaging (MRI). Malay participants aged 60-80 years from the Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial MRI. RNFL and GC-IPL thicknesses were obtained from spectral domain-OCT; and cerebral grey and white matter volumes were obtained from MRI scans using a validated segmentation tool. Linear regression models were constructed with adjustment for age and sex; and additionally for vascular risk factors and MRI markers including intracranial volume. 164 participants without glaucoma with gradable quality MRI and OCT scans were included for analysis. GC-IPL thinning was associated with reduction in total brain volume in the occipital (mean change in GC-IPL per standard deviation (SD) decrease in occipital lobe volume: -1.77 mum, 95% confidence interval (CI) -6.55 to 0.01 mum) and temporal lobes (mean change in GC-IPL per SD decrease in temporal lobe volume: -3.45 mum, 95%CI -5.40 to -1.49 mum) in multivariate adjusted models. In particular, GC-IPL thinning was primarily associated with grey matter volume, whereas no association was found with white matter changes. Retinal neuronal damage, as reflected by GC-IPL thinning, was independently associated with grey matter loss in the occipital and temporal lobes, suggesting that retinal OCT may provide insights for assessing neurodegeneration in the brain.","Adult;Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Female;Gray Matter/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/ pathology;Nerve Fibers/pathology;Retina/ pathology;Retinal Ganglion Cells/pathology;Tomography, Optical Coherence;White Matter/pathology","Ong, Y. T.;Hilal, S.;Cheung, C. Y.;Venketasubramanian, N.;Niessen, W. J.;Vrooman, H.;Anuar, A. R.;Chew, M.;Chen, C.;Wong, T. Y.;Ikram, M. K.",2015,Jan 1,10.1016/j.neulet.2014.10.010,0,
2132,Influence of diabetes mellitus on longitudinal atrophy and cognition in Parkinson's disease,"OBJECTIVE: To investigate the impact of diabetes mellitus (DM) on cognitive performance and longitudinal volumetric brain changes in a cohort of cognitively normal mild PD patients. METHODS: Prospective study of idiopathic PD subjects who underwent baseline and follow-up MRI imaging and neuropsychological assessments at 6month intervals for 3years. Subjects were classified based on the presence (PD-DM) or absence of DM (PD-No DM) at baseline. Volumetric analysis was performed using FreeSurfer 5.3 image analysis suite. Brain volume and cognition were compared and analyzed cross-sectionally and longitudinally. Analyses were corrected for intracranial volume. RESULTS: There were 65 PD-no DM and 12 PD-DM subjects at baseline with comparable global cognition at baseline. PD-DM subjects had lower cortical grey matter (GM), amygdala, frontal white matter and temporal white matter volumes and higher total white matter hyperintensity and periventricular hyperintensities. After mean follow-up of 29.08months, there were 51 PD-no DM and 11 PD-DM subjects. PD-DM subjects demonstrated greater decline in MMSE and MOCA scores compared to PD-No DM. PD-DM subjects had a higher rate of atrophy in the cortical WM, particularly in the parietal and occipital white matter. CONCLUSION: Mild PD patients with DM have lower GM and WM volumes at baseline and higher WMH volumes, despite comparable cognitive scores. Longitudinally, DM in PD results in greater rate of cognitive decline, associated with higher WM atrophy.",Diabetes mellitus;Mild cognitive impairment;Parkinson's disease;Parkinson's disease with dementia,"Ong, M.;Foo, H.;Chander, R. J.;Wen, M. C.;Au, W. L.;Sitoh, Y. Y.;Tan, L.;Kandiah, N.",2017,Jun 15,,0,
2133,Automatic white matter lesion segmentation using an adaptive outlier detection method,White matter (WM) lesions are diffuse WM abnormalities that appear as hyperintense (bright) regions in cranial magnetic resonance imaging (MRI).,,"Ong, K. H.;Ramachandram, D.;Mandava, R.;Shuaib, I. L.",2012,July,,0,
2134,Delayed neurotoxicity in primary central nervous system lymphoma,"BACKGROUND: Treatment for primary central nervous lymphoma (PCNSL) with chemotherapy and radiotherapy has resulted in improved survival, but some patients develop neurologic deterioration that represents a treatment-related toxic effect. This delayed neurotoxicity has been poorly defined in the literature, and the underlying mechanisms are unknown. OBJECTIVE: To describe the clinical findings, time course, and pathophysiologic mechanisms associated with neurotoxicity in an attempt to generate hypotheses for future studies that address prevention and treatment of this complication of successful PCNSL therapy. DESIGN: Retrospective review. SETTING: Department of Neurology, Memorial Sloan-Kettering Cancer Center. PATIENTS: One hundred eighty-five patients treated for PCNSL, including 43 who developed neurotoxicity. MAIN OUTCOME MEASURES: Potential risk factors, clinical course, and neuropsychological, neuroimaging, and histologic findings. RESULTS: The 5-year cumulative incidence of neurotoxicity was 24%; this incidence increases over time. Neurotoxicity presented as a rapidly progressive subcortical dementia characterized by psychomotor slowing, executive and memory dysfunction, behavioral changes, gait ataxia, and incontinence. Imaging findings revealed diffuse white matter disease and cortical-subcortical atrophy. Available autopsy data showed white matter damage with gliosis, thickening of small vessels, and demyelination. Statistical analyses were performed, accounting for death as a competing risk. Older age (P = .01), mental status changes at diagnosis (P = .04), female sex (P = .05), and radiotherapy (P<.001) predicted neurotoxicity on univariate analysis, but only radiotherapy remained significant in the multivariate setting. CONCLUSION: These findings suggest that the core pathophysiologic mechanism is the interruption of frontal-subcortical circuits mediated by radiation damage, possibly caused by progressive microvascular alterations, loss of oligodendrocyte progenitors, or oxidative stress.",Age Factors;Antineoplastic Combined Chemotherapy Protocols/adverse effects;Brain/drug effects/pathology/ radiation effects;Brain Diseases/epidemiology/ etiology/therapy;Central Nervous System Neoplasms/ therapy;Cognition Disorders/etiology/pathology/physiopathology;Combined Modality Therapy;Female;Humans;Lymphoma/ therapy;Male;Middle Aged;Neurotoxicity Syndromes/epidemiology/ etiology/physiopathology;Radiotherapy/ adverse effects;Retrospective Studies;Risk Factors;Sex Factors;Time Factors,"Omuro, A. M.;Ben-Porat, L. S.;Panageas, K. S.;Kim, A. K.;Correa, D. D.;Yahalom, J.;Deangelis, L. M.;Abrey, L. E.",2005,Oct,10.1001/archneur.62.10.1595,0,
2135,"White Matter Lesion Assessment in Patients with Cognitive Impairment and Healthy Controls: Reliability Comparisons between Visual Rating, a Manual, and an Automatic Volumetrical MRI Method-The Gothenburg MCI Study","Age-related white matter lesions (WML) are a risk factor for stroke, cognitive decline, and dementia. Different requirements are imposed on methods for the assessment of WML in clinical settings and for research purposes, but reliability analysis is of major importance. In this study, WML assessment with three different methods was evaluated. In the Gothenburg mild cognitive impairment study, MRI scans from 152 participants were used to assess WML with the Fazekas visual rating scale on T2 images, a manual volumetric method on FLAIR images, and FreeSurfer volumetry on T1 images. Reliability was acceptable for all three methods. For low WML volumes (2/3 of the patients), reliability was overall lower and nonsignificant for the manual volumetric method. Unreliability in the assessment of patients with low WML with manual volumetry may mainly be due to intensity variation in the FLAIR sequence used; hence, intensity standardization and normalization methods must be used for more accurate assessments. The FreeSurfer segmentations resulted in smaller WML volumes than the volumes acquired with the manual method and showed deviations from visible hypointensities in the T1 images, which quite likely reduces validity.",,"Olsson, E.;Klasson, N.;Berge, J.;Eckerstrom, C.;Edman, A.;Malmgren, H.;Wallin, A.",2013,,10.1155/2013/198471,0,
2136,MR detection of white matter disease of the brain in patients with HIV infection: fast spin-echo vs conventional spin-echo pulse sequences,"OBJECTIVE: Although fast spin-echo images and slower spin-echo images have similar contrast characteristics, the two techniques have not yet been shown to be equivalent in all aspects of brain imaging. To determine if the two sequences are equivalent, we compared detection of white matter lesions, image quality, and artifact degradation on fast spin-echo and spin-echo proton density-weighted and T2-weighted MR images of the brain in prospectively selected patients who were seropositive for HIV. SUBJECTS AND METHODS: Fast spin-echo and spin-echo MR images of the brain were obtained in 153 consecutive subjects. The images were reviewed independently by three experienced neuroradiologists. The size, number, and location of white matter lesions were compared for the two techniques. Image quality, motion artifact, CSF flow artifact, and gray-white matter differentiation were graded on a five-point scale. RESULTS: No statistical difference was found in gray-white matter differentiation. Overall image quality, CSF flow artifacts, and motion artifacts were slightly worse on the fast spin-echo images (p < .05). Although some variability existed in the detection of lesions less than 5 mm in diameter, the differences was small, and all larger lesions were detected by both techniques. Agreement between fast spin-echo and conventional spin-echo techniques was nearly exact with respect to characterizing findings in brain as either normal or abnormal. CONCLUSIONS: Fast spin-echo and spin-echo MR of the brain produce images of similar quality and show white matter lesions equally well. These results support the replacement of slower, conventional spin-echo pulse sequences with faster fast spin-echo sequences.",AIDS Dementia Complex/ diagnosis/epidemiology;Adult;Artifacts;Brain/ pathology;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Prospective Studies,"Olson, E. M.;Healy, J. F.;Wong, W. H.;Youmans, D. C.;Hesselink, J. R.",1994,May,10.2214/ajr.162.5.8166010,0,
2137,White matter disease in AIDS: findings at MR imaging,"A review of the magnetic resonance (MR) images of 365 patients with acquired immunodeficiency syndrome (AIDS) revealed that 112 (31%) had signal abnormalities confined to the white matter. Four patterns were observed: (a) diffuse: widespread involvement of a large area; (b) patchy: localized involvement with ill-defined margins; (c) focal: well-defined areas of involvement; and (d) punctate: small foci less than 1 cm in diameter. Clinical or pathologic findings were available in 60 of the 112 patients and were correlated with the white matter patterns seen on MR images. The diffuse pattern correlated with AIDS dementia complex (ADC), which was the most common clinical diagnosis. Patchy or punctate lesions may be seen with ADC but are less common. Focal white matter lesions were not seen in patients with ADC but were seen in all six patients with progressive multifocal leukoencephalopathy, in both patients with lymphoma, and in one patient with toxoplasmosis. The authors conclude that white matter lesions are are common in AIDS and are often secondary to direct infection of the brain with human immunodeficiency virus, which causes the ADC and usually produces a diffuse white matter pattern. Biopsy is probably not indicated in these patients. Focal white matter lesions suggest a focal infection or tumor, and biopsy may be warranted.",Acquired Immunodeficiency Syndrome/ complications;Adult;Aged;Brain/ pathology;Brain Diseases/diagnosis/ etiology;Dementia/diagnosis/ etiology;Humans;Magnetic Resonance Imaging;Middle Aged,"Olsen, W. L.;Longo, F. M.;Mills, C. M.;Norman, D.",1988,Nov,10.1148/radiology.169.2.3174991,0,
2138,Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis,"We investigated whether older adults without subjective memory complaints, but who present with cognitive decline in the laboratory, demonstrate atrophy in medial temporal lobe (MTL) subregions associated with Alzheimer's disease. Forty community-dwelling older adults were categorized based on Montreal Cognitive Assessment (MoCA) performance. Total gray/white matter, cerebrospinal fluid, and white matter hyperintensity load were quantified from whole-brain T1-weighted and fluid-attenuated inversion recovery magnetic resonance imaging scans, whereas hippocampal subfields and MTL cortical subregion volumes (CA1, dentate gyrus/CA2/3, subiculum, anterolateral and posteromedial entorhinal, perirhinal, and parahippocampal cortices) were quantified using high-resolution T2-weighted scans. Cognitive status was evaluated using standard neuropsychological assessments. No significant differences were found in the whole-brain measures. However, MTL volumetry revealed that anterolateral entorhinal cortex (alERC) volume-the same region in which Alzheimer's pathology originates-was strongly associated with MoCA performance. This is the first study to demonstrate that alERC volume is related to cognitive decline in undiagnosed community-dwelling older adults.","Aged;Aged, 80 and over;Aging/ pathology/ psychology;Alzheimer Disease/diagnosis/etiology/pathology;Cognition/ physiology;Cognitive Dysfunction/diagnosis/ etiology/ pathology;Diffusion Magnetic Resonance Imaging;Entorhinal Cortex/diagnostic imaging/ pathology;Female;Humans;Male;Middle Aged;Organ Size;Aging;Dementia;Hippocampus;Memory;Mild cognitive impairment;Neuroimaging","Olsen, R. K.;Yeung, L. K.;Noly-Gandon, A.;D'Angelo, M. C.;Kacollja, A.;Smith, V. M.;Ryan, J. D.;Barense, M. D.",2017,Sep,,0,
2139,The effect of lifelong bilingualism on regional grey and white matter volume,"Lifelong bilingualism is associated with the delayed diagnosis of dementia, suggesting bilingual experience is relevant to brain health in aging. While the effects of bilingualism on cognitive functions across the lifespan are well documented, less is known about the neural substrates underlying differential behaviour. It is clear that bilingualism affects brain regions that mediate language abilities and that these regions are at least partially overlapping with those that exhibit age-related decline. Moreover, the behavioural advantages observed in bilingualism are generally found in executive function performance, suggesting that the frontal lobes may also be sensitive to bilingualism, which exhibit volume reductions with age. The current study investigated structural differences in the brain of lifelong bilingual older adults (n=14, mean age=70.4) compared with older monolinguals (n=14, mean age=70.6). We employed two analytic approaches: 1) we examined global differences in grey and white matter volumes; and, 2) we examined local differences in volume and cortical thickness of specific regions of interest previously implicated in bilingual/monolingual comparisons (temporal pole) or in aging (entorhinal cortex and hippocampus). We expected bilinguals would exhibit greater volume of the frontal lobe and temporal lobe (grey and white matter), given the importance of these regions in executive and language functions, respectively. We further hypothesized that regions in the medial temporal lobe, which demonstrate early changes in aging and exhibit neural pathology in dementia, would be more preserved in the bilingual group. As predicted, bilinguals exhibit greater frontal lobe white matter compared with monolinguals. Moreover, increasing age was related to decreasing temporal pole cortical thickness in the monolingual group, but no such relationship was observed for bilinguals. Finally, Stroop task performance was positively correlated with frontal lobe white matter, emphasizing the importance of preserved white matter in maintaining executive function in aging. These results underscore previous findings implicating an association between bilingualism and preserved frontal and temporal lobe function in aging. This article is part of a Special Issue entitled SI: Memory A.","Age Factors;Aged;Aging/*psychology;Analysis of Variance;Cerebral Cortex/anatomy & histology/*physiology;Female;Gray Matter/*anatomy & histology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;*Multilingualism;Neuropsychological Tests;White Matter/*anatomy & histology;Aging;Bilingual;Cognitive reserve;Hippocampus;Mri;Volumetric","Olsen, R. K.;Pangelinan, M. M.;Bogulski, C.;Chakravarty, M. M.;Luk, G.;Grady, C. L.;Bialystok, E.",2015,Jul 1,10.1016/j.brainres.2015.02.034,0,
2140,Senile dementia of the Binswanger's type,"Senile dementia of the Binswanger's type is a term used to describe a dementia syndrome characterized by onset in the sixth or seventh decade of life, subcortical neurologic deficits, psychiatric disorders and evidence of hypertension or systemic vascular disease. The status of senile dementia of the Binswanger's type as a distinct entity is a matter of some controversy. The array of neuroimaging abnormalities and clinical findings attributed to this condition overlap with a number of other neuropathologies. Leukoaraiosis, or attenuation of subcortical white matter, seen on computed tomographic scans or magnetic resonance imaging of the brain, is a hallmark of senile dementia of the Binswanger's type. The clinical findings associated with Binswanger's disease are varied but typically include a progressive dementia, depression and 'subcortical' dysfunction such as gait abnormalities, rigidity and neurogenic bladder. Treatment is largely supportive and includes a discussion about advanced directives, social support and antidepressant therapy. Control of hypertension and aspirin prophylaxis may help prevent further progression of white matter disease.",,"Olsen, C. G.;Clasen, M. E.",1998,December,,0,
2141,A novel mutation in the Notch3 gene in an italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Genetic and magnetic resonance spectroscopic findings,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary syndrome caused by mutations of the Notch3 gene, usually localized to exons 3 and 4. Objectives: To report a novel pathogenetic mutation occurring in exon 6 of the Notch3 gene, a location not previously recognized in patients with CADASIL, and to report the results of magnetic resonance spectroscopy in CADASIL. Methods: Mutation analysis of the Notch3 gene was performed in 2 patients belonging to a large kindred manifesting CADASIL, as well as in 7 clinically unaffected members of the family and 200 control chromosomes. Proton magnetic resonance spectroscopy was used to estimate metabolite resonance intensities in the 2 affected subjects. Results: Sequence analysis of the Notch3 gene showed a new missense mutation CGC→TGC in codon 332 of exon 6, resulting in the replacement of an arginine residue with a cysteine. This mutation was never observed in the 7 unaffected members of the family and the 200 control chromosomes examined. Proton magnetic resonance spectroscopy showed a diffuse decrease in cerebral N-acetylaspartate, indicating the presence of wide-spread axonal damage. Conclusions: Our findings emphasize the role of direct DNA sequence analysis for the diagnosis of CADASIL. Moreover, the results of proton magnetic resonance spectroscopy suggest that widespread axonal damage may be an early finding of the disease.",DNA;adult;article;autosomal dominant disorder;brain infarction;CADASIL;case report;cerebrovascular disease;gene mutation;human;male;missense mutation;nuclear magnetic resonance imaging;pedigree analysis;polymerase chain reaction;priority journal;proton nuclear magnetic resonance;syndrome delineation;Philips Gyroscan NT,"Oliveri, R. L.;Muglia, M.;De Stefano, N.;Mazzei, R.;Labate, A.;Conforti, F. L.;Patitucci, A.;Gabriele, A. L.;Tagarelli, G.;Magariello, A.;Zappia, M.;Gambardella, A.;Federico, A.;Quattrone, A.",2001,,,0,
2142,Chagas disease is independently associated with brain atrophy,"Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain involvement in CD has been attributed to left ventricular dysfunction, resulting in chronic brain ischemia due to hypoperfusion and/or embolic infarcts. However, cognitive impairment in CD may occur independently of cardiac disease. Therefore, we aimed to investigate head computed tomography (CT) findings in patients with Chagas disease cardiomyopathy (CDC) in comparison with other cardiomyopathies (OC). We studied 73 patients with CDC (n = 41) or OC (n = 32) matched for age and gender. These patients underwent head CT, rated by an investigator blinded to all clinical information. Head CT was rated for the presence of lacunar or territorial infarcts, as well as for measuring the total volumes of the brain, cerebellum and ventricles. Total brain volume was smaller in CDC as compared to OC patients (1,135 ± 150 vs. 1,332 ± 198 cm3, P < 0.001). Cerebellar and ventricular volumes did not differ between the groups. The prevalence of brain infarcts did not differ significantly between the groups. Chagas disease was the only independent predictor of brain atrophy in the multivariable analysis (OR = 1.38; 95% CI = 1.06-1.79, P = 0.017). Chagas disease is associated with brain atrophy independent of structural cardiac disease related to cardiomyopathy. Brain atrophy, rather than multiple infarcts, may represent the main anatomical substrate of cognitive impairment in Chagas disease. © 2009 Springer-Verlag.",adult;article;brain atrophy;brain infarction;brain size;brain ventricle;cardiomyopathy;cerebellum;Chagas disease;computer assisted tomography;controlled study;diastole;disease association;disease duration;female;heart ejection fraction;heart left ventricle contraction;human;major clinical study;male;priority journal,"Oliveira-Filho, J.;Vieira-De-Melo, R. M.;Reis, P. S. O.;Lacerda, A. M.;Neville, I. S.;Cincura, C.;Menezes, D. F.;Viana, L. C.;Jesus, P. A. P.;Lopes, A. A.;Reis, F. J. F. B.;Furie, K. L.",2009,,,0,
2143,Binswanger's subcortical arteriosclerotic encephalopathy: a special form of dementia associated with systemic arterial hypertension,"The encephalopathy is characterized by an important arteriosclerotic involvement of the vessels of the cerebral white matter and a diffuse subcortical demyelination, sparing the cortex. The diagnosis is presently possible, ante mortem, by connecting the clinical picture with the CT scan findings, which are essential. Three cases with Binswanger encephalopathy are reported and the following picture was found: age 50 to 70 years old at the onset; dementia with scanty neurological signs; systemic arterial hypertension; subacute course of the disease; and a CT scan, highly characteristic, that shows bilateral and symmetric subcortical hypodensity. In one of the patients, that eventually died, an angiography disclosed a right internal carotid thrombosis and a diminished flow in the thalamic striate arteries in both sides. The other two patients are apparently stabilized with anti-hypertensive medication. Binswanger encephalopathy is still seldom described in spite of being a very well defined entity. This diagnosis should be considered much more frequently because it is possible to prevent the encephalopathy avoiding systemic hypertension that is probably intimately linked with the genesis of the disease.",aged;article;brain atherosclerosis;case report;computer assisted tomography;dementia;electroencephalography;human;hypertension;male;middle aged;pathophysiology;radiography;syndrome,"Oliveira, A. S.;Massaro, A. R.;De Campos, C. J.;Zukerman, E.",1986,,,0,
2144,Clinical Predictors of Stroke Mimics in Patients Treated with Recombinant Tissue Plasminogen Activator according to a Normal Multimodal Computed Tomography Imaging,"BACKGROUND: Multimodal computed tomography imaging (MCTI) is increasingly used for rapid assessment of acute stroke. We investigated characteristics and final diagnoses of patients treated with recombinant tissue plasminogen activator (rt-PA) while admission imaging was unremarkable. METHODS: From our prospectively collected stroke database (2013-2016), we identified consecutive patients treated with rt-PA on the basis of an unremarkable brain MCTI and assessed with a 24-hour follow-up brain magnetic resonance imaging (MRI). Demographic data, medical history, score on the 15-item National Institute of Health Stroke Scale, and final diagnosis were considered. Absence of MRI infarction and alternate diagnosis defined stroke mimics (SMs). Univariable and multivariable logistic regression analyses identified factors predictive of SMs. RESULTS: Sixty-eight (47.9%) SMs, 63 (44.4%) strokes, and 11 (7.7%) aborted strokes were found. SMs had more often aphasia (P = .003) and hemianopia (P = .0008), whereas upper limb weakness (ULW) (P = .03) and limb ataxia (P = .002) were more prevalent in strokes. Headache (adjusted odds ratio [Adj. OR], 3.89 [95% confidence interval {CI} 1.44-10.47]), relevant history of epilepsy, migraine, dementia or depression (Adj. OR 3.66 [95% CI 1.31-10.18]), unilateral sensory loss (Adj. OR 2.60 [95% CI 1.05-6.45]), and hemianopia (Adj. OR 4.94 [95% CI 1.46-16.77]) were independent predictors of SMs whereas ULW (Adj. OR 3.16 [95% CI 1.28-7.82]) and ataxia (Adj. OR 3.81 [95% CI 1.43-10.13]) predicted stroke. Sensitivity of hemianopia or aphasia for SMs was 52.9%, with specificity of 84.1%, positive predictive value of 78.3%, and negative predictive value of 62.4%. CONCLUSIONS: Hemianopia and/or aphasia with normal MCTI suggest SMs. Diffusion-weighted MRI might be discussed before rt-PA administration in patients with such a clinical pattern.",Stroke mimics;multimodal CT imaging;safety;thrombolysis,"Olindo, S.;Chardonnet, M.;Renou, P.;Coignion, C.;Debruxelles, S.;Poli, M.;Sagnier, S.;Rouanet, F.;Sibon, I.",2018,Feb,,0,
2145,Temporal lobe atrophy and white matter lesions are related to major depression over 5 years in the elderly,"The influence of organic brain changes on the development of depression in the elderly is uncertain. Cross-sectional studies, most often from clinical samples, report associations with brain atrophy and cerebrovascular disease, while longitudinal population studies have given mixed results. Our aim was to investigate whether cortical atrophy and white matter lesions (WMLs) on computed tomography (CT) predict occurrence of depression in the elderly. This is a prospective population-based study with 5-year follow-up. The baseline sample included 525 elderly subjects, aged 70-86 years, without dementia or major depression, with a score on the Mini-Mental State Examination above 25, and without dementia at follow-up. Cortical atrophy and WMLs were evaluated at baseline using CT. The main outcome measure was development of major or minor depression at follow-up according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, as evaluated using neuropsychiatric examinations and hospital discharge registers. Logistic regression was used to estimate risk. Over the period of 5 years, 20 individuals developed major and 63 minor depression. Presence of temporal lobe atrophy (odds ratio (O=R)2.81, 95% confidence interval (CI) 1.04-7.62) and moderate-to-severe WMLs (OR3.21, 95% CI 1.00-10.26) independently predicted major, but not minor, depression after controlling for various confounders. Other brain changes did not predict occurrence of depression. Our findings suggest that temporal lobe atrophy and WMLs represent relatively independent and complementary pathways to major depression in the elderly. This may have implications for prevention, as both neurodegeneration and cerebrovascular disease have been related to preventable factors. © 2010 Nature Publishing Group All rights reserved.",aged;article;brain atrophy;brain damage;computer assisted tomography;dementia;Diagnostic and Statistical Manual of Mental Disorders;female;follow up;human;major clinical study;major depression;male;Mini Mental State Examination;outcome assessment;population research;priority journal;temporal lobe;white matter lesion,"Olesen, P. J.;Gustafson, D. R.;Simoni, M.;Pantoni, L.;Stling, S.;Guo, X.;Skoog, I.",2010,,,0,
2146,Pattern of and risk factors for brain microbleeds in neurodegenerative dementia,"Objective: A cross-sectional study was conducted to describe the prevalence, locations, and risk factors for brain microbleeds (BMBs) in neurodegenerative dementia. Methods: The database of the Alzheimer Center Reina Sofia Foundation was searched, BMBs were described, and the potential associations of BMBs were investigated using univariate statistics. Results: A total of 148 patients (age 81.6 [standard deviation 6.7], 79.1% female) were studied. Prevalence of BMBs was 44.6%. A group of patients with unusually high (ie,≥4) number of BMBs were identified, which displayed higher number of vascular risk factors and vascular diseases. Brain microbleeds were also associated with ischemic lesions in the basal ganglia (r =.39), clinical diagnosis of Alzheimer's disease (AD) and cerebrovascular disease (r =.33), cortical infarction (r = .20), and antiaggregant or anticoagulant treatment duration (r =.20). Conclusions: Brain microbleeds are associated with vascular burden and AD diagnosis in old patients with neurodegenerative dementia. More research is warranted regarding the mechanisms and potential clinical implications of these results. © The Author(s) 2013.",aged;aging;Alzheimer disease;anticoagulant therapy;article;basal ganglion;brain hemorrhage;brain infarction;brain microbleed;cerebrovascular disease;cross-sectional study;dementia;diabetes mellitus;dyslipidemia;female;atrial fibrillation;human;hypertension;ischemic heart disease;major clinical study;male;prevalence;risk factor;tobacco use;treatment duration;vascular disease,"Olazarán, J.;Ramos, A.;Boyano, I.;Alfayate, E.;Valentí, M.;Rábano, A.;Álvarez-Linera, J.",2014,,,0,
2147,Clinical and anatomical correlates of gait dysfunction in Alzheimer's disease,"We conducted a cross-sectional study to investigate the clinical and anatomical correlates of gait dysfunction in advanced Alzheimer's disease (AD). A comprehensive clinical protocol that included cognitive, functional, behavioral, and motor variables was administered to patients with probable AD (n = 100), possible AD (n = 17), and AD with cerebrovascular disease (AD + CVD) (n = 27). Gait dysfunction was evaluated with the Rating Scale for Gait Evaluation in Cognitive Deterioration and magnetic resonance imaging was analyzed in 94 patients (volumetry study) and 78 patients (diffusion tensor imaging study). Univariate correlations, multivariate regression, and statistical parametric mapping analyses were conducted in the total sample and in the subsample of patients with probable AD. Mean age was 82.5 (SD 6.3, range 56 to 98), 83.3% were female patients, and 95.1% displayed moderate to severe dementia. Parkinsonism, patient setting (nursing home), dementia severity, apathy, and (worse) cognitive performance significantly predicted gait dysfunction in the total sample (p < 0.05, R(2) = 0.58), whereas parkinsonism, patient setting, and limb weakness due to non-AD conditions predicted gait dysfunction in probable AD (p < 0.05, R(2) = 0.57). Gait dysfunction was related to atrophy in the motor cortex, the middle cingulate, the anterior insula, the right caudate (total sample only), and the anterior lobe of the cerebellum (p < 0.01, corrected). Significant correlations were also observed between gait dysfunction and damage in several white matter locations (p < 0.001, uncorrected). The present results are congruent with a model of multi-system gray matter degeneration, with progressive damage to critical regions (i.e., motor cortex, cingulate, insula, and cerebellum) producing gait dysfunction and, eventually, gait loss in AD.","Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/ pathology/ physiopathology;Atrophy/epidemiology/pathology/physiopathology;Brain/ pathology;Caudate Nucleus/pathology;Cerebellum/pathology;Cerebral Cortex/pathology;Comorbidity;Cross-Sectional Studies;Diffusion Tensor Imaging;Female;Gait/physiology;Gait Disorders, Neurologic/epidemiology/ pathology/ physiopathology;Gyrus Cinguli/pathology;Humans;Inpatients;Male;Middle Aged;Motor Cortex/pathology;Nursing Homes;Outpatients;Parkinsonian Disorders/epidemiology/pathology/physiopathology","Olazaran, J.;Hernandez-Tamames, J. A.;Molina, E.;Garcia-Polo, P.;Dobato, J. L.;Alvarez-Linera, J.;Martinez-Martin, P.",2013,,10.3233/jad-2012-121207,0,
2148,Lymphocytic primary angiitis of the central nervous system with fan-shaped linear enhancement converging to the lateral ventricles: A case report,"We report a case of lymphocytic primary angiitis of the central nervous system (PACNS) with a characteristic gadolinium-enhancement pattern on magnetic resonance imaging (MRI). A 48-year-old, right-handed man presented with a 3-month history of tremor and progressing dementia. Neurologic examination revealed cognitive decline with anterograde amnesia and postural tremor of the fingers. Except for the positive result of serum antinuclear antibody, intense investigations for infectious, rheumatic and neoplastic diseases were negative. Analysis of cerebrospinal fluid showed mild pleocytosis (14 cells/μl). Brain MRI revealed diffuse hyperintense areas in the deep cerebral white matter on T<inf>2</inf>-weighted images. Gadolinium-enhanced T<inf>1</inf>-weighted images demonstrated fan-shaped multiple linear enhancements converging to the body of the lateral ventricles. Brain biopsy showed intense infiltration of small lymphocytes without atypia or granuloma mainly within the vessel walls and perivascular spaces. The diagnosis of lymphocytic PACNS was made. Administration of corticosteroid markedly improved the tremor and cognitive dysfunction. MRI after the treatment showed resolution of the abnormal fan-shaped linear enhancement. He returned to his previous occupation. PACNS should be included in the differential diagnosis for fan-shaped linear enhancement converging to the lateral ventricles on MRI in patients with unexplained progressing dementia.",,"Okunomiya, T.;Kageyama, T.;Tanaka, K.;Kambe, D.;Shinde, A.;Suenaga, T.",2014,2014,,0,
2149,"A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), diagnosed in the age of puberty","We report a 13-year-old boy with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) at an early stage. He showed migraine, cognitive deficits, depressive episodes and areas of white matter hyperintensity on MRI. There were no first-degree relatives accompanied with similar symptoms. T2-and fluid-attenuated inversion recovery (FLAIR) -weighted brain MRI revealed areas of apparently symmetric high intensity in the deep white matter and periventicular caps. On ultrastructural studies of the biopsied skin, there were free granular osmiophilic materials (GOM) between vascular smooth muscle cells in the cutaneous vessels. But there were no excavations in the cell membranes that contained GOM. On immunostaining with Notch3 monoclonal antibodies, granular staining was not observed in vessels of the skin. No mutation was detected on DNA analysis of the Notch3 gene (exon 4 and part of exon 5) in peripheral leukocytes. Although the frequencies of migraine episodes and depressive episodes decreased with amitriptyline and ibuprofen, the cognitive deficits (delayed-recall impairment) and areas of white matter hyperintensity on MRI have been unchanged for the past four years.",amitriptyline;ibuprofen;monoclonal antibody;notch3 monoclonal antibody;Notch3 receptor;protein antibody;unclassified drug;adolescent;article;brain ventricle;CADASIL;case report;cell membrane;clinical feature;cognitive defect;depression;diffusion tensor imaging;DNA determination;exon;family history;gene mutation;human;human cell;human tissue;immunohistochemistry;leukocyte;male;migraine;nuclear magnetic resonance imaging;puberty;skin biopsy;skin blood vessel;smooth muscle fiber;ultrastructure;vascular smooth muscle;white matter,"Okumura, K.;Tsuru, T.;Aizaki, K.;Akikusa, B.",2007,,,0,
2150,A case of dural arteriovenous malformation associated with progressive dementia showing marked improvement with endovascular treatment,"An 81-year-old man was admitted with a 3-month history of progressive dementia. Neurological examination revealed marked dementia, parkinsonism and myoclonus in his extremities. His cerebrospinal fluid examination was normal. An electroencephalogram showed a mildly slowed background. Computed tomography (CT) disclosed diffuse low-density areas in bilateral cerebral white matter. Contrast-enhanced CT demonstrated vermiform enhancement of engorged cortical veins, suggesting increased pressure of the venous system. Magnetic resonance imaging (MRI) disclosed diffuse high-intensity areas in bilateral cerebral white matter on T2-weighted images, and abnormal flow- voids presenting venous congestion on proton-density images. Cerebral angiography revealed arteriovenous malformation (AVM) fed by four branches of the right external carotid artery with retrograde drainage into the right transverse sinus, superior sagittal sinus, and dilated cortical veins. The ipsilateral sigmoid sinus was not visualized. After transarterial embolization, transvenous embolization of the right transverse sinus was performed. These treatments resulted in a marked clinical improvement. We emphasize the role of AVM as a cause of progressive dementia.",,"Okuizumi, K.;Watanabe, K.;Yamazaki, M.;Koike, T.;Onishi, Y.",1998,February,,0,
2151,[Diagnostic imaging techniques in the investigation of dementia] Bildediagnostiske metoder ved demensutredning,"BACKGROUND: Neuroimaging can provide valuable information in the diagnostic work-up of patients presenting with suspected dementia. MATERIAL AND METHODS: Based on our experience from a memory clinic at Ulleval University Hospital in Oslo, Norway and on relevant literature identified on Medline, we give an overview of the use of neuroimaging methods in patients with suspected dementia. RESULTS AND INTERPRETATION: CT of the brain should be offered to all patients with suspected dementia as CT can provide essential diagnostic information regarding focal cerebral pathology (tumour, haemorrhage, normal pressure hydrocephalus). A CT scan is of no value in the diagnostic evaluation of patients with mild to moderate Alzheimer's disease as age-related atrophy may be a confounding factor. CT is necessary to reveal infarcts when vascular dementia is suspected, but lacks sensitivity in the detection of diffuse cerebrovascular disease. MRI is recommended in younger patients and may be used to diagnose subcortical lesions, e.g. leukoariosis. The accuracy of SPECT in the assessment of patients with cognitive impairment is not yet established though it seems to be a promising method for the detection of frontotemporal dementia. Functional MR may play a role in the work-up of dementia in the future.","Alzheimer Disease/ diagnosis/diagnostic imaging;Brain/diagnostic imaging/pathology;Dementia/ diagnosis/diagnostic imaging;Dementia, Vascular/diagnosis/diagnostic imaging;Humans;Magnetic Resonance Imaging;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Oksengard, A. R.;Haakonsen, M.;Dullerud, R.;Babovic, A.;Laake, K.;Engedal, K.",2002,Mar 10,,0,
2152,Diagnostic imaging techniques in the investigation of dementia,"BACKGROUND: Neuroimaging can provide valuable information in the diagnostic work-up of patients presenting with suspected dementia. MATERIAL AND METHODS: Based on our experience from a memory clinic at Ulleval University Hospital in Oslo, Norway and on relevant literature identified on Medline, we give an overview of the use of neuroimaging methods in patients with suspected dementia. RESULTS AND INTERPRETATION: CT of the brain should be offered to all patients with suspected dementia as CT can provide essential diagnostic information regarding focal cerebral pathology (tumour, haemorrhage, normal pressure hydrocephalus). A CT scan is of no value in the diagnostic evaluation of patients with mild to moderate Alzheimer's disease as age-related atrophy may be a confounding factor. CT is necessary to reveal infarcts when vascular dementia is suspected, but lacks sensitivity in the detection of diffuse cerebrovascular disease. MRI is recommended in younger patients and may be used to diagnose subcortical lesions, e.g. leukoariosis. The accuracy of SPECT in the assessment of patients with cognitive impairment is not yet established though it seems to be a promising method for the detection of frontotemporal dementia. Functional MR may play a role in the work-up of dementia in the future.","Alzheimer Disease/ diagnosis/radiography/radionuclide imaging;Brain/pathology/radiography/radionuclide imaging;Dementia/ diagnosis/radiography/radionuclide imaging;Dementia, Vascular/diagnosis/radiography/radionuclide imaging;Humans;Magnetic Resonance Imaging;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Oksengard, A. R.;Haakonsen, M.;Dullerud, R.;Babovic, A.;Laake, K.;Engedal, K.",2002,Mar 10,,0,
2153,An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia,"The pathogenesis of dementia associated with Fabry disease was examined neuropathologically in an autopsy case. The patient was a 47-year-old computer programmer who developed renal failure at the age of 36, necessitating peritoneal dialysis, and thereafter suffered in succession episodic pulmonary congestion, bradyacusia, heart failure, and dementia, before dying of acute myocardial infarction. MRI of the brain demonstrated leuko-araiosis. The CNS parenchyma showed widespread segmental hydropic swelling of axons in the bilateral cerebral and cerebellar deep white matter in addition to neuronal ballooning due to glycolipid storage in a few restricted nuclei and multiple tiny lacunae. Hydropic axonal swelling was also sparsely distributed in the pyramidal tract, pedunculus cerebellaris superior and brachium colliculi inferioris, but wallerian degeneration of these tracts was absent. Additional features included angiopathy of the subarachnoidal arteries due to Fabry disease, such as medial thickening resulting from glycolipid deposition in smooth muscle cells (SMCs) and adventitial fibrosis with lymphocytic infiltration, together with widespread subtotal or total replacement of medial SMCs by fibrosis, associated with prominent intimal fibrous thickening and undulation of the internal elastic membrane of medium-sized (1000-100 μm diameter) arteries. The findings in this case suggest that axonopathic leukoencephalopathy due to multisegmental hydropic swelling of axons in the bilateral cerebral deep white matter is responsible for the dementia associated with Fabry disease, and may be caused by ischemia resulting from widespread narrowing and stiffening of medium-sized subarachnoidal arteries and progressive heart failure. © 2008 Japanese Society of Neuropathology.",alpha galactosidase;glycolipid;acute heart infarction;adult;artery compliance;artery diameter;artery intima proliferation;article;autopsy;bradyacusia;brain artery;brain region;case report;cell nucleus;cell swelling;central nervous system;cerebellum;cerebrovascular disease;dementia;disease association;enzyme replacement;Fabry disease;hearing disorder;heart failure;human;inferior colliculus brachium;kidney failure;leukoaraiosis;lipid storage;lung congestion;lymphocytic infiltration;male;nerve degeneration;neuroimaging;neurologic examination;neuropathology;nuclear magnetic resonance imaging;parenchyma;pedunculus cerebellaris superior;peritoneal dialysis;priority journal;pyramidal tract;smooth muscle fiber;subarachnoid space;vascular fibrosis;white matter,"Okeda, R.;Nisihara, M.",2008,,,0,
2154,An autopsy case of drug-induced diffuse cerebral axonopathic leukoencephalopathy: The pathogenesis in relation to reversible posterior leukoencephalopathy syndrome,"An autopsy case of diffuse axonopathic leukoencephalopathy induced by drug treatment is reported. A 70-year-old woman with multiple myeloma developed encephalopathy several days after completing a course of intravenous human immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF), and died within I month. T2-weighted MRI demonstrated multifocal high-signal areas in the bilateral cerebral white matter, especially in the right frontal lobe. Neuropathologically, multifocal hydropic axonal swelling with a poor glial reaction was recognized diffusely in the bilateral deep cerebral white matter, being especially marked in the frontal lobe. The cortex, subcortical U-fibers, corpus callosum, and anterior commissure were spared. The cerebellar white matter also showed similar changes, albeit less marked, but the brainstem was spared. Microscopically, the myeloma involvement of the CNS was limited to the dura, and the cerebral arteries showed slight atherosclerosis, but neither thrombi nor angitis. This case, although ultimately fatal, neurologically and neuroradiologically resembled reversible posterior leukoencephalopathy syndrome (RPLS) induced by IVIg and/or G-CSF, and the nature and selective distribution of the neuropathological changes suggested that the pathogenesis involved vasospasm of the bilateral internal carotid artery and the main trunks of the cerebral arteries, due to unknown cause, inducing ischemia in the deep white matter, which is supplied by long nutrient arteries. © 2007 Japanese Society of Neuropathology.",cilastatin plus imipenem;cyclophosphamide;doxorubicin;granulocyte colony stimulating factor;human immunoglobulin;pamidronic acid;piperacillin;prednisolone;recombinant granulocyte colony stimulating factor;sarcolysin;tobramycin;vincristine;aged;article;autopsy;brain atherosclerosis;brain disease;brain vasospasm;case report;computer assisted tomography;dementia;diffuse cerebral axonopathy leukoencephalopathy;diffusion weighted imaging;female;fever;finger tremor;frontal lobe;gait disorder;granulocytopenia;human;leukocyte count;leukoencephalopathy;multiple myeloma;nerve fiber degeneration;neurologic disease;neuropathology;neuroradiology;pancytopenia;pathogenesis;posterior reversible encephalopathy syndrome;priority journal;thrombocytopenia;white matter;aredia;tienam,"Okeda, R.;Kawamoto, T.;Tanaka, E.;Shimizu, H.",2007,,,0,
2155,Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: A case presented brain calcification and corpus callosum atrophy from over 10 years before the onset of dementia,"A 44-year-old man made many mistakes at work over a year. Eleven years prior, he had had medical examination with headache. He presented with symptoms consistent with frontal lobe dysfunction including cognitive decline, and bilateral pyramidal signs. Brain MRI showed cerebral atrophy, localized atrophy of corpus callosum, asymmetrical white matter lesions and multiple cystic lesions. CT images showed bilateral calcifications in the parietal subcortical white matter. Reconstructed sagittal CT images showed bilateral calcifications in the frontal white matter adjacent to the anterior horns of the lateral ventricles, which had a symmetrical “stepping stone appearance” in the frontal pericallosal regions. The brain MRI and CT images performed 11 years prior already showed evidence of similar findings including corpus callosum atrophy, multiple cystic lesions, and calcifications in the parietal subcortical white matter. Similar cystic lesions and calcifications were also observed in the frontal white matter adjacent to the anterior horns of the lateral ventricles However, the changes in the brain associated with atrophy and white matter lesions at this stage were mild. Genetic analysis revealed a novel mutation, p.R782C, in the exon 18 of the colony stimulating factor 1 receptor (CSF1R) gene. The CSF1R gene encodes the colony stimulating factor 1 receptor protein. This mutation was not observed in the patient's parents. Therefore, this mutation is considered to be a de novo mutation. He was diagnosed as having adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).",colony stimulating factor 1 receptor;colony stimulating factor receptor;unclassified drug;adult;article;brain atrophy;brain calcification;brain cyst;brain dysfunction;case report;clinical article;cognitive defect;computer assisted tomography;corpus callosum;CSF1R gene;dementia;disease severity;exon;frontal lobe;gene mutation;genetic analysis;glia cell;headache;human;leukoencephalopathy;male;medical examination;nuclear magnetic resonance imaging;onset age;pyramidal sign;spheroid cell;symptom;white matter lesion,"Okamoto, M.;Takeshita, J.;Takahashi, K.;Tanaka, A.;Yoshida, K.;Kuriyama, M.",2017,,10.5692/clinicalneurol.cn-001072,0,
2156,Educational history is an independent predictor of cognitive deficits and long-term survival in postacute patients with mild to moderate ischemic stroke,"BACKGROUND AND PURPOSE: Poststroke cognitive decline and white matter lesions (WML) are related to poor poststroke survival. Whether cognitive reserve as reflected by educational history associates with cognitive decline, recurrent strokes, and poststroke mortality independent of WML is not known. METHODS: A total of 486 consecutive acute mild/moderate ischemic stroke patients subjected to comprehensive neuropsychological assessment (n=409) and magnetic resonance imaging (n=395) 3 months poststroke were included in the study and followed-up for up to 12 years. Odds ratios (OR) for logistic and hazard ratios for Cox regression analyses are reported (OR and hazard ratio</=1 indicates a beneficial effect). RESULTS: Long educational history (per tertile) was associated with lower frequency of executive dysfunction in models adjusted for age, sex, marital status, and stroke severity (OR, 0.75; P<0.05) but not when adding WML as a covariate. In contrast, educational history was independently associated with less memory impairment (OR, 0.67; P<0.01), aphasia (OR, 0.69; P<0.05), visuospatial and constructive deficits (OR, 0.70; P<0.05), Mini-Mental State Examination score<25 (OR, 0.53; P<0.0001), and dementia (OR, 0.66; P<0.01). In Cox regression analysis, educational history was not associated with recurrent strokes, but it associated independently with favorable poststroke survival (hazard ratio, 0.86; P<0.05). CONCLUSIONS: Long educational history associates with less poststroke cognitive deficits, dementia, and favorable long-term survival independent of age, gender, marital status, stroke severity, and WML in patients with mild/moderate ischemic stroke. This supports the hypothesis that educational history as a proxy indicator of cognitive reserve protects against deficits induced by acute stroke.","Aged;Aged, 80 and over;Cognition Disorders/ epidemiology/ etiology;Educational Status;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Prognosis;Proportional Hazards Models;Stroke/ complications/ mortality","Ojala-Oksala, J.;Jokinen, H.;Kopsi, V.;Lehtonen, K.;Luukkonen, L.;Paukkunen, A.;Seeck, L.;Melkas, S.;Pohjasvaara, T.;Karhunen, P.;Hietanen, M.;Erkinjuntti, T.;Oksala, N.",2012,Nov,10.1161/strokeaha.112.667618,0,
2157,Correlation between contingent negative variation and regional cerebral blood flow,"The relationship between contingent negative variation (CNV) and regional cerebral blood flow was investigated, using the stable xenon computed tomography method. Seventeen cases of chronic multiple cerebral infarction in the perforating artery areas (vascular dementia, mean age 67.0), 6 cases of Alzheimer's disease (mean age 69.5) and 8 healthy controls (mean age 62.5) were studied. Regional cerebral blood flows in the frontal, temporal, parietal and occipital cortex, frontal, temporal and occipital white matter, caudate nucleus, putamen and thalamus were measured: The amplitude of early CNV was significantly smaller in the vascular dementia group than in the healthy control group. The blood flows in the parietal cortex and thalamus were significantly lower in the vascular dementia group than in the healthy control group. There was a significant positive correlation between the amplitude of early CNV and frontal cortex blood flow. No significant correlations were present between the CNV and the other regional cerebral blood flows nor in healthy controls. The amplitude of CNV has been reported to be decreased in dementia. From the present study, the amplitude of early CNV was considered to be influenced by the blood flow in the frontal cortex.",adult;aged;Alzheimer disease;article;brain blood flow;clinical article;computer assisted tomography;contingent negative variation;controlled study;female;human;male;multiinfarct dementia;priority journal;tissue distribution,"Oishi, M.;Mochizuki, Y.",1998,,,0,
2158,Critical role of the right uncinate fasciculus in emotional empathy,"Objective: Common neurological diseases or injuries that can affect the right hemisphere, including stroke, traumatic brain injury, and frontotemporal dementia, disrupt emotional empathy - the ability to share in and make inferences about how other people feel. This impairment negatively impacts social interactions and relationships. Accumulating evidence indicates that emotional empathy depends on coordinated functions of orbitofrontal cortex, anterior insula, anterior cingulate, temporal pole, and amygdala, but few studies have investigated effects of lesions to white matter tracts that connect these structures. We tested the hypothesis that percentage damage to specific white matter tracts connecting these gray matter structures predicts error rate in an emotional empathy task after acute right hemisphere ischemic stroke. Methods: We used multivariate linear regression with percentage damage to 8 white matter tracts, age, and education as independent variables and error rate on emotional empathy as the dependent variable to test a predictive model of emotional empathy in 30 patients with acute ischemic right hemisphere stroke. Results: Percentage damage to 8 white matter tracts along with age and education predicted the error rate in emotional empathy, but only percentage damage to the uncinate fasciculus was independently associated with error rate. Participants with right uncinate fasciculus lesions were significantly more impaired than right hemisphere stroke patients without uncinate fasciculus lesions in the emotional empathy task. Interpretation: The right uncinate fasciculus plays an important role in the emotional empathy network. Patients with lesions in this network should be evaluated for empathy, so that deficits can be addressed.",adult;article;brain ischemia;clinical article;controlled study;empathy;error;gray matter;human;neuroimaging;nuclear magnetic resonance imaging;priority journal;right hemisphere;stroke patient;uncinate fasciculus;white matter;white matter lesion,"Oishi, K.;Faria, A. V.;Hsu, J.;Tippett, D.;Mori, S.;Hillis, A. E.",2015,,,0,
2159,Atlas-based whole brain white matter analysis using large deformation diffeomorphic metric mapping: application to normal elderly and Alzheimer's disease participants,"The purpose of this paper is to establish single-participant white matter atlases based on diffusion tensor imaging. As one of the applications of the atlas, automated brain segmentation was performed and the accuracy was measured using Large Deformation Diffeomorphic Metric Mapping (LDDMM). High-quality diffusion tensor imaging (DTI) data from a single-participant were B0-distortion-corrected and transformed to the ICBM-152 atlas or to Talairach coordinates. The deep white matter structures, which have been previously well documented and clearly identified by DTI, were manually segmented. The superficial white matter areas beneath the cortex were defined, based on a population-averaged white matter probability map. The white matter was parcellated into 176 regions based on the anatomical labeling in the ICBM-DTI-81 atlas. The automated parcellation was achieved by warping this parcellation map to normal controls and to Alzheimer's disease patients with severe anatomical atrophy. The parcellation accuracy was measured by a kappa analysis between the automated and manual parcellation at 11 anatomical regions. The kappa values were 0.70 for both normal controls and patients while the inter-rater reproducibility was 0.81 (controls) and 0.82 (patients), suggesting ""almost perfect"" agreement. A power analysis suggested that the proposed method is suitable for detecting FA and size abnormalities of the white matter in clinical studies.","Adult;Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/ pathology;Artificial Intelligence;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Pattern Recognition, Automated/ methods;Reference Values;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Oishi, K.;Faria, A.;Jiang, H.;Li, X.;Akhter, K.;Zhang, J.;Hsu, J. T.;Miller, M. I.;van Zijl, P. C.;Albert, M.;Lyketsos, C. G.;Woods, R.;Toga, A. W.;Pike, G. B.;Rosa-Neto, P.;Evans, A.;Mazziotta, J.;Mori, S.",2009,Jun,,0,
2160,Multi-modal MRI analysis with disease-specific spatial filtering: initial testing to predict mild cognitive impairment patients who convert to Alzheimer's disease,"BACKGROUND: Alterations of the gray and white matter have been identified in Alzheimer's disease (AD) by structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). However, whether the combination of these modalities could increase the diagnostic performance is unknown. METHODS: Participants included 19 AD patients, 22 amnestic mild cognitive impairment (aMCI) patients, and 22 cognitively normal elderly (NC). The aMCI group was further divided into an ""aMCI-converter"" group (converted to AD dementia within 3 years), and an ""aMCI-stable"" group who did not convert in this time period. A T(1)-weighted image, a T(2) map, and a DTI of each participant were normalized, and voxel-based comparisons between AD and NC groups were performed. Regions-of-interest, which defined the areas with significant differences between AD and NC, were created for each modality and named ""disease-specific spatial filters"" (DSF). Linear discriminant analysis was used to optimize the combination of multiple MRI measurements extracted by DSF to effectively differentiate AD from NC. The resultant DSF and the discriminant function were applied to the aMCI group to investigate the power to differentiate the aMCI-converters from the aMCI-stable patients. RESULTS: The multi-modal approach with AD-specific filters led to a predictive model with an area under the receiver operating characteristic curve (AUC) of 0.93, in differentiating aMCI-converters from aMCI-stable patients. This AUC was better than that of a single-contrast-based approach, such as T(1)-based morphometry or diffusion anisotropy analysis. CONCLUSION: The multi-modal approach has the potential to increase the value of MRI in predicting conversion from aMCI to AD.",,"Oishi, K.;Akhter, K.;Mielke, M.;Ceritoglu, C.;Zhang, J.;Jiang, H.;Li, X.;Younes, L.;Miller, M. I.;van Zijl, P. C.;Albert, M.;Lyketsos, C. G.;Mori, S.",2011,,10.3389/fneur.2011.00054,0,
2161,Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5,"We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.",,"Ohtake, H.;Shimohata, T.;Terajima, K.;Kimura, T.;Jo, R.;Kaseda, R.;Iizuka, O.;Takano, M.;Akaiwa, Y.;Goto, H.;Kobayashi, H.;Sugai, T.;Muratake, T.;Hosoki, T.;Shioiri, T.;Okamoto, K.;Onodera, O.;Tanaka, K.;Someya, T.;Nakada, T.;Tsuji, S.",2004,11,,0,
2162,Cerebral blood flow patterns in patients with leukoaraiosis and lacunar infarction,"We compared the incidence of risk factors (such as hypertension, diabetes mellitus, hyperlipidemia, hematocrit, atrial fibrillation) and local cerebral blood flow between patients with lacunar infarction associated with leukoaraiosis (LA) in the centrum semiovale (LACS) and those with periventricular white matter lesions (PVWMLs) on magnetic resonance imagings (MRI). Only atrial fibrillation was more frequently seen in LACS (p < 0.05), but the incidence of other risk factors for cerebrovascular disease was not different between the two patient groups. Demented patients were older than those with preserved intelligence in both groups. Local cerebral blood flow was compared between patients with and without dementia by single photon emission computed tomography using N-isopropyl-p-123I iodoamphetamine (IMP). The cerebral: cerebellar IMP uptake ratio (%) was used as a measure of relative cerebral perfusion. Compared with normal controls the demented patients with PVWMLs showed a significant reduction in local cerebral blood flow in the parietal area (p < 0.05) and the basal gray region (p < 0.05), and those with LACS in the frontal area (p < 0.05) and the basal gray region (p < 0.05). A significant positive correlation was found between local cerebral blood flow and dementia rating scales in the temporal and parietal areas in PVWMLs, and in the frontal area in LACS. These results suggest that most patients with LACS may represent vascular dementia of Binswanger type, and some demented patients with PVWMLs may have Alzheimer type dementia.",4 iodoamphetamine;iofetamine i 123;adult;aged;article;Binswanger encephalopathy;brain blood flow;brain infarction;controlled study;female;human;intravenous drug administration;major clinical study;male;nuclear magnetic resonance;single photon emission computer tomography,"Ohsawa, N.;Takahashi, S.;Yonezawa, H.",1994,,,0,
2163,High-resolution SPECT to assess hippocampal perfusion in neuropsychiatric diseases,"The purpose of this study is to clarify the changes of hippocampal perfusion in neuropsychiatric diseases, including dementia, compared with control subjects, and to correlate hippocampal perfusion with the dementia rating scale and the severity of memory disturbance in patients with these diseases. Methods: A total of 45 right-handed patients were investigated (13 with dementia of Alzheimer type, 6 with multi-infarct dementia, 4 with progressive dementia with motor neuron disease (MND), 3 with transient global amnesia, 5 with other diseases and 14 control subjects). Regional cerebral blood flow (rCBF) in the parietal cortex and hippocampus was evaluated by high-resolution SPECT technique with HMPAO in all subjects. Results: The rCBF measurements in the bilateral parietal cortices and hippocampus were lower in dementia of Alzheimer type and multiinfarct dementia patients than in controls. Hypoperfusion in the hippocampus was a more sensitive marker than hypoperfusion in the parietal cortex in diagnosing dementia of Alzheimer type. Hippocampal hypoperfusion was observed in demented patients regardless of etiology and in patients having memory disturbance without dementia, such as transient global amnesia. Finally, hippocampal hypoperfusion reflected the severity of dementia and memory disturbance regardless of etiology. Conclusion: The rCBF image with high-resolution SPECT system may be useful in assessing the extent of dementia and memory disturbance in patients with neuropsychiatric diseases.",,"Ohnishi, T.;Hoshi, H.;Nagamachi, S.;Jinnouchi, S.;Flores, I. L. G.;Futami, S.;Watanabe, K.",1995,1995,,0,
2164,Association between arterial stiffness and cerebral white matter lesions in community-dwelling elderly subjects,"The presence of cerebral white matter lesions (WMLs) on MRI is suggested to be a predictive factor for vascular dementia and stroke. To investigate the relationship between arterial stiffness and WMLs, we performed brain MRI to evaluate the presence of two subtypes of WML-periventricular hyperintensities (PVH) and deep white matter lesions (DWML)-and furthermore, determined the brachial-ankle pulse wave velocity (ba-PWV) as a marker of arterial stiffness in 132 elderly asymptomatic subjects (49 men and 83 women, 70.3+/-9.0 years). PVH and DWML were observed in 41 (31.0%) and 53 (40.2%) subjects, respectively. The ba-PWV values were significantly greater in subjects with PVH than in those without. DWML also tended to be associated with ba-PWV, but the correlation was not statistically significant. In multiple logistic regression analysis, age and decreased DBP were independently associated with PVH. ba-PWV was also detected as an independent factor for the appearance of PVH (adjusted odds ratio: 2.84, p=0.015) but not DWML. These results indicate that the increase in arterial stiffness contributes to the pathogenesis of PVH rather than DWML. Although further study is needed to clarify the difference between WML subtypes, our study suggests that the measurement of ba-PWV is a simple and useful tool for detecting cerebral arterial dysfunction.","Aged/*physiology;Aged, 80 and over;Aging/physiology;Arteries/*pathology;Blood Pressure/physiology;Brain/*pathology;Cerebral Ventricles/pathology;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Regional Blood Flow/physiology","Ohmine, T.;Miwa, Y.;Yao, H.;Yuzuriha, T.;Takashima, Y.;Uchino, A.;Takahashi-Yanaga, F.;Morimoto, S.;Maehara, Y.;Sasaguri, T.",2008,Jan,10.1291/hypres.31.75,0,
2165,[A patient with Creutzfeldt-Jakob disease supported by home medical care from the stage of disease progression to death through hospital-clinic cooperation and medical-welfare cooperation],"The patient was a 63-year-old woman who presented with slowness of speech after cerebral infarction. Diffusion-weighted MR images and investigations of cerebrospinal fluid showed abnormal values, and the patient was diagnosed as having sporadic Creutzfeldt-Jakob disease(CJD). This is an intractable disease and affects one in one million people; it progresses relatively rapidly, eventually resulting in death. For procedures such as intravenous fluid replacement and the treatment of pressure sores, we require thorough hand washing, eye protection, and disposal of gloves and dressings by incineration. It is desirable for patients to spend the limited amount of time available to them peacefully at home with their family. Visiting physicians and nurses need to take the initiative in sharing information obtained from the CJD infection control guidelines and core hospitals with welfare personnel such as caregivers, in order to provide correct information on all aspects of patient care and the management of this disease in the home environment. Excellent supportive care was provided for the patient at home, and she passed away with her family by her side.",case report;Creutzfeldt Jakob disease;disease course;fatality;female;home care;human;middle aged;nuclear magnetic resonance imaging;patient care,"Ohashi, K.;Kamizasa, H.;Suzuki, T.;Kinomoto, K.;Murakami, Y.;Ito, T.;Hadatsuki, H.;Onaka, T.;Takubo, H.",2014,,,0,2166
2166,A patient with Creutzfeldt-Jakob disease supported by home medical care from the stage of disease progression to death through hospital-clinic cooperation and medical-welfare cooperation,"The patient was a 63-year-old woman who presented with slowness of speech after cerebral infarction. Diffusion-weighted MR images and investigations of cerebrospinal fluid showed abnormal values, and the patient was diagnosed as having sporadic Creutzfeldt-Jakob disease(CJD). This is an intractable disease and affects one in one million people; it progresses relatively rapidly, eventually resulting in death. For procedures such as intravenous fluid replacement and the treatment of pressure sores, we require thorough hand washing, eye protection, and disposal of gloves and dressings by incineration. It is desirable for patients to spend the limited amount of time available to them peacefully at home with their family. Visiting physicians and nurses need to take the initiative in sharing information obtained from the CJD infection control guidelines and core hospitals with welfare personnel such as caregivers, in order to provide correct information on all aspects of patient care and the management of this disease in the home environment. Excellent supportive care was provided for the patient at home, and she passed away with her family by her side.",,"Ohashi, K.;Kamizasa, H.;Suzuki, T.;Kinomoto, K.;Murakami, Y.;Ito, T.;Hadatsuki, H.;Onaka, T.;Takubo, H.",2014,1,,0,
2167,Clinical and radiological features of stroke patients with poor outcomes who do not receive intravenous thrombolysis because of mild symptoms,"Background and Aims: A substantial proportion of patients who did not receive intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA), solely because of mild symptoms, can show poor outcome. The aim of our study was to analyze clinical and radiological features of the patients. Methods: We enrolled 72 patients between 2007 and 2009 who presented to our hospital within 3 h after stroke onset and who did not receive rtPA therapy solely because of mild symptoms (NIHSS score of ≤4 at rtPA decision), and examined detailed characteristics of patients with poor outcomes. Poor outcome was defined as a modified Rankin Scale score of ≥2 at 3 months after the stroke. Results: Eleven of 72 patients (15%) had poor outcomes. Major vessel occlusion was observed in 7 of the 11 patients. Neurological deterioration after admission was main reason for poor outcome. Infarct expansion in 6 patients (2 large artery diseases and 4 small vessel diseases) and distal embolism by clot migration in 3 patients led to neurological deterioration. Conclusions: Clinical and radiological features of mild stroke patients with poor outcomes, who did not receive rtPA therapy, were identified. In such patients, intravenous thrombolysis may be justified.",alteplase;adult;aged;article;blood clot lysis;blood vessel occlusion;brain infarction;cerebrovascular accident;clinical feature;diffusion weighted imaging;disease severity;female;human;magnetic resonance angiography;major clinical study;male;mental deterioration;middle aged;National Institutes of Health Stroke Scale;neuroradiology;priority journal;Rankin scale;stroke patient;symptomatology;treatment outcome,"Ohara, T.;Nagakane, Y.;Tanaka, E.;Morii, F.;Koizumi, T.;Yamamoto, Y.",2013,,,0,
2168,A clinical and neuropathological study of an unusual case of sporadic tauopathy. A variant of corticobasal degeneration?,"We report a sporadic case of tauopathy with unusual clinical and neuropathological features. The patient presented with progressive symmetric rigid-akinetic parkinsonism and dementia of the subcortical type. Magnetic resonance imaging of the brain revealed atrophy resembling multiple system atrophy. The level of cerebrospinal fluid tau protein phosphorylated at serine 199 was markedly elevated. The autopsy revealed more glial than neuronal tauopathy, with much heavier involvement of subcortical white matter and the brainstem than of the cerebral cortex. Analysis of dephosphorylated tau revealed that hyperphosphorylated four-repeat tau isoforms were deposited in the brain of the patient. Despite morphological and biochemical resemblance to a certain form of familial fronto-temporal dementia, no mutation of the tau gene including exon 10 could be found. Our findings, taken together with those in previous similar case reports, indicate that the case represents an atypical form of corticobasal degeneration or a new variant of sporadic tauopathy. © 2002 Elsevier Science Ireland Ltd. All rights reserved.",,"Ohara, S.;Tsuyuzaki, J.;Oide, T.;Arai, H.;Higuchi, S.;Hasegawa, M.;Iwatsubo, T.",2002,13,,0,
2169,"A case of intra-axial multiple cavernous angiomas, presented with dementia and cerebellar signs","We reported a case of intra-axial multiple cavernous angiomas, presented with dementia and cerebellar signs. The patient, a right-handed 73-year-old woman, showed gait disturbances, tremor increased while writing and hypoactivity at the age of 71. Treatment with 1-dopa was not effective. At the age of 73, she was diagnosed as having intra-axial multiple cavernous angiomas on the gradient echo MRI study, which demonstrated large numbers of small low density areas (small dots) in the cerebellar cortex and moderate numbers of those in the cerebral cortices. Those small dots were not detected in the basal ganglia, the brain stem, and increased the thalamus. She clinically showed cerebellar signs, such as dysmetria, adiadochokinesia, and tremor worsening in the course of writings, in additions to the constructural apraxia, disturbances of writing, and severe perseverations. Those symptoms slightly fluctuated. However, she did not show any character changes. The results of Wisconsin card sorting test and Trial making test A were different from those usually seen in dementia with multiple infarctions in the cerebral white matters and basal ganglia. Although her cerebellar signs are considered to be due to numerous small dots in the cerebellar cortex, her parietal symptoms could not be understood by slight parietal changes such as hypoperfusions of SPECT, cerebral small dots, and infarctions in the white matters. We speculated that, by interactions between the cerebellar dysfunctions and slight parietal dysfunctions, she developed the parietal symptoms described above, which differed from dementia or Parkinsonism due to multiple cerebral infarctions, and which were characterized by slight fluctuations and alleviations with habituation.",aged;article;brain tumor;case report;cavernous hemangioma;cerebellum disease;dementia;female;human,"Ohara, K.;Shinjo, T.;Nishii, R.;Takeda, K.;Kokai, M.;Morita, Y.",2002,,,0,
2170,Association between urine protein/creatinine ratio and cognitive dysfunction in Lewy body disorders,"BACKGROUND: Impaired renal function and proteinuria have been associated with cognitive impairment and dementia. Chronic kidney disease is considered to be an independent risk factor for Lewy body spectrum disorders (LBD). However, few studies have mentioned an association between proteinuria and cognition in LBD. We investigated the relationship between proteinuria and cognitive dysfunction in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: Among 186 patients with LBD, 53 had PD-normal cognition (PD-NC), 76 had PD-mild cognitive impairment (PD-MCI), 43 had PD-dementia (PDD) and 14 had DLB. The urine protein/creatinine ratio was calculated using the spot urine test and brain magnetic resonance scans was obtained in all patients. RESULTS: The urine protein/creatinine ratio was significantly higher in patients with PDD and DLB than in those with PD-MCI, PD-NC patients and healthy controls, and was correlated with white matter hyperintensities on magnetic resonance imaging. All abnormal neuropsychological test results were associated with increased urine protein/creatinine ratio. After controlling for age, education, symptom duration, diabetes mellitus, hypertension, and parkinsonian motor severity, the urine protein/creatinine ratio was significantly associated with decreased cognition. CONCLUSION: The urine protein/creatinine ratio was associated with cognitive status in LBD. These finding suggests that increased protein excretion is associated with cognitive dysfunction in patients with LBD.",,"Oh, Y. S.;Kim, J. S.;Park, H. E.;Song, I. U.;Park, J. W.;Yang, D. W.;Son, B. C.;Lee, S. H.;Lee, K. S.",2016,Mar 15,10.1016/j.jns.2016.01.061,0,
2171,Massive pontine microbleeds in a patient with CADASIL,,Notch3 receptor;adult;article;basal ganglion;brain hemorrhage;CADASIL;case report;Clinical Dementia Rating;disease duration;DNA determination;dysarthria;female;gene mutation;headache;hemiparesis;human;middle aged;Mini Mental State Examination;mutational analysis;neurologic examination;Notch3 gene;nuclear magnetic resonance imaging;priority journal;thalamus;white matter,"Oh, S. I.;Kim, S. H.;Kim, H. J.",2014,,,0,
2172,Aspirin-associated intracerebral hemorrhage in a patient with CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease characterized by ischemic stroke, cognitive impairment, migraine and neuropsychological deficit. Although intracerebral hemorrhage (ICH) has been described in patients with CADASIL, the cause of such ICH is still unknown. We present a 39-year-old man with CADASIL who had two years history of untreated hypertension. In this patient, acute ICH developed only two weeks after the initiation of aspirin. Brain images demonstrated a 3 cm × 3 cm hyperacute ICH in the left temporal lobe at the site of previous old hemorrhage. The presence of cerebral microbleed and use of antithrombotics may be associated with development of ICH in patients with CADASIL. © 2007 Elsevier B.V. All rights reserved.",,"Oh, J. H.;Lee, J. S.;Kang, S. Y.;Kang, J. H.;Choi, J. C.",2008,April,,0,
2173,Effect of cardiac function on cognition and brain structural changes in dementia,"BACKGROUND AND PURPOSE: Cardiovascular risk factors are considered to also be risk factors for dementia. Recent studies have shown that the prevalence of cognitive dysfunction is high in patients with cardiac diseases. However, few studies have investigated the influence of cardiac function on cognition and brain structural changes in dementia. The aims of this study were to determine the relationship between cardiac and cognitive function, and to characterize any structural changes in the brain that could be caused by cardiac function in patients with dementia. METHODS: Dementia patients (n=93) were recruited prospectively with checking for the presence of vascular risk factors such as hypertension. Cognitive function was measured by the Mini-Mental State Examination, modified Mini-Mental State test, and Korean version of the Dementia Rating Scale. Brain magnetic resonance imaging was conducted to evaluate the cerebral white-matter changes (WMC), ventricular dilation, and cortical and hippocampal atrophy. Cardiac function was evaluated using two-dimensional echocardiography. We divided the patients into two groups according to the presence (+) or absence (-) of WMC. RESULTS: In the entire cohort, the size of the left atrium (LA) was positively correlated with the degree of WMC, irrespective of age (p<0.05). The LA was larger in the WMC (+) group (n=42) than in the WMC (-) group. General cognitive function was significantly lower in the WMC (+) group than in the WMC (-) group. Subjects with an enlarged LA tended to exhibit lower cognitive function and more-severe cerebral WMC. CONCLUSIONS: Cardiac dysfunction represented by LA enlargement could be related to cognitive decline and WMC of the brain resulting from impairment of the cerebral hemodynamic process in dementia.",,"Oh, J. E.;Shin, J. W.;Sohn, E. H.;Jung, J. O.;Jeong, S. H.;Song, H. J.;Kim, J. M.;Lee, A. Y.",2012,Jun,10.3988/jcn.2012.8.2.123,0,
2174,Prominent mental symptoms and obscure physical signs; report of six cases with temporal lobe lesions,"Six cases of temporal lobe lesions with prominent mental symptoms and without clear physical signs are reported. Case one, a right handed 53 year old female, suffered from speech disturbances and impaired mentation. The initial diagnosis had been presenile dementia. But closer examination confirmed the presence of transcortical aphasia. With the help of CT scans the final diagnosis of metastatic brain tumor was established with a principal lesion in the left temporal lobe. Case two, a 61 year old right handed male, developed headache, speech disturbances and mild left hemiparesis. Neuropsychological examination revealed amnestic aphasia. The patient was operated for an astrocytoma which was situated in the right temporal lobe. In subsequent course of radiation therapy violent behavior was often observed. Case three, a right handed 59 year old female, experienced aphasic seizures which were characterized by a loss of auditory language comprehension and the spontaneous production of incoherent words and would last about 10 seconds. A left-sided sphenoidal ridge meningioma was removed. Case four, a right handed 67 year old female, had a sudden fall followed by nausea, vomiting, headache and confusion. In a hospital she would shriek, become angry and did not cooperate. An autopsy revealed putamenal hemorrhage rupturing into the left temporal lobe. Case five, a right handed 63 year old man, began to behave abnormally. Agitation and violent behavior were also present. A glioblastoma of the right temporal lobe was found and eventually removed. Case six, a right handed 39 year old male, had been recovering from an initial infarction of the right temporo-occipital area due to Moyamoya disease when the second infarction destroyed the left temporo occipital area. Cortical blindness, and oral tendency, as well as violent behavior developed. Thus, aphasias such as the transcortical sensory type or amnesic type which was crossed, were major symptoms in the first two cases. These atypical aphasias have to be kept in mind when apparently demented patients are encountered. Aphasic seizure in case 3 was unusual but the proper diagnosis pointed to the temporal lobe lesion also. Violent behavior was characteristic in the last three patients. Although a responsible structure for violent behavior is still disputed, our present experience suggests the importance of temporal lobe lesions. When patients with prominent mental symptoms but with obscure physical signs are encountered, a possibility of temporal lobe lesion has to be considered.",aphasia;brain tumor;central nervous system;major clinical study;moyamoya disease;seizure;temporal lobe,"Ogura, J.;Mori, E.;Ohsumi, Y.",1979,,,0,
2175,Association of cerebral small vessel disease with delusions in patients with Alzheimer's disease,"Background Cerebral small vessel disease (SVD) is frequently observed in patients with Alzheimer's disease (AD). However, the association between SVD and clinical symptoms exhibited by patients with AD remains unclear. This study examined the association of SVD as observed on magnetic resonance imaging (MRI) with behavioural and psychological symptoms of dementia and cognitive function of patients with probable AD. Methods A total of 163 consecutive patients (55 men, 108 women) with probable AD were included in this cross-sectional study of a prospective cohort. Patients were divided into two groups based on the presence or absence of cerebral SVD [white matter hyperintensities (WMH) grade 0/1 (Fazekas scale) and no lacunes: SVD absent, WMH grade 2/3 (Fazekas scale) or the number of lacunes ≥1: SVD present]. Cognitive functions were assessed using the Mini mental state examination, word recall and recognition subtests in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, as well as the letter fluency task and the category fluency task. Psychiatric symptoms were rated according to Neuropsychiatric Inventory. Results Patients with probable AD with cerebral SVD had significantly more delusions and depression than those without SVD. No significant differences were observed in other neuropsychiatric symptoms, MMSE or word recall and recognition tests between both groups. Conclusions Our results suggest that cerebral SVD observed on MRI of patients with AD is associated with delusions and depression. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.",,"Ogawa, Y.;Hashimoto, M.;Yatabe, Y.;Kaneda, K.;Honda, K.;Yuuki, S.;Hirai, T.;Ikeda, M.",2013,January,,0,
2176,A case of Charles Bonnet syndrome following syphilitic optic neuritis,"Charles Bonnet syndrome refers to visual hallucinations in patients with visual acuity loss or visual field loss without dementia. We report a case of Charles Bonnet syndrome following syphilitic optic neuritis. A 62-year-old man was admitted to our hospital suffering acute bilateral visual loss in a few months. On admission, he was almost blind and his optic discs were found to be atrophic on fundoscopy. In addition to increased cell counts and protein concentration in cerebrospinal fluid (CSF), serum and CSF rapid plasma reagin tests were positive. A diagnosis of syphilitic optic neuritis was made and he was treated with intravenous penicillin G (24 million units per day for 14 days) without any recovery. After treatment finished, he began to experience complex, vivid, elaborate and colored visual hallucinations. He recognized these visions as unreal and felt distressed by them. No cognitive impairment was observed on several neuropsychological tests. We diagnosed the patient as suffering from Charles Bonnet syndrome. Brain MRI revealed diffuse mild atrophy of the cerebral cortex and multiple T2 high signal intensity lesions in the deep cerebral white matter. Single photon emission computed tomography revealed decreased regional cerebral blood flow in bilateral medial occipital lobes. Administration of olanzapine resulted in a partial remission of visual hallucinations. Charles Bonnet syndrome following syphilitic optic neuritis is rare. In the present case, visual loss and dysfunction of bilateral medial occipital lobes may have triggered the visual hallucinations, which were alleviated by olanzapine.",olanzapine;penicillin G;adult;article;brain atrophy;brain cortex;case report;cerebrospinal fluid analysis;Charles Bonnet syndrome;human;male;neuropsychological test;neurosyphilis;nuclear magnetic resonance imaging;occipital lobe;ophthalmoscopy;optic neuritis;protein blood level;reagin test;single photon emission computer tomography;white matter,"Ogata, H.;Shigeto, H.;Torii, T.;Kawamura, N.;Ohyagi, Y.;Kira, J. I.",2011,,,0,
2177,Frontal white matter hyperintensity predicts lower urinary tract dysfunction in older adults with amnestic mild cognitive impairment and Alzheimer's disease,"AIM: Lower urinary tract symptoms often limit activities of daily life and impair quality of life in the elderly. The purpose of the present study was to determine whether regional white matter hyperintensity (WMH) can predict lower urinary tract symptoms in elderly with amnestic mild cognitive impairment or Alzheimer's disease. METHODS: The participants were 461 patients aged 65-85 years diagnosed with amnestic mild cognitive impairment or Alzheimer's disease. Patients and their caregivers were asked about symptoms of lower urinary tract symptoms (urinary difficulty, frequency and incontinence). Cognition, behavior and psychological symptoms of dementia and medication were evaluated. WMH and brain atrophy were analyzed using an automatic segmentation program. Regional WMH was evaluated in the frontal, parietal, temporal and occipital lobes. RESULTS: Patients with urinary incontinence showed significantly greater volume of WMH. WMH increased with age, especially in the frontal lobe. WMH in the frontal lobe was closely associated with urinary incontinence after adjustment for brain atrophy and classical confounding factors. CONCLUSIONS: Frontal WMH was a predictive factor for urinary incontinence in older adults with amnestic mild cognitive impairment or Alzheimer's disease. Urinary incontinence in demented older adults is not an incidental event, and careful insight into regional WMH on brain magnetic resonance imaging might greatly help in diagnosing individuals with a higher risk of urinary incontinence. Geriatr Gerontol Int 2016; 16: 167-174.",,"Ogama, N.;Yoshida, M.;Nakai, T.;Niida, S.;Toba, K.;Sakurai, T.",2016,Feb,10.1111/ggi.12447,0,
2178,Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and Alzheimer's disease,"OBJECTIVES: Preventive strategy for falls in demented elderly is a clinical challenge. From early-stage of Alzheimer's disease (AD), patients show impaired balance and gait. The purpose of this study is to determine whether regional white matter lesions (WMLs) can predict balance/gait disturbance and falls in elderly with amnestic mild cognitive impairment (aMCI) or AD. DESIGN: Cross-sectional. SETTINGS: Hospital out-patient clinic. PARTICIPANTS: One hundred sixty-three patients diagnosed with aMCI or AD were classified into groups having experienced falls (n = 63) or not (n = 100) in the previous year. MEASUREMENTS: Cognition, depression, behavior and psychological symptoms of dementia, medication, and balance/gait function were evaluated. Regional WMLs were visually analyzed as periventricular hyperintensity in frontal caps, bands, and occipital caps, and as deep white matter hyperintensity in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalamus, and brain stem. Brain atrophy was linearly measured. RESULTS: The fallers had a greater volume of WMLs and their posture/gait performance tended to be worse than nonfallers. Several WMLs in particular brain regions were closely associated with balance and gait impairment. Besides polypharmacy, periventricular hyperintensity in frontal caps and occipital WMLs were strong predictors for falls, even after potential risk factors for falls were considered. CONCLUSIONS: Regional white matter burden, independent of cognitive decline, correlates with balance/gait disturbance and predicts falls in elderly with aMCI and AD. Careful insight into regional WMLs on brain magnetic resonance may greatly help to diagnose demented elderly with a higher risk of falls.","Accidental Falls/*statistics & numerical data;Aged;Alzheimer Disease/*complications;Amnesia/*complications;Atrophy;Brain/*pathology;Cross-Sectional Studies;Female;Gait Disorders, Neurologic/etiology;Humans;*Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/*complications;Multivariate Analysis;Polypharmacy;Risk Factors;Sensitivity and Specificity;Surveys and Questionnaires;Alzheimer's disease;White matter lesions;amnestic mild cognitive impairment;falls","Ogama, N.;Sakurai, T.;Shimizu, A.;Toba, K.",2014,Jan,10.1016/j.jamda.2013.11.004,0,
2179,Impact of frontal white matter hyperintensity on instrumental activities of daily living in elderly women with Alzheimer disease and amnestic mild cognitive impairment,"BACKGROUND: Instrumental activities of daily living (IADL) start to decline during the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD). Cognitive and physical decline are involved in the loss of functional independence. However, little is known about AD-related neural change that leads to IADL impairment. The purpose of this study was to clarify the effects of regional white matter hyperintensity (WMH) on IADL impairment in persons with AD and aMCI. METHODS: The participants were 347 female subjects aged 65-85 years diagnosed with AD (n = 227), aMCI (n = 44) or normal cognition (n = 76). IADL was assessed by the Lawton Index. Cognition, mood and mobility function were evaluated by comprehensive geriatric assessment batteries. WMH and brain atrophy were analyzed with brain magnetic resonance imaging, using an automatic segmentation program. Regional WMH was measured in the frontal, temporal, occipital and parietal lobes. RESULTS: Ability to carry out IADL of shopping, food preparation, mode of transportation, responsibility for own medication, and ability to handle finances was obviously impaired in the early stage of AD. Frontal WMH was specifically associated with disability to do shopping and food preparation even after adjusting for several confounders including brain atrophy. CONCLUSIONS: IADL subcategories were differentially impaired along with cognitive status in persons with AD and aMCI. Frontal WMH was an important predictor of impaired ability to do shopping and food preparation. A preventive strategy for WMH might lead to suppression of IADL disability and slow the progression of AD.",,"Ogama, N.;Sakurai, T.;Nakai, T.;Niida, S.;Saji, N.;Toba, K.;Umegaki, H.;Kuzuya, M.",2017,,,0,
2180,Sexual dimorphism in healthy aging and mild cognitive impairment: a DTI study,"Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women.",Aged;Alzheimer Disease/physiopathology/radiography;Brain/*physiopathology/*radiography;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/*physiopathology/*radiography;Organ Size;*Sex Characteristics;Sex Factors,"O'Dwyer, L.;Lamberton, F.;Bokde, A. L.;Ewers, M.;Faluyi, Y. O.;Tanner, C.;Mazoyer, B.;O'Neill, D.;Bartley, M.;Collins, R.;Coughlan, T.;Prvulovic, D.;Hampel, H.",2012,,10.1371/journal.pone.0037021,0,
2181,Using support vector machines with multiple indices of diffusion for automated classification of mild cognitive impairment,"Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical.","Aged;Algorithms;Alzheimer Disease/diagnosis/pathology;Automation;Cognition Disorders/ diagnosis/pathology;Diagnosis, Computer-Assisted/ methods;Diffusion;Diffusion Tensor Imaging/ methods;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/pathology;Sensitivity and Specificity;Signal Processing, Computer-Assisted;Support Vector Machine","O'Dwyer, L.;Lamberton, F.;Bokde, A. L.;Ewers, M.;Faluyi, Y. O.;Tanner, C.;Mazoyer, B.;O'Neill, D.;Bartley, M.;Collins, D. R.;Coughlan, T.;Prvulovic, D.;Hampel, H.",2012,,10.1371/journal.pone.0032441,0,
2182,Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease,"The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa.",Aged;Alzheimer Disease/*pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/*pathology,"O'Dwyer, L.;Lamberton, F.;Bokde, A. L.;Ewers, M.;Faluyi, Y. O.;Tanner, C.;Mazoyer, B.;O'Neill, D.;Bartley, M.;Collins, D. R.;Coughlan, T.;Prvulovic, D.;Hampel, H.",2011,,10.1371/journal.pone.0021745,0,
2183,Using diffusion tensor imaging and mixed-effects models to investigate primary and secondary white matter degeneration in Alzheimer's disease and mild cognitive impairment,"White matter (WM) degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) may be a key indicator of early damage in AD. Here, we analyzed WM diffusion tensor data using Tract-Based Spatial Statistics in conjunction with mixed-effects models. Four indices of diffusion were assessed in 61 healthy control, 19 non-amnestic MCIs, 14 amnestic MCIs, and 9 AD patients. The aim of the study was to use advanced mixed-effects models to investigate the retrogenesis hypothesis of AD, which suggests that tracts that are late to myelinate in ontogenetic development are the earliest to be affected in AD. Our results show that a number of late-myelinating pathways, including the parahippocampal region and the inferior longitudinal fasciculus, were predominantly affected by changes in WM volume. Conversely, early-myelinating pathways were found to be affected by a combination of both WM and gray matter (GM) atrophy. A model of the entire WM structure of the brain returned GM models for two indices of diffusion, suggesting that more complex regional landscapes of diffusion lie hidden beneath a global analysis of the entire brain. Our results warn against an explanation of white matter damage that points simply to one of two mechanisms: secondary degeneration or direct damage of myelin. We suggest that tracts may be affected by both mechanisms, with the balance depending on whether tracts are early or late-myelinating. A greater understanding of the pattern of WM changes in AD may prove useful for the early detection of AD.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Diffusion Tensor Imaging/ methods;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted/ methods;Longitudinal Studies;Male;Mild Cognitive Impairment/ pathology;Models, Neurological;Nerve Degeneration/ pathology;Neuropsychological Tests","O'Dwyer, L.;Lamberton, F.;Bokde, A. L.;Ewers, M.;Faluyi, Y. O.;Tanner, C.;Mazoyer, B.;O'Neill, D.;Bartley, M.;Collins, D. R.;Coughlan, T.;Prvulovic, D.;Hampel, H.",2011,,10.3233/jad-2011-110137,0,
2184,Microstructural brain abnormalities in Huntington's disease: A two-year follow-up,"OBJECTIVES: To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging. EXPERIMENTAL DESIGN: From the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed. Age-corrected histograms of whole-brain white matter (WM), gray matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject's data set. PRINCIPLE OBSERVATIONS: Higher cross-sectional mean, axial and radial diffusivities were found in both WM (P </= 0.001) and GM (P </= 0.001) of the manifest HD compared to the preHD and control groups. In preHD, only WM axial diffusivity (AD) was higher than in controls (P </= 0.01). This finding remained valid only in preHD-B (P </= 0.001). AD was also higher in the striatum of preHD-B compared to controls and preHD-A (P </= 0.01). Fractional anisotropy (FA) lacked sensitivity in differentiating between the groups. Histogram peak heights were generally lower in manifest HD compared to the preHD and control groups. No longitudinal differences were found in the degree of diffusivity change between the groups in the two year follow-up. There was a significant relationship between diffusivity and neurocognitive measures. CONCLUSIONS: Alterations in cross-sectional diffusion profiles between manifest HD subjects and controls were evident, both in whole-brain and striatum. In the preHD stage, only AD alterations were found, a finding suggesting that this metric is a sensitive marker for early change in HD prior to disease manifestation. The individual diffusivities were superior to FA in revealing pathologic microstructural brain alterations. Diffusion measures were well related to clinical functioning and disease stage.",Adult;Anisotropy;Brain/ pathology;Diffusion Tensor Imaging;Female;Follow-Up Studies;Gray Matter/pathology;Humans;Huntington Disease/ pathology;Longitudinal Studies;Male;Middle Aged;White Matter/pathology,"Odish, O. F.;Leemans, A.;Reijntjes, R. H.;van den Bogaard, S. J.;Dumas, E. M.;Wolterbeek, R.;Tax, C. M.;Kuijf, H. J.;Vincken, K. L.;van der Grond, J.;Roos, R. A.",2015,Jun,10.1002/hbm.22756,0,
2185,Neurolymphomatosis associated with muscle and cerebral involvement caused by natural killer cell lymphoma: A case report and review of literature,"We report a biopsy-proven case of neurolymphomatosis (NL) presenting with sensory motor axonal polyneuropathy, polymyositis, and cerebral involvement. Ours is the second reported case of NL caused by natural killer-cell lymphoma defined by morphology and immunophenotyping. For 3 months, the patient developed stocking-glove distribution of hypesthesia, subacute progressive weakness and mental deterioration. EMG showed severe sensorimotor mixed axonal-demyelinating polyradiculoneuropathy. Lumbar puncture revealed mildly high protein level with normal glucose and cell count. Sural nerve biopsy demonstrated lymphomatous axonal neuropathy and muscle biopsy was indicative of lymphomatous polymyositis. Brain MRI revealed multiple white matter lesions, consistent either with progressive multifocal leukoencephalopathy or cerebral lymphoma. Bone marrow biopsy showed neoplastic infiltrates. The patient died of multiple organ failure prior to initiation of chemotherapy.",adult;article;case report;cerebrospinal fluid cytology;clinical feature;demyelination;electromyography;human;hypesthesia;immunophenotyping;lumbar puncture;lymphoma;lymphomatosis;male;mental deterioration;multiple organ failure;muscle biopsy;muscle weakness;natural killer cell;nerve biopsy;nuclear magnetic resonance imaging;polymyositis;polyneuropathy;polyradiculoneuropathy;priority journal;protein cerebrospinal fluid level;sensorimotor neuropathy;sural nerve;symptom,"Odabasi, Z.;Parrott, J. H.;Reddy, V. V. B.;Oh, S. J.",2001,,,0,
2186,Hemispatial visual defect in Alzheimer's disease,"We describe a 56-year-old woman with Alzheimer's disease with left hemispatial neglect and left homonymous hemianopsia with macular sparing considered a manifestation of Alzheimer's disease resulting from severe degenerative change in the right primary visual cortex. Hemispatial neglect normally results from brain damage to the right cerebral hemisphere. Homonymous hemianopsia is commonly the result of localized brain disease, especially cerebral infarction or hemorrhage. To our knowledge, a patient with Alzheimer's disease showing hemispatial neglect and homonymous hemianopsia with macular sparing has not previously been reported.",donepezil;adult;Alzheimer disease;anamnesis;article;brain atrophy;brain ischemia;case report;clinical feature;cognitive defect;drug treatment failure;female;hemispatial neglect;homonymous hemianopia;human;memory disorder;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;psychological rating scale;single photon emission computer tomography;visual acuity;visual disorder;visual system examination;Wechsler intelligence scale,"Oda, H.;Ohkawa, S.;Maeda, K.",2008,,,0,
2187,Comparison of Automated Brain Volume Measures obtained with NeuroQuant® and FreeSurfer,"PURPOSE: To examine intermethod reliabilities and differences between FreeSurfer and the FDA-cleared congener, NeuroQuant®, both fully automated methods for structural brain MRI measurements. MATERIALS AND METHODS: MRI scans from 20 normal control subjects, 20 Alzheimer's disease patients, and 20 mild traumatically brain-injured patients were analyzed with NeuroQuant® and with FreeSurfer. Intermethod reliability was evaluated. RESULTS: Pairwise correlation coefficients, intraclass correlation coefficients, and effect size differences were computed. NeuroQuant® versus FreeSurfer measures showed excellent to good intermethod reliability for the 21 regions evaluated (r: .63 to .99/ICC: .62 to .99/ES: -.33 to 2.08) except for the pallidum (r/ICC/ES = .31/.29/-2.2) and cerebellar white matter (r/ICC/ES = .31/.31/.08). Volumes reported by NeuroQuant were generally larger than those reported by FreeSurfer with the whole brain parenchyma volume reported by NeuroQuant 6.50% larger than the volume reported by FreeSurfer. There was no systematic difference in results between the 3 subgroups. CONCLUSION: NeuroQuant® and FreeSurfer showed good to excellent intermethod reliability in volumetric measurements for all brain regions examined with the only exceptions being the pallidum and cerebellar white matter. This finding was robust for normal individuals, patients with Alzheimer's disease, and patients with mild traumatic brain injury.",aged;Alzheimer disease;amygdaloid nucleus;article;automation;brain size;brain stem;caudate nucleus;cerebellum;cerebrospinal fluid;clinical article;comparative study;controlled study;correlation coefficient;diencephalon;effect size;female;forebrain;globus pallidus;gray matter;hippocampus;human;imaging software;lateral brain ventricle;male;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;putamen;reliability;thalamus;traumatic brain injury;white matter;FreeSurfer;NeuroQuant,"Ochs, A. L.;Ross, D. E.;Zannoni, M. D.;Abildskov, T. J.;Bigler, E. D.;For the Alzheimer's Disease Neuroimaging, Initiative",2015,,,0,
2188,Comparison of Automated Brain Volume Measures obtained with NeuroQuant and FreeSurfer,"PURPOSE: To examine intermethod reliabilities and differences between FreeSurfer and the FDA-cleared congener, NeuroQuant, both fully automated methods for structural brain MRI measurements. MATERIALS AND METHODS: MRI scans from 20 normal control subjects, 20 Alzheimer's disease patients, and 20 mild traumatically brain-injured patients were analyzed with NeuroQuant and with FreeSurfer. Intermethod reliability was evaluated. RESULTS: Pairwise correlation coefficients, intraclass correlation coefficients, and effect size differences were computed. NeuroQuant versus FreeSurfer measures showed excellent to good intermethod reliability for the 21 regions evaluated (r: .63 to .99/ICC: .62 to .99/ES: -.33 to 2.08) except for the pallidum (r/ICC/ES = .31/.29/-2.2) and cerebellar white matter (r/ICC/ES = .31/.31/.08). Volumes reported by NeuroQuant were generally larger than those reported by FreeSurfer with the whole brain parenchyma volume reported by NeuroQuant 6.50% larger than the volume reported by FreeSurfer. There was no systematic difference in results between the 3 subgroups. CONCLUSION: NeuroQuant and FreeSurfer showed good to excellent intermethod reliability in volumetric measurements for all brain regions examined with the only exceptions being the pallidum and cerebellar white matter. This finding was robust for normal individuals, patients with Alzheimer's disease, and patients with mild traumatic brain injury.",Brain morphometry;freesurfer;neuroquant(R);pallidum;reliability,"Ochs, A. L.;Ross, D. E.;Zannoni, M. D.;Abildskov, T. J.;Bigler, E. D.",2015,Sep-Oct,10.1111/jon.12229,0,
2189,A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET,"We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-1 antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We invesigated cerebral blood flow, glucose and amino acid metabolism in this patient using position emission tomography, and obtained the following three characteristic findings in the lessions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.",fluorodeoxyglucose;Human T cell leukemia virus antigen;methionine;adult;article;case report;diagnostic accuracy;diagnostic value;histopathology;human;human cell;human tissue;image analysis;JC virus;leukoencephalopathy;male;nuclear magnetic resonance imaging;oligodendroglia;T cell leukemia,"Ochi, H.;Yamada, T.;Hara, H.;Yoshimura, T.;Iwaki, T.;Nagashima, K.;Yogo, Y.;Kobayashi, T.",1996,,,0,
2190,Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases,"Generalised ventricular dilatation with or without cerebral atrophy is common in longstanding multiple sclerosis. This has been widely assumed to be due to periventricular white matter atrophy rather than true communicating hydrocephalus although it can be difficult to distinguish between these on radiological grounds. Here we report 2 chronic MS patients who had progressive dementia, gait disturbance and urinary incontinence and in whom neuroimaging, and in one case CSF infusion studies, suggested hydrocephalus. Both significantly improved following shunting procedures. We suggest that further study is required to investigate whether a significant proportion of patients with chronic MS and dilated ventricles have shunt-responsive hydrocephalus.",article;case report;cerebrospinal fluid shunting;chronic disease;human;hydrocephalus;male;middle aged;multiple sclerosis;nuclear magnetic resonance imaging,"O'Brien, T.;Paine, M.;Matotek, K.;Byrne, E.",1993,,,0,
2191,"Vascular dementia: Atherosclerosis, cognition and alzheimer's disease","Both Alzheimer's disease type pathology (neuritic plaques and neurofibrillary tangles) and evidence of atherosclerosis and infarcts are common in autopsy specimens from the brains of patients enrolled in longitudinal prospective cohorts; the relative contribution of each of these to overall cognitive function is unclear. In addition whether each of these two forms of brain pathology can accelerate the appearance of the other is also unclear. In this paper we examine the relationship among Alzheimer's brain pathology, cerebral infarcts and cerebral atherosclerosis. We conclude that each is an independent predictor of dementia. Moreover we do not find that atherosclerosis increases Alzheimer's type brain pathology or vice versa. © 2011 Bentham Science Publishers Ltd.",Alzheimer disease;article;autopsy;blood brain barrier;brain atherosclerosis;brain circulus arteriosus;brain disease;brain infarction;cardiovascular risk;cognition;cognitive reserve;computer assisted tomography;disease association;human;multiinfarct dementia;nerve cell plasticity;neurofibrillary tangle;nuclear magnetic resonance imaging;prediction;priority journal;senile plaque;cerebrovascular accident;white matter;white matter disease,"Obrien, R. J.",2011,,,0,
2192,Magnetic resonance imaging correlates of memory impairment in the healthy elderly: association with medial temporal lobe atrophy but not white matter lesions,"OBJECTIVE: To investigate the neuroradiological correlates of age-related cognitive decline in the elderly. DESIGN: A sample of healthy control subjects underwent magnetic resonance imaging (MRI) scanning and cognitive testing. SETTING: Melbourne, Australia. PARTICIPANTS: 40 volunteers over the age of 55 who were spouses of subjects seen in a hospital memory clinic, subjects from a register of normal volunteer subjects (not staff) kept for research purposes or residents of a retirement hostel. MEASURES: Hippocampal and amygdala (HA) atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: After controlling for age and education, lower scores on the memory subscale of the CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL. CONCLUSIONS: HA atrophy on MRI is associated with impaired memory performance in the healthy elderly, while PVL and DWML are not. Further study should determine whether HA atrophy is a risk factor for developing dementia.","Aged;Aged, 80 and over;Amygdala/pathology;Atrophy;Brain/pathology;Cerebral Ventricles/pathology;Dementia/ diagnosis;Dementia, Vascular/diagnosis;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Mental Recall/ physiology;Middle Aged;Neuropsychological Tests;Reference Values;Temporal Lobe/ pathology","O'Brien, J. T.;Desmond, P.;Ames, D.;Schweitzer, I.;Tress, B.",1997,Mar,,0,
2193,"Clinical, magnetic resonance imaging and endocrinological differences between delusional and non-delusional depression in the elderly","OBJECTIVE: To investigate neuroradiological, endocrinological and clinical differences between delusional and non-delusional depression. DESIGN: A cross-sectional study of depressed subjects. SETTING: Melbourne, Australia. PARTICIPANTS: Sixty-one subjects (inpatients) over the age of 55 meeting DSM-III-R criteria for major depression of whom 22 had delusional subtype of depression. MEASURES: Clinical assessment, including documentation of vascular risk factors. Cognitive assessment by the Cambridge Cognitive Examination (CAMCOG). Magnetic resonance imaging (MRI) scans were performed on a 0.3 Tesla scanner with temporal lobe atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) rated visually on 4-point scales. A standard 1 mg dexamethasone suppression test (DST) was performed. RESULTS: Subjects with delusional depression had significantly more vascular risk factors than those without delusions. There were no differences in measures of temporal lobe atrophy, PVL, DST results or cognitive test scores, though there was a non-significant trend for DWML to be more prevalent in those with delusions. Delusional depression was associated with a shorter duration of history and more frequent treatment with ECT. CONCLUSIONS: The increase in vascular risk factors and trend towards greater DWML on MRI suggests an organic contribution to delusional depression in the elderly. In contrast to some previous reports, we found no differences in cortical MRI appearance or neuroendocrine measures between groups.","Aged;Aged, 80 and over;Brain/ pathology;Delusions/ diagnosis;Dementia/blood/ diagnosis/psychology;Dementia, Vascular/diagnosis;Depressive Disorder/blood/ diagnosis/psychology;Dexamethasone;Female;Humans;Hydrocortisone/ blood;Magnetic Resonance Imaging;Male;Psychiatric Status Rating Scales;Risk Factors","O'Brien, J. T.;Ames, D.;Schweitzer, I.;Desmond, P.;Coleman, P.;Tress, B.",1997,Feb,,0,
2194,White matter lesions in depression and Alzheimer's disease,,"Alzheimer Disease/*diagnosis/psychology;Brain/*pathology;Cerebrovascular Disorders/diagnosis/psychology;Depressive Disorder/*diagnosis/psychology;Humans;Ischemic Attack, Transient/diagnosis/psychology;*Magnetic Resonance Imaging","O'Brien, J. T.;Ames, D.",1996,Nov,,0,
2195,The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms,"A number of studies have suggested that cerebral changes, particularly deep white matter lesions (WML) visualized on magnetic resonance imaging (MRI), may be involved in the genesis of late life depression. This has been confirmed in a prospective study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects. Most studies find these lesions to predominate in frontal lobe and basal ganglia, supporting the hypothesis of ""fronto-striatal"" dysfunction in depression. To investigate whether WML are associated with mood disturbance in dementia, proton density and T2-weighted images were obtained in 80 subjects with dementia (dementia with Lewy bodies, n = 27; Alzheimer's disease, n = 28; vascular dementia, n = 25) and 26 age-matched normal controls. Periventricular lesions (PVL), white matter lesions (WML), and basal ganglia hyperintensities (BG) were visually rated blind to diagnosis using a semiquantitative scale. Frontal WML were associated with higher depression scores in patients with dementia, implying a common pathophysiology of depression irrespective of diagnosis. Further study of the neurobiological basis of WML is needed. This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination.","Aged;Alzheimer Disease/ pathology/psychology;Brain/anatomy & histology/ pathology;Dementia, Vascular/ pathology/psychology;Depression/pathology;Female;Humans;Lewy Body Disease/ pathology/psychology;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Reference Values","O'Brien, J.;Perry, R.;Barber, R.;Gholkar, A.;Thomas, A.",2000,Apr,,0,
2196,A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease,"BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/psychology;Brain/ pathology;Brain Damage, Chronic/diagnosis/psychology;Cerebral Infarction/diagnosis/psychology;Cerebral Ventricles/pathology;Depressive Disorder/ diagnosis/psychology;Female;Humans;Intracranial Arteriosclerosis/diagnosis/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neurocognitive Disorders/ diagnosis/psychology;Neuropsychological Tests/statistics & numerical data;Observer Variation;Personality Inventory/statistics & numerical data;Psychometrics","O'Brien, J.;Desmond, P.;Ames, D.;Schweitzer, I.;Harrigan, S.;Tress, B.",1996,Apr,,0,
2197,A case of Creutzfeldt-Jakob disease (CJD) started with monoparesis of the left arm,"A 72-year-old man developed a sudden weakness in his left hand on October 5, 1991. He was admitted two weeks thereafter. Physical examination revealed minimal weakness, and clumsiness of the fingers on his left hand. Exaggerated tendon reflexes and spasticity were also noted only on his left upper limb. He had neither dementia nor psychiatric symptoms. Subsequently he developed weakness in his left leg on November 17. Within 12 days he developed left facial weakness and myoclonic movements on the left side. By December 2, he developed spastic tetraparesis with bilateral facial palsy, and generalized myoclonic jerks. A few days after that he started to show decorticate posture. From December 16, his mental status deteriorated rapidly, and he became mute, and uncooperative within a week. His clinical course can be summarized as stepwise progression similar to a cerebrovascular accident. Electroencephalography was normal on admission, but periodic synchronous discharge developed in January 1992. Brain CT that showed only mild brain atrophy at first was considered to be compatible with his age, changed to have severe brain atrophy in March 1992. He died of pneumonia on May 24, 1992 after eight months of progressive clinical course. Autopsy was done. The brain weighed 930 grams. Macroscopically there was prominent cortical atrophy. Microscopic examination revealed severe spongy state throughout the cerebral cortex. Typical spongiform changes were confined to the hippocampus. The cerebral white matter appeared to be normal. In the cerebellar cortex, the granular cell layer disappeared and Purkinje's cell were reduced in number. Kuru plaques were not seen. The cerebellar white matter, dentate nucleus, and brainstem seemed to be normal. The spinal cord was not examined. There were no pathological changes to indicate cerebrovascular accident, except for a lacuna in the right basal ganglion and a small angionecrosis in the pons. Western blotting test using Anti-APC (amyloid plaque core) antibody was positive. Neuropathological changes of the present case were consistent with those of CJD. However, the sudden onset of monoparesis without dementia or ataxia is rare as the initial symptom of this disease. The subsequent clinical course with stepwise progression of hemiplegia, which was mimicking a progressive stroke, was also rare for CJD. In comparison to typical case of CJD, this case had a different clinical onset as acute monoparesis. We can find such cases of CJD presenting as stroke in 5.6% in the previous English literatures.",aged;arm muscle;article;autopsy;case report;computer assisted tomography;Creutzfeldt Jakob disease;differential diagnosis;disease course;electroencephalogram;histopathology;human;human cell;human tissue;male;muscle weakness,"Obi, T.;Takatsu, M.;Kitamoto, T.;Mizoguchi, K.;Nishimura, Y.",1996,,,0,
2198,[The characteristics of a comprehensive geriatric assessment in patients with mild cognitive impairment with a cerebral white matter lesion],"AIM: Vascular dementia may be referred to as ""treatable dementia"" because its development and progress can be inhibited by intervention in the early stage. In particular, cerebral white matter lesions are readily encountered the clinical setting. In this study, we aimed to clarify the phenomenon and symptoms of patients with mild cognitive impairment (MCI) with cerebral white matter lesions prior to the onset of dementia. METHODS: The subjects included 181 cases diagnosed with MCI among 643 consecutive new patients of the Center for Comprehensive Care on Memory Disorder at Kyorin University Hospital from January 1, 2013 to January 31, 2014. Patients with particular diseases were excluded. An interview, physical examination, comprehensive geriatric assessment, brain MRI and SPECT were performed for all subjects. The cerebral white matter lesions were evaluated using the modified Fazekas scale. We defined Grades 0 and 1 as the group without apparent cerebral white matter lesions and Grades 2 and 3 as the group with apparent cerebral white matter lesions. We compared the laboratory findings and outcomes of these two groups. RESULTS: The age of the group with apparent cerebral white matter lesions was significantly higher than the group without apparent cerebral white matter lesions (P<0.05). No significant difference was observed regarding gender, MMSE, or ""vegetable"" term retrieval. A significant difference was observed in the total score and the subordinate component of the 21-item fall risk index and geriatric depression scale between the groups (P<0.05). Additionally, a significant difference was observed regarding the subordinate component of the instrumental ADL, the Dementia Behavior Disturbance Scale and the Zarit Care Burden Scale between the groups (P<0.05). CONCLUSIONS: Our results suggest that the presence of white matter lesions at the stage of MCI has a significant relationship to care burden due to the deterioration of ADL, risk of falling, and the presence of depression and behavior disorders. We speculate that our results are useful for the explanation of the characteristics of MCI with white matter lesion to the patients and the care givers. Furthermore, these results may lead to improvements in the appropriate approach, intervention and appropriate nursing of such patients.",,"Obara, T.;Hasegawa, H.;Wachi, Y.;Tanaka, M.;Sato, M.;Kobayashi, Y.;Koshiba, H.;Nagai, K.;Yamada, Y.;Matsui, T.;Kozaki, K.",2015,,10.3143/geriatrics.52.399,0,
2199,Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type,"Cerebral CT changes are correlated with cognitive declines among 18 patients with probable dementia of Alzheimer type (DAT) (7 men, 11 women, mean age 75.4 years) and are compared for control purposes with similar measures among 18 age-matched normal volunteers (8 men, 10 women, mean age 73.7 years). Mean follow-up intervals are 28.6 months for DAT and 27.0 months for controls. For DAT, annual rates for ventricular volume enlargement are +9.2% and for cortical atrophy are -2.1%. Annual reductions in regional cerebral perfusions per 100 g brain/min, are: total cortex -1.1 ml, frontal -1.2 ml, temporal and parietal -0.9 ml, basal ganglia -1.6 ml, thalamus -2.5 ml, total white matter -0.6 ml, frontal white matter -0.7 ml. At entry evaluation, compared to normals, DAT patients had reduced CT densities in white matter, but not in cortex. Nevertheless, cortical CT densities declined progressively at annual rates of -0.72 Hounsfield units (HU), but remained constant in white matter. Annual point score declines for Cognitive Capacity Screening Examinations were -2.0 and for Mini Mental State: -2.8. Controls showed no cognitive change. Multiple regression analyses correlate cognitive declines with: (1) reductions in perfusion within parietal cortex (p = 0.015), (2) decreases in cortical volume (p = 0.019), and (3) decreases in HU within subcortical gray matter (p = 0.007).","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/*psychology;Brain/blood supply/*pathology/radiography;*Cerebrovascular Circulation;Cognition Disorders/*etiology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Neuropsychological Tests;Severity of Illness Index;Tomography, X-Ray Computed","Obara, K.;Meyer, J. S.;Mortel, K. F.;Muramatsu, K.",1994,Dec 1,,0,
2200,The APOE epsilon4 allele in relation to brain white-matter microstructure in adulthood and aging,"The Apolipoprotein E (ApoE) epsilon4 allele is a major genetic risk factor for sporadic Alzheimer's disease and has been associated with structural and functional brain alterations across the adult life span. Recent studies have presented evidence that epsilon4 affects microstructural properties of brain white matter (WM) in non-demented carriers of the epsilon4 allele, but conflicting evidence has been presented as well. The main purpose of the present study was therefore to examine ApoE effects on WM in a large sample of middle-aged and older adults (N = 273). Diffusion tensor imaging (DTI) data was acquired, and tract-based as well as voxel-wise analyses were conducted. The tract-based analyses revealed no significant ApoE effects, and no significant interactions between genotype and age were observed. Taken together, the findings of the present study suggest that ApoE effects on white-matter microstructure are less abundant than has been suggested in some previous studies.","Aged;Aged, 80 and over;Aging/ genetics/ pathology;Alleles;Apolipoprotein E4/ genetics;Diffusion Tensor Imaging/ methods;Humans;Male;Middle Aged;Prospective Studies;White Matter/ pathology","Nyberg, L.;Salami, A.",2014,Jun,10.1111/sjop.12099,0,
2201,Functional brain imaging of episodic memory decline in ageing,"The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation.",adult;aging;amnesia;blood oxygenation;BOLD signal;brain cortex;clinical study;dementia;episodic memory;functional magnetic resonance imaging;functional neuroimaging;glucose metabolism;hippocampus;human;human tissue;long term memory;neurotransmission;positron emission tomography;rest;stimulation;white matter;amyloid beta protein,"Nyberg, L.",2016,,,0,
2202,Cigarette Smoke-Induced Alterations in Frontal White Matter Lipid Profiles Demonstrated by MALDI-Imaging Mass Spectrometry: Relevance to Alzheimer's Disease,"BACKGROUND: Meta-analysis has shown that smokers have significantly increased risks for Alzheimer's disease (AD), and neuroimaging studies showed that smoking alters white matter (WM) structural integrity. OBJECTIVE: Herein, we characterize the effects of cigarette smoke (CS) exposures and withdrawal on WM myelin lipid composition using matrix assisted laser desorption and ionization-imaging mass spectrometry (MALDI-IMS). METHODS: Young adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). Frontal lobe WM was examined for indices of lipid and protein oxidation and lipid profile alterations by MALDI-IMS. Lipid ions were identified by MS/MS with the LIPID MAPS prediction tools database. Inter-group comparisons were made using principal component analysis and R-generated heatmap. RESULTS: CS increased lipid and protein adducts such that higher levels were present in CS8 compared with CS4 samples. CS8 + R reversed CS8 effects and normalized the levels of oxidative stress. MALDI-IMS demonstrated striking CS-associated alterations in WM lipid profiles characterized by either reductions or increases in phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidylcholine, or phosphatidylethanolamine) and sphingolipids (sulfatides), and partial reversal of CS's inhibitory effects with recovery. The heatmap hierarchical dendrogram and PCA distinguished CS exposure, duration, and withdrawal effects on WM lipid profiles. CONCLUSION: CS-mediated WM degeneration is associated with lipid peroxidation, protein oxidative injury, and alterations in myelin lipid composition, including shifts in phospholipids and sphingolipids needed for membrane integrity, plasticity, and intracellular signaling. Future goals are to delineate WM abnormalities in AD using MALDI-IMS, and couple the findings with MRI-mass spectroscopy to improve in vivo diagnostics and early detection of brain biochemical responses to treatment.",,"Nunez, K.;Kay, J.;Krotow, A.;Tong, M.;Agarwal, A. R.;Cadenas, E.;de la Monte, S. M.",2016,Jan 20,10.3233/jad-150916,0,
2203,Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?,"Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to-(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14 % lower CMRg (mumol/100 g/min) specifically in the frontal cortex, and 18 % lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.",Aging;Brain;Cognition;Energy metabolism;Glucose;Mri;Positron emission tomography,"Nugent, S.;Castellano, C. A.;Bocti, C.;Dionne, I.;Fulop, T.;Cunnane, S. C.",2016,Feb,10.1007/s10522-015-9595-7,0,
2204,The fornix in mild cognitive impairment and Alzheimer's disease,"The fornix is an integral white matter bundle located in the medial diencephalon and is part of the limbic structures. It serves a vital role in memory functions and as such has become the subject of recent research emphasis in Alzheimer's disease (AD) and mild cognitive impairment (MCI). As the characteristic pathological processes of AD progress, structural and functional changes to the medial temporal lobes and other regions become evident years before clinical symptoms are present. Though gray matter atrophy has been the most studied, degradation of white matter structures especially the fornix may precede these and has become detectable with use of diffusion tensor imaging (DTI) and other complimentary imaging techniques. Recent research utilizing DTI measurement of the fornix has shown good discriminability of diagnostic groups, particularly early and preclinical, as well as predictive power for incident MCI and AD. Stimulating and modulating fornix function by the way of DBS has been an exciting new area as pharmacological therapeutics has been slow to develop.",,"Nowrangi, M. A.;Rosenberg, P. B.",2015,,,0,
2205,Atlas-based diffusion tensor imaging correlates of executive function,"Impairment in executive function (EF) is commonly found in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Atlas-based diffusion tensor imaging (DTI) methods may be useful in relating regional integrity to EF measures in MCI and AD. Sixty-six participants (25 normal controls, 22 MCI, and 19 AD) received DTI scans and clinical evaluation. DTI scans were applied to a pre-segmented atlas and fractional anisotropy (FA) and mean diffusivity (MD) were calculated. ANOVA was used to assess group differences in frontal, parietal, and cerebellar regions. For regions differing between groups (p < 0.01), linear regression examined the relationship between EF scores and regional FA and MD. Anisotropy and diffusivity in frontal and parietal lobe white matter structures were associated with EF scores in MCI and only frontal lobe structures in AD. EF was more strongly associated with FA than MD. The relationship between EF and anisotropy and diffusivity was strongest in MCI. These results suggest that regional white matter integrity is compromised in MCI and AD and that FA may be a better correlate of EF than MD.",Aged;Alzheimer Disease/ pathology/ psychology;Anisotropy;Atlases as Topic;Brain/ pathology;Diffusion Tensor Imaging/methods;Executive Function;Female;Humans;Male;Mild Cognitive Impairment/ pathology/ psychology;Neuropsychological Tests,"Nowrangi, M. A.;Okonkwo, O.;Lyketsos, C.;Oishi, K.;Mori, S.;Albert, M.;Mielke, M. M.",2015,,10.3233/jad-141937,0,
2206,"Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer's disease","BACKGROUND: Diffusion tensor imaging (DTI) is a promising method for identifying significant cross-sectional differences of white-matter tracts in normal controls (NC) and those with mild cognitive impairment (MCI) or Alzheimer's disease (AD). There have not been many studies establishing its longitudinal utility. METHODS: Seventy-five participants (25 NC, 25 amnestic MCI, and 25 AD) had 3-Tesla MRI scans and clinical evaluations at baseline and 3, 6, and 12 months. Fractional anisotropy (FA) and mean diffusivity (MD) were analyzed at each time-point and longitudinally in eight a priori-selected areas taken from four regions of interest (ROIs). RESULTS: Cross-sectionally, MD values were higher, and FA values lower in the fornix and splenium of the AD group compared with either MCI or NC (P < .01). Within-group change was more evident in MD than in FA over 12 months: MD increased in the inferior, anterior cingulum, and fornix in both the MCI and AD groups (P < .01). CONCLUSIONS: There were stable, cross-sectional, region-specific differences between the NC and AD groups in both FA and MD at each time-point over 12 months. Longitudinally, MD was a better indicator of change than FA. Significant increases of fornix MD in the MCI group suggest this is an early indicator of progression.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Interpretation, Computer-Assisted;Longitudinal Studies;Male;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology","Nowrangi, M. A.;Lyketsos, C. G.;Leoutsakos, J. M.;Oishi, K.;Albert, M.;Mori, S.;Mielke, M. M.",2013,Sep,10.1016/j.jalz.2012.05.2186,0,
2207,Basal ganglia-cortical structural connectivity in Huntington's disease,"Huntington's disease is an incurable neurodegenerative disease caused by inheritance of an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat within the Huntingtin gene. Extensive volume loss and altered diffusion metrics in the basal ganglia, cortex and white matter are seen when patients with Huntington's disease (HD) undergo structural imaging, suggesting that changes in basal ganglia-cortical structural connectivity occur. The aims of this study were to characterise altered patterns of basal ganglia-cortical structural connectivity with high anatomical precision in premanifest and early manifest HD, and to identify associations between structural connectivity and genetic or clinical markers of HD. 3-Tesla diffusion tensor magnetic resonance images were acquired from 14 early manifest HD subjects, 17 premanifest HD subjects and 18 controls. Voxel-based analyses of probabilistic tractography were used to quantify basal ganglia-cortical structural connections. Canonical variate analysis was used to demonstrate disease-associated patterns of altered connectivity and to test for associations between connectivity and genetic and clinical markers of HD; this is the first study in which such analyses have been used. Widespread changes were seen in basal ganglia-cortical structural connectivity in early manifest HD subjects; this has relevance for development of therapies targeting the striatum. Premanifest HD subjects had a pattern of connectivity more similar to that of controls, suggesting progressive change in connections over time. Associations between structural connectivity patterns and motor and cognitive markers of disease severity were present in early manifest subjects. Our data suggest the clinical phenotype in manifest HD may be at least partly a result of altered connectivity.","Adult;Basal Ganglia/ pathology;Corpus Striatum/ pathology;Female;Humans;Huntington Disease/genetics/ pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology;Severity of Illness Index;Trinucleotide Repeat Expansion","Novak, M. J.;Seunarine, K. K.;Gibbard, C. R.;McColgan, P.;Draganski, B.;Friston, K.;Clark, C. A.;Tabrizi, S. J.",2015,May,10.1002/hbm.22733,0,
2208,White matter integrity in premanifest and early Huntington's disease is related to caudate loss and disease progression,"INTRODUCTION: Huntington's disease (HD) is associated with progressive loss of caudate and white matter volume and integrity. Our aim was to systematically assess interactions between these changes and genetic markers of disease progression; we are not aware of previous studies in which this has been explicitly tested. METHODS: Tract-based spatial statistics were used to assess: (a) differences between the white matter diffusion metrics (fractional anisotropy and mean diffusivity) of 17 premanifest and 19 early manifest HD gene carriers and 21 controls, and (b) the relationships between diffusion metrics, caudate and total white matter volume, and disease burden score and CAG repeat length. Caudate and total white matter volumes were quantified using FIRST and SIENAX respectively. Multiple regression analysis was used to assess which of the imaging metrics predicted disease severity in the HD subjects. RESULTS: Diffusion metrics were significantly altered in premanifest and early HD gene carriers in comparison with controls throughout the white matter skeleton. Correlations between diffusion and volumetric metrics and disease progression were also present. Together, caudate volume and mean white matter fractional anisotropy and mean diffusivity predicted disease burden score in the HD subjects. CONCLUSIONS: The diffusion properties of white matter are extensively altered in HD, and are associated with markers of HD severity, and with caudate and white matter volumes. The correlation between diffusion metrics and white matter volume is stronger in HD subjects than in controls, but there is no such significant interaction for the correlation between diffusion and caudate volume: we propose that many of the changes in white matter diffusion in HD occur as a 'normal' physiological response to pathological caudate volume loss. We have defined the extent to which mean white matter fractional anisotropy, white matter volume and caudate volume are associated with disease burden score.","Adult;Atrophy/pathology;Caudate Nucleus/ pathology;Disease Progression;Female;Humans;Huntington Disease/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuroimaging;Organ Size","Novak, M. J.;Seunarine, K. K.;Gibbard, C. R.;Hobbs, N. Z.;Scahill, R. I.;Clark, C. A.;Tabrizi, S. J.",2014,Mar,10.1016/j.cortex.2013.11.009,0,
2209,Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes,"AIMS/HYPOTHESES: In adults, type 2 diabetes and obesity have been associated with structural brain changes, even in the absence of dementia. Some evidence suggested similar changes in adolescents with type 2 diabetes but comparisons with a non-obese control group have been lacking. The aim of the current study was to examine differences in microstructure of gray and white matter between adolescents with type 2 diabetes, obese adolescents and healthy weight adolescents. METHODS: Magnetic resonance imaging data were collected from 15 adolescents with type 2 diabetes, 21 obese adolescents and 22 healthy weight controls. Volumetric differences in the gray matter between the three groups were examined using voxel based morphology, while tract based spatial statistics was used to examine differences in the microstructure of the white matter. RESULTS: Adolescents with type 2 diabetes and obese adolescents had reduced gray matter volume in the right hippocampus, left putamen and caudate, bilateral amygdala and left thalamus compared to healthy weight controls. Type 2 diabetes was also associated with significant regional changes in fractional anisotropy within the corpus callosum, fornix, left inferior fronto-occipital fasciculus, left uncinate, left internal and external capsule. Fractional anisotropy reductions within these tracts were explained by increased radial diffusivity, which may suggest demyelination of white matter tracts. Mean diffusivity and axial diffusivity did not differ between the groups. CONCLUSION/INTERPRETATION: Our data shows that adolescent obesity alone results in reduced gray matter volume and that adolescent type 2 diabetes is associated with both white and gray matter abnormalities.","Demyelination;Gray matter;HbA1c, Haemoglobin A1c;Obesity;Type 2 diabetes;White matter","Nouwen, A.;Chambers, A.;Chechlacz, M.;Higgs, S.;Blissett, J.;Barrett, T. G.;Allen, H. A.",2017,,,0,
2210,"[Late-onset depression : Pathophysiology, diagnostics and treatment]","Late-onset depression (LOD) is defined as depression manifesting for the first time in later life. Up to now, there has been no exact definition of the lower age limit for LOD. Psychopathological symptoms of LOD do not fundamentally differ from depression in other phases of life; however, cognitive deficits are typically more pronounced. The LOD is associated with an increased risk of developing dementia. Imaging studies show reduction in gray matter volume and white matter lesions caused by vascular diseases. The occurrence of depression with vascular lesions of the brain is also referred to as ""vascular depression"". The diagnostic procedure includes a detailed medical history and the observation of psychopathological changes, physical examination, laboratory tests, electroencephalograph (EEG), electrocardiograph (ECG) and magnetic resonance imaging (MRI) of the head and neuropsychological tests to measure cognitive deficits. Psychotherapy is an effective treatment option. Selective serotonin reuptake inhibitors are the first-line pharmacological therapy.",Dementia;Electroconvulsive therapy;Lithium;Treatment resistance;Vascular depression,"Notzon, S.;Alferink, J.;Arolt, V.",2016,Sep,10.1007/s00115-016-0193-y,0,
2211,Variables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment,"The goal of this study was to identify factors contributing to hippocampal atrophy rate (HAR) in clinically normal older adults (NC) and participants with mild cognitive impairment (MCI). Longitudinal HAR was measured on T1-weighted magnetic resonance imaging, and the contribution of age, gender, apolipoprotein E (ApoE) ε4 status, intracranial volume, white matter lesions, and β-amyloid (Aβ) levels to HAR was determined using linear regression. Age-related effects of HAR were compared in Aβ positive (Aβ+) and Aβ negative (Aβ-) participants. Age and Aβ levels had independent effects on HAR in NC, whereas gender, ApoE ε4 status, and Aβ levels were associated with HAR in MCI. In multivariable models, Aβ levels were associated with HAR in NC; ApoE ε4 and Aβ levels were associated with HAR in MCI. In MCI, age was a stronger predictor of HAR in Aβ- versus Aβ+ participants. HAR was higher in Aβ+ participants, but most of the HAR was because of factors other than Aβ status. Age-related effects on HAR did not differ between NC versus MCI participants with the same Aβ status. Therefore, we conclude that even when accounting for other covariates, Aβ status, and not age, is a significant predictor of HAR; and that most of the HAR is not accounted for by Aβ status in either NC or MCI. © 2014 Elsevier Inc. All rights reserved.",,"Nosheny, R. L.;Insel, P. S.;Truran, D.;Schuff, N.;Jack Jr, C. R.;Aisen, P. S.;Shaw, L. M.;Trojanowski, J. Q.;Weiner, M. W.",2014,,,0,
2212,Subjective cognitive failures and hippocampal volume in elderly with white matter lesions,"BACKGROUND: Subjective cognitive failures (SCF) and subjective memory failures (SMF) have been reported to be an early predictor of Alzheimer disease (AD) and have been attributed to white matter lesions (WML). Since AD is characterized by hippocampal degeneration, it is surprising that its relation with hippocampal atrophy has been investigated only sparsely. Previous studies on this are rare, limited in sample size, and did not adjust for WML. OBJECTIVE: To determine the relation between SCF and hippocampal volume in strata of objective cognitive performance among elderly without dementia with incidental WML. METHODS: The Radboud University Nijmegen Diffusion tensor and MRI Cohort study is a prospective cohort study among 503 subjects with WML aged between 50 and 85 years. All subjects underwent FLAIR and T1 MRI scanning. The amount of SCF and SMF was rated by the Cognitive Failure Questionnaire. Cognitive function was assessed by a cognitive screening battery. Volumetric measures of hippocampus and WML were manually performed. We assessed the relation between hippocampal volume and SCF and SMF adjusted for age, sex, education, depression, intracranial volume, and WML volume. RESULTS: Subjects with SCF and SMF had lower hippocampal volumes than those without (p = 0.01 and p = 0.02). This was most noteworthy in subjects with good objective cognitive performance (p(trend) = 0.007 and p(trend) = 0.03), and not in those with poor objective cognitive performance. CONCLUSION: Subjective cognitive failures (SCF) are associated with lower hippocampal volume, even in subjects without objective cognitive impairment and independent of white matter lesions. SCF has a radiologic detectable pathologic-anatomic substrate.","Alzheimer Disease [epidemiology];Atrophy;Cognition Disorders [epidemiology] [pathology];Diffusion Magnetic Resonance Imaging;Hippocampus [pathology];Memory Disorders [epidemiology] [pathology];Nerve Fibers, Myelinated [pathology];Neuropsychological Tests;Prospective Studies;Risk Factors;Severity of Illness Index;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Norden, A. G.;Fick, W. F.;Laat, K. F.;Uden, I. W.;Oudheusden, L. J.;Tendolkar, I.;Zwiers, M. P.;Leeuw, F. E.",2008,,10.1212/01.wnl.0000327564.44819.49,0,
2213,Different mechanisms of episodic memory failure in mild cognitive impairment,"Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.","Aged;Aged, 80 and over;Analysis of Variance;Atrophy/pathology/physiopathology;Brain/pathology/physiopathology;Brain Diseases;Brain Mapping;Cognition Disorders/pathology/*physiopathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Memory Disorders/pathology/*physiopathology;Memory, Short-Term/*physiology;Neuropsychological Tests/statistics & numerical data;Space Perception/physiology;Verbal Behavior/physiology","Nordahl, C. W.;Ranganath, C.;Yonelinas, A. P.;DeCarli, C.;Reed, B. R.;Jagust, W. J.",2005,,10.1016/j.neuropsychologia.2005.01.003,0,
2214,Cerebral cortex structure in prodromal Huntington disease,"Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is ""spared,"" despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as ""Far from onset,"" ""Midway to onset,"" ""Near onset,"" and ""already diagnosed."" MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum.",Adult;Cerebral Cortex/*pathology;Early Diagnosis;Female;Humans;Huntington Disease/genetics/*pathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged,"Nopoulos, P. C.;Aylward, E. H.;Ross, C. A.;Johnson, H. J.;Magnotta, V. A.;Juhl, A. R.;Pierson, R. K.;Mills, J.;Langbehn, D. R.;Paulsen, J. S.",2010,Dec,10.1016/j.nbd.2010.07.014,0,
2215,Scoliosis in a patient with Alexander disease,"Alexander disease is a rare, degenerative disorder of the central nervous system. It is characterized clinically by spasticity, seizures, dementia, loss of developmental milestones, and macrocephaly. Here we describe a 13-year-old boy with Alexander disease and severe scoliosis. The patient initially presented at 9 months of age, with profound mental retardation and a history of seizures. When he was 7 years old, a pediatrician had diagnosed Alexander disease (hypotonia, macrocephaly, and progressive low-density white matter predominantly in the frontal region on computed tomography examination). From the age of 10, thoracolumbar scoliosis had gradually become severe. Because treatment using a corrective brace would have produced major problems because of the patient's mental retardation, the scoliosis was successfully treated surgically, by careful posterior spinal fusion with instrumentation, and an autologous iliac crest bone graft. A 64° curve was corrected to 18° (72% correction). Scoliosis with Alexander disease is considered to be very rare because patients with the disease seldom survive long enough to develop spinal deformities. © 2002 Lippincott Williams & Wilkins, Inc.",Alexander disease;anamnesis;article;bone graft;case report;computer assisted tomography;electroencephalogram;human;infant;devices;male;mental deficiency;priority journal;rare disease;scoliosis;spine fusion;symptomatology;X ray,"Nonomura, Y.;Shimizu, K.;Nishimoto, H.;Hosoe, H.;Sakaguchi, Y.;Miyamoto, K.",2002,,,0,
2216,Pre-critical MRI findings of an Alzheimer's disease patient with pathologically proven cerebral amyloid angiopathy related lobar hemorrhage,"An 85-year-old woman with untreated hypertension was admitted with a disturbance of consciousness. On admission, brain CT revealed a lobar intracerebral hemorrhage with a midline shift. An intracranial hematoma was evacuated via a life-saving craniotomy. Definite pathological findings of amyloid-beta deposition in the excised hematoma (strong in anti-amyloid beta40 immunostain, but weak in anti- amyloid beta42) indicated cerebral amyloid angiopathy (CAA). She had been diagnosed with Alzheimer's disease at a regional memory clinic one month before symptom onset based on MRI findings of medial temporal lobe atrophy as well as CAA-related features of multiple strictly lobar cerebral microbleeds in the occipital lobe, cortical superficial siderosis and >20 enlarged perivascular spaces in the centrum semiovale. This experience suggests that comprehensive interpretation of such CAA-related findings on MRI might help to improve the management of cardiovascular risk factors for Alzheimer's disease.",,"Nonaka, T.;Yakushiji, Y.;Ide, T.;Ito, H.;Kawamoto, K.;Hara, H.",2016,May 31,10.5692/clinicalneurol.cn-000860,0,
2217,Classification of delusions in Alzheimer's disease and their neural correlates,"BACKGROUND: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single-photon emission computed tomography data. METHODS: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty-five of the patients also had single-photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. RESULTS: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. CONCLUSIONS: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/*diagnosis/psychology;Brain/radionuclide imaging;Cerebrovascular Circulation;Delusions/classification/complications/*diagnosis/*psychology;Factor Analysis, Statistical;Female;Humans;Male;Middle Aged;Neuropsychological Tests/statistics & numerical data;Regional Blood Flow;Retrospective Studies;Tomography, Emission-Computed, Single-Photon/methods","Nomura, K.;Kazui, H.;Wada, T.;Sugiyama, H.;Yamamoto, D.;Yoshiyama, K.;Shimosegawa, E.;Hatazawa, J.;Takeda, M.",2012,Sep,10.1111/j.1479-8301.2012.00427.x,0,
2218,"Autosomal dominant childhood onset slowly progressive leukodystrophy - A Japanese family with spastic paraparesis, ataxia, mental deterioration, and skeletal abnormality","Autosomal dominant leukodystrophy is an extremely rare disease. Here we report on a dominantly inherited disease in a Japanese family with slowly progressive clinical course. Their symptoms and signs started in early childhood and very slowly progressed. In most patients spastic gait was the initial symptom. Neurological manifestations were characterized by pyramidal signs, ataxia, and mental deterioration. In addition to these neurological signs, the skeletal anomalies such as scoliosis and congenital hip dislocation were also present. MR images showed no abnormality in the early stage, but T2-weighted images revealed high intensity areas in the cerebral and cerebellar white matter, and the dentate nucleus in the advanced stage. Proton MR spectroscopy showed decrease of N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the advanced stage. Proton MR spectroscopy revealed normal N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the early stage. We suggested that these patients had abnormality in the white matter when MRI was still normal. We considered that intracranial demyelination was gradually progressed as the symptoms got aggravated. © 2004 Elsevier B.V. All rights reserved.",,"Nomoto, N.;Iwasaki, Y.;Arasaki, K.;Fujioka, T.;Kurihara, T.;Wakata, N.",2004,15,,0,
2219,Multiple solitary lesions in deep white matter in the early stage of Creutzfeldt-Jakob disease. A case report,"A 56-year-old housewife was admitted to our hospital because of involuntary movement on her left arm. Her neurological examination on admission showed mild weakness of her left arm and cerebeller ataxia. She developed periodic synchronous discharge on electroencephalogram and her cerebrospinal fluid revealed elevated level of neuron-specific enolase. Thereafter she developed dementia, followed by apallic state and diagnosed as having Creutzfeldt-Jakob disease (CJD). Interestingly, her MRI on admisson revealed multiple solitary lesions in deep cerebral white matter, which were detected as high signal intensity by T(2) weighed image. A few months later, these lesions tended to extend, and finally fused around the lateral ventricle in parallel with remarkable cortical atrophy. We excluded other diseases such as cerebrovasculer disorders. Finally, we concluded the white matter change seen from early stage in this case may be the lesion associated with CJD, and the CJD case with early white matter changes has been seldomly described.",,"Nomoto, K.;Murahashi, M.;Jimi, T.;Wakayama, Y.",1997,June,,0,
2220,White Matter Hyperintensities in Mild Cognitive Impairment and Lower Risk of Cognitive Decline,"BACKGROUND: White matter hyperintensities (WMH) may have a different impact on cognitive decline depending on strategic localization. OBJECTIVE: The goal of this study is to assess the impact of global and cholinergic WMH on cognitive decline of mild cognitive impairment (MCI) patients in the ADNI-1 dataset. METHODS: This is a retrospective analysis of data from a natural history study. MRI scans (T2 and PD sequences) were assessed with two visual scales: 1) The Cholinergic Pathways HyperIntensities Scale (CHIPS) score, designed to assess WMH in the cholinergic tracts, and 2) the Age-Related White Matter Changes Scale (ARWMC), a scale to assess the global WMH burden. All subjects underwent standardized neuropsychological testing. RESULTS: Subjects included 310 individuals with MCI. Analysis showed no association between WMH at baseline and conversion from MCI to Alzheimer's disease (AD), either for the global WMH burden or WMH within the cholinergic pathways. However, ARWMC scores had a significant confounding effect (p = 0.03) on conversion to dementia (hazard ratio of 0.37) among MCI subjects with low executive functions. CONCLUSION: We found no association between the burden of WMH at baseline in MCI and conversion to AD over 3 years. However, a higher global WMH burden appears to reduce the risk of conversion to AD in subjects with low executive functions. These results suggest that higher WMH burden in MCI individuals may be associated with a more gradual cognitive decline or stabilization, compared to a low WMH burden.",Adni;Alzheimer's disease;cholinergic pathways;executive functions;mild cognitive impairment;white matter hyperintensities,"Nolze-Charron, G.;Mouiha, A.;Duchesne, S.;Bocti, C.",2015,,10.3233/jad-140618,0,
2221,Clinically Silent Brain Infarcts,"The constant improvement of modern imaging techniques and their widespread use has led to the discovery of so-called clinically silent cerebral infarcts. Clinically silent brain infarcts (also labelled silent stroke) can be found in apparently healthy people, but especially in patients with arterial hypertension, evidence of atherosclerosis in the carotid arteries, cigarette smoking, atrial fibrillation, metabolic syndrome and in association with various laboratory parameters. The term silent often refers to the medical history and a standard neurological examination. It does not consider less obvious neuropsychological deficits. In contrast, neuropsychological deficits can be found in patients with putative clinically silent cerebral infarction frequently. The term uncovered cerebral infarction may therefore be more accurate. The detection of clinically uncovered brain infarcts is associated with an increased risk of clinically evident stroke and with the development of dementia. Patients with clinically silent cerebral infarction should therefore be screened for vascular risk factors and possible stroke etiology. Appropriate treatment measures should be implemented.",,"Nolte, C. H.",2014,19,,0,
2222,Cutaneous sensory and autonomic denervation in CADASIL,"Objective: To assess the involvement of the peripheral nervous system in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by means of immunofluorescence and confocal analysis of punch skin biopsies. Methods: We recruited 14 unrelated patients with CADASIL (M/F 9/5; age 53.9 ± 10.5 years) and 52 healthy controls (M/F 31/21; age 53.8 ± 9.8). Patients underwent clinical and neuroradiologic assessment. Three-millimeter punch skin biopsies were taken from the fingertip, the thigh, and the distal leg and processed using indirect immunofluorescence and a panel of primary antibodies to mark vessels and sensory and autonomic nerve fibers. Intraepidermal nerve fibers (IENF), Meissner corpuscles (MC), and sudomotor, vasomotor, and pilomotor nerves were assessed using confocal microscopy. Results: In patients, compared to controls, we found a severe loss of IENF at the distal leg (p < 0.01), at the thigh (p < 0.01), and at the fingertip (p < 0.01) with a non-length-dependent pattern and a loss of MC (p < 0.01). A severe sudomotor, vasomotor, and pilomotor nerve fiber loss was found by semiquantitative evaluation. Along with nerve loss, a severe derangement of the vascular bed was observed. In our patient population, sensory and autonomic denervation did not correlate with age, sex, type of mutation, or MRI involvement. Conclusions: We found an involvement of the peripheral nervous system in patients with CADASIL through the assessment of cutaneous somatic and autonomic nerves. The neurovascular derangement observed in the skin may reflect, although to a lesser extent, what happens in the CNS.",adult;age distribution;article;autonomic denervation;autonomic nerve;CADASIL;confocal microscopy;controlled study;female;gene mutation;human;immunofluorescence;major clinical study;male;mechanoreceptor;Meissner corpuscle;middle aged;nerve fiber;neuroradiology;nuclear magnetic resonance imaging;peripheral neuropathy;priority journal;punch biopsy;sex difference;skin biopsy;skin sensation;vasomotor reflex,"Nolano, M.;Provitera, V.;Donadio, V.;Caporaso, G.;Stancanelli, A.;Califano, F.;Pianese, L.;Liguori, R.;Santoro, L.;Ragno, M.",2016,,,0,
2223,The Role of Cerebrovascular Disease in Amyloid Deposition,"BACKGROUND: Some patients clinically diagnosed with subcortical vascular cognitive impairment (SVCI) have co-morbidity with AD pathology. OBJECTIVE: We investigated topographical differences in amyloid burden between SVCI and Alzheimer's disease type cognitive impairment (ADCI) using [11C] Pittsburgh compound B (PiB) positron emission tomography (PET). The purpose of this study was to investigate the role of cerebrovascular disease (CVD) in amyloid deposition. METHODS: We recruited 44 patients with SVCI and 44 patients with ADCI (amnestic mild cognitive impairment or Alzheimer's disease) with absent or minimal white matter hyperintensities, all with PiB-positive PET scans [PiB+]. As controls, we included 13 participants with normal cognition and PiB-negative scans. We divided the SVCI and ADCI patients into three groups according to global PiB retention ratio of SVCI, and then compared the tertiles in terms of the distribution of PiB retention using statistical parametric mapping analyses. Lobar to global PiB retention ratio and asymmetry indices were also compared between SVCI and ADCI groupsResults: Compared to PiB+ ADCI patients, PiB+ SVCI patients exhibited: 1) increased left-right asymmetry, and increased anterior-posterior difference; and 2) increased PiB retention in the parietal cortex, the occipital cortex and the precuneus-posterior cingulate cortex. In contrast, ADCI patients showed increased PiB retention in the striatum. When stratified by level of PiB retention, each group showed different characteristics. CONCLUSION: Our results showed that the distribution of amyloid deposition differed between patients with PiB+ SVCI and ADCI. These suggest that CVD contribute to and alter the known progression pattern in amyloid deposition in Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/psychology;Cerebrovascular Disorders/ diagnostic imaging/psychology;Cognitive Dysfunction/ diagnostic imaging/psychology;Dementia, Vascular/diagnostic imaging/psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging/methods;Male;Plaque, Amyloid/ diagnostic imaging/psychology;Positron-Emission Tomography/methods;Prospective Studies;Alzheimer's disease;cerebrovascular disease;magnetic resonance imaging;positron emission tomography;vascular dementia parallel","Noh, Y.;Seo, S. W.;Jeon, S.;Lee, J. M.;Kim, J. S.;Lee, J. H.;Kim, J. H.;Kim, G. H.;Ye, B. S.;Cho, H.;Kim, H. J.;Yoon, C. W.;Choe, Y. S.;Lee, K. H.;Weiner, M. W.;Na, D. L.",2016,Oct 4,,0,
2224,The Role of Cerebrovascular Disease in Amyloid Deposition,"BACKGROUND: Some patients clinically diagnosed with subcortical vascular cognitive impairment (SVCI) have co-morbidity with AD pathology. OBJECTIVE: We investigated topographical differences in amyloid burden between SVCI and Alzheimer's disease type cognitive impairment (ADCI) using [11C] Pittsburgh compound B (PiB) positron emission tomography (PET). The purpose of this study was to investigate the role of cerebrovascular disease (CVD) in the amyloid deposition. METHODS: We recruited 44 patients with SVCI and 44 patients with ADCI (amnestic mild cognitive impairment or Alzheimer's disease) with absent or minimal white matter hyperintensities, all with PiB-positive PET scans [PiB+]. As controls, we included 13 participants with normal cognition and PiB-negative scans. We divided the SVCI and ADCI patients into three groups according to global PiB retention ratio of SVCI, and then compared the tertiles in terms of the distribution of PiB retention using statistical parametric mapping analyses. Lobar to global PiB retention ratio and asymmetry indices were also compared between SVCI and ADCI groupsResults: Compared to PiB+ ADCI patients, PiB+ SVCI patients exhibited: 1) increased left-right asymmetry, and increased anterior-posterior difference; and 2) increased PiB retention in the parietal cortex, the occipital cortex and the precuneus-posterior cingulate cortex. In contrast, ADCI patients showed increased PiB retention in the striatum. When stratified by level of PiB retention, each group showed different characteristics. CONCLUSION: Our results showed that the distribution of amyloid deposition differed between patients with PiB+ SVCI and ADCI. These suggest that CVD contribute to and alter the known progression pattern in amyloid deposition in Alzheimer's disease.",Alzheimer's disease;cerebrovascular disease;magnetic resonance imaging;positron emission tomography;vascular dementia parallel,"Noh, Y.;Seo, S. W.;Jeon, S.;Lee, J. M.;Kim, J. S.;Lee, J. H.;Kim, J. H.;Kim, G. H.;Ye, B. S.;Cho, H.;Kim, H. J.;Yoon, C. W.;Choe, Y. S.;Lee, K. H.;Weiner, M. W.;Na, D. L.",2016,Aug 18,10.3233/jad-150832,0,2223
2225,White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers,"Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C-Pittsburgh compound B (PiB) PET. We recruited 53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (beta = 7.0 x 10-3, p = 0.034) while no significant correlation was found in APOE4 carriers (beta = -9.0 x 10-3, p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD.","Aged;Aged, 80 and over;Amyloid beta-Peptides/*metabolism;Aniline Compounds;Apolipoprotein E4/genetics;Brain/pathology/radionuclide imaging;Cognition Disorders/*complications/pathology/radionuclide imaging;Dementia, Vascular/*complications/pathology/radionuclide imaging;Female;Humans;Leukoencephalopathies/*etiology/pathology/radionuclide imaging;Male;Neuropsychological Tests;Positron-Emission Tomography;Regression Analysis;Retrospective Studies;Statistics as Topic;Thiazoles;Alzheimer's disease;amyloid burden;apolipoprotein E4;cerebrovascular disease","Noh, Y.;Seo, S. W.;Jeon, S.;Lee, J. M.;Kim, J. H.;Kim, G. H.;Cho, H.;Yoon, C. W.;Kim, H. J.;Ye, B. S.;Kim, S. T.;Choe, Y. S.;Lee, K. H.;Kim, J. S.;Ewers, M.;Weiner, M. W.;Lee, J. H.;Werring, D. J.;Kang, D. R.;Kim, C. S.;Na, D. L.",2014,,10.3233/jad-130461,0,
2226,A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities,"The Clinical Research Center for Dementia of South Korea (CREDOS) group developed a new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities (WMHs). In this study, we aimed to evaluate the validity of the CREDOS ischemia classification system. A total of 352 patients with cognitive impairments were included. Their WMH scores were rated using the CREDOS WMH visual rating scale. These patients were divided into 3 groups according to the CREDOS ischemia classification system. The volume of WMH was also automatically measured. The number of lacunes and microbleeds (MBs) were counted. The CREDOS ischemia classification system was revised with factor analysis using vascular risk factors and cerebrovascular disease (CVD) markers (WMH volume, lacunes, and MBs). External validation was performed in another group of patients with cognitive impairment using multinomial logistic regression analysis. The CREDOS WMH visual rating scale showed excellent correlation with the automatically measured volume of WMH. The factor analysis showed that the severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia classification system. In the validation group, the presence of vascular risk factors and the severity of CVD markers could be distinguished according to the revised CREDOS ischemia classification. We validated a newly developed classification system for ischemia. This simple visual classification system was capable of providing information on vascular risk factors and CVD markers by simply rating WMH on magnetic resonance imaging.","Aged;Aged, 80 and over;Brain/ pathology;Brain Ischemia/ classification/pathology;Cerebral Ventricles/ pathology;Cohort Studies;Dementia/classification/pathology;Female;Humans;Infarction, Middle Cerebral Artery/classification/pathology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Reproducibility of Results;Risk Factors","Noh, Y.;Lee, Y.;Seo, S. W.;Jeong, J. H.;Choi, S. H.;Back, J. H.;Woo, S. Y.;Kim, G. H.;Shin, J. S.;Kim, C. H.;Cho, H.;Park, J. S.;Lee, J. M.;Hong, C. H.;Kim, S. Y.;Lee, J. H.;Park, K. H.;Han, S. H.;Cheong, H. K.;Na, D. L.",2014,Apr,10.1016/j.jstrokecerebrovasdis.2013.06.002,0,
2227,Emotional disturbance in CADASIL: its impact on quality of life and caregiver burden,"BACKGROUND AND PURPOSE: Recurrent strokes and cognitive dysfunction are the major symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, emotional disturbances in CADASIL patients are incompletely understood. The aim of this study was to investigate emotional disturbances in CADASIL and their impact on the patients' quality of life (QOL) and caregiver burden. METHODS: From 54 patients who were diagnosed as CADASIL between January 2000 and August 2012 in the Asan Medical Center, Seoul, Korea, 23 patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale was used for the assessment of depressive emotional disturbances (DED). For nondepressive emotional disturbances (NDED), the criteria of Kim and Choi-Kwon [Neurology 2000;54:1805-1810] were used for emotional incontinence (excessive/inappropriate expression of laughing or crying), and the modified Spielberger Trait Anger Scale was used for anger proneness (excessive/inappropriate expression of anger). Patients' QOL and caregiver burden were assessed with stroke-specific emotional QOL and the Sense of Competence Questionnaire (SCQ), respectively. Functional disability was assessed by the modified Rankin scale (mRS), and white matter ischemic changes and microbleeds were analyzed using brain magnetic resonance images. RESULTS: Twelve patients (52.2%) had various emotional disturbances including DED (n=10, 43.5%) and NDED (n=7, 30.4%). The presence of any emotional disturbances was associated with thalamic (p=0.012) and cortical (p=0.037) microbleeds, mRS (p=0.001), cognitive impairment (p=0.002), patients' low QOL (p=0.009) and increased caregiver burden (p=0.002). DED was associated with multiple (>/=10) microbleeds (p=0.039), cognitive impairment (p=0.030) and mRS (p=0.030), and negatively influenced all domains of patients' QOL and caregiver burden. NDED was associated with cortical microbleeds (p=0.017) and mRS (p=0.014). Unlike DED, NDED was not associated with patients' poor QOL, except for thinking domain, but was significantly related to total SCQ and subscales 1 and 2 of SCQ (p=0.012). CONCLUSIONS: More than half the CADASIL patients had emotional disturbances, either DED or NDED. Both are associated with patients' poor QOL and increased caregiver burden, the former more markedly than the latter. Considering that CADASIL is a progressive disease with deteriorating patients' QOL, physicians have to pay more attention to emotional problems in CADASIL patients. Treatment strategies should be investigated in this regard to improve patients' QOL and reduce caregiver burden.",Activities of Daily Living;Affective Symptoms/ etiology/psychology;Aged;Basal Ganglia/pathology;Brain/pathology;Brain Stem/pathology;CADASIL/pathology/ psychology;Caregivers/ psychology;Cerebral Cortex/pathology;Cerebral Hemorrhage/etiology/pathology/psychology;Cognition Disorders/etiology/pathology;Depression/etiology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Quality of Life;Risk Factors;Severity of Illness Index;Thalamus/pathology,"Noh, S. M.;Chung, S. J.;Kim, K. K.;Kang, D. W.;Lim, Y. M.;Kwon, S. U.;Kim, J. S.",2014,,10.1159/000357798,0,
2228,Blood viscosity in subcortical vascular mild cognitive impairment with versus without cerebral amyloid burden,"BACKGROUND: Subcortical vascular dementia (SVaD) is a common form of dementia, attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid deposition may not show differences in BV because their small-vessel disease may result from amyloid angiopathy independently of BV. We, therefore, hypothesized that BV might show different changes compared with control subjects in subcortical vascular mild cognitive impairment (svMCI) that refers to the prodromal stage of SVaD according to cerebral amyloid burden detected by the [(11)C] Pittsburgh compound B (PiB) PET (positron emission tomography), and apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and parenchymal amyloid). METHODS: Our subjects consisted of 33 healthy normal controls (NC), 28 patients with PiB(-) svMCI, and 12 with PiB(+) svMCI. They underwent scanning capillary tube viscometer measuring BV during systolic and diastolic phases. RESULTS: Compared with the NC group, the PiB(-) svMCI group showed increased diastolic blood viscosity (DBV) but no difference in systolic blood viscosity (SBV). By contrast, there was no significant difference in SBV and DBV between the NC and PiB(+) svMCI groups. Within the PiB(+) svMCI group, ApoE4(-) subgroup showed increased DBV compared with the ApoE4(+) subgroup. CONCLUSIONS: Increased DBV is an important contributor to the development of ""pure"" svMCI (ie, without cerebral amyloid deposition). The relationship between BV and PiB(+) svMCI differed according to ApoE genotype, suggesting that the pathogenesis of PiB(+) svMCI might also be heterogeneous.","Aged;Aged, 80 and over;Aniline Compounds;Apolipoprotein E4/genetics;*Blood Viscosity;Case-Control Studies;Cerebral Amyloid Angiopathy/*blood/diagnosis/genetics;Dementia, Vascular/*blood/diagnosis/genetics;Female;Genetic Predisposition to Disease;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/*blood/diagnosis/genetics;Neuropsychological Tests;Phenotype;Positron-Emission Tomography;Predictive Value of Tests;Prospective Studies;Radiopharmaceuticals;Risk Factors;Thiazoles;Hemodynamic;Mri;amyloid;artherosclerosis;vascular dementia","Noh, H. J.;Seo, S. W.;Jeong, Y.;Park, J. E.;Kim, G. H.;Noh, Y.;Cho, H.;Kim, H. J.;Yoon, C. W.;Ye, B. S.;Werring, D. J.;Na, D. L.",2014,May-Jun,10.1016/j.jstrokecerebrovasdis.2013.08.004,0,
2229,Cerebral Amyloid Angiopathy-Related Microbleeds and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease,"BACKGROUND: Alzheimer's disease (AD) commonly accompanies cerebral amyloid angiopathy (CAA). OBJECTIVE: We aimed to reveal associations between CAA-related brain microbleeds and cerebrospinal fluid (CSF) markers in AD patients. METHODS: Patients with probable AD (n = 88) from consecutive patients in our memory clinic were evaluated for patient demographics, vascular risk factors, neuropsychological tests, apolipoprotein E phenotype, MRI including T2*-weighted image and fluid attenuated inversion recovery sequence, and CSF amyloid and tau markers. RESULTS: The 88 patients with AD included 15 with microbleeds only in cortical/subcortical regions (cortical microbleeds) that could be CAA-related, 16 with microbleeds only in deep locations (deep microbleeds), 3 with microbleeds in both cortical and deep locations (mixed microbleeds), and 54 without microbleeds. The CSF levels of amyloid beta-protein 1-40 (Abeta40) and amyloid beta-protein 1-42 (Abeta42) were significantly lower in patients with cortical microbleeds than in those without microbleeds (p = 0.001 and p = 0.027, respectively). The result remained unchanged after adjustment for age, sex, apolipoprotein E E4 presence, and leukoaraiosis. CONCLUSIONS: CAA-related cortical microbleeds would be associated with lower CSF levels of Abeta40 and Abeta42 in AD, reflecting the deposition of both Abeta40 and Abeta42 in the cerebrovasculature.",Alzheimer's disease;biomarkers;cerebral amyloid angiopathy;cerebrospinal fluid,"Noguchi-Shinohara, M.;Komatsu, J.;Samuraki, M.;Matsunari, I.;Ikeda, T.;Sakai, K.;Hamaguchi, T.;Ono, K.;Nakamura, H.;Yamada, M.",2017,,,0,
2230,Juvenile form of Alexander disease with GFAP mutation and mitochondrial abnormality,"The authors report a 29-year-old woman with marked atrophy of the cerebellum, medulla oblongata, and spinal cord, dementia, diffuse white matter abnormality on MRI, ragged-red fibers, and R88C mutation in the human glial fibrillary acidic protein (GFAP). Mitochondria DNA (mtDNA) analysis showed a rare polymorphism at A8291G. This mtDNA polymorphism, which has been associated with limb-girdle type mitochondrial myopathy, may modify the clinical symptoms of this juvenile form of Alexander disease with GFAP mutation.",glial fibrillary acidic protein;mitochondrial DNA;adult;Alexander disease;anamnesis;article;brain atrophy;brain mitochondrion;case report;cerebellum atrophy;clinical feature;controlled study;dementia;disease association;DNA determination;DNA polymorphism;DNA sequence;female;gene deletion;gene identification;gene mutation;human;human tissue;limb girdle muscular dystrophy;medulla oblongata;muscle biopsy;neurologic examination;nuclear magnetic resonance imaging;priority journal;sequence analysis;spinal cord atrophy;symptom;white matter,"Nobuhara, Y.;Nakahara, K.;Higuchi, I.;Yoshida, T.;Fushiki, S.;Osame, M.;Arimura, K.;Nakagawa, M.",2004,,,0,
2231,Brain SPECT in subtypes of mild cognitive impairment. Findings from the DESCRIPA multicenter study,"The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer's Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer's disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.","Aged;Alzheimer Disease/physiopathology/*radionuclide imaging;Amnesia/diagnosis/physiopathology/radionuclide imaging;Analysis of Variance;Attention/physiology;Brain/physiopathology/*radionuclide imaging;Cerebral Cortex/physiopathology/radionuclide imaging;Cerebrovascular Circulation/physiology;Cognition/physiology;Cognition Disorders/physiopathology/*radionuclide imaging;Female;Frontal Lobe/physiopathology/radionuclide imaging;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests/statistics & numerical data;Severity of Illness Index;Technetium Tc 99m Exametazime;Temporal Lobe/physiopathology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon/*methods;Verbal Learning/physiology","Nobili, F.;Frisoni, G. B.;Portet, F.;Verhey, F.;Rodriguez, G.;Caroli, A.;Touchon, J.;Calvini, P.;Morbelli, S.;De Carli, F.;Guerra, U. P.;Van de Pol, L. A.;Visser, P. J.",2008,Sep,10.1007/s00415-008-0897-4,0,
2232,Impaired quantitative cerebral blood flow in scleroderma patients,"Systemic Sclerosis (SSc) is a multisystem disease characterised by proliferation of vascular tissue, obliterative microvascular lesions and diffuse organ fibrosis. Despite widespread vascular disease, Central Nervous System complaints are only infrequently reported and it is uncertain whether they merely derive from systemic complications or whether they may be also caused by a primary vascular process within the brain. Regional cerebral blood flow (rCBF) was quantitatively measured by the 133Xenon clearance technique in twenty-seven consecutive SSc patients without relevant systemic complications and with different severity of vascular involvement, as staged by nailfold capillary videomicroscopy (NCV). Absolute, percent, and asymmetry rCBF values were compared (z-statistics) with age- and sex-matched healthy controls. Cerebral MRI and Mini-Mental State Examination (MMSE) were also performed. Doppler sonography of neck vessels and Transcranial Doppler sonography (TCD) were performed in patients presenting rCBF reduction. Cerebral hypoperfusion was found in the 52% of patients, i.e.: in 33% of patients with the 'early' NCV pattern, in 56% of patients with the 'active' pattern, and in 67% of patients with the 'late' NCV pattern. Thirty percent were the MRIs showing focal and/or diffuse signal abnormalities in the white matter of both hemispheres with the highest rate (44%) in the 'late' NCV pattern. MMSE disclosed mild dementia in one patient in the 'late' NCV group and some mistakes in 6 more patients, in the 'active' or 'late' NCV groups, whereas TCD failed to find significant stenosis of Willis' arteries. Cerebral hypoperfusion is shown for the first time in a substantial part of SSc patients without either neurological symptoms or relevant systemic complications. It is suggested that the rCBF reduction might be related to the systemic scleroderma microangiopathy although, probably due to the paucity of connective tissue in cerebral vessels, the vast majority of patients remains in a subclinical phase.","Adult;Aged;Angiography;*Cerebrovascular Circulation;Female;Humans;Magnetic Resonance Imaging;Male;Microcirculation;Middle Aged;Scleroderma, Systemic/*physiopathology/ultrasonography;Ultrasonography, Doppler, Transcranial;Xenon Radioisotopes","Nobili, F.;Cutolo, M.;Sulli, A.;Castaldi, A.;Sardanelli, F.;Accardo, S.;Rosadini, G.;Rodriguez, G.",1997,Nov 6,,0,
2233,Comparative Analysis of Cortical Microinfarcts and Microbleeds using 3.0-Tesla Postmortem Magnetic Resonance Images and Histopathology,"Microvascular lesions including cortical microinfarctions (CMIs) and cerebral lobar microbleeds (CMBs) are usually caused by cerebral amyloid angiopathy (CAA) in the elderly and are correlated with cognitive decline. However, their radiological-histopathological coincidence has not been revealed systematically with widely used 3-Tesla (3T) magnetic resonance imaging (MRI). The purpose of the present study is to delineate the histopathological background corresponding to MR images of these lesions. We examined formalin-fixed 10-mm thick coronal brain blocks from 10 CAA patients (five were also diagnosed with Alzheimer's disease, three with dementia with Lewy bodies, and two with CAA only) with dementia and six non CAA patients with neurodegenerative disease. Using 3T MRI, both 3D-fluid attenuated inversion recovery (FLAIR) and 3D-double inversion recovery (DIR) were examined to identify CMIs, and T2* and susceptibility-weighted images (SWI) were examined to identify CMBs. These blocks were subsequently examined histologically and immunohistochemically. In CAA patients, 48 CMIs and 6 lobar CMBs were invariably observed in close proximity to degenerated Abeta-positive blood vessels. Moreover, 16 CMIs (33%) of 48 were detected with postmortem MRI, but none were seen when the lesion size was smaller than 1 mm. In contrast, only 1 undeniable CMI was founded with MRI and histopathology in 6 non CAA patients. Small, cortical high-intensity lesions seen on 3D-FLAIR and 3D-DIR images likely represent CMIs, and low-intensity lesions in T2* and SWI correspond to CMBs with in vivo MRI. Furthermore, a close association between amyloid-laden vessels and these microvascular lesions indicated the contribution of CAA to their pathogenesis.",Autopsy;bleeding;cerebral amyloid angiopathy;dementia;infarct;magnetic resonance imaging;pathology,"Niwa, A.;Ii, Y.;Shindo, A.;Matsuo, K.;Ishikawa, H.;Taniguchi, A.;Takase, S.;Maeda, M.;Sakuma, H.;Akatsu, H.;Hashizume, Y.;Tomimoto, H.",2017,,,0,
2234,The relation between the change of the brain imaging and cognitive level about Alzheimer disease and Binswanger disease,"Aim. To clarify the recognize level and imaging between Alzheimer disease (AD) and Binswanger disease, and to discover the clinical distinguish. Methods. The CT materials of 42 cases Binswanger patients and 23 cases AD petients and 11 items scores were analysis. Results. It showed lower scores in the tempral and site orientation language and recent memory, attention and calculation and drawing in AD and Binswanger. The CT imaging characteristic of Binswanger was low density area in periventricular white matter and multipal locular cerebral infarction white the CT imaging characteristic of AD group was the grey matter shrivel and the lateral ventricle bigger. Conclusion. The main methods to distinguish AD and Binswanger is through CT examination. The congnitive impairment is more serious and extensive in AD than in Binswanger.",,"Niu, J.",2003,Apr,,0,
2235,Brain atrophy and cerebral small vessel disease: a prospective follow-up study,"BACKGROUND AND PURPOSE: cerebral small vessel disease (SVD) is the most common cause of vascular dementia. Interest in the use of surrogate markers is increasing. The aims of this study were to determine if brain volume was different between patients with SVD and control subjects, whether it correlated with cognition in SVD, and whether changes in brain volume could be detected during prospective follow-up. METHODS: thirty-five patients (mean age, 68.8 years) who had a lacunar stroke and radiological evidence of confluent leukoaraiosis and 70 age- and gender-matched control subjects were recruited. Whole-brain T1-weighted imaging and neuropsychological testing were performed after 1 year on all patients and after 2 years for the control subjects. Fully automated software was used to determine brain volume and percentage brain volume change. An executive function score was derived. RESULTS: there was a significant difference in brain volume between the patients with SVD and control subjects (mean +/- SD [mL] 1529 +/- 84 versus 1573 +/- 69, P=0.019). In the patients with SVD, there was a significant association between brain volume and executive function (r=0.501, P<0.05). The mean +/- SD yearly brain atrophy rate for patients with SVD and control subjects was significantly different (-0.914% +/- 0.8% versus -0.498% +/- 0.4%, respectively, P=0.017). No change in executive function score was detected over this period. CONCLUSIONS: brain volume is reduced in SVD and a decline is detectable prospectively. The correlation with executive function at a cross-sectional level and the change in brain volume with time are both promising for the use of brain atrophy as a surrogate marker of SVD progression.","Aged;Atrophy;Biomarkers;Brain/ pathology;Dementia, Vascular/etiology/pathology;Female;Follow-Up Studies;Humans;Leukoaraiosis/etiology/ pathology;Male;Middle Aged;Organ Size;Stroke/complications/ pathology","Nitkunan, A.;Lanfranconi, S.;Charlton, R. A.;Barrick, T. R.;Markus, H. S.",2011,Jan,10.1161/strokeaha.110.594267,0,
2236,Reduced N-acetylaspartate is consistent with axonal dysfunction in cerebral small vessel disease,"Background: Cerebral small vessel disease (SVD) is an important cause of cognitive impairment, but the pathophysiological mechanisms remain unclear. We used (1)H MRS to investigate brain metabolic differences between patients with SVD and controls and correlated this with cognition. Methods: 35 patients with SVD (lacunar stroke and radiological evidence of confluent leukoaraiosis) and 35 controls underwent multi-voxel spectroscopic imaging of white matter to obtain absolute metabolite concentrations of N-acetylaspartate (NAA), total creatines, total cholines, myo-inositol, and lactate. A range of cognitive tests was performed on patients with SVD, and composite scores were calculated. Results: Scans of sufficient quality for data analysis were available in 29 cases and 35 controls. NAA was significantly reduced in patients compared with controls (lower by 7.27%, P=0.004). However, when lesion load within each individual voxel (mean 22% in SVD vs 5% in controls, P<0.001) was added as a covariate, these differences were no longer significant, suggesting that the metabolite differences arose primarily from differences in lesioned tissue. In patients with SVD, there was no correlation between cognitive scores and any brain metabolite. No lactate, an indicator of anaerobic metabolism, was detected. Conclusions: The most consistent change in SVD is a reduction in NAA, a marker of neuronal integrity. The lack of correlation with cognition does not support the use of MRS as a surrogate disease marker. Copyright © 2008 John Wiley & Sons, Ltd.",,"Nitkunan, A.;Charlton, R. A.;Barrick, T. R.;McIntyre, D. J. O.;Howe, F. A.;Markus, H. S.",2009,2009,,0,
2237,Multimodal MRI in cerebral small vessel disease: Its relationship with cognition and sensitivity to change over time,"BACKGROUND AND PURPOSE-Cerebral small vessel disease is the most common cause of vascular dementia. Interest in using MRI parameters as surrogate markers of disease to assess therapies is increasing. In patients with symptomatic sporadic small vessel disease, we determined which MRI parameters best correlated with cognitive function on cross-sectional analysis and which changed over a period of 1 year. METHODS-Thirty-five patients with lacunar stroke and leukoaraiosis were recruited. They underwent multimodal MRI (brain volume, fluid-attenuated inversion recovery lesion load, lacunar infarct number, fractional anisotropy, and mean diffusivity from diffusion tensor imaging) and neuropsychological testing. Twenty-seven agreed to reattend for repeat MRI and neuropsychology at 1 year. RESULTS-An executive function score correlated most strongly with diffusion tensor imaging (fractional anisotropy histogram, r≤'0.640, P≤0.004) and brain volume (r≤0.501, P≤0.034). Associations with diffusion tensor imaging were stronger than with all other MRI parameters. On multiple regression of all imaging parameters, a model that contained brain volume and fractional anisotropy, together with age, gender, and premorbid IQ, explained 74% of the variance of the executive function score (P≤0.0001). Changes in mean diffusivity and fractional anisotropy were detectable over the 1-year follow-up; in contrast, no change in other MRI parameters was detectable over this time period. CONCLUSION-A multimodal MRI model explains a large proportion of the variation in executive function in cerebral small vessel disease. In particular, diffusion tensor imaging correlates best with executive function and is the most sensitive to change. This supports the use of MRI, in particular diffusion tensor imaging, as a surrogate marker in treatment trials. © 2008 American Heart Association, Inc.",,"Nitkunan, A.;Barrick, T. R.;Charlton, R. A.;Clark, C. A.;Markus, H. S.",2008,1,,0,
2238,Diagnosis by whole exome sequencing of atypical infantile onset Alexander disease masquerading as a mitochondrial disorder,"Introduction There are many similarities, both clinical and radiological, between mitochondrial leukoencephalopathies and Alexander disease, an astrogliopathy. Clinically, both can manifest with a myriad of symptoms and signs, arising from the neonatal period to adulthood. Radiologically, both can demonstrate white matter changes, signal abnormalities of basal ganglia or thalami, brainstem abnormalities and contrast enhancement of white matter structures. Magnetic resonance spectroscopy may reveal elevation of lactate in the abnormal white matter in Alexander disease making the distinction even more challenging. Patient and Methods We present a child who was considered to have an infantile onset mitochondrial disorder due to a combination of neurological symptoms and signs (developmental regression, failure to thrive, episodic deterioration, abnormal eye movements, pyramidal and cerebellar signs), urinary excretion of 3-methyl-glutaconic acid and imaging findings (extensive white matter changes and cerebellar atrophy) with a normal head circumference. Whole exome sequence analysis was performed. Results The child was found to harbor the R416W mutation, one of the most prevalent mutations in the glial fibrillary acidic protein (GFAP) gene that causes Alexander disease. Conclusions Alexander disease should be considered in the differential diagnosis of infantile leukoencephalopathy, even when no macrocephaly is present. Next generation sequencing is a useful aid in unraveling the molecular etiology of leukoencephalopathies. © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.",,"Nishri, D.;Edvardson, S.;Lev, D.;Leshinsky-Silver, E.;Ben-Sira, L.;Henneke, M.;Lerman-Sagie, T.;Blumkin, L.",2014,July,,0,
2239,Diffusion tensor imaging reveals visual pathway damage in patients with mild cognitive impairment and Alzheimer's disease,"Visual deficits are commonly seen in patients with Alzheimer's disease (AD), but postmortem histology has not found substantial damage in visual cortex regions, leading to the hypothesis that the visual pathway, from eye to the brain, may be damaged in AD. Diffusion tensor imaging (DTI) has been used to characterize white matter abnormalities. However, there is a lack of data examining the optic nerves and tracts in patients with AD. In this study, we used DTI to analyze the visual pathway in healthy controls, patients with mild cognitive impairment (MCI) and AD using scans provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found significant increases in the total diffusivity and radial diffusivity and reductions in fractional anisotropy in optic nerves among AD patients. Similar but less extensive changes in these metrics were seen in MCI patients as compared to controls. The differences in DTI metrics between groups mirrored changes in the splenium of the corpus callosum, which has commonly been shown to exhibit white matter damage during AD and MCI. Our findings indicate that white matter damage extends to the visual system, and may help explain the visual deficits experienced by AD patients.","Aged;Alzheimer Disease/ pathology;Corpus Callosum/pathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Mild Cognitive Impairment/ pathology;Optic Nerve/pathology;Retina/pathology;Statistics, Nonparametric;Visual Pathways/ pathology","Nishioka, C.;Poh, C.;Sun, S. W.",2015,,10.3233/jad-141239,0,
2240,Association of lipocalin-type prostaglandin D synthase with disproportionately enlarged subarachnoid-space in idiopathic normal pressure hydrocephalus,"Background: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable cause of dementia, gait disturbance, and urinary incontinence in elderly patients with ventriculomegaly. Its unique morphological feature, called disproportionately enlarged subarachnoid-space hydrocephalus (DESH), may also be a diagnostic feature. Lipocalin-type prostaglandin D synthase (L-PGDS) is a major cerebrospinal fluid (CSF) protein produced by arachnoid cells, and its concentration in the CSF is reportedly decreased in iNPH. L-PGDS acts as a prostaglandin D2-producing enzyme and behaves as a chaperone to prevent the neurotoxic aggregation of amyloid beta (Aβ) implicated in Alzheimer's disease, a major comorbidity of iNPH. The aim of this study was to confirm the L-PGDS decrease in DESH-type iNPH and to clarify its relationship with clinico-radiological features or other CSF biomarkers.Methods: We evaluated 22 patients (age: 76.4 ± 4.4 y; males: 10, females: 12) referred for ventriculomegaly without CSF pathway obstruction, and conducted a CSF tap test to determine the surgical indication. CSF concentrations of L-PGDS, Aβ42, Aβ40, and total tau (t-tau) protein were determined using enzyme-linked immunosorbent assays. Clinical symptoms were evaluated by the iNPH grading scale, mini-mental state examination, frontal assessment battery (FAB), and timed up and go test. The extent of DESH was approximated by the callosal angle, and the severity of parenchymal damage was evaluated by the age-related white matter change (ARWMC) score.Results: L-PGDS and t-tau levels in CSF were significantly decreased in DESH patients compared to non-DESH patients (p = 0.013 and p = 0.003, respectively). L-PGDS and t-tau showed a significant positive correlation (Spearman r = 0.753, p < 0.001). Among the clinico-radiological profiles, L-PGDS levels correlated positively with age (Spearman r = 0.602, p = 0.004), callosal angle (Spearman r = 0.592, p = 0.004), and ARWMC scores (Spearman r = 0.652, p = 0.001), but were negatively correlated with FAB scores (Spearman r = 0.641, p = 0.004).Conclusions: Our data support the diagnostic value of L-PGDS as a CSF biomarker for iNPH and suggest a possible interaction between L-PGDS and tau protein. In addition, L-PGDS might work as a surrogate marker for DESH features, white matter damage, and frontal lobe dysfunction. © 2014 Nishida et al.; licensee BioMed Central Ltd.",amyloid beta protein[1-40];amyloid beta protein[1-42];cholinesterase inhibitor;lipocalin;prostaglandin D synthase;tau protein;age related white matter change;aged;article;brain ventricle dilatation;cerebrospinal fluid analysis;clinical article;controlled study;dementia;disproportionately enlarged subarachnoid space hydrocephalus;enzyme linked immunosorbent assay;female;frontal assessment battery;human;male;meninx disorder;Mini Mental State Examination;assessment of humans;neuroimaging;normotensive hydrocephalus;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;prescription;priority journal;protein cerebrospinal fluid level;protein determination;subarachnoid space;Achieva Quasar,"Nishida, N.;Nagata, N.;Toda, H.;Jingami, N.;Uemura, K.;Ozaki, A.;Mase, M.;Urade, Y.;Matsumoto, S.;Iwasaki, K.;Ishikawa, M.",2014,,,0,
2241,Diffusion weighted imaging-based maximum density path analysis and classification of Alzheimer's disease,"Characterizing brain changes in Alzheimer's disease (AD) is important for patient prognosis and for assessing brain deterioration in clinical trials. In this diffusion weighted imaging study, we used a new fiber-tract modeling method to investigate white matter integrity in 50 elderly controls (CTL), 113 people with mild cognitive impairment, and 37 AD patients. After clustering tractography using a region-of-interest atlas, we used a shortest path graph search through each bundle's fiber density map to derive maximum density paths (MDPs), which we registered across subjects. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) along all MDPs and found significant MD and FA differences between AD patients and CTL subjects, as well as MD differences between CTL and late mild cognitive impairment subjects. MD and FA were also associated with widely used clinical scores. As an MDP is a compact low-dimensional representation of white matter organization, we tested the utility of diffusion tensor imaging measures along these MDPs as features for support vector machine based classification of AD.",aged;Alzheimer disease;article;cognitive defect;controlled study;diffusion tensor imaging;diffusion weighted imaging;disease classification;female;fractional anisotropy;human;image analysis;major clinical study;male;path analysis;prognosis;scoring system;support vector machine;tractography;white matter,"Nir, T. M.;Villalon-Reina, J. E.;Prasad, G.;Jahanshad, N.;Joshi, S. H.;Toga, A. W.;Bernstein, M. A.;Jack, C. R.;Weiner, M. W.;Thompson, P. M.",2015,,10.1016/j.neurobiolaging.2014.05.037,0,
2242,Diffusion weighted imaging-based maximum density path analysis and classification of Alzheimer's disease,"Characterizing brain changes in Alzheimer's disease (AD) is important for patient prognosis and for assessing brain deterioration in clinical trials. In this diffusion weighted imaging study, we used a new fiber-tract modeling method to investigate white matter integrity in 50 elderly controls (CTL), 113 people with mild cognitive impairment, and 37 AD patients. After clustering tractography using a region-of-interest atlas, we used a shortest path graph search through each bundle's fiber density map to derive maximum density paths (MDPs), which we registered across subjects. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) along all MDPs and found significant MD and FA differences between AD patients and CTL subjects, as well as MD differences between CTL and late mild cognitive impairment subjects. MD and FA were also associated with widely used clinical scores. As an MDP is a compact low-dimensional representation of white matter organization, we tested the utility of diffusion tensor imaging measures along these MDPs as features for support vector machine based classification of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ classification/diagnosis/ pathology;Anisotropy;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted/ methods;Male;Mild Cognitive Impairment/diagnosis/pathology;Neuroimaging/ methods;White Matter/pathology","Nir, T. M.;Villalon-Reina, J. E.;Prasad, G.;Jahanshad, N.;Joshi, S. H.;Toga, A. W.;Bernstein, M. A.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.",2015,Jan,10.1016/j.neurobiolaging.2014.05.037,0,
2243,"Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging","The Alzheimer's Disease Neuroimaging Initiative (ADNI) recently added diffusion tensor imaging (DTI), among several other new imaging modalities, in an effort to identify sensitive biomarkers of Alzheimer's disease (AD). While anatomical MRI is the main structural neuroimaging method used in most AD studies and clinical trials, DTI is sensitive to microscopic white matter (WM) changes not detectable with standard MRI, offering additional markers of neurodegeneration. Prior DTI studies of AD report lower fractional anisotropy (FA), and increased mean, axial, and radial diffusivity (MD, AxD, RD) throughout WM. Here we assessed which DTI measures may best identify differences among AD, mild cognitive impairment (MCI), and cognitively healthy elderly control (NC) groups, in region of interest (ROI) and voxel-based analyses of 155 ADNI participants (mean age: 73.5 +/- 7.4; 90 M/65 F; 44 NC, 88 MCI, 23 AD). Both VBA and ROI analyses revealed widespread group differences in FA and all diffusivity measures. DTI maps were strongly correlated with widely-used clinical ratings (MMSE, CDR-sob, and ADAS-cog). When effect sizes were ranked, FA analyses were least sensitive for picking up group differences. Diffusivity measures could detect more subtle MCI differences, where FA could not. ROIs showing strongest group differentiation (lowest p-values) included tracts that pass through the temporal lobe, and posterior brain regions. The left hippocampal component of the cingulum showed consistently high effect sizes for distinguishing groups, across all diffusivity and anisotropy measures, and in correlations with cognitive scores.",,"Nir, T. M.;Jahanshad, N.;Villalon-Reina, J. E.;Toga, A. W.;Jack, C. R.;Weiner, M. W.;Thompson, P. M.",2013,,10.1016/j.nicl.2013.07.006,0,
2244,Fractional anisotropy derived from the diffusion tensor distribution function boosts power to detect Alzheimer's disease deficits,"PURPOSE: In diffusion MRI (dMRI), fractional anisotropy derived from the single-tensor model (FA(DTI) ) is the most widely used metric to characterize white matter (WM) microarchitecture, despite known limitations in regions with crossing fibers. Due to time constraints when scanning patients in clinical settings, high angular resolution diffusion imaging acquisition protocols, often used to overcome these limitations, are still rare in clinical population studies. However, the tensor distribution function (TDF) may be used to model multiple underlying fibers by representing the diffusion profile as a probabilistic mixture of tensors. METHODS: We compared the ability of standard FA(DTI) and TDF-derived FA (FA(TDF) ), calculated from a range of dMRI angular resolutions (41, 30, 15, and 7 gradient directions), to profile WM deficits in 251 individuals from the Alzheimer's Disease Neuroimaging Initiative and to detect associations with 1) Alzheimer's disease diagnosis, 2) Clinical Dementia Rating scores, and 3) average hippocampal volume. RESULTS: Across angular resolutions and statistical tests, FA(TDF) showed larger effect sizes than FA(DTI) , particularly in regions preferentially affected by Alzheimer's disease, and was less susceptible to crossing fiber anomalies. CONCLUSION: The TDF ""corrected"" form of FA may be a more sensitive and accurate alternative to the commonly used FA(DTI) , even in clinical quality dMRI data. Magn Reson Med 78:2322-2333, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.",Alzheimer's disease;diffusion-weighted imaging;fractional anisotropy;tensor distribution function;white matter,"Nir, T. M.;Jahanshad, N.;Villalon-Reina, J. E.;Isaev, D.;Zavaliangos-Petropulu, A.;Zhan, L.;Leow, A. D.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.;Alzheimer's Diseaase Neuroimaginng, Initiative",2017,Dec,,0,2245
2245,Fractional anisotropy derived from the diffusion tensor distribution function boosts power to detect Alzheimer's disease deficits,"PURPOSE: In diffusion MRI (dMRI), fractional anisotropy derived from the single-tensor model (FADTI ) is the most widely used metric to characterize white matter (WM) microarchitecture, despite known limitations in regions with crossing fibers. Due to time constraints when scanning patients in clinical settings, high angular resolution diffusion imaging acquisition protocols, often used to overcome these limitations, are still rare in clinical population studies. However, the tensor distribution function (TDF) may be used to model multiple underlying fibers by representing the diffusion profile as a probabilistic mixture of tensors. METHODS: We compared the ability of standard FADTI and TDF-derived FA (FATDF ), calculated from a range of dMRI angular resolutions (41, 30, 15, and 7 gradient directions), to profile WM deficits in 251 individuals from the Alzheimer's Disease Neuroimaging Initiative and to detect associations with 1) Alzheimer's disease diagnosis, 2) Clinical Dementia Rating scores, and 3) average hippocampal volume. RESULTS: Across angular resolutions and statistical tests, FATDF showed larger effect sizes than FADTI , particularly in regions preferentially affected by Alzheimer's disease, and was less susceptible to crossing fiber anomalies. CONCLUSION: The TDF ""corrected"" form of FA may be a more sensitive and accurate alternative to the commonly used FADTI , even in clinical quality dMRI data. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.",Alzheimer's disease;diffusion-weighted imaging;fractional anisotropy;tensor distribution function;white matter,"Nir, T. M.;Jahanshad, N.;Villalon-Reina, J. E.;Isaev, D.;Zavaliangos-Petropulu, A.;Zhan, L.;Leow, A. D.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.;Alzheimer's Diseaase Neuroimaginng, Initiative",2017,Mar 07,,0,
2246,Connectivity network measures predict volumetric atrophy in mild cognitive impairment,"Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global ""small-world"" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian ""expansion factor maps"" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.",aged;Alzheimer disease;article;brain cortex atrophy;brain mapping;clinical article;cognitive defect;connectome;controlled study;diffusion weighted imaging;disease course;disease severity;female;human;image analysis;image processing;longitudinal study;male;neuroimaging;nuclear magnetic resonance imaging;prediction;tractography;volumetry;white matter,"Nir, T. M.;Jahanshad, N.;Toga, A. W.;Bernstein, M. A.;Jack, C. R.;Weiner, M. W.;Thompson, P. M.",2015,,10.1016/j.neurobiolaging.2014.04.038,0,
2247,Connectivity network measures predict volumetric atrophy in mild cognitive impairment,"Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 +/- 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global ""small-world"" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian ""expansion factor maps"" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.",Aged;Alzheimer Disease;Atrophy;Diffusion Magnetic Resonance Imaging/ methods;Disease Progression;Female;Forecasting;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Mild Cognitive Impairment/ pathology/ physiopathology;Nerve Net/pathology/physiopathology;Neural Conduction;Neuroimaging/ methods;White Matter/ pathology/ physiopathology,"Nir, T. M.;Jahanshad, N.;Toga, A. W.;Bernstein, M. A.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.",2015,Jan,10.1016/j.neurobiolaging.2014.04.038,0,
2248,Small World Network Measures Predict White Matter Degeneration in Patients with Early-Stage Mild Cognitive Impairment,"Alzheimer's Disease (AD) has long been considered a cortical degenerative disease, but impaired brain connectivity, due to white matter injury, may exacerbate cognitive problems. Predicting brain changes is critically important for early treatment. In a longitudinal diffusion tensor imaging study, we investigated white matter fiber integrity in 19 patients (mean age: 74.7 +/- 8.4 yrs at baseline) displaying early signs of mild cognitive impairment (eMCI). We first examined whether baseline average fractional anisotropy (FA) measures in the corpus callosum (CC) predicted changes in white matter integrity over the following 6 months. We then examined whether ""small world"" architecture measures - calculated from baseline connectivity maps - predicted white matter changes over the next 6 months. While average CC FA measures at baseline were not associated with future changes in FA, network measures were a sensitive biomarker for predicting white matter changes during this critical time before AD strikes.",,"Nir, T.;Jahanshad, N.;Jack, C. R.;Weiner, M. W.;Toga, A. W.;Thompson, P. M.",2012,,10.1109/isbi.2012.6235831,0,
2249,Executive function assessment in patients with subcortical cerebral infarction using the Trail Making Test and Wisconsin Card Sorting Test,"To assess executive function in patients with subcortical cerebral infarctions, we implemented a Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST). We recruited 19 patients who had subcortical cerebral infarction on magnetic resonance images (MRI). The patients were classified into two categories depending on the degree of deep white matter hyperintensity (DWMH) on MRI. On comparing MRI and pathological findings, the punctate DWMH was not associated with infarction, but large confluent DWMH suggests subcortical ischemia. On this basis, the low grade DWMH group consisted of 12 patients with punctate foci, and seven patients with large confluent areas were classified in the high grade DWMH group. All patients were right-handed and without symptomatic hemiparesis. To exclude demented patients, cognitive function was examined. The vascular lesions were confirmed by brain magnetic resonance angiography and ultrasonography of the carotid arteries, and we excluded patients with severe stenotic or occlusive vascular lesions in cerebral or carotid arteries. On TMT, we analyzed the time required for Part A and Part B, and the difference in time required (required time difference). We also subtracted the time required for Part A form that required for Part B. To exclude the influence of potential hemiparesis, we also calculated the time required ratio expressed as follows; time required for Part B / time required for Part A. There was no significant increase in the time required for Part A, but we found significant increase in the time required for Part B, the required time difference and the required time ratio in the high grade DWMH group. There was no significant difference on WCST. On pathological examination in normal elderly subjects, punctate foci can be found, but not large confluent DWMH. In this study, we found that patients with severe DWMH may have impaired executive functions. These results might be induced by the pathological features of subcortical ischemia.",,"Niiyama, K.;Hasegawa, A.;Kato, H.;Umesato, N.;Utsumi, H.",2008,January,,0,
2250,Usefulness of visual evaluation of the anterior thalamic radiation by diffusion tensor tractography for differentiating between Alzheimer's disease and elderly major depressive disorder patients,"BACKGROUND AND OBJECTIVE: Many surveys of neural integrity of the cerebral white matter with psychiatric diseases on diffusion tensor imaging have recently been performed, but these mainly utilize fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values, and the results were inconsistent and not fully applied clinically. In this study, we investigated the possibility of differentiating between Alzheimer's disease (AD) and elderly major depressive disorder (MDD) patients in whom early-stage symptoms are difficult to diagnose, by visually evaluating cerebral nerve fascicles utilizing diffusion tensor tractography. We also measured and evaluated FA and ADC values at the same time. SUBJECTS AND METHODS: The subjects included 13 AD patients (age: 69.5 +/- 5.1 years), 19 MDD patients (65.8 +/- 5.7 years), and 22 healthy control (HC) subjects (67.4 +/- 4.8 years). Images were acquired using a 1.5T magnetic resonance imaging device and analyzed by diffusion tensor tractography analysis software. RESULTS: Depiction of the anterior thalamic radiation (ATR) tended to be poor in AD patients unlike in MDD patients and HC subjects. The FA values in the left superior longitudinal fasciculus and fornix (FX) in AD patients were significantly different from those in MDD patients and HC subjects. The ADC values in the bilateral ATR and left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX in AD patients were significantly different from those in MDD patients and HC subjects. CONCLUSION: Visual evaluation of the ATR in combination with the FA values of the left superior longitudinal fasciculus and FX and ADC values of the bilateral ATR, left superior and inferior longitudinal fasciculi, left inferior fronto-occipital fasciculus, and FX is useful for differentiating between AD and MDD patients, which further suggests that it may become a useful auxiliary diagnostic tool.",,"Niida, A.;Niida, R.;Kuniyoshi, K.;Motomura, M.;Uechi, A.",2013,,10.2147/ijgm.s42953,0,
2251,Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers,"Apolipoprotein E epsilon4 is a major genetic risk factor for Alzheimer's disease, but the neurobiological basis for this risk is unknown. We used diffusion tensor imaging to measure diffusion anisotropy in the parahippocampal gyrus white matter in healthy elderly apolipoprotein E epsilon4 carriers and noncarriers. We also measured volumes of the lateral ventricles and temporal horns as proxies of cerebral atrophy. The epsilon4 carriers (n=14) showed significantly lower fractional anisotropy and higher radial diffusivity in the parahippocampal white matter 15 mm below the anterior commissure-posterior commissure plane than noncarriers (n=15). No group differences in ventricular volumes were found, nor were diffusion tensor imaging measures modulated by ventricular volumes. Diffusion tensor imaging may be sufficiently sensitive to detect preclinical brain changes related to Alzheimer's disease.","Aged;Anisotropy;Apolipoprotein E4;Apolipoproteins E/ genetics;Brain Mapping/methods;Cerebral Cortex/ abnormalities;Diffusion Magnetic Resonance Imaging/methods;Female;Functional Laterality;Humans;Image Processing, Computer-Assisted/methods;Lateral Ventricles/pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Parahippocampal Gyrus/ pathology;Statistics, Nonparametric","Nierenberg, J.;Pomara, N.;Hoptman, M. J.;Sidtis, J. J.;Ardekani, B. A.;Lim, K. O.",2005,Aug 22,,0,
2252,The Cerebrospinal Fluid Aβ1-42/Aβ1-40 Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer's Disease in a Clinical Setting,"Background: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ1-42/Aβ1-40 ratio is used as compared to CSF Aβ1-42 levels alone. Objective: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer's disease (AD) in a clinical setting. Methods: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [18F]Florbetapir ([18F]AV45) PET scan, [18F]FDG PET scan, MRI scan, and an extensive neuropsychological examination. In a large subset (n = 67), a lumbar puncture was performed and AD biomarkers were analyzed (Aβ1-42, Aβ1-40, T-tau, P-tau181). Results: We detected an increased concordance in the visual and quantitative (standardized uptake value ratio (SUVR) and total volume of distribution (VT)) [18F]AV45 PET measures when the CSF Aβ1-42/Aβ1-40 was applied compared to Aβ1-42 alone. CSF biomarkers were stronger associated to [18F]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matter. Conclusion: The concordance between CSF Aβ and [18F]AV45 PET increases when the CSF Aβ1-42/Aβ1-40 ratio is applied. This finding is of most importance for the biomarker-based diagnosis of AD as well as for selection of subjects for clinical trials with potential disease-modifying therapies for AD.",PET-CT scanner;PrismaFit;Trio;amyloid beta protein[1-40];amyloid beta protein[1-42];av45 f 18;florbetapir f 18;fluorodeoxyglucose f 18;taurine transporter;taurocyamine kinase;tracer;unclassified drug;adult;aged;Alzheimer disease;Apathy Evaluation Scale;article;cerebrospinal fluid;cerebrospinal fluid amyloid beta protein[1-40] ratio;cerebrospinal fluid amyloid beta protein[1-42] ratio;clinical practice;computer assisted tomography;concentration ratio;controlled study;dementia;depression;depression assessment;female;gray matter;human;longitudinal study;lumbar puncture;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;pharmacokinetic parameters;positron emission tomography;priority journal;prospective study;quantitative analysis;volume of distribution;white matter;Biograph mCT,"Niemantsverdriet, E.;Ottoy, J.;Somers, C.;De Roeck, E.;Struyfs, H.;Soetewey, F.;Verhaeghe, J.;Van Den Bossche, T.;Van Mossevelde, S.;Goeman, J.;De Deyn, P. P.;Mariën, P.;Versijpt, J.;Sleegers, K.;Van Broeckhoven, C.;Wyffels, L.;Albert, A.;Ceyssens, S.;Stroobants, S.;Staelens, S.;Bjerke, M.;Engelborghs, S.",2017,,10.3233/jad-170327,0,
2253,"Not only cardiovascular, but also coordinative exercise increases hippocampal volume in older adults","Cardiovascular activity has been shown to be positively associated with grey and white matter volume of, amongst others, frontal and temporal brain regions in older adults. This is particularly true for the hippocampus, a brain structure that plays an important role in learning and memory, and whose decline has been related to the development of Alzheimer's disease. In the current study, we were interested in whether not only cardiovascular activity but also other types of physical activity, i.e., coordination training, were also positively associated with the volume of the hippocampus in older adults. For this purpose we first collected crosssectional data on ""metabolic fitness"" (cardiovascular fitness and muscular strength) and ""motor fitness"" (e.g, balance, movement speed, fine coordination). Second, we performed a 12-month randomized controlled trial. Results revealed that motor fitness but not metabolic fitness was associated with hippocampal volume. After the 12-month intervention period, both, cardiovascular and coordination training led to increases in hippocampal volume. Our findings suggest that a high motor fitness level as well as different types of physical activity were beneficial to diminish age-related hippocampal volume shrinkage or even increase hippocampal volume.",adult;aged;article;brain function;brain metabolism;brain size;cardiovascular performance;controlled study;cross-sectional study;dentate gyrus;episodic memory;exercise;eye hand coordination;female;hippocampus;human;human experiment;left hemisphere;lifespan;male;Mini Mental State Examination;motor activity;motor coordination;motor performance;nervous system development;normal human;nuclear magnetic resonance imaging;physical activity;relaxation training;right hemisphere;spatial learning;spatial memory;spatial orientation;stretching exercise;synaptogenesis;temporal lobe,"Niemann, C.;Godde, B.;Voelcker-Rehage, C.",2014,,,0,
2254,White matter abnormalities on MRI in neuroacanthocytosis,,acanthocytosis;adult;article;case report;chorea;clinical feature;degenerative disease;dementia;electroencephalogram;human;laboratory diagnosis;male;medical examination;neuroacanthocytosis;priority journal;tonic clonic seizure;white matter,"Nicholl, D. J.;Sutton, I.;Dotti, M. T.;Supple, S. G.;Danek, A.;Lawden, M.",2004,,,0,
2255,Aberrant Spontaneous Brain Activity in Patients with Mild Cognitive Impairment and concomitant Lacunar Infarction: A Resting-State Functional MRI Study,"BACKGROUND: Lacunar infarctions (LI) have been associated with a cognitive decline and an increased risk of dementia. Whether and how the pattern of spontaneous brain activity in patients with mild cognitive impairment (MCI) differs in subjects with and without concomitant LI remains unclear. OBJECTIVE: To compare the pattern of spontaneous brain activity in MCI patients with versus those without LI using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Forty-eight MCI patients, including 22 with LI [MCI-LI] and 26 without LI [MCI-no LI], and 28 cognitive normal subjects underwent rs-fMRI post-processed using regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) methods. RESULTS: Compared with cognitively normal subjects, the MCI-LI patients had decreased ReHo in the precuneus/cuneus (Pcu/CU) and insula; decreased ALFF in the Pcu/CU and frontal lobe; and increased ALFF and ReHo in the temporal lobe. While the MCI-no LI group had increased ReHo and ALFF in the bilateral hippocampus and parahippocampal gyrus, frontal lobe, and decreased ALFF and ReHo in the temporal lobe. Compared with the MCI-no LI patients, those with MCI-LI had decreased ALFF in the frontal lobe; decreased ReHo in the Pcu/CU and insula; and increased ALFF and ReHo in the temporal lobe (p < 0.05, AlphaSim corrected). In MCI-LI patients, the MOCA scores showed a relatively weak correlation with ALFF values in the medial frontal gyrus (r = 0.432, p = 0.045) (of borderline significance after Bonferroni correction). CONCLUSIONS: The spontaneous brain activities in MCI-LI were distinct from MCI-no LI. The probable compensatory mechanism observed in MCI-no LI might be disrupted in MCI with LI due to vascular damage.",,"Ni, L.;Liu, R.;Yin, Z.;Zhao, H.;Nedelska, Z.;Hort, J.;Zhou, F.;Wu, W.;Zhang, X.;Li, M.;Yu, H.;Zhu, B.;Xu, Y.;Zhang, B.",2016,Jan 13,10.3233/jad-150622,0,
2256,Cortical localization of microbleeds in cerebral amyloid angiopathy: an ultra high-field 7T MRI study,"The extent of cortical involvement of cerebral amyloid angiopathy (CAA)-related microbleeds (CMBs) remains unclear. We examined five consecutive patients with probable CAA and three non-demented elderly subjects with ultra-high field 7T MRI, to identify the precise location of CAA-related CMBs. In five CAA patients, 169 of a total of 170 lobar CMBs were located in cortical areas on 7T MRI, while a precise cortical versus juxtacortical localization was unable to be determined for 50/76 CMBs observed by conventional MRI. 7T MRI demonstrates that nearly all lobar CMBs are located in cortex in CAA.","Aged;Aged, 80 and over;Cerebral Amyloid Angiopathy/ pathology/physiopathology;Cerebral Hemorrhage/ pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging/instrumentation;Male;Middle Aged","Ni, J.;Auriel, E.;Martinez-Ramirez, S.;Keil, B.;Reed, A. K.;Fotiadis, P.;Gurol, E. M.;Greenberg, S. M.;Viswanathan, A.",2015,,10.3233/jad-140864,0,
2257,Changes of white matter in aging and early Alzheimer's disease by diffusion tensor imaging,"Objective: To investigate the effects of aging and early stage Alzheimer's disease (AD) on white matter (WM) integrity using diffusion tensor imaging (DTI). Methods: DTI was performed with 20 young and middle age subjects (YN), 18 elder subjects (ON) and 14 mildly impaired AD patients. Fractional anisotropy (FA), mean diffusivity (<D>), and three eigenvalues (λ(1), λ(2), and λ(3)) values were computed and compared on 9 regions of interest (ROI). Results: Compared with YN. ON showed that (D), λ(1), λ(2) and λ(3) significantly increased in all ROIs and FA, however, significant decreased only in genu and body (CCM) of corpus callosum (CC). AD patients as compared with old controls, showed significant decrease in FA in the parietal-temporal subcortical WM and the posterior CC (CCP), significant increase in λ(1) in CCM, and significant increase (D) and λ3 in CCP. Conclusion: Results showed robust age-related effects on WM change. AD patients have additional WM alterations. Different DTI indices have different sensitivity in detection of WM integrity.",,"Ni, H. Y.;Wang, M. S.;Voyko, K.;Jianhui, Z.;Qi, J.",2007,July,,0,
2258,Correlation between white matter alterations and cognitive function decline in early Alzheimer's disease,"Objective: To investigate the effects of early stage Alzheimer's disease (AD) on white matter (WM) integrity using diffusion tensor imaging (DTI) and its relationship with cognitive function decline. Methods: DTI was performed in 32 subjects, including 14 early AD patients and 18 elder controls (ON) with a 1.5 T MR scanner. Fractional anisotropy (FA) and mean diffusivity (D̄) values were computed and compared for 9 regions of interest (ROI). Eight standard neuropsychological tests were performed and compared between",,"Ni, H. Y.;Wang, M. S.;Qi, J.",2008,February,,0,
2259,Grey and white matter brain network changes in frontotemporal dementia subtypes,"Background: Frontotemporal dementia (FTD) comprises of three clinical syndromes, behavioural-variant frontotemporal dementia (bvFTD), semantic dementia (SV-PPA), and progressive nonfluent aphasia (NFV-PPA) with unique underlying neuroanatomical deficits. To date, however, grey matter structural differences and their connecting white matter tracts in this network have been mostly characterised in comparison to controls, whereas within FTD subtype comparisons in the same patients have not been explored. Methodology: In 94 participants, including bvFTD (n = 16), SV-PPA (n = 16) and NFV-PPA (n = 16), as well as an age-matched control group (n = 46), we employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to examine grey and white matter key signatures in each of the three FTD subtypes. Results: Our results showed that bvFTD had specific ventromedial prefrontal cortex and striatum grey matter atrophy along with their connecting white matter tracts compared to other FTD subtypes. By contrast",,"Nguyen, T.;Bertoux, M.;O'Callaghan, C.;Ahmed, S.;Hodges, J. R.;Hornberger, M.",2013,December,,0,
2260,Use of lacunar infarction as a marker of small vessel disease,,brain damage;brain hemorrhage;cerebrovascular disease;dementia;disease association;disease marker;human;lacunar stroke;letter;neuroimaging;nuclear magnetic resonance imaging;pathogenesis;priority journal,"Ng, M.;Singh, P.",2015,,,0,
2261,Role of cognitive enhancer therapy in Alzheimer's disease with concomitant cerebral white matter disease: findings from a long-term naturalistic study,"BACKGROUND: Evidence is lacking for cognitive enhancer therapy in patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as such patients would have been excluded from clinical trials. Earlier studies of mixed AD have focused on large vessel cerebrovascular disease. The influence of small vessel cerebrovascular disease (svCVD) in the form of white matter hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed. OBJECTIVE: In this long-term naturalistic study, we evaluated the effectiveness of cognitive enhancers in patients with mixed AD with svCVD. METHODS: We conducted a retrospective analysis of a prospective clinical database from a memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as a marker of svCVD. Demographic, cognitive, and treatment data were analysed. Linear mixed models with patient-specific random effects were used to evaluate cognitive outcomes over time while adjusting for confounders. RESULTS: Patients with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over a median duration of 28.7 months. Patients with mixed AD had a higher prevalence of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores decreased over time (-0.04, p = 0.007), and the decrease was similar for both diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84 for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72 and 0.48 for pure AD and mixed AD, respectively. CONCLUSION: Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD with svCVD. These findings would need to be confirmed in randomized clinical trials.","Aged;Aged, 80 and over;Alzheimer Disease/ drug therapy/physiopathology;Cerebrovascular Disorders/ drug therapy/etiology;Cognition Disorders/ drug therapy/etiology;Databases, Factual;Female;Follow-Up Studies;Humans;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Nootropic Agents/ pharmacology;Retrospective Studies;Time Factors;White Matter/pathology","Ng, K. P.;Ng, A.;Assam, P.;Heng, E.;Kandiah, N.",2014,Sep,10.1007/s40268-014-0057-5,0,
2262,In-vivo investigation of the human cingulum bundle using the optimization of MR diffusion spectrum imaging,"Diffusion spectrum imaging (DSI) is a generalization of diffusion tensor imaging to map fibrous structure of white matter and potentially very sensitive to alterations of the cingulum bundles in dementia. In this in-vivo 4T study, DSI parameters especially spatial resolution and diffusion encoding bandwidth were optimized on humans to segment the cingulum bundles for tract level measurements of diffusion. The careful tailoring of the DSI acquisitions in conjunction with fiber tracking provided an optimal DSI setting for a reliable quantification of the cingulum bundle tracts. The optimization of tracking the cingulum bundle was verified using fiber tract quantifications, including coefficients of variability of DSI measurements along the fibers between and within healthy subjects in back-to-back studies and variogram analysis of spatial correlations between diffusion orientation distribution functions (ODF) along the cingulum bundle tracts. The results demonstrate that the identification of the cingulum bundle in human brain is reproducible using an optimized DSI parameter for maximum b-value and high spatial resolution of the DSI acquisition with a feasible acquisition time of whole brain in clinical practice. This optimized DSI setting should be useful for detecting alterations along the cingulum bundle in Alzheimer disease and related neurodegenerative disorders.","Adult;Algorithms;Diffusion Tensor Imaging/ methods;Female;Gyrus Cinguli/ anatomy & histology;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Male;Nerve Fibers/ ultrastructure;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Young Adult","Nezamzadeh, M.;Wedeen, V. J.;Wang, R.;Zhang, Y.;Zhan, W.;Young, K.;Meyerhoff, D. J.;Weiner, M. W.;Schuff, N.",2010,Jul,10.1016/j.ejrad.2009.06.019,0,
2263,Progressive Multifocal Leukoencephalopathy Presenting as Multiple Enhancing Lesions on MRI: Case Report and Literature Review,"This report describes an immunocompetent patient with memory loss and motor abnormalities whose magnetic resonance images demonstrated multiple enhancing white matter lesions, including one that was cystic, suggestive of metastatic tumors or abscesses. Neuropathological evaluation at biopsy and subsequent autopsy revealed progressive multifocalleukoencephalopathy. Magnetic resonance evidence of enhancement and cystic changes are rare findings in progressive multifocal leukoencephalopathy, but should be considered in the differential diagnosis, especially in patients without evidence for primary malignancy or infection.",,"Newton, H. B.;Makley, M.;Slivka, A. P.;Li, J.",1995,1995,,0,
2264,Impact and integration of clinical computerized axial tomography and surface EEG's,"The impact of computerized axial tomography (CT scan) in a referral hospital resulted initially in decreased use of the EEG, followed by return toward the expected gain in number of EEG procedures. This probably reflects recognition of the complimentary anatomical and physiological bases as indicated by selected supratentorial (e.g. early cerebral infarctions, diffuse cerebral carcinomatoses) and infratentorial (brainstem gliomas, hemorrhages, infarctions) lesions with normal CT scans and an abnormal EEG. Gross cerebral cortical atrophy, ventricular enlargement, and space occupying lesions revealed significant, but inconstant relationships to EEG features of: (1) background frequency and voltage, (2) nonparoxysmal slow wave transients (theta, theta delta, and serial rhythmic/irregular delta activity), (3) nonspecific activity (bursts, sharp waves, and (4) specific (spikes, spike wave) paroxysmal discharges. In uncomplicated series of (1) senile and presenile dementias, (2) single major supratentorial vascular infarctions and (3) single intracranial neoplasms, the EEG and CT scan findings have been compared. The EEG demonstrated objective abnormalities in primary neurophysiological disorders (closed head injuries, toxic metabolic disturbances, meningo encephalitides, and seizures) with greater frequency than the CT scan. Anatomical imaging by pneumoencephalography, pancerebral angiography, and radionucleide scanning may be replaced by CT scan, but the EEG will not likely be reduced to a 'screening tool for patients with neurological complaints other than seizure disorders.",,"Newman, S. E.",1977,1977,,0,
2265,Methodological improvements in voxel-based analysis of diffusion tensor images: applications to study the impact of apolipoprotein E on white matter integrity,"PURPOSE: To identify regional differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) using customized preprocessing before voxel-based analysis (VBA) in 14 normal subjects with the specific genes that decrease (apolipoprotein [APO] E epsilon2) and that increase (APOE epsilon4) the risk of Alzheimer's disease. MATERIALS AND METHODS: Diffusion tensor images (DTI) acquired at 1.5 Tesla were denoised with a total variation tensor regularization algorithm before affine and nonlinear registration to generate a common reference frame for the image volumes of all subjects. Anisotropic and isotropic smoothing with varying kernel sizes was applied to the aligned data before VBA to determine regional differences between cohorts segregated by allele status. RESULTS: VBA on the denoised tensor data identified regions of reduced FA in APOE epsilon4 compared with the APOE epsilon2 healthy older carriers. The most consistent results were obtained using the denoised tensor and anisotropic smoothing before statistical testing. In contrast, isotropic smoothing identified regional differences for small filter sizes alone, emphasizing that this method introduces bias in FA values for higher kernel sizes. CONCLUSION: Voxel-based DTI analysis can be performed on low signal to noise ratio images to detect subtle regional differences in cohorts using the proposed preprocessing techniques.","Aged;Algorithms;Anisotropy;Apolipoproteins E/ metabolism;Brain/ metabolism/ ultrastructure;Diffusion Tensor Imaging/ methods;Female;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/methods;Imaging, Three-Dimensional/methods;Male;Nerve Fibers, Myelinated/ metabolism/ ultrastructure;Reproducibility of Results;Sensitivity and Specificity","Newlander, S. M.;Chu, A.;Sinha, U. S.;Lu, P. H.;Bartzokis, G.",2014,Feb,10.1002/jmri.24157,0,
2266,Dynamic Changes in White Matter Abnormalities Correlate with Late Improvement and Deterioration Following TBI: A Diffusion Tensor Imaging Study,"Objective. Traumatic brain injury (TBI) is not a single insult with monophasic resolution, but a chronic disease, with dynamic processes that remain active for years. We aimed to assess patient trajectories over the entire disease narrative, from ictus to late outcome. Methods. Twelve patients with moderate-to-severe TBI underwent magnetic resonance imaging in the acute phase (within 1 week of injury) and twice in the chronic phase of injury (median 7 and 21 months), with some undergoing imaging at up to 2 additional time points. Longitudinal imaging changes were assessed using structural volumetry, deterministic tractography, voxel-based diffusion tensor analysis, and region of interest analyses (including corpus callosum, parasagittal white matter, and thalamus). Imaging changes were related to behavior. Results. Changes in structural volumes, fractional anisotropy, and mean diffusivity continued for months to years postictus. Changes in diffusion tensor imaging were driven by increases in both axial and radial diffusivity except for the earliest time point, and were associated with changes in reaction time and performance in a visual memory and learning task (paired associates learning). Dynamic structural changes after TBI can be detected using diffusion tensor imaging and could explain changes in behavior. Conclusions. These data can provide further insight into early and late pathophysiology, and begin to provide a framework that allows magnetic resonance imaging to be used as an imaging biomarker of therapy response. Knowledge of the temporal pattern of changes in TBI patient populations also provides a contextual framework for assessing imaging changes in individuals at any given time point.",,"Newcombe, V. F. J.;Correia, M. M.;Ledig, C.;Abate, M. G.;Outtrim, J. G.;Chatfield, D. O. R. I. S.;Geeraerts, T.;Manktelow, A. E.;Garyfallidis, E.;Pickard, J. D.;Sahakian, B. J.;Hutchinson, P. J. A.;Rueckert, D.;Coles, J. P.;Williams, G. B.;Menon, D. K.",2016,1,,0,
2267,Frequency and topographical distribution of CD68-positive macrophages and HIV-1 core proteins in HIV-associated brain lesions,"We report the neuropathological and immunohistochemical findings in the brains of 14 AIDS patients with HIV-related encephalopathy. Clinically, half of the patients presented with severe AIDS dementia complex including advanced psychomotor retardation and behavioural dysfunction. These features correlated with striking cerebral atrophy and subcortical lesions visible in CT and/or MRI scans. In 7 cases early signs of impaired memory and concentration and/or psychomotor slowing were apparent accompanied by subcortical lesions in MRI scans and normal CCTs. In order to investigate the topographical distribution of HIV-1-associated features, in every case tissue samples from the frontal, temporal, parietal, occipital cortex and subcortical white matter, the hippocampus, basal ganglia, midbrain, pons, medulla oblongata and cerebellum were studied. In all patients histological examination disclosed the typical cellular constituents of HIV encephalitis (n = 12) or leukoencephalopathy (n = 2). Antibodies against lymphocyte subsets, CD68 antigen, myelin basic protein and GFAP were used to characterize the phenotype of cells and to highlight the white matter gliosis. The distribution and degree of pathological features were analysed in a semiquantitative scale, based on the number of CD68-positive cells, and disclosed great interindividual differences concerning the affected brain regions which only in part correlated with the severity of the clinical picture. It is noteworthy, that the deep gray matter, in particular putamen and thalamus, was involved in every case, independent from the stage of the disease. In addition, quantity and topographical distribution of HIV-1 core protein p24 were studied by use of two monoclonal antibodies. It is noteworthy, that the number of immunoreactive multinucleated giant cells and microglial cells decreased gradually from the deep gray matter, especially putamen and thalamus, and deep white matter to corpus callosum, cerebellar white matter and subcortical cerebral white matter. The topographical predilection of the deep gray matter even in cases with early cognitive decline indicates that the basal ganglia are affected early in the course of the disease. This observation closely resembles the results of highly sensitive quantitative neuropsychological tests which disclosed slowing and impaired coordination of rapid extremity movements indicating basal ganglia lesions even in early stages of HIV dementia.","AIDS Dementia Complex/*immunology/*pathology;Antigens, CD/*analysis;Antigens, Differentiation, Myelomonocytic/*analysis;HIV Core Protein p24/*analysis;*Hiv-1;Humans;Macrophages/chemistry/*pathology","Neuen-Jacob, E.;Arendt, G.;Wendtland, B.;Jacob, B.;Schneeweis, M.;Wechsler, W.",1993,Nov-Dec,,0,
2268,Subgroup of ADNI normal controls characterized by atrophy and cognitive decline associated with vascular damage,"Previous work examining Alzheimer's Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey's Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings.","Aged;Aged, 80 and over;Aging/ pathology/physiology;Alzheimer Disease/blood/cerebrospinal fluid/pathology;Atrophy;Biomarkers/blood/cerebrospinal fluid/metabolism;Brain/ pathology/physiopathology;Cerebrovascular Disorders/complications/ pathology/physiopathology;Cognition Disorders/etiology/ pathology/physiopathology;Female;Humans;Male;Registries","Nettiksimmons, J.;Beckett, L.;Schwarz, C.;Carmichael, O.;Fletcher, E.;Decarli, C.",2013,Mar,10.1037/a0031063,0,
2269,Small vessel disease is linked to disrupted structural network covariance in Alzheimer's disease,"INTRODUCTION: Cerebral small vessel disease (SVD) is thought to contribute to Alzheimer's disease (AD) through abnormalities in white matter networks. Gray matter (GM) hub covariance networks share only partial overlap with white matter connectivity, and their relationship with SVD has not been examined in AD. METHODS: We developed a multivariate analytical pipeline to elucidate the cortical GM thickness systems that covary with major network hubs and assessed whether SVD and neurodegenerative pathologic markers were associated with attenuated covariance network integrity in mild AD and normal elderly control subjects. RESULTS: SVD burden was associated with reduced posterior cingulate corticocortical GM network integrity and subneocorticocortical hub network integrity in AD. DISCUSSION: These findings provide evidence that SVD is linked to the selective disruption of cortical hub GM networks in AD brains and point to the need to consider GM hub covariance networks when assessing network disruption in mixed disease.",Alzheimer's disease;Cortical thickness;Hippocampal volume;Magnetic resonance imaging;Partial least squares;Rich-Club network;Shape analysis;Small vessel disease;Structural covariance networks;White matter hyperintensity,"Nestor, S. M.;Misic, B.;Ramirez, J.;Zhao, J.;Graham, S. J.;Verhoeff, N. P.;Stuss, D. T.;Masellis, M.;Black, S. E.",2017,Jan 27,,0,
2270,Small vessel disease is linked to disrupted structural network covariance in Alzheimer's disease,"INTRODUCTION: Cerebral small vessel disease (SVD) is thought to contribute to Alzheimer's disease (AD) through abnormalities in white matter networks. Gray matter (GM) hub covariance networks share only partial overlap with white matter connectivity, and their relationship with SVD has not been examined in AD. METHODS: We developed a multivariate analytical pipeline to elucidate the cortical GM thickness systems that covary with major network hubs and assessed whether SVD and neurodegenerative pathologic markers were associated with attenuated covariance network integrity in mild AD and normal elderly control subjects. RESULTS: SVD burden was associated with reduced posterior cingulate corticocortical GM network integrity and subneocorticocortical hub network integrity in AD. DISCUSSION: These findings provide evidence that SVD is linked to the selective disruption of cortical hub GM networks in AD brains and point to the need to consider GM hub covariance networks when assessing network disruption in mixed disease.","Aged;Alzheimer Disease/diagnostic imaging/ pathology;Brain/pathology;Cerebral Small Vessel Diseases/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Neural Pathways/ pathology;Prospective Studies;White Matter;Alzheimer's disease;Cortical thickness;Hippocampal volume;Magnetic resonance imaging;Partial least squares;Rich-Club network;Shape analysis;Small vessel disease;Structural covariance networks;White matter hyperintensity","Nestor, S. M.;Misic, B.;Ramirez, J.;Zhao, J.;Graham, S. J.;Verhoeff, Nplg;Stuss, D. T.;Masellis, M.;Black, S. E.",2017,Jul,,0,
2271,A direct morphometric comparison of five labeling protocols for multi-atlas driven automatic segmentation of the hippocampus in Alzheimer's disease,"Hippocampal volumetry derived from structural MRI is increasingly used to delineate regions of interest for functional measurements, assess efficacy in therapeutic trials of Alzheimer's disease (AD) and has been endorsed by the new AD diagnostic guidelines as a radiological marker of disease progression. Unfortunately, morphological heterogeneity in AD can prevent accurate demarcation of the hippocampus. Recent developments in automated volumetry commonly use multi-template fusion driven by expert manual labels, enabling highly accurate and reproducible segmentation in disease and healthy subjects. However, there are several protocols to define the hippocampus anatomically in vivo, and the method used to generate atlases may impact automatic accuracy and sensitivity - particularly in pathologically heterogeneous samples. Here we report a fully automated segmentation technique that provides a robust platform to directly evaluate both technical and biomarker performance in AD among anatomically unique labeling protocols. For the first time we test head-to-head the performance of five common hippocampal labeling protocols for multi-atlas based segmentation, using both the Sunnybrook Longitudinal Dementia Study and the entire Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) baseline and 24-month dataset. We based these atlas libraries on the protocols of (Haller et al., 1997; Killiany et al., 1993; Malykhin et al., 2007; Pantel et al., 2000; Pruessner et al., 2000), and a single operator performed all manual tracings to generate de facto ""ground truth"" labels. All methods distinguished between normal elders, mild cognitive impairment (MCI), and AD in the expected directions, and showed comparable correlations with measures of episodic memory performance. Only more inclusive protocols distinguished between stable MCI and MCI-to-AD converters, and had slightly better associations with episodic memory. Moreover, we demonstrate that protocols including more posterior anatomy and dorsal white matter compartments furnish the best voxel-overlap accuracies (Dice Similarity Coefficient=0.87-0.89), compared to expert manual tracings, and achieve the smallest sample sizes required to power clinical trials in MCI and AD. The greatest distribution of errors was localized to the caudal hippocampus and the alveus-fimbria compartment when these regions were excluded. The definition of the medial body did not significantly alter accuracy among more comprehensive protocols. Voxel-overlap accuracies between automatic and manual labels were lower for the more pathologically heterogeneous Sunnybrook study in comparison to the ADNI-1 sample. Finally, accuracy among protocols appears to significantly differ the most in AD subjects compared to MCI and normal elders. Together, these results suggest that selection of a candidate protocol for fully automatic multi-template based segmentation in AD can influence both segmentation accuracy when compared to expert manual labels and performance as a biomarker in MCI and AD.","Aged;Alzheimer Disease/*pathology;Databases, Factual;Female;Hippocampus/*pathology;Humans;Image Interpretation, Computer-Assisted/*methods;Magnetic Resonance Imaging;Male;Middle Aged;Alzheimer's disease;Automatic hippocampal segmentation;Hippocampal tracing protocol;Multi-atlas","Nestor, S. M.;Gibson, E.;Gao, F. Q.;Kiss, A.;Black, S. E.",2013,Feb 1,10.1016/j.neuroimage.2012.10.081,0,
2272,Insight on AV-45 binding in white and grey matter from histogram analysis: a study on early Alzheimer's disease patients and healthy subjects,"PURPOSE: AV-45 amyloid biomarker is known to show uptake in white matter in patients with Alzheimer's disease (AD), but also in the healthy population. This binding, thought to be of a non-specific lipophilic nature, has not yet been investigated. The aim of this study was to determine the differential pattern of AV-45 binding in white matter in healthy and pathological populations. METHODS: We recruited 24 patients presenting with AD at an early stage and 17 matched, healthy subjects. We used an optimized positron emission tomography-magnetic resonance imaging (PET-MRI) registration method and an approach based on an intensity histogram using several indices. We compared the results of the intensity histogram analyses with a more canonical approach based on target-to-cerebellum Standard Uptake Value (SUVr) in white and grey matter using MANOVA and discriminant analyses. A cluster analysis on white and grey matter histograms was also performed. RESULTS: White matter histogram analysis revealed significant differences between AD and healthy subjects, which were not revealed by SUVr analysis. However, white matter histograms were not decisive to discriminate groups, and indices based on grey matter only showed better discriminative power than SUVr. The cluster analysis divided our sample into two clusters, showing different uptakes in grey, but also in white matter. CONCLUSION: These results demonstrate that AV-45 binding in white matter conveys subtle information not detectable using the SUVr approach. Although it is not more efficient than standard SUVr in discriminating AD patients from healthy subjects, this information could reveal white matter modifications.",Aged;Alzheimer Disease/ metabolism/radionuclide imaging;Amyloid/metabolism;Aniline Compounds/ metabolism;Case-Control Studies;Cluster Analysis;Discriminant Analysis;Ethylene Glycols/ metabolism;Female;Gray Matter/ metabolism/radionuclide imaging;Humans;Male;Positron-Emission Tomography;Protein Binding;White Matter/ metabolism/radionuclide imaging,"Nemmi, F.;Saint-Aubert, L.;Adel, D.;Salabert, A. S.;Pariente, J.;Barbeau, E. J.;Payoux, P.;Peran, P.",2014,Jul,10.1007/s00259-014-2728-4,0,
2273,Computed tomography in patients presenting with lacunar syndromes,"Of 312 stroke patients who had a CT scan, 37 had presented clinically with a lacunar syndrome. In 18 of the 37, lacunar sized infarcts were demonstrated on the scan, 13 had normal scans and in 6 large infarcts were found. Of these 6, 5 had a pure motor hemiplegia and 1 a pure sensory stroke. Clinical evidence and angiography revealed a potential and treatable source of emboli in both the lacunar sized and the large infarcts. Two conclusions are drawn: a clinical lacunar syndrome may be associated with a large infarct; demonstration of a lacunar infarct on CT scan does not exclude the need for angiography in appropriate cases to discover a possible source of emboli.",brain angiography;central nervous system;cerebrovascular accident;computer analysis;computer assisted tomography;dementia;diagnosis;major clinical study;peripheral vascular system,"Nelson, R. F.;Pullicino, P.;Kendall, B. E.;Marshall, J.",1980,,,0,
2274,Rationale for a trial of low-dose aspirin for the primary prevention of major adverse cardiovascular events and vascular dementia in the elderly: Aspirin in Reducing Events in the Elderly (ASPREE),"Low-dose aspirin (acetylsalicylic acid) therapy has been shown to reduce the risk of vascular events and there is increasing evidence of its potential to reduce the rate of cognitive decline in the elderly. Adverse effects including gastrointestinal and intracranial haemorrhage may offset these benefits. The balance of risks versus benefits of aspirin for the primary prevention of cardiovascular disease and vascular dementia has not been established in the elderly. There is clearly a need to conduct a study in family practice to investigate whether routine use of low-dose aspirin for the primary prevention of cardiovascular disease and vascular dementia in the elderly is beneficial or harmful. Aspirin in reducing events in the elderly (ASPREE) is a placebo-controlled trial of low-dose aspirin for the primary prevention of major adverse cardiovascular events and vascular dementia. It will follow 15,000 subjects aged 70 years or more for an average of 5 years. This sample size has a power of 87% to detect a 15% reduction in primary events in the aspirin group, with an anticipated combined primary event rate of 20 per 1000 patient years.","Aspirin [administration & dosage] [adverse effects] [therapeutic use];Cardiovascular Diseases [mortality] [prevention & control];Dementia, Vascular [mortality] [prevention & control];Double-Blind Method;Platelet Aggregation Inhibitors [administration & dosage] [adverse effects] [therapeutic use];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];aged;article;brain hemorrhage/si [Side Effect];cardiovascular disease/dt [Drug Therapy];cardiovascular disease/pc [Prevention];clinical trial;computer assisted tomography;controlled clinical trial;controlled study;gastrointestinal hemorrhage/si [Side Effect];heart infarction/dt [Drug Therapy];heart infarction/pc [Prevention];human;meta analysis;multiinfarct dementia/dt [Drug Therapy];multiinfarct dementia/pc [Prevention];nuclear magnetic resonance imaging;primary prevention;priority journal;quality of life;randomized controlled trial;stroke/dt [Drug Therapy];stroke/pc [Prevention];subarachnoid hemorrhage/di [Diagnosis];subarachnoid hemorrhage/si [Side Effect];subdural hematoma/di [Diagnosis];subdural hematoma/si [Side Effect];acetylsalicylic acid/ae [Adverse Drug Reaction];acetylsalicylic acid/ct [Clinical Trial];acetylsalicylic acid/do [Drug Dose];acetylsalicylic acid/dt [Drug Therapy];hemoglobin/ec [Endogenous Compound];nonsteroid antiinflammatory agent/dt [Drug Therapy];prostaglandin synthase/ec [Endogenous Compound];Sr-vasc","Nelson, M.;Reid, C.;Beilin, L.;Donnan, G.;Johnston, C.;Krum, H.;Storey, E.;Tonkin, A.;McNeil, J.",2003,,,0,
2275,Phase 1 study of the Pittsburgh compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease,"UNLABELLED: (11)C-Pittsburgh compound B (PiB) marks Abeta amyloidosis, a key pathogenetic process in Alzheimer disease (AD). The use of (11)C-PiB is limited to centers with a cyclotron. Development of the (18)F-labeled thioflavin derivative of PiB, (18)F-flutemetamol, could hugely increase the availability of this new technology. The aims of this phase 1 study were to perform brain kinetic modeling of (18)F-flutemetamol, optimize the image acquisition procedure, and compare methods of analysis (step 1) and to compare (18)F-flutemetamol brain retention in AD patients versus healthy controls in a proof-of-concept study (steps 1 and 2). METHODS: In step 1, 3 AD patients (Mini-Mental State Examination, 22-24) and 3 elderly healthy controls were scanned dynamically during windows of 0-90, 150-180, and 220-250 min after injection of approximately 180 MBq of (18)F-flutemetamol, with arterial sampling. We compared different analysis methods (compartmental modeling, Logan graphical analysis, and standardized uptake value ratios) and determined the optimal acquisition window for step 2. In step 2, 5 AD patients (Mini-Mental State Examination, 20-26) and 5 elderly healthy controls were scanned from 80 to 170 min after injection. To determine overall efficacy, steps 1 and 2 were pooled and standardized uptake value ratios were calculated using cerebellar cortex as a reference region. RESULTS: No adverse events were reported. There was a strong correlation between uptake values obtained with the different analysis methods. From 80 min after injection onward, the ratio of neocortical to cerebellar uptake was maximal and only marginally affected by scan start time or duration. AD patients showed significantly increased standardized uptake value ratios in neocortical association zones and striatum, compared with healthy controls, whereas uptake in white matter, cerebellum, and pons did not differ between groups. Two AD patients were (18)F-flutemetamol-negative and 1 healthy control was (18)F-flutemetamol-positive. CONCLUSION: (18)F-flutemetamol uptake can be readily quantified. This phase 1 study warrants further studies to validate this (18)F-labeled derivative of PiB as a biomarker for Abeta amyloidosis.",Alzheimer Disease [metabolism] [radionuclide imaging];Aniline Compounds [adverse effects] [pharmacokinetics];Benzothiazoles [adverse effects] [pharmacokinetics];Brain [metabolism] [radionuclide imaging];Metabolic Clearance Rate;Radiopharmaceuticals [adverse effects] [pharmacokinetics];Reference Values;Thiazoles [adverse effects] [pharmacokinetics];Tissue Distribution;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword],"Nelissen, N.;Laere, K.;Thurfjell, L.;Owenius, R.;Vandenbulcke, M.;Koole, M.;Bormans, G.;Brooks, D. J.;Vandenberghe, R.",2009,,10.2967/jnumed.109.063305,0,
2276,Neuro-cognitive mechanisms of simultanagnosia in patients with posterior cortical atrophy,"Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas. To test these distinct hypotheses, we investigated a group of 12 patients suffering from posterior cortical atrophy with homogenous lesion sides in parieto-occipital cortices and varying severity of grey and white matter loss. More specifically, we (i) tested whether impaired short-term memory capacity or processing speed underlie symptoms of simultanagnosia; (ii) assessed the link to grey and white matter damage; and (iii) integrated those findings into a neuro-cognitive model of simultanagnosia in patients with posterior cortical atrophy. To this end, simultaneous perception of multiple visual objects was tested in patients with posterior cortical atrophy mostly with positive Alzheimer's disease biomarkers and healthy age-matched controls. Critical outcome measures were identification of overlapping relative to non-overlapping figures and visuo-spatial performance in tests sensitive to simultanagnosia. Using whole report of briefly presented letter arrays based on the mathematically formulated 'Theory of Visual Attention', we furthermore quantified parameters of visual short-term memory capacity and visual processing speed. Grey and white matter atrophy was assessed by voxel-based morphometry analyses of structural magnetic resonance data. All patients showed severe deficits of simultaneous perception. Compared to controls, we observed a specific slowing of visual processing speed, while visual short-term memory capacity was preserved. In a regression analysis, processing speed was identified as the only significant predictor of simultaneous perception deficits that explained a high degree of variance (70-82%) across simultanagnosia tasks. More severe slowing was also indicative for more severe impairments in reading and scene comprehension. Voxel-based morphometry yielded extensive reductions of grey and white matter in parietooccipital and thalamic brain areas. Importantly, the degree of individual atrophy of white matter in left superior parietal lobe, but not of any grey matter region, was associated with processing speed. Based on these findings, we propose that atrophy of white matter commonly observed in posterior cortical atrophy leads to slowing of visual processing speed, which underlies the overt clinical symptoms of simultanagnosia.",biological marker;adult;aged;agnosia;Alzheimer disease;article;attention;brain atrophy;brain cortex atrophy;brain size;clinical article;cognition;comprehension;controlled study;daily life activity;disease severity;female;frontal lobe;gray matter;human;insula;male;middle aged;neuroanatomy;nuclear magnetic resonance imaging;parietal lobe;perceptive threshold;priority journal;reading;short term memory;simultanagnosia;superior longitudinal fasciculus;temporal lobe;thalamus;vision;visual attention;voxel based morphometry;white matter injury,"Neitzel, J.;Ortner, M.;Haupt, M.;Redel, P.;Grimmer, T.;Yakushev, I.;Drzezga, A.;Bublak, P.;Preul, C.;Sorg, C.;Finke, K.",2016,,10.1093/brain/aww235,0,
2277,White matter integrity in dementia with Lewy bodies: a voxel-based analysis of diffusion tensor imaging,"Many patients with dementia with Lewy bodies (DLB) have overlapping Alzheimer's disease (AD)-related pathology, which may contribute to white matter (WM) diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients with DLB (n = 30), age- and sex-matched AD patients (n = 30), and cognitively normal controls (n = 60) were recruited. All subjects underwent DTI, 18F 2-fluoro-deoxy-d-glucose, and (11)C Pittsburgh compound B positron emission tomography scans. DLB patients had reduced fractional anisotropy (FA) in the parietooccipital WM but not elsewhere compared with cognitively normal controls, and elevated FA in parahippocampal WM compared with AD patients, which persisted after controlling for beta-amyloid load in DLB. The pattern of WM FA alterations on DTI was consistent with the more diffuse posterior parietal and occipital glucose hypometabolism of 2-fluoro-deoxy-d-glucose positron emission tomography in the cortex. DLB is characterized by a loss of parietooccipital WM integrity, independent of concomitant AD-related beta-amyloid load. Cortical glucose hypometabolism accompanies WM FA alterations with a concordant pattern of gray and WM involvement in the parietooccipital lobes in DLB.",Aged;Amyloid beta-Peptides/metabolism;Anisotropy;Diffusion Tensor Imaging/ methods;Female;Glucose/metabolism;Humans;Lewy Body Disease/metabolism/ pathology/radionuclide imaging;Male;Middle Aged;Occipital Lobe/metabolism;Positron-Emission Tomography;White Matter/ pathology,"Nedelska, Z.;Schwarz, C. G.;Boeve, B. F.;Lowe, V. J.;Reid, R. I.;Przybelski, S. A.;Lesnick, T. G.;Gunter, J. L.;Senjem, M. L.;Ferman, T. J.;Smith, G. E.;Geda, Y. E.;Knopman, D. S.;Petersen, R. C.;Jack, C. R., Jr.;Kantarci, K.",2015,Jun,10.1016/j.neurobiolaging.2015.03.007,0,
2278,Cognitive aging in persons with minimal amyloid-beta and white matter hyperintensities,"Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimer's disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer-PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(-) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(-) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(-). There were no differences in cognitive performance between WMH(+) and WMH(-) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(-) and WMH(-) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency.","Aged;Aged, 80 and over;Aging/*physiology/psychology;Amyloid beta-Peptides/*metabolism;Brain/*metabolism/radionuclide imaging;Brain Mapping;Cognition/*physiology;Female;Humans;Male;Nerve Fibers, Myelinated/*metabolism/radionuclide imaging;Neuroimaging;Neuropsychological Tests;Amyloid;Cognition;Normal aging;White matter hyperintensities","Nebes, R. D.;Snitz, B. E.;Cohen, A. D.;Aizenstein, H. J.;Saxton, J. A.;Halligan, E. M.;Mathis, C. A.;Price, J. C.;Kamboh, M. I.;Weissfeld, L. A.;Klunk, W. E.",2013,Sep,10.1016/j.neuropsychologia.2013.07.017,0,
2279,Cognitive aging in persons with minimal amyloid-β and white matter hyperintensities,"Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimer's disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer-PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(-) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(-) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(-). There were no differences in cognitive performance between WMH(+) and WMH(-) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(-) and WMH(-) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency. © 2013.",,"Nebes, R. D.;Snitz, B. E.;Cohen, A. D.;Aizenstein, H. J.;Saxton, J. A.;Halligan, E. M.;Mathis, C. A.;Price, J. C.;Kamboh, M.;Weissfeld, L. A.;Klunk, W. E.",2013,September,,0,
2280,Vascular dementia: Why pathology is still important,"Cerebral infarction, as the result of atheroma in large blood vessels, was one of the first explanations for dementia in older people. However, this was a relatively uncommon finding in those presenting with dementia and it was soon realized that subcortical infarctions due to non-atheromatous changes in small blood vessel walls were more important factors in cognitive decline. Furthermore, small vessel disease (SVD) producing lacunar infarcts (LI) and white matter changes increased dementia severity in individuals with only moderate Alzheimer's disease (AD) pathology. Magnetic resonance imaging (MRI) found subcortical (lacunar) 'silent infarcts' and white matter changes were surrogate markers for SVD and increased significantly the likelihood of developing dementia. Detailed histopathological studies of SVD showed it was in fact a range of pathologies, but the aetiology of the most common type (arteriosclerosis/lipohyalinosis) is difficult to explain. Theories to explain SVD include effects of hypertension, a leaky blood-brain barrier (BBB), amyloid accumulation, microbleeds, venous changes and endothelial inflammation. Endothelial expressed inflammatory molecules could represent potential biomarkers of SVD. Many of the risk factors associated with SVD are also present in AD, such as diabetes, systemic hypertension and ageing; all of these can target the endothelium with the potential to initiate SVD, resulting in ischaemic changes and neurodegeneration, including AD pathology. © 2011 Cambridge University Press.",,"Neal, J.",2012,February,,0,
2281,Superficial white matter as a novel substrate of age-related cognitive decline,"Studies of diffusion tensor imaging have focused mainly on the role of deep white matter tract microstructural abnormalities associated with aging and age-related cognitive decline. However, the potential role of superficial white matter (SWM) in aging and, by extension, cognitive-aging, is less clear. Healthy individuals (n= 141; F/M: 66/75 years) across the adult lifespan (18-86years) underwent diffusion tensor imaging and a battery of cognitive testing. SWM was assessed via a combination of probabilistic tractography and tract-based spatial statistics (TBSS). A widespread inverse relationship of fractional anisotropy (FA) values in SWM with age was observed. SWM-FA adjacent to the precentral gyri was associated with fine-motor-speed, whereas performance in visuomotor-attention/processing speed correlated with SWM-FA in all 4 lobes of the left-hemisphere and in right parieto-occipital SWM-FA (family-wise error corrected p < 0.05). Independent of deep white matter-FA, right frontal and right occipital SWM-FA-mediated age effects on motor-speed and visuomotor-attention/processing speed, respectively. Altogether, our results indicate that SWM-FA contributes uniquely to age-related cognitive performance, and should be considered as a novel biomarker of cognitive-aging.",,"Nazeri, A.;Chakravarty, M. M.;Rajji, T. K.;Felsky, D.;Rotenberg, D. J.;Mason, M.;Xu, L. N.;Lobaugh, N. J.;Mulsant, B. H.;Voineskos, A. N.",2015,1,,0,
2282,"Circulating Progenitor Cells Correlate with Memory, Posterior Cortical Thickness, and Hippocampal Perfusion","BACKGROUND: Bone marrow-derived progenitor cells survey the vasculature and home to sites of tissue injury where they can promote repair and regeneration. It has been hypothesized that these cells may play a protective role neurodegenerative and vascular cognitive impairment. OBJECTIVE: To evaluate progenitor cell levels in older adults with and without mild cognitive impairment (MCI), and to relate circulating levels to memory, brain volume, white matter lesion volume, and cerebral perfusion. METHOD: Thirty-two older adults, free of stroke and cardiovascular disease, were recruited from the community and evaluated for diagnosis of MCI versus cognitively normal (CN). Participants underwent brain MRI and blood samples were taken to quantify progenitor reserve using flow cytometry (CD34+, CD34+CD133+, and CD34+CD133+CD309+ cells). RESULTS: Participants with MCI (n = 10) exhibited depletion of all CPC markers relative to those who were CN (n = 22), after controlling for age, sex, and education. Post-hoc age, sex, and education matched comparisons (n = 10 MCI, n = 10 CN) also revealed the same pattern of results. Depletion of CD34+ cells correlated with memory performance, left posterior cortical thickness, and bilateral hippocampal perfusion. Participants exhibited low levels of vascular risk and white matter lesion burden that did not correlate with progenitor levels. CONCLUSIONS: Circulating progenitor cells are associated with cognitive impairment, memory, cortical atrophy, and hippocampal perfusion. We hypothesize that progenitor depletion contributes to, or is triggered by, cognitive decline and cortical atrophy. Further study of progenitor cell depletion in older adults may benefit efforts to prevent or delay dementia.",Atrophy;cognitive dysfunction;memory;perfusion;stem cells,"Nation, D. A.;Tan, A.;Dutt, S.;McIntosh, E. C.;Yew, B.;Ho, J. K.;Blanken, A. E.;Jang, J. Y.;Rodgers, K. E.;Gaubert, A.",2018,,,0,
2283,"A 59-year-old woman with recurrent convulsive seizures, cerebral infarctions, dementia, and intracranial calcifications","A 59-year-old woman with recurrent seizures and progressive dementia is reported. Her past history and familial history were unremarkable. She became short-tempered at 56 years old(Oct. 1991). She had the first seizure attack and was admitted to a hospital at March 4, 1993, with prolonged disturbance of consciousness and subsequent mental deterioration. Her brain CT showed multiple small calcifications in the subcortical white matter and pons. The laboratory data including blood count, serum chemistry, serological studies and CSF was normal. MRI and digital subtraction angiography of the cranial vessels were unremarkable. There was a decrease in accumulation in the right cerebral hemisphere on 123 IMP SPECT. Despite anti-convulsant therapy, she had recurrent seizures several times, with gradual worsening of her mental state. She had the latest seizure attack and was transferred to Matsusaka Chuo Hospital, on August 29, 1993. After the attack she had been in the apallic state, and died on Nov. 13, 1995. This case was discussed in a neurological CPC. The discussants suggested that the isolated angiitis of the central nervous system caused secondary seizures and cerebral infarctions. Post-mortem examination revealed the CNS findings of vasculitis at various stages calcification or mineralization mainly in the subcortical white matter and pons, massive cerebral infarctions with massive exudate, fresh and old small bleedings and exudate around the inflamed or calcified vessels. The white matter degeneration resembled that of Binswanger leukoencephalopathy. The final pathological diagnosis was isolated angiitis of the central nervous system since there was no inflammatory changes or atherosclerotic change of the blood vessels in the extracranial organs.",iodine 123;adult;article;autopsy;brain calcification;brain infarction;brain vasculitis;case report;computer assisted tomography;consciousness disorder;dementia;digital subtraction angiography;female;histopathology;human;mental deterioration;nuclear magnetic resonance imaging;pons;recurrent disease;seizure;single photon emission computer tomography;white matter,"Narital, Y.;Watanabe, Y.;Matsumura, K.;Matsuyama, M.;Hori, K.;Kuzuhara, S.;Ishihara, A.",2000,,,0,
2284,Elevated plasma homocysteine is associated with increased brain atrophy rates in older subjects with mild hypertension,"We determined using serial MR imaging whether raised plasma homocysteine levels are associated with increased brain atrophy, white matter lesion (WML) progression or incidence of silent brain infarcts (SBIs) in older hypertensive subjects. Brain atrophy rates (0.58 ± 0.48% per year, mean ± SD) were significantly correlated with homocysteine (β = 0.46, p = 0.001 homocysteine; β = 0.44, p = 0.007 homocysteine/folate/B12 models) but not with folate or B12 levels. Progression of WML (0.08 ± 0.16%) was not associated with homocysteine level (B = 0.01, p = 0.29). New SBIs were uncommon. In older hypertensive individuals, plasma homocysteine levels are associated with increased rates of whole-brain atrophy but not WML progression. Copyright © 2011 S. Karger AG, Basel.",,"Narayan, S. K.;Firbank, M. J.;Saxby, B. K.;Stansby, G.;Hansrani, M.;O'Brien, J. T.;Ford, G. A.",2011,July,,0,
2285,"Clinical, familial, and neuroimaging features of CADASIL-like patients","OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL. MATERIALS AND METHODS: We performed NOTCH3 analysis (exons 2-23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for NOTCH3 analysis, was retrospectively applied to NOTCH3-negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL-like. RESULTS: Thirty-four CADASIL-like patients (mean age at onset 57.8 years [52.1-63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (α level <0.05) different in frequency between patients with CADASIL and CADASIL-like patients: a positive family history for stroke at age ≤ 60 years, more frequent in patients with CADASIL, and hypertension, more frequent in CADASIL-like patients. CONCLUSIONS: Our experience highlights the growing number of patients presenting with a high suspicion of a cerebral small vessel disease with an autosomal dominant pattern of inheritance and a phenotype closely similar to that of CADASIL but without NOTCH3 mutations. This group remains to be characterized from the genetic point of view. The role of other genes or NOTCH3 alterations on exons other than 2-23 or introns has to be further assessed.","Notch receptor;NOTCH3 protein, human;brain;CADASIL;complication;female;genetics;human;male;middle aged;neuroimaging;nuclear magnetic resonance imaging;onset age;pathology;phenotype;retrospective study","Nannucci, S.;Pescini, F.;Bertaccini, B.;Bianchi, S.;Ciolli, L.;Valenti, R.;Dotti, M. T.;Federico, A.;Inzitari, D.;Pantoni, L.",2015,,,0,
2286,"Adult-onset Alexander disease with typical ""tadpole"" brainstem atrophy and unusual bilateral basal ganglia involvement: A case report and review of the literature","Background: Alexander disease (ALX) is a rare neurological disorder characterized by white matter degeneration and cytoplasmic inclusions in astrocytes called Rosenthal fibers, labeled by antibodies against glial fibrillary acidic protein (GFAP). Three subtypes are distinguished according to age at onset: infantile (under age 2), juvenile (age 2 to 12) and adult (over age 12). Following the identification of heterozygous mutations in GFAP that cause this disease, cases of adult-onset ALX have been increasingly reported.Case Presentation: We present a 60-year-old Japanese man with an unremarkable past and no family history of ALX. After head trauma in a traffic accident at the age of 46, his character changed, and dementia and dysarthria developed, but he remained independent. Spastic paresis and dysphagia were observed at age 57 and 59, respectively, and worsened progressively. Neurological examination at the age of 60 revealed dementia, pseudobulbar palsy, left-side predominant spastic tetraparesis, axial rigidity, bradykinesia and gaze-evoked nystagmus. Brain MRI showed tadpole-like atrophy of the brainstem, caused by marked atrophy of the medulla oblongata, cervical spinal cord and midbrain tegmentum, with an intact pontine base. Analysis of the GFAP gene revealed a heterozygous missense mutation, c.827G>T, p.R276L, which was already shown to be pathogenic in a case of pathologically proven hereditary adult-onset ALX.Conclusion: The typical tadpole-like appearance of the brainstem is strongly suggestive of adult-onset ALX, and should lead to a genetic investigation of the GFAP gene. The unusual feature of this patient is the symmetrical involvement of the basal ganglia, which is rarely observed in the adult form of the disease. More patients must be examined to confirm, clinically and neuroradiologically, extrapyramidal involvement of the basal ganglia in adult-onset ALX. © 2010 Namekawa et al; licensee BioMed Central Ltd.",glial fibrillary acidic protein;adult;Alexander disease;article;bradykinesia;brain atrophy;brain stem;case report;cervical spinal cord;dementia;dysarthria;dysphagia;extrapyramidal syndrome;head injury;heterozygosity;human;male;medulla oblongata;missense mutation;muscle rigidity;nuclear magnetic resonance imaging;nystagmus;pseudobulbar palsy;quadriplegia;spastic paresis;spinal cord atrophy;tegmentum;traffic accident,"Namekawa, M.;Takiyama, Y.;Honda, J.;Shimazaki, H.;Sakoe, K.;Nakano, I.",2010,,,0,
2287,Late-onset leukoencephalopathy without hypertension in a case of young-adult-onset alopecia and spondylosis: A variant of CARASIL?,"We report herein a 61-year-old man with diffuse leukoencephalopathy, subcortical infarcts and cervical and lumbar spondylosis. Medical history included baldness and lumbar spondylosis at young-adult onset. His parents were consanguineous (cousin). He had been experiencing severe lumbago since 20 years old, with hair loss starting around the same time. He noticed dysarthria and gait disturbance at 59 years old. He was admitted to our hospital at 61 years old with aggravation of gait disturbance. On admission, no abnormalities were evident on physical examination except for diffuse baldness. Neurological findings included mild dementia, bilateral hyperreflexia, paraparesis, right Babinski's sign, and pseudobulbar palsy. Blood pressure was normal. T2-weighted imaging of the brain revealed diffuse high-intensity in the periventricular white matter and subcortical infarcts in the brainstem and bilateral basal ganglia. Marked lumbar deformations were observed on spinal MRI. Clinical features in this case met the criteria for cerebral autosomal recessive arteriopathy with subcortical infarctions and leukoencephalopathy (CARASIL), apart from late onset of cerebral infarction.",,"Nakazato, Y.;Ohkuma, A.;Mizoi, Y.;Tamura, N.;Shimazu, K.",2008,June,,0,
2288,Discrimination of dementia with Lewy bodies from Alzheimer's disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated Lie algebra,"INTRODUCTION: The purpose of this study was to identify brain atrophy specific for dementia with Lewy bodies (DLB) and to evaluate the discriminatory performance of this specific atrophy between DLB and Alzheimer's disease (AD). METHODS: We retrospectively reviewed 60 DLB and 30 AD patients who had undergone 3D T1-weighted MRI. We randomly divided the DLB patients into two equal groups (A and B). First, we obtained a target volume of interest (VOI) for DLB-specific atrophy using correlation analysis of the percentage rate of significant whole white matter (WM) atrophy calculated using the Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) based on statistical parametric mapping 8 (SPM8) plus diffeomorphic anatomic registration through exponentiated Lie algebra, with segmented WM images in group A. We then evaluated the usefulness of this target VOI for discriminating the remaining 30 DLB patients in group B from the 30 AD patients. Z score values in this target VOI obtained from VSRAD were used as the determinant in receiver operating characteristic (ROC) analysis. RESULTS: Specific target VOIs for DLB were determined in the right-side dominant dorsal midbrain, right-side dominant dorsal pons, and bilateral cerebellum. ROC analysis revealed that the target VOI limited to the midbrain exhibited the highest area under the ROC curves of 0.75. CONCLUSIONS: DLB patients showed specific atrophy in the midbrain, pons, and cerebellum. Midbrain atrophy demonstrated the highest power for discriminating DLB and AD. This approach may be useful for determining the contributions of DLB and AD pathologies to the dementia syndrome.","Aged;Algorithms;Alzheimer Disease/ pathology;Brain/ pathology;Data Interpretation, Statistical;Diagnosis, Differential;Diffusion Tensor Imaging/ methods;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Lewy Body Disease/ pathology;Male;Pattern Recognition, Automated/methods;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Nakatsuka, T.;Imabayashi, E.;Matsuda, H.;Sakakibara, R.;Inaoka, T.;Terada, H.",2013,May,10.1007/s00234-013-1138-9,0,
2289,A case of possible neuro-Sweet disease with prolonged disturbance of consciousness and no dermal lesion during the course of dementia,"The patient was a 58-year-old man with 1-year history of cognitive decline, which was diagnosed as Alzheimer's disease in another hospital. He was admitted to our hospital for extreme fatigue, weight loss, and dysphagia, subsequent to the left peripheral facial paresis. Brain magnetic resonance (MR) imaging showed bilateral diffuse white matter lesions and hippocampal atrophy. After admission, he presented with sudden high fever, recurrent exacerbations of consciousness, and increased C-reactive protein level with marked neutrophilia, with the result that he underwent mechanical ventilation. Routine cerebrospinal fluid findings at the exacerbation were normal i.e. 4.7 cells/mm(3), 40 mg/dl of protein, but IL-6 concentration was mildly elevated to 22.2 pg/ml. After confirming the positivity of HLA (human leukocyte antigen) B54 and Cw1, we administered steroid to him and his physical activity and state of consciousness significantly improved. During the course of treatment, dermal lesion characterisitic of Sweet disease was absent. We diagnosed this case was possible neuro-Sweet disease proposed by Hisanaga in 2005.",,"Nakatani, R.;Naba, I.;Kawasaki, Y.;Moriya, M.;Nakano, M.;Tatsumi, C.",2014,February,,0,
2290,Microbleeds in Alzheimer disease are more related to cerebral amyloid angiopathy than cerebrovascular disease,"Cerebral amyloid angiopathy (CAA) is one of the cardinal pathological features in the vascular components of Alzheimer's disease (AD). CAA itself results in disrupted microvasculature, mainly in the cerebral cortex, eventually leading to a brain cortical or subcortical hemorrhage in a population of elderly people, but clinically overt brain hemorrhages are not so frequent in AD patients. Here we assessed 50 AD patients and 26 controls to detect latent brain hemorrhages with gradient-echo T(2)*-weighted images, a sensitive magnetic resonance imaging technique to detect hemosiderin components in the brain. Microbleeds, demarcated as low-intensity spots in T(2)*-weighted images, were detected in 16.7% of AD patients without cerebrovascular disease (CVD) and in 12.5% of those with CVD, while no microbleeding was detected in the control subjects. No significant difference was observed between the microbleed-positive group and the microbleed-negative counterpart in their clinical background, such as hypertension, the use of antiplatelet drugs and smoking. In addition, white matter high intensities in the T(2)-weighted image were significantly more confluent in the microbleed-positive AD group than its negative counterpart. In conclusion, our evaluation of AD brains revealed that latent microbleeds in AD patients are more frequent than in normal controls. Microbleeds not being related to common hemorrhagic risk factors, but being significantly related to white matter pathologies suggested that microbleeds in AD may be associated with CAA, but not with hypertension or CVD.",Aged;Alzheimer Disease/ pathology/psychology;Brain/pathology;Cerebral Amyloid Angiopathy/ pathology/psychology;Cerebral Hemorrhage/ pathology/psychology;Cerebrovascular Disorders/ pathology/psychology;Female;Hemosiderin/metabolism;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Retrospective Studies,"Nakata-Kudo, Y.;Mizuno, T.;Yamada, K.;Shiga, K.;Yoshikawa, K.;Mori, S.;Nishimura, T.;Nakajima, K.;Nakagawa, M.",2006,,10.1159/000092958,0,
2291,Imaging of Sturge-Weber syndrome: cranial CT and MR findings,"Sturge-Weber syndrome (SWS) is a phakomatosis characterized by vascular nevus flammeus, leptomeningeal venous angiomatosis, seizures, dementia, hemiplegia, hemianopsia, and glaucoma. Various imaging findings (gyriform calcification, atrophy of the ipsilateral hemisphere, leptomeningeal enhancement, ipsilateral choroid plexus enlargement, thickened calvarium, enlargement of paranasal sinuses and mastoid air cells, enlargement of deep veins, and white matter change adjacent to leptomeningeal enhancement) are seen in SWS. We examined the efficacy of CT and MR imaging in making the diagnosis in 14 patients. All patients underwent CT and MRI, and 11 of 14 patients underwent contrast-enhanced MRI. The most specific finding was leptomeningeal enhancement. Gyriform calcification, atrophy of the ipsilateral hemisphere, and ipsilateral chroid plexus enlargement were seen at high frequencies. Thickened calvarium was more frequent in adult patients. Enlargement of paranasal sinuses and mastoid air cells, enlargement of deep veins, and white matter change adjacent to leptomeningeal enhancement were seen in some (3-5) patients. A combination of findings of plain CT and MRI (including postcontrast MRI and MR venography) are useful for diagnosing SWS.","Adolescent;Adult;Child;Child, Preschool;Diagnosis, Differential;Female;Humans;Image Enhancement;Infant;Magnetic Resonance Imaging;Male;Middle Aged;Sturge-Weber Syndrome/ diagnosis;Tomography, X-Ray Computed","Nakata, Y.;Yagishita, A.;Tsuchiya, K.",2004,May,,0,
2292,Diffusion abnormality in posterior cingulate fiber tracts in Alzheimer's disease: tract-specific analysis,"PURPOSE: The aim of this study was to determine diffusion abnormalities in the posterior cingulate fiber tracts (PCFTs) in patients with Alzheimer's disease (AD) by diffusion tensor tractography (DTT). MATERIALS AND METHODS: We studied 23 AD patients and 18 age-matched normal controls who underwent magnetic resonance imaging using diffusion tensor imaging (DTI). DTT of PCFTs was generated from DTI. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in co-registered voxels along with DTT of PCFTs. Student's t-test was used to compare results between the AD patients and normal controls. RESULTS: The MD in PCFTs was significantly higher in AD patients than in normal controls (P = 0.019). The FA in PCFTs was significantly lower in AD patients than in normal controls (P = 0.007). CONCLUSION: The abnormal MD increase and FA decrease, which is considered to indicate a net loss of barriers that restrict water molecular motion and tissue anisotropy of white matter, is consistent with neuropathological data that demonstrate partial loss of myelin, axons, and oligodendrial cells in white matter of AD brains. Our results suggest that MD and FA reflect progression of AD-related histopathological changes in the PCFTs and may represent a useful biological index for monitoring AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ metabolism;Anisotropy;Axons/metabolism/pathology;Case-Control Studies;Diffusion;Diffusion Magnetic Resonance Imaging;Female;Gyrus Cinguli/ metabolism/ pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/metabolism/pathology;Oligodendroglia/metabolism/pathology;Pyramidal Tracts/metabolism/pathology;Severity of Illness Index","Nakata, Y.;Sato, N.;Abe, O.;Shikakura, S.;Arima, K.;Furuta, N.;Uno, M.;Hirai, S.;Masutani, Y.;Ohtomo, K.;Aoki, S.",2008,Oct,10.1007/s11604-008-0258-3,0,
2293,CADASIL with NOTCH3 S180C presenting anticipation of onset age and hallucinations,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to strokes and vascular dementia. The average age of onset for stroke is 45 years with a range of about 30 to 70 years. We describe a Japanese CADASIL family showing S180C in the exon 4 of NOTCH3, presenting an anticipation of the onset age for stroke. MRI demonstrated a similar extent of white matter involvement in younger and older individuals, supporting the presence of anticipation. In addition, hallucinations in 71% of affected patients, and delusions in 57% were also described. Our findings in this family suggest that a specific NOTCH3 mutation was related to unique clinical features, although such correlations have seldom been encountered in CADASIL. © 2005 Elsevier B.V. All rights reserved.",Notch3 receptor;adult;article;CADASIL;clinical article;clinical feature;clinical trial;controlled clinical trial;controlled study;correlation analysis;delusion;exon;family;female;gene mutation;genetic susceptibility;hallucination;human;male;nuclear magnetic resonance imaging;onset age;priority journal;recurrent disease;cerebrovascular accident;white matter,"Nakamura, T.;Watanabe, H.;Hirayama, M.;Inukai, A.;Kabasawa, H.;Matsubara, M.;Mitake, S.;Nakamura, M.;Ando, Y.;Uchino, M.;Sobue, G.",2005,,,0,
2294,Neurotransmitters in dementia,"Changes in the activity of neurotransmitters in dementia were studied by measuring the activities of each of choline acetyltransferase (CAT), dopamine-beta-hydroxylase (DBH) and hydroxylase cofactor (tetrahydrobiopterine; BPH4), and the concentrations of homovanillic acid (HVA) and vasopressin. CAT activity was low in the cerebral cortex of patients with senile dementia of Alzheimer's type (SDAT). The CAT activity was high in the nucleus basalis, which correlated well with the CAT activity in the cerebral cortex, Brodmann areas 22 and 17. DBH activity was lower in the cerebrospinal fluid (CSF) of SDAT and multi-infarct dementia (MID) patients than in that of control subjects. No age-related change was observed in control subjects. Serum DBH activity was decreased in patients with SDAT but not in patients with MID. DBH activity was especially low in the serum of SDAT patients with a low dementia rating score and/or severe brain atrophy shown on computed tomography (CT) scan. Serum DBH activity was also decreased in older normal subjects (greater than or equal to 80 years). The concentration of HVA in the CSF of control subjects decreased with the advance of age, but the decrease in HVA concentration was more pronounced in the CSF of SDAT patients, which would reflect the lowered dopaminergic activity in SDAT. BPH4 activity was also decreased in the CSF of SDAT patients. Arginine-vasopressin was widely demonstrated in the cerebral cortex of control subjects but could not be detected in many areas of the cerebral cortices of demented patients. These results suggest that a deficit of dopamine, noradrenaline or vasopressin as well as acetylcholine may occur in the brain of SDAT patients. The evidence presented points toward areas for consideration in the search for methods of therapy or prevention of SDAT.",Adult;Aged;Alzheimer Disease/*metabolism;Arginine Vasopressin/analysis;Biopterin/analogs & derivatives/cerebrospinal fluid;Central Nervous System/*metabolism;Cerebral Cortex/enzymology;Choline O-Acetyltransferase/metabolism;Dementia/*metabolism;Dopamine beta-Hydroxylase/metabolism;Homovanillic Acid/cerebrospinal fluid;Humans;Middle Aged;Neurotransmitter Agents/*metabolism;Reference Values;Substantia Innominata/enzymology,"Nakamura, S.;Koshimura, K.;Kato, T.;Yamao, S.;Iijima, S.;Nagata, H.;Miyata, S.;Fujiyoshi, K.;Okamoto, K.;Suga, H.;et al.",1984,,,0,
2295,Familial spastic paraplegia with mental impairment and thin corpus callosum,"We described four patients in two families of unique familial spastic paraplegia (FSP) which was thought to be possibly autosomal recessive inheritance. All four patients had quite similar manifestations. Gait disturbance started at their second decade, then spastic paraparesis and mental deterioration progressed slowly. Cerebellar ataxia and sensory loss in the distal parts of four extremities were also slightly presented. In all patients, cranial MRI revealed marked thin corpus callosum with mild changes in the region of periventricular white matter and in the gray matter. Biopsied sural nerves of all patients showed chronic axonal degeneration with mild decrease of both large and small myelinated fibers. Electron microscopic study demonstrated crystalline-like inclusion bodies in the cytoplasm of Schwann cells in all patients. Despite extensive investigation for metabolic disorder, we could not find any abnormality. However an etiology have not established at the time presented, the combination of these clinical features suggested that the disorder could represent a specific clinical entity.",adult;article;case report;computer assisted tomography;familial disease;female;human;human tissue;male;mental deterioration;nuclear magnetic resonance;priority journal;spastic paraplegia,"Nakamura, A.;Izumi, K.;Umehara, F.;Kuriyama, M.;Hokezu, Y.;Nakagawa, M.;Shimmyozu, K.;Izumo, S.;Osame, M.",1995,,,0,
2296,Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder,"We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA level in CD14+ cells ≥10 copies/10(6) cells, and cognitive impairment underwent ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted images, all HIV-infected subjects demonstrated a diffuse ""tram track"" appearance in the perivascular regions of cortical and deep white matter vessels suggesting ferumoxytol uptake in monocytes/ macrophages. This finding was not present in an HIV-seronegative control. While ferumoxytol may have potential as an imaging biomarker for monocyte/macrophage accumulation in patients with HAND, future study is needed. © 2013 Journal of NeuroVirology, Inc.",,"Nakamoto, B. K.;Shikuma, C. M.;Ogata-Arakaki, D.;Umaki, T.;Neuwelt, E. A.;Shiramizu, B. T.;Chow, D. C.;Parikh, N. I.;Kallianpur, K. J.;Hamilton, B. E.",2013,December,,0,
2297,A case of symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"We here report a 42-year-old woman diagnosed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by age, family history, neurological findings, and neuro imagings. Magnetic resonance imaging well demonstrated the multiple lesions in the cerebrum including the brain stem, which was characteristic findings in CADASIL.",,"Nakamizo, A.;Koga, H.;Uyama, E.;Yamabe, K.",2000,Sep,,0,
2298,Involvement of lipoprotein(a) phenotypes in the etiology of cerebral white matter lesion seen in the elderly with geriatric syndrome,"Lipoprotein(a) [Lp(a)], an apolipoprotein(a) combined with apoB100 protein and low-density lipoprotein (LDL) cholesterol, has a variety of phenotypes, mainly due to the number of kringle 4 type 2 within the apolipoprotein(a), and kringle 4 type 2 is extremely similar to plasminogen. Lp(a) is well-known as a risk factor for atherosclerosis, however, the association between Lp(a) phenotypes and the etiology of cerebral white matter lesion, so-called leukoaraiosis seen commonly in the elderly, remains unclear. We therefore conducted a study in 113 elderly patients with geriatric syndrome by assessing MR images and determining the Lp(a) phenotypes. They were divided into 4 groups according to the Fazekas scale for grading leukoaraiosis, and we compared the distribution of Lp(a) phenotypes and background factors in each group. Factors related to severe leuko-araiosis were also studied by multivariate analysis. There were no significant differences in age or gender among groups. Alzheimer disease and cardioembolic stroke were frequently seen in groups without leukoaraiosis or with mild leukoaraiosis, whereas the frequencies of vascular risks, previous history of stroke and vascular dementia were high in group with severe leukoaraiosis. Multivariate analysis showed strong association of S4 homozygote of the Lp(a) phenotype to severe leukoaraiosis, indicating the S4 homozygote as an independent factor for severe leukoaraiosis as well as hypertension, a high level of Lp(a) of 40 mg/dl or more. Among all patients, a high Lp(a) level and S4 homozygote, showing a low level of Lp(a), were seen in 20.4%, respectively. This contradictory finding that high levels of Lp(a) and S4 homozygote were both associated with severe leukoaraiosis indicated the possibility of different mechanisms for developing white matter lesions; a high level of Lp(a) (LDL cholesterol and apoB100 protein rich) promotes atherosclerosis of major arteries such as the carotid artery, while S4 homozygote [low level of Lp(a), which has many kringle 4 type 2] could inhibit fibrinolytic activity with hypercoagulation mediated by competition with plasminogen. Therefore, this suggests that, for elderly individuals with the S4 homozygote, we should pay attention to microcirculatory disturbances in the brain due to fibrinolytic inhibition and hypercoagulation, and formulate aggressive treatment strategies to prevent the development of white matter lesions.",,"Nakai, T.;Koyama, S. I.;Kanetaka, H.;Iwamoto, T.;Arai, H.",2009,April,,0,
2299,Treatment of dural arteriovenous fistula presenting as typical symptoms of hydrocephalus caused by venous congestion: Case report,"A 76-year-old woman presented with a dural arteriovenous fistula (DAVF) manifesting as typical symptoms of normal pressure hydrocephalus such as progressive dementia, gait disturbances, and urinary incontinence. The cerebrospinal fluid pressure during lumbar puncture was 120 mm H(2)O. Computed tomography and magnetic resonance imaging showed ventricular dilation and diffuse white matter changes, which were consistent with the symptoms of hydrocephalus. Cerebral angiography revealed a DAVF in the transverse-sigmoid sinuses with severe cortical venous reflux into the superior sagittal sinus. Transarterial embolization of the feeding arteries reduced the venous flow from the cortical veins into the superior sagittal sinus. Her symptoms improved with reduction in ventricle size. However, she suffered recurrence of the same symptoms several months later. Computed tomography and magnetic resonance imaging demonstrated ventricular dilation associated with hydrocephalus. Angiography revealed a fistulous channel in the left transverse-sigmoid junction. Transvenous embolization was performed resulting in complete obliteration of the fistula. Magnetic resonance image findings such as ventricular dilation and diffuse white matter disappeared and the symptoms of hydrocephalus improved. Although DAVFs often present as venous hypertensive encephalopathy, this case presented with ventricular dilation and diffuse white matter changes, which are the typical neurological signs of normalpressure hydrocephalus. Venous hypertension associated with the DAVF in the transverse-sigmoid sinuses may have been caused by normal pressure hydrocephalus.",,"Nakahara, Y.;Ogata, A.;Takase, Y.;Maeda, K.;Okamoto, H.;Matsushima, T.;Sakata, S.",2011,2011,,0,
2300,Relationship between Silent Brain Infarction and Amount of Daily Coffee Consumption in Middle Age,"BACKGROUND: In aging societies such as that of Japan, it is important to characterize lifestyle-related factors that minimize the occurrence of silent brain infarction (SBI) among the middle aged population for preventing vascular dementia in older age. Little is known about the relationship between amount of coffee consumption and SBI. METHODS: To assess the association between the amount of coffee consumption and SBI in middle age, we statistically analyzed magnetic resonance imaging findings and data from questionnaires of consecutive 242 healthy Japanese individuals whose ages were less than 65 years and who participated in a medical brain-screening program at Teikyo University Chiba Medical Center from June 2008 to June 2009. RESULTS: In comparison with noncoffee drinkers (reference group), coffee drinkers who took 3-4 cups/day and 5 or more cups/day had a statistically lower incidence of SBI (.22, .07-.64, .004 and .43, .19-.99, .043, respectively). Upward logistic regression analysis indicated that SBI was influenced by 3 factors: coffee intake of 3 or more cups/day (.43, .22~.84, .014), history of hypertension (4.2, 2.0~8.8, .0001), and unemployment (2.1, 1.0~4.4, .037). As for consecutive 62 participants whose ages were 65 years or older in the same period, logistic regression analysis did not indicate that drinking coffee affected SBI incidence. CONCLUSIONS: Our report demonstrated that SBI was observed less frequently in middle aged Japanese who consumed 3 cups or more of coffee per day. To avoid senile dementia and/or symptomatic infarction in older age, the middle aged individuals might have to drink more than 3 cups of coffee every day.",0 (Coffee);Academic Medical Centers;Adult;Age Factors;Asymptomatic Diseases;Brain Infarction/diagnostic imaging/ epidemiology/prevention & control;Chi-Square Distribution;Coffee;Female;Humans;Incidence;Japan/epidemiology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Odds Ratio;Protective Factors;Risk Assessment;Risk Factors;Surveys and Questionnaires,"Nakaguchi, H.;Matsuno, A.;Okubo, T.;Hoya, K.",2016,Jul,,0,2301
2301,Relationship between Silent Brain Infarction and Amount of Daily Coffee Consumption in Middle Age,"BACKGROUND: In aging societies such as that of Japan, it is important to characterize lifestyle-related factors that minimize the occurrence of silent brain infarction (SBI) among the middle aged population for preventing vascular dementia in older age. Little is known about the relationship between amount of coffee consumption and SBI. METHODS: To assess the association between the amount of coffee consumption and SBI in middle age, we statistically analyzed magnetic resonance imaging findings and data from questionnaires of consecutive 242 healthy Japanese individuals whose ages were less than 65 years and who participated in a medical brain-screening program at Teikyo University Chiba Medical Center from June 2008 to June 2009. RESULTS: In comparison with noncoffee drinkers (reference group), coffee drinkers who took 3-4 cups/day and 5 or more cups/day had a statistically lower incidence of SBI (.22, .07-.64, .004 and .43, .19-.99, .043, respectively). Upward logistic regression analysis indicated that SBI was influenced by 3 factors: coffee intake of 3 or more cups/day (.43, .22~.84, .014), history of hypertension (4.2, 2.0~8.8, .0001), and unemployment (2.1, 1.0~4.4, .037). As for consecutive 62 participants whose ages were 65 years or older in the same period, logistic regression analysis did not indicate that drinking coffee affected SBI incidence. CONCLUSIONS: Our report demonstrated that SBI was observed less frequently in middle aged Japanese who consumed 3 cups or more of coffee per day. To avoid senile dementia and/or symptomatic infarction in older age, the middle aged individuals might have to drink more than 3 cups of coffee every day.",,"Nakaguchi, H.;Matsuno, A.;Okubo, T.;Hoya, K.",2016,Apr 7,10.1016/j.jstrokecerebrovasdis.2016.01.020,0,
2302,Decreased white matter integrity before the onset of delusions in patients with Alzheimer's disease: Diffusion tensor imaging,"Background: The pathology of delusions in patients with Alzheimer's disease (AD) associated with white matter (WM) abnormalities is poorly understood. In addition, whether the abnormalities in WM integrity that underlie the delusions develop before the onset of the delusions remains unclear. In this study, we used a diffusion tensor imaging approach to examine the existence of baseline abnormalities in WM integrity in AD patients who developed delusions and AD patients who did not develop delusions. Methods: Using the Neuropsychiatric Inventory, we identified patients with AD who exhibit delusions during a 1-year period. All the patients underwent a magnetic resonance imaging (MRI) examination at baseline. We conducted fractional anisotropy using tract-based spatial statistics software and compared the results of AD patients who developed delusions with those who did not develop delusions. Results: Compared with the AD patients who did not develop delusions (n = 15), the AD patients who developed delusions (n = 10) exhibited two relatively large clusters and one minimal cluster of significantly lower fractional anisotropy results. The first cluster was located in the left parieto-occipital region and included several fibers: the left inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the posterior corona radiate, and the forceps major of the corpus callosum. The second cluster was located on the body of the corpus callosum. A third minimal cluster was located on the superior temporal gyrus white matter. Conclusion: Abnormalities in WM integrity involving several fibers may be crucial to the development of delusions in AD patients. © 2013 Nakaaki et al, publisher and licensee Dove Medical Press Ltd.",,"Nakaaki, S.;Sato, J.;Torii, K.;Oka, M.;Negi, A.;Nakamae, T.;Narumoto, J.;Miyata, J.;Furukawa, T. A.;Mimura, M.",2012,21,,0,
2303,Reduction in white matter before and after the development of delusions of theft in a patient with Alzheimer disease,,donepezil;risperidone;aged;Alzheimer disease;brain atrophy;brain size;case report;corpus callosum;delusion;female;human;letter;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;priority journal;white matter,"Nakaaki, S.;Sato, J.;Torii, K.;Kawaguchi, T.;Kawaguchi, A.;Narumoto, J.;Mimura, M.",2013,,,0,
2304,Dementia and capsular genu ischemia in patients with severe bacterial meningitis,"Infarction in the genu of the internal capsule causes dementia that is characterized by abulia, lethargy and memory loss without obvious motor palsy (capsular genu syndrome). We found infarction or decreased cerebral blood flow in the genu of the internal capsule in 6 of 13 patients with severe bacterial meningitis. Four of these six patients developed post-meningitis dementia, characterized by abulia, lethargy, and memory loss. Of 24 patients with viral meningitis, none developed capsular genu ischemia or post-meningitis dementia. In patients with severe bacterial meningitis, capsular genu ischemia may play some role in the development of post-meningitis dementia. In patients with viral meningitis, absence of such ischemia may explain, at least in a part, the rarity of post-meningitis dementia.","Adult;Aged;Brain/pathology/radiography/radionuclide imaging;Brain Infarction/complications/pathology/radionuclide imaging;Brain Ischemia/*complications/pathology/radionuclide imaging;Cerebrovascular Circulation;Dementia/*etiology/pathology/radionuclide imaging;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Meningitis, Bacterial/*complications/pathology/radionuclide imaging;Meningitis, Viral/complications/pathology/radionuclide imaging;Middle Aged;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Naito, M.;Johkura, K.;Momoo, T.;Nomiya, T.;Kudo, Y.;Kuroiwa, Y.",2010,Apr,10.1007/s10072-009-0168-x,0,
2305,Diffusion tensor imaging (DTI) in dementia patients with frontal lobe symptoms,BACKGROUND: Diffusion tensor imaging (DTI) is a recent MRI technique demonstrating white matter tracts in the brain. Dementia is a neurodegenerative disease and this method has been used to demonstrate the loss of axonal fibers and myelin and decrease of fiber density in this condition. PURPOSE: To study a possible correlation between frontal lobe symptoms in patients with dementia and reduced fractional anisotropy (FA) in white matter/fascicles in the frontal lobes. MATERIAL AND METHODS: The study included 23 patients with dementia and frontal lobe symptoms and 20 controls (10 Alzheimer patients without frontal lobe symptoms and 10 normal controls). Clinical tests and MRI with DTI were performed. FA in subcortical white matter of both the frontal lobes was analyzed and correlated with clinical frontal score tests. RESULTS: We found a significant correlation between frontal score results and reduction in FA in the frontal lobes. The FA in the study group was significantly lower than the FA in the control group. CONCLUSION: The present study reveals that there is a probable correlation between the extent of frontal lobe symptoms and FA in fascicles/white matter tissue in the frontal lobes.,"Aged;Aged, 80 and over;Anisotropy;Dementia/ diagnosis/pathology;Diffusion Tensor Imaging;Female;Frontal Lobe/ pathology;Humans;Male","Naik, M.;Lundervold, A.;Nygaard, H.;Geitung, J. T.",2010,Jul,,0,2306
2306,Diffusion tensor imaging (DTI) in dementia patients with frontal lobe symptoms,BACKGROUND: Diffusion tensor imaging (DTI) is a recent MRI technique demonstrating white matter tracts in the brain. Dementia is a neurodegenerative disease and this method has been used to demonstrate the loss of axonal fibers and myelin and decrease of fiber density in this condition. PURPOSE: To study a possible correlation between frontal lobe symptoms in patients with dementia and reduced fractional anisotropy (FA) in white matter/fascicles in the frontal lobes. MATERIAL AND METHODS: The study included 23 patients with dementia and frontal lobe symptoms and 20 controls (10 Alzheimer patients without frontal lobe symptoms and 10 normal controls). Clinical tests and MRI with DTI were performed. FA in subcortical white matter of both the frontal lobes was analyzed and correlated with clinical frontal score tests. RESULTS: We found a significant correlation between frontal score results and reduction in FA in the frontal lobes. The,,"Naik, M.;Lundervold, A.;Nygaard, H.;Geitung, J. T.",1987,Jul,,0,
2307,Diffusion tensor imaging in early Alzheimer's disease,"Our aim was to investigate the extent of white matter tissue damage in patients with early Alzheimer disease (AD) using diffusion tensor magnetic resonance imaging (DTI). Although AD pathology mainly affects cortical grey matter, previous magnetic resonance imaging (MRI) studies showed that changes also exist in the white matter (WM). However, the nature of",,"Naggara, O.;Oppenheim, C.;Rieu, D.;Raoux, N.;Rodrigo, S.;Dalla Barba, G.;Meder, J. F.",2006,30,,0,
2308,CT brain findings in clinical dementia investigation--underestimation of mixed dementia,"Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.","Aged;Alzheimer Disease/blood/diagnosis/radiography;Atrophy/radiography;Basal Ganglia/pathology/radiography;Cerebral Infarction/pathology/radiography;Dementia/blood/diagnosis/*radiography;Female;Fluorescence Polarization Immunoassay;Homocysteine/blood;Humans;Male;Temporal Lobe/pathology/radiography;Tomography, X-Ray Computed","Nagga, K.;Radberg, C.;Marcusson, J.",2004,,10.1159/000077737,0,
2309,Increased levels of hyaluronic acid in cerebrospinal fluid in patients with vascular dementia,"Hyaluronic acid (HA) has been shown to affect angiogenesis and the function of the blood-brain barrier, and a crucial role for HA in atherosclerosis has been described. We have recently demonstrated changes in the levels of HA in cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) with documented vascular alterations. To further investigate if the level of HA in CSF can be used as a clinical diagnostic biomarker to identify vascular pathology in dementia, we analyzed the levels of HA in the CSF of patients with vascular dementia (VaD) (n = 46), AD (n = 45), and controls without dementia (n = 26). In line with our previous data, we found significantly increased levels of HA in CSF from patients with VaD compared with controls, whereas the levels of HA in patients with AD were found to be unaltered compared with controls and patients with VaD. We also detected increased levels of HA in individuals with vascular changes determined as significant white matter changes or previous infarction on cranial computed tomography or magnetic resonance imaging, compared with individuals without these findings. Furthermore, we found a significant positive correlation between the levels of HA and the CSF/serum albumin ratio, an indicator of blood-brain barrier integrity, in patients with VaD and AD, supporting the role of HA in vascular changes in the brain. Our results indicate a potential diagnostic value for the detection of vascular brain changes in dementia using CSF levels of HA, but emphasize the importance of further development of more sensitive HA assays.","Aged;Albumins/metabolism;Alzheimer Disease/cerebrospinal fluid;Amyloid beta-Peptides/blood;Biomarkers/blood/cerebrospinal fluid;Brain/pathology;Dementia, Vascular/blood/ cerebrospinal fluid/pathology;Female;Humans;Hyaluronic Acid/ cerebrospinal fluid;Male;Middle Aged;Neuropsychological Tests;Peptide Fragments/blood;Phosphorylation;tau Proteins/blood","Nagga, K.;Hansson, O.;van Westen, D.;Minthon, L.;Wennstrom, M.",2014,,10.3233/jad-141200,0,
2310,Idiopathic transdural anastomoses in elderly patients with atherosclerotic ischemic cerebrovascular disease - Two case reports,"Two patients with atherosclerotic ischemic cerebrovascular disease presented with transdural anastomoses. A 74-year-old woman had a cerebral infarct, and a 76-year-old man had dementia. Patients with atherosclerotic ischemic cerebrovascular disease may have developed transdural anastomoses, so care must be taken not to damage these functions during revascularization surgery.",aged;anamnesis;anastomosis;arteriography;article;atherosclerotic ischemic cerebrovascular disease;brain artery;brain infarction;brain ischemia;carotid artery;case report;clinical feature;female;human;magnetic resonance angiography;male;meningeal artery;nuclear magnetic resonance imaging;occlusive cerebrovascular disease;surgical technique,"Nagata, S. I.;Kazekawa, K.;Aikawa, H.;Kanemaru, R.;Tanioka, K.;Kawanishi, A.;Dogomori, H.;Kanai, J.",2007,,,0,
2311,Cerebrovascular lesions in elderly Japanese patients with Alzheimer's disease,"OBJECTIVE: Cerebrovascular lesions (CVLs) are known to play important roles in the pathophysiology underlying Alzheimer's disease (AD), especially in elderly AD cases. The present study was conducted to elucidate the relationship between the CVLs and vascular risk factors (VRFs) in elderly Japanese patients with AD. SUBJECTS AND METHODS: The CVLs such as lacunar infarcts, old microbleeds (OMBs), white matter lesions (WMLs), and occlusive vascular lesions on MRI were analyzed in relation to the risk factors in 120 Japanese patients with probable AD. Their mean age was 75.6 years. The subjects were divided into two age groups: young-old group (YOG) consisting of 55 cases being younger than 75 years and old-old group (OOG) consisting of 65 cases being 75 years or older. RESULTS: In overall analysis, 10 cases (8.3%) showed brain atrophy without CVLs on MRI, 46 cases (38.3%) showed WMLs in addition to the brain atrophy, 61 cases (50.8%) showed lacunar lesions, and 3 cases (2.5%) were diagnosed as having a superficial siderosis. Lacunar infarcts and OMBs were more frequently observed in OOG than in YOG, and were also more frequently observed in those with 2 or more VRFs than those with less than 2 VRFs (p<0.05). The WMLs were more pronounced in OOG, and in those with more VRFs. CONCLUSION: The CVLs including lacunes, WMLs, and OMBs were present more than 90% of elderly Japanese patients with AD. As the severity of CVLs was associated with VRFs and age, VRFs may modify clinical presentation of elderly AD patients.","Age Factors;Aged;Aged, 80 and over;*Aging;Alzheimer Disease/*epidemiology/*pathology;Brain/*pathology/radiography;Cerebrovascular Disorders/*epidemiology;Female;Humans;Japan/epidemiology;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Mental Status Schedule;Nerve Fibers, Myelinated/pathology;Risk Factors","Nagata, K.;Takano, D.;Yamazaki, T.;Maeda, T.;Satoh, Y.;Nakase, T.;Ikeda, Y.",2012,Nov 15,10.1016/j.jns.2012.07.001,0,
2312,Prevalence and clinicoradiological analyses of patients with Alzheimer disease coexisting multiple microbleeds,"BACKGROUND: Pathologic findings of cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD) coexist frequently. Both diseases are associated with beta-amyloid deposition and dementia. We aimed to evaluate frequency and clinicoradiological profile of AD patients with multiple microbleeds (MBs). METHODS: We reviewed clinical records and magnetic resonance imaging (MRI) findings in patients with probable AD diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria from 2009 to 2012. Brain MRI was performed at 1.5-T superconducting system, including T2*-weighted gradient-echo imaging. MBs were defined as rounded, hypointense foci less than or equal to 10 mm in size in the brain parenchyma. MBs topography was divided into the lobar (L) and the deep/infratentorial (D/I) region. Multiple MBs were defined as the number greater than or equal to 8 in the L and the D/I territory, respectively. White matter hyperintensities (WMHs) were assessed using the age-related white matter changes scale. Clinicoradiological findings were examined for 1 year. Prevalence and clinicoradiological profiles were studied in patients with multiple L or D/I MBs. RESULTS: Five hundred fifty patients (238 men and 312 women) participated in the present study. Mean age (standard deviation) was 78.4 (7.7) years, 78.3 (8.1) years in men and 78.6 (7.5) years in women. A total of 132 patients (55 men and 78 women) had at least 1 MB. Prevalence of MB >/= 1 was 24%, 23 in men and 25 in women. The ratio of L and D/I MBs were 1.1, .6 in men and 1.8 in women. Multiple MBs were detected in 93 patients (17%), 38 (16%) men and 55 (17%) in women. L distribution was found in 49 patients (9%), 15 men (6%) and 34 women (11%), and D/I distribution in 44 patients (8%), 23 men (10%) and 21 women (7%). Multiple L MBs was associated with faster progression of dementia, cerebral hemorrhage, and increased number of MBs. Multiple D/I MBs were linked to hypertension and WMH scores. CONCLUSIONS: The present study indicated that the prevalence of multiple MBs was 17% in Japanese AD patients. The clinicoradiological profile suggested severe degree of CAA in patients with multiple L MBs (9%) and hypertension and aged changes in patients with multiple D/I MBs (8%). T2*-weighted imaging is a useful tool for evaluating degree of CAA and hypertensive vascular changes. We should pay more attention to management and care in AD patients with multiple MBs.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ epidemiology/ pathology/radiography;Asian Continental Ancestry Group/ statistics & numerical data;Cerebral Angiography;Female;Humans;Intracranial Hemorrhages/complications/ epidemiology/ pathology/radiography;Japan/epidemiology;Magnetic Resonance Imaging;Male;Microcirculation;Neuropsychological Tests;Prevalence;Risk Factors","Nagasawa, J.;Kiyozaka, T.;Ikeda, K.",2014,Oct,10.1016/j.jstrokecerebrovasdis.2014.05.036,0,
2313,Hypersexuality in nursing care facilities--a descriptive study,"The continuance of sexual expression in the elderly as age advances is well recognized. Sexual disinhibition, however, in a restricted environment such as in nursing care facilities has received scant attention. We wish to describe eight patients residing in nursing care facilities who were seen because of their problematic sexually related behaviors. These behaviors include cuddling, touching of the genitals, sexual remarks propositioning, grabbing and groping, use of obscene language and masturbating without shame. In all instances concern emanated from members of the nursing staff. Other associated behaviors included aggression, agitation, and irritability amongst others. The computed tomography (CT) scan of the brain showed infarction in the frontal lobe (4), parietal lobe (1), and the caudate (1). One had severe Parkinson's Disease and one had severe dementia of the Alzheimer's disease. All ten patients had an organic basis for their symptoms. Sexually inappropriate behaviors remain highly controversial and labeling them as 'diseased' or an 'illness' may have enormous individual, cultural and medico-legal implications. The clinico-anatomical correlation are discussed.",,"Nagaratnam, N.;Gayagay, G., Jr.",2002,Nov-Dec,,0,
2314,Cerebral white matter hyperintensity predicts cardiovascular events in haemodialysis patients,"Aim: Cerebral white matter hyperintensities (WMHs), comprised of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH), have been presumed to be predictors for future stroke, cognitive impairment and dementia in the general population. However, no longitudinal studies have been performed to determine the clinical significance of WMHs in haemodialysis (HD) patients. In the present study, we investigated the influence of WMHs as a predictor of future cardiovascular disease in HD patients. Methods: Cranial magnetic resonance imaging was performed on 179 HD patients with no past history of stroke from April 2006 to October 2009, and the prevalence of WMHs was investigated. The patients were followed prospectively until March 2012 or death or renal transplantation. The influence of WMHs on cardiovascular events was investigated using the Kaplan-Meier method and Cox proportional hazards analysis. Results: The patients with advanced PVH and DSWMH had a significantly higher incidence of cardiovascular morbidity than those without advanced PVH and DSWMH by Kaplan-Meier analysis. By multivariate Cox proportional hazards analysis, the presence of advanced PVH and DSWMH increased the risk of cardiovascular events, independent of other cardiovascular risk factors. In addition, the present study revealed that of the subtypes of WMHs, PVH was a stronger predictor of cardiovascular events compared to DSWMH. Conclusions: The present study indicates that the presence of WMHs is a novel predictor of cardiovascular events in HD patients, and that PVH is more closely associated with incident cardiovascular disease. Summary at a Glance This study conducted in a cohort of Japanese haemodialysis patients with no previous stroke history showed that the presence of white matter hyperintensity on MRI is a novel predictor of cardiovascular events. Furthermore, of the subtypes of white matter hyperintensity, periventricular hyperintensity is more closely associated with incident cardiovascular disease. © 2013 Asian Pacific Society of Nephrology.",,"Naganuma, T.;Takemoto, Y.;Shoji, T.;Shima, H.;Ishimura, E.;Okamura, M.;Nakatani, T.",2013,October,,0,
2315,Factors associated with cerebral white matter hyperintensities in haemodialysis patients,"AIM: Cerebral white matter hyperintensities (WMHs), comprising periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) on magnetic resonance imaging (MRI), have been reported to be markers of ischaemic cerebral small-vessel disease and risk factors for future stroke, cognitive impairment and dementia in the general population. However, there have been only a few reports describing WMHs in haemodialysis (HD) patients and these previous studies have been relatively small population studies with little investigation on prevalence and risk factors according to the regional subtypes of WMHs. METHODS: Cranial MRI was performed on 179 HD patients and 58 healthy control subjects and we investigated the prevalence of WMHs (PVH and/or DSWMH) and the clinical factors associated with the presence of WMHs. RESULTS: The prevalence of WMHs was significantly higher in the HD patients than in the healthy subjects. In the HD patients, multiple logistic regression analysis showed that independent and significant factors associated with the presence of PVH were age, female gender and systolic blood pressure and those associated with the presence of DSWMH were age, female gender, systolic blood pressure and body mass index. CONCLUSIONS: These findings indicated a high prevalence of WMHs in HD patients. Older age, female gender and high blood pressure were strong factors associated with the presence of both PVH and DSWMH. Moreover, excess body weight was a significant factor associated with the presence of DSWMH only, indicating that there may be differences in risk factors according to the subtype of WMHs.","Adult;Age Factors;Aged;Aged, 80 and over;Body Mass Index;Brain/ pathology;Case-Control Studies;Chi-Square Distribution;Cross-Sectional Studies;Female;Humans;Hypertension/epidemiology;Japan/epidemiology;Leukoencephalopathies/diagnosis/ epidemiology/pathology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Odds Ratio;Overweight/diagnosis/epidemiology;Predictive Value of Tests;Prevalence;Renal Dialysis/adverse effects;Renal Insufficiency, Chronic/epidemiology/ therapy;Risk Assessment;Risk Factors;Severity of Illness Index;Sex Factors;Young Adult","Naganuma, T.;Takemoto, Y.;Shoji, T.;Shima, H.;Ishimura, E.;Okamura, M.;Nakatani, T.",2012,Aug,10.1111/j.1440-1797.2012.01596.x,0,
2316,Neuroimaging and neuropathologic findings in AIDS patient with cytomegalovirus infection,"This 21-year-old male with hemophilia A developed cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS). He had a history of numerous blood transfusions. Serum antibody titers became positive for human immunodeficiency virus (HIV), when the patient was 18 years of age. Three years later, he developed CMV retinitis due to his immunosuppression. Ganciclovir (Denosine®, Tanabe Seiyaku Co., Ltd., Osaka, Japan) therapy given for 4 weeks produced a marked improvement in the ocular fundal findings, but the neurologic signs and symptoms, including headache, hypoesthesia, disorientation, and dementia became worse. T2-weighted magnetic resonance imaging (MRI) demonstrated a diffuse high intensity area in the periventricular white matter and small focal or patchy lesions in the hippocampus, basal ganglia, midbrain, medulla oblongata and the nucleus dentatus. The patient died of HIV encephalopathy and CMV infection. Characteristic CMV intranuclear inclusion bodies were observed histologically in most sites of the brain including the hippocampus, white matter, basal ganglia, midbrain, medulla oblongata, nucleus dentatus and the retina. Infiltration by monocyte-macrophage and multinucleated giant cells, which are characteristic of HIV encephalopathy, were observed in the periventricular white matter and the hippocampus. In this patient, the neuroimaging findings were compatible with the neuropathologic observations.",,"Nagamitsu, S.;Okabayashi, S.;Dai, S.;Morimitsu, Y.;Murakami, T.;Matsuishi, T.;Motizuki, M.;Kato, H.",1994,1994,,0,
2317,Decreased computerized tomography numbers in patients with presenile dementia. Detection in patients with otherwise normal scans,"Patients in their 50s who show clinical signs of dementia (possible Alzheimer's disease) often have ocmputerized tomographic (CT) scans that appear normal. This study examined the mean CT number within a 169-pixel sample in white matter in the centrum semiovale slice. Slice sizes ranged from 6,800 to 9,000 pixels; all were without contrast enhancement. The CT numbers were higher for six nondementia cases (CT numbers of 41 and above)than for 14 dementia cases (CT numbers of 40 and below). The non-overlap in mean CT numbers between the two groups was observed independent of the presence or absence of prominent sulci. Similar low CT numbers were observed for seven patients with senile dementia. Differential diagnosis between dementia and depression may be better aided by studying the CT numbers rather than the presence of prominent sulci.","Aged;Brain/*radiography;Cerebrovascular Disorders/radiography;Dementia/diagnosis/*radiography;Depression/diagnosis;Diagnosis, Differential;Humans;Huntington Disease/radiography;Male;Middle Aged;Retrospective Studies;*Tomography, X-Ray Computed","Naeser, M. A.;Gebhardt, C.;Levine, H. L.",1980,Jul,,0,
2318,Six-minute magnetic resonance imaging protocol for evaluation of acute ischemic stroke: Pushing the boundaries,"BACKGROUND AND PURPOSE - : If magnetic resonance imaging (MRI) is to compete with computed tomography for evaluation of patients with acute ischemic stroke, there is a need for further improvements in acquisition speed. METHODS - : Inclusion criteria for this prospective, single institutional study were symptoms of acute ischemic stroke within 24 hours onset, National Institutes of Health Stroke Scale ≥3, and absence of MRI contraindications. A combination of echo-planar imaging (EPI) and a parallel acquisition technique were used on a 3T magnetic resonance (MR) scanner to accelerate the acquisition time. Image analysis was performed independently by 2 neuroradiologists. RESULTS - : A total of 62 patients met inclusion criteria. A repeat MRI scan was performed in 22 patients resulting in a total of 84 MRIs available for analysis. Diagnostic image quality was achieved in 100% of diffusion-weighted imaging, 100% EPI-fluid attenuation inversion recovery imaging, 98% EPI-gradient recalled echo, 90% neck MR angiography and 96% of brain MR angiography, and 94% of dynamic susceptibility contrast perfusion scans with interobserver agreements (k) ranging from 0.64 to 0.84. Fifty-nine patients (95%) had acute infarction. There was good interobserver agreement for EPI-fluid attenuation inversion recovery imaging findings (k=0.78; 95% confidence interval, 0.66-0.87) and for detection of mismatch classification using dynamic susceptibility contrast-Tmax (k=0.92; 95% confidence interval, 0.87-0.94). Thirteen acute intracranial hemorrhages were detected on EPI-gradient recalled echo by both observers. A total of 68 and 72 segmental arterial stenoses were detected on contrast-enhanced MR angiography of the neck and brain with k=0.93, 95% confidence interval, 0.84 to 0.96 and 0.87, 95% confidence interval, 0.80 to 0.90, respectively. CONCLUSIONS - : A 6-minute multimodal MR protocol with good diagnostic quality is feasible for the evaluation of patients with acute ischemic stroke and can result in significant reduction in scan time rivaling that of the multimodal computed tomographic protocol. © 2014 American Heart Association, Inc.",,"Nael, K.;Khan, R.;Choudhary, G.;Meshksar, A.;Villablanca, P.;Tay, J.;Drake, K.;Coull, B. M.;Kidwell, C. S.",2014,July,,0,
2319,Statins and brain integrity in older adults: secondary analysis of the Health ABC study,"INTRODUCTION: We examined whether statins are associated with better cerebral white (WM) and gray matter (GM) indices in community-dwelling elders. METHODS: In 295 older adults, we compared white matter hyperintensities (WMH) on brain magnetic resonance imaging and, total WM fractional anisotropy (FA) and GM mean diffusivity (MD) on diffusion tensor imaging, of Alzheimer's disease (AD) relevant regions in statin-exposed and statin-unexposed participants stratified by Modified Mini-Mental Status Examination (3MS) score. RESULTS: There was no overall effect of statin exposure on cerebral structural indices. The interaction between statin exposure and 3MS was significant for total-WMH and WM FA (both P < .05) but not GM MD. In the lowest 3MS tertile (mean: 86), statin-exposed individuals had lower total-WMH and higher WM FA (P = .005 and P = .044) and FA of tracts linked to clinical AD (P-value range= .005-.04) despite statistical adjustments. These differences were not significant in the two higher 3MS tertiles. DISCUSSION: Statins may benefit WM in older adults vulnerable to dementia.",,"Nadkarni, N. K.;Perera, S.;Hanlon, J. T.;Lopez, O.;Newman, A. B.;Aizenstein, H.;Elam, M.;Harris, T. B.;Kritchevsky, S.;Yaffe, K.;Rosano, C.",2015,Oct,10.1016/j.jalz.2014.11.003,0,
2320,A case of an elderly patient with dementia and gait disturbance associated with influenza,"We report a case of progressive dementia and prolonged gait disturbance correlated with influenza A/H3N2 infection in 91-year-old female patient, admitted because of in ability to take care of herself due to aging and cerebral infarction. At admission, conversation and comprehension were not significantly impaired, and she was able to walk by herself. Flu symptoms such as high grade fever, chills, arthralgia, and cough appeared after a short stay at home. Influenza A/ H3N2 was confirmed serologically. Delirium occurred on the sixth day after influenza onset, persisted for three weeks, followed by recovery. Dementia symptoms such as memory defects and disorientation continued and did not improve. Due to this febrile episode, she was unable to walk unassisted. The results of computed tomography performed before and after the influenza episode were unremarkable for additional cellebro-vascular events during the observed period. Influenza infection may be an important risk factor for reducing the quality of life in the elderly. In geriatric cases, influenza should not be treated as a mere transient illness, but rather one which has important consequences for the elderly population, including the possibility of life threatening complications.",aged;article;case report;dementia;female;gait;human;influenza;Influenza A virus;multiinfarct dementia;quality of life,"Nabeshima, A.;Ikematsu, H.;Yamaga, S.;Nakagawa, M.;Umezaki, T.;Hara, H.;Hayashi, J.;Kashiwagi, S.",1997,,,0,
2321,Cortical superficial siderosis: a marker of vascular amyloid in patients with cognitive impairment,"OBJECTIVE: To investigate the prevalence and associations of cortical superficial siderosis (cSS) utilizing MRI markers of cerebral small vessel disease and amyloid burden assessed through in vivo amyloid imaging in a cognitively impaired population. METHODS: Gradient-recalled echo, T2*-weighted MRIs from 232 patients (Alzheimer disease-related cognitive impairment [ADCI], n = 90; subcortical vascular cognitive impairment [SVCI], n = 142) were reviewed for cSS. All subjects underwent in vivo amyloid imaging using [(11)C] Pittsburgh compound B (PiB)-PET. A multivariate logistic regression model was constructed to evaluate the predictive factors of cSS. A follow-up MRI was performed in 154 (66.4%) of 232 patients. RESULTS: Twelve patients (5.2%) with cSS were equally distributed in ADCI (n = 6) and SVCI (n = 6) groups, but cSS was not present in any of the patients with a negative PiB scan. cSS was associated with markers of cerebral amyloid angiopathy, including higher global PiB retention ratio, APOE epsilon2 allele presence, and a strictly lobar distribution of cerebral microbleeds. Of those patients with baseline cSS, 33% showed progression over time; there were 2 cases of symptomatic intracranial hemorrhage. CONCLUSIONS: cSS occurred in both ADCI and SVCI groups, but not in patients with amyloid-negative SVCI, supporting the hypothesis that cSS reflects an amyloid rather than ischemic etiology. The associations with strictly lobar cerebral microbleeds and APOE epsilon2 suggest that cerebral amyloid angiopathy, with increased vascular fragility related to APOE genotype, contributes to cSS in this population, with a high risk of progression over time and future intracranial hemorrhage.","Aged;Aged, 80 and over;Cerebral Hemorrhage/ diagnosis/epidemiology/psychology;Cerebral Small Vessel Diseases/ diagnosis/epidemiology/psychology;Cognition Disorders/ diagnosis/epidemiology/psychology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Plaque, Amyloid/ diagnosis/epidemiology/psychology;Siderosis/ diagnosis/epidemiology/psychology","Na, H. K.;Park, J. H.;Kim, J. H.;Kim, H. J.;Kim, S. T.;Werring, D. J.;Seo, S. W.;Na, D. L.",2015,Feb 24,10.1212/wnl.0000000000001288,0,
2322,Addictive substances may induce a rapid neurological deterioration in fragile X-associated tremor ataxia syndrome: A report of two cases,"A debilitating late-onset disorder of the premutation in the FMR1 gene is the neurodegenerative disorder fragile X-associated tremor ataxia syndrome (FXTAS). We report two patients with FXTAS who have a history of substance abuse (opiates, alcohol, and cocaine) which may have exacerbated their rapid neurological deterioration with FXTAS. There has been no case report regarding the role of substance abuse in onset, progression, and severity of FXTAS symptoms. However, research has shown that substance abuse can have a negative impact on several neurodegenerative diseases, and we propose that in these cases, substance abuse contributed to a faster progression of FXTAS as well as exacerbated white matter disease.",alcohol;cocaine;codeine;hydrocodone bitartrate plus paracetamol;opiate;adult;aged;airway obstruction;alcohol abuse;article;ataxia;backache;breathing disorder;case report;Caucasian;cocaine dependence;cognitive defect;dysgraphia;dysphagia;falling;female;fragile X associated tremor ataxia syndrome;fragile X syndrome;human;leg disease;leg pain;limb weakness;male;mental deterioration;middle aged;neurologic disease;nuclear magnetic resonance imaging;opiate addiction;pneumonia;tremor,"Muzar, Z.;Adams, P. E.;Schneider, A.;Hagerman, R. J.;Lozano, R.",2014,,,0,
2323,Gray matter contamination in arterial spin labeling white matter perfusion measurements in patients with dementia,"INTRODUCTION: White matter (WM) perfusion measurements with arterial spin labeling can be severely contaminated by gray matter (GM) perfusion signal, especially in the elderly. The current study investigates the spatial extent of GM contamination by comparing perfusion signal measured in the WM with signal measured outside the brain. MATERIAL AND METHODS: Four minute 3T pseudo-continuous arterial spin labeling scans were performed in 41 elderly subjects with cognitive impairment. Outward and inward geodesic distance maps were created, based on dilations and erosions of GM and WM masks. For all outward and inward geodesic distances, the mean CBF was calculated and compared. RESULTS: GM contamination was mainly found in the first 3 subcortical WM voxels and had only minor influence on the deep WM signal (distances 4 to 7 voxels). Perfusion signal in the WM was significantly higher than perfusion signal outside the brain, indicating the presence of WM signal. CONCLUSION: These findings indicate that WM perfusion signal can be measured unaffected by GM contamination in elderly patients with cognitive impairment. GM contamination can be avoided by the erosion of WM masks, removing subcortical WM voxels from the analysis. These results should be taken into account when exploring the use of WM perfusion as micro-vascular biomarker.","Aged;Aged, 80 and over;Brain Mapping;Cerebrovascular Circulation/*physiology;Dementia/*diagnosis;Female;Gray Matter/*blood supply/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mental Status Schedule;Pulsatile Flow/physiology;*Spin Labels;White Matter/*blood supply/pathology;ASL, arterial spin labeling;Arterial spin labeling;CBF, cerebral blood flow;CSF, cerebrospinal fluid;Dementia;GM, gray matter;Gray matter contamination;PSF, point spread function;PV, partial volume;Partial volume;SNR, signal-to-noise ratio;WM, white matter;White matter perfusion","Mutsaerts, H. J.;Richard, E.;Heijtel, D. F.;van Osch, M. J.;Majoie, C. B.;Nederveen, A. J.",2014,,10.1016/j.nicl.2013.11.003,0,
2324,Unusual cause of stroke: CADASIL with novel mutation in Czech patient,"Cerebral antosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary, small vessel disease caused by mutations in the NOTCH3 gene encoding a transmembrane receptor of vascular smooth muscle cells. Clinical symptoms include recurrent strokes, migraine, and dementia in mid-adulthood. We report a patient with stroke who turned out to have CADASIL. The diagnosis was suspected because of the family history, absent vascular risk factors and magnetic resonance imaging findings with typical involvement of anterior temporal lobes, periventricular regions and external capsule. The diagnosis of the first verified Czech patient with CADASIL was confirmed by electron microscopical and immunohistochemical findings in the skin biopsy specimen and by genetic analysis, which identified a novel NOTCH3 mutation. The mutation is located in an EGF-like repeat in exon 6 and it results in change of glycine 296 residue for a cysteine residue, which is typical for CADASIL. We hope that better awareness of this rare and underdiagnosed disease will help to identify more patients with CADASIL in Czech Republic.",,"Musil, L.;Bartoš, A.;Matěj, R.;Elleder, M.;Hřebíěk, M.",2006,2006,,0,
2325,Functional impact of white matter hyperintensities in cognitively normal elderly subjects,"Objective: To investigate the impact white matter hyperintensities (WMH) detected on magnetic resonance imaging have on motor dysfunction and cognitive impairment in elderly subjects without dementia. Design: Cross-sectional study. Setting: Population-based study on the incidence and prevalence of cognitive impairment in Olmsted County, Minnesota. Participants: A total of 148 elderly subjects (65 men) without dementia ranging in age from 73 to 91 years. Main Outcome Measures: We measured the percentage of the total white matter volume classified as WMH in a priori-defined brain regions (ie, frontal, temporal, parietal, occipital, periventricular, or subcortical). Motor impairment was evaluated qualitatively using the Unified Parkinson's Disease Rating Scale summary measures of motor skills and quantitatively using a digitized portable walkway system. Four cognitive domains were evaluated using z scores of memory, language, executive function, and visuospatial reasoning. Results: A higher WMH proportion in all regions except the occipital lobewasassociated with lower executive function z score (P value <.01). A higher WMH proportion in all regions, butmoststrongly for the parietal lobe, correlated with higher Unified Parkinson's Disease Rating Scale gait, posture,andpostural stabilitysum(P value <.01).Ahigher WMH proportion, whether periventricular, subcortical, or lobar, correlated with reduced velocity (P value <.001). Conclusions: We conclude that executive function is the primary cognitive domain affected by WMH burden. The data suggest that WMH in the parietal lobe are chiefly responsible for reduced balance and postural support compared with the other 3 lobes and may alter integration of sensory information via parietal lobe dysfunction in the aging brain. Parietal white matter changes were not the pre-dominant correlate with motor speed, lending evidence to a global involvement of neural networks in gait velocity. ©2010 American Medical Association. All rights reserved.",,"Murray, M. E.;Senjem, M. L.;Petersen, R. C.;Hollman, J. H.;Preboske, G. M.;Weigand, S. D.;Knopman, D. S.;Ferman, T. J.;Dickson, D. W.;Jack Jr, C. R.",2010,November,,0,
2326,Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum,"Thal amyloid phase, which describes the pattern of progressive amyloid-beta plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing - Alzheimer's Association neuropathologic assessment guidelines. Amyloid biomarkers (positron emission tomography and cerebrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia published by the National Institute of Ageing - Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem (11)C-Pittsburgh compound B imaging; using the large autopsy cohort to broaden our perspective of (11)C-Pittsburgh compound B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morbidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. (11)C-Pittsburgh compound B studies from Mayo Clinic Rochester were available for 35 participants scanned within 2 years of death. Cortical (11)C-Pittsburgh compound B values were calculated as a standard uptake value ratio normalized to cerebellum grey/white matter. In the high likelihood Alzheimer's disease brain bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-epsilon4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, but not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, but not Braak tangle stage or cerebral amyloid angiopathy predicted (11)C-Pittsburgh compound B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition between Thal amyloid phases 1 to 2 seemed to correspond to (11)C-Pittsburgh compound B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer's disease cases who were older and were APOE-epsilon4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer's disease patients, the pre-mortem clinical status was driven by Braak tangle stage. Thal amyloid phase correlated best with (11)C-Pittsburgh compound B values, but not Braak tangle stage or cerebral amyloid angiopathy. The (11)C-Pittsburgh compound B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1-2.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology;Amyloid/metabolism;Amyloid beta-Peptides/ metabolism;Aniline Compounds;Female;Humans;Male;Middle Aged;Plaque, Amyloid/ pathology;Positron-Emission Tomography/methods;Thiazoles","Murray, M. E.;Lowe, V. J.;Graff-Radford, N. R.;Liesinger, A. M.;Cannon, A.;Przybelski, S. A.;Rawal, B.;Parisi, J. E.;Petersen, R. C.;Kantarci, K.;Ross, O. A.;Duara, R.;Knopman, D. S.;Jack, C. R., Jr.;Dickson, D. W.",2015,May,10.1093/brain/awv050,0,
2327,Early life socioeconomic circumstance and late life brain hyperintensities - A population based cohort study,"Context: There have been many reports confirming the association between lower childhood socioeconomic circumstance and cardiovascular disease but evidence for links with cerebrovascular disease is contradictory. Hyperintensities on brain magnetic resonance imaging are associated with vascular risk factors, cognitive decline, dementia and death. However, the relationship between childhood socioeconomic circumstance and these lesions is unclear. Objective: To test the hypothesis that childhood socioeconomic circumstance is associated with late life hyperintensity burden and that neither adult socioeconomic circumstance nor change in socioeconomic circumstance during life influence this effect. Design: Cohort study Setting: Community Participants: 227 community dwelling members of the 1936 Aberdeen Birth Cohort aged 68 years, who were free from dementia. Main Outcome Measures: Relationship between early life socioeconomic circumstance (paternal occupation) and abundance of late life brain hyperintensities. Results: We find significant negative correlations between childhood socioeconomic circumstance and white matter hyperintensities (ρ = -0.18, P<0.01), and periventricular hyperintensities (ρ = -0.15, P<0.05), between educational attainment and white matter hyperintensities (ρ = -0.15, P<0.05) and periventricular hyperintensities (ρ = -0.17, P<0.05), and between childhood intelligence and periventricular hyperintensities (ρ = -0.14, P<0.05). The relationship is strongest for childhood socioeconomic circumstance and regional white matter hyperintensities, where there is a step change in increased burden from paternal occupation grades equivalent to a shift from ""white collar"" to ""blue collar"" paternal occupation. Significant correlations were also found between hypertension and hyperintensity burden in all brain regions (ρ = 0.15-0.24, P<0.05). In models that include hypertension, the magnitude of the effect of childhood socioeconomic circumstance is similar to and independent from that of hypertension. Conclusions: Childhood socioeconomic circumstance predicts the burden of brain white matter hyperintensities aged 68 years. The mechanism underlying this effect is unknown, but may act through fetal and/or early life programming of cerebrovascular disease. Future work to understand this vulnerability will inform strategies to reduce dementia and stroke. © 2014 Murray et al.",adulthood;aged;article;blue collar worker;brain hyperintensity;brain region;brain ventricle;childhood;cohort analysis;community living;disease association;educational status;employment status;father;human;hypertension;intelligence;nervous system parameters;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;population research;poverty;socioeconomics;structural equation modeling;white collar worker;white matter;1.5T NVi system,"Murray, A. D.;McNeil, C. J.;Salarirad, S.;Whalley, L. J.;Staff, R. T.",2014,,,0,2328
2328,Early life socioeconomic circumstance and late life brain hyperintensities--a population based cohort study,"CONTEXT: There have been many reports confirming the association between lower childhood socioeconomic circumstance and cardiovascular disease but evidence for links with cerebrovascular disease is contradictory. Hyperintensities on brain magnetic resonance imaging are associated with vascular risk factors, cognitive decline, dementia and death. However, the relationship between childhood socioeconomic circumstance and these lesions is unclear. OBJECTIVE: To test the hypothesis that childhood socioeconomic circumstance is associated with late life hyperintensity burden and that neither adult socioeconomic circumstance nor change in socioeconomic circumstance during life influence this effect. DESIGN: Cohort study. SETTING: Community. PARTICIPANTS: 227 community dwelling members of the 1936 Aberdeen Birth Cohort aged 68 years, who were free from dementia. MAIN OUTCOME MEASURES: Relationship between early life socioeconomic circumstance (paternal occupation) and abundance of late life brain hyperintensities. RESULTS: We find significant negative correlations between childhood socioeconomic circumstance and white matter hyperintensities (rho = -0.18, P<0.01), and periventricular hyperintensities (rho = -0.15, P<0.05), between educational attainment and white matter hyperintensities (rho = -0.15, P<0.05) and periventricular hyperintensities (rho = -0.17, P<0.05), and between childhood intelligence and periventricular hyperintensities (rho = -0.14, P<0.05). The relationship is strongest for childhood socioeconomic circumstance and regional white matter hyperintensities, where there is a step change in increased burden from paternal occupation grades equivalent to a shift from ""white collar"" to ""blue collar"" paternal occupation. Significant correlations were also found between hypertension and hyperintensity burden in all brain regions (rho = 0.15-0.24, P<0.05). In models that include hypertension, the magnitude of the effect of childhood socioeconomic circumstance is similar to and independent from that of hypertension. CONCLUSIONS: Childhood socioeconomic circumstance predicts the burden of brain white matter hyperintensities aged 68 years. The mechanism underlying this effect is unknown, but may act through fetal and/or early life programming of cerebrovascular disease. Future work to understand this vulnerability will inform strategies to reduce dementia and stroke.",Aged;Analysis of Variance;Cerebrovascular Disorders/ epidemiology/ pathology;Cohort Studies;Fathers;Humans;Magnetic Resonance Imaging;Occupations;Scotland/epidemiology;Socioeconomic Factors,"Murray, A. D.;McNeil, C. J.;Salarirad, S.;Whalley, L. J.;Staff, R. T.",2014,,10.1371/journal.pone.0088969,0,
2329,Widespread cerebral haemodynamics disturbances occur early in amyotrophic lateral sclerosis,"We wished to longitudinally assess early changes in cerebral perfusion (CP) and its relationship to cognitive impairment (CI) in ALS. Fourteen ALS patients at time of diagnosis and 11 spousal controls, both without CI, were longitudinally assessed to determine a relationship between CP and incidence of CI in early stage disease. Neuropsychological testing and CP measurements were performed in both ALS and control groups at the initial assessment (T0) and two time-periods post initial assessment, T1 and T2, taken on average 6.1 and 17.0 months after initial assessment (T0), respectively. CT perfusion was used to measure cerebral blood flow, blood volume, and mean transit time (MTT) for all cortical lobes, and subcortical grey and white matter. Two of 14 ALS patients progressed to CI. No differences in CP measurements existed at T0 or T1 between the ALS and control groups. At T2, widespread cortical differences in MTT were present between the two groups. The ALS group had significantly increased MTT in all cortical regions, as well as the thalamus, compared with the control group. Our findings suggest early widespread changes in CP occur outside the motor area in the absence of CI in ALS. © 2012 Informa Healthcare.",adult;aged;amyotrophic lateral sclerosis;article;brain blood volume;brain cortex;brain perfusion;clinical article;cognitive defect;controlled study;female;gray matter;human;longitudinal study;male;neuroimaging;neuropsychological test;priority journal;temporal lobe;thalamus;white matter,"Murphy, M. J.;Grace, G. M.;Tartaglia, M. C.;Orange, J. B.;Chen, X.;Rowe, A.;Findlater, K.;Kozak, R. I.;Freedman, M.;Lee, T. Y.;Strong, M. J.",2012,,,0,
2330,Conspicuity and evolution of lesions in Creutzfeldt-Jakob disease at diffusion-weighted imaging,"BACKGROUND AND PURPOSE: Diffusion-weighted imaging can disclose distinct hyperintense lesions in Creutzfeldt-Jakob disease (CJD). However, these findings and chronologic changes of CJD at diffusion-weighted imaging have not been fully investigated. Our purpose was to assess the diagnostic value of diffusion-weighted imaging in depicting CJD-related lesions and in tracking the evolution of these lesions. We also compared the sensitivity of diffusion-weighted imaging in depicting CJD-related lesions to that of fluid-attenuated inversion recovery (FLAIR) imaging. METHODS: We reviewed findings in 13 patients with a diagnosis of CJD who underwent MR imaging, including diffusion-weighted imaging. Nine patients were initially examined within 4 months of onset of symptoms (early stage), and eight were examined 4 months or later (late stage). We evaluated four items: 1) distribution of lesions at diffusion-weighted imaging, 2) conspicuity of lesions at diffusion-weighted imaging and FLAIR imaging, 3) chronologic changes in lesions at diffusion-weighted imaging, and 4) chronologic changes in lesions revealed by apparent diffusion coefficient (ADC) maps. RESULTS: Patients had striatal lesions or cerebral cortical lesions or both. The thalamus was involved in only one patient, and the globus pallidus was spared in all patients. The sensitivity of diffusion-weighted imaging in depicting lesions was superior or at least equal to that of FLAIR imaging. Hyperintense lesions at diffusion-weighted imaging changed in extent and intensity over time. Unlike infarction, lesional ADC decreased for 2 weeks or longer. CONCLUSION: The progressively hyperintense changes in the striata and cerebral cortices at diffusion-weighted imaging are considered characteristic of CJD. Diffusion-weighted imaging may be useful for the early diagnosis of CJD.","Aged;Aged, 80 and over;Brain/blood supply/radiography;Creutzfeldt-Jakob Syndrome/ diagnosis;Disease Progression;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Middle Aged;Sensitivity and Specificity;Severity of Illness Index;Time Factors","Murata, T.;Shiga, Y.;Higano, S.;Takahashi, S.;Mugikura, S.",2002,Aug,,0,
2331,Familial Binswanger-type encephalopathy with Sneddon syndrome,"We reported a family with early onset cerebrovascular disease. Patient 1 (a 36-year old man) demonstrated a combination of livedo reticularis and cerebral infarction as previously described as Sheddon syndrome. He also showed transient focal neurologic symptoms and mild dementia. Patient 2 (an elder sister of Patient 1) was suffering from migraine. Their father and paternal uncle died of cerebral infarction, which had developed in their thirties or forties. Patients 1 and 2 showed MRI findings compatible with encephalopathy with Binswanger-type. Contrary to the previous reports on Binswanger-type encephalopathy, both of these patients demonstrated decreased levels of fibrinogen as well as those of factor V, together with negative antiphospholipid antibody. Thus, juvenile onset, autosomal dominant inheritance, the diversity of clinical findings and the coagulopathy in this family were characteristic features. The level of thrombin-antithrombin III complex (TAT) was markedly increased in Patient 1. Treatment with antithrombin (argatroban 20mg i.v. everyday for 28days) not truly reduced the level of TAT but also improved the livedo reticularis and neurological findings. Although gene analysis has not been performed yet on this family, this condition is similar to cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), which involve juvenile cerebral infarction and dementia as well as migraine.",antithrombin III;argatroban;thrombin;adult;aged;article;Binswanger encephalopathy;blood clotting disorder;brain infection;clinical article;clinical feature;family study;female;human;male;migraine;onset age;Sneddon syndrome,"Murase, N.;Kanda, M.;Satoi, H.;Kaji, R.;Akiguchi, I.",1996,,,0,
2332,"Various pathophysiological states of acute symptomatic seizures immediately after ischemic stroke, namely “onset seizures,” shown by complementary use of peri-ictal magnetic resonance imaging and electroencephalography","Background: “Onset seizures” are acute symptomatic seizures occurring within 24 h after the onset of ischemic stroke, and their pathophysiological states are unknown. Electroencephalography is commonly used to diagnose epileptic activities; however, it is limited for use with acute stroke. Magnetic resonance imaging, including diffusion-weighted imaging and perfusion imaging with arterial spin labeling, are applied mainly in an emergency. Ictal hyperperfusion on arterial spin labeling and cortical hyperintensity of cytotoxic edema on diffusion-weighted imaging, peri-ictally, can be obtained from an epileptically activated cortex. Aim: We aimed to show pathophysiological states of onset seizures by complementary use of peri-ictal magnetic resonance imaging and electroencephalography. Methods: Four patients diagnosed as onset seizures underwent an initial magnetic resonance imaging and subsequent electroencephalography. Results: In case 1, having persistent non-convulsive status epilepticus after control of onset seizures, ictal magnetic resonance imaging and electroencephalography findings clearly showed the topographical relationship between the acute atherothrombotic infarction and the peri-infarction activated cortex. In case 2, with multiple embolic strokes in the bifrontal lobes, prolonged arterial spin labeling hyper signals were observed in the perirolandic area of the right leg; cortical hyperintensity on diffusion-weighted imaging and paroxysmal activities on electroencephalography were not shown. In cases 3 and 4, postictal hypoperfusion was shown in the large extent involving the multiple embolic infarctions. Because the epileptic cortex was located in the convexity, electroencephalography clearly showed inter-ictal paroxysms in case 3, and localized slow wave in case 4. Conclusion: The present study shows that the complementary use of peri-ictal arterial spin labeling/diffusion-weighted imaging and electroencephalography potentially offers the ability to document the various pathophysiological states of onset seizure.",acetylsalicylic acid;anticonvulsive agent;carbamazepine;diazepam;fosphenytoin sodium;levetiracetam;norphenazone;phenobarbital;warfarin;aged;arterial spin labeling;article;brain infarction;brain ischemia;brain scintiscanning;case report;clinical article;confusion;deep vein thrombosis;dementia;diffusion weighted imaging;disorientation;electroencephalography;epileptic state;female;follow up;frontal lobe;hemiparesis;hospitalization;human;low drug dose;male;nuclear magnetic resonance imaging;onset seizure;perfusion;priority journal;Rankin scale;retrospective study;symptomatic epilepsy;thrombosis;tonic clonic seizure;transesophageal echocardiography;very elderly,"Murao, K.;Morioka, T.;Shimogawa, T.;Furuta, Y.;Haga, S.;Sakata, A.;Arihiro, S.;Arakawa, S.",2017,,10.1111/ncn3.12160,0,
2333,Kernel eigenspace template matching for detection of lacunar infarcts on MR images,"Detection of lacunar infarcts is important because their presence indicates an increased risk of severe cerebral infarction and dementia. However, accurate identification of lacunar infarcts is often difficult for radiologists. Our previous computer-aided detection (CAD) scheme achieved a sensitivity of 96.8% with 0.76 false positives (FPs) per slice. However, further reduction of FPs remained an issue for the clinical application. The purpose of this study is to improve our CAD scheme by using kernel eigenspace template matching. First, we selected the regions of interest (ROIs) around the candidate regions detected in our previous method. A kernel eigenspace was then made by using kernel principal component analysis of the training data set. A test ROI was projected onto the same kernel eigenspace as the training data set. The cross-correlation coefficients between the test ROI and all the training ROIs were calculated on the kernel eigenspace. By comparing the two maxima of coefficients with a lacunar ROI and an FP ROI, the test ROI was classified. By using the proposed method, the quantity of the templates became 1.9% of that in template matching on the real space and 31. 9% of FPs could be eliminated while keeping the same sensitivity; nevertheless 30.3% of FPs were eliminated when we employed the eigenspace template matching under the same condition. Therefore, kernel eigenspace template matching could improve FP rate without a significant reduction in the true positive rate.","Diagnosis, Computer-Assisted;False Positive Reactions;Humans;Magnetic Resonance Imaging/ methods;Sensitivity and Specificity;Stroke, Lacunar/ diagnosis","Murakawa, S.;Tanigawa, A.;Uchiyama, Y.;Muramatsu, C.;Hara, T.;Fujita, H.",2015,Feb,10.6009/jjrt.2015_JSRT_71.2.85,0,
2334,Parental longevity is associated with cognition and brain ageing in middle-aged offspring,"BACKGROUND: offspring of long-lived individuals have lower risk for dementia. We examined the relation between parental longevity and cognition and subclinical markers of brain ageing in community-dwelling adult offspring. METHODS: offspring participants with both parents in the Framingham Heart Study, aged >/=55 years and dementia-free underwent baseline and repeat neuropsychological (NP) testing and brain magnetic resonance imaging (MRI). Parental longevity was defined as having at least one parent survive to age >/=85 years. To test the association between parental longevity and measures of cognition and brain volumes, we used multivariable linear and logistic regression adjusting for age, sex, education and time to NP testing or brain MRI. RESULTS: of 728 offspring (mean age 66 years, 54% women), 407 (56%) had >/=1 parent achieve longevity. In cross-sectional analysis, parental longevity was associated with better scores on attention (beta 0.21 +/- 0.08, P = 0.006) and a lower odds of extensive white matter hyperintensity on brain MRI (odds ratio 0.59, 95% CI: 0.38, 0.92, P = 0.019). The association with white matter hyperintensity was no longer significant in models adjusted for cardiovascular risk factors and disease. In longitudinal analysis (6.7 +/- 1.7 years later), offspring with parental longevity had slower decline in attention (0.18 +/- 0.08, P = 0.038), executive function (beta 0.19 +/- 0.09, P = 0.031) and visual memory (beta -0.18 +/- 0.08, P = 0.023), and less increase in temporal horn volume (beta -0.25 +/- 0.09, P = 0.005). The associations persisted in fully adjusted models. CONCLUSION: parental longevity is associated with better brain ageing in middle-aged offspring.","Adult Children/ psychology;Aged, 80 and over;Aging/physiology/psychology;Brain/pathology/physiology/physiopathology;Cognition;Dementia/diagnosis/epidemiology;Executive Function;Female;Humans;Longevity;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Organ Size;Parents;Prognosis;Risk Assessment;Statistics as Topic","Murabito, J. M.;Beiser, A. S.;Decarli, C.;Seshadri, S.;Wolf, P. A.;Au, R.",2014,May,10.1093/ageing/aft175,0,
2335,"Dentatorubropallidoluysian atrophy in a Spanish family: A clinical, radiological, pathological, and genetic study","The object was to describe the clinical, radiological, pathological, and genetic findings in a Spanish family with dentatorubropallidoluysian atrophy (DRPLA). This is an inherited neurodegenerative disease, well recognised in Japan, but with few cases reported from Europe and America and no cases published from Spain. The clinical misdiagnosis of Huntington's disease is not infrequent. Pedigree analysis and clinical data of a family were collected. A genetic study was performed in two patients. Pathological information was obtained from the necropsy of one patient. Results - Pedigree analysis showed an autosomal dominant pattern of inheritance. Age at onset varied from 5 to 55 years. Ataxia and chorea were present in most of the members. Some of these had a long course disease with late dementia. Four patients had seizures and early mental impairment. In one patient, cranial MRI showed cortical, brain stem and cerebellar atrophy, and white matter changes. In another patient, necropsy showed atrophy of the globus pallidus and lipofuscin deposits in dentate and pallidal neuronal cells. Genetic study showed an abnormal CAG triplet expansion in the B37 gene on chromosome 12. As in other cases previously reported, Spanish cases of DRPLA show intrafamilial phenotypic heterogeneity. Clinical and MRI data could differentiate DRPLA from Huntingon's disease but definitive diagnosis requires molecular studies. Pathological studies are still necessary to correlate DRPLA brain involvement with the clinical and molecular findings.",lipofuscin;adolescent;adult;article;ataxia;autopsy;brain atrophy;brain stem;cerebellum atrophy;chorea;chromosome 12;clinical article;degenerative disease;dementia;dentate nucleus;dentatorubropallidoluysian atrophy;differential diagnosis;female;gene mutation;globus pallidus;human;Huntington chorea;Japan;mental deficiency;neuropathology;nuclear magnetic resonance imaging;onset age;pedigree analysis;priority journal;seizure;Spain;white matter,"Muñoz, E.;Milà, M.;Sánchez, A.;Latorre, P.;Ariza, A.;Codina, M.;Ballesta, F.;Tolosa, E.",1999,,,0,
2336,Severe cerebral white matter involvement in a case of dentatorubropallidoluysian atrophy studied at autopsy,"Background: The pathophysiology of white matter involvement in dentatorubropallidoluysian atrophy (DRPLA) is controversial. Moreover, the clinical repercussions and evolution of these lesions have not been well documented. Objective: To describe a case of DRPLA with severe cerebellar white matter involvement. Design: Case report. Patient: A 62-year-old woman with DRPLA. Results: When the genetic diagnosis was made, the patient manifested severe ataxia, slight dysarthria, and subcortical cognitive impairment. Cranial magnetic resonance imaging showed atrophy of the cerebellum and brainstem and moderate high-intensity signal alterations in the periventricular cerebral white matter in T2-weighted sequences. In the following 5 years, she developed uncontrolled head movements associated with severe bruxism and tetraparesis, and became deeply demented. New magnetic resonance imaging showed severe diffuse cerebral white matter alterations in T2 sequences with only slight progression of brainstem and cerebellar atrophy. After her death at 67 years of age, the autopsy study showed diffuse myelin pallor, axonal preservation, and reactive astrogliosis in the cerebral white matter, with only mild atherosclerotic changes, and moderate neuronal loss in the cerebellum and brainstem. Conclusions: Leukoencephalopathy could be a prominent finding in some patients with DRPLA, explaining, at least in part, their clinical evolution. In our case, the disproportion between the severity of white matter damage and vascular changes does not support a cardinal role for ischemic mechanisms in leukoencephalopathy.",,"Muñoz, E.;Campdelacreu, J.;Ferrer, I.;Rey, M. J.;Cardozo, A.;Gómez, B.;Tolosa, E.",2004,June,,0,
2337,Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease,"OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/psychology;Cerebral Cortex/pathology;Cerebrovascular Disorders/*pathology/psychology;Cognition Disorders/*pathology/psychology;Female;Follow-Up Studies;Forecasting;Hippocampus/pathology;Humans;Longitudinal Studies;*Magnetic Resonance Imaging/statistics & numerical data;Male;Middle Aged;Neuropsychological Tests/statistics & numerical data;Regression Analysis","Mungas, D.;Reed, B. R.;Jagust, W. J.;DeCarli, C.;Mack, W. J.;Kramer, J. H.;Weiner, M. W.;Schuff, N.;Chui, H. C.",2002,Sep 24,,0,
2338,Age and education effects on relationships of cognitive test scores with brain structure in demographically diverse older persons,"This study examined how age and education influence the relationship between neuropsychological test scores and brain structure in demographically diverse older adults spanning the range from normal cognition to dementia. A sample of 351 African Americans, 410 Hispanics, and 458 Whites underwent neuropsychological testing. Volumetric magnetic resonance imaging (MRI) measures of total brain, white matter hyperintensity, and hippocampus were available for 79 African Americans, 102 Hispanics, and 134 Whites. The authors used latent variable modeling to examine effects of age, education, and brain volumes on test scores and determine how much variance brain volumes explained in unadjusted and age- and education-adjusted scores. Age adjustment resulted in weaker relationships of test scores with MRI variables; adjustment for ethnicity yielded stronger relationships. Education adjustment increased relationships with MRI variables in the combined sample and Hispanics, made no difference in Whites, but decreased some associations in African Americans. Results suggest that demographic adjustment is beneficial when demographic variables are strongly related to test scores independent of measures of brain structure, but adjustment has negative consequences when effects of demographic characteristics are mediated by brain structure.","African Americans/psychology;Age Factors;Aged;Atrophy;Brain/ pathology;Cognition Disorders/ diagnosis/ethnology;Cross-Cultural Comparison;Dementia/ diagnosis/ethnology;Educational Status;European Continental Ancestry Group/psychology;Female;Hippocampus/pathology;Hispanic Americans/psychology;Humans;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests/ statistics & numerical data;Organ Size/physiology;Psychometrics","Mungas, D.;Reed, B. R.;Farias, S. T.;Decarli, C.",2009,Mar,10.1037/a0013421,0,
2339,MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease,"Background: Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. Objective: To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. Methods: Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. Results: Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. Conclusions: Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.",aged;Alzheimer disease;article;brain atrophy;brain injury;brain ischemia;brain ventricle;cerebrovascular disease;cognition;cognitive defect;controlled study;dementia;female;human;major clinical study;male;multiple regression;neuropsychological test;nuclear magnetic resonance imaging;priority journal;white matter,"Mungas, D.;Jagust, W. J.;Reed, B. R.;Kramer, J. H.;Weiner, M. W.;Schuff, N.;Norman, D.;Mack, W. J.;Willis, L.;Chui, H. C.",2001,,,0,
2340,Longitudinal volumetric MRI change and rate of cognitive decline,"OBJECTIVE: To examine how baseline and change of volumetric MRI relate to cognitive decline in older individuals. BACKGROUND: Memory is associated with hippocampal integrity, whereas executive function has been linked to impaired frontal lobe function. Previous studies have shown that hippocampal and cortical atrophy are more strongly related to cognition than are measures of subcortical cerebrovascular disease (CVD). The authors hypothesized that memory (MEM) decline would be related to change in hippocampal volume (HC), whereas decline in executive function (EXEC) would be related to change of cortical gray matter volume (CGM) and measures of subcortical CVD. METHODS: Subjects from a multicenter study (n = 103) included cognitively normal, mildly impaired, and demented cases with and without subcortical lacunes. All had longitudinal cognitive evaluation (mean = 4.8 years) and two or more MRI scans at least one year apart (mean = 3.4 years). MRI measures included HC, CGM, total lacune volume (LAC), and white matter hyperintensity volume (WMH). Random effects modeling of longitudinal data assessed effects of MRI baseline and MRI change on baseline and change of psychometrically matched measures of MEM and EXEC. RESULTS: Change in MEM was related to HC baseline and HC change. Change in EXEC was related to baseline CGM and to change in CGM, HC, and LAC. Results were unchanged when demented cases were excluded. WMH was not associated with change in MEM or EXEC independent of HC, CGM, and LAC. CONCLUSION: Hippocampal volume was the primary determinant of memory decline, whereas executive function (EXEC) decline was related to multiple brain components. Results support a hypothesis that MEM decline is strongly influenced by Alzheimer disease (AD), whereas EXEC decline may be complexly determined by cerebrovascular disease and AD.","Aged;Aged, 80 and over;Aging/*pathology;Alzheimer Disease/diagnosis/physiopathology/psychology;Atrophy/*diagnosis/etiology/physiopathology;Brain/*pathology/physiopathology;Cerebral Cortex/pathology/physiopathology;Cognition Disorders/*diagnosis/physiopathology/psychology;Data Collection;Dementia/diagnosis/physiopathology;Dementia, Vascular/diagnosis/physiopathology/psychology;Disease Progression;Female;Hippocampus/pathology/physiopathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory Disorders/*diagnosis/physiopathology/psychology;Middle Aged;Neuropsychological Tests;Predictive Value of Tests","Mungas, D.;Harvey, D.;Reed, B. R.;Jagust, W. J.;DeCarli, C.;Beckett, L.;Mack, W. J.;Kramer, J. H.;Weiner, M. W.;Schuff, N.;Chui, H. C.",2005,Aug 23,10.1212/01.wnl.0000172913.88973.0d,0,
2341,"In a case of Alzheimer's disease, aggressiveness disappeared after an infarction in the anterior thalamic nucleus",,atypical antipsychotic agent;neuroleptic agent;aged;Alzheimer disease;article;basal ganglion;brain infarction;case report;diffusion weighted imaging;female;human;nuclear magnetic resonance imaging;priority journal;thalamus anterior nucleus,"Muneoka, K.;Igawa, M.;Kida, J.;Mikami, T.;Ishihara, I.;Uchida, J.;Uchida, S.;Hirasawa, H.",2008,,,0,
2342,Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia,"Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.",Diffusion tensor imaging;Emotion detection;Personality;Primary progressive aphasia;Social cognition,"Multani, N.;Galantucci, S.;Wilson, S. M.;Shany-Ur, T.;Poorzand, P.;Growdon, M. E.;Jang, J. Y.;Kramer, J. H.;Miller, B. L.;Rankin, K. P.;Gorno-Tempini, M. L.;Tartaglia, M. C.",2017,,,0,
2343,DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age,"DJ-1 is a protein with anti-oxidative stress and anti-apoptotic properties that is abundantly expressed in reactive CNS astrocytes in chronic neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Pick's disease. Genetic mutations which eliminate DJ-1 expression in humans are sufficient to produce an early-onset form of familial PD, PARK7, suggesting that DJ-1 is a critical component of the neuroprotective arsenal of the brain. Previous studies in parkinsonism/dementia brain tissues have revealed that reactive astrocytes within and surrounding incidentally identified infarcts were often robustly immunoreactive for DJ-1, especially if the infarcts showed histological features consistent with older age. Given this, we sought to evaluate astrocytic DJ-1 expression in human stroke more extensively, and with a particular emphasis on determining whether immunohistochemical DJ-1 expression in astrocytes correlates with histological infarct age. The studies presented here show that DJ-1 is abundantly expressed in reactive infarct region astrocytes in both gray and white matter, that subacute and chronic infarct region astrocytes are much more robustly DJ-1+ than are acute infarct and non-infarct region astrocytes, and that DJ-1 staining intensity in astrocytes generally correlates with that of the reactive astrocyte marker GFAP. Confocal imaging of DJ-1 and GFAP dual-labelled human brain sections were used to confirm the localization to and expression of DJ-1 in astrocytes. Neuronal DJ-1 staining was minimal under all infarct and non-infarct conditions. Our data support the conclusion that the major cellular DJ-1 response to stroke in the human brain is astrocytic, and that there is a temporal correlation between DJ-1 expression in these cells and advanced infarct age.","Adult;Aged;Aged, 80 and over;Analysis of Variance;Astrocytes/ metabolism/pathology;Brain/ metabolism/pathology;Brain Infarction/ metabolism/pathology;Female;Fluorescent Antibody Technique;Glial Fibrillary Acidic Protein/metabolism;Humans;Immunohistochemistry;Intracellular Signaling Peptides and Proteins/ metabolism;Male;Microscopy, Confocal;Middle Aged;Neurons/metabolism;Oncogene Proteins/ metabolism;Stroke;Time Factors;Young Adult","Mullett, S. J.;Hamilton, R. L.;Hinkle, D. A.",2009,Apr,10.1111/j.1440-1789.2008.00955.x,0,
2344,Bilateral paramedian thalamic infarct. A case report with NMR and gamma emission tomography study,"A 41-year-old woman presented with a history of sudden onset of a dementia with frontal signs and antero-retrograde amnesia. CT showed a bilateral paramedian thalamic infarct which was confirmed by MRI. The study of regional cerebral blood flow showed a decrease in both frontal regions. Results of imaging suggested lesions of the ventro-oral, latero-polar and intralaminar nuclei as well as of the mamillo-thalamic tract. The dorso-median nucleus appeared to be relatively spared.",,"Muller Ph, J.;Destee, A.;Steinling, M.;Pruvo, J. P.;Warot, P.",1989,1989,,0,
2345,Joint effect of mid- and late-life blood pressure on the brain: the AGES-Reykjavik study,"OBJECTIVE: We hypothesized that in participants with a history of hypertension, lower late-life blood pressure (BP) will be associated with more brain pathology. METHODS: Participants are 4,057 older men and women without dementia with midlife (mean age 50 +/- 6 years) and late-life (mean age 76 +/- 5 years) vascular screening, cognitive function, and brain structures on MRI ascertained as part of the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. RESULTS: The association of late-life BP to brain measures depended on midlife hypertension history. Higher late-life systolic and diastolic BP (DBP) was associated with an increased risk of white matter lesions and cerebral microbleeds, and this was most pronounced in participants without a history of midlife hypertension. In contrast, in participants with a history of midlife hypertension, lower late-life DBP was associated with smaller total brain and gray matter volumes. This finding was reflected back in cognitive performance; in participants with midlife hypertension, lower DBP was associated with lower memory scores. CONCLUSION: In this large population-based cohort, late-life BP differentially affects brain pathology and cognitive performance, depending on the history of midlife hypertension. Our study suggests history of hypertension is critical to understand how late-life BP affects brain structure and function.","Adult;Aged;Aged, 80 and over;Aging/pathology/physiology;Analysis of Variance;Blood Pressure/*physiology;Brain/*pathology;Cognition/physiology;Disease Susceptibility;Female;Humans;Hypertension/epidemiology/*pathology/physiopathology;Iceland/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies","Muller, M.;Sigurdsson, S.;Kjartansson, O.;Aspelund, T.;Lopez, O. L.;Jonnson, P. V.;Harris, T. B.;van Buchem, M.;Gudnason, V.;Launer, L. J.",2014,Jun 17,10.1212/wnl.0000000000000517,0,
2346,Motor network structure and function are associated with motor performance in Huntington’s disease,"In Huntington’s disease, the relationship of brain structure, brain function and clinical measures remains incompletely understood. We asked how sensory-motor network brain structure and neural activity relate to each other and to motor performance. Thirty-four early stage HD and 32 age- and sex-matched healthy control participants underwent structural magnetic resonance imaging (MRI), diffusion tensor, and intrinsic functional connectivity MRI. Diffusivity patterns were assessed in the cortico-spinal tract and the thalamus–somatosensory cortex tract. For the motor network connectivity analyses the dominant M1 motor cortex region and for the basal ganglia-thalamic network the thalamus were used as seeds. Region to region structural and functional connectivity was examined between thalamus and somatosensory cortex. Fractional anisotropy (FA) was higher in HD than controls in the basal ganglia, and lower in the external and internal capsule, in the thalamus, and in subcortical white matter. Between-group axial and radial diffusivity differences were more prominent than differences in FA, and correlated with motor performance. Within the motor network, the insula was less connected in HD than in controls, with the degree of connection correlating with motor scores. The basal ganglia-thalamic network’s connectivity differed in the insula and basal ganglia. Tract specific white matter diffusivity and functional connectivity were not correlated. In HD sensory-motor white matter organization and functional connectivity in a motor network were independently associated with motor performance. The lack of tract-specific association of structure and function suggests that functional adaptation to structural loss differs between participants.",,"Müller, H. P.;Gorges, M.;Grön, G.;Kassubek, J.;Landwehrmeyer, G. B.;Süßmuth, S. D.;Wolf, R. C.;Orth, M.",2016,1,,0,
2347,Stability of white matter changes related to huntington's disease in the presence of imaging noise: A DTI study,"Movement artifacts and other sources of noise are a matter of concern particularly in the neuroimaging research of movement disorders such as Huntington's disease (HD). Using diffusion weighted imaging (DWI) and fractional anisotropy (FA) as a compound marker of white matter integrity, we investigated the effect of movement on HD specific changes in magnetic resonance imaging (MRI) data and how post hoc compensation for it affects the MRI results. To this end, we studied by 3T MRI: 18 early affected, 22 premanifest gene-positive subjects, 23 healthy controls (50 slices of 2.3 mm thickness per volume, 64 diffusion-weighted directions (b = 1000 s/mm2), 8 minimal diffusion-weighting (b = 100 s/mm2)); and by 1.5 T imaging: 29 premanifest HD, 30 controls (40 axial slices of 2.3 mm thickness per volume, 61 diffusion-weighted directions (b = 1000 s/mm2), minimal diffusion-weighting (b = 100 s/mm2)). An outlier based method was developed to identify movement and other sources of noise by comparing the index DWI direction against a weighted average computed from all other directions of the same subject. No significant differences were observed when separately comparing each group of patients with and without removal of DWI volumes that contained artifacts. In line with previous DWI-based studies, decreased",,"Müller, H. P.;Glauche, V.;Novak, M.;Nguyen-Thanh, T.;Unrath, A.;Lahiri Swales, N.;Read, J.;Say, M. J.;Tabrizi, S. J.;Kassubek, J.;Kloppel, S.",2011,,,0,
2348,Association between vitamin B6 and white matter hyperintensities in patients with Alzheimer's disease not mediated by homocysteine metabolism [2],,cyanocobalamin;folic acid;homocysteine;methionine;pyridoxine;adult;aged;Alzheimer disease;amino acid metabolism;blood sampling;controlled study;disease association;fluorescence polarization immunoassay;human;letter;logistic regression analysis;major clinical study;methylation;Mini Mental State Examination;nuclear magnetic resonance imaging;risk factor;vitamin blood level;white matter,"Mulder, C.;Van Der Flier, W. M.;Veerhuis, R.;Bouwman, F.;Jakobs, C.;Verhoeven, N. M.;Barkhof, F.;Scheltens, P.;Blankenstein, M. A.",2007,,,0,
2349,Association between vitamin B6 and white matter hyperintensities in patients with Alzheimer's disease not mediated by homocysteine metabolism,,"Aged;Aged, 80 and over;Alzheimer Disease/*blood/*pathology;Brain/*pathology;Homocysteine/*metabolism;Humans;Magnetic Resonance Imaging;Middle Aged;Vitamin B 6/*blood","Mulder, C.;van der Flier, W. M.;Veerhuis, R.;Bouwman, F.;Jakobs, C.;Verhoeven, N. M.;Barkhof, F.;Scheltens, P.;Blankenstein, M. A.",2007,Jun,10.1111/j.1532-5415.2007.01174.x,0,
2350,Low vitamin B6 levels are associated with white matter lesions in Alzheimer's disease [1],,pyridoxal 5 phosphate;pyridoxine;semicarbazide;adult;aged;Alzheimer disease;blood analysis;brain atrophy;brain disease;controlled study;female;fluorescence analysis;high performance liquid chromatography;human;letter;male;Mini Mental State Examination;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;pyridoxine deficiency;vascular lesion;vitamin blood level;white matter,"Mulder, C.;Scheltens, P.;Barkhof, F.;Gundy, C.;Verstraeten, R. A.;De Leeuw, F. E.",2005,,,0,
2351,Prevalence and types of cognitive impairment among patients with stroke attending a Referral Hospital in Uganda,"Background Cognitive impairment is associated with short and long term adverse outcomes in stroke patients that may impair functional recovery during their rehabilitative process. Aims This study determined the prevalence, grades and demographic factors associated with cognitive impairment among patients with stroke attending Mulago National Referral Hospital in Uganda, a teaching hospital for Makerere University College of Health Sciences. Methods This was a cross-sectional descriptive study conducted from Mulago National Referral Hospital between June 2006 and March 2007. Eighty five patients with stroke confirmed by brain computed tomography scan, consenting either by themselves or by their guardians, were consecutively recruited from the Medical wards, Neurology clinic and the Physiotherapy department. A standardized questionnaire was interviewer administered, to obtain demographic and clinical data, and the Mini-Mental State Examination instrument was used to screen and grade cognitive impairment. Results Of the 85 patients evaluated, 70 (82.4%) had infarct and 15 (17.6%) hemorrhagic stroke. Fifty-four (63%, 95% confidence interval (CI): 53 - 73) had cognitive impairment; of which 23 (27%) and 14 (16%) had mild and moderate cognitive impairment respectively accounting for 43% of the cognitively impaired but with no dementia, and 17 (20%) had severe cognitive impairment (dementia). The only socio-demographic factor associated with cognitive impairment was age ≥ 40 years (odds ratio (OR) 4, 95% CI 1.2 - 13.4, P = 0.024). Conclusions The prevalence of cognitive impairment among patients with stroke is high. Increasing age is significantly associated with cognitive impairment. There is need for neurocognitive assessment programs among stroke patients and the introduction of rehabilitation services should target to maximize their functional recovery. © 2002-2012 African Journal of Neurological Sciences. All rights reserved.",adult;article;brain hemorrhage;brain infarction;cognitive defect;computer assisted tomography;cross-sectional study;disease association;disease severity;female;human;major clinical study;male;mass screening;Mini Mental State Examination;prevalence;questionnaire;teaching hospital;Uganda,"Mukisa, R.;Ddumba, E.;Musisi, S.;Kiwuwa, S. M.",2011,,,0,
2352,Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches: relationships with SNPs in ADNI,"Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE epsilon4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0.23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1.5 or < 0.67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0.001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0.01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*genetics;Amnesia/diagnosis/*genetics;Apolipoprotein E4/*genetics;Biomarkers/analysis;Cognition Disorders/diagnosis/*genetics;Executive Function;Female;Genetic Association Studies;Genetic Predisposition to Disease/*genetics;Humans;Male;Middle Aged;Polymorphism, Single Nucleotide/*genetics;Psychometrics","Mukherjee, S.;Trittschuh, E.;Gibbons, L. E.;Mackin, R. S.;Saykin, A.;Crane, P. K.",2012,Dec,10.1007/s11682-012-9207-y,0,
2353,"Human brain imaging of nicotinic acetylcholine alpha4beta2* receptors using [(18) F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways","Nicotinic acetylcholinergic receptors (nAChR's) have been implicated in several brain disorders, including addiction, Parkinson's disease, Alzheimer's disease and schizophrenia. Here we report in vitro selectivity and functional properties, toxicity in rats, in vivo evaluation in humans, and comparison across species of [(18) F]Nifene, a fast acting PET imaging agent for alpha4beta2* nAChRs. Nifene had subnanomolar affinities for halpha2beta2 (0.34 nM), halpha3beta2 (0.80 nM) and halpha4beta2 (0.83 nM) nAChR but weaker (27-219 nM) for hbeta4 nAChR subtypes and 169 nM for halpha7 nAChR. In functional assays, Nifene (100 muM) exhibited 14% agonist and >50% antagonist characteristics. In 14-day acute toxicity in rats, the maximum tolerated dose (MTD) and the no observed adverse effect level (NOAEL) were estimated to exceed 40 mug/kg/day (278 mug/m(2) /day). In human PET studies, [(18) F]Nifene (185 MBq; <0.10 mug) was well tolerated with no adverse effects. Distribution volume ratios (DVR) of [(18) F]Nifene in white matter thalamic radiations were approximately 1.6 (anterior) and approximately 1.5 (superior longitudinal fasciculus). Habenula known to contain alpha3beta2 nAChR exhibited low levels of [(18) F]Nifene binding while the red nucleus with alpha2beta2 nAChR had DVR approximately 1.6-1.7. Females had higher [(18) F]Nifene binding in all brain regions, with thalamus showing >15% than males. No significant aging effect was observed in [(18) F]Nifene binding over 5 decades. In all species (mice, rats, monkeys, and humans) thalamus showed highest [(18) F]Nifene binding with reference region ratios >2 compared to extrathalamic regions. Our findings suggest that [(18) F]Nifene PET may be used to study alpha4beta2* nAChRs in various CNS disorders and for translational research.",Rrid:scr_005279;Rrid:scr_007416;Rrid:scr_014214;cortical pathway;receptor selectivity;thalamus;translational research;white matter tracts,"Mukherjee, J.;Lao, P. J.;Betthauser, T. J.;Samra, G. K.;Pan, M. L.;Patel, I. H.;Liang, C.;Metherate, R.;Christian, B. T.",2018,Jan 1,,0,
2354,Neuro-psychiatric symptom associated with primary Sjogren's syndrome,"Neuro-psychiatric complications of primary Sjogren's syndrome (SjS) were studied on their frequency and characteristics of clinical signs in 150 patients of our clinic. Clinical symptoms and laboratory examinations were compared in the patients group complicated with neuro-psychiatric symptoms and the non-complicated group. Neuro-psychiatric symptoms (neuro SjS) were complicated with 63 patients (42.0%). Central nervous system (CNS) involvement were occurred in 47 patients (31.3%). In this group (CNS SjS), psychiatric complications were observed in 43 patients (28.7%), consisted with 29 cases of neurosis, 7 cases of depression, 6 cases of presenile dementia, and others. Nine patients (6.0%) in this group had neurologic involvement that were 3 cases of aseptic meningitis, 3 cases of neurogenic bladder, and each case of multiple infarction, multiple sclerosis, and others. These 9 patients showed more frequently positive results for rheumatoid factor, anti-SSA antibody, leucopenia, and lymphopenia, so this subgroup might be consisted of a small group which was resemble to systemic lupus erythematosus. Cranial nerve involvement, mainly injured in trigeminal nerve, and peripheral nerve involvement were complicated with 5 patients (3.3%) and 24 patients (16.0%), respectively. In neuro-psychiatric complicated group, mean age was older and dry mouth were more frequent (p less than 0.05) than non-complicated group. In psychiatric complicated group, mean age was older (p less than 0.01) and dry mouth were more frequent (p less than 0.05). In any groups of neuro-psychiatric complications, the frequency of any autoantibodies was not statistically different from non-complicated group. But, in the group of cranial nerve involvement, anti-RNP antibody was 60.0% positive (in non-complicated group, 17.2%: p less than 0.05). In CNS SjS group, magnetic resonance imaging (MRI) abnormalities were occurred in 8 of 13 patients. High intensity lesions in white matter on the T2-weighted examinations was characteristic, which showed lacnar infarctions or demyelinated lesions in MRI abnormalities. In CNS SjS, corticosteroid or immunosuppressant was not always necessary, because this complication was self-limited or enough controlled by minor-tranquilizer or anti-depressant. The character of onset in neuro SjS was chronic and neuro SjS was insidiously developing disease. And more studies including treatment on neuro SjS were needed.",Adult;Central Nervous System Diseases/ complications;Female;Humans;Magnetic Resonance Imaging;Male;Mental Disorders/ complications;Middle Aged;Peripheral Nervous System Diseases/ complications;Sjogren's Syndrome/complications/ psychology,"Mukai, M.;Sagawa, A.;Baba, Y.;Amasaki, Y.;Katsumata, K.;Yoshikawa, M.;Nakabayashi, T.;Watanabe, I.;Yasuda, I.;Fujisaku, A.;et al.",1990,Apr,,0,
2355,Amyloid Associated Intermittent Network Disruptions in Cognitively Intact Older Subjects: Structural Connectivity Matters,"Observations in animal models suggest that amyloid can cause network hypersynchrony in the early preclinical phase of Alzheimer's disease (AD). The aim of this study was (a) to obtain evidence of paroxysmal hypersynchrony in cognitively intact subjects (CN) with increased brain amyloid load from task-free fMRI exams using a dynamic analysis approach, (b) to investigate if and how hypersynchrony interferes with memory performance, and (c) to describe its relationship with gray and white matter connectivity. Florbetapir-F18 PET and task-free 3T functional and structural MRI were acquired in 47 CN (age = 70.6 +/- 6.6), 17 were amyloid pos (florbetapir SUVR >1.11). A parcellation scheme encompassing 382 regions of interest was used to extract regional gray matter volumes, FA-weighted fiber tracts and regional BOLD signals. Graph analysis was used to characterize the gray matter atrophy profile and the white matter connectivity of each subject. The fMRI data was processed using a combination of sliding windows, graph and hierarchical cluster analysis. Each activity cluster was characterized by identifying strength dispersion (difference between pos and neg strength) their maximal and minimal pos and neg strength rois and by investigating their distribution and association with memory performance and gray and white matter connectivity using spearman rank correlations (FDR p < 0.05). The cluster analysis identified eight different activity clusters. Cluster 8 was characterized by the largest strength dispersion indicating hypersynchrony. Its duration/subject was positively correlated with amyloid load (r = 0.42, p = 0.03) and negatively with memory performance (CVLT delayed recall r = -0.39 p = 0.04). The assessment of the regional strength distribution indicated a functional disconnection between mesial temporal structures and the rest of the brain. White matter connectivity was increased in left lateral and mesial temporal lobe and was positively correlated with strength dispersion in the cross-modality analysis suggesting that it enables widespread hypersynchrony. In contrast, precuneus, gray matter connectivity was decreased in the right fusiform gyrus and negatively correlated with high degrees of strength dispersion suggesting that progressing gray matter atrophy could prevent the generation of paroxysmal hypersynchrony in later stages of the disease.",Dti;amyloid;cognitively intact;functional connectivity;gray matter map;hypersynchrony;intermittent;resting state fMRI,"Mueller, S. G.;Weiner, M. W.",2017,,,0,
2356,Influences of lobar gray matter and white matter lesion load on cognition and mood,"Depressed mood is a frequent co-morbidity of dementia suggesting that they might share a common neuropathological substrate. Gray matter (GM) atrophy and white matter lesions (WML) have been described in both conditions. Our aims were to determine the relationship of GM and WML with cognition and depressed mood in the same population. Structural brain images were obtained from 42 controls, 20 Alzheimer's disease (AD) patients and 32 subjects with cognitive impairment/dementia due to subcortical cerebrovascular disease (vascCIND/IVD). Images were segmented to obtain lobar GM, white matter and WML volumes. Lobar WML had a negative effect on GM in all lobes in controls, on frontal, parietal and occipital GM in AD and on frontal GM in vascCIND/IVD. Frontal, temporal and hippocampal GM were associated with cognitive functions and frontal WML load with depressed mood. Cognitive function is associated with GM atrophy and depressed mood is associated with frontal WML. This indicates that although both often occur together, depressed mood and cognitive impairment have different pathological correlates.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Analysis of Variance;Atrophy;Cerebral Cortex/ pathology;Cognition Disorders/etiology/ pathology;Dementia, Vascular/complications;Depression/etiology/ pathology;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Psychiatric Status Rating Scales","Mueller, S. G.;Mack, W. J.;Mungas, D.;Kramer, J. H.;Cardenas-Nicolson, V.;Lavretsky, H.;Greene, M.;Schuff, N.;Chui, H. C.;Weiner, M. W.",2010,Feb 28,10.1016/j.pscychresns.2009.08.002,0,
2357,CADASIL with minimal symptoms after 60 years,"Introduction. CADASIL is a hereditary cerebral arteriopathy leading to progressive disability and dementia usually observed at 60 years. Observation. We report four patients aged >60 years with typical Notch3 mutations leading to CADASIL who did not have dementia or disability. Three of them presented with only transient neurological manifestations. MRI results showed extensive hyperintense signals in the white-matter on T2-weighted images contrasting with very few lacunar infarcts. Conclusion. These observations suggest that silent or symptomatic infarcts, which were rare in the present cases may be responsible for the clinical severity in this disorder. © 2006. Elsevier Masson SAS.",,"Mourad, A.;Levasseur, M.;Bousser, M. G.;Chabriat, H.",2006,September,,0,
2358,Comparison of qualitative and quantitative imaging characteristics of 11C PiB and 18F flutemetamol in normal control and Alzheimer's subjects,"INTRODUCTION: Neuritic amyloid plaques and neurofibrillary tangles, the hallmark pathologic lesions of Alzheimer's disease, are thought to develop before the symptoms of brain failure are clinically detectable. Imaging methods capable of detecting the presence of neuritic amyloid plaques should improve a clinician's ability to identify Alzheimer's disease during the earliest symptomatic phase and to identify at-risk individuals presymptomatically. Currently the best studied amyloid imaging ligand is [(11)C]Pittsburgh Compound B ([(11)C]PiB). However, the 20-minute half-life of this radiotracer limits its use. This study is designed to evaluate the performance characteristics of [(18)F]flutemetamol and to independently compare results to [(11)C]PiB in the same subjects. METHODS: Twenty-three subjects, 15 cognitively normal (NL) and 8 with a clinical diagnosis of Alzheimer's Dementia (AD), underwent [(11)C]PiB and [(18)F]flutemetamol PET scans within 28 days of study enrollment. We studied both normal and AD subjects to assess the uptake characteristics across a range of amyloid positivity. Blinded visual reads were conducted by five raters. Correlation analyses were performed between cortical SUVR for the two tracers and also between rater scores and SUVR for each tracer. Overall reader accuracy for classifying scans as amyloid positive or negative was determined for each tracer using SUVR classification as the standard. RESULTS: The linear correlation coefficient between global cortical SUVR for the two tracers was R(2) = 0.85, indicating that both tracers have similar retention characteristics. The two tracers were well correlated for rater-determined AD-like positivity (Cohen kappa = 0.82). Averaged visual ratings and global cortical SUVR disagreed on their classification in 2/23 [(11)C]PiB scans and 4/23 [(18)F]flutemetamol scans. CONCLUSIONS: [(11)C]PiB and [(18)F]flutemetamol have similar retention characteristics across a range of amyloid negative to positive subjects. Both tracers performed similarly when a standardized visual read technique was used to classify scans as amyloid-positive or amyloid-negative and correlated well with SUVR classifications. However, care in visual interpretation of amyloid positive versus amyloid negative regions should be taken, particularly in the case of [(18)F]flutemetamol when considering cortical vs. white-matter retention.",,"Mountz, J. M.;Laymon, C. M.;Cohen, A. D.;Zhang, Z.;Price, J. C.;Boudhar, S.;McDade, E.;Aizenstein, H. J.;Klunk, W. E.;Mathis, C. A.",2015,,10.1016/j.nicl.2015.10.007,0,
2359,Dementia risk after spontaneous intracerebral haemorrhage: A prospective cohort study,"Background: Dementia occurs in at least 10% of patients within 1 year after stroke. However, the risk of dementia after spontaneous intracerebral haemorrhage that accounts for about 15% of all strokes has not been investigated in prospective studies. We aimed to determine the incidence of dementia and risk factors after an intracerebral haemorrhage. Methods: We did a prospective observational cohort study in patients with spontaneous intracerebral haemorrhage from the Prognosis of Intracerebral Haemorrhage (PITCH) cohort who were admitted to Lille University Hospital, Lille, France. We included patients aged 18 years and older with parenchymal haemorrhage on the first CT scan. Exclusion criteria were pure intraventricular haemorrhage intracerebral haemorrhage resulting from intracranial vascular malformation, intracranial venous thrombosis, head trauma, or tumour; haemorrhagic transformation within an infarct; and referral from other hospitals. Median follow-up was 6 years. We studied risk factors (clinical and neuroradiological [MRI] biomarkers) of new-onset dementia as per a prespecified subgroup analysis, according to intracerebral haemorrhage location. Dementia diagnosis was based on the National Institute on Aging-Alzheimer's Association criteria for all-cause dementia. We did multivariable analyses using competing risk analyses, with death during follow-up as a competing event. Findings: From the 560 patients with spontaneous intracerebral haemorrhage enrolled in the PITCH cohort between Nov 3, 2004 and March 29, 2009, we included 218 patients (median age 67·5 years) without pre-existing dementia who were alive at 6 months follow-up. 63 patients developed new-onset dementia leading to an incidence rate of 14·2% (95% CI 10·0-19·3) at 1 year after intracerebral haemorrhage, and incidence reached 28·3% (22·4-34·5) at 4 years. The incidence of new-onset dementia was more than two times higher in patients with lobar intracerebral haemorrhage (incidence at 1 year 23·4%, 14·6-33·3) than for patients with non-lobar intracerebral haemorrhage (incidence at 1 year 9·2%, 5·1-14·7). Disseminated superficial siderosis (subhazard ratio [SHR] 7·45, 95% CI 4·27-12·99), cortical atrophy score (SHR per 1-point increase 2·61, 1·70-4·01), a higher number of cerebral microbleeds (SHR for >5 cerebral microbleeds 2·33, 1·38-3·94), and older age (SHR per 10-year increase 1·34, 1·00-1·79) were risk factors of new-onset dementia. Interpretation: There is a substantial risk of incident dementia in dementia-free survivors of spontaneous intracerebral haemorrhage our results suggest that underlying cerebral amyloid angiopathy is a contributing factor to the occurrence of new-onset dementia. Future clinical trials including patients with intracerebral haemorrhage should assess cognitive endpoints. Funding: French Ministry of Education, Research, and Technology, Adrinord, Inserm U1171.",adult;aged;article;brain atrophy;brain hemorrhage;brain tumor;cerebrovascular accident;cognitive defect;cohort analysis;congenital blood vessel malformation;dementia;female;follow up;France;groups by age;head injury;human;incidence;leukoaraiosis;major clinical study;male;National Institutes of Health Stroke Scale;nuclear magnetic resonance imaging;observational study;patient referral;priority journal;prospective study;risk factor;siderosis;transient ischemic attack;vascular amyloidosis;vein thrombosis,"Moulin, S.;Labreuche, J.;Bombois, S.;Rossi, C.;Boulouis, G.;Hénon, H.;Duhamel, A.;Leys, D.;Cordonnier, C.",2016,,10.1016/s1474-4422(16)00130-7,0,
2360,Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study,"BACKGROUND: Dementia occurs in at least 10% of patients within 1 year after stroke. However, the risk of dementia after spontaneous intracerebral haemorrhage that accounts for about 15% of all strokes has not been investigated in prospective studies. We aimed to determine the incidence of dementia and risk factors after an intracerebral haemorrhage. METHODS: We did a prospective observational cohort study in patients with spontaneous intracerebral haemorrhage from the Prognosis of Intracerebral Haemorrhage (PITCH) cohort who were admitted to Lille University Hospital, Lille, France. We included patients aged 18 years and older with parenchymal haemorrhage on the first CT scan. Exclusion criteria were pure intraventricular haemorrhage; intracerebral haemorrhage resulting from intracranial vascular malformation, intracranial venous thrombosis, head trauma, or tumour; haemorrhagic transformation within an infarct; and referral from other hospitals. Median follow-up was 6 years. We studied risk factors (clinical and neuroradiological [MRI] biomarkers) of new-onset dementia as per a prespecified subgroup analysis, according to intracerebral haemorrhage location. Dementia diagnosis was based on the National Institute on Aging-Alzheimer's Association criteria for all-cause dementia. We did multivariable analyses using competing risk analyses, with death during follow-up as a competing event. FINDINGS: From the 560 patients with spontaneous intracerebral haemorrhage enrolled in the PITCH cohort between Nov 3, 2004 and March 29, 2009, we included 218 patients (median age 67.5 years) without pre-existing dementia who were alive at 6 months follow-up. 63 patients developed new-onset dementia leading to an incidence rate of 14.2% (95% CI 10.0-19.3) at 1 year after intracerebral haemorrhage, and incidence reached 28.3% (22.4-34.5) at 4 years. The incidence of new-onset dementia was more than two times higher in patients with lobar intracerebral haemorrhage (incidence at 1 year 23.4%, 14.6-33.3) than for patients with non-lobar intracerebral haemorrhage (incidence at 1 year 9.2%, 5.1-14.7). Disseminated superficial siderosis (subhazard ratio [SHR] 7.45, 95% CI 4.27-12.99), cortical atrophy score (SHR per 1-point increase 2.61, 1.70-4.01), a higher number of cerebral microbleeds (SHR for >5 cerebral microbleeds 2.33, 1.38-3.94), and older age (SHR per 10-year increase 1.34, 1.00-1.79) were risk factors of new-onset dementia. INTERPRETATION: There is a substantial risk of incident dementia in dementia-free survivors of spontaneous intracerebral haemorrhage; our results suggest that underlying cerebral amyloid angiopathy is a contributing factor to the occurrence of new-onset dementia. Future clinical trials including patients with intracerebral haemorrhage should assess cognitive endpoints. FUNDING: French Ministry of Education, Research, and Technology, Adrinord, Inserm U1171.",,"Moulin, S.;Labreuche, J.;Bombois, S.;Rossi, C.;Boulouis, G.;Henon, H.;Duhamel, A.;Leys, D.;Cordonnier, C.",2016,Apr 28,10.1016/s1474-4422(16)00130-7,0,
2361,AIDS-associated progressive multifocal leukoencephalopathy revealed by new-onset seizures,"PURPOSE: To describe the clinical features of new-onset seizures in HIV- 1-infected persons with progressive multifocal leukoencephalopathy (PML), and to discuss potential mechanisms. PATIENTS AND METHODS: Forty-nine consecutive HIV-1-infected patients with PML attended our institutions between January 1988 and September 1993. We retrospectively analyzed cases with seizures as the presenting symptom of PML. RESULTS: Twenty percent of the HIV-1-infected patients with PML presented with new-onset seizures of various types, generalized or partial. None of them met the criteria of the AIDS dementia complex or had a concomitant opportunistic infection. Their mean CD4 cell count was <60/mm(3). Brain magnetic resonance imaging showed areas of increased signal intensity on T(2)-weighted images in 9 cases, and atrophy in only 1 case. Lesions most often involved subcortical white matter in parieto- occipital or frontal lobes, but 2 patients had posterior fossa lesions. Image-guided stereotactic brain biopsies in 8 cases and postmortem examination in 2 confirmed the diagnosis of PML. Typical histological lesions were observed in all cases, and positive immunolabelling of oligodendroglial nuclei was obtained in all cases with the polyclonal antibody directed against late SV40 antigens. Putative causative factors for the seizures include demyelinated lesions adjacent to the cerebral cortex acting as irritative foci, axonal conduction abnormalities, or disturbances of the neuron-glia balance. CONCLUSION: These cases illustrate that PML should be considered as a possible cause of new-onset seizures in patients with HIV-1 infection.",,"Moulignier, A.;Mikol, J.;Pialoux, G.;Fénelon, G.;Gray, F.;Thiebaut, J. B.",1995,1995,,0,
2362,A 49-year-old man with progressive bulbar palsy and respiratory failure,"We report a 49-year-old man with progressive bulbar palsy and respiratory failure. He was well until his 48 years of the age (December 1994) when he noted a difficulty in speaking in loud voice. In February, 1995, he noted regurgitation of foods to his nose and difficulty in his speech. He was admitted to our service in May 29, 1995. On admission, he was alert and oriented to all spheres and he was not demented. His higher cerebral functions were normal. In cranial nerves, he showed dysarthria and dysphagia; muscle atrophies were seen in the tongue, the bilateral sternocleidomastoid, supraspinatus, and infraspinatus muscles. Fasciculations were seen in these muscles. He showed no muscle weakness in his limbs except for the upper limb girdle muscles, no ataxia, no reflex abnormalities, nor sensory changes. EMG showed neurogenic changes in the affected muscles. MRI of the brain and the spinal cord was entirely normal. He was discharged for out patient follow-up, however, in October of 1995, he noted difficulty in swallowing solid foods. Gastrostomy was placed and he was discharged to his home. In February 11th of 1996, he was found unresponsive and brought into the ER of our hospital. On admission, he was comatose without spontaneous respiration. BP could not be obtained. He was immediately intubated and artificial ventilation was started. On the following morning, he became alert and he was not demented. He continued to show marked dysarthria and dysphagia; again no weakness was noted in the distal parts of the upper and lower extremities. Laboratory examination showed increase in serum CK to 2,173 IU/L and amylase to 2,032 IU/L. He was extubated on February 15th, however, his spontaneous respiration was not suffice to maintain his blood gas. According to his will, he was not placed on respirator and he died on February 24th, 1996. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had ALS. Although no upper neuron signs were observed clinically, it is not uncommon to see degeneration in the corticospinal tract in post-mortem examination. The question was what might have been the cause of increase in CK and amylase. Many participants thought that they were secondary to multiple organ failure due to prolonged hypoxic state at his last admission; other possibilities raised included acute myocardial infarction and acute bowel necrosis. Post- mortem examination revealed muscle atrophy in the facial, lingual, cervical, intercostal, and the upper limb girdle areas. The lungs were unremarkable except for old organized pneumonic foci in the right middle and lower lobes. Marked to moderate congestion was seen in many internal organs, however, no other gross abnormality was found. It was thought that respiratory palsy itself was the direct cause of his agonal event. In the spinal cord, the anterior horns showed various degree of neuronal loss and gliosis. No clear evidence of pyramidal tract degeneration was seen at the light microscope level. Lower brain stem motor neurons were markedly reduced. But no Bunina body was found. The substantia nigra showed moderate degree of neuronal loss and extraneuronal neuromelanins. The locus coeruleus showed similar but milder changes. The degree of nigral degeneration appeared to be well beyond those which could be seen in usual ALS patients. The question was whether or not this patient might have been in an early stage of the extended form of ALS.",amylase;creatine kinase;adult;amyotrophic lateral sclerosis;article;case report;clinical feature;facial nerve paralysis;histopathology;human;human tissue;male;neuropathology;respiratory failure,"Motoi, Y.;Satoh, K. I.;Matsumine, H.;Wakiya, W.;Mori, H.;Shirai, T.;Kondo, T.;Mizuno, Y.",1998,,,0,
2363,Fornix infarction and Korsakoff dementia after coiling of a large anterior communicating artery aneurysm,,adult;anterior communicating artery aneurysm;anterograde amnesia;article;brain angiography;brain infarction;case report;dysphoria;fornix infarction;human;Korsakoff psychosis;male;neuropsychological test;nuclear magnetic resonance imaging;paramnesia;postoperative complication;priority journal;retrograde amnesia;risk assessment;surgical approach;surgical technique,"Mosimann, P. J.;Saint-Maurice, J. P.;Lenck, S.;Puccinelli, F.;Houdart, E.",2012,,,0,
2364,Sex differences in Alzheimer risk,"Objective: This observational multimodality brain imaging study investigates emergence of endophenotypes of late-onset Alzheimer disease (AD) risk during endocrine transition states in a cohort of clinically and cognitively normal women and age-matched men. Methods: Forty-two 40- to 60-year-old cognitively normal women (15 asymptomatic perimenopausal by age [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men were examined. All patients had volumetric MRI, 18 F-fluoro-2-deoxyglucose (FDG)-PET (glucose metabolism), and Pittsburgh compound B-PET scans (β-amyloid [Aβ] deposition, a hallmark of AD pathology). Results: As expected, the MENO group was older than the PERI and CNT groups. Otherwise, groups were comparable on clinical and neuropsychological measures and APOE4 distribution. Compared to CNT women and to men, and controlling for age, PERI and MENO groups exhibited increased indicators of AD endophenotype, including hypometabolism, increased Aβ deposition, and reduced gray and white matter volumes in AD-vulnerable regions (p < 0.001). AD biomarker abnormalities were greatest in MENO, intermediate in PERI, and lowest in CNT women (p < 0.001). Aβ deposition was exacerbated in APOE4-positive MENO women relative to the other groups (p < 0.001). Conclusions: Multimodality brain imaging indicates sex differences in development of the AD endophenotype, suggesting that the preclinical AD phase is early in the female aging process and coincides with the endocrine transition of perimenopause. These data indicate that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.",amyloid beta protein;APOE4 protein;fluorodeoxyglucose f 18;glucose;high density lipoprotein;low density lipoprotein;Pittsburgh compound B;protein;triacylglycerol;unclassified drug;adult;aging;Alzheimer disease;article;brain atrophy;brain size;climacterium;clinical article;cognition;cohort analysis;comparative study;controlled study;endophenotype;female;folic acid blood level;glucose metabolism;gray matter;human;male;menopause;menstrual cycle;neuroimaging;nuclear magnetic resonance imaging;observational study;positron emission tomography;postmenopause;premenopause;priority journal;Quantitative Insulin Sensitivity Check Index;risk factor;sex difference;white matter,"Mosconi, L.;Berti, V.;Quinn, C.;McHugh, P.;Petrongolo, G.;Varsavsky, I.;Osorio, R. S.;Pupi, A.;Vallabhajosula, S.;Isaacson, R. S.;De Leon, M. J.;Brinton, R. D.",2017,,10.1212/wnl.0000000000004425,0,
2365,The role of the clinician in interpreting conventional neuroimaging findings in migraine patients,"Changes in cerebral white matter at CT or MRI have been reported in patients with migraine, especially in those with migraine with aura. Similar pictures may be present in asymptomatic subjects, and their nature is not completely understood, but their infarct-like nature is strongly suggested. Clinicians play an important role in the evaluation of those migraine patients in whom these nonspecific abnormalities are present. We suggest ruling out specific syndromes in which migraine attacks are associated with white matter changes (CADASIL, MELAS, multiple sclerosis and central nervous system vasculitis), as well as evaluating the presence of different vascular risk factors (genetic prothrombotic factors, patent foramen ovale, use of oral contraceptives, etc.). Their possible causative role in MRI lesions and in enhancing the risk of a negative clinical evolution must be considered in each individual case. © Springer-VerlagItalia 2007.",oral contraceptive agent;article;CADASIL;central nervous system;computer assisted tomography;drug use;heart atrium septum defect;heredity;human;MELAS syndrome;migraine;migraine with aura;multiple sclerosis;neuroimaging;nuclear magnetic resonance imaging;physician attitude;risk factor;vasculitis;white matter,"Moschiano, F.;D'Amico, D.;Stefano, M.;Rocca, N.;Bussone, G.",2007,,,0,
2366,Mutational Screening of NOTCH3 Gene Reveals Two Novel Mutations: Complexity of CADASIL Diagnosis,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary vascular disease with neurological manifestations. The classical clinical course is relentlessly progressive with early transient ischaemic attacks (TIA) or strokes, dementia and finally death in the mid-1960s. The disorder is inherited in an autosomal dominant fashion, with high penetrance and broad variable clinical course even within family. It is caused by mutations in the NOTCH3 gene; all causative mutations result in gain or loss of a cysteine residue within the extracellular domain, with exons 3 and 4 reported as hot spot mutational sites. Mutation analysis of the NOTCH3 gene was performed through direct sequencing of the 2–23 exons containing all EGF-like domains. Patients underwent genetic counselling pre and post testing. Here, we report two novel mutations located in exons 6 and 15 of the NOTCH3 gene; clinical description for the probands and for available relatives is enclosed. No reliable data on incidence or prevalence rates of this disease are available: it is therefore essential that the diagnosis is obtained in all suspected cases through the extensive analysis of the NOTCH3 gene and that all cases are brought to the attention of the scientific community.",genomic DNA;Notch3 receptor;adult;aged;article;brain ischemia;CADASIL;case report;computer assisted tomography;disease course;exon;female;gene mutation;genetic association;genetic counseling;genetic screening;human;male;middle aged;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;nucleotide sequence;phenotype;transient ischemic attack;white matter lesion;X chromosome,"Mosca, L.;Rivieri, F.;Tanel, R.;Bonfante, A.;Burlina, A.;Manfredini, E.;Primignani, P.;Gesu, G. P.;Marocchi, A.;Penco, S.",2014,,,0,
2367,High normal fasting blood glucose is associated with dementia in Chinese elderly,"BACKGROUND: Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. METHODS: Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients, and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. RESULTS: Controlling for age, gender, education, body mass index, Hachinski Ischemic Score, magnetic resonance imaging (MRI) stroke, and normalized brain, hippocampal, and white matter hyperintensity MRI volumes; higher FBG was associated with dementia versus aMCI status (OR = 3.13; 95% CI, 1.28-7.69). This association remained (OR = 7.75; 95% CI, 1.10-55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, gender, and education, a significant association with FBG also was seen (OR = 1.83; 95% CI, 1.09-3.08), but it was lost when vascular covariates were added to the model. FBG was not associated with aMCI status versus NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (P = .003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (chi(2) = 13.9, P < .001). CONCLUSIONS: Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia.",Aged;Blood Glucose/biosynthesis/ metabolism;Case-Control Studies;Comorbidity;Cross-Sectional Studies;Dementia/ blood/ complications/diagnosis;Diabetes Complications/ blood/ complications/diagnosis;Female;Humans;Hyperglycemia/ blood/ complications/diagnosis;Male;Risk Factors,"Mortimer, J. A.;Borenstein, A. R.;Ding, D.;Decarli, C.;Zhao, Q.;Copenhaver, C.;Guo, Q.;Chu, S.;Galasko, D.;Salmon, D. P.;Dai, Q.;Wu, Y.;Petersen, R.;Hong, Z.",2010,Nov,10.1016/j.jalz.2010.03.017,0,
2368,The nun study: Risk factors for pathology and clinical-pathologic correlations,"The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology. © 2012 Bentham Science Publishers.",apolipoprotein E4;biological marker;aged;Alzheimer disease;article;autopsy;brain infarction;brain size;cerebrovascular disease;cognition;controlled study;correlational study;dementia;disease severity;educational status;female;geriatric patient;hippocampus;human;human tissue;linguistics;major clinical study;memory disorder;neurofibrillary tangle;neuroimaging;neurologic examination;neuropathology;nuclear magnetic resonance imaging;outcome assessment;priority journal;risk assessment;risk factor,"Mortimer, J. A.",2012,,,0,
2369,Spatial Distribution of Cerebral White Matter Lesions Predicts Progression to Mild Cognitive Impairment and Dementia,"Context: White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years. Methods: In 426 healthy subjects from a cohort of community-dwelling people aged 65 years and over (ESPRIT Project), standardized cognitive and neurological evaluations were repeated after 2, 4 and 7 years. Patterns of WML were computed with a supervised data mining approach (decision trees) using the regional WML volumes (frontal, parietal, temporal, and occipital regions) and the total WML volume estimated at baseline. Cox proportional hazard models were then constructed to study the association between WML patterns and risk of MCI/dementia. Results: Total WML volume and percentage of WML in the temporal region proved to be the best predictors of progression to MCI and dementia. Specifically, severe total WML load with a high proportion of lesions in the temporal region was significantly associated with the risk of developing MCI or dementia. Conclusions: Above a certain threshold of damage, a pattern of WML clustering in the temporal region identifies individuals at increased risk of MCI or dementia. As this WML pattern is observed before the onset of clinical symptoms, it may facilitate the detection of patients at risk of MCI/dementia. © 2013 Mortamais et al.",apolipoprotein E4;aged;article;brain atrophy;brain infarction;brain size;cognition;cohort analysis;community living;controlled study;decision tree;dementia;disease course;education;female;frontal lobe;genotype;hippocampus;human;incidence;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;prediction;risk factor;symptomatology;temporal lobe;white matter lesion,"Mortamais, M.;Reynes, C.;Brickman, A. M.;Provenzano, F. A.;Muraskin, J.;Portet, F.;Berr, C.;Touchon, J.;Bonafé, A.;le Bars, E.;Maller, J. J.;Meslin, C.;Sabatier, R.;Ritchie, K.;Artero, S.",2013,,,0,
2370,Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia,"OBJECTIVES: Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (</=8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. RESULTS: The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (</=8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.",Aged;Brain/pathology;Dementia/ etiology/pathology;Educational Status;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ etiology/pathology;Neuroimaging;Organ Size;Risk Factors;White Matter/ pathology,"Mortamais, M.;Portet, F.;Brickman, A. M.;Provenzano, F. A.;Muraskin, J.;Akbaraly, T. N.;Berr, C.;Touchon, J.;Bonafe, A.;le Bars, E.;Menjot de Champfleur, N.;Maller, J. J.;Meslin, C.;Sabatier, R.;Ritchie, K.;Artero, S.",2014,Nov,10.1016/j.jagp.2013.06.002,0,
2371,Delayed cerebral radiation necrosis,"The clinical features and long-term outcome of seven patients with delayed cerebral radiation necrosis (DCRN) are described. Radiotherapy had been given for pituitary tumour (1), astrocytoma (2), pinealoma (2), craniopharyngioma (1) and parotid carcinoma (1). The mean latency to onset of the first neurological symptoms was 22 months (range 6-40 months), and mean duration of follow-up was 86 months (range 60-126). Three patients died at a mean of 84 months after radiotherapy (range 62-98). A fourth patient probably died from metastatic disease. Three patients remain alive, albeit severely disabled, after 5-10 years. The illness typically ran a stepwise course, with fits and stroke-like episodes occurring against a background of progressive dementia and somnolence. CT and MRI scans showed progressive ventricular dilatation associated with cerebral atrophy and diffuse or focal changes in the white matter. Four patients had had two or more neurosurgical procedures after the radiotherapy. In only one of the seven patients was the diagnosis made at presentation. DCRN produces a distinctive clinical picture, yet remains a poorly recognized complication of cranial irradiation.",adolescent;adult;article;astrocytoma;brain necrosis;brain ventricle dilatation;clinical article;clinical feature;computer assisted tomography;craniopharyngioma;dementia;female;follow up;human;hypophysis tumor;latent period;male;neurologic disease;nuclear magnetic resonance imaging;parotid gland carcinoma;pineal body tumor;priority journal;prognosis;radiation necrosis;somnolence,"Morris, J. G. L.;Grattan-Smith, P.;Panegyres, P. K.;O'Neill, P.;Soo, Y. S.;Langlands, A. O.",1994,,,0,
2372,"Binswanger's disease or artifact: a clinical, neuroimaging, and pathological study of periventricular white matter changes in Alzheimer's disease",,Aged;Alzheimer Disease/*diagnosis/pathology;Brain/*pathology;Dementia/*diagnosis/pathology;Female;Humans;*Magnetic Resonance Imaging;Male,"Morris, J. C.;Gado, M.;Torack, R. M.;McKeel, D. W., Jr.",1990,,,0,
2373,"Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer's disease mild cognitive impairment, and elderly controls","We introduce a new method for brain MRI segmentation, called the auto context model (ACM), to segment the hippocampus automatically in 3D T1-weighted structural brain MRI scans of subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In a training phase, our algorithm used 21 hand-labeled segmentations to learn a classification rule for hippocampal versus non-hippocampal regions using a modified AdaBoost method, based on ∼ 18,000 features (image intensity, position, image curvatures, image gradients, tissue classification maps of gray/white matter and CSF, and mean, standard deviation, and Haar filters of size 1 × 1 × 1 to 7 × 7 × 7). We linearly registered all brains to a standard template to devise a basic shape prior to capture the global shape of the hippocampus, defined as the pointwise summation of all the training masks. We also included curvature, gradient, mean, standard deviation, and Haar filters of the shape prior and the tissue classified images as features. During each iteration of ACM - our extension of AdaBoost - the Bayesian posterior distribution of the labeling was fed back in as an input, along with its neighborhood features as new features for AdaBoost to use. In validation studies, we compared our results with hand-labeled segmentations by two experts. Using a leave-one-out approach and standard overlap and distance error metrics, our automated segmentations agreed well with human raters; any differences were comparable to differences between trained human raters. Our error metrics compare favorably with those previously reported for other automated hippocampal segmentations, suggesting the utility of the approach for large-scale studies. © 2008 Elsevier Inc. All rights reserved.",,"Morra, J. H.;Tu, Z.;Apostolova, L. G.;Green, A. E.;Avedissian, C.;Madsen, S. K.;Parikshak, N.;Hua, X.;Toga, A. W.;Jack Jr, C. R.;Weiner, M. W.;Thompson, P. M.",2008,15,,0,
2374,Cognitive decline and hypersomnolence: Thalamic manifestations of a tentorial dural arteriovenous fistula (dAVF),"Background: Intracranial dural arteriovenous fistulas (dAVFs) often present with pulsatile tinnitus, orbital congestion, and headache. Occasionally, they present with focal neurologic deficits, a dementia-like syndrome, hemorrhage, or ischemic infarction. Methods: This study is based on the case of a 71-year-old gentleman who presented with 6 months of progressive forgetfulness, inattention, and hypersomnolence. Four weeks prior to presentation, he developed symptoms of left-sided pain, numbness, and worsening weakness. Neurologic examination demonstrated hypersomnolence, a score of 30/38 on the Kokmen Short Test of Mental Status, and left hemiparesis. MRI brain revealed bilateral thalamic T2 hyperintensities with associated enhancement. MR venogram (MRV) showed a vascular malformation in the posterior fossa and occlusion of the straight sinus. Conventional cerebral angiogram confirmed a tentorial dAVF. The dAVF was definitively treated with transarterial embolization, followed by clip ligation of the arterialized draining vein. Twelve weeks later, there was clinical resolution of left hemiparesis and improvement in cognitive status. MRI revealed complete resolution of the thalamic hyperintensities. MRV demonstrated recanalization of the straight sinus. Results: Intracranial dAVFs are uncommon but potentially life-threatening acquired vascular malformations. The initiating factor is venous hypertension, causing retrograde flow, venous congestion, ischemia, and sometimes infarction. The spectrum of clinical manifestations in dAVFs reflects the degree of venous congestion present. If retrograde venous flow is surgically obliterated, then venous hypertension may be reversible. Bilateral thalamic venous congestion can present as a thalamic dementia. Conclusion: We conclude that intracranial dAVFs with thalamic venous congestion should be considered in the diagnostic differential for patients who present with subacute cognitive decline and T2 hyperintense thalamic signal change. © 2012 Springer Science+Business Media, LLC.",aged;article;artificial embolism;attention disturbance;blood vessel clip;brain angiography;case report;cerebellum;cognitive defect;contrast enhancement;craniectomy;daytime somnolence;differential diagnosis;diffusion weighted imaging;dural arteriovenous fistula;embolization coil;follow up;hemiparesis;human;limb weakness;magnetic resonance angiography;male;nuclear magnetic resonance imaging;pain;paresthesia;peroneus nerve paralysis;posterior fossa;priority journal;somnolence;straight sinus;susceptibility weighted imaging;tentorial dural arteriovenous fistula;thalamus;transverse sinus;vein ligation;venous congestion;white matter;Onyx,"Morparia, N.;Miller, G.;Rabinstein, A.;Lanzino, G.;Kumar, N.",2012,,,0,
2375,[Differential diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy] Differentsial'naia diagnostika tserebral'noi autosomno-dominantnoi arteriopatii s podkorkovymi infarktami i leikoentsefalopatiei,"Cerebral autosomal dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) is an inherited CNS disease, which is caused by mutations in the NOTCH3 gene. Selective disorders of small vessels underlie the disease pathogenesis. Clinically CADASIL is characterized by headaches, multiple stroke-like disorders (in most cases transient ischemic attacks and lacunar strokes), and different focal neurological symptoms and dementia. There are specific MRI signs of the disease: multiple lacunar infarctions located in the basal ganglia, brain steam and cerebellum, focal lesions of temporal poles, capsula externa, periventricular and subcortical areas; diffuse white matter changes and leukoaraiosis can be observed as well. The differential diagnosis of CADASIL is made with many diseases, which are manifested by multiple brain matter lesions, including demyelinating disorders. It should be taken into account that CADASIL is characterized by headaches as one of the initial symptoms, multiple lacunar and diffuse brain matter lesions based on MRI data with an absence of atherosclerosis and arterial hypertension. Family history and autosomal dominant mode of inheritance is also typical of CADASIL. Detection of the NOTCH3 gene mutation is necessary for the definite diagnosis of CADASIL.",Cadasil;Mri;Notch3;differential diagnosis;leucoencephalopathy;multiple sclerosis,"Moroz, A. A.;Abramycheva, N. Y.;Stepanova, M. S.;Konovalov, R. N.;Timerbaeva, S. L.;Illarioshkin, S. N.",2017,,,0,
2376,"Carotid atherosclerosis, silent ischemic brain damage and brain atrophy: A systematic review and meta-analysis","BACKGROUND: The widespread use of brain imaging has led to increased recognition of subclinical brain abnormalities, including white matter hyperintensities (WMH) and silent brain infarctions (SBI), which have a vascular origin, and have been associated to a high risk of stroke, disability and dementia. Carotid atherosclerosis (CA) may be causative in the development of WMH, SBI and eventually brain atrophy. Aim of the present systematic review and meta-analysis was to assess the existing evidence linking CA to WMH, SBI and brain atrophy. METHODS: The relation between CA and WMH, SBI and brain atrophy was investigated through the systematic search of online databases up to September 2015 and manual searching of references and related citations. Pooled estimates were calculated by random-effects model, using restricted maximum likelihood method with inverse variance weighting method. RESULTS: Of the 3536 records identified, fifteen were included in the systematic review and 9 were found to be eligible for the meta-analysis. CA was significantly associated with the presence of WMH (Odds Ratio, OR 1.42, confidence interval, CI 1.22-1.66, p<0.0001) and of SBI (OR 1.89, CI 1.46-2.45, p<0.0001). No meta-analysis could be performed for the relation between CA and brain atrophy due to the lack of suitable studies. CONCLUSIONS: CA was found to be associated to WMH and SBI. While no causative association can be inferred from the available data, the presence of carotid plaque may be considered a significant risk factor for subclinical cerebral damage.",Brain atrophy;Carotid atherosclerosis;Leukoaraiosis;Meta-analysis;Silent brain infarction,"Moroni, F.;Ammirati, E.;Magnoni, M.;D'Ascenzo, F.;Anselmino, M.;Anzalone, N.;Rocca, M. A.;Falini, A.;Filippi, M.;Camici, P. G.",2016,Aug 13,10.1016/j.ijcard.2016.08.234,0,
2377,Diffusion-weighted imaging of acute excitotoxic brain injury,"DW imaging is useful for evaluating cytotoxic edema due to excitotoxic brain injury, a common final pathway for various neurologic diseases. The severity (reversibility) and distribution are different in various neurologic diseases (in terms of cell types, initial insults, and their mechanisms) and in patients of differing ages (with factors such as the age-dependent distribution of receptors and the maturity of the blood-brain barrier). Excitotoxic amine receptors are present in neurons, axons, glial cells, and myelin sheaths. Astrocytes and myelin sheaths, which protect synapses and axons, swell after absorbing excessive glutamate. Such cytotoxic edema seems to be transient and resolves on follow-up MR imaging. Energy failure (impaired reuptake of glutamate) is the initial insult during infarction and HIE. It usually causes irreversible excitotoxic brain injury and typically results in necrosis and atrophy. Secondary degeneration, such as wallerian degeneration, seems to be related to excitotoxic circuits via the synapses or axons. Excessive release of glutamate can cause cytotoxic edema in conditions such as seizure, infection, demyelination, and toxic metabolic disease. Such cytotoxic edema is due to excitotoxic injury with less energy failure; this type occasionally resolves on follow-up MR imaging. Diffuse axonal injury can cause the leakage of glutamate from the axon at the node of Ranvier. The distribution of lesions associated with status epilepticus seems to be related to the distribution of NMDA receptors. The severity and distribution in HIE, shaken baby syndrome, and neonatal herpes encephalitis seems to be related to increased vulnerability of the developing brain to excitotoxic injury. In organic acid disorders, structurally similar substances can cause excitotoxic injury. Receptor dysfunction can occur in metabolic conditions (phenylketonuria) and degenerative diseases (CJD). Glutamate receptor antagonists may offer attractive possibilities for future therapy as possible neuroprotectants in the management of these diseases. © American Society of Neuroradiology.",,"Moritani, T.;Smoker, W. R. K.;Sato, Y.;Numaguchi, Y.;Westesson, P. L. A.",2005,2005,,0,
2378,Dementia in Patients with Central Nervous System Mycosis,"Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.",,"Morita, A.;Ishihara, M.;Konno, M.",2016,Apr,10.11477/mf.1416200402,0,
2379,"A 60-year-old woman with progressive cerebellar ataxia, myoclonus, and dementia","We report a 60-year-old woman with progressive ataxia, myoclonus, choreoathetosis, and dementia. She was well until 27 years of the age when she noted an onset of gait disturbance and speech disturbance. She noted abnormal involuntary movements in her four limbs at 42 years of the age. Her symptoms had progressively become worse and she fell down frequently by her 52 years of the age. In addition, her family members noted gradual decline in her intelligence. She was admitted to our hospital in February of 1993 when she was 57-year-old. On admission, she showed dementia, scanning speech, ataxic gait, limb ataxia, action myoclonus, and choreic movements which involved her four limbs. Deep tendon reflexes were slightly exaggerated in the lower limbs; no Babinski sign was noted. Sensation was intact. Laboratory findings were unremarkable. Cerebral MRI revealed atrophy of the cerebellar cortex, superior cerebellar peduncle, brain stem, and the cerebral cortex; the third ventricle and the lateral ventricles were dilated; furthermore, T2- high signal lesions were seen in the cerebral white matter and in the pontine base. Her clinical course was one of the progressive deterioration of her ataxia, involuntary movements, and dementia. She expired on April 24, 1996 when she was 60-year-old. She was discussed in a neurologic CPC and the chief discussant arrived at the conclusion that the patient had dentatorubral- pallidoluysian atrophy. A minor opinion was that she might have bad myoclonus epilepsy with ragged-red fibers. Postmortem examination revealed atrophy, gliosis, and neuronal loss in the external segment of the globus pallidus, subthalamic nucleus, red nucleus, and in the dentate nucleus. In addition, the gracil and cuneiform nuclei showed neuronal loss and spheroid formation; the spinocerebellar tracts were retained. The substantia nigra and the locus coeruleus were intact. No ragged red fibers were seen in the muscle biopsy specimen taken in February, 1993. The neuropathologic findings were consistent with the diagnosis of dentatorubral-pallidoluysian atrophy.",adult;article;autopsy;brain atrophy;brain ventricle dilatation;case report;cerebellar ataxia;choreoathetosis;clinical examination;dementia;dentatorubropallidoluysian atrophy;female;gait disorder;human;myoclonus;nuclear magnetic resonance imaging;speech disorder,"Morikawa, N.;Mori, H.;Sumino, S.;Kodera, M.;Shirai, T.;Kondo, T.;Mizuno, Y.",1997,,,0,
2380,To what extent has the pathophysiology of normal-pressure hydrocephalus been clarified?,"The causes and pathophysiology of idiopathic normal-pressure hydrocephalus (NPH) still remain poorly understood. We reviewed the recent pertinent literature on NPH from the past 3 years (1994- 1996) in this journal [Crit Rev Neurosurg (1997) 7:263-275] and here review further manuscripts that appeared mainly in 1997. Recent investigations suggest that idiopathic NPH may be a primary cerebral parenchymal disease rather than a disorder of cerebrospinal fluid (CSF) absorption. The pathophysiology of idiopathic NPH has a wide spectrum ranging from purely hydrodynamic problems owing to a CSF absorption defect to parenchymal changes caused by hemodynamic problems owing to ischemic vascular risk factors. Magnetic resonance imaging (MRI) of NPH frequently shows ischemic vas-cular encephalopathy. NPH may coexist with subcortical white matter vascular encephalopathy, because Binswanger's encephalopathy and idiopathic NPH share common clinical symptoms. Most patients with suspected NPH may suffer from both problems. Because of MRI findings of suspected NPH, ischemic parenchymal changes caused by vasculopathy have been receiving attention. Brain biopsy findings of suspected NPH suggest the presence of parenchymal changes caused by vasculopathy such as arteriosclerosis. Patients with brain biopsy findings of Alzheimer's disease may benefit from shunting. Pathological changes seen by brain biopsy are not specific for NPH. The information accumulated so far about NPH shows a wide clinical spectrum and multifactorial etiology. Therefore, patients with NPH are inhomogeneous, and this makes it difficult to diagnose and select patients for shunting.",,"Mori, K.;Mima, T.",1998,Jul 20,,0,
2381,Decreased myocardial uptake of meta-iodobenzylguanidine in an autopsy-confirmed case of corticobasal degeneration with Lewy bodies restricted to the sympathetic ganglia,"We report on an autopsy case of corticobasal degeneration (CBD) with Lewy bodies in only the sympathetic ganglia. A 79-year-old man showed walking disturbance as an initial symptom, and developed dementia and bradykinesia within the next 2 years. Neurological examination revealed parkinsonism-like akinesia and rigidity in the trunk and neck without resting tremor. Brain magnetic resonance imaging showed frontal lobe atrophy predominantly on the right side. Cardiac uptake of meta-iodobenzylguanidine (MIBG) was reduced (H/M ratio: 1.14). A diagnosis of dementia with Lewy bodies (DLB) was made, but L-dopa treatment was not effective. Seven years later he died of pneumonia. On pathological examination, the frontal cortex and white matter were degenerated, predominantly on the right side. Gallyas-Braak silver staining and AT-8 ¡revealed neurofibrillary tangles, pretangles, argyrophilic threads, and astrocytic plaques in the cerebral cortex and basal ganglia, confirm~ing the diagnosis of CBD. Lewy bodies, which were not seen in the central nervous system, were seen only in the sympathetic ganglia, and a severe loss of nerve fibers was apparent in the sympathetic nerve endings in the heart MIBG is currently used to differentiate DLB from other parkinsonisms, such as CBD, multiple system atrophy, and progressive supranuclear palsy, because reduced cardiac uptake of MIBG represents a pathological change in the sympathetic nerve endings in the heart However, the distribution of Lewy bodies cannot be determined from this finding. Thus, MIBG should not be used alone to confirm a diagnosis of DLB; other neurodegenerative diseases with incidental Lewy body disease, as in the present case, must be also considered.",,"Mori, K.;Iwasaki, Y.;Ito, M.;Mimuro, M.;Yoshida, M.",2012,June,,0,
2382,Individualized pterional keyhole clipping surgery based on a preoperative three-dimensional virtual osteotomy technique for unruptured middle cerebral artery aneurysm,"Objective: Individualized surgical simulation using three-dimensional (3D) imaging to allow safe performance of clipping surgery for unruptured middle cerebral artery (MCA) aneurysm via pterional keyhole mini-craniotomy was performed in 100 consecutive patients. Methods: 3D images were reconstructed of the skin, skull, cerebral arteries and veins, and aneurysm. The size, shape, and location of the scheduled keyhole and the patients head position were individually optimized using this preoperative simulation system. The site of opening of the sylvian fissure was also preoperatively determined according to the spatial relationships between the aneurysm and sylvian veins. 110 pterional keyhole clipping surgeries were consecutively performed in 100 patients. Results: The mean diameter of the pterional keyhole was 252mm. Magnetic resonance imaging detected lacunar infarction in 4 cases (3.6%) but no other abnormalities. 1 patient suffered a reversible ischemic neurological deficit and 1 patient (79 years old) showed mild dementia. The modified Rankin scale at 3 months after the operation was grade 0 in all cases except 1 patient with mild dementia (grade 1). Mini-mental state examination, Hamilton rating scale for depression, and Beck depression inventory were all significantly improved (p<0.01) after the operations. Conclusion: Pterional keyhole clipping surgery based on careful surgical simulation with 3D images is a safe and less invasive means to treat relatively small unruptured MCA aneurysms. © Georg Thieme Verlag KG Stuttgart • New York.",,"Mori, K.;Esaki, T.;Yamamoto, T.;Nakao, Y.",2011,2011,,0,
2383,Symmetric temporal abnormalities on MR imaging in amyotrophic lateral sclerosis with dementia,"BACKGROUND AND PURPOSE: Our aim was to clarify imaging findings of amyotrophic lateral sclerosis with dementia (ALSD). MATERIALS AND METHODS: T2-weighted MR images (T2WI) of 3 patients with ALSD (2 men, 1 woman; 58-71 years of age) and 21 patients with ALS without dementia (12 men, 9 women; 46-74 years of age) were examined for frontotemporal lobar atrophy and signal-intensity alterations in the white matter of the anterior temporal lobes, corticospinal tracts (CST), and precentral gyri and in precentral cortices. The brain of one of the patients with ALSD was examined at autopsy. RESULTS: All patients with ALSD showed bilateral frontotemporal atrophy mostly with temporal lobe dominance. In the ALSD group, T2WI demonstrated hyperintensity in the subcortical white matter on the medial side of the anterior temporal lobes, whereas in the group without dementia, none showed this imaging finding. MR images demonstrated no abnormal signal-intensity changes in CST in the internal capsule or the brain stem in the ALSD group. In the group without dementia, 6 patients (28.6%) showed this imaging finding. In neuropathologic examinations of the brain of 1 patient with ALSD, myelin-stained sections of the brain demonstrated loss of myelin in the subcortical white matter on the medial side of the anterior temporal white matter. CONCLUSIONS: A symmetric pattern of frontotemporal atrophy and anteromedial subcortical hyperintensities in the temporal lobes on T2WI could be characteristic of ALSD.",Aged;Amyotrophic Lateral Sclerosis/ diagnosis/pathology;Atrophy;Female;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Temporal Lobe/ pathology,"Mori, H.;Yagishita, A.;Takeda, T.;Mizutani, T.",2007,Sep,10.3174/ajnr.A0624,0,
2384,Functional brain imaging as a surrogate marker in vascular cognitive impairment,"Functional brain imaging represents cerebrovascular status, neuronal status, and neuronetwork status, and plays an increasingly important role in the evaluation of vascular cognitive impairment or vascular dementia. In this article, the roles of functional brain imaging are discussed in evaluation of subcortical lesions disrupting cortico-subcortical circuits and in the study of white-matter changes in dementia. Also mentioned is an ongoing clinical trial of extracranial-intracranial artery bypass surgery for hemispheric hemodynamic misery perfusion where single-photon emission tomography is used as a surrogate measure.","Aged;Biomarkers;Brain/ blood supply/ metabolism;Cognition Disorders/ diagnosis/ etiology;Dementia, Vascular/complications/diagnosis/physiopathology;Humans;Positron-Emission Tomography;Severity of Illness Index;Tomography, Emission-Computed, Single-Photon","Mori, E.",2003,,10.1017/s1041610203009311,0,
2385,Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer's disease: a voxel-based lesion mapping study,"INTRODUCTION: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD. METHODS: WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE epsilon4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network. RESULTS: WM hyperintensity volume was significantly greater in non-carriers of the APOE epsilon4 allele. Lesion distribution was similar among epsilon4 carriers and non-carriers. Only epsilon4 non-carriers showed a correlation between lesion volume and cognitive performance. CONCLUSION: The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE epsilon4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE epsilon4-mediated risk.",,"Morgen, K.;Schneider, M.;Frolich, L.;Tost, H.;Plichta, M. M.;Kolsch, H.;Rakebrandt, F.;Rienhoff, O.;Jessen, F.;Peters, O.;Jahn, H.;Luckhaus, C.;Hull, M.;Gertz, H. J.;Schroder, J.;Hampel, H.;Teipel, S. J.;Pantel, J.;Heuser, I.;Wiltfang, J.;Ruther, E.;Kornhuber, J.;Maier, W.;Meyer-Lindenberg, A.",2015,,10.1186/s13195-015-0111-8,0,
2386,"Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events. A controlled, open-label study","Behavioral problems produce excess disability, potentially devastating in cognitively impaired patients. These behavioral symptoms can be a major cause of stress, anxiety and concern for caregivers. While psychotropic drugs are frequently used to control these symptoms, they have the potential for significant side effects, which include sedation, disinhibition, depression, falls, incontinence, parkinsonism and akathisia. We followed up (for 12 months) a group of 346 consecutive outpatients, with a diagnosis of subcortical vascular dementia or multi-infarctual dementia. Patients eligible for this open-label study were required to have behavioral problems (BPSD). Patients were divided into two groups, Group A received olanzapine 2.5-7.5 mg/day while Group B received typical antipsychotics. Patients in both groups were allowed to continue any previous therapy. Patients in both groups were significantly improved in their BPSD. Our patients had a host of medical conditions and received numerous concomitant medications. Given the potential complications associated with these therapeutic agents, these patients tolerated olanzapine quite well. On examination of consequences of adverse events, particularly somnolence, postural instability, and postural hypotension, it appeared that cerebrovascular events were not present. Moreover, no anticholinergic effect was recorded. These findings suggest that olanzapine could be a safe and effective treatment even for elderly population in suitable doses and receiving the adequate follow-up.","Aged;Aged, 80 and over;Antipsychotic Agents/therapeutic use;Behavioral Symptoms/diagnosis/*psychology;Benzodiazepines/therapeutic use;Dementia, Vascular/diagnosis/*psychology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;*Randomized Controlled Trials as Topic;Risk Factors;Serotonin Uptake Inhibitors/*therapeutic use;Stroke/*complications;Time Factors;Tomography, X-Ray Computed;Treatment Outcome","Moretti, R.;Torre, P.;Antonello, R. M.;Cattaruzza, T.;Cazzato, G.",2005,Oct,10.1007/s00415-005-0830-z,0,
2387,Corpus callosum atrophy is associated with gait disorders in patients with leukoaraiosis,"Cognitive impairment and gait disturbances are the most frequent clinical findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has been associated with dementia in patients with LA, as well as with gait disturbances in patients with normal pressure hydrocephalus. We investigated, in patients with LA, the possible association between gait impairment and CC atrophy, taking into account cognitive deficits and the other brain lesions commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5±6.3 years) with gait disturbances and brain CT images consistent with LA underwent an assessment of gait and a cognitive assessment of global and selective functions. Magnetic resonance imaging (MRI) was used to measure thickness and area of the CC, total LA volume, lacunar infarcts and size of lateral ventricles. We examined the effect of every MRI change on each performance measure. Reduction of CC thickness, particularly that of the anterior segment, had a significant effect on severity of gait impairment, as measured using the gait scale's score. It was independent of any other brain changes revealed by MRI, including LA. An independent, significant association was also found between CC area and the Left Hand Praxis test results. In patients with LA, CC atrophy is associated with gait impairment independently of LA and other brain abnormalities usually present in these patients. © Springer-Verlag Italia 2005.",,"Moretti, M.;Carlucci, G.;Di Carlo, A.;Fonda, C.;Prieto, M.;Mugnai, S.;Bracco, L.;Piccini, C.;Pracucci, G.;Inzitari, D.",2005,June,,0,
2388,Vascular damage and EEG markers in subjects with mild cognitive impairment,"OBJECTIVE: We evaluated the changes induced by cerebrovascular (CV) damage on brain rhythmicity recorded by electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). METHODS: We enrolled 99 MCI subjects (Mini-Mental State Examination [MMSE] mean score 26.6). All subjects underwent EEG recording and magnetic resonance imaging (MRI). EEGs were recorded at rest. Individual EEG frequencies were indexed by the theta/alpha transition frequency (TF) and by the individual alpha frequency (IAF) with power peak in the extended alpha range (5-14 Hz). Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands on the basis of the TF and IAF values. Subsequently, we divided the cohort in four sub-groups based on subcortical CV damage as scored by the age-related white matter changes scale (ARWMC). RESULTS: CV damage was associated with 'slowing' of TF proportional to its severity. In the spectral bandpower the severity of vascular damage was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with IAF and alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. CONCLUSIONS: EEG analysis may show physiological markers sensitive to CV damage. The appropriate use of this EEG index may help the differential diagnosis of different forms of cognitive decline, namely primary degenerative and secondary to CV damage. SIGNIFICANCE: The EEG neurophysiological approach, together with anatomical features from imaging, could be helpful in the understanding of the functional substrate of dementing disorders.",Aged;Alpha Rhythm;Brain/ physiopathology;Cerebrovascular Disorders/ complications/diagnosis;Cognition Disorders/ complications/diagnosis/ physiopathology;Cohort Studies;Delta Rhythm;Electroencephalography;Female;Humans;Magnetic Resonance Imaging;Male;Severity of Illness Index;Theta Rhythm,"Moretti, D. V.;Miniussi, C.;Frisoni, G.;Zanetti, O.;Binetti, G.;Geroldi, C.;Galluzzi, S.;Rossini, P. M.",2007,Aug,10.1016/j.clinph.2007.05.009,0,
2389,Cerebral hyperperfusion on arterial spin labeling MRI during CADASIL migrainous encephalopathy,"Migrainous encephalopathy is a rare and poorly understood manifestation of the inherited vasculopathy cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Patients may present with migraine with aura, complicated by confusion, fever, and decreased conscious level. 1 In this case, a patient with migrainous encephalopathy underwent cerebral perfusion imaging with arterial spin labeling (ASL) MRI before, during, and following admission.",,"Moreton, F. C.;Santosh, C.;McArthur, K.;Muir, K. W.",2015,15,,0,
2390,Changing clinical patterns and increasing prevalence in CADASIL,"Objectives: CADASIL is a monogenic small vessel vasculopathy causing recurrent stroke. Early descriptions suggested dementia and disability were common from the 5th decade but there is evidence of marked phenotypic variability. We investigated the prevalence and clinical features of CADASIL in the west of Scotland. Methods: We undertook a retrospective review of clinical records of patients with confirmed CADASIL identified through a specialist clinic. Patients were divided to examine the effect of date of diagnosis on clinical outcomes and the characteristics at different ages. The location of pedigree members was used to estimate prevalence. Results: Twenty-one different CADASIL-causing NOTCH3 mutations were identified in 49 pedigrees (61% in exon 4). Disease prevalence in Glasgow was 4.6/100,000 adults. Mutation prevalence was estimated at 10.7/100,000 population. Median age at first stroke in women (57 years) was higher than previous estimates, and stroke age in men was higher in patients diagnosed more recently (pre 2006 46 years, post 2006 56 years, P = 0.034). In patients over 58 years of age, 13/34 (38%) were living independently and 17/28 (61%) were mobile without aids when last seen. Conclusions: CADASIL prevalence is at least 4.6 per 100,000 adults. Median age of first stroke may be older than previously thought. Clinicians should consider CADASIL in the differential diagnosis even in older patients with stroke. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",antihypertensive agent;antithrombocytic agent;cysteine;hydroxymethylglutaryl coenzyme A reductase inhibitor;Notch3 receptor;osmium;adult;article;CADASIL;cerebrovascular accident;clinical feature;cognitive defect;depression;ethnicity;exon;female;gait disorder;gene mutation;Glasgow coma scale;hospital;human;human tissue;hypercholesterolemia;hypertension;latent period;major clinical study;male;medical record;middle aged;migraine;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;nursing home patient;outcome assessment;pedigree;prevalence;psychosis;retrospective study;risk factor;seizure;skin biopsy;smoking;transient ischemic attack;United Kingdom;Signa,"Moreton, F. C.;Razvi, S. S. M.;Davidson, R.;Muir, K. W.",2014,,,0,
2391,Arterial branching and basal ganglia lacunes: A study in pure small vessel disease,"Introduction: Lacunes are defined morphologically by size and location, but radiological characteristics alone may be unable to distinguish small vessel disease aetiology from alternative mechanisms. We investigated the branching order of arterial vessels associated with basal ganglia lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in order to improve the understanding of their pathogenesis in pure cerebral small vessel disease. Patients and methods: Adults with a confirmed diagnosis of CADASIL were included. A pilot study was conducted in a Scottish CADASIL cohort. The Paris–Munich CADASIL cohort was used for independent validation. Lacunes identified on T1-weighted magnetic resonance imaging scans were registered to a standard brain template. A microangiographic template of the basal ganglia vasculature was automatically overlaid onto coronal slices, and raters estimated the vessel branching order related to each lacune. Results: Of 179 lacunes, 150 (84%) were associated with third-order vessels. In 14 incident lacunes, 11 (79%) were associated with third-order vessels. In the pilot study, lacune volume was significantly lower in lacunes associated with third-order vessels (0.04 ml ± 0.04 ml) compared to second-order vessels (0.48 ± 0.16 ml; p < 0.001). Discussion: In this study of CADASIL patients, most lacunes were small and associated with third-order vessel disease. This suggests that these are the vessels primarily affected in cerebral small vessel disease. Microangiographic template techniques could be used to further investigate in a general stroke population whether finding large lacunes originating from higher order vessels indicates an alternative cause of stroke. Conclusion: Lacunes in pure small vessel disease are associated with the smallest vessels in the basal ganglia.",adult;aged;arterial branching;article;basal ganglia lacune;basal ganglion;blood vessel parameters;brain blood vessel;brain infarction;brain infarction size;CADASIL;cerebrovascular disease;clinical article;female;human;male;microangiography;nuclear magnetic resonance imaging;pilot study;priority journal;risk factor,"Moreton, F. C.;Düring, M.;Phan, T.;Srikanth, V.;Beare, R.;Huang, X.;Jouvent, E.;Chabriat, H.;Dichgans, M.;Muir, K. W.",2017,,10.1177/2396987317718450,0,
2392,Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults,"Introduction Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. Material and methods Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. Results We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) Conclusions DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.",aged;Alzheimer disease;article;brain infarction;cerebrovascular disease;cross-sectional study;dementia;depression;diabetes mellitus;disease association;dyslipidemia;human;hypertension;major clinical study;Mexican;neuroimaging;risk factor;white matter lesion,"Moreno Cervantes, C.;Mimenza Alvarado, A.;Aguilar Navarro, S.;Alvarado Ávila, P.;Gutiérrez Gutiérrez, L.;Juárez Arellano, S.;Ávila Funes, J. A.",2017,,10.1016/j.nrl.2015.12.006,0,
2393,,"Introduction: Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. Material and methods: Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. Results: We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004). Conclusions: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.",aged;Alzheimer disease;controlled study;cross-sectional study;diabetes mellitus;diagnosis;dyslipidemia;human;hypertension;imaging;lacunar stroke;major clinical study;memory;Mexico;multivariate analysis;risk factor;tertiary care center;white matter,"Moreno Cervantes, C.;Mimenza Alvarado, A.;Aguilar Navarro, S.;Alvarado Ávila, P.;Gutiérrez Gutiérrez, L.;Juárez Arellano, S.;Ávila Funes, J. A.",2016,,,0,
2394,Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults Factores asociados a la demencia mixta en comparacion con demencia tipo Alzheimer en adultos mayores mexicanos,"INTRODUCTION: Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. MATERIAL AND METHODS: Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. RESULTS: We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.",Alzheimer disease;Demencia mixta;Depresion;Depression;Diabetes;Enfermedad de Alzheimer;Hipertension;Hypertension;Mixed dementia,"Moreno Cervantes, C.;Mimenza Alvarado, A.;Aguilar Navarro, S.;Alvarado Avila, P.;Gutierrez Gutierrez, L.;Juarez Arellano, S.;Avila Funes, J. A.",2016,Mar 09,,0,
2395,Factors associated with mixed dementia vs Alzheimer disease in elderly Mexican adults,"INTRODUCTION: Mixed dementia (DMix) refers to dementia resulting from Alzheimer disease in addition to cerebrovascular disease. The study objectives were to determine the clinical and imaging factors associated with Dmix and compare them to those associated with Alzheimer disease. MATERIAL AND METHODS: Cross-sectional study including 225 subjects aged 65 years and over from a memory clinic in a tertiary hospital in Mexico City. All patients underwent clinical, neuropsychological, and brain imaging studies. We included patients diagnosed with DMix or Alzheimer disease (AD). A multivariate analysis was used to determine factors associated with DMix. RESULTS: We studied 137 subjects diagnosed with Dmix. Compared to patients with AD, Dmix patients were older and more likely to present diabetes, hypertension, dyslipidaemia, and history of cerebrovascular disease (P<.05). The multivariate analysis showed that hypertension (OR 1.92, CI 1.62-28.82; P=.009), white matter disease (OR 3.61, CI 8.55-159.80; P<.001), and lacunar infarcts (OR 3.35, CI 1.97-412.34; P=.014) were associated with Dmix, whereas a history of successfully treated depression showed an inverse association (OR 0.11, CI 0.02-0-47; P=.004) CONCLUSIONS: DMix may be more frequent than AD. Risk factors such as advanced age and other potentially modifiable factors were associated with this type of dementia. Clinicians should understand and be able to define Dmix.",,"Moreno Cervantes, C.;Mimenza Alvarado, A.;Aguilar Navarro, S.;Alvarado Avila, P.;Gutierrez Gutierrez, L.;Juarez Arellano, S.;Avila Funes, J. A.",2016,Mar 9,10.1016/j.nrl.2015.12.006,0,
2396,Brain atrophy in type 2 diabetes: regional distribution and influence on cognition,"OBJECTIVE: Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function. RESEARCH DESIGN AND METHODS: This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures. RESULTS: T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P </= 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume. CONCLUSIONS: Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.","Aged;Atrophy/etiology/pathology/physiopathology;Brain/ pathology/physiopathology;Cerebrovascular Disorders/diagnosis/ etiology/physiopathology;Cognition/ physiology;Cross-Sectional Studies;Diabetes Mellitus, Type 2/ complications;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Retrospective Studies;Risk Factors","Moran, C.;Phan, T. G.;Chen, J.;Blizzard, L.;Beare, R.;Venn, A.;Munch, G.;Wood, A. G.;Forbes, J.;Greenaway, T. M.;Pearson, S.;Srikanth, V.",2013,Dec,10.2337/dc13-0143,0,
2397,Predicting dementia development in Parkinson's disease using Bayesian network classifiers,"Parkinson's disease (PD) has broadly been associated with mild cognitive impairment (PDMCI) and dementia (PDD). Researchers have studied surrogate, neuroanatomic biomarkers provided by magnetic resonance imaging (MRI) that may help in the early diagnosis of this condition. In this article, four classification models (naive Bayes, multivariate filter-based naive Bayes, filter selective naive Bayes and support vector machines, SVM) have been applied to evaluate their capacity to discriminate between cognitively intact patients with Parkinson's disease (PDCI), PDMCI and PDD. For this purpose, the MRI studies of 45 subjects (16 PDCI, 15 PDMCI and 14 PDD) were acquired and post-processed with Freesurfer, obtaining 112 variables (volumes of subcortical structures and thickness of cortical parcels) per subject. A multivariate filter-based naive Bayes model was found to be the best classifier, having the highest cross-validated sensitivity, specificity and accuracy. Additionally, the most relevant variables related to dementia in PD, as predicted by our classifiers, were cerebral white matter, and volumes of the lateral ventricles and hippocampi.","Aged;Bayes Theorem;Brain/pathology;Dementia/ complications/ diagnosis/pathology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ complications/ diagnosis/pathology;Neuroimaging;Parkinson Disease/ complications/pathology;Predictive Value of Tests;Sensitivity and Specificity;Support Vector Machine","Morales, D. A.;Vives-Gilabert, Y.;Gomez-Anson, B.;Bengoetxea, E.;Larranaga, P.;Bielza, C.;Pagonabarraga, J.;Kulisevsky, J.;Corcuera-Solano, I.;Delfino, M.",2013,Aug 30,10.1016/j.pscychresns.2012.06.001,0,
2398,The application of DTI to investigate abnormalities in schizophrenia and alzheimer disease,"The objective of this study was to evaluate in individuals applications at clinical high risk of mental disorder with Diffusion Tensor Imaging (DTI-MRI). This provides an important opportunity for pathological mechanisms of Schizophrenia Disease (SD) and Alzheimer Disease (AD), related to mental disorder. All disease is associated with abnormal activity distributed spatially in neural systems with mediate the motor and cognitive manifestations of this disorder in combination with processing and visualization techniques for Diffusion Tensor Magnetic Resonance Imaging (DTI-MRI). It is possible that metabolic MRI studies have demonstrated that this illness is characterized by a set of reproducible functional brain networks that correlate with these clinical features. The time at which these abnormalities appear is unknown, as is their relationship to concurrent clinical and indices of disease progression. We therefore need to set vivo biomarkers that can distinguish the differing pathologies and their contribution to the clinical features of the conditions. Diffusion tensor imaging (DTI) utilizes the anisotropic nature of diffusion in neuronal white matter tracts. With neuronal degeneration, the mean diffusivity (MD) increases with the loss of structural barriers that restrict normal diffusion, and diffusion becomes less directionally oriented, which is associated with a reduction in fractional anisotropy (FA). Areas of reduced FA in subjects with lateral ventricle were found primarily in occipital parietal area with white matter tracts; in AD, it was also associated with reduced FA in the points the left thalamus.",Alzheimer disease;amygdala;article;basal ganglion;brain lateral ventricle;brain size;cerebellum;clinical feature;cognitive defect;corpus callosum;diffusion tensor imaging;fractional anisotropy;functional brain network;high risk population;hippocampus;human;image processing;mean diffusivity;motor dysfunction;nerve cell degeneration;nerve cell network;nerve tract;neuroimaging;neuropathology;occipital cortex;parahippocampal gyrus;parietal lobe;radiological parameters;schizophrenia;superior temporal gyrus;supramarginal gyrus;thalamus;white matter;white matter fiber tract,"Mora, M. L.;Hurtado, C. A.;Prchkovska, V.;Rodrigues, P.;López Ibor, J. J.;Arrazola, J.",2015,,,0,2399
2399,The application of DTI to investigate abnormalities in schizophrenia and alzheimer disease,"The objective of this study was to evaluate in individuals applications at clinical high risk of mental disorder with Diffusion Tensor Imaging (DTI-MRI). This provides an important opportunity for pathological mechanisms of Schizophrenia Disease (SD) and Alzheimer Disease (AD), related to mental disorder. All disease is associated with abnormal activity distributed spatially in neural systems with mediate the motor and cognitive manifestations of this disorder in combination with processing and visualization techniques for Diffusion Tensor Magnetic Resonance Imaging (DTI-MRI). It is possible that metabolic MRI studies have demonstrated that this illness is characterized by a set of reproducible functional brain networks that correlate with these clinical features. The time at which these abnormalities appear is unknown, as is their relationship to concurrent clinical and indices of disease progression. We therefore need to set vivo biomarkers that can distinguish the differing pathologies and their contribution to the clinical features of the conditions. Diffusion tensor imaging (DTI) utilizes the anisotropic nature of diffusion in neuronal white matter tracts. With neuronal degeneration, the mean diffusivity (MD) increases with the loss of structural barriers that restrict normal diffusion, and diffusion becomes less directionally oriented, which is associated with a reduction in fractional anisotropy (FA). Areas of reduced",,"Mora, M. L.;Hurtado, C. A.;Prchkovska, V.;Rodrigues, P.;López Ibor, J. J.;Arrazola, J.",,2015,,0,
2400,Vitamin D deficiency disrupts neuronal integrity in cognitively impaired patients,"BACKGROUND: Emerging evidence suggests that low serum 25-hydroxyvitamin D (25OHD) may induce cognitive decline and dementia, however, the pathophysiological mechanisms are poorly understood. OBJECTIVE: We sought to determine the relationship between vitamin D deficiency and neuronal integrity in cognitively impaired patients. METHODS: One hundred nine patients with memory impairment were divided into quartiles according to serum concentrations of 25OHD concentration, from lowest (L-25OHD) to highest (H-25OHD). The diffusion tensor images from the L-25OHD group and the H-25OHD group were assessed. A mask of regional white matter hyperintensities was obtained in the T1-weighted image space. Data were analyzed using tract-based spatial statistics with a nonlinear registration algorithm. RESULTS: Patients in the L-25OHD group had lower fractional anisotropy values compared with patients in the H-25OHD group in the frontal parts of the inferior and superior longitudinal fasciculi, cingulum bundle, corpus callosum (genu), anterior limb of the internal capsule, and anterior corona radiata (familywise error corrected, p < 0.05). CONCLUSIONS: Vitamin D deficiency is associated with disruption of neuronal integrity, primarily in frontal regions. Vitamin D deficiency may lead to the loss of neuroprotective properties in cerebral ischemia and vascular lesions, contributing to memory impairment.",Aged;Anisotropy;Brain/ pathology;Cognition Disorders/blood/ pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Humans;Male;Severity of Illness Index;Vitamin D/analogs & derivatives/blood;Vitamin D Deficiency/blood/ pathology/psychology;White Matter/pathology,"Moon, Y.;Moon, W. J.;Kwon, H.;Lee, J. M.;Han, S. H.",2015,,10.3233/jad-143063,0,
2401,Vascular factors are associated with the severity of the neuropsychiatric symptoms in Alzheimer's disease,"INTRODUCTION: The purpose of this study is to determine whether vascular risk factors are associated with severity of neuropsychiatric symptoms (NPS) in patients of Alzheimer's dementia. METHODS: We reviewed medical records of 162 patients with Alzheimer's dementia. The NPS were assessed using the Neuropsychiatric Inventory (NPI). Hypertension and cardiovascular events were detected through detailed history taking. Diabetes mellitus and hyperlipidemia were uncovered through laboratory test. The asymptomatic stroke and white matter hyperintensities (WMH) were defined by magnetic resonance imaging. Partial correlation analysis was used. RESULTS: Hypertension was correlated with the severity of apathy (r = 0.231, p = 0.015). The asymptomatic stroke was related to the severity of depression (r = 0.255, p = 0.007). The remaining vascular factors were not significant. CONCLUSION: Presence of hypertension and asymptomatic stroke are related with the severity of apathy and depression in Alzheimer's dementia.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ psychology;Apathy;Depression/ complications/psychology;Female;Humans;Hypertension/ complications;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies;Severity of Illness Index","Moon, Y.;Kim, H.;Ok Kim, J.;Han, S. H.",2014,Jul,10.3109/00207454.2013.856902,0,
2402,Fluid-attenuated inversion recovery hypointensity of the pulvinar nucleus of patients with Alzheimer disease: its possible association with iron accumulation as evidenced by the t2(*) map,"OBJECTIVE: We hypothesized that prominent pulvinar hypointensity in brain MRI represents the disease process due to iron accumulation in Alzheimer disease (AD). We aimed to determine whether or not the pulvinar signal intensity (SI) on the fluid-attenuated inversion recovery (FLAIR) sequences at 3.0T MRI differs between AD patients and normal subjects, and also whether the pulvinar SI is correlated with the T2(*) map, an imaging marker for tissue iron, and a cognitive scale. MATERIALS AND METHODS: Twenty one consecutive patients with AD and 21 age-matched control subjects were prospectively included in this study. The pulvinar SI was assessed on the FLAIR image. We measured the relative SI ratio of the pulvinar to the corpus callosum. The T2(*) values were calculated from the T2(*) relaxometry map. The differences between the two groups were analyzed, by using a Student t test. The correlation between the measurements was assessed by the Pearson's correlation test. RESULTS: As compared to the normal white matter, the FLAIR signal intensity of the pulvinar nucleus was significantly more hypointense in the AD patients than in the control subjects (p < 0.01). The pulvinar T2(*) was shorter in the AD patients than in the control subjects (51.5 +/- 4.95 ms vs. 56.5 +/- 5.49 ms, respectively, p = 0.003). The pulvinar SI ratio was strongly correlated with the pulvinar T2(*) (r = 0.745, p < 0.001). When controlling for age, only the pulvinar-to-CC SI ratio was positively correlated with that of the Mini-Mental State Examination (MMSE) score (r = 0.303, p < 0.050). Conversely, the pulvinar T2(*) was not correlated with the MMSE score (r = 0.277, p = 0.080). CONCLUSION: The FLAIR hypointensity of the pulvinar nucleus represents an abnormal iron accumulation in AD and may be used as an adjunctive finding for evaluating AD.",Aged;Alzheimer Disease/ metabolism/ pathology;Female;Humans;Iron/ metabolism;Magnetic Resonance Imaging;Male;Pulvinar/metabolism/ pathology,"Moon, W. J.;Kim, H. J.;Roh, H. G.;Choi, J. W.;Han, S. H.",2012,Nov-Dec,10.3348/kjr.2012.13.6.674,0,
2403,Impact of white matter changes on activities of daily living in mild to moderate dementia,"The association between white matter changes and activities of daily living (ADL) in a large, well-defined cohort of patients with mild-to-moderate dementia (either Alzheimer's disease or subcortical vascular dementia) were investigated. A total of 289 patients were divided into three groups (140 mild, 99 moderate, and 50 severe) depending on the degree of white matter changes as indicated on brain magnetic resonance image scans. Further, we analyzed the three groups' performances on basic and instrumental ADL. The degree of white matter changes was associated with greater age, hypertension, previous history of stroke, higher Hachinski Ischemic Score, worse global cognitive and functional status, and an increased impairment of basic ADL and instrumental ADL. The increased impairment with regard to the severe group's performance on both the basic and instrumental ADL remained significant after adjustment for age and hypertension. Tasks involving physical activities were most significant. This was the first study investigating the association between white matter changes and ADL in a large, well-defined dementia cohort. The present study suggests that severe white matter changes may be associated with higher impairment on both basic and instrumental ADL.",Activities of Daily Living/ psychology;Aged;Brain/ pathology/physiopathology;Dementia/ complications/ pathology/physiopathology;Female;Humans;Male;Neuropsychological Tests,"Moon, S. Y.;Na, D. L.;Seo, S. W.;Lee, J. Y.;Ku, B. D.;Kim, S. Y.;Park, K. W.;Shim, Y. S.;Youn, Y. C.;Chung, C. S.;Cheong, H. K.;Choi, S. H.;Cha, K. R.;Kim, J. E.;Jeong, J. H.",2011,,10.1159/000318161,0,
2404,A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient,"We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.","cell surface receptor;Notch receptor;NOTCH3 protein, human;oncoprotein;amino acid substitution;article;biopsy;brain;case report;codon;computer assisted emission tomography;female;genetics;human;Korea;middle aged;missense mutation;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;pathology;point mutation;scintiscanning;skin","Moon, S. Y.;Kim, H. Y.;Seok, J. I.;Kwon, J. C.;Ki, C. S.;Kim, J. W.;Suh, Y. L.;Na, D. L.",2003,,,0,
2405,Silent infarcts demonstrated by diffusion-weighted MRI in CADASIL,,adult;article;autosomal disorder;brain infarction;CADASIL;case report;clinical feature;controlled study;diagnostic imaging;diffusion weighted imaging;disease course;female;human;human cell;human tissue;laboratory test;physical examination;priority journal,"Moon, S. Y.;Ki, C. S.;Kim, J. W.;Suh, Y. L.;Kwon, J. C.;Na, D. L.",2003,,,0,
2406,Associations between white matter hyperintensities and cognitive decline over three years in non-dementia older adults with memory complaints,"We investigated whether the baseline level and overtime changes of white matter hyperintensities (WMH) would be associated with cognitive decline over three years in non-demented older adults with memory complaints. 109 participants with baseline magnetic resonance imaging (MRI) and follow-up cognitive assessments up to 3-year were included; among them, 82 also had a follow-up MRI assessment over three years. WMH volume was obtained by an automated segmentation algorithm. Baseline WMH volumes and change between baseline and follow-up WMH were related to cognitive scores over time using mixed-effect linear regressions. Secondary stratified analyses according to Clinical Dementia Rating (CDR) status, APOE4 status, and presence of amyloid in the brain were conducted using similar regression models. Change in WMH volume overtime was associated with declines in COWAT (beta=-0.239; 95% CI=-0.381, -0.096, p=0.001). Baseline WMH was not associated to any of the cognitive tests. Secondary analysis found that baseline WMH was associated to declines in TMT-A in APOE4 non-carriers (beta=0.343; 95% CI=0.121, 0.564, p=0.003) and CDR 0 groups (beta=0.307; 95% CI=0.095, 0.519, p=0.005); in CDR 0 group, overtime changes in WMH was associated to declines on both TMT-A (beta=0.698; 95% CI=0.270, 1.126, p=0.002) and TMT-B (beta=2.573; 95% CI=1.200, 3.947, p<0.001). Changes in WMH volume are associated with declines in information processing speed and executive function in non-demented older adults with memory complaints. Overtime changes in WMH volume is probably a better determinant of cognitive function in the elderly than baseline WMH volume.",Cognition;Longitudinal;White matter hyperintensities,"Moon, S. Y.;de Souto Barreto, P.;Chupin, M.;Mangin, J. F.;Bouyahia, A.;Fillon, L.;Andrieu, S.;Vellas, B.;group, Mapt Dsa",2017,Aug 15,,0,
2407,Association between Red Blood Cells Omega-3 Polyunsaturated Fatty Acids and White Matter Hyperintensities: The MAPT Study,"OBJECTIVES: The association between circulating biomarkers of red blood cells (RBC) omega-3 polyunsaturated fatty acids (PUFAs) and cerebral white matter hyperintensities (WMH) on the brain MRI remains yet unclear. We investigated the cross-sectional and prospective associations of RBC omega-3 PUFAs with WMH in dementia-free older adults with subjective memory complaints. DESIGN: Participants were 234 older adults with assessments for both PUFA and MRI near to baseline; among them, 79 also had an MRI assessment at 3-year follow-up. The measurement of WMH volume was obtained by an automated segmentation algorithm. We related individual or combinational baseline RBC omega-3 PUFAs levels with baseline WMH volumes and WMH evolution over 3 years. We carried out multiple (cross-sectional) and mixed-effect (prospective analysis, with random effects at participant's level) linear regressions with adjustment for age, sex, time interval between date of blood draw for measurement of fatty acids and date of brain MRI, the status of APOE e4 carrier, body mass index, and vascular risk factors. Associations were considered significant at p </= 0.006 to take into account multiplicity (8 comparisons). RESULTS: None of the eight RBC omega-3 PUFAs tested was significantly associated with WMH at both cross-sectional and prospective analyses. CONCLUSIONS: We did not find any association between omega-3 PUFAs and WMH in non-demented older adults with memory complaints. A longer longitudinal study with data on omega-3 PUFAs and WMH would contribute important information to this field.",Omega-3 polyunsaturated fatty acids;longitudinal;white matter hyperintensities,"Moon, S. Y.;de Souto Barreto, P.;Chupin, M.;Mangin, J. F.;Bouyahia, A.;Fillon, L.;Andrieu, S.;Vellas, B.",2018,,,0,
2408,Physical activity and changes in white matter hyperintensities over three years,"Objectives: Since physical activity (PA) has demonstrated benefits for cardiovascular health, it is possible to hypothesize that higher or increasing PA slows the progression of white matter hyperintensities (WMH). We investigated the association between PA and the progression of WMH in non-demented older adults with memory complaints. Design: We included 152 participants (mean age 74.7±3.8 years; 63.8% women) in the analyses, in whom information on self-reported PA and MRI was available at both baseline and 3-year follow-up. From the PA questionnaire, the baseline metabolic equivalent of task (MET-minute/week) and changes in MET-minute/week over three years were separately calculated for overall, leisure-time, and non-leisure time PA. WMH volume at baseline and 3-year follow-up was obtained by using an automated segmentation algorithm. Results: Mixed-effect linear regression models showed that none of the baseline PA variables was associated with progression of WMH over time. People who had decreased their PA levels over three years tended to show greater progression of WMH compared with those who had maintained PA levels of ≥1200 MET-min/week (roughly equivalent to ≥300 minutes of brisk walking) in the unadjusted model (β±SE=4.85±2.42, p=0.045); however, this association was no longer significant after adjustment for confounders (β±SE =3.63±2.18, p=0.096). Conclusions: We did not find any significant association between PA and WMH in non-demented older adults with memory complaints. However, decrease over time in PA levels tended to be associated with progression of WMH. A larger longitudinal study with data on PA assessed using objective measures would provide important information in this field.",adult;aged;female;follow up;human;linear regression analysis;longitudinal study;major clinical study;male;memory;metabolic equivalent;model;nuclear magnetic resonance imaging;questionnaire;walking;white matter,"Moon, S. Y.;de Souto Barreto, P.;Cesari, M.;Chupin, M.;Mangin, J. F.;Bouyahia, A.;Fillon, L.;Andrieu, S.;Vellas, B.",2017,,10.1007/s12603-017-0959-3,0,
2409,Alterations in white matter volume and its correlation with neuropsychological scales in patients with Alzheimer's disease: a DARTEL-based voxel-based morphometry study,"Background Non-invasive imaging markers can be used to diagnose Alzheimer's disease (AD) in its early stages, but an optimized quantification analysis to measure the brain integrity has been less studied. Purpose To evaluate white matter volume change and its correlation with neuropsychological scales in patients with AD using a diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry (VBM). Material and Methods The 21 participants comprised 11 patients with AD and 10 age-matched healthy controls. High-resolution magnetic resonance imaging (MRI) data were processed by VBM analysis based on DARTEL algorithm. Results The patients showed significant white matter volume reductions in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and parahippocampal gyrus compared to healthy controls. In correlation analysis, the parahippocampal volume was positively correlated with the Korean-mini mental state examination score in AD. Conclusion This study provides an evidence for localized white matter volume deficits in conjunction with cognitive dysfunction in AD. These findings would be helpful to understand the neuroanatomical mechanisms in AD and to robust the diagnostic accuracy for AD.",Aged;Algorithms;Alzheimer Disease/ diagnostic imaging/ pathology;Brain/diagnostic imaging/pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Neuropsychological Tests/ statistics & numerical data;White Matter/ diagnostic imaging/ pathology;Alzheimer's disease (AD);cognitive function;diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL);voxel-based morphometry (VBM);white matter,"Moon, C. M.;Shin, I. S.;Jeong, G. W.",2017,Feb,,0,2410
2410,Alterations in white matter volume and its correlation with neuropsychological scales in patients with Alzheimer's disease: a DARTEL-based voxel-based morphometry study,"BACKGROUND: Non-invasive imaging markers can be used to diagnose Alzheimer's disease (AD) in its early stages, but an optimized quantification analysis to measure the brain integrity has been less studied. PURPOSE: To evaluate white matter volume change and its correlation with neuropsychological scales in patients with AD using a diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry (VBM). MATERIAL AND METHODS: The 21 participants comprised 11 patients with AD and 10 age-matched healthy controls. High-resolution magnetic resonance imaging (MRI) data were processed by VBM analysis based on DARTEL algorithm. RESULTS: The patients showed significant white matter volume reductions in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and parahippocampal gyrus compared to healthy controls. In correlation analysis, the parahippocampal volume was positively correlated with the Korean-mini mental state examination score in AD. CONCLUSION: This study provides an evidence for localized white matter volume deficits in conjunction with cognitive dysfunction in AD. These findings would be helpful to understand the neuroanatomical mechanisms in AD and to robust the diagnostic accuracy for AD.",,"Moon, C. M.;Shin, I. S.;Jeong, G. W.",2016,Apr 13,10.1177/0284185116640162,0,
2411,Effects of donepezil on brain morphometric and metabolic changes in patients with Alzheimer's disease: A DARTEL-based VBM and 1H-MRS,"A few studies have performed on the brain morphometric changes over the whole brain structure following donepezil treatment in patients with Alzheimer's disease (AD). We evaluated the gray matter (GM) and white matter (WM) volume alterations and cellular metabolic changes in patients with AD before and after donepezil treatment, and further to reveal the correlations of the scores of various neuropsychological scales with the volumetric and metabolic changes. Twenty-one subjects comprising of 11 patients with AD and 10 age-matched healthy controls participated in this study. All of the patients participated in the follow-up study 24 weeks following donepezil treatment. In this study, a combination of voxel-based morphometry (VBM) and proton magnetic resonance spectroscopy (1H-MRS) was used to assess the brain morphometric and metabolic alterations in AD. In the GM volumetric analysis, both of the untreated and treated patients with donepezil showed significantly reduced volumes in the hippocampus (Hip), parahippocampal gyrus (PHG), precuneus (PCu) and middle frontal gyrus compared with healthy controls. However, donepezil-treated patients showed significantly increased volumes in the Hip, PCu, fusiform gyrus and caudate nucleus compared to untreated patients. In the WM volumetric analysis, untreated and treated patients showed significant volume reductions in the posterior limb of internal capsule (PLIC), cerebral peduncle of the midbrain and PHG compared to healthy controls. However, there was no significant WM morphological change after donepezil treatment in patients with AD. In MRS study, untreated patients with AD showed decreased N-acetylaspartate/creatine (NAA/Cr) and increased myo-inositol (mI)/Cr compared to healthy controls, while treated patients showed only decreased NAA/Cr in the same comparison. However, the treated patients showed simultaneously increased NAA/Cr and decreased mI/Cr and choline (Cho)/Cr ratios compared to untreated patients. This study shows the regional GM and WM volume changes in combination with metabolic changes following donepezil treatment in AD. These findings would be helpful to aid our understanding of the neuroanatomical mechanisms associated with effects of donepezil on the cognitive function in AD.",choline;creatine;donepezil;inositol;n acetylaspartic acid;Alzheimer disease;article;brain level;brain metabolism;brain size;capsula interna;caudate nucleus;drug effect;follow up;fusiform gyrus;gray matter;middle frontal gyrus;neuroimaging;parahippocampal gyrus;precuneus;priority journal;proton nuclear magnetic resonance;scoring system;treatment outcome;voxel based morphometry;white matter;aricept,"Moon, C. M.;Kim, B. C.;Jeong, G. W.",2016,,,0,
2412,"Migraine, white matter hyperintensities, and subclinical brain infarction in a diverse community: The northern manhattan study","Background and Purpose: Migraine with aura is a risk factor for ischemic stroke. The goals of this study are to examine the association between migraine and subclinical cerebrovascular damage in a race/ethnically diverse older population-based cohort study. METHODS-: In the Northern Manhattan Study (NOMAS), we quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with self-reported migraine, confirmed by the International Classification of Headache Disorders-2 criteria. RESULTS-: Of 546 study participants with imaging and migraine data (41% men; mean age at MRI, 71±8 years; mostly Hispanic [65%]), those reporting migraine overall had double the odds of subclinical brain infarction (adjusted odds ratio, 2.1; 95% confidence interval, 1.0-4.2) when compared with those reporting no migraine, after adjusting for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. CONCLUSIONS-: Migraine may be a risk factor for subclinical brain infarction. Prospective studies are needed in race/ethnically diverse populations. © 2014 American Heart Association, Inc.",,"Monteith, T.;Gardener, H.;Rundek, T.;Dong, C.;Yoshita, M.;Elkind, M. S. V.;Decarli, C.;Sacco, R. L.;Wright, C. B.",2014,June,,0,
2413,Myocerebrohepatopathy spectrum disorder due to POLG mutations: A clinicopathological report,"We report on the clinical, neuropathological, and genetic findings of a Japanese case with myocerebrohepatopathy spectrum (MCHS) disorder due to polymerase gamma (. POLG) mutations. A girl manifested poor sucking and failure to thrive since 4. months of age and had frequent vomiting and developmental regression at 5. months of age. She showed significant hypotonia and hepatomegaly. Laboratory tests showed hepatocellular dysfunction and elevated protein and lactate levels in the cerebrospinal fluid. Her liver function and neurologic condition exacerbated, and she died at 8. months of age. At autopsy, fatty degeneration and fibrosis were observed in the liver. Neuropathological examination revealed white matter-predominant spongy changes with Alzheimer type II glia and loss of myelin. Enzyme activities of the respiratory chain complex I, III, and IV relative to citrate synthase in the muscle were normal in the biopsied muscle tissue, but they were reduced in the liver to 0%, 10%, and 14% of normal values, respectively. In the liver, the copy number of mitochondrial DNA compared to nuclear DNA was reduced to 3.3% of normal values as evaluated by quantitative polymerase chain reaction. Genetic analysis revealed compound heterozygous mutations for POLG (I1185T/A957V). This case represents the differential involvement of multiple organs and phenotype-specific distribution of brain lesions in mitochondrial DNA depletion disorders.",alanine aminotransferase;aspartate aminotransferase;bile acid;bilirubin;cell nucleus DNA;cholinesterase;citrate synthase;cystic fibrosis transmembrane conductance regulator;cytochrome c oxidase;cytosol aminopeptidase;DNA directed DNA polymerase gamma;gamma glutamyltransferase;glucose;lactic acid;mitochondrial DNA;protein;ubidecarenone;alanine aminotransferase blood level;amino acid sequence;article;aspartate aminotransferase blood level;bile acid blood level;bilirubin blood level;body height;body weight;brain atrophy;brain disease;case report;cerebrospinal fluid analysis;child hospitalization;cholinesterase blood level;computer assisted tomography;copy number variation;developmental disorder;electroencephalogram;enteric feeding;evoked auditory response;failure to thrive;female;follow up;gamma glutamyl transferase blood level;gene mutation;gestational age;glucose blood level;head circumference;hepatomegaly;heterozygosity;human;infant;laboratory test;lactate blood level;lethargy;liver disease;liver failure;motor nerve conduction;multiple organ failure;muscle biopsy;muscle hypotonia;muscle weakness;myocerebrohepatopathy spectrum disorder;myoclonus epilepsy;myopathy;nuclear magnetic resonance imaging;protein cerebrospinal fluid level;sensory nerve conduction;sucking;tendon reflex;vitamin supplementation;vomiting;weight gain,"Montassir, H.;Maegaki, Y.;Murayama, K.;Yamazaki, T.;Kohda, M.;Ohtake, A.;Iwasa, H.;Yatsuka, Y.;Okazaki, Y.;Sugiura, C.;Nagata, I.;Toyoshima, M.;Saito, Y.;Itoh, M.;Nishino, I.;Ohno, K.",2015,,,0,
2414,"ApoA1, ApoJ and ApoE Plasma Levels and Genotype Frequencies in Cerebral Amyloid Angiopathy","The involvement of apolipoproteins, such as the ApoE4 isoform, in Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) highlights the fact that certain lipid carriers may participate in soluble beta-amyloid (Abeta) transport. Our general aim was to characterize the soluble levels of the apolipoproteins apoE, apoA1 and apoJ/clusterin and their genotype status in patients with CAA. We analyzed the genotypes frequency of APOA1 (rs5069, rs670), CLU (rs11136000, rs1532278, rs7012010, rs9331888) and APOE (rs429358, rs7412) in a cohort of patients with CAA-associated intracerebral hemorrhage (ICH) (n = 59) and compared the results with those from hypertension-associated ICH (n = 42), AD patients (n = 73) and controls (n = 88). In a subgroup of patients, we also determined the plasma concentrations of apoE, apoA1 and apoJ/clusterin. We found increased plasma apoJ/clusterin levels in CAA patients compared to AD patients or controls after adjusting for sex and age (CAA vs. controls, p = 0.033; CAA vs. AD, p = 0.013). ApoA1 levels were not altered between groups, although a strong correlation was observed between plasma Abeta(1-40) and apoA1 among CAA patients (r = 0.583, p = 0.007). Regarding plasma apoE concentration, a robust association between circulating levels and genotype status was confirmed (p < 0.001). Whereas the APOE4 frequency was higher in AD (p < 0.001) and CAA (p = 0.013), the APOA1 and CLU genotypes were not different among groups. In the CAA cohort, the risk-linked CLU variant (C) rs11136000 was associated with white matter hyperintensities (p = 0.045) and the presence of lobar microbleeds (p = 0.023) on MRI. In summary, our findings suggest that apoA1 may act as a physiological transporter of Abeta(1-40) and that apoJ/clusterin appears to be a chaperone related to distinctive lesions in CAA brains.",Apoa1;Apoe;Apoj;Alzheimer's disease;Clu;Cerebral Amyloid Angiopathy;Clusterin,"Montanola, A.;de Retana, S. F.;Lopez-Rueda, A.;Merino-Zamorano, C.;Penalba, A.;Fernandez-Alvarez, P.;Rodriguez-Luna, D.;Malagelada, A.;Pujadas, F.;Montaner, J.;Hernandez-Guillamon, M.",2016,Mar,10.1007/s12017-015-8381-7,0,
2415,Cardiovascular prevention of cognitive decline,"Midlife cardiovascular risk factors, including diabetes, hypertension, dyslipemia, and an unhealthy lifestyle, have been linked to subsequent incidence, delay of onset, and progression rate of Alzheimer disease and vascular dementia. Conversely, optimal treatment of cardiovascular risk factors prevents and slows down age-related cognitive disorders. The impact of antihypertensive therapy on cognitive outcome in patients with hypertension was assessed in large trials which demonstrated a reduction in progression of MRI white matter hyperintensities, in cognitive decline and in incidence of dementia. Large-scale database correlated statin use and reduction in the incidence of dementia, mainly in patients with documented atherosclerosis, but clinical trials failed to reach similar conclusions. Whether a multitargeted intervention would substantially improve protection, quality of life, and reduce medical cost expenditures in patients with lower risk profile has not been ascertained. This would require appropriately designed trials targeting large populations and focusing on cognitive decline as a primary outcome endpoint.",,"Monsuez, J. J.;Gesquiere-Dando, A.;Rivera, S.",2011,,10.4061/2011/250970,0,
2416,Measurement of viral sequences in cerebrospinal fluid of AIDS patients with cerebral white-matter lesions using polymerase chain reaction,"OBJECTIVES: To optimize the use of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for the evaluation of central nervous system (CNS) white-matter lesions that along with clinical findings and magnetic resonance imaging (MRI) can allow a definite diagnosis to be made; also to evaluate treatment with zidovudine plus foscarnet. DESIGN AND METHODS: Fifteen AIDS patients with uncertain CNS white-matter lesions were identified. HIV-1 RNA, cytomegalovirus (CMV) and JC virus (JCV) DNA were measured in a total of 29 CSF samples. The results were correlated with clinical and MRI findings and treatment with zidovudine plus foscarnet was evaluated. RESULTS: Four and five out of 15 patients with CMV DNA > or = 1 : 625 and JCV DNA > or = 10(3) copies/microl detected in the CSF were diagnosed with CMV and progressive multifocal leukoencephalopathy (PML), respectively. Six patients who were CMV/JCV-negative with the highest levels of HIV RNA (median, 6.87 log10 copies/ml) in CSF were considered as having HIV-1 encephalitis. Neurological symptoms were non-supportive for diagnosis as was MRI in 11 out of 15 patients. Nine patients completed a 21-day course of zidovudine plus foscarnet. HIV RNA decreased irrespective of neurological diagnosis. All three HIV-1 encephalitis patients and two out of three patients with CMV leukoencephalopathy improved. In these two latter patients, relief of clinical symptoms coincided with decreased CMV DNA. JCV DNA remained unchanged and all three PML patients deteriorated. CONCLUSIONS: Measurement of CSF viral sequences supports the diagnosis of CNS white-matter lesions in AIDS patients. While effective therapy for PML remains elusive, treatment including zidovudine plus foscarnet may be a promising option for HIV-1 and CMV-related manifestations.","AIDS Dementia Complex/diagnosis/drug therapy/pathology/ virology;AIDS-Related Opportunistic Infections/drug therapy/virology;Adolescent;Adult;Anti-HIV Agents/therapeutic use;Brain/pathology;Cytomegalovirus/ isolation & purification;Cytomegalovirus Infections/diagnosis/drug therapy/virology;DNA, Viral/ cerebrospinal fluid;Drug Therapy, Combination;Female;Foscarnet/therapeutic use;HIV-1/isolation & purification;Humans","Monno, L.;Di Stefano, M.;Zimatore, G. B.;Andreula, C. F.;Appice, A.;Perulli, L. M.;Fiore, J. R.;Pastore, G.;Angarano, G.",1998,Apr 16,,0,
2417,Are transversal MR images sufficient to distinguish persons with mild cognitive impairment from healthy controls?,"RATIONALE AND OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This study aims to determine whether current standard magnetic resonance imaging (MRI) is providing markers that can distinguish between subjects with amnestic MCI (aMCI), nonamnestic MCI (naMCI), and healthy controls (HCs). MATERIALS AND METHODS: A subset of 126 MCI subjects and 126 age-, gender-, and education-appropriate HCs (mean age, 70.9 years) were recruited from 4157 participants in the longitudinal community-based Heinz Nixdorf Recall Study. The burden of white matter hyperintensities (WMHs), cerebral microbleeds, and brain atrophy was evaluated on transversal MR images from a single 1.5-T MR scanner by two blinded neuroradiologists. Logistic regression and receiver-operating characteristic analysis were used for statistical analysis. RESULTS: Occipital WMH burden was significantly increased in aMCI, but not in naMCI relative to HCs (P = .01). The combined MCI group showed brain atrophy relative to HCs (P = .01) pronounced at caudate nuclei (P = .01) and temporal horn level (P = .004) of aMCI patients and increased at the frontal and occipital horns of naMCI patients compared to either aMCI or HCs. Microbleeds were equally distributed in the MCI and control group, but more frequent in aMCI (22 of 84) compared to naMCI subjects (3 of 23). CONCLUSIONS: In his cohort, increased occipital WMHs and cortical and subcortical brain atrophies at temporal horn and caudate nuclei level distinguished aMCI from naMCI subjects and controls. Volumetric indices appear of interest and should be assessed under reproducible conditions to gain diagnostic accuracy.",,"Monninghoff, C.;Dlugaj, M.;Kraff, O.;Geisel, M. H.;Jockel, K. H.;Erbel, R.;Weimar, C.;Wanke, I.",2015,Sep,10.1016/j.acra.2015.04.008,0,
2418,Distinct phenotypic and functional features of CADASIL mutations in the Notch3 ligand binding domain,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant small-vessel disease of the brain caused by mutations in the NOTCH3 receptor. The highly stereotyped nature of the mutations, which alter the number of cysteine residues within the epidermal growth factor-like repeats (EGFR), predicts that all mutations share common mechanisms. Prior in vitro assays and genetic studies in the mouse support the hypothesis that common mutations do not compromise canonical Notch3 function but instead convey a non-physiological and deleterious activity to the receptor through the unpaired cysteine residue. Intriguingly, in vitro studies predict that mutations located in the Delta/Serrate/LAG-2 ligand binding domain-(EGFR10-11) may result in a loss of Notch3 receptor function. However, the in vivo relevance and functional significance of this with respect to the pathogenic mechanisms and clinical expression of the disease remain largely unexplored. To ascertain, in vivo, the functional significance of EGFR10-11 mutations, we generated transgenic mice with one representative mutation (C428S) in EGFR10 of Notch3. These mice, like those with a common R90C mutation, developed characteristic arterial accumulation of Notch3 protein and granular osmiophilic material upon aging. By introducing the mutant C428S transgene into a Notch3 null background, we found that, unlike the R90C mutant protein, the C428S mutant protein has lost wild-type Notch3 activity and exhibited mild dominant-negative activity in three different biological settings. From a large prospectively recruited cohort of 176 CADASIL patients, we identified 10 patients, from five distinct pedigrees carrying a mutation in EGFR10 or 11. These mutations were associated with significantly higher Mini-Mental State Examination and Mattis Dementia Rating Scale scores (P < 0.05), when compared with common mutations. Additionally, we found a strong effect of this genotype on the burden of white matter hyperintensities (P < 0.01). Collectively, these results highlight distinctive functional and phenotypic features of EGFR10-11 mutations relative to the common CADASIL mutations. Our findings are compatible with the hypothesis that EGFR10-11 mutations cause the disease through the same gain of novel function as the common mutations, and lead us to propose that reduced Notch3 signalling acts as a modifier of the CADASIL phenotype.","Adult;Aged;Animals;Brain/pathology;CADASIL/*genetics/metabolism/pathology;Cerebral Arteries/metabolism/ultrastructure;Disease Models, Animal;Genotype;Humans;Ligands;Magnetic Resonance Imaging/methods;Mice;Mice, Transgenic;Microscopy, Electron;Middle Aged;Muscle, Smooth, Vascular/metabolism/ultrastructure;*Mutation;Phenotype;Prospective Studies;Receptors, Notch/*genetics/metabolism/physiology;Reverse Transcriptase Polymerase Chain Reaction/methods","Monet-Lepretre, M.;Bardot, B.;Lemaire, B.;Domenga, V.;Godin, O.;Dichgans, M.;Tournier-Lasserve, E.;Cohen-Tannoudji, M.;Chabriat, H.;Joutel, A.",2009,Jun,10.1093/brain/awp049,0,
2419,A mathematical formula for prediction of gray and white matter volume recovery in abstinent alcohol dependent individuals,"We propose a mathematical formula that predicts the trajectory of the recovery from lobar gray and white matter volume deficits in individuals with sustained abstinence from alcohol. The formula was validated by using MRI-measured volumetric data from 16 alcohol dependent individuals who had brain scans at three time points during abstinence from alcohol. Using the measured volumetric data of each individual from the first two time points, we estimated the individual's gray and white matter volume of the frontal, parietal and temporal lobes for the third time point using the formula. Similarly, using the measured data for the second and third time points, we estimated the first time point data for each individual. The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter. The intra-class correlation coefficients between the measured data and the data estimated from the formula were >. 0.95 for almost all the tissues. The formula may also be applicable in other neuroimaging studies of tissue volume changes such as white matter myelination during brain development and white matter demyelination or brain volume loss in neurodegenerative diseases, such as Alzheimer's disease. © 2011.",adult;aged;alcohol abstinence;alcoholism;article;brain size;clinical article;female;frontal lobe;gray matter;human;human tissue;male;mathematical model;nuclear magnetic resonance imaging;parietal lobe;priority journal;temporal lobe;white matter,"Mon, A.;Delucchi, K.;Durazzo, T. C.;Gazdzinski, S.;Meyerhoff, D. J.",2011,,,0,
2420,Crossed cerebellar diaschisis in cerebrovascular disease detected by N-isopropyl I-123 p-iodoamphetamine (I-123 IMP) with SPECT,"To evaluate the relationship between supratentorial lesion and cerebellar perfusion, twenty-four patients with a variety of cerebrovascular diseases were examined with X-ray CT and I-123 IMP-SPECT. The individual injected dosages were 3 mCi and imaging was performed 20 min after an intravenous injection using the GE 400 A/T or AC/T, a low-energy general purpose collimator, 360° rotation, giving 64 images with an average total imaging time of 32 min. A Ramp filter with additional three dimensional filtering was used for image reconstruction. The presence of cerebellar asymmetry was related to the appearance of the supratentorial lesion. Nine out of thirteen patients with cerebral infarction were observed to have cerebellar asymmetry, even though they showed normal findings of the cerebellum on X-ray CT. This is probably due to the reduced flow in the cerebellar hemisphere contralateral to the supratentorial infarction, 'crossed cerebellar diaschisis'. Three out of five patients with Moyamoya disease and one out of three with an A-V malformation showed cerebellar asymmetry on I-123 IMP-SPECT. In nine normal control subjects, one with multiple infarction with dementia, and one with transient ischemic attack, the cerebellum was symmetrical. Serial studies were also performed in one stroke case and the phenomenon of crossed cerebellar diaschisis disappeared over time. In cerebral infarction with this phenomenon, a large perfusion deficit area in the parietal cortex was characteristic. Our results indicate that this phenomenon might be time dependent and that the mode of onset and the location of the lesion are important in the development of this phenomenon.",,"Momose, T.;Kosaka, N.;Nishikawa, J.",1986,1986,,0,
2421,"Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study","We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97-100% of controls, 81-100% of AD and 67-75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.",Aged;Alzheimer Disease/*pathology;Atrophy;Biomarkers;Cerebral Cortex/pathology;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/*pathology;Gray Matter/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;White Matter/*pathology;Alzheimer's disease;Diagnosis;Discriminant analyses;Frontotemporal dementia;Gray matter atrophy;White matter integrity,"Moller, C.;Hafkemeijer, A.;Pijnenburg, Y. A.;Rombouts, S. A.;van der Grond, J.;Dopper, E.;van Swieten, J.;Versteeg, A.;Pouwels, P. J.;Barkhof, F.;Scheltens, P.;Vrenken, H.;van der Flier, W. M.",2015,,10.1016/j.nicl.2015.08.022,0,
2422,Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: A study with whole brain histogram analysis,"Background and Purpose-In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a large increase in water diffusion has been found both inside and outside the cerebral lesions as detected on conventional MRI. The aim of the present study was to assess the sensitivity of diffusion tensor imaging for monitoring the progression of cerebral tissue damage during the course of CADASIL. Methods-With the use of diffusion tensor imaging, whole brain trace of the diffusion tensor [Trace(D)] histograms were obtained in 22 CADASIL patients and 12 age-matched controls at baseline, in 14 patients after a mean delay of 21 months, and in 5 controls after a mean delay of 29 months. Parameters derived from these histograms (mean value, peak height, and peak location) were analyzed at baseline and during the follow-up. Results-At baseline, all the histogram parameters differed between patients and controls and were found to be significantly correlated with both the Mini-Mental State Examination score and Rankin Scale score in the patient group. The follow-up study showed a decrease in the peak height associated with an increase in the mean value of whole brain Trace(D) histograms in the 14 CADASIL patients scanned twice. The diffusion changes appeared larger in the patients whose Rankin score increased during the study period. Conclusions-These results suggest that the measurement of water diffusion over time is a sensitive marker for the progression of tissue damage in the brain. Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders.",,"Molko, N.;Pappata, S.;Mangin, J. F.;Poupon, F.;LeBihan, D.;Bousser, M. G.;Chabriat, H.",2002,1,,0,
2423,Diffusion tensor imaging study of subcortical gray matter in cadasil,"BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.","Analysis of Variance;Anisotropy;Cerebral Infarction/complications/diagnosis;Dementia, Multi-Infarct/complications/ diagnosis/genetics;Diffusion;Humans;Magnetic Resonance Imaging/ methods;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Proto-Oncogene Proteins/genetics;Putamen/ pathology;Receptors, Cell Surface;Thalamus/ pathology","Molko, N.;Pappata, S.;Mangin, J. F.;Poupon, C.;Vahedi, K.;Jobert, A.;LeBihan, D.;Bousser, M. G.;Chabriat, H.",2001,Sep,,0,
2424,White matter changes in preclinical Alzheimer's disease: A magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels,"The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ(42)+) on the basis of normal cognition and cerebrospinal fluid Aβ(42) levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ(42) levels above 500 pg/mL (CN_Aβ(42)-) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42- in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved.",,"Molinuevo, J. L.;Ripolles, P.;Simó, M.;Lladó, A.;Olives, J.;Balasa, M.;Antonell, A.;Rodriguez-Fornells, A.;Rami, L.",2014,1,,0,
2425,Neuroimaging predictors of cognitive impairment in confluent white matter lesion: Volumetric analyses of 99 brain regions,"Background: Although confluent white matter lesion (WML) is associated with cognitive impairment, the mechanism explaining this association is controversial. We aimed to investigate comprehensively the MRI predictors of cognitive impairment in confluent WML. Methods: Among 45 lacunar stroke patients who had confluent WML, we evaluated the association of executive function [Mattis Dementia Rating Scale - Initiation/Perseveration subscale (MDRS I/P)] and global cognition [Mini-Mental State Examination (MMSE)] with the volume of WML, measures of lacunes and microbleeds, and the volumes of 99 other specific brain regions. Results: Regression analyses showed that WML volume predicted performance on the MDRS I/P (β = -0.34, p = 0.016) independent of age. Volumes of cortical gray matter (cGM; β = 0.41, p = 0.003), the lateral fronto-orbital gyrus (β = 0.38, p = 0.01), superior frontal gyrus (β = 0.29, p = 0.04), lateral ventricle (β = -0.30, p = 0.04), and posterior limb of the internal capsule (β = 0.43, p = 0.002) predicted MDRS I/P performance independent of WML volume. Volumes of cGM, and the lateral fronto-orbital gyrus predicted MMSE performance as well. Conclusion: Atrophy along the frontosubcortical pathways and cGM predict cognition in confluent WML independent of WML volume. Copyright © 2007 S. Karger AG.",aged;article;brain atrophy;brain cortex;brain damage;brain function;brain hemorrhage;brain region;capsula interna;clinical article;cognition;cognitive defect;correlation coefficient;female;frontal lobe;gray matter;human;lateral brain ventricle;male;Mini Mental State Examination;nuclear magnetic resonance imaging;orbit;prediction;priority journal;rating scale;regression analysis;cerebrovascular accident;volumetry;white matter,"Mok, V. C. T.;Liu, T.;Lam, W. W. M.;Wong, A.;Hu, X.;Guo, L.;Chen, X. Y.;Tang, W. K.;Wong, K. S.;Wong, S.",2008,,,0,
2426,Effects of statins on the progression of cerebral white matter lesion : PPost hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study,"Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (β = 0.63, P < 0.001) and simvastatin treatment (β = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline. © 2009 Springer-Verlag.",antihypertensive agent;antithrombocytic agent;hemoglobin A1c;low density lipoprotein cholesterol;oral antidiabetic agent;placebo;simvastatin;triacylglycerol;adult;age;aged;article;brain size;cholesterol blood level;controlled study;diastolic blood pressure;disease course;disease severity;drug effect;female;follow up;hemoglobin blood level;human;ischemic heart disease;leukoaraiosis;major clinical study;male;middle cerebral artery occlusion;nuclear magnetic resonance imaging;post hoc analysis;priority journal;quantitative analysis;cerebrovascular accident;systolic blood pressure;treatment duration;treatment outcome;triacylglycerol blood level;white matter,"Mok, V. C. T.;Lam, W. W. M.;Fan, Y. H.;Wong, A.;Ng, P. W.;Tsoi, T. H.;Yeung, V.;Wong, K. S.",2009,,,0,
2427,Delayed-onset dementia after stroke or transient ischemic attack,"INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of >/=3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.","0 (Apolipoproteins E);0 (Phenanthrolines);0;(diethyl-1,3,6,8-tetrahydro-1,3,6,8-tetraoxobenzo(lmn)(3,8)phenanthroline-2,7-dia;cetate);0Z5B2CJX4D (Fluorodeoxyglucose F18);Adult;Aged;Aged, 80 and over;Apolipoproteins E/genetics;Brain/diagnostic imaging;Dementia/diagnostic imaging/ etiology;Female;Fluorodeoxyglucose F18;Follow-Up Studies;Humans;Ischemic Attack, Transient/ complications/diagnostic imaging/psychology;Longitudinal Studies;Male;Middle Aged;Phenanthrolines;Positron-Emission Tomography;Prospective Studies;Stroke/ complications/diagnostic imaging/psychology;Time Factors;Tomography, X-Ray Computed;Young Adult;Alzheimer's disease;Delayed-onset dementia;Small vessel disease;Stroke;Transient ischemic attack","Mok, V. C. T.;Lam, B. Y. K.;Wang, Z.;Liu, W.;Au, L.;Leung, E. Y. L.;Chen, S.;Yang, J.;Chu, W. C. W.;Lau, A. Y. L.;Chan, A. Y. Y.;Shi, L.;Fan, F.;Ma, S. H.;Ip, V.;Soo, Y. O. Y.;Leung, T. W. H.;Kwok, T. C. Y.;Ho, C. L.;Wong, L. K. S.;Wong, A.",2016,Nov,,0,
2428,The validity and reliability of chinese frontal assessment battery in evaluating executive dysfunction among Chinese patients with small subcortical infarct,"OBJECTIVES: Frontal Assessment Battery (FAB) is a valid and reliable screening test for evaluating executive dysfunction among whites with frontal and subcortical degenerative lesions. We studied the properties of a Chinese version of FAB (CFAB) in evaluating executive dysfunction among Chinese stroke patients with small subcortical infarct. METHODS: Concurrent validity was evaluated using Wisconsin Card Sorting Tst (WCST) and Mattis Dementia Rating Scale-Initiation/Perseveration Subset (MDRS I/P) among 41 controls and 30 stroke patients with small subcortical infarct. Discriminant validities of CFAB and its subitems were compared with those of Mini-Mental State Examination (MMSE). Internal consistency, test-retest, and interrater reliability of CFAB were evaluated. RESULTS: The CFAB had low to good correlation with various executive measures: MDRS I/P (r = 0.63, p < 0.001), number of category completed (r = 0.45, p < 0.001), and number of perseverative errors (r = -0.37, p < 0.01) of WCST. Among the executive measures, only number of category completed had significant but small contribution (6.5%, p = 0.001) to the variance of CFAB. A short version of CFAB using three items yielded higher overall classification accuracy (86.6%) than that of CFAB full version (80.6%) and MMSE (77.6%). Internal consistency (alpha = 0.77), test-retest reliability (rho = 0.89, p < 0.001), and interrater reliability (rho = 0.85, p < 0.001) of CFAB were good. CONCLUSION: Although CFAB is reliable, it is only moderately valid in evaluating executive dysfunction among Chinese stroke patients with small subcortical infarct. The clinical use of CFAB in the evaluation of executive dysfunction among this group of patients cannot be recommended at this stage.","Aged;*Asian Continental Ancestry Group;Brain/pathology/physiopathology;Cerebral Infarction/*diagnosis/ethnology/physiopathology;*Cross-Cultural Comparison;Dementia, Multi-Infarct/*diagnosis/ethnology/physiopathology;Diagnosis, Differential;Female;Frontal Lobe/pathology/*physiopathology;Hong Kong;Humans;Language;Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Middle Aged;Neurodegenerative Diseases/diagnosis/ethnology/physiopathology;*Neuropsychological Tests/statistics & numerical data;Observer Variation;Problem Solving/*physiology;Psychometrics;Reference Values;Reproducibility of Results;Statistics as Topic;Tomography, X-Ray Computed","Mok, V. C.;Wong, A.;Yim, P.;Fu, M.;Lam, W. W.;Hui, A. C.;Yau, C.;Wong, K. S.",2004,Apr-Jun,,0,
2429,Cognitive impairment and functional outcome after stroke associated with small vessel disease,"OBJECTIVES: Although stroke associated with small vessel disease (SSVD) can induce both motor and cognitive impairment, the latter has received less attention. We aimed to evaluate the frequency of the varying severity levels of cognitive impairment, the determinants of severe cognitive impairment, and the association of cognitive impairment with functional outcome after SSVD. METHODS: Consecutive patients admitted to hospital because of SSVD were assessed at 3 months after stroke. We performed a semi-structured clinical interview to screen for cognitive symptoms. Severity of cognitive symptoms was graded according to the Clinical Dementia Rating Scale (CDR). Performance on psychometric tests (Mini-Mental State Examination, Alzheimer's Disease Assessment Scale (cognition subscale), Mattis Dementia Rating Scale (initiation/perseverence subscale; MDRS I/P)) of patients of different CDR gradings was compared with that of 42 healthy controls. Basic demographic data, vascular risk factors, stroke severity (National Institute of Health Stroke Scale; NIHSS), pre-stroke cognitive decline (Informant Questionnaire on Cognitive Decline in the Elderly; IQCODE), functional outcome (Barthel index; BI), Instrumental Activities Of Daily Living; IADL), and neuroimaging features (site of recent small infarcts, number of silent small infarcts, white matter changes) were also compared among the groups. Regression analyses were performed to find predictors of severe cognitive impairment and poor functional outcome. RESULTS: Among the 75 included patients, 39 (52%) complained of cognitive symptoms. The number of patients in each CDR grading was as follows: 39 (52%) had a CDR of 0, 26 (34.7%) had a CDR of 0.5, 10 (13.3%) had a CDR of > or =1. Pre-stroke IQCODE and previous stroke predicted CDR> or =1. The NIHSS was associated with more impaired BI. The NIHSS and MDRS I/P contributed most to impaired IADL. CONCLUSIONS: Half of the patients with SSVD complained of varying severity of cognitive problems 3 months after stroke. Pre-stroke cognitive decline and previous stroke predict severe cognitive impairment post stroke. Stroke severity and executive dysfunction contribute most to a poor functional outcome.","Activities of Daily Living/classification;Aged;Alzheimer Disease/diagnosis;Brain/*blood supply;Cerebral Infarction/*diagnosis;Cognition Disorders/*diagnosis;Dementia, Multi-Infarct/*diagnosis;Diagnosis, Differential;Female;Follow-Up Studies;Humans;Magnetic Resonance Angiography;Male;Microcirculation/pathology;Middle Aged;Neuropsychological Tests","Mok, V. C.;Wong, A.;Lam, W. W.;Fan, Y. H.;Tang, W. K.;Kwok, T.;Hui, A. C.;Wong, K. S.",2004,Apr,,0,
2430,Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study,"Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.","0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors);0 (Placebos);AGG2FN16EV (Simvastatin);Aged;Brain Mapping;Cerebral Arteries/ drug effects/pathology;Cerebral Cortex/blood supply/ drug effects/pathology;Dementia, Vascular/drug therapy/pathology/prevention & control;Disease Progression;Double-Blind Method;Female;Humans;Hydroxymethylglutaryl-CoA Reductase Inhibitors/ pharmacology/therapeutic use;Image Processing, Computer-Assisted;Infarction, Middle Cerebral Artery/ drug therapy/pathology/physiopathology;Intracranial Arteriosclerosis/ drug therapy/pathology/prevention & control;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ drug effects/pathology;Placebos;Severity of Illness Index;Simvastatin/pharmacology/therapeutic use;Treatment Outcome","Mok, V. C.;Lam, W. W.;Fan, Y. H.;Wong, A.;Ng, P. W.;Tsoi, T. H.;Yeung, V.;Wong, K. S.",2009,May,,0,2431
2431,Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study,"Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.","Brain Mapping;Cerebral Arteries [drug effects] [pathology];Cerebral Cortex [blood supply] [drug effects] [pathology];Dementia, Vascular [drug therapy] [pathology] [prevention & control];Disease Progression;Double-Blind Method;Hydroxymethylglutaryl-CoA Reductase Inhibitors [pharmacology] [therapeutic use];Image Processing, Computer-Assisted;Infarction, Middle Cerebral Artery [drug therapy] [pathology] [physiopathology];Intracranial Arteriosclerosis [drug therapy] [pathology] [prevention & control];Magnetic Resonance Imaging;Nerve Fibers, Myelinated [drug effects] [pathology];Placebos;Severity of Illness Index;Simvastatin [pharmacology] [therapeutic use];Treatment Outcome;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia","Mok, V. C.;Lam, W. W.;Fan, Y. H.;Wong, A.;Ng, P. W.;Tsoi, T. H.;Yeung, V.;Wong, K. S.",2009,,10.1007/s00415-009-5008-7,0,
2432,Delayed-onset dementia after stroke or transient ischemic attack,"INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of >/=3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.",Alzheimer's disease;Delayed-onset dementia;Small vessel disease;Stroke;Transient ischemic attack,"Mok, V. C.;Lam, B. Y.;Wang, Z.;Liu, W.;Au, L.;Leung, E. Y.;Chen, S.;Yang, J.;Chu, W. C.;Lau, A. Y.;Chan, A. Y.;Shi, L.;Fan, F.;Ma, S. H.;Ip, V.;Soo, Y. O.;Leung, T. W.;Kwok, T. C.;Ho, C. L.;Wong, L. K.;Wong, A.",2016,Jun 18,10.1016/j.jalz.2016.05.007,0,
2433,Predictors for cognitive decline in patients with confluent white matter hyperintensities,"BACKGROUND: Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH. METHODS: We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippocampi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini-Mental State Examination, Mattis dementia rating scale--initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters. RESULTS: Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale--initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer's disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline. CONCLUSIONS: Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlipidemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer's pathology.","Aged;Atrophy/pathology;Brain/ pathology/physiopathology;Cognition Disorders/etiology/ pathology/physiopathology;Double-Blind Method;Female;Folic Acid/therapeutic use;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Secondary Prevention;Stroke/complications/drug therapy/ pathology;Vitamin B 12/therapeutic use;Vitamin B 6/therapeutic use;Vitamin B Complex/therapeutic use","Mok, V.;Xiong, Y.;Wong, K. K.;Wong, A.;Schmidt, R.;Chu, W. W.;Hu, X.;Lung Leung, E. Y.;Chen, S.;Chen, Y.;Tang, W. K.;Chen, X.;Ho, C. L.;Wong, K. S.;Wong, S. T.",2012,Oct,10.1016/j.jalz.2011.10.004,0,
2434,Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion,"OBJECTIVE: Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML. METHODS: Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale--Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke. RESULTS: WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey matter volume independently accounted for performance on both the MDRS I/P (beta=0.241, p=0.045) and MMSE (beta=0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left (beta=0.424, p<0.001) and right (beta=0.219, p=0.045) lateral frontal orbital gyri predicted MDRS I/P, whereas education (beta=0.385, p<0.001) and left lateral frontal orbital gyrus (beta=0.222, p=0.037) predicted MMSE. Volumes of WML and cognitively relevant brain regions were significantly associated. Seven patients with PIB imaging showed no uptake pattern typical of Alzheimer's disease, suggesting a predominantly vascular aetiology for the cognitive impairment and brain changes in these patients. CONCLUSIONS: Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.",Aged;Aging/ pathology/ psychology;Atrophy;Cerebral Amyloid Angiopathy/pathology;Cerebral Cortex/ pathology;Cognition Disorders/ pathology/ psychology;Double-Blind Method;Executive Function/physiology;Female;Frontal Lobe/ pathology;Homocysteine/antagonists & inhibitors;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Predictive Value of Tests;Regression Analysis;Stroke/prevention & control,"Mok, V.;Wong, K. K.;Xiong, Y.;Wong, A.;Schmidt, R.;Chu, W.;Hu, X.;Leung, E. Y.;Chen, S.;Chen, Y.;Tang, W. K.;Chen, X.;Ho, C. L.;Wong, K. S.;Wong, S. T.",2011,Jan,10.1136/jnnp.2009.201665,0,
2435,Determinants of prestroke cognitive impairment in stroke associated with small vessel disease,"Understanding the determinants of prestroke cognitive impairment (PCI) in stroke associated with small vessel disease (SVD) may shed light on how to prevent further cognitive deterioration after stroke. We administered the Informant Questionnaire on Cognitive Decline (IQCODE) to close informants of 78 consecutive stroke patients who had SVD. PCI, as defined by an average score of IQCODE > or =3.4 was found in 19 (24%) patients. Regression analyses were performed on the following risk factors for PCI: age, years of education, gender, previous stroke, volume of white matter changes, measures of silent lacunes, cerebral atrophy index, medial temporal lobe atrophy and frontal lobe atrophy. Multivariate regression analyses revealed that only cerebral atrophy index (OR 1.5, CI 1.2-1.9, p < 0.001) predicted PCI among patients with SVD.","Aged;Atrophy;Brain/pathology;Cerebrovascular Disorders/complications/*psychology/radiography;Cognition Disorders/etiology/*psychology/radiography;Dementia, Vascular/etiology/psychology/radiography;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Stroke/etiology/*psychology/radiography;Tomography, X-Ray Computed","Mok, V.;Wong, A.;Tang, W. K.;Lam, W. W.;Fan, Y. H.;Richards, P. S.;Wong, K. T.;Ahuja, A. T.;Wong, K. S.",2005,,10.1159/000087310,0,
2436,Neuroimaging determinants of cognitive performances in stroke associated with small vessel disease,"BACKGROUND AND PURPOSE: Controversies still exist as to the neuroimaging determinants of cognitive impairment in cerebral small vessel disease (SVD). The authors studied the neuroimaging correlates of cognitive performances among patients with stroke associated with SVD. METHODS: The authors per formed cerebral computed tomography, magnetic resonance imaging, and diffusion-weighted imaging among 74 consecutive patients admitted to the acute stroke unit because of stroke associated with SVD. They examined the association between cognitive performances and the following neuroimaging features: volume of white matter changes (WMC), multiplicity of lacunae, location of lacunae, total cerebral atrophy, and frontal and medial temporal lobe atrophy. RESULTS: Apart from age and education, univariate linear regression analyses revealed that WMC volume, presence of thalamic lacunae, cerebral atrophy, and left frontal lobe atrophy predicted performance on the Mini-Mental State Examination while WMC volume, presence of thalamic infarcts, cerebral atrophy, and frontal lobe atrophy of both sides predicted performance on the Mattis Dementia Rating Scale-Initiation/Preservation subscale. In the multivariate analyses, education (R2=0.22, P<.001), left frontal lobe atrophy (R2=0.10, P=.004), and presence of thalamic lacunae (R2=0.04, P=.049) were found to predict performance on the Mini-Mental State Examination while age (R2=0.23, P<.001) and presence of thalamic lacunae (R2=0.08, P=.011) were found to predict performance on the Mattis Dementia Rating Scale-Initiation/Preservation. CONCLUSIONS: Among patients with stroke associated with SVD, thalamic lacunae and frontal lobe atrophy are key determinants of cognitive performances.","Age Factors;Aged;Atrophy;Brain Infarction/physiopathology;Cerebral Arterial Diseases/ complications;Cerebral Cortex/pathology;Cognition/ physiology;Dementia/physiopathology;Diffusion Magnetic Resonance Imaging;Educational Status;Female;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Neuropsychological Tests;Prospective Studies;Psychomotor Performance/physiology;Stroke/pathology/ physiopathology;Temporal Lobe/pathology;Thalamus/blood supply;Tomography, X-Ray Computed","Mok, V.;Chang, C.;Wong, A.;Lam, W. W.;Richards, P. S.;Wong, K. T.;Wong, K. S.",2005,Apr,10.1177/1051228404274304,0,
2437,Blink Reflex May Help Discriminate Alzheimer Disease From Vascular Dementia,"PURPOSE: Dementia has several different etiologies, and vascular dementia (VaD) is considered the second leading cause of dementia after Alzheimer disease (AD). Various studies used blink reflex in different spectrum of neurological diseases as a complementary diagnostic test. We performed blink test in AD, VaD, and mixed dementia to investigate different usefulness of blink reflex in differentiating these types of dementia. METHODS: Blink reflex was performed for patients with AD (n = 18), VaD (n = 17), mixed dementia (n = 19), and normal subjects (n = 20). The absolute latency of R1, R2, and contralateral R2 (R2c) was determined and then compared with normal values. We used ROC curve to determine the screening cut-off value for R2 and R2c to discriminate dementia with vascular component and AD. RESULTS: The mean age +/- SD of patients was 71.61 +/- 8.23, 66.71 +/- 11.48, 75.26 +/- 8.32, and 66.60 +/- 3.91 years in 4 groups of AD, VaD, mixed dementia, and normal, respectively. R2 and R2c were recorded in fewer number of subjects with VaD or mixed dementia than AD and normal subjects. For mean R2 latency higher than 45 milliseconds, the sensitivity and specificity were 42% and 100%, respectively, and for latency higher than 45 milliseconds, the sensitivity and specificity were 72% and 89%, respectively. CONCLUSIONS: R2 and R2c components of blink reflex could specifically discriminate between Alzheimer and dementia with vascular component. The interruption of descending corticoreticular pathways by small infarcts could explain it.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis;Analysis of Variance;Blinking/*physiology;Brain/pathology;Dementia, Vascular/*diagnosis;Female;Functional Laterality/physiology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neurophysiology;Psychiatric Status Rating Scales;ROC Curve","Mohammadian, F.;Noroozian, M.;Nafissi, S.;Fatehi, F.",2015,Dec,10.1097/wnp.0000000000000214,0,
2438,Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia,"PURPOSE: To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction. MATERIALS AND METHODS: This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the HIV-positive subjects having HIV-associated dementia; 63 men, 31 women; mean age, 40 years) were determined with proton (hydrogen 1 [(1)H]) MR spectroscopic imaging. HIV-positive subjects underwent neuropsychological testing and blood and cerebrospinal fluid (CSF) analysis. Factor analysis was utilized to determine associations between metabolites across regions. Analysis of variance and t tests were used to isolate differences between cohorts. RESULTS: A ""Cho factor"" differentiated seronegative controls from HIV-infected cohorts, indicating elevated Cho levels across deep gray and white matter regions of HIV-positive individuals. An ""NAA factor"" differentiated those with dementia from those without and correlated best with psychomotor and executive function tests. A ""Cr factor"" indicated Cr elevations correlated with CSF monocyte chemoattractant protein-1 levels. NAA and Cr factor scores were strongly weighted to metabolite changes in white matter regions. CONCLUSION: These results highlight the importance of white matter involvement in HIV-associated dementia and support the current pathogenesis model of glial cell proliferation in HIV infection, denoted by regional Cho elevations, and neuronal dysfunction and/or death, denoted by NAA decreases, associated with dementia. Factor analysis of MR spectroscopic imaging data is a useful method for determining regional metabolic variations in HIV infection and its neuropsychological correlates.","AIDS Dementia Complex/ metabolism;Adult;Analysis of Variance;Aspartic Acid/analogs & derivatives/metabolism;Case-Control Studies;Chi-Square Distribution;Choline/metabolism;Creatine/metabolism;Factor Analysis, Statistical;Female;HIV Infections/ metabolism;Humans;Magnetic Resonance Spectroscopy;Male;Neuropsychological Tests","Mohamed, M. A.;Lentz, M. R.;Lee, V.;Halpern, E. F.;Sacktor, N.;Selnes, O.;Barker, P. B.;Pomper, M. G.",2010,Feb,10.1148/radiol.09081867,0,
2439,Brain metabolism and cognitive impairment in HIV infection: A 3-T magnetic resonance spectroscopy study,"Background and Purpose: Human immunodeficiency virus (HIV)-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 T. Higher magnetic field strengths (such as 3 T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3-T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln). Methods: Eighty-six HIV+ subjects were evaluated at 3 T using quantitative short echo time single-voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into three groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia (clinical MSK stage=0.5), and 34 had dementia (HAD) (MSK≥1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed and motor and psychomotor speed. Between-group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive results. Results: FWM Glx was lower in HAD (8.1±2.1 mM) compared to both the MCI (9.17±2.1 mM) and NC groups (10.0±1.6 mM) (P=.006). FWM myo-inositol (mI) was higher in HAD (4.15±0.75 mM) compared to both MCI (3.86±0.85 mM) and NC status (3.4±0.67 mM) (P=.006). FWM Glx/creatine (Cr) was lower and FWM mI/Cr was significantly higher in the HAD compared to the MCI and NC groups (P=.01 and P=.004, respectively). BG N-acetyl aspartate (NAA) was lower in the HAD group (6.79±1.53 mM), compared to the MCI (7.5±1.06 mM) and NC (7.6±1.01 mM) groups (P=.036). Significant negative correlations were observed between Glu, Glx and NAA concentrations with Trail-Making Test B (P=.006, P=.0001 and P=.007, respectively), and significant positive correlation was found with the Digit symbol test (P=.02, P=.002 and P=.008, respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved Pegboard nondominant hand (P=.02 and P=.04, respectively). Conclusion: Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. Three-Tesla MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection. © 2010 Elsevier Inc.",creatine;glutamic acid;glutamine;inositol;n acetylaspartic acid;adult;article;attention;basal ganglion;brain metabolism;cognitive defect;controlled study;female;frontal cortex;HIV associated dementia;human;Human immunodeficiency virus infection;major clinical study;male;mental performance;mild cognitive impairment;motor performance;neuropsychological test;nuclear magnetic resonance spectroscopy;priority journal;white matter;working memory;3-T Philips Intera scanner,"Mohamed, M. A.;Barker, P. B.;Skolasky, R. L.;Selnes, O. A.;Moxley, R. T.;Pomper, M. G.;Sacktor, N. C.",2010,,,0,
2440,Increased differentiation of intracranial white matter lesions by multispectral 3D-tissue segmentation: Preliminary results,"MRI is a very sensitive imaging modality, however with relatively low specificity. The aim of this work was to determine the potential of image post-processing using 3D-tissue segmentation technique for identification and quantitative characterization of intracranial lesions primarily in the white matter. Forty subjects participated in this study: 28 patients with brain multiple sclerosis (MS), 6 patients with subcortical ischemic vascular dementia (SIVD), and 6 patients with lacunar white matter infarcts (LI). In routine MR imaging these pathologies may be almost indistinguishable. The 3D-tissue segmentation technique used in this study was based on three input",,"Mohamed, F. B.;Vinitski, S.;Gonzalez, C. F.;Faro, S. H.;Lublin, F. A.;Knobler, R.;Gutierrez, J. E.",2001,2001,,0,
2441,Cerebral white matter disease is associated with Alzheimer pathology in a prospective cohort,"BACKGROUND: Although magnetic resonance imaging (MRI)-detected white matter disease has been correlated with cognitive decline in the elderly individuals, it is unclear whether white matter disease is primarily responsible for the cognitive deterioration or whether another process is common to both white matter disease and dementia. METHODS: We examined the relationship between Alzheimer-type brain pathology at autopsy and MRI-detected cerebral white matter disease in 50 participants from the Baltimore Longitudinal Study of Aging Autopsy Program, a prospective study of aging that includes detailed cognitive assessments. RESULTS: White matter disease was quantitated in pre- and postmortem MRI scans using the Cardiovascular Health Study (CHS) criteria in a blinded manner. We found that several measures of Alzheimer's disease (AD) pathology, including the Consortium to Establish a Registry for Alzheimer's Disease score, Braak score, and a composite AD pathology score, along with hypertension, were significantly associated with CHS white matter score using univariate and multivariate ordinal regression. In contrast, amyloid angiopathy was not independently associated with CHS score. Although a clinical diagnosis of dementia was associated with CHS score in univariate analysis, the association disappeared after accounting for AD pathology. CONCLUSION: AD pathology at autopsy is associated with MRI-detected cerebral white matter disease. This relationship may explain, in part, the association between cerebral white matter disease and cognitive decline in the elderly individuals.","Aged;Aging/pathology;Alzheimer Disease/ pathology;Brain/ pathology;Cognition Disorders/ pathology;Cohort Studies;Humans;Magnetic Resonance Imaging;Nerve Fibers, Myelinated/ pathology","Moghekar, A.;Kraut, M.;Elkins, W.;Troncoso, J.;Zonderman, A. B.;Resnick, S. M.;O'Brien, R. J.",2012,Oct,10.1016/j.jalz.2012.04.006,0,
2442,The cerebrovascular pathology in Alzheimer's disease and its influence on clinical variables,"Vascular pathology is frequently found in the brains of patients with Alzheimer's disease (AD). The aim of this study is to assess the frequency of vascular pathology in the brain in AD patients in a systematic manner and its clinical significance at presentation. A series of 51 patients with mild to moderate AD were consecutively enrolled. At baseline, every patient underwent the following clinical scales: Mini-Mental, Clinical Dementia Rating Scale, Ischemic Scale, Blessed Dementia Rating Scale, Alzheimer's Disease Assessment Scale Cognitive Subscale, Neuropsychiatric Inventory, and an Activities of Daily Living Scale (Disability Assessment for Dementia). We also carried out magnetic resonance imaging of the brain and color echo Doppler of carotids to measure the intima-media thickness. White matter hyperintensities were quantitatively evaluated with the Wahlund scale. We did not find correlation between intima-media thicknesses of carotids and clinical scales and between the Wahlund scale and clinical scales. The presence or absence of both microinfarctions and hypertension had no influence in the scores of the clinical scales. We conclude that the vascular component is common in AD but only as coincident pathology. © 2008 Sage Publications.",,"Modrego, P. J.;Rios, C.;Prez Trullen, J. M.;Errea, J. M.;Garca-Gmara, M. J.;Sanchez, S.",2008,February-March,,0,
2443,[Binswanger's disease and its relationship with vascular risk factors] Leucoaraiosis y su relacion con los factores de riesgo vascular,"INTRODUCTION: Lesions in the periventricular white matter are a quite common neuroradiological finding in older patients. They are called leukoaraiosis and can be associated to several syndromes. OBJECTIVE: To study the relation between leukoaraiosis and the different vascular risk factors that can be involved in its development. METHOD: Fifty consecutive patients with leukoaraiosis in CT scan were included as well as fifty age and sex-matched controls; all of them belonged to the same population. Previously vascular risk factors were defined according to strict criteria. RESULTS: The commonest vascular risk factor was arterial hypertension, in second place previous cerebrovascular accidents and in third place heart diseases. There was a very significant difference for hypertension in the univariant analysis, which was subsequently confirmed in the multivariant analysis. CONCLUSIONS: The vascular risk factor most strongly associated to leukoaraiosis was arterial hypertension followed by cerebrovascular disease and heart diseases. The remaining of the analysed factors had a insignificant prediction power.","Aged;Aged, 80 and over;Cardiovascular Diseases/ complications;Case-Control Studies;Dementia, Vascular/ etiology;Female;Humans;Male;Middle Aged;Odds Ratio;Regression Analysis;Retrospective Studies;Risk Factors","Modrego Pardo, P. J.;Perez Trullen, J. M.",1994,Sep,,0,
2444,[Binswanger's disease and its relationship with vascular risk factors],"INTRODUCTION: Lesions in the periventricular white matter are a quite common neuroradiological finding in older patients. They are called leukoaraiosis and can be associated to several syndromes. OBJECTIVE: To study the relation between leukoaraiosis and the different vascular risk factors that can be involved in its development. METHOD: Fifty consecutive patients with leukoaraiosis in CT scan were included as well as fifty age and sex-matched controls; all of them belonged to the same population. Previously vascular risk factors were defined according to strict criteria. RESULTS: The commonest vascular risk factor was arterial hypertension, in second place previous cerebrovascular accidents and in third place heart diseases. There was a very significant difference for hypertension in the univariant analysis, which was subsequently confirmed in the multivariant analysis. CONCLUSIONS: The vascular risk factor most strongly associated to leukoaraiosis was arterial hypertension followed by cerebrovascular disease and heart diseases. The remaining of the analysed factors had a insignificant prediction power.","Aged;Aged, 80 and over;Cardiovascular Diseases/*complications;Case-Control Studies;Dementia, Vascular/*etiology;Female;Humans;Male;Middle Aged;Odds Ratio;Regression Analysis;Retrospective Studies;Risk Factors","Modrego Pardo, P. J.;Perez Trullen, J. M.",1994,Sep,,0,
2445,Central motor conduction time and regional cerebral blood flow in patients with leuko-araiosis,"Central motor conduction time (CMCT) and regional cerebral blood flow were investigated in 21 patients with leuko-araiosis. The severity of dementia was examined using mini-mental state examination. The head magnetic stimulation was performed using an SMN-1100 magnetic stimulator and a round coil with a diameter of 17 cm. The regional cerebral blood flow was measured using the stable xenon computed tomography method. The CMCT was significantly longer in the patients with dementia than in the patients without dementia. The blood flows in the parietal cortex, frontal white matter and thalamus were significantly lower in the patients with dementia than in the patients without dementia. There were significant negative correlations between the CMCT and the blood flows in the frontal cortex, temporal cortex, frontal white matter and thalamus. The significant negative correlations suggest that the prolongation of CMCT in patients with leuko-araiosis is related to the decrease in regional cerebral blood flows.","Aged;Brain/pathology/radiography;*Cerebrovascular Circulation;Cerebrovascular Disorders/pathology/*physiopathology/radiography;Dementia/pathology/*physiopathology/radiography;Female;Humans;Magnetic Resonance Imaging;*Magnetics;Male;Middle Aged;*Neural Conduction;Tomography, X-Ray Computed","Mochizuki, Y.;Oishi, M.;Takasu, T.",1998,Sep 18,,0,
2446,Cognitive impairment and diffuse white matter atrophy in alcoholics,"Objective: Diffuse brain white matter atrophy is often seen in chronic alcoholics, but its relation with cognitive impairment remains to be solved. In order to address this issue, in alcoholics with cognitive impairment at different levels, we studied relations of the central sensory conduction time (CSCT) or brain magnetic resonance imaging (MRI) findings with the cognitive function. Methods: Subjects were 35 alcoholics with mild cognitive impairment (mini-mental state examination score, MMSE, ≥24; mean±SD, 27.7±1.9), 12 with moderate to severe cognitive impairment (MMSE<24; 20.3±2.7), 15 with Alzheimer's disease (AD) (MMSE, 18.9±4.3) (disease control) and 20 healthy volunteers (MMSE, 28.5±1.6) (normal control). Median nerve SEPs were recorded in the all subjects, and the latencies and amplitudes of their N9, N11, P13/14, N20 and P25 components were measured. The ventriculocranial ratio (VCR) and the width of cortical sulci were measured on MRIs. These physiological parameters and MRI findings were compared between the 4 groups of the subject, and correlations between those all features were also analyzed. Results: CSCT and VCR were significantly greater in alcoholics with moderate to severe cognitive impairment than those in the other 3 groups. Pearson's product-moment correlation analyses of the alcoholics disclosed that both the CSCT and VCR had significant negative correlations with the MMSE score. Moreover, the CSCT and VCR were positively correlated. Conclusions: Both physiological and morphological estimates of the white matter function (CSCT and VCR) had a significant correlation with the cognitive dysfunction. Significance: The diffuse white matter atrophy may be one of the factors causing cognitive impairment in chronic alcoholics. © 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.",,"Mochizuki, H.;Masaki, T.;Matsushita, S.;Ugawa, Y.;Kamakura, K.;Arai, H.;Motoyoshi, K.;Higuchi, S.",2005,1,,0,
2447,Progressive supranuclear palsy presenting with primary progressive aphasia - Clinicopathological report of an autopsy case,"We report a Japanese autopsy case of progressive supranuclear palsy (PSP). The male patient was 74 years old at the time of death. At age 64, he developed non-fluent aphasia that progressed slowly over 8 years, eventually associated with behavioral abnormality, postural instability, and dysphagia at 2 years prior to his death. Magnetic resonance imaging of the brain at age 73 demonstrated marked atrophy of the frontal lobes, particularly on the left side. Neuropathological examination revealed the typical pathology of PSP: loss of neurons, gliosis, occurrence of neurofibrillary tangles, oligodendroglial coiled bodies, and tuft-shaped astrocytes in the frontal cortex, associated with argyrophilic threads in the underlying white matter, in the basal ganglia, including the thalamus, globus pallidus, and subthalamic nucleus, and in the brainstem nuclei, including the substantia nigra, pontine nucleus, and inferior olivary nucleus. No astrocytic plaques or ballooned neurons were observed. Protein analysis revealed accumulation of hyperphosphorylated tau of 68 and 64 kDa consisting of the four repeat tau isoforms. We conclude that the present case represented PSP with an 8-year history of primary progressive aphasia (PPA). Although focal cortical symptoms in PSP are rare or absent, we should keep in mind the possibility of atypical PSP in which cortical pathology is predominant particularly in the frontal lobe, and could result in PPA.",,"Mochizuki, A.;Ueda, Y.;Komatsuzaki, Y.;Tsuchiya, K.;Arai, T.;Shoji, S.",2003,1,,0,
2448,Cerebellar ataxia with elevated cerebrospinal free sialic acid (CAFSA),"In order to identify new metabolic abnormalities in patients with complex neurodegenerative disorders of unknown aetiology, we performed high resolution in vitro proton nuclear magnetic resonance spectroscopy on patient cerebrospinal fluid (CSF) samples. We identified five adult patients, including two sisters, with significantly elevated free sialic acid in the CSF compared to both the cohort of patients with diseases of unknown aetiology (n 144; P < 0.001) and a control group of patients with well-defined diseases (n 91; P < 0.001). All five patients displayed cerebellar ataxia, with peripheral neuropathy and cognitive decline or noteworthy behavioural changes. Cerebral MRI showed mild to moderate cerebellar atrophy (5/5) as well as white matter abnormalities in the cerebellum including the peridentate region (4/5), and at the periventricular level (3/5). Two-dimensional gel analyses revealed significant hyposialylation of transferrin in CSF of all patients compared to age-matched controls (P < 0.001)a finding not present in the CSF of patients with Salla disease, the most common free sialic acid storage disorder. Free sialic acid content was normal in patients' urine and cultured fibroblasts as were plasma glycosylation patterns of transferrin. Analysis of the ganglioside profile in peripheral nerve biopsies of two out of five patients was also normal. Sequencing of four candidate genes in the free sialic acid biosynthetic pathway did not reveal any mutation. We therefore identified a new free sialic acid syndrome in which cerebellar ataxia is the leading symptom. The term CAFSA is suggested (cerebellar ataxia with free sialic acid).",ganglioside;sialic acid;transferrin;adult;article;behavior change;biosynthesis;brain region;cell culture;cerebellar ataxia;cerebellar ataxia with free sialic acid;cerebellum;cerebellum atrophy;cerebrospinal fluid;clinical article;cohort analysis;comparative study;control group;controlled study;disease severity;female;fibroblast;gene sequence;glycosylation;human;human cell;in vitro study;male;mental deterioration;metabolic disorder;nerve biopsy;nuclear magnetic resonance imaging;nucleotide sequence;peripheral neuropathy;priority journal;proton nuclear magnetic resonance;sialic acid storage disease;two dimensional gel electrophoresis;white matter,"Mochel, F.;Sedel, F.;Vanderver, A.;Engelke, U. F. H.;Barritault, J.;Yang, B. Z.;Kulkarni, B.;Adams, D. R.;Clot, F.;Ding, J. H.;Kaneski, C. R.;Verheijen, F. W.;Smits, B. W.;Seguin, F.;Brice, A.;Vanier, M. T.;Huizing, M.;Schiffmann, R.;Durr, A.;Wevers, R. A.",2009,,,0,
2449,Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features,"The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.","Adult;Aged;Animals;CADASIL/ genetics;Codon, Nonsense;Exons/genetics;Female;Humans;Italy;Male;Mice;Middle Aged;RNA, Messenger;Receptors, Notch/ genetics;Signal Transduction/genetics/physiology;Young Adult","Moccia, M.;Mosca, L.;Erro, R.;Cervasio, M.;Allocca, R.;Vitale, C.;Leonardi, A.;Caranci, F.;Del Basso-De Caro, M. L.;Barone, P.;Penco, S.",2015,Jan,10.1016/j.neurobiolaging.2014.08.021,0,
2450,Memantine in vascular dementia,"The uncompetitive N-methyl-D-aspartate (NMDA) antagonist memantine was tested against placebo in two randomized controlled trials. In total, 900 patients suffering from mild-to-moderate ""probable"" VaD (according to NINDS-AIREN criteria) were included. In these prospective, 2-arm parallel, multicenter trials conducted in the United Kingdom (MMM500) and in France (MMM300), patients suffering from ""probable"" vascular dementia (according to NINDS-AIREN criteria) were recruited. Active treatment in both trials was memantine at the standard daily dose of 10 mg b.i.d. The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) was a primary endpoint in both trials, and in both trials a statistically significant difference was seen between treatment groups after 28 weeks. In a pooled analysis of the data, various subgroups were examined. In a first analysis, patients were stratified by their severity of dementia (measured by the MMSE total scores at baseline). In this analysis, memantine was superior to placebo in all subgroups, but the magnitude of effect was clearly more pronounced in the more severely demented patients. A second analysis stratified the patients by the neuroradiological findings at baseline (""small vessel"" versus ""large vessel"" type of VaD). The cognitive benefit by memantine treatment was larger for the small vessel group and, interestingly, also the decline in the placebo group was faster in the small vessel patients. In these trials, memantine at a dose of 10 mg b.i.d. was safe and very well tolerated with a frequency of dropouts due to adverse events that was close to placebo.","Alzheimer Disease [diagnosis] [drug therapy];Brain [pathology] [radiography];Dementia, Vascular [diagnosis] [drug therapy];Dopamine Agents [therapeutic use];Magnetic Resonance Imaging;Memantine [therapeutic use];Neuropsychological Tests;Tomography, X-Ray Computed;Aged[checkword];Humans[checkword];Sr-dementia","Möbius, H. J.;Stöffler, A.",2003,,10.1017/s1041610203009219,0,
2451,New approaches to clinical trials in vascular dementia: memantine in small vessel disease,"Although criteria for the diagnosis of vascular dementia (VaD) are established, the diagnostic concept is still controversial and there is no regulatory guidance for clinical drug development. Clinical trials in VaD present a number of pitfalls and challenges and, so far, no compound has received regulatory approval for this indication. The methodological issues of clinical VaD trials are discussed using the development of memantine for this indication as an example. In a pooled analysis of two placebo-controlled trials with the NMDA-antagonist memantine in VaD, the cognitive benefit by memantine treatment was more pronounced for patients with 'small vessel disease' than for those with other neuroradiological findings at baseline. In a subgroup of patients with 'large vessel disease' or macrolesions, there was less cognitive decline among the placebo patients. It may therefore be helpful to use predefined diagnostic subcategories in clinical studies in this indication. The findings further suggest that stroke or multiple infarctions may not be the primary reason for cognitive decline in VaD patients.","Cognition [drug effects];Dementia, Vascular [drug therapy] [psychology];Double-Blind Method;Excitatory Amino Acid Antagonists [therapeutic use];Magnetic Resonance Imaging;Memantine [therapeutic use];Neuropsychological Tests;Prospective Studies;Tomography, X-Ray Computed;Aged[checkword];Humans[checkword];Sr-dementia","Möbius, H. J.;Stöffler, A.",2002,,49153,0,
2452,Added value of automated clinical proton MR spectroscopy of the brain,"OBJECTIVE: A trial was conducted to establish the added diagnostic value of an automated proton MR spectroscopy (MRS) examination (PROBE). MATERIALS AND METHODS: The PROBE and MRS were compared for metabolite ratios of normal controls and 21 patients. In addition, PROBE was performed in either the occipital cortex (gray matter) or the parietal cortex (white matter) or, more rarely, within the confines of a focal lesion identified on MRI, using a GE Signa 1.5 T whole-body scanner, in 112 patients undergoing routine brain MRI. The trial was conducted in three different MR centers to establish percentage of positive findings with MRI vs. MRI plus MRS. RESULTS: Cerebral metabolite ratios (N-acetylaspartate/creatine, choline/creatine, myo-inositol/creatine) obtained by PROBE and MRS were similar. Metabolite profiles in dementia, head trauma, herpes encephalitis, hepatic and hypoxic encephalopathy, stroke, and tumor were identified using PROBE. The PROBE technique increased the number of positive findings (""added value"") achieved by MRI; the added value was 28, 21, and 93% for the three trial sites. CONCLUSION: With only minor variations, PROBE reproduces the cerebral metabolite patterns obtained with MRS. It significantly increases the diagnostic yield of routine neuroimaging and might be incorporated as a standard sequence in a cost-effective manner.","Adult;Aged;Aged, 80 and over;Automation;Brain/*metabolism;Brain Diseases/*metabolism;Child;Humans;Infant, Newborn;Magnetic Resonance Imaging/*methods;Magnetic Resonance Spectroscopy/*methods;Protons;Signal Processing, Computer-Assisted","Moats, R. A.;Watson, L.;Shonk, T.;Tokuyama, S.;Braslau, D.;Eto, R.;Mandigo, J. C.;Ross, B. D.",1995,May-Jun,,0,
2453,"Senile dementia of Alzheimer type characterized by laminar neuronal loss exclusively in the hippocampus, parahippocampus and medial occipitotemporal cortex","Seven cases of senile dementia of Alzheimer type (SDAT) with unusual clinico-pathological findings are reported. The patients showed neuronal loss in laminar pattern, with gliosis exclusively confined to the CA1 of the hippocampus, the area of the hippocampal gyrus (entorhinal cortex) and medial occipitotemporal cortex. This change was more pronounced in the oral region. The subcortical white matter showed more pronounced fibrillary gliosis than loss of myelin. Both Alzheimer's neurofibrillary tangles and senile plaques were less marked than those usually seen in SDAT. The mental disturbance started after the age of 65 in all patients. The main clinical feature was marked character change in addition to disturbance of cognitive function. Cranial computed tomography showed marked dilatation of the oral portion of the inferior horn of the lateral ventricle in the early stage. It was apparent that although the cases in this group could be incorporated within in the spectrum of SDAT, they could also be considered to represent a variant of SDAT. This group could contribute to an understanding of the clinico-pathological spectrum of SDAT as well as indicating ways of managing such patients.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/radiography;Atrophy/pathology;Cerebral Cortex/*pathology/radiography;Female;Gliosis/pathology;Hippocampus/*pathology/radiography;Humans;Limbic System/pathology/radiography;Male;Neurons/*pathology;Occipital Lobe/*pathology/radiography;Temporal Lobe/*pathology/radiography;Tomography, X-Ray Computed","Mizutani, T.;Amano, N.;Sasaki, H.;Morimatsu, Y.;Mori, H.;Yoshimura, M.;Yamanouchi, H.;Hayakawa, K.;Shimada, H.",1990,,,0,
2454,Deep white matter lesions on MRI in elderly patients with dizziness,"High intensity signals on T2-weighted magnetic resonance imaging (MRI) of cerebral white matter are common in aged people. A recent study suggests that these lesions increase with risk factors for stroke from arteriolosclerosis. Some investigators have identified a relationship between these white matter lesions and dementia or motor deficits. The clinical significance of these white matter lesions remains unclear. To investigate the relationship between these white matter lesions identified on magnetic resonance imaging and dizziness in elderly patients, we evaluated findings on brain MRI of patients with dizziness (n=108) and patients without dizziness (n=28) aged over 60 years old. Deep white matter hyperintense signals (DWMH) and periventricular hyperintensity (PVH) were graded using a qualitative rating scale (Fazekas et al.). Patients with dizziness, especially originating in the central nervous system, showed significantly more severe white matter lesions (grade 2-3). We suggest that older patients with severe white matter high intensity signals experience dizziness due to vascular insufficiency from arteriolosclerosis.",,"Mizuta, K.;Ando, K.;Kuze, B.;Murai, M.;Yokota, Y.;Yamada, N.;Aoki, M.;Ito, Y.",2006,Jun,,0,
2455,Two Japanese CADASIL families exhibiting Notch3 mutation R75P not involving cysteine residue,"Most previously reported mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) result in an odd number of cysteine residues within the epidermal growth factor (EGF)-like repeats in Notch3. We report here R75P mutation in two Japanese CADASIL families not directly involving cysteine residues located within the first EGF-like repeats. Probands in both families had repeated episodes of stroke, depression, dementia as well as T2 high-intensity lesions in the basal ganglia and periventricular white matter, but fewer white matter lesions in the temporal pole on MRI. These families provide new insights into the diagnosis and pathomechanisms of CADASIL. © 2008 The Japanese Society of Internal Medicine.",cysteine;epidermal growth factor;Notch3 receptor;adult;akinetic mutism;article;basal ganglion;brain hemorrhage;brain infarction;CADASIL;case report;convulsion;dementia;depression;dizziness;family;female;gene mutation;head injury;headache;human;neurologic examination;nuclear magnetic resonance imaging;pathogenesis;pedigree;pseudobulbar palsy;quadriplegia;cerebrovascular accident;thalamus;white matter,"Mizuno, T.;Muranishi, M.;Torugun, T.;Tango, H.;Nagakane, Y.;Kudeken, T.;Kawase, Y.;Kawabe, K.;Oshima, F.;Yaoi, T.;Itoh, K.;Fushiki, S.;Nakagawa, M.",2008,,,0,
2456,Evaluation of NOTCH3 Pro167Ser Variation in a Japanese Family with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy,,Notch3 receptor;brain infarction;CADASIL;exon;female;gene mutation;genetic screening;genetic variability;human;Japanese (people);letter;migraine;nuclear magnetic resonance imaging;pathogenicity;priority journal;sequence analysis;single strand conformation polymorphism;skin biopsy,"Mizuno, T.;Mizuta, I.;Tomimoto, H.",2016,,,0,
2457,Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine,"A 64-year-old woman was admitted to our hospital for recurrent stroke and cognitive impairment and was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Iodine-123 iodoamphetamine single photon emission computed tomography showed hypoperfusion in the whole brain, but cerebral blood flow increased dramatically after the administration of acetazolamide in the cerebral cortex. Lomerizine, a diphenylmethylpiperazine Ca2+ channel blocker, can selectively increase cerebral blood flow. Cognitive decline and cerebral hypoperfusion improved during 2-year administration of lomerizine in this CADASIL patient, and thus, lomerizine is a potential candidate for treating cognitive impairment in CADASIL patients. Copyright © 2009 by Lippincott Williams & Wilkins.",acetazolamide;acetylsalicylic acid;dipyridamole;etizolam;iofetamine i 123;lansoprazole;lomerizine;losartan;maprotiline;serotonin uptake inhibitor;sulpiride;absence of side effects;adult;article;brain perfusion;brain scintiangiography;CADASIL;case report;clinical feature;cognitive defect;depression;diffusion weighted imaging;drug withdrawal;female;human;priority journal;single photon emission computer tomography;unspecified side effect;aspirin,"Mizuno, T.;Kondo, M.;Ishigami, N.;Tamura, A.;Itsukage, M.;Koizumi, H.;Isayama, R.;Hosomi, A.;Nagakane, Y.;Tokuda, T.;Sugimoto, E.;Ushijima, Y.;Nakagawa, M.",2009,,,0,
2458,Alterations in neurotransmitter in multi-infarct dementia and senile dementia of Alzheimer's type,"Serum glutamate acid decarboxylase (GAD), serum L-aromatic acid decarboxylase (AAD) and serum dopamine-β-hydroxylase (DBH) activities were measured in 31 cases with multi-infarct dementia (MID) and 31 cases with senile dementia of Alzheimer's type (SDAT). Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured in cerebrospinal fluid of 6 cases with MID and 11 cases with SDAT. Patients with dementia were classified into the following three groups using Hasegawa's Dementia Rating (DR) Scale: subnormal, predementia and dementia. CT scanning exhibited a severe brain atrophy in SDAT patients with low DR score. The grade of dementia in SDAT cases was greater than that in MID cases. CT findings of MID cases showed diffuse or scattered low density and ventricular dilatation, but widening of cortical sulci was not prominent in most of MID cases. Serum GAD levels of MID and SDAT were decreased to 8.4 ± 2.7 I.U./L (p < 0.05) and 7.6 ± 2.6 I.U./L (p < 0.01), respectively, compared with the control level of 11.7 ± 5.2 I.U./L. Serum AAD levels of MID and SDAT did not exhibit a significant difference from the control level. The serum DBH level of SDAT was significantly lower (12.2 ± 8.8 I.U./L, p < 0.05) than the control level (17.1 ± 9.5 I.U./L), though that of MID exhibited no significant difference. The decrease in DBH level of SDAT was more prominent in the group with severe dementia (10.6 ± 7.2 I.U./L, p < 0.01) or with severe brain atrophy (10.1 ± 8.3 I.U./L, p < 0.01). HVA concentrations in MID (32.6 ± 11.9 ng/ml, p < 0.05) and in SDAT (30.7 ± 21.0 ng/ml, p < 0.05) were significantly lower than that in control cases (56.0 ± 24.6 ng/ml). 5-HIAA concentrations exhibited no significant difference either in MID or SDAT, though some cases with SDAT showed lowered concentrations of both HVA and 5-HIAA in the cerebrospinal fluid. Decreases in the activity of GABAnergic, dopaminergic, noradrenergic or serotonergic systems were indicated in patients with dementia, especially SDAT. It is suggested that the functions in neurotransmitter systems in demented persons are not disturbed only in the cholinergic system but also in other systems.",5 hydroxyindoleacetic acid;aromatic acid decarboxylase;dopamine beta monooxygenase;glutamate decarboxylase;homovanillic acid;unclassified drug;Alzheimer disease;article;brain infarction;central nervous system;diagnosis;etiology;major clinical study,"Miyata, S.;Yamao, S.;Nakamura, S.",1981,,,0,
2459,Multiple Intracerebral Microhemorrhages Associated with Primary Aldosteronism: A Case Report,"We have observed dot-like low intensity spots (a dot-like hemosiderin spot: dotHS) on T2*-weighted (T2*-w) MRI, subsequently diagnosed histologically as previous microbleeds associated with lipohyalinosis, amyloid angiopathy and cerebral small vessel disease (SVD) including an intracerebral hematoma (ICH) and a lacunar infarction. According to the literature, primary aldosteronism (PA), characterized by hypertension, is related to SVD. A 49 year-old female with a long history of untreated hypertension secondary to PA was admitted to our hospital for medical examinations on Jul 18th, 2000. She had the stepwise development of dementia, dysarthria and gait disturbance (right hemiparesis). CT and MRI demonstrated multiple lacunar infarctions. She was readmitted to our hospital on Jan 23rd, 2002. A neurological examination revealed right hemiparesis, dysarthria and consciousness disturbance. CT on admission demonstrated ICH in the left midbrain. Six days after the hemorrhage, T2*-w MRI showed thirty-two dotHSs in the basal ganglias and the cortical-subcortical regions. The incidence of ICH in patients with hypertension secondary to PA is reported to be higher than in patients with essential hypertension. Multiple dotHS may be associated with ICH, lacunar infarction, and severe microangiopathy related to hypertension secondary to PA.",adult;article;basal ganglion;brain hematoma;brain hemorrhage;brain infarction;case report;consciousness disorder;dementia;disease association;disease severity;dysarthria;female;gait disorder;hemiparesis;human;hyaline degeneration;hypertension;mesencephalon;microangiopathy;nuclear magnetic resonance imaging;primary hyperaldosteronism;vascular amyloidosis,"Miyata, K.;Imaizumi, T.;Horita, Y.;Hashimoto, Y.;Tanno, K.;Koide, A.;Niwa, J.",2003,,,0,
2460,A 78-year-old man with young onset parkinsonism and sudden death,"We report a right handed 78-year-old man with early onset parkinsonism. The patient had an onset of micrographia at 23 years of the age in 1939. Seven years later he started to drag his right foot, and at 38 years of age, he walked with small steps with festination. Tremor was also present in his right hand. His daily life was independent as a otorhinolaryngologist. He visited our clinic on March 24, 1977 when he was mentally sound and showed mild parkinsonism consisting of masked face, stooped posture, small step gait, bradykinesia, and right side dominant rigidity and tremor. He showed good response to trihexyphenidyl and amantadine HCl. Two month later, he developed dyskinesia and some worsening of parkinsonism, and was admitted to our hospital for the first time. He was treated with 400 to 600 mg/day of levodopa/carbidopa. He showed marked improvement, however, dyskinesia remained in his mouth. He was doing well until 77 years of age (June of 1993) when he developed hallucination and motor fluctuations. He was admitted again to our hospital on June 22, 1993. On admission, he was alert and appeared mentally sound. However, Hasegawa dementia scale was 18/30. Upward gaze was slightly restricted (3/5). Voice was somewhat small but no masking was noted. His posture was stooped and the gait was of small step. Dyskinesia was noted during walk. No rigidity nor tremor was noted. Deep tendon reflexes were lost but no sensory loss or motor weakness was noted. Routine laboratory studies were unremarkable. A cranial CT scan revealed only mild to moderate cortical atrophy. Motor and sensory conduction velocities were within normal limits, however, motor action potentials could not be obtained with stimulation to the right common peroneal nerve. He was treated with 600 mg/day of levodopa with carbidopa, 100 mg of amantadine HCl, 300 mg of Dops, and 25 mg of tiapride. He continued to show motor fluctuations, and was discharged on July 23, 1993. Since then his motor functions had become progressively worse with frequent falls, but he was still able to walk without support. On October 3 of 1994, he went to bed as usual. On the next morning, he was found dead in his bed at 9: 30. The patient was discussed in neurological CPC, and the chief discussant arrived at the conclusion that the patient had young onset Parkinson's disease with Lewy bodies in the substantia nigra. Opinions were divided between Parkinson's disease and Lewy body negative young onset parkinsonism. Postmortem examination revealed obstruction of the trachea by aspirated foods, and the cause of death appeared to have been suffocation by the foods. Macroscopically, the external appearance of the brain was unremarkable except for slight frontal atrophy. The substantia nigra showed depigmentation in the lateral part, but the pigmentation of the medial part was well preserved. Upon histologic examination, the number of pigmented neurons in the dorsomedial part was well preserved. In the lateral part, pigmented neurons were well preserved in the dorsal area, however, in the ventral area, only non pigmented neurons were seen; they appeared to be neurons in the pars reticulata. No gliosis was seen in any of the nigral areas. No Lewy bodies were seen in the remaining neurons. So-called immature neurons with rounded shape without neuromelanin could not be detected. The locus coeruleus neurons were well preserved. The putamen and the other basal ganglia structures were also intact. Slight myelin pallor was noted in the subcortical white matter, however, otherwise cerebral cortices were normal. The histology of this patient is unique in that only the ventrolateral part of the substantia nigra showed abnormal finding consisting of lack of pigmented neurons without ghosts. It is not clear whether the nigral change represents degeneration or a congenital 'hypoplasia.' To our knowledge, such a unique pathology of the substantia nigra has not been reported in the literature. Our patient may represent a new form of pathology manifesting parkinsonism of early onset.",amantadine;carbidopa plus levodopa;droxidopa;tiapride;trihexyphenidyl;aged;article;bradykinesia;brain atrophy;case report;cause of death;computer assisted tomography;fatality;hallucination;histology;human;Lewy body;male;medical specialist;onset age;parkinsonism;right handedness;sudden death;trachea obstruction;tremor,"Miyasaka, H.;Mori, H.;Saikawa, T.;Shirai, T.;Kondo, T.;Imai, H.;Mizuno, Y.",1996,,,0,
2461,Leukoaraiosis in relation to prognosis for patients with lacunar infarction,"BACKGROUND AND PURPOSE: Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction. METHODS: We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living. RESULTS: Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex. CONCLUSIONS: The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction.","Activities of Daily Living;Adult;Aged;Brain/ radiography;Cerebral Infarction/ complications;Dementia/epidemiology/ etiology;Demyelinating Diseases/ complications/etiology/radiography;Female;Humans;Male;Middle Aged;Prevalence;Prognosis;Survival Rate;Tomography, X-Ray Computed","Miyao, S.;Takano, A.;Teramoto, J.;Takahashi, A.",1992,Oct,,0,
2462,"Demographic, clinical, and radiologic predictors of neurologic deterioration in patients with acute ischemic stroke","One-third of patients with acute ischemic stroke develop early neurologic worsening, which is associated with increased mortality and long-term functional disability. We investigated the predictive factors for neurologic deterioration in patients with acute ischemic stroke within 1 week of onset. We retrospectively investigated 643 patients who were admitted within 2 days of acute ischemic stroke between April 2007 and March 2010. Neurologic deterioration was defined as an increase of 4 points or more in the National Institutes of Health Stroke Scale (NIHSS) score within 1 week of admission. We retrieved data on demographic and clinical characteristics, medications, and stroke subtypes. Out of 537 patients, deterioration was noted in 64 patients (11.9%; deterioration group). Multivariate analysis identified history of myocardial infarction (P <.001), NIHSS score ≥8 at onset (P <.001), high leukocyte count (P =.035), low-density lipoprotein cholesterol ≥140 mg/dL (P =.002), and hemoglobin A1c ≥7% (P =.006) as significant factors associated with deterioration. Branch atheromatous disease was more frequent in the deterioration group, and >90% of patients with deterioration either were discharged to nursing home care or died. Multivariate analysis of magnetic resonance imaging findings identified internal carotid/middle cerebral artery occlusion (each P <.001), striate capsular infarction (P =.030), pontine infarction (P =.047), and lesion size of 15-30 mm (P =.011) as independent factors associated with deterioration. Stroke patients with a high low-density lipoprotein level, high hemoglobin A1c level on admission, a history of myocardial infarction, and high NIHSS score are at high risk for neurologic deterioration. Patients with multiple risk factors for deterioration can benefit most from intensive monitoring. © 2013 by National Stroke Association.",,"Miyamoto, N.;Tanaka, Y.;Ueno, Y.;Kawamura, M.;Shimada, Y.;Tanaka, R.;Hattori, N.;Urabe, T.",2013,April,,0,
2463,Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors,"BACKGROUND: Homocysteine has been identified as a potential risk factor for stroke, cerebral small-vessel diseases (SVD), and dementia. OBJECTIVE: The present study aimed to investigate the predictive value of homocysteine levels on incident dementia while simultaneously controlling for MRI findings and vascular risk factors. METHODS: Within a Japanese cohort of participants with vascular risk factors in an observational study, we evaluated the association between baseline total homocysteine (tHcy) levels (per 1 mumol/L and the tertile of tHcy), the prevalence of MRI-findings at baseline, and incident all-cause dementia. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities, and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tHcy and each of MRI findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between tHcy and dementia. RESULTS: In the 643 subjects (age: 67.2 +/- 8.4 years, male: 59% ; education: 12.9 +/- 2.6 years), multivariable analyses adjusted for several potential confounders, including estimated glomerular filtration rate (eGFR) and intima-media thickness, showed that highest tHcy tertile was associated with lacunas, CMBs, and strictly deep CMBs. During the mean 7.3-year follow-up (range: 2-13), 47 patients were diagnosed with dementia (Alzheimer's disease: 24; vascular dementia: 18; mixed-type: 3; other: 2). After adjusting for age, gender, APOE varepsilon4, education, BMI, MMSE, hypertension, cerebrovascular events, eGFR, and MRI-findings, tHcy level (hazard ratios [HR]: 1.08, p = 0.043) and the highest tertile of tHcy (HR: 2.50, p = 0.047) for all-cause dementia remained significant. CONCLUSIONS: Our results provide additional evidence of tHcy that contributes to increased susceptibility to dementia risk.",Alzheimer's disease;cerebral small-vessel disease;dementia;estimated glomerular filtration rate;homocysteine;microbleeds;vascular dementia,"Miwa, K.;Tanaka, M.;Okazaki, S.;Yagita, Y.;Sakaguchi, M.;Mochizuki, H.;Kitagawa, K.",2015,,10.3233/jad-150458,0,
2464,Chronic kidney disease is associated with dementia independent of cerebral small-vessel disease,"Objective: To determine whether chronic kidney disease (CKD) is associated with incident dementia independent of cerebral small-vessel disease (SVD) in patients with vascular risk factors. Methods: Using data from a Japanese cohort of participants with vascular risk factors in an ongoing observational study from 2001, we evaluated the association between CKD at baseline and incident dementia. Baseline brain MRIwas used to determine SVD (lacunar infarction,white matter hyperintensities), medial-temporal atrophy, and subcortical atrophy.Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOE ε4 allele, educational level, baseline Mini-Mental State Examination score, cerebrovascular events, vascular risk factors, and MRI findings. Results: Of the 600 subjects (mean age 68 ± 8.3 years, 57% male, 12.8 ±6 2.6 years of education; CKD: 29%), 50 patients with incident dementia (Alzheimer disease: 24; vascular dementia: 18; mixed-type dementia: 5; other types: 3) were diagnosed during the median 7.5-year follow-up. CKD at baseline was associated with an increased risk of all-cause dementia in models adjusted for age, sex, educational level, and APOE e4 allele. The associations of CKD at baseline remained significant even after additional adjusting for MRI findings and confounding variables (hazard ratio: 1.96 [1.08-3.58], p 5 0.026). Conclusions: CKD is independently related to the risk of all-cause dementia in patients with vascular risk factors. Our results reinforce the hypothesis that CKD exerts deleterious effects on dementia incidence. © 2014 American Academy of Neurology.",aged;allele;Alzheimer disease;APOE epsilon4 gene;article;cardiovascular risk;cerebrovascular disease;chronic kidney disease;dementia;disease association;female;follow up;gene;human;major clinical study;male;mixed type dementia;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal,"Miwa, K.;Tanaka, M.;Okazaki, S.;Furukado, S.;Yagita, Y.;Sakaguchi, M.;Mochizuki, H.;Kitagawa, K.",2014,,,0,
2465,"Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia","BACKGROUND AND PURPOSE: Mixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small-vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin-6 (IL-6), C-reactive protein (CRP) and gene variants increase dementia risk. METHODS: In a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL-6, CRP levels, gene variants [interleukin-6 receptor (IL-6R), rs2228145; IL-6, rs2097677; CRP, rs3093059] and incident all-cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial-temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein Eepsilon4, education, cerebrovascular events, vascular risk factors and MRI findings. RESULTS: Of 803 subjects (mean 67.0 +/- 8.5 years, males 59%), during a mean of 7.5 +/- 3.2 years follow-up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed-type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL-6R variant (rs2228145), IL-6 levels (relative risk 1.68, P = 0.048) or highest tertile (relative risk 2.38, P = 0.031) for all-cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL-6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia. CONCLUSIONS: The deleterious effect of higher IL-6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL-6R variant.",,"Miwa, K.;Okazaki, S.;Sakaguchi, M.;Mochizuki, H.;Kitagawa, K.",2016,Mar,10.1111/ene.12921,0,
2466,Severe hypoxia and multiple infarctions resembling Creutzfeldt-Jakob disease,"Although neuropathological examination is still required for the definite diagnosis of Creutzfeldt-Jakob disease (CJD), specialised clinical assessment predicts probable CJD. Here we present a 73-year-old female patient presenting with rapid cognitive decline, visual, acoustic and cerebellar disturbances, ataxia and EEG changes compatible with early CJD stages. MRI revealed hyperintensities within the thalami, hypothalami, corpora mammillaria, the tectum and the cortex. Initial neuropathological examination showed severe cortical and subcortical spongiosis. However, both immunohistochemistry and Western blotting showed no pathological prion protein. Finally small infarctions affecting the tectum, tegmentum, corpora mammillaria and global hypoxic-ischaemic changes could be identified as the probable reason for the changes interpreted as CJD-related pathology. Hypoxic-ischaemic CNS alterations mainly affecting the supply area of the basilar artery should be ruled out in case of probable CJD. In addition, severe spongiosis can be misleading in the histological examination, suggesting the diagnosis of a prion-induced spongiform encephalopathy.",aged;anamnesis;article;ataxia;brain cortex;brain hypoxia;brain infarction;brain ischemia;brain spongiosis;case report;cerebellum disease;cerebrospinal fluid analysis;cognitive defect;Creutzfeldt Jakob disease;disease severity;electroencephalogram;female;hearing disorder;human;human tissue;hypothalamus;immunoblotting;immunohistochemistry;neurologic examination;neuropathology;nuclear magnetic resonance imaging;tegmentum;thalamus;visual disorder;Western blotting,"Mittelbronn, M.;Capper, D.;Bader, B.;Schittenhelm, J.;Haybaeck, J.;Weber, P.;Meyermann, R.;Kretzschmar, H. A.;Wiethölter, H.",2008,,,0,
2467,An autopsied case of interferon encephalopathy,"A 78-year-old male with renal carcinoma was treated with a high dose infusion of interferon-alpha (IFN-alpha) for eight months. The patient had evidence of organic brain syndrome such as dysfunction of memory, slowing of behavior, and development of mental confusion that appeared eight months after the treatment. MRI at the time of mental confusion revealed diffuse white matter lesions. Neuropathologic findings were compatible to Binswanger's disease and Senile Dementia of Alzheimer Type (SDAT), Preexisting neurologic abnormalities including intracerebral arteriosclerosis and cerebral atrophy may increase susceptibility to unacceptable severe IFN neurotoxicity.",alpha interferon;aged;article;brain disease;case report;controlled study;human;human tissue;intramuscular drug administration;kidney carcinoma;male;neurotoxicity,"Mitsuyama, Y.;Hashiguchi, H.;Murayama, T.;Koono, M.;Nishi, S.",1992,,,0,
2468,[Cerebrovascular dementia; correlation of computed and histopathologic findings],"Computed tomography is often insensitive to such lesions as atrophic demyelination, enlarged perivascular spaces and infarction in the periventricular white matter. In attempt to better understand the discrepancy between the pathologic and X-CT findings, the author correlated areas that had focal, patchy on X-CT and brains with gross and microscopic findings. Patients with cerebral strokes had larger volume infarcts characterized centrally by necrosis, axonal loss, and demyelination. The progressive subcortical vascular encephalopathy (Binswanger's disease) is characterized by ischemic demyelinization of white matter provoked by hypertensive vascular changes in small vessels and is usually accompanied by multiple lacunar infarcts in a periventricular area and the basal ganglia. Small, deep hemispheric infarcts may be of no clinical significance unless a sufficient aggregate of these occurs. It should be pointed out that many small infarcts are clinically silent, and chronic multifocal ischemia may be responsible for observed senescent changes in cerebral tissue. The extension of the infarcted area might be most important in the development of cerebrovascular dementia. Mixed forms of degenerative dementia and any type of cerebral vascular disease are common and account for 10-20% of all dementias.","Aged;Aged, 80 and over;Brain/*pathology;Cerebral Infarction/pathology/radiography;Dementia, Vascular/pathology/*radiography;Female;Humans;Intracranial Arteriosclerosis/pathology/radiography;Male;Middle Aged;*Tomography, X-Ray Computed","Mitsuyama, Y.",1989,Oct,,0,
2469,Lennox-Gastaut syndrome associated with leukoencephalopathy,"We report a 13-year-old boy with Lennox-Gastaut syndrome (LGS) associated with leukoencephalopathy. He was diagnosed with unclassified acute lymphocytic leukemia at the age of 3 years. After initial chemotherapy, he received intravenous methotrexate (total dosage 1,035 mg), intrathecal methotrexate (total dosage 221 mg), and whole brain irradiation (2,400 cGy). From about the age of 8 years, he developed slurred speech, hyperactivity, and mental deterioration. Cranial CT revealed calcification of the subcortical white matter. At age 9 years, he exhibited tonic seizures and atonic seizures. EEG showed diffuse slow spike-wave discharges, which are characteristic of LGS. Although multiple antiepileptic drugs have been prescribed, the frequency of seizures remains unchanged and his mental state is becoming progressively worse.","6-Mercaptopurine/administration & dosage;Adolescent;Anticonvulsants/therapeutic use;Antineoplastic Combined Chemotherapy Protocols/therapeutic use;Brain Damage, Chronic/*etiology;Calcinosis/*etiology;Cranial Irradiation/*adverse effects;Cytarabine/administration & dosage;Dementia/*etiology;Doxorubicin/administration & dosage;Electroencephalography;Epilepsy, Absence/drug therapy/etiology;Epilepsy, Generalized/*etiology;Humans;Injections, Spinal;Male;Methotrexate/administration & dosage/*adverse effects;Movement Disorders/*etiology;Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/radiotherapy;Prednisolone/administration & dosage;Radiation Injuries/*etiology;Syndrome;Vincristine/administration & dosage","Mitsufuji, N.;Ikuta, H.;Yoshioka, H.;Sawada, T.",1996,Jul,,0,
2470,Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment,"Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease.",Alzheimer's;Mri;diffusion;fixel;white matter,"Mito, R.;Raffelt, D.;Dhollander, T.;Vaughan, D. N.;Tournier, J. D.;Salvado, O.;Brodtmann, A.;Rowe, C. C.;Villemagne, V. L.;Connelly, A.",2018,Jan 4,,0,
2471,Volume of the cingulate and outcome in schizophrenia,"BACKGROUND: Previous studies indicated that schizophrenia patients have reduced frontal volumes in comparison with normal, but among schizophrenics, reduced volumes of the posterior (temporal, parietal and occipital) cortex were associated with poor outcome. We examined whether this pattern is seen within the anteroposterior arch of the cingulate gyrus. METHODS: MR images were acquired in 37 schizophrenia patients (Kraepelinian, n = 13; non-Kraepelinian, n = 24) and 37 controls, and CSF, gray and white matter volumes in individual Brodmann's areas (BA) of the cingulate arch (areas 25, 24, 23, 31, 30, 29) were assessed and examined in relation to outcome. RESULTS: Schizophrenia patients had significant gray matter reductions in the absolute (mm(3)) volume of Brodmann's area 24 in anterior cingulate and, when corrected for brain size, in the whole cingulate and retrosplenial (areas 29-30) cortex. White matter volumes were increased in right posterior cingulate (area 31). Schizophrenia patients also showed abnormal lateralization of white matter volumes in retrosplenial cortex (area 30) and had lower correlations between frontal and anterior cingulate regions than controls. Poor-outcome subgroup exhibited significant bilateral gray matter deficits in posterior cingulate and retrosplenial cortices compared to good-outcome patients, while no white matter increases in these areas were seen. CONCLUSIONS: Poor outcome was associated with gray matter deficits in posterior cingulate while compensatory white matter increases in dorsal posterior regions may be related to better outcome. Possible consequences of this may include thought disorder, disturbance of consciousness, treatment resistance, and cognitive decline indicative of a dementing process as a superimposed or inherent part of this schizophrenia subtype.",Adult;Aged;Cognition Disorders/diagnosis/physiopathology;Female;Functional Laterality;Gyrus Cinguli/ abnormalities/physiopathology;Hospitalization;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Schizophrenia/ diagnosis/physiopathology/therapy;Surveys and Questionnaires;Thinking;Treatment Outcome,"Mitelman, S. A.;Shihabuddin, L.;Brickman, A. M.;Hazlett, E. A.;Buchsbaum, M. S.",2005,Jan 1,10.1016/j.schres.2004.02.011,0,
2472,"Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study","Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 +/- 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 +/- 0.037 SD/SD, P<0.001), grey matter (-0.079 +/- 0.038 SD/SD, P = 0.038) and white matter (-0.128 +/- 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 +/- 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 +/- 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 +/- 0.039 SD/SD, P<0.001), slower processing speed (-0.118 +/- 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 +/- 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.","Age Factors;Aged;Aged, 80 and over;Aorta/ physiopathology;Blood Flow Velocity/ physiology;Blood Pressure/ physiology;Brain/blood supply/pathology/ physiopathology;Cardiovascular Diseases/pathology/physiopathology;Carotid Arteries/ physiopathology;Female;Gene-Environment Interaction;Humans;Iceland;Male;Prospective Studies;Pulsatile Flow/ physiology;Risk Factors;Vascular Stiffness/ physiology","Mitchell, G. F.;van Buchem, M. A.;Sigurdsson, S.;Gotal, J. D.;Jonsdottir, M. K.;Kjartansson, O.;Garcia, M.;Aspelund, T.;Harris, T. B.;Gudnason, V.;Launer, L. J.",2011,Nov,10.1093/brain/awr253,0,
2473,"The measurement of R2, R2* and R2' in HIV-infected patients using the prime sequence as a measure of brain iron deposition","Brain iron deposition was assessed at 1.5 T in the caudate nucleus, globus pallidus and frontal and parieto-occipital white matter in 28 human immunodeficiency virus (HIV)-infected patients and 15 control subjects with a new Partially Refocussed Interleaved Multi-Echo sequence by measuring 1/T2, 1/T2* and 1/T2' (i.e., R2, R2* and R2'). There were significant differences in the R2 and R2* of the caudate nucleus (p < 0.0001 and p < 0.05) and the R2, R2* and R2' of the globus pallidus (p < 0.01, p < 0.005 and p < 0.05) in HIV-infected patients compared to control subjects. There was a trend for higher values of R2, R2* and R2' in the globus pallidus and caudate nucleus in HIV-infected patients with later stage HIV disease. These results suggest that there is greater iron deposition in the basal ganglia of HIV-infected patients compared with control subjects, with a predilection for the globus pallidus. The relationship between iron deposition in the brain and various parameters of severity of HIV infection remains uncertain.",AIDS Dementia Complex/*metabolism/pathology;Adult;Basal Ganglia/metabolism/pathology;Brain/*metabolism/pathology;CD4 Lymphocyte Count;Caudate Nucleus/metabolism/pathology;Female;Globus Pallidus/metabolism/pathology;Humans;Iron/*metabolism;Magnetic Resonance Imaging;Male,"Miszkiel, K. A.;Paley, M. N.;Wilkinson, I. D.;Hall-Craggs, M. A.;Ordidge, R.;Kendall, B. E.;Miller, R. F.;Harrison, M. J.",1997,,,0,
2474,"Vitamin B12 deficiency neurological syndromes: a clinical, MRI and electrodiagnostic study","BACKGROUND: Vegetarianism is an important cause of vitamin B12 deficiency, especially in countries like India. We managed 17 patients with neurological syndrome due to vitamin B12 deficiency in a tertiary care referral teaching hospital which caters to relatively affluent population. AIM: To evaluate neurophysiological and MRI changes in patients presenting with vitamin B12 deficiency neurological syndrome and interpret these is the light of reported autopsy findings. SETTING: Tertiary care referral teaching hospital. METHODS: Patients with vitamin B12 deficiency neurological syndrome diagnosed by low serum vitamin B12 and/or megaloblastic bone marrow were subjected to clinical evaluation and spinal MRI. The neurophysiological tests included nerve conduction studies, tibial somatosensory evoked potential (SEP), motor evoked potential (MEP) and visual evoked potential (VEP) studies. The recovery was defined on the basis of 6 months Barthel Index score into complete, partial or poor. RESULTS: There were 17 patients with vitamin B12 deficiency neurological syndrome, 3 were females and 12 lactovegetarian. The clinical syndrome was that of myelopathy in 8, myeloneuropathy in 5, dementia myelopathy in 3 and neuropathy in 1 patient. All the patients had impaired joint position and vibration sensation in the lower limbs and 4 had in upper limbs as well. Lower limbs were spastic in 13 and upper limbs in 2 patients. Spinal MRI revealed T2 hyperintensity in cervicodorsal region in 6 and cord atrophy in 3 patients. Sural nerve conduction was abnormal in 8 and peroneal conduction in 5 patients. In one patient all sensory nerve conductions were unrecordable but motor conductions were normal. Tibial SEP was abnormal in 12 out of 15 and lower limb MEP in 8 out of 12 patients. P100 latency of VEP was prolonged in 7 out of 13 patients. Right to left asymmetry was present in tibial SEP in 4 and VEP in 2 patients. At 6 months followup 2 patients improved completely, 7 partially and 3 had poor recovery. Clinical recovery correlated with MEP but not with SEP or MRI changes. CONCLUSION: The evoked potential and MRI changes in vitamin B12 deficiency neurological syndrome are consistent with focal demyelination of white matter in spinal cord and optic nerve. Myelopathic presentation is commoner and SEP is more frequently abnormal. The outcome at 6 months correlated with MEP changes.",Adolescent;Adult;Aged;*Electromyography;Evoked Potentials/physiology;Female;Follow-Up Studies;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Nervous System Diseases/*etiology/pathology/*physiopathology;Neural Conduction/physiology;*Neurophysiology;Outcome Assessment (Health Care);Recovery of Function/physiology;Severity of Illness Index;Syndrome;Time Factors;Vitamin B 12 Deficiency/*complications/pathology/*physiopathology,"Misra, U. K.;Kalita, J.;Das, A.",2003,Jan-Feb,,0,
2475,"Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: results from ADNI","High-dimensional pattern classification was applied to baseline and multiple follow-up MRI scans of the Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI), in order to investigate the potential of predicting short-term conversion to Alzheimer's Disease (AD) on an individual basis. MCI participants that converted to AD (average follow-up 15 months) displayed significantly lower volumes in a number of grey matter (GM) regions, as well as in the white matter (WM). They also displayed more pronounced periventricular small-vessel pathology, as well as an increased rate of increase of such pathology. Individual person analysis was performed using a pattern classifier previously constructed from AD patients and cognitively normal (CN) individuals to yield an abnormality score that is positive for AD-like brains and negative otherwise. The abnormality scores measured from MCI non-converters (MCI-NC) followed a bimodal distribution, reflecting the heterogeneity of this group, whereas they were positive in almost all MCI converters (MCI-C), indicating extensive patterns of AD-like brain atrophy in almost all MCI-C. Both MCI subgroups had similar MMSE scores at baseline. A more specialized classifier constructed to differentiate converters from non-converters based on their baseline scans provided good classification accuracy reaching 81.5%, evaluated via cross-validation. These pattern classification schemes, which distill spatial patterns of atrophy to a single abnormality score, offer promise as biomarkers of AD and as predictors of subsequent clinical progression, on an individual patient basis.","Aged;Aged, 80 and over;*Algorithms;Alzheimer Disease/*pathology;Atrophy/pathology;Brain/*pathology;Cognition Disorders/*pathology;Disease Progression;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/*methods;Longitudinal Studies;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Pattern Recognition, Automated/*methods;Prognosis;Reproducibility of Results;Sensitivity and Specificity","Misra, C.;Fan, Y.;Davatzikos, C.",2009,Feb 15,10.1016/j.neuroimage.2008.10.031,0,
2476,Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the Era of Volumetric MR Imaging,"Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient. Volumetric segmentation of global gray matter, white matter, ventricles, and hippocampi was performed by using software. These measures were tested by using multivariable logistic regression models to determine which combination of metrics is most accurate in diagnosis. Results The model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area under the curve of 0.96 in differentiating patients with NPH from patients without NPH (ie, Alzheimer disease and healthy control). The regression model that used volumetric predictors of gray matter and white matter was 94.3% accurate. Conclusion CA and EI may serve as a screening tool to help the radiologist differentiate patients with NPH from patients without NPH, which would allow for designation of patients for further volumetric assessment. ((c)) RSNA, 2017.","Adult;Aged;Aged, 80 and over;Brain/diagnostic imaging/pathology;Female;Humans;Hydrocephalus, Normal Pressure/ diagnostic imaging/pathology;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Prospective Studies","Miskin, N.;Patel, H.;Franceschi, A. M.;Ades-Aron, B.;Le, A.;Damadian, B. E.;Stanton, C.;Serulle, Y.;Golomb, J.;Gonen, O.;Rusinek, H.;George, A. E.;Alzheimer's Disease Neuroimaging, Initiative",2017,Oct,,0,
2477,Differentiating between visual hallucination-free dementia with Lewy bodies and corticobasal syndrome on the basis of neuropsychology and perfusion single-photon emission computed tomography,"INTRODUCTION: Dementia with Lewy bodies (DLB) and Corticobasal Syndrome (CBS) are atypical parkinsonian disorders with fronto-subcortical and posterior cognitive dysfunction as common features. While visual hallucinations are a good predictor of Lewy body pathology and are rare in CBS, they are not exhibited in all cases of DLB. Given the clinical overlap between these disorders, neuropsychological and imaging markers may aid in distinguishing these entities. METHODS: Prospectively recruited case-control cohorts of CBS (n =31) and visual hallucination-free DLB (n =30), completed neuropsychological and neuropsychiatric measures as well as brain perfusion single-photon emission computed tomography and structural magnetic resonance imaging (MRI). Perfusion data were available for forty-two controls. Behavioural, perfusion, and cortical volume and thickness measures were compared between the groups to identify features that serve to differentiate them. RESULTS: The Lewy body with no hallucinations group performed more poorly on measures of episodic memory compared to the corticobasal group, including the delayed and cued recall portions of the California Verbal Learning Test (F (1, 42) =23.1, P <0.001 and F (1, 42) =14.0, P =0.001 respectively) and the delayed visual reproduction of the Wechsler Memory Scale-Revised (F (1, 36) =9.7, P =0.004). The Lewy body group also demonstrated reduced perfusion in the left occipital pole compared to the corticobasal group (F (1,57) =7.4, P =0.009). At autopsy, the Lewy body cases all demonstrated mixed dementia with Lewy bodies, Alzheimer's disease and small vessel arteriosclerosis, while the corticobasal cases demonstrated classical corticobasal degeneration in five, dementia with agyrophilic grains + corticobasal degeneration + cerebral amyloid angiopathy in one, Progressive Supranuclear Palsy in two, and Frontotemporal Lobar Degeneration-Ubiquitin/TAR DNA-binding protein 43 proteinopathy in one. MRI measures were not significantly different between the patient groups. CONCLUSIONS: Reduced perfusion in the left occipital region and worse episodic memory performance may help to distinguish between DLB cases who have never manifested with visual hallucinations and CBS at earlier stages of the disease. Development of reliable neuropsychological and imaging markers that improve diagnostic accuracy will become increasingly important as disease modifying therapies become available.",,"Misch, M. R.;Mitchell, S.;Francis, P. L.;Sherborn, K.;Meradje, K.;McNeely, A. A.;Honjo, K.;Zhao, J.;Scott, C. J.;Caldwell, C. B.;Ehrlich, L.;Shammi, P.;MacIntosh, B. J.;Bilbao, J. M.;Lang, A. E.;Black, S. E.;Masellis, M.",2014,,10.1186/s13195-014-0071-4,0,
2478,Clinical correlates of white-matter changes on magnetic resonance imaging scans of the brain,"We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects.","Aged;Brain/ pathology;Brain Diseases/ diagnosis/psychology/radiography;Cerebral Ventricles/pathology;Cognition;Dementia, Multi-Infarct/pathology/radiography;Female;Humans;Magnetic Resonance Imaging;Male;Prospective Studies","Mirsen, T. R.;Lee, D. H.;Wong, C. J.;Diaz, J. F.;Fox, A. J.;Hachinski, V. C.;Merskey, H.",1991,Oct,,0,
2479,V1-V2-V3-V4 T wave inversion: Left or right ventricle?,"An 84-year-old woman, affected by Alzheimer's disease, presented to the emergency department with intense dyspnoea. Since ECG was showing T wave inversion in anterior leads and troponin-T was high, the patient was admitted to our unit with a diagnosis of anterior non-ST elevation myocardial infarction. However, the patient's medical history and a further review of the ECG led us to suspect a pulmonary embolism (PE) as a possible differential clinical diagnosis. We tested this alternative hypothesis: echocardiography as well as contrast-enhanced CT scan confirmed the diagnosis of PE. We describe these misleading ECG findings together with a brief discussion of electrocardiographical changes in pulmonary embolism. Copyright 2013 BMJ Publishing Group. All rights reserved.",anticoagulant agent;troponin T;aged;Alzheimer disease;article;case report;computer assisted tomography;contrast enhancement;differential diagnosis;Doppler echography;dyspnea;echocardiography;electrocardiography;emergency ward;female;heart left ventricle;heart right ventricle;hospital admission;hospital discharge;human;lung embolism;medical history;non ST segment elevation myocardial infarction;patient referral;prescription;priority journal;T wave inversion;treatment outcome,"Mirijello, A.;Pola, R.;Saviano, L.;Landolfi, R.",2013,,,0,
2480,CADASIL presenting with a movement disorder: A clinical study of a Chilean kindred,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular disease that usually begins with migraine, followed by repeated strokes and progressive dementia. We describe an unusual clinical presentation of this condition in members of a Chilean family with an established NOTCH3 mutation. We report early clinical, neuropsychological, transcranial ultrasound, magnetic resonance imaging (MRI), cerebral blood flow, and skin biopsy findings on these patients. Of the patients, 2 presented with facial dystonia, 1 of whom had abnormal single photon emission computed tomography and transcranial ultrasound studies after normal brain MRI scans. Our report emphasizes that CADASIL must be considered in the study of patients with secondary dystonia. © 2006 Movement Disorder Society.",,"Miranda, M.;Dichgans, M.;Slachevsky, A.;Urbina, F.;Mena, I.;Venegas, P.;Galvez, M.",2006,July,,0,
2481,Structural brain changes and cognition in relation to markers of vascular dysfunction,"The aim was to investigate the relationship between blood markers of vascular dysfunction with brain microstructural changes and cognition. Eighty-six participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. We assessed correlations of blood levels of inflammatory biomarkers (C-reactive protein [CRP] and resistin) and fibrinolysis inhibitors (plasminogen activator inhibitor-1 [PAI-1] and A-lipoprotein (Lp (a)) with fractional anisotropy (FA) measurements of diffusion tensor images (DTI), regional gray matter (GM) volumes and performance in several cognitive domains. Increasing levels of C-reactive protein and PAI-1 levels were associated with white matter (WM) integrity loss in corticosubcortical pathways and association fibers of frontal and temporal lobes, independently of age, sex and vascular risk factors. PAI-1 was also related to lower speed and visuomotor/coordination. None of the biomarkers were related to gray matter volume changes. Our findings suggest that inflammation and dysregulation of the fibrynolitic system may be involved in the pathological mechanisms underlying the WM damage seen in cerebrovascular disease and subsequent cognitive impairment.","Aged;Aging/blood/pathology;Brain/blood supply/ pathology/physiopathology;Cerebral Arteries/physiopathology;Cerebrovascular Disorders/ blood/epidemiology/ physiopathology;Cognition Disorders/ blood/epidemiology/ pathology;Comorbidity/trends;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests;Psychomotor Performance/physiology","Miralbell, J.;Soriano, J. J.;Spulber, G.;Lopez-Cancio, E.;Arenillas, J. F.;Bargallo, N.;Galan, A.;Barrios, M. T.;Caceres, C.;Alzamora, M. T.;Pera, G.;Kivipelto, M.;Wahlund, L. O.;Davalos, A.;Mataro, M.",2012,May,10.1016/j.neurobiolaging.2011.09.020,0,
2482,Anatomic standardization: linear scaling and nonlinear warping of functional brain images,"An automated method was proposed for anatomic standardization of PET scans in three dimensions, which enabled objective intersubject and cross-group comparisons of functional brain images. METHODS: The method involved linear scaling to correct an individual brain size and nonlinear warping to minimize regional anatomic variations among subjects. In the linear-scaling step, the anteroposterior length and width of the brain were measured on the PET images, and the brain height was estimated by a contour-matching procedure using the midsagittal plane. In the nonlinear warping step, individual gray matter locations were matched with those of a standard brain by maximizing correlation coefficients of regional profile curves determined between predefined stretching centers (predominantly in white matter) and the gray matter landmarks. RESULTS: The accuracy of the brain height estimation was compared with skull x-ray estimations, showing comparable accuracy and better reproducibility. Linear-scaling and nonlinear warping methods were validated using [18F]fluorodeoxyglucose and [15O]water images. Regional anatomic variability on the glucose images was reduced markedly. The statistical significance of activation foci in paired water images was improved in both vibratory and visual activation paradigms. A group versus group comparison following the proposed anatomic standardization revealed highly significant glucose metabolic alterations in the brains of patients with Alzheimer's disease compared with those of a normal control group. CONCLUSION: These results suggested that the method is well suited to both research and clinical settings and can facilitate pixel-by-pixel comparisons of PET images.","Algorithms;Alzheimer Disease/radionuclide imaging;Brain/ anatomy & histology/metabolism/ radionuclide imaging;Deoxyglucose/analogs & derivatives;Fluorine Radioisotopes;Fluorodeoxyglucose F18;Glucose/metabolism;Humans;Oxygen Radioisotopes;Reference Standards;Tomography, Emission-Computed/ standards;Water","Minoshima, S.;Koeppe, R. A.;Frey, K. A.;Kuhl, D. E.",1994,Sep,,0,
2483,Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke,"Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 +/- 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.","Age Factors;Aged;Alzheimer Disease/diagnosis;Brain/*radiography;Cross-Sectional Studies;Dementia/pathology/prevention & control;Diabetes Complications/diagnosis;Female;Humans;Hyperlipidemias/complications;Hypertension/complications;Interviews as Topic;Male;Middle Aged;Odds Ratio;Periodontal Diseases/complications/*diagnosis;Predictive Value of Tests;Risk Factors;Stroke/pathology/prevention & control;Tomography, X-Ray Computed;Tooth Loss;Alzheimer Disease;Dementia;Dental Caries;Health Promotion;Leukoencephalopathy;Periodontitis;Preventive Health Service","Minn, Y. K.;Suk, S. H.;Park, H.;Cheong, J. S.;Yang, H.;Lee, S.;Do, S. Y.;Kang, J. S.",2013,Jun,10.3346/jkms.2013.28.6.929,0,
2484,Osteoporosis as an independent risk factor for silent brain infarction and white matter changes in men and women: the PRESENT project,"SUMMARY: Previous studies have not demonstrated a relationship between osteoporosis and cerebral infarction in the community, especially in men. We found that osteoporosis may be an independent risk factor for brain white matter change/silent infarction in men, as well as in women. PURPOSE: We aimed to study the relationship between low bone mineral density (BMD) and brain white matter changes and/or silent infarcts (WMC/SI). METHODS: This was a community-based, cross-sectional study supported by the regional government. Bone mineral density measurements and brain computed tomography were performed in 646 stroke- and dementia-free subjects (aged 50-75 years). RESULTS: After adjustment for age, hypertension, diabetes mellitus, dyslipidemia, and current smoking status, the odds ratio (OR) of risk for WMC and/or SI was 1.8 in the osteopenia group (95 % confidence interval [CI] 1.15-2.77; P = 0.01) and 2.2 in the osteoporosis group (95 % CI 1.42-3.55; P < 0.001). Among men, the OR was 1.8 (95 % CI 0.72-4.62; P = 0.21) and 3.8 (95 % CI 1.63-8.86; P = 0.002), and in women, the OR was 1.9 (95 % CI 1.15-2.78; P = 0.010) and 2.2 (95 % CI 1.42-3.55; P = 0.001), respectively. CONCLUSIONS: Severe bone mass loss may be an independent risk factor for brain WMC/SI in men and women. Low BMD may cause brain WMC/SI in the step that leads to stroke. Although there are well-designed studies on the prevention of cerebral infarction in patients with brain WMC/SI, a specific prevention method, such as aspirin, should be used for patients with low BMD who have WMC/SI. Screening for low BMD as an independent vascular risk factor in healthy subjects may be required to prevent stroke.","Absorptiometry, Photon/methods;Aged;Bone Density/physiology;Brain Infarction/epidemiology/*etiology/physiopathology/radiography;Cross-Sectional Studies;Female;Humans;Leukoencephalopathies/epidemiology/*etiology/physiopathology/radiography;Male;Middle Aged;Osteoporosis/*complications/epidemiology/physiopathology;Republic of Korea/epidemiology;Risk Factors;Tomography, X-Ray Computed","Minn, Y. K.;Suk, S. H.;Do, S. Y.",2014,Oct,10.1007/s00198-014-2785-3,0,
2485,Higher skeletal muscle mass may protect against ischemic stroke in community-dwelling adults without stroke and dementia: The PRESENT project,"BACKGROUND: It is well known that a low skeletal muscle mass (SMM) is associated with stroke. However, it is unknown whether increasing muscle mass can prevent stroke. METHODS: This community-based cross-sectional study was supported by the regional government. SMM measurements and brain computed tomography was performed in 722 stroke-free and dementia-free subjects (aged 50-75 years). Subjects were divided into quartiles (Q) by SMM, checked using the bioelectrical impedance analysis method (InBody 770, InBody, Seoul, Korea). Odds ratios (ORs) of brain white matter changes/silent infarction (WMC/SI) were calculated. The subjects were then divided into two groups by sex and evaluated. RESULTS: In the analysis of the four groups, the unadjusted ORs of Q2-Q4 were 0.616 (95% confidence interval [CI], 0.372-1.022; P = 0.061), 0.290 (CI, 0.159-0.530; P < 0.001), and 0.209 (CI, 0.108-0.403; P < 0.001) for the risk of WMC/SI. Adjusted ORs for age, hypertension, diabetes mellitus, education, hypercholesterolemia, and smoking were 0.994 (CI, 0.513-1.740; P = 0.085), 0.669 (CI, 0.329-1.362; P = 0.268), and 0.464 (CI, 0.219-0.984; P = 0.045). In the two-group (dichotomized) analysis, the unadjusted OR for the higher muscle mass groups (Q3 + Q4) was 0.313 (CI, 0.200-0.491; P < 0.001). The adjusted OR was 0.577 (CI, 0.340-0.979; P = 0.042). Considering sex, the adjusted OR were 0.351 (CI, 0.141-0.869; P = 0.024) in men and 0.771 (CI, 0.391-1.519; P = 0.452) in women. CONCLUSIONS: Our findings suggest that increased SMM may protect against WMC/SI, especially in men.",Bioelectrical impedance analysis (BIA);Body composition;Risk factor;Sarcopenia;Skeletal muscle mass;Stroke,"Minn, Y. K.;Suk, S. H.",2017,Feb 03,,0,
2486,Integrated cortical structural marker for Alzheimer's disease,"In this article, we propose an approach to integrate cortical morphology measures for improving the discrimination of individuals with and without very mild Alzheimer's disease (AD). FreeSurfer was applied to scans collected from 83 participants with very mild AD and 124 cognitively normal individuals. We generated cortex thickness, white matter convexity (aka ""sulcal depth""), and white matter surface metric distortion measures on a normalized surface atlas in this first study to integrate high resolution gray matter thickness and white matter surface geometric measures in identifying very mild AD. Principal component analysis was applied to each individual structural measure to generate eigenvectors. Discrimination power based on individual and combined measures are compared, based on stepwise logistic regression and 10-fold cross-validation. Global AD likelihood index and surface-based likelihood maps were also generated. Our results show complementary patterns on the cortical surface between thickness, which reflects gray matter atrophy, convexity, which reflects white matter sulcal depth changes and metric distortion, which reflects white matter surface area changes. The classifier integrating all 3 types of surface measures significantly improved classification performance compared with classification based on single measures. The principal component analysis-based approach provides a framework for achieving high discrimination power by integrating high-dimensional data, and this method could be very powerful in future studies for early diagnosis of diseases that are known to be associated with abnormal gyral and sulcal patterns.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*pathology;Atrophy;Biomarkers;Cerebral Cortex/*pathology;Female;Gray Matter/pathology;Humans;Magnetic Resonance Imaging/*methods;Male;Neuroimaging/*methods;White Matter/pathology;Classification;Convexity;Cortical geometry;Cortical thickness;Metric distortion;Neuroimaging","Ming, J.;Harms, M. P.;Morris, J. C.;Beg, M. F.;Wang, L.",2015,Jan,10.1016/j.neurobiolaging.2014.03.042,0,
2487,"Subjective memory complaints, white-matter int lesions, depressive symptoms, and cognition in elderly patients","Objectives: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. Methods: This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. Results: Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. Conclusions: Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression. © 2005 American Association for Geriatric Psychiatry.",adult;age;aged;aging;article;cognitive defect;controlled study;correlation coefficient;daily life activity;depression;disease severity;education;female;gender;geriatric disorder;human;major clinical study;male;Memory Complaint Questionnaire;memory disorder;Mini Mental State Examination;mood;multivariate logistic regression analysis;neuropsychological test;nuclear magnetic resonance imaging;questionnaire;white matter,"Minett, T. S. C.;Dean, J. L.;Firbank, M.;English, P.;O'Brien, J. T.",2005,,,0,
2488,"Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients","OBJECTIVES: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. METHODS: This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. RESULTS: Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. CONCLUSIONS: Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression.","Activities of Daily Living/classification;Aged;Alzheimer Disease/*diagnosis/epidemiology;Amnesia/*diagnosis/epidemiology;Brain/*pathology;Cognition Disorders/*diagnosis/epidemiology;Cross-Sectional Studies;Demyelinating Diseases/*diagnosis/epidemiology;Depression/*diagnosis/epidemiology;Diagnosis, Differential;Female;Humans;*Image Enhancement;*Image Processing, Computer-Assisted;*Magnetic Resonance Imaging;Male;Middle Aged;Reference Values;Statistics as Topic","Minett, T. S.;Dean, J. L.;Firbank, M.;English, P.;O'Brien, J. T.",2005,Aug,10.1176/appi.ajgp.13.8.665,0,
2489,Cerebral ventricles are smaller in Hispanic than non-Hispanic patients with Alzheimer's disease,"MRI scans were compared between 71 Hispanic and 73 white non-Hispanic patients with National Institute of Neurological Disorders and Stroke probable AD. Analysis of covariance controlled for age, sex, education, and Mini-Mental State Examination scores indicated that ventricular size was smaller in Hispanic than white non-Hispanic patients (p = 0.0003). There was no difference in cortical atrophy and T2-weighted white matter hyperintense signals between groups.",Aged;Alzheimer Disease/*ethnology/*pathology;Cerebral Ventricles/*pathology;Female;*Hispanic Americans;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Minagar, A.;Sevush, S.;Bertran, A.",2000,Aug 8,,0,
2490,Effect of compound danshen on neural function defect and free radicals in patients with cerebral infarction,"Background: Various etiological mechanisms are involved in cerebral infarction. Both free radicals and lipid peroxidation participate in the atherosclerosis and damage of neural cells after cerebral ischemia. Compound danshen (Radix Salviae Miltiorrhizae) is a common prescribed Chinese herb, acting on activating blood circulation and removing stasis for cerebral infarction and coronary heart disease, but its mechanism has been unknown in many aspects. Objective: To observe the effect of compound danshen on neural function defect and free radicals in patients with cerebral infarction so as to probe into its possible mechanisms. Design: A randomized controlled trial. Setting: Neurological Internal Department of a hospital affiliated to one university. Participants: Totally 538 inpatients were collected in Neurological Internal Department of First Hospital affiliated to Jinzhou Medical College from February to December 2002, their diagnosis compiled with ""Diagnostic Keys on Every Type Cerebral Vascular Disorders"" adopted on the 4th National Academic Meeting on Cerebral Vascular Disorders, and determined by cerebral CT scan. All of those were the first attack of atherosclerosis cerebral infarction in 72 hours. The patients with cardiac infarction, heart failure, auricular fibrillation, insufficiency of liver and kidney function, hemorrhage of digestive tract, vascular dementia and bulbar paralysis and the patients who could not be well cooperated were not included. A total of 68 patients compiled with the standards, of which, 38 patients were male and 30 patients female, aged varied from 52 to 78 years, at the average of (64.62 ± 5.80) years. The patients selected were randomized into study group and the control by lot-drawing method according to the hospitalized sequence and volunteer principle of the control. Methods: The basic treatment was same in two groups. In study group, compound danshen injection was added together with physiological saline 250 mL for intra-venous drip, once daily, continuous 14 days made one course. In the control, thrombosis removing injection 15 mL was added together with physiological saline 250 mL for intra-venous drip, once daily, continuous 14 days made one course. Main outcome measures: 1 Evaluation on defect severity of clinical neural function; 2 Evaluation of clinical therapeutic effects; 3 Level of serum lipoperoxide(LPO) and activity of superoxide dismutase (SOD). Results: Statistical differences presented in declined scores of severity of neural function defect after treatment in two groups compared with their own controls (in study group: 28.62 ± 6.76 vs 13.84 ± 8.16; in the control: 28.58 ± 7.05 vs 21.52 ± 8.24, t = 8.134, t = 3.796 respectively, P < 0.001). The score in study group was declined more obviously compared with the control after treatment, indicating very significant difference (t = 3.861, P < 0.001). The effective rate of compound danshen injection was 88.24% in treatment of cerebral infarction, which significantly superior to that in the control (67.65% ) (χ2=4.19, P < 0.05). Compound danshen remarkably reduced serum LPO level [(8.69 ± 1.28) nmol/L vs (5.86 ± 1.42) nmol/L, t = 8.628, P < 0.001] and statistical differences presented compared with the result in the control after treatment [(5.86, ± 1.42) amol/L vs (8.56 ± 0.95) nmol/L, t = 9.125, P < 0.001]. Simultaneously, SOD activity in serum was significantly increased, [(26.25 ± 4.64) mkat/g vs (30.01 ± 3.87) mkat/g, t = 3.629, P < 0.001] indicating statistical differences compared with the result in the control after treatment [(30.01 ± 3.87) mkat/g vs (26.33 ± 4.14) mkat/g, t = 3.778, P < 0.001]. Conclusion: Compound danshen improves significantly neural function defect in patients with cerebral infarction, with definite therapeutic effects on the treatment. It can reduce serum LPO content and increase serum SOD activity in patients with cerebral infarction. It is predicted that removing free radicals and anti-lipid peroxidation damage is probably one of the important mechanisms of it, which pr vides a further theoretic evidence for the treatment of cerebral infarction clinically.",anticoagulant agent;free radical;lipid peroxide;Salvia miltiorrhiza extract;sodium chloride;superoxide dismutase;adult;aged;article;brain atherosclerosis;brain infarction;clinical trial;computer assisted tomography;controlled study;disease severity;drug efficacy;drug mechanism;enzyme activity;female;human;lipid blood level;major clinical study;male;nerve function;randomized controlled trial;Salvia miltiorrhiza;statistical significance,"Min, L. Q.;Wang, X. J.;Yang, L.;Ma, W. Y.;Yuan, J.;Liu, X. W.",2005,,,0,
2491,Lateralized occipital degeneration in posterior cortical atrophy predicts visual field deficits,"BACKGROUND: Posterior cortical atrophy (PCA), the visual variant of Alzheimer's disease, leads to high-level visual deficits such as alexia or agnosia. Visual field deficits have also been identified, but often inconsistently reported. Little is known about the pattern of visual field deficits or the underlying cortical changes leading to this visual loss. METHODS: Multi-modal magnetic resonance imaging was used to investigate differences in gray matter volume, cortical thickness, white matter microstructure and functional activity in patients with PCA compared to age-matched controls. Additional analyses investigated hemispheric asymmetries in these metrics according to the visual field most affected by the disease. RESULTS: Analysis of structural data indicated considerable loss of gray matter in the occipital and parietal cortices, lateralized to the hemisphere contralateral to the visual loss. This lateralized pattern of gray matter loss was also evident in the hippocampus and parahippocampal gyrus. Diffusion-weighted imaging showed considerable effects of PCA on white matter microstructure in the occipital cortex, and in the corpus callosum. The change in white matter was only lateralized in the occipital lobe, however, with greatest change in the optic radiation contralateral to the visual field deficit. Indeed, there was a significant correlation between the laterality of the optic radiation microstructure and visual field loss. CONCLUSIONS: Detailed brain imaging shows that the asymmetric visual field deficits in patients with PCA reflect the pattern of degeneration of both white and gray matter in the occipital lobe. Understanding the nature of both visual field deficits and the neurodegenerative brain changes in PCA may improve diagnosis and understanding of this disease.",Hemianopia;Magnetic resonance imaging;Occipital lobe;Posterior cortical atrophy;Visual dysfunction,"Millington, R. S.;James-Galton, M.;Maia Da Silva, M. N.;Plant, G. T.;Bridge, H.",2017,,,0,
2492,Multimodality Review of Amyloid-related Diseases of the Central Nervous System,"Amyloid-beta (Abeta) is ubiquitous in the central nervous system (CNS), but pathologic accumulation of Abeta results in four distinct neurologic disorders that affect middle-aged and elderly adults, with diverse clinical presentations ranging from chronic debilitating dementia to acute life-threatening intracranial hemorrhage. The characteristic imaging patterns of Abeta-related CNS diseases reflect the pathophysiology of Abeta deposition in the CNS. Abeta is recognized as a key component in the neuronal damage that characterizes the pathophysiology of Alzheimer disease, the most common form of dementia. Targeted molecular imaging shows pathologic accumulation of Abeta and tau protein, and fluorine 18 fluorodeoxyglucose positron emission tomography and anatomic imaging allow differentiation of typical patterns of neuronal dysfunction and loss in patients with Alzheimer disease from those seen in patients with other types of dementia. Cerebral amyloid angiopathy (CAA) is an important cause of cognitive impairment and spontaneous intracerebral hemorrhage in the elderly. Hemorrhage and white matter injury seen at imaging reflect vascular damage caused by the accumulation of Abeta in vessel walls. The rare forms of inflammatory angiopathy attributed to Abeta, Abeta-related angiitis and CAA-related inflammation, cause debilitating neurologic symptoms that improve with corticosteroid therapy. Imaging shows marked subcortical and cortical inflammation due to perivascular inflammation, which is incited by vascular Abeta accumulation. In the rarest of the four disorders, cerebral amyloidoma, the macroscopic accumulation of Abeta mimics the imaging appearance of tumors. Knowledge of the imaging patterns and pathophysiology is essential for accurate diagnosis of Abeta-related diseases of the CNS. ((c))RSNA, 2016.",,"Miller-Thomas, M. M.;Sipe, A. L.;Benzinger, T. L.;McConathy, J.;Connolly, S.;Schwetye, K. E.",2016,Jul-Aug,10.1148/rg.2016150172,0,
2493,Reduced glutathione is highly expressed in white matter and neurons in the unperturbed mouse brain--implications for oxidative stress associated with neurodegeneration,"Oxidative stress is implicated in the pathogenesis of many neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. The depletion of glutathione (GSH) a powerful antioxidant renders cells particularly vulnerable to oxidative stress. Isolated neuronal and glial cell culture studies suggest that glia rather than neurons have greatest reserves of GSH, implying that neurons are most sensitive to oxidative stress. However, pathological in vivo studies suggest that GSH associated enzymes are elevated in neurons rather than astrocytes. The active, reduced form of GSH is rapidly degraded thus making it difficult to identify the location of GSH in post-mortem tissue. Therefore, to determine whether GSH is more highly expressed in neurons or astrocytes we perfused mouse brains with a solution containing NEM which reacts with the sulfhydryl group of GSH, thus locking the active form in situ, prior to immunostaining with an anti-GS-NEM antibody. We obtained brightfield and fluorescent digital images of sections stained with DAPI and antibodies directed against GS-NEM, glial fibrillary acidic protein (GFAP) in regions containing the hippocampus, striatum, frontal cortex, midbrain nuclei, cerebellum and reticular formation neurons. GSH was most abundant in neurons and white matter in all brain regions, and only in occasional astrocytes lining the third and fourth ventricles. High levels of GSH in neurons and white matter, suggests astrocytes rather than neurons may be particularly vulnerable to oxidative stress.",Animals;Astrocytes/ metabolism;Brain/ metabolism;Cerebellum/metabolism;Cerebral Ventricles/metabolism;Fluorescent Antibody Technique;Glial Fibrillary Acidic Protein/metabolism;Glutathione/ metabolism;Hippocampus/metabolism;Immunohistochemistry;Mice;Myelin Sheath/ metabolism;Nerve Degeneration;Neurons/ metabolism;Oxidative Stress;Photomicrography;Reticular Formation/metabolism,"Miller, V. M.;Lawrence, D. A.;Mondal, T. K.;Seegal, R. F.",2009,Jun 18,10.1016/j.brainres.2009.04.029,0,
2494,Labeled cortical mantle distance maps of the cingulate quantify differences between dementia of the Alzheimer type and healthy aging,"The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian segmentation of the cortex and gray matter/white matter (GM/WM) isosurface generation, tissue compartments were labeled into gray, white, and cerebrospinal fluid as a function of distance from the GM/WM isosurface. Cortical mantle distance maps are generated profiling the GM volume and cortical mantle distribution as a function of distance from the cortical surface. Probabilistic tests based on generalizations of Wilcoxon-Mann-Whitney tests were applied to quantify cortical mantle distribution changes with normal and abnormal aging. We find no significant change between young controls and healthy aging as measured by the GM volume and cortical mantle distribution as a function of distance in both anterior and posterior regions of the cingulate. Significant progression of GM loss is seen in the very mild DAT and mild DAT groups in all areas of the cingulate. Posterior regions show both GM volume loss as well as significant cortical mantle distribution decrease with the onset of mild DAT. The ""shape of the cortical mantle"" as measured by the cortical mantle distance profiles manifests a pronounced increase in variability with mild DAT.","Adult;Age Factors;Aged;Aging;Alzheimer Disease/*metabolism/*pathology;Bayes Theorem;Brain/pathology;*Brain Mapping;Cerebral Cortex/pathology;Dementia/pathology;Female;Gyrus Cinguli/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Models, Statistical;Stochastic Processes","Miller, M. I.;Hosakere, M.;Barker, A. R.;Priebe, C. E.;Lee, N.;Ratnanather, J. T.;Wang, L.;Gado, M.;Morris, J. C.;Csernansky, J. G.",2003,Dec 9,10.1073/pnas.2136624100,0,
2495,MRI High-Intensity Signals in Late-Life Depression and Alzheimer's Disease: A Comparison of Subjects Without Major Vascular Risk Factors,"The authors examined periventricular white matter, deep white matter, and subcortical magnetic resonance imaging (MRI) high-intensity signals in subjects with late-life depression, probable Alzheimer's disease (DAT), and healthy, age-matched controls. All subjects were healthy and free of major vascular risk factors, including hypertension. MRIs were performed using a 1.5-tesla GE Signa scanner. T2 and proton-density-weighted images were analyzed by a neuroradiologist blind to the clinical status of all subjects. There were no statistically significant differences on any of the MRI indices between the groups studied. These data demonstrate that late-life depression, like DAT, in the absence of major vascular risk factors, is not associated with a significant increase in MRI high-intensity signals when compared to healthy, control subjects.",,"Miller, D. S.;Kumar, A.;Yousem, D. M.;Gottlieb, G. L.",1994,Autumn,,0,
2496,MRI high-intensity signals in late-life depression and Alzheimer disease: A comparison of subjects without major vascular risk factors,"The authors examined periventricular white matter, deep white matter, and subcortical magnetic resonance imaging (MRI) high-intensity signals in subjects with late-life depression, probable Alzheimer's disease (DAT), and healthy, age-matched controls. All subjects were healthy and free of major vascular risk factors, including hypertension. MRIs were performed using a 1.5-tesla GE Signa scanner. T(2) and proton-density-weighted images were analyzed by a neuroradiologist blind to the clinical status of all subjects. There were no statistically significant differences on any of the MRI indices between the groups studied. These data demonstrate that late-life depression, like DAT, in the absence of major vascular risk factors, is not associated with a significant increase in MRI high-intensity signals when compared to healthy, control subjects.",,"Miller, D. S.;Kumar, A.;Yousem, D. M.;Gottlieb, G. L.",1994,1994,,0,
2497,Brain lesions and cognitive function in late-life psychosis,"Twenty-four patients who developed their first psychotic episode after the age of 45 were studied with MRI and comprehensive neuropsychological testing and compared with 72 healthy elderly subjects. The patients demonstrated more clinical abnormalities on MRI, were more likely to have large white-matter lesions or metabolic illness, and did more poorly on many neuropsychological tests, particularly those testing frontal-lobe and memory abilities. We conclude that structural brain injury is commonly associated with the late onset of psychosis. Neuroimaging investigations are a valuable component in the evaluation of this patient group.","Aged;Brain/pathology;Brain Damage, Chronic/diagnosis/psychology;Dementia/*diagnosis/psychology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Neurocognitive Disorders/*diagnosis/psychology;*Neuropsychological Tests","Miller, B. L.;Lesser, I. M.;Boone, K. B.;Hill, E.;Mehringer, C. M.;Wong, K.",1991,Jan,,0,
2498,Brain white-matter lesions and psychosis,"In a prospective study of late-life onset psychosis, five of the first 27 patients studied had extensive white-matter lesions demonstrated by MRI and/or CT. None of 60 age-matched psychiatrically healthy controls demonstrated such lesions. All five patients had a mild dementia and a frontal behavioural syndrome. In addition, every patient performed poorly on neuro-psychological tests of frontal function. Dysfunction of the frontal cortex associated with white-matter lesions appears to contribute to the clinical picture of some cases of late-life psychosis.",adult;age;brain injury;clinical article;dementia;human;priority journal;psychological aspect;psychosis;white matter,"Miller, B. L.;Lesser, I. M.;Boone, K.;Goldberg, M.;Hill, E.;Miller, M. H.;Benson, D. F.;Mehringer, M.",1989,,,0,
2499,Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser,"The total volumes and relative quantities of grey and white matter have been measured in sixty-five normal male and sixty-five normal female cerebral hemispheres. Fixed hemisphere volume was found to fall linearly at 3.5% per decade for men from 641 ml at the age of 20 to 463 ml at the age of 100. For women the decrease was 1.9% per decade from 531 ml at 20 years to 462 ml at 100 years. After correction for the effects of fixation and for the secular increase in brain size, it was concluded that mean hemisphere volume remained roughly constant between the ages of 20 and 50 years (558 ml for men, 474 ml for women). After the age of 50 the mean volume in both sexes fell at about 2% per decade. The ratio of the volumes of grey to white matter was the same for the two sexes at all ages. Its mean value was 1.3 at the age of 20, falling to 1.1 at the age of 50, then rising steadily to over 1.5 at 100 years. It is impossible in practice to correct these measurements for the effects of fixation or secular change. Fourteen hemispheres from thirteen elderly female dements were also measured. The total volume was 18% lower than for an age-matched group of normals, but the ratio of grey to white matter was identical.",Adult;Aged;Aging;Alzheimer Disease/radionuclide imaging;Brain/ growth & development/radionuclide imaging;Female;Humans;Male;Middle Aged;Sex Factors,"Miller, A. K.;Alston, R. L.;Corsellis, J. A.",1980,Mar-Apr,,0,
2500,Vertebrobasilar dolichoectatic arteries. Complications and prognosis,"Symptomatic dolichoectasia of the vertebrobasilar system was found in 23 patients (16 males and 7 females, mean age: 62 years) during a 13-year period. Arterial hypertension was noted in 20 cases and associated aortic ectasia in 4. The malformation was identified in all patients on CT completed by angiography in 19, MRI in 7. Autopsy was performed in 5 cases. Fourteen subjects (group I) presented with a vascular event (ischemic in 13) affecting the brainstem and/or cerebellum. Nine other patients (group 2) had a chronic symptomatology resulting from compression of the cranial nerves, central nervous system and/or CSF pathway. Two patients died of stroke within the first month (rupture of the ectasia in one and occlusion in the other one). The 21 survivors were followed for a mean period of 45.3 months. Eight patients had a stroke, with a significantly higher incidence in group 1 than in group 2 (p < 0,05). Ten patients (5 in each group) developed progressive dementia possibly resulting from multiple cerebral infarction, hypertensive leucoencephalopathy, and/or hydrocephalus. Twelve patients died during the follow-up (4 of stroke, 6 of profound mental and motor deterioration, one from ruptured ectatic aorta, and the last one of unrecognized cause). The actuarial survival rate was 60% after 3 years of follow-up. Except for the incidence of stroke, inaugural manifestations (stroke vs nervous compression) did not seem to influence the long-term prognosis.",adult;aged;article;basilar artery;brain angiography;clinical article;computer assisted tomography;female;human;human tissue;hypertension;male;priority journal;cerebrovascular accident;vertebral artery,"Milandre, L.;Bonnefoi, B.;Pestre, P.;Pellissier, J. F.;Grisoli, F.;Khalil, R.",1991,,,0,
2501,Extensive cortico-subcortical lesions in Wilson's disease: Clinico-pathological study of two cases,"Wilson's disease (WD) with extensive cortico-subcortical lesions represents a rare neuropathological subgroup, the pathogenesis of which is not clearly determined. We report two new cases with identical lesions. In the families of each of the patient, there were mutations in the ATPase7B gene, especially in the family of proband 1, and in the first cousin of proband 2. These cases included massive destruction of the white matter in superior gyri, mostly frontal, extending to the deep cortex with neuronal loss and capillary proliferation. Astrocytes were of Alzheimer type 1 and 2; and type 1 were labeled by anti-metallothionein. Opalski cells were abundant and their macrophagic lineage was confirmed by immunostaining. Among the possible mechanisms proposed, the role of vascular factors and penicillamine treatment could be excluded. Cerebral copper content in white matter and putamen of case 1 was at the same level as in common WD but accumulation of unbound copper in the white matter was a distinctive feature, which suggested a pathological neurotoxic effect. © Springer-Verlag 2005.",copper;penicillamine;thiamine;zinc sulfate;adult;article;astrocyte;brain cortex lesion;case report;clinical feature;clinical protocol;computer assisted tomography;copper metabolism;death;disease exacerbation;female;gene mutation;human;human tissue;immunohistochemistry;male;molecular genetics;nuclear magnetic resonance imaging;pathogenesis;pedigree analysis;priority journal;pyramidal sign;white matter;Wilson disease,"Mikol, J.;Vital, C.;Wassef, M.;Chappuis, P.;Poupon, J.;Lecharpentier, M.;Woimant, F.",2005,,,0,
2502,Magnetic resonance spectroscopic study of Alzheimer's disease and frontotemporal dementia/Pick complex,"Disease-specific metabolic changes in Alzheimer's disease and frontotemporal dementia/Pick complex were examined by proton magnetic resonance spectroscopy at 3.0 T. Spectra were acquired from posterior and anterior cingulate cortices and the parieto-occipital and frontal white matter. This study included eight Alzheimer's disease patients, 10 frontotemporal dementia/Pick complex patients and 14 healthy volunteers. N-acetylaspartate/creatine+phosphocreatine ratio was reduced in the posterior cingulate cortex in the Alzheimer's disease and frontotemporal dementia/Pick complex patients. The Alzheimer's disease patients, however, showed a posterior dominant decrease, whereas the frontotemporal dementia/Pick complex patients showed a frontal predominant decrease. These different distributions of metabolic changes may represent the underlying pathological processes in each disease. Our standardized protocol of proton magnetic resonance spectroscopy measurement may be helpful in differentiating these dementia subtypes.",Aged;Alzheimer Disease/*diagnosis/metabolism/physiopathology;Aspartic Acid/analogs & derivatives/metabolism;Brain Mapping;Cerebral Cortex/metabolism/pathology/*physiopathology;Creatine/metabolism;Dementia/*diagnosis/metabolism/physiopathology;Down-Regulation/physiology;Energy Metabolism/physiology;Female;Frontal Lobe/metabolism/pathology/physiopathology;Gyrus Cinguli/metabolism/pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Parietal Lobe/metabolism/pathology/physiopathology;Pick Disease of the Brain/*diagnosis/metabolism/physiopathology,"Mihara, M.;Hattori, N.;Abe, K.;Sakoda, S.;Sawada, T.",2006,Mar 20,10.1097/01.wnr.0000203353.52622.05,0,
2503,Functional connectivity of ventral and dorsal visual streams in posterior cortical atrophy,"Background: Posterior cortical atrophy (PCA) induces progressive dysfunction of ventral and dorsal visual networks.∗Little is known, however, about corresponding changes in functional connectivity (FC).∗Objectives: To investigate FC changes in the visual networks, their relationship with cortical atrophy, and the association with Alzheimer's disease (AD) pathology.∗Methods: Ten PCA patients and 28 age-matched controls participated in the study.∗Using resting state fMRI, we measured FC in ventral and dorsal cortical visual networks, defined on the basis of a priori knowledge of long-range white matter connections.∗To assess the relationships with AD, we determined AD biomarkers in cerebrospinal fluid and FC in the default mode network (DMN), which is vulnerable to AD pathology.∗Voxel-based morphometry analysis assessed the pattern of grey matter (GM) atrophy.∗Results: PCA patients showed GM atrophy in bilateral occipital and inferior parietal regions.∗PCA patients had lower FC levels in a ventral network than controls, but higher FC in inferior components of the dorsal network. In particular, the increased connectivity correlated with greater GM atrophy in occipital regions.∗All PCA patients had positive cerebrospinal fluid biomarkers for AD; however, FC in global DMN did not differ from controls.∗Conclusions: FC in PCA reflects brain structure in a non-univocal way. Hyperconnectivity of dorsal networks may indicate aberrant communication in response to posterior brain atrophy or processes of neural resilience during the initial stage of brain dysfunction. The lack of difference from controls in global DMN FC highlights the atypical nature of PCA with respect to typical AD.",biological marker;adult;Alzheimer disease;article;brain cortex atrophy;cerebrospinal fluid;clinical article;connectome;controlled study;default mode network;disease association;female;functional connectivity;functional magnetic resonance imaging;functional neuroimaging;human;inferior parietal cortex;male;neuropathology;occipital cortex;priority journal;visual cortex;voxel based morphometry,"Migliaccio, R.;Gallea, C.;Kas, A.;Perlbarg, V.;Samri, D.;Trotta, L.;Michon, A.;Lacomblez, L.;Dubois, B.;Lehericy, S.;Bartolomeo, P.",2016,,,0,
2504,Brain networks in posterior cortical atrophy: A single case tractography study and literature review,"Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) Magnetic Resonance Imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways. © 2011 Elsevier Srl.",,"Migliaccio, R.;Agosta, F.;Toba, M. N.;Samri, D.;Corlier, F.;de Souza, L. C.;Chupin, M.;Sharman, M.;Gorno-Tempini, M. L.;Dubois, B.;Filippi, M.;Bartolomeo, P.",2012,November,,0,
2505,White matter atrophy in Alzheimer's disease variants,"BACKGROUND: In comparison with late-onset Alzheimer's disease (LOAD, onset, >65 years), early-age-of-onset Alzheimer's disease (EOAD, onset, <65 years) more often presents with language, visuospatial, and/or executive impairment, often occurring earlier than a progressive memory deficit. The logopenic variant of primary progressive aphasia (lv-PPA) and posterior cortical atrophy (PCA) have recently been described as possible atypical variants of EOAD. Lv-PPA is characterized by isolated language deficit, whereas PCA is characterized by predominant visuospatial deficits. Severe hemispheric gray matter (GM) atrophy associated with EOAD, lv-PPA, and PCA has been described, but regional patterns of white matter (WM) damage are still poorly understood. METHODS: Using structural magnetic resonance imaging and voxel-based morphometry, we investigated WM damage in patients with EOAD (n = 16), PCA (n = 13), lv-PPA (n = 10), and LOAD (n = 14) at presentation and 72 age-matched control subjects. RESULTS: In patients with EOAD, PCA, and lv-PPA, WM atrophy was centered on the lateral temporal and parietal regions, including the cingulum and posterior corpus callosum. Compared with control subjects, patients with lv-PPA showed more severe left parietal damage, and patients with PCA showed more severe occipital atrophy. Moreover, patients with EOAD had greater cingulum atrophy compared with those with LOAD. LOAD showed WM damage in the medial temporal regions and less extensive hemispheric involvement. CONCLUSION: Patterns of WM damage in EOAD, lv-PPA, and PCA are consistent with the clinical syndromes and GM atrophy patterns. WM injury in AD atypical variants may contribute to symptoms and disease pathogenesis.","Age of Onset;Aged;Alzheimer Disease/ pathology;Atrophy/pathology;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology","Migliaccio, R.;Agosta, F.;Possin, K. L.;Rabinovici, G. D.;Miller, B. L.;Gorno-Tempini, M. L.",2012,Oct,10.1016/j.jalz.2012.04.010,0,
2506,Positron emission tomography in the differentialdiagnosis and evaluation of Alzheimer's disease,"At present positron emission tomography (PET) is the only technology affording three-dimensional quantitative imaging of various aspects of brain physiology and disturbed cerebral function. Since function and metabolism are coupled, and since glucose is the main substrate of the cerebral metabolism, fluor deoxyglucose (FDG) is widely used to study glucose metabolism in organic brain disease. Due to loss of neurons and synapses Alzheimer's disease shows a typical metabolic pattern with hypometabolism in the frontal and temporoparietal association cortex and relative recess of primary conical areas and subcortical structures. In vascular dementia PET can clearly differentiate multiple focal metabolic reductions which are caused by disconnection of cortical areas due to subcortical infarction. As PET offers absolute metabolic data it can be used to monitor the effects of therapeutic trials in demented patients.",,"Mielke, R.;Kessler, J.;Herholz, K.;Heiss, W. D.",1996,1996,,0,
2507,Positron emission tomography for diagnosis of Alzheimer's disease and vascular dementia,"In mild or atypical cases of Alzheimer's disease (AD) the differential diagnosis to other dementing diseases, such as vascular dementia (VD), may pose a difficult problem. Beside computed tomography (CT) and magnetic resonance imaging (MRI), functional neuroimaging by positron emission tomography (PET) support the clinical diagnosis by visualizing cerebral function. PET of (18)F-2-fluoro-2-deoxy-D-glucose (FDG) for measurement of regional cerebral glucose metabolism (rCMRGl) has shown a typical metabolic pattern in patients with probable AD: hypometabolism in temporoparietal and frontal association areas, but relative recessing of primary cortical areas, basal ganglia and cerebellum. In VD a different pattern is seen. It consists of scattered areas with reduction of rCMRGl typically extending over cortical and subcortical structures. Severity of dementia is correlated with rCMRGl reduction in the temporoparietal association cortex, irrespective of the cause of dementia. Also the total volume of hypometabolic regions is related to severity of dementia but did not differ between AD and VD, even in patients with small lacunar infarction. This indicates that the total volume of functional tissue loss is more important, since it also includes the effects of incompletely infarcted tissue and morphologically intact but deafferented cortex. The characteristic metabolic pattern has a high diagnostic accuracy for the discrimination between probable AD, normals and VD, even in patients with mild cognitive impairment. Under clinical and therapeutic aspects the analysis of longitudinal changes of rCMRGl has shown that neuropsychological and metabolic changes are closely related in both",,"Mielke, R.;Heiss, W. D.",1998,1998,,0,
2508,Impaired Cognition and Brain Atrophy Decades After Hypertensive Pregnancy Disorders,"BACKGROUND: Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white-matter lesions 5 to 10 years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown. METHODS AND RESULTS: This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study. As part of the ancillary Genetics of Microangiopathic Brain Injury (GMBI) study, a neurocognitive battery was administered; 1075 also had a brain magnetic resonance imaging. A history of a hypertensive pregnancy disorder was obtained by a self-report using a validated questionnaire. Linear models fit with generalized estimating equations were used to assess the association between hypertensive pregnancy disorders and cognition, adjusting for age, race, education, body mass index, smoking, current hypertension, hypertension duration, and family history of hypertension. Regression models for the brain magnetic resonance imaging outcomes also were adjusted for total intracranial volume. Women with histories of hypertensive pregnancy disorders performed worse on all measures of processing speed (Digital Symbol Substitution Test [mean score, 41.2 versus 43.4; P=0.005], Trail Making Test Part A [mean seconds, 45.1 versus 42.2; P=0.035], and Stroop [mean score, 173.9 versus 181.0; P=0.002]) and had smaller brain volumes compared with women with histories of normotensive pregnancies (286 versus 297; P=0.023). CONCLUSIONS: Hypertensive pregnancy disorders are associated with worse performance on tests of processing speed and smaller brain volumes decades later. Population-based studies are needed to provide critical insight as to the contribution of hypertensive pregnancies to risk of cognitive decline and dementia.",,"Mielke, M. M.;Milic, N. M.;Weissgerber, T. L.;White, W. M.;Kantarci, K.;Mosley, T. H.;Windham, B. G.;Simpson, B. N.;Turner, S. T.;Garovic, V. D.",2016,Jan,10.1161/circoutcomes.115.002461,0,
2509,"Preliminary quantitative evaluation of 18F-FDDNP PET/CT in Alzheimer's disease, using different regions of reference","Introduction: Alzheimer's disease (AD) is the leading cause of dementia in the world. His current treatment is symptomatic. New therapies, aimed at slowing the neurodegenerative process, are actually under study. Early detection of AD as also the evaluation of new generation of neuroprotectors drugs is essential. For this reason, markers of amyloid plaques and neurofibrillary lesions have been developed including 18F-FDDNP. Methods: Two patients and two controls were included in this preliminary study. They were submitted to a PET/CT with 18F-FDDNP. Data acquisition was performed in a list mode during 90minutes. We used a cerebral atlas to create ROI, after co registration with a perfusion PET template, and we estimated the distribution volume ratio (DVR) using two different reference regions: the cerebellum and the white matter. We calculated a simplified index of quantification (SUVr) using a single 10minutes acquisition frame. Results: We found an increased DVR in temporal lobes (amygdala) (1.23-1.40 in patients vs 1.06-1.31 in controls, with cerebellum as reference region) and fronto-basal regions (1.48-1.30 in patients vs 1.16-1.23 in controls with the same reference region and 1.25-1.18 in patients vs 1.13-1.19 in controls with white matter as reference region). SUVr calculated between 50 and 60. minutes after injection was highly correlated to DVR values (correlation coefficient 0.93). The SUVr difference between patients and controls was more important with cerebellum rather than white matter as reference region (26% in amygdala). Conclusion: This is a very preliminary study due to the low number of subjects included. However, the results obtained suggest the feasibility of brain ROI segmentation and the DVR-SUVr calculation using an anatomical atlas. © 2013 Published by Elsevier Masson SAS.",fddnp f 18;radiopharmaceutical agent;unclassified drug;Alzheimer disease;article;case report;cerebellum;computer assisted emission tomography;controlled study;volume of distribution;human;temporal lobe;white matter,"Michaud, L.;Venel, Y.;Le Borgne, A.;Santiago-Ribeiro, M. J.;Guilloteau, D.;Tauber, C.;Baulieu, J. L.",2013,,,0,
2510,Dialysis and transplantation affect cerebral abnormalities of end-stage renal disease,"Localized short echo time proton magnetic resonance spectroscopy was performed to determine whether chronic and end-stage renal failure, hemodialysis, continuous ambulatory peritoneal dialysis, or renal transplantation result in alterations of cerebral water and metabolites in humans. Hemodialysis patients show an increased cerebral concentration of myo-inositol (+ 14%; P < .05). Increased metabolite ratios are found for myo-inositol/creatine (+14%; P <.01) and choline containing compounds choline/creatine (+10%; P < .01) and are more marked in gray than in white matter. N-acetylaspartate and total creatine concentrations are unaffected. Compared to hemodialysis, continuous ambulatory peritoneal dialysis patients show a larger increase in choline and less elevated myo-inositol. Acutely, hemodialysis significantly decreases the cerebrospinal fluid content of the examined brain regions, but metabolite changes are small compared to the persistent alterations in patients receiving hemodialysis or continuous ambulatory peritoneal dialysis. Undialyzed patients with chronic renal failure do not differ from patients on hemodialysis, but cerebral metabolite changes are completely reversed by transplantation. Cerebral metabolic effects of end-stage renal disease differ from Alzheimer's disease, which is associated with markedly reduced N-acetylaspartate, increased myo-inositol, and normal choline concentrations. The small but significant cerebral metabolic disorders associated with renal failure and dialysis may be a consequence of osmotic dysregulation.",aspartic acid;choline;diagnostic agent;drug derivative;inositol;n acetylaspartic acid;adult;article;body water;brain;brain disease;chronic kidney failure;continuous ambulatory peritoneal dialysis;female;human;kidney transplantation;male;metabolism;middle aged;nuclear magnetic resonance spectroscopy;renal replacement therapy,"Michaelis, T.;Videen, J. S.;Linsey, M. S.;Ross, B. D.",1996,,,0,
2511,Delayed neurotoxicity of intraventricular interleukin-2: A case report,"A case is reported of a 40 year old woman treated with intraventricular IL-2 for leptomeningeal disease who developed progressive cognitive dysfunction. This deterioration started 3 months post-treatment and worsened over the ensuing 4 years. MRI revealed white matter abnormalities that were not present on the pretreatment scan. Although free of disease, the patient has a subcortical dementia and is unable to work. The potential for progressive brain injury and subsequent disability related to intraventricular IL-2 therapy is discussed.",interleukin 2;adult;article;brain injury;brain toxicity;dementia;deterioration;female;human;human cell;human tissue;immunotherapy;intracerebroventricular drug administration;meninx disorder;work capacity,"Meyers, C. A.;Yung, W. K. A.",1993,,,0,
2512,Neurocognitive effects of therapeutic irradiation for base of skull tumors,"PURPOSE: To determine whether radiation therapy delivered to the paranasal sinuses causes any long-term impairment in neurocognitive function as a result of incidental brain irradiation. METHODS AND MATERIALS: Nineteen patients who received paranasal sinus irradiation at least 20 months and up to 20 years before assessment were given a battery of neuropsychologic tests of cognitive function. Radiation was delivered by a three-field (one anteroposterior and two lateral) technique. The median radiation dose was 60 Gy (range 50-68 Gy) in fractions of 1.8 to 2 Gy. The volume of irradiated brain was calculated from planning computed tomography slices or simulation films. The results of the neuropsychologic tests were compared to normative control values. RESULTS: Memory impairment was found in 80% of the patients, and one-third manifested difficulty with visual-motor speed, frontal lobe executive functions, and fine motor coordination. Two of the patients had frank brain necrosis with resultant dementia and blindness, and three had evidence of brain atrophy. Three of the fourteen patients without documented cerebral atrophy or necrosis were disabled from their normal activities. Three patients also developed pituitary dysfunction. Neurocognitive symptoms were related to the total dose of radiation delivered but not to the volume of brain irradiated, side of radiation boost, or chemotherapy treatment. The pattern of test findings was consistent with radiation injury to subcortical white matter. CONCLUSIONS: Radiation therapy for paranasal sinus cancer may cause delayed neurocognitive side effects. Currently, however, the development of severe adverse effects appears to be decreasing because of improvements in the techniques used to deliver radiation. Lowering the total dose and improving dose distributions should further decrease the incidence of delayed brain injury due to radiation.","Adult;Aged;Brain/anatomy & histology/*radiation effects;Cognition Disorders/*etiology;Ethmoid Sinus;Female;Humans;Magnetic Resonance Imaging;Male;Maxillary Sinus Neoplasms/radiotherapy;Middle Aged;Neuropsychological Tests;Paranasal Sinus Neoplasms/radiotherapy;Radiation Injuries/*etiology;Retrospective Studies;Skull Base Neoplasms/*radiotherapy;Tomography, X-Ray Computed","Meyers, C. A.;Geara, F.;Wong, P. F.;Morrison, W. H.",2000,Jan 1,,0,
2513,Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites,"We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter. Chronic alcohol consumption was associated with reduced white matter concentrations of phosphodiester (PDE) and phosphocreatine (PCr). Also in the white matter, acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) were associated with reduced concentrations of PDE and PCr, compared with both HIV- and clinically asymptomatic HIV+ subjects. Because no alcohol-by-HIV interactions were detected, the effects of HIV infection and alcohol abuse were cumulative. This is reflected in a successive decrease of white matter PDE and PCr concentrations in the order HIV- light/nondrinkers/HIV- alcoholics/HIV+ light/nondrinkers/HIV+ alcoholics. Subcortical gray matter PDE concentrations were lower in ARC/AIDS alcoholics than in HIV- light/nondrinking individuals. These findings suggest altered brain phospholipid metabolites and energy metabolites with alcohol abuse and HIV infection. They demonstrate that the adverse metabolic effects of HIV on the brain are augmented by chronic alcohol abuse.",AIDS Dementia Complex/ physiopathology;AIDS-Related Complex/physiopathology;Acquired Immunodeficiency Syndrome/physiopathology;Adenosine Triphosphate/metabolism;Adult;Alcoholism/complications/ physiopathology;Brain/pathology/ physiopathology;Brain Mapping;HIV Seropositivity/ physiopathology;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Organophosphates/metabolism;Phosphocreatine/metabolism;Phosphorus/ metabolism,"Meyerhoff, D. J.;MacKay, S.;Sappey-Marinier, D.;Deicken, R.;Calabrese, G.;Dillon, W. P.;Weiner, M. W.;Fein, G.",1995,Jun,,0,
2514,Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging,"We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolites, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate-choline ratio) and creatine-containing metabolites (N-acetylaspartate-creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline-N-acetylaspartate ratios with the N-acetylaspartate-creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.",Aged;Aging/metabolism;Alzheimer Disease/ diagnosis/metabolism;Aspartic Acid/analogs & derivatives/metabolism;Axons/metabolism;Brain/anatomy & histology/ metabolism;Cerebral Cortex/metabolism;Cerebral Ventricles/anatomy & histology;Choline/metabolism;Creatine/metabolism;Female;Humans;Magnetic Resonance Spectroscopy;Male;Middle Aged,"Meyerhoff, D. J.;MacKay, S.;Constans, J. M.;Norman, D.;Van Dyke, C.;Fein, G.;Weiner, M. W.",1994,Jul,10.1002/ana.410360110,0,
2515,CT changes associated with normal aging of the human brain,"CT was used to measure changes in cerebral gray and white matter tissue densities associated with normal aging, using a cross-sectional design, in order to provide normative data for comparisons with abnormal aging such as dementias of Alzheimer's and vascular types. Cerebral compartmental densities were measured using plain CT, and their perfusion values were recorded during stable xenon inhalation (CT-CBF), among 81 neurologically and cognitively normal volunteers of different ages. Results led to the conclusion that cortical gray matter tissue densities progressively decline (polio-araiosis) after age 60. Cortical polio-araiosis is coupled with regional hypoperfusion but not with cortical atrophy. It is speculated that the cortical hypodensity identified by CT imaging parallels declines in cortical synaptic density, as reported from autopsy studies using anti-synaptophysin staining of cerebral cortex obtained from normal people above and below age 60. The coupling of cortical hypoperfusion with polio-araiosis is believed to reflect age-related reductions of cortical metabolic demands as reported by PET. During normal aging leuko-araiosis correlates directly with cortical atrophy, suggesting that anterograde axonal degeneration resulting from cortical neuronal dearborization play a role in its causation.","Adult;Aged;Aged, 80 and over;Aging/ physiology;Brain/blood supply/growth & development/ radiography;Cerebral Cortex/growth & development/radiography;Cerebrovascular Circulation;Female;Humans;Male;Middle Aged;Reference Values;Synaptophysin/analysis;Tomography, X-Ray Computed","Meyer, J. S.;Takashima, S.;Terayama, Y.;Obara, K.;Muramatsu, K.;Weathers, S.",1994,May,,0,
2516,"Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia","Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT, densitometry, perfusions, and cognitive testing among neurologically and cognitively normative aging volunteers. A total of 224 normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59.5 +/- 15.8 years. Mean follow-up is 5.8 +/- 3.3 years. At follow-up, 22 developed mild cognitive impairment (41 CCSE >/= -3), 19 became demented-8 with Vascular type (VAD), 11 with Alzheimer's type (DAT)-and 183 remain cognitively unchanged. Cerebral atrophy, tissue densities, and perfusions were measured by Xe-CT. After age 60, cerebral atrophy, ventricular enlargement, and polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis, and leuko-araiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, and male gender. At age 71.5 +/- 11.9, mild cognitive impairment began accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with VAD. Excessive cortical perfusional decrease, gray and white matter hypodensities, and cerebral atrophy correlate with cognitive decline.","Adult;Aged;Aged, 80 and over;Aging/psychology;Alcohol Drinking/epidemiology;Brain/radiography;Cerebrovascular Circulation/physiology;Cerebrovascular Disorders/complications/*epidemiology/psychology;Cognition Disorders/*epidemiology/psychology;Dementia, Vascular/*epidemiology/psychology;Densitometry;Diabetes Complications;Education;Female;Heart Diseases/complications;Humans;Hypertension/complications;Male;Middle Aged;Psychiatric Status Rating Scales;Risk Factors;Sex Factors","Meyer, J. S.;Rauch, G.;Rauch, R. A.;Haque, A.",2000,Mar-Apr,,0,
2517,Stable xenon CT CBF measurements in prevalent cerebrovascular disorders (stroke),"Local cerebral blood flow (LCBF) and local tissue: blood partition coefficient (L lambda) values were measured for small volumes of gray or white matter by CT CBF. Single compartment analysis was used but fitted to infinity in normal volunteers aged between 20 to 100 years (N = 20). Hemispheric LCBF and L lambda values were compared to those of 61 age matched patients with transient ischemic attacks (TIAs, N = 10), reversible ischemic neurologic deficits (RINDS, N = 10), acute and chronic cerebral infarctions associated with emboli from atherosclerotic plaques or complete occlusion of internal carotid or middle cerebral arteries (n = 9) or of cardiac origin (N = 3), cerebral hemorrhage (N = 1), multi-infarct dementia (MID) (N = 11) and arteriovenous malformations (AVM) (N = 17). In normal aging, L lambda s were normal, but LCBF showed diffuse age-related declines. Symptomatic cerebrovascular disease was characterized by accentuation of age-related LCBF declines. TIAs with unilateral ICA occlusion showed bilateral reductions of LCBF more evident in ischemic hemispheres. TIAs due to fibrino-platelet emboli from ulcerated, non-occlusive ICA plaques were characterized by transient unilateral, localized LCBF reductions. All TIAs showed normal L lambda values. RINDS showed both LCBF and L lambda reductions. Larger embolic infarctions of ICA origin, whether acute or chronic, showed zones of zero flow with surrounding reductions of LCBF and L lambda values. Recent cerebral embolism of cardiac origin likewise exhibited zones of zero flow surrounded by reduced LCBF and L lambda values; but in chronic stages LCBF and L lambda values adjacent to zero flow zones were normal. MID was characterized by patchy reductions of LCBF and L lambda values throughout both hemispheres. Brain tissues surrounding AVM showed normal L lambda values but LCBF values were reduced due to steal.","Adult;Aged;Cerebral Hemorrhage/physiopathology/radionuclide imaging;Cerebral Infarction/physiopathology/radionuclide imaging;*Cerebrovascular Circulation;Cerebrovascular Disorders/physiopathology/*radionuclide imaging;Dementia/physiopathology/radionuclide imaging;Humans;Intracranial Arteriosclerosis/physiopathology/radionuclide imaging;Intracranial Arteriovenous Malformations/physiopathology/radionuclide imaging;Intracranial Embolism and Thrombosis/physiopathology/radionuclide imaging;Ischemic Attack, Transient/physiopathology/radionuclide imaging;Male;Middle Aged;*Tomography, Emission-Computed;*Xenon Radioisotopes","Meyer, J. S.;Okayasu, H.;Tachibana, H.;Okabe, T.",1984,Jan-Feb,,0,
2518,"Problems encountered with longitudinal neurological, psychometric and cerebral CT imaging among stroke data bank patients with dementia","41 patients (30 men, 11 women, mean age 65.3 +/- 9.7 years) with probable ischemic vascular dementia diagnosed according to stated clinical criteria at least 3 months after hospital discharge and among a few nonhospitalized subjects with thorough clinical, neurovascular and neuroimaging workup have been followed for the past 7 years with serial measures of neurological and cognitive status and cerebral blood flow using stable xenon-enhanced CT. Cognitive impairments correlated with cerebral ischemia rather than CT measurements of infarcted brain volume. A minimum of one follow-up was required and follow-up intervals ranged from 4 months to 6.6 years (mean 3.4 +/- 1.6 years). 9 patients (22.0%) were lost to follow-up, 4.9% died, 9.8% became incapacitated by additional strokes, 2.4% by cancer and 4.9% moved away. Cross-sequential designs adjust for problems of attrition. Mortality rates of 1.4%/year during 1986-1993 are significantly lower than 2.0%/year between 1983 and 1986. Declines in mortality are attributed to control of risk factors and antiplatelet treatment of atherosclerotic cerebral vascular disease and anticoagulant treatment of patients with cardiogenic embolism.","Aged;Brain/blood supply;Databases, Factual/ statistics & numerical data;Dementia, Vascular/diagnosis/ epidemiology/mortality;Female;Follow-Up Studies;Humans;Male;Middle Aged;Neurologic Examination/ statistics & numerical data;Neuropsychological Tests/ statistics & numerical data;Psychometrics;Regional Blood Flow/physiology;Survival Rate;Tomography, X-Ray Computed/ statistics & numerical data","Meyer, J. S.;Obara, K.;Takashima, S.;Muramatsu, K.;Mortel, K. F.",1994,,,0,
2519,Prospective CT confirms differences between vascular and Alzheimer's dementia,"BACKGROUND AND PURPOSE: Cognitive test performances were correlated prospectively with changes in cerebral CT measurements of atrophy, infarct volume, ventricular enlargement, local tissue density, and local perfusion to contrast annual rates of changes among patients with ischemic vascular dementia (IVD) or dementia of the Alzheimer type (DAT). METHODS: The cerebral atrophic index (ATI; ratio of cerebrospinal fluid or infarcted brain to intracranial volume), infarct volume ratio, ventricular volume ratio (VVR; ventricular volume/intracranial volume), cortical and subcortical gray and white matter local perfusion (local cerebral blood flow [LCBF]), and local Hounsfield unit (HU) density were measured concurrently and compared longitudinally with Cognitive Capacity Screening Examinations (CCSE) scores among 24 treated IVD (age, 68.2 +/- 9.7 years; follow-up, 42 +/- 27 months) and 24 DAT patients (age, 74.2 +/- 6.2 years; follow-up, 30 +/- 19 months). RESULTS: IVD annual changes were as follows: CCSE, +1.2 +/- 5.9; ATI, +2.1%/y; VVR, +3.2%/y; and LCBF in the subcortical basal ganglia, -0.74 mL.100 g-1.min-1.y-1 (-1.8%/y). DAT annual changes were as follows: CCSE, -1.8/y; ATI, +8.1%/y; VVR, +9.6%/y; cortical LCBF, -2.0 mL.100 g-1.min-1.y-1 (-5.2%/y); LCBF in the basal ganglia, -3.0 mL.100 g-1.min-1.y-1 (-6.7%/y); white matter LCBF, -0.75 mL.100 g-1.min-1.y-1 (-4.1%/y); and all cortical tissue densities, -0.83 HU/y (-2.1%/y). In IVD, multiple regression analyses correlated cognitive changes directly with (1) recurrent silent infarctions and (2) bidirectional changes of perfusions within frontal white matter, thalamus, and internal capsules. In DAT, cognitive declines correlated with cerebral atrophy and cortical hypoperfusion related to frontotemporal and parietal cortical polioaraiosis (decreased gray matter tissue densities). CONCLUSIONS: In IVD, recurrent strokes were not observed clinically during risk factor control, and antiplatelet therapy and cognitive impairments improved or stabilized. In DAT, cognitive performance relentlessly declined. Ischemic pathogenesis for vascular dementia is supported by the following: (1) cognitive declines correlate directly with recurrent ""silent"" strokes, and (2) bidirectional cognitive changes correlate directly with frontal white matter, thalamic, and internal capsular perfusional changes.","Aged;Aged, 80 and over;Alzheimer Disease/physiopathology/*radiography;Brain/blood supply/*radiography;Cognition;Dementia, Vascular/physiopathology/*radiography;Female;Humans;Male;Microcirculation;Middle Aged;Prospective Studies;*Tomography, X-Ray Computed","Meyer, J. S.;Muramatsu, K.;Mortel, K. F.;Obara, K.;Shirai, T.",1995,May,,0,
2520,Vasodilator responses to acetazolamide tested in subtypes of vascular dementia,"OBJECTIVES: Thirty seven vascular dementia (VAD) patients were categorized into eight subtypes based on clinical, radiological, and pathogenetic features. Cerebral vasodilator responses to acetazolamide were then compared with age-matched normal controls and stroke patients without dementia. METHODS: VAD results were compared with 42 normals and 19 cognitively intact stroke patients. Regional cerebral vasodilator responses were quantitated utilizing xenon contrasted computed tomography measures of local cerebral blood flow (LCBF) before and after oral administration of acetazolamide. LCBF changes (DeltaLCBF) before and after acetazolamide were calculated within cortical and subcortical, gray and white matter. Clinical VAD subtypes were: type 1, multi-infarct dementia (MID); type 2, strategically placed infarcts; type 3, subcortical lacunar infarcts; type 4, Binswanger's subcortical arteriosclerotic leukoencephalopathy; type 5, subcortical infarctions due to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), inflammatory angitis, or antiphospholipid antibodies; type 6, admixtures of above types; type 7, cerebral hemorrhagic lesions; and type 8, VAD combined with Alzheimer's disease (DAT). The group with subcortical VAD comprised types 3-5. The group with cortical VAD comprised the remainder (types 1, 2, and 6-8). Cerebral vasodilator responses were also compared between these two main groups. RESULTS: Cerebral vasodilator responses identified differences between the two main groups of VAD patients, those with cortical and those with subcortical dementia. Leukoaraiosis was measurably greater in subcortical VAD compared with cortical VAD. Among subcortical VAD patients, cortical LCBF increases after administration of acetazolamide were greater compared with cortical VAD and with normal controls. CONCLUSIONS: Cognitive impairments in subcortical VAD are attributable to cortical disconnection syndromes. This concept is supported by reduced perfusion in deactivated cortex. In patients with subcortical VAD, deactivated cortical LCBF becomes promptly activated by acetazolamide resulting in marked cortical LCBF increases. Leukoaraiosis is greater among VAD patients and leukoaraiosis contributes to cortical disconnections, confirmed by excessive cortical vasodilator responses to acetazolamide.",,"Meyer, J. S.;Konno, S.;Margishvili, G. M.;Terayama, Y.",1998,Sep-Oct,,0,
2521,"MRI confirms mild cognitive impairments prodromal for Alzheimer's, vascular and Parkinson-Lewy body dementias","OBJECTIVES: MRI assessments were correlated with serial Combined Mini-Mental Cognitive Capacity Screening Examinations (CMC). Vascular-MCI (VMCI), Neurodegenerative MCI (NMCI) and Parkinson-Lewy body MCI (PLB-MCI) were compared during conversions to dementia. Mild cognitive impairments (MCI) are identifiable prodromes for all dementia subtypes. MRI abnormalities are characterized among MCI subjects prodromal for dementia of Alzheimer's disease (DAT), vascular dementia (VaD) and Parkinson-Lewy body dementia (PLBD). METHODS: Aging volunteers (n=166) were recruited from ongoing longitudinal studies of aging, stroke, cerebrovascular disease and dementia. Cognitively normal (CN, n=52), MCIs of neurodegenerative (N-MCI, n=30), vascular (V-MCI, n=35) and Parkinson-Lewy Body (PLB-MCI, n=8) subtypes, plus converted DAT (n=19), VaD (n=17) and PLBD (n=5) were all diagnosed according to established protocol recommendations. Cerebral MRI abnormalities were likewise intercorrelated utilizing quantitative volumetric measurements. RESULTS: V-MCI and converted VaD showed extensive leukoaraiosis with more lacunar infarcts than subjects with N-MCI or PLB-MCI. N-MCI, prodromal for DAT, showed medial temporal atrophy, greater enlargement of temporal horns, and fewer vascular lesions. PLB-MCI, prodromal for PLBD, displayed third ventricular enlargement greater than N-MCI and V-MCI, with similar but less severe atrophy of medial temporal lobe than N-MCI and fewer vascular lesions than V-MCI. Cognitive Impairments due to PLB with vascular features (V-PLB-CI) showed more lacunar and microvascular lesions involving both white matter and basal ganglia with greater frontal horn enlargement. CONCLUSIONS: This study confirms different MCI subtypes prior to conversion to different dementias listed, recognizable by specific MRI abnormalities.","Aged;Alzheimer Disease/diagnosis/physiopathology/psychology;Atrophy/etiology/pathology/physiopathology;Brain/blood supply/*pathology/physiopathology;Cerebral Arteries/pathology/physiopathology;Cognition Disorders/*diagnosis/physiopathology/*psychology;Dementia/*diagnosis/physiopathology/*psychology;Dementia, Vascular/diagnosis/physiopathology/psychology;Diagnosis, Differential;Disease Progression;Female;Humans;Lewy Body Disease/diagnosis/physiopathology/psychology;Magnetic Resonance Imaging/*methods/standards;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Prognosis","Meyer, J. S.;Huang, J.;Chowdhury, M. H.",2007,Jun 15,10.1016/j.jns.2007.01.016,0,
2522,MRI abnormalities associated with mild cognitive impairments of vascular (VMCI) versus neurodegenerative (NMCI) types prodromal for vascular and Alzheimer's dementias,"BACKGROUND AND OBJECTIVES: Mild Cognitive Impairments (MCIs) are identifiable clinical entities, in neurodegenerative forms, as prodromal for Alzheimer's type (DAT) or in vascular forms, as prodromal for vascular dementia (VaD). The present longitudinal study compares and contrasts MRI abnormalities among MCI subjects as they progress to DAT versus VaD. Subjects converting to DAT and VaD confirmed ultimate diagnosis during MCI staging. In ""mixed cases"" the predominant MRI pathology was judged the primary cause. SUBJECTS AND METHODS: Subjects (n = 153) were selected from elderly outpatient volunteers who have been enrolled for 25 years in planned longitudinal studies of aging, stroke and dementia. Cognitively normal (CN, n = 52), MCI of neurodegenerative (N-MCI, n = 30) and vascular (V-MCI), n = 35) subtypes, plus converted DAT (n = 19) and VaD (n = 17) were diagnosed according to established protocols. Combined Mini-Mental-Cognitive Capacity Screening Examinations (CMC) screened, identified and confirmed MCIs or dementias. Cerebral MRI abnormalities were analyzed utilizing volumetric measurements and visual rating scales. RESULTS: Compared with persistently cognitively normal subjects, MCI subjects and converted dementias were significantly older without significant gender differences, but cognitively impaired subjects were older than the CN group since age is a risk factor for cognitive decline. Histories of hypertension, heart disease, diabetes mellitus, TIAs and strokes were more frequent among subjects with VMCI and VaD, confirming that all vascular risk factors contribute to vascular cognitive decline, but since vascular risk factors were treated, not all progressed to VAD. Family history of neurodegenerative disease, particularly DAT, were more prevalent among NMCI and converted DAT subjects. VMCI showed more extensive leucoaraiosis and lacunar infarcts than subjects with NMCI. NMCI, prodromal for dementia of Alzheimer's type (DAT), showed more medial temporal lobe atrophy with enlarged temporal horns, and fewer vascular lesions.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Cognition Disorders/*pathology;Dementia, Vascular/*pathology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/pathology;Neuropsychological Tests;Severity of Illness Index","Meyer, J. S.;Huang, J.;Chowdhury, M.",2005,Dec,,0,
2523,Improved Executive Function and Callosal White Matter Microstructure after Rhythm Exercise in Huntington's Disease,"BACKGROUND: Huntington's disease (HD) is an autosominal dominant neurodegenerative condition that leads to progressive loss of motor and cognitive functions. Early symptoms in HD include subtle executive dysfunction related to white and grey matter loss in cortico-striatal-thalamic loops. There is no cure for HD and hence a significant need for early intervention with the potential to delay the clinical onset of the disease. OBJECTIVE: The objective of the present pilot study was to devise a novel behavioural intervention involving drumming and rhythm exercises that targets early dysexecutive problems, such as difficulties in sequence and reversal learning, response speed, timing, and dual tasking. METHOD: One preclinical person and nine people with early to advanced stages of HD were recruited of whom five completed the two months intervention. The effects of rhythm exercise on executive function, basal ganglia volume, and white matter microstructure in the anterior corpus callosum, the anterior thalamic radiation, and the cortico-spinal tract were assessed post- relative to pre-training. RESULTS: After two months training, improvements in executive function and changes in white matter microstructure, notably in the genu of the corpus callosum that connects prefrontal cortices of both hemispheres, were observed. No changes in basal ganglia volume were present. CONCLUSION: This pilot study provides novel preliminary evidence that carefully targeted behavioural stimulation in HD can result in cognitive enhancement and improvements in callosal white matter microstructure.","Adult;Corpus Callosum/ pathology;Executive Function;Exercise Therapy/ methods;Female;Humans;Huntington Disease/diagnosis/ pathology/ physiopathology;Male;Middle Aged;Physical Conditioning, Human/methods;Pilot Projects;Treatment Outcome;White Matter/ pathology","Metzler-Baddeley, C.;Cantera, J.;Coulthard, E.;Rosser, A.;Jones, D. K.;Baddeley, R. J.",2014,,10.3233/jhd-140113,0,
2524,Local cerebral metabolic rates of glucose in movement and language disorders from positron tomography,"Positron computed tomography with [18F]fluorodeoxyglucose to measure glucose metabolism has shown changes in the brain distant to a focal area of infarction, demonstrating that what appears as a focal abnormality represents a more widespread functional process. Several approaches are presented to better understand quantitative metabolic data and focus on caudate and basal ganglia function. Area-to-area correlations in Parkinson's and Huntington's diseases showed decreases in the number of cortical relationships compared with control subjects, suggesting that the basal ganglia are involved with the ability of cortical regions to function together. In aphasia, caudate metabolism correlated with several language measures that suggested a role in some undefined basic process, seemingly related to Broca's area function. The studies presented suggest that the caudate may involve integrating the processing of language and cognition with the execution of the resulting response. Motor and cognitive function seem related to similar and overlapping brain systems. The disruption of such systems may result in loss of both cognitive and motor aspects of a function.",fluorodeoxyglucose f 18;radioisotope;Alzheimer disease;aphasia;brain infarction;central nervous system;clinical article;diagnosis;glucose brain level;glucose metabolism;human;Huntington chorea;language disability;motor dysfunction;nervous system;Parkinson disease;positron emission tomography,"Metter, J. E.;Riege, W. H.;Hanson, W. R.",1984,,,0,
2525,The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia,"Wernicke's aphasia is characterized by severe word and sentence comprehension impairments. The location of the underlying lesion site, known as Wernicke's area, remains controversial. Questions related to this controversy were addressed in 72 patients with primary progressive aphasia who collectively displayed a wide spectrum of cortical atrophy sites and language impairment patterns. Clinico-anatomical correlations were explored at the individual and group levels. These analyses showed that neuronal loss in temporoparietal areas, traditionally included within Wernicke's area, leave single word comprehension intact and cause inconsistent impairments of sentence comprehension. The most severe sentence comprehension impairments were associated with a heterogeneous set of cortical atrophy sites variably encompassing temporoparietal components of Wernicke's area, Broca's area, and dorsal premotor cortex. Severe comprehension impairments for single words, on the other hand, were invariably associated with peak atrophy sites in the left temporal pole and adjacent anterior temporal cortex, a pattern of atrophy that left sentence comprehension intact. These results show that the neural substrates of word and sentence comprehension are dissociable and that a circumscribed cortical area equally critical for word and sentence comprehension is unlikely to exist anywhere in the cerebral cortex. Reports of combined word and sentence comprehension impairments in Wernicke's aphasia come almost exclusively from patients with cerebrovascular accidents where brain damage extends into subcortical white matter. The syndrome of Wernicke's aphasia is thus likely to reflect damage not only to the cerebral cortex but also to underlying axonal pathways, leading to strategic cortico-cortical disconnections within the language network. The results of this investigation further reinforce the conclusion that the left anterior temporal lobe, a region ignored by classic aphasiology, needs to be inserted into the language network with a critical role in the multisynaptic hierarchy underlying word comprehension and object naming.",adult;aged;article;Boston naming test;brain atrophy;brain cortex;brain mapping;brain nerve cell;cerebrovascular accident;comprehension;cortical sensory aphasia;diagonal band of Broca;disease severity;female;human;language;language disability;language test;left hemisphere;major clinical study;male;middle aged;nerve cell necrosis;neuroanatomy;Northwestern Assessment of Verbs and Sentences;nuclear magnetic resonance imaging;parietal lobe;Peabody picture vocabulary test;premotor cortex;primary progressive aphasia;priority journal;Pyramids and Palm Trees Test;temporal cortex;temporal lobe;Wernicke area;Western aphasia battery;white matter injury,"Mesulam, M. M.;Thompson, C. K.;Weintraub, S.;Rogalski, E. J.",2015,,,0,
2526,Postmortem MRI as a useful tool for investigation of cerebral microbleeds,,"Brain/*blood supply/*pathology;Cerebral Hemorrhage/*pathology;Dementia, Multi-Infarct/*pathology;Hemosiderin/analysis;Humans;Macrophages/pathology;*Magnetic Resonance Imaging/methods;Postmortem Changes;Reproducibility of Results","Messori, A.;Salvolini, U.",2003,Feb,,0,
2527,"The relationships between atherosclerosis, heart disease, type 2 diabetes and dementia","Type 2 diabetes in the elderly is associated with increased incidence of vascular disease, particularly, atherosclerosis of large blood vessels. Together with other risk factors such as dyslipidemia, atherosclerosis increases the risk for coronary heart disease and stroke. Most studies that have examined the impact of type 2 diabetes and other heart disease risk factors on cognitive functions do not provide evidence that heart disease risk factors (with the possible exception of triglycerides) further increase the likelihood of observing cognitive deficits in diabetic patients. However, none of these studies used imaging techniques to evaluate atherosclerosis or evidence of cerebrovascular disease, such as infarctions. The few studies that have included brain imaging suggest that evidence of cerebrovascular disease further increases the risk for dementia in diabetic patients. The results of longitudinal studies suggest that diabetes is an independent risk factor for cognitive decline and dementia. The pattern of neuropsychological performance observed in type 2 diabetic patients appears to be the result of multiple interacting processes developing over time. In addition to the detrimental effects of protracted impaired glucose regulation on the central nervous system, type 2 diabetes pathology also encompasses the detrimental effects of associated complications such as cerebrovascular disease, which is likely the main cause of the observed processing speed/reaction time decrements.",,"Messier, C.;Awad, N.;Gagnon, M.",2004,July,,0,
2528,Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging,"Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia.",Aging;Cognition;Diffusion-weighted imaging;Mri;Microstructure;Neurites,"Merluzzi, A. P.;Dean, D. C., 3rd;Adluru, N.;Suryawanshi, G. S.;Okonkwo, O. C.;Oh, J. M.;Hermann, B. P.;Sager, M. A.;Asthana, S.;Zhang, H.;Johnson, S. C.;Alexander, A. L.;Bendlin, B. B.",2016,Jul,10.1016/j.neurobiolaging.2016.03.026,0,
2529,"[Retrospective analysis of routine-MRI and correlation with aetiology of dementia, severity and neuropsychology in a memory-clinic population] Retrospektive Analyse der MRT-Routinebefunde und Korrelation mit Demenzatiologie, Schweregrad und neuropsychologischen Befunden von Patienten aus einer universitaren Gedachtnisambulanz","BACKGROUND: The contribution of potential treatable dementia aetiologies diagnosed using cerebral imaging varied considerably in previous studies and was not evaluated in a recent larger German sample of patients from a memory clinic. MATERIAL AND METHODS: MRI images of 502 patients were retrospectively reassessed. Beside the proportion of potentially treatable dementia aetiology, the extent of whole brain atrophy (semiquantitative) and vascular white matter lesions were assessed. RESULTS: Mean age of the patients was 63.7 +/- 13.1 years; 49 % were female, mean MMST was 24.2 +/- 5.5. In 74 % there was an agreement between the clinical dementia syndrome and MRI. 9 % (45 patients) had clearly discrepant imaging results, according to MRI criteria (21 x ischaemia, 20 x normal pressure hydrocephalus (NPH), 4 x intracerebral haemorrhage). These patients could not not be differentiated using age and MMST alone as clinical criteria. There was a significant correlation between global brain atrophy and MMST (r = -0.32; p < 0.001) and white matter lesion score (r = 0.28; p < 0.001). CONCLUSION: In 9 % there was a clear discrepancy between MRI results and the clinical syndrome diagnosis in memory-clinic patients. As known from earlier studies and current German 3 rd generation guidelines, it is reasonable to perform MRI imaging in dementia to improve the aetiological and differential diagnoses and to detect a different aetiology that can be missed using the clinical dementia criteria alone.","0 (Apolipoproteins E);Aged;Alzheimer Disease/pathology;Apolipoproteins E/genetics;Atrophy;Brain/pathology;Cerebral Infarction/pathology/psychology;Dementia/cerebrospinal fluid/ diagnosis/pathology/ psychology;Depression/complications/psychology;Diagnosis, Differential;Female;Genotype;Humans;Hydrocephalus/complications/diagnosis;Intracranial Hemorrhages/complications/diagnosis;Magnetic Resonance Imaging;Male;Memory Disorders/cerebrospinal fluid/ diagnosis/ psychology;Middle Aged;Neuropsychological Tests;Retrospective Studies;Trail Making Test","Merkle, S.;Kreil, S.;Suttner, G.;Doelken, M.;Dorfler, A.;Richter-Schmidinger, T.;Kornhuber, J.;Weih, M.",2011,Nov,,0,
2530,"Retrospective analysis of routine-MRI and correlation with aetiology of dementia, severity and neuropsychology in a memory-clinic population","BACKGROUND: The contribution of potential treatable dementia aetiologies diagnosed using cerebral imaging varied considerably in previous studies and was not evaluated in a recent larger German sample of patients from a memory clinic. MATERIAL AND METHODS: MRI images of 502 patients were retrospectively reassessed. Beside the proportion of potentially treatable dementia aetiology, the extent of whole brain atrophy (semiquantitative) and vascular white matter lesions were assessed. RESULTS: Mean age of the patients was 63.7 +/- 13.1 years; 49 % were female, mean MMST was 24.2 +/- 5.5. In 74 % there was an agreement between the clinical dementia syndrome and MRI. 9 % (45 patients) had clearly discrepant imaging results, according to MRI criteria (21 x ischaemia, 20 x normal pressure hydrocephalus (NPH), 4 x intracerebral haemorrhage). These patients could not not be differentiated using age and MMST alone as clinical criteria. There was a significant correlation between global brain atrophy and MMST (r = -0.32; p < 0.001) and white matter lesion score (r = 0.28; p < 0.001). CONCLUSION: In 9 % there was a clear discrepancy between MRI results and the clinical syndrome diagnosis in memory-clinic patients. As known from earlier studies and current German 3 rd generation guidelines, it is reasonable to perform MRI imaging in dementia to improve the aetiological and differential diagnoses and to detect a different aetiology that can be missed using the clinical dementia criteria alone.","Aged;Alzheimer Disease/pathology;Apolipoproteins E/genetics;Atrophy;Brain/pathology;Cerebral Infarction/pathology/psychology;Dementia/cerebrospinal fluid/ diagnosis/pathology/ psychology;Depression/complications/psychology;Diagnosis, Differential;Female;Genotype;Humans;Hydrocephalus/complications/diagnosis;Intracranial Hemorrhages/complications/diagnosis;Magnetic Resonance Imaging;Male;Memory Disorders/cerebrospinal fluid/ diagnosis/ psychology;Middle Aged;Neuropsychological Tests;Retrospective Studies;Trail Making Test","Merkle, S.;Kreil, S.;Suttner, G.;Doelken, M.;Dorfler, A.;Richter-Schmidinger, T.;Kornhuber, J.;Weih, M.",2011,Nov,10.1055/s-0031-1281641,0,
2531,White Matter Hyperintensities in Older Adults and Motoric Cognitive Risk Syndrome,"INTRODUCTION: Motoric cognitive risk (MCR) syndrome is a recently described pre-dementia syndrome characterized by slow gait and cognitive complaints that has been implicated as a predictor of cognitive decline and dementia in older adults. Previous work suggests that cerebrovascular disease is associated with MCR. White matter hyperintensities (WMH) are postulated to be a product of cerebrovascular disease, and have been associated with impaired mobility and impaired cognition. This study aimed to determine if MCR is associated with regional WMH. METHODS: Two cross-cultural cohorts of non-demented older adults were examined: 174 from a French memory clinic (62.1% male, mean age 70.7 +/- 4.3 years) and 184 from an Indian community-dwelling cohort (55.4% male, mean age 66.2 +/- 5.2 years). Participants were evaluated for slow gait, cognitive complaints, and regional WMH via MRI (fluid attenuated inversion recovery) FLAIR sequence. RESULTS: Overall, 20.7% of participants met criteria for MCR, and 72.9% of participants had WMH on FLAIR. WMH in the frontal, parieto-occipital, temporal, basal ganglia, cerebellum, or brainstem were not associated with MCR in either of the two cohorts. CONCLUSION: WMH was not significantly associated with MCR in this studied sample of participants, suggesting that other cerebrovascular pathophysiological mechanisms, or combination of mechanisms, might underlie MCR.","Cerebrovascular disease;Cognition;Gait;Motoric cognitive risk;Vascular injury;White matter hyperintensities;commercial, or other conflicts of interest.","Mergeche, J. L.;Verghese, J.;Allali, G.;Wang, C.;Beauchet, O.;Kumar, V. G. P.;Mathuranath, P. S.;Yuan, J.;Blumen, H. M.",2016,,,0,
2532,Imaging findings associated with cognitive performance in primary lateral sclerosis and amyotrophic lateral sclerosis,"INTRODUCTION: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. METHODS: The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. RESULTS: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. CONCLUSION: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.",,"Meoded, A.;Kwan, J. Y.;Peters, T. L.;Huey, E. D.;Danielian, L. E.;Wiggs, E.;Morrissette, A.;Wu, T.;Russell, J. W.;Bayat, E.;Grafman, J.;Floeter, M. K.",2013,,10.1159/000353456,0,
2533,Bi-exponential 3D-T1rho mapping of whole brain at 3 T,"Detection of multiple relaxation pools using MRI is useful in a number of neuro-pathologies including multiple sclerosis (MS), Alzheimer's, and stroke. In this study we evaluate the feasibility of using T1rho imaging for the detection of bi-exponential decays in the human brain. A prospective T1rho imaging study was performed on model relaxation phantoms (eggs) and 7 healthy volunteers. The data was fitted using a single pool and a 2-pool model to estimate mono- and bi-exponential T1rho maps, respectively. Bi-exponential decays were identified in the gray matter (GM) and white matter (WM) of the brain with 40.5% of GM, and 65.1% of WM pixels showing two T1rho relaxation pools (significance level P < 0.05). Detection of T1rho based bi-exponential decays in the brain provides complimentary information to T2 based contrast regarding the in vivo micro-environment in the brain.",,"Menon, R. G.;Sharafi, A.;Windschuh, J.;Regatte, R. R.",2018,Jan 19,,0,
2534,Artery of Percheron occlusion: Role of diffusion-weighted imaging in the early diagnosis,"Bilateral thalamic infarcts have a low frequency among different subtypes of strokes. Since it does not involve a particular vascular territory, it therefore usually involves the occlusion of the artery of Percheron (AOP). Here we report a 79-year-old right-handed Parkinsonian female patient, who was found unresponsive in bed. On examination, the patient was drowsy with a Glasgow Coma Score (GCS) of 10/15 (E2M5V3). She had absent doll's eye response with anisocoric pupils and intermittent vertical gaze palsy. Although the 1/17/2017 11:11:37 AMpatient had no apparent motor deficits, she was in a state of persistent somnolence with memory impairment and lack of initiative. Diffusion-weighted magnetic resonance imaging (MRI) of the brain showed focal areas of restricted diffusion in the medial part of the thalami bilaterally and the rostral part of mid-brain (right > left) (bilateral paramedian thalamic with mid-brain pattern), suggestive of a hyper-acute infarct in the territory of AOP. The patient was anticoagulated with 40 mg subcutaneous low molecular weight heparin and was started on double anti-platelets along with supportive measures. The level of consciousness is improved at a slow rate to a GCS of 12/15 (E4M5V3). The patient had marked abulia with periods of drowsiness interspersed with periods of restlessness and uttering of abnormal sounds, but she was able to execute simple commands. In conclusion, occlusion of the AOP is a rare cause of coma in elderly patients. Diffusion-weighted MRI is the imaging modality of choice for early diagnosis. Early diagnosis of AOP occlusion may lead to favorable outcomes.",low molecular weight heparin;aged;anticoagulant therapy;artery of Percheron occlusion;article;Babinski reflex;case report;computer assisted tomography;diffusion weighted imaging;drowsiness;early diagnosis;female;follow up;gaze paralysis;Glasgow coma scale;human;memory disorder;Mini Mental State Examination;nuclear magnetic resonance imaging;occlusive cerebrovascular disease;parkinsonism;physical examination;posterior cerebral artery;somnolence,"Menon, M. K.;Jacob, S. M.;Jalal, M. J. A.",2016,,10.4103/2347-8659.169916,0,
2535,Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis,"Diagnosis, stratification and monitoring of disease progression in amyotrophic lateral sclerosis currently rely on clinical history and examination. The phenotypic heterogeneity of amyotrophic lateral sclerosis, including extramotor cognitive impairments is now well recognized. Candidate biomarkers have shown variable sensitivity and specificity, and studies have been mainly undertaken only cross-sectionally. Sixty patients with sporadic amyotrophic lateral sclerosis (without a family history of amyotrophic lateral sclerosis or dementia) underwent baseline multimodal magnetic resonance imaging at 3 T. Grey matter pathology was identified through analysis of T1-weighted images using voxel-based morphometry. White matter pathology was assessed using tract-based spatial statistics analysis of indices derived from diffusion tensor imaging. Cross-sectional analyses included group comparison with a group of healthy controls (n = 36) and correlations with clinical features, including regional disability, clinical upper motor neuron signs and cognitive impairment. Patients were offered 6-monthly follow-up MRI, and the last available scan was used for a separate longitudinal analysis (n = 27). In cross-sectional study, the core signature of white matter pathology was confirmed within the corticospinal tract and callosal body, and linked strongly to clinical upper motor neuron burden, but also to limb disability subscore and progression rate. Localized grey matter abnormalities were detected in a topographically appropriate region of the left motor cortex in relation to bulbar disability, and in Broca's area and its homologue in relation to verbal fluency. Longitudinal analysis revealed progressive and widespread changes in the grey matter, notably including the basal ganglia. In contrast there was limited white matter pathology progression, in keeping with a previously unrecognized limited change in individual clinical upper motor neuron scores, despite advancing disability. Although a consistent core white matter pathology was found cross-sectionally, grey matter pathology was dominant longitudinally, and included progression in clinically silent areas such as the basal ganglia, believed to reflect their wider cortical connectivity. Such changes were significant across a range of apparently sporadic patients rather than being a genotype-specific effect. It is also suggested that the upper motor neuron lesion in amyotrophic lateral sclerosis may be relatively constant during the established symptomatic period. These findings have implications for the development of effective diagnostic versus therapeutic monitoring magnetic resonance imaging biomarkers. Amyotrophic lateral sclerosis may be characterized initially by a predominantly white matter tract pathological signature, evolving as a widespread cortical network degeneration.","Amyotrophic Lateral Sclerosis/ diagnosis;Cerebral Cortex/ pathology;Cohort Studies;Cross-Sectional Studies;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology","Menke, R. A.;Korner, S.;Filippini, N.;Douaud, G.;Knight, S.;Talbot, K.;Turner, M. R.",2014,Sep,10.1093/brain/awu162,0,
2536,Correlation between cognitive function and the association fibers in patients with Alzheimer's disease using diffusion tensor imaging,"White matter (WM) changes, along with well-characterized cortical abnormalities, occur in patients with Alzheimer's disease (AD). We investigated the integrity of WM tracts within association fibers by the use of fractional anisotropy (FA), and the relationship between FA values and cognitive function in patients with AD. Neuropsychological examination and conventional MRI, as well as diffusion tensor imaging, (DTI) were conducted on 12 patients with mild to moderate AD and 18 cognitively healthy volunteers. DTI was performed to measure FA in the bilateral inferior fronto-occipital fasciculus (IFOF) and the superior longitudinal fasciculus (SLF). Mini-Mental State Examination (MMSE) scores and Montreal Cognitive Assessment (MoCA) values were used to evaluate cognitive function and the Clinical Dementia Rating (CDR) scale was used as a staging tool for dementia severity. FA measures were analyzed and correlated with neuropsychological data. No patient showed any WM tract abnormality on either T1-weighted or T2-weighted MRI. However, the FA values in the bilateral IFOF and SLF and the MoCA scores in patients with AD were significantly decreased (p<0.05) compared to the controls. Furthermore, the decreased FA values in the SLF were positively correlated with cognitive function (MMSE scores - right: r=0.672, p=0.033, left: r=0.919, p<0.01; MoCA values - right: r=0.747, p=0.013, left: r=0.679, p=0.031). Our findings confirmed that the loss of integrity of microstructural WM connectivity has a role in the cognitive decline of patients with AD. The data also suggest that the FA values of the SLF may be used as a clinical marker of cognitive function.","Alzheimer Disease/complications/ pathology;Anisotropy;Brain/ pathology;Cognition;Cognition Disorders/etiology/ pathology;Diffusion Magnetic Resonance Imaging;Humans;Image Interpretation, Computer-Assisted;Nerve Fibers/ pathology;Neural Pathways/ pathology;Neuropsychological Tests","Meng, J. Z.;Guo, L. W.;Cheng, H.;Chen, Y. J.;Fang, L.;Qi, M.;Jia, Z. Y.;Mohammed, W.;Hong, X. N.",2012,Dec,10.1016/j.jocn.2011.12.031,0,
2537,[A study on the relation between cerebral lesion and cognitive defect in multi-infarct patients],"240 cases of multi-infarct patients with more than two cerebral infarct lesions in CT findings were collected successively from 1991 to 1992. 42.92% of them were shown to have cognitive defect with a series of neuropsychological tests. Correlation of the occurrence of cognitive defect with the CT findings such as the location and extent of focal lesions as well as the presence of cerebral atrophy or subcortical degeneration were carried out. According to the results by multiple regression and factor analysis, the location and extent of the focal infarct lesions were not the primary determining factor for the occurrence of cognitive defect. It is, therefore, suggested that the term of ischemic or vascular dementia be used clinically instead of the so-called multi-infarct dementia.","Adult;Aged;Aged, 80 and over;Atrophy;Brain/*pathology/radiography;*Cognition;Dementia, Multi-Infarct/pathology/*psychology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Prospective Studies;Regression Analysis","Meng, J. M.;Meng, C.;Yang, P. J.",1994,May,,0,
2538,Lesion Topography and Microscopic White Matter Tract Damage Contribute to Cognitive Impairment in Symptomatic Carotid Artery Disease,"Purpose To investigate associations between neuroimaging markers of cerebrovascular disease, including lesion topography and extent and severity of strategic and global cerebral tissue injury, and cognition in carotid artery disease (CAD). Materials and Methods All participants gave written informed consent to undergo brain magnetic resonance imaging and the Addenbrooke's Cognitive Examination-Revised. One hundred eight patients with symptomatic CAD but no dementia were included, and a score less than 82 represented cognitive impairment. Group comparison and interrelations between global cognitive and fluency performance, lesion topography, and ultrastructural damage were assessed with voxel-based statistics. Associations between cognition, medial temporal lobe atrophy (MTA), lesion volumes, and global white matter ultrastructural damage indexed as increased mean diffusivity were tested with regression analysis by controlling for age. Diagnostic accuracy of imaging markers selected from a multivariate prediction model was tested with receiver operating characteristic analysis. Results Cognitively impaired patients (n = 53 [49.1%], classified as having probable vascular cognitive disorder) were older than nonimpaired patients (P = .027) and had more frequent MTA (P < .001), more cortical infarctions (P = .016), and larger volumes of acute (P = .028) and chronic (P = .009) subcortical ischemic lesions. Lesion volumes did not correlate with global cognitive performance (lacunar infarctions, P = .060; acute lesions, P = .088; chronic subcortical ischemic lesions, P = .085). In contrast, cognitive performance correlated with presence of chronic ischemic lesions within the interhemispheric tracts and thalamic radiation (P < .05, false discovery rate corrected). Skeleton mean diffusivity showed the closest correlation with cognition (R(2) = 0.311, P < .001) and promising diagnostic accuracy for vascular cognitive disorder (area under the curve, 0.82 [95% confidence interval: 0.75, 0.90]). Findings were confirmed in subjects with a low risk of preclinical Alzheimer disease indexed by the absence of MTA (n = 85). Conclusion Subcortical white matter ischemic lesion locations and severity of ultrastructural tract damage contribute to cognitive impairment in symptomatic CAD, which suggests that subcortical disconnection within large-scale cognitive neural networks is a key mechanism of vascular cognitive disorder. Online supplemental material is available for this article.","Aged;Carotid Artery Diseases/ complications/ diagnostic imaging;Cerebrovascular Disorders/ diagnostic imaging/ etiology;Cognitive Dysfunction/ diagnostic imaging/ etiology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Reproducibility of Results;Risk Factors;White Matter/ pathology","Meng, D.;Hosseini, A. A.;Simpson, R. J.;Shaikh, Q.;Tench, C. R.;Dineen, R. A.;Auer, D. P.",2017,Feb,,0,
2539,Lesion Topography and Microscopic White Matter Tract Damage Contribute to Cognitive Impairment in Symptomatic Carotid Artery Disease,"Purpose To investigate associations between neuroimaging markers of cerebrovascular disease, including lesion topography and extent and severity of strategic and global cerebral tissue injury, and cognition in carotid artery disease (CAD). Materials and Methods All participants gave written informed consent to undergo brain magnetic resonance imaging and the Addenbrooke's Cognitive Examination-Revised. One hundred eight patients with symptomatic CAD but no dementia were included, and a score less than 82 represented cognitive impairment. Group comparison and interrelations between global cognitive and fluency performance, lesion topography, and ultrastructural damage were assessed with voxel-based statistics. Associations between cognition, medial temporal lobe atrophy (MTA), lesion volumes, and global white matter ultrastructural damage indexed as increased mean diffusivity were tested with regression analysis by controlling for age. Diagnostic accuracy of imaging markers selected from a multivariate prediction model was tested with receiver operating characteristic analysis. Results Cognitively impaired patients (n = 53 [49.1%], classified as having probable vascular cognitive disorder) were older than nonimpaired patients (P = .027) and had more frequent MTA (P < .001), more cortical infarctions (P = .016), and larger volumes of acute (P = .028) and chronic (P = .009) subcortical ischemic lesions. Lesion volumes did not correlate with global cognitive performance (lacunar infarctions, P = .060; acute lesions, P = .088; chronic subcortical ischemic lesions, P = .085). In contrast, cognitive performance correlated with presence of chronic ischemic lesions within the interhemispheric tracts and thalamic radiation (P < .05, false discovery rate corrected). Skeleton mean diffusivity showed the closest correlation with cognition (R2 = 0.311, P < .001) and promising diagnostic accuracy for vascular cognitive disorder (area under the curve, 0.82 [95% confidence interval: 0.75, 0.90]). Findings were confirmed in subjects with a low risk of preclinical Alzheimer disease indexed by the absence of MTA (n = 85). Conclusion Subcortical white matter ischemic lesion locations and severity of ultrastructural tract damage contribute to cognitive impairment in symptomatic CAD, which suggests that subcortical disconnection within large-scale cognitive neural networks is a key mechanism of vascular cognitive disorder. Online supplemental material is available for this article.",,"Meng, D.;Hosseini, A. A.;Simpson, R. J.;Shaikh, Q.;Tench, C. R.;Dineen, R. A.;Auer, D. P.",2016,Sep 6,10.1148/radiol.2016152685,0,2538
2540,A radiological approach to the systemic and neurologic features of hyperparathyroidism,"Parathyroid hormone (PTH) affects the nervous system directly and indirectly. The induced pathology may present typical imaging findings in neuroradiology. The hormone controls the physiological level of blood calcium. Increased serum PTH causes pathological features in the kidneys and especially in the skeleton where most calcium is situated. Primary hyperparathyroidism is due to hyperplasia or to adenomatous or carcinomatous degeneration of glandular tissue. It causes relapsing nephrolithiasis and, more seldon, nephrocalcinosis. Bone shows increased osteoclastic activity with various aspects of diffuse demineralization. In severe cases pathological fractures and sub-periosteal, sub-chondral reabsorptions appear, especially at the tendon and capsulo-ligamentous insertions. In even more severe disease fibrous osseous cysts and brown tumours may be found in bone. In the central nervous system, clinical symptoms, such as mental confusion, lethargy and exceptionally coma may appear. Radiologically, bone resorption can be observed in the skull as microlacunar confluent osteolysis (salt and pepper skull). Body fractures may develop in the spine. Secondary hyperparathyroidism is due principally to renal failure. Both hypocalcaemia and hyperphosphoraemia cause the hormone secretion increase. In this case other pathologic features are associated with the typical manifestations of primary hyperparathyroidism. The uraemic kidney is inable to synthetize active vitamin D, leading to rickets in the young and osteomalacia in adults. Hyperphosphoraemia causes ectopic periarticular calcifications. Furthermore, the lack of degradation of an endogenous protein (beta 2 microglobulin) by the kidney and its poor elimination by dialytic treatment cause chronic retention and consequent systemic amyloidosis which induces intraosseous cystic lesions and severe destructive arthropathy. All these aspects, together, are known as renal osteodystrophy. The radiological features of secondary hyperparathyroidism are the same as those observed in the primary form. In addition, all the lesions of renal osteodystrophy may be associated, further worsening the disease. In the secondary form, mild hypocalcaemia, if present, rarely leads to the neurological manifestations of the primary disease. Frequently carpal tunnel syndrome arises due to local amyloid infarction. Chronic aluminium retention may produce neurological aspects of dementia. Finally, the decrease of PTH hormone blood levels, as in hypoparathyroidism and the consequent hypocalcaemia may determine neurologic symptoms such as paresthaesias, and in severe disease, tetanic contractions. Radiologically, typical micronodular calcifications can be observed in the brain basal ganglia.",,"Meneghello, A.;Bertoli, M.",1997,1997,,0,
2541,Multiple dural arteriovenous fistulas presenting as rapidly progressive dementia,"INTRODUCTION: Dural arteriovenous fistulas (DAVFs) are important causes of neurological dysfunction and are many times misdiagnosed. Particularly in older populations, DAVFs may present with a selective cognitive dysfunction. CASE REPORT: The authors describe a 70-year-old woman presenting with a rapidly progressive dementia, very similar in presentation to prion disease. Neuroimaging showed multifocal DAVFs associated with venous thrombosis and white matter changes, suggesting that impaired cerebral circulation due to venous hypertensive encephalopathy caused the patient's dementia. Prompt treatment of some of the abnormal shunts with endovascular embolization resulted in a clinically relevant improvement. Subsequent clinical improvement was achieved with anticoagulation, although no cause or predisposing factor was documented that could have led to the development of the venous thrombosis. CONCLUSIONS: Neurologists should maintain a high degree of suspicion to avoid missing the diagnosis of DAVFs that are potentially treatable lesions. Copyright © 2012 by Lippincott Williams & Wilkins.",enbucrilate;aged;akinetic mutism;amnesia;article;artificial embolism;attention disturbance;Babinski reflex;brain angiography;brain atrophy;capsula interna;case report;computer assisted tomography;delta rhythm;dementia;differential diagnosis;disease exacerbation;disorientation;dural arteriovenous fistula;electroencephalography;external capsule;female;flaccid paralysis;flaccid tetraparesis;follow up;gait disorder;hospital admission;human;language disability;left hemisphere;Mini Mental State Examination;myoclonus;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;occlusive cerebrovascular disease;priority journal;psychomotor disorder;right hemisphere;speech disorder;startle reflex;temporal lobe;tendon reflex;treatment outcome;turbulent flow;vein dilatation;venous congestion;venous reflux;verbal memory;white matter,"Mendonça, N.;Santos, G.;Duro, D.;MacHado, E.;Goulão, A.;Santana, I.",2012,,,0,
2542,White Matter Changes Associated with Resting Sympathetic Tone in Frontotemporal Dementia vs. Alzheimer's Disease,"BACKGROUND: Resting sympathetic tone, a measure of physiological arousal, is decreased in patients with apathy and inertia, such as those with behavioral variant frontotemporal dementia (bvFTD) and other frontally-predominant disorders. OBJECTIVE: To identify the neuroanatomical correlates of skin conductance levels (SCLs), an index of resting sympathetic tone and apathy, among patients with bvFTD, where SCLs is decreased, compared to those with Alzheimer's disease (AD), where it is not. METHODS: This study analyzed bvFTD (n = 14) patients and a comparison group with early-onset AD (n = 19). We compared their resting SCLs with gray matter and white matter regions of interest and white matter measures of fiber integrity on magnetic resonance imaging and diffusion tensor imaging. RESULTS: As expected, bvFTD patients, compared to AD patients, had lower SCLs, which correlated with an apathy measure, and more gray matter loss and abnormalities of fiber integrity (fractional anisotropy and mean diffusivity) in frontal-anterior temporal regions. After controlling for group membership, the SCLs were significantly correlated with white matter volumes in the cingulum and inferior parietal region in the right hemisphere. CONCLUSION: Among dementia patients, SCLs, and resting sympathetic tone, may correlate with quantity of white matter, rather than with gray matter or with white matter fiber integrity. Loss of white matter volumes, especially involving a right frontoparietal network, may reflect chronic loss of cortical axons that mediate frontal control of resting sympathetic tone, changes that could contribute to the apathy and inertia of bvFTD and related disorders.",,"Mendez, M. F.;Joshi, A.;Daianu, M.;Jimenez, E.;Thompson, P.",2015,,10.1371/journal.pone.0142445,0,
2543,MRI hydrographic 3D sequences in CADASIL,"Two patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (figure), evolving with cognitive deterioration, had MRI. Hydrographic 3D high-resolution turbo spin-echo (TSE) with variable flip angle sequence (SPACE) was performed to demonstrate the subcortical lacunar lesions (SLL) (figure, A and B), considered specific in CADASIL.(1.)","CADASIL/complications/*diagnosis;Cognition Disorders/diagnosis/etiology;Humans;*Imaging, Three-Dimensional;*Magnetic Resonance Imaging","Mendes Coelho, V. C.;Bertholdo, D.;Ono, S. E.;de Carvalho Neto, A.",2014,Jan 28,10.1212/wnl.0000000000000056,0,
2544,[Clinical autosomal dominating arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)] Kliniczna autosomalnie dominujaca arteriopatia mozgowa z udarami podkorowymi i leukoencefalopatia (CADASIL),"CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a diffuse disease of small arteries, predominating in the brain. It starts during mid-adulthood and is characterized by recurrent ischaemic events (transient or permanent), attacks of migraine with aura, severe mood disorders, subcortical dementia and at MRI white periventricular leukoencephalopathy. CADASIL is an autosomal dominant disease. The gene Notch3 on which the mutation was detected is located on chromosome 19. There is so far no specific treatment and death occurs after a mean of twenty years.","Adult;Aged;Brain/pathology;Chromosome Aberrations/genetics;Chromosome Disorders;Chromosomes, Human, Pair 19/genetics;Dementia, Multi-Infarct/ diagnosis/genetics;Female;Gene Expression/genetics;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Point Mutation/genetics;Tomography, X-Ray Computed","Mendel, T.;Czlonkowska, A.",1999,Sep-Oct,,0,
2545,[Clinical autosomal dominating arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)],"CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a diffuse disease of small arteries, predominating in the brain. It starts during mid-adulthood and is characterized by recurrent ischaemic events (transient or permanent), attacks of migraine with aura, severe mood disorders, subcortical dementia and at MRI white periventricular leukoencephalopathy. CADASIL is an autosomal dominant disease. The gene Notch3 on which the mutation was detected is located on chromosome 19. There is so far no specific treatment and death occurs after a mean of twenty years.","Adult;Aged;Brain/pathology;Chromosome Aberrations/genetics;Chromosome Disorders;Chromosomes, Human, Pair 19/genetics;Dementia, Multi-Infarct/*diagnosis/genetics;Female;Gene Expression/genetics;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Point Mutation/genetics;Tomography, X-Ray Computed","Mendel, T.;Czlonkowska, A.",1999,Sep-Oct,,0,
2546,Complications of severe cerebral amyloid angiopathy in the course of dementia with Lewy bodies. A case report,"A 68-year-old male who suffered from dementia, progressing for four months without Parkinson's symptoms, was admitted to the Department of Neurology because of vertigo, slight left hand paresis and positive Romberg test. During hospitalization the patient's status deteriorated. The intracerebral lobar haemorrhage, subarachnoid haemorrhage and ischaemic lesions observed on CT scans suggested the clinical diagnosis of CAA. He died after 53 days due to pneumonia. On macroscopic examination, the brain showed general cortical atrophy and ventricular dilatation. Frontal lobar haemorrhage and focal subarachnoid haemorrhage were seen on the brain autopsy. Microscopic observation demonstrated neuronal loss and microspongiosis in the hippocampus, severe neuronal loss and depigmentation in the substantia nigra pars compacta and locus coeruleus. Lewy bodies were visible in the substantia nigra and amyloid angiopathy, predominantly severe CAA according to the Vonsattel scale, in the meningeal and cortical vessels. In the presented case, the microscopic findings were typical for DLB with concomitant severe CAA. In progressive dementia, neurological deterioration, presence of lobar hemorrhagic infarcts and ischaemic lesions suggest CAA coexistent with DLB and/or AD.",aged;anamnesis;angiography;article;brain hemorrhage;brain ischemia;case report;cell loss;computer assisted tomography;dementia;depigmentation;disease course;disease severity;facial nerve paralysis;hippocampus;human;Lewy body;locus ceruleus;male;paresis;pneumonia;subarachnoid hemorrhage;substantia nigra pars compacta;vascular amyloidosis;vertigo,"Mendel, T.;Bertrand, E.;Szpak, G. M.;Stȩpień, T.;Wierzba-Bobrowicz, T.",2010,,,0,
2547,White matter microstructure deteriorates across cognitive stages in Parkinson disease,"OBJECTIVES: To characterize different stages of Parkinson disease (PD)-related cognitive decline using diffusion tensor imaging (DTI) and investigate potential relationships between cognition and microstructural integrity of primary white matter tracts. METHODS: Movement Disorder Society criteria were used to classify 109 patients with PD as having normal cognition (PD-N, n = 63), mild cognitive impairment (PD-MCI, n = 28), or dementia (PD-D, n = 18), and were compared with 32 matched controls. DTI indices were assessed across groups using tract-based spatial statistics, and multiple regression was used to assess association with cognitive and clinical measures. RESULTS: Relative to controls, PD-N showed some increased mean diffusivity (MD) in corpus callosum, but no significantly decreased fractional anisotropy (FA). Decreased FA and increased MD were identified in PD-MCI and PD-D relative to controls. Only small areas of difference were observed in PD-MCI and PD-D compared with PD-N, while DTI metrics did not differ significantly between PD-MCI and PD-D. Executive function, attention, memory, and a composite measure of global cognition were associated with MD, primarily in anterior white matter tracts; only attention was associated with FA. These differences were independent of white matter hyperintensity load, which was also associated with cognition in PD. CONCLUSIONS: PD is associated with spatially restricted loss of microstructural white matter integrity in patients with relatively normal cognition, and these alterations increase with cognitive dysfunction. Functional impairment in executive function, attention, and learning and memory appears associated with microstructural changes, suggesting that tract-based spatial statistics provides an early marker for clinically relevant cognitive impairment in PD.","Aged;Aged, 80 and over;Cognition Disorders/ diagnosis/ epidemiology/psychology;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/ diagnosis/ epidemiology/psychology","Melzer, T. R.;Watts, R.;MacAskill, M. R.;Pitcher, T. L.;Livingston, L.;Keenan, R. J.;Dalrymple-Alford, J. C.;Anderson, T. J.",2013,May 14,10.1212/WNL.0b013e3182929f62,0,
2548,Tracking Parkinson's Disease over One Year with Multimodal Magnetic Resonance Imaging in a Group of Older Patients with Moderate Disease,"BACKGROUND & OBJECTIVES: Cross-sectional magnetic resonance imaging (MRI) suggests that Parkinson's disease (PD) is associated with changes in cerebral tissue volume, diffusion tensor imaging metrics, and perfusion values. Here, we performed a longitudinal multimodal MRI study--including structural, diffusion tensor imaging (DTI), and perfusion MRI--to investigate progressive brain changes over one year in a group of older PD patients at a moderate stage of disease. METHODS: Twenty-three non-demented PD (mean age (SD) = 69.5 (6.4) years, disease duration (SD) = 5.6 (4.3) years) and 23 matched control participants (mean age: 70.6 (6.8)) completed extensive neuropsychological and clinical assessment, and multimodal 3T MRI scanning at baseline and one year later. We used a voxel-based approach to assess change over time and group-by-time interactions for cerebral structural and perfusion metrics. RESULTS: Compared to controls, in PD participants there was localized grey matter atrophy over time in bilateral inferior and right middle temporal, and left orbito-frontal cortices. Using a voxel-based approach that focused on the centers of principal white matter tracts, the PD and control cohorts exhibited similar levels of change in DTI metrics. There was no significant change in perfusion, cognitive, or motor severity measures. CONCLUSIONS: In a cohort of older, non-demented PD participants, macrostructural MRI detected atrophy in the PD group compared with the control group in temporal and orbito-frontal cortices. Changes in diffusion MRI along principal white matter tracts over one year were found, but this was not differentially affected by PD.",,"Melzer, T. R.;Myall, D. J.;MacAskill, M. R.;Pitcher, T. L.;Livingston, L.;Watts, R.;Keenan, R. J.;Dalrymple-Alford, J. C.;Anderson, T. J.",2015,,10.1371/journal.pone.0143923,0,
2549,Multiple loci influencing hippocampal degeneration identified by genome scan,"OBJECTIVE: Large genome-wide association studies (GWASs) have identified many novel genes influencing Alzheimer disease (AD) risk, but most of the genetic variance remains unexplained. We conducted a 2-stage GWAS for AD-related quantitative measures of hippocampal volume (HV), total cerebral volume (TCV), and white matter hyperintensities (WMH). METHODS: Brain magnetic resonance imaging measures of HV, TCV, and WMH were obtained from 981 Caucasian and 419 African American AD cases and their cognitively normal siblings in the MIRAGE (Multi Institutional Research in Alzheimer's Genetic Epidemiology) Study, and from 168 AD cases, 336 individuals with mild cognitive impairment, and 188 controls in the Alzheimer's Disease Neuroimaging Initiative Study. A GWAS for each trait was conducted in the 2 Caucasian data sets in stage 1. Results from the 2 data sets were combined by meta-analysis. In stage 2, 1 single nucleotide polymorphism (SNP) from each region that was nominally significant in each data set (p < 0.05) and strongly associated in both data sets (p < 1.0 x 10(-5)) was evaluated in the African American data set. RESULTS: Twenty-two markers (14 for HV, 3 for TCV, and 5 for WMH) from distinct regions met criteria for evaluation in stage 2. Novel genome-wide significant associations (p < 5.0 x 10(-8)) were attained for HV with SNPs in the APOE, F5/SELP, LHFP, and GCFC2 gene regions. All of these associations were supported by evidence in each data set. Associations with different SNPs in the same gene (p < 1 x 10(-5) in Caucasians and p < 2.2 x 10(-4) in African Americans) were also observed for PICALM with HV, SYNPR with TCV, and TTC27 with WMH. INTERPRETATION: Our study demonstrates the efficacy of endophenotypes for broadening our understanding of the genetic basis of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ genetics/pathology;Disease Progression;Female;Genetic Loci;Genetic Predisposition to Disease;Genome-Wide Association Study;Genotype;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ genetics/pathology;Nerve Degeneration/ genetics/pathology;Neuroimaging;Polymorphism, Single Nucleotide","Melville, S. A.;Buros, J.;Parrado, A. R.;Vardarajan, B.;Logue, M. W.;Shen, L.;Risacher, S. L.;Kim, S.;Jun, G.;DeCarli, C.;Lunetta, K. L.;Baldwin, C. T.;Saykin, A. J.;Farrer, L. A.",2012,Jul,10.1002/ana.23644,0,
2550,AIDS-related MR hyperintensity of the basal ganglia,"PURPOSE: Our goal was to describe the MR imaging appearance and clinical pathologic correlates of bilateral basal ganglia hyperintensity in acquired immunodeficiency syndrome (AIDS). METHODS: Medical records and laboratory data were reviewed retrospectively in nine cases of bilateral basal ganglia hyperintensity on long-repetition-time MR images. Opportunistic infections of the central nervous system were excluded by clinical and laboratory data. Postmortem neuropathologic examination was obtained in two cases. RESULTS: All patients presented acutely with new seizures or changes in mental status. A history of drug abuse was elicited in seven of the nine remaining patients. Renal failure was present in six cases. Symmetric bilateral caudate and putamen hyperintensity on T2-weighted images was found in all cases with variable extension to the surrounding white matter, thalamus, and brain stem. Postmortem neuropathologic examination in two cases revealed numerous microinfarcts in a distribution similar to the MR signal abnormalities. CONCLUSION: The MR appearance of basal ganglia hyperintensity in this series of AIDS patients represents ischemic tissue injury. We propose that this clinicopathologic entity is precipitated by the combined effects of human immunodeficiency virus infection and drug use, particularly cocaine and/or associated toxic contaminants.",AIDS Dementia Complex/ diagnosis/pathology;Adult;Basal Ganglia/ pathology;Cocaine;Female;Humans;Magnetic Resonance Imaging;Male;Retrospective Studies;Substance-Related Disorders,"Meltzer, C. C.;Wells, S. W.;Becher, M. W.;Flanigan, K. M.;Oyler, G. A.;Lee, R. R.",1998,Jan,,0,
2551,Comparative evaluation of MR-based partial-volume correction schemes for PET,"Because of limitations of spatial resolution, quantitative PET measurements of cerebral blood flow, glucose metabolism and neuroreceptor binding are influenced by partial-volume averaging among neighboring tissues with differing tracer concentrations. METHODS: Two MR-based approaches to partial-volume correction of PET images were compared using simulations and a multicompartment phantom. The two-compartment method corrects PET data for the diluting effects of cerebrospinal fluid (CSF) spaces. The more complex three-compartment method also accounts for the effect of partial-volume averaging between gray and white matter. The effects of the most significant sources of error on MR-based partial-volume correction, including misregistration, resolution mismatch, segmentation errors and white matter heterogeneity, were evaluated. We also examined the relative usefulness of both approaches in PET studies of aging and neurodegenerative disease. RESULTS: Although the three-compartment method was highly accurate (with 100% gray matter recovery achieved in simulations), it was also more sensitive to all errors tested, particularly image segmentation and PET-MR registration. CONCLUSION: Based on these data, we conclude that the two-compartment approach is better suited for comparative PET studies, whereas the three-compartment algorithm is capable of greater accuracy for absolute quantitative measures.","Aging;Alzheimer Disease/pathology/radionuclide imaging;Brain/anatomy & histology/pathology/ radionuclide imaging;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Phantoms, Imaging;Tomography, Emission-Computed","Meltzer, C. C.;Kinahan, P. E.;Greer, P. J.;Nichols, T. E.;Comtat, C.;Cantwell, M. N.;Lin, M. P.;Price, J. C.",1999,Dec,,0,
2552,SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only,"OBJECTIVE: We describe the clinical, molecular, genetic, MRI, and SPECT features of a German family with autosomal dominant migraine and dementia, mapping to the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) locus. We studied the correlation of cerebral blood flow, MRI, and cognitive function. BACKGROUND: CADASIL is a small-vessel disease of the brain mapped to chromosome 19p13.1. Mutations of the Notch3 gene cause this disorder. Most phenotypes are characterized by transient ischemic attacks (TIAs) and lacunar strokes leading to dementia. Migraine is frequent. A single photon emission computed tomographic (SPECT) study of this disorder has not yet been published. METHODS: We studied 13 individuals clinically and performed neuroimaging studies with MRI and SPECT. RESULTS: Genetic analysis strongly supported linkage to the CADASIL locus, and the disease haplotype was found in six individuals. Analysis by single-strand confirmation polymorphism did not identify Notch3 mutations. All affected individuals had MRI white matter hyperintensities and four individuals had additional basal ganglial signal abnormalities. Four affected individuals had migraine, two of whom had slowly progressive dementia. TIAs, stroke, and focal neurologic signs were absent. Cerebral blood flow reduction in SPECT studies of affected individuals matched with MRI signal abnormalities. Cognitive impairment was linked to signal abnormalities and hypoperfusion in the basal ganglia. Demented patients had a pattern of frontal, temporal, and basal ganglial hypoperfusion. CONCLUSIONS: We describe a CADASIL phenotype that is characterized by the absence of focal neurologic symptoms and present the first SPECT study of this disorder.","Adolescent;Adult;Brain Diseases/diagnosis/*genetics/physiopathology;Cerebral Arterial Diseases/diagnosis/*genetics/physiopathology;Cerebral Infarction/diagnosis/*genetics/physiopathology;Cerebrovascular Circulation/physiology;Dementia/genetics/pathology/psychology;Disease Progression;Female;*Genes, Dominant;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Migraine Disorders/genetics;Neuropsychological Tests;Pedigree;Phenotype;Skin/pathology;*Tomography, Emission-Computed, Single-Photon","Mellies, J. K.;Baumer, T.;Muller, J. A.;Tournier-Lasserve, E.;Chabriat, H.;Knobloch, O.;Hackeloer, H. J.;Goebel, H. H.;Wetzig, L.;Haller, P.",1998,Jun,,0,
2553,Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease,"BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-beta (Abeta). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. OBJECTIVE: To determine whether neuroinflammation exacerbates neural damage in preclinical AD. METHODS: We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Abeta42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. RESULTS: Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Abeta42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. CONCLUSION: Inflammation may play a role in neural damage in preclinical AD.",,"Melah, K. E.;Lu, S. Y.;Hoscheidt, S. M.;Alexander, A. L.;Adluru, N.;Destiche, D. J.;Carlsson, C. M.;Zetterberg, H.;Blennow, K.;Okonkwo, O. C.;Gleason, C. E.;Dowling, N. M.;Bratzke, L. C.;Rowley, H. A.;Sager, M. A.;Asthana, S.;Johnson, S. C.;Bendlin, B. B.",2016,Jan 22,10.3233/jad-150897,0,
2554,Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia,"Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally- with a slight predilection for the right- in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.",Behavioral variant frontotemporal dementia;diffusion tensor imaging;functional connectivity;lateralization;resting state functional MRI;semantic dementia;white matter microstructure,"Meijboom, R.;Steketee, R. M.;Ham, L. S.;van der Lugt, A.;van Swieten, J. C.;Smits, M.",2017,,,0,
2555,Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia,"OBJECTIVES: Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. METHODS: Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. RESULTS: PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. CONCLUSIONS: Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. KEY POINTS: * PhFTD shows brain abnormalities that are similar to bvFTD. * PhFTD shows increased functional connectivity in the parietal default mode network. * PhFTD shows microstructural white matter abnormalities in the frontal lobe. * We hypothesise phFTD and bvFTD may belong to the same disease spectrum.",Adult;Aged;Diffusion Tensor Imaging/methods;Disease Progression;Female;Frontotemporal Dementia/ diagnostic imaging/ pathology;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Netherlands;White Matter/ diagnostic imaging/ pathology;Diagnosis;Diffusion tensor imaging;Frontotemporal dementia;Functional magnetic resonance imaging;White matter,"Meijboom, R.;Steketee, R. M.;de Koning, I.;Osse, R. J.;Jiskoot, L. C.;de Jong, F. J.;van der Lugt, A.;van Swieten, J. C.;Smits, M.",2017,Apr,,0,2556
2556,Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia,"OBJECTIVES: Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. METHODS: Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. RESULTS: PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. CONCLUSIONS: Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. KEY POINTS: * PhFTD shows brain abnormalities that are similar to bvFTD. * PhFTD shows increased functional connectivity in the parietal default mode network. * PhFTD shows microstructural white matter abnormalities in the frontal lobe. * We hypothesise phFTD and bvFTD may belong to the same disease spectrum.",Diagnosis;Diffusion tensor imaging;Frontotemporal dementia;Functional magnetic resonance imaging;White matter,"Meijboom, R.;Steketee, R. M.;de Koning, I.;Osse, R. J.;Jiskoot, L. C.;de Jong, F. J.;van der Lugt, A.;van Swieten, J. C.;Smits, M.",2016,Jul 19,10.1007/s00330-016-4490-4,0,
2557,White matter predictors of cognitive functioning in older adults,"Few studies have applied multiple imaging modalities to examine cognitive correlates of white matter. We examined the utility of T2-weighted magnetic resonance imaging (MRI) -derived white matter hyperintensities (WMH) and diffusion tensor imaging-derived fractional anisotropy (FA) to predict cognitive functioning among older adults. Quantitative MRI and neuropsychological evaluations were performed in 112 older participants from an ongoing study of the genetics of Alzheimer's disease (AD) in African Americans. Regional WMH volumes and FA were measured in multiple regions of interest. We examined the association of regional WMH and an FA summary score with cognitive test performance. Differences in WMH and FA were compared across diagnostic groups (i.e., normal controls, mild cognitive impairment, and probable AD). Increased WMH volume in frontal lobes was associated with poorer delayed memory performance. FA did not emerge as a significant predictor of cognition. White matter hyperintensity volume in the frontal and parietal lobes was increased in MCI participants and more so in AD patients relative to controls. These results highlight the importance of regionally distributed small vessel cerebrovascular disease in memory performance and AD among African American older adults. White matter microstructural changes, quantified with diffusion tensor imaging, appear to play a lesser role in our sample.","African Americans;Aged;Aged, 80 and over;Alzheimer Disease/ complications/ pathology;Analysis of Variance;Anisotropy;Diffusion Magnetic Resonance Imaging;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Statistics, Nonparametric","Meier, I. B.;Manly, J. J.;Provenzano, F. A.;Louie, K. S.;Wasserman, B. T.;Griffith, E. Y.;Hector, J. T.;Allocco, E.;Brickman, A. M.",2012,May,10.1017/s1355617712000227,0,
2558,Lobar microbleeds are associated with a decline in executive functioning in older adults,"BACKGROUND: Normal aging is associated with a decline in cognitive abilities, particularly in the domains of psychomotor speed and executive functioning. However, 'aging,' per se, is not a cause of cognitive decline but rather a variable that likely captures multiple accumulating biological changes over time that collectively affect mental abilities. Recent work has focused on the role of cerebrovascular disease as one of the biological changes. In the current study, we examined whether lobar microbleeds - magnetic resonance imaging (MRI) signal voids due to hemosiderin deposits secondary to cerebral amyloid angiopathy - are associated with cognitive decline in normal aging. Previous studies that reported a relationship between the presence of lobar microbleeds and decreased cognitive abilities have been primarily cross-sectional. Here, we used a retrospective longitudinal design to examine whether the presence of lobar microbleeds is associated with the rate of cognitive decline among non-demented older adults. METHODS: Participants came from an ongoing longitudinal community-based aging study, in which subjects are evaluated at 18-24 months intervals and received a full medical, neurological, and neuropsychological examination at each of the follow-up visits. Gradient echo MRI scans were available on 197 non-demented participants (mean age: 84.15 +/- 5.02 years). Microbleeds were rated visually on axial view and divided into subcortical (basal ganglia, cerebellum) and lobar (frontal, temporal, parietal, occipital lobe) regions, and confirmed with coronal and sagittal views to exclude artifacts. Cognition was assessed with a neuropsychological battery, providing summary scores for memory, language, executive, and visuospatial abilities. Using general estimating equations (GEE), we compared cognition cross-sectionally between individuals with 2 or more (n = 11) and fewer than 2 (n = 186) lobar microbleeds and examined longitudinal cognitive change beginning 9.47 +/- 3.13 years before the MRI scan. RESULTS: Subjects with 2 or more lobar microbleeds had worse executive functioning at the visit closest to the MRI scan (beta = -0.044; p < 0.001) and had a faster decline in executive function over time (beta = -0.072; p = 0.012) than subjects with fewer than 2 lobar microbleeds. The two groups were similar in age at scan date, education, ethnicity, sex distribution, and cognitive performance at first visit. CONCLUSIONS: Lobar microbleeds, a marker of cerebral amyloid angiopathy, are associated with an accelerated rate of executive function decline. The presence of cerebral amyloid angiopathy may be an important source of cognitive decline in aging. Future work should examine how cerebral amyloid angiopathy interacts with neurodegenerative processes, such as Alzheimer's disease.","Adult;Aged;Aged, 80 and over;Aging;Cerebral Amyloid Angiopathy/ etiology;Cognition/physiology;Cognition Disorders/ etiology;Cross-Sectional Studies;Executive Function/ physiology;Female;Humans;Intracranial Hemorrhages/ complications;Magnetic Resonance Imaging/methods;Male;Memory/physiology;Middle Aged;Neuropsychological Tests;Retrospective Studies","Meier, I. B.;Gu, Y.;Guzaman, V. A.;Wiegman, A. F.;Schupf, N.;Manly, J. J.;Luchsinger, J. A.;Viswanathan, A.;Martinez-Ramirez, S.;Greenberg, S. M.;Mayeux, R.;Brickman, A. M.",2014,,10.1159/000368998,0,
2559,Spontaneous cerebellar hemorrhage associated with a novel Notch3 mutation,"A 55-year-old woman with no significant medical history presented with an acute onset severe headache. A non-enhanced CT scan of the head revealed a right cerebellar hemorrhage. Investigation for etiology of the hemorrhage included an MRI showing extensive subcortical ischemic disease and also several previous microbleeds. The MRI appearance and absence of any other etiology for hemorrhage prompted work up for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). She was found to have a guanosine to thymidine transversion at nucleotide position 1336, codon position 420, resulting in a glycine > cysteine substitution interpreted as ""predicted CADASIL-associated mutation"". To our knowledge, this mutation has not yet been reported in association with CADASIL. © 2013 Elsevier Ltd. All rights reserved.",Notch3 receptor;adult;amino acid substitution;article;CADASIL;case report;cerebellum hemorrhage;codon;computer assisted tomography;exon;female;gene identification;gene mutation;genetic association;genetic screening;headache;human;human tissue;mutational analysis;Notch3 gene;nuclear magnetic resonance imaging;polymerase chain reaction;priority journal;skin biopsy,"Mehta, S.;Mehndiratta, P.;Sila, C. A.",2013,,,0,
2560,"Recurrent delusional ideas due to left caudate head infarction, without dementia","Herein we report the case of a 77-year-old, right-handed man, without dementia, who had a cerebral infarction in the left caudate head that manifested recurrent delusional ideas. He experienced three episodes of delusional ideas; the first two occurred after loss of consciousness and the third after delirium at night. MRI findings of left caudate head infarction were the same for all three episodes. An unstable cerebral perfusion may have caused problems in the cerebral network between the caudate head and cerebral cortex. Decreased cerebral blood flow in the frontal lobe was noted particularly in the second and third episodes, supporting the neurological background of disinhibition of emotional behaviour. Antipsychotic drugs and a small dose of risperidone were effective in controlling the patient's delusional ideas. © 2012 The Authors. Psychogeriatrics © 2012 Japanese Psychogeriatric Society.",antithrombocytic agent;risperidone;aged;article;brain blood flow;brain cortex;brain infarction;brain perfusion;case report;caudate nucleus;computer assisted tomography;delirium;delusion;dementia;disease duration;emotion;episodic memory;frontal lobe;human;long term memory;male;nuclear magnetic resonance imaging;priority journal;recurrent disease;sexual behavior;single photon emission computer tomography;unconsciousness,"Meguro, K.;Meguro, M.;Akanuma, K.",2012,,,0,
2561,A clinicopathological study of senile dementia of Alzheimer's type (SDAT) and white matter lesions of Binswanger's type,"A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.",aged;aging;Alzheimer disease;article;clinical trial;computer assisted tomography;controlled clinical trial;controlled study;human;major clinical study;senile dementia;white matter,"Meguro, K.;Matsushita, M.;Yoshida, R.;Otomo, E.;Yamaguchi, S.;Nakagawa, T.;Sasaki, H.",1994,,,0,
2562,"Corpus callosum atrophy, white matter lesions, and frontal executive dysfunction in normal aging and Alzheimer's disease. A community-based study: the Tajiri Project","BACKGROUND AND OBJECTIVES: Cerebral MRIs of normal aging and Alzheimer's disease (AD) frequently reveal corpus callosum (CC) atrophy, white matter hyperintensity (WMH), and hippocampal atrophy. However, their relationship or the relationship between these findings and cognitive function has not been fully studied. We investigated the relationship between CC atrophy, WMH, and hippocampal atrophy, together with frontal executive dysfunction in both normal aging and AD. METHOD: We examined 170 randomly selected residents from a designated community: 99 Clinical Dementia Rating (CDR) 0 (healthy, control group, HC) participants, 54 CDR 0.5 (very mild AD) patients, and 17 CDR 1 & 2 (probable AD) patients. By means of MRI, WMH and CC atrophy were visually rated. Four portions of the CC and the hippocampal width were measured. A Mini-Mental State Examination and Cognitive Abilities Screening Instrument (CASI) were performed to assess global function. For the frontal function, the CASI subitems of attention and word fluency, letter-based fluency, the Digit Symbol test of the WAIS-R, and Trail Making Tests were performed. RESULTS: Those patients with CDR 1 & 2 had both hippocampal and CC atrophy, whereas the CDR 0.5 patients had only hippocampal atrophy. Frontal executive dysfunction was associated with CC atrophy in both the HC and AD groups. Significant Spearman correlations were noted between CC atrophy and WMH in both groups. The combined effect of CC atrophy and WMH was noted only in the verbal fluency test in the HC group. CONCLUSION: In both groups, CC atrophy was associated with frontal executive dysfunction. The combined effect of CC atrophy and WMH in normal aging was probably due to subclinical ischemic conditions.",Aged;*Aging/pathology;Alzheimer Disease/*complications/*pathology/physiopathology;Atrophy;Cognition Disorders/*etiology/pathology/physiopathology;Corpus Callosum/*pathology;Female;Frontal Lobe/*physiopathology;Humans;Language Tests;Magnetic Resonance Imaging;Male;Speech Disorders/etiology;Trail Making Test,"Meguro, K.;Constans, J. M.;Shimada, M.;Yamaguchi, S.;Ishizaki, J.;Ishii, H.;Yamadori, A.;Sekita, Y.",2003,Mar,,0,
2563,Vascular dementia with left thalamic infarction: Neuropsychological and behavioral implications suggested by involvement of the thalamic nucleus and the remote effect on cerebral cortex. The Osaki-Tajiri project,"Vascular dementia (VaD) is a condition whereby decreased cerebral perfusion causes cognitive deterioration. We hypothesized that lesions of the anterior nucleus (AN) including the mammillo-thalamic tract cause a decline in the recollection of past episodes/events, and that the left thalamic infarction can cause frontal dysfunction through the ""diaschisis."" We investigated 18 VaD cases with only left thalamic infarction. 99mTc-ECD single photon emission computed tomography (SPECT) was used to assess regional cerebral blood flow (CBF). To test the first hypothesis, the scores on the Cognitive Abilities Screening Instrument (CASI) domain Recent memory or the rating on the Clinical Dementia Rating (CDR) domain Memory were analyzed. To test the second hypothesis, we selected the six regions of interest that correlated with the two measures, i.e., word fluency and/or depressive state, as assessed with the Geriatric Depression Scale (GDS). We found that all patients had amnesia, especially in the AN group, six of the eight patients had scores of 1+ on the CDR Memory scale, and all but one disclosed the CASI domain Recent memory impairment. There were significant correlations between the left anterior cingulate CBF and word fluency scores, and between the right rectal gyrus CBF and GDS scores. We suggest that these observations are due to a remote effect of the thalamic lesion. © 2013 Elsevier Ireland Ltd.",cysteine ethyl ester tc 99m;aged;Alzheimer disease;amnesia;anterior cingulate;article;brain blood flow;brain cortex;brain infarction;clinical article;Clinical Dementia Rating;cognition;contrast enhancement;controlled study;conversation;depression;episodic memory;female;Geriatric Depression Scale;hemiparesis;human;image analysis;image reconstruction;long term memory;major depression;male;mental deterioration;Mini Mental State Examination;multiinfarct dementia;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;prospective study;scoring system;single photon emission computer tomography;SPECT scanner;thalamus infarction;thalamus nucleus;verbal communication;word list recall;Multispect,"Meguro, K.;Akanuma, K.;Ouchi, Y.;Meguro, M.;Nakamura, K.;Yamaguchi, S.",2013,,,0,
2564,Automated brain tissue assessment in the elderly and demented population: construction and validation of a sub-volume probabilistic brain atlas,"OBJECTIVES: To develop an automated imaging assessment tool that accommodates the anatomic variability of the elderly and demented population as well as the registration errors occurring during spatial normalization. METHODS: 20 subjects with Alzheimer's disease (AD), mild cognitive impairment, or normal cognition underwent MRI brain imaging and had their 3D volumetric datasets manually partitioned into 68 regions of interest (ROI) termed sub-volumes. Gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) voxel counts were then made in the subject's native space for comparison against automated volumetric measures within three sub-volume probabilistic atlas (SVPA) models. The three SVPAs were constructed using 12 parameter affine (12 p), 2nd order (2nd), and 6th order (6th) transforms derived from registering the manually partitioned scans into a Talairach compatible AD population-based target. The three SVPA automated measures were compared to the manually derived measures in the 20 subjects' native space with a ""jack-knife"" procedure in which each subject was assessed by an SVPA they did not contribute toward constructing. RESULTS: The mean left and right GM ratio (GM ratio = [GM + CSF] / CSF) ""r values"" for the 3 SVPAs compared to the manually derived ratios across the 68 ROIs were 0.85 for the 12p SVPA, 0.88 for the 2nd SVPA, and 0.89 for the 6th SVPA. The mean left and right WM ratio (WM ratio = [WM + CSF] / CSF) ""r values"" for the 3 SVPAs being 0.84 for the 12p SVPA, 0.86 for the 2nd SVPA, and 0.88 for the 6th SVPA. CONCLUSION: We have constructed, from an elderly and demented cohort, an automated brain volumetric tool that has excellent accuracy compared to a manual gold standard and is capable of regional hypothesis testing and individual patient assessment compared to a population.","Aged;Aging/ pathology;Algorithms;Alzheimer Disease/pathology;Brain/ anatomy & histology/growth & development/ pathology;Brain Mapping/ methods;Data Interpretation, Statistical;Dementia/ pathology;Functional Laterality/physiology;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/statistics & numerical data;Parahippocampal Gyrus/growth & development/pathology;Reference Values","Mega, M. S.;Dinov, I. D.;Mazziotta, J. C.;Manese, M.;Thompson, P. M.;Lindshield, C.;Moussai, J.;Tran, N.;Olsen, K.;Zoumalan, C. I.;Woods, R. P.;Toga, A. W.",2005,Jul 15,10.1016/j.neuroimage.2005.03.031,0,
2565,Diffusion tensor imaging investigations in Alzheimer's disease: the resurgence of white matter compromise in the cortical dysfunction of the aging brain,"Diffusion tensor imaging (DTI) is a sophisticated MRI-based neuroimaging technique that enables in vivo quantification of differences in molecular diffusion at the cellular level. Owing to the highly directional architecture of white matter (WM), DTI is providing important clues of the structure and geometric organization of this neural compartment. Since DTI can detect changes even in the case of radiologically ""normal"" appearing WM, researchers are using the technique for the study of WM integrity at the initial stages of the most common neurodegenerative disorders. Along with a well characterized cortical pathology (neuritic plaques and intracellular neurofibrillary tangles), WM changes have been also demonstrated in Alzheimer's disease (AD). However, these changes had been for years found nonliable in the onset and progress of AD, basically due to lack of incriminatory evidence. The use of novel tools such as DTI has enabled the anatomical distribution of WM microstructural damage in the prodromal stages of AD to be gauged and determined, granting a long-delayed protagonic role to WM in the natural history of this highly prevalent neurodegenerative condition.",,"Medina, D. A.;Gaviria, M.",2008,Aug,,0,
2566,White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study,"Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimer's disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Cognition Disorders/ pathology;Data Interpretation, Statistical;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Infarction, Middle Cerebral Artery/pathology;Male;Middle Aged;Psychiatric Status Rating Scales","Medina, D.;DeToledo-Morrell, L.;Urresta, F.;Gabrieli, J. D.;Moseley, M.;Fleischman, D.;Bennett, D. A.;Leurgans, S.;Turner, D. A.;Stebbins, G. T.",2006,May,10.1016/j.neurobiolaging.2005.03.026,0,
2567,The thyroid hormone receptor alpha locus and white matter lesions: a role for the clock gene REV-ERBalpha,"BACKGROUND: Thyroid disorders are associated with an increased risk of cognitive impairment and Alzheimer's disease. Both small vessel disease and neurodegeneration have a role in the pathogenesis of cognitive impairment and Alzheimer's disease. Thyroid hormone receptor alpha (TRalpha) is the predominant TR in brain. The circadian clock gene REV-ERBalpha overlaps with the TRalpha gene and interferes with TRalpha expression. Limited data are available on the role of the TRalpha/REV-ERBalpha locus in small vessel disease and neurodegeneration. We therefore studied genetic variation in the TRalpha/REV-ERBalpha locus in relation to brain imaging data, as early markers for small vessel disease and neurodegeneration. METHODS: Fifteen polymorphisms, covering the TRalpha/REV-ERBalpha locus, were studied in relation to white matter lesion (WML), total brain, and hippocampal volumes in the Rotterdam Study I (RS-I, n=454). Associations that remained significant after multiple testing correction were subsequently studied in an independent population for replication (RS-II, n=607). RESULTS: No associations with total brain or hippocampal volumes were detected. A haplotype block in REV-ERBalpha was associated with WML volumes in RS-I. Absence of this haplotype was associated with larger WML volumes in women (0.38%+/-0.18% [beta+/-SE], p=0.007), but not in men (0.04%+/-0.11%, p=0.24), which was replicated in RS-II (women: 0.15%+/-0.05%, p=0.04; men: 0.05%+/-0.07%, p=0.80). Meta-analysis of the two populations showed that women lacking this haplotype have a 1.9 times larger WML volume (p=0.001). CONCLUSION: Our results suggest a role for REV-ERBalpha in the pathogenesis of WMLs.","Brain/anatomy & histology/pathology;Female;Haplotypes;Humans;Leukoencephalopathies/ genetics/pathology;Male;Middle Aged;Nuclear Receptor Subfamily 1, Group D, Member 1/ genetics/physiology;Polymorphism, Genetic;Thyroid Hormone Receptors alpha/genetics","Medici, M.;Ikram, M. A.;van der Lijn, F.;den Heijer, T.;Vernooij, M. W.;Hofman, A.;Niessen, W. J.;Visser, T. J.;Breteler, M. M.;Peeters, R. P.",2012,Nov,10.1089/thy.2012.0198,0,
2568,Subtle post-procedural cognitive dysfunction after atrial fibrillation ablation,"OBJECTIVES: This study sought to determine whether post-operative neurocognitive dysfunction (POCD) occurs after ablation for atrial fibrillation (AF). BACKGROUND: Ablation for AF is a highly effective strategy; however, the risk of transient ischemic attack and stroke is approximately 0.5% to 1%. In addition, magnetic resonance imaging studies report a 7% to 14% prevalence of silent cerebral infarction. Whether cerebral ischemia results in POCD after ablation for AF is not well established. METHODS: The study included 150 patients; 60 patients undergoing ablation for paroxysmal atrial fibrillation (PAF), 30 patients undergoing ablation for persistent atrial fibrillation (PeAF), and 30 patients undergoing ablation for supraventricular tachycardia (SVT) were compared with a matched nonoperative control group of patients with AF awaiting radiofrequency ablation (n = 30). Eight neuropsychological tests were administered at baseline and at 2 days and 90 days post-operatively. The tests were administered at the same time points to the nonoperative control group. The reliable change index was used to calculate POCD. RESULTS: The prevalences of POCD at day 2 post-procedure were 28% in patients with PAF, 27% in patients with PeAF, 13% in patients with SVT, and 0% in control patients with AF (p = 0.007). At day 90, the prevalences of POCD were 13% in patients with PAF, 20% in patients with PeAF, 3% in patients with SVT, and 0% in control patients with AF (p = 0.03). When analyzing the 3 procedural groups together, 29 of 120 patients (24%) manifested POCD at day 2 and 15 of 120 patients (13%) at day 90 post-procedure (p = 0.029). On univariate analysis, increasing left atrial access time was associated with POCD at day 2 (p = 0.04) and day 90 (p = 0.03). CONCLUSIONS: Ablation for AF is associated with a 13% to 20% prevalence of POCD in patients with AF at long-term follow-up. These results were seen in a patient population with predominant CHADS2 (Congestive heart failure, Hypertension, Age >/=75 years, Diabetes mellitus, previous Stroke/transient ischemic attack) scores of 0 to 1, representing the majority of patients undergoing ablation for AF. The long-term implications of these subtle changes require further study.","Adult;Aged;Atrial Fibrillation/classification/ surgery;Case-Control Studies;Catheter Ablation;Cognition Disorders/epidemiology/ etiology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Neuropsychological Tests;Postoperative Complications;Prevalence;Tachycardia, Supraventricular/surgery","Medi, C.;Evered, L.;Silbert, B.;Teh, A.;Halloran, K.;Morton, J.;Kistler, P.;Kalman, J.",2013,Aug 6,10.1016/j.jacc.2013.03.073,0,
2569,Brain network efficiency is influenced by the pathologic source of corticobasal syndrome,"OBJECTIVE: To apply network-based statistics to diffusion-weighted imaging tractography data and detect Alzheimer disease vs non-Alzheimer degeneration in the context of corticobasal syndrome. METHODS: In a cross-sectional design, pathology was confirmed by autopsy or a pathologically validated CSF total tau-to-beta-amyloid ratio (T-tau/Abeta). Using structural MRI data, we identify association areas in fronto-temporo-parietal cortex with reduced gray matter density in corticobasal syndrome (n = 40) relative to age-matched controls (n = 40). Using these fronto-temporo-parietal regions of interest, we construct structural brain networks in clinically similar subgroups of individuals with Alzheimer disease (n = 21) or non-Alzheimer pathology (n = 19) by linking these regions by the number of white matter streamlines identified in a deterministic tractography analysis of diffusion tensor imaging data. We characterize these structural networks using 5 graph-based statistics, and assess their relative utility in classifying underlying pathology with leave-one-out cross-validation using a supervised support vector machine. RESULTS: Gray matter density poorly discriminates between Alzheimer disease and non-Alzheimer pathology subgroups with low sensitivity (57%) and specificity (52%). In contrast, a statistic of local network efficiency demonstrates very good discriminatory power, with 85% sensitivity and 84% specificity. CONCLUSIONS: Our results indicate that the underlying pathologic sources of corticobasal syndrome can be classified more accurately using graph theoretical statistics derived from patterns of white matter network organization in association cortex than by regional gray matter density alone. These results highlight the importance of a multimodal neuroimaging approach to diagnostic analyses of corticobasal syndrome.","0 (Amyloid beta-Peptides);0 (MAPT protein, human);0 (tau Proteins);Aged;Alzheimer Disease/cerebrospinal fluid/classification/diagnostic imaging/pathology;Amyloid beta-Peptides/cerebrospinal fluid;Brain/ diagnostic imaging;Cohort Studies;Cross-Sectional Studies;Diagnosis, Differential;Diffusion Tensor Imaging;Female;Gray Matter/diagnostic imaging;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neurodegenerative Diseases/cerebrospinal fluid/ classification/ diagnostic;imaging/pathology;Sensitivity and Specificity;Support Vector Machine;Syndrome;White Matter/diagnostic imaging;tau Proteins/cerebrospinal fluid","Medaglia, J. D.;Huang, W.;Segarra, S.;Olm, C.;Gee, J.;Grossman, M.;Ribeiro, A.;McMillan, C. T.;Bassett, D. S.",2017,Sep 26,,0,
2570,"Creutzfeldt-Jakob disease, prion protein gene codon 129VV, and a novel PrPSc type in a young British woman","Background: Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease causally related to bovine spongiform encephalopathy that has occurred predominantly in young adults. All clinical cases studied have been methionine homozygotes at codon 129 of the prion protein gene (PRNP) with distinctive neuropathological findings and molecular strain type (PrPSc type 4). Modeling studies in transgenic mice suggest that other PRNP genotypes will also be susceptible to infection with bovine spongiform encephalopathy prions but may develop distinctive phenotypes. Objective: To describe the histopathologic and molecular investigation in a young British woman with atypical sporadic CJD and valine homozygosity at PRNP codon 129. Design: Case report, autopsy, and molecular analysis. Setting: Specialist neurology referral center, together with the laboratory services of the MRC [Medical Research Council] Prion Unit. Subject: Single hospitalized patient. Main Outcome Measures: Autopsy findings and molecular investigation results. Results: Autopsy findings were atypical of sporadic CJD, with marked gray and white matter degeneration and widespread prion protein (PrP) deposition. Lymphoreticular tissue was not available for analysis. Molecular analysis of PrPSc (the scrapie isoform of PrP) from cerebellar tissue demonstrated a novel PrPSc type similar to that seen in vCJD (PrPSc type 4). However, this could be distinguished from the typical vCJD pattern by an altered protease cleavage site in the presence of the metal ion chelator EDTA. Conclusions: Further studies will be required to characterize the prion strain seen in this patient and to investigate its etiologic relationship with bovine spongiform encephalopathy. This case illustrates the importance of molecular analysis of prion disease, including the use of EDTA to investigate the metal dependence of protease cleavage patterns of PrPSc. ©2007 American Medical Association. All rights reserved.",edetic acid;prion protein;proteinase;valine;adult;anamnesis;article;autopsy;case report;cerebrospinal fluid analysis;clinical examination;clinical feature;codon;Creutzfeldt Jakob disease;DNA polymorphism;electroencephalography;female;gray matter;histopathology;homozygosity;hospital patient;human;human tissue;laboratory test;nerve conduction;neuroimaging;nuclear magnetic resonance imaging;prion;priority journal;protein degradation;reticuloendothelial system;white matter,"Mead, S.;Joiner, S.;Desbruslais, M.;Beck, J. A.;O'Donoghue, M.;Lantos, P.;Wadsworth, J. D. F.;Collinge, J.",2007,,,0,
2571,"Familial British dementia with amyloid angiopathy. Early clinical, neuropsychological and imaging findings","Familial British dementia with amyloid angiopathy (FBD) is an autosomal dominant condition characterized by a dementia, progressive spastic tetraparesis and cerebellar ataxia with onset in the sixth decade. A point mutation in the BRI gene has been shown to be the genetic abnormality. Genealogical work with the large family originally reported by Worster-Drought and updated by Plant has identified nine generations dating back to the late eighteenth century. The pedigree now includes six living affected patients, 35 historical cases, and 52 descendants at risk of having inherited the disease. A common ancestor has been identified between the large pedigree and a case report of 'familial cerebellar ataxia with amyloid angiopathy'. An autopsy case from a separate family with an identical condition is described but no common ancestor with the large pedigree has been found. Case histories have been researched and updated in each pedigree. Eleven individuals at risk of FBD, aged between 44 and 56 years, agreed to undergo a clinical and neuropsychological assessment along with MRT brain imaging in order to clarify early diagnostic features. Five of the eleven were thought to show early clinical signs of the disease. Neurological examination was abnormal in three, with limb and gait ataxia and mild spastic paraparesis. Three had impaired recognition and recall memory and another had mild impairment of delayed visual recall. All affected individuals had an abnormal MRI of the brain, consisting of deep white-matter hyperintensity (T(2)-weighted scans) and lacunar infarcts, but no intracerebral haemorrhage. The corpus callosum was affected particularly, and in one patient it was severely atrophic.",,"Mead, S.;James-Galton, M.;Revesz, T.;Doshi, R. B.;Harwood, G.;Lee Pan, E.;Ghiso, J.;Frangione, B.;Plant, G.",2000,May,,0,
2572,Should computed tomography appearance of lacunar stroke influence patient management?,"Patients with a lacunar stroke syndrome may have cortical infarcts on brain imaging rather than lacunar infarcts, and patients with the clinical features of a small cortical stroke (partial anterior circulation syndrome, PACS) may have lacunar infarcts on imaging. The aim was to compare risk factors and outcome in lacunar syndrome (LACS) with cortical infarct, LACS with lacunar infarct, PACS with cortical infarct, and PACS with lacunar infarct to determine whether the clinical syndrome should be modified according to brain imaging. As part of a hospital stroke registry, patients with first ever stroke from 1990 to 1998 were assessed by a stroke physician who assigned a clinical classification using clinical features only. A neuroradiologist classified recent clinically relevant infarcts on brain imaging as cortical, posterior cerebral artery territory or lacunar. Of 1772 first ever strokes, there were 637 patients with PACS and 377 patients with LACS who had CT or MRI. Recent infarcts were seen in 395 PACS and 180 LACS. Atrial fibrillation was more common in PACS with cortical than lacunar infarcts (OR 2.3, 95% confidence interval (95% CI) 0.9-5.5), and in LACS with cortical than lacunar infarcts (OR 3.9, 1.2-12). Severe ipsilateral carotid stenosis or occlusion was more common in PACS with cortical than lacunar infarcts (OR 3.5, 1.3-9.5); and in LACS with cortical than lacunar infarcts (OR 3.7, 1.1-12). In conclusion, patients with cortical infarcts are more likely to have severe ipsilateral carotid stenosis or atrial fibrillation than those with lacunar infarcts irrespective of the presenting clinical syndrome. Brain imaging should modify the clinical classification and influence patient investigation.","Brain/blood supply;Carotid Stenosis/diagnosis/pathology;Cerebral Infarction/diagnosis/ pathology/therapy;Dementia, Multi-Infarct/diagnosis/ pathology/therapy;Humans;Patient Care Planning;Retrospective Studies;Risk Factors;Stroke/diagnosis/ pathology/therapy;Tomography, X-Ray Computed","Mead, G. E.;Lewis, S. C.;Wardlaw, J. M.;Dennis, M. S.;Warlow, C. P.",1999,Nov,,0,
2573,"White matter lucencies on computed tomography, subacute arteriosclerotic encephalopathy (Binswanger's disease), and blood pressure","Of 1,643 cranial computed tomography (CT) scans done in a primary-tertiary care private hospital over a 1-year period, 11 (0.67%) showed diffuse confluent white matter lucencies of less than 30 Hounsfield units. By retrospective analysis, at least 4 of the 11 were demented. Of these, 3 had clinical evidence of Binswanger's disease--characterized by progressive dementia, incontinence, variable pseudobulbar signs, and acute and subacute motor deficits. Two additional patients suffered only transient ischemic attacks or lacunar strokes; 2 had syncope; 1 had multiple sclerosis. The remaining patients were neurologically asymptomatic. In this small retrospective series, the severity of CT changes did not distinguish the patients with clinical Binswanger's syndrome from neurologically less symptomatic patients. Ten of the eleven patients had disordered blood pressure regulation--hypertension, labile systolic pressure, orthostatic hypotension, or a combination of these factors. The severity of CT changes correlated more clearly with blood pressure instability than with clinical encephalopathy. Asymptomatic adult patients with unexplained CT white matter hypodensity and blood pressure disorders may, however, be at risk for the development of subsequent subacute arteriosclerotic encephalopathy.","Aged;Aged, 80 and over;*Blood Pressure;Dementia/*radiography;Demyelinating Diseases/*radiography;Female;Humans;Hypertension/complications;Hypotension, Orthostatic/complications;Intracranial Arteriosclerosis/complications/*radiography;Male;Middle Aged;Retrospective Studies;Risk;Syndrome;Tomography, X-Ray Computed","McQuinn, B. A.;O'Leary, D. H.",1987,Sep-Oct,,0,
2574,Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing,"Background: hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer's disease pathology. Objective: to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects: two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years. Methods: BP was assessed biennially between 64 and 68 years and brain MRI performed at 68 years. The risk factors of interest were diastolic and systolic BP and their visit-to-visit variability. Outcomes were WMH abundance and hippocampal volume. Regression models, controlling for confounding factors, examined their relationships. Results: higher diastolic BP predicted increased WMH (beta = 0.13, P = 0.044) and smaller hippocampi (beta = -0.25, P = 0.006). In contrast, increased systolic BP predicted larger hippocampi (beta = 0.22, P = 0.013). Variability of diastolic BP predicted lower hippocampal volume (beta = -0.15, P = 0.033). These relationships were independent of confounding life-course risk factors. Anti-hypertensive medication did not modify these relationships, but was independently associated with increased WMH (beta = 0.17, P = 0.011). Conclusion: increased diastolic BP is associated with biomarkers of both cerebrovascular and Alzheimer's diseases, whereas the role of systolic BP is less clear, with evidence for a protective effect on hippocampal volume. These differing relationships emphasise the importance of considering individual BP components with regard to brain ageing and pathology. Interventions targeting diastolic hypertension and its chronic variability may provide new strategies able to slow the accumulation of these harmful pathologies.",diastolic;hippocampus;hyperintensities;systolic;variability,"McNeil, C. J.;Myint, P. K.;Sandu, A. L.;Potter, J. F.;Staff, R.;Whalley, L. J.;Murray, A. D.",2018,Jan 1,,0,
2575,Cholinergic subcortical hyperintensities in Alzheimer's disease patients from the Sunnybrook Dementia Study: relationships with cognitive dysfunction and hippocampal atrophy,"BACKGROUND: Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD). OBJECTIVE: To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy. METHODS: A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores. RESULTS: Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, rho = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume. CONCLUSION: These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/ psychology;Atrophy/pathology/psychology;Cholinergic Fibers/ pathology;Cognition/ physiology;Executive Function/physiology;Female;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Neuropsychological Tests","McNeely, A. A.;Ramirez, J.;Nestor, S. M.;Zhao, J.;Gao, F.;Kiss, A.;Stuss, D. T.;Black, S. E.",2015,,10.3233/jad-140588,0,
2576,Creutzfeldt-Jakob disease presenting acutely as stroke; an analysis of 30 cases,"Creutzfeldt-Jakob disease (CJD) presenting acutely with single or grouped symptoms simulating stroke has been described previously but no systematic review of these particular patients has been attempted. We undertook a retrospective review of the United Kingdom database comprising records from 1970 to 1994 of 532 patients with 'definite' or 'probable' CJD. Thirty cases (5.6%) were identified where the onset of symptoms was sufficiently abrupt to be diagnosed as a stroke by a consultant physician or neurologist or fulfilled standard criteria for stroke. Of 29 patients who had a CT scan, five (17%) were reported to have an infarct appropriate to the clinical signs, and a further five showed 'other' infarcts. Several patients were extensively investigated and treated for stroke, before the correct diagnosis became apparent. The median time from presentation to death was 12 weeks (range 4-38 weeks) which is not significantly different from that of the CJD patients as a whole.",adult;aged;article;brain infarction;clinical article;clinical feature;computer assisted tomography;Creutzfeldt Jakob disease;female;human;male;priority journal;retrospective study;cerebrovascular accident,"McNaughton, H. K.;Will, R. G.",1997,,,0,
2577,Cognitive performance after lacunar stroke correlates with leukoaraiosis severity,"BACKGROUND: This study investigates the effect of leukoaraiosis on patients presenting with cognitive impairment after lacunar stroke. METHODS: Fourty-six patients with cognitive impairment and newly discovered lacunar stroke detected by brain magnetic resonance imaging underwent neuropsychological testing. RESULTS: Patients with both lacunar infarct and leukoaraiosis performed less well on cognitive measures, compared to those with lacunar infarcts alone. Additionally, leukoaraiosis severity inversely correlated with cognitive performance. CONCLUSIONS: In patients with lacunar stroke, presence of leukoaraiosis is associated with worse performance in multiple cognitive domains. These findings suggest lacunar infarcts plus leukoaraiosis is a common etiology for vascular dementia.","Adult;Aged;Aged, 80 and over;Brain Infarction/ complications/pathology/psychology;Cognition;Cognition Disorders/ etiology/pathology/psychology;Female;Humans;Leukoaraiosis/complications/ etiology/pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Severity of Illness Index;Stroke/ complications/diagnosis/etiology/psychology","McMurtray, A. M.;Liao, A.;Haider, J.;Licht, E.;Mendez, M. F.",2007,,10.1159/000105679,0,
2578,Small-vessel vascular disease in human immunodeficiency virus infection: the Hawaii aging with HIV cohort study,"BACKGROUND: This study is designed to determine the relationship between age and occurrence of cerebral manifestations of small-vessel ischemic vascular disease in human immunodeficiency virus (HIV)-seropositive individuals. METHODS: Periventricular leukoaraiosis severity and white matter lesion volume were determined by magnetic resonance imaging of the brain of 57 HIV-seropositive individuals. RESULTS: Cerebral small-vessel ischemic vascular disease manifestations correlated with age and systolic blood pressure, but not with HIV infection-related parameters. CONCLUSIONS: These findings suggest that, in the era of highly active antiretroviral therapy, leukoaraiosis severity and white matter lesion volume may be more indicative of small-vessel ischemic vascular disease than HIV-related CNS pathology, and support the need for aggressive treatment of vascular risk factors in HIV-seropositive individuals.",AIDS Dementia Complex/etiology/pathology/virology;Adult;Age Factors;Aging/ pathology;Blood Pressure;Brain Ischemia/ complications/pathology/physiopathology;Cerebral Arteries/ pathology/physiopathology;Cohort Studies;Female;HIV Seropositivity/ complications/pathology/physiopathology;Hawaii;Humans;Leukoaraiosis/complications/ etiology/pathology/physiopathology;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Population Surveillance;Risk Assessment;Risk Factors;Severity of Illness Index,"McMurtray, A.;Nakamoto, B.;Shikuma, C.;Valcour, V.",2007,,10.1159/000104484,0,
2579,The value of HMPAO SPECT scanning in the diagnosis of early Alzheimer's disease in patients attending a memory clinic,"The value of hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomograpy (SPECT) as a diagnostic test for Alzheimer's disease (AD) was assessed in 44 patients attending a Memory Clinic. A comprehensive physical and psychiatric examination and detailed neuropsychological tests were used to arrive at a clinical diagnosis, in accordance with NINCDS-ADRDA criteria. The mean patient age was 69 (range 59-84) years, and the mean score on the Mini-Mental State Examination (MMSE) was 24 (range 7-30). Of 26 patients with a clinical diagnosis of AD, only 15 demonstrated a scan pattern strongly suggestive of AD. Four scans were normal, four showed evidence of ischaemic change and three were in the category 'other', one of which showed bilateral frontal hypoperfusion, but normal temporoparietal flow. Of the eight patients considered by clinical criteria to be non-demented, no scan showed an AD pattern, but three showed an ischaemic pattern. Both of the patients diagnosed clinically as suffering from multi-infarct dementia showed SPECT scan evidence of ischaemic change. Of the remaining eight patients with other clinical diagnoses only one scan suggested AD. We conclude that the HMPAO SPECT scan appearances which arise from AD in the early stages of the disease do not on their own allow the disease to be accurately diagnosed, but they may be useful if interpreted in conjunction with other imaging techniques.",,"McMurdo, M. E. T.;Grant, D. J.;Kennedy, N. S. J.;Gilchrist, J.;Findlay, D.;McLennan, J. M.",1994,1994,,0,
2580,Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration,"Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are sensitive for tau or TDP-43 pathology in frontotemporal lobar degeneration (FTLD). Neuroimaging analyses have revealed distinct distributions of disease in FTLD patients with genetic mutations. However, genetic influences on neuroanatomic structure in sporadic FTLD have not been assessed. In this report, we use novel multivariate tools, Eigenanatomy, and sparse canonical correlation analysis to identify associations between SNPs and neuroanatomic structure in sporadic FTLD. Magnetic resonance imaging analyses revealed that rs8070723 (MAPT) was associated with gray matter variance in the temporal cortex. Diffusion tensor imaging analyses revealed that rs1768208 (MOBP), rs646776 (near SORT1), and rs5848 (PGRN) were associated with white matter variance in the midbrain and superior longitudinal fasciculus. In an independent autopsy series, we observed that rs8070723 and rs1768208 conferred significant risk of tau pathology relative to TDP-43, and rs646776 conferred increased risk of TDP-43 pathology relative to tau. Identified brain regions and SNPs may help provide an in vivo screen for underlying pathology in FTLD and contribute to our understanding of sporadic FTLD.","Adaptor Proteins, Vesicular Transport/genetics;Brain/ pathology;DNA-Binding Proteins/ genetics;Diffusion Tensor Imaging;Female;Frontotemporal Lobar Degeneration/ genetics/ pathology;Genome-Wide Association Study;Humans;Male;Middle Aged;Mutation;Myelin Proteins/genetics;Neuroimaging;Polymorphism, Single Nucleotide/ genetics;Risk;tau Proteins/ genetics","McMillan, C. T.;Toledo, J. B.;Avants, B. B.;Cook, P. A.;Wood, E. M.;Suh, E.;Irwin, D. J.;Powers, J.;Olm, C.;Elman, L.;McCluskey, L.;Schellenberg, G. D.;Lee, V. M.;Trojanowski, J. Q.;Van Deerlin, V. M.;Grossman, M.",2014,Jun,10.1016/j.neurobiolaging.2013.11.029,0,
2581,White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration,"BACKGROUND: Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI). METHODS: Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-one-out cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort. RESULTS: ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLD-TAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP. CONCLUSIONS: These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLD-TAU, and emphasise the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.","Aged;Anisotropy;Autopsy;Brain/ pathology;Cohort Studies;Corpus Callosum/pathology;DNA-Binding Proteins/ metabolism;Diagnosis, Differential;Diffusion Tensor Imaging;Educational Status;Female;Frontotemporal Lobar Degeneration/diagnosis/ pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuroimaging;Neuropsychological Tests;ROC Curve;TDP-43 Proteinopathies/ metabolism/ pathology;tau Proteins/ metabolism","McMillan, C. T.;Irwin, D. J.;Avants, B. B.;Powers, J.;Cook, P. A.;Toledo, J. B.;McCarty Wood, E.;Van Deerlin, V. M.;Lee, V. M.;Trojanowski, J. Q.;Grossman, M.",2013,Sep,10.1136/jnnp-2012-304418,0,
2582,White matter imaging contributes to the multimodal diagnosis of frontotemporal lobar degeneration,"OBJECTIVE: To evaluate the distribution of white matter (WM) disease in frontotemporal lobar degeneration (FTLD) and Alzheimer disease (AD) and to evaluate the relative usefulness of WM and gray matter (GM) for distinguishing these conditions in vivo. METHODS: Patients were classified as having FTLD (n = 50) or AD (n = 42) using autopsy-validated CSF values of total-tau:beta-amyloid (t-tau:Abeta(1-42)) ratios. Patients underwent WM diffusion tensor imaging (DTI) and volumetric MRI of GM. We employed tract-specific analyses of WM fractional anisotropy (FA) and whole-brain GM density analyses. Individual patient classification was performed using receiver operator characteristic (ROC) curves with FA, GM, and a combination of the 2 modalities. RESULTS: Regional FA and GM were significantly reduced in FTLD and AD relative to healthy seniors. Direct comparisons revealed significantly reduced FA in the corpus callosum in FTLD relative to AD. GM analyses revealed reductions in anterior temporal cortex for FTLD relative to AD, and in posterior cingulate and precuneus for AD relative to FTLD. ROC curves revealed that a multimodal combination of WM and GM provide optimal classification (area under the curve = 0.938), with 87% sensitivity and 83% specificity. CONCLUSIONS: FTLD and AD have significant WM and GM defects. A combination of DTI and volumetric MRI modalities provides a quantitative method for distinguishing FTLD and AD in vivo.","Aged;Alzheimer Disease/ diagnosis;Anisotropy;Brain/ pathology;Cerebral Cortex/pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Frontotemporal Lobar Degeneration/ diagnosis;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests;ROC Curve;Sensitivity and Specificity","McMillan, C. T.;Brun, C.;Siddiqui, S.;Churgin, M.;Libon, D.;Yushkevich, P.;Zhang, H.;Boller, A.;Gee, J.;Grossman, M.",2012,May 29,10.1212/WNL.0b013e31825830bd,0,
2583,Multimodal imaging evidence of pathology-mediated disease distribution in corticobasal syndrome,"OBJECTIVE: To use multimodal neuroimaging to evaluate the influence of heterogeneous underlying pathology in corticobasal syndrome (CBS) on the neuroanatomical distribution of disease. METHODS: We performed a retrospective evaluation of 35 patients with CBS with T1-weighted MRI, diffusion tensor imaging, and neuropathologic, genetic, or CSF evidence of underlying pathology. Patients were assigned to 2 groups: those with evidence of Alzheimer pathology (CBS-AD) and those without Alzheimer pathology (CBS-non-AD). Group comparisons of CBS-AD and CBS-non-AD assessed clinical features, gray matter (GM) cortical thickness, and white matter (WM) fractional anisotropy. RESULTS: CBS-AD was found in 34% (n = 12) and CBS-non-AD in 66% (n = 23) of CBS patients. Clinical evaluations revealed that CBS-non-AD had a higher frequency of asymmetric rigidity compared to CBS-AD, but groups otherwise did not differ in dementia severity, impairments in cognition, or rates of extrapyramidal symptoms. We found frontoparietal GM and WM disease in each group compared to healthy, demographically comparable controls, as well as multimodal neuroimaging evidence of a double dissociation: CBS-non-AD had WM disease in the corpus callosum, corticospinal tract, and superior longitudinal fasciculus relative to CBS-AD, and CBS-AD had reduced temporoparietal GM relative to CBS-non-AD, including the precuneus and posterior cingulate. CONCLUSIONS: Patients with CBS have a pathology-mediated dissociation of GM and WM disease. Multimodality neuroimaging may be useful for improving in vivo pathologic diagnosis of CBS.",,"McMillan, C. T.;Boyd, C.;Gross, R. G.;Weinstein, J.;Firn, K.;Toledo, J. B.;Rascovsky, K.;Shaw, L.;Wolk, D. A.;Irwin, D. J.;Lee, E. B.;Trojanowski, J. Q.;Grossman, M.",2016,Sep 20,10.1212/wnl.0000000000003119,0,
2584,A Simplified Approach to Encephalitis and Its Mimics: Key Clinical Decision Points in the Setting of Specific Imaging Abnormalities,"Rationale and Objectives Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis. Materials and Methods Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts. Results Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences. Conclusions Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care.",acute disseminated encephalomyelitis;article;brain cortex;brain infarction;brain tumor;computer assisted tomography;Creutzfeldt Jakob disease;diagnostic imaging;Epstein Barr virus encephalitis;gray matter;herpes simplex encephalitis;herpes zoster encephalitis;human;Human immunodeficiency virus encephalitis;infectious encephalitis;lymphoma;medical record;metabolic disorder;nuclear magnetic resonance imaging;paraneoplastic neuropathy;posterior reversible encephalopathy syndrome;primary tumor;priority journal;rabies;rabies encephalitis;seizure;temporal lobe;virus encephalitis;West Nile virus encephalitis;white matter,"McKnight, C. D.;Kelly, A. M.;Petrou, M.;Nidecker, A. E.;Lorincz, M. T.;Altaee, D. K.;Gebarski, S. S.;Foerster, B.",2017,,10.1016/j.acra.2016.04.013,0,
2585,Vascular cognitive change: Perspective from neurology,"In summary, the interaction between vascular changes and Alzheimer's disease is a critical question that remains to be fully elucidated. On the basis of the evidence to date, it is logical to assume that any given individual with dementia might have some degree of vascular pathology and some degree of Alzheimer's disease pathology. Current diagnostic paradigms do not go far enough in terms of differentiating underlying pathologies; only brain imaging, MRI in particular, can reveal subsymptomatic cerebrovascular changes. Similarly, there are scant evidence-based data to guide clinicians in the treatment of vascular dementia or mixed dementia that might be primarily a result of, or worsened by, vascular pathology. The existing data do suggest that preventing further cerebrovascular disease, whether silent or symptomatic stroke or small vessel disease, is one clear strategy for intervening to potentially reduce the burden of cognitive impairment and dementia. © 2007 The Alzheimer's Association.",,"McKhann, G. M.;Selnes, O. A.",2007,April,,0,
2586,Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease,"Clinical criteria for the diagnosis of Alzheimer's disease include insidious onset and progressive impairment of memory and other cognitive functions. There are no motor, sensory, or coordination deficits early in the disease. The diagnosis cannot be determined by laboratory tests. These tests are important primarily in identifying other possible causes of dementia that must be excluded before the diagnosis of Alzheimer's disease may be made with confidence. Neuropsychological tests provide confirmatory evidence of the diagnosis of dementia and help to assess the course and response to therapy. The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information become available.","Alzheimer Disease/*diagnosis/diagnostic imaging/psychology;Humans;Psychological Tests;Tomography, Emission-Computed;Tomography, X-Ray Computed;United States;United States Dept. of Health and Human Services","McKhann, G.;Drachman, D.;Folstein, M.;Katzman, R.;Price, D.;Stadlan, E. M.",1984,Jul,,0,
2587,Executive functioning in Alzheimer's disease and vascular dementia,"OBJECTIVE: To compare performance of patients with mild-moderate Alzheimer's disease (AD) and vascular dementia (VaD) on tests of executive functioning and working memory. METHODS: Patients with AD (n = 76) and VaD (n = 46) were recruited from a memory clinic along with dementia free participants (n = 28). They underwent specific tests of working memory from the Cognitive Drug Research (CDR) battery and pen and paper tests of executive function including CLOX 1 & 2, EXIT25 and a test of verbal fluency (COWAT). All patients had a CT brain scan which was independently scored for white matter change/ischaemia. RESULTS: The AD and VaD groups were significantly impaired on all measures of working memory and executive functioning compared to the disease free group. There were no significant differences between the AD and VaD groups on any measure. Z-scores confirmed the pattern of impairment in executive functioning and working memory was largely equivalent in both patient groups. Small to moderate correlations were seen between the MMSE and the neurocognitive scores in both patient groups and the pattern of correlations was also very similar in both patient groups. CONCLUSIONS: This study demonstrates sizeable executive functioning and working memory impairments in patients with mild-moderate AD and VaD but no significant differences between the disease groups.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*psychology;Analysis of Variance;Dementia, Vascular/diagnosis/*psychology;*Executive Function;Female;Humans;Male;Neuropsychological Tests/statistics & numerical data;Reference Values;Severity of Illness Index;Task Performance and Analysis;Tomography, X-Ray Computed","McGuinness, B.;Barrett, S. L.;Craig, D.;Lawson, J.;Passmore, A. P.",2010,Jun,10.1002/gps.2375,0,
2588,Attention deficits in Alzheimer's disease and vascular dementia,"OBJECTIVE: To compare the performance of patients with mild-moderate Alzheimer's disease (AD) and vascular dementia (VaD) on tests of information processing and attention. METHOD: Patients with AD (n=75) and VaD (n=46) were recruited from a memory clinic along with dementia-free participants (n=28). They underwent specific tests of attention from the Cognitive Drug Research battery, and pen and paper tests including Colour Trails A and B and Stroop. All patients had a CT brain scan that was independently scored for white-matter change/ischaemia. RESULTS: Attention was impaired in both AD and VaD patients. VaD patients had more impaired choice reaction times and were less accurate on a vigilance test measuring sustained attention. Deficits in selective and divided attention occurred in both patient groups and showed the strongest correlations with Mini Mental State Examination scores. CONCLUSION: This study demonstrates problems with the attentional network in mild-moderate AD and VaD. The authors propose that attention should be tested routinely in a memory clinic setting.","Aged;Alzheimer Disease/*epidemiology;*Attention;Cerebrovascular Disorders/epidemiology;Cognition Disorders/diagnosis/*epidemiology;Dementia, Vascular/diagnosis/*epidemiology;Female;Humans;Male;Neuropsychological Tests;Prevalence;Severity of Illness Index","McGuinness, B.;Barrett, S. L.;Craig, D.;Lawson, J.;Passmore, A. P.",2010,Feb,10.1136/jnnp.2008.164483,0,
2589,Magnetic resonance findings in patients with early-onset Alzheimer's disease,"The magnetic resonance scans of 22 patients with early-onset Alzheimer's disease (AD) were compared to 16 age-matched neurologically normal controls for the presence of white matter subcortical hyperintensities (SCH) and periventricular hyperintensities (PVH). Patients with AD were significantly more likely to have evidence of PVH (p less than 0.01) than age-matched controls. There was no significant difference between the two groups in either the frequency of SCH or the size of the largest lesion. Within the AD group, there was no difference demonstrated in the location of the SCH, either in the anterior-posterior plane or between the two hemispheres. Patients with AD more frequently demonstrated ventriculomegaly (p less than 0.001) and sulcal widening (p less than 0.05) compared with controls. This study suggests that the SCH seen in early-onset AD patients on MRI are related more to the aging process than to the AD process and that the increased frequency of PVH may have a relationship to the disease process.",Aged;Alzheimer Disease/*diagnosis/psychology;Brain/*pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests,"McDonald, W. M.;Krishnan, K. R.;Doraiswamy, P. M.;Figiel, G. S.;Husain, M. M.;Boyko, O. B.;Heyman, A.",1991,Apr 15,,0,
2590,Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?,"Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein-related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD.",,"McDonald, C.;Newton, J. L.;Burn, D. J.",2016,,,0,
2591,White matter predicts functional connectivity in premanifest Huntington's disease,"Objectives: The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Methods: Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. Results: We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Interpretation: Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero–posterior dissociation that is in keeping with the caudo–rostral gradient of striatal pathology in HD.",adult;algorithm;antero posterior analysis;article;cohort analysis;controlled study;data processing;diffusion tensor imaging;disease assessment;female;functional connectivity;functional magnetic resonance imaging;graph theory metrics;human;Huntington chorea;major clinical study;male;mathematical parameters;nervous system parameters;nuclear magnetic resonance scanner;priority journal;radiological parameters;regions of interest;resting state network;structural hub region;white matter,"McColgan, P.;Gregory, S.;Razi, A.;Seunarine, K. K.;Gargouri, F.;Durr, A.;Roos, R. A. C.;Leavitt, B. R.;Scahill, R. I.;Clark, C. A.;Tabrizi, S. J.;Rees, G.;Coleman, A.;Decolongon, J.;Fan, M.;Petkau, T.;Jauffret, C.;Justo, D.;Lehericy, S.;Nigaud, K.;Valabrègue, R.;choonderbeek, A.;Hart, E. P. T.;Hensman Moss, D. J.;Crawford, H.;Johnson, E.;Papoutsi, M.;Berna, C.;Reilmann, R.;Weber, N.;Stout, J.;Labuschagne, I.;Landwehrmeyer, B.;Orth, M.;Johnson, H.",2017,,10.1002/acn3.384,0,
2592,Cerebral magnetic resonance imaging compared in Alzheimer's and multi-infarct dementia,"Cerebral magnetic resonance images (MRI) were compared between two groups, each of 25 patients, one with senile dementia of the Alzheimer's type (SDAT) and the other with multi-infarct dementia (MID). MRI proved to be clinically useful for differentiating SDAT from MID, utilizing a multivariate model of six MRI criteria as follows: ventricular-brain ratio, presence of subcortical infarcts, bifrontal ventricular ratio, bicaudate ventricular ratio, third ventricular ratio, and presence of diffuse periventricular high-intensity white matter lucencies. Utilizing all six MRI criteria, classification by discriminant function analysis provided 84% correct diagnostic agreement with clinical classification of MID patients, 92% for SDAT patients, and 88% for the total cohort of demented patients.",,"McClintic Reed, K.;Rogers, R. L.;Meyer, J. S.",1991,1991,,0,
2593,Diagnostic neuroimaging in stroke. The complementary roles of referring physician and neuroradiologist,"The number and sophistication of neuroimaging methods for identifying location, size, type, and causes of stroke or stroke-like syndromes have expanded rapidly. In acute stroke, computed tomography is used to distinguish between nonhemorrhagic and hemorrhagic infarction and to eliminate several potential alternative diagnoses. Cerebral angiography can identify surgically treatable lesions in patients experiencing transient ischemic attacks and thus aid in preventing stroke. The superb sensitivity of magnetic resonance imaging has opened new vistas in the ongoing investigation of multiinfarct dementia and small infarcts in neurologically ""noneloquent"" regions of the brain. The more complete the referring physician's clinical and neurologic workup, the more able is the neuroradiologist to structure and coordinate the safest, fastest, and most cost-effective plan of neuroimaging to diagnose a patient's neurologic problem.","Cerebral Angiography;Cerebrovascular Disorders/prevention & control/ radiography;Humans;Magnetic Resonance Spectroscopy;Radiographic Image Enhancement;Tomography, Emission-Computed;Tomography, X-Ray Computed","McCabe, M. J.",1986,Sep 15,,0,
2594,Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study,"Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.",AIDS-Related Complex/complications/pathology;Acquired Immunodeficiency Syndrome/complications/pathology;Adult;Alcohol Drinking;Brain/ pathology;Brain Diseases/complications/ pathology;Cohort Studies;HIV Infections/complications/ pathology;HIV-1/immunology;Humans;Hypertension/complications;Magnetic Resonance Imaging;Male;Multicenter Studies as Topic;Smoking;Substance-Related Disorders/complications,"McArthur, J. C.;Kumar, A. J.;Johnson, D. W.;Selnes, O. A.;Becker, J. T.;Herman, C.;Cohen, B. A.;Saah, A.",1990,,,0,
2595,"Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease","Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPtau) and amyloid-beta (Abeta) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups. We investigated differences in the composition and aetiology of parietal WML from AD and non-demented controls. Parietal WML tissue from 55 human post-mortem brains (AD, n = 27; non-demented controls, n = 28) were quantitatively assessed for axonal loss and demyelination, as well as for cortical HPtau and Abeta burden and SVD. Biochemical assessment included Wallerian degeneration protease calpain and the myelin-associated glycoprotein (MAG) to proteolipid protein (PLP) ratio (MAG:PLP) as a measure of hypoperfusion. WML severity was associated with both axonal loss and demyelination in AD, but only with demyelination in controls. Calpain was significantly increased in WML tissue in AD, whereas MAG:PLP was significantly reduced in controls. Calpain levels were associated with increasing amounts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition and aetiology compared to WML seen in aged controls: WML seen in AD may be associated with Wallerian degeneration that is triggered by cortical AD-pathology, whereas WML in aged controls are due to ischaemia. Hence, parietal WML as seen on MRI should not invariably be interpreted as a surrogate biomarker for SVD as they may be indicative of cortical AD-pathology, and therefore, AD should also be considered as the main underlying cause for cognitive impairment in cases with parietal WML.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology;Cerebral Small Vessel Diseases/complications/ pathology;Female;Humans;Male;Nerve Degeneration/complications/ pathology;Parietal Lobe/ pathology;White Matter/ pathology;Alzheimer's disease;Hyperphosphorylated tau;Small vessel disease;Wallerian degeneration;White matter hyperintensity;White matter lesion","McAleese, K. E.;Walker, L.;Graham, S.;Moya, E. L. J.;Johnson, M.;Erskine, D.;Colloby, S. J.;Dey, M.;Martin-Ruiz, C.;Taylor, J. P.;Thomas, A. J.;McKeith, I. G.;De Carli, C.;Attems, J.",2017,Sep,,0,
2596,"Magnetic resonance imaging of fixed post mortem brains reliably reflects subcortical vascular pathology of frontal, parietal and occipital white matter","AIMS: Subcortical vascular pathology of the white and deep grey matter (WM and DGM) is associated with cognitive impairment. Routine neuropathological assessment of subcortical vascular pathology is based on semiquantitative scoring of characteristic lesions in a limited number of histological slides from selected WM and DGM areas. Clinically, WM and DGM lesions are visualized as hyper-intensities on magnetic resonance imaging (MRI). The aim of this study was to evaluate the feasibility of MRI on fixed post mortem brain hemispheres to complement routine neuropathological assessment of subcortical vascular pathology. METHODS: We assessed subcortical vascular pathology in 40 post mortem brain hemispheres from demented (n = 26) and nondemented (n = 14) individuals (mean age 83.2 +/- 14.8 years; 62.5% female) using (i) routine histological assessment; (ii) extensive histological assessment of the entire hemisphere at 7-mm intervals; and (iii) full T2-weighted MRI performed on fixed post mortem brain hemispheres. RESULTS: In both WM and DGM routine histological scores for subcortical vascular pathology were significantly lower (P < 0.01) than the corresponding scores obtained by extensive histological assessment. In contrast, no significant differences were seen between scores obtained by MRI and extensive histological assessment in frontal, parietal and occipital lobes while MRI scores were significantly lower in the temporal WM and DGM (P < 0.01). CONCLUSIONS: The results of our study indicate that routine histological assessment underrates subcortical vascular pathology and we conclude that MRI could be used in addition to complement neuropathological post mortem assessment of subcortical vascular pathology of the WM.","Aged;Aged, 80 and over;Dementia/ pathology;Female;Frontal Lobe/blood supply/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Occipital Lobe/blood supply/ pathology;Parietal Lobe/blood supply/ pathology","McAleese, K. E.;Firbank, M.;Hunter, D.;Sun, L.;Hall, R.;Neal, J. W.;Mann, D. M.;Esiri, M.;Jellinger, K. A.;O'Brien, J. T.;Attems, J.",2013,Aug,10.1111/j.1365-2990.2012.01310.x,0,
2597,Cortical tau load is associated with white matter hyperintensities,"INTRODUCTION: Cerebral white matter lesions (WML), visualized as white matter hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss of integrity of the cerebral white matter (WM) and are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM damage may also be the result of degenerative axonal loss that is secondary to cortical Alzheimer's disease (AD) pathologies i.e., hyperphosphorylated tau (HPtau) and amyloid-beta (Abeta). Here we investigate the influence of HPtau, Abeta and SVD on WMH severity. RESULTS: 36 human post-mortem right fixed cerebral hemispheres (mean age 84.4 +/- 7.7 years; male: 16, female: 20) containing varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI with WMH assessed according to the age related white matter change scale (ARWMC). After dissection, using tissue samples from the frontal, temporal, parietal and occipital regions from the right hemisphere, we quantitatively assessed cortical HPtau and Abeta pathology burden by measuring the percentage area covered by AT8 immunoreactivity (HPtau-IR) and 4G8 immunoreactivity (Abeta-IR), and assessed the severity of WM SVD by calculating the sclerotic index (SI) of WM arteries/arterioles. HPtau-IR, Abeta-IR, and SI were compared with ARWMC scores. HPtau-IR, Abeta-IR and WM ARWMC scores were all significantly higher in AD cases compared to controls, while SI values were similar between groups. ARWMC scores correlated with HPtau-IR, Abeta-IR and SI in various regions, however, linear regression revealed that only HPtau-IR was a significant independent predictor of ARWMC scores. CONCLUSIONS: Here we have shown that increasing cortical HPtau burden independently predicted the severity of WMH indicating its potentially important role in the pathogenesis of WM damage. Moreover, our findings suggest that in AD patients the presence of WMH may indicate cortical AD-associated pathology rather than SVD. Further studies are warranted to elucidate the pathological processes that lead to WM damage and to clarify if WMH may serve as a general biomarker for cortical AD-associated pathology.",,"McAleese, K. E.;Firbank, M.;Dey, M.;Colloby, S. J.;Walker, L.;Johnson, M.;Beverley, J. R.;Taylor, J. P.;Thomas, A. J.;O'Brien, J. T.;Attems, J.",2015,,10.1186/s40478-015-0240-0,0,
2598,A novel Notch3 gene mutation not involving a cysteine residue in an Italian family with CADASIL,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to accumulating neurologic deficits and dementia. CADASIL has been linked to nucleotide substitutions and deletions in the Notch3 gene. All the mutations described until now lead to unpaired cysteine residue in the epidermal growth factor-like repeats. The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue.,"Adult;Aged;CADASIL/*genetics/pathology;Chromatography, High Pressure Liquid;Cysteine/chemistry;Exons/genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Pedigree;Protein Folding;Protein Structure, Tertiary;Proto-Oncogene Proteins/chemistry/*genetics;Receptors, Cell Surface/chemistry/*genetics;Receptors, Notch;Repetitive Sequences, Amino Acid;*Sequence Deletion;Structure-Activity Relationship","Mazzei, R.;Conforti, F. L.;Lanza, P. L.;Sprovieri, T.;Lupo, M. R.;Gallo, O.;Patitucci, A.;Magariello, A.;Caracciolo, M.;Gabriele, A. L.;Fera, F.;Valentino, P.;Bono, F.;Cenacchi, G.;Santoro, G.;Muglia, M.;Quattrone, A.",2004,Aug 10,,0,
2599,Longitudinal changes in microstructural white matter metrics in Alzheimer's disease,"BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. METHODS: Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. RESULTS: 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. CONCLUSION: The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.","AD, Alzheimer's disease;ADNI, Alzheimer's Disease Neuroimaging Initiative;Aging;Alzheimer's disease;DTI, diffusion tensor imaging;Diffusion tensor imaging;FA, fractional anisotropy;FSL, Functional MRI of the Brain Software Library;HC, healthy controls;MCI, mild cognitive impairment;MD, mean diffusivity;MMSE, Mini Mental Status Exam;MRI, magnetic resonance imaging;Magnetic resonance imaging;ROI, region of interest;TBSS, Tract-Based Spatial Statistics;WMS, Wechsler Memory Scale;White matter","Mayo, C. D.;Mazerolle, E. L.;Ritchie, L.;Fisk, J. D.;Gawryluk, J. R.;Alzheimer's Disease Neuroimaging, Initiative",2017,,,0,
2600,Cerebral autosomal dominant arteriopathy (CADASIL). Description of a German family,"We describe two members of a German family with cerebral autosomal dominant arteriopathy (CADASIL), which is characterized by recurrent subcortical ischemic strokes, mild dementia and leukoencephalopathy. The clinical features of the disease are suggestive of Binswanger's subcortical arteriosclerotic encephalopathy. However, it differs by the lack of hypertension and familial aggregation with autosomal dominant inheritance. Magnetic resonance imaging (MRI) of the brain shows subcortical ischemic infarcts affecting the periventricular white matter, the basal ganglia and the brain stem. On T2-weighted imaging, areas of hyperintensity were found in the white matter of both cerebral hemispheres with preponderance of frontal and anterotemporal regions. We assume that the underlying disease in this family is CADASIL with subcortical infarcts and leukoencephalopathy. The recently assigned disease locus on chromosome 19 was confirmed in this family. A treatment trial with acetylsalicylate was started in the affected members of the family.",,"Mayer, M.;Dichgans, M.;Gasser, T.;Buttner, U.;Uttner, I.;Straube, A.",1995,1995,,0,
2601,Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-beta,"Non-invasive imaging of amyloid-beta in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer (123)I-ABC577 as a potential imaging biomarker for amyloid-beta in the brain. The radio-iodinated imidazopyridine derivative (123)I-ABC577 was designed as a candidate for a novel amyloid-beta imaging agent. The binding affinity of (123)I-ABC577 for amyloid-beta was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer's disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of (123)I-ABC577. Furthermore, to validate (123)I-ABC577 as a biomarker for Alzheimer's disease, we performed a clinical study to compare the brain uptake of (123)I-ABC577 in three patients with Alzheimer's disease and three healthy control subjects. (123)I-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, (123)I-ABC577 showed high binding affinity for amyloid-beta and desirable pharmacokinetics in the preclinical studies. In the clinical study, (123)I-ABC577 was an effective marker for discriminating patients with Alzheimer's disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer's disease, (123)I-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by approximately 60% in patients with Alzheimer's disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer's disease showed minimal (123)I-ABC577 retention in the white matter. These observations indicate that (123)I-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-beta in the human brain. The availability of an amyloid-beta tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer's disease.",,"Maya, Y.;Okumura, Y.;Kobayashi, R.;Onishi, T.;Shoyama, Y.;Barret, O.;Alagille, D.;Jennings, D.;Marek, K.;Seibyl, J.;Tamagnan, G.;Tanaka, A.;Shirakami, Y.",2016,Jan,10.1093/brain/awv305,0,
2602,Carotid atherosclerotic markers in CADASIL,"PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL. METHODS: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded. RESULTS: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01). CONCLUSION: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results.","Adult;Aged;Biomarkers/blood;Brain/pathology;CADASIL/complications/*diagnosis/pathology/psychology;Carotid Artery Diseases/complications/*diagnosis/psychology/ultrasonography;Carotid Artery, Common/ultrasonography;Cognition;Cognition Disorders/etiology/psychology;Diffusion Magnetic Resonance Imaging;Disability Evaluation;Female;Humans;Linear Models;Male;Middle Aged;Neuropsychological Tests;Odds Ratio;Paris;Phenotype;Predictive Value of Tests;Prognosis;Prospective Studies;Risk Assessment;Risk Factors;Severity of Illness Index;Ultrasonography, Doppler, Duplex;Young Adult","Mawet, J.;Vahedi, K.;Aout, M.;Vicaut, E.;Duering, M.;Touboul, P. J.;Dichgans, M.;Chabriat, H.",2011,,10.1159/000321932,0,
2603,Sporadic diffuse leucoencephalopathy with axonal spheroids: Report of a profuse and rapid cortical-spinal degeneration,"Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement. © 2011 Springer-Verlag.",,"Maues De Paula, A.;Michel, B.;Dickson, D. W.;Wszolek, Z. K.;Pellissier, J. F.",2012,August,,0,
2604,"Migraine, white matter lesions and subarachnoid hemorrhage: Analysis of a large pedigree","Patients with migraine are at increased risk for white matter hyperintensities detected on magnetic resonance imaging (MRI). A 46-year-old woman had a history of migraine with and without aura for 20 years. Bilateral prominent hyperintense lesions were seen in centrum semiovale, posterior corona radia-ta, frontal white matter and periventricular regions on her T2- and FLAIR-weighted cranial MRIs. Thirteen members of her family, including her son, had a history of migraine and similar brain MRI lesions. Furthermore, three family members had a history of subarachnoid hemorrhage (SAH) and one member had intracranial aneurysm. Our current knowledge on associations, investigation plan and treatment of patients with migraine with white matter lesions of unknown significance is limited. Herein, for the first time, we report the association of this condition with familial SAH in a large pedigree. © Archives of Neuropsychiatry.",,"Matur, Z.;Poyraz, M.;Uyguner, O.;Kayserili, H.;Güveli, B.;Baykan, B.",2010,2010,,0,
2605,Cardiac myxomas: A long term study,"From 1980 to 1992 we followed 12 patients with cardiac myxomas for an average of 4.4 years (8 months-11 years). Presenting symptoms were neurological in four patients (hemiparesis, aphasia, visual field deficits, progressive dementia or vertigo), progressive dyspnoea in six, pulmonary embolism in one, and peripheral arterial or renal emboli in three. The diagnosis was suspected clinically in 11 patients. It was confirmed by echocardiography in ten and by thoracic CT in one. All these patients had cardiac surgery. One diagnosis was made at autopsy; the patient died unexpectedly during surgery for emboli to the leg arteries. At follow-up, two additional patients had died, one from myocardial infarction and one from rhabdomyosarcoma. Only one of the nine surviving patients had recurrent symptoms after cardiac surgery. His dementia continued to progress. The patients without new symptoms after cardiac surgery had normal MRI of the brain or residual ischaemic lesions. MRI of the patient with progressive dementia showed multiple cerebral lesions with a bright centre and a dark rim on T1- and T2-weighted spin-echo images. On CT there were many calcified lesions. CT, MR angiography and contrast angiography revealed multiple fusiform aneurysms. The rare occurrence of progressive neurological symptoms after myxoma resection with multiple cerebral lesions and aneurysms should suggest myxoma metastases to the brain.",,"Mattle, H. P.;Maurer, D.;Sturzenegger, M.;Ozdoba, C.;Baumgartner, R. W.;Schroth, G.",1995,1995,,0,
2606,Frequency and patterns of subclinical cognitive impairment in patients with ANCA-associated small vessel vasculitides,"We investigated the prevalence of disease-related cognitive impairment in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated small vessel vasculitides (SVV).We studied 43 patients with ANCA-associated SVV (Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MP)), with no evidence of focal neurological deficits and dementia and in whom other potential causes of cognitive decline were carefully excluded. All patients underwent a detailed neuropsychological evaluation and their performances were compared with those of matched healthy controls. Patients were considered to be affected by subclinical cognitive impairment when they had abnormal results in at least two neuropsychological tests. Magnetic resonance imaging (MRI) scans of the brain were also obtained in 11 patients.The average neuropsychological test scores were not significantly different between the SVV patients and the control subjects. Thirteen patients had abnormal results in two tests (seven patients) or three or more tests (six patients). Most frequently, abnormal tests were the Rey Figure Recall (six cases), the Wisconsin Card Sorting Test (six cases), and the reaction times (eight cases). The frequency and extent of brain MRI abnormalities were higher in impaired than in unimpaired patients.This study demonstrates that 30% of clinically nondemented SVV patients can have a subclinical neuropsychological impairment, characterized by mild abstract reasoning loss, mental speed reduction and nonverbal memory impairment. MRI findings in impaired patients are consistent with the presence of an SVV-mediated subcortical damage of the brain. Copyright © 2002 Elsevier Science B.V.",,"Mattioli, F.;Capra, R.;Rovaris, M.;Chiari, S.;Codella, M.;Miozzo, A.;Gregorini, G.;Filippi, M.",2002,30,,0,
2607,Combination benefit of cognitive rehabilitation plus donepezil for Alzheimer's disease patients,"OBJECTS: Alzheimer's disease (AD) is one of the most important diseases in aging society, and non-drug therapy might be an alternative therapeutic approach. Thus, we evaluated the add-on effect of cognitive rehabilitation on AD patients under donepezil treatment. METHODS: We retrospectively analyzed 55 AD patients with a Mini-Mental State Examination score of 15-25, dividing them into two groups depending on whether they were receiving ambulatory cognitive rehabilitation (group D + R, n = 32) or not (group D, n = 23) in Kurashiki Heisei Hospital over 1 year. The present cognitive rehabilitation included physical therapy, occupational therapy and speech therapy for 1-2 h once or twice a week. RESULTS: Between group D and group D + R, there was no significant difference in baseline data, such as age, Mini-Mental State Examination score, periventricular hyperintensity on magnetic resonance imaging, deep white matter hyperintensity on magnetic resonance imaging or donepezil dose (4.1 mg/day). At 1 year later, however, the Mini-Mental State Examination score improved only in group D + R from 21.7 to 24.0 (**P < 0.001), whereas that of group D remained at 21.5 with both groups of donepezil 5.0 mg/day. CONCLUSION: The combination of cognitive rehabilitation plus a choline esterase inhibitor donepezil showed a better effect for the cognitive function of AD patients than drug only therapy at 1 year. Geriatr Gerontol Int 2016; 16: 200-204.",,"Matsuzono, K.;Hishikawa, N.;Takao, Y.;Wakutani, Y.;Yamashita, T.;Deguchi, K.;Abe, K.",2016,Feb,10.1111/ggi.12455,0,
2608,Severe atrophy of amygdala and hippocampus in both Alzheimer's disease and multi-infarct dementia,"Alzheimer's disease and multi-infarct dementia are the two main diseases entirely different from each other producing almost the same abnormalities as dementia syndrome. With magnetic resonance imaging, severe atrophy of amygdala and hippocampus in both Alzheimer's disease and multi-infarct dementia was observed. There was no essential difference on the atrophic findings between Alzheimer's disease and multi-infarct dementia. This result therefore suggest that the quantitative measurement of amygdaloid and hippocampal atrophy predicts dementia.",,"Matsuzawa, T.;Hishinuma, T.;Matsui, H.;Meguro, K.;Ueda, M.;Kinomura, S.;Yamada, K.",1990,Dec,,0,
2609,"Limbic system, the main focus of dementia syndrome--a study with MRI and PET","Alzheimer disease and multi-infarct dementia are two entirely different diseases producing almost the same abnormalities as dementia syndrome. The statistical studies with MRI to locate the focus of dementia syndrome in the neocortex was an absolute failure. With MRI there is drastic atrophy and destruction of the amygdala and hippocampus suggesting the limbic system as the focus of dementia syndrome. Destruction of the limbic system in particular amygdala and hippampus produced the functional obstruction brought about by the marked reduction in the glucose utilization with PET in the bilateral temporal, parietal and occipital association cortices. Although this type constitutes only about 1/5 of all dementia patients. It is considered the fundamental type of dementia syndrome. Aside from this, there is a type wherein simultaneous and symmetrical reductions in glucose uterization of the frontal association cortex and the motor association cortex in the anterior part of the neocortex. This is referred to as type II. It constitutes about 4/5 of all dementia patients which is far more than type I. Based on these results, it is thought that limbic system is the main forcus of dementia syndrome.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/radionuclide imaging;Cerebral Infarction/*pathology/radionuclide imaging;Dementia/etiology/*pathology/radionuclide imaging;Humans;Limbic System/*pathology/radionuclide imaging;Magnetic Resonance Imaging;Middle Aged;Tomography, Emission-Computed","Matsuzawa, T.",1990,Dec,,0,
2610,Background and distribution of lobar microbleeds in cognitive dysfunction,"Objectives: Cerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D-CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL-CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M-CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL-CMBs and M-CMBs in terms of clinical features and regional distribution. Materials: We examined 176 sequential patients in our memory clinic for clinical features and CMB location using susceptibility-weighted images obtained on a 3T-MRI. The number of lobar CMBs in SL-CMBs and M-CMBs was counted in each cerebral lobe and their regional density was adjusted according to the volume of each lobe. Results: Of the total 176 patients, 111 patients (63.1%) had CMBs. Within the patients who had CMBs, M-CMBs were found in 54 patients (48.6%), followed by SL-CMBs in 35 (31.5%) and D-CMBs in 19 (17.1%). The SL-CMB group showed a significantly higher prevalence of family history of dementia, whereas the M-CMB group showed an increasing trend toward hypertension and smoking. The prevalence of AD was significantly higher in the SL-CMBs group, whereas the prevalence of AD with cerebrovascular disease was higher in the M-CMBs group. The regional density of lobar CMBs was significantly higher in the occipital lobe in the M-CMB group, whereas the SL-CMB group showed higher regional density between regions an increasing tendency in the parietal and occipital lobe. Conclusion: The between-group differences in clinical features and regional distribution indicate there to be an etiological relationship of SL-CMBs to AD and CAA, and M-CMBs to both HV and CAA.",cerebral amyloid angiopathy;cerebral microbleeds;hypertensive vasculopathy;magnetic resonance imaging;memory clinic,"Matsuyama, H.;Ii, Y.;Maeda, M.;Umino, M.;Ueda, Y.;Tabei, K. I.;Kida, H.;Satoh, M.;Shindo, A.;Taniguchi, A.;Takahashi, R.;Tomimoto, H.",2017,Nov,,0,
2611,Cerebral cortical and white matter lesions in amyotrophic lateral sclerosis with dementia: correlation with MR and pathologic examinations,"BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis with dementia (ALSD) is a progressive neurodegenerative disorder, characterized clinically by motor neuron symptoms and dementia, and pathologically by degeneration of the motor neurons of the brain and spinal cord as well as atrophy of the frontal and/or temporal lobes. So far, there has been no study on the correlation of MR images with histologic findings in ALSD. We studied the correlation of antemortem and postmortem T2-weighted MR images with histologic findings in autopsy-proved cases of ALSD. MATERIALS AND METHODS: Antemortem and postmortem T2-weighted images were compared with histologic findings in 3 autopsy-proved cases of ALSD. RESULTS: Antemortem MR images showed atrophy of the frontal and temporal lobes, which were asymmetric in the medial-ventral part of the temporal lobe. Faint linear T2-hyperintensity was seen in the medial-ventral part of the temporal subcortical white matter in 1 case. Postmortem T2-weighted images showed linear subcortical hyperintensity in the ventral-medial temporal lobe in each case. Histologically, cortical atrophy on MR images showed spongiform change with neuronal loss and gliosis especially in the superficial layers and linear subcortical hyperintensity on T2-weighted images showed degeneration and gliosis in each case. These findings are characteristic histologic changes of ALSD. CONCLUSION: MR imaging of atrophy of the frontal and temporal lobes with linear subcortical hyperintensities in the anteromedial temporal lobe is useful for diagnosis of ALSD.",Aged;Amyotrophic Lateral Sclerosis/ diagnosis;Atrophy;Brain/ pathology;Cadaver;Cerebral Cortex/ pathology;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies;Temporal Lobe/pathology,"Matsusue, E.;Sugihara, S.;Fujii, S.;Kinoshita, T.;Nakano, T.;Ohama, E.;Ogawa, T.",2007,Sep,10.3174/ajnr.A0605,0,
2612,White matter lesions in panencephalopathic type of Creutzfeldt-Jakob disease: MR imaging and pathologic correlations,"BACKGROUND AND PURPOSE: A panencephalopathic type of Creutzfeldt-Jakob disease (pCJD) is characterized by the extensive involvement of the cerebral white matter as well as the cerebral gray matter. It has been a point of controversy, however, whether the white matter changes represent primary or secondary degeneration. The aim of this study was to elucidate, by using MR images and histologic examinations, whether the white matter lesions in pCJD are primary or secondary degeneration. METHODS: Serial changes of T2 hyperintensities and histologic findings of six autopsy-proved cases of pCJD were retrospectively analyzed. RESULTS: Serial MR images of brains affected by pCJD revealed that T2 hyperintensities appeared in the cerebral gray matter 2-5 months after onset and in the cerebral white matter around the lateral ventricles approximately 5 months after onset. They rapidly extended to deep and subcortical white matter during the next several months and then to the entire cerebral white matter 10 months after onset. Histologic examination of the white matter lesions revealed spongy changes or tissue rarefaction associated with gemistocytic astrocytosis, which indicates primary involvement of the white matter. At the terminal stages of cases with a longer clinical course, MR images showed T2 hyperintensities in the corticospinal tracts in the internal capsule and brain stem, which histologically disclosed loss of myelin and axons accompanied by fibrillary gliosis that indicates secondary degeneration. CONCLUSION: Cerebral white matter lesions in pCJD were considered to be primary changes of the disease, but the lesions of the corticospinal tracts were secondary to cortical or cerebral or both white matter lesions.","Aged;Aged, 80 and over;Autopsy;Brain/pathology;Creutzfeldt-Jakob Syndrome/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies","Matsusue, E.;Kinoshita, T.;Sugihara, S.;Fujii, S.;Ogawa, T.;Ohama, E.",2004,Jun-Jul,,0,
2613,Genotype-phenotype correlations of cysteine replacement in CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images showed hyperintensities (HIs) in the deep white matter and the external capsule. We then investigated the mutations in NOTCH3 using direct sequencing within the region of intron-exon boundaries in exons 2-24 of NOTCH3. Eight patients harboring NOTCH3 mutations (8 of 10) were identified, including a novel mutation, p.C162Y, and 3 cases with a sporadic form. Seven patients with cysteine replacement showed HI in the anterior part of the temporal lobes (ATLs), whereas these changes were not detected in 1 patient without cysteine replacement, p.R75P. Reviewing previous reports, we conclude that the patients can clearly be divided in 2 groups: those with cysteine replacement who showed HI in the ATL and those without cysteine replacement who showed no HI in the ATL. Our findings expand the understanding of genotype-phenotype correlations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.","0 (NOTCH3 protein, human);0 (Receptor, Notch3);K848JZ4886 (Cysteine);Adult;Aged;CADASIL/diagnostic imaging/ genetics;Cysteine/ genetics;Exons/genetics;External Capsule/diagnostic imaging;Female;Genes, Dominant;Genetic Association Studies;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Neuroimaging;Phenotype;Receptor, Notch3/genetics;White Matter/diagnostic imaging;Cadasil;Genetics;Hereditary leukoaraiosis;Notch3","Matsushima, T.;Conedera, S.;Tanaka, R.;Li, Y.;Yoshino, H.;Funayama, M.;Ikeda, A.;Hosaka, Y.;Okuzumi, A.;Shimada, Y.;Yamashiro, K.;Motoi, Y.;Nishioka, K.;Hattori, N.",2017,Feb,,0,2614
2614,Genotype–phenotype correlations of cysteine replacement in CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images showed hyperintensities (HIs) in the deep white matter and the external capsule. We then investigated the mutations in NOTCH3 using direct sequencing within the region of intron-exon boundaries in exons 2–24 of NOTCH3. Eight patients harboring NOTCH3 mutations (8 of 10) were identified, including a novel mutation, p.C162Y, and 3 cases with a sporadic form. Seven patients with cysteine replacement showed HI in the anterior part of the temporal lobes (ATLs), whereas these changes were not detected in 1 patient without cysteine replacement, p.R75P. Reviewing previous reports, we conclude that the patients can clearly be divided in 2 groups: those with cysteine replacement who showed HI in the ATL and those without cysteine replacement who showed no HI in the ATL. Our findings expand the understanding of genotype–phenotype correlations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.",cysteine;Notch3 receptor;adult;aged;amino acid substitution;article;brain radiography;CADASIL;clinical article;clinical feature;exon;external capsule;female;gene frequency;genetic variability;genotype phenotype correlation;human;intron;male;middle aged;missense mutation;mutational analysis;NOTCH3 gene;nuclear magnetic resonance imaging;priority journal;sequence analysis;single nucleotide polymorphism;temporal lobe,"Matsushima, T.;Conedera, S.;Tanaka, R.;Li, Y.;Yoshino, H.;Funayama, M.;Ikeda, A.;Hosaka, Y.;Okuzumi, A.;Shimada, Y.;Yamashiro, K.;Motoi, Y.;Nishioka, K.;Hattori, N.",2017,,10.1016/j.neurobiolaging.2016.10.026,0,
2615,Differences in erythrocyte aggregability between multi-infarct dementia and Alzheimer's disease,"We reported previously that erythrocyte aggregability (RBC-A) is enhanced in patients with cerebral infarction. The purpose of the present study was to examine whether or not differences in RBC-A exist between multi-infarct dementia (MID) and Alzheimer's disease. The subjects comprised 16 patients with MID (7 males and 9 females, 73 +/- 11 years old) who had Hachinski's ischemic scores of 7 or more and displayed multiple infarctions on brain computed tomography and 18 patients with Alzheimer's disease (8 males and 10 females, 70 +/- 8 years old) who were diagnosed using the criteria proposed by the NINCDS-ADRDA Work Group. The patients underwent tests for cognitive function employing Hasegawa's dementia scale. RBC-A was measured using the whole-blood RBC aggregometer developed by us with concomitant measurement of blood factors such as the hematocrit, albumin/globulin ratio (A/G ratio) and fibrinogen. The RBC-A value in MID (0.170 +/- 0.030/s) was significantly higher (p < 0.01) than that in Alzheimer's disease (0.135 +/- 0.022/s). The hematocrit and concentration of fibrinogen did not reveal any differences between MID and Alzheimer's disease. However, the A/G ratio in MID (1.59 +/- 0.43) was significantly lower (p < 0.01) than in Alzheimer's disease (2.01 +/- 0.35). The above results suggest a potential usefulness for erythrocyte aggregability in differentiating between the two types of dementia.",,"Matsuoka, S.;Fukuuchi, Y.;Tomita, M.;Tanahashi, N.;Takeda, H.",1993,,10.1016/s1052-3057(10)80234-4,0,
2616,Cerebral white matter damage in frontotemporal dementia assessed by diffusion tensor tractography,"Introduction: We used diffusion tensor imaging (DTI) to study white matter integrity in patients with frontotemporal dementia (FTD). Methods: The subjects comprised 20 patients (9 men, 11 women) with FTD and 17 age-matched healthy controls (9 men, 8 women). Based on the data obtained from DTI, we performed tractography of the major cerebral pathways, including the pyramidal tracts, genu and splenium of the corpus callosum (CC), bilateral arcuate fasciculi (AF), inferior longitudinal fasciculi (ILF) and uncinate fasciculi (UF). We measured the values of fractional anisotropy (FA) in each fiber and statistically compared the findings in patients with those in controls. Results: We found a significant decrease in FA values in the selected association fibers as well as anterior fibers of the CC in the patients with FTD. The greatest decrease in mean FA of the UF was seen in advanced FTD. On the other hand, there were no significant differences in FA in the bilateral pyramidal tracts. Conclusion: The features of FTD from the view point of cerebral white matter damage were revealed by tractography based on DTI. DTI is therefore considered to be a useful method, and may provide clues to elucidating the pathogenesis of FTD. © 2008 Springer-Verlag.",,"Matsuo, K.;Mizuno, T.;Yamada, K.;Akazawa, K.;Kasai, T.;Kondo, M.;Mori, S.;Nishimura, T.;Nakagawa, M.",2008,July,,0,
2617,Assessments of executive function in patients with subcortical cerebral infarction using the behavioural assessment of the dysexecutive syndrome,"To assess executive functions in patients with subcortical cerebral infarctions, we performed neuropsychological tests including the Behavioural Assessment of the Dysexecutive Syndrome (BADS). BADS is an executive function test constructing of 6 subtests. We recruited 24 patients who had subcortical ischemia on magnetic resonance image (MRI). The BADS Japanese version, Trail Making Test (TMT) and Wisconsin Card Sorting Test (WCST) were employed. TMT and WCST are recognized executive function tests. We classified the participants into two categories in relation to the degree of deep white matter hyperintensity (DWMH) according to the classification of Fazekas. The low grade DWMH group consisted of 11 patients with punctate foci on MRI. The 13 patients showing the beginning of confluence of foci on MRI were categorized as the high grade DWMH group. All patients were right handed, and had no right hand disability impeding the test. We excluded patients with severe stenotic or occlusive lesions in cerebral arteries on brain magnetic resonance angiography. The Mini-mental State Examination (MMSE) was employed to exclude demented participants. To assess the mood of participant, we introduced the Japan Stroke Scale of Depression Scale (JSS-D). Statistical analysis was performed by Student's t-test. There was no significant difference in length of education, TMT, MMSE and JSS-D scores. The high grade DWMH group was significantly older. The WCST score were significantly impaired in the high grade DWMH group. Scores of BADS subtests showed no significant difference, but the age-matched standardized score was significantly low in the high grade DWMH group. Pathological findings showed that the greater the spread of DWMH, the more ischemia on cerebral whitematter progressed. In this study, we found that patients with severe subcortical ischemia may have impaired executive functions. These results might be conducted by the pathological features of DWMH.",,"Matsumoto, T.;Kato, H.;Hasegawa, A.;Utsumi, H.",2008,January,,0,
2618,A case of early stage CADASIL showing only dizziness and vertigo with a novel mutation of Notch 3 gene,"We report a 39-year-old woman who presented with only dizziness and vertigo for 2 months. Neurological examination revealed no abnormalities except for hypereflexia on the left side extremities. Neurootological examination revealed no abnormalities. MRI of the brain demonstrated patchy hyperintensity areas on FLAIR images in the periventricular white matter and external capsule. Her grandmother had cerebral infarction and her father is suffering from multi-infarct dementia. Her second older sister who similarly had dizziness and vertigo demonstrated similar MRI findings characterized by patchy hyperintensity areas in the white matter and external capsule even though she had no risk factors for atherosclerosis. Her third older sister also had dizziness and vertigo and had patchy hyperintensity areas in the white matter in her brain MRI even though she had no risk factors for atherosclerosis. Based on this family history, we suspected that she had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mutational analysis of Notch3 gene disclosed a novel missense mutation substituting arginine for cysteine at codon 206 (C206R) in exon 4 of the Notch3 gene, confirming the diagnosis of CADASIL. Interestingly, similar dizziness and vertigo were present not only in the patient, but also in the other two sisters who had the same gene mutation as the patient. This report supports the idea that the external capsule lesion is one of the signs suggestive of CADASIL as a diagnosis.",,"Matsumoto, H.;Tsumoto, M.;Yamamoto, T.;Takahashi, K.;Tahira, T.;Ugawa, Y.;Tsuji, S.",2005,January,,0,
2619,Intracranial compartment volumes in patients with enlarged ventricles assessed by magnetic resonance-based image processing,"Magnetic resonance image based computerized segmentation was used to measure the volumes of the brain, gray and white matter components, and to identify regions with prolonged enhancement on T(2)-weighted imaging, such as periventricular or deep white matter hyperintensities. The authors also determined the volumes of the ventricles and subarachnoid space in control subjects and in patients with: 1) aqueductal stenosis (AS); 2) other causes of obstructive hydrocephalus (OH); 3) Alzheimer's disease (AD); and 4) normal-pressure hydrocephalus (NPH). In AS the volume of the brain was smaller, whereas that of ventricles and subarachnoid cerebrospinal fluid space was larger than that of controls. The decrease in brain volume was due primarily to white matter loss. Although in OH the ventricles were larger, the subarachnoid space was smaller than in controls, presumably due to encroachment by the brain, in which the volume remained unchanged. In AD, loss of both gray and white matter resulted in a smaller brain volume, whereas that of ventricles and subarachnoid space was larger than in controls. In NPH patients, only ventricular volume was greater, whereas all other compartments were similar to controls. The brain normally occupies 87% to 92% of the intracranial volume and consequently, as observed in our patients, relatively small decrements in brain size lead to large increments in ventricular and/or extraventricular volumes. The magnitude of such changes differed markedly among our patient groups, and whether such changes prove useful clinical assessment and differentiation needs to be determined.",,"Matsumae, M.;Kikinis, R.;Mórocz, I.;Lorenzo, A. V.;Albert, M. S.;Black, P. M.;Jolesz, F. A.",1996,June,,0,
2620,Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's disease,"BACKGROUND: Cerebrovascular disease is common in Alzheimer's disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. OBJECTIVE: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. METHODS: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 +/- 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. RESULTS: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 +/- 4.5 micromol/l) were significant ly elevated compared with the AD without SBIs (11.7 +/- 4.7 micromol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 micromol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74-12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid beta-peptide(1-42) levels were not significantly correlated with pHcy levels in AD. CONCLUSION: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.",Aged;Alleles;Alzheimer Disease/ complications/ epidemiology;Amyloid beta-Peptides/cerebrospinal fluid;Apolipoproteins E/genetics;Cell Death/physiology;Cerebral Infarction/ epidemiology/ etiology;Enzyme-Linked Immunosorbent Assay;Female;Folic Acid/blood;Genotype;Homocysteine/ blood;Humans;Magnetic Resonance Imaging;Male;Neurons;Peptide Fragments/cerebrospinal fluid;Risk Factors;Vitamin B 12/blood;tau Proteins/cerebrospinal fluid,"Matsui, T.;Nemoto, M.;Maruyama, M.;Yuzuriha, T.;Yao, H.;Tanji, H.;Ootsuki, M.;Tomita, N.;Matsushita, S.;Higuchi, S.;Yoshida, Y.;Seki, T.;Iwasaki, K.;Furukawa, K.;Arai, H.",2005,,10.1159/000092316,0,
2621,Prefrontal cortex white matter tracts in prodromal Huntington disease,"Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large-scale analysis using multisite diffusion-weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT-HD study collected imaging and neuropsychological data on gene-positive HD participants without a clinical diagnosis (i.e., prodromal) and gene-negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto-occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG-age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long-range tracts essential for cross-region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage.",,"Matsui, J. T.;Vaidya, J. G.;Wassermann, D.;Kim, R. E.;Magnotta, V. A.;Johnson, H. J.;Paulsen, J. S.;Isabella De, S.;Shadrick, C.;Miller, A.;Edmond, C.;Preston, J.;Goh, A.;Antonopoulos, S.;Loi, S.;Chua, P.;Komiti, A.;Lynn, R.;Decolongon, J.;Fan, M.;Coleman, A.;Christopher, A. R.;Varvaris, M.;Ong, M.;Yoritomo, N.;Mallonee, W. M.;Suter, G.;Samii, A.;Freney, E. P.;Macaraeg, A.;Jones, R.;Wood-Siverio, C.;Factor, S. A.;Barker, R. A.;Mason, S.;Guzman, N. V.;McCusker, E.;Griffith, J.;Loy, C.;McMillan, J.;Gunn, D.;Orth, M.;Sübmuth, S.;Barth, K.;Trautmann, S.;Schwenk, D.;Eschenbach, C.;Quaid, K.;Wesson, M.;Wojcieszek, J.;Guttman, M.;Sheinberg, A.;Law, A.;Karmalkar, I.;Perlman, S.;Clemente, B.;Geschwind, M. D.;Sha, S.;Winer, J.;Satris, G.;Warner, T.;Burrows, M.;Rosser, A.;Price, K.;Hunt, S.;Marshall, F.;Chesire, A.;Wodarski, M.;Hickey, C.;Panegyres, P.;Lee, J.;Tedesco, M.;Maxwell, B.;Perlmutter, J.;Barton, S.;Smith, S.;Miedzybrodzka, Z.;Rae, D.;Vaughan, V.;D'Alessandro, M.;Craufurd, D.;Bek, J.;Howard, E.;Mazzoni, P.;Marder, K.;Wasserman, P.;Kumar, R.;Erickson, D.;Reeves, C.;Nickels, B.;Wheelock, V.;Kjer, L.;Martin, A.;Farias, S.;Martin, W.;Suchowersky, O.;King, P.;Wieler, M.;Sran, S.;Ahmed, A.;Rao, S.;Reece, C.;Bura, A.;Mourany, L.",2015,1,,0,
2622,Diffusion weighted imaging of prefrontal cortex in prodromal Huntington's disease,"Huntington's disease (HD) is a devastating neurodegenerative disease with no effective disease-modifying treatments. There is considerable interest in finding reliable indicators of disease progression to judge the efficacy of novel treatments that slow or stop disease onset before debilitating signs appear. Diffusion-weighted imaging (DWI) may provide a reliable marker of disease progression by characterizing diffusivity changes in white matter (WM) in individuals with prodromal HD. The prefrontal cortex (PFC) may play a role in HD progression due to its prominent striatal connections and documented role in executive function. This study uses DWI to characterize diffusivity in specific regions of PFC WM defined by FreeSurfer in 53 prodromal HD participants and 34 controls. Prodromal HD individuals were separated into three CAG-Age Product (CAP) groups (16 low, 22 medium, 15 high) that indexed baseline progression. Statistically significant increases in mean diffusivity (MD) and radial diffusivity (RD) among CAP groups relative to controls were seen in inferior and lateral PFC regions. For MD and RD, differences among controls and HD participants tracked with baseline disease progression. The smallest difference was for the low group and the largest for the high group. Significant correlations between Trail Making Test B (TMTB) and mean fractional anisotropy (FA) and/or RD paralleled group differences in mean MD and/or RD in several right hemisphere regions. The gradient of effects that tracked with CAP group suggests DWI may provide markers of disease progression in future longitudinal studies as increasing diffusivity abnormalities in the lateral PFC of prodromal HD individuals.","Adult;Anisotropy;Diffusion Magnetic Resonance Imaging/ methods;Disease Progression;Female;Humans;Huntington Disease/diagnosis/ pathology/psychology;Image Processing, Computer-Assisted/methods;Linear Models;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Prefrontal Cortex/ pathology;Psychiatric Status Rating Scales","Matsui, J. T.;Vaidya, J. G.;Johnson, H. J.;Magnotta, V. A.;Long, J. D.;Mills, J. A.;Lowe, M. J.;Sakaie, K. E.;Rao, S. M.;Smith, M. M.;Paulsen, J. S.",2014,Apr,10.1002/hbm.22273,0,
2623,Wisconsin Card Sorting Test in Parkinson's disease: diffusion tensor imaging,"INTRODUCTION: It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. MATERIALS AND METHODS: Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. RESULTS: There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was <or=2 relative to the group that achieved >2. CONCLUSION: Accumulating evidence suggests that conventional 'frontal' tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.","Aged;Anisotropy;Attention;Brain/ pathology/ physiopathology;Cognition Disorders/ diagnosis/etiology/ physiopathology;Diffusion Magnetic Resonance Imaging;Female;Frontal Lobe/pathology/physiopathology;Functional Laterality;Humans;Male;Memory;Nerve Fibers, Myelinated/pathology;Neural Pathways/pathology/physiopathology;Neuropsychological Tests;Parietal Lobe/pathology/physiopathology;Parkinson Disease/complications/ physiopathology/psychology;Thinking","Matsui, H.;Nishinaka, K.;Oda, M.;Niikawa, H.;Komatsu, K.;Kubori, T.;Udaka, F.",2007,Aug,10.1111/j.1600-0404.2006.00795.x,0,
2624,Intracranial dural arteriovenous fistula (DAVF) presenting progressive dementia and parkinsonism,"We studied three patients with dural arteriovenous fistula (DAVF). Major Symptoms were progressive dementia and parkinsonism, both of which progressed in step-wise fashion. Two of the three patients showed diffuse cerebral White matter lesions on brain CT and MRI. Progressive dementia and parkinsonism in our patients could be caused by diffuse cerebral parenchymal disturbance: impaired cerebral circulation due to severe venous hypertension. DAVF is important for the differential diagnosis in patients with progressive dementia and parkinsonism.",adult;aged;article;brain arteriovenous malformation;carotid arteriography;case report;computer assisted tomography;dementia;female;human;male;nuclear magnetic resonance imaging;Parkinson disease;priority journal,"Matsuda, S.;Waragai, M.;Shinotoh, H.;Takahashi, N.;Takagi, K.;Hattori, T.",1999,,,0,
2625,Cerebral hemodynamics in patients with normal pressure hydrocephalus: correlation between cerebral circulation time and dementia,"Regional cerebral blood flow and regional cerebral circulation time were measured in 13 demented patients with chronic hydrocephalus, mostly normal pressure hydrocephalus. The average hemispheric, frontal, and temporal cerebral blood flows were significantly reduced. The average regional cerebral circulation time values were significantly prolonged in the frontal, temporal, and thalamic regions, most markedly in the frontal white matter, where periventricular lucency was observed on computed tomography. Clinical improvement was obtained in all patients after operation. While postoperative regional cerebral blood flow values did not change compared with preoperative ones, postoperative regional cerebral circulation time values were significantly reduced in all the regions measured, and most markedly in the frontal white matter. The present results suggest that microcirculation in the frontal lobe is closely correlated with dementia in association with pressure exerted on the nerve fibers in the frontal white matter in patients with normal pressure hydrocephalus.","Aged;Blood Flow Velocity;*Cerebrovascular Circulation;Dementia/*physiopathology/radiography/surgery;Female;Frontal Lobe/physiopathology/radiography;Humans;Hydrocephalus, Normal Pressure/*physiopathology/radiography;Male;Middle Aged;Time Factors;Tomography, X-Ray Computed","Matsuda, M.;Nakasu, S.;Nakazawa, T.;Handa, J.",1990,Dec,,0,
2626,Volumetry of cerebral gray and white matter using VSRAD<sup>®</sup>,"Voxel-based morphometry (VBM) using structural brain MRI has been widely used for the early and differential diagnosis and evaluation of disease progression in neuropsychiatric diseases. VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions; anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping and smoothing; and finally performing statistical analysis. Stand-alone VBM software using SPM8 plus DARTEL running on Windows (Voxel-based Specific Regional analysis system for Alzheimer's disease, VSRAD<sup>®</sup>) has been developed as an adjunct to the clinical assessment. This software provides a Z-score map as a result of the comparison of the patient's MRI with a normal database.",,"Matsuda, H.",2015,1,,0,
2627,Voxel-based Morphometry of Brain MRI in Normal Aging and Alzheimer's Disease,"Voxel-based morphometry (VBM) using structural brain MRI has been widely used for assessment of normal aging and Alzheimer's disease (AD). VBM of MRI data comprises segmentation into gray matter, white matter, and cerebrospinal fluid partitions, anatomical standardization of all the images to the same stereotactic space using linear affine transformation and further non-linear warping, smoothing, and finally performing a statistical analysis. Two techniques for VBM are commonly used, optimized VBM using statistical parametric mapping (SPM) 2 or SPM5 with non-linear warping based on discrete cosine transforms and SPM8 plus non-linear warping based on diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL). In normal aging, most cortical regions prominently in frontal and insular areas have been reported to show age-related gray matter atrophy. In contrast, specific structures such as amygdala, hippocampus, and thalamus have been reported to be preserved in normal aging. On the other hand, VBM studies have demonstrated progression of atrophy mapping upstream to Braak's stages of neurofibrillary tangle deposition in AD. The earliest atrophy takes place in medial temporal structures. Stand-alone VBM software using SPM8 plus DARTEL running on Windows has been newly developed as an adjunct to the clinical assessment of AD. This software provides a Z-score map as a consequence of comparison of a patient's MRI with a normal database.",,"Matsuda, H.",2013,Feb,,0,
2628,"A 83 year old woman with dementia, gait disturbance, and convulsion","We report a 83 year old woman with dementia. She was apparently well until December of 1993 when she was 81 year old. At that time, she was operated on her cataract. Her post operative course was uneventful, however, shortly after her operation, she had an onset of memory loss and abnormal behavior. She showed a fluctuating course in her mental disturbance. In 1995, her dementia worsened with nocturnal agitation. She was admitted to our service on June 12, 1995. She was alert and her blood pressure was 140/100 mmHg. She showed recent memory loss and disorientation to time. Motor wise, she was unable to stand unsupported. Her gait with support showed small steps and a wide base. She was bradykinetic and ataxic in her finger to nose and heel to knee test, however, no rigidity or tremor was noted. Her MRI showed T2 high signal lesions in both medial thalamic areas, in the right occipital lobe, and in the bilateral cerebral white matters as well as in the basal ganglia. She was discharged for out-patient follow up on July 3, 1995. Four days after the discharge, she showed declining responses to stimuli and she developed dyspnea on July 14, 1995. She was admitted again on the same day. Her body temperature was 38.5°C and moist rales were hear in the left lung field. She appeared drowsy and no verbal response was obtained; no apparent motor palsy was noted. Blood count showed leukocytosis (14,300/ml). Blood gas analysis under 61 of oxygen inhalation through a mask was as follows: pH 7.460, PCO2 39.6 mmHg, PO2 67 mmHg, and HCO3 28.5 mEq/l. Two days after admission, she developed a convulsion in her left arm and she became unconscious. Her EEG showed periodically recurring lateralized epileptic discharges on the right fronto central areas. Her subsequent course was complicated by status epilepticus and respiratory distress. She died on July 26, 1995. She was discussed in a neurological CPC. The chief discussant arrived at a conclusion that she suffered from multi infarct dementia. Bilateral thalamic infarctions were considered to have played a significant role in her dementia. Post mortem examination revealed subcortical leukoencephalopathy of Binswanger's type and cerebral infarctions in the thalamic and basal ganglia regions and in the right occipital lobe. In addition, she showed isolated angitis of the central nervous system involving mainly in the small arteries located in the superficial areas of the brain and the spinal cord. This patient was interesting in that despite relatively mild leukoaraiosis in MRI, post mortem examination revealed profound pathologic changes in the subcortical white matters. In addition, she showed the isolated angitis of the CNS. The cause and the clinical correlates of her angitis were unclear.",aged;article;Binswanger encephalopathy;brain vasculitis;case report;convulsion;dementia;differential diagnosis;female;gait;histopathology;human;image analysis;lymphomatosis;nuclear magnetic resonance imaging,"Matsubayashi, S.;Sato, K. I.;Takase, M.;Mori, H.;Suda, K.;Kondo, T.;Mizuno, Y.",1997,,,0,
2629,The partial volume effect in the quantification of 1H magnetic resonance spectroscopy in Alzheimer's disease and aging,"1H-MRS variability increases due to normal aging and also as a result of atrophy in grey and white matter caused by neurodegeneration. In this work, an automatic process was developed to integrate data from spectra and high-resolution anatomical images to quantify metabolites, taking into account tissue partial volumes within the voxel of interest avoiding additional spectra acquisitions required for partial volume correction. To evaluate this method, we use a cohort of 135 subjects (47 male and 88 female, aged between 57 and 99 years) classified into 4 groups: 38 healthy participants, 20 amnesic mild cognitive impairment patients, 22 multi-domain mild cognitive impairment patients, and 55 Alzheimer's disease patients. Our findings suggest that knowing the voxel composition of white and grey matter and cerebrospinal fluid is necessary to avoid partial volume variations in a single-voxel study and to decrease part of the variability found in metabolites quantification, particularly in those studies involving elder patients and neurodegenerative diseases. The proposed method facilitates the use of 1H-MRS techniques in statistical studies in Alzheimer's disease, because it provides more accurate quantitative measurements, reduces the inter-subject variability, and improves statistical results when performing group comparisons.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/cerebrospinal fluid/ pathology;Analysis of Variance;Aspartic Acid/analogs & derivatives/metabolism;Brain/metabolism/ pathology;Female;Functional Laterality;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy/methods;Male;Middle Aged;Mild Cognitive Impairment/pathology;Protons","Mato Abad, V.;Quiros, A.;Garcia-Alvarez, R.;Loureiro, J. P.;Alvarez-Linera, J.;Frank, A.;Hernandez-Tamames, J. A.",2014,,10.3233/jad-140582,0,
2630,A Comparative Study of CSF Viral RNA Loads between HIV Positive Patients with Neurological Manifestations and Neurologically Asymptomatic HIV Patients,"INTRODUCTION: There are conflicting reports in literature about correlation of CSF viral RNA levels with neurological manifestations in HIV positive patients. Many studies in animals and human subjects have shown that CSF HIV-1 RNA can be useful as a specific marker of HIV induced neuropathology. To the contrary there are studies which show that neurological disease states can occur in absence of significant increase of CSF HIV RNA. MATERIALS AND METHODS: This was a prospective study conducted at Base hospital Delhi Cantt, New Delhi, a tertiary care hospitals for HIV patients. The study period was from 16 May 2006 to16 Jun 2011. The current study included forty (40) patients (Twenty HIV positive patients with neurological manifestations and twenty HIV positive patients clinically without any neurological manifestation). All potential study subjects and controls were explained the nature of this study and enrolled thereafter with written consent. RESULTS: In our study all the cases (HIV/AIDS patients with Neuro AIDS) and controls (HIV/AIDS patients without Neuro manifestations) were males only. 45% of the cases and 60% of controls were in the age group of 25 to 35 yrs and 35 % of cases and 40% of controls were in age group of 36 to 45 yrs. Among cases (HIV patients with neurological manifestations), The neurological manifestations in our 20 patients included; dementia-5, cryptococcal meningitis-4, Tubercular meningitis-4, CVA-3, Headache-3, (without CSF abnormality), 1 case each of pyogenic meningitis, Candida meningitis, Tremors and Herpes Zoster. Among the 20 cases fourteen patients had abnormal CSF (70%) whereas only one patient among the controls showed CSF abnormality (5%). Out of 20 cases, radio-imaging (CT Scan/ MRI) of brain was done in 18 cases. Twelve cases (66.66) had some abnormality on CT/ MRI. Various abnormalities seen were as under Calcified granuloma-1, Infarcts-5, Hydrocephalus-2, TBM (meningeal enhancement)-2, Candidiasis (Focal hypodensities in subcortical white matter of cerebral hemispheres)-1, Cryptococcoma-1, Cerebral atrophy-1, Focal enhancing lesions-2. In our study, mean CSF viral load in cases was 5236.3 copies/ml and in controls 502.4 copies/ml. Viral load in CSF among cases was significantly higher than viral load in CSF among controls. CONCLUSIONS: CSF HIV-1 RNA viral load estimation can be a useful tool for clinicians in confirming neurological involvement in HIV infected patients. Hence, in HIV positive patients suspected to have neurological involvement, CSF viral load studies should be done. Serial estimations of CSF HIV-1 RNA levels can be of prognostic significance. Estimation of CSF HIV-1 RNA level before and serially during administration of HAART can be useful to judge the efficacy of HAART.",,"Mathur, A. D.;Devesh, S.",2017,Aug,,0,
2631,Reduced neuropsychological test performance in asymptomatic carotid stenosis: The Tromso Study,"OBJECTIVE: To assess the relationship between asymptomatic carotid stenosis, neuropsychological test performance, and silent MRI lesions. METHODS: Performance on several neuropsychological tests was compared in 189 subjects with ultrasound-assessed carotid stenosis and 201 control subjects without carotid stenosis, recruited from a population health study. Subjects with a previous history of stroke were excluded. The test battery included tests of attention, psychomotor speed, memory, language, speed of information processing, motor functioning, intelligence, and depression. Sagittal T1-weighted and axial and coronal T2-weighted spin echo MRI was performed, and presence of MRI lesions (white matter hyperintensities, lacunar and cortical infarcts) was recorded. RESULTS: Subjects with carotid stenosis had significantly lower levels of performance in tests of attention, psychomotor speed, memory, and motor functioning, independent of MRI lesions. There were no significant differences in tests of speed of information processing, word association, or depression. Cortical infarcts and white matter hyperintensities were equally distributed among persons with and without carotid stenosis. Lacunar infarcts were more frequent in the stenosis group (p = 0.03). CONCLUSIONS: Carotid stenosis was associated with poorer neuropsychological performance. This could not be explained by a higher proportion of silent MRI lesions in persons with asymptomatic carotid stenosis, making it less likely that the cognitive impairment was caused by silent emboli.","Aged;Aged, 80 and over;Brain/pathology;Carotid Arteries/ultrasonography;Carotid Stenosis/diagnosis/*physiopathology;*Cognition;Cross-Sectional Studies;Dementia, Multi-Infarct;Dementia, Vascular/diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;*Psychomotor Performance;Ultrasonography, Doppler","Mathiesen, E. B.;Waterloo, K.;Joakimsen, O.;Bakke, S. J.;Jacobsen, E. A.;Bonaa, K. H.",2004,Mar 9,,0,
2632,Subcortical arteriosclerotic encephalopathy: Binswanger's disease,"Binswanger, in his 1894 dissertation on the differential diagnosis of general paresis of the insane, described a slowly progressive dementia associated with macroscopic loss of white matter. In recent years interest in Binswanger's disease was rekindled with CT demonstration of extensive white matter low densities in some patients. To define the clinical spectrum, we reviewed 22 consecutive cases in which the CT appearances suggested a diagnosis of Binswanger's disease. Two patients had focal neurological deficits at presentation, but recent anoxic or hypoglycaemic insults could not be excluded as the cause of the CT abnormalities. The 20 remaining patients were demented and showed variable combinations of corticobulbar dysfunction and gait dyspraxia. The duration of symptoms ranged from a few months to several years. Sixty per cent of this group gave a history of discrete stroke events and focal cortical and/or lacunar infarcts were a frequent CT finding. Binswanger's disease is probably due to chronic or acute-on-chronic white matter ischaemia. The association with lacunar and cortical infarctions suggests that a combination of large and small vessel disease produces diffuse ischaemia maximal in white matter watershed zones. Binswanger's disease is clinically differentiated from multi-infarct dementia by its time course.","Aged;Aged, 80 and over;Cerebral Infarction/radiography;Dementia/radiography;Female;Humans;Intracranial Arteriosclerosis/*radiography;Male;Middle Aged;Risk Factors;*Tomography, X-Ray Computed","Mathers, S. E.;Chambers, B. R.;Merory, J. R.;Alexander, I.",1987,,,0,
2633,Sporadic leucodystrophy with neuroaxonal spheroids: Persistence of DWI changes and neurocognitive profiles: A case study,"Leucodystrophy with neuroaxonal spheroids (LNS) is rare. There have been fewer than 10 sporadic cases reported, all occurring in the fourth to sixth decades of life. Previously unreported diffusion weighted imaging (DWI) changes on brain imaging in LNS are described as well as the first neurocognitive profile of this disorder in a 24-year-old woman. Neuropsychological testing demonstrated a global cognitive decline, with deficits most representative of a frontal-subcortical dementia. Bright DWI and corresponding dark apparent diffusion coefficient changes were initially mistaken for acute cerebral infarction but then persisted for 19 weeks. Biopsy of a bright DWI lesion showed no evidence of vascular disease and confirmed this rare diagnosis. Given the number of patients with the diagnosis of cerebrovascular disease, supported by DWI findings, we propose other milder cases of LNS may be overlooked.",,"Mateen, F. J.;Keegan, B. M.;Krecke, K.;Parisi, J. E.;Trenerry, M. R.;Pittock, S. J.",2010,June,,0,
2634,Environmental and Clinical Risk Factors for Delirium in a Neurosurgical Center: A Prospective Study,"BACKGROUND: Few reports of delirium-related risk factors have focused on environmental risk factors and clinical risk factors, such as white matter signal abnormalities on magnetic resonance imaging fluid attenuated inversion recovery images. METHODS: We prospectively enrolled 253 patients admitted to our neurosurgical center between December 2014 and June 2015 and analyzed 220 patients (100 male patients; mean age, 64.1 years; age range, 17-92 years). An Intensive Care Delirium Screening Checklist score >/=4 points indicated delirium. We evaluated patient factors consisting of baseline characteristics and related factors, such as white matter lesions (WMLs), as well as the surrounding environment. RESULTS: Delirium occurred in 29/220 cases (13.2%). Regarding baseline characteristics, there were significant statistical correlations between delirium and age (P = 0.0187), Hasegawa Dementia Scale-Revised score (P = 0.0022) on admission, and WMLs (P < 0.0001). WMLs were related to age (P < 0.0001) and atherosclerotic disease (P = 0.004). Regarding related factors, there were significant statistical correlations between delirium and stay in a neurosurgical care unit (P = 0.0245). Multivariate logistic regression analyses showed statistically significant correlations of delirium with WMLs (P < 0.0001) and surrounding patients with delirium (P = 0.026). CONCLUSIONS: WMLs in patients and the surrounding environment are risk factors for delirium in a neurosurgical center. To prevent delirium, clinicians must recognize risk factors, such as high-grade WMLs, and manage environmental factors.","Adolescent;Adult;Aged;Aged, 80 and over;Cerebral Hemorrhage/complications;Cerebral Infarction/complications;Craniocerebral Trauma/complications;Delirium/ etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Risk Factors;Subarachnoid Hemorrhage/complications;Surgicenters/statistics & numerical data;Young Adult;Delirium;Environmental;Neurosurgical center;Risk factor;White matter signal abnormalities","Matano, F.;Mizunari, T.;Yamada, K.;Kobayashi, S.;Murai, Y.;Morita, A.",2017,Jul,,0,
2635,Canavan disease: From spongy degeneration to molecular analysis,"Establishing the basic defect in Canavan disease has led to reliable biochemical methods for the diagnosis of this disease. The isolation of the gene and identification of mutations causing Canavan disease have led to the possibility of using DNA methods for the diagnosis of Canavan disease and for carder detection. A surprising finding is the high carder frequency of this gene defect among Ashkenazi Jewish people. Analysis for two mutations leads to the identification of 97% of Jewish patients with Canavan disease, and screening of Ashkenazi Jews is possible. N-Acetylaspartic acid has been considered to be an inert compound. The pathophysiology of Canavan disease links lack of NAA hydrolysis to a severe, debilitating white matter disease. Currently, NAA is being studied in many other brain disorders, such as Alzheimer disease, Huntington disease, and stroke. However, the only disease with a specific defect in the metabolism of NAA is Canavan disease. An animal model for Canavan disease is needed to study some of the questions regarding the role of NAA in brain tissue, and for the study of therapeutic modalities, including gene therapy.",n acetylaspartic acid;article;autosomal disorder;Canavan disease;child;clinical feature;histopathology;human;leukodystrophy;nuclear magnetic resonance imaging;priority journal,"Matalon, R.;Michals, K.;Kaul, R.",1995,,,0,
2636,Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum,"We investigated common structural and network changes across the sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD) continuum. Based on cluster analysis using the frontotemporal assessment battery, 51 patients with sporadic ALS were subdivided into three groups: 25 patients with ALS with cognitive deficiency (ALS-CD); seven patients who satisfied FTD criteria (ALS-FTD), and 19 patients with ALS with normal cognitive function (ALS-NC). Compared with the controls, gray matter images from patients with ALS-FTD showed atrophic changes in the following order of severity: caudate head, medial frontal gyrus, thalamus, amygdala, putamen, and cingulate gyrus (peak level, uncorrected p < 0.001). The caudate head was significant at the cluster level using FWE correction (p < 0.05). Diffusion tensor imaging with tract-based spatial statistics revealed white matter changes in the areas surrounding the caudate head, the internal capsule, and the anterior horn of the lateral ventricle in the ALS-CD and ALS-FTD. Probabilistic diffusion tractography showed a significant decrease in structural connectivity between the caudate head and the dorsomedial frontal cortex and the lateral orbitofrontal cortex, even in the ALS-NC. Our results indicated that the caudate head and its networks were the most vulnerable to lesion in sporadic ALS-FTD-spectrum patients associated with cognitive decline with FTD features.","Aged;Amyotrophic Lateral Sclerosis/ complications/diagnostic imaging/ pathology;Analysis of Variance;Anisotropy;Caudate Nucleus/diagnostic imaging/ pathology;Cognition Disorders/ etiology;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/ complications/diagnostic imaging/ pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neural Pathways/ pathology;Retrospective Studies;Voxel-based morphometry (VBM);amyotrophic lateral sclerosis (ALS);frontotemporal dementia (FTD);probabilistic diffusion tractography;tract-based spatial statistics (TBSS)","Masuda, M.;Senda, J.;Watanabe, H.;Epifanio, B.;Tanaka, Y.;Imai, K.;Riku, Y.;Li, Y.;Nakamura, R.;Ito, M.;Ishigaki, S.;Atsuta, N.;Koike, H.;Katsuno, M.;Hattori, N.;Naganawa, S.;Sobue, G.",2016,Oct - Nov,,0,2637
2637,Involvement of the caudate nucleus head and its networks in sporadic amyotrophic lateral sclerosis-frontotemporal dementia continuum,"We investigated common structural and network changes across the sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD) continuum. Based on cluster analysis using the frontotemporal assessment battery, 51 patients with sporadic ALS were subdivided into three groups: 25 patients with ALS with cognitive deficiency (ALS-CD); seven patients who satisfied FTD criteria (ALS-FTD), and 19 patients with ALS with normal cognitive function (ALS-NC). Compared with the controls, gray matter images from patients with ALS-FTD showed atrophic changes in the following order of severity: caudate head, medial frontal gyrus, thalamus, amygdala, putamen, and cingulate gyrus (peak level, uncorrected p < 0.001). The caudate head was significant at the cluster level using FWE correction (p < 0.05). Diffusion tensor imaging with tract-based spatial statistics revealed white matter changes in the areas surrounding the caudate head, the internal capsule, and the anterior horn of the lateral ventricle in the ALS-CD and ALS-FTD. Probabilistic diffusion tractography showed a significant decrease in structural connectivity between the caudate head and the dorsomedial frontal cortex and the lateral orbitofrontal cortex, even in the ALS-NC. Our results indicated that the caudate head and its networks were the most vulnerable to lesion in sporadic ALS-FTD-spectrum patients associated with cognitive decline with FTD features.",amygdaloid nucleus;amyotrophic lateral sclerosis;capsula interna;caudate nucleus;cingulate gyrus;cluster analysis;cognitive defect;controlled study;diffusion tensor imaging;frontotemporal dementia;gray matter;head;human;lateral brain ventricle;lateral orbitofrontal cortex;major clinical study;middle frontal gyrus;putamen;spinal cord ventral horn;statistics;thalamus,"Masuda, M.;Senda, J.;Watanabe, H.;Epifanio, B.;Tanaka, Y.;Imai, K.;Riku, Y.;Li, Y.;Nakamura, R.;Ito, M.;Ishigaki, S.;Atsuta, N.;Koike, H.;Katsuno, M.;Hattori, N.;Naganawa, S.;Sobue, G.",2016,,,0,
2638,Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study,"INTRODUCTION: Extract of Ginkgo biloba (EGb), a dietary supplement used for a number of conditions including dementia, has been suggested to increase cerebral bloodflow (CBF). The purpose of this study was to determine if changes in CBF could be detected by dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI)in elderly human subjects taking EGb. METHODS: DSC-MRI was performed in nine healthy men(mean age 61+/-10 years) before and after 4 weeks of 60 mg EGb taken twice daily. One subject underwent six consecutive scans to evaluate intrasubject reproducibility. CBF values were computed before and after EGb, and analyzed at three different levels of spatial resolution, using voxel-based statistical parametric mapping (SPM), and regions of interest in different lobes, and all regions combined. RESULTS: Normalized intrasubject CBF (nCBF) measurements had a standard deviation of 7% and 4% in gray and white matter (WM) regions, respectively. SPM using an uncorrected, voxel-level threshold of P</=0.001 showed a small CBF increase in the left parietal-occipital region.CBF in individual lobar regions did not show any significant change post-EGb, but all regions combined showed a significant increase of non-normalized CBF after EGb (15% in white and 13% in gray matter, respectively, P</=0.0001). CONCLUSION: nCBF measured by DSC-MRI has good intrasubject reproducibility. In this small cohort of normal elderly individuals, a mild increase in CBF is found in the left parietal-occipital WM after EGb, as well as a small but statistically significant increase in global CBF.",Blood Flow Velocity/drug effects/physiology;Cerebrovascular Circulation/ drug effects/ physiology;Ginkgo biloba/ chemistry;Humans;Magnetic Resonance Angiography/ methods;Male;Middle Aged;Pilot Projects;Plant Extracts/ pharmacology,"Mashayekh, A.;Pham, D. L.;Yousem, D. M.;Dizon, M.;Barker, P. B.;Lin, D. D.",2011,Mar,10.1007/s00234-010-0790-6,0,
2639,White matter lesions predispose to falls in older people,,"Accidental Falls/*mortality;Aged;Aged, 80 and over;Cerebral Arteries/pathology/physiopathology;Cerebrum/blood supply/*pathology/physiopathology;Cohort Studies;Comorbidity;Dementia, Vascular/epidemiology/pathology/physiopathology;Disability Evaluation;Disease Progression;Female;Gait/physiology;Gait Disorders, Neurologic/*epidemiology/*pathology/physiopathology;Humans;Incidence;Leukoaraiosis/*epidemiology/*pathology/physiopathology;Magnetic Resonance Imaging;Male;Muscle Weakness/diagnosis/epidemiology/physiopathology;Neurologic Examination;Prospective Studies;Quadriceps Muscle/physiopathology;Risk Factors","Masdeu, J. C.;Wolfson, L.",2009,Sep,10.1161/strokeaha.109.558122,0,
2640,Diffusion Tensor Imaging to Map Brain Microstructural Changes in CADASIL,"BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is sensitive to brain microstructural changes. The aims of this DTI study were to map voxelwise the spatial distribution of brain microstructural changes in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to investigate any correlation between DTI-derived indices and extension of T2 hyperintensity. METHODS: Eighteen patients with CADASIL and 18 age-, sex-, and education-level-matched healthy controls underwent magnetic resonance imaging at 3 T. Differences in DTI-derived indices (mean diffusivity [MD], fractional anisotropy [FA], axial [AD] and radial [RD] diffusivities, and mode of anisotropy [MO]) of brain white matter (WM) between CADASIL patients and healthy subjects were assessed through tract-based spatial statistics. Then, DTI-derived indices were correlated with the patient's score on the extended Fazekas visual scale of the T2 hyperintensity. RESULTS: When compared to healthy controls, CADASIL patients showed extensive symmetric areas of increased MD/RD and decreased AD/FA/MO that involved almost the entire hemispheric cerebral WM (internal and external capsule, WM of the temporal poles, superior and inferior longitudinal fasciculus, inferior frontal-occipital fasciculus, uncinate fasciculus, cingulum, forceps major and minor, corticospinal tracts, and thalamic radiations), thalami, and corpus callosum. Additional areas of increased RD were observed in pons, midbrain, cerebellar peduncles, and cerebellar WM. Only FA was negatively correlated with extended Fazekas visual score. CONCLUSIONS: Our results indicate that brain damage in CADASIL is associated with extensive microstructural changes implying impairment of intra- and inter-hemispheric cerebral, thalamocortical, and cerebrocerebellar connections. Severity of microstructural changes correlates with extension of T2 hyperintensity.",Adult;Aged;Brain/blood supply/ diagnostic imaging;Brain Diseases/ diagnostic imaging/pathology;Brain Mapping;CADASIL/ diagnostic imaging/ pathology;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Young Adult;Cadasil;small vessel disease;tract-based spatial statistics,"Mascalchi, M.;Pantoni, L.;Giannelli, M.;Valenti, R.;Bianchi, A.;Pracucci, G.;Orsolini, S.;Ciulli, S.;Tessa, C.;Poggesi, A.;Pescini, F.;Inzitari, D.;Diciotti, S.",2017,Jan,,0,
2641,Diffusion Tensor Imaging to Map Brain Microstructural Changes in CADASIL,"BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is sensitive to brain microstructural changes. The aims of this DTI study were to map voxelwise the spatial distribution of brain microstructural changes in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to investigate any correlation between DTI-derived indices and extension of T2 hyperintensity. METHODS: Eighteen patients with CADASIL and 18 age-, sex-, and education-level-matched healthy controls underwent magnetic resonance imaging at 3 T. Differences in DTI-derived indices (mean diffusivity [MD], fractional anisotropy [FA], axial [AD] and radial [RD] diffusivities, and mode of anisotropy [MO]) of brain white matter (WM) between CADASIL patients and healthy subjects were assessed through tract-based spatial statistics. Then, DTI-derived indices were correlated with the patient's score on the extended Fazekas visual scale of the T2 hyperintensity. RESULTS: When compared to healthy controls, CADASIL patients showed extensive symmetric areas of increased MD/RD and decreased AD/FA/MO that involved almost the entire hemispheric cerebral WM (internal and external capsule, WM of the temporal poles, superior and inferior longitudinal fasciculus, inferior frontal-occipital fasciculus, uncinate fasciculus, cingulum, forceps major and minor, corticospinal tracts, and thalamic radiations), thalami, and corpus callosum. Additional areas of increased RD were observed in pons, midbrain, cerebellar peduncles, and cerebellar WM. Only FA was negatively correlated with extended Fazekas visual score. CONCLUSIONS: Our results indicate that brain damage in CADASIL is associated with extensive microstructural changes implying impairment of intra- and inter-hemispheric cerebral, thalamocortical, and cerebrocerebellar connections. Severity of microstructural changes correlates with extension of T2 hyperintensity.",brain damage;CADASIL;capsula interna;cerebellar peduncle;cingulum (brain);clinical article;controlled study;corpus callosum;diffusion tensor imaging;education;external capsule;forceps;fractional anisotropy;human;inferior longitudinal fasciculus;mesencephalon;pons;population based case control study;pyramidal tract;radiation;statistics;thalamus;uncinate fasciculus,"Mascalchi, M.;Pantoni, L.;Giannelli, M.;Valenti, R.;Bianchi, A.;Pracucci, G.;Orsolini, S.;Ciulli, S.;Tessa, C.;Poggesi, A.;Pescini, F.;Inzitari, D.;Diciotti, S.",2016,,,0,2640
2642,"Huntington disease: volumetric, diffusion-weighted, and magnetization transfer MR imaging of brain","PURPOSE: To investigate whether diffusion-weighted and magnetization transfer (MT) magnetic resonance (MR) imaging depict regional and/or global brain abnormalities in patients with Huntington disease (HD). MATERIALS AND METHODS: Twenty-one carriers of the HD mutation (mean age, 58 years +/- 11 [SD]) and 21 healthy control subjects (mean age, 54 years +/- 13) underwent conventional, diffusion-weighted, and MT MR imaging. Volumes, mean apparent diffusion coefficients (ADCs), and MT ratios (MTRs) for left and right caudate nucleus, putamen, and cerebral periventricular white matter-as well as an index of normalized brain volume and whole-brain ADC and MT histograms-were computed. Asymmetry in volume, ADC, and MTR measurements in caudate nucleus, putamen, and periventricular white matter in control subjects and HD carriers were evaluated with Wilcoxon testing for paired samples. Differences in MR imaging variables between HD carriers and control subjects were evaluated with Mann-Whitney U testing; correlations between stages of clinical severity and MR imaging data were investigated with Spearman rank correlation testing. RESULTS: No significant asymmetry was observed for any of the MR imaging variables. Caudate nucleus, putamen, and whole-brain volumes were smaller (P <.001 for all) in HD carriers than in control subjects. HD carriers also had increased ADC in the caudate nucleus (P =.002), putamen (P <. 001), cerebral periventricular white matter (P <.001), and whole brain (P <.001). MTR was not significantly different between HD carriers and control subjects. Correlation was observed between stages of increasing clinical disease severity and both decrease in volume of caudate nucleus (Spearman rho = -0.63), putamen (rho = -0.64), and whole brain (rho = -0.46) and increase in ADC in caudate nucleus (rho = 0.52), periventricular white matter (rho = 0.45), and whole brain (rho = 0.44). CONCLUSION: Regional and global volume loss in HD is accompanied by an increase in ADC; this correlates with disease severity.",Adult;Aged;Brain/ pathology;Female;Humans;Huntington Disease/ diagnosis;Magnetic Resonance Imaging/methods;Male;Middle Aged,"Mascalchi, M.;Lolli, F.;Della Nave, R.;Tessa, C.;Petralli, R.;Gavazzi, C.;Politi, L. S.;Macucci, M.;Filippi, M.;Piacentini, S.",2004,Sep,10.1148/radiol.2322030820,0,
2643,"Computed tomography, magnetic resonance imaging and pathological correlations in a case of Binswanger's disease","The results of 3 computed tomography (CT) examinations carried out over a 7 year period and of a post-mortem magnetic resonance (MR) study showed aspects of a white matter disease in a hypertensive patient suffering from vascular dementia. Histopathology revealed the primary cause of dementia to be a white matter degeneration sparing the U fibers. Rarefaction of both the myelin sheaths and the axons was present together with severe thickening of the medullary arteries. These findings support the existence of Binswanger's disease (BD) as a distinct variety of arteriosclerotic dementia. CT and MR imaging are valuable aids for diagnosis. However, since there are many other causes of CT and MR demonstrated diffuse white matter degeneration in the elderly, a conclusive diagnosis of BD requires pathological confirmation.",,"Mascalchi, M.;Inzitari, D.;Dal Pozzo, G.;Taverni, N.;Abbamondi, A. L.",1989,1989,,0,
2644,CT and MR imaging of neuroaxonal leukodystrophy presenting as early-onset frontal dementia,CT and MR imaging showed diffuse changes of the frontal white matter and genu of the corpus callosum with minimal atrophy and no contrast enhancement in a 41-year-old woman with progressive dementia. Brain biopsy disclosed axonal spheroids and gliosis in the white matter without macrophage or inflammatory infiltration or vessel abnormalities consistent with neuroaxonal leukodystrophy. This disease can be suspected on CT and MR imaging findings but requires neuropathologic examination to be diagnosed.,,"Mascalchi, M.;Gavazzi, C.;Morbin, M.;Giaccone, G.;Arnetoli, G.;Zappoli, R.;Bugiani, O.",2006,May,,0,
2645,Magnetic resonance imaging of degenerative diseases of the central nervous system,"MRI enables a better assessment than CT of the bulk loss, i.e. atrophy, which is a characteristic feature of all the degenerative diseases of CNS, at least in their advanced phases. Moreover, in several of these disorders, proton density, balanced and T2 weighted MR images can show symmetric areas of abnormally low or high signal intensity in the deep gray nuclei or white matter. Since these signal abnormalities are not specific of degenerative diseases of the CNS, their shape and distribution have to match those of the histopathological changes characteristic of each disease, before they could represent useful ancillary signs. Combination of the above MRI findings with appropriate clinical and laboratory features will however be crucial to the diagnosis in any single case.",,"Mascalchi, M.;Dal Pozzo, G.",1992,Dec,,0,
2646,Markers of brain illness may be hidden in your olfactory ability: a Japanese perspective,"There is evidence that impaired human cognitive abilities are reflected by loss of olfactory abilities. Declining olfactory perception may be a biomarker for impairment of cognitive function and of impending neurogenerative disorders. As olfactory perception may differ between culture and ethnic group, we sought to confirm this relationship with Japanese participants. In this study, we examined possible relationships between age and olfactory abilities in healthy Japanese subjects (control subjects) over a wide range of ages and compared this relationship with that observed in three neurodegenerative disorders; patients with Parkinson's disease (PD), Type 1 myotonic dystrophy (DM1) and Alzheimer's disease (AD). In control subjects, both threshold and recognition abilities decreased with age. Ability to detect odors was generally intact in most control subjects, however, we found that the abilities of individuals in the three different patient populations to recognize odors were impaired relative to control subjects. All three types of patients exhibited decreased or impaired odor-recognition compared with age-matched controls. Previous studies showed the causes of olfactory impairments in PD and AD patients were attributable to pathological changes and MRI signal abnormalities in limbic areas, including the amygdala (AMG), entorhinal cortex (ENT), hippocampus (HI), and orbitofrontal cortex (OFC). Another study reported that DM1 patients have bilateral lesions in anterior temporal areas, including the subcortical white matter, AMG, ENT and insula. Our findings underscore the need to pay careful attention to significant decreases of odor identification abilities caused by diverse forms of abnormal brain function, especially in the AMG, ENT and HI.","Adult;Aged;Aged, 80 and over;Aging/physiology;Alzheimer Disease/complications/*diagnosis/physiopathology;Brain/physiopathology;Female;Humans;Japan;Male;Middle Aged;Myotonic Dystrophy/complications/*diagnosis/physiopathology;Olfaction Disorders/complications/*diagnosis/physiopathology;Olfactory Perception/*physiology;Parkinson Disease/complications/*diagnosis/physiopathology;Sensory Thresholds/physiology;Smell/*physiology;Age trajectories;Alzheimer's disease;Olfactory detection;Olfactory recognition;Parkinson's disease;Type 1 myotonic dystrophy","Masaoka, Y.;Pantelis, C.;Phillips, A.;Kawamura, M.;Mimura, M.;Minegishi, G.;Homma, I.",2013,Aug 9,10.1016/j.neulet.2013.05.077,0,
2647,"A familial disorder with subcortical ischemic strokes, dementia, and leukoencephalopathy","A family had a disorder characterized by (1) a pattern suggestive of autosomal dominant inheritance, (2) recurrent attacks of focal brain deficits starting in mid adulthood and often leading to severe motor disability with pseudobulbar palsy and dementia of the subcortical type, and (3) neuroimaging evidence of leukoencephalopathy and well-circumscribed lesions consistent with small deep infarcts. Some affected members were clinically asymptomatic but had MRI signs of leukoencephalopathy. Extensive investigations failed to uncover a previously described recognizable genetic disorder.",adult;article;autosomal dominant inheritance;cerebrovascular accident;clinical article;clinical feature;computer assisted tomography;dementia;diagnostic imaging;familial disease;female;human;leukoencephalopathy;male;motor dysfunction;nuclear magnetic resonance imaging;pedigree;priority journal;recurrent disease,"Mas, J. L.;Dilouya, A.;De Recondo, J.",1992,,,0,
2648,Vascular parkinsonism,"Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup.?",Binswanger encephalopathy;cerebrovascular disease;cognitive defect;frontal lobe;gait;human;imaging;multiinfarct dementia;parkinsonism;urine incontinence;white matter lesion,"Marxreiter, F.;Winkler, J.",2016,,10.1055/s-0042-107076,0,2650
2649,[Vascular parkinsonism] Vaskulares Parkinson-Syndrom (= Parkinsonismus bei vaskularer Enzephalopathie),"Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup. .",,"Marxreiter, F.;Winkler, J.",2016,Jul,,0,
2650,[Vascular parkinsonism],"Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup. .",,"Marxreiter, F.;Winkler, J.",2016,Jul,10.1055/s-0042-107076,0,
2651,Cerebrospinal Fluid Tau Protein and Periventricular White Matter Lesions in Patients with Mild Cognitive Impairment: Implications for 2 Major Pathways,"Background: Mild cognitive impairment (MCI) may be a heterogeneous condition rather than a uniform disease entity. Objective: To develop reliable tools that aid in identifying patients at risk of developing Alzheimer disease (AD) among heterogeneous populations with MCI to maximize the benefits of emerging therapies for AD. Design: A 2-year prospective study. Setting: Clinical follow-up in an outpatient memory clinic. Patients: Seventy-two consecutive older patients with memory complaints. Main Outcome Measures: Cerebrospinal fluid tau levels, severity of periventricular and deep white matter lesions, silent brain infarction on magnetic resonance imaging, plasma homocysteine levels, apolipoprotein E genotype, and other vascular risk factors were assessed at baseline. Results: Fifty-seven patients were diagnosed as having amnestic MCI. Forty-one patients with (AD-converted MCI group) or without (progressive MCI group) conversion to dementia and AD progressed over time, whereas the other 16 patients remained cognitively stable (stable MCI group). The stable MCI group was characterized by normal cerebrospinal fluid tau levels and a high grade of periventricular white matter lesions (PWMLs). The progressive MCI and AD-converted MCI groups had increased cerebrospinal fluid tau levels and low grades of PWMLs. A logistic regression model showed that age was significantly associated with developing PWMLs (P=.03; odds ratio, 1.15; 95% confidence interval, 1.0-1.3). Conclusions: Tau-related AD pathologic conditions and possibly ischemic PWMLs represent 2 major etiologies in the development of MCI, reflecting heterogeneity in the clinical progression. Because the progressive type of MCI may be a primary target of clinical trials that aim at secondary prevention of dementia, these patients should be identified by appropriate biomarkers and neuroimaging techniques.",,"Maruyama, M.;Matsui, T.;Tanji, H.;Nemoto, M.;Tomita, N.;Ootsuki, M.;Arai, H.;Sasaki, H.",2004,May,,0,
2652,Acute encephalitis/encephalopathy associated with transient involuntary movement and limbic dysfunction in the recovery phase,"We report 3 patients aged 3-4 years who presented with impaired consciousness and status epilepticus or a cluster of seizures, followed by transient involuntary movements and limbic dysfunction in the recovery phase. In all the patients, the involuntary movements were observed mainly on the left side and consisted of dystonia, athetosis, chorea, facial myoclonus, and oral dyskinesia. The patients also showed stereotypic movement, oral tendency, visual agnosia, and emotional disturbance, which suggested limbic dysfunction resembling Klüver-Bucy syndrome. Single-photon emission computed tomography (SPECT) revealed hypoperfusion of the unilateral basal ganglia and the adjacent frontal and temporal lobes. No obvious lesions were observed on brain MRI in the acute phase in 2 patients, who recovered completely during the follow-up period. However, the last patient, who had abnormalities with regard to the limbic system and subcortical white matter on diffusion-weighted image in the acute phase, exhibited mental retardation, epilepsy, and persistent oral tendency during the follow-up period.",,"Maruyama, K.;Itomi, S.;Sofue, A.;Natsume, J.",2009,2009,,0,
2653,Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions,"Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41-year-old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β-amyloid precursor protein. In addition, scattered inactive demyelinating plaque-like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition. © 2011 Japanese Society of Neuropathology.",amyloid precursor protein;antibiotic agent;neurofilament protein;paracetamol;adult;adult onset leukodystrophy with neuroaxonal spheroid;Africa;antibiotic therapy;article;autopsy;behavior change;brain;brain calcification;brain damage;brain dysfunction;brain stem;case report;cervical spinal cord;chest infection;clinical feature;computer assisted tomography;contrast enhancement;demyelinating disease;disease association;female;frontal lobe;frontal lobe dysfunction;headache;histopathology;human;laboratory test;leukodystrophy;microscopy;Mini Mental State Examination;neuroaxonal dystrophy;neurofilament;neuroimaging;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;pathophysiology;personality disorder;priority journal;sickle cell trait;urinalysis;white matter;white matter lesion,"Martinez-Saez, E.;Shah, S.;Costa, C.;Fleminger, S.;Connor, S.;Bodi, I.",2012,,,0,
2654,Diagnostic value of lobar microbleeds in individuals without intracerebral hemorrhage,"Introduction The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. Methods We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. Results We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of ""probable CAA"" (≥2 strictly lobar MBs) was 87.5% (95% confidence interval [CI], 60.4-97.8) and 25% (95% CI, 13.2-78) in hospital and general populations, respectively. Discussion Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.",,"Martinez-Ramirez, S.;Romero, J. R.;Shoamanesh, A.;McKee, A. C.;Van Etten, E.;Pontes-Neto, O.;Macklin, E. A.;Ayres, A.;Auriel, E.;Himali, J. J.;Beiser, A. S.;Decarli, C.;Stein, T. D.;Alvarez, V. E.;Frosch, M. P.;Rosand, J.;Greenberg, S. M.;Gurol, M. E.;Seshadri, S.;Viswanathan, A.",2015,1,,0,
2655,Lipid mapping of the rat brain for models of disease,"Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K(+) and PC (32: 0)+K(+) distributed primarily in gray matter, and PC (36: 1)+K(+) and PC (38: 1)+Na(+) distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K(+) in white matter, and PA (38: 5)+K(+) in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H(+) in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H(+) in white matter. Phosphatidylserines (PS): PS (34: 1)-H(+) in gray matter, and PS (38: 1)-H(+) in white matter. Sphingomyelin (SM) SM (d18: 1/16: 0)-H(+) in ventricles and SM (d18: 1/18: 0)-H(+) in gray matter. Sulfatides (ST): ST (d18: 1/24: 1)-H(+) in white matter. The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer's disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba.","0 (Lipids);0 (Phosphatidic Acids);0 (Phosphatidylcholines);0 (Phosphatidylserines);0 (Sphingomyelins);Animals;Brain Chemistry;Disease Models, Animal;Lipids/ analysis;Male;Mass Spectrometry;Neurodegenerative Diseases/metabolism;Phosphatidic Acids/analysis;Phosphatidylcholines/analysis;Phosphatidylserines/analysis;Rats;Rats, Sprague-Dawley;Sphingomyelins/analysis;Alzheimer's disease;Brain;Imaging mass spectrometry;Phospholipid;Rat;cholinergic lesion","Martinez-Gardeazabal, J.;Gonzalez de San Roman, E.;Moreno-Rodriguez, M.;Llorente-Ovejero, A.;Manuel, I.;Rodriguez-Puertas, R.",2017,Sep,,0,2656
2656,Lipid mapping of the rat brain for models of disease,"Lipids not only constitute the primary component of cellular membranes and contribute to metabolism but also serve as intracellular signaling molecules and bind to specific membrane receptors to control cell proliferation, growth and convey neuroprotection. Over the last several decades, the development of new analytical techniques, such as imaging mass spectrometry (IMS), has contributed to our understanding of their involvement in physiological and pathological conditions. IMS allows researchers to obtain a wide range of information about the spatial distribution and abundance of the different lipid molecules that is crucial to understand brain functions. The primary aim of this study was to map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment. The results were obtained using a LTQ-Orbitrap XL mass spectrometer in positive and negative ionization modes and analyzed by ImageQuest and MSIReader software. A total of 176 different molecules were recorded based on the specific localization of their intensities. However, only 34 lipid species in negative mode and 51 in positive were assigned to known molecules with an error of 5ppm. These molecules were grouped by different lipid families, resulting in: Phosphatidylcholines (PC): PC (34: 1)+K+ and PC (32: 0)+K+ distributed primarily in gray matter, and PC (36: 1)+K+ and PC (38: 1)+Na+ distributed in white matter. Phosphatidic acid (PA): PA (38: 3)+K+ in white matter, and PA (38: 5)+K+ in gray matter and brain ventricles. Phosphoinositol (PI): PI (18: 0/20: 4)-H+ in gray matter, and PI (O-30: 1) or PI (P-30: 0)-H+ in white matter. Phosphatidylserines (PS): PS (34: 1)-H+ in gray matter, and PS (38: 1)-H+ in white matter. Sphingomyelin (SM) SM (d18: 1/16: 0)-H+ in ventricles and SM (d18: 1/18: 0)-H+ in gray matter. Sulfatides (ST): ST (d18: 1/24: 1)-H+ in white matter. The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer's disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo Escriba-Ruiz.",Alzheimer's disease;Brain;Imaging mass spectrometry;Phospholipid;Rat;cholinergic lesion,"Martinez-Gardeazabal, J.;Gonzalez de San Roman, E.;Moreno-Rodriguez, M.;Llorente-Ovejero, A.;Manuel, I.;Rodriguez-Puertas, R.",2017,Feb 21,,0,
2657,Rapid improvement of a complex migrainous episode with sodium valproate in a patient with CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease of small arteries caused by mutations in the Notch3 gene. Complex migrainous episodes, such as acute confusional migraine, status migrainosus with persisting aura, and ""CADASIL coma"" have been described in patients with CADASIL. However, there are few descriptions of effective treatment of such episodes. We describe a 44-year-old male with CADASIL, who presented with sudden-onset aphasia and decreased responsiveness after prolonged, severe migraine attack. Subsequently, the patient had two generalized seizures. A subtle status epilepticus was suspected because of drowsiness and seizures, and intravenous sodium valproate medication was initiated. EEG recording showed left hemispheric attenuation but no spike discharges, thus not confirming epileptic mechanism. The clinical status of the patient improved markedly after the initiation of valproate. The patient started speaking again; drowsiness and headache subsided. In repeated EEG recording, the left hemispheric attenuation disappeared. Diffusion weighted MR imaging showed no signs of recent ischemic events. The patient recovered fully from the episode with no further seizures. We suggest that CADASIL patients with acute complex migrainous episodes may benefit from intravenous sodium valproate. © The Author(s) 2011.",,"Martikainen, M. H.;Roine, S.",2012,January,,0,
2658,Blood pressure variability and leukoaraiosis amount in cerebral small-vessel disease,"OBJECTIVES: To analyze the correlation between blood pressure (BP) variability and leukoaraiosis (LA) amount in patients with symptomatic cerebral small-vessel disease. MATERIALS AND METHODS: We included 25 hypertensive patients: 13 with Binswanger's disease (BD) and 12 with a first-ever lacunar infarction (LI). Baseline office BP was obtained for 3 consecutive weeks. From a 24-h ambulatory BP monitoring performed 1 week later we obtained average systolic (SBP) and diastolic (DBP) BP for daytime, nighttime and 24-h periods. SBP and DBP variability was defined as the within-subject standard deviation of all readings. A standardized cerebral MR was performed in each patient and an LA score was calculated. RESULTS: No statistically significant correlation was obtained between the LA score and any of the following BP values: 1) Baseline SBP and DBP; 2) 24-h, daytime or nighttime SBP and DBP, and 3) 24-h, daytime or nighttime SBP and DBP variability. CONCLUSION: Increased BP variability is not associated with greater amounts of leukoaraiosis.","Aged;Blood Pressure Monitoring, Ambulatory/methods;Brain/*blood supply/pathology;Cerebral Ventricles/pathology;Circadian Rhythm;Dementia, Vascular/*epidemiology/pathology;Female;Humans;Hypertension/diagnosis/*epidemiology;Magnetic Resonance Imaging;Male;Severity of Illness Index","Marti-Fabregas, J.;Valencia, C.;Pujol, J.;Garcia-Sanchez, C.;Roca-Cusachs, A.;Lopez-Contreras, J.;Sole, M. J.;Marti-Vilalta, J. L.",2001,Dec,,0,
2659,Fibrinogen and the amount of leukoaraiosis in patients with symptomatic small-vessel disease,"We investigated whether there is a direct correlation between plasma fibrinogen levels and the amount of leukoaraiosis (LA) in patients with symptomatic small-vessel disease. The study included 28 patients: 12 with a first-ever lacunar infarction (LI) and 16 with Binswanger's disease (BD). The mean age was 71 years (SD 8.6), and 21 were men. For each patient, we recorded demographic data, vascular risk factors and the results of blood chemistry analysis including fibrinogen (g/l), hematocrit (decimal fraction) and total serum proteins (g/l). A cerebral MR scan was performed in each patient and an LA score was obtained by an investigator blind to clinical data, using a semiquantified scale in six areas of each cerebral hemisphere (0-4 points in each area, total scoring range 0-48 points). RESULTS: The mean (SD) for the LA score was 18.9 (10.7) and for plasma fibrinogen 3.97 (1.1). Pearson's and Spearman's correlation coefficients between fibrinogen and LA score were 0.43 (p = 0.02) and 0.49 (p = 0.007), respectively. Multiple-regression analysis between groups (LI or BD) and fibrinogen versus LA score showed the strongest association for the BD group (p = 0.014) and a direct relation with fibrinogen (p = 0.018). No statistically significant association was found between LA score and age, sex, any vascular risk factor, hematocrit or total serum protein. CONCLUSION: There is a significant correlation between plasma fibrinogen levels and the amount of LA in patients with symptomatic cerebral small-vessel disease. This result suggests that fibrinogen may be involved in the pathophysiology of LA in these patients.","Aged;Blood Chemical Analysis;Blood Proteins;Brain Infarction/diagnosis/*physiopathology;Cross-Sectional Studies;Dementia, Vascular/diagnosis/*physiopathology;Female;Fibrinogen/*metabolism;Hematocrit;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Severity of Illness Index","Marti-Fabregas, J.;Valencia, C.;Pujol, J.;Garcia-Sanchez, C.;Marti-Vilalta, J. L.",2002,,66161,0,
2660,Brain morphology links systemic inflammation to cognitive function in midlife adults,"BACKGROUND: Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. METHODS: Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30-54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. RESULTS: Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. CONCLUSIONS: Inflammation and adiposity might relate to cognitive decline via influences on brain morphology.",Adult;Brain/*pathology;C-Reactive Protein/*metabolism;Cognition/*physiology;Executive Function;Female;Humans;Inflammation/blood/*pathology/psychology;Interleukin-6/*blood;Magnetic Resonance Imaging;Male;Middle Aged;Neuroimaging;Neuropsychological Tests;Organ Size/physiology;Brain atrophy;C-reactive protein;Cognitive aging;Cognitive decline;Gray matter volume;Inflammation;Interleukin-6,"Marsland, A. L.;Gianaros, P. J.;Kuan, D. C.;Sheu, L. K.;Krajina, K.;Manuck, S. B.",2015,Aug,10.1016/j.bbi.2015.03.015,0,
2661,White matter hyperintensities and cortical acetylcholinesterase activity in parkinsonian dementia,"OBJECTIVE: To investigate the relationship between the severity of white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity in parkinsonian dementia (PDem). METHODS: PDem (n = 11) and control subjects (n = 14) underwent [11C]methyl-4-piperidinyl propionate (11C-PMP) AChE brain positron emission tomography and magnetic resonance (MR) imaging. Presence of WMH on proton density and T2 MR images was scored using a modified version of the semi-quantitative rating scale by Scheltens et al. [J Neurol Sci114 (1993)]. RESULTS: Analysis demonstrated significantly lower mean cortical (11)C-PMP k3 hydrolysis rates in PDem (-19.9%) when compared with control subjects (P < 0.0001). PDem subjects had higher mean severity of WMH (+20.1%) when compared with control subjects (P < 0.05). When WMH severity was entered into the analysis of variance model, there was no significant co-variate effect on cortical AChE activity (F = 0.24, ns). CONCLUSIONS: The concomitant presence of mild to moderate WMH in patients with PDem does not have a significant effect on cortical AChE activity.",Acetylcholinesterase/ metabolism;Aged;Case-Control Studies;Cerebral Cortex/ enzymology/ pathology/radionuclide imaging;Dementia/ enzymology/etiology/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Parkinsonian Disorders/enzymology/pathology/ psychology;Severity of Illness Index,"Marshall, G. A.;Shchelchkov, E.;Kaufer, D. I.;Ivanco, L. S.;Bohnen, N. I.",2006,Feb,10.1111/j.1600-0404.2005.00553.x,0,
2662,Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly,"OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly. METHODS: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH. RESULTS: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005). CONCLUSIONS: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory.",Aged;Basal Ganglia/pathology;Brain/ pathology/ physiology;Cognition;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Psychological Tests,"Marshall, G. A.;Hendrickson, R.;Kaufer, D. I.;Ivanco, L. S.;Bohnen, N. I.",2006,Jan,10.1002/gps.1419,0,
2663,"Dementia, pyramidal system involvement, and leukoencephalopathy with a presenilin 1 mutation","The authors describe four members of a family with a novel P284S presenilin 1 mutation presenting a clinical phenotype characterized by early-onset dementia, paratetraparesis, dysarthria, dysphagia, and marked involvement of brain white matter. The distinctive clinical and MRI findings in the family studied extend the phenotypic spectrum of dementia associated with mutation of the PS1 gene.","Adult;Aged;Brain/*pathology/physiopathology;Brain Damage, Chronic/complications/*genetics/physiopathology;DNA Mutational Analysis;Deglutition Disorders/complications/genetics/physiopathology;Dementia/complications/*genetics/physiopathology;Dysarthria/complications/genetics/physiopathology;Family Health;Female;Genetic Testing;Humans;Magnetic Resonance Imaging;Male;Membrane Proteins/*genetics;Mutation/*genetics;Pedigree;Phenotype;Presenilin-1;Quadriplegia/complications/*genetics/physiopathology;Syndrome","Marrosu, M. G.;Floris, G.;Costa, G.;Schirru, L.;Spinicci, G.;Cherchi, M. V.;Mura, M.;Mascia, M. G.;Cocco, E.",2006,Jan 10,10.1212/01.wnl.0000191360.08881.12,0,
2664,[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging,"[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.",Alzheimer;Braak staging;Neurofibrillary tangles;Pet;Tau;[F-18]-av-1451,"Marquie, M.;Siao Tick Chong, M.;Anton-Fernandez, A.;Verwer, E. E.;Saez-Calveras, N.;Meltzer, A. C.;Ramanan, P.;Amaral, A. C.;Gonzalez, J.;Normandin, M. D.;Frosch, M. P.;Gomez-Isla, T.",2017,Oct,,0,
2665,Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies,"OBJECTIVE: Recent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases. METHODS: We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays, and quantitative tau measurements in postmortem brain samples from two progressive supranuclear palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging before death. RESULTS: The three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined, with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments. INTERPRETATION: AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies. ANN NEUROL 2017;81:117-128.",,"Marquie, M.;Normandin, M. D.;Meltzer, A. C.;Siao Tick Chong, M.;Andrea, N. V.;Anton-Fernandez, A.;Klunk, W. E.;Mathis, C. A.;Ikonomovic, M. D.;Debnath, M.;Bien, E. A.;Vanderburg, C. R.;Costantino, I.;Makaretz, S.;DeVos, S. L.;Oakley, D. H.;Gomperts, S. N.;Growdon, J. H.;Domoto-Reilly, K.;Lucente, D.;Dickerson, B. C.;Frosch, M. P.;Hyman, B. T.;Johnson, K. A.;Gomez-Isla, T.",2017,Jan,,0,
2666,Communication among neurons,"The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are considered and the relation to the prevailing beta-amyloid hypothesis is discussed.","Adolescent;Adult;Age Factors;Aged;Aged, 80 and over;Aging/pathology/ physiology;Brain/pathology/ physiology;Case-Control Studies;Confidence Intervals;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated;Neurons/ physiology;Positron-Emission Tomography;Presynaptic Terminals/physiology;Schizophrenia/pathology;Statistics as Topic;Young Adult","Marner, L.",2012,Apr,,0,
2667,Could better phenotyping small vessel disease provide new insights into Alzheimer Disease and improve clinical trial outcomes?,"Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the co-occurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design.",,"Marnane, M.;Hsiung, G. R.",2016,Feb 21,,0,
2668,Periventricular hyperintensities are associated with elevated cerebral amyloid,"Objective: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral beta-amyloid (Abeta) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. Methods: The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Abeta, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET. Results: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Abeta (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p 0.05) PVWMH were independently associated with CSF-Abeta. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Abeta levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements. Conclusions: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.",age;aged;Alzheimer disease/di [Diagnosis];article;cerebrospinal fluid analysis;controlled study;disease association;education;ethnicity;female;frontal cortex;genotype;human;major clinical study;male;mild cognitive impairment;multicenter study;nuclear magnetic resonance imaging;observational study;parietal cortex;periventricular white matter hyperintensity;positron emission tomography;priority journal;prospective study;pulse pressure;race;randomized controlled trial;risk factor;secondary prevention;sex;white matter lesion;amyloid beta protein/ec [Endogenous Compound];antihypertensive agent;antilipemic agent;antithrombocytic agent;cholinesterase inhibitor;florbetapir f 18;fluorodeoxyglucose;memantine;tau protein/ec [Endogenous Compound],"Marnane, M.;Al-Jawadi, O. O.;Mortazavi, S.;Pogorzelec, K. J.;Wang, B. W.;Feldman, H. H.;Hsiung, G. Y.",2016,,10.1212/wnl.0000000000002352,0,
2669,Diagnostic strategies in CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migraine, recurrent stroke, and dementia. It results from mutations in the notch3 gene but mutations may occur at multiple sites making molecular diagnosis time consuming. It has been suggested that the presence of granular osmiophilic material (GOM) on skin biopsy and involvement of the anterior temporal lobe and external capsule on MRI may help in diagnosis. METHODS: The authors identified 83 potential index cases from the British population and screened exons 2 to 23 of notch3. MRI scans were scored using a modified Scheltens scale. Skin biopsy was performed in a subgroup. RESULTS: Fifteen different point mutations were identified in 48 families, 73% of which were in exon 4, 8% in exon 3, and 6% in each of exons 5 and 6. Moderate or severe involvement of the anterior temporal pole on MRI had a sensitivity of 89% and specificity of 86% for diagnosis of CADASIL, whereas external capsule involvement had a high sensitivity of 93% but a low specificity of 45%. Skin biopsy, performed in 18 cases, had a sensitivity of 45% and specificity of 100%. CONCLUSIONS: The spectrum of mutations in this study can be used to plan appropriate screening protocols; a suggested protocol is to screen exon 4, and proceed to exons 3, 5, and 6 where indicated. GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker.","Adult;Aged;Biopsy/statistics & numerical data;Dementia, Multi-Infarct/*diagnosis/genetics;Female;Humans;Magnetic Resonance Imaging/statistics & numerical data;Male;Middle Aged;Point Mutation/genetics;Proto-Oncogene Proteins/genetics;*Receptors, Cell Surface;Receptors, Notch;Skin/pathology;Statistics, Nonparametric","Markus, H. S.;Martin, R. J.;Simpson, M. A.;Dong, Y. B.;Ali, N.;Crosby, A. H.;Powell, J. F.",2002,Oct 22,,0,
2670,Association between brain MRI diffusion alterations and CSF biomarkers in amnestic mci,"Background: Subjects with mild cognitive impairment (MCI) and abnormal levels of CSF Abeta42, Abeta42/t-tau and/or Abeta42/p-tau ratios are at higher risk of cognitive decline. Diffusion tensor imaging (DTI) is a quantitative MRI technique that enables the in vivo identification of white matter (WM) tissue alterations and can help in identifying early changes inmci. The goal of this study was to characterize microstructural features of amnesticmci patients with three different risk of cognitive decline, defined accordingly to their baseline CSF levels of Abeta42, Abeta/t-tau and Abeta/p-tau ratios: positive (MCI+), intermediate (MCI-int) and negative (MCI-). Methods: 147 MCI patients were enrolled across 13 centres in Europe (E-ADNI) and underwent CSF collection and multicentric 3T MRI. Fractional anisotropy (FA), mean (MD), axial (axd) and radial (RD) diffusivities in the major WM tracts were computed with atlas-based ROI analysis and confirmed with probabilistic tractography (TRACULA). Statistical analysis was performed using analysis of covariance corrected for age and gender; between groups differences (MCI+, MCI-int and MCI-) were computed with Bonferroni posthoc. Results: Both the atlas-based and probabilistic tractography analyses gave consistent results. Abeta/p-tau and Abeta42 MCI+, relative to the MCI-, showed a pathological alterations of all the diffusion metrics considered (i.e. Lower FA, higher axd, RD and MD) in the splenium of the corpus callosum (p<.05). In this region, Abeta/t-tau MCI+ reported differences only in the MD (p<.01). For all the classifications, comparison in the cingulum of the hippocampus reported a bilateral FA decrease and an increase in RD and MD, preferentially in the right hemisphere, of mci+ relative tomci-. Diffusion indices in themci-int group were generally intermediate betweenmci+ and MCI-. Conclusions: Our results suggest that i) Abeta/p-tau and Abeta classifications are more sensitive than Abeta/t-tau classification in detecting white matter micro structural alterations in amnesticmci patients, ii) splenium and cingulum of the hippocampus are affected at early stages in the disease.",analysis of covariance;cingulum (brain);classification;clinical trial;controlled clinical trial;controlled study;corpus callosum;diencephalon;diffusion;Europe;female;fractional anisotropy;gender;hippocampus;human;major clinical study;male;mild cognitive impairment;multicenter study;nuclear magnetic resonance imaging;right hemisphere;tractography;white matter;amyloid beta-protein (1-42),"Marizzoni, M.;Pievani, M.;Pini, L.;Jovicich, J.;Nobili, F.;Ranjeva, J. P.;Bartres-Faz, D.",2017,,,0,
2671,Meta-analysis of epigenome-wide association studies of cognitive abilities,"Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P < 1.7 x 10(-8)) associations for global cognitive function (cg21450381, P = 1.6 x 10(-8)), and phonemic verbal fluency (cg12507869, P = 2.5 x 10(-9)). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 x 10(-5) and 4 x 10(-13) in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.",,"Marioni, R. E.;McRae, A. F.;Bressler, J.;Colicino, E.;Hannon, E.;Li, S.;Prada, D.;Smith, J. A.;Trevisi, L.;Tsai, P. C.;Vojinovic, D.;Simino, J.;Levy, D.;Liu, C.;Mendelson, M.;Satizabal, C. L.;Yang, Q.;Jhun, M. A.;Kardia, S. L. R.;Zhao, W.;Bandinelli, S.;Ferrucci, L.;Hernandez, D. G.;Singleton, A. B.;Harris, S. E.;Starr, J. M.;Kiel, D. P.;McLean, R. R.;Just, A. C.;Schwartz, J.;Spiro, A., 3rd;Vokonas, P.;Amin, N.;Ikram, M. A.;Uitterlinden, A. G.;van Meurs, J. B. J.;Spector, T. D.;Steves, C.;Baccarelli, A. A.;Bell, J. T.;van Duijn, C. M.;Fornage, M.;Hsu, Y. H.;Mill, J.;Mosley, T. H.;Seshadri, S.;Deary, I. J.",2018,Jan 8,,0,
2672,"Clinical, neurovascular and neuropathological features in Sneddon's syndrome","Sneddon's syndrome (SS) is characterized by ischemic cerebrovascular episodes and livedo reticularis. It is more common in young women and can also be associated with valvulopathy, a history of spontaneous abortion, renal involvement and vascular dementia. We describe three cases of young women with this disease. The patients had repeated ischemic cerebral episodes, livedo reticularis and thrombocytopenia. CT and MRI showed strokes and cerebral atrophy. Autopsy in one of the patients revealed cerebral infarctions. Anticardiolipin antibodies were detected in two patients. Antiphospholipid antibodies may be found in some patients with ischemic cerebrovascular events and livedo reticularis. SS may thus be associated with antiphospholipid syndrome. We described three new cases of SS and discuss the pathophysiology of this disease.",anticoagulant agent;cardiolipin antibody;heparin;phospholipid antibody;adult;antiphospholipid syndrome;article;autopsy;brain atrophy;brain infarction;case report;cerebrovascular accident;clinical feature;computer assisted tomography;disease association;female;high risk population;human;kidney disease;livedo reticularis;mitral valve disease;multiinfarct dementia;neuroimaging;neuropathology;nuclear magnetic resonance imaging;pathophysiology;Sneddon syndrome;spontaneous abortion;thrombocytopenia,"Marinho, J. L.;Piovesan, É J.;Neto, M. P. L.;Kotze, L. R.;De Noronha, L.;Twardowschy, C. A.;Lange, M. C.;Scola, R. H.;Flumignan Zétola, V. H.;Nóvak, E. M.;Werneck, L. C.",2007,,,0,
2673,Vascular risk factors in mild cognitive impairment subtypes: Findings from the ReGAl project,"Background and Aim: To investigate the role of vascular risk factors in different subtypes of mild cognitive impairment (MCI) in a multicentric, clinic-based, cross-sectional study. Methods: Two-hundred and seven subjects with MCI were included in the study: 33 with single non-memory MCI (snmMCI), 42 with multiple-domain amnestic MCI (mdMCI-a) and 132 with amnestic MCI (aMCI). Several clinical vascular risk factors and magnetic resonance imaging (MRI) brain lesions were evaluated. Results: snmMCI showed a higher frequency of ischaemic heart disease and of transient ischaemic attack (TIA)/stroke, a higher Hachinski ischaemic score and a higher frequency of white-matter lesions on MRI compared to aMCI. Subjects with mdMCI-a showed clinical characteristics similar to aMCI, except for a higher frequency of a history of TIA/stroke. Conclusion: Our findings suggest that snmMCI may be considered a vascular cognitive disorder. Copyright © 2007 S. Karger AG.",,"Mariani, E.;Monastero, R.;Ercolani, S.;Mangialasche, F.;Caputo, M.;Feliziani, F. T.;Vitale, D. F.;Senin, U.;Mecocci, P.",2007,November,,0,
2674,Single strategic infarct dementia mimicking dementia with lewy bodies,,aged;brain ischemia;case report;cognitive defect;dementia;Doppler flowmetry;electrocardiography;female;human;hypertension;laboratory test;letter;Lewy body;Mini Mental State Examination;nuclear magnetic resonance imaging;single strategic infarct dementia;transthoracic echocardiography;visual hallucination,"Marianetti, M.;Izzo, C.;Fratino, M.;Mina, C.",2010,,,0,
2675,The course of Binswanger's disease as chronicled over a period of seven years,"An autopsy-confirmed case of dementia due to Binswanger's disease is presented in detail. A concurrent diary of the course of disease in this individual over the last 10 years of her life was available, making it possible to reconstruct the case as it developed over a seven-year period. Binswanger's disease is a subset of vascular dementia, with major involvement of the subcortical white matter nourished by terminal arterioles. The diagnosis is difficult during life because of the clinical overlap with dementing diseases of other causes. The downhill course in this case was quite rapid, and some of the manifestations were clearly those of subcortical involvement, notable in the observations by the family and corroborated by the imaging study of the brain.",,"Margolin, E. G.;Balko, M. G.",2001,2001,,0,
2676,Baseline and longitudinal increases in diastolic blood pressure are associated with greater white matter hyperintensity volume: the northern Manhattan study,"BACKGROUND AND PURPOSE: Elevated blood pressure (BP) is a risk factor for stroke and dementia, but the effect of BP, and change in BP over time, on white matter hyperintensity volume (WMHV) is not fully understood. Few studies have included Hispanics, who are at greater risk of stroke and dementia than non-Hispanic whites. We examined BP in relation to WMHV in a stroke-free cohort. METHODS: The Northern Manhattan Study includes 1290 stroke-free participants who had brain MRI. We examined baseline systolic and diastolic (DBP) BP, and changes in BP from baseline to MRI, and WMHV. RESULTS: There were 1281 participants with brain MRI and 2 BP measurements (mean age, 64 years; SD=8; range, 40 to 94 years). Baseline DBP was associated with greater WMHV (P<0.0001) independent of sociodemographic and vascular risk factors. Each 10 mm Hg above the mean baseline DBP (83±11 mm Hg) was associated with a 1.17% greater WMHV. Over 7 years average follow-up, participants with an increase >5 mm Hg DBP from baseline to MRI had 1.21% greater WMHV relative to those whose BP did not increase (P=0.02). The association between baseline DBP and WMHV was strongest for blacks compared with Hispanics and whites (interaction P=0.04). CONCLUSIONS: Baseline DBP and longitudinal increases in DBP were independently associated with a greater WMHV, and the association between DBP and WMHV was greatest among blacks.","African Americans;Blood Pressure;Cerebellum [physiopathology] [radiography];Dementia, Vascular [etiology] [physiopathology] [radiography];European Continental Ancestry Group;Follow-Up Studies;Hispanic Americans;Magnetic Resonance Imaging;Stroke [ethnology] [etiology] [physiopathology] [radiography];Adult[checkword];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-htn","Marcus, J.;Gardener, H.;Rundek, T.;Elkind, M. S.;Sacco, R. L.;Decarli, C.;Wright, C. B.",2011,,10.1161/strokeaha.111.617571,0,
2677,White matter disruption and connected speech in non-fluent and semantic variants of primary progressive aphasia,"Differential patterns of white matter disruption have recently been reported in the non-fluent (nfvPPA) and semantic (svPPA) variants of primary progressive aphasia (PPA). No single measure is sufficient to distinguish between the PPA variants, but connected speech allows for the quantification of multiple measures. The aim of the present study was to further investigate the white matter correlates associated with connected speech features in PPA. We examined the relationship between white matter metrics and connected speech deficits using an automated analysis of transcriptions of connected speech and diffusion tensor imaging in language-related tracts. Syntactic, lexical, and semantic features were automatically extracted from transcriptions of topic-directed interviews conducted with groups of individuals with nfvPPA or svPPA as well as with a group of healthy controls. A principal component analysis was performed in order to reduce the number of language measures and yielded a five-factor solution. The results indicated that nfvPPA patients differed from healthy controls on a syntactic factor, and svPPA patients differed from controls on two semantic factors. However, the patient groups did not differ on any factor. Moreover, a correlational analysis revealed that the lexical richness factor was significantly correlated with radial diffusivity in the left inferior longitudinal fasciculus, which suggests that semantic deficits in connected speech reflect a disruption of this ventral pathway, and which is largely consistent with the results of previous studies. Using an automated approach for the analysis of connected speech combined with probabilistic tractography, the present findings demonstrate that nfvPPA patients are impaired relative to healthy controls on syntactic measures and have increased radial diffusivity in the left superior longitudinal fasciculus, whereas the svPPA group was impaired on lexico-semantic measures relative to controls and showed increased radial diffusivity in the uncinate and inferior longitudinal fasciculus bilaterally.",aged;article;automation;clinical article;connected speech;controlled study;diffusion tensor imaging;female;genetic variability;human;inferior longitudinal fasciculus;interview;language;male;neuroimaging;non fluent variant primary progressive aphasia;primary progressive aphasia;priority journal;semantic variant primary progressive aphasia;semantics;speech;superior longitudinal fasciculus;tractography;white matter;white matter disruption,"Marcotte, K.;Graham, N. L.;Fraser, K. C.;Meltzer, J. A.;Tang-Wai, D. F.;Chow, T. W.;Freedman, M.;Leonard, C.;Black, S. E.;Rochon, E.",2017,,10.1159/000456710,0,
2678,Effects of high-frequence transcranial magnetic stimulation on cognition of elderly with cognitive impairment no-dementia (CIND),"Objective: To verify the effects of high-frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) on global cognition of functionally independent elderly with subjective complaints of memory decline. Methods: Clinical trial. Nineteen (8 male and 11 female) elderly, aged between 60 and 74 years old (mean age=64.5+/-3.8), independent for instrumental activities of daily living (IADL) with subjective memory complaints and evidence of some impairment in neuropsychological assessment, characterizing cognitive impairment no-dementia (CIND). The MoCA test was used for screening. For each patient, a brain magnetic resonance image excluded major causes of cerebrovascular disease and white matter lesions, evidence of focal atrophy or lacunes. Subjects were randomized into two groups: (I) active rTMS (n=9) and (II) sham rTMS (n=10). A rapid magnetic stimulator and a figure-of-eight cooled coil was used. We delivered 10 sessions of high-frequence rTMS (10 Hz) for 5 seconds to the left DLPFC, with the parameters: 50 stimuli/train, 40 trains, 25 seconds of intertrain interval, 2.000 pulses/session and intensity of 110% of motor threshold. The placebo group used a sham coil. Follow-up (""off-line"" paradigm) was obtained by detailed neuropsychological assessment encompassing all cognitive domains including the Rivermead Memory Behavioural Test (RMBT) and Stroop. Testing was applied at baseline, after rTMS and one month later. All participants gave written informed consent. Results: These preliminary results showed improvement higher than 10% in the performance of RMBT and Stroop tests (ANOVA, p=0.028 and p=0.038, respectively) after rTMS sessions. The improvement was sustained after one month on RMBT scores, but not on STROOP test. (Updated results will be showed on the poster presentation). Conclusion: Although sample size is still statistically limiting, the results suggest cognitive response in memory and attention to highfrequency rTMS, and a sustained effect in memory after one month.",transcranial magnetic stimulation;cognition;aged;human;cognitive defect;dementia;psychopharmacology;memory;Stroop test;male;follow up;atrophy;white matter lesion;cerebrovascular disease;clinical trial;nuclear magnetic resonance;brain;sample size;patient;prefrontal cortex;screening;parameters;informed consent;daily life activity;female;placebo,"Marcolin, M. A.;Drumond Marra, H. L.;Myckowski, M. L.;Memoria, C. M.;Arnaut, D.;Forlenza, O. V.",2012,,10.1017/s1461145712000508,0,
2679,Cerebral scedosporiosis: An emerging fungal infection in severe neutropenic patients: CT features and CT pathologic correlation,"Scedosporium prolificans is an emerging opportunistic fungal agent encountered in severely neutropenic patients. The purpose of this paper is to describe the main cranial CT findings from a retrospective review of six patients (four men and two women, 18-66 years old) afflicted with disseminated infection by S. prolificans with neurological symptoms. They were severely neutropenic and presented with severe respiratory failure and conscience deterioration, with a subsequent 100% mortality. The final diagnosis was established by autopsy (performed in five patients) and blood culture findings. Cranial CT showed multiple low-density lesions in four patients without contrast enhancement located in the basal ganglia and corticomedullary junction. Autopsy findings of these lesions demonstrated necrosis and hyphae proliferation inside brain infarcts. Also, two of the patients had a subarachnoid hemorrhage, but angiography could not be performed. CT and autopsy findings were fairly similar to those encountered in cerebral aspergillosis; however, possibly because of its rapid and fatal evolution, no edema or ring enhancing lesions were encountered. Thus, Scedosporium can be included as a rare but possible cause of invasive fungal disseminated central nervous system infections in severely neutropenic patients. © Springer-Verlag 2005.",amphotericin B;fluconazole;immunosuppressive agent;itraconazole;acute myeloblastic leukemia;adult;aged;article;aspergillosis;autopsy;basal ganglion;blood culture;brain angiography;brain damage;brain edema;brain infection;brain necrosis;cerebral scedosporiosis;clinical article;computer assisted tomography;contrast enhancement;disease severity;female;fungus growth;fungus hyphae;human;male;medulla oblongata;mental deterioration;mortality;mycosis;myelodysplastic syndrome;myeloma;neurologic disease;neutropenia;pathogenesis;priority journal;respiratory failure;Scedosporium;Lomentospora prolificans,"Marco de Lucas, E.;Sádaba, P.;Lastra García-Barón, P.;Ruiz Delgado, M. L.;Cuevas, J.;Salesa, R.;Bermúdez, A.;González Mandly, A.;Gutiérrez, A.;Fernández, F.;Marco de Lucas, F.;Díez, C.",2006,,,0,
2680,The aging brain and cognition: contribution of vascular injury and abeta to mild cognitive dysfunction,"IMPORTANCE: beta-Amyloid (Abeta) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD). OBJECTIVE: To examine the relationship between neuroimaging measures of VBI and brain Abeta deposition and their associations with cognition. DESIGN AND SETTING: A cross-sectional study in a community- and clinic-based sample recruited for elevated vascular disease risk factors. PARTICIPANTS: Clinically normal (mean age, 77.1 years [N = 30]), cognitively impaired (mean age, 78.0 years [N = 24]), and mildly demented (mean age, 79.8 years [N = 7]) participants. INTERVENTIONS: Magnetic resonance imaging, Abeta (Pittsburgh Compound B-positron emission tomographic [PiB-PET]) imaging, and cognitive testing. MAIN OUTCOME MEASURES: Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Abeta deposition; PiB positivity (29 PiB-positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory. RESULTS: Vascular brain injury and Abeta were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P < .05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. CONCLUSIONS AND RELEVANCE: In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Abeta in contemporaneous cognitive function and remained predictive after including the possible influence of Abeta. There was no evidence that VBI increases the likelihood of Abeta deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment.","Aged;Aged, 80 and over;Aging/*pathology;Amyloid beta-Peptides/*metabolism;Aniline Compounds;Apolipoproteins E/genetics;Brain Infarction/etiology;Cross-Sectional Studies;Executive Function;Female;Humans;Magnetic Resonance Imaging;Male;Memory;Mental Status Schedule;Mild Cognitive Impairment/*etiology/genetics/*pathology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography;Thiazoles;Vascular System Injuries/*complications","Marchant, N. L.;Reed, B. R.;Sanossian, N.;Madison, C. M.;Kriger, S.;Dhada, R.;Mack, W. J.;DeCarli, C.;Weiner, M. W.;Mungas, D. M.;Chui, H. C.;Jagust, W. J.",2013,Apr,10.1001/2013.jamaneurol.405,0,
2681,The aging brain and cognition: Contribution of vascular injury and Aβ to mild cognitive dysfunction,"Importance: β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD). Objective: To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition. Design and Setting: A cross-sectional study in a communityand clinic-based sample recruited for elevated vascular disease risk factors. Participants: Clinically normal (mean age, 77.1 years [N=30]), cognitively impaired (mean age, 78.0 years [N=24]), and mildly demented (mean age, 79.8 years [N=7]) participants. Interventions: Magnetic resonance imaging, Aβ (Pittsburgh Compound B-positron emission tomographic [PiBPET]) imaging, and cognitive testing. Main Outcome Measures: Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory. Results: Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P<.05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. Conclusions and Relevance: In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Aβ in contemporaneous cognitive function and remained predictive after including the possible influence of Aβ. There was no evidence that VBI increases the likelihood of Aβ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment. © 2013 American Medical Association. All rights reserved.",,"Marchant, N. L.;Reed, B. R.;Sanossian, N.;Madison, C. M.;Kriger, S.;Dhada, R.;Mack, W. J.;De Carli, C.;Weiner, M. W.;Mungas, D. M.;Chui, H. C.;Jagust, W. J.",2013,April,,0,
2682,"Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging","Using high-resolution positron emission tomography and the oxygen 15 continuous inhalation method, we examined the changes in cerebral metabolic rate of oxygen, blood flow, blood volume, and oxygen extraction fraction as a function of age in 25 optimally healthy, unmedicated volunteers who ranged in age from 20 to 68 years. Subjects were strictly selected for absence of cerebrovascular risk factors, dementia, or mental disorders; they had neither biological nor clinical abnormalities, and no focal anomaly on computed tomographic scan. Regions of interest were determined according to the anatomical structures defined on corresponding computed tomographic scan cuts obtained using a stereotaxic head-positioning method. This same method was also used for positron emission tomographic imaging. There was no significant effect of aging on PaCO2 values, hematocrit, arterial blood pressure, cholesterol and triglyceride levels, and blood glucose levels. In most cerebral cortex gyri, the cerebral metabolic rate of oxygen significantly decreased with age according to a linear pattern, with the same magnitude (about -6% per decade) in all four lobes and on both sides. This effect of age on cortical cerebral metabolic rate of oxygen persisted when the possible influence of cortical atrophy, gender, and head size were partialled out. In contrast, the white matter, deep gray nuclei, thalamus, and cerebellum were not significantly affected. The cerebral blood volume declined with a similar pattern to cerebral metabolic rate of oxygen, while changes in cerebral blood flow were less significant, presumably because of larger variance of data across subjects.(ABSTRACT TRUNCATED AT 250 WORDS)",Adult;Aged;Aging/metabolism/ physiology;Blood Volume;Brain/ physiology/radionuclide imaging;Cerebrovascular Circulation;Female;Humans;Male;Middle Aged;Oxygen Consumption,"Marchal, G.;Rioux, P.;Petit-Taboue, M. C.;Sette, G.;Travere, J. M.;Le Poec, C.;Courtheoux, P.;Derlon, J. M.;Baron, J. C.",1992,Oct,,0,
2683,Study of followup CT scans from stroke to vascular dementia,"Objective: To study the pathogenesis of vascular dementia. Methods: Followup CT scans and IQ measurement in 167 first stroke patients had been performed for five years. All patients were devided into two groups-VD group which included 95 cases who evolved vascular dementia (VD) and control group which included 72 stroke patients without dementia. The side, location, volume and amount changes of the lesions, the area of the white matter lesions (leuco-araiosis) and the quantitative indexes of cerebral atrophy between the two groups were compared. Results: 56.89% of the patients evolved dementia and 50.17% of them occurred in two years after first onset. More lesions and larger volumes especially in subcortical lesions were observed in VD group. Most of the VD patients with unilateral lesions were changed to bilateral lesions. Subcortical cerebral atrophy was more serious in VD group. There was not significant difference statistically on leuco-araiosis area changes between the two groups. Conclusion: Vascular dementia after stroke occurs largely in two years after the first onset. The occurrence of VD correlates with the relapse of stroke, the lesion volume, amount and location changes from unilateral to bilateral or left lesion enlargement. Rapid subcortical cerebral atrophy is the secondary factor of VD development. Leuco-araiosis seems to be not related to it. The effective treatment of stroke in two years after the first onset will be conducive to reduce the occurrence of VD.",article;brain atrophy;brain cortex lesion;brain size;clinical feature;computer assisted tomography;controlled study;follow up;human;intelligence quotient;major clinical study;multiinfarct dementia;quantitative analysis;statistical analysis;cerebrovascular accident;white matter,"Mao, S.;Ye, X.;Tang, Z.",2002,,,0,
2684,Parkinsonism associated with autosomal dominant bilateral striopallidodentate calcinosis,"Bilateral striopallidodentate calcinosis (BSPDC, also known as Fahr's disease, a misnomer), is a rare disorder where bilateral, almost symmetric, calcium and other mineral deposits occur in subcortical nuclei and white matter. Neurological manifestations vary but movement disorders are the most common. Of the movement disorders, parkinsonism predominates. We describe 6 patients with BSPDC associated with parkinsonism. Of the 6 patients, one patient from an autosomal dominantly inherited family who responded to levodopa, showed Lewy bodies in substantia nigra neurons and changes consistent with BSPDC. Another patient, from the same family with clinical evidence of parkinsonism and radiological and neuropathological evidence of BSPDC, did not show Lewy bodies. Ten patients with BSPDC and parkinsonism (without evidence of parathyroid dysfunction) were found in the literature. When parkinsonism is associated with dementia and cerebellar signs, obtaining a CT scan may be helpful as BSPDC often presents with the above three conditions.",,"Manyam, B. V.;Walters, A. S.;Keller, I. A.;Ghobrial, M.",2001,Oct,,0,
2685,A case of intravascular large B cell lymphoma: New clinical and immunohistochemical findings,"Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non-Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the CNS and the skin. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist of neurological and cognitive impairment, fever of unknown origin and cutaneous lesions, lacking of a typical neuroimaging pattern. For all these reasons the diagnosis is commonly missed and the exitus is frequent, therefore post mortem evaluation is necessary to clarify the clinical history. We present a case of IVLBCL in a 62-year-old woman with unusual symptomatology, mimicking a vascular, multi-infarctual cerebropathy. Hachinski Ischemic Score was 7 suggesting a vascular dementia. Autopsy was unable to define the nature of the disease. Immunohistochemical analysis for cluster of differentiation 20 (CD20) revealed the ubiquitous presence of malignant lymphoid B-cells into the vessel of all organs analyzed, allowing the definitive diagnosis of IVLBCL. The atypical cells expressed high levels of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Galectin-3, and showed cellular myelocytomatosis (c-Myc) staining in <50% of tumor nuclei. Conversely, cells were immunonegative for multiple myeloma-1 (MUM1), CD3, CD44, CD30, CD34 and CD133. Fluorescent in situ hybridization analysis for MYC rearrangements was negative. The high expression of Galectin-3 provides new insights in the understanding of molecular pathogenesis of IVLBCL; indeed, such a finding represents a prognostic factor for other types of lymphoma and should, in the same way, be taken into account in IVLBCL.",CD20 antigen;galectin 3;protein bcl 2;adult;article;ataxic gait;B lymphocyte;brain cortex;case report;clinical feature;dementia;female;fluorescence in situ hybridization;gene rearrangement;glia cell;heart failure;human;hypertension;hypoxia;immunofluorescence test;immunohistochemistry;immunoreactivity;ischemia;large cell lymphoma;lymphoid cell;mental deterioration;middle aged;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;oncogene c myc;paresthesia;priority journal;pyrexia idiopathica;white matter,"Mansueto, G.;Di Vito, A.;Belluomo, C.;Murino, P.;Natella, V.;Camastra, C.;Presta, I.;Malara, N.;de Rosa, G.;Donato, G.;Mignogna, C.",2016,,10.1111/neup.12300,0,
2686,The topographic distribution of brain atrophy in frontal lobe dementia,"The topographic distribution of brain atrophy was quantified by image analysis of fixed brain slices from ten patients dying with dementia of frontal type (DFT) and from six other patients dying with dementia of frontal type with motor neurone disease (DFT + MND). In both groups the atrophy was maximal within frontal, anterior temporal and anterior parietal regions of cortex, although other structures such as the amygdala, caudate nucleus, thalamus and hippocampus were also affected. The magnitude of the atrophy was much greater, in all affected regions, in DFT alone than in DFT + MND. Grey and white matter were affected equally in DFT alone although in DFT + MND a preferential white matter involvement was noted. No differences in the topographic distribution of the atrophy was observed in cases of DFT showing a spongiform degeneration of the cortex compared to those showing a gliotic degeneration with, or without, Pick cells and Pick bodies.",,"Mann, D. M. A.;South, P. W.",1993,1993,,0,
2687,The topographic distribution of brain atrophy in Huntington's disease and progressive supranuclear palsy,"The topographic distribution of brain atrophy was quantified by image analysis of fixed coronal brain slices from 12 patients dying with Huntington's disease (HD) and from 4 other patients dying with progressive supranuclear palsy (PSP). In HD, atrophy was maximal within the caudate nucleus, putamen and globus pallidus. However, the cerebral cortex was also atrophied with reductions in cross-sectional area within frontal, temporal and parietal lobes. In general, more white matter than grey matter was lost leading to an elevation in the grey/white matter ratio. The amygdala and thalamus were reduced in area. In PSP, lesser reductions in cortical area than those of HD were seen, these again being mostly due to a loss of white matter, resulting in an elevation of the grey/white ratio. The globus pallidus and thalamus were decreased in area, but no changes in the caudate nucleus and putamen were measured.",,"Mann, D. M. A.;Oliver, R.;Snowden, J. S.",1993,1993,,0,
2688,The topographic distribution of brain atrophy in Alzheimer's disease,"The extent of regional atrophy in ten patients, aged 52-74 years, dying with Alzheimer's disease uncomplicated pathologically by the effects of advanced old age or cerebrovascular disease, was quantified by image analysis of fixed coronal brain slices. Atrophy of the cerebral cortex was globally distributed, although the temporal lobe was most severely affected. Grey and white matter was in general affected equally. Atrophy was also present within the basal ganglia, particularly the caudate nucleus and putamen. Cerebral cortical atrophy is probably due mostly to neurofibrillary degeneration and loss of intrinsic pyramidal cells and their processes (grey matter) and axons (white matter) although loss of ascending subcortical fibres from regions such as nucleus basalis and locus caeruleus will contribute. Atrophy of the basal ganglia may relate to loss of descending cortical projections.",Aged;Alzheimer Disease/ pathology;Amyloid beta-Peptides/metabolism;Atrophy/pathology;Brain/ pathology;Brain Chemistry;Cerebral Cortex/pathology;Female;Histocytochemistry;Humans;Male;Middle Aged;Neurites/physiology;Neurofibrillary Tangles/pathology,"Mann, D. M.",1991,,,0,
2689,White matter hyperintensities and normal-appearing white matter integrity in the aging brain,"White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the invivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747× 10(-9)m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe.",,"Maniega, S. M.;Valdés Hernández, M. C.;Clayden, J. D.;Royle, N. A.;Murray, C.;Morris, Z.;Aribisala, B. S.;Gow, A. J.;Starr, J. M.;Bastin, M. E.;Deary, I. J.;Wardlaw, J. M.",2015,1,,0,
2690,Ischemia and cerebral aging. Neuro-imaging,"The incidence and prevalence of stroke increase with age. 75% of patients with stroke are over 65 year-old and the mortality rate increases with age. After the age of 55, ischemic stroke are 5 times more frequent than hemorrhagic stroke. Nevertheless ischemic stroke in aging patients presents similarly as ischemic stroke in adults. Although some ischemic lesions are more specific of aging, such as brain lacunes and vascular dementias. Neuroimaging (CT scan and MRI) plays an important role in clinical practice to help diagnose stroke, although its possibilities are limited. The situation is even more complex in aging patients in whom 'physiologic' modifications occur (brain 'atrophy' ventricular enlargment, white matter changes...). Examples of stroke and brain aging are presented and discussed, including transient ischemic attacks, lacunae, junctional infarcts, cerebral amyloid angiopathy, leuko-araiosis, and vascular dementias.",,"Manelfe, C.;Berry, I.;Arrue, P.",1994,1994,,0,
2691,Cerebral amyloid angiopathy with granulomatous angiitis ameliorated by steroid-cytoxan treatment,"We report a case of a 62-year-old black woman who, 8 months prior to death, developed confusion, apraxias, disorientation, and difficulties with her vision. There was no dementia. Computed tomography (CT) scan and magnetic resonance imaging (MRI) suggested a tumor in the right posterior parietal white matter. A biopsy of the lesion displayed granulomatous angiitis and severe cerebrovascular amyloidosis, but no tumor was identified. Chronic inflammation with an occasional multinucleated giant cell was seen about the amyloid-infiltrated vessels. The cortex demonstrated gliosis but no plaques or tangles. Subsequently, the patient was treated with steroids and Cytoxan, with an improvement in her neurologic status. She died of opportunistic broncho-pneumonia 8 months after the initial onset of her symptoms. On postmortem examination, the biopsied area of the brain showed atrophy with gliosis. Amyloid angiopathy was present but in much lesser degree than in the biopsy. Scant perivascular inflammatory infiltrates were seen only focally, and no giant cells were observed. The amyloid, both in the biopsy and autopsy material, was of the Alzheimer A4 type. This case suggests that steroid and cytoxan treatment ameliorated the angiitis and the amyloid angiopathy as well. The pertinent literature is discussed.",,"Mandybur, T. I.;Balko, G.",1992,1992,,0,
2692,Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia,"Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects. The syndrome-specific epicentre of the non-fluent/agrammatic variant of primary progressive aphasia was derived in a group of 10 mildly affected patients (clinical dementia rating equal to 0) using voxel-based morphometry. From this region, the inferior frontal gyrus (pars opercularis), we derived functional and structural connectivity maps in healthy controls (n = 30) using functional magnetic resonance imaging at rest and diffusion-weighted imaging tractography. Graph theory analysis was applied to derive functional network features. Atrophy progression was calculated using voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic patients. Correlation analyses were performed to compare volume changes in patients with connectivity measures of the healthy functional and structural speech/language network. The default mode network was used as a control network. From the epicentre, the healthy functional connectivity network included the left supplementary motor area and the prefrontal, inferior parietal and temporal regions, which were connected through the aslant, superior longitudinal and arcuate fasciculi. Longitudinal grey and white matter changes were found in the left language-related regions and in the right inferior frontal gyrus. Functional connectivity strength in the healthy speech/language network, but not in the default network, correlated with longitudinal grey matter changes in the non-fluent/agrammatic variant of primary progressive aphasia. Graph theoretical analysis of the speech/language network showed that regions with shorter functional paths to the epicentre exhibited greater longitudinal atrophy. The network contained three modules, including a left inferior frontal gyrus/supplementary motor area, which was most strongly connected with the epicentre. The aslant tract was the white matter pathway connecting these two regions and showed the most significant correlation between fractional anisotropy and white matter longitudinal atrophy changes. This study showed that the pattern of longitudinal atrophy progression in the non-fluent/agrammatic variant of primary progressive aphasia relates to the strength of connectivity in pre-determined functional and structural large-scale speech production networks. These findings support the hypothesis that the spread of neurodegeneration occurs by following specific anatomical and functional neuronal network architectures.","Aged;Aphasia, Primary Progressive/diagnostic imaging/ pathology/ physiopathology;Atrophy/etiology/pathology;Brain/diagnostic imaging/ pathology;Cohort Studies;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Language;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Neural Pathways/diagnostic imaging/ physiology;Neuropsychological Tests;Speech Production Measurement;Statistics as Topic;connectivity;functional connectivity;longitudinal atrophy;primary progressive aphasia;tractography","Mandelli, M. L.;Vilaplana, E.;Brown, J. A.;Hubbard, H. I.;Binney, R. J.;Attygalle, S.;Santos-Santos, M. A.;Miller, Z. A.;Pakvasa, M.;Henry, M. L.;Rosen, H. J.;Henry, R. G.;Rabinovici, G. D.;Miller, B. L.;Seeley, W. W.;Gorno-Tempini, M. L.",2016,Oct,,0,2693
2693,Healthy brain connectivity predicts atrophy progression in non-fluent variant of primary progressive aphasia,"Neurodegeneration has been hypothesized to follow predetermined large-scale networks through the trans-synaptic spread of toxic proteins from a syndrome-specific epicentre. To date, no longitudinal neuroimaging study has tested this hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this study was to demonstrate that longitudinal progression of atrophy in non-fluent/agrammatic variant primary progressive aphasia spreads over time from a syndrome-specific epicentre to additional regions, based on their connectivity to the epicentre in healthy control subjects. The syndrome-specific epicentre of the non-fluent/agrammatic variant of primary progressive aphasia was derived in a group of 10 mildly affected patients (clinical dementia rating equal to 0) using voxel-based morphometry. From this region, the inferior frontal gyrus (pars opercularis), we derived functional and structural connectivity maps in healthy controls (n = 30) using functional magnetic resonance imaging at rest and diffusion-weighted imaging tractography. Graph theory analysis was applied to derive functional network features. Atrophy progression was calculated using voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic patients. Correlation analyses were performed to compare volume changes in patients with connectivity measures of the healthy functional and structural speech/language network. The default mode network was used as a control network. From the epicentre, the healthy functional connectivity network included the left supplementary motor area and the prefrontal, inferior parietal and temporal regions, which were connected through the aslant, superior longitudinal and arcuate fasciculi. Longitudinal grey and white matter changes were found in the left language-related regions and in the right inferior frontal gyrus. Functional connectivity strength in the healthy speech/language network, but not in the default network, correlated with longitudinal grey matter changes in the non-fluent/agrammatic variant of primary progressive aphasia. Graph theoretical analysis of the speech/language network showed that regions with shorter functional paths to the epicentre exhibited greater longitudinal atrophy. The network contained three modules, including a left inferior frontal gyrus/supplementary motor area, which was most strongly connected with the epicentre. The aslant tract was the white matter pathway connecting these two regions and showed the most significant correlation between fractional anisotropy and white matter longitudinal atrophy changes. This study showed that the pattern of longitudinal atrophy progression in the non-fluent/agrammatic variant of primary progressive aphasia relates to the strength of connectivity in pre-determined functional and structural large-scale speech production networks. These findings support the hypothesis that the spread of neurodegeneration occurs by following specific anatomical and functional neuronal network architectures.",connectivity;functional connectivity;longitudinal atrophy;primary progressive aphasia;tractography,"Mandelli, M. L.;Vilaplana, E.;Brown, J. A.;Hubbard, H. I.;Binney, R. J.;Attygalle, S.;Santos-Santos, M. A.;Miller, Z. A.;Pakvasa, M.;Henry, M. L.;Rosen, H. J.;Henry, R. G.;Rabinovici, G. D.;Miller, B. L.;Seeley, W. W.;Gorno-Tempini, M. L.",2016,Aug 6,10.1093/brain/aww195,0,
2694,Frontal white matter tracts sustaining speech production in primary progressive aphasia,"In primary progressive aphasia (PPA), speech and language difficulties are caused by neurodegeneration of specific brain networks. In the nonfluent/agrammatic variant (nfvPPA), motor speech and grammatical deficits are associated with atrophy in a left fronto-insular-striatal network previously implicated in speech production. In vivo dissection of the crossing white matter (WM) tracts within this ""speech production network"" is complex and has rarely been performed in health or in PPA. We hypothesized that damage to these tracts would be specific to nfvPPA and would correlate with differential aspects of the patients' fluency abilities. We prospectively studied 25 PPA and 21 healthy individuals who underwent extensive cognitive testing and 3 T MRI. Using residual bootstrap Q-ball probabilistic tractography on high angular resolution diffusion-weighted imaging (HARDI), we reconstructed pathways connecting posterior inferior frontal, inferior premotor, insula, supplementary motor area (SMA) complex, striatum, and standard ventral and dorsal language pathways. We extracted tract-specific diffusion tensor imaging (DTI) metrics to assess changes across PPA variants and perform brain-behavioral correlations. Significant WM changes in the left intrafrontal and frontostriatal pathways were found in nfvPPA, but not in the semantic or logopenic variants. Correlations between tract-specific DTI metrics with cognitive scores confirmed the specific involvement of this anterior-dorsal network in fluency and suggested a preferential role of a posterior premotor-SMA pathway in motor speech. This study shows that left WM pathways connecting the speech production network are selectively damaged in nfvPPA and suggests that different tracts within this system are involved in subcomponents of fluency. These findings emphasize the emerging role of diffusion imaging in the differential diagnosis of neurodegenerative diseases.","Aged;Analysis of Variance;Aphasia, Primary Progressive/ pathology;Atrophy;Brain Mapping;Diffusion Tensor Imaging;Female;Frontal Lobe/ pathology;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology;Speech Production Measurement","Mandelli, M. L.;Caverzasi, E.;Binney, R. J.;Henry, M. L.;Lobach, I.;Block, N.;Amirbekian, B.;Dronkers, N.;Miller, B. L.;Henry, R. G.;Gorno-Tempini, M. L.",2014,Jul 16,10.1523/jneurosci.3464-13.2014,0,
2695,Cognitive and functional impairments in ischemic stroke patients with concurrent small vessel and large artery disease,"BACKGROUND AND PURPOSE: Concurrent small vessel, intracranial and extracranial large artery disease (SLAD) is common in Asian but its impact on cognitive and functional outcomes is unclear. We aimed to evaluate the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. METHODS: Chinese ischemic stroke patients with diffuse white matter lesions (WMLs) were recruited as part of the VITATOPS Trial. They were studied with MRI and MRA of brain. Various neuropsychiatric batteries were used to assess the cognitive functions. RESULTS: Totally 97 patients with acute ischemic stroke and diffuse WMLs were included, of whom 44 (45%) had SLAD. Patients with SLAD had lower Mini Mental State Examination (MMSE) when compared with the patients without SLAD. They had more behavioral symptoms and caused more stress in caregivers as assessed by the Neuropsychiatric Inventory (NPI). Multivariate regression analysis showed SLAD contributed significantly to MMSE, NPI Patient (NPI P) and NPI Care Giver (NPI CG). Among 44 patients with SLAD, 30 (68%) had severe cognitive impairment. They were older and less educated. They had more diabetes and poorer performance in neuropsychiatric tests including Mattis Dementia Rating Scale Initiation/Perseveration subset (MDRS I/P) and Clinical Dementia Rating (CDR). They also had poorer functional outcomes as assessed by Barthel Index (BI) and Instrumental activities of daily living (IADL). CONCLUSIONS: This was the first MRA-based study to take into consideration the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. Patients with SLAD had poorer cognitive and functional outcomes when compared to patients without SLAD.",Aged;Anxiety/complications/psychology;Asian Continental Ancestry Group;Brain/pathology;Brain Ischemia/complications/pathology/*psychology;Capillaries/*pathology;Carotid Arteries/pathology;Cerebral Angiography;Cerebral Arteries/*pathology;Cerebrovascular Circulation/physiology;Cognition Disorders/*etiology/pathology;Dementia/psychology;Depression/complications/psychology;Female;Hong Kong;Humans;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Stroke/etiology/pathology/*psychology;Treatment Outcome,"Man, B. L.;Fu, Y. P.;Wong, A.;Chan, Y. Y.;Lam, W.;Hui, A. C.;Leung, W. H.;Mok, V.;Wong, K. S.",2011,Oct,10.1016/j.clineuro.2011.04.001,0,
2696,"Multiple teeth extractions in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), treated with ticlopidine",,acetylsalicylic acid;amoxicillin;hydroxyzine;paracetamol;pravastatin;propranolol;ticlopidine;trimetazidine;adult;article;CADASIL;case report;denture;disease course;female;hospitalization;human;medical literature;nuclear magnetic resonance imaging;oral surgery;periodontal disease;physical examination;tooth extraction;ultrasound;aspirin,"Maman, L.;Stieltjes, N.;Galeazzi, J. M.;Kalafat, M.;Alantar, A.",2006,,,0,
2697,Influence of comorbidities in idiopathic normal pressure hydrocephalus - research and clinical care. A report of the ISHCSF task force on comorbidities in INPH,"Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes.",,"Malm, J.;Graff-Radford, N. R.;Ishikawa, M.;Kristensen, B.;Leinonen, V.;Mori, E.;Owler, B. K.;Tullberg, M.;Williams, M. A.;Relkin, N. R.",2013,,10.1186/2045-8118-10-22,0,
2698,Neuroimaging of white matter in aging and dementia,Clinical neuroscientists have focused increasing attention on white matter connections in the brain and on the effects of aging and disease on these connections. Recent advances in magnetic resonance imaging (MRI) analysis have given researchers new tools for quantifying and visualizing white matter to better relate white matter structure and function. The goals of this article are (a) to acquaint the reader with both established and newer methods for imaging and quantifying white matter anatomy and pathology; and (b) to review recent findings on white matter pathology in aging and dementia. Computer-assisted quantification appears to offer better statistical power than visual rating scales for detecting these relationships. New MR modalities such as diffusion imaging can detect white matter abnormalities not shown with conventional acquisition sequences. These newer techniques hold promise for early detection of disease and for delineating functional connections between brain areas. © 2006 Psychology Press.,,"Malloy, P.;Correia, S.;Stebbins, G.;Laidlaw, D. H.",2007,January,,0,
2699,Cerebrovascular disorders: Cerebral microbleeds linked to increased risk of cognitive decline,,Alzheimer disease;brain hemorrhage;cerebrovascular accident;dementia;executive function;human;memory disorder;mental deterioration;note;nuclear magnetic resonance imaging;priority journal,"Malkki, H.",2016,,,0,
2700,Susac's syndrome: An immune mediated endotheliopathy laden with challenges and controversies,"Susac's syndrome is a microangiopathy of the retina, inner ear and brain manifesting as a triad of encephalopathy, hearing loss and branch retinal artery occlusion. The pathological mechanism is thought to be an immune-mediated small vessel vasculitis with some pathophysiological similarity to dermatomyositis. Awareness and early recognition of this syndrome is important as early treatment with immunosuppression can minimise cognitive, audiological and visual sequelae. We report a case of a 33-year-old woman who presented with the characteristic syndrome. She was treated with immunomodulatory therapy and remains well 2 years postpresentation with no new events.",antinuclear antibody;azathioprine;cyclophosphamide;immunoglobulin;methylprednisolone;rituximab;steroid;topiramate;valproic acid;acute demyelinating encephalomyelitis;adult;article;brain disease;brain vasculitis;branch retinal artery occlusion;CADASIL;case report;Cogan syndrome;confusion;demyelinating disease;differential diagnosis;disorientation;drowsiness;drug substitution;encephalomyelitis;female;fluorescence angiography;follow up;headache;hearing impairment;human;migraine;multiple cycle treatment;multiple sclerosis;nuclear magnetic resonance imaging;perception deafness;priority journal;pure tone audiometry;Susac syndrome;treatment outcome;white matter lesion,"Malhotra, A.;Reyneke, E.;Needham, M.",2013,,,0,
2701,Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease,"OBJECTIVE: The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD). METHODS: Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors. RESULTS: In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010). CONCLUSION: Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.","Aged;Cognitive Dysfunction/epidemiology/ physiopathology;Comorbidity;Dementia/epidemiology/ physiopathology;Female;Gait Disorders, Neurologic/epidemiology/ physiopathology;Humans;Male;Middle Aged;Parkinson Disease/epidemiology/ physiopathology;Prospective Studies;Risk Factors;United Kingdom/epidemiology;Vascular Diseases/epidemiology/ physiopathology;Parkinson's disease;cerebrovascular;diabetes;gender;phenotype","Malek, N.;Lawton, M. A.;Swallow, D. M.;Grosset, K. A.;Marrinan, S. L.;Bajaj, N.;Barker, R. A.;Burn, D. J.;Hardy, J.;Morris, H. R.;Williams, N. M.;Wood, N.;Ben-Shlomo, Y.;Grosset, D. G.;Consortium, P. RoBaND Clinical",2016,Oct,,0,
2702,Vascular disease and vascular risk factors in relation to motor features and cognition in early Parkinson's disease,"OBJECTIVE: The purpose of this study was to examine the relationship between vascular disease (and vascular risk factors), cognition and motor phenotype in Parkinson's disease (PD). METHODS: Recently diagnosed PD cases were enrolled in a multicenter prospective observational longitudinal cohort study. Montreal cognitive assessment (normal >23, mild cognitive impairment 22 to 23 or lower but without functional impairment, and dementia 21 or less with functional impairment) and Movement Disorder Society Unified PD Rating Scale part 3 (UPDRS 3) scores were analyzed in relation to a history of vascular events and risk factors. RESULTS: In 1759 PD cases, mean age 67.5 (standard deviation 9.3) years, mean disease duration 1.3 (standard deviation 0.9) years, 65.2% were men, 4.7% had a history of prior stroke or transient ischemic attack, and 12.5% had cardiac disease (angina, myocardial infarction, heart failure). In cases without a history of vascular disease, hypertension was recorded in 30.4%, high cholesterol 27.3%, obesity 20.7%, diabetes 7.2%, and cigarette smoking in 4.6%. Patients with prior stroke or transient ischemic attack were more likely to have cognitive impairment (42% vs 25%) and postural instability gait difficulty (53.5% vs 39.5%), but these findings were not significant after adjustment for age, sex, and disease duration (P = .075). The presence of more than 2 vascular risks was associated with worse UPDRS 3 motor scores (beta coefficient 4.05, 95% confidence interval 1.48, 6.61, p = .002) and with cognitive impairment (ordinal odds ratio 2.24, 95% confidence interval 1.34, 3.74, p = .002). In 842 patients (47.8%) with structural brain imaging, white matter leukoaraiosis, but not lacunar or territorial infarction, was associated with impaired cognition (p = .006) and postural instability gait difficulty (p = .010). CONCLUSION: Vascular comorbidity is significantly associated with cognitive and gait impairment in patients with early PD, which may have prognostic and treatment implications. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.",Parkinson's disease;cerebrovascular;diabetes;gender;phenotype,"Malek, N.;Lawton, M. A.;Swallow, D. M.;Grosset, K. A.;Marrinan, S. L.;Bajaj, N.;Barker, R. A.;Burn, D. J.;Hardy, J.;Morris, H. R.;Williams, N. M.;Wood, N.;Ben-Shlomo, Y.;Grosset, D. G.",2016,Jun 21,10.1002/mds.26698,0,
2703,Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described inherited disorder. The pathologic gene maps on chromosome 19. The clinical spectrum of the disease consists of recurrent strokes, migraine, transient ischemic attacks, mood changes, and dementia. We report a genetically assessed CADASIL family with atypical clinical presentations of epileptic seizures. In two asymptomatic family members there were early brain abnormalities on MRI. Our report expands the clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed disorder.",adult;aged;article;autosomal dominant disorder;brain artery;cerebrovascular disease;chromosome 19;clinical article;clinical examination;dementia;family study;female;gene mapping;human;male;migraine;nuclear magnetic resonance imaging;priority journal;seizure;cerebrovascular accident;transient ischemic attack,"Malandrini, A.;Carrera, P.;Ciacci, G.;Gonnelli, S.;Villanova, M.;Palmeri, S.;Vismara, L.;Brancolini, V.;Signorini, E.;Ferrari, M.;Guazzi, G. C.",1997,,,0,
2704,Different Patterns of Correlation between Grey and White Matter Integrity Account for Behavioral and Psychological Symptoms in Alzheimer's Disease,"Behavioral disorders and psychological symptoms (BPSD) in Alzheimer's disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: Mood (i.e., anxiety and depression; ADmood), Frontal (i.e., dishinibition and elation; ADfrontal), and Psychotic (delusions and hallucinations; ADpsychotic) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD.",Alzheimer's disease;behavioral;grey matter;magnetic resonance imaging;white matter,"Makovac, E.;Serra, L.;Spano, B.;Giulietti, G.;Torso, M.;Cercignani, M.;Caltagirone, C.;Bozzali, M.",2015,,10.3233/jad-150612,0,
2705,Relationship between small cerebral white matter lesions and cognitive function in patients with Alzheimer's disease and amnestic mild cognitive impairment,"AIM: The main purpose of the present study was to investigate the influence of small cerebral white matter lesions on cognitive functions, and its difference by clinical stage. METHODS: A total of 160 patients with Alzheimer's disease and 40 older adults with amnestic mild cognitive impairment were enrolled in the present study. The Fazekas rating scale was used for the semi-quantitative measurement of white matter lesions. Participants whose scales were more than grade 2 were excluded. Associations between the degree of small white matter lesions and cognitive functions including memory, verbal fluency, working memory, processing speed, and executive function were examined. RESULTS: We found that small white matter lesions influenced the performances of neuropsychological tests differently between Alzheimer's disease and amnestic mild cognitive impairment. Analysis of covariance showed significant effects of interaction on a test that assessed categorical verbal fluency. In the amnestic mild cognitive impairment group, small periventricular white matter hyperintensities were significantly associated with poor performances in categorical verbal fluency; whereas in the Alzheimer's disease group, such associations were not observed. Deep white matter hyperintensities did not influence any cognitive functions examined in both groups. CONCLUSIONS: The results suggested the involvement of periventricular small white matter lesions on impairment in verbal fluency, and such influence might be different depending on an individual's clinical stage.","Aged;Aged, 80 and over;Alzheimer Disease/complications/diagnosis/*physiopathology;Amnesia/complications/diagnosis/*physiopathology;Cognition/*physiology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging/*methods;Male;Memory/*physiology;Middle Aged;Mild Cognitive Impairment/complications/diagnosis/*physiopathology;Neuropsychological Tests;Outpatients;Retrospective Studies;Severity of Illness Index;White Matter/*pathology;Alzheimer's disease;cognitive function;mild cognitive impairment;verbal fluency;white matter lesions","Makino, T.;Umegaki, H.;Suzuki, Y.;Yanagawa, M.;Nonogaki, Z.;Nakashima, H.;Kuzuya, M.",2014,Oct,10.1111/ggi.12176,0,
2706,Physiological fluctuations in white matter are increased in Alzheimer's disease and correlate with neuroimaging and cognitive biomarkers,"The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the Alzheimer's Disease Neuroimaging Initiative, PFWM was compared across cohorts: cognitively healthy, mild cognitive impairment, or probable AD. Secondary regression analyses were conducted between PFWM and neuroimaging, cognitive, and cerebrospinal fluid biomarkers. There was an effect of cohort on PFWM (t = 5.08, degree of freedom [df] = 424, p < 5.7 x 10(-7)), after accounting for nuisance effects from head displacement and global signal (t > 6.16). From the neuroimaging data, PFWM was associated with glucose metabolism (t = -2.93, df = 96, p = 0.004) but not ventricular volume (p < 0.49) or hippocampal volume (p > 0.44). From the cognitive data, PFWM was associated with composite memory (t = -3.24, df = 149, p = 0.0015) but not executive function (p > 0.21). PFWM was not associated with cerebrospinal fluid biomarkers. In one final omnibus model to explain PFWM (n = 124), glucose metabolism (p = 0.04) and cohort (p = 0.008) remained significant, as were global and head motion root-mean-square terms, whereas memory was not (p = 0.64). PFWM likely reflects end-arteriole intracranial pulsatility effects that may provide additional diagnostic potential in the context of AD neurodegeneration.","0 (Biomarkers);IY9XDZ35W2 (Glucose);Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology/ physiopathology/psychology;Biomarkers/metabolism;Cognition;Cohort Studies;Female;Functional Neuroimaging;Glucose/metabolism;Humans;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Middle Aged;Regression Analysis;Rest/physiology;White Matter/ pathology/ physiopathology;Alzheimer's disease;Neurodegeneration;Physiological noise;Pulsatility;Resting-state functional MRI;White matter","Makedonov, I.;Chen, J. J.;Masellis, M.;MacIntosh, B. J.;Alzheimer's Disease Neuroimaging, Initiative",2016,Jan,,0,
2707,Cerebral small vessel disease in aging and Alzheimer's disease: a comparative study using MRI and SPECT,"BACKGROUND: White matter hyperintensities (WMH) are associated with aging and are prevalent in various brain pathologies. The purpose of the current study was to characterize WMH perfusion in age-matched elderly controls (ECs) and patients with Alzheimer's disease (ADs). METHODS: Fifty ECs (23 men) and 61 ADs (33 men) underwent magnetic resonance imaging (MRI), 99mTc-ECD single-photon emission computed tomography (SPECT) and cognitive testing. Brain tissue type was classified on T1 weighted images, and WMH were identified on interleaved proton density/T2 weighted images. Co-registered MR images were used to characterize SPECT perfusion patterns. RESULTS: WMH perfusion was lower than normal appearing white matter (NAWM) perfusion (P < 0.001) in both EC and AD groups. There was no WMH perfusion difference between groups when considering the mean perfusion from all WMH voxels (P > 0.43). However, locations that were likely to be considered WMH tended to have lower perfusion in ADs compared with ECs. Perfusion gradients along watershed white matter regions were significantly different between EC and AD groups (P < 0.05). A relationship was found between the volume of a WMH lesion and its mean perfusion (P < 0.001) in both ECs and ADs. CONCLUSION: Global WMH were hypoperfused compared with NAWM to the same degree in EC and AD participants, which suggests a common WMH etiology between groups. However, white matter locations that were likely to contain WMH tended to be hypoperfused in ADs compared with healthy aging. This finding is suggestive of AD-specific pathology that reduces the perfusion at anatomic locations susceptible to the formation of WMH through either the neurodegenerative process or AD-related vasculopathy or both.","Aged;Aging/pathology/ physiology;Alzheimer Disease/ complications/diagnosis/pathology/radionuclide imaging;Brain/ blood supply/pathology;Cerebral Small Vessel Diseases/ complications/ diagnosis/pathology/radionuclide;imaging;Cysteine/analogs & derivatives;Female;Humans;Leukoaraiosis/complications/pathology/radionuclide imaging;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Neuroimaging;Organotechnetium Compounds;Radiopharmaceuticals;Tomography, Emission-Computed, Single-Photon","Makedonov, I.;Black, S. E.;MacIntosh, B. J.",2013,Feb,10.1111/j.1468-1331.2012.03785.x,0,
2708,Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease,"There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.",,"Mak, E.;Su, L.;Williams, G. B.;O'Brien, J. T.",2015,Aug,10.1016/j.parkreldis.2015.05.013,0,
2709,White Matter Hyperintensities and Mild Cognitive Impairment in Parkinson's Disease,"OBJECTIVES: The clinical implications of white matter hyperintensities (WMH) in non-demented Parkinson's disease (PD) have not been thoroughly examined. To address this, we investigated the spatial distribution of WMH and their regional predilection in non-demented patients with mild PD. METHODS: Cognitive assessments classified the sample into patients with mild cognitive impairment (PD-MCI, n = 25) and patients with no cognitive impairment (PD-NCI, n = 65) based on the recent formal Movement Disorder Task Force diagnostic criteria. The mean age was 65.1 +/- 7.7 years, disease duration was 5.3 +/- 3.9 years, and Hoehn and Yahr stage was 1.9 +/- .4. WMHs were outlined on T2-weighted imaging using a semi-automated technique. The spatial distribution of WMHs were compared between PD-MCI and PD-NCI using voxel-wise lesion probability maps (LPM). General linear models examined the associations between spatially specific WMHs and cognitive domains. RESULTS: LPM analyses showed significant differences in the spatial distribution of WMH in PD-MCI compared to PD-NCI in widespread regions of the brain (P < .05). PD-MCI demonstrated significantly greater total and periventricular WMHs compared to PD-NCI (P </= .02). Spatial distribution of WMHs was also significantly associated with global cognition, performance on the Frontal Assessment Battery and Fruit Fluency (P < .05). CONCLUSIONS: Voxel-wise LPM analysis revealed differences in the spatial distribution of WMH between PD-MCI and PD-NCI patients, particularly in the periventricular regions. A more widespread extent of WMH might be indicative of cognitive deterioration. Our findings warrant further longitudinal investigation into the importance of WMH spatial distribution as a predictor for conversion from PD to PD with dementia.",,"Mak, E.;Dwyer, M. G.;Ramasamy, D. P.;Au, W. L.;Tan, L. C.;Zivadinov, R.;Kandiah, N.",2015,Sep-Oct,10.1111/jon.12230,0,
2710,The segregated connectome of late-life depression: a combined cortical thickness and structural covariance analysis,"Late-life depression (LLD) has been associated with both generalized and focal neuroanatomical changes including gray matter atrophy and white matter abnormalities. However, previous literature has not been consistent and, in particular, its impact on the topology organization of brain networks remains to be established. In this multimodal study, we first examined cortical thickness, and applied graph theory to investigate structural covariance networks in LLD. Thirty-three subjects with LLD and 25 controls underwent T1-weighted, fluid-attenuated inversion recovery and clinical assessments. Freesurfer was used to perform vertex-wise comparisons of cortical thickness, whereas the Graph Analysis Toolbox (GAT) was implemented to construct and analyze the structural covariance networks. LLD showed a trend of lower thickness in the left insular region (p < 0.001 uncorrected). In addition, the structural network of LLD was characterized by greater segregation, particularly showing higher transitivity (i.e., measure of clustering) and modularity (i.e., tendency for a network to be organized into subnetworks). It was also less robust against random failure and targeted attacks. Despite relative cortical preservation, the topology of the LLD network showed significant changes particularly in segregation. These findings demonstrate the potential for graph theoretical approaches to complement conventional structural imaging analyses and provide novel insights into the heterogeneous etiology and pathogenesis of LLD.",Brain network;Dementia;Depression;Graph theory;Imaging;Late-life depression;Psychiatry,"Mak, E.;Colloby, S. J.;Thomas, A.;O'Brien, J. T.",2016,Dec,,0,
2711,"Subcortical atrophy is associated with cognitive impairment in mild Parkinson disease: a combined investigation of volumetric changes, cortical thickness, and vertex-based shape analysis","BACKGROUND AND PURPOSE: The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction. MATERIALS AND METHODS: The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models. RESULTS: Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness. CONCLUSIONS: Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for Parkinson disease-mild cognitive impairment.","Aged;Atrophy/pathology;Brain/ pathology;Female;Gray Matter/pathology;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mild Cognitive Impairment/etiology/ pathology;Neuropsychological Tests;Parkinson Disease/ pathology/psychology","Mak, E.;Bergsland, N.;Dwyer, M. G.;Zivadinov, R.;Kandiah, N.",2014,Dec,10.3174/ajnr.A4055,0,
2712,Birth size and brain function 75 years later,"BACKGROUND: There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations. METHODS: Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ?75 years later underwent an examination that included brain MRI and extensive cognitive assessment. RESULTS: Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m3 ), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; bs (95% confidence intervals) were 21.0 (21.9 to 20.0) and 20.5 (21.0 to 20.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (b [95% confidence interval]: 20.136 [20.235 to 20.036] and 20.077 [20.153 to 20.001]). CONCLUSIONS: This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels.",aged;article;body weight;brain function;brain size;brain tissue;cephalometry;cognition;cognitive defect;cohort analysis;controlled study;dementia;female;human;low birth weight;major clinical study;male;nuclear magnetic resonance imaging;priority journal;social status;third trimester pregnancy;uterus;white matter,"Majon, M.;Sigurdur, S.;Olafur, K.;Palmi, V. J.;Melissa, G.;Von Mikaela, B. B.;Ingibjorg, G.;Inga, T.;Tamara, B. H.;Van Mark, B.;Vilmundur, G.;Lenore, J. L.",2014,,10.1542/peds.2014-1108,0,
2713,Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: A cross-sectional study,"Background: Previous studies have identified effects of age and vascular risk factors on brain injury in elderly individuals. We aimed to establish whether the effects of high blood pressure in the brain are evident as early as the fifth decade of life. Methods: In an investigation of the third generation of the Framingham Heart Study, we approached all participants in 2009 to ask whether they would be willing to undergo MRI. Consenting patients underwent clinical assessment and cerebral MRI that included T1-weighted and diffusion tensor imaging to obtain estimates of fractional anisotropy, mean diffusivity, and grey-matter volumes. All images were coregistered to a common minimum deformation template for voxel-based linear regressions relating fractional anisotropy, mean diffusivity, and grey-matter volumes to age and systolic blood pressure, with adjustment for potential confounders. Findings: 579 (14·1%) of 4095 participants in the third-generation cohort (mean age 39·2 years, SD 8·4) underwent brain MRI between June, 2009 and June, 2010. Age was associated with decreased fractional anisotropy and increased mean diffusivity in almost all cerebral white-matter voxels. Age was also independently associated with reduced grey-matter volumes. Increased systolic blood pressure was linearly associated with decreased regional fractional anisotropy and increased mean diffusivity, especially in the anterior corpus callosum, the inferior fronto-occipital fasciculi, and the fibres that project from the thalamus to the superior frontal gyrus. It was also strongly associated with reduced grey-matter volumes, particularly in Brodmann's area 48 on the medial surface of the temporal lobe and Brodmann's area 21 of the middle temporal gyrus. Interpretation: Our results suggest that subtle vascular brain injury develops insidiously during life, with discernible effects even in young adults. These findings emphasise the need for early and optimum control of blood pressure. Funding: National Institutes of Health and National Heart, Lung, and Blood Institute; National Institute on Aging; and National Institute of Neurological Disorders and Stroke. © 2012 Elsevier Ltd.",,"Maillard, P.;Seshadri, S.;Beiser, A.;Himali, J. J.;Au, R.;Fletcher, E.;Carmichael, O.;Wolf, P. A.;DeCarli, C.",2012,December,,0,
2714,Effects of arterial stiffness on brain integrity in young adults from the framingham heart study,"Background and Purpose-Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults. Methods-One thousand nine hundred three participants from the Framingham Heart Study Third Generation (mean age, 46±8.7 years) had complete tonometry measurements and brain magnetic resonance imaging (T1-weighted and diffusion tensor imaging). Tonometry measures included carotid-femoral pulse wave velocity, augmentation index, carotidbrachial pressure amplification, and central pulse pressure. Fractional anisotropy and GM density images were computed from diffusion tensor imaging and T1 images. Registration to a common anatomic template enabled voxel-based linear regressions relating measures of fractional anisotropy and GM to tonometry measures, adjusting for relevant covariables. Results-Higher carotid-femoral pulse wave velocity was associated with lower regional fractional anisotropy, including the corpus callosum and the corona radiata (8.7 and 8.6 cc, respectively, P<0.001), as well as lower GM density in the thalamus region (0.9 cc, P<0.001). Analyses did not reveal significant associations between other tonometry measures and fractional anisotropy or GM. Conclusions-Among young healthy adults, higher aortic stiffness was associated with measures of reduced white matter and GM integrity in areas implicated in cognitive decline and Alzheimer's disease. Greater aortic stiffness may result in subclinical vascular brain injury at ages much younger than previously described.",,"Maillard, P.;Mitchell, G. F.;Himali, J. J.;Beiser, A.;Tsao, C. W.;Pase, M. P.;Satizabal, C. L.;Vasan, R. S.;Seshadri, S.;De Carli, C.",2016,2016,,0,
2715,White matter hyperintensities and their penumbra lie along a continuum of injury in the aging brain,"Background and Purpose: Aging is accompanied by clinically silent cerebral white matter injury identified through white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR)-and diffusion tensor imaging-based measures of white matter integrity. The temporal course of FLAIR and diffusion tensor imaging changes within WMHs and their less-injured periphery (ie, their penumbra), however, has not been fully studied. We used longitudinal diffusion tensor imaging and FLAIR to explore these changes. METHODS-: One hundred fifteen participants, aged 73.7±6.7 years, received clinical evaluations and MRIs on 2 dates. WMHs and fractional anisotropy (FA) maps were produced from FLAIR and diffusion tensor imaging and coregistered to a standardized space. Each distinct WMH was categorized as growing, stagnant, or noncontiguous incident. The penumbra of each WMH was similarly categorized as corresponding to a stagnant, growing, or noncontiguous incident WMH. Linear mixed-effect models were used to assess whether FA and FLAIR measurements changed between baseline and follow-up and differed between tissue categories. RESULTS-: Baseline FA differed significantly by tissue category, with the following ordering of categories from highest to lowest FA: penumbra of noncontiguous incident, then stagnant, then growing WMHs; noncontiguous incident, then stagnant, then growing WMHs. Despite differences in baseline values, all tissue categories experienced declines in FA over time. Only noncontiguous incident WMHs showed significant FLAIR signal increases over time, and FLAIR signal significantly decreased in stagnant WMHs. CONCLUSIONS-: WMHs and their penumbra vary in severity and together span a continuous spectrum of white matter injury that worsens with time. FLAIR fails to capture this continuous injury process fully but does identify a subclass of lesions that seem to improve over time. © 2014 American Heart Association, Inc.",,"Maillard, P.;Fletcher, E.;Lockhart, S. N.;Roach, A. E.;Reed, B.;Mungas, D.;Decarli, C.;Carmichael, O. T.",2014,June,,0,
2716,White matter hyperintensity penumbra,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood. METHODS: Two hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors. RESULTS: Fractional anisotropy was found to decrease as neighborhood white matter injury increased (beta = -0.0017/%, P < 0.0001) with an accelerated rate (P < 0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (P < 0.001). CONCLUSIONS: WMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.",Aged;Anisotropy;Brain/ pathology;Cardiology;Cardiovascular Diseases/diagnosis;Case-Control Studies;Cognition Disorders/pathology;Diffusion Tensor Imaging/methods;Female;Humans;Leukoencephalopathies/ pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Risk,"Maillard, P.;Fletcher, E.;Harvey, D.;Carmichael, O.;Reed, B.;Mungas, D.;DeCarli, C.",2011,Jul,10.1161/strokeaha.110.609768,0,
2717,Longitudinal follow-up of individual white matter hyperintensities in a large cohort of elderly,"Introduction: We report on a method for the longitudinal follow-up of individual white matter hypersignals (WMH) and on its application to the study of WMH natural evolution in a cohort of 1,118 elderly over a 4-year period. Materials and methods: For each subject, automated WMH detection was performed on T2-weighted MR images acquired both at baseline and at follow-up after registration in a common space. The detection algorithm was designed both to track WMH previously existing at baseline and to identify newly formed WMH. Results: The average annual change in WMH load was found to be 0.25 cm (3)/year, 36% of this change being attributable to newly formed WMH. Quantitative analyses showed that change in WMH was mainly explained by progression of juxtaventricular and periventricular WMH while the load of WMH in the deep white matter zones was found stable over 4 years of the study. Statistical parametric mapping confirmed these spatial WMH change distributions in the juxta- and periventricular zones. High blood pressure was not a significant predictor of the annual change in WMH. Conclusion: This study proposes a new scheme for the longitudinal study of WMH change by dissociating worsening of existent WMH from surfacing of new WMH and may thus contribute to help understanding and characterizing the neurological and etiological bases of these two processes and their potential differences. © 2008 Springer-Verlag.",,"Maillard, P.;Crivello, F.;Dufouil, C.;Tzourio-Mazoyer, N.;Tzourio, C.;Mazoyer, B.",2009,April,,0,
2718,Cooccurrence of vascular risk factors and late-life white-matter integrity changes,"Hypertension, hyperlipidemia, and diabetes are increasingly prevalent with advancing age and have been shown to cause white-matter (WM) injury that may contribute to dementia risk. However, cumulative and over time effects of these medical illnesses have not been systematically examined. One hundred twenty-one cognitively normal old participants received comprehensive clinical evaluations and brain diffusion tensor imaging on 2 occasions. Clinical history and medical treatment of diabetes, hypertension, and hyperlipidemia were assessed at both evaluations. We examined whether exposure to a greater number of vascular risk factors (VRFs) was associated with greater rate of WM integrity change using longitudinal differences in fractional anisotropy (FA). Compared with individuals with no VRF, individuals with 1 VRF did not exhibit significantly different change in FA. However, those with >/= 2 VRFs had greater decrease in FA within multiple WM regions including the splenium of the corpus callosum. The accumulation of VRF increasingly affected WM integrity, particularly in areas known to be injured in patients with mild cognitive impairment and dementia.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Anisotropy;Corpus Callosum/pathology;Dementia/etiology/pathology;Diabetes Mellitus/ pathology;Diffusion Tensor Imaging;Humans;Hyperlipidemias/ pathology;Hypertension/ pathology;Longitudinal Studies;Middle Aged;Mild Cognitive Impairment/pathology;Risk Factors;White Matter/ pathology;Young Adult","Maillard, P.;Carmichael, O. T.;Reed, B.;Mungas, D.;DeCarli, C.",2015,Apr,10.1016/j.neurobiolaging.2015.01.007,0,
2719,FLAIR and diffusion MRI signals are independent predictors of white matter hyperintensities,"BACKGROUND AND PURPOSE: WMH, associated with cognitive decline and cardiovascular risk factors, may represent only the extreme end of a more widespread continuous WM injury process that progresses during aging and is poorly understood. We investigated the ability of FLAIR and DTI to characterize the longitudinal course of WMH development. MATERIALS AND METHODS: One hundred nineteen participants (mean age, 74.5 +/- 7.4), including cognitively healthy elders and subjects diagnosed with Alzheimer disease and mild cognitive impairment, received a comprehensive clinical evaluation and brain MR imaging, including FLAIR and DTI on 2 dates. The risk for each baseline normal-appearing WM voxel to convert into WMH was modeled as a function of baseline FA (model M1) and both baseline FA and standardized FLAIR (M2). Sensitivity, specificity, accuracy, and AUC for predicting conversion to WMH were compared between models. RESULTS: Independent of clinical diagnosis, lower baseline FA (P < .001, both models) and higher baseline FLAIR intensity (P < .001, M2) were independently associated with increased risk for conversion from normal WM to WMH. M1 exhibited higher sensitivity but lower specificity, accuracy, and AUC compared with M2. CONCLUSIONS: These findings provide further evidence that WMH result from a continuous process of WM degeneration with time. Stepwise decreases in WM integrity as measured by both DTI and FLAIR were independently associated with stepwise increases in WMH risk, emphasizing that these modalities may provide complementary information for understanding the time course of aging-associated WM degeneration.","Aged;Algorithms;Alzheimer Disease/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/ pathology;Prognosis;Reproducibility of Results;Sensitivity and Specificity","Maillard, P.;Carmichael, O.;Harvey, D.;Fletcher, E.;Reed, B.;Mungas, D.;DeCarli, C.",2013,Jan,10.3174/ajnr.A3146,0,
2720,Coevolution of white matter hyperintensities and cognition in the elderly,"OBJECTIVE: To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). METHODS: A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). RESULTS: WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures. CONCLUSIONS: Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences.","Aged;Aged, 80 and over;Aging/*pathology;Alzheimer Disease/*pathology;Brain/*pathology;Executive Function;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory, Episodic;Mild Cognitive Impairment/*pathology;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Psychiatric Status Rating Scales","Maillard, P.;Carmichael, O.;Fletcher, E.;Reed, B.;Mungas, D.;DeCarli, C.",2012,Jul 31,10.1212/WNL.0b013e3182617136,0,
2721,Widespread white matter degeneration preceding the onset of dementia,"BACKGROUND: Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer's disease (AD). METHODS: Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups. RESULTS: FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P < .05). The extent of increases was similar to that found comparing AD with controls. CONCLUSION: Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.","Aged;Aged, 80 and over;Anisotropy;Dementia/ etiology;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/complications;Nerve Degeneration/ complications/pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;White Matter/ pathology","Maier-Hein, K. H.;Westin, C. F.;Shenton, M. E.;Weiner, M. W.;Raj, A.;Thomann, P.;Kikinis, R.;Stieltjes, B.;Pasternak, O.",2015,May,10.1016/j.jalz.2014.04.518,0,
2722,"Lobar brain hemorrhages and white matter changes: Clinical, radiological and laboratorial profiles","BACKGROUND: White matter changes have several histopathologic correlates including cerebral amyloid angiopathy (CAA). The aim of this study was to characterize the clinical, laboratorial and neuroradiological profile of a CAA-related lobar hemorrhages case series. METHODS: A cohort of 50 consecutive patients with cerebral lobar hemorrhages was studied and clinical, radiological data and ApoE polymorphisms were analyzed. White matter changes were graded and microbleeds were characterized according to number and location using T2* MRI. RESULTS: A statistically significant association was found between the prestroke cognitive performance and poststroke dementia and between hemorrhage volume and mortality. More severe white matter changes were found in probable CAA when comparing to possible CAA. The most prominent white matter lesions are associated with the presence and the number of microbleeds. The frequency of APOE epsilon 2 and epsilon 4 alleles was higher in this cohort when compared to a Northern Portuguese population. CONCLUSION: White matter changes are frequent in lobar hemorrhage patients and are associated with cortical microbleeds, the radiological hallmark of CAA. Therefore, white matter changes may be the sole phenotype of CAA and, potentially, involved in the pre-stroke cognitive impairment presented by the patients, which are genetically distinct from the population in general.","Aged;Apolipoproteins E/genetics;Brain/*pathology;Cerebral Amyloid Angiopathy/complications/genetics/*pathology;Cerebral Hemorrhage/etiology/genetics/*pathology;Cognition Disorders/etiology/genetics/pathology;Cohort Studies;Diffusion Magnetic Resonance Imaging;Female;Humans;Leukoaraiosis/complications/genetics/*pathology;Male;Tomography, X-Ray Computed","Maia, L. F.;Vasconcelos, C.;Seixas, S.;Magalhaes, R.;Correia, M.",2006,,10.1159/000093245,0,
2723,Weight Rich-Club Analysis in the White Matter Network of Late-Life Depression with Memory Deficits,"Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.",connectome;graph theory;late-life depression;memory deficits;rich-club;white matter,"Mai, N.;Zhong, X.;Chen, B.;Peng, Q.;Wu, Z.;Zhang, W.;Ouyang, C.;Ning, Y.",2017,,,0,
2724,Effect of Huangqi injection on the change of 24-hour dynamic blood pressure in elderly patients with cerebral infarction at convalescent stage. [Chinese],"Aim: To observe the changes of 24-hour dynamic blood pressure (BP) adding. Huangqi injection into the elderly patients with cerebral infarction, improve the clinical effectiveness and raise ability of daily living activity. Methods: 1 According to the proper order of time, a total of 102 inpatients aging 60-80 years were selected from the Department of Geriatrics in the First Affiliated Hospital of Guangxi College of Traditional Chinese Medicine from January 2002 to December 2005. They were diagnosed by brain CT or MRI as cerebral infarction at convalescent stage, accompanying neurological deficit but without conscious disturbance, in accordance with main points of diagnosing all kinds of cerebrovascular diseases by the Fourth Academic Conference of National Cerebrovascular Diseases, and they were divided randomly into therapy group and control group, each containing 51 patients. 2 Both groups were given the treatment of symptom and rehabilitation: oral administration of Aspirin enteric-coated tablets of 100 mg, once a day for 30 days; intravenous injection of 250 mL saline plus 60 mg brain protein hydrolysate, once a day for 30 days. Rehabilitation training was mainly Bobath, including good posture on the bed, passive activity and active activity of affected joints, turning and sitting training, sitting position and standing balance training, walking training and training of daily living activity, 45 minutes for each item, two times a day and 10 times a week, totally for 4 weeks. In order to state the BP, both groups received Nifedipine extended release tablet at 10 mg, once every 12 hours and totally 60 times. 3 In addition, the therapy group received 100 mL Huangqi injection containing 0.5 g/mL crude materials, once daily. The treatment period included 15 days as a course and successively for two periods. 4 The 24-hour dynamic BP was examined before and after treatment: automeasuring once every 30 minutes during 8:00-20:00 at day and 20:00-8:00 at night. The subjects were required to accord the normal cycle of activity and rest. Meanwhile, the range of BP descents and the odds ratio of decompression trough and peak (T/P) were observed to assess the clinical effectiveness of cerebral infarction, neurological deficits and ability of daily life activity. Results: Totally 102 inpatients with cerebral infarction at convalescent stage were involved in the result analysis. 1 Changes of 24-hour dynamic BP before and after treatment: In therapy group, the range of BP descent was similar, while the BP was stable and heart rate was a little increased. T/P of decompression was systolic BP of 71.2% and diastolic BP of 78.7%; In control group, the range of BP descent was obviously different between ay day and at night, and heart rate was changed with BP. T/P of decompression was systolic BP of 50.3% and diastolic BP of 58.6%. Both groups showed the significantly decreased levels of 24-hour BP. 2 Evaluation on the curative effect of cerebral infarction: The total valid rate was similar in two groups (96%, 82%, P > 0.05), while the rates of full recovery and striking utility were significantly higher in therapy group than in control group (80%, 61%, P < 0.05). 3 Compared with control group, the neurological deficit score was markedly decreased in the therapy group after 30-day treatment [(39.72+4.23), (32.53+4.61) points, t=8.207, P < 0.01], whereas the activity of daily living score by Barthel index was markedly increased (32.46+13.28, 42.38+13.72, t=3.710, P < 0.01). 4 Adverse event and side effect: There was no adverse drug reaction in the therapy group, and 3 patients of control group appeared mild headache at the initial treatment. Conclusion: Huangqi injection will state the BP of elderly patients with cerebral infarction at convalescent stage, progress the clinical effectiveness of descending BP, improve neurological deficit and rise the activity of daily living, suggesting the great rehabilitation and second prevention of adding Huangqi injection on the elderly patients with cerebral infarction.",adult aged article Barthel index blood pressure monitoring body posture brain infarction dt [Drug Therapy] brain infarction rh [Rehabilitation] brain infarction th [Therapy] clinical trial computer assisted tomography controlled clinical trial controlle,"Mai, L. S.;Huang, L. W.;Qian, H. L.;Mo, X. Y.;Li, L.",2006,,,0,
2725,Longitudinal diffusion tensor imaging in frontotemporal dementia,"OBJECTIVE: Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD). METHODS: Twenty-three patients with bvFTD (12 having genetic mutations), and 18 age-matched control participants were assessed using DTI and neuropsychological batteries at baseline and ~1.3 years later. Baseline and follow-up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated. RESULTS: In the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: -6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: -7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: -6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: -6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change. INTERPRETATION: Serial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials.",Aged;Anisotropy;Brain/ pathology;Case-Control Studies;Cognition Disorders/diagnosis/etiology;Diffusion Tensor Imaging;Disease Progression;Female;Frontotemporal Dementia/complications/ diagnosis/genetics;Humans;Longitudinal Studies;Male;Middle Aged;Neuropsychological Tests;Sensitivity and Specificity;White Matter/ pathology,"Mahoney, C. J.;Simpson, I. J.;Nicholas, J. M.;Fletcher, P. D.;Downey, L. E.;Golden, H. L.;Clark, C. N.;Schmitz, N.;Rohrer, J. D.;Schott, J. M.;Zhang, H.;Ourselin, S.;Warren, J. D.;Fox, N. C.",2015,Jan,10.1002/ana.24296,0,
2726,Profiles of white matter tract pathology in frontotemporal dementia,"Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies.","Alzheimer Disease/diagnosis/ pathology;Anisotropy;Atrophy;Brain/ pathology;Cohort Studies;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/diagnosis/genetics/ pathology;Genotyping Techniques;Gray Matter/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Nerve Fibers, Myelinated/ pathology;Proteins/genetics;Sensitivity and Specificity;White Matter/ pathology;tau Proteins/genetics","Mahoney, C. J.;Ridgway, G. R.;Malone, I. B.;Downey, L. E.;Beck, J.;Kinnunen, K. M.;Schmitz, N.;Golden, H. L.;Rohrer, J. D.;Schott, J. M.;Rossor, M. N.;Ourselin, S.;Mead, S.;Fox, N. C.;Warren, J. D.",2014,Aug,10.1002/hbm.22468,0,
2727,White matter tract signatures of the progressive aphasias,"The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity.","Aged;Aphasia, Primary Progressive/ metabolism/ pathology;Cohort Studies;Cross-Sectional Studies;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ metabolism/ pathology","Mahoney, C. J.;Malone, I. B.;Ridgway, G. R.;Buckley, A. H.;Downey, L. E.;Golden, H. L.;Ryan, N. S.;Ourselin, S.;Schott, J. M.;Rossor, M. N.;Fox, N. C.;Warren, J. D.",2013,Jun,10.1016/j.neurobiolaging.2012.12.002,0,
2728,Values of ambulatory blood pressure monitoring for prediction of cognitive function impairment in elderly hypertensive patients,"Background: Hypertension has been shown to carry an increased risk not only for cerebrovascular stroke but also for cognitive impairment and dementia. Ambulatory blood pressure monitoring (ABPM) is a good predictor of cardiac, renal, and cerebral disease in middle-aged and older people with hypertension. Patients and methods: The study included 77 elderly (mean age: 69. years) subjects. Based on the history of hypertension, office blood pressure, and ABPM, patients were classified into 2 groups, Group I: 22 persons as a control group and Group II: 55 hypertensive patients. The hypertensive group was further sub classified by using data of ABPM into dippers and non-dippers. Both groups were subjected to clinical examination, laboratory analysis, ABPM, Transthoracic Echocardiographic Examination, brain magnetic resonance imaging (MRI) and mini-mental state examination (MMSE) of their cognitive function. Results: There was a statistically significant positive correlation between the cerebral MRI score and each of the average 24-h systolic, diastolic and mean arterial blood pressure, average morning systolic, diastolic, mean arterial blood pressure, average night systolic, diastolic and mean arterial blood pressure. There was also a statistically significant negative correlation between the MMSE score and the previous parameters. A non significant correlation was noted between the cerebral MRI score and the office systolic and diastolic blood pressure in hypertensive group. Conclusion: The study demonstrated that hypertensive patients diagnosed by ABPM have significantly more impaired cognitive function than control subjects as proved by the mini-mental state examination and brain MRI score of white matter disease.",,"Mahmoud, K. S.;Ismail, T. T.;Saad, M.;Mohsen, L. A.;Ibrahiem, M. A.;Fadeel, N. A. A.;Sotouhy, A.",2015,2015,,0,
2729,White matter impairment in rett syndrome: Diffusion tensor imaging study with clinical correlations,"BACKGROUND AND PURPOSE: RTT, caused by mutations in the methyl CPG binding protein 2 (MeCP2) gene, is a disorder of neuronal maturation and connections. Our aim was to prospectively examine FA by DTI and correlate this with certain clinical features in patients with RTT. MATERIALS AND METHODS: Thirty-two patients with RTT underwent neurologic assessments and DTI. Thirty-seven age-matched healthy female control subjects were studied for comparison. With use of a 1.5T MR imaging unit, DTI data were acquired, and FA was evaluated to investigate multiple regional tract-specific abnormalities in patients with RTT. RESULTS: In RTT, significant reductions in FA were noted in the genu and splenium of the corpus callosum and external capsule, with regions of significant reductions in the cingulate, internal capsule, posterior thalamic radiation, and frontal white matter. In contrast, FA of visual pathways was similar to control subjects. FA in the superior longitudinal fasciculus, which is associated with speech, was equal to control subjects in patients with preserved speech (phrases and sentences) (P = .542), whereas FA was reduced in those patients who were nonverbal or speaking only single words (P < .001). No correlations between",,"Mahmood, A.;Bibat, G.;Zhan, A. L.;Izbudak, I.;Farage, L.;Horska, A.;Mori, S.;Naidu, S.",2010,February,,0,
2730,Diffusion tensor imaging in preclinical Huntington's disease,"Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects. © 2008 The Author(s).",,"Magnotta, V. A.;Kim, J.;Koscik, T.;Beglinger, L. J.;Espinso, D.;Langbehn, D.;Nopoulos, P.;Paulsen, J. S.",2009,March,,0,
2731,DTI measurements for Alzheimer's classification,"Diffusion tensor imaging (DTI) is a promising imaging technique that provides insight into white matter microstructure integrity and it has greatly helped identifying white matter regions affected by Alzheimer's disease (AD) in its early stages. DTI can therefore be a valuable source of information when designing machine-learning strategies to discriminate between healthy control (HC) subjects, AD patients and subjects with mild cognitive impairment (MCI). Nonetheless, several studies have reported so far conflicting results, especially because of the adoption of biased feature selection strategies. In this paper we firstly analyzed DTI scans of 150 subjects from the Alzheimer's disease neuroimaging initiative (ADNI) database. We measured a significant effect of the feature selection bias on the classification performance (p-value < 0.01), leading to overoptimistic results (10% up to 30% relative increase in AUC). We observed that this effect is manifest regardless of the choice of diffusion index, specifically fractional anisotropy and mean diffusivity. Secondly, we performed a test on an independent mixed cohort consisting of 119 ADNI scans; thus, we evaluated the informative content provided by DTI measurements for AD classification. Classification performances and biological insight, concerning brain regions related to the disease, provided by cross-validation analysis were both confirmed on the independent test.",,"Maggipinto, T.;Bellotti, R.;Amoroso, N.;Diacono, D.;Donvito, G.;Lella, E.;Monaco, A.;Antonella Scelsi, M.;Tangaro, S.",2017,Mar 21,,0,
2732,Brain biopsy in neurologic decline of unknown etiology,"Brain biopsies have an uncertain role in the diagnosis of patients with dementia or neurologic decline of unknown etiology. They are often performed only after an exhaustive panel of less invasive tests and procedures have failed to provide a definitive diagnosis. The objective of this study was to evaluate the sensitivity of brain biopsies in this patient group through the retrospective analysis of 53 brain biopsies performed for neurologic disease of unknown etiology at a single tertiary care institution between December 2001 and December 2011. Patients with known nonlymphomatous neoplasms thought to be associated with the neurologic symptoms or with immunodeficiency were excluded from the study. Furthermore, the clinical presentation, imaging and laboratory tests were compared between diagnostic groups to identify factors more likely to yield a diagnosis. Sixty percent of the biopsies were diagnostic (32 of 53), with the most common histologic diagnosis of central nervous system lymphoma in 14 of 53 patients (26% of total) followed by infarct in four subjects (7.5%). A few patients were found to have rare and unsuspected diseases such as lymphomatosis cerebri, neurosarcoidosis and neuroaxonal leukodystrophy. Complications from biopsy were uncommon and included hemorrhage and infection with abscess formation at the biopsy site. These results suggest that brain biopsies may be useful in difficult cases in which less invasive measures have been unable to yield a definitive diagnosis.",abscess;Alzheimer disease;biopsy;bleeding;brain biopsy;central nervous system;dementia;diagnosis;diagnosis related group;diseases;etiology;human;imaging;immune deficiency;infarction;infection;laboratory test;leukodystrophy;lymphoma;lymphomatosis;neoplasm;neurologic disease;patient;procedures;sarcoidosis;soft contact lens;tertiary health care;vasculitis,"Magaki, S.;Gardner, T.;Khanlou, N.;Yong, W. H.;Salamon, N.;Vinters, H. V.",2015,,10.1016/j.humpath.2014.12.003,0,2733
2733,Brain biopsy in neurologic decline of unknown etiology,"Brain biopsies have an uncertain role in the diagnosis of patients with dementia or neurologic decline of unknown etiology. They are often performed only after an exhaustive panel of less invasive tests and procedures have failed to provide a definitive diagnosis. The objective of this study was to evaluate the sensitivity of brain biopsies in this patient group through the retrospective analysis of 53 brain biopsies performed for neurologic disease of unknown etiology at a single tertiary care institution between December 2001 and December 2011. Patients with known nonlymphomatous neoplasms thought to be associated with the neurologic symptoms or with immunodeficiency were excluded from the study. Furthermore, the clinical presentation, imaging and laboratory tests were compared between diagnostic groups to identify factors more likely to yield a diagnosis. Sixty percent of the biopsies were diagnostic (32 of 53), with the most common histologic diagnosis of central nervous system lymphoma in 14 of 53 patients (26% of total) followed by infarct in four subjects (7.5%). A few patients were found to have rare and unsuspected diseases such as lymphomatosis cerebri, neurosarcoidosis and neuroaxonal leukodystrophy. Complications from biopsy were uncommon and included hemorrhage and infection with abscess formation at the biopsy site. These results suggest that brain biopsies may be useful in difficult cases in which less invasive measures have been unable to yield a definitive diagnosis.","Adult;Aged;Aged, 80 and over;Biopsy;Brain/ pathology;Central Nervous System Diseases/etiology/ pathology;Central Nervous System Neoplasms/etiology/pathology;Dementia/etiology/pathology;Female;Humans;Male;Middle Aged;Retrospective Studies","Magaki, S.;Gardner, T.;Khanlou, N.;Yong, W. H.;Salamon, N.;Vinters, H. V.",2015,Apr,10.1016/j.humpath.2014.12.003,0,
2734,Transient aphasia and persistent amnesia after surgery for internal carotid artery - Posterior communicating artery aneurysm,"We report a case of transient aphasia and persistent amnesia after clipping of a ruptured cerebral aneurysm to treat a subarachnoid haemorrhage. Postoperatively, aphasia was identified and magnetic resonance imaging (MRI) showed an abnormal intensity area in the left anterior thalamus. Single photon emission computed tomography (SPECT) revealed a wider area of low perfusion surrounding the left thalamus and left frontotemporal lobe than that shown by the MRI. His aphasia resolved over the subsequent 12-week period. He was left with an isolated disturbance of memory; in the absence of any dementia, aphasia or disturbance of consciousness, his condition was classified as one of amnesia. SPECT 14 weeks after admission revealed an area of low perfusion limited to the left thalamus. These findings suggest that the persistence of amnesia in this case was caused by the infarction of the mammillothalamic tract, and the recovery from aphasia may have resulted from the disappearance of surrounding edema. © 2002 Published by Elsevier Science Ltd.",,"Maeshima, S.;Ueyoshi, A.;Tsuura, M.;Takemoto, H.;Itakura, T.;Yoshida, M.;Matsumoto, T.",2002,November,,0,
2735,"Hypouricemia, abnormal renal tubular urate transport, and plasma natriuretic factor(s) in patients with Alzheimer's disease","OBJECTIVE: To study tubular urate transport in Alzheimer's disease (AD) and measure sodium and lithium transport rates in rats exposed to AD plasma. DESIGN: Cross-sectional study in three comparison groups. SETTING: Referral private institution involving outpatient and hospitalized patients. PATIENTS: AD, multi-infarct dementia (MID) and non-demented controls (C) were selected and evaluated by a geriatrician and a psychiatrist according to availability and willingness to participate in the study. Demented patients had brain imaging, categorized according to NINCDS-DSM III criteria, and had Mini-mental status examination (MMSE) scores determined. INTERVENTIONS: Injection of 0.5 mL of plasma I.P. followed 120 minutes later by an IV plasma injection of 0.2 mL priming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague Dawley rats. MEASUREMENTS: Renal clearance studies were performed in subjects and in rats exposed to the plasma of study subjects. We measured serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats. RESULTS: Serum urate was lower and FE urate higher in 18 AD patients compared with six patients with MID, P < 0.05 and P < 0.005, and 11 C, P < 0.02 and P < 0.005, respectively. Higher FE sodium and FE lithium were noted in rats given plasma from 19 AD patients compared with 12 with MID, P < 0.005 and P < 0.0025, and 14 C, P < 0.0025 and P < 0.0005, respectively. FE sodium and FE lithium decreased progressively after serial dilutions of three AD plasmas and FE lithium was negatively correlated with MMSE scores only in AD, r = -0.71 and P < 0.0005. CONCLUSIONS: In AD there is defective tubular urate transport and a plasma natriuretic factor(s). FE sodium and/or FE lithium in rats exposed to plasma of demented patients may differentiate AD from MID and estimate the severity of AD.","Aged;Alzheimer Disease/ complications/diagnosis/metabolism;Animals;Biological Assay;Case-Control Studies;Creatinine/blood/pharmacokinetics/urine;Cross-Sectional Studies;Dementia, Multi-Infarct/complications/diagnosis;Female;Humans;Kidney Function Tests;Kidney Tubules/ metabolism;Lithium/blood/pharmacokinetics/urine;Male;Mental Status Schedule;Metabolic Clearance Rate;Natriuretic Agents/ blood/metabolism/pharmacokinetics;Phosphorus/blood/pharmacokinetics/urine;Potassium/blood/pharmacokinetics/urine;Rats;Rats, Sprague-Dawley;Severity of Illness Index;Sodium/blood/pharmacokinetics/urine;Uric Acid/ blood/metabolism/pharmacokinetics;Water-Electrolyte Imbalance/ blood/etiology/metabolism","Maesaka, J. K.;Wolf-Klein, G.;Piccione, J. M.;Ma, C. M.",1993,May,,0,
2736,Endoscopic gallbladder stenting for acute cholecystitis: A retrospective study of 46 elderly patients aged 65 years or older,"Background: Endoscopic transpapillary pernasal gallbladder drainage and endoscopic gallbladder stenting (EGS) have recently been reported to be useful in patients with acute cholecystitis for whom a percutaneous approach is contraindicated. The aim of this study was to evaluate the efficacy of permanent EGS for management of acute cholecystitis in elderly patients who were poor surgical candidates.Methods: We retrospectively studied 46 elderly patients aged 65 years or older with acute cholecystitis who were treated at Japan Labour Health and Welfare Organization Niigata Rosai Hospital. In 40 patients, acute cholecystitis was diagnosed by transabdominal ultrasonography and computed tomography, while 6 patients were transferred from other hospitals after primary management of acute cholecystitis. All patients underwent EGS, with a 7Fr double pig-tail stent being inserted into the gallbladder. If EGS failed, percutaneous transhepatic gallbladder drainage or percutaneous transhepatic gallbladder aspiration was subsequently performed. The main outcome measure of this study was the efficacy of EGS.Results: Permanent EGS was successful in 31 patients (77.5%) with acute cholecystitis, without any immediate postprocedural complications such as pancreatitis, bleeding, perforation, or cholangitis. The most common comorbidities of these patients were cerebral infarction (n=14) and dementia (n=13). In 30 of these 31 patients (96.7%), there was no recurrence of cholecystitis and 29 patients (93.5%) remained asymptomatic until death or the end of the study period (after 1 month to 5 years).Conclusions: EGS can be effective for elderly patients with acute cholecystitis who are poor surgical candidates and can provide a solution for several years. © 2013 Maekawa et al.; licensee BioMed Central Ltd.",acute cholecystitis;aged;article;asymptomatic disease;brain infarction;cannula;cholangitis;clinical article;clinical effectiveness;comorbidity;computer assisted tomography;death;dementia;duodenoscope;echography;endoscopic gallbladder stenting;endoscopic therapy;equipment design;female;gallbladder perforation;guide wire;human;Japan;male;outcome assessment;pancreatitis;patient transport;percutaneous transhepatic drainage;postoperative hemorrhage;recurrent disease;retrospective study;stent;treatment failure;JF-260V;Radifocus;Tandem XL,"Maekawa, S.;Nomura, R.;Murase, T.;Ann, Y.;Oeholm, M.;Harada, M.",2013,,,0,
2737,Impaired cognition preceding cardiac surgery is related to cerebral ischemic lesions,"Purpose: Cognitive dysfunction is more frequent after cardiac surgery. However, the preoperative cognitive state is seldom assessed when the effects of cardiac surgery on cognition are investigated. Postoperative cognitive dysfunction may be associated with the preoperative cognitive state and the existence of cerebral ischemic lesions in patients who undergo cardiac surgery. Methods: Data were collected prospectively on 362 consecutive patients scheduled to undergo elective cardiac surgery. The brains of all patients were imaged by magnetic resonance imaging (MRI) to assess prior cerebral infarctions, carotid artery stenosis and intracranial arterial stenosis, and diffusion-weighted imaging (DWI) was used to assess acute cerebral ischemia. Patients were classified with impaired cognitive function prior to surgery if their score on the Hasegawa dementia rating scale was <24. Postoperative cognitive dysfunction from baseline was determined using four neuropsychological tests. Results: Prior to surgery 40 patients (11%) were assessed with impaired cognition. Relative to the other patients, these patients were older and less well educated, and they had significantly higher rates of peripheral vascular disease, white matter lesions, cerebral infarction on MRI, carotid artery stenosis and postoperative cognitive dysfunction. Of these 40 cognitively impaired patients, seven (18%) had cerebral ischemia, based on DWI images before surgery; in comparison, nine of the 322 patients (3%) without preoperative cognitive impairment were found to have abnormalities on the DWI images (P < 0.001). An analysis by stepwise logistic regression demonstrated that the significant risks for preoperative cognitive impairment were advanced age, lower attained level of education, peripheral artery disease, prior cerebral infarctions, and abnormalities on DWI images. Conclusions: These findings suggest that preoperative cognitive impairment associated with cerebral ischemic lesions and an increased risk of postoperative cognitive dysfunction existed in our patient cohort undergoing cardiac surgery. © 2011 Japanese Society of Anesthesiologists.",,"Maekawa, K.;Goto, T.;Baba, T.;Yoshitake, A.;Katahira, K.;Yamamoto, T.",2011,June,,0,
2738,A case of isolated CNS sarcoidosis with diffuse confluent high intensity lesions at bilateral deep white matter,"We reported a 60-year-old woman who suffered from isolated neurosarcodosis. She was presenting comprehensive dysfunction and intermittent high fever. In several months she gradually developed dysorientation, amnesia, dementia. However, no focal sign such as paralysis or sensory disturbance was demonstrated. Her blood chemistry showed normal including ACE (angiotensin converting enzyme) and lysozyme. Cerebrospinal fluid revealed elevated mononuclear cells, protein, and decreased glucose level. At first we treated with antibiotics including antiviral drugs in suspect of the infectious encephalomeningitis. But no improvement was observed. The elevation of ACE in spinal fluid made us suspect of neurosarcoidosis. So intravenous predonizoron (1,000 mg) was given, improving. Her high fever and mental disturbance improved. Second spinal fluid showed improvement. During the course her brain MRI revealed new bilateral diffuse confluent high intensity lesions at the deep white matters. Brain biopsy of deep matter at the right anterior lobe showed noncaseating granuloma. Since systemic work-up to detect sarcoidosis did not reveal lesions other than CNS, we considered this patient as having isolated CNS sarcoidosis.",adult;article;brain biopsy;case report;central nervous system;clinical feature;female;granuloma;human;human tissue;laboratory test;nuclear magnetic resonance imaging;sarcoidosis;white matter,"Maeda, K.;Kita, Y.;Uehara, S.;Yamasaki, O.;Rikimaru, M.;Saji, N.;Tabuti, M.;Furumoto, M.",2006,,,0,
2739,White Matter Changes and Cognitive Decline in a Ten-Year Follow-Up Period: A Pilot Study on a Single-Center Cohort from the Leukoaraiosis and Disability Study,"AIMS: To describe the contribution of white matter lesions to the long-term neuropsychological profiles of different groups of clinical diagnoses, and to identify neuropsychological predictors of cognitive impairment in a 10-year follow-up. METHODS: The Lisbon subcohort of the Leukoaraiosis and Disability (LADIS) study was re-evaluated performing a clinical, functional and cognitive evaluation [including Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and ADAS-Cog with the extension for vascular impairment (VADAS-Cog), the 9-word version of the California Verbal Learning Test (CVLT-9), the Trail-Making test and the Stroop test] as well as an MRI scan. Using clinical diagnostic criteria, participants were identified as having no cognitive impairment (NI), cognitive impairment but no dementia (CIND) or dementia (DEM), and the effect of time on clinical diagnosis and neuropsychological profiles was analyzed. RESULTS: From the initial group of 66 participants, 37 out of 41 survivors (90%) were re-evaluated (mean age 81.40 years, 57% women). Fifteen patients (41%) had DEM, 12 (32%) CIND and 10 (27%) NI. Over time, the three groups presented distinct profiles in the MMSE [F2, 62 = 15.85, p = 0.000], ADAS [F2, 62 = 15.85, p = 0.000] and VADAS [F2, 48 = 5.87, p = 0.008]. Logistic regression analysis identified higher scores on MMSE (beta = 1.14, p = 0.03, OR = 3.13, 95% CI 1.09-8.97) as predictors of NI after 10 years of follow-up. CONCLUSION: Higher scores on baseline MMSE were the only neuropsychological predictors of NI after 10 years.",,"Madureira, S.;Verdelho, A.;Moleiro, C.;Santos, C.;Scheltens, P.;Gouw, A.;Ferro, J.",2016,,10.1159/000447121,0,
2740,Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data,"The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.",Aged;Aging/physiology;Alzheimer Disease/diagnosis/psychology;Brain/pathology;Cognition/physiology;*Disability Evaluation;Education;Employment;Female;Humans;Leukoaraiosis/pathology/*psychology;Magnetic Resonance Imaging;Male;Mental Recall/physiology;Neuropsychological Tests/*standards/statistics & numerical data;Psychomotor Performance/physiology;Recognition (Psychology)/physiology;Reference Values;Regression Analysis;Reproducibility of Results;Verbal Behavior/physiology,"Madureira, S.;Verdelho, A.;Ferro, J.;Basile, A. M.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Hennerici, M.;O'Brien, J.;Pantoni, L.;Salvadori, E.;Scheltens, P.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Inzitari, D.",2006,,10.1159/000095381,0,
2741,Mapping ventricular expansion onto cortical gray matter in older adults,"Dynamic changes in the brain's lateral ventricles on magnetic resonance imaging are powerful biomarkers of disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ventricular measures can represent accumulation of diffuse brain atrophy with very high effect sizes. Despite having no direct role in cognition, ventricular expansion co-occurs with volumetric loss in gray and white matter structures. To better understand relationships between ventricular and cortical changes over time, we related ventricular expansion to atrophy in cognitively relevant cortical gray matter surfaces, which are more challenging to segment. In ADNI participants, percent change in ventricular volumes at 1-year (N= 677) and 2-year (N= 536) intervals was significantly associated with baseline cortical thickness and volume in the full sample controlling for age, sex, and diagnosis, and in MCI separately. Ventricular expansion in MCI was associated with thinner gray matter in frontal, temporal, and parietal regions affected by AD. Ventricular expansion reflects cortical atrophy in early AD, offering a useful biomarker for clinical trials of interventions to slow AD progression.",aged;Alzheimer disease;article;brain atrophy;brain cortex;brain cortex atrophy;brain mapping;brain size;cognition;cognitive defect;controlled study;cortical thickness (brain);disease course;disease severity;female;frontal lobe;gray matter;human;lateral brain ventricle;major clinical study;male;neuroimaging;nuclear magnetic resonance imaging;parietal lobe;temporal lobe;volumetry;white matter,"Madsen, S. K.;Gutman, B. A.;Joshi, S. H.;Toga, A. W.;Jack, C. R.;Weiner, M. W.;Thompson, P. M.",2015,,10.1016/j.neurobiolaging.2014.03.044,0,
2742,Mapping ventricular expansion onto cortical gray matter in older adults,"Dynamic changes in the brain's lateral ventricles on magnetic resonance imaging are powerful biomarkers of disease progression in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Ventricular measures can represent accumulation of diffuse brain atrophy with very high effect sizes. Despite having no direct role in cognition, ventricular expansion co-occurs with volumetric loss in gray and white matter structures. To better understand relationships between ventricular and cortical changes over time, we related ventricular expansion to atrophy in cognitively relevant cortical gray matter surfaces, which are more challenging to segment. In ADNI participants, percent change in ventricular volumes at 1-year (N = 677) and 2-year (N = 536) intervals was significantly associated with baseline cortical thickness and volume in the full sample controlling for age, sex, and diagnosis, and in MCI separately. Ventricular expansion in MCI was associated with thinner gray matter in frontal, temporal, and parietal regions affected by AD. Ventricular expansion reflects cortical atrophy in early AD, offering a useful biomarker for clinical trials of interventions to slow AD progression.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Atrophy;Biomarkers;Cerebral Ventricles/ pathology;Disease Progression;Female;Gray Matter/ pathology;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ pathology;Neuroimaging","Madsen, S. K.;Gutman, B. A.;Joshi, S. H.;Toga, A. W.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.",2015,Jan,10.1016/j.neurobiolaging.2014.03.044,0,
2743,Lack of association between prior depressive episodes and cerebral 11C PiB binding,"Depressive symptoms are frequent in Alzheimer's disease (AD), but it is controversial whether depression is a risk factor for AD. This study measured for the first time cortical amyloid-beta (Abeta) levels using [(11)C] Pittsburgh Compound B (PiB) positron emission tomography (PET) in a group of nondemented patients with prior depressive episodes. Twenty-eight elderly patients (mean age 61 years, range 51-75, 18 women) with onset of first depressive episode more than 6 years ago but now remitted from depression and 18 healthy subjects (mean age 61 years, range 50-76, 12 women) were included. All subjects were investigated with cognitive testing, 3T magnetic resonance imaging (MRI) and [(11)C]PiB high resolution research tomography (HRRT) positron emission tomography scan. There was no between-groups difference in [(11)C]PiB binding (p = 0.5) and no associations to number of depressive episodes, cognitive performance, or antidepressant treatment. Patients with late onset of depression had increased severity of white matter lesions (p = 0.04). In this study depressive episodes were not associated with increased levels of [(11)C]PiB. Thus, our results do not support the notion that depressive episodes previously in life are a risk factor for developing AD.",Age of Onset;Aged;Alzheimer Disease/radionuclide imaging;Amyloid beta-Peptides/analysis;Aniline Compounds;Antidepressive Agents/therapeutic use;Cerebrum/ radionuclide imaging;Depression/drug therapy/ radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Positron-Emission Tomography;Radiopharmaceuticals;Risk Factors;Severity of Illness Index;Thiazoles,"Madsen, K.;Hasselbalch, B. J.;Frederiksen, K. S.;Haahr, M. E.;Gade, A.;Law, I.;Price, J. C.;Knudsen, G. M.;Kessing, L. V.;Hasselbalch, S. G.",2012,Oct,10.1016/j.neurobiolaging.2011.11.021,0,
2744,Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study,"BACKGROUND: Different clinical syndromes can arise from Alzheimer's disease (AD) neuropathology, including dementia of the Alzheimer's type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). OBJECTIVE: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. METHODS: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-beta deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. RESULTS: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. CONCLUSION: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.",,"Madhavan, A.;Schwarz, C. G.;Duffy, J. R.;Strand, E. A.;Machulda, M. M.;Drubach, D. A.;Kantarci, K.;Przybelski, S. A.;Reid, R. I.;Senjem, M. L.;Gunter, J. L.;Apostolova, L. G.;Lowe, V. J.;Petersen, R. C.;Jack, C. R.;Josephs, K. A.;Whitwell, J. L.",2015,Oct 18,10.3233/jad-150502,0,
2745,BIPLEDs with complete and rapid recovery in a patient with AIDS encephalopathy,"A 33-year-old male with AIDS (CD4=12), dementia, spasticity, and MRI findings of cerebral atrophy and deep white matter changes was admitted for the treatment of chronic cough and cellulitis of the legs. Two days after admission, the patient exhibited the first seizure of his life - a generalized convulsion lasting five minutes. An EEG obtained 14 hours after the convulsion revealed bilateral independent periodic lateralized epileptiform discharges (BIPLEDs) with prominent asynchrony. CT and MRI showed abnormalities similar to those present one year before. CSF studies obtained the day after the seizure were normal. The only medication started in the hospital prior to the onset of the seizure was intravenous nafcillin. Immediately after the seizure, nafcillin was discontinued and a loading dose of 1500 mg PE of fosphenytoin was given followed by oral maintenance. Another EEG, three days later, demonstrated the complete resolution of BIPLEDs. No other seizures occurred. With antibiotic therapy the cellulitis and pneumonia resolved and, within two weeks, the patient was discharged home on phenytoin. We propose that in patients with AIDS encephalopathy, the occurrence of coma, seizures, and BIPLEDs should not be assumed to be a poor prognostic sign.",aciclovir;alprazolam;ampicillin;antibiotic agent;anticonvulsive agent;antiretrovirus agent;azithromycin;baclofen;ceftriaxone;codeine;cotrimoxazole;fluconazole;fosphenytoin sodium;furosemide;indinavir;lamivudine;nafcillin;paracetamol;sertraline;stavudine;acquired immune deficiency syndrome;adult;article;brain atrophy;brain disease;case report;cellulitis;cerebrospinal fluid analysis;computer assisted tomography;convulsion;electroencephalography;epileptic discharge;human;male;nuclear magnetic resonance imaging;prognosis;seizure;bactrim;crixivan;diflucan;lasix;tylenol;xanax;zoloft,"Mader E, Jr.;Olejniczak, P.;Fisch, B.",2000,,,0,
2746,Repeatability of quantitative sodium magnetic resonance imaging for estimating pseudo-intracellular sodium concentration and pseudo-extracellular volume fraction in brain at 3 T,"The purpose of this study is to assess the repeatability of the quantification of pseudo-intracellular sodium concentration (C1) and pseudo-extracellular volume fraction (alpha) estimated in brain in vivo using sodium magnetic resonance (MRI) at 3 T. Eleven healthy subjects were scanned twice, with two sodium MRI acquisitions (with and without fluid suppression by inversion recovery), and two double inversion recovery (DIR) proton MRI. DIR MRIs were used to create masks of gray and white matter (GM, WM), that were subsequently applied to the C1 and alpha maps calculated from sodium MRI and a tissue three-compartment model, in order to measure the distributions of these two parameters in GM, WM or full brain (GM+WM) separately. The mean, median, mode, standard deviation (std), skewness and kurtosis of the C1 and alpha distributions in whole GM, WM and full brain were calculated for each subject, averaged over all data, and used as parameters for the repeatability assessment. The coefficient of variation (CV) was calculated as a measure of reliability for the detection of intra-subject changes in C1 and alphafor each parameter, while intraclass correlation (ICC) was used as a measure of repeatability. It was found that the CV of most of the parameters was around 10-20% (except for C1 kurtosis which is about 40%) for C1 and alpha measurements, and that ICC was moderate to very good (0.4 to 0.9) for C1 parameters and for some of the alpha parameters (mainly skewness and kurtosis). In conclusion, the proposed method could allow to reliably detect changes of 50% and above of the different measurement parameters of C1 and alphain neuropathologies (multiple sclerosis, tumor, stroke, Alzheimer's disease) compared to healthy subjects, and that skewness and kurtosis of the distributions of C1 and alphaseem to be the more sensitive parameters to these changes.","Adult;Brain/ physiology;Extracellular Space/ metabolism;Female;Healthy Volunteers;Humans;Image Interpretation, Computer-Assisted/methods;Image Processing, Computer-Assisted/methods;Intracellular Space/ metabolism;Magnetic Resonance Imaging/instrumentation/ methods;Male;Reproducibility of Results;Sodium/ metabolism","Madelin, G.;Babb, J.;Xia, D.;Regatte, R. R.",2015,,10.1371/journal.pone.0118692,0,
2747,A chemical shift imaging study on regional metabolite distribution in a CADASIL family,"A chemical shift imaging (CSI) study was performed to directly assess relative concentrations of N-acetylaspartate (NAA), Cho and Cr metabolites in normal- and abnormal-appearing brain tissue of asymptomatic and symptomatic members of a single family with a neuropathologic, genetic and electrophysiological confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The aim of the investigation was to evaluate clinical findings and metabolite abnormalities as early appearance of axonal injury in this syndrome. The main findings related statistically significant decreases in the mean metabolite ratios for NAA/Cr, NAA/Cho and Cho/Cr in the anterior parts in comparison with the posterior parts of the centrum semiovale in symptomatic and asymptomatic patients. The effect was considerably greater in the symptomatic patients, indicating a strong correlation between CSI and pathology results. No differences were found between the two areas in the control group. Although lactate signals were hardly detectable in individual spectra, there was a trend toward increased Lac/Cr values in the anterior parts with respect to the posterior parts in the patient group, with the effect particularly evident in the asymptomatic subjects with the gene mutation.",Adult;Brain/ metabolism;Brain Chemistry/ physiology;CADASIL/ metabolism/physiopathology;Echo-Planar Imaging;Family;Female;Humans;Magnetic Resonance Imaging/statistics & numerical data;Male;Oxygen/blood;Pedigree,"Macri, M. A.;Colonnese, C.;Garreffa, G.;Fattapposta, F.;Restuccia, R.;Bianco, F.;Labruna, L.;Maraviglia, B.",2006,May,10.1016/j.mri.2005.11.002,0,
2748,"11β-hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive decline","Excess cortisol levels are linked with brain atrophy and cognitive decline in older people. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) potently amplifies intracellular glucocorticoid action by converting inert cortisone to active cortisol, but any causal importance in brain aging is unexplored. We tested the hypotheses that higher systemic 11β-HSD1 activity predicts brain atrophy and cognitive decline in older men. In a longitudinal study of 41 men (65-70 years old at baseline) we measured baseline systemic 11β-HSD1 activity, the urinary 5alpha- and 5beta-tetrahydrocortisol to tetrahydrocortisone ratio (ratio of tetrahydrometabolites of cortisol (THFs)/ratio of tetrahydrometabolites of cortisol (THE)), and assessed change in brain atrophy, white matter lesions and cognitive function over 6 years. Baseline THFs/THE correlated negatively with baseline hippocampal volumes (left: r = -0.37; right: r = -0.34; p < 0.05) and positively with ventricular volumes (r = 0.43, p = 0.006) and periventricular white matter lesions (rho = 0.31, p = 0.047). Importantly, baseline THFs/THE but not cortisol predicted increase in ventricular volumes (r = 0.33, p = 0.037) and decline in processing speed (r = -0.55, p = 0.0002) over 6 years. The predictive link between systemic 11β-HSD1 activity and progressive brain atrophy and cognitive decline suggests 11β-HSD1 inhibition as a plausible therapy for brain aging. © 2012 Elsevier Inc.",11beta hydroxysteroid dehydrogenase 1;5alpha tetrahydrocortisol;5beta tetrahydrocortisol;hydrocortisone;tetrahydrocortisol;tetrahydrocortisone;unclassified drug;aged;article;brain atrophy;brain size;cognition;cognitive defect;controlled study;correlation analysis;enzyme activity;human;image analysis;information processing;longitudinal study;male;neuropsychological test;normal human;nuclear magnetic resonance imaging;prediction;priority journal;urinalysis;volunteer;white matter,"MacLullich, A. M. J.;Ferguson, K. J.;Reid, L. M.;Deary, I. J.;Starr, J. M.;Wardlaw, J. M.;Walker, B. R.;Andrew, R.;Seckl, J. R.",2012,,,0,
2749,The effect of subsyndromal symptoms of depression and white matter lesions on disability for individuals with mild cognitive impairment,"Objective: To assess the effect of subsyndromalsymptomsof depression (SSD) onratings of disability for individualswith mild cognitive impairment (MCI). Methods: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ). Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status. Demographic variables included age, education, and gender. Results: SSD individuals had a lower volume of WML and higher frequency of ApoE ε4 alleles than nondepressed participants but the two groups did not differwith respect to other clinical or demographic variables. At baseline, SSD individuals were 1.77 times more likely to have poorer FAQ scores than individuals with no symptoms of depression after controlling for the effect of cognitive functioning, ICV, WML, and ApoE status. The presence of SSD at baseline was not associated with a poorer course of disability outcomes, cognitive functioning, or conversion to dementia over 24 months. Conclusions: SSD demonstrated a significant impact on disability for MCI individuals, who are also at high risk for functional limitations related to neurodegenerative disease. Therefore, the treatment of SSD may represent a significant avenue to reduce the burden of disability in this vulnerable patient population. © 2013 American Association for Geriatric Psychiatry.",,"Mackin, R. S.;Insel, P.;Tosun, D.;Mueller, S. G.;Schuff, N.;Truran-Sacrey, D.;Raptentsetsang, S. T.;Lee, J. Y.;Jack Jr, C. R.;Aisen, P. S.;Petersen, R. C.;Weiner, M. W.",2013,September,,0,
2750,"Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging","OBJECTIVE: To use 1H magnetic resonance spectroscopic imaging to study differences in neuron density (N-acetylaspartate [NAA]), membrane phospholipid metabolites (choline [Cho]), and creatine-containing metabolites (creatine plus phosphocreatine [Cr]) in subjects with Alzheimer's disease (AD), with subcortical ischemic vascular dementia (SIVD), and elderly controls. DESIGN: Cross-sectional, between groups. SETTING: A Veterans Affairs medical center and university memory clinic. PARTICIPANTS: Forty elderly subjects with AD (n = 14), with SIVD (n = 8), and elderly controls (n = 18). MAIN OUTCOME MEASURES: We used 1H magnetic resonance spectroscopic imaging to acquire spectra from a 80 x 100 x 17-mm volume superior to the lateral ventricles. Spectra were analyzed from voxels in anterior, medial, and posterior gray and white matter using nuclear magnetic resonance-1 and the results were compared between groups using repeated measures analysis of variance (ANOVA), Tukey's test, and individual Student's t tests. RESULTS: Using ANOVA, significantly lower levels of NAA/Cho and NAA/Cr and significantly higher levels of Cho/Cr were observed across both gray and white matter voxels in subjects with AD. Using individual Student's t tests, a significantly lower level of NAA/Cho and a higher level of Cho/Cr were observed in the posterior gray matter in subjects with AD. Using ANOVA in subjects with SIVD, significantly lower gray and white matter NAA/Cr levels were observed. Using Tukey's test, the NAA/Cr level was significantly lower in frontal white matter voxels in subjects with SIVD compared with controls. CONCLUSIONS: Our findings in subjects with AD suggest neuron loss in gray matter, axon loss in white matter, and altered Cho metabolism in posterior brain regions. Our findings in subjects with SIVD are consistent with higher levels of creatine-containing metabolites and/or lower levels of NAA in frontal white matter.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism;Analysis of Variance;Aspartic Acid/analogs & derivatives/metabolism;Brain/ metabolism;Brain Ischemia/ complications;Cerebral Cortex/ blood supply;Choline/metabolism;Creatine/metabolism;Cross-Sectional Studies;Dementia, Vascular/etiology/ metabolism;Female;Humans;Magnetic Resonance Spectroscopy;Male;Middle Aged;Nerve Tissue/ metabolism;Phosphocreatine/metabolism;Protons","MacKay, S.;Meyerhoff, D. J.;Constans, J. M.;Norman, D.;Fein, G.;Weiner, M. W.",1996,Feb,,0,
2751,Postmortem findings in a patient with cerebral amyloid angiopathy actively treated with corticosteroid,"We examined histopathological changes in cerebrovascular amyloid deposition in a patient with cerebral amyloid angiopathy receiving corticosteroid therapy. A 69-year-old female developed subacute onset cognitive decline, and magnetic resonance image (MRI) showed subarachnoid hemorrhage with leptomeningeal enhancement. She entered in an apathetic state due to communicating hydrocephalus and a ventricle-peritoneal (V-P) shunt operation was performed. Brain biopsy disclosed multiple cortical microhemorrhages and severe Congophilic angiopathy with positive Aβ-immunoreactivity in most vessels. Inflammatory mononuclear cells surrounded a few severe amyloid-laden leptomeningeal vessels. She received high-dose corticosteroid, which was slowly tapered. She gradually recovered but finally died 1.5 years later with no recurrence of CAA-related hemorrhages. Postmortem examination of the brain showed multiple old microhemorrhages in the cortex and extensive degeneration of cerebral white matter. The cortical and leptomeningeal vascular walls showed a few Congophilic amyloid deposits, but small deposits with Aβ-immunoreactivity were frequently seen. There was no infiltration of inflammatory cells in either leptomeninges or vascular walls. Electron microscopy revealed sparse aggregation of amyloid fibrils in significant numbers of vascular walls. Biochemical analysis disclosed that Aβ1-40-immunoreactive amyloid protein fractions obtained from the patient's leptomeninges were very small in amount. Comparing the previous biopsy findings with those at autopsy, the total disappearance of the inflammatory cell infiltration and diminishing of the cerebrovascular amyloid deposits were noted. © 2012 Informa UK, Ltd.",,"MacHida, K.;Tsuchiya-Suzuki, A.;Sano, K.;Arima, K.;Saito, Y.;Kametani, F.;Ikeda, S. I.",2012,March,,0,
2752,Magnetic resonance imaging in neuronal ceroid lipofuscinosis,"Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders characterized by accumulation of lipofuscin and/or ceroid within the tissues of the body. These entities are manifest by visual, intellectual, and motor deterioration as well as recurrent seizures. Computed tomography has been shown to demonstrate changes of cerebral atrophy in more severely affected patients. Seven patients with neuronal ceroid lipofuscinosis were examined with both computed tomography and magnetic resonance imaging, and the results were correlated with the clinical severity of the disorder. Two less severely affected patients had normal results on computed tomography and magnetic resonance imaging studies. Varying degrees of cerebral atrophy were seen in the remaining five patients with both computed tomography and magnetic resonance imaging. Severity of atrophy correlated with the severity of disability in these patients. Abnormal white matter was seen in the two most severely affected patients only with magnetic resonance imaging. Although the findings in patients with neuronal ceroid lipofuscinosis were nonspecific, the increased sensitivity of magnetic resonance imaging for subtle white matter abnormalities over computed tomography may prove helpful in monitoring the progression of this rare disorder.",,"Machen, B. C.;Williams, J. P.;Lum, G. B.",1987,1987,,0,
2753,A quantitative and qualitative analysis of prion protein immunohistochemical staining in Creutzfeldt-Jakob disease using four anti prion protein antibodies,"Creutzfeldt-Jakob disease (CJD) is the most common spongiform encephalopathy affecting humans. Prion protein (PrP) immunohistochemistry may be useful for studying the localization of prion protein and assessing its role in CJD, the accumulation of a specific protease resistant PrP isoform being apparently pathognomic to the spongiform encephalopathies. However, a number of factors influence the results of immunostaining, making interpretation and comparisons between the staining of different PrP antisera difficult. This study has examined qualitatively and quantitatively the staining produced by four antisera raised to a variety of prion protein homologues in two cases of CJD and two age-matched controls. Quantitative analysis was provided through the use of custom designed image analysis software. Kuru, granular and multicentric plaques, cellular, perivacuolar and white matter PrP deposits were observed in CJD cases with all four antisera. No significant immunostaining was seen in the control tissue. Some antibody specific staining patterns were observed qualitatively; however, quantitative analysis showed statistically significant correlations between all the antisera on the diseased brain tissue. Prion protein immunohistochemistry is thus useful in interpreting patterns of protein distribution in diseased brain but care may be required in interpreting the results of a single antibody.","Aged;Antibodies;Antibody Specificity;Brain/ pathology;Creutzfeldt-Jakob Syndrome/ pathology;Female;Humans;Immunohistochemistry/methods;Male;Middle Aged;Organ Specificity;Prions/ analysis;Reference Values;Reproducibility of Results;Sensitivity and Specificity;Statistics, Nonparametric","MacDonald, S. T.;Sutherland, K.;Ironside, J. W.",1996,Mar,,0,
2754,On the white matter lesions of the Creutzfeldt-Jakob disease. Can a new subentity be recognized in man?,"One case of CJD with severe involvement of the white matter is discussed. The patient was admitted after a 3-month clinical course with rapidly increasing mental deterioration, coma vigil-like state, myoclonic twitching of the limbs and of the facial muscles. The EEG showed the typical features of CJD. The first CT scan, performed 3 month after onset, revealed only a mild cortical and subcortical atrophy of the brain. The second CT scan, 12 months later, showed a considerable cortical and subcortical atrophy of the brain. The patient died 18 months after onset. Neuropathological examination showed a severe degeneration in the gray matter, with spongiosis, loss of neurones and hypertrophic glial reaction. The white matter was also involved with severe spongiosis, demyelination and hypertrophic glial proliferation. The case is discussed in relation to the data in the literature. It is argued that cases of CJD with severe involvement of the white matter should be classified as a new neuropathological subentity of CJD.",myelin;age;autopsy;case report;central nervous system;computer analysis;computer assisted tomography;Creutzfeldt Jakob disease;dementia;diagnosis;electroencephalography;histology;human;muscle;myoclonus,"Macchi, G.;Abbamondi, A. L.;Di Trapani, G.;Sbriccoli, A.",1984,,,0,
2755,[Sneddon's syndrome: 15 cases with cerebral angiography] Le syndrome de Sneddon: etude de 15 cas avec arteriographie cerebrale,"Sneddon's syndrome is a rare disease defined by the presence of ischemic cerebrovascular events associated with livedo reticularis. We report a retrospective study of fifteen cases, thirteen women and two men, mean age of 37.93+/-9.77 years. All patients presented one or more cerebral infarcts. Six patients had dementia. Brain magnetic resonance imaging showed several cortical infarcts with white matter involvement. Cerebral angiography performed in all patients, showed a distal arteriopathy in twelve and thrombosis of the right carotid internal artery in one. One patient had antiphospholipid antibodies. Ten patients were treated with antiplatelet agents and five with anticoagulants. The course was favorable in eight patients and stationary in three. Four patients had several recurrent infarcts, one when anticoagulants were discontinued, one taking an anti-sludge-platelet agent and two who were not initially taking any treatment.","0 (Antibodies, Antiphospholipid);0 (Anticoagulants);0 (Platelet Aggregation Inhibitors);Adult;Antibodies, Antiphospholipid/analysis;Anticoagulants/therapeutic use;Carotid Artery, Internal/pathology;Cerebral Angiography;Cerebral Infarction/etiology/pathology/prevention & control;Dementia/etiology;Female;Humans;Intracranial Thrombosis/etiology/pathology/prevention & control;Magnetic Resonance Angiography;Male;Middle Aged;Platelet Aggregation Inhibitors/therapeutic use;Recurrence;Retrospective Studies;Sneddon Syndrome/drug therapy/ pathology/psychology","Maamar, M.;Rahmani, M.;Aidi, S.;Benabdeljlil, M.;El Hassani My, R.;Jiddane, M.;Hicham, Ch;El Alaoui-Faris, M.",2007,Sep,,0,
2756,Sneddon's syndrome: 15 cases with cerebral angiography,"Sneddon's syndrome is a rare disease defined by the presence of ischemic cerebrovascular events associated with livedo reticularis. We report a retrospective study of fifteen cases, thirteen women and two men, mean age of 37.93+/-9.77 years. All patients presented one or more cerebral infarcts. Six patients had dementia. Brain magnetic resonance imaging showed several cortical infarcts with white matter involvement. Cerebral angiography performed in all patients, showed a distal arteriopathy in twelve and thrombosis of the right carotid internal artery in one. One patient had antiphospholipid antibodies. Ten patients were treated with antiplatelet agents and five with anticoagulants. The course was favorable in eight patients and stationary in three. Four patients had several recurrent infarcts, one when anticoagulants were discontinued, one taking an anti-sludge-platelet agent and two who were not initially taking any treatment.","Adult;Antibodies, Antiphospholipid/analysis;Anticoagulants/therapeutic use;Carotid Artery, Internal/pathology;Cerebral Angiography;Cerebral Infarction/etiology/pathology/prevention & control;Dementia/etiology;Female;Humans;Intracranial Thrombosis/etiology/pathology/prevention & control;Magnetic Resonance Angiography;Male;Middle Aged;Platelet Aggregation Inhibitors/therapeutic use;Recurrence;Retrospective Studies;Sneddon Syndrome/drug therapy/ pathology/psychology","Maamar, M.;Rahmani, M.;Aidi, S.;Benabdeljlil, M.;El Hassani My, R.;Jiddane, M.;Hicham, C.;El Alaoui-Faris, M.",2007,Sep,,0,
2757,"Binswanger's disease in the absence of chronic arterial hypertension. A case report with clinical, radiological and immunohistochemical observations on intracerebral blood vessels","The cerebral changes are described in a woman of 54 who suffered from Binswanger's encephalopathy; there were no signs or symptoms of chronic arterial hypertension. The disease presented as dementia of about 3 years duration. Computed tomography of the brain 2.5 years before her death showed bilateral widespread hypodense lesions in the cerebral white matter. She died of an asthmatic attack. Autopsy disclosed extensive bilateral degeneration of the central white matter, lacunes and gliosis. Severe obliterative arteriolosclerosis occurred in the meningeal vessels and those supplying the affected parts of the brain. Light microscopy showed that the most severe lesions occurred in the arterioles. Immunohistochemistry demonstrated profound extravasation of plasma proteins chiefly albumin, indicating dysfunction of the blood-brain barrier. Thus the lesions characteristic of Binswanger's encephalopathy may develop in the absence of chronic arterial hypertension. Additional pathogenic factors, possibly genetic predisposition to vascular injury may play a role in the development of this condition.",albumin;plasma protein;adult;arteriolosclerosis;article;autopsy;Binswanger encephalopathy;blood brain barrier;brain blood vessel;brain disease;brain injury;case report;computer assisted tomography;dementia;extravasation;female;histopathology;human;hypertension;immunohistochemistry;microscopy;nerve degeneration;neuropathology;priority journal;white matter,"Ma, K. C.;Lundberg, P. O.;Lilja, A.;Olsson, Y.",1992,,,0,
2758,Disrupted Brain Structural Connectivity: Pathological Interactions Between Genetic APOE ε4 Status and Developed MCI Condition,"The ε4 allele of the apolipoprotein E (APOE) gene and mild cognitive impairment (MCI) are both risk factors for Alzheimer’s disease (AD). One factor is genetic, and the other is a developed condition during the aging process. The current study intended to discover the interactions of these two factors, which may be useful in the construction of a sensitive biomarker for early identification and intervention. Eight hundred eighty-five Chinese Han ethnic subjects (aged 55 and older) completed neuropsychological tests and APOE genotyping. One hundred ten of these participants underwent magnetic resonance imaging (MRI) for T1 structural and diffusion tensor imaging scans. Subjects were divided into four groups according to APOE ε4 carrying status and MCI condition: ε4+ MCI, ε4+ normal cognition (NC), ε4− MCI, and ε4− NC. In the studied Han population in Beijing, 16.9 % (ε2ε4 = 1.1 %, ε3ε4 = 14.8 %, and ε4ε4 = 0.9 %) carried at least one ε4 allele. Significant interactions between APOE ε4 and MCI were found in general cognitive function (p = 0.001) and white matter connectivity network (clustering coefficient, p = 0.004, and local efficiency, p = 0.011); the combination of ε4 positivity and MCI was accompanied by reductions in Mini-Mental Status Examination (MMSE) scores, global white matter network connectivity, and the right hippocampus (rHIP) nodal efficiency within that network (false discovery rate (FDR), p < 0.05). Our results suggest the presence of a genetic risk and MCI led to more severe pathological symptoms and could be informative in the implementation of clinical trials for early stages of AD.",apolipoprotein E4;adult;aged;article;China;cognition;controlled study;cross-sectional study;diffusion tensor imaging;female;genotype;Han Chinese;hippocampus;human;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;nerve cell network;neuropsychological test;nuclear magnetic resonance imaging;pathogenesis;white matter,"Ma, C.;Wang, J.;Zhang, J.;Chen, K.;Li, X.;Shu, N.;Chen, Y.;Liu, Z.;Zhang, Z.",2017,,10.1007/s12035-016-0224-5,0,2759
2759,Disrupted Brain Structural Connectivity: Pathological Interactions Between Genetic APOE ε4 Status and Developed MCI Condition,"The ε4 allele of the apolipoprotein E (APOE) gene and mild cognitive impairment (MCI) are both risk factors for Alzheimer’s disease (AD). One factor is genetic, and the other is a developed condition during the aging process. The current study intended to discover the interactions of these two factors, which may be useful in the construction of a sensitive biomarker for early identification and intervention. Eight hundred eighty-five Chinese Han ethnic subjects (aged 55 and older) completed neuropsychological tests and APOE genotyping. One hundred ten of these participants underwent magnetic resonance imaging (MRI) for T1 structural and diffusion tensor imaging scans. Subjects were divided into four groups according to APOE ε4 carrying status and MCI condition: ε4+ MCI, ε4+ normal cognition (NC), ε4− MCI, and ε4− NC. In the studied Han population in Beijing, 16.9 % (ε2ε4 = 1.1 %, ε3ε4 = 14.8 %, and ε4ε4 = 0.9 %) carried at least one ε4 allele. Significant interactions between APOE ε4 and MCI were found in general cognitive function (p = 0.001) and white matter connectivity network (clustering coefficient, p = 0.004, and local efficiency, p = 0.011); the combination of ε4 positivity and MCI was accompanied by reductions in Mini-Mental Status Examination (MMSE) scores, global white matter network connectivity, and the right hippocampus (rHIP) nodal efficiency within that network (false discovery rate (FDR), p < 0.05). Our results suggest the presence of a genetic risk and MCI led to more severe pathological symptoms and could be informative in the implementation of clinical trials for early stages of AD.",adult;allele;China;clinical trial;cognition;controlled study;diffusion tensor imaging;disease carrier;gene disruption;genetic risk;genotype;human;major clinical study;mental health;middle aged;mild cognitive impairment;neuropsychological test;right hippocampus;symptom;white matter;apolipoprotein E;biological marker;endogenous compound,"Ma, C.;Wang, J.;Zhang, J.;Chen, K.;Li, X.;Shu, N.;Chen, Y.;Liu, Z.;Zhang, Z.",2016,,10.1007/s12035-016-0224-5,0,
2760,Focal Macroscopic Cortical Lesions in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy,"BACKGROUND AND PURPOSE: Cortical microinfarcts and secondary cortical degeneration have been demonstrated in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a severe monogenic cerebral small vessel disease. The aim of this study was to determine whether focal macroscopic cortical lesions can be detected using a specific in vivo magnetic resonance imaging approach. METHODS: Three-dimensional T1 magnetic resonance imaging scans were obtained in 28 nondemented nondisabled CADASIL patients and 29 age- and sex-matched controls. The cortical mantle of patients and controls were extracted using Brainvisa by an experienced user and then evaluated during a dedicated reading session by a second reader after removing the white matter to stay blind to the clinical status. Thereafter, confirmed focal macroscopic cortical lesions were characterized using all available imaging data, including 7-T magnetic resonance imaging in some patients. RESULTS: Three focal macroscopic cortical lesions were confirmed in 3 of 28 patients (11%) but none in controls. All lesions were observed in the close vicinity of severe signal changes in the underlying white matter. CONCLUSIONS: Focal macroscopic cortical lesions can be detected using specific magnetic resonance imaging approaches in CADASIL patients long before the end stage of the disorder. The underlying mechanisms and precise clinical consequences of these cortical changes still need to be determined.",Adult;Aged;CADASIL/ diagnostic imaging;Cerebral Cortex/ diagnostic imaging;Cohort Studies;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Cadasil;cerebral cortex;cerebral small vessel disease;subcortical ischemic vascular dementia;white matter,"Lyoubi-Idrissi, A.;De Guio, F.;Chabriat, H.;Jouvent, E.",2017,May,,0,2761
2761,Focal Macroscopic Cortical Lesions in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy,"BACKGROUND AND PURPOSE: Cortical microinfarcts and secondary cortical degeneration have been demonstrated in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a severe monogenic cerebral small vessel disease. The aim of this study was to determine whether focal macroscopic cortical lesions can be detected using a specific in vivo magnetic resonance imaging approach. METHODS: Three-dimensional T1 magnetic resonance imaging scans were obtained in 28 nondemented nondisabled CADASIL patients and 29 age- and sex-matched controls. The cortical mantle of patients and controls were extracted using Brainvisa by an experienced user and then evaluated during a dedicated reading session by a second reader after removing the white matter to stay blind to the clinical status. Thereafter, confirmed focal macroscopic cortical lesions were characterized using all available imaging data, including 7-T magnetic resonance imaging in some patients. RESULTS: Three focal macroscopic cortical lesions were confirmed in 3 of 28 patients (11%) but none in controls. All lesions were observed in the close vicinity of severe signal changes in the underlying white matter. CONCLUSIONS: Focal macroscopic cortical lesions can be detected using specific magnetic resonance imaging approaches in CADASIL patients long before the end stage of the disorder. The underlying mechanisms and precise clinical consequences of these cortical changes still need to be determined.",Cadasil;cerebral cortex;cerebral small vessel disease;subcortical ischemic vascular dementia;white matter,"Lyoubi-Idrissi, A.;De Guio, F.;Chabriat, H.;Jouvent, E.",2017,Mar 27,,0,
2762,Regional atrophy of the corpus callosum in subjects with Alzheimer's disease and multi-infarct dementia,"Regional areas of the corpus callosum (CC) were evaluated in subjects with dementia. The area of the CC and seven distinct subdivisions were measured in subjects with Alzheimer's disease (AD) (n = 162), multi-infarct dementia (MID) (n = 28), and in a healthy comparison group (n = 36). There were significant differences in the regional areas of the CC for both the AD and MID patients relative to values for the comparison subjects. When mildly demented (MMSE > or = 21), subjects with AD had significantly smaller posterior midbody, isthmus, and splenium and subjects with MID had significantly smaller genu relative to comparison subjects. This study reports different patterns of regional CC area loss in subjects with AD and MID.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis;Atrophy;Brain Mapping;Corpus Callosum/*pathology;Dementia, Multi-Infarct/*diagnosis;Diagnosis, Differential;Female;Humans;*Magnetic Resonance Imaging;Male;Neuropsychological Tests","Lyoo, I. K.;Satlin, A.;Lee, C. K.;Renshaw, P. F.",1997,May 16,,0,
2763,Central nervous system involvement in the eosinophilia-myalgia syndrome,"A patient with eosinophilia-myalgia syndrome developed progressive central nervous system involvement that did not improve despite discontinuation of L- tryptophan therapy. Neurologic impairment was manifested initially by spastic monoparesis, which was improved by treatment with methylprednisolone and hydroxyurea. Recurrence of weakness was accompanied by gait ataxia, dysphagia, and complaints of a gradual decline in memory and concentration. Neuropsychological testing identified a broad pattern of cognitive deficits suggestive of a subcortical dementia, and magnetic resonance imaging demonstrated multiple high-signal lesions in the white matter. Cognitive deficits appear to be underrecognized in patients with the eosinophilia- myalgia syndrome. The response of our patient's initial symptoms to corticosteroid therapy suggests a possible role for autoimmune mechanisms in the pathogenesis of central nervous system involvement in the eosinophilia- myalgia syndrome. Neuropsychological evaluation should be performed in patients with cognitive complaints to delineate the full spectrum of central nervous system impairment associated with the eosinophilia-myalgia syndrome.",,"Lynn, J.;Rammohan, K. W.;Bornstein, R. A.;Kissel, J. T.",1992,1992,,0,
2764,Clinical and genetic characterization of leukoencephalopathies in adults,"Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.","Adolescent;Adult;Exome/ genetics;Female;Genetic Predisposition to Disease/ genetics;Humans;Leukoencephalopathies/ diagnosis/ genetics;Male;Mutation;Sequence Analysis, DNA;Young Adult;imaging;leukodystrophy;neurodegeneration;white matter lesion","Lynch, D. S.;Rodrigues Brandao de Paiva, A.;Zhang, W. J.;Bugiardini, E.;Freua, F.;Tavares Lucato, L.;Macedo-Souza, L. I.;Lakshmanan, R.;Kinsella, J. A.;Merwick, A.;Rossor, A. M.;Bajaj, N.;Herron, B.;McMonagle, P.;Morrison, P. J.;Hughes, D.;Pittman, A.;Laura, M.;Reilly, M. M.;Warren, J. D.;Mummery, C. J.;Schott, J. M.;Adams, M.;Fox, N. C.;Murphy, E.;Davagnanam, I.;Kok, F.;Chataway, J.;Houlden, H.",2017,May 1,,0,
2765,Clinical and genetic characterization of leukoencephalopathies in adults,"Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.",imaging;leukodystrophy;neurodegeneration;white matter lesion,"Lynch, D. S.;Rodrigues Brandao de Paiva, A.;Zhang, W. J.;Bugiardini, E.;Freua, F.;Tavares Lucato, L.;Macedo-Souza, L. I.;Lakshmanan, R.;Kinsella, J. A.;Merwick, A.;Rossor, A. M.;Bajaj, N.;Herron, B.;McMonagle, P.;Morrison, P. J.;Hughes, D.;Pittman, A.;Laura, M.;Reilly, M. M.;Warren, J. D.;Mummery, C. J.;Schott, J. M.;Adams, M.;Fox, N. C.;Murphy, E.;Davagnanam, I.;Kok, F.;Chataway, J.;Houlden, H.",2017,Mar 02,,0,2764
2766,[Binswanger's disease--diagnostic criteria and analysis of cases] Choroba binswangera--kryteria diagnostyczne i analiza przypadkow,"Binswanger's disease(BD) in an effect of a vascular destruction of deep white matter structures following multiple infarcts leading to disturbances of perception functions, recent memory and characterological disorders. BD is a disease occurring in late 6th decade of life. Computerized tomography and magnetic resonance imaging demonstrate foci of microinfarcts which coexist with arterial hypertension, atheromatous lesions and general cerebral atherosclerosis. BD leads to dementia, certain Parkinson-like signs, pyramidal system involvement, depression, organic brain damage syndrome, dysbasia and sphincter control loss. Ten patients observed by the author are reported.","Aged;Dementia, Vascular/ diagnosis;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Lyczak, P.;Magdziak, J.;Galubinski, A.;Malczewski, P.",1999,,,0,
2767,Binswanger's disease--diagnostic criteria and analysis of cases,"Binswanger's disease(BD) in an effect of a vascular destruction of deep white matter structures following multiple infarcts leading to disturbances of perception functions, recent memory and characterological disorders. BD is a disease occurring in late 6th decade of life. Computerized tomography and magnetic resonance imaging demonstrate foci of microinfarcts which coexist with arterial hypertension, atheromatous lesions and general cerebral atherosclerosis. BD leads to dementia, certain Parkinson-like signs, pyramidal system involvement, depression, organic brain damage syndrome, dysbasia and sphincter control loss. Ten patients observed by the author are reported.","Aged;Dementia, Vascular/ diagnosis;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Lyczak, P.;Magdziak, J.;Galubinski, A.;Malczewski, P.",1999,,,0,
2768,"APOE/TOMM40 genetic loci, white matter hyperintensities, and cerebral microbleeds","Background: Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease.Aim and/or hypothesis: To test for independent associations between two Alzheimer's disease-susceptibility gene loci - APOE ε and the TOMM40 '523' poly-T repeat - and white matter hyperintensities/cerebral microbleed burden in community-dwelling older adults.Methods: Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 07; range = 71-74).Results: No significant effects of APOE ε or TOMM40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants.Conclusions: Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature.",,"Lyall, D. M.;Maniega, S. M.;Harris, S. E.;Bastin, M. E.;Murray, C.;Lutz, M. W.;Saunders, A. M.;Roses, A. D.;Hernández, M. C. V.;Royle, N. A.;Starr, J. M.;Porteous, D. J.;Deary, I. J.;Wardlaw, J. M.",2015,1,,0,
2769,Are APOE varepsilon genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?,"Genetic polymorphisms in the APOE varepsilon and TOMM40 '523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE varepsilon2/varepsilon3/varepsilon4 status and TOMM40 523 poly-T repeat length. Data were available from 758-814 subjects for cognitive analysis, and 522-543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations--particularly those related to tests of information processing speed--were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.","Aged;Aging/genetics/physiology;Apolipoproteins E/ genetics;Cognition Disorders/ genetics;Diffusion Tensor Imaging;Female;Gene Frequency/genetics;Humans;Male;Neuropsychological Tests;Poly T/ genetics;Polymorphism, Genetic/ genetics;White Matter/ physiology","Lyall, D. M.;Harris, S. E.;Bastin, M. E.;Munoz Maniega, S.;Murray, C.;Lutz, M. W.;Saunders, A. M.;Roses, A. D.;Valdes Hernandez Mdel, C.;Royle, N. A.;Starr, J. M.;Porteous, D. J.;Wardlaw, J. M.;Deary, I. J.",2014,,10.1038/tp.2014.89,0,
2770,"Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936","Apolipoprotein E (APOE) ε genotype has previously been significantly associated with cognitive, brain imaging, and Alzheimer's disease-related phenotypes (e.g., age of onset). In the TOMM40 gene, the rs10524523 (""523"") variable length poly-T repeat polymorphism has more recently been associated with similar ph/enotypes, although the allelic directions of these associations have varied between initial reports. Using diffusion magnetic resonance imaging tractography, the present study aimed to investigate whether there are independent effects of apolipoprotein E (APOE) and TOMM40 genotypes on human brain white matter integrity in a community-dwelling sample of older adults, the Lothian Birth Cohort 1936 (mean age= 72.70years, standard deviation= 0.74, N approximately= 640-650; for most analyses). Some nominally significant effects were observed (i.e., covariate-adjusted differences between genotype groups at p < 0.05). For APOE, deleterious effects of ε4 ""risk"" allele presence (vs. absence) were found in the right ventral cingulum and left inferior longitudinal fasciculus. To test for biologically independent effects of the TOMM40 523 repeat, participants were stratified into APOE genotype subgroups, so that any significant effects could not be attributed to APOE variation. In participants with the APOE ε3/ε4 genotype, effects of TOMM40 523 status were found in the left uncinate fasciculus, left rostral cingulum, left ventral cingulum, and a general factor of white matter integrity. In all 4 of these tractography measures, carriers of the TOMM40 523 ""short"" allele showed lower white matter integrity when compared with carriers of the ""long"" and ""very-long"" alleles. Most of these effects survived correction for childhood intelligence test scores and vascular disease history, though only the effect of TOMM40 523 on the left ventral cingulum integrity survived correction for false discovery rate. The effects of APOE in this older population are more specific and restricted compared with those reported in previous studies, and the effects of TOMM40 on white matter integrity appear to be novel, although replication is required in large independent samples. © 2014 The Authors.",,"Lyall, D. M.;Harris, S. E.;Bastin, M. E.;Muñoz Maniega, S.;Murray, C.;Lutz, M. W.;Saunders, A. M.;Roses, A. D.;Valdés Hernández, M. D. C.;Royle, N. A.;Starr, J. M.;Porteous, D. J.;Wardlaw, J. M.;Deary, I. J.",2014,June,,0,
2771,Are APOE ε genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?,"Genetic polymorphisms in the APOE ε and TOMM40 '523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d. = 0.74). Participants were genotyped for APOE ε2/ε3/ε4 status and TOMM40 523 poly-T repeat length. Data were available from 758-814 subjects for cognitive analysis, and 522-543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values allo0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOEcognitive ageing associations-particularly those related to tests of information processing speed-were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.",,"Lyall, D. M.;Harris, S. E.;Bastin, M. E.;Muñoz Maniega, S.;Murray, C.;Lutz, M. W.;Saunders, A. M.;Roses, A. D.;Del, C. V. H. M.;Royle, N. A.;Starr, J. M.;Porteous, D. J.;Wardlaw, J. M.;Deary, I. J.",2014,,,0,
2772,Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition,"OBJECTIVES: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. METHODS: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. RESULTS: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. CONCLUSIONS: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191-204).",,"Ly, M.;Adluru, N.;Destiche, D. J.;Lu, S. Y.;Oh, J. M.;Hoscheidt, S. M.;Alexander, A. L.;Okonkwo, O. C.;Rowley, H. A.;Sager, M. A.;Johnson, S. C.;Bendlin, B. B.",2016,Feb,10.1017/s1355617715001216,0,
2773,Brain microvascular injury and white matter disease provoked by diabetes-associated hyperamylinemia,"OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins. METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses of human brain tissues and studied the effects of the aggregated amylin on endothelial cells ex vivo. RESULTS: Amylin deposition in brain blood vessels is associated with vessel wall disruption and abnormal surrounding neuropil in patients with type 2 diabetes and dementia, in HIP rats, and in AKO rats infused with aggregated amylin. HIP rats have brain microhemorrhages, white matter injury, and neurologic deficits. Vascular amylin deposition provokes loss of endothelial cell coverage and tight junctions. Intravenous infusion in AKO rats of human amylin, or combined human amylin and apolipoprotein E4, showed that amylin binds to plasma apolipoproteins. The intravenous infusion of apolipoprotein E4 exacerbated the brain accumulation of aggregated amylin and vascular pathology in HIP rats. INTERPRETATION: These data identify vascular amylin deposition as a trigger of brain endothelial dysfunction that is modulated by plasma apolipoproteins and represents a potential therapeutic target in diabetes-associated dementia and stroke. Ann Neurol 2017;82:208-222.","0 (Apolipoprotein E4);0 (Islet Amyloid Polypeptide);Aged, 80 and over;Animals;Apolipoprotein E4/administration & dosage/adverse effects;Brain/blood supply/drug effects/ pathology;Cells, Cultured;Diabetes Mellitus, Type 2/blood/complications/ pathology;Drug Synergism;Endothelium/metabolism;Gene Knockout Techniques;Humans;Intracranial Hemorrhages/chemically induced;Islet Amyloid Polypeptide/ adverse effects/blood/metabolism;Leukoencephalopathies/blood/ chemically induced/complications/ pathology;Magnetic Resonance Imaging;Maze Learning/drug effects;Microvessels/ metabolism;Motor Skills/drug effects;Neuroimaging;Pancreas/metabolism;Rats;Rats, Mutant Strains;Tight Junctions/drug effects","Ly, H.;Verma, N.;Wu, F.;Liu, M.;Saatman, K. E.;Nelson, P. T.;Slevin, J. T.;Goldstein, L. B.;Biessels, G. J.;Despa, F.",2017,Aug,,0,
2774,"Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer's Disease: The Atherosclerosis Risk in Communities Study (ARIC)","BACKGROUND: A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. OBJECTIVE: We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years. METHODS: Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (>/=15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, >/=8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. RESULTS: At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. CONCLUSIONS: In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.",,"Lutsey, P. L.;Norby, F. L.;Gottesman, R. F.;Mosley, T.;MacLehose, R. F.;Punjabi, N. M.;Shahar, E.;Jack, C. R., Jr.;Alonso, A.",2016,,10.1371/journal.pone.0158758,0,
2775,Single-index varying coefficient model for functional responses,"Recently, massive functional data have been widely collected over space across a set of grid points in various imaging studies. It is interesting to correlate functional data with various clinical variables, such as age and gender, in order to address scientific questions of interest. The aim of this article is to develop a single-index varying coefficient (SIVC) model for establishing a varying association between functional responses (e.g., image) and a set of covariates. It enjoys several unique features of both varying-coefficient and single-index models. An estimation procedure is developed to estimate varying coefficient functions, the index function, and the covariance function of individual functions. The optimal integration of information across different grid points is systematically delineated and the asymptotic properties (e.g., consistency and convergence rate) of all estimators are examined. Simulation studies are conducted to assess the finite-sample performance of the proposed estimation procedure. Furthermore, our real data analysis of a white matter tract dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study confirms the advantage and accuracy of SIVC model over the popular varying coefficient model.","Alzheimer Disease/ diagnostic imaging;Computer Simulation;Humans;Models, Statistical;Neuroimaging/ statistics & numerical data;White Matter/diagnostic imaging;Functional response;Image analysis;Single index;Uniform convergence;Varying coefficient","Luo, X.;Zhu, L.;Zhu, H.",2016,Dec,,0,
2776,Single-index varying coefficient model for functional responses,"Recently, massive functional data have been widely collected over space across a set of grid points in various imaging studies. It is interesting to correlate functional data with various clinical variables, such as age and gender, in order to address scientific questions of interest. The aim of this article is to develop a single-index varying coefficient (SIVC) model for establishing a varying association between functional responses (e.g., image) and a set of covariates. It enjoys several unique features of both varying-coefficient and single-index models. An estimation procedure is developed to estimate varying coefficient functions, the index function, and the covariance function of individual functions. The optimal integration of information across different grid points is systematically delineated and the asymptotic properties (e.g., consistency and convergence rate) of all estimators are examined. Simulation studies are conducted to assess the finite-sample performance of the proposed estimation procedure. Furthermore, our real data analysis of a white matter tract dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study confirms the advantage and accuracy of SIVC model over the popular varying coefficient model.",,"Luo, X.;Zhu, L.;Zhu, H.",2016,Apr 8,10.1111/biom.12526,0,2775
2777,Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study,"APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE epsilon2 carriers, 54 APOE epsilon4 carriers and 90 epsilon3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson's correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with epsilon4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in epsilon4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson's correlation analysis showed parietal WMH volume was significantly related with IPS, especially in epsilon4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE epsilon4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in epsilon4 carriers, was independently contributed to slower IPS.",Apoe;Information processing speed;Surface-based analysis;Voxel-based morphometry (VBM);White matter hyperintensities,"Luo, X.;Jiaerken, Y.;Yu, X.;Huang, P.;Qiu, T.;Jia, Y.;Sun, J.;Zhou, J.;Zhang, M.;Alzheimer's Disease Neuroimaging, Initiative",2017,Aug,,0,
2778,Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study,"APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE epsilon2 carriers, 54 APOE epsilon4 carriers and 90 epsilon3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson's correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with epsilon4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in epsilon4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson's correlation analysis showed parietal WMH volume was significantly related with IPS, especially in epsilon4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE epsilon4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in epsilon4 carriers, was independently contributed to slower IPS.",Apoe;Information processing speed;Surface-based analysis;Voxel-based morphometry (VBM);White matter hyperintensities,"Luo, X.;Jiaerken, Y.;Yu, X.;Huang, P.;Qiu, T.;Jia, Y.;Sun, J.;Zhou, J.;Zhang, M.",2016,Jul 21,10.1007/s11682-016-9571-0,0,
2779,Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study,"OBJECTIVE: It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data. METHOD: There were 135 healthy elderly (including epsilon2, epsilon4 allele carriers and epsilon3 homozygotes) who had completed two years' follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer's disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD. RESULTS: We found that APOE epsilon4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE epsilon4 carriers had significantly decreased Abeta1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and epsilon4 allele was related with declining trend of cognition. CONCLUSION: Our findings suggested APOE epsilon4 allele was associated with increased Abeta deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and epsilon4 allele can exert long-term detrimental effects on individual's trajectory of cognition.",apolipoprotein E (APOE);cerebral small-vascular disease (CSVD);cognition;dilated perivascular space (dPVS);white matter hyperintensities (WMH),"Luo, X.;Jiaerken, Y.;Yu, X.;Huang, P.;Qiu, T.;Jia, Y.;Li, K.;Xu, X.;Shen, Z.;Guan, X.;Zhou, J.;Zhang, M.;Adni, Ftadni",2017,Jul 4,,0,
2780,Alteration of regional homogeneity and white matter hyperintensities in amnestic mild cognitive impairment subtypes are related to cognition and CSF biomarkers,"Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Abeta level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.",Alzheimer's disease;Csf;Cognition;Magnetic resonance imaging;Mild cognitive impairment;Precuneus;White matter hyperintensities,"Luo, X.;Jiaerken, Y.;Huang, P.;Xu, X. J.;Qiu, T.;Jia, Y.;Shen, Z.;Guan, X.;Zhou, J.;Zhang, M.;Alzheimer's Disease Neuroimaging, Initiative",2017,Feb 24,,0,
2781,Heritability of magnetic resonance imaging (MRI) traits in Alzheimer disease cases and their siblings in the MIRAGE study,"Magnetic resonance imaging (MRI) traits can serve as more specific measures of degenerative or cerebrovascular brain injury than can be ascertained through personal history, risk factors, clinical signs, or symptoms. They are potentially useful intermediate phenotypes for genetic studies of Alzheimer disease (AD). Recent studies have estimated heritability of white matter hyperintensity (WMH) among cognitively normal family members to be between 0.55 and 0.73. Persons discordant for AD are expected to have substantially different MRI phenotype distributions; our goal was to determine whether MRI traits in siblings discordant for AD are heritable. We measured cerebral atrophy, medial temporal atrophy (MTA), WMH, and a rating of cerebrovascular disease (CVR) via MRI in 815 participants from 424 families of the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study. Residual heritability after adjustment for covariates ranged from 0.17 (P=0.009) for MTA to 0.57 (P=10) for CVR. The number of APOE-ε4 alleles was significantly associated with WMH (P=0.01) and CVR (P=0.005) but not cerebral atrophy (P=0.25) or MTA (P=0.83). Heritability remained significant and high after adjusting for APOE genotype, suggesting that a substantial proportion of the additive genetic variation in these MRI traits is explained by other genes. In the Multi-Institutional Research in Alzheime's Genetic Epidemiology Study of AD-discordant siblings, MRI traits are heritable and are potential endophenotypes for genetic association studies. © 2007 Lippincott Williams & Wilkins, Inc.",,"Lunetta, K. L.;Erlich, P. M.;Cuenco, K. T.;Adrienne Cupples, L.;Green, R. C.;Farrer, L. A.;DeCarli, C.",2007,April/June,,0,
2782,Mice carrying a R142C Notch 3 knock-in mutation do not develop a CADASIL-like phenotype,"CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, MIM 125310) is a genetic vascular dementia disease that is linked to missense mutations, small in-frame deletions, and splice site mutations in the human Notch 3 gene. Here we describe the generation of a mouse knockin model for one of the most prevalent CADASIL mutations, an arginine to cysteine transition at position 141, R141C, which corresponds to mutation R142C in mouse NOTCH 3. CADASIL(R142C) mice show no apparent CADASIL-like phenotype after histological and MRI analysis. The NOTCH 3 (R142C) receptor is processed normally and does not appear to accumulate the ectodomain, which has been observed in CADASIL patients. We discuss possible reasons for the different outcomes of the same germline CADASIL mutation in mice and humans.","*Amino Acid Substitution;Animals;Aorta, Thoracic/pathology/ultrastructure;Behavior, Animal;Blotting, Western;CADASIL/*genetics;Carotid Artery, Common/pathology/ultrastructure;Cysteine/metabolism;Germ-Line Mutation;Magnetic Resonance Imaging;Male;Mice;Mice, Mutant Strains;*Phenotype;Polymerase Chain Reaction;Proto-Oncogene Proteins/*genetics;Receptors, Cell Surface/*genetics;Receptors, Notch;Sequence Analysis, DNA;Thoracic Vertebrae/ultrasonography","Lundkvist, J.;Zhu, S.;Hansson, E. M.;Schweinhardt, P.;Miao, Q.;Beatus, P.;Dannaeus, K.;Karlstrom, H.;Johansson, C. B.;Viitanen, M.;Rozell, B.;Spenger, C.;Mohammed, A.;Kalimo, H.;Lendahl, U.",2005,Jan,10.1002/gene.20091,0,
2783,"Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI","OBJECTIVES: To assess functional changes measured by cerebral blood flow (CBF) in the presymptomatic stage of frontotemporal dementia linked to chromosome 3 (FTD-3) caused by a truncating mutation in CHMP2B. DESIGN: Case-control study. SETTING: A memory clinic and tertiary referrals centre for dementia and inherited neurodegenerative disorders. PARTICIPANTS: The authors included 11 presymptomatic CHMP2B mutation carriers and seven first-degree-related family non-carriers. Participants were MRI scanned twice with an interval of 15 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Local functional changes in brain tissue perfusion were measured as CBF with two different MR techniques, gradient echo (GRE) and spin echo (SE), focusing on CBF in all cerebral vessels (GRE) and cerebral capillaries (SE), respectively. As planned, data analysis included co-registration of perfusion images to structural T1 images. Perfusion data were then extracted from seven regions-of-interest, normalised to white matter and statistically compared between carriers and non-carriers. RESULTS: For SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus. There was no evidence of changes from baseline to follow-up. For GRE, there were no significant differences between carriers and non-carriers. CONCLUSIONS: Significantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes. Comparing SE with GRE, data indicate that FTD-3 vascular pathology might primarily affect brain capillaries.",,"Lunau, L.;Mouridsen, K.;Rodell, A.;Ostergaard, L.;Nielsen, J. E.;Isaacs, A.;Johannsen, P.",2012,,10.1136/bmjopen-2011-000368,0,
2784,"Effects of CT-localized scalp round-needling on the blood rheology, NO and NOS of patients with multiple infarctional dementia","OBJECTIVE: To observe the short-term therapeutic effects of CT-localized scalp round-needling on the blood rheology, nitric oxide (NO) and nitric oxide synthetase (NOS) of patients with multiple infarctional dementia. METHODS: 89 cases of multiple infarctional dementia were randomly divided into an electro-round-needling group (57 cases), and a western medication group (32 cases). The therapeutic effects, including the effects on the blood rheology, NO and NOS, were observed. RESULTS: After receiving same courses of treatment, both the electro-round-needling group and the western medication group showed significant differences in the various kinds of indexes (P < 0.05-0.01). CONCLUSION: The CT-localized scalp round-needling is an effective therapy for multiple infarctional dementia.","*Acupuncture Therapy;Aged;Dementia, Multi-Infarct/radiography/*therapy;Female;Humans;Male;Middle Aged;Nitric Oxide/*blood;Nitric Oxide Synthase/*blood;Rheology;Scalp/*radiography;Tomography, X-Ray Computed","Lun, X.;Yang, W.;Fu, B.",2006,Jun,,0,
2785,[Observation on efficacy of CT positioning scalp circum-needling combined with Chinese herbal medicine in treating poly-infarctional vascular dementia],"OBJECTIVE: To observe the short-term effect of patients with poly-infarctional vascular dementia (PIVD) treated by CT positioning scalp circum-needling (SCN) combined with Chinese herbal medicine. METHODS: Eighty-nine patients of PIVD were enrolled and divided into the treated group (n = 57) and the control group (n = 32). They were all treated with oral taking of Fuyuan mixture (FYM, consisted of ginseng, medlar, salvia, bitter cardamon, etc). To the treated group, SCN was applied additionally with the unilateral area around the reflecting region (localized by CT) in scalp as main needling points and Ganshu, Shenshu, Zusanli, Hegu as supplementary points. Two courses of SCN were performed. The changes of clinical symptoms, intelligence and hemorrheological characteristics in patients were analysed. RESULTS: After two courses of treatment, the total effective rate in the treated group was 96.5%, which was better than that in the control group (75.0%), with significant difference (u = 2.423, P < 0.01); HDS scores increased in both groups after treatment, showing significant difference as compared with that before treatment (P < 0.01), hemorrheologic parameters were also apparently improved. CONCLUSION: CT positioning SCN combined Chinese herbal medicine treatment has definite therapeutic effect in treating PIVD.","*Acupuncture Therapy/methods;Aged;Dementia, Multi-Infarct/radiography/*therapy;Drugs, Chinese Herbal/*therapeutic use;Electroacupuncture/methods;Female;Humans;Male;Middle Aged;*Phytotherapy;Scalp;Tomography, X-Ray Computed","Lun, X.;Rong, L.;Yang, W. H.",2003,Jun,,0,
2786,"Clinical spectrum, underlying etiologies and radiological characteristics of cortical superficial siderosis",Cortical superficial siderosis (cSS) is an increasingly recognized,,"Lummel, N.;Wollenweber, F. A.;Demaerel, P.;Bochmann, K.;Malik, R.;Opherk, C.;Linn, J.",2015,17,,0,
2787,Hyperattenuated intracerebral lesions after mechanical recanalization in acute stroke,"BACKGROUND AND PURPOSE: Following mechanical recanalization of an acute intracranial vessel occlusion, hyperattenuated lesions are frequently found on postinterventional cranial CT. They represent either blood or - more frequently - enhancement of contrast agent. Here, we aimed to evaluate the prognostic value of these hyperattenuated intracerebral lesions. MATERIALS AND METHODS: One hundred one consecutive patients with acute stroke in the anterior circulation who underwent mechanical recanalization were included. Risk factors for hyperattenuated intracerebral lesions were assessed, and lesion volume was compared with the volume of final infarction. Clinical outcome and relative risk of secondary hemorrhage were determined in patients with and without any hyperattenuated lesions and compared. RESULTS: The frequency of hyperattenuated lesions was 84.2%. Risk factors for hyperattenuated lesions were female sex, higher NIHSS score on admission, and higher amount of contrast agent applied. On follow-up, 3 patients showed no infarction; 53 patients, an ischemic infarction; and 45 patients, a hemorrhagic infarction. In all except 1 case, final volume of infarction (median = 92.4 mL) exceeded the volume of hyperattenuated intracerebral lesions (median = 5.6 mL). Patients with hyperattenuated lesions were at a 4 times higher relative risk for hemorrhagic transformation but had no significantly worse clinical outcome. CONCLUSIONS: Our data show that the extent of postinterventional hyperattenuated intracerebral lesions underestimates the volume of final infarction. Although hyperattenuated lesions indicate a higher risk of secondary hemorrhagic transformation, their presence seems not to be of any prognostic value regarding clinical outcome.",adult;aged;article;basal ganglion;bleeding;brain damage;brain hemorrhage;brain infarction size;brain ischemia;cerebrovascular accident;computed tomographic angiography;contrast enhancement;female;follow up;hemorrhagic transformation;hospital admission;human;major clinical study;male;mechanical thrombectomy;middle aged;National Institutes of Health Stroke Scale;nuclear magnetic resonance imaging;outcome assessment;prognosis;recanalization;risk factor;very elderly,"Lummel, N.;Schulte-Altedorneburg, G.;Bernau, C.;Pfefferkorn, T.;Patzig, M.;Janssen, H.;Opherk, C.;Brückmann, H.;Linn, J.",2014,,,0,
2788,"A misdiagnosed patient: 16 Years of locked-in syndrome, the influence of rehabilitation","Background: LiS can be mistakenly recognized as a vegetative state, minimally conscious state or akinetic mutism. It can be caused by isolated lesions - bilateral infarction, vertebrobasilar artery osslusion, haemorrhage or tumor of the ventral portion of the basis pontis or midbrain. Case Report: The case of a 65-year-old patient with a brain tumor localized in the posterior part of the posterior commissure of the brain was presented. He lost consciousness in 1991, was diagnosed as being at a terminal stage and from 2005 he started to improve. In MRI brain tumor stated in 1989 with the same localization and size in 2007 without any disturbance in cerebral fluid flow. The patients remained in this condition for 14 years without any rehabilitation, because he was diagnosed as a terminal stage, a non-operative stage. When exercises were introduced in 2005 the patient started to recover. In 2007 he was conscious with quadriplegia, a neuropsychological test showed memory problems, without any dementia. After intensive rehabilitation functional improvement and speech improvement was observed, GOS (4), Ranczo Los Amigos Scale (6), DRS (18). Conclusions: It is important to carry out full diagnostics before determining a terminal stage and to continue a rehabilitation program and multisensory stimulation. Even after 16 year of lying in bed without communication there is a chance in LiS to witness improvement after stimulation, without any signs of dementia. © Med Sci Monit, 2010.",aged;article;brain commissure;brain tumor;case report;cognitive therapy;diagnostic error;disease severity;human;locked in syndrome;male;memory disorder;music therapy;physiotherapy;quadriplegia;speech therapy;terminal disease;tumor localization;tumor volume;unconsciousness,"Lukowicz, M.;Matuszak, K.;Talar, A.",2010,,,0,
2789,Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia,"Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*psychology;Brain/blood supply/*pathology;Case-Control Studies;Cognition Disorders/*diagnosis/etiology;Dementia, Multi-Infarct/diagnosis/*psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Memory;Predictive Value of Tests;Psychiatric Status Rating Scales;Severity of Illness Index;Stroke/diagnosis/*psychology","Lukatela, K. A.;Cohen, R. A.;Kessler, H. A.;Jenkins, M. A.;Moser, D. J.;Stone, W. F.;Gordon, N. F.;Kaplan, R. F.",2000,Aug,10.1076/1380-3395(200008)22:4;1-0;ft445,0,
2790,Frontobasal gray matter loss is associated with the TREM2 p.R47H variant,"A rare heterozygous TREM2 variant p.R47H (rs75932628) has been associated with an increased risk for Alzheimer's disease (AD). We aimed to investigate the clinical presentation, neuropsychological profile, and regional pattern of gray matter and white matter loss associated with the TREM2 variant p.R47H, and to establish which regions best differentiate p.R47H carriers from noncarriers in 2 sample sets (Spanish and Alzheimer's Disease Neuroimaging Initiative, ADNI1). This was a cross-sectional study including a total number of 16 TREM2 p.R47H carriers diagnosed with AD or mild cognitive impairment, 75 AD p.R47H noncarriers and 75 cognitively intact TREM2 p.R47H noncarriers. Spanish AD TREM2 p.R47H carriers showed apraxia (9 of 9) and psychiatric symptoms such as personality changes, anxiety, paranoia, or fears more frequently than in AD noncarriers (corrected p = 0.039). For gray matter and white matter volumetric brain magnetic resonance imaging voxelwise analyses, we used statistical parametric mapping (SPM8) based on the General Linear Model. We used 3 different design matrices with a full factorial design. Voxel-based morphometry analyses were performed separately in the 2 sample sets. The absence of interset statistical differences allowed us to perform joint and conjunction analyses. Independent voxel-based morphometry analysis of the Spanish set as well as conjunction and joint analyses revealed substantial gray matter loss in orbitofrontal cortex and anterior cingulate cortex with relative preservation of parietal lobes in AD and/or mild cognitive impairment TREM2 p.R47H carriers, suggesting that TREM2 p.R47H variant is associated with certain clinical and neuroimaging AD features in addition to the increased TREM2 p.R47H atrophy in temporal lobes as described previously. The high frequency of pathologic behavioral symptoms, combined with a preferential frontobasal gray matter cortical loss, suggests that frontobasal and temporal regions could be more susceptible to the deleterious biological effects of the TREM2 variant p.R47H.","Aged;Aged, 80 and over;Alzheimer Disease/ genetics/ pathology;Cross-Sectional Studies;Female;Genetic Association Studies;Genetic Predisposition to Disease/genetics;Genetic Variation/ genetics;Gray Matter/ pathology;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Membrane Glycoproteins/ genetics;Middle Aged;Mild Cognitive Impairment/genetics/pathology;Neuroimaging;Receptors, Immunologic/ genetics;Risk","Luis, E. O.;Ortega-Cubero, S.;Lamet, I.;Razquin, C.;Cruchaga, C.;Benitez, B. A.;Lorenzo, E.;Irigoyen, J.;Pastor, M. A.;Pastor, P.",2014,Dec,10.1016/j.neurobiolaging.2014.06.007,0,
2791,Neuroimaging Correlates of Frontotemporal Dementia Associated with SQSTM1 Mutations,"BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD). OBJECTIVE: The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction. METHODS: We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n = 10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n = 20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n = 20). The groups were matched according to current age, disease duration, and gender. RESULTS: After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres. CONCLUSIONS: These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.",Dementia;SQSTM1 protein;frontotemporal dementia;voxel-based morphometry,"Luis, E.;Ortiz, A.;Eudave, L.;Ortega-Cubero, S.;Borroni, B.;van der Zee, J.;Gazzina, S.;Caroppo, P.;Rubino, E.;D'Agata, F.;Le Ber, I.;Santana, I.;Cunha, G.;Almeida, M. R.;Boutoleau-Bretonniere, C.;Hannequin, D.;Wallon, D.;Rainero, I.;Galimberti, D.;Van Broeckhoven, C.;Pastor, M. A.;Pastor, P.",2016,May 7,10.3233/jad-160006,0,
2792,Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease,"In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and association with neurodegeneration. A total of 88 patients with cognitive decline (54 mAD, 19 MCI, and 15 other dementias) were included in this study and compared with a group of younger (mean age, 31.3years) and older (mean age, 68.9years) healthy volunteers. Patients underwent detailed neurologic and neuropsychological examination, magnetic resonance imaging including voxel-based morphometry of gray matter, voxel-based diffusion tensor imaging, and white matter lesion volumetry, and PB and CSF analysis including multiparameter flow cytometry. Multiparameter flow cytometry revealed that proportions of activated HLA-DR positive CD4(+) and CD8(+) T-cells were slightly and significantly increased in the PB of MCI and mAD patients, respectively, when compared with healthy elderly controls but not in patients with other dementias. Although only a slight enhancement of the proportion of activated CD4(+) T-cells was observed in the CSF of both MCI and mAD patients, the proportion of activated CD8(+) T-cells was significantly increased in the CSF of mAD patients when compared with healthy elderly individuals. A slight increase in the proportion of activated CD8(+) T-cells was also observed in the intrathecal compartment of MCI patients. Activation of cytotoxic CD8(+) T-cells was considerably related to AD-typical neuropsychological deficits. Voxel-based regression analysis revealed a significant correlation between CD8(+) T-cell activation and microstructural tissue damage within parahippocampal areas as assessed by diffusion tensor imaging. Taken together, peripheral and intrathecal CD8(+) T-cell activation in mAD was significantly different from other dementias, suggesting a specific adaptive immune response. Lymphocyte activation seems to have a clinical impact because levels of activated CD8(+) T-cells were correlated with clinical and structural markers of AD pathology.",,"Lueg, G.;Gross, C. C.;Lohmann, H.;Johnen, A.;Kemmling, A.;Deppe, M.;Groger, J.;Minnerup, J.;Wiendl, H.;Meuth, S. G.;Duning, T.",2015,1,,0,
2793,Cranial computed tomography in disorders of complex carbohydrate metabolism and related storage diseases,"Computed tomography (CT) was performed on 34 children with different disorders of complex carbohydrate metabolism and related storage diseases to obtain data on the degree of cerebral involvement. The main findings on CT were cerebral atrophy and hypodensity of the white matter. There was a great variability in these CT findings, even in siblings. Among the patients there were several in whom CT was normal, so a negative study does not exclude one of these disorders. These findings show that CT features such as cerebral atrophy or hypodensity are helpful in the evaluation of these disorders, though a diagnosis cannot be made on the basis of CT alone.",oligosaccharide;article;child;computer assisted tomography;disorders of carbohydrate metabolism;human;lipidosis;metabolic encephalopathy;metabolism;mucolipidosis;mucopolysaccharidosis;neuronal ceroid lipofuscinosis;radiography,"Ludwig, B.;Kishikawa, T.;Wende, S.;Rochel, M.;Gehler, J.",1983,,,0,
2794,Searching for the philosopher's stone: Promising links between meditation and brain preservation,"Because of an aging population and increased prevalence of dementia and other neurodegenerative diseases, developing strategies to decrease the negative effects of aging are imperative. The scientific study of meditation as a potential tool to downregulate processes implicated in brain aging is an emerging field, and a growing body of research suggests that mindfulness practices are beneficial for cerebral resilience. Adding further evidence to this, an increasing number of imaging studies report effects of meditation on brain structure that are consistent with what is known about neuroprotection. Here, we review the published findings and address the question of whether meditation diminishes age-related brain degeneration. Although analyses are still sparse and based on cross-sectional data, study outcomes suggest that meditation might be beneficial for brain preservation-both with respect to gray and white matter-possibly by slowing down the natural (age-related) decrease of brain tissue. Until robust longitudinal data become available, however, a causal link between meditation and brain preservation cannot be made. Our discussion will also include a comprehensive commentary on the limitations of existing research and conclude with implications and directions for future studies.",aging;brain degeneration;human;human experiment;meditation;mindfulness;nuclear magnetic resonance imaging;white matter,"Luders, E.;Cherbuin, N.",2016,,10.1111/nyas.13082,0,2795
2795,Searching for the philosopher's stone: promising links between meditation and brain preservation,"In the context of an aging population and increased prevalence of dementia and other neurodegenerative diseases, developing strategies to decrease the negative effects of aging is imperative. The scientific study of meditation as a potential tool to downregulate processes implicated in brain aging is an emerging field, and a growing body of research suggests that mindfulness practices are beneficial for cerebral resilience. Adding further evidence to this notion, an increasing number of imaging studies report effects of meditation on brain structure that are consistent with our understanding of neuroprotection. Here, we review the published findings in this field of research addressing the question of whether meditation diminishes age-related brain degeneration. Altogether, although analyses are still sparse and based on cross-sectional data, study outcomes suggest that meditation might be beneficial for brain preservation-both with respect to gray and white matter-possibly by slowing down the natural (age-related) decrease of brain tissue. Nevertheless, it should also be recognized that, until robust longitudinal data become available, there is no evidence for causation between meditation and brain preservation. This review includes a comprehensive commentary on limitations of the existing research and concludes with implications and directions for future studies.",Mri;aging;brain;meditation;mindfulness,"Luders, E.;Cherbuin, N.",2016,Jun,10.1111/nyas.13082,0,
2796,Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging,"The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) was evaluated. Thirteen cognitively normal (CN) elderly subjects, 35 mostly amnestic MCI subjects and 20 subjects with mild probable AD were enrolled. During i.v. injection of gadopentetate dimeglumine, a dynamic T2*-weighted single-shot EPI sequence was conducted using a 1.5-T scanner. Frontobasal (FROB), temporoparietal (TPAR), mesiotemporal (MTMP), anterior and posterior cingular (ACING, PCING), amygdala (AMYG), thalamus and cerebellar brain regions were studied. rCBF was computed from regional cerebral blood volume and arterial input function and normalised to white matter. Images were analysed by manually placed regions of interest using anatomical coregistration. Significant decreases of rCBF were detected in MCI vs. CN in MTMP (-23%), AMYG (-20%) and ACING (-15%) with no further decline in mild AD. In PCING hypoperfusion (-10%) was confined to AD. These hypoperfusional changes are a possible correlate of localised impairment of CNS function. In FROB no perfusion changes were observed between diagnostic groups, but hyperperfusion was observed in mild dementia stages, possibly reflecting functional compensatory mechanisms. These data suggest that PW-MRI detects specific changes in rCBF not only in AD, but also in amnestic MCI, a disorder suggested to largely represent a pre-dementia stage of AD. This method may thus be useful in both research and clinical applications to detect early functional brain changes in the pathogenesis of dementias.",Aged;Alzheimer Disease/ physiopathology;Cerebrovascular Circulation;Dementia/ physiopathology;Female;Humans;Magnetic Resonance Angiography;Male;Middle Aged;Severity of Illness Index,"Luckhaus, C.;Flub, M. O.;Wittsack, H. J.;Grass-Kapanke, B.;Janner, M.;Khalili-Amiri, R.;Friedrich, W.;Supprian, T.;Gaebel, W.;Modder, U.;Cohnen, M.",2008,Apr 1,10.1016/j.neuroimage.2007.11.053,0,
2797,Stroke and alzheimer's disease: Shared mechanisms of vascular disruption,"Recent evidence suggests that Alzheimer's disease is a vascular disorder that can be accelerated by ischemic stroke. We propose that the underlying pathophysiology accelerating degenerative changes is due to blood brain barrier disruption following ischemia. A transient middle cerebral artery occlusion suture model was used in triple-transgenic AD mice and C57/Bl6 wild type controls. A separate triple-transgenic AD mice group was used for sham control. The middle cerebral artery was occluded for 1 hour followed by reperfusion. Mice were evaluated for sickness behavior and received a modified neurologic score. 5 hours after reperfusion, blood brain barrier tracers (Texas red, IcG, and AIB1) were injected i.v. into the femoral vein and allowed to circulate for 10 minutes. H&E, Cresyl Violet, and Thioflavin were used to stain sections of the brain for areas of degeneration. Images were obtained by quantitative fluorescent and bright-field microscopy. One-way ANOVA with Tukey's post-hoc comparison was used to compare between groups. P<0.05 was considered statistically significant. A statistically significant difference between groups was seen for blood brain barrier permeability following ischemia and reperfusion. Triple-transgenic AD mice had a 2-fold increase in Texas red and a 4-fold increase in AIB1 at 5 hours after reperfusion. No significant differences were seen in the control groups. H&E staining revealed nuclear fragmentation, chromatolysis, and vacuolization in the ipsilateral cortex of the triple-transgenic AD mice exposed to stroke. Limited areas of necrosis were seen in the C57/Bl6 controls. A significant increase in thioflavin staining was seen post-stroke in the triple-transgenic AD mice. The amyloid distribution was perivascular and significantly increased compared to the triple-transgenic AD sham mice. Triple-transgenic AD mice had a worse sickness score (avg. 13) compared to C57/Bl6 controls (avg. 17). Stroke and Alzheimer's disease share similar vascular mechanisms related to blood brain barrier disruption. We show that blood brain barrier disruption post-stroke accelerates degenerative changes. Targeting blood brain barrier disruption as a treatment approach may prove promising and warrants continued investigation.",cerebrovascular accident;cerebrovascular disease;ischemia;human;infarction;reperfusion;vascular disease;aged;American;heart;nursing;Alzheimer disease;mouse;blood brain barrier;United States;staining;brain ischemia;middle cerebral artery occlusion;post hoc analysis;permeability;necrosis;suture;model;bright field microscopy;degeneration;brain;femoral vein;pathophysiology;stain;illness behavior;middle cerebral artery;control group;cell vacuole;diseases;wild type;analysis of variance;indocyanine green;tracer;amyloid,"Lucke-Wold, B.;Logsdon, A.;Mohammad, A.;Adkins, C.;Ren, X.;Huber, J.;Rosen, C.;Simpkins, J.;Lockman, P.",2016,,,0,
2798,Subclinical cerebrovascular disease in mild cognitive impairment,"BACKGROUND: Cerebrovascular disease (CVD) may contribute to mild cognitive impairment (MCI). We sought to determine the relation of white matter hyperintensity (WMH) volume and infarcts in brain MRI to MCI in a community-based sample. METHODS: A total of 679 elderly persons without dementia underwent brain MRI. WMH and infarcts were quantified using research methods. WMH was adjusted for total cranial volume. The Petersen criteria were used to define MCI. MCI was further subclassified into amnestic and non-amnestic. We used logistic regression to relate WMH and infarcts to prevalent MCI. RESULTS: WMH were associated with amnestic MCI (odds ratio [OR] = 1.9; 95% confidence interval [CI] 1.1, 3.4) but not non-amnestic MCI (OR = 1.2; 95% CI 0.4, 1.6) after adjusting for age, gender, ethnic group, education, and APOE-epsilon4. Infarcts were more strongly associated with non-amnestic MCI (OR = 2.7; 95% CI 1.5, 4.8) than amnestic MCI (OR = 1.4; 95% CI 0.9, 2.3). In secondary analyses using continuous cognitive scores as outcomes, WMH, but not infarcts, were related to memory, while infarcts were more strongly related with non-amnestic domains. CONCLUSION: White matter hyperintensity (WMH) is more strongly related to amnestic mild cognitive impairment (MCI). Infarcts are more strongly related to non-amnestic MCI. The nature of WMH in amnestic MCI requires further study.","Aged;Aged, 80 and over;Cerebrovascular Disorders/*complications/*diagnosis/psychology;Cognition Disorders/*complications/*diagnosis/psychology;Cohort Studies;Cross-Sectional Studies;Female;Follow-Up Studies;Humans;Male;Neuropsychological Tests;Retrospective Studies","Luchsinger, J. A.;Brickman, A. M.;Reitz, C.;Cho, S. J.;Schupf, N.;Manly, J. J.;Tang, M. X.;Small, S. A.;Mayeux, R.;DeCarli, C.;Brown, T. R.",2009,Aug 11,10.1212/WNL.0b013e3181b1636a,0,
2799,Accelerated unilateral radiographic huntingtonian changes following neoadjuvant chemotherapy for a nongerminomatous germ cell tumor leading to identification of occult disease in the dorsal striatum,"Basal ganglia nongerminomatous germ cell tumors comprise 10% to 15% of germ cell tumor and have substantial morbidity at the time of local failure. In this submitted image we present a case where neoadjuvant chemotherapy unmasked a unilateral caudate head loss consistent with Huntingtonian changes. Careful review of the patient's imaging identified disease within the dorsal striatum that was not previously identified at the time of diagnosis. Review of the diffusion tensor fractional anisotropy imaging identified progressive white matter likely secondary to the occult disease within the dorsal striatum. Although this patient was asymptomatic and had no signs of a movement disorder, similar findings have been noted to be a prelude to such findings several months later. The occult disease was incorporated into the patient's radiotherapy planning target volume as oversight of these changes would have led to a marginal miss and potential early disease relapse.",,"Lucas, J. T.;Zapadka, M.;Houseknecht, K.;Buckley, K. S.;Couture, D. E.;Brown, D. R.",2016,2016,,0,
2800,[Cadasil: a new familial disease responsible for cerebral infarction and dementia] Cadasil: une nouvelle affection familiale responsable d'infarctus cerebraux et de demence,,Cerebral Arteries;Cerebral Infarction/ etiology/genetics;Dementia/ etiology/genetics;Female;Humans;Magnetic Resonance Imaging;Middle Aged;Recurrence,"Lucas, C.;Pasquier, F.;Leys, D.;Ruchoux, M. M.;Pruvo, J. P.",1995,,,0,
2801,[Cadasil: a new familial disease responsible for cerebral infarction and dementia],,*Cerebral Arteries;Cerebral Infarction/*etiology/genetics;Dementia/*etiology/genetics;Female;Humans;Magnetic Resonance Imaging;Middle Aged;Recurrence,"Lucas, C.;Pasquier, F.;Leys, D.;Ruchoux, M. M.;Pruvo, J. P.",1995,,,0,
2802,Dysthymic disorders and dementia of frontal lobe type,"The evolution of some dysthymic states towards dementia is now rarely considered whereas it was well known at the beginning of the century. In French the final stage of this evolution was known as 'demence vesanique'. In recent years it has been noted that a proportion of patients with presenile dementia do not have Alzheimer's disease (AD) but a particular type of cognitive impairment, called dementia of the frontal lobe type (DFT), characterised by clinical and neuropsychological signs of frontal lobe disorder as well as an anterior defect of cerebral perfusion or metabolism. The onset of DFT is insiduous and marked by personality changes and inappropriate affect. It has not yet been reported as starting with true dysthymic disorders. Patients and methods: Ten right handed patients (F/M = 9/1) became dysthymic in their fifties (m = 49.8 + 7.6 yr). All initially met the DSM III-R criteria for mood disorders. They were all treated with the standard drugs or ECT. Although initially responsive all the patients relapsed and their dysthymic disorders became less typical in presentation. At a mean age of 63.6 + 2.9 yrs a particular type of dementia became evident. None of the patients had a previous history of mood disorder or a family history of dementia. The demented patients received thorough clinical examinations and 8/10 were tested with the Wechsler Adult Intelligence Scale (WAIS). All had XCT and HMPAO-SPECT scans using a rotating gamma camera. Three patients had a MRI Scan. Results: The main symptoms were apathy and a lack of spontaneity as a result of which the patients were no longer able to live alone. HMPAO-SPECT: All the patients had clear hypoperfusion of the frontal and temporal lobes with seven showing a left predominance. XCT: A moderate degree of cortical atrophy, more pronounced in the frontal lobes, was observed in 6 patients. In 3 of them a previous XCT scan had been normal. MRI: Subcortical white matter hyperintensities were seen in the 3 patients examined. Discussion: Although our patients do not probably form, with regard to an etiology a homogeneous group, they share common characteristics which are very similar to those which differentiates DFT from AD. We postulate that some dysthymic disorders of the presenium might represent the initial stage of this type of dementia. This hypothesis relies on the evidence for frontal dysregulation in mood disorders as demonstrated, for example, by PET studies. In these cases the cortical abnormalities usually disappear as the dysthymia improves and are considered functional phenomena. They may correspond to the mechanism of deafferentation (or diaschisis). This implies a primary lesion, presumably located at a subcortical level (for instance a white matter lesion) producing a disruption of function in a distant (initially) intact brain region. As a supplementary hypothesis we propose that with time, and for as yet unknown reasons, the frontal hypoperfusion in our patients lost its reversibility and that, as a result, a particular type of dementia became manifest. In some cases this diaschisis protractiva may lead to secondary cortical atrophy. Conclusions: A DFT was found in 10 patients who had become dysthymic in their fifties. A pathogenic hypothesis i.e. diaschisis protractiva, is proposed, based on the evidence of neuroimaging studies.",adult;apathy;article;brain atrophy;brain blood flow;clinical article;dementia;dysthymia;female;frontal lobe;human;male;personality disorder,"Luaute, J. P.;Favel, P.;Reny, C.;Sanabria, E.;Bidault, E.",1994,,,0,
2803,Fatal familial insomnia with abnormal signals on routine MRI: A case report and literature review,"Background: Fatal familial insomnia (FFI) is a rare autosomal dominant disease caused by the PRNP D178N/129 M mutation. Routine brain CT and MRI usually reveal non-specific features. We report a patient with FFI presenting with diffuse abnormal signals on MRI, later confirmed as combined with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Case presentation: The patient was a 58-year-old female, whose main clinical manifestations were insomnia, movement disorders, autonomic hyperactivity and mental deterioration. The patient also suffered a typical episode of transient global amnesia. MRI indicated a diffuse white matter abnormality and microbleeding on the susceptibility-weighted imaging. On biopsy, the brain tissue sections showed spongiform changes with gliosis, neuronal degeneration, and prion protein deposition in a portion of the neurons. In addition, arteriosclerosis was prominent. Transmission electron microscopy showed osmiophilic particle deposition in the matrix of medial smooth muscle cells. Gene sequencing confirmed a diagnosis of FFI with CADASIL. Conclusions: This case is a compelling example that even with evidence of leukoencephalopathy, prion disease should be an important differential diagnosis of rapidly progressive dementia and related diseases. In cases of genetic diseases with atypical manifestations, the coexistence of two or even more diseases should be considered as a possible explanation.",fluorodeoxyglucose f 18;prion protein;adult;arteriosclerosis;article;autosomal dominant inheritance;basal ganglion;brain spongiosis;brain tissue;CADASIL;case report;clinical feature;Creutzfeldt Jakob disease;differential diagnosis;fatal familial insomnia;female;gene sequence;genetic disorder;gliosis;human;insomnia;limb movement;long term memory;magnetic resonance angiography;mental deterioration;middle aged;motor dysfunction;nerve cell degeneration;nuclear magnetic resonance imaging;positron emission tomography;prion disease;short term memory;sleep disorder;sleep time;smooth muscle cell;susceptibility weighted imaging;thalamus;transient global amnesia;transmission electron microscopy;white matter lesion;x-ray computed tomography,"Lu, T.;Pan, Y.;Peng, L.;Qin, F.;Sun, X.;Lu, Z.;Qiu, W.",2017,,10.1186/s12883-017-0886-2,0,
2804,Patterns of brain atrophy in clinical variants of frontotemporal lobar degeneration,"BACKGROUND/AIMS: The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups. METHODS: Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects. RESULTS: Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology. CONCLUSION: The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex.","Aged;Algorithms;Atrophy;Behavior/physiology;Brain/ pathology;Cognition/physiology;Diffusion Tensor Imaging;Disease Progression;Executive Function;Female;Frontotemporal Lobar Degeneration/ pathology;Humans;Image Processing, Computer-Assisted;Language;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychomotor Performance/physiology","Lu, P. H.;Mendez, M. F.;Lee, G. J.;Leow, A. D.;Lee, H. W.;Shapira, J.;Jimenez, E.;Boeve, B. B.;Caselli, R. J.;Graff-Radford, N. R.;Jack, C. R.;Kramer, J. H.;Miller, B. L.;Bartzokis, G.;Thompson, P. M.;Knopman, D. S.",2013,,000345523,0,
2805,Myelin breakdown mediates age-related slowing in cognitive processing speed in healthy elderly men,"BACKGROUND: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). MATERIALS AND METHODS: The prefrontal lobe white matter and the genu of the corpus callosum myelinate later in brain development (late-myelinating white matter; LMWM) and are more vulnerable to breakdown due to the effects of normal aging. An in vivo MRI biomarker of myelin integrity (transverse relaxation rates; R(2)) of LMWM was obtained for 38 very healthy elderly adult men (mean age=66.3 years; SD=6.0; range=55-76). To evaluate regional specificity, we also assessed a contrasting early-myelinating region (splenium of the corpus callosum; SWM), which primarily contains axons involved in visual processing. CPS was assessed using the Trail Making Test. RESULTS: LMWM R(2) and CPS measures were significantly correlated (r=.515, p=.0009), but no significant association between R(2) and CPS was detected in the splenium (p=.409). LMWM R(2), but not SWM R(2), was a significant mediator of the relationship between age and CPS (p=.037). CONCLUSIONS: In this very healthy elderly sample, age-related slowing in CPS is mediated by myelin breakdown in highly vulnerable late-myelinating regions but not in the splenium.","Age Factors;Aged;*Cognition;Humans;Magnetic Resonance Imaging/methods;Male;Mental Processes/*physiology;Middle Aged;Myelin Sheath/*metabolism/pathology;Nerve Fibers, Myelinated/*physiology;Neuropsychological Tests;Time Factors","Lu, P. H.;Lee, G. J.;Tishler, T. A.;Meghpara, M.;Thompson, P. M.;Bartzokis, G.",2013,Feb,10.1016/j.bandc.2012.09.006,0,
2806,Regional differences in white matter breakdown between frontotemporal dementia and early-onset Alzheimer's disease,"BACKGROUND: White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). OBJECTIVE: Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. METHODS: We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. RESULTS: Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. CONCLUSIONS: The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group.","Affective Symptoms/diagnosis/pathology;Aged;Alzheimer Disease/diagnosis/ pathology;Anisotropy;Brain/ pathology;Corpus Callosum/pathology;Diffusion Tensor Imaging;Female;Frontal Lobe/pathology;Frontotemporal Dementia/diagnosis/ pathology;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Psychiatric Status Rating Scales","Lu, P. H.;Lee, G. J.;Shapira, J.;Jimenez, E.;Mather, M. J.;Thompson, P. M.;Bartzokis, G.;Mendez, M. F.",2014,,10.3233/jad-131481,0,
2807,Age-related slowing in cognitive processing speed is associated with myelin integrity in a very healthy elderly sample,"Performance on measures of cognitive processing speed (CPS) slows with age, but the biological basis associated with this cognitive phenomenon remains incompletely understood. We assessed the hypothesis that the age-related slowing in CPS is associated with myelin breakdown in late-myelinating regions in a very healthy elderly population. An in vivo magnetic resonance imaging (MRI) biomarker of myelin integrity was obtained from the prefrontal lobe white matter and the genu of the corpus callosum for 152 healthy elderly adults. These regions myelinate later in brain development and are more vulnerable to breakdown due to the effects of normal aging. To evaluate regional specificity, we also assessed the splenium of the corpus callosum as a comparison region, which myelinates early in development and primarily contains axons involved in visual processing. The measure of myelin integrity was significantly correlated with CPS in highly vulnerable late-myelinating regions but not in the splenium. These results have implications for the neurobiology of the cognitive changes associated with brain aging. © 2011 Psychology Press.",,"Lu, P. H.;Lee, G. J.;Raven, E. P.;Tingus, K.;Khoo, T.;Thompson, P. M.;Bartzokis, G.",2011,2011,,0,
2808,MRI mapping of cerebrovascular reactivity via gas inhalation challenges,"The brain is a spatially heterogeneous and temporally dynamic organ, with different regions requiring different amount of blood supply at different time. Therefore, the ability of the blood vessels to dilate or constrict, known as Cerebral-Vascular-Reactivity (CVR), represents an important domain of vascular function. An imaging marker representing this dynamic property will provide new information of cerebral vessels under normal and diseased conditions such as stroke, dementia, atherosclerosis, small vessel diseases, brain tumor, traumatic brain injury, and multiple sclerosis. In order to perform this type of measurement in humans, it is necessary to deliver a vasoactive stimulus such as CO2 and/or O2 gas mixture while quantitative brain magnetic resonance images (MRI) are being collected. In this work, we presented a MR compatible gas-delivery system and the associated protocol that allow the delivery of special gas mixtures (e.g., O2, CO2, N2, and their combinations) while the subject is lying inside the MRI scanner. This system is relatively simple, economical, and easy to use, and the experimental protocol allows accurate mapping of CVR in both healthy volunteers and patients with neurological disorders. This approach has the potential to be used in broad clinical applications and in better understanding of brain vascular pathophysiology. In the video, we demonstrate how to set up the system inside an MRI suite and how to perform a complete experiment on a human participant.","Administration, Inhalation;Brain/ blood supply;Brain Mapping/ methods;Carbon Dioxide/administration & dosage;Cerebrovascular Circulation/drug effects/ physiology;Humans;Magnetic Resonance Imaging/ methods;Nitrogen/administration & dosage;Oxygen/administration & dosage;Vasoconstrictor Agents/administration & dosage;Vasodilator Agents/administration & dosage","Lu, H.;Liu, P.;Yezhuvath, U.;Cheng, Y.;Marshall, O.;Ge, Y.",2014,,10.3791/52306,0,
2809,"Comparison of [(18)F]Flutemetamol and [(11)C]Pittsburgh Compound-B in cognitively normal young, cognitively normal elderly, and Alzheimer's disease dementia individuals","BACKGROUND: Understanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [(18)F]Flutemetamol (FMT) and [(11)C]PiB (PiB) PET in the same people. METHODS: Structural MRI, FMT PET and PiB PET were each performed in 30 young cognitively normal (yCN), 31 elderly cognitively normal (eCN) and 21 Alzheimer's disease dementia (AD) participants. PiB and FMT images for each participant were compared quantitatively using voxel- and region-based analyses. Region of interest (ROI) analyses included comparisons of grey matter (GM) regions as well as white matter (WM) regions. Regional comparisons of each tracer between different groups and comparisons of the two modalities within the different groups were performed. To compare mean SUVr between modalities, and between diagnostic groups, we used paired t-tests and Student's t-test, respectively. We also compared the ability of the two tracers to discriminate between diagnostic groups using AUROC estimates. The effect of using different normalization regions on SUVr values was also evaluated. RESULTS: Both FMT and PiB showed greater uptake throughout GM structures in AD vs. eCN or yCN. In all dual-modality group comparisons (FMT vs. PiB in yCN, eCN, and AD), greater WM uptake was seen with FMT vs. PiB. In yCN and eCN greater diffuse GM uptake was seen with FMT vs. PiB. When comparing yCN to eCN within each tracer, greater WM uptake was seen in eCN vs yCN. CONCLUSIONS: Flutemetamol and PiB show similar topographical GM uptake in AD and CN participants and the tracers show comparable group discrimination. Greater WM accumulation with FMT suggests that quantitative differences vs. PiB will be apparent when using WM or GM as a reference region. Both imaging tracers demonstrate increased WM uptake in older people. These findings suggest that using different amyloid tracers or different methods of analyses in serial brain imaging in an individual may result in artifactual amyloid change measurements. Clinical use of several amyloid tracers in the same patient will have challenges that need to be carefully considered.",,"Lowe, V. J.;Lundt, E.;Knopman, D.;Senjem, M. L.;Gunter, J. L.;Schwarz, C. G.;Kemp, B. J.;Jack, C. R., Jr.;Petersen, R. C.",2017,,,0,
2810,Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL,"Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Walinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.","Adult;Brain/blood supply/ultrastructure;CADASIL/ genetics;Chromosome Mapping/methods;DNA Mutational Analysis/methods;Dementia, Multi-Infarct/ genetics/metabolism/pathology;Female;Humans;Intracranial Arteriosclerosis/genetics/pathology;Magnetic Resonance Imaging;Male;Microcirculation/metabolism;Middle Aged;Mutation;Pedigree;Polymerase Chain Reaction/methods;Receptors, Notch/ genetics/metabolism;Skin/ultrastructure","Low, W. C.;Junna, M.;Borjesson-Hanson, A.;Morris, C. M.;Moss, T. H.;Stevens, D. L.;St Clair, D.;Mizuno, T.;Zhang, W. W.;Mykkanen, K.;Wahlstrom, J.;Andersen, O.;Kalimo, H.;Viitanen, M.;Kalaria, R. N.",2007,Feb,10.1093/brain/awl360,0,
2811,The fornix and limbic system,"The limbic system is predominantly involved in memory and emotional output. Its 2 principle components are the hippocampus (involved in memory as part of the Papez circuit) and the amygdala (involved in emotional responses, memories and drives). The principle clinical manifestations of limbic disease are epilepsy, confusional states, and cognitive impairment. The connections of the limbic system are widespread and are now becoming visible on diffusion tensor imaging. Many different diseases may affect the limbic system. An appreciation of its functional anatomy along with its white matter tract connections improves assessment of infiltrative disease in particular. Small lesions in the Papez circuit may have devastating neuropsychological consequences. An active search strategy based on the knowledge presented in this paper will increase the likelihood of making an accurate diagnosis for patients affected by these conditions.",,"Lövblad, K. O.;Schaller, K.;Isabel Vargas, M.",2014,1,,0,
2812,Magnetic resonance imaging of vascular diseases of the white matter,"Magnetic resonance imaging plays an important role in the diagnosis and management of cerebrovascular diseases. In addition to stroke, it can also demonstrate changes apparent in the white matter such as leukoaraiosis. These as well as other changes occurring with increasing age can be visualized. Among others, there is an increase in the number and size of perivascular spaces. Although many of these alterations may be clinically silent, with increasing load they may become symptomatic. Other vascular pathological findings such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the posterior reversible encephalopathy syndrome can also provoke changes in the cerebral white matter that are visible on magnetic resonance imaging and are discussed. Copyright © 2010 by Lippincott Williams & Wilkins.",,"Lövblad, K. O.;Assal, F.;Pereira, V. M.;Vargas, M. I.;Sztajzel, R.;Haller, S.",2009,December,,0,
2813,Quantitative brain measurements in community-dwelling elderly persons with mild parkinsonian signs,"BACKGROUND: Mild parkinsonian signs (MPS) are a marker of incident dementia. They have been linked with cerebrovascular disease, which can be evaluated using magnetic resonance imaging (MRI). Also, if MPS are a marker for developing Alzheimer-type changes, hippocampal volume on MRI might be diminished in individuals with MPS. OBJECTIVE: To examine white matter hyperintensity (WMH) volume and total hippocampal volume in elderly individuals with and without MPS. METHODS: Community-dwelling elderly persons in northern Manhattan (New York), New York, underwent neurologic examination and brain MRI. The WMH volume (derived from fluid-attenuated inversion recovery-weighted MRIs using a semiautomated thresholding approach) and total hippocampal volume (derived manually) were expressed relative to total cranial volume. RESULTS: Mild parkinsonian signs were present in 111 of 666 participants (16.7%). Mean (SD) relative WMH volume was larger in participants with MPS vs those without MPS (1.70 [1.28] vs 1.17 [1.18]; P<.001). In a multivariate logistic regression analysis adjusting for age, sex, race/ethnicity, years of educational achievement, and depression, relative WMH volume was associated with MPS (odds ratio, 1.26; 95% confidence interval, 1.08-1.47; P=.004). In both unadjusted and adjusted analyses, total relative hippocampal volume was similar in participants with MPS vs those without MPS regardless of cognitive status. CONCLUSIONS: In this MRI study of community-dwelling elderly persons, WMH volume was associated with MPS and total relative hippocampal volume was not. These data raise the possibility that vascular disease could have a role in the development of MPS.","Aged;Aged, 80 and over;Brain Mapping;Female;Geriatric Assessment;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging/methods;Male;Neurologic Examination;Neuropsychological Tests;Parkinsonian Disorders/ pathology;Residence Characteristics","Louis, E. D.;Brickman, A. M.;DeCarli, C.;Small, S. A.;Marder, K.;Schupf, N.;Brown, T. R.",2008,Dec,10.1001/archneurol.2008.504,0,
2814,Diffusion-weighted magnetic resonance imaging in diagnosis of Creutzfeldt-Jakob disease,"BACKGROUND: Creutzfeldt-Jakob disease (CJD), a rare disease, is uncharacterized by computed tomography (CT) and magnetic resonance imaging (MRI). This study was aimed to evaluate the diffusion-weighted MRI (DWI) manifestations of CJD and to discuss their diagnostic value. METHODS: The findings of T(1)-weighted MRI (T(1)WI), T(2)-weighted MRI (T(2)WI), DWI and post-contrast MRI in 5 patients (3 patients with biopsy-proven CJD and 2 patients with clinically-proven CJD) were retrospectively analyzed in this study. RESULTS: Four out of the 5 patients had cerebral atrophy of various degrees. One patient showed symmetric high signal intensity at the bilateral globus pallidus and the head of the caudate nucleus, with very high signal in the cerebral cortex on the DWI. This patient only had symmetric slightly high signal at the bilateral globus pallidus and putamen on T(2)WI. One patient had high signal intensity at the basal ganglia and cerebral cortex on DWI, but abnormal T(2) signal intensity at the bilateral paraventricular white matter on MRI. Two patients presented with widely gyri-like high signal intensity at the cortex on DWI, but routine MRI showed bilateral paraventricular long T(2) signal intensity in 1 patient and no abnormal findings in another. No abnormalities were shown by both routine MRI and DWI in the last patient. CONCLUSIONS: DWI is more sensitive than its conventional counterpart in the depiction of CJD. DWI is more sensitive to detect cortical abnormal signal intensity in CJD not detected by T(2)WI.",Adult;Aged;Atrophy;Brain/ pathology;Creutzfeldt-Jakob Syndrome/diagnosis/ pathology/physiopathology;Diffusion Magnetic Resonance Imaging/ methods;Electroencephalography;Female;Humans;Male;Middle Aged,"Lou, X.;Ma, L.;An, N. Y.;Cai, Y. Q.;Liang, Y.;Guo, X. G.",2006,Aug 5,,0,
2815,Relationship between white-matter hyperintensities and hematoma volume and growth in patients with intracerebral hemorrhage,"BACKGROUND AND PURPOSE-: The presence of white-matter hyperintensities (WMHs) has been linked to intracerebral hemorrhage (ICH). We sought to determine whether the severity of WMHs influences hematoma growth and ICH volume. METHODS-: We retrospectively reviewed prospectively collected clinical, laboratory, and radiologic data from 79 consecutive ICH patients who had brain magnetic resonance imaging performed within 72 hours of ICH symptom onset. We assessed the severity of WMHs on magnetic resonance imaging on the modified Scheltens scale and performed logistic-regression analysis to examine the association between WMHs and ICH volume. We also examined the association between WMH score and hematoma growth in a subset of 34 patients who had a baseline computed tomography scan within 12 hours of ICH onset and a follow-up scan within 72 hours. RESULTS-: The ICH volume at 37.6±22.3 hours from ICH onset was 2-fold higher in patients with a high WMH score (≥14) than in those with a lower score. A high WMH score was independently associated with a larger ICH volume (odds ratio=1.152; 95% CI, 1.035 to 1.282; P=0.01). There was a trend for an association between WMH score and ICH volume growth (odds ratio=1.286; 95% CI, 0.978 to 1.692; P=0.062). CONCLUSION-: Severe WMHs are associated with larger ICH volumes and, to a lesser extent, with hematoma growth. Our findings suggest that WMHs may provide important prognostic information on patients with ICH and may have implications for treatment stratification. These findings require prospective validation, and the links between WMHs and ICH growth require further investigations. © 2009 American Heart Association, Inc.",,"Lou, M.;Al-Hazzani, A.;Goddeau, R. P.;Novak, V.;Selim, M.",2010,January,,0,
2816,Subcortical arteriosclerotic encephalopathy: CT spectrum and pathologic correlation,"Because of recent papers suggesting that subcortical arteriosclerotic encephalopathy (SAE) (Binswanger's disease) is more common than historically assumed, this investigation was initiated to assess the frequency of SAE, to gauge the reliability of CT in making this diagnosis, and to assess the strength of the correlation between SAE and arterial hypertension. Of 202 autopsied patients in a 17-month period, 82 had undergone antemortem CT. Of these, 20 had CT findings thought to represent varying degrees of the disease spectrum of SAE. Microscopy confirmed this diagnosis in 18 cases. The pattern of diminished attenuation in the white matter was periventricular in 16 patients (marked asymmetry in one) and limited to an isolated focus somewhat removed from the ependyma in two. Among the 16 with periventricular disease, the extent of the process by CT appeared mild in nine, moderate in five, and severe only in two. There were two false positive CT diagnoses of SAE. Among a control group of 10 patients with normal white matter by CT, seven had microscopic evidence of SAE, although it was generally less severe than in those with positive CT scans. Subcortical arteriosclerotic encephalopathy is common and can be identified in its various forms by CT with a high degree of reliability.",autopsy;brain atherosclerosis;brain disease;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;etiology;histology;human;human cell;major clinical study;peripheral vascular system,"Lotz, P. R.;Ballinger Jr, W. E.;Quisling, R. G.",1986,,,0,
2817,White matter fiber tracking directed by interpolating splines and a methodological framework for evaluation,"Image-based tractography of white matter (WM) fiber bundles in the brain using diffusion weighted MRI (DW-MRI) has become a useful tool in basic and clinical neuroscience. However, proper tracking is challenging due to the anatomical complexity of fiber pathways, the coarse resolution of clinically applicable whole-brain in vivo imaging techniques, and the difficulties associated with verification. In this study we introduce a new tractography algorithm using splines (denoted Spline). Spline recon structs smooth fiber trajectories iteratively, in contrast to most other tractography algorithms that create piecewise linear fiber tract segments, followed by spline fitting. Using DW-MRI recordings from eight healthy elderly people participating in a longitudinal study of cognitive aging, we compare our Spline algorithm to two state-of-the-art tracking methods from the TrackVis software suite. The comparison is done quantitatively using diffusion metrics (fractional anisotropy, FA), with both (i) tract averaging, (ii) longitudinal linear mixed-effects model fitting, and (iii) detailed along-tract analysis. Further validation is done on recordings from a diffusion hardware phantom, mimicking a coronal brain slice, with a known ground truth. Results from the longitudinal aging study showed high sensitivity of Spline tracking to individual aging patterns of mean FA when combined with linear mixed-effects modelling, moderately strong differences in the along-tract analysis of specific tracts, whereas the tract-averaged comparison using simple linear OLS regression revealed less differences between Spline and the two other trac tography algorithms. In the brain phantom experiments with a ground truth, we demonstrated improved tracking ability of Spline compared to the two reference tractography algorithms being tested. © 2013 Losnegård, Lundervold and Hodneland.",,"Losnegård, A.;Lundervold, A.;Hodnelanda, E.",2013,,,0,
2818,Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum,"We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E epsilon4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E epsilon4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ epidemiology/psychology;Cognition Disorders/ diagnosis/ epidemiology/psychology;Cross-Sectional Studies;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Middle Aged;Risk Factors;Vascular Diseases/ diagnosis/ epidemiology/psychology","Lorius, N.;Locascio, J. J.;Rentz, D. M.;Johnson, K. A.;Sperling, R. A.;Viswanathan, A.;Marshall, G. A.",2015,Jan-Mar,10.1097/wad.0000000000000043,0,
2819,Biochemical changes in the frontal lobe of HIV-infected individuals detected by magnetic resonance spectroscopy,"We have developed a proton magnetic resonance spectroscopy method that selectively can sample cortical gray matter and adjacent white matter in the frontal lobe. We have used this approach to study a group of patients (n = 7) infected with HIV and clinical manifestations of the AIDS dementia complex (ADC), a group of patients (n = 8) infected with HIV without any indications of ADC, and seven controls. The patients without ADC had a statistically significant increase in the ratio of myo-inositol to creatine in white matter compared with normal controls. In contrast, the group of patients with ADC had almost normal levels of myo-inositol to creatine in both gray matter and white matter and showed a statistically significant decrease in the N-acetylaspartate to creatine ratio in gray matter compared with either the normal controls or the patients without ADC. Patterns of spectral abnormalities correlated with neuropsychological measures of frontal lobe dysfunction, suggesting that the evaluation of frontal lobe metabolism by magnetic resonance spectroscopy can play a role in the early detection of ADC, in determining its progression, and in assessing responses to therapeutic interventions.",*AIDS Dementia Complex/metabolism;Adult;*Brain Chemistry;Creatine;Female;Frontal Lobe/*chemistry/metabolism/radiography;*HIV Infections/complications/metabolism;*Hiv-1;Humans;Inositol;Magnetic Resonance Imaging;Male;Middle Aged,"Lopez-Villegas, D.;Lenkinski, R. E.;Frank, I.",1997,Sep 2,,0,
2820,"Diffusion Tensor Imaging, Intracranial Vascular Resistance and Cognition in Middle-Aged Asymptomatic Subjects","Background: The contribution of traditional vascular risk factors to cognitive impairment and dementia is well known. However, in order to obtain possible targets for prevention of vascular cognitive impairment (VCI), it may be important to identify other early and noninvasive markers in asymptomatic middle-aged adults. The calculation of middle cerebral artery-pulsatility index (MCA-PI) is an ultrasonologic, noninvasive, validated and easily reproducible technique to assess increased distal resistance to blood flow. This study aims to assess the relationship between MCA-PI, microstructural white matter (WM) integrity and cognition in a middle-aged asymptomatic population. Methods: Ninety-five participants from the Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) neuropsychology study were included. Subjects were 50-65 years old, free from dementia and without history of vascular disease. Transcranial color-coded duplex ultrasound examination was performed to assess MCA-PI as a measure of vascular resistance. WM integrity was evaluated by fractional anisotropy (FA) measurements of diffusion tensor images (DTI) acquired on a 3T-MRI. The neuropsychological battery was specifically selected to be sensitive to VCI, and included tests that were grouped into six cognitive domains: executive functioning, attention, verbal fluency, memory, visuospatial skills and psychomotor speed. A multivariate linear regression model adjusted for age, gender, years of education, diabetes and hypertension was performed. Results: MCA-PI was significantly associated with WM disintegration in different tracts (fornix, corticospinal and anterior thalamic), all p < 0.05 uncorrected. Both mean MCA-PI and mean FA of those significant tracts were independently associated with poor performance in attention, psychomotor speed, and visuospatial skills after adjustment for age, gender, years of education, and vascular risk factors (all p < 0.05). MCA-PI was independently associated with lower scores in all cognitive domains, except for visuospatial skills. Conclusions: Our data suggest that MCA-PI may be related to WM disintegration and early vascular cognitive impairment in middle-aged subjects. Although further prospective studies are needed to provide evidence for its validity in longitudinal studies, our results support the proposal of including MCA-PI as part of clinical assessment in order to identify targets for VCI prevention. © 2014 S. Karger AG, Basel.",,"López-Olóriz, J.;López-Cancio, E.;Arenillas, J. F.;Hernández, M.;Dorado, L.;Dacosta-Aguayo, R.;Barrios, M.;Soriano-Raya, J. J.;Miralbell, J.;Bargalló, N.;Cáceres, C.;Torán, P.;Alzamora, M.;Dávalos, A.;Mataró, M.",2014,2,,0,
2821,Endovascular treatment improves cognition after stroke,"Objective: To investigate the effect of endovascular treatment on cognitive function as a prespecified secondary analysis of the REVASCAT (Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours) trial. Methods: REVASCAT randomized 206 patients with anterior circulation proximal arterial occlusion stroke to Solitaire thrombectomy or best medical treatment alone. Patients with established dementia were excluded from enrollment. Cognitive function was assessed in person with Trail Making Test (TMT) Parts A and B at 3 months and 1 year after randomization by an investigator masked to treatment allocation. Test completion within 5 minutes, time of completion (seconds), and number of errors were recorded. Results: From November 2012 to December 2014, 206 patients were enrolled in REVASCAT. TMT was assessed in 82 of 84 patients undergoing thrombectomy and 86 of 87 control patients alive at 3 months and in 71 of 79 patients undergoing thrombectomy and 72 of 78 control patients alive at 1 year. Rates of timely TMT-A completion were similar in both treatment arms, although patients undergoing thrombectomy required less time for TMT-A completion and had higher rates of error-free TMT-A performance. Thrombectomy was also associated with a higher probability of timely TMT-B completion (adjusted odds ratio 3.17, 95% confidence interval 1.51-6.66 at 3 months; and adjusted ratio 3.66, 95% confidence interval 1.60-8.35 at 1 year) and shorter time for TMT-B completion. Differences in TMT completion times between treatment arms were significant in patients with good functional outcome but not in those who were functionally dependent (modified Rankin Scale score >2). Poorer cognitive outcomes were significantly associated with larger infarct volume, higher modified Rankin Scale scores, and worse quality of life. Conclusions: Thrombectomy improves TMT performance after stroke, especially among patients who reach good functional recovery. ClinicalTrials.gov identifier: NCT01692379. Classification of evidence: This study provides Class I evidence that for patients with stroke from acute anterior circulation proximal arterial occlusion, thrombectomy improves performance on the TMT at 3 months. Copyright 2016 American Academy of Neurology.",article;brain infarction size;brain ischemia;cerebrovascular accident su [Surgery];cognition;controlled study;endovascular surgery;EuroQoL Group 5-Dimension Self-Report Questionnaire;executive function;female;human;language disability;major clinical study;male;National Institutes of Health Stroke Scale;neuropsychological test;nuclear magnetic resonance imaging;paresis;pharmaceutical care;priority journal;quality of life;questionnaire;randomized controlled trial;Rankin scale;secondary analysis;thrombectomy;trail making test;treatment outcome;visual analog scale;working memory;X ray computed tomography;artery occlusion;cerebrovascular accident;classification;confidence interval;controlled clinical trial;dementia;error;infarction;normal human;odds ratio;probability;randomization;remission,"Lopez-Cancio, E.;Jovin, T. G.;Cobo, E.;Cerda, N.;Jimenez, M.;Gomis, M.;Hernandez-Perez, M.;Caceres, C.;Cardona, P.;Lara, B.;Renu, A.;Llull, L.;Boned, S.;Muchada, M.;Davalos, A.",2017,,,0,
2822,Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study,"OBJECTIVES: To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study. METHODS: We determined the plasma A beta 1-40 and A beta 1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 +/- 3.6 years. We examined the association between A beta levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts. RESULTS: In an unadjusted prospective model in normal subjects, both A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD. CONCLUSIONS: Plasma A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of A beta do not seem to be useful biomarkers for AD.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/*blood/*epidemiology/physiopathology;Amyloid beta-Peptides/*blood;Apolipoprotein E4/genetics;Biomarkers/analysis/blood;Brain/*metabolism/pathology/physiopathology;Cerebrovascular Disorders/epidemiology;Comorbidity;Cross-Sectional Studies;Cystatin C;Cystatins/blood;Female;Humans;Incidence;Longitudinal Studies;Magnetic Resonance Imaging;Male;Models, Statistical;Neuropsychological Tests;Peptide Fragments/*blood;Predictive Value of Tests;Prospective Studies;Reference Values;Risk Factors","Lopez, O. L.;Kuller, L. H.;Mehta, P. D.;Becker, J. T.;Gach, H. M.;Sweet, R. A.;Chang, Y. F.;Tracy, R.;DeKosky, S. T.",2008,May 6,10.1212/01.wnl.0000306696.82017.66,0,
2823,Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2,"OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.",Aged;Apolipoprotein E4;Apolipoproteins E/genetics;Brain/pathology;Cardiovascular Diseases/ epidemiology/genetics/ psychology;Cognition Disorders/ epidemiology/genetics/ psychology;Cohort Studies;Depressive Disorder/complications/psychology;Female;Humans;Logistic Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mood Disorders/epidemiology;Pennsylvania/epidemiology;Population;Risk Factors,"Lopez, O. L.;Jagust, W. J.;Dulberg, C.;Becker, J. T.;DeKosky, S. T.;Fitzpatrick, A.;Breitner, J.;Lyketsos, C.;Jones, B.;Kawas, C.;Carlson, M.;Kuller, L. H.",2003,Oct,10.1001/archneur.60.10.1394,0,
2824,Electroencephalographic correlates of periventricular white matter lesions in probable Alzheimer's disease,"We evaluated the relationship between periventricular white matter lesions (PWMLs) and EEG abnormalities in probable Alzheimer's disease (AD). We visually analyzed the EEG of 27 probable AD patients with mild to moderate degree of cognitive impairment participating in a longitudinal study of dementia. Patients had both CT and MRI scans performed at baseline examination, which also included an EEG. PWMLs were rated in CT and MRI films using a semiquantitative method. The EEGs were classified according to the Mayo Clinic Classification System. Abnormal EEGs correlated with PWMLs rating scores were detected on CT, but not on MRI. These data suggest that the presence of PWMLs contribute to the abnormal EEGs observed in AD patients, and that white matter abnormalities in CT correlate better with both the clinical findings and EEG than does the more sensitive but less specific MRI.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/*physiopathology/radiography;Cerebral Ventricles/*pathology;Cerebral Ventriculography;*Electroencephalography;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Lopez, O. L.;Brenner, R. P.;Becker, J. T.;Jungreis, C. A.;Rezek, D.;DeKosky, S. T.",1995,Nov-Dec,,0,
2825,Psychiatric correlates of MR deep white matter lesions in probable Alzheimer's disease,"The authors examined the relationship between psychiatric symptoms and the presence of of MR deep white matter lesions (DWMLs) in 28 probable Alzheimer's disease (AD) patients with mild to moderate dementia. The difference in frequency of psychiatric symptoms between patients with and without DWMLs was not statistically significant. However, MR global scores of severity correlated with the presence of ideational disturbances (such as low self-esteem and suicidal ideation). Analysis of specific cerebral regions indicated that the highest correlation occurred in the frontal white matter. Thus, DWMLs are correlated with specific symptoms of depression in AD. Whether DWMLs are etiologically related to these symptoms remains to be determined.",Aged;Alzheimer Disease/*pathology/psychology;Brain/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Mental Disorders/diagnosis/psychology;Middle Aged;Psychiatric Status Rating Scales,"Lopez, O. L.;Becker, J. T.;Reynolds, C. F., 3rd;Jungreis, C. A.;Weinman, S.;DeKosky, S. T.",1997,Spring,10.1176/jnp.9.2.246,0,
2826,Computed tomography--but not magnetic resonance imaging--identified periventricular white-matter lesions predict symptomatic cerebrovascular disease in probable Alzheimer's disease,"OBJECTIVE: To examine the clinical consequences of periventricular white-matter lesions on computed tomography (CT) and magnetic resonance imaging (MRI) scans in probable Alzheimer's disease. DESIGN: Case series, 12-month follow-up. SETTING: Multidisciplinary behavioral neurology research clinic. PATIENTS: We longitudinally evaluated the clinical characteristics of 27 patients with probable AD for whom both CT and MRI scans had been performed at baseline. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The presence of abnormal neurological signs was examined at baseline and at a 12-month examination. RESULTS: Periventricular white-matter lesions were observed with CT in 12 patients (44%) and with MRI in 21 patients (78%). Computed tomography did not detect lesions of 1 to 3 mm, as were seen on MRI scans, and CT also did not detect lesions of 4 to 10 mm when they occurred in the deep subcortical white matter and were not part of a greater confluent lesion. There was no relationship between the severity of periventricular white-matter lesions with either neuroimaging method and the presence of abnormal neurological signs. However, there was a greater frequency of periventricular white-matter lesions shown on CT scans than on MRI scans at baseline in patients in whom abnormal neurological signs (eg, abnormal gait, asymmetric deep tendon reflexes, focal motor deficits, abnormal plantar response) developed at 12-month follow-up. CONCLUSION: Although MRI may be more sensitive in detecting periventricular white-matter lesions, CT is more specific in predicting subsequent symptomatic cerebrovascular disease.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/ radiography;Cerebral Ventricles/pathology;Cerebral Ventriculography;Cerebrovascular Disorders/pathology/ radiography;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Lopez, O. L.;Becker, J. T.;Jungreis, C. A.;Rezek, D.;Estol, C.;Boller, F.;DeKosky, S. T.",1995,Jul,,0,
2827,Genes from a translational analysis support a multifactorial nature of white matter hyperintensities,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS: We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. RESULTS: Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7x10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS: Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.","Aged;Alzheimer Disease/diagnosis/epidemiology/genetics;Animals;Brain/pathology;Causality;Dementia/diagnosis/epidemiology/genetics;Female;Genome-Wide Association Study/ methods;Humans;Leukoencephalopathies/ diagnosis/epidemiology/ genetics;Male;Polymorphism, Single Nucleotide/ genetics;Rats;Rats, Inbred SHR;Rats, Wistar;Risk Factors;Translational Medical Research/ methods;White Matter/ pathology","Lopez, L. M.;Hill, W. D.;Harris, S. E.;Valdes Hernandez, M.;Munoz Maniega, S.;Bastin, M. E.;Bailey, E.;Smith, C.;McBride, M.;McClure, J.;Graham, D.;Dominiczak, A.;Yang, Q.;Fornage, M.;Ikram, M. A.;Debette, S.;Launer, L.;Bis, J. C.;Schmidt, R.;Seshadri, S.;Porteous, D. J.;Starr, J.;Deary, I. J.;Wardlaw, J. M.",2015,Feb,10.1161/strokeaha.114.007649,0,
2828,[The evaluation of cognitive deterioration in transient ischemic attacks] Valoracion del deterioro cognitivo en el accidente isquemico transitorio (AIT),"We compared the degree of dementia in a group of 41 patients who, four years previously, had presented a first TIA with that of 31 healthy controls of similar age. For pathogenic diagnosis the Hachinski and Gustafson-Nilsson scales were applied, while mental state was evaluated by the Folstein, Blessed, GDS and CDR tests. We performed in all cases cerebral CT and several MR. The findings associated with dementia were the presence of multi-infarctions, leucoaraiosis or lacunes in the cerebral CT and the presentation of new ischemic episodes, sphincterian or gait disturbances and focal deficits. There were no differences with the control group in the cases only presenting one TIA. Polyglobulia was the only factor significantly associated with vascular dementia in these patients.","Age Factors;Aged;Brain/ physiopathology;Brain Diseases/complications/ physiopathology;Cognition Disorders/etiology/ physiopathology;Culture;Dementia, Multi-Infarct/etiology/physiopathology;Educational Status;Female;Humans;Hypertension;Ischemic Attack, Transient/complications/ physiopathology;Male;Middle Aged;Prevalence;Risk Factors","Lopez Gaston, J. I.;Martin, J.;Bertol, V.;Errea, J. M.;Pina, M. A.",1993,Jun-Jul,,0,
2829,[The evaluation of cognitive deterioration in transient ischemic attacks],"We compared the degree of dementia in a group of 41 patients who, four years previously, had presented a first TIA with that of 31 healthy controls of similar age. For pathogenic diagnosis the Hachinski and Gustafson-Nilsson scales were applied, while mental state was evaluated by the Folstein, Blessed, GDS and CDR tests. We performed in all cases cerebral CT and several MR. The findings associated with dementia were the presence of multi-infarctions, leucoaraiosis or lacunes in the cerebral CT and the presentation of new ischemic episodes, sphincterian or gait disturbances and focal deficits. There were no differences with the control group in the cases only presenting one TIA. Polyglobulia was the only factor significantly associated with vascular dementia in these patients.","Age Factors;Aged;Brain/*physiopathology;Brain Diseases/complications/*physiopathology;Cognition Disorders/etiology/*physiopathology;Culture;Dementia, Multi-Infarct/etiology/physiopathology;Educational Status;Female;Humans;Hypertension;Ischemic Attack, Transient/complications/*physiopathology;Male;Middle Aged;Prevalence;Risk Factors","Lopez Gaston, J. I.;Martin, J.;Bertol, V.;Errea, J. M.;Pina, M. A.",1993,Jun-Jul,,0,
2830,Post-stroke dementia: the contribution of thalamus and basal ganglia changes,"BACKGROUND: The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). METHODS: T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. RESULTS: The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; rho = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. CONCLUSION: Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Basal Ganglia/ pathology;Caudate Nucleus/pathology;Dementia/ etiology/pathology;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Neuroimaging;Putamen/pathology;Stroke/ complications/pathology;Thalamus/ pathology","Lopes, M. A.;Firbank, M. J.;Widdrington, M.;Blamire, A. M.;Kalaria, R. N.;O'Brien, J. T.",2012,Apr,10.1017/s1041610211002195,0,
2831,[Image characterization of Alzheimer's disease associated with the E280A-PS1 mutation. Case-control study: MRI findings] Caracterizacion imagenologica de la enfermedad de Alzheimer asociada a la mutacion E280A-PS1. Estudio caso-control: hallazgos en la resonancia magnetica,"INTRODUCTION AND METHODS: In order to compare the magnetic resonance image characteristics of individuals belonging to pedigrees carrying the mutation E280A-PS1 associated to early onset Alzheimer disease, coming from Antioquia, Colombia, 78 individuals were studied. 47 of them were carriers of the mutation, 23 of those presented symptoms and 31 individuals being controls (non carriers of the mutation). RESULTS: In summary, significative differences were appreciated between symptomatic individuals and those asymptomatic. There was not significant difference between asymptomatic carriers and the controls. The presence of the perihippocampal fissure constituted a difference statistically significant between the symptomatic individuals and those carriers asymptomatic and between the symptomatic ones and the controls. The interuncal distance increased significantly was another difference between symptomatic and asymptomatic individuals and among symptomatic and control group. The lobar atrophy and the ventriculomegaly were found in symptomatic individuals and they correlate with the disorder graveness. There was not significance in the presence of infarcts and/or hippocampal hyperintensities. CONCLUSION: These results corroborate the statement that magnetic resonance image is very useful in the diagnosis and follow-up of individuals affected by early onset Alzheimer disease.","0 (Membrane Proteins);0 (Nerve Tissue Proteins);0 (PSEN1 protein, human);0 (Presenilin-1);Age of Onset;Alzheimer Disease/diagnosis/epidemiology/genetics/ pathology;Atrophy;Case-Control Studies;Cerebral Ventricles/pathology;Colombia/epidemiology;Dementia/diagnosis;Diagnosis, Differential;Female;Genes, Dominant;Genetic Predisposition to Disease;Heterozygote;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Membrane Proteins/ genetics;Middle Aged;Nerve Tissue Proteins/ genetics;Point Mutation;Presenilin-1;Severity of Illness Index","Lopera, F.;Tobon, N.;Arcos-Burgos, M.;Vargas, S.;Gutierrez, J. E.;Rosselli, M.;Ardila, A.",1999,Jul 1-15,,0,
2832,Image characterization of Alzheimer's disease associated with the E280A-PS1 mutation. Case-control study: MRI findings,"INTRODUCTION AND METHODS: In order to compare the magnetic resonance image characteristics of individuals belonging to pedigrees carrying the mutation E280A-PS1 associated to early onset Alzheimer disease, coming from Antioquia, Colombia, 78 individuals were studied. 47 of them were carriers of the mutation, 23 of those presented symptoms and 31 individuals being controls (non carriers of the mutation). RESULTS: In summary, significative differences were appreciated between symptomatic individuals and those asymptomatic. There was not significant difference between asymptomatic carriers and the controls. The presence of the perihippocampal fissure constituted a difference statistically significant between the symptomatic individuals and those carriers asymptomatic and between the symptomatic ones and the controls. The interuncal distance increased significantly was another difference between symptomatic and asymptomatic individuals and among symptomatic and control group. The lobar atrophy and the ventriculomegaly were found in symptomatic individuals and they correlate with the disorder graveness. There was not significance in the presence of infarcts and/or hippocampal hyperintensities. CONCLUSION: These results corroborate the statement that magnetic resonance image is very useful in the diagnosis and follow-up of individuals affected by early onset Alzheimer disease.","Age of Onset;Alzheimer Disease/diagnosis/epidemiology/genetics/ pathology;Atrophy;Case-Control Studies;Cerebral Ventricles/pathology;Colombia/epidemiology;Dementia/diagnosis;Diagnosis, Differential;Female;Genes, Dominant;Genetic Predisposition to Disease;Heterozygote;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Membrane Proteins/ genetics;Middle Aged;Nerve Tissue Proteins/ genetics;Point Mutation;Presenilin-1;Severity of Illness Index","Lopera, F.;Tobon, N.;Arcos-Burgos, M.;Vargas, S.;Gutierrez, J. E.;Rosselli, M.;Ardila, A.",1999,Jul 1-15,,0,
2833,Segregation analysis of hereditary cerebrovascular disease in a large family from Antioquia (Colombia),"Introduction. Among different kinds of cerebrovascular diseases, few of them are caused by genetic disturbances, such as CADASIL (caused by Notch3 mutations), CARASIL, mitochondrial encephalopathy, MELAS and dementia typed Binswanger. However, to describe these type of cerebrovascular diseases related with genetic mutations could permit to determinate the causes of both hereditary and sporadic cerebrovascular diseases and then lead solutions. Objective. To describe the genetic, environmental and cohort factors that determinate the presence of many affected people by a several cerebrovascular diseases in the pedigree of a large family from Antioquia (Colombia). Patients and methods. We performed one pedigree (268 individuals), through singular recruit and then complex segregation analysis with POINTER program. Results. The model that more close to data is autosomal dominant mayor locus without influence of environmental factors. Frequency of allele of susceptibility to develop stroke or subcortical vascular dementia was 0.0006. Mayor gene is over epistatic effects or interactions with other gene. Conclusions. Described an autosomal dominant hereditary model through complex segregation analysis in a pedigree of patients with hereditary cerebral vascular diseases characterized by recurrent strokes, early onset subcortical dementia, hearing loss, antecedent of migraine and MRI signal abnormalities, subcortical infarcts and leukoencephalopathy. In this family the parameter calculated, autosomal dominant model, and clinical feature strongly support the diagnostic of CADASIL, linkage analysis and sequentiation will be performed to determinate if mutant gene is Notch3.",adolescent;adult;article;autosomal dominant disorder;brain infarction;cerebrovascular disease;child;clinical article;clinical feature;cohort analysis;Colombia;environmental factor;female;gene locus;genetic disorder;genetic linkage;genetic susceptibility;hearing impairment;heredity;human;infant;leukoencephalopathy;male;migraine;multiinfarct dementia;nuclear magnetic resonance imaging;pedigree;segregation analysis;cerebrovascular accident,"Lopera, F.;Rivera, N.;Arboleda, J.;Restrepo, T.;Arcos-Burgos, M.",2001,,,0,
2834,Clinical characteristics of hereditary cerebrovascular disease in a large family from Colombia,"INTRODUCTION: The cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene in the chromosome 19p13.1. and is characterized by small-vessel disease of the cerebral. The clinical feature consists of migraine, recurrent strokes, mood changes and dementia. OBJECTIVE: To describe the clinical phenotype of a Colombian family with hereditary cerebrovascular disease. PATIENTS AND METHODS: We performed one pedigree with 268 individuals, neurologic examination to 57 members and magnetic resonance imaging (MRI) to 25 of them. RESULTS: Clinical analysis strongly support the diagnosis of CADASIL because 12 individuals had suffered recurrent stroke, five of them later developed subcortical dementia. Two patients developed dementia without preceding stroke. All affected individuals by stroke or dementia whom were tested with MRI had white matter hyperintensities and subcortical infarcts (nine cases). Others seven individuals have MRI signal abnormalities like CADASIL, four of them are asymptomatic, one had suffered ischemic transient attacks and two had suffered migraine. Other 22 individuals had only migraine. We outstand the high frequency of MRI signal abnormalities in corpus callosum that we found in five individuals with stroke or dementia, the patient with ischemic transient attack and one asymptomatic patient, either the presence of hearing loss in seven individuals with stroke or dementia. CONCLUSIONS: We describe one large family with hereditary cerebrovascular disease characterized by recurrent strokes, subcortical dementia, hearing loss, migraine, and MRI signal abnormalities typed leukoencephalopathy, subcortical infarcts and alterations in corpus callosum. Clinical analysis strongly support the diagnosis of CADASIL.",,"Lopera, F.;Arboleda, J.;Moreno, S.;Almeida, N.;Cuartas, M.;Arcos-Burgos, M.",2000,2000,,0,
2835,Caudate nucleus volumes in stroke and vascular dementia,"We aimed to assess the volume of the nucleus caudatus as a neuroanatomical substrate of fronto-subcortical circuits, in stroke patients with/without dementia, and the relationship to potential determinants of neural circuit integrity such as white matter hyperintensities (WMH) and stroke volume. Stroke only (Stroke) (n=19) and stroke with Vascular Dementia (VaD) (n=16) and healthy control (n=20) subjects, matched on demographic variables, underwent extensive neuropsychiatric assessments and manual MRI-based volumetric measurements for intracranial area (ICA), stroke volume, and bilateral caudate volume. WMH on MRI were quantified using an automated algorithm. Multivariate analysis of covariance (controlling for age and ICA), revealed that across the three groups, caudate volumes were significantly different. There was a significant difference in bilateral caudate nucleus volume between subjects by diagnosis (Stroke, VaD, control). The control group was largest in overall mean volume of the diagnostic groups, followed by the Stroke group (86% of controls), and finally, the VaD group (72%). There was a partial correlation between total caudate volume and the total volume of deep WMH including periventricular regions and brainstem, controlling for ICA; and for total stroke volume. Stroke patients with VaD have smaller caudate nuclei compared to those without dementia and healthy controls, with the stroke-only patients being intermediate in their caudate volume status. There was preliminary evidence of negative correlation of caudate volume with volume of deep WMH and total stroke volume, suggesting cerebrovascular disease contributes to caudate atrophy,which, in turn may disrupt fronto-subcortical circuits.","Aged;Aged, 80 and over;*Brain Mapping;Caudate Nucleus/*pathology;Dementia, Vascular/*pathology;Female;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Multivariate Analysis;Retrospective Studies;Stroke/*pathology","Looi, J. C.;Tatham, V.;Kumar, R.;Maller, J. J.;Millard, E.;Wen, W.;Chen, X.;Brodaty, H.;Sachdev, P.",2009,Oct 30,10.1016/j.pscychresns.2009.04.002,0,
2836,Distinct laterality alterations distinguish mild cognitive impairment and Alzheimer's disease from healthy aging: Statistical parametric mapping with high resolution MRI,"Laterality of human brain varies under healthy aging and diseased conditions. The alterations in hemispheric asymmetry may embed distinct biomarkers linked to the disease dynamics. Statistical parametric mapping based on high-resolution magnetic resonance imaging (MRI) and image processing techniques have allowed automated characterization of morphological features across the entire brain. In this study, 149 subjects grouped in healthy young, healthy elderly, mild cognitive impairment (MCI), and Alzheimer's disease (AD) were investigated using multivariate analysis for regional cerebral laterality indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume measured on high-resolution MR images. Asymmetry alteration of MCI and AD were characterized by marked region-specific reduction, while healthy elderly featured a distinct laterality shift in the limbic system in addition to regional asymmetry loss. Lack of the laterality shift in limbic system and early loss of asymmetry in entorhinal cortex may be biomarkers to identify preclinical AD among other dementia. Multivariate analysis of hemispheric asymmetry may provide information helpful for monitoring the disease progress and improving the management of MCI and AD. © 2012 Wiley Periodicals, Inc.",,"Long, X.;Zhang, L.;Liao, W.;Jiang, C.;Qiu, B.",2013,December,,0,
2837,Cranial computed tomography in the diagnosis of multiple sclerosis,"A group of 202 patients with suspected, probable or definite multiple sclerosis was studied, using cranial computed tomography (CT). Atrophy alone, or in combination with white-matter and periventricular lucencies, and areas of contrast enhancement, were the main abnormal findings in 52% of patients. Atrophy was detected in 44% of patients, and its frequency and severity correlated with disease duration up to 10 years, age, and disease category. Atrophic changes in the brainstem and cerebellum could be correlated with clinical data more often than supratentorial atrophy could be correlated with features such as dementia or mood changes. Lucencies in the white matter, thought to represent areas of demyelination, were noted in 21% of patients, and only a proportion of these lesions could be correlated with clinical data, the others being clinically silent. Contrast enhancement was seen in a small proportion of white-matter lesions, and was independent of disease activity and steroid medication. Electrophysiological tests and cerebrospinal fluid analysis showed a higher yield of abnormality than CT scanning in cases with suspected or possible multiple sclerosis, though in such patients CT scanning excluded alternative cerebral atrophy. Modifications of the technique of CT scanning may improve the detection rate of white-matter lesions, thereby enhancing the value of CT as a diagnostic tool in the study of patients with multiple sclerosis.","Adolescent;Adrenocorticotropic Hormone/therapeutic use;Adult;Aged;Atrophy;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Diagnosis, Differential;Evoked Potentials, Auditory;Evoked Potentials, Visual;Female;Humans;Male;Middle Aged;Multiple Sclerosis/cerebrospinal fluid/*diagnosis;*Tomography, X-Ray Computed","Loizou, L. A.;Rolfe, E. B.;Hewazy, H.",1982,Oct,,0,
2838,Subcortical arteriosclerotic encephalopathy: a clinical and radiological investigation,"Subcortical arteriosclerotic encephalopathy (Binswanger's type) was diagnosed in a group of patients with hypertension or arteriosclerosis, who showed acute and subacute neurological deficits, dementia, reduced cerebral blood flow, and white matter low attenuation with mild atrophy and infarcts as the predominant CT scan features. This set of clinical and radiological criteria could be used to make the diagnosis in life, as confirmed neuropathologically in one patient.","Acute Disease;Adult;Aged;Cerebral Infarction/radiography;Cerebrovascular Circulation;Dementia/diagnosis;Demyelinating Diseases/radiography;Female;Humans;Hypertension/complications;Intracranial Arteriosclerosis/*radiography;Male;Middle Aged;Tomography, X-Ray Computed","Loizou, L. A.;Kendall, B. E.;Marshall, J.",1981,Apr,,0,
2839,Subcortical arteriosclerotic encephalopathy (Binswanger's type) and cortical infarcts in a young normotensive patient,"A 49-year-old normotensive man died after a series of strokes, slowly evolving dementia and personality change occurring over a period of 23 years. CT scan showed large infarcts involving the cortex and white matter of the temporo-occipital areas, small subcortical infarcts and low attenuation in the white matter of the frontal and parietal lobes. Neuropathological examination revealed large cortical and small subcortical infarcts corresponding to the radiological findings as well as degeneration/demyelination of central white matter corresponding to the areas of low attenuation seen on CT. The basic underlying pathological process was hyaline arteriosclerosis and atheroma which diffusely affected the small intracerebral arteries and to a lesser extent the arteries of the circle of Willis. Though unusual because of the absence of hypertension, the very early age at onset of the syndrome and the presence of large cortical infarcts this case illustrates the clinical, radiological and neuropathological features of subcortical arteriosclerotic encephalopathy (Binswanger's type).",atherosclerosis;autopsy;cardiovascular system;case report;central nervous system;computer analysis;computer assisted tomography;dementia;histology;hypertension;peripheral vascular system;personality,"Loizou, I. A.;Jefferson, J. M.;Smith, W. T.",1982,,,0,
2840,Magnetic resonance imaging-measured atrophy and its relationship to cognitive functioning in vascular dementia and Alzheimer's disease patients,"BACKGROUND: Recent pathological studies report vascular pathology in clinically diagnosed Alzheimer's disease (AD) and AD pathology in clinically diagnosed vascular dementia (VaD). We compared magnetic resonance imaging (MRI) measures of vascular brain injury (white matter hyperintensities [WMH] and infarcts) with neurodegenerative measures (medial-temporal atrophy [MTA] and cerebral atrophy [CA]) in clinically diagnosed subjects with either AD or VaD. We then examined relationships among these measures within and between the two groups and their relationship to mental status. METHODS: Semi-quantitative MRI measures were derived from blind ratings of MRI scans obtained from participants in a research clinical trial of VaD (N = 694) and a genetic epidemiological study of AD (N = 655). RESULTS: CA was similar in the two groups, but differences in the mean of MTA and WMH were pronounced. Infarcts were significantly associated with CA in VaD but not in AD; MTA and WMH were associated with CA in both. WMH was associated with MTA in both groups; however, MRI infarcts were associated with MTA in VaD but not with MTA in AD patients. MTA was strongly associated with Mini-Mental State Examination scores in both groups, whereas evidence of a modest association between WMH and Mini-Mental State Examination scores was seen in VaD patients. CONCLUSIONS: MRI data from two dementia cohorts with differing dementia etiologies find that the clinical consequences of dementia are most strongly associated with cerebral and medial-temporal atrophy, suggesting that tissue loss is the major substrate of the dementia syndrome.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/ physiopathology;Atrophy;Brain/pathology/physiopathology;Cognition Disorders/ pathology/ physiopathology;Cohort Studies;Dementia, Vascular/ pathology/ physiopathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged","Logue, M. W.;Posner, H.;Green, R. C.;Moline, M.;Cupples, L. A.;Lunetta, K. L.;Zou, H.;Hurt, S. W.;Farrer, L. A.;Decarli, C.",2011,Sep,10.1016/j.jalz.2011.01.004,0,
2841,[EEG changes in senile dementia of the Alzheimer type] EEG-Veranderungen bei seniler Demenz vom Alzheimer Typ,"Character and extent of changes in EEG in 45 patients with senile dementia of Alzheimer type (SDAT) were reported and the EEG-findings of patients with moderate (18) or severe (27) dementia were compared. The EEG-findings in these patients were compared with a group of 82 patients with multi-infarct dementia (MID). The EEG showed pathological results in 37 patients with predominating general changes (59%). In patients with severe dementia significantly more pathological results especially a significantly slower basic rhythm could be found. The degree of the cerebral atrophy verified by CT did not correspond with character and extent of the changes in EEG. The comparison between patients with SDAT and 82 patients with MID, revealed a significantly more frequent occurrence of unilateral slowing of the basic rhythm but a less frequent occurrence of focal changes. However, there was no significant difference in the number of normal and pathological EEG. The comparison between patients with SDAT and patients with MID without neurological deficit failed to show a significant difference in the number of normal and pathological EEG as well. It could be shown that in patients with severe dementia the EEG revealed significantly more pathological results as well as a significantly slower basic rhythm. However, the EEG could not differentiate between SDAT and MID.","Aged;Aged, 80 and over;Alzheimer Disease/ physiopathology;Cerebral Cortex/physiopathology;Dementia/ physiopathology;Electroencephalography;Evoked Potentials;Female;Humans;Male;Middle Aged","Logar, C.;Grabmair, W.;Schneider, G.;Lechner, H.",1987,Dec,,0,
2842,[EEG changes in senile dementia of the Alzheimer type],"Character and extent of changes in EEG in 45 patients with senile dementia of Alzheimer type (SDAT) were reported and the EEG-findings of patients with moderate (18) or severe (27) dementia were compared. The EEG-findings in these patients were compared with a group of 82 patients with multi-infarct dementia (MID). The EEG showed pathological results in 37 patients with predominating general changes (59%). In patients with severe dementia significantly more pathological results especially a significantly slower basic rhythm could be found. The degree of the cerebral atrophy verified by CT did not correspond with character and extent of the changes in EEG. The comparison between patients with SDAT and 82 patients with MID, revealed a significantly more frequent occurrence of unilateral slowing of the basic rhythm but a less frequent occurrence of focal changes. However, there was no significant difference in the number of normal and pathological EEG. The comparison between patients with SDAT and patients with MID without neurological deficit failed to show a significant difference in the number of normal and pathological EEG as well. It could be shown that in patients with severe dementia the EEG revealed significantly more pathological results as well as a significantly slower basic rhythm. However, the EEG could not differentiate between SDAT and MID.","Aged;Aged, 80 and over;Alzheimer Disease/*physiopathology;Cerebral Cortex/physiopathology;Dementia/*physiopathology;*Electroencephalography;Evoked Potentials;Female;Humans;Male;Middle Aged","Logar, C.;Grabmair, W.;Schneider, G.;Lechner, H.",1987,Dec,,0,
2843,The EEG in multiple infarctions with and without dementia,"The character and extent of changes in the EEG in 124 patients with multiple infarctions, verified by CT, were reported. Further, the EEG diagnoses of patients with (55) or without (50) accompanying dementia were compared. In 19 patients the evidence of dementia could not be defined clearly. The EEG-diagnoses in these patients were compared with a group consisting of 41 patients with primary degenerative dementia (Alzheimer). The EEG showed pathological results in 89 patients with multiple infarctions and focal abnormalities were dominant. In 55 patients with symptoms of dementia and multiple infarctions significantly more pathological EEG-reports were present than in the other patients with multiple-infarcts and a significantly slower basic rhythm could be found. In patients with neurological deficits as compared to the group without neurological symptoms and multiple infarctions the pathological changes dominated significantly. The comparison between patients with multi-infarct-dementia and 41 patients with a senile dementia of the Alzheimer type only revealed a more frequent occurrence of focal abnormalities in patients with multi-infarct-dementia. However, there was no significant difference between the number of normal pathological EEGs.",brain infarction;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;electroencephalography;human;major clinical study,"Logar, Ch;Enge, S.;Ladurner, G.",1983,,,0,
2844,Predominant left hemisphere metabolic dysfunction in dementia,"Thirty-one patients with probable Alzheimer's disease and 11 patients with memory disorders, attributable to multiple cerebral infarctions, were studied using 18-F-fluorodeoxyglucose-positron emission tomography scans. Asymmetry in cerebral glucose metabolism within these diagnostic groups was assessed by comparison with the metabolic rates obtained in age-equivalent healthy control subjects. A significantly greater number of individuals in both patient groups exhibited predominant left rather than right hemisphere hypometabolism. In addition, for patients with Alzheimer's disease, the degree of asymmetry was not related to either the severity or duration of dementia. These findings could be explained by greater susceptibility of the left hemisphere to degenerative or ischemic brain disease, by a specific sampling effect, or most likely, by greater metabolic deficits resulting from left rather than right hemisphere impairment.","Brain/*metabolism/pathology/radionuclide imaging;Cerebral Infarction/complications/metabolism;Cognition Disorders/complications/metabolism;Dementia/*metabolism/psychology/radionuclide imaging;*Functional Laterality;Humans;Magnetic Resonance Imaging;Psychiatric Status Rating Scales;Tomography, Emission-Computed","Loewenstein, D. A.;Barker, W. W.;Chang, J. Y.;Apicella, A.;Yoshii, F.;Kothari, P.;Levin, B.;Duara, R.",1989,Feb,,0,
2845,Intellectual impairment and cerebral lesions in multiple cerebral infarcts. A clinical-computed tomography study,"The relation between cerebral lesions studied by computed tomography and the dementia syndrome has been evaluated in 40 patients with multi-infarct dementia, in 44 nondemented subjects with multiple infarcts, and in 30 controls matched for age and sex. Our study of the volume of ischemic lesions showed a slightly greater loss of cerebral substance in patients with multi-infarct dementia than in nondemented subjects with multiple infarcts, particularly in subjects with unilateral focal lesions and in patients with bilateral multiple cortical and subcortical lesions. The dementia syndrome was significantly associated with multiple locations of lesions in the thalamic and cortical areas supplied by the middle cerebral arteries. Moreover, patients with the dementia syndrome showed a significantly higher degree of cerebral atrophy than nondemented subjects and controls as evaluated by measurements of ventricular size, area of ventricular space, and area of subarachnoid space.","Adult;Aged;Aged, 80 and over;Cerebral Infarction/pathology/psychology/*radiography;Dementia/pathology/*radiography;Female;Humans;Male;Middle Aged;*Tomography, X-Ray Computed","Loeb, C.;Gandolfo, C.;Bino, G.",1988,May,,0,
2846,Diagnostic evaluation of degenerative and vascular dementia,"The accuracy of the Ischemic Score (IS) of Hachinski in the differential diagnosis between senile dementia (SDAT) and multi-infarct dementia (MID) is evaluated in this study. Ninety-four demented patients were subdivided on the basis of CT scan in three subgroups: 1) CT-SDAT (ventricular enlargement and widening of cortical sulci), 2) CT-MID (multiple low density areas attributable to ischemic lesions), 3) CT-VASC (single low density area attributable to ischemic lesion). Sixty-nine percent of patients with SDAT and 94% of patients with MID had an Ischemic Score in agreement with the diagnosis established by CT scan. With the purpose of improving the accuracy of the I.S., a modified ischemic score consisting of five items (abrupt onset; history of strokes; focal symptoms; focal signs; focal (single or multiple) CT-low density areas) is proposed as a useful tool in the differential diagnosis between SDAT and MID.","Aged;Brain Ischemia/diagnosis;Cerebral Infarction/diagnosis;Dementia/*diagnosis;Diagnosis, Differential;Female;Humans;Male;Middle Aged","Loeb, C.;Gandolfo, C.",1983,May-Jun,,0,
2847,Dementia due to lacunar infarctions: a misnomer or a clinical entity?,"The following points should be considered in dealing with dementia occurring in patients with lacunar infarctions. Lacune is a pathological term and its definition rests on its size (from 2 to 15 mm in diameter). However, terms such as lacunar syndromes and lacunar infarctions are currently used in clinical parlance and recent papers. Patients with lacunar infarctions differ from patients with large infarctions, being more often hypertensive, showing a characteristic but not specific clinical syndrome, and disclosing a significantly lower recurrence rate for new episodes and a significantly higher survival rate. Patients with lacunar infarctions develop a state of dementia 5 times as often as the general population and 25 times as often as in the age group of our patients (65-69 years). Leukoaraiosis, significantly related to arterial hypertension, to lacunar infarction, to an extra risk of future stroke, may be considered an increased risk of cerebral vascular lesions possibly leading to dementia. The relationship between vascular lesions and dementia includes: the strategic location of the lesion (thalamus, corticothalamic areas, bilateral lesions); the whole cerebral hypoperfusion apart from the infarcted area, as shown by PET and SPET; remote effects of cerebral infarctions (diaschisis phenomenon); the so-called incomplete infarction; cerebral atrophy and, particularly, the enlargement of cerebral ventricles, significantly higher in patients with lacunes and dementia as compared with patients with lacunes without dementia.(ABSTRACT TRUNCATED AT 250 WORDS)","Aged;Dementia, Multi-Infarct/*diagnosis/etiology;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Prevalence;Syndrome;Tomography, Emission-Computed;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Loeb, C.",1995,,,0,
2848,Acute Parkinsonian syndrome with demyelinating leukoencephalopathy in bone marrow transplant recipients,"A syndrome of rigidity, bradykinesia, spasticity, and often myoclonus and dementia developed acutely in 5 patients who had undergone successful engraftment of bone marrow transplants for the treatment of various hematologic diseases. Magnetic resonance imaging demonstrated widespread changes in white matter; brain biopsy disclosed mild demyelination associated with active phagocytosis of myelin. One patient, who was not treated, remains severely demented. Patients treated with very high-dose methylprednisolone had complete clinical recovery.",,"Lockman, L. A.;Sung, J. H.;Krivit, W.",1991,1991,,0,
2849,White matter hyperintensities are associated with visual search behavior independent of generalized slowing in aging,"A fundamental controversy is whether cognitive decline with advancing age can be entirely explained by decreased processing speed, or whether specific neural changes can elicit cognitive decline, independent of slowing. These hypotheses are anchored by studies of healthy older individuals where age is presumed the sole influence. Unfortunately, advancing age is also associated with asymptomatic brain white matter injury. We hypothesized that differences in white matter injury extent, manifest by MRI white matter hyperintensities (WMH), mediate differences in visual attentional control in healthy aging, beyond processing speed differences. We tested young and cognitively healthy older adults on search tasks indexing speed and attentional control. Increasing age was associated with generally slowed performance. WMH were also associated with slowed search times independent of processing speed differences. Consistent with evidence attributing reduced network connectivity to WMH, these results conclusively demonstrate that clinically silent white matter injury contributes to slower search performance indicative of compromised cognitive control, independent of generalized slowing of processing speed. © 2013 Elsevier Ltd.",adult;age distribution;aged;aging;article;asymptomatic disease;controlled study;disease association;executive function;female;human;human experiment;male;nerve cell network;nervous system parameters;normal human;nuclear magnetic resonance imaging;task performance;velocity;very elderly;vision;visual disorder;white matter;white matter hyperintensity;white matter injury;young adult,"Lockhart, S. N.;Roach, A. E.;Luck, S. J.;Geng, J.;Beckett, L.;Carmichael, O.;DeCarli, C.",2014,,,0,
2850,Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging,"Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH) and fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI), differ with aging and cerebrovascular disease (CVD) and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals. © 2012 Lockhart, Mayda, Roach, Fletcher, Carmichael, Maillard, Schwarz, Yonelinas, Ranganath and DeCarli.",,"Lockhart, S. N.;Mayda, A. B. V.;Roach, A. E.;Fletcher, E.;Carmichael, O.;Maillard, P.;Schwarz, C. G.;Yonelinas, A. P.;Ranganath, C.;DeCarli, C.",2012,,,0,
2851,White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search,"The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control.",,"Lockhart, S. N.;Luck, S. J.;Geng, J.;Beckett, L.;Disbrow, E. A.;Carmichael, O.;DeCarli, C.",2015,,,0,
2852,Vascular burden and Alzheimer disease pathologic progression,"OBJECTIVE: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. METHODS: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden x time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. RESULTS: Cardiovascular risk profiles were not predictive of progression in CSF beta(4)(2)-amyloid, [(1)(8)F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. CONCLUSION: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.",Aged;Alzheimer Disease/cerebrospinal fluid/*pathology/*physiopathology;Atrophy;Brain/metabolism/pathology/physiopathology;Disease Progression;Female;Genotype;Humans;Leukoencephalopathies/*pathology/physiopathology;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Mild Cognitive Impairment/cerebrospinal fluid/pathology/physiopathology;Positron-Emission Tomography/*methods,"Lo, R. Y.;Jagust, W. J.",2012,Sep 25,10.1212/WNL.0b013e31826c1b9d,0,
2853,Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy,"Cerebral amyloid angiopathy (CAA) is a neurovascular disease that is strongly associated with an increase in the number and size of spontaneous microbleeds. Conventional methods of magnetic resonance imaging for detection of microbleeds, and positron emission tomography with Pittsburgh Compound B imaging for amyloid deposits, can separately demonstrate the presence of microbleeds and CAA in affected brains in vivo; however, there still is a critical need for strong evidence that shows involvement of CAA in microbleed formation. Here, we show in a Tg2576 mouse model of Alzheimer's disease, that the combination of histochemical staining and an optical clearing method called optical histology, enables simultaneous, co-registered three-dimensional visualization of cerebral microvasculature, microbleeds, and amyloid deposits. Our data suggest that microbleeds are localized within the brain regions affected by vascular amyloid deposits. All observed microhemorrhages (n=39) were in close proximity (0 to 144mum) with vessels affected by CAA. Our data suggest that the predominant type of CAA-related microbleed is associated with leaky or ruptured hemorrhagic microvasculature. The proposed methodological and instrumental approach will allow future study of the relationship between CAA and microbleeds during disease development and in response to treatment strategies.",,"Lo, P.;Crouzet, C.;Vasilevko, V.;Choi, B.",2016,May,10.1016/j.mvr.2016.02.002,0,
2854,Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer's disease,"Recent research on Alzheimer's disease (AD) has shown that the decline of cognitive and memory functions is accompanied by a disrupted neuronal connectivity characterized by white matter (WM) degeneration. However, changes in the topological organization of WM structural network in AD remain largely unknown. Here, we used diffusion tensor image tractography to construct the human brain WM networks of 25 AD patients and 30 age- and sex-matched healthy controls, followed by a graph theoretical analysis. We found that both AD patients and controls had a small-world topology in WM network, suggesting an optimal balance between structurally segregated and integrative organization. More important, the AD patients exhibited increased shortest path length and decreased global efficiency in WM network compared with controls, implying abnormal topological organization. Furthermore, we showed that the WM network contained highly connected hub regions that were predominately located in the precuneus, cingulate cortex, and dorsolateral prefrontal cortex, which was consistent with the previous diffusion-MRI studies. Specifically, AD patients were found to have reduced nodal efficiency predominantly located in the frontal regions. Finally, we showed that the alterations of various network properties were significantly correlated with the behavior performances. Together, the present study demonstrated for the first time that the Alzheimer's brain was associated with disrupted topological organization in the large-scale WM structural networks, thus providing the structural evidence for abnormalities of systematic integrity in this disease. This work could also have implications for understanding how the abnormalities of structural connectivity in AD underlie behavioral deficits in the patients.","Aged;Alzheimer Disease/ pathology/physiopathology;Cerebral Cortex/ pathology/physiopathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Models, Neurological;Models, Statistical;Nerve Fibers, Myelinated/pathology/physiology;Nerve Net/ pathology/physiopathology;Psychomotor Performance/physiology","Lo, C. Y.;Wang, P. N.;Chou, K. H.;Wang, J.;He, Y.;Lin, C. P.",2010,Dec 15,10.1523/jneurosci.4136-10.2010,0,
2855,"Depression in late life, cognitive decline and white matter pathology in two clinico-pathologically investigated cases","Case reports: We report two cases of late life depression who became progressively more resistant to treatment, developed cognitive impairment, and began to exhibit neurological abnormalities and evidence of vascular disease. A discussion of the clinical features of the cases is accompanied by reports of neuropathology and neuroimaging findings. Extensive white matter lesions were present on computed tomography in both patients, and basal ganglia infarcts were seen in one. Neuropathology revealed evidence of cerebral atrophy, demyelination and white matter lesions in addition to cerebrovascular and generalised vascular disease. Neither patient exhibited Alzheimer pathology outwith the norm for their age. We believe this to be the first report of neuropathological findings in depression with white matter changes. Literature review: The pathological basis of white matter lesions and their relationship to depression, its age of onset and clinical features is addressed in relation to the cases described. Pathological investigation of white matter lesions has not previously been carried out in depression and hypotheses regarding their nature in this illness are based on extrapolation from research in a variety of other disorders. The association of depression with vascular risk factors is considered, as is the relationship between depression and cognitive deficits. There is a need for further investigation in this area. Copyright © 2001 John Wiley & Sons, Ltd.",amitriptyline;antidepressant agent;fluoxetine;lithium;lofepramine;phenytoin;thioridazine;valproic acid;age;aged;Alzheimer disease;article;basal ganglion;brain atrophy;brain infarction;brain injury;case report;cerebrovascular disease;cognitive defect;computer assisted tomography;demyelination;depression;disease course;disease resistance;electroconvulsive therapy;female;human;male;pathological anatomy;risk factor;senescence;vascular disease;white matter,"Lloyd, A. J.;Grace, J. B.;Jaros, E.;Perry, R. H.;Fairbairn, A. F.;Swann, A. G.;O'Brien, J. T.;McKeith, I. G.",2001,,,0,
2856,Neurophysiological assessment of Alzheimer's disease individuals by a single electroencephalographic marker,"Here we presented a single electroencephalographic (EEG) marker for a neurophysiological assessment of Alzheimer's disease (AD) patients already diagnosed by current guidelines. The ability of the EEG marker to classify 127 AD individuals and 121 matched cognitively intact normal elderly (Nold) individuals was tested. Furthermore, its relationship to AD patients' cognitive status and structural brain integrity was examined. Low-resolution brain electromagnetic tomography (LORETA) freeware estimated cortical sources of resting state eyes-closed EEG rhythms. The EEG marker was defined as the ratio between the activity of parieto-occipital cortical sources of delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms. Results showed 77.2% of sensitivity in the recognition of the AD individuals; 65% of specificity in the recognition of the Nold individuals; and 0.75 of area under the receiver-operating characteristic curve. Compared to the AD subgroup with the EEG maker within one standard deviation of the Nold mean (EEG-), the AD subgroup with EEG+ showed lower global cognitive status, as revealed by Mini-Mental State Evaluation score, and more abnormal values of white-matter and cerebrospinal fluid normalized volumes, as revealed by structural magnetic resonance imaging. We posit that cognitive and functional status being equal, AD patients with EEG+ should receive special clinical attention due to a neurophysiological ""frailty"". EEG+ label can be also used in clinical trials (i) to form homogeneous groups of AD patients diagnosed by current guidelines and (ii) as end-point to evaluate intervention effects.",,"Lizio, R.;Del Percio, C.;Marzano, N.;Soricelli, A.;Yener, G. G.;Basar, E.;Mundi, C.;De Rosa, S.;Triggiani, A. I.;Ferri, R.;Arnaldi, D.;Nobili, F. M.;Cordone, S.;Lopez, S.;Carducci, F.;Santi, G.;Gesualdo, L.;Rossini, P. M.;Cavedo, E.;Mauri, M.;Frisoni, G. B.;Babiloni, C.",2015,,10.3233/jad-143042,0,
2857,Leukoencephalopathy with calcifications and cysts: A purely neurological disorder distinct from coats plus,"Objective With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. Patients and Methods A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. Results The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. Conclusion LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined. © 2014 Georg Thieme Verlag KG Stuttgart New York.",conserved telomere maintenance component 1;protein;unclassified drug;adolescent;adult;article;basal ganglion;brain calcification;brain region;brain stem;caudate nucleus;cerebellum;child;clinical article;coat plus disease;cognitive defect;computer assisted tomography;contrast enhancement;deep gray matter;deep gyri;deep white matter;dentate nucleus;developmental disorder;female;genetic disorder;globus pallidus;human;infant;leukoencephalopathy with calcification and cyst;male;mental deterioration;motor dysfunction;myelination;neurologic disease;neuroradiology;newborn;nuclear magnetic resonance imaging;priority journal;putamen;seizure;subcortex;thalamus,"Livingston, J. H.;Mayer, J.;Jenkinson, E.;Kasher, P.;Stivaros, S.;Berger, A.;Cordelli, D. M.;Ferreira, P.;Jefferson, R.;Kutschke, G.;Lundberg, S.;Ounap, K.;Prabhakar, P.;Soh, C.;Stewart, H.;Stone, J.;Van Der Knaap, M. S.;Van Esch, H.;Van Mol, C.;Wakeling, E.;Whitney, A.;Rice, G. I.;Crow, Y. J.",2014,,,0,
2858,Myelin degrading activity in the CSF of HIV-1-infected patients with neurological diseases,"Degradation of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination.",myelin basic protein;adult;article;cerebrospinal fluid;clinical article;controlled study;dementia;demyelination;female;human;Human immunodeficiency virus;leukoencephalopathy;male;nuclear magnetic resonance imaging;priority journal,"Liuzzi, G. M.;Mastroianni, C. M.;Fanelli, M.;Massetti, A. P.;Vullo, V.;Delia, S.;Riccio, P.",1994,,,0,
2859,Vascular cognitive impairment and aerobic exercise: A 6-month randomized controlled trial,"Background: Worldwide, vascular cognitive impairment (VCI) is the second most common etiology contributing to cognitive impairment among older adults. Yet, VCI may be the most treatable form of cognitive impairment as many of its risk factors can be reduced with exercise. Nevertheless, few randomized controlled trials to date have specifically assessed the efficacy of exercise training on cognitive function in this high-risk group. Thus, we conducted a 6-month proof-of-concept randomized controlled trial of thriceweekly aerobic exercise training (AE) among adults with mild sub-cortical ischemic VCI (SIVCI). Methods: Seventy-one adults (56-96 years) with SIVCI were recruited and randomized (1:1) to one of two experimental groups: 1) 3x/week AE or 2) usual care (UC). SIVCI was confirmed by: 1) evidence of subcortical white matter lesions from neuroimaging (i.e., CT or MRI); 2) a score of less than 26 on the Montreal Cognitive Assessment (MoCA); and 3) clinical assessment by neurologist. The primary outcome for this study was the Alzheimer's Disease Assessment Scale (ADAS-Cog). The AE classes were 60 minutes in duration and led by certified fitness instructors. Target heart rates were determined by the Karvonen formula. Participants of the UC group received an education seminar on nutrition once per month. Between- group differences in ADAS-Cog at trial completion was determined by analysis of covariance, with baseline ADASCog and baseline MoCA score included as covariates. Results: At trial completion, 62 of the 71 participants completed the trial. There were 2 drop outs from AE group and 7 from the UC group. Two additional individuals from the AE group were excluded from analyses due to medical reasons: 1 due to terminal and aggressive brain tumor and 1 due to rapid decline in overall function (likely due to mixed dementia). Compared with the UC group, participants in the AE group significant improved their cognitive function, as measured by the ADAS-Cog (p < 0.05). We also observed significant between-group differences in the Six-Minute Walk Test, providing evidence of treatment fidelity. Conclusions: AE may be an efficacious approach to improve cognitive function among individuals with mild SIVCI, and thereby, may prolong their functional independence and quality of life. (Table Presented).",cognitive defect;aerobic exercise;human;randomized controlled trial;cognition;exercise;adult;date (fruit);heart rate;fitness;risk factor;clinical assessment;randomized controlled trial(topic);neuroimaging;Montreal cognitive assessment;independence;etiology;brain tumor;neurologist;white matter lesion;analysis of covariance;high risk population;nutrition;education;dementia;quality of life;nuclear magnetic resonance imaging;Alzheimer Disease Assessment Scale,"Liu-Ambrose, T.;Davis, J.;Best, J. R.;Eng, J. J.;Lee, P. E.;Jacova, C.;Munkacsy, M.;Boyd, L.;Hsiung, G. Y.",2015,,,0,
2860,Influencing factors of intellectual impairment in cerebral infarct patients,"Aim: To study the influencing factors of intellectual impairment in cerebral infarct patients. Methods: The intelligence levels of 249 cerebral infarct patients identified by CT findings who were hospitalized in the Department of Neurology, Renmin Hospital of Wuhan, University from January 1996 to October 1998 were tested by Hasegawa Dementia Scale scored 0 to 21.5 as intellectual impairment group and 22 to 32.5 as non-intellectual impairment group. The correlation of the occurrence of intellectual impairment with sex, age, education level, major risk of stroke (hypertension and diabetes), cerebral atrophy, leukoaraiosis (LA), and size and quantity of focal infarct was analyzed. Results: Among 249 cases of cerebral infarction, 106 (42.6%) had intellectual impairment. The intellectual impairment was correlated with age, sex, education level, hypertension and diabetes.. More and larger focal infarcts resulted in higher incidence of intellectual impairment. Cerebral atrophy and LA were closely correlated with intellectual impairment. Conclusion: Interaction among multiple factors after cerebral infarction results in intellectual impairment, and intellectual impairment are correlated with many factors, including quantity and size of focal infarct, cerebral atrophy, LA, etc.",adult;age;aged;article;brain atrophy;brain infarction;brain infarction size;China;computer assisted tomography;controlled study;correlation function;diabetes mellitus;education;female;human;hypertension;incidence;intellectual impairment;intelligence;leukoaraiosis;major clinical study;male;risk assessment;risk factor;scoring system;sex;cerebrovascular accident,"Liu, Z. C.;Li, T.;Pan, S. Q.",2005,,,0,
2861,Magnetic resonance spectroscopy study of amnestic mild cognitive impairment and vascular cognitive impairment with no dementia,"Amnestic mild cognitive impairment (aMCI) and vascular cognitive impairment with no dementia (VCIND) are highly predictive of Alzheimer's disease and vascular dementia. In this study, a 2-dimensional magnetic resonance spectroscopy was performed in 25 patients with aMCI, 28 patients with VCIND, and 32 normal controls (NCs). The concentrations of N-acetyl aspartate (NAA), choline (Cho), myoinositol (MI), and creatine (Cr) were measured, and their ratios were calculated. The patients with aMCI displayed significantly lower NAA/MI bilaterally in the posterior cingulate gyrus (PCG) and white matter of occipital lobe (OLWM) than NC participants or patients with VCIND , whereas patients with VCIND displayed markedly lower NAA/Cho bilaterally in the white matter of frontal lobe (FLWM) and left OLWM, and right dorsal thalamus (DT) than patients with NC or aMCI. Compared with the controls, patients with aMCI displayed lower NAA and NAA/Cr in bilateral PCG, left precuneus, and DT, whereas patients with VCIND displayed lower NAA/Cr in bilateral DT and FLWM. In addition, increased MI in right PCG of patients with aMCI and increased Cho in left FLWM of patients with VCIND were also observed. The results might help guide a clinical differentiation between the 2 disorders. © The Author(s) 2013.",choline;creatine;inositol;n acetylaspartic acid;aged;article;brain metabolism;cognitive defect;controlled study;female;frontal lobe;human;major clinical study;male;mild cognitive impairment;Mini Mental State Examination;nuclear magnetic resonance scanner;occipital lobe;posterior cingulate;precuneus;proton nuclear magnetic resonance;thalamus;vascular cognitive impairment with no dementia;white matter;Signa,"Liu, Y. Y.;Yang, Z. X.;Shen, Z. W.;Xiao, Y. Y.;Cheng, X. F.;Chen, W.;Chen, Y. W.;Wu, R. H.",2014,,,0,
2862,Serum Aβ is Predictive for Short-Term Neurological Deficits After Acute Ischemic Stroke,"Mounting evidence suggests that ischemic stroke (IS) is associated with Alzheimer’s disease (AD). IS and vascular risk factors increase the risk for AD. However, whether AD pathologies exist in IS and the effects of these pathologies on stroke remain unknown. In the present study, we aimed to investigate the alterations of serum Aβ after acute IS (AIS), and its correlations with the neurological deficits, infarction volume, and site after stroke. AIS patients (n = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD patients (n = 48) and cognitively normal controls (NC, n = 37) were also enrolled. Serum Aβ40 and Aβ42 and the National Institute of Health Stroke Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found that serum Aβ40 and Aβ42 levels were increased at day 1 and reached peak levels at day 3, and decreased to pre-stroke levels at day 7. Serum Aβ40 levels at day 1 were correlated with the NIHSS scores and infarction volume of AIS patients. Serum Aβ42 levels at day 1 were significantly higher in IS patients with dominant gray matter infarction. Serum Aβ40 levels at day 1 were predictive for NIHSS at day 7. Our results indicate that AIS can induce the generation of Aβ in the brain, which may in turn be involved in the pathogenesis of neurological deficits after stroke. Serum Aβ might be predictive for the short-term neurological deficits after AIS.",12001966;amyloid beta protein[1-40];amyloid beta protein[1-42];adult;age distribution;aged;Alzheimer disease;article;blood analysis;brain infarction size;brain ischemia;controlled study;demography;disease association;disease course;educational status;female;gray matter;human;major clinical study;male;neuroimaging;nuclear magnetic resonance imaging;prediction;priority journal;protein blood level;sex difference,"Liu, Y. H.;Cao, H. Y.;Wang, Y. R.;Jiao, S. S.;Bu, X. L.;Zeng, F.;Wang, Q. H.;Li, J.;Deng, J.;Zhou, H. D.;Wang, Y. J.",2015,,,0,
2863,Retinal arterial abnormalities correlate with brain white matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy,"PURPOSE: The aim of this study is to determine the relationship between retinal abnormalities and brain white matter hyper-intensities (WMH) in symptomatic patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). METHODS: Fifteen patients with CADASIL and fifteen age-matched healthy control individuals were enrolled in this study. Ophthalmological examinations were performed on all subjects and all patients with CADASIL underwent cerebral MRI scanning. Retinal artery abnormalities were graded according to the Keith-Wagener-Barker hypertensive retinopathy classification. WMH were classified as punctuate (Grade 1), nodular or early confluent (Grade 2) and diffusly confluent (Grade 3). Partial correlation was used to assess the relationship between retinal abnormalities and WMH, controlling for age. RESULTS: Retinal arteriole narrowing existed in 15 cases and 2 controls, with Grade 2 and Grade 3 being the most common grading of retinal artery narrowing in patients with CADASIL. All patients had WMH on MRI, rated as Grade 1 in one patient, Grade 2 in five patients and Grade 3 in nine patients. The correlation coefficient of retinal arteriole narrowing and WMH was 0.546 (P < 0.05). CONCLUSION: Retinal arteriole narrowing may be associated with the severity of the cerebral lesions in CADASIL.",Adult;Arterioles/abnormalities;Brain/*pathology;CADASIL/*complications/*diagnosis;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Retinal Artery/*abnormalities/pathology,"Liu, Y.;Wu, Y.;Xie, S.;Luan, X. H.;Yuan, Y.",2008,Aug,10.1111/j.1442-9071.2008.01825.x,0,
2864,Diffusion tensor imaging and tract-based spatial statistics in Alzheimer's disease and mild cognitive impairment,"We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Brain Mapping/methods/statistics & numerical data;Diffusion Tensor Imaging/ methods/statistics & numerical data;Female;Humans;Image Processing, Computer-Assisted/methods/statistics & numerical data;Male;Mild Cognitive Impairment/ diagnosis;Severity of Illness Index","Liu, Y.;Spulber, G.;Lehtimaki, K. K.;Kononen, M.;Hallikainen, I.;Grohn, H.;Kivipelto, M.;Hallikainen, M.;Vanninen, R.;Soininen, H.",2011,Sep,10.1016/j.neurobiolaging.2009.10.006,0,
2865,Inclusion-positive cell types in adult-onset intranuclear inclusion body disease: Implications for clinical diagnosis,"The distribution of inclusions in adult-onset type intranuclear inclusion body disease (INIBD) has not been fully described. We analyzed the clinical and pathological changes of three autopsy cases of adult type INIBD and provide a detailed description of the distribution of inclusions in nervous system and visceral organs. Although patients showed cognitive decline and autonomic dysfunction, there were no specific symptoms related to general organs. The neuropathological changes responsible for cognitive decline and autonomic dysfunction were considered to be white matter changes in the cerebral hemispheres and inclusions in the autonomic nervous system, e.g., in the sympathetic ganglia and myenteric plexus. Alterations of spongiosis with both myelin and axon loss in the cerebral white matter seemed to be related to dysfunction of astrocytes with intranuclear inclusions. In visceral organs, the inclusions were much more widely distributed than previously appreciated and included renal mesangial cells, adrenal sustentacular cells, fibrocytes, Kupffer cells, pancreatic centroacinar and ductal epithelial cells. Since skeletal muscle cells, Schwann cells and smooth muscle cells were also inclusion positive, we propose that biopsy of muscle, peripheral nerve or rectum may prove useful for the clinical diagnosis of INIBD. © Springer-Verlag 2008.",adult;Alzheimer disease;article;ataxia;autonomic dysfunction;autonomic nervous system;Binswanger encephalopathy;case report;cell nucleus inclusion body;clinical feature;cognitive defect;computer assisted tomography;dementia;dysarthria;electron microscopy;epithelium cell;female;hemiplegia;hemisphere;histopathology;human;human cell;human tissue;immunohistochemistry;intranuclear inclusion body disease;Kupffer cell;leukoencephalopathy;male;mesangium cell;mortality;multiple organ failure;myenteric plexus;neuropathology;nuclear magnetic resonance imaging;onset age;parkinsonism;peripheral nerve;pneumonia;priority journal;Schwann cell;skeletal muscle;smooth muscle fiber;sympathetic ganglion;white matter,"Liu, Y.;Mimuro, M.;Yoshida, M.;Hashizume, Y.;Niwa, H.;Miyao, S.;Ujihira, N.;Akatsu, H.",2008,,,0,
2866,"Lymphomatosis cerebri: clinical features, imaging characteristics and neuropathological findings","Objective: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma without evidence of a mass lesion. There was no case report in China.We reported our case and reviewed the related literature for early diagnosis and appropriate treatments. Methods: Clinical and imaging data, neuropathology results and therapeutic reaction of a patient diagnosed as LC were reviewed retrospectively. Results: A 53-year-old woman presented with 6 months of rapidly progressive dementia, personality change and lethargy. Neurological examination showed globally cognitive deficits and bilateral positive Babisnki's sign. Brain magnetic resonance imaging revealed diffuse bilateral white matter changes in the cerebral hemispheres and involvement of the brainstem, basal ganglia and thalamus, with needle-like enhancement. Sterotactic biopsy specimen showed diffuse infiltration of B-type malignant lymphoid cells, consistent with LC. Conclusions: Corticosteroids could temporarily alleviate symptoms and lesions of LC. Brain biopsies should be early performed for the prompt diagnosis and effective treatment.",adult;article;basal ganglion;brain stem;case report;central nervous system tumor;clinical feature;cognitive defect;dementia;disease course;disease duration;early diagnosis;female;hemisphere;human;human tissue;lethargy;lymphoid cell;lymphomatosis;lymphomatosis cerebri;middle aged;neuroimaging;neurologic examination;neuropathology;nuclear magnetic resonance imaging;personality disorder;thalamus;treatment planning;white matter lesion,"Liu, X.;Lu, D.;Wang, X.;Li, S.;Liu, Y.;Pang, Z.;Xu, S.;Wang, Z.;Wang, J.;Wang, G.;Du, Y.",2016,,10.3760/cma.j.issn.1006-7876.2016.10.005,0,
2867,76-space analysis of grey matter diffusivity: methods and applications,"Diffusion Weighted Imaging (DWI) and Diffusion Tensor Imaging (DTI) are widely used in the study and diagnosis of neurological diseases involving the White Matter (WM). However, many neurological and neurodegenerative diseases (e.g., Alzheimer's disease and Creutzfeldt-Jakob disease) are generally considered to involve the Grey Matter (GM). Investigation of GM diffusivity of normal aging and pathological brains has both scientific significance and clinical applications. Most of previous research reports on quantification of GM diffusivity were based on the manually labeled Region of Interests (ROI) analysis of specific neuroanatomic regions. The well-known drawbacks of ROI analysis include inter-rater variations, irreproducible results, tediousness, and requirement of a priori definition of interested regions. In this paper, we present a new framework of automated 76-space analysis of GM diffusivity using DWI/DTI. The framework will be evaluated using clinical data, and applied for study of normal brain, Creutzfeldt-Jakob disease and Schizophrenia.","Algorithms;Brain/ anatomy & histology;Diffusion Magnetic Resonance Imaging/methods;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Neuroglia/ cytology;Neurons/ cytology","Liu, T.;Young, G.;Huang, L.;Chen, N. K.;Wong, S. T.",2005,,,0,
2868,Limited relationships between two-year changes in sulcal morphology and other common neuroimaging indices in the elderly,"Measuring the geometry or morphology of sulcal folds has recently become an important approach to investigating neuroanatomy. However, relationships between cortical sulci and other brain structures are poorly understood. The present study investigates how age-related changes in sulcal width are associated with age-related changes in traditional indices of brain structure such as cortical thickness, and cortical gray matter (GM), white matter (WM), subcortical, and white matter hyperintensity (WMH) volumes. These indices and sulcal width were measured at baseline and at two-year follow up in 185 community-dwelling individuals (91 men) aged 70-89. years. There were significant increases in sulcal width and WMH volume, and significant decreases in all other indices between baseline and follow-up. Sulcal widening was associated with decreases in cortical GM, subcortical and WM volumes. A further association between sulcal width and cortical thickness became non-significant when cortical GM volume was controlled for. Our findings give insights into the mechanisms responsible for cortical sulcal morphology. The relationships between sulcal morphology and other common measures suggest that it could be a more comprehensive measure for clinical classifications than traditional neuroimaging metrics, such as cortical thickness. © 2013 Elsevier Inc.",aged;aging;article;brain cortex;brain radiography;brain size;brain sulcus;community;cortical gray matter;cortical thickness;follow up;gray matter;human;longitudinal study;neuroimaging;nuclear magnetic resonance scanner;priority journal;subcortex;thickness;white matter;white matter hyperintensity,"Liu, T.;Sachdev, P. S.;Lipnicki, D. M.;Jiang, J.;Geng, G.;Zhu, W.;Reppermund, S.;Tao, D.;Trollor, J. N.;Brodaty, H.;Wen, W.",2013,,,0,
2869,The Association Between Retinal Neuronal Layer and Brain Structure is Disrupted in Patients with Cognitive Impairment and Alzheimer's Disease,"Both healthy and pathological aging due to Alzheimer's disease (AD) are associated with decreased brain grey matter volume (GMV) and disrupted white matter (WM) microstructure. Thinner macular ganglion cell-inner plexiform layer (GC-IPL) measured by spectral-domain optical coherence tomography has been reported in patients with AD and mild cognitive impairment. Emerging evidence suggested a link between thinner GC-IPL and lower GMV in subjects with no dementia using region-of-interest-based approach. However, it remains unknown whether GC-IPL thickness is associated with brain WM microstructure and how such association differed between normal and cognitively impaired subjects. Here, for subjects with no cognitive impairment (NCI), thinner GC-IPL was associated with lower WM microstructure integrity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tracts, anterior thalamic radiation, and cingulum regions, while it was weakly associated with lower GMV in visual cortex and cerebellum. Nevertheless, these retina-brain associations were disrupted in the presence of cognitive impairment. Correlations between GMV and GC-IPL were lost in patients with cognitive impairment but no dementia (CIND) and AD patients. GC-IPL was related to WM microstructural disruption in similar regions with decreased significance. In contrast, lower WM microstructure integrity in the fornix showed a trend of correlation with thinner GC-IPL in both CIND and AD but not NCI. Collectively, our findings suggest the possible physiological retina-brain relationship in healthy aging, which might be disrupted by disease-induced changes in patients with cognitive impairment. Longitudinal study with larger patient sample should follow to confirm the disease mechanism behind these retina-brain relationship changes.",Alzheimer disease;diffusion tensor imaging;mild cognitive impairment;optical coherence tomography;retinal ganglion cells;white matter,"Liu, S.;Ong, Y. T.;Hilal, S.;Loke, Y. M.;Wong, T. Y.;Chen, C. L.;Cheung, C. Y.;Zhou, J.",2016,Sep 6,10.3233/jad-160067,0,
2870,"White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia","Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.",cholinergic system;cognitive impairment;magnetic resonance imaging;tractography;vascular cognitive impairment no dementia,"Liu, Q.;Zhu, Z.;Teipel, S. J.;Yang, J.;Xing, Y.;Tang, Y.;Jia, J.",2017,,,0,
2871,White matter changes in patients with amnestic mild cognitive impairment detected by diffusion tensor imaging,"Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer's disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.",Aged;Amnesia/ complications;Brain/ pathology/physiopathology;Case-Control Studies;Corpus Callosum/pathology/physiopathology;Diffusion Tensor Imaging;Female;Humans;Limbic System/parasitology/pathology;Male;Middle Aged;Mild Cognitive Impairment/ complications/diagnosis/ pathology/physiopathology;Nerve Net/pathology/physiopathology,"Liu, J.;Yin, C.;Xia, S.;Jia, L.;Guo, Y.;Zhao, Z.;Li, X.;Han, Y.;Jia, J.",2013,,10.1371/journal.pone.0059440,0,
2872,White Matter Abnormalities in Two Different Subtypes of Amnestic Mild Cognitive Impairment,"White matter (WM) degeneration has been found during the course of cognitive decline in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), however, it is unclear whether there are different WM microstructural abnormalities between two subtypes of aMCI, including single domain aMCI (aMCI-s) and multiple domain aMCI (aMCI-m). Thirty-two patients of aMCI single-domain (aMCI-s), twenty-three patients of aMCI multiple-domain (aMCI-m) and twenty-three healthy normal controls (NC) participated in this study. Neuropsychological measures and diffusion tensor imaging (DTI) data were acquired from each subject and tract-based spatial statistics (TBSS) was implemented. It was found that both aMCI groups showed significantly reduced fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF) than NC. It was also identified that, as compared to aMCI-m, aMCI-s showed significantly decreased FA in the left SLF, left uncinate fasciculus (UF) and left inferior longitudinal fasciculus (ILF), while significantly increased FA in the left anterior thalamic radiation (ATR). The correlation analysis showed that FA values in the regions with group difference were significantly correlated with cognitive functions as measured by Boston naming test and trail making test. These results suggested that the variations of aMCI may be differentiated by FA indexes and DTI may help to understand why specific signs and symptoms occur in patients.",,"Liu, J.;Liang, P.;Yin, L.;Shu, N.;Zhao, T.;Xing, Y.;Li, F.;Zhao, Z.;Li, K.;Han, Y.",2017,,,0,
2873,Racial differences in gray matter integrity by diffusion tensor in black and white octogenarians,"Objective: To quantify racial differences in brain structural characteristics in white and black octogenarians, and to examine whether these characteristics contribute to cognition. Methods: Cross-sectional study of 283 adults 79-89 years old (59.4% white;42.0% women) with data on gray matter integrity via diffusion tensor imaging (mean diffusivity), gray matter atrophy (GMA), white matter hyperintensities (WMH), literacy, smoking, drinking, income, hypertension and diabetes. Participants were recruited from an ongoing epidemiological study of older adults living in the community with a range of chronic conditions, physical and cognitive function. Standardized betas (sbeta) of neuroimaging markers predicting Digit Symbol Substitution Test (DSST) and Modified Mini-Mental State Examination (3MS) scores were computed in multivariable regression models stratified by race. Results: Compared to whites, blacks had lower DSST (p=0.001) and lower 3MS (p=0.006), but also lower mean diffusivity (i.e. higher gray matter microstructural integrity, p=0.032), independent of gender, income, literacy, body mass index, diabetes and drinking habits. Racial differences were not significant for WMH (p=0.062) or GMA (p=0.4). Among blacks, mean diffusivity and WMH were associated with DSST (sbeta=-.209, p=0.037and -.211, p=.038, respectively) independent of each other and other covariates; among whites, mean diffusivity, but not WMH, was significantly associated with DSST and 3MS (sbeta =-.277, p=.002 and -.250, p=0.029, respectively). Conclusions: In this cohort of octogenarians living in the community, blacks appeared to have higher microstructural integrity of gray matter as compared to whites. This neuroimaging marker was related to higher cognition even in the presence of WMH and other cardiovascular conditions. If confirmed, these findings suggest microstructural gray matter integrity may be a target to improve cognition, especially among blacks who survive to very old age with a range of chronic cardiovascular conditions.",aged;Black person;body mass;brain atrophy;Caucasian;cognition;conference paper;controlled clinical trial;controlled study;diabetes mellitus;diffusion tensor imaging;digit symbol substitution test;drinking;drinking behavior;female;gender;gray matter;gray matter atrophy;human;hypertension;income;major clinical study;male;Mini Mental State Examination;nuclear magnetic resonance scanner;priority journal;race difference;reading;smoking;very elderly;white matter hyperintensity,"Liu, G.;Allen, B.;Lopez, O.;Aizenstein, H.;Boudreau, R.;Newman, A.;Yaffe, K.;Kritchevsky, S.;Launer, L.;Satterfield, S.;Simonsick, E.;Rosano, C.",2015,,,0,
2874,Disrupted white matter integrity is associated with cognitive deficits in patients with amnestic mild cognitive impairment: An atlas-based study,"OBJECTIVE: This study investigated white matter integrity in patients with amnestic mild cognitive impairment by diffusion tensor imaging. METHODS: A total of 83 patients with amnestic mild cognitive impairment and 85 elderly healthy controls underwent neuropsychological testing and a diffusion tensor imaging scan. Whole-brain white matter data were parcellated into 50 regions based on the anatomical ICBM-DTI-81 atlas, and regional diffusion metrics consisting of fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were calculated for each region. Diffusion tensor imaging indices were compared between groups, and it was determined that between-group differences were significantly correlated with neurocognitive performance. RESULTS: Relative to the healthy controls group, the amnestic mild cognitive impairment group exhibited poorer cognitive performance in all neuropsychological tests except the complex figure test (p = 0.083) and showed decreased mean fractional anisotropy in the fornix, increased mean diffusivity in the fornix and bilateral uncinate fasciculus, elevated axial diffusivity in the fornix and genu of corpus callosum, and elevated radial diffusivity in the fornix and bilateral uncinate fasciculus (p < 0.05). Behaviorally, integrity of the bilateral uncinate fasciculus was correlated positively with episodic memory function, while left uncinate fasciculus integrity was positively associated with language function in the amnestic mild cognitive impairment group (p < 0.05). CONCLUSION: White matter abnormalities in neural pathways associated with memory were correlated with neurocognitive deficiencies in amnestic mild cognitive impairment. Given that amnestic mild cognitive impairment is putatively a prodromal syndrome for Alzheimer's disease, this study furthers our understanding of the white matter changes associated with Alzheimer's disease pathogenesis in the predementia stage.",Amnestic mild cognitive impairment;atlas-based analysis;cognitive function;diffusion tensor imaging,"Liu, D.;Wang, Z.;Shu, H.;Zhang, Z.",2016,,10.1177/2050312116648812,0,
2875,White matter change in diffusion tensor imaging of amnestic mild cognitive impairment,"Objective: To investigate the features of white matter impairment and its relationship with cognition in patients with amnestic mild cognitive impairment (aMCI). Methods: Eighty-three cases of aMCI and 85 normal aging volunteers were scanned with diffusion tensor imaging (DTI) using MR system. All subjects completed the neuropsychological battery. We analyzed the differences between two groups using tract-based spatial statistics and the association between regions in difference and cognition using correlation analysis. Results: There were significant differences between aMCI and normal control in the neuropsychological battery including the Mini-Mental State Examination(26.2 ± 2.6 vs 28.3 ± 1.3, F = 43.224, P = 0.000), Mattis Dementia Rating Scale-2 (131.4 ± 6.9 vs 138.0 ± 3.5, F = 62.308, P = 0.000), Auditory Verbal Learning Test -delayed recall(2.4 ± 1.6 vs 1.5 ± 2.0, F = 324.018, P =0.000), Boston Naming Test (8.7 ± 1.4 vs 9.2 ± 1.0, F = 6.821, P = 0.010), Rey-Osterrich Complex Figure Test (12.1 ± 7.3 vs 18.5 ± 6.1, F=40.674, P=0.000), Symbol Digit Modulation Test(30.0 ± 10.1 vs 38.6 ± 9.8, F = 30.786, P = 0.000), Trail-Making Test Part B ((256.8 ± 124.5) s vs (178.1 ± 59.0)s, F = 27.601, P = 0.000). Significantly higher diffusivity indexes and radial diffusivity were also found in aMCI subjects compared to healthy elders in the parahippocampal, superior longitudinal fasciculus, inferior longitudinal fasciculus, superior fronto-occipital fasciculus, inferior fronto-occipital fasciculus, unciform fasciculus, corticospinal tract, corpus callosum, cingulum, corona radiate. We also found that axial diffusivity was significantly increased in the parahippocampal, superior longitudinal fasciculus, inferior longitudinal fasciculus, superior fronto-occipital fasciculus, inferior fronto-occipital fasciculus, unciform fasciculus, corticospinal tract and corpus callosum, whereas fractional anisotropy changes were not observed in aMCI. Diffusivity indexes values in bilateral frontal lobe (left r = 0.67; right r = 0.70), left cingulum (r = 0.63), parietal white matter (r = 0.69) and radial diffusivity values in left parietal (r = 0.68) were significantly related to Trail Making Test A among aMCI (all P < 0.05). Conclusions: In aMCI patients, there was a wide range of white matter damage, with no brain region-specific. Executive function deficit was related to the white matter impairment in bilateral frontal lobe, left cingulate and parietal lobe. The specificity and sensitivity of four DTI parameters fordetecting white matter lesions are variant. Copyright © 2014 by the Chinese Medical Association.",,"Liu, D.;Shu, H.;Wang, Z.;Yue, C.;Shi, Y.;Xie, C.;Zhang, Z.",2014,May,,0,
2876,Complexity and synchronicity of resting state blood oxygenation level-dependent (BOLD) functional MRI in normal aging and cognitive decline,"PURPOSE: To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in normal aging and cognitive decline associated with familial Alzheimer's disease (fAD). MATERIALS AND METHODS: Resting state BOLD fMRI data were acquired at 3T from two independent cohorts of subjects consisting of healthy young (age 23 +/- 2 years, n = 8) and aged volunteers (age 66 +/- 3 years, n = 8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2 +/- 15.8 years; and eight nonmutation carrying family members, age 28.8 +/- 5.9 years). Mean ApEn values were compared between the two age groups and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. RESULTS: Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. CONCLUSION: ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases.","Aged, 80 and over;Aging/ physiology;Brain Mapping/ methods;Cerebral Cortex/ physiology;Connectome/methods;Cortical Synchronization/ physiology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Nerve Net/ physiology;Oxygen/ blood;Young Adult","Liu, C. Y.;Krishnan, A. P.;Yan, L.;Smith, R. X.;Kilroy, E.;Alger, J. R.;Ringman, J. M.;Wang, D. J.",2013,Jul,10.1002/jmri.23961,0,
2877,A quantitative MRI study of vascular dementia,"We studied the MRI and clinical factors associated with dementia following stroke by quantifying ventricle-to-brain ratio (VBR), anatomic region of infarction, and cortical, subcortical, and white matter areas of infarction in 24 stroke patients with dementia and 29 nondemented stroke patients. The factors that most strongly correlated with dementia were total white matter lesion (WML) area, left WML, VBR, right WML, age, left cortical infarction area, left parietal infarction area, and total infarction area. Using discriminant analysis, these factors correctly classified 28 of 29 nondemented patients and 18 of 24 demented patients. Both cortical and white matter total infarction area measurements were strongly associated with dementia in stroke patients, suggesting that these factors strongly influenced the development of dementia following stroke. There was a strong association between dementia and left- but not right-hemisphere infarction area. The only demographic factor that strongly associated with dementia was age.","Aged;Brain/pathology;Cerebral Cortex/pathology;Cerebral Infarction/diagnosis;Cerebral Ventricles/pathology;Cerebrovascular Disorders/complications/diagnosis;Dementia, Vascular/complications/*diagnosis/psychology;Discriminant Analysis;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales","Liu, C. K.;Miller, B. L.;Cummings, J. L.;Mehringer, C. M.;Goldberg, M. A.;Howng, S. L.;Benson, D. F.",1992,Jan,,0,
2878,Characterizing brain iron deposition in subcortical ischemic vascular dementia using susceptibility-weighted imaging: An in vivo MR study,"The aim of this study was to investigate the brain iron accumulation in subcortical ischemic vascular dementia (SIVD) and its correlation with the severity of cognitive impairment. Thirty five patients with SIVD and 35 healthy controls underwent high-resolution susceptibility-weighted imaging. The phase shift value of the bilateral hippocampus (HP), caudate nucleus (CN), globus pallidus (GP), putamen (PU), thalamus (TH), red nucleus (RN), substantia nigra (SN), anterior cingulate cortex (ACC), posterior cingulate (PCC), parietal cortex (PC) and frontal white matter (FWM) were examined and correlated with neuropsychological scores for SIVD patients. They exhibited significant increased phase shift values in the bilateral HP, CN, PU, right GP and left SN (P<0.05). Close correlations were found between the phase shift value of the left HP, right CN and neuropsychological scores. Our results suggest that brain iron deposition may be a biomarker of SIVD and play an important role in the pathophysiological mechanism.","Aged;Biomarkers/metabolism;Brain/ metabolism;Brain Ischemia/metabolism/psychology;Cognition Disorders/metabolism;Dementia, Vascular/ metabolism/psychology;Female;Humans;Iron/ metabolism;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests","Liu, C.;Li, C.;Yang, J.;Gui, L.;Zhao, L.;Evans, A. C.;Yin, X.;Wang, J.",2015,Jul 15,10.1016/j.bbr.2015.04.003,0,
2879,Vitamin D and Risk of Neuroimaging Abnormalities,"Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged >/=65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (>/=25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (>/=50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants.",,"Littlejohns, T. J.;Kos, K.;Henley, W. E.;Lang, I. A.;Annweiler, C.;Beauchet, O.;Chaves, P. H.;Kestenbaum, B. R.;Kuller, L. H.;Langa, K. M.;Lopez, O. L.;Llewellyn, D. J.",2016,,10.1371/journal.pone.0154896,0,
2880,Enhanced rapid-onset cortical plasticity in CADASIL as a possible mechanism of preserved cognition,"Ischemic small vessel disease (SVD) may lead to cognitive impairment, but cognitive deficits with a given burden of SVD vary significantly. The underlying mechanisms of impaired or preserved cognition are unknown. Here, we investigated the impact of ischemic SVD on rapid-onset cortical plasticity, as induced with a paired-associative stimulation protocol. To exclude concomitant effects of aging, we examined 12 middle-aged patients (48.3 +/- 8.3 years) with cerebral autosomal dominant arteriopathy with subcortical infarctions and leucoencephalopathy (CADASIL) who suffered from severe ischemic SVD and a group of 12 age-matched controls (49.9 +/- 8.3 years). Cognitive status, motor performance and learning, and motor cortex excitability in response to cathodal transcranial direct current stimulation (ctDCS) were assessed. White matter integrity was analyzed by conventional magnetic resonance imaging and diffusion tensor imaging. We found that cognitive and motor functions were largely preserved in CADASIL patients, while rapid-onset cortical plasticity was significantly higher in the CADASIL group compared with controls (repeated measures analysis of variance [group x time] interaction: P = 0.03). This finding was even more pronounced in patients with higher white matter lesion load. ctDCS revealed no evidence of cortical dysplasticity. We conclude that increased rapid-onset cortical plasticity may contribute to largely preserved cognitive and motor function despite extensive ischemic SVD.","Adult;Aged;CADASIL/ pathology/ physiopathology;Cognition/ physiology;Diffusion Magnetic Resonance Imaging;Evoked Potentials, Motor/physiology;Female;Humans;Male;Middle Aged;Neuronal Plasticity/ physiology;Neuropsychological Tests;Psychomotor Performance/physiology","List, J.;Duning, T.;Meinzer, M.;Kurten, J.;Schirmacher, A.;Deppe, M.;Evers, S.;Young, P.;Floel, A.",2011,Dec,10.1093/cercor/bhr071,0,
2881,Intravascular Lymphomatosis: Contribution of Cerebral MRI Findings to Diagnosis,"Intravascular lymphomatosis (IL) is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system (CNS). Most cases are not diagnosed until postmortem because of variable clinical presentation and nonspecific laboratory findings. Neuroimaging findings vary widely and range from diffuse involvement of the deep white matter to infarct-like lesions. Cerebral magnetic resonance imaging (MRI) may show parenchymal and meningeal gadolinium enhancement. The authors describe brain MRI findings of linear, punctate, and patchy enhancement suggestive of CNS",,"Liow, K.;Asmar, P.;Liow, M.;Spanaki, M.;Townsend, J. J.;Buys, S.;Baringer, J. R.;Osborn, A.",2000,2000,,0,
2882,Predictors and Clinical Impact of Incident Lacunes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy,"BACKGROUND AND PURPOSE: Previous studies in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy showed that accumulation of lacunes strongly relate to clinical severity. However, the potential predictors of incident lacunes and their clinical consequences over a short time frame have not been investigated. This study aimed to determine the predictors and clinical impact of such lesions in a large cohort of patients. METHODS: Two hundred and six NOTCH3 mutation carriers (mean age, 49.5+/-10.6 years) were followed up over 3 years. Incident lacunes were identified using difference imaging from 3-dimensional T1 images. Clinical events and change in different clinical scores such as the Mattis Dementia Rating Scale, Modified Rankin Scale, Barthel index, and time to complete part A and part B of Trail Making Test were recorded. Associations were analyzed with multivariable logistic regression analysis and ANCOVA. RESULTS: Over a mean period of 3.4+/-0.7 years, incident lacunes occurred in 51 of 206 patients. Both the number of lacunes (P<0.0001) and systolic blood pressure at baseline (P<0.01) were independent predictors of incident lacunes during follow-up. The results were still significant after excluding patients with systolic blood pressure >140 mm Hg. Incident lacunes were also associated with incident stroke and with change in time to complete Trail Making Test part B, initiation/perseveration subscale of the Mattis Dementia Rating Scale and Barthel Index over the study period. CONCLUSIONS: Systolic blood pressure and the number of prevalent lacunes are independent predictors of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. These lesions mainly impact executive performances and functional independence over 3 years.",Cadasil;cerebral small vessel disease;magnetic resonance imaging;risk factor;stroke,"Ling, Y.;De Guio, F.;Duering, M.;Jouvent, E.;Herve, D.;Godin, O.;Dichgans, M.;Chabriat, H.",2017,Feb,,0,
2883,Could iron accumulation be an etiology of the white matter change in Alzheimer's disease: using phase imaging to detect white matter iron deposition based on diffusion tensor imaging,"BACKGROUND/AIMS: To investigate if and where abnormal iron accumulation in white matter fibers occurs in patients with Alzheimer's disease (AD) by phase imaging and to relate these findings to white matter tract degeneration assessed by diffusion tensor imaging. METHODS: Twenty-five patients with AD and 20 normal controls underwent phase imaging and diffusion tensor imaging with a 3.0-tesla system. White matter fibers including fornix (Fx), genu of corpus callosum (GCC), splenium of corpus callosum (SCC), bilateral posterior cingulum (PC), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and frontal occipital fasciculus (IOF) were measured on a fractional anisotropy (FA) map, mean diffusivity (MD) map and phase map. RESULTS: Significantly decreased phase values and FA values in the Fx and PC regions were found in the AD group. The phase value in Fx had a moderately positive correlation with the FA value (r = 0.666, p = 0.000) in the AD group. Meanwhile, phase values in PC showed positive correlation with FA values (right side: r = 0.436, p = 0.033; left side: r = 0.458, p = 0.022, respectively). CONCLUSION: Iron accumulation of Fx and PC regions was significantly positively correlated with FA value, indicating that abnormal iron deposition may be one of the causes of white matter disruption in AD.","Aged;Alzheimer Disease/ etiology/metabolism/ pathology;Diffusion Tensor Imaging;Female;Humans;Iron/metabolism;Iron Overload/ complications/metabolism/ pathology;Leukoencephalopathies/ etiology/ pathology;Male;Middle Aged;Nerve Degeneration/etiology/metabolism/pathology;Nerve Fibers, Myelinated/metabolism/pathology","Ling, H. W.;Ding, B.;Wang, T.;Zhang, H.;Chen, K. M.",2011,,10.1159/000327167,0,
2884,"Cerebral lesions on magnetic resonance imaging, heart disease, and vascular risk factors in subjects without stroke. A population-based study","BACKGROUND AND PURPOSE: To assess the prevalence of asymptomatic abnormalities on magnetic resonance imaging of the brain and their possible relation to hypertension, heart disease, and carotid artery disease, we studied 77 randomly selected subjects (mean age, 65.1 years; range, 36 to 95 years) with no history of focal brain lesions. METHODS: The study protocol included magnetic resonance imaging of the brain, transthoracic and transesophageal echocardiography, ultrasonography of the carotid arteries, and electrocardiographic recording. Deep and periventricular white matter hyperintensities on magnetic resonance imaging were assessed both separately and together. RESULTS: On magnetic resonance imaging of the brain 62.3% (95% confidence interval [CI], 51.5% to 73.2%) of the subjects had white matter hyperintensities. These abnormalities increased significantly with age (chi 2 test; P = .0001), from 13.6% (95% CI, 0% to 28.0%) of subjects aged younger than 55 years to 85.2% (95% CI, 71.8% to 98.6%) of subjects aged 75 years or older. Six subjects had deep gray matter hyperintensities localized in the basal ganglia, and one had a cerebellar infarction. Stepwise logistic regression analysis identified age and a history of heart disease (but not echocardiographic findings) to be independently associated with deep and periventricular white matter hyperintensities. Hypertension was only independently associated with periventricular white matter hyperintensities. Of the 68 subjects examined with both transthoracic and transesophageal echocardiography, potential cardioembolic sources were detected in 38.2% (95% CI, 26.7% to 49.8%) of the subjects with transthoracic echocardiography and in 47.1% (95% CI, 35.2% to 58.9%) of those with transthoracic and transesophageal echocardiography combined. In subjects aged 75 years or older, a possible cardiac embolic source was detected in 64.0% on transthoracic echocardiography and in 72.0% on transthoracic and transesophageal echocardiography combined, compared with 5.3% and 15.8%, respectively, in subjects aged younger than 55 years. CONCLUSIONS: White matter hyperintensities and potential cardioembolic sources are frequently present in asymptomatic individuals, stressing the need for age-matched control subjects in studies of patients with stroke or dementia.","Adult;Aged;Brain Diseases/ diagnosis/epidemiology/ultrasonography;Carotid Stenosis/diagnosis/etiology;Cerebrovascular Disorders/diagnosis/epidemiology/etiology/ultrasonography;Echocardiography, Transesophageal;Embolism/complications/diagnosis;Female;Heart Diseases/complications/ diagnosis/epidemiology/ultrasonography;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors","Lindgren, A.;Roijer, A.;Rudling, O.;Norrving, B.;Larsson, E. M.;Eskilsson, J.;Wallin, L.;Olsson, B.;Johansson, B. B.",1994,May,,0,
2885,White matter signal abnormality quality differentiates mild cognitive impairment that converts to Alzheimer's disease from nonconverters,"The objective of this study was to assess how longitudinal change in the quantity and quality of white matter signal abnormalities (WMSAs) contributes to the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The Mahalanobis distance of WMSA from normal-appearing white matter using T1-, T2-, and proton density-weighted MRI was defined as a quality measure for WMSA. Cross-sectional analysis of WMSA volume in 104 cognitively healthy older adults, 116 individuals with MCI who converted to AD within 3years (mild cognitive impairment converter [MCI-C]), 115 individuals with MCI that did not convert in that time (mild cognitive impairment nonconverter [MCI-NC]), and 124 individuals with AD from the Alzheimer's Disease Neuroimaging Initiative revealed that WMSA volume was substantially greater in AD relative to the other groups but did not differ between MCI-NC and MCI-C. Longitudinally, MCI-C exhibited faster WMSA quality progression but not volume compared with matched MCI-NC beginning 18 months before MCI-C conversion to AD. The strongest difference in rate of change was seen in the time period starting 6months before MCI-C conversion to AD and ending 6months after conversion (p < 0.001). The relatively strong effect in this time period relative to AD conversion in the MCI-C was similar to the relative rate of change in hippocampal volume, a traditional imaging marker of AD pathology. These data demonstrate changes in white matter tissue properties that occur within WMSA in individuals with MCI that will subsequently obtain a clinical diagnosis of AD within 18months. Individuals with AD have substantially greater WMSA volume than all MCI suggesting that there is a progressive accumulation of WMSA with progressive disease severity, and that quality change predates changes in this total volume. Given the timing of the changes in WMSA tissue quality relative to the clinical diagnosis of AD, these findings suggest that WMSAs are a critical component for this conversion and are a critical component of this clinical syndrome.",,"Lindemer, E. R.;Salat, D. H.;Smith, E. E.;Nguyen, K.;Fischl, B.;Greve, D. N.",2015,1,,0,
2886,Regional staging of white matter signal abnormalities in aging and Alzheimer's disease,"White matter lesions, quantified as 'white matter signal abnormalities' (WMSA) on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic 'staging' of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC) aged 52-90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I-IV). A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were then additionally staged, and significant differences in the percent of each diagnostic group in Stages I and IV were observed, with more AD individuals residing in Stage IV and more OC and MCI individuals residing in Stage I. These data demonstrate a consistent regional scaling relationship between global and regional WMSA that can be used to classify individuals into one of four stages of white matter disease. White matter staging could play an important role in a better understanding and the treatment of cerebrovascular contributions to brain aging and dementia.",Aging;Alzheimer's disease;Cerebrovascular;Staging;White matter,"Lindemer, E. R.;Greve, D. N.;Fischl, B. R.;Augustinack, J. C.;Salat, D. H.",2017,,,0,
2887,Differential Regional Distribution of Juxtacortical White Matter Signal Abnormalities in Aging and Alzheimer's Disease,"BACKGROUND: White matter signal abnormalities (WMSA) (also known as 'hyperintensities') on MRI are commonly seen in normal aging and increases have been noted in Alzheimer's disease (AD), but whether there is a spatial specificity to these increases is unknown. OBJECTIVE: To discern whether or not there is a spatial pattern of WMSA in the brains of individuals with AD that differs from those who exhibit cognitively healthy aging. METHOD: Structural MRI data from the Alzheimer's Disease Neuroimaging Initiative public database were used to quantify WMSA in 35 regions of interest (ROIs). Regional measures were compared between cognitively healthy older controls (OC; n = 107) and individuals with a clinical diagnosis of AD (n = 127). Regional WMSA volume was also assessed in individuals with mild cognitive impairment (MCI; n = 74) who were 6, 12, and 24 months away from AD conversion. RESULTS: WMSA volume was significantly greater in AD compared to OC in 24 out of 35 ROIs after controlling for age, and nine were significantly higher after normalizing for total WMSA. Regions with greater WMSA volume in AD included rostral frontal, inferior temporal, and inferior parietal WM. In MCI, frontal and temporal regions demonstrated significantly greater WMSA volume with decreasing time-to-AD-conversion. DISCUSSION: Individuals with AD have greater regional volume of WMSA compared to OC regardless of age or total WMSA volume. Accumulation of regional WMSA is linked to time to AD conversion in individuals with MCI. These findings indicate WMSA is an important pathological component of AD development.",Aging;Alzheimer's disease;cerebrovascular;hyperintensities;magnetic resonance imaging;mild cognitive impairment;white matter,"Lindemer, E. R.;Greve, D. N.;Fischl, B.;Augustinack, J. C.;Salat, D. H.;Alzheimer's Disease Neuroimaging, Initiative",2017,,,0,
2888,Depressive symptoms and white matter changes in patients with dementia,"OBJECTIVE: The aim of the present study was to investigate if depressive symptoms in demented patients are associated with white matter changes (WMCs) in the brain. BACKGROUND: WMCs are frequently found in patients with dementia, as well as among elderly nondemented patients with depressive symptoms. However, it is less established whether or not WMCs are related to depressive symptoms in demented patients. METHODS: 67 (26 men, 41 women) patients with primary degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The patients were young-old (mean 68.1, SD 7.3). All patients underwent a standardized examination procedure and MRI of the brain. The degree of WMCs was visually rated, blindly. Depressive symptoms were rated according to the Gottfries-Brane-Steen scale (anxiety, fear-panic, depressed mood). RESULTS: No significant relationship was found between WMCs and depressive symptoms in the demented patients. CONCLUSION: The possible involvement of WMCs in the pathogenesis of depressive symptoms in dementia is unclear. A link between disruptions of frontal-subcortical pathways, due to WMCs, and depressive symptomatology in dementia has been hypothesised from earlier findings, which would imply common elements of pathogenesis for depressive symptomatology and cognitive impairment in dementia. However, the results of the present study do not add further support to this hypothesis.","Aged;Alzheimer Disease/complications/pathology;Brain/*pathology;Cohort Studies;Dementia/complications/*pathology;Dementia, Vascular/complications/pathology;Depressive Disorder/complications/*pathology;Female;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Male;Occipital Lobe/pathology;Parietal Lobe/pathology;Psychiatric Status Rating Scales;Temporal Lobe/pathology","Lind, K.;Jonsson, M.;Karlsson, I.;Sjogren, M.;Wallin, A.;Edman, A.",2006,Feb,10.1002/gps.1433,0,
2889,The MRI findings of sporadic Creutzfeldt-Jakob disease,"Objective: To study the MRI findings of sporadic Creutzfeldt-Jakob disease and its clinical relations. Methods: MRI of 10 cases CJD patients were examined 2-12 months after the onset. 6 cases were diagnosed using cerebral biopsy, 8 cases received CSF analysis for 14-3-3 protein, 8 cases showed special changes of electroencephalogram, PrP gene of 9 cases were analyzed. Results: Symmetric bilateral high signals were observed in caudate nucleus and Putamen in T (2)-weighted imaging and Flair imaging in 5 cases, but the pallidum and thalamus were normal. No changes were found in T1-weighted imaging. 2 cases showed brain atrophy, 1 case showed mild lacunar infarction, and the other 2 were normal. Conclusions: Abnormal signals in basal ganglia of 4 patients of 129Met/Met homozygote occurred after 2. 5 months averagely, they survived for 10.5 months at average. 1 patient of 129 Met/Val heterozygote showed abnormal signals in basal ganglia after 12 months, and survived for 16 months. The mean duration of patient with abnormal signals in basal ganglia (12.2 months) is longer than those without changes in basal ganglia (5.5 months). Symmetric high signal in bilateral caudate nucleus and Putamen is an important imaging feature of sCJD. It might be served as a diagnostic index in some circumstances.",,"Lin, S. H.;Zhao, J. X.;Jiang, X. M.;Song, X. N.",2004,23,,0,
2890,The occipital white matter lesions in Alzheimer's disease patients with visual hallucinations,"PURPOSE: Investigators have suggested that lesions responsible for visual hallucinations (VHs) are situated in the visual association cortex. The aim of this study was to assess the relationship between occipital white matter lesions and VHs in Alzheimer's disease (AD) patients. METHODS: AD patients with a history of VHs (AD+VH) and those without (AD-VH) were retrospectively studied. The two groups of patients were matched by sex and mental state. All subjects underwent brain magnetic resonance image (MRI) scans. The periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWHs) on MRIs were rated by two raters using a semiquantitative scoring method (0=absent; 6=confluent). RESULTS: Five AD+VH patients and five AD-VH patients were enrolled into this study. The occipital PVH score was higher in the AD+VH patients than in the AD-VH patients. The occipital DWH score was zero in both groups. CONCLUSION: The presence of VHs in AD was associated with increased occipital PVHs and an absence of occipital DWHs on brain MRIs, implying that structural lesions in the geniculocalcarine region and preserved subcortical connections with visual association areas are involved in the genesis of VHs in AD.","Aged;Alzheimer Disease/ complications/ pathology;Female;Hallucinations/ complications/ pathology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Occipital Lobe/ pathology;Visual Cortex/ pathology","Lin, S. H.;Yu, C. Y.;Pai, M. C.",2006,Nov-Dec,10.1016/j.clinimag.2006.09.025,0,
2891,Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease,"Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC). Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 +/- 8.2 year old), 41 aMCI patients (aged 68.2 +/- 6.4 year old) and 40 NC subjects (aged 65.7 +/- 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively. Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients. Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients.",Alzheimer disease;cerebral cortex;diffusion MRI;mild cognitive impairment;parcellation,"Lin, S. H.;Hsu, W. C.;Ng, S. H.;Cheng, J. S.;Khegai, O.;Huang, C. C.;Chen, Y. L.;Chen, Y. C.;Wang, J. J.",2016,,,0,
2892,Cranial computed tomography in ischemic stroke patients with and without dementia--a prospective study,"Stroke patients were assessed by brain CT scan, accompanied by demographic and clinical factors to predict the development of dementia following an ischemic episode. Vascular dementia was defined by NINDS-AIREN criteria. From 50 demented and 50 non-demented stroke patients, we analyzed the location of lesion, counted the numbers of lacunae, and semiquantitatively assessed the size of infarction, severity of overall white matter lesions (WML), and degree of brain atrophy. Compared to the non-demented patients, the demented patients: 1) encountered more stroke episodes (p < 0.001); 2) had more lacunae at bilateral basal ganglion (p < 0.001) or thalamus (p < 0.01); and 3) tended to have lesions in left cortex (p < 0.001), particularly a large infarct at the parietal (p < 0.001) or temporal lobe (p < 0.001). Periventricular changes (p < 0.001), subcortical WML (p < 0.001), overall WML (p < 0.001), and brain atrophy (p < 0.05) were also more severe in the demented group. However, no difference existed in demographic factors between the two groups. We concluded that several factors were important in developing dementia following an ischemic stroke, and the order by logistic regression would be: the severity of overall WML, left parietal infarct, and numbers of thalamic lacunae.","Aged;Brain/*radiography;Brain Ischemia/*radiography;Dementia, Vascular/*radiography;Female;Humans;Male;Middle Aged;Prospective Studies;*Tomography, X-Ray Computed","Lin, R. T.;Lai, C. L.;Tai, C. T.;Liu, C. K.;Howng, S. L.",1998,Apr,,0,
2893,Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology,"Leukoaraiosis (LA), also called white matter lesions (WMLs) and white matter hyperintensities (WMHs), is a frequent neuroimaging finding commonly seen on magnetic resonance imaging brain scans of elderly people with prevalence ranging from 50% to 100%. Although it remains asymptomatic, LA is not considered to be benign, and it is showed to be related to a host of poor clinical outcomes and increases the risk of disability, dementia, depression, stroke, and the overall morbidity and mortality. Pathologically",,"Lin, Q.;Huang, W. Q.;Tzeng, C. M.",2015,1,,0,
2894,Incidence and risk factors of leukoaraiosis from 4683 hospitalized patients: A cross-sectional study,"Leukoaraiosis (LA) refers to white matter hyperintensities or white matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of the brain; this disease is associated with an increased risk of stroke, dementia, and cognitive decline. The aims of the study are to assess the incidence of LA and its associated risk factors in a Chinese population.A hospital-based cross-sectional study was conducted that included 4683 patients who were 40 years or older. Data collected included age, sex, hypertension, diabetes, smoking, drinking, homocysteine (HCY), and low-density lipoprotein cholesterol (LDL-C) levels in the blood in addition to brain MRI information. We examined the relationship of those putative risk factors with LA, LA occurrence, and LA progression through single-factor and multivariate analyses.Of the total subjects, 58.3% (2731/4683 cases) suffered from LA. LA was more frequent amongst elderly females, particularly in those older than 60, compared to men. The incidence of LA increased with age. Age, sex, hypertension, diabetes, smoking, and HCY levels all were risk factors for LA. Amongst those risk factors, both smoking and high HCY levels were associated with the onset process of LA. Moreover, the multivariate logistic analysis revealed that both drinking and abnormal LDL-C levels were positive regulators in the progression process of LA.This study revealed that the incidence of LA is high in hospitalized patients in China; moreover, age, sex, hypertension, diabetes mellitus, smoking, drinking, and abnormal HCY and LDL-C levels were found to be associated with overall LA risk, LA onset, or LA progression. These results provide insight into strategies for the prevention and treatment of LA.","Adult;Aged;Aged, 80 and over;China/epidemiology;Cross-Sectional Studies;Disease Progression;Female;Hospitalization/statistics & numerical data;Humans;Incidence;Leukoaraiosis/ epidemiology;Male;Middle Aged;Retrospective Studies;Risk Factors;Sex Distribution","Lin, Q.;Huang, W. Q.;Ma, Q. L.;Lu, C. X.;Tong, S. J.;Ye, J. H.;Lin, H. N.;Gu, L.;Yi, K. H.;Cai, L. L.;Tzeng, C. M.",2017,Sep,,0,
2895,Microstructural White Matter Abnormalities and Cognitive Dysfunction in Subcortical Ischemic Vascular Disease: an Atlas-Based Diffusion Tensor Analysis Study,"Recent studies in subcortical ischemic vascular disease (SIVD) suggest the involvement of white matter (WM) abnormalities underlying the pathogenesis of cognitive function impairment. Here, we performed magnetic resonance diffusion tensor imaging (DTI) on detecting WM damage and to investigate the correlations between DTI measures and cognitive dysfunction in SIVD patients. Fifty right-handed SIVD patients were recruited and divided into vascular cognitive impairment on dementia (VCIND) group and normal cognition (NC) group. Twenty-two VCIND patients and 28 NC patients underwent DTI scanning and neuropsychological assessment. Atlas-based analysis (ABA) was performed on each subject for extracting FA and MD measures from supratentorial tracts. Among VCIND, as compared to NC patients, decreased FA and increased MD were observed in all projection fibers (bilateral anterior, posterior limb, and retrolenticular part of internal capsule, anterior, superior, and posterior corona radiata and posterior thalamic radiation), association fibers (bilateral sagittal stratum, external capsule, cingulum, fornix, and stria terminalis, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and uncinate fasciculus), and commissural fibers (genu, body, splenium, and bilateral tapetum of corpus callosum). Furthermore, we also found that MoCA scores correlated with DTI values in all supratentorial WM tracts. The results suggested that SIVD patients demonstrated abnormal WM connectivity in all supratentorial regions. Moreover, the severity of damage in WM tracts correlated with cognitive dysfunction.","Aged;Aged, 80 and over;Brain Ischemia/ pathology/physiopathology;Case-Control Studies;Cognition;Dementia, Vascular/ pathology/physiopathology;Diffusion Tensor Imaging;Female;Humans;Male;White Matter/ pathology","Lin, L.;Xue, Y.;Duan, Q.;Sun, B.;Lin, H.;Chen, X.;Luo, L.;Wei, X.;Zhang, Z.",2015,Jun,10.1007/s12031-015-0550-5,0,
2896,Intervention versus aggressive medical therapy for cognition in severe asymptomatic carotid stenosis,"BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of =70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization. MATERIALS AND METHODS: Patients with asymptomatic, unilateral, <70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment. RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P=.045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network. CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in<70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.",carotid artery stent;self expanding stent;antithrombocytic agent;aged;article;asymptomatic disease;carotid artery obstruction;carotid artery stenting;cerebral revascularization;cognition;controlled clinical trial;controlled study;corpus callosum;default mode network;diffusion tensor imaging;disease severity;dizziness;dorsal attention network;dual antiplatelet therapy;female;follow up;fractional anisotropy;functional connectivity;functional magnetic resonance imaging;functional neuroimaging;human;insula;male;medial prefrontal cortex;neuropsychological test;recall;short term memory;verbal memory;white matter;Precise;Wallstent,"Lin, C. J.;Chang, F. C.;Chou, K. H.;Tu, P. C.;Lee, Y. H.;Lin, C. P.;Wang, P. N.;Lee, I. H.",2016,,10.3174/ajnr.A4798,0,
2897,Prediction of vascular risk after stroke - protocol and pilot data of the prospective Cohort with incident stroke (PROSCIS),"Rationale: Long-term risk of vascular disease is substantially increased after stroke with several models proposed to predict subsequent stroke and other vascular events after an index event. However, recent validation studies demonstrate limited predictive properties of available prognostic models. Aims: We aim to determine prediction models of different complexity for the combined vascular end-point of stroke, myocardial infarction, and vascular death at three-years after first-ever stroke. An independent external validation of the developed models will be performed. Design: Prospective observational hospital-based cohort study of patients after first-ever stroke. Methods: The new predictive models will be developed using the following steps: (1) Development of a basic score based on clinical history data (e.g. hypertension, myocardial infarction, and atrial fibrillation); (2) Development of an advanced score including additional factors such as blood-based biomarkers and results of vascular imaging; (3) Comparing the models fit using different methods (discrimination, calibration); (4) Assessment of clinical utility of an advanced score using methods based on reclassification tables (e.g. net reclassification improvement, integrated discrimination improvement, decision curve analysis); and (5) Investigation of external validity. Outcomes: Primary outcome is a combined vascular end-point composed of stroke, myocardial infarction, and vascular death at three-years after stroke. Furthermore, each component of the composite end-point will be investigated individually and the patterns and time points of risk transitions between vascular end-points and stroke sub-types will be determined. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.",,"Liman, T. G.;Zietemann, V.;Wiedmann, S.;Jungehuelsing, G. J.;Endres, M.;Wollenweber, F. A.;Wellwood, I.;Dichgans, M.;Heuschmann, P. U.",2013,August,,0,
2898,Endovascular Therapy for Large Vessel Stroke in the Elderly: Hope in the New Stroke Era,"Background and Purpose: Acute ischemic stroke (AIS) in the elderly encompasses approximately one-third of all AIS cases. Outcome data have been for the most part discouraging in this population. We aim to evaluate the outcomes in a large contemporary series of elderly patients treated with thrombectomy. Methods: Retrospective analysis of a single-center endovascular database for consecutive elderly (≥80 years) patients treated for anterior circulation large vessel occlusion AIS between September 2010 and April 2015. Univariate- and multivariate analyses were performed to identify the predictors of good clinical outcome (90-day modified Ranking Scale [mRS] ≤2). Receiver operating characteristic curves were used to calculate the optimal final infarct volume (FIV) threshold to predict good outcomes. Results: A total of 111 patients met our inclusion criteria (mean age 84.8 ± 4.2 years; National Institutes of Health Stroke Scale [NIHSS] score 19.1 ± 5.6; time from last-known normal to puncture, 349.6 ± 246.6 min; 33% male; 68% Alberta Stroke Program Early CT Score [ASPECTS] ≥8). The rates of successful reperfusion (modified treatment in cerebral ischemia ≥2b), symptomatic intracranial hemorrhage and 90-day mortality were 80%, 7% and 41%, respectively. The overall rate of good outcome was 29% (n = 32/111) but was 52% (n = 13/25) in patients with baseline mRS score of 0-2 who were selected based on CT perfusion and treated with stent retrievers. On multivariate analysis, only ASPECTS (OR 2.17; 95% CI 1.28-3.67.7; p = 0.004) and baseline NIHSS score (OR 0.87; 95% CI 0.77-0.97; p = 0.013) were independently associated with good outcome. A FIV ≤16 ml demonstrated the greatest accuracy for identifying good outcomes (sensitivity 75.0%, specificity 82.6%). Conclusions: Our results are encouraging demonstrating nearly one-third of elderly patients achieving full independence at 90 days. Contemporary treatment paradigms employing optimized patient selection and modern thrombectomy technology may result in even better outcomes.",aged;article;atrial fibrillation;blood vessel occlusion;brain hemorrhage;brain ischemia;controlled study;diabetes mellitus;diagnostic test accuracy study;dyslipidemia;endovascular surgery;female;human;hypertension;major clinical study;male;mental deterioration;National Institutes of Health Stroke Scale;predictive value;priority journal;reperfusion injury;retrospective study;sensitivity and specificity;thrombectomy;treatment outcome,"Lima, A.;Haussen, D. C.;Rebello, L. C.;Dehkharghani, S.;Grossberg, J.;Grigoryan, M.;Frankel, M.;Nogueira, R. G.",2016,,10.1159/000446852,0,
2899,R54C mutation of NOTCH3 gene in the first rungus family with CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan-Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n=9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study.",genomic DNA;Notch3 receptor;adult;article;CADASIL;cerebrovascular accident;clinical article;clinical feature;disease severity;ethnic group;exon;family;family history;female;genetic analysis;genetic association;human;image analysis;indigenous people;Malaysia;male;middle aged;migraine;missense mutation;molecular pathology;NOTCH3 gene;nuclear magnetic resonance imaging;penetrance;phenotypic variation;Rungus;sibling;white matter lesion,"Lim, K. S.;Tan, A. H.;Lim, C. S.;Chua, K. H.;Lee, P. C.;Ramli, N.;Rajahram, G. S.;Hussin, F. T.;Wong, K. T.;Bhattacharjee, M. B.;Ng, C. C.",2015,,,0,
2900,Differential white matter connectivity in early mild cognitive impairment according to CSF biomarkers,"Mild cognitive impairment (MCI) is a heterogeneous group and certain MCI subsets eventually convert to dementia. Cerebrospinal fluid (CSF) biomarkers are known to predict this conversion. We sought evidence for the differences in white matter connectivity between early amnestic MCI (EMCI) subgroups according to a CSF phosphorylated tau181p/amyloid beta1-42 ratio of 0.10. From the Alzheimer's Disease Neuroimaging Initiative database, 16 high-ratio, 25 low-ratio EMCI patients, and 20 normal controls with diffusion tensor images and CSF profiles were included. Compared to the high-ratio group, radial diffusivity significantly increased in both sides of the corpus callosum and the superior and inferior longitudinal fasciculus in the low-ratio group. In widespread white matter skeleton regions, the low-ratio group showed significantly increased mean, axial, and radial diffusivity compared to normal controls. However, the high-ratio group showed no differences when compared to the normal group. In conclusion, our study revealed that there were significant differences in white matter connectivity between EMCI subgroups according to CSF phosphorylated tau181p/amyloid beta1-42 ratios.",Aged;Aniline Compounds/pharmacology/therapeutic use;Biomarkers/cerebrospinal fluid;Case-Control Studies;Ethylene Glycols/pharmacology/therapeutic use;Female;Humans;Male;Mild Cognitive Impairment/ cerebrospinal fluid/drug therapy/ physiopathology;Nerve Net/pathology/ physiopathology;White Matter/drug effects/pathology/ physiopathology;tau Proteins/cerebrospinal fluid,"Lim, J. S.;Park, Y. H.;Jang, J. W.;Park, S. Y.;Kim, S.",2014,,10.1371/journal.pone.0091400,0,
2901,Grey and White Matter Changes across the Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Continuum,"There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum. © 2012 Lillo et al.",,"Lillo, P.;Mioshi, E.;Burrell, J. R.;Kiernan, M. C.;Hodges, J. R.;Hornberger, M.",2012,,,0,
2902,Visualization and Quantification of Three-Dimensional Stereotactic Surface Projections for 18F-Flutemetamol PET using variable depth,"Three-dimensional stereotactic surface projection (3D-SSP) is a widely used method for analysis of clinical 18F-FDG brain studies. However, for PET amyloid scans the use of 3D-SSP is challenging due to non-specific uptake in white matter. Our objective was to implement a method for 3D-SSP quantification and visualization of 18F-flutemetamol images that avoids extraction of white matter signal. METHODS: Triangulated brain surface models were extracted from a T1 weighted MR template image. Using an 18F-flutemetamol negative template, a maximum depth for each vertex on the surface models was calculated to avoid extraction of white matter. The method was evaluated using 18F-flutemetamol images from two cohorts; cohort 1 consisted of 105 healthy volunteers and was used to create a normal database for each reference region. Cohort 2 consisted of 171 subjects including patients with Alzheimer's disease, mild cognitive impairment and healthy volunteers. Images were spatially normalized using an adaptive template registration method and SUVR 3D-SSP values were computed, using pons and cerebellar cortex as reference regions. Images from cohort 2 were then compared to the normal database and classified into negatives and positives, based on a calculated Z-score threshold. The results were compared to consensus visual read results from five trained readers blinded to clinical data. RESULTS: With pons as reference region the optimal Z-score threshold was 1.97, resulting in an overall agreement with visual read results in 170 out of 171 images (99.42%). Using cerebellum cortex as reference region, the optimal Z-score threshold was 2.41 with an overall agreement with visual read in 168 out of 171 images (98.25%). CONCLUSION: Variable depth 3D-SSP allows computation and visualisation of 18F-flutemetamol 3D-SSP maps with minimized contribution from white matter signal while retaining sensitivity in detecting grey matter signal.",,"Lilja, J. A.;Thurfjell, L.;Sorensen, J.",2016,Feb 16,10.2967/jnumed.115.169169,0,
2903,Visualization and Quantification of 3-Dimensional Stereotactic Surface Projections for 18F-Flutemetamol PET Using Variable Depth,"Three-dimensional stereotactic surface projection (3D-SSP) is a widely used method for the analysis of clinical (18)F-FDG brain studies. However, for PET amyloid scans the use of 3D-SSP is challenging because of nonspecific uptake in white matter. Our objective was to implement a method for 3D-SSP quantification and visualization of (18)F-flutemetamol images that avoids extraction of white matter signal. METHODS: Triangulated brain surface models were extracted from a T1-weighted MR template image. Using an (18)F-flutemetamol-negative template, a maximum depth for each vertex on the surface models was calculated to avoid extraction of white matter. The method was evaluated using (18)F-flutemetamol images from 2 cohorts. Cohort 1 consisted of 105 healthy volunteers and was used to create a normal database for each reference region. Cohort 2 consisted of 171 subjects including patients with Alzheimer disease and mild cognitive impairment and healthy volunteers. Images were spatially normalized using an adaptive template registration method, and SUV ratio 3D-SSP values were computed using the pons and cerebellar cortex as reference regions. Images from cohort 2 were then compared with the normal database and classified into negatives and positives, based on a calculated z score threshold. The results were compared with consensus visual interpretation results from 5 trained interpreters blinded to clinical data. RESULTS: With the pons as the reference region, the optimal z score threshold was 1.97, resulting in an overall agreement with visual interpretation results in 170 of 171 images (99.42%). With the cerebellar cortex as the reference region, the optimal z score threshold was 2.41, with an overall agreement with visual interpretation in 168 of 171 images (98.25%). CONCLUSION: Variable-depth 3D-SSP allows computation and visualization of (18)F-flutemetamol 3D-SSP maps, with minimized contribution from white matter signal while retaining sensitivity in detecting gray matter signal.",Alzheimer's disease;amyloid;brain mapping;flutemetamol;positron emission tomography;stereotactic surface projections,"Lilja, J.;Thurfjell, L.;Sorensen, J.",2016,Jul,10.2967/jnumed.115.169169,0,
2904,Arterial stiffness and medial temporal lobe atrophy in elders with memory disorders,"OBJECTIVES: Hypertension is a risk factor for cognitive impairment and dementia. Arterial stiffness could be involved in the mechanisms of vascular cognitive impairment and in Alzheimer's disease. We examined the association between arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), and medial temporal lobe (MTL) atrophy, a biomarker of Alzheimer's disease. METHODS: Elderly community-dwelling study participants (n = 149) with memory complaints were diagnosed with Alzheimer's disease (n = 62) or mild cognitive impairment (n = 87) at a memory clinic. PWV, peripheral and central blood pressure (SBP), and pulse pressure (PP) were measured. MTL was graded on MRI according to the Scheltens' scale. RESULTS: Mean age was 79.5 (SD = 5) years old, 36% of study participants were men. MTL was absent or discrete in 23.5%, moderate in 53.0% and severe in 23.5% of study participants. PWV was 9.3 (2.2) m/s in none or discrete, 11.1 (2.8) in moderate and 13.5 (4.0) in severe MTL atrophy (P < 0.0001). PWV, central SBP, and central PP were overall associated with MTL atrophy after adjustment for age, sex, antihypertensive treatments and white matter lesions, and further adjusted for mean BP for PWV, whereas peripheral SBP and PP were not associated with MTL atrophy. PWV was significantly associated with severe MTL atrophy [odds ratio = 3.69 (95% confidence interval = 1.69-8.05), P = 0.001] and marginally associated with moderate MTL atrophy [1.80 (0.92-3.53), P = 0.09]. Furthermore PWV was significantly associated with severe MTL atrophy in Alzheimer's disease and mild cognitive impairment study participants separately. CONCLUSION: The result of this study suggests a role of arterial stiffness in the pathogenesis of Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/pathology/ physiopathology;Atrophy/diagnostic imaging;Blood Pressure;Cognitive Dysfunction/ physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Odds Ratio;Pulse Wave Analysis;Risk Factors;Temporal Lobe/diagnostic imaging/ pathology;Vascular Stiffness","Lilamand, M.;Vidal, J. S.;Plichart, M.;De Jong, L. W.;Duron, E.;Hanon, O.",2016,Jul,,0,2905
2905,Arterial stiffness and medial temporal lobe atrophy in elders with memory disorders,"OBJECTIVES: Hypertension is a risk factor for cognitive impairment and dementia. Arterial stiffness could be involved in the mechanisms of vascular cognitive impairment and in Alzheimer's disease. We examined the association between arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV), and medial temporal lobe (MTL) atrophy, a biomarker of Alzheimer's disease. METHODS: Elderly community-dwelling study participants (n = 149) with memory complaints were diagnosed with Alzheimer's disease (n = 62) or mild cognitive impairment (n = 87) at a memory clinic. PWV, peripheral and central blood pressure (SBP), and pulse pressure (PP) were measured. MTL was graded on MRI according to the Scheltens' scale. RESULTS: Mean age was 79.5 (SD = 5) years old, 36% of study participants were men. MTL was absent or discrete in 23.5%, moderate in 53.0% and severe in 23.5% of study participants. PWV was 9.3 (2.2) m/s in none or discrete, 11.1 (2.8) in moderate and 13.5 (4.0) in severe MTL atrophy (P < 0.0001). PWV, central SBP, and central PP were overall associated with MTL atrophy after adjustment for age, sex, antihypertensive treatments and white matter lesions, and further adjusted for mean BP for PWV, whereas peripheral SBP and PP were not associated with MTL atrophy. PWV was significantly associated with severe MTL atrophy [odds ratio = 3.69 (95% confidence interval = 1.69-8.05), P = 0.001] and marginally associated with moderate MTL atrophy [1.80 (0.92-3.53), P = 0.09]. Furthermore PWV was significantly associated with severe MTL atrophy in Alzheimer's disease and mild cognitive impairment study participants separately. CONCLUSION: The result of this study suggests a role of arterial stiffness in the pathogenesis of Alzheimer's disease.",,"Lilamand, M.;Vidal, J. S.;Plichart, M.;De Jong, L. W.;Duron, E.;Hanon, O.",2016,Apr 28,10.1097/hjh.0000000000000954,0,
2906,"Longitudinal changes of fractional anisotropy in Alzheimer's disease patients treated with galantamine: a 12-month randomized, placebo-controlled, double-blinded study","Diffusion tensor imaging (DTI) demonstrates decline of fractional anisotropy (FA) as a marker of fiber tract integrity in Alzheimer's disease (AD). We aimed to assess the longitudinal course of white matter microstructural changes in AD and healthy elderly control (HC) subjects and to evaluate the effects of treatment with the cholinesterase inhibitor galantamine on white matter microstructure in AD patients. We enrolled 28 AD patients and 11 healthy elderly control subjects (HC). AD patients were randomly assigned to 6-month double-blind galantamine treatment or placebo, with a 6-month open-label extension phase. DTI was performed at baseline, as well as at 6 and 12-month follow-up in AD patients. The HC subjects underwent DTI at baseline and 12-month follow-up without treatment. We measured FA in regions of interest covering the posterior cingulate and corpus callosum. At 6-month follow-up, the AD group showed significant FA decline in the left posterior cingulate. FA decline was significantly preserved in the posterior body of the corpus callosum in AD group with treatment compared to placebo. At 12-month follow-up, the AD patients showed no differences in FA decline between initial treatment and placebo groups after the 6-month open-label extension phase. A significant FA decline occurred in the left posterior cingulate across the AD and HC groups without between-group differences. DTI demonstrated FA decline in intracortically projecting fiber tracts in aging and AD over 1 year. Galantamine had limited impact on regional FA decline, which was not preserved after additional 6-month open-label treatment.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/drug therapy/physiopathology;Anisotropy;Biological Availability;Cholinesterase Inhibitors/administration & dosage/pharmacokinetics;Corpus Callosum/drug effects/pathology/physiopathology;Diffusion Tensor Imaging/ methods;Double-Blind Method;Female;Galantamine/pharmacokinetics;Gyrus Cinguli/drug effects/pathology/physiopathology;Humans;Male;Nerve Fibers, Myelinated/drug effects/pathology;Neuropsychological Tests;Outcome Assessment (Health Care)/methods","Likitjaroen, Y.;Meindl, T.;Friese, U.;Wagner, M.;Buerger, K.;Hampel, H.;Teipel, S. J.",2012,Jun,10.1007/s00406-011-0234-2,0,
2907,Environmental reduplication in a patient with right middle cerebral artery occlusion,"Environmental reduplication or reduplicative paramnesia is one of the content-specific delusions (CSD) which is characterized by reduplication of places. CSD has been reported in focal and diffuse cerebral disorders. A focal lesion such as frontal lobes and the right hemispheric lesion have been documented. The authors describe a 66 year-old woman who had a delusion of misidentification for place one month after right middle cerebral artery occlusion. The patient did not have any history of schizophrenia or other psychiatric diseases. The patient believed that her car, furniture and house were duplicated. She also mentioned that her son and friends tried to takeover all of her properties and told everyone that she was insane. The prominent cortical signs were tactile and visual neglect. Neuropsychological assessments revealed poor attention but she had neither confusion nor dementia. Clock drawing and construction tests revealed visuospatial impairment which was compatible with non-dominant hemispheric abnormality. MRI showed evidence of cerebral infarction in the right middle cerebral artery territory. Only one similar patient who had an intracerbral hematoma of the right frontal lobe has been reported in the literature. The role of occipitoparietal and fronto-temporal lobes or their connections in environmental reduplication is proposed.",aged;article;brain hematoma;brain infarction;case report;confusion;content specific delusion;delusion;environmental reduplication;female;frontal lobe;human;mental disease;middle cerebral artery occlusion;neuropsychology;nuclear magnetic resonance imaging;paramnesia;schizophrenia;tactile discrimination;visual deprivation,"Likitcharoen, Y.;Phanthumchinda, K.",2004,,,0,
2908,Lenticulostriate arterial lumina are normal in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a high-field in vivo MRI study,"BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease. Although postmortem studies have demonstrated mural thickening in leptomeningeal arteries and lenticulostriate perforating arteries, it is unclear whether this also leads to luminal narrowing. High-field MRI scanners enable in vivo imaging of the lumen of the lenticulostriate arteries. The aim of this study is to examine the luminal diameters of lenticulostriate arteries in living patients with CADASIL and to investigate whether luminal narrowing is correlated with the number of lacunar infarcts in the basal ganglia. METHODS: Twenty-two NOTCH3 mutation carriers and 11 healthy control subjects were examined using high-resolution 3-dimensional time-of-flight MR angiography imaging on a 7-T MRI scanner. Scans were analyzed for the presence of focal stenotic segments. The total number, length, and total cross-sectional area of lenticulostriate arteries were measured and compared between mutation carriers and control subjects. These measurements were correlated with age, disease duration, and number of lacunar infarcts in the basal ganglia. RESULTS: No stenotic segments were observed. No differences between mutation carriers and control subjects were found in total number of end branches (mutation carriers: mean, 14.6; control subjects: mean, 12.8), length of the lenticulostriate system, or total cross-sectional area of lenticulostriate artery lumina. Measurements of lenticulostriate artery lumina were not associated with lacunar infarct load in the basal ganglia area or with basal ganglia hyperintensities. CONCLUSIONS: Three-dimensional time-of-flight MR angiographic on 7 T showed no differences in luminal diameters of lenticulostriate arteries between patients with CADASIL and control subjects.","Adult;Age Factors;Aged;Anatomy, Cross-Sectional;Basal Ganglia/pathology;Basal Ganglia Cerebrovascular Disease/ pathology;CADASIL/epidemiology/ pathology;Cerebral Arteries/pathology;Constriction, Pathologic;Female;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Receptors, Notch/genetics","Liem, M. K.;van der Grond, J.;Versluis, M. J.;Haan, J.;Webb, A. G.;Ferrari, M. D.;van Buchem, M. A.;Lesnik Oberstein, S. A.",2010,Dec,10.1161/strokeaha.110.586883,0,
2909,Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke and cognitive decline. Previous studies have shown an association between white matter hyperintensities on brain MRI and cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. In the general population the presence of lacunar infarcts and microbleeds is also associated with cognitive dysfunction. The objective of this study was to determine to what extent lacunar infarcts and microbleeds on MRI contribute to cognitive decline in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. METHODS: NOTCH3 mutation analysis was performed in 62 symptomatic and asymptomatic members of 15 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy families. Neuropsychological tests were performed on the same day as the MRI examination. MRI was semi-quantitatively scored for white matter hyperintensities, infarct lesion load, and microbleeds. Regression analysis was performed to test the association between MRI abnormalities and neuropsychological test results. RESULTS: Forty individuals had a NOTCH3 mutation and 22 did not. Severity of cognitive dysfunction in mutation carriers was independently associated with MRI infarct lesion load (P<0.05). In contrast, WMH lesion load and microbleeds were not associated with cognitive dysfunction after correcting for age. CONCLUSIONS: Lacunar infarct lesion load is the most important MRI parameter associated with cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.","Adult;Brain Infarction/complications/*pathology/psychology;CADASIL/complications/*pathology/psychology;Cognition Disorders/etiology/*pathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Receptors, Notch/genetics","Liem, M. K.;van der Grond, J.;Haan, J.;van den Boom, R.;Ferrari, M. D.;Knaap, Y. M.;Breuning, M. H.;van Buchem, M. A.;Middelkoop, H. A.;Lesnik Oberstein, S. A.",2007,Mar,10.1161/01.STR.0000257968.24015.bf,0,
2910,7 T MRI reveals diffuse iron deposition in putamen and caudate nucleus in CADASIL,"OBJECTIVE: Diffuse iron deposition in the brain is commonly found in older people. One of the possible mechanisms that contribute to this iron deposition is cerebral small vessel disease. The aim of this study is to quantify diffuse iron deposition in patients with the hereditary small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: 25 NOTCH3 mutation carriers and 18 healthy controls were examined using high-resolution T2*-weighted imaging on a 7 T whole body MRI scanner. Susceptibility-weighted MRI scans were analysed for areas of signal loss and increased phase shift. Phase shift measurements in deep grey nuclei, cortex and subcortical white matter were compared between mutation carriers and controls. For confirmation, ex vivo brain specimens from another three patients with CADASIL were analysed for iron deposition using ex vivo MRI combined with iron histochemistry. RESULTS: In vivo MRI showed areas of decreased signal intensity and increased phase shift in mutation carriers. Compared with healthy controls, mutation carriers had significantly higher phase shift in the putamen (p=0.0002) and caudate nucleus (p=0.006). Ex vivo MRI showed decreased signal intensity in the putamen and caudate nucleus in all specimens. Histochemistry confirmed the presence of iron deposition in these nuclei. CONCLUSIONS: This study demonstrates increased diffuse iron accumulation in the putamen and caudate nucleus in patients with the small vessel disease CADASIL. This supports the hypothesis that small vessel disease contributes to the process of increased iron accumulation in the general population.","Adult;Autopsy;CADASIL/ metabolism/pathology;Caudate Nucleus/ metabolism/pathology;Cerebral Hemorrhage/pathology;Echo-Planar Imaging;Female;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Iron/ metabolism;Iron Metabolism Disorders/ metabolism;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Putamen/ metabolism/pathology;Receptors, Notch/genetics;Whole Body Imaging","Liem, M. K.;Lesnik Oberstein, S. A.;Versluis, M. J.;Maat-Schieman, M. L.;Haan, J.;Webb, A. G.;Ferrari, M. D.;van Buchem, M. A.;van der Grond, J.",2012,Dec,10.1136/jnnp-2012-302545,0,
2911,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: progression of MR abnormalities in prospective 7-year follow-up study,"PURPOSE: To prospectively investigate the patterns and rates of progression of magnetic resonance (MR) imaging abnormalities in a well-documented cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) cohort 7 years after baseline and to identify the prognostic factors that determine the rates and patterns of this progression. MATERIALS AND METHODS: The local ethics committee approved the study, and informed consent was obtained from all participants. From 12 unrelated families, 25 patients who were NOTCH3 mutation carriers and 13 who were non-mutation carriers were examined clinically and with standardized MR imaging at baseline and after 7 years. The progression of white matter hyperintensities (WMHs), lacunar infarcts, microbleeding, and brain volume loss was measured semiquantitatively. Correlation testing and group comparison testing were performed to identify the risk factors associated with increased progression of CADASIL-related MR abnormalities. RESULTS: Compared with the non-mutation carriers, the mutation carriers showed significant increases in numbers of lacunar infarct (P < .01), WMH (P < .01), and microbleed (P < .05) lesions but no increased loss of brain volume. The distributions of new WMHs and new lacunar infarcts at follow-up were similar to the distributions of these abnormalities at baseline. High WMH (P < .05), lacunar infarct (P < .01), and microbleed (P < .01) lesion loads at baseline--but not cardiovascular risk factors--were associated with faster progression of these abnormalities. CONCLUSION: Patients with CADASIL who have a high MR abnormality lesion load at baseline are at risk for faster progression of MR abnormalities.","Adult;Brain/pathology;Brain Infarction/pathology;CADASIL/genetics/ pathology/physiopathology;Cerebral Hemorrhage/pathology;Disease Progression;Female;Follow-Up Studies;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Organ Size;Prospective Studies;Receptors, Notch/genetics","Liem, M. K.;Lesnik Oberstein, S. A.;Haan, J.;van der Neut, I. L.;van den Boom, R.;Ferrari, M. D.;van Buchem, M. A.;van der Grond, J.",2008,Dec,10.1148/radiol.2492080357,0,
2912,MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study,"BACKGROUND: Cognitive decline is one of the clinical hallmarks of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebrovascular disease caused by NOTCH3 mutations. In this 7-year follow-up study, we aimed to determine whether there are associations between the different radiologic hallmarks in CADASIL and decline in specific cognitive domains. METHODS: Twenty-five NOTCH3 mutation carriers and 13 controls had standardized neuropsychological testing and MRI examinations at baseline and after a follow-up of 7 years. To identify longitudinal associations between MRI abnormalities and cognitive decline, correlation analysis was used. RESULTS: At follow-up, mutation carriers showed a decline in global cognitive function (CAMCOG, p < 0.01) and in the cognitive domains language, memory, and executive function, compared to controls. Cognitive decline, especially executive dysfunction, was associated with increase in lacunar infarcts, microbleeds, and ventricular volume. In contrast, WMHs and brain atrophy were not associated with cognitive decline. CONCLUSION: Increase in lacunar infarcts, microbleeds, and ventricular volume, but not white matter lesions or atrophy, are associated with cognitive decline in the process of CADASIL in younger-aged, mildly affected patients with CADASIL.","Adult;Brain/blood supply/*pathology;Brain Infarction/epidemiology/genetics/pathology;CADASIL/epidemiology/genetics/*pathology;Cerebral Arteries/pathology/physiopathology;Cerebral Hemorrhage/epidemiology/genetics/pathology;Cerebral Ventricles/pathology/physiopathology;Cognition Disorders/epidemiology/genetics/*pathology;Cohort Studies;Comorbidity;DNA Mutational Analysis;Disease Progression;Female;Follow-Up Studies;Genetic Markers/genetics;Genetic Testing;Humans;Incidence;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/genetics;Neuropsychological Tests;Receptors, Notch/genetics","Liem, M. K.;Lesnik Oberstein, S. A.;Haan, J.;van der Neut, I. L.;Ferrari, M. D.;van Buchem, M. A.;Middelkoop, H. A.;van der Grond, J.",2009,Jan 13,10.1212/01.wnl.0000339038.65508.96,0,
2913,Cerebrovascular reactivity is a main determinant of white matter hyperintensity progression in CADASIL,"BACKGROUND AND PURPOSE: Basal total cerebral blood flow (TCBF) and cerebrovascular reactivity (CVR) are assumed to play an important role in the pathophysiology of small-vessel disease. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a unique monogenetic model to study the pathophysiology of arterial small-vessel disease. The aim of this study was to investigate the role of TCBF and CVR in the progression of MR imaging abnormalities in CADASIL. MATERIALS AND METHODS: Basal TCBF was measured in 25 NOTCH3 mutation carriers and 13 control subjects at baseline. CVR after administration of acetazolamide was measured in 14 NOTCH3 mutation carriers and 9 control subjects. Increase in white matter hyperintensities (WMHs), lacunar infarcts, and microbleeds on MR imaging was measured 7 years later. RESULTS: Lower CVR at baseline was associated with larger increase of WMHs (P = .001) but not with a larger increase of lacunar infarcts or microbleeds. TCBF at baseline was not associated with an increase of MR imaging abnormalities. CONCLUSIONS: Decreased CVR is a potential predictor of disease progression as indicated by increasing WMHs in CADASIL.","Adult;CADASIL/ complications/ pathology;Cerebrovascular Disorders/ complications/ diagnosis;Disease Progression;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Liem, M. K.;Lesnik Oberstein, S. A.;Haan, J.;Boom, R.;Ferrari, M. D.;Buchem, M. A.;Grond, J.",2009,Jun,10.3174/ajnr.A1533,0,
2914,Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects,"BACKGROUND AND PURPOSE: Incidental findings of infarcts on brain imaging are common, but their clinical significance is not clear. We examined the prevalence of symptomatic and silent infarcts on cranial computerized tomography (cCT) and their relation to dementia and mortality in a representative sample of 239 85-year-olds living in Gothenburg Sweden. METHODS: Information on stroke was obtained from an inpatient hospital linkage system, self-reports, and key informants. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd revision. Cortical and lacunar infarcts were diagnosed on cCT. RESULTS: The prevalence of cerebral infarcts was 17.1%, and half of those were clinically silent (8.6%). The frequency of dementia was increased in those with symptomatic (OR, 5.5; 95% CI, 2.1 to 14.1) and silent infarcts (OR, 2.7; 95% CI, 1.1 to 6.7). Infarcts increased the risk for dementia and its severity in women but not in men. The 3-year mortality rate was increased in those with symptomatic (OR, 4.0; 95% CI, 1.6 to 9.6) and silent infarcts (OR, 3.4; 95% CI, 1.4 to 8.5). CONCLUSIONS: Almost one fifth of 85-year-olds have infarcts on cCT, and half of those are clinically silent. These infarcts are related to an increased rate of dementia and 3-year mortality. Cerebrovascular disease as a cause of dementia may be underrated because of silent infarcts. It has to be elucidated whether treatment of risk factors for stroke may reduce the consequences of silent infarcts.","Aged;Aged, 80 and over;Brain Infarction/ complications/mortality/ radiography;Dementia/epidemiology/ etiology;Female;Humans;Male;Risk Factors;Survival Analysis;Tomography, X-Ray Computed","Liebetrau, M.;Steen, B.;Hamann, G. F.;Skoog, I.",2004,Aug,10.1161/01.str.0000131928.47478.44,0,
2915,[White matter lesions as a risk factor for stroke and dementia. A population-based study in 85-year-olds] Marklagerlasionen als Risikofaktor fur Schlaganfalle und Demenzen. Ergebnisse einer populationsbasierten Studie bei 85-Jahrigen,"AIM: This study was performed to determine whether white matter lesions on cranial computed tomography (cCT) are associated with increased prevalence and incidence of stroke, dementia, and mortality. METHODS: A representative sample of 239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based study. Stroke was defined by information from patient reports, key informants, and an inpatient register system. Dementia was diagnosed according to DSM-III-R. White matter lesions (WML) and infarcts were determined by cCT. Follow-up examinations were performed 3 years later. RESULTS: White matter lesions doubled the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke. CONCLUSION: White matter lesions are common in the elderly, and these changes have clinical consequences increasing the risk of stroke. Whether preventive mechanisms could lead to risk reduction should be clarified in further studies.","Aged;Aged, 80 and over;Comorbidity;Dementia/ diagnosis/ epidemiology;Female;Geriatric Assessment/methods/statistics & numerical data;Humans;Incidence;Male;Nerve Fibers, Myelinated/ diagnostic imaging/ pathology;Prognosis;Radiography;Risk Assessment/ methods;Risk Factors;Stroke/ diagnosis/ epidemiology;Sweden/epidemiology","Liebetrau, M.;Hamann, G. F.;Skoog, I.",2005,Jun,,0,
2916,[White matter lesions as a risk factor for stroke and dementia. A population-based study in 85-year-olds],"AIM: This study was performed to determine whether white matter lesions on cranial computed tomography (cCT) are associated with increased prevalence and incidence of stroke, dementia, and mortality. METHODS: A representative sample of 239 85-year-olds living in Gothenburg, Sweden, was examined in a population-based study. Stroke was defined by information from patient reports, key informants, and an inpatient register system. Dementia was diagnosed according to DSM-III-R. White matter lesions (WML) and infarcts were determined by cCT. Follow-up examinations were performed 3 years later. RESULTS: White matter lesions doubled the odds of previous stroke (OR 1.8, 95% CI 1.03-3.3). Individuals with WML and stroke showed higher prevalence of dementia (OR 16.5, 95% CI 6.5-41.8) and mortality (OR 12.4, 95% CI 5.1-30.0) than those without WML and stroke. CONCLUSION: White matter lesions are common in the elderly, and these changes have clinical consequences increasing the risk of stroke. Whether preventive mechanisms could lead to risk reduction should be clarified in further studies.","Aged;Aged, 80 and over;Comorbidity;Dementia/*diagnosis/*epidemiology;Female;Geriatric Assessment/methods/statistics & numerical data;Humans;Incidence;Male;Nerve Fibers, Myelinated/*pathology/*radiography;Prognosis;Risk Assessment/*methods;Risk Factors;Stroke/*diagnosis/*epidemiology;Sweden/epidemiology","Liebetrau, M.;Hamann, G. F.;Skoog, I.",2005,Jun,10.1007/s00115-004-1832-2,0,
2917,Binswanger's disease: some neuropsychological considerations,"The literature regarding Binswanger's disease is reviewed. Emphasis is placed on reviewing the neuropsychological literature related to Binswanger's disease. In addition, a retrospective analysis was carried out among four groups of subjects (N = 61) who were divided according to the presence or absence of dementia and deep white-matter alterations. A main effect for deep white-matter alterations was found for almost all measures of diastolic and systolic blood pressure. Among the two nondemented groups there was an effect of deep white matter alteration on neuropsychological functioning. Subjects with deep white matter changes performed worse on tests of immediate and delayed recall of a prose passage. Among the two demented groups there were no differences on any of the neuropsychological measures, although subjects with deep white matter alterations exhibited a higher incidence of focal neurologic signs and stroke. We conclude that Binswanger's disease is probably more prevalent than currently appreciated. Also, among clinically nondemented individuals periventricular white-matter alterations may be associated with subtle but definable neuropsychological deficits, and these individuals may be at risk for developing a dementing illness.","Aged;Alzheimer Disease/diagnosis/*psychology;Cerebral Ventricles/pathology;Dementia, Vascular/diagnosis/*psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;*Neuropsychological Tests;Tomography, X-Ray Computed","Libon, D. J.;Scanlon, M.;Swenson, R.;Coslet, H. B.",1990,Jan-Mar,,0,
2918,Linking MRI hyperintensities with patterns of neuropsychological impairment: evidence for a threshold effect,"BACKGROUND AND PURPOSE: Leukoaraiosis (LA) might interrupt intra- and interhemispheric communication and thus induce cognitive impairments and dementia. It remains unclear, however, if there is a volume threshold of LA that is needed before either the signs of dementia and/or a specific pattern of neuropsychological impairment become manifest. Roman et al has suggested that 25% of white matter may need to be involved before white matter alterations influence the clinical signs associated with dementia. The purpose of this study is to ascertain the threshold of MRI-LA as measured with a visual rating scale needed to induce specific patterns of neuropsychological impairment associated with dementia. METHODS: One hundred fifteen patients with dementia received a comprehensive neuropsychological examination and the severity of MRI-LA was measured using a 40-point LA scale. RESULTS: Patients were categorized into low (mean LA=4.21+/-2.92; 3.22%-17.82%), moderate (mean LA=12.58+/-2.54; 25.01%-37.80%), and severe (mean LA=22.36+/-4.04; 45.80%-66.00%) LA groups. Patients in the mild LA group obtained markedly lower scores on tests of episodic memory compared with working memory, a neuropsychological profile often associated with Alzheimer disease. Patients with moderate LA displayed equal impairment on neuropsychological tests. Patients in the severe LA group obtained significantly lower scores on tests of working memory as compared with episodic memory. CONCLUSIONS: These data provide evidence that a threshold of moderate MRI-LA as measured with a visual rating scale is associated with greater and/or equal impairment on tests of working memory versus episodic memory and provides a benchmark to assess the effect of MRI-LA on the clinical presentation of dementia.","Aged;Aged, 80 and over;Benchmarking;Cohort Studies;Dementia/diagnosis/*etiology;Differential Threshold;Humans;Leukoaraiosis/*diagnosis/*psychology;*Magnetic Resonance Imaging;Memory;Neuropsychological Tests;Psychiatric Status Rating Scales;Severity of Illness Index","Libon, D. J.;Price, C. C.;Giovannetti, T.;Swenson, R.;Bettcher, B. M.;Heilman, K. M.;Pennisi, A.",2008,Mar,10.1161/strokeaha.107.489997,0,
2919,Verbal memory and brain aging: an exploratory analysis of the role of error responses in the Framingham Study,"OBJECTIVE: Analysis sought to determine whether Wechsler Memory Scale-Logical Memory (LM)-correct responses and errors were related to magnetic resonance imaging (MRI) brain volume measurements. METHODS: The LM immediate (LM-I) and LM delay (LM-D) free recall correct responses and related and unrelated errors were scored. Principal components analysis yielded a 3-factor solution: LM-I and LM-D correct responses, LM-I and LM-D-unrelated errors, and LM-I/-D-related errors. The MRI total cerebral brain volume, frontal brain volume, temporal horn volume (THV), and white matter hyperintensities volume (WMHIV) were obtained. RESULTS: Increasing THV (suggesting greater regional atrophy) was associated with lower scores on the LM-correct responses factor. Extensive WMHIV was associated with higher scores on the LM-related errors factor. CONCLUSION: These results suggest that LM-correct responses could relate to emerging brain alterations. Longitudinal research might enhance the sensitivity of this test to identify preclinical impairment and persons at risk of mild cognitive impairment and dementia.",,"Libon, D. J.;Preis, S. R.;Beiser, A. S.;Devine, S.;Seshadri, S.;Wolf, P. A.;DeCarli, C.;Au, R.",2015,Sep,10.1177/1533317515577184,0,
2920,Neuropsychological profiles associated with subcortical white matter alterations and Parkinson's disease: implications for the diagnosis of dementia,"Despite the emergence of a number of new classification systems, the diagnosis of cerebrovascular dementia remains controversial. Also controversial is the significance of periventricular and deep white matter alterations (WMA) as seen on magnetic resonance imaging (MRI). To further clarify this issue, MRI scans were used to regroup patients clinically diagnosed with Alzheimer's disease (AD) or subcortical ischemic vascular dementia (IVD) into cohorts presenting with either little versus significant WMA on MRI. These two groups were then compared to demented patients diagnosed with idiopathic Parkinson's disease (PD) using a comprehensive neuropsychological protocol. Neuropsychological assessment failed to distinguish between patients with PD and significant WMA. By contrast, both of these patient groups exhibited disproportionate impairment on tests of executive systems functioning, whereas patients with little WMA showed greater impairment on tests of declarative memory and semantic knowledge. These findings constitute further evidence that the pattern of cognitive impairment associated with significant WMA is distinctly different when compared to AD. These results are discussed within the context of a growing body of literature suggesting that elements of the underlying neuropathologies in AD and IVD are linked. Implications for the diagnosis of dementia are also discussed.",,"Libon, D. J.;Bogdanoff, B.;Leopold, N.;Hurka, R.;Bonavita, J.;Skalina, S.;Swenson, R.;Gitlin, H. L.;Ball, S. K.",2001,Jan,,0,
2921,"Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia","This research investigated whether subjects with Alzheimer's disease (AD) and ischaemic vascular dementia (IVD) associated with periventricular and deep white matter alterations can be dissociated on tests of declarative and procedural memory, as well as on MRI indices of white matter alterations and the size of the hippocampal formation. The California Verbal Learning Test (CVLT) and the Pursuit Rotor Learning Tests (PRLT) were used to measure declarative and procedural memory, respectively. Subjects with IVD obtained a higher score on the CVLT recognition discriminability index; however, on the PRLT total time on target, carry-over between trial blocks, and slope calculated for all test trials was low. Subjects with AD exhibited the opposite profile. MRI studies indicated that subjects with IVD had considerably greater white matter alterations, but larger hippocampal formations than subjects with AD. Higher scores on the CVLT recognition discriminability index were correlated with increased size of the body of the hippocampus and parahippocampal gyrus. By contrast, as the severity of white matter alterations increased the slope on the PRLT declined. In sum, subjects with AD and IVD can be dissociated on the basis of differing patterns of impairment on tests of declarative and procedural memory, and MRI indices of white matter alteration and the integrity of the hippocampal formation.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/physiopathology;Attention/physiology;Cerebral Ventricles/pathology;Dementia, Multi-Infarct/*diagnosis/physiopathology;Female;Hippocampus/*pathology;Humans;*Magnetic Resonance Imaging;Male;Mental Recall/*physiology;Neuropsychological Tests;Psychomotor Performance/*physiology;Reference Values;Verbal Learning/*physiology","Libon, D. J.;Bogdanoff, B.;Cloud, B. S.;Skalina, S.;Giovannetti, T.;Gitlin, H. L.;Bonavita, J.",1998,Feb,10.1076/jcen.20.1.30.1490,0,
2922,Characterization of CADASIL among the Han Chinese in Taiwan: Distinct genotypic and phenotypic profiles,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is originally featured with a strong clustering of mutations in NOTCH3 exons 3-6 and leukoencephalopathy with frequent anterior temporal pole involvement. The present study aims at characterizing the genotypic and phenotypic profiles of CADASIL in Taiwan. One hundred and twelve patients with CADASIL from 95 families of Chinese descents in Taiwan were identified by Sanger sequencing of exons 2 to 24 of NOTCH3. Twenty different mutations in NOTCH3 were uncovered, including 3 novel ones, and R544C in exon 11 was the most common mutation, accounting for 70.5% of the pedigrees. Haplotype analyses were conducted in 14 families harboring NOTCH3 R544C mutation and demonstrated a common haplotype linked to NOTCH3 R544C at loci D19S929 and D19S411. Comparing with CADASIL in most Caucasian populations, CADASIL in Taiwan has several distinct features, including less frequent anterior temporal involvement, older age at symptom onset, higher incidence of intracerebral hemorrhage, and rarer occurrence of migraine. Subgroup analyses revealed that the R544C mutation is associated with lower frequency of anterior temporal involvement, later age at onset and higher frequency of cognitive dysfunction. In conclusion, the present study broadens the spectrum of NOTCH3 mutations and provides additional insights for the clinical and molecular characteristics of CADASIL patients of Han-Chinese descents.",Notch3 receptor;adult;article;brain hemorrhage;CADASIL;Caucasian;clinical feature;cognitive defect;controlled study;exon;female;gene frequency;gene locus;genotype;Han Chinese;haplotype;human;incidence;major clinical study;male;migraine;mutational analysis;neuroimaging;NOTCH3 gene;nuclear magnetic resonance imaging;onset age;pedigree;phenotype;senescence;sequence analysis;symptom;Taiwan,"Liao, Y. C.;Hsiao, C. T.;Fuh, J. L.;Chern, C. M.;Lee, W. J.;Guo, Y. C.;Wang, S. J.;Lee, I. H.;Liu, Y. T.;Wang, Y. F.;Chang, F. C.;Chang, M. H.;Soong, B. W.;Lee, Y. C.",2015,,,0,
2923,Discerning mild cognitive impairment and Alzheimer Disease from normal aging: morphologic characterization based on univariate and multivariate models,"RATIONALE AND OBJECTIVES: Differentiating mild cognitive impairment (MCI) and Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed to explore the cerebral structural alterations of subjects with MCI or AD as compared to healthy elderly based on the individual and collective effects of cerebral morphologic indices using univariate and multivariate analyses. MATERIALS AND METHODS: T1-weighted images (T1WIs) were retrieved from Alzheimer Disease Neuroimaging Initiative database for 116 subjects who were categorized into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) were performed to explore the intergroup morphologic alterations indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume with age and sex controlled as covariates, in 34 parcellated gyri regions of interest (ROIs) for both cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the anatomic images to facilitate visual inspection. RESULTS: Global rather than region-specific structural alterations were revealed in groups of MCI and AD relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical thickness decreased more prominently in entorhinal, temporal, and cingulate cortices and was positively correlated with patients' cognitive performance in AD group but not in MCI. The temporal lobe features marked atrophy of white matter during the disease dynamics. Significant intercorrelations were observed among the morphologic indices with univariate analysis for given ROIs. CONCLUSIONS: Significant global structural alterations were identified in MCI and AD based on MANCOVA model with improved sensitivity. The intercorrelation among the morphologic indices may dampen the use of individual morphological parameter in featuring cerebral structural alterations. Decrease in cortical thickness is not reflective of the cognitive performance at the early stage of AD.","Aged;Aging/ pathology;Algorithms;Alzheimer Disease/complications/ pathology;Brain/ pathology;Computer Simulation;Diagnosis, Differential;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/complications/ pathology;Models, Statistical;Multivariate Analysis;Pattern Recognition, Automated/methods;Reference Values;Reproducibility of Results;Sensitivity and Specificity","Liao, W.;Long, X.;Jiang, C.;Diao, Y.;Liu, X.;Zheng, H.;Zhang, L.",2014,May,10.1016/j.acra.2013.12.001,0,
2924,Microstructural white matter abnormalities independent of white matter lesion burden in amnestic mild cognitive impairment and early Alzheimer disease among Han Chinese elderly,"This study was designed to evaluate the microstructural integrity of white matter (WM) in amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Han Chinese elderly using diffusion tensor imaging (DTI) technique, and to investigate the relationship between WM abnormalities and cognitive dysfunction. Sixty-four subjects (23 mild probable AD, 20 amnestic MCI, and 21 age-matched normal controls) who did not have visible WM lesion burden were analyzed. Fractional anisotropy (FA) and mean diffusivity were measured in normal-appearing WM (NAWM) using DTI with 64 encoding directions. The results were correlated with the scores of Mini-Mental State Examination (MMSE) and Cognitive Ability Screening Instrument (CASI). Statistical analysis showed the FA value in parietal WM was significantly lower in MCI compared to NC (P<0.001), and further decreased in AD compared to MCI (P=0.005). The lower FA and elevated mean diffusivity values were found in temporal WM, frontal WM, parahippocampal and posterior cingulate fibers of AD group compared to MCI and NC (all P<0.01). Canonical correlation analysis showed that the parietal FA values measured from all subjects were significantly correlated with the scores of CASI and MMSE (P<0.01). The results indicated that DTI can detect microstructural WM abnormalities in AD and amnestic MCI, and the measures were correlated with cognitive performance. In MCI, the abnormality was found to be limited within the parietal WM; and in AD a more widespread alteration was found in other brain regions as well. Copyright © 2010 by Lippincott Williams & Wilkins.",,"Liao, J.;Zhu, Y.;Zhang, M.;Yuan, H.;Su, M. Y.;Yu, X.;Wang, H.",2010,October-December,,0,
2925,Preclinical Cerebral Network Connectivity Evidence of Deficits in Mild White Matter Lesions,"White matter lesions (WMLs) are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer's disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity (FC) of three resting-state networks (RSNs) related to the changed cognitive domains: the default mode network (DMN) and the bilateral fronto-parietal network (FPN). We also performed voxel-based morphometry analysis to compare whole-brain gray matter (GM) volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between FC and structural connectivity. We observed FC alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant GM atrophy difference was found. Furthermore, the right precuneus FC in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance.",,"Liang, Y.;Sun, X.;Xu, S.;Liu, Y.;Huang, R.;Jia, J.;Zhang, Z.",2016,,10.3389/fnagi.2016.00027,0,
2926,Sex Moderates the Effects of the Sorl1 Gene rs2070045 Polymorphism on Cognitive Impairment and Disruption of the Cingulum Integrity in Healthy Elderly,"The SORL1 rs2070045 polymorphism was reported to be associated with SorLA expression in the brain and the risk of late-onset Alzheimer’s disease (AD). However, the influence of this polymorphism on cognitive functioning is likely to be moderated by sex. This study aimed to examine the sex moderation on the effects of rs2070045 on neuropsychological performance and the cingulum integrity in Chinese Han population. In this study, 780 non-demented older adults completed a battery of neuropsychological scales. Diffusion tensor images (DTI) of 126 subjects were acquired. We adopted the atlas-based segmentation strategy for calculating the DTI indices of the bilateral cingulum and cingulum hippocampal part for each subject. We used a multivariate analysis of variance (MANOVA) to compare the cognitive performance and DTI differences between the rs2070045 genotype. Controlling for age, education, and the APOE ɛ4 status, the influence of sex on the effects of the rs2070045 polymorphism on executive function was observed. We also found an interaction between sex and the rs2070045 polymorphism on the white matter (WM) microstructure of the left cingulum hippocampal part. Furthermore, the mean diffusivity and axial diffusivity of the tract were associated with Trail Making Test performance in T/T men. These results hint that sex moderates the association between the rs2070045 polymorphism and executive function, as well as the WM integrity of the left cingulum hippocampal part. Our findings underscore the importance of considering the influence of sex when examining the candidate genes for cognitive abilities and AD.Neuropsychopharmacology advance online publication, 4 February 2015; doi:10.1038/npp.2015.1.",adult;aged;brain;cognitive defect;diffusion;education;executive function;gene;genotype;human;male;multivariate analysis of variance;population;psychologic test;risk;task performance;white matter,"Liang, Y.;Li, H.;Lv, C.;Shu, N.;Chen, K.;Li, X.;Zhang, J.;Hu, L.;Zhang, Z.",2015,,10.1038/npp.2015.1,0,2927
2927,Sex moderates the effects of the Sorl1 gene rs2070045 polymorphism on cognitive impairment and disruption of the cingulum integrity in healthy elderly,"The SORL1 rs2070045 polymorphism was reported to be associated with SorLA expression in the brain and the risk of late-onset Alzheimer's disease (AD). However, the influence of this polymorphism on cognitive functioning is likely to be moderated by sex. This study aimed to examine the sex moderation on the effects of rs2070045 on neuropsychological performance and the cingulum integrity in Chinese Han population. In this study, 780 non-demented older adults completed a battery of neuropsychological scales. Diffusion tensor images (DTI) of 126 subjects were acquired. We adopted the atlas-based segmentation strategy for calculating the DTI indices of the bilateral cingulum and cingulum hippocampal part for each subject. We used a multivariate analysis of variance (MANOVA) to compare the cognitive performance and DTI differences between the rs2070045 genotype. Controlling for age, education, and the APOE varepsilon4 status, the influence of sex on the effects of the rs2070045 polymorphism on executive function was observed. We also found an interaction between sex and the rs2070045 polymorphism on the white matter (WM) microstructure of the left cingulum hippocampal part. Furthermore, the mean diffusivity and axial diffusivity of the tract were associated with Trail Making Test performance in T/T men. These results hint that sex moderates the association between the rs2070045 polymorphism and executive function, as well as the WM integrity of the left cingulum hippocampal part. Our findings underscore the importance of considering the influence of sex when examining the candidate genes for cognitive abilities and AD.","Age Factors;Aged;Aged, 80 and over;Apolipoprotein E4/genetics;Brain/ pathology;Cognition Disorders/ genetics/ pathology;Diffusion Tensor Imaging;Educational Status;Female;Humans;LDL-Receptor Related Proteins/ genetics;Longitudinal Studies;Male;Membrane Transport Proteins/ genetics;Middle Aged;Nerve Fibers, Myelinated/pathology;Neural Pathways/pathology;Neuropsychological Tests;Polymorphism, Genetic;Polymorphism, Single Nucleotide;Sex Characteristics","Liang, Y.;Li, H.;Lv, C.;Shu, N.;Chen, K.;Li, X.;Zhang, J.;Hu, L.;Zhang, Z.",2015,May,10.1038/npp.2015.1,0,
2928,Disrupted functional connectivity related to differential degeneration of the cingulum bundle in mild cognitive impairment patients,"Previous studies have demonstrated that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) exhibited anatomical and functional abnormalities in the anterior cingulate cortex (ACC) and accumulating evidence supported the hypothesis that changes in the ACC predict the progression from aMCI to AD. In this study, we aimed to explore how the two functional and structural heterogeneous sub-regions of ACC, namely the dorsal ACC (dACC) and the ventral ACC (vACC), changed in aMCI and whether the structural connectivity affects the functional connectivity between the two ACC subregions. To investigate this hypothesis, we studied resting-state fMRI and DTI images in a group of 24 aMCIs and 29 healthy controls. The dACC exhibited a significantly increased functional connectivity in the Salience Network (SN) and a decreased functional connectivity with the vACC in aMCI. The DTI results showed that the bilateral cingulum fibers were the most damaged tracts in aMCI and that the fractional anisotrophy of the left anterior cingulum was significantly correlated with the functional connectivity between the two ACC sub-regions. In conclusion, this study revealed the pathological changes in the intrinsic functional connectivity of the ACC within SN, as well as the connectivity between the dACC and vACC in aMCI. Our study also revealed that disrupted white matter integrity of the anterior regions of the cingulum was associated with the alterations in subregional connectivity in the ACC.","Aged;Aged, 80 and over;Diffusion Magnetic Resonance Imaging;Female;Gyrus Cinguli/blood supply/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ pathology;Neural Pathways/ blood supply/ pathology;Oxygen/blood;Principal Component Analysis","Liang, Y.;Chen, Y.;Li, H.;Zhao, T.;Sun, X.;Shu, N.;Peng, D.;Zhang, Z.",2015,,,0,
2929,A contrast between the cognitive function of patients with simple leukoaraeosis and subcortical arterioselerotic encephalopathy,"Background: Cognitive function of simple leukoaraeosis (LA) and subcortical arterioselerotic encephalopathy (SAE) is a part of research in cerebrovascular neuropsychology, however, there is no contrast study on cognitive function between the two diseases. Objective: To investigate the different features in cognitive function among patients with simple leukoaraeosis, subcortical arterioselerotic encephalopathy and simple leukoaraeosis combined with cerebral infarction. Design: Randomized controlled observation. Setting: Depar tment of Neur ological Medicine, Qilu Hospital, Shandong University. Participants: A total of 91 cases of patients with cerebrov ascular disease diagnosed in Department of Neurological Medicine of Qilu Hospital of Shandong University from March 1997 to May 2000 were selected. All the patients participated in the observation voluntarily. They were divided into 3 groups according to the type of disease, with 27 cases in simple leukoaraeosis group, 33 cases in subcortical arterioselerotic encephalopathy group and 31 cases in simple leukoaraeosis + cerebral infarction group. Additionally, 30 healthy cases were selected as control group. All the subjects in the above groups participated in the observation voluntarily. Methods: Assessment on cognitive function and memory ability was conducted on the subjects in each group, and contrast analysis was performed. Mini-mental state examination was used for detecting cognitive function. Patients whose score was less than 17, 20, 22, 23 respectively according to different educational degree (illiteracy, primary school, middle school, university), would be diagnosed as dementia. Clinical memory scale A edited by Psychology Institute of Chinese Academy of Medical Sciences was used for detecting memory ability including associative learning, directive memory, recognition of nonsense figure, image free recall and portrait characteristics associative recall. Conversed the above 5 items of detecting results to scores of scales and calculated out the memory quotients. Main outcome measures: State of cognitive disorder and scores of mini-mental state examination and clinical memory scale of subjects in each group. Results: All the 91 cases of patients with cerebrovascular disease and 30 healthy control cases entered results analysis without any drop out. 1 Comparison of the state of cognitive disorder among subjects in each group: There were 21 cases of mild cognitive disorder (77.8%) in simple leukoaraeosis group, 8 cases of moderate cognitive disorder (24.2%) and 25 cases of dementia (75.8%) in subcortical arterioselerotic encephalopathy group, 6 cases of moderate cognitive disorder (19.4%) and 24 cases of dementia (77.4%) in simple leukoaraeosis + cerebral infarction group. 2 Comparison of the scores of mini-mental state examination among and clinical memory scale: Scores of the two scales in simple leukoaraeosis group, subcortical arterioselerotic encephalopathy group and simple leukoaraeosis + cerebral infarction group were significantly lower than those in healthy control group (t=2.14-3.81, P < 0.05-0.01). The scores in subcortical arterioselerotic encephalopathy group and simple leukoaraeosis + cerebral infaretion group were significantly lower than those in simple leukoaraeosis group (t=2.13-3.37, P < 0.05-0.01). Conclusion: 1 The cognitive impairment in simple leukoaraeosis is mainly mild cognitive disorder. 2 The cognitive impairments in subcortical arterioselerotic encephalopathy and simple leukoaraeosis + cerebral infarction are mainly moderate cognitive disorder and dementia which are obviously severer than mild cognitive disorder. Cognitive function can be used as reference indicator for assessing simple leukoaraeosis and subcortical arterioselerotic encephalopathy.",,"Liang, L. P.;He, Y.;Guo, H. Z.",2006,15,,0,
2930,Spontaneous intracerebral hemorrhage in CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary small vascular disease and its mainly clinical manifestations are ischemic events. Spontaneous intracerebral hemorrhage (ICH) involvement in patients with CADASIL is extremely uncommon.CASE REPORT: A 46-year-old normotensive Chinese man developed a large hematoma in the left basal ganglia after he was diagnosed with CADASIL 2 months ago, the patient did not take any antithrombotics. Susceptibility weighted imaging at pre-ICH showed multiple cerebral microbleeds (CMBs) in the bilateral basal ganglia. He experienced migraine at about 10 months post-ICH. To our knowledge, this is the first report of ICH in CADASIL patients with Arg90Cys mutation in exon 3.DISCUSSION AND CONCLUSIONS: ICH should be considered when evaluating new attacks in CADASIL patients. Thus, MRI screening for CMBs might be helpful in predicting the risk of ICH and guiding antithrombotic therapy. In addition, strict control of hypertension and cautious use of antithrombotics may be important in this context.",,"Lian, L.;Li, D.;Xue, Z.;Liang, Q.;Xu, F.;Kang, H.;Liu, X.",2013,2013,,0,
2931,18F-Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral beta-Amyloid Plaques,"Early noninvasive visualization of cerebral beta-amyloid (Abeta) plaques with positron emission tomography (PET) is the most feasible way to diagnose Alzheimer's disease (AD). In this study, a series of flexible benzyldiamine derivatives (BDA) were proposed for binding to aggregated beta-amyloid 1-42 (Abeta1-42) with high adaptability, high binding affinity (6.8 +/- 0.6 nM), and rapid body excretion. The methylthio (12) and ethoxyl (10) derivatives were further labeled with 18F directly on their benzene ring and examined as PET probes for Abeta plaque imaging. [18F]12 displayed 4.87 +/- 0.52% ID/g initial uptake and prompt washout from normal brain in biodistribution studies. MicroPET-CT imaging indicated sufficient retention of [18F]12 but lower white matter uptake in the brain of an AD transgenic mouse model compared with that of commercial [18F]AV-45. Our experimental results provide new insights for developing targeting ligands possessing a flexible framework for use as efficient Abeta probes for PET imaging of AD brain.",,"Li, Z.;Zhang, X.;Zhang, X.;Cui, M.;Lu, J.;Pan, X.;Zhang, X.",2016,Dec 08,,0,
2932,MR diffusion tensor imaging voxel-based analysis of whole brain white matter in patients with amnestic-type mild cognitive impairment and mild Alzheimer disease,"Objective: To evaluate the microstructural integrity of white matter(WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter (GM) atrophy. Methods: Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results: Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the WM adjacent to the triangular part of the right lateral ventricle (k ≥ 20 voxels). In mild AD, significantly reduced FA value was found in bilateral hippocampal, inferior parietal lobular, frontal, temporal, and occipital WM, bilateral corpus callosum, anterior part of cingulums, the WM adjacent to the triangular part of the bilateral lateral ventricles, left temporal stem, left thalamus, right precuneus (k ≥ 20 voxels). Significantly reduced GM volume was found in left hippocampus, parahippocampal gyrus, lingual gyrus and superior temporal gyrus, bilateral insulae and middle temporal gyri in aMCI group when compared with control group (k ≥ 50 voxels). In mild AD, significantly reduced GM volume was found in bilateral hippocampi, parahippocampal gyri, amygdalae, thalami, temporal, parietal, frontal, occipital cortex (k ≥ 50 voxels). The pattern of areas with reduced",,"Li, Y. D.;Feng, X. Y.;He, H. J.;Ding, D.;Tang, W. J.;Zhao, Q. H.",2011,April,,0,
2933,Neuron-specific enolase in patients with acute ischemic stroke and related dementia,Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in acute ischemic stroke patients as compared with the controls. The altered CSF NSE levels correlated well with the infarct size in CT scan. The CSF NSE levels were higher in 6-multiinfarct dementia (MID) patients who were diagnosed after 6-month follow-up than those in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE in the study of dementia related to ischemic stroke is worth further studies.,"Aged;Biomarkers/cerebrospinal fluid;Cerebrovascular Disorders/complications/*enzymology;Dementia, Multi-Infarct/*enzymology/etiology;Female;Humans;Male;Middle Aged;Phosphopyruvate Hydratase/*cerebrospinal fluid","Li, Y.;Wang, X.;Yang, Z.",1995,Mar,,0,
2934,Cortical laminar binding of PET amyloid and tau tracers in Alzheimer disease,"Neurofibrillary tau pathology and amyloid beta (Abeta) plaques, characteristic lesions of Alzheimer disease (AD), show different neocortical laminar distributions. Neurofibrillary-tangle tau pathology tends to be closer to the gray matter-white matter boundary, whereas Abeta is dispersed throughout the width of the cortical ribbon. METHODS: Using PET radiotracers for tau and Abeta lesions, we developed an image analysis tool to measure the distance of tracer-positive voxels from the gray matter-white matter boundary. We studied 5 AD and 5 healthy subjects with both (18)F-THK5117 (tau) and (11)C-Pittsburgh compound B (Abeta) PET. RESULTS: On average, tau-positive voxels were closer to the white matter than were Abeta-positive voxels. This effect was found for all AD subjects and for all regions, both before and after regionally adjusting for the nonspecific white matter binding of both tracers. The differential laminar pattern was validated through postmortem examination. CONCLUSION: Within cortical lamina, distance measures may be of value in testing PET tracers for their anatomic selectivity.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ radionuclide imaging;Amyloid/ chemistry;Amyloid beta-Peptides/ chemistry;Biomarkers, Tumor/chemistry;Carbon Radioisotopes/chemistry;Cerebral Cortex/radionuclide imaging;Disease Progression;Female;Fluorine Radioisotopes/chemistry;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neurofibrillary Tangles/radionuclide imaging;Positron-Emission Tomography;tau Proteins/ chemistry","Li, Y.;Tsui, W.;Rusinek, H.;Butler, T.;Mosconi, L.;Pirraglia, E.;Mozley, D.;Vallabhajosula, S.;Harada, R.;Furumoto, S.;Furukawa, K.;Arai, H.;Kudo, Y.;Okamura, N.;de Leon, M. J.",2015,Feb,10.2967/jnumed.114.149229,0,
2935,Association of Notch3 single-nucleotide polymorphisms and lacunar infarctions in patients,"Cerebrovascular disease is a leading cause of morbidity and mortality worldwide, which is influenced by genetic and environmental factors. The aim of the present study was to examine the association between single‑nucleotide polymorphisms (SNPs) in Notch3 exons 3‑6 and lacunar infarction by comparing SNPs between control subjects and those with lacunar infarction. A single‑center case‑control study was conducted to investigate the association between Notch3 SNPs and risk of stroke. A total of 140 patients were included in the study, 30 of whom had no infarction (control) and 110 had lacunar infarction. Lacunar patients were divided into the ‘pure lacunar’ and ‘lacunar + leukoarasis’ groups based on brain imaging. All the patients were of Chinese Han ethnicity, and the male to female ratio was 84:56. Patient clinical histories included hypertension, diabetes mellitus (DM), hyperlipidemia, and heart disease were recorded. The Notch3 sequence was obtained from the National Centser for Biotechnology Information database. Notch3 was amplified by polymerase chain reaction from whole blood samples, and exons 3‑6 were sequenced to identify SNPs. The result showed that there was no significant difference in the prevalence of hypertension, DM, hyperlipidemia, and heart disease between the control and lacunar infarction patients. Notabley, the age of the lacunar + leukoarasis patients was significantly higher than that of the control and pure lacunar patients (P<0.05). Eight SNPs were detected at low frequencies, and only rs3815388 and rs1043994 exhibited slightly higher frequencies. A χ(2) test indicated that Notch3 SNPs, particularly rs1043994, were associated with lacunar infarction (P<0.05). In conclusion, the result of the present study have shown that Notch3 SNPs, particularly rs1043994, are associated with lacunar infarction.",,"Li, Y.;Liu, N.;Chen, H.;Huang, Y.;Zhang, W.",2016,1,,0,
2936,White matter degeneration in subjective cognitive decline: A diffusion tensor imaging study,"Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3±8.0), 35 aMCI (age=69.2±8.6) and 25 AD patients (age=68.3±9.4) and 37 normal controls (NC) (age=65.1±6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p < 0.05), increased mean diffusivity (MD; p < 0.05), and increased radial diffusivity (RD; p < 0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p < 0.05) similar to what was observed in aMCI and AD patients (p < 0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=-0.333, p=0.045), MD (r=-0.351, p=0.03) and RD (r=-0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience.",adult;aged;aging;Alzheimer disease;article;axial diffusivity;brain degeneration;cognitive defect;controlled study;diffusion tensor imaging;female;fractional anisotropy;human;image analysis;major clinical study;male;mean diffusivity;memory disorder;mild cognitive impairment;neuropsychological test;nuclear magnetic resonance scanner;physical parameters;radial diffusivity;recall;white matter;Magnetom Trio Tim,"Li, X. Y.;Tang, Z. C.;Sun, Y.;Tian, J.;Liu, Z. Y.;Han, Y.",2016,,10.18632/oncotarget.10091,0,2937
2937,White matter degeneration in subjective cognitive decline: a diffusion tensor imaging study,"Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3+/-8.0), 35 aMCI (age=69.2+/-8.6) and 25 AD patients (age=68.3+/-9.4) and 37 normal controls (NC) (age=65.1+/-6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=-0.333, p=0.045), MD (r=-0.351, p=0.03) and RD (r=-0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience.",diffusion tensor imaging;preclinical Alzheimer's disease;subjective cognitive decline;tract-based spatial statistics;white matter,"Li, X. Y.;Tang, Z. C.;Sun, Y.;Tian, J.;Liu, Z. Y.;Han, Y.",2016,Jun 15,10.18632/oncotarget.10091,0,
2938,White matter changes in familial Alzheimer's disease,"BACKGROUND: Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain. OBJECTIVE: The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD. SUBJECTS: Ten mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre-MCs). METHODS: Whole-brain GM volume as well as fractional anisotropy (FA) and mean diffusivity (MD) using voxel-based morphometry and tract-based spatial statistics analyses, respectively, were compared between MCs and NCs. FA and MD maps were obtained from diffusion tensor imaging. RESULTS: A significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre-MCs compared with NCs. After inclusion of the three symptomatic MCs in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Abeta42, and positive correlations with P-tau181p and T-tau. No differences were observed in GM volume and FA between the groups. CONCLUSIONS: The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF, with similar patterns previously observed in sporadic Alzheimer's disease.",Adult;Alzheimer Disease/ diagnosis/genetics;Diffusion Magnetic Resonance Imaging/ methods;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology,"Li, X.;Westman, E.;Stahlbom, A. K.;Thordardottir, S.;Almkvist, O.;Blennow, K.;Wahlund, L. O.;Graff, C.",2015,Aug,10.1111/joim.12352,0,
2939,Tract-based spatial statistical analysis of Alzheimer's disease and its correlation with cognition scores,"Objective: To observe microstructural changes of white matter in Alzheimer's disease (AD), and to find out the relationship between white matters lesion and declined cognition. Methods: Twenty-four AD patients and 24 controls with normal cognition performed diffusion tensor imaging MR scan. Tract-based spatial statistical analysis (TBSS) was used to investigate microstructural change of white matter, and then its correlation with Mini-Mental State Examination (MMSE) scores was analyzed. Results: Fractional anisotropy (FA) values were decreased in corpus callosum, fornix, left corticospinal tract, bilateral cerebral peduncle, superior cerebellar peduncle, internal capsule, corona radiata, posterior thalamic radiation, sagittal stratum including inferior longitidinal fasciculus and inferior fronto-occipital fasciculus, external capsule, cingulate gyrus, hippocampus, superior longitudinal fasciculus and uncinate fasciculus, while mean diffusivity (MD) values were increased in fornix, left hippocampus, bilateral internal capsule, corona radiata, posterior thalamic radiation, sagittal stratum including inferior longitidinal fasciculus and inferior fronto-occipital fasciculus, external capsule, cingulate gyrus, superior longitudinal fasciculus, superior fronto-occipital fasciculus and uncinate fasciculus (all P < 0.05, threshold-free cluster enhancement corrected). MMSE scores had a positive correlation with decreased FA values of left sagittal stratum (r = 0.535, P = 0.007) and negative correlations with increased MD values of left sagittal stratum (r = - 0.427, P = 0.037), left superior longitudinal fasciculus (r = - 0.424, P = 0.039) and left uncinate fasciculus (r= -0.505, P =0.012). Conclusions: There exist widespread white matter lesions in AD with impairment of white matter connections of intra- and inter-hemispheres. Impaired white matters in left hemisphere may have close relationships with cognition decline.",Alzheimer disease;article;brain fornix;capsula interna;cerebral peduncle;cingulate gyrus;clinical article;cognition;controlled study;corona radiata (brain);corpus callosum;diffusion tensor imaging;external capsule;fractional anisotropy;hippocampus;human;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;occipitofrontal fasciculus;pyramidal tract;statistical analysis;superior cerebellar peduncle;superior longitudinal fasciculus;thalamus posterior nucleus;uncinate fasciculus;white matter;white matter lesion,"Li, X.;Wang, H.;Yu, Y.;Tian, Y.;Zhou, S.;Xu, L.;Li, X.",2016,,,0,
2940,Impaired White Matter Connections of the Limbic System Networks Associated with Impaired Emotional Memory in Alzheimer's Disease,"Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM) in mild cognitive impairment (MCI) and early Alzheimer's disease (AD) patients.In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM). Objective: To observe whether EEM is absent in amnestic MCI (aMCI) and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM) of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI) of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body), left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM connections and GM volumes of those networks are associated with impaired emotional memory and EEM effect in AD patients.",Alzheimer disease;diffusion tensor imaging;emotional enhancement of memory;mild cognitive impairment;tract-based spatial statistics;voxel-based morphometry,"Li, X.;Wang, H.;Tian, Y.;Zhou, S.;Li, X.;Wang, K.;Yu, Y.",2016,,,0,
2941,An enhanced voxel-based morphometry method to investigate structural changes: application to Alzheimer's disease,"INTRODUCTION: When characterizing regional cerebral gray matter differences in structural magnetic resonance images (sMRI) by voxel-based morphometry (VBM), one faces a known drawback of VBM, namely that histogram unequalization in the intensity images introduces false-positive results. METHODS: To overcome this limitation, we propose to improve VBM by a new approach (called eVBM for enhanced VBM) that takes the histogram distribution of the sMRI into account by adding a histogram equalization step within the VBM procedure. Combining this technique with two most widely used VBM software packages (FSL and SPM), we studied GM variability in a group of 62 patients with Alzheimer's disease compared to 73 age-matched elderly controls. RESULTS: The results show that eVBM can reduce the number of false-positive differences in gray matter concentration. CONCLUSION: Because it takes advantage of the properties of VBM while improving sMRI histogram distribution at the same time, the proposed method is a powerful approach for analyzing gray matter differences in sMRI and may be of value in the investigation of sMRI gray and white matter abnormalities in a variety of brain diseases.","Aged;Algorithms;Alzheimer Disease/ pathology;Brain/ pathology;False Positive Reactions;Female;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Software","Li, X.;Messe, A.;Marrelec, G.;Pelegrini-Issac, M.;Benali, H.",2010,Mar,10.1007/s00234-009-0600-1,0,
2942,Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients,"Some previous reports have suggested that hypertension is a risk factor for dementia and cognitive impairments. Using behavioral data from 1007 elderly human subjects (405 hypertensive patients) of Han ethnicity from Beijing, China, the present study aimed to assess the effects of hypertension on cognitive performance and explore related neuronal changes via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 84 of these subjects (44 hypertensive patients). Cognitively, we found that patients with hypertension showed decreased executive functions and attention compared with those with normotension in the large sample. In magnetic resonance imaging scan sample, using independent component analysis to examine the functional connectivity difference between the two groups, we found that the frontoparietal networks in the hypertensive group exhibited altered patterns compared with the control group, mainly in the inferior parietal lobe, left inferior frontal lobe, and precuneus. Using tract-based spatial statistics to investigate the between-group structural difference, we found that the hypertensive group showed significantly reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, using the mediation analysis, we found that the functional connectivity of the frontoparietal networks mediates the impact of white matter on executive function in the hypertensive group. The results demonstrate that hypertension targets a specific pattern of cognitive decline, possibly due to deficits in the white matter and functional connectivity in frontal and parietal lobes. Our findings highlight the importance of brain protection in hypertension. SIGNIFICANCE STATEMENT: Hypertension is a risk factor for cognitive decline and dementia. However, the neural mechanism underlying cognitive decline in hypertension is largely unknown. We studied the relationship among cognitive decline, brain functional, and structural changes in hypertensive patients via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data in a Chinese cohort. Hypertensive patients showed executive dysfunction, along with disrupted functional connectivity in frontoparietal (FP) networks and reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, the functional connectivity changes mediate the impact of white matter alterations on cognitive decline in the hypertensive group. Our findings provide a better understanding of the mechanism of cognitive decline in hypertension and highlight the importance of brain protection in hypertension.",Aged;Brain Mapping;Cognition Disorders/ etiology/ pathology/rehabilitation;Diffusion Tensor Imaging;Female;Frontal Lobe/ pathology;Humans;Hypertension/ complications;Male;Middle Aged;Negotiating;Neural Pathways/pathology;Neuropsychological Tests;Parietal Lobe/ pathology;Principal Component Analysis;Rest;Statistics as Topic;White Matter/ pathology,"Li, X.;Liang, Y.;Chen, Y.;Zhang, J.;Wei, D.;Chen, K.;Shu, N.;Reiman, E. M.;Zhang, Z.",2015,Jul 8,10.1523/jneurosci.5113-14.2015,0,
2943,The association between biomarkers in cerebrospinal fluid and structural changes in the brain in patients with Alzheimer's disease,"BACKGROUND: Biochemical changes in the cerebrospinal fluid (CSF) could reflect pathophysiological processes in Alzheimer's disease (AD). However, it is still not clear how these processes correlate with grey matter (GM) volume and microstructural changes in the brain. OBJECTIVE: To assess the relationship between CSF biomarkers and structural brain changes in AD. DESIGN AND SETTING: Cross-sectional study in a memory clinic-based sample. SUBJECTS: A total of 78 subjects were included in the study: 22 with subjective cognitive impairment (SCI), 35 with mild cognitive impairment (MCI) and 21 with AD. MAIN OUTCOME MEASURES: Voxel-wise correlations between CSF biomarkers, including beta-amyloid42 (Abeta42), tau phosphorylated at position threonine 181 and total tau protein, and GM volume, self-diffusion fractional anisotropy (FA) and mean diffusivity (MD) maps using voxel-based morphometry and tract-based spatial statistical analyses. FA and MD maps were obtained using diffusion tensor imaging. RESULTS: In the whole sample (patients with SCI, MCI and AD), there was positive correlation between GM volume and Abeta42 concentration, and negative correlation with total tau protein. Higher FA was only related to higher concentration of Abeta42. MD showed significant negative correlation with Abeta42 and positive correlation with T-tau levels. The majority of brain regions with significant correlation with CSF biomarkers overlapped with the default mode network and extended to the adjacent white matter. CONCLUSIONS: Early AD pathological changes can be detected with voxel-based morphometric analysis and diffusion tensor imaging measurements. Furthermore, there was an association between CSF AD biomarkers and structural brain changes in areas related to the default mode network.","Aged;Alzheimer Disease/ cerebrospinal fluid/ pathology/physiopathology;Amyloid beta-Peptides/ cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Brain/metabolism/ pathology/physiopathology;Cross-Sectional Studies;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/cerebrospinal fluid/pathology;Neuropsychological Tests;Peptide Fragments/cerebrospinal fluid;Phosphorylation;Predictive Value of Tests;Sensitivity and Specificity;Severity of Illness Index;Threonine/metabolism;tau Proteins/ cerebrospinal fluid","Li, X.;Li, T. Q.;Andreasen, N.;Wiberg, M. K.;Westman, E.;Wahlund, L. O.",2014,Apr,10.1111/joim.12164,0,
2944,Novel mutation of HTRA1 gene causes cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy: one case,"Objective: To report a novel HTRA1 gene mutation caused cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) with migraine, urinary retention and constipation. Methods: The patient was a 34-year-old woman who suffered from myalgia with cramp for 16 years, lumbago for 5 years, migraine and mild alopecia for 3 years, right hemiparesis for 5 months, and urinary retention and constipation for 1 month. Vertebral MRI showed degeneration of vertebral bodies with disc herniations. Brain MRI revealed diffuse white matter lesions and lacunar infarcts. Sural nerve and skin biopsies were performed in the patient. HTRA1 gene analysis was performed in patient, her parents and 2 brothers, and Notch3 gene analysis in the patient. Results: The sural biopsy demonstrated discontinuous of elastica internal with thickness of intima of arterioles. The capillary basement membranes were thickness with mini granular changes. A homozygous T to A transition at position 524(c. 524T > A) was found in HTRA1 gene. The heterozygous c. 524T > A mutation appeared in the parents and 2 brothers, but not in the controls. Notch3 mutations were not found in the patient. Conclusion: CARASIL caused by novel homozygous c. 524T > A mutation of HTRA1 gene can present with migraine, urinary retention and constipation. Copyright © 2012 by the Chinese Medical Association.",biological marker;HTRA1 protein;Notch3 receptor;unclassified drug;adult;alopecia;arterial wall thickness;article;autosomal dominant disorder;case report;cerebral autosomal recessive arteriopathy with subcortical infarct and leukoencephalopathy;constipation;controlled study;female;gene mutation;genetic analysis;hemiparesis;human;intervertebral disk hernia;lacunar stroke;low back pain;migraine;muscle cramp;myalgia;nerve biopsy;neuroimaging;nuclear magnetic resonance imaging;skin biopsy;urine retention;vertebra body;white matter lesion,"Li, W. R.;Zhao, D. H.;Wang, Z. X.;Hong, D. J.;Zhang, W.;Yuan, Y.",2012,,,0,
2945,Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure,"BACKGROUND AND OBJECTIVE: Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with white matter (WM) disruptions of the fronto-limbic and interhemispheric tracts implicated in mood regulation and episodic memory functions. This work investigates the extent of these WM abnormalities in patients LLD and aMCI when these diseases occur alone and when they coexist. MATERIALS AND METHODS: Eighty-four subjects separated into cognitively normal (n=33), LLD (n=20), aMCI (n=18), and comorbid aMCI and LLD (n=13) completed Diffusion Tensor Imaging (DTI) scans. Tract-based spatial statistics was employed to skeletonize multiple DTI indices of the cingulum, corpus callosum, fornix and uncinate fasciculus. Analysis of covariance and post-hoc tests compared group differences. Multiple linear regressions were performed between DTI and behavioral measures for the whole sample and within individual patient groups. RESULTS: Divergent microstructural disruptions were identified in LLD- and aMCI-only groups, whereas the comorbid group showed widespread abnormalities especially in the hippocampal cingulum and fornix tracts. The LLD groups also showed significant disruptions in the uncinate fasciculus and corpus callosal tracts. Higher depressive symptom and lower episodic memory scores were associated with increased diffusivity measures in the fornix and hippocampal cingulum across all subjects. CONCLUSIONS: Widespread WM microstructural disruptions are present when LLD and aMCI are comorbid -especially in the medial temporal lobe tracts. These WM disruptions may be a marker of disease severity. Also, multiple DTI parameters should be used when evaluating the WM fiber integrity in LLD and aMCI.","Aged;Aged, 80 and over;Analysis of Variance;Anisotropy;Brain/pathology;Depression/complications/etiology/pathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/ complications/diagnosis;Male;Middle Aged;Mild Cognitive Impairment/complications/etiology/pathology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Psychiatric Status Rating Scales","Li, W.;Muftuler, L. T.;Chen, G.;Ward, B. D.;Budde, M. D.;Jones, J. L.;Franczak, M. B.;Antuono, P. G.;Li, S. J.;Goveas, J. S.",2014,Mar 15,10.1016/j.jns.2013.12.016,0,
2946,Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status,"Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection. © 2013 Journal of NeuroVirology, Inc.",efavirenz plus emtricitabine plus tenofovir disoproxil;gelatinase A;gelatinase B;interstitial collagenase;matrilysin;stromelysin 2;virus RNA;acquired immune deficiency syndrome;adult;analyzer;article;brain function;cerebrospinal fluid analysis;controlled study;diffusion tensor imaging;disease course;enzyme assay;female;HIV associated dementia;human;Human immunodeficiency virus infection;in vivo study;major clinical study;male;medical technology;neuroAIDS;neuroimaging;neuropsychological test;North American Adult Reading Test;nuclear magnetic resonance imaging;priority journal;reading;viremia;virus load;atripla;Bio-Plex Manager 6.0 Software;LABScan 100 analyzer;MILLIPLEX MAP Human MMP Panel 2,"Li, S.;Wu, Y.;Keating, S. M.;Du, H.;Sammet, C. L.;Zadikoff, C.;Mahadevia, R.;Epstein, L. G.;Ragin, A. B.",2013,,,0,
2947,Regional white matter decreases in Alzheimer's disease using optimized voxel-based morphometry,"BACKGROUND: Most studies that attempt to clarify structural abnormalities related to functional disconnection in patients with Alzheimer's disease (AD) have focused on exploring pathological changes in cortical gray matter. However, white matter fibers connecting these cerebral areas may also be abnormal. PURPOSE: To investigate the regional changes of white matter volume in patients with AD compared to healthy subjects. MATERIAL AND METHODS: White matter volume changes in whole-brain magnetic resonance images acquired from 19 patients with AD and 20 healthy subjects (control group) were observed using the optimized voxel-based morphometry (VBM) method. In addition, the corpus callosum (CC) of AD patients and the control group was investigated further by outlining manually the boundary of the CC on a midsagittal slice. Each area of the CC was then corrected by dividing each subject's intracranial area in the midsagittal plane. RESULTS: Compared with the control group, AD patients showed significantly reduced white matter volumes in the posterior part of the CC and the temporal lobe in the left and right hemispheres. Moreover, the voxel showing peak statistical difference in the posterior of the CC was left sided. The five subdivisions of the CC were also significantly smaller among the AD patients relative to the control group. CONCLUSION: Our findings suggest that these abnormalities in white matter regions may contribute to the functional disconnections in AD.","Aged;Alzheimer Disease/ diagnosis;Brain Mapping/methods;Corpus Callosum/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Magnetic Resonance Spectroscopy/methods;Male;Reference Values;Temporal Lobe/ pathology","Li, S.;Pu, F.;Shi, F.;Xie, S.;Wang, Y.;Jiang, T.",2008,Feb,,0,2948
2948,Regional white matter decreases in Alzheimer's disease using optimized voxel-based morphometry,"BACKGROUND: Most studies that attempt to clarify structural abnormalities related to functional disconnection in patients with Alzheimer's disease (AD) have focused on exploring pathological changes in cortical gray matter. However, white matter fibers connecting these cerebral areas may also be abnormal. PURPOSE: To investigate the regional changes of white matter volume in patients with AD compared to healthy subjects. MATERIAL AND METHODS: White matter volume changes in whole-brain magnetic resonance images acquired from 19 patients with AD and 20 healthy subjects (control group) were observed using the optimized voxel-based morphometry (VBM) method. In addition, the corpus callosum (CC) of AD patients and the control group was investigated further by outlining manually the boundary of the CC on a midsagittal slice. Each area of the CC was then corrected by dividing each subject's intracranial area in the midsagittal plane. RESULTS: Compared with the control group, AD patients showed significantly reduced white matter volumes in the posterior part of the CC and the temporal lobe in the left and right hemispheres. Moreover, the voxel showing peak statistical difference in the posterior of the CC was left sided. The five subdivisions of the CC were also significantly smaller among the AD patients relative to the control group. CONCLUSION: Our findings suggest that these abnormalities in white matter regions may contribute to the functional disconnections in AD.",,"Li, S.;Pu, F.;Shi, F.;Xie, S.;Wang, Y.;Jiang, T.",1987,Feb,,0,
2949,Characteristics and risk factors analysis of cognitive decline in elderly patients with cerebral infarction,"Objective: To investigate the characteristics and risk factors for cognitive decline in elderly patients with cerebral infarction. Methods: A cross-sectional study was performed to investigate the population of Jiangan Town, Rugao,Jiangsu Province from November 13,2014 to December 21,2014. The samples from the Rugao longitudinal study of aging included 1 788 individuals from 31 villages aged from 70 to 84 years. They were all Han nationality including 830 males and 958 females. History of cerebral infarction was identified according to the neurological diagnosis confirmed by the secondary hospital and above or brain CT. The modified Kyohko Hasegawa dementia scale was used to evaluate the cognitive function. Five dimensions (orientation,memory,near memory,computing power,and common sense) of this population were assessed. The total score <21.5 was non-cognitive impairment and ≥21.5 was cognitive impairment. Multivariate logistic regression was used to analyze the risk factors for cognitive decline in elderly patients with cerebral infarction. Results: (1) In the 1 788 subjects, 133 had cerebral infarction (7.4%), and 1 655 did not have cerebral infarction. The proportion of hypertension in patients with cerebral infarction was higher than that without cerebral infarction (63. 9% [n = 85] vs. 41.7% [n = 690]). The high-density lipoprotein cholesterol level was lower than that of the non-cerebral infarction group (1.40 ±0.29 mmol/L vs. 1. 47 ± 0. 33 mmol/L). There was statistically significant difference (all P<0.05). (2) The patients with cerebral infarction were partially impaired in orientation and computational power,and the overall cognitive function score was 20 ±7, which was significantly lower than patients with non-cerebral infarction (21 ± 6). The difference between the two groups was statistically significant (P < 0.05). (3) In 133 patients with cerebral infarction, 76 had cognitive impairment, the incidence was 57. 1%,and 59 of them were women. The average value of serum creatinine in patients with cognitive impairment was 59 ± 15 μ.mol/L, which was significantly lower than those with non-cognitive impairment (66 ± 14 μmol/L). There was significant difference (P<0.05). (4) Multivariate logistic regression analysis showed that the education level below primary school (OR,2. 86,95% CI 2. 19-3. 72) and female (OR, 1. 85,95% CI 1.50-2.28) were the independent risk factors for cognitive decline in elderly patients with cerebral infarction. High serum creatinine concentration (OR,0. 96,95 % CI 0. 95-0.97) was a protective factor for it. Conclusion: The cognitive function of the elderly was decreased after cerebral infarction, especially in the aspect of orientation and calculation. The education level below primary school and women were the independent risk factors for cognitive impairment, and high serum creatinine concentration had a certain protective effect.",creatinine;high density lipoprotein cholesterol;aged;aging;article;brain function;brain infarction;cholesterol blood level;cognition;cognitive defect;common sense;computer assisted tomography;computing power;controlled study;creatinine blood level;cross-sectional study;dementia assessment;education;female;human;incidence;longevity;longitudinal study;major clinical study;male;memory;modified Kyohko Hasegawa dementia scale;orientation;primary school;risk assessment;risk factor;secondary care center;sex difference,"Li, S.;Liu, Q.;Li, Y.;Hu, Z.;Jiang, X.;Wang, X.;Shi, J.;Hu, W.",2017,,10.3969/j.issn.1672-5921.2017.05.001,0,
2950,Decreased serum bilirubin is associated with silent cerebral infarction,"OBJECTIVE: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease, and dementia. Total bilirubin (TB) levels were demonstrated to be decreased in carotid intima-media thickness, cardiovascular disease, stroke, and peripheral arterial disease. However, little information is available concerning the correlation between TB and SCI. APPROACH AND RESULTS: A cross-sectional study was conducted to evaluate the association between TB and SCI in 2865 subjects (1831 men and 1034 women) undergoing medical checkup. The participants with SCI had lower TB levels than those without SCI. The subjects with a low TB had a higher prevalence of SCI. Moreover, partial correlation showed that TB levels were tightly correlated with brachial-ankle pulse wave velocity after adjusting for confounding covariates (r=-0.149; P<0.001). Multivariate logistic regression analysis revealed that higher TB was associated with a lower risk of SCI (odds ratio, 0.925; 95% confidence interval, 0.897-0.954; P<0.001). CONCLUSIONS: TB is a novel biochemical indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of TB may be useful to assess the risk of SCI.",Adult;Aged;Ankle Brachial Index;Asymptomatic Diseases;Bilirubin/*blood;Biomarkers/blood;Cerebral Infarction/*blood/diagnosis/epidemiology;Chi-Square Distribution;China/epidemiology;Cross-Sectional Studies;Down-Regulation;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Odds Ratio;Prevalence;Pulse Wave Analysis;Risk Factors;atherosclerosis;bilirubin;cerebral infarction,"Li, R. Y.;Cao, Z. G.;Zhang, J. R.;Li, Y.;Wang, R. T.",2014,Apr,10.1161/atvbaha.113.303003,0,
2951,Increased whole blood viscosity is associated with silent cerebral infarction,"BACKGROUND: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease and dementia. Increased viscosity is associated with aging, obesity, carotid intima-media thickness, metabolic syndrome, hypertension, diabetes, ischemic heart disease, and stroke. AIMS: The purpose of the study was to assess the hemorheological parameters levels in SCI patients. METHODS: A cross-sectional study was conducted to evaluate the association between hemorheological parameters and SCI in 1487 subjects (868 men and 619 women) undergoing medical check-up. RESULTS: The participants with SCI had higher whole blood viscosity (WBV) levels at low shear rate than those without SCI (10.34 +/- 1.77 mPa.s vs. 8.98 +/- 0.88 mPa.s; P < 0.001). Moreover, the subjects with a high WBV had a higher prevalence of SCI. Logistic regression analysis revealed that a significant association of WBV levels with the risk of SCI after adjustment for confounding factors (OR: 2.025; 95% CI: 1.750-2.343; P < 0.001). CONCLUSIONS: Whole blood viscosity at low shear rate is a novel indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of whole blood viscosity may be helpful to assess the risk of stroke.",Adult;*Blood Viscosity;Cerebral Infarction/*blood/diagnosis;Cross-Sectional Studies;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Silent cerebral infarction;atherosclerosis;risk factors;whole blood viscosity,"Li, R. Y.;Cao, Z. G.;Li, Y.;Wang, R. T.",2015,,10.3233/ch-131760,0,
2952,White matter damage and effects of nadir CD4(+) count on patients with asymptomatic HIV associated dementia complexe-A DTI study,"Objective: In this study we investigate the quantitative diffusion tensor imaging (DTI) changes of normal-appearing white matter (NAWM) in patients with stage 0 asymptomatic HIV-1 associated dementia complex (HAD), and clinical factors contributing to it. Materials and methods: Conventional magnetic resonance imaging (cMRI) and DTI were performed in 40 patients with stage 0 asymptomatic HAD (24 patients with CD4(+) counts <200 cells/mm(3), 16 patients with CD4(+) counts >200 cells/mm(3) and 40 healthy volunteers with similar gender/age. Quantitative DTI values-fractional anisotropy (FA)/apparent diffusion coefficient (ADC) of normal-appearing white matter (NAWM) in frontal, parietal, temporal, occipital lobes, genu, splenium and body of the corpus callosum (CC), corona radiate (CR), centrum semiovale (CSO), and anterior and posterior limbs of the internal capsule were measured and analyzed. Results: The mean FA values were much lower and the mean ADC values were significantly higher in the CC body and CSO in stage 0 HAD patients than in the controls (P < 0.05). In comparison with controls, the patients with stage 0 asymptomatic HAD had significantly higher ADC values (P < 0.05) for frontal, parietal, occipital lobes, CC body, CR and CSO, FA values of the corresponding regions were reduced, but the differences were not statistically significant (all P > 0.05). FA values were reduced and ADC values were higher in other white matter regions, but did not show any significant difference between the two groups (P > 0.05). Significantly higher ADC values in the frontal and CR in patients with CD4(+) counts <200 cells/mm(3) compared with the patients with CD4(+) counts >200 cells/mm(3) and the controls. Conclusions: Quantitative DTI could help better evaluation of white matter abnormalities in stage 0 asymptomatic HAD, this may be helpful for early and accurate prevention and treatment of HAD, and for preventing or reversing cognitive decline. The quantitative DTI value changes indicated that in early phase of HAD there is a preferential occult injury of frontal lobe and CSO. Nadir CD4 (+) count may be a great risk for HAD.",,"Li, R.;Mi, H.;Zhao, J.;Yuan, D.;Ding, J.;Li, H.",2014,2014,,0,
2953,Classification of Cognitive Level of Patients with Leukoaraiosis on the Basis of Linear and Non-Linear Functional Connectivity,"Leukoaraiosis (LA) describes diffuse white matter abnormalities apparent in computed tomography (CT) or magnetic resonance (MR) brain scans. Patients with LA generally show varying degrees of cognitive impairment, which can be classified as cognitively normal (CN), mild cognitive impairment (MCI), and dementia. However, a consistent relationship between the degree of LA and the level of cognitive impairment has not yet been established. We used functional magnetic resonance imaging (fMRI) to explore possible neuroimaging biomarkers for classification of cognitive level in LA. Functional connectivity (FC) between brain regions was calculated using Pearson's correlation coefficient (PCC), maximal information coefficient (MIC), and extended maximal information coefficient (eMIC). Next, FCs with high discriminative power for different cognitive levels in LA were used as features for classification based on support vector machine. CN and MCI were classified with accuracies of 75.0, 61.9, and 91.1% based on features from PCC, MIC, and eMIC, respectively. MCI and dementia were classified with accuracies of 80.1, 86.2, and 87.4% based on features from PCC, MIC, and eMIC, respectively. CN and dementia were classified with accuracies of 80.1, 89.9, and 94.4% based on features from PCC, MIC, and eMIC, respectively. Our results suggest that features extracted from fMRI were efficient for classification of cognitive impairment level in LA, especially, when features were based on a non-linear method (eMIC).",cognitive level classification;eMIC;fMRI;functional connectivity;leukoaraiosis,"Li, R.;Lai, Y.;Zhang, Y.;Yao, L.;Wu, X.",2017,,,0,
2954,Discriminative analysis of multivariate features from structural MRI and diffusion tensor images,"Imaging markers derived from magnetic resonance images, together with machine learning techniques allow for the recognition of unique anatomical patterns and further differentiating Alzheimer's disease (AD) from normal states. T1-based imaging markers, especially volumetric patterns have demonstrated their discriminative potential, however, rely on the tissue abnormalities of gray matter alone. White matter abnormalities and their contribution to AD discrimination have been studied by measuring voxel-based intensities in diffusion tensor images (DTI); however, no systematic study has been done on the discriminative power of either region-of-interest (ROI)-based features from DTI or the combined features extracted from both T1 images and DTI. ROI-based analysis could potentially reduce the feature dimensionality of DTI indices, usually from more than 10e. +. 5, to 10-150 which is almost equal to the order of magnitude with respect to volumetric features from T1. Therefore it allows for straight forward combination of intensity based landmarks of DTI indices and volumetric features of T1. In the present study, the feasibility of tract-based features related to Alzheimer's disease was first evaluated by measuring its discriminative capability using support vector machine on fractional anisotropy (FA) maps collected from 21 subjects with Alzheimer's disease and 15 normal controls. Then the performance of the tract-based FA. +. gray matter volumes-combined feature was evaluated by cross-validation. The combined feature yielded good classification result with 94.3% accuracy, 95.0% sensitivity, 93.3% specificity, and 0.96 area under the receiver operating characteristic curve. The tract-based FA and the tract-based FA. +. gray matter volumes-combined features are certified their feasibilities for the recognition of anatomical features and may serve to complement classification methods based on other imaging markers. © 2014 Elsevier Inc.",,"Li, M.;Qin, Y.;Gao, F.;Zhu, W.;He, X.",2014,October,,0,
2955,Clinical predictors of cognitive decline in patients with mild cognitive impairment: the Chongqing aging study,"Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefore, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus (p = 0.004), baseline WMC severity (p < 0.001), baseline carotid stenosis (p < 0.001), and WMC severity change (p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia.","Aged;Aged, 80 and over;Aging;Brain/ pathology/radiography;Cerebrovascular Disorders/complications/epidemiology;China/epidemiology;Cognition Disorders/ diagnosis/ epidemiology/etiology;Cohort Studies;Dementia/diagnosis;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Proportional Hazards Models;Psychiatric Status Rating Scales;Risk Factors;Tomography Scanners, X-Ray Computed","Li, L.;Wang, Y.;Yan, J.;Chen, Y.;Zhou, R.;Yi, X.;Shi, Q.;Zhou, H.",2012,Jul,10.1007/s00415-011-6342-0,0,
2956,Parametric mapping of scaled fitting error in dynamic susceptibility contrast enhanced MR perfusion imaging,"The purpose of this study was to examine the benefits of routine generation of a parametric image of scaled curve fitting errors in the analysis of dynamic susceptibility contrast enhanced MR perfusion imaging. We describe the scaled fitting error (SFE), which reflects the magnitude of potential errors in the estimation of perfusion parameters from dynamic susceptibility contrast enhanced studies. The SFE is the root-mean-square error between the observed values in the time course of change of effective transverse relaxation rate (ΔR2*(t)) in tissue and the theoretical values derived by Γ variate curve fitting, scaled with a simple function related to the area under the fitted Γ variate curve. The SFE was tested using Monte Carlo simulation and by observations in normal volunteers and patients. This demonstrated that the SFE was linearly related to uncertainties in calculation of the values of relative cerebral blood volume (rCBV) and relative meant transit time (rMTT). High spatial resolution SFE maps were obtained in all volunteers and patients. In normal brain, SFE was consistently higher in white matter than in grey matter. In 54/85 patients with neurodegenerative or vascular brain disease, SFE maps showed focal areas with high values owing to poor signal to noise ratio in ΔR2*(t). Increased SFE was also found in 11/54 brain tumours owing to loss of conformance of ΔR2*(t) to the Γ variate function. SFE mapping is simple to implement and the computational overhead is negligible. It is concluded that parametric maps of SFE allow visual and quantitative comparison of fitting errors with the theoretical Γ variate model between anatomical regions and provide a quality control device to rapidly assess the reliability of the associated rCBV and rMTT estimations.",,"Li, K. L.;Zhu, X. P.;Jackson, A.",2000,2000,,0,
2957,Study of intracerebral focus changes on CADASIL by using MR imaging,"OBJECTIVE: To investigate dynamic changes of intracerebral focus on cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: Using the modified Scheltens scale, the magnetic resonance (MR) changes of lesion distribution, size and shape in 7 patients from a CADASIL family were retrospectively analyzed during 3 years observed. RESULTS: In 6 of 7 patients, the number and volume of lesion areas in the white matter were increased (parietal lobe, n = 6; temporal lobe, n = 5; frontal lobe, n = 3; occipital lobe, n = 2) and some areas even became confluent as a mass or chain. New lacunar infarcts (n = 1 - 5) appeared in 5 patients and the arcuate fiber were involved in 1 patients. Slight enlargement could be seen in lateral ventricle (n = 1) or lateral ventricle with third ventricle (n = 1). CONCLUSION: MR imaging can help us to reveal dynamic changes of brain lesions and prognosis in patients with CADASIL.",Adult;Brain/pathology;Brain Infarction/pathology;CADASIL/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Prognosis;Retrospective Studies,"Li, J. C.;Jin, D. X.;Yang, Y. J.;Chen, X. Y.;Li, J. L.;Wang, M. H.;Wu, E. F.",2007,Jul 10,,0,
2958,A Functional Varying-Coefficient Single-Index Model for Functional Response Data,"Motivated by the analysis of imaging data, we propose a novel functional varying-coefficient single index model (FVCSIM) to carry out the regression analysis of functional response data on a set of covariates of interest. FVCSIM represents a new extension of varying-coefficient single index models for scalar responses collected from cross-sectional and longitudinal studies. An efficient estimation procedure is developed to iteratively estimate varying coefficient functions, link functions, index parameter vectors, and the covariance function of individual functions. We systematically examine the asymptotic properties of all estimators including the weak convergence of the estimated varying coefficient functions, the asymptotic distribution of the estimated index parameter vectors, and the uniform convergence rate of the estimated covariance function and their spectrum. Simulation studies are carried out to assess the finite-sample performance of the proposed procedure. We apply FVCSIM to investigating the development of white matter diffusivities along the corpus callosum skeleton obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) study.",Functional data analysis;Image data analysis;Single index model;Varying-coefficient model,"Li, J.;Huang, C.;Zhu, H.",2017,,,0,
2959,Glucose metabolism measured by positron emission tomography is reduced in patients with white matter presumably ischemic lesions,"BACKGROUND: The severity and progression of white matter ischemic lesion (WMIL) are closely linked to vascular dementia. The function of neural tissue is closely linked to glucose consumption as the most important energy-supplying metabolic process. At present, [18]fluorine-fluorodeoxy glucose ([18]FDG) positron emission tomography (PET) can provide regional and 3-dimensional quantification of glucose metabolism in the human brain. Although MMSE and MoCA are commonly used screens in cognitive impairment, no research team has yet validated their performance in WMIL. The purpose of our study was to compare MMSE and MoCA in screening for cognitive impairment and to explore the correlations between CMRglu values and executive function. MATERIAL AND METHODS: All the participants underwent comprehensive clinical, MoCA, MMSE, MRI, and PET examinations. Patients in the WMIL group were subdivided into 3 severity subgroups according to the Fazekas scale. RESULTS: The MoCA scores were lower in the WMIL group. Our research indicates that MoCA is a more sensitive screening tool than the commonly used MMSE in detecting cognitive impairment in patients with WMIL. CMRglu values of gray matter were decreased in the WMIL group. Reductions of CMRglu in parietal lobe, frontal lobe, and white matter centrum semiovale were observed to different degrees in the WMIL groups according to the modified Fazekas scale. A significant negative correlation was found between executive function and CMRglu in the frontal lobe. CONCLUSIONS: MoCA appears to be a more sensitive screening tool than the commonly used MMSE in detecting cognitive impairment in patients with WMIL. CMRglu can potentially be used as a biomarker for predicting the severity of WMIL.",Aged;Brain Ischemia/*metabolism/*radionuclide imaging;Case-Control Studies;Female;Frontal Lobe/metabolism/radionuclide imaging;Glucose/*metabolism;Humans;Male;Neuropsychological Tests;*Positron-Emission Tomography;Risk Factors;Temporal Lobe/metabolism/radionuclide imaging;White Matter/*metabolism/pathology/*radionuclide imaging,"Li, J.;Hu, W.",2014,,10.12659/msm.892137,0,
2960,Different patterns of white matter disruption among amnestic mild cognitive impairment subtypes: relationship with neuropsychological performance,"Amnestic mild cognitive impairment (aMCI) is recognized as the prodromal phase of Alzheimer's disease (AD). Evidence showed that patients with multiple-domain (MD) aMCI were at higher risk of converting to dementia and exhibited more severe gray matter atrophy than single-domain (SD) aMCI. The investigation of the microstructural abnormalities of white matter (WM) among different subtypes of aMCI and their relations with cognitive performances can help to understand the variations among aMCI subtypes and to construct potential imaging based biomarkers to monitor the progression of aMCI. Diffusion-weighted MRI data were acquired from 40 patients with aMCI (aMCI-SD: n = 19; aMCI-MD: n = 21) and 37 healthy controls (HC). Voxel-wise and atlas-based analyses of whole-brain WM were performed among three groups. The correlations between the altered diffusion metrics of the WM tracts and the neuropsychological scores in each subtype of aMCI were assessed. The aMCI-MD patients showed disrupted integrity in multiple WM tracts across the whole-brain when compared with HCs or with aMCI-SD. In contrast, only few WM regions with diffusion changes were found in aMCI-SD as compared to HCs and with less significance. For neuropsychological correlations, only aMCI-MD patients exhibited significant associations between disrupted WM connectivity (in the body of the corpus callosum and the right anterior internal capsules) and cognitive impairments (MMSE and Digit Symb-Coding scores), whereas no such correlations were found in aMCI-SD. These findings indicate that the degeneration extensively exists in WM tracts in aMCI-MD that precedes the development of AD, whereas underlying WM pathology in aMCI-SD is imperceptible. The results are consistent with the view that aMCI is not a uniform disease entity and presents heterogeneity in the clinical progression.","Aged;Aged, 80 and over;Analysis of Variance;Brain/ pathology;Brain Mapping;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Li, H.;Liang, Y.;Chen, K.;Li, X.;Shu, N.;Zhang, Z.;Wang, Y.",2013,,10.3233/jad-122023,0,
2961,[Clinical and CT analysis of multiple cerebral infarction (with a report of 261 cases)],,"Adolescent;Adult;Aged;Brain/*radiography;*Cerebral Infarction/pathology/radiography;*Dementia/pathology;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Li, G. Z.",1988,Feb,,0,
2962,Cerebral watershed infarcts,"OBJECTIVE: To investigate the clinical types and characteristics of cerebral watershed infarcts (CWI). METHODS: Analysis of the clinical data and imaging characteristics of 192 cases with CWI confirmed by CT scan or MRI. RESULTS: In 69 cases (35.9%), CWI appeared as wedge-shaped areas on CT scan or MRI, the infarcts located at marginal zones between the anterior and middle cerebral arteries and were usually associated clinically with hemiparesis, transcortical motor aphasia and dementia. In 74 cases (38.5%) the infarcts also appeared as wedge-shaped areas on CT scan and MRI, but located at marginal zones between the middle and posterior cerebral arteries, the patients mainly showed mild hemiparesis and apathy. In 49 cases (25.5%), the long-line or triangle-shaped infarct areas usually located at marginal zones between the superficial and deep territory of the middle cerebral arteries in the basal ganglia and posterolateral angulus frontalis. CONCLUSION: The presentation of CWI is complicated, and the diagnosis of that mainly depends on imaging studies such as CT scan and MRI.","Adult;Aged;Aged, 80 and over;Cerebral Infarction/ diagnosis/pathology/physiopathology;Cerebrovascular Circulation;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Li, G.;Yang, X.;Cai, J.;Yao, Q.",2001,Apr,,0,
2963,Diffusion tensor imaging of patients with behavioral variant frontotemporal dementia: A controlled study,"Background: This study aimed to investigate the clinically important early symptoms of behavioral variant frontotemporal dementia (bvFTD) and the characteristics of bvFTD in structural imaging and to explore the value of diffusion tensor magnetic resonance imaging (MRI-DTI) in the early diagnosis of bvFTD. Material and Methods: Siemens 3T Verio MRI with echoplanar imaging (EPI) was employed in 8 patients with suspected bvFTD diagnosed according to the FTDC diagnostic consensus, 8 matched Alzheimer’s disease (AD) patients and 8 healthy controls, and 3DT1 and DWI images were collected. Results: DTI showed the bilateral thalamic radiation, cingulate gyrus and hippocampus had significantly reduced FA (P<0.001). After FEW correction, FA in these regions was compa­rable between bvFTD patients and AD patients. The MD of the anterior frontal lobe and temporal lobe increased significantly in bvFTD patients, suggesting more severe white matter damage. Analysis of lateralization effect of FA showed lateralization distribution in the left thalamic radiation, inferior longitudinal fasciculus and cingulate gyrus in bvFTD patients as compared to healthy controls. Conclusion: MRI-DTI shows evident white matter lesions in bvFTD patients, and the injury to white matter at left thalamic radiation, left cingulate gyrus, forceps minor, left fasciculus occipitofrontalis inferior, right inferior longitudinal fasciculus and left uncinate fasciculus deteriorates. Moreover, the asymmetrical damage to the left thalamic radiation, left inferior longitudinal fasciculus and left cingulated is helpful for the early differential diagnosis.",,"Li, G.;Tang, Y.;Yue, L.;Wang, J.;Zhang, J.;Xiao, S.;Li, H.",2016,29,,0,
2964,Quantitative investigation of patients with vascular dementia by CT and transcranial Dopple,"Aim: To investigate the changes of cranial CT and transcranial Dopple in patients with vascular dementia (VD) and to master the clinical features of VD. Methods: Thirty VD patients, 20 males and 10 females with an average age of 68.2 years, and 30 cerebral infarction patients without obvious cognitive deficits, 20 males and 10 females with the average age of 67.4 years, who came from the same hospital in the same period, were enrolled in the study. CT scan and transcranial Dopple were conducted to determine focal cerebral lesions, cerebral atrophy and cerebral blood fluid respectively. Results: 1) The patients with multiple infarctions were more frequently seen in VD patients than in cerebral infarction patients without obvious cognitive deficits. 2) The focal volume of cerebral infarction in VD patients was (26.3 ± 37.8) cm3, significantly higher than that of cerebral infarction patients [(7.8 ± 15.5) cm3, t = 2.49, P = 0.016]. The widths of third brain ventricle and Ha were (0.84 ± 0.14) cm and (5.76 ± 0.71) cm respectively in VD group, significantly higher than in cerebral infarction group [(0.62 ± 0.15), (5.19 ± 0.63) cm, t = 3.75, P = 0.001; 3.35, P = 0.002]. 3 Resistent indexes of the patients with VD were bigger than those of the patients with cerebral infarction (t = 2.07 - 3.09, P < 0.05 - 0.01). Conclusion: Vascular dementia patients have obvious changes in CT and transcranial Doppler, commonly with the decline in vascular elasticity.",aged;article;brain atrophy;brain injury;brain ischemia;brain ventricle;clinical article;clinical feature;cognitive defect;computer assisted tomography;controlled study;Doppler echography;elasticity;female;human;intermethod comparison;male;multiinfarct dementia;quantitative analysis,"Li, F. P.;Zheng, J.",2003,,,0,
2965,Antiphospholipid syndrome presenting as progressive neuropsychiatric disorders: two case reports,"The antiphospholipid syndrome (APS) is a rare form of autoimmune coagulopathy. In this syndrome, the most common neurologic abnormality is transient ischemic attack. This can be easily overlooked if a patient presents with progressive neuropsychiatric disorders, such as depression or dementia. We report two cases of young women, aged 35 and 22 years, presenting with progressive depression and mental decline over a certain period. The neuropsychological diagnoses of the two patients were, respectively, dementia with disinhibition and borderline dementia with depression. Brain magnetic resonance imaging showed multiple old infarcts with encephalomalacia in the former case, and only one cortical hemorrhagic infarction, over the right temporoparietal lobe, observed in the latter case. The outcomes of the two cases were also very different. Progressive neuropsychiatric disorders are increasingly observed in the young; therefore, APS and other autoimmune diseases should be considered during the differential diagnosis. Brain imaging examinations may prevent a delay in the detection of a structural lesion and facilitate the early intervention with good prognosis. Careful investigations by experts from different disciplines are always encouraged in complicated cases.",,"Li, C. H.;Chou, M. C.;Liu, C. K.;Lai, C. L.",2013,,10.2147/ndt.s44140,0,
2966,Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer's disease and normal aging,"We studied normotensive and nondiabetic subjects, free of cardiac disorders, to determine whether Alzheimer's disease is a possible factor of magnetic resonance imaging (MRI) white matter or periventricular hyperintensities, and to investigate relationships between computed tomographic scan and MRI changes. We failed to reveal (1) any difference in the severity of MRI white matter and periventricular hyperintensities between patients and controls, (2) any correlation of MRI white matter and periventricular hyperintensities with either ages or Mini-Mental State Examination scores. We found (1) a poor interobserver agreement, and (2) a correlation between computed tomographic scan and MRI white matter changes but not between computed tomographic and MRI periventricular changes. We conclude that MRI periventricular and white matter hyperintensities are frequent incidental findings in the elderly and do not significantly differ between patients with Alzheimer's disease and healthy controls.",Aged;Aging/ physiology;Alzheimer Disease/ diagnosis;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Statistics as Topic,"Leys, D.;Soetaert, G.;Petit, H.;Fauquette, A.;Pruvo, J. P.;Steinling, M.",1990,May,,0,
2967,White-matter lesions on CT in Alzheimer patients,,Age Factors;Alzheimer Disease/*radiography;Brain Diseases/*radiography;Cerebrovascular Disorders/complications;Humans,"Leys, D.;Scheltens, P.;Steinling, M.",1991,Sep,,0,
2968,"Could Wallerian degeneration contribute to ""leuko-araiosis"" in subjects free of any vascular disorder?","To determine the possible role of Wallerian degeneration secondary to the grey matter neuronal loss in the pathogenesis of ""leuko-araiosis"", computerised tomography (CT) of the brain was studied in 98 normotensive and non diabetic subjects free of cardiac diseases: 32 with Alzheimer's disease, 36 with Parkinson's disease, eight with progressive supranuclear palsy, and 22 controls. In Alzheimer's disease, leuko-araiosis scores were greater than in control subjects. Leuko-araiosis was more prominent in anterior periventricular areas in Parkinson's disease and progressive supranuclear palsy, and in posterior periventricular areas in Alzheimer's disease. In two patients with Alzheimer's disease and leuko-araiosis, necropsy revealed diffuse white matter pallor, mild fibrillary astrocytosis, and in one patient limited hyaline thickening of small white matter vessels, without any infarction or hypertensive change. Changes were more severe in white matter close to cortical areas with a great density of neurofibrillary tangles. Leuko-araiosis was more severe or more widespread in Alzheimer's disease than in Parkinson's disease, progressive supranuclear palsy and normal ageing. Differences in the location of leuko-araiosis between the four groups might be due to differences in the location of the grey matter disorder and Wallerian degeneration rather than amyloid in Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy and normal ageing. Wallerian degeneration might be another cause of leuko-araiosis in neuro-degenerative disorders beside previously reported extra-cerebral predisposing factors and amyloid angiopathy.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Cerebral Ventricles/*pathology;Female;Humans;Male;Middle Aged;Neurofibrils/ultrastructure;Neurons/pathology;Parkinson Disease/*pathology;Supranuclear Palsy, Progressive/*pathology;*Tomography, X-Ray Computed;Wallerian Degeneration/*physiology","Leys, D.;Pruvo, J. P.;Parent, M.;Vermersch, P.;Soetaert, G.;Steinling, M.;Delacourte, A.;Defossez, A.;Rapoport, A.;Clarisse, J.;et al.",1991,Jan,,0,
2969,White matter changes in stroke patients. Relationship with stroke subtype and outcome,"White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either 'WMC or white matter lesions or leukoencephalopathy or leukoaraiosis' and 'stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)'. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.",,"Leys, D.;Englund, E.;Del Ser, T.;Inzitari, D.;Fazekas, F.;Bornstein, N.;Erkinjuntti, T.;Bowler, J. V.;Pantoni, L.;Parnetti, L.;De Reuck, J.;Ferro, J.;Bogousslavsky, J.",1999,August,,0,
2970,CADASIL: Underdiagnosed in psychiatric patients?,"Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is exclusively related to symptoms of the central nervous system. Retrospectively in up to 15% the initial presentation is psychiatric disturbances. In these cases the diagnosis often is delayed or missed. Method: Two cases of CADASIL diagnosed in a psychiatric hospital are presented. Results: Both patients were admitted to the gerontopsychiatric department (one because of a suicidal attempt and a depressive episode, the other because of cognitive decline and progressive personal neglect). Brain magnetic resonance imaging (MRI) showed severe leukoencephalopathy in the absence of cardiovascular risk factors. In both cases, diagnosis of CADASIL was made by the identification of specific granular osmiophilic material in skin biopsies. Conclusion: Brain MRI should be performed in all cases of late onset of severe psychiatric symptoms. CADASIL should be considered as a possible differential diagnosis whenever a marked leukoencephalopathy is detectable. Diagnosis can be verified by taking a skin biopsy or by specific genetic testing. Copyright © Blackwell Munksgaard 2004.",,"Leyhe, T.;Wiendl, H.;Buchkremer, G.;Wormstall, H.",2005,May,,0,
2971,Neoplastic angioendotheliosis: A case with spontaneous regression and radiographic appearance of cerebral arteritis,"Neoplastic angioendotheliosis (NA) of the CNS is usually characterized by systemic vascular disease and a rapidly fatal course. We report a 52-year-old woman with dementia, spasticity, and sensory deficits developing insidiously over a year. Diagnostic findings included small CT lucencies in the brain and angiographic irregularities of medium-sized arteries (resembling cerebral arteritis). Brain biopsy revealed numerous small infarcts as well as pleomorphic, highly malignant tumor cells within cerebral meningeal vessels. Without treatment, she experienced only slight increase of dementia before death from pneumonia. At autopsy, there was almost complete regression of the intravascular cerebral tumor. The clinical course was unusual for the length of illness and the radiographic picture of cerebral vasculitis. Clinical features often present with NA - such as strokelike events, elevated sedimentation rate, renal impairment, and fever - were notably absent.",angioendotheliosis;brain angiography;brain biopsy;brain infarction;brain vasculitis;case report;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;histology;human,"LeWitt, P. A.;Forno, L. S.;Brant Zawadzki, M.",1983,,,0,
2972,Dementia and leukoencephalopathy due to lymphomatosis cerebri,"Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL). Clinically, the disease typically presents with a rapidly progressive dementia and unsteadiness of gait. Its presentation on cerebral MRI, which is characterised by diffuse leukoencephalopathy without contrast enhancement, often causes diagnostic confusion1 with suspected diagnoses ranging from Binswanger's disease to leukoencephalopathy or encephalomyelitis. Here we report a patient with subacute dementia and diffuse bilateral white matter changes in the cerebral hemispheres and additional involvement of the brainstem, basal ganglia and thalamus on MRI. Initially, she was considered to suffer from an autoimmune encephalitis, transiently responded to immunosuppression but then developed multiple solid appearing cerebral lymphomas.",,"Lewerenz, J.;Ding, X. Q.;Matschke, J.;Schnabel, C.;Emami, P.;von Borczyskowski, D.;Buchert, R.;Krieger, T.;de Wit, M.;Munchau, A.",2009,,10.1136/bcr.08.2008.0752,0,
2973,CADASIL patient with extracellular calcium deposits,"We report the case of a 57-year-old male patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) diagnosed on the basis of ultrastructural and genetic examinations. Ultrastructurally, granular osmiophilic material (GOM) deposits, degeneration and loss of vascular smooth muscle cells (VSMC) and pericytes in small arterial and capillary vessels from skin-muscle biopsy typical of CADASIL were visible. Degeneration of pericytes and endothelial cells were often pronounced, which resulted in a complete disappearance of mural cells and extremely severe thickening of the basement membrane. Degenerative changes in blood vessels, especially evident in skeletal muscle arterioles, also included significant vacuolization of VSMC, misshapen nuclei both in vessel wall cells and skeletal muscle fibres, and deposits of a hyaline material and calcium in the vessel wall. Abundant calcium deposits were located in the vascular basement membrane and exhibited laminar morphology with abnormally arranged light and dark bands. In the basement membrane of the most severely affected microvessels, only clusters of calcium deposits and remnants of the mural cells were observed. Laminar calcifications were also observed within the basement membrane surrounding skeletal muscle fibres. Such abundant calcium deposits in CADASIL have not as yet been described. Morphological findings, described in this report, expand the spectrum of histopathological changes in this genetically determined angiopathy.",calcium;hyalin;Notch3 receptor;osmium;abdominal aorta aneurysm;adult;article;attention disturbance;basement membrane;behavior change;blood vessel;blood vessel wall;brain ischemia;CADASIL;calcification;capillary;case report;cell degeneration;cognitive defect;coronary artery disease;endothelium cell;epilepsy;executive function;exon;extracellular calcium;family history;gene mutation;genetic analysis;headache;heart aneurysm;heart failure;hemiparesis;human;human tissue;male;memory disorder;microscopy;microvasculature;middle aged;migraine;mood disorder;morphology;muscle biopsy;neurologic examination;nuclear magnetic resonance imaging;pericyte;pseudobulbar palsy;skeletal muscle;skin biopsy;smooth muscle fiber;ultrastructure;vascular smooth muscle;white matter,"Lewandowska, E.;Wierzba-Bobrowicz, T.;Buczek, J.;Gromadzka, G.;Dziewulska, D.",2013,,,0,
2974,Ultrastructural picture of blood vessels in muscle and skin biopsy in CADASIL,"Cadasil (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is an inherited systemic vascular disorder affecting mainly the central nervous system. We performed detailed ultrastructural examination of the small vessels in the skin and skeletal muscle of a 51-year-old patient with bilateral cerebral white matter lesions, who had a history of two ischaemic strokes. The arterioles were characterized by degeneration and loss of vascular smooth muscle cells (VMMCs). GOM deposits, varied in size and shape, were located in the neighbourhood of the smooth muscle cells, often within an infolding of the cell membrane. No apparent correlations between presence, size or number of GOM deposits and damage severity of vascular smooth muscle cells were seen. Moreover, in some capillaries there were GOM deposits which were seen in the basement membrane near pericytes and endothelial cells. On the other hand, lesions of VMSCs and/or endothelial cells were also visible on the sections of blood vessels devoid of GOM deposits. Genetic tests detected a mutation in exon 4 of the Notch3 gene. It confirmed the initial diagnosis which had been suggested on the basis of the clinical and MRI findings.",Notch3 receptor;adult;anamnesis;arteriole;article;basement membrane;blood vessel;brain damage;CADASIL;case report;cell degeneration;cell loss;cell membrane;cerebrovascular accident;disease severity;endothelium cell;exon;female;gene mutation;genetic analysis;human;human tissue;pericyte;skeletal muscle;skin biopsy;smooth muscle fiber;ultrastructure;vascular smooth muscle;white matter,"Lewandowska, E.;Leszczyńska, A.;Wierzba-Bobrowicz, T.;Skowrońska, M.;Mierzewska, H.;Pasennik, E.;Członkowska, A.",2006,,,0,
2975,Blood vessel ultrastructural picture in a CADASIL patient diagnosed at an advanced age,"We report the case of an 84-year-old male patient afflicted by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) showing minimal symptoms of disease. The patient was diagnosed on the basis of ultrastructural and genetic examinations. Ultrastructurally, a typical vascular pathology was found. However, in abnormal capillary vessel walls no granular osmiophilic material (GOM) was found. In the arteriole there were only a few GOM deposits that revealed various structures, of which only some resembled typical round GOM. The arteriolar walls showed severe damage, including fragmentation, degeneration and loss of vascular smooth muscle cells (VSMCs) with numerous deposits of elastin, mucosubstances, different granular debris, as well as collagen fibres in the basement membrane. Lysosomal inclusions with fingerprint morphology, atypical for CADASIL, were located in some of the VSMCs. Very old age at the onset of the disease may suggest that morphological changes in blood vessels, described in this report, may be due to both the disease and the patient's age. To our best knowledge it is the first description of pathology of blood vessels and GOM morphology in a CADASIL patient diagnosed at an advanced age.",Notch3 receptor;aged;arteriole;article;basement membrane;brain atrophy;CADASIL;case report;collagen fiber;daily life activity;exon;gene mutation;gene sequence;human;male;muscle biopsy;nuclear magnetic resonance imaging;skin biopsy;smooth muscle fiber;ultrastructure;vascular disease;vascular smooth muscle;very elderly;white matter lesion,"Lewandowska, E.;Felczak, P.;Buczek, J.;Gramza, K.;Rafałowska, J.",2014,,,0,
2976,Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis,"BACKGROUND AND PURPOSE: MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18). METHODS: An automated tissue segmentation protocol that was optimized for an elderly population, a brain regional parcellation procedure, and a lesion segmentation protocol were applied to measure tissue volumes (whole brain and regional lobar volumes) with and without lesion segmentation to quantify the volume of misclassified tissue. RESULTS: After application of the tissue segmentation protocol and lesion analysis, mean total percentage misclassified volume across all subjects was 2% (17.9 cm(3)) of whole brain volume (corrected for total intracranial capacity). Mean percentage of misclassified tissue volumes for the severe group was 4.8% of whole brain, which translates to a mean volume 42.2 cm(3). Gray matter volume was most overestimated in the severe group, where 6.4% of the total gray matter volume was derived from misclassified WMH. The regional analysis showed that frontal (41%, 7.4 cm(3)) and inferior parietal (18%, 3.25 cm(3)) lobes were most affected by tissue misclassification. CONCLUSIONS: MRI-based volumetric studies of Alzheimer Disease that do not account for WMH can expect an erroneous inflation of gray or white matter volumes, especially in the frontal and inferior parietal regions. To avoid this source of error, MRI-based volumetric studies in patient populations susceptible to hyperintensities should include a WMH segmentation protocol.","Aged;Aging/ pathology;Alzheimer Disease/ pathology;Diagnostic Errors;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging/ methods/ standards;Nerve Fibers, Myelinated/ pathology;Parietal Lobe/pathology","Levy-Cooperman, N.;Ramirez, J.;Lobaugh, N. J.;Black, S. E.",2008,Apr,,0,2977
2977,Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis,"BACKGROUND AND PURPOSE: MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18). METHODS: An automated tissue segmentation protocol that was optimized for an elderly population, a brain regional parcellation procedure, and a lesion segmentation protocol were applied to measure tissue volumes (whole brain and regional lobar volumes) with and without lesion segmentation to quantify the volume of misclassified tissue. RESULTS: After application of the tissue segmentation protocol and lesion analysis, mean total percentage misclassified volume across all subjects was 2% (17.9 cm(3)) of whole brain volume (corrected for total intracranial capacity). Mean percentage of misclassified tissue volumes for the severe group was 4.8% of whole brain, which translates to a mean volume 42.2 cm(3). Gray matter volume was most overestimated in the severe group, where 6.4% of the total gray matter volume was derived from misclassified WMH. The regional analysis showed that frontal (41%, 7.4 cm(3)) and inferior parietal (18%, 3.25 cm(3)) lobes were most affected by tissue misclassification. CONCLUSIONS: MRI-based volumetric studies of Alzheimer Disease that do not account for WMH can expect an erroneous inflation of gray or white matter volumes, especially in the frontal and inferior parietal regions. To avoid this source of error, MRI-based volumetric studies in patient populations susceptible to hyperintensities should include a WMH segmentation protocol.","Aging [pathology];Alzheimer Disease [pathology];Diagnostic Errors;Frontal Lobe [pathology];Magnetic Resonance Imaging [methods] [standards];Nerve Fibers, Myelinated [pathology];Parietal Lobe [pathology];Aged[checkword];Humans[checkword]","Levy-Cooperman, N.;Ramirez, J.;Lobaugh, N. J.;Black, S. E.",2008,,10.1161/strokeaha.107.498196,0,
2978,"Parkinson's disease, ischemic stroke, dementia, and cranial computed tomography: Preliminary study","We sought to determine whether clinical features, stroke profiles, and cranial computed tomography (CCT) findings differed in nondemented and demented Parkinson's disease (PD) patients. Data were collected from our previously published case-control review of 119 idiopathic PD patients discharged from our Veterans Affairs Medical Center Neurology Service from 1982 through 1990. Historical, physical, age, age at onset of PD, duration of PD, motor severity, frequency of ischemic stroke and stroke risk factors, modified Hachinski Ischemic Score (MHIS), and CCT findings were recorded. We previously estimated that the number ofpatients with PD and dementia was 31 of 119 (26%) from our case-control review of idiopathic PD patients. Eighty-two male PD patients, 31 demented and 51 nondemented, had CCT data available for review. Demented PD patients were older (p < 0.01), had fewer normal CT scans (p = 0.0004), and more cerebral atrophy and leuko-araiosis (p = 0.0003) than nondemented PD patients. Clinical atherosclerosis did not significantly distinguish the groups, but 9 of 31 (29%) demented PD patients had a modified HIS >/= 5 and thus suggestive of, at least, multi-infarct dementia. Demented PD patients were older overall at PD onset, but did not appear to have significantly longer PD duration or more motor severity. Demented PD patients were also apt to have had a much more current CCT (p < 0.01) than nondemented patients. Although clinical atherosclerosis did not clearly separate groups, more than one-quarter of demented PD patients seem to have components of vascular dementia.",,"Levine, R. L.;Jones, J. C.;Bee, N.",1994,,10.1016/s1052-3057(10)80113-2,0,
2979,Clinical work-up for cognitive disorders and falls leading to the diagnosis of CADA SIL-type cerebral angiopathy,"CADASIL disease is a rare autosomal dominant hereditary angiopathy, primarily characterized by significant white matter damage on MRI. We have herein described a case of Cadasil disease discovered somewhat fortuitously, owing to its insidious symptom onset and the causal mutation's strongly suspected transmission to the patient's son.",article;CADASIL;cognitive defect;disease transmission;falling;human;nuclear magnetic resonance imaging,"Levecque, E.;Cals, N.",2016,,,0,
2980,Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults,"OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings. APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15% and worsening white matter grade in 27%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses. CONCLUSIONS: Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ.",0 (Antihypertensive Agents);Age Factors;Aged;Antihypertensive Agents/therapeutic use;Blood Pressure/drug effects;Cerebral Infarction/diagnostic imaging/ epidemiology/physiopathology;Disease Progression;Female;Heart Rate;Humans;Hypertension/diagnosis/drug therapy/ epidemiology/physiopathology;Incidence;Leukoaraiosis/diagnostic imaging/ epidemiology/physiopathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Prospective Studies;Pulsatile Flow;Risk Factors;Time Factors;United States/epidemiology;blood pressure;hypertension;leukoaraiosis,"Leung, L. Y.;Bartz, T. M.;Rice, K.;Floyd, J.;Psaty, B.;Gutierrez, J.;Longstreth, W. T., Jr.;Mukamal, K. J.",2017,Aug,,0,
2981,Diagnosis and assessment of dementia using functional brain imaging,"Functional brain imaging using computer-analyzed electroencephalography was performed in 40 subjects: 15 with mild-to-moderate dementia of the Alzheimer's type (DAT), 13 with mild-to-moderate multi-infarct dementia (MID), and 12 age-matched controls. We examined three different parameters of brain electrical activity in these subjects: absolute slow-wave power, proportional power in all frequency bands, and ratios of high-frequency/low-frequency electrical activity (so-called ""spectral ratios""). Spectral ratios were significantly more powerful in discriminating among groups than the other measures. Functional images using spectral ratios revealed that subjects with DAT have a characteristic left temporo-parietal defect which clearly distinguished them from subjects with MID and from control subjects. The severity of dementia was best assessed by examining absolute slow-wave power, which had the strongest linear correlation with mental status testing. Serial images from one subject with DAT over 3 years demonstrate both quantitative and qualitative shifts in slow-wave activity in the course of DAT. The study suggests that functional imaging may be more useful than either simple EEG or computer-analyzed EEG in assessing and diagnosing patients with suspected dementia.",,"Leuchter, A. F.;Walter, D. O.",1989,1989,,0,
2982,Effect of white matter disease on functional connections in the aging brain,"Periventricular white matter hyperintensities (PVHs) seen on T2 weighted MRI studies are common in elderly people and often represent demyelination of fibres. Damage to these fibres could lead to functional disconnection between brain regions. Electroencephalographic coherence, a measure of shared electrical activity between regions, was examined to determine if there was evidence for such disconnection. Twenty two subjects with clinically diagnosed dementia of the Alzheimer's type, 16 with multi-infarct dementia, and 18 normal controls were studied. It was hypothesised that coherence between areas presumably linked by fibres that traverse the periventricular region would be decreased in subjects with PVHs, and that PVHs would have a stronger association with decreased coherence than clinical diagnosis. It was also hypothesised that coherence between areas presumably connected by long corticocortical tracts that are neuroanatomically separated from the ventricles would be low in patients with Alzheimer's disease because of pyramidal cell death in this group, but would not be affected by the presence of PVHs. Patients with PVHs in fact had lower coherence than those without PVHs in the pre-Rolandic and post-Rolandic areas, where connecting fibres traverse the periventricular region. There was no effect of PVHs, however, on coherence between areas separated by the Rolandic fissure that were connected by long corticocortical tracts; this coherence was lowest among the patients with Alzheimer's disease. These patterns of association suggest that coherence may detect different types of neurophysiological ""disconnection,"" and may be sensitive to selective damage to different fibre pathways.","Aged;Alzheimer Disease/*diagnosis/*physiopathology;Brain/*physiopathology;Dementia, Multi-Infarct/*diagnosis/*physiopathology;Electroencephalography;Functional Laterality;Humans;Magnetic Resonance Imaging;*Neural Conduction;Neural Pathways/*physiopathology;Psychiatric Status Rating Scales;Severity of Illness Index","Leuchter, A. F.;Dunkin, J. J.;Lufkin, R. B.;Anzai, Y.;Cook, I. A.;Newton, T. F.",1994,Nov,,0,
2983,"Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases","The distribution of parvalbumin (PV), calretinin (CR), and calbindin (CB) immunoreactive neurons was studied with the help of an image analysis system (Vidas/Zeiss) in the primary visual area 17 and associative area 18 (Brodmann) of Alzheimer and control brains. In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter. Significant differences in the mean densities (numbers per square millimeter of cortex) of PV, CR, and CB immunoreactive neuronal profiles were not observed either between groups or areas, but only between superficial, middle, and deep layers within areas 17 and 18. The optical density of the immunoreactive neuropil was also similar in Alzheimer and controls, correlating with the numerical density of immunoreactive profiles in superficial, middle, and deep layers. The frequency distribution of neuronal areas indicated significant differences between PV, CR, and CB immunoreactive neuronal profiles in both areas 17 and 18, with more large PV than CR and CB positive profiles. There were also significantly more small and less large PV and CR immunoreactive neuronal profiles in Alzheimer than in controls. Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/pathology;Calbindin 2;Calbindins;Case-Control Studies;Female;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Male;Middle Aged;Nerve Tissue Proteins/ analysis;Neurons/ chemistry;Neuropil/chemistry;Parvalbumins/analysis;Reference Values;S100 Calcium Binding Protein G/analysis;Visual Cortex/ chemistry/cytology","Leuba, G.;Kraftsik, R.;Saini, K.",1998,Aug,10.1006/exnr.1998.6838,0,
2984,"Two clinicopathological cases of a dominantly inherited, adult onset orthochromatic leucodystrophy","Leucodystrophies of orthochromatic type are a heterogeneous group that occur mainly in childhood and have no known enzyme deficiency. We report here the clinico-pathological features of a new family of orthochromatic leucodystrophy with three main characteristics: a probably autosomal dominant inheritance; two phenotypes based on age of onset; and very few abnormalities of white matter on MRI findings in one case. The first patient, aged 58 years, had frontal dementia and epilepsy; the second, aged 38 years, had motor signs and dementia, but no epilepsy. The histopathological features of our two cases were leucodystrophy of orthochromatic subtype. However, the radiological features (MRI and mostly FLAIR sequences) of the first case did not suggest leucodystrophy.",adult;article;autosomal dominant disorder;case report;clinical feature;dementia;diagnostic imaging;female;histopathology;human;leukodystrophy;male;motor dysfunction;nuclear magnetic resonance imaging;onset age;orthochromatic leukodystrophy;phenotype;priority journal;radiodiagnosis;white matter,"Letournel, F.;Etcharry-Bouyx, F.;Verny, C.;Barthelaix, A.;Dubas, F.",2003,,,0,
2985,Brain injury and cognitive function in late-onset psychotic depression,"Fourteen patients who developed a psychotic depression after age 45 were compared with 72 non-psychiatrically ill elderly control subjects using neuroimaging and neuropsychological (NP) tests. Despite the fact that the patients were not studied if they had an obvious dementia or neurological disease, structural brain abnormalities were found in approximately two-thirds of patients and in less than 10% of controls. The most common abnormality, subcortical white matter (WM) lesions, was thought to be vascular in etiology. Also, tumor and primary degenerative dementia were found more frequently in the patients. Compared to an age-, sex-, and education-matched control group, the patients performed more poorly on NP tests of frontal lobe, memory, and visual spatial abilities. Diagnostic evaluation of the patient with late-onset psychotic depression should include computed tomography or magnetic resonance imaging as structural brain abnormalities are common in these patients.",Sr-inj,"Lesser, I. M.;Miller, B. L.;Boone, K. B.;Hill Gutierrez, E.;Mehringer, C. M.;Wong, K.;Mena, I.",1991,,,0,
2986,From gene to disease; from Notch3 to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,'Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) is an autosomal dominant inherited arteriopathy leading to brain infarcts and dementia at middle age with extensive cerebral white matter changes on MRI. CADASIL is caused by mutations in the Notch3 gene on chromosome 19.,Notch receptor;article;autosomal dominant disorder;brain infarction;cerebral artery disease;chromosome 19;dementia;gene mutation;human;leukoencephalopathy;onset age;white matter,"Lesnik Oberstein, S. A. J.;Bakker, E.;Ferrari, M. D.;Haan, J.",2001,,,0,
2987,Cerebral microbleeds in CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been described sporadically in patients with CADASIL, suggesting that the affected arteries in CADASIL are not bleed-prone. However, the presence of cerebral microbleeds, which often remain undetected on conventional MRI, has not been determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient echo MRI, which is highly sensitive for visualizing microbleeds, was performed in patients with CADASIL and their family members (n = 63). Known risk factors for ICH were determined for all individuals. On an exploratory basis, the presence of cerebral microbleeds was correlated with demographic variables, vascular risk factors, disease progression, ischemic MR lesions, and genotype. RESULTS: Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation carriers, predominantly in the thalamus. Vascular risk factors such as hypertension did not account for the microbleeds in these patients. Factors associated with microbleeds were age (p = 0.008), Rankin disability score (p = 0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the Arg153Cys mutation remained significantly associated with the presence of microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk of intracerebral microbleeds. This implies that they may have an increased risk for ICH, which should be taken into account in CADASIL diagnosis and patient management.","Adult;Brain/pathology;Cerebral Hemorrhage/*diagnosis/genetics;Dementia, Multi-Infarct/*diagnosis/genetics;Female;Genotype;Humans;*Image Enhancement;*Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Sensitivity and Specificity","Lesnik Oberstein, S. A.;van den Boom, R.;van Buchem, M. A.;van Houwelingen, H. C.;Bakker, E.;Vollebregt, E.;Ferrari, M. D.;Breuning, M. H.;Haan, J.",2001,Sep 25,,0,
2988,Incipient CADASIL,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.","Adult;Dementia, Multi-Infarct/epidemiology/genetics/ radiography;Female;Humans;Magnetic Resonance Imaging;Male;Migraine with Aura/epidemiology/genetics/radiography;Neuropsychological Tests;Predictive Value of Tests;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface;Receptors, Notch;Risk Factors;Stroke/epidemiology/genetics/radiography","Lesnik Oberstein, S. A.;van den Boom, R.;Middelkoop, H. A.;Ferrari, M. D.;Knaap, Y. M.;van Houwelingen, H. C.;Breuning, M. H.;van Buchem, M. A.;Haan, J.",2003,May,10.1001/archneur.60.5.707,0,
2989,Fourier transform infrared imaging showing reduced unsaturated lipid content in the hippocampus of a mouse model of Alzheimer's disease,"Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic =CH stretching mode at 3012 cm(-1). The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p < 0.01) but remained low and relatively constant in PSAPP mice. Thus, these findings indicate that unsaturated lipid content is reduced in hippocampal white matter during amyloid pathogenesis and that maintaining unsaturated lipid content early in the disease may be critical in avoiding progression of the disease.","Alzheimer Disease/ metabolism;Animals;Disease Models, Animal;Fatty Acids, Unsaturated/ analysis/chemistry;Hippocampus/chemistry/ metabolism/pathology;Humans;Mice;Oxidation-Reduction;Principal Component Analysis;Spectroscopy, Fourier Transform Infrared/ methods","Leskovjan, A. C.;Kretlow, A.;Miller, L. M.",2010,Apr 1,10.1021/ac1002728,0,
2990,Lymphomatosis cerebri presenting as a rapidly progressive dementia with a high methylmalonic acid,"We report a case of a patient with a rapidly progressive dementing illness and gait disturbance, in whom initial screening demonstrated a high methylmalonic acid level only, suggestive of a functional vitamin B(12) deficiency. Despite B(12) replacement therapy, he continued to decline. Further investigations demonstrated extensive signal change on magnetic resonance imaging involving grey and white matter within the corpus callosum, deep grey matter, brainstem and cerebellar peduncles, and patchy post-contrast enhancement. Laboratory testing revealed a raised erythrocyte sedimentation rate, raised anti-nuclear, intrinsic factor and lupus anticoagulant antibody titres, and a IgG kappa paraprotein. Cerebrospinal fluid was unremarkable. Bone marrow trephine biopsy showed monoclonal gammopathy of unknown significance. The patient initially responded to steroids, and underwent a brain biopsy, which was uninformative. However, 3 weeks following admission, he died due to an aspiration pneumonia. Autopsy findings were consistent with a diffuse primary central nervous system small cell B-cell lymphoma. This has been rarely reported in the medical literature, but our case exhibits typical clinical features, although patchy enhancement on imaging and the high methylmalonic acid have not been previously described. We hypothesise that his functional B(12) deficiency may have resulted from rapid cell turnover, perhaps in conjunction with the presence of intrinsic factor antibodies. © 2011 Springer-Verlag.",,"Leschziner, G.;Rudge, P.;Lucas, S.;Andrews, T.",2011,August,,0,
2991,Associations between T(1) white matter lesion volume and regional white matter microstructure in aging,"White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43-85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. © 2013 Wiley Periodicals, Inc.",,"Leritz, E. C.;Shepel, J.;Williams, V. J.;Lipsitz, L. A.;McGlinchey, R. E.;Milberg, W. P.;Salat, D. H.",2014,March,,0,
2992,Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection,"OBJECTIVE: To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations. METHODS: Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification. RESULTS: Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8+ T cells, especially effector CD8+ T cells. CONCLUSIONS: These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8+ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus-host interactions involved in CNS functional deficits.",AIDS Dementia Complex/diagnosis/immunology/ metabolism;Adult;Aspartic Acid/analogs & derivatives/analysis/metabolism;Biomarkers/analysis/metabolism;Brain/immunology/ metabolism/physiopathology;CD4-CD8 Ratio;Disease Progression;Early Diagnosis;Frontal Lobe/immunology/metabolism/physiopathology;Glutamic Acid/analysis/metabolism;HIV Seropositivity/complications;Humans;Immunophenotyping;Magnetic Resonance Spectroscopy/ methods;Middle Aged;Neurons/immunology/ metabolism;T-Lymphocytes/immunology/ metabolism,"Lentz, M. R.;Kim, W. K.;Lee, V.;Bazner, S.;Halpern, E. F.;Venna, N.;Williams, K.;Rosenberg, E. S.;Gonzalez, R. G.",2009,Apr 28,10.1212/WNL.0b013e3181a2e90a,0,
2993,Alterations in brain metabolism during the first year of HIV infection,"Migration of both uninfected and infected monocytes into the brain during acute HIV infection likely initiates metabolic changes that can be observed with magnetic resonance spectroscopy (MRS). Herein, we measured changes in brain metabolism during the first year of HIV infection and examined the relationship of these metabolite levels to CD16+ monocyte populations measured in the blood. MRS was performed on nine HIV+ subjects identified during acute HIV infection and nine seronegative control subjects. HIV+ subjects were examined within 90 days of an indeterminate Western blot, then again 2 and 6 months later, during early infection. Blood samples were collected for plasma viral RNA and monocyte subset quantification. HIV+ subjects were identified with acute viral ailment and did not display severe cognitive deficits such as dementia or minor cognitive motor disorder. Changes in lipid membrane metabolism (choline levels) in the frontal cortex and white matter were observed during the initial year of HIV infection. Greater numbers of CD16+ monocytes were associated with lower N-acetylaspartate levels and higher choline levels in the brain. These results suggest that HIV infection induces metabolic changes in the brain early during infection and that these changes may be related to monocyte dynamics in the periphery. © Journal of NeuroVirology, Inc. 2011.",abacavir plus lamivudine plus zidovudine;CD16 antigen;choline;efavirenz;efavirenz plus emtricitabine plus tenofovir disoproxil;emtricitabine plus tenofovir disoproxil;lamivudine;lamivudine plus zidovudine;lopinavir plus ritonavir;n acetylaspartic acid;tenofovir disoproxil;virus RNA;adult;article;brain metabolism;brain region;clinical article;controlled study;dementia;frontal cortex;human;Human immunodeficiency virus infection;lipid membrane;lipid metabolism;male;monocyte;motor dysfunction;nuclear magnetic resonance spectroscopy;priority journal;Western blotting;white matter;atripla;combivir;epivir;kaletra;sustiva;trizivir;truvada,"Lentz, M. R.;Kim, W. K.;Kim, H.;Soulas, C.;Lee, V.;Venna, N.;Halpern, E. F.;Rosenberg, E. S.;Williams, K.;González, R. G.",2011,,,0,
2994,Association of apolipoprotein E epsilon2 with white matter disease but not with microbleeds,"BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) alleles (epsilon2 and epsilon4) are associated with cerebral amyloid angiopathy, in which white matter disease and microbleeds are prominent features. The role of apoE in patients with microbleeds or white matter disease but no evidence of cerebral amyloid angiopathy has not been elucidated. We studied apoE alleles in relation to white matter disease and microbleeds in patients with transient ischemic attack or ischemic stroke. METHODS: We obtained brain MRI scans and apoE genotypes in 334 transient ischemic attack or ischemic stroke patients. Microbleeds were scored on a gradient echo MRI and white matter disease was examined on fluid attenuated inversion recovery MRI using a semiquantitative rating scale. RESULTS: Patients with moderate to severe white matter disease more frequently carried apoE epsilon2 alleles (25.2% versus 11.3%, P=0.001), but not apoE epsilon4 (26.6% in apoE epsilon4 carriers versus 25.9%; P=0.98). Adjustment for traditional risk factors did not modify this relationship (odds ratio, 2.9; 95% confidence interval, 1.5 to 5.3). There was no association between the presence of microbleeds and the apoE epsilon4 or apoE epsilon2 alleles. CONCLUSIONS: ApoE alleles do not exert a major influence on the development of microbleeds, but apoE epsilon2 may be associated with development of moderate to severe white matter disease in transient ischemic attack and stroke patients.","Aged;Apolipoprotein E2/blood/*genetics;Apolipoprotein E4/blood/genetics;Belgium;Brain/metabolism/pathology/physiopathology;Cerebral Arteries/*metabolism/physiopathology;Cerebral Hemorrhage/blood/*genetics/physiopathology;Cholesterol/*metabolism;Cohort Studies;DNA Mutational Analysis;Dementia, Vascular/blood/*genetics/physiopathology;Female;Gene Frequency/genetics;Genetic Markers/genetics;Genetic Predisposition to Disease/*genetics;Genetic Testing;Genotype;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/metabolism/pathology;Prospective Studies;Risk Factors","Lemmens, R.;Gorner, A.;Schrooten, M.;Thijs, V.",2007,Apr,10.1161/01.str.0000259816.31370.44,0,
2995,Atypical white matter changes in Alzheimer's disease,,adult;Alzheimer disease;article;brain disease;case report;human;male;nuclear magnetic resonance imaging;priority journal;psychosis;seizure;white matter,"Leker, R. R.;River, Y.",1997,,,0,
2996,Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease,"Purpose. Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. Methods. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. Results. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with 18FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagnostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Conclusion. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD.",fluorodeoxyglucose f 18;Alzheimer disease;amygdaloid nucleus;article;brain atrophy;brain region;corpus callosum;diagnostic accuracy;disease course;disease severity;glucose metabolism;hippocampus;human;neocortex;nerve degeneration;nuclear magnetic resonance imaging;positron emission tomography;receiver operating characteristic;volumetry,"Leinsinger, G.;Teipel, S.;Wismüller, A.;Born, C.;Meindl, T.;Flatz, W.;Schönberg, S.;Pruessner, J.;Hampel, H.;Reiser, M.",2003,,,0,
2997,Neuroimaging in dementia,"Imaging is a part of the work-up for all types of dementia. X-ray computed tomography (CT) is a first-line examination to rule out causes of surgical, and thus reversible, dementia (for example, subdural hematoma or normal pressure hydrocephalus). MRI (magnetic resonance imaging) is preferred for work-ups of dementia. In the neurodegenerative dementias, the topography of the atrophy provides information about the specific type: atrophy of the medial temporal lobe is predominant in Alzheimer disease, while atrophy of the frontal and anterior temporal lobes is seen in frontotemporal dementia, with less medial temporal atrophy than in Alzheimer disease for frontotemporal dementia; vascular dementia is marked by infarction, lacuna, and signal abnormalities in the white matter and sometimes microbleeding. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are used in clinically atypical forms. Study of the dopamine transporter (DATscan(®)) is used to distinguish Lewy body dementia from Alzheimer disease. Numerous studies are underway to identifying specific imaging markers for different types of dementia, including cerebral volumetric measurements, diffusion imaging, spectroscopy, very-high-field MRI scans of senile plaques, and PET markers of senile plaques. © 2007 Elsevier Masson SAS. All rights reserved.",,"Lehéricy, S.;Delmaire, C.;Galanaud, D.;Dormont, D.",2007,October,,0,
2998,Microbleeds are associated with depressive symptoms in Alzheimer's disease,"Introduction Co-occurrence of cerebrovascular disease and depression led to the “vascular depression hypothesis”. White matter hyperintensities (WMHs) have been associated with depressive symptoms in population-based studies. We studied the association between small vessel disease and depressive symptoms in a memory clinic population. Methods We included >2000 patients with subjective cognitive decline (SCD), mild cognitive impairment, and Alzheimer's disease (AD). Magnetic resonance imaging was rated for WMHs, lacunes, and microbleeds. Depressive symptoms were assessed using the Geriatric Depression Scale. We performed logistic regression analysis. Results Depressive symptoms were present in AD: 17%; mild cognitive impairment: 25%; and SCD: 23%. SCD patients with WMHs showed higher propensity of depressive symptoms than AD patients with WMHs. AD patients with microbleeds were more likely to have depressive symptoms compared with AD patients without microbleeds (odds ratio = 1.70; 95% confidence interval: 1.08–2.68). Discussion Microbleeds are associated with depressive symptoms in AD, supporting a potential role of cerebral amyloid angiopathy in the occurrence of depressive symptoms in AD.",adult;aged;Alzheimer disease;article;brain hemorrhage;cognitive defect;controlled study;depression;disease association;female;Geriatric Depression Scale;human;major clinical study;male;middle aged;mild cognitive impairment;nervous system parameters;nuclear magnetic resonance imaging;radiological parameters;subjective cognitive decline;white matter hyperintensity,"Leeuwis, A. E.;Prins, N. D.;Hooghiemstra, A. M.;Benedictus, M. R.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.",2018,,10.1016/j.dadm.2017.11.006,0,
2999,Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts,"Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an inherited neurologic disorder with macrocephaly before the age of one and slowly progressive deterioration of motor functions. Magnetic resonance imaging shows diffusely abnormal and swollen white matter of the cerebral hemispheres and the presence of subcortical cysts in the anterior-temporal region and often also in the frontoparietal region. Mutations in the MLC1 gene, encoding a putative membrane protein, have been recently identified as a cause for MLC. Here, we describe 14 new mutations in 18 patients. Two identified polymorphisms lead to alterations of amino acid residues. The role, suggested by others, of a mutation in the MLC1gene in catatonic schizophrenia and the possible function of the MLC1 protein as a cation channel are discussed.","Amino Acid Sequence;Animals;Base Sequence;Central Nervous System Cysts/genetics/pathology;DNA/genetics;DNA Mutational Analysis;Dementia, Vascular/ genetics/pathology;Exons;Heredodegenerative Disorders, Nervous System/ genetics/pathology;Humans;Membrane Proteins/ genetics;Mice;Molecular Sequence Data;Mutation;Potassium Channels/genetics;Schizophrenia, Catatonic/genetics;Sequence Homology, Amino Acid;Sequence Homology, Nucleic Acid","Leegwater, P. A.;Boor, P. K.;Yuan, B. Q.;van der Steen, J.;Visser, A.;Konst, A. A.;Oudejans, C. B.;Schutgens, R. B.;Pronk, J. C.;van der Knaap, M. S.",2002,Mar,10.1007/s00439-002-0682-x,0,
3000,"Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese","BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan. METHODS: Mutational analysis of NOTCH3 exons 2 to 23 by direct nucleotide sequencing was performed in patients with clinically suspected CADASIL. MRI findings were retrospectively evaluated and scored using a modified Schelten's scale. RESULTS: Nine different point mutations of NOTCH3 were identified in 21 unrelated patients. Intriguingly, 47.6 % were in exon 11, and 19 % in each of exon 4 and 18. R544C was very common and present in all patients with a mutation in exon 11. Many patients with NOTCH3 R544C share the same haplotype linked to the mutation using markers D19S929 and D19S411, which flank the NOTCH3. The sensitivity of T2-weighted MRI detecting anterior temporal abnormality was only 42.9 %. Furthermore, the neuroimaging evidence of intracerebral hemorrhage (ICH) was present in 23.8 % of the 21 patients. CONCLUSIONS: A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.","Adult;Aged;Asian Continental Ancestry Group/ethnology/genetics;Brain/metabolism/*pathology/physiopathology;CADASIL/ethnology/*genetics/*pathology;DNA Mutational Analysis;Female;Founder Effect;Gene Frequency/genetics;Genetic Markers/genetics;Genetic Predisposition to Disease/*genetics;Genetic Testing;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/*genetics;Receptors, Notch/*genetics;Taiwan","Lee, Y. C.;Liu, C. S.;Chang, M. H.;Lin, K. P.;Fuh, J. L.;Lu, Y. C.;Liu, Y. F.;Soong, B. W.",2009,Feb,10.1007/s00415-009-0091-3,0,
3001,Visual Hallucination and Pattern of Brain Degeneration in Parkinson's Disease,"Background and Objectives: The incidence of visual hallucination (VH) increases with Parkinson's disease (PD) progression, and its development is thought to be related to a specific neurodegenerative process in PD. This study aimed to reveal brain degeneration related to VH in PD by analyzing neuroimaging data obtained from patients in their different stages of PD. Methods: Data from 48 PD patients-21 nondemented without VH (PNV group), 10 nondemented with VH (PV group), and 17 demented with VH (PVD group)-and 30 age-matched healthy controls (HC group) were analyzed. Voxel-based morphometry and tract-based spatial statistics were conducted. Previous magnetic resonance volumetric studies on VH in PD were collectively reviewed. Results: The PV group showed gray matter atrophy in the right inferior parietal lobule and supramarginal gyrus compared with the HC and PNV groups. The PVD group showed a wider range of gray matter atrophies in the temporo-parieto-occipital regions than those in the PV group. White matter changes seemed to be an earlier event than gray matter changes. Fractional anisotropy values diffusely decreased in all three PD subgroups compared with the HC group without significant differences between the PD subgroups. Mean diffusivity was not different between the PNV and HC groups but increased in the parieto-Temporal region in the PV group and increased diffusely in the PVD group, additionally including the fronto-occipital regions. A review of previous studies supported our observations. Conclusions: Gray matter degenerations from the parieto-Temporal junction to the parieto-occipital and temporo-occipital regions may be responsible for VH on the typical timeline of PD progression.",levodopa;aged;article;brain atrophy;brain degeneration;brain size;clinical article;controlled study;cuneus;diffusion tensor imaging;female;fractional anisotropy;gray matter;Hoehn and Yahr scale;human;inferior parietal lobule;inferior temporal gyrus;male;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance;nuclear magnetic resonance scanner;Parkinson disease;postcentral gyrus;precuneus;primary motor cortex;priority journal;superior temporal gyrus;supramarginal gyrus;Unified Parkinson Disease Rating Scale;visual hallucination;voxel based morphometry;white matter;Achieva,"Lee, W. W.;Yoon, E. J.;Lee, J. Y.;Park, S. W.;Kim, Y. K.",2017,,10.1159/000448517,0,
3002,Decreased vasomotor reactivity in Alzheimer's disease,"BACKGROUND: Reduced cerebral blood flow and microvascular abnormalities have been suggested as the vascular pathogenesis of Alzheimer's disease (AD). Transcranial Doppler sonography (TCD) can be used as a noninvasive method for measuring cerebral vasomotor reactivity (VMR) which represent the capability of arterioles to dilate and constrict in order to maintain cerebral blood flow. OBJECTIVE: The objective of this study was to determine whether VMR is decreased in AD patients. METHODS: Seventeen consecutive patients who met NINDS-ADRDA criteria for AD, and 17 age- and sex-matched controls were included in this study. MRI and MRA were performed for the grading of white-matter lesions. Patients with cerebral infarct or stenosis of the middle cerebral artery (MCA) were excluded. The fixed TCD probe was used to monitor the mean flow velocity (MFV) in the MCA. A 6-L rebreathing bag was applied to patients for at least 5 minutes to elevate the CO(2) concentration, which was continuously monitored with a capnometer. VMR was calculated as the percentage change in the MFV. RESULTS: Baseline characteristics - including cerebrovascular risk factors, grades of white-matter lesions, baseline MFV, and pulsatility index - did not differ between the two groups. Mini-Mental State Examination score was significantly low in AD group (20.5 vs. 27.5, p<0.05). VMR was significantly reduced in AD group both in the right-side (24.5% vs. 36.6%, p<0.05) and left-side (20.7% vs. 34.1%, p<0.05) MCAs. CONCLUSIONS: Our finding that VMR is reduced in AD may be suggestive of underlying microangiopathic mechanism in AD patients. Future studies should check the validity of these experimental and hypothesis-generating pilot results.",Alzheimer's disease;Cerebral blood flow;Transcranial Doppler sonography;Vasomotor reactivity,"Lee, S. T.;Jung, K. H.;Lee, Y. S.",2007,Mar,10.3988/jcn.2007.3.1.18,0,
3003,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy affecting an African American man: Identification of a novel 15-base pair NOTCH3 duplication,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best characterized genetic cause of vascular dementia and stroke and has been extensively reported in European and Asian populations. Objective: To report the pathological and genetic analysis of CADASIL in an African American man with a 15-base pair NOTCH3 duplication. Design: Case report. Setting: University hospital. Patient: A 78-year-old man with dementia, recurrent strokes, a family history of similar neurological disease, and white matter abnormalities seen on brain magnetic resonance imaging. Main Outcome Measures: Brain pathology and genetic analysis of NOTCH3. Results: The patient's brain showed widespread arteriopathy in large and small arteries. Using electron microscopy, granular osmiophilic material typical of CADASIL was identified abutting the plasma membrane of smooth muscle cells. Brain extracts contained elevated NOTCH3 protein levels. Sequencing of the NOTCH3 gene revealed a novel 15-base pair heterozygous duplication in exon 7, which is predicted to direct expression of a protein that contains 5 extra amino acids, including a cysteine residue. Conclusions: To our knowledge, this is the first reported pathological and genetic analysis of an African American patient with CADASIL. The mutation in NOTCH3 is the longest duplication within this gene yet reported. ©2011 American Medical Association. All rights reserved.",,"Lee, S. J.;Meng, H.;Elmadhoun, O.;Blaivas, M.;Wang, M. M. H.",2011,December,,0,
3004,Apparent relative hypermetabolism of selective brain areas in Huntington disease and importance of reference region for analysis,"PURPOSE: We investigated the pattern of reduced and increased metabolism in symptomatic Huntington chorea (HD) patients and assessed the influence of intensity normalization method. PATIENTS AND METHODS: FDG brain PET was performed in 11 manifest HD patients and 11 age-matched controls. Images underwent statistical parametric mapping analysis after global normalization or with white matter or pons as reference region. Region of interest analysis of FDG uptake ratios was also performed using total region or white matter as reference. Correlation between regional uptake ratios to that of the caudate was evaluated by linear regression analysis. RESULTS: Although statistical parametric mapping analysis identified striatal hypometabolism and thalamic hypermetabolism in HD patients with all methods, substantially different FDG uptake patterns were shown depending on the method of intensity normalization. Global normalization displayed large areas of relative normalized hypermetabolism across the cerebral cortex and cerebellum. With white matter as reference, relative normalized hypermetabolism was observed in the thalamus and a much more limited area of the cortex. With pons as reference, relative normalized hypermetabolism was largely confined to the thalamus and a small area of the cerebellum. CONCLUSION: These results demonstrate apparent relative normalized hypermetabolism in selective brain regions in manifest HD patients. Furthermore, the choice of reference region for intensity normalization is critical for accurate monitoring of this metabolic change with FDG PET.",Brain/ metabolism/radionuclide imaging;Brain Mapping;Female;Fluorodeoxyglucose F18;Humans;Huntington Disease/ metabolism/radionuclide imaging;Male;Middle Aged;Positron-Emission Tomography;Reference Standards,"Lee, S. J.;Lee, W. Y.;Kim, Y. K.;An, Y. S.;Cho, J. W.;Choi, J. Y.;Kim, B. T.;Lee, K. H.",2012,Jul,10.1097/RLU.0b013e3182478bf2,0,
3005,The cross-sectional and longitudinal relationships between white matter hyperintensities and dementia in patients with Parkinson's disease: A retrospective analysis of 132 patients in a single center,"OBJECTIVE: To clarify the cross-sectional and longitudinal relationships between white matter hyperintensities (WMH) and dementia in Parkinson's disease (PD) patients. METHODS: One hundred thirty-two PD patients were included. Using medical records, the patient data including Hoehn and Yahr stage, postural instability, neuropsychological tests and magnetic resonance imaging were analyzed. The degree of WMH was rated according to a modified Fazekas scale. The relationship between the variables and dementia was analyzed using the independent t-test, the chi-square test, logistic regression analysis and the Cox proportional hazard model. RESULTS: The mean age of the study patients (35 males and 97 females) was 71.6 years (range, 45-93 years). The baseline WMH was associated not only cross-sectionally with the contemporary prevalence of dementia but also longitudinally with subsequent occurrence of dementia in the univariate analysis. These relationships became attenuated and statistically insignificant in the multivariate analysis after adjusting for confounders. It was postural instability that consistently predicted dementia in both the cross-sectional and the longitudinal data. CONCLUSIONS: Our study showed that baseline WMH was not independently associated with dementia, and instead postural instability revealed at first examination can be a more reliable predictor of dementia in PD patients.",Adult;Aged;Cross-Sectional Studies;Dementia/complications/ pathology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Neuropsychological Tests;Parkinson Disease/complications/ pathology;Proportional Hazards Models;Retrospective Studies;White Matter/ pathology,"Lee, S. J.;Lee, D. G.",2016,Jan-Feb,10.1016/j.archger.2015.10.006,0,
3006,Influence of white matter hyperintensities on the cognition of patients with parkinson disease,"BACKGROUND: White matter hyperintensities (WMH) have been associated with cognitive impairment in elderly persons and in patients with Alzheimer disease. However, the role of WMH in Parkinson disease (PD) dementia remains to be elucidated. METHODS: The cohort for this study comprised 71 consecutive patients with PD, all of whom completed a clinical assessment, neuropsychologic investigation, and magnetic resonance imaging of brain. WMH were rated using the semiquantitative visual rating system proposed by Scheltens et al. RESULTS: The PD dementia group had significantly more WMH than the PD without dementia group in the evaluated brain regions except for the infratentorial area. The WMH showed a significant correlation with age, Unified Parkinson s Disease Rating Scale, Mini-Mental State Examination, sum of the box of Clinical Dementia Rating, and many of the cognitive domains. The linear regression model showed that the WMH was independently associated with cognitive impairment in patients with PD, regardless of age, sex, duration or severity of PD symptoms, and vascular risk factors. CONCLUSIONS: These findings confirm that WMH might be associated with cognitive decline in patients with PD, regardless of age, sex, education status, duration or severity of PD symptoms, and vascular risk factors. This result suggests that other nonvascular factors contribute to the progression of dementia in patients with PD. © 2010 by Lippincott Williams & Wilkins.",,"Lee, S. J.;Kim, J. S.;Yoo, J. Y.;Song, I. U.;Kim, B. S.;Jung, S. L.;Yang, D. W.;Kim, Y. I.;Jeong, D. S.;Lee, K. S.",2010,July-September,,0,
3007,Paradoxical progression of intracranial tuberculomas and anterior cerebral artery infarction,,dexamethasone;isoniazid;pyrazinamide;rifampicin;streptomycin;adult;akinetic mutism;article;brain vasculitis;case report;cerebral artery disease;disease course;disease severity;female;headache;human;immunocompetence;intracranial tuberculoma;laboratory test;mental deterioration;miliary tuberculosis;nuclear magnetic resonance imaging;priority journal;treatment outcome;tuberculous meningitis;urine incontinence;vomiting,"Lee, S. I.;Park, J. H.;Kim, J. H.",2008,,,0,
3008,Reversible dementia in systemic lupus erythematosus without antiphospholipid antibodies or cerebral infarction,"Dementia is a very rare neurological manifestation of systemic lupus erythematosus (SLE) and has a deep link with antiphospholipid antibodies (APL) and cerebral infarction in its development. However, non-vascular dementia irrelevant to APL or cerebral infarction has not been reported in patients with SLE until now. We describe a case of reversible dementia in an SLE patient without APL or cerebral infarction which was successfully treated with corticosteroid and cyclophosphamide. There are two significant points in this case. One is that humoral factors other than APL might be involved in the development of dementia. Secondly, reversible dementia without APL or cerebral infarction may respond more favorably to immunosuppressive therapy.",antinuclear antibody;autoantibody;corticosteroid;cyclophosphamide;double stranded DNA;double stranded DNA antibody;hydroxychloroquine;methylprednisolone;prednisone;unclassified drug;adult;antiphospholipid syndrome;arthritis;article;brain infarction;case report;clinical feature;dementia;diagnostic imaging;female;fever;follow up;headache;human;humoral immunity;image analysis;immunosuppressive treatment;leukopenia;lymphocytopenia;myalgia;nuclear magnetic resonance imaging;photosensitivity;priority journal;symptom;systemic lupus erythematosus,"Lee, S. I.;Jeon, H. S.;Yoo, W. H.",2004,,,0,
3009,Differences in early and late mild cognitive impairment tractography using a diffusion tensor MRI,"Diffusion tensor MRI tractography is an imaging tool that can provide information of in-vivo neuronal fiber tracts to assess progress for Alzheimer's disease (AD). In an effort to detect early AD progression, we focused on distinguishing subgroups within mild cognitive impairment (MCI): early MCI and late MCI. Tractography was applied not only to white matter regions but also neighboring gray matter regions known to be affected by AD. Nerve fibers touching the hippocampus, thalamus, and amygdala in both hemispheres were extracted to quantify limbic system fiber connectivity. Two fiber extraction algorithms, fiber assignment by continuous tracking and the Runge Kutta approach, were applied to an AD imaging database. We computed the number of fibers touching regions of interest as the imaging feature. The imaging feature could distinguish between the MCI subgroups. It was also significantly correlated with a known genetic marker for AD, the apolipoprotein E epsilon 4 allele. The number of fibers might be a useful imaging biomarker to complement conventional region of interest-based biomarkers for AD research.","Aged;Algorithms;Alzheimer Disease/diagnosis/genetics/pathology;Apolipoprotein E4/genetics;Brain/ pathology;Databases, Factual;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Disease Progression;Female;Gray Matter/pathology;Humans;Image Processing, Computer-Assisted;Male;Mild Cognitive Impairment/genetics/ pathology;White Matter/pathology","Lee, S. H.;Seo, J.;Lee, J. M.;Park, H.",2014,Dec 3,10.1097/wnr.0000000000000279,0,
3010,Brain volumetry in Parkinson's disease with and without dementia: where are the differences?,"BACKGROUND: Cognitive dysfunction is well documented in Parkinson's disease (PD). However, association between regional brain volume change and cognitive decline of PD is uncertain. PURPOSE: To compare regional brain volume difference between PD without dementia (PDND) and PD with dementia (PDD). MATERIAL AND METHODS: We enrolled 16 normal controls (mean +/- SD: 69.5 +/- 6.31) and 32 sex-, age-matched patients with PD (16 PDND and 16 PDD patients with Hoehn & Yahr stage II or III). Cognitive function was assessed using mini-mental status examination (MMSE). Intracranial volume (ICV) and the hippocampal volumes were manually measured using magnetic resonance imaging (MRI). Regional gray/white matter volume changes were analyzed using voxel-based morphometry. RESULTS: Age, ICV, volume of gray matter volume (GMV), white matter, and hippocampi did not differ among the three groups. The regional GMV of PDD was significantly decreased in the areas of right middle frontal gyrus, short insular gyri, superior temporal gyri; both precuneus compared to PDND (uncorrected P < 0.001). In the partial correlation analysis (controlled for age, sex, ICV), regional GMV of PD was positively correlated with MMSE score in the areas of short insular gyri, right circular insular sulcus, right calcarine sulcus, left superior temporal gyrus (planum porale), and left inferior precentral sulcus (uncorrected P < 0.001). CONCLUSION: We suggest that the volume loss of hippocampus may not be a finding in developing of PDD while variation of the regional volume of the frontal, insular cortex, superior temporal gyri, and precuneus lobes may be a phenomenon of PDD.","Aged;Aged, 80 and over;Brain/ pathology;Case-Control Studies;Cognition Disorders/etiology/pathology;Dementia/complications/ pathology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Organ Size;Parkinson Disease/complications/ pathology;Parkinson's disease;dementia;gray matter;regional volume;white matter","Lee, S. H.;Kim, S. S.;Tae, W. S.;Lee, S. Y.;Lee, K. U.;Jhoo, J.",2013,Jun,,0,3011
3011,Brain volumetry in Parkinson's disease with and without dementia: where are the differences?,"BACKGROUND: Cognitive dysfunction is well documented in Parkinson's disease (PD). However, association between regional brain volume change and cognitive decline of PD is uncertain.PURPOSE: To compare regional brain volume difference between PD without dementia (PDND) and PD with dementia (PDD).MATERIAL AND METHODS: We enrolled 16 normal controls (mean ± SD: 69.5 ± 6.31) and 32 sex-, age-matched patients with PD (16 PDND and 16 PDD patients with Hoehn & Yahr stage II or III). Cognitive function was assessed using mini-mental status examination (MMSE). Intracranial volume (ICV) and the hippocampal volumes were manually measured using magnetic resonance imaging (MRI). Regional gray/white matter volume changes were analyzed using voxel-based morphometry.RESULTS: Age, ICV, volume of gray matter volume (GMV), white matter, and hippocampi did not differ among the three groups. The regional GMV of PDD was significantly decreased in the areas of right middle frontal gyrus, short insular gyri, superior temporal gyri; both precuneus compared to PDND (uncorrected P < 0.001). In the partial correlation analysis (controlled for age, sex, ICV), regional GMV of PD was positively correlated with MMSE score in the areas of short insular gyri, right circular insular sulcus, right calcarine sulcus, left superior temporal gyrus (planum porale), and left inferior precentral sulcus (uncorrected P < 0.001).CONCLUSION: We suggest that the volume loss of hippocampus may not be a finding in developing of PDD while variation of the regional volume of the frontal, insular cortex, superior temporal gyri, and precuneus lobes may be a phenomenon of PDD.",,"Lee, S. H.;Kim, S. S.;Tae, W. S.;Lee, S. Y.;Lee, K. U.;Jhoo, J.",1987,1,,0,
3012,Tract-based analysis of white matter degeneration in Alzheimer's disease,"Although much prior work has focused on the known cortical pathology that defines Alzheimer's disease (AD) histologically, recent work has additionally demonstrated substantial damage to the cerebral white matter in this condition. While there is large evidence of diffuse damage to the white matter in AD, it is unclear whether specific white matter tracts exhibit a more accelerated pattern of damage and whether the damage is associated with the classical neurodegenerative changes of AD. In this study, we investigated microstructural differences in the large fascicular bundles of the cerebral white matter of individuals with AD and mild cognitive impairment (MCI), using recently developed automated diffusion tractography procedures in the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset. Eighteen major fiber bundles in a total of 36 individuals with AD, 81 MCI and 60 control participants were examined with the TRActs Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the FreeSurfer image processing software package. For each fiber bundle, the mean fractional anisotropy (FA), and mean, radial and axial diffusivities were calculated. Individuals with AD had increased diffusivities in both left and right cingulum-angular bundles compared to control participants (p<0.001). Individuals with MCI also had increased axial and mean diffusivities and increased FA in both cingulum-angular bundles compared to control participants (p<0.05) and decreased radial diffusivity compared to individuals with AD (p<0.05). We additionally examined how white matter deterioration relates to hippocampal volume, a traditional imaging measure of AD pathology, and found the strongest negative correlations in AD patients between hippocampal volume and the diffusivities of the cingulum-angular and cingulum-cingulate gyrus bundles and of the corticospinal tracts (p<0.05). However, statistically controlling for hippocampal volume did not remove all group differences in white matter measures, suggesting a unique contribution of white matter damage to AD unexplained by this disease biomarker. These results suggest that (1) AD-associated deterioration of white matter fibers is greatest in tracts known to be connected to areas of pathology in AD and (2) lower white matter tract integrity is more diffusely associated with lower hippocampal volume indicating that the pathology in the white matter follows to some degree the neurodegenerative staging and progression of this condition.",Aged;Alzheimer Disease/ pathology;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Humans;Male;Mild Cognitive Impairment/pathology;White Matter/ pathology,"Lee, S. H.;Coutu, J. P.;Wilkens, P.;Yendiki, A.;Rosas, H. D.;Salat, D. H.",2015,Aug 20,10.1016/j.neuroscience.2015.05.049,0,
3013,Network degeneration and dysfunction in presymptomatic C9ORF72 expansion carriers,"Hexanucleotide repeat expansions in C9ORF72 are the most common known genetic cause of familial and sporadic frontotemporal dementia and amyotrophic lateral sclerosis. Previous work has shown that patients with behavioral variant frontotemporal dementia due to C9ORF72 show salience and sensorimotor network disruptions comparable to those seen in sporadic behavioral variant frontotemporal dementia, but it remains unknown how early in the lifespan these and other changes in brain structure and function arise. To gain insights into this question, we compared 15 presymptomatic carriers (age 43.7 +/- 10.2 years, nine females) to matched healthy controls. We used voxel-based morphometry to assess gray matter, diffusion tensor imaging to interrogate white matter tracts, and task-free functional MRI to probe the salience, sensorimotor, default mode, and medial pulvinar thalamus-seeded networks. We further used a retrospective chart review to ascertain psychiatric histories in carriers and their non-carrier family members. Carriers showed normal cognition and behavior despite gray matter volume and brain connectivity deficits that were apparent as early as the fourth decade of life. Gray matter volume deficits were topographically similar though less severe than those in patients with behavioral variant frontotemporal dementia due to C9ORF72, with major foci in cingulate, insula, thalamus, and striatum. Reduced white matter integrity was found in the corpus callosum, cingulum bundles, corticospinal tracts, uncinate fasciculi and inferior longitudinal fasciculi. Intrinsic connectivity deficits were detected in all four networks but most prominent in salience and medial pulvinar thalamus-seeded networks. Carrier and control groups showed comparable relationships between imaging metrics and age, suggesting that deficits emerge during early adulthood. Carriers and non-carrier family members had comparable lifetime histories of psychiatric symptoms. Taken together, the findings suggest that presymptomatic C9ORF72 expansion carriers exhibit functionally compensated brain volume and connectivity deficits that are similar, though less severe, to those reported during the symptomatic phase. The early adulthood emergence of these deficits suggests that they represent aberrant network patterning during development, an early neurodegeneration prodrome, or both.","ALS, amyotrophic lateral sclerosis;Amyotrophic lateral sclerosis;CDR, Clinical Dementia Rating scale;DMN, default mode network;Diffusion tensor imaging;FA, fractional anisotropy;FTD, frontotemporal dementia;FWE, familywise error;Frontotemporal dementia;Functional MRI;Genetics;HC, healthy control;ICN, intrinsic connectivity network;IRI, Interpersonal Reactivity Index;MMSE, Mini-Mental State Exam;MND, motor neuron disease;NPI, Neuropsychiatric Inventory;ROI, region of interest;SMN, sensorimotor network;TIV, total intracranial volume;VBM, voxel-based morphometry;bvFTD, behavioral variant frontotemporal dementia;fMRI, functional MRI;preSxC9, presymptomatic C9ORF72 expansion carriers","Lee, S. E.;Sias, A. C.;Mandelli, M. L.;Brown, J. A.;Brown, A. B.;Khazenzon, A. M.;Vidovszky, A. A.;Zanto, T. P.;Karydas, A. M.;Pribadi, M.;Dokuru, D.;Coppola, G.;Geschwind, D. H.;Rademakers, R.;Gorno-Tempini, M. L.;Rosen, H. J.;Miller, B. L.;Seeley, W. W.",2017,,,0,
3014,Prevalence and risk factors of silent cerebral infarction in apparently normal adults,"Cerebrovascular disease is a major cause of death and disability in adults. Silent cerebral infarction (SCI) portends more severe cerebral infarctions or may lead to insidious progressive brain damage resulting in vascular dementia. This study was designed to evaluate the prevalence and risk factors of SCI in an apparently normal adult population. Nine hundred ninety-four consecutive symptom-free adults (mean age 49.0+/-7.7; men:women 830:164) who underwent brain magnetic resonance imaging at the Center for Health Promotion at Samsung Medical Center were assessed. All were neurologically normal in history and physical examination. A total of 121 SCI lesions was observed in 58 subjects. The lesion prevalence adjusted for patient age was 5.1%. There was no gender difference in prevalence. Ninety-nine lesions were <1 cm in diameter, 15 were between 1 and 2 cm, 3 were between 2 and 3 cm, and 4 were >3 cm in diameter. The most frequent site of the SCI lesion was basal ganglia, after which the periventricular white matter, cerebral cortex, and thalamus were the most frequent sites. Old age, hypertension, a history of coronary artery disease, evidence of cardiomegaly in chest radiographs, and high fasting glucose/hemoglobin A1c levels were associated with SCI on univariate analysis. Multivariate analysis demonstrated old age and hypertension to be independent risk factors for SCI, and mild alcohol consumption was revealed as an independent protective factor against SCI.",Adult;Age Factors;Aged;Alcohol Drinking;Female;Humans;Male;Middle Aged;Multivariate Analysis;Myocardial Infarction/ epidemiology/etiology;Prevalence;Risk Factors,"Lee, S. C.;Park, S. J.;Ki, H. K.;Gwon, H. C.;Chung, C. S.;Byun, H. S.;Shin, K. J.;Shin, M. H.;Lee, W. R.",2000,Jul,,0,
3015,White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the Dominantly Inherited Alzheimer Network,"OBJECTIVE: White matter hyperintensities(WMH) are areas of increased signal on magnetic resonance imaging(MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease(AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically-determined to develop AD. METHODS: The study comprised participants(n=299, age=39.03+/-10.13) from the Dominantly Inherited Alzheimer Network, including 184(61.5%) with a mutation that results in AD and 115(38.5%) first-degree relatives who were non-carrier controls. We calculated the estimated years from expected symptom onset(EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed effects piecewise linear regression was used to examine WMH differences between carriers and non-carriers with respect to EYO. RESULTS: Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years prior to expected symptom onset. The effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years prior to estimated onset. INTERPRETATION: Autosomal dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMH are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. This article is protected by copyright. All rights reserved.",,"Lee, S.;Viqar, F.;Zimmerman, M. E.;Narkhede, A.;Tosto, G.;Benzinger, T. L.;Marcus, D. S.;Fagan, A. M.;Goate, A.;Fox, N. C.;Cairns, N. J.;Holtzman, D. M.;Buckles, V.;Ghetti, B.;McDade, E.;Martins, R. N.;Saykin, A. J.;Masters, C. L.;Ringman, J. M.;Ryan, N. S.;Frster, S.;Laske, C.;Schofield, P. R.;Sperling, R. A.;Salloway, S.;Correia, S.;Jack, C.;Weiner, M.;Bateman, R. J.;Morris, J. C.;Mayeux, R.;Brickman, A. M.",2016,Mar 26,10.1002/ana.24647,0,
3016,White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network,"OBJECTIVE: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD. We examined the severity and distribution of WMH in presymptomatic PSEN1, PSEN2, and APP mutation carriers to determine the extent to which WMH manifest in individuals genetically determined to develop AD. METHODS: The study comprised participants (n = 299; age = 39.03 +/- 10.13) from the Dominantly Inherited Alzheimer Network, including 184 (61.5%) with a mutation that results in AD and 115 (38.5%) first-degree relatives who were noncarrier controls. We calculated the estimated years from expected symptom onset (EYO) by subtracting the affected parent's symptom onset age from the participant's age. Baseline MRI data were analyzed for total and regional WMH. Mixed-effects piece-wise linear regression was used to examine WMH differences between carriers and noncarriers with respect to EYO. RESULTS: Mutation carriers had greater total WMH volumes, which appeared to increase approximately 6 years before expected symptom onset. Effects were most prominent for the parietal and occipital lobe, which showed divergent effects as early as 22 years before estimated onset. INTERPRETATION: Autosomal-dominant AD is associated with increased WMH well before expected symptom onset. The findings suggest the possibility that WMHs are a core feature of AD, a potential therapeutic target, and a factor that should be integrated into pathogenic models of the disease. Ann Neurol 2016;79:929-939.","0 (Amyloid beta-Peptides);0 (Amyloid beta-Protein Precursor);0 (Biomarkers);0 (MAPT protein, human);0 (PSEN1 protein, human);0 (PSEN2 protein, human);0 (Peptide Fragments);0 (Presenilin-1);0 (Presenilin-2);0 (amyloid beta-protein (1-42));0 (tau Proteins);Adult;Alzheimer Disease/cerebrospinal fluid/genetics/ pathology;Amyloid beta-Peptides/ cerebrospinal fluid;Amyloid beta-Protein Precursor/genetics;Biomarkers;Case-Control Studies;Female;Genetic Predisposition to Disease/genetics;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Neuroimaging;Peptide Fragments/ cerebrospinal fluid;Presenilin-1/genetics;Presenilin-2/genetics;White Matter/ pathology;Young Adult;tau Proteins/ cerebrospinal fluid","Lee, S.;Viqar, F.;Zimmerman, M. E.;Narkhede, A.;Tosto, G.;Benzinger, T. L.;Marcus, D. S.;Fagan, A. M.;Goate, A.;Fox, N. C.;Cairns, N. J.;Holtzman, D. M.;Buckles, V.;Ghetti, B.;McDade, E.;Martins, R. N.;Saykin, A. J.;Masters, C. L.;Ringman, J. M.;Ryan, N. S.;Forster, S.;Laske, C.;Schofield, P. R.;Sperling, R. A.;Salloway, S.;Correia, S.;Jack, C., Jr.;Weiner, M.;Bateman, R. J.;Morris, J. C.;Mayeux, R.;Brickman, A. M.;Dominantly Inherited Alzheimer, Network",2016,Jun,,0,
3017,A multi-center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysis,"Purpose: To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). Materials and Methods: Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. Results: A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. Conclusion: This is the first study to ascertain and validate the reliability and reproducibility of a short echo time 1HMRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting.",choline;creatine;inositol;n acetylaspartic acid;acquired immune deficiency syndrome;article;basal ganglion;brain level;controlled study;glia cell;human;Human immunodeficiency virus infection;major clinical study;metabolite;multicenter study;nerve cell;neuropathology;parietal lobe;phantom;priority journal;proton nuclear magnetic resonance;reliability;reproducibility;validation process;white matter,"Lee, P. L.;Yiannoutsos, C. T.;Ernst, T.;Chang, L.;Marra, C. M.;Jarvik, J. G.;Richards, T. L.;Kwok, E. W.;Kolson, D. L.;Simpson, D.;Tang, C. Y.;Schifitto, G.;Ketonen, L. M.;Meyerhoff, D. J.;Lenkinski, R. E.;Gonzalez, R. G.;Navia, B. A.",2003,,,0,
3018,Lymphomatosis cerebri: Diagnostic challenges and review of the literature,"Lymphomatosis cerebri (LC) is a rare variant of a primary central nervous system non-Hodgkin's lymphoma (PCNSL) characterised by diffuse infiltration of tumour cells throughout the brain parenchyma. We present a 68-year-old immunocompetent woman with headaches, dizziness, blurred vision, localised right leg weakness and rapidly progressive dementia. A brain MRI demonstrated diffuse T2 hyperintense white matter lesions that did not enhance with contrast. The clinical differential diagnosis of these lesions included metastatic disease, infectious or inflammatory process such as sarcoidosis, lymphoma, demyelinating disease and less likely vascular aetiology, such as vasculitis or ischaemic stroke. A right frontal stereotactic brain biopsy was non-diagnostic. The patient eventually died from aspiration pneumonia following a pneumonectomy for a primary lung adenocarcinoma. The diagnosis of LC was established on postmortem examination of the brain.",CD20 antigen;CD45 antigen;glial fibrillary acidic protein;methylprednisolone;protein bcl 2;aged;article;aspiration pneumonia;blurred vision;brain biopsy;brain ischemia;case report;dementia;demyelinating disease;differential diagnosis;dizziness;drug megadose;erythrocyte sedimentation rate;executive function;female;headache;human;human tissue;limb weakness;lung adenocarcinoma;lung resection;lymphoma;lymphomatosis;lymphomatosis cerebri;neuroimaging;nuclear magnetic resonance imaging;photophobia;priority journal;sarcoidosis;vasculitis,"Lee, P. J.;Berrios, I.;Ionete, C.;Smith, T.",2016,,10.1136/bcr-2016-216591,0,
3019,Synergistic effects of ischemia and beta-amyloid burden on cognitive decline in patients with subcortical vascular mild cognitive impairment,"IMPORTANCE: Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and beta-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins. OBJECTIVE: To determine the synergistic effects of beta-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI). DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes. MAIN OUTCOMES AND MEASURES: We measured beta-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment. RESULTS: On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI. CONCLUSIONS AND RELEVANCE: Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase beta-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.","Aged;Amyloid beta-Peptides/ metabolism;Brain/pathology;Brain Ischemia/ diagnosis/psychology;Cerebral Amyloid Angiopathy/ diagnosis/psychology;Comorbidity;Cross-Sectional Studies;Dementia, Vascular/ diagnosis/psychology;Disease Progression;Female;Humans;Image Interpretation, Computer-Assisted;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/psychology;Neuropsychological Tests;Positron-Emission Tomography;Prospective Studies;Statistics as Topic","Lee, M. J.;Seo, S. W.;Na, D. L.;Kim, C.;Park, J. H.;Kim, G. H.;Kim, C. H.;Noh, Y.;Cho, H.;Kim, H. J.;Yoon, C. W.;Ye, B. S.;Chin, J.;Jeon, S.;Lee, J. M.;Choe, Y. S.;Lee, K. H.;Kim, J. S.;Kim, S. T.;Lee, J. H.;Ewers, M.;Werring, D. J.;Weiner, M. W.",2014,Apr,10.1001/jamapsychiatry.2013.4506,0,
3020,Lower glomerular filtration rate associated with white matter hyperintensities more in vascular dementia than in Alzheimer's disease,,"Aged;Aging/*pathology;Alzheimer Disease/*pathology;Dementia, Vascular/*pathology;Female;*Glomerular Filtration Rate;Humans;*Magnetic Resonance Imaging;Male;Republic of Korea;Retrospective Studies;Risk Factors;White Matter/*pathology","Lee, K. S.;Na, D. L.;Seo, S. W.;Kim, J. H.;Choi, S. H.;Oh, B. H.;Son, S. J.;Hong, C. H.",2015,Jan,10.1111/jgs.13227,0,
3021,Form follows function: astrocyte morphology and immune dysfunction in SIV neuroAIDS,"Cortical function is disrupted in neuroinflammatory disorders, including HIV-associated neurocognitive disorders (HAND). Astrocyte dysfunction includes retraction of foot processes from the blood-brain barrier and decreased removal of neurotransmitters from synaptic clefts. Mechanisms of astrocyte activation, including innate immune function and the fine neuroanatomy of astrocytes, however, remain to be investigated. We quantified the number of glial fibrillary acidic protein (GFAP)-labeled astrocytes per square millimeter and the proportion of astrocytes immunopositive for Toll-like receptor 2 (TLR2) to examine innate immune activation in astrocytes. We also performed detailed morphometric analyses of gray and white matter astrocytes in the frontal and parietal lobes of rhesus macaques infected with simian immunodeficiency virus (SIV), both with and without encephalitis, an established model of AIDS neuropathogenesis. Protoplasmic astrocytes (gray matter) and fibrous astrocytes (deep white matter) were imaged, and morphometric features were analyzed using Neurolucida. Gray matter and white matter astrocytes showed no change in cell body size in animals infected with SIV regardless of encephalitic status. In SIV-infected macaques, both gray and white matter astrocytes had shorter, less ramified processes, resulting in decreased cell arbor compared with controls. SIV-infected macaques with encephalitis showed decreases in arbor length in white matter astrocytes and reduced complexity in gray matter astrocytes compared to controls. These results provide the first evidence that innate immune activation of astrocytes is linked to altered cortical astrocyte morphology in SIV/HIV infection. Here, we demonstrate that astrocyte remodeling is correlated with infection. Perturbed neuron-glia signaling may be a driving factor in the development of HAND.","AIDS Dementia Complex/immunology/pathology;Animals;Astrocytes/ immunology/ pathology;Disease Models, Animal;Fluorescent Antibody Technique;Macaca mulatta;Simian Acquired Immunodeficiency Syndrome/ immunology/ pathology","Lee, K. M.;Chiu, K. B.;Renner, N. A.;Sansing, H. A.;Didier, P. J.;MacLean, A. G.",2014,Oct,10.1007/s13365-014-0267-1,0,
3022,Different associations of white matter lesions with depression and cognition,"BACKGROUND: To test the hypothesis that white matter lesions (WML) are primarily associated with regional frontal cortical volumes, and to determine the mediating effects of these regional frontal cortices on the associations of WML with depressive symptoms and cognitive dysfunction. METHODS: Structural brains MRIs were performed on 161 participants: cognitively normal, cognitive impaired but not demented, and demented participants. Lobar WML volumes, regional frontal cortical volumes, depressive symptom severity, and cognitive abilities were measured. Multiple linear regression analyses were used to identify WML volume effects on frontal cortical volume. Structural equation modeling was used to determine the MRI-depression and the MRI-cognition path relationships. RESULTS: WML predicted frontal cortical volume, particularly in medial orbirtofrontal cortex, irrespective of age, gender, education, and group status. WML directly predicted depressive score, and this relationship was not mediated by regional frontal cortices. In contrast, the association between WML and cognitive function was indirect and mediated by regional frontal cortices. CONCLUSIONS: These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.","California/epidemiology;Cognition Disorders/*epidemiology/*pathology;Comorbidity;Depression/*epidemiology/*pathology;Female;Humans;Incidence;Magnetic Resonance Imaging/statistics & numerical data;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Reproducibility of Results;Risk Assessment;Risk Factors;Sensitivity and Specificity","Lee, J. Y.;Insel, P.;Mackin, R. S.;Schuff, N.;Chui, H.;DeCarli, C.;Park, K. H.;Mueller, S. G.;Weiner, M. W.",2012,,10.1186/1471-2377-12-83,0,
3023,"Delayed seizures and poor functional outcome after intracranial hemorrhage is the fate of patients with a poor underlying substrate, say the intensivists","Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants ε2/ε4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of ≥ 1 APOE ε4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.",anticonvulsive agent;article;brain hemorrhage;electroencephalogram;Glasgow coma scale;human;nuclear magnetic resonance imaging;seizure;x-ray computed tomography,"Lee, J. W.",2017,,10.5698/1535-7511.17.2.101,0,
3024,Diagonal Earlobe Crease is a Visible Sign for Cerebral Small Vessel Disease and Amyloid-beta,"We investigated the frequency and clinical significance of diagonal earlobe crease (DELC) in cognitively impaired patients using imaging biomarkers, such as white matter hyperintensities (WMH) on MRI and amyloid-beta (Abeta) PET. A total of 471 cognitively impaired patients and 243 cognitively normal (CN) individuals were included in this study. Compared with CN individuals, cognitively impaired patients had a greater frequency of DELC (OR 1.6, 95% CI 1.1-2.2, P = 0.007). This relationship was more prominent in patients with dementia (OR 1.8, 95% CI 1.2-2.7, P = 0.002) and subcortical vascular cognitive impairment (OR 2.4, 95% CI 1.6-3.6, P < 0.001). Compared with Abeta-negative cognitively impaired patients with minimal WMH, Abeta-positive patients with moderate to severe WMH were significantly more likely to exhibit DELC (OR 7.3, 95% CI 3.4-16.0, P < 0.001). We suggest that DELC can serve as a useful supportive sign, not only for the presence of cognitive impairment, but also for cerebral small vessel disease (CSVD) and Abeta-positivity. The relationship between DELC and Abeta-positivity might be explained by the causative role of CSVD in Abeta accumulation.",,"Lee, J. S.;Park, S.;Kim, H. J.;Kim, Y.;Jang, H.;Kim, K. W.;Rhee, H. Y.;Yoon, S. S.;Hwang, K. J.;Park, K. C.;Moon, S. H.;Kim, S. T.;Lockhart, S. N.;Na, D. L.;Seo, S. W.",2017,Oct 17,,0,
3025,"Cerebral microbleeds, hypertension, and intracerebral hemorrhage in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy","Background: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of stroke. In addition to ischemic stroke, CADASIL predisposes to development of cerebral microbleeds (CMB). CMB and hypertension are known to be associated with intracerebral hemorrhage (ICH). The purpose of this study was to analyze the relationships among CMB, hypertension, and ICH in CADASIL. Materials and methods: We enrolled 94 genetically confirmed CADASIL patients from 76 unrelated families at Jeju National University Hospital (Korea) between March 2012 and February 2015. We analyzed CMB presence, number, and distribution on susceptibility-weighted imaging MRI using the microbleed anatomical rating scale. Multiple logistic regression was used to determine factors associated with the presence of CMB and ICH. Results: CMB were observed in 62 patients (66%), median number of CMB per patient was 4 (range 0-121). Twenty-two ICHs were found in 16 patients (17%). There was incongruence between the most common site of CMB (thalamus) and that of ICH (basal ganglia). Hypertension was independently associated with the presence of CMB (multiple regression OR, 2.71; 95% CI 1.02-7.18, p < 0.05), and CMB = 9 (highest third) was significantly associated with the presence of ICH (multiple regression OR = 9.50, 95% CI 1.08-83.71, p < 0.05). Conclusion: In this CADASIL sample, presence of hypertension was independently associated with CMB presence, and CMB burden was independently associated with ICH. Incongruence of sites for CMB and ICH is currently unexplained and requires further study.",adult;aged;article;basal ganglion;brain hemorrhage;CADASIL;disease association;female;human;hypertension;Korea;major clinical study;male;neuroimaging;nuclear magnetic resonance scanner;psychological rating scale;risk factor;susceptibility weighted imaging;thalamus;university hospital;Achieva,"Lee, J. S.;Ko, K.;Oh, J. H.;Park, J. H.;Lee, H. K.;Floriolli, D.;Paganini-Hill, A.;Fisher, M.",2017,,10.3389/fneur.2017.00203,0,
3026,Coronary artery calcium is associated with cortical thinning in cognitively normal individuals,"To evaluate the association between coronary artery calcium (CAC) and cortical thickness in a large sample of cognitively normal individuals, with special emphasis in determining if the association thickness has regional brain specificity and if it is mediated by white matter hyperintensities (WMH). A total of 512 participants were included in this study. CAC scores were assessed by multi-detector computed tomography. Cortical thickness was measured using a surface-based method. Linear mixed models were used to assess the association between CAC scores and cortical thickness. In fully adjusted models, increased CAC scores were associated with cortical thinning across several brain regions, which generally overlapped with the distribution of default mode network. The association between CAC scores and cortical thickness was significantly stronger in participants with moderate or severe WMH compared to those with none or mild WMH, even though CAC scores were not associated with WMH. In cognitively normal adults, CAC was associated with cortical thinning in areas related to cognitive function. This association was evident after adjusting for multiple coronary artery disease risk factors and for WMH, suggesting that CAC may be more closely related to Alzheimer's Disease-type disease rather than to cerebral small vessel disease.",,"Lee, J. S.;Kang, D.;Jang, Y. K.;Kim, H. J.;Na, D. L.;Shin, H. Y.;Kang, M.;Yang, J. J.;Lee, J. M.;Lee, J.;Kim, Y. J.;Park, K. C.;Guallar, E.;Seo, S. W.;Cho, J.",2016,Oct 03,,0,
3027,Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation,"BACKGROUND AND PURPOSE: Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single-gene disorder of cerebral small blood vessels caused by NOTCH3 mutations, little has been described about the variation in the clinical findings between its underlying types of mutations. In particular, the presence of cerebral microbleeds (CMBs) has been an increasingly recognized magnetic resonance imaging finding in CADASIL, but their clinical significance is not clear. The purpose of this study is to assess whether CMBs are associated with symptomatic stroke in the CADASIL patients with R544C mutation and to compare the cerebral distribution of CMBs between CADASIL patients with and without symptomatic stroke. METHODS: This is a cohort study of patients who were diagnosed with genotype-confirmed R544C-mutation CADASIL. Primary neurologic symptoms were recorded. Symptomatic strokes were defined as transient ischemic attack, ischemic strokes and hemorrhagic strokes. CMBs were defined as focal areas of round signal loss on T2*-weighted gradient echo planar images with a diameter of less than 10 mm. The locations of CMBs were divided into lobar, basal ganglia, thalamus, brain stem and cerebellum. Multiple logistic regressions were performed to identify the epidemiologic or vascular risk factors associated with symptomatic stroke in patients with CADASIL. RESULTS: Among total of 51 subjects in this cohort, CMBs were present in 20 of 32 patients (64.5%) in the symptomatic stroke-group and in 8 of 19 patients (42.1%) in the non-stroke group (p = 0.16). CMBs were observed more frequently in the basal ganglia (p<0.001) and the cerebellum (p<0.018) in the symptomatic stoke group compared to the non-stroke group. The mean number of CMBs was significantly higher in the symptomatic stroke group (15.4+/-18.0 lesions per patients with CMBs) versus those without symptomatic stroke (3.3+/-3.0 lesions per patients with CMBs) (p = 0.003). Hypertension was an independent risk factor for symptomatic stroke in CADASIL (p = 0.014). It was independently associated with CMBs locations as basal ganglia (p = 0.016), thalamus (p = 0.010), brainstem (p = 0.044), and cerebellum (p = 0.049). However, It was not independently associated with CMBs on lobar lesion (p = 0.152). CONCLUSIONS: In this study hypertension was an independent predictor of CMBs presence in specific brain locations, as well as symptomatic stroke in the CADASIL patients. The distribution and burden of CMBs might be a clinically useful marker for the risk of symptomatic stroke. However, further prospective studies on the relationship between CMBs distribution and symptomatic stroke are required in order to support these preliminary findings.","Adult;Aged;Aged, 80 and over;Basal Ganglia/pathology;CADASIL/ complications/ genetics/pathology;Cerebellum/pathology;Cerebral Hemorrhage/genetics/ pathology;Female;Humans;Hypertension/epidemiology;Logistic Models;Male;Middle Aged;Mutation;Prospective Studies;Receptors, Notch/genetics;Risk Factors;Stroke/ pathology","Lee, J. S.;Kang, C. H.;Park, S. Q.;Choi, H. A.;Sim, K. B.",2015,,10.1371/journal.pone.0118163,0,
3028,Effects of lacunar infarctions on cognitive impairment in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL. METHODS: We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)]. RESULTS: A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis. CONCLUSIONS: These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.",cerebral autosomal-dominant arteriopathy with subcortical infarcts and;leukoencephalopathy;cerebral microbleeds;lacunes;white-matter hyperintensities,"Lee, J. S.;Choi, J. C.;Kang, S. Y.;Kang, J. H.;Na, H. R.;Park, J. K.",2011,Dec,10.3988/jcn.2011.7.4.210,0,
3029,Olfactory identification deficits in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND/AIMS: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited angiopathy caused by mutations of the Notch 3 gene. Olfactory identification deficits are present in a number of neurodegenerative disorders. However, olfaction has not been investigated in CADASIL. The aim of the present study was to assess olfactory identification in CADASIL and to determine whether there is an association between olfactory identification and the frontotemporal lobe. METHODS: Twenty-seven patients and 27 control subjects had an olfactory identification test and neuropsychological testing. Brain MRIs were obtained from 25 patients. Involvement of frontal white matter, anterior temporal white matter and the external capsule were measured. RESULTS: Olfactory identification scores were lower in CADASIL patients than in healthy comparison subjects. The Mini-Mental Status Examination (MMSE) and semantic Controlled Oral Word Association Test (COWAT) were also affected. In CADASIL patients, olfactory identification scores correlated with MMSE, COWAT scores and Scheltens' scores from frontal white matter. The tendency for an association between olfactory identification scores and Scheltens' scores from anterior temporal white matter was also observed. CONCLUSION: Our findings suggest that olfactory identification deficits may be a sensitive indicator of frontotemporal dysfunction in CADASIL.",Adult;Aged;Brain/pathology;CADASIL/*complications;Female;Humans;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Olfaction Disorders/diagnosis/*etiology,"Lee, J. S.;Choi, J. C.;Kang, S. Y.;Kang, J. H.;Lee, S. H.;Kim, J. H.;Kim, S.",2010,,10.1159/000320942,0,
3030,Impact of White Matter Lesions on Depression in the Patients with Alzheimer's Disease,"OBJECTIVE: Comorbid depression is common in patients with Alzheimer's disease (AD). An increase in white matter lesions (WMLs) has been associated with depression in both elderly individuals with normal cognition and patients with Alzheimer's disease. We investigated whether the severity and location of WMLs influence the association between WMLs and comorbid depression in AD. METHODS: We enrolled 93 AD patients from Seoul National University Bundang Hospital. We administered both the Mini International Neuropsychiatric Inventory (MINI) and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) clinical and neuropsychological battery. Subjects also underwent brain magnetic resonance imaging (MRI). We diagnosed AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We diagnosed depressive disorders according to the DSM-IV diagnostic criteria, and evaluated the severity of depressive symptoms using the Korean version of the Geriatric Depression Scale (GDS-K). We quantified the WML volumes from the brain MRI using a fully automated segmentation algorithm. RESULTS: The log of the WML volume in the frontal lobe was significantly associated with depressive disorders (odds ratio=1.905, 95% CI=1.027-3.533, p=0.041), but not with the severity of depressive symptoms as measured by the GDS-K. CONCLUSION: The WML volume in the frontal lobe conferred a risk of comorbid depressive disorders in AD, which implies that comorbid depression in AD may be attributed to vascular causes.",,"Lee, J. J.;Lee, E. Y.;Lee, S. B.;Park, J. H.;Kim, T. H.;Jeong, H. G.;Kim, J. H.;Han, J. W.;Kim, K. W.",2015,Oct,10.4306/pi.2015.12.4.516,0,
3031,Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B,"BACKGROUND: Subcortical vascular dementia (SVaD) is considered the most common type of vascular dementia and often follows a slowly progressive course, simulating Alzheimer disease (AD). Whether the progressive cognitive decline is associated with pure SVaD or concomitant AD remains unknown. The purpose of this study was to determine what proportion of patients with SVaD lack abnormal amyloid imaging, and to examine differences in the clinical or MRI features between subjects with SVaD with cortical amyloid deposition and those without. METHODS: We measured brain amyloid deposition using (11)C-Pittsburgh compound B (PiB) PET in 45 patients (men: women = 19:26; mean age 74.2 +/- 7.6 years) with SVaD. They all met DSM-IV criteria for vascular dementia and had severe white matter high signal intensities without territorial infarction or macrohemorrhage on MRI. RESULTS: Thirty-one (68.9%) of 45 patients with SVaD were negative for cortical PiB binding. There was significant difference between (11)C-PiB-positive and (11)C-PiB-negative groups in terms of age (79.5 vs 71.9 years), Mini-Mental State Examination score (18.6 vs 22.6), the number of lacunes (3.9 vs 9.0), and the visual rating scale of hippocampal atrophy (3.1 vs 2.3). The neuropsychological assessments revealed that patients with (11)C-PiB-negative SVaD performed better on the delayed recall of both the verbal and visual memory test than did those with (11)C-PiB-positive scan. CONCLUSION: SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.","Aged;Aged, 80 and over;Atrophy/pathology/radionuclide imaging;Benzothiazoles;Brain Mapping;Carbon Radioisotopes;Chi-Square Distribution;Dementia, Vascular/complications/pathology/ radionuclide imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Middle Aged;Movement Disorders/etiology;Neuropsychological Tests;Positron-Emission Tomography/methods;Psychiatric Status Rating Scales;Temporal Lobe/pathology/radionuclide imaging","Lee, J. H.;Kim, S. H.;Kim, G. H.;Seo, S. W.;Park, H. K.;Oh, S. J.;Kim, J. S.;Cheong, H. K.;Na, D. L.",2011,Jul 5,10.1212/WNL.0b013e318221acee,0,
3032,A comparative analysis of cognitive profiles and white-matter alterations using voxel-based diffusion tensor imaging between patients with Parkinson's disease dementia and dementia with Lewy bodies,"BACKGROUND: Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. METHODS: 19 patients with probable PDD and 18 patients with probable DLB who had a similar overall severity of dementia and demographic characteristics were examined by a standardised neuropsychological test and voxel-based analysis of fractional anisotropy (FA) using diffusion tensor imaging (DTI). RESULTS: The patients with DLB performed significantly worse in visual recognition memory, semantic fluency and ideomotor praxis than those with PDD (p<0.05). Compared with controls, the FA value in patients with PDD was significantly lower in bilateral frontal, left temporal and left parietal white matter. In patients with DLB, the pattern of FA reduction was similar to that of patients with PDD; however, white-matter abnormalities were more severe and extended into bilateral insular, bilateral posterior cingular and bilateral visual association regions. In a direct comparison between PDD and DLB, the FA value in patients with DLB was significantly decreased in bilateral posterior temporal, posterior cingular and bilateral visual association fibres extending into occipital areas. CONCLUSIONS: Despite global similarities in cognitive performance and white-matter pathology between DLB and PDD patients, those with DLB had more severely impaired frontal and temporal area-associated cognitive subsets, and more severe white-matter pathology in temporal and visual association fibres. These data suggest that differences in the underlying nature of PDD and DLB may exist with global similarities in their cognitive performance and white-matter pathology.","Aged;Aged, 80 and over;Cerebral Cortex/ pathology;Dementia/ diagnosis;Diagnosis, Differential;Diffusion Tensor Imaging;Dominance, Cerebral/physiology;Female;Gyrus Cinguli/ pathology;Humans;Lewy Body Disease/ diagnosis;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Parkinson Disease/ diagnosis","Lee, J. E.;Park, H. J.;Park, B.;Song, S. K.;Sohn, Y. H.;Lee, J. D.;Lee, P. H.",2010,Mar,10.1136/jnnp.2009.184747,0,
3033,A comparison of gray and white matter density in patients with Parkinson's disease dementia and dementia with Lewy bodies using voxel-based morphometry,"Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. We used voxel-based morphometry using a 3-T MRI scanner to compare gray and white matter densities in 20 patients with probable PDD and 18 patients with probable DLB, who had similar overall severity of dementia and similar demographic characteristics. The gray matter density was significantly decreased in the left occipital, parietal, and striatal areas in patients with DLB compared with patients with PDD. The white matter density was significantly decreased in bilateral occipital and left occipito-parietal areas in patients with DLB compared with those with PDD. The degree of white and gray matter atrophy was similar in patients with DLB; in contrast, there was markedly less atrophy in the white matter than in the gray matter in patients with PDD. On analyzing the change of WM density relative to that of GM density in patients with DLB compared to those with PDD, the area of WM atrophy in the occipital areas was more extensive than that of GM atrophy. Our data demonstrate that atrophy of both gray and white matter was more severe in patients with DLB and that white matter atrophy relative to gray matter atrophy was less severe in patients with PDD. These data may reflect a difference in the underlying nature of PDD and DLB.","Aged;Aged, 80 and over;Brain/*pathology;Female;Humans;Imaging, Three-Dimensional/methods;Lewy Body Disease/*pathology;Magnetic Resonance Imaging/methods;Male;Parkinson Disease/*pathology;Severity of Illness Index","Lee, J. E.;Park, B.;Song, S. K.;Sohn, Y. H.;Park, H. J.;Lee, P. H.",2010,Jan 15,10.1002/mds.22858,0,
3034,Longitudinal cortical thinning and cognitive decline in patients with early- versus late-stage subcortical vascular mild cognitive impairment,"BACKGROUND AND PURPOSE: Biomarker changes in cognitively impaired patients with small vessel disease are largely unknown. The rate of amyloid/lacune progression, cortical thinning and cognitive decline were evaluated in subcortical vascular mild cognitive impairment (svMCI) patients. METHODS: Seventy-two svMCI patients were divided into early stage (ES-svMCI, n = 39) and late stage (LS-svMCI, n = 33) according to their Clinical Dementia Rating Sum of Boxes score. Patients were annually followed up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and underwent a second [(11) C] Pittsburgh compound B (PiB) positron emission tomography scan within a mean interval of 32.4 months. RESULTS: There was no difference in the rate of increase in PiB uptake or lacune number between the ES-svMCI and LS-svMCI. However, LS-svMCI showed more rapid cortical thinning and cognitive decline than did the ES-svMCI. CONCLUSIONS: We suggest that, whilst the rate of change in pathological burden did not differ between ES-svMCI and LS-svMCI, cortical thinning and cognitive decline progressed more rapidly in the LS-svMCI.",cognition;cortical thickness;early stage;late stage;subcortical vascular mild cognitive impairment,"Lee, J.;Seo, S. W.;Yang, J. J.;Jang, Y. K.;Lee, J. S.;Kim, Y. J.;Chin, J.;Lee, J. M.;Kim, S. T.;Lee, K. H.;Lee, J. H.;Kim, J. S.;Kim, S.;Yoo, H.;Lee, A. Y.;Na, D. L.;Kim, H. J.",2018,Feb,,0,
3035,Late-onset vanishing white matter disease with compound heterozygous EIF2B5 gene mutations,,adult;ataxia;case report;dementia;depth perception;Diagnostic and Statistical Manual of Mental Disorders;female;gene mutation;human;letter;leukoencephalopathy;memory;Mini Mental State Examination;neurologic disease;neurologic examination;nuclear magnetic resonance imaging;priority journal;spasticity;vanishing white matter disease;white matter,"Lee, H. N.;Koh, S. H.;Lee, K. Y.;Ki, C. S.;Lee, Y. J.",2009,,,0,
3036,Amnestic multiple cognitive domains impairment and periventricular white matter hyperintensities are independently predictive factors progression to dementia in mild cognitive impairment,"Objective Mild cognitive impairment (MCI) usually represents a transitional phase between normal cognitive function and dementia, but not all people with MCI develop dementia because MCI is a clinically and etiologically heterogeneous grouping. The aim of this study was to determine whether clinical subtypes of MCI and severity of white matter hyperintensities (WMH) were associated with progression of MCI to dementia. Method Our study cohort consisted of 840 patients aged 55years or older who had a diagnosis of MCI at their baseline visit and had at least one follow-up contact after baseline. Results The results of the multivariable Cox proportional hazards model analysis revealed that both multiple domain amnestic MCI with WMH and multiple domain amnestic MCI without WMH were a significantly more likely to progress to dementia in comparison with patients with non-amnestic MCI. Logistic regression analyses showed that PWMH (periventricular white matter hyperintensities), not the deep white matter hyperintensities, was significantly associated with incident dementia. Conclusions This study showed that mdMCI+a (-NL or -WMH) are more associated with progression to dementia. We also found that increasing severity of PWMH, not deep white matter hyperintensities, was significantly associated with incident dementia, independently of subtype of MCI. It suggests that both mdMCI+a and PWMH are good prognostic factors of progression to dementia in MCI. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.",adult;aged;article;brain damage;brain disease;cohort analysis;controlled study;dementia;diagnostic test accuracy study;disease association;disease severity;female;follow up;human;incidence;logistic regression analysis;longitudinal study;major clinical study;male;middle aged;mild cognitive impairment;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;pathophysiology;periventricular white matter hyperintensity;predictive value;prognosis;proportional hazards model;risk factor;Stroop test;white matter;white matter hyperintensity,"Lee, H. K.;Lee, Y. M.;Park, J. M.;Lee, B. D.;Moon, E. S.;Chung, Y. I.",2014,,,0,
3037,Cerebral white matter disruption in Creutzfeldt-Jakob disease,"BACKGROUND AND PURPOSE: Human prion diseases are known to cause gray matter degeneration in specific cerebral structures, but evidence for white matter involvement is scarce. We used DTI to test the hypothesis that white matter integrity is disrupted in human CJD during the early stages of the disease. MATERIALS AND METHODS: Twenty-one patients with the E200K variant of CJD and 19 controls participated in DTI studies conducted on a 1.5T MR imaging scanner. The data were quantitatively analyzed and mapped with a voxelwise TBSS method. RESULTS: We found significant reductions of FA in patients with CJD in distinct and functionally relevant white matter pathways, including the corticospinal tract, internal capsule, external capsule, fornix, and posterior thalamic radiation. Moreover, these FA deficits increased with disease duration, and were mainly determined by increase of radial diffusivity, suggesting elevated permeability of axonal membranes. CONCLUSIONS: The findings suggest that some of the symptoms of CJD may be caused by a functional dysconnection syndrome, and that the leukoencephalopathy is progressive and detectable fairly early in the course of the disease.","Brain/ pathology;Creutzfeldt-Jakob Syndrome/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Lee, H.;Cohen, O. S.;Rosenmann, H.;Hoffmann, C.;Kingsley, P. B.;Korczyn, A. D.;Chapman, J.;Prohovnik, I.",2012,Nov,10.3174/ajnr.A3125,0,
3038,Depressive symptoms in mild cognitive impairment predict greater atrophy in alzheimer's disease-related regions,"Background: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. Methods: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. Results: Depressed subjects had more frontal (p =.024), parietal (p =.030), and temporal (p =.038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. Conclusions: Depressive symptoms were associated with greater atrophy in",,"Lee, G. J.;Lu, P. H.;Hua, X.;Lee, S.;Wu, S.;Nguyen, K.;Teng, E.;Leow, A. D.;Jack Jr, C. R.;Toga, A. W.;Weiner, M. W.;Bartzokis, G.;Thompson, P. M.",2012,1,,0,
3039,"Vascular and degenerative processes differentially affect regional interhemispheric connections in normal aging, mild cognitive impairment, and Alzheimer disease","BACKGROUND AND PURPOSE: Despite the critical importance of the corpus callosum (CC) to the connection between brain hemispheres, little is known about the independent contribution of degenerative and vascular processes to regional changes in the microstructural integrity of the CC. Here, we examine these changes in subjects with mild cognitive impairment, with Alzheimer disease, and in cognitively normal elderly adults. METHODS: We used 3-dimensional brain MRI with diffusion tensor imaging in 47 Alzheimer disease, 77 mild cognitive impairment, and 107 cognitively normal subjects, and we calculated mean fractional anisotropy (FA) values for 4 CC regions corresponding to 4 homologous regions of cortical gray matter (GM). To assess vascular and degenerative processes, we also measured cortical GM and white matter hyperintensity (WMH) volume in corresponding regions and evaluated their vascular risk. RESULTS: We found that GM volumes in anterior and posterior regions were significantly related to FA values in the corresponding regions of the CC for all 3 diagnostic groups. Independent of GM volume, frontal WMH volume was also associated with FA values in the corresponding CC regions, but posterior WMH volume was not. Vascular risk was associated with FA of most CC regions, whereas diagnosis of cognitive state was associated only with FA of the anterior and posterior CC regions. CONCLUSIONS: We found differential region-specific associations between degenerative and vascular processes and the structural integrity of the CC across the spectrum of cognitive ability. Based on these results, we propose a model to explain regional disruption in the interhemispheric connection.","Aged;Aged, 80 and over;Aging/ pathology/physiology;Alzheimer Disease/ pathology/physiopathology;Analysis of Variance;Anisotropy;Cerebrovascular Disorders/ pathology/physiopathology;Cognition Disorders/ pathology/physiopathology;Corpus Callosum/ pathology/physiopathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration/ pathology/physiopathology;Nerve Fibers, Myelinated/pathology;Risk Assessment","Lee, D. Y.;Fletcher, E.;Martinez, O.;Zozulya, N.;Kim, J.;Tran, J.;Buonocore, M.;Carmichael, O.;DeCarli, C.",2010,Aug,10.1161/strokeaha.110.582163,0,
3040,"Regional pattern of white matter microstructural changes in normal aging, MCI, and AD","OBJECTIVE: To cross-sectionally compare the regional white matter fractional anisotropy (FA) of cognitively normal (CN) older individuals and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), separately focusing on the normal-appearing white matter (NAWM) and white matter hyperintensities (WMH), and to test the independent effects of presumed degenerative and vascular process on FA differences. METHODS: Forty-seven patients with AD, 73 patients with MCI, and 95 CN subjects received diffusion tensor imaging and vascular risk evaluation. To properly control normal regional variability of FA, we divided cerebral white matter into 4 strata as measured from a series of young healthy individuals (H1 = highest; H2 = intermediate high; H3 = intermediate low; H4 = lowest anisotropy stratum). RESULTS: For overall cerebral white matter, patients with AD had significantly lower FA than CN individuals or patients with MCI in the regions with higher baseline anisotropy (H1, H2, and H3), corresponding to long corticocortical association fibers, but not in H4, which mostly includes heterogeneously oriented fibers. Vascular risk showed significant independent effects on FA in all strata except H1, which corresponds to the genu and splenium of the corpus callosum. Similar results were found within NAWM. FA in WMH was significantly lower than NAWM across all strata but was not associated with diagnosis or vascular risk. CONCLUSIONS: Both vascular and Alzheimer disease degenerative process contribute to microstructural injury of cerebral white matter across the spectrum of cognitive ability and have different region-specific injury patterns.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Analysis of Variance;Anisotropy;Brain/ pathology;Cognition Disorders/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Nerve Fibers, Myelinated/ pathology","Lee, D. Y.;Fletcher, E.;Martinez, O.;Ortega, M.;Zozulya, N.;Kim, J.;Tran, J.;Buonocore, M.;Carmichael, O.;DeCarli, C.",2009,Nov 24,10.1212/WNL.0b013e3181c33afb,0,
3041,Sub-Regional Hippocampal Injury is Associated with Fornix Degeneration in Alzheimer's Disease,"We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer's disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.",,"Lee, D. Y.;Fletcher, E.;Carmichael, O. T.;Singh, B.;Mungas, D.;Reed, B.;Martinez, O.;Buonocore, M. H.;Persianinova, M.;Decarli, C.",2012,,10.3389/fnagi.2012.00001,0,
3042,White matter changes associated with psychotic symptoms in Alzheimer's disease patients,"This study explored the relationship between white matter changes seen on magnetic resonance imaging (MRI) and neuropsychiatric symptoms of Alzheimer's disease patients. Fifty-five probable Alzheimer's disease patients were assessed with Behavioral Rating Scale for Dementia (BRSD) and MRI. White matter changes in the bilateral frontal or parieto-occipital region and left basal ganglia significantly corresponded with the score of the Psychotic Symptoms subscale of BRSD. Secondary analyses revealed that white matter changes were not associated with paranoid delusion and hallucination, but only with delusional misidentification. Our results suggest that white matter changes in Alzheimer's disease patients probably contribute to the development of specific psychotic symptoms, namely delusional misidentification.","Aged;Alzheimer Disease/ diagnosis/psychology;Basal Ganglia/pathology;Brain/ pathology;Capgras Syndrome/diagnosis/psychology;Cerebral Cortex/pathology;Delusions/diagnosis/psychology;Dominance, Cerebral/physiology;Female;Follow-Up Studies;Humans;Image Enhancement;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales;Psychotic Disorders/ diagnosis/psychology","Lee, D. Y.;Choo, I. H.;Kim, K. W.;Jhoo, J. H.;Youn, J. C.;Lee, U. Y.;Woo, J. I.",2006,Spring,10.1176/jnp.2006.18.2.191,0,
3043,Stereotypy after cerebellar infarction,,cilostazol;donepezil;fluorodeoxyglucose f 18;aged;case report;cerebellum infarction;Clinical Dementia Rating;cognitive defect;disorientation;female;follow up;frontal lobe;human;ideomotor apraxia;letter;medical history;memory disorder;motor dysfunction;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;positron emission tomography;priority journal;single photon emission computer tomography;stereotypy;verbal memory,"Lee, D.;Lee, D.;Ahn, T. B.",2014,,,0,
3044,Interobserver variation in computed tomography of the brain,"As part of the University of Western Ontario Dementia Study, the computed tomographic brain scans of 16 patients were reviewed by three neuroradiologists. The size of the ventricles and sulci were rated using a six-point scale. Infarction and white matter changes were assessed in accordance with specified criteria. The interobserver correlations in this small series were statistically significant in 17 of 20 items, and good or acceptable for infarction, leuko-araiosis, and ventricular size. It is suggested that the use of rigid criteria for the definition of abnormality helps to promote interobserver agreement.","Brain/pathology/*radiography;Brain Diseases/diagnosis;Humans;Myelin Sheath/*pathology;*Tomography, X-Ray Computed","Lee, D.;Fox, A.;Vinuela, F.;Pelz, D.;Lau, C.;Donald, A.;Merskey, H.",1987,Jan,,0,
3045,Effects of Homocysteine on white matter diffusion parameters in Alzheimer's disease,"BACKGROUND: The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores. METHODS: We enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor. RESULTS: The results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established. CONCLUSIONS: In our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations.",Alzheimer's disease;Default-mode network;Diffusion parameters;Homocysteine,"Lee, C. C.;Hsu, S. W.;Huang, C. W.;Chang, W. N.;Chen, S. F.;Wu, M. K.;Chang, C. C.;Hwang, L. C.;Chen, P. C.",2017,Oct 6,,0,
3046,Sicret-syndrome: A differential diagnosis of vasculitis and antiphospholipid syndrome,"Sicret-Syndrome (or Small Infarctions of Cochlear, Retinal and Encephalic Tissue) is rare. Its cause is unknown, but is often mistaken for vasculitis or antiphospholipid syndrome. This is a noninflammatory vasculopathy, who provokes infarcts exclusively in the cochlea, retina and brain of the young subjects, mostly women. Since 1973, about forty observations have been reported. 'Susac syndrome' is also commonly used, referred to the first author. Case report: a 25-year-old woman suffered, in June 1993, from vertigo and tinnitus, and from paresthesia of right upper limb and of the mouth with possible epileptic seizure. In September 1993, she had an abrupt loss of vision, caused by an occlusion of branch of the central retinal artery (right eye). There was observed an improvement of the retinal angiography after start treatment by prednisone 1 mg/kg/l and anticoagulation. But in october 1993, she had a second eye attack (left eye), despite the treatment by prednisone (30 mg). The physical examination showed increase deep tendon reflexes, a right extensor planter response and horizontal bilateral gaze nystagmus with unsteady gait. Brain MRI T2-weighted showed small multifocal hyperintensities in white matter but the intraarterial angiography was normal. Audiogramme disclosed neurosensory loss on low frequencies mostly in the left ear. Left vestibular caloric responses were diminished. The differential diagnosis particularly antiphospholipid syndrome and multiple sclerosis were remoted by multiple investigations. She was treated by oral corticoids, oral anticoagulation and sodium valproate since may 1995, when it relieve by low-dose aspirin. She had no new clinical manifestation. Retinal angiography is normalized, audiogram and brain MRI remain unchanged. In december 1998, she is still asymptomatic, except steady left hearing loss. In conclusion, this syndrome should be suspected in young women who suffer neurologic, auditory and ophthalmologic symptoms, but each feature of the triad can occur subclinical. Brain MRI, audiogram and vestibular tests, fundoscopy and fluorescein retinal angiography are very useful to confirm the diagnostic. There is full of differential diagnosises among them antiphospholipid syndrome and lupous erythematosus, Cogan syndrome and multiple sclerosis. Course is self-limited. Dementia, blindness and deafness are rare late sequelae. The treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy.",prednisone;adult;antiphospholipid syndrome;article;blindness;brain infarction;case report;dementia;differential diagnosis;female;human;Susac syndrome;vasculitis,"Leclair, A.;Limbach, F. X.;Javier, R. M.;Kuntz, J. L.;Sibilia, J.;Papo, Th",1999,,,0,
3047,[Hemorheology and H.E.L.P. in multi-infarct dementia] Hamorheologie und H.E.L.P. bei Multiinfarkt-Demenz,"Some papers report that the effect of heparin-mediated extracorporeal LDL less than cholesterol, LP(a), triglycerides, fibrinogen greater than precipitation (H.E.L.P.) in cardiovascular disease may results from an influence on the above-mentioned parameters. Hence, this method has been applied in multi-infarct dementia (MID), where fibrinogen, whole blood and plasma viscosity and red cell transit time (RCTT) are increased. The selection of patients was based on DMS-3, on NINCDS/ADRDA criteria and on the Hachinski Ischemic Stroke Scale. All the patients (n = 14) were examined magnet resonance imaging. Fibrinogen, cholesterol, LDL-cholesterol, HDL-cholesterol, LP(a), RCTT and plasma and whole blood viscosity were determined prior to, and after each two H.E.L.P. procedures. Fibrinogen was lowered (in a comparison of the data prior to the first and following the second plasmapheresis) from 526.4 +/- 114 to 314.1 +/- 80.1 mg/dl (p less than 0.01), cholesterol from 210.8 +/- 76.8 to 131.3 +/- 38.2 mg/dl (p less than 0.01), LDL from 125 +/- 53 mg/dl to 63.6 +/- 25.7 mg/dl (p less than 0.01), LP(a) from 26.2 +/- 13.2 to 12.0 +/- 9.5 mg/dl (p less than 0.01), HDL from 31.7 +/- 6.3 to 29.7 +/- 5.6 mg/dl (no significance), RCTT from 14.4 +/- 2.8 to 10.9 +/- 0.9 (p less than 0.01), whole blood viscosity (low shear rate) from 11.64 +/- 1.7 to 8.74 +/- 1.4 mPa/sec (p less than 0.01) and (high shear rate) from 5.38 +/- 0.58 to 4.28 +/- 0.83 mPa/sec (p less than 0.01). Plasma viscosity decreased from 1.51 +/- 0.12 mPa/sec to 1.25 +/- 0.1 mPa/sec (p less than 0.05). In cases of MID the implementation of H.E.L.P. therefore enabled an alteration of the hemorheological profile which has so far not been achieved by any hemorheologically active substance to a comparable degree and in comparable time.","0 (Cholesterol, LDL);0 (Lipoprotein(a));0 (Lipoproteins);0 (Lipoproteins, LDL);0 (Triglycerides);Aged;Blood Viscosity/ physiology;Chemical Precipitation;Cholesterol, LDL/ blood;Dementia, Multi-Infarct/blood/ therapy;Female;Hemofiltration/ instrumentation;Humans;Lipoprotein(a);Lipoproteins/ blood;Lipoproteins, LDL/ blood;Male;Middle Aged;Rheology;Triglycerides/ blood","Lechner, H.;Walzl, M.;Walzl, B.",1992,,,0,
3048,Hemorheology and H.E.L.P. in multi-infarct dementia,"Some papers report that the effect of heparin-mediated extracorporeal LDL less than cholesterol, LP(a), triglycerides, fibrinogen greater than precipitation (H.E.L.P.) in cardiovascular disease may results from an influence on the above-mentioned parameters. Hence, this method has been applied in multi-infarct dementia (MID), where fibrinogen, whole blood and plasma viscosity and red cell transit time (RCTT) are increased. The selection of patients was based on DMS-3, on NINCDS/ADRDA criteria and on the Hachinski Ischemic Stroke Scale. All the patients (n = 14) were examined magnet resonance imaging. Fibrinogen, cholesterol, LDL-cholesterol, HDL-cholesterol, LP(a), RCTT and plasma and whole blood viscosity were determined prior to, and after each two H.E.L.P. procedures. Fibrinogen was lowered (in a comparison of the data prior to the first and following the second plasmapheresis) from 526.4 +/- 114 to 314.1 +/- 80.1 mg/dl (p less than 0.01), cholesterol from 210.8 +/- 76.8 to 131.3 +/- 38.2 mg/dl (p less than 0.01), LDL from 125 +/- 53 mg/dl to 63.6 +/- 25.7 mg/dl (p less than 0.01), LP(a) from 26.2 +/- 13.2 to 12.0 +/- 9.5 mg/dl (p less than 0.01), HDL from 31.7 +/- 6.3 to 29.7 +/- 5.6 mg/dl (no significance), RCTT from 14.4 +/- 2.8 to 10.9 +/- 0.9 (p less than 0.01), whole blood viscosity (low shear rate) from 11.64 +/- 1.7 to 8.74 +/- 1.4 mPa/sec (p less than 0.01) and (high shear rate) from 5.38 +/- 0.58 to 4.28 +/- 0.83 mPa/sec (p less than 0.01). Plasma viscosity decreased from 1.51 +/- 0.12 mPa/sec to 1.25 +/- 0.1 mPa/sec (p less than 0.05). In cases of MID the implementation of H.E.L.P. therefore enabled an alteration of the hemorheological profile which has so far not been achieved by any hemorheologically active substance to a comparable degree and in comparable time.","Aged;Blood Viscosity/ physiology;Chemical Precipitation;Cholesterol, LDL/ blood;Dementia, Multi-Infarct/blood/ therapy;Female;Hemofiltration/ instrumentation;Humans;Lipoprotein(a);Lipoproteins/ blood;Lipoproteins, LDL/ blood;Male;Middle Aged;Rheology;Triglycerides/ blood","Lechner, H.;Walzl, M.;Walzl, B.",1992,,,0,
3049,Long-term experience of a trial in multi-infarct dementia,"A report is given on the natural history of multi-infarct dementia (MID) in 94 patients over a period of 5 years and describes neuroimaging criteria that may be used in order to more reliably separate vascular (VD) from primary degenerative types of dementia (DTD). The annual mortality rate of MID patients was 13%. Age and nocturnal confusion were found to be the most efficient predictors for fatal prognosis. Psychosocial adjustment, in contrast, indicated better outcome. In respect to differential diagnosis MRI revealed infarcts, basal ganglia lacunes and confluent white matter lesions as the most effective discriminators between VD and DTD. The typical patchy pattern found in almost half of the patients with VD, and significant differences in 5-7 Hz range as shown by EEG mapping can also be used for increasing the accuracy of the clinical diagnosis.",Aging;Alzheimer Disease/complications/psychology;Cerebrovascular Disorders/complications/physiopathology;Clinical Trials as Topic;Dementia/etiology/psychology/*therapy;Humans;Myocardial Infarction/*complications;Prospective Studies;Risk Factors,"Lechner, H.;Schmidt, R.;Goetz, B.",1990,,,0,
3050,Does cerebrovascular insufficiency contribute to Alzheimer's disease?,"The differential diagnosis of vascular dementia (VD) and Alzheimer's disease (AD) based on clinical assessment and neuropsychologic testing is still associated with a relatively high degree of inaccuracy compared to neuropathology standards. This is especially true in the identification of mixed forms between AD and VD. The present study investigates the potential of neuroimaging methods in providing additional information in dealing with this problem. Magnetic resonance imaging (MRI) of the brain identified a relatively high percentage (39%) of patients with AD (with ischemia scores of 4 and less) with basal ganglia hyperintensities and also demonstrated basal ganglia lacunae and infarcts in some of these patients. These findings indicate that in these cases a vascular component, consistent with the mixed form of dementia, may contribute to the etiology of the disease. These findings also underscore the clinical usefulness of MRI in the further differentiation of the dementias.","Aged;Alzheimer Disease/ diagnosis/physiopathology;Dementia, Vascular/ diagnosis/physiopathology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales","Lechner, H.;Niederkorn, K.;Schmidt, R.",1991,,,0,
3051,Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) revealed by Claude's syndrome,,Notch3 receptor;adult;CADASIL;case report;diplopia;dizziness;gene mutation;Horner syndrome;human;letter;male;neuroimaging;nuclear magnetic resonance imaging;ophthalmoplegia,"Le Doze, F.;Robert, M.;Apoil, M.;Wang, A.;Defer, G.",2012,,,0,
3052,"A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24","The majority of proximal myotonic myopathy syndromes reported so far have been related to the myotonic dystrophy (DM) type 2 (DM2) mutation, an expanded (CCTG)n repeat in the ZNF9 gene. Here, we describe the phenotype and the histological features in muscle and brain of the first large pedigree with a non-myotonic dystrophy type 1 (DM1) non-DM2 multisystem myotonic disorder associated with severe frontotemporal dementia. Thirty individuals from three generations underwent detailed neurological, neuropsychological, electrophysiological, brain imaging and molecular analyses. Ten of them had proximal muscle weakness at onset, clinical/electrical myotonia and DM-type cataracts. The mean age at onset was 46.7 +/- 12.6 years (range: 32-69). Dementia was observed later in the course of the disease. On muscle biopsies, rare nuclear clumps, rimmed vacuoles and small angulated type 1 and type 2 fibres were seen early in the disease. They were replaced by fibrous adipose tissue at later stages. Immunohistochemical analysis of myosin heavy chain isoforms showed no selective fibre type atrophy-both type 1 and type 2 fibres being affected. Cortical atrophy without white matter lesions was seen on brain MRI. A brain single photon emission computed tomography (SPECT) study revealed marked frontotemporal hypoperfusion. Post-mortem examination of the brains of two patients showing prominent frontotemporal spongiosis, neuronal loss and rare neuronal and glial tau inclusions suggested frontotemporal dementia. Western blot analyses of the tau protein showed a triplet of isoforms (60, 64 and 69 kDa) in neocortical areas, and a doublet (64 and 69 kDa) in subcortical areas that distinguish our myotonic disorder from other's myotonic dystrophies. Molecular analyses failed to detect a repeat expansion in the DMPK and ZNF9 genes excluding both DM1 and DM2, whereas a genome-wide linkage analysis strongly suggested a linkage to chromosome 15q21-24. This previously unreported multisystem myotonic disorder including findings resembling DM1, DM2 and frontotemporal dementia provides further evidence of the clinical and genetic heterogeneity of the myotonic dystrophies. We propose to designate this disease myotonic dystrophy type 3, DM3.","Adult;Age of Onset;Aged;Chromosome Mapping/methods;Chromosomes, Human, Pair 15/ genetics;Dementia/complications/ genetics/pathology;Female;Genetic Linkage/genetics;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Muscle Weakness/etiology/genetics/pathology;Muscle, Skeletal/pathology;Myosin Heavy Chains/analysis;Myotonic Disorders/complications/ genetics/pathology;Pedigree;Phenotype;RNA-Binding Proteins/genetics;Sex Ratio;tau Proteins/analysis","Le Ber, I.;Martinez, M.;Campion, D.;Laquerriere, A.;Betard, C.;Bassez, G.;Girard, C.;Saugier-Veber, P.;Raux, G.;Sergeant, N.;Magnier, P.;Maisonobe, T.;Eymard, B.;Duyckaerts, C.;Delacourte, A.;Frebourg, T.;Hannequin, D.",2004,Sep,10.1093/brain/awh216,0,
3053,Homozygous TREM2 mutation in a family with atypical frontotemporal dementia,"TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20-50years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. © 2014 Elsevier Inc.",,"Le Ber, I.;De Septenville, A.;Guerreiro, R.;Bras, J.;Camuzat, A.;Caroppo, P.;Lattante, S.;Couarch, P.;Kabashi, E.;Bouya-Ahmed, K.;Dubois, B.;Brice, A.",2014,October,,0,
3054,"A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb 761® in dementia","This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761® (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS- Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed. (C) 2000 S. Karger AG, Basel.",Ginkgo biloba extract;adult;aged;article;clinical trial;cognition;controlled clinical trial;controlled study;daily life activity;dementia;double blind procedure;drug efficacy;drug safety;female;human;major clinical study;male;multicenter study;priority journal;side effect;social behavior;egb 761,"Le Bars, P. L.;Kieser, M.;Itil, K. Z.",2000,,,0,
3055,The Dide-Botcazo syndrome: forgotten and misunderstood,"Bilateral infarcts of the posterior cerebral arteries are associated with a range of visual and memory deficits. In 1902, Dide and Botcazo presented a clinico-pathological case study linking visual field defects, topographical disorientation, retro-anterograde amnesia and alexia with bilateral medial occipito-temporal lesions. Based on the findings they suggested the occipital lobe and inferior longitudinal fasciculus played an important role in memory. The combination of deficits was subsequently referred to on occasion as Dide-Botcazo syndrome but the term was largely forgotten until revived in the 1980s. More recently, some authors have included visual anosognosia--Anton's syndrome--in the syndrome, a feature that was not in the original case report. Here we present a historical review of Dide-Botcazo syndrome, illustrated with a recent case with almost identical clinical features to that described by Dide and Botcazo. Although Dide and Botcazo's theory of occipital amnesia has been superseded by developments in our understanding of the neurobiology of memory, it seems fitting to remember in some way their description of a clinical association of visual and memory deficits. We suggest Dide-Botcazo syndrome be used to describe a variant of vascular dementia, where visual field deficits are associated with memory impairment and, depending on the location of the vascular lesions, visual perceptual dysfunction, topographic, imagery or dreaming deficits.","Aged;Agnosia/ diagnosis;Amnesia/diagnosis/ history;Blindness, Cortical/ diagnosis;Dyslexia/diagnosis/ history;Female;History, 20th Century;Humans;Occipital Lobe/ pathology;Syndrome","Lazzarino De Lorenzo, L. G.;Ffytche, D. H.;Di Camillo, E.;Buiatti, T.",2014,Jul,10.1016/j.cortex.2013.01.011,0,
3056,Metabolic brain mapping in Alzheimer's disease using proton magnetic resonance spectroscopy,"Alzheimer's disease (AD) is a progressive disorder associated with disruption of neuronal function and neuronal loss. N-acetylaspartate (NAA) is a marker of neuronal content and can be assessed using proton (1H) magnetic resonance spectroscopy (MRS). We utilized 1H-MRS (two-dimensional chemical-shift imaging) to assess amplitudes and areas of NAA, as well as choline moieties (Cho), creatine (Cr) and myo-inositol (mI), in 15 AD patients compared with 14 control subjects. Voxels were classified as predominantly cortical gray matter (CGM), subcortical gray matter (SGM), or white matter (WM). Compared with control subjects, AD patients exhibited decreased NAA/Cho and NAA/Cr amplitudes, whereas an increase was observed in Cho/Cr and in amplitude ratios involving mI. Area ratios were significant in the same direction for NAA/Cho, NAA/Cr, mI/Cr and mI/NAA. No significant effects of tissue type were observed; however, significant group x tissue type interactions were noted for Cho/Cr and mI/Cr amplitudes. Our study confirms that 1H-MRS can identify distinct physicochemical alterations in AD patients, reflecting membrane changes and diminished neuronal function. These alterations can be used as longitudinal markers for the disease.",Aged;Alzheimer Disease/ metabolism;Aspartic Acid/analogs & derivatives/metabolism;Brain/ metabolism;Brain Mapping;Choline/metabolism;Creatine/metabolism;Female;Humans;Inositol/metabolism;Magnetic Resonance Spectroscopy;Male,"Lazeyras, F.;Charles, H. C.;Tupler, L. A.;Erickson, R.;Boyko, O. B.;Krishnan, K. R.",1998,May 20,,0,
3057,White matter lesions on magnetic resonance imaging and their relationship with vascular risk factors in memory clinic attenders,"BACKGROUND: The association between white matter lesions on magnetic resonance imaging (MRI) and the presence of vascular risk factors has been investigated in different populations, and results have varied widely. However, this relationship has not been adequately addressed in memory clinic attenders who have relatively early cognitive impairment. OBJECTIVES: This study was undertaken to determine the relationship between the severity of white matter lesions and vascular risk factors in elderly subjects referred to a Memory Clinic, irrespective of their diagnoses. Patients attending the Memory Clinic had relatively early, mild cognitive impairment and differed, in this respect, from typical unselected community-based samples and from patients with established dementia. The study also investigated whether periventricular and deep white matter lesions differed in their relationship with vascular risk factors. METHODS: All patients assessed in the Memory Clinic at Leicester General Hospital between April 1998 and October 2000 who had undergone an MRI scan were included in the study. They received a comprehensive clinical and cognitive assessment, a standard dementia laboratory screen and evaluation of vascular risk factors. MRI scans were reviewed by two independent raters and semi-quantitative ratings of the severity of white matter lesions were made using standardised protocols. The relationship between cerebral white matter lesions and vascular risk factor variables was examined by multiple linear regression. RESULTS: One hundred and seventy-seven subjects were included in the study. The mean age was 69.8 and the mean MMSE score was 23.2. Of the risk factors investigated, only age and prior cerebrovascular disease were significantly associated with severe periventricular white matter lesions; age, hypertension and diabetes were significantly associated with severe deep white matter lesions. CONCLUSIONS: Periventricular and deep white matter lesions are differentially influenced by vascular risk factors.","Adult;Age Factors;Aged;Aged, 80 and over;Atrial Fibrillation/complications/pathology;Brain/ pathology;Cerebral Ventricles/pathology;Cerebrovascular Disorders/complications/pathology;Cognition Disorders/complications/ pathology;Diabetes Complications/pathology;Female;Humans;Hypertension/complications/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Myocardial Infarction/complications/pathology;Risk Factors","Lazarus, R.;Prettyman, R.;Cherryman, G.",2005,Mar,10.1002/gps.1283,0,
3058,Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging reveals cholesterol overload in the cerebral cortex of Alzheimer disease patients,"Although cholesterol has been involved in the pathophysiology of Alzheimer disease (AD), its distribution in the cerebral cortex over the course of AD is unknown. We describe an original method to quantify cholesterol distribution using time-of-flight secondary ion mass spectrometry imaging. Cholesterol was unevenly distributed along the cortical thickness, being more abundant close to the white matter, in both control and AD cases. However, the mean cholesterol signal was significantly higher in the lower half of the cortex in AD samples compared to controls. This increase, when converted into cortical layers, was statistically significant for layers III and IV and did not reach significance in layers V + VI, the variability being too high at the interface between grey and white matter. The density of neurofibrillary tangles and of senile plaques was not statistically linked to the abundance of cholesterol. Cholesterol overload thus appears a new and independent alteration of AD cerebral cortex. The structure in which cholesterol accumulates and the mechanism of this accumulation remain to be elucidated.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/pathology;Cerebral Cortex/ metabolism/pathology;Cholesterol/ metabolism;Female;Humans;Male;Middle Aged;Neurofibrillary Tangles/metabolism/ pathology;Neuroimaging;Plaque, Amyloid;Spectrometry, Mass, Secondary Ion/methods","Lazar, A. N.;Bich, C.;Panchal, M.;Desbenoit, N.;Petit, V. W.;Touboul, D.;Dauphinot, L.;Marquer, C.;Laprevote, O.;Brunelle, A.;Duyckaerts, C.",2013,Jan,10.1007/s00401-012-1041-1,0,
3059,Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study,"Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD. © 2013 Lawrence et al.",,"Lawrence, A. J.;Patel, B.;Morris, R. G.;MacKinnon, A. D.;Rich, P. M.;Barrick, T. R.;Markus, H. S.",2013,,,0,
3060,Structural network efficiency is associated with cognitive impairment in small-vessel disease,"Objective: To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. Methods: A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Results: Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Conclusions: Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. © 2014 American Academy of Neurology.",,"Lawrence, A. J.;Chung, A. W.;Morris, R. G.;Markus, H. S.;Barrick, T. R.",2014,22,,0,
3061,"The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia","OBJECTIVES: We examined the magnetic resonance imaging (MRI) correlates of depressed mood, apathy, anhedonia, and anergia in older adults with and without cognitive impairment or dementia. METHODS: This analysis included 270 community-dwelling older adults (59% male; 79% Caucasian; mean age 74.4 years) who were recruited into a multi-center longitudinal observational study of subcortical ischemic vascular disease (SIVD).The distribution of cognitive status included: cognitively intact (38%), cognitively impaired (27%), or demented (35%). All subjects underwent MRI and 41% were classified as having subcortical lacunes. MRI measures included cortical gray and white matter volumes, lacunar volumes in subcortical white and gray matter structures, volume of white matter hyperintensities, and total hippocampal volume. Depressed mood, anhedonia, anergia, and apathy apparent at the time of assessment were assessed using a behavioral assessment Associations between neuropsychiatric symptoms and MRI variables were evaluated using logistic regression. RESULTS: Subjects with neuropsychiatric symptoms were more likely to be cognitively impaired or demented than those without neuropsychiatric symptoms. In multivariate models controlling for cognitive status, age, gender, and education, higher lacunar volume in white matter was independently associated with the presence of all four neuropsychiatric symptoms. CONCLUSIONS: We report an association between the lacunar volumes in the white matter and depressed mood, anhedonia, apathy, and anergia, thus supporting the role of subcortical ischemic vascular disease in the pathogenesis of late-life neuropsychiatric disorders.",Age Factors;Aged;Brain/ pathology;Brain Ischemia/pathology;Cognition Disorders/ pathology;Dementia/ pathology;Depression/ pathology;Educational Status;Hippocampus/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Multivariate Analysis;Neuropsychological Tests;Sex Factors,"Lavretsky, H.;Zheng, L.;Weiner, M. W.;Mungas, D.;Reed, B.;Kramer, J. H.;Jagust, W.;Chui, H.;Mack, W. J.",2008,Oct,10.1002/gps.2030,0,
3062,Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease,"BACKGROUND AND PURPOSE: Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease. METHODS: Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations. RESULTS: At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries. CONCLUSIONS: We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.","Atorvastatin Calcium;Blood Pressure [drug effects];Brachial Artery [physiology];C-Reactive Protein [metabolism];Carotid Arteries [drug effects] [physiology];Cerebrovascular Circulation [physiology];Cerebrovascular Disorders [drug therapy] [pathology];Databases, Factual;Double-Blind Method;Endothelium, Vascular [drug effects] [physiology];Heptanoic Acids [administration & dosage] [therapeutic use];Hydroxymethylglutaryl-CoA Reductase Inhibitors [administration & dosage] [therapeutic use];Lipids [blood];Magnetic Resonance Imaging;Pyrroles [administration & dosage] [therapeutic use];Risk Factors;Stroke [drug therapy] [pathology];Treatment Outcome;Vasodilation [physiology];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Lavallée, P. C.;Labreuche, J.;Gongora-Rivera, F.;Jaramillo, A.;Brenner, D.;Klein, I. F.;Touboul, P. J.;Vicaut, E.;Amarenco, P.",2009,,,0,
3063,Delayed classic and protracted phenotypes of compound heterozygous juvenile neuronal ceroid lipofuscinosis,"Objective: To correlate the phenotypes with the genotypes of 10 Finnish juvenile neuronal ceroid lipofuscinosis (JNCL; late-onset Batten disease) patients who all are compound heterozygotes for the major 1.02-kb deletion in the CLN3 gene. Methods: The mutations on the non-1.02-kb deletion chromosomes were screened in 6 patients; in the other 4 patients the mutations were known (one affecting a splice site, two missense mutations, and one deletion of exons 10 through 13). Clinical features were examined, and MRI, MRS, somatosensory evoked magnetic field (SEF), and overnight polysomnography (PSG) studies were performed. Results: A novel deletion of exons 10 through 13 was found in 6 patients belonging to three families. In the patients carrying the deletions of exons 10 through 13 the clinical course of the disease was fairly similar. Variation was greatest in the time course to blindness. In these patients the mental and motor decline was slower than in classic JNCL, but more severe than in the two patients with missense mutations in exons 11 and 13. MRI showed brain atrophy in 4 patients. One patient had hyperintense periventricular white matter, otherwise brain signal intensities were normal. SEFs were enhanced in patients older than 14 years, whereas in PSG all but the youngest 6-year-old patient showed epileptiform activity in slow-wave sleep. Conclusions: JNCL can manifest as at least three different phenotypes: classic, delayed classic, and protracted JNCL with predominantly ocular symptoms. Finnish compound heterozygotes have the delayed classic or the protracted form of JNCL.",adolescent;adult;article;blindness;child;clinical article;controlled study;evoked somatosensory response;exon;female;Finland;gene deletion;genotype;heterozygosity;human;male;mental disease;missense mutation;motor dysfunction;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;nuclear magnetic resonance spectroscopy;phenotype;polysomnography;priority journal;white matter,"Lauronen, L.;Munroe, P. B.;Järvelä, I.;Autti, T.;Mitchison, H. M.;O'Rawe, A. M.;Gardiner, R. M.;Mole, S. E.;Puranen, J.;Häkkinen, A. M.;Kirveskari, E.;Santavuori, P.",1999,,,0,
3064,(99)Tc(m)-HMPAO SPECT in suspected dementia,"To evaluate the usefulness of (99)Tc(m)-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in suspected dementia we studied 160 consecutively imaged elderly patients from our hospital's memory disorder clinic. The diagnosis was based on clinical data, laboratory tests, neuropsychological examination, computed tomography (CT) and EEG. The patients were divided into six diagnostic categories: Alzheimer's disease (AD), multi-infarct dementia (MID), frontal lobe-type dementia (FTD), vascular encephalopathy not fulfilling the criteria of dementia, specific organic conditions, and psychiatric disorders. SPECT images were assessed without knowing the clinical diagnosis, and divided into AD pattern, FTD pattern, MID pattern, abnormal but unclassifiable, and normal. Twenty-three of 36 patients with clinical AD, 25/33 patients with clinical MID, and 2/5 patients with clinical TFD had compatible SPECT patterns. SPECT distinguished AD from MID in the majority (80%) of cases. In patients with depression or anxiety SPECT was abnormal in 16/21 cases, suggesting that SPECT may give early clues to the presence of an underlying organic disease in such elderly patients. Thus, SPECT with (99)Tc(m)-HMPAO seems to be useful in the diagnosis of suspected dementia.",,"Launes, J.;Sulkava, R.;Erkinjuntti, T.;Nikkinen, P.;Lindroth, L.;Liewendahl Iivanainen, K. M.",1991,1991,,0,
3065,"Medial temporal lobe atrophy in an open population of very old persons: Cognitive, brain atrophy, and sociomedical correlates","Medial temporal lobe structures may be important for memory. We examined the cognitive, brain atrophy, and sociomedical correlates of medial temporal lobe atrophy (MTA) in 59 individuals (79.2 ± 4.6 years old) randomly selected from a population-based study within strata of age and severity of clinically assessed DSM-III-R dementia (45 clinically normal and 14 mild/severely demented). MTA was qualitatively assessed on coronal T1- weighted MRI. Thirty-three percent of the sample showed MTA, which was associated with dementia severity (p < 0.01), and cortical and white matter atrophy. MTA was not associated with age, education, sex, depressive symptoms, or presence of infarction. Controlling for age, education, and associated brain atrophy, those with MTA performed more poorly on a general test of cognitive function (the neuropsychological test component of the Cambridge Examination for Mental Disorders of the Elderly; p < 0.04) and its subtests of memory function (p < 0.02) and memory-related functions, including perception, fluency, and orientation (p < 0.05). In the clinically normal subsample, those with MTA performed more poorly on the memory function (p < 0.05) subtests. We conclude that MTA is common among very old persons, is associated with other brain abnormalities implicated in cognitive function, but may specifically contribute to memory dysfunction in the general population of very old persons.",aged;amnesia;article;brain atrophy;cognition;controlled study;dementia;disease severity;female;human;major clinical study;male;neuropsychological test;nuclear magnetic resonance imaging;priority journal;temporal lobe;white matter,"Launer, L. J.;Scheltens, Ph;Lindeboom, J.;Barkhof, F.;Weinstein, H. C.;Jonker, C.",1995,,,0,
3066,CASCADE: a European collaborative study on vascular determinants of brain lesions. Study design and objectives,"Dementia is a highly prevalent disease that may have a cardiovascular component. White matter lesions and brain atrophy (brain abnormalities) are prevalent in dementia cases and might form part of the anatomical basis for the disease. We designed a multi-centre study, CASCADE (Cardiovascular Determinants of Dementia), to examine long-term (10-20 years) and short-term (5 years) cardiovascular risk factors for, and the cognitive consequence of, brain abnormalities. White matter lesions and atrophy are measured with magnetic resonance imaging. Cognitive function is measured with nine tests of memory and executive function. The studies included in CASCADE were ongoing and geographically spread throughout Europe to capture the cardiovascular risk gradient. In each study, a random sample of at least 100 subjects aged 65-75 years was selected who participated in the previous research examinations conducted by the respective centres. The objectives and design of the CASCADE project are described.",Aged;Cardiovascular Diseases/ complications;Dementia/ etiology;Europe;Humans;Risk Factors;Time Factors,"Launer, L. J.;Oudkerk, M.;Nilsson, L. G.;Alperovitch, A.;Berger, K.;Breteler, M. M.;Fuhrer, R.;Giampaoli, S.;Nissinen, A.;Pajak, A.;Sans, S.;Schmidt, R.;Hofman, A.",2000,May-Jun,26246,0,
3067,Vascular factors and multiple measures of early brain health: CARDIA brain MRI study,"OBJECTIVE: To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF). DESIGN: Cross-sectional brain Magnetic Resonance I (MRI) study. SETTING: Community based cohort in three U.S. sites. PARTICIPANTS: A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study. PRIMARY AND SECONDARY OUTCOMES: 3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function. RESULTS: Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01). CONCLUSION: In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.","Adolescent;Adult;Brain/blood supply/ pathology/ physiopathology;Cardiovascular Diseases/epidemiology/ pathology;Cognition;Cohort Studies;Cross-Sectional Studies;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;United States/epidemiology;Young Adult","Launer, L. J.;Lewis, C. E.;Schreiner, P. J.;Sidney, S.;Battapady, H.;Jacobs, D. R.;Lim, K. O.;D'Esposito, M.;Zhang, Q.;Reis, J.;Davatzikos, C.;Bryan, R. N.",2015,,10.1371/journal.pone.0122138,0,
3068,Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE),"White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions.","Aged/*physiology;Aging/physiology;Blood Pressure/physiology;Brain/*pathology;Brain Diseases/*epidemiology/*pathology;Cohort Studies;Education;Europe/epidemiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Risk Factors;Socioeconomic Factors","Launer, L. J.;Berger, K.;Breteler, M. M.;Dufouil, C.;Fuhrer, R.;Giampaoli, S.;Nilsson, L. G.;Pajak, A.;de Ridder, M.;van Dijk, E. J.;Sans, S.;Schmidt, R.;Hofman, A.",2006,,10.1159/000089233,0,
3069,"The role of prophylactic brain irradiation in limited stage small cell lung cancer: Clinical, neuropsychologic, and CT sequelae","Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of post-treatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated (rank correlation 0.7, p < .05). Overall, PBI after intensive combination chemotherapy did not induce gross dementia or neurologic dysfunction but its risk/benefit ratio is not overwhelmingly favorable, with failure to prevent brain relapse in 1/5 patients and subtle but detectable motor findings and neuropsychologic impairment in the majority.",cisplatin;cyclophosphamide;doxorubicin;etoposide;vincristine;adult;aged;arteriosclerosis;brain;brain disease;brain radiation;computer analysis;female;human;intravenous drug administration;lung carcinoma;major clinical study;male;neuropsychology;psychological aspect;radiation injury;radiotherapy;small cell carcinoma;adriamycin,"Laukkanen, E.;Klonoff, H.;Allan, B.;Graeb, D.;Murray, N.",1988,,,0,
3070,Microstructural White Matter Properties Mediate the Association between APOE and Perceptual Speed in Very Old Persons without Dementia,"BACKGROUND: Reduced white matter integrity, as indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD), has been related to poorer perceptual speed (PS) performance. As the epsilon4 allele has been associated with lower white matter integrity in old age, this represents a potential mechanism through which APOE may affect PS. OBJECTIVE: To examine whether the association between APOE and PS is mediated by white matter microstructure in very old persons without dementia. METHOD: Participants were selected from the population-based SNAC-K study. After excluding persons with dementia, preclinical dementia, and other neurological disorders, 652 persons (age range 78-90) were included in the study, of which 89 had data on diffusion tensor imaging (DTI). We used structural equation modeling to form seven latent white matter factors (FA and MD) and one latent PS factor. Separate analyses were performed for FA and MD and mediational analyses were carried out for tracts where significant associations were observed to both APOE and PS. RESULTS: APOE was associated with white matter microstructure in 2 out of 14 tracts; epsilon4 carriers had significantly lower FA in forceps major and higher MD in the cortico-spinal tract. Allowing the white matter microstructure indicators in these tracts to mediate the association between APOE and PS resulted in a markedly attenuated association between these variables. Bootstrapping statistics in the subsample with DTI data (n = 89) indicated that FA in forceps major significantly mediated the association between APOE and PS (indirect effect: -0.070, 95% bias corrected CIs -0.197 to -0.004). CONCLUSION: Lower white matter integrity may represent one of several mechanisms through which APOE affects PS performance in elderly persons free of dementia and preclinical dementia.",,"Laukka, E. J.;Lovden, M.;Kalpouzos, G.;Papenberg, G.;Keller, L.;Graff, C.;Li, T. Q.;Fratiglioni, L.;Backman, L.",2015,,10.1371/journal.pone.0134766,0,
3071,Associations between white matter microstructure and cognitive performance in old and very old age,"Increasing age is associated with deficits in a wide range of cognitive domains as well as with structural brain changes. Recent studies using diffusion tensor imaging (DTI) have shown that microstructural integrity of white matter is associated with cognitive performance in elderly persons, especially on tests that rely on perceptual speed. We used structural equation modeling to investigate associations between white matter microstructure and cognitive functions in a population-based sample of elderly persons (age >/= 60 years), free of dementia, stroke, and neurological disorders (n = 253). Participants underwent a magnetic resonance imaging scan, from which mean fractional anisotropy (FA) and mean diffusivity (MD) of seven white matter tracts were quantified. Cognitive functioning was analyzed according to performance in five task domains (perceptual speed, episodic memory, semantic memory, letter fluency, and category fluency). After controlling for age, FA and MD were exclusively related to perceptual speed. When further stratifying the sample into two age groups, the associations were reliable in the old-old (>/= 78 years) only. This relationship between white matter microstructure and perceptual speed remained significant after excluding persons in a preclinical dementia phase. The observed pattern of results suggests that microstructural white matter integrity may be especially important to perceptual speed among very old adults.","Aged;Aged, 80 and over;Brain/ ultrastructure;Cognition;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Laukka, E. J.;Lovden, M.;Kalpouzos, G.;Li, T. Q.;Jonsson, T.;Wahlund, L. O.;Fratiglioni, L.;Backman, L.",2013,,10.1371/journal.pone.0081419,0,
3072,HIV-related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times,"PURPOSE: To analyze brain metabolite changes in human immunodeficiency virus (HIV)-positive neurologically asymptomatic patients and patients with acquired immunodeficiency syndrome (AIDS) dementia complex (ADC). MATERIALS AND METHODS: Twelve ADC patients, 11 HIV-positive asymptomatic patients, and 10 healthy control subjects underwent magnetic resonance (MR) imaging and proton MR spectroscopy with short echo times. Changes in N-acetyl aspartate (NAA), choline (Cho), myoinositol (MI), and creatine (Cr) were presented as ratios with Cr as the reference. RESULTS: Statistically significant (P < .05) differences were noted. In ADC patients, all with MR findings of brain atrophy and diffuse white matter disease, NA/Cr decreased (white matter, -31.8%; gray matter, -22.3%), MI/Cr increased (white matter, +42.5%; gray matter, +51.8%), and Cho/Cr increased (white matter, +20.6%; gray matter, +51.7%) compared with healthy control subjects. In HIV-positive asymptomatic patients, NA/Cr decreased slightly (white matter, -6.9%; gray matter, -5.1%), MI/Cr increased slightly (white matter, +13.7%; gray matter, +10.7%), and Cho/Cr did not change. CONCLUSION: ADC has a uniform pathologic metabolic pattern that affects NAA, MI, and Cho. Proton MR spectroscopy with short echo times helps detect early abnormalities in clinically asymptomatic patients.",AIDS Dementia Complex/diagnosis/metabolism;Adult;Aged;Analysis of Variance;Brain/ metabolism;Female;Fourier Analysis;HIV Infections/diagnosis/ metabolism;Hiv-1;Humans;Magnetic Resonance Imaging/instrumentation/methods/statistics & numerical data;Magnetic Resonance Spectroscopy/instrumentation/ methods;Male;Middle Aged;Prospective Studies;Protons;Time Factors,"Laubenberger, J.;Haussinger, D.;Bayer, S.;Thielemann, S.;Schneider, B.;Mundinger, A.;Hennig, J.;Langer, M.",1996,Jun,10.1148/radiology.199.3.8638009,0,
3073,Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study,"OBJECTIVES: In patients with gout, maintaining too low serum uric acid (SUA) level with urate-lowering therapy is a concern because uric acid is thought to be neuroprotective. However, the relation between SUA and dementia remains debated. This study aimed to investigate the impact of SUA level on the incidence of dementia. METHODS: We assessed the longitudinal association between SUA level and incident dementia (Diagnostic and Statistical Manual of Mental Disorders Version IV (DSM-IV) criteria) in a large cohort of healthy older people from the community (Three-City Dijon cohort). Additionally, we investigated the relation between SUA level and MRI markers of brain ageing (white matter hyperintensity volume (WMHV), lacunes and hippocampal volume). RESULTS: The study sample comprised 1598 people (mean (SD) age 72.4(4.1) years, 38.3% male). During the 13,357 person-years of follow-up (median duration: 10.1 years), dementia developed in 110 participants (crude incidence rate: 8.2/1000 person-years). After multiple adjustments, the multivariate HR with the highest (>/=75th percentile) versus lowest SUA level was 1.79 (95% CI 1.17 to 2.73; p=0.007). The association was stronger with vascular or mixed dementia (HR=3.66 (95% CI 1.29 to 10.41), p=0.015) than Alzheimer's disease (HR=1.55 (95% CI 0.92 to 2.61), p=0.10). There was a non-significant trend towards an association between high SUA level and extensive WMHV (p=0.10), a biomarker of small vessel disease, but not hippocampal volume (p=0.94) or lacunes (p=0.86). The association between SUA level and vascular or mixed dementia might be affected by interim strokes. CONCLUSIONS: Risk of dementia, especially vascular or mixed dementia, may be increased with high SUA levels in elderly people.",cardiovascular disease;epidemiology;gout,"Latourte, A.;Soumare, A.;Bardin, T.;Perez-Ruiz, F.;Debette, S.;Richette, P.",2018,Mar,,0,
3074,"(99m)Tc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke: Report of a multicenter trial of 105 cases comparing (133)Xe and (99m)Tc-bicisate (ECD, neurolite) measured by SPECT on same day","A multicenter study was performed in seven European centers comparing (99m)Tc-bicisate with (133)Xe as a means of evaluating bicisate as a tracer of CBF distribution in humans. The same type of single photon emission computed tomography (SPECT) instrument (Tomomatic) was used in all centers. A total of 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between the results of the two methods was noted in 98 cases, but not in the remaining 7, all belonging to the stroke group. These seven all suffered from a subacute stroke (11-23 days after onset), and the disagreement in all cases consisted of bicisate showing low count rate in the area of the infarct and Xe a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute stroke cases does bicisate not follow CBF, as it fails to show reperfusion hyperemia. This suggests the usefulness of bicisate in stroke cases, particularly in the subacute phase, where other SPECT methods often present difficulties due to reflow masking the size and the severity of the lesion.",,"Lassen, N. A.;Sperling, B.",1994,1994,,0,
3075,Thomographic cerebral blood flow scanning in psychiatric diagnostics,"The paper summarises the role of tomographic cerebral blood flow SPECT scanning in psychiatric diagnostics, its' physical and radiopharmaceutical basis, pathological physiology of cerebrovascular circulation in psychiatric disorders and interpretation of cerebral blood flow scanning results by the clinician. Cerebral blood flow scanning is, to some extent, a functional equivalent of CT/MRI scanning. In psychiatry cerebral blood flow SPECT scanning's basic application is the differentiation of dementia and cognitive impairment, in particular Alzheimer's disease, frontotemporal lobar degeneration and multi-infarct dementia. The other indications for brain SPECT scanning involve the organic brain lesions and medico-legal diagnostics, including the sequelae of cranio-cerebral trauma. Contraindications and economical aspects are underlined.",Alzheimer disease;brain blood flow;brain circulation;brain degeneration;brain function;brain injury;cognitive defect;dementia;human;mental disease;multiinfarct dementia;patient monitoring;short survey;single photon emission computer tomography,"Lass, P.;Romanowicz, G.;Mizan, K.;Bandurski, T.;Afeltowicz, Z.;Lyczak, P.",1999,,,0,
3076,Cognitive impairment in patients with renal failure is associated with multiple-infarct dementia,"Purpose: Patients undergoing long-term renal replacement therapy (such as dialysis) have an increased risk for significant cognitive impairment, which may result in memory problems and subsequently missed attendance at dialysis. The aim of this study was to try to identify any abnormalities of cerebral perfusion that could explain a patient's cognitive impairment and to determine if the pattern of these abnormalities would suggest a cause. Materials and Methods: 17 patients (13 men; mean age, 60 years; age range, 29-74 years) in end-stage renal failure or on dialysis had SPECT imaging 10 minutes after injection of 550 MBq (15 mCi) Tc-99m HMPAO. Two of the patients had a history of previous stroke. Other risk factors for stroke were noted in most of the patients (hypertension in 10 patients, smoking or former smoking in 10 patients, and cardiac atherosclerosis in 7 patients). In all patients, attenuation correction was applied and the images were reconstructed into three sets of orthogonal slices. Activity in the frontal and temporal lobes was compared by quantification against the ipsilateral and contralateral cerebellum. Results: Discrete cortical defects consistent with infarcts were seen in 14 patients. The mean right and left frontal-to-cerebellar ratio was 0.837 (SD, 0.09) and 0.837 (SD, 0.08), respectively. This was not significantly different from the right and left temporal-to-cerebellar ratios of 0.843 (SD, 0.07) and 0.848 (SD, 0.07), respectively. Both were within normally accepted ranges. Conclusions: Patients in end-stage renal failure who also had cognitive impairment appear to have a high number of cortical defects consistent with infarcts (suggesting a multiple-infarct type of dementia). There was no evidence of Alzheimer-type dementia.",,"Lass, P.;Buscombe, J. R.;Harber, M.;Davenport, A.;Hilson, A. J. W.",1999,August,,0,
3077,"Magnetic resonance imaging and histopathology in dementia, clinically of frontotemporal type","The magnetic resonance imaging (MRI) and computed tomography findings in 28 patients with the clinical diagnosis of frontotemporal dementia (FTD) were compared with the findings in a control group of 76 individuals without dementia or stroke. A pattern of frontal and temporal atrophy with predominantly frontal white matter changes was found in the FTD patients, and this was significantly different from the radiological findings in the control group. Six of the FTD patients have undergone autopsy. Histopathological evaluation showed a primary cortical degenerative disease (frontal lobe degeneration of non-Alzheimer type) in 3 of them, and primary white matter disorder, mainly frontal, of basically ischemic type (selective incomplete white matter infarction) in 3 of them. MRI could be a helpful tool to support the clinical diagnosis FTD, especially in young patients. MRI may also be helpful for the differentiation of a primary neurodegenerative from a mainly ischemic-vascular type of dementia.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Atrophy/pathology;Cerebral Ventricles/pathology;Female;Frontal Lobe/ pathology/radiography;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Temporal Lobe/ pathology/radiography;Tomography, X-Ray Computed","Larsson, E.;Passant, U.;Sundgren, P. C.;Englund, E.;Brun, A.;Lindgren, A.;Gustafson, L.",2000,May-Jun,17225,0,
3078,[Tractography of the uncinate fasciculus and the posterior cingulate fasciculus in patients with mild cognitive impairment and Alzheimer disease] Tractografia del fasciculo uncinado y el fasciculo uncinado posterior en pacientes con deterioro cognitivo leve y enfermedad de Alzheimer,"INTRODUCTION: Brain tractography is a non-invasive medical imaging technique which enables in vivo visualisation and various types of quantitative studies of white matter fibre tracts connecting different parts of the brain. We completed a quantitative study using brain tractography with diffusion tensor imaging in patients with mild cognitive impairment, patients with Alzheimer disease, and normal controls, in order to analyse the reproducibility and validity of the results. SUBJECTS AND METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were measured across the uncinate fasciculus and the posterior cingulate fasciculus in images, obtained from a database and a research centre, representing 52 subjects distributed among the 3 study groups. Two observers took the measurements twice in order to evaluate intra- and inter-observer reproducibility. RESULTS: Measurements of FA and MD of the uncinate fasciculus delivered an intraclass correlation coefficient above 0.9; ICC was above 0.68 for the posterior cingulate fasciculus. Patients with Alzheimer disease showed lower values of FA and higher MD values in the right uncinate fasciculus in images from the research centre. A comparison of the measurements from the 2 centres revealed significant differences. CONCLUSION: We established a reproducible methodology for performing tractography of the tracts in question. FA and MD indexes may serve as early indicators of Alzheimer disease. The type of equipment and the method used to acquire images must be considered because they may alter results as shown by comparing the 2 data sets in this study.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Cognitive Dysfunction/ pathology;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Male;Middle Aged;Reproducibility of Results;Temporal Lobe/ pathology;Alzheimer disease;Demencia;Dementia;Deterioro cognitivo leve;Diffusion-weighted imaging;Enfermedad de Alzheimer;Imagen potenciada en difusion;Mild cognitive impairment;Sustancia blanca;Tractografia;Tractography;White matter","Larroza, A.;Moratal, D.;D'Ocon Alcaniz, V.;Arana, E.;por la Alzheimer's Disease Neuroimaging, Initiative",2014,Jan-Feb,,0,
3079,Tractography of the uncinate fasciculus and the posterior cingulate fasciculus in patients with mild cognitive impairment and Alzheimer disease,"INTRODUCTION: Brain tractography is a non-invasive medical imaging technique which enables in vivo visualisation and various types of quantitative studies of white matter fibre tracts connecting different parts of the brain. We completed a quantitative study using brain tractography with diffusion tensor imaging in patients with mild cognitive impairment, patients with Alzheimer disease, and normal controls, in order to analyse the reproducibility and validity of the results. SUBJECTS AND METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were measured across the uncinate fasciculus and the posterior cingulate fasciculus in images, obtained from a database and a research centre, representing 52 subjects distributed among the 3 study groups. Two observers took the measurements twice in order to evaluate intra- and inter-observer reproducibility. RESULTS: Measurements of FA and MD of the uncinate fasciculus delivered an intraclass correlation coefficient above 0.9; ICC was above 0.68 for the posterior cingulate fasciculus. Patients with Alzheimer disease showed lower values of FA and higher MD values in the right uncinate fasciculus in images from the research centre. A comparison of the measurements from the 2 centres revealed significant differences. CONCLUSION: We established a reproducible methodology for performing tractography of the tracts in question. FA and MD indexes may serve as early indicators of Alzheimer disease. The type of equipment and the method used to acquire images must be considered because they may alter results as shown by comparing the 2 data sets in this study.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Diffusion Tensor Imaging;Female;Gyrus Cinguli/ pathology;Humans;Male;Middle Aged;Mild Cognitive Impairment/ pathology;Reproducibility of Results;Temporal Lobe/ pathology","Larroza, A.;Moratal, D.;D'Ocon Alcaniz, V.;Arana, E.",2014,Jan-Feb,10.1016/j.nrl.2013.02.002,0,
3080,Clinical-anatomical correlation in a selective phonemic speech production impairment,"Although phonemic paraphasias are common in aphasic disorders, including Broca's aphasia, conduction aphasia and transcortical motor aphasia, selective phonemic speech production impairment, or phonemic disintegration, is unusual. A patient with a selective phonemic speech production disorder underwent clinical, neuropsychological and structural neuroradiological assessment over a period of 6 years. The disorder was characterised by phonemic paraphasias (phonemic disintegration) with preserved comprehension and naming. Imaging showed a focal lesion in the white matter of the left precentral gyrus and, to a lesser extent, the posterior part of the left middle frontal gyrus, with overlying cortical atrophy. Biopsy of the lesion, after several years of observation, showed a calcified haemangioma. Clinical-anatomical correlation in this case suggests the importance of primary motor cortex of the inferior precentral (pre-Rolandic) gyrus and subjacent white matter in phoneme production, with sparing of the posterior inferior frontal gyrus (Broca's area). © 2004 Elsevier B.V. All rights reserved.",,"Larner, A. J.;Robinson, G.;Kartsounis, L. D.;Rakshi, J. S.;Muqit, M. M. K.;Wise, R. J. S.;Cipolotti, L.;Rossor, M. N.",2004,15,,0,
3081,Spatz-Lindenberg disease: A rare cause of vascular dementia,"Background - Isolated cerebral thromboangiitis obliterans (Spatz- Lindenberg disease) is not well recognized as a cause of vascular dementia. Case Description - A 58-year-old woman presented with dementia and pyramidal signs. Neuroimaging showed multiple areas of white matter change. Brain biopsy showed intimal thickening of the walls of leptomeningeal and intraparenchymal arteries, almost to complete occlusion, with an intact internal elastic lamina and media and without inflammation or infiltration: The cortex showed only moderate gliosis. Conclusions - Spatz-Lindenberg disease should be considered in the differential diagnosis of vascular dementia. Additional studies of its pathogenesis are required to determine appropriate treatment.",adult;artery intima proliferation;article;brain biopsy;Buerger disease;case report;computer assisted tomography;differential diagnosis;female;gliosis;human;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;Spatz Lindenberg disease,"Larner, A. J.;Kidd, D.;Elkington, P.;Rudge, P.;Scaravilli, F.",1999,,,0,
3082,Osteoma of the calvaria in L-2-hydroxyglutaric aciduria,"L-2-Hydroxyglutaric aciduria (L-2-OHGA) is a rare autosomal recessive neurometabolic disease linked to chromosome 14q21.1 and is caused by mutations in the gene that most likely encodes L: -2-hydroxyglutarate dehydrogenase, which normally catalyses L: -2-hydroxyglutarate to alpha-ketoglutarate. It is characterized by progressive mental deterioration, pyramidal and cerebellar syndromes, macrocephaly and marked polycystic white-matter degeneration mainly involving frontal lobes. Brain tumours of variable nature have frequently been observed in L-2-OHGA. We report a patient affected by this disease who at the age of 20 years developed a bone tumour involving the right frontal region of the calvaria. He had first presented at the age of 10 years with psychomotor delay, clumsy gait and moderate mental impairment. Examination showed macrocephaly, cerebellar ataxia and quadripyramidal syndrome. Brain MRI showed low signal intensities on T1-weighted images and high signal intensities on T2-weighted images in cerebral subcortical white matter. Serum and urinary amino acid assay was normal. Urinary 2-hydroxyglutaric acid was 1418 mmol/mol creatinine (controls <25). Analysis of the L-2-hydroxyglutarate dehydrogenase gene revealed a homozygous mutation in exon 2 (A320G). At the age of 20 years, an osteoma of the right frontal bone was diagnosed. This finding reinforces the opinion concerning the association of L-2-OHGA and tumorigenesis and prompted us to verify the possible responsibility of some overproduced substances in this disease for the development of tumours and to look for any correlation between the type of mutation in the L-2-OHGA gene and the tumorigenic potential observed in some patients affected by this disease.",,"Larnaout, A.;Amouri, R.;Neji, S.;Zouari, M.;Kaabachi, N.;Hentati, F.",2007,Nov,,0,
3083,Apathy and impulsivity in frontotemporal lobar degeneration syndromes,"Apathy and impulsivity are common and disabling consequences of frontotemporal lobar degeneration. They cause substantial carer distress, but their aetiology remains elusive. There are critical limitations to previous studies in this area including (i) the assessment of either apathy or impulsivity alone, despite their frequent co-existence; (ii) the assessment of behavioural changes within single diagnostic groups; and (iii) the use of limited sets of tasks or questions that relate to just one aspect of these multifactorial constructs. We proposed an alternative, dimensional approach that spans behavioural and language variants of frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome. This accommodates the commonalities of apathy and impulsivity across disorders and reveals their cognitive and anatomical bases. The ability to measure the components of apathy and impulsivity and their associated neural correlates across diagnostic groups would provide better novel targets for pharmacological manipulations, and facilitate new treatment strategies and strengthen translational models. We therefore sought to determine the neurocognitive components of apathy and impulsivity in frontotemporal lobar degeneration syndromes. The frequency and characteristics of apathy and impulsivity were determined by neuropsychological and behavioural assessments in 149 patients and 50 controls from the PIck's disease and Progressive supranuclear palsy Prevalence and INcidence study (PiPPIN). We derived dimensions of apathy and impulsivity using principal component analysis and employed these in volumetric analyses of grey and white matter in a subset of 70 patients (progressive supranuclear palsy, n = 22; corticobasal syndrome, n = 13; behavioural variant, n = 14; primary progressive aphasias, n = 21) and 27 control subjects. Apathy and impulsivity were present across diagnostic groups, despite being criteria for behavioural variant frontotemporal dementia alone. Measures of apathy and impulsivity frequently loaded onto the same components reflecting their overlapping relationship. However, measures from objective tasks, patient-rated questionnaires and carer-rated questionnaires loaded onto separate components and revealed distinct neurobiology. Corticospinal tracts correlated with patients' self-ratings. In contrast, carer ratings correlated with atrophy in established networks for goal-directed behaviour, social cognition, motor control and vegetative functions, including frontostriatal circuits, orbital and temporal polar cortex, and the brainstem. Components reflecting response inhibition deficits correlated with focal frontal cortical atrophy. The dimensional approach to complex behavioural changes arising from frontotemporal lobar degeneration provides new insights into apathy and impulsivity, and the need for a joint therapeutic strategy against them. The separation of objective tests from subjective questionnaires, and patient from carer ratings, has important implications for clinical trial design.awx101media15448041163001.","Aged;Apathy/ physiology;Aphasia, Primary Progressive/diagnostic imaging/physiopathology;Female;Frontotemporal Dementia/diagnostic imaging/physiopathology;Frontotemporal Lobar Degeneration/ diagnostic imaging/ physiopathology;Gray Matter/ diagnostic imaging;Humans;Impulsive Behavior/ physiology;Magnetic Resonance Imaging;Male;Middle Aged;Pick Disease of the Brain/diagnostic imaging/physiopathology;Principal Component Analysis;Supranuclear Palsy, Progressive/diagnostic imaging/physiopathology;Syndrome;White Matter/ diagnostic imaging;apathy;frontotemporal lobar degeneration;impulsivity;voxel based morphometry","Lansdall, C. J.;Coyle-Gilchrist, I. T. S.;Jones, P. S.;Vazquez Rodriguez, P.;Wilcox, A.;Wehmann, E.;Dick, K. M.;Robbins, T. W.;Rowe, J. B.",2017,Jun 1,,0,
3084,Vascular dementia by thalamic strategic infarct,,adult;anatomy;apathy;article;attention deficit disorder;brain infarction;case report;clinical feature;electroencephalography;female;human;memory;memory disorder;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;single photon emission computer tomography;thalamus,"Lanna, M. E. D. O.;Madeira, D. M.;Alves, G.;Alves, C. E.;Valente, L. E.;Laks, J.;Engelhardt, E.",2008,,,0,
3085,White matter lesions relate to tract-specific reductions in functional connectivity,"White matter lesions play a role in cognitive decline and dementia. One presumed pathway is through disconnection of functional networks. Little is known about location-specific effects of lesions on functional connectivity. This study examined location-specific effects within anatomically-defined white matter tracts in 1584 participants of the Rotterdam Study, aged 50-95. Tracts were delineated from diffusion magnetic resonance images using probabilistic tractography. Lesions were segmented on fluid-attenuated inversion recovery images. Functional connectivity was defined across each tract on resting-state functional magnetic resonance images by using gray matter parcellations corresponding to the tract ends and calculating the correlation of the mean functional activity between the gray matter regions. A significant relationship between both local and brain-wide lesion load and tract-specific functional connectivity was found in several tracts using linear regressions, also after Bonferroni correction. Indirect connectivity analyses revealed that tract-specific functional connectivity is affected by lesions in several tracts simultaneously. These results suggest that local white matter lesions can decrease tract-specific functional connectivity, both in direct and indirect connections.",Brain;Connectivity;Function;Lesions;Location-specific,"Langen, C. D.;Zonneveld, H. I.;White, T.;Huizinga, W.;Cremers, L. G.;de Groot, M.;Ikram, M. A.;Niessen, W. J.;Vernooij, M. W.",2017,Mar,,0,
3086,Prediction of Alzheimer's Dementia in Patients with Amnestic Mild Cognitive Impairment in Clinical Routine: Incremental Value of Biomarkers of Neurodegeneration and Brain Amyloidosis Added Stepwise to Cognitive Status,"The aim of this study was to evaluate the incremental benefit of biomarkers for prediction of Alzheimer's disease dementia (ADD) in patients with mild cognitive impairment (MCI) when added stepwise in the order of their collection in clinical routine. The model started with cognitive status characterized by the ADAS-13 score. Hippocampus volume (HV), cerebrospinal fluid (CSF) phospho-tau (pTau), and the FDG t-sum score in an AD meta-region-of-interest were compared as neurodegeneration markers. CSF-Abeta1-42 was used as amyloidosis marker. The incremental prognostic benefit from these markers was assessed by stepwise Kaplan-Meier survival analysis in 402 ADNI MCI subjects. Predefined cutoffs were used to dichotomize patients as 'negative' or 'positive' for AD characteristic alteration with respect to each marker. Among the neurodegeneration markers, CSF-pTau provided the best incremental risk stratification when added to ADAS-13. FDG PET outperformed HV only in MCI subjects with relatively preserved cognition. Adding CSF-Abeta provided further risk stratification in pTau-positive subjects, independent of their cognitive status. Stepwise integration of biomarkers allows stepwise refinement of risk estimates for MCI-to-ADD progression. Incremental benefit strongly depends on the patient's status according to the preceding diagnostic steps. The stepwise Kaplan-Meier curves might be useful to optimize diagnostic workflow in individual patients.",Alzheimer's disease;Fdg;biomarker;cerebrospinal fluid;magnetic resonance imaging;mild cognitive impairment;neuropsychological testing;positron emission tomography;prediction;white matter hyperintensities,"Lange, C.;Suppa, P.;Pietrzyk, U.;Makowski, M. R.;Spies, L.;Peters, O.;Buchert, R.;Alzheimer's Disease Neuroimaging, Initiative",2018,,,0,
3087,Mental speed is associated with the shape irregularity of white matter MRI hyperintensity load,"Brain MRI white matter hyperintensities (WMHs) are common in elderly subjects. Their impact on cognition, however, appears highly variable. Complementing conventional scoring of WMH load (volume and location) by quantitative characterization of the shape irregularity of WMHs might improve the understanding of the relationship between WMH load and cognitive performance. Here we propose the ""confluency sum score"" (COSU) as a marker of the total shape irregularity of WMHs in the brain. The study included two independent patient samples: 87 cognitively impaired geriatric inpatients from a prospective neuroimaging study (iDSS) and 198 subjects from the National Alzheimer's Coordinating Center (NACC) database (132 with, 66 w/o cognitive impairment). After automatic segmentation and clustering of the WMHs on FLAIR (LST toolbox, SPM8), the confluency of the i-th contiguous WMH cluster was computed as confluencyi = [1/(36pi)surfacei(3)/volumei(2)](1/3)-1. The COSU was obtained by summing the confluency over all WMH clusters. COSU was tested for correlation with CERAD-plus subscores. Correlation analysis was restricted to subjects with at least moderate WMH load (>/= 13.5 ml; iDSS / NACC: n = 52 / 80). In the iDSS sample, among the 12 CERAD-plus subtests the trail making test A (TMT-A) was most strongly correlated with the COSU (Spearman rho = -0.345, p = 0.027). TMT-A performance was not associated with total WMH volume (rho = 0.147, p = 0.358). This finding was confirmed in the NACC sample (rho = -0.261, p = 0.023 versus rho = -0.040, p = 0.732). Cognitive performance in specific domains including mental speed and fluid abilities seems to be more strongly associated with the shape irregularity of white matter MRI hyperintensities than with their volume.",Biomarker;Cerad;Cerebrovascular disease;Confluency;Flair;Mri;White matter hyperintensities,"Lange, C.;Suppa, P.;Maurer, A.;Ritter, K.;Pietrzyk, U.;Steinhagen-Thiessen, E.;Fiebach, J. B.;Spies, L.;Buchert, R.",2017,Dec,,0,3088
3088,Mental speed is associated with the shape irregularity of white matter MRI hyperintensity load,"Brain MRI white matter hyperintensities (WMHs) are common in elderly subjects. Their impact on cognition, however, appears highly variable. Complementing conventional scoring of WMH load (volume and location) by quantitative characterization of the shape irregularity of WMHs might improve the understanding of the relationship between WMH load and cognitive performance. Here we propose the ""confluency sum score"" (COSU) as a marker of the total shape irregularity of WMHs in the brain. The study included two independent patient samples: 87 cognitively impaired geriatric inpatients from a prospective neuroimaging study (iDSS) and 198 subjects from the National Alzheimer's Coordinating Center (NACC) database (132 with, 66 w/o cognitive impairment). After automatic segmentation and clustering of the WMHs on FLAIR (LST toolbox, SPM8), the confluency of the i-th contiguous WMH cluster was computed as confluencyi = [1/(36pi)surfacei3/volumei2]1/3-1. The COSU was obtained by summing the confluency over all WMH clusters. COSU was tested for correlation with CERAD-plus subscores. Correlation analysis was restricted to subjects with at least moderate WMH load (>/= 13.5 ml; iDSS / NACC: n = 52 / 80). In the iDSS sample, among the 12 CERAD-plus subtests the trail making test A (TMT-A) was most strongly correlated with the COSU (Spearman rho = -0.345, p = 0.027). TMT-A performance was not associated with total WMH volume (rho = 0.147, p = 0.358). This finding was confirmed in the NACC sample (rho = -0.261, p = 0.023 versus rho = -0.040, p = 0.732). Cognitive performance in specific domains including mental speed and fluid abilities seems to be more strongly associated with the shape irregularity of white matter MRI hyperintensities than with their volume.",Biomarker;Cerad;Cerebrovascular disease;Confluency;Flair;Mri;White matter hyperintensities,"Lange, C.;Suppa, P.;Maurer, A.;Ritter, K.;Pietrzyk, U.;Steinhagen-Thiessen, E.;Fiebach, J. B.;Spies, L.;Buchert, R.",2016,Oct 28,,0,
3089,CT and MRI study of vascular cognitive impairment,"With the persisting development of the medical imaging technique, the neuroimaging has played more important role in diagnosis. In recent years, extensive attentions have been attracted on the CT and MRI technology study of vascular cognitive impairment (VCI). Research has found white matter changes and brain atropy were universal in VCI patients, and the severity and location of the changes which are closely related to the clinical manifestation of VCI patients. Therefore, this article will mainly discuss the CT and MRI findings in the investigation of VCI.",,"Lang, Y.;Jiang, C. B.;Yin, J.;Song, Y.",2011,20,,0,
3090,Characterization of multiple sclerosis plaques using susceptibility-weighted imaging at 1.5 T: can perivenular localization improve specificity of imaging criteria?,"BACKGROUND AND PURPOSE: The purpose of this study was to determine if magnetic resonance (MR) susceptibility-weighted imaging (SWI) can increase the conspicuity of corticomedullary veins within the white matter lesions of multiple sclerosis (MS) and, thus, aid in distinguishing plaques from leukoaraiosis. METHODS: We retrospectively reviewed MR examinations in 21 patients with a clinical diagnosis of MS and 18 patients with a clinical diagnosis of dementia. Examinations included fluid-attenuated inversion recovery (FLAIR) and SWI sequences obtained in the axial plane. Lesions greater than 5 mm in diameter on the axial FLAIR sequence were identified as periventricular or subcortical. Three neuroradiologists evaluated SWI images, compared with FLAIR, for a centrally located signal void in each lesion that was scored as present, absent, or indeterminate. RESULTS: In patients with MS, central veins were present in both periventricular lesions (75%, P < 0.001) and subcortical lesions (52%, P < 0.005). In patients with dementia, central veins were seen much less frequently in subcortical lesions (14%, P < 0.001); their association with periventricular lesions was not significant. CONCLUSIONS: Central veins were detected in MS lesions with a significantly greater frequency than that in patients with dementia. Susceptibility-weighted imaging increases the conspicuity of corticomedullary veins and may improve the specificity of MR findings in MS.","Aged;Cerebral Veins/ pathology;Cerebrovascular Disorders/ pathology;Dementia/ pathology;Diagnosis, Differential;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Image Interpretation, Computer-Assisted/methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Multiple Sclerosis/ pathology;Plaque, Atherosclerotic/ pathology;Reproducibility of Results;Retrospective Studies;Sensitivity and Specificity;White Matter/ pathology","Lane, J. I.;Bolster, B.;Campeau, N. G.;Welker, K. M.;Gilbertson, J. R.",2015,May-Jun,10.1097/rct.0000000000000233,0,
3091,Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers,"PURPOSE: The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers. METHODS: One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers. RESULTS: Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, rho = 0.84-0.99; PiB-florbetapir, rho = 0.83-0.97) and analysis method (rho = 0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs. CONCLUSION: Despite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.","Aged;Alzheimer Disease/ metabolism/ radionuclide imaging;Amyloid/ metabolism;Cerebral Cortex/metabolism/radionuclide imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Positron-Emission Tomography/ methods;Radiopharmaceuticals;White Matter/metabolism/radionuclide imaging","Landau, S. M.;Thomas, B. A.;Thurfjell, L.;Schmidt, M.;Margolin, R.;Mintun, M.;Pontecorvo, M.;Baker, S. L.;Jagust, W. J.",2014,Jul,10.1007/s00259-014-2753-3,0,
3092,Measurement of longitudinal β-amyloid change with <sup>18</sup>F-florbetapir PET and standardized uptake value ratios,"The accurate measurement of β-amyloid (Aβ) change using amyloid PET imaging is important for Alzheimer disease research and clinical trials but poses several unique challenges. In particular, reference region measurement instability may lead to spurious changes in cortical regions of interest. To optimize our ability to measure <sup>18</sup>F-florbetapir longitudinal change, we evaluated several candidate regions of interest and their influence on cortical florbetapir change over a 2-y period in participants from the Alzheimer Disease Neuroimaging Initiative (ADNI). Methods: We examined the agreement in cortical florbetapir change detected using 6 candidate reference regions (cerebellar gray matter, whole cerebellum, brain stem/pons, eroded subcortical white matter [WM], and 2 additional combinations of these regions) in 520 ADNI subjects. We used concurrent cerebrospinal fluid Aβ<inf>1-42</inf> measurements to identify subgroups of ADNI subjects expected to remain stable over follow-up (stable Aβgroup; n = 14) and subjects expected to increase (increasing Aβ group; n = 91). We then evaluated reference regions according to whether cortical change was minimal in the stable Aβgroup and cortical retention increased in the increasing Aβgroup. Results: There was poor agreement across reference regions in the amount of cortical change observed across all 520 ADNI subjects. Within the stable Aβ group, however, cortical florbetapir change was 1%- 2% across all reference regions, indicating high consistency. In the increasing Aβ group, cortical increases were significant with all reference regions. Reference regions containing WM (as opposed to cerebellum or pons) enabled detection of cortical change that was more physiologically plausible and more likely to increase over time. Conclusion: Reference region selection has an important influence on the detection of florbetapir change. Compared with cerebellum or pons alone, reference regions that included subcortical WM resulted in change measurements that are more accurate. In addition, because use of WM-containing reference regions involves dividing out cortical signal contained in the reference region (via partial-volume effects), use of these",,"Landau, S. M.;Fero, A.;Baker, S. L.;Koeppe, R.;Mintun, M.;Chen, K.;Reiman, E. M.;Jagust, W. J.",2015,1,,0,
3093,Diffusion Tensor Imaging Predictors of Episodic Memory Decline in Healthy Elders at Genetic Risk for Alzheimer's Disease,"OBJECTIVES: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer's disease (AD). METHODS: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E epsilon4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1-5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors. RESULTS: Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both epsilon4 status and DTI correlated with change in immediate recall. CONCLUSIONS: Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005-1015).",Alzheimer's disease;Anatomical MRI;Apolipoprotein E;Diffusion tensor imaging;Episodic memory;Mesial temporal lobe,"Lancaster, M. A.;Seidenberg, M.;Smith, J. C.;Nielson, K. A.;Woodard, J. L.;Durgerian, S.;Rao, S. M.",2016,Nov,,0,
3094,Fetal-type variants of the posterior cerebral artery and concurrent infarction in the major arterial territories of the cerebral hemisphere,"Fetal-type or fetal posterior cerebral artery (FPCA) is a variant of cerebrovascular anatomy in which the distal posterior cerebral artery (PCA) territory is perfused by a branch of the internal carotid artery (ICA). In the presence of FPCA, thromboembolism in the anterior circulation may result in paradoxical PCA territory infarction with or without concomitant infarction in the territories of the middle (MCA) or the anterior (ACA) cerebral artery. We describe 2 cases of FPCA and concurrent acute infarction in the PCA and ICA territories—right PCA and MCA in Patient 1 and left PCA, MCA, and ACA in Patient 2. Noninvasive angiography detected a left FPCA in both patients. While FPCA was clearly the mechanism of paradoxical infarction in Patient 2, it turned out to be an incidental finding in Patient 1 when evidence of a classic right PCA was uncovered from an old computed tomography scan image. Differences in anatomical details of the FPCA in each patient suggest that the 2 FPCAs are developmentally different. The FPCA of Patient 1 appeared to be an extension of the embryonic left posterior communicating artery (PcomA). Patient 2 had 2 PCAs on the left (PCA duplication), classic bilateral PCAs, and PcomAs, and absent left anterior choroidal artery (AchoA), suggesting developmental AchoA-to-FPCA transformation on the left. These 2 cases underscore the variable anatomy, clinical significance, and embryological origins of FPCA variants.",acetylsalicylic acid;warfarin;aged;anatomical variation;angiography;article;atrial fibrillation;Babinski reflex;brain blood flow;brain ischemia;case report;cerebral artery disease;computer assisted tomography;dementia;diffusion weighted imaging;echocardiography;electrocardiography;electroencephalography;female;fetal posterior cerebral artery;heart infarction;human;hyperlipidemia;hypertension;long term care;mitral valve replacement;nerve conduction disorder;neurologic examination;nuclear magnetic resonance imaging;posterior cerebral artery;posterior communicating artery;priority journal;somnolence;vertebral artery;very elderly,"Lambert, S. L.;Williams, F. J.;Oganisyan, Z. Z.;Branch, L. A.;Mader, E. C.",2016,,10.1177/2324709616665409,0,
3095,Memory complaints with and without memory impairment: the impact of leukoaraiosis on cognition,"White matter alterations, leukoaraiosis (LA) on structural MRI, are associated with cognitive deficits and increased risk of dementia. LA may also impact on subjective memory complaints in otherwise healthy older adults. Little is known about the interplay between LA memory complaints and cognition. We investigated cognitive phenotypes associated with LA in 42 non-demented older adults categorized as having subjective cognitive complaints with no objective cognitive impairment-the subjective cognitive impairment group (SCI; n = 12), amnesic mild cognitive impairment (aMCI; n = 20), or healthy controls (HC; n = 11). We measured LA severity on MRI with a 40-point visual rating scale. Controlling for age and Mini-Mental State Examination (MMSE) score, analyses revealed multiple between-group differences. Follow-up linear regression models investigating the underlying contributors to each clinic group's cognitive profile indicated that LA contributed to learning slope variance (after accounting for age and MMSE) but only for the SCI group. Although the SCI group showed a significantly steeper learning slope when compared to HC and aMCI, increasing LA severity negatively impacted this group's rate of learning. This, in conjunction with the significant contribution of age on SCI learning slope performance variance suggests that greater LA burden at a younger age may contribute to subtle changes in learning for individuals with subjective cognitive complaints.","Aged;Aged, 80 and over;Analysis of Variance;Cognition Disorders/diagnosis/*etiology;Female;Humans;Image Processing, Computer-Assisted;Leukoaraiosis/*complications/*psychology;Magnetic Resonance Imaging;Male;Memory Disorders/diagnosis/etiology/*psychology;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Pain Measurement;Predictive Value of Tests","Lamar, M.;Dannhauser, T. M.;Walker, Z.;Rodda, J. E.;Cutinha, D. J.;Shergill, S. S.",2011,Nov,10.1017/s1355617711001123,0,
3096,The impact of subcortical white matter disease on mood in euthymic older adults: a diffusion tensor imaging study,"OBJECTIVES: Clinical depression in the elderly is associated with cerebral small vessel disease. It is less certain whether the endorsement of depressive symptoms in the absence of clinical depression, relatively common in euthymic older adults, is also associated with white matter damage. The majority of studies exploring this issue have produced mixed results, perhaps due, in part, to differences in defining the threshold for depression, notating vascular risk factors, and/or the neuroimaging tools used to quantify white matter damage. We aimed to address these issues with non-demented euthymic older adults. DESIGN AND PARTICIPANTS: We performed diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) in a population based cohort of 79 individuals (mean age = 68 years). MEASUREMENTS: In addition to neuroimaging, the authors report assessments of overall cognition, executive functioning, and depression. RESULTS: Scores on the Geriatric Depression Scale 15-item (GDS-15) correlated with DTI measures of mean diffusivity (r [77] = 0.23, p = 0.039) and fractional anisotropy (r [77] = -0.22, p = 0.045) but only approached significance for T2-weighted MRI measures of white matter hyperintensities (WMH; r [77] = 0.21, p = 0.053). After adjusting for factors known to influence the development of WMH and depression, including age and vascular risks, DTI-derived indices of white matter integrity remained significantly associated with GDS-15 scores. Furthermore, only DTI-derived measures of white matter integrity contributed to the variance in GDS-15 scores in logistical regression modeling. CONCLUSIONS: These findings demonstrate an association between white matter damage and the endorsement of depressive symptoms in euthymic older adults and suggest that DTI may be more sensitive to this damage than T2-WMH in an aging cohort with multiple vascular risk factors.","Affect;Aged;Aged, 80 and over;Aging/pathology/psychology;Anisotropy;Brain/blood supply/ pathology/physiopathology;Cohort Studies;Depressive Disorder/ diagnosis/etiology/pathology;Diffusion Tensor Imaging;Executive Function;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Self-Assessment;Surveys and Questionnaires","Lamar, M.;Charlton, R. A.;Morris, R. G.;Markus, H. S.",2010,Jul,10.1097/JGP.0b013e3181cabad1,0,
3097,Prefrontal vulnerabilities and whole brain connectivity in aging and depression,"Studies exploring the underpinnings of age-related neurodegeneration suggest fronto-limbic alterations that are increasingly vulnerable in the presence of disease including late life depression. Less work has assessed the impact of this specific vulnerability on widespread brain circuitry. Seventy-nine older adults (healthy controls=45; late life depression=34) completed translational tasks shown in non-human primates to rely on fronto-limbic networks involving dorsolateral (Self-Ordered Pointing Task) or orbitofrontal (Object Alternation Task) cortices. A sub-sample of participants also completed diffusion tensor imaging for white matter tract quantification (uncinate and cingulum bundle; n=58) and whole brain tract-based spatial statistics (n=62). Despite task associations to specific white matter tracts across both groups, only healthy controls demonstrated significant correlations between widespread tract integrity and cognition. Thus, increasing Object Alternation Task errors were associated with decreasing fractional anisotropy in the uncinate in late life depression; however, only in healthy controls was the uncinate incorporated into a larger network of white matter vulnerability associating fractional anisotropy with Object Alternation Task errors using whole brain tract-based spatial statistics. It appears that the whole brain impact of specific fronto-limbic vulnerabilities in aging may be eclipsed in the presence of disease-specific neuropathology like that seen in late life depression. © 2013 Elsevier Ltd.",,"Lamar, M.;Charlton, R. A.;Ajilore, O.;Zhang, A.;Yang, S.;Barrick, T. R.;Rhodes, E.;Kumar, A.",2013,July,,0,
3098,The impact of region-specific leukoaraiosis on working memory deficits in dementia,"MRI leukoaraiosis (LA) is less likely to interfere with simple compared to more complex working memory (WM) skills. We hypothesize that LA within the left hemisphere negatively impacts higher-level WM processes in dementia. Participants with dementia (n=64; MMSE=22.0+/-3.4) performed a Backward Digit Task measuring simple storage/rehearsal (ANY-ORDER) and complex disengagement/temporal re-ordering (SERIAL-ORDER) recall. A visual rating scale categorized MRI-LA in five regions per hemisphere: frontal and parietal centrum semiovale, white matter around the frontal horns, body of the lateral ventricles and posterior horns. Amidst equivalent hemispheric LA scores [t(62)=-1.12, p>0.05], correlations revealed an association between left-sided LA and SERIAL-ORDER recall (r=-0.31, p=0.007) with LA around the posterior horn (rho=-0.30, p=0.008) and frontal centrum semiovale (rho=-0.29, p=0.01) showing the greatest association. Regression modeling confirmed the left posterior horn contribution to SERIAL-ORDER performance variance. Results suggest involvement of anterior (fronto-striatal) and more posterior (inferior parietal) white matter tracts in higher order WM deficits in dementia.","Aged;Aged, 80 and over;*Brain Mapping;Dementia/complications;Female;Humans;Leukoaraiosis/etiology/*pathology;Magnetic Resonance Imaging;Male;Memory Disorders/etiology/*pathology;Memory, Short-Term/*physiology;Neuropsychological Tests","Lamar, M.;Catani, M.;Price, C. C.;Heilman, K. M.;Libon, D. J.",2008,Aug,10.1016/j.neuropsychologia.2008.04.007,0,
3099,Imaging and neuropsychological correlates of white matter lesions in different subtypes of Mild Cognitive Impairment: A systematic review,"BACKGROUND: White matter lesions (WML) are prevalent in older adults. The association between WML and cognition in different subtypes of Mild Cognitive Impairment (MCI) is inconsistent in the literature. OBJECTVES: We aim to provide a systematic review on the impact of WML in different subtypes of MCI, and discuss the recent findings on white matter plasticity. METHODS: We reviewed peer-reviewed articles from January 2011 to August 2016 and identified 12 studies investigating the association between WML and subtypes of MCI with both neuroimaging and cognitive measures. RESULTS: Our review shows that 1) WM abnormality was identified between different subtypes of MCI and healthy controls on diffusion imaging; 2) neither visual ratings of WML nor its volumetry differentiate different subtypes of MCI or its prognosis to dementia; and 3) cognitive correlates of WML were evident in the Amnestic-type MCI in the domains of memory, language, psychomotor speed, attention and executive functions. CONCLUSION: Cognitive reserve and the plasticity of white matter may modulate the impact of WML on the manifestation of the neurodegenerative disease. Further research is needed to study the plasticity of white matter in the MCI population to evaluate its potential clinical application.",Mild Cognitive Impairment;White matter;cognition;cognitive reserve;neuroplasticity,"Lam, C. L. M.;Yiend, J.;Lee, T. M. C.",2017,,,0,
3100,Longitudinal white matter changes in frontotemporal dementia subtypes,"Frontotemporal dementia is a degenerative brain condition characterized by focal atrophy affecting the frontal and temporal lobes predominantly. Changes in white matter with disease progression and their relationship to grey matter atrophy remain unknown in FTD. This study aimed to establish longitudinal white matter changes and compare these changes to regional grey matter atrophy in the main FTD subtypes. Diffusion and T(1)-weighted images were collected from behavioral-variant FTD (bvFTD: 12), progressive non-fluent aphasia (PNFA: 10), semantic dementia (SD: 11), and 15 controls at baseline and 12 months apart. Changes in white matter integrity were established by fractional anisotropy, mean, axial and radial diffusivity measurements using tract-based spatial statistics. Patterns of cortical grey matter atrophy were measured using voxel-based morphometry. At baseline, bvFTD showed severe cross-sectional changes in orbitofrontal and anterior temporal tracts, which progressed to involve posterior temporal and occipital white matter over the 12-month. In PNFA, cross-sectional changes occurred bilaterally in frontotemporal white matter (left > right), with longitudinal changes more prominent on the right. Initial white matter changes in SD were circumscribed to the left temporal lobe, with longitudinal changes extending to bilateral frontotemporal tracts. In contrast, progression of grey matter change over time was less pronounced in all FTD subtypes. Mean diffusivity was most sensitive in detecting baseline changes while fractional anisotropy and radial diffusivity revealed greatest changes over time, possibly reflecting different underlying pathological processes with disease progression. Our results indicate that investigations of white matter changes reveal important differences across FTD syndromes with disease progression.","Aged;Anisotropy;Atrophy/etiology/pathology;Brain Mapping;Cross-Sectional Studies;Diffusion Tensor Imaging;Disease Progression;Female;Frontotemporal Dementia/classification/ complications;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/ diagnosis/ etiology;Longitudinal Studies;Male;Middle Aged;Neuropsychological Tests","Lam, B. Y.;Halliday, G. M.;Irish, M.;Hodges, J. R.;Piguet, O.",2014,Jul,,0,
3101,Lacunar infarctions due to cholesterol emboli,"Background and Purpose: Hypertension is commonly considered the major cause of lacunar infarctions. However, in some cases, it has been suggested that lacunes could be caused by cerebral emboli from cardiac or carotid sources. Cholesterol cerebral emboli have been rarely reported as a cause of lacunes. Case Description: We describe a 79-year-old patient with a progressive multi-infarct dementia who developed transient motor aphasia and paresis of the right arm. Computed tomography showed lacunar infarcts in the right caudate nucleus, left thalamus, and left putamen, as well as an old right frontal infarction. Neuropathological examination demonstrated no prominent vascular hyalinosis, but did show multiple cholesterol emboli occluding small arteries around lacunar infarcts and leptomeningeal arteries near cortical infarcts. The cholesterol material presumably originated in the extended atheromatous changes along the aortic arch. Conclusions: Our report confirms that lacunes can be caused by cholesterol emboli in some patients. Small cerebral emboli should not be overlooked as a cause of lacunes.",cholesterol;aged;article;brain infarction;case report;computer assisted tomography;embolism;female;histopathology;human;priority journal,"Laloux, P.;Brucher, J. M.",1991,,,0,
3102,Brain magnetic resonance imaging and neuropathology of cortical laminar necrosis,"Introduction. The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. Case report. A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral temporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Post-mortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. Conclusion. Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis. © 2007. Elsevier Masson SAS.",,"Laksiri, N.;Kaphan, E.;Pellissier, J. F.;Ali Chérif, A.",2007,March,,0,
3103,Preexisting cognitive impairment in intracerebral hemorrhage,"OBJECTIVES: Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. MATERIALS AND METHODS: We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of >/=3.44; an IQCODE >/=4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. RESULTS: Among the 89 participants, median age was 70 years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS>/=3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. CONCLUSIONS: In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH.",Aged;Cerebral Hemorrhage/ complications/diagnosis/epidemiology;Cognition Disorders/ complications/diagnosis/epidemiology;Female;Humans;Male;Middle Aged;activities of daily living;dementia;informant questionnaire on cognitive decline in the elderly;instrumental activities of daily living scale;intracerebral hemorrhage;prestroke cognitive impairment,"Laible, M.;Horstmann, S.;Mohlenbruch, M.;Schueler, S.;Rizos, T.;Veltkamp, R.",2017,Jun,,0,3104
3104,Preexisting cognitive impairment in intracerebral hemorrhage,"OBJECTIVES: Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. MATERIALS AND METHODS: We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of >/=3.44; an IQCODE >/=4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. RESULTS: Among the 89 participants, median age was 70 years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS>/=3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. CONCLUSIONS: In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH.",activities of daily living;dementia;informant questionnaire on cognitive decline in the elderly;instrumental activities of daily living scale;intracerebral hemorrhage;prestroke cognitive impairment,"Laible, M.;Horstmann, S.;Mohlenbruch, M.;Schueler, S.;Rizos, T.;Veltkamp, R.",2016,Aug 8,10.1111/ane.12646,0,
3105,Treatment With Prothrombin Complex Concentrate to Enable Emergency Lumbar Puncture in Patients Receiving Vitamin K Antagonists,"Study objective Lumbar punctures are frequently necessary in neurologic emergencies, but effective oral anticoagulation with vitamin K antagonists represents a contraindication. We report the effectiveness of prothrombin complex concentrates to reverse vitamin K antagonist to enable emergency lumbar punctures, as well as evaluate lumbar puncture– and prothrombin complex concentrates–related complications. Methods Consecutive patients treated with prothrombin complex concentrates between December 2004 and June 2014 to enable emergency lumbar puncture were included. International normalized ratio (INR) before and after prothrombin complex concentrates treatment and the time between start of reversal treatment and lumbar puncture were recorded. A target INR of less than or equal to 1.5 was defined as effective prothrombin complex concentrates treatment. Bleeding events, thromboembolic events, and allergic reactions after prothrombin complex concentrates treatment were identified and classified as “related,” “probably,” “possibly,” “unlikely related,” or “not related” to the lumbar puncture and prothrombin complex concentrates infusion. Results Thirty-seven patients were included (64.9% men; median age 76.0 years; interquartile range [IQR] 71.0 to 84.0 years). The intervention with prothrombin complex concentrates was effective in 33 of 37 patients (89.2%; 95% confidence interval [CI], 78.4% to 97.3%). The median INR was 2.2 (IQR 1.8 to 2.9; 95% CI, 1.9 to 2.5) before and 1.3 (IQR 1.2 to 1.4; 95% CI, 1.2 to 1.3) after prothrombin complex concentrates treatment. The median time between start of prothrombin complex concentrates treatment and lumbar puncture was 135 minutes (IQR 76 to 266 minutes; 95% CI, 84 to 198 minutes). One clinically irrelevant intracranial subdural hematoma “related” to the lumbar puncture developed. No allergic reaction was observed, but 2 of 37 patients (5.4%; 95% CI, 0% to 13.5%) experienced a thromboembolic event (1 ischemic stroke, classified “unlikely related,” and 1 myocardial infarction, “possibly related” to prothrombin complex concentrates treatment). Conclusion Reversing the effect of vitamin K antagonist with prothrombin complex concentrates to enable emergency lumbar puncture appears effective and safe, particularly in regard to bleeding events.",anticoagulant agent;antivitamin K;heparin;heparinoid;phenprocoumon;prothrombin complex;rivaroxaban;aged;allergic reaction;anticoagulant therapy;article;atrial fibrillation;brain disease;brain ischemia;brain lymphoma;cardiomyopathy;central nervous system infection;clinical article;computer assisted tomography;deep vein thrombosis;dementia;encephalitis;epileptic state;female;headache;heart infarction;human;international normalized ratio;intervertebral disk degeneration;lumbar puncture;lung embolism;male;mechanical heart valve;medical record review;meningitis;nuclear magnetic resonance imaging;osteochondrosis;outcome assessment;priority journal;subarachnoid hemorrhage;subdural hematoma,"Laible, M.;Beynon, C.;Sander, P.;Purrucker, J.;Müller, O. J.;Möhlenbruch, M.;Ringleb, P. A.;Rizos, T.",2016,,10.1016/j.annemergmed.2016.03.003,0,
3106,Schizophrenia in a patient with cerebral autosomally dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL disease),CADASIL is an autosomally dominantly inherited multi-infarct dementia caused by mutations in the Notch3 gene in chromosome 19. In this report we present the first patient in the world literature with CADASIL and schizophrenia and discuss the co-occurrence of these conditions in the light of the literature.,Notch receptor;adult;artery disease;article;autosomal dominant disorder;brain cortex;brain infarction;case report;chromosome 19;comorbidity;dementia;female;gene mutation;human;leukoencephalopathy;medical literature;nuclear magnetic resonance imaging;nucleotide sequence;psychologic test;schizophrenia,"Lagas, P. A.;Juvonen, V.",2001,,,0,
3107,Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease,"This study compared 32 patients with ischemic vascular dementia (IVD) to 32 patients with probable Alzheimer's disease (AD) on select language and verbal memory tests. The IVD and AD patients were individually matched on the basis of age, dementia severity, years of education, and gender. The IVD patients had poorer verbal fluency, but better free recall, fewer recal intrusions, and better recognition memory than the AD patients. Relationships between the neuropsychological measures and radiological indexes of cortical and subcortical pathology were also examined. Number of infarcts, white-matter lucency, and ventricular enlargement correlated with some of the neuropsychological measures; cortical atrophy correlated with most of the measures. The findings suggest that neuropsychological deficits in IVD may be related to dysfunction of frontal-subcortical circuits, although an associated degenerative cortical process may also be involved.","Aged;Alzheimer Disease/*psychology;Brain Ischemia/pathology/psychology;Cerebral Ventricles/pathology;Dementia, Multi-Infarct/pathology/psychology;Dementia, Vascular/pathology/*psychology;Female;Humans;Magnetic Resonance Imaging;Male;Memory/*physiology;Mental Recall/physiology;Neuropsychological Tests;Verbal Behavior/*physiology","Lafosse, J. M.;Reed, B. R.;Mungas, D.;Sterling, S. B.;Wahbeh, H.;Jagust, W. J.",1997,Oct,,0,
3108,Neurocognitive deficits and diffusion MR imaging abnormalities in a case of adult-onset autosomal dominant leukodystrophy,"Autosomal dominant adult-onset leukodystrophy (ADLD) is a progressive hereditary disease caused by duplication of Lamin B1 on chromosome 5q23.2. It is characterized by autonomic dysregulation, pyramidal signs, and cerebellar dysfunction. Since the first description in 1984, no authors have reported on its neurocognitive sequelae or attempted to quantify the severity of white matter changes. Herein we report a case of ADLD presenting with progressive cognitive changes leading to dementia and its associated white matter damage using diffusion MR imaging. © Versita Sp. z o.o.",,"Laforce Jr, R.;Roy, M.;Descoteaux, M.;Berthelot, C.;Bouchard, J. P.",2013,December,,0,
3109,A clinical approach to vascular (multiinfarct) dementia,"71 patients with an ischaemic stroke were investigated clinically, by psychological tests (WAIS) and Computertomography. On the basis of the investigation the patients were separated into two groups. 40 patients showed early dementia; 31 were without mental impairment. The frequency of strokes, the history of neurological symptoms and the neurological symptoms at admission were distributed evenly. The dominant hemisphere was significantly more often diseased in the demented group; bilateral signs were also significantly more often seen in the demented group. From the investigated risk factors (Hypertension, Cardiac disease, Diabetes, Viscosity, Fibrinogen). Only hypertension was significantly more often present in demented than non demented patients. The CT confirmed the clinical findings, especially the importance of the bilateral distribution of infarcts as well as a higher distribution of infarction in the thalamus in the demented patient group.","Brain Ischemia/complications;Dementia/*diagnosis/epidemiology;Dominance, Cerebral;Humans;Hypertension/complications;Risk;Thalamus/blood supply;Tomography, X-Ray Computed;Wechsler Scales","Ladurner, G.;Lliff, L. D.;Sager, W. D.;Lechner, H.",1982,,,0,
3110,[Relation between multiple infarcts and vascular (multi-infarct) dementia] Die Beziehung zwischen multiplen infarkten und vaskularer (Multiinfarkt-) Demenz,"77 patients with multiple infarcts in computerized tomography have been investigated. In 10 patients no definitive stroke could be found in the history, 2 had TIAs only. In 20 cases a PRIND and in 45 a completed stroke could be observed. More than one stroke was only present in 28 patients. In 68 of the patients without remarkable aphasia or decreased level of consciousness the psychiatric findings showed 37 patients with and 31 without a dementia. The CT findings showed in the patients with dementia significantly more often infarcts in the dominant hemisphere, whereas atrophy was found in a similar distribution in both groups.","Adult;Aged;Atrophy;Brain/pathology;Cerebral Infarction/ diagnosis;Dementia/ diagnosis;Diagnosis, Differential;Dominance, Cerebral;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Ladurner, G.;Jeindl, E.;Schneider, G.",1983,Mar,,0,
3111,[Relation between multiple infarcts and vascular (multi-infarct) dementia],"77 patients with multiple infarcts in computerized tomography have been investigated. In 10 patients no definitive stroke could be found in the history, 2 had TIAs only. In 20 cases a PRIND and in 45 a completed stroke could be observed. More than one stroke was only present in 28 patients. In 68 of the patients without remarkable aphasia or decreased level of consciousness the psychiatric findings showed 37 patients with and 31 without a dementia. The CT findings showed in the patients with dementia significantly more often infarcts in the dominant hemisphere, whereas atrophy was found in a similar distribution in both groups.","Adult;Aged;Atrophy;Brain/pathology;Cerebral Infarction/*diagnosis;Dementia/*diagnosis;Diagnosis, Differential;Dominance, Cerebral;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Ladurner, G.;Jeindl, E.;Schneider, G.",1983,Mar,10.1055/s-2007-1002221,0,
3112,Clinical factors associated with dementia in ischaemic stroke,"71 patients with an ischaemic stroke were studied. The patients were separated into two groups on the basis of the results of clinical investigation, computed tomography and psychological testing (WAIS). 40 patients showed an early dementia and 31 were without mental impairment. The mean age was 57 years in the demented group and 54 years in the non-demented group. The mean duration of the history of cerebrovascular disease was also not statistically different in both groups. The frequency of strokes was identical since 50% of the patients in both groups had more than one stroke. The history of neurological symptoms together with the neurological deficits seen on admission were distributed evenly. The dominant hemisphere was more often diseased in the demented group. Bilateral symptoms were also more common in the demented stroke patients. The WAIS showed a similar IQ in both groups but the deterioration index was significantly altered in the demented group. Hypertension was the only risk factor which differed between both groups. Cardiac disease, diabetes, viscosity and fibrinogen did not differ in both groups. The CT showed more normal scans in the non-demented group, the distribution of atrophy on its own and infarction in the left or right hemisphere were both inconclusive, whilst patients with bilateral infarcts were more common in the dementia group. Also, generalised atrophy in combination with an infarct was found more often in the demented patients.","Brain Ischemia/diagnosis/*psychology;Cerebrovascular Disorders/diagnosis/*psychology;Dementia/diagnosis/*psychology;Female;Humans;Male;Middle Aged;Psychological Tests;Tomography, X-Ray Computed","Ladurner, G.;Iliff, L. D.;Lechner, H.",1982,Feb,,0,
3113,"The Disconnection Hypothesis in Alzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging","According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.",,"Lacalle-Aurioles, M.;Navas-Sanchez, F. J.;Aleman-Gomez, Y.;Olazaran, J.;Guzman-De-Villoria, J. A.;Cruz-Orduna, I.;Mateos-Perez, J. M.;Desco, M.",2016,Feb 5,10.3233/jad-150288,0,
3114,Is the cerebellum the optimal reference region for intensity normalization of perfusion MR studies in early Alzheimer's disease?,"The cerebellum is the region most commonly used as a reference when normalizing the intensity of perfusion images acquired using magnetic resonance imaging (MRI) in Alzheimer's disease (AD) studies. In addition, the cerebellum provides unbiased estimations with nuclear medicine techniques. However, no reports confirm the cerebellum as an optimal reference region in MRI studies or evaluate the consequences of using different normalization regions. In this study, we address the effect of using the cerebellum, whole-brain white matter, and whole-brain cortical gray matter in the normalization of cerebral blood flow (CBF) parametric maps by comparing patients with stable mild cognitive impairment (MCI), patients with AD and healthy controls. According to our results, normalization by whole-brain cortical gray matter enables more sensitive detection of perfusion abnormalities in AD patients and reveals a larger number of affected regions than data normalized by the cerebellum or whole-brain white matter. Therefore, the cerebellum is not the most valid reference region in MRI studies for early stages of AD. After normalization by whole-brain cortical gray matter, we found a significant decrease in CBF in both parietal lobes and an increase in CBF in the right medial temporal lobe. We found no differences in perfusion between patients with stable MCI and healthy controls either before or after normalization.",Aged;Alzheimer Disease/ pathology;Brain/ pathology;Cerebellum/ pathology;Cerebrum/blood supply;Female;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment;Reference Values;Regional Blood Flow,"Lacalle-Aurioles, M.;Aleman-Gomez, Y.;Guzman-De-Villoria, J. A.;Cruz-Orduna, I.;Olazaran, J.;Mateos-Perez, J. M.;Martino, M. E.;Desco, M.",2013,,10.1371/journal.pone.0081548,0,
3115,Dural arteriovenous fistulas presenting with reversible dementia are associated with a specific venous drainage,BACKGROUND AND PURPOSE: Venous drainage of dural arteriovenous fistula (DAVF) with dementia has never been reported. The aim of this study was to discover if specific vascular conditions exist to develop dementia in patients with DAVF. METHODS: Venous drainage in patients embolized in our centre between 1996 and 2012 for a DAVF with dementia were qualitatively analyzed and compared with a control group without dementia. RESULTS: Eight patients with dementia and 45 control patients were included. The prevalence of dementia was 4%. Diffuse hemispheric white matter lesions on magnetic resonance imaging (MRI) were consistently associated with dementia. Cognitive symptoms dramatically improved after embolization. The consistent angiographic feature in patients with dementia was drainage of the DAVF into both the straight sinus and the superior sagittal sinuses. Only two patients in the control group had similar abnormalities. CONCLUSIONS: The association of a reflux from the fistula into the straight sinus and the superior sagittal sinuses is a necessary condition to develop such a reversible dementia in DAVF. Venous hypertension in the territory of transparenchymal veins may explain this reversal phenomenon. A rapidly progressive dementia with diffuse white matter lesions on MRI should evoke this diagnosis to the physician.,"Adolescent;Adult;Aged;Aged, 80 and over;Central Nervous System Vascular Malformations/ complications/ therapy;Dementia/ complications;Drainage/ methods;Female;Humans;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Retrospective Studies;Young Adult","Labeyrie, M. A.;Lenck, S.;Saint-Maurice, J. P.;Bresson, D.;Houdart, E.",2014,Mar,10.1111/ene.12300,0,
3116,Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging,"The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.","Adult;Aged;Alzheimer Disease/ pathology;Atrophy/pathology;Brain Mapping;Cerebral Cortex/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, Emission-Computed","Labbe, C.;Froment, J. C.;Kennedy, A.;Ashburner, J.;Cinotti, L.",1996,Fall,,0,
3117,MRI pattern approach of adult-onset inherited leukoencephalopathies,"White matter hyperintensities are frequently encountered in clinical practice. In adulthood, white matter hyperintensities are generally related to acquired disorders, such as vascular, inflammatory, or demyelinating diseases. Symmetrical and confluent white matter abnormalities on the first available MRI suggest a genetic disorder. In this article, we provide keys to recognize and classify the adult-onset forms of inherited leukoencephalopathies and to identify their causes by targeting specific biochemical or molecular biomarkers.",adult onset inherited leukoencephalopathy;article;autosomal dominant inheritance;CADASIL;clinical practice;gene mutation;genetic disorder;human;intracranial aneurysm;leukoencephalopathy;microangiopathy;migraine with aura;mood disorder;neuroimaging;nuclear magnetic resonance imaging;priority journal;recessive inheritance;retina hemorrhage;vascular disease;white matter,"Labauge, P.;Carra-Dalliere, C.;De Champfleur, N. M.;Ayrignac, X.;Boespflug-Tanguy, O.",2014,,,0,
3118,MR T2 relaxometry in Alzheimer's disease and age-associated memory impairment,"A prolonged MR T2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T2 relaxometry in diagnosing early AD. T2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T2 in the right hippocampal head (104 +/- 11 ms) and tail (98 +/- 10 ms) than age-matched controls (95 +/- 5 and 92 +/- 9 ms, respectively). This prolongation was not related to age. In the AD group, the T2 of the left hippocampal head also correlated with the clinical severity. The T2 of the amygdala did not differ across the groups. Increased T2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T2 comparable with those of age-matched controls. Despite the prolongation of T2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T2 relaxometry is not a reliable method for diagnosing early AD.",Adult;Age Distribution;Aged;Alzheimer Disease/*pathology/*physiopathology;Female;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/*physiopathology;Middle Aged,"Laakso, M. P.;Partanen, K.;Soininen, H.;Lehtovirta, M.;Hallikainen, M.;Hanninen, T.;Helkala, E. L.;Vainio, P.;Riekkinen, P. J., Sr.",1996,Jul-Aug,,0,
3119,Brain N-acetyl-L-aspartic acid in Alzheimer's disease: a proton magnetic resonance spectroscopy study,"This study was performed in order to measure changes in brain N-acetyl-L-aspartic acid (NAA) in post-mortem brain tissue in Alzheimer's disease (AD) in comparison to normal control subjects using the technique of magnetic resonance spectroscopy. Brain tissue was obtained at autopsy and frozen until use, from seven patients diagnosed according to current research criteria for AD and 7 control subjects. Detailed clinical evaluations were available for all the dementia cases. Representative brain samples were obtained from three neocortical regions and a limbic region (parahippocampal gyrus) in white and grey matter. NAA was quantified on perchloric acid extracts using proton nuclear magnetic resonance (NMR) spectroscopy. Regional NAA did not vary significantly with age. In AD, reductions were present in the grey matter of the neocortex but not in the white matter. Within the parahippocampal gyrus there were reductions in both tissue types; only cortical levels correlated with clinical scales of dementia severity. A pattern of increasing correlation was observed between dementia severity as measured by the mini mental state examination during life and NAA levels from brain areas of increasing pathological predilection in AD. These post-mortem studies show reductions in brain NAA in AD which correlate with dementia severity during life and which support the use of future in vivo NAA spectroscopic images in the evaluation of AD patients.","Aged;Aged, 80 and over;Alzheimer Disease/ enzymology/pathology;Aspartic Acid/ analogs & derivatives/metabolism;Cerebral Cortex/ enzymology/pathology;Female;Hippocampus/ enzymology/pathology;Humans;Magnetic Resonance Spectroscopy;Male;Middle Aged","Kwo-On-Yuen, P. F.;Newmark, R. D.;Budinger, T. F.;Kaye, J. A.;Ball, M. J.;Jagust, W. J.",1994,Dec 26,,0,
3120,Significant association of metabolic syndrome with silent brain infarction in elderly people,"A silent brain infarction (SBI) can predict clinical overt stroke or dementia. Studies focusing on the elderly population, where SBI is most common, are sparse. We examined the associations between SBI and metabolic syndrome (MetS) in healthy elderly individuals. Neurologically healthy subjects (1,254 persons, 723 males) aged > or =65 years who underwent brain MRI were evaluated. MetS was diagnosed following the AHA/NHLBI-2005 criteria. We examined associations between full syndrome (at least three of the five conditions) as well as its components and SBI while controlling for possible confounders. One hundred and ninety-seven subjects (15.7%) were found to have one or more SBIs on MRI. Age (1-year difference) was found to be significantly related to SBI prevalence (OR 1.09; 95% CI 1.05-1.12). MetS was significantly associated with SBI (OR 1.68; 95% CI 1.15-2.44). The component model of MetS showed a strong significance between elevated blood pressure (OR 1.89; 95% CI 1.23-2.91) and SBI. Subjects exhibiting more components of MetS showed more prevalent SBI and multiple SBIs. MetS was found to be significantly associated with SBI in neurologically healthy elderly people. The positive trend between the number of MetS components and SBI could be used as a diagnostic tool to predict and prevent future stroke.","Age Factors;Age of Onset;Aged;Aged, 80 and over;Brain Infarction/*complications/diagnosis;Female;*Geriatric Assessment;Humans;Magnetic Resonance Imaging/methods;Male;Metabolic Syndrome X/*complications;Risk Factors;Severity of Illness Index","Kwon, H. M.;Kim, B. J.;Park, J. H.;Ryu, W. S.;Kim, C. K.;Lee, S. H.;Ko, S. B.;Nam, H.;Lee, S. H.;Lee, Y. S.;Yoon, B. W.",2009,Nov,10.1007/s00415-009-5201-8,0,
3121,Metabolic syndrome as an independent risk factor of silent brain infarction in healthy people,"BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is associated with an increased risk of the subsequent development of cardiovascular disease or stroke. Moreover, a silent brain infarction (SBI) can predict clinical overt stroke or dementia. We examined the associations between SBI and MetS in apparently healthy individuals. METHODS: We evaluated 1588 neurologically healthy subjects (927 males and 661 females) who underwent brain MRI at Seoul National University Hospital Healthcare System Gangnam Center. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III. We examined associations between full syndrome (> or =3 of the 5 conditions) as well as its components and SBI by controlling possible confounders. RESULTS: Eighty-eight (5.5%) were found to have > or =1 SBI on MRI. Age was found to be significantly related to SBI prevalence (odds ratio [OR], 1.06; 95% CI, 1.04 to 1.09). A history of coronary artery disease was associated with an elevated odds ratio of SBI (OR, 2.83; 95% CI, 1.38 to 5.82), and MetS was significantly associated with SBI (OR, 2.18; 95% CI, 1.38 to 3.44). The components model of MetS showed a strong significance between an elevated blood pressure (OR, 3.75; 95% CI, 2.05 to 6.85) and an impaired fasting glucose (OR, 1.74; 95% CI, 1.08 to 2.80) and the risk of SBI. CONCLUSIONS: MetS was found to be significantly associated with SBI. This finding has clinical utility in terms of identifying healthy people at increased risk of developing SBI.","Adult;Age Factors;Aged;Aged, 80 and over;Brain/pathology;Brain Infarction/*pathology;C-Reactive Protein/biosynthesis;Cardiovascular Diseases/pathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Metabolic Syndrome X/*pathology;Middle Aged;Odds Ratio;Risk;Risk Factors;Stroke/diagnosis;Vascular Diseases/pathology","Kwon, H. M.;Kim, B. J.;Lee, S. H.;Choi, S. H.;Oh, B. H.;Yoon, B. W.",2006,Feb,10.1161/01.str.0000199081.17935.81,0,
3122,Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function,"Background: The mechanism of dementia in subcortical cerebral infarction is incompletely understood. Objective: To determine how cognitive function is related to cortical metabolism in patients with subcortical infarction and a continuum of cognitive impairment. Methods: We used positron emission tomography (PET) and the glucose metabolic tracer fludeoxyglucose F 18 to study 8 patients with subcortical stroke and normal cognitive function (S- CN), 5 patients with subcortical stroke and cognitive impairment (S-CI) who did not have dementia, 8 patients with subcortical stroke and dementia (S- D), and 11 controls with no cognitive impairment or stroke. A subset of patients had absolute regional cerebral metabolic rate of glucose (CMRglc) determined, while in all subjects regional tracer uptake normalized to whole brain tracer uptake was calculated. PET data were analyzed by constructing volumes of interest using coregistered magnetic resonance imaging data and correcting the PET data for atrophy. Results: Global CMRglc was significantly lower in the patients with S-D than in the control and S-CN groups, with S- CI rates intermediate to those of the S-D and S-CN groups. Absolute regional CMRs of glucose were similar in the S-D and S-CI groups and in the control and S-CN groups. The regional pattern, however, showed lower right frontal regional CMRglc ratios in all stroke groups compared with the controls. There were modest correlations between performance on the Mini-Mental State Examination and whole brain CMRglc when all 4 groups were included. Conclusions: These results demonstrate that subcortical infarction produces global cerebral hypometabolism, which is related to the clinical status of the patients. In addition, specific frontal lobe hypometabolism also appears to be a feature of subcortical infarction. Taken together, both global and regional effects on cortical function mediate the production of clinical symptoms in patients with subcortical strokes.",,"Kwan, L. T.;Reed, B. R.;Ebcrling, J. L.;Schliff, N.;Tanabc, J.;Norman, D.;Vcincr, M. W.;Jagust, W. J.",1999,July,,0,
3123,Non-obese fatty liver disease is associated with lacunar infarct,"BACKGROUND/AIMS: Lacunar infarct, a small subcortical ischaemic lesion, is a known risk factor for future cognitive impairment, dementia and stroke. We evaluated the relationship between fatty liver disease (FLD) and lacunar infarct in a healthy general population. METHODS: Subjects who underwent brain magnetic resonance imaging (MRI) and abdominal ultrasonography (US) during health check-ups from 2007 to 2009 were included. FLD was diagnosed by US. Subjects with a history of cerebrovascular disease, radiological findings consistent with cerebrovascular stenosis or cerebral small vessel disease were excluded. RESULTS: Of the 1277 subjects, 54 (4.2%) exhibited lacunar infarct, and 514 (40.3%) had FLD. Subjects with lacunar infarct had a higher prevalence of FLD (59.3% vs 39.4%, P = .004). There was significant interaction between obesity (BMI < 25 kg/m(2) vs >/= 25 kg/m(2) ) and FLD for lacunar infarct (P for interaction = .024). Subgroup analysis revealed that non-obese FLD was more common in the subjects with lacunar infarct than those without (51.7% vs 23.5%, P = .001). However, there was no significant difference in the obese FLD prevalence between these 2 groups. In multivariate models adjusted by age, sex, smoking, alcohol, hypertension and diabetes, FLD was significantly associated with lacunar infarct (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.08-3.58; P = .027). Non-obese FLD was associated with lacunar infarct (OR 3.58; 95% CI 1.63-7.89; P = .002); however, this association remained insignificant in obese FLD. Instead, ageing and hypertension were independent risk factors for lacunar infarct in the obese population. CONCLUSIONS: FLD is significantly associated with lacunar infarct, independent of traditional risk factors. This association was prominent in the non-obese population.",atherosclerosis;cerebral infarct;hepatic steatosis;lacunar infarct,"Kwak, M. S.;Kim, K. W.;Seo, H.;Chung, G. E.;Yim, J. Y.;Kim, D.",2017,Dec 8,,0,
3124,Brain white matter structure and information processing speed in healthy older age,"Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (gspeed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the gspeed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and gspeed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.",aged;aging;alcohol consumption;article;diffusion tensor imaging;diffusion weighted imaging;disease association;female;follow up;fractional anisotropy;human;image analysis;information processing;information processing speed;intelligence;longitudinal study;major clinical study;male;medical history;mental deterioration;Mini Mental State Examination;neurologic examination;priority journal;response time;Wechsler adult intelligence scale;white matter,"Kuznetsova, K. A.;Maniega, S. M.;Ritchie, S. J.;Cox, S. R.;Storkey, A. J.;Starr, J. M.;Wardlaw, J. M.;Deary, I. J.;Bastin, M. E.",2016,,,0,
3125,Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: A possible manifestation of immune reconstitution inflammatory syndrome,"Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome. © 2013 Japanese Society of Neuropathology.",amphotericin B;methylprednisolone;prednisolone;aged;article;astrocyte;autopsy;brain cortex;brain cortex lesion;case report;cause of death;cell proliferation;cerebrospinal fluid;consciousness disorder;cryptococcal meningitis;Cryptococcus neoformans;degenerative disease;drowsiness;drug dose reduction;human;human tissue;immune reconstitution inflammatory syndrome;Japanese (people);lymphadenopathy;lymphocyte count;lymphocytic infiltration;male;neuroimaging;nuclear magnetic resonance imaging;priority journal;respiratory failure;skin biopsy;skin disease;sweet disease;white matter lesion,"Kuwahara, H.;Tsuchiya, K.;Kobayashi, Z.;Inaba, A.;Akiyama, H.;Mizusawa, H.",2014,,,0,
3126,Cerebral blood flow and vascular response to hypercapnia in hypertensive patients with leukoaraiosis,"Both arteriosclerosis and leukoaraiosis have a close relationship with hypertension, but the relationship between cerebral hemodynamics and leukoaraiosis in hypertensive patients has not been fully examined. To clarify this issue, we measured the regional cerebral blood flow (rCBF) and cerebrovascular response to hypercapnia in hypertensive patients with various degrees of leukoaraiosis. The subjects consisted of 7 normotensive normal controls and 17 hypertensive patients. The hypertensive patients were divided into three groups according to the severity of white matter lesions (leukoaraiosis) on MRI and the presence of dementia, namely, (1) negative or mild leukoaraiosis without dementia, (2) moderate to severe leukoaraiosis without dementia and (3) severe leukoaraiosis with dementia. Both the rCBF and the cerebrovascular response to hypercapnia were measured by the O-15 H2O bolus-injection method and positron emission tomography. The rCBF in hypertensive patients without dementia did not decrease when compared with the normotensive controls, but the rCBF in hypertensive patients with dementia markedly decreased in the cerebral cortices and white matter. On the other hand, the cerebrovascular response to hypercapnia declined with the severity of leukoaraiosis, and it decreased most severely in patients with severe leukoaraiosis and dementia. Our results indicate that the reduction in the cerebral hemodynamic reserve capacity has a close relationship with the severity of leukoaraiosis in hypertensive patients, although the rCBF is maintained in hypertensive patients without dementia, and suggest that arteriosclerotic change reduces cerebrovascular CO2 response and causes a leukoaraiosis in hypertensive patients.",adult;aged;article;brain blood flow;cardiovascular autoregulation;clinical article;controlled study;female;human;hypercapnia;hypertension;leukoaraiosis;male;nuclear magnetic resonance imaging;positron emission tomography;priority journal,"Kuwabara, Y.;Ichiya, Y.;Sasaki, M.;Yoshida, T.;Fukumura, T.;Masuda, K.;Ibayashi, S.;Fujishima, M.",1996,,,0,
3127,Comparison of I-123 IMP and Tc-99m HMPAO SPECT studies with PET in dementia,"We compared I-123 IMP and 99m-Tc HMPAO SPECT studies with 0-15 H2O and F-18 FDG PET studies, and evaluated the clinical significance of SPECT studies in dementia. Seventeen patients including 9 patients with Alzheimer's disease, 3 patients with Pick's disease and 5 patients with multi-infarct dementia were studied. IMP and HMPAO SPECT studies could not detect mildly affected areas when compared with FDG PET. However, they revealed decreased perfusion in the bilateral parietal regions in Alzheimer's disease and in the bilateral frontal regions in Pick's disease, while MRI and/or CT showed mild to moderate cerebral atrophy. IMP and HMPAO SPECT studies can be easily performed in clinical practice, and these findings were useful in the differential diagnosis of dementia. Our preliminary results suggested that SPECT studies with I-123 IMP and Tc-99m HMPAO, despite their limitations, are useful in the differential diagnosis of dementia.","Aged;Alzheimer Disease/radionuclide imaging;*Amphetamines;Dementia/*radionuclide imaging;Dementia, Multi-Infarct/radionuclide imaging;Female;Humans;Iodine Radioisotopes;Iofetamine;Male;Middle Aged;*Organotechnetium Compounds;*Oximes;Technetium Tc 99m Exametazime;*Tomography, Emission-Computed;*Tomography, Emission-Computed, Single-Photon","Kuwabara, Y.;Ichiya, Y.;Otsuka, M.;Tahara, T.;Fukumura, T.;Gunasekera, R.;Ichimiya, A.;Masuda, K.",1990,Nov,,0,
3128,Binswanger's type encephalopathy without alopecia and lumbago in young hypotensive patients,"Binswanger's type encephalopathy is characterized by progressive dementia and diffuse subcortical ischemic lesions associated with arteriosclerosis. Hypertension is believed to be a major pathogenic factor in causing this encephalopathy but there are some cases of the encephalopathy not suffering from hypertension. In 1985, Yamamura et al. and Fukutake et al. reported familial cases of normotensive juvenile Binswanger's type encephalopathy with alopecia and lumbago, and considered it to be possibly a new clinical syndrome. We reported three cases of relatively young-onset (under the age of 40) Binswanger's type encephalopathy with persistent hypotension. All three patients suffered from neither alopecia nor lumbago. Patient (male aged 40) had repeated episodes of ischemic stroke and had progressive dementia. Patients 2 (male aged 41) and 3 (male aged 34) were not in a state of dementia, but had a history of transient ischemic attacks, and at present are completely symptom-free. Though there were no risk factors for cerebrovascular disease in these cases, the repeated episodes of ischemic stroke and the existence of small multiple lacunes in the basal ganglia on CT and MRI suggest that the white matter damage was principally due to a vascular disorder. In these cases, persistent hypotension was characteristic and might be a factor for the induction and exacerbation of this encephalopathy. These three cases are different from the classic form of Binswanger's type encephalopathy based on hypertension. Normotensive cases have been described before, but our cases do not seem to fall into this category because the blood pressure constantly remained hypotensive. Moreover because of the absence of both alopecia and lumbago, they were clearly different from the cases reported by Yamamura and Fukutake. Thus, the present cases might be a new version of Binswanger's type encephalopathy not recognized before.",adult;article;brain disease;case report;computer assisted tomography;dementia;human;hypotension;male;nuclear magnetic resonance;spondylosis,"Kusuhara, T.;Hino, H.;Ayabe, M.;Shoji, H.;Iijima, H.",1994,,,0,
3129,Renal involvement in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary systemic arteriopathy presenting with migraines, mood disorders, focal neurologic deficits, recurrent ischemic attacks and dementia in young adults. The genesis of this disease relates to missense mutation of the Notch3 gene. We report here a newly identified CADASIL patient and discuss unique vascular lesions observed in the kidney. A 64-year-old female was admitted to our hospital for the investigation of proteinuria, hematuria and progressive neurological abnormalities. Her mother and brother died of cerebral infarction at a relatively young age despite a lack of apparent risk factors for arteriosclerosis. Over the past 4 months before admission, she had suffered from frequent transient ischemic attacks despite appropriate antiplatelet therapy. Blood examination revealed mild renal insufficiency and urinalysis revealed moderate protein excretion and dysmorphic hematuria. Magnetic resonance imaging of the brain revealed multiple infarcts and leukoencephalopathy. Histopathological analysis of the kidney revealed focal segmental mesangial proliferation, the loss and degeneration of arterial medial smooth muscle cells and arterial intimal thickening. Immunofluorescence analysis of glomeruli revealed IgA deposition in the mesangial area. Electron microscope analysis revealed electron-dense deposition also in the mesangial area. In addition, granular osmophilic material (GOM) was observed in the extra-glomerular mesangial area and around the vascular smooth muscle cells. Genetic analysis of Notch3 revealed an R141C missense mutation and she was diagnosed with CADASIL complicated with IgA nephropathy. In immunohistological analysis, Notch3 stains were positive in vascular smooth muscle cells of the interlobular arteries and both afferent and efferent arterioles, and weak in the glomerular mesangial area. Antihypertensive treatment using angiotensin II receptor blocker and a low protein diet were initiated, and her urinary protein excretion decreased to 0.2 g/day. However, due to the progression of her neurological abnormalities, she became socially withdrawn. In CADASIL, GOM, abnormal accumulation of Notch3 ectodomain, is thought to induce the degeneration and loss ofvascular smooth muscle cells and subsequent intinial thickening. Analysis of our cases provided that these morphological abnormalities were also observed in the CADASIL patient kidney. © 2007 Dustri-Verlag Dr. K. Feistle.",,"Kusaba, T.;Hatta, T.;Kimura, T.;Sonomura, K.;Tanda, S.;Kishimoto, N.;Kameyama, H.;Okigaki, M.;Mori, Y.;Ishigami, N.;Mizuno, T.;Nakagawa, M.;Matsubara, H.",2007,March,,0,
3130,Neurological disorders with demyelinating brain white matter lesions in a patient with rheumatoid arthritis treated with etanercept,"We present the case of a 37-year-old woman with severe, drug-resistant rheumatoid arthritis. The patient has been previously treated with several disease-modifying anti-rheumatic drugs as well as infliximab alone and in combination therapy. Despite the treatment, a high disease activity persisted. For this reason, the patient was qualified to etanercept therapy. During the therapy, a gradual joint condition improvement was demonstrated, including arthritis remission. From the fourth month of etanercept administration, neurological disorders such as sight and speech disorders, amentia and muscle weakening were reported. The symptoms aggrevated with therapy continuation. The patient reported her complaints to her leading rheumatologist after 8 months of their duration. Optic fundus and visual area examination, as well as in the neurological examination no significant abnormalities were found. Magnetic resonance imaging of the head demonstrated single, small hyperintensive lesions in the T2w images located in the white matter of the frontal and parietal lobes of the left cerebral hemisphere, which could be identical with demyelization. Based on the clinical and laboratory findings, drug-induced neurological disorders associated with etanercept administration were suspected. After discontinuation of etanercept therapy, the complaints gradually subsided. The amentia episodes, concentration disorders and speech disorders were less frequent. There was no relapse of muscle weakening. Within 6 months of the drug discontinuation, neurological symptoms resolved completely. Copyright by Medycyna Praktyczna, 2008.",,"Kur-Zalewska, J.;Swarowska-Knap, J.;Tłustochowicz, W.",2008,2008,,0,
3131,Potential biological markers for cerebrovascular disease,"Cerebrovascular diseases can causes cognitive impairment and dementia by loss of neurons and synaptic connections, destruction of axons, and demyelinization. Biological markers including genetic tests, brain imaging techniques, and biochemical assays in the CSF are valuable for the identification and quantification of cerebrovascular diseases. Genetic tests may be used to detect mutations that cause hereditary cerebral amyloid angiopathies or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Structural CT and MR imaging is routinely used to visualize and quantify infarcts and white-matter changes. Functional SPET and PET imaging can demonstrate focal and remote effects of vascular lesions on cerebral blood flow and metabolism. Biochemical imaging using proton MRS is a nonspecific marker for neuronal and axonal damage. Among biochemical markers in the CSF, tau protein, phospho-tau, and beta amyloid protein are helpful to differentiate vascular dementia from Alzheimer's disease.","Aged;Biomarkers;Blood-Brain Barrier/physiology;Brain/pathology/radiography/radionuclide imaging;CADASIL/complications/diagnosis;Cerebral Amyloid Angiopathy/complications/diagnosis/genetics;Cerebrovascular Disorders/ complications/diagnosis/physiopathology;Dementia, Vascular/ complications;Humans;Magnetic Resonance Imaging;Myelin Sheath/pathology;Nerve Degeneration/pathology;Positron-Emission Tomography;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Kurz, A.;Riemenschneider, M.;Wallin, A.",2003,,10.1017/s1041610203009025,0,
3132,Occurrence of paroxysmal synchronous EEG discharges in subcortical arteriosclerotic encephalopathy (Binswanger's disease),"A 72-year-old patient with von Recklinghausen's disease showed akinetic mutism within 6 months of the onset of dementia. The findings of diffuse cerebral atrophy on CT and periodic synchronous discharges (PSDs) in EEG suggested Creutzfeldt-Jakob disease. However, autopsy findings of diffuse softening of the subcortical white matter and marked arteriosclerotic changes of the subcortical arterioles with sparing of the cortex in the cerebrum confirmed a diagnosis of Binswanger's disease. Binswanger's disease should be included in the differential diagnosis of dementia showing PSDs in EEG.",aged;article;autopsy;case report;Creutzfeldt Jakob disease;differential diagnosis;electroencephalography;human;male;multiinfarct dementia;neurofibromatosis;pathology;pathophysiology,"Kuroda, Y.;Ikeda, A.;Kurohara, K.;Kakigi, R.;Ryuh, S.;Kouda, H.;Misago, N.;Sugihara, H.",1993,,,0,
3133,Association between alpha-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI,"BACKGROUND: The anti-aging protein, alpha-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of alpha-Klotho in the brain has not been sufficiently investigated. OBJECTIVE: Here, we investigated the association between alpha-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). METHODS: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood alpha-Klotho level were retrospectively investigated. RESULTS: The alpha-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the alpha-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low alpha-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. CONCLUSION: A reduced blood alpha-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The alpha-Klotho level may serve as a useful clinical index of vascular cognitive impairment.",deep white matter lesion;dementia;magnetic resonance imaging;alpha-Klotho,"Kuriyama, N.;Ozaki, E.;Mizuno, T.;Ihara, M.;Mizuno, S.;Koyama, T.;Matsui, D.;Watanabe, I.;Akazawa, K.;Takeda, K.;Takada, A.;Inaba, M.;Yamada, S.;Motoyama, K.;Takeshita, W.;Iwai, K.;Hashiguchi, K.;Kobayashi, D.;Kondo, M.;Tamura, A.;Yamada, K.;Nakagawa, M.;Watanabe, Y.",2018,,,0,
3134,CD62-mediated activation of platelets in cerebral white matter lesions in patients with cognitive decline,"BACKGROUND: Vascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. METHODS: A total of 143 individuals (70.4 +/- 6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. RESULTS: Significant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean+2SD of the Grade 0 group, and the odds ratio of the Grade 2+3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. CONCLUSION: Elevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline.","Aged;Blood Platelets/ pathology;Cognition;Cognition Disorders/ pathology;Dementia, Vascular;Female;Humans;Hypertension/ pathology;Intracranial Arteriosclerosis;Magnetic Resonance Imaging;Male;Middle Aged;P-Selectin/ metabolism;Platelet Activation/ physiology;Risk Factors;White Matter/ pathology","Kuriyama, N.;Mizuno, T.;Yasuike, H.;Matsuno, H.;Kawashita, E.;Tamura, A.;Ozaki, E.;Matsui, D.;Watanabe, I.;Koyama, T.;Miyatani, F.;Kondo, M.;Tokuda, T.;Ohshima, Y.;Muranishi, M.;Akazawa, K.;Takada, A.;Takeda, K.;Matsumoto, S.;Mizuno, S.;Yamada, K.;Nakagawa, M.;Watanabe, Y.",2016,Jan-Feb,10.1016/j.archger.2015.09.001,0,
3135,Association between Mid-Regional Proadrenomedullin Levels and Progression of Deep White Matter Lesions in the Brain Accompanying Cognitive Decline,"BACKGROUND: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain. OBJECTIVE: To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. METHODS: The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels. RESULTS: MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008. CONCLUSION: MR-proADM levels were significantly different between the DWML groups and inversely correlated with cognitive function test scores, suggesting that high MR-proADM levels and DWMLs are associated with cognitive decline. Therefore, the MR-proADM level may be an effective candidate as a potential diagnostic surrogate marker of cognitive decline.",Deep white matter lesion;dementia;magnetic resonance imaging;mid-regional proadrenomedullin,"Kuriyama, N.;Ihara, M.;Mizuno, T.;Ozaki, E.;Matsui, D.;Watanabe, I.;Koyama, T.;Kondo, M.;Tokuda, T.;Tamura, A.;Yamada, K.;Akazawa, K.;Takeda, K.;Takada, A.;Mizuno, S.;Nakagawa, M.;Watanabe, Y.",2017,,,0,
3136,Failure of CT scan to detect ischemic lesions in patients with dementia,"Although clinical series have described relatively high accuracy in the ability of computed tomographic (CT) scan to detect significant cerebrovascular damage in patients with dementia, a recent neuropathologically controlled study failed to document that relationship. We now present clinical, neuroradiologic (CT), and neuropathologic information on four patients in whom CT scans did not contribute to the diagnosis of multi-infarct dementia or mixed dementia, despite clinical and neuropathologic evidence of infarcts. In one patient, the failure of CT scan to detect ischemic lesions may be attributable to less sensitive neuroradiologic criteria in use at the time of the examination. In the other three, even neuroradiologic review after the pathology was known failed to reveal the infarcts. These observations suggest the advisability of caution in using CT scan as a criterion for the presence or absence of cerebrovascular damage in patients with dementia.",aged;article;brain ischemia;brain tomography;case report;computer assisted tomography;dementia;diagnostic accuracy;diagnostic value;female;human;male;multiinfarct dementia;neuropathology;neuroradiology;priority journal,"Kurita, A.;Black, R. S.;Blass, J. P.;Deck, D. F.;Nolan, K. A.",1993,,,0,
3137,MRI evaluation of AIDS-related encephalopathy: toxoplasmosis vs. lymphoma,"The spectrum of cranial MRI findings was evaluated in 113 patients with the acquired immunodeficiency syndrome, assessing lesion number, size, location, and configuration in association with the autopsy and/or biopsy results. Correlation of cranial MRI and CT was performed in 32 patients. MRI was shown to be superior in sensitivity of lesion detection demonstrating more lesions than CT in 14 studies (44%) and equivalent information in 18 studies (56%). In no case did CT demonstrate lesions not detected on MRI. We conclude that MRI should be the study of choice in evaluating AIDS-related encephalopathy. Multiple lesions that involve both deep gray matter and white matter suggest the possibility of CNS lymphoma. The ""target"" appearance on MRI is not helpful in distinguishing toxoplasmosis from lymphoma.","AIDS Dementia Complex/*diagnosis/pathology;Adult;Brain/*pathology;Brain Diseases/*diagnosis;Brain Neoplasms/*diagnosis/pathology;Diagnosis, Differential;Female;Humans;Lymphoma/*diagnosis/pathology;*Magnetic Resonance Imaging;Male;Middle Aged;Opportunistic Infections/*diagnosis/pathology;Toxoplasmosis/*diagnosis/pathology","Kupfer, M. C.;Zee, C. S.;Colletti, P. M.;Boswell, W. D.;Rhodes, R.",1990,,,0,
3138,Structural gray and white matter changes in patients with HIV,"In this cross-sectional study we used magnetic resonance imaging (MRI)-based voxel based morphometry (VBM) in a sample of HIV positive patients to detect structural gray and white matter changes. Forty-eight HIV positive subjects with (n = 28) or without (n = 20) cognitive deficits (mean age 48.5 +/- 9.6 years) and 48 age- and sex-matched HIV negative controls underwent MRI for VBM analyses. Clinical testing in HIV patients included the HIV dementia scale (HDS), Unified Parkinson's Disease Rating Scale (UPDRS) and the grooved pegboard test. Comparing controls with HIV positive patients with cognitive dysfunction (n = 28) VBM showed gray matter decrease in the anterior cingulate and temporal cortices along with white matter reduction in the midbrain region. These changes were more prominent with increasing cognitive decline, when assigning HIV patients to three cognitive groups (not impaired, mildly impaired, overtly impaired) based on performance in the HIV dementia scale. Regression analysis including all HIV positive patients with available data revealed that prefrontal gray matter atrophy in HIV was associated with longer disease duration (n = 48), while motor dysfunction (n = 48) was associated with basal ganglia gray matter atrophy. Lower CD4 cell count (n = 47) correlated with decrease of occipital gray matter. Our results provide evidence for atrophy of nigro-striatal and fronto-striatal circuits in HIV. This pattern of atrophy is consistent with motor dysfunction and dysexecutive syndrome found in HIV patients with HIV-associated neurocognitive disorder.","Adult;Aged;Analysis of Variance;Anti-Retroviral Agents/therapeutic use;Antigens, CD4/metabolism;Brain/ pathology/virology;Brain Mapping;Case-Control Studies;Cognition Disorders/etiology;Female;HIV Infections/complications/drug therapy/immunology/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Movement Disorders/etiology;Neuropsychological Tests;Regression Analysis","Kuper, M.;Rabe, K.;Esser, S.;Gizewski, E. R.;Husstedt, I. W.;Maschke, M.;Obermann, M.",2011,Jun,10.1007/s00415-010-5883-y,0,
3139,"Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1","OBJECTIVES: To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients. MATERIALS AND METHODS: Seventeen patients with classic DM1 were administered intelligence and neuropsychological tests and brain MRI focusing on a semi-quantitative rating scale of subcortical white matter lesions (WMLs). Statistical analysis was measured to evaluate the correlation among clinical manifestations, intelligence, brain MRI abnormalities, and CTG repeat expansion. RESULTS: There were statistically significant correlations between intelligence test and insular WMLs for all DM1 patients and between intelligence quotient and temporal WMLs for those patients with less than 400 of the CTG repeat size. We also documented that temporal WMLs were related to the disease course, and frontal WMLs were correlated with aging in all DM1 patients. However, a poor correlation was found among CTG repeat size and clinical pictures, neuropsychological impairments, and brain MRI abnormalities in all DM1 patients. CONCLUSION: These results suggest that subcortical WMLs are correlated with focal dementia in classic DM1 patients. Temporal and insular WMLs may be responsible for the global intellectual dysfunction of adult DM1 patients.","Adolescent;Adult;Brain/ pathology;Female;Humans;Intelligence/ physiology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Myotonic Dystrophy/genetics/pathology/physiopathology;Myotonin-Protein Kinase;Neuroglia/ pathology;Neuropsychological Tests/statistics & numerical data;Protein-Serine-Threonine Kinases/ genetics;Statistics, Nonparametric;Trinucleotide Repeat Expansion/ genetics","Kuo, H. C.;Hsieh, Y. C.;Wang, H. M.;Chuang, W. L.;Huang, C. C.",2008,Feb,10.1111/j.1600-0404.2007.00911.x,0,
3140,Detection of amyloid plaques by radioligands for Abeta40 and Abeta42: potential imaging agents in Alzheimer's patients,"Alzheimer s disease (AD) is linked to increased brain deposition of amyloid-beta (Abeta) peptides in senile plaques (SPs), and recent therapeutic efforts have focused on inhibiting the production or enhancing the clearance of Abeta in brain. However, it has not been possible to measure the burden of SPs or assess the effect of potential therapies on brain Abeta levels in patients. Toward that end, we have developed a novel radioligand, [(125)I]TZDM, which binds Abeta fibrils with high affinity, crosses the blood-brain barrier (BBB), and labels amyloid plaques in vivo. Compared to a styrylbenzene probe, [(125)I]IMSB, [(125)I]TZDM showed a 10-fold greater brain penetration and labeled plaques with higher sensitivity for in vivo imaging. However, this ligand also labels white matter, which contributes to undesirable high background regions of the brain. Interestingly, parallel to their differential binding characteristics onto fibrils composed of 40 (Abeta40)- or 42 (Abeta42)-amino-acid-long forms of Abeta peptides, these radioligands displayed differential labeling of SPs in AD brain sections under our experimental conditions. It was observed that [(125)I]IMSB labeled SPs containing Abeta40, amyloid angiopathy (AA), and neurofibrillary tangles, whereas [(125)I]TZDM detected only SPs and Abeta42-positive AA. Since increased production and deposition of Abeta42 relative to Abeta40 may be crucial for the generation of SPs, [(125)I]TZDM and related derivatives may be more attractive probes for in vivo plaque labeling. Further structural modifications of TZDM to lower the background labeling will be needed to optimize the plaque-labeling property.","Alzheimer Disease/metabolism/pathology/ radionuclide imaging;Amyloid beta-Peptides/ metabolism;Animals;Artifacts;Binding, Competitive/drug effects;Blood-Brain Barrier/drug effects/physiology;Brain/metabolism/pathology/ radionuclide imaging;Humans;Immunohistochemistry;Iodine Radioisotopes;Mice;Mice, Transgenic;Nerve Fibers, Myelinated/metabolism;Peptide Fragments/ metabolism;Plaque, Amyloid/metabolism/pathology/ radionuclide imaging;Radionuclide Imaging/instrumentation/methods;Reproducibility of Results;Styrenes/pharmacokinetics;Thiazoles/pharmacokinetics","Kung, M. P.;Skovronsky, D. M.;Hou, C.;Zhuang, Z. P.;Gur, T. L.;Zhang, B.;Trojanowski, J. Q.;Lee, V. M.;Kung, H. F.",2003,Feb,10.1385/jmn:20:1:15,0,
3141,Binding of two potential imaging agents targeting amyloid plaques in postmortem brain tissues of patients with Alzheimer's disease,"In vivo imaging of amyloid plaques may be useful for evaluation and diagnosis of Alzheimer's disease (AD) patients. Towards that end, we have developed 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2]pyridine (IMPY), and 4-N-methylamino-4'-hydroxystilbene (SB-13) as ligands for specifically targeting amyloid plaques. These ligands can be readily radiolabeled with I-123 or C-11, for in vivo imaging using single photon emission computerized tomography (SPECT) or positron emission tomography (PET), respectively. However, in order to be useful in vivo, probes must show selective high affinity binding to a sufficiently abundant binding site on amyloid plaques. Therefore, as a prelude to in vivo imaging studies, we evaluated the binding properties of these two potential imaging agents to amyloid plaques present in human brain tissues. In vitro binding studies were carried out with [(125)I]IMPY and [(3)H]SB-13 in homogenates prepared from postmortem samples of affected cortex and cerebellum of pathologically confirmed AD patients and age-matched controls. Binding parameters such as K(d) and B(max) were estimated. Competition study was designed to evaluate the amyloid plaque binding specificity using human brain tissues. Plaque binding was confirmed by thioflavin-S staining. Specific [(125)I]IMPY or [(3)H]SB-13 binding can be clearly measured in the cortical gray matter, but not in the white matter of AD cases. There was a very low specific binding in cortical tissue homogenates of control brains. Cerebellar homogenates prepared from either AD or control brains did not show any specific [(125)I]IMPY or [(3)H]SB-13 binding. The K(d) values of AD cortical homogenates were 5.3+/-1.0 and 2.4+/-0.2 nM for [(125)I]IMPY and [(3)H]SB-13, respectively. High binding capacity and comparable values were observed for both ligands (14-45 pmol/mg protein). The location and density of specific signal detected by [(125)I]IMPY or [(3)H]SB-13 correlated with the distribution of amyloid plaques in these brain specimens, as confirmed by thioflavin-S staining. Competition profiles of known ligands suggest that the binding is highly selective and comparable to that reported by using preformed Abeta peptide aggregates. [(125)I]IMPY and [(3)H]SB-13 show an abundant binding capacity with high binding affinities for amyloid plaques in affected cortical regions of AD brains. These properties suggest that when labeled with I-123 or C-11, these two ligands may be useful to quantitate amyloid plaque burdens in the living AD patients.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/pathology;Brain/ metabolism/ pathology;Dose-Response Relationship, Drug;Drug Delivery Systems/methods;Humans;Plaque, Amyloid/ metabolism/pathology;Positron-Emission Tomography/methods;Protein Binding/physiology;Pyridines/metabolism;Radioisotopes/ metabolism;Tomography, Emission-Computed, Single-Photon/methods","Kung, M. P.;Hou, C.;Zhuang, Z. P.;Skovronsky, D.;Kung, H. F.",2004,Oct 29,10.1016/j.brainres.2004.08.004,0,
3142,Associations between brain imaging characteristics and cognition in post-stroke patients,"Background: Cerebrovascular disease is the main risk factor for dementia. Post-stroke dementia is a major cause of disability in adults and seniors. Ischemic lesions in certain areas of the brain can lead to cognitive and neuropsychiatric symptom change. Objective: To investigate association among brain imaging characteristics, vascular risk factors, and cognitive function in post stroke patients; to examine for risk factors of post-stroke dementia; and to evaluate interrater agreement between CT and MRI, with specific regard to white matter lesions. Material and Method: This observational study in 100 stroke patients aged more than 15 years was conducted at Siriraj Hospital in Bangkok, Thailand. Brain imaging (CT or MRI) was performed in all patients. Cognitive and neuropsychiatric status was evaluated at 2-4 weeks after discharge and at the 6-12 month follow-up visit. Dementia was defined according to DSM IV criteria. Risk factors for and odd ratios of post-stroke dementia were analyzed. Results: Dementia was diagnosed in 15 of 85 patients (17.6%). Vascular dementia was the most commonly observed type of dementia. Anterior circulation stroke (p = 0.033, OR: 4.5), lacunar infarction (p = 0.022, OR: 5.46), severe central atrophy (p = 0.042,OR: 14.67), and anterior white matter lucencies (p = 0.028, OR: 4.27) were all significantly different between the dementia and non-dementia groups. Risk factors associated with post-stroke dementia were educational level less than 6 years (p = 0.012, OR: 15.2), history of previous stroke (p = 0.048, OR: 3.88), and diabetes mellitus (p = 0.049, OR: 6.9). Interrater agreement for white matter lesion visual rating between CT and MRI brain was 0.637. No significant association between neuropsychiatric symptoms and brain lesion was found. Conclusion: Prevalence of post-stroke dementia in this study was 17.6%. Combination of multiple clinical risk factors (DM, history of previous stroke, and low educational level) and brain lesion (anterior circulation, central atrophy, and anterior WML) can contribute to development of post-stroke dementia. Among brain imaging findings, severe central atrophy had the strongest association with dementia (OR: 14.7). Among evaluated risk factors, educational level less than 6 years was the strongest predictor of post-stroke dementia (OR: 15.2). CT scan of the brain was reliable, compared to MRI, for detecting white matter lesion (kappa level = 0.637, 75.5% agreement).",adult;aged;Alzheimer disease;anterior circulation stroke;article;brain disease;cardiovascular risk;cerebrovascular accident;cognition;cognitive defect;computer assisted tomography;controlled study;cross-sectional study;dementia assessment;diabetes mellitus;DSM-IV;education;experimental cognitive test;female;functional neuroimaging;human;lacunar stroke;major clinical study;male;mental disease;multiinfarct dementia;neuropsychiatric inventory;nuclear magnetic resonance imaging;observational study;stroke patient;thai mental state examination;verbal fluency test;white matter lesion;white matter lucency,"Kumutpongpanich, T.;Senanarong, V.",2017,,,0,
3143,Major neurocognitive disorder following isolated hippocampal ischemic lesions,"BACKGROUND AND PURPOSE: Major cognitive disorder (MND) following vascular events is known as second causes of dementia after Alzheimer's disease (AD). Acute onset MND due to isolated hippocampal infarction has not been recognized as a specific subtype of vascular dementia, and there is no validated criteria for the identification of such cases, either clinically or radiologically. RESULTS: Among 7200 patients with first-ever ischemic stroke, 22 patients (0.3%) showed acute isolated ischemic lesions in the hippocampus. Four of them presented acute MND characterized by confusion at the beginning of stroke and thereafter they developed typical clinical characteristics of MND. These cases allowed us to delineate a specific type of dementia characterized by confusion at stroke onset, dull and aimless appearance, verbal and visual immediate or delayed memory deficits, dysexecutive syndrome. Major cognitive disorder was developed due to anterior involvement of the hippocampus with little interindividual variation. Stroke mechanism was artery-to-artery embolism or cardioembolism which can explain isolated infarcts of the hippocampus. CONCLUSIONS: Hippocampal MND generally occurred in acute bilateral isolated hippocampal infarcts. The clinical characteristic of MND may be secondary to lesions of the body of the hippocampus and interruption of the hippocampo-temporal pathways and cortical projections.","Aged;Brain Ischemia/ complications/diagnostic imaging/ pathology;Cognition Disorders/diagnostic imaging/ etiology;Female;Hippocampus/diagnostic imaging/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies;Dementia;Hippocampus;Ischemic stroke;Memory;Vascular major neurocognitive disorder","Kumral, E.;Zirek, O.",2017,Jan 15,,0,
3144,Isolated hippocampal infarcts: Vascular and neuropsychological findings,"BACKGROUND AND PURPOSE: The hippocampus plays a role in the verbal and spatial memory processing, learning, and emotions. The purpose of this study was to determine clinical, etiological, and radiological features of isolated hippocampal infarcts. METHODS: We reviewed, 6800 patients with first-ever ischaemic stroke included in our Stroke Registry between 2004 and 2014. Among them we studied 19 patients with an acute isolated hippocampal infarct confirmed by MRI. RESULTS: Among 6800 patients, 19 patients (0.03%) showed ischaemic lesions in the hippocampal artery territory, allowing us to delineate 5 variant distributions; (1) anterior hippocampal infarcts (4 patients [21%]) were present with altered consciousness, transient visual vivid hallucinations, and transient global amnesia with episodic and verbal memory deficits. (2) Posterior hippocampal infarcts (3 patients [16%]) developed dizziness and dullness at stroke onset, confusion, episodic and procedural memory deficit and verbal learning deficit. (3) Unilateral complete hippocampal infarcts were present (4 patients [21%]) with confusion, object specific hallucinations, intense mood states changes as well as impulsivity or depressive behaviour. Memory dysfunctions were found in all patients. (4) Bilateral hippocampal infarcts (3 patients [16%]) had cognitive deficits and memory deficits in all patients. All patients had difficulties retrieving specific autobiographical events and retrieving recent memory, and disturbances of learning in verbal and visual task. Hippocampal dementia was observed in 2 patients with severe immediate, delayed verbal and visual memory deficits, dysexecutive syndrome, deficits in responding to feedback and error correction with dull and aimless appearance lasting several months. (5) Small circumscribed (punctiform) hippocampal infarcts (5 patients [26%]) showed dizziness or dullness sensation and difficulties finding words or objects that they use everyday. Cardioembolism (10; 53%) and large-artery disease of the vertebrobasilar system (6; 32%) were the main stroke mechanisms. CONCLUSIONS: We described topographic patterns of hippocampal infarction with distinct manifestations and etiologies. We thought that different patterns of hippocampal infarcts are the result of variation in hippocampal arterial supply or reflect a source of embolism.",Cardioembolism;Hippocampal infarct;Large-artery disease;Mri;Memory deficits,"Kumral, E.;Deveci, E. E.;Erdogan, C.;Enustun, C.",2015,Sep 15,10.1016/j.jns.2015.06.011,0,
3145,Toxins in brain! magnetic resonance (Mr) imaging of toxic leukoencephalopathy – a pictorial essay,"Toxic leukoencephalopathy results from damage to the white matter caused by various toxins. It manifests itself as white matter signal abnormalities with or without the presence of restricted diffusion. These changes are often reversible if the insulting agent is removed early, with the exception of posthypoxic leukoencephalopathy that can manifest itself 1–2 weeks after the initial insult. However, many other potential causes of white matter signal abnormalities can mimic the changes of toxic leukoencephalopathy. Thus, familiarity with the causes, clinical presentation and particularly imaging findings of toxic leukoencephalopathy is critical for early treatment and improved prognosis. The purpose of this pictorial essay is to familiarize the reader with the various causes of toxic leukoencephalopathy along with its differential diagnoses and mimics.",neurotoxin;article;brain toxicity;brain tumor;carbon monoxide intoxication;delayed posthypoxic leukoencephalopathy;demyelinating disease;drug abuse;genetic disorder;gliomatosis cerebri;HIV associated dementia;human;leukodystrophy;metabolic disorder;nuclear magnetic resonance imaging;posterior reversible encephalopathy syndrome;progressive multifocal leukoencephalopathy;radiation injury;subacute sclerosing panencephalitis;vascular disease;white matter injury,"Kumar, Y.;Drumsta, D.;Mangla, M.;Gupta, N.;Hooda, K.;Almast, J.;Mangla, R.",2017,,10.12659/pjr.901791,0,
3146,Incidental brain MRI abnormalities in 60- to 64-year-old community-dwelling individuals: data from the Personality and Total Health Through Life study,"OBJECTIVE: There have been limited data available on the prevalence of structural brain abnormalities in asymptomatic individuals and a growing interest in the various ethical issues related to reporting of such findings. This study evaluated the prevalence of incidental abnormalities on brain magnetic resonance imaging (MRI) in a random sample of 60- to 64-year-old community-dwelling individuals as well as successfully followed a referral pathway taking into account of the various ethical issues related to the referral process. The Personality and Total Health (PATH) Project was designed to study the risk and protection factors of normal ageing, dementia and other neuropsychiatric disorders. METHOD: MRI scans were performed in randomly selected 478 healthy, community-dwelling 60- to 64-year-old individuals. All scans were reported for abnormalities by a radiologist. RESULTS: Abnormalities were detected in 22 (4.8%) subjects, comprising 10 tumours (pituitary adenoma 4, meningioma 3, suprasellar tumour 1, cavernous haemangioma 1, subarachnoid lipoma 1), 6 infarct-like lesions, 2 arachnoid cysts, 1 possible normal pressure hydrocephalus, and 1 each of unconfirmed aneurysm and mesial temporal sclerosis. Further evaluation led to novel intervention in one case of pituitary adenoma, and adjustment of drug treatment to modify risk factors in two cases with subclinical infarction. CONCLUSION: While no case required immediate referral or urgent surgical intervention, the change in the outcome of treatment of some cases suggests that appropriate referral process should be in place when researchers study large number of subjects in the community using MRI of the brain.",,"Kumar, R.;Sachdev, P. S.;Price, J. L.;Rosenman, S.;Christensen, H.",2008,Apr,10.1111/j.1601-5215.2008.00273.x,0,
3147,Clinical and neuroimaging correlates of mild cognitive impairment in a middle-aged community sample: The personality and total health through life 60+ study,"This cross-sectional study aimed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60+ project. 2,551 community-dwelling individuals in the age range of 60-64 years were recruited randomly through the electoral roll. They were screened using Mini-Mental State Examination and a short cognitive battery. Those who screened positive underwent detailed medical and neuropsychological assessments. Of the 224 subjects who screened positive, 117 underwent a detailed assessment. Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI. Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls. Subjects were clinically evaluated for depressive symptoms and major and minor depression syndromes. Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios, cortical atrophy measures, hippocampal volumes, volumes of amygdala and white matter hyperintensities after adjusting for age, gender, years of education, depression and physical disability. None of the neuroanatomical substrates appeared as predictors of MCI. The only predictors were higher depression scores and fewer years of education. Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects. It may be that this age group is too young for such brain changes to be identified. Copyright © 2006 S. Karger AG.",,"Kumar, R.;Parslow, R. A.;Jorm, A. F.;Rosenman, S. J.;Maller, J.;Meslin, C.;Anstey, K. J.;Christensen, H.;Sachdev, P. S.",2006,December,,0,
3148,MR findings in adult-onset adrenoleukodystrophy,"PURPOSE: To describe the MR findings of brain and spinal cord in adult-onset adrenoleukodystrophy. METHODS: One hundred sixty-four adult patients ranging from 19 to 74 years of age (119 men and 45 women) with clinically and biochemically proved adrenoleukodystrophy underwent MR of the brain. In 30 patients the spinal cord also was evaluated with MR. RESULTS: The brain MR findings were abnormal in 54 of 119 males and in 9 of 45 female heterozygotes and consisted of varying degrees of demyelination of the cerebral white matter in 40 patients, corpus callosum in 25 patients, corticospinal tracts in 46 patients, visual tracts in 31 patients, and auditory tracts in 18 patients. The thoracic spinal cord showed diffuse atrophy in 18 of 20 men and in 8 of 10 women. CONCLUSION: It is important to recognize the MR findings of adult-onset adrenoleukodystrophy, because not uncommonly the clinical and MR findings of adrenoleukodystrophy are misdiagnosed as multiple sclerosis, olivopontocerebellar or spinocerebellar atrophy, amyotrophic lateral sclerosis, or dementia. Analysis of the MR findings and correlation of the clinical findings has permitted a tentative subdivision of adult-onset adrenoleukodystrophy population into four subtypes that appear to differ in respect to prognosis and possibly pathogenesis. MR evaluation of the brain in adrenoleukodystrophy also is helpful in patient selection for experimental therapy, which is most effective if offered in the early stage of the disease.",Adrenoleukodystrophy/*diagnosis/genetics;Adult;Aged;Atrophy;Brain/*pathology;Female;Heterozygote Detection;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/pathology;Neural Pathways/pathology;Neurologic Examination;Spinal Cord/*pathology,"Kumar, A. J.;Kohler, W.;Kruse, B.;Naidu, S.;Bergin, A.;Edwin, D.;Moser, H. W.",1995,Jun-Jul,,0,
3149,"Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study","BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.",African Continental Ancestry Group/genetics;Aged;Apolipoproteins E/blood/*genetics;Brain/*anatomy & histology/pathology;Cardiovascular Diseases/*epidemiology;Cerebral Infarction/epidemiology;*Cognition;Cognition Disorders/*epidemiology;European Continental Ancestry Group;Female;Genotype;Health Status;Humans;*Magnetic Resonance Imaging;Male;Mental Status Schedule;Polymerase Chain Reaction;Risk Factors;Sex Factors;United States,"Kuller, L. H.;Shemanski, L.;Manolio, T.;Haan, M.;Fried, L.;Bryan, N.;Burke, G. L.;Tracy, R.;Bhadelia, R.",1998,Feb,,0,
3150,"Relationship of hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women's Health Initiative Memory Study (WHIMS)-MRI trial","This paper evaluates the relationship of blood pressure (BP) levels at Women's Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study-Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP > or = 140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP > or = 140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia.","Age Factors;Aged;Antihypertensive Agents/ therapeutic use;Blood Pressure/ drug effects;Brain/pathology;Drug Therapy, Combination;Estrogen Replacement Therapy;Estrogens, Conjugated (USP)/therapeutic use;Female;Follow-Up Studies;Humans;Hypertension/ diagnosis/ drug therapy;Hypertensive Encephalopathy/ diagnosis;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Medroxyprogesterone Acetate/therapeutic use;Memory/ drug effects;Mental Status Schedule;Multicenter Studies as Topic;Randomized Controlled Trials as Topic;United States","Kuller, L. H.;Margolis, K. L.;Gaussoin, S. A.;Bryan, N. R.;Kerwin, D.;Limacher, M.;Wassertheil-Smoller, S.;Williamson, J.;Robinson, J. G.",2010,Mar,10.1111/j.1751-7176.2009.00234.x,0,
3151,Risk factors for dementia in the cardiovascular health cognition study,"BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.","Aged;Aged, 80 and over;Apolipoproteins E/genetics;Cardiovascular Diseases/ complications/genetics/pathology;Cognition Disorders/ etiology/genetics/pathology;Dementia/ etiology/genetics/pathology;Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Odds Ratio;Predictive Value of Tests;Proportional Hazards Models;Risk Factors","Kuller, L. H.;Lopez, O. L.;Newman, A.;Beauchamp, N. J.;Burke, G.;Dulberg, C.;Fitzpatrick, A.;Fried, L.;Haan, M. N.",2003,Jan-Feb,67109,0,
3152,Determinants of vascular dementia in the Cardiovascular Health Cognition Study,"OBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia. METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. RESULTS: Approximately 44% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke. CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/pathology/physiopathology;Atrophy/etiology/pathology/physiopathology;Brain/blood supply/*pathology;Cardiovascular Diseases/epidemiology/pathology/physiopathology;Cerebral Arteries/*pathology/physiopathology;Cerebral Infarction/epidemiology/pathology/physiopathology;Cohort Studies;Comorbidity/trends;Continental Population Groups;Dementia, Vascular/*epidemiology/*pathology/physiopathology;Female;Humans;Lateral Ventricles/pathology/physiopathology;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Risk Factors;Sex Factors","Kuller, L. H.;Lopez, O. L.;Jagust, W. J.;Becker, J. T.;DeKosky, S. T.;Lyketsos, C.;Kawas, C.;Breitner, J. C.;Fitzpatrick, A.;Dulberg, C.",2005,May 10,10.1212/01.wnl.0000160115.55756.de,0,
3153,Risk of dementia and death in the long-term follow-up of the Pittsburgh Cardiovascular Health Study-Cognition Study,"INTRODUCTION: Increasing life expectancy has resulted in a larger population of older individuals at risk of dementia. METHODS: The Cardiovascular Health Study-Cognition Study followed 532 participants from 1998-99 (mean age 79) to 2013 (mean age 93) for death and dementia. RESULTS: Risk of death was determined by extent of coronary artery calcium, high-sensitivity cardiac troponin, brain natriuretic peptide, and white matter grade. Significant predictors of dementia were age, apolipoprotein-E4, vocabulary raw score, hippocampal volume, ventricular size, cognitive performance, and number of blocks walked. By 2013, 160 of 532 were alive, including 19 cognitively normal. Those with normal cognition had higher grade education, better cognition test scores, greater hippocampal volume, faster gait speed, and number of blocks walked as compared with survivors who were demented. DISCUSSION: Few survived free of dementia and disability. Prevention and delay of cognitive decline for this older population is an imperative.",Aging;Cognition;Dementia;Epidemiology;Mri,"Kuller, L. H.;Lopez, O. L.;Becker, J. T.;Chang, Y.;Newman, A. B.",2016,Feb,10.1016/j.jalz.2015.08.165,0,
3154,White matter grade and ventricular volume on brain MRI as markers of longevity in the cardiovascular health study,"High white matter grade (WMG) on magnetic resonance imaging (MRI) is a risk factor for dementia, stroke and disability. Higher ventricular size is a marker of brain ""atrophy."" In the Cardiovascular Health Study (CHS) (n = 3245) mean age 75 years, 50% black and 40% men, we evaluated WM and ventricular grade (VG), total, cardiovascular and noncardiovascular mortality and longevity before and after adjusting for numerous determinants of longevity over an approximate 10-12 years of follow-up. A low WMG and VG was a marker for low total, cardiovascular and noncardiovascular mortality and for increased longevity over 10+ years of follow-up. We estimated that a 75-year-old with WMG below median would have about a 5-6 years greater longevity and for VG about 3 years, than above the median even after adjustment for numerous risk factors. Low WMG and VG on MRI is a powerful determinant of long-term survival among older individuals. © 2006 Elsevier Inc. All rights reserved.",,"Kuller, L. H.;Arnold, A. M.;Longstreth Jr, W. T.;Manolio, T. A.;O'Leary, D. H.;Burke, G. L.;Fried, L. P.;Newman, A. B.",2007,September,,0,
3155,Risk factors for dementia in the Cardiovascular Health Study cognition study] Factores de riesgo de la demencia en el Cardiovascular Health Study Cognition Study,"Several predispocitional and genetic factors are thought to be involved in the etiology of Alzheimer s disease (AD). Except for age, there is no consensus among researchers about the factors that can best predict AD. Some studies have found that, older women, cerebrovascular risk factors (hypertension, ischemic heart disease, diabetes mellitus), and the presence of the apolipoprotein E (APOE) 4 allele to be associated with the development of dementia and AD. However, there are a few large scale studies that have entered magnetic resonance imaging (MRI) findings in the analysis of risk factors for AD. The Cardiovascular Health Study Cognition Study evaluated the determinants of the risk of dementia, diagnosed in 1998 99, among 3608 participants >65 years of age who had MRIof the brain in 1991 through 1994. In this cohort, there were 480 incident dementia cases, and 330 were diagnosed as AD. The CHS found that age, Modified Mini Mental State Examination scores, cerebral ventricular size, severity of white matter lesions, number of MRI identified infarcts, and the presence of the APOE 4 allele were predictors of dementia. This study showed the importance of controlling for neuroimaging findings the study of risk factors for dementia. Scores of global cognitive measures, the presence of the APOE 4 allele, and MRI of the brain were strong predictors of dementia and AD.","0 (Apolipoprotein E4);0 (Apolipoproteins E);Aged;Aged, 80 and over;Apolipoprotein E4;Apolipoproteins E/genetics;Brain/pathology;Cardiovascular Diseases/epidemiology;Cohort Studies;Dementia/ epidemiology/genetics;Depression/epidemiology;Female;Follow-Up Studies;Humans;Incidence;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Proportional Hazards Models;Risk Factors;United States/epidemiology","Kuller, L. H.",2003,Jul 16-31,,1,
3156,Risk factors for dementia in the Cardiovascular Health Study cognition study,"Several predispocitional and genetic factors are thought to be involved in the etiology of Alzheimer s disease (AD). Except for age, there is no consensus among researchers about the factors that can best predict AD. Some studies have found that, older women, cerebrovascular risk factors (hypertension, ischemic heart disease, diabetes mellitus), and the presence of the apolipoprotein E (APOE) 4 allele to be associated with the development of dementia and AD. However, there are a few large scale studies that have entered magnetic resonance imaging (MRI) findings in the analysis of risk factors for AD. The Cardiovascular Health Study Cognition Study evaluated the determinants of the risk of dementia, diagnosed in 1998 99, among 3608 participants >65 years of age who had MRIof the brain in 1991 through 1994. In this cohort, there were 480 incident dementia cases, and 330 were diagnosed as AD. The CHS found that age, Modified Mini Mental State Examination scores, cerebral ventricular size, severity of white matter lesions, number of MRI identified infarcts, and the presence of the APOE 4 allele were predictors of dementia. This study showed the importance of controlling for neuroimaging findings the study of risk factors for dementia. Scores of global cognitive measures, the presence of the APOE 4 allele, and MRI of the brain were strong predictors of dementia and AD.","Aged;Aged, 80 and over;Apolipoprotein E4;Apolipoproteins E/genetics;Brain/pathology;Cardiovascular Diseases/epidemiology;Cohort Studies;Dementia/ epidemiology/genetics;Depression/epidemiology;Female;Follow-Up Studies;Humans;Incidence;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Proportional Hazards Models;Risk Factors;United States/epidemiology","Kuller, L. H.",2003,Jul 16-31,,0,
3157,Contrast enhancement of brainstem tracts in Zellweger spectrum disorder: Evidence of inflammatory demyelination?,"Zellweger spectrum disorder, resulting from mutations in the peroxisome assembly mechanism, is genetically heterogeneous and phenotypically varied in disease characteristics and severity. In addition to manifesting gyration anomalies, affected individuals typically have white matter abnormalities ranging from hypomyelination in infancy to a more diffuse demyelinating leukoencephalopathy pattern in those surviving into childhood. Here we report a unique presentation in a 2 1/2-year-boy with acute neurological deterioration and MRI demonstrating avid contrast enhancement suggesting inflammatory demyelination in the brainstem. © 2011 Georg Thieme Verlag KG Stuttgart. New York.",steroid;article;brain stem;case report;child;contrast enhancement;demyelination;disorders of peroxisomal functions;follow up;human;male;mental deterioration;neurologic examination;nuclear magnetic resonance imaging;preschool child;priority journal;Zellweger syndrome,"Kulkarni, K. S.;Baranano, K. W.;Lin, D. D. M.;Raymond, G. V.",2011,,,0,
3158,How to assess the reliability of cerebral microbleed rating?,,Alzheimer disease;brain hemorrhage;clinical article;clinical assessment;controlled study;human;microbleed rating;neuroimaging;note;nuclear magnetic resonance imaging;rating scale;reliability,"Kuijf, H. J.;van Veluw, S. J.;Viergever, M. A.;Vincken, K. L.;Biessels, G. J.",2013,,,0,
3159,Efficient detection of cerebral microbleeds on 7.0 T MR images using the radial symmetry transform,"Cerebral microbleeds (CMBs) are commonly detected on MRI and have recently received an increased interest, because they are associated with vascular disease and dementia. Identification and rating of CMBs on MRI images may be facilitated by semi-automatic detection, particularly on high-resolution images acquired at high field strength. For these images, visual rating is time-consuming and has limited reproducibility. We present the radial symmetry transform (RST) as an efficient method for semi-automated CMB detection on 7.0 T MR images, with a high sensitivity and a low number of false positives that have to be censored manually. The RST was computed on both echoes of a dual-echo T2*-weighted gradient echo 7.0 T MR sequence in 18 participants from the Second Manifestations of ARTerial disease (SMART) study. Potential CMBs were identified by combining the output of the transform on both echoes. Each potential CMB identified through the RST was visually checked by two raters to identify probable CMBs. The scoring time needed to manually reject false positives was recorded. The sensitivity of 71.2% is higher than that of individual human raters on 7.0 T scans and the required human rater time is reduced from 30 to 2 minutes per scan on average. The RST outperforms published semi-automated methods in terms of either a higher sensitivity or less false positives, and requires much less human rater time.","Algorithms;Automatic Data Processing;Cerebral Arterial Diseases/diagnosis;Cerebral Hemorrhage/ diagnosis;False Positive Reactions;Female;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Normal Distribution;Observer Variation;Reproducibility of Results","Kuijf, H. J.;de Bresser, J.;Geerlings, M. I.;Conijn, M. M.;Viergever, M. A.;Biessels, G. J.;Vincken, K. L.",2012,Feb 1,10.1016/j.neuroimage.2011.09.061,0,
3160,Semi-Automated Detection of Cerebral Microbleeds on 3.0 T MR Images,"Cerebral microbleeds are associated with vascular disease and dementia. They can be detected on MRI and receive increasing attention. Visual rating is the current standard for microbleed detection, but is rater dependent, has limited reproducibility, modest sensitivity, and can be time-consuming. The goal of the current study is to present a tool for semi-automated detection of microbleeds that can assist human raters in the rating procedure. The radial symmetry transform is originally a technique to highlight circular-shaped objects in two-dimensional images. In the current study, the three-dimensional radial symmetry transform was adapted to detect spherical microbleeds in a series of 72 patients from our hospital, for whom a ground truth visual rating was made by four raters. Potential microbleeds were automatically identified on T2*-weighted 3.0 T MRI scans and the results were visually checked to identify microbleeds. Final ratings of the radial symmetry transform were compared to human ratings. After implementing and optimizing the radial symmetry transform, the method achieved a high sensitivity, while maintaining a modest number of false positives. Depending on the settings, sensitivities ranged from 65%-84% compared to the ground truth rating. Rating of the processed images required 1-2 minutes per participant, in which 20-96 false positive locations per participant were censored. Sensitivities of individual raters ranged from 39%-86% compared to the ground truth and required 5-10 minutes per participant per rater. The sensitivities that were achieved by the radial symmetry transform are similar to those of individual experienced human raters, demonstrating its feasibility and usefulness for semi-automated microbleed detection.",,"Kuijf, H. J.;Brundel, M.;de Bresser, J.;van Veluw, S. J.;Heringa, S. M.;Viergever, M. A.;Biessels, G. J.;Vincken, K. L.",2013,,10.1371/journal.pone.0066610,0,
3161,Imaging local brain function with emission computed tomography,"Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) was used to map local cerebral glucose utilization in the study of local cerebral function. This information differs fundamentally from structural assessment by means of computed tomography (CT). In normal human volunteers, the FDG scan was used to determine the cerebral metabolic response to controlled sensory stimulation and the effects of aging. After stroke, regional brain dysfunction is more extensive than had been suspected on the basis of CT scans. Cerebral metabolic patterns are distinctive among depressed and demented elderly patients. The FDG scan appears normal in the depressed patient, studded with multiple metabolic defects in patients with multiple infarct dementia, and in the patients with Alzheimer disease, metabolism is particularly reduced in the parietal cortex, but only slightly reduced in the caudate and thalamus. The caudate is markedly hypometabolic in Huntington disease, even in the absence of caudate atrophy, and possibly may be mildly hypometabolic even before the appearance of symptoms. The interictal FDG scan effectively detects hypometabolic brain zones that are sites of onset for seizures in patients with partial epilepsy, even though these zones usually appear normal on CT scans. The future prospects of PET are discussed.","Adolescent;Adult;Aged;Basal Ganglia Diseases/metabolism;Brain/ metabolism;Cerebrovascular Disorders/metabolism;Child, Preschool;Dementia/metabolism;Deoxyglucose/analogs & derivatives;Depressive Disorder/metabolism;Epilepsy/metabolism;Female;Fluorine;Fluorodeoxyglucose F18;Glucose/ metabolism;Humans;Male;Middle Aged;Radioisotopes;Tomography, Emission-Computed","Kuhl, D. E.",1984,Mar,10.1148/radiology.150.3.6607481,0,
3162,Abnormal cranial magnetic resonance imaging scans in sickle-cell disease: Neurological correlates and clinical implications,"Objective. - Eight asymptomatic patients with sickle-cell disease (SCD) with magnetic resonance imaging (MRI) abnormalities consistent with cerebral infarcts (group 1) and eight asymptomatic patients with SCD with normal MRI scans (group 2) were followed up to assess the neurological correlates and the clinical outcome. Design. - Patients in the two cohorts underwent clinical evaluations and xenon 133 regional cerebral blood flow (rCBF) studies within 1 month of the entry MRI. This study sequence was repeated up to 5 years later. Neuropsychological studies also were performed in six group 1 patients and eight group 2 patients at the end of the study. Setting. - The patients were recruited from the Comprehensive Sickle Cell Center at Columbia University, New York, NY. Patients. - All patients had SCD, hemoglobin SS, and normal findings on clinical evaluation at entry. The group 1 cohort had clinically silent MRI abnormalities consistent with cerebral infarction. The group 2 cohort was age matched to group 1 and had normal MRI studies. Interventions. - None. Main Outcome Measure. - The natural history of MRI abnormalities and the neurological correlates were assessed to determine the predictive value of subclinical MRI lesions as a risk factor for clinically apparent stroke. Results. - The mean duration of MRI follow-up was 3.7 years. In group 1, four patients (50%) demonstrated progressive MRI abnormalities and three patients (38%) became clinically symptomatic. In group 2, findings for all patients remained normal on clinical and radiological examination. Both groups had markedly elevated rCBF values. Individual rCBF differences correlated with the specific MRI abnormalities. The psychometric study results were similar in the two cohorts. Eighty-three percent of group 1 and 88% of group 2 patients had defective scores in one or more areas of cognitive functioning. Three patients met cognitive criteria for dementia. Conclusions. - Cranial MRI abnormalities have important prognostic implications even when detected in clinically asymptomatic patients. Cognitive abnormalities exist in patients with SCD even in the absence of MRI abnormalities or clinical stroke.",,"Kugler, S.;Anderson, B.;Cross, D.;Sharif, Z.;Sano, M.;Haggerty, R.;Prohovnik, I.;Hurlet-Jensen, A.;Hilal, S.;Mohr, J. P.;De Vivo, D. C.",1993,1993,,0,
3163,Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms,"Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. We explored risk factors for CSF discordance and escape in patients presenting with diverse neurological problems. Methods: HIV-infected adult patients undergoing diagnostic lumbar puncture (LP) at a single center between 2011 and 2015 were included in the analysis. Clinical and neuroimaging variables associated with CSF discordance/escape were identified using multivariate logistic regression. Results: One hundred forty-six patients with a median age of 45.3 (interquartile range [IQR], 39.6-51.5) years underwent 163 LPs. Median CD4 count was 430 (IQR, 190-620) cells/microL. Twenty-four (14.7%) LPs in 22 patients showed CSF discordance, of which 10 (6.1%) LPs in 9 patients represented CSF escape. In multivariate analysis, both CSF discordance and escape were associated with diffuse white matter signal abnormalities (DWMSAs) on cranial magnetic resonance imaging (adjusted odds ratio, 10.3 [95% confidence interval {CI}, 2.3-45.0], P = .007 and 56.9 [95% CI, 4.0-882.8], P = .01, respectively). All 7 patients with CSF escape (10 LPs) had been diagnosed with HIV >7 years prior to LP, and 6 of 6 patients with resistance data had documented evidence of drug-resistant virus in plasma. Conclusions: Among patients presenting with diverse neurological problems, CSF discordance or escape was observed in 15%, with treatment-experienced patients dominating the escape group. DWMSAs in HIV-infected individuals presenting with neurological problems should raise suspicion of possible CSF discordance/escape.","AIDS Dementia Complex/ pathology/virology;Adult;Aged;Aged, 80 and over;Cerebrospinal Fluid/ virology;Female;HIV Infections/ complications/virology;HIV-1/ isolation & purification;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies;Viral Load;White Matter/diagnostic imaging/ pathology;Young Adult;Csf;Hiv;neurocognitive impairment;viral escape;reservoir","Kugathasan, R.;Collier, D. A.;Haddow, L. J.;El Bouzidi, K.;Edwards, S. G.;Cartledge, J. D.;Miller, R. F.;Gupta, R. K.",2017,Apr 15,,0,
3164,Cerebral infarction during operation of the neck of the femur under epidural anesthesia: A report of two cases,"Cerebral infarction occurred during operation in two cases. An 83-year-old senile dementiated female underwent osteosynthesis with Ender pins under epidural anesthesia. Soon after Ender pins were inserted, her systolic blood pressure fell from 180 mmHg to 140 mmHg. The patient complained of chest pain and developed disturbed consciousness and the right hemiparesis. On the second postoperative day, CT scanning showed the infarction of a left middle cerebral artery region. A 93-year-old female was another patient. She underwent a cup arthroplasty of the right hip bone fracture. Soon after bone cement was applied, she developed a mental confusion and her blood pressure increased from 120/60 mmHg to 160/80 mmHg. CT scanning on the first postoperative day showed the infarction of a left middle cerebral artery region. Sudden changes in systolic blood pressure and changes of mental status are possible signs of cerebral infarction not to be neglected. If elderly patients with any episodes of cerebral function troubles would undergo operation of the hip fracture, it is necessary to pay a particular attention to possible cerebral infarction.",aged;article;brain infarction;brain perfusion;case report;female;femur;human;surgery,"Kudoh, A.;Shimodate, Y.;Ishihara, H.;Matsuki, A.",1991,,,0,
3165,White matter integrity and cortical metabolic associations in aging and dementia,"BACKGROUND: Studies show that white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigated how regional white matter integrity (measured as fractional anisotropy [FA]) relates to brain metabolism, to unravel the complex relationship between white matter changes and brain metabolism. OBJECTIVE: To elucidate the relationship between white matter integrity and gray matter metabolism using diffusion tensor imaging and fluorodeoxyglucose-positron emission tomography in a cohort of 16 subjects ranging from normal to demented (age, >55 years). METHODS: Mean FA values from white matter regions underlying the medial prefrontal, inferior-lateral prefrontal, parietal association, and posterior temporal areas and the corpus callosum were regressed with glucose metabolism (by positron emission tomography), using statistical parametric mapping (P < 0.005; voxel cluster, >100). Regional cerebral glucose metabolism was the primary outcome measure. According to our hypothesis, those hypometabolic cortical regions affected by Alzheimer's disease would correlate with a lower FA of associated tracks. RESULTS: Our data show inter-regional positive correlations between FA and gray matter metabolism for the prefrontal cortex, temporal, and parietal regions. Our results suggest that left prefrontal FA is associated with left temporal and parietal metabolism. Further, left posterior temporal FA correlated with left prefrontal metabolism. Finally, bilateral parietal FA correlated with bilateral temporal metabolism. CONCLUSIONS: These regions are associated with cognitive processes affected in Alzheimer's disease and cerebrovascular disease, suggesting a link with white matter degeneration and gray matter hypometabolism. Therefore, cortical function and white matter degeneration are related in aging and dementia.","Aged;Aged, 80 and over;Aging/ metabolism;Alzheimer Disease/complications/diagnosis/metabolism;Brain Mapping;Cerebral Cortex/ metabolism/radionuclide imaging;Cerebrovascular Disorders/complications/metabolism/pathology;Cohort Studies;Corpus Callosum/metabolism/pathology/radionuclide imaging;Dementia/metabolism/ pathology/radionuclide imaging;Diffusion Magnetic Resonance Imaging/methods;Female;Fluorodeoxyglucose F18;Humans;Image Processing, Computer-Assisted/methods;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Positron-Emission Tomography/methods;Retrospective Studies","Kuczynski, B.;Targan, E.;Madison, C.;Weiner, M.;Zhang, Y.;Reed, B.;Chui, H. C.;Jagust, W.",2010,Jan,10.1016/j.jalz.2009.04.1228,0,
3166,Compensatory shift of subcallosal area and paraterminal gyrus white matter parameters on DTI in patients with Alzheimer disease,"OBJECTIVE: Alzheimer disease is traditionally conceptualized as a disease of brain gray matter, however, studies with diffusion tensor imaging have demonstrated that Alzheimer disease also involves alterations in white matter integrity. We measured number of tracts, tracts length, tract volume, quantitative anisotropy and general fractional anisotropy of neuronal tracts in subcallosal area, paraterminal gyrus and fornix in patients with Alzheimer disease and healthy age-matched controls. Our hypothesis was that patients with Alzheimer disease should exhibit decrease in the integrity of these white matter structures that are crucial for semantic memory function. METHODS: For our study were selected 24 patients with confirmed Alzheimer disease diagnosis and 24 healthy controls (AD center, Department of Neurology, Charles University, Prague, Czech Republic). Statistically significant differences between the patients with Alzheimer disease and the control group were found both on the left and right fornices but only concerning the tract numbers and tract length. The subcallosal area and paraterminal gyrus showed statistically significant differences between the patients with Alzheimer disease and the control group, but only on the left side and only associated with the tract volume and quantitative anisotropy. CONCLUSION: Our explanation for these findings lies in the severe hippocampal atrophy (and subsequent loss of function) with compensatory hypertrophy of the subcallosal area and paraterminal gyrus neuronal fibers that occurs in Alzheimer s disease, as an adaptation to the loss of projection from the hippocampal formation via fornix.",,"Kuchtova, B.;Wurst, Z.;Mrzilkova, J.;Ibrahim, I.;Tintera, J.;Bartos, A.;Musil, V.;Kieslich, K.;Zach, P.",2017,Dec 27,,0,
3167,Linking white matter integrity loss to associated cortical regions using structural connectivity information in Alzheimer's disease and fronto-temporal dementia: the Loss in Connectivity (LoCo) score,"It is well known that gray matter changes occur in neurodegenerative diseases like Alzheimer's (AD) and fronto-temporal dementia (FTD), and several studies have investigated their respective patterns of atrophy progression. Recent work, however, has revealed that diffusion MRI that is able to detect white matter integrity changes may be an earlier or more sensitive biomarker in both diseases. However, studies that examine white matter changes only are limited in that they do not provide the functional specificity of GM region-based analysis. In this study, we develop a new metric called the Loss in Connectivity (LoCo) score that gives the amount of structural network disruption incurred by a gray matter region for a particular pattern of white matter integrity loss. Leveraging the relative strengths of WM and GM markers, this metric links areas of WM integrity loss to their connected GM regions as a first step in understanding their functional implications. The LoCo score is calculated for three groups: 18AD, 18 FTD, and 19 age-matched normal controls. We show significant correlations of the LoCo with the respective atrophy patterns in AD (R=0.51, p=2.2 x 10(-9)) and FTD (R=0.49, p=2.5 x 10(-8)) for a standard 116 region gray matter atlas. In addition, we demonstrate that the LoCo outperforms a measure of gray matter atrophy when classifying individuals into AD, FTD, and normal groups.","Alzheimer Disease/classification/*pathology;Atrophy/pathology;Cerebral Cortex/*pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/classification/*pathology;Humans;Image Interpretation, Computer-Assisted/*methods;Male;Middle Aged;Nerve Degeneration/pathology;Nerve Fibers, Myelinated/pathology;Neural Pathways/*pathology;Severity of Illness Index;Young Adult","Kuceyeski, A.;Zhang, Y.;Raj, A.",2012,Jul 16,10.1016/j.neuroimage.2012.03.039,0,
3168,The Network Modification (NeMo) Tool: elucidating the effect of white matter integrity changes on cortical and subcortical structural connectivity,"Accurate prediction of brain dysfunction caused by disease or injury requires the quantification of resultant neural connectivity changes compared with the normal state. There are many methods with which to assess anatomical changes in structural or diffusion magnetic resonance imaging, but most overlook the topology of white matter (WM) connections that make up the healthy brain network. Here, a new neuroimaging software pipeline called the Network Modification (NeMo) Tool is presented that associates alterations in WM integrity with expected changes in neural connectivity between gray matter regions. The NeMo Tool uses a large reference set of healthy tractograms to assess implied network changes arising from a particular pattern of WM alteration on a region- and network-wise level. In this way, WM integrity changes can be extrapolated to the cortices and deep brain nuclei, enabling assessment of functional and cognitive alterations. Unlike current techniques that assess network dysfunction, the NeMo tool does not require tractography in pathological brains for which the algorithms may be unreliable or diffusion data are unavailable. The versatility of the NeMo Tool is demonstrated by applying it to data from patients with Alzheimer's disease, fronto-temporal dementia, normal pressure hydrocephalus, and mild traumatic brain injury. This tool fills a gap in the quantitative neuroimaging field by enabling an investigation of morphological and functional implications of changes in structural WM integrity.","Alzheimer Disease/pathology;Brain/ pathology;Brain Injuries/pathology;Frontotemporal Dementia/pathology;Humans;Hydrocephalus, Normal Pressure/pathology;Nerve Net/ pathology;Neuroimaging/instrumentation/ methods;Reproducibility of Results;Software","Kuceyeski, A.;Maruta, J.;Relkin, N.;Raj, A.",2013,,10.1089/brain.2013.0147,0,
3169,The generation and validation of white matter connectivity importance maps,"Both the size and location of injury in the brain influences the type and severity of cognitive or sensorimotor dysfunction. However, even with advances in MR imaging and analysis, the correspondence between lesion location and clinical deficit remains poorly understood. Here, structural and diffusion images from 14 healthy subjects are used to create spatially unbiased white matter connectivity importance maps that quantify the amount of disruption to the overall brain network that would be incurred if that region were compromised. Some regions in the white matter that were identified as highly important by such maps have been implicated in strategic infarct dementia and linked to various attention tasks in previous studies. Validation of the maps is performed by investigating the correlations of the importance maps' predicted cognitive deficits in a group of 15 traumatic brain injury patients with their cognitive test scores measuring attention and memory. While no correlation was found between amount of white matter injury and cognitive test scores, significant correlations (r>0.68, p<0.006) were found when including location information contained in the importance maps. These tools could be used by physicians to improve surgical planning, diagnosis, and assessment of disease severity in a variety of pathologies like multiple sclerosis, trauma, and stroke.","Adolescent;Adult;Algorithms;Attention/physiology;Brain Injuries/ pathology/ psychology;Brain Mapping;Cognition Disorders/etiology/psychology;Diffusion Tensor Imaging;Disability Evaluation;Female;Glasgow Coma Scale;Humans;Image Processing, Computer-Assisted;Male;Memory/physiology;Middle Aged;Nerve Net/ injuries/ pathology;Neural Pathways/ pathology;Neuropsychological Tests;Probability;Reproducibility of Results;Young Adult","Kuceyeski, A.;Maruta, J.;Niogi, S. N.;Ghajar, J.;Raj, A.",2011,Sep 1,10.1016/j.neuroimage.2011.05.087,0,
3170,Proton magnetic resonance spectroscopy in patients with normal pressure hydrocephalus,"The objective of this prospective study was the application of proton magnetic resonance spectroscopy (1HMRS) in patients with normal pressure hydrocephalus (NPH) to determine the metabolite profile in the white matter next to left lateral ventricle and to assess the relationship of this profile with Evan's index. The study included 26 patients with NPH. Diagnosis of NPH was confirmed by clinical symptoms such as gait disturbance, dementia or urinary incontinence and CT study with ventricular enlargement. Ratios of NAA/Cr, Cho/Cr, Lac/Cr and mI/Cr from deep white matter were measured and compared with Evan's index and diameter of the IIIrd ventricle. Patients with hydrocephalus showed decreased ratios of N-acetylaspartate (NAA)/Cr (creatine), and increased ratios of Lac(lactate)/Cr in the white matter near the left frontal horn of the lateral ventricle compared with a well-matched control group. There was no correlation between NAA/Cr, Ch/Cr, Lac/Cr, mI (myo-Inositol)/Cr and Evan's index. A significant correlation was found between Lac/Cr and third ventricle diameter. A positive correlation was noted between Cho/Cr and dementia in patients with NPH. Our preliminary results of 1 H MRS support the idea that NPH is associated with white matter ischemia. Proton MRS is a very useful tool for evaluating major changes in metabolic levels in deep white matter in NPH patients.",,"Kubas, B.;Kulak, W.;Sobaniec, W.;Walecki, J.;Lewko, J.",2006,Nov 30,,0,
3171,Neuropsychological correlates of the proportional impact of white matter hyperintensities on mild to moderate dementia: the MRI 300 study,"BACKGROUND: White matter hyperintensities (WMH) increase cognitive impairment in patients with dementia. OBJECTIVE: We investigated the impact of WMH on the neuropsychological profiles in patients with mild to moderate dementia. METHODS: We consecutively recruited newly diagnosed patients with mild to moderate dementia across South Korea for 1 year. The participants completed neuropsychological tests, magnetic resonance imaging, and structured neurological evaluations. The patients were divided into 3 categories, i.e. minimal, moderate, and severe WMH groups, according to the proportional degree of WMH. RESULTS: 289 patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for the moderate group, and 50 (17.5%) for the severe group. Both advanced age and low general cognitive level were significant contributors to WMH in patients with dementia. After adjusting for age, the neuropsychological correlates of the proportional impact of WMH were frontal executive, language, and attention profiles. However, the only significant neuropsychological correlate was the recognition memory profile after adjusting for both age and general cognitive level simultaneously. CONCLUSION: The results suggest that the most significant neuropsychological profile impacting the burden of WMH in patients with mild to moderate dementia was the recognition memory profile, regardless of age and general cognitive function.","Activities of Daily Living;Age Factors;Aged;Alzheimer Disease/pathology/psychology;Brain/ pathology;Data Interpretation, Statistical;Dementia/ pathology/ psychology;Diagnostic and Statistical Manual of Mental Disorders;Educational Status;Executive Function;Female;Humans;Magnetic Resonance Imaging;Male;Memory;Mild Cognitive Impairment/ pathology/ psychology;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Republic of Korea","Ku, B. D.;Na, D. L.;Moon, S. Y.;Kim, S. Y.;Seo, S. W.;Cheong, H. K.;Park, K. W.;Park, K. H.;Lee, J. Y.;Cha, K. R.;Shim, Y. S.;Youn, Y. C.;Chung, C. S.;Kim, J. E.;Kang, H. Y.;Choi, S. H.;Han, S. H.",2011,,10.1159/000328624,0,
3172,Convection-enhanced delivery of M13 bacteriophage to the brain,"OBJECT: Recent studies indicate that M13 bacteriophage, a very large nanoparticle, binds to beta-amyloid and alpha-synuclein proteins, leading to plaque disaggregation in models of Alzheimer and Parkinson disease. To determine the feasibility, safety, and characteristics of convection-enhanced delivery (CED) of M13 bacteriophage to the brain, the authors perfused primate brains with bacteriophage. METHODS: Four nonhuman primates underwent CED of M13 bacteriophage (900 nm) to thalamic gray matter (4 infusions) and frontal white matter (3 infusions). Bacteriophage was coinfused with Gd-DTPA (1 mM), and serial MRI studies were performed during infusion. Animals were monitored for neurological deficits and were killed 3 days after infusion. Tissues were analyzed for bacteriophage distribution. RESULTS: Real-time T1-weighted MRI studies of coinfused Gd-DTPA during infusion demonstrated a discrete region of perfusion in both thalamic gray and frontal white matter. An MRI-volumetric analysis revealed that the mean volume of distribution (Vd) to volume of infusion (Vi) ratio of M13 bacteriophage was 2.3 +/- 0.2 in gray matter and 1.9 +/- 0.3 in white matter. The mean values are expressed +/- SD. Immunohistochemical analysis demonstrated mean Vd:Vi ratios of 2.9 +/- 0.2 in gray matter and 2.1 +/- 0.3 in white matter. The Gd-DTPA accurately tracked M13 bacteriophage distribution (the mean difference between imaging and actual bacteriophage Vd was insignificant [p > 0.05], and was -2.2% +/- 9.9% in thalamic gray matter and 9.1% +/- 9.5% in frontal white matter). Immunohistochemical analysis revealed evidence of additional spread from the initial delivery site in white matter (mean Vd:Vi, 16.1 +/- 9.1). All animals remained neurologically intact after infusion during the observation period, and histological studies revealed no evidence of toxicity. CONCLUSIONS: The CED method can be used successfully and safely to distribute M13 bacteriophage in the brain. Furthermore, additional white matter spread after infusion cessation enhances distribution of this large nanoparticle. Real-time MRI studies of coinfused Gd-DTPA (1 mM) can be used for accurate tracking of distribution during infusion of M13 bacteriophage.","Alzheimer Disease/pathology/therapy;Animals;Bacteriophage M13/ metabolism;Cerebral Infarction/pathology;Contrast Media;Convection;Disease Models, Animal;Frontal Lobe/ metabolism/ pathology;Gadolinium DTPA;Gliosis/pathology;Image Interpretation, Computer-Assisted;Macaca mulatta;Magnetic Resonance Imaging;Nanoparticles;Neurologic Examination;Parkinson Disease/pathology/therapy;Thalamus/ metabolism/ pathology","Ksendzovsky, A.;Walbridge, S.;Saunders, R. C.;Asthagiri, A. R.;Heiss, J. D.;Lonser, R. R.",2012,Aug,10.3171/2012.4.jns111528,0,
3173,Brain imaging in late-onset schizophrenia and related psychoses,"In this article we review the published studies on brain imaging in late-life psychoses, and present data from our study of magnetic resonance (MR) imaging of the brain in late-onset schizophrenia (LOS). MR images were obtained in 11 patients with late-onset schizophrenia (LOS), nine patients with probable Alzheimer's disease (AD), and nine normal controls comparable in age, gender, and education. Two of the LOS patients were excluded from further analysis due to the presence of diagnosable organic pathology (ie Alzheimer's disease and presence of a subaracnoid cyst). The MR images were subjectively rated for both degree of ventricular enlargement (VE) and degree of abnormal white matter hyperintensities (WMH) by an experienced, board certified neuroradiologist in a blind manner. No significant differences were found among the groups on degree of abnormal WMH. MR images of AD patients had a significantly greater degree of VE than normal controls, with LOS patients being intermediate. Our data, along with previous reports, suggest that a subset of patients with late-onset psychosis meet DSM-III-R criteria for LOS and have evidence of non-specific abnormalities in brain morphology on MR imaging, yet do not have clinical or",,"Krull, A. J.;Press, G.;Dupont, R.;Harris, M. J.;Jeste, D. V.",1991,1991,,0,
3174,Specific neuropsychological and neurophysiological dysfunctions of a patient with first-onset schizophrenia and comorbid white matter damage,"Background: Contemporary research on the neurobiological determinants of schizophrenia is focused on the role of white matter abnormalities, studied mainly at the cellular level using Diffusion Tensor Imaging. At the same time, there are few reports on the effects of white matter damage that can be visualized in a typical MRI scan, on the brain function of schizophrenic patients. The aim of this study was to identify the specific features of the neuropsychological and neurophysiological functioning of a female patient with first-onset schizophrenia and comorbid white matter damage, which discriminated her from a healthy control and from a patient with an identical psychiatric diagnosis, but having no structural brain changes seen in an MRI scan. Identification of those features may help understand the role of subcortical brain dysfunctions in the aetiology and clinical picture of schizophrenia. Case study: The investigation encompassed clinical, neuropsychological and neurophysiological assessment of two schizophrenic patients, of whom one had comorbid white matter damage imaged by structural MRI, and a healthy control. A number of areas of cognitive functioning were examined, including the speed of information processing and executive and memory functions. The study was conducted using EEG coherence analysis, power spectral density, and energy evaluation of neuronal activity with the Matching Pursuit algorithm. Results: The study showed that, despite the fact that there were no differences in the psychopathological pictures of the schizophrenic patients, the neuropsychological and neurophysiological differences between them were substantial and related to the profile of cognitive impairments and the specific features of the brain function of the patient with abnormalities in the white matter: that patient’s EEG showed discoherence in the anterior part of the brain, reduced diversity of the dominant frequency of neuronal activity, and pathologically increased energy parameters for low-frequency bands. Conclusions: Comorbidity of white matter damage with schizophrenia has a potentially significant effect on cerebral activity giving rise to specific information processing deficits. Further research in this area should be conducted with a view to determining biomarkers of mental diseases and improving the validity of clinical psychiatric diagnosis.",olanzapine;adult;article;Birchwood Insight Scale;brain function;California verbal learning test;case report;cognition;comorbidity;controlled study;electroencephalography;executive function;female;human;Letter Number Span test;MATRICS Consensus Cognitive Battery;mental deterioration;mental disease;neurophysiology;neuropsychological test;Positive and Negative Syndrome Scale;rating scale;Reading the Mind in the Eyes Test Revised Version;schizophrenia;semantics;speech disorder;treatment outcome;treatment response;Wechsler memory scale;white matter lesion;young adult,"Krukow, P.;Jonak, K.;Morylowska-Topolska, J.;Karakuła-Juchnowicz, H.",2017,,,0,
3175,Analysis of longitudinal diffusion-weighted images in healthy and pathological aging: An ADNI study,"BACKGROUND & NEW METHOD: The widely used framework of voxel-based morphometry for analyzing neuroimages is extended here to model longitudinal imaging data by exchanging the linear model with a linear mixed-effects model. The new approach is employed for analyzing a large longitudinal sample of 756 diffusion-weighted images acquired in 177 subjects of the Alzheimer's Disease Neuroimaging initiative (ADNI). RESULTS AND COMPARISON WITH EXISTING METHODS: While sample- and group-level results from both approaches are equivalent, the mixed-effect model yields information at the single subject level. Interestingly, the neurobiological relevance of the relevant parameter at the individual level describes specific differences associated with aging. In addition, our approach highlights white matter areas that reliably discriminate between patients with Alzheimer's disease and healthy controls with a predictive power of 0.99 and include the hippocampal alveus, the para-hippocampal white matter, the white matter of the posterior cingulate, and optic tracts. In this context, notably the classifier includes a sub-population of patients with minimal cognitive impairment into the pathological domain. CONCLUSION: Our classifier offers promising features for an accessible biomarker that predicts the risk of conversion to Alzheimer's disease. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how to apply/ADNI Acknowledgement List.pdf. Significance statement This study assesses neuro-degenerative processes in the brain's white matter as revealed by diffusion-weighted imaging, in order to discriminate healthy from pathological aging in a large sample of elderly subjects. The analysis of time-series examinations in a linear mixed effects model allowed the discrimination of population-based aging processes from individual determinants. We demonstrate that a simple classifier based on white matter imaging data is able to predict the conversion to Alzheimer's disease with a high predictive power.",Aging;Alzheimer's disease;Biomarker;Linear mixed-effects modeling;Longitudinal imaging;Voxel-based morphometry,"Kruggel, F.;Masaki, F.;Solodkin, A.;Alzheimer's Disease Neuroimaging, Initiative",2017,Feb 15,,0,
3176,Panencephalopathic type of Creutzfeldt-Jakob disease with primary extensive involvement of white matter,"The case of a 66-year-old woman with atypical Creutzfeld-Jakob disease (CJD) presents several peculiarities. Pathologic examination confirmed a rare CJD case with primary generalized spongiform changes of the white matter and only moderate, but typical changes of the gray matter. Besides an essentially typical clinical course, the patient developed temporary diplopia and vertical eye movement paralysis. Intoxication had been excluded. Isoelectric focusing revealed oligocloncal CSF-IgG. Magnetic resonance imaging studies showed periventricular accentuated flat and striped hyperintense structures. EEG had CJD-typical periodic 1/s synchronous discharges. This case illustrates for the first time that in panencephalopathic type of CJD the cerebral white matter can be involved primarily and more extensively than the gray matter.",,"Kruger, H.;Meesmann, C.;Rohrbach, E.;Muller, J.;Mertens, H. G.",1990,1990,,0,
3177,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Introduction. Fast and precise diagnostics of the disease from the large group of adult leukoencephalopathy is difficult but responsible job, because the outcome of the disease is very often determined by its name. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by the mutation of Notch 3 gene on chromosome locus 19p13. Beside the brain arterioles being the main disease targets, extracerebral small blood vessels are affected by the pathological process. Clinically present signs are recurrent ischemic strokes and vascular dementia. CADASIL in its progressive form shows a distinctive pattern of pathological changes on MRI of endocranium. The diagnosis is confirmed by the presence of granular osmiophilic material (GOM) in histopathological skin biopsies. Case reports. Two young adult patients manifested ischemic strokes of unknown etiology, cognitive deterioration, migraine and psychopathological phenomenology. MRI of endocranium pointed on CADASIL. Ultrastructural examination of skin biopsy proved the presence of GOM in the basal lamina and near smooth muscle cells of arteriole dermis leading to CADASIL diagnosis. The presence of GOM in histopathological preparation is 100% specific for CADASIL. The patients were not searched for mutation in Notch 3 gene on chromosome 19, because some other leukoencephalopathy was disregarded. Conclusion. Suggestive clinical picture, distinctive finding of endocranium MRI, the presence of GOM by ultrastructural examination of histopathological skin biopsies are sufficient to confirm CADASIL diagnosis.",albumin;corticosteroid;adult;alpha rhythm;anxiety;arm weakness;arteriole;artery resistance;article;basement membrane;blood brain barrier;brain ischemia;CADASIL;case report;cognitive defect;depression;dermis;diplopia;Doppler echography;dura mater;electroencephalogram;epileptic focus;evoked somatosensory response;evoked visual response;fatigue;female;granular osmiophilic material;headache;histopathology;human;hypesthesia;intelligence;male;migraine;mood;multiple sclerosis;nuclear magnetic resonance imaging;skin biopsy;smooth muscle fiber;tissue structure;vertebral artery;vertigo;walking difficulty;weakness;white matter,"Krsmanović, Z.;Dinčić, E.;Kostić, S.;Lačković, V.;Bajčetić, M.;Lačković, M.;Bošković, Z.;Raičević, R.",2011,,,0,
3178,Evaluation of reference regions for (R)-[(11)C]PK11195 studies in Alzheimer's disease and mild cognitive impairment,"Inflammation in Alzheimer's disease (AD) may be assessed using (R)-[(11)C]PK11195 and positron emission tomography. Data can be analyzed using the simplified reference tissue model, provided a suitable reference region is available. This study evaluates various reference regions for analyzing (R)-[(11)C]PK11195 scans in patients with mild cognitive impairment (MCI) and probable AD. Healthy subjects (n=10, 30+/-10 years and n=10, 70+/-6 years) and patients with MCI (n=10, 74+/-6 years) and probable AD (n=9, 71+/-6 years) were included. Subjects underwent a dynamic three-dimensional (R)-[(11)C]PK11195 scan including arterial sampling. Gray matter, white matter, total cerebellum and cerebrum, and cluster analysis were evaluated as reference regions. Both plasma input binding potentials of these reference regions (BP(PLASMA)) and corresponding reference region input binding potentials of a target region (BP(SRTM)) were evaluated. Simulations were performed to assess cluster analysis performance at 5% to 15% coefficient of variation noise levels. Reasonable correlations for BP(PLASMA) (R(2)=0.52 to 0.94) and BP(SRTM) (R(2)=0.59 to 0.76) were observed between results using anatomic regions and cluster analysis. For cerebellum white matter, cerebrum white matter, and total cerebrum a considerable number of unrealistic BP(SRTM) values were observed. Cluster analysis did not extract a valid reference region in 10% of the scans. Simulations showed that potentially cluster analysis suffers from negative bias in BP(PLASMA). Most anatomic regions outperformed cluster analysis in terms of absence of both scan rejection and bias. Total cerebellum is the optimal reference region in this patient category.","Adult;Aged;Algorithms;Alzheimer Disease/*radionuclide imaging;*Antineoplastic Agents/pharmacokinetics;Blood Volume/physiology;Cluster Analysis;Cognition Disorders/*radionuclide imaging;Computer Simulation;Female;Humans;Image Processing, Computer-Assisted;*Isoquinolines/pharmacokinetics;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Positron-Emission Tomography","Kropholler, M. A.;Boellaard, R.;van Berckel, B. N.;Schuitemaker, A.;Kloet, R. W.;Lubberink, M. J.;Jonker, C.;Scheltens, P.;Lammertsma, A. A.",2007,Dec,10.1038/sj.jcbfm.9600488,0,
3179,Thalamic venous infarction as a cause of subacute dementia,"The clinical picture of deep cerebral vein thromboses (DCVT) usually is acute, combining vigilance disorders, headaches, and focal neurologic deficit. The authors describe a patient who presented with isolated subacute dementia as the sole manifestation of DCVT. In the setting of subacute cognitive deficit, the diagnosis of DCVT must be considered when neuroimaging shows bilateral thalamic changes. Enhanced venous MR angiography is the noninvasive method of choice to ascertain the diagnosis.",adult;article;brain vein;case report;cerebral sinus thrombosis;clinical feature;cognitive defect;deep vein thrombosis;dementia;diagnostic imaging;disease course;human;magnetic resonance angiography;male;priority journal;thalamus,"Krolak-Salmon, P.;Montavont, A.;Hermier, M.;Milliery, M.;Vighetto, A.",2002,,,0,
3180,Total recovery after bilateral paramedian thalamic infarct,"Bilateral paramedian thalamic infarcts are characterised initially by the association of acute vigilance disorders and vertical gaze palsy, followed by persisting dementia with severe mnemic disturbance, global aspontaneity and apathy. We describe a patient with a dramatic neuropsychological recovery, confirmed by testing examination and completed by a cerebral metabolism study. The pathophysiology of this type of cognitive deficit is discussed. Copyright (C) 2000 S. Karger AG, Basel.",adult;apathy;article;brain blood flow;brain infarction;brain metabolism;case report;cognitive defect;dementia;gaze paralysis;human;male;neuropsychological test;nuclear magnetic resonance imaging;pathophysiology;priority journal;thalamus,"Krolak-Salmon, P.;Croisile, B.;Houzard, C.;Setiey, A.;Girard-Madoux, P.;Vighetto, A.",2000,,,0,
3181,Cerebral microbleedings and late stroke onset in a CADASIL family with rare deletion in exon 5 of the NOTCH3 gene,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASlL) is a rare hereditary non-atherosclerotic, non-amyloid systemic small vessel disease. Affected patients typically show migraine attacks, recurrent cerebral infarctions and a progressive cognitive decline eventually leading to subcortical vascular dementia. Psychiatric symptoms such as affective disorders appear in 40% of the mutation carriers. Seizures occur in about 10% of the patients. At the age of 40 years, leukencephalopathy is present in all mutation carriers, while a complete penetrance of clinical symptoms is usually observed up to the age of 60 years. CADASIL is caused by missense mutations in the NOTCH3 gene located on chromosome 19p13.1, We report on a German family with a very rare in-frame deletion in exon 5 of the NOTCH3 gene. In 2 of the 3 family members cerebral microhaemorrhages could be observed. One family member showed a late stroke onset with first cerebral ischaemic event at the age of 71 years. Characteristic and special features of the diagnostic evaluation and counselling of family members from three generations are discussed. The progression of leukencephalopathy with increasing age is demonstrated exemplarily by cerebral magnetic resonance imaging in 29-, 55- and 71-year-old mutation carriers. © Georg Thieme Verlag KG Stuttgart.",,"Krogias, C.;Meves, S.;Mönnings, P.;Andrich, J.;Köster, O.;Opherk, C.;Gold, R.",2008,October,,0,
3182,Magnetic resonance imaging of the caudate nuclei in depression: Preliminary observations,"A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3±17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2±1.6 cm(3)) compared with controls (6.2±1.7 cm(3)). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.",,"Krishnan, K. R. R.;McDonald, W. M.;Escalona, P. R.;Doraiswamy, P. M.;Na, C.;Husain, M. M.;Figiel, G. S.;Boyko, O. B.;Ellinwood, E. H.;Nemeroff, C. B.",1992,1992,,0,
3183,Congenital genetic inborn errors of metabolism presenting as an adult or persisting into adulthood: Neuroimaging in the more common or recognizable disorders,"Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or earlychildhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several neurodegenerative disorders of brain iron accumulation. Additionally, an arbitrary ""miscellaneous"" category of 5 recognizable disorders that may present in or persist into adulthood is summarized, which include megalencephalic leukoencephalopathy with subcortical cysts (megancephalic leukoencephalopathy with subcortical cysts or van der Knaap disease), polymerase-III gene defect (""4H syndrome""), childhood ataxia with central nervous system hypomyelination (""vanishing white matter disease""), striopallidodentate calcinosis (""Fahr disease""), and Cockayne syndrome. © 2014 Elsevier Inc.",,"Krishna, S. H.;McKinney, A. M.;Lucato, L. T.",2014,April,,0,
3184,The impact of magnetic resonance imaging-detected white matter hyperintensities on longitudinal changes in regional cerebral blood flow,"White matter hyperintensities are frequently detected on cranial magnetic resonance imaging (MRI) scans of older adults. Given the presumed ischemic contribution to the etiology of these lesions and the posited import of resting brain activity on cognitive function, we hypothesized that longitudinal changes in MRI-detected white matter disease, and its severity at a given time point, would be associated with changes in regional cerebral blood flow (rCBF) over time. We evaluated MRI scans and resting H(2)(15)O positron emission tomographic rCBF at baseline and after an average of 7.7-year follow-up in Baltimore Longitudinal Study of Aging participants without dementia. Differences in patterns of rCBF were evident at baseline and at follow-up between the group of subjects showing increased white matter disease over the 8-year interval compared with the group with stable white matter ratings. Furthermore, longitudinal changes over time in rCBF also differed between the two groups. Specifically, the group with progressive white matter abnormalities showed greater increase in the right inferior temporal gyrus/fusiform gyrus, right anterior cingulate, and the rostral aspect of the left superior temporal gyrus. Regions of greater longitudinal decrease in this group were evident in the right inferior parietal lobule and at the right occipital pole. Changes in white matter disease over time and its severity at any given time are associated significantly with both cross-sectional and longitudinal patterns of rCBF. The longitudinal increases may reflect cortical compensation mechanisms for reduced efficacy of interregional neural communications that result from white matter deterioration.",Aging;Blood Flow Velocity;Brain Diseases/ physiopathology/radiography;Cerebral Cortex/blood supply/ physiopathology/radiography;Cerebrovascular Circulation;Disease Progression;Female;Humans;Male;Retrospective Studies;Time Factors,"Kraut, M. A.;Beason-Held, L. L.;Elkins, W. D.;Resnick, S. M.",2008,Jan,10.1038/sj.jcbfm.9600512,0,
3185,Brain imaging and neuropsychology in late-onset dementia due to a novel mutation (R93C) of valosin-containing protein,"Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD, MIM 167320) is a recently identified autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) that affects muscle, bone and brain. Brain involvement and neuropsychological findings of IBMPFD have not been described in detail. A patient carried a novel heterozygous base pair change, 47832C>T, in the VCP gene that resulted in substitution of an arginine residue by cysteine at position 93 (R93C). He presented first with myopathy while bone involvement remained subclinical. The patient developed behavioral abnormalities in his 60s and showed frank personality change with fluent empty speech at the age of 74 years. This syndrome was best classified as semantic dementia. Magnetic resonance imaging disclosed slight but progressive cerebral atrophy with prominent callosal and frontal white matter loss. Positron emission tomography demonstrated glucose hypometabolism of the frontal and temporal lobes disproportionate to their structural involvement. This first comprehensive clinical and neuroimaging study in IBMPFD may raise the awareness among clinicians as well as basic scientists for this exemplary genetic model of dementia. ©2007 Dustri-Verlag Dr. K. Feistle.",,"Krause, S.;Göhringer, T.;Walter, M. C.;Schoser, B. G. H.;Reilich, P.;Linn, J.;Pöpperl, G. E.;Frölich, L.;Hentschel, F.;Lochmüller, H.;Danek, A.",2007,September/October,,0,
3186,Executive dysfunction in subcortical ischaemic vascular disease,"BACKGROUND: Executive dysfunction has been reported in patients with subcortical-frontal pathology, even in the absence of dementia. OBJECTIVE: This study was undertaken to determine if impairments in executive functioning could be found in non-demented patients with subcortical lacunes. METHODS: Cross sectional comparison between older control subjects (n=27) and non-demented patients with one or more subcortical lacunes (n=12). All participants were administered a neuropsychological test battery incorporating three measures of executive functioning, the Stroop interference test, California card sorting test, and the initiation-perseveration subtest of the Mattis dementia rating scale. RESULTS: No group differences were found on measures of recent verbal memory, language, or spatial ability. Normal controls performed better than patients with lacunes in visual memory. On the Stroop interference test, patients with lacunes performed as well as controls on the colour naming condition but slower on the interference condition. Patients with lacunes also generated fewer correct sorts on the California card sort test and achieved lower scores on the initiation-perseveration subtest. Executive measures were correlated with extent of white matter signal hyperintensity but not number of lacunes. CONCLUSION: Subcortical ischaemic vascular disease is associated with subtle declines in executive functioning and visual memory, even in non-demented patients. The pattern of cognitive impairment after subcortical lacunes is consistent with models of subcortical-frontal circuits.",Aged;Attention/*physiology;Brain Mapping;Cerebral Infarction/*diagnosis/physiopathology;Discrimination Learning/*physiology;Female;Frontal Lobe/physiopathology;Humans;Magnetic Resonance Imaging;Male;Nerve Net/physiopathology;*Neuropsychological Tests;Problem Solving/*physiology,"Kramer, J. H.;Reed, B. R.;Mungas, D.;Weiner, M. W.;Chui, H. C.",2002,Feb,,0,
3187,Forgetting in dementia with and without subcortical lacunes,"Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Analysis of Variance;Brain/pathology;Dementia, Multi-Infarct/*complications/pathology;Demography;Female;Humans;Magnetic Resonance Imaging/methods;Male;Memory/*physiology;Memory Disorders/*etiology/pathology;Mental Status Schedule;Neuropsychological Tests/statistics & numerical data;Retention (Psychology)/physiology","Kramer, J. H.;Mungas, D.;Reed, B. R.;Schuff, N.;Weiner, M. W.;Miller, B. L.;Chui, H. C.",2004,Feb,10.1080/13854040490507136,0,
3188,Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort,"OBJECTIVE: The aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardized visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population. METHODS: Patients with Alzheimer's disease (AD, n=58), mild cognitive impairment (MCI, n=141), subjective cognitive impairment (SCI, n=194) had clinical, MRI based WML severity and regional atrophy assessments, and routine resting EEG recording. Background activity (BA) and episodic and continuous abnormalities were assessed visually in EEG. RESULTS: WML (p=0.006) and atrophy in medial temporal regions (MTA) (p=<0.001) were associated with slower BA in all diagnoses. WML were associated in SCI with total episodic EEG abnormalities (p=0.03). CONCLUSIONS: EEG is associated with subclinical WML burden and cortical brain atrophy in a memory clinic population. SIGNIFICANCE: Even the standard visually assessed EEG can complement a memory clinic diagnostic workup.","Adult;Aged;Aged, 80 and over;Atrophy/diagnostic imaging/physiopathology;Cohort Studies;Electroencephalography/ trends;Female;Humans;Magnetic Resonance Imaging/ trends;Male;Memory Disorders/diagnostic imaging/physiopathology;Middle Aged;Temporal Lobe/ diagnostic imaging/ physiopathology;White Matter/ diagnostic imaging/ physiopathology;Cognitive impairment;Electroencephalography;Medial temporal atrophy;Visual analysis;White matter lesions","Kramberger, M. G.;Giske, K.;Cavallin, L.;Kareholt, I.;Andersson, T.;Winblad, B.;Jelic, V.",2017,Sep,,0,
3189,Bilateral paramedian thalamic infarct: A report of five cases,"Aim: The aim of this study is to analyze the incidence, etiology, symptoms, diagnostic process and treatment of bilateral thalamic infarct on the basis of our own experience. Case series: Five cases of bilateral paramedian thalamic stroke with different clinical manifestations are presented. In two patients the presence of artery of Percheron was detected. Comment: The bilateral thalamic infarct is an unusual and rare type of ischemic stroke. Due to the variety of symptoms, it may be difficult to diagnose without MR imaging. Symptoms may be transient, but frequently a persistent neurological deficit is observed. The thalamus is the “centre” for all impulses reaching the brain. It is involved in cognitive functions, emotional and motor responses. Therefore, impaired consciousness and behavioral changes are the main symptoms of thalamic stroke.",anticoagulant agent;antithrombocytic agent;adult;aged;anticoagulant therapy;aphasia;article;asthenia;atherosclerosis;atrial fibrillation;bilateral paramedian thalamic infarct;brain angiography;brain ischemia;carotid artery;cerebellum;clinical article;clinical feature;computed tomographic angiography;computer assisted tomography;consciousness disorder;electrocardiography;executive function;facial nerve paralysis;Glasgow coma scale;human;incidence;left hemisphere;magnetic resonance angiography;memory disorder;mesencephalon;middle aged;middle cerebral artery;mild cognitive impairment;National Institutes of Health Stroke Scale;neuroimaging;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;ophthalmoplegia;pyramidal tract;transthoracic echocardiography;vertebral artery,"Kozera-Strzelińska, D.;Nesteruk, M.;Holak-Puczyńska, A.;Nesteruk, T.;Dorobek, M.",2016,,10.1016/j.pin.2016.11.003,0,
3190,White matter hyperintensities in dementia of Alzheimer's type and in healthy subjects without cerebrovascular risk factors. A magnetic resonance imaging study,"T2-weighted (0.5 T) magnetic resonance images were used to study the prevalence of subcortical white matter hyperintensities (WMHIs) in 22 patients with dementia of Alzheimer's type (DAT), 20 age-matched older healthy control subjects, and 10 younger healthy control subjects. Exclusionary criteria for all groups included cerebrovascular risk factors. All subjects had Hachinski Ischemic Index scores of less than 2 and computed tomographic scans showing no infarct. The WMHIs were classified as periventricular WMHIs or deep WMHIs and graded 0 through 3 (0 indicated absent, and 3, severe). For the group with DAT and older control subjects, periventricular WMHIs and deep WMHIs were graded 2 or 3 in fewer than 17% and 27% of subjects, respectively, whereas in the younger control subjects, all ratings were grade 1 or less. Serum cholesterol and systolic blood pressure values, although within the normal range, were elevated significantly in older control subjects when compared with those in younger control subjects. No significant differences in WMHI ratings, blood pressure, cholesterol, or triglyceride levels were found between patients with DAT and age-matched control subjects. Systolic blood pressure levels correlated with the severity of periventricular WMHIs only in older control subjects. Age correlated with periventricular WMHIs and deep WMHIs within both the older control subjects and the patients with DAT. There was no significant correlation between WMHIs and the severity of dementia in the group with DAT. These results suggest that, in subjects screened for cerebrovascular risk factors, WMHIs are rare and occur with identical frequency in patients with DAT as in age-matched healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)",Aged;Alzheimer Disease/ pathology;Blood Glucose/analysis;Blood Pressure;Brain/ pathology;Cerebrovascular Disorders/etiology;Cholesterol/blood;Dementia/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors,"Kozachuk, W. E.;DeCarli, C.;Schapiro, M. B.;Wagner, E. E.;Rapoport, S. I.;Horwitz, B.",1990,Dec,,0,
3191,Diffusion tensor imaging of idiopathic normal pressure hydrocephalus: a voxel-based fractional anisotropy study,"Diffusion tensor imaging (DTI) using a 3.0 tesla magnetic resonance scanner was used to investigate white matter changes caused by idiopathic normal pressure hydrocephalus (INPH) in 10 patients diagnosed by clinical symptoms (gait disturbance, dementia, and/or urinary incontinence) and Evans index >0.3, and compared with findings for 10 age-matched controls (>/=60 years). Then, using a computer-automated method, fractional anisotropy (FA) brain maps were generated and finally transformed into the standard space. Voxel-based FA values within two regions of interests (ROIs), the forceps minor and corticospinal tracts, were then separately evaluated. Within each ROI, statistical comparisons of results from the INPH and control groups were performed. In addition, for INPH patients, grading scores for clinical symptoms and FA values were correlated. The forceps minor mean FA value was much smaller for the INPH group (0.504) than for the control group (0.631). The corticospinal tract mean FA value was slightly smaller for the INPH group (0.588) than for the control group (0.632). Additional analyses indicated that lower FA values within the forceps minor tended to be associated with clinical symptoms such as urinary incontinence and gait disturbance. Our findings indicate FA values decreased in the forceps minor of INPH patients. We also found that lower values were associated with severer clinical symptoms, implying that DTI techniques may be developed for more accurate diagnosis.","Aged;Aged, 80 and over;Anisotropy;Brain/ pathology/physiopathology;Case-Control Studies;Diffusion Tensor Imaging/ methods;Female;Humans;Hydrocephalus, Normal Pressure/complications/ pathology/physiopathology;Image Processing, Computer-Assisted/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neural Pathways/ pathology/physiopathology","Koyama, T.;Marumoto, K.;Domen, K.;Ohmura, T.;Miyake, H.",2012,,,0,
3192,White matter characteristics of idiopathic normal pressure hydrocephalus: a diffusion tensor tract-based spatial statistic study,"Using magnetic resonance-diffusion tensor imaging (DTI), we examined white matter changes within the brains of patients diagnosed with idiopathic normal pressure hydrocephalus (INPH). We analyzed data for 24 INPH patients who were presented with typical clinical symptoms (gait disturbance, dementia, and/or urinary incontinence) and Evans index > 0.3, and compared these with the control data from 21 elderly persons (>/= 60 years). DTI brain images were obtained with a 3T scanner. Fractional anisotropy (FA) brain maps were generated using a computer-automated method, and tract-based spatial statistics (TBSS) were then applied to compare the FA brain maps of the INPH and control groups in standard space. The TBSS data were further investigated using region-of-interest (ROI) analyses. ROIs were set within the corpus callosum, the posterior limb of the internal capsule (PLIC), and the cerebral peduncle in reference to a standard brain template. Compared with the control group, FA values in the INPH group were significantly lower in the corpus callosum and just significantly higher in the PLIC, but no significant differences were evident in the cerebral peduncle. The much lower FA values in the corpus callosum, but not the slightly higher FA values in the PLIC, were associated with more severe clinical symptoms such as gait disturbance. The lower FA values in the corpus callosum may offer a clue to solve the pathophysiology of INPH.","Aged;Aged, 80 and over;Anisotropy;Case-Control Studies;Corpus Callosum/pathology;Diffusion Tensor Imaging;Female;Humans;Hydrocephalus, Normal Pressure/ pathology;Internal Capsule/pathology;Male;Middle Aged;Tegmentum Mesencephali/pathology","Koyama, T.;Marumoto, K.;Domen, K.;Miyake, H.",2013,,,0,
3193,Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: A nested case-control study,"Background: Recent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD. Methods: A total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD. Results: Among CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710-13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010-0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein). Conclusions: The current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.",C reactive protein;cholesterol;hemoglobin A1c;high density lipoprotein;triacylglycerol;adult;albumin to globulin ratio;arterial stiffness;article;case control study;cholesterol blood level;controlled study;female;genetic linkage;genotype;Helicobacter pylori;hematological parameters;homeostasis;human;incidence;major clinical study;male;mental deterioration;Mini Mental State Examination;nuclear magnetic resonance imaging;protein homeostasis;pulse wave;risk assessment;risk factor;triacylglycerol blood level;white matter lesion,"Koyama, T.;Kuriyama, N.;Ozaki, E.;Matsui, D.;Watanabe, I.;Miyatani, F.;Kondo, M.;Tamura, A.;Kasai, T.;Ohshima, Y.;Yoshida, T.;Tokuda, T.;Mizuta, I.;Mizuno, S.;Yamada, K.;Takeda, K.;Matsumoto, S.;Nakagawa, M.;Mizuno, T.;Watanabe, Y.",2016,,10.1186/s12883-016-0776-z,0,
3194,Cerebral MR and CT imaging in Creutzfeldt-Jakob disease,"Magnetic resonance (MR) imaging and CT of three patients with Creutzfeldt-Jakob disease (CJD) showed bilateral cortical atrophy and no apparent white matter changes. Serial examinations revealed the progressive nature of the atrophy, findings compatible with the patient's clinical deterioration. At autopsy some white matter abnormalities were detected in one patient 6 months after MR imaging. The available data suggest that the white matter abnormalities, if present, develop during the final stage of CJD.",,"Kovanen, J.;Erkinjuntti, T.;Iivanainen, M.",1985,1985,,0,
3195,Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy,"Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.",,"Kovacs, G. G.;Ferrer, I.;Grinberg, L. T.;Alafuzoff, I.;Attems, J.;Budka, H.;Cairns, N. J.;Crary, J. F.;Duyckaerts, C.;Ghetti, B.;Halliday, G. M.;Ironside, J. W.;Love, S.;Mackenzie, I. R.;Munoz, D. G.;Murray, M. E.;Nelson, P. T.;Takahashi, H.;Trojanowski, J. Q.;Ansorge, O.;Arzberger, T.;Baborie, A.;Beach, T. G.;Bieniek, K. F.;Bigio, E. H.;Bodi, I.;Dugger, B. N.;Feany, M.;Gelpi, E.;Gentleman, S. M.;Giaccone, G.;Hatanpaa, K. J.;Heale, R.;Hof, P. R.;Hofer, M.;Hortobágyi, T.;Jellinger, K.;Jicha, G. A.;Ince, P.;Kofler, J.;Kövari, E.;Kril, J. J.;Mann, D. M.;Matej, R.;McKee, A. C.;McLean, C.;Milenkovic, I.;Montine, T. J.;Murayama, S.;Lee, E. B.;Rahimi, J.;Rodriguez, R. D.;Rozemüller, A.;Schneider, J. A.;Schultz, C.;Seeley, W.;Seilhean, D.;Smith, C.;Tagliavini, F.;Takao, M.;Thal, D. R.;Toledo, J. B.;Tolnay, M.;Troncoso, J. C.;Vinters, H. V.;Weis, S.;Wharton, S. B.;White, C. L.;Wisniewski, T.;Woulfe, J. M.;Yamada, M.;Dickson, D. W.",2016,1,,0,
3196,A robust method for extraction and automatic segmentation of brain images,"A new protocol is introduced for brain extraction and automatic tissue segmentation of MR images. For the brain extraction algorithm, proton density and T2-weighted images are used to generate a brain mask encompassing the full intracranial cavity. Segmentation of brain tissues into gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) is accomplished on a T1-weighted image after applying the brain mask. The fully automatic segmentation algorithm is histogram-based and uses the Expectation Maximization algorithm to model a four-Gaussian mixture for both global and local histograms. The means of the local Gaussians for GM, WM, and CSF are used to set local thresholds for tissue classification. Reproducibility of the extraction procedure was excellent, with average variation in intracranial capacity (TIC) of 0.13 and 0.66% TIC in 12 healthy normal and 33 Alzheimer brains, respectively. Repeatability of the segmentation algorithm, tested on healthy normal images, indicated scan-rescan differences in global tissue volumes of less than 0.30% TIC. Reproducibility at the regional level was established by comparing segmentation results within the 12 major Talairach subdivisions. Accuracy of the algorithm was tested on a digital brain phantom, and errors were less than 1% of the phantom volume. Maximal Type I and Type II classification errors were low, ranging between 2.2 and 4.3% of phantom volume. The algorithm was also insensitive to variation in parameter initialization values. The protocol is robust, fast, and its success in segmenting normal as well as diseased brains makes it an attractive clinical application.","Adult;Aged;Algorithms;Alzheimer Disease/ diagnosis;Brain/ pathology;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Normal Distribution;Phantoms, Imaging;Reference Values","Kovacevic, N.;Lobaugh, N. J.;Bronskill, M. J.;Levine, B.;Feinstein, A.;Black, S. E.",2002,Nov,,0,
3197,Acute bilateral thalamic infarction as a cause of acute dementia and hypophonia after occlusion of the artery of Percheron,"The thalami of the human brain obtain their blood supply from many perforating arteries, which exhibit complex distribution and many variations. One rare variation is the artery of Percheron that supplies the paramedian thalami bilaterally. This artery arises from the first segment of the posterior cerebral artery and gives rise to bilateral medial thalamic perforants. Occlusion of the artery of Percheron none rarely results in bilateral thalamic and mesencephalic infarctions. We describe the case of a 38-year-old male patient with a presumed occlusion of this artery in which",,"Koutsouraki, E.;Xiromerisiou, G.;Costa, V.;Baloyannis, S.",2009,15,,0,
3198,CADASIL presenting with spontaneous intracerebral hemorrhage: Report of a case and description of the first family in Northern Greece,"Introduction: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), the most common inherited cause of stroke and dementia in adults, has been described in six Greek families. Common presenting manifestations include migraine with aura, brain ischemia, mood disorders and cognitive decline. Spontaneous intracerebral hemorrhage (SICH) rarely occurs in CADASIL and only exceptionally as the first clinical manifestation. Case description:We have previously reported the sixth Greek family with CADASIL and in particular, two brothers in whom the genetic testing documented a classic mutation of the NOTCH3 gene (Arg169Cys). In this report, we describe the 30-year-old son of the second brother, who suffered a thalamic SICH as the presenting manifestation of CADASIL, in the absence of arterial hypertension or antiplatelet drug use. Conclusion: Patients with acute subcortical infarcts, leukoencephalopathy, a history of migraine, mood disorders, and dementia, should always raise the suspicion of CADASIL. However, a SICH, even in the absence of classical risk factors for hemorrhage, is possible and should not exclude the diagnosis of CADACIL.",Notch3 receptor;adult;article;brain hemorrhage;CADASIL;case report;computer assisted tomography;family history;gene;gene mutation;genetic screening;Greece;hand paresthesia;headache;hemiparesis;human;lacunar stroke;leukoencephalopathy;male;middle aged;multiple sclerosis;mutational analysis;neuroimaging;NOTCH3 gene;nuclear magnetic resonance imaging;smoking,"Koutroulou, I.;Karapanayiotides, T.;Grigoriadis, N.;Karacostas, D.",2016,,,0,
3199,Acute onset vascular dementia with bi-thalamic infarct in an HIV-positive subject,"Objective: Rare co-existance of disease or patholog Background: Bi-thalamic infarctions are rare and marked by clinical polymorphism. Their association with HIV has never been reported. Case Report: We report a 51-year-old right-handed man with no medical history, who presented an acute onset vascular dementia associated with an antero-retrograde amnesia, a word-finding difficulty, and a dysexecutive syndrome. The CT scan was normal. Brain MRI revealed a paramedian and bi-thalamic infarction, evoking an occlusion of the Percheron artery. The electrocardiogram, transthoracic and transesophageal cardiac ultrasound, and Doppler echo of cervical arteries gave normal results. The biological work-up revealed a positive serology to HIV1. The patient was lost to follow-up and was reported dead 2 months later from an unknown cause. Conclusions: This case illustrates the need to perform an HIV serology in the presence of a bi-thalamic infarction with no obvious cause, particularly in a young subject.",lysine acetylsalicylate;adult;article;asthenia;case report;cause of death;clinical article;consultation;disorientation;face asymmetry;follow up;human;Human immunodeficiency virus infection;insomnia;male;middle aged;Mini Mental State Examination;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;slurred speech;thalamus,"Kouassi, L. K.;Doumbia-Ouattara, M.",2017,,10.12659/ajcr.905297,0,
3200,Neuropathologic correlates of regional brain volumes in a community cohort of older adults,"The objective of this work was 2-fold: to generate macrostructural brain signatures of age-related neuropathologies in a community cohort of older adults and to determine the contribution of brain macrostructure to the variation in antemortem cognition after accounting for the contributions of neuropathologies and demographics. Cerebral hemispheres from 165 participants of 2 cohort studies of aging were imaged with magnetic resonance imaging ex vivo (mean age at death = 90 years; standard deviation = 6 years). The volumes of white matter and 42 gray matter regions were measured. The same hemispheres also underwent neuropathologic examination. Alzheimer's disease pathology was negatively associated with volumes of mainly temporal, frontal, and parietal gray matter regions, and with total white matter volume (p < 0.05, false discovery rate-corrected). A negative association was also detected between hippocampal sclerosis and volumes of the hippocampus, as well as other temporal and frontal gray matter regions (p < 0.05, false discovery rate-corrected). The volume of mainly medial temporal lobe regions explained an additional 5%-6% of the variation in antemortem cognition, above and beyond what was explained by neuropathologies and demographics.",,"Kotrotsou, A.;Schneider, J. A.;Bennett, D. A.;Leurgans, S. E.;Dawe, R. J.;Boyle, P. A.;Golak, T.;Arfanakis, K.",2015,Oct,10.1016/j.neurobiolaging.2015.06.025,0,
3201,Mutations of the Notch3 gene in non-Caucasian patients with suspected CADASIL syndrome,"The Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations in familial cases with vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families, which were selected on the basis of magnetic resonance imaging findings and positive family history. We identified three different missense mutations in 5 patients from 4 families. Two (Arg90Cys and Arg133Cys) are the same as previously reported in Caucasian patients, the other (Cys174Phe) is a novel mutation causing a loss of a cysteine in epidermal-growth-factor-like repeats of Notch3. These data indicate that the CADASIL Notch3 mutations were found in approximately 35% of familial cases with leukoencephalopathy, suggesting genetic heterogeneity of the disease. Copyright © 2001 S. Karger AG, Basel.",,"Kotorii, S.;Takahashi, K.;Kamimura, K.;Nishio, T.;Arima, K.;Yamada, H.;Uyama, E.;Uchino, M.;Suenaga, A.;Matsumoto, M.;Kuchel, G.;Rouleau, G. A.;Tabira, T.",2001,2001,,0,
3202,A case of CADASIL in early stage,"We report a 26-year-old woman who showed recurrent migrainous attacks and convulsions since her childhood. Neurological examination revealed no focal abnormality except mental retardation (MR). T2-and fluidattenuated inversion-recovery (FLAIR)-weighted brain MRI revealed apparent high intensities in the deep subcotical white matter. Ultrastructual studies revealed an abnormal deposition of granular osmiophilic materials (GOM) on the surface of vascular smooth muscle cells in dermis, Her mother developed reccurent strokes without risk factor since age 41. A heterozygosis Arg133Cys mutation of Notch 3 gene has already presented in patient and her mother. This case might be an early stage in CADASIL before stroke onset and suggested that systemic vasculopathy was presented in this stage, The correlation between MR and phenotype of CADASIL were unclear.",adult;article;brain infarction;CADASIL;case report;convulsion;female;gene mutation;human;leukoencephalopathy;mental deficiency;migraine;nuclear magnetic resonance imaging;risk factor;cerebrovascular accident,"Kotorii, S.;Sakae, N.;Yamada, N.;Yamanaka, H.;Fujii, N.;Nakashima, Y.",2001,,,0,
3203,A case of CADASIL showing spontaneous subcortical hemorrhage with a novel mutation of Notch3 gene,"The case of a 72-year-old demented woman having episodes of strokes without any risk factors for cardiovascular disease is reported. Her elder brother and sister have also had stroke episodes since their middle age. She experienced hallucinations, delusions, and recurrent headaches since the age of 55. She has gradually developed gait disturbance and cognitive impairment. Brain MRI revealed extensive leukoaraiosis and multiple lacunar infarcts in the deep white matter and brainstem. Repeated MRI incidentally disclosed fresh hemorrhage in the dorsal subcortical temporal lobe, which appeared to be asymptomatic. Anti-platelet agents were not used during disease progression. We detected G975C mutation of the Notch3 gene and diagnosed our patient's disease as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This report suggests that arteriopathy of CADASIL could cause a hemorrhagic process, indicating that, in such a case, routine administration of anti-platelet agent to prevent recurrent ischemic stroke is not recommended.",antithrombocytic agent;Notch3 receptor;aged;article;brain cortex;brain hemorrhage;CADASIL;cardiovascular risk;case report;clinical feature;female;gene mutation;human;leukoaraiosis;nuclear magnetic resonance imaging,"Kotorii, S.;Goto, H.;Kondo, T.;Matsuo, H.;Takahashi, K.;Shibuya, N.",2006,,,0,
3204,A case of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy) with Notch3 (Arg169Cys) mutation and typical granular osmiophilic materials in peripheral small arteries,"We report a 64-year-old Japanese woman with recurrent ischemic strokes and progressive dementia without any cardiovascular risk factors. Her first stroke was at 45 years old, and she has a family history of ischemic strokes compatible with an autosomal dominant trait. Marked leukoaraiosis and multiple lacunar infarcts were shown on brain MR images, and no atherosclerotic changes were observed in her extra- and intra-cranial arteries by cervical arterial echography and intracranial MR angiography. Excluded other inherited or metabolic diseases causing leukodystrophy by examination of her blood samples, her disease was diagnosed as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lekoencephalopathy). We demonstrated granular osmiophilic materials (GOM) on the wall of small arteries from a biopsied peripheral nerve tissue specimen and detected a mutation Arg169Cys of Notch 3 gene. Many CADASIL patients have been reported and over 28 kinds of mutations of the Notch 3 were identified in western countries, while few CADASIL patients have been reported in Japanese people. Among them, eleven CADASIL families have been reported and only five mutations (Arg133Cys, Cys174Phe, Arg213Lys, Arg90Cys and Arg141Cys) have been determined so far. The mutation of Notch 3 in our patient was determined as Arg169Cys, and this is the first report on a Japanese patient with CADASIL due to this mutation.",,"Kotani, N.;Hara, H.;Fujimura, H.;Miyashita, T.;Miyaguchi, K.;Tabira, T.",2004,April/May,,0,
3205,Educational attainment and motor burden in Parkinson's disease,"OBJECTIVE: Greater educational attainment is a protective factor for neurodegenerative dementias. If education earlier in life leads to greater cerebral reserve, it may play a similar protective role in Parkinson's disease (PD). METHODS: We conducted a cross-sectional clinical imaging study of 142 subjects with PD. All subjects underwent [(11)C]dihydrotetrabenazine PET to confirm nigrostriatal dopaminergic denervation and brain MRI to estimate adjusted cortical gray matter volume (GMV). RESULTS: After adjusting for possible confounders, including cognitive and dopaminergic covariates, as well as nonspecific neurodegeneration covariates (age, disease duration, and total adjusted cortical GMV), lower years of education remained a significant predictor of higher total MDS-UPDRS motor score (t = -3.28; P = 0.001). Education level associated inversely with white matter (WM) hyperintensities in a post-hoc analysis (n = 83). CONCLUSIONS: Higher educational attainment is associated with lower severity of motor impairment in PD. This association may reflect an extranigral protective effect upon WM integrity.",,"Kotagal, V.;Bohnen, N. I.;Muller, M. L.;Koeppe, R. A.;Frey, K. A.;Langa, K. M.;Albin, R. L.",2015,Jul,10.1002/mds.26272,0,
3206,Imaging changes associated with cognitive abnormalities in Parkinson's disease,"The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre- and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD.","Aged;Analysis of Variance;Cerebral Cortex/ pathology;Cognition Disorders/ complications/ pathology;Diffusion Tensor Imaging;Executive Function;Female;Gray Matter/pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests;Parkinson Disease/ complications/ pathology;Psychiatric Status Rating Scales;White Matter/pathology","Koshimori, Y.;Segura, B.;Christopher, L.;Lobaugh, N.;Duff-Canning, S.;Mizrahi, R.;Hamani, C.;Lang, A. E.;Aminian, K.;Houle, S.;Strafella, A. P.",2015,Jul,10.1007/s00429-014-0785-x,0,
3207,Regional cerebral blood flow and periventricular hyperintensity in silent cerebral infarction--comparison with multi-infarct dementia,"In order to investigate relationship between regional cerebral blood flow (rCBF) and the white matter lesions on MRI in silent cerebral infarction, we quantitatively measured rCBF by 123I-IMP autoradiography method (IMP ARG method) and single photon emission tomography (SPECT) in 36 patients with silent cerebral infarction (SCI group), 22 patients with multi-infarct dementia (MID group), and 16 control subjects without periventricular hyperintensity (PVH) and lacunar infarction on MRI (CL group). Regions of interest (ROIs) on rCBF images were set in the frontal (F), temporal (T), parietal (P), occipital (O) cortex, and the cerebral white matter (W). The severity of PVH on MRI T2-weighted image was divided into four grades (grade 0-3). Our results: 1) Though the frequency of hypertension was significantly higher in SCI group and MID group compared with CL group, no significant difference was seen in the mean age among these three groups. 2) rCBF in the white matter and cerebral cortices except the occipital cortex in SCI group was significantly low compared with CL group (gamma CBFSCI/gamma CBFCL: W 0.87, F 0.87, P 0.88, O 0.92). 3) rCBF in the white matter and cerebral cortices, especially in the white matter and frontal cortex, in MID group was significantly low compared with SCI group (gamma CBFMID/gamma CBFCL: W 0.69, F 0.71, T 0.74, P 0.75, O 0.81). 4) The mean grade of PVH in MID group was significantly higher that that in SCI group (SCI 1.1 vs MID 2.5). 5) The severity of PVH was significantly correlated with each rCBF in the white matter and cerebral cortices, especially in the white matter and frontal cortex. Our findings suggest that the quantitative measurement of rCBF by IMP ARG method is useful for the follow-up study in the patients with silent cerebral infarction as well as the evaluation of the severity of PVH on MRI.","Aged;Aged, 80 and over;Amphetamines;Autoradiography/methods;Brain/blood supply/pathology;Cerebral Infarction/ diagnosis/pathology/physiopathology;Dementia, Multi-Infarct/ diagnosis/pathology/physiopathology;Female;Follow-Up Studies;Humans;Iodine Radioisotopes;Iofetamine;Magnetic Resonance Imaging;Male;Middle Aged;Regional Blood Flow;Tomography, Emission-Computed, Single-Photon","Koshi, Y.;Kitamura, S.;Nagazumi, A.;Tsuganesawa, T.;Terashi, A.",1996,Jun,,0,
3208,"Timed Up and Go test, atrophy of medial temporal areas and cognitive functions in community-dwelling older adults with normal cognition and mild cognitive impairment","Aim This study aimed to ascertain if performance on the Timed Up and Go (TUG) test is associated with indicators of brain volume and cognitive functions among community-dwelling older adults with normal cognition or mild cognitive impairment. Methods Participants were 80 community-dwelling older adults aged 65–89 years (44 men, 36 women), including 20 with mild cognitive impairment. Participants completed the TUG and a battery of cognitive assessments, including the Mini-Mental State Examination (MMSE), the Logical Memory I and II (LM-I, LM-II) subtests of the Wechsler Memory Scale-Revised; and the Trail Making Test A and B (TMT-A, TMT-B). Bilateral, right- and left-side medial temporal area atrophy as well as whole gray and white matter indices were determined with the Voxel-based Specific Regional Analysis System for Alzheimer's Disease. We divided participants into three groups based on TUG performance: “better” (≤ 6.9 s); “normal” (7–10 s); and “poor” (≥ 10.1 s). Results Worse TMT-A and TMT-B performance showed significant independent associations with worse TUG performance (P < 0.05, P < 0.01 for trend, respectively). After adjusting for covariates, severe atrophy of bilateral, right-, and left-side medial temporal areas were significantly independently associated with worse TUG performance (P < 0.05 for trend). However, no significant associations were found between MMSE, LM-I, LM-II, whole gray and white matter indices, and TUG performance. Conclusions Worse TUG performance is related to poor performance on TMT-A and TMT-B, and is independently associated with severe medial temporal area atrophy in community-dwelling older adults.",aged;article;brain atrophy;brain size;cognition assessment;controlled study;cross-sectional study;disease association;disease severity;female;gray matter;human;image analysis;Logical memory I;Logical memory II;major clinical study;male;memory assessment;mild cognitive impairment;Mini Mental State Examination;nuclear magnetic resonance imaging;priority journal;sensitivity and specificity;Timed Up and Go test;trail making test;very elderly;Wechsler memory scale;white matter,"Kose, Y.;Ikenaga, M.;Yamada, Y.;Morimura, K.;Takeda, N.;Ouma, S.;Tsuboi, Y.;Yamada, T.;Kimura, M.;Kiyonaga, A.;Higaki, Y.;Tanaka, H.",2016,,10.1016/j.exger.2016.09.019,0,
3209,Familial presenile dementia with CJD-like lesions: Preliminary results,"A case of an unknown type of familial presenile dementia is reported. The patient was a 56-year-old female, whose main clinical symptom was a gradually progressive dementia over 16 years. She had no myoclonus or periodic synchronous discharge in the EEG. The CT scans revealed marked cerebral atrophy with prominent atrophy of the cerebral white matter. One of her sisters is thought to suffer from the same disease, and is now in an apallic state. The patient was clinically diagnosed as having familial Alzheimer's disease. The neuropathological features consisted of severe cerebral cortical degeneration with conspicuous proliferation of gemistocytic astrocytes as well as severe cerebral white matter degeneration. These cerebral lesions are most similar to those of the panencephalopathic type of Creutzfeldt-Jakob's disease (CJD). However, our case differs from it in that the cerebellar degeneration was very mild. Transmission experiments of frozen tissue from the patient into animals are being tried. The neurochemical data suggested cholinergic deficits.",neurotransmitter;autopsy;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;histology;human;presenile dementia,"Kosaka, K.;Arai, H.;Ikeda, K.",1985,,,0,
3210,"The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis","Background: Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients. Method: The study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals. Results: One known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria. Conclusions: These findings have significantly expanded the number of FOXG1mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the FOXG1 syndrome.",,"Kortüm, F.;Das, S.;Flindt, M.;Morris-Rosendahl, D. J.;Stefanova, I.;Goldstein, A.;Horn, D.;Klopocki, E.;Kluger, G.;Martin, P.;Rauch, A.;Roumer, A.;Saitta, S.;Walsh, L. E.;Wieczorek, D.;Uyanik, G.;Kutsche, K.;Dobyns, W. B.",2011,June,,0,
3211,"The clinical, neuroanatomical, and neuropathologic phenotype of TBK1-associated frontotemporal dementia: A longitudinal case report","INTRODUCTION: Mutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear. METHODS: We performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually over a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem. RESULTS: The patient presented at the age of 64 years with an 18-month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57 years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72 years and postmortem showed TDP-43 type A pathology but with an unusual novel feature of numerous TAR DNA-binding protein 43 (TDP-43)-positive neuritic structures at the cerebral cortex/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other TBK1 mutation cases. DISCUSSION: TBK1-associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next-generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis.",Frontotemporal dementia;Neurogenetics;Neuropathology;Tbk1,"Koriath, C. A.;Bocchetta, M.;Brotherhood, E.;Woollacott, I. O.;Norsworthy, P.;Simon-Sanchez, J.;Blauwendraat, C.;Dick, K. M.;Gordon, E.;Harding, S. R.;Fox, N. C.;Crutch, S.;Warren, J. D.;Revesz, T.;Lashley, T.;Mead, S.;Rohrer, J. D.",2017,,,0,
3212,Brain aging in very old men with type 2 diabetes: The Honolulu-Asia Aging Study,"OBJECTIVE - Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study was to investigate the association between type 2 diabetes and markers of brain aging on magnetic resonance images, including infarcts, lacunes, and white matter hyperintensities as markers of vascular damage and general and hippocampal atrophy as markers of neurodegeneration in Japanese-American men born between 1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study. RESEARCH DESIGN AND METHODS - Prevalent and incident dementia was assessed. Associations between magnetic resonance imaging markers and diabetic status were estimated with logistic regression, controlling for sociodemographic and other vascular factors. RESULTS - The prevalence of type 2 diabetes in the cohort is 38%. Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds ratio [OR] 1.6 [95% CI 1.0-2.6]) and hippocampal atrophy (1.7 [0.9-2.9]). The risk for both hippocampal atrophy and lacunes/infarcts was twice as high in subjects with compared with those without type 2 diabetes. Among the group with type 2 diabetes, those with the longest duration of diabetes, those taking insulin, and those with complications had relatively more pathologic brain changes. CONCLUSIONS - There is evidence that older individuals with type 2 diabetes have an elevated risk for vascular brain damage and neurodegenerative changes. These pathological changes may be the anatomical basis for an increased risk of cognitive impairment or dementia in type 2 diabetes. © 2006 by the American Diabetes Association.",,"Korf, E. S. C.;White, L. R.;Scheltens, P. H.;Launer, L. J.",2006,October,,0,
3213,Midlife blood pressure and the risk of hippocampal atrophy: The Honolulu Asia aging study,"Hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and neuritic plaques of Alzheimer disease. However, the hippocampus is vulnerable to global ischemia, which may lead to atrophy. We investigated the association of midlife blood pressure (BP) and late-life HA in a sample of Japanese-American men born between 1900 and 1919. BP was measured on 3 occasions between 1965 and 1971. In 1994 to 1996 a subsample underwent magnetic resonance imaging (MRI) of the brain. Hippocampal volume was estimated by manually drawing regions of interest on relevant scan slices;",,"Korf, E. S. C.;White, L. R.;Scheltens, P.;Launer, L. J.",2004,July,,0,
3214,Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment,"BACKGROUND: Although detailed volumetric MRI assessment of medial temporal lobe atrophy (MTA) can predict dementia in patients with mild cognitive impairment (MCI), it is not easily applied to routine clinical practice. OBJECTIVE: To test the predictive accuracy of visually assessed MTA in MCI patients using a standardized visual rating scale. METHODS: Seventy-five MCI patients (mean age 63 years) underwent a coronal three-dimensional magnetization-prepared rapid gradient echo brain MRI sequence. MTA was rated visually using a 5-point rating scale. RESULTS: The mean follow-up period for the cohort was 34 months. At follow-up, 49% of the enrolled MCI patients fulfilled criteria for dementia. MTA assessed using a standardized visual rating scale was significantly associated with dementia at follow-up, with a hazard ratio of 1.5 for every point increase in atrophy score (p < 0.001) and of 3.1 for the presence of atrophy based on the dichotomized atrophy score (p = 0.003). The predictive accuracy of visually assessed MTA was independent of age, gender, education, Mini-Mental State Examination score, Clinical Dementia Rating Sum of Boxes score, Verbal Delayed Recall, and the presence of hypertension, depression, the APOE epsilon4 allele, and white matter hyperintensities. CONCLUSIONS: Visual assessment of MTA on brain MRI using a standardized rating scale is a powerful and independent predictor of conversion to dementia in relatively young MCI patients. As overlap existed in MTA scores between patients with and without dementia at follow-up, the results should be interpreted in the light of the odds for the individual patient.","Aged;Apolipoproteins E/genetics;Atrophy;Cognition Disorders/genetics/*pathology/psychology;Dementia/epidemiology/*pathology;Disease Progression;Educational Status;Female;Follow-Up Studies;Genotype;Humans;Imaging, Three-Dimensional;*Magnetic Resonance Imaging;Male;Memory Disorders/pathology/psychology;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Prospective Studies;Temporal Lobe/*pathology","Korf, E. S.;Wahlund, L. O.;Visser, P. J.;Scheltens, P.",2004,Jul 13,,0,
3215,"Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease?","BACKGROUND: Vascular factors are recognized as important risk factors for Alzheimer's disease, although it is unknown whether these factors directly lead to the typical degenerative pathology such as medial temporal lobe atrophy. We set out to investigate the relation between blood pressure and medial temporal lobe atrophy in patients with senile and presenile Alzheimer's disease with or without white matter lesions. METHODS: We determined the relation between blood pressure and pulse pressure and medial temporal lobe atrophy on MRI in 159 patients with Alzheimer's disease, stratified on white matter lesions and age at onset of dementia. RESULTS: There was a linear relation between systolic blood pressure and pulse pressure (both in tertiles) and the severity of medial temporal lobe atrophy (p(trend) = 0.05 and p(trend) 0.03, respectively). A significant relation was found between pulse pressure [beta = 0.08 (95% CI: 0.00-0.15; p = 0.05) per 10 mm Hg] and (borderline significant) systolic blood pressure [beta = 0.05 (95% CI: -0.01 to 0.11; p = 0.1) per 10 mm Hg] and medial temporal lobe atrophy. White matter lesions and age-stratified analysis revealed a significant association between systolic blood pressure and pulse pressure and medial temporal lobe atrophy, only in the subsample with white matter lesions and in the subsample with a senile onset of dementia. The relations were independent of severity of dementia and diabetes mellitus. CONCLUSIONS: Systolic blood pressure and pulse pressure are associated with medial temporal lobe atrophy in Alzheimer's disease, especially in the presence of white matter lesions and in patients with a late onset of dementia. Our finding may be another step in providing a rationale on how vascular factors could ultimately result in Alzheimer's disease.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/*pathology/physiopathology;Atrophy/pathology;*Blood Pressure;Brain/*pathology;Diabetes Complications;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Temporal Lobe/*pathology","Korf, E. S.;Scheltens, P.;Barkhof, F.;de Leeuw, F. E.",2005,,10.1159/000088464,0,
3216,Acute confusional states in the elderly: A radiological evaluation,"Computed tomography of the head was carried out on 35 patients who received a hospital diagnosis of delirium according to the DSM-III, and 25 controls without cognitive disturbance. There were no statistically significant differences in the mean age of the groups of in the cortical atrophy score as measured by the mean width of the four largest sulci in the three uppermost tomographic cuts. Instead, the delirious patients differed from the controls in the frontal horn and cella media indices, in the width of the third ventricle and Sylvian fissure at insula on the left side. There was also a significant excess of low attenuation, brain infarct-type areas in the delirious patients. The study confirms the marked predisposing role of the structural brain diseases (primary degenerative and multi-infarct type dementias, Parkinsonism) in the development of acute delirium in elderly patients.",age;aged;brain atrophy;brain infarction;clinical article;computer analysis;computer assisted tomography;delirium;human,"Koponen, H.;Hurri, L.;Stenback, U.;Riekkinen, P. J.",1987,,,0,
3217,Computed tomography findings in delirium,"Computerized tomography of the head was carried out on 69 elderly patients who met the DSM-III criteria for delirium and 31 neurological controls in order to evaluate the focal changes and generalized brain atrophy associated with delirium. Neither the difference between the mean ages nor the sex distribution in these groups was statistically significant. The delirious patients differed from the controls significantly in ventricular dilatation and cortical atrophy, and there was a statistically significant correlation between the width of the sylvian fissure and Mini-Mental State Examination score. Focal changes were also statistically more common in the delirious patients, and these changes tended to concentrate in the high-order association areas of the right hemisphere. Results suggest a marked predisposing role for the structural brain diseases (primary degenerative and multi-infarct type dementias, parkinsonism) in the development of delirium in elderly patients.","Aged;Aged, 80 and over;Brain/radiography;Delirium/physiopathology/psychology/*radiography;Electroencephalography;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Prospective Studies;Reference Values;*Tomography, X-Ray Computed","Koponen, H.;Hurri, L.;Stenback, U.;Mattila, E.;Soininen, H.;Riekkinen, P. J.",1989,Apr,,0,
3218,Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study,"PURPOSE: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS. MATERIAL AND METHODS: Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains. RESULTS: ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (rho = - 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05). CONCLUSIONS: The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.","AC, anterior commissure;ALS, amyotrophic lateral sclerosis;ALS-EX, ALS with executive impairment;ALS-NECI, ALS with non-executive cognitive impairment;ALSFRS-R, revised ALS functional rating scale;ATL, anterior temporal lobe;Amyotrophic lateral sclerosis;CC, corpus callosum;CST, corticospinal tract;Corpus callosum;DD, disease duration;DPR, disease progression rate;DTI, diffusion tensor imaging;Diffusion tensor imaging;FA, fractional anisotropy;FTD, frontotemporal dementia;HC, healthy control;Hb, hemoglobin;Interhemispheric connectivity;NIRS, near-infrared spectroscopy;Near-infrared spectroscopy;TBSS, tract based spatial statistics;WM, white matter;fMRI, functional magnetic resonance imaging;pALS, pure ALS no cognitive impairment;rs-FC, resting-state functional connectivity;rs-fNIRS, resting-state functional NIRS","Kopitzki, K.;Oldag, A.;Sweeney-Reed, C. M.;Machts, J.;Veit, M.;Kaufmann, J.;Hinrichs, H.;Heinze, H. J.;Kollewe, K.;Petri, S.;Mohammadi, B.;Dengler, R.;Kupsch, A. R.;Vielhaber, S.",2016,,,0,
3219,"Physical activity, structural brain changes and cognitive decline. The SMART-MR study","Objective: We aimed to examine the cross-sectional and prospective relationship between leisure time physical activity, brain MRI abnormalities and cognitive performance in patients with vascular disease. Methods: Within the SMART-MR study, 1.5T MRI of the brain and neuropsychological examinations were performed at baseline (n=1232) and after 3.9±0.4 years follow-up (n=663). Automatic brain segmentation was used to quantify intracranial (ICV), total brain, ventricular, and white matter lesion (WML) volumes. Brain infarcts were rated visually. Level of physical activity was expressed in metabolic equivalents (MET) hours p/week. With linear regression analysis we examined associations of level of physical activity with brain MRI measures and with cognitive performance, adjusted for potential confounders. For the association with brain infarcts relative risks (RR) were calculated with Poisson regression. Results: At baseline, an increase in physical activity of one SD (39.7 METh/w) was significantly associated with larger total brain volume (B=0.20% of ICV; 95% CI 0.06; 0.33%). A trend was found for the association of physical activity with smaller ventricular volume (B=-0.04% of ICV; 95% CI-0.09; 0.02%) and with a decreased risk for brain infarcts (RR=0.91, 95% CI: 0.82-1.02). No association was found with smaller WML volume (B=-0.02% of ICV; 95% CI-0.07; 0.04%). No associations with change in brain structures over time were observed. Also, no associations between physical activity and cognitive performance or cognitive decline were found. Conclusion: These data suggest that leisure time physical activity does not have a significant contribution in preventing or slowing down brain abnormalities and cognitive decline in this cohort of middle-aged individuals already burdened with vascular disease. © 2014 Elsevier Ireland Ltd.",adult;anatomical concepts;article;automatic brain segmentation;brain atrophy;brain damage;brain infarction;brain region;brain size;brain structure;cohort analysis;controlled study;cross-sectional study;disease association;disease course;executive function;female;follow up;functional assessment;high risk patient;human;intracranial volume;leisure;linear regression analysis;major clinical study;male;memory;mental deterioration;mental performance;metabolic equivalent;middle aged;nervous system parameters;neurologic examination;neuropsychological test;nuclear magnetic resonance;nuclear magnetic resonance scanner;physical activity;prevention;priority journal;prospective study;risk assessment;risk factor;structure analysis;total brain volume;vascular disease;ventricular volume;white matter lesion;white matter lesion volume;Gyroscan ACS-NT,"Kooistra, M.;Boss, H. M.;van der Graaf, Y.;Kappelle, L. J.;Biessels, G. J.;Geerlings, M. I.;Algra, A.;Doevendans, P. A.;van der Graaf, Y.;Grobbee, D. E.;Rutten, G. E. H. M.;Kappelle, L. J.;Mali, W. P. T. M.;Moll, F. L.;Visseren, F. L. J.",2014,,,0,
3220,A cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mimics on brain magnetic resonance imaging inmyotonic dystrophy type i,,myotonic dystrophy protein kinase;adult;brain atrophy;brain hemorrhage;CADASIL;case report;cataract;DMPK gene;female;genetic screening;human;image analysis;lacunar stroke;middle aged;mitochondrial myopathy;myotonic dystrophy;neuroimaging;note;nuclear magnetic resonance imaging;priority journal;ptosis;weakness;white matter lesion,"Konzen, D.;De Souza, C. F. M.;Saute, J. A. M.",2017,,10.1001/jamaneurol.2017.0399,0,
3221,Multivariate statistical analysis of diffusion imaging parameters using partial least squares: Application to white matter variations in Alzheimer's disease,"Diffusion magnetic resonance imaging (dMRI) is a unique technology that allows the noninvasive quantification of microstructural tissue properties of the human brain in healthy subjects as well as the probing of disease-induced variations. Population studies of dMRI data have been essential in identifying pathological structural changes in various conditions, such as Alzheimer's and Huntington's diseases (Salat et al., 2010; Rosas et al., 2006). The most common form of dMRI involves fitting a tensor to the underlying imaging data (known as diffusion tensor imaging, or DTI), then deriving parametric maps, each quantifying a different aspect of the underlying microstructure, e.g. fractional anisotropy and mean diffusivity. To date, the statistical methods utilized in most DTI population studies either analyzed only one such map or analyzed several of them, each in isolation. However, it is most likely that variations in the microstructure due to pathology or normal variability would affect several parameters simultaneously, with differing variations modulating the various parameters to differing degrees. Therefore, joint analysis of the available diffusion maps can be more powerful in characterizing histopathology and distinguishing between conditions than the widely used univariate analysis. In this article, we propose a multivariate approach for statistical analysis of diffusion parameters that uses partial least squares correlation (PLSC) analysis and permutation testing as building blocks in a voxel-wise fashion. Stemming from the common formulation, we present three different multivariate procedures for group analysis, regressing-out nuisance parameters and comparing effects of different conditions. We used the proposed procedures to study the effects of non-demented aging, Alzheimer's disease and mild cognitive impairment on the white matter. Here, we present results demonstrating that the proposed PLSC-based approach can differentiate between effects of different conditions in the same region as well as uncover spatial variations of effects across the white matter. The proposed procedures were able to answer questions on structural variations such as: ""are there regions in the white matter where Alzheimer's disease has a different effect than aging or similar effect as aging?"" and ""are there regions in the white matter that are affected by both mild cognitive impairment and Alzheimer's disease but with differing multivariate effects?""",Aged;Alzheimer Disease/ diagnostic imaging/ pathology;Brain/diagnostic imaging/ pathology;Cognitive Dysfunction/diagnostic imaging/pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Least-Squares Analysis;Male;Multivariate Analysis;White Matter/diagnostic imaging/ pathology;Alzheimer's disease;Diffusion tensor imaging;Partial least squares,"Konukoglu, E.;Coutu, J. P.;Salat, D. H.;Fischl, B.;Alzheimer's Disease Neuroimaging, Initiative",2016,Jul 1,,0,
3222,Multivariate statistical analysis of diffusion imaging parameters using partial least squares: Application to white matter variations in Alzheimer's disease,"Diffusion magnetic resonance imaging (dMRI) is a unique technology that allows the noninvasive quantification of microstructural tissue properties of the human brain in healthy subjects as well as the probing of disease-induced variations. Population studies of dMRI data have been essential in identifying pathological structural changes in various conditions, such as Alzheimer's and Huntington's diseases (Salat et al., 2010; Rosas et al., 2006). The most common form of dMRI involves fitting a tensor to the underlying imaging data (known as diffusion tensor imaging, or DTI), then deriving parametric maps, each quantifying a different aspect of the underlying microstructure, e.g. fractional anisotropy and mean diffusivity. To date, the statistical methods utilized in most DTI population studies either analyzed only one such map or analyzed several of them, each in isolation. However, it is most likely that variations in the microstructure due to pathology or normal variability would affect several parameters simultaneously, with differing variations modulating the various parameters to differing degrees. Therefore, joint analysis of the available diffusion maps can be more powerful in characterizing histopathology and distinguishing between conditions than the widely used univariate analysis. In this article, we propose a multivariate approach for statistical analysis of diffusion parameters that uses partial least squares correlation (PLSC) analysis and permutation testing as building blocks in a voxel-wise fashion. Stemming from the common formulation, we present three different multivariate procedures for group analysis, regressing-out nuisance parameters and comparing effects of different conditions. We used the proposed procedures to study the effects of non-demented aging, Alzheimer's disease and mild cognitive impairment on the white matter. Here, we present results demonstrating that the proposed PLSC-based approach can differentiate between effects of different conditions in the same region as well as uncover spatial variations of effects across the white matter. The proposed procedures were able to answer questions on structural variations such as: ""are there regions in the white matter where Alzheimer's disease has a different effect than aging or similar effect as aging?"" and ""are there regions in the white matter that are affected by both mild cognitive impairment and Alzheimer's disease but with differing multivariate effects?""",,"Konukoglu, E.;Coutu, J. P.;Salat, D. H.;Fischl, B.",2016,Apr 18,10.1016/j.neuroimage.2016.04.038,0,
3223,Dementia and bipolar disorder on the borderline of old age,"Dementia and bipolar disorder have been traditionally considered two separate clinical entities. However, recent preclinical and clinical data in elderly people suggest that they are in fact related. Several theories have been put forward to interpret their relationship which could be summed up as follows: (1) Dementia could increase the risk for the emergence of bipolar symptoms, or (2) conversely, bipolar disorder might be associated with heightened risk for developing pseudodementia or dementia. (3) Alternatively, dementia, other brain diseases or drugs affecting brain function could lead to the combination of symptoms of dementia and bipolar disorder in elderly individuals. The two disorders demonstrate similarities with respect to their clinical expression (agitation, psychotic, mood and cognitive symptoms) and structural brain neuroimaging (enlarged lateral ventricles and white matter hyperintensities using magnetic resonance imaging-MRI). Despite the above similarities, the two disorders also have important differences. As expected, cognitive symptoms prevail in dementia and mood symptoms in bipolar disorder. In dementia but not in bipolar disorder there is evidence that brain structural abnormalities are diffuse and hippocampal volumes are smaller. Dementia and bipolar disorder present different abnormalities in functional brain neuroimaging. The pattern of ""ventral"" hyperactivity and ""dorsal"" hypoactivity in brain emotional circuits at rest is revealed in bipolar disorder but not dementia. With respect to their treatment, acetylcholinesterase inhibitors and memantine are indicated against cognitive symptoms in dementia and also improve behavioural and psychological symptoms appearing during the course of dementia. Lithium, anticonvulsants, antipsychotics and antidepressants are effective in the management of the acute episodes of bipolar disorder of younger adults, but there are not yet evidence-based data in elderly bipolar patients. It is likely that the efficacy of anticonvulsants and antipsychotics is superior during acute bipolar episodes in elderly individuals, although both drug categories have been associated with important adverse effects. Current data suggest that the best option during the maintenance phase of the elderly bipolar disorder is the continuation of agents which have been shown effective in the management of acute episodes. The appropriate treatment of cognitive symptoms in elderly bipolar patients has not been thoroughly investigated. In addition, the therapeutic value of psychotropics except cholinesterase inhibitors and memantine in dementia is still controversial, due to their association with side effects. Recent studies which have focused on the role of lithium in dementia could help clarify the relationship of dementia and elderly bipolar disorder. Although there are promising findings with respect to the value of lithium treatment in the prevention of dementia, the existing clinical studies do not support any beneficial effect of lithium administration on enhancing cognitive functioning of people with dementia. The specific role of lithium in dementia and the preventive value of interventions against vascular risk factors in both disorders remain to be evaluated in future prospective studies.",,"Kontis, D.;Theochari, I.;Tsalta, E.",2013,2013,,0,
3224,A 26-year-old woman of interval form of acute carbon monoxide intoxication with cerebrospinal fluid abnormalities,"A 26-year-old woman was admitted to our hospital for the treatment of hyperbaric oxygen therapy to acute carbon monoxide intoxication. The consciousness disturbance improved and she was discharged after 23 times of the hyperbaric oxygen therapy. However, she was readmitted because of dementia and urinary incontinence after 22 days. Diffusion-weighted images showed bright high signal intensities in the periventicular white matter and corpus callosum. The condition was considered to be an interval form of carbon monoxide intoxication. She was treated by 38 times of the hyperbaric oxygen therapy with cytochrome C and fully recovered. MRI images and cerebrospinal fluid abnormality (high protein content and IgG index) became normalized somewhat later than the improvement of the symptoms. By an investigation utilizing diffusion-weighted images, we thought that not only the demyelination which mentioned formerly, but the vasogenic edema was involving in the mechanism of these high signal intensities in the periventicular white matter of the interval form. And in the range which we searched, this is the first report which mentioned the abnormal findings of cerebrospinal fluid in an interval form of carbon monoxide intoxication. So we believe this case is very important for telling us suspected the mechanism and some indications about the treatment of an interval form.",,"Kono, Y.;Nakamori, T.;Imafuku, I.;Washizaki, K.;Kunimoto, M.",2005,July,,0,
3225,[The study of dementia patients who showed intellectual improvement after admission to a hospital where they could be given special therapy for dementia],"The authors evaluated the changes in the scores on Hasegawa's rating scale for dementia (HRSD) of demented patients in a hospital for dementia. The subjects in this study were 69 patients (12 males and 57 females) including 34 with dementia of the Alzheimer type (DAT), 30 with multi-infarct dementia (MID) and 5 with mixed dementia. Their average age was 75.6 years and the mean period after symptom onset was 2.5 years. The observation period was 5 months after admission to the hospital. We rated HRSD on admission and each month after admission. During the observation period, 65 patients received drugs orally and 65 patients were given rehabilitation for impaired cerebral function. We tried to classify the pattern of change in the HRSD into 5 groups as follows; 1) no remarkable change or deterioration, 2) wavering, 3) improvement during only the first month, 4) improvement from the first month after admission, 5) improvement from admission. We assumed that the patients in group 3) had been underestimated on admission. Their mental states might have been confused on admission because of the change in their living environment. Thus we rejected this group for statistical analysis and compared the medical characteristics of those in the non-improved group (1 and 2) with those in the improved group (4 and 5). The period from onset of symptoms in the improved group was shorter than in the non-improved group (p less than 0.05). Moreover there was a tendency (p less than 0.1) toward less abnormal findings in the EEG and less cerebral atrophy on CT scan in the improved group.(ABSTRACT TRUNCATED AT 250 WORDS)","Aged;Aged, 80 and over;Dementia/*psychology/therapy;Female;Hospitalization;Hospitals, Psychiatric;Humans;*Intelligence;Male;Middle Aged","Kono, K.;Endo, H.;Yamamoto, T.;Kuzuya, F.",1989,Nov,,0,
3226,Do white matter changes have clinical significance in Alzheimer's disease?,"BACKGROUND: Although white matter changes visible with MRI are generally considered to result from ischemia, it has become clear that these changes also appear in patients with Alzheimer's disease (AD). However, their significance in AD is unknown. OBJECTIVE: We evaluated the clinical significance of white matter changes in AD. METHODS: Ninety-six AD patients (79.4 +/- 5.92 years old) and 48 age-matched control subjects (80.0 +/- 7.03 years old) participated in the study. Three neuroradiologists assessed the degree of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using a modified Fazekas' rating scale. We examined whether there was a difference in the severity and the histogram pattern of the white matter changes, or in vascular factors (hypertension, diabetes mellitus, and ischemic heart disease) between the two groups. We also analyzed the association between the severity of the white matter changes and the degree of dementia (MMSE score and disease duration). RESULTS: There were no differences in the vascular factors between AD and control subjects. The degree of PVH in AD was severe compared with that in the control subjects. In histograms of the number of subjects with each degree of PVH severity, the distribution of AD patients had peaks at both the low and intermediate degrees of PVH, while most of the controls had a low degree of PVH. There was no difference in the degree or the histogram pattern of DWMH between the two groups. The severity of white matter changes was not associated with severity of dementia in AD. CONCLUSIONS: Although PVH might have several causative factors, and may have some clinical significance, the change itself does not contribute to the progression of AD.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Brain/*pathology;Case-Control Studies;Humans;Magnetic Resonance Imaging;Statistics, Nonparametric","Kono, I.;Mori, S.;Nakajima, K.;Nakagawa, M.;Watanabe, Y.;Kizu, O.;Yamada, K.;Sakai, Y.",2004,Jul-Aug,10.1159/000078353,0,
3227,A case of CADASIL without characteristic anterior temporal pole lesion diagnosed by skin biopsy,"A 40 year-old man with migraine presented cerebral ischemic attacks several times in one year. He had no risk factors for cerebrovascular disease including hypertension, but had strong family history suggesting autosomal dominant inheritance. A brain MRI on T(2) weighted and FLAIR images revealed patchy and confluent hyper intensity areas in the subcortical white matters and bilateral external capsules, while no anterior temporal pole lesions characteristic of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were detected. His skin biopsy demonstrated granular osmiophilic materials (GOM) on the basement membrane of the vascular smooth muscle cells in dermis as shown by an electron microscope. The following mutational analysis of the Notch3 gene disclosed a missense mutation of p.Arg133Cys in exon 3. Molecular diagnosis of CADASIL may be time consuming because Notch3 is a huge gene and mutations may occur at multiple sites. GOM on skin biopsy is diagnostic especially in cases where anterior temporal pole involvement on MRI is negative.",,"Konno, T.;Umeda, M.;Umeda, Y.;Nozaki, H.;Oyake, M.;Fujita, N.",2011,October,,0,
3228,"Optimization and Biodistribution of [(11)C]-TKF, An Analog of Tau Protein Imaging Agent [(18)F]-THK523","The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [(18)F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [(11)C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [(11)C]-TKF can be made by reaction precursor with [(11)C]MeOTf or (11)CH(3)I, but [(11)C]MeOTf will give us higher labeling yields and specific activity. [(11)C]-TKF presented better brain uptake in normal mouse than [(18)F]-THK523 (3.23% +/- 1.25% ID.g(-1) vs. 2.62% +/- 0.39% ID.g(-1) at 2 min post-injection). The acute toxicity studies of [(11)C]-TKF were unremarkable.",Alzheimer's disease;imaging;neurofibrillary tangles (NFTs);positron emission tomography (PET);tau,"Kong, Y.;Guan, Y.;Hua, F.;Zhang, Z.;Lu, X.;Zhu, T.;Zhao, B.;Zhu, J.;Li, C.;Chen, J.",2016,,10.3390/molecules21081019,0,
3229,Early involvement of the corpus callosum in a patient with hereditary diffuse leukoencephalopathy with spheroids carrying the de novo K793T mutation of CSF1R,"We herein report the case of a 41-year-old Japanese man with hereditary diffuse leukoencephalopathy with spheroids (HDLS) who carried the de novo K793T mutation in the colony-stimulating factor 1 receptor gene (CSF1R). He showed a gradual decline of his cognitive and mental functions over the following six months. On brain MRI, a thin corpus callosum with T2-and FLAIR-high signal intensity in the splenium was con-spicuous, whereas cerebral deep and periventricular white matter lesions were mild. We propose that a diag-nosis of HDLS should be considered in patients with presenile dementia presenting with corpus callosum le-sions on MRI, even in cases with a lack of any apparent family history. © 2013 The Japanese Society of Internal Medicine.",colony stimulating factor receptor;genomic DNA;protein;tau protein;adult;article;brain angiography;case report;cerebrospinal fluid examination;colony stimulating factor 1 receptor gene;corpus callosum;dysarthria;flexor reflex;gene mutation;hemiplegia;hereditary diffuse leukoencephalopathy with spheroid;human;leukoencephalopathy;male;Mini Mental State Examination;neurologic examination;nuclear magnetic resonance imaging;polymerase chain reaction;receptor gene;speech disorder;tendon reflex;unsteadiness,"Kondo, Y.;Kinoshita, M.;Fukushima, K.;Yoshida, K.;Ikeda, S.",2013,,,0,
3230,An autopsied case of corticobasal degeneration showing severe cerebral atrophy over a protracted disease course of 16 years,"The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated left-dominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs.",tau protein;aged;agraphia;article;autopsy;basal ganglion;brain atrophy;brain cortex;brain stem;case report;cell loss;clinical feature;coiled body;computer assisted tomography;corticobasal degeneration;daily life activity;disease course;dysphagia;female;frontal lobe;gait disorder;gliosis;globus pallidus;human;human tissue;immunoblotting;immunohistochemistry;neurochemistry;neuroimaging;neuropathology;priority journal;senile plaque;severe cerebral atrophy;stereotypy;substantia nigra;temporal lobe;white matter,"Kondo, D.;Hino, H.;Shibuya, K.;Fujisawa, K.;Kosaka, K.;Hirayasu, Y.;Yamamoto, R.;Kasanuki, K.;Minegishi, M.;Sato, K.;Hosokawa, M.;Arai, T.;Arai, H.;Iseki, E.",2015,,,0,
3231,Right parietal lobe syndrome as a clinical variant of Creutzfeldt-Jakob disease,"We report a 57-year-old patient with Creutzfeldt-Jakob disease that initially presented with right parietal lobe syndrome. He featured early dystonic and hemiparetic posture of the left upper limb, finger agnosia, geographic disorientation and acalculia and developed myoclonus from the left upper extremity and right-sided periodic synchronized discharges. He died 2 years and 3 months later. Brain autopsy revealed a marked reduction in brain weight, extensive cortical spongiform changes and white matter degeneration. Immunolabeled prion proteins were deposited diffusely in the neuropil. Accentuation of the cortical change was unclear but white matter degeneration was more severe in the right parietal lobe than in the left parietal lobe. Right parietal lobe syndrome is rarely reported as an initial symptom of Creutzfeldt-Jakob disease and can be a clinical variant of the disease. © 2006 Japanese Psychogeriatric Society.",prion protein;adult;agnosia;article;autopsy;brain atrophy;brain disease;case report;cause of death;clinical feature;codon usage;Creutzfeldt Jakob disease;demyelination;disease severity;disorientation;dystonia;electroencephalogram;hemiparesis;histopathology;homozygosity;human;human tissue;immunohistochemistry;male;Mini Mental State Examination;myoclonus;nuclear magnetic resonance imaging;nuclear magnetic resonance spectroscopy;parietal lobe;pneumonia;priority journal;protein analysis;right parietal lobe syndrome;single photon emission computer tomography,"Komuro, R.;Kobayashi, K.;Shimazaki, M.;Sugimori, K.;Koshino, Y.;Satou, K.;Oda, Y.",2006,,,0,
3232,Assessment of demented patients by dynamic SPECT of inhaled xenon-133,"We studied the potential for using dynamic single photon emission computed tomography of inhaled xenon-133 (133Xe) gas in the assessment of demented patients. An advanced ring-type single photon emission computed tomography (SPECT) ""HEADTOME"" with improved spatial resolution [15 mm in full width at half maximum (FWHM)] was used for tomographic measurement of regional cerebral blood flow (rCBF). All 34 patients underwent a detailed psychiatric examination and x-ray computed tomography scan, and matched research criteria for Alzheimer's disease (n = 13), senile dementia of the Alzheimer type (n = 9), or multi-infarct dementia (n = 12). In comparison with a senile control group (n = 7), mean CBF of both the whole brain and the temporo-parietal region was significantly less in the Alzheimer's disease and senile dementia Alzheimer type groups, but no significant difference was seen between the senile control group and multi-infarct dementia group. The correlation was 0.72 (p less than 0.004) between the mean CBF of the whole brain and the score of Hasegawa's Dementia Scale, and 0.94 (p less than 0.0001) between rCBF of the temporo-parietal region and the scale in Alzheimer's disease. In the senile dementia Alzheimer type group, the correlations were 0.77 (p less than 0.01) and 0.83 (p less than 0.004) respectively. No significant correlations were found in the multi-infarct dementia group. A temporo-parietal reduction in the distribution of the rCBF characteristic in the Alzheimer's disease group and a patchy whole brain reduction characteristic in the multi-infarct dementia group was detected. The ability of our improved SPECT to provide both quantitative measurement of rCBF and characteristic rCBF distribution patterns, makes it a promising tool for research or routine examination of demented patients.","Adult;Aged;Alzheimer Disease/*radionuclide imaging;Brain/*radionuclide imaging;Cerebrovascular Circulation;Dementia/*radionuclide imaging;Dementia, Multi-Infarct/*radionuclide imaging;Humans;Middle Aged;*Tomography, Emission-Computed;*Xenon Radioisotopes","Komatani, A.;Yamaguchi, K.;Sugai, Y.;Takanashi, T.;Kera, M.;Shinohara, M.;Kawakatsu, S.",1988,Oct,,0,
3233,Impact of night-time blood pressure on cerebral white matter hyperintensity in elderly hypertensive patients,"AIM: Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke. We investigated the relationship between ambulatory blood pressure monitoring levels and quantitatively measured WMH volumes among elderly hypertensive patients with well-controlled blood pressure (BP) to re-evaluated effective hypertension management methods to prevent the progression of WMH. METHODS: Participants comprised 84 hypertensive patients aged between 65 and 75 years without symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke or cognitive dysfunction. RESULTS: Linear regression analysis showed that office BP was not associated with WMH volume increases. Raised night-time systolic BP (P = 0.013) were associated with greater WMH volumes during ambulatory blood pressure monitoring. To clarify the effect of asleep systolic BP on WML volume, we then classified patients into two systolic BP groups as follows: <125 mmHg (n = 47) and >/=125 mmHg (n = 37). Baseline characteristics were almost similar in both groups, except the dipper type of circadian BP variation was significantly common in the group with night-time systolic BP <125 mmHg. However, WMH volume was greater in the group with night-time systolic BP >/=125 mmHg than that in the <125 mmHg group (9.0 +/- 8.4 mL vs 4.1 +/- 4.3 mL, P = 0.015). CONCLUSION: Higher night-time systolic BP levels were observed to contribute greater WMH volumes in elderly hypertensive patients. To prevent the progression of WMH, controlling BP on the basis of ambulatory blood pressure monitoring is important.","Aged;Aging/*physiology;Antihypertensive Agents/therapeutic use;Blood Pressure/physiology;Blood Pressure Determination/*methods;Blood Pressure Monitoring, Ambulatory;*Circadian Rhythm;Cohort Studies;Diffusion Magnetic Resonance Imaging/methods;Disease Progression;Female;Humans;Hypertension/complications/*diagnosis/drug therapy;Japan;Leukoaraiosis/etiology/pathology;Linear Models;Male;Prognosis;Prospective Studies;Risk Assessment;White Matter/*pathology;ambulatory blood pressure monitoring;cerebral white matter hyperintensity;circadian blood pressure variation;night-time blood pressure;office blood pressure","Kokubo, M.;Shimizu, A.;Mitsui, T.;Miyagi, M.;Nomoto, K.;Murohara, T.;Toba, K.;Sakurai, T.",2015,Dec,10.1111/ggi.12662,0,
3234,"Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus","Background: It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). Method: In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy. Results: The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer’s disease (AD)-related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans’ index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001). Conclusions: The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.",amyloid beta protein;tau protein;aged;Alzheimer disease;article;B wave;brain atrophy;brain biopsy;brain ventricle peritoneum shunt;brain ventricle pressure;female;human;human tissue;intracranial pressure;intracranial pressure monitoring;major clinical study;male;medial temporal lobe;neuroimaging;normotensive hydrocephalus;nuclear magnetic resonance imaging;priority journal;protein phosphorylation;pulse wave;radiodiagnosis;retrospective study;subarachnoid space;suprasylvian gyrus;treatment outcome;white matter;x-ray computed tomography,"Kojoukhova, M.;Vanha, K. I.;Timonen, M.;Koivisto, A. M.;Nerg, O.;Rummukainen, J.;Rauramaa, T.;Vanninen, R.;Jääskeläinen, J. E.;Sutela, A.;Leinonen, V.",2017,,10.1007/s00701-016-3025-8,0,
3235,Expression of human apolipoprotein E downregulates amyloid precursor protein-induced ischemic susceptibility,"BACKGROUND AND PURPOSE: Epidemiological findings and experimental data on transgenic mice show that Alzheimer's disease-related changes render the brain more susceptible to ischemic damage. We studied whether the previously observed vulnerability in mice overexpressing the 751-amino-acid isoform of human amyloid precursor protein (APP751) is regulated by human apolipoprotein E (apoE) alleles, which determine the relative risk for Alzheimer's disease and the susceptibility to various forms of acute brain damage. METHODS: Aged apoE knock out (KO) mice, mice overexpressing APP751 in the apoE KO background and mice expressing either human apoE3 or apoE4 and APP751 in the apoE KO background were exposed to permanent occlusion of the middle cerebral artery (MCA). Infarct volumes were quantified from T2-weighted magnetic resonance images 24 hours after the MCA occlusion. Local cortical blood flow was monitored by laser Doppler flowmetry. Ischemia-induced microgliosis was detected by immunohistochemistry. RESULTS: Overexpression of human APP751 significantly increased the infarct volumes in apoE KO mice. Furthermore, this APP751-induced ischemic vulnerability was attenuated by the coexpression of either human apoE isoform. MCA occlusion resulted in a similar relative reduction in cortical blood flow in all mouse groups. Vascular anatomy showed no variation in the MCA territory between the groups. Instead, the expression of human apoE isoforms reduced the ischemia-induced microgliosis. CONCLUSIONS: Expression of either the human apoE3 or apoE4 isoform protects against the increased ischemic vulnerability observed in aged mice overexpressing human APP751, probably by modulating the inflammatory response induced by MCA occlusion.","Aging/metabolism;Amyloid beta-Protein Precursor/biosynthesis/genetics/ pharmacology;Animals;Apolipoprotein E3;Apolipoprotein E4;Apolipoproteins E/ biosynthesis/deficiency/genetics;Blood Flow Velocity;Brain Ischemia/etiology/ genetics/pathology;Cerebral Cortex/blood supply/metabolism/pathology;Cerebrovascular Circulation/genetics;Disease Models, Animal;Down-Regulation/ physiology;Genetic Predisposition to Disease;Gliosis/pathology;Humans;Immunohistochemistry;Infarction, Middle Cerebral Artery/complications/pathology;Laser-Doppler Flowmetry;Magnetic Resonance Imaging;Mice;Mice, Inbred C57BL;Mice, Knockout;Mice, Transgenic;Microglia/pathology;Protein Isoforms/biosynthesis/genetics/pharmacology","Koistinaho, M.;Kettunen, M. I.;Holtzman, D. M.;Kauppinen, R. A.;Higgins, L. S.;Koistinaho, J.",2002,Jul,,0,
3236,Neuroimaging in the diagnosis of dementia,"Dementia is a common disease, affecting 14% of the over 65s with numbers steadily increasing. The recent development of brain imaging techniques have contributed to the better diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB),vascular dementia (VaD),frontotemporal lobar degeneration (FTLD) and corti-cobasal degeneration (CBD).Structural imaging, previously used to exclude non-degenerative causes for dementia, is becoming increasingly important in the diagnostic procedure. Atrophy of the hippocampus and entorhinal cortex suggests the presence of AD, and cortical and subcortical infarcts and white matter lesions are characteristic of VaD. Disease-specific patterns of regional hypoperfusion on single-photon emission computed tomography (SPECT) or hypometabolism on positron emission tomography (PET) could further help differentiate degenerative dementia. Newer techniques show great promise to detect the pathological basis of dementia, such as amyloid in AD. This review describes the use of these imaging techniques in dementia. Together, these imaging techniques will be useful tools for early diagnosis, disease monitoring, and consequently contribute to developing effective treatments for dementia.",,"Koide, Y.;Hayashi, T.;Iwata, A.",2013,25,,0,
3237,Three-year changes in leisure activities are associated with concurrent changes in white matter microstructure and perceptual speed in individuals aged 80 years and older,"Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we investigated the role of change in white matter microstructure in the activities-cognition link. We used repeated assessments of engagement, perceptual speed, and white matter microstructure (probed with diffusion tensor imaging) in a population-based sample of individuals over 80 years without dementia (n = 442, Mage = 85.1; n = 70 for diffusion tensor imaging; 2 occasions 3 years apart). Using multivariate latent change modeling, we observed positive correlations among changes in predominantly social activities, white matter microstructure, and perceptual speed. Interindividual differences in change in white matter microstructure statistically accounted for the association between change in leisure activities and change in perceptual speed. However, as analyses are based on observational data from 2 measurement occasions, causality remains unclear.",,"Kohncke, Y.;Laukka, E. J.;Brehmer, Y.;Kalpouzos, G.;Li, T. Q.;Fratiglioni, L.;Backman, L.;Lovden, M.",2016,May,10.1016/j.neurobiolaging.2016.02.013,0,
3238,Periventricular attenuation of the density of cerebral hemisphere white matter in computerized tomography of neuropsychiatric patients in the 2d half of life. Diagnostic significance and pathogenesis,"The images of cranial computed tomographies on 7.921 patients aging between 50 and 98 years were analyzed retrospectively concerning the occurrence of WMLA. 3.344 patients were suffering from psychogeriatric disorders (organic brain syndrome, dementia, depressive or delusional psychoses). Neurological diagnoses (stroke, TIA, Parkinson's disease, Huntington's disease, space occupying lesions, seizures, cerebral trauma, vertigo, chronic headache) occurred in 4.577 patients. WMLA was established in 761 cases. The combination of WMLA with cerebral atrophies, with single or multiple infarcts and with both infarcts and atrophy will be demonstrated within 4 groups: 1. organic brain syndrome and dementia, 2. depression and delusional states, 3. stroke and TIA, 4. other neurological diagnoses. In group one the combination of WMLA with atrophy and infarcts is the most common finding in CT. In group two WMLA without atrophies and infarcts are the main tissue changes in CT. Group three is marked mainly by the occurrence of recent infarcts together with WMLA. In group four again WMLA only, in some cases together with multiple infarcts, do occur mainly. Compared to the cases without WMLA in each group WMLA is seen in cases with organic brain syndromes and dementias three to five times more than in the other diagnostic groups. WMLA in computed tomography seems to be a common finding in patients and healthy individuals of old age. Therefore the diagnostic and differential diagnostic significance for brain diseases in old age is limited. Nevertheless in the field of psychogeriatric disorders it may be possess a certain value to understand the nature of such diseases. This value will be discussed and demonstrated considering the pathogenesis of WMLA on the basis of neuropathological results.",aged;article;atrophy;brain cortex;brain hemorrhage;brain ventricle;cognitive defect;computer assisted tomography;female;human;male;multiinfarct dementia;pathology;radiography,"Kohlmeyer, K.",1988,,,0,
3239,White matter low attenuation (WMLA) in computed tomography of patients with neuropsychiatric diseases in the presenile and senile period of life. Diagnostic significance and pathogenesis,"The images of cranial computed tomographies on 7,921 patients aging between 50 and 98 years were analyzed retrospectively concerning the occurrence of WMLA. 3,344 patients were suffering from psychogeriatric disorders (organic brain syndrome, dementia, depressive or delusional psychoses). Neurological diagnoses (stroke, TIA, Parkinson's disease, Huntington's disease, space occupying lesions, seizures, cerebral trauma, vertigo, chronic headache) occurred in 4,577 patients. WMLA was established in 761 cases. The combination of WMLA with cerebral atrophies, with single or multiple infarct and with both infarcts and atrophy will be demonstrated within 4 groups: 1. organic brain syndrome and dementia, 2. depression and delusional states, 3. stroke and TIA, 4. other neurological diagnoses. In group one the combination of WMLA with atrophy and infarcts is the most common finding in CT. In group two WMLA without atrophies and infarcts are the main tissue changes in CT. Group three is marked mainly by the occurrence of recent infarcts together with WMLA. In group four again WMLA only, in some cases together with multiple infarcts, do occur mainly. Compared to the cases without WMLA in each group WMLA is seen in cases with organic brain syndromes and dementias three to five times more than in the other diagnostic groups. WMLA in computed tomography seems to be a common finding in patients and healthy individuals of old age. Therefore the diagnostic and differential diagnostic significance for brain diseases in old age is limited. Nevertheless in the field of psychogeriatric disorders it may possess a certain value to understand the nature of such diseases. This value will be discussed and demonstrated considering the pathogenesis of WMLA on the basis of neuropathological results.",,"Kohlmeyer, K.",1988,1988,,0,
3240,Computer tomographical studies of dementia: The differential diagnosis of cerebrovascular and primarily degenerative brain atrophy,"It seems to be very complicated even for the experienced neurologist and psychiatrist to correlate the clinical syndrome of dementia to different causing cerebral processes such as a primarily degenerative brain atrophy, a chronic cerebrovascular insufficiency, or other rarer occurring brain diseases unless neurological signs and symptoms do indicate a focal brain lesion. Since computed tomography is able to show both focal and general changes of the brain tissue each patient presenting with a dementia clinically should have undergone such a neuroradiological investigation at least once, and if being negative even repeatedly. Computed tomography is able not only to detect unexpected treatable brain lesions as a cause of dementia for instance tumors, subdural hematomas, and communicating hydrocephalus to expect in about 6% of cases with the clinical diagnosis of dementia, but also it is able to help to make the differential diagnosis of the dementia of Alzheimer's and the multi-infarct-type in a high percentage. Nevertheless despite the use of computed tomography the pathogenesis of dementia even though being undoubtful clinically remains obscure in 15% of our material of 367 demented patients studied by computed tomography but presenting with a normal finding.",Alzheimer disease;brain atrophy;brain dysfunction;central nervous system;cerebrovascular disease;computer analysis;computer assisted tomography;dementia;diagnosis;human;organic brain syndrome,"Kohlmeyer, K.",1983,,,0,
3241,[Computer tomography contribution to the differential diagnosis of dementia of vascular origin (multi-infarction type) and primary degenerative dementia (Alzheimer type)] Computertomographischer Beitrag zur Differentialdiagnose vaskular bedingte Demenz (Multiinfarkt-Typ) und primar degenerative Demenz (Alzheimer-Typ),"Studies of computed tomography were performed in 367 patients diagnosed as dementia clinically. The mean age was 70.1 years. By the clinicians 240 were classified as senile dementia of Alzheimer's type, 79 as multiinfarct dementia, and 48 were not determined definitely. In 3%, the CT studies did detect treatable causes like tumors, subdural hematomas and communicating hydrocephalus. In about 57% was found by CT a diffuse brain atrophy without focal tissue changes as to expect if occurring a cerebrovascular disease. In 25% there were focal changes of the brain tissue in CT to define as residuals of infarctions in addition to the signs of cerebral atrophy. The results of the CT studies were normal in 15% despite of the evidence of dementia clinically. The analysis of the material did show that a cerebrovascular disease as a cause of dementia is suspected clinically in much more cases than CT studies are able to prove focal pathological changes of the brain tissue due to disorders of cerebral blood flow really.","Aged;Alzheimer Disease/ diagnostic imaging;Brain/ diagnostic imaging;Cerebral Infarction/complications;Dementia/ diagnosis/ diagnostic imaging/etiology;Diagnosis, Differential;Humans;Tomography, X-Ray Computed","Kohlmeyer, K.",1982,Nov-Dec,,0,
3242,Studies of computed tomography as a contribution for differential diagnosis between dementia due to cerebrovascular disease (multi-infarct type) and due to primarily degenerative cerebral atrophy (Alzheimer's type),,aged;Alzheimer disease;brain dysfunction;brain ischemia;central nervous system;cerebrovascular disease;computer analysis;computer assisted tomography;dementia;diagnosis;human;major clinical study;organic brain syndrome;peripheral vascular system;psychological aspect,"Kohlmeyer, K.",1982,,,0,
3243,Vascular-(multi-infarct-)dementia versus primarily degenerative (Alzheimer's) dementia: a study of rCBF and computed tomography (CT),,"Aged;Alzheimer Disease/*diagnosis;Atrophy;*Cerebrovascular Circulation;Dementia/*diagnosis;Diagnosis, Differential;Humans;Middle Aged;Tomography, X-Ray Computed;Xenon Radioisotopes","Kohlmeyer, K.",1982,,,0,
3244,[Computer tomography contribution to the differential diagnosis of dementia of vascular origin (multi-infarction type) and primary degenerative dementia (Alzheimer type)],"Studies of computed tomography were performed in 367 patients diagnosed as dementia clinically. The mean age was 70.1 years. By the clinicians 240 were classified as senile dementia of Alzheimer's type, 79 as multiinfarct dementia, and 48 were not determined definitely. In 3%, the CT studies did detect treatable causes like tumors, subdural hematomas and communicating hydrocephalus. In about 57% was found by CT a diffuse brain atrophy without focal tissue changes as to expect if occurring a cerebrovascular disease. In 25% there were focal changes of the brain tissue in CT to define as residuals of infarctions in addition to the signs of cerebral atrophy. The results of the CT studies were normal in 15% despite of the evidence of dementia clinically. The analysis of the material did show that a cerebrovascular disease as a cause of dementia is suspected clinically in much more cases than CT studies are able to prove focal pathological changes of the brain tissue due to disorders of cerebral blood flow really.","Aged;Alzheimer Disease/*radiography;Brain/*radiography;Cerebral Infarction/complications;Dementia/*diagnosis/etiology/*radiography;Diagnosis, Differential;Humans;Tomography, X-Ray Computed","Kohlmeyer, K.",1982,Nov-Dec,,0,
3245,"Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study","BACKGROUND: There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. METHODS: Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial-ankle pulse wave velocity was measured as an index of arterial stiffness. RESULTS: Both sarcopenic indices were modestly but significantly associated with brachial-ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. CONCLUSIONS: Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.","Aged;Aged, 80 and over;Ankle Brachial Index;Cognitive Dysfunction/complications/ epidemiology/pathology/physiopathology;Cross-Sectional Studies;Female;Frailty/epidemiology/physiopathology/psychology;Health Promotion;Humans;Japan/epidemiology;Male;Middle Aged;Muscular Atrophy/complications/epidemiology/physiopathology/psychology;Pulse Wave Analysis;Sarcopenia/complications/ epidemiology/physiopathology/psychology;Vascular Stiffness/ physiology;White Matter/ pathology;Cognitive impairment;Frailty;Sarcopenia;White matter hyperintensity","Kohara, K.;Okada, Y.;Ochi, M.;Ohara, M.;Nagai, T.;Tabara, Y.;Igase, M.",2017,Aug,,0,
3246,Quantitative MRI findings and cognitive impairment among community dwelling elderly subjects,"Objectives: To study the factors which influence cognitive impairment among elderly subjects living in a local community, based on both MRI and clinical findings, to further elucidate the causes of dementia, and also to help develop strategies for its prevention. Methods: Cranial MRI and other medical examinations were performed on non-demented elderly subjects who resided in one rural community. A total of 254 subjects aged from 60 to 91 years of age, with a mean age of 73.9 (SD 6.8) were examined. The mini mental state examination (MMSE) was used to identify cognitive impairment. White matter lesions and cerebral atrophy on MR images were measured quantitatively. A multivariate analysis was also performed with the existence of cognitive impairment as the dependent variable, and the MRI findings and clinical observations were used as the independent variables. Results: Cognitive impairment was present in 46 subjects (18.1%). They were older, had a lower educational level, and more frequent hypertension compared with those without cognitive impairment. The packed cell volume was lower in the impaired group. In addition, their MRI findings showed significantly larger quantities of white matter lesions and cerebral atrophy, as well as more infarcts. A logistic regression analysis demonstrated a significant relation among such factors as white matter lesions (odds ratio (OR) 1.575, 95% confidence interval (95% CI) 1.123-2.208), cerebral atrophy (OR 0.761, 95%CI 0.587-0.987), and lower education (OR 0.682, 95%CI 0.544-0.855) for subjects with a cognitive impairment. Conclusions: White matter lesions and cerebral atrophy are factors which induce a cognitive impairment in community dwelling elderly subjects without dementia. It is important to carefully watch for any abnormalities in these factors, and to perform cohort studies to check for the above risk factors, to both prevent and make an early diagnosis of dementia.",,"Koga, H.;Yuzuriha, T.;Yao, H.;Endo, K.;Hiejima, S.;Takashima, Y.;Sadanaga, F.;Matsumoto, T.;Uchino, A.;Ogomori, K.;Ichimiya, A.;Uchimura, H.;Tashiro, N.",2002,2002,,0,
3247,Cognitive Consequences of Multiple Lacunes and Leukoaraiosis as Vascular Cognitive Impairment in Community-Dwelling Elderly Individuals,"The aim of our study was to investigate the effects of silent brain lesions on cognitive function of community-dwelling elderly individuals. Brain magnetic resonance imaging and other medical examinations were performed on 350 nondemented elderly individuals (121 male and 229 female, average age 72.4 years) who resided in the rural community of Sefuri Village, Saga, Japan. The mini mental state examination and modified Stroop test (MST) were used to identify cognitive impairment. White matter lesions (WMLs) and cerebral atrophy on magnetic resonance imaging were measured quantitatively. Multivariate analyses were done using a logistic regression model with a software package. Cognitive impairment defined by mini mental state examination score less than 24 was present in 55 individuals (15.7%). They had a lower educational level, significantly larger quantity of WMLs, and more remarkable cerebral atrophy. Frontal lobe dysfunction was detected in 52 individuals (14.9%) through prolonged MST score (>36 seconds). Impaired frontal lobe function was related to number of silent lacunar infarcts, larger WMLs, and more prominent cerebral atrophy. MST score in individuals with two or more infarcts was significantly more prolonged compared with MST score in those without infarction. These results suggest that WMLs may cause rather diffuse cognitive decline, whereas multiple lacunar infarcts are specifically involved in frontal lobe dysfunction. Silent ischemic lesions in apparently healthy elderly individuals seem to form a distinctive group of people with vascular cognitive impairment without dementia. This group should be the primary target of prevention of vascular dementia. © 2009 National Stroke Association.",,"Koga, H.;Takashima, Y.;Murakawa, R.;Uchino, A.;Yuzuriha, T.;Yao, H.",2009,January,,0,
3248,Malignant cerebral edema related to Systemic Lupus Erythematosus,"Background The neurological manifestations of Systemic Lupus Erythematosus (SLE) are varied and incompletely described. A few case series report a benign idiopathic intracranial hypertension (IIH) related to SLE, which is responsive to immunotherapy. There are limited reports of patients with malignant cerebral edema, and diffuse white matter changes in the absence of central nervous system (CNS) vasculitis. Methods Case series from our tertiary care center and review of the relevant literature. Results Case one was a 32 year-old woman admitted with nausea, vomiting and cranial nerve palsies. Serology was significant for a diagnosis of probable SLE. MRI was performed and showed bilateral symmetric diffuse T2/FLAIR hyperintensities throughout the white matter and cerebral angiography was unremarkable. The patient developed recalcitrant cerebral edema with intracranial hypertension despite immunosuppressive therapies and subsequently expired. Post mortem evaluation showed a white matter inflammatory process, but no vascular changes consistent with CNS vasculitis. Case two was a 29 year-old woman with known SLE that presented with a loss of consciousness. Imaging included a CT that showed diffuse cerebral edema with white matter involvement and a normal cerebral angiogram. Again, despite maximal medical management the patient herniated resulting in death by neurologic criteria. Conclusions These two cases represent a syndrome of white matter changes and diffuse cerebral edema associated with SLE that have yet to be reported in the literature. It is unclear if this process has a similar pathology to SLE related IIH. Because this syndrome causes a fulminant cerebral edema, further research is needed to better understand the underlying pathology and identify potential treatment options.",,"Koffman, L.;Prayson, R.;Manno, E. M.",2016,15,,0,
3249,An elderly case with sarcoidosis whose symptom of dementia was effectively treated by steroid,"We report a case of a 74-year-old woman whose symptoms of dementia may have been caused by sarcoidosis and in whom steroid treatment was effective. The patient, who had recieved treatment for hypertension, started to exhibit symptoms of dementia one year previously and progressively deteriorated during the month before she was admitted. Brain computed tomography showed multiple lacunae infarctions. Chest X-ray showed mild swelling of bilateral lymph nodes in the mediastinum. The patient was referred to an ophthalmologist because of complaints of disturbed visual field, and bilateral uveitis was diagnosed. Negative tuberculin, high serum ACE value and high absorbance in the lung hila on Ga scintigram were recognized. Lymph node biopsy revealed typical granuloma compatible with sarcoidosis. Cerebrospinal fluid (CSF) showed elevated protein concentration without an increased cell count. EEG showed a diffuse slow wave pattern. We observed the progression of dementia shown by declining scores of Mini-Mental State Examination (MMSE) from 17/30 on admission to 7/30 on day 30 after admission. Although enhanced MRI of the brain showed no typical findings of sarcoidosis, we started treatment with prednisolone (50 mg/day) based on the suspicion that the progression of dementia was caused by sarcoidosis. One month after the start of steroid treatment, we observed gradual improvement of symptoms. The MMSE score increased to 20/30. According to previous reports, elderly sarcoidosis patients relatively rare by show dementia, but sarcoidosis should be considered in the differential diagnosis because steroid treatment can be effective.",antiinflammatory agent;prednisolone;aged;article;biopsy;case report;dementia;electroencephalography;female;human;lymph node;pathology;sarcoidosis,"Kodama, M.;Umegaki, H.;Mogi, N.;Iguchi, A.;Takeda, A.",2002,,,0,
3250,Relationship among neuroimaging indices of cerebral health during normal aging,"Sensitive measures of brain aging show great promise for gauging factors that affect aging and degenerative processes, such as risk genes or therapy. Here we examined age-related trends for three indices of cerebral health: gyral gray matter (GM) thickness, dilation of sulcal spaces with CSF, and the volume of T2-hyperintense white matter (HWM) lesions. The study involved 31 healthy adults age 57-82 years old. Measurements of average GM thickness, average sulcal span and HWM volume were performed using high-resolution 3D T1- and T2-weighted brain MR images. Age-related trends for the three cerebral health indices were consistent with previously published work though the analysis of their covariance led to a previously unreported relationship. Simultaneous multiple regression found that dilation of cortical sulci were primarily (t = 2.59, P < 0.01) related to the increases in HWM volume and secondarily related (t = -2.51, P < 0.01) to the reductions of the cortical GM thickness. The are-corrected correlation between reduction in GM thickness and increases in HWM volume, was not significant (P = 0.34). These findings are of interest in designing quantitative measures of brain aging for monitoring individual patients and in large-scale clinical trials.","Aged;Aged, 80 and over;Aging/ pathology;Atrophy/etiology/ pathology/physiopathology;Brain Mapping;Cerebral Cortex/ pathology/physiopathology;Dementia/pathology/physiopathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Kochunov, P.;Thompson, P. M.;Coyle, T. R.;Lancaster, J. L.;Kochunov, V.;Royall, D.;Mangin, J. F.;Riviere, D.;Fox, P. T.",2008,Jan,10.1002/hbm.20369,0,
3251,Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling,"Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large ""mega-family"". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability. © 2014 Elsevier Inc.",,"Kochunov, P.;Jahanshad, N.;Sprooten, E.;Nichols, T. E.;Mandl, R. C.;Almasy, L.;Booth, T.;Brouwer, R. M.;Curran, J. E.;de Zubicaray, G. I.;Dimitrova, R.;Duggirala, R.;Fox, P. T.;Elliot Hong, L.;Landman, B. A.;Lemaitre, H.;Lopez, L. M.;Martin, N. G.;McMahon, K. L.;Mitchell, B. D.;Olvera, R. L.;Peterson, C. P.;Starr, J. M.;Sussmann, J. E.;Toga, A. W.;Wardlaw, J. M.;Wright, M. J.;Wright, S. N.;Bastin, M. E.;McIntosh, A. M.;Boomsma, D. I.;Kahn, R. S.;den Braber, A.;de Geus, E. J. C.;Deary, I. J.;Hulshoff Pol, H. E.;Williamson, D. E.;Blangero, J.;van 't Ent, D.;Thompson, P. M.;Glahn, D. C.",2014,2014,,0,
3252,Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain,"Objectives: The thickness of the brain's cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. Methods: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 ± 13.2 years) recruited from 73 (9.7 ±9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. Results: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD ≥3.0) QTLs were localized within chromosome 15q22-23. More detailed localization reported no significant association (p <5.10-5) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p ≤ 10-3) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer's disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p <0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p < 0.05) but failed to show a significant correlation (p = 0.09) with FA. Discussion: This study identified a novel, significant QTL at 15q22-23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM-FA values. © 2011 Kochunov, Glahn, Nichols, Winkler, Hong, Holcomb, Stein, Thompson, Curran, Carless, Olvera, Johnson, Cole, Kochunov, Kentand Blangero.",ADAM10 endopeptidase;n methyl dextro aspartic acid receptor;n methyl dextro aspartic acid receptor regulated 2;retinoid related orphan receptor alpha;unclassified drug;adult;aged;Alzheimer disease;article;brain cortex;brain water;chromosome 15q;cortical gray matter thickness;diffusion;diffusion tensor imaging;family study;female;fractional anisotropy;gene expression;gene identification;gene location;genetic analysis;genetic association;genetic trait;genotype;gray matter;Hispanic;human;leukocyte;male;nervous system parameters;neuroimaging;normal human;nuclear magnetic resonance imaging;phenotype;pleiotropy;post hoc analysis;quantitative trait locus;single nucleotide polymorphism,"Kochunov, P.;Glahn, D. C.;Nichols, T. E.;Winkler, A. M.;Hong, E. L.;Holcomb, H. H.;Stein, J. L.;Thompson, P. M.;Curran, J. E.;Carless, M. A.;Olvera, R. L.;Johnson, M. P.;Cole, S. A.;Kochunov, V.;Kent, J.;Blangero, J.",2011,,10.3389/fnins.2011.00120,0,3253
3253,Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain,"OBJECTIVES: The thickness of the brain's cortical gray matter (GM) and the fractional anisotropy (FA) of the cerebral white matter (WM) each follow an inverted U-shape trajectory with age. The two measures are positively correlated and may be modulated by common biological mechanisms. We employed four types of genetic analyses to localize individual genes acting pleiotropically upon these phenotypes. METHODS: Whole-brain and regional GM thickness and FA values were measured from high-resolution anatomical and diffusion tensor MR images collected from 712, Mexican American participants (438 females, age = 47.9 +/- 13.2 years) recruited from 73 (9.7 +/- 9.3 individuals/family) large families. The significance of the correlation between two traits was estimated using a bivariate genetic correlation analysis. Localization of chromosomal regions that jointly influenced both traits was performed using whole-genome quantitative trait loci (QTL) analysis. Gene localization was performed using SNP genotyping on Illumina 1M chip and correlation with leukocyte-based gene-expression analyses. The gene-expressions were measured using the Illumina BeadChip. These data were available for 371 subjects. RESULTS: Significant genetic correlation was observed among GM thickness and FA values. Significant logarithm of odds (LOD >/= 3.0) QTLs were localized within chromosome 15q22-23. More detailed localization reported no significant association (p < 5.10(-5)) for 1565 SNPs located within the QTLs. Post hoc analysis indicated that 40% of the potentially significant (p </= 10(-3)) SNPs were localized to the related orphan receptor alpha (RORA) and NARG2 genes. A potentially significant association was observed for the rs2456930 polymorphism reported as a significant GWAS finding in Alzheimer's disease neuroimaging initiative subjects. The expression levels for RORA and ADAM10 genes were significantly (p < 0.05) correlated with both FA and GM thickness. NARG2 expressions were significantly correlated with GM thickness (p < 0.05) but failed to show a significant correlation (p = 0.09) with FA. DISCUSSION: This study identified a novel, significant QTL at 15q22-23. SNP correlation with gene-expression analyses indicated that RORA, NARG2, and ADAM10 jointly influence GM thickness and WM-FA values.",,"Kochunov, P.;Glahn, D. C.;Nichols, T. E.;Winkler, A. M.;Hong, E. L.;Holcomb, H. H.;Stein, J. L.;Thompson, P. M.;Curran, J. E.;Carless, M. A.;Olvera, R. L.;Johnson, M. P.;Cole, S. A.;Kochunov, V.;Kent, J.;Blangero, J.",2011,,10.3389/fnins.2011.00120,0,
3254,18F-florbetapir PET in patients with frontotemporal dementia and Alzheimer disease,"Pathologic deposition of amyloid beta (Abeta) protein is a key component in the pathogenesis of Alzheimer disease (AD) but not a feature of frontotemporal dementia (FTD). PET ligands for Abeta protein are increasingly used in diagnosis and research of dementia syndromes. Here, we report a PET study using (18)F-florbetapir in healthy controls and patients with AD and FTD. METHODS: Ten healthy controls (mean age +/- SD, 62.5 +/- 5.2 y), 10 AD patients (mean age +/- SD, 62.6 +/- 4.5), and 8 FTD patients (mean age +/- SD, 62.5 +/- 9.6) were recruited to the study. All patients underwent detailed clinical and neuropsychologic assessment and T1-weighted MR imaging and were genotyped for apolipoprotein E status. All participants underwent dynamic (18)F-florbetapir PET on a high-resolution research tomograph, and FTD patients also underwent (18)F-FDG PET scans. Standardized uptake value ratios (SUVRs) were extracted for predefined gray and white matter regions of interest using cerebellar gray matter as a reference region. Static PET images were evaluated by trained raters masked to clinical status and regional analysis. RESULTS: Total cortical gray matter (18)F-florbetapir uptake values were significantly higher in AD patients (median SUVR, 1.73) than FTD patients (SUVR, 1.13, P = 0.002) and controls (SUVR, 1.26, P = 0.04). (18)F-Florbetapir uptake was also higher in AD patients than FTD patients and controls in the frontal, parietal, occipital, and cingulate cortices and in the central subcortical regions. Only 1 FTD patient (homozygous for apolipoprotein E epsilon4) displayed high cortical (18)F-florbetapir retention, whereas (18)F-FDG PET demonstrated mesiofrontal hypometabolism consistent with the clinical diagnosis of FTD. Most visual raters classified 1 control (10%) and 8 AD (80%) and 2 FTD (25%) patients as amyloid-positive, whereas ratings were tied in another 2 FTD patients and 1 healthy control. CONCLUSION: Cortical (18)F-florbetapir uptake is low in most FTD patients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, with a higher rate of discordance between interpreters than in AD and control subjects.",Aged;Alzheimer Disease/diagnosis/genetics/ radionuclide imaging;Amyloidogenic Proteins/chemistry;Aniline Compounds;Apolipoproteins E/genetics;Case-Control Studies;Ethylene Glycols;Female;Fluorine Radioisotopes;Frontotemporal Dementia/diagnosis/ radionuclide imaging;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography,"Kobylecki, C.;Langheinrich, T.;Hinz, R.;Vardy, E. R.;Brown, G.;Martino, M. E.;Haense, C.;Richardson, A. M.;Gerhard, A.;Anton-Rodriguez, J. M.;Snowden, J. S.;Neary, D.;Pontecorvo, M. J.;Herholz, K.",2015,Mar,10.2967/jnumed.114.147454,0,
3255,Influences of asymptomatic cerebral lesions on cognitive function,"Lacunar infarction, leukoaraiosis, état criblé and cerebral atrophy increase in incidence and severity with age. They are believed to be essentially ""asymptomatic"", when observed in aged subjects, who are free of serious neurological symptoms. To assess the influences of these cerebral lesions on cognitive functions in the aged subjects, we evaluated MRI findings and the Hamamatsu psychological battery for higher cerebral function. Out of 127 participants in the present study, 42 (33.1%) showed mild to severe impaired cognitive function. Leukoaraiosis (β = 0.267, p = 0.014) and cerebral atrophy (β = 0.182, p = 0.038) correlated well with the impairment, whereas lacunar infarction and état criblé seemed to have no effects on cognitive function. Adequate control of risk factors for leukoaraiosis and cerebral atrophy might prevent cognitive impairment.",age;aged;aging;article;brain atrophy;brain function;brain infarction;brain injury;cognitive defect;female;human;incidence;leukoaraiosis;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance imaging;psychologic test;risk factor;symptom,"Kobota, M.;Saeki, N.;Yamaura, A.;Nakazaki, S.;Kusaka, T.",2001,,,0,
3256,Clinical evaluation of dementia,"The diagnosis of dementia is a clinical one that can only be made with the rigorous use of clearly defined diagnostic criteria in an interview setting. The diagnosis cannot be made by laboratory tests or imaging techniques alone. In the elderly, a number of other psychiatric syndromes must be distinguished from dementia, including delirium, psychosis, depression, and mania. Sometimes it is not possible to make this distinction with confidence. Most dementias are caused by Alzheimer's disease or multi-infarct dementia, and the probable etiologic diagnosis can be made fairly quickly. However, a number of etiologies are possible, and some patients require extensive study. Some uncertainty is usual in the diagnosis of the living patient because routine brain biopsy is not feasible. Geropsychiatric and neurologic consultants can be helpful in selected cases.",,"Koblenzer, J.",1993,Nov,,0,
3257,Cerebral amyloid angiopathy complicated by multiple cerebral infarcts and intracerebral hemorrhages: case report,"Recently, cerebral amyloid angiopathy is stressed as an unusual and infrequent cause of cerebral infarct or intracerebral hemorrhage. This report described a case of cerebral amyloid angiopathy complicated by multiple cerebral infarcts and multiple intracerebral hemorrhages. This 70-year-old man was admitted to our hospital on November 10, 1984 for evaluation of the gradual onset of dysarthria. Examination showed only slight dysarthria. There was no history of hypertension or dementia. A computed tomography (CT) showed enlarged ventricles with cortical atrophy and multiple low-density lesions, deep in the left frontal, left parietal, right parietal lobes, and in the both basal ganglias. The patient discharged from the hospital with only slight dysarthria. On November 20, 1984, he was admitted to our hospital again, because he was found unresponsive on the floor. He was somnolent but arousable. Examination showed disorientation, impairment of recent memory and impairment of calculation, A CT scan demonstrated three small intracerebral hemorrhages in the left frontal, right parietal lobes and left basal ganglia. On the fifth hospital day he deteriorated acutely, becoming semicomatose and hemiparetic on the right side. A repeated CT scan showed two new intracerebral hemorrhages in the left frontal lobe. Cerebral angiograms showed only minimal changes due to the occupying lesions in the above mentioned area. The hematomas was evacuated via left fronto-parietal craniotomy. The specimens removed with hematoma (stained with hematoxylin-eosin, Congo red and thioflavin T) showed extensive amyloid angiopathy. Postoperatively he made a good recovery, although he had residual mental dysfunctions. He expired by pneumonia on March 30, 1985.(ABSTRACT TRUNCATED AT 250 WORDS)",amyloid;aged;article;brain artery;brain hemorrhage;brain infarction;case report;cerebrovascular disease;human;male;metabolism;pathology,"Kobayashi, Y.;Suematsu, K.;Kamada, H.;Shitamichi, M.;Matsuzaki, T.;Nakamura, J.",1987,,,0,
3258,Prospective study on the influence of social activity on development of dementia in the neurologically normal elderly,"We investigated the rate of development of dementia in 84 neurologically normal elderly subjects living in an old-age home (30 subjects, mean 77.2 years) or their own home 954, 73.7) prospectively. We examined cerebral blood flow (CBF), Hasegawa's scale (HS) and Kohs' block design test 6 to 9 years before this study (1991). HS and Kohs' IQ were significantly lower in the old-age home group than that in their own home group at that time. However, there were no demented subjects. Mortality was 21%, and we confirmed 9 dementia and 6 stroke cases during the period of observation. Twenty-seven percent of the old-age home group showed dementia in 1991. This rate was significantly higher than that for the elderly living in their own home (6.7%). Occurrence of stroke was also significantly higher in the former group than in the latter group. The subjects who developed stroke during observation showed a high incidence of dementia. Mean CBF measured on the first examination was significantly lower in dementia cases with stroke than in dementia cases without it. We performed MRI in 4 demented cases in 1991 (Fig. 1). Two cases showed no significant lesions and the other cases showed cerebral infarction which could cause dementia. These results indicate that life style and social environment may have significant effect on aging of the brain and on development of dementia in the elderly.",aged;article;brain blood flow;brain infarction;clinical trial;controlled clinical trial;controlled study;dementia;human;lifestyle;normal human;social environment;cerebrovascular accident,"Kobayashi, S.;Yamaguchi, S.;Koide, H.;Okada, K.;Kitani, M.;Yamashita, K.;Bokura, H.",1994,,,0,
3259,Relationship between silent brain infarction and chronic kidney disease,"Background. The presence of silent brain infarction (SBI) increases the risk of symptomatic stroke and dementia. The association between SBI and chronic kidney disease (CKD) has not been clarified. Moreover, little is known about what factors are related to SBI in CKD patients and whether the prevalence of SBI differs in CKD stage or cause of CKD. Methods. This is a cross-sectional study. A total of 375 subjects - 335 with CKD and 40 with essential hypertension - were included. All subjects underwent magnetic resonance imaging (MRI) of the brain to detect SBI. Glomerular filtration rate (GFR) was estimated using Modification of Diet in Renal Disease equation, and cardiovascular risk factors were examined. Results. The prevalence of SBI was 56.5% in all subjects. Among causes of CKD, hypertensive nephrosclerosis had a strong association with SBI. According to the estimated GFR (eGFR) stage, the more severe the stage of eGFR, the higher the prevalence of SBI (age-adjusted odds ratio [95% confidence interval] for eGFR 30-59, 15-29 and <15 versus ≥60 mL/min/1.73 m (2): 1.34 [0.68-1.99], 1.94 [1.30-2.57] and 2.51 [1.91-3.10]). In multivariate logistic analysis, eGFR was related to SBI independently, in addition to age and blood pressure (P = 0.025). However, other traditional and non-traditional risk factors were not. Conclusion. There was an independent association between eGFR and SBI. CKD patients should receive active detection of SBI and more intensive preventive management, especially for hypertension, should be needed in CKD patients to prevent SBI. © The Author [2008].",,"Kobayashi, M.;Hirawa, N.;Yatsu, K.;Kobayashi, Y.;Yamamoto, Y.;Saka, S.;Andoh, D.;Toya, Y.;Yasuda, G.;Umemura, S.",2009,January,,0,
3260,Report of three cases of Alzheimer's disease with focal motor symptoms: clinical correlates of neuroimaging findings,"We report clinical and neuroimaging findings for three patients suffering from Alzheimer's disease (AD) with focal motor symptoms. These patients initially showed cognitive deficits and subsequently featured myoclonus and awkward movements in the unilateral upper limb while progressing to paresis. Paresis was noted in the unilateral upper limb. All patients held the unilateral arm flexed at the wrist and elbow, closely adducted to the body and the hand fisted and pronated. No signs of cerebellar ataxia, sensory disturbance or long tract signs were observed, nor any of the initial non-cognitive behavioural changes typical of frontotemporal dementia. EEGs of these patients showed marked slowing of basic activity without epileptic discharges. MRIs showed progressive brain atrophy in the contralateral frontoparietal lobes as well as the hippocampal formation. Cases 2 and 3 featured extensive long T2 lesions on MRI. 99mTc-HMPAO-SPECT revealed blood flow hypoperfusion in the corresponding regions. The cerebellum and brain stem showed neither morphological abnormalities nor blood flow hypoperfusion. On the basis of these clinical and neuroimaging observations, the focal motor symptoms were attributed to contralateral frontoparietal cortical atrophy with or without white matter lesion.",diagnostic agent;hexamethylpropyleneamine oxime;oxime;radiopharmaceutical agent;aged;Alzheimer disease;article;atrophy;brain;brain circulation;case report;cognitive defect;female;human;male;middle aged;nuclear magnetic resonance imaging;pathology;physiology;psychomotor disorder;single photon emission computer tomography;vascularization,"Kobayashi, K.;Shimoda, K.;Higashima, M.;Nakano, H.;Miyazu, K.;Hayashi, M.;Tabata, O.;Koshino, Y.",2000,,,0,
3261,Leukoencephalopathy with cognitive impairment following tocilizumab for the treatment of rheumatoid arthritis (RA),"The biological agent tocilizumab, is a humanized, anti-human interleukin-6 receptor antibody. A 72-year-old woman developed cognitive impairment during the Phase III clinical trial of tocilizumab for the treatment of rheumatoid arthritis. MRI demonstrated hyperintense dissemination throughout the white matter on T2WI. An initial diagnosis of possible progressive multifocal leukoencephalopathy was made, but the PCR for JC virus DNA was negative in the CSF. The leukoencephalopathy might have been caused by a mechanism related to tocilizumab itself. It is strongly recommended to perform MRI if a patient develops any cognitive impairment during tocilizumab therapy. © 2009 The Japanese Society of Internal Medicine.",antinuclear antibody;tocilizumab;hemoglobin A1c;immunoglobulin G;prednisolone;rheumatoid factor;stromelysin;virus DNA;achilles reflex;aged;ankylosis;antibody blood level;article;behavior disorder;brain function;case report;cerebrospinal fluid analysis;cognitive defect;computer assisted tomography;dementia;drug efficacy;drug withdrawal;edema;electroencephalography;enzyme blood level;female;hemoglobin blood level;human;immunoglobulin blood level;JC virus;leukoencephalopathy;Mini Mental State Examination;nuclear magnetic resonance imaging;physical examination;polymerase chain reaction;rheumatoid arthritis;speech disorder,"Kobayashi, K.;Okamoto, Y.;Inoue, H.;Usui, T.;Ihara, M.;Kawamata, J.;Miki, Y.;Mimori, T.;Tomimoto, H.;Takahashi, R.",2009,,,0,
3262,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy without anterior temporal pole involvement: A case report,"The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-year-old man with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence of migraine with aura in subjects with CADASIL is several times greater than that in the general population. Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine with atypical aura, even in the absence of white matter lesion in the ATPs. © 2014 by National Stroke Association.",Notch3 receptor;adult;article;autosomal dominant disorder;basal ganglion;brain infarction;CADASIL;case report;cerebellum;cerebral artery disease;dizziness;dysarthria;exon;headache;human;leukoencephalopathy;male;medical history;middle aged;migraine with aura;nuclear magnetic resonance imaging;point mutation;priority journal;weakness,"Kobayashi, J.;Sato, S.;Okumura, K.;Miyashita, F.;Ueda, A.;Ando, Y.;Toyoda, K.",2014,,,0,
3263,Local cerebral blood flow in motor neuron disease: Correlation with clinical findings,"Local cerebral blood flow (CBF) measured by xenon-enhanced CT was correlated with the clinical findings in 21 patients with motor neuron disease (mean ± SD age, 60 ± 10 years). In 11 patients, CBF was also measured after intravenous injection of 2 mg thyrotropin releasing hormone (TRH). There were no significant differences in CBF of the cerebral cortex, basal ganglia, thalamus, and subcortical white matter with respect to age, duration of illness, or presence (n = 9) or absence (n = 12) of bulbar palsy. In patients with upper motor neuron disturbance (n = 10), however, local CBF in the frontal cortex was significantly lower (p < 0.05) than in those without it (n = 11). Within the frontal cortex, CBF reduction was marked in the upper posterolateral part (p < 0.05) that included the motor and premotor areas. Intravenous administration of TRH did not significantly alter the local CBF in any of the brain regions examined. An additional patient with motor neuron disease and severe dementia showed marked CBF reduction in the frontal lobe, which was in common with but much greater than the reduction in those exhibiting subcortical dementia (e.g., progressive supranuclear palsy). We conclude that in motor neuron disease patients with upper motor neuron involvement, the selective reduction of CBF in brain regions that include primary motor and premotor areas may reflect functional disturbance or neuronal degeneration in these regions. The ameliorating effect of TRH in patients with motor neuron disease, if any, appears not to be related to increases in local CBF or activation of brain function.",protirelin;xenon;adult;aged;amyotrophic lateral sclerosis;article;brain blood flow;clinical article;dementia;female;human;intravenous drug administration;male;motor neuron disease;priority journal,"Kobari, M.;Obara, K.;Watanabe, S.;Dembo, T.;Fukuuchi, Y.",1996,,,0,
3264,Familial idiopathic brain calcification with autosomal dominant inheritance,"We report a family with brain calcification, predominantly in the basal ganglia, and no evident cause such as abnormal calcium or phosphorus metabolism. The proband, a 48-year-old man, had intellectual decline, parkinsonism, and mild cerebellar ataxia. He had bilateral and symmetric calcification of the basal ganglia, thalamus, dentate nucleus, cerebral cortex, subcortical white matter, and hippocampus on CT. Calcified areas showed low- or high-intensity signals on MRI T(1)-weighted images, and low- intensity signals on MRI T(2)-weighted images. Two sons and both parents, all asymptomatic, also showed calcification of the basal ganglia, suggesting an autosomal dominant inheritance. Familial idiopathic brain calcification is a rare disorder with less than 20 previously reported families. Twelve families with autosomal dominant inheritance showed a relatively homogeneous clinical picture, which may represent a distinct clinical entity. Mental deterioration, parkinsonism, and cerebellar ataxia appear in adult life and progress gradually. CT imaging, rather than MRI, is a simple and useful means to screen family members for this condition.",,"Kobari, M.;Nogawa, S.;Sugimoto, Y.;Fukuuchi, Y.",1997,March,,0,
3265,"Leukoaraiosis: correlation of MR and CT findings with blood flow, atrophy, and cognition","Hypodense periventricular white-matter lesions detected by CT (leukoaraiosis) and high-intensity T2 signals detected by MR imaging were correlated with measurements of local cerebral blood flow (LCBF), cerebral atrophy, and cognitive performance. Subjects studied included elderly volunteers who were neurologically normal (n = 6), patients with chronic cerebral infarctions and intact cognition (n = 2), patients with multiinfarct dementia (n = 14), and patients with Alzheimer dementia (n = 9). Leukoaraiosis correlated with periventricular high-intensity lesions detected by MR, LCBF reductions, cognitive impairments, and cerebral atrophy. Moderate to severe leukoaraiosis was associated with LCBF reductions in the cortex, basal ganglia, and frontal white matter. Periventricular MR lesions correlated with cerebral atrophy but not with cognitive impairments or reductions in LCBF. The exquisite sensitivity of MR revealed small lesions that did not correlate with LCBF reductions and cognitive impairments. Remote subcortical white-matter lesions detected by MR did not correlate with periventricular MR lesions, leukoaraiosis, LCBF, cerebral atrophy, or cognitive performance, indicating little clinical relevance. We concluded that diffuse cerebral hypoperfusion, particularly in combination with the poor collateral circulation of white matter surrounding the lateral ventricles, is responsible for leukoaraiosis.","Aged;Alzheimer Disease/diagnosis;Atrophy;Brain/ pathology;Cerebral Infarction/diagnosis;Cerebrovascular Circulation;Cognition Disorders/etiology;Dementia, Multi-Infarct/diagnosis;Demyelinating Diseases/complications/ diagnosis;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Kobari, M.;Meyer, J. S.;Ichijo, M.;Oravez, W. T.",1990,Mar-Apr,,0,
3266,Distinguishing patients with senile dementia of Alzheimer type and normal elderly subjects utilizing xenon CT-CBF and multivariate analysis,"Local cerebral blood flow (LCBF) was measured in 17 patients with senile dementia of Alzheimer type (SDAT) and 17 normal controls, utilizing stable xenon computed tomography (Xe CT-CBF). In patients with SDAT, LCBF values were decreased in the cerebral cortex and subcortical structures including the thalamus, basal ganglia and white matter of both hemispheres. Linear discriminant function analysis of LCBF values separated patients with SDAT from normal elderly subjects, with an error of 8.8%. Variables helpful in distinguishing SDAT patients from normal subjects were LCBF values for the frontal and temporal cortex. Multiple regression equation for predicting cognitive performance scores from LCBF values showed the best correlations with LCBF values for the frontal and occipital cortex and thalamus. Xe CT-CBF measurements provide useful information concerning diagnosis and brain function in patients with SDAT.","Aged;Aging/physiology;Alzheimer Disease/diagnosis/*physiopathology/radiography;Case-Control Studies;*Cerebrovascular Circulation;Female;Humans;Male;Middle Aged;Multivariate Analysis;Tomography, X-Ray Computed/methods;Xenon","Kobari, M.;Meyer, J. S.;Ichijo, M.;Kawamura, J.",2000,Feb,,0,
3267,Xenon contrast CT-CBF measurements in senile dementia of Alzheimer type,"Local cerebral blood flow (LCBF) was measured among 17 patients with senile dementia of the Alzheimer type (SDAT) utilizing stable xenon contrasted computed tomography-cerebral blood flow (Xe CT-CBF). Results were compared with 17 elderly neurologically normal controls. In patients with SDAT, LCBF values were decreased symmetrically in cerebral cortex and subcortical structures. LCBF reductions were most marked in cerebral cortex (-25.7%) with lesser reductions in subcortical gray (-15.8%) and white matter (-16.3%). Frontotemporal cortical regions showed greatest LCBF reductions. Linear discriminant function analysis of LCBF values separated patients with SDAT from elderly normal volunteers, with an error of 8.8%. Variables helpful in discriminating SDAT patients from normal volunteers were LCBF values for frontal and temporal cortex. Multiple regression equation for predicting cognitive performance scores from LCBF values showed best correlations with LCBF values for frontal and occipital cortex and thalamus.",xenon;adult;aged;Alzheimer disease;article;brain blood flow;clinical article;computer assisted tomography;dementia;female;human;male;multivariate analysis,"Kobari, M.;Meyer, J. S.;Ichijo, M.;Kawamura, J.",1992,,,0,
3268,"Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal aging","To elucidate the role of leuko-araiosis observed on computed tomographic imaging among normal populations, 37 neurologically and cognitively normal volunteers ages 18 to 88 years were studied. Local cerebral blood flow was measured using stable xenon-enhanced computed tomography. Severity of leuko-araiosis and cerebral atrophy were graded on computed tomographic images. Leuko-araiosis was observed in 21.6% of normal volunteers, in 52.2% of patients with multi-infarct dementia (n = 23), and in 61.5% of patients with dementia of the Alzheimer type (n = 13). When multiple regression analysis was applied among normal volunteers, the degree of cerebral atrophy, advancing age, and local cerebral blood flow reductions of subcortical white matter correlated and contributed in that order of precedence to the presence and severity of leuko-araiosis. Combination of the unusual vascular anatomy of periventricular white matter together with cerebral hypoperfusion appears to be related to the occurrence of leuko-araiosis observed among neurologically and cognitively normal subjects. Further investigations should determine whether leuko-araiosis among this population is a risk factor for later cognitive impairments.","Adolescent;Adult;Aged;Aged, 80 and over;Aging/ physiology;Alzheimer Disease/pathology/physiopathology;Atrophy;Brain/ pathology/radiography;Cerebrovascular Circulation;Dementia, Multi-Infarct/pathology/physiopathology;Female;Humans;Male;Middle Aged;Reference Values;Tomography, X-Ray Computed","Kobari, M.;Meyer, J. S.;Ichijo, M.",1990,Feb,,0,
3269,Influence of statin therapy at time of stroke onset on functional outcome among patients with atrial fibrillation,"Background Statin pretreatment has been associated with reduced infarct volume in nonlacunar strokes. The effect of statins on functional outcomes of strokes related to atrial fibrillation (AF) is unknown. We aimed to define the influence of prestroke statin use on functional outcome in AF. Methods We assembled a cohort of consecutive ischemic stroke patients from 2006 to 2010. All patients underwent CT or MRI and were adjudicated by site investigators. AF was confirmed by electrocardiogram in 100% of patients. Site neurologists blinded to the study hypothesis affirmed the type of stroke and assessed the severity of disability at the time of hospital discharge. The frequency of death at 30-days was calculated. Results Ischemic stroke (n = 1030) resulted in a severe neurological deficit or death (modified Rankin scale > 4) at 30 days in 711 patients (69%). Using multivariable logistic regression models adjusting for factors associated with statin treatment and factors associated with functional outcome, prestroke statin use was associated with a 32% reduction in frequency of severe stroke (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50-0.92; P = 0.011). Other independent factors associated with severe stroke included older age, female sex, non-White race, diabetes mellitus, prior ischemic stroke, prior venous thromboembolism, and dementia. Conclusion Ischemic strokes in AF are associated with high mortality and morbidity. Statin use at time of stroke onset among patients with AF was associated in this study with less severe stroke and warrant validation. Copyright 2016 Elsevier Ireland Ltd",aged;article;atrial fibrillation;brain ischemia;cerebrovascular accident dt [Drug Therapy];computer assisted tomography;controlled study;death;disability;disease severity;electrocardiogram;female;functional assessment;hospital discharge;human;major clinical study;male;multivariate logistic regression analysis;nuclear magnetic resonance imaging;outcome assessment;priority journal;Rankin scale;hydroxymethylglutaryl coenzyme A reductase inhibitor dt [Drug Therapy];clinical trial;confidence interval;controlled clinical trial;dementia;diabetes mellitus;disability severity;drug therapy;logistic regression analysis;morbidity;mortality;neurologist;odds ratio;race;risk factor;single blind procedure;stroke patient;validation process;venous thromboembolism;hydroxymethylglutaryl coenzyme A reductase inhibitor,"Ko, D.;Thigpen, J. L.;Otis, J. A.;Forster, K.;Henault, L.;Quinn, E.;Tripodis, Y.;Berger, P. B.;Limdi, N.;Hylek, E. M.",2017,,,0,
3270,"Survival study of vascular dementia in Rochester, Minnesota","OBJECTIVE: To investigate the relationship between features and definitions of vascular dementia (VaD) and survival. DESIGN: We used the medical records linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease were defined using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Vascular dementia was defined by ad hoc criteria, including imaging. Each patient with dementia was matched by age and sex to a referent subject free of dementia. Patients with dementia and referent subjects were followed from the onset of dementia (or index year) through death, censoring, or the end of the study. RESULTS: We included 479 patients with incident dementia and 479 referent subjects. Overall, patients with VaD had worse mortality than referent subjects (relative risk [RR], 2.7; 95% confidence interval [CI], 1.9-3.9). Among patients with VaD, those with dementia temporally related to a stroke had a worse relative mortality (RR, 4.5; 95% CI, 2.7-7.4) than those with only imaging evidence of bilateral infarctions in gray matter structures (RR, 2.4; 95% CI, 1.5-3.8). Relative mortality estimates varied by using 3 sets of published diagnostic criteria for VaD. Patients with VaD had a higher RR of death (RR, 2.7; 95% CI, 1.9-3.9) than patients with dementia overall (RR, 1.8; 95% CI, 1.6-2.1) or patients with Alzheimer disease (RR, 1.4; 95% CI, 1.2-1.7). CONCLUSIONS: The relative mortality of patients with VaD varied depending on the set of diagnostic criteria used. A temporal relationship to a stroke was the strongest predictive feature for poor survival in patients with dementia.","Aged;Aged, 80 and over;Dementia, Vascular/ mortality;Female;Humans;Incidence;Male;Middle Aged;Minnesota/epidemiology;Stroke/mortality;Survival Analysis","Knopman, D. S.;Rocca, W. A.;Cha, R. H.;Edland, S. D.;Kokmen, E.",2003,Jan,,0,
3271,"Incidence of vascular dementia in Rochester, Minn, 1985-1989","Objective: To examine the contribution of cerebrovascular disease to dementia. Methods: We used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, Minn, for 1985 through 1989. We defined dementia using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. To define dementia types, we reviewed neuroimaging reports, which were available for two thirds of dementia cases, in addition to medical histories and neurologic examination results. Vascular dementia (VaD) was defined by 1 of the following criteria: dementia onset or worsening within 3 months of a clinical stroke or bilateral gray matter infarctlike lesions shown by imaging that fulfilled specified location criteria (critical imaging lesions). Results: We found 482 incident cases of dementia. Overall, 10% of patients had onset or worsening of their dementia within 3 months of a stroke. Eleven percent of the incident dementia cases had bilateral gray matter lesions on imaging that were considered critical. Eighteen percent of patients had one or the other of these features (VaD by our criteria), but only 4% of patients had both. The incidence rate of VaD increased steeply with advancing age and was similar in men and women. Our incidence rates were similar to those from a recent European meta-analysis. Conclusion: The presence of either a stroke temporally related to dementia onset or worsening or of critical imaging lesions was common among dementia patients, whereas the occurrence of both features together was rare.",,"Knopman, D. S.;Rocca, W. A.;Cha, R. H.;Edland, S. D.;Kokmen, E.",2002,1,,0,
3272,Vascular dementia in a population-based autopsy study,"Background: The validity of the clinical diagnosis of vascular dementia (VaD) remains suboptimal. Objective: To investigate clinicopathologic correlations in VaD. Methods: We used the medical records-linkage system of the Rochester Epidemiology Project to identify incident cases of dementia in Rochester, Minn, from January 1, 1985, through December 31, 1989. Dementia and Alzheimer disease (AD) were defined by the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Vascular dementia was defined by criteria including imaging results. Pathological characteristics of AD were quantified by means of standard scoring methods for neurofibrillary tangles and neuritic plaques. Vascular pathological findings were assessed by expert neuropathological opinion. Results: Of 419 patients with dementia who died before the study, neuropathological examination results were available in 89 (21%) with median age at onset of 80 years (range, 50-96 years; 52 [58%] women). Pathological diagnoses were",,"Knopman, D. S.;Parisi, J. E.;Boeve, B. F.;Cha, R. H.;Apaydin, H.;Salviati, A.;Edland, S. D.;Rocca, W. A.",2003,1,,0,
3273,Brain injury biomarkers are not dependent on beta-amyloid in normal elderly,"OBJECTIVE: The new criteria for preclinical Alzheimer disease (AD) proposed 3 stages: abnormal levels of beta-amyloid (stage 1), stage 1 plus evidence of brain injury (stage 2), and stage 2 plus subtle cognitive changes (stage 3). However, a large group of subjects with normal beta-amyloid biomarkers have evidence of brain injury; we labeled them as the ""suspected non-Alzheimer pathophysiology"" (sNAP) group. The characteristics of the sNAP group are poorly understood. METHODS: Using the preclinical AD classification, 430 cognitively normal subjects from the Mayo Clinic Study of Aging who underwent brain magnetic resonance (MR), (18)fluorodeoxyglucose (FDG), and Pittsburgh compound B positron emission tomography (PET) were evaluated for FDG PET regional volumetrics, MR regional brain volumetrics, white matter hyperintensity volume, and number of infarcts. We examined cross-sectional associations across AD preclinical stages, those with all biomarkers normal, and the sNAP group. RESULTS: The sNAP group had a lower proportion (14%) with apolipoprotein E epsilon4 genotype than the preclinical AD stages 2 + 3. The sNAP group did not show any group differences compared to stages 2 + 3 of the preclinical AD group on measures of FDG PET regional hypometabolism, MR regional brain volume loss, cerebrovascular imaging lesions, vascular risk factors, imaging changes associated with alpha-synucleinopathy, or physical findings of parkinsonism. INTERPRETATION: Cognitively normal persons with brain injury biomarker abnormalities, with or without abnormal levels of beta-amyloid, were indistinguishable on a variety of imaging markers, clinical features, and risk factors. The initial appearance of brain injury biomarkers that occurs in cognitively normal persons with preclinical AD may not depend on beta-amyloidosis.","Aged;Aged, 80 and over;Biomarkers;Brain/ metabolism/ pathology;Cerebral Cortex/ pathology/radionuclide imaging;Cerebrovascular Disorders/pathology/physiopathology;Female;Fluorodeoxyglucose F18;Humans;Male;Positron-Emission Tomography;Risk Factors;Synucleins/metabolism","Knopman, D. S.;Jack, C. R., Jr.;Wiste, H. J.;Weigand, S. D.;Vemuri, P.;Lowe, V. J.;Kantarci, K.;Gunter, J. L.;Senjem, M. L.;Mielke, M. M.;Roberts, R. O.;Boeve, B. F.;Petersen, R. C.",2013,Apr,10.1002/ana.23816,0,
3274,Invited commentary: Albuminuria and microvascular disease of the brain-A shared pathophysiology,"This commentary considers the implications of the association between albuminuria and cognitive decline described by Jassal et al. in this issue of the Journal (Am J Epidemiol. 2010;171(3):290-291). The authors report that men with albuminuria had a greater likelihood than men without albuminuria of experiencing declines in cognitive function over a 6.6-year period. Albuminuria is the result of endothelial damage in the kidney, which, in turn, is the result of microvascular disease. If one of the key mechanisms of brain microvascular disease is leakage of serum proteins into the brain extracellular space, in a fashion parallel to albuminuria that occurs in nephrosclerosis, several facets of cerebrovascular disease and cognitive decline are explained. First, brain microvascular disease would not be recognized by traditional clinical features of cerebrovascular disease because brain microvascular disease occurs gradually and insidiously. Second, the extravasation of serum proteins as a result of brain microvascular disease would account for the perivascular distribution of white matter hyperintensities on magnetic resonance imaging. Albuminuria might be a useful screening test for generalized microvascular disease and, if detected, might reasonably prompt brain imaging and more intensive therapeutic efforts to forestall further endothelial dysfunction in the kidney, brain, and elsewhere.",,"Knopman, D. S.",2010,February,,0,
3275,Total cerebral blood flow and hippocampal volume in patients with arterial disease. the SMART-MR study,"It has been suggested that compared with other brain tissues, the hippocampus in particular is vulnerable to chronic hypoperfusion. We investigated whether total parenchymal cerebral blood flow (pCBF) was associated with hippocampal atrophy, and also whether this relationship was modified by white matter lesions (WMLs). In a cross-sectional analysis within the SMART-MR (Second Manifestations of ARTerial disease-magnetic resonance) study, which is a cohort study among patients with arterial disease, total CBF (tCBF) and hippocampal volume were assessed in 392 patients (mean age: 629 years, 84% men). Total CBF was expressed in per 100 mL brain volume for obtaining pCBF. Manual volumetric measurements of the hippocampus were carried out on a three-dimensional fast field-echo T1-weighted magnetic resonance imaging scan with isotropic voxels. Automated brain segmentation was used to quantify volumes of the WML and the total brain. A linear regression analysis showed that reduced pCBF was not associated with smaller hippocampal volume after adjustments were made for age and sex. The association attenuated further after additional adjustments were made for vascular risk factors, lacunar infarcts, and WMLs (Β0.01 mL per s.d. decrease in pCBF; 95% confidence interval: 0.06 to 0.08). The association was not modified by WML (P-value for interaction term pCBFWML0.84). We found no evidence of the fact that lower parenchymal blood flow contributes to the neurodegeneration of the hippocampus in a population of patients with arterial disease. © 2009 ISCBFM All rights reserved.",,"Knoops, A. J. G.;Van Der Graaf, Y.;Appelman, A. P. A.;Mali, W. P. T. M.;Geerlings, M. I.",2009,October,,0,
3276,"Sneddon's syndrome, a neurocutaneous disease","The association of livedo racemosa and cerebrovascular lesions is described as Sneddon's syndrome. A 50-year-old female presented livedo racemosa and severe dementia. Cerebral angiography showed irregularities and segmental stenosis of the basic cerebral arteries and almost no filling of their branches. CT revealed atrophy, hydrocephalus and multi-infarct-syndrome. Antiphospholipid antibodies were not detected. Post mortem autopsy showed granular atrophy with development of oligoencephalon and signs of disseminated vasculitis of CNS.",adult;article;case report;computer assisted tomography;dementia;female;human;human tissue;livedo reticularis;Sneddon syndrome;vasculitis,"Knippenberg, D.;Baron, R.;Branczyk, B.;Schluter, E.",1995,,,0,
3277,Quantitative T2 mapping of white matter: applications for ageing and cognitive decline,"In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer's disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.",,"Knight, M. J.;McCann, B.;Tsivos, D.;Dillon, S.;Coulthard, E.;Kauppinen, R. A.",2016,Aug 7,10.1088/0031-9155/61/15/5587,0,
3278,Atrial fibrillation in stroke-free patients is associated with memory impairment and hippocampal atrophy,"Aims: To determine whether atrial fibrillation (AF) in stroke-free patients is associated with impaired cognition and structural abnormalities of the brain. AF contributes to stroke and secondary cognitive decline. In the absence of manifest stroke, AF can activate coagulation and cause cerebral microembolism which could damage the brain. Methods and results: We cross-sectionally evaluated 122 stroke-free individuals with AF recruited locally within the German Competence Network on AF. As comparator, we recruited 563 individuals aged 37-84 years without AF from the same community. Subjects underwent 3 T magnetic resonance imaging to assess covert territorial brain infarction, white matter lesions, and brain volume measures. Subjects with evidence for stroke, dementia, or depression were excluded. Cognitive function was assessed by an extensive neuropsychological test battery covering the domains learning and memory, attention and executive functions, working memory, and visuospatial skills. Cognitive scores and radiographic measures were compared across individuals with and without AF by stepwise multiple regression models. Stroke-free individuals with AF performed significantly worse in tasks of learning and memory (ß = -0.115, P < 0.01) as well as attention and executive functions (ß = -0.105, P < 0.01) compared with subjects without AF. There was also a trend (P = 0.062) towards worse performance in learning and memory tasks in patients with chronic as compared with paroxysmal AF. Corresponding to the memory impairment, hippocampal volume was reduced in patients with AF. Other radiographic measures did not differ between groups. Conclusion: Even in the absence of manifest stroke, AF is a risk factor for cognitive impairment and hippocampal atrophy. Therefore, cognition and measures of structural brain integrity should be considered in the evaluation of novel treatments for AF. © The Author 2008.",,"Knecht, S.;Oelschläger, C.;Duning, T.;Lohmann, H.;Albers, J.;Stehling, C.;Heindel, W.;Breithardt, G.;Berger, K.;Ringelstein, E. B.;Kirchhof, P.;Wersching, H.",2008,September,,0,
3279,Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B,"This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/metabolism/physiopathology/ radionuclide imaging;Amyloid/ metabolism;Aniline Compounds/blood/chemistry;Autoradiography/methods;Binding Sites;Brain/anatomy & histology/ metabolism;Brain Chemistry;Diagnosis, Differential;Female;Fluorodeoxyglucose F18;Glucose/metabolism;Humans;Male;Middle Aged;Thiazoles/blood/chemistry;Time Factors;Tomography, Emission-Computed/ methods","Klunk, W. E.;Engler, H.;Nordberg, A.;Wang, Y.;Blomqvist, G.;Holt, D. P.;Bergstrom, M.;Savitcheva, I.;Huang, G. F.;Estrada, S.;Ausen, B.;Debnath, M. L.;Barletta, J.;Price, J. C.;Sandell, J.;Lopresti, B. J.;Wall, A.;Koivisto, P.;Antoni, G.;Mathis, C. A.;Langstrom, B.",2004,Mar,10.1002/ana.20009,0,
3280,Applying Automated MR-Based Diagnostic Methods to the Memory Clinic: A Prospective Study,"Several studies have demonstrated that fully automated pattern recognition methods applied to structural magnetic resonance imaging (MRI) aid in the diagnosis of dementia, but these conclusions are based on highly preselected samples that significantly differ from that seen in a dementia clinic. At a single dementia clinic, we evaluated the ability of a linear support vector machine trained with completely unrelated data to differentiate between Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia, and healthy aging based on 3D-T1 weighted MRI data sets. Furthermore, we predicted progression to AD in subjects with mild cognitive impairment (MCI) at baseline and automatically quantified white matter hyperintensities from FLAIR-images. Separating additionally recruited healthy elderly from those with dementia was accurate with an area under the curve (AUC) of 0.97 (according to Fig. 4). Multi-class separation of patients with either AD or FTD from other included groups was good on the training set (AUC > 0.9) but substantially less accurate (AUC = 0.76 for AD, AUC = 0.78 for FTD) on 134 cases from the local clinic. Longitudinal data from 28 cases with MCI at baseline and appropriate follow-up data were available. The computer tool discriminated progressive from stable MCI with AUC = 0.73, compared to AUC = 0.80 for the training set. A relatively low accuracy by clinicians (AUC = 0.81) illustrates the difficulties of predicting conversion in this heterogeneous cohort. This first application of a MRI-based pattern recognition method to a routine sample demonstrates feasibility, but also illustrates that automated multi-class differential diagnoses have to be the focus of future methodological developments and application studies.",,"Kloppel, S.;Peter, J.;Ludl, A.;Pilatus, A.;Maier, S.;Mader, I.;Heimbach, B.;Frings, L.;Egger, K.;Dukart, J.;Schroeter, M. L.;Perneczky, R.;Haussermann, P.;Vach, W.;Urbach, H.;Teipel, S.;Hull, M.;Abdulkadir, A.",2015,,10.3233/jad-150334,0,
3281,MRI-based diagnostics of dementia,"Structural magnetic resonance imaging (MRI) is gaining relevance for the diagnosis of dementia syndromes. It helps to identify potentially curable causes but also provides positive predictive value to the diagnosis of specific types of dementia. T1-weighted sequences aid in the assessment of atrophy while FLAIR and T2*-weighing provides information on white matter hyperintensities and microbleeds. In context of clinical studies of Alzheimer's Disease (AD), MRI has proven to be a valuable marker of disease progression. MRI is highly correlated with the underlying pathophysiology of",,"Klöppel, S.;Mader, I.",2013,2013,,0,
3282,White matter connections reflect changes in voluntary-guided saccades in pre-symptomatic Huntington's disease,"Huntington's disease is caused by a known genetic mutation and so potentially can be diagnosed many years before the onset of symptoms. Neuropathological changes have been found in both striatum and frontal cortex in the pre-symptomatic stage. Disruption of cortico-striatal white matter fibre tracts is therefore likely to contribute to the first clinical signs of the disease. We analysed diffusion tensor MR image (DTI) data from 25 pre-symptomatic gene carriers (PSCs) and 20 matched controls using a multivariate support vector machine to identify patterns of changes in fractional anisotropy (FA). In addition, we performed probabilistic fibre tracking to detect changes in 'streamlines' connecting frontal cortex to striatum. We found a pattern of structural brain changes that includes putamen bilaterally as well as anterior parts of the corpus callosum. This pattern was sufficiently specific to enable us to correctly classify 82% of scans as coming from a PSC or control subject. Fibre tracking revealed a reduction of frontal cortico-fugal streamlines reaching the body of the caudate in PSCs compared to controls. In the left hemispheres of PSCs we found a negative correlation between years to estimated disease onset and streamlines from frontal cortex to body of caudate. A large proportion of the fibres to the caudate body originate from the frontal eye fields, which play an important role in the control of voluntary saccades. This type of saccade is specifically impaired in PSCs and is an early clinical sign of motor abnormalities. A correlation analysis in 14 PSCs revealed that subjects with greater impairment of voluntary-guided saccades had fewer fibre tracking streamlines connecting the frontal cortex and caudate body. Our findings suggest a specific patho-physiological basis for these symptoms by indicating selective vulnerability of the associated white matter tracts.",Adult;Anisotropy;Brain/ pathology;Brain Mapping/methods;Corpus Striatum/pathology;Diffusion Magnetic Resonance Imaging/methods;Female;Frontal Lobe/pathology;Heterozygote;Humans;Huntington Disease/genetics/ pathology/ physiopathology;Male;Middle Aged;Nerve Fibers/pathology;Neural Pathways/pathology;Saccades,"Kloppel, S.;Draganski, B.;Golding, C. V.;Chu, C.;Nagy, Z.;Cook, P. A.;Hicks, S. L.;Kennard, C.;Alexander, D. C.;Parker, G. J.;Tabrizi, S. J.;Frackowiak, R. S.",2008,Jan,10.1093/brain/awm275,0,
3283,A comparison of different automated methods for the detection of white matter lesions in MRI data,"White matter hyperintensities (WMH) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMH labour intensive and prone to subjective bias.This study compares fully automated supervised detection methods that learn to identify WMH from manual examples against unsupervised approaches on the combination of FLAIR and T1 weighted images. Data were collected from ten subjects with mild cognitive impairment and another set of ten individuals who fulfilled diagnostic criteria for dementia. Data were split into balanced groups to create a training set used to optimize the different methods. Manual outlining served as gold standard to evaluate performance of the automated methods that identified each voxel either as intact or as part of a WMH.Otsu's approach for multiple thresholds which is based only on voxel intensities of the FLAIR image produced a high number of false positives at grey matter boundaries. Performance on an independent test set was similarly disappointing when simply applying a threshold to the FLAIR that was found from training data. Among the supervised methods, precision-recall curves of support vector machines (SVM) indicated advantages over the performance achieved by K-nearest-neighbor classifiers (KNN). The curves indicated a clear benefit from optimizing the threshold of the SVM decision value and the voting rule of the KNN. Best performance was reached by selecting training voxels according to their distance to the lesion boundary and repeated training after replacing the feature vectors from those voxels that did not form support vectors of the SVM.The study demonstrates advantages of SVM for the problem of detecting WMH at least for studies that include only FLAIR and T1 weighted images. Various optimization strategies are discussed and compared against each other. © 2011 Elsevier Inc.",,"Klöppel, S.;Abdulkadir, A.;Hadjidemetriou, S.;Issleib, S.;Frings, L.;Thanh, T. N.;Mader, I.;Teipel, S. J.;Hüll, M.;Ronneberger, O.",2011,15,,0,
3284,Longitudinal Assessment of Amyloid Pathology in Transgenic ArcAbeta Mice Using Multi-Parametric Magnetic Resonance Imaging,"Magnetic resonance imaging (MRI) can be used to monitor pathological changes in Alzheimer's disease (AD). The objective of this longitudinal study was to assess the effects of progressive amyloid-related pathology on multiple MRI parameters in transgenic arcAbeta mice, a mouse model of cerebral amyloidosis. Diffusion-weighted imaging (DWI), T1-mapping and quantitative susceptibility mapping (QSM), a novel MRI based technique, were applied to monitor structural alterations and changes in tissue composition imposed by the pathology over time. Vascular function and integrity was studied by assessing blood-brain barrier integrity with dynamic contrast-enhanced MRI and cerebral microbleed (CMB) load with susceptibility weighted imaging and QSM. A linear mixed effects model was built for each MRI parameter to incorporate effects within and between groups (i.e. genotype) and to account for changes unrelated to the disease pathology. Linear mixed effects modelling revealed a strong association of all investigated MRI parameters with age. DWI and QSM in addition revealed differences between arcAbeta and wt mice over time. CMBs became apparent in arcAbeta mice with 9 month of age; and the CMB load reflected disease stage. This study demonstrates the benefits of linear mixed effects modelling of longitudinal imaging data. Moreover, the diagnostic utility of QSM and assessment of CMB load should be exploited further in studies of AD.",,"Klohs, J.;Politano, I. W.;Deistung, A.;Grandjean, J.;Drewek, A.;Dominietto, M.;Keist, R.;Schweser, F.;Reichenbach, J. R.;Nitsch, R. M.;Knuesel, I.;Rudin, M.",2013,,10.1371/journal.pone.0066097,0,
3285,Detection of cerebral microbleeds with quantitative susceptibility mapping in the ArcAbeta mouse model of cerebral amyloidosis,"Cerebral microbleeds (CMBs) are findings in patients with neurological disorders such as cerebral amyloid angiopathy and Alzheimer's disease, and are indicative of an underlying vascular pathology. A diagnosis of CMBs requires an imaging method that is capable of detecting iron-containing lesions with high sensitivity and spatial accuracy in the presence of potentially confounding tissue abnormalities. In this study, we investigated the feasibility of quantitative magnetic susceptibility mapping (QSM), a novel technique based on gradient-recalled echo (GRE) phase data, for the detection of CMBs in the arcAbeta mouse, a mouse model of cerebral amyloidosis. Quantitative susceptibility maps were generated from phase data acquired with a high-resolution T(2)(*)-weighted GRE sequence at 9.4 T. We examined the influence of different regularization parameters on susceptibility computation; a proper adjustment of the regularization parameter minimizes streaking artifacts and preserves fine structures. In the present study, it is shown that QSM provides increased detection sensitivity of CMBs and improved contrast when compared with GRE magnitude imaging. Furthermore, QSM corrects for the blooming effect observed in magnitude and phase images and depicts both the localization and spatial extent of CMBs with high accuracy. Therefore, QSM may become an important tool for diagnosing CMBs in neurological diseases.","Algorithms;Amyloid/ genetics;Anatomy, Cross-Sectional;Animals;Brain Mapping;Cerebral Amyloid Angiopathy/complications/ genetics/pathology;Cerebral Hemorrhage/etiology/ genetics/pathology;Data Interpretation, Statistical;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Magnetic Resonance Imaging;Mice;Mice, Inbred C57BL;Mice, Transgenic","Klohs, J.;Deistung, A.;Schweser, F.;Grandjean, J.;Dominietto, M.;Waschkies, C.;Nitsch, R. M.;Knuesel, I.;Reichenbach, J. R.;Rudin, M.",2011,Dec,10.1038/jcbfm.2011.118,0,
3286,The epsilon4 genotype of apolipoprotein E and white matter integrity in Alzheimer's disease,"BACKGROUND: In this multicenter study, we investigated a possible association between the APOE epsilon4 allele and white matter (WM) integrity in Alzheimer's disease (AD) using diffusion tensor imaging (DTI). METHODS: We analyzed fractional anisotropy (FA) and mean diffusivity (MD) as indices of WM integrity in 70 AD patients (35 APOE epsilon4 carriers, 35 noncarriers) and 56 healthy control (HC) subjects (28 APOE epsilon4 carriers, 28 noncarriers). APOE epsilon4 carriers and noncarriers were matched for age and gender within each diagnostic group. RESULTS: We found significant effects of diagnosis (Pcorrected < .05 [FWE]; i.e., smaller FA values and larger MD values in AD patients compared with HCs) and significant effects (P < .001) of APOE epsilon4 carrier status on MD in HCs but not in AD subjects. CONCLUSIONS: The results indicate that APOE epsilon4 has a moderate effect on WM integrity in HCs, but no effect on WM integrity in manifest AD.","Aged;Aged, 80 and over;Alzheimer Disease/ genetics/ pathology;Anisotropy;Apolipoprotein E4/ genetics;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Genotype;Heterozygote;Humans;Male;Middle Aged;White Matter/ pathology","Kljajevic, V.;Meyer, P.;Holzmann, C.;Dyrba, M.;Kasper, E.;Bokde, A. L.;Fellgiebel, A.;Meindl, T.;Hampel, H.;Teipel, S.",2014,May,10.1016/j.jalz.2013.02.008,0,
3287,Is the left uncinate fasciculus associated with verbal fluency decline in mild Alzheimer's disease?,"The association between verbal fluency deficit in Alzheimer's disease (AD) and deterioration of specific white matter (WM) tracts is currently not well understood. Using diffusion tensor imaging, we investigated a possible association between the left uncinate fasciculus, which has been implicated in word retrieval, and verbal fluency deficit in AD. A comparison of five properties of WM (fractional anisotropy, mode of anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) in 28 mild AD patients and 26 age-, gender- and education-matched healthy controls revealed significant group differences in a range of WM tracts. Looking specifically at diffusion parameters' values for the left uncinate fasciculus and verbal fluency scores in the AD group, we observed a positive trend between the letter fluency scores and mode of anisotropy values (r = 0.36, p = 0.55). Thus, our data suggest more global WM damage in mild AD, which also includes damage to the left uncinate fasciculus. However, damage to this particular tract is not robustly associated with verbal fluency decline at this stage of disease.",Diffusion tensor imaging (DTI);Uncinate fasciculus;Verbal fluency;White matter;mild Alzheimer's disease,"Kljajevic, V.;Dyrba, M.;Kasper, E.;Teipel, S.",2016,,,0,
3288,Cognitive state following stroke: The predominant role of preexisting white matter lesions,"Background and purpose: Stroke is a major cause of cognitive impairment and dementia in adults, however the role of the ischemic lesions themselves, on top of other risk factors known in the elderly, remains controversial. This study used structural equation modeling to determine the respective impact of the new ischemic lesions' volume, preexisting white matter lesions and white matter integrity on post stroke cognitive state. Methods: Consecutive first ever mild to moderate stroke or transient ischemic attack patients recruited into the ongoing prospective TABASCO study underwent magnetic resonance imaging scans within seven days of stroke onset and were cognitively assessed one year after the event using a computerized neuropsychological battery. The volumes of both ischemic lesions and preexisting white matter lesions and the integrity of the normal appearing white matter tissue were measured and their contribution to cognitive state was assessed using structural equation modeling path analysis taking into account demographic parameters. Two models were hypothesized, differing by the role of ischemic lesions' volume. Results: Structural equation modeling analysis of 142 patients confirmed the predominant role of white matter lesion volume (standardized path coefficient β = -0.231) and normal appearing white matter integrity (β = -0.176) on the global cognitive score, while ischemic lesions' volume showed no such effect (β = 0.038). The model excluding the ischemic lesion presented better fit to the data (comparative fit index 0.9 versus 0.092). Conclusions: Mild to moderate stroke patients with preexisting white matter lesions are more vulnerable to cognitive impairment regardless of their new ischemic lesions. Thus, these patients can serve as a target group for studies on cognitive rehabilitation and neuro-protective therapies which may, in turn, slow their cognitive deterioration. © 2014 Kliper et al.",,"Kliper, E.;Ben Assayag, E.;Tarrasch, R.;Artzi, M.;Korczyn, A. D.;Shenhar-Tsarfaty, S.;Aizenstein, O.;Hallevi, H.;Mike, A.;Shopin, L.;Bornstein, N. M.;Ben Bashat, D.",2014,,,0,
3289,Elevated cerebellar glucose metabolism in microvascular white matter disease: normal aging and Alzheimer's disease,"Young normal, elderly, and clinically diagnosed Alzheimer disease subjects who had undergone positron emission tomography (PET) and computed tomography (CT) examinations were studied to determine the effect of periventricular white matter lesions on cerebellar glucose metabolic rates. PET-determined cerebellar metabolic rates were elevated in subjects with periventricular white matter lesions. These results suggest the cautious use of cortical-to-cerebellar ratios in future PET or single-photon-emission CT (SPECT) studies.","Adult;Aged;Aged, 80 and over;Aging/*metabolism;Alzheimer Disease/*metabolism/radionuclide imaging;Analysis of Variance;Cerebellum/*metabolism/radionuclide imaging;Cerebral Ventricles/radionuclide imaging;Glucose/*metabolism;Humans;Middle Aged;Tomography, Emission-Computed","Klinger, A.;de Leon, M. J.;George, A. E.;Miller, J. D.;Wolf, A. P.",1988,Jun,10.1038/jcbfm.1988.80,0,
3290,Factors associated with pre-stroke dementia: the cracow stroke database,"BACKGROUND: Many stroke patients who fulfilled diagnostic criteria for dementia three months after stroke had a mental deterioration before stroke, implying an underlying neurodegenerative process. The goal of this study was to determine the factors associated with pre-stroke dementia in hospitalised-based population. SUBJECTS AND METHODS: Pre-stroke cognitive decline was evaluated in 250 stroke patients using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients with IQCODE score > or=104 were classified as having pre-stroke dementia. Clinical, radiological, and biochemical data of patients with and without pre-stroke dementia were compared. RESULTS: Pre-stroke dementia was found in 12% of 250 stroke patients. Patients with pre-stroke dementia were older, suffered more frequently from ischemic heart disease and diabetes, and had more frequently prior cerebrovascular disease. These patients had significantly more brain atrophy and number of old infarcts on CT than patients without pre-stroke dementia. Serum gamma-globulins levels at admission were significantly higher in patients with pre-stroke dementia. In logistic regression analysis female gender (OR 3.47, CI 95% 1.25-9.64), history of previous stroke (OR 3.46, CI 95 % 1.26-9.51), the number of old infarcts on CT (OR 1.58, CI 95 % 1.08-2.33) and serum gamma-globulins level (OR 1.19, CI 95 % 1.02-1.40) were independently associated with pre-stroke dementia. CONCLUSIONS: Female gender and previous ischemic stroke are the most important determinants of pre-stroke cognitive decline.","Aged;Aged, 80 and over;Cerebrovascular Disorders/*complications/epidemiology/physiopathology;Cognition Disorders/*etiology;Dementia/*complications/epidemiology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Risk Factors;Surveys and Questionnaires","Klimkowicz, A.;Dziedzic, T.;Polczyk, R.;Pera, J.;Slowik, A.;Szczudlik, A.",2004,May,10.1007/s00415-004-0384-5,0,
3291,"Central nervous system angiocentric, angiodestructive T-cell lymphoma (lymphomatoid granulomatosis)","Most neurosurgeons and neurologists still consider lymphomatoid granulomatosis (LG) as a type of central nervous system (CNS) vasculitis. However, new insights, primarily from the hematologic literature, have cast doubt on the benign character of this disorder. In this article we (1) report a case of an 18-year-old woman with diffuse CNS disease and no mass lesion who developed multiple small cortical infarcts and dementia secondary to multifocal angiocentric, angiodestructive lymphoma; we (2) review other cases of LG with predominant CNS involvement; we (3) summarize the current understanding of LG, which is now considered to be a premalignant or overt angiocentric, angiodestructive T-cell lymphoma rather than a non-neoplastic vasculitis: the importance to neurologic surgeons and neurologists is that while pulmonary involvement in LG is generally the most prominent finding, patients may present with early or dramatic CNS disease; and we (4) note that although dementia is uncommon in young adults, this report adds yet another rare condition to the long differential list of dementia in this age group.",prednisone;adult;article;case report;dementia;female;human;human tissue;immunohistochemistry;lymphoma;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;T lymphocyte,"Kleinschmidt-DeMasters, B. K.;Filley, C. M.;Bitter, M. A.",1992,,,0,
3292,The imaging and neuropathological effects of Bevacizumab (Avastin) in patients with leptomeningeal carcinomatosis,"Bevacizumab (Avastin, Genetech/Roche) is an anti-angiogenic drug approved for treating patients with malignant gliomas that reduces edema and mass effect, but has been suggested to promote multifocal tumor spread within the brain. Patients with systemic malignancies are also treated with bevacizumab, but there is limited information regarding effects of the drug on the neuroimaging or neuropathological features of metastatic CNS disease. We report 2 patients with non-small cell lung carcinomas who had received bevacizumab for their systemic cancers and then developed cognitive deficits consistent with white matter dementia. Diagnosis of leptomeningeal carcinomatosis (LC) was confounded and delayed by the finding of atypical neuroimaging features, including minimal to absent leptomeningeal enhancement and unusual perivascular and punctate hemorrhagic lesions and multifocal subgyral signal abnormalities suspicious for vasculitis or small vessel vasculopathy. Neuropathological assessment confirmed LC but, in the autopsy case also disclosed extraordinary perivascular spread of individual metastatic tumor cells to the depth of capillaries. The pattern was reminiscent of vascular ""cooption"" by tumor seen in experimental animals in preclinical trials of bevacizumab. Small infarctions were associated with perivascular tumor and vasculopathy, unusual features of LC in patients who do not receive bevacizumab. In the biopsied patient, multiple perivascular tumor nodules were identified in superficial cortex. In these two patients, bevacizumab appeared to alter neuroimaging characteristics of LC, confounded diagnosis and possibly also influenced the pattern of tumor spread of LC. More cases will need to be studied to confirm this latter finding. © 2009 Springer Science+Business Media, LLC.",,"Kleinschmidt-Demasters, B. K.;Damek, D. M.",2010,February,,0,
3293,Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia: Report of five cases and a new mutation,"The objective of this work is to report on a series of five patients with adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP). ALSP is a rare adult-onset leukodystrophy, which encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmentary orthochromatic leukodystrophy. This was a retrospective chart review and literature review. Five previously healthy women presented with a rapidly progressive neurological disorder at ages 39, 37, 40, 30, and 47, respectively. All five individuals were initially diagnosed as suffering from multiple sclerosis. The clinical courses of the five patients were dominated by progressive spastic quadriparesis (patient 5, newly diagnosed, has paraparesis at this time) and dementia. Brain magnetic resonance imaging (MRI) showed diffuse cerebral atrophy, corpus callosal atrophy, and diffuse T2 hyperintensities in the subcortical and periventricular white matter with no gadolinium enhancing lesions. Three patients showed involvement of pyramidal tracts from motor cortex to the brainstem. Cerebrospinal fluid was normal in all cases. Diagnosis of ALSP was established by biopsy (two cases) and autopsy (two cases). Histopathology showed the presence of neuroaxonal spheroids in all four cases and pigmented glia in three. In the fifth case, diagnosis was established by genetic analysis alone that showed a disease-causing mutation in the colony-stimulating factor 1 receptor (CSF1R) gene. Genetic analysis was done in three patients with available DNA, and identified the disease-causing mutation in all three, including a novel mutation F828S. ALSP may be suspected in adults with rapid to subacute progression of neurological disease when (1) MRI shows corpus callosal atrophy on a background of generalized brain atrophy and diffuse white matter disease without postcontrast enhancement, (2) CSF studies are normal, and (3) studies for systemic inflammatory diseases and specific leukodystrophies are normal. Diagnosis may be made without histopathological evidence when a disease-causing mutation is demonstrated in the CSF1R gene. © 2012 Springer-Verlag Berlin Heidelberg.",,"Kleinfeld, K.;Mobley, B.;Hedera, P.;Wegner, A.;Sriram, S.;Pawate, S.",2013,February,,0,
3294,Proton chemical shift imaging in normal pressure hydrocephalus,"BACKGROUND AND PURPOSE: Differentiation of normal pressure hydrocephalus (NPH) from other types of dementia and the selection of appropriate candidates for shunt surgery remain a clinical challenge. The aims of this study were to assess the efficacy of cerebral metabolites depicted by proton chemical shift imaging ((1)H-CSI) in distinguishing NPH from other dementias and to examine the relationship between metabolite changes and the outcome of shunt surgery. METHODS: (1)H-CSI measurements were obtained in nine patients with clinical diagnosis of NPH; six patients with other types of dementia, including Alzheimer and Pick disease; and five control subjects. The (1)H-CSI sequence consisted of a double spin-echo sequence with imaging parameters of 2000/135/4-2 (TR/TE/acquisitions). Volumes of interest were selected from a section through the lateral ventricles. The peak areas and ratios of N-acetylaspartate, creatine, choline, and lactate were calculated. In two patients, follow-up (1)H-CSI and N-isopropyl ((123)I)-p-iodoamphetamine brain perfusion imaging were available after treatment with continuous spinal drainage. RESULTS: Lactate peaks were observed in the lateral ventricles for all patients with NPH (lactate/creatine, 0.23 ± 0.14) but not for patients with other types of dementia or control subjects. In all cases, we noted no significant differences in the peak ratios in the voxels located at the white matter near the lateral ventricles. In one patient with NPH, intraventricular lactate disappeared and regional CBF recovered after drainage. CONCLUSION: The intraventricular lactate level may be useful in differentiating NPH from other types of dementia.",,"Kizu, O.;Yamada, K.;Nishimura, T.",2001,2001,,0,
3295,"[Prevalence, incidence, and risk factors of vascular dementia: the Hisayama study]","We studied the type-specific prevalence, incidence, and risk factors of vascular dementia in elderly persons from a Japanese community of Hisayama. In 1985, we performed a screening survey of dementia among 887 Hisayama residents > or = 65 years or older (screening rate, 95%), using clinical information and Hasegawa's dementia scale, and consequently, determined 59 subjects as demented. Of these, 58 cases underwent brain examinations at autopsy and/or computed tomography during the subsequent 12.5 years. Among the 58 cases of dementia, the frequency of vascular dementia (VD) was 43%: the rate was 2 times higher than that for Alzheimer's disease (AD). In the subjects of VD, the most frequent type of stroke was due to small-artery disease, which caused multiple lacunar infarction (40%) and Binswanger's disease (12%). We also followed the 826 nondemented subjects for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general population. The age-adjusted total incidence (per 1,000 person-years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates of VD were 12.2 for men and 9.0 for women, and for AD 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology was examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant risk factors for the occurrence of VD.","Age Factors;Aged;Cohort Studies;Dementia, Vascular/*epidemiology;Female;Humans;Incidence;Japan/epidemiology;Male;Prevalence;Risk Factors;Sex Factors","Kiyohara, Y.",1999,Jan,,0,
3296,Hypertension and white matter lesions of the brain,,myelin;Alzheimer disease;atherosclerosis;autoregulation;cardiovascular disease;cognitive defect;gliosis;hypertension;nerve fiber;nuclear magnetic resonance imaging;priority journal;pulse pressure;rating scale;risk factor;short survey;white matter,"Kivipelto, M.;Soininen, H.;Tuomilehto, J.",2002,,,0,
3297,White matter changes in dementia with Lewy bodies and Alzheimer's disease: a tractography-based study,"Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are different types of dementia. However, their clinical symptoms partially overlap and differential diagnosis is occasionally difficult. There is need for additional diagnostic criteria to reliably differentiate between these two conditions. Meanwhile, several imaging studies have showed inconsistent results between DLB and AD. The aim of this study was to use a tractography-based analysis to elucidate white matter alterations in subjects with DLB compared to those with AD and to controls. An understanding of the white matter connectivity differences between AD, DLB and controls will be helpful for differential diagnosis and an understanding of the pathophysiology. Twenty-six subjects with DLB, 26 with AD and 26 controls underwent magnetic resonance diffusion tensor imaging and neuropsychological assessment. Diffusion tensors were computed and fiber-tract maps were created using ""dTV II"" software. We measured mean fractional anisotropy (FA) values along the uncinate fasciculus (UNC), the inferior occipitofrontal fasciculus (IOFF) and the inferior longitudinal fasciculus (ILF). Both subjects with DLB and AD had lower FA values for the bilateral UNC than controls. Subjects with DLB exhibited significantly lower FA values on both sides of the IOFF and the left side of the ILF than those of controls. Although there were no significant differences between subjects with DLB and AD for any measurements, those with DLB exhibited lower FA values especially in visual-related white matter. These different changes in white matter tracts among groups could be helpful for differential diagnosis and an understanding of the pathophysiology.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging/methods;Female;Humans;Lewy Body Disease/ pathology;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Reproducibility of Results;Statistics, Nonparametric","Kiuchi, K.;Morikawa, M.;Taoka, T.;Kitamura, S.;Nagashima, T.;Makinodan, M.;Nakagawa, K.;Fukusumi, M.;Ikeshita, K.;Inoue, M.;Kichikawa, K.;Kishimoto, T.",2011,Aug,10.1016/j.jpsychires.2011.01.011,0,
3298,"Gray and white matter changes in subjective cognitive impairment, amnestic mild cognitive impairment and Alzheimer's disease: a voxel-based analysis study","Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer's disease. The subjects in this study were 39 Alzheimer's disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer's disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer's disease.",Aged;Alzheimer Disease/complications/ pathology;Amnesia/complications/ pathology;Anisotropy;Atrophy;Demography;Female;Gray Matter/ pathology;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/complications/ pathology;White Matter/ pathology,"Kiuchi, K.;Kitamura, S.;Taoka, T.;Yasuno, F.;Tanimura, M.;Matsuoka, K.;Ikawa, D.;Toritsuka, M.;Hashimoto, K.;Makinodan, M.;Kosaka, J.;Morikawa, M.;Kichikawa, K.;Kishimoto, T.",2014,,10.1371/journal.pone.0104007,0,
3299,Cerebral hemodynamics in multiple cerebral infarction with or without dementia,"Cerebral blood flow and metabolism in 25 patients with multiple cerebral infarcts (14 with dementia) and 5 healthy age-matched controls were measured to investigate the difference in cerebral blood low (CBF) and cerebral oxygen consumption (CMRO2) between patients with dementia and patients without dementia. None of the patients had any lesions in the cortex, but all had multiple lesions in the basal ganglionic region, and in the white matter, according to CT images. CBF, CMRO2 and oxygen extraction fraction were measured by positron emission tomography (PET) using the 15O2, C15O2 steady state inhalational technique. In patients with multiple cerebral infarcts the absolute values of CBF and CMRO2 were decreased significantly from normal control values, and there was no significant difference in the absolute values of CBF and CMRO2 between patients with dementia and patients without dementia. In most patients with dementia, relative values (regional value/mean cortical value) of CBF and CMRO2 decreased in the frontal and the parietal cortex. Four patients had repeated PET studies. In two of them, decrease in CMRO2 was preceded by decrease in CBF. These results suggest that dysfunction of frontal cortex and parietal cortex, and chronic ischemia might be related to the occurrence of dementia in patients with multiple cerebral infarcts, which were in the basal ganglia and the white matter.","Aged;Brain/metabolism;Cerebral Infarction/metabolism/ physiopathology;Cerebrovascular Circulation;Dementia, Multi-Infarct/metabolism/ physiopathology;Female;Hemodynamics;Humans;Male;Middle Aged;Oxygen Consumption;Tomography, Emission-Computed","Kitamura, S.;Terashi, A.;Araki, T.;Sakamoto, S.;Ujike, T.;Soeda, T.;Iio, M.",1989,Nov,,0,
3300,Benzodiazepine receptor and cerebral blood flow in early Alzheimer's disease--SPECT study using 123I-iomazenil and 123I-IMP,"This study was designed to investigate benzodiazepine receptors (BZR) and cerebral blood flow (CBF) in patients with early Alzheimer's disease. Imaging of BZR and measurement of CBF were performed by SPECT using 123I-Iomazenil (IMZ) and 123I-IMP respectively, in seven patients with early Alzheimer's disease and five patients with unilateral left cerebral infarction as controls. The values for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with cerebral infarction were adopted as control values. In patients with Alzheimer's disease, the CBF (ratio to cerebellum) decreased significantly in the frontal cortex and the parietal cortex compared with the control values. There was no significant difference in late IMZ SPECT counts (ratio to cerebellum) and washout (the ratio of late-to-early IMZ SPECT counts) between patients with Alzheimer's disease and the controls. However, the late IMZ SPECT counts and washout decreased in one patient with moderate dementia. There was a significant correlation between the severity of dementia and the late IMZ SPECT counts in the temporal cortex and the parietal cortex. These results suggest that benzodiazepine binding sites are relatively well preserved in patients with early Alzheimer's disease, and reduction of the CBF is caused by neuronal dysfunction rather than by neuronal loss. IMZ SPECT study is useful and necessary for clarifying the pathophysiological state in Alzheimer's disease.","Aged;Alzheimer Disease/ physiopathology;Amphetamines;Brain/metabolism/ radionuclide imaging;Cerebrovascular Circulation;Female;Flumazenil/ analogs & derivatives;Humans;Iodine Radioisotopes;Iofetamine;Middle Aged;Receptors, GABA-A/metabolism;Tomography, Emission-Computed, Single-Photon","Kitamura, S.;Koshi, Y.;Komiyama, T.;Sakayori, O.;Komaba, Y.;Ohyama, M.;Mishina, M.;Tsuganesawa, T.;Terashi, A.",1996,Jan,,0,
3301,Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study,"Alzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ metabolism;Diffusion Tensor Imaging/ methods;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Middle Aged;Nerve Fibers, Myelinated/ metabolism/ pathology","Kitamura, S.;Kiuchi, K.;Taoka, T.;Hashimoto, K.;Ueda, S.;Yasuno, F.;Morikawa, M.;Kichikawa, K.;Kishimoto, T.",2013,Jun 17,10.1016/j.brainres.2013.03.052,0,
3302,"Lymphomatosis cerebri: Clinical characteristics, neuroimaging, and pathological findings","Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma. We present a case involving a 56-year-old immunocompetent woman who complained of rapid deterioration of her higher brain function over a 4-month period. Magnetic resonance imaging showed extensive white-matter lesions. During brain biopsy, a diffusely infiltrating lymphoma with distinctive immunohistochemical features was detected. Awareness of this unique presentation and early tissue diagnosis provide the best hope for instituting appropriate treatments. © 2011 The Japan Society of Brain Tumor Pathology.",,"Kitai, R.;Hashimoto, N.;Yamate, K.;Ikawa, M.;Yoneda, M.;Nakajima, T.;Arishima, H.;Takeuchi, H.;Sato, K.;Kikuta, K. I.",2012,January,,0,
3303,[Anticardiolipin antibody in cerebral infarction],"We investigated the anticardiolipin antibody (ACA) in a series of patients with cerebral infarction without systemic lupus erythematosus (SLA). Clinical and laboratory data were assessed from a series of 250 non-SLE patients with cerebral infarction who visited our clinic from 1988 to 1990. The concentration of anticardiolipin IgG antibody was measured by an enzyme-linked immunosorbent assay technique. An elevated ACA level was defined as one which was greater than 3 standard deviations above the mean level for normal controls. We examined the CT findings and risk factors for stroke such as hypertension, diabetes mellitus, hyperlipidemia and cardiac disease. Laboratory data such as the platelet count, the presence of lupus anticoagulant and a biologic false-positive test for syphilis were also investigated. Among the 250 patients with infarction, IgG ACA was detected in 22 (8.8%). There was no significant difference in incidence of ACA between the patients with cerebral thrombosis and those with cerebral embolism. On CT scan, multiple cerebral infarcts were noted in 18 of the 22 patients. As regards the location of the infarct, the cerebral cortex together with the basal ganglia was more common than isolated lesions of the cortex or basal ganglia. Concerning the risk factors for stroke, hypertension was noted in 12, diabetes mellitus in 2, hyperlipidemia in 2 and cardiac disease in 2. Lupus anticoagulant and thrombocytopenia were not detected in any of the cases. A biologic false-positive test for syphilis was observed in one case. Dementia was present in 12 of the 22 patients.(ABSTRACT TRUNCATED AT 250 WORDS)","Adult;Aged;Aged, 80 and over;Autoantibodies/*analysis;Cardiolipins/*immunology;Cerebral Infarction/etiology/*immunology;Female;Humans;Immunoglobulin G/*analysis;Male;Middle Aged;Risk Factors","Kitagawa, Y.;Okayasu, H.;Matsuoka, Y.;Mihara, B.;Koto, A.",1991,Apr,,0,
3304,Cerebral blood flow and brain atrophy correlated by xenon contrast CT scanning,"Correlations between cerebral blood flow (CBF) measured during stable xenon contrast CT scanning and standard CT indices of brain atrophy were investigated in the patients with senile dementia of Alzheimer type, multi-infarct dementia and idiopathic Parkinson's disease. Compared to age-matched normal volunteers, significant correlations were found in patients with idiopathic Parkinson's disease between cortical and subcortical gray matter blood flow and brain atrophy estimated by the ventricular body ratio, and mild to moderate brain atrophy were correlated with stepwise CBF reductions. However, in patients with senile dementia of Alzheimer type and multi-infarct dementia, brain atrophy was not associated with stepwise CBF reductions. Overall correlations between brain atrophy and reduced CBF were weak. Mild degrees of brain atrophy are not always associated with reduced CBF.","Aged;Alzheimer Disease/pathology/physiopathology/radiography;Atrophy;Brain/*pathology/radiography;Cerebral Ventricles/pathology;Cerebral Ventriculography/methods;*Cerebrovascular Circulation;Dementia/pathology/physiopathology/radiography;Female;Humans;Male;Middle Aged;Parkinson Disease/pathology/physiopathology/radiography;*Tomography, X-Ray Computed/methods;Xenon Radioisotopes","Kitagawa, Y.;Meyer, J. S.;Tanahashi, N.;Rogers, R. L.;Tachibana, H.;Kandula, P.;Dowell, R. E.;Mortel, K. F.",1985,Nov-Dec,,0,
3305,CT-CBF correlations of cognitive deficits in multi-infarct dementia,"Fifteen right-handed patients with Multi-Infarct Dementia underwent cognitive testing by the Jacobs Mini-Mental Scale (MMQ), and xenon contrast CT scanning. Local cerebral blood flow (LCBF) and local partition coefficient (L lambda) values were measured by stable xenon contrast CT scanning and potential methodological errors were discussed. Reduced values were graded: 0 = normal, 1 = mild, 2 = moderate, 3 = severe. Graded values were pooled and plotted on composite brain maps to display locations of abnormal L lambda and LCBF values. Topographic brain maps, showing most frequent locations of reduced L lambda values, confirmed the common anatomical locations of multiple cerebral infarcts to be distributed in both thalami, temporal lobes, basal ganglia, left internal capsule and right cingulate cortex. Gray matter flow values were reduced in similar cortical and subcortical regions. There were no correlations between MMQ scores and reduced LCBF values for caudate and lenticular nuclei. Direct and statistically significant correlations were found between reduced MMQ scores and mean LCBF values for left or right frontal cortex, left or right temporal cortex and left or right thalamus. Subgrouping MMQ tests according to functions assessed, indicated that left mid-temporal ischemia correlated with dyscalculia and memory disturbances while ischemia of both frontal lobes correlated with disorientation to time and place.","Aged;*Brain Mapping;Cerebral Infarction/complications/*radiography;*Cerebrovascular Circulation;Cognition Disorders/*diagnosis/etiology;Confusion/diagnosis;Dementia/*diagnosis/radiography;Female;Frontal Lobe/blood supply;Humans;Male;Memory Disorders/diagnosis;Middle Aged;Psychiatric Status Rating Scales;Temporal Lobe/blood supply;*Tomography, X-Ray Computed/methods","Kitagawa, Y.;Meyer, J. S.;Tachibana, H.;Mortel, K. F.;Rogers, R. L.",1984,Nov-Dec,,0,
3306,Creutzfeldt-Jakob disease: A case with extensive white matter degeneration and optic atrophy,"A 52-year-old woman is described, whose clinical features were typical of Creutzfeldt-Jakob disease except for the presence of optic atrophy. Serial CT scans showed rapid development of brain atrophy early in the course. Postmortem examination revealed extensive degeneration of the cerebral and cerebellar white matter and of the optic nerves in addition to the classic findings of Creutzfeldt-Jakob disease. It is suggested that both the grey and white matter may undergo a severe destructive process early in the course of the disease, and the possibility is discussed that the white matter involvement is not a result of neuronal loss.",adult;case report;central nervous system;Creutzfeldt Jakob disease;human;leukoencephalopathy;optic nerve atrophy;peripheral nervous system;visual system,"Kitagawa, Y.;Gotoh, F.;Koto, A.",1983,,,0,
3307,Relationship between cerebral blood flow and later cognitive decline in hypertensive patients with cerebral small vessel disease,"Vascular risk factors are thought to be important for dementia. However, there is little evidence for a prospective association between cerebral blood flow and the risk of cognitive decline. Twenty-seven cognitively intact hypertensive patients aged 55 years and older with lacunar infarction or white matter lesions in magnetic resonance imaging (MRI) underwent positron emission tomography (PET) to measure cerebral blood flow (CBF) and cerebral vascular reactivity (CVR). Cognitive function was assessed at baseline and 3 years later with the mini-mental state examination (MMSE). Patients whose MMSE score fell by more than three points were classified as having cognitive decline. Six patients showed cognitive decline. Baseline CBF in these patients was significantly lower than that of the 21 patients without cognitive decline (31.2+/-2.4 vs. 42.6+/-5.9 ml per 100 g min(-1), respectively; P<0.001). A moderate linear association was found between CBF and change in MMSE score over a 3-year period (r=0.59, P=0.001), not between CBF and baseline MMSE score. In contrast, no association between CVR and later cognitive decline was found. This study suggests that cerebral hypoperfusion is associated with later cognitive decline.",Aged;Atherosclerosis/complications/psychology;Cerebral Infarction/pathology/physiopathology;Cerebrovascular Circulation/ physiology;Cerebrovascular Disorders/ complications/pathology/radionuclide imaging;Cognition Disorders/ etiology/psychology;Dementia/etiology/psychology;Diabetes Mellitus/pathology;Female;Humans;Hypertension/ complications/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Positron-Emission Tomography;Risk Factors,"Kitagawa, K.;Oku, N.;Kimura, Y.;Yagita, Y.;Sakaguchi, M.;Hatazawa, J.;Sakoda, S.",2009,Sep,10.1038/hr.2009.100,0,
3308,Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors,"BACKGROUND AND PURPOSE: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined. METHODS: The Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients (n = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively. RESULTS: Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the follow-up period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log-rank test, P = 0.037 and P < 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22-6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex (P = 0.477). CONCLUSIONS: This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD.","Aged;Aged, 80 and over;Carotid Stenosis/diagnostic imaging/ epidemiology;Comorbidity;Dementia/diagnosis/ epidemiology;Female;Follow-Up Studies;Humans;Japan/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Stroke, Lacunar/diagnostic imaging/ epidemiology;Ultrasonography;carotid stenosis;dementia;lacunar infarction;vascular factor","Kitagawa, K.;Miwa, K.;Yagita, Y.;Okazaki, S.;Sakaguchi, M.;Mochizuki, H.",2015,Jan,,0,3309
3309,Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors,"Background and purpose: The association between vascular risk factors and dementia is of interest. Several studies have shown that cerebral small vessel disease (SVD) is associated with dementia. However, the association between cerebral large vessel disease (LVD) and dementia has not been thoroughly examined. Methods: The Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, was a prospective cohort study of cardiovascular events and dementia in which patients (n = 1106) with vascular risk factors underwent carotid ultrasound. Of these patients, 600 who had normal cognitive function were included and underwent brain magnetic resonance imaging. The presence of lacunar infarction and carotid stenosis served as markers for SVD and LVD, respectively. Results: Amongst 600 patients (mean 68 years, 57% men), 261 (44%) showed lacunar infarction and 94 (16%) showed carotid stenosis. During the follow-up period (median 8.0 years), 57 patients had incident dementia. Patients with carotid stenosis and lacunar infarction were significantly more likely to be diagnosed with dementia (log-rank test, P = 0.037 and P < 0.001, respectively). The association between lacunar infarction and dementia remained significant after adjusting for risk factors including stroke history, apolipoprotein E genotype and years of education (hazard ratio 2.64, 95% confidence interval 1.22-6.09). However, the presence of carotid stenosis was not associated with incident dementia after adjusting for age and sex (P = 0.477). Conclusions: This study demonstrated that carotid stenosis had little association with dementia, but lacunar infarction had a significant association. The impact of SVD on dementia could be much greater than that of LVD. © 2014 EAN.",,"Kitagawa, K.;Miwa, K.;Yagita, Y.;Okazaki, S.;Sakaguchi, M.;Mochizuki, H.",2014,,,0,
3310,Alteration of white matter MR signal intensity in frontotemporal dementia,PURPOSE: To determine the diagnostic potential of MR imaging to show white matter involvement in frontotemporal dementia. METHODS: We evaluated MR signal intensity in cerebral white matter by visually inspecting and by quantitatively measuring signal intensity on MR images in 22 patients with frontotemporal dementia. The findings were compared with those in 22 age- and sex-matched patients who had had Alzheimer disease for the same length of time and with 16 age- and sex-matched healthy control subjects. RESULTS: Patients with frontotemporal dementia had a significant increase in white matter signal intensity in the frontal and/or temporal lobes on T2- and proton density-weighted images. Visual inspection of regular proton density-weighted images and measurements made on the T2- and proton density-weighted images were sensitive to changes in white matter signal. CONCLUSION: Increased MR signal intensity in the frontotemporal white matter on T2- and proton density-weighted MR images is a useful diagnostic sign of frontotemporal dementia and distinguishes this condition from Alzheimer disease.,"Aged;Alzheimer Disease/diagnosis/pathology;Atrophy;Dementia/diagnosis/ pathology;Diagnosis, Differential;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Sensitivity and Specificity;Temporal Lobe/ pathology","Kitagaki, H.;Mori, E.;Hirono, N.;Ikejiri, Y.;Ishii, K.;Imamura, T.;Ikeda, M.;Yamaji, S.;Yamashita, H.;Shimomura, T.;Nakagawa, Y.",1997,Feb,,0,
3311,Two clinical cases diagnosed provisionally as Binswanger type of vascular dementia. On possibility of its clinical recognition from neuropsychiatric findings and computed tomography,"The diagnosis of subcortical arteriosclerotic encephalopathy of Binswanger should be confirmed neuropathologically by postmortem examination. But we expect that it may be possible to diagnose it provisionally as Binswanger's disease on the basis of clinical course and findings, including computed tomography. Two cases, a 57 yrs old postman (case 1) and a 60 yrs old housewife (case 2) were reported. They had hypertension for over 20 years in their past history, and showed a progressive dementia since before one year and 9 years. Transient syncopal attack and epileptiform seizure were revealed occasionally. Psychiatrically, both of them were apathic, aspontaneous and autistic. One of them (case 2) showed a striking paranoid-hallucinatory state. Spastic gait disturbance and dysarthria were found neurologically, and moreover in case 1, revealed the incontinence of urine and feces. Arteriosclerotic changes were seen in the fundi. The EEG showed a slow α rhythm with scattered θ- and δ-waves. Laboratory data of blood, urine and CSF were normal. On the basis of these clinical course and findings, the diagnosis of Binswanger's type of cerebral arteriosclerosis were suspected. The CT-scan of the 2 cases proved a symmetrical enlargement of the lateral ventricles and marginated areas of definite abnormal low density in the white matter of the occipital (case 1) and frontal (case 1 and 2) lobes. Conclusively, we may provisionally diagnose our two cases as Binswanger's disease, which is also supported by the findings of CT.",Binswanger encephalopathy;brain atherosclerosis;cardiovascular system;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;hypertension;peripheral vascular system;seizure,"Kita, H.;Uwadaira, C.;Harada, K.",1981,,,0,
3312,"Depressive symptoms, symptom dimensions, and white matter lesion volume in older adults: a longitudinal study","OBJECTIVE: White matter lesions (WMLs) are associated with depressive symptoms in older adults. However, it is not clear whether different symptom dimensions of depression have distinct associations with WMLs. The authors assessed the longitudinal relationships of the Center for Epidemiologic Studies Depression Scale (CES-D) total score and subscale scores with WML volume in the Baltimore Longitudinal Study of Aging. METHODS: Using a prospective observational design, the authors examined WML volume and depressive symptoms at 1- to 2-year intervals for up to 9 years in 116 dementia-free participants (mean age: 68.78 +/- 7.68). At each visit, depressive symptoms were measured with the CES-D and WML volumes were quantified from structural magnetic resonance imaging scans. RESULTS: Higher CES-D full-scale scores were associated with greater WML volume and with a faster rate of volume increases over time in women, especially at older ages. Higher depressed mood and somatic symptoms subscale scores were associated with greater increases in WML volume over time at older ages. In men, depressed mood and somatic symptoms were associated with larger WML volume at baseline. CONCLUSION: Findings confirm an association between WMLs and depressive symptoms and suggest that depressed mood and somatic symptoms may be stronger predictors of depression-related brain changes than lack of well-being. Age and sex may moderate the relationships between depressive symptoms and WMLs. Understanding particular symptom dimensions of depressive symptoms has implications for treatment and may lead to targeted interventions and more precise knowledge of mechanisms underlying depression.",Aged;Aging/ pathology;Depression/ physiopathology;Female;Humans;Leukoencephalopathies/ pathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged,"Kirton, J. W.;Resnick, S. M.;Davatzikos, C.;Kraut, M. A.;Dotson, V. M.",2014,Dec,10.1016/j.jagp.2013.10.005,0,
3313,"The Inflammatory Form of Cerebral Amyloid Angiopathy or ""Cerebral Amyloid Angiopathy-Related Inflammation"" (CAARI)","Cerebral amyloid angiopathy-related inflammation (CAARI) is a recently recognized syndrome of reversible encephalopathy seen in a subset of patients with cerebral amyloid angiopathy (CAA). CAA is a disorder of the elderly in which amyloid peptides are deposited in the walls of cerebral arteries, leading to microhemorrhages, macrohemorrhages, and eventually dementia. In a few cases, the amyloid deposition is accompanied by inflammation or edema. The clinical syndrome of CAARI is distinguished by subacute neurobehavioral symptoms, headaches, seizures, and stroke-like signs, contrasting the acute intracranial hemorrhage typically seen in CAA. Magnetic resonance imaging findings may be symmetric or asymmetric and involve patchy or confluent T2 hyperintense lesions in the cortex and subcortical white matter. Recent diagnostic criteria have been proposed which help distinguish CAARI from alternative diagnoses. Improvement has been reported in most cases with immunosuppression, although a few cases have had recurrent symptoms. Here, we review the clinical and radiologic features of CAARI and compare these with CAA.",,"Kirshner, H. S.;Bradshaw, M.",2015,Aug,10.1007/s11910-015-0572-y,0,
3314,Serial susceptibility weighted MRI measures brain iron and microbleeds in dementia,"A new iron sensitive MR sequence (susceptibility weighted imaging - SWI) enabling the simultaneous quantitation of regional brain iron levels and brain microbleeds (BMB) has been acquired serially to study dementia. Cohorts of mildly cognitively impaired (MCI) elderly (n = 73) and cognitively normal participants (n = 33) have been serially evaluated for up to 50 months. SWI phase values (putative iron levels) in 14 brain regions were measured and the number of BMB were counted for each SWI study. SWI phase values showed a left putaminal mean increase of iron (decrease of phase values) over the study duration in 27 participants who progressed to dementia compared to Normals (p = 0.035) and stable MCI (p = 0.01). BMB were detected in 9 out of 26 (38%) MCI participants who progressed to dementia and are a significant risk factor for cognitive failure in MCI participants [risk ratio = 2.06 (95% confidence interval 1.37-3.12)]. SWI is useful to measure regional iron changes and presence of BMB, both of which may be important MR-based biomarkers for neurodegenerative diseases. © 2009 - IOS Press and the authors. All rights reserved.",,"Kirsch, W.;McAuley, G.;Holshouser, B.;Petersen, F.;Ayaz, M.;Vinters, H. V.;Dickson, C.;Haacke, E. M.;Britt Iii, W.;Larsen, J.;Kim, I.;Mueller, C.;Schrag, M.;Kido, D.",2009,2009,,0,
3315,Prolongation of magnetic resonance T2 time in hippocampus of human patients marks the presence and severity of Alzheimer's disease,"Spin-spin relaxation time (T2) was measured in the hippocampal formation, thalamus, and cortical white matter in 13 patients with probable Alzheimer's disease (AD), 11 elderly normal individuals, 23 healthy young persons, and 9 subjects diagnosed with multi-infarct dementia. A 0.04 tesla magnetic resonance scanner was used. Hippocampal T2 values for all AD patients exceeded those of any non-AD individual, regardless of age or dementia due to infarction. Further, these T2 values were highly correlated (+0.96) with the severity of functional and cognitive impairment of the AD patients. This T2 prolongation was not observed at the other sites examined. These results suggest that hippocampal T2 prolongation may provide a specific marker by which AD pathology can be detected, characterized, and followed in vivo.",adult;aged;Alzheimer disease;article;clinical article;controlled study;hippocampus;human;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;relaxation time,"Kirsch, S. J.;Jacobs, R. W.;Butcher, L. L.;Beatty, J.",1992,,,0,
3316,Thrombosis of a Drainage Vein in Developmental Venous Anomaly (DVA) Leading Venous Infarction: A Case Report and Review of the Literature,"Developmental venous anomalies (DVAs) are common congenital venous drainage anomalies. Although they typically have a benign clinical course and a low symptomatic rate, thrombosis of a drainage vein may occur, leading to potentially debilitating complications. We report imaging findings of posterior fossa DVA with a thrombosed drainage vein in a patient with nonhemorrhagic cerebellar infarct. We also review the relevant literature on the subject. © 2009 by the American Society of Neuroimaging.",,"Kiroglu, Y.;Oran, I.;Dalbasti, T.;Karabulut, N.;Calli, C.",2011,April,,0,
3317,Dementia with leukoencephalopathy in systemic lupus erythematosus,"Neurologic manifestations, afflicting up to 70% of SLE patients, include psychosis, seizures, chorea, neuropathies, and stroke. MRI is useful in evaluation of lupus patients and several reports have documented cerebral atrophy or focal hyperintensities. We report an unusual MRI appearance in a 56-year-old woman with SLE, diagnosed on the basis of pleuritis, lymphopenia, anti-DNA antibodies, and neurologic involvement. She reported recent onset of Raynaud's phenomenon and generalized macular rash. She presented after two months of gradual deterioration with memory loss, flattened affect, dysphagia, dysarthria, anomia, and somnolence, without focal neurologic signs. Investigations included elevated ESR, reduced complement, normal CSF without oligoclonal bands, negative viral serology, normal hormone and vitamin levels, normal renal and hepatic function. Neuropsychologic testing showed widespread impairment (WAIS-R: FSIQ-63; WMS-69; DRS-98; RCPM-14; WAB AQ-78.8). CT was normal but MRI showed strikingly symmetric, confluent hyperintensities extensively involving cerebral and cerebellar white matter on T1 and T2 weighted scans. Basal ganglia and subependymal and subcortical white matter were spared. Treated with prednisone, the patient made a gradual, but incomplete, recovery. These MRI findings may reflect widespread vasculopathy or direct immunologic brain insult with or without immunologic blood-brain barrier disruption.",adult;article;brain disease;case report;computer assisted tomography;human;leukoencephalopathy;male;neuropsychology;priority journal;systemic lupus erythematosus,"Kirk, A.;Kertesz, A.;Polk, M. J.",1991,,,0,
3318,An association of human T-cell lymphotropic virus type I infection with vascular dementia,"Subjects ranging in age from 50 to 89 years old, either with or without dementia were studied by both ELISA for anti-human T-cell lymphotropic virus type I (HTLV-I) gag 100-130 antibody and by cranial CT in order to clarify the relationship between HTLV-I infection and dementia. The frequency of anti-HTLV-I antibody was found to be significantly higher in the patients with dementia (24/130, 18.5%) than in those without dementia (11/139, 7.9%) (P=0.0169). Among the various types of dementia, HTLV-I seropositivity was found to be significantly associated with vascular dementia (11/48, 23%) (P=0.0087), but not with Alzheimer type dementia. In addition, HTLV-I seropositivity was also associated with Babinski sign, and the severity of cerebral infarction, ventricular dilatation and periventricular lucency on CT. The presence of HTLV-I therefore appears to be one of the risk factors for vascular dementia in HTLV-I endemic areas.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/virology;Dementia, Vascular/diagnosis/*virology;Endemic Diseases;Female;HTLV-I Infections/diagnosis/*virology;Human T-lymphotropic virus 1/*pathogenicity;Humans;Japan;Male;Middle Aged;Neurologic Examination;Risk Factors;Tomography, X-Ray Computed;Virulence","Kira, J.;Hamada, T.;Kawano, Y.;Okayama, M.;Yamasaki, K.",1997,Nov,,0,
3319,Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study,"BACKGROUND AND OBJECTIVES: Regional cerebral atrophy occurs in carriers of the Huntington's disease (HD) gene mutation before clinical diagnosis is possible. The current inability to reliably measure progression of pathology in this preclinical phase impedes development of therapies to delay clinical onset. We hypothesised that longitudinal statistical imaging would detect progression of structural pathology in preclinical carriers of the HD gene mutation, in the absence of measurable clinical change. METHODS: Thirty subjects (17 preclinical mutation positive, 13 mutation negative) underwent serial clinical and magnetic resonance imaging (MRI) assessments over an interval of 2 years. Statistically significant changes in regional grey and white matter volume on MRI were analysed using tensor based morphometry (TBM). This technique derives a voxel-wise estimation of regional tissue volume change from the deformation field required to warp a subject's early to late T1 images. RESULTS: Over 2 years, there was progressive regional grey matter atrophy in mutation-positive relative to negative subjects, without significant clinical progression of disease. Significant grey matter volume loss was limited to bilateral putamen and globus pallidus externa (GPe), left caudate nucleus, and left ventral midbrain in the region of the substantia nigra. CONCLUSIONS: While these results are consistent with previous cross sectional pathologic and morphometric studies, significant progression of atrophy in HD before the onset of significant clinical decline is now demonstrable with longitudinal statistical imaging. Such measures could be used to assess the efficacy of potential disease modifying drugs in slowing the progression of pathology before confirmed clinical onset of HD.",Adult;Atrophy/pathology;Brain/ pathology;Caudate Nucleus/pathology;Disease Progression;Female;Follow-Up Studies;Globus Pallidus/pathology;Humans;Huntington Disease/epidemiology/genetics/ pathology;Incidence;Magnetic Resonance Imaging;Male;Mesencephalon/pathology;Point Mutation/genetics;Putamen/pathology;Substantia Nigra/pathology;Trinucleotide Repeats/genetics,"Kipps, C. M.;Duggins, A. J.;Mahant, N.;Gomes, L.;Ashburner, J.;McCusker, E. A.",2005,May,10.1136/jnnp.2004.047993,0,
3320,Hereditary diffuse leukoencephalopathy with axonal spheroids caused by R782H mutation in CSF1R: Case report,"We report a biopsy-proven and genetically determined case with leukoencephalopathy showing autosomal dominant inheritance and pre-senile dementia. A 51-year old woman gradually developed a decline in cognitive functions with aphasia and epileptic seizures. Four of her family members were diagnosed as having dementia in their forties to sixties. Five years later she became apathetic and bed-ridden. Brain MRI initially showed fronto-temporal dominant cerebral atrophy with multiple small lacunar-like lesions in the deep white matter, but these white matter lesions became diffuse at an advanced stage. Such possibilities as hereditary vascular or fronto-temporal dementia were clinically suspected, but her family members requested a definitive diagnosis. Brain biopsy showed severe loss of myelin and axons in the white matter with relatively preserved cortical structure. The remaining axons disclosed irregular shapes with the formation of many spheroids, and these findings were consistent with a histopathological diagnosis of neuroaxonal dystrophy. DNA analysis disclosed a novel heterozygous c.2345 G > A (p.782Arg > His) mutation in exon 18 of the colony stimulating factor 1 receptor gene (CSF1R). Hereditary diffuse leukoencephalopathy with axonal spheroids should be included in the differential diagnosis of familial occurrence of pre-senile dementia. © 2012 Elsevier B.V. All rights reserved.",colony stimulating factor receptor;adult;apathy;article;autosomal dominant inheritance;brain atrophy;brain biopsy;case report;cognitive defect;diabetes mellitus;DNA determination;electron microscopy;epilepsy;female;gene mutation;hand grip;hereditary diffuse leukoencephalopathy with axonal spheroid;histology;human;hyperlipidemia;hyperreflexia;hypertension;immunohistochemistry;leukoencephalopathy;Mini Mental State Examination;multiinfarct dementia;mutism;nuclear magnetic resonance imaging;priority journal;quadriplegia;tendon reflex;verbal communication,"Kinoshita, M.;Yoshida, K.;Oyanagi, K.;Hashimoto, T.;Ikeda, S. I.",2012,,,0,
3321,Corpus callosum atrophy in patients with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids: an MRI-based study,"OBJECTIVE: Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. METHODS: We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. RESULTS: All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p<0.01; with non-CNS group, p<0.01). CONCLUSION: This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.","Adult;Aged;Atrophy/pathology;Corpus Callosum/ pathology;Female;Humans;Leukoencephalopathies/diagnosis/epidemiology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Retrospective Studies","Kinoshita, M.;Kondo, Y.;Yoshida, K.;Fukushima, K.;Hoshi, K.;Ishizawa, K.;Araki, N.;Yazawa, I.;Washimi, Y.;Saitoh, B.;Kira, J.;Ikeda, S.",2014,,,0,
3322,Course of cerebral amyloid angiopathy-related inflammation,"BACKGROUND: A subset of patients with cerebral amyloid angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. OBJECTIVE: To analyze the risk factors, diagnostic characteristics, and long-term course of this disorder. METHODS: We assessed 14 consecutive patients with pathologically diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up data. Patients were evaluated for MRI appearance, APOE genotype, and clinical course over a 46.8 +/- 29.1-month follow-up. RESULTS: Baseline MRI scans were characterized by asymmetric T2-hyperintense lesions extending to the subcortical white matter and occasionally the overlying gray matter, with signal properties suggesting vasogenic edema. Subjects could be divided into three groups based on response to immunosuppressive treatment: monophasic improvement (7/12), initial improvement followed by symptomatic relapse (3/12), and no evident response to treatment (2/12). The volume of MRI hyperintensities correlated with the severity of clinical symptoms. One patient experienced symptomatic intracerebral hemorrhage within a region of recurrent MRI hyperintensity. The APOE epsilon4/epsilon4 genotype was strongly associated with CAA-related inflammation, present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but noninflammatory CAA (p < 0.0001). CONCLUSION: Cerebral amyloid angiopathy-related inflammation represents a clinically, pathologically, radiographically, and genetically distinct disease subtype with implications for clinical practice and ongoing immunotherapeutic approaches to Alzheimer disease.","Aged;Alzheimer Disease/immunology/therapy;Anti-Inflammatory Agents/therapeutic use;Apolipoprotein E4/genetics;Cerebral Amyloid Angiopathy/*complications/drug;therapy/genetics/pathology/radiography;Cognition Disorders/etiology;Cohort Studies;Dementia, Vascular/etiology;Disease Progression;Female;Follow-Up Studies;Genotype;Headache/etiology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Seizures/etiology;Vasculitis/*etiology/pathology","Kinnecom, C.;Lev, M. H.;Wendell, L.;Smith, E. E.;Rosand, J.;Frosch, M. P.;Greenberg, S. M.",2007,Apr 24,10.1212/01.wnl.0000260066.98681.2e,0,
3323,Fractal dimension analysis of the cortical ribbon in mild Alzheimer's disease,"Fractal analysis methods are used to quantify the complexity of the human cerebral cortex. Many recent studies have focused on high resolution three-dimensional reconstructions of either the outer (pial) surface of the brain or the junction between the gray and white matter, but ignore the structure between these surfaces. This study uses a new method to incorporate the entire cortical thickness. Data were obtained from the Alzheimer's Disease (AD) Neuroimaging Initiative database (Control N=35, Mild AD N=35). Image segmentation was performed using a semi-automated analysis program. The fractal dimension of three cortical models (the pial surface, gray/white surface and entire cortical ribbon) were calculated using a custom cube-counting triangle-intersection algorithm. The fractal dimension of the cortical ribbon showed highly significant differences between control and AD subjects (p<0.001). The inner surface analysis also found smaller but significant differences (p<0.05). The pial surface dimensionality was not significantly different between the two groups. All three models had a significant positive correlation with the cortical gyrification index (r>0.55, p<0.001). Only the cortical ribbon had a significant correlation with cortical thickness (r=0.832, p<0.001) and the Alzheimer's Disease Assessment Scale cognitive battery (r=-0.513, p=0.002). The cortical ribbon dimensionality showed a larger effect size (d=1.12) in separating control and mild AD subjects than cortical thickness (d=1.01) or gyrification index (d=0.84). The methodological change shown in this paper may allow for further clinical application of cortical fractal dimension as a biomarker for structural changes that accrue with neurodegenerative diseases.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/psychology;Cerebral Cortex/ pathology;Databases, Factual;Female;Fractals;Gyrus Cinguli/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Models, Statistical;Neuropsychological Tests;ROC Curve;Reproducibility of Results;Sex Characteristics","King, R. D.;Brown, B.;Hwang, M.;Jeon, T.;George, A. T.",2010,Nov 1,10.1016/j.neuroimage.2010.06.050,0,
3324,Diffusion MRI measured white matter microstructure as a biomarker of neurodegeneration in preclinical Huntington's disease,"BACKGROUND: Huntington's disease is a progressive neurodegenerative disease, genetically determined by CAG trinucleotide expansions in the IT15 gene. The onset of the symptoms is related to the number of CAG triplets. Because the patients are asymptomatic in the early phase of the disease, in vivo biomarkers are needed to follow up the reurodegeneration and to test putative neuroprotective approaches. One such promising biomarker is the diffusion MRI measured microstructural alteration of the white matter. METHODS: Seven presymtomatic, mutation carriers and ten age-matched healthy controls were included in the study. Diffusion parameters were compared between groups and correlated with measures describing neurodegeneration. In order to reduce the possible misregistration bias due to atrophy the analysis was restricted to the core of each fibre bundles as defined by maximal fractional anisotropy (Tract-Based Spatial Statistics). RESULTS: Decreased fractional anisotropy, along with increased mean, parallel and perpendicular diffusivity was found in white matter tracts, mainly in the corpus callosum. An inverse correlation was detected between the fractional anisotropy and neurodegeneration score (derived from the number of CAG triplets and the patient age) from the areas of the left precentral gyrus, frontal lobe, corpus callosum and the capsula extrema. Altered diffusion parameters are promising biomarkers of the neurodegeneration in Huntington's disease.","Adult;Anisotropy;Biomarkers;Brain/*ultrastructure;Case-Control Studies;Corpus Callosum/ultrastructure;*Diffusion Magnetic Resonance Imaging;Female;Humans;Huntington Disease/*diagnosis/pathology;Male;Middle Aged;Nerve Fibers, Myelinated/*ultrastructure","Kincses, Z. T.;Szabo, N.;Toth, E.;Zadori, D.;Farago, P.;Nemeth, D.;Janacsek, K.;Babos, M.;Klivenyi, P.;Vecsei, L.",2013,Nov 30,,0,
3325,"The pattern of diffusion parameter changes in Alzheimer's disease, identified by means of linked independent component analysis","Several recent studies have indicated that white matter is affected in Alzheimer's disease (AD). Diffusion tensor imaging is a tool by which the white matter microstructure can be examined in vivo, and might offer a possibility for the identification of the pattern of white matter disintegration in AD. In the current analysis, we made use of a novel model-free analysis approach of linked independent component analysis to identify a motif of diffusion parameter alterations exemplifying AD. Analysis of the diffusion data of 16 AD patients and 17 age-matched healthy subjects revealed six independent components, two of which demonstrated differences between the patients and controls. Component #0 was dominated by axial diffusivity, but significant alterations in fractional anisotropy and mean and radial diffusivity were also detected. Alterations were found in regions of crossing of major white matter pathways, such as forceps, corona radiate, and superior longitudinal fascicle, as well as medio-temporal white matter. These results lend support to the coexistence of white matter disintegration of the late myelinating associating fibers and wallerian degeneration-related disintegration, in accordance with the retrogenesis and wallerian degeneration hypothesis.",Aged;Alzheimer Disease/ pathology;Brain/ pathology;Case-Control Studies;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Male;Principal Component Analysis,"Kincses, Z. T.;Horinek, D.;Szabo, N.;Toth, E.;Csete, G.;Stepan-Buksakowska, I.;Hort, J.;Vecsei, L.",2013,,10.3233/jad-122431,0,
3326,A structural MRI study of cholinergic pathways and cognition in multiple sclerosis,"Background: White matter hyperintensities (WMH) in the cholinergic pathways are associated with cognitive performance in Alzheimer's disease. This study aimed to evaluate the relationship between the volume reduction of cholinergic pathways and cognitive function in patients with multiple sclerosis (MS). Methods: Thirty-two MS patients underwent a brain MRI and cognitive measurements including the Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The extent of WMH within the cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS). Computerized WMH volumes were also obtained. FreeSurfer was used to measure regional volumes including the cortical and subcortical volumes. The correlations among the CHIPS, the WMH volume, and the clinical data were assessed, in addition to the correlations between the cognitive scores and regional volumes measured by FreeSurfer. Results: The CHIPS score and the WMH volume were strongly positively correlated with each other (r = 0.87, P < 0.001). The CHIPS score had significantly negative correlations with the MMSE (r = - 0.49, P = 0.003) and the MoCA-J (r = - 0.47, P = 0.005) results. The WMH volume had significantly negative correlations with the MMSE (r = - 0.54, P = 0.001) and the MoCA-J (r = - 0.57, P < 0.001) results. In the analysis by FreeSurfer, both the MMSE and MoCA-J scores had significant positive correlations only with the volume of the corpus callosum. Conclusions: The CHIPS score tended to be less sensitive to the WMH volume in cognitive function evaluation, although the difference did not reach the level of statistical significance. Thus the CHIPS method may not be as effective in MS patients.",Chips;Cholinergic pathway;Cognitive impairment;Multiple sclerosis,"Kimura, Y.;Sato, N.;Ota, M.;Maikusa, N.;Maekawa, T.;Sone, D.;Enokizono, M.;Sugiyama, A.;Imabayashi, E.;Matsuda, H.;Okamoto, T.;Yamamura, T.;Sugimoto, H.",2017,Sep,,0,
3327,A case of senile depression with dysarthria due to trimebutine maleate,"Trimebutine maleate is a gastroenteric motor modulator which improves abnormal peristaltic movements through the direct effect on the smooth muscle cells. We examined a case of senile depression with dysarthria due to trimebutine maleate. The patient was a 67-year-old female. At the age of 65, she became depressive state without any causes and some nontricyclic antidepressants gave her no relief from the depression and induced side effects (drowsiness, dry mouth and dysarthria). When she was 66 years old, she was given trimebutine maleate (100 mg) for her irritable colon syndrome. After several hours of the administration, she suffered from dysarthria and finger tremor. Quitting trimebutine maleate stopped the symptoms a few days later. The cranial CT findings before the occurrence of dysarthria showed cavum septi pellucidi, cavum Vergae, calcifications in bilateral basal gangilas and mild atrophy of cerebral cortices and the findings after the occurrence had no change. Cerebral hemorrhage and infarction were ruled out by her CT findings and the other drugs were unlikely to cause the dysarthria. Therefore, trimebutine maleate might induce the dysarthria which seemes to be the breakdown of the balance dopaminergic and cholinergic systems in the brain. Moreover, it is speculated that her dispositional frailty of the central nervous system and the cerebral organic changes by cavum septi pellucidi, the calcifications and aging underlay the apperance of the dysarthria.",cloxazolam;sulpiride;trimebutine maleate;aged;article;case report;depression;drowsiness;dysarthria;female;human;irritable colon;oral drug administration;senility;tremor,"Kimura, T.;Yoshida, H.;Wada, Y.;Ueda, K.;Deshimaru, M.",1994,,,0,
3328,Two cases of Alzheimer's disease showing deterioration of behavioral and psychological symptoms of dementia induced by switching from rivastigmine to donepezil,"Rivastigmine, galantamine, and memantine, in addition to donepezil, which has been on the market over 10 years, have been available for the treatment of Alzheimer's disease (AD) since 2011 in Japan, leading a new stage in the medical treatment of AD. We studied two AD patients showing sudden deterioration of behavioral and psychological symptoms of dementia (BPSD) associated with switching from rivastigmine to donepezil after the clinical trial of rivastigmine. In the patients, rivastigmine seemed to be more beneficial than donepezil for the control of BPSD. Although It was not obvious whether their different responses to the two cholinesterase inhibitors were due to the different pharmacological profiles, i.e., the presence of inhibition of butyrylcholinesterase in rivastigmine, a particular cholinesterase inhibitor might be more effective in particular AD cases. Further investigations are needed to confirm the difference, and to identify the measures for selecting the most appropriate medication for each AD patient. 2013 Kimura and Takamatsu, publisher and licensee Dove Medical Press Ltd.",adult // aged // aggressiveness // agitation // Alzheimer disease/di [Diagnosis] // Alzheimer disease/dt [Drug Therapy] // article // blood examination // brain blood flow // brain cortex // case report // cingulate gyrus // clinical examination // cogn,"Kimura, T.;Takamatsu, J.",2012,,10.2147/ndt.s37688,0,
3329,Relationship between White Matter Lesions and Progression of Cognitive Decline in Alzheimer's Disease,"BACKGROUND: This study examined the relationship between baseline white matter lesions (WMLs) and the progression of cognitive decline in patients with late-onset Alzheimer's disease (AD). METHODS: Fifty-six patients with AD were included in the study (23 men, 33 women; mean age, 77.8 years). All subjects were treated with acetylcholinesterase inhibitors and followed up for approximately 1 year. The Mini-Mental State Examination (MMSE) score was assessed at least twice to evaluate the progressive cognitive impairment. All subjects underwent brain MRI at baseline and were divided into WMLs(-), mild WMLs(+), and moderate WMLs(+) groups based on WML severity. Changes in MMSE scores between baseline and follow-up were analyzed using the Wilcoxon signed-rank test. RESULTS: MMSE scores at baseline did not differ significantly among the three groups (p = 0.1658), whereas MMSE scores at the follow-up evaluation were significantly lower in the moderate WMLs(+) group than in the WMLs(-) group (p = 0.0257). The mean MMSE scores remained above baseline values during the approximately 1-year follow-up in the WMLs(-) group, whereas they were decreased in the mild and moderate WMLs(+) groups. Moreover, the frequency of improvement in patients from the WMLs(-) group tended to be higher than that in patients from the WMLs(+) groups. CONCLUSION: Baseline WMLs may be associated with the heterogeneous progression of cognitive decline in patients with AD.",Acetylcholinesterase inhibitor;Alzheimer's disease;Mri;Rate of cognitive decline;White matter lesions,"Kimura, N.;Nakama, H.;Nakamura, K.;Aso, Y.;Kumamoto, T.",2013,Jan,10.1159/000350317,0,
3330,Effect of white matter lesions on brain perfusion in Alzheimer's disease,"BACKGROUND: This study examined the effect of white matter lesions (WMLs) on regional cerebral blood flow (rCBF) in patients with Alzheimer's disease (AD). METHODS: Ninety-eight patients with AD were included in the study (40 men and 58 women; mean age, 78.1 years). Cognitive function was assessed using the Mini-Mental State Examination. Brain magnetic resonance imaging (MRI) and (99m)Tc ethyl cysteinate dimer single photon emission computed tomography were performed in all subjects. AD patients were divided into two subgroups according to the presence of WMLs on MRI. A voxel-by-voxel group analysis using Statistical Parametric Mapping 8 was used to detect the differences in rCBF between the two groups. RESULTS: Fifty-seven of 98 AD patients (58%) showed mild to moderate WMLs on MRI. The prevalence of hypertension was significantly higher in AD patients with WMLs than in those without WMLs. AD patients with WMLs exhibited a significantly decreased rCBF in the anterior cingulate gyrus and insula, compared to AD patients without WMLs. CONCLUSION: We suggest that WMLs might influence brain regions associated with the limbic system in patients with AD.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/ physiopathology;Brain/ blood supply/radionuclide imaging;Cerebrovascular Circulation/ physiology;Female;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/ physiopathology/radiography;Magnetic Resonance Imaging/methods;Male;Neuroimaging/instrumentation/methods;Neuropsychological Tests;Technetium;Tomography, Emission-Computed, Single-Photon/methods","Kimura, N.;Nakama, H.;Nakamura, K.;Aso, Y.;Kumamoto, T.",2012,,10.1159/000345184,0,
3331,Portal-systemic shunt encephalopathy presenting with diffuse cerebral white matter lesion: An autopsy case,"We report herein an autopsy case of portal-systemic encephalopathy (PSE) presenting with diffuse tissue rarefaction in the cerebral deep white matter. Clinically, the patient showed recurrent episodes of unconsciousness, abnormal behavior and urinary incontinence, as well as flapping tremor. Cognitive impairment and peripheral neuropathy developed following recurrent episodes. Although conventional arterial portography revealed a small portal-systemic collateral vessel of a left gastro-renal venous shunt, abdominal CT and liver biopsy showed no evidence of liver cirrhosis and serum ammonia level showed a mild increase. T2-weighted MRI demonstrated symmetrical signal hyperintensities in the deep white matter. Neuropathological findings showed Alzheimer type II astrocytes in the deep layers of the cerebral cortices and severe tissue rarefaction with no or slight reactive astrocytosis in the subcortical and deep white matter. These white matter changes have been reported infrequently in patients with PSE. The present case suggests that chronic PSE without liver cirrhosis may develop diffuse white matter lesions. © 2008 Japanese Society of Neuropathology.",Alzheimer disease;ammonia blood level;article;astrocyte;astrocytosis;autopsy;behavior disorder;brain damage;cognitive defect;flapping tremor;hepatic encephalopathy;histopathology;human;nuclear magnetic resonance imaging;peripheral neuropathy;portal phlebography;priority journal;unconsciousness;urine incontinence;white matter,"Kimura, N.;Kumamoto, T.;Hanaoka, T.;Nakamura, K.;Hazama, Y.;Arakawa, R.",2008,,,0,
3332,Comparison of cerebrospinal fluid profiles in Alzheimer's disease with multiple cerebral microbleeds and cerebral amyloid angiopathy-related inflammation,"Brain magnetic resonance imaging (MRI) of patients with Alzheimer's disease (AD) sometimes reveals multiple cerebral microbleeds (CMBs) and confluent white matter hyperintensities (WMHs) similar to those observed in cerebral amyloid angiopathy-related inflammation (CAA-I). To determine whether there might be common pathophysiological mechanisms underlying the MRI findings of multiple CMBs and confluent WMHs, we investigated the cerebrospinal fluid (CSF) profiles of 38 AD, five amnestic mild cognitive impairment (MCI), and six CAA-I patients. The AD and MCI patients were divided into groups of patients with (n = 10) or without (n = 33) multiple CMBs (n >/= 2) on T2*-gradient echo sequences of brain MRI. We compared the CSF profiles of AD and MCI patients with or without multiple CMBs, and CAA-I patients. The brain MRIs of the patients with multiple CMBs revealed severe degrees of WMHs compared with the patients without multiple CMBs. The levels of CSF anti-amyloid beta autoantibody and interleukin 8, and CSF/serum albumin ratios and immunoglobulin G indexes, were significantly higher in CAA-I patients than the other groups. However, there were no significant differences in the CSF profiles of patients with or without multiple CMBs. Our study provides evidence for different pathophysiological mechanisms underlying these differential MRI findings in AD and CAA-I.",Alzheimer's disease;Cerebral amyloid angiopathy;Inflammation;Microbleed;White matter hyperintensity,"Kimura, A.;Takemura, M.;Saito, K.;Yoshikura, N.;Hayashi, Y.;Harada, N.;Nishida, H.;Nakajima, H.;Inuzuka, T.",2017,Feb,,0,
3333,CADASIL versus multiple sclerosis,"This case history reports on the second family in Denmark to be diagnosed with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy). Due to symptoms, signs and paraclinical findings, an initial diagnosis of multiple sclerosis was made. However, MRI findings of leucoencephalopathy in the external capsule and anterior temporal lobes together with negative CSF findings and family history raised suspicions of CADASIL. Skin biopsy with granular osmiophilic material (GOM) and genetic testing showing the NOTCH 3 mutation proved the diagnosis. There is considerable variability in the symptoms of CADASIL; however, most often a family history of migraine, cerebrovascular events and dementia in early life is found.",article;CADASIL;cerebrospinal fluid;cerebrovascular disease;dementia;Denmark;family history;genetic analysis;human;leukoencephalopathy;migraine;multiple sclerosis;nuclear magnetic resonance imaging;skin biopsy;symptomatology,"Kimper-Karl, A. C.;Jensen, H. B.;Kristensen, O.",2006,,,0,
3334,Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy,"BACKGROUND: Neuropathologic studies suggest an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages. We examined the prevalence and associated risk factors for infarcts detected by diffusion-weighted imaging (DWI). METHODS: We performed retrospective analysis of MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts. We also examined the association between DWI lesions and demographic variables, conventional vascular risk factors, and radiographic markers of CAA severity such as number of hemorrhages on gradient-echo MRI and volume of T2-hyperintense white matter lesions. RESULTS: Twelve of 78 subjects with CAA (15%) had a total of 17 DWI-hyperintense lesions consistent with subacute cerebral infarctions vs 0 of 55 subjects with AD/MCI (p = 0.001). The DWI lesions were located primarily in cortex and subcortical white matter. CAA subjects with DWI lesions had a higher median number of total hemorrhages (22 vs 4, p = 0.025) and no difference in white matter hyperintensity volume or conventional vascular risk factors compared to subjects with CAA without lesions. CONCLUSIONS: MRI evidence of small subacute infarcts is present in a substantial proportion of living patients with advanced cerebral amyloid angiopathy (CAA). The presence of these lesions is associated with a higher burden of hemorrhages, but not with conventional vascular risk factors. This suggests that advanced CAA predisposes to ischemic infarction as well as intracerebral hemorrhage.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Brain/pathology;Cerebral Amyloid Angiopathy/ complications/pathology;Cerebral Hemorrhage/ etiology/pathology;Cerebral Infarction/ etiology/pathology;Cognition Disorders/complications/pathology;Cross-Sectional Studies;Data Collection;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Interpretation, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Retrospective Studies","Kimberly, W. T.;Gilson, A.;Rost, N. S.;Rosand, J.;Viswanathan, A.;Smith, E. E.;Greenberg, S. M.",2009,Apr 7,10.1212/01.wnl.0000345666.83318.03,0,
3335,Relation between the clock drawing test (CDT) and structural changes of brain in dementia,"The CDT is a useful screening instrument for assessing cognition. The aim of this study is to identify which structural change of the brain is related with the CDT performance. Eighty-four patients with memory impairment were enrolled. The Korean versions of the mini-mental state examination (K-MMSE) and the modified mini-mental state (3MS) test, and the Seoul Neuropsychological Screening Battery (SNSB) were given to every subject. Four CDT scoring methods were used. The cerebral white matter hyperintensity (WMH), cortical atrophy (CA), ventricular enlargement (VE), and medial temporal lobe atrophy (MTA) were rated by two neurologists who were kept ""blind"" to the clinical information. The cognitive and executive functions were significantly correlated with the CDT performance. The degree of WMH and MTA showed an inverse relation with the CDT performance. The periventricular WMH (PVH) contributed more to impairment of CDT, than that of the deep WMH (DWMH). This study suggests that a combination of executive dysfunction via the frontal-subcortical disruption due to the PVH and memory impairment due to the MTA might be responsible for further worsening on the CDT.","Adult;Aged;Aged, 80 and over;Cerebral Ventricles/*pathology;Cohort Studies;Dementia/diagnosis/*pathology;Female;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Psychomotor Performance","Kim, Y. S.;Lee, K. M.;Choi, B. H.;Sohn, E. H.;Lee, A. Y.",2009,Mar-Apr,10.1016/j.archger.2008.01.010,0,
3336,Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study,"Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer's disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-ss burden was quantified by PiB standardized uptake value ratio (SUVR), and the amount of small vessel disease was quantified by number of lacune and small vessel disease score on MRI. We also measured cortical thickness. During the three years of follow-up, compared to the APOE3 homozygotes, there was less increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype did not show significant effects on small vessel disease progression. APOE2 carriers also showed less cortical thinning (p = 0.023) and a slower rate of cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our findings suggest that, in svMCI patients, APOE2 has protective effects against amyloid-ss accumulation, cortical thinning, and cognitive decline.",,"Kim, Y. J.;Seo, S. W.;Park, S. B.;Yang, J. J.;Lee, J. S.;Lee, J.;Jang, Y. K.;Kim, S. T.;Lee, K. H.;Lee, J. M.;Lee, J. H.;Kim, J. S.;Na, D. L.;Kim, H. J.",2017,May 15,,0,
3337,White matter microstructural changes in pure Alzheimer's disease and subcortical vascular dementia,"BACKGROUND AND PURPOSE: Recent studies have demonstrated that Alzheimer's disease (AD) and subcortical vascular dementia (SVaD) have white matter (WM) microstructural changes. However, previous studies on AD and SVaD rarely eliminated the confounding effects of patients with mixed Alzheimer's and cerebrovascular disease pathologies. Therefore, our aim was to evaluate the divergent topography of WM microstructural changes in patients with pure AD and SVaD. METHODS: Patients who were clinically diagnosed with AD and SVaD were prospectively recruited. Forty AD patients who were Pittsburgh compound B (PiB) positive [PiB(+) AD] without WM hyperintensities and 32 SVaD patients who were PiB negative [PiB(-) SVaD] were chosen. Fifty-six cognitively normal individuals were also recruited (NC). Tract-based spatial statistics of diffuse tensor imaging were used to compare patterns of fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Compared with the NC group, the PiB(+) AD group showed decreased FA in the bilateral frontal, temporal and parietal WM regions and the genu and splenium of the corpus callosum as well as increased MD in the left frontal and temporal WM region. PiB(-) SVaD patients showed decreased FA and increased MD in all WM regions. Direct comparison between PiB(+) AD and PiB(-) SVaD groups showed that the PiB(-) SVaD group had decreased FA across all WM regions and increased MD in all WM regions except occipital regions. CONCLUSION: Our findings suggest that pure AD and pure SVaD have divergent topography of WM microstructural changes including normal appearing WM.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Aniline Compounds;Dementia, Vascular/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Middle Aged;Thiazoles;White Matter/ pathology","Kim, Y. J.;Kwon, H. K.;Lee, J. M.;Kim, H. J.;Jung, N. Y.;Kim, S. T.;Lee, K. H.;Na, D. L.;Seo, S. W.",2015,Apr,10.1111/ene.12645,0,
3338,Spectrum of NOTCH3 mutations in Korean patients with clinically suspicious cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene on chromosome 19. Previous studies showed that NOTCH3 contains mutational hotspots that can vary among individuals of different ethnic backgrounds. In this study, we investigated the spectrum of NOTCH3 mutations in Korean patients with CADASIL. We retrospectively analyzed 156 patients who underwent NOTCH3 gene testing for molecular diagnosis of CADASIL using Sanger sequencing with a tiered approach. First, we screened previously reported mutational hotspots (exons 2-6, 8, 11, 18, 19, and 22). If no mutation was detected and samples were available, we extended our analysis to additional exons (7, 9, 10, 14, 15, 20, 21, 23, and 25). In 45 of 156 patients (28.8%), 29 mutations and 16 novel variants of unknown significance (VUS) were identified. The p.R544C mutation in exon 11 of NOTCH3 was the most frequently observed mutation (n= 8), followed by p.R75P in exon 3 (n= 7), p.R332C in exon 6 (n= 3), p.R54C in exon 2 (n= 2), and p.R90C in exon 3 (n=2). Among the VUS, p.R1175W in exon 22, p.S414C in exon 8, and p.N1207S in exon 22 were found in 5, 3, and 2 patients, respectively. Other mutations and VUS were observed in 1 patient each. Although this was not a prospective, nationwide cohort study, the results above suggested that the spectrum of NOTCH3 mutations might be different in Koreans than in individuals of Caucasian ethnicity. Therefore, further analysis of Koreans with CADASIL might be necessary to implement a Korean-specific mutation screening paradigm. © 2014 Elsevier Inc.",Notch3 receptor;adult;aged;article;brain ischemia;CADASIL;cognitive defect;controlled study;depression;ethnic group;exon;female;gene mutation;genetic analysis;genetic screening;headache;human;Korean;major clinical study;male;middle aged;molecular diagnosis;NOTCH3 gene;nuclear magnetic resonance imaging;nucleotide sequence;priority journal;retrospective study,"Kim, Y. E.;Yoon, C. W.;Seo, S. W.;Ki, C. S.;Kim, Y. B.;Kim, J. W.;Bang, O. Y.;Lee, K. H.;Kim, G. M.;Chung, C. S.;Na, D. L.",2014,,,0,
3339,Two novel mutations of the NOTCH3 gene in Korean patients with CADASIL,"Mutations in the NOTCH3 gene (NOTCH3) are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an adult-onset hereditary angiopathy leading to ischemic episodes, vascular dementia and other neurologic deficits. All mutations of NOTCH3 described so far are strictly stereotyped, leading to the gain or loss of a cysteine residue in a given epidermal growth factor (EGF)-like repeat of NOTCH3. We report two novel mutations of NOTCH3, R587C and C988Y, each resulting in an odd number of cysteine residues in an EGF-like repeat of NOTCH3. We identified these mutations in two unrelated Korean families with CADASIL, who presented with magnetic resonance imaging (MRI) abnormalities typical of CADASIL. These findings confirm that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic backgrounds. © 2005 Elsevier B.V. All rights reserved.",,"Kim, Y.;Kim, J. S.;Kim, G.;No, Y. J.;Yoo, H. W.",2006,29,,0,
3340,Characteristics of CADASIL in Korea: A novel cysteine-sparing Notch3 mutation,"OBJECTIVE: To elucidate the phenotype, genotype, and MRI findings of Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and mutation carriers. METHODS: The authors studied 40 members of nine unrelated Korean CADASIL families. After genetic analysis of Notch3, clinical and MRI findings were correlated in 27 mutation carriers. RESULT: Notch3 mutation sites were C174R (one family, n = 3), R133C (one family, n = 3), R587C (one family, n = 1), R544C (two families, n = 5), and R75P (four families, n = 15). The clinical features were typical of CADASIL, but the frequency of migraine in the Korean population appears low. MRI abnormalities were found in 54% of the mutant carriers, the most common being white matter hyperintensities. The prevalence of lacunes and microbleeds increased with patient age. Anterior temporal areas were less often involved in subjects with R75P mutations than in those where mutations occurred in other sites (p = 0.02). Gradient echo imaging identified microbleedings in 33% of mutation carriers (64% of those with abnormal MRI), whereas diffusion-weighted MRI showed abnormal findings in only one patient. Neurologic disability was related to the number of lacunar infarcts and the lesion volume of white matter hyperintensities (p < 0.001) whereas MMSE score was related to the number of lacunar infarcts (p < 0.005). CONCLUSIONS: Although Korean cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mutation carriers show similar clinical and MRI findings, these abnormalities appear less frequently than in other populations. Relatively frequent microbleedings on gradient echo imaging suggest that treatment should be individualized according to MRI findings. The novel mutation of R75P, not involving a cysteine residue, is related to less frequent involvement of the anterior temporal area, thus broadening the spectrum of CADASIL. Copyright © 2006 by AAN Enterprises, Inc.",,"Kim, Y.;Choi, E. J.;Choi, C. G.;Kim, G.;Choi, J. H.;Yoo, H. W.;Kim, J. S.",2006,May,,0,
3341,Striopallidodentate calcification and progressive supranuclear palsy-like phenotype in a patient with idiopathic hypoparathyroidism,"We present a 77-year-old woman with levodopa-nonresponsive parkinsonism, dementia, and supranuclear gaze palsy on vertical and horizontal gaze. Laboratory findings were consistent with idiopathic hypoparathyroidism, and brain computed tomography showed extensive bilateral calcifications of the basal ganglia, centrum semiovale, dentate nuclei, and cerebellar white matter. These results illustrate that striopallidodentate calcification due to hypoparathyroidism may present with symptoms mimicking progressive supranuclear palsy.",Idiopathic hypoparathyroidism;Progressive supranuclear palsy;Striopallidodentate calcification,"Kim, T. W.;Park, I. S.;Kim, S. H.;Lee, K. S.;Kim, Y. I.;Kim, J. S.",2007,Mar,10.3988/jcn.2007.3.1.57,0,
3342,Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia,"BACKGROUND AND PURPOSE: The burden of amyloid beta is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid beta load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. MATERIALS AND METHODS: The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. RESULTS: The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. CONCLUSIONS: This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral microbleeds than did patients with Parkinson disease dementia.",,"Kim, S. W.;Chung, S. J.;Oh, Y. S.;Yoon, J. H.;Sunwoo, M. K.;Hong, J. Y.;Kim, J. S.;Lee, P. H.",2015,Sep,10.3174/ajnr.A4337,0,
3343,"Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease","BACKGROUND AND PURPOSE: Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer's disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients. METHODS: Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2+/-8.8 years, mean+/-SD, n=36) and those with moderate-to-severe WMC (74.6+/-4.6 years, n=36) on brain MRI. RESULTS: In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels >/=12.9 micromol/L - with the bottom tertile - tHcy levels </=9.4 micromol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA. CONCLUSIONS: Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.",,"Kim, S. R.;Choi, S. H.;Ha, C. K.;Park, S. G.;Pyun, H. W.;Yoon, D. H.",2009,Jun,10.3988/jcn.2009.5.2.85,0,
3344,Dementia mimicking a sudden cognitive and behavioral change induced by left globus pallidus infarction: Review of two cases,"Recently there has been increasing interest in the non-motor functions of the globus pallidus, and especially its role in cognitive processing. We experienced two patients with acute cognitive and behavior changes after globus pallidus infarctions. Examination of both revealed inattention, decreased verbal fluency, emotional blunting, and amnesia. There were no other sensory or motor symptoms. Brain magnetic resonance imaging (MRI) showed focal acute cerebral infarction in the left globus pallidus. Neuropsychological assessment revealed decreased frontal executive function, with verbal memory disturbance. These cases suggest that strategic infarction dementia can result from a single globus pallidus lesion. © 2008.",,"Kim, S. H.;Park, K. H.;Sung, Y. H.;Lee, Y. B.;Park, H. M.;Shin, D. J.",2008,15,,0,
3345,Voxel-based analysis of diffusion tensor imaging in patients with subcortical vascular cognitive impairment: correlates with cognitive and motor deficits,"BACKGROUND AND PURPOSE: Patients with small vessel disease show high-signal intensity on T2-weighted magnetic resonance (MR) images that represent ischemic cell damage. However, despite a similar degree of ischemic change, the amount and the severity of clinical presentations may vary. We investigated the clinical correlations of ischemic changes using voxel-based morphometric analyses of diffusion tensor imaging (DTI). METHODS: Twenty-seven MCI and 34 dementia patients were included who all had significant small vessel disease on magnetic resonance imaging (MRI). In all patients, neuropsychological tests, a rating on the Pyramidal and Extrapyramidal scale (PEPS) for motor deficits, and 3-Tesla MRI including DTI scans were performed. Voxel-based analysis of the fractional anisotropy and mean diffusivity maps were computed. RESULTS: Cognitive scores correlated with the DTI abnormalities in supratentorial areas with regional specificity according to each cognitive test. Unexpectedly, cognitive deficits in most neuropsychological tests, even in some frontal tasks, were associated with disruption of posterior white matter integrities. Motor deficits correlated with both supra- and infratentorial lesions. CONCLUSION: Our findings suggest that in patients with small vessel disease who show cognitive and motor impairments, a specific distribution of fiber tract damage is more related with clinical deficits than is the severity of the total ischemia.","Aged;Aged, 80 and over;Brain/ pathology/physiopathology;Cognition Disorders/ pathology/physiopathology;Dementia, Vascular/ pathology/physiopathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Neuropsychological Tests","Kim, S. H.;Park, J. S.;Ahn, H. J.;Seo, S. W.;Lee, J. M.;Kim, S. T.;Han, S. H.;Na, D. L.",2011,Oct,10.1111/j.1552-6569.2010.00527.x,0,
3346,The effect of ischemic cholinergic damage on cognition in patients with subcortical vascular cognitive impairment,"Prior research has shown that the total amount of white matter ischemia had no significant correlation with cognitive deficits. We compared the association of white matter hyperintensities (WMHs) of total as well as cholinergic pathways with clinical dementia severity and investigated whether cholinergic ischemic burden had an independent predictive value with respect to cognitive decline in subcortical vascular cognitive impairment (SVCI). Forty-eight patients underwent detailed neuropsychological tests and brain magnetic resonance imaging. Quantification of WMH in the total white matter and in cholinergic pathways was achieved using the visual Scheltens scale and Cholinergic Pathway HyperIntensity Scale (CHIPS), respectively. We explored the association between WMH scores and clinical dementia rating scale (CDR). To assess the relation between WMH and cognitive scores, multiple linear regression analysis was used. The CHIPS score was higher in subcortical vascular dementia compared to subcortical vascular MCI, while this difference was not found with the total TMHs (TWMH) score. The TWMH score had a positive correlation with CHIPS, however only CHIPS scores positively correlated with sum of box scores of CDR scale (CDR SB; rho = .474, P = .001). Higher CHIPS scores were associated with lower performance on the semantic word fluency test (beta = -.447, P = .036), whereas the TWMH scores had no independent predictive value with respect to cognitive impairment, after controlling for CHIPS score. Our data confirmed the association of ischemic damage within cholinergic pathways with dementia severity, independent of TWMH in SVCI. In addition, this cholinergic deficit is clinically relevant to cognitive deterioration, especially with frontal dysfunction.","Aged;Aged, 80 and over;Brain/pathology;Brain Ischemia/pathology/ psychology;Cholinergic Neurons/ pathology;Cognition;Cognition Disorders/ pathology/psychology;Dementia, Vascular/pathology/ psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Severity of Illness Index","Kim, S. H.;Kang, H. S.;Kim, H. J.;Moon, Y.;Ryu, H. J.;Kim, M. Y.;Han, S. H.",2012,Jun,10.1177/0891988712445089,0,
3347,Voxel-based morphometric study of brain volume changes in patients with Alzheimer's disease assessed according to the Clinical Dementia Rating score,"We evaluated the volume reduction of gray matter (GM) and white matter (WM) in patients with an Alzheimer's disease (AD) assessment based on the Clinical Dementia Rating (CDR) score. Patients with AD (n=61), with no subcortical WM ischemia, and healthy control patients (n=33) underwent T1-weighted spoiled gradient echo sequences, which were analyzed using voxel-based morphometry. Global GM volume reduction was observed in patients with a CDR score of 1 or a CDR score of 2, and WM volume reduction was observed in patients with a CDR score of 2. Regional GM volume reduction was found in the right inferior frontal gyrus, bilateral dorso-lateral and medial temporal lobes; WM volume reduction was found in the bilateral temporal subcortex (family-wise error, p<0.01). A CDR score of 0.5 was associated with volume reduction in the left olfactory gyrus. The peak z-score and spatial extent of volume reduction increased with increasing CDR score and were higher on the left side. GM volume reduction increased with increasing CDR scores and suggests a possible pathomechanism of AD.","Aged;Alzheimer Disease/complications/*pathology;Brain/*pathology;*Brain Mapping;Dementia/etiology/*pathology;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Middle Aged;*Neuropsychological Tests","Kim, S.;Youn, Y. C.;Hsiung, G. Y.;Ha, S. Y.;Park, K. Y.;Shin, H. W.;Kim, D. K.;Kim, S. S.;Kee, B. S.",2011,Jul,10.1016/j.jocn.2010.12.019,0,
3348,"Factors related to prevalence, persistence, and incidence of depressive symptoms in mild cognitive impairment: vascular depression construct","OBJECTIVE: Depression is prevalent among elders with cognitive impairment. Cerebral white matter hyperintensities (WMH) have consistently been implicated in late-life depression and in cognitive impairment. This study aims to clarify the factors related to prevalence, persistence, and new onset of depressive symptoms in subjects with mild cognitive impairment (MCI). METHODS: As part of a multicenter prospective study, the Clinical Research Center for Dementia of South Korea (CREDOS) Study, we enrolled 590 subjects diagnosed with MCI and with no prior history of depression. Depressive symptoms were assessed by the Korean version of the Geriatric Depression Scale short form (SGDS-K) at baseline and at follow-up visits. Brain magnetic resonance imaging was performed at baseline to quantify WMH using a visual rating scale. RESULTS: The baseline prevalence of clinically significant depressive symptoms (SGDS-K >/=5) was 51.4%, and this feature was associated with younger age, lower educational achievement, and higher Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Persistence of depressive symptoms across the study period was significantly associated with baseline CDR-SB and depression scores. New onset of depression (SGDS-K >/=8; incidence 15.7%) among subjects free of depressive symptoms (SGDS-K <5) at baseline was associated with severe deep subcortical, but not periventricular, WMH. CONCLUSIONS: In patients with MCI aged 50 years or older, depressive symptoms were highly prevalent. Cognitive status was closely related to both prevalence and persistence of depressive symptoms, while new onset of depression was associated with deep subcortical WMH severity in this MCI cohort. Our findings provide prospective evidence consistent with the vascular depression hypothesis. Copyright (c) 2015 John Wiley & Sons, Ltd.","Aged;Aged, 80 and over;Cognitive Dysfunction/ pathology/ psychology;Depressive Disorder/ epidemiology;Female;Humans;Incidence;Magnetic Resonance Imaging;Male;Prevalence;Prospective Studies;Psychiatric Status Rating Scales;Republic of Korea/epidemiology;White Matter/ pathology;depression;depressive symptom;mild cognitive impairment;risk factor;vascular depression;white matter hyperintensities","Kim, S.;Woo, S. Y.;Kang, H. S.;Lim, S. W.;Choi, S. H.;Myung, W.;Jeong, J. H.;Lee, Y.;Hong, C. H.;Kim, J. H.;Na, H.;Carroll, B. J.;Kim, D. K.",2016,Jul,,0,
3349,"Factors related to prevalence, persistence, and incidence of depressive symptoms in mild cognitive impairment: vascular depression construct","OBJECTIVE: Depression is prevalent among elders with cognitive impairment. Cerebral white matter hyperintensities (WMH) have consistently been implicated in late-life depression and in cognitive impairment. This study aims to clarify the factors related to prevalence, persistence, and new onset of depressive symptoms in subjects with mild cognitive impairment (MCI). METHODS: As part of a multicenter prospective study, the Clinical Research Center for Dementia of South Korea (CREDOS) Study, we enrolled 590 subjects diagnosed with MCI and with no prior history of depression. Depressive symptoms were assessed by the Korean version of the Geriatric Depression Scale short form (SGDS-K) at baseline and at follow-up visits. Brain magnetic resonance imaging was performed at baseline to quantify WMH using a visual rating scale. RESULTS: The baseline prevalence of clinically significant depressive symptoms (SGDS-K >/=5) was 51.4%, and this feature was associated with younger age, lower educational achievement, and higher Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Persistence of depressive symptoms across the study period was significantly associated with baseline CDR-SB and depression scores. New onset of depression (SGDS-K >/=8; incidence 15.7%) among subjects free of depressive symptoms (SGDS-K <5) at baseline was associated with severe deep subcortical, but not periventricular, WMH. CONCLUSIONS: In patients with MCI aged 50 years or older, depressive symptoms were highly prevalent. Cognitive status was closely related to both prevalence and persistence of depressive symptoms, while new onset of depression was associated with deep subcortical WMH severity in this MCI cohort. Our findings provide prospective evidence consistent with the vascular depression hypothesis. Copyright (c) 2015 John Wiley & Sons, Ltd.",,"Kim, S.;Woo, S. Y.;Kang, H. S.;Lim, S. W.;Choi, S. H.;Myung, W.;Jeong, J. H.;Lee, Y.;Hong, C. H.;Kim, J. H.;Na, H.;Carroll, B. J.;Kim, D. K.",2015,Dec 17,10.1002/gps.4400,0,3348
3350,Periventricular white matter hyperintensities and the risk of dementia: a CREDOS study,"BACKGROUND: Cerebral white matter hyperintensities (WMH) are prevalent incident findings on brain MRI scans among elderly people and have been consistently implicated in cognitive dysfunction. However, differential roles of WMH by region in cognitive function are still unclear. The aim of this study was to ascertain the differential role of regional WMH in predicting progression from mild cognitive impairment (MCI) to different subtypes of dementia. METHODS: Participants were recruited from the Clinical Research Center for Dementia of South Korea (CREDOS) study. A total of 622 participants with MCI diagnoses at baseline and follow-up evaluations were included for the analysis. Initial MRI scans were rated for WMH on a visual rating scale developed for the CREDOS. Differential effects of regional WMH in predicting incident dementia were evaluated using the Cox proportional hazards model. RESULTS: Of the 622 participants with MCI at baseline, 139 patients (22.3%) converted to all-cause dementia over a median of 14.3 (range 6.0-36.5) months. Severe periventricular WMH (PWMH) predicted incident all-cause dementia (Hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.43-3.43) and Alzheimer's disease (AD) (HR 1.86; 95% CI 1.12-3.07). Subcortical vascular dementia (SVD) was predicted by both PWMH (HR 16.14; 95% CI 1.97-132.06) and DWMH (HR 8.77; 95% CI 1.77-43.49) in more severe form (>/= 10 mm). CONCLUSIONS: WMH differentially predict dementia by region and severity. Our findings suggest that PWMH may play an independent role in the pathogenesis of dementia, especially in AD.",Alzheimer's disease;dementia;mild cognitive impairment;subcortical vascular dementia;white matter hyperintensity,"Kim, S.;Choi, S. H.;Lee, Y. M.;Kim, M. J.;Kim, Y. D.;Kim, J. Y.;Park, J. H.;Myung, W.;Na, H. R.;Han, H. J.;Shim, Y. S.;Kim, J. H.;Yoon, S. J.;Kim, S. Y.;Kim, D. K.",2015,Dec,10.1017/s1041610215001076,0,
3351,Differential diagnosis of idiopathic normal pressure hydrocephalus from other dementias using diffusion tensor imaging,"BACKGROUND AND PURPOSE: Because DTI can provide good markers of white matter pathology, it could be useful in differentiating white matter changes of INPH from those of other dementias. The aim of this study was, by using DTI, to compare the characteristic white matter changes in INPH with those in AD, subcortical vascular dementia, and healthy control subjects. MATERIALS AND METHODS: Sixteen patients with presurgical INPH, 10 with AD, 10 with subcortical vascular dementia, and 20 healthy control subjects underwent DTI. All patients with INPH showed clinical improvement after shunt surgery, and 9 of them also underwent postshunting DTI. Regions of interest were selected at the periventricular white matter, the anterior limb of the internal capsule, the posterior limb of the internal capsule, the genu and the splenium of the corpus callosum, the superior longitudinal fasciculus, and the inferior longitudinal fasciculus. FA and MD were obtained from each region of interest and were compared among the groups. RESULTS: Presurgical INPH showed significantly higher FA than all the other groups in the posterior limb of the internal capsule, which was decreased after shunt surgery. Presurgical MD of the INPH group was higher than that in the AD and healthy control groups but lower than that in the subcortical vascular dementia group in the anterior periventricular white matter, the anterior limb of the internal capsule, and the superior longitudinal fasciculus. In differentiating INPH, the sensitivity and specificity of FA in the posterior limb of the internal capsule was 87.5% and 95.0%, respectively. CONCLUSIONS: Patients with shunt-responsive INPH showed higher FA in the posterior limb of the internal capsule compared with healthy controls and those in other groups of dementia that was reversible with shunt surgery. With this parameter, shunt-responsive INPH could be distinguished from AD, subcortical vascular dementia, and healthy conditions with high diagnostic accuracy.",,"Kim, M. J.;Seo, S. W.;Lee, K. M.;Kim, S. T.;Lee, J. I.;Nam, D. H.;Na, D. L.",2011,September,,0,
3352,Diffusion Tensor Changes According to Age at Onset and Apolipoprotein e Genotype in Alzheimer Disease,"Age at onset is one of the most important factors that affects the clinical course in Alzheimer disease (AD), whereas other factors such as apolipoprotein E (apoE) genotype may also play a major role. In this study, we aimed to investigate the effect of age at onset and apoE genotype on white-matter changes in AD using diffusion tensor imaging. About 213 patients with AD and 66 normal individuals underwent diffusion tensor imaging, and apoE genotype was obtained in all AD patients and in 24 normal individuals. When multiple regression analysis was conducted, a younger age at onset was associated with lower fractional anisotropy in both deep-located long-range limbic and association fibers and superficial-located short-range association fibers in the frontal, the temporal, and the parietal lobes, and with a higher mean diffusivity in deep-located fibers and the bilateral medial thalamus. When analyzed separately in apoE e4 carriers and noncarriers, e4 carriers showed an association between a younger age at onset and lower fractional anisotropy, mainly in deep-located fibers, whereas noncarriers showed this association in both deep-located and superficial-located fibers. There was no difference in the spatial distribution between carriers and noncarriers in the association between the age at onset and mean diffusivity. Our results suggest that the topographical distribution of white-matter changes in AD is significantly affected by the interaction between age at onset and apoE genotype.",aged;Alzheimer disease;article;controlled study;diffusion tensor imaging;female;fractional anisotropy;frontal lobe;genetic association;genotype;human;major clinical study;male;onset age;parietal lobe;priority journal;temporal lobe;white matter,"Kim, M. J.;Seo, S. W.;Kim, S. T.;Lee, J. M.;Na, D. L.",2016,,10.1097/wad.0000000000000155,0,3353
3353,Diffusion Tensor Changes According to Age at Onset and Apolipoprotein E Genotype in Alzheimer Disease,"Age at onset is one of the most important factors that affects the clinical course in Alzheimer disease (AD), whereas other factors such as apolipoprotein E (apoE) genotype may also play a major role. In this study, we aimed to investigate the effect of age at onset and apoE genotype on white-matter changes in AD using diffusion tensor imaging. About 213 patients with AD and 66 normal individuals underwent diffusion tensor imaging, and apoE genotype was obtained in all AD patients and in 24 normal individuals. When multiple regression analysis was conducted, a younger age at onset was associated with lower fractional anisotropy in both deep-located long-range limbic and association fibers and superficial-located short-range association fibers in the frontal, the temporal, and the parietal lobes, and with a higher mean diffusivity in deep-located fibers and the bilateral medial thalamus. When analyzed separately in apoE e4 carriers and noncarriers, e4 carriers showed an association between a younger age at onset and lower fractional anisotropy, mainly in deep-located fibers, whereas noncarriers showed this association in both deep-located and superficial-located fibers. There was no difference in the spatial distribution between carriers and noncarriers in the association between the age at onset and mean diffusivity. Our results suggest that the topographical distribution of white-matter changes in AD is significantly affected by the interaction between age at onset and apoE genotype.",,"Kim, M. J.;Seo, S. W.;Kim, S. T.;Lee, J. M.;Na, D. L.",2016,May 25,10.1097/wad.0000000000000155,0,
3354,Visceral obesity is associated with white matter hyperintensity and lacunar infarct,"Background:The presence of white matter hyperintensity (WMH) and lacunar infarct are recognized as risk factors of dementia, stroke and mortality. It is undetermined whether visceral adipose tissue (VAT) area is associated with an increased risk of cerebral small vessel disease. We explored whether VAT area was responsible for cerebral small vessel disease through the identification of WMH and lacunar infarct.Subjects:A total of 2046 subjects free of cerebrovascular disease who underwent brain magnetic resonance imaging and abdominal fat computed tomography during a general health check-up were enrolled.Results:The prevalence of cerebral WMH was 37.7%. Subjects with WMH had greater VAT area and higher BMI and waist circumference than those without WMH, although significant differences in subcutaneous adipose tissue (SAT) area were not shown. Subjects with lacunar infarct also had significantly greater VAT area and higher waist circumference and BMI than those without lacunar infarct. Multivariate analyses adjusted for age, sex, diabetes, hypertension, smoking and alcohol, showed VAT area was an independent risk factor of cerebral WMH (odds ratio (OR): 1.13, 95% confidence interval (CI): 1.02-1.24, P=0.016), whereas waist circumference and SAT area were not significantly associated with the risk of WMH. Likewise, VAT area was also independently associated with lacunar infarct (OR: 1.38, 95% CI: 1.06-1.81, P=0.018), whereas the other anthropometric measures were not related with lacunar infarct.Conclusions:VAT has a significant association with cerebral small vessel disease, which was defined as WMH or lacunar infarct. Visceral obesity can be a potential therapeutic target for the prevention of cerebral small vessel disease.",C reactive protein;cholesterol;glucose;hemoglobin A1c;high density lipoprotein cholesterol;high sensitive c reactive protein;insulin;triacylglycerol;unclassified drug;abdominal fat;adult;alcohol consumption;anthropometry;article;body fat distribution;body mass;brain disease;cerebrovascular disease;computer assisted tomography;controlled study;diabetes mellitus;disease association;female;human;hypertension;intraperitoneal fat;lacunar stroke;major clinical study;male;nuclear magnetic resonance imaging;obesity;prevalence;priority journal;risk factor;subcutaneous fat;visceral obesity;waist circumference;white matter hyperintensity,"Kim, K. W.;Seo, H.;Kwak, M. S.;Kim, D.",2017,,10.1038/ijo.2017.13,0,3355
3355,Visceral obesity is associated with white matter hyperintensity and lacunar infarct,"BACKGROUND: The presence of white matter hyperintensity (WMH) and lacunar infarct are recognized as risk factors of dementia, stroke and mortality. It is undetermined whether visceral adipose tissue (VAT) area is associated with an increased risk of cerebral small vessel disease. We explored whether VAT area was responsible for cerebral small vessel disease through the identification of WMH and lacunar infarct. SUBJECTS: A total of 2046 subjects free of cerebrovascular disease who underwent brain magnetic resonance imaging and abdominal fat computed tomography during a general health check-up were enrolled. RESULTS: The prevalence of cerebral WMH was 37.7%. Subjects with WMH had greater VAT area and higher BMI and waist circumference than those without WMH, although significant differences in subcutaneous adipose tissue (SAT) area were not shown. Subjects with lacunar infarct also had significantly greater VAT area and higher waist circumference and BMI than those without lacunar infarct. Multivariate analyses adjusted for age, sex, diabetes, hypertension, smoking and alcohol, showed VAT area was an independent risk factor of cerebral WMH (odds ratio (OR): 1.13, 95% confidence interval (CI): 1.02-1.24, P=0.016), whereas waist circumference and SAT area were not significantly associated with the risk of WMH. Likewise, VAT area was also independently associated with lacunar infarct (OR: 1.38, 95% CI: 1.06-1.81, P=0.018), whereas the other anthropometric measures were not related with lacunar infarct. CONCLUSIONS: VAT has a significant association with cerebral small vessel disease, which was defined as WMH or lacunar infarct. Visceral obesity can be a potential therapeutic target for the prevention of cerebral small vessel disease.International Journal of Obesity advance online publication, 14 February 2017; doi:10.1038/ijo.2017.13.",,"Kim, K. W.;Seo, H.;Kwak, M. S.;Kim, D.",2017,Feb 14,,0,
3356,Microstructural alteration of the anterior cingulum is associated with apathy in alzheimer disease,"OBJECTIVES:: To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). Design: Cross-sectional study. Setting: University Dementia Clinic. Participants: Fifty-one very mild or mild probable AD subjects. INTERVENTION:: Volumetric magnetic resonance imaging with diffusion tensor imaging. MEASUREMENTS:: Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. Results: Apathy group showed significantly lower",,"Kim, J. W.;Lee, D. Y.;Choo, I. H.;Seo, E. H.;Kim, S. G.;Park, S. Y.;Woo, J. I.",2011,July,,0,
3357,Cerebral embolism of iodized oil (Lipiodol) after transcatheter arterial chemoembolization for hepatocellular carcinoma,"Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67-year-old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right-to-left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63-year-old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre-existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction.1,2 However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre-existing RLS. © 2009 by the American Society of Neuroimaging.",doxorubicin;gelfoam;iodinated poppyseed oil;adult;aged;article;brain cortex;brain embolism;cancer growth;cancer recurrence;case report;cerebellum cortex;chemoembolization;computer assisted tomography;Doppler echography;female;frontal lobe;heart left atrium;heart right left shunt;human;liver cell carcinoma;male;mental deterioration;middle cerebral artery;neurologic disease;transesophageal echocardiography;white matter;lipiodol,"Kim, J. T.;Heo, S. H.;Choi, S. M.;Lee, S. H.;Park, M. S.;Kim, B. C.;Kim, Y.;Kim, M. K.;Cho, K. H.",2009,,,0,
3358,Carotid artery thickening and neurocirculatory abnormalities in de novo Parkinson disease,"Cognitive dysfunction constitutes a major non-motor manifestation of Parkinson disease (PD), but the mechanisms remain incompletely understood. Neurocirculatory abnormalities such as supine hypertension (SH) and orthostatic hypotension (OH), white matter hyperintensities upon magnetic resonance imaging, and dementia are inter-related in PD, even in patients with early, levodopa-untreated disease. These abnormalities might in turn be associated with carotid atherosclerosis which, by a variety of interacting means could contribute to repeated episodes of cerebral hypo- and hyper-perfusion. We investigated inter-correlations among neurocirculatory and carotid sonographic measurements [intimal-medial thickness (IMT) and wall:lumen ratios (WLR)] in 65 patients with levodopa-untreated, de novo PD who underwent tilt table testing and 24-h ambulatory blood pressure monitoring. Increased mean IMT and WLR were associated with OH and supine and overnight blood pressures. Across individuals the orthostatic fall in systolic pressure was correlated with both IMT and WLR. Since arteriosclerosis would be expected to splint carotid sinus baroreceptors, complex positive interactions among carotid wall thickening, SH, and OH may result in myriad episodes of cerebral hypo- and hyper-perfusion, contributing to microvascular injury and consequently to the cognitive dysfunction attending PD.","Aged;Blood Pressure/physiology;Blood Pressure Monitoring, Ambulatory;Carotid Arteries/ diagnostic imaging;Circadian Rhythm;Female;Humans;Linear Models;Male;Middle Aged;Organ Size;Parkinson Disease/ diagnostic imaging/ physiopathology;Supine Position;Tilt-Table Test;Ultrasonography","Kim, J. S.;Oh, Y. S.;Lee, K. S.;Song, I. U.;Park, I. S.;Yang, D. W.;Koo, J. S.;Goldstein, D. S.",2014,Oct,,0,3359
3359,Carotid artery thickening and neurocirculatory abnormalities in de novo Parkinson disease,"Cognitive dysfunction constitutes a major non-motor manifestation of Parkinson disease (PD), but the mechanisms remain incompletely understood. Neurocirculatory abnormalities such as supine hypertension (SH) and orthostatic hypotension (OH), white matter hyperintensities upon magnetic resonance imaging, and dementia are inter-related in PD, even in patients with early, levodopa-untreated disease. These abnormalities might in turn be associated with carotid atherosclerosis which, by a variety of interacting means could contribute to repeated episodes of cerebral hypo- and hyper-perfusion. We investigated inter-correlations among neurocirculatory and carotid sonographic measurements [intimal-medial thickness (IMT) and wall:lumen ratios (WLR)] in 65 patients with levodopa-untreated, de novo PD who underwent tilt table testing and 24-h ambulatory blood pressure monitoring. Increased mean IMT and WLR were associated with OH and supine and overnight blood pressures. Across individuals the orthostatic fall in systolic pressure was correlated with both IMT and WLR. Since arteriosclerosis would be expected to splint carotid sinus baroreceptors, complex positive interactions among carotid wall thickening, SH, and OH may result in myriad episodes of cerebral hypo- and hyper-perfusion, contributing to microvascular injury and consequently to the cognitive dysfunction attending PD.",,"Kim, J. S.;Oh, Y. S.;Lee, K. S.;Song, I. U.;Park, I. S.;Yang, D. W.;Koo, J. S.;Goldstein, D. S.",1996,1,,0,
3360,Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease,"OBJECTIVE: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD. METHODS: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients. RESULTS: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia. CONCLUSIONS: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline.","Aged;Cerebrovascular Disorders/*diagnosis/epidemiology/etiology;Dementia/diagnosis/epidemiology/etiology;Female;Humans;Hypertension/diagnosis/etiology;Hypotension, Orthostatic/diagnosis/etiology;Male;Mild Cognitive Impairment/*diagnosis/epidemiology/etiology;Neuropsychological Tests;Parkinson Disease/*complications/epidemiology/*physiopathology","Kim, J. S.;Oh, Y. S.;Lee, K. S.;Kim, Y. I.;Yang, D. W.;Goldstein, D. S.",2012,Sep 25,10.1212/WNL.0b013e31826c1acd,0,
3361,The Etiologies of Early Neurological Deterioration after Thrombolysis and Risk Factors of Ischemia Progression,"Background We investigated the incidence and risk factors of early neurological worsening according to ischemia progression among acute cerebral infarction patients after intravenous thrombolysis. Methods The medical records of consecutive cerebral infarction patients treated with intravenous thrombolysis from 2 university hospitals were reviewed. Early neurological deterioration (END) was defined as 2 or more National Institutes of Health Stroke Scale aggravations within 24 hours after thrombolysis, and its etiologies were categorized by follow-up imaging into 3 groups: ischemia progression, symptomatic hemorrhage, and brain edema. We compared clinical variables between the group of patients with ischemia progression and the patients without neurological deterioration to derive etiology-specific risk factors. Results A total of 210 patients were included in this study, with 57 (26.2%) patients experiencing neurological deterioration. The prevalence of patients with END due to ischemia progression (27 patients, 12.9%) outnumbered the prevalence of patients with neurological deterioration due to symptomatic hemorrhage (n = 13) or brain edema (n = 15). Compared to the group of patients without END, the patients with ischemia progression were more likely to have a stroke subtype of large-artery atherosclerosis, to be current smokers, and to have less severe initial neurological deficits. Multivariate logistic regression analysis revealed that large-artery atherosclerosis was an independent predictor of END due to ischemia progression (odds ratio = 3.8, confidence interval = 1.6-9.3). Conclusions A major contributor to END within 24 hours after intravenous thrombolysis was ischemia progression, and the stroke subtype of large-artery atherosclerosis predicted ischemia progression.",,"Kim, J. M.;Moon, J.;Ahn, S. W.;Shin, H. W.;Jung, K. H.;Park, K. Y.",2016,1,,0,
3362,Characterization of cerebral microbleeds in idiopathic Parkinson's disease,"BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) have been extensively studied in healthy controls and patients with cerebrovascular disease and Alzheimer's disease. Our aim was to characterize the clinical and radiological features of CMBs in idiopathic Parkinson's disease (IPD). METHODS: This cross-sectional study included consecutive parkinsonian patients who attended the authors' movement disorders clinic from March 2010 to February 2012 and underwent a standard magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with a 3 T MRI machine. RESULTS: Amongst parkinsonian disorders, CMBs were most common in vascular parkinsonism (VP) (56%) and least common in IPD (17.7%). In IPD, CMBs were significantly associated with white matter hyperintensities and concurrent lacunar infarctions. The presence of CMBs had no effect on various cognitive domains in IPD. IPD with CMBs was discriminated from VP by clinical and neuroimaging findings: frequencies of motor subtypes were similar between IPD with and without CMBs, whereas all VP patients were the postural-instability gait difficulty type. In 90.9% of the IPD cases with CMBs, the numbers of CMBs were three or less, whereas the numbers of CMBs exceeded three in 50% of the cases of VP and exceeded 10 in 31.3% of the cases (P < 0.001). The topography of the CMBs in IPD was also different from that in VP (P < 0.01). CONCLUSIONS: Cerebral microbleeds are not rare in IPD, and IPD with CMBs does not appear to be a form of VP. Further studies in larger populations are needed to elucidate the clinical implications of CMBs in terms of prognoses and cognitive changes in IPD.","Aged;Aged, 80 and over;Cerebral Hemorrhage/etiology/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Parkinson Disease/complications/ pathology;White Matter/ pathology","Kim, J. H.;Park, J.;Kim, Y. H.;Ma, H. I.;Kim, Y. J.",2015,Feb,10.1111/ene.12584,0,
3363,Extensive white matter injury in hypoglycemic coma,,aged;article;blood examination;brain injury;case report;diffusion weighted imaging;female;hospital admission;human;hypoglycemic coma;mental deterioration;nuclear magnetic resonance imaging;priority journal;septicemia;vital sign;white matter;white matter injury,"Kim, J. H.;Koh, S. B.",2007,,,0,
3364,"Regional white matter hyperintensities in normal aging, single domain amnestic mild cognitive impairment, and mild Alzheimer's disease","Few studies have examined white matter hyperintensities (WMH) along the cognitive continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and Alzheimer's disease (AD). The aims of our study were to explore relationships between the extent and location of WMH and disease severity along the cognitive continuum and to determine whether differences in the distribution of WMH could be predictive of specific patterns of cognitive impairment. We compared cognitive function, vascular risk factors, and regional (frontal lobe, parieto-occipital [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24 age-matched and education-matched normal controls. A quantitative volumetric method was applied to measure WMH burden. Total and regional WMH burdens, except for those in the temporal lobe, were significantly correlated with age (p<0.01). We found a trend toward increasing WMH volume with disease severity, higher in AD than in sd-aMCI and lowest in the controls. Total WMH volume was associated with the global cognitive test score. In multiple linear regression analysis, PV WMH volume, but not deep WMH volume, strongly predicted performances on the Controlled Oral Word Association test and the Color Word Stroop test after adjusting for important demographic variables. Only PO WMH volume was a significant predictor of a cognitive test score when frontal and temporal WMH volumes were simultaneously entered into the regression model. The extent and distribution of WMH, especially in the PV and PO regions, were associated with disease severity and reduced cognition.","Aged;Aging/*pathology;Alzheimer Disease/*pathology;Amnesia/complications/*pathology;Brain/*pathology;Chi-Square Distribution;Cognition Disorders/complications/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Statistics as Topic","Kim, J. H.;Hwang, K. J.;Kim, J. H.;Lee, Y. H.;Rhee, H. Y.;Park, K. C.",2011,Aug,10.1016/j.jocn.2011.01.008,0,
3365,Incidence and predictors of silent embolic cerebral infarction following diagnostic coronary angiography,"BACKGROUND: Coronary angiography (CAG) is an invasive diagnostic procedure, which could lead to procedure related complications. One of the well known post-procedural complications is cerebral embolic infarction with or without symptoms. Silent embolic cerebral infarction (SECI) has clinical significance because it can progress to a decline in cognitive function and increase the risk of dementia in the long term. The aim of this study was to detect the incidence and predictors of SECI after diagnostic CAG using diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: A total of 197 patients with coronary artery disease who underwent DW-MRI for evaluation of intracranial vasculopathy before coronary artery bypass graft surgery were retrospectively enrolled in the present study. DW-MRI was performed within 48 h after diagnostic CAG. SECI was diagnosed as presence of focal bright high signal intensity in DW-MRI. Patients were divided into groups according to presence/absence of SECI (+ SECI vs. - SECI, respectively). The clinical and angiographic characteristics were analyzed and independent predictors were evaluated. RESULTS: Of the 197 patients, SECI occurred in 20 patients (10.2%) after diagnostic CAG. Age, female gender, frequency of underlying atrial fibrillation, extent of coronary disease, and fluoroscopic time during diagnostic CAG were not different between the + SECI and - SECI groups. Left ventricular ejection fraction was significantly lower in the + SECI group than in the - SECI group (45.9 +/- 8.5% vs. 51.4 +/- 13.1%, p=0.014) and performance rate of internal mammary artery (IMA) angiography was significantly higher in the + SECI group compared with the - SECI group (85% vs. 37.2%, p<0.001). By multivariate analysis, performing IMA angiography was the only predictor of SECI (OR=14.642; 95% CI=3.201 to 66.980, p=0.001). CONCLUSIONS: The incidence of SECI after diagnostic CAG was not infrequent. Diagnostic CAG with IMA angiography may increase the risk of SECI.",Aged;Asymptomatic Diseases/ epidemiology;Cerebral Infarction/ epidemiology/pathology;Coronary Angiography/ adverse effects/ statistics & numerical data;Coronary Artery Disease/ radiography;Diffusion Magnetic Resonance Imaging;Female;Humans;Incidence;Intracranial Embolism/ epidemiology/pathology;Male;Middle Aged;Multivariate Analysis;Predictive Value of Tests;Retrospective Studies,"Kim, I. C.;Hur, S. H.;Park, N. H.;Jun, D. H.;Cho, Y. K.;Nam, C. W.;Kim, H.;Han, S. W.;Choi, S. Y.;Kim, Y. N.;Kim, K. B.",2011,Apr 14,10.1016/j.ijcard.2009.10.053,0,
3366,"Effects of APOE ε4 on brain amyloid, lacunar infarcts, and white matter lesions: Astudy among patients with subcortical vascular cognitive impairment","The relationship between the apolipoprotein E ε4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer's disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(-) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79-2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70-11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54-7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease. © 2013 Elsevier Inc.",amyloid beta protein;apolipoprotein E4;Pittsburgh compound B;aged;Alzheimer disease;article;brain region;brain size;cognitive defect;cohort analysis;controlled study;female;gene frequency;genetic association;genotype;high risk population;human;lacunar stroke;major clinical study;male;nuclear magnetic resonance imaging;positron emission tomography;priority journal;prospective study;protein metabolism;subcortical vascular cognitive impairment;white matter lesion,"Kim, H. J.;Ye, B. S.;Yoon, C. W.;Cho, H.;Noh, Y.;Kim, G. H.;Choi, Y. S.;Kim, J. H.;Jeon, S.;Lee, J. M.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, C.;Kang, D. R.;Ki, C. S.;Lee, J. H.;Werring, D. J.;Weiner, M. W.;Na, D. L.;Seo, S. W.",2013,,,0,
3367,"Effects of APOE epsilon4 on brain amyloid, lacunar infarcts, and white matter lesions: a study among patients with subcortical vascular cognitive impairment","The relationship between the apolipoprotein E epsilon4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer's disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(-) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79-2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70-11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54-7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.","Aged;Aged, 80 and over;Alzheimer Disease/complications;Amyloid beta-Peptides/*metabolism;Aniline Compounds;Apolipoprotein E4/genetics/*metabolism;Brain/*metabolism/pathology/radionuclide imaging;Cognition Disorders/complications/*pathology;Female;Genotype;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Prospective Studies;Thiazoles;Vascular Diseases/complications/*pathology;Apoe;Amyloid beta burden;Lacune;Subcortical vascular cognitive impairment;White matter hyperintensity","Kim, H. J.;Ye, B. S.;Yoon, C. W.;Cho, H.;Noh, Y.;Kim, G. H.;Choi, Y. S.;Kim, J. H.;Jeon, S.;Lee, J. M.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, C.;Kang, D. R.;Ki, C. S.;Lee, J. H.;Werring, D. J.;Weiner, M. W.;Na, D. L.;Seo, S. W.",2013,Nov,10.1016/j.neurobiolaging.2013.05.009,0,
3368,"Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories","See Cohen (doi:10.1093/aww183) for a scientific commentary on this article. Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.",amyloid beta protein;biological marker;Pittsburgh compound B;adult;aged;article;brain infarction;cognitive defect;color vision test;cortical thickness (brain);diffusion tensor imaging;disease association;executive function;female;follow up;human;lacune;longitudinal study;major clinical study;male;memory test;mental deterioration;multimodal imaging;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;positron emission tomography;priority journal;prospective study;radioactivity;visual memory,"Kim, H. J.;Yang, J. J.;Kwon, H.;Kim, C.;Lee, J. M.;Chun, P.;Kim, Y. J.;Jung, N. Y.;Chin, J.;Kim, S.;Woo, S. Y.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, J. S.;Lee, J. H.;Weiner, M. W.;Na, D. L.;Seo, S. W.",2016,,10.1093/brain/aww148,0,
3369,Structural explanation of poor prognosis of amyotrophic lateral sclerosis in the non-demented state,"BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS), a motor neuron disease, is associated with various cortical symptoms including mild cognitive decline with behavior changes, suggesting the involvement of extra-motor areas in ALS. Our aim was to investigate the specific patterns of brain atrophy in sporadic, impaired ALS patients without commonly known genetic mutations using voxel-based morphometry. MATERIALS AND METHODS: Forty-seven patients with sporadic ALS and 28 age-matched healthy controls were recruited. ALS participants were divided into three groups according to comprehensive neuropsychological testing: pure (ALS-pure), cognitive impairment (ALSci) and behavioral impairment (ALSbi). Quantitative comparison of brain atrophy patterns was performed amongst these three groups using voxel-based analysis. All analyses were adjusted for total intracranial volume, age, sex, disease duration and functional disability score. RESULTS: The ALSci group exhibited decreased volume in the left cerebellum, fusiform gyrus, optic radiations and corticospinal tracts compared to healthy controls. ALSci patient imaging showed decreased brain volume in the bilateral cerebellum, right putamen gray matter and bilateral superior longitudinal fasciculi white matter compared to pure ALS patients (P < 0.001 uncorrected, corrected for the entire volume). Compared to healthy controls, ALS-pure and ALSbi groups did not show any significant volume changes in gray and white matter. CONCLUSIONS: These findings also support the hypothesis that ALS pathogenesis has a dual focality of onset (cortex and anterior horn) with contiguous spread outwards. Additionally, neuropsychological features may be an important predictor of progression and survival rates in ALS.",amyotrophic lateral sclerosis;atrophy;cognitive impairment;voxel-based morphometry,"Kim, H. J.;Oh, S. I.;de Leon, M.;Wang, X.;Oh, K. W.;Park, J. S.;Deshpande, A.;Buj, M.;Kim, S. H.",2017,Jan,,0,
3370,Differential cholinergic pathway involvement in Alzheimer's disease and subcortical ischemic vascular dementia,"BACKGROUND: This study aimed to evaluate the relationship between loss of white matter cholinergic pathways, atrophy of the nucleus basalis of Meynert (NBM), and cognitive function in patients with subcortical ischemic vascular dementia (SIVD) or Alzheimer's disease (AD). METHODS: The participants included 26 SIVD, 17 probable AD with or without white-matter changes, and 20 age-matched healthy controls. Thin-section coronal T2-weighted images were acquired using 3.0 T MR. The extent of white matter hyperintensities within cholinergic pathways were assessed using the cholinergic pathways hyperintensities scale (CHIPS). NBM atrophy was assessed from the thickness of the substantia innominata (SI) at the level of the crossing of the anterior commissure. Cognitive impairment was measured using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Correlations between CHIPSs, SI thickness, and cognitive impairment were evaluated using the Spearman ranked correlation test. RESULTS: In AD, MMSE scores and CDR were correlated with SI thickness (rho = 0.450, p = 0.006 and rho = -0.520, p = 0.030, respectively) but not with CHIPS scores (rho = -0.160, p = 0.530 and rho = 0.270, p = 0.292, respectively). By contrast, aggravated MMSE score and CDR in SIVD had a tendency to correlate with elevated CHIPS scores (rho = -0.344, p = 0.127 and rho = 0.521, p = 0.021, respectively) but not with SI thickness (rho = -0.210, p = 0.480 and rho = 0.080, p = 0.736, respectively). CONCLUSIONS: Loss of cholinergic pathways correlates with cognitive dysfunction in both AD and SIVD. The mechanisms appear to differ: NBM atrophy is likely to be the predominant contributor to cognitive impairments in AD, whereas, the cognitive dysfunction of SIVD was associated with compromised subcortical cholinergic fibers not with nucleus itself.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/epidemiology;Brain Ischemia/ diagnosis/epidemiology;Cholinergic Neurons/ pathology;Dementia, Vascular/ diagnosis/epidemiology;Female;Humans;Male;Neural Pathways/pathology;Prospective Studies","Kim, H. J.;Moon, W. J.;Han, S. H.",2013,,10.3233/jad-122320,0,
3371,Amyotrophic lateral sclerosis and frontotemporal lobar degeneration in association with CADASIL,"Amyotrophic lateral sclerosis (ALS) can present with heterogeneous symptoms resulting from the involvement of multiple brain systems including extramotor cortical areas. Involvement of other brain areas can cause diverse clinical symptoms including cognitive impairment and extrapyramidal symptoms. We report the case of a 50-year-old woman with bulbar onset ALS and frontotemporal lobar degeneration (FTLD), confirmed as cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The patient and her first-degree relatives harbored a mutation (R75P) in the NOTCH3 gene, indicative of vascular deficits. The details of this case add plausibility to the idea that ALS, FTLD, and CADASIL are different aspects of a spectrum of disorders with overlapping pathologic mechanisms. © 2012 Lippincott Williams & Wilkins, Inc.",Notch3 receptor;TAR DNA binding protein;adult;amyotrophic lateral sclerosis;arm weakness;article;behavior change;CADASIL;case report;disease association;family history;female;frontotemporal dementia;gene deletion;gene mutation;general condition deterioration;genetic analysis;human;joint function;Mini Mental State Examination;motor neuron disease;neurologic examination;nuclear magnetic resonance imaging;priority journal;tendon reflex;verbal behavior;visual memory,"Kim, H. J.;Kim, H. Y.;Ki Paek, W.;Park, A.;Young Park, M.;Seok Ki, C.;Park, H. M.;Kim, S. H.",2012,,,0,
3372,The effects of small vessel disease and amyloid burden on neuropsychiatric symptoms: a study among patients with subcortical vascular cognitive impairments,"Neuropsychiatric symptoms (NPS) affect the quality of life of patients with dementia and increase the burden on caregivers. We aimed to evaluate how small vessel disease (SVD) such as lacunae or white matter hyperintensities (WMH), and amyloid burden affect NPS. We recruited 127 patients with subcortical vascular cognitive impairment who were assessed with brain magnetic resonance imaging, Pittsburgh compound-B (PiB) positron emission tomography and the neuropsychiatric inventory (NPI). To explore the association between lacunae, WMH, or PiB retention ratio and NPS, we performed multivariate regression analysis after controlling for possible confounders. Each additional lacuna, especially in the frontal region, was associated with higher odds of depression, apathy, aberrant motor behavior, nighttime behavior, appetite changes, and higher score of total NPI; larger WMH volume, especially in the frontal region, was associated with higher odds of apathy and higher score of total NPI. Furthermore, for the effects of lacunae or WMH on total NPI score we set Clinical Dementia Rating Sum of Boxes as the mediator. Greater PiB retention ratio was associated with higher odds of delusions and irritability. The SVD and amyloid pathologies did not show interactive effects on NPS. Our findings suggested that SVD and amyloid burden independently affected specific NPS.","Aged;Aged, 80 and over;Dementia, Vascular/ diagnosis/ psychology;Female;Humans;Male;Microvessels/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Plaque, Amyloid/ diagnosis/ psychology;Prospective Studies","Kim, H. J.;Kang, S. J.;Kim, C.;Kim, G. H.;Jeon, S.;Lee, J. M.;Oh, S. J.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Noh, Y.;Cho, H.;Yoon, C. W.;Chin, J.;Cummings, J. L.;Lee, J. H.;Na, D. L.;Seo, S. W.",2013,Jul,10.1016/j.neurobiolaging.2013.01.002,0,
3373,Effects of amyloid and small vessel disease on white matter network disruption,"There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/pathology/radionuclide imaging;Amyloid/ metabolism;Aniline Compounds;Brain/metabolism/ pathology/radionuclide imaging;Cognition Disorders/metabolism/pathology/radionuclide imaging;Dementia, Vascular/ metabolism/ pathology/radionuclide imaging;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neural Networks (Computer);Neural Pathways/metabolism/pathology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography;Thiazoles;White Matter/metabolism/ pathology/radionuclide imaging","Kim, H. J.;Im, K.;Kwon, H.;Lee, J. M.;Ye, B. S.;Kim, Y. J.;Cho, H.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, J. S.;Lee, J. H.;Na, D. L.;Seo, S. W.",2015,,10.3233/jad-141623,0,
3374,Clinical effect of white matter network disruption related to amyloid and small vessel disease,"Background: We tested our hypothesis that the white matter network might mediate the effect of amyloid and small vessel disease (SVD) on cortical thickness and/or cognition. Methods: We prospectively recruited 232 patients with cognitive impairment. Amyloid was assessed using Pittsburgh compound B-PET. SVD was quantified as white matter hyperintensity volume and lacune number. The regional white matter network connectivity was measured as regional nodal efficiency by applying graph theoretical analysis to diffusion tensor imaging data. We measured cortical thickness and performed neuropsychological tests. Results: SVD burden was associated with decreased nodal efficiency in the bilateral frontal, lateral temporal, lateral parietal, and occipital regions. Path analyses showed that the frontal nodal efficiency mediated the effect of SVD on the frontal atrophy and frontal-executive dysfunction. The temporoparietal nodal efficiency mediated the effect of SVD on the temporoparietal atrophy and memory dysfunction. However, Pittsburgh compound B retention ratio affected cortical atrophy and cognitive impairment without being mediated by nodal efficiency. Conclusions: We suggest that a disrupted white matter network mediates the effect of SVD, but not amyloid, on specific patterns of cortical atrophy and/or cognitive impairment. Therefore, our findings provide insight to better understand how amyloid and SVD burden can give rise to brain atrophy or cognitive impairment in specific patterns.",,"Kim, H. J.;Im, K.;Kwon, H.;Lee, J. M.;Kim, C.;Kim, Y. J.;Jung, N. Y.;Cho, H.;Ye, B. S.;Noh, Y.;Kim, G. H.;Ko, E. D.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Lee, J. H.;Ewers, M.;Weiner, M. W.;Na, D. L.;Seo, S. W.",2015,7,,0,
3375,"Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients","BACKGROUND: Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. OBJECTIVE: The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. METHODS: In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. RESULTS: When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. CONCLUSIONS: Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.",Alzheimer's disease;amyloid;central executive network;default mode network;resting-state functional MRI;small vessel disease;subcortical vascular dementia,"Kim, H. J.;Cha, J.;Lee, J. M.;Shin, J. S.;Jung, N. Y.;Kim, Y. J.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, J. S.;Lee, J. H.;Na, D. L.;Seo, S. W.",2016,Jan 12,10.3233/jad-150637,0,
3376,Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population,"STUDY OBJECTIVE: Obstructive sleep apnea (OSA) contributes to the development of systemic hypertension, and hypertension strongly predicts the development of white matter change (WMC). Thus, it is plausible that OSA mediates WMC. The goal of the current study is to determine whether a contextual relationship exists between OSA and cerebral WMC. DESIGN: Cross-sectional analyses conducted in a population-based study. SETTING: Korean community-based sample from the Korean Genome and Epidemiology Study (KoGES) who attended examinations in 2011 at a medical center. PARTICIPANTS: There were 503 individuals (mean +/- SD, age 59.63 +/- 7.48 y) who were free of previously diagnosed cardiovascular and neurologic diseases. MEASUREMENTS AND RESULTS: Participants underwent 1-night polysomnography and were classified as no OSA (obstructive apnea-hypopnea index [AHI] < 5, n = 289), mild OSA (AHI 5-15, n = 161), and moderate to severe OSA (AHI >/= 15, n = 53). WMC was identified with brain magnetic resonance imaging (MRI) and was found in 199 individuals (39.56%). Multivariate logistic regression analyses adjusted for covariates revealed that moderate to severe OSA was significantly associated with the presence of WMC (odds ratio [OR] 2.08, 95%, confidence interval [CI] 1.05-4.13) compared with no OSA. Additional adjustment of hypertension to the model did not alter the significance of the association (OR 2.03, 95% CI 1.02-4.05). CONCLUSIONS: Moderate to severe OSA is an independent risk factor for WMC in middle-aged and older individuals. Thus, early recognition and treatment of OSA could reduce the risk of stroke and vascular dementia.","Age Factors;Aged;Brain/ pathology;Cohort Studies;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Polysomnography;Republic of Korea;Risk Factors;Severity of Illness Index;Sleep Apnea, Obstructive/ complications/ pathology","Kim, H.;Yun, C. H.;Thomas, R. J.;Lee, S. H.;Seo, H. S.;Cho, E. R.;Lee, S. K.;Yoon, D. W.;Suh, S.;Shin, C.",2013,May,10.5665/sleep.2632,0,
3377,The neural correlates of motor intentional disorders in patients with subcortical vascular cognitive impairment,"Subcortical vascular cognitive impairment (SVCI) refers to cognitive impairment associated with small vessel disease. Motor intentional disorders (MID) have been reported in patients with SVCI. However, there are no studies exploring the neuroanatomical regions related to MID in SVCI patients. The aim of this study, therefore, was to investigate the neural correlates of MID in SVCI patients. Thirty-one patients with SVCI as well as 10 healthy match control participants were included. A “Pinch-Grip” apparatus was used to quantify the force control capabilities of the index finger in four different movement phases including initiation, development, maintenance, and termination. All participants underwent magnetic resonance imaging (MRI). Topographical cortical areas and white matter tracts correlated with the performances of the four different movement phases were assessed by the surface-based morphometry and tract-based spatial statistics analyses. Poorer performance in the maintenance task was related to cortical thinning in bilateral dorsolateral prefrontal, orbitofrontal and parietal cortices, while poorer performance in the termination task was associated with the disruption of fronto-parietal cortical areas as well as the white matter tracts including splenium and association fibers such as superior longitudinal fasciculus. Our study demonstrates that cortical areas and underlying white matter tracts associated with fronto-parietal attentional system play an important role in motor impersistence and perseveration in SVCI patients.",,"Kim, G. H.;Seo, S. W.;Jung, K.;Kwon, O. H.;Kwon, H.;Kim, J. H.;Roh, J. H.;Kim, M. J.;Lee, B. H.;Yoon, D. S.;Hwang, J. W.;Lee, J. M.;Jeong, J. H.;You, H.;Heilman, K. M.;Na, D. L.",2016,1,,0,
3378,Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI variables,"OBJECTIVE: The purpose of this study was to propose new criteria for differentiating Pittsburgh compound B (PiB)-negative from PiB-positive subcortical vascular dementia (SVaD) using clinical and MRI variables. METHODS: We measured brain amyloid deposition using PiB-PET in 77 patients with SVaD. All patients met DSM-IV criteria for vascular dementia and had severe white matter hyperintensities on MRI, defined as a cap or band >/= 10 mm as well as a deep white matter lesion >/= 25 mm. Eleven models were considered to differentiate PiB(-) from PiB(+) SVaD using 4 variables, including age, number of lacunes, medial temporal atrophy (MTA), and APOE epsilon4. The ideal cutoff values in each of the 11 models were selected using the highest Youden index. RESULTS: A total of 49 of 77 patients (63.6%) tested negative for PiB retention, while 28 (36.4%) tested positive for PiB retention. The ideal model for differentiating PiB(-) from PiB(+) SVaD was as follows: age </= 75 years, >/= 5 lacunes, and MTA </= 3, which together yielded an accuracy of 67.5%. CONCLUSION: When patients meet the DSM-IV criteria for vascular dementia and also have severe white matter hyperintensities, younger age, greater number of lacunes, and lesser MTA, these are predictive of a PiB(-) scan in patients with SVaD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the combination of younger age, greater number of lacunes, and lesser MTA identifies patients with SVaD at lower risk of Alzheimer disease pathology.","Aged;Aged, 80 and over;Area Under Curve;Atrophy/diagnosis/etiology;Brain/*pathology/*radionuclide imaging;Dementia, Vascular/complications/*diagnosis;Female;Humans;Intracranial Hemorrhages/diagnosis/etiology;Leukoencephalopathies/diagnosis/etiology;*Magnetic Resonance Imaging/methods/standards;Male;Outcome Assessment (Health Care)/methods/standards;Positron-Emission Tomography;Prospective Studies;Psychiatric Status Rating Scales;Republic of Korea;Stroke, Lacunar/diagnosis/etiology;Vision Disorders/diagnosis/etiology","Kim, G. H.;Lee, J. H.;Seo, S. W.;Ye, B. S.;Cho, H.;Kim, H. J.;Noh, Y.;Yoon, C. W.;Chin, J. H.;Oh, S. J.;Kim, J. S.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Jeong, J. H.;Na, D. L.",2014,Apr 29,10.1212/wnl.0000000000000360,0,
3379,A case of disseminated polycystic dilated perivascular spaces presenting with dementia and parkinsonism,"The perivascular spaces (PVSs) of the brain are lined with pia and contain interstitial fluid. In general, PVSs are small, asymptomatic, and identifiable at all ages. When PVSs are significantly enlarged, they can produce various clinical manifestations such as headache and dizziness. A 67-year-old man was admitted with cognitive impairment and gait disturbance with a 5-month history. Brain MRI showed multiple cystic PVSs in periventricular and subcortical white matter of both hemispheres. Medication with dopaminergic agents produced a moderate clinical improvement, while anticholinesterase was not effective. This case suggests that disseminated polycystic dilated PVSs may present with dementia and Parkinsonism.",Dementia;Parkinsonism;Perivascular space,"Kim, D. G.;Oh, S. H.;Kim, O. J.",2007,Jun,10.3988/jcn.2007.3.2.96,0,
3380,Reliability of two-dimensional and three-dimensional pseudo-continuous arterial spin labeling perfusion MRI in elderly populations: Comparison with 15o-water positron emission tomography,"Purpose To investigate the reliability and accuracy of two pseudo-continuous arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient-echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the readout, respectively. Materials and Methods Each sequence was performed twice 4 weeks apart on six normal control subjects, six elderly subjects with mild cognitive impairment (MCI), and one participant with Alzheimer's disease (AD). Eight of these subjects also underwent H <sub>2</sub><sup>15</sup>O positron emission tomography (PET) scans on the same day or proximal to their second MRI scan. The longitudinal repeatability of EPI and GRASE pCASL were evaluated with the intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Results The ICCs of global perfusion measurements were 0.697 and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also demonstrated a higher longitudinal repeatability for regional perfusion measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL showed a higher degree of spatial correlation with PET than GRASE pCASL, although the difference was not statistically significant. Conclusion The 3D GRASE pCASL offers better repeatability than 2D EPI pCASL, thereby may provide a reliable imaging marker for the evaluation of disease progression and treatment effects in MCI and early AD subjects. 2013 Wiley Periodicals, Inc.",accuracy;adult;aged;Alzheimer disease;article;brain blood flow;brain perfusion;brain region;clinical article;Clinical Dementia Rating;controlled clinical trial;controlled study;correlation coefficient;echo planar imaging;female;gray matter;human;intermethod comparison;male;middle aged;mild cognitive impairment;Mini Mental State Examination;nuclear magnetic resonance scanner;perfusion weighted imaging;positron emission tomography;priority journal;pseudo continuous arterial spin labeling perfusion weighted imaging;regional perfusion;sample size;test retest reliability;three dimensional gradient and spin echo;three dimensional imaging;two dimensional gradient echo planar imaging;white matter;oxygen 15;water,"Kilroy, E.;Apostolova, L.;Liu, C.;Yan, L.;Ringman, J.;Wang, D. J. J.",2014,,10.1002/jmri.24246,0,
3381,An assessment of the role of 123I-N-isopropyl-p-iodoamphetamine with single-photon emission computed tomography in the diagnosis of stroke and Alzheimer's disease,"The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92% to 100%) than computerized tomography (55% to 86%) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69%. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50% to 100%, while specificity has ranged from 97% to 100%. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.","Alzheimer Disease/ radionuclide imaging;Amphetamines;Cerebrovascular Disorders/ radionuclide imaging;Humans;Iodine Radioisotopes;Iofetamine;Meta-Analysis as Topic;Sensitivity and Specificity;Tomography, Emission-Computed","Killen, A. R.;Oster, G.;Colditz, G. A.",1989,Apr,,0,
3382,A case of fucosidosis type ii: Diagnosed with dysmorphological and radiological findings,"Fucosidosis is a rare autosomal recessive lysosomal storage disorder in which fucose-containing glycolipids, glycoproteins and oligosaccharides accumulate in tissues, as a result of a deficiency of α-L-fucosidase. In this report we describe clinical, dysmorphological and radiological findings of a boy with this disorder. Developmental delay, skeletal deformities and mild coarsening of the face began at two years of age. Clinical signs typical for fucosidosis evolved over time. Psychomotor deterioration progressed slowly. At age 12, he could not walk without help; he was admitted to the hospital with intellectual disability, short stature and coarse facial features. A skeletal survey showed dysostosis multiplex. Cranial MRI demonstrated high intensities on the periventricular white matter and low intensities on the basal ganglia on T2- weighted images. Despite the absence of angiokeratoma on the skin, type II fucosidosis with clinical, dysmorphological and radiological signs was suspected. The diagnosis was established on the basis of severely decreased activity of α-L-fucosidase in the leukocytes. The natural history and specific dysmorphic and radiological findings should, even in the absence of angiokeratoma, assist in the differential diagnosis of this rare condition when lysosomal storage disorders are suspected, particularly in populations in which consanguineous marriages are common.",,"Kılıç, E.;Kılıç, M.;Eda Ütine, G.;Sivri, S.;Coskun, T.;Alanay, Y.",2014,2014,,0,
3383,Prevalence of CADASIL and fabry disease in a cohort of MRI defined younger onset Lacunar Stroke,"Background and Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopa-thy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. Methods Caucasian patients with lacunar infarction, aged <70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI's and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. Results Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade >2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1 %) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. Conclusion CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected.",Notch3 receptor;osteocalcin;adult;aged;article;CADASIL;Caucasian;cohort analysis;Fabry disease;female;gain of function mutation;gene;genetic association;GLA gene;human;lacunar stroke;leukoaraiosis;loss of function mutation;major clinical study;male;middle aged;missense mutation;NOTCH3 gene;nuclear magnetic resonance imaging;onset age;prevalence,"Kilarski, L. L.;Rutten-Jacobs, L. C. A.;Bevan, S.;Baker, R.;Hassan, A.;Hughes, D. A.;Markus, H. S.;Kaya, N.;Monaghan, J.;Zanich, A.;Febrey, S.;Smith, E.;Lennon, J.;Baron, J. C.;Warburton, E.;Day, D. J.;White, J.;Rashed, K.;Muir, K.;Smith, W.;Lees, K. R.;Dawson, J.;Guyler, P.;Brown, M.;Blight, A.;Pasco, K.;Chatterjee, K.;Baht, H.;Gunathilagan, G.;James, M.;Collas, D.;Briley, D.;Burn, M.;Kelly, D.;Durairaj, R.;Punekar, S.;Bath, P.;Hammonds, F.;Kalra, L.;Sekaran, L.;Sethuraman, S.;Justin, F.;Molloy, J.;Wilcock, D.;Jenkinson, D.;White, R.;Rudd, T.;Lawrence, E.;Rajkumar, C.;Breeds, J.;Giallombardo, E.;Dellafera, D.;Macleod, M.;Sharma, P.;Ford, G.;Sudlow, C.;O'Donnell, M.;Harrington, F.;Courtauld, G.;Dutta, D.;Jones, V.;Robinson, T.;Mistri, A.;Hussain, M.;Manoj, A.;Caine, S.;Dent, M.;Williams, R.;Clarke, B.;Shaw, L.;Madigan, B.;Price, C.;Orugun, O.;Glover, R.;Sanmuganathan, S.;MacWalter, R.;Cassidy, T.;Bokhari, M.;Rothwell, P.;Mawer, S.;Punnoose, S.;Sajid, M.;Nor, A. M.;Athulathmudali, C.;Namushi, R.;Krishnamoorthy, S.;Albazzaz, M.;Torane, P.;Elliott, K.;Hawley, K.;Maskell, P.;Gompertz, P.;Johnston, S.;Patterson, C.;Baldwin, N.;Harrison, P.;Duodu, Y.;Owusu-Agyei, P.;Okwera, J.;Venables, G.;Durward, G.;Majumdar, N.;Coyle, J.",2015,,,0,
3384,Frontal lobe atrophy in motor neuron diseases,"Neuronal degeneration in the precentral gyrus alone cannot account for the occurrence of spastic paresis in motor neuron diseases. To look for more extensive cortical atrophy we measured MRIs of the upper parts of the frontal and parietal lobes in 11 sporadic cases of classical amyotrophic lateral sclerosis (ALS) eight patients with primary lateral sclerosis (PLS) and an age- and sex-matched group of 49 neurologically normal people. None of the patients had overt dementia or other mental diseases. In PLS there is progressive spastic paresis but in contrast to ALS there is no lower motor neuron degeneration. The surface area of the precental al gyri and the amount of underlying white matter in PLS were consistently ~75% of the normal size. By contrast there was some shrinkage of the precentral gyri in some of the ALS patients but the mean measurements for the group did not differ significantly from the controls. Anterior to the precentral sulci. the cortical surface area in PLS was ~85% of that of the controls with correspondingly reduced white matter. In ALS the cortical surface areas of the anterior frontal lobes did not differ from those of the controls but the amount of underlying white matter was reduced almost as much in ALS as it was in PLS. The measured changes in the frontal lobes suggest that in PLS there is simultaneous atrophy of the primary, premotor and supplementary motor areas of the cortex, with consequent degeneration of corticospinal and corticoreticular axons descending through the underlying white matter. These changes could account for the progressive upper motor neuron syndrome. In ALS, with no significant frontal cortical atrophy, the shrinkage of the white matter may be due to degeneration of axons projecting to the frontal cortex from elsewhere. Deprivation of afferents could explain the diminution of motor functions of the frontal lobes in ALS and also the changes in word fluency, judgement and attention that can be detected by appropriate testing in some patients with the disease. Incidental observations include slightly larger parietal lobes but no difference in the frontal lobes in men as compared with women. There was also a small but significant decrease in size of the normal frontal lobes with age. The latter change was much smaller than the atrophy seen in patients with ALS and PLS.",adult;aged;amyotrophic lateral sclerosis;article;attention;brain atrophy;controlled study;decision making;dementia;female;frontal lobe;human;major clinical study;male;mental disease;motoneuron;motor cortex;motor neuron disease;motor performance;nerve cell degeneration;nerve fiber;nuclear magnetic resonance imaging;parietal lobe;priority journal;pyramidal tract;sensory nerve;spastic paresis;white matter,"Kiernan, J. A.;Hudson, A. J.",1994,,,0,
3385,Magnetic resonance imaging findings in HIV cognitive impairment,"Atrophy and white matter changes seen on magnetic resonance imaging scans have been observed in association with the acquired immunodeficiency syndrome dementia complex, but these appear to be late findings relative to clinical expression. We report a new magnetic resonance imaging observation in patients with early cognitive impairment due to human immunodeficiency virus infection. Fifty-two patients had a total of 86 magnetic resonance imaging scans during the study period. All scans were obtained with a 1.5-T system. The proton density spin echo (repetition time of 2000 milliseconds and echo delay time of 30 milliseconds) study demonstrated high-signal lesions in the region of the splenium of the corpus callosum and in the crura of the fornices. The lesions demonstrated no contrast enhancement with gadopentate dimeglumine. Pathological examination was performed in five patients. The fornix-subcallosal abnormality may be related to the memory dysfunction in patients with human immunodeficiency virus-related cognitive impairment.",Adult;Brain/ pathology;Cognition;Dementia/ complications;Female;HIV Infections/pathology/ psychology;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Kieburtz, K. D.;Ketonen, L.;Zettelmaier, A. E.;Kido, D.;Caine, E. D.;Simon, J. H.",1990,Jun,,0,
3386,Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education,"We determined topographic selectivity and diagnostic utility of brain atrophy in probable Alzheimer's disease (AD) and correlations with demographic factors such as age, sex, and education. Computerized imaging analysis techniques were applied to MR images in 32 patients with probable AD and 20 age- and sex-matched normal control subjects using tissue segmentation and three-dimensional surface rendering to obtain individualized lobar volumes, corrected for head size by a residualization technique. Group differences emerged in gray and white matter compartments particularly in parietal and temporal lobes. Logistic regression demonstrated that larger parietal and temporal ventricular CSF compartments and smaller temporal gray matter predicted AD group membership with an area under the receiver operating characteristic curve of 0.92. On multiple regression analysis using age, sex, education, duration, and severity of cognitive decline to predict regional atrophy in the AD subjects, sex consistently entered the model for the frontal, temporal, and parietal ventricular compartments. In the parietal region, for example, sex accounted for 27% of the variance in the parietal CSF compartment and years of education accounted for an additional 15%, with women showing less ventricular enlargement and individuals with more years of education showing more ventricular enlargement in this region. Topographic selectivity of atrophic changes can be detected using quantitative volumetry and can differentiate AD from normal aging. Differential effects of sex and years of education can also be detected by these methods. Quantification of tissue volumes in vulnerable regions offers the potential for monitoring longitudinal change in response to treatment.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Atrophy;Brain/pathology;Diagnosis, Computer-Assisted;Education;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Reference Values;Sex Characteristics","Kidron, D.;Black, S. E.;Stanchev, P.;Buck, B.;Szalai, J. P.;Parker, J.;Szekely, C.;Bronskill, M. J.",1997,Dec,,0,
3387,Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia,"The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2-weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.",amyloid;cysteine ethyl ester tc 99m;Pittsburgh compound B;aged;amnesia;article;basal ganglion;brain blood flow;brain cortex;case report;cognition;disease severity;drug uptake;frontal lobe;gait disorder;human;hypertension;intellectual impairment;laboratory test;lacunar stroke;male;memory disorder;multiinfarct dementia;neurologic examination;nuclear magnetic resonance imaging;positron emission tomography;right hemisphere;single photon emission computed tomography;subcortical ischemic vascular dementia;susceptibility weighted imaging;urge incontinence;vascular amyloidosis;very elderly;white matter,"Kida, H.;Satoh, M.;Ii, Y.;Fukuyama, H.;Maeda, M.;Tomimoto, H.",2017,,10.1111/psyg.12187,0,3388
3388,Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia,"The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.",,"Kida, H.;Satoh, M.;Ii, Y.;Fukuyama, H.;Maeda, M.;Tomimoto, H.",2016,Jan 18,10.1111/psyg.12187,0,
3389,Magnetic resonance imaging of the ageing brain,"Many changes occur in the brain with normal ageing. These have been extensively investigated by autopsy studies and more recently with high resolution MRI. Dementia is a major public health problem worldwide which affects the elderly population. Magnetic resonance imaging (MRI) is the imaging test of choice to identify underlying treatable causes of dementia, including normal pressure hydrocephalus, subdural haematoma and intracranial tumour. It is important to understand the normal changes which occur with ageing and these should not be interpreted as pathological lesions on MRI. Though there is considerable overlap between findings of normal and abnormal ageing brain, with a good clinical background, it is possible, in many cases, to suggest the diagnosis of Alzheimer's disease, multi-infarct dementia and various other pathological processes.",,"Khujneri, R.;De Sousa, J. A.",1997,1997,,0,
3390,Magnetic resonance spectroscopy and analysis of MECP2 in Rett syndrome,"We studied the in vivo cerebral metabolites and documented the presence of MECP2 gene mutations in six Chinese females with Rett syndrome. Magnetic resonance spectroscopy spectra from the frontal lobe (gray and white matter) and deep gray nuclei (basal ganglia and thalamus) of either side were obtained. N-acetylaspartate/total creatine, choline/total creatine, and N-acetylaspartate/choline ratios were analyzed and compared with six healthy age-matched female control subjects. MECP2 gene mutation was identified in four patients; one patient had polymorphism and one patient did not have gene mutation. N-acetylaspartate/total creatine of the frontal lobe of all patients (mean: 2.63, S.D. = 0.33) was decreased compared with age-matched control subjects (mean: 3.15, S.D. = 0.27), and the difference was statistically significant (P = 0.017) with a mean difference of 0.52 (95% CI = 0.68-0.36). The difference in all other metabolite ratios in the frontal lobe and deep gray nuclei were not statistically significant compared with age-matched control subjects. Mild frontal lobe and anterior temporal lobe atrophy was present in three patients. Proton-magnetic resonance spectroscopy is a sensitive method capable of detecting the biochemical changes in Rett syndrome and is able to detect changes before conventional magnetic resonance imaging. Our preliminary results suggest that reduction in N-acetylaspartate/total creatine ratio may not be related to the MECP2 mutation. Copyright © 2002 Elsevier Science Inc.",,"Khong, P. L.;Lam, C. W.;Ooi, C. G. C.;Ko, C. H.;Wong, V. C. N.",2002,2002,,0,
3391,"Early diagnosis of Alzheimer's disease based on partial least squares, principal component analysis and support vector machine using segmented MRI images","Computer aided diagnosis (CAD) systems using functional and structural imaging techniques enable physicians to detect early stages of the Alzheimer[U+05F3]s disease (AD). For this purpose, magnetic resonance imaging (MRI) have been proved to be very useful in the assessment of pathological tissues in AD. This paper presents a new CAD system that allows the early AD diagnosis using tissue-segmented brain images. The proposed methodology aims to discriminate between AD, mild cognitive impairment (MCI) and elderly normal control (NC) subjects and is based on several multivariate approaches, such as partial least squares (PLS) and principal component analysis (PCA). In this study, 188 AD patients, 401 MCI patients and 229 control subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were studied. Automated brain tissue segmentation was performed for each image obtaining gray matter (GM) and white matter (WM) tissue distributions. The validity of the analyzed methods was tested on the ADNI database by implementing support vector machine classifiers with linear or radial basis function (RBF) kernels to distinguish between normal subjects and AD patients. The performance of our methodology is validated using k-fold cross technique where the system based on PLS feature extraction and linear SVM classifier outperformed the PCA method. In addition, PLS feature extraction is found to be more effective for extracting discriminative information from the data. In this regard, the developed latter CAD system yielded maximum sensitivity, specificity and accuracy values of 85.11%, 91.27% and 88.49%, respectively.",,"Khedher, L.;Ramírez, J.;Górriz, J. M.;Brahim, A.;Segovia, F.",2015,2015,,0,
3392,Automatic classification of segmented MRI data combining Independent Component Analysis and Support Vector Machines,"This paper proposes a novel method for automatic classification of magnetic resonance images (MRI) based on independent component analysis (ICA). Our methodology consists of three processing steps. First, all the MRI scans are normalized and segmented into gray matter, white matter and cerebrospinal fluid. Then, ICA is applied to the preprocessed images for extracting relevant features which will be used as inputs to a support vector machine (SVM) classifier in order to reduce the feature space dimensionality. The system discriminates between Alzheimer's disease (AD) patients, mild cognitive impairment (MCI), and normal control (NC) subjects. All MRI data used in this work were obtained from the Alzheimers Disease Neuroimaging Initiative (ADNI). The experimental results showed that our methodology can successfully discriminate AD and MCI patients from NC subjects.",,"Khedher, L.;Ramirez, J.;Gorriz, J. M.;Brahim, A.",2014,,,0,
3393,Chronic kidney disease is associated with white matter hyperintensity volume: the Northern Manhattan Study (NOMAS),"BACKGROUND AND PURPOSE: White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. METHODS: The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race-ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. RESULTS: Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (beta 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (beta 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (beta 1.479; 95% CI, 1.067 to 2.050). CONCLUSIONS: The association between moderate-severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy.","Aged;Brain/metabolism/*pathology;Cerebrovascular Circulation;Chronic Disease;Endothelium, Vascular/pathology/*physiology;Female;Glomerular Filtration Rate;Humans;Kidney/pathology;Kidney Diseases/*pathology/*therapy;Magnetic Resonance Imaging/methods;Male;Middle Aged;New York;Renal Insufficiency/metabolism;Risk Factors","Khatri, M.;Wright, C. B.;Nickolas, T. L.;Yoshita, M.;Paik, M. C.;Kranwinkel, G.;Sacco, R. L.;DeCarli, C.",2007,Dec,10.1161/strokeaha.107.493593,0,
3394,Recent advances in neuroimaging biomarkers in geriatric psychiatry,"Neuroimaging, both structural and functional, serve as useful adjuncts to clinical assessment, and can provide objective, reliable means of assessing disease presence and process in the aging population. In the following review we briefly explain current imaging methodologies. Then, we analyze recent developments in developing neuroimaging biomarkers for two highly prevalent disorders in the elderly population- Alzheimer's disease (AD) and late-life depression (LLD). In AD, efforts are focused on early diagnosis through in vivo visualization of disease pathophysiology. In LLD, recent imaging evidence supports the role of white matter ischemic changes in the pathogenesis of depression in the elderly, the ""vascular hypothesis."" Finally, we discuss potential roles for neuroimaging biomarkers in geriatric psychiatry in the future.",Age of Onset;Aged;Alzheimer Disease/ diagnosis;Biomarkers/analysis;Depressive Disorder/ diagnosis;Geriatric Psychiatry/ methods;Humans;Neuroimaging/ methods,"Khandai, A. C.;Aizenstein, H. J.",2013,Jun,10.1007/s11920-013-0360-9,0,
3395,A biophysical model of shape changes due to atrophy in the brain with Alzheimer's disease,"This paper proposes a model of brain deformation triggered by atrophy in Alzheimer's Disease (AD). We introduce a macroscopic biophysical model assuming that the density of the brain remains constant, hence its volume shrinks when neurons die in AD. The deformation in the brain parenchyma minimizes the elastic strain energy with the prescribed local volume loss. The cerebrospinal fluid (CSF) is modelled differently to allow for fluid readjustments occuring at a much faster time-scale. PDEs describing the model is discretized in staggered grid and solved using Finite Difference Method. We illustrate the power of the model by showing different deformation patterns obtained for the same global atrophy but prescribed in gray matter (GM) or white matter (WM) on a generic atlas MRI, and with a realistic AD simulation on a subject MRI. This well-grounded forward model opens a way to study different hypotheses about the distribution of brain atrophy, and to study its impact on the observed changes in MR images.","Algorithms;Alzheimer Disease/ pathology;Atrophy/pathology;Brain/ pathology;Computer Simulation;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Models, Anatomic;Models, Neurological;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Khanal, B.;Lorenzi, M.;Ayache, N.;Pennec, X.",2014,,,0,
3396,Remote ischemic postconditioning: harnessing endogenous protection in a murine model of vascular cognitive impairment,"We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Abeta), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Abeta, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional therapy for aged individuals with VCI. The mechanisms by which RIPostC improves CBF and attenuates tissue damage need to be investigated in the future.","Amyloid beta-Peptides/metabolism;Animals;Brain Ischemia/complications/psychology/ therapy;Carotid Stenosis/complications/psychology/ therapy;Cell Death;Cerebral Cortex/ blood supply/metabolism/pathology;Dementia, Vascular/etiology/ therapy;Disease Models, Animal;Encephalitis/metabolism;Ischemic Postconditioning;Male;Mice;Mice, Inbred C57BL;Myelin Sheath/pathology;Recognition (Psychology)/physiology;White Matter/pathology","Khan, M. B.;Hoda, M. N.;Vaibhav, K.;Giri, S.;Wang, P.;Waller, J. L.;Ergul, A.;Dhandapani, K. M.;Fagan, S. C.;Hess, D. C.",2015,Feb,10.1007/s12975-014-0374-6,0,
3397,Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model,"Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of the cases of dementia. The purpose of this study was to determine the effect of chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months) outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS + sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO). CBF, cognitive impairment, and functional outcomes were performed up for 6 months after BCAS surgery. The expression of CD31, alpha-SMA, and myelin basic protein (MBP) was assessed by immunohistochemistry (IHC). Additional set of mice were randomized to sham, BCAS, and BCAS+C-RIC. The cerebrovascular angioarchitecture was studied with micro-CT. RIC therapy for either 1 or 4 months significantly improved CBF, new collateral formation, functional and cognitive outcomes, and prevented white matter damage. There was no difference between C-RIC for 1 or 4 months; IHC studies at 6 months showed an increase in brain CD31 and alpha-SMA expression indicating increased angiogenesis and MBP indicating preservation of white matter in animals receiving RIC. One month of daily RIC is as effective as 4 months of daily RIC in improving CBF, angiogenesis, and long-term functional outcomes (6 months) in a VCID model. This suggests that 1 month of RIC is sufficient to reduce cognitive impairment and induce beneficial cerebrovascular remodeling.","Angiogenesis, collateral remodeling, white matter degeneration;Cerebral blood flow (CBF);Chronic remote ischemic conditioning (C-RIC);Vascular contributions to cognitive impairment and dementia (VCID)","Khan, M. B.;Hafez, S.;Hoda, M. N.;Baban, B.;Wagner, J.;Awad, M. E.;Sangabathula, H.;Haigh, S.;Elsalanty, M.;Waller, J. L.;Hess, D. C.",2018,Feb,,0,
3398,Cholinergic neuronal deficits in CADASIL,"BACKGROUND AND PURPOSE: Previous evidence from MRI and acetylcholinesterase histochemistry suggests cholinergic fibers are affected in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: As a measure of cholinergic function, we assessed choline acetyltransferase (ChAT) activities in the frontal and temporal neocortices and the immunocytochemical distribution of ChAT and p75 neurotrophin receptor (P75(NTR)) by in vitro imaging in the nucleus basalis of Meynert of CADASIL subjects. RESULTS: ChAT activities were significantly reduced by 60% to 70% in frontal and temporal cortices of CADASIL cases, as were ChAT and P75(NTR) immunoreactivities in the nucleus basalis. CONCLUSIONS: Our findings suggest cholinergic neuronal impairment in CADASIL and implicate cholinomimetic therapy for subcortical vascular dementias.","Aged;Aged, 80 and over;Basal Nucleus of Meynert/ metabolism/pathology;CADASIL/ metabolism/pathology;Cerebral Arteries/metabolism/pathology;Choline O-Acetyltransferase/ metabolism;Cholinergic Fibers/ metabolism/pathology;Down-Regulation/physiology;Female;Frontal Lobe/ metabolism/pathology;Humans;Immunohistochemistry;Male;Middle Aged;Neural Pathways/ metabolism/pathology;Receptor, Nerve Growth Factor/metabolism;Temporal Lobe/ metabolism/pathology","Keverne, J. S.;Low, W. C.;Ziabreva, I.;Court, J. A.;Oakley, A. E.;Kalaria, R. N.",2007,Jan,10.1161/01.str.0000251787.90695.05,0,
3399,MRI findings in patients on placebo in phase 3 clinical trials of mild-moderate Alzheimer's disease,"Objective: to assess brain MRI findings using systematic, standardized methods in 990 placebo patients observed over 18 months in 2 phase 3 placebo-controlled clinical trials of bapineuzumab iV in mild to moderate Alzheimer's Disease (AD). Background: amyloid-related imaging abnormalities (aria) are a relatively new MRI finding and consist of ARIA-E (with effusion or edema) and ARIA-H (with hemosiderin deposition, both small and large). There are differences in training, experience, use of central readers and the population being assessed that may explain the variability in MRI observations to date. Methods: Baseline MRI exclusion criteria were > 1 hemosiderin deposit (HD), hemorrhage, >1 lacunar infarct, large infarct, space occupying lesions, contusion, encephalomalacia, aneurisms, vascular malformation or subdural hematoma. Subjects were scanned approximately every 3 months for 18 months. A retrospective analysis of all MRI scans obtained in placebo patients in an APOE*E4 non carrier study (542 patients) and an APOE*E4 carrier study (448 patients) was performed after each subject had completed trial participation. Five pairs of trained neuroradiologists, blinded to treatment assignment and clinical information, reviewed and quantified the extent and location of pathological findings on baseline and follow up MRI scans using standardized methods and scoring systems for aria-e, aria-h (HD<10 mm, >10mm) and age-related white matter disease (ARWMC). Parenchymal hemorrhage, and other findings such as subdural hematoma, stroke and space occupying lesion were also recorded. A neuroradiologist pair individually reviewed each patient's series of MRI scans using a sequential, locked process. Differences in the final results were adjudicated by reader pair consensus and the consensus results were analyzed. Results: the incidence proportion of treatment-emergent (te) aria-e was higher in APOE*E4 carriers (5, 1.1%) than in non-carriers (3, 0.6%), but did not vary substantially with the number of e4 alleles present. The radiologic severity score was low (<5/180) in all cases and the mean duration was 136 days in 1 APOE*E4 carriers and 110 days inAPOE*E4 non carriers. The baseline prevalence of HD<10 mm was 17% in both APOE*E4 carriers and APOE*E4 non carriers. The incidence proportion of te aria-h (small HD <10 mm) was higher in APOE*E4 carriers (21% with 1 APOE*E4 allele and 34% with 2 APOE*E4 alleles) than APOE*E4 non-carriers (17%). The incidence proportion of large HD (>10 mm) was also higher in APOE*E4 carriers (1.8% with 1 APOE*E4 allele and 5.4% with 2 APOE*E4 alleles) than in APOE*E4 non carriers (1.3%). The vast majority of subjects did not develop HD > 10 mm. ARWMC was present at baseline in 68% of APOE*E4 carriers and 70% of APOE*E4 non carriers; 8% of APOE*E4 carriers and 10% of APOE*E4 non carriers had a score >7/30 equivalent to involvement of approximately 25% of white matter. The mean ARWMC scores did not increase over 18 months. The incidence proportion of other findings in APOE*E4 carriers was 0.2% for parenchymal hemorrhages, 2.0% for all infarcts and 1.1% for subdural hematomas and in APOE*E4 non carriers was 0% for parenchymal hemorrhages, 3.8% for all infarcts and 1.3% for subdural hematomas. Conclusions: AD patients who have not been treated with monoclonal antibodies also develop spontaneous aria-e. Despite the exclusion of >1 MH at screening, approximately 1/3APOE*E4 carriers and 1/5APOE*E4 non-carriers developed incident HD<10 mm during the study. APOE *E4 carriers developed incident aria-e and aria-h more frequently than: APOE *E4 non carriers but not ARWMC. This study highlights that MRI findings may have an impact on inclusion and exclusion criteria of future trials and it may be important to exclude patients with dementia of mixed etiologies with high ARWMC scores.",human;clinical trial (topic);Alzheimer disease;patient;phase 3 clinical trial;nuclear magnetic resonance imaging;allele;subdural hematoma;infarction;bleeding;reading;white matter;consensus;encephalomalacia;contusion;imaging;controlled clinical trial (topic);prevalence;population;cerebrovascular accident;brain;scoring system;follow up;screening;dementia;etiology;congenital blood vessel malformation;edema;aneurysm;effusion;placebo;hemosiderin;monoclonal antibody;amyloid;bapineuzumab,"Ketter, N.;Brashear, H. R.;Miaux, Y.;Purcell, D. D.;Barkhof, F.;Gass, A.;Collins, P.;Miloslavsky, M.;McGovern, M.;Morris, K.;Guenzler, V.;Arrighi, H. M.",2013,,,0,
3400,Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients,"BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE varepsilon4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE varepsilon4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described. RESULTS: In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE varepsilon4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10 mm (cerebral microhemorrhages) was higher in active groups versus placebo. CONCLUSION: ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study.",Alzheimer's disease;NCT00575055 (Bapineuzumab-302);bapineuzumab;brain amyloid-related imaging abnormality;magnetic resonance imaging Registration: NCT00574132 (Bapineuzumab-301),"Ketter, N.;Brashear, H. R.;Bogert, J.;Di, J.;Miaux, Y.;Gass, A.;Purcell, D. D.;Barkhof, F.;Arrighi, H. M.",2017,,,0,
3401,"Lymphomatosis cerebri presenting with orthostatic hypotension, anorexia, and paraparesis","To increase awareness about lymphomatosis cerebri by describing a patient with a unique presentation Case report a 58 year old woman presented with progressive lower extremity weakness, postural hypotension, and 90 pound weight loss over 3 months a brain magnetic resonance image revealed multiple non-enhancing foci of T2 hyperintensity in the periventricular white matter despite treatment with corticosteroids, she expired autopsy demonstrated normal gross appearance of the brain and spinal cord microscopic inspection revealed diffuse infiltration of the central nervous system (CNS) parenchyma and white matter by large atypical B cells, consistent with a diagnosis of lymphomatosis cerebri lymphomatosis cerebri is a primary CNS lymphoma variant that is poorly recognized and often misdiagnosed it commonly presents as a rapidly progressive dementia, although patients may present with neurologic dysfunction without dementia diagnosis requires a pathological examination treatment with intravenous high-dose methotrexate based chemotherapy should be considered in appropriate patients. © Springer Science+Business Media, LLC. 2012.",,"Keswani, A.;Bigio, E.;Grimm, S.",2012,September,,0,
3402,Associations between cerebral small-vessel disease and Alzheimer disease pathology as measured by cerebrospinal fluid biomarkers,"IMPORTANCE: It remains unclear if and how associations between cerebral small-vessel disease and Alzheimer disease (AD) pathology lead to cognitive decline and dementia. OBJECTIVE: To determine associations between small-vessel disease and AD pathology. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study from January 2002 to December 2012 using the memory clinic-based Amsterdam Dementia Cohort. The study included 914 consecutive patients with available cerebrospinal fluid (CSF) and magnetic resonance imaging; 547 were patients diagnosed as having AD (54% female, mean [SD], 67 [8]; Mini-Mental State Examination score, mean [SD], 21 [5]), 30 were patients diagnosed as having vascular dementia (37% female, mean [SD], 76 [9]; Mini-Mental State Examination score, mean [SD], 24 [4]), and 337 were control participants with subjective memory complaints (42% female, mean [SD], 59 [59]; Mini-Mental State Examination score, mean [SD], 28 [2]). Linear regressions were performed with CSF biomarkers (log transformed) as dependent variables and magnetic resonance imaging measures (dichotomized) as independent, adjusted for sex, age, mediotemporal lobe atrophy, and diagnosis. An interaction term for diagnosis by magnetic resonance imaging measures was used for estimates per diagnostic group. MAIN OUTCOMES AND MEASURES: We examined the associations of magnetic resonance imaging white matter hyperintensities (WMH), lacunes, microbleeds with CSF beta-amyloid 42 (Abeta42), total tau, and tau phosphorylated at threonine 181 (P-tau181) as well as for a subset of apolipoprotein E (APOE) epsilon4 carriers and noncarriers. RESULTS: Microbleed presence was associated with lower CSF Abeta42 in AD and vascular dementia (standardized beta = -0.09, P = .003; standardized beta = -0.30, P = .01), and higher CSF tau in controls (standardized beta = 0.10, P = .03). There were no effects for P-tau181. The presence of WMH was associated with lower Abeta42 in control participants and patients with vascular dementia (standardized beta = -0.18, P = .002; standardized beta = -0.32, P = .02) but not in patients with AD. There were no effects for tau or P-tau181. The presence of lacunes was associated with higher Abeta42 in vascular dementia (standardized beta = 0.17, P = .07) and lower tau in AD (standardized beta = -0.07, P = .05) but there were no effects for Abeta42 or P-tau181. Stratification for apolipoprotein E genotype revealed that these effects were mostly attributable to epsilon4 carriers. CONCLUSIONS AND RELEVANCE: Deposition of amyloid appears aggravated in patients with cerebral small-vessel disease, especially in apolipoprotein E epsilon4 carriers, providing evidence for pathophysiological synergy between these 3 biological factors.","Aged;Alzheimer Disease/ cerebrospinal fluid/metabolism/ pathology;Amyloid beta-Peptides/cerebrospinal fluid/metabolism;Apolipoprotein E4/cerebrospinal fluid/metabolism;Biomarkers/cerebrospinal fluid/metabolism;Cerebral Small Vessel Diseases/ cerebrospinal fluid/metabolism/ pathology;Cross-Sectional Studies;Female;Hemorrhage/blood/cerebrospinal fluid/pathology;Heterozygote Detection;Humans;Male;Middle Aged;Peptide Fragments/cerebrospinal fluid/metabolism;Phosphorylation;Stroke, Lacunar/blood/cerebrospinal fluid/pathology;tau Proteins/cerebrospinal fluid/metabolism","Kester, M. I.;Goos, J. D.;Teunissen, C. E.;Benedictus, M. R.;Bouwman, F. H.;Wattjes, M. P.;Barkhof, F.;Scheltens, P.;van der Flier, W. M.",2014,Jul 1,10.1001/jamaneurol.2014.754,0,
3403,Cognition and white matter changes on magnetic resonance imaging in dementia,"In a prospective magnetic resonance imaging and cognitive study of 38 demented patients and 15 control subjects, 11 of 27 patients with Alzheimer's disease and 8 of 11 patients with vascular dementia had significant periventricular hyperintensities. Memory and language testing in the early investigation of dementia is useful to distinguish patients with or without periventricular hyperintensities on magnetic resonance imaging. Patients without periventricular hyperintensities are worse on memory and conceptualization tests than patients with periventricular hyperintensities, who tend to be worse on comprehension and attention tests. These differences in cognitive pattern are present between patients with different pathogenesis who are otherwise matched for dementia severity. Language and some nonverbal cognitive deficits correlate with the extent of cortical and ventricular atrophy in Alzheimer's disease.","Aged;Alzheimer Disease/diagnosis;Brain/ pathology;Cognition;Dementia/diagnosis/pathology/ physiopathology;Dementia, Multi-Infarct/diagnosis;Discriminant Analysis;Humans;Language Tests;Magnetic Resonance Imaging;Male;Memory;Neuropsychological Tests;Psychiatric Status Rating Scales","Kertesz, A.;Polk, M.;Carr, T.",1990,Apr,,0,
3404,Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions,"Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.",aging;brain atrophy;cerebrovascular disease;cognition;hypertension;scaled subprofile model;voxel-based morphometry;white matter hyperintensities,"Kern, K. C.;Wright, C. B.;Bergfield, K. L.;Fitzhugh, M. C.;Chen, K.;Moeller, J. R.;Nabizadeh, N.;Elkind, M. S. V.;Sacco, R. L.;Stern, Y.;DeCarli, C. S.;Alexander, G. E.",2017,,,0,
3405,Calcium supplementation and risk of dementia in women with cerebrovascular disease,"OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.","0 (Apolipoprotein E4);0 (Calcium, Dietary);0 (Estrogens);1406-16-2 (Vitamin D);V27W9254FZ (Cortisone);Aged;Apolipoprotein E4/genetics;Brain/diagnostic imaging;Calcium, Dietary/ administration & dosage;Cortisone/administration & dosage;Dementia/complications/ diet therapy/epidemiology/genetics;Dietary Supplements;Estrogens/administration & dosage;Female;Follow-Up Studies;Hormone Replacement Therapy;Humans;Longitudinal Studies;Osteoporotic Fractures/complications/diet therapy/epidemiology/genetics;Prospective Studies;Risk;Stroke/complications/diet therapy/epidemiology/genetics;Sweden;Treatment Failure;Vitamin D/administration & dosage","Kern, J.;Kern, S.;Blennow, K.;Zetterberg, H.;Waern, M.;Guo, X.;Borjesson-Hanson, A.;Skoog, I.;Ostling, S.",2016,Oct 18,,0,3406
3406,Calcium supplementation and risk of dementia in women with cerebrovascular disease,"OBJECTIVE: To determine whether calcium supplementation is associated with the development of dementia in women after a 5-year follow-up. METHODS: This was a longitudinal population-based study. The sample was derived from the Prospective Population Study of Women and H70 Birth Cohort Study in Gothenburg, Sweden, and included 700 dementia-free women aged 70-92 years. At baseline in 2000-2001, and at follow-up in 2005-2006, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: Women treated with calcium supplements (n = 98) were at a higher risk of developing dementia (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.01-4.37, p = 0.046) and the subtype stroke-related dementia (vascular dementia and mixed dementia) (OR 4.40, 95% CI 1.54-12.61, p = 0.006) than women not given supplementation (n = 602). In stratified analyses, calcium supplementation was associated with the development of dementia in groups with a history of stroke (OR 6.77, 95% CI 1.36-33.75, p = 0.020) or presence of white matter lesions (OR 2.99, 95% CI 1.28-6.96, p = 0.011), but not in groups without these conditions. CONCLUSIONS: Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease. Because our sample was relatively small and the study was observational, these findings need to be confirmed.",,"Kern, J.;Kern, S.;Blennow, K.;Zetterberg, H.;Waern, M.;Guo, X.;Borjesson-Hanson, A.;Skoog, I.;Ostling, S.",2016,Aug 17,10.1212/wnl.0000000000003111,0,
3407,Basal forebrain atrophy correlates with amyloid beta burden in Alzheimer's disease,"The brains of patients suffering from Alzheimer's disease (AD) have three classical pathological hallmarks: amyloid-beta (Abeta) plaques, tau tangles, and neurodegeneration, including that of cholinergic neurons of the basal forebrain. However the relationship between Abeta burden and basal forebrain degeneration has not been extensively studied. To investigate this association, basal forebrain volumes were determined from magnetic resonance images of controls, subjects with amnestic mild cognitive impairment (aMCI) and AD patients enrolled in the longitudinal Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL) studies. In the AIBL cohort, these volumes were correlated within groups to neocortical gray matter retention of Pittsburgh compound B (PiB) from positron emission tomography images as a measure of Abeta load. The basal forebrain volumes of AD and aMCI subjects were significantly reduced compared to those of control subjects. Anterior basal forebrain volume was significantly correlated to neocortical PiB retention in AD subjects and aMCI subjects with high Abeta burden, whereas posterior basal forebrain volume was significantly correlated to neocortical PiB retention in control subjects with high Abeta burden. Therefore this study provides new evidence for a correlation between neocortical Abeta accumulation and basal forebrain degeneration. In addition, cluster analysis showed that subjects with a whole basal forebrain volume below a determined cut-off value had a 7 times higher risk of having a worse diagnosis within ~18 months.","Aged;Alzheimer Disease/ pathology/radionuclide imaging;Amyloid beta-Peptides/ analysis;Atrophy/pathology;Basal Forebrain/ pathology/radionuclide imaging;Disease Progression;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ pathology/radionuclide imaging;Positron-Emission Tomography","Kerbler, G. M.;Fripp, J.;Rowe, C. C.;Villemagne, V. L.;Salvado, O.;Rose, S.;Coulson, E. J.",2015,,10.1016/j.nicl.2014.11.015,0,
3408,PET imaging of neuropathology in tauopathies: Progressive supranuclear palsy,"Objective: Currently [(18)F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [(18)F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-β deposits. Methods: Fifteen patients with PSP received [(18)F]FDDNP PET scanning. [(18)F]FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders. Results: [(18)F]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [(18)F]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [(18)F]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease. Conclusions: These results provide evidence that [(18)F]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [(18)F]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [(18)F]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult. © 2013 - IOS Press and the authors. All rights reserved.",,"Kepe, V.;Bordelon, Y.;Boxer, A.;Huang, S. C.;Liu, J.;Thiede, F. C.;Mazziotta, J. C.;Mendez, M. F.;Donoghue, N.;Small, G. W.;Barrio, J. R.",2013,2013,,0,
3409,Carotid sinus syndrome is common in dementia with Lewy bodies and correlates with deep white matter lesions,"BACKGROUND: Carotid sinus syndrome (CSS) is a common cause of syncope in older persons. There appears to be a high prevalence of carotid sinus hypersensitivity (CSH) in patients with dementia with Lewy bodies (DLB) but not in Alzheimer's disease. OBJECTIVE: To compare the prevalence of CSH in DLB and Alzheimer's disease, and to determine whether there is an association between CSH induced hypotension and brain white matter hyperintensities on magnetic resonance imaging (MRI). METHODS: Prevalence of CSH was compared in 38 patients with DLB (mean (SD) age, 76 (7) years), 52 with Alzheimer's disease (80 (6) years), and 31 case controls (73 (5) years) during right sided supine carotid sinus massage (CSM). CSH was defined as cardioinhibitory (CICSH; >3 s asystole) or vasodepressor (VDCSH; >30 mm Hg fall in systolic blood pressure (SBP)). T2 weighted brain MRI was done in 45 patients (23 DLB, 22 Alzheimer). Hyperintensities were rated by the Scheltens scale. RESULTS: Overall heart rate response to CSM was slower (RR interval = 3370 ms (640 to 9400)) and the proportion of patients with CICSH greater (32%) in DLB than in Alzheimer's disease (1570 (720 to 7800); 11.1%) or controls (1600 (720 to 3300); 3.2%) (p<0.01)). The strongest predictor of heart rate slowing and CSH was a diagnosis of DLB (Wald 8.0, p<0.005). The fall in SBP during carotid sinus massage was greater with DLB (40 (22) mm Hg) than with Alzheimer's disease (30 (19) mm Hg) or controls (24 (19) mm Hg) (both p<0.02). Deep white matter hyperintensities were present in 29 patients (64%). In DLB, there was a correlation between magnitude of fall in SBP during CSM and severity of deep white matter changes (R = 0.58, p = 0.005). CONCLUSIONS: Heart rate responses to CSM are prolonged in patients with DLB, causing hypotension. Deep white matter changes from microvascular disease correlated with the fall in SBP. Microvascular pathology is a key substrate of cognitive impairment and could be reversible in DLB where there are exaggerated heart rate responses to carotid sinus stimulation.",Aged;Alzheimer Disease/ epidemiology/ pathology;Brain/ pathology;Comorbidity;Electrocardiography;Female;Heart Rate/physiology;Humans;Lewy Body Disease/ epidemiology/ pathology;Logistic Models;Magnetic Resonance Imaging;Male;Prevalence;Syncope/ epidemiology/physiopathology,"Kenny, R. A.;Shaw, F. E.;O'Brien, J. T.;Scheltens, P. H.;Kalaria, R.;Ballard, C.",2004,Jul,,0,
3410,Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies,"We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.",tau protein;adult;aged;amyloid plaque;brain;case report;complication;dementia;diagnostic imaging;female;human;male;metabolism;middle aged;neurofibrillary tangle;neuroimaging;nuclear magnetic resonance imaging;pathology;traumatic brain injury,"Kenney, K.;Iacono, D.;Edlow, B. L.;Katz, D. I.;Diaz-Arrastia, R.;Dams-O'Connor, K.;Daneshvar, D. H.;Stevens, A.;Moreau, A. L.;Tirrell, L. S.;Varjabedian, A.;Yendiki, A.;van der Kouwe, A.;Mareyam, A.;McNab, J. A.;Gordon, W. A.;Fischl, B.;McKee, A. C.;Perl, D. P.",2018,,10.1093/jnen/nlx101,0,
3411,Chromosome 14 linked familial Alzheimer's disease: A clinico-pathological study of a single pedigree,"The clinical features of three affected members of a British pedigree with familial Alzheimer's disease are presented. This pedigree is one of six included in an earlier study which demonstrated linkage to chromosome 14. The individuals were investigated clinically and neuropsychologically: using both PET and MRI over a 4-year period. Further information from three deceased individuals was obtained including histopathological confirmation of Alzheimer's disease in one case which came to autopsy. The mean age at onset for this family was 43 years. Neurological examination revealed myoclonic jerks in all cases, and one patient was documented to have seizures. Strikingly similar neuropsychological profiles were observed, characterized by an initial memory deficit with early dyscalculia and an impairment in speech production with relative absence of anemia. All individuals showed mild degrees of cerebral atrophy and two individuals had periventricular white matter lesions. PET scanning using [18F]fluorodeoxyglucose showed parieto-temporal hypometabolism in all cases and the two severely affected patients with speech production changes had additional left-sided frontal hypometabolism involving Broca's urea. The least affected case initially had a more asymmetrical reduction in metabolism in the left inferior temporal and supramarginal gyri; a follow-up scan showed that this deficit had become bilateral and more severe. These clinical and neuroimaging features have not been previously reported in chromosome 14 linked pedigrees; the phenotypic variability between families suggests allelic heterogeneity at the chromosome 14 locus.",fluorodeoxyglucose f 18;glucose;adult;Alzheimer disease;article;brain atrophy;brain metabolism;case report;chromosome 14;clinical feature;familial disease;genetic linkage;glucose metabolism;histopathology;human;human tissue;neurologic examination;neuropathology;neuropsychology;nuclear magnetic resonance imaging;onset age;pedigree analysis;positron emission tomography;priority journal;seizure;speech disorder;white matter,"Kennedy, A. M.;Newman, S. K.;Frackowiak, R. S. J.;Cunningham, V. J.;Roques, P.;Stevens, J.;Neary, D.;Bruton, C. J.;Warrington, E. K.;Rossor, M. N.",1995,,,0,
3412,Triphasic EEG pattern in bilateral paramedian thalamic infarction,"Two cases of bilateral paramedian thalamic infarction (BPTI) showing triphasic waves (TWs) on the electroencephalogram (EEG) at acute stage are presented in this study. BPTI is a rare syndrome with decreased level of consciousness, gaze abnormalities and cognitive deterioration. TWs are nonspecific EEG findings occurring in both metabolic and nonmetabolic conditions. The TWs in BPTI might be related to level of consciousness and does not always predict a poor prognosis in BPTI.",electrolyte;liver enzyme;troponin;aged;arterial gas;article;bilateral paramedian thalamic infarction;blood cell count;blood clotting test;brain infarction;case report;computer assisted tomography;consciousness level;Doppler echography;electroencephalogram;eye movement disorder;female;gaze paralysis;Glasgow coma scale;human;laboratory test;mental deterioration;neurologic examination;nuclear magnetic resonance imaging;priority journal;stupor;theta rhythm;wakefulness,"Kenangil, G.;Orken, D. N.;Yalcin, D.;Gündogdu, L.;Forta, H.",2008,,,0,
3413,Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study,"OBJECTIVE: To investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors. METHODS: A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain (11)C-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment. White matter lesions were visually rated from MRIs by a semiquantitative Fazekas score. RESULTS: Twenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with APOE epsilon4 allele (50%), and showed slightly better glucose homeostasis compared to PiB-negative participants. PiB-positive and -negative participants did not differ significantly in other cognitive domain scores or other vascular risk factors. There was no significant difference in Fazekas score between the PiB groups. CONCLUSIONS: The high percentage of PiB-positive participants provides evidence of a successful recruitment process of the at-risk population in the main FINGER intervention trial. The results suggest a possible association between early brain amyloid accumulation and decline in executive functions. APOE epsilon4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.",,"Kemppainen, N.;Johansson, J.;Teuho, J.;Parkkola, R.;Joutsa, J.;Ngandu, T.;Solomon, A.;Stephen, R.;Liu, Y.;Hanninen, T.;Paajanen, T.;Laatikainen, T.;Soininen, H.;Jula, A.;Rokka, J.;Rissanen, E.;Vahlberg, T.;Peltoniemi, J.;Kivipelto, M.;Rinne, J. O.",2018,Jan 16,,0,
3414,"Unexplained high fever in an elderly patient treated with clonidine, duloxetine, and atorvastatin","Background: Drug-induced fever is a clinical diagnosis and should always be considered when the fever is constant and high without a clear source of infection. Although drug-induced fever has been reported with other centrally acting antihypertensive drugs such as methyldopa, published reports of this adverse effect with clonidine in humans were not identified in a search of the literature. Case summary: A 66-year-old institutionalized white female with a history of morbid obesity (body mass index, 40 kg/m2), Alzheimer's dementia, hypertension, and depression presented to a hospital in Boston, Massachusetts (Caritas Saint Elizabeth's Medical Center) with generalized weakness and shortness of breath and was found to have a non-ST segment elevation myocardial infarction. Before hospitalization, the patient was taking memantine 10 mg PO BID, donepezil 10 mg PO once daily, duloxetine 60 mg PO once daily, clonidine 0.1 mg PO TID, metoprolol 50 mg PO BID, and amlodipine 10 mg PO once daily. On admission, the patient was initiated on aspirin 325 mg, atorvastatin 80 mg, and clopidogrel 75 mg PO daily. Her dose of clonidine was increased to 0.2 mg PO TID to optimize blood pressure control, and metoprolol and amlodipine were continued at the same doses. The patient developed fever on the third day after the cardiac catheterization. The fever ranged from 99.0°F to 102.7°F. The physical examination, laboratory data analysis, multiple blood cultures, urinalysis, chest radiograph, and a computed tomography of the head, chest, abdomen, and pelvis did not reveal any source of infection. On the sixth day after admission, clonidine was reduced to the baseline dose of 0.1 mg PO TID and on the ninth day it was stopped. The patient was afebrile on the twelfth day and remained so for the duration of her hospitalization. Naranjo scores for her newly initiated concomitant medications were as follows: aspirin, 1; atorvastatin, 3; clonidine, 6; and clopidogrel, 1. The rating of 6 for clonidine suggests that it was probably associated with the fever in this patient. Conclusion: We describe a case of drug-induced fever probably associated with clonidine administration. The higher dose of clonidine alone or in interaction with duloxetine and atorvastatin may have contributed to the development of drug-induced fever. © 2009 Excerpta Medica Inc. All rights reserved.",acetylsalicylic acid;amlodipine;atorvastatin;clonidine;clopidogrel;donepezil;duloxetine;memantine;metoprolol;aged;Alzheimer disease;article;blood culture;blood pressure regulation;case report;computer assisted tomography;dementia;depression;drug dose increase;drug dose reduction;drug fever;drug megadose;drug withdrawal;female;heart catheterization;heart infarction;human;hypertension;laboratory test;morbid obesity;physical examination;thorax radiography;urinalysis,"Kelesidis, T.;Kelesidis, I.",2009,,,0,
3415,Collagenosis of the Deep Medullary Veins: An Underrecognized Pathologic Correlate of White Matter Hyperintensities and Periventricular Infarction?,"White matter hyperintensities (WMH) are prevalent. Although arteriolar disease has been implicated in their pathogenesis, venous pathology warrants consideration. We investigated relationships of WMH with histologic venous, arteriolar and white matter abnormalities and correlated findings with premortem neuroimaging. Three regions of periventricular white matter were sampled from archived autopsy brains of 24 pathologically confirmed Alzheimer disease (AD) and 18 age-matched nonAD patients. Using trichrome staining, venous collagenosis (VC) of periventricular veins (<150 microm in diameter) was scored for severity of wall thickening and occlusion; percent stenosis by collagenosis of large caliber (>200 microm) veins (laVS) was measured. Correlations were made between WMH in premortem neuroimaging and vascular and white matter pathology. We found greater VC (U(114) = 2092.5, p = 0.005 and U(114) = 2121.5, p = 0.002 for small and medium caliber veins, respectively) and greater laVS (t(110) = 3.46, p = 0.001) in patients with higher WMH scores; WMH scores correlated with VC (rs(114) = 0.27, p = 0.004) and laVS (rs(110) = 0.38, p < 0.001). By multiple linear regression analysis, the strongest predictor of WMH score was laVS (beta = 0.338, p < 0.0001). VC was frequent in patients with periventricular infarcts identified on imaging. We conclude that periventricular VC is associated with WMH in both AD and nonAD patients and the potential roles of VC in WMH pathogenesis merit further study.","Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/pathology;Autopsy;Cerebral Infarction/diagnostic imaging/ pathology;Cerebral Veins/diagnostic imaging/ pathology;Female;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Male;Medulla Oblongata/diagnostic imaging/ pathology;Middle Aged;Neuroimaging;White Matter/diagnostic imaging/ pathology;Alzheimer disease;Leukoaraiosis;Pathology;Veins;Venous collagenosis;White matter hyperintensities","Keith, J.;Gao, F. Q.;Noor, R.;Kiss, A.;Balasubramaniam, G.;Au, K.;Rogaeva, E.;Masellis, M.;Black, S. E.",2017,Apr 1,,0,
3416,An unbiased longitudinal analysis framework for tracking white matter changes using diffusion tensor imaging with application to Alzheimer's disease,"We introduce a novel image-processing framework for tracking longitudinal changes in white matter microstructure using diffusion tensor imaging (DTI). Charting the trajectory of such temporal changes offers new insight into disease progression but to do so accurately faces a number of challenges. Recent developments have highlighted the importance of processing each subject's data at multiple time points in an unbiased way. In this paper, we aim to highlight a different challenge critical to the processing of longitudinal DTI data, namely the approach to image alignment. Standard approaches in the literature align DTI data by registering the corresponding scalar-valued fractional anisotropy (FA) maps. We propose instead a DTI registration algorithm that leverages full tensor information to drive improved alignment. This proposed pipeline is evaluated against the standard FA-based approach using a DTI dataset from an ongoing study of Alzheimer's disease (AD). The dataset consists of subjects scanned at two time points and at each time point the DTI acquisition consists of two back-to-back repeats in the same scanning session. The repeated scans allow us to evaluate the specificity of each pipeline, using a test-retest design, and assess precision, using bootstrap-based method. The results show that the tensor-based pipeline achieves both higher specificity and precision than the standard FA-based approach. Tensor-based registration for longitudinal processing of DTI data in clinical studies may be of particular value in studies assessing disease progression.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Brain Mapping/ methods;Diffusion Tensor Imaging/ methods;Disease Progression;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Longitudinal Studies;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Reproducibility of Results;Sensitivity and Specificity","Keihaninejad, S.;Zhang, H.;Ryan, N. S.;Malone, I. B.;Modat, M.;Cardoso, M. J.;Cash, D. M.;Fox, N. C.;Ourselin, S.",2013,May 15,10.1016/j.neuroimage.2013.01.044,0,
3417,The importance of group-wise registration in tract based spatial statistics study of neurodegeneration: a simulation study in Alzheimer's disease,"Tract-based spatial statistics (TBSS) is a popular method for the analysis of diffusion tensor imaging data. TBSS focuses on differences in white matter voxels with high fractional anisotropy (FA), representing the major fibre tracts, through registering all subjects to a common reference and the creation of a FA skeleton. This work considers the effect of choice of reference in the TBSS pipeline, which can be a standard template, an individual subject from the study, a study-specific template or a group-wise average. While TBSS attempts to overcome registration error by searching the neighbourhood perpendicular to the FA skeleton for the voxel with maximum FA, this projection step may not compensate for large registration errors that might occur in the presence of pathology such as atrophy in neurodegenerative diseases. This makes registration performance and choice of reference an important issue. Substantial work in the field of computational anatomy has shown the use of group-wise averages to reduce biases while avoiding the arbitrary selection of a single individual. Here, we demonstrate the impact of the choice of reference on: (a) specificity (b) sensitivity in a simulation study and (c) a real-world comparison of Alzheimer's disease patients to controls. In (a) and (b), simulated deformations and decreases in FA were applied to control subjects to simulate changes of shape and WM integrity similar to what would be seen in",,"Keihaninejad, S.;Ryan, N. S.;Malone, I. B.;Modat, M.;Cash, D.;Ridgway, G. R.;Zhang, H.;Fox, N. C.;Ourselin, S.",2012,,,0,
3418,Fornix White Matter is Correlated with Resting-State Functional Connectivity of the Thalamus and Hippocampus in Healthy Aging but Not in Mild Cognitive Impairment - A Preliminary Study,"In this study, we wished to examine the relationship between the structural connectivity of the fornix, a white matter (WM) tract in the limbic system, which is affected in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease, and the resting-state functional connectivity (FC) of two key related subcortical structures, the thalamus, and hippocampus. Twenty-two older healthy controls (HC) and 18 older adults with aMCI underwent multi-modal MRI scanning. The fornix was reconstructed using constrained-spherical deconvolution-based tractography. The FC between the thalamus and hippocampus was calculated using a region-of-interest approach from which the mean time series were exacted and correlated. Diffusion tensor imaging measures of the WM microstructure of the fornix were correlated against the Fisher Z correlation values from the FC analysis. There was no difference between the groups in the fornix WM measures, nor in the resting-state FC of the thalamus and hippocampus. We did however find that the relationship between functional and structural connectivity differed significantly between the groups. In the HCs, there was a significant positive association between linear diffusion (CL) in the fornix and the FC of the thalamus and hippocampus, however, there was no relationship between these measures in the aMCI group. These preliminary findings suggest that in aMCI, the relationship between the functional and structural connectivity of regions of the limbic system may be significantly altered compared to healthy ageing. The combined use of diffusion weighted imaging and functional MRI may advance our understanding of neural network changes in aMCI, and elucidate subtle changes in the relationship between structural and functional brain networks.",,"Kehoe, E. G.;Farrell, D.;Metzler-Baddeley, C.;Lawlor, B. A.;Kenny, R. A.;Lyons, D.;McNulty, J. P.;Mullins, P. G.;Coyle, D.;Bokde, A. L.",2015,,10.3389/fnagi.2015.00010,0,
3419,MRI diagnosis of gliomatosis cerebri,"Until recently the diagnosis of gliomatosis cerebri has been made on postmortem examination. This article reviews the use of serial magnetic resonance imaging studies to suggest premorbid diagnosis of this condition. The following is a case report of a 14-year-old female who had a subtotal cortical resection of tumor and several years later developed a progressive dementia. At postmortem examination the diagnosis of gliomatosis cerebri was made. Diffuse progressive white matter changes involving both hemispheres and brainstem, with increased thickness of the corpus callosum and without changes in cortical markings on T(2)-weighted magnetic resonance images, in this patient were highly suggestive of the diagnosis of gliomatosis cerebri.",,"Keene, D. L.;Jimenez, C.;Hsu, E.",1999,February,,0,
3420,Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS,"Background: Leukoencephalopathy with neuroaxonal spheroids is a rare cause of severe, sub-acute dementia that usually presents in childhood and is inherited in an autosomal dominant pattern. The authors present clinical, radiologic, and pathologic features of adult-onset, sporadic cases mimicking cerebral-type progressive MS. Methods: Five patients referred to an MS subspecialty clinic from 1999 to 2006 suspected of having primary cerebral MS. All patients were reviewed clinically, radiologically, and pathologically at Mayo Clinic Rochester. Diagnostic brain biopsies were examined by two neuropathologists. Results: All patients had severe, progressive cognitive and motor impairment, often with prominently asymmetrical features and diffuse nonenhancing subcortical white matter lesions on brain MRI. Cerebrovascular and spinal cord imaging were normal. CSF showed elevated neuron-specific enolase without elevated oligoclonal bands or IgG index. Extensive evaluations for alternative diagnoses were unrevealing. Pathologic examination confirmed leukodystrophy with neuroaxonal spheroids and pigmented glia on all patients. Therapies initiated did not alter the severe progressive disease course. Conclusions: Leukoencephalopathy with neuroaxonal spheroids occurs sporadically, in adults, and mimics cerebral-type MS or other leukodystrophies. Brain biopsy may be diagnostic in life; however, no treatment is known to be effective. Pathologic diagnosis is important to avoid potentially toxic therapies aimed at CNS inflammatory diseases such as MS. Copyright © 2008 by AAN Enterprises, Inc.",,"Keegan, B. M.;Giannini, C.;Parisi, J. E.;Lucchinetti, C. F.;Boeve, B. F.;Josephs, K. A.",2008,March,,0,
3421,Prevalence and cognitive impact of medial temporal atrophy in a hospital stroke service: retrospective cohort study,"BACKGROUND: Cerebrovascular disease and neurodegeneration cause cognitive impairment and frequently coexist. AIMS: Our objectives were to investigate the prevalence and cognitive impact of medial temporal lobe atrophy - a radiological marker often associated with Alzheimer's disease - in a hospital stroke service. METHODS: Retrospective cohort study of patients from a hospital stroke service. Patients assessed for suspected ischemic stroke or transient ischemic attack, irrespective of final diagnosis, underwent neuropsychological testing and magnetic resonance imaging. medial temporal lobe atrophy, white matter hyperintensities, lacunes, and cerebral microbleeds were rated using established criteria and validated scales. The associations between medial temporal lobe atrophy and cognition were tested using multivariable logistic regression analyses, adjusted for age and imaging markers of cerebrovascular disease. RESULTS: Three hundred and ninety-three patients were included, of whom 169 (43%; 95% confidence interval: 38.1-48.1%) had medial temporal lobe atrophy; in 38 patients (9.7%), medial temporal lobe atrophy was severe (mean score >/=2). In unadjusted logistic regression analyses in the whole cohort, mean medial temporal lobe atrophy score was associated with verbal memory, nominal and perceptual skills, executive function, and speed and attention. After adjustment for age, white matter hyperintensities, number of lacunes, presence of cerebral microbleeds, previous ischemic stroke or transient ischemic attack, and premorbid intelligence quotient, mean medial temporal lobe atrophy score remained associated with impairment in verbal memory (odds ratio: 1.64; 95% confidence interval 1.04-2.58) and nominal skills (odds ratio: 1.61; 95% confidence interval 1.04-2.48). CONCLUSIONS: Medial temporal lobe atrophy is common and has an independent impact on cognitive function in a stroke service population, independent of confounding factors including age and magnetic resonance imaging markers of cerebrovascular disease. Medial temporal lobe atrophy is independently related to verbal memory and nominal skills, while small vessel pathology also contributes to speed and attention, and executive and perceptual functions.",,"Kebets, V.;Gregoire, S. M.;Charidimou, A.;Barnes, J.;Rantell, K.;Brown, M. M.;Jager, H. R.;Cipolotti, L.;Werring, D. J.",2015,Aug,10.1111/ijs.12544,0,
3422,Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints,"BACKGROUND AND PURPOSE: Arterial stiffening and thickening and endothelial dysfunction may be associated with cognitive decline or white matter hyperintensities (WMH) independently of blood pressure level. We aimed to investigate, using an integrative approach, the relative contributions of structural and functional vascular factors to the degree of cognitive impairment (primary outcome) and the severity of WMH (secondary outcome) in elderly hypertensive patients with subjective memory complaints, a group prone to dementia. METHODS: A prospective, dedicated, cross-sectional population of 198 elderly hypertensive patients (mean age 69.3+/-6.2 years) with subjective memory complaints underwent a full set of cognitive function assessments, brain MRI with semiquantification of WMH, carotid ultrasonography, carotid-femoral pulse wave velocity, brachial endothelial function, and plasma von Willebrand Factor measurements. RESULTS: After adjustment for the usual cardiovascular risk factors, increased arterial stiffness (as assessed by pulse wave velocity) was significantly and independently associated with memory impairment in men. The severity of WMH was independently associated with increased carotid intima media thickness and stiffness (as assessed by augmentation index) as well as with increased age and plasma levels of von Willebrand Factor, a biomarker of endothelial dysfunction. CONCLUSIONS: Our data suggest that vascular abnormalities, independently of blood pressure levels, may play a role in the setting of subjective memory complaints as well as of WMH in elderly hypertensive patients. Arterial thickness and stiffness as well as endothelial function should be assessed simultaneously and may represent additional targets for the prevention of subjective memory complaints and WMH.","Aged;Aged, 80 and over;Carotid Artery Diseases/pathology;Cerebrovascular Circulation;Cognition Disorders/epidemiology/pathology/physiopathology;Cross-Sectional Studies;Endothelium, Vascular/pathology/physiology;Female;Humans;Hypertension/*epidemiology/*pathology/physiopathology;Leukoaraiosis/*epidemiology/*pathology/physiopathology;Magnetic Resonance Imaging;Male;Memory Disorders/*epidemiology/*pathology/physiopathology;Middle Aged;Nerve Fibers, Myelinated/pathology;Prevalence;Prospective Studies;Pulsatile Flow;Risk Factors;Severity of Illness Index","Kearney-Schwartz, A.;Rossignol, P.;Bracard, S.;Felblinger, J.;Fay, R.;Boivin, J. M.;Lecompte, T.;Lacolley, P.;Benetos, A.;Zannad, F.",2009,Apr,10.1161/strokeaha.108.532853,0,
3423,Tensor diffusion imaging in B(12) leukoencephalopathy,"Anisotropy measurements were obtained from periventricular foci of T2 prolongation and adjacent normal-appearing white matter in a case of B(12) leukoencephalopathy. Measurements were compared with mean values from two age-matched control subjects. Anisotropy was greatly reduced in the lesions evident on T2-weighted images and in the normal-appearing adjacent white matter (WM), indicating that the extent of WM tract disruption was greater than could be identified on routine MR sequences.",,"Kealey, S. M.;Provenzale, J. M.",2002,November/December,,0,
3424,"Vascular risk factors, brain infarcts and nonspecific white matter lesions","Nonspecific white matter lesions are often seen on MR scans of elderly people. The purpose of present article is to examine the potential relationship between MR detected nonspecific white matter lesions, vascular risk factors and different type of brain infarcts. Our study group consisted of 89 male and female aged from 28 to 90 with history of cerebrovascular risk factors and no dementia. Nonspecific white matter lesions were found in 49 (55%). Clinical data retrieved from the patient files included age, sex, presence of hypertension, presence of diabetes mellitus and presence of vascular disease (defined as a history of angina pectoris, myocardial infarction, congestive heart failure, intermittent claudi-cation or vascular surgery). Patients with vascular cognitive impairment and nonspecific white matter lesions were vastly older than these free of lesions (t-test P=0.001). History of hypertension we founded in 81.6% in patients with lesions and 62.5% without lesions (t-test P=0.043). Patients with white matter lesions more often presented with lacunar brain infarcts (t-test P=0.0002). Analyses of other factors exhibited that no significant difference was found in the distribution of diabetes mellitus, angina pectoris, myocardial infarction, congestive heart failure and valvular disease among groups with and without lesions. Left ventricular hypertrophy, ischemic ST-T patterns and dysrhythmia on electrocardiograms were also not significantly associated with white matter lesions. Our results confirm that development of white matter lesions correlated vastly with age, hypertension and lacunar brain infarcts.",adult;aged;angina pectoris;article;brain infarction;cerebrovascular disease;congestive heart failure;dementia;diabetes mellitus;electrocardiogram;female;heart arrhythmia;heart infarction;heart left ventricle hypertrophy;human;hypertension;intermittent claudication;major clinical study;male;nuclear magnetic resonance imaging;risk factor;ST segment;valvular heart disease;vascular disease;vascular surgery;white matter,"Kazakov, D.",2005,,,0,
3425,Computer-aided evaluation method of white matter hyperintensities related to subcortical vascular dementia based on magnetic resonance imaging,"It has been reported that the severity of subcortical vascular dementia (VaD) correlated with an area ratio of white matter hyperintensity (WMH) regions to the brain parenchyma (WMH area ratio). The purpose of this study was to develop a computer-aided evaluation method of WMH regions for diagnosis of subcortical VaD based on magnetic resonance (MR) images. A brain parenchymal region was segmented based on the histogram analysis of a T1-weigthed image. The WMH regions were segmented on the subtraction image between a T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images using two segmentation methods, i.e., a region-growing technique and a level-set method, which were automatically and adaptively selected on each WMH region based on its image features by using a support vector machine. We applied the proposed method to 33 slices of the three types of MR images with 245 lesions, which were acquired from 10 patients (age range: 64-90 years, mean: 78) with a diagnosis of VaD on a 1.5-T MR imaging scanner. The average similarity index between regions determined by a manual method and the proposed method was 93.5+/-2.0% for brain parenchymal regions and 78.2+/-11.0% for WMH regions. The WMH area ratio obtained by the proposed method correlated with that determined by two neuroradiologists with a correlation coefficient of 0.992. The results presented in this study suggest that the proposed method could assist neuroradiologists in the evaluation of WMH regions related to the subcortical VaD.","Algorithms;Dementia, Vascular/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/ pathology;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic","Kawata, Y.;Arimura, H.;Yamashita, Y.;Magome, T.;Ohki, M.;Toyofuku, F.;Higashida, Y.;Tsuchiya, K.",2010,Jul,10.1016/j.compmedimag.2009.12.014,0,
3426,Creutzfeldt-Jakob disease with congophilic kuru plaques: CT and pathological findings of the cerebral white matter,"In a patient whose Creutzfeldt-Jakob disease with congophilic kuru plaques that was proved at necropsy, the early brain CT showed low-density areas in the cerebral white matter before cortical atrophy and ventricular enlargement became apparent. Subsequently, there occurred diffuse white matter lucency and severe brain atrophy. At necropsy, there was severe white matter destruction which was more prominent than cortical neuronal loss. Serial CT scans were of great value for demonstrating the early and predominant changes in the cerebral white matter.",adult;article;autopsy;brain atrophy;case report;computer assisted tomography;Creutzfeldt Jakob disease;female;human;human tissue;kuru;nerve cell lesion;neuropathology;priority journal;white matter,"Kawata, A.;Suga, M.;Oda, M.;Hayashi, H.;Tanabe, H.",1992,,,0,
3427,Retinal microvascular signs and 10-year risk of cerebral atrophy: the Atherosclerosis Risk in Communities (ARIC) study,"BACKGROUND AND PURPOSE: Cerebral atrophy, detected as ventricular enlargement or sulcal widening on MRI, is recognized as a risk factor for vascular dementia or Alzheimer disease. However, its underlying pathophysiology is not known. We examined whether retinal microvascular assessment could provide predictive information on the risk of ventricular enlargement and sulcal widening on MRI. METHODS: A prospective, population-based study was conducted of 810 middle-aged persons without clinical stroke or MRI infarcts. All participants had a first cranial MRI and retinal photography in 1993 to 1995 and returned for a repeated MRI in 2004 to 2006 (median follow-up of 10.5 years). Retinal photographs were graded for presence of retinopathy and retinal microvascular abnormalities, and MRI images were graded for ventricular size and sulcal size according to standardized protocols. Ventricular enlargement and sulcal widening were defined as an increase in ventricular size or sulcal size of >or=3 of 10 grades between baseline and follow-up. RESULTS: After adjusting for age, gender, and cardiovascular risk factors, retinopathy and arteriovenous nicking at baseline were associated with 10-year ventricular enlargement (OR and 95% CI: 2.03, 1.20 to 4.42 for retinopathy and 2.19, 1.23 to 3.90 for arteriovenous nicking). Retinal signs were not associated with 10-year sulcal widening. CONCLUSIONS: Retinopathy and arteriovenous nicking are predictive of long-term risk of ventricular enlargement, but not of sulcal widening, independent of cardiovascular risk factors. These data support a microvascular etiology for subcortical but not cortical cerebral atrophy.",Atherosclerosis/complications/ pathology;Atrophy/complications/pathology;Cerebral Cortex/ pathology;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Microvessels/pathology;Middle Aged;Predictive Value of Tests;Prospective Studies;Retinal Diseases/complications/ pathology;Retinal Vessels/ pathology;Risk;Risk Assessment,"Kawasaki, R.;Cheung, N.;Mosley, T.;Islam, A. F.;Sharrett, A. R.;Klein, R.;Coker, L. H.;Knopman, D. S.;Shibata, D. K.;Catellier, D.;Wong, T. Y.",2010,Aug,10.1161/strokeaha.110.585042,0,
3428,Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping,"OBJECTIVE: In clinical cerebral 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) studies, we sometimes encounter hyperglycemic patients with diabetes mellitus or patients who have not adhered to the fasting requirement. The objective of this study was to investigate the influence of mild hyperglycemia (plasma glucose range 110-160 mg/dl) on the cerebral FDG distribution patterns calculated by statistical parametric mapping (SPM). METHODS: We studied 19 healthy subjects (mean age 66.2 years). First, all the subjects underwent FDG-PET scans in the fasting condition. Then, 9 of the 19 subjects (mean age 64.3 years) underwent the second FDG-PET scans in the mild hyperglycemic condition. The alterations in the FDG-PET scans were investigated using SPM-and region of interest (ROI)-based analyses. We used three reference regions: (1) SPM global brain (SPMgb) used for SPM global mean calculation, (2) the gray and white matter region computed from magnetic resonance image (MRIgw), and (3) the cerebellar cortex (Cbll). RESULTS: The FDG uptake calculated as the standardized uptake value (average) in SPMgb, MRIgw, and Cbll regions in the mild hyperglycemic condition was 42.7%, 41.3%, and 40.0%, respectively, of that observed in the fasting condition. In SPM analysis, the mild hyperglycemia was found to affect the cerebral distribution patterns of FDG. The FDG uptake was relatively decreased in the gray matter, mainly in the frontal, temporal, and parietal association cortices, posterior cingulate, and precuneus in both SPMgb-and MRIgw-reference-based analyses. When Cbll was adopted as the reference region, those decrease patterns disappeared. The FDG uptake was relatively increased in the white matter, mainly in the centrum semiovale in all the reference-based analyses. CONCLUSIONS: It is noteworthy that the FDG distribution patterns were altered under mild hyperglycemia in SPM analysis. The decreased uptake patterns in SPMgb-(SPM default) and MRIgw-reference-based analyses resembled those observed in Alzheimer's disease. Under mild hyperglycemia, we can recommend Cbll as the reference region to detect decreased uptake patterns. We should pay special attention to controlling the diet condition, monitoring hyperglycemia, and optimizing the reference region in SPM analysis, particularly in the diagnosis of early Alzheimer's disease in clinical FDG-PET.","Aged;Blood Glucose/analysis/metabolism;Brain/ metabolism/ radionuclide imaging;Data Interpretation, Statistical;Female;Fluorodeoxyglucose F18/ pharmacokinetics;Humans;Hyperglycemia/ metabolism;Imaging, Three-Dimensional/methods;Magnetic Resonance Imaging;Male;Middle Aged;Pattern Recognition, Automated;Positron-Emission Tomography;Radiopharmaceuticals/pharmacokinetics;Reference Standards;Signal Processing, Computer-Assisted;Stereotaxic Techniques;Tissue Distribution","Kawasaki, K.;Ishii, K.;Saito, Y.;Oda, K.;Kimura, Y.;Ishiwata, K.",2008,Apr,10.1007/s12149-007-0099-7,0,
3429,"Epidemiologic and clinico-pathologic study on senile dementia in a Japanese community, Hisayama","To elucidate a definite prevalence of dementia and its risk factors in the senescence, 887 subjects aged 65 years or over of Hisayama residents (94.6% of the whole population in the same age-range) were examined from May to December, 1985, as to whether he or she has suffered dementia. Karasawa's ""Clinical criteria for the severity of dementia"", Hasegawa's Dementia Scale and Hachinski's ischemic score were used as a procedure to identify demented persons. Out of 887 examined, 59 subjects were diagnosed to have had dementia (6.7%) with female to male ratio being 1.2. The prevalence rates of dementia increased with advanced age decades and sharply grew up over tha age of 80 years. Brain morphology in 50 of the 59 dementias was re-evaluated by autopsy and/or CT scan, during a 55-month follow-up period from January 1986 to July 1990. Coincidence rate between clinical evaluation and morphological diagnosis was 90.5% for vascular dementia (VD), 62.5% for senile dementia of Alzheimer type (SDAT), and 28.6% for other or ill-defined dementia (Others). Misdiagnosis of clinical evaluation for VD was mainly due to uncertain history of head trauma, while the subjects suffering from atypical stroke tended to be diagnosed as SDAT. Out of the 21 cases who were initially diagnosed as having other or ill-defined dementia, 8 were re-evaluated as VD, and 7 as SDAT later. Most cases who were finally diagnosed as having VD had multi-infarcts without an episode of stroke attack, while those who were classified to SDAT had less severely undergone dementia. The final type-specific prevalence of dementia was 56% for VD, 26% for SDAT and 18% for Others, respectively. The ratio of VD to SDAT was 2.2, indicating more frequent VD than SDAT. Retrospective case-control study on risk factors of VD was performed using selected parameters obtained at examinations in 1973 or 1978, comparing 27 VD cases and 789 non-demented cases. As a consequence, aging, hypertension, electro-cardiographic abnormalities (Minnesota code 3-1 and/or 4-1, 2, 3) and high hematocrit were taken as important risk factors for VD. These risk factors were very similar to those for lacunar infarcts among Hisayama residents. The difficulty of epidemiologic study on dementia in general population and the accuracy of diagnosis for type of dementia were discussed.",aged;Alzheimer disease;article;dementia;female;human;Japan;male;multiinfarct dementia;pathology;prevalence;risk factor,"Kawano, H.",1993,,,0,
3430,Improvement of dementia after STA-MCA anastomosis for major cerebral artery occlusion: Report of two cases and surgical indication,"We report 2 cases with occlusive cerebrovascular disease in which superficial temporal artery-middle cerebral artery (STA-MCA) bypass apparently improved the dementia. The first patient, a 65-year-old male, complained of transient weakness of the left extremities and was of dementia with the total intelligence quotient (IQ) of 74. The neuroimages showed occlusion of the internal carotid artery and watershed cerebral infarction on the right side. Single photon emission computed tomography (SPECT) revealed decreased cerebral blood flow (CBF) at rest and impaired acetazolamide reactivity in the affected hemisphere. After the right STA-MCA anastomosis, the cognitive function improved gradually in accordance with increasing CBF. The total IQ recovered to 84 in eight months after the operation. The second patient was a 61-year-old female complaining of transient right motor weakness and aphasia. Her total IQ was decreased to 76 without no infarction on CT scan. Angiography demonstrated left MCA occlusion, and SPECT study showed decreased resting CBF and impaired acetazolamide reactivity in the left cerebral hemisphere. After the left STA-MCA anastomosis, her clinical symptoms and cognitive function improved markedly in accordance with increasing CBF. The total IQ increased to 84 in four months after the operation. The results of our cases and other reports suggest that dementia due to hemodynamic insufficiency would be treatable if surgical revascularization is performed in early phase of the condition.",acetazolamide;adult;aged;aphasia;article;brain angiography;brain blood flow;brain infarction;case report;clinical feature;computer assisted tomography;dementia;female;hemodynamic monitoring;human;image analysis;intelligence quotient;male;muscle weakness;occlusive cerebrovascular disease;revascularization;single photon emission computer tomography;treatment indication,"Kawanishi, M.;Kajikawa, H.;Yamamura, K.;Nomura, E.;Sugie, A.;Kajikawa, M.;Hihara, R.;Nagasawa, S.",1999,,,0,
3431,Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy,"Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ϵ4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.",apolipoprotein E4;C reactive protein;creatinine;glucose;hemoglobin A1c;high density lipoprotein cholesterol;intercellular adhesion molecule 1;interleukin 6;low density lipoprotein cholesterol;triacylglycerol;tumor necrosis factor;aged;albuminuria;article;blood sampling;brain atrophy;brain infarction;cerebrospinal fluid;cerebrovascular disease;cholesterol blood level;chronic kidney disease;cognition;cognitive defect;cognitive function test;computer analysis;controlled study;creatinine blood level;diabetic patient;diabetic retinopathy;disease duration;disease severity;female;follow up;Geriatric Depression Scale;glomerulus filtration rate;glucose blood level;hippocampal atrophy;hippocampus;human;kidney failure;longitudinal study;major clinical study;male;memory disorder;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;priority journal;triacylglycerol blood level;voxel based morphometry;waist circumference;white matter lesion;word recognition,"Kawamura, T.;Umemura, T.;Umegaki, H.;Imamine, R.;Kawano, N.;Mase, H.;Mizoguchi, A.;Minatoguchi, M.;Kusama, M.;Kouchi, Y.;Watarai, A.;Kanai, A.;Nakashima, E.;Hotta, N.",2016,,,0,
3432,Soluble adhesion molecules and C-reactive protein in the progression of silent cerebral infarction in patients with type 2 diabetes mellitus,"The purpose of this study was to investigate the association between the progression of silent cerebral infarction (SCI) and levels of soluble adhesion molecules and high-sensitivity C-reactive protein (hs-CRP) in type 2 diabetic patients. One hundred twenty middle-aged and elderly diabetic patients without histories of vascular events were followed up for a period of 3 years. We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, E-selectin, and hs-CRP and assessed brain ischemic lesions by magnetic resonance imaging at baseline and 3 years later. Silent cerebral infarction was observed in 13% of the patients at baseline, and these patients were significantly older and had significantly higher blood pressure than those without SCI. Thirty-two patients had newly diagnosed SCI after 3 years. There were no significant differences in factors such as age, blood pressure, and diabetic control between patients without SCI and those in whom it was newly diagnosed. However, only sICAM-1 levels, but not the other soluble adhesion molecules or hs-CRP, were associated with the progression of SCI, and this relationship remains after adjustment for risk factors. On the other hand, higher levels of sICAM-1 and hs-CRP at baseline were observed in 7 patients who were excluded from the present study because of the onset of symptomatic cerebral infarction during follow-up. Our present study suggests that sICAM-1 levels may be a potential marker for SCI, which may lead to future stroke and vascular dementia, and that this marker could be useful in monitoring disease progression and as a surrogate marker in treatment studies. © 2006 Elsevier Inc. All rights reserved.",,"Kawamura, T.;Umemura, T.;Kanai, A.;Nagashima, M.;Nakamura, N.;Uno, T.;Nakayama, M.;Sano, T.;Hamada, Y.;Nakamura, J.;Hotta, N.",2006,April,,0,
3433,Diffuse cerebral white matter lesion on MRI in a patient with late onset DRPLA without dementia,,article;brain injury;dentatorubropallidoluysian atrophy;diagnostic imaging;human;nuclear magnetic resonance imaging;white matter,"Kawamura, T.",1999,,,0,
3434,Leuko-Araiosis and cerebral hypoperfusion compared between patients with ischemic vascular dementia and normal elderly volunteers,"Lesions in white matter of unknown origin among the elderly have been of interest for many years, and their pathogenesis and clinical significance need clarification. Local cerebral blood flow was measured among patients with ichemic vascular dementia (IVD, n = 38) and compared with age-matched normal volunteers (n = 18) utilizing xenon-enhanced computed tomography (CT). Volume ratios for total leuko-araiosis, as well as volume ratios for apparently normal white and gray matter, were determined by plain, noncontrasted CT densitometry throughout slices of brain examined later during stable xenon inhalation enabling perfusion values for each compartment to be compared. Volume ratios for total leuko-araiosis to total brain parenchyma were twice as large among patients with IVD (12.0 +/- 5.6%) compared with elderly normal volunteers (6.0 +/- 2.7%). However, cerebral perfusion values within regions of leuko-araiosis compared to""normal"" white matter were decreased to the same degree among patients with IVD (14 +/- 6 ml/100 g brain/min) and among elderly normal volunteers with leuko-araiosis (13 +/- 5). Local cerebral blood flow values were reduced for all regions of brain examined among IVD patients compared with age-matched normals. Among patients with IVD, multiple regression analyses correlated increased volumes of leuko-araiosis with (a) advancing age, (b) hypertension, and (c) reduced perfusion in vascular territories supplying the putamen. Hypoperfusion within deep cerebral territories correlates with pathogenesis of leuko-araiosis among patients with ischemic vascular dementia.",,"Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1992,,10.1016/s1052-3057(10)80042-4,0,
3435,Leuko-araiosis and cerebral hypoperfusion compared in elderly normals and Alzheimer's dementia,"OBJECTIVE: To elucidate the pathogenesis of leuko-araiosis in patients with Alzheimer's disease by utilizing CT densitometry of the brain and measurements of local perfusion in order to quantify the extent of leuko-araiosis and local hypoperfusion compared with similar measurements made among age-matched normal volunteers. DESIGN: Cross-sectional case-control study. SETTING: Out-patient visits to a specialized laboratory located in a large hospital facility. PATIENTS: Eighteen elderly patients with probable dementia of Alzheimer type (DAT, aged 71.8 +/- 5.1 years) and 17 neurologically and cognitively normal, age-matched volunteers (aged 68.2 +/- 9.6 years) were admitted to the study according to established criteria. INTERVENTION: None MAIN OUTCOME MEASURES: Cerebral blood flow (mL/100 g brain/min) estimated by the xenon inhalation CT-CBF method correlated with volume percentage ratio (%) measured by CT densitometry for leuko-araiosis, compared to normal white and gray matter. RESULTS: Perfusion values for frontal and occipital white matter as well as frontal, parietal, temporal, and occipital cortex were all decreased in DAT patients. Ratios for leuko-araiosis to total brain tissue volumes were greater among patients with DAT compared with age-matched normal volunteers. White matter perfusion in zones of leuko-araiosis was decreased to a similar degree in both DAT and elderly normal volunteers. CONCLUSIONS: Perfusion is reduced to the same degree in regions of leuko-araiosis in elderly normals as in DAT patients, but the extent of leuko-araiosis is greater among DAT patients and presumably contributes to cognitive impairments.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/diagnosis;Atrophy;Blood Flow Velocity;Brain Ischemia/epidemiology/*pathology/radiography;Case-Control Studies;*Cerebrovascular Circulation;Cerebrovascular Disorders/epidemiology/etiology;Cross-Sectional Studies;Female;Humans;Intelligence Tests;Male;Middle Aged;Risk Factors;Tomography, X-Ray Computed;Xenon","Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1992,Apr,,0,
3436,Cerebral hypoperfusion correlates with mild and parenchymal loss with severe multi-infarct dementia,"Relative contributions of two potential pathogenetic factors for cognitive impairments among patients with multi-infarct dementia (MID) are reported. Cognitive test scores were correlated with measures of cerebral hypoperfusion and loss of brain parenchyma. Local cerebral blood flow values were determined utilizing stable xenon contrasted computed tomography and volumes for brain parenchyma were estimated from ratios of volumes of infarcted brain plus cerebrospina1 fluid/total intracranial volume measured on the same CT slices among two groups of patients, one with mild and the other with severe MID. A total of 26 demented patients with multiple cerebral infarcts were divided into 2 index groups, one with mild and the other with severe MID (mild MID, CCSE ≥ 15, n = 16; severe MID, CCSE < 15, n = 10). Results were compared with similar measures among age-matched neurologically normal volunteers (n = 14). Ratios for volumes of lost brain parenchyma were significantly higher among severe MID patients than among age-matched normal volunteers, whereas estimates of brain loss among patients with mild MID did not differ from elderly normal volunteers. In patients with mild MID, LCBF values for cortical gray matter were decreased compared with age-matched normal volunteers. Results suggest that chronic cerebral hypoperfusion is an important determinant for mild dementia among patients in the early stages of MID, but volumes of lost cerebral parenchyma due to cerebral infarctions is an important determinant for advanced stages of MID.",adult;aged;article;brain blood flow;brain infarction;clinical article;female;human;male;multiinfarct dementia;perfusion;priority journal,"Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1991,,,0,
3437,Cerebral white matter perfusion in dementia of Alzheimer type,"Local cerebral blood flow was measured in 19 patients with probable dementia of Alzheimer type (DAT) by using xenon-enhanced computerized tomography (CT) and CT densitometry to accurately differentiate white from gray matter. Patients met standard diagnostic criteria for probable DAT and results were compared with similar measures in 26 age-matched, neurologically and cognitively normal volunteers. Perfusions of frontal and occipital white matter as well as frontal, parietal, temporal, and occipital cortex were reduced in DAT compared with age-matched normals. White matter perfusion differences were not observed among DAT patients with and without risk factors for stroke. Reduced perfusion of frontal white matter correlated significantly with reduced perfusion of thalamus and putamen in patients with DAT. Results confirm the frequent association of white matter abnormalities in patients with DAT that are possibly caused by amyloid angiopathy and may contribute to cognitive impairments.","Aged;Alzheimer Disease/*diagnosis/physiopathology;*Cerebrovascular Circulation;Female;Frontal Lobe/blood supply;Humans;Male;Putamen/blood supply;Thalamus/blood supply;*Tomography, X-Ray Computed;Xenon","Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1991,Winter,,0,
3438,Longitudinal measurement of cerebral perfusion in patients with multi-infarct dementia,"Longitudinal measurements of local cerebral blood flow (LCBF) were performed in 13 patients with multi-infarct dementia (MID) utilizing the xenon-enhanced computed tomography-CBF method. Subjects were divided into two groups: a group consisting of five patients with MID who deteriorated (aged 60.6 +/- 5.3 years) and whose CCSE scores decreased and a stable group comprised of eight patients (aged 64.5 +/- 4.5 years) whose CCSE scores did not change. Mean intervals between first and second LCBF measurements were 663 +/- 182 days for the deteriorated group and 795 +/- 495 days for the stable group. In the deteriorated group, LCBF values for frontal cortex, thalamus, and frontal white matter had declined further at the second measurement. In the stable group, LCBF values were not uniformly stable, but there were no overall mean decreases. The annual rate of decline among patients who deteriorated for frontal cortex, thalamus, and frontal white matter exceeded annual declines measured in elderly normal volunteers. Results suggest that progressive cerebral hypoperfusion contributes to cognitive declines in mild MID, but, if cerebral perfusion of frontal lobes and basal ganglia can become stabilized, further cognitive deterioration can be prevented.",,"Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1991,,10.1016/s1052-3057(10)80017-5,0,
3439,Leukoaraiosis correlates with cerebral hypoperfusion in vascular dementia,"Leukoaraiosis quantified by computerized densitometric measurements of reduced Hounsfield numbers was correlated with local cerebral blood flow on the same computed tomographic images of 35 patients with multi-infarct dementia and 16 age-matched elderly normal volunteers. The ratio for area of frontal leukoaraiosis to total area of parenchyma among the patients was significantly greater than that among the normal volunteers (5.8 +/- 2.3% compared with 3.1 +/- 1.3%, p less than 0.001). Severity of leukoaraiosis around the frontal horns of the lateral ventricles correlated significantly with severity of leukoaraiosis of the centrum semiovale adjacent to the bodies of the lateral ventricles. Cerebral blood flow values for all representative cerebral regions except the parietal white matter were reduced among the patients compared with the normal volunteers. Multivariate regression analysis revealed that reduced cerebral perfusion in the putamen and thalamus correlated significantly with the severity of leukoaraiosis. Cerebral hypoperfusion in territories supplied by deep penetrating arteries may contribute to the pathogenesis of leukoaraiosis.","Adult;Aged;Aged, 80 and over;Brain/ blood supply/radionuclide imaging;Brain Diseases/ physiopathology/radionuclide imaging;Cerebrovascular Circulation;Dementia, Vascular/ physiopathology/radionuclide imaging;Female;Humans;Male;Middle Aged;Tomography, Emission-Computed","Kawamura, J.;Meyer, J. S.;Terayama, Y.;Weathers, S.",1991,May,,0,
3440,Correlations of leuko-araiosis with cerebral atrophy and perfusion in elderly normal subjects and demented patients,"CT images of leuko-araiosis in brain slices were quantified according to volumes of reduced Hounsfield units in frontal periventricular white matter in groups of elderly patients with multi-infarct dementia (MID, n = 23) and dementia of the Alzheimer type (DAT, n = 16). Volumes of leuko-araiosis, estimates of atrophic cerebral tissue, and local cerebral perfusion utilising inhalation of xenon gas as the indicator were correlated on the same CT slices. Ratios of frontal leuko-araiosis to total brain tissue volume were similar for patients with MID and DAT (mean 5.7 (SD 2.1)% v 6.5 (3.2%)), and both were significantly greater than ratios in elderly normal volunteers (3.1(1.3)%, 0 < 0.001). Cerebral atrophy (measured as the ratio of volumes of cerebrospinal fluid to total brain area) for DAT patients was 17.0 (6.7)%, which was greater than for MID patients (12.5 (5.4)%; p < 0.05) and both types of patients showed more cerebral atrophy than did age matched, elderly normal subjects. Cerebral perfusion was decreased in all regions measured in patients with MID and DAT compared with elderly normal subjects. Multi variate regression analyses correlated frontal leuko-araiosis with reductions of local cerebral blood flow in subcortical grey matter (p < 0.025) in patients with vascular dementia but not in those with DAT. These quantitative measures implicate decreased perfusion due to atherosclerosis in territories supplied by the deep penetrating cerebral arteries in the pathogenesis of leuko-araiosis in patients with vascular dementia, but suggest a different pathogenesis for leuko-araiosis in Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology;Atrophy;Brain/blood supply/ pathology;Cerebral Cortex/blood supply/pathology;Dementia, Multi-Infarct/diagnosis/ pathology;Female;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/ pathology;Male;Middle Aged;Regional Blood Flow/physiology;Tomography, X-Ray Computed","Kawamura, J.;Meyer, J. S.;Ichijo, M.;Kobari, M.;Terayama, Y.;Weathers, S.",1993,Feb,,0,
3441,Werner's syndrome associated with progressive subcortical vascular encephalopathy of the Binswanger type,"A 56-year-old woman with Werner's syndrome was admitted to our hospital because of intractable foot ulcer and malnutrition. She presented dementia consisting of childish behaviour, loss of intelligence, and severe amnesia. Brain CT revealed diffuse periventricular low density areas, and brain MRI also disclosed periventricular high intensity areas under T2-intensified conditions. These findings gave a diagnosis of progressive subcortical vascular encephalopathy of the Binswanger type, which seemed to be the cause of her dementia. She finally died of heart failure due to acute myocardial infarction. Mild to moderate demyelinization was found in the subcortical area of the autopsied cerebrum, confirming the clinical diagnosis. Generalized atherosclerosis characteristic of Werner's syndrome may have predisposed this patient to Binswanger's encephalopathy.",adult;article;Binswanger encephalopathy;case report;computer assisted tomography;dementia;demyelination;disease association;female;human;nuclear magnetic resonance imaging;Werner syndrome,"Kawamura, H.;Mori, S.;Murano, S.;Yokote, K.;Tamura, K.;Saito, Y.",1999,,,0,
3442,A family with hereditary diffuse leukoencephalopathy with spheroids caused by a novel c.2442 + 2T > C mutation in the CSF1R gene,"Clinical phenotypes of hereditary diffuse leukoencephalopathy with spheroids (HDLS), a familial progressive neurodegenerative disorder affecting the white matter of the brain, are heterogenous and may include behavioral and personality changes, memory impairment, parkinsonism, seizure, and spasticity. Thus, HDLS is frequently unrecognized and misdiagnosed. Heterozygous mutations located within the kinase domain of the gene encoding the colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor with key roles in development and innate immunity, have been shown in HDLS. These different gene mutations may be related to the various clinical phenotypes. We report here a newly identified family with HDLS harboring a mutation in the CSF1R gene. We examined clinical and neuropathological features in three members of this family. These patients presented with affective incontinence, memory impairment, and executive dysfunction at onset, and revealed nonfluent aphasia, parkinsonism, and seizure as the disease progressed. We identified a novel CSF1R splice site mutation (c.2442 + 2T > C) in intron 18 for two of the patients. MRI of these patients revealed progressive, frontotemporal-predominant, confluent leukoencephalopathy. We also observed severe myelin loss, axonal degeneration, and abundant axonal spheroids, astrocytes, and microglia in the cerebral white matter, consistent with HDLS neuropathological features. Additionally, we identified atypical neuropathological findings for HDLS, including neuronal loss and gliosis with ballooned neurons and central chromatolysis in the frontal cortex and hippocampus. This report provides further evidence for the clinical and neuropathological heterogeneity of HDLS.",anticonvulsive agent;cell surface receptor;colony stimulating factor 1 receptor;fluorodeoxyglucose f 18;myelin;unclassified drug;abnormal behavior;adult;aggression;akinetic mutism;Alzheimer disease;aphasia;article;astrocyte;ataxic aphasia;auditory hallucination;autopsy;behavior change;brain atrophy;case report;clinical assessment;clinical feature;cognitive defect;comprehension;convulsion;delusion;dementia;depression;disease course;disease duration;dysarthria;dysphagia;enteric feeding;epilepsy;executive function;familial disease;family health;finger tremor;frontal cortex;frontotemporal dementia;gait disorder;gene mutation;genetic disorder;genetic heterogeneity;genetic identification;gliosis;hereditary diffuse leukoencephalopathy with spheroid;hippocampus;human;immobility;incontinence;innate immunity;intron;leukodystrophy;leukoencephalopathy;male;medical history;memory disorder;microglia;middle aged;Mini Mental State Examination;motor neuron disease;muscle rigidity;muscle weakness;nerve fiber degeneration;neuropathology;nuclear magnetic resonance imaging;parkinsonism;persistent vegetative state;phenotypic variation;physical examination;pneumonia;positron emission tomography;priority journal;seizure;speech disorder;tumor spheroid;white matter,"Kawakami, I.;Iseki, E.;Kasanuki, K.;Minegishi, M.;Sato, K.;Hino, H.;Shibuya, K.;Fujisawa, K.;Higashi, S.;Akiyama, H.;Furuta, A.;Takanashi, M.;Li, Y.;Hattori, N.;Mitsuyama, Y.;Arai, H.",2016,,,0,
3443,"Non-persistent ""doll phenomenon"" in a patient with right thalamic infarction","An 81-year-old right-handed woman was admitted because of acute dysarthria and left hemiparesis. She had lived herself without aids until the admission. On neurological examination she was confused and disoriented. She was ambulant, but had mild dysarthria and mild left hemiparesis. Neuropsychological tests showed severe impairment of memory, mild impairment of visual cognition, decreased fluency of word recall and mild paramnesia, but no acalculia, agraphia, aphasia or apraxia. MRI of the brain showed small infarction in the right anterior thalamus. 123I-IMP SPECT demonstrated a decrease in CBF of the thalamus, basal ganglia, and frontal lobe on the right. During admission, she always played with a doll as if she took it as a real baby. This peculiar symptom, ""doll phenomenon"" continued for approximatoly three months later. The ""doll phenomenon"" usually appears in demented patients with diffuse mental deterioration or dysfunction of the frontal lobe. The present patient had not been demented until the onset of the thalamic infarction, and disturbance of cognition caused by the right thalamic infarction probably produced the ""doll phenomenon"".",inosine phosphate;iodine 123;aged;agraphia;aphasia;apraxia;article;basal ganglion;brain infarction;case report;clinical feature;cognitive defect;confusion;dementia;diagnostic imaging;disorientation;doll phenomenon;dysarthria;female;frontal lobe;hemiparesis;human;memory disorder;neurologic examination;neuropsychological test;nuclear magnetic resonance imaging;paramnesia;right thalamic infarction;single photon emission computer tomography;thalamus anterior nucleus;vision;word recognition,"Kawada, N.;Miyazaki, M.;Kuzuhara, S.",2002,,,0,
3444,Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment,"BACKGROUND: Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T2 relaxation time technique may serve as a more direct measure of myelin content. PURPOSE/HYPOTHESIS: The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment. POPULATION: The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33). FIELD STRENGTH/SEQUENCE ASSESSMENT: Long T2 , short T2 , and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants. STATISTICAL TESTS, RESULTS: AD patients displayed higher age-adjusted long and short T2 values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T2 /MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T2 and MWF values in these regions. DATA CONCLUSION: Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.",Alzheimer's disease;T2 relaxometry;depression;magnetic resonance imaging (MRI);memory;mild cognitive impairment,"Kavroulakis, E.;Simos, P. G.;Kalaitzakis, G.;Maris, T. G.;Karageorgou, D.;Zaganas, I.;Panagiotakis, S.;Basta, M.;Vgontzas, A.;Papadaki, E.",2017,Aug 31,,0,
3445,White matter integrity linked to functional impairments in aging and early Alzheimer's disease,"BACKGROUND: Alzheimer's disease (AD) is associated with changes in cerebral white matter (WM), but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. METHODS: Older adult control subjects (OA, n = 18) and mildly impaired AD patients (n = 14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity (D) maps for nine regions of interest in three brain regions that were then compared with the performance measures. RESULTS: AD patients exhibited nonsignificant trends toward lower FAs in the posterior region's callosal and subcortical regions of interest. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. CONCLUSIONS: WM changes in early AD are concentrated in posterior cerebral areas, with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual's deficits in early AD.","Aged;Aged, 80 and over;Aging;Alzheimer Disease/ pathology;Brain/ pathology/ultrastructure;Case-Control Studies;Cognition Disorders/ diagnosis;Female;Humans;Image Processing, Computer-Assisted;Logistic Models;Magnetic Resonance Imaging;Male;Neuropsychological Tests","Kavcic, V.;Ni, H.;Zhu, T.;Zhong, J.;Duffy, C. J.",2008,Nov,10.1016/j.jalz.2008.07.001,0,
3446,Association between neuropathology and brain volume in the Framingham Heart Study,"Studies of clinical and community cohorts have shown that antemortem imaging measures of hippocampal volume have correlated with postmortem Alzheimer pathology. Fewer studies have examined the relationship between both Alzheimer and cerebrovascular pathology, and antemortem brain imaging. The aim of this study was to correlate antemortem brain magnetic resonance imaging (MRI) volumes with postmortem brain pathology (both Alzheimer-related and cerebrovascular) in a community-derived cohort from the Framingham Heart Study. Participants (n=59) from the Framingham Heart Study were included if they were enrolled in the brain autopsy program and underwent antemortem clinical evaluation, neuropsychological testing, and brain MRI. Cortical neurofibrillary tangle pathology correlated with lower total cerebral brain (beta+/-SE=-0.04+/-0.01, P=0.004) and hippocampal volumes (beta+/-SE=-0.03+/-0.02, P=0.044) and larger temporal horns (log-transformed, beta+/-SE=0.05+/-0.01, P=0.001). Similar findings were seen between total/cortical neuritic plaques and total cerebral brain and temporal horn volume. White matter hyperintensities (also log-transformed) were best predicted by the presence of deep nuclei microinfarcts (beta+/-SE=0.53+/-0.21, P=0.016), whereas hippocampal volume was significantly decreased in the presence of hippocampal sclerosis (beta+/-SE=-1.23+/-0.30, P<0.001). This study showed that volumetric MRI measures correlated with postmortem Alzheimer-related and cerebrovascular neuropathology in this community-derived cohort, confirming that these MRI measures are important antemortem surrogates for these dementia-related pathologies.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Autopsy;Brain/ pathology;Cerebrovascular Disorders/ pathology;Female;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size","Kaur, B.;Himali, J. J.;Seshadri, S.;Beiser, A. S.;Au, R.;McKee, A. C.;Auerbach, S.;Wolf, P. A.;DeCarli, C. S.",2014,Jul-Sep,10.1097/wad.0000000000000032,0,
3447,Late postpartum preeclampsia with posterior reversible encephalopathy syndrome,"Posterior reversible encephalopathy syndrome is a reversible syndrome characterized by headache, seizures, altered mentation, and loss of vision associated with white matter changes on imaging. We report here a 27 year-old lady three weeks postpartum, presenting with posterior reversible encephalopathy syndrome. She was treated successfully with antihypertensives and showed dramatic improvement. This condition is important to recognize and needs to be treated promptly to prevent morbidity and mortality in pregnancy and postpartum.",,"Kauntia, R.;Valsalan, R.;Seshadri, S.;Pandit, V.;Prabhu, M.",2009,1,,0,
3448,Dementia following strokes in the mesencephalon and diencephalon,"Six patients had ischemic infarcts in the paramedian thalamic, subthalamic, and mesencephalic areas. In addition to ocular motility problems, ataxia, dysmetria, and mild pyramidal signs, there were consistent behavioral observations and neuropsychological findings. All of the patients had initial deficits in arousal, and gradually improved to normal wakefulness. When awake, all of the patients had impaired attention, mental control, and slowed verbal and motor responsiveness. They were apathetic, poorly motivated, and affect was flat or occasionally labile. All of the patients had a memory disorder characterized by anterograde and retrograde loss. One patient had significant language impairment. These deficits persisted in all but one patient who had a predominantly mesencephalic lesion. We believe the cluster of findings in these patients constitutes a characteristic syndrome of dementia related to paramedian mesencephalic and diencephalic infarcts. This syndrome bears close resemblance to that associated with some subcortical degenerative disorders such as progressive supranuclear palsy. In cases of paramedian mesencephalic and diencephalic infarcts, however, computed tomography and magnetic resonance imaging can delineate clinicoanatomic relationships that account for specific constituents of the syndrome.","Adult;Aged;Amnesia/etiology;Attention/physiology;Cerebral Infarction/ complications/psychology/radiography;Cognition Disorders/etiology;Dementia/ etiology/psychology;Diencephalon/radiography;Female;Humans;Male;Mesencephalon/radiography;Middle Aged;Neuropsychological Tests;Tomography, X-Ray Computed","Katz, D. I.;Alexander, M. P.;Mandell, A. M.",1987,Nov,,0,
3449,Proton magnetic resonance spectroscopy of vascular- and Alzheimer-type dementia,Objective: To identify biochemical differences in brain tissue between patients with dementia of the Alzheimer type and vascular dementia. Design and Subjects: Proton magnetic resonance spectroscopy was used to compare 10 patients with dementia of the Alzheimer type and 8 age-matched patients with vascular dementia. Results: The ratios of N-acetyl groups to creatine and N- acetyl groups to choline were lower in regions of subcortical white matter in patients with vascular dementia than in patients with dementia of the Alzheimer type (P<.02). Conclusion: Proton magnetic resonance spectroscopy may be useful in distinguishing between dementia of the Alzheimer type and vascular dementia.,adult;aged;Alzheimer disease;article;clinical article;clinical protocol;controlled study;dementia;diagnostic imaging;differential diagnosis;female;human;male;multiinfarct dementia;neurologic disease;priority journal;proton nuclear magnetic resonance;white matter,"Kattapong, V. J.;Brooks, W. M.;Wesley, M. H.;Kodituwakku, P. W.;Rosenberg, G. A.",1996,,,0,
3450,A case of MM1+2 Creutzfeldt-Jakob disease with a longitudinal study of EEG and MRI,"We report a case of definite MM1 + 2 sporadic Creutzfeldt-Jakob disease (sCJD). A 66-year-old woman was admitted to our hospital with memory disturbance and disorientation for three months. On admission she presented a progressive cognitive insufficiency. Electroencephalography (EEG) revealed a frontal intermittent rhythmical delta activity (FIRDA) and the brain magnetic resonance imaging (MRI) showed high signal intensities in cerebral cortex on diffusion weighted images (DWI). After four months from the onset, she reached the akinetic mutism state followed by myoclonus. Follow up examination revealed that periodic synchronous discharge (PSD) was found in EEG, and DWI revealed enlargement of high signal intensity lesions in cerebral cortex. At seven months from the onset, PSD and high signal intensities of cortex became unclear with disappearance of myoclonus, and brain white matter lesions were evident on MRI. Serial studies of EEG and MRI revealed that PSD generalized from frontal lobe dominant pattern, while high signal intensity lesions of cortex diffusely increased on DWI. At ten months from the onset patient died. Pathological examination in brain showed moderate and diffuse neuronal cell loss and gliosis in cerebral cortex corresponding with DWI changes. The genotype at codon 129 of the prion protein (PrP) was homozygous methionine (MM) and the type of protease-resistant PrP (PrPres) was the mixed type of 1 and 2 in Western blot analysis. It has been rare to analyze the changes of EEG and MRI in the entire stage and to investigate pathological finding in the case of sCJD-MM1 + 2. A longitudinal examination of EEG and MRI is useful for early diagnosis of CJD. Also we could correlate these findings with clinical and histopathological phenotype.",,"Katsube, M.;Shiota, Y.;Harada, T.;Shibata, H.;Nagai, A.",2013,Nov,,0,
3451,Involvement of the frontotemporal lobe and limbic system in amyotrophic lateral sclerosis: As assessed by serial computed tomography and magnetic resonance imaging,"The present paper concerns serial examinations of computed tomography (CT) and magnetic resonance imaging (MRI) in 22 patients with sporadic amyotrophic lateral sclerosis (ALS). Supranuclear ophthalmoplegia developed in 13 and dementia in 3 patients. The investigations showed gradually progressive atrophy, first in the frontal and anterior temporal lobes then in the precentral gyrus, and later in the postcentral gyrus, anterior part of the cingulate gyrus, corpus callosum and brain stem tegmentum. MRI revealed high intensity signals on T2-weighted images in the precentral and adjacent gyri, frontotemporal white matter and pyramidal tract as well as rarely in the globus pallidus and thalamus. These neuroradiological changes were not related to the duration of the clinical course or to the degree of the motor impairment. These alterations may play a critical role in the supranuclear ophthalmoplegia seen in ALS patients. The dementia of ALS probably reflects involvement of both the frontotemporal lobes and limbic system.",,"Kato, S.;Hayahi, H.;Yagishita, A.",1993,1993,,0,
3452,Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using (99m)Tc-HMPAO SPECT,"Background: Subcortical ischemic vascular dementia (SVD) caused by small-artery disease is a major cause of dementia. It still remains unclear, however, whether SVD may present with localized regional cerebral blood flow (rCBF) changes. We aimed to clarify the local rCBF changes associated with dementia in patients with early-stage SVD. Methods: The subjects consisted of 15 patients with early-stage SVD [Mini Mental State Examination (MMSE) score: 20 ± 3.5] without apparent brain atrophy (SVD group), 11 patients without dementia with white matter lesions (non-dementia-WML group) and 16 age-matched controls. All the subjects were right-handed and underwent brain perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging and cognitive function testing. Statistical analysis of the differences in the SPECT rCBF was performed by SPM2. The degree of severity of the WMLs was evaluated based on the Scheltens rating scale. Results: The results of SPM analysis revealed that the rCBF in the SVD group was significantly decreased in the pulvinar nuclei of the thalamus of both sides as compared with that in the controls, and in the left pulvinar nucleus as compared with that in the non-dementia-WML group. On the other hand, SPM analysis revealed no significant reduction in rCBF in the non-dementia-WML group as compared with that in the controls. The WMLs in the left parietal region were severer in the SVD group than in the non-dementia-WML group. Conclusions: In patients with early-stage SVD without apparent brain atrophy, significant rCBF reduction in the bilateral pulvinar nuclei as compared with that in normal controls, and in the left pulvinar nucleus as compared with that in patients without dementia with WMLs was found. Copyright © 2008 S. Karger AG.",,"Kato, H.;Yoshikawa, T.;Oku, N.;Imaizumi, M.;Takasawa, M.;Kimura, Y.;Kajimoto, K.;Tanaka, M.;Kitagawa, K.;Hori, M.;Hatazawa, J.",2008,November,,0,
3453,White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study,"White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction.","Aged;Aged, 80 and over;Dementia, Multi-Infarct/*physiopathology/radiography;Evoked Potentials, Somatosensory;Female;Humans;Male;Middle Aged;Neural Conduction;*Tomography, X-Ray Computed","Kato, H.;Sugawara, Y.;Ito, H.;Kogure, K.",1990,Feb,,0,
3454,Sporadic cerebral amyloid angiopathy with ischemic leukoencephalopathy and microbleeds. Cause for a rapidly progressive dementia syndrome,We describe a 72-year-old patient with rapidly progressive dementia and a complex focal seizure. Magnetic resonance (MR) imaging revealed leukoencephalopathy with the involvement of the U-fibers as well as cortical and subcortical microbleeds. Brain biopsy confirmed the diagnosis of cerebral Aβ amyloid angiopathy (CAA). The presented case illustrates the significance of CAA as a cause of rapidly progressive dementia and leukoencephalopathy and points out the importance of T2-weighted MR imaging in the evaluation of dementia. © Springer Medizin Verlag 2005.,,"Katchanov, J.;Bohner, G.;Könneker, M.;Kopp, U.;Izadpanah, K.;Larmann, E.;Klingebiel, R.;Van Landeghem, F.;Masuhr, F.;Zschenderlein, R.",2005,October,,0,
3455,Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis: The first report of a CLN8 mutation in Japan,"Neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically heterogeneous neurodegenerative lysosomal diseases. Fourteen distinct NCL subtypes (CLN1-CLN14) are known, and they are caused by mutations in different genes. CLN8 was first identified in Finnish patients, and the phenotype was subsequently found in Turkish, Italian, and Pakistani patients. We report a 6-year-old Japanese boy with NCL with a novel missense mutation in CLN8. At the age of 3 years, he manifested frequent drop seizures, and then progressively developed motor difficulties with an ataxic gait, myoclonus, left conjugate deviation, and rotational nystagmus. At age 5, he developed profound visual difficulty and dysphagia, and he has now lost his mobility. A bone marrow examination at age 5 showed sea-blue histiocytes. An electroretinogram was non-recordable. No giant somatosensory evoked potentials were found. Brain magnetic resonance imaging revealed bilateral diffuse hyperintensities in the white matter around the lateral ventricles and cerebellar and pontine atrophy on T2-weighted images. In a lysosomal enzyme study, the palmitoyl-protein-thioesterase and pepinase activity was within normal limits. Whole-exome sequencing revealed a homozygous CLN8 mutation: c.620T>G (p.L207R). His parents were both heterozygous for this mutation. To our knowledge, this is the first report of a CLN8 mutation in late infantile NCL in Japan.",,"Katata, Y.;Uematsu, M.;Sato, H.;Suzuki, S.;Nakayama, T.;Kubota, Y.;Kobayashi, T.;Hino-Fukuyo, N.;Saitsu, H.;Kure, S.",2016,1,,0,
3456,Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice,"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T2-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11-17months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.","Alzheimer Disease/ genetics;Amyloid beta-Peptides/metabolism;Animals;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Disease Models, Animal;Mice;Mice, Inbred C57BL;Mice, Transgenic;Mutation;Nerve Fibers, Myelinated/pathology;Neurofibrillary Tangles/ pathology;Plaque, Amyloid/ pathology;Time Factors","Kastyak-Ibrahim, M. Z.;Di Curzio, D. L.;Buist, R.;Herrera, S. L.;Albensi, B. C.;Del Bigio, M. R.;Martin, M.",2013,Nov,10.1016/j.mri.2013.06.013,0,
3457,"Global brain atrophy and corticospinal tract alterations in ALS, as investigated by voxel-based morphometry of 3-D MRI","In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58±9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59±11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p=0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p < 0.01 in the right-hemispheric primary motor cortex (area of the highest Z-score) and in the left medial frontal gyrus. Furthermore, regional white matter alterations were observed along the corticospinal tracts bilaterally and in multiple smaller areas including corpus callosum, cerebellum, frontal and occipital subcortical regions. Besides considerable global atrophy in ALS, the topography of ALS-associated cerebral morphological changes could be mapped using VBM, in particular white matte signal changes along the bilateral corticospinal tracts, but also in extra-motor areas. VBM might be a potential tool to visualize disease progression in future longitudinal studies. © 2005 Taylor & Francis.",,"Kassubek, J.;Unrath, A.;Huppertz, H. J.;Lulé, D.;Ethofer, T.;Sperfeld, A. D.;Ludolph, A. C.",2005,December,,0,
3458,The cerebro-morphological fingerprint of a progeroid syndrome: White matter changes correlate with neurological symptoms in xeroderma pigmentosum,"Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid syndrome. It has recently been shown that the underlying DNA repair defect plays a central role in the aging process. In addition to skin symptoms, various premature neurological abnormalities have been reported. Methodology/Principal Findings: We present the clinical neurological phenotype in 14 XP patients (seven subtypes), in seven of these patients together with conventional and multiparametric advanced MRI data to assess the macrostructural and microstructural cerebral morphology in comparison to controls, including volumetric measurements, MR spectroscopy ((1)H MRS), and diffusion tensor imaging (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and mild cognitive deficits. DTI demonstrated significantly reduced WM directionality in all regions investigated, i.e. the thalamus, the corticospinal tracts and the dorsal corpus callosum. Single patients showed a marked relative hippocampal volume reduction, but the patients were not different from controls in the volumetric measurements of hippocampal and whole brain volumes at group level. However, (1)H MRS demonstrated that the hippocampal formation was metabolically altered. Conclusions: The most prominent feature was the white matter affectation, as assessed by DTI, with volume and directionality reductions of the fiber projections involving both the craniocaudal fibers and the interhemispheric connections. These findings, although heterogeneous among the study sample, could be correlated with the clinico-neurological symptoms. The imaging findings support the position that myelin structures degrade prematurely in the brain of XP patients. © 2012 Kassubek et al.",,"Kassubek, J.;Sperfeld, A. D.;Pinkhardt, E. H.;Unrath, A.;Müller, H. P.;Scharffetter-Kochanek, K.;Ludolph, A. C.;Berneburg, M.",2012,,,0,
3459,Microstructural white matter changes underlying cognitive and behavioural impairment in ALS - An in vivo study using DTI,"Background: A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. Methods: We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Results: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. Conclusion: In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.",adult;aged;amyotrophic lateral sclerosis;article;behavior change;cognitive defect;cohort analysis;controlled study;corpus callosum;diffusion tensor imaging;disease association;executive function;female;frontal lobe;human;in vivo study;major clinical study;male;memory;mental performance;neuropsychological test;nuclear magnetic resonance scanner;prefrontal cortex;pyramidal tract;temporal cortex;white matter;MAGNETOM Verio,"Kasper, E.;Schuster, C.;Machts, J.;Kaufmann, J.;Bittner, D.;Vielhaber, S.;Benecke, R.;Teipel, S.;Prudlo, J.",2014,,,0,3460
3460,Microstructural white matter changes underlying cognitive and behavioural impairment in ALS--an in vivo study using DTI,"BACKGROUND: A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. METHODS: We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. RESULTS: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. CONCLUSION: In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients.","Adult;Aged;Aged, 80 and over;Amyotrophic Lateral Sclerosis/ pathology/ physiopathology;Behavior/ physiology;Cognition;Cohort Studies;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Neuropsychological Tests;White Matter/ pathology/physiopathology","Kasper, E.;Schuster, C.;Machts, J.;Kaufmann, J.;Bittner, D.;Vielhaber, S.;Benecke, R.;Teipel, S.;Prudlo, J.",2014,,10.1371/journal.pone.0114543,0,
3461,"Psychoses in patients with Parkinson's disease; their frequency, phenomenology, and clinical correlates","The frequency, phenomenology, and risk factors of hallucinations and delusions were investigated in 64 consecutive inpatients with Parkinson's disease. Fifty patients were admitted to our hospital with symptoms related to Parkinson's disease: psychiatric problems 27 (psychosis 22; anxiety 2; depression 2; mania 1): motor symptoms, 20 (wearing-off 5; akinesia 4; freezing 4; postural instability 4; dyskinesia 2; tremor 2; dystonia 1), and sensory symptoms, 3. Fourteen patients were admitted with other medical problems (pneumonia 4; cerebral infarction 3; bone fracture 3; lumbago 2; seizure 1; cat bite 1). Totally 49 patients had psychiatric problems. Psychosis was present in 43 patients, dementia in 10, depression in 8, mania in 1, anxiety in 10, agitation in 6, stereotypy in 2, and hypersexuality in 2. Of the 43 patients with psychoses, 40 presented with visual hallucinations, 18 with auditory hallucinations, and 23 with delusions. To determine what the clinical correlates with the severity of psychosis were, we divided the patients into 3 groups: the severe group, 22 patients admitted because of psychotic symptoms; the mild group, 21 patients admitted because of problems other than psychosis but presenting psychotic symptoms; and the control group, 21 patients who had no psychotic symptoms. Incidences of auditory hallucinations and delusions were higher in the severe group as compared to the mild group. Patients in the severe group had higher Hoehn-Yahr stages, lower Mini-Mental State Examination scores, decreased H/M ratios of cardiac 123I-MIBG uptake, and lower frequencies of background activity on electroencephalograms. There were no differences in age at admission, age at onset of Parkinson's disease, duration of illness, amounts of levodopa and dopamine agonists received, Hamilton's depression rating scores, and brain MR findings, including atrophy and ischemic changes. Emergence of psychotic symptoms in parkinsonian patients appears to be clearly associated with impaired cognitive function. Therefore, it may be associated with the disease process itself. Terms such as dopaminomimetic or levodopa-induced psychosis may not be appropriate when describing psychosis in Parkinson's disease.",(3 iodobenzyl)guanidine i 123;dopamine receptor stimulating agent;levodopa;agitation;akinesia;anxiety disorder;article;auditory hallucination;bite;brain atrophy;brain infarction;brain ischemia;clinical article;cognition;controlled study;correlation analysis;delusion;dementia;depression;disease association;disease duration;disease severity;dopaminergic activity;dyskinesia;dystonia;electroencephalogram;fracture;hallucination;Hamilton Depression Rating Scale;hospital admission;human;low back pain;mania;Mini Mental State Examination;motor dysfunction;neuropathology;nuclear magnetic resonance imaging;Parkinson disease;phenomenology;pneumonia;psychosis;risk factor;seizure;sensory dysfunction;sexual dysfunction;stereotypy;tremor;visual hallucination,"Kashihara, K.;Ohno, M.;Katsu, Y.",2005,,,0,
3462,Prevalence of silent stroke in patients presenting with initial stroke: the Framingham Study,"It is common to find computed tomography scan evidence of prior stroke without a history of such an event. The frequency, risk factors for, and relevance of silent strokes are unknown. The Framingham cohort of 5,184 men and women aged 30-62 years and free of stroke at entry to the study have been followed with periodic examinations since 1950. We studied the silent strokes found on computed tomography scan of all initial strokes that occurred between January 1, 1979, and July 31, 1987. During these 8 1/2 years, 164 initial strokes occurred; 124 had computed tomography scans performed. There were 13 (10%) with silent stroke, 71 had abnormalities related to their presenting acute stroke, and 40 had normal computed tomography scans. There were 15 silent lesions; eight were lacunar infarcts in the basal ganglia-internal capsule area, seven were small cortical infarcts. Glucose intolerance was the sole risk factor that occurred significantly more frequently (11 of 13) in the group with silent lesions (p less than 0.04) than in the group with computed tomography evidence of acute stroke. Silent stroke is not rare; it was present in at least 10% of acute initial stroke patients arising in a general population. The relation of these silent lesions to the development of ""vascular"" dementia and poststroke disability deserves further study.","Cerebral Infarction/radiography;Cerebrovascular Disorders/physiopathology/*radiography;Female;Glucose Tolerance Test;Humans;Male;Medical Records;Risk Factors;*Tomography, X-Ray Computed","Kase, C. S.;Wolf, P. A.;Chodosh, E. H.;Zacker, H. B.;Kelly-Hayes, M.;Kannel, W. B.;D'Agostino, R. B.;Scampini, L.",1989,Jul,,0,
3463,Magnetic resonance imaging study of the brain in aged volunteers: T2 high intensity lesions and higher order cortical function,"The aims of the present study were to clarify the findings of magnetic resonance imaging (MRI) in the aging brain, and to relate the MPd findings to higher order cortical function. A total of 118 healthy aged volunteers (41 men, 77 women) underwent cranial MRI electroencephalography (EEG), Benton visual retention test (BVRT) and interview. The subjects had no past history or clinical evidence of cerebrovascular disorder, head trauma or dementia and were living at home without any difficulty. The majority of the subjects have participated in this series of studies since 1982. Using a 1.5 T superconductive MR instrument, T1-weighted, proton density and T2-weighted images were obtained. The MRI data were rated visually by regarding 12 items according to fixed criteria. T2 high signal intensity (T2HSI) lesions were found in 69.5% of subjects, the prevalence of which increased with age. T2HSI lesions were most frequently found in the basal ganglia (61.9%), followed by the thalamus (39.0%), parietal lobe (37.0%), temporal lobe (12.7%) and pons (8.5%). Among these lesions, lacunar infarction showed low signal intensity in T1-weighted images and was found in 24.6% of subjects, the prevalence also increasing with age. These findings, including brain atrophy determined according to similar criteria, were correlated closely with the subjects' age. The results of BVRT showed a close relation with T2HSI, suggesting that T2HSI may influence cognitive function. When the subjects were classified according to the presence of T2HSI, lacunar infarction and EEG abnormalities, brain atrophy was significantly milder in a group of subjects with T2HSI(-), lacunar infarction(-) and normal EEG than in the other groups. This suggests that changes seemingly representing physiological aging may be promoted by another pathological which also exerts influences on higher order cerebral function.",,"Kasahara, H.;Yamada, H.;Tanno, M.;Kobayashi, M.;Karasawa, A.;Endo, K.;Ushijima, S.",1995,1995,,0,
3464,MRI study of the brain in aged volunteers: T2 high signal intensity lesions and high cortical function,"In order to characterize age-related and chronological changes of the brain, longitudinal studies of aged volunteers were conducted using computed tomography since 1982. The present paper discusses correlations between brain function and findings of MR images which were obtained a using 1.5 T superconductive MR instrument since 1989. A total of 118 volunteers aged 60 to 88 years old with a mean age of 75.0 +/- 6.7 participated in the study, which consisted of MRI, EEG recording, the Benton Visual Retention Test and a medical interview. Subjects with a past history or clinical evidence of CVD, head trauma or dementia were excluded from the study. Incidence of T2 high signal intensity lesions increased with age. Some showing T1 low signal intensity in the same lesion were considered to be lacunar infarction, over all incidence of which was 24.6%. Numbers of correct responses on the BVRT showed a negative correlation with numbers of T2 high signal intensity lesions. Although the aged volunteers in the present study could achieve all activity of daily living without any trouble, high cortical function evaluated by visuoperceptual performance of BVRT was somewhat disturbed in participants with multiple T2 high signal intensity lesions. Brain atrophy seems to be more advanced in groups with T2 hyper intensity lesions than in the group without them. These findings may support the notion that T2 high signal intensity lesions are not merely an index of ageing but pathologic lesions accompanied with senescence, although further studies including clinicopathological correlation are necessary to establish this concept.","Aged;Aged, 80 and over;Aging/ pathology;Brain/ pathology;Cerebral Cortex/pathology/ physiology;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retention (Psychology)","Kasahara, H.;Tanno, M.;Yamada, H.;Endoh, K.;Kobayashi, M.;Karasawa, A.",1993,Oct,,0,
3465,De novo mutations in hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS),"Objective: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is caused by autosomal-dominantly inherited mutations in the colony stimulating factor 1 receptor (CSF1R) gene, and is clinically characterized by a progressive cognitive and motor decline leading to death within several years. Methods: In a continuous series of 25 patients with adult-onset leukoencephalopathy of unknown cause, we genetically confirmed HDLS in 6 families. Affected and nonaffected individuals were examined clinically and by brain MRI studies. Results: HDLS presented as prominent dementia and apraxia, often with extrapyramidal and pyramidal signs, rarely with ataxia. White matter MRI changes were detectable early in the disease course. Family history was negative in 4 of 6 index patients. In 2 of 6 index patients, we could confirm the occurrence of de novo mutations in the CSF1R gene. One family showed possible incomplete penetrance: the 69-year-old father of the index patient carried a CSF1R mutation but was clinically unaffected. In one family, the parents were apparently unaffected and not available for genetic testing. Conclusions: Typical clinical phenotype and early brain MRI alterations can help to guide the diagnosis of HDLS. Because we confirmed de novo mutations in one-third of patients with CSF1R mutations, this diagnosis should be considered even in the absence of a family history. Furthermore, we present evidence for reduced penetrance of a CSF1R mutation. These results have substantial impact for genetic counseling of asymptomatic individuals at risk and should foster research into disease-modifying factors. © 2013 American Academy of Neurology.",colony stimulating factor 1 receptor;colony stimulating factor receptor;unclassified drug;adult;aged;apraxia;article;ataxia;autosomal dominant disorder;clinical article;clinical assessment;degenerative disease;dementia;disease course;extrapyramidal symptom;family assessment;family history;father;female;gene mutation;genetic screening;hereditary diffuse leukoencephalopathy with axonal spheroid;heterozygote;human;leukoencephalopathy;male;middle aged;neuroimaging;nuclear magnetic resonance imaging;parent;penetrance;priority journal;pyramidal sign;tumor spheroid;white matter lesion,"Karle, K. N.;Biskup, S.;Schüle, R.;Schweitzer, K. J.;Krüger, R.;Bauer, P.;Bender, B.;Nägele, T.;Schöls, L.",2013,,,0,
3466,A case of multiple cavernous angioma with dementia,"We reported a 65-year-old man who developed dementia since 50 years of age. His consciousness was clear but he was indifferent to his illness. Also, the luck of attention was recognized when we underwent examinations and the result of intellectual test varied every time we performed. His memory function was almost normal on the examination which was performed when he was cooperative. Magnetic resonance imaging (MRI) disclosed multiple tiny lesions (more than 130 in all) in cerebrum, brainstem, cerebellum and spinal cord. These lesions were compatible with multiple cavernous angioma. Most of lesions manifested high-density area on cranial CT. Though the multiplicity of foci indicated the possibility of familial occurrence, he was considered to be a sporadic case on his lineage investigation and the brain MRI of his only son. In this case, neither headache nor seizures which were known as the major clinical features of intracerebral cavernous angioma was observed. He was diagnosed as having white matter dementia characterized by attentional dysfunction, decrement of volition and less memory disturbance. We speculated that he developed symptomatic dementia by the sum of multiple minor degeneration, especially in frontal lobe white matter, caused by repeated minor bleeding from cavernous angiomas.",,"Kariya, S.;Kawahara, M.;Suzumura, A.",2000,2000,,0,
3467,Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension,"Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (> or = 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patients' neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.",Aged;Basal Ganglia/ metabolism;Cerebral Infarction/complications/diagnosis/ genetics;Cerebrovascular Circulation/genetics;Female;Heterozygote;Humans;Hypertension/complications/ genetics;Magnetic Resonance Imaging;Male;Middle Aged;Pedigree;Protein C Deficiency/complications/ genetics,"Kario, K.;Sakata, T.;Higashikawa, M.;Katayama, Y.;Hoshide, S.;Shimada, K.;Miyata, T.",2001,Aug,,0,
3468,Effect of thrombin inhibition in vascular dementia and silent cerebrovascular disease: An MR spectroscopy study,"Background and Purpose - Silent cerebrovascular disease (CYD) has been proposed as a predisposing condition for clinically overt stroke and vascular dementia. Recently, we found increased thrombin generation in silent CVD patients. Here, we report the effect of thrombin inhibition using a potent selective thrombin inhibitor on the cerebral metabolism and function in peripheral arterial occlusive disease (PAOD) patients with or without silent CVD. Methods - We examined 17 mild chronic PAOD patients, including 2 cases of vascular dementia. We divided the patients into 2 groups: 1 was the advanced CVD group with multiple lacunar infarction and/or advanced periventricular hyperintensity detected by brain MRI (n=12), and the other was the no CVD group that had none of these abnormalities (n=5). We assessed the cerebral biochemical compounds in the deep white matter area and cerebellar hemisphere (8 cm3) by proton MR spectroscopy before and after infusion of argatroban (10 mg/d IV) over 2 hours for 7 days. Results - The ratio of N-acetylasparate (NAA) to total creatine (Cre) in the deep white matter area was significantly lower in the advanced CVD group than in the no CVD group, whereas there were no significant differences in this ratio in the cerebellar hemisphere between the 2 groups. In the former group, this decreased NAA/Cre ratio significantly increased after argatroban therapy, whereas there was no change in the latter group. The 2 patients with vascular dementia showed clinical improvement with marked increases in the NAA/Cre ratio and mini-mental score. Conclusions - These results suggest that increased thrombin generation may have some pathophysiological roles in developing vascular dementia and its chronic predisposing conditions. Thrombin inhibition may break this vicious cycle and lead to clinical improvement.",argatroban;creatine;n acetylaspartic acid;thrombin inhibitor;adult;aged;article;blood clotting;brain metabolism;cerebrovascular disease;controlled study;disease association;drug effect;female;human;intravenous drug administration;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance spectroscopy;pathophysiology;peripheral occlusive artery disease;priority journal;treatment outcome;white matter,"Kario, K.;Matsuo, T.;Hoshide, S.;Umeda, Y.;Shimada, K.",1999,,,0,
3469,Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts,"Megalencephalic leukoencephalopathy with subcortical cysts (MLC) (MIM #. 604004) is a rare autosomal recessive neurological disorder characterized by macrocephaly, motor and cognitive decline, ataxia, spasticity and occasional seizures. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen white matter of the cerebral hemispheres and subcortical cysts in the anterior temporal and frontoparietal region. Mutations in MLC1(22q13.33) and GLIALCAM have been identified in patients with MLC. Mutations in MLC1 account for approximately 75% of the cases.MLC was suspected in eighteen Iranian patients from sixteen families based on positive clinical findings including macrocephaly beginning in the first year, neurocognitive deterioration, seizure or loss of consciousness after minor head trauma. All except two were born to consanguineous parents. Brain MRI images were compatible with MLC and confirmed the diagnosis. Sequencing of entire coding region of MLC1 was performed for seventeen patients and mutations in MLC1 were detected in all of them. Eight novel mutations and seven previously reported mutations were identified. This report shows that MLC is relatively common in Iranian population, as expected for rare diseases with high inbreeding, with a surprisingly high frequency of novel mutations.",,"Kariminejad, A.;Rajaee, A.;Ashrafi, M. R.;Alizadeh, H.;Tonekaboni, S. H.;Malamiri, R. A.;Ghofrani, M.;Karimzadeh, P.;Mohammadi, M. M.;Baghalshooshtari, A.;Bozorgmehr, B.;Kariminejad, M. H.;Postma, N.;Abbink, T. E. M.;van der Knaap, M. S.",2015,1,,0,
3470,Neuroradiological and postmortem findings of intravascular lymphomatosis: A case report,"The authors report the case of 61 year old man with intravascular lymphomatosis (neoplastic angioendotheliomatosis). The patient presented progressive dementia and left hemiparesis. Magnetic resonance imaging (MRI) showed multiple small infarctions in the corpus callosum and cerebral white matter. Four months after presenting the initial symptoms, he died of respiratory failure. Postmortem findings revealed a multiple intravascular proliferation of a typical mononuclear cells in the brain, the lungs, the adrenals, and in the other organs. The immunohistochemical findings revealed that the malignant cells were of B lymphoid origin. In review of the literature and including this case, only seven cases have reported on the MRI findings of this disease. Based on our findings, we fell that when marking a differential diagnosis of rapidly progressive dementia and a multifocal vascular disease, intravascular lymphomatosis should considered among the possible causes.",,"Karasawa, H.;Matsumoto, H.;Naito, H.;Sugiyama, K.;Ueno, J.;Kin, H.;Okeda, R.",1996,1996,,0,
3471,Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study,"BACKGROUND: Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. OBJECTIVE: We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function. METHODS: Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). RESULTS: In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (beta= -0.03 to -0.05+/-0.02) and the Hooper Visual Organization Test (beta= -0.09 to -0.12+/-0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (beta= -0.01+/-0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. CONCLUSIONS: In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.",,"Karakis, I.;Pase, M. P.;Beiser, A.;Booth, S. L.;Jacques, P. F.;Rogers, G.;DeCarli, C.;Vasan, R. S.;Wang, T. J.;Himali, J. J.;Annweiler, C.;Seshadri, S.",2016,Feb 6,10.3233/jad-150991,0,
3472,In Vivo Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer's Disease,"The corpus callosum is the largest commissural fiber connecting left and right hemisphere of the brain. Emerging evidence suggests that a variety of abnormalities detected in the microstructure of this white matter fiber can be an early event in Alzheimer's disease (AD) pathology. However, little is known about tissue characteristics of these abnormalities and how these abnormalities evolve during AD progression. In this study, we measured in vivo magnetic resonance transverse relaxation times (T2) to longitudinally monitor changes in tissue integrity and abnormalities related to myelination and demyelination processes in corpus callosum of AD mouse models. The most striking finding of our study was a significant elongation of T2 values in the corpus callosum at 10, 14, 16 and 18 months of age compared to age-matched wild-type mice. In contrast, the gray matter regions surrounding the corpus callosum, such as the cortex and hippocampus, showed a significant T2 decrease compared to wild-type mice. Histological analyses clearly revealed demyelination, gliosis and amyloid-plaque deposition in the corpus callosum. Our results suggest that demyelinating and inflammatory pathology may result in prolonged relaxation time during AD progression. To our knowledge, this is the first in vivo T2 study assessing the microstructural changes with age in the corpus callosum of the Tg2576 mouse model and it demonstrates the application of T2 measurement to noninvasively detect tissue integrity of the corpus callosum, which can be an early event in disease progression.","Alzheimer Disease/*pathology/physiopathology;Amyloid beta-Protein Precursor/genetics/metabolism;Animals;Astrocytes/pathology;Cerebral Cortex/pathology/physiopathology;Corpus Callosum/*pathology/physiopathology;Demyelinating Diseases/pathology/physiopathology;Disease Models, Animal;Disease Progression;Female;Fluorescent Antibody Technique;Hippocampus/pathology/physiopathology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mice, Inbred C57BL;Mice, Transgenic;Thalamus/pathology/physiopathology","Kara, F.;Hofling, C.;Rossner, S.;Schliebs, R.;Van der Linden, A.;Groot, H. J.;Alia, A.",2015,,,0,
3473,Updated standardized endpoint definitions for transcatheter aortic valve implantation: The valve academic research consortium-2 consensus document (varc-2),"Objectives: The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection. BACKGROUND: A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous. METHODS AND Results: Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints. Conclusions: This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair). Published on behalf of the European Association for Cardio-Thoracic Surgery. The article has been co-published in the European Heart Journal, EuroIntervention, Journal of the American College of Cardiology, and Journal of Thoracic and Cardiovascular Surgery. All rights reserved. © The Author 2012.",,"Kappetein, A. P.;Head, S. J.;Généreux, P.;Piazza, N.;Van Mieghem, N. M.;Blackstone, E. H.;Brott, T. G.;Cohen, D. J.;Cutlip, D. E.;Van Es, G. A.;Hahn, R. T.;Kirtane, A. J.;Krucoff, M. W.;Kodali, S.;Mack, M. J.;Mehran, R.;Rodés-Cabau, J.;Vranckx, P.;Webb, J. G.;Windecker, S.;Serruys, P. W.;Leon, M. B.",2012,,,0,
3474,Treatment of small deep infarcts of the brain,,acetylsalicylic acid;artery occlusion;brain infarction;brain stem infarction;computer assisted tomography;diabetes mellitus;dysarthria;hemiparesis;hemiplegia;human;hypertension;motor dysfunction;multiinfarct dementia;nuclear magnetic resonance imaging;prognosis;risk factor;short survey;cerebrovascular accident,"Kappelle, L. J.;Adams Jr, H. P.",1994,,,0,
3475,Demographic and biological influences on cognitive reserve,"High levels of education have been linked to reduced risk of dementia, whereas magnetic resonance imaging (MRI) white matter hyperintensities (WMH) have been shown to correspond to deficits in executive functioning and psychomotor speed. We studied education, WMH, age, and gender as predictors of better cognitive performance, or cognitive reserve, in the normal elderly. The Repeatable Battery for the Assessment of Neuropsychological Status, supplemented by the Trail Making Test, the Stroop Test, and the California Computerized Assessment Package, were administered to 95 volunteers, aged 75-90 years. Quantitative MRI was used to determine the extent and location of WMH. Using factor analysis, the cognitive measures were reduced to three factors: verbal memory, information-processing speed/executive functioning, and visuospatial skills. When entered into a hierarchical regression, age and gender were the primary predictors of verbal memory, accounting for 34.8% of the variance, with education and WMH adding only 9%. WMH, education, and age contributed independently to predicting speed of information processing/executive functioning, explaining 22.5% of the variance. Only education and age were predictors of visuospatial skills, explaining 14.8% of the variance. These data suggest that cognitive reserve represents a combination of factors that independently determine the threshold for competence within specific cognitive domains.","Aged;Aged, 80 and over;Brain/ anatomy & histology/ physiology;Cognition/ physiology;Demography;Educational Status;Executive Function/physiology;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging/methods;Male;Memory/physiology;Neuropsychological Tests;Regression Analysis;Verbal Learning/physiology","Kaplan, R. F.;Cohen, R. A.;Moscufo, N.;Guttmann, C.;Chasman, J.;Buttaro, M.;Hall, C. H.;Wolfson, L.",2009,Oct,10.1080/13803390802635174,0,
3476,Leukoaraiosis. A Short Review,"Leukoaraiosis (LA) is the widely accepted definition for the changes in the white matter of the brain frequently detected in the elderly by neuroimaging techniques. LA has a vascular pathogenesis and is a definite contributory factor for stroke, cognitive decline and dementia. Theoretically, though not yet in practice, if these lesions are detected at an early stage treatment can be instituted promptly, thereby preventing a catastrophic event later. Here we concisely review the relevant literature and stress the imaging of",,"Kapilamoorthy, T. R.;Fiorelli, M.;Gupta, A. K.;Kesavadas, C.;Krishnamoorthy, T.;Bozzao, L.",2005,Apr,,0,
3477,Concepts on the prognostic significance of white matter changes,"Magnetic resonance imaging white matter changes are a common observation in the elderly. The prognostic significance of such abnormalities is incompletely understood. Correlative studies which are reviewed here, suggested a predictive potential of white matter abnormalities for ischemic stroke, intracerebral hemorrhage, cognitive decline or even dementia. According to current review of literature the most compelling evidence for such a relationship exists for intellectual dysfunction. So far, there exist only preliminary data on the rate of WMH progression, but these demonstrate, at least some increase in number or extent within relatively short observational periods.",,"Kapeller, P.;Schmidt, R.",1998,1998,,0,
3478,"Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons","There is growing evidence suggesting that vascular pathologies and dysfunction play a critical role in cognitive impairment, clinical Alzheimer's disease, and dementia. Vascular pathologies such as macroinfarcts, microinfarcts, microbleeds, small and large vessel cerebrovascular disease, and white matter disease are common especially in the brains of older persons where they contribute to cognitive impairment and lower the dementia threshold. Vascular dysfunction resulting in decreased cerebral blood flow, and abnormalities in the blood brain barrier may also contribute to the Alzheimer's disease (AD) pathophysiologic process and AD dementia. This review provides a clinical-pathological perspective on the role of vessel disease, vascular brain injury, alterations of the neurovascular unit, and mixed pathologies in the Alzheimer's disease pathophysiologic process and Alzheimer's dementia. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.",biological marker;Alzheimer disease;arteriolosclerosis;article;atherosclerosis;blood brain barrier;brain blood flow;brain hemorrhage;brain injury;cardiovascular risk;cerebrovascular disease;cognitive defect;dementia;disease course;functional magnetic resonance imaging;human;multiinfarct dementia;priority journal;risk reduction;vascular amyloidosis;white matter lesion,"Kapasi, A.;Schneider, J. A.",2016,,,0,
3479,"Risk of dementia in MCI: combined effect of cerebrovascular disease, volumetric MRI, and 1H MRS","OBJECTIVE: To investigate the combined ability of hippocampal volumes, 1H magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to predict the risk of progression to dementia in mild cognitive impairment (MCI). METHODS: We identified 151 consecutively recruited subjects with MCI from the Mayo Clinic Alzheimer's Disease Research Center and Patient Registry who underwent MRI and 1H MRS studies at baseline and were followed up with approximately annual clinical examinations. A multivariable proportional hazards model that considered all imaging predictors simultaneously was used to determine whether hippocampal volumes, posterior cingulate gyrus 1H MRS metabolites, white matter hyperintensity load, and presence of cortical and subcortical infarctions are complementary in predicting the risk of progression from MCI to dementia. RESULTS: Seventy-five subjects with MCI progressed to dementia by last follow-up. The model that best predicted progression to dementia included age, sex, hippocampal volumes, N-acetylaspartate (NAA)/creatine (Cr) on 1H MRS, and cortical infarctions. Based on age- and sex-adjusted Kaplan-Meier plots, we estimated that by 3 years, 26% of the MCI patients with normal hippocampal volumes, NAA/Cr ratios >1 SD, and no cortical infarctions will progress to dementia, compared with 78% of the MCI patients with hippocampal atrophy, low NAA/Cr (< or =1 SD), and cortical infarction. CONCLUSIONS: Multiple magnetic resonance (MR) markers of underlying dementia pathologies improve the ability to identify patients with prodromal dementia over a single MR marker, supporting the concept that individuals with multiple brain pathologies have increased odds of dementia compared with individuals with a single pathology.","Aged;Aged, 80 and over;Aspartic Acid/analogs & derivatives/analysis/metabolism;Atrophy/etiology/pathology/physiopathology;Biomarkers/analysis/metabolism;Brain/metabolism/pathology/physiopathology;Cerebrovascular Disorders/complications/ diagnosis;Cognition Disorders/ diagnosis/ metabolism/physiopathology;Cohort Studies;Creatine/analysis/metabolism;Dementia/ diagnosis/ metabolism/physiopathology;Disease Progression;Female;Hippocampus/metabolism/pathology/physiopathology;Humans;Magnetic Resonance Imaging/methods;Magnetic Resonance Spectroscopy;Male;Middle Aged;Predictive Value of Tests;Proportional Hazards Models;Risk Factors","Kantarci, K.;Weigand, S. D.;Przybelski, S. A.;Shiung, M. M.;Whitwell, J. L.;Negash, S.;Knopman, D. S.;Boeve, B. F.;O'Brien, P. C.;Petersen, R. C.;Jack, C. R., Jr.",2009,Apr 28,10.1212/WNL.0b013e3181a2e864,0,
3480,MRI and MRS predictors of mild cognitive impairment in a population-based sample,"OBJECTIVE: To investigate MRI and proton magnetic resonance spectroscopy (MRS) predictors of mild cognitive impairment (MCI) in cognitively normal older adults. METHODS: Subjects were cognitively normal older adults (n = 1,156) who participated in the population-based Mayo Clinic Study of Aging MRI/MRS study from August 2005 to December 2010 and had at least one annual clinical follow-up. Single-voxel MRS was performed from the posterior cingulate gyri, and hippocampal volumes and white matter hyperintensity volumes were quantified using automated methods. Brain infarcts were assessed on MRI. Cox proportional hazards regression, with age as the time scale, was used to assess the effect of MRI and MRS markers on the risk of progression from cognitively normal to MCI. Linear mixed-effects models were used to assess the effect of MRI and MRS markers on cognitive decline. RESULTS: After a median follow-up of 2.8 years, 214 participants had progressed to MCI or dementia (estimated incidence rate = 6.1% per year; 95% confidence interval = 5.3%-7.0%). In univariable modeling, hippocampal volume, white matter hyperintensity volume, and N-acetylaspartate/myo-inositol were significant predictors of MCI in cognitively normal older adults. In multivariable modeling, only decreased hippocampal volume and N-acetylaspartate/myo-inositol were independent predictors of MCI. These MRI/MRS predictors of MCI as well as infarcts were associated with cognitive decline (p < 0.05). CONCLUSION: Quantitative MRI and MRS markers predict progression to MCI and cognitive decline in cognitively normal older adults. MRS may contribute to the assessment of preclinical dementia pathologies by capturing neurodegenerative changes that are not detected by hippocampal volumetry.","Aged;Aged, 80 and over;Aging/*pathology/physiology;Female;Humans;*Magnetic Resonance Imaging/methods;*Magnetic Resonance Spectroscopy/methods;Male;Mild Cognitive Impairment/metabolism/*pathology/physiopathology;Predictive Value of Tests;Prodromal Symptoms;Proportional Hazards Models","Kantarci, K.;Weigand, S. D.;Przybelski, S. A.;Preboske, G. M.;Pankratz, V. S.;Vemuri, P.;Senjem, M. L.;Murphy, M. C.;Gunter, J. L.;Machulda, M. M.;Ivnik, R. J.;Roberts, R. O.;Boeve, B. F.;Rocca, W. A.;Knopman, D. S.;Petersen, R. C.;Jack, C. R., Jr.",2013,Jul 9,10.1212/WNL.0b013e31829a3329,0,
3481,Effects of hormone therapy on brain structure in recently postmenopausal women: A randomized controlled trial,"Background: Hormone therapy initiated later in menopause, as in the Women's Health Initiative Memory Study, increases the risk of dementia. Whether or not hormone therapy can preserve neuronal integrity and decrease the risk of dementia when administered early in menopause remains controversial. Non-invasive neuroimaging markers have been suggested as short-term surrogate outcomes to study the effects of menopausal hormone therapy on the brain. We investigated the effects of hormone therapy on brain structure in a randomized, double-blinded placebo-controlled trial in recently postmenopausal women who were of good cardiovascular health. Methods: Participants (age=42-56, within 5-36 months past menopause) in the Kronos Early Estrogen Prevention Study, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50 mg/day transdermal 17beta-estradiol; or 3) placebo pills and patch for 48 months. Oral progesterone (200 mg/day)was given to active treatment groups for 12 days each month. Magnetic resonance imaging (MRI) and cognitive testing were performed in a subset of participants at baseline, and at 18, 36, and 48 months of randomization. Changes in whole brain, ventricular, and white matter hyperintensity (WMH) volumes, and in global cognitive function were measured in women with a baseline and at least one follow-up MRI (n=95). Results: Higher rates of ventricular expansion were detected in the CEE (n=29; p=0.01) and pooled treatment groups (CEE and 17beta-estradiol; n=59; p=0.01), compared to placebo (n=36). Increases in ventricular volume over 18 months of treatment were greater in the CEE group if initiation of hormone therapy occurred later in menopause, after adjusting for age (r=0.40; p=0.03). Rates of WMH increase were higher in the pooled treatment groups compared to placebo (p=0.03). Rates of ventricular expansion correlated with rates of decrease in brain volume (r=-0.58; p=<0.001) and increase in WMH (r=0.27; p=0.01) after adjusting for age. Change in global cognitive function was not different across groups. Conclusions: Ventricular and WMH volumes increased to a greater extent in recently menopausal women given hormone therapy compared to placebo. However, these changes did not affect cognitive performance. Persistence of these imaging changes and their long term effects on cognition remain to be determined.",human;postmenopause;randomized controlled trial;female;brain;hormonal therapy;menopause;cognition;dementia;risk;randomized controlled trial(topic);health;nuclear magnetic resonance imaging;prevention study;follow up;controlled study;white matter;randomization;neuroimaging;pill;memory;transdermal drug administration;brain size;imaging;placebo;estradiol;conjugated estrogen;estrogen;marker;progesterone;Sr-menstr,"Kantarci, K.;Tosakulwong, N.;Lesnick, T. G.;Zuk, S. M.;Gunter, J. L.;Gleason, C. E.;Wharton, W.;Dowling, N. M.;Vemuri, P.;Senjem, M. L.;Shuster, L. T.;Bailey, K. R.;Rocca, W.;Jack Jr, C. R.;Asthana, S.;Miller, V. M.",2015,,,0,
3482,Diffusion tensor imaging and cognitive function in older adults with no dementia,"OBJECTIVE: To determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia. METHODS: We studied older adults without dementia (n = 220) who underwent neuropsychometric testing and a diffusion tensor imaging (DTI) examination at 3 T in a cross-sectional study. Memory, language, attention/executive function, and visual-spatial processing domains were assessed within 4 months of the MRI examination. A fluid-attenuated inversion recovery-based DTI sequence that enabled uncontaminated cortical diffusion measurements was performed. Associations between cortical mean diffusivity (MD) and cognitive function were tested using voxel-based regression analysis. Association between tract diffusivity and cognitive function was tested with regions of interest drawn on color-coded fractional anisotropy (FA) maps. RESULTS: Memory function was associated with the medial temporal lobe cortical MD on voxel-based analysis (p < 0.001, corrected for multiple comparisons), and inferior longitudinal fasciculus and posterior and anterior cingulum FA on tract-based analysis (p < 0.001). Language function was associated with the left temporal lobe cortical MD (p < 0.001, corrected for multiple comparisons), inferior longitudinal fasciculus, fornix, and posterior cingulum FA (p < 0.05). Attention and executive function was associated with the posterior and anterior cingulum FA, and visual-spatial function was associated with posterior cingulum FA (p < 0.01). CONCLUSION: Specific cognitive domain functions are associated with distinct patterns of cortical and white matter diffusivity in elderly with no dementia. Posterior cingulum tract FA was associated with all 4 cognitive domain functions, in agreement with the hypothesis that the posterior cingulate cortex is the main connectivity hub for cognitive brain networks. Microstructural changes identified on DTI may be associated with neurodegenerative pathologies underlying cognitive changes in older adults without dementia.","Aged;Aged, 80 and over;Aging;Anisotropy;Brain Mapping;Cognition Disorders/complications/ pathology;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Language Disorders/etiology/pathology;Male;Memory Disorders/etiology/pathology;Middle Aged;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Space Perception/physiology","Kantarci, K.;Senjem, M. L.;Avula, R.;Zhang, B.;Samikoglu, A. R.;Weigand, S. D.;Przybelski, S. A.;Edmonson, H. A.;Vemuri, P.;Knopman, D. S.;Boeve, B. F.;Ivnik, R. J.;Smith, G. E.;Petersen, R. C.;Jack, C. R., Jr.",2011,Jul 5,10.1212/WNL.0b013e31822313dc,0,
3483,White matter integrity determined with diffusion tensor imaging in older adults without dementia: influence of amyloid load and neurodegeneration,"IMPORTANCE: Pathophysiologic mechanisms leading to loss of white matter integrity and the temporal positioning of biomarkers of white matter integrity relative to the biomarkers of gray matter neurodegeneration and amyloid load in the course of Alzheimer disease (AD) are poorly understood. OBJECTIVE: To investigate the effects of AD-related gray matter neurodegeneration and high beta-amyloid on white matter microstructure in older adults without dementia. DESIGN, SETTING, AND PARTICIPANTS: A population-based, longitudinal cohort study was conducted. Participants included in the Mayo Clinic Study of Aging (N = 701) who underwent magnetic resonance imaging, diffusion tensor imaging (DTI), and positron emission tomography studies with diagnoses of cognitively normal ([CN] n = 570) or mild cognitive impairment ([MCI] n = 131) were included. Both groups were divided into biomarker-negative, amyloid-positive-only, neurodegeneration-positive-only, and amyloid plus neurodegeneration-positive groups based on their amyloid load shown on carbon 11-labeled Pittsburgh Compound B positron emission tomography, AD hypometabolic pattern shown on fludeoxyglucose F 18 positron emission tomography, and/or hippocampal atrophy shown on magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Fractional anisotropy (FA) determined using DTI. RESULTS: No FA alterations were observed in biomarker-negative MCI and amyloid-positive-only CN and MCI groups compared with biomarker-negative CN participants on voxel-based analysis (P < .05; familywise error corrected). Conversely, the neurodegeneration-positive-only and amyloid plus neurodegeneration-positive CN and MCI groups consistently had decreased FA in the fornix, which correlated with cognitive performance (rho = 0.38; P < .001). Patients with MCI had more extensive white matter involvement than did those with CN, and the greatest FA decreases were observed in the amyloid plus neurodegeneration-positive MCI group (P < .05; familywise error corrected). CONCLUSIONS AND RELEVANCE: A high amyloid load does not influence diffusion tensor imaging-based measures of white matter integrity in the absence of coexistent gray matter neurodegeneration in older adults without dementia.","Aged;Aged, 80 and over;Amyloid beta-Peptides/ metabolism;Anisotropy;Biomarkers;Diffusion Tensor Imaging/ methods;Female;Gray Matter/metabolism/ pathology;Humans;Longitudinal Studies;Male;Mild Cognitive Impairment/metabolism/ pathology/physiopathology;Neurodegenerative Diseases/metabolism/ pathology/physiopathology;Positron-Emission Tomography;White Matter/metabolism/ pathology","Kantarci, K.;Schwarz, C. G.;Reid, R. I.;Przybelski, S. A.;Lesnick, T. G.;Zuk, S. M.;Senjem, M. L.;Gunter, J. L.;Lowe, V.;Machulda, M. M.;Knopman, D. S.;Petersen, R. C.;Jack, C. R., Jr.",2014,Dec,10.1001/jamaneurol.2014.1482,0,
3484,"Hippocampal volumes, proton magnetic resonance spectroscopy metabolites, and cerebrovascular disease in mild cognitive impairment subtypes","Background: Although a majority of patients with amnestic mild cognitive impairment (aMCI) progress to Alzheimer disease, the natural history of nonamnestic MCI (naMCI) is less clear. Noninvasive imaging surrogates for underlying pathological findings in MCI would be clinically useful for identifying patients who may benefit from disease-specific treatments at the prodromal stage of dementia. Objective: To determine the characteristic magnetic resonance imaging (MRI) and proton MR spectroscopy ((1)H MRS) profiles of MCI subtypes. Design: Case-control study. Setting: Community-based sample at a tertiary referral center. Patients: Ninety-one patients with single-domain aMCI, 32 patients with multiple-domain aMCI, 20 patients with single- or multiple-domain naMCI, and 100 cognitively normal elderly subjects frequency-matched by age and sex. Main Outcome Measures: Posterior cingulate gyrus (1)H MRS metabolite ratios, hippocampal volumes, and cerebrovascular disease on MRI. Results: Patients with single-domain aMCI were characterized by small hippocampal volumes and elevated ratios of myo-inositol to creatine levels. Patients with naMCI on average had normal hippocampal volumes and (1)H MRS metabolite ratios, but a greater proportion (3 of 20 patients [15%]) had cortical infarctions compared with patients with single-domain aMCI (6 of 91 [7%]). For characterization of MCI subtypes, (1)H MRS and structural MRI findings were complementary. Conclusions: The MRI and (1)H MRS findings in single-domain aMCI are consistent with a pattern similar to that of Alzheimer disease. Absence of this pattern on average in patients with naMCI suggests that cerebrovascular disease and other neurodegenerative diseases may be contributing to the cognitive impairment in many individuals with naMCI. © 2008 American Medical Association. All rights reserved.",,"Kantarci, K.;Petersen, R. C.;Przybelski, S. A.;Weigand, S. D.;Shiung, M. M.;Whitwell, J. L.;Negash, S.;Ivnik, R. J.;Boeve, B. F.;Knopman, D. S.;Smith, G. E.;Jack Jr, C. R.",2008,December,,0,
3485,White-matter integrity on DTI and the pathologic staging of Alzheimer's disease,"Pattern of diffusion tensor MRI (DTI) alterations were investigated in pathologically-staged Alzheimer's disease (AD) patients (n = 46). Patients with antemortem DTI studies and a range of AD pathology at autopsy were included. Patients with a high neurofibrillary tangle (NFT) stage (Braak IV-VI) had significantly elevated mean diffusivity (MD) in the crus of fornix and ventral cingulum tracts, precuneus, and entorhinal white matter on voxel-based analysis after adjusting for age and time from MRI to death (p < 0.001). Higher MD and lower fractional anisotropy in the ventral cingulum tract, entorhinal, and precuneus white matter was associated with higher Braak NFT stage and clinical disease severity. There were no MD and fractional anisotropy differences among the low (none and sparse) and high (moderate and frequent) beta-amyloid neuritic plaque groups. The NFT pathology of AD is associated with DTI alterations involving the medial temporal limbic connections and medial parietal white matter. This pattern of diffusion abnormalities is also associated with clinical disease severity.","Aged;Aged, 80 and over;Aging/pathology;Alzheimer Disease/ diagnostic imaging/ pathology;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Severity of Illness Index;White Matter/ diagnostic imaging/ pathology;Alzheimer's disease;Dti;Limbic tracts;Pathology;White matter","Kantarci, K.;Murray, M. E.;Schwarz, C. G.;Reid, R. I.;Przybelski, S. A.;Lesnick, T.;Zuk, S. M.;Raman, M. R.;Senjem, M. L.;Gunter, J. L.;Boeve, B. F.;Knopman, D. S.;Parisi, J. E.;Petersen, R. C.;Jack, C. R., Jr.;Dickson, D. W.",2017,Aug,,0,
3486,Mild cognitive impairment and Alzheimer disease: regional diffusivity of water,"PURPOSE: To compare the regional diffusivity of water in the brains of normally aging elderly people and patients with mild cognitive impairment (MCI) or Alzheimer disease. MATERIALS AND METHODS: Magnetic resonance images were obtained in 21 patients with Alzheimer disease, 19 patients with MCI, and 55 normally aging elderly control subjects without evidence of cognitive impairment. Regions of interest were drawn to compare the apparent diffusion coefficient (ADC) and the anisotropy index (AI) in frontal, parietal, temporal, occipital, anterior, and posterior cingulate white matter (WM), and the thalami and hippocampi. RESULTS: Hippocampal ADC was higher in MCI and Alzheimer disease patients than in control subjects. ADC of the temporal stem and posterior cingulate, occipital, and parietal WM was higher in Alzheimer disease patients than in control subjects. Except for occipital AI, which was lower in MCI patients than in control subjects, there were no differences in AI among the three groups for any of the regions. CONCLUSION: Hippocampal ADC was significantly different between control subjects and MCI patients, many of whom likely have preclinical Alzheimer disease. Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer disease.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Amnesia/ diagnosis;Anisotropy;Brain/ pathology;Cerebral Cortex/pathology;Diffusion;Female;Gyrus Cinguli/pathology;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Reference Values;Sensitivity and Specificity;Thalamus/pathology","Kantarci, K.;Jack, C. R., Jr.;Xu, Y. C.;Campeau, N. G.;O'Brien, P. C.;Smith, G. E.;Ivnik, R. J.;Boeve, B. F.;Kokmen, E.;Tangalos, E. G.;Petersen, R. C.",2001,Apr,10.1148/radiology.219.1.r01ap14101,0,
3487,"A Japanese family with adrenoleukodystrophy with a codon 291 deletion: A clinical, biochemical, pathological, and genetic report","We report a Japanese family with adrenoleukodystrophy (ALD) with a three base pair deletion (delGAG 291) in the ALD gene. A variety of phenotypes were observed within this family. While the proband (patient 1) was classified as having a rare intermediate type of adult cerebral and cerebello-brain stem forms, his younger brother (patient 2) and nephew (patient 3) had a childhood ALD type. Another nephew (patient 4) of patient 1 was classified as having an adolescent form. The tau level in the cerebrospinal fluid (CSF) in patient 1 was as high as that of patients with Alzheimer's disease (AD). His brain magnetic resonance image (MRI) showed abnormalities in the bilateral cerebellar hemispheres and brain stem, but not in the cerebral white matter, where marked reductions of the cerebral blood flow and oxygen metabolism were clearly demonstrated by positron emission tomography (PET). In patients 2 and 3, the autopsy findings showed massive demyelination of the cerebral white matter with sparing of the U-fibers, compatible with the findings of childhood ALD. Oleic and erucic acids (Lorenzo's Oil) were administered to patients 1 and 4, but sufficient effectiveness was not obtained. The findings in this family suggest that delGAG291 is part of the cause of Japanese ALD with phenotypic variations. Moreover, although the scale of the study is limited, there is a possibility that PET can detect an insidious lesion which is undetectable by computed tomogram (CT) or MRI analysis, and that the higher level of tau reflects the process of neuronal degeneration in ALD. Lorenzo's Oil should be given in the early stage.",,"Kano, S.;Watanabe, M.;Kanai, M.;Koike, R.;Onodera, O.;Tsuji, S.;Okamoto, K.;Shoji, M.",1998,30,,0,
3488,White matter involvement in idiopathic normal pressure hydrocephalus: a voxel-based diffusion tensor imaging study,"The aim of this study was to characterise the white matter damage involved in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI) and the relationship between this damage and clinical presentation. Twenty patients with INPH, 20 patients with Alzheimer's disease and 20 patients with idiopathic Parkinson's disease (as disease control groups) were enrolled in this study. Mean diffusivity (MD) and fractional anisotropy (FA) were determined using DTI, and these measures were analysed to compare the INPH group with the control groups and with certain clinical correlates. On average, the supratentorial white matter presented higher MD and lower FA in the INPH group than in the control groups. In the INPH group, the mean hemispheric FA correlated with some of the clinical measures, whereas the mean hemispheric MD did not. On a voxel-based statistical map, white matter involvement with high MD was localised to the periventricular regions, and white matter involvement with low FA was localised to the corpus callosum and the subcortical regions. The total scores on the Frontal Assessment Battery were correlated with the FA in the frontal and parietal subcortical white matter, and an index of gait disturbance was correlated with the FA in the anterior limb of the left internal capsule and under the left supplementary motor area. DTI revealed the presence of white matter involvement in INPH. Whereas white matter regions with high MD were not related to symptom manifestation, those with low FA were related to motor and cognitive dysfunction in INPH.","Aged;Alzheimer Disease/pathology;Anisotropy;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Hydrocephalus, Normal Pressure/ pathology;Image Interpretation, Computer-Assisted;Male;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/pathology","Kanno, S.;Abe, N.;Saito, M.;Takagi, M.;Nishio, Y.;Hayashi, A.;Uchiyama, M.;Hanaki, R.;Kikuchi, H.;Hiraoka, K.;Yamasaki, H.;Iizuka, O.;Takeda, A.;Itoyama, Y.;Takahashi, S.;Mori, E.",2011,Nov,10.1007/s00415-011-6038-5,0,
3489,Intractable pneumococcal meningoencephalitis associated with a TNF-α antagonist,"A 34-year-old man was treated with a TNF-α antagonist for ankylosing spondylitis, and this subsequently developed a CNS infection. Magnetic resonance imaging showed diffuse subcortical white matter lesions. Streptococcus pneumoniae was cultured from the cerebrospinal fluid and blood. The patient died of multifocal widespread brain damage and subarachnoid hemorrhage, despite intensive antibacterial medication. Pneumococcal meningoencephalitis can occur in association with TNF-α antagonists. Clinicians should be aware of both the risk of fatal bacterial meningoencephalitis associated with TNF-α antagonists and the possibility of an unusual presentation of bacterial meningitis. © 2014 Published by Elsevier B.V.",,"Kang, S. J.;Kim, H. Y.;Kim, Y. S.;Lee, H. N.;Kim, H. T.;Kim, S. H.",2014,15,,0,
3490,"Idiopathic normal-pressure hydrocephalus, cortical thinning, and the cerebrospinal fluid tap test","When considering the underlying pathophysiological mechanisms involved in idiopathic normal pressure hydrocephalus (iNPH), white matter is often the main locus of investigation. However, when an axon in the brain is damaged, degeneration of the neuron can occur proximally (dying back) and Alzheimer's disease (AD), associated with cortical thinning, is a common pathologic comorbidity with iNPH. We investigated differences in cortical thickness between CSF tap test (CSFTT) responders and non-responders in iNPH patients and compared patterns of cortical thickness in iNPH patients with that of AD patients. Thirty-two iNPH patients (16 CSFTT responders and 16 CSFTT non-responders) and 16 AD patients were imaged with MRI, including 3-dimensional volumetric images for cortical thickness analysis across the entire brain. Among the iNPH patients, CSFTT non-responders, when compared to responders, had statistically significant cortical thinning in the left superior frontal gyrus at the level of a false discovery rate (FDR) p < 0.05, and tended to show widespread cortical thinning in most areas of the brain. Relative to the CSFTT responders, AD patients showed statistically significant cortical thinning in superior and medial frontal gyrus, left precentral gyrus, postcentral gyrus, paracentral lobule, precuneus, and superior parietal lobule after FDR correction (p < 0.05). However, comparing patterns of cortical thinning between AD patients and CSFTT non-responders revealed no statistically significant differences. Differences in cortical thickness correlated with CSFTT response for iNPH patients may indicate a possibility for considering patterns of cortical thinning in patients with ventriculomegaly as potential brain imaging markers for the prediction of CSFTT responders. And, our findings suggest that comorbid AD pathology might be related to the cortical thinning patterns found in CSFTT non-responders. Larger studies, using normal controls and combinations of other biomarkers associated with AD, would be necessary to evaluate these hypotheses. © 2013 Elsevier B.V.",,"Kang, K.;Yoon, U.;Lee, J. M.;Lee, H. W.",2013,15,,0,
3491,Diffusion tensor imaging of idiopathic normal-pressure hydrocephalus and the cerebrospinal fluid tap test,"We evaluated relationships between diffusion tensor imaging (DTI) findings and clinical profiles in idiopathic normal-pressure hydrocephalus (INPH) patients, along with differences in DTI parameters between cerebrospinal fluid tap test (CSFTT) responders and non-responders. Fifty-four INPH patients constituted the final group for analysis. Fractional anisotropy (FA), axial diffusivity, radial diffusivity, and mean diffusivity were assessed using atlas-based tract-mapping methods on 20 different fiber tracts. Uncorrected results revealed that CSFTT non-responders, when compared to responders, exhibited lower FA in the left anterior thalamic radiation (ATR), left cingulum-hippocampus (CgH), and left inferior fronto-occipital fasciculus (IFO) and higher axial diffusivity, radial diffusivity, and mean diffusivity in the left CgH and left inferior longitudinal fasciculus (ILF). FA values in the ATR (bilateral), corticospinal tract (right), IFO (bilateral), and ILF (bilateral) were negatively correlated with Unified Parkinson's Disease Rating Scale motor scores. In the right CgH, FA values showed significant positive correlations with Korean-Mini Mental State Examination scores and negative correlations with Clinical Dementia Rating Scale scores. Our findings may suggest a possibility for considering microstructural changes of white matter in patients with ventriculomegaly as potential imaging markers for the prediction of CSFTT responders. Unique patterns of white matter microstructural changes, as measured using DTI, might underlie impairments in distinct symptom domains in patients with INPH.",,"Kang, K.;Yoon, U.;Choi, W.;Lee, H. W.",2016,May 15,10.1016/j.jns.2016.02.067,0,
3492,Abnormal White Matter Integrity in Elderly Patients with Idiopathic Normal-Pressure Hydrocephalus: A Tract-Based Spatial Statistics Study,"We investigated white matter integrity utilizing diffusion tensor imaging in patients with idiopathic normal-pressure hydrocephalus (INPH) who had a positive response to the cerebrospinal fluid tap test and in age- and gender-matched Alzheimer's disease (AD) patients. We enrolled 28 patients with INPH, 28 patients with AD and 20 healthy controls. Tract-based spatial statistics demonstrated that INPH patients had lower fractional anisotropy (FA) in the anterior corona radiate (bilateral), corpus callosum, superior longitudinal fasciculus (bilateral), posterior thalamic radiation (bilateral), external capsule (bilateral) and middle cerebellar peduncle in comparison with the AD and control groups. Volume-of-interest analysis revealed that INPH patients, when compared to the AD and control groups, showed higher mean diffusivity in the anterior corona radiate (bilateral), corpus callosum, superior longitudinal fasciculus (bilateral), posterior thalamic radiation (left), external capsule (bilateral) and middle cerebellar peduncle. And gait dysfunction was significantly correlated with decreased FA in the splenium of the corpus callosum and right external capsule in INPH patients. Our findings may suggest a possibility for considering microstructural changes in white matter integrity in elderly patients as potential imaging markers for differentiation between INPH and AD and may help us understand the potential pathophysiology of gait disturbances associated with INPH.",,"Kang, K.;Choi, W.;Yoon, U.;Lee, J. M.;Lee, H. W.",2016,,10.1159/000443206,0,
3493,Intracranial arterial disease in CADASIL patients,"Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the involvement of cerebral small arteries. Although cerebral large artery disease has been reported in CADASIL patients, the prevalence and location of relevant cerebral arterial disease have not been elucidated. In this study, we aim to characterize infarctions associated with cerebral large artery disease in CADASIL patients. Methods We retrospectively reviewed 49 consecutive symptomatic patients with genetically confirmed CADASIL, who visited the Asan Medical Center between December 2002 and December 2013. Infarctions located within the territory of a relevant, large cerebral artery were identified with the use of magnetic resonance imaging and magnetic resonance angiography. Patients with or without territorial patterns associated with large artery disease were compared. Results Out of a total of 49 patients, 23 patients had cerebral infarction. Among these, seven had infarction associated with cerebral large artery disease. The corresponding vascular lesions were located in the intracranial arteries in all seven patients. There were no differences between patients with or without territorial infarction in terms of vascular risk factors, microbleeds, white matter changes, or mutations involving cysteine. A literature review illustrates that symptomatic intracranial diseases are present in CADASIL patients at least in East Asia. Conclusion Infarction in association with intracranial arterial disease may be a manifestation of CADASIL. Further studies are needed to elucidate the pathologic characteristics and to see whether this occurs exclusively in East Asia.",,"Kang, H. G.;Kim, J. S.",2015,15,,0,
3494,A case of preeclampsia diagnosed with CADASIL after emergency cesarean section,"CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare inherited disease which begins with migraine and later develops repeated cerebral subcortical infarction and dementia We present an anesthetic experience of an undiagnosed CADASIL woman complicated with preeclampsia She developed headache, slurred speech, cognitive dysfunction and restlessness at 35 weeks' gestation and was diagnosed as hypertensive encephalopathy. Urgent cesarean section was decided. After ruling out meningitis by physical examination, and intracranial hemorrhage, cerebral swelling and hydrocephalus by brain CT, spinal anesthesia was chosen. Mild sedation was necessary because the patient became restless and uncooperative during surgery. The anesthetic course was uneventful otherwise. She was either restless or lethargy and had hallucinatory episodes on 1st post-operative day. The neurologist suspected CADASIL because of multiple lacunar infarct lesions on MRI and her family history. The diagnosis was confirmed by skin biopsy and a genetic test.",article;CADASIL;case report;cesarean section;cognitive defect;emergency surgery;family history;female;genetic screening;gestational age;headache;human;human tissue;hypertension encephalopathy;lacunar stroke;nuclear magnetic resonance imaging;preeclampsia;restlessness;sedation;skin biopsy;slurred speech;spinal anesthesia,"Kaneko, H.;Kato, R.;Okutomi, T.;Okamoto, H.",2016,,,0,
3495,Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease,"BACKGROUND: Longitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD. METHODS: Prospective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied. RESULTS: 97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5-34.1; p = 0.015) and dementia (OR 7.03, CI 2.39-25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for ""time to cognitive impairment"" (HR 7.67; CI 3.47-16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting ""time to mild cognitive impairment"" was significant (p = 0.0295). CONCLUSIONS: Hippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.",Adult;Aged;Dementia/*diagnosis/*etiology;Female;Hippocampus/*pathology;Humans;Kaplan-Meier Estimate;Leukoencephalopathies/*etiology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Parkinson Disease/*complications;Predictive Value of Tests;Proportional Hazards Models;Severity of Illness Index;Cerebrovascular disease;Cognition;Hippocampus;Mri;Parkinson's disease,"Kandiah, N.;Zainal, N. H.;Narasimhalu, K.;Chander, R. J.;Ng, A.;Mak, E.;Au, W. L.;Sitoh, Y. Y.;Nadkarni, N.;Tan, L. C.",2014,Nov,10.1016/j.parkreldis.2014.08.024,0,
3496,Frontal subcortical ischemia is crucial for post stroke cognitive impairment,"BACKGROUND: The incidence of post stroke cognitive impairment (PSCI) and predictive factors for PSCI among patients with acute lacunar infarcts is unclear. OBJECTIVE: To study the impact of acute lacunar infarcts and chronic white matter disease in the development of PSCI. METHODS: Prospective cohort study of stroke patients attending a tertiary neurology center. Patients with MRI confirmed acute lacunar infarcts without pre-existing dementia were recruited. Logistic regression was used to determine risk factors for developing PSCI. RESULTS: 145 patients with a mean age of 55.8 years were studied of which 48 patients (33.1%) were identified to have PSCI. Patients with PSCI performed worse on the MMSE, MOCA and FAB and had significantly greater white matter hyperintensity (WMH) in the frontal subcortical (FSC) region (p = 0.006) and higher frontal subcortical acute infarct load (p = 0.002). Logistic regression demonstrated that deep subcortical WMH (odds ratio, OR = 1.45) and acute FSC infarcts (OR = 1.51) were associated with PSCI. High WMH load without acute FSC infarcts was associated with increased risk of PSCI (OR = 4.1). When patients developed acute FSC infarcts on pre-existing severe WMH, the risk of PSCI increased substantially (OR = 11.0). CONCLUSIONS: Patients with acute lacunar infarcts in the FSC region have 1.5 times risk of PSCI. This risk increases substantially to 11 times when there is pre-existing severe white matter disease.","Adult;Aged;Brain Ischemia/*diagnosis/*epidemiology/psychology;Cognition Disorders/*diagnosis/*epidemiology/psychology;Cohort Studies;Female;Humans;Male;Middle Aged;Prospective Studies;Stroke/diagnosis/epidemiology/psychology;Stroke, Lacunar/*diagnosis/*epidemiology/psychology","Kandiah, N.;Wiryasaputra, L.;Narasimhalu, K.;Karandikar, A.;Marmin, M.;Chua, E. V.;Sitoh, Y. Y.",2011,Oct 15,10.1016/j.jns.2011.07.013,0,
3497,Cerebral white matter hyperintensity in Parkinson's disease: a major risk factor for mild cognitive impairment,"BACKGROUND: Mild cognitive impairment (MCI) and dementia contribute to a poor quality of life among patients with PD. The influence of cerebral ischemia as a risk factor for MCI in PD has not been adequately investigated. To address this issue, we examined the influence of the volume and distribution of white matter hyperintensity (WMH) as a risk factor for MCI in early PD. METHODS: Prospective study of patients with early idiopathic PD. All patients had baseline MRI-FLAIR, clinical assessment and detailed neuropsychological evaluation. Data on demographics, vascular risk factors, cognitive performance and WMH volumes were analyzed. RESULTS: 91 patients; mean age 64.9 years, mean education of 10.5 years. 24 patients fulfilled the Movement Disorder Society criteria for MCI and were classified as PD-MCI while the rest were classified as PD with no cognitive impairment (PD-NCI). Patients with PD-MCI and PD-NCI did not differ in Hoehn & Yahr staging. PD-MCI patients had a higher prevalence of diabetes mellitus, hypertension and hyperlipidemia. PD-MCI patients had significantly greater volume of periventricular (6.04 ml vs. 2.66 ml, p = 0.001) and deep subcortical WMH (2.16 vs.1.44, p = 0.002). Regional WMH was significantly greater among PD-MCI in the frontal, parietal and occipital regions. Logistic regression analyses demonstrated WMH to be associated with PD-MCI independent of age, education, and vascular risk factors. Increasing WMH volume was associated with lower performance on executive function, memory and language. CONCLUSIONS: WMH is an important risk factor for PD-MCI independent of vascular risk factors. PD patients with WMH should be regularly screened for MCI.","Aged;Analysis of Variance;Cerebral Cortex/*pathology;Cognition Disorders/*etiology;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;*Parkinson Disease/complications/pathology/psychology;Prospective Studies;Risk Factors","Kandiah, N.;Mak, E.;Ng, A.;Huang, S.;Au, W. L.;Sitoh, Y. Y.;Tan, L. C.",2013,Jul,10.1016/j.parkreldis.2013.03.008,0,
3498,Association between white matter hyperintensity and medial temporal atrophy at various stages of Alzheimer's disease,"BACKGROUND AND PURPOSE: Whilst there is evidence implicating small vessel cerebrovascular disease in the pathogenesis of Alzheimer's disease (AD), its specific contribution to the pathophysiology of AD remains unclear. The burden of small vessel cerebrovascular disease visualized as white matter hyperintensity (WMH) and its association with medial temporal atrophy (MTA) at different stages of AD was studied. METHODS: One hundred and sixty-five cognitively normal (CN) community controls, 103 mild cognitive impairment (MCI) patients, 141 mild AD patients and 68 moderate-severe AD patients were studied. Clinical, cognitive and risk factor data were collected, and WMH and MTA were quantified by trained raters. The Jonckheere-Terpstra test for ordered alternatives was used to study the association between WMH and MTA in different stages of AD. RESULTS: The burden of total WMH increased significantly with increasing severity of AD, even after correcting for confounders. The proportion of CN, MCI, mild AD and moderate-severe AD subjects with severe burden of WMH was 6.7%, 9.7%, 28.4%, and 39.7%, respectively. A strong positive association between WMH severity and MTA was evident amongst MCI (P = 0.011) and mild AD (P = 0.003) subjects, but not in CN (P = 0.953) and moderate-severe AD subjects (P = 0.301). CONCLUSIONS: The burden of WMH increased significantly from the stage of CN to MCI to AD. The association between WMH and MTA was greatest at the stage of MCI and mild AD. This has implications on the strategy to slow the progression of AD, where measures to reduce WMH, including control of vascular risk factors, need to be optimized at the stage of MCI and mild AD.","Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/*pathology;Atrophy/epidemiology/pathology;Cerebral Small Vessel Diseases/epidemiology/*pathology;Comorbidity;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/epidemiology/*pathology;Severity of Illness Index;Singapore/epidemiology;Temporal Lobe/*pathology;White Matter/*pathology;Alzheimer's disease;medial temporal atrophy;white matter hyperintensity","Kandiah, N.;Chander, R. J.;Ng, A.;Wen, M. C.;Cenina, A. R.;Assam, P. N.",2015,Jan,10.1111/ene.12546,0,
3499,Cerebral white matter disease is independently associated with BPSD in Alzheimer's disease,"OBJECTIVES: To study the association between cerebral white matter disease and burden of behavioral and psychological symptoms (BPSD) among patients with moderate to severe AD. METHODS: Patients with moderate to severe AD having undergone MRI brain, cognitive and behavioral evaluations were studied. BPSD was diagnosed based on established clinical guidelines. White matter hyperintensity (WMH) and medial temporal lobe atrophy (MTA) were quantified by a blinded rater. RESULTS: 122 AD patients were studied. Age [76.84 vs. 72.70, p = 0.014] and MMSE [11.69 vs. 15.16, p < 0.001] was significantly higher in patients with BPSD. BPSD patients demonstrated higher periventricular [5.44 vs. 4.21, p < 0.001], deep subcortical [5.07 vs. 3.43, p < 0.001], and total WMH [10.51 vs. 7.65, p < 0.001] compared to non-BPSD patients. Higher proportion of BPSD patients had WMH in the highest tertile of severity (82.22% vs. 45.45%, p < 0.001). After correcting for age, baseline cognition and degree of MTA, total WMH remained significantly associated with a diagnosis of BPSD [odds ratio: 1.45 (1.14-1.85; p = 0.002)]. With severe WMH, the association is significantly increased [odds ratio: 4.3 (1.3-12.5); p = 0.016]. CONCLUSION: WMH is independently associated with BPSD in moderate to severe AD. Optimizing vascular risk factors may be a strategy to reduce the severity of BPSD in AD.",Aged;Alzheimer Disease/ complications;Behavioral Symptoms/ diagnosis/ etiology;Female;Humans;Leukoencephalopathies/ diagnosis;Logistic Models;Male;Mental Status Schedule;Neuropsychological Tests;Retrospective Studies;Temporal Lobe/ pathology,"Kandiah, N.;Chander, R.;Zhang, A.;Yee, C. C.",2014,Feb 15,10.1016/j.jns.2013.11.042,0,
3500,White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration,"INTRODUCTION: Cognitive tests and nonamyloid imaging biomarkers do not consistently identify preclinical AD. The objective of this study was to evaluate whether white matter hyperintensity (WMH) volume, a cerebrovascular disease marker, is more associated with preclinical AD than conventional AD biomarkers and cognitive tests. METHODS: Elderly controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 158) underwent florbetapir-PET scans, psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing. Elderly controls the Parkinson's progression markers initiative (PPMI, n = 58) had WMH volume, cerebrospinal fluid (CSF) Abeta1-42, and APOE status measured. RESULTS: In the ADNI cohort, only WMH volume and APOE epsilon4 status were associated with cerebral Abeta (standardized beta = 0.44 and 1.25, P = .03 and .002). The association between WMH volume and APOE epsilon4 status with cerebral Abeta (standardized beta = 1.12 and 0.26, P = .048 and .045) was confirmed in the PPMI cohort. DISCUSSION: WMH volume is more highly associated with preclinical AD than other AD biomarkers.",Aging;Alzheimer's disease;Amyloid;Leukoaraiosis;Mri;Pet;Preclinical Alzheimer's disease;White matter,"Kandel, B. M.;Avants, B. B.;Gee, J. C.;McMillan, C. T.;Erus, G.;Doshi, J.;Davatzikos, C.;Wolk, D. A.",2016,,10.1016/j.dadm.2016.03.001,0,
3501,"A 78-year-old women with rheumatoid arthritis, right hemiparesis, and renal failure","We report a 78-year old woman with 30 years history of rheumatoid arthritis and nephrotic syndrome, who developed right hemiparesis and renal failure recently. The patient was diagnosed as having rheumatoid arthritis in 1965, and had been treated with gold-sol, steroid hormone, and non-steroidal antiinflammatory drugs intermittently. Later on her clinical course was complicated by nephrotic syndrome, however, her renal function was well compensated. Otherwise, she was apparently doing well until October of 1988 when she had an onset of anomic aphasia; she was 73-year-old at that time. She was admitted to our hospital; a cranial CT scan at that time revealed a low density area in the left temporal region, and she was diagnosed as suffering from an atherothrombotic infarction involving the left middle cerebral artery territory. She recovered soon and was discharged for out patient follow up with ticlopidine 100 mg/day. She was doing well until December 15, 1990, when she had an acute onset of nausea, vomiting, and speech disturbance; she was admitted to our hospital for the second time. On admission, she was alert, but she had motor aphasia, right hemiparesis, and dysarthria. A cranial CT scan revealed a low density area in the left temporal region extending into adjacent frontal and parietal areas including the angular gyrus; in addition, leukoaraiosis, cortical atrophy, and ventricular dilatation were noted. She was treated supportively, and she showed improvement in her aphasia, however, moderate weakness remained in her right upper and lower extremities. She was discharged for out patient follow up. She was doing well until May 21, 1993, when she developed difficulty in swallowing and speech. She became unable to take foods orally and she was admitted again on May 31. On admission, she was a febrile and BP was 120/80 mmHg. General physical examination was unremarkable except for pitting edema and multiple contracture of her joints. On neurologic examination, she was alert but appeared to have aphasia and dementia; she could utter only a few simple words, and was able to understand only simple questions. Evaluation of apraxia and agnosia was impossible. Cranial nerves appeared intact. She was unable to walk because of 'weakness' and contracture. No motor paralysis was present, but detailed muscle strength could not be evaluated. She had no rigidity or spasticity, however, Gegenhalten was noted bilaterally. No abnormal involuntary movement was seen. Deep reflexes were diminished generally, and plantar response was extensor on the leat. She was able to recognize painful stimuli. Pertinent laboratory findings were as follows; WBC 9,600/μl, Ht 34.4%, platelet 194,000/μl, ESR 104 mm/hr, TP 5.0 g/dl, albumin 2.7 g/dl, BUN 87 mg/dl, creatinine 3.86 mg/dl, glucose 87 mg/dl, Na 151 mEq/l, K 6.4 mEq/l, Cl 122 mEq/l, creatinine-clearance 5.6 ml/min, urinary protein 379 mg/dl, and granular cast 3+; liver profile was normal. A cranial CT scan was essentially unchanged compared to the previous one taken at the time of her last admission, in that, a low density area in the left temporal lobe, leukoaraiosis, ventricular dilatation, and fronto-temporal atrophy were noted. She was treated by intravenous fluid with improvement in her dehydration, however, her nephrotic syndrome did not improve. Her clinical course was complicated by bilateral pleural effusion and bronchopneumonia mainly in the right lower lobe. Her pleural effusion increased and ascites was also noted on June 17. She developed respiratory distress, and expired on June 28, 1993. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had nephrotic syndrome due to renal amyloidosis which was caused by rheumatoid arthritis, secondary amyloidosis involving the heart, gastrointestinal tract and peripheral nerves, and large artery thrombosis involving the left middle cerebral artery territory.",corticosteroid;gold salt;nonsteroid antiinflammatory agent;ticlopidine;aged;article;brain infarction;case report;computer assisted tomography;female;hemiparesis;human;kidney failure;nephrotic syndrome;rheumatoid arthritis,"Kanazawa, A.;Hattori, Y.;Ohmuro, H.;Mori, H.;Shirai, T.;Imai, H.;Mizuo, Y.",1994,,,0,
3502,Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with progressive supranuclear palsy,"Objectives: The uncinate fasciculus (UF), a major white-matter tract connecting the frontal and temporal lobes, is related to cognitive/behavioral function. Recently, the UF has been suggested to constitute an indirect pathway of the "" semantic ventral pathway"" in association with the inferior longitudinal fasciculus (ILF). This retrospective study aimed to evaluate damage to the UF and ILF in patients with progressive supranuclear palsy (PSP) using diffusion tensor tract-specific analysis. Material and methods: Diffusion tensor imaging (DTI) of 16 PSP patients with Richardson's syndrome (PSP-RS) and 21 age-matched volunteers were obtained. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values for the bilateral UF and ILF were calculated by tract-specific analysis. Student's t test was used to evaluate the differences between the patients and controls. Also, voxel-based morphometry (VBM) was performed using 3D T1-weighted images to explore the regional atrophy of gray matter in the patients. Results: In patients with PSP-RS, FA of the left UF was significantly decreased compared with the controls, while significant increases in ADC were found in the UF and ILF bilaterally. VBM analysis showed significant clusters of reduced gray matter in the frontal cortex (predominantly in the lateral orbitofrontal cortex, pars opercularis and mesial frontal cortex) and subcortical nuclei (midbrain, caudate and thalamic). Conclusion: This study has shown that patients with PSP-RS had impairment of the UF and ILF. Damage to the UF is thought to be related to atrophy of the orbitofrontal cortex and may possibly be correlated with the cognitive/behavioral impairment seen in PSP. © 2012 Elsevier Masson SAS.",,"Kamiya, K.;Sato, N.;Ota, M.;Nakata, Y.;Ito, K.;Kimura, Y.;Murata, M.;Mori, H.;Kunimatsu, A.;Ohtomo, K.",2013,May,,0,
3503,Diffusional Kurtosis Imaging in Idiopathic Normal Pressure Hydrocephalus: Correlation with Severity of Cognitive Impairment,"PURPOSE: Diffusional kurtosis imaging (DKI) is an emerging technique that describes diffusion of water molecules in terms of deviation from Gaussian distribution. This study investigated correlations between DKI metrics and cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH). MATERIALS AND METHODS: DKI was performed in 29 iNPH patients and 14 age-matched controls. Mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test A (TMT-A) were used as cognitive measures. Tract-based spatial statistics (TBSS) analyses were performed to investigate the between-group differences and correlations with the cognitive measures of the diffusion metrics, including mean kurtosis (MK), fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: In iNPH patients, FA and MK identified positive correlations with cognitive function in similar regions, predominantly in the frontal lobes (P < 0.05, corrected for multiple comparisons). The frontoparietal subcortical white matter showed significant correlations with FAB and TMT-A across more extensive areas in MK analyses than in FA. ADC, AD, and RD analyses showed no significant correlations with MMSE and FAB, while negative correlation with TMT-A was observed in the limited portion of the frontal deep white matter. CONCLUSION: Both FA and MK correlated well with cognitive impairment in iNPH. The observed differences between FA and MK results suggest DKI may play a complementary role to conventional FA and ADC analyses, especially for evaluation of the subcortical white matter.","Aged;Cognitive Dysfunction/ diagnostic imaging/ physiopathology;Dementia/ diagnostic imaging/ physiopathology;Diffusion Tensor Imaging/ methods;Female;Humans;Hydrocephalus, Normal Pressure/ diagnostic imaging/physiopathology;Male;Normal Distribution;White Matter/ physiopathology","Kamiya, K.;Kamagata, K.;Miyajima, M.;Nakajima, M.;Hori, M.;Tsuruta, K.;Mori, H.;Kunimatsu, A.;Arai, H.;Aoki, S.;Ohtomo, K.",2016,Jul 11,,0,
3504,Evaluation of fasudil hydrochloride treatment for wandering symptoms in cerebrovascular dementia with 31P-magnetic resonance spectroscopy and Xe- computed tomography,"This is the first report on the evaluation of treatment with fasudil hydrochloride, a novel intracellular calcium antagonist, for wandering symptoms in patients with cerebrovascular dementia by using 31P-magnetic resonance spectroscopy (MRS) and Xe-computed tomography (CT). The subjects studied were two patients with cerebrovascular dementia who had frequent wandering episodes. The clinical diagnosis was Binswanger-type cerebral infarction in patient 1 and sequelae of cerebral bleeding and multiple lacunar infarctions in patient 2. Treatment with fasudil at 30 or 60 mg/day was given orally for 8 weeks. The wandering symptoms disappeared in both patients during the treatment and reappeared a few days after discontinuation of the treatment. Mental tests indicated that memory was mildly improved during the treatment. Pretreatment 31P-MRS findings revealed decreases in relative signal intensities of phosphomonoester and phosphodiesters and an increase in that of mean adenosine triphosphates. After treatment, these findings disappeared. The regional cerebral blood flow values by Xe-CT in both patients did not show significant changes from before treatment to the values after treatment. These results suggest that the efficacy of fasudil for the wandering symptoms and mental function observed in our patients may have been related to a direct effect on intracellular energy metabolism.",calcium channel blocking agent;fasudil;vasodilator agent;xenon;adult;article;Binswanger encephalopathy;brain blood flow;brain infarction;brain metabolism;case report;cerebrovascular disease;computer assisted tomography;dementia;drug efficacy;human;male;oral drug administration;phosphorus nuclear magnetic resonance;priority journal;symptomatology;treatment outcome;vasodilatation;at 877;ha 1077,"Kamei, S.;Oishi, M.;Takasu, T.",1996,,,0,
3505,"A novel method based on independent component analysis for brain MR image tissue classification into CSF, WM and GM for atrophy detection in Alzheimer's disease","Brain Magnetic Resonance Image (MRI) plays a vital role in diagnosis of diseases like Brain Tumor, Alzheimer, Multiple Sclerosis, Schizophrenia and other White Matter Lesions. In most of the cases accurate segmentation of Brain MRI into tissue types like Cerebro-Spinal Fluid (CSF), White Matter (WM) and Grey Matter (GM) is of interest. The diagnostic accuracy of expert and non-expert Radiologists can be improved with accurate and automated tissue segmentation and classification system. Such system can also be used for trainees to understand the individual tissue distribution in MRI scans. In this paper, we propose a novel automated tissue segmentation and classification method based on Independent Component Analysis (ICA) with Band Expansion Process (BEP) and Support Vector Machine (SVM) classifier which with input as T1, T2 and Proton Density (PD) scans of patient, provides output as CSF, WM and GM indicating the possible atrophy in brain which can help in diagnosis of Alzheimer's disease (AD). The objective of this work is to test the effectiveness of ICA with different input images generated using BEP for accurate brain tissue segmentation by validating results with different quality metrics. The novel method for generating input images for ICA has been implemented and segmented tissues are used for atrophy detection. The BEP + ICA + Thresholding + ‘SVM trained with Grey Level Co-occurrence Matrix (GLCM) based texture features’ is giving 100% tissue classification accuracy for test samples under consideration.",Alzheimer disease;article;band expansion process;brain atrophy;brain tissue;cerebrospinal fluid;classifier;diagnostic accuracy;disease course;gray matter;human;human tissue;independent component analysis;kernel method;neuroimaging;nuclear magnetic resonance imaging;priority journal;quantitative analysis;support vector machine;white matter,"Kamathe, R. S.;Joshi, K. R.",2018,,10.1016/j.bspc.2017.09.005,0,
3506,Relationship between cognitive impairment and white-matter alteration in Parkinson's disease with dementia: tract-based spatial statistics and tract-specific analysis,"OBJECTIVES: We investigated the relationship between white-matter alteration and cognitive status in Parkinson's disease (PD) with and without dementia by using diffusion tensor imaging. METHODS: Twenty PD patients, 20 PDD (Parkinson's disease with dementia) patients and 20 age-matched healthy controls underwent diffusion tensor imaging. The mean diffusivity and fractional anisotropy (FA) map of each patient group were compared with those of the control group by using tract-based spatial statistics. Tractography images of the genu of the corpus callosum fibre tracts were generated, and mean diffusivity and FA were measured. RESULTS: FA values in many major tracts were significantly lower in PDD patients than in control subjects; in the prefrontal white matter and the genu of the corpus callosum they were significantly lower in PDD patients than in PD patients. There was a significant correlation between the Mini-Mental State Examination (MMSE) scores and the FA values of the prefrontal white matter and the genu of the corpus callosum in patients with PD. CONCLUSIONS: Our study shows a relationship between cognitive impairment and alteration of the prefrontal white matter and genu of the corpus callosum. These changes may be useful in assessing the onset of dementia in PD patients. KEY POINTS: * Dementia is a common and important non-motor sign of Parkinson's disease (PD). * The neuropathological basis of dementia in PD is not clear. * DTI shows abnormalities in the prefrontal white matter in PD with dementia. * Prefrontal white matter alteration may be useful biomarker of dementia in PD.","Aged;Anisotropy;Brain/pathology;Brain Mapping/methods;Case-Control Studies;Cognition;Cognition Disorders/ complications;Corpus Callosum/ pathology;Dementia/ diagnosis/ physiopathology;Diffusion Tensor Imaging/methods;Female;Humans;Levodopa/therapeutic use;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/ diagnosis/ physiopathology","Kamagata, K.;Motoi, Y.;Tomiyama, H.;Abe, O.;Ito, K.;Shimoji, K.;Suzuki, M.;Hori, M.;Nakanishi, A.;Sano, T.;Kuwatsuru, R.;Sasai, K.;Aoki, S.;Hattori, N.",2013,Jul,10.1007/s00330-013-2775-4,0,
3507,White matter alteration of the cingulum in Parkinson disease with and without dementia: evaluation by diffusion tensor tract-specific analysis,"BACKGROUND AND PURPOSE: In PD, the neurodegenerative process begins in the brain stem and extends to the limbic system and finally into the cerebral cortex. We used diffusion tensor tractography to investigate the FA of the cingulate fiber tracts in patients with PD with and without dementia. MATERIALS AND METHODS: Fifteen patients with PD, 15 patients with PDD, and 15 age-matched healthy controls underwent diffusion tensor imaging with a 3T MR imager. Diffusion tensor tractography images of the anterior and posterior cingulate fiber tracts were generated. Mean diffusivity and FA were measured along the tractography of the anterior and posterior cingulate fiber tracts. One-way ANOVA with the Scheffe post hoc test was used to compare results among the groups. RESULTS: FA was significantly lower in patients with PDD than in healthy controls in both the anterior and the posterior cingulate fiber tracts (P = .003, P = .015) and significantly lower in patients with PD than in healthy controls (P = .003) in the anterior cingulate fiber tract. There were no significant mean diffusivity differences among the groups. MMSE and FA values of the anterior cingulate fiber tracts in patients with PDD were significantly correlated (r = 0.633, P < .05). CONCLUSIONS: The reduced FA in patients with PD and PDD might reflect neuropathologic changes such as Lewy body pathology in the cingulate fibers. This abnormality might contribute to the dementing process in PD.","Aged;Corpus Callosum/ pathology;Dementia/ complications/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Male;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/ complications/ pathology;Reproducibility of Results;Sensitivity and Specificity","Kamagata, K.;Motoi, Y.;Abe, O.;Shimoji, K.;Hori, M.;Nakanishi, A.;Sano, T.;Kuwatsuru, R.;Aoki, S.;Hattori, N.",2012,May,10.3174/ajnr.A2860,0,
3508,"Vitamin B12 deficiency neurological syndromes: Correlation of clinical, MRI and cognitive evoked potential","Objective: To evaluate cognitive function in B12 deficiency neurological syndromes and response to B12 therapy. Methods: Patients were diagnosed on the basis of low serum B12 or megaloblastic bone marrow or both. Detailed neurological examination was performed and mental status was evaluated by the Mini Mental State Examination (MMSE). Hemoglobin, RBC indices, blood counts, serum chemistry, HIV, thyroid profile, antiparietal cell antibody and craniospinal MRI were done. Cognitive evoked potential was carried out using the odd ball auditory paradigm and recording was achieved from Fz, Cz and Pz referred to mastoid. P3 latency and amplitude were measured and compared with 33 age and sex matched controls. Three months following B12 therapy, clinical and P3 values were reevaluated and compared with the baseline values. Results: 36 patients, aged 16-80 years were included; 32 patients were above 40 years of age. Their median education level was 14 years. The presenting syndrome was myeloneurocognitive in 9, myeloneuropathy in 10, myelocognitive in 8,myelopathy in 8 and only cognitive in 1 patient.MMSE was abnormal in 17; between 28-19 in 14 and 18-11 in 3 patients. Cranial MRI carried out in 14 patients revealed multiple white matter hyperintensity in T2 in 3 and cortical atrophy in 1. P3 was unrecordable in 7 and latency was prolonged in 8 out of 33 patients. P3 latency was significantly prolonged in patients compared to controls and both MMSE and P3 latency improved significantly at the 3-month follow-up. Conclusion: MMSE was abnormal in 47 % and P3 in 45.5% of patients with B12 deficiency neurological syndromes which improved following treatment. Significance: There is high incidence of reversible cognitive impairment and P3 abnormalities in B12 deficiency neurological syndromes. © 2008 Steinkopff-Verlag.",cyanocobalamin;hemoglobin;adolescent;adult;aged;article;blood cell count;brain atrophy;clinical article;cognition;cyanocobalamin deficiency;drug response;evoked auditory response;female;follow up;hemoglobin blood level;human;male;Mini Mental State Examination;neurologic disease;neurologic examination;nuclear magnetic resonance imaging;peripheral neuropathy;priority journal;spinal cord disease;white matter,"Kalita, J.;Misra, U. K.",2008,,,0,
3509,Biomarkers for cognitive dysfunction in Parkinson's disease,"INTRODUCTION: Cognitive dysfunction is among the most prevalent and debilitating non-motor features of Parkinson's disease (PD). The neuropathological correlates of cognitive dysfunction in PD are being revealed by clinicopathological correlation studies. These findings are fostering the development of candidate biomarkers to facilitate diagnosis of cognitive impairment and dementia, and to predict cognitive decline and onset of dementia in PD. METHODS: A literature review of candidate biomarkers for cognitive dysfunction in PD was performed based on a PubMed search for peer-reviewed articles published from 1997 to June 2017 using the search terms ""biomarker"", ""parkinson"", and ""dementia"". RESULTS: Based on the neuropathological correlates of cognitive dysfunction in PD, significant efforts are underway to identify biomarkers that reflect the presence and degree of 1) proteinopathy (i.e., abnormal protein aggregation), 2) neurodegeneration, including neuronal loss and axonal degeneration (i.e., involvement of gray matter and white matter, respectively), 3) neurotransmitter deficiency (e.g., acetylcholine and dopamine), and 4) abnormalities of brain function and connectivity. CONCLUSION: The complexity of multiple substrates of cognitive impairment and dementia in PD will likely preclude the simplicity of a single biomarker. Thus, increased efforts to develop and validate combined biomarkers and predictive algorithms are anticipated.",Biomarker;Csf;Dementia;Mri;Mild cognitive impairment;Neuropathology;Pet;Parkinson,"Kalia, L. V.",2018,Jan,,0,
3510,Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities,"Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect gray matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease. WM glucose delivery and metabolism may have implications for local tissue integrity, and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM. Hypothesizing that affection of oligodendroglia will be associated with loss of glucose uptake, we aimed to investigate glucose metabolism in magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) and normal-appearing WM in patients with and without evidence of amyloid plaques. Subjects with mild cognitive impairment or subjective cognitive decline were included and dichotomized according to pathological (Abeta+) or normal (Abeta-) concentrations of cerebrospinal fluid amyloid-beta 1-42. A total of 50 subjects were included, of whom 30 subjects were classified as Abeta(+) and 20 subjects as Abeta(-). All subjects were assessed with MRI and FDG-PET. FDG-PET images were corrected for effects of partial voluming and normalized to cerebellar WM, before determining WMH FDG-uptake. Although there were no significant differences between the groups in terms of age, WMH volume, number of individual WMHs, or WMH distribution, we found significantly lower (p = 0.021) FDG-uptake in WMHs in Abeta(+) subjects (mean = 0.662, SD = 0.113) compared to Abeta(-) subjects (mean = 0.596, SD = 0.073). There were no significant group differences in the FDG-uptake in normal-appearing WM. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Abeta dysmetabolism and WM pathology in AD.",Alzheimer's disease;Pet;cerebrospinal fluid;cerebrovascular disease;white matter,"Kalheim, L. F.;Selnes, P.;Bjornerud, A.;Coello, C.;Vegge, K.;Fladby, T.",2016,,,0,
3511,White matter hyperintensity microstructure in amyloid dysmetabolism,"Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N = 51), dichotomized according to pathological or normal levels of amyloid-beta peptide (Abeta42) in cerebrospinal fluid (CSF). Thirty-one subjects with low CSF Abeta42 (Abeta+) and 20 subjects with normal CSF Abeta42 (Abeta-) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in Abeta+ relative to Abeta-; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.",0 (Amyloid);0 (Amyloid beta-Peptides);0 (Amyloidogenic Proteins);Aged;Alzheimer Disease;Amyloid/ metabolism;Amyloid beta-Peptides/cerebrospinal fluid;Amyloidogenic Proteins/metabolism;Anisotropy;Case-Control Studies;Cerebrovascular Disorders;Demyelinating Diseases;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Humans;Middle Aged;White Matter/pathology/ ultrastructure;Alzheimer's;cerebrospinal fluid;cognitive impairment;white matter disease,"Kalheim, L. F.;Bjornerud, A.;Fladby, T.;Vegge, K.;Selnes, P.",2017,Jan,,0,3512
3512,White matter hyperintensity microstructure in amyloid dysmetabolism,"Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N = 51), dichotomized according to pathological or normal levels of amyloid-beta peptide (Abeta42) in cerebrospinal fluid (CSF). Thirty-one subjects with low CSF Abeta42 (Abeta+) and 20 subjects with normal CSF Abeta42 (Abeta-) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in Abeta+ relative to Abeta-; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.",,"Kalheim, L. F.;Bjornerud, A.;Fladby, T.;Vegge, K.;Selnes, P.",2016,Jan 20,10.1177/0271678x15627465,0,
3513,MRI in senile dementia: T1 measurement at the level of basal ganglia,"Fourteen patients with senile dementia were studied with a 0.1 Tesla resistive MR scanner. We measured T1 values of 20 areas at the level of basal ganglia and compared with those of 20 normal controls. T1 values were calculated with a 0.2-sec TD and 1.0 TR. Mean T1 values were significantly longer bilaterally in the posterior limb of internal capsule, frontal gray matter, frontal white matter, temporal white matter and occipital white matter in patients with senile dementia.",aged;basal ganglion;case report;central nervous system;computer analysis;diagnosis;human;normal human;nuclear magnetic resonance imaging;relaxation time;senile dementia,"Kakitsubata, Y.",1985,,,0,
3514,123I-N-isopropyl-amphetamine single photon emission computed tomography as a brain imaging technique in dementia,"Because of its binding to specific cerebral amine receptor sites 123I-N-isopropyl-amphetamine (IMP) tracer activity can be used as a measure for the regional cerebral blood flow (rCBF) in the human brain. In 21 psychiatric in-patients an IMP perfusion study was performed using a rotating gamma camera system. The findings at single photon emission computed tomography (SPECT) were compared with different clinical parameters including conventional transmission computed tomography. In SPECT, two different patterns of decrease in IMP uptake could be identified. In patients with a history of cerebrovascular disease SPECT showed asymmetrical, multifocal microcirculatory defects without preference for either hemisphere. In patients with suggested Alzheimer type dementia the perfusion deficits involved the gray and white matter of the parieto-occipital lobes in a bilaterally symmetrical mode with variable extension. Thus, by using IMP-SPECT, it was possible to define the underlying pathologic condition in dementia.","Adult;Aged;Aged, 80 and over;Amphetamines;Brain/radiography/ radionuclide imaging;Dementia/radiography/ radionuclide imaging;Female;Humans;Iodine Radioisotopes;Iofetamine;Male;Middle Aged;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Kaiser-Martini, R.;Kessler, C.;Strauss, L.;Sinn, H.;Kohlmeyer, K.",1986,,,0,
3515,"Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease","INTRODUCTION: Cerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings.RESULTS: In contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature.CONCLUSIONS: Our results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.",,"Kaiser, D.;Weise, G.;Möller, K.;Scheibe, J.;Pösel, C.;Baasch, S.;Gawlitza, M.;Lobsien, D.;Diederich, K.;Minnerup, J.;Kranz, A.;Boltze, J.;Wagner, D. C.",2014,2014,,0,
3516,A case of multiple intracranial cavernous angiomas presented with dementia and Parkinsonism - Clinical and MRI study for 10 years,"We report a case of multiple intracranial cavernous angiomas with serial clinical examination and with MRI imaging for 10 years. The patient, 72 years old woman, had slowly progressive postural tremor and Parkinsonism followed by dementia. Pathological confirmation of cavernous angioma was obtained. At the age of 62, brain MRI study demonstrated hydrocephalus, multiple small hypointensity dots in cerebellum and cerebral white matter, and reticulated cores predominantly adjacent to the ventricles on T(2)-weighted images. Serial MRI imaging shows that the number of small dots has markedly increased and that hypointense lesions surrounding reticulated core, corresponding to hemosidern deposit, have extended. This case indicates that probably due to chronic compression and continuous hemorrhage' multiple and long-standing intracranial lesions could cause dementia and Parkinsonism, which are uncommon symptoms of cavernous angioma.",,"Kageyama, Y.;Kodama, Y.;Yamamoto, S.;Tadano, M.;Ichikawa, K.",2000,2000,,0,
3517,Plasma β-amyloid and MRI markers of cerebral small vessel disease,"Objective: We investigated the relation of circulating plasma b-amyloid (Ab) with MRI markers of small vessel disease (SVD) in dementia-free community persons. Methods: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Ab measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Ab levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n 5 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. Results: Low plasma Ab1-40 levels were associated with increased progression of WMH, and low Ab1-42 with higher odds of extensive WMH progression over the follow-up (odds ratio 5 1.66, 95% confidence interval 5 1.16-2.38). Consistently low Ab1-40 and Ab1-42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE e4 genotype. Conclusion: Progression ofWMH volume in dementia-free older persons is associated with levels of circulating plasma Ab. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.",amyloid beta protein[1-40];amyloid beta protein[1-42];biological marker;aged;aging;article;blood level;blood pressure;brain;cerebrovascular disease;degenerative disease;dementia;disease course;female;follow up;genotype;human;major clinical study;male;nuclear magnetic resonance imaging;priority journal;risk factor;space;very elderly;white matter,"Kaffashian, S.;Tzourio, C.;Soumaré, A.;Dufouil, C.;Zhu, Y.;Crivello, F.;Maillard, P.;Schraen-Maschke, S.;Mazoyer, B.;Buée, L.;Debette, S.",2014,,,0,
3518,Plasma beta-amyloid and MRI markers of cerebral small vessel disease: Three-City Dijon study,"OBJECTIVE: We investigated the relation of circulating plasma beta-amyloid (Abeta) with MRI markers of small vessel disease (SVD) in dementia-free community persons. METHODS: Participants were 1,690 individuals aged 65 to 80 years from the Three-City Dijon Study. Plasma Abeta measurement and MRI examination were performed at baseline and after a 4-year follow-up. MRI markers of SVD included white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces. We examined the relation of plasma Abeta levels with MRI markers of SVD at baseline and with progression of WMH over follow-up (n = 1,057). We also assessed whether these relations were modified by vascular risk factors, notably blood pressure. RESULTS: Low plasma Abeta1-40 levels were associated with increased progression of WMH, and low Abeta1-42 with higher odds of extensive WMH progression over the follow-up (odds ratio = 1.66, 95% confidence interval = 1.16-2.38). Consistently low Abeta1-40 and Abeta1-42 levels on both measurements were associated with accelerated progression of WMH. These associations were modified by blood pressure levels but not the APOE epsilon4 genotype. CONCLUSIONS: Progression of WMH volume in dementia-free older persons is associated with levels of circulating plasma Abeta. These results reinforce the notion of an interrelation of vascular and neurodegenerative mechanisms in cerebral aging.","Aged;Aged, 80 and over;Amyloid beta-Peptides/*blood;Biomarkers/blood;Cerebral Small Vessel Diseases/*blood/*diagnosis/epidemiology;Female;Follow-Up Studies;France/epidemiology;Humans;Longitudinal Studies;Magnetic Resonance Imaging/*trends;Male;Peptide Fragments/*blood","Kaffashian, S.;Tzourio, C.;Soumare, A.;Dufouil, C.;Zhu, Y.;Crivello, F.;Maillard, P.;Schraen-Maschke, S.;Mazoyer, B.;Buee, L.;Debette, S.",2014,Nov 25,10.1212/wnl.0000000000001038,0,
3519,Long-Term Clinical Impact of Vascular Brain Lesions on Magnetic Resonance Imaging in Older Adults in the Population,"BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume and covert brain infarcts are highly prevalent in older adults and are often asymptomatic. We compared the impact of WMH volume and brain infarcts on risk of clinical stroke and dementia in older adults in the population. METHODS: Participants were 1677 individuals aged >/=65 years from the 3-City Dijon study, who were free of stroke and dementia at baseline, followed-up for </=12 years. RESULTS: Both lesion types were comparably associated with an increased risk of stroke (adjusted hazard ratio, 1.72; 95% confidence interval, 1.24-2.40 for WMH volume and hazard ratio, 2.15; 95% confidence interval, 1.18-3.93 for brain infarcts), but only WMH volume was associated with an increased risk of dementia (hazard ratio, 1.41; 95% confidence interval, 1.09-1.83). CONCLUSIONS: The differential impact of WMH and brain infarcts on clinical stroke and dementia suggests relatively different prognostic value of the 2 lesions. WMHs may represent a particularly pertinent magnetic resonance imaging intermediate marker that can be utilized in optimizing prevention strategies for both stroke and dementia in primary care and in trials.","Aged;Aged, 80 and over;Brain Infarction/ diagnostic imaging/ epidemiology;Comorbidity;Dementia/ epidemiology;Female;Follow-Up Studies;France/epidemiology;Humans;Leukoaraiosis/ diagnostic imaging/ epidemiology;Magnetic Resonance Imaging;Male;Stroke/ epidemiology;cerebral small vessel disease;dementia;epidemiology;stroke","Kaffashian, S.;Soumare, A.;Zhu, Y. C.;Mazoyer, B.;Debette, S.;Tzourio, C.",2016,Nov,,1,3520
3520,Long-Term Clinical Impact of Vascular Brain Lesions on Magnetic Resonance Imaging in Older Adults in the Population,"BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume and covert brain infarcts are highly prevalent in older adults and are often asymptomatic. We compared the impact of WMH volume and brain infarcts on risk of clinical stroke and dementia in older adults in the population. METHODS: Participants were 1677 individuals aged >/=65 years from the 3-City Dijon study, who were free of stroke and dementia at baseline, followed-up for </=12 years. RESULTS: Both lesion types were comparably associated with an increased risk of stroke (adjusted hazard ratio, 1.72; 95% confidence interval, 1.24-2.40 for WMH volume and hazard ratio, 2.15; 95% confidence interval, 1.18-3.93 for brain infarcts), but only WMH volume was associated with an increased risk of dementia (hazard ratio, 1.41; 95% confidence interval, 1.09-1.83). CONCLUSIONS: The differential impact of WMH and brain infarcts on clinical stroke and dementia suggests relatively different prognostic value of the 2 lesions. WMHs may represent a particularly pertinent magnetic resonance imaging intermediate marker that can be utilized in optimizing prevention strategies for both stroke and dementia in primary care and in trials.",cerebral small vessel disease;dementia;epidemiology;magnetic resonance imaging;stroke,"Kaffashian, S.;Soumare, A.;Zhu, Y. C.;Mazoyer, B.;Debette, S.;Tzourio, C.",2016,Sep 22,10.1161/STROKEAHA.116.014695,1,
3521,Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer's type,"Almost half of the elderly subjects that are diagnosed with mild cognitive impairment (MCI) go on to develop dementia of Alzheimer's type (DAT) over a 5-year follow-up. MCI and DAT subjects show regional decreases in the volume of brain structures, which correlate with the cognitive decline among these groups. Volumetric changes are found more consistently in the DAT group than in the MCI group. Since not all MCI subjects demonstrate volumetric decline, we propose that the underlying changes in the structural integrity of the brain, measured using magnetization transfer ratio (MTR), may be used as an additional predictor for abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue classification, the brain region of each MR volume was segmented into gray matter and white matter. Mean and standard error of the mean MTR measured within the gray matter was found to be significantly lower in the MCI (30.77 +/-0.29; P = 0.037) and the DAT (29.37 +/-0.41; P = 0.000) group compared to the control group (32.11 +/-0.20). The MTR of white matter was significantly lower only in the DAT group. The gray matter volume was significantly lower (P = 0.000) in the DAT (387.29 +/-26.04 cm(3)) group compared to controls (532.93 +/-20.53 cm(3)) and MCI (464.64 +/-16.93 cm(3)). No significant differences were found in the white matter volume between the three groups. We conclude that changes in MTR are measurable even in the absence of detectable volumetric changes in gray and white matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure for the early diagnosis of dementia of Alzheimer's type.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Brain/ pathology;Cognition Disorders/ diagnosis;Female;Humans;Image Enhancement;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Sensitivity and Specificity","Kabani, N. J.;Sled, J. G.;Chertkow, H.",2002,Mar,10.1006/nimg.2001.0992,0,
3522,Magnetization transfer imaging in 'premanifest' Huntington's disease,"To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in 'premanifest' carriers of the Huntington's disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity.","Adult;Brain/metabolism/ pathology/physiopathology;DNA Mutational Analysis;Disease Progression;Female;Genetic Predisposition to Disease/genetics;Genetic Testing;Heterozygote;Humans;Huntington Disease/ genetics/ pathology/physiopathology;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Mutation/genetics;Nerve Fibers, Myelinated/pathology;Nerve Tissue Proteins/ genetics;Nuclear Proteins/ genetics;Predictive Value of Tests;Prognosis;Sensitivity and Specificity;Severity of Illness Index;Trinucleotide Repeat Expansion/ genetics","Jurgens, C. K.;Bos, R.;Luyendijk, J.;Witjes-Ane, M. N.;van der Grond, J.;Middelkoop, H. A.;Roos, R. A.",2010,Mar,10.1007/s00415-009-5339-4,0,
3523,"Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand","Positron emission tomography (PET) radioligands that bind selectively to beta-amyloid plaques (Abeta) are promising imaging tools aimed at supporting the diagnosis of Alzheimer's disease and the evaluation of new drugs aiming to modify amyloid plaque load. For extended clinical use, there is a particular need for PET tracers labeled with fluorine-18, a radionuclide with 110 min half-life allowing for central synthesis followed by wide distribution. The development of fluorinated radioligands is, however, challenging because of the lipophilic nature of aromatic fluorine, rendering fluorinated ligands more prone to have high non-specific white matter binding. We have here developed the new benzofuran-derived radioligand containing fluorine, AZD4694 that shows high affinity for beta-amyloid fibrils in vitro (K(d) = 2.3 +/- 0.3 nM). In cortical sections from human Alzheimer's disease brain [(3)H]AZD4694 selectively labeled beta-amyloid deposits in gray matter, whereas there was a lower level of non-displaceable binding in plaque devoid white matter. Administration of unlabeled AZD4694 to rat showed that it has a pharmacokinetic profile consistent with good PET radioligands, i.e., it quickly entered and rapidly cleared from normal rat brain tissue. Ex vivo binding data in aged Tg2576 mice after intravenous administration of [(3)H]AZD4694 showed selective binding to beta-amyloid deposits in a reversible manner. In Tg2576 mice, plaque bound [(3)H]AZD4694 could still be detected 80 min after i.v. administration. Taken together, the preclinical profile of AZD4694 suggests that fluorine-18 labeled AZD4694 may have potential for PET-visualization of cerebral beta-amyloid deposits in the living human brain.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/pathology/radionuclide imaging;Amyloid beta-Peptides/ analysis/ metabolism;Animals;Benzofurans/ metabolism;Binding, Competitive/physiology;Female;Fluorine Compounds;Fluorine Radioisotopes;Humans;Hydrocarbons, Fluorinated/ metabolism;Injections, Intraventricular;Male;Mice;Mice, Transgenic;Plaque, Amyloid/metabolism/pathology/ radionuclide imaging;Positron-Emission Tomography/ methods;Radioligand Assay/methods;Rats;Rats, Sprague-Dawley","Jureus, A.;Swahn, B. M.;Sandell, J.;Jeppsson, F.;Johnson, A. E.;Johnstrom, P.;Neelissen, J. A.;Sunnemark, D.;Farde, L.;Svensson, S. P.",2010,Aug,10.1111/j.1471-4159.2010.06812.x,0,
3524,"Cortical atrophy, reduced integrity of white matter and cognitive impairment in subcortical vascular dementia of Binswanger type","AIMS: An association between white matter hyperintensities (WMH) and cognitive dysfunction has long been recognized. However, subjects with identically appearing WMH on magnetic resonance imaging present with a wide variance in cognitive function ranging from normal cognition to dementia. The aim of this study was to compare cortical atrophy and integrity of white matter of patients with subcortical vascular dementia of Binswanger type (SVaD-BT) with those of the normal cognition group with WMH (ncWMH). METHODS: Eleven patients with SVaD-BT and 11 age-, sex-, education- and grade of WMH-matched ncWMH underwent magnetic resonance imaging, including 3-D volumetric images for cortical atrophy and diffusion tensor imaging for integrity of white matter. RESULTS: Compared to ncWMH, SVaD-BT patients showed cortical atrophies in frontal (i.e. frontal pole, precentral gyrus and frontal medial cortex) and occipital areas (i.e. lingual gyrus) followed by atrophies in temporal (i.e. fusiform cortex and middle temporal gyrus) areas. Along with cortical atrophies, reduced integrity with low fractional anisotropy and high mean diffusivity values in genu and splenium of the corpus callosum were detected in SVaD-BT patients. CONCLUSIONS: Our findings suggest that cognitive decline from ncWMH to SVaD-BT may be associated with cortical atrophy and reduced integrity of white matter.","Aged;Atrophy/pathology;Cerebral Cortex/ pathology;Cognition Disorders/etiology/ pathology;Dementia, Vascular/complications/ pathology;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;White Matter/ pathology","Jung, W. B.;Mun, C. W.;Kim, Y. H.;Park, J. M.;Lee, B. D.;Lee, Y. M.;Moon, E.;Jeong, H. J.;Chung, Y. I.",2014,Dec,10.1111/pcn.12196,0,
3525,Automated Classification to Predict the Progression of Alzheimer's Disease Using Whole-Brain Volumetry and DTI,"OBJECTIVE: This study proposes an automated diagnostic method to classify patients with Alzheimer's disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers. METHODS: Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM. RESULTS: Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (+/-13.8), 86.9% (+/-10.5), 96.3% (+/-4.6), and 70.5% (+/-11.5), respectively. CONCLUSION: This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.",,"Jung, W. B.;Lee, Y. M.;Kim, Y. H.;Mun, C. W.",2015,Jan,10.4306/pi.2015.12.1.92,0,
3526,Preservation of neurons of the nucleus basalis in subcortical ischemic vascular disease,"OBJECTIVE: To investigate loss of neurons in the nucleus basalis (NB) of Meynert in patients with subcortical ischemic vascular disease (SIVD) compared with healthy controls, patients with Alzheimer disease (AD), and patients with mixed AD and SIVD. DESIGN: Autopsied cases drawn from a longitudinal observational study of patients with SIVD, patients with AD, and healthy controls. SETTING: Multi center, university-affiliated, program project neuropathology core. PATIENTS: Patients with pathologically defined SIVD (n = 16), AD (n = 20), and mixed AD and SIVD (n = 10) and healthy controls matched by age and educational level (n = 17) were studied. MAIN OUTCOME MEASURES: The NB neuronal cell counts in each group and their correlation with the extent of magnetic resonance imaging white matter lesions and Clinical Dementia Rating (CDR) scores closest to death. RESULTS: No significant loss of neurons was found in SIVD patients compared with age-matched controls in contrast to the AD and mixed groups, who had significant neuronal loss. A significant inverse correlation between NB neurons and CDR scores was found in the AD group but not in the SIVD and mixed groups. The NB cell counts were not correlated with either the extent of white matter lesions or cortical gray matter volume in the SIVD or AD groups. CONCLUSIONS: These findings inveigh against primary loss of cholinergic neurons in SIVD patients but do not rule out the possibility of secondary cholinergic deficits due to disruptions of cholinergic projections to cerebral cortex.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Analysis of Variance;Autopsy;Basal Nucleus of Meynert/ pathology;Case-Control Studies;Cell Count;Cerebrovascular Disorders/complications/ pathology;Cognition Disorders/etiology/pathology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neurons/ pathology;Neuropsychological Tests","Jung, S.;Zarow, C.;Mack, W. J.;Zheng, L.;Vinters, H. V.;Ellis, W. G.;Lyness, S. A.;Chui, H. C.",2012,Jul,10.1001/archneurol.2011.2874,0,
3527,"Associations between Frailty, Retinal Microvascular Changes, and Cerebral White Matter Abnormalities in Korean Older Adults",,aged;Alzheimer disease;atrial fibrillation;brain disease;daily life activity;diabetes mellitus;disease association;frail elderly;geriatric assessment;geriatric patient;human;hypertension;independent living;Korean (people);laboratory test;letter;major clinical study;medical record;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;ophthalmoscopy;physical performance;retina blood vessel;retina disease;survival;university hospital;white matter;white matter injury,"Jung, H. W.;Kim, S. W.;Yoon, S. J.;Choi, J. Y.;Kim, K. I.;Kim, C. H.",2014,,,0,
3528,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a clinicopathological and genetic study of a Swiss family,"This paper reports a Swiss family affected by a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) linked to chromosome 19q12. In three generations several members of this family had recurrent stroke-like episodes and, some developed subcortical dementia, migraine-like headaches, and depression. The clinically affected family members had multiple subcortical infarcts and diffuse leukoencephalopathy on MRI. Necropsy of one patient showed a distinctive non-amyloid and non-atherosclerotic angiopathy of small cerebral and leptomeningeal arteries with concentric depositions of a basophilic granular material replacing the smooth muscle cells of the media. Linkage analysis with five chromosome 19 markers spanning the estimated CADASIL interval showed the absence of any recombinant and positive Lod scores, highly suggestive of linkage of this condition to the CADASIL locus. CADASIL might be an underestimated cause of familial stroke and should be considered in the differential diagnosis of hereditary stroke.",Adult;Brain/pathology;Cerebral Arterial Diseases/genetics/*pathology;Cerebral Arteries/pathology;Cerebral Infarction/*genetics/*pathology;Female;Genetic Linkage;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Pedigree;Switzerland,"Jung, H. H.;Bassetti, C.;Tournier-Lasserve, E.;Vahedi, K.;Arnaboldi, M.;Arifi, V. B.;Burgunder, J. M.",1995,Aug,,0,
3529,"Clinical diagnosis of frontal lobe dementia and Alzheimer's disease: relation to cerebral perfusion, brain atrophy and electroencephalography","The regional cerebral blood flow, brain atrophy, white matter changes and neurophysiologic changes were evaluated in 28 patients with a clinical diagnosis of probable Alzheimer's disease (AD) and in 8 patients with a clinical diagnosis of frontal lobe dementia (FLD) using single photon emission computed tomography, magnetic resonance imaging and electroencephalography (EEG). We found that FLD patients had more severe frontal blood flow reduction and less severe parietal blood flow reduction compared to AD patients. Among patients with mild dementia the EEG changes were less severe in the FLD group. No significant differences were found in white matter changes or in regional atrophy.","Aged;Alzheimer Disease/ diagnosis;Atrophy;Cerebrovascular Circulation;Dementia/ diagnosis;Electroencephalography;Frontal Lobe/blood supply/ pathology;Humans;Magnetic Resonance Imaging;Middle Aged;Regional Blood Flow;Tomography, Emission-Computed, Single-Photon","Julin, P.;Wahlund, L. O.;Basun, H.;Persson, A.;Mare, K.;Rudberg, U.",1995,May-Jun,,0,
3530,SU-E-I-73: Gray Matter Atrophy and White Matter Tract Abnormalities by Voxel Wise Correlation Analysis in Patients with Alzheimer's Disease,"PURPOSE: We evaluated the relationship between white matter (WM) tract disintegration and gray matter (GM) atrophy in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, using diffusion tensor imaging (DTI) and an optimized voxel-based analysis. METHODS: Two hundred thirty one individuals (61 controls, 116 MCI and 54 AD) were included. Voxel-based WM tract statistics was used to obtain whole-brain maps of WM bundles for FA. Voxel-based morphometry (VBM) was conducted to detect regions of gray matter (GM) atrophy in the AD, MCI group relative to the control group. FA maps were processed to make voxel-wise comparison of tract based analysis in whole brain between each the two groups. The relationship between locations of abnormalities in the WM and GM were examined. RESULTS: Patients with AD showed significant GM atrophy in posterior cingulate gyrus (BA31, 32) to the precuneus, the middle temporal lobe (BA19), the superior frontal (BA9) to the anterior cingulate (BA 32), the medial frontal lobe (BA 11, BA25), the hippocampus, the parahippocampal gyrus (BA30/34) and the insula, and WM tract disintegrity of the uncinate fasciculus, posterior cingulate fasciculus and fornix compared with the control and MCI groups. These abnormalities in the AD group were caused by either structural changes in GM atrophy or neural dysfunction due to functional disconnections in the WM tract. CONCLUSIONS: The GM atrophy resulting from WM tract disintegration or GM atrophy itself may be the first step in the AD process, resulting in anatomically congruent correlations between WM disintegration and regional GM atrophy. Using tract based spatial statistics and voxel based analysis, both of which are useful in investigating GM and WM changes in individuals with neurodegenerative disorders.",Brain;Degenerative diseases;Diffusion;Image analysis;Medical imaging;Spatial analysis;Statistical analysis;Tensor methods,"Juh, R.;Suh, T.;Kim, S.",2012,Jun,,0,
3531,Minipig model of Huntington's disease: (1)H magnetic resonance spectroscopy of the brain,"Huntington's disease (HD) is an inherited autosomal neurodegenerative disorder affecting predominantly the brain, characterized by motor dysfunctions, behavioral and cognitive disturbances. The aim of this study was to determine changes in the brain of transgenic minipigs before HD onset using (1)H magnetic resonance (MR) spectroscopy. Measurements were performed on a 3 T MR scanner using a single voxel spectroscopy sequence for spectra acquisition in the white matter and chemical shift imaging sequence for measurement in the striatum, hippocampus and thalamus. A decrease of (phospho)creatine (tCr) concentration was found only in the thalamus (p=0.002) of transgenic minipigs, nevertheless we found significant changes in metabolite ratios. Increase of the ratio choline compounds (tCho)/tCr was found in all examined areas: striatum (p=0.010), thalamus (p=0.011) as well as hippocampus (p=0.027). The ratio N-acetylaspartate+N-acetylaspartylglutamate (tNAA)/tCr (p=0.043) and glutamate+glutamine (Glx)/tCr (p=0.039) was elevated in the thalamus, the ratio myo-inositol (Ins)/tCr (p=0.048) was significantly increased in the hippocampus. No significant differences were observed in the metabolite concentrations in the white matter, however we found significant increase of ratios tNAA/tCr (p=0.018) and tCho/tCr (p=0.003) ratios in transgenic boars. We suppose that the majority of the observed changes are predominantly related to changes in energy metabolism caused by decrease of tCr.","0 (Protons);Animals;Animals, Genetically Modified;Brain/ diagnostic imaging/ metabolism;Disease Models, Animal;Huntington Disease/ diagnostic imaging/ metabolism;Magnetic Resonance Spectroscopy/methods;Male;Protons;Swine;Swine, Miniature","Jozefovicova, M.;Herynek, V.;Jiru, F.;Dezortova, M.;Juhasova, J.;Juhas, S.;Motlik, J.;Hajek, M.",2016,,,0,
3532,Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL,"BACKGROUND AND PURPOSE: Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL. METHODS: Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested. RESULTS: BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (P<0.0001), Mini-Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (P<0.0001), volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages. CONCLUSIONS: In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.",Adult;Aged;Atrophy;Brain/*pathology;Brain Infarction/complications/*pathology;CADASIL/complications/*pathology;Cohort Studies;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies,"Jouvent, E.;Viswanathan, A.;Mangin, J. F.;O'Sullivan, M.;Guichard, J. P.;Gschwendtner, A.;Cumurciuc, R.;Buffon, F.;Peters, N.;Pachai, C.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2007,Jun,10.1161/strokeaha.106.478263,0,
3533,Shape of the central sulcus and disability after subcortical stroke a motor reserve hypothesis,"Background and Purpose-Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. Methods-Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. Results-Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06-1.35; P=0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. Conclusions-The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke.",,"Jouvent, E.;Sun, Z. Y.;De Guio, F.;Duchesnay, E.;Duering, M.;Ropele, S.;Dichgans, M.;Mangin, J. F.;Chabriat, H.",2016,2016,,0,
3534,Apathy is related to cortex morphology in CADASIL. A sulcal-based morphometry study,"OBJECTIVES: Apathy is a debilitating symptom in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the pathophysiology of which remains poorly understood. The aim of this study was to evaluate the neuroanatomic correlates of apathy, using new MRI postprocessing methods based on the identification of cortical sulci, in a large cohort of patients with CADASIL. METHODS: A total of 132 patients with genetically confirmed diagnosis were included in this prospective cohort study. Global cognitive performances were assessed by the Mattis Dementia Rating Scale (MDRS) and disability by the modified Rankin score (mRS). Apathy was defined according to standard criteria. Depth, width, and cortical thickness of 10 large sulci of the frontal lobe in each hemisphere were measured. Logistic regression modeling was used to evaluate the links between apathy and cortical thickness, depth, or width of the different sulci. All models were adjusted for age, gender, level of education, MDRS, mRS, depression, and global brain volume. RESULTS: Complete MRI datasets of high quality were available in 119 patients. Depth of the posterior cingulate sulcus exhibited the strongest association with apathy in fully adjusted models (right: p value = 0.0006; left: p value = 0.004). Depth and width of cortical sulci in mediofrontal and orbitofrontal areas were independently associated with apathy. By contrast, cortical thickness was not. CONCLUSIONS: Cortical morphology in mediofrontal and orbitofrontal areas, by contrast to cortical thickness, is strongly and independently associated with apathy. These results suggest that apathy is related to a reduction of cortical surface rather than of cortical thickness secondary to lesion accumulation in CADASIL.","Adult;Aged;Apathy/*physiology;CADASIL/genetics/*pathology/*physiopathology;Cerebral Cortex/*pathology;Cohort Studies;Female;Gyrus Cinguli/*pathology;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mutation/genetics;Neurologic Examination/methods;Neuropsychological Tests;Receptors, Notch/genetics","Jouvent, E.;Reyes, S.;Mangin, J. F.;Roca, P.;Perrot, M.;Thyreau, B.;Herve, D.;Dichgans, M.;Chabriat, H.",2011,Apr 26,10.1212/WNL.0b013e31821810a4,0,
3535,Intracortical infarcts in small vessel disease: A combined 7-T postmortem MRI and neuropathological case study in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE - The purpose of this study was to report the detection of infarcts of the cerebral cortex in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using high-resolution postmortem 7-T MRI in association with pathological examination. METHODS - Whole brain high-resolution MRI data were obtained postmortem at 7 T in a 53-year-old patient with CADASIL. These MRI data were used to guide the neuropathological examination of the cortex. RESULTS - Combined with neuropathology, MRI allowed the delineation of intracortical infarcts confirmed by histological examination in this case. These lesions were not visible on the last in vivo MRI obtained at 1.5 T and were difficult to detect on neuropathological examination only. CONCLUSIONS - Postmortem high-resolution MRI may help to detect intracortical infarcts in CADASIL and possibly in other small vessel diseases of the brain. © 2011 American Heart Association, Inc.",adult;article;brain cortex lesion;brain infarction;brain region;CADASIL;cadaver;case report;diagnostic imaging;histopathology;human;human tissue;image analysis;immunohistochemistry;male;microangiopathy;neuropathology;nuclear magnetic resonance imaging;priority journal;7-T clinical MRI scanner,"Jouvent, E.;Poupon, C.;Gray, F.;Paquet, C.;Mangin, J. F.;Le Bihan, D.;Chabriat, H.",2011,,,0,
3536,Cortical changes in cerebral small vessel diseases: a 3D MRI study of cortical morphology in CADASIL,"Brain atrophy represents a key marker of disease progression in cerebrovascular disorders. The 3D changes of cortex morphology occurring during the course of small vessel diseases of the brain (SVDB) remain poorly understood. The objective of this study was to assess the changes affecting depth and surface area of cortical sulci and their clinical and radiological correlates in a cohort of patients with cerebral autosomal dominant arteriolopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic SVDB. Data were obtained from a series of 69 CADASIL patients. Validated methods were used to determine depth and surface area of four cortical sulci. The ratio of brain to intracranial cavity volumes (brain parenchymal fraction--BPF), volume of lacunar lesions (LL) and of white matter hyperintensities, number of cerebral microhaemorrhages, and mean apparent diffusion coefficient were also measured. Association between depth and surface area of the cortical sulci and BPF, clinical status and subcortical MRI lesions were tested. Depth and surface area of cortical sulci obtained in 54 patients were strongly correlated with both cognitive score and disability scales. Depth was related to the extent of subcortical lesions, surface area was related only to age. In additional analyses, the depth of the cingular sulcus was independently associated with the volume of LL (P = 0.001), and that of the superior frontal sulcus with the mean apparent diffusion coefficient (P = 0.003). In CADASIL, important morphological changes of cortical sulci occur in association with clinical worsening, extension of subcortical tissue damage and progression of global cerebral atrophy. These results suggest that the examination of cortical morphology may be of high clinical relevance in SVDB.","Adult;Aged;Aging;Brain/pathology;CADASIL/*pathology/psychology;Cerebral Cortex/blood supply/*pathology;Cerebral Ventricles/pathology;Cognition Disorders/pathology;Cohort Studies;Female;Humans;*Image Processing, Computer-Assisted;*Imaging, Three-Dimensional;Linear Models;*Magnetic Resonance Imaging;Male;Middle Aged","Jouvent, E.;Mangin, J. F.;Porcher, R.;Viswanathan, A.;O'Sullivan, M.;Guichard, J. P.;Dichgans, M.;Bousser, M. G.;Chabriat, H.",2008,Aug,10.1093/brain/awn129,0,
3537,Cortical folding influences migraine aura symptoms in CADASIL,"OBJECTIVE: Migraine with aura is a hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In contrast with the majority of CADASIL patients, some affected subjects never experience visual symptoms during their attacks of migraine with aura. The aim of this study was to determine whether specific morphology of the primary visual cortex is associated with the absence of visual symptoms during migraine aura in CADASIL. METHODS: Patients from a large cohort of CADASIL patients, aged <45 years, and with a modified Rankin's scale </=1 were included in the study. Width and depth of the calcarine sulcus in the primary visual cortex as well as cortical thickness in its neighbourhood were compared between patients with visual and those with non-visual migraine auras. RESULTS: 31 patients had visual symptoms (VA group) while nine reported only non-visual symptoms (NVA group) during their migraine auras. Asymmetry index of the calcarine sulcal depth largely differed between the NVA group and the VA group (0.22+/-0.1 vs -0.004+/-0.2; p=1.7x10(-6)). The width of the right calcarine sulcus was significantly lower in the VA group (p=0.04) and cortical thickness was larger in the NVA group (p=0.03). CONCLUSION: The absence of visual symptoms during migraine auras was associated with a profound asymmetry of the primary visual cortex. Aura symptoms seem to be linked to the morphology of the primary visual cortex in CADASIL. This finding potentially reflects more general relationships between spreading depression and cortex morphology in migraine with aura.","Adult;Aged;CADASIL/complications/*pathology;Cerebral Cortex/*pathology;Cohort Studies;Data Interpretation, Statistical;Female;Functional Laterality;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Migraine with Aura/etiology/*pathology;Prospective Studies;Vision Disorders/etiology;Young Adult","Jouvent, E.;Mangin, J. F.;Herve, D.;During, M.;Dichgans, M.;Chabriat, H.",2012,Feb,10.1136/jnnp-2011-300825,0,
3538,Longitudinal changes of cortical morphology in CADASIL,"In CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy), a genetic model of subcortical ischemic vascular dementia (SIVD), clinical status was previously found related to cortex morphology. In the present report, alterations of cortex morphology and their links to clinical worsening were investigated in 190 CADASIL patients followed during 24.4 months. Linear models were used to test relationships between: (1) clinical worsening and changes of depth of cortical sulci and of cortical thickness; (2) alterations of cortical morphology and changes of volume of white matter hyperintensities (WMH(v)) and of lacunar lesions (LL(v)). Reduction of sulcal depth was independently associated with increased time to complete trail making test A and B (p < 0.0001 and p = 0.004) and that of cortical thickness to increased disability (modified Rankin's scale, p = 0.008), while brain atrophy was only related to global cognitive worsening (Mattis dementia rating scale, p = 0.002). The impact of volume of lacunar lesions on cortical alterations was larger than that of volume of white matter hyperintensities. Cortical alterations, mainly related to lacunar lesions, evolve parallel to clinical worsening. These results further support the eventual role of cortical alterations in subcortical ischemic vascular dementia.","Adult;Aged;Aged, 80 and over;Atrophy;CADASIL/*pathology;Cerebral Cortex/*pathology;Dementia, Vascular/*pathology;Disease Progression;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Middle Aged;Models, Neurological;Nerve Fibers, Myelinated/pathology","Jouvent, E.;Mangin, J. F.;Duchesnay, E.;Porcher, R.;During, M.;Mewald, Y.;Guichard, J. P.;Herve, D.;Reyes, S.;Zieren, N.;Dichgans, M.;Chabriat, H.",2012,May,10.1016/j.neurobiolaging.2011.09.013,0,
3539,Part 2: Cerebral amyloid angiopathy and hereditary small vessel diseases of the brain,"Amyloid angiopathy is probably the most frequent non-hypertensive cerebral microangiopathy. Because of its close relationships with Alzheimer's disease, its definition and diagnosis may be difficult. Its clinical and radiological phenotype is quite variable. Other forms of non-hypertensive cerebral microangiopathies have been reported lately with the development of brain MRI. Most of them are of genetic origin. The most frequent, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), is a monogenic disease with eventual devastating clinical consequences affecting young patients. Other forms, particularly of genetic origin, are regularly reported. © 2012 Elsevier Masson SAS.",article;CADASIL;disease association;genetic disorder;human;nuclear magnetic resonance imaging;vascular amyloidosis,"Jouvent, E.;Hervé, D.;Chabriat, H.",2012,,,0,
3540,Prediction of 3-year clinical course in CADASIL,"OBJECTIVE: To obtain simple models predicting disease evolution at 3 years for a given patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: Based on data obtained in a prospective study of 236 patients, we built and validated models predicting, at the individual level, 3-year changes in Mini-Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), Trail Making Test version B (TMTB), and modified Rankin Scale (mRS). These models were based on different sets of predictors obtained at baseline, including either clinical data (epidemiologic data and cardiovascular risk factors) or clinical data and quantitative MRI markers (volume of lacunes [LLV], volume of white matter hyperintensities, normalized brain volume [BPF], number of microbleeds). The Bayesian information criterion (BIC) and the coefficient of determination (R2) were used to determine models with the highest predictive ability and the lowest numbers of predictors. RESULTS: We obtained validated models with a demonstrated ability to predict, for a given patient, 3-year changes in MMSE, MDRS, TMTB, and mRS (R2 on independent samples: 0.22, 0.12, 0.09, and 0.17, respectively). In all cases, the best models according to R2 and BIC values included only the baseline values of the outcome, of BPF, and of LLV. Inclusion of other potential predictors always led to a loss of generalizability. CONCLUSIONS: The prediction of 3-year changes in MMSE, MDRS, TMTB, and mRS for a given patient with CADASIL can be obtained using simple models relying only on the initial values of the considered score, BPF, and LLV.",,"Jouvent, E.;Duchesnay, E.;Hadj-Selem, F.;De Guio, F.;Mangin, J. F.;Herve, D.;Duering, M.;Ropele, S.;Schmidt, R.;Dichgans, M.;Chabriat, H.",2016,Oct 25,,0,
3541,CADASIL mimicking multiple sclerosis: The importance of clinical and MRI red flags,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease, manifesting as recurrent ischaemic events, migraine with aura, behavioural disturbance and cognitive decline. We report two patients with CADASIL masquerading as multiple sclerosis (MS). A 23 year old female presented with a visual scotoma and was discovered to have a corresponding retinal cotton wool spot. MRI brain revealed diffuse T2 hyperintensities suggestive of demyelination. A 56 year old male presented with transient sequential paraesthesia, initially of the perineum followed by the right leg. He also reported memory and mood impairment with a history of migraine with aura. MRI of the brain showed diffuse bilateral white matter lesions with sparing of the anterior temporal poles. Both patients satisfied the modified McDonald diagnostic criteria and were initially thought to have MS. However, they did not satisfy the caveat of “no better explanation” and on subsequent testing NOTCH 3 mutations were identified in both patients [1]. These cases highlight the importance of careful clinical assessment and neuroimaging findings in identifying clinical and paraclinical ‘red-flags’ for a diagnosis other than MS.",beta1a interferon;Notch3 receptor;adult;allodynia;anxiety;article;CADASIL;case report;differential diagnosis;family history;female;frontal lobe;gene mutation;genetic screening;headache;hemiparesis;human;male;memory disorder;middle aged;migraine with aura;mood disorder;multiple sclerosis;nausea;NOTCH3 gene;nuclear magnetic resonance imaging;paresthesia;parietal lobe;photophobia;priority journal;retina disease;retinal cotton wool spot;scotoma;temporal lobe;vomiting;white matter lesion;young adult,"Joshi, S.;Yau, W.;Kermode, A.",2017,,10.1016/j.jocn.2016.09.025,0,
3542,Voxel-based morphometry in autopsy proven PSP and CBD,"The aim of this study was to compare the patterns of grey and white matter atrophy on MRI in autopsy confirmed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and to determine whether the patterns vary depending on the clinical syndrome. Voxel-based morphometry was used to compare patterns of atrophy in 13 PSP and 11 CBD subjects and 24 controls. PSP and CBD subjects were also subdivided into those with a dominant dementia or extrapyramidal syndrome. PSP subjects showed brainstem atrophy with involvement of the cortex and underlying white matter. Frontoparietal grey and subcortical grey matter atrophy occurred in CBD. When subdivided, PSP subjects with an extrapyramidal syndrome had more brainstem atrophy and less cortical atrophy than CBD subjects with an extrapyramidal syndrome. PSP subjects with a dementia syndrome had more subcortical white matter atrophy than CBD subjects with a dementia syndrome. These results show regional differences between PSP and CBD that are useful in predicting the underlying pathology, and help to shed light on the in vivo distribution of regional atrophy in PSP and CBD.","Aged;Aged, 80 and over;Autopsy/methods;Basal Ganglia/*pathology;Cerebral Cortex/*pathology;Female;Humans;Imaging, Three-Dimensional/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neurodegenerative Diseases/*pathology;Statistics, Nonparametric;Supranuclear Palsy, Progressive/*pathology","Josephs, K. A.;Whitwell, J. L.;Dickson, D. W.;Boeve, B. F.;Knopman, D. S.;Petersen, R. C.;Parisi, J. E.;Jack, C. R., Jr.",2008,Feb,10.1016/j.neurobiolaging.2006.09.019,0,
3543,Atypical progressive supranuclear palsy with corticospinal tract degeneration,"Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), sporadic multisystem tauopathy, and some forms of frontotemporal dementia with Parkinsonism linked to chromosome 17 are characterized by neuronal and glial lesions accumulating tau protein containing 4 conserved repeats in microtubule-binding domain (4R tau). Corticospinal tract degeneration is not a common feature of 4R tauopathies. Our objective was to describe 12 cases with pathologic features similar to those of PSP but with prominent corticospinal tract degeneration. We reviewed the historical records and neuropathologic evaluation using standardized sampling, immunohistochemistry, semiquantitative analysis, image analysis, and electron microscopy. The mean age at onset and illness duration was 71 and 5.7 years, respectively. Eight cases were female. Eleven cases had clinical evidence of prominent upper motor neuron disease plus extrapyramidal features. There was focal parasagittal cortical atrophy involving motor cortex and degeneration of corticospinal tract with sparing of lower motor neurons like in primary lateral sclerosis. Prominent tau pathology was found in oligodendrocytes in motor cortex, subjacent white matter, and corticospinal tract characterized by globular cytoplasmic filamentous inclusions that were immunoreactive for 4R tau. The clinicopathologic features of these 12 cases expand the spectrum of 4R tauopathies.","Aged;Brain/metabolism/ pathology;Female;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Male;Microscopy, Immunoelectron;Middle Aged;Mutation;Nerve Degeneration/metabolism/ pathology;Nerve Tissue Proteins/genetics;Oligodendroglia/metabolism/pathology;Pyramidal Tracts/metabolism/ pathology;Supranuclear Palsy, Progressive/metabolism/ pathology;tau Proteins/genetics/metabolism","Josephs, K. A.;Katsuse, O.;Beccano-Kelly, D. A.;Lin, W. L.;Uitti, R. J.;Fujino, Y.;Boeve, B. F.;Hutton, M. L.;Baker, M. C.;Dickson, D. W.",2006,Apr,10.1097/01.jnen.0000218446.38158.61,0,
3544,"Memory complaints in a community sample aged 60-64 years: Associations with cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities","Background. Previous research has found that depression is a major cause of memory complaints. However, there is evidence that memory complaints also weakly predict cognitive decline and dementia. The present study examined a range of possible determinants of memory complaints, covering psychiatric and personality factors, medical history, cognitive test performance, and biological risk factors for dementia (APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities). Method: A community survey was carried out with 2546 persons aged 60-64 years living in Canberra and Queanbeyan, Australia. Participants were asked about memory problems which interfered with daily life and whether medical help had been sought. A randomly selected subsample of 476 persons was given a brain MRI scan. Results. Participants with memory complaints were found to have poorer memory test performance, more depression and anxiety symptoms, have higher scores on personality traits involving negative affect, and to have worse physical health. Multivariate analyses showed that measures of cognitive performance did not make a unique contribution to the prediction of memory complaints above that of the other categories of predictors. Those with memory complaints did not differ on any of the biological risk factors for dementia. Conclusion. In a community sample aged 60-64 years, memory complaints were most closely related to psychiatric symptoms, personality characteristics and poor physical health. There was no evidence of brain changes indicating early dementia. © 2004 Cambridge University Press.",apolipoprotein E;adult;amygdaloid nucleus;anamnesis;anxiety disorder;article;Australia;brain size;cognition;community care;controlled study;daily life activity;dementia;depression;disease association;female;genotype;health status;health survey;hippocampus;human;major clinical study;male;memory disorder;mental disease;mental performance;mental test;multivariate analysis;nuclear magnetic resonance imaging;personality;randomization;risk factor;sampling;scoring system;symptomatology;white matter,"Jorm, A. F.;Butterworth, P.;Anstey, K. J.;Christensen, H.;Easteal, S.;Maller, J.;Mather, K. A.;Turakulov, R. I.;Wen, W.;Sachdev, P.",2004,,,0,
3545,Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study,"BACKGROUND AND PURPOSE: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. METHODS: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. RESULTS: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. CONCLUSIONS: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.","Aged;Aged, 80 and over;Albumins/cerebrospinal fluid;Amyloid beta-Protein Precursor/cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Brain/pathology;Brain Diseases/ cerebrospinal fluid/pathology;Cross-Sectional Studies;Female;Humans;Longitudinal Studies;Male;Nerve Fibers, Myelinated/pathology;Neurofilament Proteins/cerebrospinal fluid;Phosphorylation;Protease Nexins;Receptors, Cell Surface;Severity of Illness Index;Spinal Puncture;Sulfoglycosphingolipids/cerebrospinal fluid;tau Proteins/cerebrospinal fluid/metabolism","Jonsson, M.;Zetterberg, H.;van Straaten, E.;Lind, K.;Syversen, S.;Edman, A.;Blennow, K.;Rosengren, L.;Pantoni, L.;Inzitari, D.;Wallin, A.",2010,Mar,10.1111/j.1468-1331.2009.02808.x,0,
3546,Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study,"BACKGROUND/AIMS: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. METHODS: CSF from elderly individuals with WML was analyzed for amyloid markers, total tau, hyperphosphorylated tau, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). RESULTS: 37 subjects (age 73.6 +/- 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). CONCLUSION: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/psychology;Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers;Brain/ pathology;Dementia, Vascular/cerebrospinal fluid/psychology;Demyelinating Diseases/pathology/psychology;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Leukoaraiosis/cerebrospinal fluid/psychology;Linear Models;Magnetic Resonance Imaging;Male;Nerve Degeneration/pathology/psychology;Netherlands/epidemiology;Neuropsychological Tests;Predictive Value of Tests;Socioeconomic Factors;Sulfoglycosphingolipids/ cerebrospinal fluid;tau Proteins/cerebrospinal fluid","Jonsson, M.;Zetterberg, H.;Rolstad, S.;Edman, A.;Gouw, A. A.;Bjerke, M.;Lind, K.;Blennow, K.;Pantoni, L.;Inzitari, D.;Wallin, A.",2012,,10.1159/000341576,0,
3547,Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia,"OBJECTIVE: Cerebral white-matter changes (WMCs) are frequently found in dementia and have been proposed to be related to vascular factors and a certain symptomatological profile. However, few studies have included both vascular factors and a broad spectrum of cognitive, neurological and psychiatric symptoms, easily detectable by the physician in the everyday clinical work. The objective was to study the relationships between WMCs on MRI/CT and neuropsychiatric symptoms and vascular factors in patients with cognitive impairment. METHODS: One hundred and seventy-six patients with Alzheimer's disease, vascular dementia, mixed dementia, and mild cognitive impairment were included. All patients underwent a standardized examination including medical history, clinical examinations, laboratory tests and brain imaging (CT or MRI). The identification and severity degree of WMCs was assessed blindly to clinical findings, using a semi-quantitative scale. For statistical analyses, patients were grouped based on absence or presence of WMCs. Significant variables in bivariate analyses were included as predictors in stepwise multiple logistic regression analyses. RESULTS: Bivariate analyses showed significant associations between WMCs and age, gender, blood pressure, hypertension, ischaemic heart disease and TIA/RIND. Furthermore, there were significant associations between WMCs and apathy, mental slowness, disinhibition, gait disturbance and focal neurologic symptoms. The multivariate logistic model revealed apathy, mental slowness and age as the most consistent predicting factors for WMCs, together with MRI as a radiological method for the detection of WMCs. CONCLUSIONS: The findings indicate that WMCs in patients with dementia are associated with a dysexecutive-related behavioural symptom profile, vascular factors related to small and large vessel diseases and age.","Aged;Apathy;Brain/ pathology/radiography;Cardiovascular Diseases/pathology;Dementia/ pathology/ psychology/radiography;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Tomography, X-Ray Computed","Jonsson, M.;Edman, A.;Lind, K.;Rolstad, S.;Sjogren, M.;Wallin, A.",2010,Jun,10.1002/gps.2379,0,
3548,Brain uptake and organ distribution of 11C from 11C-labeled glucose,"The time course of the distribution of carbon-11 (11C, t1/2 = 20.4 min) in brain after the i.v. administration of 11C-labeled glucose [( 11C]glucose) was studied in an effort to understand and explore its behavior in relation to the known factors concerning the catabolic fate of glucose carbon in the brain. The biodistribution of 11C from [11C]glucose was studied in rats using organ dissection. Human radiation doses were estimated from rat biodistribution data. All the rat organs except the brain cleared with a half time of 30-60 min. The brain showed delayed uptake that plateaued from 20 to 60 min. The 11C distribution in normal, non-ischemic, brain 30 min after intravenously administered [11C]glucose is due to labeled carbon incorporation into amino acids associated with tricarboxylic acid cycle intermediates. External imaging with the Massachusetts General Hospital positron camera, PC I, was performed in dogs and humans and the time course of 11C incorporation was similar to the rat brain results. Regional uptake paralleled known metabolic differences between grey and white matter in normal human volunteers. A patient with progressive dementia had less uptake in an area of decreased perfusion as demonstrated angiographically, suggesting that the image obtained 20 min after tracer administration could be used to detect abnormalities in cerebral metabolism due to pathology.","Adult;Animals;Brain/ metabolism/radionuclide imaging;Brain Diseases/radionuclide imaging;Carbon Radioisotopes/ metabolism;Cysticercosis/complications/radionuclide imaging;Dementia/etiology;Dogs;Glucose/ metabolism;Humans;Radiation Dosage;Rats;Tissue Distribution;Tomography, Emission-Computed","Jones, S. C.;Ackerman, R. H.;Hoop, B., Jr.;Baron, J. C.;Brownell, G. L.;Taveras, J. M.",1983,,,0,
3549,(1)H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia,"Proton magnetic resonance spectroscopy ((1)H-MRS) allows major metabolites to be measured non-invasively in defined regions of the living brain, and can detect biochemical abnormalities where conventional structural imaging appears normal. MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other primary degenerative dementias have been investigated using MRS. Characteristic and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and elevated myo-inositol (ml) in the mesial temporal and parieto-occipital cortex. These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic distributions which reflect early pathological involvement and atrophy patterns in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline-containing compounds (Cho) have also been reported. Similar changes are seen in VaD; mostly in white matter, whereas in AD they predominate in cortical grey matter. The regional distribution of grey matter involvement may differ between AD and other degenerative dementias. Hence, both the nature and anatomic distribution of metabolite abnormalities contribute to diagnostic discrimination with MRS. NAA/ml ratios from short echo time spectra of the posterior cingulate region cortex discriminate reliably between AD subjects, normal individuals and those with VaD, and provides a useful clinical test, as an adjunct to structural imaging. Elevated ml is detected in mild cognitive impairment (MCI) and quantitative metabolite measures correlate with degrees of cognitive impairment in AD; these suggest a possible role for MRS in early diagnosis and for surrogate biochemical markers for monitoring disease progression and therapeutic response.",,"Jones, R. S.;Waldman, A. D.",2004,July,,0,
3550,Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI,"BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The ""in vivo histological"" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.","Adult;Aged;Anisotropy;Brain/blood supply/ pathology;Brain Ischemia/ complications/diagnosis;Dementia, Multi-Infarct/ diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Jones, D. K.;Lythgoe, D.;Horsfield, M. A.;Simmons, A.;Williams, S. C.;Markus, H. S.",1999,Feb,,0,
3551,"White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI","Diffusion-weighted MRI (DW-MRI) has been increasingly used in imaging neuroscience over the last decade. An early form of this technique, diffusion tensor imaging (DTI) was rapidly implemented by major MRI scanner companies as a scanner selling point. Due to the ease of use of such implementations, and the plausibility of some of their results, DTI was leapt on by imaging neuroscientists who saw it as a powerful and unique new tool for exploring the structural connectivity of human brain. However, DTI is a rather approximate technique, and its results have frequently been given implausible interpretations that have escaped proper critique and have appeared misleadingly in journals of high reputation. In order to encourage the use of improved DW-MRI methods, which have a better chance of characterizing the actual fiber structure of white matter, and to warn against the misuse and misinterpretation of DTI, we review the physics of",,"Jones, D. K.;Knösche, T. R.;Turner, R.",2013,June,,0,
3552,Tracer Kinetic Analysis of (S)-18F-THK5117 as a PET Tracer for Assessing Tau Pathology,"Because a correlation between tau pathology and the clinical symptoms of Alzheimer disease (AD) has been hypothesized, there is increasing interest in developing PET tracers that bind specifically to tau protein. The aim of this study was to evaluate tracer kinetic models for quantitative analysis and generation of parametric images for the novel tau ligand (S)-(18)F-THK5117. METHODS: Nine subjects (5 with AD, 4 with mild cognitive impairment) received a 90-min dynamic (S)-(18)F-THK5117 PET scan. Arterial blood was sampled for measurement of blood radioactivity and metabolite analysis. Volume-of-interest (VOI)-based analysis was performed using plasma-input models; single-tissue and 2-tissue (2TCM) compartment models and plasma-input Logan and reference tissue models; and simplified reference tissue model (SRTM), reference Logan, and SUV ratio (SUVr). Cerebellum gray matter was used as the reference region. Voxel-level analysis was performed using basis function implementations of SRTM, reference Logan, and SUVr. Regionally averaged voxel values were compared with VOI-based values from the optimal reference tissue model, and simulations were made to assess accuracy and precision. In addition to 90 min, initial 40- and 60-min data were analyzed. RESULTS: Plasma-input Logan distribution volume ratio (DVR)-1 values agreed well with 2TCM DVR-1 values (R(2)= 0.99, slope = 0.96). SRTM binding potential (BPND) and reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 (R(2)= 1.00, slope approximately 1.00) whereas SUVr70-90-1 values correlated less well and overestimated binding. Agreement between parametric methods and SRTM was best for reference Logan (R(2)= 0.99, slope = 1.03). SUVr70-90-1 values were almost 3 times higher than BPNDvalues in white matter and 1.5 times higher in gray matter. Simulations showed poorer accuracy and precision for SUVr70-90-1 values than for the other reference methods. SRTM BPNDand reference Logan DVR-1 values were not affected by a shorter scan duration of 60 min. CONCLUSION: SRTM BPNDand reference Logan DVR-1 values were highly correlated with plasma-input Logan DVR-1 values. VOI-based data analyses indicated robust results for scan durations of 60 min. Reference Logan generated quantitative (S)-(18)F-THK5117 DVR-1 parametric images with the greatest accuracy and precision and with a much lower white-matter signal than seen with SUVr70-90-1 images.",,"Jonasson, M.;Wall, A.;Chiotis, K.;Saint-Aubert, L.;Wilking, H.;Sprycha, M.;Borg, B.;Thibblin, A.;Eriksson, J.;Sorensen, J.;Antoni, G.;Nordberg, A.;Lubberink, M.",2016,Apr,10.2967/jnumed.115.158519,0,
3553,Early detection of microstructural white matter changes associated with arterial pulsatility,"Increased cerebral blood flow pulsatility is common in vascular dementia and is associated with macrostructural damage to cerebral white matter or leukoaraiosis (LA). In this study, we examine whether cerebral blood flow pulsatility is associated with macrostructural and microstructural changes in cerebral white matter in older adults with no or mild LA and no evidence of dementia. Diffusion Tensor Imaging was used to measure fractional anisotropy (FA), an index of the microstructural integrity of white matter, and radial diffusivity (RaD), a measure sensitive to the integrity of myelin. When controlling for age, increased arterial pulsation was associated with deterioration in both measures of white matter microstructure but not LA severity. A stepwise multiple linear regression model revealed that arterial pulsatility index was the strongest predictor of FA (R = 0.483, adjusted R (2) = 0.220), followed by LA severity, but not age. These findings suggest that arterial pulsatility may provide insight into age-related reduction in white matter FA. Specifically, increased arterial pulsatility may increase perivascular shear stress and lead to accumulation of damage to perivascular oligodendrocytes, resulting in microstructural changes in white matter and contributing to proliferation of LA over time. Changes in cerebral blood flow pulsatility may therefore provide a sensitive index of white matter health that could facilitate the early detection of risk for perivascular white matter damage and the assessment of the effectiveness of preventative treatment targeted at reducing pulsatility.",,"Jolly, T. A.;Bateman, G. A.;Levi, C. R.;Parsons, M. W.;Michie, P. T.;Karayanidis, F.",2013,,10.3389/fnhum.2013.00782,0,
3554,Semantic Dementia Diagnosed by F-18 FDG PET/MRI: Co-registered Images,"We report a case of a 61-year-old male who presented with a sudden change in mental status. From a psychiatric standpoint, his symptoms were consistent with a bipolar disorder. A neurology consult raised suspicion for vascular dementia, given the sudden onset of symptoms; however, the magnetic resonance angiography (MRA) was unremarkable. The magnetic resonance imaging (MRI) had findings that were suggestive of both vascular and frontotemporal lobe dementia based on parenchymal atrophy and a lacunar infarct near the thalamus. However, by co-registering the magnetic resonance images with a subsequent fluorine-18 Fluorodeoxyglucose positron emission tomography (F-18 FDG PET), and combining the functional data with the anatomic appearance, the diagnosis was narrowed to semantic dementia, which is one of the lesser known subtypes of frontotemporal lobe dementia (FTD).",,"Jolepalem, P.;Wu, D.",2013,,10.4103/2156-7514.117459,0,
3555,Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: The LADIS Study,"Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing - namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.",,"Jokinen, H.;Ryberg, C.;Kalska, H.;Ylikoski, R.;Rostrup, E.;Stegmann, M. B.;Waldemar, G.;Madureira, S.;Ferro, J. M.;Van Straaten, E. C. W.;Scheltens, P.;Barkhof, F.;Fazekas, F.;Schmidt, R.;Carlucci, G.;Pantoni, L.;Inzitari, D.;Erkinjuntti, T.",2007,May,,0,
3556,Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study,"OBJECTIVE: To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance. METHODS: A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders. RESULTS: MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes. CONCLUSIONS: Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline.","Aged;Aged, 80 and over;Atrophy/complications;Brain/*pathology;Cerebral Small Vessel Diseases/*complications/pathology;Cross-Sectional Studies;Dementia, Vascular/etiology/*pathology;Female;Humans;Linear Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/etiology/*pathology;Neuropsychological Tests;Prospective Studies;Temporal Lobe/pathology","Jokinen, H.;Lipsanen, J.;Schmidt, R.;Fazekas, F.;Gouw, A. A.;van der Flier, W. M.;Barkhof, F.;Madureira, S.;Verdelho, A.;Ferro, J. M.;Wallin, A.;Pantoni, L.;Inzitari, D.;Erkinjuntti, T.",2012,May 29,10.1212/WNL.0b013e3182583070,0,
3557,Longitudinal cognitive decline in subcortical ischemic vascular disease -the ladis study,"Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function. © 2009 S. Karger AG, Basel.",,"Jokinen, H.;Kalska, H.;Ylikoski, R.;Madureira, S.;Verdelho, A.;Van Der Flier, W. M.;Scheltens, P.;Barkhof, F.;Visser, M. C.;Fazekas, F.;Schmidt, R.;O'Brien, J.;Waldemar, G.;Wallin, A.;Chabriat, H.;Pantoni, L.;Inzitari, D.;Erkinjuntti, T.",2009,April,,0,
3558,Medial temporal lobe atrophy and memory deficits in elderly stroke patients,"Medial temporal lobe atrophy (MTA) and its role in memory deficits have been studied extensively in patients with various dementias and non-degenerative neurologic diseases. In stroke patients MTA is a significant risk factor for dementia. However, its role in memory decline in non-demented stroke patients is not yet known. Our aim was to evaluate the relationship between MTA and cognitive functions in a large cohort of elderly patients, who underwent a comprehensive neuropsychologic examination and magnetic resonance imaging 3 months after an ischemic stroke. The study sample (n = 260) was divided into three groups according to the severity of MTA. After adjusting for age, volume of infarcts and cortical atrophy, we found that patients with moderate to severe MTA performed significantly worse in tests of learning, story recall, visual reproduction, block design and mental speed. In contrast, the groups did not differ in tests of digit span, flexibility, verbal fluency and conceptualization. Our conclusion is that in aged stroke patients, MTA is associated with poor performance in specific cognitive domains. The most vulnerable domains are memory and visuospatial functions, whereas verbal and executive functions seem to be unrelated to MTA.","Aged;Aged, 80 and over;Analysis of Variance;Atrophy;Attention/physiology;Brain Mapping;Chi-Square Distribution;Cross-Sectional Studies;Demography;Female;Humans;Magnetic Resonance Imaging/methods;Male;Memory Disorders/ etiology/ pathology;Middle Aged;Neuropsychological Tests/statistics & numerical data;Problem Solving/physiology;Prospective Studies;Psychomotor Performance/physiology;Retrospective Studies;Stroke/ complications/ pathology;Temporal Lobe/ pathology;Verbal Behavior/physiology","Jokinen, H.;Kalska, H.;Ylikoski, R.;Hietanen, M.;Mantyla, R.;Pohjasvaara, T.;Kaste, M.;Erkinjuntti, T.",2004,Dec,10.1111/j.1468-1331.2004.00870.x,0,
3559,White matter hyperintensities as a predictor of neuropsychological deficits post-stroke,"Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.",,"Jokinen, H.;Kalska, H.;Mäntylä, R.;Ylikoski, R.;Hietanen, M.;Pohjasvaara, T.;Kaste, M.;Erkinjuntti, T.",2005,September,,0,
3560,Early-stage white matter lesions detected by multispectral MRI segmentation predict progressive cognitive decline,"White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a ""pre-visible"" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment.",,"Jokinen, H.;Gonçalves, N.;Vigário, R.;Lipsanen, J.;Fazekas, F.;Schmidt, R.;Barkhof, F.;Madureira, S.;Verdelho, A.;Inzitari, D.;Pantoni, L.;Erkinjuntti, T.",2015,,,0,
3561,"White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease","BACKGROUND: In dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), it is still debated whether white matter hyperintensities (WMH) on MRI reflect atherosclerotic cerebrovascular changes or Alzheimer's disease (AD)-related pathology such as cerebral amyloid angiopathy. To examine AD-related pathology in DLB and PDD, we compared the severity of WMH and medial temporal lobe atrophy among patients with DLB, PDD, non-demented PD (PDND), and AD. METHODS: We retrospectively studied sex- and age-matched outpatients with AD, DLB, PDD, and PDND, as well as subjects without central nervous system disorders as normal controls (n=50 each). All subjects underwent 1.5-T MRI examinations, and WMH detected by T2-weighted images or fluid-attenuated inversion recovery images were semiquantified according to the Fazekas method. Medial temporal lobe atrophy (MTA) was visually assessed by the MTA score. RESULTS: WMH were more prominent in AD, DLB, and PDD patients than in PDND patients and normal controls (NCs). DLB as well as AD showed more severe WMH than PDD. Visual assessment of medial temporal lobe atrophy showed that AD patients had the most severe atrophy, followed by DLB, PDD, and PDND patients, and NC subjects in that order. MTA scores showed significant correlations with WMH severity. CONCLUSION: Our results indicated that DLB was more similar to AD than to PDD in terms of MRI findings, suggesting that WMH in DLB may reflect mainly AD-related pathology rather than atherosclerotic cerebrovascular changes.",Alzheimer's disease;Dementia with Lewy bodies;Mri;Medial temporal lobe atrophy;Parkinson's disease with dementia;White matter hyperintensities,"Joki, H.;Higashiyama, Y.;Nakae, Y.;Kugimoto, C.;Doi, H.;Kimura, K.;Kishida, H.;Ueda, N.;Nakano, T.;Takahashi, T.;Koyano, S.;Takeuchi, H.;Tanaka, F.",2018,Feb 15,,0,
3562,A case of neurosarcoidosis with labyrinthine involvement,"Sarcoidosis is a chronic granulomatous disease of unknown aetiology, which may involve any organ system. It most commonly occurs in adults with childhood involvement being rare. Central nervous system involvement is seen in up to 25% and typically involves meningeal disease resulting in multiple cranial neuropathies. Other common clinical findings include seizures, headache, dementia, and pituitary dysfunction. Imaging plays a central role in the diagnosis with typical findings including pachymeningeal and leptomeningeal enhancing lesions. Other imaging findings include lacunar and major territory infarcts, hypothalamic and infundibular thickening, hydrocephalus, and cranial nerve enhancement. We present a case of an eight-year-old male patient with progressive headache, visual disturbance, unilateral sensory hearing loss, and multiple cranial neuropathies. Imaging findings demonstrated the classic pachymeningeal and leptomeningeal enhancement along much of the skull base, as well as enhancement of the right and left second and eighth cranial nerves. Extensive inflammatory changes were noted in the temporal bones and paranasal sinuses. There was also enhancement of the right and left labyrinths. Sinus biopsy confirmed sarcoidosis. We present the first case to our knowledge of sarcoid labyrinthitis.",,"Johnson, P. B.;Melbourne-Chambers, R.;Saindane, A. M.;Desai, N.;Smith, M.",2014,,10.1155/2014/530431,0,
3563,Comparison of magnetic resonance and roentgen ray computed tomography in dementia,"To compare the merits of magnetic resonance imaging (MRI) and roentgen ray computed tomography (CT) in assessing patients with dementia, we examined pairs of MR and CT brain images obtained from 26 patients with Alzheimer's disease (AD), eight patients with vascular or mixed dementia, and two patients with Parkinson's disease plus dementia. Magnetic resonance and CT images were independently rated on a qualitative scale of 0 (normal) to 3 (severely abnormal) in 39 separate brain regions. Ratios of anterolateral and third ventricular linear spans to linear skull spans were measured. Abnormalities in subcortical white matter and in hippocampus, enlargement of basal and sylvian cisterns, and ventriculomegaly were more evident on MR than CT scans, but qualitative ratings in all other brain regions were similar. Linear ventricular span ratios based on MR images did not differ significantly from those measured on CT. White matter abnormalities on MR were high signal foci on T2-weighted images whose pathologic substrate was uncertain; in a single case studied pathologically, no abnormalities were detected in brain regions that contained high signal foci. Dementia severity correlated with periventricular white matter abnormalities on both MR and CT images.",,"Johnson, K. A.;Davis, K. R.;Buonanno, F. S.;Brady, T. J.;Rosen, T. J.;Growdon, J. H.",1987,Oct,,0,
3564,Diagnostic utility of cerebral white matter integrity in early Alzheimer's disease,"We compared white matter integrity with brain atrophy in healthy controls and participants with very mild dementia (Clinical Dementia Rating 0 vs. 0.5) from the Brain Aging Project, a longitudinal study of aging and memory at the University of Kansas Medical Center. Structural magnetic resonance imaging and diffusion tensor imaging (DTI) including fractional anisotropy and mean diffusivity were performed on 27 patients with very mild dementia (Clinical Dementia Rating = 0.5) of the Alzheimer's type (DAT), and 32 cognitively normal subjects. Patient groups were compared across 6 volumetric measures and 14 DTI regions of interest. Very mildly demented patients showed expected disease-related patterns of brain atrophy with reductions in whole-brain and hippocampal volumes most prominent. DTI indices of white matter integrity were mixed. Right parahippocampus showed significant but small disease-related reductions in fractional anisotropy. Right parahippocampus and left internal capsule showed greater mean diffusivity in early DAT compared with controls. A series of discriminant analyses demonstrated that gray matter atrophy was a significantly better predictor of dementia status than were DTI indices. Brain atrophy was most strongly related to very mild DAT. Modest disease-related white matter anomalies were present in temporal cortex, and deep white matter had limited discriminatory diagnostic power, probably because of the very mild stage of disease in these participants.","Aged;Alzheimer Disease/complications/ diagnosis;Anisotropy;Brain Mapping;Case-Control Studies;Cerebral Cortex/ pathology;Cognition Disorders/ diagnosis/etiology;Cohort Studies;Diffusion Magnetic Resonance Imaging/methods;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Retrospective Studies","Johnson, D. K.;Barrow, W.;Anderson, R.;Harsha, A.;Honea, R.;Brooks, W. M.;Burns, J. M.",2010,Aug,10.3109/00207454.2010.494788,0,
3565,Midlife psychological distress associated with late-life brain atrophy and white matter lesions: a 32-year population study of women,"OBJECTIVE: Long-standing psychological distress increases the risk of dementia, especially Alzheimer's disease. The present study examines the relationship between midlife psychological distress and late-life brain atrophy and white matter lesions (WMLs), which are common findings on neuroimaging in elderly subjects. METHODS: A population-based sample of 1462 women, aged 38 to 60 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, and 2000. Computed tomography (CT) of the brain was done in 379 survivors in 2000, and of those, 344 had responded to a standardized question about psychological distress in 1968, 1974, and 1980. WMLs, cortical atrophy, and central atrophy (ventricular sizes) were measured at CT scans. RESULTS: Compared with women reporting no distress, those reporting frequent or constant distress at one examination or more (in 1968, 1974, and 1980) more often had moderate-to-severe WMLs (multiadjusted odds ratio = 2.39, 95% confidence interval = 1.16-4.92) and moderate-to-severe temporal lobe atrophy (multiadjusted odds ratio = 2.51, 95% confidence interval = 1.04-6.05) on brain CT in 2000. Frequent/constant distress was also associated with central brain atrophy, that is, higher bicaudate ratio, higher cella media ratio, and larger third-ventricle width. CONCLUSIONS: Long-standing psychological distress in midlife increases risks of cerebral atrophy and WMLs on CT in late life. More studies are needed to confirm these findings and to determine potential neurobiological mechanisms of these associations.","Adult;Age Factors;Atrophy/epidemiology/radiography;Brain/*pathology/radiography;Brain Diseases/*epidemiology/pathology;Chronic Disease;Confounding Factors (Epidemiology);Dementia/*epidemiology/pathology;Female;Humans;Linear Models;Middle Aged;*Population Surveillance;Stress, Psychological/*epidemiology/pathology;Sweden/epidemiology;Temporal Lobe/pathology/radiography;Tomography, X-Ray Computed;*Women's Health","Johansson, L.;Skoog, I.;Gustafson, D. R.;Olesen, P. J.;Waern, M.;Bengtsson, C.;Bjorkelund, C.;Pantoni, L.;Simoni, M.;Lissner, L.;Guo, X.",2012,Feb-Mar,10.1097/PSY.0b013e318246eb10,0,
3566,Dementia with impaired temporal glucose metabolism in late-onset metachromatic leukodystrophy,"An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism. Copyright © 2001 S. Karger AG, Basel.",,"Johannsen, P.;Ehlers, L.;Hansen, H. J.",2001,2001,,0,
3567,Angiotensin-converting enzyme in cerebrospinal fluid and risk of brain atrophy,"BACKGROUND: Higher angiotensin-converting enzyme (ACE) activity might increase the risk of Alzheimer's disease by increasing blood pressure, and subsequent development of cerebral small vessel disease (CSVD). Yet, it may also decrease this risk, as it functions to degrade amyloid-beta, thereby reducing brain atrophy. OBJECTIVE: To examine the cross-sectional associations of serum and cerebrospinal fluid (CSF) ACE protein levels and activity with brain atrophy and CSVD in a memory clinic cohort. METHODS: In 118 subjects from the memory clinic based Amsterdam Dementia Cohort (mean age 66 +/- 8 years), ACE protein levels (ng/ml) and activity in CSF and serum were investigated. Poisson regression analyses were used to associate ACE measurements with rated global cortical atrophy, medial temporal lobe atrophy, lacunar infarcts, white matter hyperintensities, and microbleeds on brain MRI. RESULTS: Higher CSF ACE activity was associated with a reduced risk of global brain atrophy. The relative risk (95% CI) of having global cortical atrophy >/=2 per SD increase in CSF ACE activity was 0.67 (0.49; 0.93). ACE levels were not significantly related to measures of CSVD. CONCLUSIONS: These results show that high ACE might have protective effects on the brain. This could suggest that ACE inhibitors, which may lower CSF ACE levels, are not preferred as antihypertensive treatment in patients at risk for Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/blood/*cerebrospinal fluid/*pathology;Apolipoproteins E/genetics;Atrophy/cerebrospinal fluid/pathology;Brain/*pathology;Brain Diseases/blood/*cerebrospinal fluid/*pathology;Cerebral Small Vessel Diseases/enzymology;Female;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/cerebrospinal fluid/etiology;Middle Aged;Peptidyl-Dipeptidase A/blood/*cerebrospinal fluid;Alzheimer's disease;angiotensin-converting enzyme;brain atrophy;cerebral small vessel disease;hypertension","Jochemsen, H. M.;van der Flier, W. M.;Ashby, E. L.;Teunissen, C. E.;Jones, R. E.;Wattjes, M. P.;Scheltens, P.;Geerlings, M. I.;Kehoe, P. G.;Muller, M.",2015,,10.3233/jad-131496,0,
3568,Angiotensin-converting enzyme and progression of white matter lesions and brain atrophy--the SMART-MR study,"High levels of angiotensin-converting-enzyme (ACE) may increase the risk of dementia through blood pressure elevation and subsequent development of cerebral small-vessel disease. However, high ACE levels may also decrease this risk through amyloid degradation which prevents brain atrophy. Within the SMART-MR study, a prospective cohort study among patients with symptomatic atherosclerotic disease, serum ACE levels were measured at baseline and a 1.5 Tesla brain MRI was performed at baseline and after on average (range) 3.9 (3.0-5.8) years of follow-up in 682 persons (mean age 58 +/- 10 years). Brain segmentation was used to quantify total, deep, and periventricular white matter lesion (WML) volume, and total brain, cortical gray matter and ventricular volume (%ICV). Lacunar infarcts were rated visually. Regression analyses were used to examine the prospective associations between serum ACE and brain measures. Patients with the highest serum ACE levels (>43.3 U/L) had borderline significantly more progression of deep WML volumes than patients with the lowest ACE levels (<21.8 U/L); mean difference (95% CI) in change was 0.20 (-0.02; 0.43) %ICV. On the contrary, patients with the highest serum ACE levels had significantly less progression of cortical brain atrophy than patients with the lowest ACE levels; mean difference (95% CI) in change was 0.78 (0.21; 1.36) %ICV. Serum ACE was not associated with subcortical atrophy, periventricular WML, or lacunar infarcts. Our results show that higher ACE activity is associated with somewhat more progression of deep WML volume, but with less progression of cortical brain atrophy. This suggests both detrimental and beneficial effects of high ACE levels on the brain.","Aged;Atrophy/blood/enzymology/pathology;Biomarkers/blood;Brain/*enzymology/*pathology;Cerebral Infarction/blood/enzymology/pathology;Cohort Studies;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*enzymology/*pathology;Neurodegenerative Diseases/blood/enzymology/pathology;Peptidyl-Dipeptidase A/*blood;Prospective Studies","Jochemsen, H. M.;Geerlings, M. I.;Grool, A. M.;Vincken, K. L.;Mali, W. P.;van der Graaf, Y.;Muller, M.",2012,,10.3233/jad-2012-111772,0,
3569,Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer's disease,"A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.",Alzheimer disease;article;association;brain atrophy;brain blood flow;brain perfusion;clinical feature;cognition;computer assisted tomography;human;major clinical study;parietal lobe;pathology;photon emission tomography;priority journal;temporal lobe,"Jobst, K. A.;Smith, A. D.;Barker, C. S.;Wear, A.;King, E. M.;Smith, A.;Anslow, P. A.;Molyneux, A. J.;Shepstone, B. J.;Soper, N.;Holmes, K. A.;Robinson, J. R.;Hope, R. A.;Oppenheimer, C.;Brockbank, K.;McDonald, B.",1992,,,0,
3570,Automated Multi-Atlas Labeling of the Fornix and Its Integrity in Alzheimer's Disease,"Alzheimer's disease is the most common form of dementia. Diffusion imaging provides information on white matter integrity not available with standard MRI, revealing additional information on how Alzheimer's disease affects the brain. Here we implemented and tested a multi-atlas labeling algorithm to segment the fornix and a point-correspondence tract matching scheme to assess fiber integrity in the fornix in diffusion MRI from 210 participants scanned as part of the Alzheimer's Disease Neuroimaging Initiative. Various diffusion-derived measures were used to relate fornix degeneration to cognitive decline. On 3D parametric tract models, mean diffusivity (MD) was more sen-sitive to group differences than fractional anisotropy (FA). Compared to previous studies, we mapped diffusion information along the fornix, yielding 3-D maps of degenerative changes along the tract in people with different stages of Alzheimer's disease.",,"Jin, Y.;Shi, Y.;Zhan, L.;Thompson, P. M.",2015,Apr,10.1109/isbi.2015.7163835,0,
3571,3D tract-specific local and global analysis of white matter integrity in Alzheimer's disease,"Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive decline in memory and other aspects of cognitive function. Diffusion-weighted imaging (DWI) offers a non-invasive approach to delineate the effects of AD on white matter (WM) integrity. Previous studies calculated either some summary statistics over regions of interest (ROI analysis) or some statistics along mean skeleton lines (Tract Based Spatial Statistic [TBSS]), so they cannot quantify subtle local WM alterations along major tracts. Here, a comprehensive WM analysis framework to map disease effects on 3D tracts both locally and globally, based on a study of 200 subjects: 49 healthy elderly normal controls, 110 with mild cognitive impairment, and 41 AD patients has been presented. 18 major WM tracts were extracted with our automated clustering algorithm-autoMATE (automated Multi-Atlas Tract Extraction); we then extracted multiple DWI-derived parameters of WM integrity along the WM tracts across all subjects. A novel statistical functional analysis method-FADTTS (Functional Analysis for Diffusion Tensor Tract Statistics) was applied to quantify degenerative patterns along WM tracts across different stages of AD. Gradually increasing WM alterations were found in all tracts in successive stages of AD. Among all 18 WM tracts, the fornix was most adversely affected. Among all the parameters, mean diffusivity (MD) was the most sensitive to WM alterations in AD. This study provides a systematic workflow to examine WM integrity across automatically computed 3D tracts in AD and may be useful in studying other neurological and psychiatric disorders. Hum Brain Mapp 38:1191-1207, 2017. (c) 2016 Wiley Periodicals, Inc.",Alzheimer's disease;diffusion-weighted MRI;functional statistical analysis;tract-specific analysis;white matter,"Jin, Y.;Huang, C.;Daianu, M.;Zhan, L.;Dennis, E. L.;Reid, R. I.;Jack, C. R., Jr.;Zhu, H.;Thompson, P. M.;Alzheimer's Disease Neuroimaging, Initiative",2017,Mar,,0,
3572,Reduced Cardiovascular Functions in Patients with Alzheimer's Disease,"Previous studies have suggested that cardiovascular functions might play a critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship among heart function, blood flow of cerebral vessels, and AD remains unclear. In the present study, AD patients (n = 34) and age- and gender-matched cognitively normal controls (n = 34) were recruited. Demographic and comorbidity information was collected. The ejection fraction was measured using echocardiography, and the mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar artery (BA), left terminal internal carotid artery (LTICA), and right terminal internal carotid artery (RTICA) were measured using transcranial Doppler. The data of lacunae, white matter changes, and plaques in the aortic arch and carotid arteries were collected from brain magnetic resonance imaging and computed tomography angiography images. Compared with normal controls, AD patients had lower ejection fractions and cerebral blood flow velocities and higher RI and PI in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid arteries. In the multivariate logistic regression analysis, the ejection fraction and the mean velocity of the BA and LTICA were independently associated with AD after adjusting for age, gender, education, vascular risk factors, arterial plaques, and brain ischemic lesions detected in the brain images. These findings suggest that heart function and vascular condition may play important roles in AD pathogenesis. Improving cardiovascular functions could be a promising approach for the prevention and treatment of AD.",Alzheimer's disease;cerebral blood flow;ejection fractions;heart,"Jin, W. S.;Bu, X. L.;Wang, Y. R.;Li, L.;Li, W. W.;Liu, Y. H.;Zhu, C.;Yao, X. Q.;Chen, Y.;Gao, C. Y.;Zhang, T.;Zhou, H. D.;Zeng, F.;Wang, Y. J.",2017,,,0,
3573,"Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment","Subcortical vascular cognitive impairment (sVCI) is caused by lacunar infarcts or extensive and/or diffuse lesions in the white matter that may disrupt the white matter circuitry connecting cortical and subcortical regions and result in the degeneration of neurons in these regions. This study used structural magnetic resonance imaging (MRI) and high angular resolution diffusion imaging (HARDI) techniques to examine cortical thickness, subcortical shapes, and white matter integrity in mild vascular cognitive impairment no dementia (VCIND Mild) and moderate-to-severe VCI (MSVCI). Our study found that compared to controls (n = 25), VCIND Mild (n = 25), and MSVCI (n = 30) showed thinner cortex predominantly in the frontal cortex. The cortex in MSVCI was thinner in the parietal and lateral temporal cortices than that in VCIND Mild. Moreover, compared to controls, VCIND Mild and MSVCI showed smaller shapes (i.e., volume reduction) in the thalamus, putamen, and globus pallidus and ventricular enlargement. Finally, compared to controls, VCIND Mild, and MSVCI showed an increased mean diffusivity in the white matter, while decreased generalized fractional anisotropy was only found in the MSVCI subjects. The major axonal bundles involved in the white matter abnormalities were mainly toward the frontal regions, including the internal capsule/corona radiata, uncinate fasciculus, and anterior section of the inferior fronto-occipital fasciculus, and were anatomically connected to the affected cortical and subcortical structures. Our findings suggest that abnormalities in cortical, subcortical, and white matter morphology in sVCI occur in anatomically connected structures, and that abnormalities progress along a similar trajectory from the mild to moderate and severe conditions. © 2013 Wiley Periodicals, Inc.",,"Jin Thong, J. Y.;Du, J.;Ratnarajah, N.;Dong, Y.;Soon, H. W.;Saini, M.;Tan, M. Z.;Tuan Ta, A.;Chen, C.;Qiu, A.",2014,May,,0,
3574,Diffusion kurtosis imaging on evaluation of white matter fiber in patients with Alzheimer's disease,"Objective: To explore the value of diffusion kurtosis imaging (DKI) on evaluation of white matter fiber in patients with Alzheimer's disease (AD). Methods: Totally 19 patients with AD (AD group) and 17 age-matched normal controls (control group) underwent DKI. The diffusion tensor imaging (DTI) and DKI parameters of white matter fiber tracts (genu and splenium of the corpus callosum [GCC, SCC], bilateral anterior cingulum and bilateral posterior cingulum [ACG, PCG], bilateral superior longitudinal fasciculus [SLF] and inferior fronto-occipiatal fasciculus [IFOF]) were measured and their correlation with the scores of mini-mental state examination (MMSE) was evaluated. Results: Compared with control group, AD group showed significant differences of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK) in bilateral GCC and SCC, bilateral ACG and PCG, MK, RK and AK in bilateral SLF and IFOF. For the same AD patient, compared with the other side, the differences of FA, MK, AK and RK in right ACG, FA in right PCG, FA, RD, MK and RK in left SLF were significant. All DTI and DKI parameters had correlations with MMSE, but MK in GCC was the best (r=0.55, P<0.05). Conclusion: The DKI can be used to assess the severity of cognitive deficient sensitively and accurately.",Alzheimer disease;article;axial kurtosis;cingulum (brain);clinical article;controlled study;corpus callosum;diffusion kurtosis imaging;diffusion tensor imaging;fractional anisotropy;human;mean diffusivity;mean kurtosis;Mini Mental State Examination;nuclear magnetic resonance imaging;occipitofrontal fasciculus;parameters;radial diffusivity;radial kurtosis;superior longitudinal fasciculus;white matter,"Jin, R.;Fan, G. G.;Li, S. B.;Wang, S. S.;Chen, B. Y.;Lyu, G. W.",2015,,10.13929/j.1003-3289.2015.08.009,0,
3575,"Association between MTHFR gene polymorphisms, smoking, and the incidence of vascular dementia","This study investigated the relationship between N5,N10-methylene tetrahydrofolic acid reductase (MTHFR) polymorphisms, smoking, and vascular dementia (VD). Polymerase chain reaction-restriction fragment length polymorphism analysis was used to analyze the frequency of the C/T polymorphism at position 677 of the MTHFR gene in 304 VD patients and 300 control patients with nondementia cerebral infarction. The CC, CT, and TT genotype frequencies of the MTHFR gene were 43.42%, 32.57%, and 24.01%, respectively, in the VD group, and 50.67%, 32.00%, and 17.33%, respectively, in the control group. The T allele frequency was significantly higher in the VD group than in the control group (P < .05). Among patients who smoked, the relative risk of VD in patients with the TT genotype and T allele was higher than in the control group (P < .05). Therefore, the smoking group with the T allele has the highest risk of VD, and synergy appears to exist between the MTHFR gene polymorphisms and smoking in susceptibility to VD.","Aged;Dementia, Vascular/*epidemiology/genetics;Female;*Gene-Environment Interaction;Genetic Predisposition to Disease;Humans;Incidence;Male;Methylenetetrahydrofolate Reductase (NADPH2)/*genetics;Middle Aged;*Polymorphism, Genetic;Risk Factors;Smoking/*epidemiology;N10-methylene tetrahydrofolic acid reductase (MTHFR);N5;correlation analysis;gene polymorphism;smoking;vascular dementia","Jin, P.;Hou, S.;Ding, B.;Li, D.;Liu, L.;Li, H.;Li, L.;Zhao, G.;Shao, Z.;Liu, X.",2013,Jul,10.1177/1010539513492819,0,
3576,[A study of subcortical infarcts and leukoencephalopathy (CADASIL) in a family with autosomal cerebral dominant arteriopathy],"OBJECTIVE: To investigate the clinical features, hereditary pattern, neuroimaging characteristics and diagnostic method of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: A systematic study on the clinical manifestations, neuroimaging characteristics, pathology and molecular genetics was performed. An investigation on the onset and hereditary pattern of the family tree of the proband was also done. RESULTS: The main clinical features of the proband including history of recurrent ischemic stroke, poor memory/cognition or dementia were noted. Fifteen cases pertaining to 4 generations of the proband with clinical or subclinical onset and confirmed classical family history of autosomal dominant hereditary were studied. Neuroimaging examination showed subcortical multiinfarct lesions and leukoencephalopathy. Electron microscope examination of the skin. Biopsy indicated thickening of basement membrane and presence of granular osmiophilic material (GOM) in the arterioles. A mutation on the fourth exon of notch 3 gene was revealed. Migraine, hypertension, diabetes and risk factors of arteriosclerosis were not found. All the features mentioned above in this family are in conformity with the diagnostic standard of CADASIL. CONCLUSIONS: It is possible to define CADASIL clinically by way of studying the clinical features, hereditary pattern, neuroimaging characteristics, skin biopsy and sequencing of gene without resorting to brain biopsy.","CADASIL/*diagnosis/*genetics/pathology;Diagnosis, Differential;Exons/genetics;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Pedigree;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface/genetics;Skin/pathology","Jin, D. X.;Chen, X. Y.;Zhang, X.",2004,Dec,,0,
3577,The cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"OBJECTIVE: To investigate the cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: The blood flow velocity of cerebral arteries was measured by using transcranial Doppler ultrasound (TCD) in 6 cases with CADASIL and a quite number of age and sex matched control subjects. All patients (4 were symptomatic and 2 asymptomatic), being an established CADASIL family with the diagnosis confirmed by clinical characteristics, neuroimaging, pathology and molecular genetics, had abnormal mark signals on MR imagining and no history of hypertension, diabetes, heart disease and migraine. A routinely TCD detection, including peak-systolic velocity (Vp), end-diastolic velocity (Vd), mean velocity (Vm) and pulsatility index (PI), was carried out on the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA) and vertebral arteries (VA) as well as the basilar artery (BA). A comparison between the cases and controls was made. Then, the changes of flow velocity in middle cerebral arteries (MCA) of the patients with CADASIL were observed before and after breathholding tests. In addition, brain CT perfusion imaging (CTP) was carried out in all the cases by using 16-slice spiral CT. RESULTS: The appearances of frequency spectrum were nearly normal in all the cases and there was no abnormality between the two sides on velocity (P > 0.05). As compared with the controls, the bilateral Vp, Vd and Vm in ACA and PCA were decreased obviously (P < 0.05). The velocity parameters of MCA with the exception of left Vm and right PI showed changes (P < 0.05) and there were no changes of PI in the bilateral ACA, PCA and Left MCA (P > 0.05). Moreover, there were marked changes in MCA (including Vm, Vd and PI) of all the cases as compared with the controls after breathholding (P < 0.01). Brain perfusion imaging showing the regional cerebral blood flow and regional cerebral blood volume in frontal lobes were obviously decreasing (P < 0.01) and there was no significant variation of mean transit time (MTT). CONCLUSIONS: The characteristic hemodynamic changes in our group is the decreasing flow velocity in bilateral ACA, PCA and MCA and the dominating low flow area occurring usually in frontal and temporal lobes. These changes are in conformity with the ischemic area shown in pathology and neuroimaging in CADASIL patients.",Adult;Blood Flow Velocity;CADASIL/ physiopathology/ultrasonography;Cerebrovascular Circulation;Female;Humans;Male;Middle Aged,"Jin, D. X.;Chen, X. Y.;Huang, H.;Zhang, X.",2006,Dec,,0,
3578,Characterization of spheroids in hereditary diffuse leukoencephalopathy with axonal spheroids,"Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a neurodegenerative disease clinically characterized by slowly progressive cognitive decline and motor dysfunction. Neuropathology shows diffuse degeneration in the white matter, with prominent presence of widespread axonal spheroids. To investigate the mechanism underlying HDLS neurodegeneration, we characterized spheroids and examined their development in the degenerated white matter. Analysis revealed that the spheroids are an early neuropathological manifestation in the white matter degeneration and involve axonal component proteins and α-synuclein. The development of spheroids facilitates in initiating neurodegeneration in HDLS.",alpha synuclein;adult;amino acid substitution;article;autopsy;axonal spheroid;brain atrophy;brain region;brain tissue;case report;cognition;cognitive defect;degenerative disease;dementia;DNA sequence;gait disorder;genetic variability;hereditary diffuse leukoencephalopathy with axonal spheroid;heterozygote;human;human tissue;immunohistochemistry;investigative procedures;leukoencephalopathy;male;middle aged;motor dysfunction;nerve degeneration;neuroimaging;nuclear magnetic resonance imaging;parkinsonism;priority journal;pyramidal sign,"Jin, C.;Washimi, Y.;Yoshida, K.;Hashizume, Y.;Yazawa, I.",2015,,,0,
3579,(11)C-PIB retention patterns in white and grey cerebral matter in idiopathic normal pressure hydrocephalus patients. A visual analysis Patrones de retencion de (11)C-PIB en la sustancia blanca y en la sustancia gris cerebral de pacientes con hidrocefalia a presion normal idiopatica. Un analisis visual,"OBJECTIVE: Cortical cerebral amyloid disease, a hallmark of Alzheimer's disease, has also been observed in idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to compare the (11)C-PIB PET/CT retention pattern in iNPH patients and healthy subjects. MATERIAL AND METHODS: A comparison was made of the (11)C-PIB PET/CT retention pattern in 13 iNPH patients selected for surgical deviation, compared to a normal control population. Images were visually analyzed and scored for gray matter and white matter (WM) from 1 to 4 (slight to very high PIB retention). The scoring was analyzed in both groups separately for infra- and supra-tentorial regions. A comprehensive clinical report was presented in terms of positive, negative, or equivocal. RESULTS: (11)C-PIB PET/CT scan were reported as negative in 8, positive in 3, and equivocal in 2. Five of 13 patients showed at least one cortical area with PIB retention with an intensity higher than that observed in the control group. Overall, white matter (WM) PIB retention of iNPH scored lower than in the control group, showing a statistically significant difference in the infratentorial WM (92/104 vs 54/56; p<.05) and a tendency to be lower in the supratentorial regions (70/84 vs 122/156, p=.327), in particular in the upper periventricular region (25/28 vs 40/52; p=.134). CONCLUSIONS: The PIB retention pattern seems to be different in NPH, compared to normal subjects. PIB retention in WM of NPH appears less intense than in healthy subjects, and they show a higher degree of PIB retention in cortical regions. This deserves to be taken it into account.",(11)c-pib;(11)c-pib-pet;Amyloid PET;Hidrocefalia a presion normal;Normal pressure hydrocephalus;PET amiloide;Pet/ct;Pet/tc;Sustancia blanca;White matter,"Jimenez-Bonilla, J. F.;Quirce, R.;de Arcocha-Torres, M.;Martinez-Rodriguez, I.;Martinez-Amador, N.;Sanchez-Juan, P.;Pozueta, A.;Martin-Laez, R.;Banzo, I.;Rodriguez-Rodriguez, E.",2017,Aug 30,,0,
3580,Prevalence of hippocampal enlarged perivascular spaces in a sample of patients with hypertension and their relation with vascular risk factors and cognitive function,"OBJECTIVES: The clinical importance of hippocampal enlarged perivascular spaces (H-EPVS) remains uncertain. We aimed to study their association with vascular risk factors, cognitive function and mild cognitive impairment (MCI). METHODS: Data were obtained from the ISSYS (Investigating Silent Strokes in hYpertensives, a magnetic resonance imaging Study) cohort, which is a prospective study of patients with hypertension aged 50-70 with no prior stroke or dementia. Participants were clinically evaluated and underwent a cognitive screening test, Dementia Rating Scale-2, which includes five cognitive subscales (attention, initiation/perseveration, conceptualisation, construction and memory). Besides, they were diagnosed with MCI or normal ageing following standard criteria. H-EPVS were manually counted on brain MRI according to a previous scale and defined as extensive when H-EPVS count was >/=7 (upper quartile). Multivariate models were created to study the relationship between H-EPVS, vascular risk factors and cognitive function. RESULTS: 723 patients were included; the median age was 64 (59-67) and 51% were male. Seventy-two patients (10%) were diagnosed with MCI and 612 (84.6%) had at least 1 H-EPVS. Older age (OR per year=1.04, 95% CI 1.01 to 1.08) and poor blood pressure treatment compliance (OR=1.50, 95% CI 1.07 to 2.11) were independently associated with extensive H-EPVS. Regarding cognitive function, H-EPVS were independently and inversely correlated with verbal reasoning (beta=-0.021, 95% CI -0.038 to -0.003). No association was found between H-EPVS and MCI. CONCLUSIONS: H-EPVS are a frequent finding in patients with hypertension and are associated with ageing and poor hypertension treatment compliance. Besides, H-EPVS are associated with worse verbal reasoning function.",cerebral small vessel disease;cognitive function;enlarged perivascular spaces;hypertension;mild cognitive impairment,"Jimenez-Balado, J.;Riba-Llena, I.;Garde, E.;Valor, M.;Gutierrez, B.;Pujadas, F.;Delgado, P.",2018,Jan 11,,0,
3581,Bilateral Paramedian Thalamic Artery Infarcts: Report of 10 Cases,"The paramedian thalamic arteries can arise as a pair from each P1 of the posterior cerebral artery, but they may also arise equally from a common trunk off one P1, thus supplying thalamus bilaterally. Such a common trunk is called the artery of Percheron and supplies the mesial aspects of both thalami and the rostral midbrain. This is a retrospective review of 1253 consecutive patients with ischemic stroke enrolled in a stroke registry within an 8-year period (January 2001-December 2008). All were evaluated with detailed clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), blood studies, electrocardiogram, and transthoracic echocardiography. All standard risk factors were recorded in these patients. Ten patients (0.7%) in this series presented with a first-ever thalamic stroke demonstrating bilateral paramedian thalamic lesions on MRI. The main cause of bilateral paramedian thalamic infarctions was small artery disease (60%), followed by cardioembolism (40%). A well-defined clinical picture is shown in bilateral paramedian thalamic artery infarcts. These patients had disorder's consisting of consciousness, memory dysfunctions, various types of vertical gaze paresis, and psychological changes. Although neurologic deficits and hypersomnia recovered to large extent in patients with paramedian thalamic infarcts, cognitive deficits that were mainly linked with bilateral and left-sided lesions often persisted. Vertical gaze paresis tended to improve and never seriously disturbed the patient's activities. We believe that these kinds of strokes have been commonly overlooked, especially without widespread use of MRI. © 2010 National Stroke Association.",,"Jiménez Caballero, P. E.",2010,July,,0,
3582,Segmentation and volumetric analysis of the caudate nucleus in Alzheimer's disease,"OBJECTIVES: A quantitative volumetric analysis of caudate nucleus can provide valuable information in early diagnosis and prognosis of patients with Alzheimer's diseases (AD). Purpose of the study is to estimate the volume of segmented caudate nucleus from MR images and to correlate the variation in the segmented volume with respect to the total brain volume. We have also tried to evaluate the caudate nucleus atrophy with the age related atrophy of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) in a group of Alzheimer's disease patients. METHODS: 3D fast low angle shot (3D FLASH) brain MR images of 15 AD patients, 15 normal volunteers and 15 patients who had normally diagnosed MR images were included in the study. Brain tissue and caudate nuclei were segmented using the statistical parametric mapping package and a semi-automatic tool, respectively and the volumes were estimated. Volume of segmented caudate nucleus is correlated with respect to the total brain volume. Further, the caudate nucleus atrophy is estimated with the age related atrophy of WM, GM and CSF in a group of AD patients. RESULTS: Significant reduction in the caudate volume of AD patients was observed compared to that of the normal volunteers. Statistical analysis also showed significant variation in the volume of GM and CSF of AD patients. Among the patients who had normal appearing brain, 33% showed significant changes in the caudate volume. We hypothesize that these changes can be considered as an indication of early AD. CONCLUSION: The method of volumetric analysis of brain structures is simple and effective way of early diagnosis of neurological disorders like Alzheimer's disease. We have illustrated this with the observed changes in the volume of caudate nucleus in a group of patients. A detailed study with more subjects will be useful in correlating these results for early diagnosis of AD.","Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/ pathology;Caudate Nucleus/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Observer Variation;Organ Size;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity","Jiji, S.;Smitha, K. A.;Gupta, A. K.;Pillai, V. P.;Jayasree, R. S.",2013,Sep,10.1016/j.ejrad.2013.03.012,0,
3583,An inverse relationship between serum macrophage inhibitory cytokine-1 levels and brain white matter integrity in community-dwelling older individuals,"Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a marker of inflammation that has been associated with atherosclerosis. We have previously demonstrated its relationships with cognitive decline and cerebral gray matter volumes, suggesting its role as a biomarker of cognitive impairment. Considering that it is widely distributed in the brain, and both inflammation and vascular pathology impact on white matter (WM) integrity, we examined the relationship between MIC-1/GDF15 and measures of WM integrity, including WM volumes, mean fractional anisotropy (FA) values and WM hyperintensity (WMH) volumes in a community-dwelling non-demented sample of older individuals (n=327, 70-90 years old). We found that the mean FA values were negatively associated with MIC-1/GDF15 serum levels, after Bonferroni correction. The voxel-wise analysis showed negative relationships between MIC-1/GDF15 serum levels and FA values in corticospinal tract, corpus callosum (including genu, body and splenium parts), superior longitudinal fasciculus, cingulum, as well as anterior and posterior thalamic radiation. Whole brain WMH volumes, especially deep WMH volumes, showed a non-significant trend for a positive association with MIC-1/GDF15 serum levels. The associations between MIC-1/GDF15 serum levels and WM integrity showed a non-significant trend of being stronger for the individuals classified as mild cognitive impairment, compared to the normal ageing participants. The findings suggest that high serum MIC-1/GDF15 levels indicate reduced WM integrity and possibly greater WM pathology.",,"Jiang, J.;Trollor, J. N.;Brown, D. A.;Crawford, J. D.;Thalamuthu, A.;Smith, E.;Breit, S. N.;Liu, T.;Brodaty, H.;Baune, B. T.;Sachdev, P. S.;Wen, W.",2015,Dec,10.1016/j.psyneuen.2015.07.610,0,
3584,Changes of head magnetic resonance imaging and transcranial Doppler in patients with post-stroke cognitive impairment,"Objective: To investigate the changes of head magnetic resonance imaging (MRI) and transcranial Doppler (TCD) in patients with vascular cognitive impairment but no dementia (VCIND) and their relationship with cognitive impairment. Methods: The head MRI and TCD in 52 patients with post-stroke VCIND were studied retrospectively, and were compared to the findings of head MRI and TCD of 40 stroke patients without cognitive impairment and 42 healthy controls. The Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT) were used to assess the mental status. Results: Circled digit oneNot only the proportion (46.2%) of the lesions of frontal and temporal lobe in the VCIND group was higher than that (22.5%) in the stroke group (χ(2) = 5.50, P < 0.05), but also the proportion (63.5%) in patients with multiple infarcts was higher than that (40%) in the stroke group (χ(2) = 5.00, P < 0.05). The cognitive decline in the patients whose foci located in the frontal and temporal lobes (MMSE = 20.6 ± 1.3, CDT = 1.8 ± 1.0) in the VCIND group compared to those in the other parts (MMSE = 24.2 ± 1.3, and CDT = 2.4 ± 0.7, all P < 0.05); and the patients with multiple foci (MMSE = 21.7 ± 1.6, and CDT = 2.0 ± 1.0) compared to those with single focus (MMSE = 23.8 ± 1.1, CDT = 2.4 ± 1.0) (P < 0.05 and P > 0.05). Circled digit twoAs compared to the normal controls group (26.2%) and the stroke group (62.5%), the incidence of abnormal hemodynamics (90.4%) was higher in the VCIND group (χ(2) = 40.63, P < 0.05). Circled digit threeThe mean flow velocities of the anterior and middle cerebral arteries in the VCIND and stroke groups were lower than those in the control group. The mean flow velocities of the anterior and middle cerebral arteries were decreased in the VCIND group compared to the stroke group, and there were significant differences between them (P < 0.05). Conclusion: Circled digit oneThe lesions of frontal and temporal lobe and the numbers of lesions are the important factors affecting VCIND. Circled digit twoThe VCIND group had obvious abnormal hemodynamics and cerebral circulation insufficiency. The insufficiency of the internal carotid artery may be associated with the impaired cognitive function after stroke.",,"Jiang, B.;Meng, X. L.;Shu, G. M.;Yao, C. S.;Cai, X.;Guo, Y. Q.",2009,July,,0,
3585,(18)F-FDDNP positron emission tomography in differentiating Alzheimer disease and vascular dementia,"Background: At present, some neurological imaging methods, including MRI, fMRI, 2-(1-(6-[(2-[(18)F]fluoroethyl)(methyl) amino]-2-naphthyl) ethylidene) malononitrile ((18)F-FDDNP) positron emission tomography (PET), are. helpful but not specific for the diagnosis of Alzheimer disease (AD). (18)F-FDG is a special marker of beta-amyloid (Aβ), thus AD can be diagnosed by (18)F-FDDNP PET at early period. Objective: To evaluate the role of 18F-FDDNP PET in the diagnosis of AD, and establish reliable clinical biological indexes for the diagnosis of AD patients. Design: A controlled analysis. Settings: Department of Geriatric Neurology and Department of Nuclear Medicine, the General Hospital of Chinese PLA. Participants: Patients visiting the General Hospital of Chinese PLA from May 2004 to March 2005 were selected. Informed consents were obtained from all the participants. 1 AD group (n =7): (74.88±12.03) years old; Accorded with the criteria related to diagnosis of",,"Jia, J. J.;Guo, Z.;Tang, H. C.;Zhang, J. M.;Wang, L. N.;Wang, Z. F.;Sun, B. B.;Tian, J. H.",2007,3,,0,
3586,"The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial","INTRODUCTION: Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large-scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl-3-n-butylphthalide (NBP) is effective for cognitive impairment of vascular origin. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 50-70 years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating >/=0.5 on at least one domain and global score </=0.5; a mini-mental state examination score >/=20 (primary school) or >/=24 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned to NBP 200 mg three times daily or matched placebo (1:1) for 24 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population. RESULTS: This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS-cog (NBP change -2.46 vs. placebo -1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P = .01; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms. DISCUSSION: Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.",,"Jia, J.;Wei, C.;Liang, J.;Zhou, A.;Zuo, X.;Song, H.;Wu, L.;Chen, X.;Chen, S.;Zhang, J.;Wu, J.;Wang, K.;Chu, L.;Peng, D.;Lv, P.;Guo, H.;Niu, X.;Chen, Y.;Dong, W.;Han, X.;Fang, B.;Peng, M.;Li, D.;Jia, Q.;Huang, L.",2016,Feb,10.1016/j.jalz.2015.04.010,0,
3587,Distinct white matter microstructural abnormalities and extracellular water increases relate to cognitive impairment in Alzheimer's disease with and without cerebrovascular disease,"BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown. To cover these gaps, we aimed to characterize the WM free water and tissue microstructural changes in AD and mixed dementia as well as their associations with cognition using a novel free water imaging method. METHODS: We compared WM free water and free water-corrected DTI measures as well as white matter hyperintensity (WMH) in patients with AD with and without cerebrovascular disease, patients with vascular dementia, and age-matched healthy control subjects. RESULTS: The cerebrovascular disease groups had higher free water than the non-cerebrovascular disease groups. Importantly, besides the cerebrovascular disease groups, patients with AD without cerebrovascular disease also had increased free water in normal-appearing WM compared with healthy control subjects, reflecting mild vascular damage. Such free water increases in WM or normal-appearing WM (but not WMH) contributed to dementia severity. Whole-brain voxel-wise analysis revealed a close association between widespread free water increases and poorer attention, executive functioning, visual construction, and motor performance, whereas only left hemispheric free water increases were related to language deficits. Moreover, compared with the original DTI metrics, the free water-corrected DTI metric revealed tissue damage-specific (frontal and occipital) microstructural differences between the cerebrovascular disease and non-cerebrovascular disease groups. In contrast to both lobar and subcortical/brainstem free water increases, only focal lobar microstructural damage was associated with poorer cognitive performance. CONCLUSIONS: Our findings suggest that free water analysis isolates probable mild vascular damage from WM microstructural alterations and underscore the importance of normal-appearing WM changes underlying cognitive and functional impairment in AD with and without cerebrovascular disease. Further developed, the combined free water and tissue neuroimaging assays could help in differential diagnosis, treatment planning, and disease monitoring of patients with mixed dementia.",Alzheimer's disease;Cerebrovascular disease;Cognitive impairment;Diffusion tensor imaging;Extracellular water;Free water imaging;Vascular damage,"Ji, F.;Pasternak, O.;Liu, S.;Loke, Y. M.;Choo, B. L.;Hilal, S.;Xu, X.;Ikram, M. K.;Venketasubramanian, N.;Chen, C. L.;Zhou, J.",2017,Aug 17,,0,
3588,Some observations on the spectrum of dementia,"A study was designed to generate epidemiological and clinical data on dementia, in a teaching hospital in India. It was conducted on 124 (94 male and 30 female) elderly patients (aged more than 60 years) presenting with clinical syndrome of dementia (DSM-3). Their age range was 64-78 (mean 65.7 ± 4.1) years. Detailed clinical, biochemical, radiological and electrophysiological evaluation was done to establish etiology. Patients with psychiatric ailments, cranial trauma and tumors were excluded. The study period was 4.2 years. Multi-infarct dementia (MID) was observed to be commonest cause of dementia and was present in 59 (47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB) and neurocysticercosis (NCC). Alcohol-related dementia was present in 13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in 9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria) in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob Disease. We conclude that AD, which is irreversible and common in the west, is relatively uncommon in India as compared to MID, infections and malnutrition, which are potentially treatable.",alcohol;adult;aged;alcohol consumption;Alzheimer disease;article;clinical feature;cognitive defect;computer assisted tomography;controlled study;Creutzfeldt Jakob disease;cyanocobalamin deficiency;dementia;diabetes mellitus;disease association;electroencephalography;electromyography;female;human;Huntington chorea;hydrocephalus;hyperthyroidism;hypothyroidism;India;major clinical study;male;malnutrition;memory disorder;multiinfarct dementia;myxedema;nerve conduction;neurocysticercosis;nuclear magnetic resonance imaging;Parkinson disease;population research;risk factor;thyrotoxicosis;tuberculosis,"Jha, S.;Patel, R.",2004,,,0,
3589,Clinical factors related to brain structure in HIV: the CHARTER study,"Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n = 251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression.","AIDS Dementia Complex/ blood/ cerebrospinal fluid/etiology/pathology/virology;Adult;Aged;Anti-Retroviral Agents/administration & dosage;Antiretroviral Therapy, Highly Active;CD4 Lymphocyte Count;CD4-Positive T-Lymphocytes/pathology/virology;Cerebral Cortex/pathology/virology;Female;HIV/physiology;HIV Infections/ blood/ cerebrospinal fluid/complications/drug;therapy/pathology/virology;Hepacivirus/physiology;Hepatitis C/ blood/ cerebrospinal fluid/complications/virology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;RNA, Viral/blood/cerebrospinal fluid;Viral Load","Jernigan, T. L.;Archibald, S. L.;Fennema-Notestine, C.;Taylor, M. J.;Theilmann, R. J.;Julaton, M. D.;Notestine, R. J.;Wolfson, T.;Letendre, S. L.;Ellis, R. J.;Heaton, R. K.;Gamst, A. C.;Franklin, D. R., Jr.;Clifford, D. B.;Collier, A. C.;Gelman, B. B.;Marra, C.;McArthur, J. C.;McCutchan, J. A.;Morgello, S.;Simpson, D. M.;Grant, I.",2011,Jun,10.1007/s13365-011-0032-7,0,
3590,Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group,"Magnetic resonance imaging was used to compare male subjects seropositive for antibody to human immunodeficiency virus type 1 (HIV positive), with and without medical symptoms, with two groups of men who were seronegative (HIV negative). The control subjects included men at high risk for exposure to HIV-1 and those at low risk. None of the HIV-positive subjects met criteria for HIV-associated dementia or had detectable opportunistic brain disease. Quantitative image-analytic techniques were used to estimate volumes of ventricular and cortical cerebrospinal fluid, cerebral white matter, and cortical and subcortical gray matter structures. Relative to low-risk group control subjects and asymptomatic HIV-positive subjects, nondemented but medically symptomatic HIV-positive subjects showed significant increases in cerebrospinal fluid, reduced volume of cerebral white matter, and reduced cerebral gray matter volumes. Unexpectedly, however, some cerebrospinal fluid increases and gray matter volume decreases were present in the seronegative high-risk control subjects as well.",Adult;Brain/ pathology;Brain Chemistry;HIV Infections/cerebrospinal fluid/ pathology;HIV Seropositivity/cerebrospinal fluid/pathology;Humans;Magnetic Resonance Imaging;Male,"Jernigan, T. L.;Archibald, S.;Hesselink, J. R.;Atkinson, J. H.;Velin, R. A.;McCutchan, J. A.;Chandler, J.;Grant, I.",1993,Mar,,0,
3591,"Cerebral structure on MRI, Part II: Specific changes in Alzheimer's and Huntington's Diseases","Using magnetic resonance (MR) imaging and morphometric techniques, groups of patients with Alzheimer's disease (AD) and Huntington's disease (HD) were compared with a large group of normal control subjects. Measures of volume loss in specific subcortical nuclei and eight cortical regions as well as an index of white matter abnormality were obtained. Results indicated expected widespread cortical volume reductions in AD, which were especially severe in mesial cortices; but comparable reductions were present in subcortical structures, particularly the thalamus. In HD, the greatest reductions were in striatal structures, but significant abnormalities were also detected in the thalamus and inferior cortical areas, especially in mesial temporal lobe structures. Significant degeneration in white matter was present in both groups, but was more dramatic in the HD patients. The significant diencephalic reduction in AD may make an important contribution to early memory deficits in the disorder, which are usually attributed to hippocampal damage, Similarly, damage to both the thalamus and mesial temporal lobe structures may play a role in the memory deficits of HD.",,"Jernigan, T. J.;Salmon, D. P.;Butters, N.;Hesselink, J. R.",1991,1991,,0,
3592,Prevalence and severity of microbleeds in a memory clinic setting,,"Aged;Aged, 80 and over;Alzheimer Disease/epidemiology;Apolipoproteins E/genetics;Cerebral Hemorrhage/diagnosis/*epidemiology;Cognition Disorders/epidemiology;Cohort Studies;Comorbidity;Dementia/epidemiology;Dementia, Vascular/epidemiology;Female;Humans;Hypertension/epidemiology;Israel;Leadership;Magnetic Resonance Imaging;Male;Memory Disorders/*epidemiology/etiology;Mental Disorders/epidemiology;Middle Aged;Nervous System Diseases/epidemiology;Netherlands/epidemiology;Prevalence;Prospective Studies;Psychological Tests;Severity of Illness Index","Jeret, J. S.",2007,Jan 30,10.1212/01.wnl.0000255961.93980.1c,0,
3593,Assessment of change in glucose metabolism in white matter of amyloid-positive patients with Alzheimer disease using F-18 FDG PET,"In Alzheimer disease (AD), neuroinflammation is an important process related to the deposition of beta-amyloid plaques and the activation of microglia. The inflammatory process can occur in both the gray matter and the white matter. We evaluated glucose metabolism of the white matter in AD patients and compared the value with cognitive parameters of the patients.Eighteen AD patients and 18 healthy subjects underwent F-18 fluorodeoxyglucose (FDG) and F-18 florbetaben positron emission tomography (PET). After segmentation of the white matter in both PET images, the specific binding ratio (SBR) of the global and regional cerebral white matter was checked. We evaluated the differences in SBR of the global and regional white matter between AD patients and healthy subjects. Then, we assessed the correlation between SBR and cognitive parameters in AD patients.In F-18 FDG PET images, the global white matter SBR was significantly higher in AD patients than in healthy subjects. In the regional analysis, the white matter SBR was significantly higher for the frontal, temporal, and parietal areas in AD patients. In the correlation analysis with F-18 FDG PET, SBR was significantly correlated with the Global Deterioration Scale, Mini-Mental State Examination scores, and amyloid deposition.Glucose metabolism of the white matter was significantly higher in AD patients than in healthy subjects and it was related to the scores of cognitive parameters. We suggest that F-18 FDG PET, like 18-kDa translocator protein PET, could be used as an indicator of neuroinflammation; however, further research is needed for a direct comparison between the 2 tests.","0 (4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene);0 (Amyloid);0 (Aniline Compounds);0 (Radiopharmaceuticals);0 (Stilbenes);0Z5B2CJX4D (Fluorodeoxyglucose F18);IY9XDZ35W2 (Glucose);Aged;Alzheimer Disease/diagnostic imaging/ metabolism/psychology;Amyloid/ metabolism;Aniline Compounds;Brain/diagnostic imaging/ metabolism;Cognition;Female;Fluorodeoxyglucose F18;Glucose/ metabolism;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Positron-Emission Tomography;Radiopharmaceuticals;Retrospective Studies;Stilbenes;White Matter/diagnostic imaging/ metabolism","Jeong, Y. J.;Yoon, H. J.;Kang, D. Y.",2017,Dec,,0,
3594,Hypertensive pontine microhemorrhage,"BACKGROUND AND PURPOSE: This study investigated whether the topography of hypertensive pontine microhemorrhages (hPMHs) resembles that of larger primary pontine hemorrhages. METHODS: Sixty-nine consecutive patients with small-vessel disease underwent imaging with gradient-echo MRI, and 27 patients with hPMH were detected. Lesion size and location along the rostrocaudal (longitudinal), lateral (coronal), and anteroposterior (sagittal) axes were determined. RESULTS: A total of 52 hPMHs were identified in the 27 patients (mean, 1.93+/-2.4 per patient). The lesions showed a nonrandom distribution, with a propensity to occur in the middle pons in the rostrocaudal axis, posterior half of the basis pontis in the anteroposterior axis, and central subdivision within the lateral axis. The area of hPMH ranged from 1.3 to 19.0 mm2 (mean, 5.06+/-3.72 mm2). The size of hPMH did not vary as a function of lesion location. CONCLUSIONS: Previous studies reported that primary pontine hemorrhages tend to occur in the middle pons and at the junction of basis pontis and tegmentum. Therefore, topographical correspondences between large and small pontine hemorrhages may provide evidence that the 2 lesions share some etiological basis. Further investigation may determine whether hPMHs portend future symptomatic primary pontine hemorrhages.","Aged;Aged, 80 and over;Cognition Disorders/diagnosis/etiology;Dementia, Vascular/complications/ diagnosis;Demography;Echo-Planar Imaging;Female;Humans;Hypertension/complications/ diagnosis;Intracranial Hemorrhages/classification/complications/ diagnosis;Magnetic Resonance Imaging;Male;Microcirculation/pathology;Middle Aged;Neuropsychological Tests;Pons/ blood supply/pathology;Prevalence;Risk Factors;Severity of Illness Index","Jeong, J. H.;Yoon, S. J.;Kang, S. J.;Choi, K. G.;Na, D. L.",2002,Apr,,0,
3595,"Age, hypertension, and genetic polymorphisms and their relative associations with white matter hyperintensities in Korean patients with Alzheimer’s disease","White matter hyperintensities are known to influence dementia in Alzheimer’s disease. Genetic components are suggested as putative risk factors for vascular pathology and cognitive decline. This study aimed to determine whether there is an association between candidate genetic polymorphisms and the severity of white matter hyperintensities in patients with Alzheimer’s disease. Methods: Seventy-five patients diagnosed with Alzheimer’s disease underwent genetic tests for specific alleles of apolipoprotein E, angiotensin-converting enzyme, and methylenetetrahydrofolate reductase. All patients underwent brain magnetic resonance imaging scans and neuropsychological tests. The severity of white matter hyperintensities was semiquantified using the CREDOS rating scale, and patients were divided into three groups according to their rating. Results:The severity of white matter hyperintensities was related to age and hypertension. However, none of the gene polymorphisms we tested was found to be associated with the severity of white matter hyperintensities. Conclusion:The genetic polymorphisms found in apolipoprotein E, angiotensin-converting enzyme and methylenetetrahydrofolate reductase did not contribute to white matter hyperintensities in Alzheimer’s disease.Only age and hypertension factors were found to be contributory to white matter hyperintensities.",,"Jeong, H.;Son, S.;Kim, S. K.;Park, K. J.;Choi, N. C.;Kwon, O. Y.;Lim, B.;Kang, H.",2015,2015,,0,
3596,MR imaging of the brain in patients with AIDS: value of routine use of i.v. gadopentetate dimeglumine,"OBJECTIVE: A prospective study was conducted to explore the value of routine administration of IV gadopentetate dimeglumine for MR imaging of the brain in patients with AIDS. SUBJECTS AND METHODS: Over a 19-month period, MR images of the brain in 51 consecutive AIDS patients were obtained routinely both with and without IV gadopentetate dimeglumine. Unenhanced and contrast-enhanced images from the resulting 63 studies were viewed together. Findings were classified into one or more of three categories: normal, mass or focal lesions, or white matter disease. The number of focal or mass lesions was recorded. Lesion conspicuity on the unenhanced and enhanced images was compared. Ventricular enlargement was also graded. Available medical records and laboratory data of the patients were reviewed. RESULTS: Of the 63 MR studies reviewed, 39 (62%) were abnormal. In no case was a normal unenhanced MR study rendered abnormal after the administration of gadopentetate dimeglumine. Overall, T2-weighted images showed twice as many focal or mass lesions than contrast-enhanced T1-weighted images did. Most lesions detected on the T2-weighted images did not show enhancement with contrast material. White matter disease was the most common abnormality detected. The group of patients with white matter disease also had the highest occurrence of ventriculomegaly. CONCLUSION: Our study does not support the routine use of gadopentetate dimeglumine for MR imaging of the brain in patients with AIDS. Our experience emphasizes the importance of a normal T2-weighted image.","AIDS Dementia Complex/diagnosis;AIDS-Related Opportunistic Infections/diagnosis;Acquired Immunodeficiency Syndrome/ complications;Adult;Brain/ pathology;Brain Diseases/complications/ diagnosis;Brain Neoplasms/complications/diagnosis;Contrast Media;Drug Combinations;Gadolinium DTPA;Humans;Injections, Intravenous;Magnetic Resonance Imaging;Male;Meglumine/administration & dosage;Middle Aged;Organometallic Compounds/administration & dosage;Pentetic Acid/administration & dosage","Jensen, M. C.;Brant-Zawadzki, M.",1993,Jan,10.2214/ajr.160.1.8416615,0,
3597,Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI,"In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity- matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.",adult;aged;article;brain ventricle;clinical article;cognition;controlled study;degenerative disease;depression;female;geriatric patient;human;Huntington chorea;learning;male;memory;nuclear magnetic resonance imaging;Parkinson disease;recall;recognition;semantics;white matter,"Jenkins, M.;Malloy, P.;Salloway, S.;Cohen, R.;Rogg, J.;Tung, G.;Kohn, R.;Westlake, R.;Johnson, E. G.;Richardson, E.",1998,,,0,
3598,Four-repeat tauopathy clinically presenting as posterior cortical atrophy: Atypical corticobasal degeneration?,"A man aged 55 with negative family history presented with progressive decline in spatial orientation and visual functions for 2 years. He showed impaired optic fixation, optic ataxia, agraphia, acalculia, ideomotor apraxia, disturbed right-left differentiation but preserved color matching, memory and motor perception, gradually progressing to dementia, without extrapyramidal signs. Brain MRI and PET showed severe bilateral atrophy and hypometabolism in parieto-occipital areas with sparing of visual perception area and frontal lobes. Treatment with cholinesterase inhibitors had no effect. Death occurred 61/2 years after onset of symptoms from bronchopneumonia. Clinical diagnosis was posterior cortical atrophy (Benson's syndrome). Autopsy showed severe bilateral parietal cortical atrophy, less severe in other brain regions without subcortical lesions. Histology revealed severe diffuse tauopathy with neuronal loss, neurofibrillary tangles, neuropil threads, and tau deposits in astroglia and oligodendroglia in parietal, temporal, occipital cortex, less in frontal cortex and hippocampus, putamen, claustrum, thalamus and subthalamus. Severely involved white matter showed many tau-positive threads, comma-like inclusions in oligodendroglia (coiled bodies) and in astroglia. Mild neuronal loss in substantia nigra was associated with massive tau pathology, also involving several brainstem nuclei, cerebellum being preserved. There were neither astrocytic plaques nor any amyloid pathology. Neuronal and glial inclusions were generally 4R-tau-positive and 3R-tau-negative. No TDP-43 and α-synuclein inclusions were detected. Spinal cord was not available. No mutations were found in the MAPT gene. This is the first published case with the fully developed clinical and neuroimaging picture of posterior cortical atrophy, morphologically presenting as a distinct phenotype of 4R-tauopathy that closely resembles (atypical) CBD. © 2010 Springer-Verlag.",cholinesterase inhibitor;adult;agraphia;apraxia;article;ataxia;Benson syndrome;brain cortex atrophy;brain metabolism;case report;cell inclusion;cognitive defect;corticobasal degeneration;dementia;histopathology;human;human tissue;male;neuropathology;nuclear magnetic resonance imaging;parieto-occipital sulcus;positron emission tomography;priority journal;spatial orientation;tauopathy;visual disorder,"Jellinger, K. A.;Grazer, A.;Petrovic, K.;Ropele, S.;Alpi, G.;Kapeller, P.;Ströbel, T.;Schmidt, R.",2011,,,0,
3599,Organic bases of late-life depression: a critical update,"Late-life depression (LLD) is frequently associated with cognitive impairment and increases the risk of subsequent dementia. Cerebrovascular disease, deep white matter lesions, Alzheimer disease (AD) and dementia with Lewy bodies (DLB) have all been hypothesized to contribute to this increased risk, and a host of studies have looked at the interplay between cerebrovascular disease and LLD. This has resulted in new concepts of LLD, such as ""vascular depression"", but despite multiple magnetic resonance imaging (MRI) studies in this field, the relationship between structural changes in human brain and LLD is still controversial. While pathological findings of suicide in some elderly persons revealed multiple lacunes, small vessel cerebrovascular disease, AD-related lesions or multiple neurodegenerative pathologies, recent autopsy data challenged the role of subcortical lacunes and white matter lesions as major morphological substrates of depressive symptoms as well as poorer executive function and memory. Several neuropathological studies, including a personal clinico-pathological study in a small cohort of elderly persons with LLD and age-matched controls confirmed that lacunes, periventricular and deep white matter demyelination as well as AD-related lesions are usually unrelated to the occurrence of LLD. In the same line, neuropathological data show that early-onset depression is not associated with an acceleration of age-related neurodegenerative changes. Very recent data on the critical role of glia-modulating neuronal dysfunction and degeneration in depression are discussed.","Aged;Aged, 80 and over;Brain/ pathology;Case-Control Studies;Cognition Disorders/ etiology;Depression/ complications;Female;Humans;Magnetic Resonance Imaging;Male","Jellinger, K. A.",2013,Jul,10.1007/s00702-012-0945-1,0,
3600,Lower cardiac output is associated with greater white matter hyperintensities in older adults with cardiovascular disease,"OBJECTIVES: To preliminarily examine the association between cardiac output, a measure of systemic blood flow, and structural brain magnetic resonance imaging indices of white matter hyperintensities (WMHs). DESIGN: Cross-sectional. SETTING: University medical setting. PARTICIPANTS: Thirty-six older adults without dementia with prevalent cardiovascular disease (aged 56-85). MEASUREMENTS: Cardiac output, WMHs. RESULTS: Partial correlations, adjusting for age and history of hypertension, yielded an inverse relationship between WMHs adjacent to subcortical nuclei and cardiac output (correlation coefficient=-0.48, P=.03); as cardiac output decreased, WMHs increased significantly. No significant associations were found between cardiac output and total WMHs or periventricular WMHs. CONCLUSION: These preliminary data suggest that systemic blood flow, measured according to cardiac output, is inversely associated with WMHs adjacent to the subcortical nuclei. Cerebrovascular degeneration and the chronicity of hypoperfusion may exacerbate the susceptibility of white matter integrity to alterations in blood flow in older adults.","Age Factors;Aged;Aged, 80 and over;Cardiac Output/ physiology;Cardiac Output, Low/ complications/physiopathology/ultrasonography;Cerebrovascular Circulation/ physiology;Cross-Sectional Studies;Echocardiography, Doppler;Female;Humans;Hypoxia, Brain/ etiology/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Prognosis;Prospective Studies;Risk Factors;Severity of Illness Index;Ventricular Function, Left/ physiology","Jefferson, A. L.;Tate, D. F.;Poppas, A.;Brickman, A. M.;Paul, R. H.;Gunstad, J.;Cohen, R. A.",2007,Jul,10.1111/j.1532-5415.2007.01226.x,0,
3601,Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study,"BACKGROUND: Systemic inflammation is associated with ischemia and Alzheimer disease (AD). We hypothesized that inflammatory biomarkers would be associated with neuroimaging markers of ischemia (i.e., white matter hyperintensities [WMH]) and AD (i.e., total brain volume [TCB]). METHODS: MRI WMH and TCB were quantified on 1,926 Framingham Offspring participants free from clinical stroke, TIA, or dementia (mean age 60 +/- 9 years; range 35 to 85 years; 54% women) who underwent measurement of a circulating inflammatory marker panel, including CD40 ligand, C-reactive protein, interleukin-6 (IL-6), soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, myeloperoxidase, osteoprotegerin (OPG), P-selectin, tumor necrosis factor-alpha (TNFalpha), and tumor necrosis factor receptor II. To account for head size, both TCB (TCBV) and WMH (WMH/TCV) were divided by total cranial volume. We used multivariable linear regression to relate 10 log-transformed inflammatory biomarkers to brain MRI measures. RESULTS: In multivariable models, inflammatory markers as a group were associated with TCBV (p < 0.0001) but not WMH/TCV (p = 0.28). In stepwise models adjusted for clinical covariates with backwards elimination of markers, IL-6 and OPG were inversely associated with TCBV; TNFalpha was inversely related to TCBV in a subset of 1,430 participants. Findings were similar in analyses excluding individuals with prevalent cardiovascular disease. The relations between TCBV and inflammatory markers were modified by both sex and age, and generally were more pronounced in men and in older individuals. CONCLUSIONS: Although our observational cross-sectional data cannot establish causality, they are consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age.","Adult;Age Distribution;Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/blood/*drug therapy/pathology;Biomarkers/analysis/blood;Brain/*pathology/physiopathology;Brain Ischemia/blood/*etiology/pathology;Cardiovascular Diseases/complications;Cross-Sectional Studies;Female;Humans;Inflammation/*complications/*diagnosis/physiopathology;Inflammation Mediators/analysis/*blood;Interleukin-6/analysis/blood;Magnetic Resonance Imaging;Male;Middle Aged;Osteoprotegerin/analysis/blood;Sex Distribution;Tumor Necrosis Factor-alpha/analysis/blood","Jefferson, A. L.;Massaro, J. M.;Wolf, P. A.;Seshadri, S.;Au, R.;Vasan, R. S.;Larson, M. G.;Meigs, J. B.;Keaney, J. F., Jr.;Lipinska, I.;Kathiresan, S.;Benjamin, E. J.;DeCarli, C.",2007,Mar 27,10.1212/01.wnl.0000257815.20548.df,0,
3602,Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters,"The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer’s Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters (n = 69, 75 ± 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 ± 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume.",,"Jefferson, A. L.;Gifford, K. A.;Damon, S.;Chapman, G. W.;Liu, D.;Sparling, J.;Dobromyslin, V.;Salat, D.",2015,4,,0,
3603,Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study,"BACKGROUND: Cross-sectional epidemiological and clinical research suggests that lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults. METHODS AND RESULTS: A total of 1039 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, and dementia formed our sample (age, 69+/-6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, antihypertensive medication, diabetes mellitus, cigarette smoking, cardiovascular disease history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac magnetic resonance imaging-assessed cardiac index (cardiac output divided by body surface area) to incident all-cause dementia and Alzheimer disease (AD). Over the median 7.7-year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each 1-SD unit decrease in cardiac index increased the relative risk of both dementia (hazard ratio [HR]=1.66; 95% confidence interval [CI], 1.11-2.47; P=0.013) and AD (HR=1.65; 95% CI, 1.07-2.54; P=0.022). Compared with individuals with normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02-4.19; P=0.044). If participants with clinically prevalent cardiovascular disease and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34-6.36; P=0.007) and AD (HR=2.87; 95% CI, 1.21-6.80; P=0.016) compared with individuals with normal cardiac index. CONCLUSION: Lower cardiac index is associated with an increased risk for the development of dementia and AD.","Aged;Aged, 80 and over;Alzheimer Disease/ epidemiology;Cardiac Output, Low/ complications;Cross-Sectional Studies;Dementia/ epidemiology;Female;Follow-Up Studies;Humans;Incidence;Male;Massachusetts;Middle Aged;Risk Factors","Jefferson, A. L.;Beiser, A. S.;Himali, J. J.;Seshadri, S.;O'Donnell, C. J.;Manning, W. J.;Wolf, P. A.;Au, R.;Benjamin, E. J.",2015,Apr 14,10.1161/circulationaha.114.012438,0,
3604,Semantic impairment in stroke aphasia versus semantic dementia: a case-series comparison,"Different neuropsychological populations implicate diverse cortical regions in semantic memory: semantic dementia (SD) is characterized by atrophy of the anterior temporal lobes whilst poor comprehension in stroke aphasia is associated with prefrontal or temporal-parietal infarcts. This study employed a case-series design to compare SD and comprehension-impaired stroke aphasic patients directly on the same battery of semantic tests. Although the two groups obtained broadly equivalent scores, they showed qualitatively different semantic deficits. The SD group showed strong correlations between different semantic tasks--regardless of input/output modality--and substantial consistency when a set of items was assessed several times. They were also highly sensitive to frequency/familiarity and made coordinate and superordinate semantic errors in picture naming. These findings support the notion that amodal semantic representations degrade in SD. The stroke aphasia group also showed multimodal deficits and consistency across different input modalities, but inconsistent performance on tasks requiring different types of semantic processing. They were insensitive to familiarity/frequency--instead, tests of semantic association were influenced by the ease with which relevant semantic relationships could be identified and distractors rejected. In addition, the aphasic patients made associative semantic errors in picture naming that SD patients did not make. The aphasic patients' picture naming performance improved considerably with phonemic cues suggesting that these patients retained knowledge that could not be accessed without contextual support. We propose that semantic cognition is supported by two interacting principal components: (i) a set of amodal representations (which progressively degrade in SD) and (ii) executive processes that help to direct and control semantic activation in a task-appropriate fashion (which are dysfunctional in comprehension-impaired stroke aphasic patients).",Adult;Aged;Anomia/etiology/pathology;Aphasia/etiology/pathology/*psychology;Comprehension;Cues;Decision Making;Dementia/pathology/*psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prefrontal Cortex/pathology;Semantics;Stroke/*complications;Temporal Lobe/pathology,"Jefferies, E.;Lambon Ralph, M. A.",2006,Aug,10.1093/brain/awl153,0,
3605,Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study,"BACKGROUND AND PURPOSE: Previous studies of cardiovascular risk factors and white matter hyperintensity (WMH) on brain MRI have been limited by the failure to exclude symptomatic cerebrovascular disease and dementia or by the use of semiquantitative rather than quantitative methods to measure WMH volume (WMHV). We examined the relationship between Framingham Stroke Risk Profile (FSRP) and WMHV measured quantitatively in a stroke and dementia-free subset of the Framingham Offspring Cohort. METHODS: Brain MRI was performed in 1814 members of the Framingham Offspring Cohort. Pixel-based quantitative measures of WMHV corrected for head size were obtained using a semiautomated algorithm. WMHV was not normally distributed and therefore was log-transformed (LWMHV). The FSRP and its component risk factors measured a mean of 7.5 years before MRI were related to both continuous measures of LWMHV and to the presence of large volumes of LWMHV (LWMHV-large). All analyses were adjusted for age and sex. RESULTS: FSRP was strongly associated with LWMHV and LWMHV-large. Age, smoking, history of cardiovascular disease, hypertension, and left ventricular hypertrophy by electrocardiogram were all significantly related to LWMHV or LWMHV-large. CONCLUSIONS: FSRP and several cardiovascular risk factors were related to both WMHV measured continuously and to a categorical designation of large volumes of WMH. These findings provide strong evidence of a vascular basis for WMH.","Adult;Aged;Aged, 80 and over;Brain/*pathology;Female;Humans;Leukoaraiosis/*pathology;*Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Stroke/*epidemiology","Jeerakathil, T.;Wolf, P. A.;Beiser, A.;Massaro, J.;Seshadri, S.;D'Agostino, R. B.;DeCarli, C.",2004,Aug,10.1161/01.str.0000135226.53499.85,0,
3606,Variation of selective gray and white matter atrophy in Huntington's disease,"The relationship between the extent of local gray/white matter atrophy, genetic load, and clinical impairment was studied in Huntington's disease (HD) by means of voxel-based morphometry. T1-weighted brain images from 33 patients (mean age 49.5, range 25-73 years) with HD duration of 1 to 15 years were analyzed by correlation of each voxel intensity with the number of CAG triplets and the UHDRS-motor score (P < 0.001). The CAG number correlated inversely with gray matter intensity in the caudate nuclei and with white matter intensity in the both postcentral gyri and the right cerebellum. The UHDRS-motor score correlated inversely with the atrophy of both caudates, right hippocampus, calcarine fissure, and with the white matter along the fourth and lateral ventricles. While atrophy of the caudate nucleus was related to a higher number of CAG triplets and higher UHDRS-motor score, atrophy in other parts of the brain covaried with the two parameters differently: higher genetic load was associated with greater loss of cortical somatosensory projections and the worse UHDRS-motor score was accompanied by increased atrophy of the internal capsule, lower brainstem, hippocampus, and visual cortex. According to our results, the genetic load in HD predicts partially the extent of selective gray/white brain matter atrophy, which is then reflected in the severity of motor impairment. © 2007 Movement Disorder Society.",,"Jech, R.;Klempíř, J.;Vymazal, J.;Židovská, J.;Klempířová, O.;Růžička, E.;Roth, J.",2007,15,,0,
3607,Managing depression in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (Cadasil): A case report,,acetylsalicylic acid plus clopidogrel;donepezil;etiracetam;lamotrigine;sertraline;adult;anhedonia;anxiety;ataxia;CADASIL;case report;cerebrovascular accident;cognitive defect;computer assisted tomography;concentration loss;depression;diabetes mellitus;drug dose increase;fatigue;hemianopia;hopelessness;human;hyperlipidemia;insomnia;letter;loss of appetite;male;middle aged;Mini Mental State Examination;Montreal cognitive assessment;nuclear magnetic resonance imaging;obesity;posterior reversible encephalopathy syndrome;posttraumatic stress disorder;seizure;sleep disordered breathing;vitamin D deficiency,"Jazi, A. N.;Shebak, S. S.;Tingler, W. L.",2016,,,0,
3608,Multi-infarct dementia: a computed tomographic study,CT Scan of 30 patients with multi-infarct dementia (MID) were compared with age- and sex-matched controls. Infarcts were seen in 93% of MID cases and 10% of controls. A marked difference in the occurrence of white matter low attenuation was seen between the groups. All the parameters of cerebral atrophy studied showed a statistically significant correlation with the presence of dementia.,"Brain/*radiography;Dementia, Multi-Infarct/*radiography;Female;Humans;Male;Middle Aged;*Tomography, X-Ray Computed","Jayakumar, P. N.;Taly, A. B.;Shanmugam, V.;Nagaraja, D.;Arya, B. Y.",1989,Apr,,0,
3609,Computed tomography (CT) in late infantile metachromatic leucodystrophy,"Computed tomographic features of 7 cases of the late infantile form of MLD confirmed by sural nerve biopsy are presented. Diffuse symmetrical white matter, low attenuation of the cerebral parenchyma was the common feature. Hypodensity of the temporal lobes and the cerebellar hemispheres are 2 features which have not been reported earlier. Three patients had brainstem atrophy without evidence of cerebral atrophy. Awareness of the various CT features of MLD may help in more definitive radiological diagnosis of the disease and to differentiate it from other dysmyelinating diseases of the central nervous system.",brain atrophy;clinical article;computer analysis;computer assisted tomography;dementia;human;metachromatic leukodystrophy;nerve biopsy;preschool child;priority journal,"Jayakumar, P. N.;Aroor, S. R.;Jha, R. K.;Arya, B. Y. T.",1989,,,0,
3610,[Neurologic changes in the white matter of the brain in dementia] Zmiany neurologiczne w istocie bialej mozgu w otepieniu,"Neuroradiologic white-matter lesions (WML) found in CT and NMR were evaluated in 30 demented patients and 12 dementia-free subjects aged over 65 years. NMR revealed more WML signs than CT. All NMR results of demented patients demonstrated abnormalities (brain atrophy and/or WML), while 15.4% patients with dementia had normal CT scan. WML in CT were found more often among male than female demented patients. No dependence between the intensity of dementia symptoms, age of subjects, age of onset of cognitive impairment, risk for vascular diseases, and the presence of WML in CT and NMR was found.","Aged;Alzheimer Disease/complications/ pathology;Brain/diagnostic imaging/ pathology;Dementia/complications/ pathology;Female;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/ etiology;Magnetic Resonance Spectroscopy;Male;Nerve Fibers, Myelinated/ pathology;Tomography, X-Ray Computed","Jarema, M.",1990,Mar-Apr,,0,
3611,[Neurologic changes in the white matter of the brain in dementia],"Neuroradiologic white-matter lesions (WML) found in CT and NMR were evaluated in 30 demented patients and 12 dementia-free subjects aged over 65 years. NMR revealed more WML signs than CT. All NMR results of demented patients demonstrated abnormalities (brain atrophy and/or WML), while 15.4% patients with dementia had normal CT scan. WML in CT were found more often among male than female demented patients. No dependence between the intensity of dementia symptoms, age of subjects, age of onset of cognitive impairment, risk for vascular diseases, and the presence of WML in CT and NMR was found.","Aged;Alzheimer Disease/complications/*pathology;Brain/*pathology/radiography;Dementia/complications/*pathology;Female;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/*etiology;Magnetic Resonance Spectroscopy;Male;Nerve Fibers, Myelinated/*pathology;Tomography, X-Ray Computed","Jarema, M.",1990,Mar-Apr,,0,
3612,CT and MRI white-matter lesions in Alzheimer's disease,,aged;Alzheimer disease;brain injury;clinical article;computer analysis;computer assisted tomography;human;nuclear magnetic resonance imaging;white matter,"Jarema, M.",1989,,,0,
3613,Vascular factors in suspected normal pressure hydrocephalus,"Objective: We examined clinical and imaging findings of suspected idiopathic normal pressure hydrocephalus (iNPH) in relation to vascular risk factors and white matter lesions (WMLs), using a nested case-control design in a representative, population-based sample. Methods: From a population-based sample, 1,235 persons aged 70 years or older were examined with CT of the brain between 1986 and 2000. We identified 55 persons with hydrocephalic ventricular enlargement, i.e., radiologic findings consistent with iNPH. Among these, 26 had clinical signs that fulfilled international guideline criteria for probable iNPH. These cases were labeled suspected iNPH. Each case was matched to 5 controls from the same sample, based on age, sex, and study cohort. Data on risk factors were obtained from clinical examinations and the Swedish Hospital Discharge Register. History of hypertension, diabetes mellitus (DM), smoking, overweight, history of coronary artery disease, stroke/TIA, and WMLs on CT were examined. Risk factors associated with iNPH with a p value <0.1 in χ 2 tests were included in conditional logistic regression models. Results: In the regression analyses, suspected iNPH was related to moderate to severe WMLs (odds ratio [OR] 5.2; 95% confidence interval [CI]: 1.5-17.6), while hydrocephalic ventricular enlargement was related to hypertension (OR 2.7; 95% CI: 1.1-6.8), moderate to severe WMLs (OR 6.5; 95% CI: 2.1-20.3), and DM (OR 4.3; 95% CI: 1.1-16.3). Conclusions: Hypertension, WMLs, and DM were related to clinical and imaging features of iNPH, suggesting that vascular mechanisms are involved in the pathophysiology. These findings might have implications for understanding disease mechanisms in iNPH and possibly prevention.",,"Jaraj, D.;Agerskov, S.;Rabiei, K.;Marlow, T.;Jensen, C.;Guo, X.;Kern, S.;Wikkelsø, C.;Skoog, I.",2016,16,,0,
3614,Retinal red spots and white-matter lesions in a 60-year-old man,,adult;apraxia;article;ataxia;brain damage;case report;cerebrospinal fluid examination;dementia;dysarthria;hemiparesis;human;leukoencephalopathy;male;neurologic examination;nuclear magnetic resonance imaging;priority journal;retina neovascularization;retinopathy;seizure;cerebrovascular accident;white matter,"Jansen, F. E.;Van Schooneveld, M. J.;Frijns, C. J. M.",2010,,,0,
3615,[Eleven years of autopsy on account of Creutzfeldt-Jakob disease in the Netherlands],"To describe our experience with the diagnostics of Creutzfeldt-Jakob disease (CJD) and other prion diseases in the Netherlands over a period of 11 years (1997-2007). Retrospective. In the period 1997-2007 autopsies were carried out on 280 patients with probable or possible CJD at the Dutch Surveillance Center for Prion Diseases in Utrecht. We registered clinical details, results of additional investigations such as EEG, MRI and cerebrospinal fluid tests, and outcomes of neurological investigations. The contribution of the different disorders within this group was estimated retrospectively. A prion disease was diagnosed in 146 patients (52%) with probable or possible CJD. 133 (91%) of these had the sporadic form. 2 patients were diagnosed with the 'variant CJD' (caused by bovine spongiform encephalopathy). 5 patients were diagnosed as having an iatrogenic form of CJD and 6 patients had a genetic form of the disease. A different disease was diagnosed in 134 patients (48%), such as Alzheimer disease (40%), multi-infarct dementia (13%), neoplasm (10%) and Lewy body dementia (8%). In this group, periodic sharp wave complexes were observed on EEG in 17 patients (13%), most frequently in those with Alzheimer disease. The 14-3-3 protein test on cerebrospinal fluid was positive in 28 of these patients (21%), most frequently in patients with vascular dementia and Alzheimer disease. In all cases of an unclear clinical picture suggestive of neurodegenerative disease, prion disease must be considered. Periodic sharp wave complexes on EEG and a positive 14-3-3 protein test on cerebrospinal fluid alone are not diagnostic of CJD.",protein 14 3 3;adolescent;adult;aged;Alzheimer disease;article;autopsy;cerebrospinal fluid;Creutzfeldt Jakob disease;differential diagnosis;diffuse Lewy body disease;electroencephalography;female;human;male;middle aged;multiinfarct dementia;Netherlands;retrospective study;sentinel surveillance,"Jansen, C.;Schuur, M.;Spliet, W. G.;van Gool, W. A.;van Duijn, C. M.;Rozemuller, A. J.",2009,,,0,
3616,"Dementia, deep white matter damage and hypertension: 'Binswanger's disease'","The clinical and neuropathological features are reported of 7 patients with organic intellectual impairment or dementia, hypertension and ischaemic destruction predominantly of the deep white matter of the cerebral hemispheres resembling that seen in infarction. The white matter changes have been dismissed as rare in the past, usually under the name of Binswanger's disease or subcortical arteriosclerotic encephalopathy, and without much concern for hypertension. There are now indications that this sort of case may not be uncommon. It can be suspected in life on CT scans. The accuracy of assessment of the pathological substrate of organic dementia, and therefore the strategies of research and treatment, might well benefit from further clinicopathological studies.",Binswanger encephalopathy;cardiovascular system;case report;central nervous system;dementia;hypertension,"Janota, I.",1981,,,0,
3617,Head to head comparison of [(18)F] AV-1451 and [(18)F] THK5351 for tau imaging in Alzheimer's disease and frontotemporal dementia,"PURPOSE: Tau accumulation is a core pathologic change in various neurodegenerative diseases including Alzheimer's disease and frontotemporal lobar degeneration-tau. Recently, tau positron emission tomography tracers such as [(18)F] AV-1451 and [(18)F] THK5351 have been developed to detect tau deposition in vivo. In the present study, we performed a head to head comparison of these two tracers in Alzheimer's disease and frontotemporal dementia cases and aimed to investigate which tracers are better suited to image tau in these disorders. METHODS: A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We recruited eight participants (two Alzheimer's disease, four frontotemporal dementia and two normal controls) who underwent magnetic resonance image, amyloid positron emission tomography with [(18)F]-Florbetaben and tau positron emission tomography with both THK5351 and AV-1451. To measure regional AV1451 and THK5351 uptakes, we used the standardized uptake value ratios by dividing mean activity in target volume of interest by mean activity in the cerebellar hemispheric gray matter. RESULTS: Although THK5351 and AV-1451 uptakes were highly correlated, cortical uptake of AV-1451 was more striking in Alzheimer's disease, while cortical uptake of THK5351 was more prominent in frontotemporal dementia. THK5351 showed higher off-target binding than AV-1451 in the white matter, midbrain, thalamus, and basal ganglia. CONCLUSIONS: AV-1451 is more sensitive and specific to Alzheimer's disease type tau and shows lower off-target binding, while THK5351 may mirror non-specific neurodegeneration.",Alzheimer's disease;Av-1451;Frontotemporal dementia;Thk5351;Tau,"Jang, Y. K.;Lyoo, C. H.;Park, S.;Oh, S. J.;Cho, H.;Oh, M.;Ryu, Y. H.;Choi, J. Y.;Rabinovici, G. D.;Kim, H. J.;Moon, S. H.;Jang, H.;Lee, J. S.;Jagust, W. J.;Na, D. L.;Kim, J. S.;Seo, S. W.",2018,Mar,,0,
3618,Early- vs late-onset subcortical vascular cognitive impairment,"OBJECTIVE: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function. METHODS: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset >/=65 years) groups. All patients underwent neuropsychological tests, 3T brain MRI, and [(11)C] Pittsburgh compound B (PiB)-PET. We compared pathologic burden such as small vessel disease and amyloid burden; structural changes such as structural network, cortical thickness, and hippocampal volume; and cognitive function between EO-SVCI and LO-SVCI. RESULTS: EO-SVCI patients had more lacunes, while LO-SVCI patients had higher PiB standardized uptake value ratios. EO-SVCI patients exhibited more severe structural network disruptions in the frontal area, while LO-SVCI patients exhibited more severe cortical and hippocampal atrophy. Although disease severity did not differ between the 2 groups, frontal-executive dysfunction was more severe in EO-SVCI patients. CONCLUSIONS: EO-SVCI patients showed more vascular related factors, while LO-SVCI patients exhibited more Alzheimer disease-related characteristics. The greater number of lacunes in EO-SVCI might account for the more severe frontal network disruption and frontal-executive dysfunction, while the greater amyloid burden in LO-SVCI might account for the more severe cortical and hippocampal atrophy. Our findings suggest that the age at onset is a crucial factor that determines distinct features in SVCI patients, such as pathologic burden, structural changes, and cognitive function.",,"Jang, Y. K.;Kwon, H.;Kim, Y. J.;Jung, N. Y.;Lee, J. S.;Lee, J.;Chin, J.;Im, K.;Jeon, S.;Lee, J. M.;Seong, J. K.;Kim, J. H.;Kim, S.;Choe, Y. S.;Lee, K. H.;Kim, S. T.;Kim, J. S.;Lee, J. H.;Na, D. L.;Seo, S. W.;Kim, H. J.",2016,Feb 9,10.1212/wnl.0000000000002357,0,
3619,White matter hyperintensities as a new predictor of driving cessation in the elderly: a Clinical Research Center for Dementia of South Korea (CREDOS) Study,"Brief introduction to the research question: Driving requires the integration of high-level cognitive functions, perception, and motor function [1,2]. Cognitive impairment may contribute to increase risk of unsafe driving performance [3]. Also, motor dysfunction in Parkinson disease or Alzheimer's disease is well known predictors of driving performance [4,5]. White matter hyperintensities (WMH) changes on brain MRI are associated structural brain changes along with cognitive and motor performance. Therefore, WMH are known as the factors related with cognitive decline and motor dysfunction which might lower driving performance synergistically, but researches on the effect of WMH to driving capacity are scarce yet. Aim of the study: In this study, we investigated a nationwide multicenter hospital-based prospective cohort study to reveal the association of WMH and driving cessation in the elderly. The purpose of this study was to discern if the degree of WMH could predict the risk of driving cessation with or without motor and cognitive functions in the elderly. Methods: Participants (n = 540) were drawn from a nationwide, multicenter, hospital-based, longitudinal cohort study of dementia aimed to understand the characteristics of Korean patients with dementia from November 2005 to April 2013. Each participant underwent clinical evaluations, neuropsychological tests, and interview for caregiver including driving capacity which was categorized as 'now driving' and 'driving cessation (driving before, not now)'. A total 540 participants were divided into three groups (389 mild, 116 moderate, and 35 severe) depending on the degree of WMH. The same evaluations of them were followed after each year. A chi<sup>2</sup> test was performed to examine trends in categorical data and an analysis of variance (ANOVA) was performed for continuous variables, to compare the groups' scores on demographics and driving status. To evaluate the relative effects of WMH on driving with or without the mediation of cognition and motor function, a structured equation model (SEM) was used. We used generalized estimating equation (GEE) to estimate longitudinal effects of WMH on change in driving status. Summary of results: According to the degree of WMH, it showed statistical differences in age, sex, and motor dysfunction in Poster Table 1. It showed strongly statistical differences in driving cessation according to the degree of WMH (p<0.001). In a SEM, greater baseline degree of WMH was directly associated with driving cessation regardless of cognitive and motor dysfunction (beta = -0.110, p<0.001). In GEE models controlling for age, sex, education, cognitive, and motor dysfunction, the more severe changes of the degree of WMH was associated with the faster change from 'now driving' state to 'driving cessation' state over time in the elderly (beta = -0.508, p<0.001). Conclusions: In both cross-sectional and longitudinal aspects, the degree of WMH might be one of the predictive factors for driving cessation in the elderly, reflecting both motor and cognitive functions or independently.",aged;analysis of variance;caregiver;chi square test;clinical evaluation;clinical research;clinical trial;cognitive defect;cohort analysis;controlled clinical trial;controlled study;hospital;human;interview;major clinical study;motor dysfunction;motor performance;multicenter study;neuropsychological test;nuclear magnetic resonance imaging;sexual education;South Korea;statistical model;white matter,"Jang, M.;Son, S. J.",2017,,,0,
3620,"A comprehensive visual rating scale of brain magnetic resonance imaging: application in elderly subjects with Alzheimer's disease, mild cognitive impairment, and normal cognition","BACKGROUND: Brain magnetic resonance imaging (MRI) shows cerebral structural changes. However, a unified comprehensive visual rating scale (CVRS) has seldom been studied. Thus, we combined brain atrophy and small vessel disease scales and used an MRI template as a CVRS. OBJECTIVE: The aims of this study were to design a simple and reliable CVRS, validate it by investigating cerebral structural changes in clinical groups, and made comparison to the volumetric measurements. METHODS: Elderly subjects (n = 260) with normal cognition (NC, n = 65), mild cognitive impairment (MCI, n = 101), or Alzheimer's disease (AD, n = 94) were evaluated with brain MRI according to the CVRS of brain atrophy and small vessel disease. Validation of the CVRS with structural changes, neuropsychological tests, and volumetric analyses was performed. RESULTS: The CVRS revealed a high intra-rater and inter-rater agreement and it reflected the structural changes of subjects with NC, MCI, and AD better than volumetric measures (CVRS-coronal: F = 13.5, p < 0.001; CVRS-axial: F = 19.9, p < 0.001). The area under the receiver operation curve (aROC) of the CVRS showed higher accuracy than volumetric analyses. (NC versus MCI aROC: CVRS-coronal, 0.777; CVRS-axial, 0.773; MCI versus AD aROC: CVRS-coronal, 0.680; CVRS-axial, 0.681). CONCLUSION: The CVRS can be used clinically to conveniently measure structural changes of brain. It reflected cerebral structural changes of clinical groups and correlated with the age better than volumetric measures.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology;Analysis of Variance;Atrophy/pathology;Brain/ pathology;Female;Hemorrhage/etiology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/complications/ pathology;Neuropsychological Tests;ROC Curve;Statistics as Topic","Jang, J. W.;Park, S. Y.;Park, Y. H.;Baek, M. J.;Lim, J. S.;Youn, Y. C.;Kim, S.",2015,,10.3233/jad-142088,0,
3621,Effect of white matter hyperintensity on medial temporal lobe atrophy in Alzheimer's disease,"BACKGROUND: Medial temporal atrophy (MTA) is a recognized marker of Alzheimer's disease (AD), and white matter hyperintensities (WMH) are frequently observed on MRI of AD. The purpose of this study was to understand the role of WMH in MTA. METHODS: Subjects were 94 probable AD patients and 51 cognitively normal subjects. WMH was assessed based on the severity of deep WMH (DWMH) and periventricular WMH (PWMH). Each structural volume was evaluated using the Individual Brain Atlases from the Statistical Parametric Mapping Toolbox. RESULTS: There were no significant differences between subjects with and without WMH in terms of general cognitive function scales. Subjects with AD with WMH had decreased volume in the bilateral orbital frontal gyrus, frontal rectus gyrus, and olfactory gyrus, but not in the medial temporal lobes. After correcting for differences in DWMH, age and Clinical Dementia Rating Scale (CDR), AD with PWMH showed decreased volumes in the bilateral hippocampi. AD with PWMH showed worse scores on the Clinical Dementia Rating-Sum of Boxes and Barthel-ADL, and some frontal executive function tests. Those with DWMH did not show any reductions in the medial temporal lobes. CONCLUSION: WMH in AD is not associated with medial temporal lobe atrophy, but PWMH is independently correlated with hippocampal volume reduction.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/*pathology;Atrophy/etiology/pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Temporal Lobe/*pathology","Jang, J. W.;Kim, S.;Na, H. Y.;Ahn, S.;Lee, S. J.;Kwak, K. H.;Lee, M. A.;Hsiung, G. Y.;Choi, B. S.;Youn, Y. C.",2013,,10.1159/000345999,0,
3622,CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of Alzheimer disease,"OBJECTIVE: The diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) must be improved before widespread clinical use. This study aimed to determine whether CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF Abeta42 alone. METHODS: The study comprised three different cohorts (n = 1182) in whom CSF levels of Abeta42, Abeta40, and Abeta38 were assessed. CSF Abetas were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid ((18)F-flutemetamol) positron emission tomography (PET) imaging (n = 215) or clinical diagnosis (n = 967) of well-characterized patients. RESULTS: When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios were significantly better predictors of abnormal amyloid PET than CSF Abeta42. Lower Abeta42, Abeta42/Abeta40, and Abeta42/Abeta38 ratios, but not Abeta40 and Abeta38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower Abeta38, Abeta40, and Abeta42, but not the ratios, correlated with non-AD-specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the Abeta42/Abeta40 and Abeta42/Abeta38 ratios showed increased accuracy compared to Abeta42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all Abetas (including Abeta42) were decreased. INTERPRETATION: The CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios are significantly better than CSF Abeta42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non-AD dementias. The ratios reflect AD-type pathology better, whereas decline in CSF Abeta42 is also associated with non-AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF Abeta42 should be used in the clinical work-up of AD.",,"Janelidze, S.;Zetterberg, H.;Mattsson, N.;Palmqvist, S.;Vanderstichele, H.;Lindberg, O.;van Westen, D.;Stomrud, E.;Minthon, L.;Blennow, K.;Hansson, O.",2016,Mar,10.1002/acn3.274,0,
3623,Genetic risk factors for longitudinal changes in structural MRI in former organolead workers,"This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted. APOE epsilon3/epsilon4 and epsilon4/epsilon4 genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACE and high-density lipoprotein; VDR and diabetes) on brain volume decline. The VDR FokI ff genotype was associated with an increase in WML (no association for APOE or ACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.",,"James, B. D.;Caffo, B.;Stewart, W. F.;Yousem, D.;Davatzikos, C.;Schwartz, B. S.",2011,,10.4061/2011/362189,0,
3624,Haemorrhagic stroke or hyperglycaemia?,"A 56-year-old woman with no medical history was admitted with acute onset hemiballistic-choreiform movements of right extremity. On admission, her serum glucose and osmolality were elevated. Her glycosylated haemoblobin (HbA1c) was 17.9 with average blood sugars of 467 mg/dL. A CT scan of the brain revealed unilateral hyperintensities in the basal ganglia. A complete stroke work-up, including MRI and MR angiography of brain was otherwise unrevealing. Subcutaneous insulin was instituted, which led to complete resolution of her symptoms within 48 h of hospital admission. She was readmitted 4 weeks after her initial discharge for similar, but less severe, symptoms. This time her HbA1c was 13.9 with an average blood sugar of 352 mg/dL. A repeat MRI demonstrated a persistent abnormal signal within the left basal ganglia without infarct. She was started on subcutaneous insulin. Her symptoms improved but did not resolve. Haloperidol and gabapentin were initiated and she was again discharged after stabilisation to a rehabilitation centre as per physiotherapy recommendations.",alanine aminotransferase;alkaline phosphatase;aspartate aminotransferase;chloride;hemoglobin A1c;insulin;potassium;sodium;thyrotropin;thyroxine;abnormal laboratory result;acquired immune deficiency syndrome;adult;article;blurred vision;brain hemorrhage;case report;cerebrovascular accident;chorea;computer assisted tomography;differential diagnosis;disease association;female;follow up;Friedreich ataxia;Glasgow coma scale;headache;hemiballism;hemichorea hemiballismus;human;Huntington chorea;hyperglycemia;hyperthyroidism;hypothyroidism;increased appetite;insulin treatment;liver failure;malignant neoplastic disease;muscle weakness;neuroacanthocytosis;non ketotic hyperglycemia;nuclear magnetic resonance imaging;paresthesia;polydipsia;polyuria;poststreptococcal autoimmune disorder;priority journal;senile chorea;systemic lupus erythematosus;toxoplasmosis;treatment outcome;unpleasant sensation;weight reduction,"Jalota, L.;Luber, S.;Shrestha, R.;Patel, A.",2013,,,0,
3625,Hidden dysfunctioning in subacute stroke,"BACKGROUND AND PURPOSE: Determining cognitive dysfunctioning (CDF) after stroke is an important issue because it influences choices for management in terms of return to previous activities. Because previous research in subacute stroke has shown important variations in CDF rates, we aimed to describe the frequency and neuropsychological profile of CDF in subacute stroke outside dementia. We used a large battery of tests to screen any potentially hidden CDF. METHODS: Patients with Mini-Mental State Examination scores >or=23 were prospectively and consecutively included 2 weeks after a first-ever ischemic brain infarct. Stroke features were based on MRI. Four domains were evaluated: instrumental and executive functions, episodic memory, and working memory (WM). Patients were scored using means and compared with education- and age-matched control subjects. Then we attributed Z-scores for each test and each domain. The most relevant cognitive tests characterizing CDF were determined using logistic regression. RESULTS: Among 177 patients (mean age, 50.6 years), 91.5% failed in at least one cognitive domain. WM was the most impaired domain (87.6%) with executive functions (64.4%), episodic memory (64.4%), and instrumental functions (24.9%) being relatively preserved. CDF was associated with age, education, depression, neurological deficit, and leukoaraiosis in bivariate analysis. Using logistic regression, WM tests and age predicted CDF (Modified Paced Auditorial Serial Addition Test: OR=0.96 CI=0.93 to 0.98; Owen-spatial-WM: OR=1.07 CI=1.02 to 1.12; age: OR=0.96 CI=0.93 to 0.98). CONCLUSIONS: CDF appears to be almost constant, although underestimated, in subacute stroke. WM could reflect some hidden dysfunctioning, which may interfere with rehabilitation and return to work. Clinical routine may include WM tests in young patients with mild stroke.",Adult;Aged;Case-Control Studies;Cognition/physiology;Cognition Disorders/*etiology/physiopathology/*psychology;Female;Humans;Intelligence Tests;Logistic Models;Male;Middle Aged;Prospective Studies;Sensitivity and Specificity;Stroke/*complications/physiopathology/*psychology,"Jaillard, A.;Naegele, B.;Trabucco-Miguel, S.;LeBas, J. F.;Hommel, M.",2009,Jul,10.1161/strokeaha.108.541144,0,
3626,Predicting cognitive dysfunctioning in nondemented patients early after stroke,"BACKGROUND: Cognitive dysfunctioning (CDF) is an important issue in stroke, interfering with recovery and social dysfunctioning. We aimed to investigate the clinical and imaging correlates of CDF in patients with a first-ever subacute ischemic stroke and no dementia. METHODS: We evaluated CDF 15 days after stroke in a prospective cohort of consecutive patients with a Mini Mental State Examination score > or =23 using a comprehensive neuropsychological battery. CDF was ranked into 3 categories according to Z scores calculated for each test and adjusted for age and education. CDF was analyzed in relation to stroke features. Imaging was assessed using MRI. An ordinal regression procedure was used to determine the clinical correlates of CDF and to compute probabilities. RESULTS: Cognitive evaluation was achieved in 177 consecutive patients (age 50.0 +/- 16.0 years). In bivariate analysis, CDF was associated with age, low level of education, depression, neurological deficit at day 15, stroke subtype, arterial territory and leukoaraiosis but not with stroke volume or location. The predictors of CDF were NIHSS score at day 15 (OR = 1.35; 95% CI = 1.05-1.73), middle cerebral artery infarct (OR = 2.96; 95% CI = 1.30-6.73), depression interacting with left stroke side (OR = 1.09; 95% CI = 1.03-1.15), and female gender interacting with high level of education (OR = 0.209; 95% CI = 0.085-0.514). CONCLUSIONS: Stroke features correlate with CDF in nondemented patients. These simple criteria may help to predict CDF at bedside in the subacute phase after stroke and to recommend a neuropsychological evaluation for patients' management. Modeling CDF soon after stroke using simple neurological criteria may be a useful tool for designing clinical trials.",Adult;Aged;Brain/blood supply;Brain Infarction/complications/psychology;Cerebrovascular Circulation;Cognition Disorders/diagnosis/ epidemiology;Cohort Studies;Depression/complications;Educational Status;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Prospective Studies;Retrospective Studies;Risk Factors;Sex Characteristics;Stroke/classification/ complications/ psychology;Time Factors,"Jaillard, A.;Grand, S.;Le Bas, J. F.;Hommel, M.",2010,,10.1159/000289344,0,
3627,"DTI studies in patients with Alzheimer's disease, mild cognitive impairment, or normal cognition with evaluation of the intrinsic background gradients","INTRODUCTION: The objective of the study was to explore the impact of the background gradients on diffusion tensor (DT) magnetic resonance imaging (DT-MRI) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), or cognitively normal (CN) aging. METHODS: Two DT-MRI sets with positive and negative polarities of the diffusion-sensitizing gradients were obtained in 15 AD patients, 18 MCI patients, and 16 CN control subjects. The maps of mean diffusivity (MD) and fractional anisotropy (FA) were computed separately for positive (p: pMD and pFA) and negative (n: nMD and nFA) polarities, and we computed the geometric mean (gm) of the DT-MRI to obtain the gmFA and gmMD with reducing the background gradient effects. Regional variations were assessed across the groups using one-way analysis of variance. RESULTS: Increased regional gmMD values in the AD subjects, as compared to the regional gmMD values in the MCI and CN subjects, were found primarily in the frontal, limbic, and temporal lobe regions. We also found increased nMD and pMD values in the AD subjects compared to those values in the MCI and CN subjects, including in the temporal lobe and the left limbic parahippocampal gyrus white matter. Results of comparisons among the three methods showed that the left limbic parahippocampal gyrus and right temporal gyrus were the increased MD in the AD patients for all three methods. CONCLUSION: Background gradients affect the DT-MRI measurements in AD patients. Geometric average diffusion measures can be useful to minimize the intrinsic local magnetic susceptibility variations in brain tissue.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Brain/ pathology;Case-Control Studies;Cognition;Diffusion Magnetic Resonance Imaging;Female;Frontal Lobe/pathology;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Male;Mild Cognitive Impairment/ pathology;Temporal Lobe/pathology","Jahng, G. H.;Xu, S.;Weiner, M. W.;Meyerhoff, D. J.;Park, S.;Schuff, N.",2011,Oct,10.1007/s00234-011-0845-3,0,
3628,Neuropathological basis of magnetic resonance images in aging and dementia,"OBJECTIVE: Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present. METHODS: This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes. Neuropathological examination quantified CVD parenchymal pathology, AD pathology (defined as Consortium to Establish a Registry for Alzheimer's Disease scores and Braak and Braak stage), and hippocampal sclerosis. Subjects were pathologically classified as 12 healthy control subjects, 46 AD, 14 CVD, 9 mixed AD/CVD, and 12 cognitively impaired patients without significant AD/CVD pathology. Multivariate models tested associations between magnetic resonance and pathological findings across the entire sample. RESULTS: Pathological correlates of cortical gray matter volume were AD, subcortical vascular pathology, and arteriosclerosis. Hippocampal volume was related to AD pathology and hippocampal sclerosis, and the effects of hippocampal sclerosis were greater for subjects with low levels of AD pathology. White matter hyperintensities were related to age and to white matter pathology. Number of MRI lacunes was related to subcortical vascular pathology. INTERPRETATION: In this clinical setting, the presence of lacunes and white matter changes provide a good signal for vascular disease. The neuropathological basis of MR defined cerebral cortical and hippocampal atrophy in aging and dementia is complex, with several pathological processes converging on similar brain structures that mediate cognitive decline.","Age Factors;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology/physiopathology;Arteriosclerosis/pathology;Atrophy/pathology/physiopathology;Brain/blood supply/ pathology/physiopathology;Brain Infarction/pathology/physiopathology;Cerebral Cortex/blood supply/pathology/physiopathology;Cohort Studies;Dementia, Vascular/ pathology/physiopathology;Diagnosis, Differential;Female;Hippocampus/blood supply/pathology/physiopathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging/ statistics & numerical data;Male;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests","Jagust, W. J.;Zheng, L.;Harvey, D. J.;Mack, W. J.;Vinters, H. V.;Weiner, M. W.;Ellis, W. G.;Zarow, C.;Mungas, D.;Reed, B. R.;Kramer, J. H.;Schuff, N.;DeCarli, C.;Chui, H. C.",2008,Jan,10.1002/ana.21296,0,
3629,SPECT Perfusion Imaging in the Diagnosis of Dementia,"Single-photon emission computed tomography (SPECT) imaging has provided the practicing clinician with a method of studying brain function in patients with dementia. A large and growing number of papers report the experiences of a number of laboratories in the use of this technique in the evaluation of demented patients. Studies from several laboratories comparing patients with Alzheimer's disease to control subjects report sensitivity and specificity of SPECT perfusion imaging to be in the 80% vicinity. In addit1on, a number of studies suggest that the dementias that show the greatest similarities in perfusion patterns to Alzheimer's disease are multi-Infarct dementia and dementia associated with ParkinSon's d1sease. Although considerable data exist to guide the physician, a rigorous scientific approach to studying patients in a prospective, unselected clinical sample, with autopsy confirmation of the diagnosis, is needed to define clearly the utility of the technique in diagnosing dementias.",glucose;acquired immune deficiency syndrome;article;autopsy;blood flow;brain function;brain infarction;brain perfusion;brain scintiscanning;clinical feature;controlled clinical trial (topic);Creutzfeldt Jakob disease;dementia;diagnostic test accuracy study;diagnostic value;differential diagnosis;frontal lobe;frontotemporal dementia;glucose brain level;human;Huntington chorea;lactic acidosis;Mini Mental State Examination;mitochondrial encephalopathy;Parkinson disease;Pick presenile dementia;positron emission tomography;sensitivity and specificity;single photon emission computed tomography;subdural hematoma;white matter,"Jagust, W. J.;Johnson, K. A.;Holman, B. L.",1995,,10.1111/jon19955s1s45,0,3630
3630,SPECT Perfusion Imaging in the Diagnosis of Dementia,"Single-photon emission computed tomography (SPECT) imaging has provided the practicing clinician with a method of studying brain function in patients with dementia. A large and growing number of papers report the experiences of a number of laboratories in the use of this technique in the evaluation of demented patients. Studies from several laboratories comparing patients with Alzheimer's disease to control subjects report sensitivity and specificity of SPECT perfusion imaging to be in the 80% vicinity. In addit1on, a number of studies suggest that the dementias that show the greatest similarities in perfusion patterns to Alzheimer's disease are multi-Infarct dementia and dementia associated with ParkinSon's d1sease. Although considerable data exist to guide the physician, a rigorous scientific approach to studying patients in a prospective, unselected clinical sample, with autopsy confirmation of the diagnosis, is needed to define clearly the utility of the technique in diagnosing dementias.",,"Jagust, W. J.;Johnson, K. A.;Holman, B. L.",1995,1,,0,
3631,"MRI, CT, SPECT, PET: their use in diagnosing dementia","The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests. Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing. Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD.","Alzheimer Disease/diagnosis;Dementia/ diagnosis;Diagnosis, Differential;Humans;Magnetic Resonance Imaging;Tomography, Emission-Computed;Tomography, Emission-Computed, Single-Photon;Tomography, X-Ray Computed","Jagust, W. J.;Eberling, J. L.",1991,Feb,,0,
3632,The diagnosis of dementia with single photon emission computed tomography,"Single photon emission computed tomography is a practical modality for the study of physiologic cerebral activity in vivo. We utilized single photon emission computed tomography and N-isopropyl-p-iodoamphetamine iodine 123 to evaluate regional cerebral blood flow in nine patients with Alzheimer's disease (AD), five healthy elderly control subjects, and two patients with multi-infarct dementia. We found that all subjects with AD demonstrated flow deficits in temporoparietal cortex bilaterally, and that the ratio of activity in bilateral temporoparietal cortex to activity in the whole slice allowed the differentiation of all patients with AD from both the controls and from the patients with multi-infarct dementia. Furthermore, this ratio showed a strong correlation with disease severity in the AD group. Single photon emission computed tomography appears to be useful in the differential diagnosis of dementia and reflects clinical features of the disease.","Aged;Alzheimer Disease/*radionuclide imaging;Amphetamines;Brain/radionuclide imaging;*Cerebrovascular Circulation;Dementia/*radionuclide imaging;Female;Humans;Iodine Radioisotopes;Iofetamine;Male;Middle Aged;Parietal Lobe/blood supply/*radionuclide imaging;Temporal Lobe/blood supply/*radionuclide imaging;*Tomography, Emission-Computed","Jagust, W. J.;Budinger, T. F.;Reed, B. R.",1987,Mar,,0,
3633,Central obesity and the aging brain,"BACKGROUND: Central adiposity as an indicator of visceral fat is linked to vascular and metabolic factors that in turn are related to cognitive decline and dementia. OBJECTIVE: To determine whether larger waist-hip ratio (WHR) is associated with structural brain changes that underlie cognitive decline and dementia. DESIGN: Cross-sectional analysis of an epidemiologic cohort study of cognitive and functional decline (Sacramento Area Latino Study on Aging). SETTING: California Central Valley. PARTICIPANTS: A total of 112 individuals selected from an ongoing cohort study of 1789 older Latino individuals. Baseline anthropomorphic measures (WHR) and measurements of fasting blood glucose, cholesterol, and insulin levels and blood pressure were obtained. MAIN OUTCOME MEASURES: Baseline magnetic resonance images were analyzed quantitatively to determine the hippocampal volumes in the right and left hemispheres and rated for the percentage of white matter hyperintensities. RESULTS: Greater WHR (P = .02) and older age (P<.001) were negatively related to hippocampal volumes. The WHR and age were positively related to white matter hyperintensities (P = .02 and P = .001, respectively). A 1-SD increase in WHR was associated with a 0.2-SD decrease in hippocampal volume and a 27% increase in white matter hyperintensities. These relationships were not affected by adjustment for body mass index, total cholesterol, fasting blood glucose, and insulin levels or systolic blood pressure in the models. CONCLUSION: A larger WHR may be related to neurodegenerative, vascular, or metabolic processes that affect brain structures underlying cognitive decline and dementia.","Aged;Aged, 80 and over;Aging;Brain/ pathology;Brain Diseases/ etiology;Cross-Sectional Studies;Humans;Magnetic Resonance Imaging;Middle Aged;Obesity/ complications;Waist-Hip Ratio/ adverse effects","Jagust, W.;Harvey, D.;Mungas, D.;Haan, M.",2005,Oct,10.1001/archneur.62.10.1545,0,
3634,Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment,"Alzheimer's disease (AD) is increasingly considered as a disconnection syndrome. Previous studies of the structural connectome in early AD stages have focused on mild cognitive impaired subjects (MCI), considering them as a homogeneous group. We studied 168 subjects from the Alzheimer's Disease Neuroimaging Initiative database (116 MCI and 52 cognitively normal subjects). Biomarker-based stratification using amyloid biomarkers (AV45 PET) and neurodegeneration biomarkers (MRI and FDG PET) led to 4 subgroups based on amyloid positivity (A+/-) and neurodegeneration positivity (N+/-): A-N-, A+N-, A-N+, and A+N+. Using diffusion MRI, we showed that both MCI A-N+ and MCI A+N+ subjects displayed an alteration of the white matter in the fornix and a significant bihemispheric network of decreased connections. These network alterations in MCI A+N+ are stronger and more focal than those of MCI A-N+. Only MCI A+N+ subjects exhibited specific changes in hippocampal connectivity and an AD-like alteration pattern. Our results indicate that the connectome disintegration pattern of MCI subgroups differ with respect to brain amyloid and neurodegeneration. Each of these 2 AD biomarkers induces a connectome alteration that is maximal when they coexist.","0 (Biomarkers);Amyloid angiopathy;Aged;Aged, 80 and over;Alzheimer Disease/ complications/diagnostic imaging;Biomarkers;Cerebral Amyloid Angiopathy/ complications/diagnostic imaging;Cognition/ physiology;Cognitive Dysfunction/diagnostic imaging/ etiology/pathology/ psychology;Connectome;Diffusion Magnetic Resonance Imaging;Female;Hippocampus/diagnostic imaging/physiopathology;Humans;Male;Middle Aged;Nerve Degeneration/ complications/diagnostic imaging;Positron-Emission Tomography;Alzheimer's disease;Mci;Network analysis;Structural connectome","Jacquemont, T.;De Vico Fallani, F.;Bertrand, A.;Epelbaum, S.;Routier, A.;Dubois, B.;Hampel, H.;Durrleman, S.;Colliot, O.;Alzheimer's Disease Neuroimaging, Initiative",2017,Jul,,0,
3635,Fragile X-associated tremor/ataxia syndrome - FXTAS,"It is now clearly established that the FMR1 gene is associated with two distinct pathogenic mechanisms: loss and gain of function. The ""loss of function"" of the FMR1 gene leads to the absence of FMRP protein (coded by FMR1). This lack of FMRP is responsible for the fragile X syndrome (FXS), which is the most common cause of inherited mental retardation. On the other hand, the toxic ""gain of function"" of FMR1 is responsible for two late onset disorders: premature ovarian failure and fragile X-associated tremor/ataxia syndrome (FXTAS) which was reported for the first time in 2001. The core clinical features of FXTAS are progressive cerebellar gait ataxia and intention tremor; associated features include neuropsychiatric abnormalities, parkinsonism, autonomic dysfunction and peripheral neuropathy. Cognitive changes range from mild frontal executive and memory deficits to global dementia. Neuroradiological features of FXTAS include prominent white-matter disease in the periventricular, subcortical and middle cerebellar peduncles (MCPs) on T(2)-weighted MR imaging. The principal neuropathologic characteristic of FXTAS are eosinophilic, ubiquitin-positive inclusions located in the nuclei of neurons and astrocytes in broad distribution throughout the brain and spinal column. There is prominent white-matter involvement with patchy loss of axons, myelin and associated astroglial cells. Recent studies suggest that the penetrance and severity of the neurological disorder is a function of the number of CGG repeats; namely that the penetrance among carriers of larger pre-mutation alleles is greater than among carriers of smaller premutation alleles. Screening for the FMR1 premutation in populations of patients with movement disorders found that the frequency of premutation alleles was 13 times greater (OR = 12.4; 95% CI: 1.6, 93.5) in patients with cerebellar ataxia (16/1049) than expected based on its prevalence in the general population (2%; 16/818 for age-of-onset >50 years of age). As the FMR1-related phenotypes expand, genetic counselling for fragile X families becomes increasingly complex. Clinicians should inform their patients that their relatives are at risk for a variety of disorders including movement disorder and premature ovarian failure. In addition, women of child-bearing age are at risk of having a child with FXS and they should systematically be referred to a geneticist.",,"Jacquemont, S.",2006,December,,0,
3636,Confluent thalamic hyperintensities in CADASIL,"BACKGROUND: CADASIL is responsible for diffuse hyperintensities in the white matter on FLAIR images. These lesions are often associated with focal lesions in the basal ganglia such as lacunar infarctions. The prevalence and significance of diffuse or confluent thalamic hyperintensities (CTH) remain unknown. METHODS: The frequency of hyperintensities on FLAIR images in the thalamus was assessed in 147 CADASIL patients, and signal abnormalities on both FLAIR and T(1)-weighted images were categorized as focal/punctuate or diffuse/confluent by the same reader. The areas of increased diffusion were also analyzed on apparent diffusion coefficient maps. The association of CTH with vascular risk factors, the main clinical manifestations of the disease and MRI markers (brain parenchymal fraction, volume of white matter hyperintensities, volume of lacunar infarcts and number of microbleeds) was analyzed with generalized linear regression models. RESULTS: CTH were detected in 12% of the CADASIL subjects in association with hypointensities on T(1)-weighted images. CTH corresponded to areas of increased diffusion on apparent diffusion coefficient maps. CTH were found significantly associated with age and independently related to the volume of white matter hyperintensities but not to that of lacunar infarctions or to cerebral atrophy after adjustment for age and sex. No significant association was found between CTH and global cognitive performances. CONCLUSION: CTH are observed on FLAIR images in a sizeable proportion of CADASIL patients. They are mainly related to the extent of white matter hyperintensities and do not correlate with cognitive decline. Demyelination and/or loss of glial cells appear to be the most plausible cause of these confluent signal changes in the thalamus.",Adult;Basal Ganglia/pathology;Brain Infarction/pathology;CADASIL/ pathology;Cell Nucleus/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prevalence;Retrospective Studies;Thalamus/ pathology,"Jacqmin, M.;Herve, D.;Viswanathan, A.;Guichard, J. P.;During, M.;Dichgans, M.;Chabriat, H.",2010,Aug,10.1159/000319607,0,
3637,Computed tomography in the elderly. 2. Senile dementia: Diagnosis and functional impairment,"Clinical, psychometric and computed tomographic (CT) data are presented on three groups of elderly subjects: 50 normals, 40 patients with senile dementia and 41 suffering from affective disorder. Demented subjects showed significantly more CT evidence of cerebral atrophy than non-demented subjects, but there was considerable overlap. Although patients with a history or clinical signs of cerebral infarction were specifically excluded, such infarcts were found more often in CT scans of the dementia subjects than in the others, particularly when the diastolic blood pressure was raised. When correlating cognitive impairment with CT changes, ventricular size emerged as more important in the dementia patients, in contrast to the controls, in whom cortical atrophy was related to lower scores on a cognitive test. Other interesting findings included an inverse relationship between cortical atrophy and paranoid delusions.",brain dysfunction;central nervous system;chronic brain disease;computer assisted tomography;dementia;diagnosis;major clinical study,"Jacoby, R. J.;Levy, R.",1980,,,0,
3638,The association between white matter hyperintensities and executive decline in mild cognitive impairment is network dependent,"White matter hyperintensities (WMH) in Mild Cognitive Impairment (MCI) have been associated with impaired executive functioning, although contradictory findings have been reported. The aim of this study was to examine whether WMH location influenced the relation between WMH and executive functioning in MCI participants (55-90 years) in the European multicenter memory-clinic-based DESCRIPA study, who underwent MRI scanning at baseline (N = 337). Linear mixed model analysis was performed to test the association between WMH damage in three networks (frontal-parietal, frontal-subcortical and frontal-parietal-subcortical network) and change in executive functioning over a 3-year period. WMH in the frontal-parietal and in the frontal-parietal-subcortical network were associated with decline in executive functioning. However, the frontal-subcortical network was not associated with change in executive functioning. Our results suggest that parietal WMH are a significant contributor to executive decline in MCI and that investigation of WMH in the cerebral networks supporting cognitive functions provide a new way to differentiate stable from cognitive declining MCI individuals. © 2012 Elsevier Inc.",adult;aged;article;Europe;executive function;female;frontal cortex;human;male;mild cognitive impairment;nerve cell network;neuroimaging;nuclear magnetic resonance imaging;parietal cortex;priority journal;subcortex;white matter;white matter hyperintensity,"Jacobs, H. I. L.;Visser, P. J.;Van Boxtel, M. P. J.;Frisoni, G. B.;Tsolaki, M.;Papapostolou, P.;Nobili, F.;Wahlund, L. O.;Minthon, L.;Frölich, L.;Hampel, H.;Soininen, H.;van de Pol, L.;Scheltens, P.;Tan, F. E. S.;Jolles, J.;Verhey, F. R. J.",2012,,,0,
3639,Patterns of gray and white matter changes in individuals at risk for Alzheimer's disease,"Structural brain changes precede cognitive and clinical symptoms in Alzheimer's disease (AD). We aimed to examine the gray and white matter tissue changes in individuals with memory decline over a 12-year period, who might be at risk for AD. The participants were selected from the longitudinal Maastricht Aging Study based on their scores on the verbal word learning task. A group with profound memory decline over a 12-year period (n = 20) was identified and matched with a group that did not meet this criterion (n = 20). All of the participants underwent MRI scanning. Diffusion tensor imaging and cortical thickness analyses were performed to investigate the white and gray matter differences respectively. We found decreased white matter integrity in the memory decline group compared to the control group in frontal and parietal brain regions and in several cortico-cortical and cortico-subcortical tracts. Cortical thinning in the memory decline group was found in frontal, parietal, medial temporal and occipital areas. These results showed similarities with the structural brain changes observed in early AD. Thus, not only may cognitive changes be detected years before the clinical diagnosis, but typical gray and white matter changes appear to be present in older people with memory decline as well. This suggests that a combination of cognitive decline and structural brain changes might be an ideal biomarker for AD pathogenesis.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Cognition Disorders/ pathology;Early Diagnosis;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Risk Factors","Jacobs, H. I.;van Boxtel, M. P.;Gronenschild, E. H.;Williams, V. J.;Burgmans, S.;Uylings, H. B.;Jolles, J.;Verhey, F. R.",2012,Nov,,0,
3640,Decreased gray matter diffusivity: a potential early Alzheimer's disease biomarker?,"BACKGROUND: Gray matter atrophy, an important biomarker for early Alzheimer's disease, might be due to white matter changes within gray matter. METHODS: Twenty older participants with significant memory decline over a 12-year period (T12) were matched to 20 nondeclining participants. All participants were magnetic resonance imaging scanned at T12. Cortical thickness and diffusion tensor imaging analyses were performed. RESULTS: Lower cortical thickness values were associated with lower diffusion values in frontal and parietal gray matter areas. This association was only present in the memory decline group. The cortical thickness-diffusion tensor imaging correlations showed significant group differences in the posterior cingulate gyrus, precuneus, and superior frontal gyrus. CONCLUSIONS: Decreased gray matter diffusivity in the posterior cingulate/precuneus area might be a disease-specific process and a potential new biomarker for early Alzheimer's disease. Future studies should validate its potential as a biomarker and focus on cellular changes underlying diffusivity changes in gray matter.","Aged;Alzheimer Disease/ pathology;Anisotropy;Biomarkers;Brain/ pathology;Early Diagnosis;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male","Jacobs, H. I.;van Boxtel, M. P.;Gronenschild, E. H.;Uylings, H. B.;Jolles, J.;Verhey, F. R.",2013,Jan,10.1016/j.jalz.2011.11.004,0,
3641,"Association between white matter microstructure, executive functions, and processing speed in older adults: The impact of vascular health","Cerebral white matter damage is not only a commonly reported consequence of healthy aging, but is also associated with cognitive decline and dementia. The aetiology of this damage is unclear; however, individuals with hypertension have a greater burden of white matter signal abnormalities (WMSA) on MR imaging than those without hypertension. It is therefore possible that elevated blood pressure (BP) impacts white matter tissue structure which in turn has a negative impact on cognition. However, little information exists about whether vascular health indexed by BP mediates the relationship between cognition and white matter tissue structure. We used diffusion tensor imaging to examine the impact of vascular health on regional associations between white matter integrity and cognition in healthy older adults spanning the normotensive to moderate-severe hypertensive BP range (43-87 years; N = 128). We examined how white matter structure was associated with performance on tests of two cognitive domains, executive functioning (EF) and processing speed (PS), and how patterns of regional associations were modified by BP and WMSA. Multiple linear regression and structural equation models demonstrated associations between tissue structure, EF and PS in frontal, temporal, parietal, and occipital white matter regions. Radial diffusivity was more prominently associated with performance than axial diffusivity. BP only minimally influenced the relationship between white matter integrity, EF and PS. However, WMSA volume had a major impact on neurocognitive associations. This suggests that, although BP and WMSA are causally related, these differential metrics of vascular health may act via independent pathways to influence brain structure, EF and PS. © 2011 Wiley Periodicals, Inc.",,"Jacobs, H. I.;Leritz, E. C.;Williams, V. J.;Van Boxtel, M. P.;Elst, W. V. D.;Jolles, J.;Verhey, F. R.;McGlinchey, R. E.;Milberg, W. P.;Salat, D. H.",2013,January,,0,
3642,White matter hyperintensities are positively associated with cortical thickness in Alzheimer's disease,"White matter hyperintensities are associated with an increased risk of Alzheimer's disease (AD). White matter hyperintensities are believed to disconnect brain areas. We examined the topographical association between white matter hyperintensities and cortical thickness in controls, mild cognitive impairment (MCI), and AD patients. We examined associations between white matter hyperintensities and cortical thickness among 18 older cognitively healthy participants, 18 amnestic MCI, and 17 mild AD patients. These associations were cluster-size corrected for multiple comparisons. In controls, a positive association between white matter hyperintensities and cortical thickness was found in lateral temporal gyri. In MCI patients, white matter hyperintensities were positively related to cortical thickness in frontal, temporal, and parietal areas. Positive associations between white matter hyperintensities and cortical thickness in AD patients were confined to parietal areas. The results of the interaction group by white matter hyperintensities on cortical thickness were consistent with the findings of positive associations in the parietal lobe for MCI and AD patients separately. In the frontal areas, controls and AD patients showed inverse associations between white matter hyperintensities and cortical thickness, while MCI patients still showed a positive association. These results suggest that a paradoxical relationship between white matter hyperintensities and cortical thickness could be a consequence of neuroinflammatory processes induced by AD-pathology and white matter hyperintensities. Alternatively, it might reflect a region-specific and disease-stage dependent compensatory hypertrophy in response to a compromised network.","Aged;Alzheimer Disease/*pathology;Brain/*pathology;Frontal Lobe/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/*pathology;Nerve Fibers, Myelinated/*pathology;Organ Size;Parietal Lobe/pathology;Temporal Lobe/pathology;Compensation;cortical thickness;dementia;hypertrophy;inflammation;white matter hyperintensities","Jacobs, H. I.;Clerx, L.;Gronenschild, E. H.;Aalten, P.;Verhey, F. R.",2014,,10.3233/jad-131232,0,
3643,White matter integrity and reaction time intraindividual variability in healthy aging and early-stage Alzheimer disease,"Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the reaction time (RT) distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging.","Aged;Aged, 80 and over;Aging/*physiology;Alzheimer Disease/pathology/*physiopathology;Case-Control Studies;Cerebrum/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Reaction Time/*physiology","Jackson, J. D.;Balota, D. A.;Duchek, J. M.;Head, D.",2012,Feb,10.1016/j.neuropsychologia.2011.11.024,0,
3644,MR findings in normal-pressure hydrocephalus: Significance and comparison with other forms of dementia,"This study was undertaken to identify findings on magnetic resonance (MR) imaging that might possibly differentiate among several dementia states in the elderly or predict response to shunt therapy in patients with normal-pressure hydrocephalus (NPH). The MR findings were retrospectively reviewed in 54 patients who were divided into four clinical categories: NPH (17 patients), obstructive hydrocephalus (eight patients), Alzheimer disease (eight patients), and non-Alzheimer dementia (21 patients). Three MR findings were evaluated in each case: increased periventricular (PVS) and white matter (WMS) signal on T2-weighted images, CSF flow void sign (CFVS) in the aqueduct, and corpus callosum thinning. Neither the PVS/WMS nor corpus callosum thinning patterns were useful for distinguishing among the four clinical groups. At low field strength, the absence of a marked or moderate CFVS, however, may militate against a diagnosis of NPH. All 17 patients with NPH underwent a shunt procedure after the MR study. A better response to shunt therapy occurred in patients without WMS and with more severe PVS.",,"Jack Jr, C. R.;Mokri, B.;Laws Jr, E. R.;Houser, O. W.;Baker, H. L.;Petersen, R. C.",1987,1987,,0,
3645,"Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50–95 years: a cross-sectional study","Background A new classification for biomarkers in Alzheimer's disease and cognitive ageing research is based on grouping the markers into three categories: amyloid deposition (A), tauopathy (T), and neurodegeneration or neuronal injury (N). Dichotomising these biomarkers as normal or abnormal results in eight possible profiles. We determined the clinical characteristics and prevalence of each ATN profile in cognitively unimpaired individuals aged 50 years and older. Methods All participants were in the Mayo Clinic Study of Aging, a population-based study that uses a medical records linkage system to enumerate all individuals aged 50–89 years in Olmsted County, MN, USA. Potential participants are randomly selected, stratified by age and sex, and invited to participate in cognitive assessments; individuals without medical contraindications are invited to participate in brain imaging studies. Participants who were judged clinically as having no cognitive impairment and underwent multimodality imaging between Oct 11, 2006, and Oct 5, 2016, were included in the current study. Participants were classified as having normal (A−) or abnormal (A+) amyloid using amyloid PET, normal (T−) or abnormal (T+) tau using tau PET, and normal (N−) or abnormal (N+) neurodegeneration or neuronal injury using cortical thickness assessed by MRI. We used the cutoff points of standard uptake value ratio (SUVR) 1·42 (centiloid 19) for amyloid PET, 1·23 SUVR for tau PET, and 2·67 mm for MRI cortical thickness. Age-specific and sex-specific prevalences of the eight groups were determined using multinomial models combining data from 435 individuals with amyloid PET, tau PET, and MRI assessments, and 1113 individuals who underwent amyloid PET and MRI, but not tau PET imaging. Findings The numbers of participants in each profile group were 165 A−T−N−, 35 A−T+N−, 63 A−T−N+, 19 A−T+N+, 44 A+T−N−, 25 A+T+N−, 35 A+T−N+, and 49 A+T+N+. Age differed by ATN group (p<0·0001), ranging from a median 58 years (IQR 55–64) in A–T–N– and 57 years (54–64) in A–T+N– to a median 80 years (75–84) in A+T–N+ and 79 years (73–87) in A+T+N+. The number of APOE ε4 carriers differed by ATN group (p=0·04), with carriers roughly twice as frequent in each A+ group versus the corresponding A– group. White matter hyperintensity volume (p<0·0001) and cognitive performance (p<0·0001) also differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant in most individuals who would be categorised as stage 2 or 3 preclinical Alzheimer's disease (A+T+N−, A+T−N+, and A+T+N+; 86% at age 65 years and 51% at age 80 years) or with suspected non-Alzheimer's pathophysiology (A−T+N−, A−T−N+, and A−T+N+; 92% at age 65 years and 78% at age 80 years). From age 50 years, A−T−N− prevalence declined and A+T+N+ and A−T+N+ prevalence increased. In both men and women, A−T−N− was the most prevalent until age late 70s. After about age 80 years, A+T+N+ was most prevalent. By age 85 years, more than 90% of men and women had one or more biomarker abnormalities. Interpretation Biomarkers of fibrillar tau deposition can be included with those of β-amyloidosis and neurodegeneration or neuronal injury to more fully characterise the heterogeneous pathological profiles in the population. Both amyloid- dependent and amyloid-independent pathological profiles can be identified in the cognitively unimpaired population. The prevalence of each ATN group changed substantially with age, with progression towards more biomarker abnormalities among individuals who remained cognitively unimpaired. Funding National Institute on Aging (part of the US National Institutes of Health), the Alexander Family Professorship of Alzheimer's Disease Research, the Mayo Clinic, and the GHR Foundation.",amyloid beta protein;biological marker;flortaucipir;Pittsburgh compound B;adjustment;adult;age;aged;Alzheimer disease;amyloidosis;article;beta amyloidosis;cognitive defect;controlled study;cortical thickness (brain);cross-sectional study;data analysis;female;human;major clinical study;male;middle aged;nerve degeneration;neuroimaging;nuclear magnetic resonance imaging;performance;positron emission tomography;precursor;prevalence;priority journal;sex ratio;tauopathy;white matter,"Jack, C. R.;Wiste, H. J.;Weigand, S. D.;Therneau, T. M.;Knopman, D. S.;Lowe, V.;Vemuri, P.;Mielke, M. M.;Roberts, R. O.;Machulda, M. M.;Senjem, M. L.;Gunter, J. L.;Rocca, W. A.;Petersen, R. C.",2017,,10.1016/s1474-4422(17)30077-7,0,
3646,FLAIR histogram segmentation for measurement of leukoaraiosis volume,"The purposes of this study were to develop a method to measure brain and white matter hyperintensity (leukoaraiosis) volume that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery (FLAIR) images and to assess the accuracy and reproducibility of the method. Whole-head synthetic image phantoms with manually introduced leukoaraiosis lesions of varying severity were constructed. These synthetic image phantom sets incorporated image contrast and anatomic features that mimicked leukoaraiosis found in real life. One set of synthetic image phantoms was used to develop the segmentation algorithm (FLAIR-histoseg). A second set was used to measure its accuracy. Test retest reproducibility was assessed in 10 elderly volunteers who were imaged twice. The mean absolute error of the FLAIR-histoseg method was 6.6% for measurement of leukoaraiosis volume and 1.4% for brain volume. The mean test retest coefficient of variation was 1.4% for leukoaraiosis volume and 0.3% for brain volume. We conclude that the FLAIR-histoseg method is an accurate and reproducible method for measuring leukoaraiosis and whole-brain volume in elderly subjects. © 2001 Wiley-Liss, Inc.",,"Jack, C. R.;O'Brien, P. C.;Rettman, D. W.;Shiung, M. M.;Xu, Y.;Muthupillai, R.;Manduca, A.;Avula, R.;Erickson, B. J.",2001,2001,,0,
3647,"Neurobrucellosis presenting with hearing loss, gait disturbances and diffuse white matter disease on brain magnetic resonance imaging (MRI)","PURPOSE : To report an unusual case of neurobrucellosis. METHODS : A 48-year-old man was admitted to Rafik Hariri University Hospital (RHUH) for progressive gait disturbances, hearing loss, and some episodes of chills without documented fever. The neurological examination showed gait ataxia, tremor in the legs and mild cognitive decline. The physical exam was otherwise normal. RESULTS : Magnetic resonance imaging (MRI) of brain showed diffuse, bilateral, confluent, subcortical, and periventricular white matter disease. Serum agglutination test (SAT) for Brucella was positive in blood and cerebrospinal fluid (CSF). The patient was treated with a combination of ceftriaxone for one month, and doxycycline and rifampicin for one year and his condition stabilized. Literature review was performed. The possible underlying pathophysiological mechanisms are discussed. CONCLUSION : Neurobrucellosis is a very rare complication of human brucellosis, and can present with a variety of central nervous system symptomatology (CNS) and MRI changes suggestive of leukoencephalopathy. Its diagnosis could be challenging and should always be suspected in patients presenting with CNS manifestations and/or diffuse white matter disease visualized on brain MRI, especially in Brucella endemic areas.",,"Jabbour, R. A.;Tabbarah, Z.",2011,April-June,,0,
3648,Two cases of Japanese CADASIL with corpus callosum lesion,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. In the present study, a Japanese CADASIL family was first reported with missense mutation of Arg141Cys of Notch3 and a unique lesion of corpus callosum. Upon neuropsychological examination, our case 1 showed only right-handed constructional apraxia associated with corpus callosum lesion. No other callosal disconnection signs were present. Sagittal T2 weighted image of case 1 showed multiple small lesions along with the pericallosal branches from the truncus to the posterior part of the splenium in the corpus callosum. Although detailed mapping of the corpus callosum for functional fractionation in humans remains incomplete, the constructional apraxia on the right may be related to callosal dysfunction from the truncus to the posterior part of the splenium in the corpus callosum.-CADASIL; corpus callosum; constructional apraxia © 2001 Tohoku University Medical Press.",,"Iwatsuki, K.;Murakami, T.;Manabe, Y.;Narai, H.;Warita, H.;Hayashi, T.;Abe, K.",2001,2001,,0,
3649,A case of neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions,"We report a 55-year-old woman with neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions. She showed a cryptogenic high fever and cerebral cortical symptoms such as perseveration, limb-kinetic apraxia and dementia. CSF study showed an increase of cell count and protein and a decrease of sugar. MRI showed diffuse T2-high signal intensity mainly in the subcortical white matter of left parieto-occipital lobes and basal ganglia. Her clinical signs greatly improved after administration of prednisolone. Her HLA type was not B51 but B54. Though our patient did not completely satisfy clinical criteria for neither neuro-Behçet's disease nor Sweet's syndrome, she showed partial features of both Behçet's disease and Sweet's syndrome.",gadolinium pentetate;glucose;HLA B antigen;prednisolone;protein;acute febrile neutrophilic dermatosis;adult;article;Behcet disease;case report;cerebrospinal fluid analysis;female;human;nuclear magnetic resonance imaging;single photon emission computer tomography;white matter,"Iwatsuki, K.;Deguchi, K.;Narai, H.;Hayashi, T.;Warita, H.;Manabe, Y.;Kashihara, K.;Abe, K.",2000,,,0,
3650,Senile onset frontotemporal lobar degeneration with TAR-DNA binding protein 43 proteinopathy primarily presenting with wasteful habits,"We present an autopsied case of a senile Japanese woman with sporadic frontotemporal lobar degeneration (FTLD) presenting as frontotemporal dementia. Disease onset was at the age of 70 and presented as a behaviour disorder, particularly involving wasteful habits. The patient had repeated incidents of making expensive purchases and then had difficulty making payments. Following these symptoms, she showed other changes of character such as lethargy and apathy. She gradually showed signs of parkinsonism including rigidity and bradykinesia, and in the terminal stage, an akinetic mutism state with quadriplegia in flexion was observed. Head magnetic resonance imaging revealed severe frontotemporal lobe atrophy with severe lateral ventricular dilatation and frontal white matter degeneration. At autopsy, the brain weighed 930g and the frontotemporal cerebral cortex showed neuron loss with gliosis, tissue rarefaction and spongiform change, particularly in the superficial layers. Pathologic degeneration was more severe in the anterior portion of the frontal lobe with extensive white matter degeneration. Immunostaining for phosphorylated TAR-DNA binding protein 43 (TDP-43) revealed numerous neuronal cytoplasmic inclusions and extensive short dystrophic neuritis, particularly in the frontotemporal cortex. Many TDP-43-positive cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. The patient was pathologically diagnosed with FTLD with TDP-43-positive inclusions (FTLD-TDP) without motor neuron disease. The immunohistochemical findings corresponded to type A of the FTLD-TDP pathology classification system. © 2013 Japanese Psychogeriatric Society.",,"Iwasaki, Y.;Mori, K.;Ito, M.;Tatsumi, S.;Mimuro, M.;Yoshida, M.",2013,December,,0,
3651,Clinicopathologic findings of argyrophilic grain dementia in a case of mild cognitive impairment converting to dementia,"An 84-year-old Japanese woman with no family history of dementia visited our memory clinic complaining of memory disturbance. Neurological examination revealed no apparent motor abnormalities, focal cerebral signs, parkinsonism, or cerebellar dysfunction. Hasegawa's Dementia Scale-Revised (HDS-R) and Mini mental state examination (MMSE) scores were 24 and 23 points, respectively. MRI revealed left-side-dominant dilatation of the inferior horn of the lateral ventricle. Although egocentric behavior was remarkable, no disturbance of intelligence was apparent at the first examination, and she was diagnosed as having mild cognitive impairment. Her memory disturbance and disorientation gradually worsened. Atrophy of the cerebrum and dilatation of the lateral ventricle advanced gradually on MRI. Two years later, she required care to perform activities of daily living. HDS-R and MMSE scores had dropped to 13 and 18 points, respectively, and conversion to dementia was diagnosed. Ability to perform 3D cube-copying was well preserved. The patient died due to acute myocardial infarction at the age of 87. The clinical diagnosis was Alzheimer disease. At autopsy, the brain weighed 1,250 g, and argyrophilic grains were widely observed in the limbic system, corresponding to Saito's stage III. Neuron loss, gliosis, spongiform change, and tissue rarefaction were recognized in the superficial layer of the parahippocampal gyrus. Ballooned neurons, pretangles, oligodendroglial coiled bodies, and neuropil threads were also observed. Neurofibrillary tangles and senile plaques, mainly consisting of diffuse plaque, were recognized as corresponding to Braak stage III and CERAD stage B, respectively. Neither Lewy nor Pick bodies were observed. Although mild phosphorylated TDP-43 immunoreactivity was observed, it was suspected to be due to secondary degeneration of tau deposition. The patient was diagnosed pathologically as having argyrophilic grain dementia. The clinical findings of the present patient reveal important observations that help to clinically discriminate between various dementias such as Alzheimer disease and argyrophilic grain dementia.",aged;argyrophilic grain dementia;article;autopsy;case report;dementia;fatality;female;Hasegawa Dementia Scale Revised;human;human tissue;memory disorder;mild cognitive impairment;Mini Mental State Examination;rating scale,"Iwasaki, Y.;Mori, K.;Ito, M.;Tatsumi, S.;Mimuro, M.;Yoshida, M.",2012,,,0,
3652,An autopsied case of unclassifiable sporadic four-repeat tauopathy presenting with parkinsonism and speech disturbances,"A 48-year-old Japanese woman experienced slow-onset parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities, bradykinesia and postural instability, although cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as fasciculation or electromyogram findings. She eventually reached the akinetic mutism state, and gastrostomy and tracheotomy were performed at 4years after onset. A clinical diagnosis of progressive supranuclear palsy was made prior to her death, which occurred 6years after onset. Post mortem examinations revealed that the brain weighed 1200g and showed atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with gliosis. Using hyperphosphorylated tau (AT-8) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT-8 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of sarkosyl-insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of microtubule-associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four-repeat tauopathy.",levodopa;adult;akinetic mutism;article;astrocyte;autopsy;bradykinesia;brain atrophy;brain blood flow;brain perfusion;brain size;cognitive defect;dentate nucleus;disease duration;electroencephalography;electromyogram;eye movement disorder;fasciculation;female;four repeat tauopathy;gait disorder;gastrostomy;genetic analysis;gliosis;globus pallidus;human;immunoelectron microscopy;immunohistochemistry;inferior olive;intelligence quotient;involuntary movement;Japanese (people);mental disease;middle aged;Mini Mental State Examination;motoneuron;motor unit potential;muscle rigidity;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;paresis;parkinsonism;personality disorder;priority journal;progressive supranuclear palsy;single photon emission computer tomography;speech disorder;substantia nigra;subthalamic nucleus;tauopathy;tracheotomy;Wechsler adult intelligence scale;Western blotting,"Iwasaki, Y.;Mori, K.;Ito, M.;Tatsumi, S.;Mimuro, M.;Kuwano, R.;Hasegawa, M.;Yoshida, M.",2016,,,0,
3653,Gerstmann-Sträussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course,"We describe an autopsied case of a Japanese woman with Gerstmann-Sträussler-Scheinker disease (GSS) presenting with a rapidly progressive clinical course. Disease onset occurred at the age of 54 with dementia and gait disturbance. Her clinical course progressively deteriorated until she reached a bedridden state with myoclonus 9 months after onset. Two months later, she reached the akinetic mutism state. Nasal tube feeding was introduced at this point and continued for several years. Electroencephalograms showed diffuse slowing without periodic sharp-wave complexes. Diffusion-weighted magnetic resonance imaging (MRI) showed widespread cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed a Pro to Leu point mutation at codon 102 with methionine homozygosity at codon 129. The patient died of respiratory failure after a total disease duration of 62 months. Neuropathologic examination revealed widespread spongiform change with numerous eosinophilic amyloid plaques (Kuru plaques) in the cerebral and cerebellar cortices by H & E staining. Diffuse myelin pallor with axon loss of the cerebral white matter, suggestive of panencephalopathic-type pathology, was observed. Numerous PrP immunopositive plaques and diffuse synaptic-type PrP deposition were extensively observed, particularly in the cerebral and cerebellar cortices. Western blot analysis of proteinase Kresistant PrP showed a characteristic band pattern with a small molecular band of 6 kDa. The reason for the similarity in clinicopathologic findings between the present case and Creutzfeldt-Jakob disease is uncertain; however, the existence of an unknown disease-modifying factor is suspected. © 2014 Dustri-Verlag Dr. K. Feistle.",,"Iwasaki, Y.;Mori, K.;Ito, M.;Nokura, K.;Tatsumi, S.;Mimuro, M.;Kitamoto, T.;Yoshida, M.",2014,2014,,0,
3654,An autopsied case of V180I Creutzfeldt-Jakob disease presenting with panencephalopathic-type pathology and a characteristic prion protein type,"A 73-year-old Japanese woman showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia. One year later she showed parkinsonism and corticobasal degeneration was initially suspected. On MRI, the left temporal neocortex seemed swollen on T2-weighted images in the initial stage, and a later high-signal intensity region was observed in the cerebral cortex in diffusion-weighted images. The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively. Consecutive electroencephalography revealed no periodic sharp-wave complexes. Prion protein (PrP) gene analysis revealed a valine to isoleucine point mutation at codon 180, and methionine homozygosity at codon 129. This patient's clinical symptoms and disease course were atypical for Creutzfeldt-Jakob disease (CJD), and a stable state with nasal tube-feeding lasted several years. She died of respiratory failure at the age of 81, 102 months after the onset. Autopsy revealed widespread spongiform degeneration with weak synaptic-type PrP deposition, confirming the diagnosis of genetic CJD. Neurons in the cerebral cortex were relatively preserved in number and hypertrophic astrocytosis was generally moderate for such long-term disease, but cerebral white matter showed diffuse severe myelin pallor with tissue rarefaction suggestive of panencephalopatic-type pathology. The cerebellar cortex was relatively well preserved with observation of mild spongiform change in the molecular layer, moderate neuron loss in the Purkinje neuron layer, and scattered small plaque-like PrP deposition. Western blot analysis of protease-resistant PrP showed a characteristic pattern without a diglycoform band. V180I CJD is an interesting form of genetic CJD with regards to the clinicopathologic, molecular and genetic findings. © 2011 Japanese Society of Neuropathology.",,"Iwasaki, Y.;Mori, K.;Ito, M.;Nagaoka, M.;Ieda, T.;Kitamoto, T.;Yoshida, M.;Hashizume, Y.",2011,October,,0,
3655,An autopsied case of corticobasal degeneration presenting with frontotemporal dementia followed by myoclonus,"A Japanese woman developed frontotemporal dementia (FTD)-like symptoms of abnormal behavior, such as stereotyped behavior and disinhibition. The patient developed these symptoms at the age of 59 years, although aphasia symptoms were not apparent at early disease stages. Progressive parkinsonism was dominant on the left side, and conspicuous myoclonus was recognized in the late disease stage. MRI indicated severe, right side-dominant frontotemporal lobe atrophy with white matter degeneration. Brainstem and cerebellar atrophy were also observed. The patient underwent gastrostomy 7 years after the onset of her symptoms and died at the age of 70 years. Neuropathological examination showed diffuse neuron loss with gliosis and tissue rarefaction in the frontotemporal lobe, particularly in the right anterior portion of the frontal lobe. Spongiform changes and ballooned neurons were also observed in the frontotemporal cortex, particularly in the superficial layer and deeper layers, respectively. Gallyas-Braak silver staining and anti-phosphorylated tau immunostaining indicated numerous argyrophilic and tau-positive structures, including pretangles, astrocytic plaques, coiled bodies and neuropil threads. We speculate that the myoclonus observed in the present case was at least partly caused by or related to the spongiform change and ballooned neurons in the cerebral cortex. The clinical phenotypes of corticobasal degeneration (CBD) vary considerably, and the clinical presentation of the present patient was compatible with frontal behavioral-spatial syndrome in the early disease stage. However, in the later disease stages, her symptoms were reflective of corticobasal syndrome. Because it is not rare for the clinical phenotype to change along with disease progression in cases of CBD, we should consider CBD in cases presenting with FTD at symptom onset.",antihypertensive agent;apolipoprotein E;DNA;prion protein;tau protein;abnormal behavior;adult;aged;akinetic mutism;Alzheimer disease;antigen binding;apathy;aphasia;argyrophilia;article;aspiration pneumonia;astrocyte;autopsy;behavior disorder;behavioral spatial syndrome;bradykinesia;brain atrophy;brain blood flow;brain cortex;brain stem;brain ventricle dilatation;case report;cause of death;cell loss;cerebellum atrophy;clinical article;clinical examination;clinical feature;coiled body;corticobasal degeneration;Creutzfeldt Jakob disease;daily life activity;degeneration;diffusion weighted imaging;disease course;disease severity;domestic cat;dystonic disorder;electroencephalogram;female;frontal lobe;frontotemporal dementia;frontotemporal lobe atrophy;gait disorder;gastrostomy;genetic analysis;gliosis;human;human tissue;immobility;immunohistochemistry;joint contracture;Lewy body;meal;medical history;middle aged;motor dysfunction;muscle rigidity;myoclonus;neighborhood;nerve cell;neuropathology;neuropil thread;nuclear magnetic resonance imaging;nursing home;parkinsonism;phenotypic variation;priority journal;protein phosphorylation;protein structure;quadriplegia;senile plaque;silver staining;single photon emission computed tomography;stereotypy;symptom;upper limb;wandering behavior;white matter lesion,"Iwasaki, Y.;Mori, K.;Ito, M.;Mimuro, M.;Yoshida, M.",2017,,10.1111/neup.12398,0,
3656,"An autopsied case of progressive supranuclear palsy, initially diagnosed as spinocerebellar degeneration with severe olivopontocerebellar involvement","A Japanese female patient presented with dysarthria and gait disturbance with ataxia at the age of 63. She was initially diagnosed with spinocerebellar degeneration because a head CT showed atrophy of the cerebellum and brainstem, and dilatation of the fourth ventricle. Symptoms including abnormal behavior, dementia, vertical gaze palsy, dysphagia, retrocollis, axial rigidity, grasp reflex and positive Babinski's sign were gradually observed. Tegmental atrophy of the brainstem and dilatation of the third ventricle were apparent on images. The diagnosis was modified to progressive supranuclear palsy (PSP), 6 years after the onset of symptoms. Gastrostomy and tracheotomy were performed 7 and 8 years after onset, respectively, and the patient died one year later. At autopsy the brain weighed 1,030 g and showed atrophy of the frontal lobe and cerebellum. The brainstem was also atrophic, particularly in the tegmentum and pontine base. Neurofibrillary tangles, mainly globose-type, were widespread in the subcortical structure, particularly in the globus pallidus, subthalamic nucleus, nucleus of the oculomotor nerve, substantia nigra, locus ceruleus, pontine nucleus, and the inferior olivary nucleus. Numerous glial fibrillary tangles and argyrophilic threads were also observed particularly in the frontal lobe, basal ganglia, brainstem and cerebellar white matter. The cerebellar dentate nucleus showed neuron loss with grumose degeneration and the Purkinje neuron layer showed neuron loss and Bergmann's gliosis with torpedoes. Tau positive inclusions in the Purkinje neurons, Bergmann glias and dentate nucleus neurons were observed. Pathological findings were consistent with the diagnosis of PSP but the olivopontocerebellar involvement and the quantity of Gallyas-positive/tau-positive structures were generally more severe than in typical PSP cases. According to these clinicopathologic findings and a review of the literature, we speculate on the existence of a PSP subtype with severe olivopontocerebellar involvement that tends to be clinically misdiagnosed as spinocerebellar degeneration.",,"Iwasaki, Y.;Mori, K.;Ito, M.;Mimuro, M.;Yoshida, M.",2011,October,,0,
3657,An autopsy case of senile dementia suspected to be influenced by cerebral amyloid angiopathy with multiple cortical microinfarcts,"A Japanese male showed gradually progressing dementia with psychiatric symptoms including abnormal behavior, night and day reversal, nocturnal delirium, loud shouting, agitation, resistance to care, and loud soliloquy. The patient had a history of right cerebral embolism due to atrial fibrillation 1 month before the onset of dementia Head CT revealed widespread cerebral infarction in the right cerebral hemisphere with bilateral lateral ventricular dilatation. The patient died at the age of 83, 10 months after the onset of cerebral embolism. The clinical diagnosis was mixed-type dementia. On autopsy the brain weighed 1,160 g. Widespread cerebral amyloid angiopathy (CAA) was observed, with distribution most severe in the cerebral cortical vessels and slightly milder in the leptomeningial and subarachnoid vessels. The artery, arteriole, and capillary walls were thickened by the deposition of amorphous, eosinophilic and β-protein immunopositive amyloid. Aβ-deposition was more severe in capillaries and CAA tended to be more severe in the occipital regions. Multiple cortical microinfarcts were found, particularly in the crests of the cerebral gyri of watershed zones. Cerebral white matter, basal ganglia, thalamus, brainstem and spinal cord were relatively preserved from CAA. Infarction was not apparent, except for an embolic lesion in the right cerebral hemisphere and the cortical microinfarcts. We did not observe fibrinoid necrosis, granulomatous angiitis or giant cell reaction associated with CAA-vasculopathies. Rare instances were observed of neurofibrillary tangles and senile plaques corresponding to Braak stages II and A, respectively. We thought the multiple cortical microinfarcts occurred due to chronic hypoperfusion associated with CAA-associated vasculopathies of capillaries in the cerebral cortex. We suspected that the dementia was influenced by the CAA with multiple cortical microinfarcts. Pathologic findings of the patient suggest that CAA without AD-related Aβ-deposition might exist and that capillary Aβ-deposition might be an important factor of hemodynamic perturbation.",amyloid beta protein;aged;agitation;arteriole;article;autopsy;basal ganglion;behavior disorder;brain artery;brain blood vessel;brain embolism;brain infarction;brain stem;brain ventricle dilatation;capillary wall;case report;computer assisted tomography;death;delirium;atrial fibrillation;histopathology;human;human tissue;Japanese (people);male;medical history;protein localization;right hemisphere;senile dementia;senile plaque;spinal cord;thalamus;vascular amyloidosis;white matter,"Iwasaki, Y.;Mori, K.;Ito, M.;Deguchi, A.;Shiraishi, T.;Mimuro, M.;Yoshida, M.;Hashizume, Y.",2010,,,0,
3658,An autopsy case of diffuse neurofibrillary tangles with calcification: Early stage pathologic findings: Case report,"A 66-year-old man with no medically remarkable past or family history gradually showed personality changes, memory disturbance, sleeplessness and abnormal behavior. Neurologic examination showed no focal signs and neither parkinsonism nor cerebellar ataxia was recognized. He died 4 years after the onset of dementia due to chronic renal failure. Neuropathologic examination revealed neuronal loss and gliosis in the temporal cortex, particularly in the subiculum, parahippocampal gyrus and entorhinal cortex, and insular cortex. NFTs were observed to be widespread in the cerebral cortex, especially the temporal cortex and brainstem, while senile plaques were not observed. Gallyas-Braak silver staining revealed the presence of numerous NFTs, glial inclusions and neuropil threads throughout the cerebral neocortex, limbic system, hippocampus and brainstem. The subiculum showed the most severe involvement; severe atrophy, severe neuron loss, and numerous ghost tangles (extracellular NFTs) were apparent. Although NFTs contained both monoclonal anti-3repeat-tau antibody (RD3) and RD4 immunoreactivity, this differed between the intracellular NFTs and ghost tangles. RD3 immunoreactivity was mainly observed in ghost tangles and neuropil threads, whereas RD4 immunoreactivity was mainly observed in intracellular NFTs and glial inclusions. Calcification was also found to be widespread in the cerebral cortex and white matter, basal ganglia, thalamus, cerebellar cortex, white matter and dentate nucleus. These characteristic neuropathologic findings lead to the pathologic diagnosis of diffuse neurofibrillary tangles with calcification (DNTC). It is argued that this patient showed early stage pathologic signs of DNTC due to a short disease duration, which may provide clues regarding the progression of this rare disease. © 2009 Japanese Society of Neuropathology.",creatinine;aged;aphasia;article;ataxia;autopsy;brain stem;calcification;case report;chronic kidney failure;computer assisted tomography;creatinine blood level;dementia;disease course;disease duration;entorhinal cortex;gliosis;hemiparesis;human;immunoreactivity;insomnia;insula;male;memory disorder;neurofibrillary tangle;neurologic examination;nuclear magnetic resonance imaging;parkinsonism;personality disorder;priority journal;senile dementia;subiculum;temporal cortex;urea nitrogen blood level;urine incontinence;white matter,"Iwasaki, Y.;Ito, M.;Mori, K.;Deguchi, A.;Nagaoka, M.;Yoshida, M.;Hashizume, Y.",2009,,,0,
3659,Longitudinal clinical and neuro-radiological findings in a patient with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome),"Since she was 4 years old, the patient had exhibited frequent convulsive seizures, and she experienced severe headaches and depression in adulthood. At the age of 37 years, cerebral calcifications were detected, but she exhibited no cognitive or motor problems. She suffered a cerebral haemorrhage at 49 years old and experienced cognitive dysfunction, dysarthria, dysphagia, and left-hemiparesis as sequelae. After undergoing gastrostomy, she exhibited very slow cognitive deterioration associated with speech disturbance over more than 10 years. She also gradually developed limb spasticity with Babinski signs. Repeated computerised tomography scans revealed unexpected changes including 2 cysts that appeared separately after small haemorrhages, an intracerebral haemorrhage, and intra-cyst bleeding. These longitudinal scans also showed progressive ventricular dilatation and expansion of the leukoencephalopathy, but there were no apparent changes in the intracranial calcifications. Magnetic resonance imaging revealed numerous microbleeds, and magnetic resonance angiography revealed irregularity of the cerebral artery walls with stoppage. Her SNORD118 gene exhibited compound heteromutation of c.38C > G and c.116G > C on different alleles. She was finally diagnosed with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) at the age of 61 years. Past reports have suggested that diffuse cerebral microangiopathy underlies Labrune syndrome's pathogenesis, but we speculate that cerebral macroangiopathy may also underlie it.",analgesic agent;anticonvulsive agent;antidepressant agent;small nucleolar RNA;small nucleolar RNA U8;unclassified drug;adult;allele;anticonvulsant therapy;article;Babinski reflex;brain angiography;brain calcification;brain cyst;brain hemorrhage;case report;cognitive defect;conservative treatment;daily life activity;depression;dysarthria;dysphagia;female;gastrostomy;gene mutation;headache;hemiparesis;human;immobility;leukoencephalopathy;longitudinal study;magnetic resonance angiography;mental deterioration;middle aged;motor dysfunction;neuroimaging;neuroradiology;nuclear magnetic resonance imaging;patient compliance;physical education;priority journal;putaminal hemorrhage;quadriplegia;speech disorder;tonic clonic seizure,"Iwasaki, Y.;Hoshino, K. I.;Mori, K.;Ito, M.;Kawai, Y.;Mimuro, M.;Tsukie, T.;Ikeuchi, T.;Yoshida, M.",2017,,10.1016/j.ensci.2017.07.003,0,
3660,Creutzfeldt-Jakob disease,"This review will explore the clinical and pathological findings of the various forms of Creutzfeldt-Jakob disease (CJD). Clinical findings of CJD are characterized by rapidly progressive cognitive dysfunction, diffusion-weighted magnetic resonance imaging (DWI) hyperintensity, myoclonus, periodic sharp-wave complexes on electroencephalogram and akinetic mutism state. Neuropathologic findings of CJD are characterized by spongiform changes in gray matter, gliosis-particularly hypertrophic astrocytosis-neuropil rarefaction, neuron loss and prion protein (PrP) deposition. The earliest pathological symptom observed by HE staining in the cerebral cortex is spongiform change. This spongiform change begins several months before clinical onset, and is followed by gliosis. Subsequently, neuropil rarefaction appears, followed by neuron loss. Regions showing fine vacuole-type spongiform change reflect synaptic-type PrP deposition and type 1 PrPSc deposition, whereas regions showing large confluent vacuole-type spongiform changes reflect perivacuolar-type PrP deposition and type 2 PrPSc deposition. Hyperintensities of the cerebral gray matter observed in DWI indicate the pathology of the spongiform change in CJD. The cerebral cortical lesions with large confluent vacuoles and type 2 PrPSc show higher brightness and more continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrPSc. CJD cases showing diffuse myelin pallor of cerebral white matter have been described as panencephalopathic-type, and this white matter pathology is mainly due to secondary degeneration caused by cerebral cortical involvement, particularly in regard to neuron loss. In conclusion, clinical and neuroimaging findings and neuropathologic observations are well matched in both typical and atypical cases in CJD. The clinical diagnosis of CJD is relatively easy for typical CJD cases such as the MM1-type. However, even in atypical cases it seems that clinical findings can be used for an accurate diagnosis.",akinetic mutism;astrocytosis;brain cortex lesion;brightness;cell vacuole;cognitive defect;Creutzfeldt Jakob disease;diagnosis;diffusion weighted imaging;electroencephalogram;gene loss;gliosis;gray matter;myoclonus;neuroimaging;neuropil;pallor;pathology;pyramidal sign;staining;synapse;white matter;endogenous compound;myelin;prion protein,"Iwasaki, Y.",2016,,10.1111/neup.12355,0,
3661,"A case of normal pressure hydrocephalus presenting as repeated vertigo, headache and nausea and treated effectively with ventriculoparietal shunt surgery","Normal pressure hydrocephalus (NPH) is a condition involving pathologically enlarged ventricular size with normal opening pressures on lumbar puncture. NPH is associated with a classic triad of dementia, gait disturbance, and urinary incontinence. We report on a patient with NPH presenting with repeated vertigo, headache and nausea. A 21-year-old woman complained of rotatory vertigo, pulsatile headache, nausea and tinnitus in both ears. Brain MRI findings confirmed a diagnosis of hydrocephalus. The cerebrospinal fluid opening pressure was within normal limits. Since then, the patient has continued to experience vertigo, headache and nausea several times a week, and these symptoms were resistant to medical treatments. Results of pure tone audiometry, caloric tests, and vestibular-evoked myogenic potentials were normal in both ears. One year later, she developed gait disturbance and showed vertical macro square wave jerks on a gaze-evoked nystagmus test. A lumbar tap test revealed that removal of cerebrospinal fluid temporally improved her symptoms. She underwent ventriculoparietal shunt surgery, after which she has been symptom-free. Normal results on audio-vestibular examinations and the postsurgical improvement suggested that increased pressure upon the periventricular white matter, including the central vestibular tract, might have been the cause of her symptoms.",adult;anamnesis;article;case report;cerebrospinal fluid;clinical feature;female;headache;human;nausea;neurosurgery;normotensive hydrocephalus;nuclear magnetic resonance imaging;shunting;vertigo,"Iwasaki, S.;Chihara, Y.;Ushio, M.;Sugasawa, K.;Suzuki, M.;Yamasoba, T.;Murofushi, T.",2009,,,0,
3662,Cerebral amyloid angiopathy-related leukodystrophy: A case report,"An 86-year-old woman was admitted following generalized seizure. Postictally she showed disturbance of consciousness, right hemiparesis, and right spatial neglect. Brain fluid attenuated inversion recovery (FLAIR) imaging demonstrated mainly left-sided, but asymmetrical, subcortical white matter lesions. On the second day, level of consciousness improved, along with right hemiparesis and right spatial neglect. Electroencephalography displayed mainly α waves and sporadic θ waves without sharp waves. One week later, however, the patient again experienced somnolence and right hemiparesis. FLAIR revealed day-by-day enlargement of white matter lesions. The possibilities of hypoglycemia, hyperammonemia, hypothyroidism, Hashimoto encephalopathy, collagen disease, antineutrophil cytoplasmic antibody-related angiitis, and infection were excluded based on the results of blood biochemistry and cerebrospinal fluid. We initially suspected intravascular lymphoma, so random skin biopsy was performed, but the results were negative. We then suspected cerebral amyloid angiopathy because of the presence of dementia and multiple microbleeds on T(2)* weighted magnetic resonance imaging. Cerebral biopsy revealed amyloid deposition in cortical arterioles and CD3-positive T cells in the perivascular space. Cerebral amyloid angiopathy-related leukodystrophy was therefore diagnosed and immunosuppressive treatment was started. After 14 days of treatment, clinical symptoms and results of FLAIR imaging were significantly improved. When patients display asymmetrical subcortical white matter lesions with microbleeds on T(2)* weighted imaging, amyloid angiopathy-related inflammation should be considered.",,"Iwanaga, T.;Kaneko, N.;Nishimura, H.;Kimura, K.",2012,August,,0,
3663,Dementia and disability after initial cerebral thrombosis evaluated by MRI and their clinical course,"This study was conducted to clarify the relationship between long-term prognosis of functional status after stroke and the magnetic resonance imaging (MRI) findings as well as complications in the course. A total of 98 patients with initial cerebral thrombosis were enrolled, and 65 patients surviving 5 years after the event, were studied in terms of cognitive function and activity of daily living (ADL). Mean age at registration (3 months after the event) was 72.0 years-old and 44 were male. MRI findings were divided into eight categories including the size and laterality of infarction, in addition to six categories as previously described. The presence of dementia was identified according to the HDS-R and the DSM-III-R scales, and the extent of dementia, assessed with the CDR scale, was divided into 3 grades: none, mild, and severe. The extent of ADL status was also graded into 3 classes: independent, partially dependent, and completely dependent. Recurrence of stroke, pneumonia, and motor disorders (hip joint fracture) were counted as complications during the course. At baseline, dementia was identified in 44, consisting of 30 mild and 14 severe dementias. During 5 years, 11 cases with mild dementia showed deterioration, and 1 case without dementia developed mild dementia. At registration, there were 46 cases with partially dependent ADL status and 22 cases completely dependent, while deterioration of ADL was seen in 17 during 5 years. Multiple regression analyses showed that diffuse PVH and pneumonia were contributory factors to the development of dementia, while dementia, pneumonia and motor disorders were risk factors for deterioration of ADL. These findings suggested that in patients with cerebral thrombosis, especially in patients with diffuse PVH, pneumonia and motor disorders should be taken care of in order to prevent functional decline.","Activities of Daily Living;Aged;Aged, 80 and over;Dementia, Vascular/complications/ diagnosis/ physiopathology;Female;Humans;Intracranial Thrombosis/ complications;Magnetic Resonance Imaging;Male;Prognosis","Iwamoto, T.;Shimizu, T.;Ami, M.;Yoneda, Y.;Imamura, T.;Takasaki, M.",2000,Feb,,0,
3664,[Long-term prognosis of patients with initial cerebral thrombosis and the MRI findings],"To clarify the relationship between long-term prognosis of patients with stroke and their MRI findings, 103 patients with initial cerebral thrombosis, who survived more than three months after the ictus, were studied for five years. The mean age of 98 patients (T group), who were followed up completely, was 73.1 years-old and 65 were men. The age-matched controls consisted of two groups: 65 subjects, who had hypertension and/or diabetes without a history of stroke (R group), and 85 subjects, who had any hypertension, diabetes and stroke (N group). MRI findings were divided into six categories: 1) types of causative lesion, 2) grades of periventricular hyperintensity (none, rims/caps, patchy, diffuse PVH), 3) number of spotty lesions, 4) presence of silent infarction. 5) ventricular dilatation, and 6) extents of brain atrophy. Types of causative lesion were subdivided into 3 subtypes; infarction of the perforating artery territory (P type), infarction of the cortical artery territory (C type), and brainstem infarction (B type). The presence of vascular risks and dementia, and the extent of activity of daily living (ADL) were assessed. The P, C, and B types were identified by MRI in 46, 36, and 16 of the T group, respectively. Motor impairment, dementia, and an ADL status of complete dependence at discharge were also seen in 84, 44, and 22, respectively. In the T group, 33 patients died during five years, which resulted in a cumulative mortality rate of 33.7% and an annual mortality rate of 8.2%. Based on log-rank analysis, the survival rate of the T group revealed was significantly lower than those of the R and N groups. The recurrent rate in the T group (annual stroke recurrence rate was 4.0%) was higher than in the R and N groups, but stroke recurrence was not the cause of death and two thirds of deaths were due to aspiration pneumonia and/or asphyxia. Cox hazard regression analysis for death due to respiratory diseases showed that the hazard ratios of infarction, patchy PVH, and more than 4 spotty lesions were 8.87 (p < .001), 0.31 (p = .058), and 0.44 (p = .098), respectively. Compared to the survival group, rates of complete dependence in ADL, dementia, and brain atrophy were significantly higher in the death group with low incidences of the P type and patchy PVH, which indicated small vessel disease. These findings suggested that in patients with cerebral thrombosis, even in the chronic phase, care should be taken to prevent pneumonia and/or asphyxia due to bulbar palsy. Furthermore, no MRI findings were distinct predictors of long-term prognosis, although infarction based on the small vessel disease had rather good outcome in terms of respiratory disease.","Aged;Aged, 80 and over;Brain/pathology;Female;Humans;Intracranial Embolism and Thrombosis/*diagnosis;*Magnetic Resonance Imaging;Male;Middle Aged;Prognosis","Iwamoto, T.;Shimizu, T.;Akazawa, M.;Kikawada, M.;Nishimura, T.;Takasaki, M.",1999,Feb,,0,
3665,"Brain MRI findings in patients with initial cerebral thrombosis and the relationship between incidental findings, aging and dementia","To estimate the relationship between aging, dementia and changes observed on magnetic resonance imaging (MRI) seen in elderly patients with cerebral thrombosis, MRI findings in 103 patients with an initial stroke event (thrombosis group) were compared with those of 37 patients with hypertension/diabetes (high risk group) and 78 patients without those disorders (low risk group). In addition to the causative lesions in the thrombosis group, periventricular hyperintensities (PVH), spotty lesions (SL), silent infarctions (SI), ventricular dilatation (VD), and cortical atrophy (CA) were analyzed in these groups. Infarctions located in the internal capsule/corona radiata were the most frequent causative lesion. Compared to the low risk group, a high incidence of patchy/diffuse PVH, SI, and severe CA was seen in both the thrombosis group and the high risk group. Widespread PVH and multiple SL increased with age in the thrombosis group, while severe CA was seen in each group. SI and VD tended to increase after age 60, though they were not significant. Dementia, diagnosed in 40 out of 78 patients, increased with age. Multivariate analysis revealed the degree of the effects of MRI findings on dementia to be marked in PVH, brain atrophy, causative lesions, and SL, in that order. These results indicated that diffuse PVH and brain atrophy, developing with age, promoted dementia in the elderly with vascular lesions. Moreover, they suggested that a variety of silent brain lesions recognized on MRI other than infarction can affect symptoms in the elderly.",,"Iwamoto, T.;Okada, T.;Ogawa, K.;Yanagawa, K.;Uno, M.;Takasaki, M.",1994,1994,,0,
3666,"[Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome]","To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n = 33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n = 69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function.","Adult;Aged;Brain/*radiography;Cerebral Infarction/*complications;Deglutition Disorders/*diagnosis/etiology;Female;Humans;Male;Middle Aged;Point-of-Care Systems;*Tomography, X-Ray Computed","Iwamoto, T.;Koshibu, J.;Kikawada, M.;Yoneda, Y.;Uno, M.;Takasaki, M.;Imamura, T.",2001,Sep,,0,
3667,[Clinical study on the relationship between middle cerebral artery lesions and Binswanger type infarction],"To investigate the relationship between middle cerebral artery (MCA) trunk lesions and the etiology of Binswanger type (B type) infarction, which was demonstrated as a diffuse subcortical low density area/high intensity area by CT/MRI, patients with both MCA lesions and B type infarction were studied clinically. Eighteen patients with B type infarction were diagnosed among 224 patients with MCA occlusion/stenosis on angiography accounting for 8%. The incidence was as high as 25% in M2 stenosis. The mean age of B type infarction patients was 64 years and 16 of them were men. Chronologically stepwize/slowly-progressive deterioration of clinical manifestations were observed in 14. All patients had hemiplegia, though half of them were mild or moderate in severity. Furthermore, aphasia, Gerstmann syndrome and dementia were present in 10, 1 and 2 patients, respectively. Twelve had a history of hypertension, while 11 showed transient decreases with marked changes (more than 31 mmHg in mean arterial blood pressure) in arterial blood pressure during their clinical course. Out of 9 patients in whom cerebral blood flow (CBF) was measured by 133Xe injection method/inhalation method, 7 demonstrated mild to moderate decreases in mean CBF (more than 30 ml/100 g/min) with no relation to the severity of MCA lesions. These findings suggested that hemodynamic mechanisms associated with hypoperfusion due to marked fluctuations in blood pressure are accelerating factors of B type infarction and MCA lesions, even though ischemia in the subcortical area due to leptomeningeal anastomosis may be mild or moderate.","Aged;Arterial Occlusive Diseases/complications/physiopathology;Blood Pressure;Cerebral Arterial Diseases/*complications/physiopathology;Cerebral Infarction/*etiology/physiopathology;Cerebrovascular Circulation;Constriction, Pathologic/complications/physiopathology;Female;Humans;Male;Middle Aged","Iwamoto, T.;Hatano, N.;Takagi, T.;Katsunuma, H.;Ishihara, N.",1989,Jul,,0,
3668,Combined treatment of methylprednisolone pulse and memantine hydrochloride prompts recovery from neurological dysfunction and cerebral hypoperfusion in carbon monoxide poisoning: A case report,"A 49-year-old healthy man developed sudden unconsciousness under inadequate ventilation. Blood gas analysis showed carboxyhemoglobin of 7.3%. After normobaric oxygen therapy, he recovered completely 7 days later. At 3 weeks after carbon monoxide (CO) exposures, memory and gait disturbances appeared. Neurological examination revealed Mini-Mental State Examination (MMSE) score of 5 of 30 points, leg hyper-reflexia with Babinski signs, and Parkinsonism. Brain fluid-attenuated inversion recovery imaging disclosed symmetric hypointense lesions in the thalamus and the globus pallidus, and hyperintense lesions in the cerebral white matter. Brain single-photon emission tomography (SPECT) scanning with (99m)Technesium-ethyl cysteinate dimer displayed marked hypoperfusion in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. He was diagnosed as CO poisoning and treated with hyperbaric oxygen therapy. The neurological deficits were not ameliorated. At 9 weeks after neurological onset, methylprednisolone (1000 mg/day, intravenous, 3 days) and memantine hydrochloride (20 mg/day, per os) were administered. Three days later, MMSE score was increased from 3 to 20 points. Neurological examination was normal 3 weeks later. Brain SPECT exhibited 20% increase of regional cerebral blood flows in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. These clinicoradiological changes supported that the treatment with steroid pulse and memantine hydrochloride could prompt recovery from neurological dysfunction and cerebral hypoperfusion. Further clinical trials are warranted whether such combined therapy can attenuate neurological deficits and cerebral hypoperfusion in patients with CO poisoning. © 2014 by National Stroke Association.",,"Iwamoto, K.;Ikeda, K.;Mizumura, S.;Tachiki, K.;Yanagihashi, M.;Iwasaki, Y.",2014,March,,0,
3669,"Autosomal recessive hereditary cortical cerebellar atrophy with striatal degeneration. Two siblings showing choreoathetoid movement, ataxia, dementia, and amenorrhea","We present two siblings with hereditary cortical cerebellar atrophy (CCA), who showed peculiar clinical features. Their unaffected parents are cousins. The mode of inheritance in this family was autosomal recessive. Both patients developed involuntary movement and ataxia during the fourth decade. The proband (patient 1) was the elder sister. She developed choreoathetoid involuntary movement and cerebellar ataxia at the age of 32. At the age of 39, she showed mental deterioration and marked gait disturbance due to severe ataxia and amyotrophy. At the age of 40, she took medication for hypertension. At the age of 42, she was bedridden and had generalized convulsions and dysautonomia. Involuntary movement continued until her death at age 44. She had amenorrhea since the age of 25 years. Neuropathological findings. The brain weighed 1,010 g. We found marked degeneration in the cerebellar cortex including the molecular, Purkinje cells, and granular cell layers, and in the inferior olivary nuclei. In the basal ganglia, the putamen and caudate nuclei were moderately affected, but the substantia nigra and globus pallidus were spared. The cerebral cortex was spared, but the cerebral white matter showed diffuse myelin pallor without fibrillary gliosis. In the pons, the volume of the tegmentum was moderately decreased, but the base was spared. The spinal cord was normal. The findings of the patient differed from those of the case originally reported by Gordon Holmes in 1907. Holmes autopsied a case showing severe degeneration in both the cerebellar cortex including all three layers and the inferior olivary nucleus as in our patient. However, the striatum of his case spared and the patient did not develop involuntary movement as did other patients. The patients presented here should be distinguished from Holmes' original case clinicopathologically. Patient 2 was the younger sister of the patient 1. She had mild mentally retardation. She had amenorrhea since the age of 26. She developed athetoid movements in the trunk and upper extremities at the age of 36. We examined her at the age of 42. She showed choreoathetoid movement and increased deep tendon reflexes prominent in the lower extremities. Although cerebellar ataxia was obscure, computed tomography of the brain showed moderate cerebellar atrophy. The clinicopathological findings were identical with those of the cases reported by Nakayama et al in 1975. They diagnosed their cases as Holmes type of cortical cerebellar atrophy with the putaminal degeneration. However, the findings in their cases and the present patients are quite different from those of Holmes' original cases. We think the findings of the present patients and Nakayama's case might reflect a new spinocerebellar degenerative disease.",adult;amenorrhea;article;ataxia;brain atrophy;case report;cerebellum cortex;chorea;computer assisted tomography;female;human;neuropathology,"Iwabuchi, K.;Nakazawa, Y.;Akai, J.;Yagishita, S.;Amano, N.",1994,,,0,
3670,Progressive leukoencephalopathy associated with aluminum deposits in myelin sheath,"A 20-year-old woman with progressive leukoencephalopathy developed mental and motor disabilities and fell into a coma after suffering head trauma and febrile episodes from infancy. Brain imaging showed massive abnormal signals in the white matter. The electron spectroscopic imaging of biopsied brain tissue confirmed the electron-dense deposits to be associated with aluminum accumulation in the myelin sheath. Her brain pathology, which showed ferritin- and naphtochrome green-positive deposits, supported the imaging analysis. The clinicopathological features indicate a new form of progressive leukoencephalopathy. © 2008 Sage Publications.",,"Itoh, M.;Suzuki, Y.;Sugai, K.;Ozuka, N.;Ohsawa, M.;Otsuki, T.;Goto, Y.",2008,August,,0,
3671,Relapsing polychondritis with an intracranial granuloma: A case report,"We report a case of relapsing polychondritis (RP) with an intracranial granuloma. A 67-year-old man developed progressive disorientation during the course of RP with left auricular chondritis and episcleritis. He had history of sinusitis and rupture of an aneurysm in middle cerebral artery. Laboratory examinations revealed high erythrocyte sedimentation rate and positive C-reactive protein. Head CT and MRI with contrast enhancement showed a mass adjacent to the falx cerebri and lesions in the frontal skull base. The mass was surrounded by extensive perifocal edema that spread mainly into the frontal white matter on both sides. Histologically, the mass displayed an inflammatory granuloma. By removal of the mass, edema decreaed around the granuloma, and his disorientation improved markedly. Surgical findings revealed the granuloma was separated from sinusitis. There are a few reports on RP with an intracranial granuloma.",C reactive protein;aged;aneurysm rupture;article;brain artery aneurysm;brain edema;case report;clinical feature;computer assisted tomography;contrast enhancement;dementia;disease course;disorientation;episcleritis;erythrocyte sedimentation rate;external ear;frontal lobe;granuloma;histopathology;human;human tissue;inflammation;laboratory test;male;middle cerebral artery;neuroimaging;neurosurgery;nuclear magnetic resonance imaging;polychondritis;recurrent disease;sinusitis;skull base;treatment outcome;white matter,"Itoh, M.;Miura, H.;Shimamura, H.;Kubodera, T.;Matsuoka, T.",2004,,,0,
3672,A case report of Binswanger type encephalopathy manifested after coronary artery bypass grafting,"A 68-year-old man showed signs of dementia after undergoing triple CABG with cardiopulmonary bypass. Brain CT revealed widespread atrophy and lucency in white matter without any sign of stroke. No critical stenosis in cervical vessels was found in duplex scanning. He kept politeness well, but had severe memory impairment. These findings were characteristic of Binswanger type encephalopathy which must have been latent preoperatively. This disease is caused by ischemic damage in brain stem and white matter due mainly to atherosclerotic micro cerebrovasculopathy, and highly related to hypertension. We have to be aware of intracranial cerebrovascular disease when assessing the risk of brain damage in candidates for CABG.",aged;arteriosclerosis;article;brain ischemia;brain stem;cardiopulmonary bypass;case report;coronary artery bypass graft;human;hypertension;male;multiinfarct dementia;risk assessment;vascularization,"Ito, T.;Hagiwara, H.;Takemura, H.;Maekawa, A.;Akita, T.;Yano, Y.;Abe, T.",2000,,,0,
3673,Massive accumulation of 11C-Pittsburg compound B in the occipital lobes of a patient with early-onset dementia accompanied by muscle weakness and hypertonicity,"A 44-year-old woman underwent 11C-Pittsburg compound B (11C-PiB), 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), 99mTc-ethyl-cysteinate-dimer single photon emission computed tomography, and magnetic resonance imaging after presenting with progressive dementia, muscle weakness, and hypertonicity. Some of her family members had died of muscle weakness with early-onset dementia of unknown etiology. Neurological and psychological examinations revealed moderate dementia in general fields and muscle weakness in her upper limbs. 11C-PiB PET/CT revealed abnormal accumulations of amyloid in the bilateral occipital lobes, while physiological uptakes of 11C-PiB in areas that normally show high uptake, such as white matter, appeared relatively decreased. Meanwhile, cerebrospinal fluid (CSF) amyloid-β was decreased, and CSF total and phosphorylated tau proteins were increased. This case may be representative of a new category of amyloid deposition disease characterized by early-onset dementia, muscle weakness, and hypertonicity, or at least, a new uptake pattern of PiB in variant AD. © 2013 The Japanese Society of Nuclear Medicine.",,"Ito, K.;Sano, T.;Kamiya, K.;Nakata, Y.;Shigemoto, Y.;Sato, N.;Oya, Y.;Matsuda, H.",2013,December,,0,
3674,Imaging of amyloid deposition in human brain using positron emission tomography and 18F FACT: comparison with 11C PIB,"PURPOSE: The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The (18)F-labeled amyloid tracer, [(18)F]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-y l)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [(11)C]Pittsburgh compound B (PIB) and [(18)F]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared. METHODS: Two PET scans, one of each with [(11)C]PIB and [(18)F]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation. RESULTS: No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [(18)F]FACT studies without partial volume correction, while significant differences were observed in [(11)C]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [(18)F]FACT studies as well as [(11)C]PIB. Relatively lower uptakes of [(11)C]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [(18)F]FACT. Relatively higher uptake of [(11)C]PIB in distribution was observed in the frontal and parietal cortices. CONCLUSION: Since [(18)F]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [(11)C]PIB and [(18)F]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the autoradiographic and histochemical assays of postmortem AD brain sections.","Aged;Aged, 80 and over;Alzheimer Disease/ radionuclide imaging;Benzothiazoles/pharmacokinetics;Benzoxazoles/pharmacology;Brain/pathology/ radionuclide imaging;Case-Control Studies;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/ radionuclide imaging;Plaque, Amyloid/ radionuclide imaging;Positron-Emission Tomography;Radiopharmaceuticals/pharmacokinetics;Thiazoles/pharmacology;Tissue Distribution","Ito, H.;Shinotoh, H.;Shimada, H.;Miyoshi, M.;Yanai, K.;Okamura, N.;Takano, H.;Takahashi, H.;Arakawa, R.;Kodaka, F.;Ono, M.;Eguchi, Y.;Higuchi, M.;Fukumura, T.;Suhara, T.",2014,Apr,10.1007/s00259-013-2620-7,0,
3675,Quantitative analysis of amyloid deposition in Alzheimer disease using PET and the radiotracer(11)C-AZD2184,"Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tertbutyl(dimethyl) silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated. Methods: After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed. Results: Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, DVR values in the centrum semiovale were more than 1 for both control subjects and AD patients, suggesting binding to myelin. The standardized uptake value ratio calculated from integrated time-activity curves in brain regions and the reference region was statistically in good agreement with DVR. Conclusion: Although the white matter binding of (11)C-AZD2184 may have some effect on cortical measurement, it can be concluded that the kinetic behavior of (11)C-AZD2184 is suitable for quantitative analysis. The standardized uptake value ratio can be used as a validated measure of (11)C-AZD2184 binding in clinical examinations without arterial input function. COPYRIGHT © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",,"Ito, H.;Shimada, H.;Shinotoh, H.;Takano, H.;Sasaki, T.;Nogami, T.;Suzuki, M.;Nagashima, T.;Takahata, K.;Seki, C.;Kodaka, F.;Eguchi, Y.;Fujiwara, H.;Kimura, Y.;Hirano, S.;Ikoma, Y.;Higuchi, M.;Kawamura, K.;Fukumura, T.;Lindström B̈̈oo, É;Farde, L.;Suhara, T.",2014,1,,0,
3676,Notch3 gene polymorphism and ischaemic cerebrovascular disease,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a type of hereditary stroke and dementia. More than 90% of patients with CADASIL have mutations in the Notch3 gene. All mutations either create or destroy a cysteine residue in the epidermal growth factor-like repeats. In addition, five polymorphisms, which lead to amino acid substitutions, have been identified within the Notch3 coding sequence. However, whether these polymorphisms affect Notch signalling or are involved in cerebrovascular diseases is unknown. In the present study, we investigated a possible association between a T6746C polymorphism in the Notch3 coding region and the occurrence of symptomatic ischaemic cerebrovascular disease (CVD) was investigated. Two hundred and thirty five patients with CVD, as confirmed by brain CT or MRI, and 315 age and sex matched control subjects were analyzed for genotype frequencies of the T6746C polymorphism in Notch3. The genotype distributions were: patients with CVD, C/C 14.0%, C/T 45.5%, and T/T 40.4%; controls, C/C, 14.3%; C/T, 47.9%; T/T, 37.8%. The Japanese population has a higher C allele frequency of the T6746C polymorphism than European populations. There was no significant difference between the T6746C polymorphism in patients with CVD and controls (chi(2)=0.414, p=0.813). This was confirmed by the results of multiple logistic regression analysis including established risk factors (chi(2) =4.65, p=0.311). In conclusion, the results indicate that T6746C polymorphism in the intracellular domain of the Notch3 gene is not associated with an increased risk for CVD.","Aged;Amino Acid Substitution/genetics;Cerebral Infarction/*genetics;Chromosome Aberrations;Dementia, Multi-Infarct/*genetics;Female;Gene Frequency;Genes, Dominant;Humans;Ischemic Attack, Transient/*genetics;Male;Middle Aged;Polymorphism, Genetic/*genetics;Proto-Oncogene Proteins/*genetics;*Receptors, Cell Surface;Receptors, Notch;Risk;Signal Transduction/genetics","Ito, D.;Tanahashi, N.;Murata, M.;Sato, H.;Saito, I.;Watanabe, K.;Fukuuchi, Y.",2002,Mar,,0,
3677,Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies,"Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies. © 2014 Wiley Periodicals, Inc.",,"Ithapu, V.;Singh, V.;Lindner, C.;Austin, B. P.;Hinrichs, C.;Carlsson, C. M.;Bendlin, B. B.;Johnson, S. C.",2014,August,,0,
3678,Demographic Features and Neuropsychological Correlates in a Cohort of 200 Patients with Vascular Cognitive Decline Due to Cerebral Small Vessel Disease,"INTRODUCTION: Vascular dementia is the second most common form of dementia and is potentially reversible. Small vessel disease (SVD) closely mimics degenerative dementia in view of its sub-acute onset and progressive course. Therefore, unlike large vessel disease, Hachinski Ischemic scale score may not always reflect vascular cognitive decline resulting in diagnostic and therapeutic confusions. Therefore, there is a need for detailed neuropsychological assessment for various cognitive domains for early identification of vascular cognitive decline as it carries a very good long term prognosis for cognitive morbidity, unlike degenerative dementias. PATIENTS AND METHODS: This prospective study involves thorough domain based neuropsychological assessment of patients with a radiological diagnosis of SVD involving the following parameters-digit forward and backward, category fluency, color trails, stick test, logical memory test, and bender gestalt test. Magnetic resonance imaging scans done using 3-tesla machines and SVD graded using Fazekas visual scale. RESULTS: The mean Hachinskis score was less sensitive for differentiating vascular dementia from degenerative dementia. However, the domain based neuropsychological scores were highly sensitive showing statistically significant impairment in all 6 domains tested and compared with Fazekas 1-3 grades in imaging. DISCUSSION AND CONCLUSION: This study aimed at establishing an early diagnosis of vascular mild cognitive impairment using domain wise neuropsychological testing and correlating it with radiological scores. Hachinskis score is more sensitive for large vessel disease in view of acute onset and step-like progression as against steady progression in SVD. However, domain-wise testing was highly sensitive in identifying early cognitive impairment in patients with SVD, and early therapeutic interventions are highly rewarding.",,"Issac, T. G.;Chandra, S. R.;Rajeswaran, J.;Christopher, R.;Philip, M.",2016,Mar-Apr,10.4103/0253-7176.178778,0,
3679,Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited systemic vascular disorder characterized by recurrent subcortical ischemic strokes leading to vascular dementia. The gold standard to confirm the diagnosis is to identify a mutation in the underlying gene NOTCH3, encoding a transmembrane receptor protein. Granular osmiophilic material (GOM) deposition around vascular smooth muscle cells is a specific diagnostic feature of CADASIL and electron microscopic examination of a skin biopsy is another useful method for its diagnosis. Although accumulation of Notch3 ectodomain on the surface of vascular smooth muscle cells has been reported, the composition of GOM has not been elucidated. To elucidate the relationship between Notch3 protein and GOM, we performed postembedding immunogold electron microscopy using cryofixed and freeze substituted skin taken from two CADASIL patients. Our results demonstrate that GOM around vascular smooth muscle cells was specifically labeled with antibodies against the extracellular portion of Notch3 but not with antibodies recognizing the intracellular Notch3 domain. In non-CADASIL skin sections, no antibody binding was detected around the small dermal arteries. From these results, the major component of GOM in CADASIL patients is the ectodomain of the Notch3 gene product. Our results shed light on the relationship between Notch3 gene mutations and morphological deposition of GOM around the vascular smooth muscle cells. © Springer-Verlag 2006.",cysteine;glycine;membrane protein;Notch3 receptor;adult;amino acid substitution;antigen binding;article;CADASIL;case report;cell granule;cell labeling;cerebrovascular accident;cryopreservation;dizziness;electron microscopy;gene mutation;gold standard;human;human cell;human tissue;immunogold electron microscopy;male;multiinfarct dementia;nuclear magnetic resonance imaging;point mutation;priority journal;protein domain;sensitivity and specificity;skin biopsy;skin blood vessel;smooth muscle fiber;tinnitus;vascular smooth muscle,"Ishiko, A.;Shimizu, A.;Nagata, E.;Takahashi, K.;Tabira, T.;Suzuki, N.",2006,,,0,
3680,"Cerebral autosomal dominant arteriopathy with subcortical lnfarcts and leukoencephaloapthy (CADASIL): A hereditary cerebrovascular disease, which can be diagnosed by skin biopsy electron microscopy","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease characterized by recurrent subcortical ischemic strokes starting in the third or fourth decade as a result of mutations in the Notch3 gene. Granular osmiophilic material (GOM) deposition around the vascular smooth muscle cells is a specific feature and electron microscopic observations of skin biopsies are useful for this diagnosis. A 39-year-old female with dizziness, abnormal visual fields, and hemiplegia, and a 42-year-old male with tinnitus and dizziness, were suspected of suffering from CADASIL based on MRI findings. Both cases were shown to have characteristic deposits of GOM, 200 to 800 nm in diameter, around the vascular smooth muscle cells of small arteries in the deep dermis, and thus the diagnoses of CADASIL were made, although there was no family history of cerebrovascular disorders or dementia. Dermatologists should be aware of these ultra-structural findings because this disease may occur sporadically and might be more common than initially thought. Copyright © 2005 by Lippincott Williams & Wilkins.",Notch3 receptor;adult;article;CADASIL;case report;cerebrovascular disease;clinical feature;dizziness;electron microscopy;family history;female;gene mutation;hemiplegia;human;human cell;human tissue;male;nuclear magnetic resonance imaging;priority journal;skin biopsy;tinnitus;vascular smooth muscle;visual field defect,"Ishiko, A.;Shimizu, A.;Nagata, E.;Ohta, K.;Tanaka, M.",2005,,,0,
3681,Relationship between tissue Doppler measurements of left ventricular diastolic function and silent brain infarction in patients with non-valvular atrial fibrillation,"Aims: Left ventricular (LV) diastolic function assessed by tissue Doppler imaging (TDI) is reported to be associated with left atrial (LA) blood stasis in patients with non-valvular atrial fibrillation (AF). This study aimed to evaluate the relationship of diastolic TDI parameters with silent brain infarction (SBI) on brain magnetic resonance imaging (MRI), and in turn the risks of subsequent stroke or dementia, in non-valvular AF patients. Methods and results: The study population consisted of 171 neurologically asymptomatic patients with non-valvular AF who underwent transoesophageal echocardiography (TOE) (128 men; mean age, 63 +/- 11 years). We measured diastolic TDI parameters by transthoracic echocardiography, and also screened for SBI employing brain MRI. Early transmitral flow velocity (E) and mitral annular velocity by TDI (e') were measured, and E/e' ratios were calculated. An increased tertile of the E/e' ratio was significantly related to high prevalences of LA abnormalities detected by TOE (32% vs. 12% vs. 9%; P =0.002) and SBI on brain MRI (46% vs. 23% vs. 14%; P < 0.001). In multivariate logistic regression analyses after adjustment for age, hypertension, chronic kidney disease, and CHA2DS2-VASc score >/=2, the E/e' ratio >/=12.4 was found to be an independent predictor of the presence of SBI (OR 3.98, 95% CI 1.74-9.07; P = 0.001). Conclusions: Impaired LV diastolic function evaluated by increased E/e' ratio was closely associated with the presence of SBI independent of CHA2DS2-VASc score. TDI measurements are non-invasive and useful for risk stratification of the early stage of cerebral damages in patients with non-valvular AF.",atrial fibrillation;echocardiography;silent brain infarction;tissue Doppler imaging,"Ishikawa, S.;Sugioka, K.;Sakamoto, S.;Fujita, S.;Ito, A.;Norioka, N.;Iwata, S.;Nakagawa, M.;Takagi, M.;Miki, Y.;Ueda, M.;Yoshiyama, M.",2017,Nov 1,,0,3682
3682,Relationship between tissue Doppler measurements of left ventricular diastolic function and silent brain infarction in patients with non-valvular atrial fibrillation,"AIMS: Left ventricular (LV) diastolic function assessed by tissue Doppler imaging (TDI) is reported to be associated with left atrial (LA) blood stasis in patients with non-valvular atrial fibrillation (AF). This study aimed to evaluate the relationship of diastolic TDI parameters with silent brain infarction (SBI) on brain magnetic resonance imaging (MRI), and in turn the risks of subsequent stroke or dementia, in non-valvular AF patients. METHODS AND RESULTS: The study population consisted of 171 neurologically asymptomatic patients with non-valvular AF who underwent transoesophageal echocardiography (TOE) (128 men; mean age, 63 +/- 11 years). We measured diastolic TDI parameters by transthoracic echocardiography, and also screened for SBI employing brain MRI. Early transmitral flow velocity (E) and mitral annular velocity by TDI (e') were measured, and E/e' ratios were calculated. An increased tertile of the E/e' ratio was significantly related to high prevalences of LA abnormalities detected by TOE (32% vs. 12% vs. 9%; P =0.002) and SBI on brain MRI (46% vs. 23% vs. 14%; P < 0.001). In multivariate logistic regression analyses after adjustment for age, hypertension, chronic kidney disease, and CHA2DS2-VASc score >/=2, the E/e' ratio >/=12.4 was found to be an independent predictor of the presence of SBI (OR 3.98, 95% CI 1.74-9.07; P = 0.001). CONCLUSIONS: Impaired LV diastolic function evaluated by increased E/e' ratio was closely associated with the presence of SBI independent of CHA2DS2-VASc score. TDI measurements are non-invasive and useful for risk stratification of the early stage of cerebral damages in patients with non-valvular AF.",atrial fibrillation;echocardiography;silent brain infarction;tissue Doppler imaging,"Ishikawa, S.;Sugioka, K.;Sakamoto, S.;Fujita, S.;Ito, A.;Norioka, N.;Iwata, S.;Nakagawa, M.;Takagi, M.;Miki, Y.;Ueda, M.;Yoshiyama, M.",2016,Dec 29,,0,
3683,Dilated Perivascular Spaces in the Centrum Semiovale Begin to Develop in Middle Age,"BACKGROUND: Dilated perivascular spaces in the centrum semiovale (CSO-PVS) are closely related to small vessel disease. However, recent studies have revealed that cerebral amyloid angiopathy can cause dilation of the CSO-PVS and obstruction of interstitial fluid flow along the intramural periarterial drainage. OBJECTIVE: To examine the severity and age-related prevalence of CSO-PVS through magnetic resonance imaging (MRI) and investigate their clinically relevant factors. METHODS: This study included 1,060 subjects who participated in our brain program. The subjects ranged from 23 to 83 years in age and were active in society. The frequencies of the MRI abnormalities of small vessel diseases, including CSO-PVS, were examined. The CSO-PVS severity was classified into three grades: G0, G1, G2, according to the visual rating. The subjects were divided into five age groups and their age-related frequencies were also studied. Using the clinico-laboratory data of 712 subjects, the clinically relevant factors of CSO-PVS were investigated using logistic regression analysis. RESULTS: The frequencies of all G0 (""normal"") MRI abnormalities significantly decreased with age. A high prevalence of G2 CSO-PVS was observed (24%) in the youngest group aged</=39 years, whereas other MRI abnormalities in this group were not or rarely observed. In multivariable logistic regression analyses, G2 CSO-PVS was found to be closely associated with age, hypertension, and the estimated glomerular filtration ratio. CONCLUSIONS: This study reveals that CSO-PVS begin to develop in subjects aged less than 39 years. Age-related changes are involved. Further studies are necessary to elucidate the pathophysiological role of the CSO-PVS.",Aging;cerebral amyloid angiopathy;dementia;interstitial fluid;magnetic resonance imaging;small vessel disease;white matter,"Ishikawa, M.;Yamada, S.;Yamamoto, K.",2018,,,0,
3684,Three-dimensional observation of Virchow-Robin spaces in the basal ganglia and white matter and their relevance to idiopathic normal pressure hydrocephalus,"Background: Virchow-Robin spaces (VRS) are brain perivascular spaces containing perforating arteries. Although enlarged VRS are associated with various disorders such as Alzheimer's disease, cerebrovascular disease, and head trauma, their functional role remains unclear. Using highly fluid-sensitive magnetic resonance imaging (MRI) sequences, fine morphological features of VRS and their relevance to idiopathic normal pressure hydrocephalus (iNPH) were investigated. Methods: Three-dimensional constructive interference in steady state (3D-CISS) on 3 Tesla MRI was applied to 29 individuals. The morphology and number of VRS in the basal ganglia and white matter were compared between 20 patients with iNPH and nine age-matched controls. The VRS number per hemisphere was classified into three grades: few, moderate, and abundant. Results: Virchow-Robin spaces in the basal ganglia were curved, irregularly sized and shaped, and communicated with the cerebrospinal fluid in the subarachnoid space; they contained perforating arteries. VRS in the white matter were straight, smooth, homogeneously sized and shaped, and did not penetrate the cortex. Arteries were not seen in VRS of the white matter. White matter VRS were sparse in patients with iNPH. In contrast, basal ganglia VRS positively correlated with age. Postoperatively after shunt surgery, VRS in the white matter were mildly decreased in diameter, but not in number. No significant changes were noted in basal ganglia VRS. Conclusions: The present study revealed different morphological features of VRS in the basal ganglia and white matter. VRS in the basal ganglia were seen as genuine perivascular spaces; while neither communication with subarachnoid spaces nor arteries were seen in white matter VRS, even by 3D-CISS sequences and high-resolution magnetic resonance angiography on 3T-MRI. White matter VRS were sparse in patients with iNPH and they were mildly decreased in diameter, but did not change in number after surgery. At present, it remains unclear whether the white matter VRS are dilated interstitial fluid spaces or cerebral amyloid angiopathy, or both. Further studies are necessary to elucidate the functional role of VRS in normal subjects and patients with iNPH.",Alzheimer disease;artery;basal ganglion;brain;cerebrospinal fluid;cerebrovascular disease;diseases;head injury;hemisphere;human;interpersonal communication;interstitial fluid;liquid;magnetic resonance angiography;morphology;normal human;normotensive hydrocephalus;nuclear magnetic resonance imaging;patient;steady state;subarachnoid space;surgery;vascular amyloidosis;white matter,"Ishikawa, M.;Yamada, S.;Yamamoto, K.",2015,,10.1186/s12987-015-0010-1,0,
3685,Three-dimensional observation of Virchow-Robin spaces in the basal ganglia and white matter and their relevance to idiopathic normal pressure hydrocephalus,"BACKGROUND: Virchow-Robin spaces (VRS) are brain perivascular spaces containing perforating arteries. Although enlarged VRS are associated with various disorders such as Alzheimer's disease, cerebrovascular disease, and head trauma, their functional role remains unclear. Using highly fluid-sensitive magnetic resonance imaging (MRI) sequences, fine morphological features of VRS and their relevance to idiopathic normal pressure hydrocephalus (iNPH) were investigated. METHODS: Three-dimensional constructive interference in steady state (3D-CISS) on 3 Tesla MRI was applied to 29 individuals. The morphology and number of VRS in the basal ganglia and white matter were compared between 20 patients with iNPH and nine age-matched controls. The VRS number per hemisphere was classified into three grades: few, moderate, and abundant. RESULTS: Virchow-Robin spaces in the basal ganglia were curved, irregularly sized and shaped, and communicated with the cerebrospinal fluid in the subarachnoid space; they contained perforating arteries. VRS in the white matter were straight, smooth, homogeneously sized and shaped, and did not penetrate the cortex. Arteries were not seen in VRS of the white matter. White matter VRS were sparse in patients with iNPH. In contrast, basal ganglia VRS positively correlated with age. Postoperatively after shunt surgery, VRS in the white matter were mildly decreased in diameter, but not in number. No significant changes were noted in basal ganglia VRS. CONCLUSIONS: The present study revealed different morphological features of VRS in the basal ganglia and white matter. VRS in the basal ganglia were seen as genuine perivascular spaces; while neither communication with subarachnoid spaces nor arteries were seen in white matter VRS, even by 3D-CISS sequences and high-resolution magnetic resonance angiography on 3T-MRI. White matter VRS were sparse in patients with iNPH and they were mildly decreased in diameter, but did not change in number after surgery. At present, it remains unclear whether the white matter VRS are dilated interstitial fluid spaces or cerebral amyloid angiopathy, or both. Further studies are necessary to elucidate the functional role of VRS in normal subjects and patients with iNPH.","Aged;Aged, 80 and over;Basal Ganglia/blood supply/ pathology;Cerebrospinal Fluid;Female;Humans;Hydrocephalus, Normal Pressure/ pathology;Male;Subarachnoid Space;White Matter/blood supply/ pathology","Ishikawa, M.;Yamada, S.;Yamamoto, K.",2015,,10.1186/s12987-015-0010-1,0,3684
3686,Slowly progressive dementia and multiple cerebral cortical infarctions following mitral valve replacement,"We describe the clinicopathological findings of a woman, 83 years of age at the time of death, who demonstrated dementia and numerous cerebral infarctions. She had a history of repeated mitral valve replacements 15 and 13 years prior to death and showed a dull responsive state 1 month after the second operation. Thereafter, dementia manifested and slowly progressed. Brain computed tomography revealed cortical atrophy and ventricular dilatation. Histological examination revealed a large number of minute foci of infarction in the cerebral cortex. Such lesions may have developed in association with the valve replacement and resulted in progressive dementia.",aged;article;brain infarction;case report;clinical feature;computer assisted tomography;dementia;female;histopathology;human;human tissue;image analysis;microscopy;mitral valve replacement;priority journal,"Ishikawa, A.;Kakita, A.;Goto, J.;Tanaka, H.;Takahashi, H.",2001,,,0,
3687,Clinico-pathological evaluation of leukoaraisosis in Alzheimer's disease,"Patients with multi-infarct dementia often have periventricular low density lesions on computed tomography and periventricular hyper-intensity lesions on computed tomography and periventricular hyper-intensity lesions on magnetic resonance imaging. Hachinski called this condition leukoaraiosis and results of previous studies that in multi-infarct dementia leukoaraiosis correlates with cerebral hypoperfusion. Periventricular low-density lesions in the white matter also occur, but their origin and clinical significance insuch patients is unknown. We studied when these lesions develop in patients with Alzheimer's dementia, and whether their presence correlates with clinical findings and cerebral blood flow. The subjects were 37 patients with a probable diagnosis of Alzheimer's dementia, as based on the Neuroepidermilogy Branch of the National Institute of Neurological Disorders and Stroke and the Alzheimer's disease and Related Disorders Association system. Autopsy findings were also available for 2 patients. Patients at higher Functional Assessment Staging of Senile Dementia of Alzheimer Type stages had more extensive periventricular low-density lesions. Patients with the lesions were more likely to have grasp reflex and sucking relex. Blood flow to the frontal and parietal cortices was significantly less in patients with the lesions than in those without the lesions. Neither of the 2 autopsies cases yielded evidence of arteriolosclerosis. Periventricular low-density lesions in Alzheimer's dementia may be closely associated with a degenerative process different from that seen in multi-infarct dementia.",Alzheimer Disease/ pathology/physiopathology;Cerebral Ventricles/ pathology;Cerebrovascular Circulation;Disease Progression;Frontal Lobe/pathology;Humans;Regional Blood Flow;Retrospective Studies,"Ishijima, M.;Imazu, O.;Kitamura, S.;Terashi, A.",1996,Oct,,0,
3688,Prevalence and cognitive performances of vascular cognitive impairment no dementia in Japan: the Osaki-Tajiri Project,"Prevalence, magnetic resonance imaging (MRI) findings, cognitive function and depression are four major aspects of vascular cognitive impairment no dementia (vascular CIND). We performed a community-based study to examine these using 497 community-residents aged 65 years or older. Vascular CIND was defined as a clinical dementia rating (CDR) 0.5 with cerebrovascular disease. Several neuropsychological tests were performed, including MMSE, Geriatric Depression Scale (GDS), and Trail Making Test (TMT). Cerebrovascular disease and white matter lesions were visually assessed using MRI. Prevalence of vascular CIND, localization of cerebrovascular disease, and the relationships amongst MRI findings, white matter lesions, cognitive impairment and depression were analyzed. The prevalence of vascular CIND was 8.5% amongst the total population, corresponding to the rate being 37.2% amongst the CDR 0.5 participants. Compared with the CDR 0, the CDR 0.5 group had more subjects with strategic cerebrovascular disease in the thalamus, etc. No effects of cerebrovascular disease on MMSE and GDS scores were found, but the CDR 0.5/strategic cerebrovascular disease group showed impaired TMT-B scores. In the CDR 0 group, only anterior periventricular hyperintensity was associated with TMT-A score independent of cerebrovascular disease. A vascular CIND population was identified, and executive dysfunction in this population is probably based on an impaired fronto-subcortical circuit.","Aged;Aged, 80 and over;Cognition/ physiology;Cognition Disorders/ epidemiology/ etiology/pathology;Female;Humans;Japan/epidemiology;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests/statistics & numerical data;Risk Factors;Vascular Diseases/ complications/ epidemiology","Ishii, H.;Meguro, K.;Yamaguchi, S.;Ishikawa, H.;Yamadori, A.",2007,Jun,10.1111/j.1468-1331.2007.01781.x,0,
3689,Different MRI findings for normal elderly and very mild Alzheimer's disease in a community: implications for clinical practice the Tajiri Project,"To investigate magnetic resonance imaging (MRI) findings of very mild dementia, 485 participants were randomly selected in a community. Three hundred and forty participants were of Clinical Dementia Rating (CDR) 0 (healthy), 113 were of CDR 0.5 (questionable dementia), and 32 were of CDR 1 and 2 (including 20 Alzheimer's disease, AD). Cortical atrophy, white matter lesion, etc., were visually assessed. We found that each part of the brain showed atrophy in older adults for CDR 0. For CDR 0.5, the relationships between MRI findings and age were weaker, and for AD, there were no such relationship. Atrophy related with dementia severity was found to be limited to the lateral and medial temporal lobes. For CDR 0.5, amygdala atrophy was the only finding indicating CDR effect but no age effect. The amygdala or anterior entorhinal atrophy is important for discriminating very mild dementia from normal elderly.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/epidemiology;Brain/ anatomy & histology;Female;Humans;Japan/epidemiology;Magnetic Resonance Imaging;Male;Prevalence;Retrospective Studies","Ishii, H.;Meguro, K.;Yamaguchi, S.;Hirayama, K.;Tabuchi, M.;Mori, E.;Yamadori, A.",2006,Jan-Feb,10.1016/j.archger.2005.06.002,0,
3690,Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: A case report,"Background: Pure akinesia (PA) is a distinct form of parkinsonism characterized by freezing phenomena. Little is known about brain tumor-associated PA. We highlight the clinicoradiological changes in a patient with PA and central nervous system (CNS) metastases of natural killer/T-cell lymphoma (NKTL).Case presentation: A 68-year-old man with stage IVB extranodal NKTL developed a gait disturbance. Neurological examination of his gait revealed freezing, start hesitation, short step, forward flexion posture, festination and postural instability. Mild facial hypomimia and micrographia were observed. There was no rigidity or tremor in any of the four extremities. Brain magnetic resonance imaging (MRI) displayed T2-hyperintense lesions in the dorsal brainstem, cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) revealed hyperintensity in these regions. Cerebrospinal fluid cytology revealed CD56-positive cells on immunohistochemical staining. The patient's neurological deficits did not respond to L-dopa treatment and intrathecal administration of methotrexate (MTX). Two weeks later, he displayed confusion and generalized convulsions. T2-hyperintense lesions spread to the basal ganglia and the infratentorial regions. Gadolinium enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC revealed diffusion-restricted lesions in the middle cerebellar peduncles, left internal capsules and cerebral white matter. MTX pulse therapy and intrathecal administration of cytosine arabinoside and MTX were performed. Two months later, his ambulatory state was normalized. Brain MRI also revealed marked alleviation of the infratentorial and supratentorial lesions.Conclusions: The clinicoradiological profile of our patient suggested that dorsal ponto-mesencephalic lesions could contribute to the pathogenesis of PA. Physicians should pay more attention to striking CNS seeding of metastatic NKTL. MTX pulse therapy had an excellent effect in improving serious symptoms and brain lesions in our patient. © 2011 Ishihara et al; licensee BioMed Central Ltd.",,"Ishihara, S.;Kano, O.;Ikeda, K.;Shimokawa, R.;Kawabe, K.;Iwasaki, Y.",2011,,,0,
3691,Loss of interhemispheric connectivity in patients with lacunar infarction reflected by diffusion-weighted MR imaging and single-photon emission CT,"BACKGROUND AND PURPOSE: Although decreased neuronal connectivity in white matter has been reported to be a key mechanism of vascular dementia, assessment of white matter changes by diffusion-weighted MR imaging in relation to measures of associative function has not been previously addressed. We evaluated the loss of interhemispheric neuronal connectivity in vascular dementia by measuring diffusional anisotropy of the corpus callosum and determining its relationship to the regional cortical activity as reflected by cortical perfusion. METHODS: Nine patients with multiple lacunar infarction and six healthy volunteers (25-35 years old) were examined. We developed a method to determine the active cortical volume (ACV) by masking iodine-123 iodoamphetamine SPECT scans to eliminate the effect of brain atrophy. The anisotropic rate (AR) was calculated as a ratio of two perpendicular diffusion coefficients in diffusion-weighted MR imaging. RESULTS: Compared with the ACVs of the healthy volunteers, there were significant decreases in the ACVs in the frontal associative areas in the patients, and these were significantly correlated with cognitive scores. The frontal ACVs showed good correlations with the AR of the anterior corpus callosum among all participants; however, only insignificant trends toward correlation were observed between these two parameters within the patient group. CONCLUSION: A possible relationship between diffusional anisotropy of the anterior corpus callosum and frontal associative function was suggested; however, an estimation of the decrease in neuronal connectivity in patients with multiple lacunar infarction in terms of the deterioration in diffusional anisotropy requires further documentation.","Aged;Anisotropy;Brain/pathology/ physiopathology/radionuclide imaging;Cerebral Infarction/ diagnosis/ physiopathology;Diffusion;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neural Pathways/pathology/physiopathology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon","Ishihara, M.;Kumita, S.;Hayashi, H.;Kumazaki, T.",1999,Jun-Jul,,0,
3692,Two cases of a dural arteriovenous fistula mimicking a brain tumor,"SUMMARY: Dural arteriovenous fistula (d-AVF) is relatively rare. Some cases of atypical locations are often difficult to distinguish from other vascular disorders or tumors because those d-AVFs show various onsets, such as subcortical bleeding and venous infarctions. We encountered two cases of d-AVF with severe brain edema that took adequate time to distinguish from brain tumors. A 68-year-old man visited his local physician complaining of dizziness. He was diagnosed with a cerebral infarction due to the presence of an abnormal cerebellar signal on magnetic resonance imaging (MRI) and was treated by drip infusion. However, he did not recover and was admitted to our hospital with suspicion of a brain tumor. A 75-year-old woman with an onset of progressive dementia and gait disturbance showed severe edema of the right-front temporal lobe on MRI. Both these cases were examined by single photon emission computed tomography or positron emission tomography and were scheduled for craniotomy and biopsy based on the diagnosis of brain tumor. We performed preoperative angiography and found d-AVFs. We embolized the d-AVFs with liquid material and both patients recovered well. Brain edema from d-AVF or a tumor can be distinguished by carefully reading the MRI with findings such as the distribution of the edemas, differences on diffusion-weighted images, and contrast-enhanced images. Therefore, it is important to provide initial accurate diagnoses to prevent patient mistrust and irreversible disease conditions.",,"Ishihara, H.;Ishihara, S.;Okawara, M.;Suzuki, M.;Kanazawa, R.;Kohyama, S.;Yamane, F.;Uchino, A.",2009,Mar 31,,0,
3693,Japanese CADASIL case with limited dementia who had the Notch 3 R141C mutation,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia caused by point mutations of the Notch 3 gene. Here, we report a Japanese CADASIL case who displayed limited dementia and had the Notch 3 R141C mutation. The relationship between pathogenesis and the mutation site in Notch 3 is discussed based on the case presented here.",Notch3 receptor;adult;article;CADASIL;case report;dementia;female;gene mutation;genetic disorder;human;Japan;multiinfarct dementia;nuclear magnetic resonance imaging;pathogenesis;point mutation;rare disease;cerebrovascular accident;transient ischemic attack,"Ishibashi, K.;Murata, T.;Miki, Y.;Hara, M.;Mori, H.",2005,,,0,
3694,Asymmetry of post-mortem neuropathology in behavioural-variant frontotemporal dementia,"Antemortem behavioural and anatomic abnormalities have largely been associated with right hemisphere disease in behavioural-variant frontotemporal dementia, but post-mortem neuropathological examination of bilateral hemispheres remains to be defined. Here we measured the severity of post-mortem pathology in both grey and white matter using a validated digital image analysis method in four cortical regions sampled from each hemisphere in 26 patients with behavioural-variant frontotemporal dementia, including those with frontotemporal degeneration (i.e. tau = 9, TDP-43 = 14, or FUS = 1 proteinopathy) or Alzheimer's pathology (n = 2). We calculated an asymmetry index based on the difference in measured pathology from each left-right sample pair. Analysis of the absolute value of the asymmetry index (i.e. degree of asymmetry independent of direction) revealed asymmetric pathology for both grey and white matter in all four regions sampled in frontototemporal degeneration patients with tau or TDP-43 pathology (P </= 0.01). Direct interhemispheric comparisons of regional pathology measurements within-subjects in the combined tauopathy and TDP-43 proteinopathy group found higher pathology in the right orbitofrontal grey matter compared to the left (P < 0.01) and increased pathology in ventrolateral temporal lobe grey matter of the left hemisphere compared to the right (P < 0.02). Preliminary group-wise comparisons between tauopathy and TDP-43 proteinopathy groups found differences in patterns of interhemispheric burden of grey and white matter regional pathology, with greater relative white matter pathology in tauopathies. To test the association of pathology measurement with ante-mortem observations, we performed exploratory analyses in the subset of patients with imaging data (n = 15) and found a direct association for increasing pathologic burden with decreasing cortical thickness in frontotemporal regions on ante-mortem imaging in tauopathy (P = 0.001) and a trend for TDP-43 proteinopathy (P = 0.06). Exploratory clinicopathological correlations demonstrated an association of socially-inappropriate behaviours with asymmetric right orbitofrontal grey matter pathology, and reduced semantically-guided category naming fluency was associated asymmetric white matter pathology in the left ventrolateral temporal region. We conclude that pathologic disease burden is distributed asymmetrically in behavioural-variant frontotemporal dementia, although not universally in the right hemisphere, and this asymmetry contributes to the clinical heterogeneity of the disorder. The basis for this asymmetric profile is enigmatic but may reflect distinct species or strains of tau and TDP-43 pathologies with propensities to spread by distinct cell- and region-specific mechanisms. Patterns of region-specific pathology in the right hemisphere as well as the left hemisphere may play a role in antemortem clinical observations, and these observations may contribute to antemortem identification of molecular pathology in frontotemporal degeneration.",TDP-43 proteinopathy;behavioural variant frontotemporal dementia;digital image analysis histology;frontotemporal degeneration;tauopathy,"Irwin, D. J.;McMillan, C. T.;Xie, S. X.;Rascovsky, K.;Van Deerlin, V. M.;Coslett, H. B.;Hamilton, R.;Aguirre, G. K.;Lee, E. B.;Lee, V. M. Y.;Trojanowski, J. Q.;Grossman, M.",2018,Jan 1,,0,
3695,Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia,"Objective: To determine the prognostic utility of tauopathy-associated single nucleotide polymorphisms (SNPs) in sporadic behavioral-variant frontotemporal dementia (bvFTD). Methods: Eighty-one patients with sporadic bvFTD were genotyped for tauopathy-associated SNPs at rs8070723 (microtubule-associated protein tau [MAPT]) and rs1768208 (myelin-associated oligodendrocyte basic protein [MOBP]). We performed a retrospective case-control study comparing age at onset and disease duration between carriers of ≥1 polymorphism allele and noncarriers for these SNPs. Subanalyses were performed for autopsied subgroups with tauopathy (n = 20) and TDP-43 proteinopathy (n = 12). To identify a potential biological basis for disease duration, neuroimaging measures of white matter integrity were evaluated (n = 37). Results: Carriers of risk allele (T) in rs1768208 (i.e., MOBP RA1) had a shorter median disease duration (TC/TT = 5.5 years, CC = 9.5 years; p = 0.02). This was also found in the subset of cases with autopsy-confirmed tauopathies (p = 0.04) but not with TDP-43 proteinopathies (p > 0.1). By comparison, polymorphisms at rs8070723 (MAPT) had no effect on disease duration (p > 0.1), although carriers of protective allele (G) in rs8070723 had a younger median age at onset (AG/GG = 54.5 years, AA = 58 years; p < 0.01). MOBP RA+ patients had increased radial diffusivity in the superior corona radiata and midbrain, and reduced fractional anisotropy in the superior corona radiata as well as superior and inferior longitudinal fasciculi compared with noncarriers (p < 0.01). Conclusions: The rs1768208 risk polymorphism in MOBP may have prognostic value in bvFTD. MOBP RA+ patients have more severe white matter degeneration in bvFTD that may contribute to shorter disease duration. Future studies are needed to help confirm these findings. © 2014 American Academy of Neurology.",DNA;myelin oligodendrocyte glycoprotein;adult;aged;allele;article;autopsy;case control study;disease duration;female;fractional anisotropy;frontal variant frontotemporal dementia;genotype;human;major clinical study;male;Mini Mental State Examination;nuclear magnetic resonance imaging;onset age;priority journal;retrospective study;single nucleotide polymorphism;tauopathy;TDP 43 proteinopathy;white matter;white matter lesion,"Irwin, D. J.;McMillan, C. T.;Suh, E.;Powers, J.;Rascovsky, K.;Wood, E. M.;Toledo, J. B.;Arnold, S. E.;Lee, V. M. Y.;Van Deerlin, V. M.;Trojanowski, J. Q.;Grossman, M.",2014,,,0,
3696,Deep clinical and neuropathological phenotyping of Pick disease,"OBJECTIVE: To characterize sequential patterns of regional neuropathology and clinical symptoms in a well-characterized cohort of 21 patients with autopsy-confirmed Pick disease. METHODS: Detailed neuropathological examination using 70mum and traditional 6mum sections was performed using thioflavin-S staining and immunohistochemistry for phosphorylated tau, 3R and 4R tau isoforms, ubiquitin, and C-terminally truncated tau. Patterns of regional tau deposition were correlated with clinical data. In a subset of cases (n = 5), converging evidence was obtained using antemortem neuroimaging measures of gray and white matter integrity. RESULTS: Four sequential patterns of pathological tau deposition were identified starting in frontotemporal limbic/paralimbic and neocortical regions (phase I). Sequential involvement was seen in subcortical structures, including basal ganglia, locus coeruleus, and raphe nuclei (phase II), followed by primary motor cortex and precerebellar nuclei (phase III) and finally visual cortex in the most severe (phase IV) cases. Behavioral variant frontotemporal dementia was the predominant clinical phenotype (18 of 21), but all patients eventually developed a social comportment disorder. Pathological tau phases reflected the evolution of clinical symptoms and degeneration on serial antemortem neuroimaging, directly correlated with disease duration and inversely correlated with brain weight at autopsy. The majority of neuronal and glial tau inclusions were 3R tau-positive and 4R tau-negative in sporadic cases. There was a relative abundance of mature tau pathology markers in frontotemporal limbic/paralimbic regions compared to neocortical regions. INTERPRETATION: Pick disease tau neuropathology may originate in limbic/paralimbic cortices. The patterns of tau pathology observed here provide novel insights into the natural history and biology of tau-mediated neurodegeneration.","Aged;Aged, 80 and over;Cerebral Cortex/*pathology;Female;Humans;Immunohistochemistry;Limbic System/*pathology;Magnetic Resonance Imaging;Male;Middle Aged;Phenotype;Pick Disease of the Brain/metabolism/*pathology/physiopathology;Staining and Labeling;Thiazoles;tau Proteins/*metabolism","Irwin, D. J.;Brettschneider, J.;McMillan, C. T.;Cooper, F.;Olm, C.;Arnold, S. E.;Van Deerlin, V. M.;Seeley, W. W.;Miller, B. L.;Lee, E. B.;Lee, V. M.;Grossman, M.;Trojanowski, J. Q.",2016,Feb,10.1002/ana.24559,0,
3697,Grey and white matter correlates of recent and remote autobiographical memory retrieval--insights from the dementias,"The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events.","Aged;Alzheimer Disease/physiopathology;Brain/radiography;Brain Mapping;Case-Control Studies;Dementia/ physiopathology;Female;Frontotemporal Dementia/physiopathology;Gray Matter/ physiopathology/radiography;Humans;Magnetic Resonance Imaging;Male;Memory, Episodic;Memory, Short-Term;Middle Aged;Neuropsychological Tests;White Matter/ physiopathology/radiography","Irish, M.;Hornberger, M.;El Wahsh, S.;Lam, B. Y.;Lah, S.;Miller, L.;Hsieh, S.;Hodges, J. R.;Piguet, O.",2014,,10.1371/journal.pone.0113081,0,
3698,Statistical estimation of physiological brain age as a descriptor of senescence rate during adulthood,"Mapping aging-related brain structure and connectivity changes can be helpful for assessing physiological brain age (PBA), which is distinct from chronological age (CA) because genetic and environmental factors affect individuals differently. This study proposes an approach whereby structural and connectomic information can be combined to estimate PBA as an early biomarker of brain aging. In a cohort of 136 healthy adults, magnetic resonance and diffusion tensor imaging are respectively used to measure cortical thickness over the entire cortical mantle as well as connectivity properties (mean connectivity density and mean fractional anisotropy) for white matter connections. Using multivariate regression, these measurements are then employed to (1) illustrate how CA can be predicated--and thereby also how PBA can be estimated--and to conclude that (2) healthy aging is associated with significant connectome changes during adulthood. Our study illustrates a connectomically-informed statistical approach to PBA estimation, with potential applicability to the clinical identification of patients who exhibit accelerated brain aging, and who are consequently at higher risk for developing mild cognitive impairment or dementia.",,"Irimia, A.;Torgerson, C. M.;Goh, S. Y.;Van Horn, J. D.",2015,Dec,10.1007/s11682-014-9321-0,0,
3699,Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL): a proteiform neurological disease of expanding importance. Reasons for establishing an Italian Registry,,CADASIL/*complications/diagnosis/epidemiology;Humans;Intracranial Arteriosclerosis/*complications/diagnosis;Italy/epidemiology;Magnetic Resonance Imaging;*Registries,"Inzitari, D.;Quattrone, A.;Federico, A.",2006,Nov,10.1007/s10072-006-0700-1,0,
3700,Changes in white matter as determinant of global functional decline in older independent outpatients: Three year follow-up of LADIS (leukoaraiosis and disability) study cohort,"Objective: To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes. Design: Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints. Setting: 11 European centres. Participants: 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy. Main outcome measure: Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke. Results: Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect. Conclusion: The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.",aged;article;brain atrophy;brain infarction;controlled study;daily life activity;dementia;disease severity;female;follow up;functional disease;functional status;gait disorder;atrial fibrillation;human;leukoaraiosis;major clinical study;male;mortality;nuclear magnetic resonance imaging;outpatient;physical disability;priority journal;cerebrovascular accident;white matter,"Inzitari, D.;Pracucci, G.;Poggesi, A.;Carlucci, G.;Barkhof, F.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Ferro, J. M.;Hennerici, M.;Langhorne, P.;O'Brien, J.;Scheltens, P.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Pantoni, L.",2009,,10.1136/bmj.b2477,0,3701
3701,Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort,"OBJECTIVE: To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes. DESIGN: Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints. SETTING: 11 European centres. PARTICIPANTS: 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy. MAIN OUTCOME MEASURE: Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score >/=2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke. RESULTS: Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect. CONCLUSION: The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.",,"Inzitari, D.;Pracucci, G.;Poggesi, A.;Carlucci, G.;Barkhof, F.;Chabriat, H.;Erkinjuntti, T.;Fazekas, F.;Ferro, J. M.;Hennerici, M.;Langhorne, P.;O'Brien, J.;Scheltens, P.;Visser, M. C.;Wahlund, L. O.;Waldemar, G.;Wallin, A.;Pantoni, L.",,2009,,0,
3702,Therapy of vascular dementias,"Vascular dementia (VD) has not to be considered anymore as a univocal nosologic entity. Based on different types of lesions, distinct subtypes of vascular dementia may be identified, each caused by diverse pathophysiological mechanisms. Among these sub-types subcortical vascular dementia (SVD) may represent a well-defined entity in terms of pathophysiology, clinical features and neuroradiological aspects. The picture is characterized by history of arterial hypertension and other vascular risk factors, clinical symptoms and signs including, besides dementia, dysfunctions related to subcortical-frontal circuit damages, and extensive confluent or diffuse abnormalities in the subcortical brain white matter, small deep infarcts as revealed by computed tomographic (CT) or magnetic resonance imaging (MRI) scans. The homogeneity of this clinical-pathological picture is essential for the success of controlled clinical trials in the field of vascular dementia.",,"Inzitari, D.;Lamassa, M.;Pantoni, L.;Basile, A. M.",2004,2004,,0,
3703,The lupus anticoagulant and dementia in non-SLE patients,"The syndrome of circulating anticoagulants in patients without evidence of systemic lupus erythematosus (SLE) has lately become a focus of interest. The clinical features, neuroimaging findings and clinical course of 12 such patients, who presented with neurological symptoms, were analyzed. None of the patients fulfilled the American Rheumatism Association (ARA) criteria of SLE. During a follow-up period of up to 5 years, 9 patients (75%) deteriorated mentally. In 5, cerebrovascular lesions were observed clinically and/or neuroradiologically. Four patients showed slowly progressive mental decline without focal deficits on clinical examination or on CT and MR studies of the brain, except for a small cortical infarct in one case. All patients had radiological evidence of cortical atrophy. Thus, dementia may be a prominent feature among patients with the lupus anticoagulant. Possible underlying mechanisms, such as multi-infarct state, as well as an autoimmune process affecting specifically CNS structures, are discussed.",acetylsalicylic acid;lupus anticoagulant;phospholipid antibody;warfarin;adult;aged;article;autoimmunity;clinical article;controlled study;dementia;drug therapy;female;human;male,"Inzelberg, R.;Bornstein, N. M.;Reider, I.;Korczyn, A. D.",1992,,,0,
3704,A new CSF1R mutation presenting with an extensive white matter lesion mimicking primary progressive multiple sclerosis,"HDLS (Hereditary Diffuse Leukodystrophy with Spheroids) is a hereditary leukodystrophy whose main clinical manifestations include parkinsonism, spasticity, and ataxia. Genetic defects in the colony-stimulating factor 1 receptor (CSF1R) gene have been reported in many HDLS cases. The present report describes a new missense mutation Arg777Gln involving exon 18 of the CSF1R gene in a sporadic patient presenting with tumor-like lesions mimicking primary progressive multiple sclerosis. The patient was initially diagnosed with a progressive variant of multiple sclerosis and received inadequate treatments. Although most HDLS cases have a positive family history, this disease should also be suspected in sporadic patients showing unusual white matter lesions at MRI. © 2013 Elsevier B.V.",colony stimulating factor 1 receptor;colony stimulating factor receptor;cyclophosphamide;methylprednisolone;unclassified drug;adult;amino acid sequence;amino acid substitution;article;assisted ventilation;CADASIL;case report;demyelination;dysphagia;enteric feeding;evoked somatosensory response;exon;hereditary diffuse leukoencephalopathy with spheroids;human;immunotherapy;leukoencephalopathy;lumbar puncture;male;missense mutation;multiple sclerosis;nuclear magnetic resonance imaging;priority journal;speech disorder;tumor spheroid;white matter lesion,"Inui, T.;Kawarai, T.;Fujita, K.;Kawamura, K.;Mitsui, T.;Orlacchio, A.;Kamada, M.;Abe, T.;Izumi, Y.;Kaji, R.",2013,,,0,
3705,Amyloid pathology in the progression to mild cognitive impairment,"The objective of this study was to determine the cognitive and functional decline and development of brain injury in individuals progressing from preclinical (beta-amyloid positive cognitively normal) to prodromal Alzheimer's disease (AD) (beta-amyloid positive mild cognitive impairment [MCI]), and compare this with individuals who progress to MCI in the absence of significant amyloid pathology. Seventy-five cognitively healthy participants who progressed to MCI were followed for 4 years on average and up to 10 years. We tested effects of beta-amyloid (Abeta) on measures of cognition, functional status, depressive symptoms, and brain structure and metabolism. Preclinical AD subjects showed greater cognitive decline in multiple domains and increased cerebrospinal fluid phosphorylated tau levels at baseline while Abeta-negative progressors showed increased rates of white matter hyperintensity accumulation and had a greater frequency of depressive symptoms at baseline. Abeta status did not influence patterns of brain atrophy, but preclinical AD subjects showed greater decline of brain metabolism than Abeta-negative progressors. Several unique features separate the transition from preclinical to prodromal AD from other causes of cognitive decline. These features may facilitate early diagnosis and treatment of AD, especially in clinical trials aimed at halting the progression from preclinical to prodromal AD.",Amyloid;Cognition;Cognitively normal;Mri;Mild cognitive impairment,"Insel, P. S.;Hansson, O.;Mackin, R. S.;Weiner, M.;Mattsson, N.;Alzheimer's Disease Neuroimaging, Initiative",2017,Dec 27,,0,
3706,Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment,"BACKGROUND AND PURPOSE: Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. MATERIALS AND METHODS: We studied 347 patients (217 women, 130 men; mean age, 74 +/- 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. RESULTS: Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). CONCLUSIONS: Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings.",,"Inoue, Y.;Nakajima, M.;Uetani, H.;Hirai, T.;Ueda, M.;Kitajima, M.;Utsunomiya, D.;Watanabe, M.;Hashimoto, M.;Ikeda, M.;Yamashita, Y.;Ando, Y.",2016,Feb,10.3174/ajnr.A4496,0,
3707,A case of adult-onset adrenoleukodystrophy with frontal lobe dysfunction: A novel point mutation in the ABCD1 gene,"We report the case of a 48-year-old man with adult-onset adrenoleukodystrophy (ALD) who developed dementia with subacute onset. He was abulic, indifferent to his surroundings, and without insight with regards to his own disease. An elevated plasma very long chain fatty acid level and a novel point mutation IVS3+2t> g in the ABCD1 gene confirmed the diagnosis of ALD. Diffusion-weighted MRI revealed a high intensity area in the white matter of the frontal lobes. Severe brain hypoperfusion in the frontal lobes was revealed. We believe that this is a rare case of adult-onset adrenoleukodystrophy with predominant frontal lobe dysfunction. © 2012 The Japanese Society of Internal Medicine.",choline;corticotropin;creatinine;cysteine ethyl ester tc 99m;myelin basic protein;n acetylaspartic acid;very long chain fatty acid;ABCD1 gene;adrenoleukodystrophy;adult;article;brain atrophy;brain dysfunction;brain perfusion;case report;cerebrospinal fluid analysis;dementia;frontal lobe;gait disorder;gene;human;male;nuclear magnetic resonance imaging;nuclear magnetic resonance spectroscopy;personality disorder;point mutation;polymerase chain reaction;recall;restriction fragment length polymorphism;sequence analysis;single photon emission computer tomography;speech disorder;tendon reflex;white matter injury,"Inoue, S.;Terada, S.;Matsumoto, T.;Ujike, H.;Uchitomi, Y.",2012,,,0,
3708,A case which seems to be Binswanger syndrome combined with small cerebral infarctions,"The author reports a case of the Binswanger syndrome which was diagnozed by computed tomography of the brain and electroencephalogram. In 1894, Binswanger reported at first eight patients which had slowly progressive dementia with arteriosclerosis in sub-cortex of brain. Pathorogically, this syndrome might be understood as a specific type which appeared the spotty injury in white matter of cerebrum caused by arteriosclerosis of brain. This incidence is very rare. In these cases which had been experienced till now, those diagnosis had been made by means of its dissection. At the time, there was no computed tomography and electroencephalogram, but it is thought possible to make the diagnosis of Binswanger syndrome by ways of computed tomography and elctroencephalogram. This time, computed tomography showed: Small low density image each around Lt. high frontal, Rt. globus pallidus, which indicates small infarctions. Symmetric hypodensity image in both hemispheres of cerebrum and white matter (containing centrum semiovale), which indicates demyelinizations. Ventricular dilatation. Electroencephalogram showed no delta wave but unspecific theta wave 3-5 cycle. These findings were well consistent with Binswanger syndrome which was reported by Binswanger first and reviews of Olszewski. In this case, the patient discharged during the course of this disorder because of almost no healing, and domestic circumstances. Therefore, this patient could not be followed up after discharge. Though it is said that Binswanger syndrome could not be diagnozed only by means of dissection after death, the diagnosis was tried by the approach of computed tomography and electrocephalogram. According to these findings, the author could not help to decide this case which might be a case of Binswanger syndrome. Although an approach to therapy for arteriosclerosis today is tried from various points of views, it is difficult to heal existing arteriosclerotic diseases. In the near future, this syndrome will be a curable disease. Finally, so called convulsive attacks of this type are well controlled by intravenous injection of 20% glucose+diazepam 10 mg (Cercine 10 mg).",,"Inoki, M.",1983,1983,,0,
3709,"Left antero-medical thalamic infarction and symptoms of amnesia, aphasia, and dementia",,amnesia;aphasia;brain infarction;case report;computer analysis;computer assisted tomography;dementia;female;human;male;nuclear magnetic resonance imaging;thalamus,"Ino, T.;Akiguchi, I.;Nabatame, H.;Kameyama, M.",1989,,,0,
3710,Clinical applications of ultra-high field magnetic resonance imaging in multiple sclerosis,"INTRODUCTION: Magnetic resonance imaging (MRI) is of paramount importance for the early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS diagnostic criteria. There is a growing interest in the use of ultra-high-field strength -7 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate of the disease. Areas covered: An overview of 7T MRI applications in MS focusing on increased sensitivity for lesion detection, specificity of the central vein sign and better understanding of MS pathophysiology. Implications for disease diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow higher spatial resolution and better detection of anatomical and pathological features. The high spatial resolution reachable at 7T has been a game changer for neuroimaging applications not only in MS but also in epilepsy, brain tumors, dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has recently been cleared for clinical use by the food and drug administration.",FDA clearance;Multiple sclerosis;central vein sign;gray matter lesions;iron imaging;sodium imaging;ultra-high field MRI;white matter lesions,"Inglese, M.;Fleysher, L.;Oesingmann, N.;Petracca, M.",2018,Jan 30,,0,
3711,Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey,"BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.","Adult;CADASIL/*genetics/*pathology;Exons/genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/*genetics;Receptors, Notch/*genetics;Turkey/epidemiology","Ince, B.;Benbir, G.;Siva, A.;Saip, S.;Utku, U.;Celik, Y.;Necioglu-Orken, D.;Ozturk, S.;Afsar, N.;Aktan, S.;Asil, T.;Bakac, G.;Ekmekci, H.;Gokce, M.;Krespi, Y.;Midi, I.;Varlibas, F.;Citci-Yalcinkaya, B.;Goksan, B.;Uluduz, D.;Uyguner, O.",2014,,10.1159/000360530,0,
3712,Ginat cell arteritis with bilateral obstruction of the internal carotid artery - Report of an autopsy case,"Internal carotid artery involvement and dementia occur infrequently in patients with giant cell (temporal) arteritis. A 75-year-old woman admitted with progressive cognitive decline, drowsiness and headache was diagnosed as having giant cell arteritis bY temporal artery biopsy (TAB). High dose corticosteroid improved inflammatory reaction but did not: improved his cognitive function. Cerebral angiograms showed obstruction of both internal carotid arteries at the siphon. Brain MRI showed only small cerebral infarcts in the basal ganglia and corona radiata bilaterally. However, brain SPECT disclosed reduced cerebral blood flow in the frontal lobe bilaterally. A postmortem examination revealed bilateral parietal infarcts and isolated giant cell arteritis involving the both internal carotid arteries at the Siphon. We speculated that perfusion insufficiency and multiple cerebral infarction due to bilateral internal carotid artery occlusion had caused this neurologic deterioration.",corticosteroid;aged;article;autopsy;basal ganglion;brain angiography;brain blood flow;brain infarction;case report;cognitive defect;dementia;drowsiness;drug megadose;female;frontal lobe;giant cell arteritis;headache;human;internal carotid artery occlusion;nuclear magnetic resonance imaging;single photon emission computer tomography,"Inafuku, T.;Watanabe, M.;Takagi, M.;Hoshino, H.;Morinaga, S.;Koto, A.",1998,,,0,
3713,White matter lesions on brain magnetic resonance imaging scan and 5-year cognitive decline: the Honolulu-Asia aging study,"OBJECTIVES: To study white matter lesions (WMLs) and 5-year cognitive decline in elderly Japanese-American men. DESIGN: Longitudinal cohort study. SETTING: Population-based study in Honolulu, Hawaii. PARTICIPANTS: Japanese-American men aged 74 to 95 from the Honolulu-Asia Aging Study (HAAS) who were free of prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS examination (1994-1996), and returned for cognitive testing 5 years later (N=267). MEASUREMENTS: WMLs were dichotomized as present (grade 3-9, 38.2%) or absent (grade 1-2, 61.8%). Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI), and 5-year cognitive decline was defined as a drop in CASI score of 12 points or more (1 standard deviation). RESULTS: Men with WMLs on MRI at baseline were significantly more likely to experience cognitive decline at 5 years than those without (22.4% vs 34.4%, P=.03). Using multiple logistic regression, adjusting for age, education, apolipoprotein (Apo)E4 allele, large or small infarcts on MRI, baseline CASI score, and hypertension, those with WMLs were significantly more likely to develop 5-year cognitive decline (odds ratio=2.00, 95% confidence interval=1.10-3.65, P=.02). This association was stronger in men who were cognitively intact and free of the ApoE4 genotype and clinical stroke at baseline. CONCLUSION: Presence of WMLs on MRI was significantly associated with higher odds of 5-year cognitive decline in older Japanese-American men. Presence of WMLs may help identify people at risk for developing dementia, who may benefit from early intervention.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ethnology;Asian Americans;Brain/pathology;Cognition Disorders/diagnosis/ ethnology;Cohort Studies;Disability Evaluation;Disease Progression;Hawaii;Health Surveys;Humans;Leukoencephalopathies/ ethnology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Psychometrics;Risk Factors;Tomography, X-Ray Computed","Inaba, M.;White, L.;Bell, C.;Chen, R.;Petrovitch, H.;Launer, L.;Abbott, R. D.;Ross, G. W.;Masaki, K.",2011,Aug,10.1111/j.1532-5415.2011.03490.x,0,
3714,Low intensity areas observed on T2-weighted magnetic resonance imaging of the cerebral cortex in various neurological diseases,"The cerebral cortex of patients with Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS) may show low signal intensity on T2-weighted magnetic resonance images (MRI). Since these low intensity areas (LIA) are also often observed in aged patients with other diseases, we suspected that they might be a non-specific finding. We conducted a retrospective study of LIA in 139 patients with various diseases of the central and peripheral nervous systems, and evaluated their relationship to age and other MRI findings. Brain atrophy, ventricular dilatation, white matter lesions, and LIA were visually evaluated on axial images of the spin echo sequences obtained with a 1.5 tesla (T) system. We found that LIA appeared after age 50 and became more common with advancing age. Their presence correlated with brain atrophy and white matter lesions. They were most frequent in the motor cortex, followed by the occipital and sensory cortices. Their incidence in the motor cortex was significantly higher in patients with central nervous system diseases than in those with peripheral neuropathy. We conclude that LIA are common in old patients with various neurological diseases and suggest that the deposition of iron in the cerebral cortices causes their development.",,"Imon, Y.;Yamaguchi, S.;Yamamura, Y.;Tsuji, S.;Kajima, T.;Ito, K.;Nakamura, S.",1995,Dec,,0,
3715,The effect of age and disease on the MR imaging T2 low signal intensity area in the cerebral cortex,"We retrospectively studied magnetic resonance (MR) images of the brain in 139 patients (16 cases of Alzheimer's disease, 8 cases of Parkinson's disease, 53 cases of multiple cerebral infarct, 33 cases of other central nervous diseases, and 29 cases of peripheral neuropathy) between the age of 6 and 85 years old with a mean age of 60.6 ± 18.5 to examine the appearance of T2 low signal intensity areas (T(2)CLIA) in the cerebral cortex. Motor, occipital, sensory or other cortices were evaluated with long repetition time/echo time (TR/TE) spin-echo sequences and staged into three grades in the moter cortex: none, partial, and whole; and two grades in the others: none or present. In general, T(2)CLIA was not seen in any cortex in patients less than 50 years old, then after 50 years old T(2)CLIA increased with age. Over 70 years of age T(2)CLIA appeared in 50.9% of patients in the whole motor cortex, 88.7% in either whole or partial moter cortex, 47.2% in the occipital cortex, and 20.8% in the sensory cortex. T(2)CLIA was not observed in other cortices. The incidence of T(2)CLIA appearance in the motor cortex was significantly higher in all central nervous diseases than in cases of peripheral neuropathy over 70. T(2)-CLIA showed a correlation with temporal lobe atrophy and white matter lesions in the motor cortex. In the sensory cortex, T(2)CLIA correlated with white matter lesions. These results suggest that T(2)-CLIA may correlate with age or accumulation of nonheme iron in the cortex associated with central nervous diseases.",,"Imon, Y.;Yamaguchi, S.;Katayama, S.;Harada, A.;Yamamura, Y.;Nakamura, S.",1994,1994,,0,
3716,"Gerstmann-Straussler-Scheinker syndrome with a Pro102Leu mutation in the prion protein gene and atypical MRI findings, hyperthermia, tachycardia, and hyperhidrosis","A 64-year-old Japanese woman with Gerstmann-Straussler-Scheinker syndrome (GSS) is reported. She was admitted to our hospital for progressive amnesia, twitching of the right upper limb, and difficulty in speaking and walking for 5 months. Physical examination revealed a fever, tachycardia, and hyperhidrosis without any evidence of inflammation or infection. Neurological examinations demonstrated dementia, frontal lobe signs, and spontaneous myoclonus. She developed akinetic mutism 4 months later. The levels of neuron-specific enolase and 14-3-3 protein were elevated in the cerebrospinal fluid, and serial EEG showed periodic synchronous discharges. DNA analysis of the prion protein gene revealed a Pro102Leu mutation and therefore she was diagnosed as GSS(102). Head MRI showed abnormal high signal intensity by T2 weighted image in bilateral caudate nuclei, putamen, frontal lobes, and white matter around the posterior horn of lateral ventricles at admission, and extension to global cerebral cortex and diffuse deep white matter with marked atrophy of bilateral frontal and cerebellar cortices 4 months later. In (123)I-IMP SPECT study, uptake of RI decreased slightly only in left frontal region at admission, but decreased markedly in bilateral frontal region 4 months later. Analysis of autonomic function (analysis of noradrenarine in plasma and urine, coefficient of variation of R-R intervals before and after giving atenolol, Aschner's eyeball pressure test, intracutaneous atropine and adrenaline injection test) revealed sympathetic hyperactivity but normal parasympathetic activity. This is a very rare case of GSS(102) with atypical MRI findings and clinical features like Creutzfeldt-Jakob disease rather than GSS(102), presenting hyperthermia, tachycardia, and hyperhidrosis caused presumably by sympathetic hyperactivity as well as fatal familial insomnia. Therefore it is suggested that some factors besides the codon mutation in the priori protein gene may influence clinical symptoms in priori disease.",,"Imaiso, Y.;Mitsuo, K.",1998,October/November,,0,
3717,Two cases with acquired immunodeficiency syndrome in our hospital,"We report two cases of AIDS whom we have recently experienced. One patient was a 54-year-old man who admitted our hospital due to third degree burn. In this case, we did not know whether or not he was suffered from AIDS, when he was delivered by the ambulance. In autopsy, pneumocystis carinii pneumonia and renal tuberculosis were found in addition to marked decrease of T cells in lymph nodes. The other patient was a 40-year-old man with remarkable symptoms of central nervous system. Route of infection of HIV is unknown. He had dementia, left hemiplegia, bulbar palsy, progressed to rigid decorticate posture and died of respiratory arrest due to involvement of the brain stem, despite of treatment including use of 3'-azido-2',3'-dideoxythymidine (AZT). Magnetic resonance (MR) images showed progressive cerebral atrophy and a diffuse high signal intensity area of cerebral white matter on T2-weighted",,"Imai, K.;Tanaka, K.;Shibata, K.;Hinoda, Y.;Chiba, S.;Sato, N.;Mori, M.;Kikuchi, K.;Sakano, S.;Imaizumi, H.",1993,Sep,,0,
3718,An 85-year-old right-handed woman with aphasia and left hemiparesis,"We report an 85-year-old woman who developed speech disturbance and left hemiparesis. She had a gradual onset of gait disturbance 3 years prior to the present admission. Five days before admission, she started to pace up and down in her house; she did not want to take food on the following day, and she developed fever of 39°C; it was also noted that she became mute. On the next day, she developed left hemiparesis; she was still mute but was able to communicate by hand writing to some extent. She was admitted to our service on February 24, 1992. On admission, she was alert but mute; her body temperature was 37.1°C, and her BP 110/70 mmHg. The lungs were clear and general physical examination was unremarkable. Neurologic examination revealed that she did not utter even a word. She was unable to understand the examiner's simple questions; communication by hand writing was also difficult, but she could draw her name and a circle; repetition was also impaired. Examination of other higher cerebral functions such as praxis and gnosis was impossible. Her optic fundi were unremarkable; no anisocoria was noted; extraocular muscles appeared intact, and the vestibulo-ocular reflex was normally elicited. The nasolabial fold was shallower on the left; the tongue showed a slight deviation to the left. She had near complete spastic left hemiplegia; deep tendon reflexes were increased bilaterally. A cranial CT scan taken on admission revealed an ill-defined low density area in the right internal capsular region, and diffuse low density change involving the cerebral white matter bilaterally consistent with Binswanger's disease or leukoaraiosis. Her hospital course was complicated by severe pneumonia by MRSA and hemorrhagic tendency. She expired from respiratory failure one month after the admission. The patient was discussed in a neurologic CPC. Evaluation of her speech disturbance was somewhat difficult because of severe mutism on admission and poor information from her family, but it was interesting to note that this apparently right-handed patient developed speech disturbance and left hemiplegia almost simultaneously. The chief discussant arrived at the conclusion that the patient had crossed aphasia of predominantly motor type resulting from a large artery thrombosis involving the right middle cerebral artery; it was also discussed that the lesions responsible for her mutistic speech disturbance might have been caused by combined lesions in the subcallosal fascicle and the middle periventricular white matter in the right hemisphere. Another opinion was that the patient's condition might be a result of loss of attention resulting from a right hemispheric lesion on top of dementia which might well have been present for quite a while judging from her CT scan. Postmortem examination revealed marked atherosclerotic changes in the thoracic as well as abdominal aorta, and severe bronchopneumonia associated with hemorrhagic changes. In the brain, small lacunar infarctions were seen scattered in the putamen and thalamus bilaterally as well as in the cerebral white matter. A discrete relatively fresh infarct was involving the right internal copsule which appeared to have caused left hemiplegia. Myelin pallor in KB staining was prominent in both cerebral white matters. It was somewhat difficult to point out a lesion responsible for her speech disturbance, but it was interesting to note that the white matter ischemic changes were accentuated in the subcallosal area near the anterior horn of the lateral ventricle bilaterally; the latter area was reported to cause severe disturbance of expression of speech when associated with a lesion in the middle one third of the white matter adjacent to the lateral ventricle where fibers innervating the lower motorcranial nerves are passing (Naeser et al. 1988). In our patient, both of those areas appeared to be involved in the right hemisphere; therefore her severe mutism may well have been caused by mirror lesions in the right hemisphere, but definite conclusion was somewhat difficult.",adult;aphasia;brain infarction;case report;computer assisted tomography;controlled study;female;hemiparesis;histopathology;human;human tissue;short survey,"Imai, H.;Matsubayashi, S.;Santo, M. L.;Mori, H.;Suda, K.;Kondo, T.;Mizuno, Y.",1994,,,0,
3719,Sulcal morphology changes and their relationship with cortical thickness and gyral white matter volume in mild cognitive impairment and Alzheimer's disease,"We investigated the changes of sulcal shape (average mean curvature in folded regions and sulcal depth) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) using quantitative surface-based methods in a large sample of magnetic resonance imaging data. Moreover, we observed their relationships with cortical thickness and gyral white matter (WM) volume, while considering age effect. This study involved 85 normal controls (n [men/women]: 36/49, age [mean+/-SD]: 71.1+/-4.9 years), and 100 MCI (44/56, 71.8+/-6.5) and 145 AD subjects (53/92, 72.7+/-7.3). We found significantly lower average mean curvature (greater sulcal widening) and shallower sulcal depth with disease progression from controls to MCI and MCI to AD. The most remarkable change in MCI and AD was sulcal widening observed in the temporal lobe (average mean curvature, control [mean]: 0.564, MCI: 0.534 (5.3% decrease from control), AD: 0.486 (13.8% and 9.0% decrease from control and MCI respectively)). Of the four measurements, the sulcal widening measurement showed the highest sensitivity in revealing group differences between control and MCI, which might be useful for detecting early dementia. Significant reductions in cortical thickness and gyral WM volume also occurred in MCI and AD. Multiple regression analysis demonstrated that a wider and shallower sulcal shape was primarily associated with decreased cortical thickness and gyral WM volume in each group. Age-related trends for the sulcal shape were not strongly found when cortical thickness and gyral WM volume were considered.","Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/complications/ pathology;Cerebral Cortex/ pathology;Cognition Disorders/complications/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Im, K.;Lee, J. M.;Seo, S. W.;Hyung Kim, S.;Kim, S. I.;Na, D. L.",2008,Oct 15,10.1016/j.neuroimage.2008.07.016,0,
3720,Retinal vessel diameters and cerebral small vessel disease: The Rotterdam Scan Study,"The direct visualization of retinal vessels provides a unique opportunity to study cerebral small vessel disease, because these vessels share many features. It was reported that persons with smaller retinal arteriolar-to- venular ratio tended to have more white matter lesions on MRI. It is unclear whether this is due to arteriolar narrowing or venular dilatation. We investigated whether smaller arteriolar or larger venular diameters or both were related to severity and progression of cerebral small vessel disease. We studied 490 persons (60-90 years) without dementia from a population-based cohort study. At baseline ( 1990-1993), retinal arteriolar and venular diameters were measured on digitized images of one eye of each participant. In 1995-1996, participants underwent cerebral MRI scanning. We rated the severity of periventricular white matter lesions on a 9-point scale, approximated a total subcortical white matter lesion volume (range: 0-29.5 ml) and rated the presence of lacunar infarcts. On average 3.3 years later, 279 persons had a second MRI. Changes in periventricular and subcortical white matter lesions were rated with a semi-quantitative scale, and progression was classified as no, minor and marked. An incident infarct was a new infarct on the follow-up MRI. Neither venular nor arteriolar diameters were related to the severity of cerebral small vessel disease. Larger venular diameters were, however, associated with a marked progression of cerebral small vessel disease. Age and gender adjusted odds ratios (ORs) per standard deviation increase were 1.71 [95% confidence interval (CI): 1.11-2.61] for periventricular, 1.72 (95% CI: 1.09-2.71) for subcortical white matter lesion progression and 1.59 (95% CI: 1.06-2.39) for incident lacunar infarcts. These associations were independent of other cardiovascular risk factors. Only the OR for incident lacunar infarcts was attenuated (1.24; 95% CI: 0.72-2.12). No association was observed between arteriolar diameters and progression of cerebral small vessel disease. In conclusion, retinal venular dilatation was related to progression of cerebral small vessel disease. The mechanisms underlying venular dilatation deserve more attention, as they may provide new clues into the pathophysiology of cerebral small vessel disease. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.",,"Ikram, M. K.;De Jong, F. J.;Van Dijk, E. J.;Prins, N. D.;Hofman, A.;Breteler, M. M. B.;De Jong, P. T. V. M.",2006,January,,0,
3721,Brain tissue volumes in the general elderly population. The Rotterdam Scan Study,"We investigated how volumes of cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) varied with age, sex, small vessel disease and cardiovascular risk factors in the Rotterdam Scan Study. Participants (n=490; 60-90 years) were non-demented and 51.0% had hypertension, 4.9% had diabetes mellitus, 17.8% were current smoker and 54.0% were former smoker. We segmented brain MR-images into GM, normal WM, white matter lesion (WML) and CSF. Brain infarcts were rated visually. Volumes were expressed as percentage of intra-cranial volume. With increasing age, volumes of total brain, normal WM and total WM decreased; that of GM remained unchanged; and that of WML increased, in both men and women. Excluding persons with infarcts did not alter these results. Persons with larger load of small vessel disease had smaller brain volume, especially normal WM volume. Diastolic blood pressure, diabetes mellitus and current smoking were also related to smaller brain volume. In the elderly, higher age, small vessel disease and cardiovascular risk factors are associated with smaller brain volume, especially WM volume.","Aged;Aged, 80 and over;Aging/ pathology;Brain/ pathology;Cardiovascular Diseases/ epidemiology/ pathology;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Organ Size;Risk Assessment;Risk Factors","Ikram, M. A.;Vrooman, H. A.;Vernooij, M. W.;van der Lijn, F.;Hofman, A.;van der Lugt, A.;Niessen, W. J.;Breteler, M. M.",2008,Jun,10.1016/j.neurobiolaging.2006.12.012,0,
3722,Brain tissue volumes in relation to cognitive function and risk of dementia,"We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n=490; 60-90 years) were non-demented at baseline (1995-1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus. We performed neuropsychological testing at baseline to assess information processing speed, executive function, memory function and global cognitive function. Participants were followed for incident dementia until January 1, 2005. Larger volumes of CSF and WML were associated with worse performance on all neuropsychological tests, and an increased risk of dementia. Smaller WM volume was related to poorer information processing speed and executive function. In contrast, smaller GM volume was associated with worse memory function and increased risk of dementia. When investigating lobar GM volumes, we found that hippocampal volume and temporal GM volume were most strongly associated with risk of dementia, even in persons without objective and subjective cognitive deficits at baseline, followed by frontal and parietal GM volumes.","Aged;Aged, 80 and over;Brain/*pathology;Cerebrospinal Fluid;Cognition Disorders/*pathology;Cohort Studies;Dementia/*pathology;Female;Follow-Up Studies;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Nerve Fibers, Unmyelinated/pathology;Neuropsychological Tests;Organ Size;Risk Factors","Ikram, M. A.;Vrooman, H. A.;Vernooij, M. W.;den Heijer, T.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Koudstaal, P. J.;Breteler, M. M.",2010,Mar,10.1016/j.neurobiolaging.2008.04.008,1,
3723,Brain tissue volumes and small vessel disease in relation to the risk of mortality,"Brain atrophy and small vessel disease increase the risk of dementia and stroke. In a population-based cohort study (n = 490; 60-90 years) we investigated how volumetric measures of atrophy and small vessel disease were related to mortality and whether this was independent of incident dementia or stroke. Brain volume and hippocampal volume were considered as measures of atrophy, whereas white matter lesions (WML) and lacunar infarcts reflected small vessel disease. We first investigated all-cause mortality in the whole cohort. In subsequent analyses we censored persons at incident dementia or incident stroke. Finally, we separately investigated cardiovascular mortality. The average follow-up was 8.4 years, during which 191 persons died. Brain atrophy and hippocampal atrophy, as well as WML increased the risk of death. The risks associated with hippocampal atrophy attenuated when censoring persons at incident dementia, but not at incident stroke. Censoring at either incident dementia or stroke did not change the risk associated with brain atrophy and WML. Moreover, WML were particularly associated with cardiovascular mortality. © 2007 Elsevier Inc. All rights reserved.",aged;article;brain atrophy;brain damage;brain size;cardiovascular disease;cause of death;controlled study;death;dementia;female;hippocampus;human;incidence;major clinical study;male;microangiopathy;mortality;priority journal;cerebrovascular accident;white matter,"Ikram, M. A.;Vernooij, M. W.;Vrooman, H. A.;Hofman, A.;Breteler, M. M. B.",2009,,,0,
3724,Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease,"BACKGROUND AND PURPOSE: Men, but not women, with unrecognized myocardial infarction (MI) have an increased risk of cardiac events and stroke compared with those without MI or with recognized MI. We investigated whether unrecognized MI is also a risk factor for dementia and cerebral small vessel disease (white matter lesions and brain infarction) in 2 population-based cohort studies. METHODS: In the Rotterdam Study, 6347 participants were classified at baseline (1990 to 1993) into those with recognized MI (subdivided into Q-wave and non-Q-wave MI), with unrecognized MI, and without MI based on electrocardiography and interview and were followed for incident dementia (n=613) until January 1, 2005. In the Rotterdam Scan Study, 436 nondemented persons were similarly classified based on electrocardiography and interview and underwent brain MRI for the assessment of white matter lesions and brain infarction. RESULTS: In men, unrecognized MI was associated with an increased risk of dementia (compared with men without MI hazard ratio, 2.14; 95% CI, 1.37 to 3.35) and with more white matter lesions and more often brain infarction on MRI. In women, no associations were found with unrecognized MI. Recognized MI was not associated with the risk of dementia in either sex. Men, but not women, with recognized MI had more often any brain infarction or asymptomatic brain infarction, especially if they had Q-wave MI. No consistent associations were found between recognized Q-wave or non-Q-wave MI and severity of white matter lesions. Additional adjustment for cardiovascular risk factors did not change the results. CONCLUSIONS: Men with unrecognized MI have an increased risk of dementia and more cerebral small vessel disease.","Aged;Aged, 80 and over;Brain/blood supply/pathology/physiopathology;Brain Ischemia/diagnosis/*epidemiology/physiopathology;Cerebral Arteries/*pathology/physiopathology;Cohort Studies;Comorbidity;Dementia, Vascular/diagnosis/*epidemiology/physiopathology;Electrocardiography;Female;Heart/physiopathology;Humans;Incidence;Male;Microcirculation/*pathology/physiopathology;Middle Aged;Myocardial Infarction/diagnosis/*epidemiology/physiopathology;Nerve Fibers, Myelinated/pathology;Netherlands/epidemiology;Predictive Value of Tests;Prevalence;Prospective Studies;Risk Factors;Sex Distribution;Sex Factors","Ikram, M. A.;van Oijen, M.;de Jong, F. J.;Kors, J. A.;Koudstaal, P. J.;Hofman, A.;Witteman, J. C.;Breteler, M. M.",2008,May,10.1161/strokeaha.107.501106,0,
3725,The Rotterdam Scan Study: design update 2016 and main findings,"Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study.",,"Ikram, M. A.;van der Lugt, A.;Niessen, W. J.;Koudstaal, P. J.;Krestin, G. P.;Hofman, A.;Bos, D.;Vernooij, M. W.",2015,Dec,10.1007/s10654-015-0105-7,0,
3726,A case of polyarteritis nodosa who developed rapidly progressive glomerulonephritis and presented with a tumor-like shadow on head CT in the remission stage,"A 70-year-old woman was admitted to our hospital because of weight loss, fever of unknown origin and rapid deterioration of renal function. Polyarteritis nodosa was diagnosed based on the findings of fever, weight loss, thrombocytosis, arthralgia and crescentic glomerulonephritis with vasculitis in the kidney biopsy specimens. Renal function progressively deteriorated and the patient underwent peritoneal dialysis (PD). Methylprednisolone pulse therapy and subsequent oral prednisolone (PSL) therapy combined with cyclophosphamide (CY) was instituted. Renal function gradually recovered and PD was discontinued 2 weeks later. She was discharged after about 2 months of hospitalization and received a monthly follow-up with daily administration of 10 mg of PSL and 25 mg of CY. Six months after discharge, PN activity was well controlled by PSL and CY, but mental disturbance gradually developed and head CT disclosed a low-density mass shadow that was enhanced with a ring-like appearance by contrast medium similar to a brain tumor. The follow-up CT did not show any enlargement of the mass shadow. One year later, the patient died of uremia and concomitant dementia. Autopsy disclosed cerebral infarct in the relevant site of the mass on CT and the healed stage of angitis in other tissues.",cyclophosphamide;methylprednisolone;prednisolone;aged;article;autopsy;brain infarction;case report;computer assisted tomography;female;glomerulonephritis;human;kidney function;oral drug administration;polyarteritis nodosa,"Ikeda, Y.;Sakemi, T.;Shouno, Y.;Uchida, M.;Nagano, Y.;Kou, T.;Ohtsuka, N.;Baba, N.",1994,,,0,
3727,Encephalopathy due to toluene sniffing. Report of a case with magnetic resonance imaging,"A 27-year-old man with a 10-year history of toluene abuse developed dementia, cerebellar ataxia, dysarthria and pyramidal signs. Magnetic resonance imaging (MRI) revealed atrophy of the cerebrum, corpus callosum, cerebellum and brainstem. The internal capsule showed abnormal intensity. Chronic toluene abuse may affect not only the cerebral and cerebellar cortex of brainstem but also the subcortical cerebral white matter. MRI may be a sensitive tool to use in evaluating the severity and prognosis of the neurological syndrome resulting from toluene abuse.",,"Ikeda, M.;Tsukagoshi, H.",1990,1990,,0,
3728,A case of atypical presenile dementia,"Kosaka (1993) rcvicwcd 16 cases of slowly progressive presenile cortical dementia thought to be a clinicopathological entity with pathological features characterized by circumscribed lobar atrophy, diffuse neurofibrillary tangles, and calcification of the Fahr type, however, the clilical features of this new entity are not known in the description of detail. We report a patient with atypical presenile dementia which appeared to be consistant with that entity, together with the results of a comprehensive neuropsychological and neuroradiological examination. The patient was a 65-year-old right-handed housewife. At about 58 years of age, she started to lose spontaneity and develop a mild memory disturbance. At age 61 she transiently, experienced hallucinations and delusions. During the subsequent 8 years there was a very slight decline in global intellectual efficiency. In addition, she showed slow but definite progression of language disturbances characterized by anemia and loss of ability to grasp the meaning of words, particularly abstract nouns. She performed poorly on tasks with good sensitivity for detecting frontal lobe dysfunction, such as the Wisconsin Card Sorting Test and the hand sequence test. All other cognitive functions appeared to be relatively well preserved, however moderate dyscalculia was present. There was no socially inappropriate or stereotyped behavior, but the patient lost insight into her disease. The patient's activities of daily living on the ward were self-maintained. An EEG was normal. CT and MRI scans showed circumscribed bilateral fronto-temporal atrophy and bilateral mineralization in the basal ganglia and cerebellar white matter. In contrast to the atrophy of typical Pick's disease, the atrophy in our patient was symmetric and dull-edged (not knife-edged) morphologically, and involved the superior temporal gyrus. There was a clear bilateral decrease in rCBF in the temporal and frontal area extending into the parietal region. Thus, the clinical and neuroimaging findings in our patient are unique and differ from the typical features of both Alzheimer's disease and Pick's disease.",aged;Alzheimer disease;article;brain blood flow;case report;female;human;Pick presenile dementia;presenile dementia,"Ikeda, M.;Tanabe, H.;Mori, T.;Komori, K.;Nakagawa, Y.;Tamimukai, S.;Nishimura, T.;Ikeda, K.",1994,,,0,
3729,A case of chorea-acanthocytosis onset with at age 86,"An 86-year-old woman was admitted to our hospital for orobuccolingual dyskinesia. She did not take any medication. Her relatives had no similar symptoms nor consanguineous marriage. Although orobuccolingual dyskinesia was improved by administration of haloperidol for a while, orobuccolingual dyskinesia with biting of tongue and lips, chorea and muscular atrophy in the legs, seizures and dementia appeared half a year after the onset. The decrease of cMAP suggested axonopathy in the extremities by a nerve conduction study. The serum level of CK was normal. The EEG showed generally slow wave activities. A head MRI showed mild atrophy of the bilateral caudate nuclei and frontal lobes with scattered old lacunars in the deep white matter. She was diagnosed as having chorea-acanthocytosis (ChAc) because acanthocytes (10-20%) appeared in the peripheral blood. The normal lipoprotein levels and Kell antigen expression excluded the possibilities of Bassen-Kornzweig syndrome and McLeod syndrome. In all reported cases of ChAc, she was the oldest onset patient. ChAc is warranted in a patient presenting with orobuccolingual dyskinesia with biting, in spite of elderly onset.",haloperidol;lipoprotein;abetalipoproteinemia;acanthocytosis;aged;anamnesis;antigen expression;article;blood group Kell system;brain atrophy;case report;chorea;clinical feature;dyskinesia;female;human;hypertranslucent lung;nerve conduction;neuroimaging;neuropathy;nuclear magnetic resonance imaging;onset age,"Ikawa, M.;Yoneda, M.;Kuriyama, M.",2005,,,0,
3730,Cerebral MR and CT imaging in polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy,Cerebral magnetic resonance (MR) and CT imaging of two patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) showed widespread progressive central and cortical atrophy. Computed tomography revealed calcifications in the area of the caudate nuclei and putamina in both patients. A reduced volume of brain white matter with deep cortical sulci was the most striking MR finding. Rather short relaxation times in periventricular areas adjacent to ventricular bodies were also observed.,,"Iivanainen, M.;Hakola, P.;Erkinjuntti, T.",1984,1984,,0,
3731,A distinct familial presenile dementia with a novel missense mutation in the tau gene,"We report a Japanese family with early onset hereditary frontotemporal dementia and a novel missense mutation (Ser305Asn) in the tau gene. The patients presented with personality changes followed by impaired cognition and memory as well as disorientation, but minimal Parkinsonism. Imaging studies showed fronto-temporal atrophy with ventricular dilatation more on the left, and postmortem examination of the brain revealed numerous neurofibrillary tangles (NFTs) with an unusual morphology and distribution. Silver-stained sections showed ring-shaped NFTs partially surrounding the nucleus that were most prominent in frontal, temporal, insular and postcentral cortices, as well as in dentate gyrus. Cortical NFTs were restricted primarily to layer II, and were composed of straight tubules. Numerous glial cells containing coiled bodies and abundant neuropil threads were detected in cerebral white matter, hippocampus, basal ganglia, diencephalon and brain stem, but no senile plaques or other diagnostic lesions were seen. Both the glial and neuronal tangles were stained by antibodies to phosphorylation-independent and phosphorylation-dependent epitopes in tau. Thus, this novel mutation causes a distinct familial tauopathy.",,"Iijima, M.;Tabira, T.;Poorkaj, P.;Schellenberg, G. D.;Trojanowski, J. Q.;Lee, V. M. Y.;Schmidt, M. L.;Takahashi, K.;Nabika, T.;Matsumoto, T.;Yamashita, Y.;Yoshioka, S.;Ishino, H.",1999,25,,0,
3732,An autopsy case of Binswanger's disease without hypertension and associated with cerebral infarction in the terminal stage,"We report here an autopsy case of Binswanger's disease (BD) without hypertension and associated with cerebral infarction in the terminal stage. The female patient, who was 74 years old at the time of death, had initially demonstrated manic-depressive disorder-like mental disorder, followed by dementia and neurological deficits. A brain CT scan showed white matter low attenuation bilaterally and symmetrically. BD was clinically diagnosed despite the lack of hypertension. In the terminal stage, she suffered an infarction in the left anterior cerebral artery region, and died of pneumonia. Neuropathologically, we found the infarction of the left anterior cerebral artery region, demyelination, fibrillary gliosis, lacunae and arteriosclerosis of the small arteries and arterioles in the white matter.",aged;article;autopsy;Binswanger encephalopathy;brain infarction;case report;dementia;demyelination;female;gliosis;human;human tissue,"Iijima, M.;Ishino, H.;Seno, H.;Inagaki, T.;Haruki, S.",1993,,,0,
3733,An autopsy case of Alzheimer disease with myoclonus and periodic spikes on EEG,"This is a case of Alzheimer disease with myoclonus and periodic spikes on EEG. A 56-year-old man developed progressive dementia and, 3 years later, generalized convulsions. Eight years later, he showed myoclonus and periodic spikes on EEG. Cranial CT showed cortical atrophy and ventricular dilatation. He became apallic and died of pneumonia at the age of 65.9 years after the onset of the disease. The brain weighed 1,050 g. Neuropathologically, diffuse neuronal loss, abundant neurofibrillary tangles and senile plaques, particularly diffuse plaques, were found extensively in the cerebral cortex. The white matter was preserved. In the Ammon's horn, abundant neurofibrillary tangles and senile plaques were observed. Grumose degeneration of the cerebellar dentate nucleus, Kuru plaques or prions were not found. Numerous diffuse plaques of the cerebral cortex have rarely been reported in autopsy cases of Alzheimer disease with myoclonus and periodic spikes on EEG.","Alzheimer Disease/diagnosis/epidemiology/*pathology;Autopsy;Brain/*pathology;Comorbidity;*Electroencephalography;Frontal Lobe/pathology;Hippocampus/pathology;Humans;Male;Middle Aged;Myoclonus/diagnosis/epidemiology/*pathology;Neurofibrillary Tangles/pathology;Tomography, X-Ray Computed","Iijima, M.;Ishino, H.;Seno, H.;Inagaki, T.;Ebara, T.;Yamashita, K.",1994,Sep,,0,
3734,Brain MRI hyperintense lesions and cerebrovascular risk factors in the elderly,"It is known that asymptomatic MRI lesions of the brain are found in elderly subjects, but the significance of the lesions has not been determined. In previous reports, the prevalence of MRI lesions varied from 11% to 59%, but many of the authors indicated a close relationship with cerebrovascular risk factors. We evaluated 76 elderly subjects (over 60 years old, average age +/- SD was 66.7 +/- 4.5) without a history of cerebrovascular disease and dementia, and determined the prevalence of periventricular (PVH), white matter (WMH) and pontine (PH) hyperintensity and risk factors. The severity of MRI lesion was evaluated in T2-weighted images by Fazekas' scoring method of MRI hyperintense lesions. PVH, WMH and PH were graded visually from 0 to 3 by the author and these points are added to the MRI score. In T1-weighted images, we also measured the diameter of the third ventricle, frontal horn and body of the lateral ventricle. Our results were that 62% of subjects had PVH, 64% had WMH and 8% had PH. In regard to risk factors, 38% of subjects had hypertension, 17% had diabetes mellitus, 8% had ischemic heart disease. The PVH (+) group was significantly older (p<0.01) and had larger lateral ventricles (p<0.05) than the PVH (-) group. The WMH (+) group was significantly older (p<0.05) and had higher risk of cerebrovascular disease (p<0.05) than the WMH (-) group. The MRI score was related, but not significantly, to a history of hypertension, diabetes mellitus and ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)",Aged;Aging;Brain/ pathology;Cerebrovascular Disorders/ diagnosis;Female;Humans;Intracranial Arteriosclerosis/diagnosis;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors,"Iidaka, T.",1993,Apr,,0,
3735,Inflammatory cerebral amyloid angiopathy,"Inflammatory cerebral amyloid angiopathy (CAA) typically affects older patients who present with acute or subacute cognitive decline, headache, behavioral change, seizures, and focal neurological deficits. Brain magnetic resonance imaging (MRI) reveals patchy or confluent asymmetric white matter hyperintensities on T2-weighted or fluid-attenuated inversion recovery images, which indicates vasogenic edema, and previous lobar hemorrhages and/or multiple lobar microbleeds on T2<sup>*</sup>-weighted gradient-recalled echo or susceptibility-weighted imaging. Neuropathological findings include frank vasculitis and/or perivascular inflammation with mononuclear or multinucleated giant cells that are associated with amyloid-beta (Abeta)-laden vessels. Importantly, these findings suggest that these patients may respond well to immunosuppressive treatment with high-dose corticosteroids and/or cyclophosphamide. The pathogenesis of this syndrome is still unknown, although anti-Abeta autoantibodies in the cerebrospinal fluid may mediate inflammatory processes against cerebrovascular Abeta. Moreover, MRI findings in patients with inflammatory CAA are very similar to those in patients with Alzheimer's disease who were treated with a monoclonal anti-Abeta antibody, and these findings are called amyloid-related imaging abnormalities (ARIA). Anti-Abeta autoantibodies in the cerebrospinal fluid might be a biomarker of future disease-modifying therapies for patients with Alzheimer's disease and CAA.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/complications;Amyloid beta-Peptides/ metabolism;Cerebral Amyloid Angiopathy/etiology/ metabolism/pathology;Female;Humans;Inflammation/etiology/metabolism/pathology;Male;Middle Aged;Prognosis;Stroke/etiology/metabolism/pathology","Ii, Y.;Tomimoto, H.",2015,Mar,10.11477/mf.1416200132,0,
3736,In vivo detection of cortical microinfarcts on ultrahigh-field MRI,"BACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are detected as small foci restricted to the cerebral cortex in autopsy brains. CMIs are thought to be caused by cerebral amyloid angiopathy (CAA) in the elderly and may be a risk for dementia. We aimed to visualize CMIs, which remain invisible on conventional MRI, using double inversion recovery (DIR) and 3-dimensional fluid attenuated inversion recovery (3D-FLAIR) on 3-Tesla MRI. METHODS: We prospectively performed DIR and 3D-FLAIR images in 70 subjects with Alzheimer disease (AD; n = 47), mild cognitive impairment (n = 14), AD with cerebrovascular disease (CVD; n = 3), vascular dementia (VaD; n = 2), CAA-associated intracerebral hemorrhage (ICH; n = 2) and one each of normal pressure hydrocephalus and dementia with Lewy bodies (DLB). Susceptibility-weighted imaging (SWI) was performed to detect cerebral microbleeds (CMBs). RESULTS: Nine subjects (five of AD and one each of AD with CVD, ICH, VaD, and DLB) had small intracortical high signal lesions on both DIR and 3D-FLAIR images. All the nine subjects accompanied multiple lobar CMBs. These intracortical lesions were located in close proximity to CMBs, and were suggested to be CMIs. CONCLUSIONS: DIR and 3D-FLAIR images may open a way to visualize CMIs.","Adult;Aged;Aged, 80 and over;Algorithms;Cerebral Infarction/ pathology;Female;Humans;Image Enhancement/ methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Reproducibility of Results;Sensitivity and Specificity","Ii, Y.;Maeda, M.;Kida, H.;Matsuo, K.;Shindo, A.;Taniguchi, A.;Tomimoto, H.",2013,Jan,10.1111/j.1552-6569.2012.00722.x,0,
3737,Relation between cerebral white matter damage on CT and MRI and clinical data in DRPLA (pseudo-Huntington form),"We studied the relation between cerebral white matter damage and clinical data in nine patients with dentatorubropallidoluysian atrophy (DRPLA). All patients showed pseudo-Huntington form. The study produced five results. (1) The four of the nine patients showed diffuse hypodensity of the cerebral white matter on CT. We studied one of this four patients by MRI. The hypodensity area on CT showed marked high signal intensity by T2-weighted image on MRI. (2) The onset age was later in the patients with cerebral white matter damage as compared with the patients without this damage. (3) All patients showed subcortical dementia, which was more remarkable in the patient with white matter damage. This suggests the relation between cerebral white matter damage and progression rate of subcortical dementia in DRPLA. (4) Gait disturbance progressed more rapidly in the patients with cerebral white matter damage. (5) The homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) concentration in CSF decreased more remarkably in the patients with white matter damage.","Adult;Atrophy;Brain/ pathology/radiography;Cerebellar Ataxia/pathology;Cerebellar Nuclei/ pathology/radiography;Female;Globus Pallidus/pathology/radiography;Humans;Huntington Disease/ diagnosis/radiography;Lewy Bodies/pathology/radiography;Magnetic Resonance Imaging;Male;Middle Aged;Red Nucleus/pathology/radiography;Tomography, X-Ray Computed","Ihara, Y.;Namba, R.;Nobukuni, K.;Kawai, K.;Kuroda, S.",1991,Aug,,0,
3738,"Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies","The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD. © The Author(s) 2010.",,"Ihara, M.;Polvikoski, T. M.;Hall, R.;Slade, J. Y.;Perry, R. H.;Oakley, A. E.;Englund, E.;O'Brien J, T.;Ince, P. G.;Kalaria, R. N.",2010,May,,0,
3739,Comment: Autosomal dominant small vessel disease due to heterozygous HTRA1 mutations,,serine protease HTRA1;serine proteinase;unclassified drug;alopecia;autosomal dominant disorder;CADASIL;cerebrovascular accident;cerebrovascular disease;dementia;environmental factor;enzyme activity;gene mutation;heterozygosity;human;molecular pathology;neuroimaging;neuropathology;note;nuclear magnetic resonance imaging;priority journal;recessive inheritance;signal transduction;spondylosis,"Ihara, M.",2016,,,0,
3740,[Post Stroke Dementia],"Post-stroke dementia (PSD) is a clinical entity that encompasses all types of dementia following an index stroke. Current evidence suggests that 25-30% of ischemic stroke survivors develop immediate or delayed vascular cognitive impairment or vascular dementia. The type of stroke can be either ischemic, hemorrhagic or hypoperfusive. There are multiple risk factors for PSD including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischemic attack or recurrent stroke and depressive illness. Pre-stroke dementia refers to the occurrence of cognitive impairment before the index stroke, which may be caused by a vascular burden as well as insidious neurodegenerative changes. Neuroimaging determinants of dementia after stroke include silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Published clinical trials have not been promising and there is little information on whether PSD can be prevented using pharmacological agents. Control of vascular disease risk and prevention of recurrent strokes are key to reducing the burden of cognitive decline and post-stroke dementia. Modern imaging and analysis techniques will help to elucidate the mechanism of PSD and establish better treatment.",,"Ihara, M.",2016,Jul,10.11477/mf.1416200506,0,
3741,[The study of neuropsychological alterations following coronary artery bypass operation as predicted by computed tomography scan of the brain],"The objective of this clinical study is to provide information regarding the association between coexistent cerebrovascular disease and neuropsychological abnormalities after coronary artery bypass operations. Computed tomography scan of the brain was performed in 104 patients pre-operatively, and their post-operative neuropsychological functions were evaluated. The patients were categorized as follows according to the CT findings: Seventy-three patients showed normal or slight cerebral cortical atrophy which usually seen in patients over fifty of age (group A). Sixteen showed moderate or severe cortical atrophy (group B). Fifteen patients demonstrated the characteristic findings of Binswanger type; severe white matter hypodensity especially in frontal horns and dilated ventricles (group C). Overt neuropsychological dysfunction was not observed in patient in groups A and B. Six patients in group C showed a combination of dementia, bizarre behavior, disorientation and gait dyspraxia following bypass operations. The pseudobulbar signs were also found in 3 patients. These clinical abnormalities persisted for six days to three weeks, and were most often reversible. Although the underlying mechanism of these deleterious alterations is not elucidated, the ischemic nature of the characteristic white matter lesions was highly suspected. The arteriosclerotic changes of the arteriole of the cerebral cortex and hypoperfusion during cardio-pulmonary bypass were supposed to be responsible. Therefore it was concluded that special attention should be focused on neurological evaluation for bypass surgery in group C patients.","Adult;Aged;Aged, 80 and over;Brain/*radiography;Cerebrovascular Circulation;Cerebrovascular Disorders/physiopathology/*psychology/radiography;*Coronary Artery Bypass;Coronary Disease/surgery;Female;Humans;Male;Middle Aged;Postoperative Period;*Tomography, X-Ray Computed","Iguchi, A.;Sato, K.;Sadahiro, M.;Endo, M.;Yokoyama, H.;Ohmi, M.",1993,Jan,,0,
3742,Anti-aging dock,"Our anti-aging center (AAC) began providing health check-up services to local citizens in western Japan in February 2006, with the mission of promoting 'successful' aging through the employment of anti-aging check-ups, termed 'anti-aging dock' in Japan, using evidence-based 'anti-aging dock' strategies designed to diagnose atherosclerosis based on personal data. Clinical test items routinely received by most patients are as follows: 1) general physical measurement, 2) blood tests and urine analysis, 3) brain MRI/MRA, 4) carotid ultrasound imaging, 5) visceral fat area (VFA) estimation by abdominal CT, 6) brachial ankle pulse wave velocity (baPWV), 7) bone mineral density measurement, 8) stabilometer testing, 9) cognitive function testing, and 10) optional tests, including ambulatory blood pressure monitoring (ABPM). Data from patients providing written informed consent has been used for research. As of December, 2008, the total number of patients has exceeded 1,000. About 50 participants (5%) were found to have cerebral aneurysm, as diagnosed using 3.0 tesla MRI. Of these, 10 patients required surgery, 7 in our hospital and 3 in an affiliated hospital. About 5% of participants were evaluated as probably having dementia; in particular, three patients required treatment for Alzheimer disease. With regard to research, we have focused on the association between cerebral microbleeds and atherosclerotic disease, and the clinical implications of a high ankle-brachial index (ABI).",Aged;Aging;Arteriosclerosis/ diagnosis;Female;Humans;Male;Multiphasic Screening/ methods,"Igase, M.",2009,Jul,,0,
3743,Hypertrophic cardiomyopathy: A rare case of vascular dementia. A case report,"Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infracts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of nonsustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (mutli-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia.",,"Ibtissem, B. H.;Mohamed Néjib, T.;Mohsen, H.",2002,1,,0,
3744,Correlations between clinical findings and magnetization transfer imaging metrics of tissue damage in individuals with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: We obtained magnetization transfer imaging (MTI) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1) to investigate the presence, extent, and nature of pathology in white and gray matter outside proton density (PD)-visible lesions; (2) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans; and (3) to correlate MTI-derived measures of disease burden with age, physical disability, and cognitive performance. METHODS: Dual-echo, T1-weighted, and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects. Magnetization transfer ratio (MTR) values from PD-visible lesions, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM) were measured. Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced. RESULTS: All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects, with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex. The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions. Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects. MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR. Apart from NAGM, average MTR from all other tissues studied significantly decreased with increasing age, physical disability, and cognitive impairment. CONCLUSIONS: PD lesions of individuals with CADASIL have variable degrees of tissue damage. Brain tissue outside PD abnormalities is also damaged. This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL.","Age Factors;Brain [pathology];Cerebral Infarction [diagnosis] [etiology] [pathology];Cognition Disorders [diagnosis] [etiology] [pathology];Dementia, Multi-Infarct [complications] [diagnosis] [genetics] [pathology];Dementia, Vascular [diagnosis] [etiology] [pathology];Genes, Dominant;Magnetic Resonance Imaging;Neuropsychological Tests;Predictive Value of Tests;Proto-Oncogene Proteins [genetics];Receptors, Cell Surface;Severity of Illness Index;Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Iannucci, G.;Dichgans, M.;Rovaris, M.;Brüning, R.;Gasser, T.;Giacomotti, L.;Yousry, T. A.;Filippi, M.",2001,,,0,
3745,The semantic variant of primary progressive aphasia: clinical and neuroimaging evidence in single subjects,"BACKGROUND/AIM: We present a clinical-neuroimaging study in a series of patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA), with the aim to provide clinical-functional correlations of the cognitive and behavioral manifestations at the single-subject level. METHODS: We performed neuropsychological investigations, 18F-FDG-PET single-subject and group analysis, with an optimized SPM voxel-based approach, and correlation analyses. A measurement of white matter integrity by means of diffusion tensor imaging (DTI) was also available for a subgroup of patients. RESULTS: Cognitive assessment confirmed the presence of typical semantic memory deficits in all patients, with a relative sparing of executive, attentional, visuo-constructional, and episodic memory domains. 18F-FDG-PET showed a consistent pattern of cerebral hypometabolism across all patients, which correlated with performance in semantic memory tasks. In addition, a majority of patients also presented with behavioral disturbances associated with metabolic dysfunction in limbic structures. In a subgroup of cases the DTI analysis showed FA abnormalities in the inferior longitudinal and uncinate fasciculi. DISCUSSION: Each svPPA individual had functional derangement involving an extended, connected system within the left temporal lobe, a crucial part of the verbal semantic network, as well as an involvement of limbic structures. The latter was associated with behavioral manifestations and extended beyond the area of atrophy shown by CT scan. CONCLUSION: Single-subject 18F-FDG-PET analysis can account for both cognitive and behavioral alterations in svPPA. This provides useful support to the clinical diagnosis.","Aged;Aged, 80 and over;Aphasia, Primary Progressive/pathology/ radionuclide imaging;Diffusion Tensor Imaging;Female;Fluorodeoxyglucose F18;Humans;Male;Middle Aged;Positron-Emission Tomography;Radiopharmaceuticals;Semantics;Temporal Lobe/pathology/radionuclide imaging","Iaccarino, L.;Crespi, C.;Della Rosa, P. A.;Catricala, E.;Guidi, L.;Marcone, A.;Tagliavini, F.;Magnani, G.;Cappa, S. F.;Perani, D.",2015,,10.1371/journal.pone.0120197,0,
3746,High-b-value diffusion MR imaging and basal nuclei apparent diffusion coefficient measurements in variant and sporadic Creutzfeldt-Jakob disease,"BACKGROUND AND PURPOSE: DWI using a standard b-value of 1000 s/mm(2) has emerged as the most sensitive sequence for the diagnosis of CJD. The purpose of this study was to investigate whether DWI at a high b-value (b = 3000 s/mm(2)) and ADC measurements in the basal nuclei improve the diagnosis of vCJD and sCJD compared with visual assessment of DWI at a standard b-value (b = 1000 s/mm(2)). MATERIALS AND METHODS: Eight patients with vCJD, 9 patients with sCJD, and 5 healthy volunteers underwent DWI at b = 1000 s/mm(2), and 5 vCJD patients, 4 sCJD patients, and 1 growth hormone-related CJD patient underwent DWI at b = 3000 s/mm(2). Two consultant neuroradiologists performed a visual comparison of the b = 1000 and b = 3000 images. Mean MR SI and ADC values were determined for C, P, and DM thalamus ROIs bilaterally at each b-value. SI ratios for each ROI relative to white matter were calculated. RESULTS: In 9 out of 10 patients, the higher b-value images were more sensitive to SI change, particularly in cortex and thalamus, with higher SI ratios at b = 3000 in the DM thalamus. For sCJD at b = 1000, we found significantly lower ADC values in the C and P compared with controls (mean C ADC = 587.3 +/- 84.7 mm(2)/s in sCJD patients versus 722.7 +/- 16.6 mm(2)/s in controls; P = .007), and at b = 3000, the differences were more pronounced. In comparison, in vCJD at b = 1000, ADC values were elevated in the Pu (mean Pu ADC = 837.6 +/- 33.0 mm/s(2) in vCJD patients versus 748.0 +/- 17.3 mm/s(2) in controls; P < .001) but failed to reach significance at b = 3000. CONCLUSIONS: Our results demonstrate that b = 3000 DWI, being more sensitive to slowly diffusing tissue water, is more sensitive to pathology in sCJD than is conventional DWI. High-b-value DWI increases confidence in the radiologic diagnosis of human prion disease.",Adult;Aged;Basal Ganglia/ metabolism/ pathology;Cerebral Cortex/metabolism/pathology;Creutzfeldt-Jakob Syndrome/ metabolism/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Middle Aged;Sensitivity and Specificity;Thalamus/metabolism/pathology;Water/metabolism;Young Adult,"Hyare, H.;Thornton, J.;Stevens, J.;Mead, S.;Rudge, P.;Collinge, J.;Yousry, T. A.;Jager, H. R.",2010,Mar,10.3174/ajnr.A1860,0,
3747,Subacute neurological deterioration with selective axonal injury in patients with acute ischemic stroke following reperfusion of middle cerebral artery occlusion,"To date, the long-term effects of reperfusion on the salvaged brain tissues have not been addressed in the literature. We report 4 cases presenting subacute neurological deteriorations with selective axonal injury following reperfusion therapies for acute ischemic stroke. Our case series based on 4 patients showed common features distinct from those of early reperfusion injury in that (1) the neurological symptoms developed after 1-2 months of reperfusion therapies, (2) these symptoms were accompanied by the subcortical white matter changes on brain MRI, and (3) these findings were mostly reversible with time. This suggests that axons in the reperfused brain may be vulnerable to further neurological injury. © 2011 S. Karger AG, Basel.",alteplase;brain ischemia;aged;arm weakness;article;ataxic aphasia;axonal injury;brain perfusion;case report;cognitive defect;diabetes mellitus;diffusion weighted imaging;female;functional status;atrial fibrillation;hemiparesis;hospitalization;human;hyperlipidemia;hypertension;male;memory disorder;middle cerebral artery occlusion;neurologic disease;neurologic examination;primary progressive aphasia;priority journal;recanalization;reperfusion injury;risk factor;speech disorder;white matter,"Hwang, Y. H.;Kim, Y. W.;Kim, J.;Kim, Y. S.;Park, S. P.;Suh, C. K.",2011,,,0,
3748,25 PRODUCTION OF TRANSGENIC PIGS WITH CreER-MEDIATED ASTROCYTIC-SPECIFIC RECOMBINATION SYSTEM FOR NEUROLOGICAL DISEASE MODELS,"Pigs are one of the most suitable alternative laboratory models than other animals, because they have similar cardiovascular, renal and gastrointestinal organs with those of human. However, in the case of genetically engineered animals, early development of embryos is inhibited by expression of foreign genes, there are many cases of miscarriage or birth early mortality. To overcome these problems, we constructed pig glial fibrillary acidic protein (GFAP) promoter-Cre recombinase fused to a mutated ligand-binding domain of the human oestrogen receptor (CreERT2) and enhanced green fluorescent protein (EGFP)-LoxP transgenes for tamoxifen(TM)-inducible CreERT2-mediated recombination. We then established donor transgenic pig fibroblasts with pGFAP-CreERT2; LCMV-EGFPLoxP transgenes for somatic cell nuclear transfer (SCNT). We produced the SCNT embryos using a Cloud male #5 pGFAP-CreERT2+LCMV-EGFPLoxP donor cell line that was verified in vitro. It was transferred into a surrogate mother and then 5 pGFAP-CreERT2; EGFPLoxP TG piglets were born. By immunofluorescence staining and semi-nested PCR analysis, it was proved that CreER-mediated astrocytic-specific recombination system was operated in some cerebral astrocytic cells after TM-administration to TG pig #4. Additionally, we obtained brain magnetic resonance imaging (MRI) images using 3T-tesla MRI. Brain compartment volume (total brain, grey matter, white matter, cerebellum, brainstem, lateral ventricle, thalamus, midbrain, pons, medulla oblongata, hypophysis) was no significant differences between normal pig and pGFAP-CreERT2; EGFPLoxP transgenic (TG) pig. In summary, we verified the pGFAP promoter-driven CreERT2-LoxP recombination system in TG pig generated by SCNT depending on the TM administration. We suggest that this technology will be a useful tool for studying physiology of astrocytes and generating TG pig model of neurological disease such as Huntington's disease, Alzheimer's disease and brain tumour.",,"Hwang, S. U.;Yoon, J. D.;Eun, K.;Kim, H.;Hyun, S. H.",2016,Jan,,0,
3749,Dural Arteriovenous Fistula Manifested as Rapid Progressive Dementia Successfully Treated by Endovascular Embolization Only,"A 43-year-old male presented with daytime sleepiness at work and indifferent behavior like never before. Two weeks prior to hospital admission, he had episodic memory loss with well preserved remote memory. Brain MRI showed a dural arteriovenous fistula (DAVF) in the right lateral transverse sinus with a bilateral thalamic venous infarction. Cerebral angiography confirmed a right transverse sigmoid dural arteriovenous fistula with a feeding artery of the right occipital artery and left posterior meningeal artery. The DAVF was completely eliminated through multiple endovascular interventions. Recently, endovascular treatment has become one of the main therapeutic options to obliterate a fistulous site, which has led to a rapid diagnostic approach and management of DAVFs with high curative rates. We report a rare case of posterior fossa located at a dural arteriovenous fistula that caused rapid progressive dementia and was successfully eliminated through only endovascular treatment.",Dementia;Dural arteriovenous fistula;Therapeutic embolization,"Hwang, H.;La, Y. K.;Baek, M. S.;Baik, K.;Suh, S. H.;Kim, W. J.",2017,Mar,,0,
3750,Texture analyses of quantitative susceptibility maps to differentiate Alzheimer's disease from cognitive normal and mild cognitive impairment,"PURPOSE: Although a number of studies have focused on finding anatomical regions in which iron concentrations are high, no study has been conducted to examine the overall variations in susceptibility maps of Alzheimer's disease (AD). The objective of this study, therefore, was to differentiate AD from cognitive normal (CN) and mild cognitive impairment (MCI) using a texture analysis of quantitative susceptibility maps (QSMs). METHODS: The study was approved by the local institutional review board, and informed consent was obtained from all subjects. In each participant group-CN, MCI, and AD-18 elderly subjects were enrolled. A fully first-order flow-compensated 3D gradient-echo sequence was run to obtain axial magnitudes and phase images and to produce QSM data. Sagittal structural 3D T1-weighted (3DT1W) images were also obtained with the magnetization-prepared rapid acquisition of gradient-echo sequence to obtain brain tissue images. The first- and second-order texture parameters of the QSMs and 3DT1W images were obtained to evaluate group differences using a one-way analysis of covariance. RESULTS: For the first-order QSM analysis, mean, standard deviation, and covariance of signal intensity separated the subject groups (F = 5.191, p = 0.009). For the second-order analysis, angular second moment, contrast, and correlation separated the subject groups (F = 6.896, p = 0.002). Finally, a receiver operating characteristic curve analysis differentiated MCI from CN in white matter on the QSMs (z = 3.092, p = 0.0020). CONCLUSIONS: This was the first study to evaluate the textures of QSM in AD, which overcame the limitations of voxel-based analyses. The QSM texture analysis successfully distinguished both AD and MCI from CN and outperformed the voxel-based analysis using 3DT1-weighed images in separating MCI from CN. The first-order textures were more efficient in differentiating MCI from CN than did the second-order.",,"Hwang, E. J.;Kim, H. G.;Kim, D.;Rhee, H. Y.;Ryu, C. W.;Liu, T.;Wang, Y.;Jahng, G. H.",2016,Aug,10.1118/1.4958959,0,
3751,Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.",adult;aged;artery disease;article;autosomal dominant disorder;chromosome 19;clinical article;clinical feature;familial disease;female;gene locus;genetic linkage;human;leukoencephalopathy;male;migraine;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident;transient ischemic attack,"Hutchinson, M.;O'Riordan, J.;Javed, M.;Quin, E.;Macerlaine, D.;Willcox, T.;Parfrey, N.;Nagy, T. G.;Tournier-Lasserve, E.",1995,,,0,
3752,Magnetic resonance elastography of frontotemporal dementia,"PURPOSE: To investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease. MATERIALS AND METHODS: We examined five male subjects with bvFTD and nine cognitively normal age-matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre- and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre- and postcentral gyri). RESULTS: Significantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD. CONCLUSION: Future studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474-478.",,"Huston, J., 3rd;Murphy, M. C.;Boeve, B. F.;Fattahi, N.;Arani, A.;Glaser, K. J.;Manduca, A.;Jones, D. T.;Ehman, R. L.",2016,Feb,10.1002/jmri.24977,0,
3753,Brain biopsy-proven intravascular lymphomatosis presenting as rapidly recurrent strokes-two case reports,"Purpose: Intravascular lymphomatosis (IVL) is rare and usually goes undiagnosed until the time of autopsy because of its protean neurological manifestations. Case Report: In this report, we describe two women who developed rapidly recurrent strokes within one to two months. In both cases, brain magnetic resonance imaging showed progression of bilateral cerebral infarcts, and histopathology from brain biopsy confirmed the diagnosis of IVL. The first case did not receive chemotherapy and died of septic shock one month after diagnosis. The second case received whole brain radiotherapy followed by rituximab-containing chemotherapy, and experienced partial improvement of neurological deficits. However, she began to deteriorate in consciousness at 8 months and became stuporous at 10 months after the onset of symptoms. Conclusion: IVL should be considered as a possible etiology if multiple strokes occur in a short period of time.",,"Hung, L. C.;Tsai, J. H.;Wu, C. S.;Dai, Y. C.;Chen, C. C.;Sung, S. F.",2014,March,,0,
3754,Cerebrovascular smooth muscle actin is increased in nondemented subjects with frequent senile plaques at autopsy: Implications for the pathogenesis of Alzheimer disease,"We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: nondemented subjects without significant AD type pathology (""Normal""; n = 20), nondemented subjects with frequent senile plaques at autopsy (""Preclinical AD""; n = 20), and subjects with frontotemporal dementia (""FTD""; n = 10). The groups were matched for sex and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex, and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. Smooth muscle actin expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of nondemented subjects suggest that increased SMA expression might represent a physiological response to neurodegeneration that could prevent or delay overt expression dementia in AD. © 2009 by the American Association of Neuropathologists, Inc.",,"Hulette, C. M.;Ervin, J. F.;Edmonds, Y.;Antoine, S.;Stewart, N.;Szymanski, M. H.;Hayden, K. M.;Pieper, C. F.;Burke, J. R.;Welsh-Bohmer, K. A.",2009,April,,0,
3755,Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease,"BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) is disrupted in small vessel disease patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger disease. METHODS: We selected a subset of 22 Binswanger disease subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice for several years using dynamic contrast-enhanced magnetic resonance imaging. WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were coregistered. WM was divided into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined as 2 mm on each side of the WMH border. WMP was calculated in each of the 3 specific regions. We used paired t test, ANOVA, and Fisher exact test to compare individual changes. RESULTS: WMP was significantly higher in subjects than in controls (P<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52% within the WMH ring (P<0.001; ANOVA). CONCLUSIONS: Increased BBB permeability in normal appearing WM and close to the WMH borders supports a relationship between BBB disruption and the development of WMHs.","Aged;Blood-Brain Barrier/ physiopathology;Cerebral Small Vessel Diseases/pathology/physiopathology;Dementia, Vascular/pathology/physiopathology;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Permeability;White Matter/ pathology","Huisa, B. N.;Caprihan, A.;Thompson, J.;Prestopnik, J.;Qualls, C. R.;Rosenberg, G. A.",2015,Sep,10.1161/strokeaha.115.009589,0,
3756,Markers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease,"Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 +/- 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/metabolism/*pathology;Apolipoprotein E4;Brain/metabolism/*pathology;Cerebrovascular Disorders/*blood/*pathology;Cognition Disorders/etiology/metabolism;Cohort Studies;Female;Humans;Hydroxycholesterols/*blood;Magnetic Resonance Imaging;Male;Retrospective Studies","Hughes, T. M.;Kuller, L. H.;Lopez, O. L.;Becker, J. T.;Evans, R. W.;Sutton-Tyrrell, K.;Rosano, C.",2012,,10.3233/jad-2012-111460,0,
3757,Pulse wave velocity is associated with ?-amyloid deposition in the brains of very elderly adults,"OBJECTIVE: To determine arterial stiffness and ?-amyloid (A?) deposition in the brain of dementia-free older adults. METHODS: We studied a cohort of 91 dementia-free participants aged 83-96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer. RESULTS: A total of 44/91 subjects were A?-positive on PET scan. A? deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being A?-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to A?-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being A?-positive and having high WMH. CONCLUSIONS: Arterial stiffness was associated with A? plaque deposition in the brain, independent of BP and APOE ?4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and A? deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high A? deposition and WMH, which has been suggested to be a ""double hit"" contributing to the development of symptomatic dementia.","Aging [pathology];Amyloid beta-Peptides [metabolism];Blood Pressure [drug effects];Brain [drug effects] [metabolism] [pathology] [radionuclide imaging];Case-Control Studies;Double-Blind Method;Geriatric Assessment;Ginkgo biloba [chemistry];Nerve Fibers, Myelinated [drug effects] [pathology];Neuropsychological Tests;Plant Extracts [pharmacology];Pulse Wave Analysis;Regression Analysis;Retrospective Studies;Vascular Stiffness [drug effects] [physiology];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Hughes, T. M.;Kuller, L. H.;Barinas-Mitchell, E. J.;Mackey, R. H.;McDade, E. M.;Klunk, W. E.;Aizenstein, H. J.;Cohen, A. D.;Snitz, B. E.;Mathis, C. A.;Dekosky, S. T.;Lopez, O. L.",2013,,10.1212/01.wnl.0000435301.64776.37,0,
3758,Pulse wave velocity is associated with beta-amyloid deposition in the brains of very elderly adults,"OBJECTIVE: To determine arterial stiffness and beta-amyloid (Abeta) deposition in the brain of dementia-free older adults. METHODS: We studied a cohort of 91 dementia-free participants aged 83-96 years. In 2009, participants completed brain MRI and PET imaging using Pittsburgh compound B (PiB; a marker of amyloid plaques in human brain). In 2011, we measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed (e.g., brachial ankle PWV [baPWV]) vascular beds, using a noninvasive and automated waveform analyzer. RESULTS: A total of 44/91 subjects were Abeta-positive on PET scan. Abeta deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in baPWV resulted in a 2-fold increase in the odds of being Abeta-positive (p = 0.007). High white matter hyperintensity (WMH) burden was associated with increased central PWV, systolic BP, and MAP. Compared to Abeta-negative individuals with low WMH burden, each SD increase in PWV was associated with a 2-fold to 4-fold increase in the odds of being Abeta-positive and having high WMH. CONCLUSIONS: Arterial stiffness was associated with Abeta plaque deposition in the brain, independent of BP and APOE epsilon4 allele. The associations differed by type of brain abnormality and vascular bed measured (e.g., WMH with central stiffness and Abeta deposition and mixed stiffness). Arterial stiffness was highest in individuals with both high Abeta deposition and WMH, which has been suggested to be a ""double hit"" contributing to the development of symptomatic dementia.","Aged;Aged, 80 and over;Aging/ pathology;Amyloid beta-Peptides/ metabolism;Blood Pressure/drug effects;Brain/drug effects/ metabolism/pathology/radionuclide imaging;Case-Control Studies;Double-Blind Method;Female;Geriatric Assessment;Ginkgo biloba/chemistry;Humans;Male;Nerve Fibers, Myelinated/drug effects/pathology;Neuropsychological Tests;Plant Extracts/pharmacology;Pulse Wave Analysis;Regression Analysis;Retrospective Studies;Vascular Stiffness/drug effects/physiology","Hughes, T. M.;Kuller, L. H.;Barinas-Mitchell, E. J.;Mackey, R. H.;McDade, E. M.;Klunk, W. E.;Aizenstein, H. J.;Cohen, A. D.;Snitz, B. E.;Mathis, C. A.;Dekosky, S. T.;Lopez, O. L.",2013,Nov 5,10.1212/01.wnl.0000435301.64776.37,0,
3759,Interactions of diabetes and postmenopausal hormone therapy on brain volumes: WHIMS,"Background: The Three-City Study observed a significant interaction between circulating levels of estradiol and diabetes on risk for all cause dementia in older women, and the Women's Health Initiative Memory Study (WHIMS) found that diabetes and assignment to hormone therapy (HT) were separately associated with smaller brain volumes and poorer cognition. In addition, randomization to HT vs placebo increased the risk for cognitive impairment in older women. Here, we assessed for an interaction between assignment to HT and diabetes status on brain volumes in the WHIMS cohort. Methods: Brain imaging and cognitive data from 1,402 women from the magnetic resonance imaging sub study of the Women's Health Initiative (WHIMS-MRI) were used. All participants were part of the Women's Health Initiative study, a clinical trial where women were randomized to receive HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo. For this analysis, diabetes status was determined based on self-report of treatment for diabetes or fasting plasma glucose > 126 mg/dL in women where this was measured. Brain volumes were derived from T1-weighted anatomical images. Relationships were assessed using general linear models. Diabetes status, HT assignment, and their interaction were included as fixed effects to assess their relationship with brain volumes and changes in brain volumes. Results: Women with diabetes assigned to HT had a mean [95% confidence interval] decrement of -18.6 [-29.6, -7.6] in total brain volume relative to women with diabetes assigned to placebo. For women without diabetes, this mean decrement was -0.4 [-3.8,3.0].The interaction between diabetes status and HT assignment on brain volume was significant for total brain (p=0.002), grey matter (<0.001), and hippocampal (p=0.006) volumes, but not for white matter (p=0.92) or frontal lobe (p=0.24) volumes. Differences between HT treatment and placebo groups were consistently smaller for women without diabetes. The interaction was not explained by baseline cognitive function or bodymass index. Conclusions: Given that diabetes is known to negatively affect the brain and cognition, these findings support the theory of a healthy cell bias for estrogen action, where estrogen exposure has differential effects depending on the metabolic status of cells.",diabetes mellitus;hormonal therapy;brain size;human;female;cognition;brain;health;risk;nuclear magnetic resonance imaging;white matter;clinical trial;imaging;statistical model;cognitive defect;dementia;confidence interval;gray matter;frontal lobe;estrogen activity;diet restriction;randomization;self report;glucose blood level;memory;exposure;city;placebo;conjugated estrogen;estrogen;estradiol;medroxyprogesterone acetate,"Hugenschmidt, C. E.;Resnick, S. M.;Diaz-Brinton, R.;Manson, J. E.;Yaffe, K.;Vaughan, A. L.;Craft, S.;Edwards, B. J.;Casanova, R.;Masaki, K.;Espeland, M. A.",2015,,,0,
3760,Course and etiology of dysexecutive MCI in a community sample,"Background: Amnestic mild cognitive impairment (aMCI) is associated with an elevated risk of progressing to Alzheimer's disease. Much less is known about the course of dysexecutive mild cognitive impairment (dMCI). The goals of this study were to determine how the profile of cognitive deficits differs over time between patients with dMCI and aMCI, and control subjects; if the type of dementia differs between dMCI and aMCI in patients who progress to dementia; and if dMCI is more associated with stroke and white matter hyperintensity on magnetic resonance imaging (MRI) than aMCI. Methods: The authors undertook a prospective evaluation of an inception cohort of 1167 ethnically diverse elders recruited from an urban community-based sample monitored with clinical and neuropsychological testing for an average of 4.5 years (standard deviation, 0.8 year). A subset of the subjects underwent MRI. We compared four groups of MCI patients: single-domain amnestic and dysexecutive MCI, and multiple-domain MCI with and without executive dysfunction. Results: Compared with aMCI, dMCI was less likely to involve other areas of cognition over time and progress to dementia. None of the 33 single-domain dMCI patients progressed to dementia. The presence of executive dysfunction in multiple-domain MCI did not increase risk of progression to dementia. Patients with multiple-domain MCI with executive dysfunction who progressed to dementia were less likely to have an Alzheimer's-type dementia than MCI patients without executive dysfunction. Patients with dMCI were more likely to experience stroke, but not white matter hyperintensity, detected via MRI than patients with aMCI. Conclusions: dMCI appears to follow a different course, and is less associated with Alzheimer's disease and more associated with stroke than aMCI. © 2013 The Alzheimer's Association. All rights reserved.",,"Huey, E. D.;Manly, J. J.;Tang, M. X.;Schupf, N.;Brickman, A. M.;Manoochehri, M.;Mez, J.;Decarli, C.;Devanand, D. P.;Mayeux, R.",2013,November,,0,
3761,Imaging dementing illnesses,"Dementia is an impairment of mental ability representing a decline from that level previously reached by the individual. It is usually of insidious onset, associated with neurologic changes, and results in the inability to appropriately interact with one's environment. Dementias may be static, progressive, or reversible, and have many etiologies. One percent of the population above age 40 suffers from dementia and this figure rises to 7% above age 80 and 50% above age 90. Forty-five percent of dementias are due to Alzheimer disease (AD) followed closely by vascular dementia. A stage along the way to dementia is mild cognitive impairment (MCI). There are various definitions but the simplest ones refer to a person who has some memory problems but can continue to live independently. A more specific description refers to deficits in two or more areas of cognition >1.5 SD below mean for the individuals age and education. Although previously considered a part of normal aging, a recent study has shown MCI to be a precursor of Alzheimer disease (1). In a cohort of nuns and priests studied annually until they developed MCI or dementia and died. 180 brains in this study have already been autopsied (37 MCI, 60 with no impairment, 53 with dementia). Pathologists measured theamount of AD pathology and cerebral infarcts. Of 37 with MCI, more than half had AD by pathology, 1/3 had infarcts (5 with both) and 14 did not have either pathology. One third of the 180 with average age of 85 had no cognitive decline! Since this study showed MCI patients to have Alzheimer disease pathology in their brains, recognition of MCI clinically is important for institution of therapy, although there has not yet been an effective therapy developed.",,"Huckman, M. S.",2006,Oct 19,,0,
3762,Could changes in arterioles impede the perivascular drainage of interstitial fluid from the cerebral white matter in leukoaraiosis?,"AIMS: Leukoaraiosis (LA) is the increase in fluid in cerebral white matter with hyperintensity on T2-weighted MR imaging that occurs in 25% of individuals over 65 years of age and in Alzheimer's disease. Age, hypertension, diabetes mellitus and cardiac disease are the major risk factors for LA. Ischaemia is considered to be the cause of LA, but the aim of the present study is to assess whether changes in arterioles in LA could impede perivascular lymphatic drainage of interstitial fluid from the cerebral white matter. METHODS: We quantified arteriolosclerosis and immunohistochemical changes in the extracellular matrix in arterioles of cerebral white matter in 20 hypertension autopsy cases with LA and in 10 controls. RESULTS: The ratio of the area immunoreactive for collagen types I, III, V and VI to the cross-sectional area of arterioles was significantly higher in LA patients compared with controls (P < 0.001). Changes were observed in collagen IV and laminin. The walls of white matter arterioles in LA were significantly thicker (P < 0.01), and lumina were significantly smaller (P < 0.01). Arterioles had a significantly higher sclerotic index [1 - (internal/external diameter)] in LA than in adjacent cortex or control white matter (P < 0.01). CONCLUSIONS: Our results show that thickening and sclerosis of the walls of arterioles in cerebral white matter in LA are associated with the accumulation of extracellular matrix components. Although these changes may result in decreased perfusion, they could also impede perivascular lymphatic drainage of interstitial fluid from white matter in LA.","Aged;Arterioles/ pathology/physiopathology;Brain/blood supply/ pathology/physiopathology;Cerebrovascular Disorders/ pathology/physiopathology;Collagen/metabolism;Extracellular Fluid/physiology;Extracellular Matrix/ pathology/physiology;Female;Humans;Hypertension/pathology/physiopathology;Immunohistochemistry;Laminin/metabolism;Leukoaraiosis/ pathology/physiopathology;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Nerve Fibers, Myelinated/pathology/physiology;Sclerosis/pathology/physiopathology","Huang, Y. H.;Zhang, W. W.;Lin, L.;Feng, J.;Zhao, X. X.;Guo, W. H.;Wei, W.",2010,Apr,10.1111/j.1365-2990.2009.01049.x,0,
3763,Hemodynamic factors may play a critical role in neurological deterioration occurring within 72 hrs after lacunar stroke,"Results: Ten out of the 43 patients had END. Patients having END was significantly associated with lower chances of favorable and good outcomes at 3 months (p = 0.01 and p = 0.002, respectively). END was predicted when the non-core hypoperfused area overlapped on the corticospinal tract, which is defined as the expected END profile. Cohen's Kappa coefficient between the 2 image readers to define images of expected END profiles was 0.74. In 15 patients with expected END profile, 9 had END clinically, whereas 28 patients had no expected END profile, and only 1 patient had END (p<0.0001). After adjusting for sex, the expected END profile was still associated with END (odds ratio, 42.2; p = 0.002).Conclusion: Our study demonstrated that the END in acute lacunar stroke is likely related to the transformation of non-core hypoperfused area into infarction in the anatomy of corticospinal tracts.Background: Whether a perfusion defect exists in lacunar infarct and whether it is related to early neurological deterioration (END) is still under debate. The aim of this study was to evaluate whether END in lacunar infarct is related to a perfusion defect using diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and perfusion MR imaging.Methods: One hundred and forty-one consecutive patients had an MRI scan within 30 hours after onset of symptoms and 43 patients with acute lacunar infarct and classic lacunar syndrome were recruited. The MRI sequences included DWI, DTI and cerebral blood flow (CBF) maps to respectively represent the topographic locations of acute infarcts, the corticospinal tract and perfusion defects. The END was defined in reference to the National Institute of Health Stroke Scale (NIHSS) as an increase ≥2 within 72 hours. Cohen's Kappa coefficient was used to examine the reliability between the 2 image readers. A multivariate logistic regression model was constructed adjusting for baseline variables.",,"Huang, Y. C.;Tsai, Y. H.;Lee, J. D.;Weng, H. H.;Lin, L. C.;Lin, Y. H.;Wu, C. Y.;Hsu, H. L.;Lee, M.;Yang, H. T.;Hsu, C. Y.;Pan, Y. T.;Yang, J. T.",2014,,,0,
3764,Vascular cognitive impairment subtypes: A comparative study with cognitive function and MRI,"Objective To explore the discrepancy between vascular cognitive impairment (VCI) subtypes′ patients and cognitive normal (CN) individuals based on cognitive function and brain structural imaging. Methods A case control study was performed. Different VCI subtypes′ patients (n = 62) including 34 VCI no dementia (VCI-ND), 18 vascular dementia (VD) and 10 mixed dementia (MD) were recruited, as well as 50 CN controls in matching with sex, age and education. Evaluated the cognitive function by Mini-Mental State Examination (MMSE), Cognitive Capacity Screening Examination (CCSE) and Combined Mini-Mental-Cognitive Capacity Examinations (CMC), and investigated the brain structural magnetic resonance imaging (MRI) parameters including volumetric changes of focus area, lobar atrophy, white matter leukoaraiosis and lacunar infarction by computer-assisted graphical recognition and processing. Results In comparison with CN controls, the cognitive function assessment of various VCI subtypes′ patients presented progressive decline (P<0.05, for all), but the difference between VD and MD was not significant (P > 0.05). In MRI, the comparison between CN controls and various VCI subtypes′ patients manifested on the following traits: 1) enlargement of bilateral frontal horn volume and third ventricle volume (P< 0.05, for all); 2) an increasing grade of frontal cortical atrophy, temporal cortical atrophy, parietal cortical atrophy and occipital cortical atrophy (P < 0.05, for all); 3) higher grades on white matter leukoaraiosis and lacunar infarction (P<0.05, for all). Moreover, the brain structural imaging variations amplified in advanced cognitive impairment. MD patients, however, without significantly increase in grade of lacunar infarction (P>0.05), were characterized by decline of bilateral hippocampal volume and entorhinal cortical volume, as well as atrophy of temporal lobe (P>0.05, for all). Conclusion The changes of brain MRI can partially reflect the pathological changes of different VCI subtypes′ patients, but are not sensitive to the degree of cognitive impairment. More study should be performed to investigate whether the combination of brain MRI and cognitive function assessment can be clinically used to predict VLI.",,"Huang, L. H.;Huang, L. Q.;Yang, S.;Zhao, Z. X.",2008,December,,0,
3765,A case of hereditary multi-infarct dementia: Mutation in exon 11 of the notch3 gene on chromosome 19,"This study is a report on one 59-year-old male patient with hereditary multi-infarct dementia who came from a family with a positive family history of this disease. The patient primarily presented with dizziness accompanied by vertigo and a positive Romberg's sign. Skull magnetic resonance images showed lacunar infarction in bilateral temporal lobes, bilateral basal ganglias, periventricular white matter and semioval center, and ischemic focus accompanied by white matter degeneration, exhibiting senile morphological brain changes. No abnormalities were observed by skull magnetic resonance angiography. Gene detection further confirmed that there was Arg607Cys heterozygous mutation in exon 11 of the Notch3 gene. No other mutations in exons were detected.",,"Huang, J.;Li, L.;Zhang, B.;Zhang, T.",2011,December,,0,
3766,Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe,"BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). MATERIALS AND METHODS: We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. RESULTS: Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. CONCLUSIONS: We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/psychology;Anisotropy;Axons/ pathology;Cognition Disorders/ pathology/psychology;Diffusion Magnetic Resonance Imaging;Female;Frontal Lobe/pathology;Humans;Male;Middle Aged;Occipital Lobe/pathology;Parietal Lobe;Temporal Lobe/ pathology","Huang, J.;Friedland, R. P.;Auchus, A. P.",2007,Nov-Dec,10.3174/ajnr.A0700,0,
3767,Diffusion tensor imaging of normal appearing white matter and its correlation with cognitive functioning in mild cognitive impairment and Alzheimer's disease,"Diffusion tensor imaging (DTI) was used to examine the microstructural integrity of normal appearing white matter (NAWM) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Significant frontal, temporal, and parietal white matter diffusion tensor changes were demonstrated in MCI and AD compared with normal controls. These changes were correlated with cognitive functioning, and are consistent with a hypothesized loss of axonal processes in affected regions.","Aged;Alzheimer Disease/ pathology/ psychology;Axons/pathology;Brain/pathology;Cognition Disorders/ pathology/ psychology;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Neuropsychological Tests;Psychomotor Performance/physiology","Huang, J.;Auchus, A. P.",2007,Feb,10.1196/annals.1379.021,0,
3768,Distinctive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization,"To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage. © 2012 Elsevier Inc.",,"Huang, H.;Fan, X.;Weiner, M.;Martin-Cook, K.;Xiao, G.;Davis, J.;Devous, M.;Rosenberg, R.;Diaz-Arrastia, R.",2012,September,,0,
3769,Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia,"Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.",,"Huang, C. W.;Tsai, M. H.;Chen, N. C.;Chen, W. H.;Lu, Y. T.;Lui, C. C.;Chang, Y. T.;Chang, W. N.;Chang, A. Y.;Chang, C. C.",2015,Nov 25,10.1160/th14-11-0938,0,
3770,Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease,"BACKGROUND: Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. METHODS: We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. RESULTS: There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. CONCLUSIONS: Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.",Alzheimer's disease;Anatomical structural covariance;Executive control network;Interleukin-1 beta polymorphism;Salience network,"Huang, C. W.;Hsu, S. W.;Tsai, S. J.;Chen, N. C.;Liu, M. E.;Lee, C. C.;Huang, S. H.;Chang, W. N.;Chang, Y. T.;Tsai, W. C.;Chang, C. C.",2017,Jan 18,,0,
3771,Impacts of hyper-homocysteinemia and white matter hyper-intensity in Alzheimer's disease patients with normal creatinine: An MRI-based study with longitudinal follow-up,"Background: White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. Methods: One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. Results: In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. Conclusions: tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows nonsignificant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the twoyear follow-up period. © 2010 Bentham Science Publishers Ltd.",,"Huang, C. W.;Chang, W. N.;Lui, C. C.;Chen, C. F.;Lu, C. H.;Wang, Y. L.;Chen, C.;Juang, Y. Y.;Lin, Y. T.;Tu, M. C.;Chang, C. C.",2010,2010,,0,
3772,Impact of homocysteine on cortical perfusion and cognitive decline in mild Alzheimer's dementia,"BACKGROUND AND PURPOSE: Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation. METHODS: Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow-up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed. RESULTS: In cross-sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (beta = -0.35, P = 0.009). The CASI scores correlated with temporo-parietal PI (Pearson r range 0.3-0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74). CONCLUSIONS: Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.","Aged;Aged, 80 and over;Alzheimer Disease/*blood/complications/*psychology;Brain/radionuclide imaging;Cerebrovascular Circulation/*physiology;Cognition Disorders/*blood/etiology/*psychology;Disease Progression;Female;Homocysteine/*blood;Humans;Male;Middle Aged;Neuropsychological Tests;Perfusion;Risk Factors;Tomography, Emission-Computed, Single-Photon;Alzheimer's disease;cortical perfusion;homocysteine;longitudinal decline;single photon emission computed tomography","Huang, C. W.;Chang, W. N.;Huang, S. H.;Lui, C. C.;Chen, N. C.;Chang, Y. T.;Lee, C. C.;Chang, C. C.;Chang, A. Y.",2013,Aug,10.1111/ene.12159,0,
3773,Effect of BDNF Val66Met polymorphism on regional white matter hyperintensities and cognitive function in elderly males without dementia,"White matter lesions, also termed White Matter Hyperintensities (WMH), on T2-weighted MR images, are common in the elderly population. Of note, their presence is often accompanied with cognitive decline and the risk of dementia. Even though previous brain ischemia and WM lesion studies have been conducted and indicated that brain-derived neurotrophic factor (BDNF) might protect against neuronal cell death, the interaction between regional WMH volume and the BDNF Val66Met polymorphism on the cognitive performance of healthy elderly population remains unclear. To investigate the genetic effect of BDNF on cognitive function and regional WMH in the healthy elderly population, 90 elderly men, without dementia, with a mean age of 80.6 +/- 5.6 y/o were recruited to undergo cognitive tests, structural magnetic resonance imaging (MRI) scans, and genotyping of BDNF alleles. Compared with Met homozygotes, Val homozygotes showed significantly inferior short-term memory (STM) performance (P = .001). A tendency toward dose-dependent effects of the Val allele on WMH volume was found, and Val homozygotes showed larger WMH volume in the temporal (P = .035), the occipital (P = .006), and the global WMH volume (P = .025) than others. Significant interaction effects of BDNF genotypes with temporal WMH volume on STM performance was observed (F1,89 = 4.306, P = .041). Val homozygotes presented steeper negative correlation compared to Met carriers. Mediation analysis also demonstrated that WMH in temporal, limbic, and subcortical regions might mediate the relationship between BDNF's genetic effect and STM performance. Our findings supported the hypothesis that the BDNF Val66Met polymorphism may affect susceptibility to regional WMH volume and such genotype-by-WMH interaction effect is correlated with cognitive decline in non-demented elderly males, in which the Met allele plays a protective role.","Aged;Aged, 80 and over;Aging/ genetics/pathology;Alleles;Brain/ pathology;Brain-Derived Neurotrophic Factor/ genetics;Cognition/ physiology;Genotype;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Polymorphism, Single Nucleotide","Huang, C. C.;Liu, M. E.;Chou, K. H.;Yang, A. C.;Hung, C. C.;Hong, C. J.;Tsai, S. J.;Lin, C. P.",2014,Jan,10.1016/j.psyneuen.2013.09.027,0,
3774,Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment,"Cognitive impairment and brain injury are common in people with HIV/AIDS, even when viral replication is effectively suppressed with combined antiretroviral therapies (cART). Metabolic and structural abnormalities may promote cognitive decline, but we know little about how these measures relate in people on stable cART. Here we used tensor-based morphometry (TBM) to reveal the 3D profile of regional brain volume variations in 210 HIV + patients scanned with whole-brain MRI at 1.5 T (mean age: 48.6 +/- 8.4 years; all receiving cART). We identified brain regions where the degree of atrophy was related to HIV clinical measures and cerebral metabolite levels assessed with magnetic resonance spectroscopy (MRS). Regional brain volume reduction was linked to lower nadir CD4 + count, with a 1-2% white matter volume reduction for each 25-point reduction in nadir CD4 +. Even so, brain volume measured by TBM showed no detectable association with current CD4 + count, AIDS Dementia Complex (ADC) stage, HIV RNA load in plasma or cerebrospinal fluid (CSF), duration of HIV infection, antiretroviral CNS penetration-effectiveness (CPE) scores, or years on cART, after controlling for demographic factors, and for multiple comparisons. Elevated glutamate and glutamine (Glx) and lower N-acetylaspartate (NAA) in the frontal white matter, basal ganglia, and mid frontal cortex - were associated with lower white matter, putamen and thalamus volumes, and ventricular and CSF space expansion. Reductions in brain volumes in the setting of chronic and stable disease are strongly linked to a history of immunosuppression, suggesting that delays in initiating cART may result in imminent and irreversible brain damage.",,"Hua, X.;Boyle, C. P.;Harezlak, J.;Tate, D. F.;Yiannoutsos, C. T.;Cohen, R.;Schifitto, G.;Gongvatana, A.;Zhong, J.;Zhu, T.;Taylor, M. J.;Campbell, T. B.;Daar, E. S.;Alger, J. R.;Singer, E.;Buchthal, S.;Toga, A. W.;Navia, B.;Thompson, P. M.",2013,,10.1016/j.nicl.2013.07.009,0,
3775,Factors related to executive dysfunction after acute infarct,"Results: The average MDRS I/P score of the 177 infarction patients was 24.16±5.21, considerably lower than the average score (32.763.1) of a control group of normal individuals. Patients with infarcts in the corona radiata or basal ganglia had significantly lower MDRS I/P scores that those without infarcts at these locations. The number of infarcts in the basal ganglia was also significantly associated with low MDRS I/P scores. Male gender and low NIHSS score were significantly associated with low MDRS I/P score, and high-density lipoprotein cholesterol was significantly associated with high MDRS I/P score. The number of infarcts in areas other than the basal ganglia as well as corona radiata and the extent of white matter disease had no influence on this score.Conclusions: The number of infarcts in the basal ganglia corona radiata, low NIHSS score, and male gender are significantly and independently related to poor executive function (that is, low MDRS I/P score) after acute infarct. © 2014 Hua et al.Aim: The aim of this study was to investigate the association of infarct location with post-stroke executive dysfunction.Methods: One hundred seventy-seven patients hospitalized with acute infarction were enrolled. General information and NIHSS score at admission were recorded. The infarct site was recorded from magnetic resonance T2-W1 and FLAIR images, and the extent of white matter disease was assessed using the Fazekas score. Seven days after symptoms, executive function was assessed using the validated Chinese version of Mattis Dementia Rating Scale (MDRS) Initiation/Perseveration (I/P) [MDRS I/P].",,"Hua, P.;Pan, X. P.;Hu, R.;Mo, X. E.;Shang, X. Y.;Yang, S. R.",2014,,,0,
3776,MRI volumetric measurement of hippocampal formation based on statistic parametric mapping,"Objective: To study MRI volumetric measurement of hippocampal formation using statistic parametric mapping(SPM) software and to discuss the value of the method applied to Alzheimer's disease (AD). Methods: The SPM software was used to divide the three-dimensional MRI brain image into gray matter, white matter and CSF separately. The bilateral hippocampal formations in both AD group and normal control group were delineated and the volumes were measured. The SPM method was compared with conventional method based on region of interest (ROI), which was the gold standard of volume measurement. The time used in measuring the volume by these two methods were respectively recorded and compared by two independent samples't test. Moreover, 7 physicians measured the left hippocampal formation of one same control with both of the two methods. The frequency distribution and dispersion of data acquired with the two methods were evaluated using standard deviation coefficient. Results: (1) The volume of the bilateral hippocampal formations with SPM method was (1.88±0.07) cm(3) and (1.93±0.08) cm(3) respectively in the AD group, while was (2.99±0.07) cm(3) and (3.02±0.06) cm(3) in the control group. The volume of bilateral hippocampal formations measured by ROI method was (1.87±0.06) cm(3) and (1.91±0.09) cm(3) in the AD group, while was (2.97±0.08)cm(3) and (3.00±0.05) cm(3) in the control group. There was no significant difference between SPM method and conventional ROI method in the AD group and the control group (t = 1.500, 1.617, 1.095, 1.889, P>0.05). However, the time used for delineation and volume measurement was significantly different. The time used in SPM measurement was (38.1±2.0) min, while that in ROI measurement was (55.4±2.4) min (t = - 25.918, P<0.01). (2)The average volumes of the left hippocampal formation with the two methods measured by the 7 physicians were (2.86±0.20) and (2.76±0.52) cm respectively. The frequency distribution of hippocampal formation volume measured by SPM method and ROI method was different. The CV(SPM) was 7% and the CV(R0I) was 19%. Conclusions: The borders of hippocampus formation in brain gray matter could be conveniently delineated by SPM software. The accuracy and repetition of measurement was improved by SPM method. The shorter time used in measurement made it possible for MRI volumetric measurement of hippocampal formation to be applied in assessment of relevant neuropsychiatric diseases. © 2010 by the Chinese Medical Association.",,"Hua, J. M.;Jiang, B.;Zhou, J.;Zhang, W. M.",2010,March,,0,
3777,MRI findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy,"Objective: To investigate the conventional and functional MRI findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Methods: Clinical and MRI data of totally 10 patients with CADASIL were retrospectively analyzed. All of 10 cases underwent conventional MRI plan scan, including 4 of them underwent plan scan and enhanced scan. And there were 8 cases underwent DWI, 4 cases underwent enhanced gradient echo T2 star weighted angiography (ESWAN), 3 cases underwent diffusion kurtosis imaging (DKI), 3 cases underwent arterial spin labeling (ASL) scan and 2 cases underwent MRS. Results: Conventional MRI: CADASIL lesions manifested as symmetric abnormal signals involved bilateral frontal lobe and external capsule in 10 cases, temporal lobe, corona radiate and basal ganglia in 9 cases, temporal pole in 8 cases, occipital lobe and parietal lobe in 8 cases, brain stem in 6 cases and callosum in 4 cases. No enhancement was found in all 4 cases underwent conventional enhanced scan. DWI: Abnormal high signals were found in totally 5 of 8 cases. ESWAN: Multiple plaguliform low signals of right lentiform nucleus, right lobus insularis, left thalamus and subcortex white matter of left temporal lobe were found in 1 of 4 cases. DKI: The mean kurtosis (MK) was increased in white matter of hyperintensities on conventional MRI plan scan. ASL: The cerebral blood flow was decreased in white matter of hyperintensities on conventional MRI plan scan. MRS: The peak of N-acetylaspartate (NAA) in lesion foci was descend. And the lactic acid (Lac) peak was found. Conclusion: MRI findings of CADASIL are characteristic. The lesions mainly involve subcortical structure, temporal pole, external capsule, callosum and brain stem. The functional MRI is helpful for qualitative diagnosis.",angiography;arterial spin labeling;article;basal ganglion;brain blood flow;brain stem;CADASIL;clinical article;clinical feature;corona radiata (brain);corpus callosum;diffusion weighted imaging;functional neuroimaging;human;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;retrospective study;temporal lobe;white matter,"Hu, Y.;Zhang, S.;Yao, Y.;Liu, C.;Li, J.;Zhu, W.",2016,,10.13929/j.1672-8475.2016.10.007,0,
3778,Diffusion kurtosis imaging evaluation of brain white matter microstructure changes in Alzheimer disease,"Objective: To explore the changes of white matter microstructure of Alzheimer disease (AD) with diffusion kurtosis imaging (DKI). Methods: Twenty three cases of AD (AD group) and twenty four cases of volunteers (HC group) underwent conventional MR scan and DKI. Bilateral mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr) and FA values of frontal lobe-white matter (WM), parietal lobe-WM, occipital lobe-WM, temporal lobe-WM, anterior limb of the internal capsule, posterior limb of the internal capsule, external capsule, splenium of the corpus callosum, genu of the corpus callosum, trunk of the corpus callosum were obtained. ROC curve were used to assess the ability of different parameters to diagnosis AD. Results: Compared with HC group, the value of MK, Ka and Kr in AD group significantly decreased in parietal lobe-WM, temporal lobe-WM and external capsule; MK and Kr value also decreased in occipital lobe-WM; MK and Ka value decreased in anterior limb of the internal capsule and genu of the corpus callosum; MK and Kr value decreased in trunk of the corpus callosum; Ka value decreased in splenium of the corpus callosum and posterior limb of the internal capsule (all P<0.05). MD, Da and Dr value increased in frontal lobe-WM, anterior limb of the internal capsule and trunk of the corpus callosum; MD and Dr values increased in parietal lobe-WM, temporal lobe-WM and external capsule; MD and Da value increased in splenium of the corpus callosum; MD value increased in posterior limb of the internal capsule and genu of the corpus callosum; Dr value increased in occipital lobe-WM (all P<0.05). FA value in AD group significantly decreased in frontal lobe-WM, parietal lobe-WM, occipital lobe-WM, temporal lobe-WM, trunk of the corpus callosum, genu of the corpus callosum, anterior limb of the internal capsule and external capsule (all P<0.05). The biggest area under ROC curve which was 0.95 was Dr value in the temporal lobe-WM. The MK, Ka, Kr and FA values showed the positive correlation with MMSE score; the negative correlation was presented between MD, Da, Dr and MMSE score in all regions. Conclusion: DKI parameters may be more accurate in the assessment of microstructure damage in white matter of AD patients. The Dr value in the temporal lobe-WM can be as the best parameter of differentiation AD from controls.",Alzheimer disease;article;capsula interna;clinical article;controlled study;corpus callosum;diffusion kurtosis imaging;external capsule;frontal lobe;human;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;temporal lobe;white matter;white matter microstructure,"Hu, R.;Tan, F.;Chen, X.;Xu, L.;Miao, Y.",2016,,10.13929/j.1003-3289.2016.01.009,0,
3779,Multi-scale features extraction from baseline structure MRI for MCI patient classification and AD early diagnosis,"In this study, we investigate multi-scale features extracted from baseline structural magnetic resonance imaging (MRI) for classifying patients with mild cognitive impairment (MCI), who have either converted or not converted to Alzheimers disease (AD) three years after their baseline visit. Total 549 subjects from the Alzheimers disease Neuroimaging Initiative (ADNI) database are included, and there are 228 Normal controls (NC), 133 MCI patients (71 of them converted to AD within 3 years, referred as MCI converters, or MCIc) and 188 AD patients. The images are preprocessed with the standard voxel-based morphometry method with segmentation of grey matter, white matter and cerebrospinal fluid. Wavelet frame, a multi-scale image representation approach, is applied to extract features of different scales and directions from the processed grey matter image data. The features are extracted for both whole grey matter images and grey matter images of the hippocampus region. The support vector machine is adopted to construct classifiers for MCIc and MCI non-converters (MCInc). The accuracy using a leave-one-out procedure for classification of AD vs. NC and MCIc vs. MCInc is 84.13% and 76.69% respectively, both achieved by local hippocampus data. Our study shows that the proposed multi-scale method is capable of discriminating MCI converters and non-converters, and it can be potentially useful for MCI prognosis in clinical applications.",accuracy;aged;Alzheimer disease;article;brain region;cerebrospinal fluid;controlled study;cortical thickness (brain);diagnostic accuracy;early diagnosis;female;gray matter;hippocampus;human;image analysis;image processing;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;priority journal;prognosis;receiver operating characteristic;sensitivity and specificity;support vector machine;voxel based morphometry;white matter,"Hu, K.;Wang, Y.;Chen, K.;Hou, L.;Zhang, X.",2016,,10.1016/j.neucom.2015.10.043,0,3780
3780,Multi-scale features extraction from baseline structure MRI for MCI patient classification and AD early diagnosis,"In this study, we investigate multi-scale features extracted from baseline structural magnetic resonance imaging (MRI) for classifying patients with mild cognitive impairment (MCI), who have either converted or not converted to Alzheimer's disease (AD) three years after their baseline visit. Total 549 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI) database are included, and there are 228 Normal controls (NC), 133 MCI patients (71 of them converted to AD within 3 years, referred as MCI converters, or MCIc) and 188 AD patients. The images are preprocessed with the standard voxel-based morphometry method with segmentation of grey matter, white matter and cerebrospinal fluid. Wavelet frame, a multi-scale image representation approach, is applied to extract features of different scales and directions from the processed grey matter image data. The features are extracted for both whole grey matter images and grey matter images of the hippocampus region. The support vector machine is adopted to construct classifiers for MCIc and MCI non-converters (MCInc). The accuracy using a leave-one-out procedure for classification of AD vs. NC and MCIc vs. MCInc is 84.13% and 76.69% respectively, both achieved by local hippocampus data. Our study shows that the proposed multi-scale method is capable of discriminating MCI converters and non-converters, and it can be potentially useful for MCI prognosis in clinical applications.",,"Hu, K.;Wang, Y.;Chen, K.;Hou, L.;Zhang, X.",2015,,,0,
3781,Quantitative magnetic resonance imaging differences between Alzheimer disease with and without subcortical lacunes,"Previous reports showed that patients with Alzheimer disease (AD) frequently have coexisting vascular-related pathologies, such as cerebral infarcts and white matter lesions. The aim of this study was to determine the effects of subcortical lacunar infarcts on brain structure in patients with AD. Semi-automated tissue segmentation and volumetry of magnetic resonance imaging data were performed in 38 AD patients without lacunes (AD-L), 24 AD patients with subcortical lacunes (AD+L), and 40 age-matched cognitively healthy subjects without lacunes. The following tissue volumes were quantified, expressed as percentage of total intracranial volume: ventricular cerebrospinal fluid (CSF), sulcal CSF, cortical gray matter (GM), subcortical GM, white matter (WM), white matter signal hyperintensities (WMSH), lacunes, and hippocampus. There was no difference in the Mini-Mental State Examination between the two AD groups. AD+L patients compared with AD-L subjects had significantly greater volumes of WMSH and ventricular CSF spaces (as expected) but smaller sulcal CSF spaces and no significant increase in cortical GM atrophy (both unexpected). In the AD groups, ventricular CSF correlated inversely with cortical GM but not with WM; sulcal CSF correlated inversely with cortical GM and WM. Cognitive impairment was associated with sulcal CSF volume but not with volumes of WMSH or lacunes. In conclusion, the presence of subcortical lacunes in those with AD is associated with more WM lesions and ventriculomegaly but not with cortical atrophy.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology;Atrophy;Brain Infarction/ pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Female;Humans;Male;Mental Status Schedule","Hsu, Y. Y.;Schuff, N.;Amend, D. L.;Du, A. T.;Norman, D.;Chui, H. C.;Jagust, W. J.;Weiner, M. W.",2002,Apr-Jun,,0,
3782,Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease,"BACKGROUND: Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. METHODS: Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. RESULTS: TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. CONCLUSION: The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities.",,"Hsu, Y. H.;Huang, C. F.;Lo, C. P.;Wang, T. L.;Yang, C. C.;Tu, M. C.",2016,,,0,
3783,Posterior Atrophy and Medial Temporal Atrophy Scores Are Associated with Different Symptoms in Patients with Alzheimer's Disease and Mild Cognitive Impairment,"BACKGROUND: Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was correlated with cognitive and non-cognitive symptoms in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients are unclear. METHODS: Patients with probable AD and MCI from a medical center outpatient clinic received attention, memory, language, executive function evaluation and Mini-Mental Status Examination (MMSE). The severity of dementia was rated by the Clinical Dementia Rating (CDR) Sum of Box (CDR-SB). The neuropsychiatric inventory (NPI) subscale of agitation/aggression and mood symptoms was also applied. Magnetic resonance imaging (MRI) was scored visually for the MTA, PA and white matter hyperintensity (WMH) scores. RESULTS: We recruited 129 AD and 31 MCI (mean age 78.8 years, 48% female) patients. MMSE scores, memory, language and executive function were all significantly decreased in individuals with AD than those with MCI (p < 0.01). MTA and PA scores reflected significant atrophy in AD compared to MCI; however, the WMH scores did not differ. The MTA scores were significantly correlated with the frontal, parieto-occipital and global WMH scores (p < 0.01) while the PA scores showed a correlation with the parieto-occipital and temporal WMH scores (p < 0.01). After adjusting for age, education, APOE4 gene and diagnostic group covariates, the MTA scores showed a significant association with MMSE and CDR-SB, while the right side PA scores were significantly associated with NPI-agitation/aggression subscales (p < 0.01). CONCLUSION: Regional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom.",,"Hsu, J. L.;Lee, W. J.;Liao, Y. C.;Lirng, J. F.;Wang, S. J.;Fuh, J. L.",2015,,10.1371/journal.pone.0137121,0,
3784,Microstructural white matter tissue characteristics are modulated by homocysteine: A diffusion tensor imaging study,"Homocysteine level can lead to adverse effects on the brain white matter through endothelial dysfunction, microstructural inflammation, and neurotoxin effects. Despite previously observed associations between elevated homocysteine and macroscopic structural brain changes, it is still unknown whether microstructural associations of homocysteine on brain tissue properties can be observed in healthy subjects with routine MRI. To this end, we investigated potential relationships between homocysteine levels and microstructural measures computed with diffusion tensor imaging (DTI) in a cohort of 338 healthy participants. Significant positive correlations were observed between homocysteine levels and diffusivity measures in the bilateral temporalWM, the brainstem, and the bilateral cerebellar peduncle. This is the first study demonstrating that DTI is sufficiently sensitive to relate microstructural WM properties to homocysteine levels in healthy subjects.",,"Hsu, J. L.;Chen, W. H.;Bai, C. H.;Leu, J. G.;Hsu, C. Y.;Viergever, M. A.;Leemans, A.",2015,,,0,
3785,Aerobic exercise promotes executive functioning and associated functional neuroplasticity,"Background: Vascular cognitive ischaemia (VCI) is a type of cognitive dysfunction, particularly executive functions, secondary to cerebrovascular pathology. Currently, VCI is considered the second most common cause of dementia in later age while many of the risk factors associated could be remedied via physical exercise. Nevertheless, few randomized controlled trials to date have specifically assessed the efficacy of exercise training on cognitive function in this high-risk group. Thus, we conducted a 6-month proof-of-concept randomized controlled trial of thrice-weekly aerobic exercise training (AE) among adults with mild sub-cortical ischemic VCI (SIVCI). This is a secondary analysis of a sub-set of participants who underwent functional MRI. Methods: Seventyone adults (56-96 years) with SIVCI were recruited and randomized (1:1) to one of two experimental groups: 1) 3x/week AE or 2) usual care (UC). The AE classes were 60 minutes in duration and led by certified fitness instructors. Target heart rates were determined by the Karvonen formula. Participants of the UC group received an education seminar on nutrition once per month. SIVCI was confirmed by: 1) evidence of subcortical white matter lesions from neuroimaging; 2) a score of less than 26 on the Montreal Cognitive Assessment (MoCA); and 3) clinical assessment by neurologist. A subset of 21 participants underwent functional MRI using a 3T at baseline and trial completion. During scanning, participants performed the Flanker task (a standardized neuropsychological test for selective attention and response inhibition). Results: After adjusting for age, global cognitive function, visual contrast ability, hip-to-waist ratio and functional comorbidity index, compared with the UC group, the AE group demonstrated significantly reduced reaction time at trial completion during the incongruent conditions with greater accuracy (Table 1; p<0.01). In addition, compared with the UC group, the AE demonstrated lower activation in the supramarginal gyrus and middle temporal gyrus at trial completion (Figure 1). Conclusions: Our results suggest that AE among adults with SIVCI can significantly improve cognitive performance of selective attention and response inhibition (i.e., faster reaction time, increased accuracy) and increase efficiency of brain activations. However, given the small sample size, future studies with larger sample will be required to confirm our findings. (Figure Presented).",manager;human;nerve cell plasticity;aerobic exercise;adult;exercise;reaction time;selective attention;cognition;date (fruit);functional magnetic resonance imaging;dementia;cerebrovascular disease;high risk population;neuropsychological test;randomized controlled trial;executive function;secondary analysis;brain;neurologist;clinical assessment;cognitive defect;randomized controlled trial(topic);white matter lesion;nutrition;neuroimaging;Montreal cognitive assessment;education;heart rate;ischemia;waist hip ratio;comorbidity;fitness;risk factor;nuclear magnetic resonance imaging;supramarginal gyrus;middle temporal gyrus;sample size,"Hsu, C. L.;Wang, S.;Bolandzadeh, N.;Dao, E.;Hsiung, G. Y.;Boyd, L.;Eng, J. J.;Jacova, C.;Liu-Ambrose, T.",2015,,,0,
3786,Detection of early cognitive impairment using AD8 in a young patient with stroke with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome: A case report,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome is a hereditary disease resulting from NOTCH3 gene mutation. The clinical presentations include migraine, recurrent stroke, and cognitive impairment. The severity of cognitive impairment varies in different stages, and early recognition poses a challenge. A 47-year-old lady presented with chronic migraine and sudden onset of hemiparesis. Magnetic resonance imaging revealed compatible findings of CADASIL, which was confirmed by mutation analysis of NOTCH3 gene. Early cognitive impairment was detected by her score of 3 in Ascertain Dementia 8 (AD8) questionnaire and confirmed by detailed neuropsychological assessments. After 21 months of follow-up, deterioration in her cognition and ability to perform instrumental activities of daily living were significant with a follow-up AD8 score of 7. Ascertain Dementia 8 questionnaire is an easy and valid screening tool for early cognitive impairment in patients with CADASIL syndrome. © The Author(s) 2013.",,"Hsieh, I. C.;Kuan, T. S.;Hsieh, P. C.;Chen, S. M.;Yen, W. J.;Chang, W. C.;Lin, I. L.;Lin, Y. C.",2014,March,,0,
3787,Acute simultaneous multiple lacunar infarcts as the initial presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset, dominantly inherited small-vessel disease of the brain caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia, migraine with aura, and mood disturbance. We report a patient with unusual presentation of CADASIL with acute simultaneous multiple subcortical lacunar infarcts as the first manifestation. A 69-year-old man developed confusion, drowsiness, right hemiparesis, and slurred speech following orthopedic surgeries. Brain magnetic resonance imaging revealed diffuse leukoencephalopathy and multiple acute subcortical lacunar infarcts. Brain magnetic resonance angiography, echocardiography and 24-hour electrocardiography were unremarkable. The symptoms improved quickly after treatment with fluid hydration and antiplatelet agent, and his consciousness and mentality totally recovered within 3 days. The NOTCH3 genetic testing showed a heterozygous missense mutation, c.1630C>T (p. Arg544Cys). The experience in this case suggests that brain imaging is important in managing postoperative confusion, and any patient with diffuse leukoencephalopathy of unknown etiology may need to be tested for NOTCH3 mutations. Surgery is an important factor of encephalopathy and acute infarction in individuals with NOTCH3 mutations. Comprehensive presurgical evaluations and proactive perioperative precautions to avoid dehydration and anemia are necessary for patients with CADASIL who are about to receive anesthesia and surgery.",,"Hsiao, C. T.;Chen, Y. C.;Liu, Y. T.;Soong, B. W.;Lee, Y. C.",2015,Jul,10.1016/j.jcma.2015.01.007,0,
3788,Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging,"Brain changes associated with Alzheimer's disease (AD) begin decades before disease diagnosis. While beta-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47-76 years) from the Wisconsin Registry for Alzheimer's Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE epsilon4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI.",,"Hoy, A. R.;Ly, M.;Carlsson, C. M.;Okonkwo, O. C.;Zetterberg, H.;Blennow, K.;Sager, M. A.;Asthana, S.;Johnson, S. C.;Alexander, A. L.;Bendlin, B. B.",2017,,,0,
3789,Race modifies the relationship between cognition and Alzheimer's disease cerebrospinal fluid biomarkers,"BACKGROUND: African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD. METHODS: We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for beta-amyloid (Abeta42, Abeta40), total and phosphorylated tau (t-tau and p-tau181, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), alpha-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume). RESULTS: Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau181 (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p < 0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p = 0.001), and Abeta40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p = 0.013) despite similar levels of Abeta42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/Abeta42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p = 0.001) and p-tau181/Abeta42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p = 0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH. CONCLUSIONS: Despite comparable levels of CSF Abeta42 and Abeta42/Abeta40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.",African American;Amyloid;Dementia;Endothelial dysfunction;Mild cognitive impairment;Tau,"Howell, J. C.;Watts, K. D.;Parker, M. W.;Wu, J.;Kollhoff, A.;Wingo, T. S.;Dorbin, C. D.;Qiu, D.;Hu, W. T.",2017,Nov 2,,0,
3790,"White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly","We determined the prevalence and anatomical location of areas of white matter hyperintensity visualized by magnetic resonance imaging in the brains of 38 late paraphrenic patients with an onset of psychotic illness after the age of 60 and 31 healthy aged community volunteers. All degrees of white matter signal hyperintensity were very common in both groups, and there was no excess of such changes in the brain of patients. Periventricular white matter and subcortical grey matter hyperintensities were significantly associated with both measured diastolic and systolic blood pressure in patients and control subjects. Periventricular and deep white matter, together with subcortical grey matter hyperintensities, were significantly associated with increased age. The excess of such presumed brain-imaging abnormalities previously reported in patients with an onset of psychosis late in life may be a consequence of earlier authors' failure to include examination of appropriate community control populations and to carefully exclude patients with evidence of stroke.","Aged;Aged, 80 and over;Brain/ pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Dementia/ diagnosis/psychology;Depressive Disorder, Major/ diagnosis/psychology;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Neurocognitive Disorders/ diagnosis/psychology;Reference Values","Howard, R.;Cox, T.;Almeida, O.;Mullen, R.;Graves, P.;Reveley, A.;Levy, R.",1995,Jul 15,10.1016/0006-3223(94)00248-2,0,
3791,A method for assessing the significance of abnormalities in HMPO brain SPECT images,"METHODS: A normal atlas for HMPAO rCBF SPECT images was obtained from images of 53 normal controls. Following image registration and normalization, a mean image was extracted, while images representing correlated normal deviants were identified using principal component analysis. These images formed the ""building blocks"" of the atlas. For subsequent images, the atlas was used to create a ""nearest normal equivalent"" image, which was compared to a residual standard deviation image to determine the significance of deviations in the new image. RESULTS: Images from 30 patients (10 with Alzheimer's disease; 12 with single or multiple infarcts; and 8 normals) were analyzed. CONCLUSION: Using an optimal decision level, 10/10 patients with Alzheimer's disease and 11/12 patients with infarcts were correctly identified, with only one false-positive resulting. We utilized a database of images obtained from normal controls to create a normal atlas.","Alzheimer Disease/radionuclide imaging;Brain/physiology/ radionuclide imaging;Cerebral Infarction/radionuclide imaging;Cerebrovascular Disorders/physiopathology/ radionuclide imaging;Humans;Methods;Organotechnetium Compounds;Oximes;Reference Values;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Houston, A. S.;Kemp, P. M.;Macleod, M. A.",1994,Feb,,0,
3792,Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients,"Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated with beta-amyloid pathology. The proton transverse relaxation rate (R(2)) has a strong linear relationship with iron concentrations in healthy brain tissue; however, an independent test of this relationship has not been extended to AD brain tissue. In this study in vitro single spin-echo (SE) measurements were made on tissue samples from four human AD brains using a 4.7T MRI research scanner. R(2) values were calculated for 14 cortical and subcortical gray matter (GM) and white matter (WM) regions. Atomic absorption spectroscopy was used to measure iron concentrations in the corresponding excised brain regions. Significant positive linear correlations were observed between R(2) values and iron concentrations in GM regions assessed across individual tissue samples and data averaged by brain region. With the use of a predictive model for R(2), a threshold iron concentration of 55 microg Fe/g wet tissue was determined above which R(2) appears to be dominated by the affects of iron in AD brain tissue. High-field MRI may therefore be a useful research tool for assessing brain iron changes associated with AD.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Brain/metabolism/*pathology/radiography;*Brain Chemistry;Female;Humans;Iron/*analysis;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Protons","House, M. J.;St Pierre, T. G.;Kowdley, K. V.;Montine, T.;Connor, J.;Beard, J.;Berger, J.;Siddaiah, N.;Shankland, E.;Jin, L. W.",2007,Jan,10.1002/mrm.21118,0,
3793,Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss,"BACKGROUND AND PURPOSE: In Alzheimer disease (AD), elevated brain iron concentrations in gray matter suggest a disruption in iron homeostasis, while demyelination processes in white matter increase the water content. Our aim was to assess whether the transverse proton relaxation rate, or R2, an MR imaging parameter affected by changes in brain iron concentration and water content, was different in elderly participants with mild to severe levels of cognitive impairment compared with healthy controls. METHODS: Twelve elderly participants reporting memory problems and 11 healthy volunteers underwent single-spin-echo MR imaging in a 1.5T scanner, with subsequent neuropsychological testing. R2 data were collected from 14 brain regions in cortical and subcortical gray and white matter. Those with memory complaints were separated into 2 further subgroups: MC1 (no objective cognitive impairment) and MC2 (mild to severe objective cognitive impairment). RESULTS: Mean brain R2 values from the 11 controls correlated strongly (r = 0.94, P < .0001) with reference brain iron concentrations for healthy adults. R2 values in the MC1 and MC2 subgroups were significantly higher in the right temporal cortex and significantly lower in the left internal capsule, compared with healthy controls. R2 values in the MC2 subgroup were significantly lower in the left temporal and frontal white matter, compared with healthy controls. CONCLUSIONS: R2 differences between both subgroups and the healthy controls suggest iron has increased in the temporal cortex, and myelin has been lost from several white matter regions in those with memory complaints, consistent with incipient AD pathogenesis and biochemical data.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/physiopathology;Amnesia/ diagnosis/physiopathology;Brain/pathology;Demyelinating Diseases/ diagnosis;Female;Homeostasis/physiology;Humans;Image Processing, Computer-Assisted/ methods;Iron/ metabolism;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neuropsychology;Reference Values;Statistics as Topic;Water-Electrolyte Balance/ physiology","House, M. J.;St Pierre, T. G.;Foster, J. K.;Martins, R. N.;Clarnette, R.",2006,Feb,,0,
3794,The relationship between intellectual impairment and mood disorder in the first year after stroke,"In a community-based study of patients with a first-ever stroke, intellectual impairment (as defined by scores on a common screening test for dementia, the Mini-Mental State Examination) was found in 26% at 1 month post-stroke, and in 21% at 6 and 12 month follow-up. Low scores on the screening test were associated with greater age, physical disability before the stroke, larger stroke lesion volumes as measured on CT scan, and non-stroke changes such as atrophy and white matter low attenuation on the CT scan. There was a negative correlation between scores on the Mini-Mental State Examination and symptom levels on two measures of mood disorder. However, there was no evidence of a specific relationship between major depression and low scores on the Mini-Mental State. We examined various aspects of the relationship between mood symptoms and low scores on the Mini-Mental State, but found no evidence to support the suggestion that this relationship represented an example of depressive pseudodementia. We discuss the significance of our findings for clinical psychiatry and neuropsychology.","Adolescent;Adult;Aged;Aged, 80 and over;Brain Damage, Chronic/diagnosis/*psychology;Cerebrovascular Disorders/diagnosis/*psychology;Dementia/diagnosis/psychology;Depressive Disorder/diagnosis/psychology;Female;Follow-Up Studies;Humans;*Intelligence;Male;Middle Aged;Mood Disorders/diagnosis/*psychology;Neurocognitive Disorders/diagnosis/*psychology;Neurologic Examination;*Neuropsychological Tests;Psychometrics;Tomography, X-Ray Computed","House, A.;Dennis, M.;Warlow, C.;Hawton, K.;Molyneux, A.",1990,Nov,,0,
3795,Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial,"BACKGROUND AND PURPOSE: Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. METHODS: Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion-diffusion mismatch not progressing to infarction after 1 month. RESULTS: Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (P=0.006), and National Institutes of Health Stroke Scale score on admission was lower (P=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (P=0.0003). CONCLUSIONS: Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00975962.","Allied Health Personnel;Brain Ischemia [drug therapy] [therapy];Cerebral Infarction [epidemiology] [pathology];Electrocardiography;Ischemic Attack, Transient [drug therapy] [therapy];Ischemic Preconditioning [adverse effects] [methods];Magnetic Resonance Imaging;Risk Assessment;Risk Factors;Salvage Therapy;Stroke [drug therapy] [therapy];Thrombolytic Therapy [methods];Treatment Outcome;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Hougaard, K. D.;Hjort, N.;Zeidler, D.;Sørensen, L.;Nørgaard, A.;Hansen, T. M.;Weitzel-Mudersbach, P.;Simonsen, C. Z.;Damgaard, D.;Gottrup, H.;Svendsen, K.;Rasmussen, P. V.;Ribe, L. R.;Mikkelsen, I. K.;Nagenthiraja, K.;Cho, T. H.;Redington, A. N.;Bøtker, H. E.;Østergaard, L.;Mouridsen, K.;Andersen, G.",2014,,,0,
3796,Mesiotemporal atrophy and hippocampal diffusivity distinguish amnestic from non-amnestic vascular cognitive impairment,"BACKGROUND AND PURPOSE: The role of clinical factors, cerebral infarcts and hippocampal damage in vascular cognitive impairment (VCI) subtypes remains unclear. METHODS: Non-demented patients with carotid stenosis and recent transient ischemic attack/stroke had cognitive assessment and brain magnetic resonance imaging (MRI). Amnestic VCI was defined as memory impairment; non-amnestic VCI was any other subdomain impairment. Associations of MRI metrics [log-transformed total ischemic lesion load (log TILL), mesiotemporal atrophy (MTA) score, hippocampal mean diffusivity (hipMD)] with cognitive performance were assessed. RESULTS: A hundred and eight patients, 47 with amnestic VCI and 21 with non-amnestic VCI, were assessed. A higher MTA (odds ratio 12.89, P = 0.001) and left hipMD (odds ratio 4.43, P = 0.003) contributed to amnestic VCI versus normal. Age-adjusted fluency correlated with log TILL (P = 0.002). Age-adjusted memory was associated with left hipMD (P = 0.001), MTA (P < 0.001) but not log TILL (P = 0.14). Left hipMD, MTA and smoking showed classification potential between amnestic VCI versus normal (area 0.859, P < 0.001). CONCLUSIONS: Neuroimaging assists stratification in amnestic VCI characterized by hippocampal changes and in non-amnestic VCI by higher ischemic burden. MTA and hippocampal diffusivity show diagnostic biomarker potential.",hippocampus;magnetic resonance imaging;mild cognitive impairment;stroke;vascular dementia,"Hosseini, A. A.;Meng, D.;Simpson, R. J.;Auer, D. P.",2017,Jul,,0,
3797,Performance of 11C-pittsburgh compound B PET binding potential images in the detection of amyloid deposits on equivocal static images,"The goal of this study was to clarify whether binding potential (BP) images using (11)C-Pittsburgh compound B ((11)C-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose (11)C-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. Methods: Static and BP images were constructed for 85 consecutive patients with cognitive impairment after (11)C-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)CPiB- negative groups. Results: Forty-three scans were visually assessed as (11)C-PiB-positive in both the static and the BP images. Ten scans were (11)C-PiB-equivocal in the static images. In 8 of them, the BP images were (11)C-PiB-positive, whereas the other 2 were (11)C-PiB-equivocal. Thirty-two scans were assessed as (11)CPiB- negative in the static images. In the BP images, 4 were (11)CPiB- positive and 2 were (11)C-PiB-equivocal. The mean gray matter uptake of (11)C-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the (11)C-PiB- positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the (11)C-PiB-negative and (11)C-PiB- equivocal groups, whereas it was higher in the (11)C-PiB-positive group. Conclusion: (11)C-PiB PET BP images can clarify visual interpretation of clinical static (11)C-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that (11)C-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings.",,"Hosokawa, C.;Ishii, K.;Kimura, Y.;Hyodo, T.;Hosono, M.;Sakaguchi, K.;Usami, K.;Shimamoto, K.;Yamazoe, Y.;Murakami, T.",2015,1,,0,
3798,MM1-type sporadic Creutzfeldt-Jakob disease with unusually prolonged disease duration presenting with panencephalopathic-type pathology,"We report an autopsy case of MM1-type sporadic Creutzfeldt-Jakob disease (sCJD) with an unusually prolonged disease duration of 58 months. The initial symptom was progressive mental disorder followed by advanced cognitive impairment. Clinical progression was generally slow; myoclonus appeared at 17 months and periodic sharp-wave complexes on electroencephalogram at 21 months. A state of akinetic mutism occurred 29 months after the onset of symptoms. MRI showed gradually progressive cerebral atrophy. Neuropathologic examination showed widespread severe brain involvement. In the cerebral neocortex, widespread severe tissue rarefaction, hypertrophic astrocytosis and neuron loss (so-called status spongiosus) were observed. The cerebral white matter showed diffuse myelin pallor with intense hypertrophic astrocytosis, numerous foamy macrophages and emperipolesis, indicating panencephalopathic-type sCJD pathology. The brainstem was relatively preserved from sCJD pathology, with the exception of the pontine nucleus and pyramidal tract. This may explain the prolonged disease duration without respiratory insufficiency until the terminal stage. Immunohistochemistry for prion protein (PrP) showed widespread synaptic-type PrP deposits in the cerebral neocortex, hippocampus and thalamus. The striatum and cerebellar cortex showed faint synaptic-type PrP deposition with some areas of small plaque-like PrP deposition. Sparse PrP deposition was also observed in the brainstem. Analysis of the PrP gene showed no mutation but methionine homozygosity at polymorphic codon 129. Western blot analysis of protease-resistant PrP indicated type 1 PrP. To our knowledge, this is the longest reported disease duration of MM1-type sCJD. © 2008 Japanese Society of Neuropathology.",prion protein;adult;article;autopsy;brain stem;case report;clinical feature;Creutzfeldt Jakob disease;disease duration;female;histopathology;human;human tissue;nuclear magnetic resonance imaging;priority journal;white matter,"Hoshino, A.;Iwasaki, Y.;Izumi, M.;Kimura, S.;Ibi, T.;Kitamoto, T.;Yoshida, M.;Hashizume, Y.;Sahashi, K.",2008,,,0,
3799,Quantitative (1)H MR spectroscopic imaging in early Rett syndrome,"Objective: To determine cerebral regional concentrations of N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cr) in Rett syndrome (RS) using (1)H magnetic resonance spectroscopic imaging (MRSI). Background: The biochemical defect underlying RS is unknown. Because in vivo MRSI can detect important cerebral metabolites, MRSI has a potential to reveal impairment of regional cerebral metabolism in RS noninvasively. Methods: High-resolution, multislice (1)H MRSI was carried out in 17 girls with RS. The control group consisted of nine healthy children. Results: In patients with RS, average Cho concentration was 12% higher (p < 0.005) and average NAA concentration 11% lower (p < 0.0001) compared with the control group. Regional metabolic differences included significantly lower NAA concentration in the frontal gray and white matter, insula, and hippocampus in RS; no difference in regional Cho and Cr concentrations were found. A 20 to 38% higher Cho:NAA ratio in frontal and parietal gray and white matter, insular gray matter, and hippocampus (p < 0.05) and a 14 to 47% lower NAA:Cr ratio in frontal cortical gray matter, parietal and temporal white matter, insula, and putamen (p < 0.05) were found in subjects with RS compared with controls. Patients with seizures had higher average concentrations of Cho, Cr, and NAA compared with those without seizures (8-19%, p < 0.05). Conclusion: Metabolic impairment in RS involves both gray and white matter and particularly involves frontal and parietal lobes and the insular cortex. Loss of NAA most likely reflects reduced neuronal and dendritic tree size; increased Cho concentration may result from gliosis.",,"Horská, A.;Naidu, S.;Herskovits, E. H.;Wang, P. Y.;Kaufmann, W. E.;Barker, P. B.",2000,8,,0,
3800,In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer's disease,"Behavioural variant frontotemporal dementia can present with episodic memory deficits as severe as those in Alzheimer's disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant frontotemporal dementia and Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant frontotemporal dementia and Alzheimer's disease show similar degrees of hippocampal atrophy in vivo, but patients with behavioural variant frontotemporal dementia show greater hippocampal atrophy at post-mortem, with the frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant frontotemporal dementia being affected more anteriorly and Alzheimer's disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant frontotemporal dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant frontotemporal dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant frontotemporal dementia or Alzheimer's disease pathology, although for behavioural variant frontotemporal dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant frontotemporal dementia and Alzheimer's disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant frontotemporal dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant frontotemporal dementia or Alzheimer's disease pathology.","Aged;Alzheimer Disease/ pathology;Cause of Death;Female;Frontotemporal Dementia/ pathology;Hippocampus/ pathology/physiopathology;Humans;Male;Memory Disorders/ pathology;Memory, Episodic;Middle Aged;Nerve Net/pathology","Hornberger, M.;Wong, S.;Tan, R.;Irish, M.;Piguet, O.;Kril, J.;Hodges, J. R.;Halliday, G.",2012,Oct,10.1093/brain/aws239,0,
3801,Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia,"Disinhibition is a common behavioural symptom in frontotemporal dementia but its neural correlates are still debated. In the current study, we investigated the grey and white matter neural correlates of disinhibition in a sample of behavioural variant frontotemporal dementia (n = 14) and patients with Alzheimer's disease (n = 15). We employed an objective (Hayling Test of inhibitory functioning) and subjective/carer-based (Neuropsychiatric Inventory) measure of disinhibition to reveal convergent evidence of disinhibitory behaviour. Mean and overlap-based statistical analyses were conducted to investigate profiles of performance in patients with behavioural variant frontotemporal dementia, Alzheimer's disease and controls. Hayling Test and Neuropsychiatric Inventory scores were entered as covariates in a grey matter voxel-based morphometry, as well as in a white matter diffusion tensor imaging analysis to determine the underlying grey and white matter correlates. Patients with behavioural variant frontotemporal dementia showed more disinhibition on both behavioural measures in comparison to patients with Alzheimer's disease and controls. Voxel-based morphometry results revealed that atrophy in orbitofrontal/subgenual, medial prefrontal cortex and anterior temporal lobe areas covaried with total errors score of the Hayling Test. Similarly, the Neuropsychiatric Inventory disinhibition frequency score correlated with atrophy in orbitofrontal cortex and temporal pole brain regions. The orbitofrontal atrophy related to the objective (Hayling Test) and subjective (Neuropsychiatric Inventory) measures of disinhibition was partially overlapping. Diffusion tensor imaging analysis revealed that white matter integrity fractional anisotropy values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated well with the total error score of the Hayling Test. Our results show that a network of orbitofrontal, anterior temporal and mesial frontal brain regions and their connecting white matter tracts are involved in inhibitory functioning. Further, we find convergent evidence for objective and subjective disinhibition measures that the orbitofrontal/subgenual brain region is critical for adapting and maintaining normal behaviour.","Aged;Behavior/physiology;Behavioral Symptoms/ physiopathology;Diffusion Tensor Imaging;Female;Frontal Lobe/ pathology/ physiopathology;Frontotemporal Dementia/ pathology/ physiopathology;Humans;Inhibition (Psychology);Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Hornberger, M.;Geng, J.;Hodges, J. R.",2011,Sep,10.1093/brain/awr173,0,
3802,Atrophy of hippocampus in patients with Alzheimer's disease and other diseases with memory impairment,"In clinical practice, Alzheimer's disease (AD), multi-infarct Dementia (MID) and depression are often difficult to differentiate and may coexist. This study reports the findings of CT and MRI focused on hippocampal atrophy (HA). Quantitative volumetric MRI measurements of the hippocampus showed a reduced volume in AD patients compared to normal controls with no overlap. CT studies reported a significant widening of the hippocampal fissure in AD patients. Because volumetric measurements are not available for routine examinations, so far we are required to use the finding of hippocampal lucency in CT and dilatation of the directly visible hippocampal fissure in coronal MRI scans as criteria for HA. These findings were visually classified on a 4-point scale by 2 neuroradiologists, who had no knowledge of the clinical diagnosis. The examinations of 80 patients (42 with AD, 22 with major depression, 3 with MID, 6 classified as age-associated memory impairment (AAMI) and 8 'normals' with only subjective memory impairment) showed that the HA stronlgy supports the diagnosis of AD, by correctly identifying 95% of the AD patients and 47.8% of the patients without AD. These results suggest that CT and MRI examinations of the hippocampus are capable of demonstrating HA in clinical practice, which is strongly correlated with the diagnosis of AD.",adult;aged;Alzheimer disease;amnesia;article;brain atrophy;clinical trial;computer assisted tomography;controlled clinical trial;controlled study;depression;female;hippocampus;human;major clinical study;male;neuroradiology;nuclear magnetic resonance imaging;priority journal,"Horn, R.;Ostertim, B.;Fric, M.;Solymosi, L.;Steudel, A.;Möller, H. J.",1996,,,0,
3803,Difference in white matter microstructure in differential diagnosis of normal pressure hydrocephalus and Alzheimer's disease,"OBJECTIVES: Alzheimer's disease (AD) and normal pressure hydrocephalus (NPH) are both associated with cognitive decline and ventriculomegaly. While promising approach in differentiating between the two diseases, only a few diffusion tensor imaging (DTI) studies compared directly NPH and AD patients. The current study compares global whitematter (WM) alterations in AD and NPH addressing some of the methodological issues of previous studies. PATIENTS AND METHODS: Diffusion tensor images were obtained from 17 patients with NPH, 14 with AD, and 17 healthy controls. White matter integrity was quantified by fractional anisotropy (FA), mean (MD), axial (lambda1) and radial diffusivity (RD). The diffusion parameters were compared between the groups in 'skeletonised' tracts representing the core of the fibre bundles. RESULTS: Reduced FA was found in NPH patients throughout the corpus callosum, particularly in the splenium, along with increased RD. On the other hand, FA, MD and RD were higher in NPH in the cortico-fugal fibres arising from the frontal and parietal cortex. While no FA changes were detected in AD patients compared to controls, widespread increased RD was observed. When comparing NPH and AD patients, higher FA, MD and RD was observed in the corona radiata in the periventricular fibres arising from the frontal and parietal cortex in NPH patients. The ventricular volumes were correlated with diffusivity parameters in the tracts next to the ventricles in AD and NPH patients. CONCLUSION: Our analysis identified a pattern of WM diffusion alterations that can differentiate NPH patients from controls and AD patients.",,"Horinek, D.;Stepan-Buksakowska, I.;Szabo, N.;Erickson, B. J.;Toth, E.;Sulc, V.;Benes, V.;Vrana, J.;Hort, J.;Nimsky, C.;Mohapl, M.;Rocek, M.;Vecsei, L.;Kincses, Z. T.",2016,Jan,10.1016/j.clineuro.2015.11.010,0,
3804,Risk of falls in Alzheimer's disease: a prospective study,"OBJECTIVE: Falls are common in patients with Alzheimer's disease (AD). Identification of the potential risk factors and developing preventive strategies for falls will have a significant impact in maintaining the quality of life in AD. PATIENTS: Clinical follow-up of 124 (74.1+/-6.1 years, range 62-88) mild to moderate AD patients in an outpatient memory clinic. METHODS: Postural sway, cognitive function, use of neuroleptics, severity of periventricular and deep white matter lesions, and the presence or absence of silent brain infarctions on magnetic resonance imaging were assessed at baseline. RESULTS: A total of 104 patients (84%) completed the study. Fall events were confirmed in 42.3% (44/104). After adjustment for age, gender, and cognitive status, a high grade of periventricular white matter lesions (odds ratio 8.7 [95%CI 1.5 to 51.8], p = 0.017) and neuroleptic drug use (odds ratio 3.5 [95%CI 1.2 to 10.5], p = 0.027) were significantly associated with an increased risk of falls. CONCLUSION: Our results suggest that periventricular white matter lesions and the use of neuroleptics may be related to falls in mild to moderate AD. A comprehensive risk management of brain ischemia as well as the use of the smallest efficacious dose of neuroleptics in the treatment of behavioral and psychiatric symptoms of AD should be recommended to help reduce the risk of unexpected falls.","Accidental Falls/prevention & control/ statistics & numerical data;Aged;Aged, 80 and over;Alzheimer Disease/complications/ epidemiology;Antipsychotic Agents/therapeutic use;Female;Humans;Magnetic Resonance Imaging;Male;Prospective Studies;Quality of Life","Horikawa, E.;Matsui, T.;Arai, H.;Seki, T.;Iwasaki, K.;Sasaki, H.",2005,Jul,,0,
3805,Prevalence of white matter hyperintensities in a young healthy population,"Background and Purpose. White matter hyperintensities (WMHs) are bright objects observed in the white matter on brain magnetic resonance (MR) imaging. WMHs are often reported as ""normal"" findings but may represent pathological changes. The prevalence of WMHs appears to increase with increasing age although both the typical timing and clinical significance of their appearance among medically and neurologically healthy persons remains unclear. We assessed the prevalence of WMHs in a cohort of younger healthy subjects. Methods. Our study comprised 243 healthy subjects ages 16-65 years from our prospective normative MR imaging database. MR scans were rated for presence of periventricular and centrum semiovale WMHs using a four-point visual semi-quantitative scale. Results. WMHs occurred in 5.3% (13 of 243) of subjects. All WMHs were small (rating of 0.5) except one subject age 65 years who had large WMHs (ratings of 2). The median age for subjects with no WMHs was 34.5 years compared to 57.0 years for subjects with WMHs. There were no gender differences (P =.76). Older age correlated with presence of WMHs (r = 0.24; P =.01). Age greater than 55 years had a 10-fold increase in the prevalence of WMHs compared to age ≤55 years (odds ratio = 10.01; 95% confidence interval = 3.1-32.3; P <.001). Conclusion. WMHs were uncommon in a younger healthy population screened for comorbid diseases, but increased 10-fold in subjects over 55 years of age. When present, the WMHs are generally small (rating of 0.5). While large WMHs appear to be associated with cognitive deterioration, the optimum threshold for identification, clinical significance, and prognostic value of smaller white matter changes requires further research. © 2006 by the American Society of Neuroimaging.",,"Hopkins, R. O.;Beck, C. J.;Burnett, D. L.;Weaver, L. K.;Victoroff, J.;Bigler, E. D.",2006,July,,0,
3806,"Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study","Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged >/=85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-beta and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and alpha-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-beta accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or alpha-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged >/=85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.","Aged, 80 and over;Alzheimer Disease/ blood;Apolipoproteins E/genetics;Cerebral Amyloid Angiopathy/metabolism/pathology;Cerebrovascular Disorders/ blood;Community Health Planning;Diagnosis;Female;Homocysteine/ blood;Humans;Magnetic Resonance Imaging;Male;Neurofibrillary Tangles/pathology;Plaque, Amyloid/pathology;alpha-Synuclein/metabolism","Hooshmand, B.;Polvikoski, T.;Kivipelto, M.;Tanskanen, M.;Myllykangas, L.;Erkinjuntti, T.;Makela, M.;Oinas, M.;Paetau, A.;Scheltens, P.;van Straaten, E. C.;Sulkava, R.;Solomon, A.",2013,Sep,10.1093/brain/awt206,0,
3807,"Association of Vitamin B12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults: A Longitudinal Population-Based Study","Importance: Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. Objective: To investigate the association of circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. Design, Setting, and Participants: The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. Main Outcomes and Measures: The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. Results: In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, beta (SE) was 0.048 (0.013) for vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (beta [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140 mm Hg (beta [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. Conclusions and Relevance: This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults.",,"Hooshmand, B.;Mangialasche, F.;Kalpouzos, G.;Solomon, A.;Kareholt, I.;Smith, D.;Refsum, H.;Wang, R.;Muhlmann, M.;Ertl-Wagner, B.;Laukka, E. J.;Backman, L.;Fratiglioni, L.;Kivipelto, M.",2016,Apr 27,10.1001/jamapsychiatry.2016.0274,0,
3808,"Association of Vitamin B12, folate, and sulfur amino acids with brain magnetic resonance imaging measures in older adults a longitudinal population-based study","Importance: Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. Objective: To investigate the association of circulating levels of Vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. Design, Setting, and Participants: Themagnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. Main Outcomes and Measures: The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. Results: In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline Vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, β (SE) was 0.048 (0.013) for Vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (β [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140mmHg (β [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. Conclusions and Relevance: This study suggests that both Vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of Vitamin B12 supplementation on slowing brain aging in older adults.",creatinine;cyanocobalamin;cystathionine;cysteine;folic acid;glutathione;homocysteine;methionine;sulfur amino acid;aged;article;brain atrophy;brain level;brain size;brain tissue;cerebrospinal fluid;controlled study;disease association;erythrocyte level;female;fluid attenuated inversion recovery;follow up;glomerulus filtration rate;human;imaging and display;longitudinal study;major clinical study;male;nuclear magnetic resonance imaging;prospective study;Sweden;systolic blood pressure;very elderly;white matter,"Hooshmand, B.;Mangialasche, F.;Kalpouzos, G.;Solomon, A.;Kareholt, I.;Smith, A. D.;Refsum, H.;Wang, R.;Muhlmann, M.;Ertl-Wagner, B.;Laukka, E. J.;Backman, L.;Fratiglioni, L.;Kivipelto, M.",2016,,10.1001/jamapsychiatry.2016.0274,0,
3809,"Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes","BACKGROUND: Low vitamin D status is associated with poorer cognitive function in older adults, but little is known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain tissue volumes. METHODS: A total of 75 patients (29 with subjective cognitive impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma 25(OH)D, CSF levels of amyloid beta (Abeta(1-42)), total-tau, and phosphorylated tau, and brain tissue volumes have been measured. RESULTS: After adjustment for several potential confounders, the odds ratios (95% confidence interval) for cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1 nmol/L of 25(OH)D and 4.19 (1.30-13.52) for 24(OH)D values less than 50 nmol/L compared with values greater than or equal to 50 nmol/L. Adjusting for CSF Abeta(1-42) attenuated the 25(OH)D-cognition link. In a multiple linear regression analysis, higher 25(OH)D levels were related to higher concentrations of CSF Abeta(1-42) and greater brain volumes (eg, white matter, structures belonging to medial temporal lobe). The associations between 25(OH)D and tau variables were not significant. CONCLUSIONS: This study suggests that vitamin D may be associated with cognitive status, CSF Abeta(1-42) levels, and brain tissue volumes.",Alzheimer Disease/cerebrospinal fluid;Amyloid beta-Peptides/*cerebrospinal fluid;Biomarkers/*cerebrospinal fluid;Brain/*anatomy & histology;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/cerebrospinal fluid;Organ Size;Peptide Fragments/*cerebrospinal fluid;Vitamin D/*analogs & derivatives/blood;tau Proteins/cerebrospinal fluid;CSF biomarkers;Cognition;Mri.;Older adults;Vitamin D,"Hooshmand, B.;Lokk, J.;Solomon, A.;Mangialasche, F.;Miralbell, J.;Spulber, G.;Annerbo, S.;Andreasen, N.;Winblad, B.;Cedazo-Minguez, A.;Wahlund, L. O.;Kivipelto, M.",2014,Sep,10.1093/gerona/glu022,0,
3810,Single photon emission computed tomography (SPECT) versus clinical assessment in the evaluation of dementia,"Seventy-two hospitalized psychogeriatric patients, with an average age of 73 years, were classified into 3 diagnostic categories. There were 20 patients with dementia of the Alzheimer type (DAT), 29 patients with vascular dementia (primarily multiple infarct dementia, MID), and 23 patients with various other psychiatric diagnoses. Patients were assessed by computed tomography (CT) and single photon emission computed tomography (SPECT). No specific correspondence between the SPECT results and the clinical diagnoses were found. The bilateral parietal-occipital pattern, typical of DAT, was found in only one DAT subject. CT and SPECT were equivalently sensitive in finding brain pathology, but both CT and SPECT appear to have little value in differential diagnosis in psychogeriatric patients outside of documenting the site and severity of the brain pathology. The most reliable method of diagnosis for dementia, particularly the Alzheimer type, appears to be the standard clinical assessment.",adult;aged;Alzheimer disease;article;computer assisted tomography;degenerative disease;diagnostic accuracy;female;human;major clinical study;male;multiinfarct dementia;neuropathology;neuroradiology;single photon emission computer tomography,"Hontela, S.;Tomat, D. L.;Reddon, J. R.;Pilisko, J. D.",1996,,,0,
3811,Event-related potential P300 in multiple sclerosis. Relation to magnetic resonance imaging and cognitive impairment,"Cerebral involvement in multiple sclerosis may result not only in sensory and motor symptoms but also in impaired mentation. We hypothesize that cognitive dysfunction occurs due to cortical deafferentation or disconnection arising from subcortical white-matter disease. We examined the P300 event-related potential in 31 patients with multiple sclerosis, correlating it with disease severity ratings based on magnetic resonance imaging signal intensity changes, cognitive dysfunction, and disability status. The patients with multiple sclerosis exhibited significantly prolonged P300 wave latencies compared with 32 control subjects. The P300 latency was strongly correlated with the presence of demyelinative brain lesions seen on magnetic resonance imaging scans and with cognitive impairment, but was only weakly associated with the Kurtzke disability status score, consistent with this scale primarily reflecting spinal rather than cerebral demyelination. Our study results support a relationship between subcortical white-matter lesions and cognitive impairment in multiple sclerosis.",Adult;Brain/ physiopathology;Cognition Disorders/physiopathology;Dementia/physiopathology;Electroencephalography;Evoked Potentials;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multiple Sclerosis/pathology/ physiopathology,"Honig, L. S.;Ramsay, R. E.;Sheremata, W. A.",1992,Jan,,0,
3812,Do Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) progress differently?,"Our study aimed to compare cognitive status and declines in AD with/without small vessel disease (SVD) and SIVD at baseline and 1-year follow-up. Patients with Alzheimer's disease without small vessel disease (AD(-)SVD) (n=148), Alzheimer's disease with small vessel disease (AD(+)SVD) (n=94) and SIVD (n=60) were recruited from database of multiple centers in Korea. Basic demographics and detailed neuropsychological results were compared. AD, regardless of SVD, showed worse memory and better executive function than SIVD at baseline. Mini-Mental State Examination scores and visual memory function declined more in AD than those in SIVD whereas Barthel Activities of Daily Living (B-ADL) scores declined more in SIVD. AD showed different patterns of cognitive impairment compared with SIVD. After 1 year, AD showed more rapid cognitive decline in some domains. Further investigations with longer follow-up duration may be needed to confirm the cumulative effects of SVD in AD and different patterns of decline between AD and SIVD.","Aged;Aged, 80 and over;Alzheimer Disease/*physiopathology/psychology;Cognition/*physiology;Cognition Disorders/etiology/*physiopathology/psychology;Dementia, Vascular/*physiopathology/psychology;*Disease Progression;Executive Function;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Neuropsychological Tests;Republic of Korea;Ad;Cognitive neuropsychology;Disease progression;Sivd;Svd","Hong, Y. J.;Yoon, B.;Shim, Y. S.;Han, I. W.;Han, S. H.;Park, K. H.;Choi, S. H.;Ku, B. D.;Yang, D. W.",2014,May-Jun,10.1016/j.archger.2013.11.005,0,
3813,Gray and White Matter Degenerations in Subjective Memory Impairment: Comparisons with Normal Controls and Mild Cognitive Impairment,"Subjective memory impairment (SMI) is now increasingly recognized as a risk factor of progression to dementia. This study investigated gray and white matter changes in the brains of SMI patients compared with normal controls and mild cognitive impairment (MCI) patients. We recruited 28 normal controls, 28 subjects with SMI, and 29 patients with MCI aged 60 or older. We analyzed gray and white matter changes using a voxel-based morphometry (VBM), hippocampal volumetry and regions of interest in diffusion tensor imaging (DTI). DTI parameters of corpus callosum and cingulum in SMI showed more white matter changes compared with those in normal controls, they were similar to those in MCI except in the hippocampus, which showed more degenerations in MCI. In VBM, SMI showed atrophy in the frontal, temporal, and parietal lobes compared with normal controls although it was not as extensive as that in MCI. Patients with SMI showed gray and white matter degenerations, the changes were distinct in white matter structures. SMI might be the first presenting symptom within the Alzheimer's disease continuum when combined with additional risk factors and neurodegenerative changes.",,"Hong, Y. J.;Yoon, B.;Shim, Y. S.;Ahn, K. J.;Yang, D. W.;Lee, J. H.",2015,Nov,10.3346/jkms.2015.30.11.1652,0,
3814,Microstructural changes in the hippocampus and posterior cingulate in mild cognitive impairment and Alzheimer's disease: a diffusion tensor imaging study,"Diffusion tensor imaging (DTI) is a sensitive MRI technique in the detection of white matter degeneration. We sought to demonstrate microstructural changes in normal controls, patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) and to determine which DTI parameters could be a reliable tool for the early diagnosis of AD. In total, 90 participants (35 normal, 20 aMCI, 35 AD) were recruited. We included early AD patients with clinical dementia rating scores of 0.5 and 1. The fractional anisotropy and mean diffusivity values, DTI parameter, were measured with the regions of interest method in the bilateral hippocampal body and posterior cingulate. Clinical history, neurological examination, and neuropsychological assessments were conducted. The DTI parameters in the bilateral hippocampus and posterior cingulate in aMCI and AD were different from those in normal controls. No difference was found in DTI parameters of the posterior cingulate between aMCI and AD. However, hippocampal DTI parameters were different between aMCI and AD. Cognitive summary measures were significantly correlated with DTI parameters, especially FA values in the hippocampus. The DTI analysis technique demonstrated significant microstructural alterations in the hippocampus and posterior cingulate already in prodromal stage of AD. DTI parameters in the hippocampus may be a more sensitive method to determine microstructural changes in early AD states and more correlated with cognition than DTI parameters in the posterior cingulate.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/metabolism;Cross-Sectional Studies;Diffusion Tensor Imaging/ methods;Female;Gyrus Cinguli/ pathology;Hippocampus/ pathology;Humans;Male;Mild Cognitive Impairment/ diagnosis/metabolism","Hong, Y. J.;Yoon, B.;Lim, S. C.;Shim, Y. S.;Kim, J. Y.;Ahn, K. J.;Han, I. W.;Yang, D. W.",2013,Jul,10.1007/s10072-012-1225-4,0,
3815,Regional amyloid burden and lacune in pure subcortical vascular cognitive impairment,"We investigated the amyloid and vascular burden in Pittsburgh compound B (PiB)-negative subcortical vascular mild cognitive impairment (svMCI) and PiB-negative subcortical ischemic vascular dementia (SIVD) to elucidate the potential roles of amyloid deposition and small vessel disease (SVD). Thirty-eight svMCI patients and 42 SIVD patients were enrolled. The regional PiB uptake values and SVD markers were obtained and compared between groups. Additionally, correlations among amyloid burden, SVD, and cognition were made. Patients with PiB-negative SIVD showed more amyloid deposition than those with PiB-negative svMCI, particularly in the cuneus, lingual gyrus, supramarginal, and angular gyri. Despite subthreshold levels for amyloid deposition, our findings showed a marked regional difference in amyloid uptake between svMCI and SIVD, particularly in posteriorly located brain areas. However, lacune, a proxy for vascular burden, showed a broader association with cognition and had more impacts on developing dementia than amyloid burden. The topographical pattern of amyloid deposition and its impact on clinical status in pure subcortical vascular cognitive impairment were different from those in Alzheimer's disease.","0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole);0 (Amyloidogenic Proteins);0 (Aniline Compounds);0 (Thiazoles);Aged;Aged, 80 and over;Amyloidogenic Proteins/ metabolism;Aniline Compounds;Brain/diagnostic imaging/ metabolism;Brain Mapping;Cerebral Small Vessel Diseases/complications;Cognition;Cognitive Dysfunction/diagnosis/diagnostic imaging/ etiology/psychology;Dementia, Vascular/diagnosis/diagnostic imaging/ etiology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuroimaging;Thiazoles;Tomography, X-Ray Computed;Amyloid;Cerebral small vessel disease;Pittsburgh compound B;Subcortical ischemic vascular dementia;Subcortical vascular mild cognitive impairment;Vascular cognitive impairment","Hong, Y. J.;Kim, C. M.;Kim, J. E.;Roh, J. H.;Kim, J. S.;Seo, S. W.;Na, D. L.;Lee, J. H.",2017,Jul,,0,
3816,White matter changes may precede gray matter loss in elderly with subjective memory impairment,"Background/Aims: A limited number of studies addressed MRI-based neurodegenerative changes in subjective memory impairment (SMI). We investigated changes in white matter (WM) microstructures as well as gray matter (GM) macrostructures in subjects with SMI of high and low risk for progression. Methods: A modeling scale (score range, 0-6) developed for prediction of SMI progression was used to divide SMI subjects (n = 46) into two groups: a high risk of progression (score ≥3; n = 19) and a low risk of progression (score ≤2; n = 27). Cross-sectional comparisons were performed using a region-of-interest-based diffusion tensor imaging (DTI) analysis, cortical thickness analysis, and hippocampal volumetry. Results: The high-risk group had more microstructural disruption shown by lower fractional anisotropy in the hippocampus, parahippocampal gyrus, supramarginal gyrus, and parts of frontotemporal lobes. On the other hand, GM macrostructural changes did not differ between the groups and were not associated with modeling scale scores. Conclusion: SMI subjects with a high risk of progression had more WM microstructural disruption than those with a low risk, and the changes were not explained by GM atrophy. Our findings suggest that the degree of microstructural alterations in SMI may be distinctive according to the risk factors and may precede GM atrophy.",adjustment;adult;age;article;clinical assessment;controlled study;cuneus;diffusion tensor imaging;female;fractional anisotropy;gray matter;high risk population;hippocampus;human;learning;low risk population;major clinical study;male;memory disorder;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;parahippocampal gyrus;posterior cingulate;precuneus;prediction;priority journal;supramarginal gyrus;white matter,"Hong, Y. J.;Kim, C. M.;Jang, E. H.;Hwang, J.;Roh, J. H.;Lee, J. H.",2016,,10.1159/000450749,0,
3817,Impact of APOE on the healthy aging brain: a voxel-based MRI and DTI study,"Neuroimaging studies of apolipoprotein E (ApoE4) have implicated its association with brain atrophy in Alzheimer's disease. To date, few studies have used automated morphological analysis techniques to assess ApoE4-related brain structure change in both gray and white matter in nondemented older adults. Nondemented (CDR = 0, n = 53) subjects over 60 had MRI, diffusion tensor imaging, and neurocognitive assessments. We assessed differences in cognition and brain structure associated with ApoE4 genetic variation using voxel-based morphometry techniques, and tract-based spatial statistics of fractional anisotropy change. In nondemented older adults with the E4 allele, cognitive performance was reduced, and atrophy was present in the hippocampus and amygdala compared to ApoE4 negative participants. We also report that E4 carriers have decreased fractional anisotropy in the left parahippocampal gyrus white matter. In conclusion, the presence of an ApoE4 allele in nondemented older adults is associated with decreases in cognition and gray and white matter changes in the medial temporal cortex. Overall we provide further evidence of the effects of genetic variance related to imaging and cognitive measures of risk for Alzheimer's disease.",Activities of Daily Living;Aged;Aging/ physiology;Alzheimer Disease/genetics/physiopathology;Amygdala/physiopathology;Anisotropy;Apolipoprotein E4/ genetics;Brain/ physiology/physiopathology;Diffusion Tensor Imaging;Female;Genotype;Health Status;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Motor Activity;Parahippocampal Gyrus/physiopathology;Surveys and Questionnaires,"Honea, R. A.;Vidoni, E.;Harsha, A.;Burns, J. M.",2009,,10.3233/jad-2009-1163,0,
3818,Interobserver variation in diagnosis of dementia by brain perfusion SPECT,"Brain perfusion SPECT (BP-SPECT) has characteristic patterns of abnormality, enabling the differential diagnosis of dementia. The purpose of this study was to measure interobserver variations in the diagnosis of dementia using",,"Honda, N.;Machida, K.;Hosono, M.;Matsumoto, T.;Matsuda, H.;Oshima, M.;Koizumi, K.;Kosuda, S.;Momose, T.;Mori, Y.;Hashimoto, J.;Shimizu, Y.",2002,November/December,,0,
3819,Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy,"BACKGROUND: An impairment of amyloid-beta (Abeta) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. OBJECTIVE: This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). METHODS: Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. RESULTS: Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. CONCLUSION: In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.","Adult;Aged;Aged, 80 and over;Brain/ diagnostic imaging;Carotid Artery Diseases/complications/ diagnostic imaging/epidemiology;Cerebral Amyloid Angiopathy/complications/ diagnostic imaging/epidemiology;Cerebral Angiography;Cerebral Hemorrhage/complications/ diagnostic imaging/epidemiology;Female;Humans;Infarction, Middle Cerebral Artery/complications/ diagnostic imaging/epidemiology;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Middle Aged;Prevalence;Alzheimer's disease;carotid occlusion;cerebral amyloid angiopathy;cortical microbleeds;perivascular drainage","Honda, K.",2016,Aug 1,,0,
3820,[Clinical correlation of vascular parkinsonism] Korelacje kliniczne parkinsonizmu naczyniowego,"Vascular parkinsonism has not been well defined and the clinical correlation of vascular parkinsonism is still not clear. The aim of the study was to estimate prevalence of occurrence of vascular parkinsonism, analysis of risk factors leading to its development and to identify clinical features that suggest a vascular origin. 214 patients with Parkinson's disease were examined. Their ages ranged from 37 to 88 years (median 66.4 years). Evidence of vascular parkinsonism was assessed using a vascular rating scale previously described by Winikates and Jankovic. Statistical analysis was performed with Mann-Whitney U test, chi 2 Pearson test, chi 2 Yates test, Spearman rank correlation and Student's t test. Out of 214 patients 8 were proved to have developed Parkinson's disease due to vascular disease, what gave 3.74%. Out of risk factors for stroke 5 patients had hypertension, 3 had diabetes mellitus, 2 suffered from heart disease, 2 had infarctus myocardii, 1 had hyperlipidemia, 1 had atrial fibrillation. Additionally, those patients had neuroimaging (CT or MRI) evidence of vascular disease in one or more vascular territories. Patients with vascular parkinsonism were older, had shorter duration of disease, were more likely to present rigidity rather than tremor. Dementia and incontinence were more common in vascular group than in Parkinson's disease group. Patients with vascular parkinsonism were also significantly more likely to have corticospinal findings. Proving that Parkinson's disease had vascular etiology is extremely difficult. The test results are inconclusive.","Adult;Aged;Aged, 80 and over;Brain/ blood supply/diagnostic imaging/pathology;Cerebrovascular Circulation/physiology;Dementia/diagnosis/epidemiology;Female;Humans;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Parkinsonian Disorders/diagnosis/epidemiology/ physiopathology;Prevalence;Risk Factors;Tomography, X-Ray Computed;Urinary Incontinence/diagnosis/epidemiology","Honczarenko, K.;Budzianowska, A.",2003,,,0,
3821,[Clinical correlation of vascular parkinsonism],"Vascular parkinsonism has not been well defined and the clinical correlation of vascular parkinsonism is still not clear. The aim of the study was to estimate prevalence of occurrence of vascular parkinsonism, analysis of risk factors leading to its development and to identify clinical features that suggest a vascular origin. 214 patients with Parkinson's disease were examined. Their ages ranged from 37 to 88 years (median 66.4 years). Evidence of vascular parkinsonism was assessed using a vascular rating scale previously described by Winikates and Jankovic. Statistical analysis was performed with Mann-Whitney U test, chi 2 Pearson test, chi 2 Yates test, Spearman rank correlation and Student's t test. Out of 214 patients 8 were proved to have developed Parkinson's disease due to vascular disease, what gave 3.74%. Out of risk factors for stroke 5 patients had hypertension, 3 had diabetes mellitus, 2 suffered from heart disease, 2 had infarctus myocardii, 1 had hyperlipidemia, 1 had atrial fibrillation. Additionally, those patients had neuroimaging (CT or MRI) evidence of vascular disease in one or more vascular territories. Patients with vascular parkinsonism were older, had shorter duration of disease, were more likely to present rigidity rather than tremor. Dementia and incontinence were more common in vascular group than in Parkinson's disease group. Patients with vascular parkinsonism were also significantly more likely to have corticospinal findings. Proving that Parkinson's disease had vascular etiology is extremely difficult. The test results are inconclusive.","Adult;Aged;Aged, 80 and over;Brain/*blood supply/pathology/radiography;Cerebrovascular Circulation/physiology;Dementia/diagnosis/epidemiology;Female;Humans;Hypertension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Parkinsonian Disorders/diagnosis/epidemiology/*physiopathology;Prevalence;Risk Factors;Tomography, X-Ray Computed;Urinary Incontinence/diagnosis/epidemiology","Honczarenko, K.;Budzianowska, A.",2003,,,0,
3822,Diagnosing dementia: do we get it right?,"To find out whether the diagnosis of dementia agreed with findings at necropsy a detailed assessment of 27 elderly patients (mean age 82 (range 70-94] presenting with dementia was conducted at a combined department of geriatric medicine and psychiatry for the elderly. On the basis of the results the cause of the dementia was diagnosed clinically. Neuropathological examinations were performed after death. The clinical diagnosis made during life was not supported by the findings at necropsy in 11 cases. Alzheimer's disease was overdiagnosed in life (13 cases, of which only six were confirmed at necropsy). Although the clinical investigation was limited by availability of resources, neither cranial computed tomography nor the Hachinski score helped to distinguish between multi-infarct dementia and Alzheimer's disease in this age group. This study confirms the value of neuropathological studies in the precise diagnosis of dementia.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;Brain/*pathology;Dementia/*diagnosis/pathology;Dementia, Multi-Infarct/diagnosis/pathology;Diagnosis, Differential;Female;Humans;Male","Homer, A. C.;Honavar, M.;Lantos, P. L.;Hastie, I. R.;Kellett, J. M.;Millard, P. H.",1988,Oct 8,,0,
3823,Diffusion magnetic resonance histograms as a surrogate marker and predictor of disease progression in CADASIL: a two-year follow-up study,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. MRI is sensitive in detecting preclinical involvement and changes over time. However, little is known about correlations between MRI metrics and clinical measures on a longitudinal scale. In this study, we assessed the role of quantitative MRI (T2-lesion volume and diffusion tensor imaging [DTI]-derived metrics) in monitoring and predicting disease progression. METHODS: Sixty-two CADASIL subjects were followed prospectively over a period of 26.3+/-1.2 months. Dual-echo scans, DTI scans, and clinical scales were obtained at baseline and at follow-up. T2-lesion volumes were determined quantitatively, and histograms of mean diffusivity (MD) were produced. RESULTS: At follow-up, T2-lesion volumes and MD histogram metrics had changed significantly (all P<0.01). Lesion volumes and average MD correlated with clinical scores at baseline. Changes of average MD correlated with changes of the Rankin score, the National Institutes of Health Stroke Scale score, and the structured interview for the diagnosis of Alzheimer dementia and multiinfarct dementia score (all P<0.01). On multivariate analysis, average MD and systolic blood pressure at baseline were predictors of changes of average MD during follow-up. Moreover, average MD was the main predictor of clinical progression. Sample size estimates showed that the number of individuals required to detect a treatment effect in an interventional trial may be reduced when using MD histograms as an end point. CONCLUSIONS: This study establishes correlations between changes of DTI histogram metrics and clinical measures over time. DTI histograms may be used as an adjunct outcome measure in future therapeutic trials. Moreover, DTI histogram metrics predict disease progression in CADASIL.",Adult;CADASIL/ diagnosis;Cross-Sectional Studies;Diffusion Magnetic Resonance Imaging;Disease Progression;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Multivariate Analysis;Predictive Value of Tests;Prognosis;Prospective Studies;Risk Factors;Sample Size;Sensitivity and Specificity,"Holtmannspotter, M.;Peters, N.;Opherk, C.;Martin, D.;Herzog, J.;Bruckmann, H.;Samann, P.;Gschwendtner, A.;Dichgans, M.",2005,Dec,10.1161/01.STR.0000189696.70989.a4,0,
3824,Brain perfusion SPECT using an annular single crystal camera: initial clinical experience,"The annular single-crystal brain camera (ASPECT) is a digital SPECT system with a single-crystal sodium iodide thallium Nal(Tl) ring detector and collimator system designed to view the patient's head from three angles simultaneously. The ring is rotated concentrically to the detector for three-dimensional reconstruction over a 21.4 cm (diameter) by 10.7 cm (length) field of view. We evaluated the system clinically by imaging a Hoffman brain phantom and seven subjects, of whom two were normal controls, three had previous cerebral infarction and two had dementia. The ASPECT system produced tomographic images of high spatial resolution. In normal subjects, the separation of striata from thalami by the posterior limbs of the internal capsules was much clearer on ASPECT images than on rotating gamma camera images. The high spatial resolution obtained with the ASPECT system translates into superior anatomical representation of the brain compared to the standard rotating gamma camera.","Adult;Aged;Brain/ radionuclide imaging;Cerebral Infarction/radionuclide imaging;Cerebrovascular Circulation;Dementia/radionuclide imaging;Equipment Design;Female;Gamma Cameras;Humans;Male;Middle Aged;Models, Structural;Organotechnetium Compounds;Oximes;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/ instrumentation","Holman, B. L.;Carvalho, P. A.;Zimmerman, R. E.;Johnson, K. A.;Tumeh, S. S.;Smith, A. P.;Genna, S.",1990,Sep,,0,
3825,Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes,"Small vessel disease is a stroke subtype characterized by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. Participants with small vessel disease (n = 118; mean age = 68.9 years; 65% male) defined as a clinical and magnetic resonance imaging confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. Healthy controls (n = 398; mean age = 64.3 years; 52% male) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify: (i) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment; and (ii) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole-brain voxel-based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = -0.23, P </= 0.001) and depression (r = -0.41, P </= 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = -0.38, P </= 0.001), but not depression (r = -0.16, P = 0.09). On voxel-based analysis, apathy was associated with widespread reduction in white matter integrity, with the strongest effects in limbic association tracts such as the anterior cingulum, fornix and uncinate fasciculus. In contrast, when controlling for apathy, we found no significant relationship between our white matter parameters and symptoms of depression. In conclusion, white matter microstructural changes in small vessel disease are associated with apathy but not directly with depressive symptoms. These results suggest that apathy, but not depression, in small vessel disease is related to damage to cortical-subcortical networks associated with emotion regulation, reward and goal-directed behaviour.",,"Hollocks, M. J.;Lawrence, A. J.;Brookes, R. L.;Barrick, T. R.;Morris, R. G.;Husain, M.;Markus, H. S.",2015,Dec,10.1093/brain/awv304,0,
3826,Clinical use of CT and MR scans in psychiatric patients,"During a three-year period, 337 CT or MR scans were ordered for psychiatric patients in a teaching hospital. Scans were normal in 185 instances, equivocal in 34, and abnormal in 118 instances. When a history of neurologic disorder and/or the presence of abnormal neurologic/organic mental signs was positive, scans were abnormal in 74% of cases; when these indicators were negative, scans were normal in 72% of cases. In all, only 4 new diagnoses were made. Two patients, both with markedly abnormal neurological findings, were shown to have brain tumors, which changed their management. Two others showed abnormalities which would have been missed, both of which were of no clinical consequence. The following are suggested as sound indications for ordering CT or MR brain imaging among psychiatric patients: 1) positive history of head injury, stroke or other neurologic disease, as well as suspected Alzheimer disease or multi-infarct dementia; 2) presence of abnormal neurologic signs or organic mental signs, such as confusion or cognitive decline; and, 3) a first psychotic break or personality change after the age of 50 years.",,"Hollister, L. E.;Boutros, N.",1991,Nov,,0,
3827,Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy,"Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = −0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with axonal disruption, where lower FA was associated with greater axonal disruption in white matter directly adjacent to hyperphosphorylated tau positive sulci. In summary, our findings indicate that axonal disruption and tau pathology are closely associated, and high spatial resolution ex vivo diffusion MRI has the potential to detect microstructural alterations observed in CTE tissue. Future studies will be required to determine whether this approach can be applied to living people.",aged;Alzheimer disease;article;axon;axonal injury;brain degeneration;brain histology;brain tissue;cerebrovascular disease;chronic traumatic encephalopathy;comorbidity;controlled study;diffuse Lewy body disease;diffusion tensor imaging;diffusion weighted imaging;ex vivo study;fractional anisotropy;frontal cortex;gray matter;hippocampal sclerosis;histopathology;human;human tissue;immunoreactivity;leukoencephalopathy;myelinated nerve;neurofibrillary tangle;nuclear magnetic resonance scanner;priority journal;protein phosphorylation;tauopathy;traumatic brain injury;very elderly;white matter,"Holleran, L.;Kim, J. H.;Gangolli, M.;Stein, T.;Alvarez, V.;McKee, A.;Brody, D. L.",2017,,10.1007/s00401-017-1686-x,0,
3828,Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease,"Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood-brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.","Animals;Atrophy/pathology;Blood-Brain Barrier/pathology;Brain/ pathology;Cerebral Small Vessel Diseases/complications/ pathology;Cognition;Diffusion Tensor Imaging;Disease Models, Animal;Magnetic Resonance Imaging;Male;Mice, Inbred C57BL;Microvessels/ pathology;Neuroglia/pathology;White Matter/pathology","Holland, P. R.;Searcy, J. L.;Salvadores, N.;Scullion, G.;Chen, G.;Lawson, G.;Scott, F.;Bastin, M. E.;Ihara, M.;Kalaria, R.;Wood, E. R.;Smith, C.;Wardlaw, J. M.;Horsburgh, K.",2015,Jun,10.1038/jcbfm.2015.12,0,
3829,"Spatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy aging","BACKGROUND AND PURPOSE: White-matter hyperintensities (WMHs) detected by magnetic resonance imaging are thought to represent the effects of cerebral small-vessel disease and neurodegenerative changes. We sought to determine whether the spatial distribution of WMHs discriminates between different disease groups and healthy aging individuals and whether these distributions are related to local cerebral perfusion patterns. METHODS: We examined the pattern of WMHs by T2/fluid-attenuated inversion recovery-weighted magnetic resonance imaging in 3 groups of subjects: cerebral amyloid angiopathy (n=32), Alzheimer disease or mild cognitive impairment (n=41), and healthy aging (n=29). WMH frequency maps were calculated for each group, and spatial distributions were compared by voxel-wise logistic regression. WMHs were also analyzed as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography atlas. RESULTS: Although WMH volume was greater in cerebral amyloid angiopathy and Alzheimer disease/mild cognitive impairment than in healthy aging, there was no consistent difference in the spatial distributions when controlling for total WMH volume. Hyperintensities were most frequent in the deep periventricular WM in all 3 groups. A strong inverse correlation between hyperintensity frequency and normal perfusion was demonstrated in all groups, demonstrating that WMHs were most common in regions of relatively lower normal cerebral perfusion. CONCLUSIONS: WMHs show a common distribution pattern and predilection for cerebral WM regions with lower atlas-derived perfusion, regardless of the underlying diagnosis. These data suggest that across diverse disease processes, WM injury may occur in a pattern that reflects underlying tissue properties, such as relative perfusion.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology/radionuclide imaging;Cerebral Amyloid Angiopathy/ pathology/radionuclide imaging;Cerebrovascular Circulation;Cognition Disorders/pathology/radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology/radionuclide imaging;Tomography, Emission-Computed, Single-Photon","Holland, C. M.;Smith, E. E.;Csapo, I.;Gurol, M. E.;Brylka, D. A.;Killiany, R. J.;Blacker, D.;Albert, M. S.;Guttmann, C. R.;Greenberg, S. M.",2008,Apr,10.1161/strokeaha.107.497438,0,
3830,[Cerebral CT findings in AIDS] Cerebrale CT-funn ved AIDS,"A cerebral CT was performed in 82 of 525 AIDS patients, with positive findings in 46 cases. These findings included cerebral atrophy in 28 cases, pathological demyelinisation in two, progressive multifocal leukoencephalopathy in one, toxoplasmosis in 11, lymphomas in seven, infarction in one and one subdural haematoma. The radiological findings are correlated to pathology and clinical symptoms. The authors point out the importance of these findings for correct interpretation of the CT scans.","AIDS Dementia Complex/diagnostic imaging/pathology;AIDS-Related Opportunistic Infections/diagnostic imaging/pathology;Acquired Immunodeficiency Syndrome/ diagnostic imaging/pathology;Adult;Aged;Atrophy;Brain/ diagnostic imaging;Brain Diseases/ diagnostic imaging/pathology;Demyelinating Diseases/diagnostic imaging/pathology;Encephalitis, Viral/diagnostic imaging/pathology;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Hol, P. K.;Dunlop, O.",1997,Sep 10,,0,
3831,[Cerebral CT findings in AIDS],"A cerebral CT was performed in 82 of 525 AIDS patients, with positive findings in 46 cases. These findings included cerebral atrophy in 28 cases, pathological demyelinisation in two, progressive multifocal leukoencephalopathy in one, toxoplasmosis in 11, lymphomas in seven, infarction in one and one subdural haematoma. The radiological findings are correlated to pathology and clinical symptoms. The authors point out the importance of these findings for correct interpretation of the CT scans.","AIDS Dementia Complex/pathology/radiography;AIDS-Related Opportunistic Infections/pathology/radiography;Acquired Immunodeficiency Syndrome/pathology/*radiography;Adult;Aged;Atrophy;Brain/*radiography;Brain Diseases/pathology/*radiography;Demyelinating Diseases/pathology/radiography;Encephalitis, Viral/pathology/radiography;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Hol, P. K.;Dunlop, O.",1997,Sep 10,,0,
3832,Subcortical type cognitive impairment in herpes zoster encephalitis,"Nine immunocompetent patients with acute herpes tester encephalitis (HZE) were studied with the help of neurological, neuroradiological and neuropsychological investigations. All patients were treated with acyclovir. Neuropsychological performance was compared with that of a group of 16 healthy controls. Computed tomography of the head showed infarct-like hypodense lesions in two patients, involving the internal capsule in one case and the temporoparietal cortex and white matter in another. Hypoperfusion shown by single photon emission computed tomography, mostly involving the frontal areas bilaterally, was seen in six of the seven patients examined. Hyperperfusion as seen in herpes simplex encephalitis was not encountered. One patient remained mildly demented, but all the other patients recovered relatively well. Neuropsychological examination after acyclovir treatment showed a decline in memory and speed of cognitive processes, without circumscribed neuropsychological deficits. Six of the nine patients showed behavioural disinhibition, and mood changes were also observed. Memory impairment in HZE was not as global or as severe as is described after encephalitis due to herpes simplex virus. In HZE both the brain perfusion pattern and the neuropsychological test profile showed features compatible with subcortical dysfunction.",aciclovir;antivirus agent;adolescent;adult;aged;article;behavior disorder;brain infarction;brain perfusion;brain tomography;capsula interna;clinical article;cognitive defect;computer assisted tomography;dementia;frontal lobe;herpes zoster;human;mood;neurologic examination;neuropsychological test;neuroradiology;parietal lobe;priority journal;single photon emission computer tomography;temporal cortex;virus encephalitis;white matter,"Hokkanen, L.;Launes, J.;Poutiainen, E.;Valanne, L.;Salonen, O.;Sirén, J.;Iivanainen, M.",1997,,,0,
3833,"Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease","Context: The pathogenesis of leukoaraiosis on computed tomographic (CT) scanning is unknown, but cerebrovascular risk factors for leukoaraiosis show overlap with those for Alzheimer disease (AD). Objective: To investigate the contribution of cerebro-vascular risk factors, in particular plasma total homocysteine (tHcy), to leukoaraiosis in patients with AD and controls. Design: Cross-sectional case-control study. Setting: Referral population to a hospital clinic and community volunteers from the Oxfordshire region in England seen between July 1, 1988, and July 1, 2000. Participants: One hundred thirty-seven AD cases (104 confirmed post mortem) and 277 controls matched for age (mean±SD, 73±8 years) and sex. Main Outcome Measures: Cerebrovascular risk factors and leukoaraiosis on CT scans of cases and controls; the odds ratio (OR) of having moderate to severe leukoaraiosis with higher levels of plasma tHcy and cerebrovascular risk factors such as age, sex, systolic blood pressure, smoking, diabetes mellitus, and apolipoprotein E ε4 genotype. Results: Leukoaraiosis was more prevalent in AD cases. For a 5-μmol/L increase in tHcy levels, the OR for leukoaraiosis was 1.40 (95% confidence interval, 1.02-1.91) independent of other risk factors. The distribution pattern of leukoaraiosis was more marked in the deep white matter than in the periventricular area in individuals with elevated tHcy levels, particularly in patients with AD. Conclusions: Higher tHcy levels are an independent risk factor for moderate to severe leukoaraiosis in individuals with AD and of leukoaraiosis of the deep white matter in particular. The nature of the relationship between tHcy levels and leukoaraiosis in AD requires further longitudinal and intervention studies.",apolipoprotein E4;homocysteine;aged;allelism;Alzheimer disease;article;cerebrovascular disease;smoking;computer assisted tomography;controlled study;diabetes mellitus;genotype;human;leukoaraiosis;major clinical study;priority journal;protein blood level;risk assessment;risk factor;systolic blood pressure;United Kingdom;white matter,"Hogervorst, E.;Ribeiro, H. M.;Molyneux, A.;Budge, M.;David Smith, A.",2002,,,0,
3834,The corpus callosum in communicating and noncommunicating hydrocephalus,"To investigate morphological changes in the corpus callosum in hydrocephalus and to correlate them with clinical findings we studied sagittal T2*-weighted cine MR images of 163 patients with hydrocephalus. The height, length and cross-sectional area of the corpus callosum were measured and related to the type of cerebrospinal fluid flow anomaly and to clinical features, especially dementia. With expansion of the lateral ventricles the corpus callosum showed mainly elevation of its body and, to a lesser degree, increase in length. Upward bowing was more pronounced in noncommunicating than in communicating hydrocephalus. Dorsal impingement on the corpus callosum by the free edge of the falx correlated with the height of the corpus callosum. Cross-sectional area did not correlate with either height, length or impingement; it was, however, the strongest anatomical discriminator between demented and nondemented patients. The area of the corpus callosum was significantly smaller in patients with white matter disease. Our findings suggest that, due to its plasticity, the corpus callosum can to some degree resist distortion in hydrocephalus. Dementia, although statistically related to atrophy of the corpus callosum, is possibly more directly related to white matter disease.",Case-Control Studies;Corpus Callosum/anatomy & histology/ pathology;Dementia/etiology/pathology;Female;Humans;Hydrocephalus/complications/ pathology;Magnetic Resonance Imaging;Male;Middle Aged,"Hofmann, E.;Becker, T.;Jackel, M.;Metzner, D.;Schneider, M.;Meixensberger, J.;Reichmann, H.",1995,Apr,,0,
3835,The spectrum of aphasia subtypes and etiology in subacute stroke,"Background: Aphasia is one of the most common stroke syndrome presentations, yet little is known about the spectrum of different subtypes or their stroke mechanisms. Yet, subtypes and etiology are known to influence the prognosis and recovery. Aim: Our aim is to analyze aphasia subtypes and etiology in a large subacute stroke population. Methods: Consecutive patients from a dedicated cognitive stroke registry were accrued. A validated cognitive screening examination was administered during the first month of stroke presentation, which enabled a diagnosis of 14 different aphasic subtypes. The evolution from one subtype to another in the acute and subacute period, at times, resulted in more than 1 subtype being diagnosed. Etiology of stroke was determined by the modified Trial of Org 10172 in Acute Stroke Treatment criteria that included intracerebral hemorrhage. Exclusions included dementia, chronic medical illness, substance abuse, and severe depression. Results: Of 2389 stroke patients, after exclusions (n = 593), aphasias numbered 625 (625 of 1796; 34.8%), and the subtype frequencies included Broca aphasia (n = 170; 27.2%), anomic aphasia (n = 165; 26.4%), global aphasia (n = 119; 19.04%), and subcortical aphasia (n = 57; 9.12%). Less frequent subtypes (total n = 40; 6.7%) included transcortical aphasia (n = 11), Wernicke aphasia (n = 10), conduction aphasia (n = 7), aphemia (n = 3), semantic aphasia (n = 3), crossed aphasia (n = 3), pure word deafness (n = 2), and foreign accent syndrome (n = 1). Aphasia subtypes and etiologies had some significant associations (chi-square: 855.8, P value <.0001). Bonferroni-adjusted P values revealed that anomic aphasia had a significant association with small-vessel disease (SVD) (odds ratio [OR] = 2.0254, 95% confidence interval [CI]: 1.3820-2.9681), and global aphasia patients mostly had cardioembolic (CE) causes (OR = 2.3589, 95% CI: 1.5506-3.5885) and less likely SVD (OR =.2583, 95% CI:.1444-.4654). Other notable inferences were included. Wernicke aphasia was caused by either CE (6 of 12; 50%) or hemorrhage (4 of 12; 33.3%) in a combined 83% of cases. Subcortical aphasia was because of SVD in 36% (31 of 85) or because of hemorrhage in 32% (27 of 85) yielding a combined 68% of cases. Sixty percent of transcortical aphasias as a group were because of either large-vessel disease (7 of 20; 35%) or hemorrhage (5 of 20; 25%). Alternatively, a diagnosis of Broca aphasia could be because of any of the etiological categories. Conclusions: (1) Aphasias are a heterogeneous entity in subtype and etiology; (2) Broca, global, anomic, and subcortical aphasias accounted for the vast majority of aphasia subtypes; (3) SVD, cardioembolism, and hemorrhage are significantly associated with certain signature aphasic syndromes; and (4) determination of aphasia subtype can assist with etiology, prognosis, influence aphasia therapy, and provide the basis for future randomized controlled trials with pharmacological therapy or behavioral therapy. © 2013 Elsevier B.V. All rights reserved.",acute disease;adult;aged;anomic aphasia;aphasia;aphemia;article;ataxic aphasia;brain hemorrhage;cardioembolic stroke;cerebrovascular accident;conduction aphasia;cortical sensory aphasia;cross aphasia;foreign accent syndrome;global aphasia;human;large vessel disease;major clinical study;morbidity;nuclear magnetic resonance imaging;priority journal;pure word deafness;semantic aphasia;small vessel vasculitis;subacute stroke;subcortical aphasia;transcortical aphasia;vasculitis,"Hoffmann, M.;Chen, R.",2013,,,0,
3836,The panoply of field-dependent behavior in 1436 stroke patients. The mirror neuron system uncoupled and the consequences of loss of personal autonomy,"Evaluation of the multifaceted nature of frontal network syndromes is uniquely challenging and rarely tested in the acute/sub-acute stroke period. Field-dependent behavior such as imitation behavior, utilization behavior, and environmental dependency syndrome, as a component of altered environmental autonomy, may be a reliable bedside test. This research focused on the frequency of field-dependent behavior in stroke, the subtypes and relation to frontal lobe lesion location and stroke etiology. A validated frontal network score incorporating a 10-point imitation behavior scale was applied to alert patients without significant aphasia, encephalopathy, dementia, or substance abuse. Discriminative validity assessment with magnetic resonance imaging, diffusion weight imaging (MRI-DWI brain) was performed and correlational validity was established using standard neuropsychological tests. Of the stroke patients (n = 1436), those with frontal network symptoms (335/1203; 28%) were analyzed further. In the 73 patients with lesions restricted to the frontal lobes or the frontal subcortical circuits, 56 complied with the 10-point imitation behavior scale testing. Forty-five of 56 (80%) demonstrated imitation behavior (sensitivity 73% and specificity 94%). Correlational validity testing with four commonly used frontal lobe neuropsychological tests was good. The stroke etiology included 26 (59%) ""other"" causes, 9 (20%) intracerebral hemorrhages, 3 (7%) cardioembolic causes, 3 (7%) large vessel disease, 2 (4%) small vessel disease, and 2 (4%) unknown etiology. Field-dependent behaviour subtypes included imitation behavior (n = 45), utilization behavior (n = 9), environmental dependency syndrome (n = 4), and complex other forms of environmental dependence syndrome (n = 5). It was concluded that imitation behavior is a relatively common occurrence with lesions in the frontal lobes in the acute/sub-acute stroke period and is associated predominantly with non-mainstream (other) stroke causes and intracerebral hemorrhage. © 2013 © 2013 Taylor & Francis.",,"Hoffmann, M.",2014,September,,0,
3837,Intravascular large B‑cell lymphoma: A rare and potentially reversible cause of cerebral stroke,"Intravascular lymphoma (IVL), a rare, extranodal form of non-Hodgkin lymphoma (NHL), can cause infarcts by occluding small arteries of the brain. Owing to its heterogeneous clinical manifestations and unfavorable prognosis, the diagnosis is often made postmortem. Patients can present with a range of motor or sensory deficits, rapid cognitive impairment, aphasia or signs of myelitis, often with nonspecific radiographic findings.Timely recognition of a treatable disease is essential to prevent permanent neurocognitive defects. We present a case who could be treated successfully with chemotherapy.",carmustine;CD20 antigen;cyclophosphamide;doxorubicin;lactate dehydrogenase;methotrexate;prednisolone;rituximab;thiotepa;vincristine;adult;aphasia;article;autologous stem cell transplantation;brain biopsy;brain ischemia;brain vasculitis;cancer chemotherapy;case report;cerebrospinal fluid examination;consciousness;contrast enhancement;differential diagnosis;drug megadose;dyslipidemia;focal epilepsy;gait disorder;hearing impairment;human;human tissue;lactate dehydrogenase blood level;large cell lymphoma;male;MELAS syndrome;middle aged;multiple cycle treatment;nuclear magnetic resonance imaging;priority journal;protein cerebrospinal fluid level;tinnitus;visual disorder,"Hofer, S.;Kessler, M.;Godau, J.;Weiler, D.;Frontzek, K.;Rushing, E. J.;Aebi, S.",2016,,,0,
3838,Parvalbumin-immunoreactive neurons in the normal human hippocampus,"Antibodies against parvalbumin, a cytoplasmic calcium-binding protein, were used for the immunocytochemical localization in the postmortem normal human hippocampus. Parvalbumin-containing neurons represent a subset of gamma-aminobutyric acid (GABA) neurons. Quantitative data were obtained by using a computer-assisted microscopic image-analyzing system. Parvalbumin immunoreactivity was demonstrated in somata, dendrites and axons of nonpyramidal neurons in all subregions of the hippocampus proper and in the entorhinal cortex. The surface of parvalbumin-immunoreactive (parv-i) neurons was smooth or sparsely spinous. In the hippocampus proper complete staining of dendritic processes and somata of parv-i neurons enabled their classification. In the dentate gyrus parv-i neurons were localized in or below the granular layer as well as in the center of the hilus. Nonreactive granule cell somata were surrounded by a dense plexus of parv-i axonal varicosities. In Ammon's horn parv-i somata were localized predominantly in the stratum (s.) pyramidale and s. oriens. Most parv-i neurons were localized in CA1, sending long dendrites into the s. radiatum. Parv-i axons and axonal varicosities were found almost exclusively around nonreactive neuronal somata in the s. pyramidale. In the subiculum parv-i neurons were scattered in all layers. In the entorhinal cortex the number of parv-i neurons was much higher compared to the hippocampus proper, but their dendrites often show faint or incomplete staining. Parv-i somata and axon varicosities were found in the islands of layer II, but with the greatest number in layer III. These findings will form the basis for comparisons with the parv-i neuronal populations of patients with senile dementia of the Alzheimer type, multi-infarct dementia and Parkinson's disease.",,"Hochli, M.;Zetsche, T.;Chan-Palay, V.",1991,1991,,0,
3839,Automated quantification of caudate atrophy by local registration of serial MRI: evaluation and application in Huntington's disease,"OBJECTIVE: Caudate atrophy rate measured from serial MRI is proposed as a biomarker of HD progression that may be of use in assessing putative disease-modifying agents. Manual measurement techniques are the most widely applied but are time-consuming. We describe and evaluate an automated technique based on a local registration and boundary shift integral (BSI) approach at the caudate-CSF and caudate-white matter boundaries; caudate boundary shift integral (CBSI). METHODS: Two-year caudate volume change was measured in controls, premanifest HD and early HD using the CBSI and compared with a detailed manual measure in terms of 1) raw caudate volume change, 2) group differentiation, 3) associations with clinical variables and 4) rater requirements. CBSI additivity was assessed by comparing measurements over a single scan pair (baseline-->2 years), with the sum of measurements from two scan pairs (baseline-->1 year-->2 years). RESULTS: Techniques produced comparable caudate volume change measurements, although CBSI under-reported by 0.04 ml relative to manual. Both techniques distinguished controls, premanifest and early HD with a stepwise increase in rates across groups. Higher rates (CBSI and manual) were associated with increased proximity to estimated disease onset but not clinical change scores. CBSI reduced rater requirements by 2/3 (2 h per subject) relative to manual for this three time-point investigation. CBSI measurements over one scan pair showed good agreement with the sum of measurements from two scan pairs. CONCLUSIONS: CBSI results were comparable to a manual measure but with reduced rater requirements. CBSI may be of use in large-scale studies of HD.","Adult;Algorithms;Artificial Intelligence;Atrophy/pathology;Brain/*pathology;Caudate Nucleus/*pathology;Humans;Huntington Disease/*pathology;Image Enhancement/methods;Image Interpretation, Computer-Assisted/*methods;Magnetic Resonance Imaging/*methods;Middle Aged;Pattern Recognition, Automated/*methods;Reproducibility of Results;Sensitivity and Specificity;*Subtraction Technique","Hobbs, N. Z.;Henley, S. M.;Wild, E. J.;Leung, K. K.;Frost, C.;Barker, R. A.;Scahill, R. I.;Barnes, J.;Tabrizi, S. J.;Fox, N. C.",2009,Oct 1,10.1016/j.neuroimage.2009.06.003,0,
3840,The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study,"BACKGROUND: Unbiased longitudinal studies are needed to understand the distributed neurodegenerative changes of Huntington's disease (HD). They may also provide tools for assessing disease-modifying interventions. The authors investigated the progression of regional atrophy in premanifest and early HD compared with controls. METHODS: Nine controls, 17 premanifest and 21 early HD subjects underwent volumetric MRI at baseline and 2 years. Premanifest subjects were on average 18.1 years before predicted motor onset. Non-linear registration was used to model within-subject change over the scanning interval, and statistical parametric mapping was used to examine group differences and associations with clinical variables. RESULTS: In early HD, increased grey-matter (GM) atrophy rates were evident throughout the subcortical GM and over selective cortical regions compared with controls. This group also demonstrated strikingly widespread increases in white-matter (WM) atrophy rates. The authors observed no significant differences between premanifest HD and controls. Longer CAG was associated with higher atrophy rates over large WM areas including brainstem and internal capsule and over small GM regions including thalamus and occipital cortex. Worse baseline motor score was associated with regionally increased rates in the thalamus, internal capsule and occipital lobe. Sample-size calculations indicate that 19 and 24 early HD subjects per treatment arm would need to complete a 2-year trial in order to detect a 50% reduction in WM and GM atrophy rates respectively. CONCLUSIONS: Degeneration of structural connectivity may play an important role in early HD symptoms. Assessment of WM and GM changes will be important in understanding the complexity of HD and its treatment.","Adult;Atrophy;Brain/*pathology;Cohort Studies;Disease Progression;Female;Humans;Huntington Disease/genetics/*pathology;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Models, Statistical;Movement/physiology;Regression Analysis;Repetitive Sequences, Nucleic Acid;Sample Size","Hobbs, N. Z.;Henley, S. M.;Ridgway, G. R.;Wild, E. J.;Barker, R. A.;Scahill, R. I.;Barnes, J.;Fox, N. C.;Tabrizi, S. J.",2010,Jul,10.1136/jnnp.2009.190702,0,
3841,"Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study","Background: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. Methods 40 controls and 61 early",,"Hobbs, N. Z.;Cole, J. H.;Farmer, R. E.;Rees, E. M.;Crawford, H. E.;Malone, I. B.;Roos, R. A. C.;Sprengelmeyer, R.;Durr, A.;Landwehrmeyer, B.;Scahill, R. I.;Tabrizi, S. J.;Frost, C.",2013,2013,,0,
3842,Relationship between apolipoprotein E4 genotype and white matter integrity in HIV-positive young adults in South Africa,"HIV-associated dementia (HAD) is a serious neuropsychiatric disorder affecting people with AIDS. Host genotype may affect the pathogenesis of HIV in the central nervous system (CNS). One gene relevant to the individual variation in acquiring HAD may be Apolipoprotein E (ApoE). We aimed to investigate the relationship of ApoE genotype to neuropsychological function and white matter integrity of the corpus callosum in a region of interest a priori analysis of HIV-positive subjects with clade C HIV. Forty-five subjects underwent ApoE genotyping, neuropsychological testing, and diffusion tensor imaging (DTI). Subjects (n = 24) with at least one epsilon4 allele when compared to subjects with no epsilon4 allele (n = 19) had significantly decreased immediate and delayed recall on the Hopkins Verbal Learning test (p = 0.05) and significantly decreased fractional anisotrophy in the corpus callosum (p = 0.007). These data indicate that the epsilon4 allelic variant of ApoE is associated with memory impairment and white matter damage of the corpus callosum in HIV-positive subjects.","AIDS Dementia Complex/ genetics/ pathology/virology;Adolescent;Adult;Antigens, CD4/metabolism;Apolipoproteins E/ genetics;Corpus Callosum/ pathology/virology;Diffusion Tensor Imaging;Female;Gene Frequency;Genotype;Humans;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Psychiatric Status Rating Scales;South Africa/epidemiology;Statistics, Nonparametric;Young Adult","Hoare, J.;Westgarth-Taylor, J.;Fouche, J. P.;Combrinck, M.;Spottiswoode, B.;Stein, D. J.;Joska, J. A.",2013,Apr,10.1007/s00406-012-0341-8,0,
3843,A diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals,"HIV-associated prospective memory (ProM) impairment has emerged, in earlier studies as a significant predictor of medication management and independence in activities of daily living. The relationship between ProM and white matter integrity in HIV has not previously been investigated. Participants, including 128 HIV-infected individuals and 32 healthy controls, were assessed using a comprehensive neuropsychological evaluation and both objective and subjective measures of ProM. Diffusion tensor imaging (DTI) was utilized to investigate the relationship of white matter integrity to ProM in a randomly selected subsample of 40 HIV positive subjects, using a whole brain voxel-based approach to define fractional anisotrophy (FA) and mean diffusion (MD). Total prospective memory was significantly poorer in the HIV positive group when compared with healthy controls (p = 0.023). Time-based ProM was poorer in the HIV group compared to healthy controls both without prompts (p = 0.001) and with prompts (p = 0.001). Poor Total ProM score correlated with performance on neuropsychological tests of executive functioning, information processing speed, learning, and working memory (p < 0.05). Those HIV positive participants with poor ProM had significantly decreased FA in the regions of superior corona radiata (p = 0.0035), the corpus collosum (p = 0.006) and the cingulum (p = 0.0033) when compared to those who were HIV positive with good ProM. This study reinforces the importance of ProM assessment in HIV.","AIDS Dementia Complex [pathology] [physiopathology] [psychology];Adolescent;Case-Control Studies;Diffusion Tensor Imaging [methods];HIV Seropositivity [pathology] [physiopathology] [psychology];Memory Disorders [pathology] [physiopathology] [virology];Nerve Fibers, Myelinated [metabolism] [pathology];South Africa;Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Young Adult[checkword]","Hoare, J.;Jacqueline, H.;Westgarth-Taylor, J.;Jenny, W. T.;Fouche, J. P.;Jean-Paul, F.;Spottiswoode, B.;Bruce, S.;Paul, R.;Robert, P.;Thomas, K.;Kevin, T.;Stein, D.;Dan, S.;Joska, J.;John, J.",2012,,10.1007/s11011-012-9311-0,0,
3844,White matter micro-structural changes in ART-naive and ART-treated children and adolescents infected with HIV in South Africa,"OBJECTIVE: To describe the effect of HIV on white matter integrity and neurocognitive function in children vertically infected with HIV, compared to a HIV-negative healthy control group. DESIGN: Cross-sectional. METHODS: We compared 75 HIV-infected children aged 6-16 years, including children on antiretroviral therapy (ART) and those who were ART-naive, with 30 controls on diffusion tensor imaging and a neuropsychological battery sensitive to fronto-striatal pathology. In a secondary analysis, we compared 'slow progressor' ART-naive children, children on ART without a diagnosis of encephalopathy and children on ART with HIV encephalopathy. RESULTS: Compared to controls (n = 30), HIV-infected children (n = 75) displayed decreased fractional anisotropy and axial diffusion, and increased mean diffusivity and radial diffusion, indicating damaged neuronal microstructure. HIV-infected children performed poorly on the neuropsychological battery (P = <0.001). Within the HIV-infected group, children with HIV encephalopathy (n = 14) had poor white matter integrity when compared to ART-treated children without encephalopathy (n = 41), and there was significant myelin loss in ART-naive children (n = 20), compared with ART-treated children. ART-treated children had significant axonal damage in the corpus callosum (P = 0.009). CONCLUSION: Children infected with HIV, irrespective of treatment status, displayed significantly poorer white matter integrity and impaired cognition compared to HIV-negative controls. Our findings suggest that despite immune recovery in children on ART, they remain at risk for developing central nervous system disease, and that initiation of ART as early as possible may reduce the risk of developing white matter damage in ART-naive slow progressors.",AIDS Dementia Complex/*pathology;Adolescent;Anti-Retroviral Agents/*therapeutic use;Child;Cross-Sectional Studies;Diffusion Tensor Imaging;Female;HIV Infections/*drug therapy;Humans;Male;Neuropsychological Tests;South Africa;Treatment Outcome;White Matter/*pathology,"Hoare, J.;Fouche, J. P.;Phillips, N.;Joska, J. A.;Paul, R.;Donald, K. A.;Thomas, K. G.;Stein, D. J.",2015,Sep 10,10.1097/qad.0000000000000766,0,
3845,The imaging of HIV-related brain disease,"Advanced HIV disease is strongly associated with an increased occurrence of various neuropsychiatric disorders, and highly active antiretroviral therapy (HAART) is an important aspect of managing these conditions effectively. In addition, there is growing recognition that many HIV-infected individuals will develop neuropsychiatric disorders relatively early in the course of HIV disease, in many cases before CD4 cell counts drop below 500 cells/μl. However, it is not known who in the earlier phases of the disease will go on to develop neurocognitive disorders, or who will respond to treatment. New approaches in neuro-imaging have the potential to detect early HIV-associated damage in the brain. Preliminary evidence suggests that the neurotoxic effects of HIV result in damage to white matter tracts in the brain. Once damage is established and related cognitive disorders ensue, the ability of HAART to reverse existing dysfunction is probably limited. Earlier treatment with HAART in at-risk or minimally symptomatic patients may prevent further decline in cognition and delay the course of HIV disease.",,"Hoare, J.",2009,2009,,0,
3846,Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases,"OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.","Adenosine Triphosphate/analysis;Adult;Aged;Aged, 80 and over;Basal Ganglia/cytology/metabolism;Creatinine/analysis;Energy Metabolism/physiology;Humans;Huntington Disease/*diagnosis;Hydrogen-Ion Concentration;Magnetic Resonance Spectroscopy/*methods;Middle Aged;Nerve Fibers/chemistry/metabolism;Neurons/chemistry/metabolism/ultrastructure;Parkinson Disease/*diagnosis;Phosphorus Isotopes;Protons","Hoang, T. Q.;Bluml, S.;Dubowitz, D. J.;Moats, R.;Kopyov, O.;Jacques, D.;Ross, B. D.",1998,Apr,,0,
3847,Memory is preserved in older adults taking AT1 receptor blockers,"Background: Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. Methods: The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives. In post hoc analyses, we also examined (1) users of ARBs and angiotensin-converting enzyme inhibitors (ACEIs), (2) users of blood-brain barrier (BBB)-crossing ARBs and users of non-BBB-crossing ARBs, and (3) users of BBB-crossing ARBs and ACEIs (BBB crossers) and users of non-BBB-crossing ARBs and ACEIs (BBB noncrossers). Groups were compared regarding cognition and magnetic resonance imaging measures of brain volume and white matter hyperintensities (WMH), using analysis of covariance and multilevel models. Results: At baseline, the HTN-Other group performed worse than normotensives on Rey Auditory Verbal Learning Test (RAVLT) Immediate Recall (p = 0.002), Delayed Recall (p &lt; 0.001), Recognition Memory (p = 0.001), and Trails A (p &lt; 0.001) and B (p = 0.01). ARB users performed better than the HTN-Other group on Recognition Memory (p = 0.04) and worse than normotensives on Trails A (p = 0.04). The HTN-Other group performed worse than normotensives on Logical Memory Immediate (p = 0.02) and Delayed Recall over the 3-year follow-up (p = 0.007). Over the follow-up period, those taking BBB-crossing ARBs performed better than the HTN-Other group on AVLT Delayed Recall (p = 0.04), Logical Memory Immediate (p = 0.02), and Delayed Recall (p = 0.05). They also had fewer WMH than the HTN-Other group (p = 0.008) and those taking non-BBB-crossing ARBs (p = 0.05). There were no group differences in brain volume. Users of BBB-crossing medications (ARBs or ACEIs) showed better performance on AVLT Delayed Recall over time than all other groups, including normotensives (all p &lt; 0.01), and had less WMH volume over time than the BBB noncrossers group (p = 0.03), although they had more WMH volume than normotensives (p = 0.01). The BBB noncrossers group performed worse than normotensives on Logical Memory Delayed Recall over time (p = 0.01), but the BBB crossers group was not significantly different (p = 0.13). Conclusions: Hypertensive participants demonstrated worse baseline memory and executive function, as well as greater memory decline, over the 3-year follow-up than normotensives, unless they were ARB users, who showed preserved memory compared with those taking other antihypertensive drugs. Users of BBB-crossing ARBs showed superior memory performance over time compared with other antihypertensive drug users and had less WMH volume. Users of BBB-crossing medications (ARBs or ACEIs) showed better list-learning memory performance over time than all other groups, including normotensives, and had less WMH volume over time than users of non-BBB-crossing medications. These findings demonstrate that ARBs, especially those of the BBB-crossing variety, are associated with greater memory preservation and less WMH volume than other antihypertensive medications. &copy; 2017 The Author(s).",angiotensin receptor antagonist;candesartan;eprosartan;irbesartan;losartan;olmesartan;telmisartan;valsartan;adult;aged;Alzheimer disease;article;blood brain barrier;brain size;cognition;controlled study;executive function;female;follow up;human;hypertension;major clinical study;male;memory;neuroprotection;nuclear magnetic resonance imaging;post hoc analysis;Rey auditory verbal learning test;white matter,"Ho, J. K.;Nation, D. A.",2017,,10.1186/s13195-017-0255-9,0,
3848,CADASIL presenting as schizophreniform organic psychosis,"Objective: To describe an Asian patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting with schizophreniform organic psychosis. Methods: Case report. Results: We report a case of CADASIL in an Asian female presenting with frank psychotic symptoms. After resolution of her psychosis, she showed persistent distractibility, which indicated signs of cognitive impairment. Conclusion: Although neuropsychiatric symptoms are commonly present in this disorder, psychotic symptoms are rare and should be recognized. There is a need for timely diagnosis and management of this disorder.",flupentixol;risperidone;valproic acid;adult;article;auditory hallucination;basal ganglion;behavior change;CADASIL;case report;Chinese;cognitive defect;crying;disorientation;distractibility;electron microscopy;family history;female;grandiose delusion;histopathology;hospital admission;hospital discharge;hospital readmission;human;human tissue;lacunar stroke;laughter;middle aged;mood disorder;nuclear magnetic resonance imaging;pons;relapse;schizophreniform disorder;skin biopsy;visual hallucination;white matter,"Ho, C. S. H.;Mondry, A.",2015,,,0,
3849,Cerebral White Matter Changes on Therapeutic Response to Rivastigmine in Alzheimer's Disease,"BACKGROUND: Rivastigmine has been approved in the treatment of Alzheimer's disease (AD) patients as it can inhibit acetyl- and butyryl-cholinesterase and provide neuroprotective effects involving the synapses. White matter changes (WMCs) are frequently observed in AD, and clinical-pathological correlations imply their possible impacts on cognitive function by interference with cortical and subcortical neuronal pathways. OBJECTIVE: To evaluate the therapeutic effects of rivastigmine in AD patients with cerebral WMCs. METHODS: Clinically diagnosed AD patients from Kaohsiung Municipal Ta-Tung hospital were recruited together with their cranial magnetic resonance imaging and a series of annual psychometric tests, including Mini-Mental State Examination (MMSE) and sum of boxes of clinical dementia rating scale (CDR-SB). WMCs were rated through the modified Fazekas scale for the periventricular and deep WMCs. RESULTS: In total, 87 AD patients treated with rivastigmine were enrolled. Patients at severe stage of WMCs, compared to mild stage ones, had significant improvement evaluated by MMSE (periventricular WMCs, p = 0.025; deep WMCs, p = 0.030), but not CDR-SB. Compared to the worsening group, the clinically improving group had a significant higher ratio of pre-existing hypertension in terms of cognitive performance [p = 0.016, odds ratio (OR) = 3.48, 95% CI = 1.25-10.34], while having younger age (p = 0.043, OR = 0.11, 95% CI = 0.01-1.12) in terms of global status. CONCLUSION: Rivastigmine may provide better benefits in cognitive function, but not global status, for AD patients with more advanced WMCs. The detailed mechanisms still have to be determined in future studies.",Alzheimer's disease;cholinesterase inhibitors;rivastigmine;white matter changes,"Ho, B. L.;Kao, Y. H.;Chou, M. C.;Yang, Y. H.",2016,Aug 10,10.3233/jad-160364,0,
3850,A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly,"A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 8% in the frontal lobes and 12% in the occipital lobes-these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.","Aged;*Alleles;Brain/*anatomy & histology/metabolism;Genetic Predisposition to Disease;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Obesity/*genetics;Organ Size;Proteins/*genetics;Risk Factors","Ho, A. J.;Stein, J. L.;Hua, X.;Lee, S.;Hibar, D. P.;Leow, A. D.;Dinov, I. D.;Toga, A. W.;Saykin, A. J.;Shen, L.;Foroud, T.;Pankratz, N.;Huentelman, M. J.;Craig, D. W.;Gerber, J. D.;Allen, A. N.;Corneveaux, J. J.;Stephan, D. A.;DeCarli, C. S.;DeChairo, B. M.;Potkin, S. G.;Jack, C. R., Jr.;Weiner, M. W.;Raji, C. A.;Lopez, O. L.;Becker, J. T.;Carmichael, O. T.;Thompson, P. M.",2010,May 4,10.1073/pnas.0910878107,0,
3851,The Uncinate Fasciculus as a Predictor of Conversion from Amnestic Mild Cognitive Impairment to Alzheimer Disease,"BACKGROUND AND PURPOSE: Amnestic mild cognitive impairment (aMCI) is associated with the risk of Alzheimer's disease (AD). Although diffusion tensor imaging (DTI)-based fractional anisotropy (FA) analyses have been used to evaluate white matter changes in patients with AD, it remains unknown how FA values change during the conversion of aMCI to AD. This study aimed to elucidate the prediction of conversion to AD and cognitive decline by FA values in uncinate fasciculus (UF) in aMCI patients. METHODS: Twenty-two aMCI patients were evaluated for their UF FA values by a tractography-based method with DTI and cognitive performance by neuropsychological testing at baseline and after a 3-year follow-up. Patients were divided into 2 groups after 3 years: 14 aMCI-stable (aMCI-aMCI) and 8 AD-conversion (aMCI-AD). RESULTS: At baseline, FA values in the right UF were significantly lower in the aMCI-AD group than in the aMCI-aMCI group. These values also showed significant correlations with the neuropsychological scores after a 3-year follow-up. The area under the curve of the receiver operation characteristic curves for predicting conversion to AD was .813. CONCLUSION: These results suggested that FA values in the right UF might be an effective predictor of conversion of aMCI to AD.",,"Hiyoshi-Taniguchi, K.;Oishi, N.;Namiki, C.;Miyata, J.;Murai, T.;Cichocki, A.;Fukuyama, H.",2015,Sep-Oct,10.1111/jon.12196,0,
3852,An autopsy case of lymphomatosis cerebri showing pathological changes of intravascular large B-cell lymphoma in visceral organs,"We describe the case of a 61-year-old man presenting with subacute encephalopathy. The clinical manifestations included progressive dementia and pyramidal and extrapyramidal tract signs. Brain CT scan and MRI showed diffuse bilateral white matter changes in the cerebral hemispheres, basal ganglia, thalamus and brainstem. No contrast-enhanced lesion was observed. Peripheral blood studies, CSF analysis, and brain and muscle biopsies were nonspecific and failed to reveal diagnostic evidence of any specific disease. The patient was diagnosed with and treated for a cerebral demyelinating disorder. Post mortem examination showed diffuse infiltration of lymphoma cells without mass lesions in the extensive cerebral white and gray matter with minimal intravascular patterns, particularly in the perivascular and periventricular spaces. These findings were consistent with lymphomatosis cerebri (LC). In other visceral organs such as the lungs, liver, kidneys and adrenal glands, blood vessels were plugged by numerous neoplastic cells which were morphologically and immunohistochemically similar to those observed in the CNS, consistent with intravascular malignant lymphoma (IVL). To our knowledge, this is the first autopsy report showing the coexistence of LC and IVL. This case suggests a possible link between LC and IVL. © 2011 Japanese Society of Neuropathology.",CD20 antigen;CD79a antigen;interferon regulatory factor 4;lactate dehydrogenase;lactic acid;methylprednisolone;protein bcl 2;pyruvic acid;adult;alpha rhythm;apathy;arousal;article;autopsy;Babinski reflex;basal ganglion;bradykinesia;brain biopsy;brain stem;bronchopneumonia;cancer infiltration;case report;caudate nucleus;cell infiltration;cerebrospinal fluid analysis;daytime somnolence;delta rhythm;demyelinating disease;diffusion weighted imaging;disorientation;drug megadose;extrapyramidal symptom;gait disorder;gray matter;hand tremor;hemisphere;hepatosplenomegaly;human;hyperreflexia;immunohistochemistry;lactate blood level;lactate dehydrogenase blood level;large cell lymphoma;lethargy;leukoencephalopathy;lymphocytosis;lymphoma cell;lymphomatosis;male;monocyte;multiple organ failure;muscle atrophy;muscle biopsy;myositis;nuclear magnetic resonance imaging;pathological gambling;personality disorder;primary progressive aphasia;priority journal;putamen;pyramidal sign;saccadic eye movement;short term memory;thalamus;walking difficulty;weight reduction;white matter,"Hishikawa, N.;Niwa, H.;Hara, T.;Hara, K.;Ito, M.;Shimada, S.;Yoshida, M.;Hashizume, Y.;Murakami, N.",2011,,,0,
3853,Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome,"Background and purpose: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. Methods: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. Results: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score - Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. Conclusions: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed. Click here to view the accompanying paper in this issue.",aged;Alzheimer disease;article;clinical assessment tool;cognition assessment;controlled study;female;Frontal Assessment Battery and Montreal Cognitive Assessment;Geriatric Depression Scale;Hasegawa Dementia Score Revised;homeostasis model assessment of insulin resistance;human;insulin resistance;major clinical study;male;metabolic syndrome X;Mini Mental State Examination;mood disorder;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;reactive hyperemia index score;retrospective study;risk factor;vascular endothelium;waist circumference;white matter;Archieva,"Hishikawa, N.;Fukui, Y.;Sato, K.;Kono, S.;Yamashita, T.;Ohta, Y.;Deguchi, K.;Abe, K.",2016,,,0,
3854,Diffuse neuroaxonal leukodystrophy with spheroids of adult onset: MRI and pathological studies,"A case of sudanophilic leukoencephalopathy of adult onset was reported. A 42-year-old Japanese woman showed progressive dementia, gait disturbance, apraxia of the left hand, left hemiparesis, and urinary and fecal incontinence. Magnetic resonance imaging (T2-weighted scans and proton images) revealed a symmetrical widespread increase in the signal intensity of cerebral white matter, more prominent in the frontal lobes. Blood levels of very long chain fatty acids and arylsulfatase A were within normal limits. A needle biopsy specimen from the frontal lobe revealed severe demyelination with sudanophilic granules and neurofilament protein-immunoreactive neuroaxonal spheroids in the white matter. The patient's mother was known to have similar symptoms and died at the age of 45, indicating an autosomal dominant inheritance. Because of the dominant inheritance, the psychiatric and neurological symptoms, and the characteristic neuroaxonal spheroids, the case was tentatively diagnosed as 'hereditary diffuse leukoencephalopathy with spheroids', a condition that has not been previously reported in Japan.",,"Hisanaga, K.;Mochizuki, H.;Konno, H.;Saito, A.;Saito, J.;Kitahara, M.;Saito, H.",1997,1997,,0,
3855,Effect of the apolipoprotein E epsilon4 allele on white matter hyperintensities in dementia,"BACKGROUND AND PURPOSE: The clinical significance of the apoE epsilon4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE epsilon4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia. METHODS: The subjects were 131 patients with dementia who had either Alzheimer's disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the epsilon4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases. RESULTS: WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE epsilon4 alleles nor their presence was significantly associated with WMHs before or after control for the potential confounding factors. Multiple logistic regression analyses revealed that age, the presence of hypertension, and the presence of lacunar infarcts were independently associated with WMHs. CONCLUSIONS: The apoE epsilon4 allele was not associated with WMHs in patients with dementia. The fact that WMHs were significantly associated with hypertension and lacunar infarcts may indicate an ischemic origin of WMHs.","Aged;Aged, 80 and over;Alcohol Drinking/epidemiology;*Alleles;Alzheimer Disease/epidemiology/genetics/pathology;Apolipoprotein E4;Apolipoproteins E/*genetics;Axons/*pathology;Brain/*pathology;Brain Ischemia/epidemiology/*pathology;Cerebral Infarction/epidemiology;Dementia/epidemiology/genetics/*pathology;Dementia, Vascular/epidemiology/genetics/pathology;Diabetes Mellitus/epidemiology;Female;Gene Frequency;Genetic Predisposition to Disease;Humans;Hyperlipidemias/epidemiology;Hypertension/epidemiology;Japan/epidemiology;*Magnetic Resonance Imaging;Male;Risk Factors;Smoking/epidemiology","Hirono, N.;Yasuda, M.;Tanimukai, S.;Kitagaki, H.;Mori, E.",2000,Jun,,0,
3856,Impact of white matter changes on clinical manifestation of Alzheimer's disease: A quantitative study,"BACKGROUND AND PURPOSE: There have been conflicting results involving the clinical significance of white matter changes in patients with Alzheimer's disease (AD). We studied the association between the volume of white matter hyperintensities (WMHs) on T2-weighted images and cognitive, neurological, and neuropsychiatric symptoms. METHODS: The subjects were 76 AD patients who had WMHs but no obvious cerebrovascular diseases. We quantified the volume of WMHs by using fast-fluid-attenuated inversion recovery images and whole brain atrophy by using 3D spoiled gradient-echo images. Effects of WMHs and brain atrophy on dementia severity, cognitive function, neuropsychiatric disturbances, and neurological findings were examined. RESULTS: Whole brain atrophy was significantly associated with dementia severity and cognitive disturbances, as well as with grasp reflex and some kinds of neuropsychiatric disturbances. After we controlled for the effects of brain atrophy, duration of symptoms, and demographic factors, we found that WMH volume was not associated with global cognitive disturbances or dementia severity but was significantly associated with urinary incontinence, grasp reflex, and aberrant motor behaviors. Brain atrophy and WMH volume were not significantly correlated either before or after controlling for age, sex, education, and duration of symptoms. WMH volume was associated with hypertension, but brain atrophy was not positively correlated with any vascular risk factors. CONCLUSIONS: Our results support the hypothesis that WMHs in AD patients are superimposed phenomena of vascular origin. WMHs contribute to specific neurological and neuropsychiatric manifestations but not to global cognitive impairment, which is more closely associated with brain atrophy.",Aged;Alzheimer Disease/ pathology;Atrophy;Brain/ pathology;Cognition Disorders/pathology;Female;Hand Strength/physiology;Humans;Magnetic Resonance Angiography;Magnetic Resonance Imaging;Male;Motor Activity/physiology;Urinary Incontinence/pathology,"Hirono, N.;Kitagaki, H.;Kazui, H.;Hashimoto, M.;Mori, E.",2000,Sep,,0,
3857,Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease,"Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled.","Aged;Aged, 80 and over;*Alzheimer Disease/complications/pathology/psychology;Analysis of Variance;Anisotropy;Brain/*pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory Disorders/*etiology;*Memory, Episodic;Mild Cognitive Impairment/pathology;Neuropsychological Tests;*Semantics","Hirni, D. I.;Kivisaari, S. L.;Monsch, A. U.;Taylor, K. I.",2013,Apr,10.1016/j.neuropsychologia.2013.01.013,0,
3858,Trihexyphenidyl (THP)-induced respiratory dyskinesia,"A 63-year-old man developed abnormal respiratory movement during the THP administration for his parkinsonism. Neurological examination on admission showed mild dementia, pseudobulbar signs, orofacial dyskinesia and abnormal respiratory movement, which consisted of rapid and irregular up-and-down movements of the shoulders and thorax especially during expiratory phase. These clinical signs and CT findings (periventricular lucency and multiple small low density spots in the bilateral basal ganglia) indicated the diagnosis of multiple cerebral infarctions. After discontinuing THP, the abnormal respiratory movement and orofacial dyskinesia rapidly disappeared. A trail of THP administration (6 mg/day) provoked the same abnormal respiratory movement, orofacial dyskinesia and choreoathetoid movements in the feet. These abnormal movements were suppressed by the administration of haloperidol and/or sulpiride. These findings suggest that this abnormal respiratory movement and orofacial dyskinesia have a common pharmacological basis, namely relative overactivity of dopaminergic system to cholinergic system in the basal ganglia. Furthermore, an overnight polysomnography disclosed frequent occurrences of sleep apnea of the central type (duration of apnea: 15-30 seconds, the incidence: more than 70 times per night). The respiratory dyskinesia observed in the present case might be caused by a failure of the respiratory control system due to reversible derangement of the dopaminergic and cholinergic systems in the basal ganglia.",trihexyphenidyl;adult;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;dyskinesia;human;intoxication;nervous system;respiration control;respiratory system;sleep disordered breathing,"Hirata, I.;Oda, K.;Kuroda, Y.;Shibasaki, H.",1986,,,0,
3859,Lacunar brain infarction in patients with pseudoxanthoma elasticum,"Brain infarctions in patients with pseudoxanthoma elasticum (PXE) are thought to be associated with the damage of cerebral arteries injured by connective tissue change caused by PXE. We experienced 3 cases of PXE with lacunar brain infarction and evaluated the relationship between the damage of small penetrating arteries and PXE. All patients' diagnosis of PXE were confirmed by histological examination. They were a 47-year-old man and two women with 54 and 62 years of age old. All patients had pseudoxanthoma and angioid streaks and showed pyramidal tract signs. In addition, one patient presented Parkinsonism and another presented involuntary movement of the left lower extremities. None of these cases showed cortical symptoms. Brain CT and MRI revealed multiple lacuna in the areas of penetrating arteries, but their cerebral angiogram were almost normal. Severe small artery diseases, which cannot be attributable only to hypertension, were present. The relationship between such severe small artery disease and damage of the origin of small penetrating arteries caused by PXE was strongly suggested.",article;case report;computer assisted tomography;female;human;male;middle aged;multiinfarct dementia;nuclear magnetic resonance imaging;pseudoxanthoma elasticum,"Hirano, T.;Hashimoto, Y.;Kimura, K.;Uchino, M.",1996,,,0,
3860,Autosomal dominant leukoencephalopathy with mild clinical symptoms due to cerebrovascular dysfunctions: A new disease entity?,"A family with cerebrovascular dysfunctions and extensive white matter lesions was presented. The proband had suffered migraine. His brother showed syncopal episodes and migraine. His mother also suffered severe migraine with aura, and had transient hemiparesis during pregnancy. Their brain MRIs, being quite similar to each other, revealed diffuse bilateral deep white matter lesions, with no changes in serial follow-up. His grandmother showed similar white matter changes on CT, consistent with autosomal dominant inheritance. Lesions were considered to be due to chronic vasogenic edema based upon increased apparent diffusion coefficient (ADC) values on diffusion-weighted imaging, normal spectrum ratio of metabolites on (1)H MR spectroscopy, and decreased regional cerebral blood flows on single-photon emission CT (SPECT). A deficiency of genetically determined factors contributing to the autoregulation of small blood vessels might possibly lead to both clinical symptoms and white matter lesions through the breakdown of the blood-brain barrier and resultant vasogenic edema. Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was suspected, neither NOTCH3 mutation nor granular osmiphilic material (GOM) in the arteriole walls were detected. Further accumulation of similar cases is necessary to establish the possibility of a new familial leukoencephalopathy. © 2007 Elsevier B.V. All rights reserved.",,"Hirabayashi, S.;Wada, T.;Kondo, Y.;Arima, K.",2008,February,,0,
3861,"A 86-year-old woman with dementia, gait and speech disturbance, and right hemiparesis","We report a 86-year-old woman who developed dementia, gait disturbance, speech disturbance, and right hemiparesis. The patient was well until March of 1979 when upon wakening up on one morning she noted slurring of her speech and weakness in her left upper and lower extremities. These symptoms cleared up during the next several months, however, she noted weakness in her left leg again in May 1985. In 1988, her posture became stooped and she walked in small steps. In 1990, she developed memory disturbance and difficulty in naming. In March 1993, she developed weakness in her right hand; she was treated with aspirin and amantadine HCl, however, she deteriorated during the next two week period, and was admitted to our hospital on March 27, 1993. On admission, she appeared alert, however, she could not answer verbally to questions; she could only utter unintelligible sounds. Apparently she was markedly demented. Her blood pressure was 170/98 mmHg, and general physical examination was unremarkable. Cranial nerves were grossly normal except for marked non-fluency in her word expression. She could not stand or walk, and apparently her right upper and lower extremities were paralyzed with some contracture. Deep reflexes were normally active without asymmetry. Chaddock sign was positive bilaterally. Sensory examination was difficult. Pertinent laboratory examination included WBC 13,000/μl, BUN 152mg/dl, creatinine 3.75mg/dl, CRP 20.1mg/dl; a chest X-ray film revealed pneumonic shadow in the upper and the middle right lung fields. Cranial CT scan revealed multiple lacunar infarctions in both basal ganglia and cerebral white matters; periventricular lucency was also noted. She was treated with antibiotics and intravenous fluid. Acid-fast bacilli were recovered from sputum, and she was transferred to another hospital for the treatment of pulmonary tuberculosis. After its treatment she returned to our hospital on July 8, 1993, when her condition was complicated with aspiration pneumonia. On admission, she was semi-comatose, and no intelligible words were heard. Right facial paresis of the central type was noted. She was unable to stand or walk, and her right upper and lower extremities were paretic. Deep reflexes were increased with extensor toe sign on the right. She was treated with chemotherapy and intravenous fluid, however, her clinical course was complicated with respiratory as well as urinary tract infections. She developed cardiac as well as renal failure and expired on September 25, 1993. She was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease, recent large artery thrombosis in the territory of the left internal carotid artery, renal failure, cardiac failure, hepatic failure, and pneumonia. Post-mortem examination revealed sclerosing glomerulonephritis, pneumonia, a small fresh myocardial infarction, and severe atherosclerosis in the aorta. In the central nervous system, 50 to 70% narrowing was noted in the left middle cerebral artery. An old cerebral infarction was involving the subcortical region of the left frontal lobe extending into the caudate nucleus as well as putamen. The question was whether or not the patient had motor aphasia. Evaluation was a bit difficult because of concomitant dementia. Some participants ascribed her severe non-fluency to combined lesions in the white matter that lies next to the body of the lateral ventricle and that lies in the lateral aspect of the anterior horn.",acetylsalicylic acid;amantadine;aged;aorta atherosclerosis;artery thrombosis;article;Binswanger encephalopathy;brain infarction;case report;dementia;female;gait disorder;glomerulonephritis;heart failure;heart infarction;hemiparesis;human;kidney failure;liver failure;pneumonia;speech disorder,"Hirabayashi, K.;Morikawa, N.;Mori, H.;Miyake, T.;Suda, K.;Kondo, T.;Mizuno, Y.",1995,,,0,
3862,Longitudinally extensive spinal cord infarction in CADASIL,,CADASIL;case report;complication;female;human;infarction;middle aged;nuclear magnetic resonance imaging;spastic paraplegia;pathology;spinal cord disease,"Hinze, S.;Goonasekera, M.;Nannucci, S.;Quaghebeur, G.;Briley, D.;Markus, H. S.;Sen, A.",2015,,,0,
3863,Molecular disorganization of axons adjacent to human lacunar infarcts,"Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by approximately 20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is increased. Myelin basic protein and neurofilament immunolabelling demonstrates that axons in these adjacent regions have preserved axonal cytoskeleton organization and are generally myelinated. This indicates that the loss of normal axonal microdomain architecture results from disrupted axoglial signalling in white matter adjacent to lacunar and microinfarcts. The loss of the normal molecular organization of nodes and paranodes is associated with axonal degeneration and may lead to impaired conduction velocity across surviving axons after stroke. These findings demonstrate that the degree of white matter injury associated with cerebral microvascular disease extends well beyond what can be identified using imaging techniques and that an improved understanding of the neurobiology in these regions can drive new therapeutic strategies for this disease entity.","Aged;Aged, 80 and over;Axons/pathology;Brain/ metabolism/ pathology;Cell Adhesion Molecules, Neuronal/metabolism;Citrullinemia/pathology;Female;Humans;Leukoencephalopathies/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Basic Protein/metabolism;Nerve Fibers, Myelinated/ pathology;Neurofilament Proteins/metabolism;Ranvier's Nodes/metabolism/pathology;Spectrin/metabolism;Stroke, Lacunar/complications/ pathology","Hinman, J. D.;Lee, M. D.;Tung, S.;Vinters, H. V.;Carmichael, S. T.",2015,Mar,10.1093/brain/awu398,0,
3864,Investigation of whole brain irradiation for brain metastases from lung cancer,"Brain metastases are generally poor prognosis, but makes long-term survival with progress of the treatment. An effect and influence of whole brain irradiation for brain metastases from lung cancer was investigated. Whole brain irradiation was useful as palliative treatment. White matter change after the treatment was accepted and dementia was doubted, too. Dementia was included in the change by brain metastases, and it was thought that evaluation by MRI was necessary.",article;brain metastasis;brain radiation;cancer grading;dementia;human;lung cancer;Mini Mental State Examination;nuclear magnetic resonance imaging;palliative therapy;white matter,"Himei, K.;Nagano, H.;Yabuki, T.;Shiode, T.;Hashimura, S.;Hayashi, H.;Watanabe, Y.;Baba, Y.",2009,,,0,
3865,Antiphospholipid antibody syndrome: a case study,"Antiphospholipid antibody syndrome includes a spectrum of autoantibody reactions associated with vascular thrombosis, thrombocytopenia and recurrent fetal loss. Neurologic manifestations include strokes, transient ischemic attacks and multi-infarct dementia. Treatment involves prolonged anticoagulation, and prognosis is poor. A case study of a 21-year-old female with antiphospholipid antibody syndrome is provided.",anticoagulant agent;steroid;adult;antiphospholipid syndrome;article;blood clotting test;case report;electroencephalography;female;hemiplegia;human;nuclear magnetic resonance imaging;nursing;patient care planning,"Hilton, G.;Revese, E. R.;Madayag, M. D.",1992,,,0,
3866,Titanium cranioplasty and the prediction of complications,"Objectives. Titanium cranioplasty (TC), the operative repair of a skull defect with an ergonomically manufactured plate to restore cosmesis, cranial function and reduce complications is a common neurosurgical procedure. It is technically simple but has high complication rates. This study aimed to determine the incidence and predictors of complications following TC. Design. Retrospective review. Subjects. All patients undergoing TC over a 42-month period in our institution. Methods. Data was collected from the hospital database and case-notes. 3D CT reconstructions accurately measured defect size and location. Statistical analysis included correlation, independent variable analysis and descriptive methods. Results. A total of 95 TCs were analysed in 92 patients (3 cases of bifrontal cranioplasty). The commonest indications for TC were bony defect following removal of infected bone flap (n =20), acute subdural haematoma (n =18) and post-malignant infarction (n =11). The commonest site was frontotemporoparietal (n =61) and the overall complication rate was 30.4%. The commonest complication was infection and the overall removal rate was 8.4%. The mean cranioplasty area was 73.26 cm2 (range 12.78-178.26 cm 2). There was a significant relationship between area and length of post-operative hospital stay (p =0.008, Pearson Rank). There was no significant relationship between area and complications, removal rates or infections. There was no relationship between age and total complications, post-operative hospital stay and infections. There was a non-significant trend for older patients to have their cranioplasty removed. Conclusions. TC size is predictive of postoperative length of stay. However, the TC size is not predictive of complications or removal rate. Also, there was no association between interval since primary operation and complications. There was a non-significant trend for greater rates of TC removal in the elderly. There were no predictors of complications identified but they are common and patients should be consented accordingly. © 2012 The Neurosurgical Foundation.",titanium;adult;aged;article;bifrontal cranioplasty;bone graft;brain infarction;computer assisted tomography;cranioplasty;decompressive craniectomy;female;frontotemporal dementia;hospitalization;human;image reconstruction;infection complication;length of stay;major clinical study;male;postmalignant infarction;postoperative period;prediction;priority journal;retrospective study;subdural hematoma;titanium cranioplasty;treatment duration,"Hill, C. S.;Luoma, A. M. V.;Wilson, S. R.;Kitchen, N.",2012,,,0,
3867,Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome,"The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serum is considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomograpy (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE).",,"Hilker, R.;Thiel, A.;Geisen, C.;Rudolf, J.",2000,2000,,0,
3868,Intracranial stenosis in cognitive impairment and dementia,"Intracranial stenosis is a common vascular lesion observed in Asian and other non-Caucasian stroke populations. However, its role in cognitive impairment and dementia has been under-studied. We, therefore, examined the association of intracranial stenosis with cognitive impairment, dementia and their subtypes in a memory clinic case-control study, where all subjects underwent detailed neuropsychological assessment and 3 T neuroimaging including three-dimensional time-of-flight magnetic resonance angiography. Intracranial stenosis was defined as ≥50% narrowing in any of the intracranial arteries. A total of 424 subjects were recruited of whom 97 were classified as no cognitive impairment, 107 as cognitive impairment no dementia, 70 vascular cognitive impairment no dementia, 121 Alzheimer’s Disease, and 30 vascular dementia. Intracranial stenosis was associated with dementia (age/gender/education – adjusted odds ratios (OR): 4.73, 95% confidence interval (CI): 1.93–11.60) and vascular cognitive impairment no dementia (OR: 3.98, 95% CI: 1.59–9.93). These associations were independent of cardiovascular risk factors and MRI markers. However, the association with Alzheimer’s Disease and vascular dementia became attenuated in the presence of white matter hyperintensities. Intracranial stenosis is associated with vascular cognitive impairment no dementia independent of MRI markers. In Alzheimer’s Disease and vascular dementia, this association is mediated by cerebrovascular disease. Future studies focusing on perfusion and functional markers are needed to determine the pathophysiological mechanism(s) linking intracranial stenosis and cognition so as to identify treatment strategies.",aged;Alzheimer disease;artery occlusion;article;body mass;brain artery;brain perfusion;case control study;cognitive defect;controlled study;dementia;executive function test;female;human;magnetic resonance angiography;male;mean arterial pressure;Mini Mental State Examination;Montreal cognitive assessment;neuropsychological test;prevalence;priority journal;questionnaire;verbal memory test,"Hilal, S.;Xu, X.;Ikram, M. K.;Vrooman, H.;Venketasubramanian, N.;Chen, C.",2017,,10.1177/0271678x16663752,0,3869
3869,Intracranial stenosis in cognitive impairment and dementia,"Intracranial stenosis is a common vascular lesion observed in Asian and other non-Caucasian stroke populations. However, its role in cognitive impairment and dementia has been under-studied. We, therefore, examined the association of intracranial stenosis with cognitive impairment, dementia and their subtypes in a memory clinic case-control study, where all subjects underwent detailed neuropsychological assessment and 3 T neuroimaging including three-dimensional time-of-flight magnetic resonance angiography. Intracranial stenosis was defined as >/=50% narrowing in any of the intracranial arteries. A total of 424 subjects were recruited of whom 97 were classified as no cognitive impairment, 107 as cognitive impairment no dementia, 70 vascular cognitive impairment no dementia, 121 Alzheimer's Disease, and 30 vascular dementia. Intracranial stenosis was associated with dementia (age/gender/education - adjusted odds ratios (OR): 4.73, 95% confidence interval (CI): 1.93-11.60) and vascular cognitive impairment no dementia (OR: 3.98, 95% CI: 1.59-9.93). These associations were independent of cardiovascular risk factors and MRI markers. However, the association with Alzheimer's Disease and vascular dementia became attenuated in the presence of white matter hyperintensities. Intracranial stenosis is associated with vascular cognitive impairment no dementia independent of MRI markers. In Alzheimer's Disease and vascular dementia, this association is mediated by cerebrovascular disease. Future studies focusing on perfusion and functional markers are needed to determine the pathophysiological mechanism(s) linking intracranial stenosis and cognition so as to identify treatment strategies.",Cognitive impairment;cerebrovascular diseases;dementia;intracranial stenosis;magnetic resonance angiography,"Hilal, S.;Xu, X.;Ikram, M. K.;Vrooman, H.;Venketasubramanian, N.;Chen, C.",2016,Aug 3,10.1177/0271678x16663752,0,
3870,Risk Factors and Consequences of Cortical Thickness in an Asian Population,"Cortical thickness has been suggested to be one of the most important markers of cortical atrophy. In this study, we examined potential risk factors of cortical thickness and its association with cognition in an elderly Asian population from Singapore. This is a cross-sectional study among 572 Chinese and Malay patients from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study, who underwent comprehensive examinations including neuropsychological testing and brain magnetic resonance imaging (MRI). Cortical thickness (in micrometers) was measured using a model-based automated procedure. Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment was categorized into cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia in accordance with accepted criteria. Linear regression models were used to examine the association between various risk factors and cortical thickness. With respect to cognition as outcome, both linear (for Z-scores) and logistic (for CIND/dementia) regression models were constructed. Initial adjustments were made for age, sex, and education, and subsequently for other cardiovascular risk factors and MRI markers. Out of 572 included patients, 171 (29.9%) were diagnosed with CIND-mild, 197 (34.4%) with CIND-moderate, and 28 (4.9%) with dementia. Risk factors related to a smaller cortical thickness were increased age, male sex, Malay ethnicity, higher blood glucose, and body mass index levels and presence of lacunar infarcts on MRI. Smaller cortical thickness was associated with CIND moderate/dementia [odds ratio (OR) per standard deviation (SD) decrease: 1.70; 95% confidence interval (CI): 1.19-2.44, P=0.004] and with composite Z-score reflecting global cognitive functioning [mean difference per SD decrease: -0.094; 95% CI: -0.159; -0.030, P=0.004]. In particular, smaller cortical thicknesses in the occipital and temporal lobes were related to cognitive impairment. Finally, in terms of specific cognitive domains, the most significant associations were found for executive function, visuoconstruction, and visual memory. Smaller cortical thickness is significantly associated with cognitive impairment, suggesting a contribution of diffuse cortical atrophy beyond the medial temporal lobe to cognitive function. These findings suggest that cortical thinning is a biomarker of neurodegenerative changes in the brain not only in dementia, but also in its preclinical stages.",glucose;age distribution;aged;article;Asian;body mass;cardiovascular risk;Chinese;cognition;cognitive defect;cortical thickness (brain);cross-sectional study;dementia;demography;educational status;ethnic difference;executive function;female;glucose blood level;human;lacunar stroke;major clinical study;Malay (people);male;medial temporal lobe;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;occipital lobe;priority journal;risk factor;sex difference;Singapore;temporal lobe;visual memory,"Hilal, S.;Xin, X.;Ang, S. L.;Tan, C. S.;Venketasubramanian, N.;Niessen, W. J.;Vrooman, H.;Wong, T. Y.;Chen, C.;Ikram, M. K.",2015,,10.1097/md.0000000000000852,0,3871
3871,Risk Factors and Consequences of Cortical Thickness in an Asian Population,"Cortical thickness has been suggested to be one of the most important markers of cortical atrophy. In this study, we examined potential risk factors of cortical thickness and its association with cognition in an elderly Asian population from Singapore. This is a cross-sectional study among 572 Chinese and Malay patients from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study, who underwent comprehensive examinations including neuropsychological testing and brain magnetic resonance imaging (MRI). Cortical thickness (in micrometers) was measured using a model-based automated procedure. Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment was categorized into cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia in accordance with accepted criteria. Linear regression models were used to examine the association between various risk factors and cortical thickness. With respect to cognition as outcome, both linear (for Z-scores) and logistic (for CIND/dementia) regression models were constructed. Initial adjustments were made for age, sex, and education, and subsequently for other cardiovascular risk factors and MRI markers. Out of 572 included patients, 171 (29.9%) were diagnosed with CIND-mild, 197 (34.4%) with CIND-moderate, and 28 (4.9%) with dementia. Risk factors related to a smaller cortical thickness were increased age, male sex, Malay ethnicity, higher blood glucose, and body mass index levels and presence of lacunar infarcts on MRI. Smaller cortical thickness was associated with CIND moderate/dementia [odds ratio (OR) per standard deviation (SD) decrease: 1.70; 95% confidence interval (CI): 1.19-2.44, P=0.004] and with composite Z-score reflecting global cognitive functioning [mean difference per SD decrease: -0.094; 95% CI: -0.159; -0.030, P=0.004]. In particular, smaller cortical thicknesses in the occipital and temporal lobes were related to cognitive impairment. Finally, in terms of specific cognitive domains, the most significant associations were found for executive function, visuoconstruction, and visual memory. Smaller cortical thickness is significantly associated with cognitive impairment, suggesting a contribution of diffuse cortical atrophy beyond the medial temporal lobe to cognitive function. These findings suggest that cortical thinning is a biomarker of neurodegenerative changes in the brain not only in dementia, but also in its preclinical stages.",,"Hilal, S.;Xin, X.;Ang, S. L.;Tan, C. S.;Venketasubramanian, N.;Niessen, W. J.;Vrooman, H.;Wong, T. Y.;Chen, C.;Ikram, M. K.",2015,7,,0,
3872,Cortical cerebral microinfarcts on 3T MRI: A novel marker of cerebrovascular disease,"Objective: We examined the risk factors of cortical cerebral microinfarcts (CMIs) on 3T MRI and their association with cognitive impairment. Methods: Participants (aged 60 years and older) from the multiethnic Epidemiology of Dementia In Singapore Study underwent detailed neuropsychological testing and 3T brain MRI. Cortical CMIs were graded using a previously validated protocol. Cognitive impairment was categorized into cognitive impairment, no dementia (CIND)-mild, CIND-moderate, and dementia. Cognitive function was summarized as composite and domain-specific z scores. Results: Among 861 participants, 54 (6.3%) had ≥1 cortical CMI. In multivariate-adjusted models, the risk factors of cortical CMIs were increasing age, Malay ethnicity, hypertension, diabetes, history of stroke, and markers of both large (cortical infarcts and intracranial stenosis) and small (lacunar infarcts, white matter hyperintensities, cerebral microbleeds) vessel disease. Presence of cortical CMIs was associated with CIND-moderate (odds ratio: 3.12; 95% confidence interval [CI]: 1.18-8.58), dementia (odds ratio: 16.92; 95% CI: 3.37-85.05), and poorer cognitive function (mean difference in composite z score: -0.42; 95% CI: -0.62 to -0.21). Additional adjustments for vascular risk factors and other MRI markers did not alter these associations. Conclusions: Cortical CMIs are a novel MRI marker of cerebrovascular disease and are independently associated with cognitive impairment and dementia. These findings provide new insights into the burden of cerebrovascular disease in cognitive impairment. Future research is needed to establish the additional etiologic and prognostic significance of cortical CMIs.",biological marker;aged;article;body mass;Boston naming test;brain infarction;cerebrovascular accident;cognitive defect;cortical cerebral microinfarct;dementia;diabetes mellitus;disease association;DSM-IV;executive function;female;human;hyperlipidemia;hypertension;major clinical study;male;medical history;medical record;mental test;Mini Mental State Examination;Montreal cognitive assessment;neuroimaging;nuclear magnetic resonance imaging;priority journal;risk factor;social status;susceptibility weighted imaging;verbal memory;visual memory;Wechsler adult intelligence scale;Wechsler memory scale;word list recall,"Hilal, S.;Sikking, E.;Shaik, M. A.;Chan, Q. L.;Van Veluw, S. J.;Vrooman, H.;Cheng, C. Y.;Sabanayagam, C.;Cheung, C. Y.;Wong, T. Y.;Venketasubramanian, N.;Biessels, G. J.;Chen, C.;Ikram, M. K.",2016,,10.1212/wnl.0000000000003110,0,3873
3873,Cortical cerebral microinfarcts on 3T MRI: A novel marker of cerebrovascular disease,"OBJECTIVE: We examined the risk factors of cortical cerebral microinfarcts (CMIs) on 3T MRI and their association with cognitive impairment. METHODS: Participants (aged 60 years and older) from the multiethnic Epidemiology of Dementia In Singapore Study underwent detailed neuropsychological testing and 3T brain MRI. Cortical CMIs were graded using a previously validated protocol. Cognitive impairment was categorized into cognitive impairment, no dementia (CIND)-mild, CIND-moderate, and dementia. Cognitive function was summarized as composite and domain-specific z scores. RESULTS: Among 861 participants, 54 (6.3%) had >/=1 cortical CMI. In multivariate-adjusted models, the risk factors of cortical CMIs were increasing age, Malay ethnicity, hypertension, diabetes, history of stroke, and markers of both large (cortical infarcts and intracranial stenosis) and small (lacunar infarcts, white matter hyperintensities, cerebral microbleeds) vessel disease. Presence of cortical CMIs was associated with CIND-moderate (odds ratio: 3.12; 95% confidence interval [CI]: 1.18-8.58), dementia (odds ratio: 16.92; 95% CI: 3.37-85.05), and poorer cognitive function (mean difference in composite z score: -0.42; 95% CI: -0.62 to -0.21). Additional adjustments for vascular risk factors and other MRI markers did not alter these associations. CONCLUSIONS: Cortical CMIs are a novel MRI marker of cerebrovascular disease and are independently associated with cognitive impairment and dementia. These findings provide new insights into the burden of cerebrovascular disease in cognitive impairment. Future research is needed to establish the additional etiologic and prognostic significance of cortical CMIs.",,"Hilal, S.;Sikking, E.;Shaik, M. A.;Chan, Q. L.;van Veluw, S. J.;Vrooman, H.;Cheng, C. Y.;Sabanayagam, C.;Cheung, C. Y.;Wong, T. Y.;Venketasubramanian, N.;Biessels, G. J.;Chen, C.;Ikram, M. K.",2016,Sep 2,10.1212/wnl.0000000000003110,0,
3874,Cerebral microbleeds and cognition: The epidemiology of dementia in singapore study,"Cerebral microbleeds (CMBs) are considered to be a novel marker of cerebral small vessel disease. However, the link with cognitive impairment remains unclear. We investigated whether CMBs - independent of other traditional markers of cerebral small vessel disease - are related to cognition. Chinese subjects from the population-based Singapore Chinese Eye Study, who failed an initial cognitive screening and were recruited into the ongoing Epidemiology of Dementia in Singapore Study, underwent neuropsychological testing and 3 T brain magnetic resonance imaging. The presence and number of CMBs were graded using Brain Observer Microbleed Scale on susceptibility-weighted images. Other magnetic resonance imaging lesions that were graded included presence of lacunes, white matter lesion, and total brain volumes. A comprehensive neuropsychological battery was administered and cognitive function was summarized as composite and domain-specific Z-scores. Among 282 subjects, 91 had any CMBs (32.3%), of whom 36 (12.8%) had multiple CMBs. CMBs were - independent of cardiovascular risk factors and other markers of cerebral small vessel disease - significantly associated with poorer cognitive function as reflected by composite Z-score (mean difference per CMB increase: -0.06; 95% confidence interval: -0.11, -0.01] and with domain-specific Z-scores including executive function, attention, and visuoconstruction. Among Chinese subjects CMBs were, independent of other concomitant markers of cerebral small vessel disease, associated with poorer cognitive function. Copyright © 2013 by Lippincott Williams & Wilkins.",,"Hilal, S.;Saini, M.;Tan, C. S.;Catindig, J. A.;Koay, W. I.;Niessen, W. J.;Vrooman, H. A.;Wong, T. Y.;Chen, C.;Ikram, M. K.;Venketasubramanian, N.",2014,April-June,,0,
3875,"Ankle-brachial index, cognitive impairment and cerebrovascular disease in a Chinese population","BACKGROUND: Previous studies have assessed the association between ankle-brachial index (ABI) and cognition, mainly using brief cognitive tests. We investigated whether ABI was associated with cognition independent of neuroimaging markers of cerebrovascular disease. METHODS: Chinese subjects (n = 278, aged >/=60 years) were recruited from the ongoing Epidemiology of Dementia in Singapore (EDIS) Study. Ankle and brachial blood pressures were measured, and low ABI was defined as </=0.9. A neuropsychological battery was utilized to determine cognition. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to standard diagnostic criteria. Magnetic resonance imaging (MRI) was used to obtain semiquantitative and quantitative markers of cerebrovascular disease and atrophy. RESULTS: A low ABI was related to the presence of intracranial stenosis (odds ratio, OR = 1.71; 95% confidence interval, CI: 1.13-2.59), but not with the presence of infarcts, microbleeds or grey matter, white matter and white matter lesion volumes. Furthermore, a low ABI was associated with poorer overall cognitive function and CIND-moderate/dementia (OR = 2.26; 95% CI: 1.11-4.59), independent of cardiovascular risk factors, and the MRI markers related to cerebrovascular disease and atrophy. CONCLUSION: We found an association between a low ABI and cognitive impairment, independent of any MRI marker of cerebral small vessel disease or large artery atherosclerotic disease.","Aged;Ankle Brachial Index;Cerebrovascular Disorders/ diagnosis;China;Cognition Disorders/ diagnosis;Constriction, Pathologic;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests","Hilal, S.;Saini, M.;Tan, C. S.;Catindig, J. A.;Dong, Y. H.;Leon, L. B.;Niessen, W. J.;Vrooman, H.;Wong, T. Y.;Chen, C.;Venketasubramanian, N.;Ikram, M. K.",2014,,10.1159/000357372,0,
3876,"Intracranial stenosis, cerebrovascular diseases, and cognitive impairment in Chinese","Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS:-0.37 (95% confidence interval:-0.63,-0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.",,"Hilal, S.;Saini, M.;Tan, C. S.;Catindig, J. A.;Dong, Y. H.;Holandez, R. L.;Niessen, W. J.;Vrooman, H. A.;Ting, E.;Wong, T. Y.;Chen, C.;Venketasubramanian, N.;Ikram, M. K.",2015,6,,0,
3877,Microvascular network alterations in retina of subjects with cerebral small vessel disease,"Novel retinal imaging techniques have enabled the assessment of quantitative vascular parameters, which provide information on the microvasculature before the appearance of retinopathy signs. Advances in neuroimaging have revealed that cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions (WML) - may be a novel marker of cerebral small vessel disease. We examine whether quantitative retinal vascular parameters are related to cerebral small vessel disease in a Chinese population. Participants from Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial magnetic resonance imaging and retinal-photography. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from photographs using a semi-automated computer-assisted program. Lacunar infarcts and CMB were visually graded. Total brain and WML volume were obtained using a validated segmentation tool. A total of 261 subjects were included, of whom 36 had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted models, narrower retinal arteriolar caliber, wider venular caliber and smaller arteriolar fractal dimension were associated with presence of multiple CMB. In contrast, no association was found with lacunar infarcts and WML volume. After multivariate adjustments, associations of venular caliber, arteriolar fractal dimensions and arteriolar tortuosity with CMB remained statistically significant. In conclusion, subjects with early structural changes in retinal microvasculature were more likely to have CMBs, supporting hypothesis that CMB may be an early manifestation of cerebral small vessel disease.",Aged;Biomarkers;Brain/pathology;Brain Infarction/epidemiology/pathology;Cerebral Small Vessel Diseases/epidemiology/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Microvessels/ pathology;Retinal Vessels/ pathology;Risk Factors;White Matter/pathology,"Hilal, S.;Ong, Y. T.;Cheung, C. Y.;Tan, C. S.;Venketasubramanian, N.;Niessen, W. J.;Vrooman, H.;Anuar, A. R.;Chew, M.;Chen, C.;Wong, T. Y.;Ikram, M. K.",2014,Aug 8,10.1016/j.neulet.2014.06.024,0,
3878,Association Between Subclinical Cardiac Biomarkers and Clinically Manifest Cardiac Diseases With Cortical Cerebral Microinfarcts,"Importance: Subclinical and clinical cardiac diseases have been previously linked to magnetic resonance imaging (MRI) manifestations of cerebrovascular disease, such as lacunes and white matter hyperintensities, as well as dementia. Cortical cerebral microinfarcts (CMIs), a novel MRI marker of cerebral vascular disease, have not been studied, to date, in relation to subclinical and clinical cardiac diseases. Objective: To examine the association of blood biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases with CMIs graded on 3-T MRI in a memory clinic population. Design, Setting, and Participants: This baseline cross-sectional analysis of a cohort study performed from August 12, 2010, to July 28, 2015, included 464 memory clinic participants. All participants underwent collection of blood samples, neuropsychological assessment, and 3-T MRI. Exposures: N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations were measured by electrochemiluminescence immunoassays. Cardiac disease was defined as a history of atrial fibrillation, ischemic heart diseases, or congestive heart failure. Main Outcomes and Measures: The CMIs were graded according to a previously validated protocol. Results: Of 464 participants, 124 had insufficient blood plasma samples and 97 had no CMI grading (none, incomplete, or ungradable MRI), leaving a sample size of 243 for final analysis (mean [SD] age, 72.8 [9.1] years; 116 men [42.9%]). Seventy participants (28.8%) had cortical CMIs (median, 1; range, 0-43). Compared with participants with no CMIs, those with CMIs had a significantly higher prevalence of atrial fibrillation (rate ratio [RR], 1.62; 95% CI, 1.20-21.8), ischemic heart disease (RR, 4.31; 95% CI, 3.38-5.49), and congestive heart failure (RR, 2.05; 95% CI, 1.29-3.25). Significantly higher levels of NT-proBNP (RR, 3.16; 95% CI, 2.33-4.27) and hs-cTnT (RR, 2.17; 95% CI, 1.00-4.74) were found in participants with CMIs. In multivariate models adjusted for demographics and vascular risk factors, higher levels of NT-proBNP (RR, 3.19; 95% CI, 2.62-3.90) and hs-cTnT (RR, 4.86; 95% CI, 3.03-7.08) were associated with CMIs. These associations persisted even after excluding patients with clinically manifest cardiac disease. Conclusions and Relevance: This study found that biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases were associated with CMIs on 3-T MRI in patients attending a memory clinic, suggesting that cardiac disease may contribute to the development of CMIs. Hence, cardiac dysfunction should be targeted as a potentially modifiable factor to prevent CMI-related brain injury.","0 (Peptide Fragments);0 (Troponin T);0 (pro-brain natriuretic peptide (1-76));114471-18-0 (Natriuretic Peptide, Brain);Aged;Aged, 80 and over;Atrophy/diagnostic imaging/etiology;Cerebral Cortex/diagnostic imaging/ pathology;Cognition Disorders/etiology;Cohort Studies;Cross-Sectional Studies;Female;Heart Diseases/blood/complications/diagnostic imaging;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Middle Aged;Natriuretic Peptide, Brain/ blood;Peptide Fragments/ blood;Troponin T/ blood","Hilal, S.;Chai, Y. L.;van Veluw, S.;Shaik, M. A.;Ikram, M. K.;Venketasubramanian, N.;Richards, A. M.;Biessels, G. J.;Chen, C.",2017,Apr 1,,0,3879
3879,Association Between Subclinical Cardiac Biomarkers and Clinically Manifest Cardiac Diseases With Cortical Cerebral Microinfarcts,"Importance: Subclinical and clinical cardiac diseases have been previously linked to magnetic resonance imaging (MRI) manifestations of cerebrovascular disease, such as lacunes and white matter hyperintensities, as well as dementia. Cortical cerebral microinfarcts (CMIs), a novel MRI marker of cerebral vascular disease, have not been studied, to date, in relation to subclinical and clinical cardiac diseases. Objective: To examine the association of blood biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases with CMIs graded on 3-T MRI in a memory clinic population. Design, Setting, and Participants: This baseline cross-sectional analysis of a cohort study performed from August 12, 2010, to July 28, 2015, included 464 memory clinic participants. All participants underwent collection of blood samples, neuropsychological assessment, and 3-T MRI. Exposures: N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations were measured by electrochemiluminescence immunoassays. Cardiac disease was defined as a history of atrial fibrillation, ischemic heart diseases, or congestive heart failure. Main Outcomes and Measures: The CMIs were graded according to a previously validated protocol. Results: Of 464 participants, 124 had insufficient blood plasma samples and 97 had no CMI grading (none, incomplete, or ungradable MRI), leaving a sample size of 243 for final analysis (mean [SD] age, 72.8 [9.1] years; 116 men [42.9%]). Seventy participants (28.8%) had cortical CMIs (median, 1; range, 0-43). Compared with participants with no CMIs, those with CMIs had a significantly higher prevalence of atrial fibrillation (rate ratio [RR], 1.62; 95% CI, 1.20-21.8), ischemic heart disease (RR, 4.31; 95% CI, 3.38-5.49), and congestive heart failure (RR, 2.05; 95% CI, 1.29-3.25). Significantly higher levels of NT-proBNP (RR, 3.16; 95% CI, 2.33-4.27) and hs-cTnT (RR, 2.17; 95% CI, 1.00-4.74) were found in participants with CMIs. In multivariate models adjusted for demographics and vascular risk factors, higher levels of NT-proBNP (RR, 3.19; 95% CI, 2.62-3.90) and hs-cTnT (RR, 4.86; 95% CI, 3.03-7.08) were associated with CMIs. These associations persisted even after excluding patients with clinically manifest cardiac disease. Conclusions and Relevance: This study found that biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases were associated with CMIs on 3-T MRI in patients attending a memory clinic, suggesting that cardiac disease may contribute to the development of CMIs. Hence, cardiac dysfunction should be targeted as a potentially modifiable factor to prevent CMI-related brain injury.",,"Hilal, S.;Chai, Y. L.;van Veluw, S.;Shaik, M. A.;Ikram, M. K.;Venketasubramanian, N.;Richards, A. M.;Biessels, G. J.;Chen, C.",2017,Feb 06,,0,
3880,Markers of cardiac dysfunction in cognitive impairment and dementia,"Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD).We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia.A case-control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64-49.79) and dementia (OR: 16.89; 95%CI: 2.02-142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23-48.58). These associations were independent of other vascular risk factors.In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD.",amino terminal pro brain natriuretic peptide;troponin T;Age Related White Matter Changes Scale;aged;article;assessment of humans;brain infarction;case control study;cerebrovascular disease;cognitive defect;congestive heart failure;controlled study;dementia;diabetes mellitus;disease association;female;atrial fibrillation;heart disease;heart infarction;human;hypertension;major clinical study;male;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;protein blood level;white matter lesion;Magnetom Trio Tim,"Hilal, S.;Chai, Y. L.;Ikram, M. K.;Elangovan, S.;Yeow, T. B.;Xin, X.;Chong, J. Y.;Venketasubramanian, N.;Richards, A. M.;Chong, J. P. C.;Lai, M. K. P.;Chen, C.",2015,,,0,
3881,Subcortical Atrophy in Cognitive Impairment and Dementia,"BACKGROUND: Cortical atrophy is a key neuroimaging feature of dementia. However, the role of subcortical gray matter reduction in cognitive impairment has not been explored extensively. OBJECTIVES: We examined the risk factors of subcortical structures on neuroimaging and their association with cognitive impairment and dementia. METHODS: Data from two studies were used: a subsample from the Epidemiology of Dementia in Singapore (EDIS) study of non-demented community-dwelling subjects (n = 550) and a case-control study. Subjects underwent similar neuropsychological tests and brain MRI. Subcortical volumes of accumbens, amygdala, caudate, pallidum, putamen, thalamus, hippocampus, and brainstem were measured. Cognitive impairment no dementia (CIND), dementia and its subtypes, vascular cognitive impairment (VCI), were defined using accepted criteria. Cognitive function was also expressed as both composite and domain-specific Z-scores. RESULTS: In the EDIS study, age, female gender, Malay ethnicity, diabetes, lacunar-infarcts, and white matter lesions were the most important risk factors for subcortical atrophy. Moreover, smaller volumes of accumbens, amygdala, caudate, thalamus, and brainstem were significantly associated with lower cognitive composite Z-scores. With respect to clinical outcomes in the case-control study, structures such as the accumbens, caudate, putamen, and hippocampus were associated with both CIND and dementia. Smaller caudate and pallidum volumes were related to VCI whereas amygdalar atrophy was only associated with non-VCI. Furthermore, subcortical atrophy was related to both VCI and non-VCI. CONCLUSION: Subcortical gray matter atrophy is not only observed in dementia, but also in the preclinical stages of cognitive impairment. Furthermore, besides VCI, subcortical structures were also related to non-VCI.",,"Hilal, S.;Amin, S. M.;Venketasubramanian, N.;Niessen, W. J.;Vrooman, H.;Wong, T. Y.;Chen, C.;Ikram, M. K.",2015,,10.3233/jad-150473,0,
3882,"Plasma Amyloid-β Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study","Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ 1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ 1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementia Objective: To examine the association of plasma Aβ levels (i.e., Aβ1-38, Aβ 1-40, and Aβ 1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. Methods: We analyzed plasma A-1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Aβ levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-Analysis with fixed effects. Results: Higher levels of plasma Aβ 1-38, Aβ 1-40, Aβ 1-42, and Aβ 1-40/ Aβ 1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels ofAβ1-40 andAβ 1-40/ Aβ1-42 were significantly associated with largerWMH volumes. With regard to cognition, a higher level of Aβ 1-38 Aβ 1-40 and Aβ 1-40/ Aβ 1-42 was related to worse performance on cognitive test specifically in memory domain. Conclusion: Higher plasma levels of Aβ levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Aβ levels thus mark the presence of vascular brain pathology.",nuclear magnetic resonance scanner;VISION MR;amyloid beta protein;amyloid beta protein[1-38];amyloid beta protein[1-40];amyloid beta protein[1-42];antihypertensive agent;apolipoprotein E;edetic acid;unclassified drug;adult;aged;antihypertensive therapy;article;cerebrovascular disease;cognitive defect;cohort analysis;female;human;hypertension;ischemic heart disease;major clinical study;male;mean arterial pressure;memory;middle aged;neuroimaging;neuropathology;nuclear magnetic resonance imaging;priority journal;protein blood level;recognition;risk assessment;smoking,"Hilal, S.;Akoudad, S.;Van Duijn, C. M.;Niessen, W. J.;Verbeek, M. M.;Vanderstichele, H.;Stoops, E.;Arfan Ikram, M.;Vernooij, M. W.",2017,,10.3233/jad-170458,0,
3883,Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies,"Cerebral glucose metabolism using positron emission tomography (PET) with (18)F-fluorodeoxyglucose was examined in 11 patients with probable Alzheimer's disease (AD), 6 patients with probable, and 1 patient with autopsy-confirmed dementia with Lewy bodies (DLB) as well as in 10 age-matched normal control subjects. Among widespread cortical regions showing glucose hypometabolism in the DLB group, the metabolic reduction was most pronounced in the visual association cortex compared to that in the AD group. Using a metabolic ratio of 0.92 in the visual association cortex as a cutoff (mean-2 SD of normal control subjects), DLB could be distinguished from AD with a sensitivity of 86% and a specificity of 91%. In contrast, apolipoprotein E4 allele frequency and cerebrospinal fluid tau levels did not differ significantly between the two groups. In order to further dissect out neuropathological correlates of the dysfunctional occipital lobe, postmortem brains from 19 patients with AD and 17 with DLB as well as 11 brains from normal controls were examined. A distinct and extensive spongiform change with coexisting gliosis was variably noted throughout cerebral white matter with relative sparing of gray matter in DLB. Notably, the white matter spongiform change and gliosis was most prominently and consistently found in the occipital region of DLB, and the severity of the spongiform change in each brain region generally paralleled to the regional difference in reduced glucose metabolism between the living AD and DLB patients. These findings suggest that (1) among several potential antemortem biomarkers in the diagnosis of DLB, measures of the glucose metabolism in the occipital cortex may be an informative diagnostic aid to distinguish DLB from AD; and (2) a pathological process that generates widespread spongiform change and gliosis in long projection fibers may contribute, at least in part, to the characteristic imaging features of DLB.","Aged;Alleles;Alzheimer Disease/cerebrospinal fluid/diagnosis/genetics/metabolism/pathology;Apolipoprotein E4;Apolipoproteins E/genetics;Brain/ metabolism/ pathology;Diagnosis, Differential;Female;Fluorodeoxyglucose F18;Gene Frequency;Gliosis/diagnosis/pathology;Glucose/ metabolism;Humans;Immunohistochemistry;Lewy Bodies/metabolism/pathology;Lewy Body Disease/cerebrospinal fluid/diagnosis/genetics/ metabolism/ pathology;Male;Nerve Tissue Proteins/metabolism;Occipital Lobe/metabolism;Sensitivity and Specificity;Synucleins;Tomography, Emission-Computed;Ubiquitins/metabolism;Visual Cortex/metabolism;tau Proteins/cerebrospinal fluid","Higuchi, M.;Tashiro, M.;Arai, H.;Okamura, N.;Hara, S.;Higuchi, S.;Itoh, M.;Shin, R. W.;Trojanowski, J. Q.;Sasaki, H.",2000,Apr,10.1006/exnr.2000.7342,0,
3884,"(18)F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia","OBJECTIVE: Recently, we developed a benzofuran derivative for the imaging of beta-amyloid plaques, 5-(5-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2 -amine ((18)F-FPYBF-2) (Ono et al., J Med Chem 54:2971-9, 2011). The aim of this study was to assess the feasibility of (18)F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using (11)C-Pittsburgh Compound B ((11)C-PiB). METHODS: 61 healthy volunteers (age: 53.7 +/- 13.1 years old; 19 male and 42 female; age range 24-79) and 55 patients with suspected dementia [Alzheimer's Disease (AD); early AD: n = 19 and moderate stage AD: n = 8, other dementia: n = 9, mild cognitive impairment (MCI): n = 16, cognitively normal: n = 3] for first clinical study underwent static head PET/CT scan using (18) F (-) FPYBF-2 at 50-70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0-50 min at the same instant. 16 subjects (volunteers: n = 5, patients with dementia: n = 11) (age: 66.3 +/- 14.2 years old; 10 males and 6 females) were evaluated for comparative study (50-70 min after injection) using (18)F-FPYBF-2 and (11)C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for (11)C-PiB analysis using cerebellar cortex as control. RESULTS: Studies with healthy volunteers showed that (18)F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50-70 min was low and stable (1.066 +/- 0.069) basically independent from age or gender. In patients with AD, (18)F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288 +/- 0.134, moderate AD: 1.342 +/- 0.191) than those of volunteers and other dementia (1.018 +/- 0.057). In comparative study, the results of (18)F-FPYBF-2 PET/CT were comparable with those of (11)C-PiB, and the Mean Cortical Index ((18)F-FPYBF-2: 1.173 +/- 0.215; (11)C-PiB: 1.435 +/- 0.474) showed direct proportional relationship with each other (p < 0.0001). CONCLUSIONS: Our first clinical study suggest that (18)F-FPYBF-2 is a useful PET tracer for the evaluation of beta-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.",Alzheimer disease;Amyloid imaging;Healthy volunteers;Positron emission tomography,"Higashi, T.;Nishii, R.;Kagawa, S.;Kishibe, Y.;Takahashi, M.;Okina, T.;Suzuki, N.;Hasegawa, H.;Nagahama, Y.;Ishizu, K.;Oishi, N.;Kimura, H.;Watanabe, H.;Ono, M.;Saji, H.;Yamauchi, H.",2018,Jan 31,,0,
3885,Regions of interest computed by SVM wrapped method for Alzheimer's disease examination from segmented MRI,"Accurate identification of the most relevant brain regions linked to Alzheimer's disease (AD) is crucial in order to improve diagnosis techniques and to better understand this neurodegenerative process. For this purpose, statistical classification is suitable. In this work, a novel method based on support vector machine recursive feature elimination (SVM-RFE) is proposed to be applied on segmented brain MRI for detecting the most discriminant AD regions of interest (ROIs). The analyses are performed both on gray and white matter tissues, achieving up to 100% accuracy after classification and outperforming the results obtained by the standard t-test feature selection. The present method, applied on different subject sets, permits automatically determining high-resolution areas surrounding the hippocampal area without needing to divide the brain images according to any common template.",,"Hidalgo-Munoz, A. R.;Ramirez, J.;Gorriz, J. M.;Padilla, P.",2014,,10.3389/fnagi.2014.00020,0,
3886,The value of perfusion computed tomography in predicting clinically relevant vasospasm in patients with aneurysmal subarachnoid hemorrhage,"Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP's sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required. © 2012 Springer-Verlag Berlin Heidelberg.",adult;article;brain blood flow;brain blood volume;brain infarction;brain perfusion;brain vasospasm;clinical article;clinical evaluation;computer assisted tomography;controlled study;diagnostic test accuracy study;Doppler echography;false positive result;female;human;male;mental deterioration;outcome assessment;perfusion computed tomography;predictive value;priority journal;process optimization;quantitative analysis;receiver operating characteristic;risk assessment;risk factor;sensitivity analysis;sensitivity and specificity;subarachnoid hemorrhage;time to maximum plasma concentration,"Hickmann, A. K.;Langner, S.;Kirsch, M.;Baldauf, J.;Müller, C.;Khaw, A.;Schroeder, H. W. S.",2013,,,0,
3887,Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression--a longitudinal evaluation,"In a longitudinal evaluation of 37 patients with severe depression who had undergone brain magnetic resonance imaging (MRI) 6 months-2 years (mean 14.1 months) previously, the degree of residual dysfunction was predicted by the extent of subcortical white matter hyperintensities (WMHS, p < .01), longer time elapsed since the MRI scan (p < .05), older age (p < .05), and older age at onset of affective disorder (p < .05). Ten (27%) patients developed ""probable"" dementia syndromes of the vascular type, with such syndromes being predicted by WMHS (p < .01) and older age of onset of affective disorder (p < .05). Institutionalization of patients was predicted largely by the combination of chronic depression, progressive cognitive decline, and advanced age. The study supports the notion that a subgroup of patients with late-onset depressive disorders, without a family history of depression, and with risk factors to cerebrovascular disease, have extensive WMHS on MRI, and that such structural brain changes predispose to chronic depression and progressive cognitive decline.",Adult;Aged;Brain/ pathology;Depressive Disorder/ pathology/psychology;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Prognosis;Psychiatric Status Rating Scales;Treatment Outcome,"Hickie, I.;Scott, E.;Wilhelm, K.;Brodaty, H.",1997,Sep 1,10.1016/s0006-3223(96)00363-0,0,
3888,Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability,"There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n=201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a ""sham"" DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and K(Trans) estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible.",Blood-brain barrier;Cerebral small vessel disease;Dynamic contrast-enhanced MRI;Tracer kinetic modelling,"Heye, A. K.;Thrippleton, M. J.;Armitage, P. A.;Valdes Hernandez Mdel, C.;Makin, S. D.;Glatz, A.;Sakka, E.;Wardlaw, J. M.",2016,Jan 15,10.1016/j.neuroimage.2015.10.018,0,
3889,Increase in periventricular white matter hyperintensities parallels decline in mental processing speed in a non-demented elderly population,"OBJECTIVE: To investigate the influence of deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVWMH) on progression of cognitive decline in non-demented elderly people. METHODS: All data come from the nested MRI sub-study of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing. Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex, age, education, treatment group, and test version when applicable. RESULTS: We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed (p = 0.0075). In addition, we found that the progression in PVWMH volume paralleled the decline in mental processing speed (p = 0.024). In contrast, neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests. CONCLUSION: PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed.","Cerebral Infarction [diagnosis] [drug therapy] [pathology];Cerebral Ventricles [pathology];Cognition Disorders [diagnosis] [psychology];Dementia, Vascular [diagnosis] [drug therapy] [pathology];Disease Progression;Double-Blind Method;Hydroxymethylglutaryl-CoA Reductase Inhibitors [adverse effects] [therapeutic use];Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Neuropsychological Tests;Pravastatin [adverse effects] [therapeutic use];Prospective Studies;Reaction Time [physiology];Statistics as Topic;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-stroke","Heuvel, D. M.;Dam, V. H.;Craen, A. J.;Admiraal-Behloul, F.;Olofsen, H.;Bollen, E. L.;Jolles, J.;Murray, H. M.;Blauw, G. J.;Westendorp, R. G.;Buchem, M. A.",2006,,10.1136/jnnp.2005.070193,0,
3890,Separation of beta-amyloid binding and white matter uptake of (18)F-flutemetamol using spectral analysis,"The kinetic components of the beta-amyloid ligand (18)F-flutemetamol binding in grey and white matter were investigated through spectral analysis, and a method developed for creation of parametric images separating grey and white matter uptake. Tracer uptake in grey and white matter and cerebellar cortex was analyzed through spectral analysis in six subjects, with (n=4) or without (n=2) apparent beta-amyloid deposition, having undergone dynamic (18)F-flutemetamol scanning with arterial blood sampling. The spectra were divided into three components: slow, intermediate and fast basis function rates. The contribution of each of the components to total volume of distribution (VT) was assessed for different tissue types. The slow component dominated in white matter (average 90%), had a higher contribution to grey matter VT in subjects with beta-amyloid deposition (average 44%) than without (average 6%) and was absent in cerebellar cortex, attributing the slow component of (18)F-flutemetamol uptake in grey matter to beta-amyloid binding. Parametric images of voxel-based spectral analysis were created for VT, the slow component and images segmented based on the slow component contribution; confirming that grey matter and white matter uptake can be discriminated on voxel-level using a threshold for the contribution from the slow component to VT.",,"Heurling, K.;Buckley, C.;Vandenberghe, R.;Laere, K. V.;Lubberink, M.",2015,,,0,
3891,Shape and volume of lacunar infarcts: a 3D MRI study in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: The shape and exact size of lacunar infarcts have been investigated only postmortem. Recent imaging techniques based on triangulation and connectivity can now be used for 3D segmentation of cerebral lesions. The shape and size of lacunar infarcts was investigated using these techniques in 10 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients. METHODS: We segmented 102 lacunar infarcts on T1-weighted images. The surface of the corresponding set of voxels was computed as a mesh of triangles. Thereafter, the shape of each lesion in 3D was visually analyzed by 2 investigators. RESULTS: The volume of lesions ranged from 10.5 to 1146 mm, with 93% of them having a volume <500 mm; 83% lacunar infarcts had a spheroid or ovoid shape, but 17% presented as sticks, slabs, or with a complex shape. Lesions with multiple components appeared larger than the others, and a tail extension was noticed in 13 of 102 lesions. CONCLUSIONS: These results suggest the following: (1) most lacunar infarcts in CADASIL have a volume far below one third of that of a sphere of 15 mm in diameter, the upper limit currently used for their identification on 2D imaging; (2) a significant proportion of lacunar infarcts have a shape distinct from the spheroid-ovoid morphology; and (3) lesions with a complex shape may result from the involvement of the largest small arteries, confluence of ischemic lesions, or secondary tissue degeneration. The segmentation of lacunar infarcts appears promising to better understand the pathophysiology of tissue lesions secondary to small vessel diseases.","Aged;Arteries/pathology/ultrasonography;Brain/pathology;Brain Infarction/pathology;CADASIL/ diagnosis/genetics;Dementia, Vascular/diagnosis/ genetics/ pathology;Echo-Planar Imaging/ methods;Humans;Image Enhancement;Imaging, Three-Dimensional/ methods;Ischemia/pathology;Magnetic Resonance Imaging/ methods;Middle Aged;Models, Anatomic;Models, Statistical;Mutation;Neurodegenerative Diseases/pathology;Receptors, Notch/genetics","Herve, D.;Mangin, J. F.;Molko, N.;Bousser, M. G.;Chabriat, H.",2005,Nov,10.1161/01.str.0000185678.26296.38,0,
3892,Three-dimensional mri analysis of individual volume of lacunes in CADASIL,"BACKGROUND AND PURPOSE: Three-dimensional MRI segmentation may be useful to better understand the physiopathology of lacunar infarctions. Using this technique, the distribution of lacunar infarctions volumes has been recently reported in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Whether the volume of each lacune (individual lacunar volume [ILV]) is associated with the patients' other MRI lesions or vascular risk factors has never been investigated. The purpose of this study was to study the impact of age, vascular risk factors, and MRI markers on the ILV in a large cohort of patients with CADASIL. METHODS: Of 113 patients with CADASIL, 1568 lacunes were detected and ILV was estimated after automatic segmentation on 3-dimensional T1-weighted imaging. Relationships between ILV and age, blood pressure, cholesterol, diabetes, white matter hyperintensities load, number of cerebral microbleeds, apparent diffusion coefficient, brain parenchymal fraction, and mean and median of distribution of lacunes volumes at the patient level were investigated. We used random effect models to take into account intraindividual correlations. RESULTS: The ILV varied from 4.28 to 1619 mm. ILV was not significantly correlated with age, vascular risk factors, or different MRI markers (white matter hyperintensity volume, cerebral microbleed number, mean apparent diffusion coefficient or brain parenchymal fraction). In contrast, ILV was positively correlated with the patients' mean and median of lacunar volume distribution (P≤0.0001). CONCLUSIONS: These results suggest that the ILV is not related to the associated cerebral lesions or to vascular risk factors in CADASIL, but that an individual predisposition may explain predominating small or predominating large lacunes among patients. Local anatomic factors or genetic factors may be involved in these variations. Copyright © 2009 American Heart Association. All rights reserved.",,"Hervé, D.;Godin, O.;Dufouil, C.;Viswanathan, A.;Jouvent, E.;Pachaí, C.;Guichard, J. P.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2009,1,,0,
3893,Cadasil,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a dominantly inherited small artery disease that leads to dementia and disability in mid-life. The clinical presentation of CADASIL is variable between and within affected families and is characterized by symptoms including migraine with aura, subcortical ischemic events, mood disturbances, apathy, and cognitive impairment. The mean age at onset of symptoms is 45 years, with variable duration of the disease ranging from 10 to 40 years. In 1996, linkage studies mapped and identified mutations in the NOTCH3 gene on chromosome 19 as causative in CADASIL. Head magnetic resonance imaging (MRI) is always abnormal in participants with NOTCH3 mutations after age 35. Magnetic resonance imaging shows on T2-weighted images or fluid attenuation inversion recovery (FLAIR) sequence, widespread areas of increased signal in the white matter associated with focal hyperintensities in basal ganglia, thalamus, and brainstem. The pathologic hallmark of CADASIL is the presence of electron-dense granules in the media of arterioles that can be identified by electron microscopic evaluation of skin biopsies. © 2010 The Author(s).",,"Hervé, D.;Chabriat, H.",2010,December,,0,
3894,Natural history of the vascular dementias: A prospective study of seven cases,"The clinical course of vascular dementia has been described as a stepwise deterioration over time. We studied the chronologic course of cognitive performance over 1-4 years in seven patients with known ischemic cerebrovascular disease whose dementia subtype was assigned according to the clinical history and the pattern of white matter lesions seen on magnetic resonance imagine (MRI). One patient had the lacunar state, three had subcortical arteriosclerotic encephalopathy and three had multiple cortical and subcortical strokes. All were being treated with an antiplatelet agent and six received antihypertensive therapy. Four of the seven vascular dementia patients improved cognitively over the first year. A fluctuating course was eventually seen in all patients. None showed stepwise deterioration of cognitive function over time. The MRI was useful in subclassifying vascular dementia patients, but the clinical course did not appear to vary as a function of the dementia subtype.",brain ischemia;central nervous system;cerebrovascular disease;clinical article;cognition;computer analysis;dementia;diagnosis;etiology;human;nuclear magnetic resonance imaging;peripheral vascular system;priority journal;psychological aspect,"Hershey, L. A.;Modic, M. T.;Jaffe, D. F.;Greenough, P. G.",1986,,,0,
3895,Magnetic resonance imaging in vascular dementia,"Patients with vascular dementia show distinctive white matter lesions on MRI. We performed MRI on 34 patients with documented ischemic cerebrovascular disease to see whether demented and nondemented patients differ with respect to enlarged CSF spaces or white matter lesions. All eight demented patients had white matter lesions on MRI, just as did many borderline and nondemented patients. Enlargement of central CSF spaces was the only radiographic feature that was seen more commonly in demented than in nondemented patients with ischemic cerebrovascular disease.","Aged;Aged, 80 and over;Brain/ pathology/radiography;Cerebrovascular Disorders/complications/ pathology;Dementia/etiology/ pathology;Female;Humans;Ischemic Attack, Transient/pathology;Magnetic Resonance Spectroscopy;Male;Middle Aged","Hershey, L. A.;Modic, M. T.;Greenough, P. G.;Jaffe, D. F.",1987,Jan,,0,
3896,CSF biomarkers and neuropsychological profiles in patients with cerebral small-vessel disease,"Despite existing criteria, differential diagnosis of Vascular Dementia (VD) and Alzheimer's disease (AD) remains difficult. The aim of this study is to figure out cognitive and biomarker profiles that may help to distinguish between VD, AD and AD + Cerebral Small Vessel Disease (CSVD). We examined a cohort of patients with CSVD (n = 92). After stratification of cognitive impaired patients (n = 59) using the standard CSF beta-amyloid 42/40 ratio cut-off point of 0.975, we obtained two groups which differed with respect to several features: 32 patients with normal beta-amyloid 42/40 ratio (>0.975) showed markedly impaired blood-brain-barrier function as indicated by an elevated albumin ratio (median 8.35). They also differed in cognitive profiles when compared to 27 patients with AD typical beta-amyloid ratio and normal albumin ratio. We also enrolled an additional group of patients with AD (no significant CSVD on MRI, n = 27) which showed no impairment of the blood-brain-barrier. We showed a negative correlation between the albumin ratio and executive cognitive function (p = 0.016) and a negative correlation between memory function and typical AD markers like Tau (p = 0.004) and p181-Tau (p = 0.023) in our cohort. We suppose that the group of patients with normal beta-amyloid ratio represents VD while patients in the other groups represent AD+CSVD and pure AD. Our results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions. © 2014 Hermann et al.",albumin;amyloid beta protein;biological marker;phosphoprotein;tau protein;adult;aged;Alzheimer disease;article;blood brain barrier;case control study;cerebrospinal fluid analysis;cerebrovascular disease;cognitive defect;cohort analysis;controlled study;disease severity;executive function;female;human;major clinical study;male;memory;mental deterioration;multiinfarct dementia;neuropsychology;white matter lesion,"Hermann, P.;Romero, C.;Schmidt, C.;Reis, C.;Zerr, I.",2014,,,0,
3897,"Cognitive impairment in chronic kidney disease: Clinical manifestation, pathomechanisms and therapeutic consequences","In view of the high prevalence, cognitive abnormalities have a direct relevance in patients with chronic kidney disease. Characterized by cognitive slowing, attention deficits, disturbances in the planning, initiation and implementation of actions as well as language and memory deficits, cognitive impairment in patients with chronic kidney disease is mostly the consequence of subcortical arteriosclerotic encephalopathy. Subcortical arteriosclerotic encephalopathy usually results from systemic microangiopathy, which in the brain is most strongly manifested in the white matter. In magnetic resonance imaging, hyperintensities in T2-weighted images can be detected. Therapeutic approaches involve the treatment of chronic kidney disease, management of joint risk factors of chronic kidney disease and subcortical arteriosclerotic encephalopathy and the prescription of anti-dementia drugs for patients with the clinical symptoms of dementia. © 2013 Springer-Verlag Berlin Heidelberg.",,"Hermann, D. M.;Grotz, W.",2013,July,,0,
3898,Multiple microbleeds are related to cerebral network disruptions in patients with early Alzheimer's disease,"Background: Cerebral microbleeds are a manifestation of small vessel disease and are common in patients with Alzheimer's disease (AD). However, their clinical significance in this condition is uncertain. We hypothesized that microbleeds contribute to disturbances of the cerebral network in AD and as such may affect cognition. Objective: The goal of this study was to examine the relationship between microbleeds and brain networks in patients with amnestic mild cognitive impairment (aMCI) or early AD. Methods: Sixty-seven patients (77.9 ± 7.5 years) with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph theoretical analysis were used to reconstruct brain networks and to quantify network efficiency for each patient. Network measures were compared between patients without and with ≥1 microbleeds and between patients without or with ≥3 microbleeds. In secondary analyses, cognitive functioning was compared between groups. Analyses were adjusted for age and gender, and additionally for other markers of small vessel disease and atrophy. Results: Network measures did not differ between patients with ≥1 microbleed (n = 26) and patients without microbleeds (n = 41). However, patients with ≥3 microbleeds (n = 11) showed significant white matter disruptions, longer path length, and less global efficiency than patients without microbleeds, independent of other markers of small vessel disease and atrophy. Cognitive functioning did not differ between patients without microbleeds and patients with ≥1 or ≥3 microbleeds. Conclusion: Multiple microbleeds are related to structural network disruption in patients with early AD, but their direct impact on cognitive functioning appears to be limited. © 2014 A IOS Press and the authors. All rights reserved.",,"Heringa, S. M.;Reijmer, Y. D.;Leemans, A.;Koek, H. L.;Kappelle, L. J.;Biessels, G. J.",2014,2014,,0,
3899,Diagnostic imaging of dementia in the elderly,"Dementia is a frequent problem in elderly patients. More than age per se, it may influence the indication for invasive diagnostic and therapeutic procedures to treat other diseases. Here, the role of tomographic imaging methods for differential diagnosis of dementia will be reviewed briefly, with the new possibilities that became available recently. Computed tomography (CT) of the brain is used primarily to detect potentially treatable conditions, such as multiple ischemic infarcts, hematomas, hydrocephalus and brain tumors. It should be performed even at higher age if the general condition of the patient is good enough not to exclude all specific therapeutic measures. Magnetic resonance imaging (MRI) is more sensitive for ischemic white matter lesions and hippocampal atrophy and should therefore used preferentially in mildly affected patients. Functional imaging methods, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), are necessary only in clinically unclear cases to demonstrate functional impairment of association cortex.",,"Herholz, K.",1997,Jul-Aug,,0,
3900,A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients,"Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia.","Adolescent;Adult;Aged;Brain/*pathology;Brain Neoplasms/*complications/*pathology;Cognition;Cohort Studies;Emotions;*Empathy;Female;Glioma/*complications/*pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology;Personality Disorders/*etiology;Regression Analysis;Social Behavior;Young Adult;Cingulum;Empathy;Inferior fronto-occipital fasciculus;Low-grade glioma;Social cognition;Uncinate fasciculus","Herbet, G.;Lafargue, G.;Moritz-Gasser, S.;Menjot de Champfleur, N.;Costi, E.;Bonnetblanc, F.;Duffau, H.",2015,Apr,10.1016/j.neuropsychologia.2015.02.015,0,
3901,Atypical brain lymphoma revealed by ocular abnormalities: A case report,"A 72 year-old woman is hospitalized and explored in the neurological department because of dementia discovered after a vitrectomy performed to treat a relapsing chronic uveitis. MRI examination shows atypical hyperintense white matter lesions on T2 weighted images related to Lyme disease. Worsening of clinical status, despite appropriate medical treatment and apparition of enhanced nodules MR images rules out the diagnosis of lyme disease and is attribuated to brain metastases. The seach for primitive tumor is not contributive and a brain biopsy is performed. It discloses a B cells non-hodgkin lymphoma. This case report stresses two points: First, a lymphoma must be one of the diagnosis to evocate if imaging shows an enhancing nodule, or extensive hypersignal of the white matter, second: It emphasizes the value of vitreous analysis searching for lymphoma during chronic uveitis associated to neurological symptoms.",,"Héran, F.;Lafitte, F.;Berroir, S.;Blustajn, J.;Parrat, E.",2001,2001,,0,
3902,White matter hyperintensities and cognitive dysfunction in alzheimer disease,"The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P <.01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.",,"Heo, J. H.;Lee, S. T.;Chu, K.;Park, H. J.;Shim, J. Y.;Kim, M.",2009,September,,0,
3903,[Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia] Quantifizierung mikroangiopathischer Hirnparenchymlasionen zur Abgrenzung altersnormaler gegenuber pathologischer Auspragung bei Altersdemenzen,"PURPOSE: To quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. MATERIALS AND METHODS: In a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. RESULTS: The WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. CONCLUSION: A rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Brain/blood supply/ pathology;Confidence Intervals;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Psychological Tests;Psychometrics","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.;Frolich, F.",2005,Jun,,0,
3904,[Quantification of microangiopathic lesions in brain parenchyma and age-adjusted mean scores for the diagnostic separation of normal from pathological values in senile dementia],"PURPOSE: To quantify microangiopathic lesions in the cerebral white matter and to develop age-corrected cut-off values for separating normal from dementia-related pathological lesions. MATERIALS AND METHODS: In a memory clinic, 338 patients were investigated neuropsychiatrically by a psychological test battery and by MRI. Using a FLAIR sequence and a newly developed rating scale, white matter lesions (WMLs) were quantified with respect to localization, number and intensity, and these ratings were condensed into a score. The WML scores were correlated with the mini-mental state examination (MMSE) and clinical dementia rating (CDR) score in dementia patients. A non-linear smoothing procedure was used to calculate age-related mean values and confidence intervals, separate for cognitively intact subjects and dementia patients. RESULTS: The WML scores correlated highly significantly with age in cognitively intact subjects and with psychometric scores in dementia patients. Age-adjusted WML scores of cognitively intact subjects were significantly different from those of dementia patients with respect to the whole brain as well as to the frontal lobe. Mean value and confidence intervals adjusted for age significantly separated dementia patients from cognitively intact subjects over an age range of 54 through 84 years. CONCLUSION: A rating scale for the quantification of WML was validated and age-adjusted mean values with their confidence intervals for a diagnostically relevant age range were developed. This allows an easy to handle, fast and reliable diagnosis of the vascular component in senile dementia.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/pathology;Brain/blood supply/*pathology;Confidence Intervals;Diagnosis, Differential;Female;Humans;*Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Psychological Tests;Psychometrics","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.;Frolich, F.",2005,Jun,10.1055/s-2005-858193,0,
3905,[Does magnetization transfer ratio (MTR) contribute to the diagnosis and differential diagnosis of the dementias?] Leistet die Magnetization-Transfer-Ratio (MTR) einen Beitrag zur Diagnostik und Differenzialdiagnostik der Demenzen?,"PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging procedure aiming at the quantification of the structural integrity of brain tissue. Its contribution to the differential diagnosis of dementias was examined and discussed in relation to the pathogenesis of age-related dementias. MATERIALS AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general physical and neuropsychiatric examination, and underwent neuropsychologic testing and neuroimaging using MRI. Their clinical diagnoses were based on standard operational research criteria. Additionally, the MTR in 10 defined regions of interest (ROI) was determined. This investigation was performed using a T1-weighted SE sequence. Average MTR values were determined in the individual ROI and their combinations and correlated with the age, gender, cognitive impairment and clinical diagnosis. Sensitivity, specificity, positive and negative predictive value were determined, as well as the rate of correct classifications. RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly, though significantly, with age in the hippocampus and with gender in the dorsal corpus callosum. In contrast, the MTR in the frontal white matter correlates strongly and highly significantly with cognitive impairment in patients with dementia. The differential diagnostic assignment of Alzheimer's disease versus vascular dementia by MTR provides a correct classification of approximately 50 % to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs. Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs. Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate functional changes in the brain tissue between cognitive healthy and demented patients, and correlate with the cognitive loss, but not with age and gender. In principle, the MTR is suitable for the diagnosis of age-related dementias, but does not contribute substantially to the differential diagnosis of vascular dementia vs. Alzheimer's disease. The present results support the assumption of a synergy between vascular and degenerative components of age-related dementias.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;Brain/ pathology;Dementia/ diagnosis/pathology;Dementia, Vascular/diagnosis/pathology;Diagnosis, Differential;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neuropsychological Tests;Psychometrics;Sensitivity and Specificity;Sex Factors","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.",2004,Dec,,0,
3906,[Does magnetization transfer ratio (MTR) contribute to the diagnosis and differential diagnosis of the dementias?],"PURPOSE: The magnetization transfer ratio (MTR) is a MR-based neuroimaging procedure aiming at the quantification of the structural integrity of brain tissue. Its contribution to the differential diagnosis of dementias was examined and discussed in relation to the pathogenesis of age-related dementias. MATERIALS AND METHODS: Sixty-one patients from a memory clinic were diagnosed by general physical and neuropsychiatric examination, and underwent neuropsychologic testing and neuroimaging using MRI. Their clinical diagnoses were based on standard operational research criteria. Additionally, the MTR in 10 defined regions of interest (ROI) was determined. This investigation was performed using a T1-weighted SE sequence. Average MTR values were determined in the individual ROI and their combinations and correlated with the age, gender, cognitive impairment and clinical diagnosis. Sensitivity, specificity, positive and negative predictive value were determined, as well as the rate of correct classifications. RESULTS: For cognitive healthy subjects, the MRT values correlate only mildly, though significantly, with age in the hippocampus and with gender in the dorsal corpus callosum. In contrast, the MTR in the frontal white matter correlates strongly and highly significantly with cognitive impairment in patients with dementia. The differential diagnostic assignment of Alzheimer's disease versus vascular dementia by MTR provides a correct classification of approximately 50 % to 70 %. PPV for no dementia vs. vascular dementia or the NPV for vascular vs. Alzheimer's disease are considerably higher exceeding 80 %. For no dementia vs. Alzheimer's disease, the NPV was over 90 %. CONCLUSION: MTR values indicate functional changes in the brain tissue between cognitive healthy and demented patients, and correlate with the cognitive loss, but not with age and gender. In principle, the MTR is suitable for the diagnosis of age-related dementias, but does not contribute substantially to the differential diagnosis of vascular dementia vs. Alzheimer's disease. The present results support the assumption of a synergy between vascular and degenerative components of age-related dementias.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;Brain/*pathology;Dementia/*diagnosis/pathology;Dementia, Vascular/diagnosis/pathology;Diagnosis, Differential;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Neuropsychological Tests;Psychometrics;Sensitivity and Specificity;Sex Factors","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.",2004,Dec,10.1055/s-2004-813650,0,
3907,[Microangiopathic lesions of white matter. Quantitation of cerebral MRI findings and correlation with psychological tests] Mikroangiopathische Lasionen der weissen Hirnsubstanz. Quantifizierung im MRT und Korrelation mit psychologischen Testergebnissen,"AIM: The importance of vascular lesions in the white matter of the brain (WML) is viewed differently. Diagnostic evaluation is determined by experience and age-associated normal values are not available. MATERIAL AND METHODS: One hundred fifty-two patients aged 68.8 years (range 50-89) were examined at a memory clinic using a magnetic resonance FLAIR sequence,which is sensitive for WML. The WMLs were entered with respect to size, localization, laterality, and density. The WML scores of 76 clinically and psychologically normal subjects with microangiopathic lesions and 27 patients with vascular dementia were correlated with psychological test results. The contribution of local WML scores to the differentiation between age-associated microangiopathy and vascular dementia was calculated using logistic regression analysis. Nonparametric monotonic regression was used to analyse the age-associated WML scores of both groups, taking individual age into account. RESULTS: The WML scores correlated linearly with the age of psychologically normal subjects but with degree of dementia for those with vascular dementia, and it allowed differentiation between these two groups with an accuracy of up to 88% and specificity of approximately 95% with reference to the right frontal region. The odds ratios of the general and frontal WML scores were significantly different (1,102 and 1,400, respectively). Statistical significance of the age-associated WML scores varied for different age ranges. CONCLUSION: It is possible to differentiate psychologically normal subjects with microangiopathic brain lesions from patients with vascular dementia on MRI when referring to frontal WML scores.","Aged;Aged, 80 and over;Amygdala/pathology;Brain Ischemia/ diagnosis/psychology;Cerebral Cortex/pathology;Cerebral Infarction/ diagnosis/psychology;Dementia, Vascular/ diagnosis/psychology;Diagnosis, Differential;Female;Hippocampus/pathology;Humans;Image Enhancement;Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Middle Aged;Neuropsychological Tests/statistics & numerical data;Psychometrics;Sensitivity and Specificity","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.",2003,Apr,,0,
3908,[Microangiopathic lesions of white matter. Quantitation of cerebral MRI findings and correlation with psychological tests],"AIM: The importance of vascular lesions in the white matter of the brain (WML) is viewed differently. Diagnostic evaluation is determined by experience and age-associated normal values are not available. MATERIAL AND METHODS: One hundred fifty-two patients aged 68.8 years (range 50-89) were examined at a memory clinic using a magnetic resonance FLAIR sequence,which is sensitive for WML. The WMLs were entered with respect to size, localization, laterality, and density. The WML scores of 76 clinically and psychologically normal subjects with microangiopathic lesions and 27 patients with vascular dementia were correlated with psychological test results. The contribution of local WML scores to the differentiation between age-associated microangiopathy and vascular dementia was calculated using logistic regression analysis. Nonparametric monotonic regression was used to analyse the age-associated WML scores of both groups, taking individual age into account. RESULTS: The WML scores correlated linearly with the age of psychologically normal subjects but with degree of dementia for those with vascular dementia, and it allowed differentiation between these two groups with an accuracy of up to 88% and specificity of approximately 95% with reference to the right frontal region. The odds ratios of the general and frontal WML scores were significantly different (1,102 and 1,400, respectively). Statistical significance of the age-associated WML scores varied for different age ranges. CONCLUSION: It is possible to differentiate psychologically normal subjects with microangiopathic brain lesions from patients with vascular dementia on MRI when referring to frontal WML scores.","Aged;Aged, 80 and over;Amygdala/pathology;Brain Ischemia/*diagnosis/psychology;Cerebral Cortex/pathology;Cerebral Infarction/*diagnosis/psychology;Dementia, Vascular/*diagnosis/psychology;Diagnosis, Differential;Female;Hippocampus/pathology;Humans;*Image Enhancement;*Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Middle Aged;*Neuropsychological Tests/statistics & numerical data;Psychometrics;Sensitivity and Specificity","Hentschel, F.;Kreis, M.;Damian, M.;Krumm, B.",2003,Apr,10.1007/s00115-003-1488-3,0,
3909,Reliability of quantifying vascular white matter brain lesions - A contribution to reproducible quantitative diagnosis,"Purpose: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The ""experience- based"" evaluation is insufficient. Rating scales may contribute to reproducible quantification. Materials and Methods: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). Results: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. Conclusion: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.",adult;article;brain injury;brain tissue;clinical article;controlled study;correlation analysis;diagnostic accuracy;human;microangiopathy;multiinfarct dementia;neuroimaging;nuclear magnetic resonance imaging;observer variation;priority journal;quantitative analysis;rating scale;reliability;reproducibility;scoring system;surgical anatomy;vascular subcortical dementia;vascular white matter brain lesion,"Hentschel, F.;Kreis, M.;Damian, M.;Diepers, M.;Disqué, C.;Dzialowski, I.;Kitzler, H.;Rodewald, A.;Struffert, T.;Trittmacher, S.;Wille, P. R.;Krumm, B.",2005,,,0,
3910,[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis] Reliabilitat der Quantifizierung von vaskularen Lasionen der weissen Hirnsubstanz -- ein Beitrag zur replizierbaren quantitativen Diagnostik,"PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The ""experience-based"" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.","Aged;Brain/ pathology;Data Interpretation, Statistical;Dementia, Vascular/ diagnosis/pathology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Observer Variation;Time Factors","Hentschel, F.;Kreis, M.;Damian, M.;Diepers, M.;Disque, C.;Dzialowski, I.;Kitzler, H.;Rodewald, A.;Struffert, T.;Trittmacher, S.;Wille, P. R.;Krumm, B.",2005,Jan,,0,
3911,[Reliability of quantifying vascular white matter brain lesions -- a contribution to reproducible quantitative diagnosis],"PURPOSE: Microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The ""experience-based"" evaluation is insufficient. Rating scales may contribute to reproducible quantification. MATERIALS AND METHODS: In MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). RESULTS: As to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. CONCLUSION: The rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age-associated physiological vs. pathological size of the WML can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics.","Aged;Brain/*pathology;Data Interpretation, Statistical;Dementia, Vascular/*diagnosis/pathology;Diagnosis, Differential;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Observer Variation;Time Factors","Hentschel, F.;Kreis, M.;Damian, M.;Diepers, M.;Disque, C.;Dzialowski, I.;Kitzler, H.;Rodewald, A.;Struffert, T.;Trittmacher, S.;Wille, P. R.;Krumm, B.",2005,Jan,10.1055/s-2004-813858,0,
3912,White matter lesions - age-adjusted values for cognitively healthy and demented subjects,"OBJECTIVES: To develop age-adjusted norms for white matter lesions (WML) and to differentiate dementia from mild cognitive impairment and normal aging. MATERIALS AND METHODS: 240 patients underwent a comprehensive clinical, neuropsychological and MRI examination. A scale was developed quantify WML in anatomically defined regions by rating size and frequency. FLAIR sequences were used to determine a global and a frontal score. The scores were correlated with the psychometric test results and the final clinical diagnosis: cognitively normal (CN), mild cognitive impairment (MCI), Alzheimer's Disease (AD), vascular dementia (VD). Age-adjusted curves for WML scores were calculated by means of a non-parametic smoothing method. RESULTS: WML scores of the whole cerebrum and the frontal lobe were significantly increased in vascular dementia as compared to CN, MCI and AD. Individual WML scores correlated significantly with age and neuropsychological test results. For the age range 55-72, the WML scores of VD were significantly different from those of CN, MCI and AD. CONCLUSIONS: Age-corrected WML load was significantly higher in vascular dementia as compared to MCI, AD and cognitively normals over a wide age range.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Brain/*pathology;Case-Control Studies;Cognition Disorders/*pathology;Dementia, Vascular/*pathology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Hentschel, F.;Damian, M.;Krumm, B.;Froelich, L.",2007,Mar,10.1111/j.1600-0404.2006.00762.x,0,
3913,Morphometry of the corpus callosum in patients with questionable and mild dementia,"Previous studies have shown a reduction in corpus callosum area in advanced Alzheimer's disease, but it is unclear whether callosal atrophy is present in the transitional phase between health and the onset of dementia. The aim of this study was to investigate whether callosal atrophy is present in subjects with questionable and mild dementia and to assess the diagnostic value of callosal measures. In 83 subjects aged 72 to 85 years (33 normal controls, 27 patients with questionable dementia, 23 with mild Alzheimer's disease), magnetic resonance images were recorded and the mid-sagittal callosal area measured. Significant differences were found between normal controls and mild dementia. In subjects with questionable dementia callosal size was intermediate between normal controls and mild Alzheimer's disease. However, callosal measures were unsuitable for diagnostic differentiation between healthy subjects, subjects with questionable dementia, and subjects with mild Alzheimer's disease. The severity of white matter changes did not differ between the groups.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Analysis of Variance;Atrophy;Case-Control Studies;Corpus Callosum/ pathology;Dementia/ pathology;Diagnosis, Differential;Female;Humans;Male;Predictive Value of Tests;Severity of Illness Index","Hensel, A.;Wolf, H.;Kruggel, F.;Riedel-Heller, S. G.;Nikolaus, C.;Arendt, T.;Gertz, H. J.",2002,Jul,,0,
3914,Association between global brain volume and the rate of cognitive change in elderly humans without dementia,"Patients with mild cognitive deficits experience different types of evolution. They are at increased risk of developing dementia, but they have also a chance of remaining stable in cognition or of improving. We investigated whether global brain volume, callosal size and hippocampal size are associated with the rate of cognitive change in elderly without dementia. Volumetric MR images were recorded from 39 controls and 35 patients with questionable dementia who were followed up longitudinally for a mean of 2.3 years. The outcome measure was the annual change in the test score in the Structured Interview for the Diagnosis of Alzheimer's Dementia and Multi-Infarct Dementia, which includes all items of the Mini-Mental State Examination. Global brain volume, grey matter volume and white matter volume were the only significant independent predictors of the rate of cognitive change.","Aged;Aged, 80 and over;Brain/ anatomy & histology/ physiopathology;Cognition Disorders/ diagnosis/ physiopathology;Corpus Callosum/anatomy & histology/physiopathology;Female;Follow-Up Studies;Hippocampus/anatomy & histology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Severity of Illness Index","Hensel, A.;Wolf, H.;Busse, A.;Arendt, T.;Gertz, H. J.",2005,,10.1159/000083501,0,
3915,Age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI,"Our purpose was to investigate leukoaraiosis (LA) using three-dimensional MR imaging combined with advanced image-processing technology to attempt to group signal abnormalities according to their etiology. Coronal T2-weighted fast fluid-attenuated inversion-recovery (FLAIR) sequences and three-dimensional T1-weighted fast spoiled gradient recalled echo sequences were used to examine cerebral white matter changes in 75 elderly people with memory complaint but no dementia. They were otherwise healthy, community-dwelling subjects. Three subtypes of LA were defined on the basis of their shape, geography and extent: the so-called subependymal/subpial LA, perivascular LA and ""bands"" along long white matter tracts. Subependymal changes were directly contiguous with ventricular spaces. They showed features of ""water hammer"" lesions with ventricular systematisation and a more frequent location around the frontal horns than around the bodies (P=.0008). The use of cerebrospinal fluid (CSF) contiguity criterion allowed a classification of splenial changes in the subpial group. Conversely, posterior periventricular lesions in the centrum ovale as well as irregular and extensive periventricular lesions were not directly contiguous with CSF spaces. The so-called perivascular changes showed features of small-vessel-associated disease; they surrounded linear CSF-like signals that followed the direction of perforating vessels. Distribution of these perivascular changes appeared heterogeneous (P ranging from .04 to 5.10(-16)). These findings suggest that subependymal/subpial LA and subcortical LA may be separate manifestations of a single underlying pulse-wave encephalopathy.","Aged;Aged, 80 and over;Aging/ physiology;Chi-Square Distribution;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Leukoaraiosis/ pathology;Magnetic Resonance Imaging/ methods;Memory Disorders/ pathology;Middle Aged","Henry Feugeas, M. C.;De Marco, G.;Peretti, II;Godon-Hardy, S.;Fredy, D.;Claeys, E. S.",2005,Nov,10.1016/j.mri.2005.09.002,0,
3916,Medial temporal lobe atrophy in stroke patients: relation to pre-existing dementia,"OBJECTIVE: The links between stroke and Alzheimer's disease seem to be closer than expected by chance. In a previous study it was shown that up to 16% of patients admitted for stroke had pre-existing dementia. Medial temporal lobe atrophy (MTLA) is strongly associated with Alzheimer's disease. The aim of this study was to determine the prevalence of MTLA and its relation with pre-existing dementia. METHOD: The study was conducted on 170 consecutive stroke patients (87 women; median age 75 years; 152 infarcts), who underwent non-contrast CT with temporal lobe oriented 2 mm contiguous slices at admission. A cut off point of 11.5 mm was used to differentiate patients with and without MTLA. Pre-existing dementia was assessed using the informant questionnaire on cognitive decline in the elderly (IQCODE) with a cut off score of 104. RESULTS: Ninety four patients (55.3%) had MTLA, of whom 23 (24.5%) had pre-existing dementia; of 76 patients without MTLA, only four (5.3%) had pre-existing dementia (p=0.0007). The logistic regression analysis with MTLA as dependent variable found the following independent variables: increasing age (p<0.05), and global cerebral atrophy scores (p<0.01). The IQCODE scores just reached significance (p=0.05). CONCLUSION: Stroke patients with MTLA are more likely to have pre-existing dementia; this suggests that Alzheimer's disease might contribute to the dementia syndrome. A longitudinal follow up is now necessary to determine whether stroke patients with MTLA and without pre-existing dementia are at increased risk of Alzheimer's disease over subsequent years.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*psychology;Atrophy/pathology;Cerebrovascular Disorders/*diagnosis;Female;Humans;Male;Middle Aged;Psychiatric Status Rating Scales;Retrospective Studies;Surveys and Questionnaires;Temporal Lobe/*pathology;Time Factors","Henon, H.;Pasquier, F.;Durieu, I.;Pruvo, J. P.;Leys, D.",1998,Nov,,0,
3917,Are gait disturbances and white matter degeneration early indicators of vascular dementia?,"The objective of this study was to correlate clinical and brain imaging findings with walking inabilities in patients with possible vascular dementia. For 24 patients with suspected initial vascular dementia according to DSM-III-R, structured neurological, neuropsychological and neuroimaging (magnetic resonance tomography) examinations were evaluated alongside computerized gait analysis. All patients revealed an increased variability of gait lines of various degrees: mild (11%), moderate (32%) and severe (57%). Lateralization of gait patterns was present in 68% and bipedal instabilities of posture in 54%. These findings were significantly correlated with frontal periventricular white matter lesions (WMLs), which probably affect the thalamo-cortico-mediocapsular pathways. The association of gait abnormalities with WMLs of the frontocentral subcortical and periventricular territories in patients with possible vascular dementing illnesses may be used as an early indicator of the disease for follow-up and treatment trials. However, since the degree of gait impairment varies considerably relative to the common mild intellectual limitations, these structural lesions are unlikely to be directly related to the dementing process.","Aged;Aged, 80 and over;Brain/ pathology;Cerebrovascular Disorders/diagnosis/pathology/ultrasonography;Dementia, Vascular/ diagnosis/ pathology/ultrasonography;Echoencephalography;Female;Follow-Up Studies;Gait;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Degeneration;Prospective Studies;Psychiatric Status Rating Scales;Risk Factors","Hennerici, M. G.;Oster, M.;Cohen, S.;Schwartz, A.;Motsch, L.;Daffertshofer, M.",1994,May-Aug,,0,
3918,MRI biomarkers of vascular damage and atrophy predicting mortality in a memory clinic population,"Background and Purpose-MRI biomarkers play an important role in the diagnostic work-up of dementia, but their prognostic value is less well-understood. We investigated if simple MRI rating scales predict mortality in a memory clinic population. Methods-We included 1138 consecutive patients attending our memory clinic. Diagnostic categories were:subjective complaints (n=220), mild cognitive impairment (n=160), Alzheimer disease (n = 357), vascular dementia (n=46), other dementia (n = 136), and other diagnosis (n = 219). Baseline MRIs were assessed using visual rating scales for medial temporal lobe atrophy (range, 0-4), global cortical atrophy (range, 0-3), and white matter hyperintensities (range, 0-3). Number of microbleeds and presence of infarcts were recorded. Cox-regression models were used to calculate the risk of mortality. Results-Mean follow-up duration was 2.6 (±1.9) years. In unadjusted models, all MRI markers except infarcts predicted mortality. After adjustment for age, sex, and diagnosis, white matter hyperintensities, and microbleeds predicted mortality (white matter hyperintensities:hazard ratio [HR], 1.2;95% CI, 1.0-1.4;microbleeds:HR, 1.02 95% CI, 1.00-1.03;categorized:HR, 1.5;95% CI, 1.1-2.0). The predictive effect of global cortical atrophy was restricted to younger subjects (HR, 1.7;95% CI, 1.2-2.6). An interaction between microbleeds and global cortical atrophy indicated that mortality was especially high in patients with both microbleeds and global cortical atrophy. Conclusion-Simple MRI biomarkers, in addition to their diagnostic use, have a prognostic value with respect to mortality in a memory clinic population. Microbleeds were the strongest predictor of mortality. © 2009 American Heart Association, Inc.",age;aged;Alzheimer disease;article;blood vessel injury;brain atrophy;brain infarction;calculation;cognitive defect;confidence interval;controlled study;dementia;diagnostic procedure;female;follow up;global cortical atrophy;hazard ratio;human;major clinical study;male;mortality;multiinfarct dementia;nuclear magnetic resonance imaging;prediction;priority journal;prognosis;proportional hazards model;risk assessment;sex;temporal lobe;temporal lobe atrophy;vision;white matter,"Henneman, W. J. P.;Sluimer, J. D.;Cordonnier, C.;Baak, M. M. E.;Scheltens, P.;Barkhof, F.;Van Der Flier, W. M.",2009,,,0,
3919,Baseline CSF p-tau levels independently predict progression of hippocampal atrophy in Alzheimer disease,"OBJECTIVE: To investigate whether baseline CSF biomarkers are associated with hippocampal atrophy rate as a measure of disease progression in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls, controlling for baseline neuropsychological and MRI findings. METHODS: We assessed data from 31 patients with AD, 25 patients with MCI, and 19 controls (mean age 68 +/- 8 years; 39 [52%] female) who visited our memory clinic and had received serial MRI scanning (scan interval 1.7 +/- 0.7 years). At baseline, CSF biomarkers (amyloid beta 1-42, tau, and tau phosphorylated at threonine 181 [p-tau]) were obtained, as well as neuropsychological data. Baseline MRI scans were assessed using visual rating scales for medial temporal lobe atrophy (MTA), global cortical atrophy, and white matter hyperintensities. Hippocampal atrophy rates were estimated using regional nonlinear ""fluid"" registration of follow-up scan to baseline scan. RESULTS: Stepwise multiple linear regression, adjusted for age and sex, showed that increased CSF p-tau levels (beta [standard error]: -0.79 [0.35]) at baseline was independently associated with higher subsequent hippocampal atrophy rates (p < 0.05), together with poorer memory performance (0.09 [0.04]) and more severe MTA (-0.60 [0.21]). The association of memory function with hippocampal atrophy rate was explained by the link with diagnosis, because it disappeared from the model after we additionally corrected for diagnosis. CONCLUSIONS: Baseline CSF levels of tau phosphorylated at threonine 181 are independently associated with subsequent disease progression, as reflected by hippocampal atrophy rate. This effect is independent of baseline neuropsychological and MRI predictors. Our results imply that predicting disease progression can best be achieved by combining information from different modalities.",Aged;Alzheimer Disease/*cerebrospinal fluid/*pathology/physiopathology;Amino Acid Sequence;Amyloid beta-Peptides/analysis/cerebrospinal fluid;Atrophy/etiology/*pathology/physiopathology;Biomarkers/analysis/cerebrospinal fluid;Disease Progression;Female;Hippocampus/*pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/diagnosis/etiology;Middle Aged;Neuropsychological Tests;Phosphorylation;Predictive Value of Tests;Sensitivity and Specificity;Severity of Illness Index;Threonine/chemistry/metabolism;tau Proteins/analysis/*cerebrospinal fluid,"Henneman, W. J.;Vrenken, H.;Barnes, J.;Sluimer, I. C.;Verwey, N. A.;Blankenstein, M. A.;Klein, M.;Fox, N. C.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.",2009,Sep 22,10.1212/WNL.0b013e3181b879ac,0,
3920,Degradation of cognitive timing mechanisms in behavioural variant frontotemporal dementia,"The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimers disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical-cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype.","Aged;Alzheimer Disease/physiopathology;Aphasia, Primary Progressive/physiopathology;Cerebellar Cortex/ pathology;Female;Frontotemporal Dementia/ physiopathology;Humans;Male;Middle Aged;Motor Activity/ physiology;Time Perception/ physiology","Henley, S. M.;Downey, L. E.;Nicholas, J. M.;Kinnunen, K. M.;Golden, H. L.;Buckley, A.;Mahoney, C. J.;Crutch, S. J.",2014,Dec,10.1016/j.neuropsychologia.2014.10.009,0,
3921,A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO),"Although specific patterns of technetium-99m exametazime [99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for 99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n = 21), confirmed Alzheimer's disease (n = 10), multi-infarct dementia (n = 9), HIV-related dementia (n = 7), or ""mixed"" (n = 3). In addition 20 normal (five per institution) 99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated 99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.","AIDS Dementia Complex/epidemiology/ radionuclide imaging;Alzheimer Disease/epidemiology/ radionuclide imaging;Brain/ radionuclide imaging;Dementia, Multi-Infarct/epidemiology/ radionuclide imaging;Humans;Observer Variation;Organotechnetium Compounds;Oximes;Sensitivity and Specificity;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Hellman, R. S.;Tikofsky, R. S.;Van Heertum, R.;Coade, G.;Carretta, R.;Hoffmann, R. G.",1994,Apr,,0,
3922,Pratical Single Photon Emission Computed Tomography (SPECT) for the community hospital,"Single Photon Emission Computed Tomography (SPECT) can be used to image the cross-sectional distribution of radiopharmaceuticals in the body. In this way, the SPECT technique both improves image contrasts and provides more complete three dimensional information. Both detection and localization of lesions are improved. Information not available through the use of either traditional planar nuclear medicine techniques or other imaging modalities is provided. In particular, the following diagnostic benefits may be achieved: (1) improved detection of lesions responsible for back, hip, knee, and TMJ pain, (2) improved detection and characterization of liver hemangiomas, (3) improved detection of both coronary artery disease and myocardial infarctions, and (4) relatively inexpensive regional cerebral blood flow (rCBF) studies for detection of cerebrovascular disease, Alzheimer's disease, and the full functional consequences of head trauma.",,"Hellman, R. S.;Collier, B. D.;Krasnow, A. Z.;Kir, M.",1990,1990,,0,
3923,PET imaging in ischemic cerebrovascular disease: current status and future directions,"Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large (""malignant"") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases. © 2014 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg.",receptor;marker;amyloid;molecular marker;brain ischemia;brain metabolism;dementia;cerebrovascular accident;imaging;cerebrovascular disease;implantable cardioverter defibrillator;infarction;cognitive defect;multiinfarct dementia;vascularization;tissues;morphology;brain;preservation;biomedicine;perfusion;technology;brain function;metabolic disorder;parameters;positron emission tomography;planning;artery;arteriosclerosis;degenerative disease;nervous system inflammation;invasive procedure;Germany,"Heiss, W. D.",2014,,10.1007/s12264-014-1463-y,0,3924
3924,PET imaging in ischemic cerebrovascular disease: current status and future directions,"Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large (""malignant"") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases. © 2014 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg.",,"Heiss, W. D.",2014,,,0,
3925,"Apolipoprotein E genotype, gender and age modulate connectivity of the hippocampus in healthy adults","Important risk factors for Alzheimer's disease (AD) are ageing and the Apolipoprotein E (APOE) epsilon4 allele, with female APOE epsilon4 carriers having the greatest risk. In this study we investigated effects of AD risk factors on connectivity of the hippocampus, a structure that shows early AD related pathology. Resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 86 cognitively healthy subjects aged 30 to 78years were analysed. Female APOE epsilon4 carriers showed overall significantly reduced functional connectivity between the hippocampus and precuneus/posterior cingulate cortex (PCC) and a significant age-related decrease in connectivity of these regions. In females and APOE epsilon4 carriers we found significantly reduced white matter integrity of the tract connecting the hippocampus and PCC with a significant positive correlation of white matter integrity and resting-state connectivity. Increased vulnerability of the connection between the hippocampus and PCC might be one reason for increased AD risk in female APOE epsilon4 carriers. Interventions targeting hippocampal connectivity might be especially effective in this at risk population.",Adult;Age Factors;Aged;Alzheimer Disease/ genetics;Apolipoprotein E4/ genetics;Brain Mapping;Diffusion Tensor Imaging;Female;Genotype;Gyrus Cinguli/anatomy & histology/ physiology;Healthy Volunteers;Hippocampus/anatomy & histology/ physiology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology/physiopathology;Risk Factors;Sex Factors;White Matter/pathology,"Heise, V.;Filippini, N.;Trachtenberg, A. J.;Suri, S.;Ebmeier, K. P.;Mackay, C. E.",2014,Sep,10.1016/j.neuroimage.2014.04.081,0,
3926,The APOE varepsilon4 allele modulates brain white matter integrity in healthy adults,"The Apolipoprotein E (APOE) varepsilon4 allele is the best-established genetic risk factor for sporadic Alzheimer's disease, and is also associated with structural gray matter and functional brain changes in healthy young, middle-aged and elderly subjects. Because APOE is implicated in brain mechanisms associated with white matter (WM) development and repair, we investigated the potential role played by the APOE polymorphism on WM structure in healthy younger (aged 20-35 years) and older (aged 50-78 years) adults using diffusion tensor imaging. General reduction of fractional anisotropy and increase in mean diffusivity values was found in carriers of the APOE varepsilon4 allele relative to non-carriers. No significant interactions between genotype and age were observed, suggesting that differences in WM structure between APOE varepsilon4-carriers and non-carriers do not undergo significant differential changes with age. This result was not explained by differences in brain morphology or cognitive measures. The APOE varepsilon4 allele modulates brain WM structure before any clinical or neurophysiological expression of impending disease.","Adult;Age Factors;Aged;Alleles;Anisotropy;Apolipoprotein E4/genetics/ physiology;Brain/ anatomy & histology;Diffusion Tensor Imaging/methods/statistics & numerical data;Female;Genotype;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ physiology;Nerve Fibers, Unmyelinated/physiology","Heise, V.;Filippini, N.;Ebmeier, K. P.;Mackay, C. E.",2011,Sep,10.1038/mp.2010.90,0,
3927,Relationships Between Lower Olfaction and Brain White Matter Lesions in Elderly Subjects with Mild Cognitive Impairment,"BACKGROUND: Olfactory impairment is reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and is associated with hippocampal atrophy. In elderly people, dementia with AD neuropathology and white matter lesions (WML) is common. In this context, olfactory impairment could also depend on the presence of WML. OBJECTIVE: To assess the cross-sectional relationship between olfaction and WML in elderly subjects with MCI. METHODS: Consecutive subjects, >65 years old, diagnosed as MCI after a comprehensive neuropsychological assessment in an expert memory center, with a brain MRI performed within a year and without major depressive state, were included. Olfaction was assessed by the Brief Smell Identification Test (BSIT). Two trained neuroradiologists, blind to cognitive and olfaction status, visually assessed hippocampal atrophy according to Scheltens' scale and WML according to Fazekas criteria. RESULTS: Seventy-five MCI subjects (mean age (SD) = 77.1 (6.2) years, 74.7% of women) were included. After adjustment for age and sex, factors associated with low BSIT scores were older age (p = 0.007), lower BMI (p = 0.08), lower MMSE score (p = 0.05), lower FCRST (p = 0.008), hippocampal atrophy (p = 0.04), periventricular WML (p = 0.007), and deep WML burden (p = 0.005). In multivariate analysis, severe deep WML (OR (95% CI) = 6.29 (1.4-35.13), p = 0.02) remained associated with low BSIT score independently from hippocampal atrophy. CONCLUSION: In elderly MCI subjects, low olfactory performances are associated with WML, whose progression may be slowed by vascular treatments. A longitudinal study to evaluate whether the progression of WML, hippocampal atrophy and low olfactory function, can predict accurately conversion from MCI to dementia is ongoing.",Brain white matter lesions;magnetic resonance imaging;mild cognitive impairment;olfaction,"Heinrich, J.;Vidal, J. S.;Simon, A.;Rigaud, A. S.;Hanon, O.;Epelbaum, J.;Viollet, C.;Duron, E.",2018,,,0,
3928,Three-decade neurological and neurocognitive follow-up of HIV-1-infected patients on best-available antiretroviral therapy in Finland,"OBJECTIVES: Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986-1990, in 1997 and in 2013. SETTING: Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases. PARTICIPANTS: The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other. RESULTS: Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23-30) years. Blood CD4 cells at the diagnosis were 610 (29-870) cells/mm(3), and the nadir CD4 168 (4-408) cells/mm(3). The time on combined antiretroviral treatment was 13 (5-17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected. CONCLUSIONS: Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV-seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations.",Infectious diseases,"Heikinheimo, T.;Poutiainen, E.;Salonen, O.;Elovaara, I.;Ristola, M.",2015,,10.1136/bmjopen-2015-007986,0,
3929,Large Virchow-Robin spaces: MR-clinical correlation,"High-field MR scans frequently show Virchow-Robin spaces, which conform to the path of the penetrating arteries as they enter either the basal ganglia or the cortical gray matter over the high convexities. A retrospective review of 816 MR scans was undertaken to determine the clinical significance and associations (if any) of this finding. The Virchow-Robin spaces were graded, as were the nonspecific white-matter lesions. The presence of atrophy, infarction, hydrocephalus, and miscellaneous disease was noted. Large Virchow-Robin spaces were identified in 314 cases. A study sample was created consisting of a positive group containing all the larger grade 2 and 3 Virchow-Robin spaces (67 patients) and a negative or control group of 109 randomly selected patients from the original 502 who did not have large Virchow-Robin spaces. The charts of this study sample were reviewed and the following patient variables were noted: age, gender, incidental white-matter lesions, infarction, dementia, hypertension, and atrophy. For each variable, the proportion of patients who were positive for that variable was calculated for each of the two groups and compared across groups by using a Fisher exact test. Multiple logistic regression analysis was used to determine whether any of these variables were jointly associated with being ""positive"" or ""negative"" for large Virchow-Robin spaces. Some variables were strongly associated with being positive for large Virchow-Robin spaces: age, hypertension, dementia, and incidental white-matter lesions. Logistic regression analysis revealed that when all of these variables are considered jointly, only age remains significant.(ABSTRACT TRUNCATED AT 250 WORDS)","Adolescent;Adult;Aged;Aged, 80 and over;Aging/*pathology;Basal Ganglia/pathology;Brain/blood supply/*pathology;Cerebral Arteries/pathology;Cerebrovascular Disorders/pathology;Child;Child, Preschool;Female;Humans;Infant;Infant, Newborn;*Magnetic Resonance Imaging;Male;Middle Aged;Regression Analysis;Subarachnoid Space/pathology","Heier, L. A.;Bauer, C. J.;Schwartz, L.;Zimmerman, R. D.;Morgello, S.;Deck, M. D.",1989,Sep-Oct,,0,
3930,White matter hyperintensities and chronicity of depression,"OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic resonance imaging (MRI) of the brain are associated with advanced age and late-life depression. Most investigations predominantly found these lesions in frontal lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction in depression. A prospective study was undertaken to investigate the association between extent of WMHs and clinical outcome in elderly depressed patients. METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI scan. The MRI scans were analysed in consensus by two experienced radiologists. Each MRI scan was assessed for presence and extent of WMHs, which are differentiated in periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31 patients were re-assessed 5 years after baseline assessment. We ascertained the severity of depressive symptoms, the longitudinal course of depression, the cognitive decline and the global assessment of functioning at follow-up visit. RESULTS: (1) Subjects with greater extent of WMHs had a significant higher Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal courses of depression (3) and had a lower Mini-Mental State Examination (MMSE) score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly depressed subjects. Further studies are needed to evaluate WHMs as prognostic factor for an appropriate treatment decision-making.","Aged;Basal Ganglia/pathology/physiopathology;Brain/ pathology/ physiopathology;Cerebral Ventricles/pathology/physiopathology;Chronic Disease;Corpus Striatum/pathology/physiopathology;Decision Making;Depressive Disorder, Major/ pathology/ physiopathology;Female;Frontal Lobe/pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Prospective Studies;Severity of Illness Index","Heiden, A.;Kettenbach, J.;Fischer, P.;Schein, B.;Ba-Ssalamah, A.;Frey, R.;Naderi, M. M.;Gulesserian, T.;Schmid, D.;Trattnig, S.;Imhof, H.;Kasper, S.",2005,May,10.1016/j.jpsychires.2004.07.004,0,
3931,Intravascular lymphomatosis of the nervous system (IVL-NS),"We report on a typical case of intravascular lymphomatosis, a rarely diagnosed, generalised intravascular lymphoma usually of the B-cell type. In most cases there is a lack of clear haematological findings but in more than 50 % intravascular lymphomatosis presents with symptoms of the central nervous system. Every rapidly progressive neurological deficit, especially the association of a subacute dementia with a spinal syndrome may suggest IVL-NS. However, careful examination may detect minor features for a systemic process in 25- 80 % i.e. B-symptoms elevation of ESR and LDH. Neurological imaging demonstrates multifocal lesions in the CNS with affinity to the deep white matter consistent with a microvascular or demyelinating disease. Angiographically IVL-NS may mimic cerebral vasculitis. CSF findings are nonspecific. Because diagnosis can only be made histologically, a cerebral biopsy should be undertaken in suspected cases. Usually the course of the disease is fatal. Therapy involving steroids, combination polychemotherapy or radiation met with only minor success.",,"Heesen, C.;Bergmann, M.;Figge, C.;Löschke, S.;Feldmann, M.",1996,1996,,0,
3932,Automatic morphometry in Alzheimer's disease and mild cognitive impairment,"This paper presents a novel, publicly available repository of anatomically segmented brain images of healthy subjects as well as patients with mild cognitive impairment and Alzheimer's disease. The underlying magnetic resonance images have been obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. T1-weighted screening and baseline images (1.5T and 3T) have been processed with the multi-atlas based MAPER procedure, resulting in labels for 83 regions covering the whole brain in 816 subjects. Selected segmentations were subjected to visual assessment. The segmentations are self-consistent, as evidenced by strong agreement between segmentations of paired images acquired at different field strengths (Jaccard coefficient: 0.802+/-0.0146). Morphometric comparisons between diagnostic groups (normal; stable mild cognitive impairment; mild cognitive impairment with progression to Alzheimer's disease; Alzheimer's disease) showed highly significant group differences for individual regions, the majority of which were located in the temporal lobe. Additionally, significant effects were seen in the parietal lobe. Increased left/right asymmetry was found in posterior cortical regions. An automatically derived white-matter hypointensities index was found to be a suitable means of quantifying white-matter disease. This repository of segmentations is a potentially valuable resource to researchers working with ADNI data.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Brain Mapping/ methods;Cognition Disorders/ pathology;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging;Male;Middle Aged","Heckemann, R. A.;Keihaninejad, S.;Aljabar, P.;Gray, K. R.;Nielsen, C.;Rueckert, D.;Hajnal, J. V.;Hammers, A.",2011,Jun 15,10.1016/j.neuroimage.2011.03.014,0,
3933,Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand,"This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naïve, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naïve, individuals with normal cognitive function (HIV+HAND−) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83–324), and mean (IQR) log10 plasma viral load of 4.81 (4.39–5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND− groups or between HIV+/HAND− and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND− suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.",brain;brain atrophy;brain size;cognition;corpus callosum;diagnosis;diseases;gray matter;HIV associated dementia;human;Human immunodeficiency virus;immunosuppressive treatment;neuroimaging;nuclear magnetic resonance imaging;patient;plasma;Thailand;thalamus;therapy;virus load;white matter;CD4 antigen,"Heaps, J. M.;Sithinamsuwan, P.;Paul, R.;Lerdlum, S.;Pothisri, M.;Clifford, D.;Tipsuk, S.;Catella, S.;Busovaca, E.;Fletcher, J. L. K.;Raudabaugh, B.;Ratto-Kim, S.;Valcour, V.;Ananworanich, J.;On Behalf Of The Search 007/011 Study, Groups",2015,,10.1007/s13365-014-0309-8,0,
3934,Association between brain volumes and HAND in cART-naïve HIV+ individuals from Thailand,"This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naïve, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naïve, individuals with normal cognitive function (HIV+HAND−) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83–324), and mean (IQR) log(10) plasma viral load of 4.81 (4.39–5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND− groups or between HIV+/HAND− and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND− suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.",,"Heaps, J. M.;Sithinamsuwan, P.;Paul, R.;Lerdlum, S.;Pothisri, M.;Clifford, D.;Tipsuk, S.;Catella, S.;Busovaca, E.;Fletcher, J. L. K.;Raudabaugh, B.;Ratto-Kim, S.;Valcour, V.;Ananworanich, J.;On Behalf Of The Search 007/011 Study, G.",2015,,,0,
3935,Association between brain volumes and HAND in cART-naive HIV+ individuals from Thailand,"This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naive, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naive, individuals with normal cognitive function (HIV+HAND-) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83-324), and mean (IQR) log10 plasma viral load of 4.81 (4.39-5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND- groups or between HIV+/HAND- and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND- suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.",AIDS Dementia Complex/*pathology;Adult;Atrophy/pathology;Brain/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Organ Size;Thailand,"Heaps, J. M.;Sithinamsuwan, P.;Paul, R.;Lerdlum, S.;Pothisri, M.;Clifford, D.;Tipsuk, S.;Catella, S.;Busovaca, E.;Fletcher, J. L.;Raudabaugh, B.;Ratto-Kim, S.;Valcour, V.;Ananworanich, J.",2015,Apr,10.1007/s13365-014-0309-8,0,
3936,Neuroimaging markers of human immunodeficiency virus infection in South Africa,"Previous studies have reported cognitive deficits among HIV-positive individuals infected with clade C virus. However, no study has examined whether individuals predominately infected with clade C virus exhibit brain atrophy relative to healthy controls. This study examined volumetric differences between 28 HIV+ individuals and 23 HIV- controls from South Africa. Volumetric measures were obtained from six regions of interest -- caudate, thalamus, corpus callosum, total cortex, total gray matter, and total white matter. HIV+ participants had significantly lower volumes in the total white matter (p<0.01), thalamus (p<0.01) and total gray matter (inclusive of cortical and subcortical regions, p<0.01). This study is the first to provide evidence of brain atrophy among HIV+ individuals in South Africa, where HIV clade C predominates. Additional research that integrates neuroimaging, comprehensive neuropsychological testing, genetic variance in clade-specific proteins, and the impact of treatment with Antiretrovirals (ARV) are necessary to understand the development of HIV-related neurocognitive disorders in South Africa.",AIDS Dementia Complex/diagnosis/drug therapy/pathology;Adult;Anti-HIV Agents/administration & dosage/therapeutic use;Brain/*pathology;CD4 Lymphocyte Count;Cognition;Female;HIV/*physiology;HIV Infections/drug therapy/*pathology;Humans;Magnetic Resonance Imaging;Male;Neuroimaging;Neuropsychological Tests;Organ Size;South Africa,"Heaps, J. M.;Joska, J.;Hoare, J.;Ortega, M.;Agrawal, A.;Seedat, S.;Ances, B. M.;Stein, D. J.;Paul, R.",2012,Jun,10.1007/s13365-012-0090-5,0,
3937,Neoplastic angioendotheliomatosis: A treatable 'vascular dementia' occurring in an immunosuppressed transplant patient,"A 53-year-old right-handed woman presented with headaches and dizziness. She had been well for ten years following successful cadaveric renal transplantation and was taking prednisolone and azathioprine. Two months later she had more headaches with transient dominant hemisphere disturbances and then suffered a completed right hemisphere deficit. As this was recovering, she developed an ischemic optic neuropathy, Computerized tomography (CT) was then normal although CSF analysis showed lymphocytosis and high protein. Steroid trial led to dramatic symptomatic and clinical recovery. On tailing off steroids, progressive bilateral hemisphere disturbance occurred. She was bedbound, with fever, headache, incontinence and disturbed consciousness. New evidence of infarction in watershed territories on CT led to temporal lobe biopsy. Cortical arterioles and venules showed proliferation of lymphoid cells staining for leucocyte common antigen and B-cell markers characteristcs of Neoplastic Angioendotheliomatosis (NAE). After chemotherapy she regained independance and mobility and CSF protein fell. This is the first case of NAE to our knowledge in association with immunosuppression for renal transplant and is further evidence that NAE is malignant lymphoma. Cerebrovascular disease is common in such patients, the simultaneous events in differing territories is typical of NAE. Response to chemotherapeutic agents occurred although the typical natural history was unchanged.",azathioprine;cyclophosphamide;dexamethasone;doxorubicin;prednisolone;vincristine;adult;article;case report;female;graft rejection;hemangiomatosis;human;human tissue;immunosuppressive treatment;kidney transplantation;lymphoma;neutropenia,"Heafield, M. T. E.;Carey, M.;Williams, A. C.;Cullen, M.",1993,,,0,
3938,Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease,"Controversy persists regarding whether Alzheimer's disease (AD) is a distinct entity or instead exists on a continuum with nondemented aging. To explore this issue, volumetric analyses of callosal and hippocampal regions were performed on 150 participants aged 18-93 years. Group-level analyses revealed that nondemented age-related differences were greater in anterior than posterior callosal regions and were not augmented by early-stage AD. In contrast, early-stage AD was associated with substantial reduction in hippocampal volume. Examination of the 100 older adults using regression analyses demonstrated age-associated differences in callosal volume that were similar in demented and nondemented individuals. Early-stage AD was again characterized by a marked reduction in hippocampal volume while age alone induced only mild differences in hippocampal volume. As a final analysis, the formal double dissociation was confirmed by comparing the effects of age directly against the effects of dementia. These results suggest a multiple-component model of aging. One process, associated with AD, manifests early and prominently in the medial temporal lobe. A separate process, ubiquitous in aging, affects brain white matter with an anterior-to-posterior gradient and may underlie the executive difficulties common in aging.","Adolescent;Adult;Aged;Aged, 80 and over;Aging/*pathology;Alzheimer Disease/*pathology;Cohort Studies;Corpus Callosum/cytology/*pathology;Female;Hippocampus/cytology/*pathology;Humans;Magnetic Resonance Imaging;Male;Temporal Lobe/cytology/pathology","Head, D.;Snyder, A. Z.;Girton, L. E.;Morris, J. C.;Buckner, R. L.",2005,Jun,10.1093/cercor/bhh174,0,
3939,Differential Vulnerability of Anterior White Matter in Nondemented Aging with Minimal Acceleration in Dementia of the Alzheimer Type: Evidence from Diffusion Tensor Imaging,"White matter microstructural integrity was assessed using diffusion tensor imaging (DTI) in 25 young adults, 25 nondemented older adults, and 25 age-matched older adults with dementia of the Alzheimer type (DAT). For each individual, measures of anisotropy and diffusivity were obtained from atlas-transformed images in the anterior and posterior callosum and in the frontal, parietal, temporal and occipital white matter. These data revealed age differences in anisotropy and diffusivity in all assessed regions. Age effects were greater in the anterior as opposed to the posterior corpus callosum and greater in the frontal white matter than in the temporal, parietal and occipital white matter, suggesting age-associated differences in white matter that exhibit a roughly anterior-to-posterior gradient. In contrast, individuals with early-stage dementia exhibited minimal, if any, additional change in anterior regions but did show greater deterioration of white matter in posterior lobar regions. Taken collectively, these results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions. The dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.",,"Head, D.",2004,April,,0,
3940,"The contributions of MRI-based measures of gray matter, white matter hyperintensity, and white matter integrity to late-life cognition","BACKGROUND AND PURPOSE: GM volume, WMH volume, and FA are each associated with cognition; however, few studies have detected whether these 3 different types of MR imaging measurements exert independent or additive effects on cognitive performance. To detect their extent of contribution to cognitive performance, we explored the independent and additive contributions of GM atrophy, white matter injury, and white matter integrity to cognition in elderly patients. MATERIALS AND METHODS: Two hundred and 9 elderly patients participated in the study: 97 were CN adults, 65 had MCI, and 47 had dementia. We measured GM on T1-weighted MR imaging, WMH on FLAIR, and FA on DTI, along with psychometrically matched measures of 4 domains of cognitive performance, including semantic memory, episodic memory, executive function, and spatial abilities. RESULTS: As expected, patients with dementia performed significantly more poorly in all 4 cognitive domains, whereas patients with MCI performed generally less poorly than dementia patients, though considerable overlap in performance was present across groups. GM, FA, and WMH each differed significantly between diagnostic groups and were associated with cognitive measures. In multivariate models that included all 3 MR imaging measures (GM, WMH, and FA), GM volume was the strongest determinant of cognitive performance. CONCLUSIONS: These results strongly suggest that MR imaging measures of GM are more closely associated with cognitive function than WM measures across a broad range of cognitive and functional impairment.","Aged;Aged, 80 and over;Aging/pathology/ physiology;Brain/cytology/physiology;Cognition/ physiology;Dementia/ diagnosis/pathology/ physiopathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/pathology/ physiology;Neurons/ cytology/physiology","He, J.;Wong, V. S.;Fletcher, E.;Maillard, P.;Lee, D. Y.;Iosif, A. M.;Singh, B.;Martinez, O.;Roach, A. E.;Lockhart, S. N.;Beckett, L.;Mungas, D.;Farias, S. T.;Carmichael, O.;DeCarli, C.",2012,Oct,10.3174/ajnr.A3048,0,
3941,Brain structure and cerebrovascular risk in cognitively impaired patients: Shanghai Community Brain Health Initiative-pilot phase,"OBJECTIVE: To investigate the associations among brain morphologic changes as seen on magnetic resonance imaging (MRI), cerebrovascular risk (CVR), and clinical diagnosis and cognition in elderly patients with mild cognitive impairment and dementia living in urban Shanghai. DESIGN: Cross-sectional study performed from May 1, 2007, to November 31, 2008. SETTING: Memory Disorders Clinic of the Huashan Hospital and the Shanghai community. PARTICIPANTS: Ninety-six older people: 32 with normal cognition (NC), 30 with amnestic mild cognitive impairment (aMCI), and 34 with dementia. MAIN OUTCOME MEASURES: For each patient, we administered a neurologic and physical examination, neuropsychological evaluation, and brain MRI and genotyped the apolipoprotein E-epsilon4 (APOE-epsilon4) gene. The volumes determined by MRI were assessed using a semiautomatic method. RESULTS: Brain volume was significantly smaller in the dementia patients compared with the NC (P < .001) and aMCI patients (P = .04). Hippocampal volume (HV) was lower and white matter hyperintensity (WMH) volume was higher in those with aMCI (HV: P = .03; WMH volume: P = .04) and dementia (HV: P < .001; WMH volume: P = .002) compared with NC participants. The presence of APOE-epsilon4 was significantly associated with reduced HV (P = .02). Systolic blood pressure was positively associated with CVR score (P = .04); diastolic blood pressure (P = .02) and CVR score (P = .04) were positively associated with WMH volume. The WMH volume (P = .03) and CVR score (P = .03) were higher among dementia patients compared with NC participants. CONCLUSIONS: Brain structure changes seen on MRI were significantly associated with clinical diagnosis. In addition, blood pressure was highly associated with CVR score and WMH volume. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular diseases.",Aged;Brain/ pathology;Cerebrovascular Disorders/ epidemiology/pathology;China;Cognition Disorders/diagnosis/ epidemiology/ pathology;Cross-Sectional Studies;Dementia/epidemiology/pathology;Female;Humans;Logistic Models;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neurologic Examination/methods;Neuropsychological Tests;Odds Ratio;Physical Examination;Retrospective Studies;Risk Factors;Urban Population,"He, J.;Iosif, A. M.;Lee, D. Y.;Martinez, O.;Chu, S.;Carmichael, O.;Mortimer, J. A.;Zhao, Q.;Ding, D.;Guo, Q.;Galasko, D.;Salmon, D. P.;Dai, Q.;Wu, Y.;Petersen, R. C.;Hong, Z.;Borenstein, A. R.;DeCarli, C.",2010,Oct,10.1001/archneurol.2010.230,0,
3942,Influence of functional connectivity and structural MRI measures on episodic memory,"Age-related memory decline is the consequence of multiple biological factors that lead to brain structural and functional change, including gray matter atrophy, white matter injury, and loss of functional coordination between regions. However, the independent roles that each of these brain changes play in mediating memory decline is not clear. Therefore, we used magnetic resonance imaging (MRI) to measure gray matter (GM) volume, white matter hyperintensity (WMH) volumes, and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging-based functional connectivity among default mode network nodes in 76 cognitive normal older adults. We found that GM, WMH, and connectivity between left inferior parietal and medial prefrontal cortex (MPF_LIP) were independently associated with episodic memory performance. Within the group with GM volumes below the median, greater MPF_LIP connectivity was associated with better memory performance, whereas this association was not present for individuals with GM volume above the median. These findings confirm the heterogeneous nature of brain-behavior relationships in cognitive aging. In addition, the relationship between resting state functional connectivity and memory performance, particularly amongst those individuals with more brain atrophy, strongly suggests compensation against the effects of neuronal injury. © 2012 Elsevier Inc.",,"He, J.;Carmichael, O.;Fletcher, E.;Singh, B.;Iosif, A. M.;Martinez, O.;Reed, B.;Yonelinas, A.;DeCarli, C.",2012,November,,0,
3943,The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder caused by mutations in the NOTCH3 gene. Although CADASIL scale is a widely used tool to screen clinically suspected CADASIL patients, the differential effects of this scale in various populations remain unknown. METHODS: 92 CADASIL-like patients and 24 CADASIL patients were selected based on CADASIL scale and gene tests. The clinical, genetic and radiological characteristics were analyzed. RESULTS: Based on the CADASIL scale, we first screened 116 suspected CADASIL patients, and detected 20 mutations in 24 CADASIL-patients (Specificity: 20.69 %). Surprisingly, we found that transient ischemic attack/stroke, migraine, cognitive decline, psychiatric disturbances and early onset age in CADASIL scale showed no differences between the CADASIL and the CADASIL-like patients (p > 0.05). Instead, recurrent cerebral ischemic events (58.33 %, p = 0.028) and positive family histories (p < 0.05) were more frequently observed in CADASIL patients. Moreover, compared with CADASIL-like patients (21.74 %), CADASIL patients demonstrated higher percentage of temporal pole involvements (58.33 %, p = 0.001), but not the external capsule involvements (66.67 %, p = 0.602), in MRI imaging. Further, we found that vascular risk factors could occur in both CADASIL patients and CADASIL-like patients, and therefore could not be used as the markers to differentiate the two groups in our study (p > 0.05). By performing DSA analysis, we for the first time identified dysplasia of cerebral blood vessels in CADASIL patients, which were detected more frequently in CADASIL patients (41.67 %) in comparison with CADASIL-like patients (8.69 %, p <0.01). CONCLUSION: Our data suggested that the efficacy of CADASIL scale to diagnose the disease varied with specific populations. Recurrent cerebral ischemic events, temporal pole involvements (but not the external capsule) in MRI imaging and dysplasia of cerebral blood vessels in DSA may be the new potential risk factors of the CADASIL scale suitable for Chinese patients. Gene testing by encephalopathy gene panel is expected to improve the accuracy of CADASIL differential diagnosis and increase the understanding of this disease in the future.","0 (NOTCH3 protein, human);0 (Receptor, Notch3);0 (Receptors, Notch);Adult;Aged;Asian Continental Ancestry Group/ genetics;CADASIL/epidemiology/ genetics/physiopathology;China/epidemiology;DNA Mutational Analysis;Diagnosis, Differential;Female;Genetic Testing;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Migraine Disorders/epidemiology/ genetics/physiopathology;Mutation;Patient Selection;Phenotype;Receptor, Notch3;Receptors, Notch/ genetics;Risk Factors;Stroke/epidemiology/ genetics/physiopathology;Cadasil;CADASIL scale;Small vessel disease","He, D.;Chen, D.;Li, X.;Hu, Z.;Yu, Z.;Wang, W.;Luo, X.",2016,,,0,
3944,Associations between reaction time measures and white matter hyperintensities in very old age,"In old age, a relationship has been reported between intraindividual variability (IIV) in reaction time and white matter integrity as evidenced by white matter hyperintensities (WMH). However, it is unclear how far such associations are due to incipient neurodegenerative pathology in the samples investigated. The present study examined the relationship between IIV and WMH in older individuals (N=526) drawn from the Sydney Memory and Ageing Study. Using a complex reaction time (RT) task, greater IIV and mean-RT were related to a higher WMH burden in the frontal lobe. Critically, significant associations remained having taken future dementia into account suggesting that they were not explained by incipient dementia. Additionally, independent measures of executive function accounted for the association between RT metrics and WHM. The results are consistent with the view that frontally-supported cognitive processes are involved in IIV-WMH relations, and that RT measures are sensitive to compromise in white matter structures in non-demented older individuals.",age;aged;article;dementia;executive function;female;frontal lobe;human;human experiment;male;memory;normal human;nuclear magnetic resonance imaging;response time;very elderly;white matter;white matter hyperintensity,"Haynes, B. I.;Bunce, D.;Kochan, N. A.;Wen, W.;Brodaty, H.;Sachdev, P. S.",2017,,10.1016/j.neuropsychologia.2017.01.021,0,
3945,Progressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sjögren syndrome,"We report progressive multifocal leukoencephalopathy (PML) and CD4+ T-lymphocytopenia in a 71-year-old man with Sjögren syndrome (SjS). The patient was admitted to our hospital because of progressive dementia and gait disturbance. T2-weighted MR images showed high-intensity lesions in his left frontal white matter thalamus, cerebellum and brainstem. A pathological diagnosis of PML was made by brain biopsy. SjS is frequently accompanied with immunological complications; however, there are few reports on PML in patients with SjS. Recently, isolated CD4+ T-lymphocytopenia is reported to be one of the based immunological conditions associated with the development of PML. In the present case, CD4+ T-lymphocytopenia was also observed on admission, which is also associated with SjS. © 2007 Elsevier B.V. All rights reserved.",,"Hayashi, Y.;Kimura, A.;Kato, S.;Koumura, A.;Sakurai, T.;Tanaka, Y.;Hozumi, I.;Sunden, Y.;Orba, Y.;Sawa, H.;Takahashi, H.;Inuzuka, T.",2008,15,,0,
3946,Kinetics of neurodegeneration based on a risk-related biomarker in animal model of glaucoma,"BACKGROUND: Neurodegenerative diseases including Parkinson's and Alzheimer's diseases progress slowly and steadily over years or decades. They show significant between-subject variation in progress and clinical symptoms, which makes it difficult to predict the course of long-term disease progression with or without treatments. Recent technical advances in biomarkers have facilitated earlier, preclinical diagnoses of neurodegeneration by measuring or imaging molecules linked to pathogenesis. However, there is no established ""biomarker model"" by which one can quantitatively predict the progress of neurodegeneration. Here, we show predictability of a model with risk-based kinetics of neurodegeneration, whereby neurodegeneration proceeds as probabilistic events depending on the risk. RESULTS: We used five experimental glaucomatous animals, known for causality between the increased intraocular pressure (IOP) and neurodegeneration of visual pathways, and repeatedly measured IOP as well as white matter integrity by diffusion tensor imaging (DTI) as a biomarker of axonal degeneration. The IOP in the glaucomatous eye was significantly increased than in normal and was varied across time and animals; thus we tested whether this measurement is useful to predict kinetics of the integrity. Among four kinds of models of neurodegeneration, constant-rate, constant-risk, variable-risk and heterogeneity models, goodness of fit of the model and F-test for model selection showed that the time course of optic nerve integrity was best explained by the variable-risk model, wherein neurodegeneration kinetics is expressed in an exponential function across cumulative risk based on measured IOP. The heterogeneity model with stretched exponential decay function also fit well to the data, but without statistical superiority to the variable-risk model. The variable-risk model also predicted the number of viable axons in the optic nerve, as assessed by immunohistochemistry, which was also confirmed to be correlated with the pre-mortem integrity of the optic nerve. In addition, the variable-risk model identified the disintegrity in the higher-order visual pathways, known to underlie the transsynaptic degeneration in this disease. CONCLUSIONS: These findings indicate that the variable-risk model, using a risk-related biomarker, could predict the spatiotemporal progression of neurodegeneration. This model, virtually equivalent to survival analysis, may allow us to estimate possible effect of neuroprotection in delaying progress of neurodegeneration.","Animals;Diffusion Tensor Imaging;Disease Models, Animal;Glaucoma/ pathology/ physiopathology;Intraocular Pressure;Kinetics;Nerve Degeneration/ pathology;Risk Factors","Hayashi, T.;Shimazawa, M.;Watabe, H.;Ose, T.;Inokuchi, Y.;Ito, Y.;Yamanaka, H.;Urayama, S.;Watanabe, Y.;Hara, H.;Onoe, H.",2013,,10.1186/1750-1326-8-4,0,
3947,"Structural brain abnormalities in women with subclinical depression, as revealed by voxel-based morphometry and diffusion tensor imaging","BACKGROUND: Brain structural changes accompany major depressive disorder, but whether subclinical depression is accompanied by similar changes in brain volume and white matter integrity is unknown. By using voxel-based morphometry (VBM) of the gray matter and tract-specific analysis based on diffusion tensor imaging (DTI) of the white matter, we explored the extent to which abnormalities could be identified in specific brain structures of healthy adults with subclinical depression. METHODS: The subjects were 21 community-dwelling adults with subclinical depression, as measured by their Center for Epidemiologic Studies Depression Scale (CES-D) scores. They were not demented and had no neurological or psychiatric history. We collected brain magnetic resonance images of the patients and of 21 matched control subjects, and we used VBM to analyze the differences in regional gray matter volume between the two groups. Moreover, we examined the white matter integrity by using tract-specific analysis based on the gray matter volume changes revealed by VBM. RESULTS: VBM revealed that the volumes of both anterior cingulate gyri and the right rectal gyrus were smaller in subclinically depressed women than in control women. Calculation of DTI measures in the anterior cingulum bundle revealed a positive correlation between CES-D scale score and radial diffusivity in the right anterior cingulum in subclinically depressed women. LIMITATIONS: The small sample size limits the stability of the reported findings. CONCLUSIONS: Gray matter volume reduction and white matter integrity change in specific frontal brain regions may be associated with depressive symptoms in women, even at a subclinical level.","Adult;Aged;Brain/ abnormalities/pathology;Case-Control Studies;Depression/ pathology;Diffusion Tensor Imaging/instrumentation/methods;Female;Gyrus Cinguli/abnormalities;Humans;Middle Aged;Nerve Fibers, Myelinated/pathology;Nerve Fibers, Unmyelinated/pathology;Sample Size","Hayakawa, Y. K.;Sasaki, H.;Takao, H.;Mori, H.;Hayashi, N.;Kunimatsu, A.;Aoki, S.;Ohtomo, K.",2013,Jan 25,10.1016/j.jad.2012.10.023,0,
3948,Depressive symptoms and neuroanatomical structures in community-dwelling women: A combined voxel-based morphometry and diffusion tensor imaging study with tract-based spatial statistics,"Depressive symptoms, even at a subclinical level, have been associated with structural brain abnormalities. However, previous studies have used regions of interest or small sample sizes, limiting the ability to generalize the results. In this study, we examined neuroanatomical structures of both gray matter and white matter associated with depressive symptoms across the whole brain in a large sample. A total of 810 community-dwelling adult participants underwent measurement of depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). The participants were not demented and had no neurological or psychiatric history. To examine the gray and white matter volume, we used structural MRI scans and voxel-based morphometry (VBM); to examine the white matter integrity, we used diffusion tensor imaging with tract-based spatial statistics (TBSS). In female participants, VBM revealed a negative correlation between bilateral anterior cingulate gray matter volume and the CES-D score. TBSS showed a CES-D-related decrease in fractional anisotropy and increase in radial and mean diffusivity in several white matter regions, including the right anterior cingulum. In male participants, there was no significant correlation between gray or white matter volume or white matter integrity and the CES-D score. Our results indicate that the reduction in gray matter volume and differences in white matter integrity in specific brain regions, including the anterior cingulate, are associated with depressive symptoms in women.","Adult;Aged;Aged, 80 and over;Brain/ pathology;Data Interpretation, Statistical;Depression/ pathology;Diffusion Tensor Imaging/ methods;Female;Gray Matter/ pathology;Humans;Image Interpretation, Computer-Assisted/ methods;Middle Aged;Multimodal Imaging/methods;Reproducibility of Results;Sensitivity and Specificity;White Matter/ pathology;Young Adult","Hayakawa, Y. K.;Sasaki, H.;Takao, H.;Hayashi, N.;Kunimatsu, A.;Ohtomo, K.;Aoki, S.",2014,,10.1016/j.nicl.2014.03.002,0,
3949,Diffusion tensor imaging correlates of cognitive-motor decline in normal aging and increased Alzheimer's disease risk,"Alzheimer's disease (AD) is typically associated with impairments in memory and other aspects of cognition, while deficits in complex movements are commonly observed later in the course of the disease. Recent studies, however, have indicated that subtle deteriorations in visuomotor control under cognitively demanding conditions may in fact be an early identifying feature of AD. Our previous work has shown that the ability to perform visuomotor tasks that rely on visual-spatial and rule-based transformations is disrupted in prodromal and preclinical AD. Here, in a sample of 30 female participants (10 young: mean age = 26.6 ± 2.7, 10 low AD risk: mean age = 58.7 ± 5.6, and 10 high AD risk: mean age = 58.5 ± 6.9), we test the hypothesis that these cognitive-motor impairments are associated with early",,"Hawkins, K. M.;Goyal, A. I.;Sergio, L. E.",2015,2015,,0,
3950,Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients,"Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively ""normal"" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE epsilon4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.",Cerebrovascular disease;Cognition;Dementia risk;Hypertension;Type 2 diabetes;White matter hyperintensity volume,"Hawkins, K. A.;Emadi, N.;Pearlson, G. D.;Winkler, A. M.;Taylor, B.;Dulipsingh, L.;King, D.;Pittman, B.;Blank, K.",2017,Jun,,0,
3951,Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients,"Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively ""normal"" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24 h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24 h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE epsilon4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.",Cerebrovascular disease;Cognition;Dementia risk;Hypertension;Type 2 diabetes;White matter hyperintensity volume,"Hawkins, K. A.;Emadi, N.;Pearlson, G. D.;Winkler, A. M.;Taylor, B.;Dulipsingh, L.;King, D.;Pittman, B.;Blank, K.",2017,Mar 03,,0,3950
3952,Pathological findings correlated with MRI in HIV infection,"MRI forms an important part of the assessment of patients with HIV-related disease presenting with cerebral symptoms. Eleven formalin-fixed brains were studied at 0.5 T using T2- and T1-weighted sequences. In two cases of progressive multifocal leucoencephalopathy and one case each of toxoplasmosis and lymphoma, the extent of white matter abnormality seen on MRI corresponded broadly with that on pathological examination. In general, however, histological changes were more frequent than lesions on MRI. Cases in which abnormalities were not seen with standard MRI included those with multiple tuberculous granulomata, multinucleate giant cells, microglial nodules, perivascular cuffing and cytomegalovirus inclusions. A common finding on MRI was punctate or patchy high signal in the basal ganglia on T2-weighted scans, seen in six cases. Corresponding histological changes included calcification of vessels with widened perivascular spaces, and mineralised neurones.","AIDS Dementia Complex/*diagnosis/pathology;AIDS-Related Opportunistic Infections/diagnosis/pathology;Adult;Brain/pathology;Brain Neoplasms/diagnosis/pathology;Cytomegalovirus Infections/diagnosis/pathology;Female;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/pathology;Lymphoma, AIDS-Related/diagnosis/pathology;Male;Middle Aged;Toxoplasmosis, Cerebral/diagnosis/pathology","Hawkins, C. P.;McLaughlin, J. E.;Kendall, B. E.;McDonald, W. I.",1993,,,0,
3953,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Argentina,"CADASIL is the most common cause of hereditary stroke and vascular dementia. Published information about this disease in South America is scant. We describe clinical and demographic characteristics of 13 patients (10 families) with CADASIL from Argentina.Methods Medical records, diagnostic tests and family history of patients with CADASIL were reviewed.Results Thirteen patients with CADASIL (10 families) were included. All patients had European ancestry. Initial presentation was stroke in most patients (n = 11). Stroke patients later developed cognitive complaints (n = 9), migraine with aura (n = 1), apathy (n = 4) and depression (n = 6). External capsule and temporal lobe involvement on MRI were characteristic imaging findings. Two patients died after intracerebral hemorrhage.Conclusion This is the first report of non-related patients with CADASIL in South America addressing ancestry. Since European ancestry is not highly prevalent in all South American countries, there may be variable incidence of CADASIL within this region.",Adult;Aged;Argentina;Biopsy;Brain/ pathology;CADASIL/ complications/ diagnosis/ethnology;Cerebral Arterial Diseases;European Continental Ancestry Group;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies;Stroke/ethnology/ etiology,"Hawkes, M. A.;Wilken, M.;Bruno, V.;Pujol-Lereis, V.;Povedano, G.;Saccoliti, M.;Taratuto, A.;Ameriso, S. F.",2015,Sep,10.1590/0004-282x20150113,0,
3954,Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia Aging study,"BACKGROUND AND PURPOSE: Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors. METHODS: Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974. In the period from 1991 to 1993, dementia status was added to the fourth examination, and a brain MRI was completed in a fifth examination, which was from 1994 to 1996, on a subset of 575 men, who averaged 82 years. WMLs and ventricular atrophy were determined as the upper fifth in a standardized semiquantitative measure. Excess SBP variability was defined as greater than average increases in BP measurements from up to 3 examinations over 6 years. Logistic regression was used for the association of this variability with WMLs and atrophy, controlling for age, apolipoprotein E4 status, dementia diagnosis, and history of stroke. RESULTS: There were significant (2-fold) increased risks for WMLs among those with moderate and high SBP variability (third and fifth quintiles compared with the lowest quintile). Those in the highest SBP variability category (the fifth quintile) also had significantly more atrophy. CONCLUSIONS: These SBP variability-MRI relationships suggest that variation in SBP in midlife may be a contributing factor to the development of WMLs and ventricular atrophy in late life.",Age Factors;Aged;Asian Americans;Atrophy/pathology;*Blood Pressure;Brain/pathology;Brain Diseases/ethnology/*etiology/*pathology;Cerebral Ventricles/pathology;Cohort Studies;Dementia/diagnosis;Genetic Variation;Hawaii/epidemiology;Humans;Japan/ethnology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Systole,"Havlik, R. J.;Foley, D. J.;Sayer, B.;Masaki, K.;White, L.;Launer, L. J.",2002,Jan,,0,
3955,"A 91 year old man with a stroke, hypertension, and renal failure","We report a 91 year old man who had a stroke and died of renal failure. He had been treated for hypertension since 20 years before the onset of the present illness. In addition, he was operated on a gastric cancer 17 years previously. Otherwise he was doing well until May 29, 1991 (when he was 87 year old) when he had sudden onset of dysarthria and right facial weakness. He was admitted to our hospital. On admission, general physical examination was unremarkable, and neurologic examination revealed a mentally sound man with slight dysarthria, right facial weakness, orolingual dyskinesia, and disequilibrium in which he showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A cranial CT scan revealed leukoaraiosis with multiple low density areas in the cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic symptoms cleared within the next few weeks and he was discharged with ticlopidine 100 mg q.d.. He had been doing well after the discharge except for gradual worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April of 1994. On March 10, 1995, he fell down and hit his back; he became unable to walk because of pain, and he was admitted again on March 16, 1995. On admission, his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema; otherwise general physical examination was unremarkable. Neurologic examination revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30. Higher cerebral functions as well as cranial nerves were intact. He showed some unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration was diminished in the feet, however, pain and touch sensations were intact. Laboratory examination revealed a compression fracture of the twelfth thoracic vertebra. Blood count and chemistries were as follows: Hb 7.6 g/dl, Hct 23.3%, TP 6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T Chol 174 mg/dl, HDL Chol 49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 MEq/L. A urine specimen contained 1 + protein and 1 + glucose and the sediments contained hyaline casts. A cranial CT scan was essentially same as that taken four years ago. His hospital course was complicated with pneumonia, congestive heart failure, and progressive renal failure. He was treated with intravenous fluid, chemotherapy, and other supportive measures, however, he expired from respiratory failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease in the brain, benign nephrosclerosis from arteriosclerosis due to hypertension, congestive heart failure, and pneumonia. Opinions were divided regarding the question as to whether or not this patient had Binswanger's disease. Although his cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was only mild until his fall on March, 1995. Clinical features did not conform to those of Binswanger's disease. Postmortem examination of the right hemisphere revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also seen in the coronary arteries and the left middle cerebral artery with 70% stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters with scattered small infarcts. Arterioles in the white matter showed arteriolosclerosis. Small infarcts were also seen in the putamen and in the thalamus. This patient appeared to have had circulatory disturbance of the white matter which is the basic abnormality causing the Binswanger's disease. However, white matter changes in this patient were not quite severe enough to make a pathologic diagnosis of Binswanger's disease.",ticlopidine;aged;arteriosclerosis;article;Binswanger encephalopathy;case report;computer assisted tomography;congestive heart failure;dysarthria;dyskinesia;edema;facial nerve paralysis;gait disorder;human;hypertension;kidney failure;male;nephrosclerosis;pneumonia;stomach cancer;cerebrovascular accident;spine fracture;white matter,"Hattori, Y.;Motoi, Y.;Mori, H.;Takase, S.;Suda, K.;Imai, H.;Mizuno, Y.",1996,,,0,
3956,Gradual Carotid Artery Stenosis in Mice Closely Replicates Hypoperfusive Vascular Dementia in Humans,"BACKGROUND: Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention. METHODS AND RESULTS: Adult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel-constricting device with an inner diameter of 0.75 mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28 days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28-day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28 days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32 days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y-maze test showed working memory deficits. CONCLUSIONS: The GCAS model successfully generated gradual and continuous CBF reduction over 28 days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI.","Animals;Behavior, Animal;Brain/ blood supply/pathology/physiopathology;Carotid Arteries/pathology/ physiopathology;Carotid Stenosis/etiology/ physiopathology/psychology;Cerebral Angiography/methods;Cerebrovascular Circulation;Cognition;Cognition Disorders/etiology/ physiopathology/psychology;Collateral Circulation;Dementia, Vascular/ physiopathology/psychology;Disease Models, Animal;Disease Progression;Humans;Magnetic Resonance Angiography;Male;Maze Learning;Mice, Inbred C57BL;Motor Activity;Perfusion Imaging/methods;Phenotype;Regional Blood Flow;Rotarod Performance Test;Species Specificity;Time Factors;ameroid constrictor;carotid artery stenosis;mouse;subcortical ischemic vascular dementia;vascular cognitive impairment","Hattori, Y.;Enmi, J.;Iguchi, S.;Saito, S.;Yamamoto, Y.;Tsuji, M.;Nagatsuka, K.;Kalaria, R. N.;Iida, H.;Ihara, M.",2016,Feb 22,,0,
3957,Altered microstructure in corticospinal tract in idiopathic normal pressure hydrocephalus: Comparison with Alzheimer disease and Parkinson disease with dementia,"BACKGROUND AND PURPOSE: Previous neuropathologic studies in chronic hydrocephalus have suggested the presence of white matter damage, presumably from mechanical pressure due to ventricular enlargement and metabolic derangement. This study aimed to investigate the diffusional properties of the CST in patients with iNPH by using DTI and to determine whether this method could be used as a new diagnostic tool to differentiate patients with iNPH from those with AD and PDD and control subjects. MATERIALS AND METHODS: We enrolled 18 patients with iNPH, 11 patients with AD, 11 patients with PDD, and 19 healthy control subjects. Diffusion tensor metrics of the segmented CST, including FA values, axial eigenvalues, and radial eigenvalues, were evaluated by using tract-specific analysis. The anisotropy color-coding tractography of the CST was visually evaluated. The DTI findings were compared among groups. RESULTS: Tract-specific analysis of the CST showed that FA values and axial eigenvalues were significantly increased (P < .001), whereas radial eigenvalues were not significantly altered, in patients with iNPH compared with other subjects. The CST tractographic images in patients with iNPH was visually different from those in other subjects (P < .001). In discriminating patients with iNPH from other subjects, the CST FA values had a sensitivity of 94% and specificity of 80% at a cutoff value of 0.59. CONCLUSIONS: Our results suggest that patients with iNPH have altered microstructures in the CST. Quantitative and visual CST evaluation by using DTI may be useful for differentiating patients with iNPH from patients with AD or PDD or healthy subjects.",,"Hattori, T.;Yuasa, T.;Aoki, S.;Sato, R.;Sawaura, H.;Mori, T.;Mizusawa, H.",2011,October,,0,
3958,A 40-year-old woman with progressive dementia and abnormal behavior,"We report a 40-year-old Japanese woman who died after 12 years history of progressive dementia and abnormal behaviors. She was well until 1985 at her age of 28 years old, when she had an onset of behavioral change in which she drank much, neglected house-keeping works, and her life style became sloppy. At age 30, she became unable to understand written sentences, and paced up- and down in and out of her house. She was admitted to other hospital where marked dementia with disorientation and memory loss were noted. Slight increase in CSF protein and decrease in the peripheral nerve conduction velocity were also noted at that time. In the next year, she started to have convulsions. These symptoms had progressively become worse and was admitted to Tokyo Metropolital Matsuzawa Hospital in June of 1991 when she was 34 years of age. Despite marked dementia, she was able to walk normally; no motor paralysis, cerebellar ataxia, nor dyskinesia were noted. Deep tendon reflexes were diminished. MRI revealed T-2 high signal intensity lesions involving the white matter of the cerebrum predominantly in the frontal region. In about one year, she started to show difficulty in gait, and she became bed-ridden in July of 1994. She was discharged to home for a while, but required admission again. She expired on February 5, 1998. Her younger brother had an essentially similar dementing disease and he expired at the age of 35 years. The parents were of first cousins. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had adult form of metachromatic leukodystrophy, because of white matter change in the frontal lobe, decrease in nerve conduction velocity, convulsion, marked dementia, and consanguineous marriage with a similarly affected brother. Most of the audience agreed with this conclusion, but the differential diagnosis from globoid cell leukodystrophy was felt difficult from the clinical findings alone. Post-mortem examination revealed marked atrophy in the frontal lobe. Cerebellum appeared to be smaller than normal. In the coronal sections, marked atrophy of the white matter with brown discoloration was noted. The lateral ventricles were dilated. Kluver-Barrera staining revealed marked demyelination with relative preservation of the U-fibers. PAS-positive materials were deposited in some astrocytes as well as neurons. Metachromatic deposites were noted not only in the cerebrum but also cerebellum after staining with acid cresyl violet. Pathologic diagnosis was consistent with adult type of metachromatic leukodystrophy.",adult;amnesia;article;autopsy;behavior disorder;brain lateral ventricle;brain ventricle dilatation;case report;consanguineous marriage;dementia;disorientation;female;frontal lobe;human;metachromatic leukodystrophy;white matter,"Hattori, T.;Tanaka, S.;Shimo, Y.;Anno, M.;Ohta, S.;Ishi, K.;Mori, H.;Ohkuma, Y.;Mizuno, Y.",1999,,,0,
3959,Cognitive status correlates with white matter alteration in Parkinson's disease,"Patients with Parkinson's disease (PD) can develop mild cognitive impairment (PD-MCI), frequently progressing to dementia (PDD). Here, we aimed to elucidate the relationship between white matter alteration and cognitive status in PD and dementia with Lewy bodies (DLB) by using diffusion tensor imaging. We also compared the progression patterns of white and gray matter and the cerebral perfusion. We enrolled patients with PD cognitively normal (PD-CogNL, n = 32), PD-MCI (n = 28), PDD (n = 25), DLB (n = 29), and age- and sex-matched healthy control subjects (n = 40). Fractional anisotropy (FA) map of a patient group was compared with that of control subjects by using tract-based spatial statistics. For the patient cohort, intersubject voxel-wise correlation was performed between FA values and Mini-Mental Status Examination (MMSE) scores. We also evaluated the gray matter and the cerebral perfusion by conducting a voxel-based analysis. There were significantly decreased FA values in many major tracts in patients with PD-MCI, PDD, and DLB, but not in PD-CogNL, compared with control subjects. FA values in the certain white matter areas, particularly the bilateral parietal white matter, were significantly correlated with MMSE scores in patients with PD. Patients with PDD and DLB had diffuse gray matter atrophy. All patient groups had occipital and posterior parietal hypoperfusion when compared with control subjects. Our results suggest that white matter damage underlies cognitive impairment in PD, and cognitive impairment in PD progresses with functional alteration (hypoperfusion) followed by structural alterations in which white matter alteration precedes gray matter atrophy.","Aged;Aged, 80 and over;Anisotropy;Brain/ pathology;Brain Mapping;Cognition/physiology;Cognition Disorders/etiology/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Interpretation, Computer-Assisted;Male;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/complications/ pathology","Hattori, T.;Orimo, S.;Aoki, S.;Ito, K.;Abe, O.;Amano, A.;Sato, R.;Sakai, K.;Mizusawa, H.",2012,Mar,10.1002/hbm.21245,0,
3960,White matter alteration in idiopathic normal pressure hydrocephalus: Tract-based spatial statistics study,"BACKGROUND AND PURPOSE: White matter alteration in iNPH has not been well-investigated. TBSS is a voxelwise statistical analysis developed for DTI data. We aimed to elucidate the cerebral white matter alteration in patients with iNPH by using DTI and to test the accuracy of TBSS analysis. MATERIALS AND METHODS: DTI data were obtained from 20 patients with iNPH and 20 age- and sex-matched controls. The FA values were evaluated by using TBSS, region-of-interest and tract-specific analysis of the CST. The accuracy of TBSS analysis was tested by using ""back-projection"" of TBSS results and by comparing the TBSS analysis results with those of region-of-interest and tract-specific analysis. RESULTS: Back-projection of the TBSS results showed accurate registration of the whole brain, with the exception of parts of the thalamus, fornix, and white matter around the posterior body of the lateral ventricle. The TBSS analysis results were consistent with those of the region-of-interest analysis and tract-specific analysis. In patients with iNPH compared with control subjects, the FA values were significantly decreased in parts of the corpus callosum, periventricular white matter, and juxtacortical white matter in the frontal and parietal lobes. In contrast, FA values were significantly increased in the internal capsule, extending to the white matter in the centrum semiovale. CONCLUSIONS: Our results suggest that patients with iNPH have various patterns of white matter damage and that TBSS analysis is a promising tool for performing accurate voxelwise statistical analysis of the iNPH brain, with the exception of misregistered areas.",aged;article;clinical article;clinical feature;controlled study;dementia;diffusion tensor imaging;echo planar imaging;female;gait disorder;human;idiopathic disease;male;Mini Mental State Examination;neuroimaging;normotensive hydrocephalus;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;urine incontinence;white matter;Sigan Excite,"Hattori, T.;Ito, K.;Aoki, S.;Yuasa, T.;Sato, R.;Ishikawa, M.;Sawaura, H.;Hori, M.;Mizusawa, H.",2012,,,0,
3961,Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease,"To investigate metabolic changes in Alzheimer's disease (AD), we performed proton MR spectroscopy at 3T Spectra were acquired from the gray matter of the posterior cingulate gyrus and the precuneus, and from the parietooccipital white matter in nine AD patients and 12 controls. In patients, the N-acetyl group (NA)/creatine + phosphocreatine (Cr) ratios were decreased in both regions, and a decrease in the glutamate + glutamine (Glx)/Cr ratio and a correlation between the NA/Cr and Glx/Cr ratios were detected in the gray matter, but not in the white matter. These results suggest that NA and Glx metabolism are simultaneously affected in AD, however, metabolic changes in Glx are more profound in the gray matter than in the white matter.",Aged;Alzheimer Disease/*metabolism;Aspartic Acid/*analogs & derivatives/metabolism;Brain/*metabolism;Creatine/metabolism;Female;Glutamic Acid/*metabolism;Glutamine/*metabolism;Humans;Magnetic Resonance Imaging;*Magnetic Resonance Spectroscopy/methods;Male;Phosphocreatine/metabolism;Reference Values;Tissue Distribution,"Hattori, N.;Abe, K.;Sakoda, S.;Sawada, T.",2002,Jan 21,,0,
3962,Development of automated measurement method for medial temporal lobe on CT images,"Recent research has suggested that the measurement of regional atrophy in the structure of the medial temporal lobe is a promising way to discriminate Alzheimer-type dementia patients from healthy control subjects. The purpose of this study was to develop a technique to measure the medial temporal lobe automatically in axial CT images. Linear measurements of width of the inferior horns of the lateral ventricles, width of the medial temporal lobe, and the interuncal distance were performed. Area measurements of the inferior horns of the lateral ventricles were also performed. In the algorithm for the automatic measurement of the medial temporal lobe, brain contour, and sagittal plane were detected first, and the inferior horns of the lateral ventricles. Our method was applied to ten patients clearly without cerebral hemorrhage or infarct. The rates of accuracy of automated detection were 93% with the linear measurements and 75% with the area of the inferior horns. The rates were improved to 100% with the variable function of the threshold value. We suggest that this automated measurement method is both objective and simple enough to be used in routine clinical applications.","Adolescent;Adult;Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/pathology/radiography;Atrophy;Humans;Middle Aged;Temporal Lobe/pathology/ radiography;Tomography, X-Ray Computed/ methods","Hattori, M.;Koyama, S.",2004,Jul,,0,
3963,An elderly patient with an insulinoma who had prolonged dementia-like symptoms,"A 77-year-old woman had suffered from memory disturbance and disorientation for two years before she was admitted to the hospital because of confusion. Her score on the Hasegawa dementia scale revised (HDS-R) was 12 points at the time of the first medical examination. No other abnormalities could be found except for a blood glucose concentration of 34 mg/dl. A Magnetic Resonance Image (MRI) of the brain showed some small lacunae on both sides in the frontal white matter and basal ganglia. After hospitalization, glucose was administered and the blood glucose concentration increased, but the dementia-like symptoms did not resolve. She was discharged because the symptoms were too difficult to control in the general hospital. Although dementia-like symptoms were present even after discharge, they did not necessarily appear during fasting. Six months later she was rehospitalized. The insulin-blood sugar ratio was at least 0.3 and abdominal echogram showed a 1-cm tumor at the tail of pancreas. The pancreas tail was removed and the tumor cells were reacted with antiinsulin-antibodies. One month after the operation, the dementia-like symptoms had resolved. The HDS-R score was improved to 27 points (normal range) 40 days after the operation. The amount of the slow waves in the electroencephalogram decreased 5 months after the operation. The dementia-like symptoms observed in this case could be regarded as the Durchgangssyndrom of Wieck. This syndrome is observed transiently at the time of recovery of deterioration of disturbances of consciousness. But it is treatable. This patient was an interesting case that showed Durchgangssyndrom mimiking dementia associated with insulinoma.",,"Hattori, H.;Matsumoto, M.;Tsuchiya, H.;Iwai, K.;Miyauchi, E.;Takasaki, M.;Munehira, J.;Kawanishi, K.",1998,1998,,0,
3964,Association between cerebral small vessel diseases and mild parkinsonian signs in the elderly with vascular risk factors,"Introduction: The aim of this study was to examine the association between mild parkinsonian signs (MPS), cerebral small-vessel disease (SVD), and total SVD burden in patients with vascular risk factors. Methods: We performed a cross-sectional study among 268 patients with vascular risk factors but without parkinsonism or dementia (71.0 ± 7.8 years, 63% male). MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (cerebral microbleeds [CMBs], lacunar infarctions [LIs], and white matter hyperintensities [WMH]). The presence of each SVD feature was indicated by the total SVD score. Logistic regression analyses were performed adjusting for age, sex, history of stroke, hypertension, diabetes mellitus, and dyslipidemia. Results: In a multivariate analysis, we found that the presence of CMBs, deep CMBs, mixed (in the basal ganglia and thalamus) LIs, periventricular hyperintensities (PVH), and deep WMH (DWMH), and total SVD score were significantly associated with MPS, whereas strictly lobar CMBs and other LIs (in strictly basal ganglia or strictly thalamus) were not. We also found a significant association between mixed LIs, PVH, DWMH and total SVD score and gait/balance function, between PVH and rigidity, and between mixed LIs and bradykinesia. Among elderly participants (≥73years), the association of total SVD score, deep CMBs, mixed LIs, and PVH, with MPS remained significant. Conclusion: Our results provide additional evidence that SVD including CMBs, and especially total SVD burden, might be a surrogate marker for MPS and support the contribution of hypertensive microangiopathy as the underlying etiology.",age distribution;aged;article;basal ganglion;bradykinesia;brain hemorrhage;cerebrovascular accident;cerebrovascular disease;controlled study;cross-sectional study;diabetes mellitus;disease association;dyslipidemia;female;human;hypertension;lacunar stroke;major clinical study;male;medical history;nuclear magnetic resonance imaging;parkinsonism;priority journal;prospective study;risk assessment;risk factor;sex difference;thalamus;Unified Parkinson Disease Rating Scale;white matter lesion,"Hatate, J.;Miwa, K.;Matsumoto, M.;Sasaki, T.;Yagita, Y.;Sakaguchi, M.;Kitagawa, K.;Mochizuki, H.",2016,,10.1016/j.parkreldis.2016.02.011,0,3965
3965,Association between cerebral small vessel diseases and mild parkinsonian signs in the elderly with vascular risk factors,"INTRODUCTION: The aim of this study was to examine the association between mild parkinsonian signs (MPS), cerebral small-vessel disease (SVD), and total SVD burden in patients with vascular risk factors. METHODS: We performed a cross-sectional study among 268 patients with vascular risk factors but without parkinsonism or dementia (71.0 +/- 7.8 years, 63% male). MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (cerebral microbleeds [CMBs], lacunar infarctions [LIs], and white matter hyperintensities [WMH]). The presence of each SVD feature was indicated by the total SVD score. Logistic regression analyses were performed adjusting for age, sex, history of stroke, hypertension, diabetes mellitus, and dyslipidemia. RESULTS: In a multivariate analysis, we found that the presence of CMBs, deep CMBs, mixed (in the basal ganglia and thalamus) LIs, periventricular hyperintensities (PVH), and deep WMH (DWMH), and total SVD score were significantly associated with MPS, whereas strictly lobar CMBs and other LIs (in strictly basal ganglia or strictly thalamus) were not. We also found a significant association between mixed LIs, PVH, DWMH and total SVD score and gait/balance function, between PVH and rigidity, and between mixed LIs and bradykinesia. Among elderly participants (>/=73years), the association of total SVD score, deep CMBs, mixed LIs, and PVH, with MPS remained significant. CONCLUSION: Our results provide additional evidence that SVD including CMBs, and especially total SVD burden, might be a surrogate marker for MPS and support the contribution of hypertensive microangiopathy as the underlying etiology.",,"Hatate, J.;Miwa, K.;Matsumoto, M.;Sasaki, T.;Yagita, Y.;Sakaguchi, M.;Kitagawa, K.;Mochizuki, H.",2016,Feb 13,10.1016/j.parkreldis.2016.02.011,0,
3966,A patient with Hashimoto's encephalopathy showing subacute global cognitive dysfunction,"We report a 66-year-old woman with Hashimoto's encephalopathy who showed rapidly developing cognitive deficits, inactivity, and gait disturbance without involuntary movements or convulsions. She had had right-sided hemiparesis and dysarthria caused by a lacunar infarction and had been admitted to our hospital for 2 weeks. Although the dysarthria and hemiparesis gradually improved, difficulty in walking, disorientation, and drowsiness developed 2 months after discharge. Upon readmission, the patient was alert but apathetic and sometimes sleepy. The right upper and lower limbs showed mild weakness, which was considered to be due to the previous infarction. Cerebrospinal fluid showed mild elevation of protein without pleocytosis. An electroencephalogram was normal, and a magnetic resonance imaging of the brain showed only the old lacunar infarction. Titers of antithyroglobulin antibodies and levels of thyroid stimulating hormone in serum were elevated. We made a diagnosis of Hashimoto's encephalopathy and treated the patient with high-dose corticosteroids. Within 1 week, her mental status improved and she was able to walk. Generalized seizure, myoclonus, and tremor, which are characteristic of Hashimoto's encephalopathy, never developed. The findings in this patient suggest that Hashimoto's encephalopathy, a treatable condition, should be included in the differential diagnosis of dementia.",,"Hatano, Y.;Mori, H.;Kakusaka, K.;Kitada, T.;Urabe, T.;Mizuno, Y.",2003,1,,0,
3967,[Early cerebral lesions in HIV infection. Postmortem radio-pathologic correlations in non-AIDS asymptomatic seropositive patients] Lesions cerebrales precoces au cours de l'infection par le VIH. Correlations radiopathologiques post mortem chez des seropositifs asymptomatiques non SIDA,"In order to evaluate the diagnostic and prognostic value of MRI in the very early stages of HIV infection, we have compared the results of postmortem brain MRI and neuropathological studies in 7 asymptomatic HIV seropositive individuals, 8 seronegative controls with similar cause of death and 6 patients who died of AIDS in the absence of focal cerebral changes (opportunistic infection or tumour). Cerebral atrophy was consistently evaluated by both techniques. Seropositive asymptomatic cases were significantly more atrophic than the seronegative controls and significantly less atrophic than AIDS patients. Small high signal intensity areas in the white matter and basal ganglia were not significantly more frequent in seropositives than in seronegatives. No corresponding lesion was found at neuropathological examination. Diffuse myelin pallor of the cerebral white matter on myelin preparation was somewhat more severe in seropositive asymptomatic cases than in seronegative controls and less than in AIDS cases. However, these differences were not statistically significant. No significant correlation could be found between neuropathological myelin pallor and diffuse signal abnormalities of the white matter on MRI. We conclude that brain abnormalities are present at the early asymptomatic stage of HIV infection. These include vasculitis with opening of the blood brain barrier and consequent myelin pallor and gliosis of the white matter, and moderate brain atrophy. However MRI correlates are discrete or non specific on post mortem examination, and some probably correspond to scars of transient vascular inflammation. It is very unlikely that MRI examination has any diagnostic or prognostic value at the early stages of the disease.",AIDS Dementia Complex/ diagnosis/ pathology;Adult;Atrophy;Autopsy;Basal Ganglia Diseases/diagnosis/pathology;Blood-Brain Barrier;Brain/ pathology;Cerebrovascular Disorders/diagnosis/pathology;Female;Gliosis/diagnosis/pathology;HIV Seronegativity;HIV Seropositivity/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/pathology;Prognosis;Vasculitis/diagnosis/pathology,"Hassine, D.;Gray, F.;Chekroun, R.;Chretien, F.;Marc, B.;Durigon, M.;Schouman-Claeys, E.",1995,Sep,,0,
3968,[Early cerebral lesions in HIV infection. Postmortem radio-pathologic correlations in non-AIDS asymptomatic seropositive patients],"In order to evaluate the diagnostic and prognostic value of MRI in the very early stages of HIV infection, we have compared the results of postmortem brain MRI and neuropathological studies in 7 asymptomatic HIV seropositive individuals, 8 seronegative controls with similar cause of death and 6 patients who died of AIDS in the absence of focal cerebral changes (opportunistic infection or tumour). Cerebral atrophy was consistently evaluated by both techniques. Seropositive asymptomatic cases were significantly more atrophic than the seronegative controls and significantly less atrophic than AIDS patients. Small high signal intensity areas in the white matter and basal ganglia were not significantly more frequent in seropositives than in seronegatives. No corresponding lesion was found at neuropathological examination. Diffuse myelin pallor of the cerebral white matter on myelin preparation was somewhat more severe in seropositive asymptomatic cases than in seronegative controls and less than in AIDS cases. However, these differences were not statistically significant. No significant correlation could be found between neuropathological myelin pallor and diffuse signal abnormalities of the white matter on MRI. We conclude that brain abnormalities are present at the early asymptomatic stage of HIV infection. These include vasculitis with opening of the blood brain barrier and consequent myelin pallor and gliosis of the white matter, and moderate brain atrophy. However MRI correlates are discrete or non specific on post mortem examination, and some probably correspond to scars of transient vascular inflammation. It is very unlikely that MRI examination has any diagnostic or prognostic value at the early stages of the disease.",AIDS Dementia Complex/*diagnosis/*pathology;Adult;Atrophy;Autopsy;Basal Ganglia Diseases/diagnosis/pathology;Blood-Brain Barrier;Brain/*pathology;Cerebrovascular Disorders/diagnosis/pathology;Female;Gliosis/diagnosis/pathology;HIV Seronegativity;HIV Seropositivity/pathology;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/pathology;Prognosis;Vasculitis/diagnosis/pathology,"Hassine, D.;Gray, F.;Chekroun, R.;Chretien, F.;Marc, B.;Durigon, M.;Schouman-Claeys, E.",1995,Sep,,0,
3969,Stroke of the inferiomedial temporal lobe causing word agnosia,"A 69-year-old man presented with sudden loss of ability to recognise written words and remember the meaning of words and names. He could not name the town he lived in nor name his children. It was difficult for him to remember the meaning of concrete and abstract nouns. His speech fluency and understanding of casual talks were normal. He remembered that he had a conversation with his family that morning, but not the exact content. He was referred to the transient ischaemic attack clinic by his general practitioner as he scored low on the abbreviated mental test score. He underwent a brain MRI scan (T2 weighted, diffusion weighted and fluid-attenuated inversion recovery) which showed an acute infarction in the left medial temporal region affecting the fusiform and parahippocampal gyri. He also noticed that it was easier to retrieve numbers, for example, his mobile number. He recovered on waking up the next day.",dementia;memory disorders(psychiatry);stroke;vascular,"Hassan, H.;Ehsanula, H.;Pattanshetti, M.",2017,Jul 26,,0,
3970,Heidenhain variant of Creutzfeldt-Jakob disease in a patient who had bovine bioprosthetic valve implantation,"Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder characterized by rapidly progressing dementia, general neurologic deterioration, and death. When the leading symptoms are visual disturbances, it is termed as the Heidenhain variant of CJD (HvCJD). CJD was reported following prion-contaminated pericardium transplants but never after bovine bioprosthetic cardiac valve. In this case report, we describe HvCJD in a patient who had a bovine bioprosthetic cardiac valve implant. An 82-year-old-woman was referred to neuro-ophthalmology clinic for unexplained visual loss that started 1 month previously. Medical history included aortic valve replacement with bovine bioprosthetic valve. On examination, best-corrected visual acuity was 20/120 in the right eye and 20/200 in the left eye; otherwise, the eye examination was normal. Humphrey visual fields revealed complete right homonymous hemianopsia. Magnetic resonance imaging (MRI) demonstrated nonspecific white matter changes. A week later, she was hospitalized due to memory impairment; repeated MRI and total body computed tomography scan showed no significant findings. Electroencephalography recordings and extremely elevated cerebrospinal fluid tau protein were compatible with CJD. The patient died 3 weeks later; autopsy was not performed. The patient had HvCJD. Ophthalmologists being first to see these patients should be aware of this diagnosis. Contaminated bovine bioprosthetic valve might be another source for prion disease. Further research is required to establish this issue.",,"Hashoul, J.;Saliba, W.;Bloch, I.;Jabaly-Habib, H.",2016,Oct,,0,
3971,Binding of 11C-Pittsburgh compound-B correlated with white matter injury in hypertensive small vessel disease,"OBJECTIVE: 11C-Pittsburgh compound-B (11C-PIB) positron emission tomography (PET) is used to visualize and quantify amyloid deposition in the brain cortex in pathological conditions such as Alzheimer's disease (AD). Intense 11C-PIB retention is also observed in the white matter (WM) of both healthy individuals and AD patients. However, the clinical implications of this retention in brain WM have not been clarified. We investigated the relationship between the extent of white matter lesions (WMLs) and the binding potential of 11C-PIB (BPND) in the WM in patients with hypertensive small vessel disease. We further examined the relationship between the extent of WMLs and BPND in WML and in normal-appearing white matter (NAWM). METHODS: Twenty-one hypertensive vasculopathy patients, without AD and major cerebral arterial stenosis and/or occlusion, were enrolled (9 women, 68 +/- 7 years). Regions of WML and NAWM were extracted using magnetization-prepared rapid gradient-echo and fluid-attenuated inversion recovery of magnetic resonance images. Volumes of interest (VOIs) were set in the cortex-subcortex, basal ganglia, and centrum semiovale (CS). BPND in the cortex-subcortex, basal ganglia, CS, WML, and NAWM were estimated on 11C-PIB PET using Logan graphical analysis with cerebellar regions as references. The relationships between WML volume and BPND in each region were examined by linear regression analysis. RESULTS: BPND was higher in the CS and basal ganglia than in the cortex-subcortex regions. WML volume had a significant inverse correlation with BPND in the CS (Slope = -0.0042, R 2 = 0.44, P < 0.01). For intra WM comparison, BPND in NAWM was significantly higher than that in WML. In addition, although there were no correlations between WML volume and BPND in WML, WML volume was significantly correlated inversely with BPND in NAWM (Slope = -0.0017, R 2 = 0.26, P = 0.02). CONCLUSIONS: 11C-PIB could be a marker of not only cortical amyloid-beta deposition but also WM injury accompanying the development of WMLs in hypertensive small vessel disease.",11C-Pittsburgh compound-B;Binding potential;Positron emission tomography;Small vessel disease;White matter lesion,"Hashimoto, T.;Yokota, C.;Koshino, K.;Temma, T.;Yamazaki, M.;Iguchi, S.;Shimomura, R.;Uehara, T.;Funatsu, N.;Hino, T.;Minematsu, K.;Iida, H.;Toyoda, K.",2017,Apr,,0,
3972,Dual task walking reveals cognitive dysfunction in community-dwelling elderly subjects: the Sefuri brain MRI study,"The aim of our study was to investigate the effects of subclinical brain lesions and cognitive function on gait performance with or without concurrent cognitive task in community-dwelling elderly subjects. Participants without dementia (92 men and 109 women with a mean age of 67.8 years) underwent brain magnetic resonance imaging, neuropsychologic tests, and gait measurements. Impaired gait velocity of the Timed Up and Go test was associated with deep white matter lesions (odds ratio [OR], 2.338; 95% confidence interval [CI], 1.120-4.880) and diabetes mellitus (OR, 2.725; 95% CI, 1.120-6.630) after adjusted for age, sex, education, and cognitive function tests. Impaired gait velocity of dual task walking was associated with age and the score of Rivermead Behavioral Memory Test (OR, .899/1 point higher; 95% CI, .813-.994), whereas deep white matter lesions were not significantly associated with dual task walking. The present study showed that gait represents not only physical functioning but also subclinical cognitive dysfunction particularly memory impairment in healthy elderly subjects.","Aged;Brain/ pathology;Cerebral Small Vessel Diseases/pathology;Cognition Disorders/ pathology/ psychology;Female;Gait Disorders, Neurologic/pathology/psychology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Socioeconomic Factors;Walking/ physiology;White Matter/pathology","Hashimoto, M.;Takashima, Y.;Uchino, A.;Yuzuriha, T.;Yao, H.",2014,Aug,10.1016/j.jstrokecerebrovasdis.2014.05.008,0,
3973,White matter lesion and Alzheimer's disease: The association between small vessel disease and neuropsychiatric symptoms in Alzheimer's disease,"Cerebral small vessel disease (SVD), including subcortical lacunar infarcts (lacunes) and white matter hyperintensities (WMH), is commonly observed on MRI of elderly individuals with and without dementia. SVD is frequently observed in patients with Alzheimer's disease (AD). However, the association between SVD and clinical symptoms exhibited by patients with AD remains unclear. Our recent studies suggest that cerebral SVD observed on CT/MRI of patients with AD is associated with delusions and delirium as well as depression. Mechanisms underlying these psychiatric symptoms in patients with AD remain unclear.",Alzheimer disease;article;brain infarction;cerebrovascular disease;computer assisted tomography;delirium;delusion;depression;disease association;disease course;human;mental disease;neurologic disease;nuclear magnetic resonance imaging;white matter;white matter lesion,"Hashimoto, M.;Ikeda, M.",2015,,,0,
3974,Hippocampal atrophy and memory dysfunction associated with physical inactivity in community-dwelling elderly subjects: The Sefuri study,"BACKGROUND: Physical inactivity is one of the modifiable risk factors for hippocampal atrophy and Alzheimer's disease. We investigated the relationship between physical activity, hippocampal atrophy, and memory using structural equation modeling (SEM). MATERIALS AND METHODS: We examined 213 community-dwelling elderly subjects (99 men and 114 women with a mean age of 68.9 years) without dementia or clinically apparent depression. All participants underwent Mini-Mental State Examination (MMSE) and Rivermead Behavioral Memory Test (RBMT). Physical activities were assessed with a structured questionnaire. We evaluated the degree of hippocampal atrophy (z-score-referred to as ZAdvance hereafter), using a free software program-the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping 8 plus Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra. RESULTS: Routine magnetic resonance imaging findings were as follows: silent brain infarction, n = 24 (11.3%); deep white matter lesions, n = 72 (33.8%); periventricular hyperintensities, n = 35 (16.4%); and cerebral microbleeds, n = 14 (6.6%). Path analysis based on SEM indicated that the direct paths from leisure-time activity to hippocampal atrophy (beta = -.18, p < .01) and from hippocampal atrophy to memory dysfunction (RBMT) (beta = -.20, p < .01) were significant. Direct paths from ""hippocampus"" gray matter volume to RBMT and MMSE were highly significant, while direct paths from ""whole brain"" gray matter volume to RBMT and MMSE were not significant. The presented SEM model fit the data reasonably well. CONCLUSION: Based on the present SEM analysis, we found that hippocampal atrophy was associated with age and leisure-time physical inactivity, and hippocampal atrophy appeared to cause memory dysfunction, although we are unable to infer a causal or temporal association between hippocampal atrophy and memory dysfunction from the present observational study.",Alzheimer's disease;dementia;magnetic resonance imaging;mild cognitive impairment;physical activity,"Hashimoto, M.;Araki, Y.;Takashima, Y.;Nogami, K.;Uchino, A.;Yuzuriha, T.;Yao, H.",2017,Feb,,0,
3975,A family with DRPLA and chronic renal failure,"We reported a family with dentato-rubro-pallido-luysian atrophy (DRPLA) and chronic renal failure. The proband was a 66-year-old woman who developed gait disturbance, limb ataxia, pyramidal tract signs, and dementia since age 54. T2-weighted brain MR images revealed symmetric high-signal lesions in the cerebral white matter, in addition to cerebellar, brainstem, and cerebral cortical atrophy. She suffered from renal failure and became dialysis-dependent at the age of 59, four years after the onset of chronic nephritic syndrome. At the age of 66, she was admitted to our hospital because of hyperthermia and disturbance of consciousness, and died of DIC. Her CAG repeats in the DRPLA gene were 58 and 12. An autopsy was performed. The brain weighed 910 g. Histological findings confirmed the diagnosis of DRPLA. Her mother died of chronic renal failure. All three siblings had cerebellar ataxia, and two siblings trod chronic nephritic syndrome. Among them, only her younger brother was diagnosed as non-IgA glomerulonephritis based on kidney biopsy findings at the age of 48. Though the nature of the association between DRPLA and renal dysfunction remains obscure, the DRPLA gene abnormality may be correlated with chronic renal failure in this family.",,"Hashiguchi, S.;Ogasawara, N.;Mine, H.;Yamamoto, A.;Numata, A.;Ogino, T.",2000,2000,,0,
3976,Case of optic neuritis associated with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL),"PURPOSE: To report a case of optic neuritis associated with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). CASE: A 38-year-old woman presented with visual field defects, ocular pain and relative afferent papillary defect (RAPD). Fluorescein angiography demonstrated peripapillary hyperfluorescence of the optic nerve. Optic neuritis was diagnosed soon after. Routine laboratory data were unremarkable. Brain MRI showed a remarkable enhanced region of white matter and abnormal spots in the capsula externa. Multiple sclerosis was outruled by neurological findings and therefore CARASIL was diagnosed according to the criteria. The patient's vision and inflammation of the optic nerve head gradually improved with systemic steroid therapy, but arterial sheathing was observed during the follow-up period. CONCLUSIONS: Clinical manifestations such as optic neuritis and retinal vascular change might be caused by the pathological changes of CARASIL. This is the first report of ophthalmic findings of clinicopathological events of CARASIL.",adult;article;brain infarction;case report;female;genetics;human;multiinfarct dementia;optic neuritis;progressive multifocal leukoencephalopathy;recessive gene;retina vasculitis;syndrome,"Hashida, N.;Ito, S.;Hasegawa, T.;Kajita, T.;Morifuji, H.;Yamazaki, Y.;Sakagami, K.;Yokotani, S.;Tanaka, T.;Endoh, B.;Egawa, N.;Inoue, H.;Tomimoto, H.;Takahashi, R.",2009,,,0,
3977,"Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome","BACKGROUND AND PURPOSE: Eosinophilia myalgia syndrome (EMS), a multisystemic disease induced by exposure to L-tryptophan, may result in serious CNS abnormalities. The purpose of this study was to determine the pattern of neurologic characteristics, MR imaging abnormalities, and brain neurometabolites in EMS. METHODS: Sixteen patients with EMS and CNS abnormalities (CNS-EMS) and 12 control subjects underwent evaluation, including medical and neurologic examination, proton MR spectroscopy, and MR imaging. RESULTS: Neurologic findings that were increased in CNS-EMS included minor depression (100%), amnesia (88%), and intermittent confusion (38%), although fatigue (31%), motor disorders (31%), recurrent headache (19%), major depression (13%), and dementia (6%) also occurred, but at a lesser significance. Self-reported disability was markedly increased in CNS-EMS. MR imaging findings included subcortical focal lesions, focal lesions in deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities. MR spectroscopic findings established two distinct spectral patterns: 1) increased choline-containing compounds, decreased N-acetylaspartate, and increased lipid-macromolecules, consistent with inflammatory cerebrovascular disease; and 2) increased glutamine, decreased myo-inositol, and decreased choline, consistent with acute CNS injury or metabolic encephalopathy. CONCLUSION: Neurologic abnormalities, self-reported disability, brain lesions, and MR spectroscopic abnormalities are common in CNS-EMS. The pattern of cerebral lesions and neurometabolites is consistent with widespread inflammatory cerebrovascular disease. However, a subgroup of patients with CNS-EMS have neurometabolic changes consistent with a metabolic encephalopathy identical or similar to hepatic encephalopathy. The neurologic abnormalities in EMS and related hypereosinophilic syndromes should be interpreted cautiously, with the recognition that both cerebrovascular injury and secondary metabolic encephalopathies may be involved.",,"Haseler, L. J.;Sibbitt Jr, W. L.;Sibbitt, R. R.;Hart, B. L.",1998,October,,0,
3978,Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan,"Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p = 0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p = 0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI.","Aged;Angiotensin-Converting Enzyme Inhibitors/*therapeutic use;Antihypertensive Agents/*therapeutic use;Blood Pressure/*drug effects;Brain/radiography;Cerebral Infarction/*drug therapy/*physiopathology;Diastole;Disease Progression;Diuretics/therapeutic use;Double-Blind Method;Drug Therapy, Combination;Female;Follow-Up Studies;Humans;Indapamide/therapeutic use;Japan;Male;Middle Aged;Perindopril/*therapeutic use;Secondary Prevention;Stroke/*prevention & control;Tomography, X-Ray Computed;Treatment Outcome","Hasegawa, Y.;Yamaguchi, T.;Omae, T.;Woodward, M.;Chalmers, J.",2004,Mar,,0,
3979,"Childhood-onset cadasil: Clinical, imaging, and neurocognitive features","CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a progressive neurodegenerative condition, associated with mutations in the notch3 gene. Symptoms include migraine with aura, mood disorders, progressive cognitive decline, subcortical ischemic strokes, dementia, and premature death. We present an 8-year- old boy with attention and behavioral difficulties, as well as a family history of the condition. Magnetic resonance imaging revealed subcortical foci of increased T2 hyperintensity, and sequencing of the notch3 gene revealed 1 previously reported mutation and 1 novel sequence variant. Neurocognitive assessment revealed deficits in several aspects of executive functioning and in verbal learning. To our knowledge, this is the youngest reported patient with this condition, and it prompts reconsideration of CADASIL as an adult-onset disease. © The Author(s) 2010.",,"Hartley, J.;Westmacott, R.;Decker, J.;Shroff, M.;Yoon, G.",2010,May,,0,
3980,Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study,"OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.",Adult;Aged;Aging/pathology/ psychology;Athletes/ psychology;Brain Concussion/diagnosis/epidemiology/psychology;Cognition Disorders/diagnosis/epidemiology/ psychology;Cross-Sectional Studies;Depression/diagnosis/epidemiology/ psychology;Football/ psychology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuroimaging/methods;Retirement/ psychology;Retrospective Studies;Texas/epidemiology;United States/epidemiology,"Hart, J., Jr.;Kraut, M. A.;Womack, K. B.;Strain, J.;Didehbani, N.;Bartz, E.;Conover, H.;Mansinghani, S.;Lu, H.;Cullum, C. M.",2013,Mar 1,10.1001/2013.jamaneurol.340,0,
3981,"Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study","OBJECTIVES: To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS: The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS: This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS: Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychological assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.",AIDS Dementia Complex/*diagnosis/physiopathology/psychology;Acquired Immunodeficiency Syndrome/*diagnosis/physiopathology/psychology;Adult;Aspartic Acid/analogs & derivatives/metabolism;Atrophy;Brain/pathology/physiopathology;CD4 Lymphocyte Count;Choline/metabolism;Cohort Studies;Creatine/metabolism;Cross-Sectional Studies;*Electroencephalography;HIV Seropositivity/*diagnosis/physiopathology/psychology;Humans;Longitudinal Studies;*Magnetic Resonance Imaging;*Magnetic Resonance Spectroscopy;Male;Middle Aged;Neurologic Examination;*Neuropsychological Tests,"Harrison, M. J.;Newman, S. P.;Hall-Craggs, M. A.;Fowler, C. J.;Miller, R.;Kendall, B. E.;Paley, M.;Wilkinson, I.;Sweeney, B.;Lunn, S.;Carter, S.;Williams, I.",1998,Sep,,0,
3982,"Executive function changes before memory in preclinical Alzheimer's pathology: a prospective, cross-sectional, case control study","BACKGROUND: Early treatment of Alzheimer's disease may reduce its devastating effects. By focusing research on asymptomatic individuals with Alzheimer's disease pathology (the preclinical stage), earlier indicators of disease may be discovered. Decreasing cerebrospinal fluid beta-amyloid42 is the first indicator of preclinical disorder, but it is not known which pathology causes the first clinical effects. Our hypothesis is that neuropsychological changes within the normal range will help to predict preclinical disease and locate early pathology. METHODS AND FINDINGS: We recruited adults with probable Alzheimer's disease or asymptomatic cognitively healthy adults, classified after medical and neuropsychological examination. By logistic regression, we derived a cutoff for the cerebrospinal fluid beta amyloid42/tau ratios that correctly classified 85% of those with Alzheimer's disease. We separated the asymptomatic group into those with (n = 34; preclinical Alzheimer's disease) and without (n = 36; controls) abnormal beta amyloid42/tau ratios; these subgroups had similar distributions of age, gender, education, medications, apolipoprotein-epsilon genotype, vascular risk factors, and magnetic resonance imaging features of small vessel disease. Multivariable analysis of neuropsychological data revealed that only Stroop Interference (response inhibition) independently predicted preclinical pathology (OR = 0.13, 95% CI = 0.04-0.42). Lack of longitudinal and post-mortem data, older age, and small population size are limitations of this study. CONCLUSIONS: Our data suggest that clinical effects from early amyloid pathophysiology precede those from hippocampal intraneuronal neurofibrillary pathology. Altered cerebrospinal fluid beta amyloid42 with decreased executive performance before memory impairment matches the deposits of extracellular amyloid that appear in the basal isocortex first, and only later involve the hippocampus. We propose that Stroop Interference may be an additional important screen for early pathology and useful to monitor treatment of preclinical Alzheimer's disease; measures of executive and memory functions in a longitudinal design will be necessary to more fully evaluate this approach.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/ pathology/ physiopathology;Amyloid beta-Peptides/metabolism;Case-Control Studies;Cross-Sectional Studies;Executive Function/physiology;Female;Genotype;Humans;Male;Models, Statistical;Prospective Studies","Harrington, M. G.;Chiang, J.;Pogoda, J. M.;Gomez, M.;Thomas, K.;Marion, S. D.;Miller, K. J.;Siddarth, P.;Yi, X.;Zhou, F.;Lee, S.;Arakaki, X.;Cowan, R. P.;Tran, T.;Charleswell, C.;Ross, B. D.;Fonteh, A. N.",2013,,10.1371/journal.pone.0079378,0,
3983,Cross-sectional and longitudinal multimodal structural imaging in prodromal Huntington’s disease,"Objectives: Diffusivity in white-matter tracts is abnormal throughout the brain in cross-sectional studies of prodromal Huntington's disease. To date, longitudinal changes have not been observed. The present study investigated cross-sectional and longitudinal changes in white-matter diffusivity in relationship to the phase of prodromal Huntington's progression, and compared them with changes in brain volumes and clinical variables that track disease progression. Methods: Diffusion MRI profiles were studied for 2 years in 37 gene-negative controls and 64 prodromal Huntington's disease participants in varied phases of disease progression. To estimate the relative importance of diffusivity metrics in the prodromal phase, group effects were rank ordered relative to those obtained from analyses of brain volumes, motor, cognitive, and sensory variables. Results: First, at baseline diffusivity was abnormal throughout all tracts, especially as individuals approached a manifest Huntington's disease diagnosis. Baseline diffusivity metrics in 6 tracts and basal ganglia volumes best distinguished among the groups. Second, group differences in longitudinal change in diffusivity were localized to the superior fronto-occipital fasciculus, most prominently in individuals closer to a diagnosis. Group differences were also observed in longitudinal changes of most brain volumes, but not clinical variables. Last, increases in motor symptoms across time were associated with greater changes in the superior fronto-occipital fasciculus diffusivity and corpus callosum, cerebrospinal fluid, and lateral ventricle volumes. Conclusions: These novel findings provide new insights into changes within 2 years in different facets of brain structure and their clinical relevance to changes in symptomatology that is decisive for a manifest Huntington's diagnosis. © 2016 International Parkinson and Movement Disorder Society.",adult;article;basal ganglion;brain function;brain size;cerebrospinal fluid;comparative study;controlled study;corpus callosum;cross-sectional study;diffusion weighted imaging;disease course;female;human;Huntington chorea;lateral brain ventricle;longitudinal study;major clinical study;male;neuroimaging;nuclear magnetic resonance scanner;occipitofrontal fasciculus;odor recognition test;outcome assessment;priority journal;prodromal huntington disease;prodromal symptom;Stroop test;symbol digit modalities test;trail making test;Unified Huntington Disease Rating Scale;University of Pennsylvania Smell Identification Test;white matter;TIM Trio 3T,"Harrington, D. L.;Long, J. D.;Durgerian, S.;Mourany, L.;Koenig, K.;Bonner-Jackson, A.;Paulsen, J. S.;Rao, S. M.",2016,,10.1002/mds.26803,0,
3984,The relationship of high-intensity signals on magnetic resonance images to cognitive and psychiatric state in Alzheimer's disease,"In Alzheimer's disease (AD), the relationship between white-matter changes on magnetic resonance images and behavior are unclear. Therefore, magnetic resonance images, cognition, and psychiatric state were assessed in patients with AD with depression (AD/DEP; n = 18) and without depression (AD; n = 45), older depressed patients (n = 12) and older normal individuals (n = 25). High-intensity signals in the cortex and subcortical regions were similar in number and proportions among all groups, even when hypertensive patients were excluded. No correlations to cognitive or psychiatric state were found. Periventricular signals were categorized using a 1- (absent) to 6- (thick, irregular caps and stripes) point scale. The categories were similar among groups except that patients with AD exhibited more category 5 changes than did normal subjects, neuropsychological performance was significantly worse in patients with AD who had category 5 and 6 changes when compared to those in category 1. These results suggest that periventricular changes may predict poor neuropsychological performance in patients with AD. However, neither deep white-matter lesions nor periventricular changes are useful for diagnostic purposes.",Aged;Alzheimer Disease/complications/ diagnosis/psychology;Brain/ pathology;Cognition;Humans;Hypertension/complications/pathology;Magnetic Resonance Imaging;Middle Aged;Neuropsychological Tests,"Harrell, L. E.;Duvall, E.;Folks, D. G.;Duke, L.;Bartolucci, A.;Conboy, T.;Callaway, R.;Kerns, D.",1991,Nov,,0,
3985,Magnetic resonance imaging and the diagnosis of dementia,"We describe seven patients with clinical, laboratory, and CT evidence of primary degenerative dementia (Alzheimer's, Pick's). Magnetic resonance imaging demonstrated regions in the white matter consistent with cerebral infarction. MRI may be a sensitive way to differentiate multi-infarct dementia and primary degenerative dementia.","Aged;Brain/pathology/radiography;Dementia/ diagnosis;Female;Humans;Magnetic Resonance Spectroscopy;Male;Tomography, X-Ray Computed","Harrell, L. E.;Callaway, R.;Sekar, B. C.",1987,Mar,,0,
3986,Brain levels of high-energy phosphate metabolites and executive function in geriatric depression,"OBJECTIVES: Depression in late life has been associated with difficulties in cognitive processing, particularly in the domains of executive function, processing speed and memory, and increases the risk of developing dementia suggesting a neurodegenerative phenotype. Mitochondrial dysfunction is frequently an early event in neurodegenerative illnesses and may be operative in patients with late life depression. Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules produced by mitochondria. METHODS: Ten patients with late life depression and eight normal elderly controls were studied with Stroop color and interference tests, which are widely used measures of processing speed and executive function, respectively, followed by (31P) MRS 3-dimensional chemical-shift imaging measuring levels of adenosine triphosphate, phosphocreatine, inorganic phosphate, and pH over the whole brain. RESULTS: In all subjects, gray matter phosphocreatine was positively associated with Stroop interference. Levels of white matter adenosine triphosphate were associated with Stroop interference in subjects with late life depression but not normal elderly. There was also a complementary association between white matter inorganic phosphate and Stroop interference in late life depression patients. CONCLUSIONS: These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain. The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis. Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects. Copyright (c) 2016 John Wiley & Sons, Ltd.","0 (Biomarkers);0 (Phosphates);020IUV4N33 (Phosphocreatine);8L70Q75FXE (Adenosine Triphosphate);Adenosine Triphosphate/ metabolism;Aged;Aged, 80 and over;Aging/ physiology;Biomarkers/metabolism;Brain/ metabolism;Case-Control Studies;Depressive Disorder/ metabolism;Energy Metabolism;Executive Function/ physiology;Female;Gray Matter/metabolism;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Neuropsychological Tests;Phosphates/ metabolism;Phosphocreatine/ metabolism;White Matter/metabolism;adenosine triphosphate;aging;late life depression;phosphocreatine;processing speed;response inhibition","Harper, D. G.;Joe, E. B.;Jensen, J. E.;Ravichandran, C.;Forester, B. P.",2016,Nov,,0,3987
3987,Brain levels of high-energy phosphate metabolites and executive function in geriatric depression,"OBJECTIVES: Depression in late life has been associated with difficulties in cognitive processing, particularly in the domains of executive function, processing speed and memory, and increases the risk of developing dementia suggesting a neurodegenerative phenotype. Mitochondrial dysfunction is frequently an early event in neurodegenerative illnesses and may be operative in patients with late life depression. Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules produced by mitochondria. METHODS: Ten patients with late life depression and eight normal elderly controls were studied with Stroop color and interference tests, which are widely used measures of processing speed and executive function, respectively, followed by (31P) MRS 3-dimensional chemical-shift imaging measuring levels of adenosine triphosphate, phosphocreatine, inorganic phosphate, and pH over the whole brain. RESULTS: In all subjects, gray matter phosphocreatine was positively associated with Stroop interference. Levels of white matter adenosine triphosphate were associated with Stroop interference in subjects with late life depression but not normal elderly. There was also a complementary association between white matter inorganic phosphate and Stroop interference in late life depression patients. CONCLUSIONS: These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain. The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis. Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects. Copyright (c) 2016 John Wiley & Sons, Ltd.",,"Harper, D. G.;Joe, E. B.;Jensen, J. E.;Ravichandran, C.;Forester, B. P.",2016,Feb 18,10.1002/gps.4439,0,
3988,Scanning laser Doppler flowmetry shows reduced retinal capillary blood flow in CADASIL,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive systemic nonatherosclerotic angiopathy which causes ischemic strokes and vascular subcortical dementia. A cross-sectional study was performed to examine the retinal vascular caliber and blood flow in CADASIL. METHODS: Scanning laser Doppler flowmetry was used in a case-control study (11 patients and controls) of peripapillary retinal circulation. Automated full-field perfusion image analysis was used to analyze the flow data. Retinal vessel calibers were measured from retinal images acquired with scanning laser ophthalmoscopy. The caliber of the superior and inferior temporal retinal artery and vein were measured 1 and 2 mm from the disc rim, and the mean values were used for analysis. RESULTS: Retinal capillary peak systolic flow (mean, 249 versus 311 arbitrary unit [AU]; P=0.072) was lower, and mean capillary flow (mean, 184 versus 224 AU; P=0.12) and minimum diastolic flow (mean, 105 versus 132 AU; P=0.16) tended to be lower in patients than in controls. No significant difference in the calibers of proximal retinal arteries (mean, 104 versus 108 microm) and veins (mean, 150 versus 145 microm) was found between the patients and controls. CONCLUSIONS: Retinal capillary blood flow is mild to moderately reduced in CADASIL but that does not appear to cause major ischemic injury. Such reduction is analogous to that in the cerebral cortex in CADASIL patients with which retina appears to share its relative sparing from severe arterial ischemic tissue damage.",Adult;CADASIL/ physiopathology;Capillaries/physiopathology;Case-Control Studies;Female;Humans;Laser-Doppler Flowmetry;Male;Middle Aged;Regional Blood Flow;Retinal Vessels/ physiopathology,"Harju, M.;Tuominen, S.;Summanen, P.;Viitanen, M.;Poyhonen, M.;Nikoskelainen, E.;Kalimo, H.;Kivela, T.",2004,Nov,10.1161/01.STR.0000145048.94499.b9,0,
3989,T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease,"In the current study, we have evaluated the performance of magnetic resonance (MR) T1rho (T1rho) imaging and CSF biomarkers (T-tau, P-tau and Abeta-42) in characterization of Alzheimer's disease (AD) patients from mild cognitive impairment (MCI) and control subjects. With informed consent, AD (n = 27), MCI (n = 17) and control (n = 17) subjects underwent a standardized clinical assessment and brain MRI on a 1.5-T clinical-scanner. T1rho images were obtained at four different spin-lock pulse duration (10, 20, 30 and 40 ms). T1rho maps were generated by pixel-wise fitting of signal intensity as a function of the spin-lock pulse duration. T1rho values from gray matter (GM) and white matter (WM) of medial temporal lobe were calculated. The binary logistic regression using T1rho and CSF biomarkers as variables was performed to classify each group. T1rho was able to predict 77.3% controls and 40.0% MCI while CSF biomarkers predicted 81.8% controls and 46.7% MCI. T1rho and CSF biomarkers in combination predicted 86.4% controls and 66.7% MCI. When comparing controls with AD, T1rho predicted 68.2% controls and 73.9% AD, while CSF biomarkers predicted 77.3% controls and 78.3% for AD. Combination of T1rho and CSF biomarkers improved the prediction rate to 81.8% for controls and 82.6% for AD. Similarly, on comparing MCI with AD, T1rho predicted 35.3% MCI and 81.9% AD, whereas CSF biomarkers predicted 53.3% MCI and 83.0% AD. Collectively CSF biomarkers and T1rho were able to predict 59.3% MCI and 84.6% AD. On receiver operating characteristic analysis T1rho showed higher sensitivity while CSF biomarkers showed greater specificity in delineating MCI and AD from controls. No significant correlation between T1rho and CSF biomarkers, between T1rho and age, and between CSF biomarkers and age was observed. The combined use of T1rho and CSF biomarkers have promise to improve the early and specific diagnosis of AD. Furthermore, disease progression form MCI to AD might be easily tracked using these two parameters in combination.","Aged;Alzheimer Disease/cerebrospinal fluid/ diagnosis;Amyloid beta-Peptides/cerebrospinal fluid;Area Under Curve;Biomarkers/ cerebrospinal fluid;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Mild Cognitive Impairment/cerebrospinal fluid/ diagnosis;Neuropsychological Tests;ROC Curve;Sensitivity and Specificity;tau Proteins/cerebrospinal fluid","Haris, M.;Yadav, S. K.;Rizwan, A.;Singh, A.;Cai, K.;Kaura, D.;Wang, E.;Davatzikos, C.;Trojanowski, J. Q.;Melhem, E. R.;Marincola, F. M.;Borthakur, A.",2015,,10.1016/j.nicl.2015.02.016,0,
3990,T1ρ MRI in Alzheimer's Disease: Detection of Pathological Changes in Medial Temporal Lobe,"BACKGROUND: The need of an early and noninvasive diagnosis of AD requires the development of imaging-based techniques. As an alternative, the magnetic resonance image (MRI) relaxation time constant (T1ρ) was measured in brains of Alzheimer's disease (AD), mild-cognitive impairment (MCI), and age-matched controls in order to determine whether T1ρ values correlated with the neurological diagnosis. METHODS: MRI was performed on AD (n= 48), MCI (n= 45), and age-matched control (n= 41), on a 1.5 Tesla Siemens clinical MRI scanner. T1ρ maps were generated by fitting each pixel's intensity as a function of the duration of the spin-lock pulse. T1ρ values were calculated from the gray matter (GM) and white matter (WM) of medial temporal lobe (MTL). RESULTS: GM and WM T1ρ values were 87.5 ± 1.2 ms and 80.5 ± 1.4 ms, respectively, in controls, 90.9 ± 1.3 ms and 84.1 ± 1.7 ms in MCI, and 91.9 ± .8 ms and 88.3 ± 1.3 ms in AD cohorts. Compared to control, AD patients showed 9% increased WM T1ρ and 5% increased GM T1ρ. Compared to control, MCI individuals showed 4% increased T1ρ both in WM and GM. A 5% increased T1ρ was found in WM of AD over MCI. CONCLUSION: The increased T1ρ in WM and GM of MTL in AD may be associated with the pathological changes that are not evident on conventional MRI. © 2010 by the American Society of Neuroimaging.",adult;aged;Alzheimer disease;article;clinical article;controlled study;female;gray matter;human;male;medial temporal lobe;mild cognitive impairment;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;relaxation time constant;temporal lobe;white matter,"Haris, M.;Singh, A.;Cai, K.;McArdle, E.;Fenty, M.;Davatzikos, C.;Trojanowski, J. Q.;Melhem, E. R.;Clark, C. M.;Borthakur, A.",2011,,,0,
3991,T(1rho) MRI in Alzheimer's disease: detection of pathological changes in medial temporal lobe,"BACKGROUND: The need of an early and noninvasive diagnosis of AD requires the development of imaging-based techniques. As an alternative, the magnetic resonance image (MRI) relaxation time constant (T1rho) was measured in brains of Alzheimer's disease (AD), mild-cognitive impairment (MCI), and age-matched controls in order to determine whether T1rho values correlated with the neurological diagnosis. METHODS: MRI was performed on AD (n=48), MCI (n=45), and age-matched control (n=41), on a 1.5 Tesla Siemens clinical MRI scanner. T1rho maps were generated by fitting each pixel's intensity as a function of the duration of the spin-lock pulse. T1rho values were calculated from the gray matter (GM) and white matter (WM) of medial temporal lobe (MTL). RESULTS: GM and WM T1rho values were 87.5+/-1.2 ms and 80.5+/-1.4 ms, respectively, in controls, 90.9+/-1.3 ms and 84.1+/-1.7 ms in MCI, and 91.9+/-.8 ms and 88.3+/-1.3 ms in AD cohorts. Compared to control, AD patients showed 9% increased WM T1rho and 5% increased GM T1rho. Compared to control, MCI individuals showed 4% increased T1rho both in WM and GM. A 5% increased T1rho was found in WM of AD over MCI. CONCLUSION: The increased T1rho in WM and GM of MTL in AD may be associated with the pathological changes that are not evident on conventional MRI.","Aged;Alzheimer Disease/ pathology;Analysis of Variance;Case-Control Studies;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Temporal Lobe/ pathology","Haris, M.;Singh, A.;Cai, K.;McArdle, E.;Fenty, M.;Davatzikos, C.;Trojanowski, J. Q.;Melhem, E. R.;Clark, C. M.;Borthakur, A.",2011,Apr,10.1111/j.1552-6569.2010.00467.x,0,
3992,In vivo mapping of brain myo-inositol,"Myo-Inositol (MI) is one of the most abundant metabolites in the human brain located mainly in glial cells and functions as an osmolyte. The concentration of MI is altered in many brain disorders including Alzheimer's disease and brain tumors. Currently available magnetic resonance spectroscopy (MRS) methods for measuring MI are limited to low spatial resolution. Here, we demonstrate that the hydroxyl protons on MI exhibit chemical exchange with bulk water and saturation of these protons leads to reduction in bulk water signal through a mechanism known as chemical exchange saturation transfer (CEST). The hydroxyl proton exchange rate (k=600s(-1)) is determined to be in the slow to intermediate exchange regime on the NMR time scale (chemical shift (Δω)>k), suggesting that the CEST effect of MI (MICEST) can be imaged at high fields such as 7T (Δω=1.2×10(3)rad/s) and 9.4T (Δω=1.6×10(3)rad/s). Using optimized imaging parameters, concentration dependent broad CEST asymmetry between ~0.2 and 1.5ppm with a peak at ~0.6ppm from bulk water was observed. Further, it is demonstrated that MICEST detection is feasible in the human brain at ultra high fields (7T) without exceeding the allowed limits on radiofrequency specific absorption rate. Results from healthy human volunteers (N=5) showed significantly higher (p=0.03) MICEST effect from white matter (5.2±0.5%) compared to gray matter (4.3±0.5%). The mean coefficient of variations for intra-subject MICEST contrast in WM and GM were 0.49 and 0.58 respectively. Potential overlap of CEST signals from other brain metabolites with the observed MICEST map is discussed. This noninvasive approach potentially opens the way to image MI in vivo and to monitor its alteration in many disease conditions. © 2010 Elsevier Inc.",,"Haris, M.;Cai, K.;Singh, A.;Hariharan, H.;Reddy, R.",2011,1,,0,
3993,Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex,"Iron deposition in the brain is a feature of normal aging, though in several neurodegenerative disorders, including Alzheimer's disease, the rate of iron accumulation is more advanced than in age-matched controls. Using laser ablation-inductively coupled plasma-mass spectrometry imaging we present here a pilot study that quantitatively assessed the iron content of white and gray matter in paraffin-embedded sections from the frontal cortex of Alzheimer's and control subjects. Using the phosphorus image as a confirmed proxy for the white/gray matter boundary, we found that increased intrusion of iron into gray matter occurs in the Alzheimer's brain compared to controls, which may be indicative of either a loss of iron homeostasis in this vulnerable brain region, or provide evidence of increased inflammatory processes as a response to chronic neurodegeneration. We also observed a trend of increasing iron within the white matter of the frontal cortex, potentially indicative of disrupted iron metabolism preceding loss of myelin integrity. Considering the known potential toxicity of excessive iron in the brain, our results provide supporting evidence for the continuous development of novel magnetic resonance imaging approaches for assessing white and gray matter iron accumulation in Alzheimer's disease.",,"Hare, D. J.;Raven, E. P.;Roberts, B. R.;Bogeski, M.;Portbury, S. D.;McLean, C. A.;Masters, C. L.;Connor, J. R.;Bush, A. I.;Crouch, P. J.;Doble, P. A.",2016,Aug 15,10.1016/j.neuroimage.2016.05.057,0,
3994,Neuroimaging of AIDS,"The increasing numbers of HIV-positive and AIDS cases, both in Indonesia and worldwide, have caused or will almost certainly be attended by an increase of positive results of imaging studies of the central nervous system (CNS). Whereas it is useless to do routine screening with cranial CT or MRI for asymptomatic HIV positive individuals, imaging modalities and especially MRI are very good in detecting, and monitoring the CNS abnormalities in symptomatic patients. Cerebral atrophy is the most common finding (40%), and is usually seen in subacute HIV encephalitis, and the AIDS dementia complex (ADC), as well as some of the opportunistic infections. Intracranial masses are most commonly caused by toxoplasmosis and lymphoma, and rarely by Kaposi’s sarcoma, tuberculoma, fungal and bacterial abscesses. Since early diagnosis of toxoplasmosis and appropriate therapy can significantly alter the course of the disease, differentiating this parasitic infection from lymphoma is crucial. This can be difficult since both entities share many imaging characteristics. An empirical anti-toxoplasmosis drug therapy trial is often helpful. White matter abnormalities are common in subacute HIV encephalitis, ADC and progressive multifocal leuco encephalopathy (PML). Leptomeningeal and ependymal changes are rare, but can arise in conjunction with some of the opportunistic infections and neoplasms. CT will detect many of the more extensive abnormalities, but MRI is better in most cases.",abscess;acquired immune deficiency syndrome;article;brain atrophy;brain lymphoma;central nervous system disease;cerebrovascular accident;computer assisted tomography;cryptococcal meningitis;cysticercosis;cytomegalovirus infection;disease course;herpes simplex encephalitis;HIV associated dementia;human;Human immunodeficiency virus infection;infectious encephalitis;intracranial tuberculoma;neuroimaging;nocardiosis;nuclear magnetic resonance imaging;parasitic meningitis;progressive multifocal leukoencephalopathy;toxoplasmosis;white matter,"Hardjasudarma, M.;Hardjasudarma, M.",1995,,10.13181/mji.v4i1.888,0,
3995,18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease,"Imaging of neurofibrillary pathology in the brain helps in diagnosing dementia, tracking disease progression, and evaluating the therapeutic efficacy of antidementia drugs. The radiotracers used in this imaging must be highly sensitive and specific for tau protein fibrils in the human brain. We developed a novel tau PET tracer, (18)F-THK5351, through compound optimization of arylquinoline derivatives. METHODS: The in vitro binding properties, pharmacokinetics, and safety of (18)F-THK5351 were investigated, and a clinical study on Alzheimer disease (AD) patients was performed. RESULTS: (18)F-THK5351 demonstrated higher binding affinity for hippocampal homogenates from AD brains and faster dissociation from white-matter tissue than did (18)F-THK5117. The THK5351 binding amount correlated with the amount of tau deposits in human brain samples. Autoradiography of brain sections revealed that THK5351 bound to neurofibrillary tangles selectively and with a higher signal-to-background ratio than did THK5117. THK5351 exhibited favorable pharmacokinetics and no defluorination in mice. In first-in-human PET studies in AD patients, (18)F-THK5351 demonstrated faster kinetics, higher contrast, and lower retention in subcortical white matter than(18)F-THK5117. CONCLUSION: (18)F-THK5351 is a useful PET tracer for the early detection of neurofibrillary pathology in AD patients.",,"Harada, R.;Okamura, N.;Furumoto, S.;Furukawa, K.;Ishiki, A.;Tomita, N.;Tago, T.;Hiraoka, K.;Watanuki, S.;Shidahara, M.;Miyake, M.;Ishikawa, Y.;Matsuda, R.;Inami, A.;Yoshikawa, T.;Funaki, Y.;Iwata, R.;Tashiro, M.;Yanai, K.;Arai, H.;Kudo, Y.",2016,Feb,10.2967/jnumed.115.164848,0,
3996,Cerebral microbleeds in Binswanger's disease: a gradient-echo T2*-weighted magnetic resonance imaging study,"We investigated the incidence and the number of microbleeds (MBs) on T2*-weighted gradient-echo magnetic resonance imaging in 30 Binswanger's disease (BD) patients with diffuse white matter lesions and a varying degree of lacunar infarction, 51 multiple lacunar stroke (MLS) patients with multiple lacunar infarction and no or mild white matter lesions, and 59 elderly controls. MBs were found in 23 (77%) patients with BD, 26 (51%) patients with MLS, and 5 (8%) controls, and the incidence and the number of MBs were significantly greater in the BD group compared with MLS and control groups. Patients with BD had a more widespread location of MBs. More specifically, MBs were commonly found in areas within or surrounded by white matter lesions of the patients with BD. When 81 patients from both the BD and MLS groups were analyzed, logistic regression analysis showed that number of lacunar infarct, severity of white matter hyperintensity, and use of antiplatelet agents were significantly associated with MBs. Patients with BD exhibited a high frequency and number of MBs, indicating advanced bleeding-prone microangiopathy within the brain, which should be taken into account in treatment and management.","Aged;Aged, 80 and over;Analysis of Variance;Brain/ pathology;Brain Infarction/pathology;Cerebral Hemorrhage/ pathology;Chi-Square Distribution;Dementia, Vascular/ pathology;Echo-Planar Imaging/ methods;Female;Humans;Logistic Models;Male;Microcirculation/pathology","Hanyu, H.;Tanaka, Y.;Shimizu, S.;Takasaki, M.;Fujita, H.;Kaneko, N.;Yamamoto, Y.;Harada, M.",2003,Apr 17,,0,
3997,Cerebral microbleeds in Alzheimer's disease [3],,Alzheimer disease;brain hemorrhage;clinical trial;human;letter;microangiopathy;nuclear magnetic resonance imaging;priority journal;white matter,"Hanyu, H.;Tanaka, Y.;Shimizu, S.;Takasaki, M.;Abe, K.",2003,,,0,
3998,Cerebral microbleeds in Alzheimer's disease,,"Aged;Aged, 80 and over;Alzheimer Disease/*complications/pathology;Brain/pathology/radiography;Cerebral Hemorrhage/*etiology;Female;Humans;Magnetic Resonance Imaging;Male","Hanyu, H.;Tanaka, Y.;Shimizu, S.;Takasaki, M.;Abe, K.",2003,Dec,10.1007/s00415-003-0245-7,0,
3999,Diffusional anisotropy in the cerebral white matter in Alzheimer-type dementia,"To investigate changes in water diffusion in the cerebral white matter in Alzheimer-type dementia (AD), diffusion MRI studies were performed on 11 patients with AD without hyperintensity lesions on T2-weighted images, and 10 age-matched controls. In the anterior and posterior white matter around the lateral ventricule, and the splenium of the corpus callosum, the apparent diffusion coefficients (ADCs), in which the diffusion gradient was applied perpendicular to the predominant fiber direction, were significantly higher in patients with AD than in the controls. However, those in which the diffusion gradient was applied parallel to the predominant fiber direction, there were no significant difference in ADCs between patients and controls. Therefore, diffusional anisotropy was lost in the white matter. These results suggest that demyelination occurs in patients with AD even in apparently normal white matter (without signal abnormalitis). Degeneration related to grey matter encephalopathy may be a possible explanation of the demyelinating process in the white matter.",Alzheimer Disease/ metabolism;Brain/ metabolism;Diffusion;Female;Humans;Magnetic Resonance Imaging;Male,"Hanyu, H.;Shindo, H.;Kakizaki, D.;Abe, K.;Takasaki, M.",1996,Jul,,0,
4000,Increased water diffusion in cerebral white matter in Alzheimer's disease,"We investigated the changes in water diffusion in the cerebral white matter in 19 patients with Alzheimer's disease (AD), including 11 without and 8 with periventricular hyperintensity (PVH) lesions, using diffusion-weighted magnetic resonance imaging (MRI). The apparent diffusion coefficients in the anterior and posterior white matter were significantly higher in the 19 AD patients than in the 10 age-matched controls. The apparent diffusion coefficients were higher in patients with PVH than in those without. The anisotropic ratios, defined as diffusion restricted perpendicular to the direction of the nerve fibers, were significantly higher in AD patients, even in those without PVH, than in the controls. Our results suggest that mild myelin loss occurs in AD patients even in the apparently normal white matter. A definite loss of myelin and axons, including incomplete infarction, occurs in the white matter, as seen on T2-weighted images as PVH. Studies with diffusion-weighted MRI may allow the characterization of different pathological processes and enable the demonstration of underlying white matter lesions in AD that cannot be visualized by conventional MRI.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ metabolism;Cerebral Cortex/ cytology/metabolism;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers/ metabolism;Water/ metabolism","Hanyu, H.;Shindo, H.;Kakizaki, D.;Abe, K.;Iwamoto, T.;Takasaki, M.",1997,,,0,
4001,[Diffusion MRI study of cerebral white matter lesions in patients with Binswanger's disease],"We performed diffusion MRI studies in 14 patients with extensive ischemic leukoencephalopathy, including 9 with dementia (diagnosed as Binswanger's disease), and 5 without dementia, and 8 age-matched controls. Apparent diffusion coefficients (ADCs) in anterior and posterior periventricular white matter were significantly higher in demented and non-demented patients than in the controls, and diffusion anisotropy disappeared in patients because of the high ratio of the diffusion coefficients perpendicular to the nerve fibers to those parallel to the nerve fibers. ADCs in the corpus callosum were significantly higher in demented patients that in non-demented patients and controls. Therefore, diffusion anisotropy disappeared only in demented (Binswanger's disease) patients. These results suggest that the cerebral white matter lesions in Binswanger's disease reflect a decrease of nerve fibers and diffuse myelin loss, and that the loss of nerve fibers in the corpus callosum may play a role in inducing cognitive decline. Diffusion MRI may be useful in the pathophysiological evaluation of cerebral white matter lesions.","Aged;Aged, 80 and over;Brain/*pathology;Dementia, Vascular/*diagnosis;Female;Humans;Magnetic Resonance Imaging/methods;Male;Nerve Tissue/*pathology","Hanyu, H.;Shindo, H.;Kakizaki, D.;Abe, K.;Iwamoto, T.;Takasaki, M.",1996,Mar,,0,
4002,Differences in regional cerebral blood flow patterns in male versus female patients with Alzheimer disease,"BACKGROUND AND PURPOSE: There may be some differences in the pathophysiology between men and women with Alzheimer disease (AD). This study was undertaken to explore the possible influence of sex on regional cerebral blood flow (rCBF) patterns in patients with AD. METHODS: Single photon emission CT (SPECT) was performed in 30 men and 30 women with AD, and the SPECT data were analyzed by using 3D stereotactic surface projections. RESULTS: There were no significant differences in age, duration of disease, years of education, cognitive deficits and patterns, and MR imaging findings (grade of brain atrophy and extent of white matter hyperintensity lesions) between the two groups. Both male and female patient groups showed decreased rCBF patterns in the parietotemporal lobe, posterior cingulate cortex, and precuneus, which are considered to be the characteristic SPECT findings of AD. There were, however, some differences in rCBF patterns: men had a more severe decrease of rCBF in the parietal and posterior cingulate cortex, whereas women had a more severe decrease of rCBF in the medial temporal region and frontal lobe. CONCLUSION: These data provide evidence that patterns of rCBF deficits differ between the sexes, a finding that supports the concept of heterogeneity of the underlying pathophysiology of AD.","Aged;Aged, 80 and over;Alzheimer Disease/physiopathology/ radionuclide imaging;Cerebral Cortex/ blood supply/radionuclide imaging;Female;Frontal Lobe/blood supply/radionuclide imaging;Gyrus Cinguli/blood supply/radionuclide imaging;Humans;Image Processing, Computer-Assisted;Imaging, Three-Dimensional;Male;Mental Status Schedule;Middle Aged;Parietal Lobe/blood supply/radionuclide imaging;Reference Values;Regional Blood Flow/physiology;Sex Factors;Temporal Lobe/blood supply/radionuclide imaging;Tomography, Emission-Computed, Single-Photon","Hanyu, H.;Shimizu, S.;Tanaka, Y.;Takasaki, M.;Koizumi, K.;Abe, K.",2004,Aug,,0,
4003,Differences in magnetization transfer ratios of the hippocampus between dementia with Lewy bodies and Alzheimer's disease,"We compared magnetization transfer ratios (MTRs) in the brains of patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) to determine whether regional differences in the brain structures between DLB and AD are detectable with magnetization transfer imaging. Seventeen patients with DLB, 31 patients with AD and 18 elderly normal controls were included. Although no significant differences were found in MTRs in the frontal white matter between the three groups, MTRs in the hippocampus, parahippocampus, and posterior cingulate white matter in both patients with DLB and AD were significantly lower than those in age-matched control subjects. However, MTRs in the hippocampus of patients with DLB were significantly higher than those in patients with AD. Logistic regression analysis revealed that hippocampal MTR yielded a sensitivity of 76% and a specificity of 71% in discriminating DLB from AD. These results may reflect underlying histopathological differences with less severe neuronal degeneration in the hippocampus of DLB. MTR measurement of the hippocampus may contribute to the clinical differentiation between DLB and AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain Mapping;Female;Hippocampus/ pathology;Humans;Lewy Body Disease/ pathology;Logistic Models;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests;Reference Values","Hanyu, H.;Shimizu, S.;Tanaka, Y.;Kanetaka, H.;Iwamoto, T.;Abe, K.",2005,May 20-27,10.1016/j.neulet.2005.01.088,0,
4004,Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease,"We investigated the changes in water diffusion in the hippocampus and the temporal white matter (the temporal stem) in eight patients with possible Alzheimer's disease (AD), 10 patients with probable AD, and 10 age-matched controls, using coronal diffusion-weighted magnetic resonance (MR) imaging. Apparent diffusion coefficients (ADCs) were derived for the three orthogonal axes and an index of diffusion anisotropy (IDA = ADC(max-min)/ADC(mean)) was then calculated. Although no significant differences were found in ADC and IDA values in the hippocampal body between controls and patients, vertical (superior-inferior) ADC values and ADC(mean) values in the temporal stem of patients with AD were significantly higher than those in controls, and IDA values were therefore significantly lower in patients with possible or probable AD than those in controls. Moreover, IDA values in the temporal stem were significantly correlated with the clinical severity. These results suggest that decreased fiber density, such as the disruption and loss of axonal membranes or myelin, occur early in the temporal stem, probably due to secondary degeneration related to grey matter pathology including the medial temporal lobe.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Diffusion;Female;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Temporal Lobe/ pathology","Hanyu, H.;Sakurai, H.;Iwamoto, T.;Takasaki, M.;Shindo, H.;Abe, K.",1998,Apr 1,,0,
4005,Differential diagnosis of Alzheimer type dementia and vascular dementia based on neuroimaging study,"A new method for differential diagnosis of Alzheimer type dementia (AD) and vascular dementia (VD) based on neuroimaging studies was developed by Hayashi's quantification theory II. Fifty five patients with AD and 36 patients with VD underwent both SPECT and MRI studies. Both images in each subject were scored according to the extent of hypoperfusion in areas including frontal and temporoparietal regions and the severity of deep white matter lesions and medial temporal lobe atrophy. The scores of AD and VD patients were significantly different, and this difference was considered to contribute most to the differential diagnosis of AD and VD. The weight of each score of SPECT and MRI items was computed, and the sum of the weights was calculated as a score for each subject to host distinguish AD from VD patients. This method was designed to simplify the calculation of the sample scores, and the sum of the weights was established so that a positive score (0≤) indicated the probability of AD, while a negative score (<0) indicated the probability of VD. The correct diagnosis rate was 91% (50/55) for AD and 89% (32/36) for VD, for an overall discrimination of 90%. The present method seemed to be practically useful in the differential diagnosis of AD and VD.",adult;aged;Alzheimer disease;article;brain atrophy;brain perfusion;controlled study;diagnostic imaging;differential diagnosis;female;human;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance imaging;single photon emission computer tomography;temporal lobe;white matter,"Hanyu, H.;Nakano, S.;Abe, S.;Arai, H.;Iwamoto, T.;Takasaki, M.",1995,,,0,4006
4006,[Differential diagnosis of Alzheimer-type dementia and vascular dementia based on neuroimaging study],"A new method for differential diagnosis of Alzheimer-type dementia (AD) and vascular dementia (VD) based on neuroimaging studies was developed by Hayashi's quantification theory II. Fifty-five patients with AD and 36 patients with VD underwent both SPECT and MRI studies. Both images in each subject were scored according to the extent of hypoperfusion in areas including frontal and temporoparietal regions and the severity of deep white matter lesions and medial temporal lobe atrophy. The scores of AD and VD patients were significantly different, and this difference was considered to contribute most to the differential diagnosis of AD and VD. The weight of each score of SPECT and MRI items was computed, and the sum of the weights was calculated as a score for each subject to best distinguish AD from VD patients. This method was designed to simplify the calculation of the sample scores, and the sum of the weights was established so that a positive score (0 < or =) indicated the probability of AD, while a negative score (< 0) indicated the probability of VD. The correct diagnosis rate was 91% (50/55) for AD and 89% (32/36) for VD, for an overall discrimination of 90%. The present method seemed to be practically useful in the differential diagnosis of AD and VD.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/radionuclide imaging;Brain/pathology;Cerebrovascular Circulation;Dementia, Vascular/*diagnosis/radionuclide imaging;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Tomography, Emission-Computed, Single-Photon","Hanyu, H.;Nakano, S.;Abe, S.;Arai, H.;Iwamoto, T.;Takasaki, M.",1995,Jul,,0,
4007,Differences of neuroimaging between early-onset and late-onset Alzheimer-type dementia,"Several studies have shown that the symptomatology and the neuropathological and neurochemical changes of early-onset Alzheimer's disease (EAD) differ from those of late-onset Alzheimer's disease (LAD). The aim of the present study is to examine differences in SPECT and MRI findings between EAD and LAD. Cerebral blood flow and patterns on SPECT, and deep white matter lesions and cerebral atrophy on MRI in 17 patients with EAD were compared with 30 patients with LAD without cerebrovascular risk factors. Temporoparietal activity ratio, divided by cerebellum, on SPECT imaging in patients with EAD was significantly lower than in patients with LAD. In a qualitative assessment of perfusion patterns, bilateral temporoparietal hypoperfusion, which is typical in AD, was seen more frequently in patients with EAD than in those with LAD. Among white matter changes in MRI, the score of white matter hyperintensity was significantly higher in LAD than in EAD patients. However, there was no significant difference between periventricular hyperintensity scores. Though ventricular enlargement did not differ significantly in EAD and LAD, cortical atrophy scores in LAD were significantly higher than in EAD. Cortical atrophy scores were significantly higher in patients with atypical perfusion patterns on SPECT, (e.g. global hypoperfusion in addition to temporoparietal change), than in patients with typical perfusion pattern. These results indicate that functional and morphological imagings in LAD differ with those in EAD, probably due to less-prominent neuropathological degeneration combined with age-related alterations.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/radionuclide imaging;Brain/ pathology/radionuclide imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, Emission-Computed, Single-Photon","Hanyu, H.;Nakano, S.;Abe, S.;Arai, H.;Iwamoto, T.;Takasaki, M.",1995,Oct,,0,
4008,Use of MRI in the diagnosis of dementia of the Alzheimer type,"MRI of 31 patients with dementia of the Alzheimer type (DAT) (mean age 74.7 years) were studied to detect characteristic findings, and compared with those of 24 normal elderly controls (mean age 74.1 years). Atrophy was quantitated by planimetric and linear measurements, and periventricular and deep white matter signal abnormalities were assessed by subjective ratings. Although we observed significant differences between the DAT patients and controls, there was overlap in each of the measurements. Of these, the ratio of the temporal horn area and the pattern of linear measurements (the width of the temporal horn body - the medial temporal lobe width - the interuncal distance) best distinguished the DAT patients from controls. Twenty-five patients (81%) had a ratio of the temporal horn area larger than the value of the mean + 2SD of the controls. AV-shaped pattern, in which the medial temporal lobe width was smaller than the other two values, was demonstrated in 84% of the patients and only 8% of the controls. Although signal abnormalities were not useful for diagnostic purposes, periventricular hyperintensities were more commonly seen in the DAT patients than in the controls, and correlated with cognitive function. MRI studies suggest that the assessment of medial temporal lobe atrophy is useful in the diagnosis of DAT, and periventricular hyperintensity may be related in some way to the disease process.",aged;Alzheimer disease;article;brain atrophy;clinical article;clinical trial;controlled clinical trial;controlled study;human;nuclear magnetic resonance imaging,"Hanyu, H.;Nakano, S.;Abe, S.;Arai, H.;Iwamoto, T.;Takasaki, M.",1994,,,0,
4009,Diffusional anisotropy in cerebral white matter in patients with dementia,"We studied changes in water diffusion in cerebral white matter in 10 patients with Binswanger's disease (BD), 8 patients with Alzheimer's disease (AD) who had periventricular hyperintensity lesions on T2-weighted images, and 8 age-matched controls. The apparent diffusion coefficients measured in the anterior and posterior white matter were significantly higher in the patients than in the controls, but there was no significant difference between patients with BD and those with AD. The anisotropy ratios, difined as diffusion perpendicular to the nerve fiber direction, were higher in the patients than in the controls. The anisotropy ratio in the anterior white matter was significantly higher in patients with BD than in those with AD, while in the posterior white matter the ratio was significantly higher in patients with AD than in those with BD. These results suggest that in BD and AD cerebral white matter lesions such as periventricular hyperintensity lesions reflect a loss of myelin and axons, and that loss of myelin occurs preferentially in the anterior white matter in BD and in the posterior white matter in AD.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Anisotropy;Brain/ pathology;Dementia/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Hanyu, H.;Iwamoto, T.;Takasaki, M.;Shindo, H.;Kakizaki, D.;Abe, K.",1996,Oct,,0,
4010,Regional differences in diffusion abnormality in cerebral white matter lesions in patients with vascular dementia of the Binswanger type and Alzheimer's disease,"We investigated changes in water diffusion in the cerebral white matter of 14 patients with vascular dementia of the Binswanger type (VDBT) and ten patients with Alzheimer's disease (AD) with periventricular hyperintensity (PVH) lesions using diffusion-weighted magnetic resonance imaging (MRI) and studied the pathophysiological differences between white matter lesions found in these two conditions. Apparent diffusion coefficients (ADCs) in the anterior and posterior white matter and the genu and splenium of the corpus callosum were significantly higher in both groups of patients than in the 12 age-matched controls, and ADC values in VDBT and AD groups were almost the same. ADC ratios, defined as diffusion restricted perpendicular to the direction of nerve fibers, were also significantly higher in the patients than in the control subjects. However, there were regional differences in ADC ratios in the two conditions, with ratios in VDBT being higher in the anterior portions of the white matter but ratios in AD were higher in the posterior portions. The diffusion-weighted MRI technique may be useful in the differential diagnosis of VDBT and AD with white matter lesions.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Cerebral Cortex/ pathology;Corpus Callosum/pathology;Dementia, Vascular/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology","Hanyu, H.;Imon, Y.;Sakurai, H.;Iwamoto, T.;Takasaki, M.;Shindo, H.;Kakizaki, D.;Abe, K.",1999,Mar,,0,
4011,Magnetization transfer imaging of periventricular white matter lesions in patients with multi-infarct dementia,"Using magnetization transfer (MT) imaging, we studied the underlying pathological conditions of periventricular hyperintense (PVH) white matter changes seen on T2-weighted MR images of patients with multi-infarct dementia. Twenty-two patients with multiple lacunar infarcts and PVH lesions, including 11 with dementia (diagnosed as multi-infarct dementia) and 11 without dementia, and 10 control subjects (with multiple lacunes, but no PVH lesion) were studied using the MT technique. MT ratios (MTRs) were calculated for PVH lesions (normal-appearing frontal white matter in controls) and the genu of the corpus callosum. Signal intensities on T2-weighted images in PVH lesions of patients were significantly higher than those in normal-appearing white matter of controls, while there were no significant differences in signal intensity in the genu of the corpus callosum among the dementia, non-dementia and control groups. However, MTRs in patients with PVH lesions were significantly lower than those in controls, and MTRs in demented patients were significantly lower than those in non-demented patients. Moreover, MTRs in the genu of the corpus callosum of demented patients were significantly lower than in those in non-demented patients and controls. MTRs in PVH lesions and the genu of the corpus callosum significantly correlated with Hasegawa's dementia scale score. These results suggest that there is some difference in histopathologic changes of PVH lesions between demented and non-demented patients and that the pathological substrate in the corpus callosum may play a role in inducing cognitive decline. Studies with MT imaging may allow the characterization of different pathological conditions that cannot be visualized by conventional MRI.","Aged;Aged, 80 and over;Brain/ pathology;Corpus Callosum/pathology;Dementia, Multi-Infarct/ diagnosis;Female;Humans;Magnetic Resonance Imaging/ methods;Male","Hanyu, H.;Imon, Y.;Asano, T.;Iwamoto, T.;Takasaki, M.",1998,May,,0,
4012,Increased blood-brain barrier permeability in white matter lesions of Binswanger's disease evaluated by contrast-enhanced MRI,"We investigated blood-brain barrier (BBB) permeability in white matter lesions of Binswanger's disease (BD) with contrast-enhanced MRI. Three subject groups were studied: 17 patients with BD and periventricular hyperintensities (PVH) on MRI, 10 patients with ischemic cerebrovascular events and with PVH but no dementia, and 14 age-matched control subjects without PVH. BBB permeability was quantified by calculation of T(1) change defined as [(T(1post) - T(1pre))/T(1pre)] x100, where T(1pre) and T(1post) represent the T(1) relaxation times before and after Gd-DTPA administration. T(1) change in PVH of BD patients significantly decreased in comparison with that observed in PVH of the nondemented patients and in normal white matter of the control subjects, but no significant T(1) change was observed between the PVH of the nondemented patients and normal white matter of the controls. There was a significant correlation between the Mini-Mental State Examination score and T(1) change for areas of PVH in BD. These results suggest that BBB permeability increases in areas of PVH in BD and that a BBB dysfunction is related to a progression of cognitive impairment.","Aged;Aged, 80 and over;*Blood-Brain Barrier;Brain/*metabolism/pathology;Capillary Permeability;Dementia, Vascular/*diagnosis/metabolism;Female;Gadolinium DTPA/pharmacokinetics;Humans;Image Enhancement;Magnetic Resonance Imaging;Male","Hanyu, H.;Asano, T.;Tanaka, Y.;Iwamoto, T.;Takasaki, M.;Abe, K.",2002,,58326,0,
4013,Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson's disease with and without dementia and in progressive supranuclear palsy,"We measured the magnetisation transfer ratio (MTR) in the subcortical grey and white matter of 11 patients with idiopathic Parkinson's disease (PD) without dementia, six with PD with dementia (PDD), six with progressive supranuclear palsy (PSP), and 12 elderly control subjects to assess regional differences in structural brain damage. There were no significant differences in MTR in any region between PD and controls. However, patients with PDD had significantly lower MTR in the subcortical white matter, including the frontal white matter and the genu of the corpus callosum than the controls, whereas PSP had significantly lower MTR in the subcortical grey matter, including the putamen, globus pallidus and thalamus, in addition to the subcortical white matter. This suggests that regional patterns of structural brain damage can be detected using the magnetisation transfer technique. Measurement of MTR in the subcortical grey and white matter may be useful in differential diagnosis.","Aged;Analysis of Variance;Corpus Striatum/*pathology;Dementia/diagnosis/pathology;Diagnosis, Differential;Female;Humans;Image Interpretation, Computer-Assisted/*methods;Magnetic Resonance Imaging/*methods;Male;Parkinson Disease/diagnosis/*pathology;Supranuclear Palsy, Progressive/diagnosis/pathology","Hanyu, H.;Asano, T.;Sakurai, H.;Takasaki, M.;Shindo, H.;Abe, K.",2001,Jul,,0,
4014,Magnetization transfer ratio in cerebral white matter lesions of Binswanger's disease,"We measured the magnetization transfer (MT) ratios in white matter lesions of Binswanger's disease (BD) and compared them with BD and with similar-appearing changes in non-demented elderly subjects and cerebral infarction. Four subject groups were studied: 30 patients with BD and periventricular hyperintensity (PVH) on MRI, 29 patients with ischemic cerebrovascular event with PVH but no dementia, 17 patients with old cerebral infarction, and 26 elderly control subjects. MT ratios were calculated for areas of PVH in BD and non-demented subjects, of infarction, and of normal-appearing white matter in controls. The decrease in MT ratios for areas in PVH of non-demented subjects and BD and in infarction compared with normal white matter in controls was 12, 20, and 35%, respectively. The MT ratio in PVH of BD was significantly lower than that in PVH of non-demented subjects, but not to the levels seen in areas of infarction. There was a significant high correlation between the Mini-Mental State Examination score and MT ratio for area of PVH (r = 0.790). MT ratio distinguishes PVH in BD patients from those in non-demented subjects, suggesting underlying histopathological differences. Tissue damage in white matter lesions of BD may be more severe than that in non-demented subjects, but not as much as with complete infarction.","Aged;Aged, 80 and over;Analysis of Variance;Brain/pathology;Cerebral Infarction/*diagnosis;Dementia, Vascular/*diagnosis;Diffuse Cerebral Sclerosis of Schilder/*diagnosis;Female;Humans;Intelligence Tests;Magnetic Resonance Imaging;Male","Hanyu, H.;Asano, T.;Sakurai, H.;Iwamoto, T.;Takasaki, M.;Shindo, H.;Abe, K.",1999,Jul 1,,0,
4015,[Relation between hippocampal damage and cerebral cortical function in Alzheimer's disease],"We investigated the relation between hippocampal damage and cerebral cortical dysfunction in Alzheimer's disease (AD) using MRI and SPECT. Nineteen patients with AD and 10 control subjects were studied. Hippocampal damage (including hippocampal formation, entorhinal cortex, and parahippocampal white matter) was assessed to evaluate the severity of atrophy and the magnetization transfer ratio (MTR) and cerebral cortical dysfunction was evaluated by quantitative cerebral blood flow (CBF) measurements using SPECT with 99mTc-ECD. Compared with controls, patients with AD had significantly more atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus and parahippocampus. There were significant correlations between the severity of hippocampal damage and regional CBF in temporoparietal lobes. Mini-Mental State Examination scores significantly correlated with the severity of hippocampal damage and regional CBFs in temporoparietal lobes. These results suggest that the functional effect of hippocampal damage occurs in temporoparietal lobes in AD, probably due to neuronal disconnections between hippocampal areas (including the entorhinal cortex) and temporoparietal lobes.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/*physiopathology;Atrophy;Cerebral Cortex/pathology/*physiopathology/radionuclide imaging;Cerebrovascular Circulation;Female;Hippocampus/*pathology/radionuclide imaging;Humans;Magnetic Resonance Imaging;Male;Tomography, Emission-Computed, Single-Photon","Hanyu, H.;Asano, T.;Kogure, D.;Sakurai, H.;Iwamoto, T.;Takasaki, M.",2000,Nov,,0,
4016,[Contributing factors to intellectual impairment in patients with multiple lacunar infarctions],"The author investigated factors leading to intellectual impairment in patients with multiple lacunar infarctions. The subjects consisted of 40 patients with multi-infarct dementia (MID) and 17 nondemented patients with multiple infarctions (MI) who showed multiple lacunar infarctions in the deep penetrating arterial territory on CT. MID patients showed more marked and extensive periventricular lucency (PVL), a higher degree of ventricular index (VI) measured on CT, and were of a higher age, and had poorer activity of daily living (ADL) compared with MI patients. There were significant correlations between the PVL score, VI, ADL score, age and Hasegawa's dementia rating score (HDS). However, no significant differences in sex, site of infarct, and the count of low density areas reflected lacunar infarction on CT, and vascular risk factors were shown between MID and MI patients. Multiple regression analysis demonstrated that the PVL score and VI showed the highest partial correlations for HDS, and that the ADL score and age were also independently contributing factors. Our results suggest that deep white matter lesions observed as PVL on CT and ventricular enlargement were the most important factors contributing to intellectual impairment in patients with multiple lacunar infarcts, and that physical factors such as ADL and age can be considered to be related to the development of dementia.","Activities of Daily Living;Aged;Aged, 80 and over;Aging;Brain/pathology;Dementia, Multi-Infarct/physiopathology/*psychology;Female;Humans;Male;Middle Aged;Regression Analysis","Hanyu, H.;Abe, S.;Arai, H.;Kubo, H.;Shimizu, N.;Iwamoto, T.;Takasaki, M.;Fujita, R.;Tomori, C.;Motegi, A.",1992,Apr,,0,
4017,Dilated perivascular spaces in the Basal Ganglia are a biomarker of small-vessel disease in a very elderly population with dementia,"BACKGROUND AND PURPOSE: Dilated perivascular spaces have been shown to be a specific biomarker of cerebral small-vessel disease in young patients with dementia. Our aim was to examine the discriminative power of dilated cerebral perivascular spaces as biomarkers of small-vessel disease in a very elderly population of patients with dementia. MATERIALS AND METHODS: We studied healthy volunteers (n = 65; mean age, 78 +/- 5.6 years) and subjects with vascular dementia (n = 39; mean age, 76.9 +/- 7.7 years) and Alzheimer disease (n = 47; mean age, 74.1 +/- 8.5 years). We compared white matter hyperintensity and 2 semiquantitative perivascular space scoring systems (perivascular space-1 and perivascular space-2). Intra- and interobserver agreement was assessed by using a weighted Cohen kappa statistic. Multinomial regression modeling was used to assess the discriminative power of imaging features to distinguish clinical groups. RESULTS: White matter hyperintensity scores were higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .01). The perivascular space-1 score was higher in vascular dementia and Alzheimer disease than in healthy volunteers (P < .01). The perivascular space-2 score in the centrum semiovale showed no intergroup differences. However, perivascular space-2 in the basal ganglia was higher in vascular dementia than in Alzheimer disease (P < .05) or healthy volunteers (P < .001) and higher in Alzheimer disease than in healthy volunteers (P < .001). Modeling of dementia versus healthy volunteers, Alzheimer disease versus healthy volunteers, and vascular dementia against Alzheimer disease demonstrated perivascular space-2basal ganglia as the only imaging parameter with independent significant discriminative power (P < .01, P < .01, and P < .05) with areas under the receiver operating characteristic curve of 0.855, 0.774, and 0.71, respectively. Modeling of vascular dementia versus healthy volunteers showed that perivascular space-2basal ganglia (P < .01) and the modified Scheltens score (P < .05) contributed significant, independent discriminatory power, accounting for 34% and 13% of the variance in the model respectively. CONCLUSIONS: Dilated perivascular spaces remain a valuable biomarker of small-vessel disease in an elderly population.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Basal Ganglia/ pathology;Dementia, Vascular/ pathology;Female;Humans;Magnetic Resonance Imaging;Male","Hansen, T. P.;Cain, J.;Thomas, O.;Jackson, A.",2015,May,10.3174/ajnr.A4237,0,
4018,Neuropathy in adult metachromatic leukodystrophy,"Metachromatic leukodystrophy is a rare autosomal recessive disorder with deficient arylsulphatase A activity. Different forms occur according to the age at onset of symptoms. Adult forms generally present with presenile dementia and/or psychiatric symptoms. We report a case of a 45-year-old woman, without a family history of neuropsychiatric disorders, presenting with complaints of numbness and weakness of the lower limbs. No intellectual or behavioral disturbances were clinically detectable. Electrophysiological investigation was compatible with severe demyelinating neuropathy in upper and lower limbs. MRI of the brain showed multiple white matter lesions. Adult metachromatic leukodystrophy was diagnosed on the basis of low leucocyte arylsulfatase-A-activity and accumulation of metachromatic material in the sural nerve. Pseudo-deficiency was excluded by DNA analysis. This case indicates that adult metachromatic leukodystrophy should be considered in patients with symptoms and signs resembling multiple sclerosis with peripheral neuropathy and in patients with neuropathy of unknown etiology.",article;brain disease;case report;differential diagnosis;female;human;mental disease;metachromatic leukodystrophy;middle aged;nuclear magnetic resonance imaging;peripheral neuropathy;psychological aspect,"Hansen, L. M.;Kristensen, O.;Friis, M. L.",1994,,,0,
4019,Widespread argentophilic structures in progressive supranuclear palsy. An autopsy case report,"We report an autopsy case of progressive supranuclear palsy (PSP) with a five-year clinical course. A 67-year-old man was suffering from a gait disturbance and mental deterioration. Neurological examination at the age of 71 revealed pseudobulbar palsy, horizontal ophthalmoplegia, and trunkal dystonia, and a diagnosis of PSP was made. Mental deterioration including forgetfulness and character change was also noted, and the patient sometimes exhibited intermittent stuporous states. Cranial computed tomography and magnetic resonance images revealed moderate brain atrophy, predominantly in the frontal lobes. The patient died of bronchopneumonia at the age of 71. Neuropathological examination confirmed typical pathological changes of PSP, such as neuronal loss, neurofibrillary tangles, and fibrillary gliosis in the subcortical nuclei. Gallyas-Braak silver impregnation revealed neurofibrillary tangles, silver-positive glia and thread-like structures in degenerating subcortical nuclei. In addition to these classical lesions, the argentophilic structures were detected in the cerebral cortex, cortical white matter and cerebellar white matter. In the cerebral cortex, they were abundant mostly in the precentral gyrus and subcortical white matter. Immunohistochemical studies revealed that most silver-positive structures were also tau 2 antibody-positive. Thus, these argentophilic structures seemed to be closely related to abnormal tau protein. Their distribution in this case implies that lesions related to abnormal tau protein may occur more extensively in the brains of PSP than expected.",,"Hanihara, T.;Kubota, H.;Amano, N.;Yamaoka, K.;Yagishita, S.",1994,1994,,0,
4020,Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson's disease longitudinally,"Previous studies have shown greater atrophy in grey and white matter of various brain regions in patients with Parkinson's disease with mild cognitive impairment than in those without. These anatomical differences likely account for the distinct clinical profiles observed between those groups, but do not account for the evolution of regional brain degradation observed as the disease evolves. Although we have shown recently that cortical thinning correlates significantly more with disease duration in Parkinson's patients with mild cognitive impairment than in those without, to the best of our knowledge no study to date has explored this longitudinally. The present study investigated the longitudinal changes of the cortical and subcortical grey matter in patients with Parkinson's disease with and without mild cognitive impairment. Additionally, these two groups were compared with healthy controls. We found a higher rate of cortical thinning in the temporal, occipital, parietal and supplementary motor area, in patients with Parkinson's disease with mild cognitive impairment compared with both cognitively stable patients and healthy controls. On the other hand cognitively stable patients had only one lateral occipital and one fusiform cluster with increased rate of thinning compared with healthy individuals. Correlating the rate of change of cortical thickness with the results of Montreal Cognitive Assessment scores revealed significant thinning associated with cognitive decline in the group of all patients, in similar regions including temporal and medial occipital lobe. Finally, a significant decrease in the volume of the amygdala and nucleus accumbens was observed specifically in patients with Parkinson's disease with mild cognitive impairment. These results indicate that the early presence of mild cognitive impairment in patients with Parkinson's disease is associated with a faster rate of grey matter thinning in various cortical regions as well as a significant diminishment of limbic subcortical structures. This specific pattern of brain degradation associated with the early presence of mild cognitive impairment might serve as a marker of development toward dementia. © 2013 The Author.",catechol methyltransferase inhibitor;dopamine receptor stimulating agent;levodopa;monoamine oxidase B inhibitor;adult;amygdaloid nucleus;article;brain cortex;brain cortex atrophy;clinical article;controlled study;cortical thickness (brain);disease duration;executive function;female;gray matter;human;inferior frontal gyrus;learning;left hemisphere;male;middle aged;mild cognitive impairment;nuclear magnetic resonance imaging;nucleus accumbens;nucleus raphe pallidus;Parkinson disease;priority journal;right hemisphere;supplementary motor area;temporal gyrus;Unified Parkinson Disease Rating Scale;Wechsler memory scale,"Hanganu, A.;Bedetti, C.;Degroot, C.;Mejia-Constain, B.;Lafontaine, A. L.;Soland, V.;Chouinard, S.;Bruneau, M. A.;Mellah, S.;Belleville, S.;Monchi, O.",2014,,,0,
4021,Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer's disease,"AIM: The aim of the present study was to evaluate the relationship between baseline white matter lesions (WML) and changes in regional cerebral blood flow during longitudinal follow up of patients with Alzheimer's disease (AD). METHODS: A total of 38 patients with AD were included in the study (16 men, 22 women; mean age 77.8 years). All patients were evaluated using the Mini-Mental State Examination and brain perfusion single-photon emission computed tomography at baseline with an approximately 2-year follow up. The patients were divided into two subgroups according to the presence of WML on magnetic resonance imaging. Single-photon emission computed tomography data were analyzed using a voxel-by-voxel group analysis with Statistical Parametric Mapping 8 and region of interest analysis using FineSRT. Changes in Mini-Mental State Examination scores and regional cerebral blood flow were analyzed using the Wilcoxon signed-rank test. RESULTS: Mean Mini-Mental State Examination scores in AD patients with WML significantly decreased from 19.4 +/- 4.8 to 15.5 +/- 6.5 (P = 0.003). Statistical Parametric Mapping 8 and FineSRT analysis showed more severe and widespread regional cerebral blood flow reduction, mainly in the frontal and mesial temporal regions in AD patients with WML compared with those without WML. CONCLUSION: Baseline WML could predict a rapid progression of cognitive and brain functional impairment during longitudinal follow up in AD. Geriatr Gerontol Int 2016; 16: 836-842.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnostic imaging/ physiopathology/psychology;Cerebrovascular Circulation/ physiology;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Tomography, Emission-Computed, Single-Photon;White Matter/ blood supply/ diagnostic imaging;Alzheimer's disease;brain perfusion single-photon emission computed tomography;regional cerebral blood flow;white matter lesions","Hanaoka, T.;Kimura, N.;Aso, Y.;Takemaru, M.;Kimura, Y.;Ishibashi, M.;Matsubara, E.",2016,Jul,,0,4022
4022,Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer's disease,"AIM: The aim of the present study was to evaluate the relationship between baseline white matter lesions (WML) and changes in regional cerebral blood flow during longitudinal follow up of patients with Alzheimer's disease (AD). METHODS: A total of 38 patients with AD were included in the study (16 men, 22 women; mean age 77.8 years). All patients were evaluated using the Mini-Mental State Examination and brain perfusion single-photon emission computed tomography at baseline with an approximately 2-year follow up. The patients were divided into two subgroups according to the presence of WML on magnetic resonance imaging. Single-photon emission computed tomography data were analyzed using a voxel-by-voxel group analysis with Statistical Parametric Mapping 8 and region of interest analysis using FineSRT. Changes in Mini-Mental State Examination scores and regional cerebral blood flow were analyzed using the Wilcoxon signed-rank test. RESULTS: Mean Mini-Mental State Examination scores in AD patients with WML significantly decreased from 19.4 +/- 4.8 to 15.5 +/- 6.5 (P = 0.003). Statistical Parametric Mapping 8 and FineSRT analysis showed more severe and widespread regional cerebral blood flow reduction, mainly in the frontal and mesial temporal regions in AD patients with WML compared with those without WML. CONCLUSION: Baseline WML could predict a rapid progression of cognitive and brain functional impairment during longitudinal follow up in AD. Geriatr Gerontol Int 2015; : -.",,"Hanaoka, T.;Kimura, N.;Aso, Y.;Takemaru, M.;Kimura, Y.;Ishibashi, M.;Matsubara, E.",2015,Aug 5,10.1111/ggi.12563,0,
4023,Financial literacy is associated with white matter integrity in old age,"Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age.",,"Han, S. D.;Boyle, P. A.;Arfanakis, K.;Fleischman, D.;Yu, L.;James, B. D.;Bennett, D. A.",2016,Apr 15,10.1016/j.neuroimage.2016.02.030,0,
4024,"Clinical manifestation, imageological and pathological characteristics of Wernicke encephalopathy","Background: The clinical manifestations of Wernicke encephalopathy(WE) are atypical and short of effective auxiliary examination means. The effects of magnetic resonance imaging (MRI) in the diagnosis of WE have been reported successively. But its imageological detection needs to be further investigated. Objective: To analyze the characteristics of clinical manifestations, skull MRI examination and pathological results in patients with WE. Design: Retrospective analysis. Setting: The General Hospital of Chinese PLA. Participants: Ten patients of WE admitted to the Department of Neurology, General Hospital of Chinese PLA were recruited. Among them, five patients were diagnosed pathologically after death. Their pathological changes accorded with the pathological characteristics of WE. The other 5 patients were diagnosed clinically before death. Their pathological changes accorded with clinical and imageological manifestations and had definite reaction to the treatment of thiamine. Ten patients, 7 males and 3 females, were aged (47±13) years ranging from 33 to 73 years. Their disease courses averaged 6 weeks ranging from 3 to 10 weeks. They all were non-alcoholics. Four patients developed WE after acute pancreatitis, two patients after the recurrence of gastric cancer, two patients after cholecystectomy, one patient after hepatitis medicamentosa, one patient after Alzheimer disease. Informed consents were obtained from all the patients and their relatives. Methods: After admission, clinical manifestations of patients were observed and recorded. Five patients underwent skull MRI examination and their detected results were recorded. Five dead patients underwent autopsy and brain pathological examinations. Neuropathological examination involved cerebrum, cerebellum and brain stem. Main outcome measures: Clinical manifestations, MRI examination results, pathological analysis results and prognosis of all the patients. Results: Ten patients with WE were involved in the final analysis. 1 Nine patients presented various degrees of mental and conscious disturbance. Six patients initially presented vertigo, nausea, and vomiting. Five patients showed opthalmoplegia. Three patients presented hypotension (BP < 120/60 mm Hg, 1 mm Hg= 0.133 kPa). Two patients showed ataxia. One patient showed severe polyneuropathy. Both lower extremities were more severe. EMG showed axonal degeneration. 2 Five patients accepted skull MRI examination. Three patients showed typical high signals in periaqueductal regions and circumference of third and fourth ventriculus in T(2) -weighted and flair-weighted images, two of them showed high signals in fornixes in T(2) -weighted and flair-weighted images, and one of them showed high signals in optic chiasma, both mammillary bodies, and subcortical white matter. No abnormality was found in the other two patients. Two patients who accepted the supplements of thiamine showed obviously improvements in the second MRI examination. 3 Macroscopically, the border between gray and white matters was clear in the coronal section of cerebrum. Congestions, edema and multiple petechial hemorrhages were found in periaqueductal regions, circumference of third and fourth ventriculus, and both mammillary bodies. Microscopically, various degrees of necrosis of parenchymal structures, loss of nerve cells and ischemic changes were found. Myelinated fibers were more affected than neurons. There were focal capillary proliferation and multiple petechial hemorrhages. Prominent astrocytic proliferations were found in gelatinous fiber staining. And demyelinations were found in myelin staining. These pathological findings were all in accord with the diagnostic criteria of WE. 4 In the diagnosis before death, 4 of 5 patients who were supplemented with thiamine had obvious improvement 2 weeks later and 1 of them abandoned therapy due to progressive aggravation of jaundice caused by recurrence of stomach cancer. The other 5 patients who were not diagnosed definitely before death and not supplemented with thiamine died. Final diagnosis w s performed in autopsy examination. Conclusion: The clinical manifestations of this group of WE patients are atypical. MRI and pathological examination results are corresponding, and both have the characteristic manifestations of WE.",,"Han, S. C.;Pu, C. Q.;Gui, Q. P.;Huang, X. S.;Lang, S. Y.;Wu, W. P.;Wang, P. F.",2006,November,,0,
4025,Plasma level of sICAM-1 is associated with the extent of white matter lesion among asymptomatic elderly subjects,"OBJECTIVE: Inflammatory endothelial activation mediated by intercellular adhesion molecule-1 (ICAM-1) plays a role in the pathogenesis of large- and small-vessel disease. We explored the association between soluble ICAM-1 (sICAM-1) and white matter lesion (WML) as a manifestation of cerebral small-vessel disease. METHODS: One hundred and seventy-five elderly individuals aged >or= 60 without neurological deficits were studied. Subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH) were rated separately. Lesions in each category were then divided into three groups (grade 0-I, grade II, grade III) according to the Fazekas scale. RESULTS: Plasma sICAM-1 levels were positively associated with grades of WML (for SDWMH: 297.4+/-135.6ng/mL in grade 0-I, 391.3+/-145.5ng/mL in grade II, and 450.2+/-232.9ng/mL in grade III, p<0.001; for PVH: 282.5+/-116.5ng/mL in grade 0-I, 402.3+/-160.4ng/mL in grade II, and 428.1+/-227.7ng/mL in grade III, p<0.001). Multivariate analysis showed higher sICAM-1 levels, age and hypertension were the independent risk factors associated with the presence and severity of WML. More than 4-fold increased risk of WML was observed in patients with the highest quartile of sICAM-1 (all WML OR=4.694, 95% CI: 1.805-12.204; moderate WML OR=4.618, 95% CI: 1.543-13.825; severe WML OR=4.893, 95% CI: 1.236-19.368). CONCLUSION: Increased plasma sICAM-1 suggests inflammatory process may be involved in the pathogenesis of WML.","Aged;Brain/*pathology;Dementia, Vascular/*blood/*pathology;Diabetes Mellitus/pathology;Female;Humans;Hyperlipidemias/complications/pathology;Hypertension/complications/pathology;Intercellular Adhesion Molecule-1/*blood;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Smoking/pathology","Han, J. H.;Wong, K. S.;Wang, Y. Y.;Fu, J. H.;Ding, D.;Hong, Z.",2009,Dec,10.1016/j.clineuro.2009.08.018,0,
4026,Intravascular lymphomatosis of the brain: Report of a case using an intraoperative cytologic preparation,"BACKGROUND: Intravascular lymphomatosis (IVL) of the brain is a rare non-Hodgkin's lymphoma characterized by proliferation of tumor cells in the lumina of blood vessels. Although an intraoperative cytologic examination of the brain is routinely done, the cytologic features of IVL are rarely encountered by pathologists. We report a case of IVL diagnosed by an intraoperative cytology preparation. CASE: A 62-year-old woman presented with a seizure and fever. Computed tomography and magnetic resonance imaging of the brain were insufficient to establish a diagnosis but suggested a cerebral infarction, so a stereotactic brain biopsy was performed. On an intraoperative cytologic examination, a few small and medium-sized vessels were filled with tumor cells showing atypical, pleomorphic, large nuclei. Immunohistochemical staining using paraffin-embedded tissue revealed intra-luminal tumor cells expressing leukocyte common antigen and CD20 but not CD3. CONCLUSION: This disease must be considered one of the diagnostic possibilities in any patient with rapidly progressive dementia and cerebral infarction. Increased awareness of this disease and intraoperative early diagnosis are important for its successful management.",,"Han, J. H.;Kim, J. H.;Yim, H.",2004,May/June,,0,
4027,"In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET","Neuropathological studies in Alzheimer's disease (AD) indicate specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long cortico-cortical connections, projecting through the corpus callosum, in an anterior-posterior topology. Based on these findings we hypothesized that regional corpus callosum atrophy may be a potential in vivo marker for neocortical neuronal loss in AD. To evaluate this hypothesis, we developed a method to measure cross-sectional area of the corpus callosum and of five corpus callosum subregions on midsagittal magnetic resonance imaging scans (MRI). In a subsequent series of six experimental studies using MRI, (18)FDG-PET and EEG, we investigated the relation of white matter hyperintensities (WMH) to corpus callosum size and correlated regional pattern of corpus callosum atrophy with regional cortical metabolic decline as well as intracortical coherencies. Mean total corpus callosum area was reduced significantly in AD patients compared to healthy age-matched controls, with the greatest changes in the rostrum and the splenium and relative sparing of the truncus. The regional pattern of corpus callosum atrophy was independent of WMH load and correlated significantly with pattern of regional metabolic decline measured with (18)FDG-PET, the degree of cognitive impairment and regional decline of bilateral intracortical-coherency in EEG in AD patients. We further found that hippocampus atrophy, as a marker of early allocortical degeneration, was more pronounced than total corpus callosum atrophy in mild stages of AD. Regional corpus callosum atrophy in mild disease, however, suggested early neocortical degeneration in AD. In a longitudinal study, AD patients showed significantly greater rates of corpus callosum atrophy than controls. Rates of atrophy correlated with progression of clinical dementia severity in AD. Our results indicate that regional corpus callosum atrophy in AD patients represents the loss of callosal efferent neurons in corresponding regions of the neocortex. As these neurons are a subset of cortico-cortical projecting neurons, region-specific corpus callosum atrophy may serve as a marker of progressive neocortical disconnection in AD. In combination with measurement of hippocampal atrophy, assessment of corpus callosum atrophy over time in individual patients is useful to evaluate effects on brain structure of currently developed drugs, thought to slow or modify AD progression.","Alzheimer Disease/ diagnosis/psychology/therapy;Atrophy;Corpus Callosum/pathology/physiopathology/radiography;Disease Progression;Electroencephalography;Fluorodeoxyglucose F18;Hippocampus/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Neocortex/ pathology/physiopathology/ radionuclide imaging;Nerve Degeneration/ diagnosis;Neurons/pathology;Radiopharmaceuticals;Severity of Illness Index;Tomography, Emission-Computed","Hampel, H.;Teipel, S. J.;Alexander, G. E.;Pogarell, O.;Rapoport, S. I.;Moller, H. J.",2002,May,10.1007/s007020200069,0,
4028,Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: A magnetic resonance imaging analysis,"Background: Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. Objectives: To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. Method: Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on mid-sagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. Results: The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. Conclusions: Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neo-cortical disconnection in Alzheimer disease.",,"Hampel, H.;Teipel, S. J.;Alexander, G. E.;Horwitz, B.;Teichberg, D.;Schapiro, M. B.;Rapoport, S. I.",1998,1998,,0,
4029,"Corpus callosum measurement as an in vivo indicator for neocortical neuronal integrity, but not white matter pathology, in Alzheimer's disease",,Alzheimer Disease/*pathology;Brain/anatomy & histology/*pathology;Corpus Callosum/anatomy & histology/*pathology;Frontal Lobe/pathology;Humans;Magnetic Resonance Imaging;Neocortex/pathology;Neurons/*pathology;Pyramidal Cells/pathology;Reference Values,"Hampel, H.;Teipel, S. J.;Alexander, G. E.;Horwitz, B.;Pietrini, P.;Hippius, H.;Moller, H. J.;Schapiro, M. B.;Rapoport, S. I.",2000,Apr,,0,
4030,Imaging glial cell activation with 11C -R-PK11195 in patients with AIDS,"Glial cell activation occurs in response to brain injury and is present in a wide variety of inflammatory processes including dementia associated with human immunodeficiency virus (HIV). HIV-infected glial cells release cytokines and chemokines that, along with viral neurotoxins, contribute to neuronal damage and apoptosis. The purpose of this study was to determine if glial cell activation in HIV-positive (HIV+) patients could be detected noninvasively, in vivo, using [11C]-R-PK11195 with positron emission tomography (PET). [11C]-R-PK11195 is a selective radioligand for the peripheral benzodiazepine receptor (PBR), and is known to reflect the extent of glial cell activation. A subaim was to determine if nondemented HIV+ patients could be distinguished from those with HIV-associated dementia (HAD) on the basis of [11C]-R-PK11195 binding. Five healthy volunteers and 10 HIV+ patients underwent PET with [11C]-R-PK11195. Time-radioactivity curves (TACs) were generated from dynamic PET images in nine regions of interest (ROIs) drawn on coregistered magnetic resonance imaging (MRI) scans. The average radioactivity was calculated in each ROI and was normalized to the average radioactivity in white matter. Patients with HAD showed significantly higher [11C]-R-PK11195 binding than controls in five out of eight brain regions (P < .05, Mann-Whitney U test). Nondemented HIV+ patients did not show significantly increased binding compared to controls. HIV+ patients overall (demented and nondemented) showed significantly higher radioligand binding than controls in five brain regions (P < 0.05). Patients with HAD did not show significant differences in binding when compared to HIV+ nondemented patients. The findings of this pilot study support a role for glial cell activation in HAD, and that PET with [11C]-R-PK11195 can detect the concomitants of neuronal damage in individuals infected with HIV.",AIDS Dementia Complex/immunology/pathology/ radionuclide imaging;Adult;Antineoplastic Agents;Brain/immunology/pathology/radionuclide imaging;Carbon Radioisotopes;Female;Humans;Isoquinolines;Male;Middle Aged;Neuroglia/immunology/ radionuclide imaging/virology;Pilot Projects;Positron-Emission Tomography/ methods,"Hammoud, D. A.;Endres, C. J.;Chander, A. R.;Guilarte, T. R.;Wong, D. F.;Sacktor, N. C.;McArthur, J. C.;Pomper, M. G.",2005,Aug,10.1080/13550280500187351,0,
4031,Variant of multiple sclerosis with dementia and tumefactive demyelinating brain lesions,"We describe an unusual clinical and diagnostic feature of a patient with multiple sclerosis (MS). A 25-year-old woman was admitted to the Neurology department (December 2009) with one month history of rapid cognitive deterioration. She had poor cognition, dysphasia, reduction in visual acuity and temporal pallor of the optic discs. She had prolonged latencies of P100 component of visual evoked potentials (VEPs). Magnetic resonance imaging (MRI)-brain showed multifocal large (>/= 3 cm) white-matter hypointense lesions in T1W and hyperintense in T2W and fluid-attenuated inversion recovery images and patchy enhancement. A diagnosis of tumefactive MS was given. She received two consecutive 5-d courses of 1 g daily intravenous methylprednisolone for 2 mo and oral prednisolone in dose of 80 mg twice/daily in between. At the 3(rd) month, Mini Mental State Examination and VEPs returned to normal but not the MRI. Patient continued oral steroids after hospital discharge (March 2010) for 9 mo with significant MRI improvement after which tapering of steroids started for a year. The patient refused immunomodulation therapy due to her low socioeconomic status. Neither clinical relapse nor new MRI lesions were observed throughout the next 4 years. In spite of the aggressive course of tumefactive MS variant, good prognosis may be seen in some patients.",,"Hamed, S. A.",2015,Jun 16,10.12998/wjcc.v3.i6.525,0,
4032,Abnormal nocturnal blood pressure fall in senile-onset depression with subcortical silent cerebral infarction,"Recent studies have shown that the complication rate of silent cerebral infarction (SCI) in patients with geriatric depression increases with the age at the onset of depression. This study investigated the cardiovascular factors involved in the development of SCI in geriatric depression. Thirty-six patients with geriatric depression were classified according to the age at onset into 16 who developed depression at the age of <50 years (early-onset group) and 20 who developed depression at the age of ≥50 years (late-onset group). The incidence of SCI assessed by subcortical hyperintensity on MRI images, office blood pressure (BP), nocturnal systolic",,"Hamada, T.;Murata, T.;Omori, M.;Takahashi, T.;Kosaka, H.;Wada, Y.;Yoshida, H.",2003,2003,,0,
4033,A progressive neurodegenerative disorder with cortical spongiform change and white matter damage presenting with pseudobulbar palsy,"An autopsy case of spongiform encephalopathy with severe white matter degeneration, beginning with slowly progressive pseudobulbar palsy was reported. A 58-year-old man with no family history of neurologic disease noticed speech disturbance at age 38, which gradually deteriorated. By the age of 41, he became totally aphonic, but he could write and understand the meaning of writing. At age 42, he showed pseudobulbar palsy. At age 43, he gradually developed parkinsonism and generalized hyper-reflexia. At age 46, he showed dementia, aphonia, rigidity, generalized hyper-reflexia, left grasping, and quadriplegia in flexion. He died of respiratory failure at age 58, in the state of akinetic mutism, 20 years after the onset of the symptoms. Neuropathologically, the brain showed marked diffuse atrophy. Microscopic examination revealed spongiform encephalopathy with severe neuronal loss and profound white matter degeneration throughout the cerebrum. This case was difficult to categorize in any known neurodegenerative disease, both clinically and neuropathologically, suggesting a new entity of neurodegenerative disease.",adult;akinetic mutism;article;autopsy;brain atrophy;brain cortex;brain degeneration;brain spongiosis;case report;clinical feature;dementia;disease course;dysphonia;facial nerve paralysis;histopathology;human;hyperreflexia;male;nuclear magnetic resonance imaging;parkinsonism;priority journal;quadriplegia;respiratory failure;rigidity;speech disorder;white matter,"Hamada, K.;Fukazawa, T.;Honma, S.;Takei, A.;Yanagihara, T.;Yoshida, K.;Hamada, T.;Shimoyama, M.;Moriwaka, F.;Tashiro, K.",1997,,,0,
4034,An autopsied case of panencephalopathic-type Creutzfeldt-Jakob disease with mutation in the prion protein gene at codon 232 and type 1 prion protein,"In this study, we describe the clinicopathologic findings in a 68-year-old man with panencephalopathic-type CJD with a substitution from methionine to arginine at codon 232 (M232R) in the prion protein (PrP) gene and type 1 PrP. Initial symptoms of the patient were a rapidly progressive memory disturbance and disorientation. The patient showed myoclonus and periodic sharp-wave complexes on electroencephalogram in the early stages of disease. Diffusion-weighted MRI along with the presence of both neuron-specific enolase and 14-3-3 protein in the CSF showed similarities to classic-type sporadic CJD. The patient reached the akinetic mutism state 2 months following the onset of symptoms and died after 13 months. Neuropathologic examination revealed panencephalopathic-type CJD pathology including widespread neuron loss with severe hypertrophic astrocytosis and status spongiosus in the cerebral gray matter, particularly in the neocortex. Cerebral white matter and the cerebellum also showed severe involvement. Immunohistochemical staining for PrP showed diffuse gray matter staining, indicating synaptic-type PrP deposition without plaque-type. Two different clinical phenotypes of M232R CJD were recognized despite the presence of the same PrP genotype, and the present case is speculated to correspond to the rapid-type. © 2009 Japanese Society of Neuropathology.",arginine;methionine;neuron specific enolase;prion protein;protein 14 3 3;aged;akinetic mutism;amino acid substitution;article;astrocytosis;ataxia;autopsy;Babinski reflex;basal ganglion;bradykinesia;brain atrophy;brain ventricle dilatation;case report;cerebellum;cerebral blindness;cerebrospinal fluid analysis;codon;consciousness disorder;Creutzfeldt Jakob disease;death;dementia;diffusion weighted imaging;disease course;disorientation;dysphagia;electroencephalogram;frontal cortex;gene mutation;genotype;gray matter;human;human tissue;immunohistochemistry;male;memory disorder;mental deterioration;myoclonus;neocortex;nerve cell;occipital cortex;pathological crying;phenotype;pneumonia;priority journal;respiratory failure;temporal cortex;white matter,"Hama, T.;Iwasaki, Y.;Niwa, H.;Yoshida, M.;Hashizume, Y.;Kitamoto, T.;Murakami, N.;Sobue, G.",2009,,,0,
4035,Topography of cortical thinning associated with white matter hyperintensities in Parkinson's disease,"BACKGROUND: Although white matter hyperintensities (WMHs) are associated with cognitive impairments in Parkinson's disease (PD), the relationships between WMHs and cortical atrophy in regard to cognitive impairments are unknown. Here, we investigated the topography of cortical thinning related to deep (DWMHs) and periventricular WMHs (PWMHs) and their differential impacts on cognitive performance in PD. METHODS: We enrolled 87 patients with non-demented PD and evaluated WMH scores using a semi-quantitative visual rating system. The patients were divided into low-, moderate-, and high-grade groups based on WMH severity for total WMHs (TWMHs), DWMHs, and PWMHs, and cortical thickness was measured using a surface-based method according to the WMHs severity. Additionally, the correlations between WMH-associated cortical thinning and neuropsychological performance were analyzed. RESULTS: The detailed neuropsychological test demonstrated that PD patients with high-grade WMHs showed poorer performance on frontal lobe-based cognitive tasks compared with those with low-grade DWMHs. The areas of cortical thinning were more extensive in patients with DWMHs, involving the entire frontal areas and restricted temporoparietal areas, whereas in patients with PWMHs, cortical thinning was localized in the small frontal areas. A multiple regression analysis of the relationships between WMH-associated cortical thickness and cognition revealed that DWMH-associated frontal thickness had an independent effect on frontal lobe-based cognition, while frontal thickness related to PWMHs did not have a significant correlation with cognitive tasks. CONCLUSIONS: These data suggest that in patients with PD, DWMHs are closely coupled with decreased cortical thickness in the frontal areas and may lead to declines in executive function.","Aged;Executive Function/*physiology;Female;Frontal Lobe/*pathology/physiopathology;Humans;Leukomalacia, Periventricular/*pathology;Magnetic Resonance Imaging;Male;Middle Aged;Parkinson Disease/*pathology/physiopathology;White Matter/*pathology;Cortical thinning;Parkinson's disease;White matter hyperintensities","Ham, J. H.;Yun, H. J.;Sunwoo, M. K.;Hong, J. Y.;Lee, J. M.;Sohn, Y. H.;Lee, P. H.",2015,Apr,10.1016/j.parkreldis.2015.01.015,0,
4036,Cerebral microbleeds in patients with Parkinson's disease,"Cerebral microbleeds (CMBs) are known to be associated with cognitive impairments in the elderly and in patients with various diseases; however, the nature of this association has not yet been evaluated in Parkinson's disease (PD). In the present study, we analyzed the incidence of CMBs in PD according to cognitive status, and the impact of CMBs on cognitive performance was also evaluated. The CMBs in PD with dementia (n = 36), mild cognitive impairment (MCI, n = 46), or cognitively normal (n = 41) were analyzed using conventional T2*-weighted gradient-recalled echo images. Additionally, the relationship between the presence of CMBs and cognitive performance on individual tests of cognitive subdomains was analyzed using a detailed neuropsychological test. CMBs occurred more frequently in PD patients with dementia (36.1 %) compared to those with MCI (15.2 %), those who are cognitively normal (14.6 %), and normal controls (12.2 %, p = 0.025). However, the significant association of CMBs with PD dementia disappeared after adjusting white matter hyperintensities (WMHs) as a covariate. The frequencies of deep, lobar, and infratentorial CMBs did not differ among the four groups. After adjusting for age, sex, years of education, and WMHs, PD patients with CMBs had poorer performance in attention domain compared with those without CMBs (34.9 vs 42.6, p = 0.018). The present data demonstrate that even though CMBs were inseparably associated with the presence of WMHs, CMBs occur more commonly in PD patients with dementia than in those without dementia. Additionally, the burden of CMBs may contribute to further cognitive impairment in PD.","Aged;Aged, 80 and over;Brain/pathology;Cerebral Hemorrhage/diagnosis/ etiology;Chi-Square Distribution;Cognition Disorders/ etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Parkinson Disease/ complications;Severity of Illness Index","Ham, J. H.;Yi, H.;Sunwoo, M. K.;Hong, J. Y.;Sohn, Y. H.;Lee, P. H.",2014,Aug,10.1007/s00415-014-7403-y,0,
4037,Effect of olfactory impairment and white matter hyperintensities on cognition in Parkinson's disease,"INTRODUCTION: Although white matter hyperintensities (WMH) and olfactory dysfunction are independently associated with the cognitive impairments in Parkinson's disease (PD), the effects of simultaneous presence of these abnormalities remain unknown. Thus, we investigated the different effects of deep WMH and periventricular WMH on olfactory and cognitive performance and evaluated the additive effects of the concurrent presence of WMH and olfactory dysfunction on cognitive performance in PD. METHODS: We enrolled 171 patients with non-demented PD whose WMH scores were assessed using a semi-quantitative visual rating system. The olfactory and cognitive performance was assessed using the Cross-Cultural Smell Identification (CCSI) test and the Seoul Neuropsychological Screening Battery. Additionally, the additive effects of concurrent WMH and olfactory dysfunction on cognitive performance were investigated using binary logistic regression. RESULTS: The deep WMH score exhibited a significant negative correlation with the CCSI score (p = 0.026) but the total WMH and periventricular WMH did not. A multiple regression analysis revealed that the total WMH (beta = -0.109, p = 0.011) and deep WMH (beta = -0.153, p = 0.020) severities had significant negative correlations with semantic fluency. A logistic regression analysis revealed that the simultaneous presence of severe olfactory dysfunction and deep WMH was associated with a greater risk for the semantic fluency impairments (odds ratio = 15.909, p = 0.0005) compared to patients with mild deep WMH or high CCSI scores. CONCLUSIONS: These data indicate that deep WMH was closely coupled with olfactory impairments and cognitive decline in PD. Moreover, the concurrent presence of severe deep WMH and olfactory impairments has a greater influence on semantic fluency.","Aged;Analysis of Variance;Cognition Disorders/ diagnostic imaging/ etiology;Executive Function;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Olfaction Disorders/diagnostic imaging/ etiology;Parkinson Disease/ complications;ROC Curve;Regression Analysis;Retrospective Studies;Severity of Illness Index;White Matter/ diagnostic imaging/pathology;Cognition;Olfaction;Parkinson's disease;White matter hyperintensities","Ham, J. H.;Lee, J. J.;Sunwoo, M. K.;Hong, J. Y.;Sohn, Y. H.;Lee, P. H.",2016,Mar,,0,
4038,Caffeine in the elderly and MCI,"BACKGROUND: Recent epidemiologic data suggests a positive effect of caffeine in neurodegeneration, notably mild cognitive impairment (MCI) and Alzheimer Dementia. Using functional magnetic resonance imaging, we assessed working memory performance, functional connectivity and baseline perfusion in healthy elderly controls and MCI participants. MATERIALS AND METHODS: Two related prospective, placebo-controlled crossover design studies included 24 healthy elderly individuals (mean age 68.8+/-4.0 years) and 17 MCI (mean age 70.7+/-4.6 years) performing a 2-back working memory task in fMRI. Analyses include complimentary assessment of task-related activations (general linear model, GLM), functional connectivity (tensorial independent component analysis, TICA), and baseline perfusion (arterial spin labeling, ASL) RESULTS: Despite a reduction in whole-brain global perfusion (25.5%, p > 0.001 in HC and 29.9%, p > 0.001 in MCI), caffeine enhanced task-related GLM activation in a distributed network most pronounced in the bilateral striatum and to a lesser degree in the right middle and inferior frontal gyrus, bilateral insula, left superior and inferior parietal lobule as well as in the cerebellum bilaterally. Functional connectivity was significantly enhanced (+8.2%) in caffeine versus placebo in a task-relevant network including the pre-frontal cortex, the supplementary motor area, the ventral premotor cortex and the parietal cortex as well as the occipital cortex (visual stimuli) and basal ganglia in HC. The inverse comparison of placebo versus caffeine had no significant difference. In MCI, caffeine resulted in an increased activation in parietal regions yet decreased activation in frontal regions as compared to HC. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. CONCLUSIONS: The present findings suggest that acute caffeine intake enhances working memory-related brain activation as well as functional connectivity of BOLD fMRI in elderly individuals and more pronounced in MCI. The high caffeine-related activation in the striatum can be attributed to the high local concentration of adenosine receptors. The current results on caffeine will also be discussed with respect to recent investigations illustrating a beneficial effect of chocolate on early stages of dementia.",aged;human;functional magnetic resonance imaging;working memory;perfusion;brain;corpus striatum;spin labeling;independent component analysis;Alzheimer disease;statistical model;density;dementia;crossover procedure;visual stimulation;occipital cortex;parietal cortex;mild cognitive impairment;premotor cortex;supplementary motor area;frontal cortex;cerebellum;inferior parietal lobule;insula;basal ganglion;gray matter;inferior frontal gyrus;white matter;cacao;nerve degeneration;caffeine;placebo;adenosine receptor,"Haller, S.;Rodriguez, C.;Moser, D.;Toma, S.;Hofmeister, J.;Sinanaj, I.;Ville, D.;Giannakopoulos, P.;Lovblad, K. O.",2014,,,0,
4039,Diffusion tensor imaging (DTI) based individual prediction of cognitive decline in mild cognitive impairment using a support vector machine analysis,"The aim of this study was to predict further cognitive decline in mild cognitive impairment (MCI) using an individual level support vector machine (SVM) classification analysis of white matter derived from diffusion tensor imaging (DTI). Thirty-five healthy controls (HC) and 67 MCI subjects had DTI at baseline. MCI subjects were neuropsychologically followed for after one year and categorized into 40 stable (sMCI; 9 single domain amnestic, 7 single domain frontal, 24 multiple domain) and 27 progressive (pMCI; 7 single domain amnestic, 4 single domain frontal, 16 multiple domain). Fractional anisotropy (FA), longitudinal (LD), radial (RD) and mean (MD) diffusivity were assessed using Tract-Based Spatial Statistics (TBSS). Statistical analyses included both group comparisons and individual classification using SVM using 10 fold cross validation. FA was significantly higher in HC compared to MCI in a distributed network including the ventral part of the corpus callosum, right temporal and frontal pathways. There were no significant group-level differences between sMCI versus pMCI or between MCI subtypes after correction for multiple comparisons. SVM analysis allowed for an individual classification with accuracies up to 91.4% (HC versus MCI) and 98.4% (sMCI versus pMCI). When considering the MCI subgroups separately, the minimum SVM classification accuracy for stable versus progressive cognitive decline was 97.5% in the multiple domain MCI group. SVM analysis of DTI data provided highly accurate individual prediction of cognitive decline in MCI regardless of MCI subtype, indicating that this method may become an easily applicable tool for early individual detection of MCI subjects evolving to dementia. © 2011 The authors and IOS Press. All rights reserved.",,"Haller, S.;Nguyen, D.;Rodriguez, C.;Emch, J.;Gold, G.;Bartsch, A.;Lovblad, K. O.;Giannakopoulos, P.",2011,2011,,0,
4040,Individual prediction of cognitive decline in mild cognitive impairment using support vector machine-based analysis of diffusion tensor imaging data,"Although cross-sectional diffusion tensor imaging (DTI) studies revealed significant white matter changes in mild cognitive impairment (MCI), the utility of this technique in predicting further cognitive decline is debated. Thirty-five healthy controls (HC) and 67 MCI subjects with DTI baseline data were neuropsychologically assessed at one year. Among them, there were 40 stable (sMCI; 9 single domain amnestic, 7 single domain frontal, 24 multiple domain) and 27 were progressive (pMCI; 7 single domain amnestic, 4 single domain frontal, 16 multiple domain). Fractional anisotropy (FA) and longitudinal, radial, and mean diffusivity were measured using Tract-Based Spatial Statistics. Statistics included group comparisons and individual classification of MCI cases using support vector machines (SVM). FA was significantly higher in HC compared to MCI in a distributed network including the ventral part of the corpus callosum, right temporal and frontal pathways. There were no significant group-level differences between sMCI versus pMCI or between MCI subtypes after correction for multiple comparisons. However, SVM analysis allowed for an individual classification with accuracies up to 91.4% (HC versus MCI) and 98.4% (sMCI versus pMCI). When considering the MCI subgroups separately, the minimum SVM classification accuracy for stable versus progressive cognitive decline was 97.5% in the multiple domain MCI group. SVM analysis of DTI data provided highly accurate individual classification of stable versus progressive MCI regardless of MCI subtype, indicating that this method may become an easily applicable tool for early individual detection of MCI subjects evolving to dementia.","Aged;Cognition Disorders/ diagnosis/ metabolism/pathology;Diffusion Tensor Imaging/instrumentation/ methods;Female;Follow-Up Studies;Humans;Image Interpretation, Computer-Assisted/instrumentation/ methods;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests","Haller, S.;Nguyen, D.;Rodriguez, C.;Emch, J.;Gold, G.;Bartsch, A.;Lovblad, K. O.;Giannakopoulos, P.",2010,,10.3233/jad-2010-100840,0,
4041,Acute caffeine administration effect on brain activation patterns in mild cognitive impairment,"Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.","Brain [drug effects] [pathology] [physiopathology];Brain Mapping;Caffeine [pharmacology];Central Nervous System Stimulants [pharmacology];Cerebrovascular Circulation [drug effects] [physiology];Cross-Over Studies;Diffusion Tensor Imaging;Gray Matter [drug effects] [pathology] [physiopathology];Magnetic Resonance Imaging;Memory, Short-Term [drug effects] [physiology];Mild Cognitive Impairment [drug therapy] [pathology] [physiopathology];Neural Pathways [drug effects] [pathology] [physiopathology];Neuropsychological Tests;Reaction Time [drug effects];Signal Processing, Computer-Assisted;White Matter [drug effects] [pathology] [physiopathology];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword]","Haller, S.;Montandon, M. L.;Rodriguez, C.;Moser, D.;Toma, S.;Hofmeister, J.;Sinanaj, I.;Lovblad, K. O.;Giannakopoulos, P.",2014,,,0,
4042,Two-step anomalous diffusion tensor imaging,"We extend the formalism of anomalous diffusion imaging to include directional anisotropy of fitted parameters. The resulting technique is termed anomalous diffusion tensor imaging (aDTI), and allows the directional properties of the distributed diffusion coefficient (α) and the anomalous diffusion exponent, (γ) to be analysed using the same analytical techniques as regular diffusion tensor imaging (DTI). Together, these parameters quantify the rate of diffusion (α) and the complexity of the diffusion environment (γ). We generated tensor images for the anomalous exponent tensor (Γ) and distributed diffusivity tensor (A) from in vivo human brain data and present images of eigenvalues, eigenvectors, Trace/3 (Tr), fractional anisotropy (FA) and tensor shape measures. In white matter, A is found to have a median Tr=0.56×10(-3)mm(2)s(-1), FA=0.58 and Γ Tr=0.69",,"Hall, M. G.;Barrick, T. R.",2012,February,,0,
4043,Subclinical atherosclerosis is related to lower neuronal viability in middle-aged adults: A 1H MRS study,"Background: Increased carotid artery intima-media thickness (IMT) is a noninvasive marker of systemic arterial disease, associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. In the elderly, clinically elevated IMT is related to diminished attention-executive function. In this context, previous work involving paper-and-pencil measures of cognition has demonstrated that a threshold of pathology (i.e., IMT ≥ 0.9 mm) is needed before IMT consistently relates to poor neuropsychological test performance. Given the critical role of arterial health in the development of cognitive dysfunction, the goal of this study was to investigate early markers of brain vulnerability by examining subclinical levels of IMT in relation to a sensitive marker of neuronal integrity, cerebral N-acetyl-aspartate/creatine (NAA/Cr) ratio, in midlife. Methods: A total of 40 participants aged 50 ± 6 years, underwent neuropsychological assessment, proton magnetic resonance spectroscopy (1H MRS) examination of occipitoparietal grey matter and B-mode ultrasound of the common carotid artery. IMT was defined as the distance between the luminal-endothelial interface and the junction between the media and the adventitia. The relation between IMT and cerebral metabolite ratios was modeled using a single multivariate multiple regression analysis adjusted for age and current systolic blood pressure. Results: Increased IMT was associated with significantly lower NAA/Cr ratios (IMT beta = -0.62, p = 0.001), independent of age and systolic blood pressure (F(3,36) = 4.928, p = 0.006). Conclusions: Our study extends previous findings by demonstrating a significant relationship between IMT and NAA concentration, suggesting compromised neuronal viability even at IMT levels below thresholds for clinical end-organ damage. © 2010 Elsevier B.V. All rights reserved.",creatine;n acetylaspartic acid;adult;arterial wall thickness;article;atherosclerosis;brain metabolism;clinical article;common carotid artery;controlled study;female;human;male;mental deterioration;neuropsychological test;priority journal;proton nuclear magnetic resonance;systolic blood pressure,"Haley, A. P.;Tarumi, T.;Gonzales, M. M.;Sugawara, J.;Tanaka, H.",2010,,,0,
4044,Subjective cognitive complaints relate to white matter hyperintensities and future cognitive decline in patients with cardiovascular disease,"OBJECTIVE: Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship among self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD. PARTICIPANTS AND METHODS: Forty-seven patients with CVD (aged 55-85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale [CDS]), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small subsample (N = 17). RESULTS: Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F[3, 43] = 4.45, p = 0.008, CDS partial r = -0.30, p = 0.048), independent of age, education, baseline DRS, and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = 0.53, df = 15, p = 0.028). CONCLUSIONS: Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. However, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored.","Aged;Aged, 80 and over;Aging/ physiology;Brain/ pathology;Cardiovascular Diseases/complications/physiopathology/ultrasonography;Cognition Disorders/diagnosis/epidemiology/ etiology/pathology;Female;Forecasting;Geriatric Assessment;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Male;Mental Status Schedule;Middle Aged;Psychiatric Status Rating Scales;Rhode Island;Risk Factors;Surveys and Questionnaires","Haley, A. P.;Hoth, K. F.;Gunstad, J.;Paul, R. H.;Jefferson, A. L.;Tate, D. F.;Ono, M.;Jerskey, B. A.;Poppas, A.;Sweet, L. H.;Cohen, R. A.",2009,Nov,10.1097/JGP.0b013e3181b208ef,0,
4045,The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation,"The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan–Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6 %. At 3 years, 90.6 % of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6 % CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0–4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.",,"Haji, S.;Planchard, R.;Zubair, A.;Graff-Radford, J.;Rydberg, C.;Brown, R. D.;Flemming, K. D.",2016,1,,0,
4046,Carotid artery wall stiffness is increased in patients with small vessel disease: A case-control study,"INTRODUCTION: Cerebral ischemic small-vessel disease (SVD), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (MRI), is a progressive disease associated with an increased risk of stroke, dementia and death. Increased arterial stiffness has been associated with ischemic stroke and cerebral SVD independently of common vascular risk factors. OBJECTIVE: The aim of the study was to analyze arterial stiffness in our patients with symptomatic SVD. METHODS: In a cross-sectional study design we included 30 patients with clinical and MRI evidence of cerebral SVD and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. Patients were evaluated at the Ultrasound Laboratory at the Neurology Clinic, Clinical Center of Serbia in Belgrade, during a three-month period (from September 1st to December 1st 2012). Baseline demographic and vascular risk factors were recorded. All patients underwent standard carotid ultrasound scans with measuring of intima-media thickness (IMT) and analysis of atheromatous plaques. Internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (BSI) value. RESULTS: There were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p > 0.05). Patients in SVD group had significantly higher mean IMT (p = 0.0093) and mean BSI (p < 0.0001) than subjects in the control group. No significant correlation was detected between IMT and BSI in SVD group (r = 0.168; p = 0.376). Brain lesions severity correlated with BSI (r = 0.733; p < 0.0001). CONCLUSION: Arterial stiffness is increased in symptomatic patients with SVD, independently of vascular risk factors and IMT.",Aged;*Carotid Arteries/pathology/ultrasonography;Carotid Intima-Media Thickness;Carotid Stenosis/pathology/ultrasonography;Case-Control Studies;*Cerebral Small Vessel Diseases/epidemiology/pathology/ultrasonography;Cross-Sectional Studies;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Vascular Stiffness/*physiology,"Hajdarevic, D. S.;Pavlovic, A. M.;Smajlovic, D.;Podgorac, A.;Jovanovic, Z.;Medjedovic, T. S.;Sternic, N. C.",2016,Jan-Feb,,0,
4047,"Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia","BACKGROUND AND PURPOSE: We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). METHODS: Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). RESULTS: Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P=0.007). CONCLUSIONS: Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.","Aged;Aged, 80 and over;Blood-Brain Barrier/ pathology/physiopathology;Dementia/ pathology/physiopathology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Prospective Studies;White Matter/ pathology/physiopathology;dementia;fibrinogen;leukoaraiosis;neuropathology;vascular cognitive impairment;white matter","Hainsworth, A. H.;Minett, T.;Andoh, J.;Forster, G.;Bhide, I.;Barrick, T. R.;Elderfield, K.;Jeevahan, J.;Markus, H. S.;Bridges, L. R.",2017,Oct,,0,
4048,Dissociable effects of Alzheimer disease and white matter hyperintensities on brain metabolism,"IMPORTANCE: Cerebrovascular disease and Alzheimer disease (AD) frequently co-occur and seem to act through different pathways in producing dementia. OBJECTIVE: To examine cerebrovascular disease and AD markers in relation to brain glucose metabolism in patients with mild cognitive impairment. DESIGN AND SETTING: Cohort study among the Alzheimer Disease Neuroimaging Initiative clinical sites in the United States and Canada. PARTICIPANTS: Two hundred three patients having amnestic mild cognitive impairment (74 of whom converted to AD) with serial imaging during a 3-year follow-up period. MAIN OUTCOMES AND MEASURES: Quantified white matter hyperintensities (WMHs) represented cerebrovascular disease, and cerebrospinal fluid beta-amyloid represented AD pathology. Brain glucose metabolism in temporoparietal and frontal brain regions was measured using positron emission tomography with fluorodeoxyglucose F18. RESULTS: In converters, greater WMHs were associated with decreased frontal metabolism (-0.048; 95% CI, -0.067 to -0.029) but not temporoparietal metabolism (0.010; 95% CI, -0.010 to 0.030). Greater cerebrospinal fluid beta-amyloid (per 10-pg/mL increase) was associated with increased temporoparietal metabolism (0.005; 95% CI, 0.000-0.010) but not frontal metabolism (0.002; 95% CI, -0.004 to 0.007) in the same patients. In nonconverters, similar relationships were observed except for a positive association of greater WMHs with increased temporoparietal metabolism (0.051; 95% CI, 0.027-0.076). CONCLUSIONS AND RELEVANCE: The dissociation of WMHs and cerebrospinal fluid beta-amyloid in relation to regional glucose metabolism suggests that these pathologic conditions operate through different and independent pathways in AD that reflect dysfunction in different brain systems. The positive association of greater WMHs with temporoparietal metabolism suggests that these pathologic processes do not co-occur in nonconverters.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/ metabolism/ pathology;Amyloid beta-Peptides/cerebrospinal fluid/metabolism;Biomarkers/cerebrospinal fluid/metabolism;Brain Injuries/cerebrospinal fluid/ metabolism/ pathology;Cerebrovascular Disorders/cerebrospinal fluid/metabolism/pathology;Cohort Studies;Female;Follow-Up Studies;Humans;Leukoencephalopathies/cerebrospinal fluid/ metabolism/ pathology;Male;Middle Aged;Mild Cognitive Impairment/cerebrospinal fluid/metabolism/pathology","Haight, T. J.;Landau, S. M.;Carmichael, O.;Schwarz, C.;DeCarli, C.;Jagust, W. J.",2013,Aug,10.1001/jamaneurol.2013.1878,0,
4049,The neuroanatomy of general intelligence: sex matters,"We examined the relationship between structural brain variation and general intelligence using voxel-based morphometric analysis of MRI data in men and women with equivalent IQ scores. Compared to men, women show more white matter and fewer gray matter areas related to intelligence. In men IQ/gray matter correlations are strongest in frontal and parietal lobes (BA 8, 9, 39, 40), whereas the strongest correlations in women are in the frontal lobe (BA10) along with Broca's area. Men and women apparently achieve similar IQ results with different brain regions, suggesting that there is no singular underlying neuroanatomical structure to general intelligence and that different types of brain designs may manifest equivalent intellectual performance.","Adolescent;Adult;Aged;Aged, 80 and over;Alzheimer Disease/pathology;Brain/*pathology;Dominance, Cerebral/physiology;Down Syndrome/pathology;Female;Frontal Lobe/pathology;Humans;*Image Processing, Computer-Assisted;*Imaging, Three-Dimensional;Intelligence/*physiology;*Magnetic Resonance Imaging;Male;Mathematical Computing;Middle Aged;Reference Values;*Sex Characteristics;Statistics as Topic","Haier, R. J.;Jung, R. E.;Yeo, R. A.;Head, K.;Alkire, M. T.",2005,Mar,10.1016/j.neuroimage.2004.11.019,0,
4050,Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics,"The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer's disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naive subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p(corrected)<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p(corrected)<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.","Aged;Aged, 80 and over;Alzheimer Disease/*physiopathology;Anisotropy;*Apathy;Brain/*physiopathology;Brain Mapping/methods;Corpus Callosum/metabolism/*physiopathology;Diffusion Tensor Imaging/methods;Female;Humans;Magnetic Resonance Imaging/methods;Male;Models, Statistical;Nerve Fibers, Myelinated/*pathology;Reproducibility of Results","Hahn, C.;Lim, H. K.;Won, W. Y.;Ahn, K. J.;Jung, W. S.;Lee, C. U.",2013,,10.1371/journal.pone.0053493,0,
4051,Plasma parathyroid hormone is associated with vascular dementia and cerebral hyperintensities in two community-based cohorts,"Context: In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.Objective: We sought to investigate relations between PTH clinical dementia and cerebral microvascular disease.Setting and Design: The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.Participants and Main Outcome Measure: In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.Results: During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P< .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1SDPTHincrease, 0.31 higher category ofWMHI; P=.016). All modelswereadjusted for vascular risk factors and mineral metabolism.Conclusions: In two community-based samples, PTH predicted clinically diagnosed vascular dementia as well as neuroimaging indices of cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.",,"Hagström, E.;Kilander, L.;Nylander, R.;Larsson, E. M.;Michaëlsson, K.;Melhus, H.;Ahlström, H.;Johansson, L.;Lind, L.;Ärnlöv, J.",2014,1,,0,
4052,A clinical study on the usefulness of CT and MRI imaging in evaluating differential diagnosis and the degree of dementia in vascular dementia,"For the evaluation of differential diagnosis and estimation of the functional prognosis for vascular dementia (VD), the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) in detecting cerebro-vascular lesions was compared. Then the correlations between the degrees of mental function (Hasegawa's dementia rating scale: HDRS, activity of daily living: ADL, troublesome behaviors: TB) and the CT findings of vascular dementia were examined retrospectively. A hundred and seventeen dementia patients (male: 79 cases, female: 38 cases; mean-age 69.5 +/- 10.9 years old), diagnosed using DSM-III criteria, were scored according to Hachinski's ischemic score (I.S.) by clinical course and symptoms. Both MRI and CT were carried out on 56 dementia cases (male: 21 cases, female: 35 cases; mean-age 78.0 +/- 7.4 years old) at the chronic stage of the cerebro-vascular accidents to compare the detectiveness of vascular lesions. In 90 vascular dementia patients on whom only CT was carried out, the imagings were classified according to number, size, and localization. The correlation between these parameters and the degree of dementia were examined retrospectively. MRI was more useful and sensitive than CT for differentiating VD from DAT (dementia of Alzheimer type), since MRI was superior to CT in detecting small infarcts or lacunaes on the perforating area or white matter. Cases with positive findings on CT or MRI but clinically diagnosed as DAT by I.S. showed poorer ADL.(ABSTRACT TRUNCATED AT 250 WORDS)","Aged;Dementia, Vascular/ diagnosis/pathology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Hagiwara, M.",1990,Jun,,0,
4053,Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL,"A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.","Adult;Age of Onset;Brain/ pathology/ultrastructure;Child;Dementia, Multi-Infarct/ pathology;Dementia, Vascular/ diagnosis/ genetics/physiopathology;Diagnosis, Differential;Female;Germany;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Male;Microscopy, Electron;Middle Aged;Pedigree;Polymerase Chain Reaction;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface/genetics;Tomography, X-Ray Computed","Hagel, C.;Groden, C.;Niemeyer, R.;Stavrou, D.;Colmant, H. J.",2004,Sep,10.1007/s00401-004-0887-2,0,
4054,Increased frequency of white matter lesions in patients with osteonecrosis (WMLeOn) of the femoral head,"White matter lesions (WML) are commonly seen in cerebral MR imaging in normal and demented elderly people or young people suffering from migraine. We present data showing that WML are detected in an unexpectedly high frequency (56.9%) in patients with non-traumatic osteonecrosis of the femoral head compared to age and sex-matched controls. We designated the coexistence of WML and osteonecrosis as white matter lesions in osteonecrosis (WMLeON). We examined the possible association of WMLeON with hyperlipidaemia and other risk factors for WML or osteonecrosis of the femoral head. The frequency of history of corticosteroid treatment was statistically lower in patients with WMLeON (58.6%) compared to those without it (90.1%) (P=0.03). We found no association of WMLeON with diabetes, stroke, hyperlipidaemia, migraine, smoking, alcohol consumption, hypertension, atrial fibrillation, or systemic lupus erythematosus. Although, the clinical significance of WMLeON is still unknown, this finding supports, at least, the hypothesis that non-traumatic osteonecrosis is indeed a multisystem disorder rather than a disease of human skeleton. © 2004 Elsevier Ireland Ltd. All rights reserved.",,"Hadjigeorgiou, G. M.;Karantanas, A. H.;Zibis, A.;Dardiotis, E.;Aggelakis, K.;Papadimitriou, A.;Malizos, K.",2004,June,,0,
4055,Cross-sectional study of unexplained white matter lesions in hiv positive individuals undergoing brain magnetic resonance imaging,"White matter (WM) abnormalities are frequently seen on brain MRI of HIV positive (HIV+) patients. We aimed to determine the prevalence of unexplained WM abnormalities and their associations with HIV disease and cardiovascular risk factors. We conducted a retrospective, cross-sectional study of brain MRI of HIV+ patients conducted between 2004 and 2009 at our center. Clinical and laboratory data were compiled, and images were independently reviewed for WM lesions. Images were obtained from 254 patients: 70% male, 53% white, 40% black, mean age 42 years, median current CD4 count 240 cells/mm(3), and 41% not taking antiretroviral therapy (ART). Hyperintense WM lesions were present in 161 patients (63.4%): 89 scans (35.0%) showed diffuse WM signal abnormality (DWMSA), 61 (24.0%) were consistent with small vessel disease (SVD, graded by Fazekas' scale), and 37 (14.6%) showed large asymmetrical focal WM lesions. SVD changes were associated with age and cardiovascular risk factors, and while cerebral SVD may be related to HIV infection, the MRI findings were not associated with HIV-related factors. The only risk factor for DWMSA was black race, and no correlation with cardiovascular risk factors, CD4 count, or clinical presentation was identified. DWMSA are therefore of uncertain neurological significance in HIV+ patients and could represent more than one clinicopathological entity. © 2014, Mary Ann Liebert, Inc. 2014.",,"Haddow, L. J.;Dudau, C.;Chandrashekar, H.;Cartledge, J. D.;Hyare, H.;Miller, R. F.;Jäger, H. R.",2014,2014,,0,
4056,Recurrent status epilepticus as the primary neurological manifestation of CADASIL: A case report,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) often presents with a history of migraine with aura and eventual manifestations of dementia with unrelenting, repeated cerebral vascular insults. Only 6-10% of patients with CADASIL have been reported to develop seizures, and status epilepticus (SE) is exceedingly rare. Here, we describe a patient who presented with recurrent SE, with eventual biopsy diagnosis of CADASIL. An 80-year-old woman presented to our hospital three times in two years with decreased level of consciousness and subtle intermittent right-sided upper extremity and facial twitching. There was no known significant family history and no past medical history for seizures, stroke, migraine headache, or overt dementia. Electroencephalography revealed recurrent focal seizures with left hemispheric onset and evolution, fulfilling the criteria for focal SE each time. All three admissions required sedation with midazolam to control seizure activity, in addition to high doses of multiple antiepileptic drugs. Brain MRI repeatedly showed extensive abnormalities in the periventricular and deep white matter, subcortical white matter, and bilateral basal ganglia. Skin biopsy was obtained on the third admission, and electron microscopy showed numerous deposits of granular osmiophilic material, which are pathognomonic for CADASIL. Detailed investigations failed to reveal any other etiology for the patient's condition. This case illustrates the potential for nonconvulsive SE to be the sole manifestation of CADASIL. With the appropriate brain MRI findings, CADASIL should be added to the list of rare causes of SE.","Cadasil;CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and;leukoencephalopathy;CSF, cerebrospinal fluid;Eeg;Mri;PEG, percutaneous endoscopic gastrostomy;SE, status epilepticus;Seizures;Status epilepticus","Haddad, N.;Ikard, C.;Hiatt, K.;Shanmugam, V.;Schmidley, J.",2015,,10.1016/j.ebcr.2015.02.004,0,
4057,Leuko-araiosis,"Problems in the literature in the appraisal of brain deep white-matter changes are considered. The identification of the changes with Binswanger's disease alone is rejected, and evidence is reviewed that demonstrates that they are associated with cognitive impairment and, to some extent, with vascular disease. Possible causes of white-matter changes and their relationships to Alzheimer's disease are examined, and it is argued that a neutral term, exact enough to define white-matter changes, sufficient as a description or label, and demanding enough to require precise clinical and imaging descriptions is needed. We suggest herein the term ""leuko-araiosis"" on the basis of Greek etymology and Hippocratic usage.","Brain/ pathology;Brain Diseases/ diagnosis/pathology;Dementia/ diagnosis/pathology;Humans;Magnetic Resonance Spectroscopy;Myelin Sheath/ pathology;Terminology as Topic;Tomography, X-Ray Computed","Hachinski, V. C.;Potter, P.;Merskey, H.",1987,Jan,,0,
4058,Neurobehavioral changes and hypertension: The 'athymhormic syndrome',"In 3 hypertensive patients, aged 57 to 66, profound behavioral and personality changes occurred rather abruptly, characterized by total loss of spontaneous activity and initiative, apathetic behavior, passivity, lack of drive and motivation, loss of interest for any of previous occupations and hobbies, and total flatness of affect. Neurological examination was normal or only showed mild extrapyramidal signs. Neuropsychological evaluation was only remarkable for mild intellectual impairment suggestive of frontal lobe dysfunction. None of the 3 patients fulfilled criteria for dementia or severe depression. This neurobehavioral syndrome has been coined 'athymhormic syndrome' (Habib and Poncet, 1988) a term emphasizing the specific defect in drive ('horme') and affect ('thumos'). Electrical and clinical heart examination was unremarkable. Blood pressure was always found within normal limits during hospitalization, including 24-hour monitoring in one case. However, all patients were known as hypertensive in the past, with repeated bouts of high blood pressure (up to 270 mmHg systolic in one case). X-ray CT-scan was usually normal or showed non-specific white matter changes (so-called 'leukoaraiosis'). In all 3 cases, a brain MRI scan showed multiple small infarcts mainly involving deep subcortical structures (caudate nuclei and/or adjacent periventricular white matter) of both hemispheres, consistent with the definition of lacunes. This clinico-radiological syndrome appears as a specific entity whose pathophysiology may be discussed by reference to anatomical patterns of vasculature of the periventricular deep cerebral structures: the specific location of lacunes in the 3 patients indicates ischemic damage affecting the most distal territory of the long perforating arteries of the brain, suggesting reduced blood flow rather than arteriolar occlusions or dilatation of perivascular spaces, as usually invoked for the production of lacunes. It is proposed that bouts of HBP, beside their specific effect on the wall of small arteries, may have resulted in disruption of autoregulation processes, mainly expressing itself as ischemia in the most distal arteriolar territories. For the neurologist, recognizing this syndrome should prompt to search for bouts of HBP and to perform a brain MRI, even though CT-scan is normal. For cardiologists or internal medicine physicians, this syndrome is also worth knowing to evaluate the potential risk of certain forms of hypertension and for accurate appreciation of the neurological handicap. Finally, it may be the case that such cerebral lesions have a 'therapeutic' effect on the hypertensive disease as well as on the development of the lacunar lesions, as a result of changes in affective reactivity to the environment.",adult;aged;apathy;article;brain infarction;case report;human;hypertension;priority journal,"Habib, M.;Royere, M. L.;Habib, G.;Bonnefoi, B.;Milandre, L.;Poncet, M.;Luccioni, R.;Khalil, R.",1991,,,0,
4059,White matter hyperintensities and imaging patterns of brain ageing in the general population,"White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n= 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P< 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P< 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P= 0.001), diabetes mellitus (P= 0.023), smoking (P= 0.002) and education level (P= 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia.",,"Habes, M.;Erus, G.;Toledo, J. B.;Zhang, T.;Bryan, N.;Launer, L. J.;Rosseel, Y.;Janowitz, D.;Doshi, J.;Van der Auwera, S.;von Sarnowski, B.;Hegenscheid, K.;Hosten, N.;Homuth, G.;Volzke, H.;Schminke, U.;Hoffmann, W.;Grabe, H. J.;Davatzikos, C.",2016,Apr,10.1093/brain/aww008,0,
4060,Optimization of brain PET imaging for a multicentre trial: the French CATI experience,"BACKGROUND: CATI is a French initiative launched in 2010 to handle the neuroimaging of a large cohort of subjects recruited for an Alzheimer's research program called MEMENTO. This paper presents our test protocol and results obtained for the 22 PET centres (overall 13 different scanners) involved in the MEMENTO cohort. We determined acquisition parameters using phantom experiments prior to patient studies, with the aim of optimizing PET quantitative values to the highest possible per site, while reducing, if possible, variability across centres. METHODS: Jaszczak's and 3D-Hoffman's phantom measurements were used to assess image spatial resolution (ISR), recovery coefficients (RC) in hot and cold spheres, and signal-to-noise ratio (SNR). For each centre, the optimal reconstruction parameters were chosen as those maximizing ISR and RC without a noticeable decrease in SNR. Point-spread-function (PSF) modelling reconstructions were discarded. The three figures of merit extracted from the images reconstructed with optimized parameters and routine schemes were compared, as were volumes of interest ratios extracted from Hoffman acquisitions. The net effect of the 3D-OSEM reconstruction parameter optimization was investigated on a subset of 18 scanners without PSF modelling reconstruction. RESULTS: Compared to the routine parameters of the 22 PET centres, average RC in the two smallest hot and cold spheres and average ISR remained stable or were improved with the optimized reconstruction, at the expense of slight SNR degradation, while the dispersion of values was reduced. For the subset of scanners without PSF modelling, the mean RC of the smallest hot sphere obtained with the optimized reconstruction was significantly higher than with routine reconstruction. The putamen and caudate-to-white matter ratios measured on 3D-Hoffman acquisitions of all centres were also significantly improved by the optimization, while the variance was reduced. CONCLUSIONS: This study provides guidelines for optimizing quantitative results for multicentric PET neuroimaging trials.",,"Habert, M. O.;Marie, S.;Bertin, H.;Reynal, M.;Martini, J. B.;Diallo, M.;Kas, A.;Trebossen, R.",2016,Dec,10.1186/s40658-016-0141-8,0,
4061,General fluid-type intelligence is related to indices of white matter structure in middle-aged and old adults,"General fluid-type intelligence (gF) reflects abstract reasoning and problem solving abilities, and is an important predictor for lifetime trajectories of cognition, and physical and mental health. Structural and functional neuroimaging studies have demonstrated the role of parieto-frontal gray matter, but the white matter (WM) underpinnings of gF and the contribution of individual gF components to gF-WM relationship still need to be explored. Theaim of this study was to characterize, in a sample of 100 healthy middle-aged and old subjects (mean. = 63.8. years), the relationship between gF and indices of WM structure obtained from diffusion tensor magnetic resonance imaging (DT-MRI) (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD)). gF was estimated by principal component analysis including measures of episodic memory, reasoning, and processing speed. Tract-based spatial statistics and permutation-based inference statistics were used to test the association between gF and WM indices, while controlling for the effect of age and sex. We hypothesized a positive relationship between gF and WM structure. Based on previous studies, we further hypothesized that this relationship was heavily influenced by the processing speed component of gF. Wefound a robust relationship between gF and DT-MRI measures of FA, RD and MD in all major WM tracts. Higher gF score was related to higher degree of WM integrity, in middle-aged as well as old individuals. Thus, the distributed relationship between gF and indices of WM microstructure is consistent with the notion that gF reflects efficient signaling between cortical areas. Furthermore, analysis of relationships between WM measures and gF components revealed an association with information processing speed and reasoning ability, but not with episodic memory. Thus, although all subcomponents loaded high on gF factor, the speed-related components were most strongly associated with",,"Haász, J.;Westlye, E. T.;Fjær, S.;Espeseth, T.;Lundervold, A.;Lundervold, A. J.",2013,December,,0,
4062,Hereditary cerebral haemorrhage with amyloidosis - Dutch type. Magnetic resonance imaging findings in 7 cases,"The clinical history and magnetic resonance imaging (MRI) findings are presented of 7 patients with hereditary cerebral haemorrhage with amyloidosis - Dutch type (HCHWA-D). The diagnosis was based on clinical and genealogical data, was confirmed in 3 patients at autopsy and in 2 others by biopsy. Focal neurological signs, and at least some degree of global cognitive deterioration, were observed in all patients, with unequivocal dementia in 4. MRI showed haemorrhages and areas of gliosis and, to a variable extent, hyperintensity of the white matter in T2-weighted images. Neuropathological examination revealed a large recent haemorrhage together with residual lesions from previous haemorrhages or infarcts in all patients examined. The white matter lesions, present on MRI, turned out to be areas of 'incomplete infarction' with demyelination. It is concluded that (hereditary) amyloid angiopathy can lead to strokes, but also to subcortical ischaemic encephalopathy. Amyloid angiopathy should therefore be considered in the differential diagnosis of white matter lesions, found on CT or MRI, especially when patients present with a cerebral haemorrhage. The relationship between HCHWA-D and Alzheimer's disease, another disease with cerebral amyloid deposition and diffuse white matter involvement, is discussed.",,"Haan, J.;Roos, R. A. C.;Algra, P. R.;Lanser, J. B. K.;Bots, G. T. A. M.;Vegter-Van Der Vlis, M.",1990,1990,,0,
4063,Hereditary cerebral haemorrhage with amyloidosis--Dutch type. Magnetic resonance imaging findings in 7 cases,"The clinical history and magnetic resonance imaging (MRI) findings are presented of 7 patients with hereditary cerebral haemorrhage with amyloidosis--Dutch type (HCHWA-D). The diagnosis was based on clinical and genealogical data, was confirmed in 3 patients at autopsy and in 2 others by biopsy. Focal neurological signs, and at least some degree of global cognitive deterioration, were observed in all patients, with unequivocal dementia in 4. MRI showed haemorrhages and areas of gliosis and, to a variable extent, hyperintensity of the white matter in T2-weighted images. Neuropathological examination revealed a large recent haemorrhage together with residual lesions from previous haemorrhages or infarcts in all patients examined. The white matter lesions, present on MRI, turned out to be areas of 'incomplete infarction' with demyelination. It is concluded that (hereditary) amyloid angiopathy can lead to strokes, but also to subcortical ischaemic encephalopathy. Amyloid angiopathy should therefore be considered in the differential diagnosis of white matter lesions, found on CT or MRI, especially when patients present with a cerebral haemorrhage. The relationship between HCHWA-D and Alzheimer's disease, another disease with cerebral amyloid deposition and diffuse white matter involvement, is discussed.","Adult;Amyloidosis/*diagnosis;Brain/pathology;Cerebral Hemorrhage/*diagnosis;Female;Genetic Diseases, Inborn/diagnosis;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Netherlands;Neuropsychological Tests;Pedigree","Haan, J.;Roos, R. A.;Algra, P. R.;Lanser, J. B.;Bots, G. T.;Vegter-Van der Vlis, M.",1990,Oct,,0,
4064,Establishing a baseline phase behavior in magnetic resonance imaging to determine normal vs. abnormal iron content in the brain,"Purpose: To establish a baseline of phase differences between tissues in a number of regions of the human brain as a means of detecting iron abnormalities using magnetic resonance imaging (MRI). Materials and Methods: A fully flow-compensated, three-dimensional (3D), high-resolution, gradient-echo (GRE) susceptibility-weighted imaging (SWI) sequence was used to collect magnitude and phase data at 1.5T. The phase images were high-pass-filtered and processed region by region with hand-drawn areas. The regions evaluated included the motor cortex (MC), putamen (PUT), globus pallidus (GP), caudate nucleus (CN), substantia nigra (SN), and red nucleus (RN). A total of 75 subjects, ranging in age from 55 to 89 years, were analyzed. Results: The phase was found to have a Gaussian-like distribution with a standard deviation (SD) of 0.046 radians on a pixel-by-pixel basis. Most regions of interest (ROIs) contained at least 100 pixels, giving a standard error of the mean (SEM) of 0.0046 radians or less. In the MC, phase differences were found to be roughly 0.273 radians between CSF and gray matter (GM), and 0.083 radians between CSF and white matter (WM). The difference between CSF and the GP was 0.201 radians, and between CSF and the",,"Haacke, E. M.;Ayaz, M.;Khan, A.;Manova, E. S.;Krishnamurthy, B.;Gollapalli, L.;Ciulla, C.;Kim, I.;Petersen, F.;Kirsch, W.",2007,August,,0,
4065,A voxel-based morphometric study of cortical gray matter volume changes in Alzheimer's disease with white matter hyperintensities,"White matter hyperintensity (WMH) is commonly detected in patients with Alzheimer's disease (AD), but its role in cortical impairment is unclear. This study investigated the effects of WMH on gray matter (GM) volume in patients with AD. We consecutively enrolled 84 patients with AD and 35 normal controls, who underwent brain MRI and were then classified according to WMH grade, based on a combination of deep white matter hyperintensity (DWMH) and periventricular white matter hyperintensity (PVWMH). The volume changes in GM were observed using voxel-based morphometry. It was found that global GM volume decreased with increasing WMH. Regional atrophies were in the dorsolateral frontal lobes, orbitofrontal gyri and insula (false discovery rate [FDR], p<0.01). After controlling for PVWMH, DWMH affected cortical atrophy in the frontal lobe, insula and precuneus (FDR, p<0.05), but PVWMH did not. Thus, WMH in AD is associated with GM volume reduction, especially in the frontal lobe, and DWMH is independently related to cortical atrophy.","Aged;Alzheimer Disease/*pathology;Analysis of Variance;Atrophy;Brain Mapping;Cerebral Cortex/*pathology;Female;Humans;Image Processing, Computer-Assisted;Male","Ha, S. Y.;Youn, Y. C.;Kim, S.;Hsiung, G. Y.;Ahn, S. W.;Shin, H. W.;Park, K. Y.;Park, T. H.;Kim, S. S.;Kee, B. S.;Kwon, O. S.",2012,Nov,10.1016/j.jocn.2011.11.041,0,
4066,What can DTI tell about early cognitive impairment? – Differentiation between MCI subtypes and healthy controls by diffusion tensor imaging,"Mild cognitive impairment (MCI) gained a lot of interest recently, especially that the conversion rate to Alzheimer Disease (AD) in the amnestic subtype (aMCI) is higher than in the non-amnestic subtype (naMCI). We aimed to determine whether and how diffusion-weighted MRI (DWI) using the diffusion tensor model (DTI) can differentiate MCI subtypes from healthy subjects. High resolution 3D T1W and DWI images of patients (aMCI, n = 18; naMCI, n = 20; according to Petersen criteria) and controls (n = 27) were acquired at 3T and processed using ExploreDTI and SPM. Voxel-wise and region of interest (ROI) analyses of fractional anisotropy (FA) and mean diffusivity (MD) were performed with ANCOVA; MD was higher in aMCI compared to controls or naMCI in several grey and white matter (GM, WM) regions (especially in the temporal pole and the inferior temporal lobes), while FA was lower in WM ROI-s (e.g. left Cingulum). Moreover, significant correlations were identified between verbal fluency, visual and verbal memory performance and DTI metrics. Logistic regression showed that measuring FA of the crus of fornix along GM volumetry improves the discrimination of aMCI from naMCI. Additional information from DWI/DTI aids preclinical detection of AD and may help detecting early non-Alzheimer type dementia, too.",NCT02310620;nuclear magnetic resonance scanner;aged;angular gyrus;article;brain region;clinical article;controlled study;differential diagnosis;diffusion tensor imaging;diffusion weighted imaging;early diagnosis;female;fractional anisotropy;human;inferior frontal gyrus;male;middle temporal gyrus;mild cognitive impairment;neuroimaging;neuropsychological test;parahippocampal gyrus;pars triangularis;priority journal;prognosis;staging;stria terminalis;superior frontal gyrus;superior temporal gyrus;trail making test;verbal memory;visual memory;Achieva,"Gyebnár, G.;Szabó, Á;Sirály, E.;Fodor, Z.;Sákovics, A.;Salacz, P.;Hidasi, Z.;Csibri, É;Rudas, G.;Kozák, L. R.;Csukly, G.",2018,,10.1016/j.pscychresns.2017.10.007,0,
4067,White matter hyperintensities and amyloid are independently associated with entorhinal cortex volume among individuals with mild cognitive impairment,"BACKGROUND: Current hypothetical models of Alzheimer's disease (AD) pathogenesis emphasize the role of beta-amyloid (Abeta), tau deposition, and neurodegenerative changes in the mesial temporal lobe, particularly the entorhinal cortex and hippocampus. However, many individuals with clinical AD who come to autopsy also exhibit cerebrovascular disease. The relationship between AD and vascular pathology is unclear, especially whether they represent additive and independent effects on neuronal injury. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to (1) confirm whether entorhinal cortex and hippocampal volume are associated with memory among individuals with amnestic mild cognitive impairment (MCI) who are at risk for AD; and (2) determine whether regional white matter hyperintensity (WMH) volume, a radiological marker of small-vessel cerebrovascular disease, is associated with entorhinal cortex and hippocampal volume independent of putative AD biomarkers in this group. METHODS: Cognitive test scores, entorhinal cortex volume, hippocampus volume, intracranial volume, and cerebrospinal fluid-derived phosphorylated tau and Abeta1-42 protein levels were measured in 199 subjects with amnestic MCI (mean age = 74.89 +/- 7.47). Lobar WMH volumes were derived from T1-, proton-density-, and T2-weighted magnetic resonance imaging scans. We examined the association between entorhinal cortex volume and cognition. Next, we examined the association of tau and Abeta1-42 with entorhinal cortex volume and between lobar WMH and entorhinal cortex volume. Finally, tau, Abeta1-42, and regional WMH volumes were entered simultaneously to predict entorhinal cortex volume. We repeated the analyses with hippocampal volume instead of entorhinal cortex volume. The analyses were also repeated with the sample restricted to those MCI patients who transitioned to AD on subsequent ADNI follow-up visits (n = 86). RESULTS: Larger entorhinal cortex volume was associated with better memory but not with performance on a task of executive functioning. Lower levels of Abeta1-42 and higher temporal WMH volumes were associated with smaller entorhinal cortex volume. When entered simultaneously, temporal lobe WMH volume was more reliably associated with entorhinal cortex volume than was Abeta1-42. The findings were similar for hippocampus volume and when the sample was restricted to MCI patients who subsequently transitioned to AD. CONCLUSIONS: The findings confirm the role of entorhinal cortex and hippocampus volume in influencing memory decline in amnestic MCI, and emphasize that even in this nominally AD prodromal condition, WMH may be influencing regional neurodegeneration.","Aged;Aged, 80 and over;Amyloid beta-Peptides/ metabolism;Entorhinal Cortex/ metabolism/ pathology;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Mental Recall/physiology;Mild Cognitive Impairment/ pathology;Models, Statistical;Nerve Fibers, Myelinated/metabolism/ pathology;Neuropsychological Tests;Peptide Fragments/ metabolism;tau Proteins/metabolism","Guzman, V. A.;Carmichael, O. T.;Schwarz, C.;Tosto, G.;Zimmerman, M. E.;Brickman, A. M.",2013,Oct,10.1016/j.jalz.2012.11.009,0,
4068,Small arterial granular degeneration in familial Binswanger's syndrome,"A 55-year-old mildly hypertensive woman died after having developed a subcortical dementia during the past 9 years, with focal neurological signs. She presented at the age of 46 years with short episodes of dizziness and diplopia, suggesting that transient ischemic attacks involved the posterior fossa structures. Over the next 8 years, she developed difficulty in walking, urinary incontinence and seizures. On examination in 1989, she was severely demented. There was tetraparesis, bilateral arm and leg spasticity with hyperreflexia and bilateral Babinski signs. She showed epilepsia partialis continua involving the eyes, left hemiface and limbs. CT showed hypodensity of the white matter and lacunes in the basal ganglia and centrum semiovale, moderate hydrocephalus with cerebellar and cortical atrophy. Clinical and radiological features were similar to those of Binswanger's disease. Similar cases had occurred in the family affecting the patient's grandfather, father and two brothers, suggesting an autosomal dominant hereditary disease. Postmortem examination disclosed a Binswanger type of leukoencephalopathy caused by a peculiar microangiopathy characterized by a slightly basophilic small arterial granular degeneration of the medial sheath associated with the presence of ballooned smooth muscle cells with clear cytoplasm. Electron microscopic study revealed degenerative changes in the parietal vessels with notable increase of basal-membrane-type material and electron-dense granular deposits. These lesions could correspond to a specific familial pathology of the small arteries of the brain. They are identical to those reported in some patients with autosomal dominant inheritance. For other patients with similar clinical features and the same familial pattern, reported as 'hereditary multi-infarct dementia' and 'cronic familial vascular encephalopathy' there are no sufficient objective pathological facts to consider that they have the same disease. The absence of amyloid pathology in our case differentiates it from the hereditary central nervous system amyloid angiopathies. Finally, patients with non-familial Binswanger's syndrome, but without hypertension, could exceptionally have the same vascular granular degeneration. Presumably, this vasculopathy of uncertain pathogenesis could be related to a metabolic disorder of the basement membrane of smooth muscle cells.",adult;artery disease;article;Babinski reflex;basal ganglion;Binswanger encephalopathy;borderline hypertension;brain atherosclerosis;brain atrophy;case report;dementia;diplopia;epileptic state;female;human;hydrocephalus;hyperreflexia;leukoaraiosis;posterior fossa;priority journal;quadriplegia;seizure;spasticity;transient ischemic attack;urine incontinence;vertigo;white matter,"Gutierrez-Molina, M.;Caminero Rodriguez, A.;Martinez Garcia, C.;Arpa Gutierrez, J.;Morales Bastos, C.;Amer, G.",1994,,,0,
4069,Dementia syndrome and hippocampal sclerosis. A case report with a family history of dementia familial,"Dementia is an acquired clinical syndrome, of an organic nature, characterized by impairment of memory and other mental functions, with or without psycho-behavioral symptoms, where he has been excluded from any altered state of consciousness that affects the functioning of the individual's social activity. Has been described the association of dementia clinically similar to frontotemporal dementia (FTD) and hippocampal sclerosis (HS), where there is severe neuronal loss and gliosis of CA1 of the hippocampus and subiculum. Importantly, the HS has been identified in other cases of primary degenerative diseases, including Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal dementia, vascular dementia, and ischemia in patients with bilateral medial temporal lobe, multiple brain infarcts and leukoencephalopathy. We present a 38-year-old woman with severe cognitive impairment and family history of dementia, on the brain image only found the presence of hippocampal sclerosis. We don't find in the literature descriptions the association of family with dementia and sclerosis hippocampal. We present a brief review of the association of dementia syndrome and hippocampal sclerosis. © Copyright Indice Mexicano de Revistas Biomédicas Latinoamericanas 1998 - 2011.",,"Gutiérrez-Manjarrez, F. A.;Ruiz-Sandoval, J. L.",2011,January-February,,0,
4070,Anatomically guided voxel-based partial volume effect correction in brain PET: impact of MRI segmentation,"Partial volume effect is still considered one of the main limitations in brain PET imaging given the limited spatial resolution of current generation PET scanners. The accuracy of anatomically guided partial volume effect correction (PVC) algorithms in brain PET is largely dependent on the performance of MRI segmentation algorithms partitioning the brain into its main classes, namely gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). A comparative evaluation of four brain MRI segmentation algorithms bundled in the successive releases of Statistical Parametric Mapping (SPM) package (SPM99, SPM2, SPM5, SPM8) using clinical neurological examinations was performed. Subsequently, their impact on PVC in (18)F-FDG brain PET imaging was assessed. The principle of the different variants of the image segmentation algorithm is to spatially normalize the subject's MR images to a corresponding template. PET images were corrected for partial volume effect using GM volume segmented from coregistered MR images. The PVC approach aims to compensate for signal dilution in non-active tissues such as CSF, which becomes an important issue in the case of tissue atrophy to prevent a misinterpretation of decrease of metabolism owing to PVE. The study population consisted of 19 patients suffering from neurodegenerative dementia. Image segmentation performed using SPM5 was used as reference. The comparison showed that previous releases of SPM (SPM99 and SPM2) result in larger gray matter regions (~20%) and smaller white matter regions (between -17% and -6%), thus introducing non-negligible bias in PVC PET activity estimates (between 30% and 90%). In contrary, the more recent release (SPM8) results in similar results (<1%). It was concluded that the choice of the segmentation algorithm for MRI-guided PVC in PET plays a crucial role for the accurate estimation of PET activity concentration. The segmentation algorithm embedded within the latest release of SPM satisfies the requirement of robust and accurate segmentation for MRI-guided PVC in brain PET imaging.","Aged;Aged, 80 and over;Algorithms;Artifacts;Brain/ pathology/ radionuclide imaging;Dementia/ diagnosis;Female;Fluorodeoxyglucose F18;Humans;Image Enhancement/methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Positron-Emission Tomography/ methods;Radiopharmaceuticals;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Gutierrez, D.;Montandon, M. L.;Assal, F.;Allaoua, M.;Ratib, O.;Lovblad, K. O.;Zaidi, H.",2012,Dec,10.1016/j.compmedimag.2012.09.001,0,
4071,Inherited disease of arteries causing brain infarcts and dementia,"CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) is a neurovascular disease caused by mutations of the notch3 gene, manifesting with strokes or stroke-like episodes, psychiatric symptoms, migraine and dementia. The diagnosis can be confirmed by screening exons of this gene. Involvement of the anterior temporal lobe and external capsule on MRI and presence of granular osmiophilic material on skin biopsy may help in diagnosis. We present two Norwegian families with eight members who have symptoms indicating CADASIL. The mutation R182C was demonstrated in exon 4 in seven; one refused gene testing. Two brothers without symptoms also tested positively for this gene mutation.",Notch3 receptor;adult;aged;article;brain infarction;CADASIL;clinical article;dementia;exon;female;gene mutation;human;male;migraine;Norway;nuclear magnetic resonance imaging;skin biopsy;cerebrovascular accident;temporal lobe,"Gustavsen, W. R.;Eiklid, K.",2003,,,0,
4072,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL): A case report with review of literature,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited arterial disease, commonly overlooked or misdiagnosed. We report a case of CADASIL in a 51 years old woman who presented with progressive subcortical dementia, recurrent ischemic events and seizures in the absence of known vascular risk factors of five years' duration. Her mother had a history of similar illness. Magnetic resonance imaging (MRI) of brain revealed subcortical and deep white matter hyperintense lesions within the cerebral white matter on T2-weighted images. DNA mutation of Notch 3 gene confirmed the diagnosis of CADASIL.",,"Gurumukhani, J. K.;Ursekar, M.;Singhal, B. S.",2004,1,,0,
4073,Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study,"OBJECTIVE: We hypothesized that vascular amyloid contributes to chronic brain ischemia, therefore amyloid burden measured by Pittsburgh compound B retention on positron emission tomography (PiB PET) would correlate with the extent of magnetic resonance imaging (MRI) white matter hyperintensities (WMH; or leukoaraiosis) in patients with high vascular amyloid deposition (cerebral amyloid angiopathy [CAA]) but not in patients with high parenchymal amyloid deposition (Alzheimer disease [AD]; mild cognitive impairment [MCI]) or in healthy elderly (HE) subjects. METHODS: Forty-two nondemented CAA patients, 50 HE subjects, and 43 AD/MCI patients had brain MRI and PiB PET. Multivariate linear regression was used to assess the independent association between PiB retention and white matter disease volume, controlling for age, gender, apolipoprotein E genotype, and vascular risk factors within each group. RESULTS: CAA patients were younger than HE and AD subjects (68 +/- 10 vs 73.3 +/- 7 and 74 +/- 7.4, p < 0.01) but had higher amounts of WMH (median = 21 vs 3.2 and 10.8 ml, respectively, p < 0.05 for both comparisons). Global PiB retention and WMH showed strong correlation (rho = 0.52, p < 0.001) in the CAA group but not in HE or AD. These associations did not change in the multivariate models. Lobar microbleed count, another marker of CAA severity, also remained as an independent predictor of WMH volume. INTERPRETATION: Our results indicate that amyloid burden in CAA subjects (with primarily vascular amyloid) but not AD subjects (with primarily parenchymal amyloid) independently correlates with WMH volume. These findings support the idea that vascular amyloid burden directly contributes to chronic cerebral ischemia and highlights the possible utility of amyloid imaging as a marker of CAA severity.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/radionuclide imaging;Aniline Compounds;Apolipoprotein E4/genetics;Cerebral Amyloid Angiopathy/complications/pathology/radionuclide imaging;Cognition Disorders/etiology/pathology/radionuclide imaging;Female;Humans;Leukoaraiosis/complications/pathology/radionuclide imaging;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography;Statistics, Nonparametric;Thiazoles","Gurol, M. E.;Viswanathan, A.;Gidicsin, C.;Hedden, T.;Martinez-Ramirez, S.;Dumas, A.;Vashkevich, A.;Ayres, A. M.;Auriel, E.;van Etten, E.;Becker, A.;Carmasin, J.;Schwab, K.;Rosand, J.;Johnson, K. A.;Greenberg, S. M.",2013,Apr,10.1002/ana.23830,0,
4074,Cerebral amyloid angiopathy in asymptomatic community-dwelling older adults,"Background: Cerebral amyloid angiopathy (CAA), characterized by accumulation of beta-amyloid in cortical vessels, is an established cause of hemorrhagic and ischemic brain damage. Although Boston criteria can accurately diagnose CAA in patients who had lobar intracerebral hemorrhage (ICH), its value in asymptomatic older adults is unknown. Objective: We aimed to compare the amyloid load, structural MRI measures and risk factors between asymptomatic subjects who would qualify for a diagnosis of probable CAA based on lobar microbleeds (LMB) and superficial siderosis (SS) to subjects without these MRI findings. Methods: Healthy older adults (n=181) prospectively enrolled in Harvard Aging Brain study had research MRIs and Pittsburgh Compound B (PiB) PET scans. Probable CAA was diagnosed based on presence of 2 or more LMBs or a combination of LMB/SS. Distribution volume ratio (DVR) of PiB-retention, white matter hyperintensity (WMH) and hippocampal volume (HV) were calculated. Demographics, APOE status, risk factors, and imaging markers were compared between subjects with and without probable CAA diagnosed based on LMB/SS. Results: Participants had mean age 74.5+/-5.8 and 56% were female. Forty-six (25%) subjects had lobar MBs, 11(6%) had deep and 4(2%) cerebellar MBs. The 22 subjects diagnosed with probable CAA had higher occipital DVR (1.35 vs 1.28, p=0.004) and higher WMH (0.51 vs 0.16, p=0.005) when compared to persons without MB. These associations remained significant after adjustment for age and gender. Age, HV, ApoE status and vascular risk factors were similar between probable CAA and no MB/SS subjects (all p>0.2). Conclusions: Probable CAA diagnosis based on presence of lobar MBs and/or SS on MRI of healthy elderly volunteers is associated with other radiologic markers of CAA (posterior amyloid load, WMH) but not with vascular risk factors or markers of Alzheimer's Disease (HV, ApoE 4). Boston criteria and amyloid imaging thus may allow early diagnosis of CAA even in asymptomatic subjects without ICH or dementia.",cerebrovascular accident;vascular amyloidosis;adult;aging;nuclear magnetic resonance imaging;cognitive defect;community;American;nursing;heart;positron emission tomography;human;risk factor;imaging;United States;diagnosis;brain hemorrhage;female;patient;dementia;early diagnosis;brain damage;aged;gender;white matter;volunteer;volume of distribution ratio;brain;siderosis;Alzheimer disease;amyloid;marker;Pittsburgh compound B,"Gurol, M. E.;Schultz, A. P.;Fotiadis, P.;Hedden, T.;Becker, J. A.;Sperling, R. A.;Greenberg, S. M.;Johnson, K. A.",2016,,,0,
4075,"Plasma β-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy","Background: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating β-amyloid peptide in microvascular dysfunction and white matter disease. Methods: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of β-amyloid (Aβ40 and Aβ42) detected by specific enzyme-linked immunosorbent assays. Results: Plasma Aβ40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p ≤ 0.005). Plasma Aβ40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Aβ40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons). Conclusions: Plasma β-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating β-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly. Copyright © 2006 by AAN Enterprises, Inc.",amyloid beta protein;amyloid beta protein[1-40];amyloid beta protein[1-42];apolipoprotein E;biological marker;creatinine;cyanocobalamin;folic acid;homocysteine;age;aged;Alzheimer disease;article;blood vessel injury;brain infarction;brain injury;brain size;cognitive defect;diabetes mellitus;disease severity;enzyme linked immunosorbent assay;female;genotype;human;hypertension;major clinical study;male;nuclear magnetic resonance imaging;priority journal;protein blood level;risk factor;vascular amyloidosis;white matter,"Gurol, M. E.;Irizarry, M. C.;Smith, E. E.;Raju, S.;Diaz-Arrastia, R.;Bottiglieri, T.;Rosand, J.;Growdon, J. H.;Greenberg, S. M.",2006,,,0,
4076,"Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy","BACKGROUND: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease. METHODS: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (Abeta40 and Abeta42) detected by specific enzyme-linked immunosorbent assays. RESULTS: Plasma Abeta40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p < or = 0.005). Plasma Abeta40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Abeta40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons). CONCLUSIONS: Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.","Aged;Aged, 80 and over;Alzheimer Disease/blood/*diagnosis/physiopathology;Amyloid beta-Peptides/*blood;Biomarkers/blood;Brain/blood supply/*pathology/physiopathology;Brain Infarction/blood/diagnosis/physiopathology;Cerebral Amyloid Angiopathy/blood/*diagnosis/physiopathology;Cerebral Arteries/metabolism/pathology/physiopathology;Cerebrovascular Disorders/blood/diagnosis/physiopathology;Cognition Disorders/blood/*diagnosis/physiopathology;Cross-Sectional Studies;Female;Humans;Male;Microcirculation/metabolism/pathology/physiopathology;Middle Aged;Nerve Fibers, Myelinated/metabolism/*pathology;Peptide Fragments/*blood;Predictive Value of Tests;Prognosis","Gurol, M. E.;Irizarry, M. C.;Smith, E. E.;Raju, S.;Diaz-Arrastia, R.;Bottiglieri, T.;Rosand, J.;Growdon, J. H.;Greenberg, S. M.",2006,Jan 10,10.1212/01.wnl.0000191403.95453.6a,0,
4077,Predicting sites of new hemorrhage with amyloid imaging in cerebral amyloid angiopathy,"OBJECTIVE: We aimed to determine whether amyloid imaging can help predict the location and number of future hemorrhages in cerebral amyloid angiopathy (CAA). METHODS: We performed a longitudinal cohort study of 11 patients with CAA without dementia who underwent serial brain MRIs after baseline amyloid imaging with Pittsburgh compound B (PiB). Mean distribution volume ratio (DVR) of PiB was determined at the sites of new micro/macrobleeds identified on follow-up MRI and compared with PiB retention at ""simulated"" hemorrhages, randomly placed in the same subjects using a probability distribution map of CAA-hemorrhage location. Mean PiB retention at the sites of observed new bleeds was also compared to that in shells concentrically surrounding the bleeds. Finally the association between number of incident bleeds and 3 regional amyloid measures were obtained. RESULTS: Nine of 11 subjects had at least one new microbleed on follow-up MRI (median 4, interquartile range [IQR] 1-9) and 2 had 5 new intracerebral hemorrhages. Mean DVR was greater at the sites of incident bleeds (1.34, 95% confidence interval [CI] 1.23-1.46) than simulated lesions (1.14, 95% CI 1.07-1.22, p < 0.0001) in multivariable models. PiB retention decreased with increasing distance from sites of observed bleeds (p < 0.0001). Mean DVR in a superior frontal/parasagittal region of interest correlated independently with number of future hemorrhages after adjustment for relevant covariates (p = 0.003). CONCLUSIONS: Our results provide direct evidence that new CAA-related hemorrhages occur preferentially at sites of increased amyloid deposition and suggest that PiB-PET imaging may be a useful tool in prediction of incident hemorrhages in patients with CAA.","Aged;Aged, 80 and over;Amyloid/ metabolism;Brain/metabolism/ pathology/radionuclide imaging;Brain Mapping;Cerebral Amyloid Angiopathy/metabolism/ pathology/radionuclide imaging;Female;Humans;Image Processing, Computer-Assisted;Intracranial Hemorrhages/metabolism/ pathology/radionuclide imaging;Magnetic Resonance Imaging;Male;Middle Aged;Predictive Value of Tests;Prospective Studies","Gurol, M. E.;Dierksen, G.;Betensky, R.;Gidicsin, C.;Halpin, A.;Becker, A.;Carmasin, J.;Ayres, A.;Schwab, K.;Viswanathan, A.;Salat, D.;Rosand, J.;Johnson, K. A.;Greenberg, S. M.",2012,Jul 24,10.1212/WNL.0b013e31826043a9,0,
4078,Florbetapir PET to diagnose cerebral amyloid angiopathy,"Introduction: Previous studies showed that Pittsburgh Compound B (PiB) labels vascular amyloid characteristic of cerebral amyloid angiopathy (CAA) on PET scans; PiB is not approved for clinical use, however. Hypothesis: We hypothesized that Florbetapir, an FDA-approved PET tracer, can detect amyloid in CAA and help distinguish CAA-related intracerebral hemorrhage (ICH) from hypertensive ICH (HTN-ICH). Methods: We prospectively enrolled non-demented survivors of primary ICH related to probable CAA (per Boston Criteria, n=10) and HTN-ICH (n=9). All patients underwent Florbetapir-PET, multimodal MRI, and additional PiB-PET for the CAA patients. Amyloid burden was assessed quantitatively using parametric maps and also visually, classified as positive or negative. Spatial correlations between Florbetapir and PiB retention were used to test vascular amyloid binding in CAA. We have tested the diagnostic value of Florbetapir by comparing global and occipital mean Florbetapir retention (standard uptake value ratio, SUVR) as well as Florbetapir positive/negative status between CAA and HTN-ICH groups. Results: The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex and white matter hyperintensity volumes (31ml vs 30ml, all p>0.8). Florbetapir uptake and PiB retention strongly correlated in CAA patients both globally within cerebral cortex (r=0.96, p<0.001) and regionally in occipital, frontal, temporal, parietal cortices (all r>0.8, all p<0.01). Mean global cortical Florbetapir uptake was significantly higher in CAA than HTN-ICH (SUVR: 1.41+/-0.16 vs 1.16+/-0.08, p=0.001) as was mean occipital SUVR (1.44+/-0.12 vs 1.17+/-0.08, p<0.001), remaining independent after correcting for global SUVR (p=0.02). Visual rating for Florbetapir positive/negative demonstrated perfect interrater agreement (k=1) between two trained neurologists blinded to all other information and was positive for all 10 CAA patients vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%). Conclusions: Florbetapir, like PiB, appears to label vascular amyloid in patients with CAA-related ICH. Data using the approved Florbetapir binary visual reading method suggest sufficient sensitivity and specificity for diagnostic use in appropriate clinical settings.",cerebrovascular accident;vascular amyloidosis;cognitive defect;nuclear magnetic resonance imaging;brain hemorrhage;American;nursing;heart;positron emission tomography;human;patient;brain cortex;white matter;diagnostic value;parietal cortex;survivor;diagnosis;United States;hypothesis;sensitivity and specificity;reading;neurologist;food and drug administration;amyloid;Pittsburgh compound B;tracer,"Gurol, M. E.;Becker, J. A.;Riley, G. A.;Fotiadis, P.;Schwab, K. M.;Johnson, K. A.;Greenberg, S. M.",2016,,,0,
4079,'Behavioral imaging' - A procedure for analysis and display of neuropsychological test scores: I. Construction of algorithm and initial clinical evaluation,"We present a procedure for quantitation and topographic display of behavioral data related to regional brain function obtained in standard neuropsychological testing. The algorithm applies theoretical probability weightings to actual test scores. The weightings reflect the likelihood that damage in given regions causes deficits on each neuropsychological measure. Initial testing of the algorithm in clinical cases is presented. There was consistency between the 'behavioral images' and the location of the lesion in two patients with unilateral cerebral infarcts. For a pair of twins with Alzheimer's disease the image of the more impaired twin showed greater bilateral involvement. The results encourage further evaluation of the potential of this algorithm for clinical and research use, particularly as a tool for comparing behavioral and neuroimaging data.",,"Gur, R. C.;Trivedi, S. S.;Saykin, A. J.;Gur, R. E.",1988,1988,,0,
4080,Cerebral vasomotor reactivity of patients with acute ischemic stroke: Cortical versus subcortical infarcts: An Israeli-Turkish collaborative study,"Background: Cerebral hemodynamic features of patients with different types of acute ischemic stroke are still obscure. We compared cerebral vasomotor reactivity (VMR) in acute cortical (CI) and subcortical (SI) brain infarcts. Methods: Acute stroke patients (within 72 h of stroke onset) underwent transcranial Doppler and the Diamox test (1 g acetazolamide IV). The percent difference between blood flow velocities in the middle cerebral arteries before and after acetazolamide was defined as VMR%. CI and SI infarcts were confirmed by computerized tomography and/or magnetic resonance imaging. Clinical status and disability were assessed by means of the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) respectively.VMR% values and stroke severity and disability parameters were compared between CI and SI groups using ANOVA and Pearson's correlation (r) coefficients. Results: VMR% values of the ipsilateral side to the brain infarct in the CI group were significantly lower as compared with SI group (12.2 ±15.9% and 25.6 ± 24.4% respectively, P = 0.03). VMR% values in both groups were not correlated with stroke severity and disability (P < 0.2). Conclusions: Our results suggest greater vulnerability of resistance arterioles in the setting of cortical gray matter infarcts. Although gray matter VMR is physiologically higher than white matter VMR, patients with acute CI have impaired cerebral vascular reserve. © 2007 Elsevier B.V. All rights reserved.",,"Gur, A. Y.;Gücüyener, D.;Üzüner, N.;Gilutz, Y.;Özdemir, G.;Korczyn, A. D.;Bornstein, N. M.",2007,15,,0,
4081,"Periventricular white matter changes and dementia. Clinical, neuropsychological, radiological, and pathological correlation","Forty-three patients with computed tomographic scan findings of decreased attenuation in the periventricular white matter (PVWM) region were studied. Clinical evaluation revealed presence of hypertension in 36 patients (84%) and cerebrovascular risk factors in 41 patients (95%). Unilateral or bilateral neurological deficits were present in 40 patients (93%). Neuropsychological evaluation in 27 of them revealed features of subcortical dementia. Magnetic resonance imaging in seven cases demonstrated high-intensity areas in the deep white matter region on T2-weighted imaging. Pathological evaluation in four patients revealed demyelination without inflammatory cells and infarctions in the PVWM region, lacunar infarctions in the basal ganglia and brain stem, and marked arteriosclerosis. The study indicated that most (95% in this series) of the patients with computed tomographic scan findings of decreased attenuation in the PVWM region had cerebrovascular risk factors and various neurological and neuropsychological features of subcortical dementia. Pathologically, these lesions represented areas of infarction and demyelination, along with diffuse arteriosclerosis.",Adult;Aged;Brain/ pathology/radiography;Cerebral Ventricles/ pathology;Cerebral Ventriculography;Dementia/diagnosis/ pathology/psychology;Humans;Male;Middle Aged;Neuropsychological Tests,"Gupta, S. R.;Naheedy, M. H.;Young, J. C.;Ghobrial, M.;Rubino, F. A.;Hindo, W.",1988,Jun,,0,
4082,Voxel-based assessment of gray and white matter volumes in Alzheimer's disease,"Using the study-specific templates and optimized voxel-based morphometry (VBM), this study investigated abnormalities in gray and white matter to provide depiction of the concurrent structural changes in 13 patients with Alzheimer's disease (AD) compared with 14 age- and sex-matched normal controls. Consistent with previous studies, patients with AD exhibited significant gray matter volume reductions mainly in the hippocampus, parahippocampal gyrus, insula, superior/middle temporal gyrus, thalamus, cingulate gyrus, and superior/inferior parietal lobule. In addition, white matter volume reductions were found predominately in the temporal lobe, corpus callosum, and inferior longitudinal fasciculus. Furthermore, a number of additional white matter regions such as precentral gyrus, cingulate fasciculus, superior and inferior frontal gyrus, and sub-gyral in parietal lobe were also affected. The pattern of gray and white matter volume reductions helps us understand the underlying pathologic mechanisms in AD and potentially can be used as an imaging marker for the studies of AD in the future.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Guo, X.;Wang, Z.;Li, K.;Li, Z.;Qi, Z.;Jin, Z.;Yao, L.;Chen, K.",2010,Jan 4,10.1016/j.neulet.2009.10.086,0,
4083,Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis,"Alzheimer's disease (AD) is a neurodegenerative disease concomitant with grey and white matter damages. However, the interrelationship of volumetric changes between grey and white matter remains poorly understood in AD. Using joint independent component analysis, this study identified joint grey and white matter volume reductions based on structural magnetic resonance imaging data to construct the covariant networks in twelve AD patients and fourteen normal controls (NC). We found that three networks showed significant volume reductions in joint grey-white matter sources in AD patients, including (1) frontal/parietal/temporal-superior longitudinal fasciculus/corpus callosum, (2) temporal/parietal/occipital-frontal/occipital, and (3) temporal-precentral/postcentral. The corresponding expression scores distinguished AD patients from NC with 85.7%, 100% and 85.7% sensitivity for joint sources 1, 2 and 3, respectively; 75.0%, 66.7% and 75.0% specificity for joint sources 1, 2 and 3, respectively. Furthermore, the combined source of three significant joint sources best predicted the AD/NC group membership with 92.9% sensitivity and 83.3% specificity. Our findings revealed joint grey and white matter loss in AD patients, and these results can help elucidate the mechanism of grey and white matter reductions in the development of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Brain Mapping/ methods;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Sensitivity and Specificity","Guo, X.;Han, Y.;Chen, K.;Wang, Y.;Yao, L.",2012,Dec 7,10.1016/j.neulet.2012.10.038,0,
4084,Study of diffusion tensor imaging in subcortical ischemic vascular cognitive impairment,"Objective: Using diffusion tensor imaging (DTI) to explore the microstructure changes of white matter in subcortical ischemic vascular cognitive impairment (SIVCI) and its correlation with cognitive function. Methods: Forty-nine patients with subcortical ischemic cerebrovascular diseases were collected. By using Clinical Dementia Rating Scale (CDR), they were classified into 10 cases of vascular dementia (VaD group), 20 cases of vascular cognitive impairment-no dementia (VCIND group) and 19 cases of normal cognitive function (control group). Conventional MRI and DTI were performed in all cases. Based on the DTI data, voxel-based analysis was used to assess the whole brain region. Correlation analysis was applied to illustrate the relationship between DTI parameters and cognitive scale in VaD patients. Results: Compared with the control group, fractional anisotropy (FA) values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes, right temporal lobe and bilateral orbitofrontal lobes (P=0.000, for all), and FA values of patients in VCIND group decreased in right inferior frontal gyrus, right hippocampus and bilateral precuneus (P=0.000, for all). Compared with VCIND group, FA values of patients in VaD group decreased in medial prefrontal cortex, anterior cingulate, corpus callosum, bilateral parietal lobes and right temporal lobe (P=0.000, for all). Compared with the control group, mean diffusivity (MD) values in VaD group increased in medial prefrontal cortex, corpus callosum, bilateral parietal lobes, bilateral temporal lobes and anterior cingulate (P=0.000, for all), while in VCIND group increased in bilateral precuneus and right hippocampus (P=0.000, for all). Compared with VCIND group, MD values in VaD group increased in right medial prefrontal cortex, anterior cingulate cortex, corpus callosum stem, bilateral parietal lobes and bilateral temporal lobes (P=0.000, for all). The correlation analysis showed that the",,"Guo, H. Y.;Sun, F.;Zhang, Z. J.;Zhang, Z. Q.;Qi, R. F.;Ma, S. Y.;Lu, G. M.",2014,Apr.,,0,
4085,Evaluation of common structural brain changes in aging and Alzheimer disease with the use of an MRI-based brain atrophy and lesion index: a comparison between T1WI and T2WI at 1.5T and 3T,"BACKGROUND AND PURPOSE: The Brain Atrophy and Lesion Index combines several common, aging-related structural brain changes and has been validated for high-field MR imaging. In this study, we evaluated measurement properties of the Brain Atrophy and Lesion Index by use of T1WI and T2WI at 1.5T and 3T MR imaging to comprehensively assess the usefulness of the lower field-strength testing. MATERIALS AND METHODS: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative. Images of subjects (n = 127) who had T1WI and T2WI at both 3T and 1.5T on the same day were evaluated, applying the Brain Atrophy and Lesion Index rating. Criterion and construct validity and interrater agreement were tested for each field strength and image type. RESULTS: Regarding reliability, the intraclass correlation coefficients for the Brain Atrophy and Lesion Index score were consistently high (>0.81) across image type and field strength. Regarding construct validity, the Brain Atrophy and Lesion Index score differed among diagnostic groups, being lowest in people without cognitive impairment and highest in those with Alzheimer disease (F > 5.14; P < .007). Brain Atrophy and Lesion Index scores correlated with age (r > 0.37, P < .001) and cognitive performance (r > 0.38, P < .001) and were associated with positive amyloid-beta test (F > 3.96, P < .050). The T1WI and T2WI Brain Atrophy and Lesion Index scores were correlated (r > 0.93, P < .001), with the T2WI scores slightly greater than the T1WI scores (F > 4.25, P < .041). Regarding criterion validation of the 1.5T images, the 1.5T scores were highly correlated with the 3T Brain Atrophy and Lesion Index scores (r > 0.93, P < .001). CONCLUSIONS: The higher field and T2WI more sensitively detect subtle changes in the deep white matter and perivascular spaces in particular. Even so, 1.5T Brain Atrophy and Lesion Index scores are similar to those obtained by use of 3T images. The Brain Atrophy and Lesion Index may have use in quantifying the impact of dementia on brain structures.",Aged;Aging;Alzheimer Disease/ pathology;Atrophy;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Neuroimaging/ methods,"Guo, H.;Song, X.;Vandorpe, R.;Zhang, Y.;Chen, W.;Zhang, N.;Schmidt, M. H.;Rockwood, K.",2014,Mar,10.3174/ajnr.A3709,0,
4086,MRI assessment of whole-brain structural changes in aging,"PURPOSE: One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. MATERIALS AND METHODS: Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7+/-7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7+/-9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9+/-9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. RESULTS: Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r(2)>0.69; P<0.00001). They were associated with age (r(2)>0.29; P<0.00001) and differed by cognitive status (chi(2)>26.48, P<0.00001). T2-FLAIR revealed a greater level of periventricular (chi(2)=29.09) and deep white matter (chi(2)=26.65, P<0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI (P<0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE. CONCLUSION: The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.",MRI pulse sequences;aging;brain atrophy and lesion index (BALI);brain health;structural brain changes,"Guo, H.;Siu, W.;D'Arcy, R. C.;Black, S. E.;Grajauskas, L. A.;Singh, S.;Zhang, Y.;Rockwood, K.;Song, X.",2017,,,0,
4087,Analysis of risk factors for early neurological deterioration in patients with acute middle cerebral artery infarction,"Objective To investigate the risk factors for early neurological deterioration (END) in patients with acute middle cerebral artery infarction. Methods From January 2009 to December 2012, 81 patients with acute middle cerebral artery infarction completed cerebral angiography admitted to the Department of Neurology, Nanjing General Hospital of Nanjing Military Command were enrolled retrospectively. END was defined as that the National Institutes of Health Stroke Scale (NIHSS) score increased >2 or the motor score increased 3= 1 with in 72 h after admission compared with the baseline score on admission. All the patients were divided into either an END group(26 cases) or a non-END group (55 cases) according to whether the occurrence of END. Univariate factor analysis was used to analyze the differences of the clinical data between the two groups. The grade standard of collateral circulation was assessment with the collateral circulation assessment system of the American Society of Interventional and Therapeutic Neuroradiology/ Sociey of Interventional Radiology. Multivariable Logistic regression analysis was used to analyze the risk factors for END after acute middle cerebral artery infarction. Results Compared with the patients in the non-END group, the proportions of age 60 years (65.4% [17/26] vs. 36.4% [20/55] ;χ2 = 5. 992, P = 0. 014), high-sensitivity C-reaetive protein level ≥4.0mg/L (76.9% [20/26] vs. 45.5% [25/55] ;χ2=7.080, P = 0.008) and diabetes (38.5% [10/26] vs. 16.4% [9/55], χ2 = 4. 802, P = 0. 028) in the END group were increased significantly, while the collateral circulation grade was decreased significantly (Z = -3. 253, P <0. 01). Multivariable Logistic regression analysis showed that the age 3:60 years (OR, 3.412, 95%C/ 1.075-10. 824;P =0.037), high-sensitivity C-reactive protein level 3.4. 0 mg/L (OR, 3. 812, 95% C/ 1. 141 -12.740;P=0.030), and collateral circulation grade (OR, 2. 165, 95%CT 1.241 -5. 514;P = 0. 009) were the independent risk factor for END in acute middle cerebral artery infarction. Conclusion The decreased collateral circulation level, age 2: 60 years and high-sensitivity C-reactive protein5= 4. 0 mg/L were the independent risk factors for occurring END in acute middle cerebral artery infarction.",C reactive protein;article;brain angiography;cerebral artery disease;collateral circulation;controlled study;diabetes mellitus;early neurological deterioration;human;major clinical study;mental deterioration;National Institutes of Health Stroke Scale;retrospective study;risk factor,"Guo, H.;Li, H.;Xie, Y.;Shi, W.;Zhao, N.;Liu, X.",2017,,10.3969/j.issn.1672-5921.2017.01.004,0,
4088,Progressive morphometric and cognitive changes in vascular dementia,"Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.","0 (Nootropic Agents);536BQ2JVC7 (Cytidine Diphosphate Choline);Aged;Aged, 80 and over;Anthropometry;Brain/ anatomy & histology/pathology;Cerebral Infarction/ complications/psychology;Cytidine Diphosphate Choline/therapeutic use;Dementia, Vascular/ complications/drug therapy/ psychology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Nootropic Agents/therapeutic use;Severity of Illness Index","Gunstad, J.;Brickman, A. M.;Paul, R. H.;Browndyke, J.;Moser, D. J.;Ott, B. R.;Gordon, N.;Haque, O.;Cohen, R. A.",2005,Mar,,0,4089
4089,Progressive morphometric and cognitive changes in vascular dementia,"Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.","Anthropometry;Brain [anatomy & histology] [pathology];Cerebral Infarction [complications] [psychology];Cytidine Diphosphate Choline [therapeutic use];Dementia, Vascular [complications] [drug therapy] [psychology];Disease Progression;Magnetic Resonance Imaging;Nootropic Agents [therapeutic use];Severity of Illness Index;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Gunstad, J.;Brickman, A. M.;Paul, R. H.;Browndyke, J.;Moser, D. J.;Ott, B. R.;Gordon, N.;Haque, O.;Cohen, R. A.",2005,,10.1016/j.acn.2004.07.001,0,
4090,"C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease","Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n=37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.","Aged;Aged, 80 and over;C-Reactive Protein/ metabolism;Cardiovascular Diseases/ blood/complications/psychology;Cognition Disorders/ blood/complications/psychology;Female;Homocysteine/ blood;Humans;Male;Middle Aged;Neuropsychological Tests;Prospective Studies","Gunstad, J.;Bausserman, L.;Paul, R. H.;Tate, D. F.;Hoth, K.;Poppas, A.;Jefferson, A. L.;Cohen, R. A.",2006,Jun,10.1016/j.jocn.2005.08.010,0,
4091,MRI signal hyperintensities and treatment remission of geriatric depression,"BACKGROUND: White matter abnormalities may interfere with limbic-cortical balance and contribute to chronic depressive syndromes in the elderly. This study sought to clarify the relationship of SH to treatment response. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit greater SH burden than patients who remitted. METHODS: The participants were 42 non-demented individuals with non-psychotic major depression and 25 elderly comparison subjects. After a 2-week single blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. FLAIR sequences were acquired on a 1.5 T scanner and total SH were quantified using a semi-automated thresholding method. RESULTS: The patient sample consisted of 22 depressed patients who achieved remission during the study and 20 depressed patients who remained symptomatic. ANCOVA, with age and gender as covariates, revealed that depressed subjects had greater total SH burden relative to non-depressed controls. Furthermore, patients who failed to remit following escitalopram treatment had significantly greater SH burden than both patients who remitted and elderly comparison subjects, whereas SH burden did not differ between depressed patients who remitted and elderly comparison subjects. LIMITATIONS: Patients were treated with a fixed dose of antidepressants and the index of SH is an overall measure that does not permit examination of the relationship of regional SH to treatment remission. DISCUSSION: SH may contribute to a ""disconnection state"" both conferring vulnerability to and perpetuating late-life depression.","0 (Antidepressive Agents, Second-Generation);0DHU5B8D6V (Citalopram);Aged;Antidepressive Agents, Second-Generation/ therapeutic use;Cerebral Cortex/drug effects/physiopathology;Citalopram/ therapeutic use;Depressive Disorder, Major/ drug therapy/ physiopathology;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Limbic System/drug effects/physiopathology;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales;Single-Blind Method","Gunning-Dixon, F. M.;Walton, M.;Cheng, J.;Acuna, J.;Klimstra, S.;Zimmerman, M. E.;Brickman, A. M.;Hoptman, M. J.;Young, R. C.;Alexopoulos, G. S.",2010,Nov,,0,4092
4092,MRI signal hyperintensities and treatment remission of geriatric depression,"BACKGROUND: White matter abnormalities may interfere with limbic-cortical balance and contribute to chronic depressive syndromes in the elderly. This study sought to clarify the relationship of SH to treatment response. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit greater SH burden than patients who remitted. METHODS: The participants were 42 non-demented individuals with non-psychotic major depression and 25 elderly comparison subjects. After a 2-week single blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. FLAIR sequences were acquired on a 1.5 T scanner and total SH were quantified using a semi-automated thresholding method. RESULTS: The patient sample consisted of 22 depressed patients who achieved remission during the study and 20 depressed patients who remained symptomatic. ANCOVA, with age and gender as covariates, revealed that depressed subjects had greater total SH burden relative to non-depressed controls. Furthermore, patients who failed to remit following escitalopram treatment had significantly greater SH burden than both patients who remitted and elderly comparison subjects, whereas SH burden did not differ between depressed patients who remitted and elderly comparison subjects. LIMITATIONS: Patients were treated with a fixed dose of antidepressants and the index of SH is an overall measure that does not permit examination of the relationship of regional SH to treatment remission. DISCUSSION: SH may contribute to a ""disconnection state"" both conferring vulnerability to and perpetuating late-life depression.","Antidepressive Agents, Second-Generation [therapeutic use];Cerebral Cortex [drug effects] [physiopathology];Citalopram [therapeutic use];Depressive Disorder, Major [drug therapy] [physiopathology];Follow-Up Studies;Image Processing, Computer-Assisted;Limbic System [drug effects] [physiopathology];Magnetic Resonance Imaging;Psychiatric Status Rating Scales;Single-Blind Method;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Gunning-Dixon, F. M.;Walton, M.;Cheng, J.;Acuna, J.;Klimstra, S.;Zimmerman, M. E.;Brickman, A. M.;Hoptman, M. J.;Young, R. C.;Alexopoulos, G. S.",2010,,10.1016/j.jad.2010.04.004,0,
4093,The cognitive correlates of white matter abnormalities in normal aging: A quantitative review,"Cerebral white matter of asymptomatic people frequently exhibits circumscribed areas of hyperintensity on magnetic resonance (MR) images and hypodensity on computed tomography scans. However, behavioral implications of this phenomenon remain unclear. In this meta-analysis, the authors examine cumulative evidence regarding the cognitive sequelae of white matter abnormalities in adults without dementia. The influence of potential moderator variables, such as neuroimaging technique, location of the lesions, rating scale, and demographic characteristics of the sample on the association between the burden of white matter hyperintensities and cognitive performance was also examined. Results indicate that white matter abnormalities observed on MR images are associated with attenuated performance on tasks of processing speed, immediate and delayed memory, executive functions, and indices of global cognitive functioning. There was no significant link between the white matter hyperintensities and psychometric indices of intelligence or fine motor performance.",,"Gunning-Dixon, F. M.;Raz, N.",2000,2000,,0,
4094,Frequency and topography of cerebral microbleeds in dementia with Lewy bodies compared to Alzheimer's disease,"AIM: To determine the frequency and topographic distribution of cerebral microbleeds (CMBs) in dementia with Lewy bodies (DLB) in comparison to CMBs in Alzheimer disease dementia (AD). METHODS: Consecutive probable DLB (n = 23) patients who underwent 3-T T2* weighted gradient-recalled-echo MRI, and age and gender matched probable Alzheimer's disease patients (n = 46) were compared for the frequency and location of CMBs. RESULTS: The frequency of one or more CMBs was similar among patients with DLB (30%) and AD (24%). Highest densities of CMBs were found in the occipital lobes of patients with both DLB and AD. Patients with AD had greater densities of CMBs in the parietal, temporal lobes and infratentorial regions compared to DLB (p < 0.05). CONCLUSION: CMBs are as common in patients with DLB as in patients with AD, with highest densities observed in the occipital lobes, suggesting common pathophysiologic mechanisms underlying CMBs in both diseases.",Alzheimer disease;Cerebral amyloid angiopathy;Cerebral microbleeds;Dementia with Lewy bodies;T2* weighted gradient-recalled-echo MRI,"Gungor, I.;Sarro, L.;Graff-Radford, J.;Zuk, S. M.;Tosakulwong, N.;Przybelski, S. A.;Lesnick, T.;Boeve, B. F.;Ferman, T. J.;Smith, G. E.;Knopman, D. S.;Filippi, M.;Petersen, R. C.;Jack, C. R., Jr.;Kantarci, K.",2015,Sep,10.1016/j.parkreldis.2015.07.008,0,
4095,ADC histograms from routine DWI for longitudinal studies in cerebral small vessel disease: a field study in CADASIL,"Diffusion tensor imaging (DTI) histogram metrics are correlated with clinical parameters in cerebral small vessel diseases (cSVD). Whether ADC histogram parameters derived from simple diffusion weighted imaging (DWI) can provide relevant markers for long term studies of cSVD remains unknown. CADASIL patients were evaluated by DWI and DTI in a large cohort study over a 6-year period. ADC histogram parameters were compared to those derived from mean diffusivity (MD) histograms in 280 patients using intra-class correlation and Bland-Altman plots. Impact of image corrections applied to ADC maps was assessed and a mixed effect model was used for analyzing the effects of scanner upgrades. The results showed that ADC histogram parameters are strongly correlated to MD histogram parameters and that image corrections have only limited influence on these results. Unexpectedly, scanner upgrades were found to have major effects on diffusion measures with DWI or DTI that can be even larger than those related to patients' characteristics. These data support that ADC histograms from daily used DWI can provide relevant parameters for assessing cSVD, but the variability related to scanner upgrades as regularly performed in clinical centers should be determined precisely for longitudinal and multicentric studies using diffusion MRI in cSVD.","CADASIL/ diagnosis;Cohort Studies;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Male;Probability","Gunda, B.;Porcher, R.;Duering, M.;Guichard, J. P.;Mawet, J.;Jouvent, E.;Dichgans, M.;Chabriat, H.",2014,,10.1371/journal.pone.0097173,0,
4096,Effects of gender on the phenotype of CADASIL,"BACKGROUND AND PURPOSE: In the general population, migraine, cerebrovascular diseases, and vascular dementia differ in many aspects between men and women. CADASIL is considered a unique model to investigate migraine with aura, stroke, and dementia related to ischemic small vessel disease. This study aims to evaluate the effect of gender on the main clinical and neuroimaging characteristics of CADASIL. METHODS: Cross-sectional data from 313 CADASIL patients including various clinical and cognitive scores and MRI parameters were compared between men and women, and between those younger and older than the median age of the population corresponding to the usual age of menopause (51 years). RESULTS: At younger than 51 years, migraine with aura was 50% more prevalent in women and stroke was 75% more prevalent in men. After the fifth decade, men had higher National Institutes of Health Stroke Scale and Rankin scores than women and more severe executive dysfunction, although global cognitive scores were similar. Age at first stroke, the number of stroke events, and the prevalence of dementia and psychiatric symptoms did not differ between men and women. Brain volume was lower in men with a trend for a larger volume of lacunar infarcts. CONCLUSIONS: In CADASIL, migraine with aura is more frequent in women and stroke is more frequent in men before the age of menopause. This difference seems to vanish after this age limit but may result in a higher degree of cognitive impairment and cerebral atrophy in men at the late stage of the disease. The presumable role of ovarian hormones in these gender-related differences remains to be explored.",Adult;Age Factors;Brain Ischemia/*genetics/physiopathology/psychology;CADASIL/*diagnosis/genetics/physiopathology/psychology;Cross-Sectional Studies;Executive Function;Female;Humans;Male;Middle Aged;Migraine with Aura/*genetics/physiopathology/psychology;*Phenotype;Sex Factors;Stroke/*genetics/physiopathology/psychology,"Gunda, B.;Herve, D.;Godin, O.;Bruno, M.;Reyes, S.;Alili, N.;Opherk, C.;Jouvent, E.;During, M.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2012,Jan,10.1161/strokeaha.111.631028,0,
4097,"Distribution and binding of (18)F-labeled and (125)I- labeled analogues of ACI-80, a prospective molecular imaging biomarker of disease: A whole hemisphere post mortem autoradiography study in human brains obtained from Alzheimer's disease patients","One of the major pathological landmarks of Alzheimer's disease and other neurodegenerative diseases is the presence of amyloid deposits in the brain. The early non-invasive visualization of amyloid is a major objective of recent diagnostic neuroimaging approaches, including positron emission tomography (PET), with an eye on follow-up of disease progression and/or therapy efficacy. The development of molecular imaging biomarkers with binding affinity to amyloid in the brain is therefore in the forefront of imaging biomarker and radiochemistry research. Recently, a dodecamer peptide (amino acid sequence = QSHYRHISPAQV; denominated D1 or ACI-80) was identified as a prospective ligand candidate, binding with high ex vivo affinity to L-Aβ-amyloid (K (d): 0.4 μM). In order to assess the ligand's capacity to visualize amyloid in Alzheimer's disease (AD), two (125)I labeled and three (18)F labeled analogues of the peptide were synthesized and tested in post mortem human autoradiography experiments using whole hemisphere brain slices obtained from deceased AD patients and age matched control subjects. The (18)F-labeled radioligands showed more promising visualization capacity of amyloid that the (125)I-labeled radioligands. In the case of each (18)F radioligands the grey matter uptake in the AD brains was significantly higher than that in control brains. Furthermore, the grey matter: white matter uptake ratio was over ∼2, the difference being significant for each (18)F-radioligands. The regional distribution of the uptake of the various radioligands systematically shows a congruent pattern between the high uptake regions and spots in the autoradiographic images and the disease specific signals obtained in adjacent or identical brain slices labeled with histological, immunohistochemical or autoradiographic stains for amyloid deposits or activated astrocytes. The present data, using post mortem human brain autoradiography in whole hemisphere human brains obtained from deceased AD patients and age matched control subjects, support the visualization capacity of the radiolabeled ACI-80 analogues of amyloid deposits in the human brain. Further studies are warranted to explore the usefulness of the (18)F-labeled analogues as in vivo molecular imaging biomarkers in diagnostic PET studies. © 2011 Elsevier Ltd. All rights reserved.",,"Gulyás, B.;Spenger, C.;Beliczai, Z.;Gulya, K.;Kása, P.;Jahan, M.;Jia, Z.;Weber, U.;Pfeifer, A.;Muhs, A.;Willbold, D.;Halldin, C.",2012,January,,0,
4098,"Activated MAO-B in the brain of Alzheimer patients, demonstrated by 11C -L-deprenyl using whole hemisphere autoradiography","In the human brain the monoaminooxidase-B enzyme or MAO-B is highly abundant in astrocytes. As astrocyte activity and, consequently, the activity of the MAO-B enzyme, is up-regulated in neuroinflammatory processes, radiolabelled analogues of deprenyl may serve as an imaging biomarker in neuroinflammation and neurodegeneration, including Alzheimer's disease. In the present study [(11)C]-L-deprenyl, the PET radioligand version of L-deprenyl or selegiline(R), a selective irreversible MAO-B inhibitor was used in whole hemisphere autoradiographic experiments in human brain sections in order to test the radioligand's binding to the MAO-B enzyme in human brain tissue, with an eye on exploring the radioligand's applicability as a molecular imaging biomarker in human PET studies, with special regard to diagnostic detection of reactive astrogliosis. Whole hemisphere brain sections obtained from Alzheimer patients and from age matched control subjects were examined. In control brains the binding of [(11)C]-L-deprenyl was the highest in the hippocampus, in the basal ganglia, the thalamus, the substantia nigra, the corpus geniculatum laterale, the nucleus accumbens and the periventricular grey matter. In Alzheimer brains significantly higher binding was observed in the temporal lobes and the white matter. Furthermore, in the Alzheimer brains in the hippocampus, temporal lobe and white matter the binding negatively correlated with Braak stages. The highest binding was observed in Braak I-II, whereas it decreased with increasing Braak grades. The increased regional binding in Alzheimer brains coincided with the presence of an increased number of activated astrocytes, as demonstrated by correlative immunohistochemical studies with GFAP in adjacent brain slices. Deprenyl itself as well as the MAO-B antagonist rasagiline did effectively block the binding of the radioligand, whereas the MAO-A antagonist pirlindole did not affect it. Compounds with high affinity for the PBR system did not block the radioligand binding either, providing evidence for the specificity of [(11)C]-L-deprenyl for the MAO-B enzyme. In conclusion, the present observations indicate that [(11)C]-L-deprenyl may be a promising and selective imaging biomarker of increased MAO-B activity in the human brain and can therefore serve as a prospective PET tracer targeting neuroinflammation and neurodegeneration.","Aged;Aged, 80 and over;Alzheimer Disease/ enzymology/radionuclide imaging;Astrocytes/metabolism;Autoradiography;Brain/ enzymology/radionuclide imaging;Disease Progression;Female;Gliosis/enzymology/radionuclide imaging;HLA Antigens/metabolism;Humans;Immunohistochemistry;Isotope Labeling;Male;Microglia/metabolism;Middle Aged;Monoamine Oxidase/ metabolism;Monoamine Oxidase Inhibitors;Neuritis/enzymology;Radiopharmaceuticals/chemical synthesis;Selegiline;Substrate Specificity;Up-Regulation/genetics","Gulyas, B.;Pavlova, E.;Kasa, P.;Gulya, K.;Bakota, L.;Varszegi, S.;Keller, E.;Horvath, M. C.;Nag, S.;Hermecz, I.;Magyar, K.;Halldin, C.",2011,Jan,10.1016/j.neuint.2010.10.013,0,
4099,A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system,"The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18 kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain. © 2008 Elsevier Ltd. All rights reserved.",,"Gulyás, B.;Makkai, B.;Kása, P.;Gulya, K.;Bakota, L.;Várszegi, S.;Beliczai, Z.;Andersson, J.;Csiba, L.;Thiele, A.;Dyrks, T.;Suhara, T.;Suzuki, K.;Higuchi, M.;Halldin, C.",2009,January,,0,
4100,Neurobrucellosis presenting as leukoencephalopathy and deafness,"Neurological involvement of the central nervous system in brucellosis is uncommon. Sensorineural hearing loss is a rare complication of neurobrucellosis, which has not attracted enough attention among the known manifestations. A 50-year-old male presented with headache, deafness and deterioration in cognitive functions. The presence of diffuse white matter changes on brain magnetic resonance imaging and serum and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. The differential diagnosis of diffuse white matter diseases is constantly expanding. In the background of fever, deafness, demential symptoms, cognitive impairment, and extensive white matter disease, neurobrucellosis should be considered in the diagnosis.",,"Güleç, F.;Uysal, H. A.;Zorlu, Y.",2011,2011,,0,
4101,Cryptogenic multi-infarcts and cortico-subcortical dementia in a young adult,"Introduction: Etiology of stroke and dementia in young adults are challenging clinical problems, and these diseases often have devastating consequences. We present a case where a final etiologic diagnosis is not possible, in spite of an exhaustive study. Case Report: A 34-year-old man presented with a 5-year history of transient neurological deficits. Examination disclosed a cortico-subcortical dementia, but no other deficits. Laboratory evaluation was unremarkable, including the basic vascular study, homocystein, immunologic study, ACE, serology for Lyme, syphilis and HIV, tests for mitochondrial cytopathy, CADASIL and Fabry's disease, and CSF study. Prothrombotic study was normal except for a heterozygous mutation for factor V Leiden and for methylene tetrahydrofolate reductase. Cardiac exams (electrocardiogram, transesophagic echocardiography and 24 h-ECG) were normal. Cervical and transcranial duplex ultrasound and magnetic resonance angiography (MRA)-were normal, except for a hypoplasic right vertebral artery. Brain magnetic resonance imaging revealed corticosubcortical atrophy and multiple infarcts. The patient was prescribed antiplatelet and statin therapy, and is presently clinically stabilized after 3 years of follow-up, scoring 2 in modified Rankin scale. Discussion: Differential diagnosis of young onset vascular dementia is wide, including a number of rare sporadic and hereditary diseases. Although our case has a heterozygotic mutation for factor V Leiden, this might not explain the whole clinical picture; furthermore, there is no history of other vascular events, as venous thrombosis. An extensive investigation did not lead to a final etiological diagnosis. Nevertheless, even in these cases prevention with antiplatelet and statin might lead to clinical stabilization. © 2007 Elsevier B.V. All rights reserved.",,"Guimarães, J.;Fonseca, R.;Azevedo, E.",2007,15,,0,
4102,"An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.",cysteine;glycine;Notch3 receptor;osmium;threonine;adult;amino terminal sequence;article;basement membrane;brain infarction;brain ischemia;CADASIL;case report;clinical feature;codon;cognitive defect;dementia;exon;female;gene mutation;genetic analysis;histopathology;hospital admission;human;Italy;medical literature;migraine;missense mutation;nuclear magnetic resonance imaging;nucleotide sequence;pathophysiology;pseudobulbar palsy;pyramidal sign;recurrent disease;sequence analysis;skin capillary;cerebrovascular accident;transient ischemic attack;ultrastructure,"Guidetti, D.;Casali, B.;Mazzei, R. L.;Cenacchi, G.;Di Berti, G.;Zuccoli, G.;Nicoli, D.;Conforti, F. L.;Sprovieri, T.;Pasquinelli, G.;Brini, M.",2004,,,0,
4103,Prevalence and characteristics of migraine in CADASIL,"Background and objective Migraine with aura (MA) is a major symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We assessed the spectrum of migraine symptoms and their potential correlates in a large prospective cohort of CADASIL individuals. Methods A standardized questionnaire was used in 378 CADASIL patients for assessing headache symptoms, trigger factors, age at first attack, frequency of attacks and associated symptoms. MRI lesions and brain atrophy were quantified. Results A total of 54.5% of individuals had a history of migraine, mostly MA in 84% of them; 62.4% of individuals with MA were women and age at onset of MA was lower in women than in men. Atypical aura symptoms were experienced by 59.3% of individuals with MA, and for 19.7% of patients with MA the aura was never accompanied by headache. MA was the inaugural manifestation in 41% of symptomatic patients and an isolated symptom in 12.1% of individuals. Slightly higher MMSE and MDRS scores and lower Rankin score were detected in the MA group. Conclusion MA is observed in almost half of all CADASIL patients. Atypical aura symptoms are reported by more than one in two of them. MA is often inaugural, can remain isolated and is not associated with the severity of the disorder.",adult;aged;article;brain atrophy;CADASIL;cohort analysis;controlled study;dementia assessment;disease association;disease severity;female;human;limit of quantitation;major clinical study;male;Mattis Dementia Rating scale;migraine with aura;migraine without aura;Mini Mental State Examination;nuclear magnetic resonance imaging;prevalence;prospective study;questionnaire;Rankin scale,"Guey, S.;Mawet, J.;Hervé, D.;Duering, M.;Godin, O.;Jouvent, E.;Opherk, C.;Alili, N.;Dichgans, M.;Chabriat, H.",2016,,10.1177/0333102415620909,0,
4104,Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer's disease,"Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain disease-causing mutations are thought to exist. We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family with a complex history of neurological and immunological disorders and identified a mutation in NOTCH3 (p.R1231C), previously described as causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Complete screening of NOTCH3 in a cohort of 95 early onset AD cases and 95 controls did not reveal any additional pathogenic mutations. Although the complex history of disease in this family precluded us to establish segregation of the mutation found with disease, our results show that exome sequencing is a rapid, cost-effective and comprehensive tool to detect genetic mutations, allowing for the identification of unexpected genetic causes of clinical phenotypes. As etiological based therapeutics become more common, this method will be key in diagnosing and treating disease. © 2012 Elsevier Inc.",donepezil;levodopa;tizanidine;adult;aged;Alzheimer disease;article;brain atrophy;consanguinity;controlled study;drug dose reduction;drug withdrawal;dystonia;electromyogram;exome;family;female;gene;gene mutation;gene sequence;genetic screening;hallucination;human;major clinical study;male;memory disorder;Mini Mental State Examination;NOTCH3 gene;nuclear magnetic resonance imaging;nucleotide sequence;pathogenesis;physiotherapy;priority journal;psychosis;Turkey (republic),"Guerreiro, R. J.;Lohmann, E.;Kinsella, E.;Brás, J. M.;Luu, N.;Gurunlian, N.;Dursun, B.;Bilgic, B.;Santana, I.;Hanagasi, H.;Gurvit, H.;Gibbs, J. R.;Oliveira, C.;Emre, M.;Singleton, A.",2012,,,0,
4105,Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement,"Objective: To identify new genes and risk factors associated with frontotemporal dementia (FTD). Several genes and loci have been associated with different forms of FTD, but a large number of families with dementia do not harbor mutations in these genes. Design: Whole-exome sequencing and whole-genome genotyping were performed in all patients. Genetic variants obtained from whole-exome sequencing were integrated with the data obtained from whole-genome genotyping. Setting: Database of the Behavioral Neurology OutpatientClinic of theDepartment of Neurology, Istanbul Faculty of Medicine, Istanbul, Turkey. Patients: Forty-four Turkish patients with an FTDlike clinical diagnosis were included in the study. Relatives were screened when appropriate. Main Outcome Measure: Mutations in the triggering receptor expressed on myeloid cells 2 gene (TREM2). Results: In 3 probands with FTD-like disease, we identified different homozygous mutations in TREM2 that had previously been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). None of these 3 patients had a typical clinical presentation of PLOSL: they presented with behavioral change and subsequent cognitive impairment and motor features but without any bone cysts or boneassociated phenotypes. Imaging showed white matter abnormalities as well as frontal atrophy in all 3 patients. Conclusions: Our results show that TREM2 is responsible for an unexpectedly high number of dementia cases in our cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded. Even for complex syndromes such as dementia, exome sequencing has proven to be a rapid and cost-effective tool to identify genetic mutations, allowing for the association of clinical phenotypes with unexpected molecular underpinnings. © 2013 American Medical Association.",,"Guerreiro, R. J.;Lohmann, E.;Brás, J. M.;Gibbs, J. R.;Rohrer, J. D.;Gurunlian, N.;Dursun, B.;Bilgic, B.;Hanagasi, H.;Gurvit, H.;Emre, M.;Singleton, A.;Hardy, J.",2013,January,,0,
4106,White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70-year-olds followed over 10 years,"Background and purpose: A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population. Methods: Whether WMLs and cortical atrophy on computed tomography predict dementia and depression was investigated in a population-based sample of 70-year-olds (n = 380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini-Mental State Examination score below 26 at baseline in 2000-2001. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary outcomes included dementia and major depression at 10-year follow-up. Results: Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.23-12.76] and temporal lobe atrophy (OR 2.93, 95% CI 1.13-7.60) predicted dementia during a 10-year follow-up independently of major depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25-11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even after controlling for incident dementia. Conclusion: White matter lesions and temporal lobe atrophy preceded 10-year incidence of both dementia and depression in 70-year-olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults.",antidepressant agent;aged;article;brain cortex atrophy;cerebrovascular accident;computed tomography scanner;computer assisted tomography;dementia;disease association;DSM-5;DSM-III-R;female;follow up;gerontopsychiatry;human;incidence;major clinical study;major depression;male;medical history;Mini Mental State Examination;neuroimaging;outcome assessment;population research;priority journal;psychopharmacotherapy;temporal lobe atrophy;white matter lesion,"Gudmundsson, P.;Olesen, P. J.;Simoni, M.;Pantoni, L.;Östling, S.;Kern, S.;Guo, X.;Skoog, I.",2015,,,0,
4107,"Migraine, depression, and brain volume: The AGES-Reykjavik study","Objective: To examine the joint association of migraine headache and major depressive disorder on brain volume in older persons without dementia. Methods: Participants (n = 4,296, 58% women) from the population-based Age, Gene/Environment Susceptibility-Reykjavik Study were assessed for migraine headache in 1967-1991 (age 51 years [range 33-65]) according to modified International Classification of Headache Disorders-II criteria. In 2002-2006 (age 76 years [range 66-96]), lifetime history of major depressive disorder (depression) was diagnosed according to DSM-IV criteria, and full-brain MRI was acquired, which was computer postprocessed into total brain volume (TBV) (gray matter [GM], white matter [WM], white matter hyperintensities) and CSF volume for each study subject. We compared brain tissue volumes by headache categories with or without depression using linear regression, adjusting for intracranial volume and other factors. Results: Compared with the reference group (no headache, no depression) TBV and WM and GM volumes were smaller in those with both migraine and depression (TBV -19.2 mL, 95% confidence interval [CI] -35.3, -3.1, p = 0.02; WM -12.8 mL, CI -21.3, -4.3, p = 0.003; GM -13.0 mL, CI -26.0, 0.1, p = 0.05) but not for those with migraine alone (TBV 0.4 mL, WM 0.2 mL, GM 0.6 mL) or depression alone (TBV -3.9 mL, WM -0.9 mL, GM -2.9 mL). Conclusions: Reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes than having one or neither of these conditions. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae. Nonetheless, the number of subjects in the current study is relatively small and these findings need to be confirmed in future studies. © 2013 American Academy of Neurology.",adult;age distribution;aged;article;brain size;brain tissue volume;cerebrospinal fluid volume;controlled study;dementia;disease association;disease classification;DSM-IV;female;genotype environment interaction;gray matter;headache;human;image analysis;international classification of headache disorder ii;major clinical study;major depression;male;medical history;migraine;nervous system parameters;nuclear magnetic resonance imaging;phenotype;population research;priority journal;total brain volume;white matter;white matter hyperintensity,"Gudmundsson, L. S.;Scher, A. I.;Sigurdsson, S.;Geerlings, M. I.;Vidal, J. S.;Eiriksdottir, G.;Garcia, M. I.;Harris, T. B.;Kjartansson, O.;Aspelund, T.;Van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2013,,,0,
4108,Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE),"The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.","Aged;Blood Volume;Cerebrovascular Circulation;Dementia, Vascular/ physiopathology;Female;Humans;Magnetic Resonance Imaging;Male","Guckel, F. J.;Brix, G.;Hennerici, M.;Lucht, R.;Ueltzhoffer, C.;Neff, W.",2007,Oct,10.1007/s00330-007-0617-y,0,
4109,The syndrome of bilateral paramedian thalamic infarction,"Bilateral anterior paramedian thalamic infarction resulting from occlusion of a bilaterally distributed thalamosubthalamic paramedian artery was demonstrated on CT in two patients. Patient 1 presented with a transient coma followed by asterixis, hypersomnia, vertical gaze disturbances, profound Korsakoff amnesic syndrome, and a subcortical dementia. Patient 2, with a predominantly right-sided thalamic infarct, showed good recovery from amnesia and vertical gaze disturbances. However, patient 1 remained with severe amnesia and mild subcortical dementia at follow-up 1 year later. These and similar reported cases constitute a lacunar syndrome with characteristic clinical and CT features.",mersalyl;amnesia;brain infarction;case report;central nervous system;coma;computer analysis;computer assisted tomography;diagnosis;flapping tremor;human;hypersomnia;lacuna;patient;psychologic test;thalamus,"Guberman, A.;Stuss, D.",1983,,,0,
4110,Cerebral hemorrhage in CADASIL,"Introduction CADASIL is a hereditary disease of the cerebral small blood vessels. We describe the case of a patient with diagnosis of CADASIL and intracerebral hemorrhage. Clinical case A 47-year-old hypertensive male patient treated with antithrombotic agents, who was diagnosed with CADASIL by skin biopsy and admitted for sudden intense headache. The MRI showed left occipital intracerebral hemorrhage. Conclusion In patients diagnosed with CADASIL a positive echo-time for microbleeds could avoid the use of antithrombotic agents given the high risk of ICH, thus avoiding adding damage to a disease that has no specific treatment to date.",anticoagulant agent;adult;article;brain hemorrhage;CADASIL;case report;disease severity;headache;hospital admission;human;human tissue;hypertension;male;medical history;nuclear magnetic resonance imaging;skin biopsy,"Guarnaschelli, M.;Sotelo, A.",2017,,10.1016/j.neuarg.2016.05.001,0,
4111,Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population,"The aim of this investigation was to determine whether circulating inflammatory biomarkers c-reactive protein (CRP), interleukin-6 (IL6), and alpha 1-antichymotrypsin (ACT) were related to structural brain measures assessed by magnetic resonance imaging (MRI). High-resolution structural MRI was collected on 680 non-demented elderly (mean age 80.1years) participants of a community-based, multiethnic cohort. Approximately three quarters of these participants also had peripheral inflammatory biomarkers (CRP, IL6, and ACT) measured using ELISA. Structural measures including brain volumes and cortical thickness (with both global and regional measures) were derived from MRI scans, and repeated MRI measures were obtained after 4.5years. Mean fractional anisotropy was used as the indicator of white matter integrity assessed with diffusion tensor imaging. We examined the association of inflammatory biomarkers with brain volume, cortical thickness, and white matter integrity using regression models adjusted for age, gender, ethnicity, education, APOE genotype, and intracranial volume. A doubling in CRP (b=-2.48, p=0.002) was associated with a smaller total gray matter volume, equivalent to approximately 1.5years of aging. A doubling in IL6 was associated with smaller total brain volume (b=-14.96, p<0.0001), equivalent to approximately 9years of aging. Higher IL6 was also associated with smaller gray matter (b=-6.52, p=0.002) and white matter volumes (b=-7.47, p=0.004). The volumes of most cortical regions including frontal, occipital, parietal, temporal, as well as subcortical regions including pallidum and thalamus were associated with IL6. In a model additionally adjusted for depression, vascular factors, BMI, and smoking status, the association between IL6 and brain volumes remained, and a doubling in ACT was marginally associated with 0.054 (p=0.001) millimeter thinner mean cortical thickness, equivalent to that of approximately 2.7years of aging. None of the biomarkers was associated with mean fractional anisotropy or longitudinal change of brain volumes and thickness. Among older adults, increased circulating inflammatory biomarkers were associated with smaller brain volume and cortical thickness but not the white matter tract integrity. Our preliminary findings suggest that peripheral inflammatory processes may be involved in the brain atrophy in the elderly.",Alpha 1-antichymotrypsin;Brain atrophy;Brain morphometry;C-reactive protein;Cortical thickness;Interleukin-6;Magnetic resonance imaging;Neuroepidemiology,"Gu, Y.;Vorburger, R.;Scarmeas, N.;Luchsinger, J. A.;Manly, J. J.;Schupf, N.;Mayeux, R.;Brickman, A. M.",2017,Oct,,0,
4112,Alcohol intake and brain structure in a multiethnic elderly cohort,"BACKGROUND & AIMS: Evidence suggests that consuming light-to-moderate amounts of alcohol reduces the risk of dementia and is associated better cognitive function and less cardiovascular disease, relative to those consuming no or heavy alcohol. There are only minimal data on the association between alcohol and brain magnetic resonance imaging (MRI) markers. This study aimed to examine the association between alcohol and brain structure measured with MRI. METHODS: In this cross-sectional study, high-resolution structural MRI was collected on 589 multi-ethnic community residents of New York aged >/=65 with available alcohol intake assessments via a food frequency questionnaire. Total brain volume (TBV), white matter hyperintensity volume (WMHV), and presence of infarcts were derived from MRI scans with established methods. We examined the association of alcohol intake with these imaging markers using regression models adjusted for demographic, clinical, and vascular risk factors. RESULTS: Compared to non-drinking, light-to-moderate total alcohol (b = 0.007, p = 0.04) or wine (b = 0.008, p = 0.05) intake, but not beer or liquor intake, was associated with larger TBV. Further analysis showed a dose-response association between alcohol (p-trend = 0.03) or wine (p-trend = 0.006) and TBV. Overall, alcohol intake was not associated with WMHV or brain infarcts. CONCLUSIONS: Our study suggests that among older adults in the community, light-to-moderate alcohol intake, in particular wine, is associated with larger TBV. These findings suggest that light to moderate alcohol consumption is potentially beneficial for brain aging, but replication is needed.","Aged;Aged, 80 and over;Alcohol Drinking/ blood;Beer;Brain/anatomy & histology/ drug effects;Cognition/drug effects;Cross-Sectional Studies;Dementia/prevention & control;Dose-Response Relationship, Drug;Ethnic Groups;Female;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Risk Factors;Surveys and Questionnaires;Wine","Gu, Y.;Scarmeas, N.;Short, E. E.;Luchsinger, J. A.;DeCarli, C.;Stern, Y.;Manly, J. J.;Schupf, N.;Mayeux, R.;Brickman, A. M.",2014,Aug,10.1016/j.clnu.2013.08.004,0,
4113,Mediterranean diet and brain structure in a multiethnic elderly cohort,"OBJECTIVE: To determine whether higher adherence to a Mediterranean-type diet (MeDi) is related with larger MRI-measured brain volume or cortical thickness. METHODS: In this cross-sectional study, high-resolution structural MRI was collected on 674 elderly (mean age 80.1 years) adults without dementia who participated in a community-based, multiethnic cohort. Dietary information was collected via a food frequency questionnaire. Total brain volume (TBV), total gray matter volume (TGMV), total white matter volume (TWMV), mean cortical thickness (mCT), and regional volume or CT were derived from MRI scans using FreeSurfer program. We examined the association of MeDi (scored as 0-9) and individual food groups with brain volume and thickness using regression models adjusted for age, sex, ethnicity, education, body mass index, diabetes, and cognition. RESULTS: Compared to lower MeDi adherence (0-4), higher adherence (5-9) was associated with 13.11 (p = 0.007), 5.00 (p = 0.05), and 6.41 (p = 0.05) milliliter larger TBV, TGMV, and TWMV, respectively. Higher fish (b = 7.06, p = 0.006) and lower meat (b = 8.42, p = 0.002) intakes were associated with larger TGMV. Lower meat intake was also associated with larger TBV (b = 12.20, p = 0.02). Higher fish intake was associated with 0.019 mm (p = 0.03) larger mCT. Volumes of cingulate cortex, parietal lobe, temporal lobe, and hippocampus and CT of the superior-frontal region were associated with the dietary factors. CONCLUSIONS: Among older adults, MeDi adherence was associated with less brain atrophy, with an effect similar to 5 years of aging. Higher fish and lower meat intake might be the 2 key food elements that contribute to the benefits of MeDi on brain structure.","Aged;Aged, 80 and over;Brain/*anatomy & histology/*metabolism;Cohort Studies;Cross-Sectional Studies;*Diet Records;Diet, Mediterranean/*ethnology;Ethnic Groups/*ethnology;Female;Humans;Magnetic Resonance Imaging/trends;Male;Organ Size/physiology;Prospective Studies","Gu, Y.;Brickman, A. M.;Stern, Y.;Habeck, C. G.;Razlighi, Q. R.;Luchsinger, J. A.;Manly, J. J.;Schupf, N.;Mayeux, R.;Scarmeas, N.",2015,Nov 17,10.1212/wnl.0000000000002121,0,
4114,Key neuroanatomical structures for post-stroke cognitive impairment,"The neuroanatomical substrate of vascular cognitive impairment (VCI) has traditionally included the subcortex of the brain, especially sub-frontal white matter circuits, strategic areas of single infarction that may mediate cognitive impairment such as the dominant thalamus or angular gyrus, and the left hemisphere, and bilateral brain infarcts or volume-driven cortical-subcortical infarctions reaching a critical threshold of tissue loss or injury. We provide an update on the neuroanatomical substrates of VCI and emphasize the following structures or areas: (1) new concepts in relation to hippocampal involvement in VCI based on neuropathological and MRI studies of microinfarcts and the role of traditional cardiovascular risk factors in possibly mediating or potentiating cognitive impairment; (2) advances in our understanding of cerebral microbleeds; and (3) an update on white matter hyperintensities and small vessel disease. © Springer Science+Business Media, LLC 2012.",Alzheimer disease;article;brain atrophy;brain hemorrhage;brain infarction;brain size;cardiovascular risk;cerebrovascular accident;cognitive defect;degenerative disease;dementia;episodic memory;hippocampus;human;memory disorder;Mini Mental State Examination;neuroanatomy;neuropathology;neuropsychological test;nuclear magnetic resonance imaging;vascular cognitive impairment;white matter lesion,"Grysiewicz, R.;Gorelick, P. B.",2012,,,0,
4115,Improved prediction of Alzheimer's disease with longitudinal white matter/gray matter contrast changes,"Brain morphometry measures derived from magnetic resonance imaging (MRI) are important biomarkers for Alzheimer's disease (AD). The objective of the present study was to test whether we could improve morphometry-based detection and prediction of disease state by use of white matter/gray matter (WM/GM) signal intensity contrast obtained from conventional MRI scans. We hypothesized that including WM/GM contrast change along with measures of atrophy in the entorhinal cortex and the hippocampi would yield better classification of AD patients, and more accurate prediction of early disease progression. T1 -weighted MRI scans from two sessions approximately 2 years apart from 78 participants with AD (Clinical Dementia Rating (CDR) = 0.5-2) and 71 age-matched controls were used to calculate annual change rates. Results showed that WM/GM contrast decay was larger in AD compared with controls in the medial temporal lobes. For the discrimination between AD and controls, entorhinal WM/GM contrast decay contributed significantly when included together with decrease in entorhinal cortical thickness and hippocampal volume, and increased the area under the curve to 0.79 compared with 0.75 when using the two morphometric variables only. Independent effects of WM/GM contrast decay and improved classification were also observed for the CDR-based subgroups, including participants converting from either a non-AD status to very mild AD, or from very mild to mild AD. Thus, WM/GM contrast decay increased diagnostic accuracy beyond what was obtained by well-validated morphometric measures alone. The findings suggest that signal intensity properties constitute a sensitive biomarker for cerebral degeneration in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ pathology/psychology;Area Under Curve;Atrophy;Brain/ pathology;Cerebral Cortex/pathology;Educational Status;Entorhinal Cortex/pathology;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;ROC Curve;Reproducibility of Results;Socioeconomic Factors","Grydeland, H.;Westlye, L. T.;Walhovd, K. B.;Fjell, A. M.",2013,Nov,10.1002/hbm.22103,0,
4116,Novel ophthalmic pathology in an autopsy case of autosomal dominant retinal vasculopathy with cerebral leukodystrophy,"Autosomal dominant retinocerebral vasculopathy with cerebral leukodystrophy (RVCL) is a rare neurovascular syndrome causing retinal and central nervous system vasculopathy often recognized as contrast-enhancing white matter changes or pseudotumors on imaging. Heterozygous frameshift mutations in the 3-prime repair exonuclease 1 gene have been identified in families affected by RVCL. Variable light microscopic findings and a characteristic ultrastructural appearance of the vasculature in the brain have been reported. Description of the ophthalmic histopathology is exceedingly rare. Here, we report previously undescribed bilateral eye findings in a patient diagnosed with RVCL. The ophthalmic pathology includes thickening and reduplication of the retinal capillary basal lamina demonstrated by electron microscopy. These findings expand what is known about this disease and help further delineate its phenotype. © 2011 Lippincott Williams & Wilkins, Inc.",,"Gruver, A. M.;Schoenfield, L.;Coleman, J. F.;Hajj-Ali, R.;Rodriguez, E. R.;Tan, C. D.",2011,March,,0,
4117,Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy,"There are reports of weight loss and low body mass index (BMI) in patients with AD. The mesial temporal cortex (MTC) is involved in feeding behavior and memory and is preferentially involved in AD. We studied 74 subjects, including 58 AD patients and 16 control subjects, to determine whether BMI is associated with atrophy of the MTC or other brain regions. We used MRI morphometric analysis to provide measures of regional brain atrophy. AD patients had significant brain atrophy in all measured brain regions, except the white matter, compared with normal control subjects. The MTC was the only brain region significantly associated with BMI in AD patients (r = 0.39, p = 0.003). Multiple-regression analysis indicated that addition of brain regions other than the MTC to the model did not significantly add to the prediction of BMI. We conclude that low BMI correlates best and specifically with MTC atrophy. This finding supports a connection between limbic system damage and low body weight in AD.",aged;Alzheimer disease;article;body mass;brain cortex atrophy;brain size;clinical protocol;controlled study;feeding behavior;female;human;limbic system;major clinical study;male;memory;morphometrics;nuclear magnetic resonance imaging;priority journal;temporal cortex;weight reduction,"Grundman, M.;Corey-Bloom, J.;Jernigan, T.;Archibald, S.;Thal, L. J.",1996,,,0,
4118,Disruption of large-scale neural networks in non-fluent/agrammatic variant primary progressive aphasia associated with frontotemporal degeneration pathology,"Non-fluent/agrammatic primary progressive aphasia (naPPA) is a progressive neurodegenerative condition most prominently associated with slowed, effortful speech. A clinical imaging marker of naPPA is disease centered in the left inferior frontal lobe. We used multimodal imaging to assess large-scale neural networks underlying effortful expression in 15 patients with sporadic naPPA due to frontotemporal lobar degeneration (FTLD) spectrum pathology. Effortful speech in these patients is related in part to impaired grammatical processing, and to phonologic speech errors. Gray matter (GM) imaging shows frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Diffusion tensor imaging reveals reduced fractional anisotropy in several white matter (WM) tracts mediating projections between left frontal and other GM regions. Regression analyses suggest disruption of three large-scale GM-WM neural networks in naPPA that support fluent, grammatical expression. These findings emphasize the role of large-scale neural networks in language, and demonstrate associated language deficits in naPPA. © 2012 Elsevier Inc.",,"Grossman, M.;Powers, J.;Ash, S.;McMillan, C.;Burkholder, L.;Irwin, D.;Trojanowski, J. Q.",2013,November,,0,
4119,Category-specific semantic memory: Converging evidence from bold fMRI and Alzheimer's disease,"Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. ""banana:lemon-COLOR""). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural kinds. The dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas. © 2012 Elsevier Inc.",aged;Alzheimer disease;article;association cortex;BOLD signal;brain atrophy;clinical article;controlled study;decision making;diffusion tensor imaging;female;functional magnetic resonance imaging;gray matter;human;male;nerve cell network;nerve projection;neuroimaging;occipital cortex;prefrontal cortex;priority journal;semantic memory;temporal cortex;tractography;white matter;Siemens Trio scanner,"Grossman, M.;Peelle, J. E.;Smith, E. E.;McMillan, C. T.;Cook, P.;Powers, J.;Dreyfuss, M.;Bonner, M. F.;Richmond, L.;Boller, A.;Camp, E.;Burkholder, L.",2013,,,0,
4120,Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis,"IMPORTANCE: An increasingly varied clinical spectrum of cases with amyotrophic lateral sclerosis (ALS) has been identified, and objective criteria for clinical trial eligibility are necessary. OBJECTIVE: To develop a cerebrospinal fluid (CSF) biomarker sensitive and specific for the diagnosis of ALS. DESIGN, SETTING, AND PARTICIPANTS: A case-control study including 51 individuals with ALS and 23 individuals with a disorder associated with a 4-repeat tauopathy was conducted at an academic medical center. MAIN OUTCOMES AND MEASURES: The CSF level of tau phosphorylated at threonine 181 (ptau) and ratio of ptau to total tau (ttau). RESULTS: Using a cross-validation prediction procedure, we found significantly reduced CSF levels of ptau and the ptau:ttau ratio in ALS relative to 4-repeat tauopathy and to controls. In the validation cohort, the receiver operating characteristic area under the curve for the ptau:ttau ratio was 0.916, and the comparison of ALS with 4-repeat tauopathy showed 92.0%sensitivity and 91.7%specificity. Correct classification based on a low CSF ptau:ttau ratio was confirmed in 18 of 21 cases (86%) with autopsy-proved or genetically determined disease. In patients with available measures, ptau:ttau in ALS correlated with clinical measures of disease severity, such as the Mini-Mental State Examination (n = 51) and ALS Functional Rating Scale-Revised (n = 42), and regression analyses related the ptau:ttau ratio to magnetic resonance imaging (n = 10) evidence of disease in the corticospinal tract and white matter projections involving the prefrontal cortex. CONCLUSIONS AND RELEVANCE: The CSF ptau:ttau ratio may be a candidate biomarker to provide objective support for the diagnosis of ALS. Copyright 2014 American Medical Association. All rights reserved.",,"Grossman, M.;Elman, L.;McCluskey, L.;McMillan, C. T.;Boller, A.;Powers, J.;Rascovsky, K.;Hu, W.;Shaw, L.;Irwin, D. J.;Lee, V. M. Y.;Trojanowski, J. Q.",2014,April,,0,
4121,Whole brain-based computerized neuroimaging in ALS and other motor neuron disorders,"Advanced neuroimaging applications to patients suffering from ALS and other motor neuron disorders (MND) have a high potential in terms of understanding the pathophysiology and visualizing the in vivo pathoanatomy of the diseases. In this context, particularly observer-independent computerized analyses of magnetic resonance imaging (MRI) data are of special interest since they overcome shortcomings of region-of-interest-based techniques. For three-dimensional structural T1-weighted MRI of the whole brain, voxel-based morphometry (VBM) has proven the most valuable approach to analyse regional volume alterations of the grey or white matter at group level. For the analysis of the white matter integrity with respect to tissue diffusivity and white matter connectivity including fibre tracking algorithms, diffusion tensor imaging (DTI) which can also be performed on a whole brain-basis is of the highest potential to date. Both VBM and DTI have been applied to various MND, in particular ALS, in multiple studies over recent years and have substantially broadened our knowledge about their in vivo pathoanatomy and mechanisms of neurodegeneration. Especially both the degree of damage to motor areas and the involvement of non-motor areas are of interest to be subjected to quantitative assessment, in order to establish quantitative surrogate markers for disease progression usable in clinical trials. Here, the technical state-of-the-art and the results of VBM and DTI studies in MND as the current state are reviewed, and future perspectives for further neuroimaging applications are highlighted.",,"Grosskreutz, J.;Peschel, T.;Unrath, A.;Dengler, R.;Ludolph, A. C.;Kassubek, J.",2008,2008,,0,
4122,Findings of psychopathology and computerized tomography in neuropsychiatric diseases,"1978-1980 we examined 451 patients of the Psychiatric University Clinic of Bonn by computerized tomography. From 260 patients with characterized diseases of the brain and brain damage, 78 patients had neutropsychiatric diseases of old age, i.e. cerebro-vascular processes (average age of 63.7 years) and 9 patients had primary degenerative processes of the brain (average age of 62.1 years). Patients with diseases of the cerebral vessels showed irreversible psychopathological syndromes in 87% (68 cases). The rate of pathological findings in CT increases in relation to degree of severity of the chronic (irreversible) organic psychosyndromes from 76% in pseudoneurasthenic syndromes to 93% in patients with organic changes of personality and to 100% in patients with dementia. The ambiguity of the conception of the multi-infarct-dementia is discussed. Only 19% (13 cases) of the sample with irreversible psychopathological changes showed localized neurological deficits and infarctions revealed by CT, but none of them more than one. In all patients with dementia a cortical atrophy was found. There is a significant positive correlation between cerebral atrophy in CT and irreversible organic psychosyndrome. These findings with computerized tomography demonstrate, in accordance with earlier pneumoencephalographic findings, that distinct types of irreversible psychosyndromes can be correlated to distinct types of cerebral atrophy. But these statistical correlations between the degree of the severity of the loss of psychic functions and the reduction of cerebral tissue are not necessarily valid for any single case.",age;brain dysfunction;central nervous system;computer analysis;computer assisted tomography;diagnosis;major clinical study;psychological aspect;psychosis;cerebrovascular accident,"Gross, G.;Huber, G.;Schuttler, R.",1982,,,0,
4123,"Location of cerebrovascular and degenerative changes, depressive symptoms and cognitive functioning in later life: the SMART-Medea study","OBJECTIVES: Depression and cognitive impairment are highly prevalent in later life and frequently co-occur. Structural changes in critical brain regions may underlie both conditions. The authors examined associations of infarcts, white-matter lesions (WML) and atrophy at different locations with depressive symptoms and cognitive functioning. METHODS: Within the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study, cross-sectional analyses were performed in 585 non-demented patients aged >/=50 years with symptomatic atherosclerotic disease. Volumetric measures of WML and atrophy were obtained with 1.5 T MRI; infarcts were rated visually. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (score >/=6). z Scores of executive functioning, memory and processing speed were calculated. Analyses were adjusted for age, sex, education, intelligence, vascular disease, physical functioning and co-occurring brain changes. RESULTS: Depressive symptoms were present in 102 (17%) patients and were associated with poorer memory (B=-0.26, 95% CI -0.47 to -0.06). Large subcortical infarcts and lacunar infarcts in deep white-matter tracts were both associated with depressive symptoms (RR=2.66, 95% CI 1.28 to 5.54; RR=2.02, 95% CI 1.14 to 3.59) and poorer executive functioning and memory. Periventricular WML volume was associated with poorer executive functioning; cortical infarcts in the left hemisphere and media flow region, ventricular volume and cortical atrophy were associated with a slower processing speed. CONCLUSION: In this sample of non-demented older persons, subcortical infarcts contributed to an increased risk of depressive symptoms as well as cognitive impairment. This depended on location in projecting white-matter tracts, and not on infarct size.","Age Factors;Aged;Amnesia/diagnosis/epidemiology/physiopathology;Atrophy;Brain/*pathology;Cerebral Infarction/*diagnosis/epidemiology/physiopathology;Cognition Disorders/*diagnosis/epidemiology/physiopathology;Cohort Studies;Cross-Sectional Studies;Depressive Disorder/*diagnosis/epidemiology/physiopathology;Dominance, Cerebral/physiology;Executive Function/physiology;Female;Humans;Incidence;Intracranial Arteriosclerosis/diagnosis/epidemiology/physiopathology;Leukoencephalopathies/*diagnosis/epidemiology/physiopathology;Magnetic Resonance Imaging;Male;Middle Aged;Netherlands;Neurodegenerative Diseases/*diagnosis/epidemiology/physiopathology;Neuropsychological Tests/statistics & numerical data;Psychometrics;Reaction Time/physiology;Statistics as Topic","Grool, A. M.;van der Graaf, Y.;Mali, W. P.;Geerlings, M. I.",2011,Oct,10.1136/jnnp.2010.232413,0,
4124,Structural MRI correlates of apathy symptoms in older persons without dementia: AGES-Reykjavik Study,"OBJECTIVE: We aimed to investigate the relation between apathy symptoms and structural brain changes on MRI, including white matter lesions (WMLs) and atrophy, in a large cohort of older persons. METHODS: Cross-sectional analyses are based on 4,354 persons without dementia (aged 76 +/- 5 years) participating in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study. Apathy symptoms were assessed with 3 items from the 15-item Geriatric Depression Scale. Brain volumes and total WML volume were estimated on 1.5-tesla MRI using an automated segmentation program; regional WML load was calculated using a semiquantitative scale. Regression analyses were adjusted for age, sex, education, intracranial volume, vascular risk factors, physical activity, brain infarcts, depressive symptoms, antidepressants, and cognitive status. RESULTS: Compared to those with <2 apathy symptoms, participants with >/= 2 apathy symptoms (49% of the cohort) had significantly smaller gray matter volumes (mean adjusted difference -3.6 mL, 95% confidence interval [CI] -6.2 to -1.0), particularly in the frontal and temporal lobes; smaller white matter volumes (mean adjusted difference -1.9 mL, 95% CI -3.6 to -0.3), mainly in the parietal lobe; and smaller thalamus volumes. They were also more likely to have WMLs in the frontal lobe (adjusted odds ratio = 1.08, 95% CI 0.9-1.3). Excluding participants with a depression diagnosis did not change the associations. CONCLUSIONS: In this older population without dementia, apathy symptoms are associated with a more diffuse loss of both gray and white matter volumes, independent of depression.","Aged;Aged, 80 and over;Aging/*pathology;*Apathy;Brain/*pathology;Cohort Studies;Cross-Sectional Studies;Depression/pathology;Female;*Geriatric Assessment;Humans;Magnetic Resonance Imaging;Male;Psychiatric Status Rating Scales","Grool, A. M.;Geerlings, M. I.;Sigurdsson, S.;Eiriksdottir, G.;Jonsson, P. V.;Garcia, M. E.;Siggeirsdottir, K.;Harris, T. B.;Sigmundsson, T.;Gudnason, V.;Launer, L. J.",2014,May 6,10.1212/wnl.0000000000000378,0,
4125,Improved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology,"The histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing. The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections. This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs. © 2009 Elsevier B.V. All rights reserved.",adult;aged;aging;article;autopsy;biotechnology;brain blood vessel;clinical article;clinical protocol;computer assisted diagnosis;diffusion tensor imaging;female;histopathology;human;male;neuropathology;nuclear magnetic resonance imaging;priority journal;qualitative diagnosis;quantitative diagnosis;three dimensional imaging;white matter,"Grinberg, L. T.;Amaro Junior, E.;da Silva, A. V.;da Silva, R. E.;Sato, J. R.;dos Santos, D. D.;de Paula Pacheco, S.;de Lucena Ferretti, R. E.;Paraizo Leite, R. E.;Pasqualucci, C. A.;Teipel, S. J.;Flatz, W. H.;Heinsen, H.",2009,,,0,
4126,White matter hyperintensities predict amyloid increase in Alzheimer's disease,"Impaired amyloid clearance probably contributes to increased amyloid deposition in sporadic Alzheimer's disease (AD). Diminished perivascular drainage due to cerebral small-vessel disease (CSVD) has been proposed as a cause of reduced amyloid clearance. White matter hyperintensities (WMHs) are considered to reflect CSVD and can be measured using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Amyloid deposition can be determined in vivo using Pittsburgh compound B ([11C]PiB) positron emission tomography (PET). We aimed to elucidate the association between WMH and the progression of amyloid deposition in patients with AD. Twenty-two patients with probable AD underwent FLAIR-MRI and [11C]PiB-PET examinations at baseline (BL) and after a mean follow-up (FU) interval of 28 months. The relationship between BL-WMH and the progression of cerebral amyloid between BL and FU was examined using a regions-of-interest (ROI) approach. The region-specific variability of this relationship was analyzed using a voxel-based method. The longitudinal analysis revealed a statistically significant association between the amount of BL-WMH and the progression of amyloid load between BL and FU (p = 0.006, adjusted R2 = 0.375, standardized coefficient beta = 0.384). The association was particularly observed in parieto-occipital regions and tended to be closer in regions adjacent to the brain surface. According to our knowledge, this is the first in vivo study in human being supporting the hypothesis that impaired amyloid clearance along perivascular drainage pathways may contribute to beta-amyloid deposition in sporadic AD. The extent of WMH might be a relevant factor to be assessed in antiamyloid drug trials.","Aged;Alzheimer Disease/genetics/ pathology/radionuclide imaging;Amyloid/ metabolism;Aniline Compounds;Apolipoprotein E4/genetics;Brain/ pathology/radionuclide imaging;Brain Mapping;Cross-Sectional Studies;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography;Predictive Value of Tests;Psychiatric Status Rating Scales;Thiazoles","Grimmer, T.;Faust, M.;Auer, F.;Alexopoulos, P.;Forstl, H.;Henriksen, G.;Perneczky, R.;Sorg, C.;Yousefi, B. H.;Drzezga, A.;Kurz, A.",2012,Dec,10.1016/j.neurobiolaging.2012.01.016,0,
4127,Computed tomography changes in patients with Parkinsonism,"Parkinsonism most frequently is due to Parkinson's disease (PD), but may be found in a number of different neurodegenerative diseases, Wilson's disease, Alzheimer's disease, Creutzfeldt-Jacob's disease, brain vascular disorders and multiinfarction encephalopathy, normal pressure hydrocephalus, posttraumatic encephalopathy, etc. When computed tomography (CT) is performed on patients with PD, it does not schow significant brain changes except brain atrophy, which in most cases is indistinguishable from brain involution, typical for aging. CT is mainly used to exclude other etiology of parkinsonian syndrome. The aim of this study is to analyse the computed tomography changes in patients diagnosed with parkinsonism. We have examined 170 patients with parkinsonism, aged between 27 and 83, 102 of whom were men and 68 women. All patients have been hospitalized and have had CT performed. Eighty patients (47%) were with normal for their age CT and 90 patients (53%) had CT abnormalities. Patients with abnormal CT were predominantly aged above 60 years (68 out of 90, or 75.5%) and they have had PD more than 5 years (53 out of 90, or 58.8%). The most common abnormality was cortical atrophy (78 out of 170 patients, or 45.9 %) - isolated in 45 patients (26.5%), combined with internal hydrocephalus in 12 patients (7%) and with ischemic lesions in 21 patients (12.3%). Ischemic lesions have been observed in 27 patients (15.9%), in 17 of them (10%) multiinfarction encephalopathy, large ischemia in 6 patients (3.5%), lacunar infarctions in 4 patients (2.3%). Three patients with ventriculomegaly have been diagnosed with normal pressure hydrocephalus. Two patients with CT data for cerebellar atrophy have been also suspected of having olivopontocerebellar atrophy. One female patient with cortical and cerebellar atrophy has been diagnosed with postencephalitic parkinsonism and one female patient with calcifications in the basal ganglia has been diagnosed with Fahr's disease. We have also found in two patients falx meningioma and falx osteoma, but we view this as an accident that does not follow a common trend. Our conclusion is that CT is necessary for the evaluation of the stage of the degenerative process in PD and for the discovery of concomitant diseases most common of which is multiinfarction dementia, which additionally worsen the neurological deficit.",adult;age;aged;article;basal ganglion;brain atrophy;brain calcification;brain disease;brain infarction;brain ischemia;brain ventricle dilatation;clinical examination;clinical feature;comorbidity;computer assisted tomography;controlled study;degenerative disease;disease course;disease duration;disease severity;Fahr disease;female;hospitalization;human;hydrocephalus;image analysis;major clinical study;male;medical assessment;meningioma;multiinfarct dementia;normotensive hydrocephalus;olivopontocerebellar atrophy;osteoma;Parkinson disease;parkinsonism;sex difference,"Grigorova, O.;Petrova, I.;Vaneva, S.;Sarafov, S.",2004,,,0,
4128,BIANCA (Brain Intensity AbNormality Classification Algorithm): A new tool for automated segmentation of white matter hyperintensities,"Reliable quantification of white matter hyperintensities of presumed vascular origin (WMHs) is increasingly needed, given the presence of these MRI findings in patients with several neurological and vascular disorders, as well as in elderly healthy subjects. We present BIANCA (Brain Intensity AbNormality Classification Algorithm), a fully automated, supervised method for WMH detection, based on the k-nearest neighbour (k-NN) algorithm. Relative to previous k-NN based segmentation methods, BIANCA offers different options for weighting the spatial information, local spatial intensity averaging, and different options for the choice of the number and location of the training points. BIANCA is multimodal and highly flexible so that the user can adapt the tool to their protocol and specific needs. We optimised and validated BIANCA on two datasets with different MRI protocols and patient populations (a “predominantly neurodegenerative” and a “predominantly vascular” cohort). BIANCA was first optimised on a subset of images for each dataset in terms of overlap and volumetric agreement with a manually segmented WMH mask. The correlation between the volumes extracted with BIANCA (using the optimised set of options), the volumes extracted from the manual masks and visual ratings showed that BIANCA is a valid alternative to manual segmentation. The optimised set of options was then applied to the whole cohorts and the resulting WMH volume estimates showed good correlations with visual ratings and with age. Finally, we performed a reproducibility test, to evaluate the robustness of BIANCA, and compared BIANCA performance against existing methods. Our findings suggest that BIANCA, which will be freely available as part of the FSL package, is a reliable method for automated WMH segmentation in large cross-sectional cohort studies.",adult;age;aged;algorithm;article;automated segmentation;automation;Brain Intensity AbNormality Classification Algorithm;controlled study;female;human;imaging and display;k nearest neighbor;major clinical study;male;multimodal imaging;neuroimaging;nuclear magnetic resonance imaging;priority journal;reproducibility;white matter lesion,"Griffanti, L.;Zamboni, G.;Khan, A.;Li, L.;Bonifacio, G.;Sundaresan, V.;Schulz, U. G.;Kuker, W.;Battaglini, M.;Rothwell, P. M.;Jenkinson, M.",2016,,,0,
4129,Effective artifact removal in resting state fMRI data improves detection of DMN functional connectivity alteration in Alzheimer's disease,"Artifact removal from resting state fMRI data is an essential step for a better identification of the resting state networks and the evaluation of their functional connectivity (FC), especially in pathological conditions. There is growing interest in the development of cleaning procedures, especially those not requiring external recordings (data-driven), which are able to remove multiple sources of artifacts. It is important that only inter-subject variability due to the artifacts is removed, preserving the between-subject variability of interest-crucial in clinical applications using clinical scanners to discriminate different pathologies and monitor their staging. In Alzheimer's disease (AD) patients, decreased FC is usually observed in the posterior cingulate cortex within the default mode network (DMN), and this is becoming a possible biomarker for AD. The aim of this study was to compare four different data-driven cleaning procedures (regression of motion parameters; regression of motion parameters, mean white matter and cerebrospinal fluid signal; FMRIB's ICA-based Xnoiseifier-FIX-cleanup with soft and aggressive options) on data acquired at 1.5 T. The approaches were compared using data from 20 elderly healthy subjects and 21 AD patients in a mild stage, in terms of their impact on within-group consistency in FC and ability to detect the typical FC alteration of the DMN in AD patients. Despite an increased within-group consistency across subjects after applying any of the cleaning approaches, only after cleaning with FIX the expected DMN FC alteration in AD was detectable. Our study validates the efficacy of artifact removal even in a relatively small clinical population, and supports the importance of cleaning fMRI data for sensitive detection of FC alterations in a clinical environment.",,"Griffanti, L.;Dipasquale, O.;Lagana, M. M.;Nemni, R.;Clerici, M.;Smith, S. M.;Baselli, G.;Baglio, F.",2015,,10.3389/fnhum.2015.00449,0,
4130,HIR naktivitaet-physical activity and healthy ageing-influence of small vessel disease,"BACKGROUND: Growing old in good physical and mental shape is of great personal and economical interest for both the individual and the society. Known predictors of healthy ageing are high physical, intellectual and spiritual activity during lifetime, high socioeconomic status and mediterranean diet. In our project HIRNaktivitaet we are investigating the effect of the initiation of a regular physical work-out on memory functions in a cohort of non-demented senior citizens. In addition, we will analyse the impact of incidental small vessel lesions on the adaptive mechanisms. METHODS: HIRNaktivitaet is a randomised, single-centre, partial cross-over clinical trial. Out of 128 candidates aged >60 years, 71 were randomised in five groups. Structured physical training, comprising of three one-hour units of aerobic exercise per week in a period of three months, is being conducted in a collaborating fitness centre. Preceding a three-month control phase and before and after the training cycle the following investigations are being performed: neurological examination and history, assessment of adverse events, stance and gait testing ( including a computerised gait analysis), ECG, lab tests (vascular risk profile, cardiac enzymes), spiroergometry, body impedance analysis, neuropsychological testing (with emphasis on working memory and executive functions) and an MRI scan (fMRI with working memory paradigm, connectivity analysis, DTI, MP-RAGE, 3D-FLAIR, SWI). RESULTS: The study is ongoing, two of the five groups have finished the three-month training cycle. 22 of these 26 participants were very satisfied with the experience and continue with the training. The other three groups will be practising until May 2012. CONCLUSIONS: HIRNaktivitaet addresses several important scientific questions concerning healthy aging and its underlying mechanisms. In particular, neuronal plasticity will be analysed on white and grey matter levels. Preliminary results of the study will be communicated.",aging;cerebrovascular accident;physical activity;human;gait;working memory;manual labor;Mediterranean diet;society;impedance;crossover procedure;training;aerobic exercise;aged;social status;memory;neurologic examination;risk;lifespan;fitness;nerve cell plasticity;executive function;functional magnetic resonance imaging;gray matter;standing;nuclear magnetic resonance imaging;electrocardiogram;enzyme,"Griebe, M.;Bahr, C.;Schafer, A.;Leweling, H.;Saur, J.;Eisele, P.;Blahak, C.;Gass, A.;Hennerici, M. G.;Szabo, K.",2012,,10.1159/000339538,0,
4131,"A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23","Childhood ataxias are a complex set of inherited disorders. Ataxias associated with generalized tonic-clonic epilepsy are usually included with the progressive myoclonus epilepsies (PME). Five disease entities, Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinoses, myoclonic epilepsy with ragged red fibres and sialidoses, account for the majority of PME cases. Two rare forms of ataxia plus epilepsy, sensory ataxic neuropathy, dysarthria and ophthalmoparesis, and infantile onset spinocerebellar ataxia were described recently and found to be caused by defective mitochondrial proteins. We report here a large consanguineous family from Saudi Arabia with four affected children presenting with generalized tonic-clonic epilepsy, ataxia and mental retardation, but neither myoclonus nor mental deterioration. MRI and muscle biopsy of one patient revealed, respectively, posterior white matter hyperintensities and vacuolization of the sarcotubular system. We localized the defective gene by homozygosity mapping to a 19 Mb interval in 16q21-q23 between markers D16S3091 and D16S3050. Linkage studies in this region will allow testing for homogeneity of this novel ataxia-epilepsy entity. © The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.",adolescent;adult;article;ataxia;autosomal recessive disorder;case report;female;gene location;gene mapping;genetic linkage;grand mal epilepsy;homozygosity;human;male;mental deficiency;muscle biopsy;myoclonus epilepsy;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;priority journal;sarcoplasmic reticulum;Saudi Arabia;school child;white matter,"Gribaa, M.;Salih, M.;Anheim, M.;Lagier-Tourenne, C.;H'Mida, D.;Drouot, N.;Mohamed, A.;Elmalik, S.;Kabiraj, M.;Al-Rayess, M.;Almubarak, M.;Bétard, C.;Goebel, H.;Koenig, M.",2007,,,0,
4132,Neuropsychiatry and White Matter Microstructure in Huntington's Disease,"Background: Neuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population. Objective:We used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD. Methods: DTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics.We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO). Results: For those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain. Conclusions:We demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.",,"Gregory, S.;Scahill, R. I.;Seunarine, K. K.;Stopford, C.;Zhang, H.;Zhang, J.;Orth, M.;Durr, A.;Roos, R. A. C.;Langbehn, D. R.;Long, J. D.;Johnson, H.;Rees, G.;Tabrizi, S. J.;Craufurd, D.;Campbell, C.;Campbell, M.;Labuschagne, I.;Milchman, C.;Coleman, A.;Dar Santos, R.;Decolongon, J.;Sturrock, A.;Jauffret, C.;Justo, D.;Lehericy, S.;Marelli, C.;Nigaud, K.;Valabrègue, R.;Bechtel, N.;Bohlen, S.;Van Den Bogaard, S. J. A.;Dumas, E. M.;Van Der Grond, J.;E.P, T. H.;Arran, N.;Callaghan, J.;Cash, D. M.;Crawford, H.;Fox, N. C.;Hobbs, N. Z.;Lahiri, N.;Malone, I.;Read, J.;Say, M. J.;Whitehead, D.;Wild, E.;Jones, R.;Axelson, E.;Queller, S.",2015,29,,0,
4133,Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington's Disease,"Background: Huntington's disease is marked by progressive neuroanatomical changes, assumed to underlie the development of the disease's characteristic symptoms. Previous work has demonstrated longitudinal macrostructural white-matter atrophy, with some evidence of microstructural change focused in the corpus callosum. Objective: To more accurately characterise longitudinal patterns, we examined white matter microstructural change using Diffusion Tensor Imaging (DTI) data from three timepoints over a 15 month period. Methods: In 48 early-stage HD patients and 36 controls from the multi-site PADDINGTON project, diffusion tensor imaging (DTI) was employed to measure changes in fractional anisotropy (FA) and axial (AD) and radial diffusivity (RD) in 24 white matter regions-of-interest (ROIs). Results: Cross-sectional analysis indicated widespread baseline between-group differences, with significantly decreased FA and increased AD and RD found in HD patients across multiple ROIs. Longitudinal rates of change differed significantly between HD patients and controls in the genu and body of corpus callosum, corona radiata and anterior limb of internal capsule. Change in RD in the body of the corpus callosum was significantly associated with baseline disease burden, but other clinical associations were not significant. Conclusions:We detected subtle longitudinal white matter changes in early HD patients. Progressive white matter abnormalities in HD may not be uniform throughout the brain, with some areas remaining static in the early symptomatic phase. Longer assessment periods across disease stages will help map this progressive trajectory.",,"Gregory, S.;Cole, J. H.;Farmer, R. E.;Rees, E. M.;Roos, R. A. C.;Sprengelmeyer, R.;Durr, A.;Landwehrmeyer, B.;Zhang, H.;Scahill, R. I.;Tabrizi, S. J.;Frost, C.;Hobbs, N. Z.",2015,27,,0,
4134,Incidental Cerebral Microbleeds and Cerebral Blood Flow in Elderly Individuals,"IMPORTANCE: Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE: To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, beta-amyloid (Abeta), and cognition. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS: 3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Abeta. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES: Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Abeta were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS: The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P = .60). CONCLUSIONS AND RELEVANCE: In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.","Aged;Aged, 80 and over;Aging/ pathology;Apolipoproteins E/genetics;Cerebral Amyloid Angiopathy/epidemiology/pathology;Cerebral Hemorrhage/ epidemiology/genetics/ pathology;Cerebrovascular Circulation/ physiology;Cross-Sectional Studies;Female;Humans;Imaging, Three-Dimensional;Incidence;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Positron-Emission Tomography","Gregg, N. M.;Kim, A. E.;Gurol, M. E.;Lopez, O. L.;Aizenstein, H. J.;Price, J. C.;Mathis, C. A.;James, J. A.;Snitz, B. E.;Cohen, A. D.;Kamboh, M. I.;Minhas, D.;Weissfeld, L. A.;Tamburo, E. L.;Klunk, W. E.",2015,Sep,10.1001/jamaneurol.2015.1359,0,
4135,Venous hypertension associated with a posterior fossa dural arteriovenous fistula: Another cause of bithalamic lesions on MR images,"We report a case of a posterior fossa arteriovenous fistula (AVF) with bithalamic hyperintensity on MR images. The thalamic abnormality improved after surgery, suggesting reversible venous hypertension as the pathogenesis of the finding, as opposed to infarction. This manifestation of a posterior fossa AVF should be considered in the differential diagnosis of bilateral thalamic disease.",,"Greenough, G. P.;Mamourian, A.;Harbaugh, R. E.",1999,1999,,0,
4136,Alzheimer disease and nonfluent progressive aphasia,"Objective: To describe a patient with pathologically proven Alzheimer disease (AD) who presented with a nonfluent progressive aphasic syndrome. Designs: Longitudinal neuropsychological assessment, structural (magnetic resonance imaging) and functional (single photon emission computed tomography) imaging, and postmortem brain examination. Setting: Memory and cognitive disorders clinic in a tertiary referral hospital. Patient: A 66- year-old man presented with a 5-year history of progressive nonfluent aphasia characterized by marked deficits in phonology and syntax with preservation of everyday abilities. His condition deteriorated rapidly and he died suddenly of a myocardial infarction 12 months later. Results: Neuropsychological testing revealed mild global intellectual impairment with marked impairment of auditory verbal short-term memory, syntactic, and phonological abilities. His naming errors were predominantly phonological paraphasias. Magnetic resonance imaging scans showed left perisylvian atrophy and results of a Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomographic scan were normal. Postmortem pathological examination revealed typical AD pathological features with atypical distribution, involving predominantly perisylvian language areas, but sparing the medial temporal lobe. Conclusions: The language deficits in AD, which have received considerable attention, are thought to involve predominantly lexicosemantic processes. When AD presents as a relatively isolated language disturbance, the aphasia is usually of the fluent anomic type. To our knowledge, our patient represents the first fully documented case of progressive nonfluent aphasia with pathologically verified AD.",,"Greene, J. D. W.;Patterson, K.;Xuereb, J.;Hodges, J. R.",1996,October,,0,
4137,The clinical spectrum of cerebral amyloid angiopathy: Presentations without lobar hemorrhage,"Cerebral amyloid angiopathy is a common cause of spontaneous lobar hemorrhage in elderly patients. We discuss seven patients with amyloid angiopathy presenting without major lobar hemorrhage. The patients' presentations fell into two groups: recurrent transient neurologic symptoms and rapidly progressive dementia. The cases with transient episodes had a spread of symptoms to contiguous body areas during episodes. Each had evidence of small hemorrhage or subsequent large hemorrhage in the cortical location corresponding to the symptoms, suggesting petechial hemorrhage with focal seizure as the cause of the transient spells. Three cases of dementia developed with relatively rapid time courses, progressing from intact baseline to profound dementia in spans of a few days to 2 years. Pathologic abnormalities, in addition to amyloid angiopathy, included patchy white matter demyelination and tissue loss, petechial cortical hemorrhages, cortical infarctions, and a variable degree of neuritic plaques and neurofibrillary tangles. The clinical spectrum of cerebral amyloid angiopathy includes these two neurologic syndromes.",amyloid;congo red;thioflavine;adult;aged;article;autopsy;brain biopsy;brain hemorrhage;clinical article;clinical feature;computer assisted tomography;dementia;electroencephalogram;female;human;immunocytochemistry;immunohistochemistry;male;microscopy;neurologic examination;nuclear magnetic resonance imaging;priority journal;vascular amyloidosis,"Greenberg, S. M.;Vonsattel, J. P. G.;Stakes, J. W.;Gruber, M.;Finklestein, S. P.",1993,,,0,
4138,Case 22-2010: An 87-year-old woman with dementia and a seizure,"An 87-year-old woman with a history of dementia was admitted to this hospital because of a seizure. A diagnosis of possible Alzheimer's disease had been made 4 years earlier; at baseline, she recognized only her husband and children. On examination, she was unresponsive. Magnetic resonance imaging scans of the brain revealed T(2)-weighted hyperintensities in the white matter involving both cerebral hemispheres, as well as innumerable small foci of susceptibility-weighted artifact at the cortical-subcortical junction. Despite a temporary improvement after treatment, she died of pneumonia a few days later. An autopsy was performed. Copyright © 2010 Massachusetts Medical Society. All rights reserved.",,"Greenberg, S. M.;Rapalino, O.;Frosch, M. P.",2010,22,,0,
4139,Detection of isolated cerebrovascular β-amyloid with Pittsburgh compound B,"Imaging of cerebrovascular β-amyloid (cerebral amyloid angiopathy) is complicated by the nearly universal overlap of this pathology with Alzheimer's pathology. We performed positron emission tomographic imaging with Pittsburgh Compound B on 42-year-old man with early manifestations of Iowa-type hereditary cerebral amyloid angiopathy, a form of the disorder with little or no plaque deposits of fibrillar β-amyloid. The results demonstrated increased Pittsburgh Compound B retention selectively in occipital cortex, sparing regions typically labeled in Alzheimer's disease. These results offer compelling evidence that Pittsburgh Compound B positron emission tomography can noninvasively detect isolated cerebral amyloid angiopathy before overt signs of tissue damage such as hemorrhage or white matter lesions.",,"Greenberg, S. M.;Grabowski, T.;Gurol, M. E.;Skehan, M. E.;Nandigam, R. N. K.;Becker, J. A.;Garcia-Alloza, M.;Prada, C.;Frosch, M. P.;Rosand, J.;Viswanathan, A.;Smith, E. E.;Johnson, K. A.",2008,November,,0,
4140,Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS),"Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects carriers, principally males, of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Clinical features of FXTAS include progressive intention tremor and gait ataxia, accompanied by characteristic white matter abnormalities on MRI. The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neurons and astrocytes throughout the CNS. Prior to the current work, the nature of the associations between inclusion loads and molecular measures (e.g. CGG repeat) was not defined. Post-mortem brain and spinal cord tissue has been examined for gross and microscopic pathology in a series of 11 FXTAS cases (males, age 67-87 years at the time of death). Quantitative counts of inclusion numbers were performed in various brain regions in both neurons and astrocytes. Inclusion counts were compared with specific molecular (CGG repeat, FMR1 mRNA level) and clinical (age of onset, age of death) parameters. In the current series, the three most prominent neuropathological characteristics are (i) significant cerebral and cerebellar white matter disease, (ii) associated astrocytic pathology with dramatically enlarged inclusion-bearing astrocytes prominent in cerebral white matter and (iii) the presence of intranuclear inclusions in both brain and spinal cord. The pattern of white matter pathology is distinct from that associated with hypertensive vascular disease and other diseases of white matter. Spongiosis was present in the middle cerebellar peduncles in seven of the eight cases in which those tissues were available for study. There is inclusion formation in cranial nerve nucleus XII and in autonomic neurons of the spinal cord. The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions). © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.",fragile X mental retardation protein;messenger RNA;aged;allele;article;astrocyte;autonomic nerve;autopsy;brain atrophy;brain region;brain spongiosis;brain tissue;cell count;cell nucleus inclusion body;clinical article;clinical feature;clinical trial;controlled clinical trial;controlled study;death;degenerative disease;disease association;disease course;fragile x associated tremor ataxia syndrome;fragile X syndrome;functional magnetic resonance imaging;gene mutation;heterozygote;human;human tissue;hypertension;hypoglossal nerve;male;microscopy;neuropathology;nuclear magnetic resonance imaging;onset age;prediction;priority journal;quantitative analysis;spinal cord;white matter,"Greco, C. M.;Berman, R. F.;Martin, R. M.;Tassone, F.;Schwartz, P. H.;Chang, A.;Trapp, B. D.;Iwahashi, C.;Brunberg, J.;Grigsby, J.;Hessl, D.;Becker, E. J.;Papazian, J.;Leehey, M. A.;Hagerman, R. J.;Hagerman, P. J.",2006,,,0,
4141,Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease,"A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space. displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, Clq and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated β/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in non-familial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.",collagen;elastin;adult;Alzheimer disease;arteriole;artery disease;article;autosomal dominant disorder;basal ganglion;brain cortex atrophy;case report;computer assisted tomography;dementia;demyelination;familial disease;fibromuscular dysplasia;gliosis;human;immunofluorescence test;leukoencephalopathy;male;neurofibrillary tangle;priority journal;seizure;senile plaque;white matter,"Gray, F.;Robert, F.;Labrecque, R.;Chretient, F.;Baudrimont, M.;Fallet-Bianco, C.;Mikol, J.;Vinters, H. V.",1994,,,0,
4142,Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"To test the hypothesis that an apoptotic process plays a role in the pathogenesis of cerebral lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we examined samples from frontal, temporal, insular, and occipital regions, basal ganglia, and cerebellum from 4 patients with CADASIL, 2 with Binswanger disease, and 3 controls. Apoptotic cells were identified using in situ end labeling and activated caspase 3 immunostaining. Immunolabeling for Notch3, the beta-amyloid protein precursor, and phosphorylated neurofilament protein was performed on successive sections. Apoptosis of vascular cells was markedly increased in status cribrosus in CADASIL, both in basal ganglia and subcortical white matter, suggesting that concomitantly with Notch3 deposition it may play a causative role in the dilatation of Virchow-Robin spaces. Neuronal apoptosis was found in CADASIL, mostly in cortical layers 3 and 5. Its severity correlated semiquantitatively with the extent of ischemic lesions and axonal damage in the underlying white matter. It was more severe in demented patients. Only occasional apoptotic neurons were found in the Binswanger cases and none in the controls. This supports the view that neuronal apoptosis may contribute to cortical atrophy and cognitive impairment in patients with CADASIL and that it may, at least partly, result from axonal damage in the underlying white matter.","Adult;Aged;Aged, 80 and over;*Apoptosis;CADASIL/*pathology/*physiopathology;Caspase 3/metabolism;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Gray, F.;Polivka, M.;Viswanathan, A.;Baudrimont, M.;Bousser, M. G.;Chabriat, H.",2007,Jul,10.1097/nen.0b013e318093e574,0,
4143,Quantitative magnetic resonance abnormalities in creutzfeldt-jakob disease and fatal insomnia,"Background: Quantitative neuroimaging might unveil abnormalities in prion diseases that are not perceivable at visual inspection. On the other hand, scarce studies have quantified volumetric changes in prion diseases. Objectives: We aim to characterize volumetric and diffusion tensor imaging (DTI) changes in patients with prion diseases who presented with either Creutzfeldt-Jakob disease (CJD) or fatal insomnia (FI) phenotype. Methods: Twenty patients with prion diseases- 15 with CJD and 5 with fatal insomnia (FI)- and 40 healthy controls were examined with a 3-Tesla magnetic resonance imaging scanner. Images were segmented and normalized with SPM12. DTI maps were obtained with FMRIB Software Library. Whole-brain voxel-wise and region-of-interest analyses of volumetric and DTI changes were performed with SPM12. White matter (WM) changes were also analyzed with tract-based spatial statistics. Semiquantitive assessment of neuropathological parameters was compared with DTI metrics in thalamus from 11 patients. Results: Patients with CJD and FI presented significant atrophy in thalamus and cerebellum. In CJD, mean diffusivity (MD) was decreased in striatum and increased in subcortical WM, while both increased and decreased values were observed across different thalamic nuclei. In FI, MD was increased in thalamus and cerebellum. Spongiform change and PrPSc deposition were more intense in thalamus in CJD than in FI, although no significant correlations arose with MD values in the nuclei studied. Conclusion: Volumetric and DTI abnormalities suggest a central common role of the thalamus in prion diseases. We report, for the first time, quantitative MRI changes in FI, and provide further evidence of WM involvement in prion diseases.",adult;article;brain atrophy;cerebellum;clinical article;controlled study;corpus striatum;Creutzfeldt Jakob disease;diffusion tensor imaging;fatal familial insomnia;female;fusiform gyrus;human;human tissue;imaging software;lingual gyrus;male;medulla oblongata;middle aged;neuropathology;nuclear magnetic resonance scanner;phenotype;postcentral gyrus;primary motor cortex;prion disease;priority journal;quantitative analysis;thalamus;thalamus nucleus;white matter;Magnetom Trio Tim,"Grau-Rivera, O.;Calvo, A.;Bargalló, N.;Monté, G. C.;Nos, C.;Lladó, A.;Molinuevo, J. L.;Gelpi, E.;Sánchez-Valle, R.",2016,,10.3233/jad-160750,0,
4144,Mild cognitive impairment after lacunar infarction: voxel-based morphometry and neuropsychological assessment,"BACKGROUND: The aim of the present study was to investigate whether there were differences in neuroradiological features, including white-matter lesions and gray-matter volumes, between patients with lacunar infarction with and without mild cognitive impairment of the vascular type (MCI-V). METHODS: A total of 40 patients with lacunar infarction were studied within 1 month after stroke. RESULTS: MCI-V was found in 22 patients, who in comparison with patients without cognitive impairment were significantly older and had fewer years of formal education. MRI subcortical hyperintensities especially in the basal ganglia (putamen and thalamus) were significantly more frequent in the MCI-V group. In the voxel-based morphometric study, patients with MCI-V showed more atrophy bilaterally in the middle temporal gyrus, right and left frontal and posterior bilateral occipitoparietal regions including the posterior cingulate as well as in the cerebellum. A region of interest analysis restricted to the parahippocampi and hippocampi showed further reduced bilateral parahippocampal gyrus and right hippocampus volume reductions in this group of patients. Finally, the amount of white-matter lesions among MCI-V showed negative correlations with gray-matter volume in frontal and temporal areas as well as with the thalamus and mesencephalon. CONCLUSIONS: The present findings provide support for an anatomical substrate of the MCI entity in patients with lacunar infarction. Both gray- and white-matter changes seem to contribute to the cognitive impairment of such patients.","Aged;Aged, 80 and over;Atrophy;Basal Ganglia/pathology;Brain Infarction/*complications/pathology/psychology;Brain Mapping/*methods;Cerebellum/pathology;Cerebral Cortex/pathology;Cognition Disorders/*etiology/pathology/psychology;Dementia, Vascular/complications/*etiology/pathology/psychology;Female;Hippocampus/pathology;Humans;Image Interpretation, Computer-Assisted;*Magnetic Resonance Imaging;Male;Mesencephalon/pathology;*Neuropsychological Tests;Severity of Illness Index;Thalamus/pathology","Grau-Olivares, M.;Bartres-Faz, D.;Arboix, A.;Soliva, J. C.;Rovira, M.;Targa, C.;Junque, C.",2007,,10.1159/000099134,0,
4145,Neuropsychological dysfunction associated to lacuna r stroke,"Introduction: A number of investigations have been developed to date, to study the causes and risk factors leading to lacunar infarcts. However only few works were addressed to investigate the neuropsychological correlates of these cerebrovascular lesions. Objective: To correlate lacunar infarct topography with distinct patterns of cognitive dysfunction relating clinic aspects with magnetic resonance parameters and neuropsychological assessment. Methods: Twenty consecutive patients from the Neurology Service at the Sagrat Cor Hospital in Barcelona were included in the study. Al patients were diagnosed as presenting a lacunar syndrome according to Miller's and Fisher's classification: pure motor hemiparesis, pure sensitive syndrome, ataxia-hemiparesia, disartria-clumsy hand and sensitive-motor syndrome. Structural magnetic resonance images were acquired from all cases using T1 weighted, FLAIR and proton density (PD) sequences to distinguish between acute and chronic lacunar infarcts. Finally, all patients were assessed by means of an exhaustive neuropsychological battery. Results and conclusions: The following results were obtained: a) any syndrome group is characterized by presenting increased or reduced severity of lacunar infarcts, b) similarly, clinical groups did not differ in the amount of white matter damage as reflected by the presence of leuko-araiosis. C) Significant differences were found on the Benton's Line Orientation Test where patients with a disartria-clumsy hand syndrome exhibited better performance as compared to patients with pure sensitive syndrome. D) Significant differences were found in category and phonetic fluency tests between patients presenting with a single lacunar infarct and multiple infarct patients. E) Leuko-araiosis was not related to cognitive performance among patients. Present results indicate that lacunar infarcts, classically considered as 'silent' from a neurological perspective, may associate with significant neuropsychological dysfunction. Future studies should investigate whether patients exhibiting cognitive impairment caused by lacunar infarcts are at increased risk for developing dementia, particularly of a subcortical vascular type.",,"Grau-Olivares, M.;Arboix, A.;Bartrés-Faz, D.;Junqué, C.",2004,2004,,0,
4146,Higher severity of frontal periventricular white matter and basal ganglia hyperintensities in first-ever lacunar stroke with multiple silent lacunes,"BACKGROUND AND PURPOSE: We investigated whether patients with a lacunar infarct (LI) syndrome exhibiting unique LI or multiple LI on magnetic resonance imaging (MRI) examinations differed in terms of topography and severity of white matter hyperintensities (WMH) ratings. METHODS: Forty consecutive patients with a first-ever acute LI, who presented a lacunar syndrome according to Miller-Fisher's classification were recruited and were classified into a group presenting isolated LI on MRI (n = 17) or multiple LI (n = 23). RESULTS: Despite equivalent demographic, clinical and cognitive characteristics, patients with multiple LI had increased ratings of WMH in frontal, occipital and subcortical regions. No significant correlations could be evidenced between the number of LI and WMH ratings. CONCLUSIONS: Present findings provide support to previous hypothesis considering single and multiple LI MRI presentations of lacunar infarct patients as distinct entities.","Aged;Basal Ganglia/ pathology;Brain Infarction/ pathology/psychology;Dementia, Multi-Infarct/pathology;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Myelin Sheath/ pathology;Recurrence","Grau-Olivares, M.;Arboix, A.;Bartres-Faz, D.;Junque, C.",2008,Sep,10.1111/j.1468-1331.2008.02220.x,0,
4147,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy resulting in stroke in an 11-year-old male,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the Notch3 gene on chromosome 19. The condition manifests itself clinically typically in the third to fifth decade with migraine and recurrent episodes of stroke or transient ischaemic attacks. We report the case of an 11-year-old male with CADASIL resulting in stroke with right hemiparesis and dysphasia. Acute magnetic resonance imaging suggested infarction in the left hemisphere; magnetic resonance angiography revealed calibre variation of the intracerebral arteries. The patient suffered from common migraine with five to six attacks per month for 3 years 6 months before the stroke. Attacks occurred early in the morning with severe one-sided headache, photophobia, nausea, and vomiting. Antimigraine medications had no effect. The family history revealed more cases of CADASIL, with an autosomal dominant pattern. The diagnosis of CADASIL was confirmed by the finding of the known mutation of the Notch3 gene running in the family. With treatment in a neurorehabilitation centre the patient recovered most of his functions with only discrete fine-motor and cognitive sequelae. Our case report highlights the need for paediatricians to consider CADASIL in childhood stroke as well as in migraine patients. Copyright © 2009 Mac Keith Press.",,"Granild-Jensen, J.;Jensen, U. B.;Schwartz, M.;Hansen, U. S.",2009,2009,,0,
4148,Early alterations in functional connectivity and white matter structure in a transgenic mouse model of cerebral amyloidosis,"Impairment of brain functional connectivity (FC) is thought to be an early event occurring in diseases with cerebral amyloidosis, such as Alzheimer's disease. Regions sustaining altered functional networks have been shown to colocalize with regions marked with amyloid plaques burden suggesting a strong link between FC and amyloidosis. Whether the decline in FC precedes amyloid plaque deposition or is a consequence thereof is currently unknown. The sequence of events during early stages of the disease is difficult to capture in humans due to the difficulties in providing an early diagnosis and also in view of the heterogeneity among patients. Transgenic mouse lines overexpressing amyloid precursor proteins develop cerebral amyloidosis and constitute an attractive model system for studying the relationship between plaque and functional changes. In this study, ArcAbeta transgenic and wild-type mice were imaged using resting-state fMRI methods across their life-span in a cross-sectional design to analyze changes in FC in relation to the pathology. Transgenic mice show compromised development of FC during the first months of postnatal life compared with wild-type animals, resulting in functional impairments that affect in particular the sensory-motor cortex already in preplaque stage. These functional alterations were accompanied by structural changes as reflected by reduced fractional anisotropy values, as derived from diffusion tensor imaging. Our results suggest cerebral amyloidosis in mice is preceded by impairment of neuronal networks and white matter structures. FC analysis in mice is an attractive tool for studying the implications of impaired neuronal networks in models of cerebral amyloid pathology.","Aging/physiology;Alzheimer Disease/pathology;Amyloidosis/genetics/ pathology;Animals;Anisotropy;Female;Genotype;Humans;Male;Mice;Mice, Transgenic;Nerve Net/pathology;Neural Pathways/ physiology;White Matter/ anatomy & histology/growth & development","Grandjean, J.;Schroeter, A.;He, P.;Tanadini, M.;Keist, R.;Krstic, D.;Konietzko, U.;Klohs, J.;Nitsch, R. M.;Rudin, M.",2014,Oct 8,10.1523/jneurosci.4762-13.2014,0,
4149,White matter diffusivity predicts memory in patients with subjective and mild cognitive impairment and normal CSF total tau levels,"Subjective and mild cognitive impairment (SCI and MCI) are etiologically heterogeneous conditions. This poses problems for assessment of pathophysiological mechanisms and risk of conversion to dementia. Neuropsychological, imaging, and cerebrospinal fluid (CSF) findings serve to distinguish Alzheimers disease (AD) and other etiological subgroups. Tau-molecules stabilize axonal microtubuli; high CSF total tau (T-tau) reflects ongoing axonal damage consistent with AD. Here, we stratify patients by CSF T-tau pathology to determine if memory network diffusion tensor imaging (DTI) predicts memory performance in the absence of elevated T-tau. We analyzed neuropsychological test results, hippocampus volume (HcV) and white matter diffusivity in 45 patients (35 with normal T-tau). The T-tau pathology group showed more hippocampus atrophy and memory impairment than the normal T-tau group. In the T-tau normal group: (1) memory was related with white matter diffusivity [fractional anisotropy (FA) and radial diffusivity (DR)], and (2) FA of the genu corpus callosum was a unique predictor of variance for verbal learning, and HcV did not contribute to this prediction. The smaller sample size in the T-tau pathology group precludes firm conclusions. In the normal T-tau group, white matter tract and memory changes may be associated with normal aging, or with non-tau related pathological mechanisms. (JINS, 2010, 16, 5869.) © The International Neuropsychological Society 2009.",,"Grambaite, R.;Stenset, V.;Reinvang, I.;Walhovd, K. B.;Fjell, A. M.;Fladby, T.",2010,January,,0,
4150,Executive dysfunction in mild cognitive impairment is associated with changes in frontal and cingulate white matter tracts,"Mild cognitive impairment (MCI) may affect multiple neuropsychological domains. While amnestic MCI is associated with Alzheimer's disease, patterns of brain pathology in non-amnestic subtypes have been less studied. Twenty-three patients with attention/executive MCI (a/e MCI), seen at a university-based memory clinic, and 23 normal controls, matched according to age, gender, and education, were included in this study. All subjects were assessed with a neuropsychological test battery, including tests of memory, attention and executive function, and underwent magnetic resonance imaging. Diffusion tensor imaging derived white matter (WM) tract radial and mean diffusivity (DR and MD) were assessed using Tract-Based Spatial Statistics, and cortical thickness (CTH) was assessed using FreeSurfer. This study investigated changes of WM DR/MD and CTH in subjects with a/e MCI, and associations between these changes and different a/e subfunctions. WM DR/MD underlying rostral middle frontal, medial orbitofrontal, caudal anterior cingulate, posterior cingulate, retrosplenial and entorhinal cortices was higher for the a/e MCI than the control group, but CTH was not different from controls in any of the regions. WM DR/MD underlying superior frontal, rostral middle frontal, lateral/medial orbitofrontal and retrosplenial cortices were significantly associated with inhibition/switching performance, while caudal middle frontal CTH was significantly associated with attention and divided attention in the patient group. We conclude that increased WM DR/MD in frontal and cingulate regions and cortical thinning in caudal middle frontal region are both associated with executive dysfunction in MCI.","Aged;Case-Control Studies;Executive Function;Female;Frontal Lobe/ pathology;Gyrus Cinguli/ pathology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mild Cognitive Impairment/ pathology/psychology;Nerve Fibers, Myelinated/ pathology","Grambaite, R.;Selnes, P.;Reinvang, I.;Aarsland, D.;Hessen, E.;Gjerstad, L.;Fladby, T.",2011,,10.3233/jad-2011-110290,0,
4151,Pre-dementia memory impairment is associated with white matter tract affection,"Mild cognitive impairment (MCI), especially amnestic, often represents pre-dementia Alzheimer's disease, characterized by medial temporal lobe atrophy, while white matter (WM) alterations are insufficiently described. We analyze both cortical morphometric and WM diffusivity differences in amnestic versus non-amnestic subtypes and ask if memory and WM tract affection are related independently of cortical atrophy. Forty-nine patients from a university-hospital based memory clinic with a score of 3 on the Global Deterioration Scale aged 43-77 years (45% female) were included. Two neuropsychologists have classified cases as amnestic (aMCI), non-amnestic (naMCI), or less advanced (laMCI), not satisfying criteria for aMCI/naMCI. Diffusion tensor imaging (DTI) WM tract and morphometric data of the temporal-parietal memory network were compared among patient subtypes and related to story, word list, and visual memory. WM radial and mean diffusivity (DR and MD), underlying the entorhinal cortex, were higher in aMCI compared with laMCI. WM DR and MD, underlying the entorhinal, parahippocampal, and middle temporal cortex, explained unique variance in word list and story memory, and this was not due to secondary effects of cortical thinning. DTI may thus potentially aid diagnosis in early disease stages. ).","Adult;Aged;Brain/ pathology;Brain Mapping;Chi-Square Distribution;Diffusion Tensor Imaging/methods;Female;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Memory Disorders/classification/ pathology;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Regression Analysis","Grambaite, R.;Reinvang, I.;Selnes, P.;Fjell, A. M.;Walhovd, K. B.;Stenset, V.;Fladby, T.",2011,Jan,10.1017/s1355617710001360,0,
4152,Distinctive cognitive profiles in Alzheimer's disease and subcortical vascular dementia,"BACKGROUND: There are inconsistencies in published reports regarding the profile of cognitive impairments in vascular dementia, and its differentiation from Alzheimer's disease. OBJECTIVES: To identify the overall profile of cognitive impairment in subcortical vascular dementia as compared with Alzheimer's disease; and the tests which best discriminate between these groups. METHODS: 57 subjects participated: 19 with subcortical vascular dementia, 19 with Alzheimer's disease, and 19 controls. The dementia groups were matched for age, education, and general levels of cognitive and everyday functioning. Subcortical vascular dementia was defined by clinical features (prominent vascular risk factors plus a previous history of transient ischaemic events or focal neurological signs) and substantial white matter pathology on magnetic resonance imaging. All subjects were given a battery of 33 tests assessing episodic and semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. RESULTS: Despite a minimal degree of overall dementia, both patient groups had impairments in all cognitive domains. The Alzheimer patients were more impaired than those with vascular dementia on episodic memory, while the patients with vascular dementia were more impaired on semantic memory, executive/attentional functioning, and visuospatial and perceptual skills. Logistic regression analyses showed that the two groups could be discriminated with 89% accuracy on the basis of two tests, the WAIS logical memory--delayed recall test and a silhouette naming test. CONCLUSIONS: Subcortical vascular dementia and Alzheimer's disease produce distinctive profiles of cognitive impairment which can act as an adjunct to diagnosis. Many of the neuropsychological deficits thought to characterise Alzheimer's disease are also found in subcortical vascular dementia.","Aged;Alzheimer Disease/ complications/ psychology;Attention;Cognition Disorders/ etiology/ physiopathology;Dementia, Vascular/ complications/ psychology;Diagnosis, Differential;Disease Progression;Female;Humans;Male;Memory Disorders/etiology/psychology;Middle Aged;Neuropsychological Tests;Space Perception;Visual Perception","Graham, N. L.;Emery, T.;Hodges, J. R.",2004,Jan,,0,
4153,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: An unusual familial dementia. Report of a case and review of the literature [11],,sedative agent;adult;autosomal dominant disorder;brain infarction;case report;cerebral autosomal dominant arteriopathy with subcortical leukoencephalopathy;cerebrospinal fluid analysis;cerebrovascular disease;clinical feature;computer assisted tomography;delirium;differential diagnosis;female;human;hypertension;letter;leukoencephalopathy;nuclear magnetic resonance imaging;systemic lupus erythematosus,"Graham, J.;Potyk, D.",2004,,,0,
4154,Neuroimaging Correlates of Cerebral Microbleeds: The ARIC Study (Atherosclerosis Risk in Communities),"BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) location (deep versus strictly lobar) may elucidate underlying pathology with deep CMBs being more associated with hypertensive vascular disease and lobar CMBs being more associated with cerebral amyloid angiopathy. The objective of this study was to determine whether neuroimaging signs of vascular disease and Alzheimer pathology are associated with different types of CMBs. METHODS: Among 1677 nondemented ARIC (Atherosclerosis Risk in Communities) participants (mean age=76+/-5 years; 40% men; 26% black) with 3-Tesla MRI scans at the fifth examination (2011-2013), we fit multinomial logistic regression models to quantify relationships of brain volumes (Alzheimer disease signature regions, total gray matter, frontal gray matter, and white matter hyperintensity volumes), infarct frequencies (lacunar, nonlacunar, and total), and apolipoprotein E (number of epsilon4 alleles) with CMB location (none, deep/mixed, or strictly lobar CMBs). Models were weighted for the sample selection scheme and adjusted for age, sex, education, hypertension, ever smoking status, diabetes mellitus, race site membership, and estimated intracranial volume (brain volume models only). RESULTS: Deep/mixed and strictly lobar CMBs had prevalences of 8% and 16%, respectively. Larger white matter hyperintensity burden, greater total infarct frequency, smaller frontal volumes (in women only), and smaller total gray matter volume were associated with greater risk of both deep and lobar CMBs relative to no CMBs. Greater white matter hyperintensity volume was also associated with greater risk of deep relative to lobar CMBs. Higher lacunar and nonlacunar infarct frequencies were associated with higher risk of deep CMBs, whereas smaller Alzheimer disease signature region volume and apolipoprotein E epsilon4 homozygosity were associated with greater risk of lobar CMBs. CONCLUSIONS: CMBs are a common vascular pathology in the elderly. Markers of hypertensive small-vessel disease may contribute to deep CMBs while cerebral amyloid angiopathy may drive development of lobar CMBs.","Aged;Aged, 80 and over;Atherosclerosis/complications/ diagnostic imaging/ epidemiology;Cerebral Hemorrhage/ diagnostic imaging/ epidemiology/etiology;Female;Humans;Male;Middle Aged;Neuroimaging;Prospective Studies;Risk Factors;apolipoprotein E4;cerebral microbleed;intracerebral hemorrhage;magnetic resonance imaging","Graff-Radford, J.;Simino, J.;Kantarci, K.;Mosley, T. H., Jr.;Griswold, M. E.;Windham, B. G.;Sharrett, A. R.;Albert, M. S.;Gottesman, R. F.;Jack, C. R., Jr.;Vemuri, P.;Knopman, D. S.",2017,Nov,,0,
4155,"Atrial fibrillation, cognitive impairment, and neuroimaging","INTRODUCTION: The objective of our study was to investigate cross-sectional associations of atrial fibrillation with neuroimaging measures of cerebrovascular disease and Alzheimer's disease and their interactions with mild cognitive impairment (MCI). METHODS: Magnetic resonance imaging scans of individuals from a population-based study were analyzed for infarctions, total gray matter, and hippocampal and white matter hyperintensity volumes. A subsample underwent positron emission tomography imaging. RESULTS: Atrial fibrillation was associated with infarctions and lower total gray matter volume. Compared with subjects with no atrial fibrillation and no infarction, the odds ratio (95% confidence intervals) for MCI was 2.99 (1.57-5.70; P = .001) among participants with atrial fibrillation and infarction, 0.90 (0.45-1.80; P = .77) for atrial fibrillation and no infarction, and 1.50 (0.96-2.34; P = .08) for no atrial fibrillation and any infarction. DISCUSSION: Participants with both atrial fibrillation and infarction are more likely to have MCI than participants with either infarction or atrial fibrillation alone.",,"Graff-Radford, J.;Madhavan, M.;Vemuri, P.;Rabinstein, A. A.;Cha, R. H.;Mielke, M. M.;Kantarci, K.;Lowe, V.;Senjem, M. L.;Gunter, J. L.;Knopman, D. S.;Petersen, R. C.;Jack, C. R., Jr.;Roberts, R. O.",2016,Apr,10.1016/j.jalz.2015.08.164,0,
4156,"Nonhemorrhagic infarction of the thalamus: Behavioral, anatomic, and physiologic correlates","We studied five patients with nonhemorrhagic thalamic infarction with neuropsychological tests, CT, and somatosensory evoked responses (SERs). The three patients with left thalamic esions had abnormalities of language, memory, visuospatial processing, intellect, and personality - changes compatible with dementia. The two patients with right thalamic lesions were not aphasic and did not have verbal memory defects, but were otherwise comparable. Four lesions occurred in the tuberothalamic artery territory and one in the deep interpeduncular artery territory. SERs revealed a delay in the first negative peak after P14 in the tuberothalamic patients, and a delay in the third negative peak (N60) in all patients.",anatomy;behavior;case report;central nervous system;diagnosis;evoked somatosensory response;human;infarction;methodology;physiology;thalamus,"Graff Radford, N. R.;Eslinger, P. J.;Damasio, A. R.;Yamada, T.",1984,,,0,
4157,Abnormalities of the brain in AIDS patients: correlation of postmortem MR findings with neuropathology,"The ability of MR to detect CNS lesions in AIDS patients was evaluated by postmortem scanning of 10 formalin-fixed brains. Nine patients had premortem mental status changes and five had focal neurologic deficits. The brains were imaged and sectioned in corresponding planes. MR images showed atrophy in eight of the 10. All grossly identified lesions and areas of MR abnormality were histologically evaluated. Areas of infarction and necrosis associated with cytomegalovirus (CMV) or Toxoplasma gondii were seen as foci of increased signal intensity. Severe ventriculitis and focal gliosis were also visible by MR. Neither CT nor MR was able to detect diffuse CMV- or HIV-associated microglial nodules. Dementia without focal neurologic signs correlated best with the presence of diffuse microglial nodules at pathology. Our results demonstrate the usefulness of correlating postmortem MR imaging with neuropathology, and the relevance of postmortem findings to the interpretation of MR images in living patients.","Acquired Immunodeficiency Syndrome/complications/ pathology/radiography;Adult;Atrophy/pathology;Brain/ pathology/radiography;Brain Diseases/etiology/ pathology/radiography;False Negative Reactions;False Positive Reactions;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Grafe, M. R.;Press, G. A.;Berthoty, D. P.;Hesselink, J. R.;Wiley, C. A.",1990,Sep-Oct,,0,
4158,"Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with ""normal"" serum B12 levels","Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B12 levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B12 deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B12 levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B12 injections (1000 mg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B12, homocysteine and methylmalonic acid levels are unreliable predictors of B 12-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.",cyanocobalamin;fludrocortisone;midodrine;adult;anamnesis;article;autonomic dysfunction;case report;dementia;female;human;laboratory test;leukoencephalopathy;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;priority journal;vitamin blood level;vitamin supplementation,"Graber, J. J.;Sherman, F. T.;Kaufmann, H.;Kolodny, E. H.;Sathe, S.",2010,,,0,
4159,Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology,"White matter hyperintensities (WMH) are frequently seen on T(2)-weighted MRI scans of elderly subjects with and without Alzheimer's disease. WMH are only weakly and inconsistently associated with cognitive decline, which may be explained by heterogeneity of the underlying neuropathological substrates. The use of quantitative MRI could increase specificity for these neuropathological changes. We assessed whether post-mortem quantitative MRI is able to reflect differences in neuropathological correlates of WMH in tissue samples obtained post-mortem from Alzheimer's disease patients and from non-demented elderly. Thirty-three formalin-fixed, coronal brain slices from 11 Alzheimer's disease patients (mean age: 83 +/- 10 years, eight females) and 15 slices from seven non-demented controls (mean age: 78 +/- 10 years, four females) with WMH were scanned at 1.5 T using qualitative (fluid-attenuated inversion recovery, FLAIR) and quantitative MRI [diffusion tensor imaging (DTI) including estimation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA), and T(1)-relaxation time mapping based on flip-angle array). A total of 104 regions of interest were defined on FLAIR images in WMH and normal appearing white matter (NAWM). Neuropathological examination included (semi-)quantitative assessment of axonal density (Bodian), myelin density (LFB), astrogliosis (GFAP) and microglial activation (HLA-DR). Patient groups (Alzheimer's disease versus controls) and tissue types (WMH versus NAWM) were compared with respect to QMRI and neuropathological measures. Overall, Alzheimer's disease patients had significantly lower FA (P < 0.01) and higher T(1)-values than controls (P = 0.04). WMH showed lower FA (P < 0.01) and higher T(1)-values (P < 0.001) than NAWM in both patient groups. A significant interaction between patient group and tissue type was found for the T(1) measurements, indicating that the difference in T(1)-relaxation time between NAWM and WMH was larger in Alzheimer's disease patients than in non-demented controls. All neuropathological measures showed differences between WMH and NAWM, although the difference in microglial activation was specific for Alzheimer's disease. Multivariate regression models revealed that in Alzheimer's disease, axonal density was an independent determinant of FA, whereas T(1) was independently determined by axonal and myelin density and microglial activation. Quantitative MRI techniques reveal differences in WMH between Alzheimer's disease and non-demented elderly, and are able to reflect the severity of the neuropathological changes involved.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Astrocytes/pathology;Axons/pathology;Brain/ pathology;Brain Mapping/methods;Female;Humans;Image Interpretation, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Microglia/pathology;Prospective Studies","Gouw, A. A.;Seewann, A.;Vrenken, H.;van der Flier, W. M.;Rozemuller, J. M.;Barkhof, F.;Scheltens, P.;Geurts, J. J.",2008,Dec,10.1093/brain/awn265,0,
4160,"Can MRI water apparent diffusion coefficient (ADC) value discriminate between idiopathic normal pressure hydrocephalus, Alzheimer's disease and subcortical vascular dementia?","Numerous similarities in MRI and clinical symptoms exist between Alzheimer's disease (AD), subcortical vascular dementia (sVD) and possible idiopathic normal pressure hydrocephalus (iHPN). The aim of this study is to explore mean apparent coefficient diffusion (ADC) difference between theses diseases in different periventricular and deep white matter areas, as compared to healthy controls. This retrospective study analyzed mean ADC values of 120 patients in normal appearing deep white matter and lenticular nuclei, frontal, caudate nuclei corpus and parietal periventricular and deep white matter areas INPH group showed significantly lower ADC than sVD group in frontal periventricular region (1567.10(-6)mm(2)/s vs 1755.10(-6)mm(2)/s; P=0.0009) and in parietal deep region (1087.10(-6)mm(2)/s vs 1271.10(-6)mm(2)/s; P=0.0052), but showed significantly higher ADC in lenticular nuclei ROI (834.10(-6)mm(2)/s vs 753.10(-6)mm(2)/s; P=0.002). The comparison between iNPH and sVD showed a cut-off value of 1676.10(-6)mm(2)/s (sensitivity 0.70, specificity 0.77) in periventricular frontal area. INPH group, in comparison with NA group, showed significantly higher ADC in all ROIs. The iNPH group also showed significantly higher ADC than AD group in all ROIs. AD group showed significantly lower ADC than sVD group in all regions, except in normal appearing lenticular nuclei and caudate nuclei corpus deep ROI. SVD group showed significantly higher ADC than NA in all ROIs, except in normal appearing lenticular nucleus ROI. Different patterns of ADC values can differentiate between AD, sVD and iNPH, even when other MRI sequences appear morphologically similar.",Adc;Alzheimer;Normal pressure hydrocephalus;Subcortical vascular dementia,"Goujon, A.;Mejdoubi, M.;Purcell, Y.;Banydeen, R.;Colombani, S.;Arrigo, A.",2018,Feb,,0,
4161,"The ARIC-PET amyloid imaging study: Brain amyloid differences by age, race, sex, and APOE","OBJECTIVE: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE epsilon4 allele status. METHODS: Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR >1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE epsilon4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status. RESULTS: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each epsilon4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39). CONCLUSIONS: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE epsilon4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study.",,"Gottesman, R. F.;Schneider, A. L.;Zhou, Y.;Chen, X.;Green, E.;Gupta, N.;Knopman, D. S.;Mintz, A.;Rahmim, A.;Sharrett, A. R.;Wagenknecht, L. E.;Wong, D. F.;Mosley, T. H., Jr.",2016,Aug 2,10.1212/wnl.0000000000002914,0,
4162,Gender differences in stroke risk among the elderly after coronary artery surgery,"BACKGROUND: Previous studies have shown that women are at higher risk than men for stroke after coronary artery bypass graft (CABG) surgery, but gender differences in systemic atherosclerosis have not been studied adequately. We investigated gender differences in the incidence of craniocervical and ascending aortic atherosclerosis and other risk factors for stroke in elderly patients (age ≥60 yr) undergoing CABG surgery. METHODS: Data were prospectively collected on 720 patients (31.8% women) undergoing CABG surgery. All patients underwent preoperative brain magnetic resonance imaging and angiography to assess for prior cerebral infarctions, carotid artery stenosis, and intracranial arterial stenosis. Epiaortic ultrasound was performed at the time of surgery to assess for atherosclerosis of the ascending aorta. Cognitive status was measured using the Hasegawa-dementia score in all patients before surgery and on the seventh postoperative day. RESULTS: Women were older and had more hypertension and intracranial arterial stenosis than did men. Men had significantly higher rates of hyperlipidemia, peripheral vascular disease, abdominal aortic aneurysm, smoking history, severe carotid artery stenosis, and severe aortic atherosclerosis than did women. Although there were no differences in prior cerebral infarction or preoperative cognitive impairment, the rate of perioperative stroke was marginally higher in men than in women (3.9% vs 1.3%, P = 0.066). Univariate predictors of perioperative stroke were prior cerebral infarctions, ascending aortic atherosclerosis, preexisting cognitive impairment, and peripheral vascular disease. Stepwise logistic regression analysis demonstrated that significant independent predictors of perioperative stroke were prior cerebral infarctions and aortic atherosclerosis. CONCLUSIONS: These data suggest that men are more likely than women to have risk factors for stroke, including severe carotid artery stenosis, severe aortic atherosclerosis, and peripheral vascular disease. The rates of prior cerebral infarction and preoperative cognitive impairment were similar between genders. © 2007 by International Anesthesia Research Society.",,"Goto, T.;Baba, T.;Ito, A.;Maekawa, K.;Koshiji, T.",2007,May,,0,
4163,"Diffuse white-matter disease in the geriatric population. A clinical, neuropathological, and CT study","CT findings in 6 autopsy cases of subcortical arteriosclerotic encephalopathy (SAE) are reported. A diffuse area of nonhomogeneous decreased density was observed in the deep white matter of both cerebral hemispheres, together with moderate dilatation of the lateral ventricles and ragged margins. The most characteristic pathological findings at autopsy were a diffuse area of incomplete infarction containing multiple small infarcts as well as cyst formation and marked stenotic atherosclerotic changes in the medullary arteries. Clinical features included patchy mental lapses, frontal-lobe syndromes, minor motor signs, and hypertension. The authors feel that SAE or a similar disease might occur in most cases of multi-infarct dementia.","Aged;Autopsy;Brain/*pathology;Cerebral Infarction/pathology/radiography;Dementia/*pathology;Humans;Intracranial Arteriosclerosis/*pathology/radiography;Tomography, X-Ray Computed","Goto, K.;Ishii, N.;Fukasawa, H.",1981,Dec,10.1148/radiology.141.3.7302224,0,
4164,"Cerebrovascular diseases and depression: Epidemiology, mechanisms and treatment","Both cerebrovascular disease (CVD) and depression are common conditions in the elderly, and there is emerging evi-dence of a bi-directional relationship: 1) depression can cause CVD and stroke, transient ischemic attack; and 2) subcorti-cal CVD are associated with increased risk for depression. The frequency of poststroke depression is highest during the first month after the stroke, but remains high even after sev-eral years. Depression is associated with poorer functional prognosis and higher mortality after stroke. There is good evidence that severity of functional impairment, high neurot-icism, low social support as well as genetic factors are associ-ated with an increased risk for post-stroke depression. Deep white matter lesions are the most consistent imaging corre-late of depression. Potential mechanisms mediating the asso-ciation between depression and CVD are neuroinflammation and HPA-axis activation, fronto-subcortical circuit lesions, and serotonergic dysfunction. Antidepressants have dem-onstrated effect on poststroke depression in meta-analyses, and such drugs as well as vitamin B can reduce the incidence of depression in stroke survivors. In addition, serotonergic drugs may strengthen poststroke motor and cognitive re-covery, potentially through restorative mechanisms. Psycho-therapeutic strategies such as problem-solving therapy seem to be effective. There is emerging evidence that treatment of cardiovascular disease and risk-factors can reduce the risk for late-life depression, but more studies are needed to test this hypothesis.",,"Göthe, F.;Enache, D.;Wahlund, L. O.;Winblad, B.;Crisby, M.;Lökk, J.;Aarsland, D.",2012,September,,0,
4165,A young-onset frontal dementia with dramatic calcifications due to a novel CSF1R mutation,"Neuroimaging and genomic analysis greatly aid in the identification of young-onset dementia antemortem. We present the case of a 33-year-old female with a 2-year rapid decline to dementia and immobility marked by personality change, executive deficits including compulsions, attention deficit, apraxia, Parkinsonism, and pyramidal signs. She had unique and dramatic calcifications and confluent white matter changes on imaging and was found to have a novel mutation in the colony stimulating factor 1 receptor gene causing adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Here, we review ALSP and briefly discuss differential diagnoses.",,"Gore, E.;Manley, A.;Dees, D.;Appleby, B. S.;Lerner, A. J.",2016,Apr 19,10.1080/13554794.2016.1175635,0,
4166,The effects of white matter hyperintensities and amyloid deposition on Alzheimer dementia,"BACKGROUND AND PURPOSE: Elevated levels of amyloid deposition as well as white matter damage are thought to be risk factors for Alzheimer Disease (AD). Here we examined whether qualitative ratings of white matter damage predicted cognitive impairment beyond measures of amyloid. MATERIALS AND METHODS: The study examined 397 cognitively normal, 51 very mildly demented, and 11 mildly demented individuals aged 42-90 (mean 68.5). Participants obtained a T2-weighted scan as well as a positron emission tomography scan using (11)[C] Pittsburgh Compound B. Periventricular white matter hyperintensities (PVWMHs) and deep white matter hyperintensities (DWMHs) were measured on each T2 scan using the Fazekas rating scale. The effects of amyloid deposition and white matter damage were assessed using logistic regressions. RESULTS: Levels of amyloid deposition (ps < 0.01), as well as ratings of PVWMH (p < 0.01) and DWMH (p < 0.05) discriminated between cognitively normal and demented individuals. CONCLUSIONS: The amount of amyloid deposition and white matter damage independently predicts cognitive impairment. This suggests a diagnostic utility of qualitative white matter scales in addition to measuring amyloid levels.","Adult;Aged;Aged, 80 and over;*Alzheimer Disease/metabolism/pathology/physiopathology;Amyloid/*metabolism;Aniline Compounds;Female;Humans;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Positron-Emission Tomography/*methods;Severity of Illness Index;Thiazoles;White Matter/*pathology;Alzheimer's;Amyloid;Biomarkers;Myelin;Vascular;White matter","Gordon, B. A.;Najmi, S.;Hsu, P.;Roe, C. M.;Morris, J. C.;Benzinger, T. L.",2015,,10.1016/j.nicl.2015.04.017,0,
4167,Acute watershed infarcts with global cerebral hypoperfusion in symptomatic CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral angiopathy. We present a case in which a pattern of diffusion signal change compatible with bihemispheric acute watershed infarcts occurred in a symptomatic patient demonstrating global hypoperfusion. To our knowledge, watershed infarcts in the clinical presentation of CADASIL have not been previously described.",gadolinium;adult;amnesia;article;blood volume;brain blood flow;brain infarction;brain perfusion;CADASIL;case report;diffusion weighted imaging;female;human;nuclear magnetic resonance imaging;white matter,"Gordhan, A.;Hudson, B. K.",2013,,,0,
4168,"Regional distribution of white matter hyperintensities in vascular dementia, Alzheimer's disease and healthy aging","BACKGROUND: White matter hyperintensities (WMH) on MRI scans indicate lesions of the subcortical fiber system. The regional distribution of WMH may be related to their pathophysiology and clinical effect in vascular dementia (VaD), Alzheimer's disease (AD) and healthy aging. METHODS: Regional WMH volumes were measured in MRI scans of 20 VaD patients, 25 AD patients and 22 healthy elderly subjects using FLAIR sequences and surface reconstructions from a three-dimensional MRI sequence. RESULTS: The intraclass correlation coefficient for interrater reliability of WMH volume measurements ranged between 0.99 in the frontal and 0.72 in the occipital lobe. For each cerebral lobe, the WMH index, i.e. WMH volume divided by lobar volume, was highest in VaD and lowest in healthy controls. Within each group, the WMH index was higher in frontal and parietal lobes than in occipital and temporal lobes. Total WMH index and WMH indices in the frontal lobe correlated significantly with the MMSE score in VaD. Category fluency correlated with the frontal lobe WMH index in AD, while drawing performance correlated with parietal and temporal lobe WMH indices in VaD. CONCLUSIONS: A similar regional distribution of WMH between the three groups suggests a common (vascular) pathogenic factor leading to WMH in patients and controls. Our findings underscore the potential of regional WMH volumetry to determine correlations between subcortical pathology and cognitive impairment.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Atrophy;Brain Mapping;Dementia, Vascular/*pathology;Female;Frontal Lobe/pathology;Humans;Image Enhancement;*Image Processing, Computer-Assisted;*Imaging, Three-Dimensional;*Magnetic Resonance Imaging;Male;Mental Status Schedule/statistics & numerical data;Nerve Fibers, Myelinated/pathology;Netherlands;Occipital Lobe/pathology;Parietal Lobe/pathology;Psychometrics;Reference Values","Gootjes, L.;Teipel, S. J.;Zebuhr, Y.;Schwarz, R.;Leinsinger, G.;Scheltens, P.;Moller, H. J.;Hampel, H.",2004,,10.1159/000079199,0,
4169,Corpus callosum size correlates with asymmetric performance on a dichotic listening task in healthy aging but not in Alzheimer's disease,"Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that may become specifically apparent in neuropsychological tasks that tap hemispheric laterality. In the present study, we examined callosal functioning with a dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20 healthy elderly with subjective memory complaints. We found decreased performance, increased ear asymmetry, and decreased callosal size in the AD group compared to healthy elderly. As expected, in the healthy elderly, we found significant negative correlations between ear asymmetry and callosal size, specifically in the anterior and posterior callosal subareas. While the association with the posterior subareas (isthmus and splenium) points at involvement of temporal areas mediating language processing, the association with the anterior subarea (the rostrum and genu) points at involvement of frontal areas mediating attention and executive functions. Remarkably however, in contrast to the healthy elderly, callosal size was not related to ear asymmetry in the AD group. The absence of an association between callosal atrophy and ear asymmetry implies that other pathological processes, next to reduced callosal functioning, attribute to ear asymmetry in AD. Difficulties to attend specifically to the left ear during dichotic listening in some of the AD patients, points at decreased attention and executive functions and suggests that pathology of specifically the frontal areas is involved.","Aging [physiology];Alzheimer Disease [pathology] [physiopathology];Analysis of Variance;Atrophy;Auditory Perception [physiology];Corpus Callosum [anatomy & histology] [pathology] [physiology];Dichotic Listening Tests;Functional Laterality [physiology];Magnetic Resonance Imaging;Memory Disorders [pathology] [physiopathology];Mental Recall [physiology];Organ Size;Reference Values;Sex Factors;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Gootjes, L.;Bouma, A.;Strien, J. W.;Schijndel, R.;Barkhof, F.;Scheltens, P.",2006,,10.1016/j.neuropsychologia.2005.05.002,0,
4170,Clinical relevance of improved microbleed detection by susceptibility- weighted magnetic resonance imaging,"Background and Purpose- Susceptibility-weighted imaging (SWI) has been shown to be more sensitive in detecting cerebral microbleeds (MBs) than is conventional T2*-weighted gradient-recalled echo imaging (GRE). However, the clinical relevance of this improved detection in terms of associations with clinical measures and risk factors is unclear. We sought to determine whether associations of MBs with clinical characteristics, risk factors, white-matter hyperintensities, and lacunes were different on GRE versus SWI in memory clinic patients. Methods- One hundred forty-one patients presenting at our memory clinic were included and underwent clinical evaluation and a magnetic resonance imaging protocol including both GRE and SWI. Images were analyzed for numbers and locations of MBs and white-matter hyperintensities. In a subset of patients, apolipoprotein E status was determined. Negative binomial regression was used to assess clinical and radiologic associations with MB number. Results- MB prevalence was 23% on GRE and 40% on SWI. A total of 219 and 284 MBs were detected on GRE and SWI, respectively. Within groups with MBs, the median MB count was 1 (range, 1 to 144) on GRE and 2 (range, 1 to 129) on SWI (P<0.001). The increase in the number of MBs on SWI was equally distributed among brain regions. Strengths of the associations with age, sex, white-matter hyperintensities, and presence of lacunes with higher MB numbers were comparable for GRE and SWI (all P<0.05); no differential independent associations were detected. Conclusions- SWI detected more MBs in more patients, irrespective of MB location. However, this enhanced detection had no improved clinical relevance in terms of associations with vascular risk factors or radiologic markers of small-vessel disease. Copyright © 2011 American Heart Association. All rights reserved.",,"Goos, J. D. C.;Van Der Flier, W. M.;Knol, D. L.;Pouwels, P. J. W.;Scheltens, P.;Barkhof, F.;Wattjes, M. P.",2011,July,,0,
4171,Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition,"BACKGROUND AND PURPOSE: Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. METHODS: Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. RESULTS: Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. CONCLUSIONS: Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.","Aged;Aged, 80 and over;Alzheimer Disease/*cerebrospinal fluid/complications/psychology;Biomarkers/cerebrospinal fluid;Case-Control Studies;Cerebral Hemorrhage/*cerebrospinal fluid/complications/psychology;Cognition Disorders/*cerebrospinal fluid/complications/psychology;Female;Humans;Male;Microcirculation;Retrospective Studies","Goos, J. D.;Kester, M. I.;Barkhof, F.;Klein, M.;Blankenstein, M. A.;Scheltens, P.;van der Flier, W. M.",2009,Nov,10.1161/strokeaha.109.558197,0,
4172,Cranial computed tomography in the diagnosis of systemic lupus erythematosus,"The cranial computed tomograms of 29 patients with systemic lupus erythematosus (SLE) were reviewed. Twenty-two patients had a clinical course consistent with central nervous system involvement. Of these, 20 had abnormal CT studies during the course of their CNS symptoms. The most common finding was sulcal enlargement, either with or without ventricular enlargement, and it was prominent in patients with either psychosis or dementia. Infarcts and intracranial hemorrhages were seen as well. Seven CT studies were obtained in SLE patients without a clear diagnosis of CNS involvement. Only one of these was abnormal.","Adolescent;Adult;Atrophy;Brain/*radiography;Cerebral Hemorrhage/complications;Cerebral Infarction/complications;Humans;Lupus Erythematosus, Systemic/complications/*diagnosis;Mental Disorders/complications;Middle Aged;Neurologic Manifestations;Tomography, X-Ray Computed","Gonzalez-Scarano, F.;Lisak, R. P.;Bilaniuk, L. T.;Zimmerman, R. A.;Atkins, P. C.;Zweiman, B.",1979,Feb,10.1002/ana.410050209,0,
4173,The impact of silent vascular brain burden in cognitive impairment in Parkinson's disease,"BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) detected by magnetic resonance imaging (MRI) of the brain are associated with dementia and cognitive impairment in the general population and in Alzheimer's disease. Their effect in cognitive decline and dementia associated with Parkinson's disease (PD) is still unclear. METHODS: We studied the relationship between WMHs and cognitive state in 111 patients with PD classified as cognitively normal (n = 39), with a mild cognitive impairment (MCI) (n = 46) or dementia (n = 26), in a cross-sectional and follow-up study. Cognitive state was evaluated with a comprehensive neuropsychological battery, and WMHs were identified in FLAIR and T2-weighted MRI. The burden of WMHs was rated using the Scheltens scale. RESULTS: No differences in WMHs were found between the three groups in the cross-sectional study. A negative correlation was observed between semantic fluency and the subscore for WMHs in the frontal lobe. Of the 36 non-demented patients re-evaluated after a mean follow-up of 30 months, three patients converted into MCI and 5 into dementia. Progression of periventricular WMHs was associated with an increased conversion to dementia. A marginal association between the increase in total WMHs burden and worsening in the Mini Mental State Examination was encountered. CONCLUSIONS: White matter hyperintensities do not influence the cognitive status of patients with PD. Frontal WMHs have a negative impact on semantic fluency. Brain vascular burden may have an effect on cognitive impairment in patients with PD as WMHs increase overtime might increase the risk of conversion to dementia. This finding needs further confirmation in larger prospective studies.",Aged;Brain/blood supply/ pathology;Cognition Disorders/ etiology/ pathology;Cross-Sectional Studies;Dementia/pathology;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/pathology;Neuropsychological Tests;Parkinson Disease/ complications/ pathology,"Gonzalez-Redondo, R.;Toledo, J.;Clavero, P.;Lamet, I.;Garcia-Garcia, D.;Garcia-Eulate, R.;Martinez-Lage, P.;Rodriguez-Oroz, M. C.",2012,Aug,10.1111/j.1468-1331.2012.03682.x,0,
4174,Peripheral sphingolipids are associated with variation in white matter microstructure in older adults,"Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging.",Ceramides;Dti;Fractional anisotropy;Sphingolipids;Sphingomyelin;White matter,"Gonzalez, C. E.;Venkatraman, V. K.;An, Y.;Landman, B. A.;Davatzikos, C.;Ratnam Bandaru, V. V.;Haughey, N. J.;Ferrucci, L.;Mielke, M. M.;Resnick, S. M.",2016,Jul,10.1016/j.neurobiolaging.2016.04.008,0,
4175,Hypertension is related to the microstructure of the corpus callosum: the RUN DMC study,"Vascular factors play a role in the etiology of Alzheimer's disease (AD), presumably due to emergence of white matter lesions. However, important white matter structures involved in the etiology of AD, including the corpus callosum (CC), remain invariably free from macroscopical white matter lesions, although loss of microstructural integrity assessed with diffusion tensor imaging (DTI) has been described in the CC. Vascular factors have been related to these microstructural white matter changes too, but little is known about their effect on the CC. In 499 subjects with cerebral small vessel disease, aged 50-85 years, we cross-sectionally investigated the relation between hypertension, hypertension treatment status, the microstructural integrity of the CC using DTI, and the attendant cognitive performance. Fractional anisotropy and mean diffusivity were calculated in four substructures of the CC (genu, anterior body, posterior body, and splenium). Differences between groups were calculated with analysis of variance, adjusted for age, gender, and cardiovascular risk factors. Compared with normotensive subjects, hypertensive subjects had a lower fractional anisotropy in the splenium and a significant higher mean diffusivity in both the anterior body and the splenium; this was most noticeable in treated uncontrolled hypertensive subjects. Furthermore we found that microstructural integrity of the CC was related to global cognition. Of this relation, 14 to 60% was explained by the mediating effect of small vessel disease elsewhere in the white matter. Our findings indicate that adequate blood pressure treatment might postpone these changes and the attendant cognitive dysfunction.","Aged;Aged, 80 and over;Cognition Disorders/epidemiology/metabolism/ pathology;Cohort Studies;Corpus Callosum/metabolism/ pathology;Diffusion Tensor Imaging/methods;Female;Humans;Hypertension/epidemiology/metabolism/ pathology;Male;Middle Aged;Nerve Fibers, Myelinated/metabolism/ pathology;Netherlands/epidemiology;Neuropsychological Tests;Prospective Studies","Gons, R. A.;van Oudheusden, L. J.;de Laat, K. F.;van Norden, A. G.;van Uden, I. W.;Norris, D. G.;Zwiers, M. P.;van Dijk, E.;de Leeuw, F. E.",2012,,10.3233/jad-2012-121006,0,
4176,Cigarette smoking is associated with reduced microstructural integrity of cerebral white matter,"Cigarette smoking doubles the risk of dementia and Alzheimer's disease. Various pathophysiological pathways have been proposed to cause such a cognitive decline, but the exact mechanisms remain unclear. Smoking may affect the microstructural integrity of cerebral white matter. Diffusion tensor imaging is known to be sensitive for microstructural changes in cerebral white matter. We therefore cross-sectionally studied the relation between smoking behaviour (never, former, current) and diffusion tensor imaging parameters in both normal-appearing white matter and white matter lesions as well as the relation between smoking behaviour and cognitive performance. A structured questionnaire was used to ascertain the amount and duration of smoking in 503 subjects with small-vessel disease, aged between 50 and 85 years. Cognitive function was assessed with a neuropsychological test battery. All subjects underwent 1.5 Tesla magnetic resonance imaging. Using diffusion tensor imaging, fractional anisotropy and mean diffusivity were calculated in both normal-appearing white matter and white matter lesions. A history of smoking was associated with significant higher values of mean diffusivity in normal-appearing white matter and white matter lesions (P-trend for smoking status = 0.02) and with poorer cognitive functioning compared with those who never smoked. Associations with smoking and loss of structural integrity appeared to be strongest in normal-appearing white matter. Furthermore, the duration of smoking cessation was positively related to lower values of mean diffusivity and higher values of fractional anisotropy in normal-appearing white matter [beta = -0.004 (95% confidence interval -0.007 to 0.000; P = 0.03) and beta = 0.019 (95% confidence interval 0.001-0.038; P = 0.04)]. Fractional anisotropy and mean diffusivity values in normal-appearing white matter of subjects who had quit smoking for >20 years were comparable with subjects who had never smoked. These data suggest that smoking affects the microstructural integrity of cerebral white matter and support previous data that smoking is associated with impaired cognition. Importantly, they suggest that quitting smoking may reverse the impaired structural integrity.","Aged;Analysis of Variance;Anisotropy;Blood Pressure/physiology;Cerebral Cortex/ pathology;Cognition Disorders/etiology/pathology;Cohort Studies;Diffusion Tensor Imaging/methods;Female;Heart Rate/physiology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Risk Factors;Smoking/ pathology/therapy;Smoking Cessation/methods","Gons, R. A.;van Norden, A. G.;de Laat, K. F.;van Oudheusden, L. J.;van Uden, I. W.;Zwiers, M. P.;Norris, D. G.;de Leeuw, F. E.",2011,Jul,10.1093/brain/awr145,0,
4177,Physical activity is related to the structural integrity of cerebral white matter,"OBJECTIVE: To investigate the relation between physical exercise and the microstructural integrity of cerebral white matter. METHODS: Four hundred forty individuals with cerebral small-vessel disease, aged between 50 and 85 years, without dementia, were included and underwent MRI scanning. Physical exercise was assessed with a structured questionnaire. The cross-sectional relation between physical exercise and the microstructural integrity of the white matter was assessed by applying Tract-Based Spatial Statistics to diffusion tensor imaging parameters. RESULTS: Being more physically active was negatively related to the mean, axial, and radial diffusivity in numerous regions of the white matter, indicative of higher white matter integrity. CONCLUSIONS: These data indicate an association between physical activity and the integrity of the cerebral white matter's microstructure. Prospective studies are required to investigate a possible causal association between physical activity and cognitive decline.","Aged;Aged, 80 and over;Cerebral Small Vessel Diseases/ pathology/ physiopathology;Cerebrum/ pathology;Chi-Square Distribution;Cross-Sectional Studies;Diffusion Tensor Imaging;Exercise/ physiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Surveys and Questionnaires","Gons, R. A.;Tuladhar, A. M.;de Laat, K. F.;van Norden, A. G.;van Dijk, E. J.;Norris, D. G.;Zwiers, M. P.;de Leeuw, F. E.",2013,Sep 10,10.1212/WNL.0b013e3182a43e33,0,
4178,White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals,"Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.",,"Gongvatana, A.;Schweinsburg, B. C.;Taylor, M. J.;Theilmann, R. J.;Letendre, S.;Alhassoon, O. M.;Jacobus, J.;Woods, S. P.;Jernigan, T. L.;Ellis, R. J.;Frank, L. R.;Grant, I.",2009,2009,,0,
4179,Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: A diffusional kurtosis imaging study,"Object: Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency. Materials and Methods: DKI was performed on 18. AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann-Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation. Results: In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM. Conclusion: Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM. © 2013 Elsevier Inc.",,"Gong, N. J.;Wong, C. S.;Chan, C. C.;Leung, L. M.;Chu, Y. C.",2013,2013,,0,
4180,Clinical and genetic features in a family with CADASIL and high lipoprotein (a) values,"We present a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and elevated lipoprotein(a) [Lp(a)] levels. In addition to neurological examinations, ultrasound of extra- and intracranial arteries, laboratory tests, and cerebral magnetic resonance imaging (MRI), a whole genome screening with mutation analyses was performed. Rather untypical for CADASIL, stenoses of large intracranial arteries were detected in the index patient. All affected subjects lacked a history of migraine, mood disturbances, and cognitive decline despite extensive white matter lesions in two individuals. Furthermore, evidence of early cerebral microangiopathy was demonstrated in three children (age 9, 11 and 13). We were able to explain the mechanism of elevated Lp(a) on the basis of the kringle IV type 2 repetition size. A mutation S118C located in exon 4 of Notch3 was responsible for CADASIL. Elevated Lp(a) might have contributed to the cerebrovascular phenotype in this family. © 2010 Springer-Verlag.",,"Gong, M.;Rueschendorf, F.;Marx, P.;Schulz, H.;Kraft, H. G.;Huebner, N.;Koennecke, H. C.",2010,August,,0,
4181,Recent progress on small vessel disease with cognitive impairment,"Vascular cognitive impairment (VCI) refers to different degrees of cognitive dysfunction syndrome caused by all kinds of cerebral vascular disease and vascular factors. Before in the development of vascular dementia (VaD), early diagnosis and intervention can prevent and delay the progress of VCI, even reverse cognitive impairment. In this review, we summarized the research progress of vascular cognitive impairment in pathophysiology, biomarkers and treatments, etc.",apolipoprotein E;C reactive protein;interleukin 6;microRNA;neopterin;nimodipine;Notch3 receptor;tumor necrosis factor alpha;article;blood brain barrier;brain hemorrhage;brain infarction;cerebrovascular disease;clinical feature;cognitive defect;comorbidity;computer assisted tomography;diffusion weighted imaging;disease association;human;multiinfarct dementia;nervous system inflammation;neuroimaging;nuclear magnetic resonance imaging;white matter lesion,"Gong, L.;Liu, X. Y.;Fang, M.",2015,,,0,
4182,Prevalence of functional cognitive impairment and associated factors in Brazilian community-dwelling older adults,"The identification of the prevalence of cognitive impairment and associated factors among older adults is important in countries facing rapid demographic transition, given the significant implications for public policy and health planning. Objective: To determine the prevalence of functional cognitive impairment (FCI) and associated factors in Brazilian community-dwelling older adults. Methods: A cross-sectional study involving 461 elderly subjects residing in Fortaleza city, Ceara was conducted. Cognitive assessment was performed using three tests: the MMSE (Mini-Mental State Examination), VF (Verbal Fluency) and CT (Clock Test). The functional capacity evaluation was based on a survey of 21 basic and instrumental activities of daily living (ADLs). Cognitive impairment was defined by MMSE cut-off points adjusted for literacy. Functional impairment was defined as dependency to carry out more than four ADLs. Results: The prevalence of FCI was 13.64% (95% CI: 10.33 to 16.64%). FCI was proportionally associated with age with OR=2.24 (95% CI: 1.04 to 4.79) for individuals aged 70 to 79 years and OR=8.27 (95 % CI: 4.27 to 16.4) for those aged 80 to 100 years. FCI was associated with self-reported diseases including hypertension OR=2.06 (95% CI: 1.17 to 3.65), stroke OR=2.88 (95% CI: 1.66 to 5.00) and acute myocardial infarction OR=2.94 (95% CI: 1.59 to 5.42). The occurrence of FCI was proportionally correlated with the number of drugs used. Conclusion: Functional cognitive impairment is a prevalent condition in Brazilian community-dwelling older adults and its occurrence is associated with age, number of drugs used, and vascular morbidities.",aging;dementia;elderly;epidemiology;prevalence,"Gondim, A. S.;Coelho Filho, J. M.;Cavalcanti, A. A.;Roriz Filho, J. S.;Nogueira, C. B.;Peixoto Junior, A. A.;Lima, J. W. O.",2017,Jan-Mar,,0,
4183,Dementia associated with the antiphospholipid syndrome: Clinical and radiological characteristics of 30 patients,"Objective. To analyse the clinical and radiological characteristics of patients with dementia associated with the antiphospholipid syndrome (APS). Methods. Twenty-five patients were identified by a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of dementia associated with APS published in English, Spanish and French from 1983 to 2003. Additionally, we included five patients from our clinics. Results. There were 21 (70%) females and 9 (30%) males. The mean age of patients was 49±15 yr (range 16-79 yr). Fourteen (47%) of the patients suffered from primary APS, 9 (30%) had systemic lupus erythematosus and 7 (23%) had 'lupus-like' syndrome. Ten (33%) patients had Sneddon's syndrome and 2 (7%) had cerebral lesions described as Binswanger's disease. Other APS-related manifestations included thrombocytopenia in 12 (40%) patients, cerebrovascular accidents in 11 (37%), heart valve lesions in 8 (27%), deep vein thrombosis in 7 (28%), migraine in 7 (23%), seizures in 4 (13%); five of the 21 (24%) female patients had nine spontaneous abortions. Lupus anticoagulant was present in 21/29 (72%) patients and anticardiolipin antibodies were present in 24/29 (83%) patients. Cortical infarcts were found in 19 (63%) patients, subcortical infarcts in 9 (30%), basal ganglia infarcts in 7 (23%) and signs of cerebral atrophy in 11 (37%). Anticoagulation was used in 14/25 (56%) patients, steroids in 12/25 (48%), aspirin in 6/25 (24%) and dypiridamole in 5/25 (20%). Conclusions. Dementia is an unusual manifestation of APS but one which has a high disability impact in a patient's daily life. In order to prevent these consequences, an echocardiographic and cerebral CT or MRI evaluation are recommended in all patients with APS. Furthermore, ruling out APS should be recommended in the clinical approach to dementia, especially in young patients. © British Society for Rheumatology 2004; all rights reserved.",acetylsalicylic acid;cardiolipin antibody;dipyridamole;lupus anticoagulant;steroid;adolescent;adult;aged;anticoagulant therapy;antiphospholipid syndrome;article;basal ganglion;Binswanger encephalopathy;brain atrophy;brain infarction;cerebrovascular accident;clinical article;clinical feature;computer analysis;computer assisted tomography;controlled study;daily life activity;deep vein thrombosis;dementia;disability;echocardiography;female;human;lupus erythematosus;male;medical literature;Medline;migraine;nuclear magnetic resonance imaging;priority journal;publication;radiodiagnosis;seizure;Sneddon syndrome;spontaneous abortion;systemic lupus erythematosus;thrombocytopenia;valvular heart disease;aspirin,"Gómez-Puerta, J. A.;Cervera, R.;Calvo, L. M.;Gómez-Ansón, B.;Espinosa, G.;Claver, G.;Bucciarelli, S.;Bové, A.;Ramos-Casals, M.;Ingelmo, M.;Font, J.",2005,,,0,
4184,Regarding long-term statin therapy: Are we trading stronger hearts for weaker brains?,"Ideally, the benefits of long-term statin therapy should outweigh the risks in all populations. However, some data suggest that long-term statin therapy might promote cerebral small vessel disease and impair myelination, perhaps resulting from cholesterol depletion and pleiotropic effects on amyloid-β metabolism and oligodendrocyte function. The clinical ramifications can be problematic and have a negative impact on the quality of life. Questions are proposed and the answers should be found by analysis of randomized prospective trials specifically investigating the effects of statin therapy on brain structure and function. Those trials should not be funded by drug companies and the investigators should not have financial ties to the pharmaceutical industry. The relevance of the aforementioned is amplified in light of the new cardiovascular guidelines that might culminate in more than a billion people receiving statin therapy worldwide. © 2014 Elsevier Ltd.",3 hydroxy 3 methylglutaryl coenzyme A;amyloid beta protein[1-40];amyloid precursor protein;apolipoprotein E2;apolipoprotein E4;cholesterol;geranylgeranyl pyrophosphate;hydroxymethylglutaryl coenzyme A reductase inhibitor;myelin;aging;allele;article;blood brain barrier;blood vessel wall;brain hypoxia;brain infarction;cerebrovascular disease;clinical feature;dementia;disease association;human;lacunar stroke;leukoaraiosis;long term care;meta analysis (topic);mortality;nerve conduction;neuropathology;neurotoxicity;nuclear magnetic resonance imaging;oligodendroglia;Schwann cell;sporadic cerebral amyloid angiopathy;vascular amyloidosis;white matter lesion,"Goldstein, M. R.;Mascitelli, L.",2014,,,0,
4185,[Vascular dementia: big effects of small lesions] Demence vasculaire: les grands effets des petites lesions,"Vascular dementia due to multiple large strokes (multi-infarct dementia) is a well known entity. However, new clinicopathologic and neuroimaging data have highlighted the common occurrence of small vessel and microscopic vascular pathology in aging brains and recognized that vascular dementia due to small lesions is probably the most common form. In such cases, cortical microinfarcts are the strongest correlate of global cognitive function followed by basal ganglia and thalamic lacunes. Demyelination is only weekly associated with cognition and this relation is no longer significant after adjustement for the presence of lacunes. Awareness of the importance of small vascular lesions in brain aging, can improve diagnostic accuracy and help identify new targets, that could lead to novel therapeutic approaches in old age dementia.","Aging/ pathology;Brain Infarction/ pathology;Dementia, Vascular/ diagnosis;Demyelinating Diseases/pathology;Humans;Magnetic Resonance Imaging","Gold, G.;Kovari, E.",2011,Nov 09,,0,
4186,[Vascular dementia: big effects of small lesions],"Vascular dementia due to multiple large strokes (multi-infarct dementia) is a well known entity. However, new clinicopathologic and neuroimaging data have highlighted the common occurrence of small vessel and microscopic vascular pathology in aging brains and recognized that vascular dementia due to small lesions is probably the most common form. In such cases, cortical microinfarcts are the strongest correlate of global cognitive function followed by basal ganglia and thalamic lacunes. Demyelination is only weekly associated with cognition and this relation is no longer significant after adjustement for the presence of lacunes. Awareness of the importance of small vascular lesions in brain aging, can improve diagnostic accuracy and help identify new targets, that could lead to novel therapeutic approaches in old age dementia.","Aging/*pathology;Brain Infarction/*pathology;Dementia, Vascular/*diagnosis;Demyelinating Diseases/pathology;Humans;Magnetic Resonance Imaging","Gold, G.;Kovari, E.",2011,Nov 9,,0,
4187,White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults,"We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ(42) and Aβ(42)/p-Tau(181)) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower",,"Gold, B. T.;Zhu, Z.;Brown, C. A.;Andersen, A. H.;LaDu, M. J.;Tai, L.;Jicha, G. A.;Kryscio, R. J.;Estus, S.;Nelson, P. T.;Scheff, S. W.;Abner, E.;Schmitt, F. A.;Van Eldik, L. J.;Smith, C. D.",2014,October,,0,
4188,Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease,"There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging data [including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA) and radial diffusivity (DR)] and volumetric comparisons of medial temporal lobe (MTL) structures were conducted. Results indicated equivalent entorhinal cortex and hippocampal volumes between risk groups. Nevertheless, the high risk group showed decreased microstructural integrity in WM tracts with direct and secondary connections to the MTL. The predominant alteration in WM integrity in the high AD-risk group was decreased FA not solely driven by either DA or DR changes alone in regions where no MD changes were observed. A second pattern observed in a smaller number of regions involved decreased FA and increased DR. These results suggest that disconnection of MTL-neocortical fiber pathways represents a very early event in the course of AD and suggest that demyelination may represent one contributing mechanism.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Middle Aged;Nerve Fibers, Myelinated/ pathology;Prognosis;Reference Values;Risk Factors","Gold, B. T.;Powell, D. K.;Andersen, A. H.;Smith, C. D.",2010,Oct 1,10.1016/j.neuroimage.2010.05.036,0,
4189,Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild cognitive impairment,"White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection. © 2012 - IOS Press and the authors. All rights reserved.",myelin;aged;article;clinical article;controlled study;female;fractional anisotropy;gray matter;hippocampus;human;male;mild cognitive impairment;nerve fiber;neuroimaging;nuclear magnetic resonance imaging;parahippocampal gyrus;parietal cortex;precuneus;priority journal;temporal lobe;white matter,"Gold, B. T.;Jiang, Y.;Powell, D. K.;Smith, C. D.",2012,,10.3233/jad-2012-112165,0,4190
4190,Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild cognitive impairment,"White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection.","Aged;Amnesia/ pathology/psychology;Anisotropy;Atrophy;Axons/ pathology;Brain/pathology;Demography;Diffusion Tensor Imaging/methods;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/ pathology/psychology;Myelin Sheath/ pathology;Neuropsychological Tests;ROC Curve","Gold, B. T.;Jiang, Y.;Powell, D. K.;Smith, C. D.",2012,,10.3233/jad-2012-112165,0,
4191,Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults,"Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer's disease (AD) pathology and cerebral white-matter hyperintensities (WMHs). Twenty-nine younger adults and 34 cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging was performed. Older adults further underwent lumbar cerebrospinal fluid draw for the assessment of AD pathology and FLAIR imaging for the assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked with lower levels of clinically silent AD pathology. In addition, AD pathology and WMHs were each independently related to increased functional magnetic resonance imaging response in the left dorsolateral prefrontal cortex, a pattern associated with slower task performance. Our results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance. Further, our findings suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/ pathology/ physiopathology;Brain/diagnostic imaging/ physiology/ physiopathology;Executive Function/ physiology;Female;Healthy Aging/ physiology/psychology;Humans;Magnetic Resonance Imaging;Male;Memory;Nerve Net/ physiology/ physiopathology;White Matter/ diagnostic imaging/ pathology;Young Adult;Aging;Alzheimer's;Connectivity;Executive;Hyperintensities","Gold, B. T.;Brown, C. A.;Hakun, J. G.;Shaw, L. M.;Trojanowski, J. Q.;Smith, C. D.",2017,Oct,,0,
4192,Usefulness of Follow-up Regional Cerebral Blood Flow Measurements by Single-Photon Emission Computed Tomography in the Differential Diagnosis of Dementia,"The aim of this study was to evaluate whether follow-up measurements of regional cerebral blood flow (rCBF) by single-photon emission computed tomography (SPECT) provide additional information in the differential diagnosis of dementia. Thirty-six patients (70 ± 14 yr) with suspected dementia who had two technetium 99m-hexamethylpropyleneamineoxime SPECT scans over 18 ± 7 months were included in this retrospective study. The patients comprised three groups based on the final clinical diagnosis: (1) neurodegenerative disorder (NDD) including Alzheimer's disease (AD) (n = 13), frontotemporal lobe dementia (n = 2), progressive supranuclear palsy (n = 1 ), and mixed dementia (AD plus multi infarct dementia [MID]) (n = 3); (2) MID (n = 8); and (3) psychiatric disorders (depression [n = 7]. psychosis [n = 1]. and anxiety [n = 1 ]). Blinded to the clinical diagnosis and using visual analysis, the nuclear medicine physicians compared the second scan with the first scan for each patient to characterize temporal changes in rCBF. SPECT findings were categorized into three patterns of rCBF change: worsened, improved, and unchanged. Of the worsened rCBF group, 17 (85%) belonged to the NDD group whereas 2 (1 0%) and 1 (5%) belonged to the MID and psychiatric disorders groups, respectively. All 5 (1 00%) of the improved rCBF patients belonged to the psychiatric disorders group. Thus, worsening of rCBF favors the diagnosis of NDD whereas improvement in rCBF may mitigate against the diagnosis of NDD or MID. Follow-up rCBF measurements by SPECT thus provided additional information on the possible cause of dementia. A prospective study to further evaluate the usefulness of follow-up rCBF measurements by SPECT appears warranted.",hexamethylpropylene amine oxime technetium tc 99m;aged;Alzheimer disease;article;blood flowmetry;brain blood flow;clinical article;controlled study;dementia;differential diagnosis;female;follow up;frontotemporal dementia;gamma camera;human;male;mental disease;multiinfarct dementia;neuroimaging;progressive supranuclear palsy;retrospective study;single photon emission computer tomography;SPECT scanner,"Golan, H.;Kremer, J.;Freedman, M.;Ichise, M.",1996,,,0,
4193,Joint effect of white matter lesions and hippocampal volumes on severity of cognitive decline: the 3C-Dijon MRI study,"Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.","Aged;Aged, 80 and over;Cognition Disorders/ pathology;Female;Hippocampus/ pathology;Humans;Imaging, Three-Dimensional/methods;Linear Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Retrospective Studies;Severity of Illness Index","Godin, O.;Tzourio, C.;Rouaud, O.;Zhu, Y.;Maillard, P.;Pasquier, F.;Crivello, F.;Alperovitch, A.;Mazoyer, B.;Dufouil, C.",2010,,10.3233/jad-2010-1389,0,
4194,Antihypertensive treatment and change in blood pressure are associated with the progression of white matter lesion volumes: the Three-City (3C)-Dijon Magnetic Resonance Imaging Study,"BACKGROUND: Blood pressure (BP) is recognized as a major risk factor for white matter lesions (WMLs), but longitudinal data are scarce, and there is insufficient evidence for the benefit of antihypertensive therapy on WML progression. We studied the relationship between BP change and WML volume progression over time in a sample of 1319 elderly individuals who had 2 cerebral magnetic resonance imaging examinations 4 years apart. We also examined the impact of antihypertensive treatment on WML progression. METHODS AND RESULTS: Subjects were participants from the Three-City (3C)-Dijon Magnetic Resonance Imaging Study, a prospective population-based cohort of elderly >/= 65 years of age. WML volumes and their progression were estimated with the use of a fully automatic procedure. We performed ANCOVA models first to assess the association between BP change and WML progression and second to estimate the relation between antihypertensive treatment and WML load progression. Baseline and change in BP were significant predictors of higher WML progression over time after controlling for potential confounders. Among subjects with high SBP (>/= 160 mm Hg) at baseline not treated by antihypertensive medication, antihypertensive treatment started within 2 years was related to a smaller increase in WML volume at a 4-year follow-up (0.24 cm(3); SE=0.44 cm(3)) than no hypertensive treatment (1.60 cm(3); SE = 0.26 cm(3); P = 0.0008) on multivariable modeling. CONCLUSIONS: Our findings reinforce the hypothesis that hypertension is a strong predictor of WML and that adequate treatment may reduce the course of WML progression. Because WMLs are linked to both dementia and stroke risks, these results could have implications for future preventive trials.","Aged;Aged, 80 and over;Aging;Antihypertensive Agents/ therapeutic use;Blood Pressure/ drug effects;Cross-Sectional Studies;Disease Progression;Female;Follow-Up Studies;Humans;Hypertension/ drug therapy/ epidemiology;Leukoencephalopathies/ epidemiology/pathology;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Predictive Value of Tests;Risk Factors","Godin, O.;Tzourio, C.;Maillard, P.;Mazoyer, B.;Dufouil, C.",2011,Jan 25,10.1161/circulationaha.110.961052,0,
4195,Apolipoprotein E genotype is related to progression of white matter lesion load,"BACKGROUND AND PURPOSE: The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment. METHODS: The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression. RESULTS: Multivariable analyses showed that epsilon4epsilon4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon4 allele for apolipoprotein E genotype. CONCLUSION: These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia.","Aged;Aged, 80 and over;Apolipoprotein E4/genetics;Apolipoproteins E/*genetics;Brain/metabolism/*pathology/physiopathology;Cohort Studies;DNA Mutational Analysis;Dementia/*genetics/*pathology/physiopathology;Disease Progression;Female;Genetic Predisposition to Disease/*genetics;Genetic Testing;Genotype;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Polymorphism, Genetic/genetics;Severity of Illness Index","Godin, O.;Tzourio, C.;Maillard, P.;Alperovitch, A.;Mazoyer, B.;Dufouil, C.",2009,Oct,10.1161/strokeaha.109.555839,0,
4196,Association of white-matter lesions with brain atrophy markers: The three-city Dijon MRI study,"Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1,792 elderly subjects aged 65-80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM (β = -0.03, p < 0.0001) and hippocampal volumes (β = -0.75, p = 0.0009) and positively with CSF volumes (β = 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of nondemented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors. Copyright © 2009 S. Karger AG.",apolipoprotein E;age;aged;article;brain atrophy;brain degeneration;brain size;cerebrospinal fluid;cerebrovascular disease;education;female;France;gender;gray matter;hippocampus;human;hypertension;major clinical study;male;nuclear magnetic resonance imaging;priority journal;risk factor;vascular disease;white matter,"Godin, O.;Maillard, P.;Crivello, F.;Alpérovitch, A.;Mazoyer, B.;Tzourio, C.;Dufouil, C.",2009,,,0,
4197,Multiple simultaneous cerebral infarctions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,,adult;anamnesis;article;blood pressure;brain infarction;CADASIL;case report;clinical feature;diagnostic procedure;diffusion weighted imaging;disease association;female;human;leukoencephalopathy;male;nuclear magnetic resonance imaging;priority journal;risk factor,"Gobron, C.;Viswanathan, A.;Bousser, M. G.;Chabriat, H.",2006,,,0,
4198,Characteristic features of in vivo skin microvascular reactivity in CADASIL,"CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by mutations in the Notch3 receptor expressed at the surface of vascular smooth muscle cells. The functional consequences of the disease at the peripheral microcirculation level are incompletely elucidated. In this study, we aimed to assess, in vivo, the endothelium-dependent and independent vasodilation of the skin microvasculature in CADASIL patients. Twenty-three affected subjects were compared with 23 gender and age-matched controls. The brachial artery endothelium-dependent and endothelium-independent vasodilation were assessed after forearm cuff occlusion and nitroglycerin administration. Skin vasoreactivity to transcutaneous administration of acetylcholine and sodium nitroprussiate, and after postocclusive hyperemia were measured by Laser Doppler flowmetry. The maximum changes in the diameter of the brachial artery after the cuff release or after nitroglycerin administration did not differ between patients and controls. With iontopheresis, only the peak value of the dose response was found decreased in normocholesterolemic patients after nitroprussiate administration. The postocclusive test revealed a large increase of the time to peak value and whole duration of the hyperemic response in CADASIL patients. The results of this study show that the skin vasoreactivity is altered in CADASIL. Particularly, the kinetics of reactive hyperemia after cuff occlusion is dramatically changed with a lengthened and delayed response. This characteristic pattern may be related to the specific ultrastructural modifications related to Notch3 gene mutations involving smooth muscle cells in the microvasculature.","Adult;Aged;Brachial Artery/physiology;CADASIL/*physiopathology;Dose-Response Relationship, Drug;Female;Humans;Hyperemia/physiopathology;Magnetic Resonance Imaging;Male;Microcirculation/physiology;Middle Aged;Nitroprusside/pharmacology;Regional Blood Flow/physiology;Skin/*blood supply;Vasodilation/physiology;Vasodilator Agents/pharmacology","Gobron, C.;Vahedi, K.;Vicaut, E.;Stucker, O.;Laemmel, E.;Baudry, N.;Bousser, M. G.;Chabriat, H.",2007,Feb,10.1038/sj.jcbfm.9600356,0,
4199,[Cerebral microbleeds] Microbleeds cerebraux,"Microbleedscorrespond to small areas of hypointense signals on MRI T2 sequences of the brain. Their presence is correlated with age and hypertension. They are frequently associated with lacunae and with hyperintense (bright) signals in white matter. Microbleeds are associated with local deposits of blood decay products and are a marker of cerebral microangiopathy, most often lipohyalinosis. They are frequently observed in ischemic neurovascular disease, especially lacunar and hemorrhagic. They may thus have prognostic value. Microbleeds are often present in dementia, especially vascular dementia. The therapeutic consequences of the discovery of microbleeds remain very uncertain, especially in terms of the use of antithrombotic agents.",Cerebral Hemorrhage/complications/diagnosis/etiology;Humans;Magnetic Resonance Imaging;Microvessels;Risk Factors,"Goas, P.;Timsit, S.",2010,Jun,,0,
4200,[Cerebral microbleeds],"Microbleedscorrespond to small areas of hypointense signals on MRI T2 sequences of the brain. Their presence is correlated with age and hypertension. They are frequently associated with lacunae and with hyperintense (bright) signals in white matter. Microbleeds are associated with local deposits of blood decay products and are a marker of cerebral microangiopathy, most often lipohyalinosis. They are frequently observed in ischemic neurovascular disease, especially lacunar and hemorrhagic. They may thus have prognostic value. Microbleeds are often present in dementia, especially vascular dementia. The therapeutic consequences of the discovery of microbleeds remain very uncertain, especially in terms of the use of antithrombotic agents.",*Cerebral Hemorrhage/complications/diagnosis/etiology;Humans;Magnetic Resonance Imaging;Microvessels;Risk Factors,"Goas, P.;Timsit, S.",2010,Jun,10.1016/j.lpm.2009.07.026,0,
4201,An image processing framework for white matter segmentation in suspected Alzheimer’s disease,"White Matter (WM) atrophy is a good marker of cognitive decline and progression of Alzheimer’s disease (AD). Precise segmentation of WM from structural Magnetic Resonance (MR) images is pivotal in the accurate quantification of WM atrophy. An image processing framework for the accurate segmentation of WM is proposed in this article. The proposed framework comprises background removal, restoration of the image with Non-Local Means (NLM) Filter, enhancement with Contrast Limited Adaptive Histogram Equalization (CLAHE), skull stripping and k-Means segmentation with histogram guided initialization. The framework exhibited a mean Dice Similarity Index (DSI) of 87.27% with a standard deviation of ± 5.74, on axial plane MR images of T1 series, from 30 subjects, against manual segmentation as ground truth.",aged;Alzheimer disease;article;brain atrophy;clinical article;cognitive defect;controlled study;diagnostic imaging;female;histogram;human;image analysis;image processing;image segmentation;limit of quantitation;male;nuclear magnetic resonance imaging;white matter,"Gnana Jebadas, D.;Albert Raj, A.",2017,,,0,
4202,Brain MRI markers and dropout in a longitudinal study of cognitive aging: the Three-City Dijon Study,"OBJECTIVE: Longitudinal studies of dementia rely on the assumption that individuals who drop out are comparable to those who remain in the study, adjusting for measured covariates. Existing methods to handle dropouts account for differences based on past health and cognitive measures. We assess whether such adjustments fully account for differences in future dementia risk. METHODS: Among Three-City Study participants in Dijon, France, with 1 (n = 1,633) or 2 (n = 1,168) brain MRI scans, we tested whether white matter lesion volume (WMLV), hippocampal volume, or brain CSF volume predicted dropout (""unable to contact"" or ""refused interview"") in repeated-measures logistic regression with up to 4 follow-ups (average 3.5 waves). Using linear regression, we also estimated differences in MRI volumes and MRI changes by subsequent dropout status and estimated plausible ranges for selective attrition bias based on these associations. Models were adjusted for demographic, health, and cognitive score covariates. RESULTS: Baseline greater WMLV predicted increased odds of dropping out (adjusted odds ratio = 1.71; 95% confidence interval [CI] 1.20-2.43). Among participants with 2 MRI scans, individuals who subsequently dropped out had significantly worse declines in hippocampal volume (-0.30 SD difference; 95% CI -0.43 to -0.17) between the first and second MRI scans. CONCLUSIONS: Higher future dementia risk, indicated by worse past brain MRI findings, predicted future study dropout. Adjustment for selective attrition, based on MRI markers when available, may help reduce bias in estimates of dementia incidence and improve research on dementia risk factors. MRI findings may also help prospectively identify cohort members at elevated risk of attrition.","Aged;Aging/*physiology;Biomarkers/cerebrospinal fluid;Brain/*metabolism/*pathology/physiopathology;Cognition Disorders/epidemiology/*metabolism;Dementia/diagnosis/epidemiology/pathology;Female;France/epidemiology;Humans;Interview, Psychological;Leukoencephalopathies/epidemiology/metabolism/pathology;Longitudinal Studies;Magnetic Resonance Imaging/*methods;Male;Neuropsychological Tests;*Patient Dropouts;Predictive Value of Tests;Prospective Studies","Glymour, M. M.;Chene, G.;Tzourio, C.;Dufouil, C.",2012,Sep 25,10.1212/WNL.0b013e31826cd62a,0,
4203,Familial arteriopathic leukoencephalopathy: Imaging and neuropathologic findings,"We present the clinical, imaging, and neuropathologic data for a family with an autosomal dominant, nonhypertensive, progressive cerebral arteriopathy and leukoencephalopathy. Clinical presentation was characterized by progressive dementia, gait abnormalities, and, in some, Parkinson-like symptoms. MR abnormalities, consisting of white matter T2 hyperintensities and cystic-appearing T1 hypointensities, were present in seven family members. The basal ganglia also showed cystic abnormalities. Neuropathologic examination in two cases revealed numerous lacunar infarctlike lesions, extensive demyelination, and widespread hyalinization of arteriolar walls with karyolysis and granular deposits within the media. These findings appear to constitute further evidence of a genetically determined arteriopathic leukoencephalopathy.",,"Glusker, P.;Horoupian, D. S.;Lane, B.",1998,March,,0,
4204,Reduced glucose uptake and Abeta in brain regions with hyperintensities in connected white matter,"Interstitial concentration of amyloid beta (Ass) is positively related to synaptic activity in animal experiments. In humans, Ass deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Ass accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 +/- 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Ass was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (beta = 0.045) and FDG-PET (beta = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Ass deposition.",Aged;Amyloid beta-Peptides/ metabolism;Aniline Compounds;Blood Glucose/ metabolism;Brain/ metabolism/pathology;Female;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography;Thiazoles;White Matter/ metabolism/pathology,"Glodzik, L.;Kuceyeski, A.;Rusinek, H.;Tsui, W.;Mosconi, L.;Li, Y.;Osorio, R. S.;Williams, S.;Randall, C.;Spector, N.;McHugh, P.;Murray, J.;Pirraglia, E.;Vallabhajosula, S.;Raj, A.;de Leon, M. J.",2014,Oct 15,10.1016/j.neuroimage.2014.06.060,0,
4205,Cerebrospinal immunoglobulin level changes and clinical response to treatment of Hashimoto?s encephalopathy,"We describe a 64-year-old male who presented with a 2-year history of behavioral and cognitive decline. Brain imaging showed nonenhancing hemispheric white matter lesions. Blood work revealed elevated thyroglobulin and thyroperoxidase antibody levels. Cerebrospinal fluid (CSF) analysis was largely negative, except for an elevated protein and immunoglobulin G (IgG) level. Because of the absence of stroke, central nervous system (CNS) tumor, or infection, this patient fits into criteria of Hashimoto?s encephalopathy. His Mini-Mental State Examination score improved from 10 to 29 after initial immunotherapy. The patient remained stable over 6 months with monthly outpatient total plasma exchange, but symptoms recurred within 3 months when the outpatient therapy was discontinued. A follow-up CSF IgG level was found to be increased and the treatment was repeated with partial clinical improvement and decline in CSF IgG level. He then underwent high dose steroid treatment after which patients? clinical condition stabilized and CSF analysis showed even further IgG decline.",,"Gliebus, G.;Lippa, C. F.",2009,October,,0,
4206,Whole brain white matter histogram analysis of diffusion tensor imaging data detects microstructural damage in mild cognitive impairment and alzheimer's disease patients,"BACKGROUND: Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need. PURPOSE: To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS). STUDY TYPE: Prospective. POPULATION/SUBJECTS: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS). FIELD STRENGTH: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI). ASSESSMENT: Normal-appearing white matter (NAWM) masks were obtained using the T1 -weighted volumes for tissue segmentation and T2 -weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset. STATISTICAL TESTS: One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis. RESULTS: For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for ""HS vs. patients"" comparison and 0.74 for ""AD vs. others"" comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC of 0.75 for ""HS vs. patients"" comparison and 0.75 for ""AD vs. others"" comparison. DATA CONCLUSION: AXD of NAWM might be an early marker of microstructural brain tissue changes occurring during the AD course and might be useful for assessing disease progression. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.",Alzheimer's disease;cognitive dysfunction;diffusion tensor imaging;magnetic resonance imaging;white matter,"Giulietti, G.;Torso, M.;Serra, L.;Spano, B.;Marra, C.;Caltagirone, C.;Cercignani, M.;Bozzali, M.;Alzheimer's Disease Neuroimaging, Initiative",2018,Jan 21,,0,
4207,Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different,"In order to clarify the coagulation profile accompanying ischemic stroke, which may have implications on therapeutic strategies, we performed a prospective study to evaluate the hemostatic parameters in the first 24 h after the onset of cortical atherothrombotic infarct and lacunar infarction. Twenty-seven patients with cortical atherothrombotic infarction and 27 patients with lacunar infarction, diagnosed on clinical and CT-scan criteria, had blood samples taken within the first 24 h after onset of the stroke, and before anticoagulant treatment had been started. Levels of fibrinogen, von Willebrand factor, D-dimers, prothrombin factors 1 + 2, anti-thrombin III, and C-protein and S-proteins, were measured. Laboratory tests detected the following abnormalities: a protein C deficiency was observed in 1 case of cortical infarction and in 1 case of lacunar infarction; a decrease in S-protein was observed in 1 case of cortical infarction, and the presence of lupus anticoagulant in 4 cases (2 in cortical and 2 in lacunar infarction). Various degrees of coagulation activation were observed. Statistically significant activation of the coagulation was observed in the patients with cortical infarction, compared to normal patients adjusted for age: the levels of DDI were significantly raised (2298 +/- 2221 ng ml-1 vs. 750 +/- 400 ng ml-1) (p < 0.03) as were F1 + 2 levels (3.9 +/- 2.8 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1). (p < 0.01). In the lacunar infarction group, there was a significant rise in F1 + 2 compared with normal patients adjusted for age (2.2 +/- 1.7 nmol l-1 vs. 1.5 +/- 0.9 nmol l-1) (p < 0.01), while the DDI level was in the normal range, when age was taken into account. In the cortical infarction group, we observed a significantly raised fibrinogen level (4.8 +/- 1.7 g l-1 vs. 3.7 +/- 1.0 g l-1) (p < 0.05) and von Willebrand factor level (271 +/- 104% vs. 178 +/- 103%) (p < 0.01) compared to the lacunar infarction group. In addition, we observed a significantly low level of S-protein in the cortical infarction group (105 +/- 29%) compared to the lacunar infarction group (127 +/- 28%) (p < 0.01). Confirmation of the role of enhanced thrombin activity in the pathogenesis of acute stroke may be an important determinant in its therapeutic management.","Aged;Aged, 80 and over;Blood Coagulation Tests;Brain Ischemia/*etiology;Cerebral Infarction/*etiology;Cerebrovascular Disorders/classification/*etiology;Dementia, Multi-Infarct/*etiology;Female;Hemostasis;Humans;Male;Middle Aged;Prospective Studies;Thrombosis/*complications","Giroud, M.;Dutrillaux, F.;Lemesle, M.;Volot, F.;Lorenzini, J. L.;Becker, F.;Dumas, R.",1998,Jan,,0,
4208,Unsupervised quantitative assessment of Beta amyloid images using Florbetaben(18F),"Background Amyloid PET imaging is used to detect brain amyloid accumulation which is considered a key event in the onset of Alzheimer's disease. There are no standard methods for unsupervised assessment of tracer binding. Brain segmentation procedures are limited by poor signal differences between gray (GM) and white matter (WM). This work is aimed to propose an automated method for brain tissues segmentation and unsupervised quantification of brain amyloid binding. Methods Subjects were recruited within a prospective study (EudraCT number: 2015- 001184-39) at Neurology Unit of S. Andrea Hospital and Memory Laboratory CNS-ONLUS of La Spezia. Subjects underwent a neuropsychological battery for assessing different cognitive domains, executive functions and attentional systems. So far a population of 11 patients was enrolled in the study (Age 74+/-10; MMSE, 25+/-6) . PET images were acquired in 3D mode 90 to 110 minutes after intravenous injection of 300 MBq of Florbetaben(18F) (NeuraceqTM) on a DISCOVERY TM 710 PET/CT scanner (GE Medical Systems, Milwaukee, WI). PET scans were converted to standardized uptake values (SUV) and normalized into MNI space using SPM8 T1 template (http://www.fil.ion.ucl.ac.uk/spm/software/ SPM8). Image analysis procedure was implemented under Matlab 7.14 (Math Works Inc., Sherborn, MA). PET images were evaluated by two trained independent readers who were blinded to the clinical results. Whole brain analysis resulted in a scores condensed into a binary interpretation of 0,1 for negative and positive scan respectively. Amyloid PET images were segmented by using hybrid segmentation technique incorporating apriori brain tissues probability distribution and gradient-based approach. GM and WM segmented tissues were used for extracting regional mean SUV values. Data extracted from each patient were grouped according to visual rating results. One-Way analysis was used to test group differences. The linear dependence of SUVs values on MMSE and age was determined by a simple regression. A significance level of p<0.05 was chosen. Results Visual rating of PET images led to the diagnosis of 6 positive and 5 negative subjects. WM-to-GMratio was 1.1+/-0.09 and 1.3+/-0.03 in positive and negative patients respectively (Anova, F=7.1, P=0.025). We found a significant correlation between GM-SUVs and MMSE (R=0.52; P=0.01) in contrast WM-SUVs did not show significant correlation on MMSE. We found positive correlation between WM-to-GM SUVs ratio withMMSE (R=0.73, P=0.0008), whereas no correlation of GMand WMSUVs on age was found. Conclusion Our findings suggest that unsupervised quantitative assessment of PET amyloid binding may be useful to improve diagnosis and predict disease progression in Alzheimer's disease.",aged;Alzheimer disease;analysis of variance;brain analysis;chemical binding;clinical article;clinical trial;controlled clinical trial;controlled study;data analysis software;diagnosis;disease course;executive function;hospital;human;human tissue;human versus animal comparison;image analysis;intravenous drug administration;memory;Mini Mental State Examination;neurology;nonhuman;PET-CT scanner;positron emission tomography;probability;prospective study;quantitative study;single blind procedure;white matter;amyloid beta protein;endogenous compound;florbetaben;ion,"Giovannini, E.;Riondato, M.;Leoncini, R.;Passera, C.;Carabelli, E.;Ferrando, O.;Tartaglione, A.;Mannironi, A.;Ciarmiello, A.",2017,,,0,
4209,Syntactic comprehension deficits are associated with MRI white matter alterations in dementia,"Comprehension difficulties associated with periventricular and deep white matter alterations (WMA) in mild dementia were investigated using portions of the Boston Diagnostic Aphasia Examination (BDAE) Complex Ideation subtest and Syntax subtests. Mild dementia participants were grouped according to the extent of their WMA as observed on magnetic resonance imaging (mild WMA n = 45 vs. moderate to severe WMA n = 52). Correlation and regression analyses also were performed to examine the link between WMA and comprehension abilities, as well as the link between comprehension abilities and neuropsychological measures of executive functioning, language, episodic memory, and overall dementia severity. Results showed that the WMA groups differed on the BDAE-Syntax subtests, with the severe WMA group demonstrating more impairment. Correlation and regression analyses including the entire sample also demonstrated that the extent of WMA was significantly linked to Syntax test scores but not Complex Ideation scores. Regression analyses including neuropsychological measures showed that the BDAE-Complex Ideation score was marginally predicted by only overall dementia severity, whereas the BDAE-Syntax scores were significantly predicted by independent measures of working memory/executive functioning. In conclusion, greater subcortical WMA and executive deficits are associated with greater difficulties in syntactic comprehension in individuals with mild dementia.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/psychology;Brain/ pathology;Cerebral Ventricles/pathology;Comprehension/ physiology;Dementia, Vascular/ diagnosis/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Memory, Short-Term/physiology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests/ statistics & numerical data;Psychometrics;Reading;Semantics;Speech Perception/physiology","Giovannetti, T.;Hopkins, M. W.;Crawford, J.;Bettcher, B. M.;Schmidt, K. S.;Libon, D. J.",2008,Jul,10.1017/s1355617708080715,0,
4210,Kufs disease presenting as a leukoencephalopathy,"We report a case of adult neuronal ceroid lipofuscinosis (Kufs' disease) with leukoencephalopathy on cerebral scan CT and MRI. A 52 year-old woman presented with partial complex epileptic seizure followed by progressive dementia, cerebellar ataxia, pyramidal and akineto-rigid signs and symptoms. After 6 years of evolution, cerebral stereotactic biopsies showed a diffuse gliosis of the white matter, but no clear demyelination. Nerve and glial cells contained numerous PAS + autofluorescent granules. In the oligodendrocytes and astrocytes of the white matter these granules appeared electronmicroscopically as cytoplasmic osmiophilic lamellar bodies with fingerprint profile combined with some curvilinear and rectilinear aspects. The cortical nerve cells contained granular osmiophilic bodies. This 'leukoencephalopathic' variant of Kufs' disease is probably related to the pigmentary type of orthochromatic leukodystrophy, wherein similar inclusions have been only described in the macrophages and glial cells of the white matter.",adult;article;case report;computer assisted tomography;dementia;female;glia cell;human;human tissue;leukoencephalopathy;nuclear magnetic resonance,"Gille, M.;Brucher, J. M.;Indekeu, P.;Bisteau, M.;Kollmann, P.",1995,,,0,
4211,Cerebral infarction in patients with AIDS,"PURPOSE: To establish the frequency, distribution, and pathogenesis of cerebral infarction as confirmed with MR imaging in a cohort of patients with acquired immunodeficiency syndrome (AIDS). METHODS: We reviewed all (71) abnormal cranial MR studies obtained at our institution in human immunodeficiency virus (HIV)-positive patients over a 2-year period and recorded the number and distribution of ischemic lesions, any associated abnormalities, and the MR angiographic findings, where available. Patients' charts were studied for relevant clinical data, biochemical and culture results, and potential etiologic factors. RESULTS: Twenty-two infarcts were seen in 13 of the 71 patients. Of these 22, the basal ganglia area was affected in 15, the middle cerebral artery territory in two, and the vertebrobasilar territory in five. Five patients had concomitant evidence of infection, six others used cocaine or were intravenous drug abusers. MR angiography was performed in eight patients; two of these had multiple lesions consistent with vasculitis, two had isolated lesions that corresponded with their parenchymal infarct, and four had normal findings. CONCLUSIONS: The frequency of infarction was 18%, higher than previously reported. The pathogenesis of infarction was multifactorial. Underlying infectious causes were identified in 39% of patients. Two patients had an idiopathic vasculitis.",AIDS Dementia Complex/ diagnosis/pathology;AIDS-Related Opportunistic Infections/ diagnosis/pathology;Adult;Brain/pathology;Brain Diseases/ diagnosis/pathology;Cerebral Infarction/ diagnosis/pathology;Cohort Studies;Female;HIV Seropositivity/ diagnosis/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged,"Gillams, A. R.;Allen, E.;Hrieb, K.;Venna, N.;Craven, D.;Carter, A. P.",1997,Sep,,0,
4212,Atypical tauopathy with massive involvement of the white matter,,Brain/*pathology;Brain Diseases/metabolism/*pathology;Cerebral Cortex/pathology;Dementia/pathology;Humans;Magnetic Resonance Imaging;Neurons/pathology;Tauopathies/*pathology;tau Proteins/metabolism,"Giaccone, G.;Marcon, G.;Mangieri, M.;Morbin, M.;Rossi, G.;Fetoni, V.;Patriarca, C.;Catania, M.;Di Fede, G.;Tagliavini, F.;Merlin, M.",2008,Aug,10.1111/j.1365-2990.2007.00927.x,0,
4213,Multiple sclerosis exploration based on automatic MRI modalities segmentation approach with advanced volumetric evaluations for essential feature extraction,"Multiple Sclerosis (MS) could be considered as one of the most serious neurological diseases that can cause damage to the central nervous system. Such pathology has increased dramatically during the past few years. Hence, MS exploration has captivated the interest of various research studies in clinical as well as technological fields such as medical imaging. In this context, this paper introduced a new MS exploration approach based on cerebral segmentation and MS lesion identification using the fusion of magnetic resonance (MRI) modalities sequences. The proposed segmentation approach is based on extracted volumetric features that could be deduced from the gray-level co-occurrence matrix (GLCM) and the gray-level run length (GLRLM) matrix. Volumetric features extraction would be performed by using new voxel wise techniques while preserving connectivity, spatial and shape information. In addition, our segmentation approach includes an optimized feature selection process combining the genetic algorithm (GA) and the support vector machine (SVM) tool in order to preserve only the essential features that could distinguish the main brain tissues and the MS lesions within both white matter and gray matter. The evaluation was carried out on four clinical databases. The results revealed an acceptable conformity with the ground truths compared to those of the usual methods Besides, our approach has proved its ability to select the most discriminative features, ensuring an acceptable cerebral segmentation (averages: Dice = 0.62 ± 0.11, true positive rate ‘TPR’ = 0.64 ± 0.12 and positive predictive value ‘PPV’ = 0.64 ± 0.14) and MS lesions identification with an acceptable accuracy rate (averages: Dice = 0.66 ± 0.07, TPR = 0.70 ± 0.12 and PPV = 0.67 ± 0.03). Based on these promising results, a computer aided diagnosis (CAD) system was henceforth conceived and could be useful for clinicians in order to carefully facilitate MS exploration. Such a helpful CAD system was really highly needed for clinical explorations and could be extended to other neurological pathologies such as Alzheimer's and Parkinson's diseases.",article;brain tissue;computer aided design;diagnostic accuracy;extraction;genetic algorithm;gray matter;human;human tissue;image segmentation;multiple sclerosis;neuroimaging;nuclear magnetic resonance imaging;predictive value;priority journal;support vector machine;volumetry;white matter,"Ghribi, O.;Sellami, L.;Slima, M. B.;Mhiri, C.;Dammak, M.;Hamida, A. B.",2018,,10.1016/j.bspc.2017.07.008,0,
4214,Callosal dementia: Behavioral disorders related to centro and extrapontine myelinolysis,"We report the behavioral symptoms presented by a 57-year-old man as the first sign of a Marchiafava-Bignami syndrome and by a 44-year-old woman with centro and extrapontine myelinolysis. These observations define a clinical entity, that we named callosal dementia characterized by: 5) fronto-limbic signs with coarse interjections, repetitive and antisocial behavior, alternation of lack of incitation and agitation; 6) elements of a Balint syndrome (suggestive of a posterior callosal involvement), with a pseudo- hallucinated look and a gaze apraxia; 7) signs of callosal disconnection and; signs of adjacent white matter involvement, with paucity of vocal and facial expression modulation: Early recognition of these features of callosal dementia may be very helpful for diagnosis of suspected myelinolysis, leading to a more careful research of clinical signs of callosal disconnection and prompting neuroimaging with MRI. A rapid confirmation of the diagnosis may prevent progression to centro or extrapontine myelinolysis, that may sometimes still be lethal, by adequate supportive measures (slow correction of electrolytes imbalance, correction of deficiencies, total alcohol withdrawal).",adult;agitation;alcohol withdrawal;antisocial behavior;apraxia;article;case report;central pontine myelinolysis;compulsion;corpus callosum;dementia;electrolyte disturbance;female;frontal lobe;gaze;human;limbic system;male;nuclear magnetic resonance imaging;syndrome;white matter,"Ghika-Schmid, F.;Ghika, J.;Assal, G.;Bogousslavsky, J.",1999,,,0,
4215,Presymptomatic hypertension is a major feature in the diagnosis of progressive supranuclear palsy,"OBJECTIVE: To examine the history of hypertension (HT) in patients with parkinsonism (PS) of various causes. PATIENTS: Nine hundred twenty-three patients with PS listed in a citywide movement disorders registry. Hypertension was defined as blood pressure above 150/90 mm Hg on at least 2 occasions or a history of antihypertensive medication use. RESULTS: Overall, 184 patients (20.6%) had a history of HT. Fifty-three (16.6%) of 320 patients with levodopa-responsive parkinsonism (PD) had a history of HT; similar prevalence of presymptomatic HT was seen for PS and dementia (22/165 [13.3%]), including probable diffuse Lewy body disease and multiple system atrophy of the nigrostriatal degenerative type (33/171 [19.3%]). Olivopontocerebellar atrophy (7/40 [18%]), corticobasal ganglionic degeneration (5/15 [33.3%]), drug-induced PS (9/38 [23.1%]), and the predominantly tremulous forms of Parkinson disease (17/43 [39.5%]) showed a higher prevalence of HT. Patients with familial PS (n = 36), early-onset PD (n = 14), multiple system atrophy of the Shy-Drager type (n = 11), and postencephalitic PS (n = 6) had no history of HT. In 100 patients with PS of various rare etiologies, a history of HT was seen in less than 5%. The highest prevalence of HT was seen in patients with clinically diagnosed progressive supranuclear palsy (n = 42), of whom 34 (81.0%) had a history of HT. CONCLUSIONS: A presymptomatic history of HT is a major feature in the clinical history of progressive supranuclear palsy and may be a diagnostic criterion. Its significance is unknown, but adrenergic nuclei of the brainstem are severely affected, and HT may be the first symptom arising from involvement of these nuclei. This could also explain the features of small vessel disease seen on computed tomography or magnetic resonance imaging in 50% of our patients, as in previous reports.","Adult;Aged;Brain Diseases/complications;Female;Humans;Hypertension/ diagnosis/epidemiology/ etiology;Male;Middle Aged;Parkinson Disease, Secondary/ complications;Prevalence;Supranuclear Palsy, Progressive/ complications/ diagnosis","Ghika, J.;Bogousslavsky, J.",1997,Sep,,0,
4216,Progress in hereditary tauopathies: a mutation in the Tau gene (G389R) causes a Pick disease-like syndrome,"We describe the clinical and pathologic phenotypes of the G389R mutation in exon 13 of the Tau gene. Progressive aphasia and memory disturbance are the initial signs and begin in the fourth or fifth decade of life, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs and dementia. Death occurs after two to five years. Magnetic resonance imaging and neuropathologic studies show frontal and temporal atrophy. Pick body-like and axonal filamentous inclusions found in the neocortex and subcortical white matter, respectively, are tau immunoreactive. Immunoblot analysis of sarkosyl-insoluble tau shows two major bands of 60 and 64 kDa that, upon dephosphorylation, resolve into four bands of three- and four-repeat isoforms. Isolated tau filaments are often straight and occasionally twisted. Recombinant mutant tau protein shows a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. The present findings indicate that the G389R mutation in Tau can cause a dementia similar to that in Pick's disease.","Adult;Amino Acid Substitution;Atrophy;Brain/pathology/ultrastructure;Dementia/ genetics/pathology/psychology;Frontal Lobe/pathology;Humans;Italy;Mutation, Missense;Phenotype;Pick Disease of the Brain/ genetics/pathology/psychology;Syndrome;Temporal Lobe/pathology;tau Proteins/ genetics","Ghetti, B.;Murrell, J. R.;Zolo, P.;Spillantini, M. G.;Goedert, M.",2000,,,0,
4217,Cerebral microbleeds (CMBs) - relevance for mechanisms of cerebral hemorrhage--analysis of 24 MRI evaluated patients,"INTRODUCTION: The new MRI techniques introduced in the last decade allowed the detection of cerebral microbleeds (CMBs) in different groups of diseases: stroke, Alzheimer disease, vascular dementia or healthy people of advanced age. CMBs are radiologically defined as small, rounded, homogeneous, hypointense lesions on T2*-weighed gradient-recalled echo (T2*-GRE) sequences. OBJECTIVE AND METHOD: We evaluated the prevalence, number and location of CBMs in a cohort of 26 consecutive cerebral hemorrhage patients admitted in the National Institute of Neurology and Neurovascular Diseases. We also assessed the association between CMB, classical vascular risk factors and small vessel disease. RESULTS AND CONCLUSIONS: From the 26 patients, 2 patients had secondary intracerebral hemorrhage (ICH) (hemorrhage in metastasis, respectively a cavernoma). From the 24 ICH patients 12 have had at least 1 CMB lesion. The average volume of the cerebral hemorrhage was larger in patients with CMBs, with a relative increase of 42%. Small vessel disease was associated with a significant increase in the presence of CMBs (relative increase of 86%). In both cases, however, since the number of patients enrolled was small, the correlations did not reach statistical significance.",Cerebral Hemorrhage/*diagnosis/*pathology;Female;Humans;Magnetic Resonance Imaging/*methods;Male;CMBs;cerebral microbleeds;intracerebral hemorrhage;small vessel disease,"Ghelmez, D.;Sorin Tuta, S.;Popa, C.",2013,,,0,
4218,Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology,"Traumatic brain injury can lead to the neurodegenerative disease chronic traumatic encephalopathy. This condition has a clear neuropathological definition but the relationship between the initial head impact and the pattern of progressive brain pathology is poorly understood. We test the hypothesis that mechanical strain and strain rate are greatest in sulci, where neuropathology is prominently seen in chronic traumatic encephalopathy, and whether human neuroimaging observations converge with computational predictions. Three distinct types of injury were simulated. Chronic traumatic encephalopathy can occur after sporting injuries, so we studied a helmet-to-helmet impact in an American football game. In addition, we investigated an occipital head impact due to a fall from ground level and a helmeted head impact in a road traffic accident involving a motorcycle and a car. A high fidelity 3D computational model of brain injury biomechanics was developed and the contours of strain and strain rate at the grey matter-white matter boundary were mapped. Diffusion tensor imaging abnormalities in a cohort of 97 traumatic brain injury patients were also mapped at the grey matter-white matter boundary. Fifty-one healthy subjects served as controls. The computational models predicted large strain most prominent at the depths of sulci. The volume fraction of sulcal regions exceeding brain injury thresholds were significantly larger than that of gyral regions. Strain and strain rates were highest for the road traffic accident and sporting injury. Strain was greater in the sulci for all injury types, but strain rate was greater only in the road traffic and sporting injuries. Diffusion tensor imaging showed converging imaging abnormalities within sulcal regions with a significant decrease in fractional anisotropy in the patient group compared to controls within the sulci. Our results show that brain tissue deformation induced by head impact loading is greatest in sulcal locations, where pathology in cases of chronic traumatic encephalopathy is observed. In addition, the nature of initial head loading can have a significant influence on the magnitude and pattern of injury. Clarifying this relationship is key to understanding the long-term effects of head impacts and improving protective strategies, such as helmet design.",adult;article;biomechanics;brain mapping;brain size;brain tissue;chronic traumatic encephalopathy;cohort analysis;controlled study;diffusion tensor imaging;female;football;fractional anisotropy;gray matter;helmet;human;major clinical study;male;model;neuroimaging;neuropathology;occipital lobe;prediction;predictive value;priority journal;simulation;tauopathy;three dimensional imaging;traffic accident;traumatic brain injury;white matter,"Ghajari, M.;Hellyer, P. J.;Sharp, D. J.",2017,,10.1093/brain/aww317,0,
4219,Automated detection of white matter hyperintensities of all sizes in cerebral small vessel disease,"PURPOSE: White matter hyperintensities (WMH) are seen on FLAIR-MRI in several neurological disorders, including multiple sclerosis, dementia, Parkinsonism, stroke and cerebral small vessel disease (SVD). WMHs are often used as biomarkers for prognosis or disease progression in these diseases, and additionally longitudinal quantification of WMHs is used to evaluate therapeutic strategies. Human readers show considerable disagreement and inconsistency on detection of small lesions. A multitude of automated detection algorithms for WMHs exists, but since most of the current automated approaches are tuned to optimize segmentation performance according to Jaccard or Dice scores, smaller WMHs often go undetected in these approaches. In this paper, the authors propose a method to accurately detect all WMHs, large as well as small. METHODS: A two-stage learning approach was used to discriminate WMHs from normal brain tissue. Since small and larger WMHs have quite a different appearance, the authors have trained two probabilistic classifiers: one for the small WMHs (3 mm effective diameter) and one for the larger WMHs (>3 mm in-plane effective diameter). For each size-specific classifier, an Adaboost is trained for five iterations, with random forests as the basic classifier. The feature sets consist of 22 features including intensities, location information, blob detectors, and second order derivatives. The outcomes of the two first-stage classifiers were combined into a single WMH likelihood by a second-stage classifier. Their method was trained and evaluated on a dataset with MRI scans of 362 SVD patients (312 subjects for training and validation annotated by one and 50 for testing annotated by two trained raters). To analyze performance on the separate test set, the authors performed a free-response receiving operating characteristic (FROC) analysis, instead of using segmentation based methods that tend to ignore the contribution of small WMHs. RESULTS: Experimental results based on FROC analysis demonstrated a close performance of the proposed computer aided detection (CAD) system to human readers. While an independent reader had 0.78 sensitivity with 28 false positives per volume on average, their proposed CAD system reaches a sensitivity of 0.73 with the same number of false positives. CONCLUSIONS: The authors have developed a CAD system with all its ingredients being optimized for a better detection of WMHs of all size, which shows performance close to an independent reader.","Automation;Cerebral Small Vessel Diseases/ diagnostic imaging;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging;White Matter/ diagnostic imaging","Ghafoorian, M.;Karssemeijer, N.;van Uden, I. W.;de Leeuw, F. E.;Heskes, T.;Marchiori, E.;Platel, B.",2016,Dec,,0,
4220,Deep multi-scale location-aware 3D convolutional neural networks for automated detection of lacunes of presumed vascular origin,"Lacunes of presumed vascular origin (lacunes) are associated with an increased risk of stroke, gait impairment, and dementia and are a primary imaging feature of the small vessel disease. Quantification of lacunes may be of great importance to elucidate the mechanisms behind neuro-degenerative disorders and is recommended as part of study standards for small vessel disease research. However, due to the different appearance of lacunes in various brain regions and the existence of other similar-looking structures, such as perivascular spaces, manual annotation is a difficult, elaborative and subjective task, which can potentially be greatly improved by reliable and consistent computer-aided detection (CAD) routines. In this paper, we propose an automated two-stage method using deep convolutional neural networks (CNN). We show that this method has good performance and can considerably benefit readers. We first use a fully convolutional neural network to detect initial candidates. In the second step, we employ a 3D CNN as a false positive reduction tool. As the location information is important to the analysis of candidate structures, we further equip the network with contextual information using multi-scale analysis and integration of explicit location features. We trained, validated and tested our networks on a large dataset of 1075 cases obtained from two different studies. Subsequently, we conducted an observer study with four trained observers and compared our method with them using a free-response operating characteristic analysis. Shown on a test set of 111 cases, the resulting CAD system exhibits performance similar to the trained human observers and achieves a sensitivity of 0.974 with 0.13 false positives per slice. A feasibility study also showed that a trained human observer would considerably benefit once aided by the CAD system.",Automated detection;Convolutional neural networks;Deep learning;Lacunes;Location-aware;Multi-scale,"Ghafoorian, M.;Karssemeijer, N.;Heskes, T.;Bergkamp, M.;Wissink, J.;Obels, J.;Keizer, K.;Leeuw, F. E.;Ginneken, B. V.;Marchiori, E.;Platel, B.",2017,,,0,
4221,APOE ε 2 is associated with white matter hyperintensity volume in CADASIL,"Apolipoprotein E (APOE) increases the risk for Alzheimer's disease (ε 4 allele) and cerebral amyloid angiopathy (ε 2 and ε 4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium. Compared with APOE ε 3/ε 3, WMHV was increased in APOE ε 2 (P = 0.02) but not APOE ε 4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE ε 2 on WMHV caused by pure SVD.",apolipoprotein E2;apolipoprotein E3;Notch3 receptor;adult;allele;article;brain size;CADASIL;controlled study;diabetes mellitus;female;gene mutation;genetic association;genotype;good clinical practice;human;hypercholesterolemia;hypertension;major clinical study;male;multicenter study;nuclear magnetic resonance imaging;priority journal;risk factor;white matter;white matter hyperintensity volume,"Gesierich, B.;Opherk, C.;Rosand, J.;Gonik, M.;Malik, R.;Jouvent, E.;Hervé, D.;Adib-Samii, P.;Bevan, S.;Pianese, L.;Silvestri, S.;Dotti, M. T.;De Stefano, N.;Van Der Grond, J.;Boon, E. M. J.;Pescini, F.;Rost, N.;Pantoni, L.;Lesnik Oberstein, S. A.;Federico, A.;Ragno, M.;Markus, H. S.;Tournier-Lasserve, E.;Chabriat, H.;Dichgans, M.;Duering, M.;Ewers, M.",2016,,,0,
4222,APOE varepsilon2 is associated with white matter hyperintensity volume in CADASIL,"Apolipoprotein E (APOE) increases the risk for Alzheimer's disease (varepsilon4 allele) and cerebral amyloid angiopathy (varepsilon2 and varepsilon4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium. Compared with APOE varepsilon3/varepsilon3, WMHV was increased in APOE varepsilon2 (P = 0.02) but not APOE varepsilon4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE varepsilon2 on WMHV caused by pure SVD.","Adult;*Alleles;Apolipoprotein E2/genetics/*metabolism;CADASIL/genetics/*metabolism/pathology;Female;Gene Frequency/genetics;Genome-Wide Association Study;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Polymorphism, Single Nucleotide;Protein Isoforms;Regression Analysis;Risk Factors;White Matter/*pathology","Gesierich, B.;Opherk, C.;Rosand, J.;Gonik, M.;Malik, R.;Jouvent, E.;Herve, D.;Adib-Samii, P.;Bevan, S.;Pianese, L.;Silvestri, S.;Dotti, M. T.;De Stefano, N.;van der Grond, J.;Boon, E. M.;Pescini, F.;Rost, N.;Pantoni, L.;Oberstein, S. A.;Federico, A.;Ragno, M.;Markus, H. S.;Tournier-Lasserve, E.;Chabriat, H.;Dichgans, M.;Duering, M.;Ewers, M.",2016,Jan,10.1038/jcbfm.2015.85,0,
4223,Features and Determinants of Lacune Shape: Relationship With Fiber Tracts and Perforating Arteries,"Background and Purpose - Lacunes are a major manifestation of cerebral small vessel disease. Although still debated, the morphological features of lacunes may offer mechanistic insights. We systematically analyzed the shape of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetically defined small vessel disease. Methods - A total of 88 incident lacunes from 57 patients were segmented from 3-dimensional T1 magnetic resonance images and 3 dimensionally reconstructed. Anatomic location, diameter, volume, surface area, and compactness of lacunes were assessed. The shape was analyzed using a size, orientation, and position invariant spectral shape descriptor. We further investigated the relationship with perforating arteries and fiber tracts. Results - Lacunes were most abundant in the centrum semiovale and the basal ganglia. Diameter, volume, and surface area of lacunes in the basal ganglia and centrum semiovale were larger than in other brain regions. The spectral shape descriptor revealed a continuum of shapes with no evidence for distinct classes of lacunes. Shapes varied mostly in elongation and planarity. The main axis and plane of lacunes were found to align with the orientation of perforating arteries but not with fiber tracts. Conclusions - Elongation and planarity are the primary shape principles of lacunes. Their main axis and plane align with perforating arteries. Our findings add to current concepts on the mechanisms of lacunes.",adult;aged;artery perforation;article;basal ganglion;brain size;CADASIL;female;human;image analysis;lacune;major clinical study;male;nerve fiber;neurologic disease;nuclear magnetic resonance imaging;priority journal;prospective study;surface area;three dimensional imaging,"Gesierich, B.;Duchesnay, E.;Jouvent, E.;Chabriat, H.;Schmidt, R.;Mangin, J. F.;Duering, M.;Dichgans, M.",2016,,10.1161/strokeaha.116.012779,0,4224
4224,Features and Determinants of Lacune Shape: Relationship With Fiber Tracts and Perforating Arteries,"BACKGROUND AND PURPOSE—: Lacunes are a major manifestation of cerebral small vessel disease. Although still debated, the morphological features of lacunes may offer mechanistic insights. We systematically analyzed the shape of incident lacunes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetically defined small vessel disease. METHODS—: A total of 88 incident lacunes from 57 patients were segmented from 3-dimensional T1 magnetic resonance images and 3 dimensionally reconstructed. Anatomic location, diameter, volume, surface area, and compactness of lacunes were assessed. The shape was analyzed using a size, orientation, and position invariant spectral shape descriptor. We further investigated the relationship with perforating arteries and fiber tracts. RESULTS—: Lacunes were most abundant in the centrum semiovale and the basal ganglia. Diameter, volume, and surface area of lacunes in the basal ganglia and centrum semiovale were larger than in other brain regions. The spectral shape descriptor revealed a continuum of shapes with no evidence for distinct classes of lacunes. Shapes varied mostly in elongation and planarity. The main axis and plane of lacunes were found to align with the orientation of perforating arteries but not with fiber tracts. CONCLUSIONS—: Elongation and planarity are the primary shape principles of lacunes. Their main axis and plane align with perforating arteries. Our findings add to current concepts on the mechanisms of lacunes.",,"Gesierich, B.;Duchesnay, E.;Jouvent, E.;Chabriat, H.;Schmidt, R.;Mangin, J. F.;Duering, M.;Dichgans, M.",2016,,,0,
4225,White Matter Degradation is Associated with Reduced Financial Capacity in Mild Cognitive Impairment and Alzheimer's Disease,"Financial capacity (FC) is a cognitively complex activity of daily living that declines in mild cognitive impairment (MCI) and Alzheimer's disease (AD), limiting an individual's ability to manage one's finances and function independently. The neural underpinnings of this decline in function are poorly understood but likely involve age-related and disease-related degradation across structural networks. The purpose of the current study was to determine if altered white matter integrity is associated with declining FC in persons with MCI and AD compared to older controls. Individuals with MCI due to AD (n = 31), mild dementia (n = 39), and cognitively healthy older adults (n = 60) were administered a neuropsychological battery including the FC Instrument, a performance-based measure of FC. All 130 participants also underwent diffusion tensor imaging (DTI) upon which tract-based spatial statistics were performed. Both FC and white matter integrity decreased in accordance with disease severity with little to no effect in healthy elderly, significant effects in MCI, and greater effects in AD. Regional white matter degradation (increased diffusivities and decreased fractional anisotropy) was associated with reduced FC in both MCI and AD groups even after controlling for age, education, and gender. Specifically, in MCI, decreased fractional anisotropy, but not increased diffusivities, was associated with poorer FC in widespread cingulo-parietal-frontal and temporo-occipital areas. In AD, rather than anisotropy, increased mean and axial diffusivities in anterior cingulate, callosum, and frontal areas associated with poorer FC. These findings suggest a severity gradient of white matter degradation across DTI metrics and AD stages that predict declining financial skill and knowledge.",Aging;Alzheimer's disease;brain;diffusion tensor imaging;financial management;magnetic resonance imaging;mild cognitive impairment;white matter connectivity,"Gerstenecker, A.;Hoagey, D. A.;Marson, D. C.;Kennedy, K. M.",2017,,,0,
4226,Frontotemporoparietal asymmetry and lack of illness awareness in schizophrenia,"Introduction: Lack of illness awareness or anosognosia occurs in both schizophrenia and right hemisphere lesions due to stroke, dementia, and traumatic brain injury. In the latter conditions, anosognosia is thought to arise from unilateral hemispheric dysfunction or interhemispheric disequilibrium, which provides an anatomical model for exploring illness unawareness in other neuropsychiatric disorders, such as schizophrenia. Methods: Both voxel-based morphometry using Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) and a deformation-based morphology analysis of hemispheric asymmetry were performed on 52 treated schizophrenia subjects, exploring the relationship between illness awareness and gray matter volume. Analyses included age, gender, and total intracranial volume as covariates. Results: Hemispheric asymmetry analyses revealed illness unawareness was significantly associated with right < left hemisphere volumes in the anteroinferior temporal lobe (t = 4.83, P = 0.051) using DARTEL, and the dorsolateral prefrontal cortex (t = 5.80, P = 0.003) and parietal lobe (t = 4.3, P = 0.050) using the deformation-based approach. Trend level associations were identified in the right medial prefrontal cortex (t = 4.49, P = 0.127) using DARTEL. Lack of illness awareness was also strongly associated with reduced total white matter volume (r = 0.401, P < 0.01) and illness severity (r = 0.559, P < 0.01). Conclusion: These results suggest a relationship between anosognosia and hemispheric asymmetry in schizophrenia, supporting previous volume-based MRI studies in schizophrenia that found a relationship between illness unawareness and reduced right hemisphere gray matter volume. Functional imaging studies are required to examine the neural mechanisms contributing to these structural observations. © 2012 Wiley Periodicals, Inc.",,"Gerretsen, P.;Chakravarty, M. M.;Mamo, D.;Menon, M.;Pollock, B. G.;Rajji, T. K.;Graff-Guerrero, A.",2013,May,,0,
4227,"Rapidly progressive cognitive impairment, ataxia, and myoclonus: An unusual presentation of a dural arteriovenous fistula","Dural arteriovenous fistulas (DAVFs) have a wide range of clinical presentations, including dementia associated with white matter changes (WMCs). We report a case of DAVF presenting as a rapid progressive dementia and myoclonus without WMCs. A 64-year-old hypertensive and diabetic man was admitted because of a 3-month history of progressive cognitive decline, extrapyramidal and cerebellar signs, and myoclonus. Magnetic resonance imaging (MRI) scans of the brain showed dilated cerebellar veins and T2WI hypersignal in the basal ganglia without WMCs. After admission, he suffered sequential bilateral deep intracerebral hemorrhages. A repeated angioMRI disclosed thrombosis of the distal sagittal and the proximal lateral sinuses. Angiography revealed a torcullar region DAVF. Embolization of the dural fistula was performed. On follow-up, the patients' cognitive deficits improved and myoclonus disappeared. The clinical picture may be explained by venous hypertension in the deep venous system, producing bilateral basal ganglia/thalamic dysfunction and in the posterior fossa. This case shows that DAVFs can produce subcortical dementia without involvement of the deep white matter. © 2012 by National Stroke Association.",,"Geraldes, R.;Albuquerque, L.;Ferro, J. M.;Sousa, R.;Sequeira, P.;Campos, J.",2012,October,,0,
4228,Leukoencephalopathy in normal and pathologic aging: 2. MRI of brain lucencies,"A pilot study was performed to test the ability of MR to evaluate the brain lucencies shown by CT in Alzheimer disease patients and in normal control subjects. Eight patients with presumed Alzheimer disease and 47 normal controls, 12 over the age of 45 years and 35 under age 45, were studied. Each group included subjects with and without CT evidence of leukoencephalopathy. Inversion recovery, saturation recovery, and spin-echo scans were obtained using a 0.3-T permanent magnet prototype unit. Results indicated that MR was more sensitive than CT to parenchymal disease. Seven of the eight patients with Alzheimer disease showed patches of increased signal intensity on SE scans; only three had lucencies on their CT studies. None of the normal subjects under the age of 45 showed periventricular patches of increased SE signal intensity. T2-weighted SE imaging was performed in nine of the 12 normal subjects over 45 years old. Eight of the nine demonstrated periventricular patches of increased SE signal intensity. Faint CT lucencies were present in only one of these. The configuration of the patches of increased signal intensity was similar for both the normal and Alzheimer groups, but the extent of white-matter involvement was greater in the Alzheimer group.","Aged;Aging;Alzheimer Disease/ diagnosis;Female;Humans;Leukoencephalopathy, Progressive Multifocal/ diagnosis;Magnetic Resonance Spectroscopy;Male;Middle Aged","George, A. E.;de Leon, M. J.;Kalnin, A.;Rosner, L.;Goodgold, A.;Chase, N.",1986,Jul-Aug,,0,
4229,Parenchymal CT correlates of senile dementia (Alzheimer disease): loss of gray-white matter discriminability,"Neuropathologic studies have defined gross anatomic (structural) as well as histologic (parenchymal) changes of senile dementia (Alzheimer disease). This investigation suggests that loss of gray-white matter discriminability by computed tomography (CT) is related to cognitive impairment in this disease. Discriminability is defined as the relative ease of visual differentiation between gray and white tissues. Twenty-six elderly patients with dementia were subjected to extensive psychometric evaluation, a medical and neurologic examination, and CT scanning. Gray and white matter changes were assessed by subjectively evaluating three brain levels, the basal ganglia, the centrum semiovale, and the high convexity, on a five point scale. Quantitated gray and white matter scores were also obtained by sampling CT attenuation values. In addition, CT structural changes were evaluated by previously reported methods. there were significant correlations (P less than 0.05) between the subjectively assessed loss of gray-white matter discriminability at all brain levels and the measures of cognitive decline. At the high convexity level 91% of cognitive measures correlated with loss of gray-white discriminability. In the same patient group no gray-white discriminability correlation with age was demonstrated suggesting that gray-white discriminability does not simply change with age.","Aged;Atrophy;Brain/pathology/*radiography;Dementia/pathology/*radiography;Humans;Middle Aged;*Tomography, X-Ray Computed","George, A. E.;de Leon, M. J.;Ferris, S. H.;Kricheff, II",1981,May-Jun,,0,
4230,Short-term white matter alterations in Alzheimer's disease characterized by diffusion tensor imaging,"PURPOSE: To investigate whether there are any white matter changes in a 6-month follow-up of mild-moderate Alzheimer's patients using diffusion tensor imaging (DTI). MATERIALS AND METHODS: We recruited 18 mild-moderate Alzheimer's disease patients and they underwent magnetic resonance imaging (MRI) at recruitment and at 6-month follow-up. Diffusion MRI images were processed using DTI-ToolKit to create a population-based tensor template. This template was integrated with a voxel-wise and atlas-based analysis in FSL to determine the magnitude and location of change in diffusion metrics over the 6-month follow-up period. RESULTS: There were significant widespread changes in diffusion metrics across the entire white matter skeleton (P < 0.001), 95% confidence interval (CI) difference in fractional anisotropy: -0.007 (-0.011, -0.002), mean diffusivity: 0.040 (0.023, 0.058), axial diffusivity: 0.015 (0.008, 0.022), radial diffusivity: 0.012 (0.006, 0.019), as well as regions of interest in the splenium and superior longitudinal fasciculus. CONCLUSION: Our findings show that diffusion metrics are altered in a 6-month follow-up period of mild-moderate Alzheimer's patients, supporting the potential of DTI metrics to act as sensitive biomarkers for disease progression even over a relatively short time interval, and the potential utility to be applied to clinical trials of putative disease-modifying therapies. J. MAGN. RESON. IMAGING 2016;43:627-634.",,"Genc, S.;Steward, C. E.;Malpas, C. B.;Velakoulis, D.;O'Brien, T. J.;Desmond, P. M.",2016,Mar,10.1002/jmri.25017,0,
4231,A comparison of Tc-99m HM-PAO and I-123 IMP cerebral SPECT images in Alzheimer's disease and multi-infarct dementia,"SPECT images of the brain can be obtained using either 123I labelled amines or 99mTc-hexamethylpropyleneamineoxime (HM-PAO). Both materials produce images which are blood flow dominated and so appear similar in normal subjects, although the respective mechanisms of uptake are not yet finally established. It seems likely, however, that the different mechanisms of uptake are responsible for recent reports of some differences seen in images obtained with the two types of agent in patients with cerebral pathology, mainly cerebrovascular disease. In this study, 12 demented patients, 6 with dementia of the Alzheimer type (DAT) and 6 with multi infarct dementia (MID), were imaged with 123I-isopropylamphetamine (IMP) and 99mTc-HM-PAO and the images compared. Significantly more lesions were seen with IMP than HM-PAO (P less than 0.02); out of a possible 120 sites, 41 lesions were seen with IMP compared to 28 with HM-PAO, 23 being seen with both agents. However, it is concluded that either agent can be used for the differential diagnosis of dementia, a task for which the new cerebral blood flow agents seem well suited.","Aged;Aged, 80 and over;Alzheimer Disease/ radionuclide imaging;Amphetamines;Brain/ radionuclide imaging;Dementia, Multi-Infarct/ radionuclide imaging;Humans;Iodine Radioisotopes;Iofetamine;Middle Aged;Organometallic Compounds;Oximes;Technetium;Technetium Tc 99m Exametazime;Tomography, Emission-Computed","Gemmell, H. G.;Sharp, P. F.;Besson, J. A.;Ebmeier, K. P.;Smith, F. W.",1988,,,0,
4232,Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex,"We describe an atypical neuropatholgical phenotype of sporadic Creutzfeldt-Jakob disease (sCJD) in a 64-year-old man presenting with a 5-month history of rapidly progressive dementia, comprising behavioral disturbances, memory complaints, disorientation and language alterations. MRI showed diffuse atrophy and hyperintensities in parietal, occipital, temporal and frontal cortices and left caudate nucleus on T2-weighted and fluid-attenuated inversion recovery images. No typical EEG alterations were observed. Repeated 14-3-3 assay was positive after a first negative test. Neuropathology showed classical CJD changes with small cortical foci of large confluent vacuoles and relatively well-preserved cerebellar cortex. The most striking feature was the presence of abundant Kuru-type plaques in both cerebral cortex and subcortical white matter. Sparse Kuru-type plaques were also seen in cerebellum, although only in white matter. Immunohistochemistry showed, in addition to unicentric plaques, diffuse synaptic and patchy perivacuolar, as well as plaque-like and periaxonal pathological prion protein deposits (PrP(res)). Western blot studies demonstrated the co-occurrence of PrP(res) types 1 and 2 in frontal cortex and a relatively weak type 2 signal in cerebellum. PRNP genotyping revealed methionine homozygosity at codon 129 and excluded mutations. This case shows a previously undescribed combination of histopathological features which preclude its classification according to the current phenotypic and molecular sCJD classification. The observation demonstrates that Kuru-type amyloid plaques mainly involving the cerebral white matter may also occur in sCJD cases with short clinical course and the co-existence of PrP(res) types 1 and 2. This case further highlights the complexity of the correlations between histopathological phenotype and PrP(res) isotype in prion diseases. © 2012 Japanese Society of Neuropathology.",,"Gelpi, E.;Soler Insa, J. M.;Parchi, P.;Saverioni, D.;Yagüe, J.;Nos, C.;Martínez- Saez, E.;Ribalta, T.;Ferrer, I.;Sanchez-Valle, R.",2013,April,,0,
4233,"Demonstration of safety of intravenous immunoglobulin in geriatric patients in a long-term, placebo-controlled study of Alzheimer's disease","Introduction We present safety results from a study of Gammagard Liquid intravenous immunoglobulin (IGIV) in patients with probable Alzheimer's disease. Methods This was a placebo-controlled double-blind study. Subjects were randomized to 400 mg/kg (n = 127), 200 mg/kg (n = 135) IGIV, or to 0.25% human albumin (n = 121) administered every 2 weeks +/- 7 days for 18 months. Results Elevated risk ratios of IGIV versus placebo included chills (3.85) in 9.5% of IGIV-treated subjects (all doses), compared to 2.5% of placebo-treated subjects, and rash (3.08) in 15.3% of IGIV-treated subjects versus 5.0% of subjects treated with placebo. Subjects in the highest IGIV dose group had the lowest proportion of SAEs considered related to product (2 of 127 [1.6%]). Subjects treated with IGIV experienced a lower rate of respiratory and all other infections compared to placebo. Discussion IGIV-treated subjects did not experience higher rates of renal failure, lung injury, or thrombotic events than the placebo group. There were no unexpected safety findings. IGIV was well tolerated throughout 18 months of treatment in subjects aged 50-89 years.",adult;aged;Alzheimer disease dt [Drug Therapy];anaphylaxis si [Side Effect];anemia si [Side Effect];artery thrombosis si [Side Effect];arthralgia si [Side Effect];article;bradycardia si [Side Effect];brain edema si [Side Effect];brain hemorrhage si [Side Effect];brain infarction si [Side Effect];cerebrovascular accident si [Side Effect];chill si [Side Effect];clinical assessment;cohort analysis;confusion si [Side Effect];congestive heart failure si [Side Effect];controlled study;contusion si [Side Effect];diarrhea si [Side Effect];dizziness si [Side Effect];dose response;double blind procedure;drug efficacy;drug megadose;drug safety;drug tolerability;drug withdrawal;epistaxis si [Side Effect];extravasation si [Side Effect];female;focal epilepsy si [Side Effect];geriatric patient;headache si [Side Effect];heart infarction si [Side Effect];human;hypertension si [Side Effect];infection si [Side Effect];insomnia si [Side Effect];insomnia si [Side Effect];kidney failure si [Side Effect];laceration si [Side Effect];low drug dose;lung embolism si [Side Effect];lung injury si [Side Effect];major clinical study;male;mental disease si [Side Effect];nausea si [Side Effect];nuclear magnetic resonance imaging;outcome assessment;phase 3 clinical trial;priority journal;randomized controlled trial;rash si [Side Effect];rash dt [Drug Therapy];respiratory tract disease si [Side Effect];risk assessment;side effect si [Side Effect];statistical analysis;thromboembolism si [Side Effect];thrombosis si [Side Effect];upper respiratory tract infection si [Side Effect];urinary tract infection si [Side Effect];vomiting si [Side Effect];albumin;cetirizine dt [Drug Therapy];cholinesterase inhibitor dt [Drug Therapy];cortisone dt [Drug Therapy];dexamethasone dt [Drug Therapy];diphenhydramine dt [Drug Therapy];hemoglobin ec [Endogenous Compound];immunoglobulin ae [Adverse Drug Reaction];immunoglobulin dt [Drug Therapy];immunoglobulin iv [Intravenous Drug Administration];immunoglobulin ct [Clinical Trial];loratadine dt [Drug Therapy];memantine dt [Drug Therapy];methylprednisolone dt [Drug Therapy];placebo;prednisone dt [Drug Therapy],"Gelmont, D.;Thomas, R. G.;Britt, J.;Dyck-Jones, J. A.;Doralt, J.;Fritsch, S.;Brewer, J. B.;Rissman, R. A.;Aisen, P.",2016,,,0,
4234,Causes of urinary incontinence after acute hemispheric stroke,"Background and Purpose: We prospectively studied bladder function in stroke patients to determine the mechanisms responsible for poststroke urinary incontinence. Methods: Fifty-one patients with recent unilateral ischemic hemispheric stroke admitted to a neurorehabilitation unit were enrolled. The presence of urinary incontinence was correlated with infarct location, neurological deficits, and functional status. Urodynamic studies were performed on all incontinent patients. Results: Nineteen patients (37%) were incontinent. Incontinence was associated with large infarcts, aphasia, cognitive impairment, and functional disability (p<0.05) but not with age, sex, side of stroke, or time from stroke to entry in the study. Urodynamic studies, performed on all 19 incontinent patients, revealed bladder hyperreflexia in 37%, normal studies in 37%, bladder hyporeflexia in 21%, and detrusor-sphincter dyssynergia in 5%. All of the patients with normal urodynamic studies were aphasic, demented, or severely functionally impaired. All of the patients with hyporeflexic bladders had underlying diabetes or were taking anticholinergic medications. Forty-six percent of incontinent patients treated with scheduled voiding alone were continent at discharge compared with 17% of patients treated pharmacologically. Conclusions: There are three major mechanisms responsible for poststroke urinary incontinence: 1) disruption of the neuromicturition pathways, resulting in bladder hyperreflexia and urgency incontinence; 2) incontinence due to stroke- related cognitive and language deficits, with normal bladder function; and 3) concurrent neuropathy or medication use, resulting in bladder hyporeflexia and overflow incontinence. Urodynamic studies are of benefit in establishing the cause of incontinence. Scheduled voiding is a useful first-line treatment in many cases of incontinence.",alpha adrenergic receptor blocking agent;cholinergic receptor blocking agent;flavoxate;imipramine;oxybutynin;prazosin;spasmolytic agent;terazosin;aged;aphasia;article;bladder dysfunction;bladder function;brain infarction;cognitive defect;computer assisted tomography;detrusor dyssynergia;disease association;female;functional disease;human;intermittent catheterization;major clinical study;male;micturition;nuclear magnetic resonance imaging;priority journal;scoring system;cerebrovascular accident;urine incontinence;urodynamics,"Gelber, D. A.;Good, D. C.;Laven, L. J.;Verhulst, S. J.",1993,,,0,
4235,Associations of current and remitted major depressive disorder with brain atrophy: the AGES-Reykjavik Study,"BACKGROUND: To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia. METHOD: Within the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 4354 persons (mean age 76 +/- 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI). RESULTS: Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = -1.25%, 95% confidence interval (CI) -2.05 to -0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = -1.62%, 95% CI -3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI -0.54 to 0.66). CONCLUSIONS: In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia.","Age of Onset;Aged;Aged, 80 and over;Atrophy/epidemiology/pathology;Brain/ pathology;Cohort Studies;Cross-Sectional Studies;Dementia/diagnosis;Depressive Disorder, Major/diagnosis/ epidemiology/ pathology;Female;Humans;Iceland/epidemiology;Interview, Psychological;Linear Models;Magnetic Resonance Imaging/methods;Male;Recurrence;Remission, Spontaneous","Geerlings, M. I.;Sigurdsson, S.;Eiriksdottir, G.;Garcia, M. E.;Harris, T. B.;Sigurdsson, T.;Gudnason, V.;Launer, L. J.",2013,Feb,10.1017/s0033291712001110,0,
4236,"Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia","OBJECTIVE: We investigated the associations of morning and evening salivary cortisol levels with regional brain volumes and cognitive functioning in community-dwelling older persons without dementia. METHOD: From the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons without dementia (age 76 +/- 5 years, 58% women) who had 1.5T brain MRI, assessment of cognitive functioning, and saliva collected at home 45 minutes after awakening and at night. Linear regression analysis was used to estimate the cross-sectional relationship among cortisol levels, brain volumes, and cognitive functioning, adjusting for covariates. RESULTS: Higher evening cortisol was associated with smaller total brain volume (highest vs lowest tertile -16.0 mL; 95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education, intracranial volume, smoking, steroid use, white matter lesions, and brain infarcts on MRI). The smaller volumes were observed in all brain regions, but were significantly smaller in gray matter than in white matter regions. Poorer cognitive functioning across all domains was also associated with higher evening cortisol. Higher levels of morning cortisol were associated with slightly greater normal white matter volume and better processing speed and executive functioning, but not with gray matter volume or with memory performance. CONCLUSIONS: In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function. Understanding these differential associations may aid in developing strategies to reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late-life cognitive impairment.","Adult;Aged;Aged, 80 and over;Aging;Brain/*pathology;Cognition/*physiology;Cognition Disorders/physiopathology;Cross-Sectional Studies;Dementia/pathology;Female;Humans;Hydrocortisone/*analysis;Male;Memory/physiology;Middle Aged;Neuropsychological Tests;Pituitary-Adrenal System/pathology;Saliva/chemistry/*physiology","Geerlings, M. I.;Sigurdsson, S.;Eiriksdottir, G.;Garcia, M. E.;Harris, T. B.;Gudnason, V.;Launer, L. J.",2015,Sep 15,10.1212/wnl.0000000000001931,0,
4237,"Depressive symptoms, antidepressant use, and brain volumes on MRI in a population-based cohort of old persons without dementia","We examined whether late-life depression, including depressive symptoms and antidepressant use, was associated with smaller total brain volume, smaller hippocampal volume, and larger white matter hyperintensity (WMH) volume in a large community-based cohort of old persons without dementia. Within the Washington/Hamilton Height-Inwood Columbia Aging Project (WHICAP), a community-based cohort study in northern Manhattan, 630 persons without dementia (mean age 80 years, SD = 5) had volumetric measures of the total brain, hippocampus, and WMH at 1.5 Tesla MRI and data on current depression, defined as a score of 4 or higher on the 10-item Center for Epidemiologic Studies-Depression (CES-D) scale, or use of antidepressants. Multiple linear regression analyses adjusted for age, gender, ethnicity, education, cardiovascular disease history, and MRI parameters showed that subjects with current depression had smaller relative total brain volume (B = -0.86%; 95% CI -1.68 to -0.05%; p < 0.05), smaller relative hippocampal volume (B = -0.07 ml; 95% CI -0.14 to 0.00 ml; p = 0.05), and larger relative WMH volume (natural logtransformed B = 0.19 ml; 95% CI 0.02 to 0.35 ml; p < 0.05). When examined separately, antidepressant use was significantly associated with smaller total brain, smaller hippocampal, and larger WMH volume, while high CES-D scores were not significantly associated with any of the brain measures, although the direction of association was similar as for antidepressant use. With the caveat that analyses were cross-sectional and we had no formal diagnosis of depression, our findings suggest that in this community-based sample of old persons without dementia, late-life depression is associated with more brain atrophy and more white matter lesions, which was mainly driven by antidepressant use.","Aged;Aged, 80 and over;Antidepressive Agents/*therapeutic use;Brain/*pathology;Cohort Studies;Depression/*drug therapy/epidemiology/*pathology;Female;Humans;Image Processing, Computer-Assisted;Linear Models;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Psychiatric Status Rating Scales;Residence Characteristics","Geerlings, M. I.;Brickman, A. M.;Schupf, N.;Devanand, D. P.;Luchsinger, J. A.;Mayeux, R.;Small, S. A.",2012,,10.3233/jad-2012-112009,0,
4238,"HFE H63D, C282Y and AGTR1 A1166C polymorphisms and brain white matter lesions in the aging brain","Incidental white matter lesions (WML) are a common neuroradiological finding in elderly people and have been linked to dementia and depression. Various mechanisms including hypoxia and increased production of reactive oxygen species (ROS) are implicated in the etiology of WML. The hemochromatosis (HFE) gene p.H63D and p.C282Y polymorphisms have been linked to dysregulation of iron metabolism and increased levels of ROS, whereas Angiotensin II receptor 1 (AGTR1) c.1166A --> C polymorphism is known as a vascular risk factor. These genetic polymorphisms were characterized in brains donated to the UK MRC Cognitive Function and Ageing Study (CFAS) to assess their potential role in the risk for development of age-related WML. The study cohort comprised 258 brain donated to CFAS. WML severity was assessed in the postmortem brain donations using magnetic resonance imaging (MRI) scans and scored using the Scheltens' scale. Polymerase chain reaction (PCR) amplification of extracted DNA followed by restriction enzyme digestion was used to genotype the samples. Genotypes were validated using direct sequencing in a smaller sample. The results show that HFE p.H63D polymorphism is not associated with WML severity in the whole cohort. However, there is a significant association of the D allele with severity of WML in noncarriers of the APOE epsilon4 allele. No association is demonstrated between the HFE p.C282Y nor the AGTR1 c.1166A --> C polymorphisms and WML severity. The HFE gene appears to be a genetic risk factor for severe aging WML independently of the APOE epsilon4 genotype. This would support the role of iron-related oxidative stress, in addition to previously studied factors, e.g., hypoxia as potential risk factors for developing prominent aging WML.","Aged;Aged, 80 and over;Aging/ pathology;Amino Acids/genetics;Brain/ pathology;Female;Gene Frequency;Genetic Predisposition to Disease;Genotype;Histocompatibility Antigens Class I/ genetics;Humans;Leukoencephalopathies/ genetics/ pathology;Magnetic Resonance Imaging/methods;Male;Membrane Proteins/ genetics;Middle Aged;Polymorphism, Single Nucleotide;Receptor, Angiotensin, Type 1/ genetics;Risk Factors","Gebril, O. H.;Kirby, J.;Savva, G.;Brayne, C.;Ince, P. G.",2011,Mar,10.3109/01677063.2011.556206,0,
4239,Whole brain imaging of HIV-infected patients: quantitative analysis of magnetization transfer ratio histogram and fractional brain volume,"BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) histogram analysis and volumetric MR imaging are sensitive tools with which to quantify the tissue destructive effects in patients with white matter or neurodegenerative disease. Our purpose was to determine whether whole brain MTR and fractional brain parenchyma volume measurements are altered in HIV-1-infected patients who are neurologically symptomatic and in those who are asymptomatic. METHODS: We performed MR imaging and MTR studies of 15 neurologically symptomatic (seven patients) and asymptomatic (eight patients) HIV-1-seropositive patients and compared their findings with those of 10 seronegative normal control participants. MTR was computed on the basis of whole brain parenchyma segmented by using thin section dual echo MR images. RESULTS: The loss of brain tissue, indicated by fractional brain parenchyma volume, was more pronounced in neurologically symptomatic patients (P =.003) but not in asymptomatic patients (P =.23) when compared with control participants. As for whole brain MTR histogram analysis, both patient groups showed significant decrease in mean (P =.02) and median (P < or =.009) values, compared with normal control participants. There was a trend toward positive correlation (r > or = 0.56) between MTR histogram statistics and fractional brain parenchyma volume. CONCLUSION: Our results suggest that MTR histogram analysis is sensitive in detecting early involvement in neurologically asymptomatic patients with HIV and may, therefore, be used as a combined tool with volumetric measurement, which showed significant tissue loss only in symptomatic patients, to assess various stages of brain damage induced by HIV.","AIDS Dementia Complex/ diagnosis;Adult;Atrophy;Brain/ pathology;Brain Damage, Chronic/diagnosis;Female;HIV Seropositivity/ diagnosis;Hiv-1;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination;Sensitivity and Specificity","Ge, Y.;Kolson, D. L.;Babb, J. S.;Mannon, L. J.;Grossman, R. I.",2003,Jan,,0,
4240,A novel cysteine-sparing NOTCH3 mutation in a Chinese family with CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset cerebral small vessel disorder caused by the mutations of the neurogenic locus notch homolog protein 3 (NOTCH3) gene. The extracellular part of NOTCH3 is composed of 34 epidermal growth factor-like (EGF-like) repeat domains. Each EGF-like domain is rich of cysteine and glycine to produce three loops that are essential for high-affinity binding to its ligand. Nearly all reported CADASIL-associated mutations result in gain or loss of a cysteine residue within the EGF-like domains. Only a few cysteine-sparing NOTCH3 mutations have been documented in the patients with CADASIL to date. Here, we reported a Chinese CADASIL family with a cysteine-sparing NOTCH3 mutation. In this family, affected patients had dizziness, memory loss, gait instability, or hemiplegia. Brain magnetic resonance imaging (MRI) showed diffuse leukoencephalopathy with confluent signal abnormalities in the periventricular white matter, basal ganglia, and centrum semiovale bilaterally. By screening the entire coding region of NOTCH3, a novel missense mutation p.G149V (c.446G>T) was found. This mutation was not detected in 400 normal controls. Considering the critical position of glycine within the C-loop of EGF-like domain and its high conservation through evolution, p.G149V mutation could be a potential pathogenic cause for CADASIL.","Adult;Amino Acid Substitution;Brain/metabolism/physiopathology/radiography;CADASIL/ genetics/metabolism/physiopathology/radiography;Female;Humans;Male;Mutation, Missense;Protein Structure, Tertiary;Receptors, Notch/ genetics/metabolism;Repetitive Sequences, Amino Acid","Ge, W.;Kuang, H.;Wei, B.;Bo, L.;Xu, Z.;Xu, X.;Geng, D.;Sun, M.",2014,,10.1371/journal.pone.0104533,0,
4241,Spatial navigation in young versus older adults,"Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18-26 years old) and 44 older participants stratified as participants 60-70 years old (n = 24) and participants 71-84 years old (n = 20). All underwent spatial navigation testing in the real-space human analog of the Morris Water Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the eight consecutive trials, trials 2-8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71-84 years old (p < 0.001), but not those 60-70 years old, showed deficits in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p' s = 0.01). There were no gender differences in spatial navigation and learning. Linear regression limited to older participants showed linear (ß = 0.30, p = 0.045) and quadratic (ß = 0.30, p = 0.046) effect of age on allocentric navigation. There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer's disease. © 2013 Gazova, Laczó, Rubinova, Mokrisova, Hyncicova, Andel, Vyhnalek, Sheardova, Coulson and Hort.",adult;age;aged;allocentric navigation;article;egocentric navigation;female;hippocampus;human;human experiment;male;mental performance;middle aged;Morris water maze test;neuropsychological test;normal human;nuclear magnetic resonance imaging;parietal lobe;sex difference;spatial learning;spatial orientation;spatial navigation test;task performance;very elderly;young adult,"Gazova, I.;Laczó, J.;Rubinova, E.;Mokrisova, I.;Hyncicova, E.;Andel, R.;Vyhnalek, M.;Sheardova, K.;Coulson, E. J.;Hort, J.",2013,,,0,
4242,Body mass index and magnetic resonance markers of brain integrity in adults,"Objective: Obesity and being overweight during adulthood have been consistently linked to increased risk for development of dementia later in life, especially Alzheimer's disease. They have also been associated with cognitive dysfunction and brain structural alterations in otherwise healthy adults. Although proton magnetic resonance spectroscopy may distinguish between neuronal and glial components of the brain and may point to neurobiological mechanisms underlying brain atrophy and cognitive changes, no spectroscopic studies have yet assessed the relationships between adiposity and brain metabolites. Methods: We have utilized magnetic resonance imaging and proton magnetic resonance spectroscopic imaging data from 50 healthy middle-aged participants (mean age, 41.7 ± 8.5 years; 17 women), who were scanned as control subjects for another study. Results: After adjustment for age and sex, greater body mass indices (BMIs) correlated with: (1) lower concentrations of N-acetylaspartate (spectroscopic marker of neuronal viability) in frontal (p = 0.001), parietal (p = 0.006), and temporal (p = 0.008) white matter; (2) lower N-acetylaspartate in frontal gray matter (p = 0.01); and (3) lower concentrations of choline-containing metabolites (associated with membrane metabolism) in frontal white matter (p = 0.05). Interpretation: These results suggest that increased BMI at midlife is associated with neuronal and/or myelin abnormalities, primarily in the frontal lobe. Because white matter in the frontal lobes is more prone to the effects of aging than in other lobes, our results may reflect accelerated aging in individuals with high levels of adiposity. Thus, greater BMI may increase the odds of developing an age-related disease, such as Alzheimer's disease. © 2008 American Neurological Association. Published by Wiley-Liss, Inc., through Wiley Subscription Services.",,"Gazdzinski, S.;Kornak, J.;Weiner, M. W.;Meyerhoff, D. J.",2008,May,,0,
4243,Combining functional and structural brain magnetic resonance imaging in Huntington disease,"OBJECTIVE: To concurrently investigate with magnetic resonance (MR) the brain activation and regional brain atrophy in patients with Huntington disease (HD). METHODS: Nine symptomatic HD patients and 11 healthy subjects underwent an MR study including functional MR acquisition during finger tapping of the right hand and high-resolution T1-weighted images. Functional and structural data were analyzed using Statistical Parametric Mapping 2 software. RESULTS: As compared with control subjects, HD patients showed decreased activation in the left caudate nucleus and medial frontal and anterior cingulate gyri and increased activation in the right supplementary motor area and supramarginal gyrus and left intraparietal sulcus. The pattern of atrophy included thinning of the gray matter (GM) in the insula, inferior frontal gyrus, caudate, lentiform nucleus, and thalamus, bilaterally, in the left middle frontal, middle occipital, and middle temporal gyri, and of periventricular, subinsular, right temporal lobe, and left internal capsule white matter. Only the decreased activation in the caudate nucleus correlated topographically with the caudate GM loss. CONCLUSION: The cortical areas of functional changes do not correspond to those of GM atrophy in patients with HD and are likely to reflect decreased output of the motor basal ganglia-thalamo-cortical circuit and compensatory recruitment of accessory motor pathways.",Atrophy;Brain/pathology/physiopathology;Cerebral Cortex/pathology/physiopathology;Female;Humans;Huntington Disease/ diagnosis;Magnetic Resonance Imaging/ methods;Male;Middle Aged,"Gavazzi, C.;Nave, R. D.;Petralli, R.;Rocca, M. A.;Guerrini, L.;Tessa, C.;Diciotti, S.;Filippi, M.;Piacentini, S.;Mascalchi, M.",2007,Jul-Aug,10.1097/01.rct.0000284390.53202.2e,0,
4244,"Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial","Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease. Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11). Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6.32, 95% CI 5.31-7.34]: 75 mg LMTM twice a day [n=257] -0.02, -1.60 to 1.56, p=0.9834, 125 mg LMTM twice a day [n=250] -0.43, -2.06 to 1.20, p=0.9323; change in ADCS-ADL score compared with control [-8.22, 95% CI -9.63 to -6.82]: 75 mg LMTM twice a day -0.93, -3.12 to 1.26, p=0.8659; 125 mg LMTM twice a day -0.34, -2.61 to 1.93, p=0.9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants. Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon. Funding TauRx Therapeutics. Copyright 2016 Elsevier Ltd",abnormal laboratory result;activity of daily living assessment;adverse outcome;aged;Alzheimer disease;Alzheimer Disease Assessment Scale;Alzheimer Disease Assessment Scale cognitive subscale;Alzheimer Disease Co operative Study Activities of Daily Living Inventory scale;article;clinical effectiveness;controlled study;convulsion si [Side Effect];daily life activity;disease course;disease severity;double blind procedure;drug efficacy;drug megadose;drug safety;drug withdrawal;feces color;female;heart infarction si [Side Effect];hemoglobin determination;hemolytic anemia si [Side Effect];human;intention to treat analysis;low drug dose;major clinical study;male;outcome assessment;phase 1 clinical trial (topic);phase 3 clinical trial;positron emission tomography;priority journal;protein aggregation;randomized controlled trial;serotonin syndrome si [Side Effect];side effect si [Side Effect];treatment duration;treatment response;urinalysis;amyloid ec [Endogenous Compound];antidepressant agent cb [Drug Combination];cholinesterase inhibitor cb [Drug Combination];leuco methylthioninium bis(hydromethanesulfonate ae [Adverse Drug Reaction];leuco methylthioninium bis(hydromethanesulfonate ct [Clinical Trial];leuco methylthioninium bis(hydromethanesulfonate po [Oral Drug Administration];leuco methylthioninium bis(hydromethanesulfonate pd [Pharmacology];memantine cb [Drug Combination];methylene blue ae [Adverse Drug Reaction];methylene blue ct [Clinical Trial];methylene blue po [Oral Drug Administration];methylene blue pd [Pharmacology];neuroleptic agent cb [Drug Combination];protein inhibitor ae [Adverse Drug Reaction];protein inhibitor ct [Clinical Trial];protein inhibitor po [Oral Drug Administration];protein inhibitor pd [Pharmacology];sedative agent cb [Drug Combination];serotonin uptake inhibitor;tau protein ec [Endogenous Compound];unclassified drug;adverse drug reaction;Asia;clinical trial;congenital malformation;controlled clinical trial;disease assessment;disease carrier;European Union;funding;gastrointestinal tract;gene inactivation;human tissue;imaging;methemoglobinemia;multicenter study;North America;oxidation;parallel design;randomization;register;Russian Federation;safety;side effect;tablet;urine;visually impaired person;endogenous compound;hemoglobin,"Gauthier, S.;Feldman, H. H.;Schneider, L. S.;Wilcock, G. K.;Frisoni, G. B.;Hardlund, J. H.;Moebius, H. J.;Bentham, P.;Kook, K. A.;Wischik, D. J.;Schelter, B. O.;Davis, C. S.;Staff, R. T.;Bracoud, L.;Shamsi, K.;Storey, J. M. D.;Harrington, C. R.;Wischik, C. M.",2017,,,0,
4245,"Vascular risk factors, white matter hyperintensities and hippocampal volume in normal elderly individuals","BACKGROUND/AIMS: Hippocampal atrophy has been identified as marker for the development of Alzheimer's dementia (AD). To what extent vascular risk factors and white matter hyperintensities (WMH) affect hippocampal volume (HV) in asymptomatic elderly subjects and thus may impact such a predictive capacity is controversial. METHODS: We analysed 287 participants of the Austrian Stroke Prevention Study (mean age 66.6 +/- 6.6 years) with a Mini Mental State Examination score >/=27 who were free of neuropsychiatric disease and had undergone MRI including coronal T(1)-weighted sequences allowing for semi-automatic assessment of HV. Global brain volume (BV) was measured using SIENAX. WMH were rated according to the Fazekas scale and segmented to obtain WMH volumes. RESULTS: Higher age was associated with lower absolute and normalized HV, a lower BV and higher WMH volume. None of the vascular risk factors had an impact on HV except for high-density lipoprotein. This effect disappeared after normalization of HV. WMH severity and volume did not affect HV either. CONCLUSION: Our data indicate HV loss in parallel with the whole brain and suggest no specific vulnerability towards vascular risk factors or age-related WMH in a cognitively intact normal elderly population. This also supports the utility of HV measurements to identify impending AD.","Age Factors;Aged;Aged, 80 and over;Aging/physiology;Anatomy, Cross-Sectional;Atrophy;Austria;Brain/growth & development/*pathology;Cerebral Small Vessel Diseases/epidemiology/pathology;Cohort Studies;Data Interpretation, Statistical;Female;Hippocampus/*pathology;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/*epidemiology/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Reference Values;Risk Factors;Vascular Diseases/*epidemiology","Gattringer, T.;Enzinger, C.;Ropele, S.;Gorani, F.;Petrovic, K. E.;Schmidt, R.;Fazekas, F.",2012,,10.1159/000336052,0,
4246,White matter involvement in idiopathic Parkinson disease: a diffusion tensor imaging study,"BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) offers a unique window on the connectivity changes, extending beyond the basal ganglia, which accompany the cognitive symptoms of Parkinson disease (PD). The primary purpose of this study was to assess the microstructural damage to cerebral white matter occurring in idiopathic PD. MATERIALS AND METHODS: Our sample included patients with PD without dementia (n = 10; Hoehn and Yahr stages I and II; Unified Parkinson Disease Rating Scale, 20.5 +/- 8.3; and Mini-Mental State Examination, 28.3 +/- 1.5) and age-matched healthy control subjects (n = 10). DTI was performed on a 1.5T scanner, and mean diffusivity (MD) and fractional anisotropy (FA) maps were obtained. Regions of interest (ROIs) were drawn on the major fiber bundles as well as on gray matter nuclei. RESULTS: In patients, the MD was increased at borderline significance in the substantia nigra but was unaltered in the thalamus, globus pallidus, putamen, and in the head of the caudate nucleus. The FA and MD were unaltered in the corticospinal tract in the midbrain and at the level of the internal capsule, and in the splenium of the corpus callosum. By contrast, the MD was increased and the FA was decreased in the genu of the corpus callosum and in the superior longitudinal fasciculus; in the cingulum, only the MD was altered. The observed changes were not significantly lateralized. CONCLUSIONS: Widespread microstructural damage to frontal and parietal white matter occurs already in the early stages of PD.","Brain/ pathology;Dementia/ complications/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Parkinson Disease/ complications/ pathology;Sensitivity and Specificity","Gattellaro, G.;Minati, L.;Grisoli, M.;Mariani, C.;Carella, F.;Osio, M.;Ciceri, E.;Albanese, A.;Bruzzone, M. G.",2009,Jun,10.3174/ajnr.A1556,0,
4247,"Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases","Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial 18F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels. Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (-16%, left; -12%, right) and caudate nucleus (-18%, left; -18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (-48%), occipital cortex (-21%), and precuneus (-19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (-12%) and occipital cortex (-15%). Also, by 24 months, most of the amyloid had been cleared and the patient demonstrated improved results on the Rivermead symptom questionnaire, Glasgow Outcome Scale-Extended, and Disability Rating Scale. With respect to APOE status, the patient in Case 1 had two epsilon3 alleles and the patient in Case 2 had one epsilon2 and one epsilon3 allele. In comparison to the findings of the initial scan at 1 month after TBI, by 12 and 24 months after injury amyloid was cleared in some brain regions and increased in others. Serial imaging conducted here suggests that florbetapir F18 PET imaging may be useful in monitoring amyloid dynamics within specific brain regions following severe TBI and may be predictive of cognitive deficits.",,"Gatson, J. W.;Stebbins, C.;Mathews, D.;Harris, T. S.;Madden, C.;Batjer, H.;Diaz-Arrastia, R.;Minei, J. P.",2015,Nov 27,10.3171/2015.6.jns15639,0,
4248,Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder,"Objective: To investigate whether intensification of combined antiretroviral therapy (cART) with the CC chemokine receptor type 5 (CCR5) entry inhibitor maraviroc leads to improvement in global neurocognitive functioning in virally suppressed men with HIV-associated neurocognitive disorder (HAND). Design: Prospective, double observer-blinded, open-label pilot randomized-controlled trial. Participants were randomized to remain on their existing cART regimen (control arm; n=8) or receive maraviroc-intensification (maraviroc arm; n=9). Methods: Participants completed a five-domain neuropsychological battery at baseline, 6-and 12-month visits. Raw scores were transformed into age-corrected z-scores and averaged into a global z-score. Single voxel (1 H)-magnetic resonance spectroscopy (MRS) major cerebral metabolite concentrations were collected at baseline and 12 months in the basal ganglia and frontal white matter and quantified using jMRUI. Neuroinflammatory biomarkers cerebrospinal fluid neopterin and β 2-microglobulin were also measured. Results: Fourteen of the 17 participants completed the study: nine maraviroc arm and five control. We found medium to large effect sizes in favour of improved global neurocognitive performance in the maraviroc arm over time {armtime interaction: P<.05; 6 month: [β=-0.10, standard error(SE)=0.04, 90% confidence interval(90%CI)=-0.18,.03; P<0.03] yielding a large effect-size d=0.77 (90%CI=-0.19,1.71); 12 month: [β=-0.01; SE=0.05; 90%CI=-0.09, 0.06; P<0.77] yielding a moderate effect-size d=0.55 (90%CI=-0.47,1.55)}. No treatment-related changes were detected for 1 H-MRS metabolites or cerebrospinal fluid biomarkers. Conclusion: This pilot study provides feasibility, tolerability, proof-of-concept and preliminary evidence for clinically relevant neurocognitive improvement in cART enhancement with maraviroc in virally suppressed HAND patients. Lack of concomitant brain metabolite and biomarker change may be related to complex dynamics of brain repair.",NCT01449006;anti human immunodeficiency virus agent;beta 2 microglobulin;choline;creatine;glutamic acid;glutamine;inositol;maraviroc;n acetylaspartic acid;neopterin;adult;antiviral therapy;article;brain level;brain metabolism;clinical article;controlled study;double blind procedure;drug efficacy;drug tolerability;feasibility study;female;HIV associated dementia;human;intervention study;male;middle aged;neuropsychological test;open study;phase 4 clinical trial;pilot study;priority journal;prospective study;protein cerebrospinal fluid level;proton nuclear magnetic resonance;randomized controlled trial;treatment outcome,"Gates, T. M.;Cysique, L. A.;Siefried, K. J.;Chaganti, J.;Moffat, K. J.;Brew, B. J.",2016,,,0,
4249,1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment,"BACKGROUND: White matter hyperintensities (WMHs) are associated with vascular cognitive impairment (VCI) but fail to correlate with neuropsychological measures. As proton MR spectroscopy ((1)H-MRS) can identify ischaemic tissue, we hypothesised that MRS detectable brain metabolites would be superior to WMHs in predicting performance on neuropsychological tests. METHODS: 60 patients with suspected VCI underwent clinical, neuropsychological, MRI and CSF studies. They were diagnosed as having subcortical ischaemic vascular disease (SIVD), multiple infarcts, mixed dementia and leukoaraiosis. We measured brain metabolites in a white matter region above the lateral ventricles with (1)H-MRS and WMH volume in this region and throughout the brain. RESULTS: We found a significant correlation between both total creatine (Cr) and N-acetylaspartyl compounds (NAA) and standardised neuropsychological test scores. Cr levels in white matter correlated significantly with executive function (p=0.001), attention (p=0.03) and overall T score (p=0.007). When lesion volume was added as a covariate, NAA also showed a significant correlation with executive function (p=0.003) and overall T score (p=0.015). Furthermore, while metabolite levels also correlated with total white matter lesion volume, adjusting the Cr levels for lesion volume did not diminish the strength of the association between Cr levels and neuropsychological scores. The lowest metabolite levels and neuropsychological scores were found in the SIVD group. Finally, lesion volume alone did not correlate significantly with any neuropsychological test score. CONCLUSION: These results suggest that estimates of neurometabolite levels provide additional and useful information concerning cognitive function in VCI not obtainable by measurements of lesion load.","Aged;Aged, 80 and over;Alzheimer Disease/etiology/psychology;Aspartic Acid/analogs & derivatives/blood;Biomarkers/blood;Brain Ischemia/psychology;Choline/blood;Cognition Disorders/etiology/psychology;Creatine/blood;Data Interpretation, Statistical;Dementia, Vascular/*metabolism/pathology/*psychology;*Executive Function;Female;Humans;Leukoaraiosis/etiology;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Memory/physiology;Middle Aged;Neuropsychological Tests;Regression Analysis;Mri;Mrs;Neurochemistry;Neuropsychiatry;Vascular Dementia","Gasparovic, C.;Prestopnik, J.;Thompson, J.;Taheri, S.;Huisa, B.;Schrader, R.;Adair, J. C.;Rosenberg, G. A.",2013,Jul,10.1136/jnnp-2012-303878,0,
4250,Diagnostic imaging in dementia: use of imaging modalities in Dutch memory clinics,"PURPOSE: To evaluate the use of MRI and CT in the diagnostic work-up of dementia in Dutch memory clinics, and to analyse the rationale for choosing each modality. MATERIALS AND METHODS: A digital survey was sent by e-mail to all medical specialists (n=235) working at a memory clinic in the Netherlands. RESULTS: The survey was completed by 64% (151). 85% of the respondents were geriatricians, 13% neurologists and 2% other, working at a total of 69 clinics. 40% variably orders CT or MRI, 37% orders MRI, 19% CT, and 4% CT plus MRI. Primary factors influencing this choice are: MRI contraindications, physical limitations, age, vascular or oncological medical history, and waiting time. With CT, 87% indicates information is lacking: vascular disease/white matter lesions, (hippocampal) atrophy, and specific pathologies (metastases, amyloid angiopathy). Furthermore, respondents prefer MRI because they can assess the images more easily themselves. Only 50% of respondents indicate that CT protocol dictates coronal reconstructions. Additionally, these reconstructions are not provided consistently. Rating-scales are used to describe images in 5%. In 75% assessment is not uniform. CONCLUSION: MRI is preferred over CT in diagnostic imaging of dementia, in accordance with existing guidelines. However, these guidelines are mostly out-dated and modern multislice CT potential is relatively unknown among geriatricians. In memory clinics, multislice CT could offer a well suitable imaging alternative, but only if multiplanar reconstructions are performed consistently. Furthermore, radiology reports need to be improved by using more standardized assessment.",,"Gardeniers, M.;Wattjes, M. P.;Meulen, E. F.;Barkhof, F.;Bakker, J.",2016,Feb,10.1007/s12439-015-0154-0,0,
4251,Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study,"BACKGROUND: White-matter hyperintensities are commonly found on magnetic resonance imaging (MRI) of elderly people with or without dementia. Studies of the relation between severity of white-matter hyperintensities and cognitive impairment have had conflicting results. We undertook a longitudinal study of age-related decline in intellectual function and MRI at age 80 years. METHODS: From a cohort of 698 people born in 1914 and living in seven municipalities in Denmark, 68 healthy non-demented individuals had been tested with the Wechsler adult intelligence scale (WAIS) at ages 50, 60, and 70, and they agreed to further WAIS testing at age 80, and cerebral MRI at age 80-82 (mean age 82.3 years). We scored separately the numbers of periventricular and deep white-matter hyperintensities. FINDINGS: Scores for periventricular hyperintensities in this sample included all possible degrees of severity, but no participant scored more than 75% of maximum for deep white-matter hyperintensities. Neither type was related to the WAIS IQs of the 80-year assessment, but both were significantly associated with decline in performance IQ from age 50 to age 80 years (bivariate correlation coefficients 0.32, p=0.0087, and 0.28, p=0.0227, respectively). An analysis based on two WAIS subtests showed that the association between white-matter hyperintensities and cognitive impairment was significant only for cognitive decline in the decade 70-80 years. INTERPRETATION: Both periventricular and deep white-matter hyperintensities are related to decline in intelligence but, in healthy octogenarians, the cumulative effect of these features alone explains only a small part of the large differences among individuals in age-related decline in intelligence. Interpretation of the presence and severity of white-matter hyperintensities in a diagnostic context must be done cautiously.","Aged;Aged, 80 and over;Aging/ pathology;Brain/ pathology;Cerebral Ventricles/pathology;Cognition Disorders/ diagnosis/pathology;Cohort Studies;Demography;Female;Humans;Intelligence;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Regression Analysis;Wechsler Scales","Garde, E.;Mortensen, E. L.;Krabbe, K.;Rostrup, E.;Larsson, H. B.",2000,Aug 19,10.1016/s0140-6736(00)02604-0,0,
4252,Decline in intelligence is associated with progression in white matter hyperintensity volume,"OBJECTIVES: To quantify the time course of white matter hyperintensities (WMH) and assess the association between progression and cognitive decline in non-demented octogenarians. METHODS: From a Danish cohort of 698 people born in 1914, 26 participated in neuropsychological assessment (Wechsler adult intelligence scale) initiated at age 50, including cognitive testing and cerebral magnetic resonance imaging at the 80 and 85 year studies. WMH volumes were quantified and partial correlations were calculated between WMH volume change and decline in WAIS scores from 80 to 85. RESULTS: Progression in WMH volume ranged from 0 ml to 20.7 ml, providing a median increase of 2.6 ml (range 0.1 to 20.7, p<0.001) and, with a mean time interval between scans of 3.8 years, a rate of progression of 0.63 (0 to 6.8) ml/year. WMH volume measures for the two hemispheres were highly correlated (r = 0.95) and did not differ significantly. Increase in WMH volume was correlated with a simultaneous decline in verbal IQ (r = -0.65, p = 0.001), while baseline WMH was associated with subsequent decline in performance subtests (digit symbol, r = -0.57, p = 0.02). CONCLUSIONS: The association between WMH and decline in essential cognitive abilities even in well preserved elderly people suggests that WMH should be regarded as a risk factor for cognitive impairment and dementia.","Aged;Aged, 80 and over;Brain/ pathology;Cognition Disorders/ etiology;Cohort Studies;Dementia/etiology;Disease Progression;Female;Humans;Intelligence Tests;Magnetic Resonance Imaging;Male;Risk Factors","Garde, E.;Lykke Mortensen, E.;Rostrup, E.;Paulson, O. B.",2005,Sep,10.1136/jnnp.2004.055905,0,
4253,White matter alterations associated with chromosomal disorders,"White matter alterations in chromosomal disorders have been reported mainly in 18q-syndrome. Our aim was to evaluate white matter alterations in patients with chromosomal abnormalities detected through conventional cytogenetic techniques. Forty-four patients with chromosomal abnormalities, excluding trisomy 21, were diagnosed in our hospital between May 1999 and December 2002 (24 males, 20 females; mean age 6 years 4 months [SD 3 years 2 months], range 0 to 18 years). Of the 44 patients, 14 had brain magnetic resonance imaging (12 males, 2 females; mean age 4 years 2 months [SD 4 years 4 months]; five with sex chromosomal disorders [SCD] and nine with autosomal chromosomal disorders [ACD]). Of these 14 patients, eight (four with SCD and four with ACD) had abnormal white matter findings of similar patterns. These patients had pseudonodular, subcortical, and periventricular white matter high signal intensity images in T(2), and fluid-attenuated inversion recovery sequences that were isolated or confluent. The images did not correlate with the neurological clinical state. Given that eight of the 14 patients showed these lesions, their prevalence in different chromosomal abnormalities appears to be high, even though they have not been well reported in the literature. To our knowledge, these alterations have never been described in SCD. We concluded that unknown factors related to the myelination processes may be localized in different chromosomes.",,"García-Cazorla, A.;Sans, A.;Baquero, M.;García-Bargo, M. D.;Arellano, M.;Poo, P.;Gean, E.;Campistol, J.",2004,March,,0,
4254,Thalamic dementia secondary to acute bilateral paramedian thalamic infarcts after occlusion of the artery of Percheron,"Introduction. The anterior and medial part of the thalamus is the responsible of multiples cognitive functions through the thalamus-cortical connections. A bilateral thalamic infarction can cause a secondary dementia and these are related to a thalamocortical deafferentation with a partial recovery. We report a case of sudden onset dementia caused by bilateral thalamus lesions. Case report. A 42 smoker male, that suddenly had an acute confusional syndrome with altered language, bradypsychia, right hemiparesis and right hemisensory loss. Cranial magnetic resonance imaging showed a bilateral thalamic stroke probably due to a variant talamus irrigation (artery of Percheron type 2). From this date, in three months, the patient had attention deficit, impairment of memory retention, apathy, initiative deficit, depressive syndrome and mood changes. All these symptoms improving partially in the following six months. Conclusions. The thalamic stroke can cause a thalamic dementia, commonly bilateral and preferable located in the anterior and medial nuclei. In our case, cranial SPECT showed frontal hypocaptation for diaschisis phenomenon. © 2008, Revista de Neurología.",,"García-Casares, N.;Garzón-Maldonado, F. J.;De La Cruz-Cosme, C.",2008,February,,0,
4255,Cognitive impairment and dementia after intracerebral hemorrhage: A cross-sectional study of a hospital-based series,"Background: Frequencies of cognitive impairment and dementia have not been assessed in spontaneous intracerebral hemorrhage (ICH). The objective of this study was to determine the frequencies and patterns of cognitive impairment and dementia in a cross-sectional study of consecutive patients hospitalized in a single university medical center. Methods: Of 183 consecutive patients hospitalized between 2002 and 2006, 80 survivors were contacted and 78 were included (mean time since stroke 40 months). Thirty patients were scored with the Informant Questionnaire on Cognitive Decline in the Elderly and Instrumental Activities of Daily Living in a telephone interview, and 48 underwent a comprehensive clinical and neuropsychological assessment. Results: Dementia was observed in 18 of 78 patients (23%; 95% confidence interval [CI] 13-32%) and cognitive impairment without dementia was seen in 37 of 48 patients (77%; 95% CI 65-89%). The cognitive disorders mainly concerned episodic memory (52%), psychomotor speed (44%), and executive function (37%), followed by language and visuoconstructive abilities. In a logistic regression analysis, Rankin score >1 at discharge and hemorrhage volume were the initial factors to be selected as a predictor of long-term dementia. Conclusions: This single-center, cross-sectional study revealed that the prevalence of dementia and cognitive impairment without dementia after ICH are high and are similar to those observed in cerebral infarct. Further longitudinal, prospective studies are required to assess accurately the prevalence, mechanisms and predictors of post-ICH dementia. © 2013 by National Stroke Association.",adult;article;brain hemorrhage;clinical assessment;cognitive defect;computer assisted tomography;cross-sectional study;dementia;episodic memory;executive function;female;human;Informant Questionnaire on Cognitive Decline in the Elderly;Instrumental Activities of Daily Living;interview;language;major clinical study;male;neuropsychological test;nuclear magnetic resonance imaging;priority journal;psychomotor performance;questionnaire;Rankin scale,"Garcia, P. Y.;Roussel, M.;Bugnicourt, J. M.;Lamy, C.;Canaple, S.;Peltier, J.;Loas, G.;Deramond, H.;Godefroy, O.",2013,,,0,
4256,Spontaneous convexity subarachnoid haemorrhage: Clinical series of 3 patients with associated cerebral amyloid angiopathy,"Introduction Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment. Patients Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography. Results Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued. Conclusions We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.",amyloid beta protein;corticosteroid;levetiracetam;prednisone;tau protein;adult;aged;article;brain tomography;case report;cerebrospinal fluid;convexity subarachnoid hemorrhage;corticosteroid therapy;disease association;drug withdrawal;dysarthria;female;focal epilepsy;hemosiderosis;human;male;meninx;middle aged;neuroimaging;nuclear magnetic resonance imaging;protein phosphorylation;subarachnoid hemorrhage;vascular amyloidosis;x-ray computed tomography,"García Estévez, D. A.;García-Dorrego, R. M.;Nieto-Baltar, B.;Marey-Garrido, M.;Hierro-Torner, T.",2017,,10.1016/j.nrl.2015.11.004,0,
4257,,"Introduction: Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment. Patients: Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography. Results: Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued. Conclusions: We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.",aged;aneurysm;atrophy;case report;case study;clinical trial;computer assisted tomography;corticosteroid therapy;dementia;dysarthria;dysphasia;female;gene expression;headache;hemosiderosis;hippocampus;human;magnetic resonance angiography;male;medial temporal lobe;meninx;motor dysfunction;Priabonian;seizure;subarachnoid hemorrhage;symptom;syndrome;vascular amyloidosis;amyloid beta protein;etiracetam;prednisone;tau protein,"García Estévez, D. A.;García-Dorrego, R. M.;Nieto-Baltar, B.;Marey-Garrido, M.;Hierro-Torner, T.",2015,,,0,
4258,Spontaneous convexity subarachnoid haemorrhage: Clinical series of 3 patients with associated cerebral amyloid angiopathy Hemorragia subaracnoidea espontanea de la convexidad cerebral: una serie clinica de 3 pacientes asociada con angiopatia amiloide cerebral,"INTRODUCTION: Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment. PATIENTS: Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography. RESULTS: Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued. CONCLUSIONS: We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.",Apolipoprotein E;Apolipoproteina E;Beta-amyloid peptide;Cheiro-oral symptoms;Hemorragia subaracnoidea;Hemosiderosis meningea;Meningeal haemosiderosis;Microbleeds;Microsangrados;Peptido beta-amiloide;Subarachnoid haemorrhage;Sintomas queiroorales,"Garcia Estevez, D. A.;Garcia-Dorrego, R. M.;Nieto-Baltar, B.;Marey-Garrido, M.;Hierro-Torner, T.",2016,Jan 06,,0,
4259,Spontaneous convexity subarachnoid haemorrhage: Clinical series of 3 patients with associated cerebral amyloid angiopathy,"INTRODUCTION: Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment. PATIENTS: Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography. RESULTS: Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued. CONCLUSIONS: We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.",Apolipoprotein E;Apolipoproteina E;Beta-amyloid peptide;Cheiro-oral symptoms;Hemorragia subaracnoidea;Hemosiderosis meningea;Meningeal haemosiderosis;Microbleeds;Microsangrados;Peptido beta-amiloide;Subarachnoid haemorrhage;Sintomas queiroorales,"Garcia Estevez, D. A.;Garcia-Dorrego, R. M.;Nieto-Baltar, B.;Marey-Garrido, M.;Hierro-Torner, T.",2016,Jan 6,10.1016/j.nrl.2015.11.004,0,
4260,[Use of 99mTc-HMPAO SPECT in the study of AIDS-correlated dementia] Impiego della SPECT con 99mTc-HMPAO nello studio della demenza AIDS correlata,"AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, grey and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc 99m HMPAO has proved to be an useful tool in studying Alzheimer and multi-infarct dementia, and its use has been recently proposed in AIDS-dementia. We studied with Tc 99m HMPAO 57 Pts (11 HIV+, 26 ARC, 17 AIDS) and control group of 7 drug-addicted seronegative Pts. We found positive results in 45% SPECT, 18% CT, 0% neurological tests of dementia in HIV+ phase, versus 52%, 41, 20% in ARC phase and 94%, 88% and 76% in AIDS phase, while all control Pts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99 mTc HMPAO has an important role in assessing CBF changes in earlier stages of AIDS disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease.","0 (Organotechnetium Compounds);0 (Oximes);3B744AG22N (Technetium Tc 99m Exametazime);AIDS Dementia Complex/ diagnostic imaging;Adult;Brain/ diagnostic imaging;Female;Humans;Male;Middle Aged;Organotechnetium Compounds;Oximes;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Garavelli, P. L.;Zoccola, R.;Villa, G.;Scopinaro, G.",1992,Jun,,0,
4261,[Use of 99mTc-HMPAO SPECT in the study of AIDS-correlated dementia],"AIDS dementia complex is a well-defined neurological manifestation of the HIV infection. Its anatomo-pathological pattern is cerebral atrophy, grey and white matter abnormalities and vascular changes, and the main symptom is progressive dementia. SPECT with Tc 99m HMPAO has proved to be an useful tool in studying Alzheimer and multi-infarct dementia, and its use has been recently proposed in AIDS-dementia. We studied with Tc 99m HMPAO 57 Pts (11 HIV+, 26 ARC, 17 AIDS) and control group of 7 drug-addicted seronegative Pts. We found positive results in 45% SPECT, 18% CT, 0% neurological tests of dementia in HIV+ phase, versus 52%, 41, 20% in ARC phase and 94%, 88% and 76% in AIDS phase, while all control Pts were negative. Control group is too small to exclude with all possibility of doubt cerebral blood flow impairment caused by drug damage but nevertheless we think that SPECT examination with 99 mTc HMPAO has an important role in assessing CBF changes in earlier stages of AIDS disease. These changes are probably forerunners of definitive cerebral damage and may be important markers of the advancement of disease.","AIDS Dementia Complex/*radionuclide imaging;Adult;Brain/*radionuclide imaging;Female;Humans;Male;Middle Aged;Organotechnetium Compounds;Oximes;Technetium Tc 99m Exametazime;*Tomography, Emission-Computed, Single-Photon","Garavelli, P. L.;Zoccola, R.;Villa, G.;Scopinaro, G.",1992,Jun,,0,
4262,Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's disease and vascular dementia assessed by arterial spinlabeling magnetic resonance imaging,"Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.","Aged;Aged, 80 and over;Alzheimer Disease/ physiopathology/radionuclide imaging;Arteries/ physiopathology/radionuclide imaging;Brain/ blood supply/physiopathology/radionuclide imaging;Cerebrovascular Circulation/ physiology;Dementia, Vascular/ physiopathology/radionuclide imaging;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/radionuclide imaging;Spin Labels","Gao, Y. Z.;Zhang, J. J.;Liu, H.;Wu, G. Y.;Xiong, L.;Shu, M.",2013,Feb,,0,
4263,Changes of brain structure in Parkinson's disease patients with mild cognitive impairment analyzed via VBM technology,"OBJECTIVE: To analyze changes in cerebral grey matter volume and white matter density in non-dementia Parkinson's disease patients using voxel-based morphometry (VBM) technology; to investigate features of brain structure changes in Parkinson's disease patients with mild cognitive impairment (PD-MCI), and reveal their intrinsic pathological changes. METHODS: Based on the diagnostic criteria of PD-MCI, 23 PD-MCI patients, 23 Parkinson's disease patients with normal cognition (PD-NC), and 21 age- and gender-matched healthy people were recruited for the study. Scans were performed on all subjects on a 3.0T MR scanner to obtain brain structural magnetic resonance images. Images were preprocessed using the VBM8 tool from SPM8 software package on the Matlab R2008a platform, and data were then analyzed using the SPM statistical software package to compare the differences of grey matter volume and white matter density between groups, and to evaluate the brain structural changes corresponding to the overall cognitive function. RESULTS: Compared to the control group, the PD-NC group suffered from grey matter atrophy, mainly found in the prefrontal lobe, limbic lobe and left temporal gyrus. The PD-MCI group suffered from grey matter atrophy found in the frontal lobe, limbic lobe, basal ganglia and cerebellum. Compared to the PD-NC group, the PD-MCI group suffered from grey matter atrophy found in the left-side middle temporal gyrus, inferior temporal gyrus and frontal lobe. The grey matter regions correlated with MMSE score (mainly memory related) including the right cingulate gyrus and the limbic lobe. The grey matter regions correlated with MoCA score (mainly non-memory related) including the frontal lobe, basal ganglia, parahippocampal gyrus, occipital lobe and the cerebellum. Additionally, overall cognitive function in non-dementia PD was mainly located in the frontal and limbic system, and was dominated by subcortical atrophy. CONCLUSION: Structural changes in PD-MCI patients are associated with overall cognitive function, and the atrophic areas are mainly located in the frontal and limbic system, and are dominated by subcortical atrophy. Moreover, atrophy of limbic lobes is associated with impaired memory, whereas frontal lobe atrophy is associated with executive dysfunction. In addition, the subtle brain structure of the PD early cognitive impairment stage and PD-MCI stage can be detected via VBM technology, and thus, local brain atrophy may be a neuroimaging marker for the early diagnosis of PD-MCI.",Mmse;Mri;Mild cognitive impairment;MoCA;Parkinson's disease;Voxel-based morphometry,"Gao, Y.;Nie, K.;Huang, B.;Mei, M.;Guo, M.;Xie, S.;Huang, Z.;Wang, L.;Zhao, J.;Zhang, Y.;Wang, L.",2017,Sep 29,,0,
4264,Brain iron deposition analysis using susceptibility weighted imaging and its association with body iron level in patients with mild cognitive impairment,"The aim of the present study was to analyze brain and body iron levels among patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and normal controls (NCs). A total of 90 participants (30 MCI, 30 AD, 30 NC) were enrolled. Brain iron content was quantified using susceptibility weighted imaging (SWI). Phase values were used to calculate bilateral iron content in the hippocampus (HP), substantia nigra, red nucleus (RN), dentate nucleus (DN), caudate nucleus (CN), globus pallidus (GP), putamen (PUT), frontal white matter, temporal cortex (TC), and parietal cortex. Body iron indices, including serum iron, serum transferrin, ferritin and total iron binding capacity, were measured. Phase values of the left (L)DN, LCN, and bilateral PUT in the MCI group were significantly lower compared with NC group. Phase values of the right (R)RN, bilateral DN, and bilateral PUT in the AD group were significantly lower compared with the MCI group. Phase values of the bilateral HP, DN, RN, CN, GP, PUT, and LTC in the AD group were significantly lower compared with the NC group. Serum ferritin levels in the MCI and AD groups were significantly lower compared with the NC group. Only serum iron in the AD group was positively associated with iron content in the RHP. Brain iron deposition and body iron levels both increased in MCI and AD patients, however, excessive brain iron accumulation may have no association with body iron level. SWI was particularly effective at recognizing the presence of brain iron in the MCI and AD groups.",,"Gao, L.;Jiang, Z.;Cai, Z.;Cai, M.;Zhang, Q.;Ma, Y.;Li, G.;Zhao, F.;Ma, Q.",2017,Dec,,0,
4265,Possible retrogenesis observed with fiber tracking: an anteroposterior pattern of white matter disintegrity in normal aging and Alzheimer's disease,"Retrogenesis refers to the phenomenon by which degenerative processes in aging reverse the sequence of acquisition in development. Although there has been some evidence for brain retrogenesis in abnormal aging, e.g., Alzheimer's disease (AD), it has not been explicitly addressed in the normal aging. Using diffusion tensor imaging and tractography, we explored the effects of normal and abnormal aging on the integrity of white matter (WM) in fifty participants, including 18 AD patients, 17 normal elderly, and 15 normal young adults. Compared with young adults, the traditional voxel-based analysis, and the quantitative fiber tracking methods revealed lower fractional anisotrophy (FA) for both normal elderly and AD patients, indicating WM disintegrity in the anterior part of the brain with developmentally late-myelinating fiber bundles. Furthermore, AD patients showed lower FA in the posterior part of the brain with relatively early-myelinating fiber bundles. Additional analysis on axial diffusion and radial diffusion measures suggest that demyelination may be the main mechanism underlying the observed microstructural impairments. Consistent with a proposal of retrogenesis, our results demonstrate an anteroposterior pattern of white matter disintegrity in both normal aging and AD, with the pattern being more salient in the latter than in the former.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Analysis of Variance;Anisotropy;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging/methods;Female;Humans;Imaging, Three-Dimensional/methods;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Young Adult","Gao, J.;Cheung, R. T.;Lee, T. M.;Chu, L. W.;Chan, Y. S.;Mak, H. K.;Zhang, J. X.;Qiu, D.;Fung, G.;Cheung, C.",2011,,10.3233/jad-2011-101788,0,
4266,Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook dementia study,"Purpose: Quantification methods for white matter hyperintensities (WMH) on Magnetic Resonance Imaging are heterogeneous, deterring their application. This study compared three WMH rating scales, varying in complexity, and a volumetric method, to evaluate trade-offs between complexity and clinical utility in differentiating dementia subgroups and in correlating with cognition. Methods: WMH were rated using the Fazekas, Age-Related White Matter Changes (ARWMC) and Scheltens scales, and segmented by computational volumetry in 108 patients with Alzheimers Disease (AD), 23 with Mild Cognitive Impairment (MCI) and 34 normal controls (NC). Global and hippocampal atrophy, age and education, were accounted for in correlations of WMH with cognitive domains. Results: Intra- and inter-rater reliability were high (intraclass correlation coefficients = 0.88-0.97) across rating scales. WMH scores of all scales were highly correlated with volumes (Spearman r = 0.78-0.90, Ps < 0.001), as well as with each other (Spearman r = 0.86-0.91, Ps < 0.001). The Fazekas scale showed significant separation between AD, MCI and NC using non-parametric analysis, while the ARWMC and Scheltens scales, and WMH volumes demonstrated significant correlations (standardized β = -0.19 to -0.24, Ps < 0.05) with cognitive domain scores using multivariate regression analysis, controlling for age, education, global and hippocampal atrophy in patients with AD. Conclusions: This study suggests that the degree of complexity of WMH rating scales did not affect validation against WMH volumes, but did vary in validation against cognition. The simplest scale performed best in separating cognitive subgroups, but the more complex scales and quantification correlated better with cognitive measures, especially executive function. Hence the best choice of scale depends on the particular application. © 2011 IOS Press and the authors. All rights reserved.",Age Related White Matter Changes scale;aged;aging;article;brain atrophy;brain size;cognition;controlled study;correlation analysis;dementia;Fazekas scale;female;hippocampus;human;interrater reliability;intrarater reliability;major clinical study;male;multivariate analysis;neuroimaging;nuclear magnetic resonance imaging;priority journal;radiological parameters;rating scale;Scheltens scale;validity;white matter;white matter hyperintensity;Signa,"Gao, F. Q.;Swartz, R. H.;Scheltens, P.;Leibovitch, F. S.;Kiss, A.;Honjo, K.;Black, S. E.",2011,,10.3233/jad-2011-0058,0,4267
4267,Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the sunnybrook dementia study,"Purpose: Quantification methods for white matter hyperintensities (WMH) on Magnetic Resonance Imaging are heterogeneous, deterring their application. This study compared three WMH rating scales, varying in complexity, and a volumetric method, to evaluate trade-offs between complexity and clinical utility in differentiating dementia subgroups and in correlating with cognition. Methods: WMH were rated using the Fazekas, Age-Related White Matter Changes (ARWMC) and Scheltens scales, and segmented by computational volumetry in 108 patients with Alzheimer's Disease (AD), 23 with Mild Cognitive Impairment (MCI) and 34 normal controls (NC). Global and hippocampal atrophy, age and education, were accounted for in correlations of WMH with cognitive domains. Results: Intra-and inter-rater reliability were high (intraclass correlation coefficients = 0.88-0.97) across rating scales. WMH scores of all scales were highly correlated with volumes (Spearman r = 0.78-0.90, Ps < 0.001), as well as with each other (Spearman r = 0.86-0.91, Ps < 0.001). The Fazekas scale showed significant separation between AD, MCI and NC using non-parametric analysis, while the ARWMC and Scheltens' scales, and WMH volumes demonstrated significant correlations (standardized β =-0.19 to-0.24, Ps < 0.05) with cognitive domain scores using multivariate regression analysis, controlling for age, education, global and hippocampal atrophy in patients with AD. Conclusions: This study suggests that the degree of complexity of WMH rating scales did not affect validation against WMH volumes, but did vary in validation against cognition. The simplest scale performed best in separating cognitive subgroups, but the more complex scales and quantification correlated better with cognitive measures, especially executive function. Hence the best choice of scale depends on the particular application. © 2011 The authors and IOS Press. All rights reserved.",,"Gao, F. Q.;Swartz, R. H.;Scheltens, P.;Leibovitch, F. S.;Kiss, A.;Honjo, K.;Black, S. E.",2011,2011,,0,
4268,Is encroachment of the carotid termination into the substantia innominata associated with its atrophy and cognition in Alzheimer's disease?,"The internal carotid artery termination (CAT) ends in a T-shaped bifurcation just below the substantia innominata (SI), which contains cognitively strategic cholinergic neurons and undergoes atrophy in Alzheimer's disease (AD). This study investigated whether an elongated CAT with possible resulting encroachment into the SI would correlate with SI atrophy and with cognitive dysfunction in AD. We rated the degree of CAT encroachment upon the SI and measured SI volume on magnetic resonance imaging in 30 AD patients, 30 AD patients with subcortical small vessel disease, and 30 age-matched controls. CAT encroachment significantly correlated with SI volume after adjusting for age within the overall group and the groups with dementia. AD patients with higher CAT encroachment scores had lower SI volumes and lower attention, memory, and executive test scores. These data suggest that CAT encroachment may mechanically injure the SI, exacerbating cholinergic damage and contributing to cognitive impairment. This process may represent a possible previously underappreciated mechanism for interaction between large-vessel cerebrovascular disease and AD.","Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/ pathology;Atrophy/pathology;Carotid Artery, Internal/ pathology;Cognition Disorders/epidemiology/ pathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Substantia Innominata/ pathology","Gao, F. Q.;Pettersen, J. A.;Bocti, C.;Nestor, S. M.;Kiss, A.;Black, S. E.",2013,Jul,10.1016/j.neurobiolaging.2013.01.009,0,
4269,Radial contrast enhancement on brain magnetic resonance imaging diagnostic of primary angiitis of the central nervous system: A case report and review of the literature,"Introduction. Primary angiitis of the central nervous system is a rare disease of unclear etiology. There is no single test diagnostic of primary angiitis of the central nervous system. We report an unusual pattern on brain magnetic resonance imaging that might be specific for primary angiitis of the central nervous system. Case presentation. A 47-year-old Caucasian man developed progressive bilateral hand tremor, difficulty walking, cognitive slowing and headache. A physical examination showed bilateral hand tremor with dysmetria, hyperreflexia and abnormal gait. Magnetic resonance imaging of his brain showed bilateral, symmetrical, increased intensity on T2-weighted images concurrent with linear contrast enhancement in a radial distribution throughout his white matter, sparing subcortical regions in his centrum semiovale, corona radiata, basal ganglia and brainstem. Magnetic resonance spectroscopy demonstrated elevated choline and decreased N-acetyl aspartate. Except for elevated protein and lymphocytic pleocytosis, examination of his cerebrospinal fluid showed no abnormalities. Serological tests for rheumatologic, vasculitic, paraneoplastic, infectious and peroxisomal disorders were negative. A brain biopsy revealed primary angiitis of the central nervous system. Our patient was treated with steroids and intravenous cyclophosphamide, with improvement in signs and symptoms as well as changes on magnetic resonance imaging. Conclusion: Bilateral, symmetrical, increased intensity on T2-weighted images concurrent with linear contrast enhancement in a radial distribution throughout the white matter on magnetic resonance imaging of the brain should be recognized as a feature of primary angiitis of the central nervous system, and might avoid the need for a brain biopsy to diagnose primary angiitis of the central nervous system. © 2014 Ganta et al.; licensee BioMed Central Ltd.",,"Ganta, K.;Malik, A. M.;Wood, J. B.;Levin, M. C.",2014,,,0,
4270,Adult-onset adrenoleukodystrophy presenting as a psychiatric disorder: MRI findings,"A 35-year-old, previously healthy man presented psychiatric symptoms lasting four years, receiving treatment with neuroleptics. One year later he evolved with gait disequilibrium. After a further six months, cognitive symptoms were characterized with rapid evolution to a profound demented state. MRI showed signal changes in cerebral white matter and very long-chain fatty acids were detected in blood.",adult-onset adrenoleukodystrophy;leukodystrophies;leukoencephalopathies;magnetic resonance imaging,"Galvao, A. C. R.;Machado-Porto, G. C. L.;Porto, F. H. G.;Lucato, L. T.;Nitrini, R.",2012,Oct-Dec,,0,
4271,Contribution of computerized tomography and nuclear magnetic resonance to the diagnosis of vascular dementia,"Nuclear magnetic resonance (NMR) and computerized tomography (CT) have become indispensable to the exploration of patients with vascular dementia. NMR is remarkable for its innocuity, its anatomical accuracy, its sensitivity and the three-dimensional approach it offers. CT is less sensitive, but the examinations are shorter and less costly. These two techniques seem to be about equally effective in visualizing multiple infarcts, although NMR gives a better contrast. In dementia due to multiple infarcts, the bilateral cortical and subcortical lesions coexist with moderate cortical trophy. The cerebral lacunae of lacunar dementia are better visualized by NMR; they are distributed on both sides, predominate in the frontal lobes and only produce slight cortical atrophy, less pronounced than ventricular dilatation. The main advantage of NMR is its high sensitivity in detecting early changes in the white matter, changes which are particularly perceptible in juxta- and periventricular areas in arteriosclerosis subcortical leucoencephalopathy. NMR, not very specific here, does not readily differentiate these lesions from those of other types of leucoencephalopathy. The finding of hypodense areas at CT or of hypersignals at NMR (T2) around the ventricles may help in differentiating between vascular dementia, irrespective of its mechanism, and primary dementia.",age;brain infarction;central nervous system;clinical article;computer assisted tomography;dementia;diagnosis;etiology;human;nuclear magnetic resonance;peripheral vascular system;priority journal;cerebrovascular accident,"Gallois, Ph;Pruvo, J. P.",1987,,,0,
4272,White matter damage in primary progressive aphasias: a diffusion tensor tractography study,"Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.","Aged;Aphasia, Primary Progressive/ pathology/psychology;Atrophy;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Nerve Net/ pathology;Neuropsychological Tests","Galantucci, S.;Tartaglia, M. C.;Wilson, S. M.;Henry, M. L.;Filippi, M.;Agosta, F.;Dronkers, N. F.;Henry, R. G.;Ogar, J. M.;Miller, B. L.;Gorno-Tempini, M. L.",2011,Oct,10.1093/brain/awr099,0,
4273,MR spectroscopic pulvinar sign in a case of variant Creutzfeldt-Jakob disease,"We report MR spectroscopic findings in a patient hospitalized with biopsy-proven variant Creutzfeldt-Jakob (vCJD) disease. N-acetyl aspartate was markedly decreased in the postero-medial part of the thalami (pulvinar) but was not diminished in the parieto-occipital white matter and cortical grey matter. These observations, which are in accordance with the pathological findings in this disease, suggest that MR spectroscopy, a highly sensitive method for the detection of subtle brain metabolic dysfunction, could be of interest for the diagnosis, prognosis and therapeutic follow-up of vCJD.",adult;article;brain biopsy;case report;Creutzfeldt Jakob disease;electroencephalogram;female;human;neurologic disease;neuroradiology;nuclear magnetic resonance imaging;pulvinar;thalamus,"Galanaud, D.;Dormont, D.;Grabli, D.;Charles, P.;Hauw, J. J.;Lubetzki, C.;Brandel, J. P.;Marsault, C.;Cozzone, P. J.",2002,,,0,
4274,The role of brain infarcts and hippocampal atrophy in subcortical ischaemic vascular dementia,"We investigated if, in patients with vascular lesions, the variable that best discriminated demented from non-demented patients was the severity of the vascular pathology or the degree of hippocampal atrophy. A total of 39 patients multiple subcortical infarcts, who could be considered as possible vascular dementia with small vessel pathology, with underwent a neuropsychological study and brain magnetic resonance imaging (MRI) DSM IV criteria supported by neuropsychological data were used to distinguish demented from non-demented patients. The MRI study took into account the degree of hippocampal atrophy (hippocampal height and interuncal distance) and the severity of vascular pathology (number of brain infarcts). The distribution of lesions and a factor analysis showed that hippocampal atrophy is a better predictor of dementia than the number of brain infarcts. Multiple subcortical infarcts alone are probably not able to cause clinical dementia but the presence of vascular lesions increases the expression of concomitant Alzheimer's disease.","Aged;Alzheimer Disease/etiology/pathology/psychology;Atrophy/ pathology/physiopathology/psychology;Brain Ischemia/ pathology/physiopathology/psychology;Cerebral Arteries/pathology/physiopathology;Cerebral Infarction/ pathology/physiopathology/psychology;Dementia, Vascular/etiology/ pathology/ psychology;Diagnosis, Differential;Disease Progression;Female;Hippocampus/ pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests","Gainotti, G.;Acciarri, A.;Bizzarro, A.;Marra, C.;Masullo, C.;Misciagna, S.;Tartaglione, T.;Valenza, A.;Colosimo, C.",2004,Oct,10.1007/s10072-004-0321-5,0,
4275,Cerebrotendinous xanthomatosis: Neuroimaging findings in two siblings from an Indian family,"Cerebrotendinous xanthomatosis (CTX) is exceptionally rare in the Indian population. We present and discuss the clinical, radiological and histopathologic findings in 2 siblings with CTX. Both the patients had juvenile cataract, mental retardation and marked cerebellar ataxia. The Achilles tendon swelling was present in only 1 patient (Case 2). MR imaging showed typical bilateral and symmetrical involvement of the dentate nuclei, inferior olives, brainstem and cerebellar hemispheric white matter. Although the diagnosis of CTX was made in the 3rd decade in both our cases, early diagnosis is possible if neuroimaging is done in the early course of the disease.",,"Gaikwad, S. B.;Garg, A.;Mishra, N. K.;Gupta, V.;Srivastava, A.;Sarkar, C.",2003,September,,0,
4276,Brain parenchymal density measurements by CT in demented subjects and normal controls,"Parenchymal density measurements of 14 regions of gray and white matter from each cerebral hemisphere were made from CT scans of 25 subjects who had varying degrees of dementia as measured by a global Clinical Dementia Rating, and also from CT scans of 33 normal control subjects. There were few significant differences between the two groups in the mean density value for each of the regions examined, although several individual psychometric tests did correlate with density changes. Moreover, for six regions in the cerebral cortex, and for one region in the thalamus of each hemisphere, we found no significant correlation between the gray-white matter density difference and dementia. There was, however, a loss of the discriminability between the gray and white matter with an increase in the size of the ventricles. These findings may be attributed to the loss of white matter volume.","Aged;Alzheimer Disease/pathology/psychology/*radiography;Brain/pathology/*radiography;Cerebral Cortex/radiography;Dementia/*radiography;Densitometry;Female;Humans;Male;Psychological Tests;Thalamus/radiography;*Tomography, X-Ray Computed","Gado, M.;Danziger, W. L.;Chi, D.;Hughes, C. P.;Coben, L. A.",1983,Jun,10.1148/radiology.147.3.6844607,0,
4277,Leukoencephalopathy following chemotherapy for rhabdomyosarcoma: reversibility of cerebral changes demonstrated by computed tomography,"Neurotoxicity in the form of leukoencephalopathy has been recognized with increasing frequency as a complication of the treatment of childhood malignancies. Confusion, somnolence ataxia, spasticity, seizures, and occasional progression to dementia, coma, and death characterise the clinical syndrome. Pathologically, multifocal necrosis has been observed in the cerebral white matter. The diagnosis has been made at autopsy and by brain biopsy. The authors report a child who slowly developed dementia and poor motor function while receiving intraventricular chemotherapy and in whom computed tomography was instrumental in diagnosing and following the course of leukoencephalopathy.",cyclophosphamide;cytarabine;dactinomycin;hydrocortisone;methotrexate;semustine;vincristine;adverse drug reaction;cancer chemotherapy;child;clinical study;computer assisted tomography;dementia;drug therapy;intrathecal drug administration;leukoencephalitis;leukoencephalopathy;major clinical study;neurotoxicity;rhabdomyosarcoma;therapy,"Fusner, J. E.;Poplack, D. G.;Pizzo, P. A.;Di Chiro, G.",1977,,,0,
4278,Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis,"Background: Neuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation. Methods: Clinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC). Results: All MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure. Conclusions: This data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS. © SAGE Publications 2008.",,"Furby, J.;Hayton, T.;Anderson, V.;Altmann, D.;Brenner, R.;Chataway, J.;Hughes, R. A. C.;Smith, K. J.;Miller, D. H.;Kapoor, R.",2008,2008,,0,
4279,What is the relationship between type 2 diabetes mellitus status and the neuroradiological correlates of cerebral small vessel disease in adults? Protocol for a systematic review,"BACKGROUND: Cerebral small vessel disease (CSVD) is a common cause of stroke, dementia, and functional decline. In recent years, neuroradiologic correlates of CSVD have been identified. These imaging findings, best characterized on magnetic resonance imaging (MRI), include some combination of white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Though some cohorts have reported that participants with type 2 diabetes mellitus (T2DM), an important risk factor for CSVD, may have a distinct neuroradiologic phenotype, this relationship is not well-characterized. Adults with diabetes mellitus have a two- to threefold higher incidence of ischemic stroke compared to controls and are an increasingly important population given global trends of increasing diabetes prevalence. This study aims to determine if adults with CSVD and T2DM have a distinct neuroradiologic phenotype. METHODS: A systematic search of the literature will be conducted to find articles that report the MRI features of CSVD in a cohort of participants including those with and without type 2 diabetes mellitus (T2DM). A number of databases will be searched including MEDLINE, Embase, CINAHL, and Web of Science. Proceedings and abstracts from key conferences will also be reviewed and relevant journals hand searched for additional papers. The references from selected papers will be scanned. Screening of potential articles, data extraction, and quality appraisal will be performed in duplicate by independent reviewers. Odds ratios and 95% confidence intervals for the presence versus absence of each neuroradiologic correlate of interest from each included study will be calculated. If sufficient homogeneity exists among studies, a meta-analysis will be performed for each neuroradiologic correlate of CSVD. If heterogeneity of studies precludes data pooling, results will be presented in narrative form. DISCUSSION: Determining whether a distinct neuroradiologic phenotype of CSVD exists in adults with T2DM will provide insight into the underlying mechanisms of CSVD and guide future research on therapeutic targets. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016046669.",Cerebral microbleeds;Cerebral small vessel disease;Lacunes;Magnetic resonance imaging;Perivascular spaces;Stroke;Systematic review;Type 2 diabetes mellitus;White matter hyperintensities,"Funnell, C.;Doyle-Waters, M. M.;Yip, S.;Field, T.",2017,Jan 17,,0,
4280,[Nervous system manifestations in HIV infected children] Affektionen des Nervensystems bei perinatal HIV-infizierten Kindern,"In 34 perinatally HIV infected children time of manifestation, type and treatability of neurologic disorders were investigated for a period of 7 years (1987-1994). Neurological investigations were done every 6 months; EEG and MRI/CT were examined initially in the asymptomatic stage and were repeated when neurologic Symptoms occurred. Zidovudine therapy was started after onset of symptoms, dosage was raised, when treatment with Zidovudine had already begun (600-720 mg/m2/day). Various neurological manifestations were seen in 4 of 12 patients in stage B (33%) and in 11 of 14 children in AIDS (80%). 7 of the 14 AIDS-patients (50%) developed a subacute progressive course or progressive plateau course and 4 of 14 (30%) a static course of encephalopathy. Pathological changes in EEG were seen in 54% of investigated patients with neurological deficits. Neuroimaging revealed pathological findings in all symptomatic subjects, 6 of 11 patients in AIDS (55%) has a severe general cerebral atrophy and multifocal white matter lesions. Zidovudine had a positive temporary effect from 6 to 12 months in 5 of 11 treated patients (45%). At present a thorough neurological examination is the most sensitive method to detect neurological impairment in HIV infected children. In most cases CT/MRI scan provides information about the course of the encephalopathy. Antiretroviral therapy has a limited benefit, if neurologic symptoms start after the second year of life.","0 (Anti-HIV Agents);4B9XT59T7S (Zidovudine);AIDS Dementia Complex/ diagnosis/drug therapy;Anti-HIV Agents/administration & dosage;Brain/drug effects/pathology;Child;Child, Preschool;Dose-Response Relationship, Drug;Electroencephalography/drug effects;Female;HIV Infections/ congenital/diagnosis/drug therapy;Humans;Infant;Infant, Newborn;Magnetic Resonance Imaging;Male;Neurologic Examination/drug effects;Pregnancy;Tomography, X-Ray Computed;Zidovudine/administration & dosage","Funk, M.;Joseph-Steiner, J.;Hernaiz-Driever, P.;Mentzer, D.;Gohlich-Ratmann, G.;Bollinger, M.;Kreuz, W.;Kornhuber, B.;Jacobi, G.",1996,Sep-Oct,,0,
4281,[Nervous system manifestations in HIV infected children],"In 34 perinatally HIV infected children time of manifestation, type and treatability of neurologic disorders were investigated for a period of 7 years (1987-1994). Neurological investigations were done every 6 months; EEG and MRI/CT were examined initially in the asymptomatic stage and were repeated when neurologic Symptoms occurred. Zidovudine therapy was started after onset of symptoms, dosage was raised, when treatment with Zidovudine had already begun (600-720 mg/m2/day). Various neurological manifestations were seen in 4 of 12 patients in stage B (33%) and in 11 of 14 children in AIDS (80%). 7 of the 14 AIDS-patients (50%) developed a subacute progressive course or progressive plateau course and 4 of 14 (30%) a static course of encephalopathy. Pathological changes in EEG were seen in 54% of investigated patients with neurological deficits. Neuroimaging revealed pathological findings in all symptomatic subjects, 6 of 11 patients in AIDS (55%) has a severe general cerebral atrophy and multifocal white matter lesions. Zidovudine had a positive temporary effect from 6 to 12 months in 5 of 11 treated patients (45%). At present a thorough neurological examination is the most sensitive method to detect neurological impairment in HIV infected children. In most cases CT/MRI scan provides information about the course of the encephalopathy. Antiretroviral therapy has a limited benefit, if neurologic symptoms start after the second year of life.","AIDS Dementia Complex/*diagnosis/drug therapy;Anti-HIV Agents/administration & dosage;Brain/drug effects/pathology;Child;Child, Preschool;Dose-Response Relationship, Drug;Electroencephalography/drug effects;Female;HIV Infections/*congenital/diagnosis/drug therapy;Humans;Infant;Infant, Newborn;Magnetic Resonance Imaging;Male;Neurologic Examination/drug effects;Pregnancy;Tomography, X-Ray Computed;Zidovudine/administration & dosage","Funk, M.;Joseph-Steiner, J.;Hernaiz-Driever, P.;Mentzer, D.;Gohlich-Ratmann, G.;Bollinger, M.;Kreuz, W.;Kornhuber, B.;Jacobi, G.",1996,Sep-Oct,10.1055/s-2008-1046487,0,
4282,Magnetic resonance imaging cinecisternography in patients with white matter lesions,"1. The dynamic changes in ventricular size were computed by MRI cinecisternography. 2. The data analyzed showed that the phasic changes in size of the third ventricle and/or fourth ventricle were reduced in patients with the small multiple infarcts, with dementia, and with enlarged lateral ventricles when compared to subjects without these findings. 3. The derangement in CSF flow dynamics may be involved in the pathogenesis of vascular dementia.",,"Fukuuchi, Y.;Amano, T.;Shiga, H.;Ichijo, M.;Itoh, Y.;Gotoh, F.",1992,,10.1016/s1052-3057(10)80048-5,0,
4283,Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia,"A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using (123)I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hzθ waves on the background of α activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the (99)Gly←Asp and 409Thr←Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.",,"Fukutani, Y.;Noriki, Y.;Sasaki, K.;Isaki, K.;Kuriyama, M.;Kurosawa, K.;Ida, H.",1999,June,,0,
4284,Familial juvenile encephalopathy (Binswanger type) with alopecia and lumbago - A syndrome,"Familial cases of young-adult-onset Binswanger-type encephalopathy with alopecia and lumbago without hypertension are presented. Their paternal grandfarther and maternal grandmother were siblings. Case 1. A 34-year-old man started to have memory disturbance and lose his hair at about the age of 25. At the age of 30 he developed low back pain acutely and had an operation because the myelogram showed total block at Th12 suggesting spinal cord tumor. At exploration, however, only arachnoid adhesion was noted. Three months later he suffered from apoplexy resulting in right hemiparesis and dysarthria. At the age of 31 he became disturbed in swallowing. He was admitted to our hospital at the age of 33. Examination on admission revealed that he had alopecia, dementia, emotional incontinence and pseudobulbar palsy but no hypertension. The tendon reflexes were increased and bilateral Hoffmann signs and Babinski signs were noted. Laboratory data were normal apart from mildly high hematocrit. Ct scan revealed moderate brain atrophy and white matter low attenuation. Cerebral angiogram showed mild arteriosclerotic change in small arteries. A small artery found in the left quadriceps muscle biopsy specimen had prominent muscular hypertrophy. Case 2. This is a younger brother of case 1, who started to lose his hair since the age of 17. At the age of 21 he developed low back pain acutely and had an operation with the diagnosis of lumbar disk herniation because of total block at L3 on myelogram. At the age of 26 disturbance of gait and speech appeared insidiously. He visited our outpatient clinic at the age of 27. On examination he had mild alopecia, generalized hyperreflexia and slight dysarthria but the blood pressure was normal. CT scan revealed almost identical abnormalities to case 1. Case 3. This is the youngest brother. He started to lose his hair since the age of 17. At the age of 18 he had an episode of acute low back pain. He visited our out-patient clinic at the age of 26. On examination he had mild generalized hyperreflexia and the blood pressure was normal. CT scan revealed mild white matter low attenuation. We could find four similar cases only in Japanese literatures (Maeda et al., 1965, 1976; Nemoto, 1966; Kondo et al., 1970). All the seven cases are characterized to have familial juvenile Binswanger type encephalopathy associated with alopecia, lumbago and normal blood pressure. Cerebral arteriosclerosis and white matter damage were demonstrated radiologically or pathologically in all the cases. We propose that it is clinically a systemic syndrome although its pathogenesis is awaited for further research.",adult;age;alopecia;Binswanger encephalopathy;brain angiography;brain disease;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;etiology;familial disease;heredity;histology;human;low back pain;muscle;muscle biopsy;musculoskeletal system;peripheral vascular system,"Fukutake, T.;Hattori, T.;Kita, K.;Hirayama, K.",1985,,,0,
4285,Apraxia of tool use: An autopsy case of biparietal infarction,"Although disorders in the use of single objects have been reported, there have been few detailed analyses. We describe the autopsy case of a 65-year-old, right-handed male patient with severe impairment of actual tool use which was caused by biparietal infarctions. He persistently and stably showed a severely defective use of actual objects, single or multiple, and relatively well-preserved pantomimes of object use and intransitive gestures. He did not have aphasia or dementia, and his ability for tool naming and function description was completely preserved. The author identified similar patterns of errors about a tool-action(-target) relationship both in single-object use and multiple-object use. Lesion analysis showed cortical infarcts mainly located in the bilateral inferior parietal lobules, extending into the temporal lobe on the right side. Copyright © 2003 S. Karger AG, Basel.",aged;analytical error;aphasia;apraxia;article;autopsy;brain infarction;case report;dementia;disease course;gesture;human;human tissue;male;neurologic examination;neuropsychological test;parietal lobe;priority journal;right handedness;task performance;temporal lobe,"Fukutake, T.",2003,,,0,
4286,A case of progressive multifocal leukoencephalopathy with Takayasu arteritis and indolent adult T-cell lymphoma/leukemia,"A 65-year-old man with Takayasu arteritis in a stable condition was admitted to our hospital because of rapid progressive dementia. Brain FLAIR/T2-weighted magnetic resonance images revealed high signal intensity in the diffuse subcortical white matter. John Cunningham virus (JCV) genome in cerebrospinal fluid was detected by polymerase chain reaction. Finally, progressive multifocal leukoencephalopathy was diagnosed definitely by brain biopsy. In addition, the patient was found to be complicated by chronic/smoldering adult T-cell leukemia/lymphoma. The administration of mefloquine with mirtazapine was early started within two months after the onset. However, the combination treatment led to no improvement in symptoms and lesion size. The patient died six months after the onset. Therefore, this case suggested that both of HTLV-I infection and B cell abnormalities due to Takasasu arteritis impaired the therapeutic effect.",,"Fukumoto, S.;Shiraishi, H.;Nakamichi, K.;Nakajima, H.;Saijyo, M.;Tsujino, A.",2016,Mar 8,10.5692/clinicalneurol.cn-000776,0,
4287,Different clinical effect of four antidementia drugs for Alzheimer's disease patients depending on white matter severity,"AIM: To examine the clinical effect of four antidementia drugs (donepezil, galantamine, rivastigmine and memantine) in Alzheimer's disease patients who were divided into subgroups based on their periventricular hyperintensity (PVH) severity. METHODS: A total of 551 Alzheimer's disease patients (201 men and 350 women) were divided into four subgroups based on their PVH severity (0-III). They received monotherapy for 12 months. We compared the clinical effects at the baseline, and at 3, 6 and 12 months after initiation. RESULTS: The baseline age became higher with PVH grades, and the Mini-Mental State Examination and Hasegawa Dementia Scale-Revised showed a decrease that was dependent on white matter severity. Although the PVH 0 subgroup showed stable cognitive, affective and ADL functions until 12 months in all four drug groups, the PVH I subgroup showed an improved Apathy Scale from the baseline in response to memantine at 3 and 9 months (P < 0.05), and galantamine at 9 months (P < 0.01). In the PVH II subgroup, the Mini-Mental State Examination showed a significant improvement from the baseline in response to galantamine (P < 0.05) at 9 months and Hasegawa Dementia Scale-Revised (P < 0.05) at 3 months. In the PVH III subgroup, cognitive and affective functions were preserved in all four drug groups until 12 months, but activities of daily living deteriorated in the riverstigmine group at 6 and 12 months (P < 0.05). CONCLUSIONS: The present study shows that these four drugs showed sensitivity dependent on white matter severity that clinically affected cognitive, affective and activities of daily living functions. Geriatr Gerontol Int 2017; 17: 1991-1999.",Alzheimer's disease;antidementia drug;magnetic resonance imaging;periventricular hyperintensity;white matter lesions,"Fukui, Y.;Hishikawa, N.;Ichinose, J.;Sato, K.;Nakano, Y.;Morihara, R.;Ohta, Y.;Yamashita, T.;Abe, K.",2017,Nov,,0,
4288,Different clinical effect of four antidementia drugs for Alzheimer's disease patients depending on white matter severity,"AIM: To examine the clinical effect of four antidementia drugs (donepezil, galantamine, rivastigmine and memantine) in Alzheimer's disease patients who were divided into subgroups based on their periventricular hyperintensity (PVH) severity. METHODS: A total of 551 Alzheimer's disease patients (201 men and 350 women) were divided into four subgroups based on their PVH severity (0-III). They received monotherapy for 12 months. We compared the clinical effects at the baseline, and at 3, 6 and 12 months after initiation. RESULTS: The baseline age became higher with PVH grades, and the Mini-Mental State Examination and Hasegawa Dementia Scale-Revised showed a decrease that was dependent on white matter severity. Although the PVH 0 subgroup showed stable cognitive, affective and ADL functions until 12 months in all four drug groups, the PVH I subgroup showed an improved Apathy Scale from the baseline in response to memantine at 3 and 9 months (P < 0.05), and galantamine at 9 months (P < 0.01). In the PVH II subgroup, the Mini-Mental State Examination showed a significant improvement from the baseline in response to galantamine (P < 0.05) at 9 months and Hasegawa Dementia Scale-Revised (P < 0.05) at 3 months. In the PVH III subgroup, cognitive and affective functions were preserved in all four drug groups until 12 months, but activities of daily living deteriorated in the riverstigmine group at 6 and 12 months (P < 0.05). CONCLUSIONS: The present study shows that these four drugs showed sensitivity dependent on white matter severity that clinically affected cognitive, affective and activities of daily living functions. Geriatr Gerontol Int 2017; **: **-**.",Alzheimer's disease;antidementia drug;magnetic resonance imaging;periventricular hyperintensity;white matter lesions,"Fukui, Y.;Hishikawa, N.;Ichinose, J.;Sato, K.;Nakano, Y.;Morihara, R.;Ohta, Y.;Yamashita, T.;Abe, K.",2017,Mar 09,,0,4287
4289,Prevalence and clinical implication of microbleeds in dementia with lewy bodies in comparison with microbleeds in Alzheimer's disease,"BACKGROUND: Cerebral microbleeds (MBs) have been well investigated in Alzheimer's disease (AD), but not very extensively in non-AD dementias or in dementia with Lewy bodies (DLB). AIMS: To elucidate the clinical significance of MBs in DLB. METHODS: We compared the prevalence, locations and risk factors for MBs in 59 DLB and 81 AD patients. We visually counted MBs in each of the cortical and subjacent areas (frontal, temporal, parietal and occipital), the basal ganglia and the thalamus, and the brainstem and the cerebellar hemispheres on 1.5-tesla T2*-weighted gradient-recalled-echo MRI images. White matter lesions were semiquantified in fluid-attenuated inversion recovery images according to the Fazekas rating scale. RESULTS: While the prevalence of MBs was comparable, MBs tended to be more abundant in DLB than in AD in all brain areas with the exception of the occipital lobes. The number of MBs was positively associated with the severity of white matter lesions but not with other vascular risk factors in either AD or DLB. The presence of MBs could be associated with cognitive impairment at onset. MB-positive DLB patients showed less impairment on (123)I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy) images, supporting the notion of an inverse relationship between vascular lesions and Lewy body pathology. CONCLUSION: It was suggested that an intricate association between Lewy body pathology, AD-type pathologies and vascular lesions seems to be related to the initial symptoms and results of MIBG scintigraphy in DLB.",,"Fukui, T.;Oowan, Y.;Yamazaki, T.;Kinno, R.",2013,Jan,10.1159/000351423,0,
4290,Do lesions involving the cortical cholinergic pathways help or hinder efficacy of donepezil in patients with Alzheimer's disease?,"AIMS: To investigate the influences of vascular lesions detected by MRI, lesions involving the cortical cholinergic pathways and hippocampal thickness on therapeutic responsiveness to donepezil in patients with Alzheimer's disease (AD). METHODS: The study cohort contained 67 patients with probable AD. We used the revised Hasegawa Dementia Rating (HDS-R) and the Clock Drawing Test (CDT) to evaluate drug efficacy for 24 months. The Cholinergic Pathways Hyperintensities Scale (CHIPS), a newly developed visual scale, was used to semiquantify lesions on the cholinergic pathways. RESULTS: Over the 24-month period, the results of the CDT showed more apparent and constant association with white matter hyperintensities (WMH) and lesions on the cholinergic pathways than the HDS-R. WMH may enhance, while lesions on the cholinergic pathways may attenuate sensitivity to donepezil treatment when judged by the CDT. No apparent association between the thicknesses of hippocampi with baseline cognition or therapeutic responsiveness to donepezil was found. CONCLUSION: Donepezil may be more efficacious when further executive dysfunction caused by WMH is added to AD dementia and less so when cholinergic reserves are further impinged upon by lesions involving the cortical cholinergic pathways.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*drug therapy/*pathology;Cerebral Cortex/*drug effects/*pathology;Cholinergic Fibers/*drug effects/*pathology;Cholinesterase Inhibitors/*pharmacology/*therapeutic use;Cohort Studies;Female;Hippocampus/drug effects/pathology;Humans;Indans/*therapeutic use;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/*drug effects/*pathology;Neuropsychological Tests;Piperidines/*therapeutic use;Treatment Outcome","Fukui, T.;Hieda, S.;Bocti, C.",2006,,10.1159/000095801,0,
4291,"Brain MRI of reversible, recurrent white matter lesions in a patient with a 35-year history of neuro-Behçet disease","Neuro-Behçet disease (NBD) can be categorized clinically as the acute type - characterized by meningoencephalitis - and the chronic progressive type - characterized by slowly progressive dementia, ataxia, and dysarthria. We describe a 35-year clinical course of NBD that was characterized by slowly progressive ataxia and dysarthria despite continued corticosteroid treatment. Because of difficulties in swallowing, which interrupted oral corticosteroid therapy, this case was characterized by recurrent manifestations of neurological symptoms and abnormal MRI findings. Resumption of corticosteroid therapy was effective. The patient was a 77-year-old woman who had presented with oral ulceration and dysarthria at the age of 42. She suffered from Entero-Behçet disease at the age of 52 and was treated with corticosteroids for 7 years. Oral corticosteroid therapy was resumed at the age of 64, but her neurological deficit slowly progressed and she developed paraplegia with dysphagia and dysarthria. Corticosteroids treatment was interrupted when she was 76; one year later, she was hospitalized in a state of somnolence. Brain MRI scans revealed new lesions with gadolinium enhancement. We diagnosed acute exacerbation of NBD attacks on the basis of positive findings for HLA-B51, protein elevation, and IL-6 in the cerebrospinal fluid. Corticosteroid treatment was effective. She became alert, and her MRI findings were no longer abnormal. Corticosteroids administration was continued via percutaneous endoscopic gastrostomy. Our case suggested that even if neurological exacerbation is not obvious during the clinical course, immunosuppressive therapies should be continued for patients with chronic NBD to prevent acute aggravation.",betamethasone;gadolinium;HLA B51 antigen;interleukin 6;prednisolone;aged;antigen detection;article;ataxia;case report;cerebrospinal fluid analysis;clinical feature;contrast enhancement;corticosteroid therapy;course evaluation;disease exacerbation;drug withdrawal;dysarthria;dysphagia;female;hospitalization;human;image analysis;meningoencephalitis;mouth ulcer;neuro Behcet disease;neurologic disease;nuclear magnetic resonance imaging;paraplegia;percutaneous endoscopic gastrostomy;protein content;somnolence;treatment response;white matter,"Fukuda, K.;Ishida, S.;Sakane, S.;Furukawa, K.;Sugino, M.",2009,,,0,
4292,"[Brain MRI of reversible, recurrent white matter lesions in a patient with a 35-year history of neuro-Behcet disease]","Neuro-Behcet disease (NBD) can be categorized clinically as the acute type--characterized by meningoencephalitis--and the chronic progressive type- characterized by slowly progressive dementia, ataxia, and dysarthria. We describe a 35-year clinical course of NBD that was characterized by slowly progressive ataxia and dysarthria despite continued corticosteroid treatment. Because of difficulties in swallowing, which interrupted oral corticosteroid therapy, this case was characterized by recurrent manifestations of neurological symptoms and abnormal MRI findings. Resumption of corticosteroid therapy was effective. The patient was a 77-year-old woman who had presented with oral ulceration and dysarthria at the age of 42. She suffered from Entero-Behcet disease at the age of 52 and was treated with corticosteroids for 7 years. Oral corticosteroid therapy was resumed at the age of 64, but her neurological deficit slowly progressed and she developed paraplegia with dysphagia and dysarthria. Corticosteroids treatment was interrupted when she was 76; one year later, she was hospitalized in a state of somnolence. Brain MRI scans revealed new lesions with gadolinium enhancement. We diagnosed acute exacerbation of NBD attacks on the basis of positive findings for HLA-B51, protein elevation, and IL-6 in the cerebrospinal fluid. Corticosteroid treatment was effective. She became alert, and her MRI findings were no longer abnormal. Corticosteroids administration was continued via percutaneous endoscopic gastrostomy. Our case suggested that even if neurological exacertion is not obvious during the clinical course, immunosuppressive therapies should be continued for patients with chronic NBD to prevent acute aggravation.",Aged;Behcet Syndrome/complications/*diagnosis/drug therapy/pathology;Brain/*pathology;Cognition Disorders/etiology;Disease Progression;Female;Glucocorticoids/administration & dosage;Humans;*Magnetic Resonance Imaging;Prednisolone/administration & dosage;Recurrence;Time Factors,"Fukuda, K.;Ishida, S.;Sakane, S.;Furukawa, K.;Sugino, M.",2009,Jun,,0,
4293,Frontal white matter lesions and dementia in lacunar infarction,"We studied the associations of mental deterioration and blood pressure with severity and location of lesions in the cerebral white matter of 35 patients (27 men and eight women) aged 52-84 (mean 70.9) years with multiple lacunar infarcts; 21 had no dementia and 14 were demented. Using magnetic resonance imaging to evaluate lesion severity, we determined that demented patients had more severe lesions than nondemented patients; this difference was especially prominent for lesions in the frontal lobe (p less than 0.001). Score on the dementia rating scale of Hasegawa et al was negatively correlated with severity of the lesions in the frontal lobe. Blood pressure was positively correlated with the severity of white matter lesions. We show that severity of lesions in the white matter, especially in the frontal lobe, is correlated with mental deterioration of patients with multiple lacunar infarcts. Because uncontrolled hypertension is related to the severity of such lesions, careful selection of antihypertensive treatment is important in preventing both the cerebral lesions and the associated mental deterioration.","Aged;Aged, 80 and over;Brain/ pathology;Cerebral Infarction/complications/ diagnosis;Dementia/diagnosis/ etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales;Retrospective Studies","Fukuda, H.;Kobayashi, S.;Okada, K.;Tsunematsu, T.",1990,Aug,,0,
4294,Comparison of iodine-123-iomazenil SPECT and technetium-99m-HMPAO-SPECT in Alzheimer's disease,"This study was designed to elucidate a central type of benzodiazepine (Bz) receptor distribution in patients with Alzheimer's disease using SPECT with [123I]iomazenil (IMZ). METHODS: Eight patients with probable Alzheimer's disease were studied. Benzodiazepine receptor imaging was performed 15 min (early) and 180 min (delayed) after intravenous administration of 167 MBq IMZ, sequentially, using hexamethylpropylene amine oxime (HMPAO) SPECT to evaluate regional cerebral perfusion. RESULTS: Early IMZ-SPECT depicted areas of reduced uptake in sites of decreased cerebral blood flow (CBF), but each area of decreased uptake was extended wider than the area of hypoperfusion. Delayed IMZ-SPECT images demonstrated a similar pattern of decreased area of CBF; the affected region in Bz receptor bindings, however, was clearer and broader compared with that in either HMPAO-SPECT or early IMZ-SPECT. In comparison with the uptakes for the normal cerebral hemisphere (ratio to the contralateral cerebellum) in patients with unilateral cerebral infarction as a control group (n = 4), the patients with Alzheimer's disease showed distinctive bilateral frontal or parietal defects (p < 0.05). CONCLUSION: Brain SPECT using IMZ may be more sensitive than CBF images in patients with Alzheimer's disease.","Alzheimer Disease/ radionuclide imaging;Brain/metabolism;Female;Flumazenil/ analogs & derivatives/pharmacokinetics;Humans;Image Processing, Computer-Assisted;Iodine Radioisotopes/pharmacokinetics;Male;Middle Aged;Organotechnetium Compounds/pharmacokinetics;Oximes/pharmacokinetics;Technetium Tc 99m Exametazime;Tissue Distribution;Tomography, Emission-Computed, Single-Photon","Fukuchi, K.;Hashikawa, K.;Seike, Y.;Moriwaki, H.;Oku, N.;Ishida, M.;Fujita, M.;Uehara, T.;Tanabe, H.;Kusuoka, H.;Nishimura, T.",1997,Mar,,0,
4295,Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: A new entity?,"We studied a dominant hereditary disorder showing progressive spastic paraparesis. The symptoms began in early childhood, with cerebellar deficits and mild mental deterioration, and the subsequent appearance of limb spasticity resulted in severe disability in the 3rd-4th decades of life. None of the patients were associated with any somatic abnormalities. Brain MRI showed diffuse white-matter involevement in all affected patients, but not in unaffected siblings. Although dominant, recessive, or X-linked leukodpstrophies cause similar clinical features, our family did not show any known biochemical or gene deficits characteristic of these disorders. The clinical, radiological, and biochemical findings of this family are reported and suggest a possible novel genetic disorder.",adolescent;adult;article;biochemistry;cerebellum disease;clinical article;clinical feature;disability;dominant inheritance;female;human;leukodystrophy;mental deterioration;nuclear magnetic resonance imaging;onset age;priority journal;radiology;school child;spastic paraplegia;symptom;white matter,"Fukazawa, T.;Sasaki, H.;Kikuchi, S.;Hamada, K.;Hamada, T.;Tashiro, K.",1997,,,0,
4296,Simultaneous impairment of intracranial and peripheral artery vasoreactivity in CADASIL patients,"BACKGROUND: Reduced cerebrovascular reactivity (CVR) is an important step in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The present study utilized quantitative single photon emission computed tomography (SPECT) with the autoradiographic (ARG) method and reactive hyperemia peripheral arterial tonometry (RH-PAT) to assess vasoreactivity in intracranial arteries and in peripheral arteries in patients with CADASIL. METHODS: Quantitative SPECT studies were conducted in eight patients with CADASIL, while RH-PAT analysis was conducted in eight CADASIL patients and in eight age-matched normal subjects. Quantitative SPECT studies with the ARG method were performed at baseline and after administration of acetazolamide. Regional cerebral blood flow (rCBF) values were measured using stereotactic extraction estimation (SEE) methods. The rCBF of CADASIL patients was averaged in the bilateral frontal, temporal, parietal, and occipital lobes as well as in the limbic system, cerebellar hemisphere, whole cerebral cortex and basal ganglia. The CVR index from acetazolamide stress of intracranial arteries was calculated in each area. Vasoreactivity of peripheral arteries was estimated by the reactive hyperemia index (RHI) measured with a PAT device before and after interruption of arterial flow. RESULTS: Average RHI after post-deflation was lower in CADASIL patients than in normal subjects. RHI correlated significantly with CVR in all brain areas in CADASIL patients. CONCLUSIONS: Vasoreactivity is reduced in peripheral arteries and in intracranial arteries in patients with CADASIL.","Acetazolamide;Adult;Aged;Amphetamines;Analysis of Variance;Autoradiography;CADASIL/*physiopathology/radionuclide imaging;Case-Control Studies;Cerebral Arteries/*physiopathology;*Cerebrovascular Circulation;Female;Fingers/*blood supply;Humans;Hyperemia/physiopathology;Japan;Magnetic Resonance Imaging;Male;Manometry;Middle Aged;Predictive Value of Tests;Radiopharmaceuticals;Regional Blood Flow;Tomography, Emission-Computed, Single-Photon","Fujiwara, Y.;Mizuno, T.;Okuyama, C.;Nagakane, Y.;Watanabe-Hosomi, A.;Kondo, M.;Kuriyama, N.;Tokuda, T.;Matsushima, S.;Nishimura, T.;Nakagawa, M.",2012,,10.1159/000334185,0,
4297,Early protective effect of bone marrow mononuclear cells against ischemic white matter damage through augmentation of cerebral blood flow,"BACKGROUND AND PURPOSE: To investigate the efficacy of bone marrow mononuclear cell (BMMNC) treatment against ischemic white matter (WM) damage in a hypoperfused brain. METHODS: Mice were administered intravenous treatment of vehicle, spleen-derived marrow mononuclear cells (MNCs), or BMMNCs (5 x 10(6) cells) obtained from enhanced green fluorescent protein transgenic mice 24 hours after bilateral common carotid artery stenosis (BCAS), and then euthanized at either 1 day or 30 days after treatment. RESULTS: Laser speckle perfusion imaging analyses revealed marked recovery of cerebral blood flow (CBF) in the early phase after BMMNC treatment (6 hours after administration), before histological evidence of angiogenesis was assessed by fluorescein-isothiocyanate-dextran perfusion assay. BMMNC treatment induced an increase in vascular endothelial growth factor and Ser1177 phosphorylated endothelial nitric oxide synthase levels in the BCAS-induced mouse brains at 1 day after the treatment. BCAS-induced ischemic WM lesions were significantly improved 30 days after BMMNC treatment despite any evidence of direct structural incorporation of donor BMMNCs into endothelial cells and oligodendrocytes. Instead, enhanced green fluorescent protein-positive donor cells with morphological features of pericytes were observed in the vessel walls. Post-BMMNC administration of an NOS inhibitor abolished early CBF recovery and produced protective effects against ischemic WM damage. CONCLUSIONS: BMMNC treatment provides marked protection against ischemic WM damage, enhancing CBF in the early phase and in subsequent angiogenesis, both of which involve nitric oxide synthase activation. These findings suggest promise for the application of BMMNCs for subcortical ischemic vascular dementia.","Animals;Blotting, Western;Bone Marrow Transplantation;Brain/ pathology;Brain Chemistry/physiology;Brain Ischemia/pathology/ therapy;Capillaries/pathology;Carotid Stenosis/pathology/therapy;Cell Differentiation/physiology;Cerebrovascular Circulation/ physiology;Enzyme-Linked Immunosorbent Assay;Flow Cytometry;Fluorescent Antibody Technique;Green Fluorescent Proteins;Male;Mice;Mice, Inbred C57BL;Mice, Transgenic;Neovascularization, Physiologic/physiology;Nitric Oxide Synthase Type III/biosynthesis;Phosphorylation;Vascular Endothelial Growth Factor A/metabolism","Fujita, Y.;Ihara, M.;Ushiki, T.;Hirai, H.;Kizaka-Kondoh, S.;Hiraoka, M.;Ito, H.;Takahashi, R.",2010,Dec,10.1161/strokeaha.110.596379,0,
4298,Progress of leukoaraiosis is inhibited by correction of platelet hyper-aggregability,"BACKGROUND: Platelet hyper-aggregability is an important risk factor for leukoaraiosis. In this study we investigated whether aggravation of leukoaraiosis can be controlled by means of long-term correction of platelet hyper-aggregability. METHODS: Twenty-one patients with leukoaraiosis and uncorrected platelet hyper-aggregability were compared with 21 controls matched for age, grade of leukoaraiosis and observation period whose platelet hyper-aggregability was corrected. Platelet aggregability was estimated by an optical analytical method with a nine-stage display using two different concentrations each of adenosine diphosphate (ADP) and collagen (the double ADP method). RESULTS: The mean observation period between two magnetic resonance imaging (MRI) scans for both groups was 4.1 years. In the non-corrected group, moderate to severe aggravation of leukoaraiosis was observed in a large number of patients. In the corrected group, only a small number of patients showed generally mild aggravation of leukoaraiosis. The number of patients showing aggravation of periventricular hyperintensity (PVH) was 7 in 21 in the non-corrected group versus 1 in 21 (p = 0.022) in the corrected group, and for aggravation of deep white-matter hyperintensity, these values were 9 in 21 versus 4 in 21, respectively. Thus, the difference was more significant if the degree of aggravation was taken into account. CONCLUSION: The progress of leukoaraiosis is greatly inhibited by long-term correction of platelet hyper-aggregability.","Aged;Anti-Inflammatory Agents, Non-Steroidal/ therapeutic use;Antihypertensive Agents/therapeutic use;Aspirin/ therapeutic use;Brain/pathology/physiopathology;Dementia, Vascular/epidemiology/prevention & control;Diabetes Mellitus/epidemiology;Female;Humans;Hypercholesterolemia/epidemiology;Hypertension/complications/drug therapy;Leukoaraiosis/ drug therapy/epidemiology/ physiopathology;Magnetic Resonance Imaging;Male;Obesity/epidemiology;Platelet Aggregation Inhibitors/ therapeutic use;Risk Factors;Tobacco Use Disorder/epidemiology","Fujita, S.;Kawaguchi, T.;Uehara, T.;Fukushima, K.",2005,Dec,10.1017/s104161020500164x,0,
4299,A case of late adult-onset dentatorubral-pallidoluysian atrophy (DRPLA) successfully treated with V-P shunt operation,"A 44-year-old Japanese man was diagnosed as having late adult-onset dentatorubral-pallidoluysian atrophy (DRPLA), whose CAG repeats in the DRPLA gene were 60 and 15. He developed gait disturbance, limb ataxia, pyramidal tract signs, dementia, and psychiatric symptoms including character changes within a few years of the above diagnosis. His T 2-weighted brain MRI showed symmetric high-signal lesions in the cerebral white matter and brain stem, in addition to cerebellar, brain stem, and cerebral cortical atrophy. Since the result of RI cisternography indicated that he manifested the clinical features of normal pressure hydrocephalus (NPH), V-P shunt operation was done. In a week after the operation, his gait disturbance, pyramidal tract signs, dementia and psychiatric symptoms were remarkably improved. White matter lesions have been thought to be concomitant with late adult-onset DRPLA patients, but some of these patients may have characteristics of NPH pathophysiology.",adult;article;ataxia;brain ventricle peritoneum shunt;case report;cisternography;dementia;dentatorubropallidoluysian atrophy;gait disorder;human;image analysis;male;normotensive hydrocephalus;nuclear magnetic resonance imaging;onset age;pathophysiology;personality disorder;pyramidal tract;trinucleotide repeat,"Fujita, N.;Tabe, H.;Shimohata, T.;Makino, K.;Nagai, H.",1998,,,0,
4300,Neuroimaging in the differential diagnosis of prion disease,"MRI including diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) is useful for the diagnosis of prion disease, particularly Creutzfeldt-Jakob disease (CJD). Hyperintensity lesions are predominant on DWI, and are often seen in the cerebral cortex (""cortical ribboning"") or both in the cerebral cortex and striatum (anterior dominant). However, clinical and MRI findings of CJD can be mimicked by those of many other dementing conditions, including autoimmune encephalitis. Non-prion diagnosis should be considered when hyperintensity is predominant on FLAIR, apparent diffusion coefficient (ADC) is increased early, the lesion is symmetric, the limbic region is most affected, or ADC is decreased in the white matter.",Creutzfeldt Jakob disease;differential diagnosis;human;neuroimaging;nuclear magnetic resonance imaging;prion disease,"Fujita, K.",2013,,,0,4301
4301,Neuroimaging in the differential diagnosis of prion disease,"MRI including diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) is useful for the diagnosis of prion disease, particularly Creutzfeldt-Jakob disease (CJD). Hyperintensity lesions are predominant on DWI, and are often seen in the cerebral cortex (""cortical ribboning"") or both in the cerebral cortex and striatum (anterior dominant). However, clinical and MRI findings of CJD can be mimicked by those of many other dementing conditions, including autoimmune encephalitis. Non-prion diagnosis should be considered when hyperintensity is predominant on FLAIR, apparent diffusion coefficient (ADC) is increased early, the lesion is symmetric, the limbic region is most affected, or ADC is decreased in the white matter.",,"Fujita, K.",2013,2013,,0,
4302,"Deep white matter lesions on MRI, and not silent brain infarcts are related to headache and dizziness of non-specific cause in non-stroke Japanese subjects","OBJECTIVE: Silent or asymptomatic cerebrovascular disease is believed to be an important risk factor for symptomatic stroke and vascular dementia. Although non-specific complaints such as mild to moderate headache and/or dizziness may also be caused by silent stroke, which remains a topic of controversy. METHODS: To investigate the relationship between silent brain infarcts and non-specific complaints, we assessed findings on magnetic resonance images using a common protocol in the following three groups of subjects; Group 1:78 subjects with non-specific complaints, Group 2:47 subjects with vascular risk factors, and Group 3:75 normal subjects without any subjective complaints or vascular risk factors. In addition to silent stroke, deep white matter lesions on MRI were also evaluated. All subjects were recruited from 12 institutes of the study group located at various parts of Japan. RESULTS: Silent brain infarcts were demonstrated in 44%, 43%, and 20% of subjects in Groups 1, 2, and 3, respectively. In Group 1, the average number of infarcts per individual who had silent brain infarction was 1.8, which was significantly fewer than 3.8 in Group 2 or 3.5 in Group 3 (p<0.0167). White matter lesions were found in 68%, 49%, and 11% in Groups 1, 2, and 3, respectively, indicating that non-specific complaints are more closely related to deep white matter lesions than to silent infarct lesions. Such white matter lesions were found more frequently in subjects with depressive state than in non-depressed subjects (67% vs. 39%, p=0.0155). CONCLUSION: The present results suggest that deep white matter lesions, rather than silent brain infarcts, appear to be important in producing headache and/or dizziness of non-specific cause and also to be related to the depressive state.",Aged;Brain/pathology;Brain Infarction/diagnosis;Cerebrovascular Disorders/ complications/diagnosis;Depressive Disorder/complications/diagnosis;Dizziness/ etiology;Female;Headache/ etiology;Humans;Japan;Magnetic Resonance Imaging;Male;Middle Aged,"Fujishima, M.;Yao, H.;Terashi, A.;Tagawa, K.;Matsumoto, M.;Hara, H.;Akiguchi, I.;Suzuki, K.;Nishimaru, K.;Udaka, F.;Gyoten, T.;Takeuchi, J.;Hamada, R.;Yoshida, Y.;Ibayashi, S.",2000,Sep,,0,
4303,"Mild cognitive impairment, poor episodic memory, and late-life depression are associated with cerebral cortical thinning and increased white matter hyperintensities","In various independent studies to date, cerebral cortical thickness and white matter hyperintensity (WMH) volume have been associated with episodic memory, depression, and mild cognitive impairment (MCI). The aim of this study was to uncover variations in cortical thickness and WMH volume in association with episodic memory, depressive state, and the presence of MCI simultaneously in a single study population. The participants were 186 individuals with MCI (clinical dementia rating [CDR] of 0.5) and 136 healthy elderly controls (HCs; CDR of 0) drawn from two community-based cohort studies in northern Japan. We computed cerebral cortical thickness and WMH volume by using MR scans and statistically analyzed differences in these indices between HCs and MCI participants. We also assessed the associations of these indices with memory performance and depressive state in participants with MCI. Compared with HCs, MCI participants exhibited thinner cortices in the temporal and inferior parietal lobes and greater WMH volumes in the corona radiata and semioval center. In MCI participants, poor episodic memory was associated with thinner cortices in the left entorhinal region and increased WMH volume in the posterior periventricular regions. Compared with non-depressed MCI participants, depressed MCI participants showed reduced cortical thickness in the anterior medial temporal lobe and gyrus adjacent to the amygdala bilaterally, as well as greater WMH volume as a percentage of the total intracranial volume (WMHr). A higher WMHr was associated with cortical thinning in the frontal, temporal, and parietal regions in MCI participants. These results demonstrate that episodic memory and depression are associated with both cortical thickness and WMH volume in MCI participants. Additional longitudinal studies are needed to clarify the dynamic associations and interactions among these indices.",aged;amygdaloid nucleus;article;brain cortex;brain region;cohort analysis;controlled study;corona radiata (brain);corpus callosum;cortical thickness (brain);demography;entorhinal cortex;episodic memory;female;fusiform gyrus;human;inferior temporal gyrus;Japan;late life depression;lateral brain ventricle;left hemisphere;major clinical study;male;memory disorder;mild cognitive impairment;Mini Mental State Examination;nervous system parameters;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;parahippocampal gyrus;parietal gyrus;parietal lobe;poor episodic memory;semioval center;spinal cord ventral horn;supramarginal gyrus;temporal lobe;uncus;very elderly;Wechsler memory scale;white matter;white matter hyperintensity;Achieva 1.5T MRI scanners,"Fujishima, M.;Maikusa, N.;Nakamura, K.;Nakatsuka, M.;Matsuda, H.;Meguro, K.",2014,,,0,
4304,Alzheimer's disease or Alzheimer's syndrome?: a longitudinal computed tomography neuroradiological follow-up study of 56 cases diagnosed clinically as Alzheimer's disease,"BACKGROUND: Some 200 patients, including those with Alzheimer's disease and other types of dementia, stay year-round in Yokohama - Houyuu Hospital. They undergo computed tomography (CT) neuroradiological examination at least once or twice a year. For this study, the accumulative data, including clinical and neuroradiological, were analyzed. METHODS: Differential diagnoses of Alzheimer's disease were performed in accordance with the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. The 56 patients (15 men, 41 women) included in this study underwent in-hospital observation on average for 4.4 years (range: 1-10 years). The patients were classified into four groups according to the age of disease onset. The CT findings were summarized for each group and then compared among the groups to determine if there were any differences related to age of onset and, if so, to identify and analyze them. RESULTS: (1) The duration of deceased cases' total clinical course (in years) compared among the four groups. In general, the degree of dementia was more severe among those with earlier disease onset. (2) In cases admitted within 2 years from onset (n =14), the suspected initiating focus of cortical atrophy occurred in the frontal lobe (n = 6), the temporal lobe (n = 6), or the fronto-temporal lobes (n = 2). (3) Although CT findings generally showed that the more severe cases had earlier onset, serial CT examinations in each case showed widely different pathologies in degree, nature and manner of progression, regardless of group classification. (4) The earliest sites of brain atrophy, sites of its severest involvement within the brain, and neuroradiological development of the cerebral cortex pathology in combination with hemispheric white matter, lateral ventricles, and third ventricles varied among the four groups and between case within each group. Alzheimer's disease could not be subclassified simply by the age of clinical onset. CONCLUSION: Cases of so-called Alzheimer's disease, as observed through continued clinical follow-up and serial CT examinations, appear so diverse in symptomatology and radiological pathomorphology that it is difficult to consider them a single nosological entity. The pathology of Alzheimer's disease has to be reconsidered in accordance with the variety observed in the sequential development of neuroradiological findings. The pathology must be reconstructed in terms of topographical dimensions and chronological developments. The diagnosis of Alzheimer's disease appears to be not so simple based on any conventional diagnostic operational standards.",Alzheimer's disease;CT longitudinal follow-up;nosological heterogeneity,"Fujisawa, K.;Tsunoda, S.;Hino, H.;Shibuya, K.;Takeda, A.;Aoki, N.",2015,Dec,10.1111/psyg.12162,0,
4305,Binswanger's disease: Clinical and computed tomography neuroradiological study of seven cases,"Background: Binswanger's disease is a special type of vascular dementia, which requires further reappraisal and redefinition. In a geriatric psychiatry hospital (with 207 beds), we treated several patients who probably had this disease, and tried to establish a basis for making a clinical diagnosis. Methods: From 2001 to 2005, we treated seven inpatients with noteworthy symptoms, who had been under observation in hospital wards for between 4 and 19 months. Here, for these patients, we examine the history of the illness, the condition of the patients at admission, the clinical course, and serial computed tomography (CT) findings. Results: Characteristic features of the clinical courses and symptoms of these patients were: (i) onset occurred late in life (patients were aged in their 70s and 80s); (ii) vascular events were atypical and transient, leaving few permanent neurological sequelae; (iii) progression of dementia and other somatic or neurologic symptoms was continuous and fast in four patients, and rather gradual in three patients; (iv) there was an alternating or changing pattern in all patients' state of consciousness, mood, behavior, or manner of respiration; symptoms such as mutism, lack of facial expression, and apparent indifference were counterbalanced with such behaviors as occasional unexpected smiles, pertinent verbal responses, and sincere gazes; (v) significant negative symptoms were a lack of dysarthria, lack of dysphagia, lack of involuntary movement, and occasional lack of muscle rigidity. The primary CT findings were: (i) moderate to severe generalized (involving whole of centrum semiovale), diffuse and homogeneous (except one patient) leukoaraiosis of the hemispheric white matter, including the temporal lobe (except one patient), all (except one patient) frontal and parietal dominant, with the corpus callosum involved in one case; (ii) diffuse and generalized atrophy of the pallium, most marked in the frontal and parietal lobes, restricted to the frontal and parietal lobes in three patients, and to the frontal, parietal and temporal lobes in four patients; (iii) atrophy of the medial temporal lobe was inconstant and, when present, ambiguous in degree; (iv) slight to moderate enlargement of the bilateral lateral and third ventricles; (v) a few small lacunae in the basal ganglia and thalamus in one patient, inhomogeneous macular changes of density in the basal ganglia and thalamus in two patients, and no such findings in the remaining four patients. Conclusion: We have described a group of patients with dementia characterized by a clinical course with episodes of rather transient vascular intervention, psychopathology characteristic of organic dementia, fluctuating psychotic symptoms in combination, and intensive extensive homogeneous leukoaraiosis of the hemispheric white matter on CT. These clinical and CT neuroradiological findings seem to warrant the clinical diagnosis of Binswanger's disease, which should be reconfirmed at autopsy. Early research on this disease by Binswanger, Alzheimer, Nissl and others is reviewed. Some points of differential diagnosis in serial neuroradiology are discussed in relation to multilacunar dementia.",aged;anamnesis;article;behavior change;Binswanger encephalopathy;brain atrophy;breathing pattern;clinical article;clinical feature;computer assisted tomography;consciousness;dementia;disease course;female;gerontopsychiatry;hospital admission;human;hypertension;leukoaraiosis;male;mood change;neuroradiology;priority journal;temporal lobe,"Fujisawa, K.;Tsunoda, S.;Hino, H.;Segawa, M.",2005,,,0,
4306,Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury,"Case report: A 6-year-old boy was admitted to our hospital 20 min after receiving a direct impact to his head in an automobile accident. He was semi-comatose on admission and computed tomography showed acute epidural hematoma in the right supratentorial region. Three hours later, his consciousness deteriorated due to the enlargement of the hematoma. Surgical removal of hematoma relieved his consciousness disturbance. Post-operative magnetic resonance imaging revealed spotty high-intensity lesions in the corpus callosum on T2-weighted images, and a solitary high-intensity lesion in the left caudate nucleus extending to the medial globus pallidum on T2-weighted and diffusion-weighted images. Magnetic resonance angiography showed no abnormality in the main arteries. These results suggested cerebral infarction in the vascular territory supplied by the recurrent artery of Heubner in association with diffuse brain injury. Post-operative course was uneventful and he was discharged without neurological deficit. Conclusions: Post-traumatic cerebral infarction in the caudate nucleus is extremely rare, and its association with diffuse brain injury and epidural hematoma is apparently unique. © Springer-Verlag 2004.",,"Fujimura, M.;Kameyama, M.;Motohashi, O.;Kon, H.;Ishii, K.;Onuma, T.",2004,June,,0,
4307,Incidence of silent cerebral infarction in patients with major depression,"Background and Purpose: There have been few studies of the incidence of silent cerebral infarction detected by magnetic resonance imaging in patients with presenile or senile major depression. Methods: We examined silent cerebral infarction in patients with presenile and senile major depression who were diagnosed at Hiroshima Prefectural Hospital. The diagnostic criteria of the American Psychiatric Association (DSM-III-R) were used. Patients with stroke or focal neurological symptoms were excluded. Results: Silent cerebral infarction was observed in 51.4% of the patients with presenile-onset presenile depression, and the incidence was significantly higher than in patients with juvenile-onset presenile depression (P<.01). Among the patients with senile major depression, silent cerebral infarction was observed in 65.9% of those with presenile-onset depression and in 93.7% of those with senile-onset depression. Conclusions: Our findings suggest that half of presenile-onset major depression and the majority of senile-onset major depression might be organic depression related to silent cerebral infarction. Because major depression occurring for the first time during or after the presenile period may be related to silent cerebral infarction, it is important to keep this possibility in mind when treating such patients.",,"Fujikawa, T.;Yamawaki, S.;Touhouda, Y.",1993,1993,,0,
4308,A case of panencephalopathic type of Creutzfeldt-Jakob disease,"We serially examined a 76-year-old woman with panencephalopathic type of Creutzfeldt-Jakob disease (CJD) using MR imaging. Serial T2-weighted MR images clearly showed that localized hyperintense areas in the periventricular regions observed in the early stage of CJD, progressively extended to the subcortical white matter. In the neuropathological specimens, marked spongiform changes and gemistocytic astrocytosis were found in the cerebral white matter. These MR imaging and neuropathologic findings support that diffuse white matter degeneration is primary damage caused by CJD.",,"Fujii, S.;Matsusue, E.;Ogawa, T.;Kinoshita, T.;Sugihara, S.;Tanaka, H.;Saito, J.;Ohama, E.",2004,2004,,0,
4309,[Neuropsychological evaluation and MRI in Alzheimer's disease and multi-infarct dementia],,"Aged;Alzheimer Disease/*diagnosis/psychology;Brain/pathology/radionuclide imaging;Dementia/*diagnosis/psychology;Diagnosis, Differential;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged","Fujii, M.;Fukatsu, M.;Takahata, N.;Takahashi, T.;Morita, K.",1987,,,0,
4310,A case of hypoglycemia caused by the accidental ingestion of glimepiride in an elderly dementia patient diagnosed based on the serum glimepiride concentration,"A 77-year-old man being treated for Alzheimer-type dementia and an old cerebral infarction was admitted to our hospital due to disturbance of consciousness. The patient's Mini-mental State Examination and Hasegawa Dementia Scale scores were 23 and 17 points, respectively. His blood glucose level was low (18 mg/dl), with a relatively high insulin level (15.2 μU/ml). Computed tomography and an 18-hour fasting test showed no signs of insulinoma. Since his wife had been taking medications for dementia and diabetes, including Glimepiride, we considered the possibility that he may have taken glimepiride by mistake. Five months later, he was admitted again due to severe hypoglycemia with a relatively high insulin level (23.4 μU/ml). More than 660 g of glucose and 100 mg of hydrocortisone were administered, and the hypoglycemia resolved approximately 24 hours after admission. Again, there were no signs of insulinoma. We asked Sanofi-Aventis to measure the level of glimepiride in a blood sample obtained six hours after admission. Glimepiride was detected at a concentration of 24.48 ng/ml, which roughly corresponded to the accidental ingestion of 6 mg of the drug. We were later informed by the patient's home doctor that he had visited the emergency department of another prefecture hospital with the same symptoms. Thereafter, the couple received counseling by their home doctor, and the hypoglycemia has not recurred since. Given the increase in the number of elderly households, an increase in the number of episodes of accidental ingestion of medicine is expected. Clinicians should be aware of the potential for accidental exposure to drugs prescribed to other family members especially, in elderly patients. © 2013 The Japan Geriatrics Society.",antidiabetic agent;glimepiride;sulfonylurea derivative;aged;article;blood;case report;chemically induced disorder;dementia;human;hypoglycemia;male;medication error,"Fujieda, N.;Hazekawa, I.;Araki, E.",2013,,,0,
4311,Vascular change and opposing effects of the angiotensin type 2 receptor in a mouse model of vascular cognitive impairment,"Our aims were to assess the spatiotemporal development of brain pathology in a mouse model of chronic hypoperfusion using magnetic resonance imaging (MRI), and to test whether the renin-angiotensin system (RAS) can offer therapeutic benefit. For the first time, different patterns of cerebral blood flow alterations were observed in hypoperfused mice that ranged from an immediate and dramatic to a delayed decrease in cerebral perfusion. Diffusion tensor imaging revealed increases in several quantitative parameters in different brain regions that are indicative of white-matter degeneration; this began around 3 weeks after induction of hypoperfusion. While this model may be more variable than previously reported, neuroimaging tools represent a promising way to identify surrogate markers of pathology. Vascular remodelling was observed in hypoperfused mice, particularly in the anterior part of the Circle of Willis. While the angiotensin II receptor type 2 agonist, Compound 21 (C21), did not influence this response, it did promote expansion of the basilar artery in microcoil animals. Furthermore, C21-treated animals exhibited increased brain lymphocyte infiltration, and importantly, C21 had opposing effects on spatial reference memory in hypoperfused and sham mice. These results suggest that the RAS may have a role in vascular cognitive impairment.","Angiotensin II Type 2 Receptor Blockers/pharmacology;Animals;Brain/drug effects/metabolism/ pathology;Cerebrovascular Circulation/drug effects/ physiology;Dementia, Vascular/metabolism/ pathology;Disease Models, Animal;Flow Cytometry;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mice;Mice, Inbred C57BL;Receptor, Angiotensin, Type 2/ metabolism","Fuchtemeier, M.;Brinckmann, M. P.;Foddis, M.;Kunz, A.;Po, C.;Curato, C.;Dirnagl, U.;Farr, T. D.",2015,Mar,10.1038/jcbfm.2014.221,0,
4312,The value of diffusion tensor imaging in the differential diagnosis of subcortical ischemic vascular dementia and Alzheimer's disease in patients with only mild white matter alterations on T2-weighted images,"BACKGROUND: Diffusion tensor imaging (DTI) is a form of functional magnetic resonance imaging (MRI) that allows examination of the microstructural integrity of white matter in the brain. Dementia is a neurodegenerative disease, and DTI can provide indirect insights of the microstructural characteristics of brains in individuals with different forms of dementia. PURPOSE: To evaluate the value of DTI in the diagnosis and differential diagnosis of patients with subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD). MATERIAL AND METHODS: The study included 40 patients (20 AD patients and 20 SIVD patients) and 20 normal controls (NC). After routine MRI and DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured and compared in regions of interest (ROI). RESULTS: Compared to NC and AD patients, SIVD patients had lower FA values and higher ADC values in the inferior-fronto-occipital fascicles (IFOF), genu of the corpus callosum (GCC), splenium of the corpus callosum (SCC), and superior longitudinal fasciculus (SLF). Compared to controls and SIVD patients, AD patients had lower FA values in the anterior frontal lobe, temporal lobe, hippocampus, IFOF, GCC, and CF; and higher ADC values in the temporal lobe and hippocampus. CONCLUSION: DTI can be used to estimate the white matter impairment in dementia patients. There were significant regional reductions of FA values and heightened ADC values in multiple regions in SIVD patients compared to AD patients. When compared with conventional MRI, DTI may provide a more objective method for the differential diagnosis of SIVD and AD disease patients who have only mild white matter alterations on T2-weighted imaging.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/pathology;Brain Mapping/methods;Dementia, Vascular/ pathology;Diagnosis, Differential;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/ pathology;Severity of Illness Index","Fu, J. L.;Zhang, T.;Chang, C.;Zhang, Y. Z.;Li, W. B.",2012,Apr 1,,0,
4313,The value of diffusion tensor imaging in the differential diagnosis of subcortical ischemic vascular dementia and Alzheimer's disease in patients with only mild white matter alterations on T2-weighted images,"Diffusion tensor imaging (DTI) is a form of functional magnetic resonance imaging (MRI) that allows examination of the microstructural integrity of white matter in the brain. Dementia is a neurodegenerative disease, and DTI can provide indirect insights of the microstructural characteristics of brains in individuals with different forms of dementia. To evaluate the value of DTI in the diagnosis and differential diagnosis of patients with subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD). The study included 40 patients (20 AD patients and 20 SIVD patients) and 20 normal controls (NC). After routine MRI and DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured and compared in regions of interest (ROI). Compared to NC and AD patients, SIVD patients had lower FA values and higher ADC values in the inferior-fronto-occipital fascicles (IFOF), genu of the corpus callosum (GCC), splenium of the corpus callosum (SCC), and superior longitudinal fasciculus (SLF). Compared to controls and SIVD patients, AD patients had lower FA values in the anterior frontal lobe, temporal lobe, hippocampus, IFOF, GCC, and CF; and higher ADC values in the temporal lobe and hippocampus. DTI can be used to estimate the white matter impairment in dementia patients. There were significant regional reductions of FA values and heightened ADC values in multiple regions in SIVD patients compared to AD patients. When compared with conventional MRI, DTI may provide a more objective method for the differential diagnosis of SIVD and AD disease patients who have only mild white matter alterations on T2-weighted imaging.",,"Fu, J. L.;Zhang, T.;Chang, C.;Zhang, Y. Z.;Li, W. B.",1987,1,,0,4312
4314,Use of Diffusion tensor imaging for evaluating changes in the microstructural integrity of white matter over 3 years in patients with amnesic-type mild cognitive impairment converting to Alzheimer's disease,"BACKGROUND AND PURPOSE: Patients with amnestic mild cognitive impairment (aMCI) are at risk of developing Alzheimer's disease (AD). It is therefore important to identify biomarkers of conversion to AD. This study examined whether the integrity of white matter can predict this conversion. METHODS: Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological features of aMCI subjects (n = 41) were compared with normal controls (n = 20) for 12-36 months. RESULTS: Compared to controls, 22 aMCI subjects had lower fractional anisotropy (FA) values in the cingulate fasciculus (CF) at baseline, and 19 of those converted to AD during follow-up. Only two of the other 19 aMCI patients converted to AD. Compared to baseline, AD converters showed lower FA values in the anterior frontal lobe, temporal lobe, hippocampus, inferior fronto-occipital fascicles, corpus callosum genu and CF, and higher apparent diffusion coefficient values in the temporal lobe and hippocampus. CONCLUSIONS: Those aMCI subjects with lower than normal FA values in the CF were more likely to convert to AD. The connectivity of the hippocampus and cingulate bundles may be affected in the early stage of AD. Impairment of white matter and fiber bundles was more severe at the AD stage than the aMCI stage. © 2013 by the American Society of Neuroimaging.",,"Fu, J. L.;Liu, Y.;Li, Y. M.;Chang, C.;Li, W. B.",2014,July/August,,0,
4315,A vascular approach to mild amnestic cognitive impairment: A pilot study,"Objective: Mild cognitive impairment (MCI) is a subtle memory disorder not matching criteria for dementia. There is evidence for vascular comorbidity in several types of dementia. We hypothesized that neurovascular workup would detect a high degree of vascular disease in patients with MCI. Materials and methods: In cooperation with our memory clinic, patients with amnestic MCI were referred to our department for neurovascular investigation. The workup encompassed ultrasound examination with carotid duplex including Intima-Media-Thickness (IMT) measurement, and transcranial Doppler (TCD) including one-hour microemboli monitoring, cerebrovascular reactivity measurement and Bubble test. Cerebral MRI for the evaluation of vascular and white-matter lesions, brain atrophy, hippocampal volumes, and amyloid angiopathy was performed. Results: Ten patients were included. Vascular risk factors were present in six patients. Four patients had atherosclerotic lesions, three classified as mild, and one as moderate carotid stenosis. IMT > 1 mm was found in two patients, with a maximum IMT of 1.11 mm. None of the patients with acceptable bone window had intracranial stenosis in TCD. Vasoreactivity was pathologically low in one patient. Permanent right-left shunt was found in three patients, of which one showed spontaneous cerebral microembolism. Hippocampal volume reduction and cortical atrophy were found in four patients. Chronic ischemic changes in MRI were present in one patient, and three patients had subcortical infarctions. Cortical infarctions, microbleeds, or amyloid angiopathy were not found. Conclusions: Pure amnestic MCI is probably less associated with cerebrovascular disease and may be more consistent with evolving Alzheimer's disease. However, vascular risk factors are common in these patients. © 2012 John Wiley & Sons A/S.",adult;aged;arterial wall thickness;article;brain atrophy;brain damage;brain size;carotid artery;carotid artery obstruction;cerebrovascular disease;clinical article;hippocampus;human;microembolism;mild cognitive impairment;nuclear magnetic resonance imaging;risk factor;transcranial doppler;vascular amyloidosis;white matter,"Fromm, A.;Lundervold, A. J.;Moen, G.;Skulstad, S.;Thomassen, L.",2013,,10.1111/ane.12054,0,4316
4316,A vascular approach to mild amnestic cognitive impairment: a pilot study,"OBJECTIVE: Mild cognitive impairment (MCI) is a subtle memory disorder not matching criteria for dementia. There is evidence for vascular comorbidity in several types of dementia. We hypothesized that neurovascular workup would detect a high degree of vascular disease in patients with MCI. MATERIALS AND METHODS: In cooperation with our memory clinic, patients with amnestic MCI were referred to our department for neurovascular investigation. The workup encompassed ultrasound examination with carotid duplex including Intima-Media-Thickness (IMT) measurement, and transcranial Doppler (TCD) including one-hour microemboli monitoring, cerebrovascular reactivity measurement and Bubble test. Cerebral MRI for the evaluation of vascular and white-matter lesions, brain atrophy, hippocampal volumes, and amyloid angiopathy was performed. RESULTS: Ten patients were included. Vascular risk factors were present in six patients. Four patients had atherosclerotic lesions, three classified as mild, and one as moderate carotid stenosis. IMT > 1 mm was found in two patients, with a maximum IMT of 1.11 mm. None of the patients with acceptable bone window had intracranial stenosis in TCD. Vasoreactivity was pathologically low in one patient. Permanent right-left shunt was found in three patients, of which one showed spontaneous cerebral microembolism. Hippocampal volume reduction and cortical atrophy were found in four patients. Chronic ischemic changes in MRI were present in one patient, and three patients had subcortical infarctions. Cortical infarctions, microbleeds, or amyloid angiopathy were not found. CONCLUSIONS: Pure amnestic MCI is probably less associated with cerebrovascular disease and may be more consistent with evolving Alzheimer's disease. However, vascular risk factors are common in these patients.","Aged;Body Mass Index;Brain;Cerebrovascular Disorders/*epidemiology;Comorbidity;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/*diagnosis/epidemiology;Neuropsychological Tests;Pilot Projects;Risk Factors;Severity of Illness Index;Ultrasonography, Doppler","Fromm, A.;Lundervold, A. J.;Moen, G.;Skulstad, S.;Thomassen, L.",2013,,10.1111/ane.12054,0,
4317,Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma: A prospective longitudinal study,"Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests. © 2013 Springer Science+Business Media New York.",dexamethasone;temozolomide;adult;aged;article;brain atrophy;cancer patient;clinical article;cognitive defect;controlled study;disease association;female;follow up;functional disease;glioma;human;human tissue;longitudinal study;male;mental deterioration;multiple cycle treatment;neuropsychological test;neurotoxicity;nuclear magnetic resonance imaging;prospective study;scoring system;standardization;tumor growth;white matter lesion,"Froklage, F. E.;Oosterbaan, L. J.;Sizoo, E. M.;De Groot, M.;Bosma, I.;Sanchez, E.;Douw, L.;Heimans, J. J.;Reijneveld, J. C.;Lagerwaard, F. J.;Buter, J.;Uitdehaag, B. M. J.;Klein, M.;Postma, T. J.",2014,,,0,
4318,Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry,"OBJECTIVES: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction-a proxy of atrophy-in Alzheimer's disease. METHODS: Twenty nine probable Alzheimer's patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimer's patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimer's patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimer's group (p<0.0001 uncorrected). RESULTS: When all Alzheimer's patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimer's patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right. CONCLUSIONS: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimer's disease.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Atrophy;Brain/ pathology;Brain Mapping/methods;Dominance, Cerebral/physiology;Female;Humans;Image Processing, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Linear Models;Magnetic Resonance Imaging/ methods;Male;Mental Status Schedule;Middle Aged;Reference Values","Frisoni, G. B.;Testa, C.;Zorzan, A.;Sabattoli, F.;Beltramello, A.;Soininen, H.;Laakso, M. P.",2002,Dec,,0,
4319,The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium,"BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Seven academic sites of the European Alzheimer's Disease Consortium (EADC) enrolled 19 patients with mild cognitive impairment (MCI), 22 with AD, and 18 older healthy persons by using the ADNI clinical and neuropsychological battery. ADNI compliant magnetic resonance imaging (MRI) scans, cerebrospinal fluid, and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater by using visual rating scales. RESULTS: Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioral, and neuropsychological features of the European subjects were very similar to their U.S. counterparts. Three-dimensional T1-weighted MRI sequences were successfully performed on all subjects, and cerebrospinal fluid samples were obtained from 77%, 68%, and 83% of AD patients, MCI patients, and controls, respectively. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI patients (0.9, 0.8) to AD patients (2.3, 2.0), whereas mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US-ADNI subjects. CONCLUSIONS: Academic EADC centers can adopt the ADNI platform to enroll MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US-ADNI.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/ pathology/ physiopathology;Brain/ pathology/ physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Pilot Projects","Frisoni, G. B.;Henneman, W. J.;Weiner, M. W.;Scheltens, P.;Vellas, B.;Reynish, E.;Hudecova, J.;Hampel, H.;Burger, K.;Blennow, K.;Waldemar, G.;Johannsen, P.;Wahlund, L. O.;Zito, G.;Rossini, P. M.;Winblad, B.;Barkhof, F.",2008,Jul,10.1016/j.jalz.2008.04.009,0,
4320,Computed tomography in the detection of the vascular component in dementia,"We evaluated the presence and type of vascular lesions with computerized tomography (CT) in 94 cognitively impaired elderly patients who had been defined as degenerative (Alzheimer's disease, AD) or vascular (multi-infarct dementia, MID) dementia patients on the basis of clinical data. Twenty-six percent of the 77 AD, but only 59% of the 17 MID patients had vascular lesions. The most represented vascular lesions were leukoaraiosis in AD and hemispherical cortical lesions in MID patients. Age, signs indicative of, and risk factors for vascular disease were associated with vascular lesions on CT. We conclude that CT scan is a necessary complement to historical and clinical data in the detection of vascularity in demented patients.","Aged;Aged, 80 and over;Alzheimer Disease/complications/*radiography;Brain/radiography;Cerebrovascular Disorders/complications/radiography;Dementia, Multi-Infarct/radiography;Dementia, Vascular/*radiography;Female;Humans;Male;*Tomography, X-Ray Computed","Frisoni, G. B.;Beltramello, A.;Binetti, G.;Bianchetti, A.;Weiss, C.;Scuratti, A.;Trabucchi, M.",1995,,,0,
4321,Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease,"Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD.","Alzheimer Disease/*diagnosis/*pathology;Analysis of Variance;Australia;Brain/*pathology;Diagnosis, Differential;Frontotemporal Dementia/*diagnosis/*pathology;Germany;Humans;Magnetic Resonance Imaging/methods;Organ Size/physiology","Frings, L.;Yew, B.;Flanagan, E.;Lam, B. Y.;Hull, M.;Huppertz, H. J.;Hodges, J. R.;Hornberger, M.",2014,,10.1371/journal.pone.0090814,0,
4322,Longitudinal cerebral diffusion changes reflect progressive decline of language and cognition,"Language deficits are regularly found in cortical neurodegenerative diseases. The progression of language deficits shows a considerable inter-individual variability even within one diagnostic group. We aimed at detecting patterns of altered diffusion as well as atrophy of cerebral gray and white matter which underlie ongoing language-related deterioration in patients with cortical neurodegenerative diseases. Diffusion tensor imaging and T1-weighted MRI data of 26 patients with clinically diagnosed neurodegenerative disorders were acquired at baseline and 14 months later in this prospective study. Language functions were assessed with a confrontation naming test and the Token Test. Diffusion and voxel-based morphometric measures were calculated and correlates of language performance were evaluated. Across all patients, the naming impairment was related to diffusion (false discovery rate-corrected P<0.05 at baseline) and atrophy abnormalities (family-wise error (FWE)-corrected P<0.05 at follow-up) primarily in the left temporal lobe. Deficits in the Token Test were correlated with predominantly left frontal MRI abnormalities (FWE-corrected P<0.05). The Token Test performance decline over 14 months was accompanied by further increasing abnormalities in the frontal cortex, left caudate, parietal cortex (all FWE-corrected P<0.05), and posterior callosal body (FWE-corrected P=0.055). Both diffusion and structural MRI were apt to elucidate the underpinnings of inter-individual differences in language-related deficits and to detect longitudinal changes that accompanied ongoing cognition and language decline, with mean diffusivity appearing most sensitive. This might indicate the usefulness of diffusion measures as markers for successful intervention in therapy studies.",Aged;Atrophy;Cerebral Cortex/ pathology/ physiopathology;Cognition;Cognition Disorders/complications/ pathology/ physiopathology/psychology;Dementia/complications/ pathology/ physiopathology/psychology;Diffusion Tensor Imaging;Female;Humans;Language;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged,"Frings, L.;Dressel, K.;Abel, S.;Mader, I.;Glauche, V.;Weiller, C.;Hull, M.",2013,Dec 30,10.1016/j.pscychresns.2013.08.003,0,
4323,Diagnostic utility of novel mri-Based biomarkers for alzheimer's disease: Diffusion tensor imaging and deformation-based morphometry,"We report evidence that multivariate analyses of deformation-based morphometry and diffusion tensor imaging (DTI) data can be used to discriminate between healthy participants and patients with Alzheimer's disease (AD) with comparable diagnostic accuracy. In contrast to other studies on MRI-based biomarkers which usually only focus on a single modality, we derived deformation maps from high-dimensional normalization of T1-weighted images, as well as mean diffusivity maps and fractional anisotropy maps from DTI of the same group of 21 patients with AD and 20 healthy controls. Using an automated multivariate analysis of the entire brain volume, widespread decreased white matter integrity and atrophy effects were found in cortical and subcortical regions of AD patients. Mean diffusivity maps and deformation maps were equally effective in discriminating between AD patients and controls (AUC =0.88 vs. AUC=0.85) while fractional anisotropy maps performed slightly inferior. Combining the maps from different modalities in a logistic regression model resulted in a classification accuracy of AUC=0.86 after leave-one-out cross-validation. It remains to be shown if this automated multivariate analysis of DTI-measures can improve early diagnosis of AD in predementia stages. © 2010 - IOS Press and the authors. All rights reserved.",,"Friese, U.;Meindl, T.;Herpertz, S. C.;Reiser, M. F.;Hampel, H. G.;Teipel, S. J.",2010,2010,,0,
4324,Detection of Alzheimer's disease with diffusion tensor imaging and deformation-based morphometry,"Novel MRI based acquisition and analysis techniques are increasingly used as biomarkers to discriminate between Alzheimer's disease and normal aging. Evaluating the diagnostic utility of the various approaches in use is difficult though because of significant methodological differences between studies. In this research we directly compare the diagnostic utility of deformation-based morphometry (DBM) and diffusion tensor imaging (DTI) with data derived from the same group of patients with probable AD and healthy control participants. DBM was used to assess regional relative volume reductions in patients compared to controls. Distributed cortical atrophy effects were found in frontal, parietal, and temporal regions. As DTI measures, mean diffusivity and fractional anisotropy were employed to index white matter integrity. The results also point to widespread decline of white matter integrity in frontal, parieto-occipital, and temporal regions in AD. Concerning diagnostic utility, we found that the discrimination performance was best for maps of mean diffusivity and DBM. In a logistic regression model a combination of modalities reached a classification accuracy of AUC = 0.86 after leave-one-out cross-validation. We discuss the results with regard to the feasibility of current MRI based biomarkers for future applications in clinical research settings. © 2011 The authors and IOS Press. All rights reserved.",,"Friese, U.;Meindl, T.;Herpertz, S. C.;Reiser, M. F.;Hampel, H.;Teipel, S. J.",2011,2011,,0,
4325,Early changes of brain connectivity in primary open angle glaucoma,"Our aim was to assess in primary open angle glaucoma (POAG), a major cause of irreversible blindness worldwide, whether diffuse brain changes recently shown in advanced stage can be detected since the early stage. We used multimodal magnetic resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing. Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group along the visual pathway and in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed decreased functional connectivity (FC) in the visual (P = 0.004) and working memory (P < 0.001) networks whereas an increase occurred in the default mode (P = 0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already present in early POAG (n = 14) in both visual and nonvisual systems (P </= 0.01). Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was associated with worsening AC in both visual and nonvisual pathway (P < 0.001), progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of the structural and functional alterations within and outside the visual system showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG includes widespread damage of AC and altered FC within and beyond the visual system since the early disease stage. The association of brain MRI changes with measures of visual severity emphasizes the clinical relevance of our findings. Hum Brain Mapp 37:4581-4596, 2016. (c) 2016 Wiley Periodicals, Inc.","Atrophy;Brain/ diagnostic imaging/ physiopathology;Brain Mapping;Diffusion Tensor Imaging;Disease Progression;Female;Glaucoma, Open-Angle/ diagnostic imaging/ physiopathology;Gray Matter/diagnostic imaging/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multimodal Imaging;Neural Pathways/diagnostic imaging/physiopathology;Rest;Tomography, Optical Coherence;Visual Field Tests;Alzheimer disease;Dti;connectivity;functional magnetic resonance imaging;glaucoma;neurodegeneration","Frezzotti, P.;Giorgio, A.;Toto, F.;De Leucio, A.;De Stefano, N.",2016,Dec,,0,4326
4326,Early changes of brain connectivity in primary open angle glaucoma,"Our aim was to assess in primary open angle glaucoma (POAG), a major cause of irreversible blindness worldwide, whether diffuse brain changes recently shown in advanced stage can be detected since the early stage. We used multimodal magnetic resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing. Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group along the visual pathway and in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed decreased functional connectivity (FC) in the visual (P = 0.004) and working memory (P < 0.001) networks whereas an increase occurred in the default mode (P = 0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already present in early POAG (n = 14) in both visual and nonvisual systems (P </= 0.01). Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was associated with worsening AC in both visual and nonvisual pathway (P < 0.001), progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of the structural and functional alterations within and outside the visual system showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG includes widespread damage of AC and altered FC within and beyond the visual system since the early disease stage. The association of brain MRI changes with measures of visual severity emphasizes the clinical relevance of our findings. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.",Alzheimer disease;Dti;atrophy;connectivity;functional magnetic resonance imaging;glaucoma;magnetic resonance imaging;neurodegeneration,"Frezzotti, P.;Giorgio, A.;Toto, F.;De Leucio, A.;De Stefano, N.",2016,Aug 9,10.1002/hbm.23330,0,
4327,White matter hyperintensities potentiate hippocampal volume reduction in non-demented older individuals with abnormal amyloid-β,"Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n=24), mild cognitive impairment (MCI) (n=26), and subjective cognitive complaints (SCC) (n=37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n=87) and in the non-demented group (including SCC and MCI individuals only, n=63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.",amyloid beta protein[1-42];adult;aged;Alzheimer disease;article;brain size;cerebrovascular disease;cognitive defect;female;hippocampus;human;lacunar stroke;major clinical study;male;mild cognitive impairment;nuclear magnetic resonance imaging;priority journal;radiological parameters;subjective cognitive complaint;white matter hyperintensity,"Freeze, W. M.;Jacobs, H. I. L.;Gronenschild, E. H.;Jansen, J. F. A.;Burgmans, S.;Aalten, P.;Clerx, L.;Vos, S. J.;Van Buchem, M. A.;Barkhof, F.;Van Der Flier, W. M.;Verbeek, M. M.;Rikkert, M. O.;Backes, W. H.;Verhey, F. R.",2016,,10.3233/jad-160474,0,
4328,White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-beta,"Cerebral small vessel disease (cSVD) and amyloid-beta (Abeta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Abeta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Abeta pathology was assessed as cerebrospinal fluid-derived Abeta1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Abeta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Abeta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Abeta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Abeta42 levels, but not in individuals with normal CSF Abeta42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Abeta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.",0 (Amyloid beta-Peptides);0 (Biomarkers);Aged;Alzheimer Disease/cerebrospinal fluid/diagnostic imaging;Amyloid beta-Peptides/ cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Cerebral Hemorrhage/diagnostic imaging;Cerebral Small Vessel Diseases/cerebrospinal fluid/ diagnostic imaging;Cognition;Cognitive Dysfunction/cerebrospinal fluid/diagnostic imaging;Cross-Sectional Studies;Female;Hippocampus/ diagnostic imaging;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Organ Size;Perception;White Matter/ diagnostic imaging;Amyloid-beta;cerebral small vessel disease;dementia;neurodegeneration,"Freeze, W. M.;Jacobs, H. I.;Gronenschild, E. H.;Jansen, J. F.;Burgmans, S.;Aalten, P.;Clerx, L.;Vos, S. J.;van Buchem, M. A.;Barkhof, F.;van der Flier, W. M.;Verbeek, M. M.;Rikkert, M. O.;Backes, W. H.;Verhey, F. R.;Le, A. R. N. project",2017,,,0,
4329,White Matter Hyperintensities Potentiate Hippocampal Volume Reduction in Non-Demented Older Individuals with Abnormal Amyloid-beta,"Cerebral small vessel disease (cSVD) and amyloid-beta (Abeta) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Abeta have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Abeta pathology was assessed as cerebrospinal fluid-derived Abeta1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Abeta on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Abeta and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Abeta and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Abeta42 levels, but not in individuals with normal CSF Abeta42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Abeta levels are at an increased risk of accelerated disease progression when concomitant cSVD is present.",Amyloid-beta;cerebral small vessel disease;dementia;neurodegeneration,"Freeze, W. M.;Jacobs, H. I.;Gronenschild, E. H.;Jansen, J. F.;Burgmans, S.;Aalten, P.;Clerx, L.;Vos, S. J.;van Buchem, M. A.;Barkhof, F.;van der Flier, W. M.;Verbeek, M. M.;Rikkert, M. O.;Backes, W. H.;Verhey, F. R.",2016,Sep 20,10.3233/jad-160474,0,
4330,"Adult onset leukodystrophy with neuroaxonal spheroids: Clinical, neuroimaging and neuropathologic observations","Pigmented orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids are two adult onset leukodystrophies with neuroaxonal spheroids presenting with prominent neurobehavioral, cognitive and motor symptoms. These are familial or sporadic disorders characterized by cerebral white matter degeneration including myelin and axonal loss, gliosis, macrophages and axonal spheroids. We report clinical, neuroimaging and pathological correlations of four women ages 34-50 years with adult onset leukodystrophy. Their disease course ranged from 1.5-8 years. Three patients had progressive cognitive and behavioral changes; however, one had acute onset. Neuroimaging revealed white matter abnormalities characterized by symmetric, bilateral, T2 hyperintense and T1 hypointense Magnetic Resonance Imaging signal involving frontal lobe white matter in all patients. Extensive laboratory investigations were negative apart from abnormalities in some mitochondrial enzymes and immunologic parameters. Autopsies demonstrated severe leukodystrophy with myelin and axonal loss, axonal spheroids and macrophages with early and severe frontal white matter involvement. The extent and degree of changes outside the frontal lobe appeared to correlate with disease duration. The prominent neurobehavioral deficits and frontal white matter disease provide clinical-pathologic support for association pathways linking distributed neural circuits sub-serving cognition. These observations lend further support to the notion that white matter disease alone can account for dementia. © 2008 The Authors.",,"Freeman, S. H.;Hyman, B. T.;Sims, K. B.;Hedley-Whyte, E. T.;Vossough, A.;Frosch, M. P.;Schmahmann, J. D.",2009,January,,0,
4331,Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study,"OBJECTIVES: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC). METHODS: Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. RESULTS: Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (+/- 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (+/- 1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: beta: 0.39, 95% CI: 0.13-0.90, p = 0.008; follow-up: beta: 0.24, 95% CI: 0.10-0.38, p = 0.001) and processing speed (baseline: beta: 0.48, 95% CI: 0.14-0.89, p = 0.005; follow-up: beta: 0.15, 95% CI: 0.02-0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (beta: 0.11, 95% CI: 0-0.22, p = 0.04). CONCLUSION: Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC.","Activities of Daily Living;Aged;Aged, 80 and over;Brain/physiopathology;Cognition/physiology;Dementia/physiopathology;Executive Function/*physiology;Female;Humans;Magnetic Resonance Imaging;Male;Memory, Short-Term/*physiology;Middle Aged;Mild Cognitive Impairment/physiopathology;Motor Activity/*physiology;Neuropsychological Tests;Prospective Studies;Regression Analysis;White Matter/pathology;age-related white matter changes;cognitive;executive function;memory;physical activity;processing speed","Frederiksen, K. S.;Verdelho, A.;Madureira, S.;Bazner, H.;O'Brien, J. T.;Fazekas, F.;Scheltens, P.;Schmidt, R.;Wallin, A.;Wahlund, L. O.;Erkinjunttii, T.;Poggesi, A.;Pantoni, L.;Inzitari, D.;Waldemar, G.",2015,Jul,10.1002/gps.4220,0,
4332,Effect of moderate-to-high intensity aerobic exercise on hippocampus and cortical regions in patients with mild Alzheimer's disease,"Background and aims: Alzheimer's disease (AD) is characterised by specific pathological changes including atrophy of cortical areas and the hippocampus. In this study, we assessed the effects of an aerobic exercise program on brain structure measured by MRI in patients with AD. Methods: The ADEX study is a multi-centre RCT, which investigated the effect of a supervised aerobic program on symptoms and biomarkers of AD. 200 patients with mild AD were randomised to either exercise (60-minute exercise sessions three times a week for 16 weeks) or to usual care. A subgroup of 42 patients (control group: n=20; exercise group: n=22; table 1) underwent 3T MRI at baseline and follow-up to assess cortical volume and thickness. For total exercise load, attendance and intensity were monitored. Changes in regional brain volumes (hippocampal subfields, parahippocampus, caudate and putamen) and cortical thickness (temporal, cingulate, precuneus; parietal, temporal-occipital, fusiform, parahippocampus, frontal cortex; pre- and post-central cortex) were quantified using Freesurfer, with cortical regions defined according to the Destrieux atlas. White matter hyperintensities (WMH) were quantified using Jim image analysis package. Results: There was no significant effect of the intervention on cortical thickness or volume. Exercise load showed a positive correlation with change in volume in hippocampal subfields, as well as frontal cortical thickness in the exercise group. Conclusion: In this relatively small sample, exercise does not seem to affect cortical volume or thickness in patients with AD. (Table Presented).",hippocampus;patient;aerobic exercise;human;European;neurology;Alzheimer disease;exercise;cortical thickness (brain);thickness;follow up;imaging software;white matter;image analysis;precuneus;control group;putamen;frontal cortex;nuclear magnetic resonance imaging;brain size;brain;atrophy;biological marker,"Frederiksen, K. S.;Larsen, C. T.;Christensen, A. N.;Hasselbalch, S.;Hogh, P.;Wermuth, L.;Lolk, A.;Andersen, B. B.;Siebner, H. R.;Waldemar, G.;Garde, E.",2017,,,0,
4333,Corpus Callosum Atrophy in Patients with Mild Alzheimer's Disease,"Background/Objectives: Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain, such as age-related white matter changes (ARWMC) and progression of the disease. Meth ods: Twenty-eight patients in the early stages of AD and 50 non-demented elderly subjects with varying degrees of ARWMC were investigated using MRI. The CC was assessed semi-automatically, and ARWMC were rated according to the Fazekas scale. Results: A significant difference in posterior CC size could be detected between non-demented elderly subjects and early stage AD patients. The sizes of the total CC, rostral body and splenium at baseline were correlated with change from baseline MMSE score after a 1-year follow-up in AD patients. There was no association between CC size and ARWMC. Conclusions: The present findings indicate that posterior CC atrophy is present in mild AD independently of ARWMC. Furthermore, CC atrophy may be associated with cognitive deterioration. Copyright © 2011 S. Karger AG, Basel.",patient;atrophy;Alzheimer disease;corpus callosum;aged;mental deterioration;brain;white matter;nuclear magnetic resonance imaging;Mini Mental State Examination;follow up,"Frederiksen, K. S.;Garde, E.;Skimminge, A.;Ryberg, C.;Rostrup, E.;Baaré, W. F. C.;Siebner, H. R.;Hejl, A. M.;Leffers, A. M.;Waldemar, G.",2011,,,0,
4334,The role of carotid intima-media thickness in predicting longitudinal cognitive function in an older adult cohort,"BACKGROUND AND PURPOSE: Carotid atherosclerosis is a risk factor for cerebrovascular disease in older adults. Although age-related cognitive decline has been associated with cerebrovascular disease, not much is known about the consequences of carotid atherosclerosis on longitudinal cognitive function. This study examines the longitudinal relationship between atherosclerosis and cognition in a sample of non-demented older subjects using baseline measurements of carotid intima media thickness (CIMT) and annual cognitive measures of executive function (EXEC) and verbal memory (MEM). METHODS: Baseline measurements included CIMT derived from B-mode carotid artery ultrasound, structural T1-weighted images of white matter hypointensities (WMH), white matter lesions (WML), and cerebral infarct. Hypertension, low-density lipoprotein (LDL), diabetes, and waist to hip ratios (WHR) were included as covariates in our models to control for cerebrovascular risks and central adiposity. Annual composite scores of EXEC and MEM functions were derived from item response theory. Linear mixed models were used to model longitudinal cognitive change. RESULTS: A significant inverse relationship was found between baseline CIMT and annual EXEC score, but not annual MEM score. Subjects included in the highest 4th quartile of CIMT showed a rate of annual decline in EXEC score that was significant relative to subjects in lower quartile groups (p<0.01). The relationship between the 4th quartile of CIMT and annual EXEC score remained significant after independently adjusting for imaging measures of white matter injury and cerebral infarct. CONCLUSIONS: Older adult subjects with the highest index of CIMT showed an annual decline in EXEC scores that was significant relative to subjects with lower quartile measurements of CIMT, independent of our measures of white matter injury and cerebral infarct. Our findings suggest that elevated measures of CIMT may mark an atherosclerotic state, resulting in a decline in executive function and not memory in non-demented older adults.","Aged;Aged, 80 and over;Brain/pathology;Carotid Artery Diseases/ epidemiology/ultrasonography;Carotid Intima-Media Thickness;Cognition;Cognition Disorders/ epidemiology/pathology;Executive Function;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory;Middle Aged;Neuropsychological Tests;Prospective Studies;White Matter/ pathology","Frazier, D. T.;Seider, T.;Bettcher, B. M.;Mack, W. J.;Jastrzab, L.;Chao, L.;Weiner, M. W.;DeCarli, C.;Reed, B. R.;Mungas, D.;Chui, H. C.;Kramer, J. H.",2014,,10.1159/000366469,0,
4335,Resting-state global functional connectivity as a biomarker of cognitive reserve in mild cognitive impairment,"Cognitive reserve (CR) shows protective effects in Alzheimer’s disease (AD) and reduces the risk of dementia. Despite the clinical significance of CR, a clinically useful diagnostic biomarker of brain changes underlying CR in AD is not available yet. Our aim was to develop a fully-automated approach applied to fMRI to produce a biomarker associated with CR in subjects at increased risk of AD. We computed resting-state global functional connectivity (GFC), i.e. the average connectivity strength, for each voxel within the cognitive control network, which may sustain CR due to its central role in higher cognitive function. In a training sample including 43 mild cognitive impairment (MCI) subjects and 24 healthy controls (HC), we found that MCI subjects with high CR (> median of years of education, CR+) showed increased frequency of high GFC values compared to MCI-CR- and HC. A summary index capturing such a surplus frequency of high GFC was computed (called GFC reserve (GFC-R) index). GFC-R discriminated MCI-CR+ vs. MCI-CR-, with the area under the ROC = 0.84. Cross-validation in an independently recruited test sample of 23 MCI subjects showed that higher levels of the GFC-R index predicted higher years of education and an alternative questionnaire-based proxy of CR, controlled for memory performance, gray matter of the cognitive control network, white matter hyperintensities, age, and gender. In conclusion, the GFC-R index that captures GFC changes within the cognitive control network provides a biomarker candidate of functional brain changes of CR in patients at increased risk of AD.",clinical article;cognitive reserve;controlled study;education;executive function;female;functional connectivity;functional magnetic resonance imaging;gender;gray matter;human;human tissue;male;memory;mild cognitive impairment;questionnaire;rest;validation process;white matter;biological marker,"Franzmeier, N.;Caballero, M. Á A.;Taylor, A. N. W.;Simon-Vermot, L.;Buerger, K.;Ertl-Wagner, B.;Mueller, C.;Catak, C.;Janowitz, D.;Baykara, E.;Gesierich, B.;Duering, M.;Ewers, M.;For The Alzheimer’, S. Disease Neuroimaging Initiative",2016,,10.1007/s11682-016-9599-1,0,
4336,Novel Compound Heterozygous Spatacsin Mutations in a Greek Kindred with Hereditary Spastic Paraplegia SPG11 and Dementia,"SPG11 belongs to the autosomal recessive hereditary spastic paraplegias (HSP) and presents during childhood or puberty with a complex clinical phenotype encompassing learning difficulties, ataxia, peripheral neuropathy, amyotrophy, and mental retardation. We hereby present the case of a 30-year-old female patient with complex autosomal recessive HSP with thinning of the corpus callosum (TCC) and dementia that was compound heterozygous with two novel mutations in the SPG11 gene. Sequence analysis of the SPG11 gene revealed two novel mutations in a compound heterozygous state in the index patient (c.2431C>T/p.Gln811Ter and c.6755_6756insT/p.Glu2252Aspfs*88). MRI showed abnormal TCC, white matter (WM) hyperintensities periventricularly, and the 'ears of the lynx' sign. Diffusion tensor imaging showed a mild-to-moderate decrease in fractional anisotropy and an increase in mean diffusivity in WM compared to age-matched controls, while magnetic resonance spectroscopy showed abnormal findings in affected WM with a decrease in N-acetyl-aspartate in WM regions of interest. This is the first SPG11 kindred from the Greek population to be reported in the medical literature.",,"Fraidakis, M. J.;Brunetti, M.;Blackstone, C.;Filippi, M.;Chio, A.",2016,,10.1159/000444715,0,
4337,Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor,Sixteen affected individuals are described from two families with early onset autosomal dominant familial Alzheimer's disease. A mutation at codon 139 in the presenilin 1 gene on chromosome 14 results in a methionine to valine substitution which cosegregates with the disease in these families. Onset of dementia was before the age of 50 years in all individuals. The ages at onset within each family were tightly clustered but were significantly different between the families; this difference could not be accounted for by apolipoprotein E status and suggests the existence of a further genetic factor that modifies age at disease onset. The pattern of cognitive decline was similar in both families: early memory loss (initially selective for verbal memory in some individuals) was followed soon after by loss of arithmetic skills while naming and object perception skills were relatively preserved. A speech production deficit was observed in three members of one family but not in the other. Seizures were common and usually predated by myoclonic jerks by a number of years. Serial MRIs showed progressive cortical atrophy with periventricular white matter change appearing 3-4 years into the disease. PET revealed parieto-temporal hypometabolism in all individuals scanned. The diagnosis of Alzheimer's disease was confirmed with typical histopathology in one individual from each family.,adult;Alzheimer disease;amnesia;article;chromosome 14;cognition;gene;gene location;human;nuclear magnetic resonance imaging;priority journal;verbal memory,"Fox, N. C.;Kennedy, A. M.;Harvey, R. J.;Lantos, P. L.;Roques, P. K.;Collinge, J.;Hardy, J.;Hutton, M.;Stevens, J. M.;Warrington, E. K.;Rossor, M. N.",1997,,,0,
4338,Role of hippocampal CA1 atrophy in memory encoding deficits in amnestic Mild Cognitive Impairment,"Identifying the specific substrates of memory deficits in early Alzheimer's disease would help to develop clinically-relevant therapies. The present study assesses the relationships between encoding versus retrieval deficits in patients with amnestic Mild Cognitive Impairment (aMCI) and atrophy specifically within the hippocampus and throughout the white matter. Twenty-two aMCI patients underwent T1-weighted MRI scans and neuropsychological testing. Grey matter and white matter segments obtained from the MRI images were each entered in correlation analyses, assessed only in the hippocampus for grey matter segments, with encoding and retrieval memory performances. For the grey matter segments, the resulting spmT correlation maps were then superimposed onto a 3D surface view of the hippocampus to identify the relative involvement of the different subfields, a method already used and validated elsewhere. Memory encoding deficits specifically correlated with CA1 subfield atrophy, while no relationship was found with white matter atrophy. In contrast, retrieval deficits were weakly related to hippocampal atrophy and did not involve a particular subfield, while they strongly correlated with loss of white matter, specifically in medial parietal and frontal areas. In aMCI patients, encoding impairment appears specifically related to atrophy of the CA1 hippocampal subfield, consistent with the predominance of encoding deficits and CA1 atrophy in aMCI. In contrast, episodic retrieval deficits seem to be underlain by more distributed tissue losses, consistent with a disruption of a hippocampo-parieto-frontal network.",Aged;Atrophy;Female;Hippocampus/ pathology/ physiopathology;Humans;Male;Memory Disorders/ physiopathology;Mild Cognitive Impairment/ physiopathology,"Fouquet, M.;Desgranges, B.;La Joie, R.;Riviere, D.;Mangin, J. F.;Landeau, B.;Mezenge, F.;Pelerin, A.;de La Sayette, V.;Viader, F.;Baron, J. C.;Eustache, F.;Chetelat, G.",2012,Feb 15,10.1016/j.neuroimage.2011.11.036,0,
4339,Cortical atrophy in patients with cerebral amyloid angiopathy: A case-control study,"Background: Loss of cortical grey matter is a diagnostic marker of many neurodegenerative diseases, and is a key mediator of cognitive impairment. We postulated that cerebral amyloid angiopathy (CAA), characterised by cortical vascular amyloid deposits, is associated with cortical tissue loss independent of parenchymal Alzheimer's disease pathology. We tested this hypothesis in patients with hereditary cerebral haemorrhage with amyloidosis-Dutch type (HCHWA-D), a monogenetic disease with minimal or no concomitant Alzheimer's disease pathology, as well as in patients with sporadic CAA and healthy and Alzheimer's disease controls. Methods: In this observational case-control study, we included six groups of participants: patients diagnosed with HCHWA-D using genetic testing; healthy controls age-matched to the HCHWA-D group; patients with probable sporadic CAA without dementia; two independent cohorts of healthy controls age-matched to the CAA group; and patients with Alzheimer's disease age-matched to the CAA group. De-identified (but unmasked) demographic, clinical, radiological, and genetic data were collected at Massachusetts General Hospital (Boston, MA, USA), at Leiden University (Leiden, Netherlands), and at sites contributing to Alzheimer's Disease Neuroimaging Initiative (ADNI). The primary outcome measure was cortical thickness. The correlations between cortical thickness and structural lesions, and blood-oxygen-level-dependent time-to-peak (BOLD-TTP; a physiological measure of vascular dysfunction) were analysed to understand the potential mechanistic link between vascular amyloid and cortical thickness. The radiological variables of interest were quantified using previously validated computer-assisted tools, and all results were visually reviewed to ensure their accuracy. Results: Between March 15, 2006, and Dec 1, 2014, we recruited 369 individuals (26 patients with HCHWA-D and 28 age-matched, healthy controls; 63 patients with sporadic CAA without dementia; two healthy control cohorts with 63 and 126 individuals; and 63 patients with Alzheimer's disease). The 26 patients with HCHWA-D had thinner cortices (2·31 mm [SD 0·18]) than the 28 healthy controls (mean difference -0·112 mm, 95% CI -0·190 to -0·034, p=0·006). The 63 patients with sporadic CAA without dementia had thinner cortices (2·17 mm [SD 0·11]) than the two healthy control cohorts (n=63, mean difference -0·14 mm, 95% CI -0·17 to -0·10, p<0·0001; and n=126, -0·10, -0·13 to -0·06, p<0·0001). All differences remained independent in multivariable analyses. The 63 patients with Alzheimer's disease displayed more severe atrophy than the patients with sporadic CAA (2·1 mm [SD 0·14], difference 0·07 mm, 95% CI 0·11 to 0·02, p=0·005). We found strong associations between cortical thickness and vascular dysfunction in the patients with HCHWA-D (ρ=-0·58, p=0·003) or sporadic CAA (r=-0·4, p=0·015), but not in controls. Vascular dysfunction was identified as a mediator of the effect of hereditary CAA on cortical atrophy, accounting for 63% of the total effect. Interpretation: The appearance of cortical thinning in patients with HCHWA-D indicates that vascular amyloid is an independent contributor to cortical atrophy. These results were reproduced in patients with the more common sporadic CAA. Our findings also suggest that CAA-related cortical atrophy is at least partly mediated by vascular dysfunction. Our results also support the view that small vessel diseases such as CAA can cause cortical atrophy even in the absence of Alzheimer's disease, a conclusion that can help radiologists, neurologists, and other clinicians who diagnose these common geriatric conditions. Funding: National Institutes of Health.",adult;aged;Alzheimer disease;article;BOLD signal;brain atrophy;brain cortex atrophy;brain hemorrhage;case control study;controlled study;cortical thickness (brain);disease association;disease severity;female;functional magnetic resonance imaging;hereditary cerebral hemorrhage with amyloidosis Dutch type;human;leukoaraiosis;major clinical study;male;middle aged;monogenic disorder;observational study;priority journal;sporadic cerebral amyloid angiopathy;vascular amyloidosis,"Fotiadis, P.;van Rooden, S.;van der Grond, J.;Schultz, A.;Martinez-Ramirez, S.;Auriel, E.;Reijmer, Y.;van Opstal, A. M.;Ayres, A.;Schwab, K. M.;Hedden, T.;Rosand, J.;Viswanathan, A.;Wermer, M.;Terwindt, G. M.;Sperling, R. A.;Polimeni, J. R.;Johnson, K. A.;van Buchem, M. A.;Greenberg, S. M.;Gurol, M. E.",2016,,,0,
4340,Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD,"OBJECTIVE: To test the hypotheses 1) that whole-brain volume decline begins in early adulthood, 2) that cross-sectional and longitudinal atrophy estimates agree in older, nondemented individuals, and 3) that longitudinal atrophy accelerates in the earliest stages of Alzheimer disease (AD). METHODS: High-resolution, high-contrast structural MRIs were obtained from 370 adults (age 18 to 97). Participants over 65 (n = 192) were characterized using the Clinical Dementia Rating (CDR) as either nondemented (CDR 0, n = 94) or with very mild to mild dementia of the Alzheimer type (DAT, CDR 0.5 and 1, n = 98). Of these older participants, 79 belonged to a longitudinal cohort and were imaged again a mean 1.8 years after baseline. Estimates of gray matter (nGM), white matter (nWM), and whole-brain volume (nWBV) normalized for head sizes were generated based on atlas registration and image segmentation. RESULTS: Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss. Whole-brain volume differences were detected by age 30. The cross-sectional atrophy model overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In those individuals with very mild DAT, atrophy rate more than doubled (-0.98% per year). CONCLUSIONS: Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.","Adolescent;Adult;Age Factors;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ diagnosis/physiopathology;Atrophy/ diagnosis/physiopathology;Brain/ pathology/physiopathology;Brain Mapping;Disease Progression;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging/standards;Male;Middle Aged;Reference Values;Regression Analysis","Fotenos, A. F.;Snyder, A. Z.;Girton, L. E.;Morris, J. C.;Buckner, R. L.",2005,Mar 22,10.1212/01.wnl.0000154530.72969.11,0,
4341,Cross-sectional and longitudinal brain-volume decline in aging and AD,"Structural MRI was used to estimate rates of gray matter, white matter, and whole-brain volume decline in normal aging and Alzheimer s Disease (AD), based on a combination of cross-sectional and longitudinal sampling of 370 individuals age 18 to 97. Hierarchical regression of whole-brain volume estimates normalized for head-size from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of white-matter than gray-matter loss. Whole-brain volume differences were detected by age 30. Estimates of volume decline predicted from the cross-sectional sample overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In serially scanned individuals with very mild to mild dementia of the Alzheimer type, atrophy rate more than doubled (-0.98% per year). These and related findings are discussed in terms of a multiple factor framework of aging and AD.",adult;adulthood;aged;aging;Alzheimer disease;article;brain size;cardiovascular risk;cephalometry;cognitive defect;dementia;disease course;disease severity;gray matter;human;lifespan;longitudinal study;major clinical study;neurologic disease;nuclear magnetic resonance imaging;prediction;prevalence;volumetry;white matter,"Fotenos, A. F.;Buckner, R. L.",2006,,,0,
4342,Brain atrophy in normal ageing and Alzheimer's disease volumetric discrimination and clinical correlations,"Background. We examined the differences in volume of the ventricular and extracerebral cerebrospinal fluid spaces in normal ageing and in probable Alzheimer's disease (AD) and we tried to investigate the effects of the severity of illness on the morphometric differentiation of AD and ageing, the principal components underlying brain atrophy in both conditions, and the correlations of these measurements with clinical findings. Method. Forty patients with probable AD were matched with 40 non-demented elderly controls. Both groups underwent standardised clinical tests and unenhanced cranial computed tomography for post hoc volumetric analysis. Results. The lateral and third ventricles and the anterior and lateral fissures were significantly larger in AD than in normal ageing. The volumes of the lateral ventricle and lateral fissure permitted a highly efficient differentiation between normal ageing and AD even at the mild stage of dementia, and this differentiation was improved further in the more severe stages of illness. We identified one principal component underlying brain atrophy in normal ageing and two components in AD: a 'grey matter' component accounting for sulcal and third ventricular enlargement, and a 'white matter' component for lateral ventricular enlargement. In AD, most of the volumetric measurements were significantly correlated with cognitive impairment, but in the group of non- demented elderly controls they were correlated with age. Conclusion. Volumetric indices of brain atrophy permit a highly efficient differentiation between normal ageing and AD even in the mild stages of illness and this demonstrates that substantial structural brain changes have developed in the preclinical phase of illness. We suggest that there is an uncoupling between lateral ventricular enlargement and cortical brain atrophy in AD.",adult;aged;Alzheimer disease;article;brain atrophy;clinical article;cognitive defect;computer assisted tomography;controlled study;dementia;disease severity;female;gray matter;human;male;surgical anatomy;white matter,"Forstl, H.;Zerfass, R.;Geiger-Kabisch, C.;Sattel, H.;Besthorn, C.;Hentschel, F.",1995,,,0,
4343,Neurological disorders in 166 patients with basal ganglia calcification: a statistical evaluation,"Patients investigated at our institute during the last decade included 166 (1.2%) who showed uni- or bilateral basal ganglia calcification on computed tomography. We tested the significance of this neuroradiological observation by statistical comparison of these patients' clinical disorders with the findings in a random sample of 622 patients without basal ganglia calcification. The odds for the most common neurological disturbances were similar in patients with and without basal ganglia calcification. After adjustment for differences in age and brain atrophy there was no evidence of a significantly increased risk of dementia (odds ratio 1.1), cerebral infarction (1.4), epilepsy (0.9), vertigo (1.6), headache (1.8), or alcoholism (0.9), which represented the most common diagnoses. We conclude that basal ganglia calcification cannot be considered as a clinically relevant neuroradiological finding in the majority of cases and that it should not be used as an explanation for frequently observed neurological disturbances.","Basal Ganglia Diseases/*epidemiology/radiography;Calcinosis/*epidemiology/radiography;Comorbidity;Humans;Mental Disorders/epidemiology;Nervous System Diseases/*epidemiology;Odds Ratio;Prevalence;Risk;Tomography, X-Ray Computed","Forstl, H.;Krumm, B.;Eden, S.;Kohlmeyer, K.",1992,Jan,,0,
4344,Quantitative CT scan analysis in senile dementia of the Alzheimer type: II. Radioattentuation of grey and white matter,"The radiodensity of the total intracranial area and of the dorsomedial thalamic nuclei were significantly lower in 60 patients with moderate to severe dementia of the Alzheimer type (DAT) compared to 30 healthy age- and sex-matched controls (p < 0.02). The radiodensity of the caudate nuclei was similar in the DAT and the control group. Frontal and parietal white matter showed only a mild decrease of tissue density in dementia. In DAT these effects did not exhibit significant correlations with age, duration of illness or global cognitive impairment. The densitometric parameters discriminated 78.4% of patients and controls, together with the planimetric measurements 84.4% of the individuals were classified correctly. A potential contribution of white matter shrinkage to 'cortical atrophy' and the possible role of thalamic degeneration in DAT are briefly discussed.",aged;aging;Alzheimer disease;article;attenuation;brain cortex atrophy;brain degeneration;caudate nucleus;cognitive defect;computer assisted tomography;controlled study;disease duration;female;gray matter;human;major clinical study;male;radiodensitometry;senile dementia;thalamus dorsomedial nucleus;white matter,"Forstl, H.;Burns, A.;Lacoby, R.;Eagger, S.;Levy, R.",1991,,,0,
4345,"Psychiatric, neurological and medical aspects of misidentification syndromes: A review of 260 cases","Two hundred and sixty case reports of misidentification syndromes were evaluated. One hundred and seventy-four patients had a Capgras syndrome misidentifying other persons, 18 a Fregoli syndrome, 11 intermetamorphosis, 17 reduplicative paramnesia and the rest had other forms or combinations of mistaken identification. Schizophrenia (127 cases), mostly of paranoid type, affective disorder (29), and organic mental syndromes including dementia (46) were the most common diagnoses in patients who misidentified others or themselves. The patients with reduplicative paramnesia more frequently suffered from head trauma or cerebral infarction and showed more features of right hemisphere lesions on neuropsychological testing or CT scan than the patients with other misidentification syndromes. Forty-one case-reports implicated underlying medical conditions. Forty-six of the patients were reported to show violent behaviour. The misidentification of persons can be a manifestation of any organic or functional psychosis, but the misidentification of place is frequently associated with neurological diseases, predominantly of the right hemisphere. Misidentification syndromes show a great degree of overlap and do not represent distinctive syndromes nor can they be regarded as an expression of a particular disorder. These patients deserve special diagnostic and therapeutic attention because of the possible underlying disorders and their potentially dangerous behaviour.",adult;article;brain infarction;Capgras syndrome;clinical feature;dementia;female;fregoli syndrome;head injury;human;major clinical study;male;neurologic disease;neuropsychiatry;organic psychosyndrome;paranoid schizophrenia;priority journal;psychologic test;reduplicative paramnesia;schizophrenia;syndrome;syndrome delineation;violence,"Forstl, H.;Almeida, O. P.;Owen, A. M.;Burns, A.;Howard, R.",1991,,,0,
4346,Capgras delusion in the elderly: The evidence for a possible organic origin,"We report the case of a 77-year-old right-handed woman with early dementia of the Alzheimer type who developed the paranoid delusion that her husband had been replaced by an imposter (Capgras phenomenon). Her CT scan showed mild generalized cortical atrophy and a marked atrophy of the parieto-occipital cortex. We reviewed the cases of 45 patients over 60 years who showed a Capgras delusion. Twenty-five suffered from dementia or other chronic organic mental disorders, 20 were paranoid, 14 were at least moderately depressed and 12 disorientated. CT scans (reported in 17 cases) showed global cerebral atrophy in 12 patients. Right hemisphere infarcts have been described in two elderly patients with Capgras delusions. Focal brain atrophy in Alzheimer type dementia has hitherto not been reported in association with this delusional symptom. We conclude from these observations that marked cerebral lesions and specific neuropsychological deficits are not required for the development of the Capgras phenomenon, which can occur in various functional or organic psychosis of old age.",carbamazepine;clomipramine;aged;article;atrophy;brain injury;Capgras syndrome;case report;computer assisted tomography;delusion;dementia;female;hemisphere;human;mental disease;organic brain syndrome;paranoia;psychosis;symptom,"Forstl, H.;Almeida, O. P.;Iacoponi, E.",1991,,,0,
4347,How to identify stroke mimics in patients eligible for intravenous thrombolysis?,"Since decision-making for thrombolysis in acute stroke settings is restricted to a limited time window and based on clinical assessment and CT findings only, thrombolysis is sometimes applied to patients with a final diagnosis other than a stroke. From a prospectively collected stroke/MRI data bank (2004-2010) with 648 suspected ischemic stroke patients treated with rtPA, we identified patients without evidence of acute infarction on follow-up MRI and a final diagnosis other than a stroke or acute cerebrovascular event. We compared demographics, symptoms, complications, and outcome of patients with stroke mimics (SM) to those with acute infarction. In 42 patients, an SM was diagnosed: seizures in 20, conversion disorder in seven, dementia in six, migraine in three, brain tumor in two, and others in four patients. Patients with SM less often had typical stroke symptoms like dysarthria (p<0.01), facial palsy (p<0.001), hemiparesis (p< 0.001), horizontal gaze palsy (p<0.001), and visuospatial neglect (p = 0.03), while aphasia (p = 0.004) and accompanying convulsions (p = 0.01) occurred more often. Independent predictors of SM were known cognitive impairment, aphasia, and accompanying convulsions. Thrombolysis-related complications (orolingual angioedema) occurred in one SM patient and none of the SM patients deteriorated clinically. Stroke mimics comprise neurological/psychiatric disorders and differ from ischemic stroke patients with regard to the clinical presentation at onset. This might be helpful in deciding which patients should undergo acute stroke MRI to rule out SM, facilitate treatment decisions, and reduce the risk of unnecessary therapy. © Springer-Verlag 2011.",alteplase;adult;aged;aphasia;article;blood clot lysis;brain infarction;brain ischemia;brain tumor;convulsion;demography;disorientation;dysarthria;facial nerve paralysis;female;fibrinolytic therapy;follow up;gaze paralysis;headache;human;major clinical study;male;medical decision making;mental disease;migraine;neuroimaging;nuclear magnetic resonance imaging;priority journal;prospective study;seizure;cerebrovascular accident;stroke mimic;visual field defect,"Förster, A.;Griebe, M.;Wolf, M. E.;Szabo, K.;Hennerici, M. G.;Kern, R.",2012,,,0,
4348,Demyelination of superficial white matter in early Alzheimer's disease: a magnetization transfer imaging study,"Assuming selective vulnerability of short association U-fibers in early Alzheimer's disease (AD), we quantified demyelination of the surface white matter (dSWM) with magnetization transfer ratio (MTR) in 15 patients (Clinical Dementia Rating Scale [CDR] 0.5-1; Functional Assessment Staging [FAST]: 3-4) compared with 15 controls. MTRs were computed for 39 areas in each hemisphere. We found a bilateral MTR decrease in the temporal, cingulate, parietal, and prefrontal areas. With linear discriminant analysis, we successfully classified all the participants with 3 variates including the cuneus, parahippocampal, and superior temporal regions of the left hemisphere. The pattern of dSWM changed with the age of AD onset. In early onset patients, we found bilateral posterior demyelination spreading to the temporal areas in the left hemisphere. The late onset patients showed a distributed bilateral pattern with the temporal and cingulate areas strongly affected. A correlation with Mini Mental State Examination (MMSE), Lexis, and memory tests revealed the dSWM impact on cognition. A specific landscape of dSWM in early AD shows the potential of MTR imaging as an in vivo biomarker superior to currently used techniques.","Aged;Alzheimer Disease/ complications/ pathology;Demyelinating Diseases/ complications/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Fornari, E.;Maeder, P.;Meuli, R.;Ghika, J.;Knyazeva, M. G.",2012,Feb,10.1016/j.neurobiolaging.2010.11.014,0,
4349,Clinical and instrumental diagnosis of Alzheimer's and multi-infarct dementia,"We investigated the possible correlation between functional and anatomical imaging techniques and clinical exams in patients with Alzheimer's and vascular dementia. We examined 24 patients affected with dementia, 16 of them with Alzheimer's disease. 7 with multiinfarct and 1 with mixed dementia. All patients were submitted to clinical, morphological (MRI, CT) and functional (SPECT, cerebral flowmetry) studies. The severity of hypoperfusion revealed by SPECT was highly correlated with cognitive impairment in Alzheimer's dementia patients. The abnormal perfusion was mostly bilateral, in the temporal-parietal region, and involved the frontal regions only in the most severe cases. CT and especially MRI showed aspecific cortical and subcortical atrophy, most evident in the medial temporal region. In the patients with multiinfarct dementia, the hypoperfused cortical regions revealed by SPECT were sometimes related to vascular lesions proved at MRI and CT. In the patients with multiinfarct dementia, MRI showed more or less apparent white matter lesions referrable to ischemic insult, besides cortical and subcortical atrophy. MRI allows a differential diagnosis between these two cerebral pathologic conditions of aging. Cerebral flowmetry by Xenon 133 inhalation showed reduced cerebral blood flow in both dementia types. In Alzheimer patients, regional flow was reduced especially in the posterior parietal regions. In multiinfarct dementia patients, flow was more diffusely reduced and asymmetrical. Brain function imaging appears to yield useful information for the differential diagnosis in the most common dementia syndromes. Since the neuropathologic data from brain biopsy are rarely available, clinical and instrumental findings must be integrated for diagnostic and pathogenetic insights of the diseases causing cognitive impairment.",,"Fornarelli, D.;Ascoli, G.;Rossi, R.;Manca, A.;Lanza, R.;Moretti, V.;Scarpino, O.;Guidi, M.",1996,1996,,0,
4350,Genome-wide association studies of cerebral white matter lesion burden,"Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p (discovery) = 4.0 × 10(-9); p(replication) = 1.3 × 10(-7); p(combined) = 4.0 × 10 (-15)). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9)), rs11869977 (p = 5.7 × 10(-9)), rs936393 (p = 6.8 × 10(-9)), rs3744017 (p = 7.3 × 10(-9)), and rs1055129 (p = 4.1 × 10(-8)). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. Copyright © 2011 American Neurological Association.",,"Fornage, M.;Debette, S.;Bis, J. C.;Schmidt, H.;Ikram, M. A.;Dufouil, C.;Sigurdsson, S.;Lumley, T.;Destefano, A. L.;Fazekas, F.;Vrooman, H. A.;Shibata, D. K.;Maillard, P.;Zijdenbos, A.;Smith, A. V.;Gudnason, H.;De Boer, R.;Cushman, M.;Mazoyer, B.;Heiss, G.;Vernooij, M. W.;Enzinger, C.;Glazer, N. L.;Beiser, A.;Knopman, D. S.;Cavalieri, M.;Niessen, W. J.;Harris, T. B.;Petrovic, K.;Lopez, O. L.;Au, R.;Lambert, J. C.;Hofman, A.;Gottesman, R. F.;Garcia, M.;Heckbert, S. R.;Atwood, L. D.;Catellier, D. J.;Uitterlinden, A. G.;Yang, Q.;Smith, N. L.;Aspelund, T.;Romero, J. R.;Rice, K.;Taylor, K. D.;Nalls, M. A.;Rotter, J. I.;Sharrett, R.;Van Duijn, C. M.;Amouyel, P.;Wolf, P. A.;Gudnason, V.;Van Der Lugt, A.;Boerwinkle, E.;Psaty, B. M.;Seshadri, S.;Tzourio, C.;Breteler, M. M. B.;Mosley, T. H.;Schmidt, R.;Longstreth, W. T.;Decarli, C.;Launer, L. J.",2011,June,,0,
4351,Age-related changes in brain energetics and phospholipid metabolism,"Evidence suggests that mitochondria undergo functional and morphological changes with age. This study aimed to investigate the relationship of brain energy metabolism to healthy aging by assessing tissue specific differences in metabolites observable by phosphorus (31P) MRS. 31P MRSI at 4 Tesla (T) was performed on 34 volunteers, aged 21-84, screened to exclude serious medical and psychiatric diagnoses. Linear mixed effects models were used to analyze the effects of age on phosphorus metabolite concentrations, intracellular magnesium and pH estimates in brain tissue. A significant age associated decrease in brain pH (S0.53% per decade), increase in PCr (1.1% per decade) and decrease in PME (1.7% per decade) were found in total tissue, with PCr effects localized to the gray matter. An increase in beta NTP as a function of age (1% per decade) approached significance (p = 0.052). There were no effects demonstrated with increasing age for intracellular magnesium, PDE or inorganic phosphate. This study reports the effects of healthy aging on brain chemistry in the gray matter versus white matter using 31P MRS measures of high energy phosphates, pH and membrane metabolism. Increased PCr, increased beta NTP (reflecting ATP) and reduced pH may reflect altered energy production with healthy aging. Unlike some previous studies of aging and brain chemistry, this study examined healthy, non-demented and psychiatrically stable older adults and specifically analyzed gray-white matter differences in brain metabolism. Copyright © 2009 John Wiley & Sons, Ltd.",magnesium;phosphate;phosphorus;adult;aged;aging;article;brain level;clinical article;controlled study;energy transfer;energy yield;female;gray matter;human;male;pH measurement;phospholipid metabolism;phosphorus nuclear magnetic resonance;priority journal;screening;white matter,"Forester, B. P.;Berlow, Y. A.;Harper, D. G.;Jensen, J. E.;Lange, N.;Froimowitz, M. P.;Ravichandran, C.;Iosifescu, D. V.;Lukas, S. E.;Renshaw, P. F.;Cohen, B. M.",2010,,,0,
4352,Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism,"BACKGROUND: The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure. METHODS: To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography. RESULTS: Morphological analysis revealed an ""inverted-U"" shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles. CONCLUSION: In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression.","Adolescent;Adult;Alleles;Brain/*anatomy & histology;Brain-Derived Neurotrophic Factor/*genetics;Diffusion Tensor Imaging;Female;Genotype;Heterozygote;Homozygote;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;*Polymorphism, Single Nucleotide;Young Adult;Bdnf;Diffusion;Intrinsic curvature;Mri;Structural;Val66met","Forde, N. J.;Ronan, L.;Suckling, J.;Scanlon, C.;Neary, S.;Holleran, L.;Leemans, A.;Tait, R.;Rua, C.;Fletcher, P. C.;Jeurissen, B.;Dodds, C. M.;Miller, S. R.;Bullmore, E. T.;McDonald, C.;Nathan, P. J.;Cannon, D. M.",2014,Apr 15,10.1016/j.neuroimage.2013.12.050,0,
4353,Progression of small vessel disease correlates with cortical thinning in Parkinson's disease,"OBJECTIVE: Cerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinson's disease (PD), however the pathophysiological role of SVD in PD-dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition. METHODS: Seventy-three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no-progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance. RESULTS: Fourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months. DISCUSSION: The extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD.","Aged;Cerebral Cortex/diagnostic imaging/ pathology;Cerebral Small Vessel Diseases/ complications/diagnostic imaging;Cognition Disorders/ etiology;Disease Progression;Executive Function/physiology;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory Disorders/ etiology;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Parkinson Disease/diagnostic imaging/ pathology;Statistics, Nonparametric;Cortical thinning;Neuroimaging;Parkinson's disease;Small vessels cerebrovascular disease","Foo, H.;Mak, E.;Yong, T. T.;Wen, M. C.;Chander, R. J.;Au, W. L.;Tan, L.;Kandiah, N.",2016,Oct,,0,4354
4354,Progression of small vessel disease correlates with cortical thinning in Parkinson's disease,"OBJECTIVE: Cerebral small-vessel disease (SVD) is a risk factor for dementia in Parkinson's disease (PD), however the pathophysiological role of SVD in PD-dementia is unclear. We investigated the impact of baseline and progression of SVD on cortical thickness and the correlation to cognition. METHODS: Seventy-three mild PD patients with baseline and follow-up structural MRI scans, serial clinical and neuropsychological assessments were studied. SVD included the load of white matter hyperintensities (WMH), lacunes and perivascular spaces (PVS). WMH progression was assessed using the modified Rotterdam Progression scale, while for lacunes and PVS, development of new lesions was considered as lesion progression. Patients were classified as having SVD-progression and SVD-no-progression based on the longitudinal changes in their SVD measures. Freesurfer was used to measure baseline and follow-up regional cortical thickness and subcortical volumes and correlated to cognitive performance. RESULTS: Fourteen patients were classified as SVD-progression and 59 as SVD-no-progression. Over 18 months, PD SVD-progression demonstrated significant cortical thinning in the left frontal and bilateral parietal regions with associated decline in memory, executive function, and motor functions. PD SVD-progression also had reduced volumes in the nucleus accumbens and amygdala at baseline and greater atrophy in the caudate nucleus over 18 months. DISCUSSION: The extent and progression of SVD is associated with focal cerebral atrophy and domain-specific cognitive dysfunction. Measures to retard SVD may be potentially useful in preventing dementia in PD.",Cortical thinning;Neuroimaging;Parkinson's disease;Small vessels cerebrovascular disease,"Foo, H.;Mak, E.;Yong, T. T.;Wen, M. C.;Chander, R. J.;Au, W. L.;Tan, L.;Kandiah, N.",2016,Jun 30,10.1016/j.parkreldis.2016.06.019,0,
4355,Dementia caused by miliary cerebral metastasis of a hepatocarcinoma,"Different types of tumors account for the etiology of 8.6% of all cases of dementia. Cerebral computed tomography (CT) permits the detection of most of them. The miliary metastasis variety commonly presents as dementia, and CT may then be normal. A patient with late epilepsy after cerebral infarction developed subacute dementia and he subsequently died. Post mortem study disclosed miliary cerebral metastases of a clinically unsuspected hepatocarcinoma. Cerebral CT did not detect the metastases. Although the incidence of hepatocarcinoma is increasing, we are unaware of any similar reported case, as cerebral involvement is exceptional in this condition. Despite its rarity, this case highlights the need to perform thorough neuropathological investigations in dementia.",article;brain cortex;brain tumor;case report;computer assisted tomography;dementia;human;liver cell carcinoma;liver tumor;male;metastasis;middle aged;pathology,"Fontán, A.;Zarranz, J. J.;Camarero, C.;Forcadas, I.",1989,,,0,
4356,Dementia in two histologically confirmed cases of multiple sclerosis: One case with isolated dementia and one case associated with psychiatric symptoms,"During the past 10 years, considerable attention has been devoted to cognitive impairment in multiple sclerosis. Occasionally this impairment may be so severe that multiple sclerosis presents as a dementia associated with only minor neurological signs and symptoms. The cases of two women affected by multiple sclerosis who presented with a pure dementia are reported. In the first patient, a progressive apragmatic behavioural disturbance with reduced short term memory and learning abilities were the main clinical features. Neuropathological examination of the brain disclosed numerous plaques in the periventricular white matter, with severe atrophy of the corpus callosum. Plaques were also seen in the white matter of both hippocampus and in the columns of the fornix. The impairment of short term memory could be linked to these lesions. Behavioural changes were probably related to the bilateral lesions of the long associative bundles that disconnected the frontal lobes from other parts of the cerebral hemispheres. In the second patient, visual hallucinations were associated with cognitive dysfunction. MRI showed large plaques in the white matter of both left frontal and temporal lobes. Smaller plaques were also present in the periventricular white matter of the occipital lobes, the nature of which were confirmed by a stereotactic biopsy.",adult;article;behavior disorder;brain injury;case report;clinical feature;cognitive defect;dementia;female;frontal lobe;histology;human;learning disorder;mental disease;multiple sclerosis;neuropathology;nuclear magnetic resonance imaging;priority journal;short term memory;temporal lobe;visual hallucination;white matter,"Fontaine, B.;Seilhean, D.;Tourbah, A.;Daumas-Duport, C.;Duyckaerts, C.;Benoit, N.;Devaux, B.;Hauw, J. J.;Rancurel, G.;Lyon-Caen, O.",1994,,,0,
4357,Functional expressions of the aging brain,"In the conventional view, aging of the brain is associated with atrophy vascular abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging is associated with slowing of processing and memory loss. However, many studies of aging do not examine the cases to exclude demented people. The nutrition and memory in the homebound elderly study (NAME) excluded cases clinically diagnosed as having dementia. Cortical atrophy based on MRI ratings was significantly correlated with vascular disease, white matter hyperintensities, processing speed, and memory but not hippocampus and amygdala volume. Renal function and homocysteine were also associated with cortical atrophy but not with the cognitive variables. In conclusion, brain atrophy of aging in the absence of dementia is related to vascular disease but not hippocampal atrophy. Studies of nutritional interventions should consider using MRI atrophy rather than cognition as outcome. © 2010 International Life Sciences Institute.",homocysteine;adrenal cortex atrophy;amygdaloid nucleus;article;brain atrophy;cerebrospinal fluid;cognition;dementia;disease association;hippocampus;human;kidney function;memory;nuclear magnetic resonance imaging;nutrition;protein expression;vascular disease,"Folstein, M.;Folstein, S.",2010,,,0,
4358,Rating scales and computed tomography in multi-infarct dementia,"Forty patients who fulfilled the DSM-III-R criteria for multi-infarct dementia and had a score of 7 points or more on Hachinski ischemia score (HIS) were analyzed with the purpose to correlate the rating scales and CT scans. Among the examined patients there were 32 women with the average age of 68.5 +/- 9.8 years and 8 men with the average age of 68.8 +/- 10.4 years. No significant difference between sex in relation to Folstein Mini-mental state examination (MMSE), Gottfries-Brane-Steen scale (GBS) and Sandoz clinical assessment-geriatric scale (SCAG) was found. There is no correlation of GBS and SCAG on MMSE. With regression analysis a good correlation was found between GBS and SCAG, and we suggest that in such studies only one of these two scales is sufficient. CT abnormalities were found in about 77% of examined patients without difference according to sex. But, GBS score demonstrated greater disability among MID patients with abnormal CT scans than in MID patients with normal CT scans. In medical history of male MID patients completed stroke was significantly more common than among women, while the female MID patients had in their history significantly more frequent transient ischemic attack (TIA). This finding should be checked in a greater patient population. It is stressed that in everyday clinical practice it is necessary to use the diagnosis of multi-infarct dementia, e.g. to differentiate cerebral diseases according to etiology and pathogenesis.","Aged;Aged, 80 and over;Brain/radiography;Cerebrovascular Disorders/radiography;Dementia, Multi-Infarct/*diagnosis/psychology/radiography;Female;Humans;Male;Middle Aged;Psychiatric Status Rating Scales;*Tomography, X-Ray Computed","Folnegovic-Smalc, V.;Mimica, N.;Makaric, G.;Loos, V.;Kittner, B.;Mimica, N.",1992,,,0,
4359,Interactive effects of apolipoprotein E4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults,"Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A1c/fasting glucose and APOE4 on FA for all later myelinating WM regions but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup. © The Author(s) 2013.",,"Foley, J. M.;Salat, D. H.;Stricker, N. H.;Zink, T. A.;Grande, L. J.;McGlinchey, R. E.;Milberg, W. P.;Leritz, E. C.",2014,May,,0,
4360,Characterization of PiB binding to white matter in Alzheimer disease and other dementias,"(11)C-Pittsburgh Compound B ((11)C-PiB) PET has demonstrated significantly higher PiB retention in the gray matter of Alzheimer disease (AD) patients than in healthy controls (HCs). PiB is similarly retained within the white matter of HC and AD brains. Although the specificity of PiB for Ab plaques in gray matter has been well described, the nature of PiB binding to white matter remains unclear. In this study, we characterized the binding of PiB to human white matter homogenates. Methods: In vitro binding studies were conducted using (3)H-PiB (0.1-500 nM) and white matter brain homogenates (100 μg) from 3 AD patients and 3 HCs. Nonspecific binding was determined using PiB (1 μM). White matter from the same patients was also analyzed by immunofluorescence/immunohistochemistry (IF/IHC) microscopy and Western blotting for Aβ expression. White matter kinetics were also characterized in vivo through (11)C-PiB PET studies in 27 HCs and 34 patients with dementia. IF/IHC experiments were conducted on 1 postmortem patient with dementia, to compare with the (11)C-PiB distribution volume ratio data acquired 23 mo earlier. Results: In vitro saturation studies indicated that (3)H-PiB binds nonspecifically to white matter brain homogenates. PiB fluorescence staining of AD and HC brain sections was consistent with absence of Aβ in IHC staining. Higher gray matter-to-white matter ratios were observed in IHC images than in (11)C-PiB PET images. Conclusion: These studies suggest that PiB binding to white matter is mainly nonsaturable and nonspecific and that PiB retention in the (11)C-PiB PET studies is largely attributable to slower PiB white matter kinetics. Copyright © 2009 by the Society of Nuclear Medicine, Inc.",,"Fodero-Tavoletti, M. T.;Rowe, C. C.;McLean, C. A.;Leone, L.;Li, Q. X.;Masters, C. L.;Cappai, R.;Villemagne, V. L.",2009,1,,0,
4361,Encephalopathy in AIDS patients: evaluation with MR imaging,"The presence and extent of encephalopathy were evaluated in 47 patients with AIDS or AIDS-related complex (ARC) by the use of MR imaging. Twenty-nine (62%) of the patients showed some form of white matter disease, exhibited as high signal intensity on T2-weighted images. Focal white matter lesions were seen in 23 (49%) of the patients, while a diffuse white matter process was observed in six patients (13%). Of the 29 patients who had white matter disease on MR scans, 17 (36%) had a suggestion of white matter involvement on an initial CT study. Meanwhile, 12 (26%) of the patients had a normal CT scan on the initial examination. MR findings showed predominant disease in the subinsular and peritrigonal white matter areas. Marked cerebral atrophy was observed in 17 (36%) of 47 patients, cerebellar atrophy in 18 (38%), and brainstem atrophy in seven patients (15%). Pathologic findings showed that toxoplasmosis was present in eight patients (17%), and primary CNS lymphoma was present in three patients (6%). Cryptococcal meningitis was noted in two (4%) of the patients at autopsy, and Mycobacterium tuberculosis was seen in one (2%) of the patients at autopsy. MR imaging has been shown to be a valuable technique for the detection of encephalopathy in AIDS patients.",AIDS Dementia Complex/ diagnosis;Adult;Brain/pathology;Brain Neoplasms/diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Opportunistic Infections/diagnosis;Retrospective Studies,"Flowers, C. H.;Mafee, M. F.;Crowell, R.;Raofi, B.;Arnold, P.;Dobben, G.;Wycliffe, N.",1990,Nov-Dec,,0,
4362,Multiple Spontaneous Cerebral Microbleeds and Leukoencephalopathy in PSEN1-Associated Familial Alzheimer's Disease: Mirror of Cerebral Amyloid Angiopathy?,"Cerebral microbleeds (CMB) might reflect specific underlying vascular pathologies like cerebral amyloid angiopathy (CAA). In the present study we report the gradient-echo MRI pattern of two siblings with P284S PSEN1 mutation. T2* gradient-echo images of the two subjects demonstrated multiple microbleeds in lobar regions. The role and causes of CMB in sporadic Alzheimer's disease (AD) patients have not been clearly established and useful contributions could derive from familial AD studies. Furthermore, since CAA is a potential risk factor for developing adverse events in AD immunization trials, the identification in vivo of CAA through non-invasive MRI methods could be useful to monitoring side effects.",,"Floris, G.;Di Stefano, F.;Cherchi, M. V.;Costa, G.;Marrosu, F.;Marrosu, M. G.",2015,,10.3233/jad-150165,0,
4363,Longitudinal diffusion imaging across the C9orf72 clinical spectrum,"INTRODUCTION: Discrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes. METHODS: Twenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King's college staging system. RESULTS: Widespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King's stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King's stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R. CONCLUSION: Discrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King's stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.","0 (C9orf72 Protein);0 (C9orf72 protein, human);Adult;Amyotrophic Lateral Sclerosis/ diagnosis/diagnostic imaging/genetics;Brain/physiopathology;C9orf72 Protein/ genetics;Diffusion Tensor Imaging/ methods;Disease Progression;Female;Frontotemporal Dementia/ diagnosis/diagnostic imaging/genetics;Humans;Longitudinal Studies;Male;Middle Aged;Neuropsychological Tests/statistics & numerical data;Prospective Studies;Pyramidal Tracts/physiopathology;White Matter","Floeter, M. K.;Danielian, L. E.;Braun, L. E.;Wu, T.",2018,Jan,,0,
4364,White matter structural integrity and trans-cranial Doppler blood flow pulsatility in normal aging,"Cerebrovascular diseases underlie many forms of age-related cognitive impairment and the mechanism linking the two is hypothesized to involve adverse changes in white matter (WM) integrity. Despite being systemic, small vessel disease does not uniformly affect WM. We performed voxel-wise analysis of MRI images to examine the association between fractional anisotropy (FA) — a diffusion tensor measure of WM structural integrity — and pulsatility index (PI) — a trans-cranial Doppler ultrasound measure of abnormal arterial flow — in adults over the age of 70 years who were free of stroke and dementia. We demonstrate that the relation of PI to microstructural changes in WM is artery specific and regional. We identified spatial clusters of significant correlations between elevated PI and reduced FA which cannot be explained by aging, supporting a vascular hypothesis of WM injury. These areas are not limited to the vascular territories of the vessels where PI is assessed, suggesting that the linkage between PI and FA is not likely a function of perfusion per se, but is consistent with injury caused by mechanical wave emanating from pulsating vessel walls.",transcranial doppler;aged;aging;artery blood flow;article;blood flow;brain artery;diffusion tensor imaging;female;fractional anisotropy;human;male;nuclear magnetic resonance imaging;priority journal;pulsatile flow;pulsatility index;transcranial Doppler ultrasonography;voxel based morphometry;white matter;white matter injury,"Fleysher, R.;Lipton, M. L.;Noskin, O.;Rundek, T.;Lipton, R.;Derby, C. A.",2018,,10.1016/j.mri.2017.11.003,0,
4365,Loss of fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals,"IMPORTANCE: Magnetic resonance imaging markers of incipient cognitive decline among healthy elderly individuals have become important for both clarifying the biological underpinnings of dementia and clinically identifying healthy individuals at high risk of cognitive decline. Even though the role of hippocampal atrophy is well known in the later stages of decline, the ability of fornix-hippocampal markers to predict the earliest clinical deterioration is less clear. OBJECTIVES: To examine the involvement of the hippocampus-fornix circuit in the very earliest stages of cognitive impairment and to determine whether the volumes of fornix white matter and hippocampal gray matter would be useful markers for understanding the onset of dementia and for clinical intervention. DESIGN: A longitudinal cohort of cognitively normal elderly participants received clinical evaluations with T1-weighted magnetic resonance imaging and diffusivity scans during repeated visits over an average of 4 years. Regression and Cox proportional hazards models were used to analyze the relationships between fornix and hippocampal measures and their predictive power for incidence and time of conversion from normal to impaired cognition. SETTING: A cohort of community-recruited elderly individuals at the Alzheimer Disease Center of the University of California, Davis. PARTICIPANTS: A total of 102 cognitively normal elderly participants, with an average age of 73 years, recruited through community outreach using methods designed to enhance ethnic diversity. MAIN OUTCOMES AND MEASURES: Our preliminary hypothesis was that fornix white matter volume should be a significant predictor of cognitive decline among normal elderly individuals and that fornix measures would be associated with gray matter changes in the hippocampus. RESULTS: Fornix body volume and axial diffusivity were highly significant predictors (P = .02 and .005, respectively) of cognitive decline from normal cognition. Hippocampal volume was not significant as a predictor of decline but was significantly associated with fornix volume and diffusivity (P = .004). CONCLUSIONS AND RELEVANCE: This could be among the first studies establishing fornix degeneration as a predictor of incipient cognitive decline among healthy elderly individuals. Predictive fornix volume reductions might be explained at least in part by clinically silent hippocampus degeneration. The importance of this finding is that white matter tract measures may become promising candidate biomarkers for identifying incipient cognitive decline in a clinical setting, possibly more so than traditional gray matter measures.","Aged;Aged, 80 and over;Aging/ pathology;Atrophy/pathology;Cognition Disorders/ diagnosis;Cohort Studies;Diffusion Tensor Imaging;Female;Frontal Lobe/ pathology;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Outcome Assessment (Health Care);Predictive Value of Tests;Proportional Hazards Models;Psychiatric Status Rating Scales;Regression Analysis","Fletcher, E.;Raman, M.;Huebner, P.;Liu, A.;Mungas, D.;Carmichael, O.;DeCarli, C.",2013,Nov,10.1001/jamaneurol.2013.3263,0,
4366,Early brain loss in circuits affected by Alzheimer's disease is predicted by fornix microstructure but may be independent of gray matter,"In a cohort of community-recruited elderly subjects with normal cognition at initial evaluation, we found that baseline fornix white matter (WM) microstructure was significantly correlated with early volumetric longitudinal tissue change across a region of interest (called fornix significant ROI, fSROI), which overlaps circuits known to be selectively vulnerable to Alzheimer's dementia pathology. Other WM and gray matter regions had much weaker or non-existent associations with longitudinal tissue change. Tissue loss in fSROI was in turn a significant factor in a survival model of cognitive decline, as was baseline fornix microstructure. These findings suggest that WM deterioration in the fornix and tissue loss in fSROI may be the early beginnings of posterior limbic circuit and default mode network degeneration. We also found that gray matter baseline volumes in the entorhinal cortex and hippocampus predicted cognitive decline in survival models. But since GM regions did not also significantly predict brain-tissue loss, our results may imply a view in which early, prodromal deterioration appears as two quasi independent processes in white and gray matter regions of the limbic circuit crucial to memory.",age distribution;aged;Alzheimer disease;article;brain fornix;brain size;clinical article;connectome;controlled study;corpus callosum;default mode network;educational status;entorhinal cortex;ethnicity;female;gray matter;human;image analysis;longitudinal study;male;neuroimaging;nuclear magnetic resonance imaging;occipital gyrus;parietal gyrus;posterior cingulate;sex difference;thalamus;white matter,"Fletcher, E.;Carmichael, O.;Pasternak, O.;Maier-Hein, K. H.;DeCarli, C.",2014,,,0,
4367,MRI non-uniformity correction through interleaved bias estimation and B-spline deformation with a template,"We propose a template-based method for correcting field inhomogeneity biases in magnetic resonance images (MRI) of the human brain. At each algorithm iteration, the update of a B-spline deformation between an unbiased template image and the subject image is interleaved with estimation of a bias field based on the current template-to-image alignment. The bias field is modeled using a spatially smooth thin-plate spline interpolation based on ratios of local image patch intensity means between the deformed template and subject images. This is used to iteratively correct subject image intensities which are then used to improve the template-to-image deformation. Experiments on synthetic and real data sets of images with and without Alzheimer's disease suggest that the approach may have advantages over the popular N3 technique for modeling bias fields and narrowing intensity ranges of gray matter, white matter, and cerebrospinal fluid. This bias field correction method has the potential to be more accurate than correction schemes based solely on intrinsic image properties or hypothetical image intensity distributions.",Alzheimer disease;article;brain;cerebrospinal fluid;female;human;image quality;male;methodology;nuclear magnetic resonance imaging;radiography,"Fletcher, E.;Carmichael, O.;Decarli, C.",2012,,,0,4368
4368,MRI non-uniformity correction through interleaved bias estimation and B-spline deformation with a template,"We propose a template-based method for correcting field inhomogeneity biases in magnetic resonance images (MRI) of the human brain. At each algorithm iteration, the update of a B-spline deformation between an unbiased template image and the subject image is interleaved with estimation of a bias field based on the current template-to-image alignment. The bias field is modeled using a spatially smooth thin-plate spline interpolation based on ratios of local image patch intensity means between the deformed template and subject images. This is used to iteratively correct subject image intensities which are then used to improve the template-to-image deformation. Experiments on synthetic and real data sets of images with and without Alzheimer's disease suggest that the approach may have advantages over the popular N3 technique for modeling bias fields and narrowing intensity ranges of gray matter, white matter, and cerebrospinal fluid. This bias field correction method has the potential to be more accurate than correction schemes based solely on intrinsic image properties or hypothetical image intensity distributions.",Alzheimer Disease/ radiography;Brain/ radiography;Cerebrospinal Fluid/radiography;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Radiographic Image Enhancement/ methods,"Fletcher, E.;Carmichael, O.;Decarli, C.",2012,,10.1109/embc.2012.6345882,0,
4369,Use of white matter reference regions for detection of change in florbetapir positron emission tomography from completed phase 3 solanezumab trials,"INTRODUCTION: We compared subject-specific white matter (SSWM) and whole cerebellum (CBL) reference regions for power to detect longitudinal change in amyloid positron emission tomography signal. METHODS: Positive florbetapir positron emission tomography scans were analyzed from participants (66 placebo treated and 63 solanezumab treated) with mild dementia caused by Alzheimer's disease from the EXPEDITION and EXPEDITION2 studies. For comparison to CBL, a second normalization was performed on longitudinal data using an SSWM correction factor (SSWM normalization ratio [SSWMnr]). Analysis of covariance assessed baseline to 18-month change between treatment with solanezumab and placebo. Sample and effect size estimations provided magnitude of observed treatment changes. RESULTS: Longitudinal percent change between placebo and solanezumab using CBL was not significant (P = .536) but was significant for SSWMnr (P = .042). Compared with CBL, SSWMnr technique increased the power to detect a treatment difference, more than tripling the effect size and reducing the sample size requirements by 85% to 90%. DISCUSSION: Adjusting longitudinal standardized uptake value ratios with an SSWM reference region in these antiamyloid treatment trials increased mean change detection and decreased variance resulting in the substantial improvement in statistical power to detect change.",Alzheimer's disease;Disease course;Florbetapir;Growth mixture model;Reference region;Serial PET imaging;Solanezumab;Trajectory,"Fleisher, A. S.;Joshi, A. D.;Sundell, K. L.;Chen, Y. F.;Kollack-Walker, S.;Lu, M.;Chen, S.;Devous, M. D., Sr.;Seibyl, J.;Marek, K.;Siemers, E. R.;Mintun, M. A.",2017,Oct,,0,
4370,"Physical activity, motor function, and white matter hyperintensity burden in healthy older adults","Objective: To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Methods: Total daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with totalWMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction withWMH volume were then added to the model. Results: Higher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Total daily activity modified the association between WMH and motor function (p = 0.007). WMH burden was not associated with motor function in persons with high activity (90th percentile). By contrast, higher WMH burden remained associated with lower motor function in persons with average (50th percentile; estimate = 20.304, slope = 20.133) and low (10th percentile; estimate = -1.793, slope = -0.241) activity. Conclusions: Higher levels of physical activity may reduce the effect of WMH burden on motor function in healthy older adults.",actimetry;aged;article;clinical assessment;clinical evaluation;cognition;female;human;image analysis;image processing;male;motor performance;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;physical activity;priority journal;white matter hyperintensity;white matter lesion,"Fleischman, D. A.;Yang, J.;Arfanakis, K.;Arvanitakis, Z.;Leurgans, S. E.;Turner, A. D.;Barnes, L. L.;Bennett, D. A.;Buchman, A. S.",2015,,,0,
4371,The Memory Aid study: protocol for a randomized controlled clinical trial evaluating the effect of computer-based working memory training in elderly patients with mild cognitive impairment (MCI),"BACKGROUND: Mild cognitive impairment (MCI) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging, but less severe than dementia. Reduced working memory (WM) is regarded as one of the core symptoms of an MCI condition. Recent studies have indicated that WM can be improved through computer-based training. The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI, and if cognitive training induces structural changes in the white and gray matter of the brain, as assessed by structural MRI. METHODS/DESIGNS: The proposed study is a blinded, randomized, controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic. The participants will be randomized to either a training program or a placebo version of the program. The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks. The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks. Neuropsychological assessment and structural MRI will be performed before and 1 month after training, and at a 5-month folllow-up. DISCUSSION: If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new, cost-effective treatment for MCI. Secondly, evaluation of any training-induced structural changes to gray or white matter will improve the current understanding of the mechanisms behind effective cognitive interventions in patients with MCI. TRIAL REGISTRATION: ClinicalTrials.gov NCT01991405. November 18, 2013.","Age Factors;Aging [psychology];Clinical Protocols;Cognition;Magnetic Resonance Imaging;Memory;Mild Cognitive Impairment [diagnosis] [psychology] [therapy];Neuropsychological Tests;Norway;Research Design;Therapy, Computer-Assisted;Time Factors;Treatment Outcome;Humans[checkword]","Flak, M. M.;Hernes, S. S.;Skranes, J.;Løhaugen, G. C.",2014,,10.1186/1745-6215-15-156,0,
4372,Neurological deterioration following head injury: The eyes had it,"A 17-year-old male presented with confusion following a mild head injury. Repeated CT scans of the head were normal. There was a 3 year history of decreased vision, associated with a focal pigmentary retinopathy. On assessment he demonstrated visual agnosia and early dementia. An MRI scan showed symmetrical demyelination of the white matter, particularly of the occipital lobes. The diagnosis of subacute sclerosing panencephalitis (SSPE) was confirmed by the typical EEG findings and the presence of measles antibodies in the CSF. The head injury was the precipitating factor which led to a diagnosis of SSPE. This disease should be considered in young patients who have persisting cognitive dysfunction out of keeping with the severity of the initial trauma. A focal pigmentary retinopathy, especially with macular involvement, should also raise the possibility of SSPE, despite the absence of neurological symptoms initially. We report the longest interval to date between the visual symptoms and onset of neurological signs of SSPE.",adolescent;antibody detection;article;case report;cerebral blindness;cerebrospinal fluid examination;demyelinating disease;electroencephalogram;head injury;human;male;nuclear magnetic resonance imaging;priority journal;retina pigment epitheliopathy;retinopathy;subacute sclerosing panencephalitis;traffic accident,"Flaherty, M. P.;O'Flaherty, S. J.",1998,,,0,
4373,Mini-mental state examination is sensitive to brain atrophy in Alzheimer's disease,"BACKGROUND/AIMS: Screening instruments such as the Mini-Mental State Examination (MMSE) are useful for the early identification of Alzheimer's disease (AD). We tested whether macrostructural differences in brain volume are related to the MMSE. METHODS: The MMSE was related to cortical thickness and the volume of 19 brain structures in 96 patients with mild to moderate AD. In addition, the patients were compared to 93 healthy elderly controls. RESULTS: The MMSE was related to the volume of the total brain, cerebral cortex, accumbens, cerebral white matter, inferior lateral ventricles and hippocampus. Positive correlations with cortical thickness were found for 41% of the brain surface, and 58% of this area was significantly thinner in AD. CONCLUSION: The MMSE is sensitive to macrostructural brain atrophy in AD, but also to morphometric variation not specifically related to AD.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/*pathology/*psychology;Atrophy;Brain/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Memory/physiology;Middle Aged;Nerve Net/pathology;*Neuropsychological Tests","Fjell, A. M.;Amlien, I. K.;Westlye, L. T.;Walhovd, K. B.",2009,,10.1159/000241878,0,
4374,No Evidence That Short-Term Cognitive or Physical Training Programs or Lifestyles Are Related to Changes in White Matter Integrity in Older Adults at Risk of Dementia,"Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer's disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n = 13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n = 14), or a control group (n = 20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer's disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (beta >/= 0.40, p </= 0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were related to FA scores at baseline (cognitive training skills and FA composite score, rs = 0.68, p = 0.05; functional physical fitness and fornix FA, r = 0.35, p = 0.03). Overall, we found no evidence of a link between short-term physical or cognitive activities and WMI changes, despite activity-related cognitive changes in older adults at risk of dementia. However, we found positive associations between the two targeted training outcomes and WMI, hinting at a potential of long-term activities to affect WMI.",cognitive lifestyle;cognitive training;dementia;memory complaints;older adults;physical lifestyle;physical training;white matter integrity,"Fissler, P.;Muller, H. P.;Kuster, O. C.;Laptinskaya, D.;Thurm, F.;Woll, A.;Elbert, T.;Kassubek, J.;von Arnim, C. A.;Kolassa, I. T.",2017,,,0,
4375,TCD-profiling using AVERAGE. A new technique to evaluate transcranial doppler ultrasound flow spectra of subjects with cerebral small vessel disease,"Background: There is an unmet need for screening methods to detect and quantify cerebral small vessel disease (SVD). Transcranial Doppler ultrasound (TCD) flow spectra of the larger intracranial arteries probably contain relevant information about the microcirculation. However, it has not yet been possible to exploit this information as a valuable biomarker. Methods: We developed a technique to generate normalized and averaged flow spectra during middle cerebral artery Doppler ultrasound examinations. Second, acceleration curves were calculated, and the absolute amount of the maximum positive and negative acceleration was calculated. Findings were termed 'TCD-profiling coefficient' (TPC). Validation study: we applied this noninvasive method to 5 young adults for reproducibility. Degenerative microangiopathy study: we also tested this new technique in 30 elderly subjects: 15 free of symptoms but with MRI-verified presence of cerebral SVD, and 15 healthy controls. SVD severity was graded according to a predefined score. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) study: TPC values of 10 CADASIL patients were compared with those of 10 healthy controls. Pulse wave analysis and local measurements of carotid stiffness were also performed. CADASIL patients were tested for cognitive impairment with the Montreal Cognitive Assessment scale. White matter and basal ganglia lesions in their cerebral MRI were evaluated according to the Wahlund score. Results: Validation study: the technique delivered reproducible results. Degenerative microangiopathy study: patients with SVD had significantly larger TPCs compared with controls (SVD: 2,132; IQR 1,960-2,343 %/s vs. controls: 1,935; IQR 1,782-2,050 %/s, p = 0.01). TPC values of subjects with SVD significantly correlated with SVD severity scores (R = 0.58, n = 15, p < 0.05). CADASIL study: TPC values of CADASIL patients were significantly higher than values of the controls (CADASIL: 2,504; IQR 2,308-2,930 %/s vs. controls 2,084; 1,839-2,241 %/s, p = 0.008), and also significantly higher than the TPC values of the patients with SVD from the degenerative microangiopathy study (p = 0.007). CADASIL patients had significantly worse cognitive test results than healthy controls. Conclusion: TCD-profiling detects impairment of the cerebral microcirculatory state. The suitability of the TCD-profiling for the evaluation of cerebral microangiopathy was confirmed.",adult;aged;arterial stiffness;artery compliance;article;basal ganglion;blood pressure;CADASIL;cerebrovascular disease;cognitive defect;controlled study;Doppler echography;Doppler flowmetry;female;heart cycle;human;imaging software;major clinical study;male;microangiopathy;middle cerebral artery;Montreal cognitive assessment;non invasive procedure;nuclear magnetic resonance imaging;priority journal;pulse wave;reproducibility;transcranial doppler;transducer;validation study;white matter;AVERAGE;HDI 5000;Logiq S6;Multidop T2;Multidop X4,"Fisse, A. L.;Pueschel, J.;Deppe, M.;Ringelstein, E. B.;Ritter, M. A.",2016,,,0,
4376,Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID),"This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.","Aged;Alzheimer Disease/*drug therapy/psychology;Brain Mapping/instrumentation;Cerebral Cortex/drug effects;Dementia, Multi-Infarct/*drug therapy/psychology;Double-Blind Method;Electroencephalography/drug effects/instrumentation;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Pyrithioxin/adverse effects/*therapeutic use;Signal Processing, Computer-Assisted/instrumentation;Single-Blind Method","Fischhof, P. K.;Saletu, B.;Ruther, E.;Litschauer, G.;Moslinger-Gehmayr, R.;Herrmann, W. M.",1992,,118898,0,
4377,Therapeutic efficacy of vincamine in dementia,"This trial was performed to investigate the therapeutic efficacy of vincamine in the treatment of primary degenerative and vascular dementia. 152 male and female patients aged between 50 and 85 years from two psychogeriatric centers and two nursing homes were initially included in the trial and screened for eligibility. 142 patients completed the trial. Clinical diagnosis was established according to DSM-III-R criteria. Allocation of the patients to the primary degenerative dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID) group was based on computed tomography scans, electroencephalographic findings and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30 mg vincamine or placebo was given twice daily. Confirmatory statistics included item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the nurse's rating of geriatric patients (Beurteilungsskala fur geriatrische Patienten; BGP) and the total score of the Short Cognitive Performance Test (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response were evaluated based on descriptive statistics. The therapeutic efficacy of vincamine was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all four target variables. The clinical relevance of the outcome was further underlined by the results of the responder analysis of the variables SCAG, BGP and SKT. Based on the results of this trial, it can be accepted that the therapeutic effect of vincamine is superior to placebo in patients with mild to moderate dementia of degenerative and vascular etiologies.","Aged;Aged, 80 and over;Alzheimer Disease/*drug therapy;Dementia/*drug therapy;Double-Blind Method;Female;Humans;Male;Middle Aged;Psychiatric Status Rating Scales;Vincamine/*therapeutic use","Fischhof, P. K.;Moslinger-Gehmayr, R.;Herrmann, W. M.;Friedmann, A.;Russmann, D. L.",1996,,,0,
4378,VITA study: white matter hyperintensities of vascular and degenerative origin in the elderly,"The etiology of white matter hyperintensities (WMH) seen on T2-weighted cranial magnetic resonance images is a matter of debate. We investigated deep and periventricular WMH in the brains of a community-based cohort of 532 subjects aged 75-76 years. The objective of this study was to determine whether WMH at age of 75 years were associated rather with vascular factors than with degenerative factors. Arterial hypertension treated with antihypertensive drugs favored WMH, and WMH were found more frequently in subjects with focal vascular lesions. Additionally, we found significant associations between both, deep white matter and periventricular hyperintensities, and focal atrophy of medial temporal lobe structures. The odds ratio for deep WMH in subjects with more severe medial temporal atrophy was 4.4 (95%-CI: 1.9-9.8) that for periventricular hyperintensities was 3.9 (95%-CI: 1.7-8.8). These findings might indicate that not only vascular factors alone but also degenerative factors favor the occurrence of WMH after the age of 75 years.","Age Factors;Aged;Alzheimer Disease/ pathology;Atrophy;Austria;Brain/ pathology;Cerebral Ventricles/pathology;Cohort Studies;Dementia, Multi-Infarct/pathology;Dementia, Vascular/ pathology;Female;Hippocampus/pathology;Humans;Hypertensive Encephalopathy/pathology;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Neurodegenerative Diseases/ pathology;Risk Factors;Temporal Lobe/pathology","Fischer, P.;Krampla, W.;Mostafaie, N.;Zehetmayer, S.;Rainer, M.;Jungwirth, S.;Huber, K.;Bauer, K.;Hruby, W.;Riederer, P.;Tragl, K. H.",2007,,,0,
4379,Altered whole-brain white matter networks in preclinical Alzheimer's disease,Abstract Surrogates of whole-brain white matter (WM) networks reconstructed using diffusion tensor imaging (DTI) are novel markers of structural brain connectivity. Global connectivity of networks has been found impaired in clinical Alzheimer's disease (AD) compared to cognitively healthy aging. We hypothesized that network alterations are detectable already in preclinical,,"Fischer, F. U.;Wolf, D.;Scheurich, A.;Fellgiebel, A.",2015,,,0,
4380,CADASIL: Angiopathy caused by NOTCH3 mutations,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common cause for inherited cases of stroke. The symptoms include migraine, recurrent ischemic events followed by episodes of lacunar stroke with onset in mid-adulthood. This results in neuropsychiatric disorders and dementia. The disease is caused by an angiopathy which affects mainly vascular smooth muscle cells of small and mid-sized arteries leading to degeneration and infiltration of the vascular wall with a consecutive narrowing of the lumen. CADASIL is caused by NOTCH3 mutations. This gene encodes a transmembrane receptor, which regulates proliferation and apoptosis in vascular smooth muscle cells. Magnetic resonance imaging, skin biopsy and mutation screening are sensitive diagnostic tools. There is no causative therapy up to now.",,"Fischer, A.",2006,December,,0,
4381,"Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure","Hypertension is a major risk factor for stroke and dementia and is associated with white matter hyperintensities (WMH) and reduced brain volumes. We measured the increase in WMH volume, and rate of cerebral atrophy over two years, in hypertensive subjects participating in the Study on COgnition and Prognosis in the Elderly (SCOPE), receiving candesartan or placebo, and normotensive controls. We recruited 163 subjects who had MRI (FLAIR and volumetric T1) at 2 and 4 years after baseline assessment. From these two scans, volumetric change in WMH (n = 133) and brain atrophy rates (n = 95) were determined. Total WMH fraction increased in both normotensive and treated hypertensive groups (p < 0.01) median change: 0.05% of brain volume [range: -0.45% to 1.51%]. Deep WMH increased in hypertensive (p = 0.001) but not the normotensive group. The number of subjects with an increase of total WMH in the 5(th) quintile differed between the treatment groups (chi square p = 0.006), being greatest in the placebo group (32%), then candesartan (20%) then normotensive (5%). Regression analysis found significant predictors of change in WMH to be blood pressure and initial deep WMH, but not treatment group. Increased atrophy rate was predicted by baseline systolic blood pressure (p = 0.02) but was not associated with measures of WMH. Similar to WMH, there was a trend with treatment, with atrophy in normotensive < Candesartan < Placebo (Spearman's rho = 0.23, p = 0.026). Hypertension in older people is associated with increased rates of progressive whole brain atrophy and an increase in WMH. These changes are independent. Successful hypertension treatment was associated with reduced risk of WMH progression and possibly brain atrophy.","0 (Antihypertensive Agents);Aged;Aged, 80 and over;Aging/pathology;Antihypertensive Agents/therapeutic use;Atrophy/etiology/ pathology/physiopathology;Blood Pressure/drug effects/ physiology;Brain/blood supply/ pathology/physiopathology;Cohort Studies;Dementia, Vascular/etiology/ pathology/physiopathology;Double-Blind Method;Female;Humans;Hypertension/ complications/drug therapy;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Placebo Effect;Predictive Value of Tests;Treatment Outcome","Firbank, M. J.;Wiseman, R. M.;Burton, E. J.;Saxby, B. K.;O'Brien, J. T.;Ford, G. A.",2007,Jun,,0,4382
4382,"Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure. Brain atrophy, WMH change and blood pressure","Hypertension is a major risk factor for stroke and dementia and is associated with white matter hyperintensities (WMH) and reduced brain volumes. We measured the increase in WMH volume, and rate of cerebral atrophy over two years, in hypertensive subjects participating in the Study on COgnition and Prognosis in the Elderly (SCOPE), receiving candesartan or placebo, and normotensive controls. We recruited 163 subjects who had MRI (FLAIR and volumetric T1) at 2 and 4 years after baseline assessment. From these two scans, volumetric change in WMH (n = 133) and brain atrophy rates (n = 95) were determined. Total WMH fraction increased in both normotensive and treated hypertensive groups (p < 0.01) median change: 0.05% of brain volume [range: -0.45% to 1.51%]. Deep WMH increased in hypertensive (p = 0.001) but not the normotensive group. The number of subjects with an increase of total WMH in the 5(th) quintile differed between the treatment groups (chi square p = 0.006), being greatest in the placebo group (32%), then candesartan (20%) then normotensive (5%). Regression analysis found significant predictors of change in WMH to be blood pressure and initial deep WMH, but not treatment group. Increased atrophy rate was predicted by baseline systolic blood pressure (p = 0.02) but was not associated with measures of WMH. Similar to WMH, there was a trend with treatment, with atrophy in normotensive < Candesartan < Placebo (Spearman's rho = 0.23, p = 0.026). Hypertension in older people is associated with increased rates of progressive whole brain atrophy and an increase in WMH. These changes are independent. Successful hypertension treatment was associated with reduced risk of WMH progression and possibly brain atrophy.","Aging [pathology];Antihypertensive Agents [therapeutic use];Atrophy [etiology] [pathology] [physiopathology];Blood Pressure [drug effects] [physiology];Brain [blood supply] [pathology] [physiopathology];Cohort Studies;Dementia, Vascular [etiology] [pathology] [physiopathology];Double-Blind Method;Hypertension [complications] [drug therapy];Magnetic Resonance Imaging;Nerve Fibers, Myelinated [pathology];Placebo Effect;Predictive Value of Tests;Treatment Outcome;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-dementia: sr-htn: sr-stroke","Firbank, M. J.;Wiseman, R. M.;Burton, E. J.;Saxby, B. K.;O'Brien, J. T.;Ford, G. A.",2007,,10.1007/s00415-006-0238-4,0,
4383,Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease,"OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.",,"Firbank, M. J.;Watson, R.;Mak, E.;Aribisala, B.;Barber, R.;Colloby, S. J.;He, J.;Blamire, A. M.;O'Brien, J. T.",2016,Mar,10.1016/j.parkreldis.2016.01.003,0,
4384,Homocysteine is associated with hippocampal and white matter atrophy in older subjects with mild hypertension,"Background: Plasma homocysteine has been associated with reduced brain volumes in cross-sectional studies. We aimed to investigate if homocysteine is associated with ongoing atrophy, and if so, if this is localized to gray or white matter. Methods: In a group of 80 hypertensive subjects aged 70-90 years (from the SCOPE study) MRI images were obtained at two time points two years apart. Rates of gray and white matter and hippocampal atrophy were determined by calculating the difference in segmentation probability maps using SPM5. Plasma homocysteine, folate, B12 and creatinine were measured at study end. Results: Homocysteine levels correlated with white matter atrophy rate (p = 0.006) hippocampal baseline volume (p = 0.011) and hippocampal atrophy rate (p = 0.004) but not global gray matter atrophy or baseline gray or white matter volumes. The correlations remained significant (p < 0.05) after controlling for subject age, blood pressure, folate levels and white matter lesion volume. Conclusion: In older hypertensives, plasma homocysteine levels are associated with increased rates of progressive white matter and hippocampal atrophy. Copyright © 2010 International Psychogeriatric Association.",,"Firbank, M. J.;Narayan, S. K.;Saxby, B. K.;Ford, G. A.;O'Brien, J. T.",2010,August,,0,
4385,Cerebral blood flow by arterial spin labeling in poststroke dementia,"OBJECTIVE: To investigate the relationship between cerebral blood flow and dementia in older stroke survivors and subjects with Alzheimer disease (AD). METHODS: This cohort study used arterial spin labeling MRI at 3 T to examine cerebral blood flow (CBF). We scanned 39 patients 6 years after stroke. They were older than 75 years at the time of stroke and free of dementia 3 months poststroke, with 8 subsequently developing dementia. We also scanned 17 subjects with AD and 29 healthy control subjects. We determined the perfusion in regions of interest (ROIs). Hippocampal volume was also measured using a previously validated automated procedure. RESULTS: The gray matter/white matter CBF ratio was reduced globally in the poststroke dementia (PSD) group (1.55 SD = 0.12) relative to control subjects (1.78 SD = 0.18; p = 0.03). The CBF ratio in a parietal ROI was reduced in the AD (1.34 SD = 0.31; p = 0.003), PSD (1.32 SD = 0.22; p = 0.041), and poststroke no-dementia (PSND) (1.44 SD = 0.34; p = 0.014) groups relative to that of control subjects (1.70 SD = 0.32). In subjects without stroke, the best predictor of dementia was hippocampus volume, whereas in the stroke group, it was the global CBF gray matter/white matter ratio. Hippocampus volume was not significantly different between the AD and PSD groups, and both had reduced hippocampi relative to those of control subjects and the PSND group. CONCLUSIONS: We found evidence for both vascular and AD pathology in PSD, suggesting that both the direct impact of the stroke and subsequent development of AD-type changes play a role in the etiology of PSD.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/physiopathology;Blood Circulation Time/methods;Brain/*blood supply;Cerebral Arteries/*physiopathology;Cerebrovascular Circulation/*physiology;Dementia/etiology/*pathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;*Spin Labels;Statistics, Nonparametric;Stroke/complications","Firbank, M. J.;He, J.;Blamire, A. M.;Singh, B.;Danson, P.;Kalaria, R. N.;O'Brien, J. T.",2011,Apr 26,10.1212/WNL.0b013e318217e76a,0,
4386,Medial temporal atrophy rather than white matter hyperintensities predict cognitive decline in stroke survivors,"Stroke is an important risk factor for dementia, but the exact mechanisms involved in cognitive decline remain unclear. In this study, we related baseline MRI brain measures with later cognitive decline. Seventy-nine stroke survivors aged 75+ years without dementia were recruited 3-month post-stroke. They underwent yearly neuropsychological assessments and had an MRI at baseline and 2 years. Medial temporal lobe atrophy (MTA) was scored and volume of white matter hyperintensities (WMH) was measured at baseline. The rate of ventricular enlargement was measured by comparing the baseline and repeat images. Linear regression indicated that memory loss was related to both baseline memory and MTA (p=0.001; standardized regression coefficient beta=-0.35) but not WMH volume. The only independent predictor of ventricular enlargement was MTA (p=0.003; beta=0.47). However, no baseline MRI variable differed between those who did (18%) and did not (82%) develop dementia. The association of MTA but not WMH with subsequent cognitive decline and increasing brain atrophy suggests a greater role for Alzheimer type than vascular pathology in delayed cognitive impairment after stroke.","Aged;Aged, 80 and over;Atrophy/pathology/psychology;Cognition Disorders/diagnosis/ pathology/psychology;Cohort Studies;Female;Follow-Up Studies;Humans;Male;Nerve Fibers, Myelinated/ pathology;Predictive Value of Tests;Stroke/diagnosis/ pathology/psychology;Survivors;Temporal Lobe/ pathology","Firbank, M. J.;Burton, E. J.;Barber, R.;Stephens, S.;Kenny, R. A.;Ballard, C.;Kalaria, R. N.;O'Brien, J. T.",2007,Nov,10.1016/j.neurobiolaging.2006.07.009,0,
4387,Diffusion tensor imaging in Alzheimer's disease and dementia with Lewy bodies,"White matter changes have been investigated in Alzheimer's disease (AD) in a number of studies using diffusion imaging. Fewer studies have investigated dementia with Lewy bodies (DLB). We used diffusion-weighted magnetic resonance imaging (MRI) and high-resolution (0.3 mm in-plane) coronal 3T MRI of the medial temporal lobe in 16 subjects with AD, 16 with DLB and 16 similarly aged healthy subjects. We found increased mean diffusivity in the temporal lobe of AD, and reduced fractional anisotropy (FA) in a small cluster in the right postcentral gyrus region in the DLB group. Mean FA in this cluster correlated with UPDRS (Unified Parkinson's Disease Rating Scale) motor score. We had previously reported reduced visibility in the AD group of a dark appearing layer of the hippocampus in the high-resolution images. In an SPM analysis on all subjects, there were significant clusters of reduced FA in the corpus callosum, fornix and stria terminalis that correlated with the visual rating of the hippocampus. These results suggest that changes to the hippocampus are associated with structural changes to the white matter fibres of the hippocampus output, and that changes in motor function are associated with changes in white matter underlying somatosensory cortex.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Analysis of Variance;Brain/ pathology;Brain Mapping;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted;Lewy Body Disease/ pathology;Male;Middle Aged","Firbank, M. J.;Blamire, A. M.;Teodorczuk, A.;Teper, E.;Mitra, D.;O'Brien, J. T.",2011,Nov 30,10.1016/j.pscychresns.2011.08.002,0,
4388,Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease,"Hippocampal atrophy and posterior cingulate hypometabolism are common features of both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). These regions show correlated activity at rest as part of the 'default network', and they are connected by the cingulum, a white matter (WM) tract. We hypothesised that hippocampal atrophy would be associated with disruption of the cingulum, as determined by diffusion tensor imaging. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with a T1 weighted 3D sequence and diffusion tensor FLAIR imaging. The T1 images were segmented into grey and white matter and spatially normalised using SPM. Hippocampal atrophy was estimated by calculating the mean grey matter (GM) volume from a region of interest in standard space and global atrophy from the total CSF segmentation. Fractional anisotropy (FA) maps were calculated and also spatially normalised. Using SPM, a multivariate correlation of FA against hippocampal GM, global atrophy and disease group was performed. We found a bilateral region adjacent to the posterior cingulate and encompassing a branch of the cingulum where global atrophy correlated with fractional anisotropy, after controlling for diagnosis and hippocampal GM. The results suggest that dementia disease progression as measured by global atrophy is associated with disruption of the white matter which connects posterior cingulate and lateral parietal regions. Hence, in addition to the hypometabolism in these regions in AD and DLB, there is also disruption to the white matter connecting them. Future studies are needed to determine whether the disruption precedes or is consequent on atrophy or hypometabolism.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Anisotropy;Atrophy;Diffusion Magnetic Resonance Imaging;Energy Metabolism/physiology;Female;Gyrus Cinguli/ pathology;Hippocampus/pathology;Humans;Image Enhancement;Image Processing, Computer-Assisted;Lewy Body Disease/ diagnosis/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Nerve Net/pathology;Neural Pathways/pathology;Parietal Lobe/pathology","Firbank, M. J.;Blamire, A. M.;Krishnan, M. S.;Teodorczuk, A.;English, P.;Gholkar, A.;Harrison, R.;O'Brien, J. T.",2007,May 15,10.1016/j.neuroimage.2007.02.027,0,
4389,Validation of a fully automated hippocampal segmentation method on patients with dementia,"We describe a fully automated method for hippocampal segmentation. The method uses SPM5 (http://www.fil.ion.ucl.ac.uk/spm/) software to segment the brain into grey/white matter, and spatially normalize the images to standard space. Grey matter pixels within a predefined hippocampal region in standard space are identified to segment the hippocampi. The method was validated on 36 subjects (9 each of Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and healthy controls). The mean absolute difference in volume compared with manual segmentation was 11% (SD 9%). Linear regression between manual and automated volume gave V(auto) = V(manual) x 0.83 + 401 ml. The method provides an acceptable automated alternative to manual segmentation which may be of value in large studies.","Aged;Aged, 80 and over;Alzheimer Disease/pathology/physiopathology;Automation/methods;Brain Mapping/ methods;Dementia/ pathology/physiopathology;Dementia, Vascular/pathology/physiopathology;Female;Hippocampus/ pathology/physiopathology;Humans;Image Processing, Computer-Assisted/ methods;Lewy Body Disease/pathology/physiopathology;Magnetic Resonance Imaging/ methods;Male;Predictive Value of Tests;Software;Software Validation","Firbank, M. J.;Barber, R.;Burton, E. J.;O'Brien, J. T.",2008,Dec,10.1002/hbm.20480,0,
4390,Neuroimaging predictors of death and dementia in a cohort of older stroke survivors,"BACKGROUND: Stroke is a risk factor for subsequent death and dementia. Being able to identify subjects at particular risk would be beneficial to inform treatment and patient management. METHODS SUBJECTS: aged over 75 years with incident stroke were recruited. Subjects had a cognitive assessment at 3 months post stroke to exclude dementia, and had an MRI scan (n=106) at that time. Subjects were then followed longitudinally for incident dementia and/or death. RESULTS: Independent neuroimaging predictors of survival to dementia were medial temporal atrophy (MTA; p=0.013) and the presence of thalamic infarcts (p=0.002). After inclusion of cognitive score in the model, the significance of MTA (p=0.049) and thalamic infarcts (p=0.04) was reduced, with survival being best predicted by baseline cognitive score (p=0.004). The only independent significant predictor of survival to death was MTA. Apart from thalamic infarcts, the NINDS/AIREN neuroimaging criteria did not independently predict survival to death or dementia. CONCLUSIONS: MTA was associated with shorter time to dementia, suggesting a role for Alzheimer pathology in the development of post stroke dementia.","Aged;Aged, 80 and over;Brain/pathology;Cohort Studies;Dementia/*etiology/pathology;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Multivariate Analysis;Neuroimaging/methods;Neuropsychological Tests;Proportional Hazards Models;Stroke/*complications/mortality/pathology;Survival Analysis;Survivors;Time Factors","Firbank, M. J.;Allan, L. M.;Burton, E. J.;Barber, R.;O'Brien, J. T.;Kalaria, R. N.",2012,Mar,10.1136/jnnp-2011-300873,0,
4391,Brain structural profile of multiple system atrophy patients with cognitive impairment,"Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of “subcortical cognitive impairment”.",adult;article;brain degeneration;brain size;clinical assessment;cognitive defect;controlled study;disease duration;dorsolateral prefrontal cortex;female;frontal gyrus;fusiform gyrus;human;image analysis;major clinical study;male;Mini Mental State Examination;multicenter study;neuroimaging;nuclear magnetic resonance imaging;onset age;parietal gyrus;priority journal;retrospective study;screening;Shy Drager syndrome;Unified Parkinson Disease Rating Scale;voxel based morphometry;white matter lesion,"Fiorenzato, E.;Weis, L.;Seppi, K.;Onofrj, M.;Cortelli, P.;Zanigni, S.;Tonon, C.;Kaufmann, H.;Shepherd, T. M.;Poewe, W.;Krismer, F.;Wenning, G.;Antonini, A.;Biundo, R.",2017,,10.1007/s00702-016-1636-0,0,
4392,[Parma stroke data bank: atherothrombotic and lacunar stroke] Parma stroke data bank: ictus aterotrombotico ed ictus lacunare,"In an epidemiological research about stroke, we studied 235 patients with atherothrombotic brain infarctions and 81 patients with lacunes. It was a longitudinal study concerning patients admitted to our Medical Division during the acute phase and followed up for one year after the onset. We report some anamnestic data, the frequency of positive brain CT scan, main risk factors, symptoms at the onset, severity degree of the stroke within the first 72 hours, complications during, and outcome after, the first four weeks, including personal performances and environmental fitness, mortality rate and frequency of relapses. We also report some of these data after one year from the acute episode.","Adult;Aged;Aged, 80 and over;Cerebral Infarction/ epidemiology;Databases, Factual;Dementia, Multi-Infarct/ epidemiology;Female;Follow-Up Studies;Humans;Intracranial Embolism and Thrombosis/ epidemiology;Italy;Longitudinal Studies;Male;Middle Aged;Risk Factors","Finzi, G.;Catamo, A.;Mombelloni, A.;Rossetti, A.;Silvestrini, C.;Tonelli, C.;Ponari, O.",1994,Nov,,0,
4393,[Parma stroke data bank: atherothrombotic and lacunar stroke],"In an epidemiological research about stroke, we studied 235 patients with atherothrombotic brain infarctions and 81 patients with lacunes. It was a longitudinal study concerning patients admitted to our Medical Division during the acute phase and followed up for one year after the onset. We report some anamnestic data, the frequency of positive brain CT scan, main risk factors, symptoms at the onset, severity degree of the stroke within the first 72 hours, complications during, and outcome after, the first four weeks, including personal performances and environmental fitness, mortality rate and frequency of relapses. We also report some of these data after one year from the acute episode.","Adult;Aged;Aged, 80 and over;Cerebral Infarction/*epidemiology;Databases, Factual;Dementia, Multi-Infarct/*epidemiology;Female;Follow-Up Studies;Humans;Intracranial Embolism and Thrombosis/*epidemiology;Italy;Longitudinal Studies;Male;Middle Aged;Risk Factors","Finzi, G.;Catamo, A.;Mombelloni, A.;Rossetti, A.;Silvestrini, C.;Tonelli, C.;Ponari, O.",1994,Nov,,0,
4394,Diffusion abnormality of corpus callosum in Alzheimer's disease,"This study investigated diffusion abnormalities in the parts of corpus callosum (CC) of patients with Alzheimer's disease (AD) using diffusion tensor magnetic resonance imaging (DT-MRI). Twenty-one patients with AD and 20 healthy volunteers participated in the study. MRI was performed with a 1.5 T system. Conventional MR images and diffusion tensor images were obtained for all participants. We divided the CC into three parts as rostrum, body and splenium. The apparent diffusion coefficiency (ADC) and fractional anisotropy (FA) were measured in all parts. FA values for the CC were lower in AD patients than the values of controls. In AD patients the lowest values were found in the rostrum of the CC and CC body FA values were also lower than the splenium, but the difference did not reach statistical significance. DT-MRI is a promising technique to investigate microstructural changes in white matter regions in AD. Early detection of the disease has been increasingly studied in AD. Further studies with larger populations are needed to confirm the role of diffusion tensor imaging in the evaluation of memory impairment.",,"Findikoglu, A.;Ercan, K.;Gunbey, H.",2011,May 15,,0,
4395,White matter dementia in CADASIL,"Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain' revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.",,"Filley, C. M.;Thompson, L. L.;Sze, C. I.;Simon, J. A.;Paskavitz, J. F.;Kleinschmidt-Demasters, B. K.",1999,1,,0,
4396,White matter dementia in chronic toluene abuse,"We studied 14 chronic toluene abusers with a comprehensive neuropsychological evaluation and cerebral magnetic resonance imaging (MRI). There were 10 men and 4 women, and the mean age was 29 years. Using a blinded global assessment of neuropsychological functioning, we found 3 patients to be normal, 3 in a borderline range, and 8 impaired. Independent analyses of white matter changes on MRI disclosed that the degree of white matter abnormality was strongly correlated (p less than 0.01) with neuropsychological impairment. Dementia in toluene abuse appears to be related to severity of cerebral white matter involvement.",Adult;Brain/ pathology;Chronic Disease;Dementia/ chemically induced/pathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Substance-Related Disorders/ complications;Toluene/ adverse effects,"Filley, C. M.;Heaton, R. K.;Rosenberg, N. L.",1990,Mar,,0,
4397,Neuropsychological performance and magnetic resonance imaging in Alzheimer's disease and normal aging,"A neuropsychological screening battery (NSB) and cerebral magnetic resonance imaging (MRI) scan were given to 49 older individuals, 18 with clinically diagnosed Alzheimers's disease (AD) and 31 age-, sex-, and education-matched normal controls. All subjects were given the Mini-Mental State Examination (MMSE) and had an assessment of cerebrovascular risk factors (CVRFs). Computerized measurements of supratentorial brain, ventricle, and extra-axial fluid volumes were made, and detailed analyses of white matter hyperintensities (WMHs) on T(2)-weighted images were carried out. The NSB was superior to the MMSE in identifying patients with AD, in whom significantly greater brain atrophy was seen. Atrophy was strongly correlated with neuropsychological performance in the combined groups, although not in either group alone. The WMHs were more apparent in the AD group, although they were common in normal subjects as well. The CVRFs were infrequent in both groups. These results suggest that the NSB is useful in the diagnosis of AD and that brain atrophy is reliably demonstrated by MRI. The WMHs are common in the elderly and may not impair cognition; factors other than ischemia may contribute to their origin.",,"Filley, C. M.;Davis, K. A.;Schmitz, S. P.;Stears, J. C.;Heaton, R. K.;Kelly, J.;Culig, K. M.;Scherzinger, A. L.",1989,1989,,0,
4398,Fragile X tremor ataxia syndrome and white matter dementia,"OBJECTIVE: Fragile X tremor ataxia syndrome (FXTAS) is an inherited neurodegenerative disease in which dementia is common and disabling. The pathogenesis of dementia in FXTAS is poorly understood, but the salience of executive dysfunction and slowed processing speed, the frequent presence of the middle cerebellar peduncle sign on magnetic resonance imaging (MRI), and striking neuropathological alterations of white matter all suggest that myelinated tracts are significantly involved. This paper considers the role of white matter disease in FXTAS dementia, particularly with regard to the concept of white matter dementia (WMD). METHOD: A focused review of FXTAS in relation to known white matter disorders is provided to propose that the concept of WMD may illuminate the basis of dementia in FXTAS. The putative pathogenetic contribution of white matter involvement in other neurodegenerative diseases is also considered. RESULTS: Considerable evidence supports the importance of white matter disease in the pathogenesis of dementia in FXTAS. Whereas, gray matter regions are also involved, white matter degeneration is prominent, even early in the disease, and correlates with executive dysfunction and slowed processing speed. Evidence for white matter involvement in other neurodegenerative diseases lends additional support to the relevance of white matter in FXTAS. CONCLUSION: The dementia of FXTAS is closely related to the profile of WMD, and white matter involvement is also supported by MRI and neuropathological observations. White matter pathology is also relevant to the pathogenesis of other neurodegenerative diseases. Further study of white matter promises to clarify the origin of dementia in FXTAS.",Fxtas;Mri;dementia;neuropsychology;white matter,"Filley, C. M.",2016,Aug,10.1080/13854046.2016.1165805,0,
4399,White matter dementia,"White matter dementia (WMD) is a syndrome introduced in 1988 to highlight the potential of cerebral white matter disorders to produce cognitive loss of sufficient severity to qualify as dementia. Neurologists have long understood that such a syndrome can occur, but the dominance of gray matter as the locus of higher function has strongly directed neurobehavioral inquiry to the cerebral cortex while white matter has received less attention. Contemporary neuroimaging has been crucial in enabling the recognition of white matter abnormalities in a host of disorders, and the correlation of these changes with cognitive performance. Comprising about half the brain, white matter is prominently or exclusively involved in well over 100 disorders, in each of which white matter dysfunction can potentially cause or contribute to dementia. Neuropsychological findings from ten categories of white matter disorder lead to a convergence of findings that document remarkable neurobehavioral commonality among the dementias produced. More recently, the syndrome of mild cognitive dysfunction (MCD) has been introduced to expand the concept of WMD by proposing a precursor syndrome related to early white matter neuropathology. WMD and MCD inform the understanding of how white matter contributes to normal and abnormal cognition, and the specific neuroanatomic focus of these syndromes may enhance the diagnosis and treatment of many disabling disorders that do not primarily implicate the cerebral cortex. Forming essential connections within widely distributed neural networks, white matter is critical for rapid and efficient information transfer that complements the information processing of gray matter. As neuroimaging continues to advance, further information on white matter structure can be expected, and behavioral neurology will play a central role in elucidating the functional significance of these emerging data. By emphasizing the contribution of myelinated systems to higher function, the study of white matter and cognition represents investigation of the basic neuroscience of human behavior.",,"Filley, C. M.",2012,Sep,10.1177/1756285612454323,0,
4400,Toxic leukoencephalopathy,"The white matter of the brain is vulnerable to a wide variety of toxins. Leukoencephalopathy is being increasingly recognized in a number of different patient populations. The detection of early and subtle toxin effects has been facilitated by the advent of magnetic resonance imaging, which offers better resolution of white matter than other neuroimaging methods. Neuropathologic features of leukoencephalopathy are also becoming more completely elucidated. Injury to white matter has been described from cranial irradiation and cancer chemotherapeutic drugs, and from a number of other therapeutic agents, drugs of abuse, and environmental toxins. Many patients have reversible leukoencephalopathy, whereas others experience a progressive and irreversible course. Leukoencephalopathy is associated with neurobehavioral manifestations that may be subtle or devastating, and the syndrome of white matter dementia may result. The pathogenesis of toxic leukoencephalopathy remains largely unknown, and treatment is limited in most cases to prevention by avoidance or minimization of the toxin exposure. However, the prognosis for this syndrome may be relatively favorable because of the frequent sparing of axons even when myelin is affected. Toxic leukoencephalopathy is an emerging clinical disorder that presents the opportunity for improving clinical outcomes in a number of patient groups and for achieving a deeper understanding of the role of white matter in cognitive and emotional function.",,"Filley, C. M.",1999,September/October,,0,
4401,Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE epsilon4 carriers,"PURPOSE: To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers. MATERIALS AND METHODS: A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter. RESULTS: We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. CONCLUSION: APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/*genetics/*pathology;Apolipoprotein E4/*genetics/metabolism;Atrophy/pathology;Cognition;Corpus Callosum/*pathology;Female;Genetic Predisposition to Disease/genetics;Heterozygote;Humans;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Neural Pathways/*pathology/physiopathology;Prefrontal Cortex/*pathology;Reference Values","Filippini, N.;Zarei, M.;Beckmann, C. F.;Galluzzi, S.;Borsci, G.;Testa, C.;Bonetti, M.;Beltramello, A.;Ghidoni, R.;Benussi, L.;Binetti, G.;Frisoni, G. B.",2009,May,10.1002/jmri.21757,0,
4402,Gray matter damage predicts the accumulation of disability 13 years later in MS,"Objectives: To assess the value of conventional and magnetization transfer (MT) MRI measures of white matter (WM) and gray matter (GM) damage, and their 12-month change, in predicting longterm disability and cognitive impairment in multiple sclerosis (MS). Methods: Conventional and MT MRI brain scans were obtained at baseline and at 12 months in 73 patients, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale score and the MS severity score (MSSS) for a median period of 13.3 years. At 13-year follow-up, a neuropsychological assessment was also performed when possible. T2-hyperintense and T1-hypointense lesion volumes, GM fraction (GMF), WM fraction, thalamic fraction, average lesion MT ratio (MTR), average GM MTR, average normal-appearing WM MTR, and thalamic MTR were measured. Random forest and multivariable analyses were performed to identify the predictors of neurologic deterioration and cognitive impairment at 13 years. Results: At 13-year follow-up, 66% of patients showed significant worsening of disability and 37% had worsened cognitively. The multivariable model, in which Expanded Disability Status Scale deterioration at final follow-up was the dependent variable, identified baseline GMF (odds ratio [OR] = 0.79, p = 0.01) as the only predictor of worsening of disability (C-index = 0.69). Baseline disease duration (OR = 1.50, p = 0.08) and average GM MTR (OR = 0.87, p = 0.03) were independent variables associated with cognitive deterioration (C-index 5 0.97). Baseline MSSS (β = 0.50, p < 0.0001) and baseline GMF (β = 20.32, p = 0.0005) predicted MSSS at follow-up (r2 = 0.45). Conclusions: GM damage is one of the key factors associated with long-term accumulation of disability and cognitive impairment in MS. © 2013 American Academy of Neurology.",adult;article;brain atrophy;brain damage;brain scintiscanning;central nervous system disease;cognitive defect;demyelinating disease;disability;disease duration;disease severity;Expanded Disability Status Scale;female;follow up;gray matter damage;human;immunosuppressive treatment;major clinical study;male;mental deterioration;multiple sclerosis;neuropsychological test;nuclear magnetic resonance imaging;priority journal;prospective study;random forest;relapse;treatment duration;white matter injury,"Filippi, M.;Preziosa, P.;Copetti, M.;Riccitelli, G.;Horsfield, M. A.;Martinelli, V.;Comi, G.;Rocca, M. A.",2013,,,0,
4403,Structural and functional network connectivity breakdown in Alzheimer's disease studied with magnetic resonance imaging techniques,"Patients with Alzheimer's disease (AD) experience a brain network breakdown, reflecting disconnection at both the structural and functional system level. Resting-state (RS) functional MRI (fMRI) studies demonstrated that the regional coherence of the fMRI signal is significantly altered in patients with AD and amnestic mild cognitive impairment. Diffusion tensor (DT) MRI has made it possible to track fiber bundle projections across the brain, revealing a substantially abnormal interplay of ""critical"" white matter tracts in these conditions. The observed agreement between the results of RS fMRI and DT MRI tractography studies in healthy individuals is encouraging and offers interesting hypotheses to be tested in patients with AD, aMCI, and other dementias in order to improve our understanding of their pathobiology in vivo. In this review, we describe the major findings obtained in AD using RS fMRI and DT MRI tractography, and discuss how the relationship between structure and function of the brain networks in AD may be better understood through the application of MR-based technology. This research endeavor holds a great promise in clarifying the mechanisms of cognitive decline in complex chronic neurodegenerative disorders. © 2011 IOS Press and the authors. All rights reserved.",,"Filippi, M.;Agosta, F.",2011,2011,,0,
4404,Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain,"BACKGROUND AND PURPOSE: HIV enters the CNS early in the course of infection and produces neuropsychiatric impairment throughout the course of illness, which preferentially affects the subcortical white matter. The development of a neuroimaging marker of HIV may allow for the earliest detection of cognitive impairment. The purpose of this study was to determine whether MR diffusion tensor imaging can detect white matter abnormalities in patients who have tested positive for HIV. METHODS: Ten patients with HIV (eight men and two women; mean age, 42 years) underwent MR imaging of the brain with MR diffusion tensor imaging, which included routine fluid-attenuated inversion recovery and fast spin-echo T2-weighted imaging. Diffusion constants and anisotropy indices were calculated from diffusion tensor maps. Peripheral viral load, Centers for Disease Control staging, and cluster of differentiation 4 levels were determined. RESULTS: All patients had normal results of MR imaging of the brain, except for mild atrophy. Four of 10 patients had undetectable viral loads. These patients were receiving highly active antiretroviral therapy. The diffusion constant and anisotropy were normal. Four of 10 patients had viral loads between 10,000 and 200,000. Diffusion anisotropy in the splenium and genu was significantly decreased (P < .02). The diffusion constant of the subcortical white matter was elevated in the frontal and parietooccipital lobes (11%). Two of 10 patients had viral loads >400,000. Anisotropy of the splenium was half normal (P < .0004) and of the genu was decreased 25% (P < .002). The average diffusion constant was diffusely elevated in the subcortical white matter. CONCLUSION: Calculating the diffusion constant and anisotropy in the subcortical white matter and corpus callosum in patients with HIV detected abnormalities despite normal-appearing white matter on MR images and nonfocal neurologic examinations. Patients with the highest diffusion constant elevations and largest anisotropy decreases had the most advanced HIV disease. Patients with the lowest viral load levels, who had normal anisotropy and diffusion constants, were receiving highly active antiretroviral therapy.",,"Filippi, C. G.;Uluǧ, A. M.;Ryan, E.;Ferrando, S. J.;Van Gorp, W.",2001,2001,,0,
4405,Regression of HIV encephalopathy and basal ganglia signal intensity abnormality at MR imaging in patients with AIDS after the initiation of protease inhibitor therapy,"PURPOSE: To determine whether protease inhibitors cause regression of periventricular white matter signal intensity abnormalities in patients with human immunodeficiency virus (HIV) encephalopathy and whether the changes on magnetic resonance (MR) images correlate with cognitive improvement. MATERIALS AND METHODS: MR images were retrospectively and prospectively analyzed in 16 adult patients with HIV encephalopathy. White matter and basal ganglia signal intensity abnormalities on initial long repetition time (TR) images were compared with those on subsequent long TR images in patients who received and in patients who did not receive protease inhibitors. Clinical correlation was obtained. RESULTS: Of the nine patients receiving protease inhibitors, four showed nearly complete regression, four showed interval stability, and one showed slight progression. Thus, eight patients (89%) demonstrated either stability or improvement in white matter disease, which correlated with cognitive improvement. Of the seven patients not receiving protease inhibitors, six (86%) showed marked progression with a decline in cognitive function and one had no interval change. The difference between the two groups was statistically significant. Of the two patients receiving protease inhibitors who initially had basal ganglia signal intensity abnormalities, one demonstrated resolution and one nearly complete resolution subsequently. CONCLUSION: Although the patient population is small, protease inhibitors may cause regression of periventricular white matter and basal ganglia signal intensity abnormalities in HIV encephalopathy and may have a role in treatment.",AIDS Dementia Complex/ drug therapy/ pathology/psychology;Adult;Basal Ganglia/ pathology;Brain/ pathology;Case-Control Studies;Cognition;Contrast Media;Disease Progression;Female;Gadolinium DTPA;HIV Protease Inhibitors/ therapeutic use;Humans;Magnetic Resonance Imaging;Male;Prospective Studies;Retrospective Studies,"Filippi, C. G.;Sze, G.;Farber, S. J.;Shahmanesh, M.;Selwyn, P. A.",1998,Feb,10.1148/radiology.206.2.9457204,0,
4406,Patterns of progressive atrophy vary with age in Alzheimer's disease patients,"Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices.",Aging;Alzheimer's disease;Atrophy;Early-onset Alzheimer's disease;Hippocampus;Late-onset;Mild cognitive impairment (MCI),"Fiford, C. M.;Ridgway, G. R.;Cash, D. M.;Modat, M.;Nicholas, J.;Manning, E. N.;Malone, I. B.;Biessels, G. J.;Ourselin, S.;Carmichael, O. T.;Cardoso, M. J.;Barnes, J.;Alzheimer's Disease Neuroimaging, Initiative",2018,Mar,,0,
4407,White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy,"This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Abeta42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Abeta42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. (c) 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.",Alzheimer's disease;hippocampus;mild cognitive impairment;vascular disease;white matter disease;white matter hyperintensity (WMH),"Fiford, C. M.;Manning, E. N.;Bartlett, J. W.;Cash, D. M.;Malone, I. B.;Ridgway, G. R.;Lehmann, M.;Leung, K. K.;Sudre, C. H.;Ourselin, S.;Biessels, G. J.;Carmichael, O. T.;Fox, N. C.;Cardoso, M. J.;Barnes, J.;Alzheimer's Disease Neuroimaging, Initiative",2017,Mar,,0,
4408,Impact of baseline adjustment for vascular risk factors on sample size for atrophy outcomes in Alzheimer's disease clinical trials,"Background: Whole-brain and hippocampal atrophy rate measures are used as outcomes measures in trials of putative therapies for Alzheimer's disease (AD). Since atrophy rates may be influenced by vascular risk factors or vascular brain injury, we investigated whether baseline adjustment for these characteristics may also reduce sample size estimates. Methods: Participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 study were included where they had useable 1.5T MRI imaging at baseline and 1 year follow-up. Boundary shift integral (BSI) was used to assess MRI whole-brain and hippocampal atrophy rates. Sample sizes per arm were estimated for a placebo controlled clinical trial in AD or MCI to have 80% power to detect a 25% reduction in atrophy rate and for 25% reduction relative to atrophy rates in controls. Sample sizes were calculated with adjustment for baseline age, diastolic and systolic blood pressure, fasting glucose, serum cholesterol, body mass index (BMI), smoking status, hypertension, diabetes, hyperlipidaemia, central and coronary heart disease, MRI infarcts, stroke-related events, and white matter hyperintensities. Results: Participants included 177 controls, 297 participants with MCI and 122 participants with AD at baseline. The mean whole-brain atrophy rates were: controls 5.9 ml/yr (SD 5.9); MCI 10.9 (8.3); AD 14.9 (7.7). Sample sizes per arm for a 25% reduction in whole-brain atrophy rate were 719 MCI and 186 AD.With adjustment for all vascular risk factors and vascular brain injury variables sample size were reduced by 3% in MCI and 10% in AD (Table 1). Hippocampal atrophy rates were: controls 0.06 ml/yr (SD 0.09); MCI 0.14 (0.12); AD 0.20 (0.12). Sample sizes per arm for 25% reduction in hippocampal atrophy were 544 MCI and 179 AD. Adjustment for all vascular risk factors reduced sample size estimates by 2.6% in MCI but there was no reduction in AD (Table 1). Conclusions: Adjustment for 14 vascular risk factors provided a modest reduction in sample size estimates of up to 10%. AD treatment trials which exclude patients with overt cerebrovascular disease, much like ADNI1, may still benefit from adjustment of whole-brain atrophy rate outcome measures by vascular risk factors and event.",atrophy;risk factor;sample size;clinical trial (topic);Alzheimer disease;human;brain atrophy;arm;brain injury;brain;controlled clinical trial (topic);nuclear magnetic resonance imaging;systolic blood pressure;patient;white matter;cerebrovascular disease;diet restriction;cerebrovascular accident;infarction;controlled clinical trial;ischemic heart disease;hyperlipidemia;follow up;diabetes mellitus;hypertension;smoking;body mass;cholesterol blood level;imaging;neuroimaging;therapy;placebo;glucose,"Fiford, C.;Frost, C.;Manning, E. N.;Nicholas, J.;Barnes, J.;Leung, K. K.;Carmichael, O. T.;Meade, T.",2014,,,0,
4409,Novel white matter tract integrity metrics sensitive to Alzheimer disease progression,"BACKGROUND AND PURPOSE: Along with cortical abnormalities, white matter microstructural changes such as axonal loss and myelin breakdown are implicated in the pathogenesis of Alzheimer disease. Recently, a white matter model was introduced that relates non-Gaussian diffusional kurtosis imaging metrics to characteristics of white matter tract integrity, including the axonal water fraction, the intra-axonal diffusivity, and the extra-axonal axial and radial diffusivities. MATERIALS AND METHODS: This study reports these white matter tract integrity metrics in subjects with amnestic mild cognitive impairment (n = 12), Alzheimer disease (n = 14), and age-matched healthy controls (n = 15) in an effort to investigate their sensitivity, diagnostic accuracy, and associations with white matter changes through the course of Alzheimer disease. RESULTS: With tract-based spatial statistics and region-of-interest analyses, increased diffusivity in the extra-axonal space (extra-axonal axial and radial diffusivities) in several white matter tracts sensitively and accurately discriminated healthy controls from those with amnestic mild cognitive impairment (area under the receiver operating characteristic curve = 0.82-0.95), while widespread decreased axonal water fraction discriminated amnestic mild cognitive impairment from Alzheimer disease (area under the receiver operating characteristic curve = 0.84). Additionally, these white matter tract integrity metrics in the body of the corpus callosum were strongly correlated with processing speed in amnestic mild cognitive impairment (r = |0.80-0.82|, P < .001). CONCLUSIONS: These findings have implications for the course and spatial progression of white matter degeneration in Alzheimer disease, suggest the mechanisms by which these changes occur, and demonstrate the viability of these white matter tract integrity metrics as potential neuroimaging biomarkers of the earliest stages of Alzheimer disease and disease progression.","Aged;Algorithms;Alzheimer Disease/complications/ pathology;Diffusion Tensor Imaging/ methods;Disease Progression;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Male;Mild Cognitive Impairment/complications/ pathology;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity;Severity of Illness Index","Fieremans, E.;Benitez, A.;Jensen, J. H.;Falangola, M. F.;Tabesh, A.;Deardorff, R. L.;Spampinato, M. V.;Babb, J. S.;Novikov, D. S.;Ferris, S. H.;Helpern, J. A.",2013,Nov-Dec,10.3174/ajnr.A3553,0,
4410,Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936,"It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.",Aged;Brain/ diagnostic imaging;Cerebral Small Vessel Diseases/ diagnostic imaging/etiology/psychology;Cognition/ physiology;Cohort Studies;Cost of Illness;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Risk Factors;Scotland;White Matter/ diagnostic imaging;Mri;aging;cerebral small vessel disease;stroke,"Field, T. S.;Doubal, F. N.;Johnson, W.;Backhouse, E.;McHutchison, C.;Cox, S.;Corley, J.;Pattie, A.;Gow, A. J.;Shenkin, S.;Cvoro, V.;Morris, Z.;Staals, J.;Bastin, M.;Deary, I. J.;Wardlaw, J. M.",2016,Sep 19,,0,4411
4411,Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936,"It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study.",Mri;aging;cerebral small vessel disease;risk factors;stroke,"Field, T. S.;Doubal, F. N.;Johnson, W.;Backhouse, E.;McHutchison, C.;Cox, S.;Corley, J.;Pattie, A.;Gow, A. J.;Shenkin, S.;Cvoro, V.;Morris, Z.;Staals, J.;Bastin, M.;Deary, I. J.;Wardlaw, J. M.",2016,Sep 19,10.18632/aging.101043,0,
4412,Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular Cognitive Impairment,"BACKGROUND: Cerebral microinfarcts (CMIs) are small ischemic lesions that are a common neuropathological finding in patients with stroke or dementia. CMIs in the cortex can now be detected in vivo on 3 Tesla MRI. OBJECTIVE: To determine the occurrence of CMIs and associated clinical features in patients with possible vascular cognitive impairment (VCI). METHOD: 182 memory-clinic patients (mean age 71.4+/-10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI) underwent a standardized work-up including 3 Tesla MRI and cognitive assessment. A control group consisted of 70 cognitively normal subjects (mean age 70.6+/-4.7, 60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury were rated according to established criteria. RESULT: Occurrence of CMIs was higher (20%) in patients compared to controls (10%). Among patients, the presence of CMIs was associated with male sex, history of stroke, infarcts, and white matter hyperintensities. CMI presence was also associated with a diagnosis of vascular dementia and reduced performance in multiple cognitive domains. CONCLUSION: CMIs on 3 Tesla MRI are common in patients with possible VCI and co-occur with imaging markers of small and large vessel disease, likely reflecting a heterogeneous etiology. CMIs are associated with worse cognitive performance, independent of other markers of vascular brain injury.",Cerebral small vessel disease;cerebrovascular disease;dementia;infarct;magnetic resonance imaging;neuropsychological test,"Ferro, D. A.;van Veluw, S. J.;Koek, H. L.;Exalto, L. G.;Biessels, G. J.;Utrecht Vascular Cognitive Impairment study, group",2017,,,0,
4413,"Progression from mild cognitive impairment to Alzheimer's disease: Effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment","OBJECTIVE: Evaluate the effect of sex and butyrylcholinesterase (BuChE) genotype on the incidence of Alzheimer's disease (AD), cognitive and functional decline, brain volume changes, and response to rivastigmine treatment in individuals with mild cognitive impairment (MCI). METHODS: This retrospective exploratory analysis from a 3-4 year, randomized, placebo-controlled study of rivastigmine in MCI patients included participants who consented to pharmacogenetic testing. RESULTS: Of a total of 1018 patients, 490 [253 (52%) female] were successfully genotyped for BuChE. In patients receiving placebo, the BuChE wt/wt genotype was associated with a statistically significant higher incidence of progression to AD and functional decline in women, compared with men with the BuChE wt/wt genotype. In patients with a BuChE-K allele receiving placebo, incidence of progression to AD and rate of functional decline were not significantly different by sex; however, cognitive decline was significantly faster in men. Statistically significant benefits of rivastigmine treatment on incident AD, functional decline, ventricular volume expansion, whole-brain atrophy, and white matter loss were evident in female BuChE wt/wt. CONCLUSION: Sex and BuChE genotype seem to differentially influence the type of decline in MCI patients, with more rapid progression of cognitive decline in male BuChE-K, and more incident AD and functional decline in female BuChE wt/wt. Cognitive decline in male BuChE-K and functional decline and incident AD in female BuChE wt/wt were significantly attenuated by rivastigmine. Rivastigmine treatment also significantly reduced ventricular expansion, whole-brain atrophy rate, and white matter loss in female BuChE wt/wt, suggesting a possible disease-modifying effect. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.",butyrylcholinesterase E;cholinesterase;esterase;placebo;rivastigmine;unclassified drug;aged;Alzheimer disease;article;brain atrophy;brain size;brain ventricle;clinical evaluation;clinical trial;cognitive defect;controlled clinical trial;controlled study;disease course;disease severity;double blind procedure;drug efficacy;enzyme activity;female;gene frequency;genotype;human;incidence;major clinical study;male;mental deterioration;multicenter study;nuclear magnetic resonance imaging;pharmacogenetics;priority journal;randomized controlled trial;retrospective study;sex difference;treatment duration;treatment response;white matter;wild type,"Ferris, S.;Nordberg, A.;Soininen, H.;Darreh-Shori, T.;Lane, R.",2009,,,0,
4414,Ubiquitin-negative mini-pick-like bodies in the dentate gyrus in p3011 tauopathy,"Neuropathological and biochemical findings are reported in a patient who had suffered from frontotemporal dementia associated with a P310L mutation in the tau gene and included in the H1 haplotype. Tau accumulation, as revealed with phospho-specific anti-tau antibodies Thr181, Ser199, Ser202, Ser214, Ser262, Ser396, Ser422 and AT8 (Ser202 and Thr205), was found in neurons with pre-tangles, and astrocytes and oligodendrocytes through the brain. The most characteristic feature was tau immunoreactivity decorating the perinuclear region and small cytoplasmic aggregates designed as mini-Pick-like bodies, mainly in the dentate gyrus. Inclusions were not stained with anti-ubiquitin antibodies and did not recruit tubulins. Tau accumulation in individual cells was associated with increased expression of kinases linked with tau phosphorylation, mainly active (phosphorylated) stress kinases SAPK/JNK and p38 (SAPK/JNK-P and p38-P). Phosphorylated GSK-3β at Ser9 (GSK-3β-P), that inactivates the kinase, was particularly abundant in mini-Pick-like bodies, thus suggesting alternative roles of GSK-3 probably involved in cell survival. Western blots of sarkosyl-insoluble fractions revealed a double band pattern of phospho-tau of 68/66 kDa and 64 kDa in the hippocampus and white matter in the P310L mutation. Sarkosyl-insoluble fractions of the hippocampus were enriched in p38-P and GSK-3β-P in Alzheimer's disease (AD) cases, processed in parallel for comparative purposes, but not in the P310L mutation. In addition, no bands of high molecular weight were found in P310L in contrast with AD in these fractions. These findings indicate that the major sites of tau phosphorylation, and the expression of kinases involved in tau phosphorylation are active in P310L mutation as in AD and other tauopathies. Yet the P310L mutation has particular phospho-tau inclusions that are not tag with ubiquitin and appear to be rather soluble when compared with AD.",tau protein;ubiquitin;adult;Alzheimer disease;article;brain atrophy;case report;degenerative disease;dementia;dentate gyrus;frontotemporal dementia;gene mutation;human;human tissue;immunohistochemistry;male;neurologic disease;neuropathology;nuclear magnetic resonance imaging;priority journal;tauopathy,"Ferrer, I.;Hernández, I.;Puig, B.;Rey, M. J.;Ezquerra, M.;Tolosa, E.;Boada, M.",2003,,,0,
4415,"Arteriolosclerotic leucoencephalopathy in the elderly and its relation to white matter lesions in Binswanger's disease, multi-infarct encephalopathy and Alzheimer's disease","Arteriolosclerotic leucoencephalopathy in the elderly (ALE) is characterized by white matter lesions associated with atherosclerosis and arteriolosclerosis. Mild lesions are focal and probably represent early status cribosus or incomplete lacunar infarcts. Moderate and severe lesions are diffuse areas of demyelination in the centrum semiovale in which lacunar infarcts are seldom observed. The incidence of ALE in a consecutive necropsy series of 50 cases (mean age 62.6 +/- 13.1 years) was 52%, it was rare in the fourth and fifth decades but increased thereafter to reach a prevalence of 100% at the age of 80 years. Mild lesions occurred in 19 patients and lesions were moderate or severe in 7 (14%). The mean age was higher in this group (74.7 +/- 7.6 years) than in patients with white matter changes as a whole. Dementia occurred only in 3 patients with moderate or severe ALE. These data suggest that (a) ALE is common in old age and is probably the cause of leuko-araiosis in most CT scans in the elderly; (b) ALE may be asymptomatic; (c) the severity of white matter changes may be not related to the severity of neurological deficits; and (d) multiple lacunar infarcts or associated degenerative diseases (i.e., Alzheimer's disease) may be the main cause of dementia in patients with ALE. White matter lesions in ALE, Binswanger's disease, transition areas in multi-infarct encephalopathy (MIE) and Alzheimer's disease (AD) are similar in morphology and are probably the result of a subacute hypoperfusion/hypoxic process. Increased arterial blood pressure is a frequent risk factor in ALE, Binswanger's disease and MIE, whereas congophilic angiopathy of the meningeal and cortical vessels, in addition to mild or moderate arteriolar hyalinosis in the white matter, may play a role in the pathogenesis of incomplete infarctation of the white matter in patients with AD.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Arterioles/pathology;Arteriosclerosis/complications/*pathology;Brain/*pathology;Brain Diseases/*complications;Cerebral Infarction/complications/*pathology;Dementia/*pathology;Female;Humans;Male;Middle Aged","Ferrer, I.;Bella, R.;Serrano, M. T.;Marti, E.;Guionnet, N.",1990,Aug,,0,
4416,"Coexistence of mixed phenotype Creutzfeldt-Jakob disease, Lewy body disease and argyrophilic grain disease plus histological features of possible Alzheimer's disease: A multi-protein disorder in an autopsy case","We report hereby an autopsy case of sporadic mixed phenotype CJD without hereditary burden and a long-term clinical course. An 80-year old man was diagnosed with mild cognitive impairment 27 months before death, caused by bronchopneumonia and severe respiratory impairment. During this time, the patient developed gradual mental deterioration, some sleeping problems and myoclonus. Other clinical manifestations were progressive gait problems, language deterioration, presence of primitive reflexes and irritability. In keeping with those symptoms, a rapidly evolving dementia was clinically suspected. Cerebrospinal fluid test for 14-3-3 protein was negative. However, an abnormal EEG and MRI at end-stage of disease were finally consistent with CJD. Post-mortem examination revealed a massive cortical neuronal loss with associated reactive astrocytosis, also evident in the white matter. Diffuse spongiform changes involving some basal ganglia, especially medial thalamus, some troncoencephalic nuclei, mainly inferior olivary nucleus and the molecular layer of the cerebellum were seen. Immunorreactive deposits for anti-prion protein antibody were present at different areas of the CNS. Additionally, Lewy bodies were observed at the brainstem and amygdala. Furthermore, argirophilic grains together with oligodendroglial coiled bodies and pre-tangle inclusions in the neurons from the limbic system containing hyperphosphorylated 4R tau were noted. To the best of our knowledge, this is the first case of CJD combined with Lewy body disease and argirophilic grain disease. Furthermore, we believe this case is an extremely rare combination of MM2-cortical-type and MM2-thalamic-type sporadic CJD (sCJD), which explains the broad spectrum of MM2-type sCJD findings and symptoms. Moreover, histological features of possible Alzheimer's disease were also reported.",alpha synuclein;amyloid beta protein;at8 antibody;cholinesterase inhibitor;congo red;monoclonal antibody;prion protein antibody;tau protein;unclassified drug;aged;Alzheimer disease;amnesia;amygdaloid nucleus;aphasia;argyrophilic grain disease;article;astrocyte;astrocytosis;autopsy;basal ganglion;birefringence;brain atrophy;brain stem;brain weight;bronchopneumonia;cerebellum;coiled body;Creutzfeldt Jakob disease;dementia;diffuse Lewy body disease;electroencephalogram;electroencephalography;fluency disorder;genetic analysis;hippocampal CA1 region;hippocampal CA2 region;hippocampal CA3 region;histology;human;human tissue;hypersomnia;immunohistochemistry;immunoreactivity;inferior olive;irritability;limbic system;locus ceruleus;male;mental deterioration;mild cognitive impairment;Mini Mental State Examination;myoclonus;neuropil thread;nuclear magnetic resonance imaging;occipital lobe;open reading frame;parkinsonian gait;periodic synchronous discharge;phenotype;priority journal;protein phosphorylation;reflex;respiratory tract disease;senile plaque;substantia nigra;temporal cortex;thalamus;tremor;unsteady gait;very elderly;Western blotting;white matter,"Fernández-Vega, I.;Ruiz-Ojeda, J.;Juste, R. A.;Geijo, M.;Zarranz, J. J.;Sánchez Menoyo, J. L.;Vicente-Etxenausia, I.;Mediavilla-García, J.;Guerra-Merino, I.",2015,,,0,4417
4417,"Coexistence of mixed phenotype Creutzfeldt-Jakob disease, Lewy body disease and argyrophilic grain disease plus histological features of possible Alzheimer's disease: A multi-protein disorder in an autopsy case","We report hereby an autopsy case of sporadic mixed phenotype CJD without hereditary burden and a long-term clinical course. An 80-year old man was diagnosed with mild cognitive impairment 27 months before death, caused by bronchopneumonia and severe respiratory impairment. During this time, the patient developed gradual mental deterioration, some sleeping problems and myoclonus. Other clinical manifestations were progressive gait problems, language deterioration, presence of primitive reflexes and irritability. In keeping with those symptoms, a rapidly evolving dementia was clinically suspected. Cerebrospinal fluid test for 14-3-3 protein was negative. However, an abnormal EEG and MRI at end-stage of disease were finally consistent with CJD. Post-mortem examination revealed a massive cortical neuronal loss with associated reactive astrocytosis, also evident in the white matter. Diffuse spongiform changes involving some basal ganglia, especially medial thalamus, some troncoencephalic nuclei, mainly inferior olivary nucleus and the molecular layer of the cerebellum were seen. Immunorreactive deposits for anti-prion protein antibody were present at different areas of the CNS. Additionally, Lewy bodies were observed at the brainstem and amygdala. Furthermore, argirophilic grains together with oligodendroglial coiled bodies and pre-tangle inclusions in the neurons from the limbic system containing hyperphosphorylated 4R tau were noted. To the best of our knowledge, this is the first case of CJD combined with Lewy body disease and argirophilic grain disease. Furthermore, we believe this case is an extremely rare combination of MM2-cortical-type and MM2-thalamic-type sporadic CJD (sCJD), which explains the broad spectrum of MM2-type sCJD findings and symptoms. Moreover, histological features of possible Alzheimer's disease were also reported. © 2014 Japanese Society of Neuropathology.",protein;protein 14 3 3;molecular layer;prion protein antibody;Creutzfeldt Jakob disease;diffuse Lewy body disease;grain;phenotype;nerve degeneration;immunohistochemistry;autopsy;diseases;Alzheimer disease;human;sporadic Creutzfeldt Jakob disease;mental deterioration;patient;bronchopneumonia;basal ganglion;sleep;death;cerebrospinal fluid;dementia;mild cognitive impairment;reflex;deterioration;irritability;language;astrocytosis;white matter;thalamus;inferior olivary nucleus;male;cerebellum;Lewy body;brain stem;amygdala;Japanese (people);gait;disease course;myoclonus;limbic system;nerve cell;coiled body;society;neuropathology;central nervous system;nuclear magnetic resonance imaging;electroencephalogram,"Fernández-Vega, I.;Ruiz-Ojeda, J.;Juste, R. A.;Geijo, M.;Zarranz, J. J.;Sánchez Menoyo, J. L.;Vicente-Etxenausia, I.;Mediavilla-García, J.;Guerra-Merino, I.",2014,,10.1111/neup.12150,0,
4418,Is there a specific pattern of attention deficit in mild cognitive impairment with subcortical vascular features? Evidence from the Attention Network Test,"BACKGROUND: Mild cognitive impairment (MCI) is an intermediate state between normal aging and early dementia. Some MCI patients show white matter hyperintensities in magnetic resonance imaging, revealing subcortical vascular damage (SVD). This study aimed to evaluate potential attention deficits not previously described in these patients. Specifically, we evaluated attention network functioning in MCI on the basis of Posner's cognitive neuroscience model, which considers attention as a set of networks: alerting, orienting and executive control. METHODS: Three groups of participants were tested: 19 MCI patients with SVD (svMCI), 15 MCI patients free from SVD (nvMCI) and 19 healthy controls (HC). We used a task in which the three attention networks and their interactions can be assessed simultaneously, the Attention Network Test (ANT). RESULTS: The svMCI group showed smaller orienting effect compared with the nvMCI and HC groups. In contrast to the HC and nvMCI groups, svMCI patients did not show improvement in the executive network from the valid visual cue. CONCLUSIONS: svMCI patients show a deficit in orienting attention networks. This deficit could be related to an effect of SVD on the cholinergic system because acetylcholine is implicated in the modulation of covert orienting responses of attention.","Acetylcholine/physiology;Aged;Aged, 80 and over;Atrophy;Attention/physiology;Attention Deficit Disorder with Hyperactivity/ pathology/ physiopathology;Cognition Disorders/ pathology/ physiopathology;Dementia, Vascular/ pathology/ physiopathology;Executive Function/physiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Severity of Illness Index","Fernandez, P. J.;Campoy, G.;Garcia Santos, J. M.;Antequera, M. M.;Garcia-Sevilla, J.;Castillo, A.;Antunez, C.;Fuentes, L. J.",2011,,10.1159/000327165,0,
4419,Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations,"The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804. A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804. A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples. © 2014 Elsevier Ireland Ltd.",,"Fernandes, C. P. D.;Westlye, L. T.;Giddaluru, S.;Christoforou, A.;Kauppi, K.;Adolfsson, R.;Nilsson, L. G.;Nyberg, L.;Lundervold, A. J.;Reinvang, I.;Steen, V. M.;Le Hellard, S.;Espeseth, T.",2014,30,,0,
4420,Conceptual elaboration versus direct lexical access in WAIS-similarities: differential effects of white-matter lesions and gray matter volumes,"Wechsler Adult Intelligence Scale (WAIS) subscale Similarities have been classified as a test of either verbal comprehension or of inductive reasoning. The reason may be that items divide into two categories. We tested the hypothesis of heterogeneity of items in WAIS-Similarities. Consecutive patients at a memory clinic and healthy controls participated in the study. White-matter hyperintensities (WMHs) and normalized temporal lobe volumes were measured based on Magnetic resonance Imaging (MRI), and tests of verbal memory and attention were used in addition to WAIS-Similarities to collect behavioural data. Factor analysis supported the hypothesis that two factors are involved in the performance of WAIS-similarities: (1) semiautomatic lexical access and (2) conceptual elaboration. These factors were highly correlated but provided discriminative diagnostic information: In logistic regression analyses, scores of the lexical access factor and of the conceptual elaboration factor discriminated patients with mild cognitive impairment from Alzheimer's disease patients and from healthy controls, respectively. High scores of WMH, indicating periventricular white-matter lesions, predicted factor scores of direct lexical access but not those of conceptual elaboration, which were predicted only by medial and lateral temporal lobe volumes.",WAIS-similarities;conceptual elaboration;gray matter volumes;lexical access;white-matter lesions,"Fernaeus, S. E.;Hellstrom, A.",2017,Sep 18,,0,
4421,White matter lesions impair initiation of FAS flow,"Word fluency performance is known to rely on left frontal cortical regions and has also been shown to be affected by lesions in the white matter, which may be seen as white matter hyperintensities (WMH) on magnetic resonance imaging. However, word fluency may be divided into two independent components, initial and late performance, separated in time [J Clin Exp Neuropsychol 1998;20:137-143]. The purpose of the current study was to investigate the relationship between the two components of FAS fluency performance and WMH. Patients varying in degree of memory impairment participated: Alzheimer's disease, mild cognitive impairment and subjective memory disorder. WMH were rated with the Scheltens scale in the periventricular and deep subcortical areas. Results demonstrated that WMH in this sample of patients may be summarized in two indices according to a principal factor analysis, one anterior factor mainly related to WMH in the frontal lobes and adjacent to ventricles, and a second posterior factor related to parietal and occipital WMH. The initial FAS performance was related to anterior WMH, in particular left frontal or lateral periventricular hyperintensities, whereas the late FAS performance was not related to any index of WMH.","Aged;Alzheimer Disease/ pathology/psychology;Brain/pathology;Cognition Disorders/ pathology/psychology;Factor Analysis, Statistical;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Memory;Memory Disorders/ pathology/psychology;Middle Aged;Neuropsychological Tests;Severity of Illness Index;Speech","Fernaeus, S. E.;Almkvist, O.;Bronge, L.;Ostberg, P.;Hellstrom, A.;Winblad, B.;Wahlund, L. O.",2001,Jan-Feb,51235,0,
4422,The Leukocentric Theory of Neurological Disorder: A Manifesto,"Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM. In addition, advances in brain imaging have revealed early, often prodromal, changes in WM structure in most forms of neurodegeneration including Alzheimer's, Huntingdon's and Parkinson's diseases as well as during normal cognitive decline and a variety of behavioral conditions. The significance of the early WM changes for the etiology of these diseases is largely unknown. Subtle, early changes in synaptic function may produce the prodromal WM changes evident in imaging, or WM and gray mater structures may undergo simultaneous reactions to the underlying disease process. However, there are rational mechanisms for the transmission of pathology from WM to gray matter and this article suggests an alternative hypothesis: that WM pathology precedes and to some extent is causal of synaptic dysfunction in many common neurological disorders. Neurological disorders that have their origin or their principle lesion in WM are here defined as ""leukopathologies"".",Axon;Glutamate;Neurodegeneration;Pathology;White matter,"Fern, R.",2017,Sep,,0,
4423,Anomalous White Matter Structure and the Effect of Age in Down Syndrome Patients,"BACKGROUND: Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. OBJECTIVE: The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. METHODS: Forty-five adult non-demented Down syndrome patients showing a wide age range (18-52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. RESULTS: Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. CONCLUSIONS: Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.",Accelerated aging;diffusion tensor imaging;magnetic resonance imaging;neurodegeneration,"Fenoll, R.;Pujol, J.;Esteba-Castillo, S.;de Sola, S.;Ribas-Vidal, N.;Garcia-Alba, J.;Sanchez-Benavides, G.;Martinez-Vilavella, G.;Deus, J.;Dierssen, M.;Novell-Alsina, R.;de la Torre, R.",2017,,,0,
4424,In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease,"Objective: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. Methods: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. Results: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. Conclusions: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.",adult;age;article;basal ganglion;brain cortex;cerebellum;cerebellum atrophy;clinical article;education;human;Huntington chorea;morphometrics;nerve degeneration;nuclear magnetic resonance imaging;priority journal;white matter,"Fennema-Notestine, C.;Archibald, S. L.;Jacobson, M. W.;Corey-Bloom, J.;Paulsen, J. S.;Peavy, G. M.;Gamst, A. C.;Hamilton, J. M.;Salmon, D. P.;Jernigan, T. L.",2004,,,0,
4425,"Associations between elevated homocysteine, cognitive impairment, and reduced white matter volume in healthy old adults","Objectives: Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not beenwell studied.Wereport these interrelationships innon demented, relatively healthy, community-dwelling olderadults froma single East Asianpopulation. Methods: Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than wellcontrolled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B (12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured. Results: Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t=-2.9, df = 223, p = 0.004) and lower speed of processing (β=-0.38, t=-2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated. Conclusion: In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level. © 2013 American Association for Geriatric Psychiatry.",,"Feng, L.;Isaac, V.;Sim, S.;Ng, T. P.;Krishnan, K. R. R.;Chee, M. W. L.",2013,February,,0,
4426,"APOE ε4, aging, and effects on white matter across the adult life span",,apolipoprotein E4;aging;Alzheimer disease;brain blood flow;episodic memory;fractional anisotropy;functional magnetic resonance imaging;genetic variability;hippocampus;human;letter;lifespan;oxygen blood level;posterior cingulate;task performance;white matter,"Felsky, D.;Voineskos, A. N.",2013,,,0,
4427,The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan,"Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.","0 (LDL-Receptor Related Proteins);0 (Membrane Transport Proteins);0 (RNA, Messenger);0 (SORL1 protein, human);Adolescent;Adult;Aged;Aged, 80 and over;Aging/genetics/metabolism;Alzheimer Disease/ genetics/ metabolism/pathology;Brain/growth & development/ metabolism/pathology;Child;Child, Preschool;Diffusion Tensor Imaging;Female;Genetic Predisposition to Disease;Humans;Infant;Infant, Newborn;LDL-Receptor Related Proteins/ genetics/ metabolism;Male;Membrane Transport Proteins/ genetics/ metabolism;Middle Aged;Polymorphism, Single Nucleotide;RNA, Messenger/metabolism;Young Adult","Felsky, D.;Szeszko, P.;Yu, L.;Honer, W. G.;De Jager, P. L.;Schneider, J. A.;Malhotra, A. K.;Lencz, T.;Ikuta, T.;Pipitone, J.;Chakravarty, M. M.;Lobaugh, N. J.;Mulsant, B. H.;Pollock, B. G.;Kennedy, J. L.;Bennett, D. A.;Voineskos, A. N.",2014,Oct,,0,4428
4428,The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan,"Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.Molecular Psychiatry advance online publication, 29 October 2013; doi:10.1038/mp.2013.142.",,"Felsky, D.;Szeszko, P.;Yu, L.;Honer, W. G.;De Jager, P. L.;Schneider, J. A.;Malhotra, A. K.;Lencz, T.;Ikuta, T.;Pipitone, J.;Chakravarty, M. M.;Lobaugh, N. J.;Mulsant, B. H.;Pollock, B. G.;Kennedy, J. L.;Bennett, D. A.;Voineskos, A. N.",2013,,,0,
4429,Cerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant,"The translocator protein, a microglial-expressed marker of neuroinflammation, has been implicated in Alzheimer's disease, which is characterized by alterations in vascular and inflammatory states. ATSPOvariant, rs6971, determines binding affinity of exogenous radioligandsin vivo; however, the effect of these altered binding characteristics on inflammatory and cerebrovascular biomarkers has not been assessed. In 2345 living subjects (Alzheimer's Disease Neuroimaging Initiative, n = 1330) and postmortem brain samples (Religious Orders Study and Memory and Aging Project, n = 1015), we analyzed effects of rs6971 on white matter hyperintensisites, cerebral infarcts, circulating inflammatory biomarkers, amyloid angiopathy, and microglial activation. We found that rs6971 does not alter translocator protein in a way that impacts cerebrovascular and inflammatory states known to be affected in dementia.",Alzheimer's;Mri;Microglia;genetics;inflammation;risk factors;white matter disease,"Felsky, D.;De Jager, P. L.;Schneider, J. A.;Arfanakis, K.;Fleischman, D. A.;Arvanitakis, Z.;Honer, W. G.;Pouget, J. G.;Mizrahi, R.;Pollock, B. G.;Kennedy, J. L.;Bennett, D. A.;Voineskos, A. N.",2016,Apr,10.1177/0271678x15626719,0,
4430,Comparison of automated brain segmentation using a brain phantom and patients with early Alzheimer's dementia or mild cognitive impairment,"Magnetic resonance imaging (MRI) and brain volumetry allow for the quantification of changes in brain volume using automatic algorithms which are widely used in both, clinical and scientific studies. However, studies comparing the reliability of these programmes are scarce and mainly involved MRI derived from younger healthy controls. This study evaluates the reliability of frequently used segmentation programmes (SPM, FreeSurfer, FSL) using a realistic digital brain phantom and MRI brain acquisitions from patients with manifest Alzheimer's disease (AD, n=34), mild cognitive impairment (MCI, n=60), and healthy subjects (n=32) matched for age and sex. Analysis of the brain phantom dataset demonstrated that SPM, FSL and FreeSurfer underestimate grey matter and overestimate white matter volumes with increasing noise. FreeSurfer calculated overall smaller brain volumes with increasing noise. Image inhomogeneity had only minor, non- significant effects on the results obtained with SPM and FreeSurfer 5.1, but had effects on the FSL results (increased white matter volumes with decreased grey matter volumes). The analysis of the patient data yielded decreasing volumes of grey and white matter with progression of brain atrophy independent of the method used. FreeSurfer calculated the largest grey matter and the smallest white matter volumes. FSL calculated the smallest grey matter volumes; SPM the largest white matter volumes. Best results are obtained with good image quality. With poor image quality, especially noise, SPM provides the best segmentation results. An optimised template for segmentation had no significant effect on segmentation results. While our findings underline the applicability of the programmes investigated, SPM may be the programme of choice when MRIs with limited image quality or brain images of elderly should be analysed.","Aged;Alzheimer Disease/ diagnosis/metabolism;Brain/metabolism/ pathology;Disease Progression;Female;Gray Matter/metabolism/pathology;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/metabolism;Phantoms, Imaging;Reproducibility of Results;White Matter/metabolism/pathology","Fellhauer, I.;Zollner, F. G.;Schroder, J.;Degen, C.;Kong, L.;Essig, M.;Thomann, P. A.;Schad, L. R.",2015,Sep 30,10.1016/j.pscychresns.2015.07.011,0,
4431,Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study,"Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.","Aged;Alzheimer Disease/pathology;Anisotropy;Brain/ pathology/ultrastructure;Cognition Disorders/ pathology;Female;Hippocampus/ pathology/ultrastructure;Humans;Hypercholesterolemia/complications/pathology;Hypertension/complications/pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychiatric Status Rating Scales;Risk Factors","Fellgiebel, A.;Wille, P.;Muller, M. J.;Winterer, G.;Scheurich, A.;Vucurevic, G.;Schmidt, L. G.;Stoeter, P.",2004,,10.1159/000077817,0,
4432,Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment,"Different processes like microvascular dysfunction, free radical toxicity, beta-amyloid deposits, and Wallerian degeneration can cause functionally relevant disturbances of cerebral neuronal networks by myelin degeneration. Color-coded diffusion-tensor-imaging (ccDTI) allows the structural identification and quantification of myelinated fiber tracts. Particularly, posterior cingulate fiber tracts, which are regarded as important neuronal substrates of the network representing memory processing can be localized only imprecisely by conventional magnetic resonance imaging techniques. The posterior cingulate bundles were assessed by ccDTI in 17 patients with amnestic mild cognitive impairment (MCI), 25 patients with Alzheimer's dementia (DAT), and 21 age-matched controls. Additionally, DTI values were correlated with memory performance in the delayed verbal recall test. Fractional anisotropy and mean diffusivity differed significantly between MCI and controls, as well as between DAT and controls. Performance in the delayed verbal recall test of the entire study group correlated significantly with posterior cingulate bundle anisotropy and diffusivity. Using ccDTI seems, hence, a favorable strategy to detect and quantify the structural integrity of posterior cingulate white matter in MCI. Alterations of DTI parameters substantiate the involvement of white matter pathology in the development of MCI. Moreover, ccDTI could serve as in vivo method to investigate age and disease-related myelin alterations as potential morphological substrates of cognitive dysfunction.","Aged;Alzheimer Disease/ pathology/physiopathology;Anisotropy;Cognition Disorders/ pathology/physiopathology;Diffusion Magnetic Resonance Imaging/instrumentation/ methods;Female;Gyrus Cinguli/ pathology/physiopathology;Hippocampus/physiopathology;Humans;Image Processing, Computer-Assisted/instrumentation/methods;Male;Memory Disorders/pathology/physiopathology/psychology;Middle Aged;Nerve Fibers, Myelinated/pathology;Neural Pathways/ pathology/physiopathology;Neuropsychological Tests;Predictive Value of Tests","Fellgiebel, A.;Muller, M. J.;Wille, P.;Dellani, P. R.;Scheurich, A.;Schmidt, L. G.;Stoeter, P.",2005,Aug-Sep,10.1016/j.neurobiolaging.2004.11.006,0,
4433,Alterations of mean diffusivity and fractional anisotropy in the posterior part of the cingulate fascicle. A diffusion tensor imaging study,"Background and Purpose: The aim of this study was the detection of diffusion tensor imaging-(DTI-) derived parameters mean diffusivity (MD) and fractional anisotropy (FA) in the posterior part of the cingulate fascicle in patients with mild cognitive impairment (MCI) which is commonly regarded as an early stage of Alzheimer's disease (AD). The posterior cingulate is an important part of the Papez circuit which subsumes necessary neural substrates of episodic memory. Decreases of posterior cingulate glucose metabolism corresponding to impaired memory performance could be demonstrated to indicate AD in MCI patients. Patients and Methods: After neuropsychological testing, DTI datasets were acquired in 17 MCI patients, 25 patients with Alzheimer dementia, and 21 age-matched healthy controls. Placement of regions of interest (ROIs) into the posterior part of the cingulated fiber bundle was performed on the basis of color-coded maps of the white matter tracts which had been calculated from the diffusion tensors. Results: Significant elevations of MD and reductions of FA were found in MCI and AD patients compared to controls. In addition, pathologic changes of diffusion characteristics (MD and FA) were significantly correlated with impaired memory function. Conclusion: The finding of an elevation of MD and reduction of FA might be regarded as an early MR indicator for the development of AD. © Urban & Vogel.",,"Fellgiebel, A.;Mazanek, M.;Dellani, P. R.;Müller, M. J.;Scheurich, A.;Tropine, A.;Schmidt, L. G.;Stoeter, P.",2005,Jun,,0,
4434,Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease,"BACKGROUND: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. OBJECTIVES: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. METHODS: Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment-normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i. e., hippocampal, cortical gray matter, and CSF volumes). RESULTS: Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. CONCLUSIONS: Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.","Aged;Atrophy/pathology;Brain/pathology;Brain Ischemia/*pathology;Cerebral Cortex/*pathology;Dementia, Vascular/*pathology;Female;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Stroke/*pathology","Fein, G.;Di Sclafani, V.;Tanabe, J.;Cardenas, V.;Weiner, M. W.;Jagust, W. J.;Reed, B. R.;Norman, D.;Schuff, N.;Kusdra, L.;Greenfield, T.;Chui, H.",2000,Dec 12,,0,
4435,The spectrum of mutations for CADASIL diagnosis,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations of the Notch3 gene at the chromosome locus 19p13. The clinical spectrum includes recurrent ischaemic episodes, cognitive deficits, migraine and psychiatric disorders. The histopathological hallmark of CADASIL is accumulation of electron dense granules (GOM) in the media of arterioles. MRI reveals extensive cerebral white matter lesions and subcortical infarcts. CADASIL was initially thought to be a rare disorder, but increasing numbers of families have been identified; therefore, it is likely that CADASIL is still largely underdiagnosed. Here we report an update on mutations of the Notch3 gene and some information on the pathogenesis of the disease. © Springer-Verlag Italia 2005.",Notch3 receptor;artery media;article;brain cortex;brain infarction;brain injury;brain ischemia;CADASIL;cerebrovascular disease;chromosome 19p;clinical feature;cognitive defect;family study;gene locus;gene mutation;histopathology;human;medical information;mental disease;migraine;molecular genetics;nuclear magnetic resonance imaging;recurrent disease;white matter,"Federico, A.;Bianchi, S.;Dotti, M. T.",2005,,,0,
4436,Computer-aided detection of cerebral microbleeds in susceptibility-weighted imaging,"Susceptibility-weighted imaging (SWI) is recognized as the preferred MRI technique for visualizing cerebral vasculature and related pathologies such as cerebral microbleeds (CMBs). Manual identification of CMBs is time-consuming, has limited reliability and reproducibility, and is prone to misinterpretation. In this paper, a novel computer-aided microbleed detection technique based on machine learning is presented: First, spherical-like objects (potential CMB candidates) with their corresponding bounding boxes were detected using a novel multi-scale Laplacian of Gaussian technique. A set of robust 3-dimensional Radon- and Hessian-based shape descriptors within each bounding box were then extracted to train a cascade of binary random forests (RF). The cascade consists of consecutive independent RF classifiers with low to high posterior probability constraints to handle imbalanced training sets (CMBs and non-CMBs), and to progressively improve detection rates. The proposed method was validated on 66 subjects whose CMBs were manually stratified into ""possible"" and ""definite"" by two medical experts. The proposed technique achieved a sensitivity of 87% and an average false detection rate of 27.1 CMBs per subject on the ""possible and definite"" set. A sensitivity of 93% and false detection rate of 10 CMBs per subject was also achieved on the ""definite"" set. The proposed automated approach outperforms state of the art methods, and promises to enhance manual expert screening. Benefits include improved reliability, minimization of intra-rater variability and a reduction in assessment time.",,"Fazlollahi, A.;Meriaudeau, F.;Giancardo, L.;Villemagne, V. L.;Rowe, C. C.;Yates, P.;Salvado, O.;Bourgeat, P.",2015,1,,0,
4437,Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment,"Although both morphologic cerebral damage and cognitive dysfunction are known to occur in patients on chronic hemodialysis (CHD) their extent and possible relation have been rarely studied. We therefore performed magnetic resonance imaging of the brain and neuropsychological testing in 30 consecutive CHD patients (mean age 58 years; range 37-69) and in an equal number of asymptomatic volunteers matched for age, sex and major cerebrovascular risk factors. Twenty-four (80%) of the CHD patients were demented according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IIIR and their mean scores on the Mini Mental State Examination (22.9 +/- 4 vs. 27.9 +/- 1.4; p < 0.001) and Mattis Dementia Rating Scale (112.3 +/- 21.5 vs. 141.9 +/- 2.3); p < 0.001) were significantly lower than those of controls. The brains of CHD patients showed significantly more atrophy on visual rating and semiquantitative morphometric measures. Multiple lacunes or confluent white matter hyperintensities predominated in 10 (33%) patients, three showed territorial infarcts and two a combination of both. Clinically these findings were unexpected in almost half of individuals. Marked cognitive impairment was associated with more extensive enlargement of the third ventricle (5.8 +/- 1.8 vs. 7.3 +/- 2 mm; p < 0.04) and the temporal horns (3.5 +/- 1.6 vs. 5.1 +/- 1.8 mm; p < 0.02) but not with the presence of cerebral ischemic lesions or any difference in laboratory data. These results call attention to a very high rate of cerebral damage in individuals undergoing CHD and suggest brain degeneration of probably toxic-metabolic etiology to be associated with severe cognitive impairment of these patients.","Adult;Aged;Brain Damage, Chronic/ diagnosis/etiology;Cognition Disorders/ diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Renal Dialysis/ adverse effects;Risk Factors","Fazekas, G.;Fazekas, F.;Schmidt, R.;Kapeller, P.;Offenbacher, H.;Krejs, G. J.",1995,Dec,,0,
4438,The relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease,"To further elucidate the relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease (AD) we performed a case-control comparison between 30 consecutive patients with probable AD (age range 49-76, mean 65 years) and 60 asymptomatic volunteers matched for age, sex, and major cerebrovascular risk factors. We used a 1.5T magnet and determined the extent of morphologic abnormalities both by visual grading and measurement. AD patients showed comparable grades of deep/subcortical white matter hyperintensities (WMH) and a similar extent of the total WMH area as controls (3.3 cm2 +/- 8.8 vs. 2.0 cm2 +/- 4.6). They had significantly more often a ""halo' of periventricular hyperintensity (PVH) (p < 0.0005) and an increased mean PVH thickness (3.0 mm +/- 1.9 vs. 1.3 mm +/- 1.2; p < 0.001). This PVH thickness correlated significantly with measures of ventricular enlargement. While univariate logistic regression also suggested a significant association of PVH thickness with a diagnosis of AD this association was lost against atrophy measures in a multivariate analysis. Our results confirm a significantly greater extent of PVH in AD patients than controls even when matched for cerebrovascular risk factors. However, this abnormality was not independently related to the disease but rather appears to be an epiphenomenon of brain atrophy.",Aged;Alzheimer Disease/*diagnosis/pathology;Atrophy;Corpus Callosum/pathology;Female;Humans;*Magnetic Resonance Imaging;Male;Matched-Pair Analysis;Middle Aged;Nerve Fibers/pathology;Predictive Value of Tests,"Fazekas, F.;Kapeller, P.;Schmidt, R.;Offenbacher, H.;Payer, F.;Fazekas, G.",1996,Oct,,0,
4439,MRI in acute cerebral ischemia of theyoung the stroke in young fabry patients (sifap1) study,"Objective: We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. Methods: We analyzed the scans of 2,979 patients (aged 18-55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18-34, 35-44, and 45-55 years.We compared age-and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. Results: Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%).B Conclusions: Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older. © 2013 American Academy of Neurology.",,"Fazekas, F.;Enzinger, C.;Schmidt, R.;Dichgans, M.;Gaertner, B.;Jungehulsing, R. M. G. J.;Hennerici, M. G.;Heuschmann, P.;Holzhausen, M.;Kaps, M.;Kessler, C.;Martus, P.;Putaala, J.;Ropele, S.;Tanislav, C.;Tatlisumak, T.;Norrving, B.;Rolfs, A.",2013,26,,0,
4440,MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging,"The type, frequency, and extent of MR signal abnormalities in Alzheimer's disease and normal aging are a subject of controversy. With a 1.5-MR unit we studied 12 Alzheimer patients, four subjects suffering from multiinfarct dementia and nine age-matched controls. Punctate or early confluent high-signal abnormalities in the deep white matter, noted in 60% of both Alzheimer patients and controls, were unrelated to the presence of hypertension or other vascular risk factors. A significant number of Alzheimer patients exhibited a more extensive smooth 'halo' of periventricular hyperintensity when compared with controls (p = .024). Widespread deep white-matter hyperintensity (two patients) and extensive, irregular periventricular hyperintensity (three patients) were seen in multiinfarct dementia. Areas of high signal intensity affecting hippocampal and sylvian cortex were also present in five Alzheimer and two multiinfarct dementia patients, but absent in controls. Discrete, small foci of deep whitematter hyperintensity are not characteristic of Alzheimer's disease nor do they appear to imply a vascular cause for the dementing illness. The frequently observed 'halo' of periventricular hyperintensity in Alzheimer's disease may be of diagnostic importance. High-signal abnormalities in specific cortical regions are likely to reflect disease processes localized to those structures.",age;aging;Alzheimer disease;brain infarction;central nervous system;clinical article;clinical study;computer analysis;dementia;diagnosis;human;normal human;nuclear magnetic resonance imaging;priority journal,"Fazekas, F.;Chawluk, J. B.;Alavi, A.",1987,,,0,
4441,"Comparison of CT, MR, and PET in Alzheimer's dementia and normal aging","We compared the findings of computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) scans of glucose metabolism in 30 patients with clinically diagnosed Alzheimer's Disease (DAT) to those noted in 25 age-matched normal controls. Mean ratings of cortical and ventricular atrophy on CT and of metabolic abnormality on PET were significantly different (p less than 0.001 and p less than 0.0001, respectively) between two subject groups, however, there was a considerable overlap in reading of cortical atrophy. CT hypodensities were present in 17% of DAT patients and 12% of controls. MR revealed numerous additional periventricular and deep white matter signal changes. Neither hypodensities nor hyperintensities were correlated with PET abnormalities. Although, not infrequently, hypometabolic areas on PET scans corresponded to atrophic regions on anatomic images, they also occurred without such changes. Interestingly, cortical high signal intensity seen on MRI was frequently observed to be associated with areas of hypometabolism. Our results suggest that PET may be the most sensitive modality for detecting cortical involvement in DAT.","Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ diagnosis/radiography/radionuclide imaging;Brain/pathology/radiography/radionuclide imaging;Glucose;Humans;Magnetic Resonance Imaging;Middle Aged;Tomography, Emission-Computed;Tomography, X-Ray Computed","Fazekas, F.;Alavi, A.;Chawluk, J. B.;Zimmerman, R. A.;Hackney, D.;Bilaniuk, L.;Rosen, M.;Alves, W. M.;Hurtig, H. I.;Jamieson, D. G.;et al.",1989,Oct,,0,
4442,Magnetic resonance spectroscopy and brain volumetry in mild cognitive impairment. A prospective study,"OBJECTIVE: To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD). METHODS: Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD. RESULTS: After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate+glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%. CONCLUSION: Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.",Alzheimer's disease;Brain volumetry;Magnetic resonance spectroscopy;Mild cognitive impairment,"Fayed, N.;Modrego, P. J.;Garcia-Marti, G.;Sanz-Requena, R.;Marti-Bonmati, L.",2017,May,,0,
4443,Correlation of findings in advanced MR techniques with global severity scales in patients with some grade of cognitive impairment,"INTRODUCTION: Some previous studies in patients with mild cognitive impairment and Alzheimer's disease have probed changes in the results of (1)H magnetic resonance spectroscopy and perfusion- and diffusion-weighted imaging. The purpose of this work was to correlate the results of perfusion- and diffusion-weighted imaging and magnetic resonance spectroscopy with the results of two global severity scales in cognitive impairment: the clinical dementia rating (CDR) and the global deterioration scale (GDS). PATIENTS AND METHODS: We evaluated 87 patients with cognitive impairment of diverse grade (35 men and 52 women; mean age, 70.2 +/- 8.5 years old). All patients were evaluated by a neurological team in our hospital. They applied both global severity scales (CDR and GDS) and referred the patients to our diagnostic imaging department to make a cerebral magnetic resonance imaging study and studies of diffusion- and perfusion-weighted imaging and magnetic resonance spectroscopy. We excluded patients with history of Parkinson's disease, frontotemporal dementia, cerebrovascular disease, intracranial tumors, hydrocephaly, epilepsy, alcoholism and psychiatric disorders. Magnetic resonance spectroscopy was carried out in the left occipital cortex and in the posterior cingulate gyrus. The evaluated metabolites were N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI). After diffusion-weighted imaging, we calculated apparent diffusion coefficient values in the region of interest located in hippocampi, white matter of temporal lobes, occipital lobes, parietal lobes, frontal lobes and posterior cingulate gyrus of both hemispheres. In perfusion-weighted imaging, we calculated the relative cerebral blood volume in hippocampi, gray matter of frontal lobes, occipital lobes, temporoparietal regions, posterior cingulate gyri and somatic-sensorial cortex. We used Spearman coefficient to analyse the correlation among the different factors. Statistical analysis was made with SPSS 14 software. RESULTS: We found 33 patients with Alzheimer's disease and 54 with mild cognitive impairment. The Spearman coefficient had statistical significance in the correlation of CDR and GDS (R(2)=0.596, p<0.001). Magnetic resonance spectroscopy showed a good correlation between ratios of NAA/Cr and NAA/mI with CDR and GDS in both evaluated regions and a weak correlation between Cho/Cr in the left occipital lobe and GDS. In diffusion-weighted imaging, we found a weak correlation between GDS and apparent diffusion coefficient values in hippocampi, temporal lobes, left frontal lobe and left occipital lobe. Finally, perfusion showed a weak correlation between GDS and relative cerebral blood volume in occipital lobes and posterior cingulate gyrus. CONCLUSION: In patients with cognitive impairment, there is a good correlation between CDR and GDS. The tool that showed the closest correlation with the clinical scales (CDR and GDS) was magnetic resonance spectroscopy in the left occipital cortex and posterior cingulate gyrus. Perfusion- and diffusion-weighted imaging are tools with a weak correlation with clinical scales, GDS being unique that gave us significant statistical results; this could be explained by the major number of items considered for cognitive impairment (GDS 2 and 3) compared with CDR (CDR 0.5). Magnetic resonance spectroscopy can be used in the diagnostic, following and evaluation of the response to the treatment in patients with cognitive impairment (mild cognitive impairment and Alzheimer's disease), complementing the information obtained in the clinical evaluation.","Aged;Aged, 80 and over;Alzheimer Disease/classification/diagnosis;Brain/pathology;Cognition Disorders/ classification/ diagnosis;Female;Humans;Magnetic Resonance Spectroscopy/methods;Male;Middle Aged;Prospective Studies;Severity of Illness Index","Fayed, N.;Davila, J.;Oliveros, A., Jr.;Medrano, J.;Castillo, J.",2010,Mar,10.1179/174313209x405164,0,
4444,"High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of aggregated tau in Alzheimer's disease and progressive supranuclear palsy: synthesis, preclinical evaluation, and lead selection","Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials.","Alzheimer Disease/metabolism/ radionuclide imaging;Amyloid beta-Peptides/metabolism;Animals;Autoradiography;Brain/metabolism/radionuclide imaging;Carbon Radioisotopes/chemistry/pharmacokinetics;Drug Evaluation, Preclinical;Fluorine Radioisotopes/chemistry/pharmacokinetics;Humans;Lansoprazole/chemistry/pharmacokinetics;Mice;Peptide Fragments/metabolism;Positron-Emission Tomography/methods;Primates;Radiopharmaceuticals/chemical synthesis/chemistry/pharmacokinetics;Rats;Supranuclear Palsy, Progressive/metabolism/ radionuclide imaging;tau Proteins/metabolism","Fawaz, M. V.;Brooks, A. F.;Rodnick, M. E.;Carpenter, G. M.;Shao, X.;Desmond, T. J.;Sherman, P.;Quesada, C. A.;Hockley, B. G.;Kilbourn, M. R.;Albin, R. L.;Frey, K. A.;Scott, P. J.",2014,Aug 20,10.1021/cn500103u,0,
4445,Early diagnosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): the role of MRI,"The aim of our work was to evaluate the early presence of white matter changes on magnetic resonance imaging (MRI) in young asymptomatic children of patients with full-blown cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in whom DNA analysis revealed a Notch3 Cys146Tyr missense mutation on chromosome 19. Brain MRI was performed in all subjects using axial and coronal spin-echo proton density and T2-weighted images, axial fluid-attenuated inversion recovery (FLAIR) and sagittal and axial T1-weighted images. In asymptomatic subjects with Notch3 gene mutation, MRI showed small T2 hyperintense foci in periventricular and subcortical white matter. Routine use of MRI in the initial phases of a CADASIL diagnostic work up and the subsequent recognition of early abnormal findings in asymptomatic subjects may lead to prompt diagnosis of the disease in these patients. Moreover, these findings suggest that genetic screening is warranted in the presence of a suspect clinical history with specific MRI abnormalities.","Adult;Brain/pathology;CADASIL/ diagnosis/genetics;Child;Chromosomes, Human, Pair 19;Cysteine;Early Diagnosis;Humans;Magnetic Resonance Imaging;Mutation, Missense;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface/genetics;Receptors, Notch;Tyrosine","Fattapposta, F.;Restuccia, R.;Pirro, C.;Malandrini, A.;Locuratolo, N.;Amabile, G.;Bianco, F.",2004,Oct-Dec,,0,
4446,MR Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus,"BACKGROUND AND PURPOSE: Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals. MATERIALS AND METHODS: MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20). CONCLUSIONS: This study demonstrates increased brain stiffness in patients with normal pressure hydrocephalus compared with age- and sex-matched healthy controls; these findings should motivate future studies investigating the use of MR elastography for this condition and the efficacy of shunt therapy.",,"Fattahi, N.;Arani, A.;Perry, A.;Meyer, F.;Manduca, A.;Glaser, K.;Senjem, M. L.;Ehman, R. L.;Huston, J.",2016,Mar,10.3174/ajnr.A4560,0,
4447,Retained executive abilities in mild cognitive impairment are associated with increased white matter network connectivity,"PURPOSE: To describe structural network differences in individuals with mild cognitive impairment (MCI) with high versus low executive abilities, as reflected by measures of white matter connectivity using diffusion tensor imaging (DTI). MATERIALS AND METHODS: This was a retrospective, cross-sectional study. Of the 128 participants from the Alzheimer's Disease Neuroimaging Initiative database who had both a DTI scan as well as a diagnosis of MCI, we used an executive function score to classify the top 15 scoring patients as high executive ability, and the bottom-scoring 16 patients as low executive ability. Using a regions-of-interest-based analysis, we constructed networks and calculated graph theory measures on the constructed networks. We used automated tractography in order to compare differences in major white matter tracts. RESULTS: The high executive ability group yielded greater network size, density and clustering coefficient. The high executive ability group reflected greater fractional anisotropy bilaterally in the inferior and superior longitudinal fasciculi. CONCLUSIONS: The network measures of the high executive ability group demonstrated greater white matter integrity. This suggests that white matter reserve may confer greater protection of executive abilities. Loss of this reserve may lead to greater impairment in the progression to Alzheimer's disease dementia. KEY POINTS: * The MCI high executive ability group yielded a larger network. * The MCI high executive ability group had greater FA in numerous tracts. * White matter reserve may confer greater protection of executive abilities. * Loss of executive reserve may lead to greater impairment in AD dementia.",Cognitive dysfunction;Dementia;Diffusion tensor imaging;Neuroanatomy;White matter,"Farrar, D. C.;Mian, A. Z.;Budson, A. E.;Moss, M. B.;Koo, B. B.;Killiany, R. J.;Alzheimer's Disease Neuroimaging, Initiative",2018,Jan,,0,
4448,"Neuroimaging of a New Familial Disorder; Ataxia, Chorea, Seizures, and Dementia","The neuroimaging findings observed in a family with a previously reported syndrome of progressive ataxia, chorea, seizures, and dementia include an unusual combination: (1) bilateral basal ganglia calcification limited to the globus pallidus on brain computed tomography; (2) abnormal focal and diffuse areas of increased signal intensity in the cerebral white matter on brain magnetic resonance imaging; and (3) mild to moderate degrees of atrophy of the cerebrum, cerebellum, and brainstem. These neuroimaging findings define further this new clinical entity.",,"Farmer, T. W.;Wingfield, M. S.;Jacobson, P. L.;Katchinoft, B. L.;Lynch, S. A.;Curnes, J. T.",1991,1,,0,
4449,Linking white matter and deep gray matter alterations in premanifest Huntington disease,"Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.",adult;article;atrophy;controlled study;diffusion tensor imaging;effect size;female;gray matter;hippocampus;human;Huntington chorea;major clinical study;male;morphometrics;mutation;nuclear magnetic resonance imaging;nucleus accumbens;priority journal;putamen;thalamus;tractography;white matter,"Faria, A. V.;Ratnanather, J. T.;Tward, D. J.;Lee, D. S.;Van Den Noort, F.;Wu, D.;Brown, T.;Johnson, H.;Paulsen, J. S.;Ross, C. A.;Younes, L.;Miller, M. I.",2016,,,0,
4450,Study of enhanced depth imaging optical coherence tomography in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings. Methods: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman’s correlation was used to investigate the correlation between retinal vessel changes and MRI lesions. Results: In CADASIL patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 μm) were significantly lower than that in controls (P < 0.001, P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 μm), venous inner (128.99 ± 13.62 μm) and outer diameter (164.82 ± 14.77 μm), and mean arterial (19.13 ± 1.85 μm) and venous (17.91 ± 2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023, P = 0.004, P < 0.001, P < 0.001, respectively). Arterial inner diameter (rs = −0.39, P = 0.044), AVRin (rs = −0.65, P < 0.001), and AVRout (rs = −0.56, P = 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P = 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P = 0.002), outer diameter (rs = 0.47, P = 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs = −0.52, P = 0.007) and AVRout (rs = −0.40, P = 0.048) showed a negative correlation with the number of CMBs. Conclusions: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.",adult;artery diameter;article;blood vessel wall;brain hemorrhage;CADASIL;choroidal thickness;clinical article;controlled study;Fazekas score;female;gene mutation;genotype phenotype correlation;human;male;mean arterial pressure;nuclear magnetic resonance imaging;optical coherence tomography;retina blood vessel;scoring system;vein diameter;white matter lesion,"Fang, X. J.;Yu, M.;Wu, Y.;Zhang, Z. H.;Wang, W. W.;Wang, Z. X.;Yuan, Y.",2017,,10.4103/0366-6999.204935,0,
4451,Disrupted Structural Brain Network in AD and aMCI: A Finding of Long Fiber Degeneration,"Although recent evidence has emerged that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients show both regional brain abnormalities and topological degeneration in brain networks, our understanding of the effects of white matter fiber aberrations on brain network topology in AD and aMCI is still rudimentary. In this study, we investigated the regional volumetric aberrations and the global topological abnormalities in AD and aMCI patients. The results showed a widely distributed atrophy in both gray and white matters in the AD and aMCI groups. In particular, AD patients had weaker connectivity with long fiber length than aMCI and normal control (NC) groups, as assessed by fractional anisotropy (FA). Furthermore, the brain networks of all three groups exhibited prominent economical small-world properties. Interestingly, the topological characteristics estimated from binary brain networks showed no significant group effect, indicating a tendency of preserving an optimal topological architecture in AD and aMCI during degeneration. However, significantly longer characteristic path length was observed in the FA weighted brain networks of AD and aMCI patients, suggesting dysfunctional global integration. Moreover, the abnormality of the characteristic path length was negatively correlated with the clinical ratings of cognitive impairment. Thus, the results therefore suggested that the topological alterations in weighted brain networks of AD are induced by the loss of connectivity with long fiber lengths. Our findings provide new insights into the alterations of the brain network in AD and may indicate the predictive value of the network metrics as biomarkers of disease development.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology;Analysis of Variance;Brain/*pathology;Brain Mapping;Case-Control Studies;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/*pathology;Neural Pathways/*pathology;White Matter/*pathology","Fang, R.;Yan, X. X.;Wu, Z. Y.;Sun, Y.;Yin, Q. H.;Wang, Y.;Tang, H. D.;Sun, J. F.;Miao, F.;Chen, S. D.",2015,,,0,
4452,Brain atrophy in middle-aged type 2 diabetes with and without microvascular complications,"BACKGROUND: The rapid rise in type 2 Diabetes Mellitus (T2DM) among young adults makes it important to understand the brain structural changes at a pre-senile stage. This study is to examine global and regional brain atrophy in middle-aged adults with T2DM, with a specific focus on those without clinical evidence of microvascular complications. METHODS: 66 dementia-free middle-aged subjects (40 T2DM and 26 healthy volunteers (HVs)) were recruited. Patients were grouped according to the presence (T2DM-C, n=20) or absence (T2DM-NC, n=20) of diabetic microvascular complications. Global brain volume (including grey matter [GM] and white matter [WM]) was calculated based on voxel-based morphometry analysis. Regional GM volumes were further extracted using Anatomical Automatic Labeling template. RESULTS: There was a significant difference in global brain volume among groups (ANOVA, P=0.003). Lower global brain volume was observed in T2DM-C patients than in T2DM-NC patients (0.720[0.024] vs. 0.736[0.021], P=0.032) and HVs (0.720[0.024] vs. 0.743[0.019], P=0.001), respectively. Further regional analysis showed there was significant GM atrophy in the right Rolandic operculum (t=3.42, P=0.001) and right superior temporal gyrus (t=2.803, P=0.007) in T2DM-NC patients compared with age- and sex-matched HVs. CONCLUSIONS: Brain atrophy is present in dementia-free middle-aged adults with T2DM. Regional brain atrophy appears to be developing even in subgroup that shows no clinical evidence of microvascular disturbances. The brain seems to be particularly vulnerable to metabolic disorders prior to peripheral microvascular pathologies associated with other target organs.",Atrophy;Brain;Magnetic Resonance Imaging;Middle Aged;Type 2 Diabetes Mellitus,"Fang, F.;Zhan, Y. F.;Zhuo, Y. Y.;Yin, D. Z.;Li, K. A.;Wang, Y. F.",2018,Jan 30,,0,
4453,[Neuro-specific enolase in acute ischemic stroke and related dementia patients],Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in patients with acute ischemic stroke as compared with the controls. The altered CSF NSE levels were well correlated with the infarct size in CT scan. The CSF NSE levels were higher in 6-patients who were diagnosed as multi-infarct dementia (MID) after 6-month follow-up than in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE for dementia related to ischemic stroke is worth further studying.,"Aged;Biomarkers/cerebrospinal fluid;Brain/pathology;Cerebral Infarction/*enzymology/pathology;Dementia, Multi-Infarct/*enzymology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Phosphopyruvate Hydratase/*cerebrospinal fluid","Fang, D.;Li, Y.;Wang, X.;Yang, Z.",1995,Dec,,0,
4454,Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff sydrome,"Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure-function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS. Copyright © 2004 INS.",alcohol;adult;aged;alcoholism;Alzheimer disease;anterograde amnesia;article;brain cortex;brain function;clinical article;controlled study;correlation analysis;disease association;disease severity;female;hippocampus;human;information processing;intelligence test;Korsakoff psychosis;limbic system;male;memory disorder;mental performance;neuroanatomy;neuropsychological test;nuclear magnetic resonance imaging;priority journal;recall;statistical analysis;white matter;word recognition,"Fama, R.;Marsh, L.;Sullivan, E. V.",2004,,,0,
4455,Dissociation of remote and anterograde memory impairment and neural correlates in alcoholic Korsakoff syndrome,"Alcoholic Korsakoff's syndrome (KS) is marked by remote memory impairment together with characteristic profound anterograde memory deficits. Despite previous studies of memory processes in KS, questions remain regarding the nature and severity of these impairments and identification of brain systems that underlie these different memory impairments. This study examined remote and anterograde memory function in 5 KS patients in comparison with 8 patients with Alzheimer's disease (AD) and 24 normal control subjects (NC). In addition, relationships between memory performance and regional brain volumes were examined in the KS group. Overall, the KS group showed severe impairment on both remote and anterograde memory measures, performing at the level of the AD group on most measures. Differences were observed on the pattern of temporal gradient for verbal recognition, with KS exhibiting a more steeply graded rate of decline over the most recent period examined. Severity of the remote memory deficit in KS was not associated with severity of anterograde memory deficit. Examination of brain structure-function relationships in the KS subjects revealed that photo naming of remote historical information was related to posterior cortical white matter volumes but not hippocampal volumes; sequencing was related to prefrontal but not hippocampal volumes. By contrast, a measure of anterograde memory for nonverbal visual material showed a relationship to hippocampal but not regional cortical white matter volumes. This set of dissociations, which parallels that observed in our earlier study of AD, is now documented in KS and provides further evidence that these separate cortical and limbic brain systems are principal neural substrates of the remote and anterograde memory and sequencing deficits in KS.","Aged;Alcohol Amnestic Disorder/*complications;Amnesia, Anterograde/*etiology;Brain/*pathology/*physiopathology;Dissociative Disorders/*etiology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests/statistics & numerical data;Pattern Recognition, Visual/physiology;Problem Solving/physiology;Time Factors","Fama, R.;Marsh, L.;Sullivan, E. V.",2004,May,10.1017/s135561770410310x,0,
4456,A whole brain MR spectroscopy study from patients with Alzheimer's disease and mild cognitive impairment,"Brain damage in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is widespread with involvement of large portions of the neocortex and the subcortical white matter. A quantitative measure of neuronal damage of the entire brain might be valuable in the context of large-scale, longitudinal studies of these patients. This study investigated the extent of neuroaxonal injury of patients with AD and MCI using a novel unlocalized proton magnetic resonance spectroscopy ((1)H-MRS) technique, which allows quantification of the concentration of N-acetylaspartate from the whole of the brain tissue (WBNAA). Conventional brain MRI and WBNAA were obtained from 28 AD patients, 27 MCI patients and 25 age-matched controls. Normalized brain volume (NBV) was also measured using an automated segmentation technique. WBNAA and NBV showed a significant heterogeneity between groups (P < 0.001). WBNAA concentration was different between controls and MCI patients (P = 0.003), but not between MCI and AD patients (P = 0.33). NBV differed both between controls and MCI patients (P = 0.02) and between MCI and AD patients (P = 0.03). A multivariate regression model retained WBNAA as the best MRI predictor of the Mini Mental State Examination score (P = 0.001). Significant neuronal damage, which is related to the extent of cognitive decline, can be quantified in the whole brain tissue of patients with AD, using a novel (1)H-MRS approach. The demonstration in patients with MCI of MR structural and metabolic findings, intermediate between those of healthy volunteers and those of AD patients, indicates that neuronal damage is already evident and widespread in individuals with MCI before they are clinically demented.",Aged;Alzheimer Disease/*pathology/*psychology;Aspartic Acid/*analogs & derivatives/metabolism;Atrophy;Brain/*pathology;Brain Chemistry;Cognition Disorders/*pathology/*psychology;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Psychiatric Status Rating Scales;Reference Values,"Falini, A.;Bozzali, M.;Magnani, G.;Pero, G.;Gambini, A.;Benedetti, B.;Mossini, R.;Franceschi, M.;Comi, G.;Scotti, G.;Filippi, M.",2005,Jul 15,10.1016/j.neuroimage.2005.03.005,0,
4457,Non-Gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer's disease,"We report the first application of a novel diffusion-based MRI method, called diffusional kurtosis imaging (DKI), to investigate changes in brain tissue microstructure in patients with mild cognitive impairment (MCI) and AD and in cognitively intact controls. The subject groups were characterized and compared in terms of DKI-derived metrics for selected brain regions using analysis of covariance with a Tukey multiple comparison correction. Receiver operating characteristic (ROC) and binary logistic regression analyses were used to assess the utility of regional diffusion measures, alone and in combination, to discriminate each pair of subject groups. ROC analyses identified mean and radial kurtoses in the anterior corona radiata as the best individual discriminators of MCI from controls, with the measures having an area under the ROC curve (AUC) of 0.80 and 0.82, respectively. The next best discriminators of MCI from controls were diffusivity and kurtosis (both mean and radial) in the prefrontal white matter (WM), with each measure having an AUC between 0.77 and 0.79. Finally, the axial diffusivity in the hippocampus was the best overall discriminator of MCI from AD, having an AUC of 0.90. These preliminary results suggest that non-Gaussian diffusion MRI may be beneficial in the assessment of microstructural tissue damage at the early stage of MCI and may be useful in developing biomarkers for the clinical staging of AD.","Aged;Algorithms;Alzheimer Disease/ complications/ pathology;Brain/ pathology;Data Interpretation, Statistical;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Male;Mild Cognitive Impairment/ complications/ pathology;Normal Distribution;Pattern Recognition, Automated/methods;Reproducibility of Results;Sensitivity and Specificity","Falangola, M. F.;Jensen, J. H.;Tabesh, A.;Hu, C.;Deardorff, R. L.;Babb, J. S.;Ferris, S.;Helpern, J. A.",2013,Jul,10.1016/j.mri.2013.02.008,0,
4458,Symptomatic white matter changes in mild traumatic brain injury resemble pathologic features of early Alzheimer dementia,"PURPOSE: To evaluate white matter integrity in patients with mild traumatic brain injury (TBI) who did not have morphologic abnormalities at conventional magnetic resonance (MR) imaging with diffusion-tensor imaging to determine any relationship between patterns of white matter injury and severity of postconcussion symptoms. MATERIALS AND METHODS: The institutional review board approved this study, with waiver of informed consent. Diffusion-tensor images from 64 consecutive patients with mild TBI obtained with conventional MR imaging were evaluated retrospectively. Fractional anisotropy (FA) maps were generated as a measure of white matter integrity. All patients underwent a neurocognitive evaluation. Correlations between skeletonized FA values in white matter, total concussion symptom score, and findings of sleep and wake disturbances were analyzed with regression analysis that used tract-based spatial statistics. RESULTS: Total concussion symptom scores varied from 2 to 97 (mean +/- standard deviation, 32.7 +/- 24.4), with 34 patients demonstrating sleep and wake disturbances. Tract-based spatial statistics showed a significant correlation between high total concussion symptom score and reduced FA at the gray matter-white matter junction (P < .05), most prominently in the auditory cortex (P < .05). FA in the parahippocampal gyri was significantly decreased in patients with sleep and wake disturbances relative to patients without such disturbances (0.26 and 0.37, respectively; P < .05). CONCLUSION: The distribution of white matter abnormalities in patients with symptomatic mild TBI is strikingly similar to the distribution of pathologic abnormalities in patients with early Alzheimer dementia, a finding that may help direct research strategies.","Adolescent;Adult;Alzheimer Disease/ epidemiology/ pathology;Brain Concussion/ epidemiology/ pathology;Child;Comorbidity;Female;Humans;Incidence;Magnetic Resonance Imaging/ statistics & numerical data;Male;Nerve Fibers, Myelinated/ pathology;Pennsylvania/epidemiology;Reproducibility of Results;Risk Assessment;Sensitivity and Specificity;Young Adult","Fakhran, S.;Yaeger, K.;Alhilali, L.",2013,Oct,10.1148/radiol.13122343,0,
4459,Dystonia in AIDS: Report of four cases,"Dystonia is a rare complication of acquired immune deficiency syndrome (AIDS). We report four such cases related to three different causes. Cases 1 and 2 both developed dystonia secondary to biopsy-proven progressive multifocal leukoencephalopathy. One had left arm dystonia, whereas the other had bilateral upper limb dystonia. One patient had associated akinesia and rigidity. Imaging demonstrated frontal and/or parietal white matter lesions but no basal ganglia abnormalities. Case 3 developed hemidystonia and cervical dystonia from biopsyproven toxoplasmosis with a lesion in the thalamus. Case 4 suffered from AIDS dementia complex and developed cervical dystonia while taking risperidone therapy. We also review previously reported cases of dystonia in AIDS patients with the same causes and discuss the issue of increased vulnerability of the basal ganglia to HIV infection which, in turn, leads to increased sensitivity to neuroleptics. When dystonia is seen in AIDS patients, its pattern may be a clue to the ultimate cause. © 2003 Movement Disorder Society.",,"Factor, S. A.;Troche-Panetto, M.;Weaver, S. A.",2003,December,,0,
4460,Taking the pulse of aging: mapping pulse pressure and elasticity in cerebral arteries with optical methods,"Cerebrovascular support is crucial for healthy cognitive and brain aging. Arterial stiffening is a cause of reduced brain blood flow, a predictor of cognitive decline, and a risk factor for cerebrovascular accidents and Alzheimer's disease. Arterial health is influenced by lifestyle factors, such as cardiorespiratory fitness (CRF). We investigated new noninvasive optical measures of cerebrovascular health, which provide estimates of arterial pulse parameters (pulse pressure, transit time, and compliance/elasticity) within specific cerebral arteries and cortical regions, and low-resolution maps of large superficial cerebral arteries. We studied naturally occurring variability in these parameters in adults (aged 55-87), and found that these indices of cerebrovascular health are negatively correlated with age and positively with CRF and gray and white matter volumes. Further, regional pulse transit time predicts specific neuropsychological performance.","Aged;Aged, 80 and over;Aging/ physiology;Blood Pressure/ physiology;Cerebral Arteries/ physiology/physiopathology;Cerebrovascular Disorders/ diagnosis;Elasticity/ physiology;Female;Humans;Male;Middle Aged;Optical Imaging/ methods","Fabiani, M.;Low, K. A.;Tan, C. H.;Zimmerman, B.;Fletcher, M. A.;Schneider-Garces, N.;Maclin, E. L.;Chiarelli, A. M.;Sutton, B. P.;Gratton, G.",2014,Nov,10.1111/psyp.12288,0,
4461,Liver transplantion in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure,"Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.",,"Fabiani, G.;Rogacheski, E.;Wiederkehr, J. C.;Khouri, J.;Cianfarano, A.",2007,September,,0,
4462,The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI,"INTRODUCTION: While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. METHODS: Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. RESULTS: Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. CONCLUSIONS: Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population.",,"Ezzati, A.;Katz, M. J.;Lipton, M. L.;Lipton, R. B.;Verghese, J.",2015,Aug,10.1007/s00234-015-1536-2,0,
4463,Brain computed tomography of patients with HIV/AIDS before the advent of subsidized treatment program in Nigeria,"BACKGROUND: The objective is to study intracranial complications of HIV/AIDS using brain-computed tomography in patients who presented with neurological features before the advent of subsidized HIV/AIDS treatment program with highly active antiretroviral therapy (HAART) in Nigeria. MATERIALS AND METHODS: Retrospective study of patients' records retrieved from radiology and medical records departments of the hospital. The studied patients had HIV/AIDS and presented with neurological features and underwent CT scan. RESULTS: A total of 36 patients who tested positive for HIV and who presented with neurological features suspected to be complications of AIDS were examined with CT scan. They consisted of 24 male and 12 females. The male to female ratio was 2:1. The age of the patients ranged from 27 to 45 years. Seventeen patients (47.2%) were aged 30-34 years. Twenty-four patients (60%) were single while 12 (40%) were married. Twenty-seven patients (75%) were infected with HIV 1 and 2, five patients (13.9%) were infected only with HIV-1 while four were infected with only HIV-2. Presenting neurological complaints include left hemiplegia 13 (36.1%), right hemiplegia 6 (16.7%), coma 7 (19.4%), memory loss/dementia complex 5 (13.9%), convulsion with coma 2 (5.6%), left hemi-pariesis with memory loss 2 (5.6%), and staggering gait 1 (2.8%). The findings in CT scan include infarcts-like lesions 14 (38.9%), multiple ring-enhancing lesions 7 (19.4%), cerebral atrophy 5 (13.9%), multiple nodular lesions 4 (11.1%), acute intracerebral hemorrhage 3 (8.3%), cerebral hemiatrophy 2 (5.6%), and solitary ring-enhancing lesions 1 (2.8%). Eight patients with single or multiple ring enhancing lesions were treated with empirical treatment for toxoplasmosis but only three (37.5%) made full recovery. CONCLUSION: Brain CT scan showed extensive structural damages in patients with HIV/AIDS who were not treated with HAART. Out-of-pocket payment for investigations and treatment and absence of HAART could be partly responsible for high rate of advanced disease.",Brain-computed tomography;Hiv/aids;Nigeria;neurological features;poverty,"Eze, K. C.;Eze, E. U.",2012,Oct,10.4103/0300-1652.107601,0,
4464,"Dysglycemia, brain volume and vascular lesions on MRI in a memory clinic population","Objective It is unclear, if the association between abnormalities in glucose metabolism (dysglycemia) and impaired cognitive functioning is primarily driven by degenerative or vascular brain damage. We therefore examined the relation between dysglycemia and brain volume and vascular lesions on MRI in a memory clinic population. Methods The relations between markers of glycemia (HbA1c and fasting glucose levels) and normalized brain volume, medial temporal lobe atrophy and vascular lesions (white matter hyperintensities, lacunes) were assessed in 274 consecutive patients attending a memory clinic, using linear regression analyses. Results Clinical diagnoses were subjective complaints (n = 117), mild cognitive impairment (n = 62), Alzheimer's disease (n = 61) and other type of dementia (n = 34). Twenty patients had a history of diabetes. Across the whole study population there was no relation between HbA1c or fasting glucose and the brain MRI measurements, after adjustments for age, sex and diagnostic group. Secondary analyses after stratification by diabetes status, diagnosis and median age (67 years) did not change the results. Conclusion In this memory clinic population, dysglycemia was not associated with either brain volume or vascular lesions. Apparently, dysglycemia is not associated with a specific class of brain pathology in patients with cognitive complaints. © 2014 Elsevier Inc.",glucose;hemoglobin A1c;adult;aged;Alzheimer disease;article;brain atrophy;brain size;dementia;diabetes mellitus;diagnosis related group;dysglycemia;female;glucose blood level;hemoglobin blood level;human;major clinical study;male;middle aged;mild cognitive impairment;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;temporal lobe;vascular lesion;Magnetom Impact Expert scanner,"Exalto, L. G.;Van Der Flier, W. M.;Scheltens, P.;Vrenken, H.;Biessels, G. J.",2014,,,0,
4465,Multicenter assessment of reliability of cranial MRI,"Clinical utility of magnetic resonance imaging (MRI) for the diagnosis and assessment of neurodegenerative diseases may depend upon the reliability of MRI measurements, especially when applied within a multicenter context. In the present study, we assessed the reliability of MRI through a phantom test at a total of eleven clinics. Performance and entry criteria were defined liberally in order to support generalizability of the results. For manual hippocampal volumetry, automatic segmentation of brain compartments and voxel-based morphometry, multicenter variability was assessed on the basis of MRIs of a single subject scanned at ten of the eleven sites. In addition, cranial MRI scans obtained from 73 patients with Alzheimer's disease (AD) and 76 patients with mild cognitive impairment were collected at subset of six centers to assess differences in grey matter volume. Results show that nine out of eleven centers tested met the reliability criteria of the phantom test, where two centers showed aberrations in spatial resolution, slice thickness and slice position. The coefficient of variation was 3.55% for hippocampus volumetry, 5.02% for grey matter, 4.87% for white matter and 4.66% for cerebrospinal fluid (CSF). The coefficient of variation was 12.81% (S.D. = 9.06) for the voxel intensities within grey matter and 8.19% (S.D. = 6.9) within white matter. Power analysis for the detection of a difference in the volumes of grey matter between AD and MCI patients across centers (d = 0.42) showed that the total sample size needed is N = 180. In conclusion, despite minimal inclusion criteria, the reliability of MRI across centers was relatively good. © 2005 Elsevier Inc. All rights reserved.",,"Ewers, M.;Teipel, S. J.;Dietrich, O.;Schönberg, S. O.;Jessen, F.;Heun, R.;Scheltens, P.;Pol, L. v d;Freymann, N. R.;Moeller, H. J.;Hampel, H.",2006,August,,0,
4466,Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease,"The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer's disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.","Aged;Aged, 80 and over;Alzheimer Disease/*cerebrospinal fluid/*pathology;Amyloid Precursor Protein Secretases/*cerebrospinal fluid;Amyloid beta-Peptides/cerebrospinal fluid;Aspartic Acid Endopeptidases/*cerebrospinal fluid;Female;Functional Laterality;Hippocampus/*pathology;Humans;Linear Models;Magnetic Resonance Imaging;Male;Peptide Fragments/cerebrospinal fluid;tau Proteins/cerebrospinal fluid","Ewers, M.;Cheng, X.;Zhong, Z.;Nural, H. F.;Walsh, C.;Meindl, T.;Teipel, S. J.;Buerger, K.;He, P.;Shen, Y.;Hampel, H.",2011,,10.3233/jad-2011-091153,0,
4467,Anatomical-functional correlation using an adjustable MRI-based region of interest atlas with positron emission tomography,"A procedure is described for combining anatomical information from magnetic resonance imaging (MRI) or computerized tomography (CT) and functional information from positron emission tomography (PET) in a rapid fashion. MRI data are combined with a procedure for the definition, storage, and recall of anatomically based regions of interest. An atlas of standard regions of interest, defined for a set of 18 parallel planes spaced at 6-mm intervals, provides an initial region of interest template for each patient slice. Global adjustments to scale, orientation, and position are applied to obtain an initial match. Individual regions of interest may then be moved, deleted, or redrawn as needed. The ability to store region of interest templates ensures reproducibility of analysis over long periods and introduces a standardization of analysis technique. In 25 brain structures, the mean coefficient of variation in cerebral glucose utilization rate (CMRGlc) measurements among five neuroanatomically trained observers was reduced from 8.1% for manual region of interest definition to 4.0% using the template approach with MRI. Template analysis for space-occupying lesions such as tumors or infarcts is illustrated with PET data from a stroke study, emphasizing the facility for rapid, reproducible analysis of multifunctional studies. MRI-PET matching for a structurally intact caudate nucleus having reduced CMRGlc in Huntington's disease emphasizes the accuracy of anatomical localization required to quantify small structures.",,"Evans, A. C.;Beil, C.;Marrett, S.;Thompson, C. J.;Hakim, A.",1988,1988,,0,
4468,"Computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia. A prospective clinicopathologic study","The accuracy of computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia was studied prospectively. Out of 50 demented patients, autopsy revealed 32 cases with either senile dementia of the Alzheimer's type (SDAT), multi-infarct dementia (MID), or a combination of both. Eighteen patients had dementia caused by other diseases. Based on a combination of computed tomography, electroencephalography, and clinical features, senile dementia of the Alzheimer's type was differentiated from all 50 patients, with a specificity of 83% and a sensitivity of 80%. Focusing on senile dementia of the Alzheimer's type, multi-infarct dementia, or a combination of both, specificity decreased to 65% and sensitivity to 47%. Comparing the different methods, multi-infarct processes were diagnosed with a higher sensitivity by the clinical features (73%) than by computed tomography (18%) or electroencephalography (18%). None of the methods validly differentiated multi-infarct dementia from a combination of multi-infarct dementia and senile dementia of the Alzheimer's type.",adult;aged;Alzheimer disease;clinical article;computer analysis;computer assisted tomography;dementia;electroencephalography;female;human;male;methodology;multiinfarct dementia;priority journal,"Ettlin, T. M.;Staehelin, H. B.;Kischka, U.;Ulrich, J.;Scollo-Lavizzari, G.;Wiggli, U.;Seiler, W. O.",1989,,,0,
4469,Anterior temporal lobe involvement: Useful magnetic resonance imaging sign to diagnose Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy,,,"Eswaradass, P. V.;Ramasamy, B.;Kalidoss, R.;Gnanashanmugham, G.",2015,1,,0,
4470,Sclerosing vasculopathy of the central nervous system in nonelderly demented patients,"Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging.",,"Estes, M. L.;Chimowitz, M. I.;Awad, I. A.;McMahon, J. T.;Furlan, A. J.;Ratliff, N. B.",1991,1991,,0,
4471,Increased cortical capillary transit time heterogeneity in Alzheimer's disease: a DSC-MRI perfusion study,"Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and neurotoxic Abeta in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study, we compared cerebral microcirculation in a cohort of AD and mild cognitive impairment (MCI) patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than 2 years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared with controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal, and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.",Alzheimer;Capillary transit-time heterogeneity (CTH);Mri;Oxygen extraction fraction (OEF);Perfusion;White matter hyperintensities,"Eskildsen, S. F.;Gyldensted, L.;Nagenthiraja, K.;Nielsen, R. B.;Hansen, M. B.;Dalby, R. B.;Frandsen, J.;Rodell, A.;Gyldensted, C.;Jespersen, S. N.;Lund, T. E.;Mouridsen, K.;Braendgaard, H.;Ostergaard, L.",2017,Feb,,0,
4472,Vascular smooth muscle actin is reduced in Alzheimer disease brain: a quantitative analysis,"We analyzed smooth muscle actin (SMA) immunoreactivity in brain blood vessels of 10 ApoE 4,4 Alzheimer disease (AD) patients and 10 ApoE 3,3 AD patients matched for age, sex, and duration of dementia. We also examined 10 cognitively and neuropathologically normal controls matched for age and sex. Vascular SMA immunoreactivity in the arachnoid, grey matter, and white matter was quantified by image analysis. There was less SMA immunoreactivity in blood vessels of all AD patients when compared to cognitively and neuropathologically normal controls (p < 0.001). In addition, arachnoidal vessels of ApoE 4,4 AD patients had less SMA immunoreactivity than ApoE 3,3 AD patients (p < 0.05). There is decreased vascular SMA density in arachnoid, grey matter, and white matter blood vessels in patients with AD when compared to age matched, cognitively and neuropathologically normal controls. The severity of the loss of SMA within the AD group may depend on ApoE type.","Actins/deficiency/ metabolism;Aged;Aged, 80 and over;Alzheimer Disease/ metabolism/pathology/physiopathology;Apolipoprotein E3;Apolipoprotein E4;Apolipoproteins E/genetics;Arachnoid/blood supply/pathology/physiopathology;Brain/ blood supply/pathology/physiopathology;Cerebral Arteries/ metabolism/pathology/physiopathology;Down-Regulation/physiology;Female;Genotype;Humans;Image Processing, Computer-Assisted;Immunohistochemistry;Male;Middle Aged;Muscle, Smooth, Vascular/ metabolism/pathology/physiopathology;Nerve Fibers, Myelinated/metabolism/pathology;Reference Values","Ervin, J. F.;Pannell, C.;Szymanski, M.;Welsh-Bohmer, K.;Schmechel, D. E.;Hulette, C. M.",2004,Jul,,0,
4473,Neuropathologic basis of white matter hyperintensity accumulation with advanced age,"OBJECTIVE: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. METHODS: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1. RESULTS: Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). CONCLUSION: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.","Aged, 80 and over;Aging/*pathology;Alzheimer Disease/*pathology;Apolipoproteins E/genetics;Autopsy;Brain/*pathology;Cerebrovascular Disorders/*pathology;Chi-Square Distribution;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Neurofibrillary Tangles/pathology;Retrospective Studies","Erten-Lyons, D.;Woltjer, R.;Kaye, J.;Mattek, N.;Dodge, H. H.;Green, S.;Tran, H.;Howieson, D. B.;Wild, K.;Silbert, L. C.",2013,Sep 10,10.1212/WNL.0b013e3182a43e45,0,
4474,Neuropathologic basis of age-associated brain atrophy,"Importance: While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy. Objective: To examine the association between brain atrophy during life and neuropathology in an elderly population. Design: Autopsy study of a cohort of elderly individuals. Setting: Community-based population. Participants: Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death. Main Outcomes and Measures: The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death. Results: Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy. Conclusions and Relevance: Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment. ©2013 American Medical Association. All rights reserved.",,"Erten-Lyons, D.;Dodge, H. H.;Woltjer, R.;Silbert, L. C.;Howieson, D. B.;Kramer, P.;Kaye, J. A.",2013,May,,0,
4475,Are granular osmiophilic material deposits an epiphenomenon in CADASIL?,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Pathophysiologically, there seems to be multimerization of the extracellular domain of the protein with a possible gain of function on vascular smooth muscular cells. However, the mechanisms and determinants of NOTCH3 multimerization are not completely understood, and it is not completely elucidated whether NOTCH3 multimerization contributes to the appearance of granular osmiophilic material (GOM) deposits, which are the pathological hallmark of CADASIL. We recently reported a patient with parkinsonism and cognitive impairment and with evidence of diffuse white matter changes on imaging, carrying a NOTCH3 nonsense mutation in exon 3 (c.307C>T), and suggested that such a hypomorphic NOTCH3 mutation was likely to be pathogenic. We further pursued ultrastructural examination of skin vessels in our case, and here we report the results, wishing to make a comment on whether GOM deposits should be considered the pathological hallmark for a definitive diagnosis of CADASIL in those patients whose mutations are predicted in the production of hypomorphic protein products.",,"Erro, R.;Moccia, M.;Cervasio, M.;Penco, S.;Del Basso De Caro, M.;Barone, P.",2015,2015,,0,
4476,"Progressive parkinsonism, balance difficulties, and supranuclear gaze palsy","A 76-year-old man presented with a 4-year history of a progressive parkinsonian syndrome. It started with slowness of gait and mood dysfunction. Symptoms slowly progressed and further included occasional unexplained falls. On examination, he showed a severe parkinsonian syndrome featuring bradykinesia, rigidity (axial > appendicular), and positive pull-test finding. Moreover, there was an upgaze supranuclear palsy and slow saccades on vertical plane. Magnetic resonance imaging was performed that revealed significant basal ganglia lesions and white matter hyperintensities, including periventricular regions and both frontal and temporal subcortical areas, along with moderate widespread atrophy and ventricular enlargement. Here, we reveal the pathological diagnosis and discuss the approach to the clinical data. Copyright 2014 American Medical Association. All rights reserved.",,"Erro, R.;Lees, A. J.;Moccia, M.;Picillo, M.;Penco, S.;Mosca, L.;Vitale, C.;Barone, P.",2014,January,,0,
4477,"Anesthetic management of a patient diagnosed with CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy)","CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leu-koencephalopathy) is an infrequent inherited disease that could have anesthetic implica-tions. However these have rarely been reported. We present a male patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, and sustained dementia, mood alterations, apathy, and urine incontinence. He had famil-ial antecedents of psychiatric symptoms and ischemic stroke events in several relatives including his father, two brothers and one sister. He was scheduled for arthrodesis of the left knee because of multiple infectious complications of prosthetic knee surgery. He was under clopidogrel treatment which was withdrawn seven days before surgery. The pro-cedure was performed under combined spinal-epidural anesthesia, intraoperative seda-tion with midazolam, and postoperative multimodal analgesia including epidural patient controlled analgesia. The perioperative management was uneventful and we outline the adequacy of managing these patients under regional anesthesia and analgesia, as these permit to maintain hemodynamic stability leading to adequate cerebral perfusion, key to avoid an increase in the effects of the chronic arteriopathy patients with CADASIL sustain.",adverse effects;arthrodesis;CADASIL;case report;complication;epidural anesthesia;human;knee prosthesis;male;middle aged;infection;spinal anesthesia,"Errando, C. L.;Navarro, L.;Vila, M.;Pallardó, M. A.",2012,,,0,
4478,Lower brain glutamate is associated with cognitive deficits in HIV patients: A new mechanism for HIV-associated neurocognitive disorder,"Purpose To determine whether subjects with human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) show altered concentrations of brain glutamate (GLU), and whether lower GLU levels correlate with cognitive deficits. Materials and Methods GLU concentrations were measured in the basal ganglia, frontal gray and white matter, and parietal gray matter of 45 HIV-positive and 46 age-and-education-matched HIV-negative subjects using echo-time averaged proton magnetic resonance spectroscopy (1H MRS). Results Compared to controls, HIV subjects with cognitive deficits had lower GLU in the parietal gray matter, while those without cognitive deficits tended to show higher basal ganglia GLU. Lower parietal and frontal gray matter GLU were associated with a greater number of nucleoside reverse transcriptase inhibitors, and were predictive of poorer cognitive performance. Correlations between GLU and cognitive performance, but not the other findings, remained significant after correction for multiple comparisons. Conclusion Parietal gray matter GLU is lower in HIV subjects with cognitive deficits. This reduction might result from reduced astrocytic reuptake of GLU, secondary excitotoxicity, and mitochondrial toxicity from antiretroviral treatments. The glutamatergic system may play an important role in the pathophysiology of HAND, and brain GLU on 1H MRS may provide an early surrogate marker for monitoring disease severity and treatment effects. © 2010 Wiley-Liss, Inc.",glutamic acid;RNA directed DNA polymerase inhibitor;adult;age;amino acid brain level;article;basal ganglion;clinical article;cognitive defect;controlled study;disease duration;educational status;female;gray matter;HIV associated dementia;human;Human immunodeficiency virus infected patient;Karnofsky Performance Status;male;neuropsychology;priority journal;sex difference;virus load;white matter,"Ernst, T.;Jiang, C. S.;Nakama, H.;Buchthal, S.;Chang, L.",2010,,,0,
4479,Changes in cerebral metabolism are detected prior to perfusion changes in early HIV-CMC: A coregistered (1)H MRS and SPECT study,"Human immunodeficiency virus-cognitive motor complex (HIV-CMC), a common complication of the acquired immunodeficiency syndrome (AIDS), is characterized by progressive cognitive impairment and motor dysfunction. Functional imaging methods, such as single-photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), have been applied to assess the severity of brain injury. However, it is unclear which of these two methods is more sensitive in detecting brain abnormalities in patients with early HIV-CMC. Twenty-four HIV-CMC patients were compared with 34 healthy subjects; each had quantitative SPECT ((133)Xenon-calibrated (99m)Tc-HMPAO) and quantitative (1)H-MRS. Both modalities were co-registered in order to assess regional cerebral blood flow (rCBF) and metabolite concentrations within the same voxel of interest in four brain regions (midfrontal and midparietal gray matter, temporoparietal white matter, and basal ganglia). On SPECT, only the temporoparietal white matter showed a trend for decreased rCBF in HIV-CMC patients (-13%, P = 0.06). On MRS, HIV-CMC patients showed significantly reduced creatine concentration in the basal ganglia (-8%, P = 0.008), as well as increased myoinositol concentrations in the basal ganglia (+25%, P = 0.01) and the temporoparietal white matter (+18%, P = 0.08). There was no significant correlation between SPECT and MRS variables in the patients in any region. (1)H MRS showed abnormal neurochemistry in the basal ganglia, whereas rCBF on SPECT was normal in the same region. This finding suggests that metabolite concentrations on (1)H MRS are better surrogate markers than rCBF measurements with SPECT for the evaluation of brain injury in early HIV-CMC. J. Magn. Reson. Imaging 2000;12:859-865.","AIDS Dementia Complex/ diagnosis/physiopathology;Adult;Basal Ganglia/pathology/physiopathology;Brain/pathology/physiopathology;Brain Ischemia/ diagnosis/physiopathology;Brain Mapping;Cerebral Cortex/pathology/physiopathology;Cerebrovascular Circulation/physiology;Energy Metabolism/ physiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Reference Values;Regional Blood Flow/physiology;Tomography, Emission-Computed, Single-Photon","Ernst, T.;Itti, E.;Itti, L.;Chang, L.",2000,Dec,,0,
4480,Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging,"PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.","AIDS Dementia Complex/ pathology;Adult;Brain/ pathology;Diagnosis, Differential;Humans;Image Processing, Computer-Assisted;Leukoencephalopathy, Progressive Multifocal/ pathology;Magnetic Resonance Imaging/ methods;Middle Aged;Prospective Studies","Ernst, T.;Chang, L.;Witt, M.;Walot, I.;Aronow, H.;Leonido-Yee, M.;Singer, E.",1999,Feb,10.1148/radiology.210.2.r99fe19539,0,
4481,Increased glial metabolites predict increased working memory network activation in HIV brain injury,"Deficits in attention and working memory are common in human immuno deficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy (1H MRS) and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. To evaluate the model that attentional deficits in early HIV brain disease are related to brain inflammation, 1H MRS and fMRI were performed in 14 HIV-positive subjects [acquired immunodeficiency syndrome (AIDS) dementia complex stage 1 or less]. Increasing attentional load on three working memory tasks was assessed with fMRI, and the concentrations of brain metabolites were measured with 1H MRS in the frontal gray and white matter, and basal ganglia. Metabolite concentrations were correlated with fMRI blood oxygenation level-dependent (BOLD) signals, using a random-effects linear regression model in SPM99. Several positive correlations were observed between the BOLD signal strength in the working memory network (posterior parietal cortex and lateral prefrontal cortex) and the concentrations of frontal white matter and basal ganglia metabolites that are predominant in glial cells (choline-containing compounds, myo-inositol, and total creatine). In contrast, BOLD signals in the working memory network were not correlated with the concentration of N-acetyl compounds, which are markers of neuronal viability, or with metabolite concentrations in the frontal gray matter. These findings are consistent with previous results that mild HIV brain injury is associated with increased glial activation without major involvement of neuronal abnormalities. We propose that the inflammatory glial abnormalities reduce the efficiency of neural processing, and necessitate compensatory increases in attention in patients, and associated BOLD signals, to perform a given task. The same mechanism may also contribute to cognitive dysfunction in other brain diseases that involve inflammation. © 2003 Elsevier Science (USA). All rights reserved.",acetic acid derivative;biochemical marker;choline derivative;creatinine;inositol;adult;article;basal ganglion;blood oxygenation;brain function;brain metabolism;cell viability;clinical article;controlled study;correlation analysis;frontal cortex;glia cell;gray matter;human;Human immunodeficiency virus infection;image analysis;male;nuclear magnetic resonance imaging;parietal lobe;prediction;prefrontal cortex;proton nuclear magnetic resonance;randomization;white matter;working memory,"Ernst, T.;Chang, L.;Arnold, S.",2003,,,0,
4482,"Nuclear magnetic resonance imaging in dementias, preliminary results","We studied thirteen typical cases of different types of dementia. The diagnosis of dementia and its differential diagnosis were based on criteria reported elsewhere, using a broad clinical examination. The patients were 6 men and 7 women, age 55 - 75 years. Four patients had primary degenerative dementia (3 Alzheimer disease, 1 Pick's disease) and nine had vascular dementia (3 multiple stroke type, 3 lacunar state type, 3 Binswanger's type). In the primary degenerative dementia (Alzheimer's and Pick's disease) the CT scans showed mild to moderate central and cortical atrophy with no parenchymal changes. The T1- and T2-weighted NMR images showed similar atrophy without any other abnormalities. In the multiple stroke type of vascular dementia multiple cortical and subcortical hypodense lesions on the CT scans were compatible with old infarcts. All patients had bilateral lesions. Localized hypodense areas around the frontal and occipital horns were seen. The NMR findings were similar to the CT findings, although the T2-weighted image showed better contrast. In the lacunar state type of vascular dementia the CT scans showed moderate central atrophy and mild to moderate cortical atrophy in the temporal and parietal areas. There was moderate to severe decreased density in the white matter of the whole paraventricular area. Lacunar infarcts were located in the thalamus of two patients, and in one patient there was an infarct frontally. The NMR findings were similar to the CT findings, although the T2-weighted image gave better contrast. In the Binswanger's type of vascular dementia the CT scans revealed moderate central and mild to moderate cortical atrophy. There were large hypodense areas bilaterally in the white matter. Similar changes were visible with NMR, but the white matter changes were more clearly seen in the T2-weighted image.",adult;aged;Alzheimer disease;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;great blood vessel;human;nuclear magnetic resonance imaging;Pick presenile dementia;psychological aspect,"Erkinjuntti, T.;Sipponen, J. T.;Iivanainen, M.",1984,,,0,
4483,Cerebral NMR and CT imaging in dementia,"Thirteen patients with different types of dementia were studied with nuclear magnetic resonance (NMR) and CT imaging of the brain. The overall correlation between CT and NMR findings was good. Areas of hypodensity in cerebral white matter on CT were especially well visualized in the T2-weighted NMR images. Hypodense areas were seen in the white matter of patients with vascular dementias but not in those with primary degenerative dementias. Thus, the presence or absence of white matter changes may be an important factor in the differential diagnosis of vascular dementia and primary degenerative dementia. On the basis of NMR and CT findings, it was difficult to distinguish between the lacunar state type and Binswanger type of vascular dementia. It is suggested, therefore, that these two subgroups of vascular dementia be commonly named angiopathic dementia.",,"Erkinjuntti, T.;Sipponen, J. T.;Iivanainen, M.",1984,1984,,0,
4484,EEG in the differential diagnosis between Alzheimer's disease and vascular dementia,"Demented patients with Alzheimer's disease (AD) (n = 67), multi-infarct dementia (MID) (n = 77) and probable vascular dementia (PVD) (n = 45) were studied with electroencephalography (EEG). All patients underwent a routine EEG examination and quantitative EEG was recorded from 14 patients with AD, 20 with MID, and 12 with PVD. The patient groups did not differ in regard to sex, age, education, or degree of dementia. Diffuse abnormality of EEG increased in AD, while driving response to photic stimulation and the mean frequency of background activity decreased in all groups with increasing degree of dementia. In quantitative EEG, the percentage of alpha power decreased and those of theta and delta power increased relative to the degree of dementia. Focal abnormalities, and irritative (spikes and/or sharp waves) and slow wave paroxysms were more common in MID than in AD. Patients with different types of dementia did not differ significantly in regard to diffuse abnormality, occurrence of driving response, mean background frequency, or parameters of quantitative EEG. The mean frequency of background activity and the degree of diffuse abnormality correlated with central and cortical atrophy, white matter low attenuation seen on computed tomography, and with neuropsychological findings.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/physiopathology;Brain/physiopathology/radiography;Dementia/*diagnosis/physiopathology;Diagnosis, Differential;*Electroencephalography;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Tomography, X-Ray Computed","Erkinjuntti, T.;Larsen, T.;Sulkava, R.;Ketonen, L.;Laaksonen, R.;Palo, J.",1988,Jan,,0,
4485,CT in the differential diagnosis between Alzheimer's disease and vascular dementia,"A prospective series of consecutively admitted patients with Alzheimer's disease (AD) (n = 68), multi-infarct dementia (MID) (n = 79) and probable vascular dementia (PVD) (n = 46) were studied by CT of the head. In MID 88.6% and in PVD 41.3% of the patients had at least one brain infarct on CT, but only one patient (1.5%) with AD. White matter low attenuation (WMLA) also differentiated MID and PVD from AD, especially among patients aged 75 years or less, and with mild or moderate dementia. In all types, brain atrophy on CT had a positive correlation with the degree of dementia. Infarcts and WMLA on CT, but not brain atrophy seem to be of differential diagnostic value between vascular and degenerative dementia.","Aged;Alzheimer Disease/*radiography;Brain/*radiography;Dementia/*radiography;Diagnosis, Differential;Female;Humans;Male;Prospective Studies;*Tomography, X-Ray Computed","Erkinjuntti, T.;Ketonen, L.;Sulkava, R.;Vuorialho, M.;Palo, J.",1987,Apr,,0,
4486,Limitations of clinical criteria for the diagnosis of vascular dementia in clinical trials. Is a focus on subcortical vascular dementia a solution?,"Vascular dementia (VaD) includes several different vascular mechanisms and changes in the brain, and has different causes and clinical manifestations. Critical to its conceptualization and diagnosis are definitions of the cognitive syndrome, vascular etiologies, and changes in the brain. Variation in these has resulted in different definitions of VaD, estimates of prevalence, and types and distribution of brain lesions. This definitional heterogeneity may have been a factor for negative results in prior clinical trials on VaD. We propose that the division of VaD into subtypes can identify a more homogeneous group of patients for drug trials. A so-called ""subcortical"" VaD could incorporate two old clinical entities ""Binswanger's disease"" and ""the lacunar state."" Small vessel disease is the primary vascular etiology, lacunar infarcts and ischemic white matter lesions are the primary type of brain lesions, the subcortical areas and frontal connections are the primary location of lesions, and a subcortical syndrome as the primary clinical manifestation. The clinical syndromes are likely more variable, and urgently need to be categorized. Selection of these patients for clinical trials could mainly be based on brain imaging features, where the essential changes and the main aspects of the lesions include extensive ischemic white matter lesions and lacunar infarcts in the deep gray and white matter structures. Subcortical VaD is expected to show a more predictable clinical picture, natural history, outcomes, and treatment responses.","Brain/blood supply/pathology;Cerebrovascular Circulation;Clinical Trials as Topic;Cognition;Dementia, Vascular/ classification/ diagnosis/physiopathology/psychology;Diagnosis, Differential;Humans","Erkinjuntti, T.;Inzitari, D.;Pantoni, L.;Wallin, A.;Scheltens, P.;Rockwood, K.;Desmond, D. W.",2000,Apr,,0,
4487,Lack of difference in brain hyperintensities between patients with early Alzheimer's disease and control subjects,"Objective: To rate magnetic resonance image signal hyperintensities in clearly defined white and deep gray matter areas in patients with early Alzheimer's disease and controls. Design: Prospective series. The National Institute for Neurological Disorders and Stroke-The Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease. Blinded assessment. Setting: University hospital, dementia study group. Subjects: Thirty-four patients with Alzheimer's disease. Thirty-eight age- matched healthy community volunteers. Measures: Frequency of hyperintensities in axial magnetic resonance images (1.5-T system) seen both in the proton density and T(2)-weighted scans examined in vascular centrencephalon, centrum semiovale, watershed, periventricular, and subcortical white matter. Periventricular hyperintensities classification include caps, thin lining, and smooth and irregular halo. Hyperintensities in other areas include small and large focal, focal confluent, and diffusely confluent. The hyperintensities were counted and rated using a five-point scale and the Fazekas method. Results: No difference in the ratings, frequency, or extent of the hyperintensities between patients with early Alzheimer's disease and controls. Majority of patients and controls had two or fewer hyperintensities and they were mostly small foci, caps, and thin linings. The hyperintensities are associated with arterial hypertension, diabetes, cardiac disorder, and age in different combinations, but not with Alzheimer's disease. Conclusion: Tiny hyperintensities on magnetic resonance images are frequent both in patients with early Alzheimer's disease and in healthy controls; most of the lesions are not related to brain ischemia. When age and vascular risk factors were taken into account, no difference between patients with early Alzheimer's disease and control subjects could be detected.",,"Erkinjuntti, T.;Gao, F.;Lee, D. H.;Eliasziw, M.;Mershey, H.;Hachinski, V. C.",1994,1994,,0,
4488,Subcortical ischemic vascular disease and dementia,"Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischemic white-matter lesions (WMLs) as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities: Binswanger's syndrome and the lacunar state. Patients with SIVD present with extensive white-matter lesions and multiple lacunae on neuroimaging. SIVD is expected to be a more homogenous subtype of vascular cognitive impairment and dementia. Recently modified NINDS-AIREN research criteria for SIVD have been proposed. Further empirical research is needed to refine the syndrome and stages and validate the brain imaging criteria, as well as to detail the natural history and outcomes of SIVD.",Aged;Brain Ischemia/ complications;Cognition Disorders/ etiology;Dementia/ etiology;Humans,"Erkinjuntti, T.",2003,,10.1017/s1041610203008925,0,
4489,Types of multi-infarct dementia,"A series of 79 patients with multi-infarct dementia (MID) were divided into 2 groups designated cortical MID and subcortical MID, according to whether the computed tomography (CT) scan showed the presence or absence of cortical infarcts, and an absent to mild or moderate to severe degree of white matter low attenuation (WMLA). Cortical MID was characterized by repeated atherothrombotic and cardiogenic strokes, moto-sensory hemiparesis, a severer degree of aphasia, and abrupt onset of cognitive failure. Subcortical MID typically showed the following features: lacunar strokes, bulbar signs including dysarthria, pure motor hemiparesis, depression and emotional lability. WMLA was found in all patients with subcortical MID but also in over 60% of those with cortical MID. In the 2 groups CT scans showed equal frequencies of deep infarcts. When divided according to severity of WMLA, 92% of patients in the cortical MID group and 44% of those in the subcortical MID group were found to have at least one cortical infarct on the CT scan. Although cortical and subcortical MID differed in several clinical features, they did not show major differences in the risk factors for stroke, and clearly overlapped each other as regards ischaemic scores and the findings in neurological examinations and CT. Thus, it is still an open question whether cortical MID and subcortical MID, including the lacunar state and Binswanger's disease, are 2 distinct entities or merely represent the expression of biological variation while having the same etiopathogenesis.",brain infarction;central nervous system;computer assisted tomography;diagnosis;dysarthria;human;major clinical study;multiinfarct dementia;priority journal,"Erkinjuntti, T.",1987,,,0,
4490,Differential diagnosis between Alzheimer's disease and vascular dementia: evaluation of common clinical methods,"A prospective series of consecutively admitted demented patients were examined in order to evaluate the role of common clinical methods in the differential diagnosis between Alzheimer's disease (AD) and vascular dementia. Patients fulfilling the DSM-III criteria for vascular dementia were divided into multi-infarct dementia (MID) and probable vascular dementia (PVD), the latter including also cases with combined vascular and degenerative dementia. The series consisted of 68 patients with AD, 79 with MID and 46 with PVD. These groups did not differ in regard to sex, age or degree of dementia. Absence of cardio- and cerebrovascular diseases differentiated AD from MID and PVD. Also absence of corticospinal tract signs and gait disorders differentiated AD from MID and PVD and that of bulbar signs AD from MID. Infarcts and white matter low attenuation on CT differentiated MID and PVD from AD. Altogether 88.6% of the MID patients and 41.3% with PVD had brain infarct on CT, but only one with AD. Ischemic scores seemed also to be useful in the differential diagnosis between AD and vascular dementia. Quantitative neuropsychology, EEG, routine cerebrospinal fluid and other laboratory investigations, including serum glucose and plasma lipids, seem to be less valuable.",Alzheimer disease;central nervous system;cerebrovascular disease;clinical feature;computer analysis;computer assisted tomography;diagnosis;differential diagnosis;electrocardiography;electroencephalography;female;human;major clinical study;male;methodology;multiinfarct dementia;psychological aspect;psychology,"Erkinjuntti, T.",1987,,,0,
4491,Binswanger disease. A blood pressure-related dementia,"Interest in Binswanger's disease has increased during the past decade, owing to the possibility of detecting white matter changes with computerised and magnetic resonance tomography. This paper consists in a summary of clinical symptoms and signs and possible diagnostic criteria, discussion of differential diagnosis, and the presentation of two own cases. Both patients manifested mild dementia and gait disturbance, and one had frequent drop attacks. Severe supra- and infra-tentorial white matter changes were present in both cases. It is important to consider a possible diagnosis of Binswanger's disease, as treatment of the appropriate risk factors may prevent or delay the development of dementia.",aged;article;brain;case report;computer assisted tomography;differential diagnosis;female;human;multiinfarct dementia;nuclear magnetic resonance imaging;pathology;pathophysiology;radiography;syndrome,"Eriksson, S. E.;Johansson, I.;Lind, B.;Olsson, J. E.",1994,,,0,
4492,Verbal memory impairment in subcortical ischemic vascular disease. A descriptive analysis in CADASIL,"In the elderly, the high prevalence of Alzheimer's disease neuropathology presents a major challenge to the investigation of memory decline in common diseases such as small vessel disease. CADASIL represents a unique clinical model to determine the spectrum of memory impairment in subcortical ischemic vascular dementia (SIVD). One hundred and forty CADASIL patients underwent detailed clinical, neuropsychological and imaging analyses. The Free and Cued Selective Reminding Test was used as a measure of verbal memory. Forty-four out of 140 CADASIL patients (31.4%) presented with memory impairment according to this test. Eight out of 44 (18.2%) subjects with memory impairment matched the definition of the amnestic syndrome of hippocampal type. While alterations in spontaneous recall were related to the severity of subcortical ischemic lesions, the profile of memory impairment, particularly the sensitivity to cueing was found related to other factors such as hippocampal atrophy. © 2010 Elsevier Inc.",,"Epelbaum, S.;Benisty, S.;Reyes, S.;O'Sullivan, M.;Jouvent, E.;Düring, M.;Hervé, D.;Opherk, C.;Hernandez, K.;Kurtz, A.;Viswanathan, A.;Bousser, M. G.;Dichgans, M.;Chabriat, H.",2011,December,,0,
4493,Progression of cerebral white matter lesions - Clinical and radiological considerations,"More than half of all elderly have some degree of white matter lesions (WML) on MRI of the brain. Until recently, the rate of progression of WML was unknown. Recent work within several population based large scale studies was devoted to tackle this question, to identify factors related to WML progression and to establish a relationship with clinical variables and cognitive changes. There is converging evidence that at least a subset of WML demonstrates considerable progression over time. Increases in WML volume have been correlated with increased loss of brain volume and decline in cognitive and motor performance, indicating that progression of WML harbors clinical relevance. Correlative MRI-histopathologic studies and the clustering of vascular risk factors in subjects with progressive WML support a vascular aetiology of WML, particularly in ""confluent"" MRI phenotypes. Although specific rating scales have been proposed to detect WML progression, quantitative measurements appear superior given their objective and reproducible nature and regarding possibilities of statistical analyses. Measuring changes in the progression of WML may provide a valid surrogate marker in future clinical trials on cerebral small-vessel disease. Power calculations based on quantitative data of the Austrian Stroke Prevention Study (ASPS) suggest that such studies would be feasible. © 2007 Elsevier B.V. All rights reserved.",aging;article;brain atrophy;brain damage;brain size;calculation;cognitive defect;correlation analysis;diagnostic imaging;disease course;disease marker;histopathology;human;image analysis;measurement;motor dysfunction;motor performance;neuroimaging;nuclear magnetic resonance imaging;phenotype;population research;priority journal;reproducibility;risk factor;white matter;white matter lesion,"Enzinger, C.;Fazekas, F.;Ropele, S.;Schmidt, R.",2007,,,0,
4494,Factors associated with progression of brain atrophy during ageing: 6 year follow-up from the Austrian stroke prevention study,"Neuroimaging techniques are increasingly used to study mechanisms leading to cognitive impairment. In particular, brain atrophy has been proposed as a surrogate marker of dementia. However, little is known regarding confounding factors which might modulate the evolution of brain atrophy during ageing. We therefore determined the rate of atrophy over 6 years for 201 participants (F/M=96/105; 59.8±5.9 yrs) in the Austrian Stroke Prevention Study and probed the impact of baseline variables on its progression. The mean annual brain volume change was -0.40±0.29%. The rate of brain atrophy was significantly higher in subjects of greater age and those with higher HbA1c, higher body-mass-index, high alcohol intake, severe white matter hyperintensities, and in APOEε4-carriers. Multivariate analysis suggested that baseline brain volume, HbA1c and the extent of white matter hyperintensities explain a major proportion of variance in the rates of brain atrophy. These results indicate that neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. HbA1c was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called ""metabolic syndrome"" in subjects with high HbA1c suggests a link between this syndrome and late-life brain tissue loss. Together, this underscores the need to control for confounding factors in future Clinical trials and indicates possible new directions for intervention.",apolipoprotein E4;hemoglobin A1c;adult;aged;aging;alcohol consumption;article;Austria;body mass;brain atrophy;brain size;brain tissue;cohort analysis;controlled study;disease course;disease severity;female;follow up;heterozygote;human;major clinical study;male;metabolic syndrome X;multivariate analysis;nuclear magnetic resonance imaging;risk factor;cerebrovascular accident;white matter,"Enzinger, C.;Fazekas, F.;Matthews, P. M.;Ropele, S.;Schmidt, H.;Smith, S.;Schmidt, R.",2006,,,0,
4495,Diffusion tensor MRI post mortem demonstrated cerebral white matter pathology [3],,Alzheimer disease;brain disease;case report;diagnostic imaging;diffusion tensor imaging;human;human tissue;letter;neurologic disease;neuroradiology;nuclear magnetic resonance imaging;priority journal;white matter;Magnetom Allegra,"Englund, E.;Sjöbeck, M.;Brockstedt, S.;Lätt, J.;Larsson, E. M.",2004,,,0,
4496,Diffusion tensor MRI post mortem demonstrated cerebral white matter pathology,,"Dementia/pathology;Diffusion Magnetic Resonance Imaging/*methods;Humans;Nerve Fibers, Myelinated/*pathology;Statistics, Nonparametric;Telencephalon/*pathology","Englund, E.;Sjobeck, M.;Brockstedt, S.;Latt, J.;Larsson, E. M.",2004,Mar,10.1007/s00415-004-0318-2,0,
4497,Correlations between histopathologic white matter changes and proton MR relaxation times in dementia,"Our previous studies have shown that incomplete white matter infarctions are common in senile dementia of the Alzheimer type. To visualize and interpret these changes on magnetic resonance imaging (MRI), knowledge of MR relaxation times associated with this histopathology is important. The proton MR relaxation times T1 and T2 were determined in vitro for 3 groups of specimens. Fifty specimens of normal and incompletely infarcted white matter from 21 patients with senile dementia and 38 normal and pathologic white matter specimens from 19 elderly cases with infarcts were analyzed. The specimens were evaluated for infarct type, grade of incomplete infarction, and the proportion of old complete or incomplete infarction versus normal tissue in each sample. The incomplete infarct had longer relaxation times than normal white matter, with prolongation of T1 and T2 being proportional to the severity of the tissue changes. Old complete infarcts had longer relaxation times than both normal white matter and incomplete infarctions. These differences in relaxation times, reflecting various degrees of tissue damage, are important for the interpretation of MR images in vivo. Visualization of incomplete infarctions is essential for an in vivo diagnosis of these frequent and sometimes extensive changes.","Alzheimer Disease/ pathology;Body Water/metabolism;Brain/metabolism/ pathology/radiography;Cerebral Infarction/pathology;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Tomography, X-Ray Computed","Englund, E.;Brun, A.;Persson, B.",1987,,,0,
4498,Neuropathology of white matter changes in Alzheimer's disease and vascular dementia,"Morphological white matter changes were investigated in clinically and neuropathologically diagnosed cases of Alzheimer's disease (AD; 60 cases) and vascular dementia (VaD; 40 cases). In 33 of 60 AD cases, a white matter disease (WMD) characterized by tissue rarefaction, mild gliosis and a non-amyloid small-vessel sclerosis occurred in the central, preferentially frontal deep white matter. The mean vessel density was significantly lower than in normal control case frontal white matter. The presence of WMD did not parallel the severity of grey matter Alzheimer encephalopathy. In 25 of 60 AD cases, white matter degeneration with signs of both condensation and rarefaction of tissue elements was seen subjacent to advanced cortical degeneration in the temporal lobes. It concurred with WMD in only 13 cases and was judged to be of anterograde, Wallerian type and not related to angiopathy. In VaD, similar changes occurred, accompanied by several types of focal and topographically related lesions. For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases. For the recognition of such subtle variations in the spectrum of WMD, modern imaging techniques are crucial for detailed clinical diagnosis and attempts at therapeutic intervention.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Blood Vessels/pathology;Brain/ pathology;Dementia, Vascular/ pathology;Female;Humans;Immunohistochemistry;Male;Middle Aged;Nerve Degeneration/pathology","Englund, E.",1998,Jul,,0,
4499,Binswanger's disease and quantitative fractional anisotropy,"OBJECTIVE: To study the integrity of the white matter in Binswanger's disease (BD) patients with quantitative fractional anisotropy (DTI-FA). METHOD: Controls (12) and patients with BD (12) were included. Scans performed with MR (GE Signa Horizon/1.5T). Fazekas's score=6 with white matter hyperintensities extension >75% assessed on FLAIR scans. Standard parameters for DTI-FA were used. ROIs placed in symmetrical regions on two axial planes, data pooled in anterior (frontal) and posterior (temporo-parieto-occipital) regions. Analysis with Functool. Statistics for anterior and posterior regions comparison. RESULTS: DTI-FA showed reduction of anisotropy, reflecting axonal damage and demyelination of fibers, more prominent in anterior in relation to posterior region, in BD patients in comparison to controls. CONCLUSION: Loss of integrity of fiber tracts reflects interruption of neural networks that subserve cognitive, behavioral, and motor integration. The more severely affected frontal region is related to executive dysfunction, a characteristic feature of Binswanger's disease.","Aged;Anisotropy;Brain/*pathology;Case-Control Studies;Dementia, Vascular/*pathology;Female;Humans;Magnetic Resonance Imaging;Male","Engelhardt, E.;Moreira, D. M.;Alves, G. S.;Lanna, M. E.;Alves, C. E.;Ericeira-Valente, L.;Sudo, F. K.;Laks, J.",2009,Jun,,0,
4500,Does computed tomographic brain imaging have a place in the diagnosis of dementia?,"Background. - Computed tomographic (CT) scanning of the head is an accepted routine in the evaluation of dementia. This study attempted to identify a patient group in which brain imaging adds meaningful data to the clinical picture. Methods. - One hundred patients who met criteria for dementia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, underwent computed tomographic imaging. From clinical data alone, 56 of these patients also met the following strict criteria for the diagnosis of probable Alzheimer's disease (PAD): the McKhann criteria for PAD, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria for primary degenerative dementia, a score of less than 4 on the modified Hachinski Ischemia Scale, a normal neurologic examination and symptoms for at least 1 year. Results. - In the PAD group, eight scans (14%) had abnormalities other than atrophy; only three (two showing lacunae and one showing infarct) were of possible clinical significance. In the 44 patients not meeting PAD criteria, 23 scans (52%) were abnormal, including 15 with infarcts, two with periventricular lucencies, three showing tumors, and one showing hydrocephalus. Conclusions. - These results support the diagnostic value of computed tomographic scanning in atypical dementia and its limited utility in PAD. The data indicate that clinical guidelines can be developed for the application of CT in the diagnosis of dementia.",,"Engel, P. A.;Gelber, J.",1992,1992,,0,
4501,Single photon emission computed tomography in dementia: relationship of perfusion to cognitive deficits,"Sixteen patients with dementia (nine with Alzheimer's disease and seven with multi-infarct dementia) were studied with xenon-133 and hexamethyl-propyleneamine-oxime single photon emission computed tomography (SPECT). Quantification of cerebral blood flow was determined in 16 hemispheric regions of interest. Neuropsychological deficits were assessed with the Mini-Mental State Examination and the Neurobehavior Cognitive Status Examination. Alzheimer's disease patients had symmetric reduction of parietal lobe perfusion; multi-infarct dementia patients had multifocal perfusion deficits. Correlations were demonstrated between cerebral blood flow in the posterior brain regions and performance on tests of language, memory, attention, figure copying, judgment, and similarities. Alzheimer's disease patients exhibited more language impairment than multi-infarct dementia patients. SPECT promises to provide diagnostic information and data relevant to interpretation of neuropsychological deficits.","Aged;Brain/blood supply/physiopathology/*radionuclide imaging;Cerebrovascular Circulation;Cognition Disorders/complications/physiopathology/*radionuclide imaging;Dementia/complications/physiopathology/*radionuclide imaging;Female;Functional Laterality;Humans;Language Disorders/complications/physiopathology;Male;Neuropsychological Tests;Occipital Lobe/blood supply/physiopathology;Parietal Lobe/blood supply/physiopathology;Psychiatric Status Rating Scales;Temporal Lobe/blood supply/physiopathology;*Tomography, Emission-Computed, Single-Photon","Engel, P.;Cummings, J. L.;Villanueva-Meyer, J.;Mena, I.",1993,Jul-Sep,,0,
4502,Plasmapheresis Responsive Rapid Onset Dementia with Predominantly Frontal Dysfunction in the Context of Hashimoto's Encephalopathy,"Background: Hashimoto's encephalopathy (HE) is a rare immunological neuropsychiatric disorder characterized by increased antithyroid antibodies and mixed neurological and psychiatric symptoms. HE has been previously discussed as a differential diagnosis for rapid progressive dementia. However, most of these patients suffered from additional neurological symptoms, like ataxia or seizures. Case presentation: Here, we present the case of a 59-year-old female patient suffering rapid onset dementia with salient frontal executive dysfunction. She developed rapid onset symptoms, including apathy, verbal depletion up to a stuporous state, severe working memory deficits, evidence of primitive reflexes, disturbed Luria's three-step test, and micturition disorder. Analysis of her cerebrospinal fluid was normal. The serum analyses showed increased antithyroid (antithyroid peroxidase and antithyroglobulin) antibodies. In the cerebral magnetic resonance imaging, supratentorial deep and peripheral white matter lesions were found; the electroencephalography showed intermittent slowing, and the [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) depicted medial and superior dorsolateral frontal hypometabolism. Several different psychopharmacological therapeutic approaches with various neuroleptics, antidepressants, and high doses of lorazepam were unsuccessful. Due to the organic alterations, including increased antithyroid antibodies, HE was suspected. Against expectations, treatment with high-dose corticosteroids proved to be ineffective and was associated with worsening symptoms. However, escalated treatment with plasmapheresis over 5 days led to significant improvement in all reported symptoms and in psychometric testing. The neuropsychological improvement was stable over a 6-month follow-up period, and the FDG-PET normalized. Conclusion: This case report reveals that (1) HE can mimic rapid onset dementia with predominantly frontal dysfunction; (2) this syndrome can be successfully treated in the context of HE; and (3) plasmapheresis can be effective in such a disease constellation. The detection of the immunological causes of rapid onset dementia and other psychiatric syndromes is important because it opens opportunities for new, innovative immunosuppressive treatment options.",Hashimoto's encephalopathy;Sreat;frontotemporal dementia;plasmapheresis;thyroid,"Endres, D.;Vry, M. S.;Dykierek, P.;Riering, A. N.;Lungen, E.;Stich, O.;Dersch, R.;Venhoff, N.;Erny, D.;Mader, I.;Meyer, P. T.;Tebartz van Elst, L.",2017,,,0,
4503,Magnetic resonance imaging in alcoholic Korsakoff's syndrome: evidence for an association with alcoholic dementia,"A magnetic resonance imaging study of 19 alcoholic Korsakoff patients, 17 non-amnesic alcoholics and 23 non-alcoholic controls was undertaken. Several measures of ventricular size and interhemispheric area were significantly greater in the Korsakoff patients. Interhemispheric fissure size was greater in the non-amnesic alcoholics than the non-alcoholic controls. Cortical grey matter T1 values were essentially the same for the three groups, whereas the deep grey and the white matter T1 values for the Korsakoff patients were significantly greater than the non-alcoholic controls. These results indicate widespread cerebral atrophy in alcoholic Korsakoff patients, which is largely subcortical and does not develop independently of the diencephalic pathology. Alcoholic dementia may be a more severe form of alcoholic Korsakoff syndrome, aetiologically related to the nutritionally-induced diencephalic pathology, rather than the neurotoxic effects of alcohol on the cortex.","Adult;Alcohol Amnestic Disorder/diagnosis/ pathology;Alcoholism/diagnosis/ pathology;Atrophy;Brain/ pathology;Caudate Nucleus/pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Dementia/diagnosis/ pathology;Diencephalon/pathology;Dominance, Cerebral/physiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Psychoses, Alcoholic/diagnosis/ pathology","Emsley, R.;Smith, R.;Roberts, M.;Kapnias, S.;Pieters, H.;Maritz, S.",1996,Sep,,0,
4504,Corpus callosum macro and microstructure in late-life depression,"BACKGROUND: Differences in corpus callosum (CC) morphology and microstructure have been implicated in late-life depression and may distinguish between late and early-onset forms of the illness. However, a multimodal approach using complementary imaging techniques is required to disentangle microstructural alterations from macrostructural partial volume effects. METHODS: 107 older adults were assessed: 55 currently-depressed patients without dementia and 52 controls without cognitive impairment. We investigated group differences and clinical associations in 7 sub-regions of the mid-sagittal corpus callosum using T1 anatomical data, white matter hyperintensity (WMH) quantification and two different diffusion MRI (dMRI) models (multi-tissue constrained spherical deconvolution, yielding apparent fibre density, AFD; and diffusion tensor imaging, yielding fractional anisotropy, FA and radial diffusivity, RD). RESULTS: Callosal AFD was lower in patients compared to controls. There were no group differences in CC thickness, surface area, FA, RD, nor whole brain or WMH volume. Late-onset of depression was associated with lower FA, higher RD and lower AFD. There were no associations between any imaging measures and psychotic features or depression severity as assessed by the geriatric depression scale. WMH volume was associated with lower FA and AFD, and higher RD in patients. LIMITATIONS: Patients were predominantly treatment-resistant. Measurements were limited to the mid-sagittal CC. dMRI analysis was performed on a smaller cohort, n=77. AFD was derived from low b-value data. CONCLUSIONS: Callosal structure is largely preserved in LLD. WMH burden may impact on CC microstructure in late-onset depression suggesting vascular pathology has additional deleterious effects in these patients.",Corpus callosum;Depression;Diffusion;Late-life;Mri;White matter,"Emsell, L.;Adamson, C.;De Winter, F. L.;Billiet, T.;Christiaens, D.;Bouckaert, F.;Adamczuk, K.;Vandenberghe, R.;Seal, M. L.;Sienaert, P.;Sunaert, S.;Vandenbulcke, M.",2017,Nov,,0,
4505,MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias,"OBJECTIVE: The purpose of this study was to investigate age-corrected brain MR elastography (MRE) findings in four dementia cohorts (Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia, and normal pressure hydrocephalus) and determine the potential use as a differentiating biomarker in dementia subtypes. SUBJECTS AND METHODS: Institutional review board approval and written informed consent were obtained to perform MRE on 84 subjects: 20 patients with normal pressure hydrocephalus, eight with Alzheimer disease, five with dementia with Lewy bodies, five with frontotemporal dementia, and 46 cognitively normal control subjects. Shear waves of 60-Hz vibration frequency were transmitted into the brain using a pillowlike passive driver, and brain stiffness was determined in eight different regions (cerebrum, frontal, occipital, parietal, temporal, deep gray matter-white matter, sensorimotor cortex, and cerebellum). All stiffness values were age-corrected and compared with control subjects. The Wilcoxon rank sum test and linear regression were used for statistical analysis. RESULTS: Regional stiffness patterns unique to each dementing disorder were observed. Patients with Alzheimer disease and frontotemporal dementia showed decreased cerebral stiffness (p = 0.001 and p = 0.002, respectively) with regional softening of the frontal and temporal lobes. Patients with Alzheimer disease additionally showed parietal lobe and sensorimotor region softening (p = 0.039 and p = 0.018, respectively). Patients with normal pressure hydrocephalus showed stiffening of the parietal, occipital, and sensorimotor regions (p = 0.007, p < 0.001, and p < 0.0001, respectively). Patients with dementia with Lewy bodies did not show significant stiffness changes in any of the regions. CONCLUSION: Quantitative MRE of changes in brain viscoelastic structure shows unique regional brain stiffness patterns between common dementia subtypes.","Aged;Aged, 80 and over;Brain/ diagnostic imaging/ physiopathology;Dementia/ diagnostic imaging/ physiopathology;Echo-Planar Imaging;Elasticity Imaging Techniques;Female;Humans;Image Interpretation, Computer-Assisted/methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;MR elastography;brain stiffness;dementia","ElSheikh, M.;Arani, A.;Perry, A.;Boeve, B. F.;Meyer, F. B.;Savica, R.;Ehman, R. L.;Huston, J., 3rd",2017,Aug,,0,
4506,Mild brain atrophy in early HIV infection: the lack of association with cognitive deficits and HIV-specific intrathecal immune response,"Brain MRI and/or CT were performed on 72 HIV-infected patients at various stages of the disease, and on 34 controls. The neuroradiological findings were related to duration of the infection, neurological symptoms, and cognitive abnormalities as well as to immunological findings in the CSF and blood. All types of brain atrophy were more severe and more frequent in HIV-infected subjects than in controls. Patients with neurological symptoms, those with advanced HIV infection, and patients with a duration of HIV infection of more than 4 years showed the most severe and most frequent neuroradiological abnormalities, including central and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Subjects with cognitive defects exhibited more severe central atrophy than cognitively intact patients. However, slight brain atrophy and/or parenchymal lesions were found in 57% of cognitively intact HIV-seropositive individuals. Patients with brain atrophy and those with radiologically normal brain, both showed increased intrathecal synthesis of total IgG, and intrathecal HIV-antibody synthesis. However, a declined general immune response and a lowered CSF leukocyte count were seen predominantly in patients with brain atrophy. The results suggest that subcortical, neurologically ""silent"" areas of brain white matter are an early target of HIV infection.","AIDS Dementia Complex/complications/pathology/radiography;Adult;Atrophy;Brain/*pathology/radiography;CD4-Positive T-Lymphocytes;Cognition Disorders/etiology/*pathology;Female;HIV/immunology;HIV Antibodies/*cerebrospinal fluid;HIV Infections/*pathology;Humans;Immunoglobulin G/*cerebrospinal fluid;Magnetic Resonance Imaging;Male;Middle Aged;Tomography, X-Ray Computed","Elovaara, I.;Poutiainen, E.;Raininko, R.;Valanne, L.;Virta, A.;Valle, S. L.;Lahdevirta, J.;Iivanainen, M.",1990,Nov,,0,
4507,Genetic and environmental influences on cortical mean diffusivity,"Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinical relevance, we examined the genetic and environmental influences on cortical MD in middle-aged men to provide support for the biological relevance of this measure and to guide future gene association studies. It is not clear whether individual differences in cortical MD reflect neuroanatomical variability similarly detected by other MRI measures, or whether unique features are captured. For instance, variability in cortical MD may reflect morphological variability more commonly measured by cortical thickness. Differences among individuals in cortical MD may also arise from breakdowns in myelinated fibers running through the cortical mantle. Thus, we investigated whether genetic influences on variation in cortical MD are the same or different from those influencing cortical thickness and MD of white matter (WM) subjacent to the cortical ribbon. Univariate twin analyses indicated that cortical MD is heritable in the majority of brain regions; the average of regional heritability estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital cortex, consistent with the heritability of other MRI measures of the brain. Trivariate analyses found that, while there was some shared genetic variance between cortical MD and each of the other two measures, this overlap was not complete (i.e., the correlation was statistically different from 1). A significant amount of distinct genetic variance influences inter-individual variability in cortical MD; therefore, this measure could be useful for further investigation in studies of neurodegenerative diseases and gene association studies.",Cortex;Heritability;Magnetic resonance imaging;Mean diffusivity;Twins,"Elman, J. A.;Panizzon, M. S.;Hagler, D. J., Jr.;Fennema-Notestine, C.;Eyler, L. T.;Gillespie, N. A.;Neale, M. C.;Lyons, M. J.;Franz, C. E.;McEvoy, L. K.;Dale, A. M.;Kremen, W. S.",2017,Feb 01,,0,
4508,The role of neuroradiology in senile dementia,"The neuroradiological approach to the aging brain and the neurodegenerative disorders is still a challenge, mostly because of the aspecificity of the findings, similar in many diseases. The most common technique, CT, is the first choice for the diagnosis of the dementia. Unfortunately it is relevant only when a significant neuronal loss is present. MRI is definitively more useful for its high resolution and especially because it allows a better differentiation among white matter structures. The limit is its aspecificity. Nuclear medicine techniques (expecially SPECT and PET) represent a new possibility in the diagnostic imaging of dementia, in particular, PET is highly sensitive when CT and MRI are still normal, but the elevated cost and few number of machines available limit the routinary use of this technique. To date, neuroradiological studies are only to be considered a support for the clinical investigation, until further technological progress will solve the limit observed at this moment.",,"Elefante, A.",1994,1994,,0,
4509,Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up,"OBJECTIVE: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. METHODS: From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70-82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. RESULTS: Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). CONCLUSION: Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity.","Atrophy;Brain [pathology];Cognition Disorders [etiology] [pathology] [psychology];Diabetes Complications [pathology] [psychology];Diabetes Mellitus, Type 2 [pathology] [psychology];Follow-Up Studies;Hydroxymethylglutaryl-CoA Reductase Inhibitors [therapeutic use];Hyperglycemia [complications] [pathology];Hypoglycemic Agents [adverse effects] [therapeutic use];Insulin [adverse effects] [therapeutic use];Linear Models;Magnetic Resonance Imaging;Neuropsychological Tests;Pravastatin [therapeutic use];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-endoc: sr-stroke","Elderen, S. G.;Roos, A.;Craen, A. J.;Westendorp, R. G.;Blauw, G. J.;Jukema, J. W.;Bollen, E. L.;Middelkoop, H. A.;Buchem, M. A.;Grond, J.",2010,,10.1212/WNL.0b013e3181f25f06,0,
4510,Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease,"BACKGROUND: Degradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD. OBJECTIVE: To quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI). METHODS: 60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%). RESULTS: All FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups. CONCLUSIONS: All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.",Ad;Behavioral variant FTD;Clinical trial;Dti;Ftd;Longitudinal;Primary progressive aphasia;Sample size;White matter integrity,"Elahi, F. M.;Marx, G.;Cobigo, Y.;Staffaroni, A. M.;Kornak, J.;Tosun, D.;Boxer, A. L.;Kramer, J. H.;Miller, B. L.;Rosen, H. J.",2017,,,0,
4511,Cerebral small vessel disease and cognition,"Background: Cerebral small vessel disease (SVD) is one of the frequent findings on CT and MRI scans of elderly people and is related to vascular risk factors, cognitive and motor impairment. Objective: The objective of the present study is to evaluate cognitive impairment associated with small vessel disease. Methods: This is a case-control study where consecutive non-demented patients with confluent leukoaraiosis on MRI were recruited to assess the cognitive impairment associated with SVD (n=40), and underwent neuropsychological assessment and multimodal brain MRI. Control group included healthy volunteers who were age, sex and education level matched (n=10). Results: The performance of the patient group was lower than the control group in Addenbrooke test, verbal fluency test, trail making B test, Digit symbol test (DST), Paired Associate Learning Test (PALT) and block design test and these statistical differences were highly significant (P-value < 0.01), a statistically significant difference between the 2 groups was also found in trail making A test (P-value < 0.05). The duration of the vascular risk factors of the SVD (hypertension and diabetes mellitus) and the grades of Fazeka's scale were negatively correlated with the performance of the patient group in all of the cognitive tests Conclusion: Cerebral Small vessel disease is associated with cognitive impairment affecting mainly verbal fluency, language skills and executive functions.",Addenbrooke test;adult;age distribution;aged;article;block design test;brain radiography;case control study;cerebrovascular disease;clinical article;cognitive defect;communication skill;controlled study;cross-sectional study;diabetes mellitus;digit symbol substitution test;disease association;disease duration;executive function;Fazeka Scale;female;human;hypertension;leukoaraiosis;male;neurologic disease assessment;neuropsychological test;nuclear magnetic resonance imaging;Paired Associate Learning Test;speech articulation;verbal fluency test,"El Serafy, O.;Al Awwady, M. E. S.;Nada, M. A. F.;Hassan, A.;Reda, A.",2015,,,0,
4512,Magnetic resonance imaging and the acquired immunodeficiency syndrome dementia complex,"It is now recognized that patients infected by the virus linked to the acquired immunodeficiency syndrome (AIDS) can develop dementia symptoms as the initial and sometimes only symptomatology for AIDS. This appears to be a syndrome whose origin is independent of secondary non-viral infection or malignancy. Magnetic resonance imaging (MRI) in three patients with well documented AIDS dementia revealed high signal periventricular white matter lesions. In one case, large lesions were not apparent on computed tomography and gross inspection of the fixed brain prior to autopsy. In two cases in which serial in vivo MR studies were obtained, there was a progressive increase in lesion volume over a short (several months) period of observation. Periventricular white matter lesions may be an early sign accompanying AIDS dementia, and the degree of changes correlated well with the clinical picture in our patients.",,"Ekholm, S.;Simon, J. H.",1988,1988,,0,
4513,Bace inhibitor verubecestat (MK-8931): baseline characteristics for participants enrolled in the phase II/III epoch alzheimer's disease trial,"Background: Verubecestat (MK-8931) is a potent, oral beta-secretase 1 inhibitor currently in development for treatment of Alzheimer's disease (AD). Verubecestat reduces Abeta levels by over 80% in cerebrospinal fluid (CSF) and brain of rodents and primates, and as well as CSF in subjects with AD. Verubecestat is therefore being evaluated for its ability to slow AD progression. A Phase II/III trial (EPOCH) is testing verubecestat in mild-to-moderate AD and has completed enrollment. Baseline clinical characteristics are presented below. Methods: EPOCH (clinicaltrials.gov NCT01739348) is an ongoing randomized, double- blind, placebo-controlled trial in mild-to-moderate AD. Key entry criteria included: diagnosis of probable AD (based on NINCDS-ADRDA and DSM-IV-TR criteria); MMSE of 15-26; MRI/CT findings consistent with AD; a trial partner with frequent contact with participant; and no uncontrolled medical conditions. Use of a stable dose of acetylcholinesterase inhibitors (AChEI) and memantine is permitted. Exclusion criteria included modified Hachinski>4, severe white matter disease, and other active neurological/ psychiatric disorders. Co-primary outcome measures are change from baseline in ADAS-Cog and ADCS-ADL scores at Week 78. Results: 2,211 participants were randomized between 2012 and 2015 from 239 sites in 21 countries worldwide, with 44% recruited from US/Canada, 31% from Europe/Australia/ New Zealand, 13% from Japan, and 12% from other countries. Screening failure was 34%. Preliminary baseline demographic data include the following: 55% female, mean (SD) age of 71.8 (7.5) years, 80% white race (17% Asian, 3% other) and 10% Hispanic or Latino. Most participants (89%) had been diagnosed with AD for at least six months before study entry. Most (88%) were on AChEI and/or memantine therapy. Regarding education level, 40% had 16 or more years. Enrollment was balanced regarding baseline disease severity: 48% mild (MMSE >21) and 52% moderate (MMSE < 20). Approximately 62% were APOE4 positive. Mean (SD) baseline scores for the key efficacy measures were ADAS-Cog: 21.4 (7.5), ADCS-ADL: 62.6 (10.0), CDR-SB: 5.4 (2.2) and MMSE: 20.3 (3.3). Conclusions: Baseline characteristics of the population included in the EPOCH trial are similar to those from prior published trials in participants with mild-to-moderate AD.","aged;Alzheimer disease;Australia;Canada;Caucasian;clinical trial;controlled clinical trial;controlled study;daily life activity;demography;diagnosis;double blind procedure;drug therapy;DSM-IV-TR;education;Europe;female;Hispanic;human;Japan;major clinical study;male;Mini Mental State Examination;New Zealand;nuclear magnetic resonance imaging;phase 2 clinical trial;phase 3 clinical trial;randomized controlled trial;screening;white matter;5,6 dihydro 2 imino 3 methyl 6 [4 [5 (1 propynyl) 3 pyridinyl] 2 thienyl] 4 pyrimidinone;apolipoprotein E;cholinesterase inhibitor;endogenous compound;memantine;placebo;recombinant erythropoietin;verubecestat","Egan, M.;Voss, T.;Mo, Y.;Mukai, Y.;Furtek, C.;Kost, J.;Aisen, P. S.;Cummings, J. L.;Tariot, P. N.;Vellas, B.;Michelson, D.",2017,,,0,
4514,Antihypertensive Treatment is associated with MRI-Derived Markers of Neurodegeneration and Impaired Cognition: A Propensity-Weighted Cohort Study,"BACKGROUND: Hypertension is an important risk factor for Alzheimer's disease (AD) and cerebral small vessel disease. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are common anti-hypertensive treatments, but have differential effects on cortical amyloid. OBJECTIVE: The objective of this study was to evaluate associations between anti-hypertensive treatment, brain volume, and cognition, using a propensity-weighted analysis to account for confounding by indication. METHODS: We identified a cohort of normal elderly adults and individuals with mild cognitive impairment (MCI) or AD (N = 886; mean age = 75.0) from the Alzheimer's Disease Neuroimaging Initiative. Primary outcomes were brain parenchymal fraction, total hippocampal volume, and white matter hyperintensity (WMH) volume. Secondary outcomes were standardized scores on neuropsychological tests. Propensity-weighted adjusted multivariate linear regression was used to estimate associations between anti-hypertensive treatment class and MRI volumes and cognition. RESULTS: Individuals treated with ARBs showed larger hippocampal volumes (R2 = 0.83, p = 0.05) and brain parenchymal fraction (R2 = 0.83, p = 0.01) than those treated with ACEIs. When stratified by diagnosis, this effect remained only in normal elderly adults and MCI patients, and a significant association between ARBs and lower WMH volume (R2 = 0.83, p = 0.03) emerged for AD patients only. ARBs were also associated with significantly better performance on tests of episodic and verbal memory, language, and executive function (all p < 0.05). CONCLUSIONS: Findings are consistent with evidence for a neuroprotective effect of treatment with ARBs for brain structure and cognition. This study has potential implications for the treatment of hypertension, particularly in elderly adults at risk of cognitive decline and AD.",Alzheimer's disease;angiotensin converting enzyme inhibitors;angiotensin receptor blockers;hypertension;white matter hyperintensities,"Edwards, J. D.;Ramirez, J.;Callahan, B. L.;Tobe, S. W.;Oh, P.;Berezuk, C.;Lanctot, K.;Swardfager, W.;Nestor, S.;Kiss, A.;Strother, S.;Black, S. E.;Alzheimer's Disease Neuroimaging, Initiative",2017,,,0,
4515,Atrial fibrillation is independently associated with brain atrophy and cognitive dysfunction,"Background: Atrial fibrillation (AF) is the most common serious cardiac arrhythmia, affecting approximately 1-2% of the population (Go et al. JAMA. 2001;285:2370-5). AF is associated with endothelial damage, low cardiac output, and the presence of cerebral microemboli or microinfarcts (Kalantarian et al. Ann Intern Med. 2014;161:650-8) and emerging data indicate that AF may also increase the risk of dementia, independent of clinical stroke (de Bruijn et al. JAMA Neurol. 2015;72:1288-94). However, few studies have evaluated associations between AF and markers of cerebral small vessel disease, including structural brain volumes and domain-specific cognitive function. Methods: We ascertained a cohort of healthy elderly adults and patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) with and without comorbid AF from Phase 1 of the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N=505; mean age=75.966.4; median CHADS2 score=1.0; proportion with AF on anticoagulation =15.7%). Primary outcomes were MRI-derived brain volumetrics including global atrophy, indexed by brain parenchymal fraction (BPF), and white matter hyperintensity (WMH) burden, and standardized scores on domain-specific cognitive tests. Multivariable linear regression was used to evaluate associations between a history of cardiac arrhythmia, including AF, and volumetric and cognitive outcomes. All models were adjusted for age, sex, diagnostic classification, baseline score on the Mini Mental State Exam, apolipoprotein E (APOE4) status, CHADS2 score, and for history of prior clinical stroke. Results: In elderly adults and patients with MCI and AD, a history of cardiac arrhythmias including AF was associated with a significant reduction in mean BPF (F=1.83, p=.03) and impaired performance on the Rey Auditory Verbal Learning Test (F=2.26, p=.03), and Trail Making Test B (F=2.09, p=.04), reflecting primarily verbal recognition and task-switching abilities, after adjustment for prior stroke. No associations were observed between AF and WMH burden or other standardized neuropsychological measures. Conclusions: AF is associated with brain atrophy and cognitive impairment independent of age, APOE4 status, and prior stroke (CHADS2 score). Trials evaluating structural and cognitive endpoints are required to determine the efficacy of treatments for AF for the prevention of progressive neurodegenerative and cognitive decline.",adult;aged;Alzheimer disease;anticoagulation;atrial fibrillation;brain atrophy;cerebrovascular accident;CHADS2 score;classification;controlled clinical trial;controlled study;human;linear regression analysis;major clinical study;mild cognitive impairment;Mini Mental State Examination;model;nuclear magnetic resonance imaging;phase 1 clinical trial;prevention;Rey auditory verbal learning test;trail making test;white matter;word recognition;apolipoprotein E;endogenous compound,"Edwards, J. D.;Ramirez, J.;Callahan, B. L.;Berezuk, C.;Gladstone, D. J.;Black, S. E.",2017,,,0,
4516,Unraveling the potential co-contributions of cerebral small vessel vasculopathy to the pathogenesis of Alzheimer's dementia,"Emerging evidence for the potential co-contributions of small vessel vasculopathy to dementia has resulted in a more nuanced view of Alzheimer's disease (AD) pathogenesis. Although cerebral small vessel disease, visualized on magnetic resonance imaging as hyperintense signal abnormalities, independently predicts the incidence and clinical progression of dementia, the relationships between AD pathology, white matter hyperintensity volume, genotype, and cognitive decline in AD remain unclear. The study by Morgen and colleagues, recently published in Alzheimer's Research & Therapy, presents important new findings on the associations between apolipoprotien E epsilon4 genotype, white matter hyperintensities, and cognition, independent of vascular risk, in a cohort of AD patients.",,"Edwards, J. D.;Ramirez, J.;Black, S. E.",2015,,10.1186/s13195-015-0133-2,0,
4517,"Dementia and Alzheimer disease incidence rates do not vary by sex in Rochester, Minn","Background: Incidence rates of Alzheimer disease (AD) were higher in women than in men in several recent European and Asian studies. Cohort studies in the United States, on the other hand, have consistently reported no difference in incidence across sex. Objective: To measure age- and sex-specific incidence rates of dementia and AD for persons aged 50 years and older residing in Rochester, Minn, during 1985 to 1989. Subjects and Methods: Cases were ascertained through the medical records linkage system of the Rochester Epidemiology Project, which encompasses the records of all medical care providers (including Outpatient clinics, hospitals, general practitioners, and nursing homes) in Rochester. Computer indices of clinical diagnoses, histologic diagnoses, and medical procedures were screened for indications of dementia. All medical records of potential cases were reviewed and abstracted by a trained nurse abstractor. A neurologist (E.K.) confirmed the presence of dementia and established a differential diagnosis of AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and estimated the year of onset. Results: A total of 482 incident cases of dementia were identified; 356 of them (73.9%) had AD. For both dementia and AD, incidence rates increased steeply with age, and there were no consistent differences between men and women. The sex pattern for AD did not change after removing cases with silent bilateral infarcts on imaging. Conclusions: Contrary to observations from European and Asian populations, women were not at increased risk of incident AD in Rochester. Our findings, based on a medical records linkage system, corroborate findings from several other US studies that involved the direct contact of cohort members. The consistency of findings across study designs suggests that sex or sex-related exposures do not consistently play a major role in AD causation in American populations.",,"Edland, S. D.;Rocca, W. A.;Petersen, R. C.;Cha, R. H.;Kokmen, E.",2002,1,,0,
4518,Comparison of MRI based and PET template based approaches in the quantitative analysis of amyloid imaging with PIB-PET,"RATIONALE: [(11)C]Pittsburgh compound-B (PIB) has been the most widely used positron emission tomography (PET) imaging agent for brain amyloid. Several longitudinal studies evaluating the progression of Alzheimer's disease (AD), and numerous therapeutic intervention studies are underway using [(11)C]PIB PET as an AD biomarker. Quantitative analysis of [(11)C]PIB data requires the definition of regional volumes of interest. This investigation systematically compared two data analysis routes both using a probabilistic brain atlas with 11 bilateral regions. Route 1 used individually segmented structural magnetic resonance images (MRI) for each subject while Route 2 used a standardised [(11)C]PIB PET template. METHODS: A total of 54 subjects, 20 with probable Alzheimer's disease (AD), 14 with amnestic Mild Cognitive Impairment (MCI) and 20 age-matched healthy controls, were scanned at two imaging centres either in London (UK) or in Turku (Finland). For all subjects structural volumetric MRI and [(11)C]PIB PET scans were acquired. Target-to-cerebellum ratios 40 min to 60 min post injection were used as outcome measures. Regional read outs for grey matter target regions were generated for both routes. Based on a composite neocortical, frontal, posterior cingulate, combined posterior cingulate and frontal cortical regions, scans were categorised into either 'PIB negative' (PIB-) or 'PIB positive' (PIB+) using previously reported cut-off target-to-cerebellar ratios of 1.41, 1.5 and 1.6, respectively. RESULTS: Target-to-cerebellum ratios were greater when defined with a [(11)C]PIB PET template than with individual MRIs for all cortical regions regardless of diagnosis. This difference was highly significant for controls (p<0.001, paired samples t-test), less significant for MCIs and borderline for ADs. Assignment of subjects to raised or normal categories was the same with both routes with a 1.6 cut-off while with lower cut off using frontal cortex, and combined frontal cortex and posterior cingulate demonstrated similar results, while posterior cingulate alone demonstrated significantly higher proportion of controls as amyloid positive by Route 2. CONCLUSIONS: Definition of cortical grey matter regions is more accurate when individually segmented MRIs (Route 1) were used rather than a population-based PET template (Route 2). The impact of this difference depends on the grey-to-white matter contrast in the PET images; specifically seen in healthy controls with high white matter and low grey matter uptake. When classifying AD, MCI and control subjects as normal or abnormal using large cortical regions; discordance was found between the MRI and template approach for those few subjects who presented with cortex-to-cerebellum ratios very close to the pre-assigned cut-off. However, posterior cingulate alone demonstrated significant discordance in healthy controls using template based approach. This study, therefore, demonstrates that the use of a [(11)C]PIB PET template (Route 2) is adequate for clinical diagnostic purposes, while MRI based analysis (Route 1) remains more appropriate for clinical research.",Aged;Alzheimer Disease/ diagnosis;Amyloid/ analysis;Aniline Compounds;Carbon Radioisotopes;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis;Positron-Emission Tomography;Thiazoles,"Edison, P.;Carter, S. F.;Rinne, J. O.;Gelosa, G.;Herholz, K.;Nordberg, A.;Brooks, D. J.;Hinz, R.",2013,Apr 15,10.1016/j.neuroimage.2012.12.014,0,
4519,High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment,"BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy. METHODS: The Gothenburg MCI study is a clinically based longitudinal study with biennial clinical assessments. The participants (n = 166) consist of 92 patients with stable MCI, 30 patients with converting MCI, and 44 healthy controls. WML volumes was measured manually using MRIcron. Automated segmentation of hippocampal and total white matter volumes was performed using FreeSurfer. RESULTS: The patients converting from MCI to dementia had reduced hippocampal volume. Stable MCI patients had fewer WML and converting MCI patients had more WML compared to controls. Hippocampal volume was only correlated to WML volume (rho = 0.57; p < 0.01) in the quartile (n = 42) with the most WML. CONCLUSIONS: Hippocampal atrophy is present in both AD and SVD. Hippocampal volume was associated with WML volume only in the high WML quartile, suggesting that the WML volume must reach a threshold before hippocampal atrophy is seen.","Aged;Alzheimer Disease/pathology/psychology;Apolipoproteins E/genetics;Atrophy;Brain/*pathology;Cognition Disorders/*pathology/psychology;Dementia, Vascular/pathology/psychology;Educational Status;Female;Hippocampus/*pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Eckerstrom, C.;Olsson, E.;Klasson, N.;Bjerke, M.;Gothlin, M.;Jonsson, M.;Rolstad, S.;Malmgren, H.;Wallin, A.;Edman, A.",2011,,10.1159/000323014,0,
4520,Multimodal prediction of dementia with up to 10 years follow up: the Gothenburg MCI study,"BACKGROUND: Neuropsychological tests, CSF Abeta42, T-tau, P-tau181, hippocampal volume, and white matter lesions have been shown to predict conversion to dementia in patients with mild cognitive impairment (MCI). OBJECTIVE: To examine the predictive value of combinations of these markers and to examine if the absence of pathological markers provides a lasting reduction of conversion rates. METHODS: The Gothenburg MCI study is a clinically based study. Seventy-three MCI patients were included in the present sub-study and followed for a maximum of ten years. Thirty-four patients converted to dementia (18 to AD) and 39 remained stable. At inclusion, patients were classified into positive or negative risk groups according to results from neuropsychological testing (Rey auditory verbal learning test, Boston naming test, Trail making test B), CSF biomarkers (amyloid beta42, T-tau, and P-tau181), and MRI scans (hippocampal volume, white matter lesions). RESULTS: Trail making test B (TMT-B) was the best single predictor for the prediction of dementia (AUC 0.89, HR 25), and T-tau was the best predictor of AD (AUC 0.97, HR 41). The combination of hippocampal volume and TMT-B was the best combination for the prediction of dementia (HR 25), and the combination of hippocampal volume and T-tau was the best combination for the prediction of AD (HR 37). CONCLUSION: Neuropsychological tests, CSF markers, and hippocampal volume predicted conversion from MCI to AD and general dementia. The absence of pathological markers provided a long-time protection from dementia.",Aged;Alzheimer Disease/cerebrospinal fluid/diagnosis;Amyloid beta-Peptides/ cerebrospinal fluid;Area Under Curve;Dementia/ cerebrospinal fluid/ diagnosis;Disease Progression;Female;Hippocampus/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/cerebrospinal fluid/diagnosis;Neuropsychological Tests;Predictive Value of Tests;tau Proteins/ cerebrospinal fluid,"Eckerstrom, C.;Olsson, E.;Klasson, N.;Berge, J.;Nordlund, A.;Bjerke, M.;Wallin, A.",2015,,10.3233/jad-141053,0,
4521,Temporal lobe abnormalities in dementia and depression: A study using high resolution single photon emission tomography and magnetic resonance imaging,"Objectives. Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities. Methods. Forty depressed patients (DSIM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker (99m)Tc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20°-30°. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width. Results. Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest. Conclusion. A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.",,"Ebmeier, K. P.;Prentice, N.;Ryman, A.;Halloran, E.;Ewen Rimmington, J.;Best, J. K. K.;Goodwin, G. M.",1997,November,,0,
4522,A voxel-based analysis of cerebral perfusion in dementia and depression of old age,"Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.","Aged;Aged, 80 and over;Alzheimer Disease/physiopathology/ radionuclide imaging;Basal Ganglia/blood supply/radionuclide imaging;Brain/ blood supply;Brain Mapping;Cerebral Cortex/blood supply/radionuclide imaging;Depressive Disorder, Major/physiopathology/ radionuclide imaging;Diagnosis, Differential;Dominance, Cerebral/physiology;Feasibility Studies;Humans;Image Processing, Computer-Assisted/ instrumentation;Mathematical Computing;Middle Aged;Reference Values;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/ instrumentation","Ebmeier, K. P.;Glabus, M. F.;Prentice, N.;Ryman, A.;Goodwin, G. M.",1998,Apr,10.1006/nimg.1998.0321,0,
4523,Nuclear magnetic resonance imaging and single photon emission tomography with radio-iodine labelled compounds in the diagnosis of dementia,"White matter lesions and T1 changes were identified using NMR and then compared between groups of patients suffering from dementia of the Alzheimer type (DAT), Multiple infarct dementia (MID) and normal controls. All DAT and MID patients were also imaged with a gamma camera using 123Iodo-n-isopropyl-amphetamine, a radiopharmaceutical whose uptake in the brain follows the regional blood flow. While NMR was not able to differentiate between DAT and MID, 19 out of 21 DAT patients compared to four out of 18 MID patients showed bilateral parietal lesions on IMP scans.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/radionuclide imaging;Amphetamines;Brain/ pathology;Cerebral Infarction/pathology;Dementia/ diagnosis/radionuclide imaging;Female;Humans;Iofetamine;Magnetic Resonance Spectroscopy;Male;Middle Aged;Parietal Lobe/pathology;Tomography, Emission-Computed","Ebmeier, K. P.;Besson, J. A.;Crawford, J. R.;Palin, A. N.;Gemmel, H. G.;Sharp, P. F.;Cherryman, G. R.;Smith, F. W.",1987,May,,0,
4524,Single-photon emission computed tomography studies of regional cerebral blood flow in multiple infarct dementia,,iofetamine i 123;aged;Alzheimer disease;article;brain blood flow;clinical article;diagnosis;female;human;male;multiinfarct dementia;normal human;single photon emission computer tomography,"Eberling, J. L.;Jagust, W. J.;Reed, B. R.;Kwo-on-Yuen, P. F.;Martin, E. M.",1992,,,0,
4525,Ensemble Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Complex Graph Measures from Diffusion Tensor Images,"The human brain is a complex network of interacting regions. The gray matter regions of brain are interconnected by white matter tracts, together forming one integrative complex network. In this article, we report our investigation about the potential of applying brain connectivity patterns as an aid in diagnosing Alzheimer's disease and Mild Cognitive Impairment (MCI). We performed pattern analysis of graph theoretical measures derived from Diffusion Tensor Imaging (DTI) data representing structural brain networks of 45 subjects, consisting of 15 patients of Alzheimer's disease (AD), 15 patients of MCI, and 15 healthy subjects (CT). We considered pair-wise class combinations of subjects, defining three separate classification tasks, i.e., AD-CT, AD-MCI, and CT-MCI, and used an ensemble classification module to perform the classification tasks. Our ensemble framework with feature selection shows a promising performance with classification accuracy of 83.3% for AD vs. MCI, 80% for AD vs. CT, and 70% for MCI vs. CT. Moreover, our findings suggest that AD can be related to graph measures abnormalities at Brodmann areas in the sensorimotor cortex and piriform cortex. In this way, node redundancy coefficient and load centrality in the primary motor cortex were recognized as good indicators of AD in contrast to MCI. In general, load centrality, betweenness centrality, and closeness centrality were found to be the most relevant network measures, as they were the top identified features at different nodes. The present study can be regarded as a ""proof of concept"" about a procedure for the classification of MRI markers between AD dementia, MCI, and normal old individuals, due to the small and not well-defined groups of AD and MCI patients. Future studies with larger samples of subjects and more sophisticated patient exclusion criteria are necessary toward the development of a more precise technique for clinical diagnosis.",Alzheimer's disease;diffusion tensor images;ensemble classification;graph measures;machine learning,"Ebadi, A.;Dalboni da Rocha, J. L.;Nagaraju, D. B.;Tovar-Moll, F.;Bramati, I.;Coutinho, G.;Sitaram, R.;Rashidi, P.",2017,,,0,
4526,What factors determine phenotype of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the context of a novel pathogenic R110C mutation in the NOTCH3 gene,"We report patients from a Polish family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who possess a novel heterozygous R110C mutation in exon 3 of the NOTCH3 gene leading to stereotypical cysteine loss. The proband had only seizure attacks and her magnetic resonance imaging (MRI) showed very numerous hyperintense foci in the cerebral white matter in a location characteristic of CADASIL. Distinctive ultrastructural assessment of vessels from skin-muscle biopsy revealed only mild degenerative changes but relatively numerous homogeneous deposits of granular osmiophilic material (GOM). In the other symptomatic family members with the same mutation ischaemic strokes were present but not epilepsy. In the proband's affected brother at a similar age, the brain MRI was normal but vessels showed pronounced degenerative changes and irregular GOM deposits. The present report not only extends the list of known pathogenic mutations responsible for CADASIL but also emphasizes clinical and morphologic variability among family members with the same NOTCH3 mutation, suggesting that probably additional factors, not only mutations, may influence the disease phenotype.",cysteine;Notch3 receptor;adult;article;blood vessel;brain ischemia;CADASIL;cause of death;clinical article;clinical feature;degeneration;epilepsy;exon;female;gene mutation;heterozygote;histopathology;human;male;middle aged;muscle biopsy;NOTCH3 gene;nuclear magnetic resonance imaging;phenotype;Polish citizen;seizure;skin biopsy;ultrastructure;white matter,"Dziewulska, D.;Sulejczak, D.;Wȩzyk, M.",2017,,10.5114/fn.2017.72387,0,
4527,Segmentation of age-related white matter changes in a clinical multi-center study,"Age-related white matter changes (WMC) are thought to be a marker of vascular pathology, and have been associated with motor and cognitive deficits. In the present study, an optimized artificial neural network was used as an automatic segmentation method to produce probabilistic maps of WMC in a clinical multi-center study. The neural network uses information from T1- and T2-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance (MR) scans, neighboring voxels and spatial location. Generalizability of the neural network was optimized by including the Optimal Brain Damage (OBD) pruning method in the training stage. Six optimized neural networks were produced to investigate the impact of different input information on WMC segmentation. The automatic segmentation method was applied to MR scans of 362 non-demented elderly subjects from 11 centers in the European multi-center study Leukoaraiosis And Disability (LADIS). Semi-manually delineated WMC were used for validating the segmentation produced by the neural networks. The neural network segmentation demonstrated high consistency between subjects and centers, making it a promising technique for large studies. For WMC volumes less than 10 ml, an increasing discrepancy between semi-manual and neural network segmentation was observed using the similarity index (SI) measure. The use of all three image modalities significantly improved cross-center generalizability compared to neural networks using the FLAIR image only. Expert knowledge not available to the neural networks was a minor source of discrepancy, while variation in MR scan quality constituted the largest source of error.","Aged;Aged, 80 and over;Aging/ physiology;Brain/ pathology;Humans;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging;Neural Networks (Computer)","Dyrby, T. B.;Rostrup, E.;Baare, W. F.;van Straaten, E. C.;Barkhof, F.;Vrenken, H.;Ropele, S.;Schmidt, R.;Erkinjuntti, T.;Wahlund, L. O.;Pantoni, L.;Inzitari, D.;Paulson, O. B.;Hansen, L. K.;Waldemar, G.",2008,Jun,10.1016/j.neuroimage.2008.02.024,0,
4528,Multimodal analysis of functional and structural disconnection in Alzheimer's disease using multiple kernel SVM,"Alzheimer's disease (AD) patients exhibit alterations in the functional connectivity between spatially segregated brain regions which may be related to both local gray matter (GM) atrophy as well as a decline in the fiber integrity of the underlying white matter tracts. Machine learning algorithms are able to automatically detect the patterns of the disease in image data, and therefore, constitute a suitable basis for automated image diagnostic systems. The question of which magnetic resonance imaging (MRI) modalities are most useful in a clinical context is as yet unresolved. We examined multimodal MRI data acquired from 28 subjects with clinically probable AD and 25 healthy controls. Specifically, we used fiber tract integrity as measured by diffusion tensor imaging (DTI), GM volume derived from structural MRI, and the graph-theoretical measures 'local clustering coefficient' and 'shortest path length' derived from resting-state functional MRI (rs-fMRI) to evaluate the utility of the three imaging methods in automated multimodal image diagnostics, to assess their individual performance, and the level of concordance between them. We ran the support vector machine (SVM) algorithm and validated the results using leave-one-out cross-validation. For the single imaging modalities, we obtained an area under the curve (AUC) of 80% for rs-fMRI, 87% for DTI, and 86% for GM volume. When it came to the multimodal SVM, we obtained an AUC of 82% using all three modalities, and 89% using only DTI measures and GM volume. Combined multimodal imaging data did not significantly improve classification accuracy compared to the best single measures alone.","Aged;Alzheimer Disease/ pathology/ physiopathology;Area Under Curve;Brain/ pathology/ physiopathology;Brain Mapping/methods;Diffusion Tensor Imaging/ methods;Female;Gray Matter/pathology/physiopathology;Humans;Magnetic Resonance Imaging/ methods;Male;Multimodal Imaging/ methods;Pattern Recognition, Automated/methods;Rest;Support Vector Machine","Dyrba, M.;Grothe, M.;Kirste, T.;Teipel, S. J.",2015,Jun,10.1002/hbm.22759,0,
4529,Robust automated detection of microstructural white matter degeneration in Alzheimer's disease using machine learning classification of multicenter DTI data,"Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer's disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6+/-5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naive Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample.",Aged;Alzheimer Disease/ complications;Artificial Intelligence;Brain/ pathology;Case-Control Studies;Diffusion Tensor Imaging;Female;Humans;Leukoencephalopathies/ diagnosis/ etiology;Male;Middle Aged;Principal Component Analysis;Reproducibility of Results;Retrospective Studies,"Dyrba, M.;Ewers, M.;Wegrzyn, M.;Kilimann, I.;Plant, C.;Oswald, A.;Meindl, T.;Pievani, M.;Bokde, A. L.;Fellgiebel, A.;Filippi, M.;Hampel, H.;Kloppel, S.;Hauenstein, K.;Kirste, T.;Teipel, S. J.",2013,,10.1371/journal.pone.0064925,0,
4530,Predicting Prodromal Alzheimer's Disease in Subjects with Mild Cognitive Impairment Using Machine Learning Classification of Multimodal Multicenter Diffusion-Tensor and Magnetic Resonance Imaging Data,"BACKGROUND: Alzheimer's disease (AD) patients show early changes in white matter (WM) structural integrity. We studied the use of diffusion tensor imaging (DTI) in assessing WM alterations in the predementia stage of mild cognitive impairment (MCI). METHODS: We applied a Support Vector Machine (SVM) classifier to DTI and volumetric magnetic resonance imaging data from 35 amyloid-beta42 negative MCI subjects (MCI-Abeta42-), 35 positive MCI subjects (MCI-Abeta42+), and 25 healthy controls (HC) retrieved from the European DTI Study on Dementia. The SVM was applied to DTI-derived fractional anisotropy, mean diffusivity (MD), and mode of anisotropy (MO) maps. For comparison, we studied classification based on gray matter (GM) and WM volume. RESULTS: We obtained accuracies of up to 68% for MO and 63% for GM volume when it came to distinguishing between MCI-Abeta42- and MCI-Abeta42+. When it came to separating MCI-Abeta42+ from HC we achieved an accuracy of up to 77% for MD and a significantly lower accuracy of 68% for GM volume. The accuracy of multimodal classification was not higher than the accuracy of the best single modality. CONCLUSIONS: Our results suggest that DTI data provide better prediction accuracy than GM volume in predementia AD.",,"Dyrba, M.;Barkhof, F.;Fellgiebel, A.;Filippi, M.;Hausner, L.;Hauenstein, K.;Kirste, T.;Teipel, S. J.",2015,Sep-Oct,10.1111/jon.12214,0,
4531,A close relationship between verbal memory and SN/VTA integrity in young and older adults,"Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR) - a measure of structural integrity - of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus. © 2008 Elsevier Ltd. All rights reserved.",,"Düzel, S.;Schütze, H.;Stallforth, S.;Kaufmann, J.;Bodammer, N.;Bunzeck, N.;Münte, T. F.;Lindenberger, U.;Heinze, H. J.;Düzel, E.",2008,November,,0,
4532,Basal forebrain integrity and cognitive memory profile in healthy aging,"Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. © 2009 Elsevier B.V. All rights reserved.",adult;aged;aging;article;cholinergic system;cognition;cognitive defect;controlled study;correlational study;cross-sectional study;dopaminergic system;factorial analysis;female;forebrain;frontal lobe;hippocampus;human;learning;male;neuromodulation;nuclear magnetic resonance imaging;priority journal;scoring system;substantia nigra;vascular disease;ventral tegmentum;white matter;working memory,"Düzel, S.;Münte, T. F.;Lindenberger, U.;Bunzeck, N.;Schütze, H.;Heinze, H. J.;Düzel, E.",2010,,,0,
4533,Neuroimaging in Alzheimer's disease: Preclinical challenges toward clinical efficacy,"The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 (19F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.",Alzheimer disease;anatomy;animal model;brain atrophy;diffusion tensor imaging;disease model;fluorine magnetic resonance imaging;hospital;human;model;molecular imaging;neuroimaging;white matter;amyloid beta protein;fluorine;manganese;nuclear magnetic resonance imaging agent,"Dustin, D.;Hall, B. M.;Annapragada, A.;Pautler, R. G.",2016,,,0,
4534,"Relationships between personality traits, medial temporal lobe atrophy and white matter lesion in subjects suffering from mild cognitive impairment","Mild Cognitive Impairment (MCI) is a heterogeneous cognitive status that can be a prodromal stage of Alzheimer's disease (AD). It is particularly relevant to focus on prodromal stages of AD such as MCI, because pathophysiological abnormalities of AD start years before the dementia stage. Medial temporal lobe atrophy (MTL) resulting from AD lesions and cerebrovascular lesions (i.e. white matter lesions (WML), lacunar strokes and strokes) are often revealed concurrently on Magnetic Resonance Imaging (MRI) in MCI subjects. Personality changes have been reported to be associated with MCI status and early AD. More specifically, an increase in neuroticism and a decrease in conscientiousness have been reported, suggesting that higher and lower scores, respectively in neuroticism and conscientiousness are associated with an increased risk of developing the disease. However, personality changes have not been studied concomitantly with pathological structural brain alterations detected on MRI in patients suffering from MCI. Therefore, the objective of the present study was to assess the relationship between MTL atrophy, WML, lacunar strokes and personality traits in such patients. The severity of WML was strongly associated with lower levels of conscientiousness and higher levels of neuroticism. Conversely, no association was detected between personality traits and the presence of lacunar strokes or MTL atrophy. Altogether, these results strongly suggest that personality changes occurring in a MCI population, at high risk of AD, are associated with WML, which can induce executive dysfunctions, rather than with MTL atrophy. © 2014 Duron, Vidal, Bounatiro, Ben_ahmed, Seux, Rigaud, Hanon, Viollet, Epelbaum and Martel.",,"Duron, E.;Vidal, J. S.;Bounatiro, S.;Ahmed, S. B.;Seux, M. L.;Rigaud, A. S.;Hanon, O.;Viollet, C.;Epelbaum, J.;Martel, G.",2014,,,0,
4535,[Relationship of white matter lesions on brain computed tomography and cognitive function in elderly subjects with mild cognitive impairment] Relations entre troubles cognitifs et lesions de la substance blanche cerebrale,"UNLABELLED: White matter lesions (WML) are frequently disclosed on elderly people computed tomography (CT) brain scan. OBJECTIVE: To evaluate the relationship between WML and cognitive functions of patients suffering from Mild Cognitive Impairment (MCI). METHODS: We studied the association between WML on CT brain scan and cognitive functions in 136 consecutive elderly subjects attending a geriatric outpatient clinic, suffering from MCI. The global cognitive assessment was based on Mini Mental State Examination (MMSE), a validated comprehensive battery of neuropsychological tests, the Cognitive Efficiency Profile (CEP), a CT brain scan and a complete biological screening. WML on CT brain scan was evaluated by a blinded investigator. RESULTS: In this population, 75 +/- 8 years of age, (women 60%, and hypertension 54%), 33% of subjects had WML on CT brain scan. Patients with WML were significantly older (OR=1.27; IC 95%=1.04 - 1.22), had more frequently a past history of hypertension (OR=2.71; IC 95%=1.06 - 6.96) and more frequently lacunae associated with WML (OR=4.48; IC 95%=1.18 - 16.99). Subjects with WML had significantly poorer cognitive functions than those without WML (CEP score/100=62.33 +/- 13.58 versus 71.87 +/- 14.19, p<0.01 and MMSE score/30=27.02 +/- 2.34 versus 27.97 +/- 1.89, p<0.01) CONCLUSION: Our results showed a relationship between WML on CT brain scan and the depth of cognitive dysfunction among MCI patients. Further long term prospective studies have to be performed to determinate if WML are involved in transitions between MCI and Alzheimer' s disease.","Age Factors;Aged;Brain/ diagnostic imaging;Brain Infarction/complications/diagnostic imaging;Cognition Disorders/ complications;Female;Humans;Hypertension/complications;Male;Neuropsychological Tests;Prospective Studies;Tomography, X-Ray Computed","Duron, E.;Alami, A.;Pequignot, R.;Bert, P.;Rigaud, A. S.;Hanon, O.",2007,Aug,,0,
4536,Relationship between white matter lesions on brain computed tomography and cognitive function in elderly subjects whit mild cognitive impairment,"White matter lesions (WML) are frequently disclosed on elderly people computed tomography (CT) brain scan. Objective: To evaluate the relationship between WML and cognitive functions of patients suffering from Mild Cognitive Impairment (MCI). Methods: We studied the association between WML on CT brain scan and cognitive functions in 136 consecutive elderly subjects attending a geriatric outpatient clinic, suffering from MCI. The global cognitive assessment was based on Mini Mental State Examination (MMSE), a validated comprehensive battery of neuropsychological tests, the Cognitive Efficiency Profile (CEP), a CT brain scan and a complete biological screening. WML on CT brain scan was evaluated by a blinded investigator. Results: In this population, 75 ± 8 years of age, (women 60%, and hypertension 54%), 33% of subjects had WML on CT brain scan. Patients with WML were significantly older (OR = 1.27; IC 95% = 1.04 - 1.22), had more frequently a past history of hypertension (OR = 2.71; IC 95% = 1.06 - 6.96) and more frequently lacunae associated with WML (OR = 4.48; IC 95% = 1.18 - 16.99). Subjects with WML had significantly poorer cognitive functions than those without WML (CEP score/100 = 62.33 ± 13.58 versus 71.87 ± 14.19, p < 0.01 and MMSE score/30 = 27.02 ± 2.34 versus 27.97 ± 1.89, p < 0.01) Conclusion: Our results showed a relationship between WML on CT brain scan and the depth of cognitive dysfunction among MCI patients. Further long term prospective studies have to be performed to determinate if WML are involved in transitions between MCI and Alzheimer' s disease. © 2007. Elsevier Masson SAS.",aged;article;brain scintiscanning;cognition;cognitive defect;computer assisted tomography;controlled study;female;human;major clinical study;male;Mini Mental State Examination;white matter,"Duron, E.;Alami, A.;Pequignot, R.;Bert, P.;Rigaud, A. S.;Hanon, O.",2007,,,0,
4537,[Relationship of white matter lesions on brain computed tomography and cognitive function in elderly subjects with mild cognitive impairment],"White matter lesions (WML) are frequently disclosed on elderly people computed tomography (CT) brain scan. OBJECTIVE: To evaluate the relationship between WML and cognitive functions of patients suffering from Mild Cognitive Impairment (MCI). METHODS: We studied the association between WML on CT brain scan and cognitive functions in 136 consecutive elderly subjects attending a geriatric outpatient clinic, suffering from MCI. The global cognitive assessment was based on Mini Mental State Examination (MMSE), a validated comprehensive battery of neuropsychological tests, the Cognitive Efficiency Profile (CEP), a CT brain scan and a complete biological screening. WML on CT brain scan was evaluated by a blinded investigator. RESULTS: In this population, 75 +/- 8 years of age, (women 60%, and hypertension 54%), 33% of subjects had WML on CT brain scan. Patients with WML were significantly older (OR=1.27; IC 95%=1.04 - 1.22), had more frequently a past history of hypertension (OR=2.71; IC 95%=1.06 - 6.96) and more frequently lacunae associated with WML (OR=4.48; IC 95%=1.18 - 16.99). Subjects with WML had significantly poorer cognitive functions than those without WML (CEP score/100=62.33 +/- 13.58 versus 71.87 +/- 14.19, p<0.01 and MMSE score/30=27.02 +/- 2.34 versus 27.97 +/- 1.89, p<0.01) CONCLUSION: Our results showed a relationship between WML on CT brain scan and the depth of cognitive dysfunction among MCI patients. Further long term prospective studies have to be performed to determinate if WML are involved in transitions between MCI and Alzheimer' s disease.","Age Factors;Aged;Brain/*radiography;Brain Infarction/complications/radiography;Cognition Disorders/*complications;Female;Humans;Hypertension/complications;Male;Neuropsychological Tests;Prospective Studies;Tomography, X-Ray Computed","Duron, E.;Alami, A.;Pequignot, R.;Bert, P.;Rigaud, A. S.;Hanon, O.",2007,Aug,,0,
4538,Unihemispheric acute disseminated encephalomyelitis: A case report,"Acute disseminated encephalomyelitis (ADEM) is a rare idiopathic inflammatory demyelinating disease of the central nervous system (CNS), which usually occurs following a viral or bacterial infection, or vaccination. Characteristically, ADEM presents with acute encephalopathy with accompanying multifocal neurological symptoms and signs. Due to unavailability of a specific biological marker, neuroimaging is very important in establishing the diagnosis of ADEM. The typical magnetic resonance imaging findings of ADEM are large, multiple and almost symmetrical white matter lesions. Herein, we report a 31-year-old woman presenting with headache, confusion, left hemiparesis and hemihypoesthesia preceded by an infection. The patient fully recovered after intravenous methylprednisolone treatment. MRI revealed white-matter lesions that were typical for ADEM, but the unihemispheric involvment broadened the spectrum of disseminated encephalomyelitis. © Archives of Neuropsychiatry.",,"Durmuş, H.;Türkoǧlu, R.;Tüzün, E.",2010,2010,,0,
4539,Inobvious stroke: a cause of delirium and dementia,"Six hundred and sixty-one patients with stroke, confirmed by CT scan or at autopsy, were reviewed in order to evaluate the frequency of presentation with altered mental state. Nineteen patients (3%) had presented with delirium, an organic delusional state, the acute onset of dementia, or mania, mimicking psychiatric illness. All had focal cerebrovascular lesions which were usually, but not invariably, right sided. None had a previous history of cognitive impairment, psychiatric disease, drug abuse, or alcohol excess. Neurological signs were absent or mild and transient, and therefore easily missed. Post-mortem examinations in four patients showed localised cerebral infarctions with no evidence of multiple lesions, Alzheimer's disease, or metabolic encephalopathies. The possible causative factors are discussed and the evidence of asymmetrical cerebral representation of emotion, and for a relationship with epilepsy, is reviewed.","Adult;Aged;Cerebrovascular Disorders/*complications/diagnosis/psychology;Delirium/diagnosis/*etiology;Dementia/diagnosis/*etiology;Diagnosis, Differential;Female;Humans;Male;Middle Aged;Neurocognitive Disorders/diagnosis/*etiology","Dunne, J. W.;Leedman, P. J.;Edis, R. H.",1986,Dec,,0,
4540,Pattern and progression of white-matter changes in a case of posterior cortical atrophy using diffusion tensor imaging,"Background:The progression of white-matter changes in a case of posterior cortical atrophy (PCA) was examined over a period of 15 months using diffusion tensor imaging (DTI) and the association with neuropsychological variables was studied. Patient and methods:A PCA patient was observed over a period of 15 months. DTI and volumetric magnetic resonance imaging were obtained at visit 1 and 15 months later. Fractional anisotropy (FA) and volumetric changes were compared with findings in a typical case of Alzheimer disease (AD) and in 65 healthy volunteers, and the association of neuropsychological deficits with these changes was studied. Results:Reduction in FA was focused on the occipital lobe in the early stages of PCA. During the 15-month period, the FA values of the PCA patient tended to align with the FA ratios of the AD patient, with a more pronounced",,"Duning, T.;Warnecke, T.;Mohammadi, S.;Lohmann, H.;Schiffbauer, H.;Kugel, H.;Knecht, S.;Ringelstein, E. B.;Deppe, M.",2009,April,,0,
4541,Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism,"BACKGROUND AND PURPOSE: Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism. MATERIALS AND METHODS: Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls. RESULTS: Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (rho = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (rho = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (rho = -0.51, P = .0003). CONCLUSIONS: In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.","Basal Ganglia/pathology/ physiopathology;Brain/pathology/ physiopathology;Cognitive Dysfunction/etiology/ physiopathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neural Pathways/pathology/ physiopathology;Parkinson Disease, Secondary/complications/pathology/ physiopathology","Dunet, V.;Deverdun, J.;Charroud, C.;Le Bars, E.;Molino, F.;Menjot de Champfleur, S.;Maury, F.;Charif, M.;Ayrignac, X.;Labauge, P.;Castelnovo, G.;Pinna, F.;Bonafe, A.;Geny, C.;Menjot de Champfleur, N.",2016,Dec,,0,4542
4542,Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism,"BACKGROUND AND PURPOSE: Patients with vascular parkinsonism have higher cognitive decline and more basal ganglia lesions. We aimed to evaluate the relationship of cognitive impairment with functional connectivity between the basal ganglia and cingulate cortex in vascular parkinsonism. MATERIALS AND METHODS: Thirty patients (8 with vascular parkinsonism and 22 with Parkinson disease) and 23 controls were enrolled. The Mattis Dementia Rating Scale and the Stroop Task were used to assess cognitive decline. MR imaging examinations included T1-MPRAGE, FLAIR, and resting-state fMRI sequences. MPRAGE was segmented to obtain basal ganglia and cingulate cortex volumes. FLAIR was segmented to obtain white matter hyperintensity lesion volume. Resting-state fMRI sequences were used to compare basal ganglia functional connectivity with the cingulate cortex between patients and controls. RESULTS: Patients with vascular parkinsonism exhibited impaired attention, resistance to interference, and inhibitory control and an increased number of errors on the Stroop Task. They also had higher caudate nucleus and white matter hyperintensity lesion volumes, which were positively correlated (rho = 0.75, P < .0001). Caudate nucleus functional connectivity with the perigenual anterior cingulate cortex was increased in patients with vascular parkinsonism compared with controls and patients with Parkinson disease, and it was positively correlated with the caudate nucleus volume (rho = 0.44, P = .016). Caudate nucleus functional connectivity with the posterior cingulate cortex was decreased in patients with vascular parkinsonism compared with controls and negatively correlated with the number of errors on the Stroop test (rho = -0.51, P = .0003). CONCLUSIONS: In patients with vascular parkinsonism, cognitive decline could be related to changes of caudate nucleus functional connectivity with the cingulate cortex at resting-state, which may be induced by ischemia-related remodelling.",,"Dunet, V.;Deverdun, J.;Charroud, C.;Le Bars, E.;Molino, F.;Menjot de Champfleur, S.;Maury, F.;Charif, M.;Ayrignac, X.;Labauge, P.;Castelnovo, G.;Pinna, F.;Bonafe, A.;Geny, C.;Menjot de Champfleur, N.",2016,Jul 14,10.3174/ajnr.A4889,0,
4543,Polyarticular juvenile idiopathic arthritis associated with Fahr's syndrome,"Bilateral symmetric calcification involving striatum pallidum with or without deposits in the dentate nucleus, thalamus and white matter is commonly referred to as Fahr's syndrome. Symptoms of the disorder may include deterioration of motor function, spasticity, spastic paralysis, dysarthria, dementia, seizures, headache and athetosis. The clinical and imaging abnormalities are restricted to the central nervous system (CNS). We report an unusual association of Fahr's syndrome with polyarticular juvenile idiopathic arthritis in a girl.",,"Dundar, U.;Solak, O.;Yigit, I.;Kavuncu, V.",2007,1,,0,
4544,Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease?,"BACKGROUND: The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging. METHODS: Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics. RESULTS: Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P = 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects. CONCLUSIONS: At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD. (c) 2015 International Parkinson and Movement Disorder Society.",,"Duncan, G. W.;Firbank, M. J.;Yarnall, A. J.;Khoo, T. K.;Brooks, D. J.;Barker, R. A.;Burn, D. J.;O'Brien, J. T.",2016,Jan,10.1002/mds.26312,0,
4545,Magnetic resonance imaging: A biomarker for cognitive impairment in Parkinson's disease?,"Dementia is a frequent and disabling complication of Parkinson's disease (PD). Clinicians and researchers lack a biomarker capable of tracking the structural and functional changes that underlie the evolution of cognitive dysfunction in PD. Magnetic resonance imaging (MRI) has been adopted as a biomarker in natural history and interventional studies of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), but its utility as a biomarker for PD and Parkinson's disease dementia (PDD) is unclear. In this review, the authors summarize the studies that have used MRI to investigate cognitive decline in PD, outline limitations of those studies, and suggest directions for future research. PD dementia is associated with extensive cortical atrophy, which may be quantified with structural MRI. More promisingly, patterns of atrophy may be present in those who have PD with MCI (PD-MCI). Subcortical white matter tract degeneration is detectable early in the disease with diffusion tensor imaging and may precede changes observed on conventional structural MRI. Although less well studied, other",,"Duncan, G. W.;Firbank, M. J.;O'Brien, J. T.;Burn, D. J.",2013,April,,0,
4546,Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington's disease,"OBJECTIVES: To investigate the function-structure relationship of white matter within different stages of Huntington's disease (HD) using diffusion tensor imaging (DTI). EXPERIMENTAL DESIGN: From the TRACK-HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age-matched to two healthy control groups; all underwent 3-T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. PRINCIPLE OBSERVATIONS: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 - P < 0.005), sensorimotor (P < 0.01 - P < 0.005), and prefrontal region (P < 0.01). CONCLUSIONS: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks.","Adult;Brain/pathology;Brain Mapping;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Huntington Disease/ pathology/psychology;Male;Middle Aged;Motor Cortex/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Dumas, E. M.;van den Bogaard, S. J.;Ruber, M. E.;Reilman, R. R.;Stout, J. C.;Craufurd, D.;Hicks, S. L.;Kennard, C.;Tabrizi, S. J.;van Buchem, M. A.;van der Grond, J.;Roos, R. A.",2012,Jan,10.1002/hbm.21205,0,
4547,Unusual clinical cases that mimic acute disseminated encephalomyelitis,"Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically.",,"Duman, Ö;Yürekli, V. A.;Gencpinar, P.;Karaali, K.;Gümüş, H.;Okuyaz, Ç;Hazar, V.;Haspolat, Ş",2015,2015,,0,
4548,Grey matter correlates of susceptibility to scams in community-dwelling older adults,"Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.","Age Factors;Aged;Aged, 80 and over;Aging;Brain/pathology;Cognition/ physiology;Cognition Disorders/psychology;Cohort Studies;Decision Making/physiology;Female;Frontal Lobe/pathology;Gray Matter/ pathology;Humans;Male;Neuropsychological Tests;Self Report;Temporal Lobe/pathology;Vulnerable Populations/psychology;White Matter/physiology;Brain volumetry;Cognition;Hippocampus;Parahippocampus;Scam","Duke Han, S.;Boyle, P. A.;Yu, L.;Arfanakis, K.;James, B. D.;Fleischman, D. A.;Bennett, D. A.",2016,Jun,,0,4549
4549,Grey matter correlates of susceptibility to scams in community-dwelling older adults,"Susceptibility to scams is a significant issue among older adults, even among those with intact cognition. Age-related changes in brain macrostructure may be associated with susceptibility to scams; however, this has yet to be explored. Based on previous work implicating frontal and temporal lobe functioning as important in decision making, we tested the hypothesis that susceptibility to scams is associated with smaller grey matter volume in frontal and temporal lobe regions in a large community-dwelling cohort of non-demented older adults. Participants (N = 327, mean age = 81.55, mean education = 15.30, 78.9 % female) completed a self-report measure used to assess susceptibility to scams and an MRI brain scan. Results indicated an inverse association between overall grey matter and susceptibility to scams in models adjusted for age, education, and sex; and in models further adjusted for cognitive function. No significant associations were observed for white matter, cerebrospinal fluid, or total brain volume. Models adjusted for age, education, and sex revealed seven clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, left middle temporal, left orbitofrontal, right ventromedial prefrontal, right middle temporal, right precuneus, and right dorsolateral prefrontal regions. In models further adjusted for cognitive function, results revealed three significant clusters showing smaller grey matter in the right parahippocampal/hippocampal/fusiform, right hippocampal, and right middle temporal regions. Lower grey matter concentration in specific brain regions may be associated with susceptibility to scams, even after adjusting for cognitive ability. Future research is needed to determine whether grey matter reductions in these regions may be a biomarker for susceptibility to scams in old age.",,"Duke Han, S.;Boyle, P. A.;Yu, L.;Arfanakis, K.;James, B. D.;Fleischman, D. A.;Bennett, D. A.",2015,Jun 23,10.1007/s11682-015-9422-4,0,
4550,Matrix Metalloproteinases in Alzheimer's Disease and Concurrent Cerebral Microbleeds,"Matrix metalloproteinases (MMPs) are a family of enzymes able to degrade components of the extracellular matrix, which is important for normal blood-brain barrier function. Their function is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). We investigated whether MMPs and TIMPs in cerebrospinal fluid (CSF) and plasma were altered in Alzheimer's disease (AD) and vascular dementia (VaD), and whether this effect was modified by presence of cerebral micro-bleeds in AD patients. In addition, we assessed associations of MMPs and TIMPs with CSF amyloid-beta(1-42) (Abeta42), tau, and tau phosphorylated at threonine-181 (p-tau). We measured MMP2, MMP9, and MMP10, and TIMP1 and TIMP2 in CSF and plasma of 52 AD patients, 26 matched controls, and 24 VaD patients. AD patients showed higher plasma MMP2 levels compared to VaD patients (p < 0.05), and higher CSF MMP10 levels compared to controls (p < 0.05). Microbleeds in AD were associated with lower CSF TIMP1, TIMP2 and MMP9 in a dose-response relation. In addition, CSF MMP2 was associated with p-tau (St.B 0.23, p < 0.05), and CSF MMP10 with tau (St.B 0.38, p < 0.001) and p-tau (St.B 0.40, p < 0.001). Our findings suggest involvement of MMP2 and MMP10 in AD pathology. Lower levels of TIMPs in AD patients with microbleeds suggest less MMP inhibition in patients with concurrent cerebral microbleeds, which may hypothetically lead to a more vulnerable blood-brain barrier in these patients.",Aged;Alzheimer Disease/pathology/*physiopathology;Amyloid beta-Peptides/cerebrospinal fluid;Biomarkers/cerebrospinal fluid;Blood Chemical Analysis;Brain/pathology/*physiopathology;Cerebral Hemorrhage/pathology/*physiopathology;Enzyme-Linked Immunosorbent Assay;Female;Humans;Magnetic Resonance Imaging;Male;Matrix Metalloproteinases/*blood/*cerebrospinal fluid;Peptide Fragments/cerebrospinal fluid;Phosphorylation;Tissue Inhibitor of Metalloproteinases/blood/cerebrospinal fluid;tau Proteins/cerebrospinal fluid;Alzheimer's disease;cerebral amyloid angiopathy;cerebrospinal fluid;matrix metalloproteinases;microbleeds;tissue inhibitors of matrix metalloproteinases,"Duits, F. H.;Hernandez-Guillamon, M.;Montaner, J.;Goos, J. D.;Montanola, A.;Wattjes, M. P.;Barkhof, F.;Scheltens, P.;Teunissen, C. E.;van der Flier, W. M.",2015,,10.3233/jad-143186,0,
4551,Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates,"Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD. © 2013 by the American Association of Neuropathologists,Inc.",,"Dugger, B. N.;Clark, C. M.;Serrano, G.;Mariner, M.;Bedell, B. J.;Coleman, R. E.;Doraiswamy, P. M.;Lu, M.;Fleisher, A. S.;Reiman, E. M.;Sabbagh, M. N.;Sadowsky, C. H.;Schneider, J. A.;Zehntner, S. P.;Carpenter, A. P.;Joshi, A. D.;Mintun, M. A.;Pontecorvo, M. J.;Skovronsky, D. M.;Sue, L. I.;Beach, T. G.",2014,January,,0,
4552,Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history,"BACKGROUND AND PURPOSE: Cerebral white matter hyperintensities (WMHs) are believed to be the consequence of small vessel disease, and it is uncertain whether their extent predicts the risk of dementia in patients with vascular disease history. Method- Brain MRI was performed in 226 participants of the PROGRESS study. WMH severity was assessed using a visual rating scale. During follow-up, patients were classified for incident severe cognitive deterioration (including dementia) using standard criteria. RESULTS: Over 4-year follow-up, the incidence of severe cognitive deterioration ranged from 1.1 to 9.1 per 100 person-years in patients with respectively no or severe WMHs at baseline. In multivariable analysis, incident severe cognitive deterioration was associated with baseline severe WMHs (odds ratio=7.7, P<0.005). CONCLUSIONS: Higher WMH load is a strong predictor of dementia and cognitive decline in patients with cerebrovascular disease history.","0 (Angiotensin-Converting Enzyme Inhibitors);Y5GMK36KGY (Perindopril);Aged;Angiotensin-Converting Enzyme Inhibitors/therapeutic use;Brain/ pathology;Cerebrovascular Disorders/ pathology/ psychology;Cognition Disorders/ pathology/ psychology;Dementia/pathology/psychology;Disease Progression;Female;Follow-Up Studies;Humans;Ischemic Attack, Transient/pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Perindopril/therapeutic use;Predictive Value of Tests;Recurrence;Stroke/pathology/psychology","Dufouil, C.;Godin, O.;Chalmers, J.;Coskun, O.;MacMahon, S.;Tzourio-Mazoyer, N.;Bousser, M. G.;Anderson, C.;Mazoyer, B.;Tzourio, C.;Investigators, Progress Mri Substudy",2009,Jun,,0,
4553,Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history,"BACKGROUND AND PURPOSE: Cerebral white matter hyperintensities (WMHs) are believed to be the consequence of small vessel disease, and it is uncertain whether their extent predicts the risk of dementia in patients with vascular disease history. Method- Brain MRI was performed in 226 participants of the PROGRESS study. WMH severity was assessed using a visual rating scale. During follow-up, patients were classified for incident severe cognitive deterioration (including dementia) using standard criteria. RESULTS: Over 4-year follow-up, the incidence of severe cognitive deterioration ranged from 1.1 to 9.1 per 100 person-years in patients with respectively no or severe WMHs at baseline. In multivariable analysis, incident severe cognitive deterioration was associated with baseline severe WMHs (odds ratio=7.7, P<0.005). CONCLUSIONS: Higher WMH load is a strong predictor of dementia and cognitive decline in patients with cerebrovascular disease history.","Angiotensin-Converting Enzyme Inhibitors [therapeutic use];Brain [pathology];Cerebrovascular Disorders [pathology] [psychology];Cognition Disorders [pathology] [psychology];Dementia [pathology] [psychology];Disease Progression;Follow-Up Studies;Ischemic Attack, Transient [pathology] [psychology];Magnetic Resonance Imaging;Neuropsychological Tests;Perindopril [therapeutic use];Predictive Value of Tests;Recurrence;Stroke [pathology] [psychology];Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-stroke","Dufouil, C.;Godin, O.;Chalmers, J.;Coskun, O.;MacMahon, S.;Tzourio-Mazoyer, N.;Bousser, M. G.;Anderson, C.;Mazoyer, B.;Tzourio, C.",2009,,10.1161/strokeaha.108.540633,0,
4554,Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort,"BACKGROUND: The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. METHODS: In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral (18)F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions. RESULTS: The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E epsilon4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers worsened with age, whereas differences were not consistent according to sex. CONCLUSIONS: MEMENTO is a large cohort with extensive clinical, neuropsychological and neuroimaging data and represents a platform for studying the natural history of ADRD in a large group of participants with different subtypes of MCI (amnestic or not amnestic) or isolated SCCs. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.",Alzheimer's disease;Cognitive aging;Cohort studies;Natural history studies (prognosis);Neuroimaging,"Dufouil, C.;Dubois, B.;Vellas, B.;Pasquier, F.;Blanc, F.;Hugon, J.;Hanon, O.;Dartigues, J. F.;Harston, S.;Gabelle, A.;Ceccaldi, M.;Beauchet, O.;Krolak-Salmon, P.;David, R.;Rouaud, O.;Godefroy, O.;Belin, C.;Rouch, I.;Auguste, N.;Wallon, D.;Benetos, A.;Pariente, J.;Paccalin, M.;Moreaud, O.;Hommet, C.;Sellal, F.;Boutoleau-Bretonniere, C.;Jalenques, I.;Gentric, A.;Vandel, P.;Azouani, C.;Fillon, L.;Fischer, C.;Savarieau, H.;Operto, G.;Bertin, H.;Chupin, M.;Bouteloup, V.;Habert, M. O.;Mangin, J. F.;Chene, G.;Group, Memento cohort Study",2017,Aug 29,,0,
4555,"Homocysteine, white matter hyperintensities, and cognition in healthy elderly people","Hyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2-year follow-up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross-sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8-fold (p < 0.05) higher in subjects with homocysteine levels above 15 micromol/L compared with those with homocysteine levels below 10 micromol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition.",Aged;Brain/pathology;Cognition;Cognition Disorders/blood/epidemiology/pathology;Cross-Sectional Studies;Dementia/ blood/ epidemiology/pathology;Female;Follow-Up Studies;Homocysteine/ blood;Humans;Hyperhomocysteinemia/ epidemiology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers/pathology;Risk Factors,"Dufouil, C.;Alperovitch, A.;Ducros, V.;Tzourio, C.",2003,Feb,10.1002/ana.10440,0,
4556,Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL,"Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and cognitive symptoms, thus leaving much of the variance in cognitive performance unexplained. The objective of the current study was to investigate the relationship between the location of subcortical ischaemic lesions and cognitive symptoms in small vessel disease. We applied a voxel-based lesion-symptom mapping approach to data from 215 patients with CADASIL, a genetically defined small vessel disease with mutations in the NOTCH3 gene. All patients were examined by magnetic resonance imaging and comprehensive neuropsychological testing. Lacunar lesions and white matter lesions were segmented on three-dimensional T(1) and fluid-attenuated inversion recovery sequences, respectively. One hundred and forty-five subjects had a total of 854 lacunar lesions (range 1-13 per individual). The normalized volume of white matter hyperintensities ranged from 0.0425% to 21.5% of the intracranial cavity. Significant clusters for cognitive performance were detected for both lacunar lesions and white matter hyperintensities. The most prominent results were obtained on a compound score for processing speed, the predominantly affected cognitive domain in this group of patients. Strategic locations included the anterior parts of the thalamus, the genu and anterior limb of the internal capsule, the anterior corona radiata and the genu of the corpus callosum. By combining the lesion-symptom mapping data with information from a probabilistic white matter atlas we found that the majority of the processing speed clusters projected on the anterior thalamic radiation and the forceps minor. In multivariate models that included demographic parameters, brain atrophy and the volume of ischaemic lesions, regional volumes of lacunar lesions and white matter hyperintensities in the anterior thalamic radiation predicted performance in processing speed tasks, whereas there was no independent contribution of the global volume of ischaemic lesions. These observations emphasize the importance of lesion location for both lacunar and ischaemic white matter lesions. Our findings further highlight the anterior thalamic radiation as a major anatomical structure impacting on processing speed. Together these findings provide strong support for a central role of frontal-subcortical circuits in cerebral small vessel disease and vascular cognitive impairment.","Adult;Brain Mapping;CADASIL/ complications/ pathology;Cognition Disorders/ etiology;Cohort Studies;Female;Frontal Lobe/ pathology;Humans;Imaging, Three-Dimensional/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Regression Analysis","Duering, M.;Zieren, N.;Herve, D.;Jouvent, E.;Reyes, S.;Peters, N.;Pachai, C.;Opherk, C.;Chabriat, H.;Dichgans, M.",2011,Aug,10.1093/brain/awr169,0,
4557,Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts,"Objective: To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts. Methods: Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. Results: We found focal cortical thinning specifically in areas connected to acute infarcts (p < 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (ρ -0.39, p 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter. Conclusions: These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke.",adult;aged;article;brain degeneration;brain infarction;brain ischemia;clinical article;clinical assessment;cortical thickness (brain);diffusion tensor imaging;female;human;imaging software;longitudinal study;male;multimodal imaging;National Institutes of Health Stroke Scale;nuclear magnetic resonance imaging;priority journal;prospective study;very elderly;white matter,"Duering, M.;Righart, R.;Wollenweber, F. A.;Zietemann, V.;Gesierich, B.;Dichgans, M.",2015,,,0,
4558,Incident subcortical infarcts induce focal thinning in connected cortical regions,"OBJECTIVE: Brain atrophy is common in subcortical ischemic vascular disease, but the underlying mechanisms are poorly understood. We set out to examine the effects of incident subcortical infarcts on cortical morphology. METHODS: A total of 276 subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, an inherited small vessel disease, were enrolled in a prospective study. Incident subcortical infarcts were identified on follow-up magnetic resonance scans after 18, 36, and 54 months using difference images. Probabilistic fiber tracking and cortical thickness measurements were applied to study the longitudinal relationship between incident infarcts and connected cortical areas. Cortical thickness was assessed before and after infarction using FreeSurfer software. Focal cortical thinning was defined as change of cortical thickness in the connected region of interest exceeding the global change of cortical thickness. RESULTS: Nine subjects had a single incident infarct during the follow-up and were suitable for analysis. There was a strong correlation between the probability of connectivity and mean focal cortical thinning (p = 0.0039). In all subjects, there was focal cortical thinning in cortical regions with high probability of connectivity with the incident infarct. This pattern was not observed when using control tractography seeds. CONCLUSIONS: Our findings provide in vivo evidence for secondary cortical neurodegeneration after subcortical ischemia as a mechanism for brain atrophy in cerebrovascular disease.","Adult;CADASIL/complications;Cerebral Cortex/blood supply/ pathology;Cerebral Infarction/etiology/ pathology;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Incidence;Leukoencephalopathies/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Oxygen/blood;Prospective Studies;Statistics, Nonparametric;Time Factors","Duering, M.;Righart, R.;Csanadi, E.;Jouvent, E.;Herve, D.;Chabriat, H.;Dichgans, M.",2012,Nov 13,10.1212/WNL.0b013e3182749f39,0,
4559,Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment,"Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in processing speed. This has been attributed to a disruption of frontal-subcortical neuronal circuits by ischemic lesions, but the exact mechanisms and underlying anatomical structures are poorly understood. We set out to identify a strategic brain network for processing speed by applying graph-based data-mining techniques to MRI lesion maps from patients with small vessel disease. We studied 235 patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a probabilistic atlas in standard space we first determined the regional volumes of white matter hyperintensities (WMH) and lacunar lesions (LL) within major white matter tracts. Conditional dependencies between the regional lesion volumes and processing speed were then examined using Bayesian network analysis. Exploratory analysis identified a network of five imaging variables as the best determinant of processing speed. The network included LL in the left anterior thalamic radiation and the left cingulum as well as WMH in the left forceps minor, the left parahippocampal white matter and the left corticospinal tract. Together these variables explained 34% of the total variance in the processing speed score. Structural equation modeling confirmed the findings obtained from the Bayesian models. In summary, using graph-based models we identified a strategic brain network having the highest predictive value for processing speed in our cohort of patients with pure small vessel disease. Our findings confirm and extend previous results showing a role of frontal-subcortical neuronal circuits, in particular dorsolateral prefrontal and cingulate circuits, in VCI.",Adult;Aged;Bayes Theorem;Brain/ pathology/physiopathology;CADASIL/ pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/ pathology/physiopathology;Young Adult,"Duering, M.;Gonik, M.;Malik, R.;Zieren, N.;Reyes, S.;Jouvent, E.;Herve, D.;Gschwendtner, A.;Opherk, C.;Chabriat, H.;Dichgans, M.",2013,Feb 1,10.1016/j.neuroimage.2012.10.084,0,
4560,Strategic white matter tracts for processing speed deficits in age-related small vessel disease,Objective: Cerebral small vessel disease is the most common cause of vascular cognitive impairment and typically manifests with slowed processing speed. We investigated the impact of lesion location on processing speed in age-related small vessel disease. Methods: A total of 584 community-dwelling elderly underwent brainMRI followed by segmentation of white matter hyperintensities. Processing speed was determined by the timed measure of the Trail Making Test part B. The impact of the location of white matter hyperintensities was assessed by voxel-based lesion-symptom mapping and graph-based statistical models on regional lesion volumes in major white matter tracts. Results: Voxel-based lesion-symptom mapping identified multiple voxel clusters where the presence of white matter hyperintensities was associated with slower performance on the TrailMaking Test part B. Clusterswere located bilaterally in the forcepsminor and anterior thalamic radiation. Region of interest- based Bayesian network analyses on lesion volumeswithinmajor whitematter tracts depicted the same tracts as direct predictors for an impaired Trail Making Test part B performance. Conclusions: Our findings highlight damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in age-related small vessel disease. © 2014 American Academy of Neurology.,aged;anterior thalamic radiation;article;cerebrovascular disease;cognitive defect;cognitive processing speed deficit;female;frontal lobe;human;major clinical study;male;nerve projection;nerve tract;neuropsychological test;nuclear magnetic resonance imaging;priority journal;response time;task performance;thalamus;Vienna Test System;Wechsler intelligence scale;white matter lesion;Wisconsin Card Sorting Test,"Duering, M.;Gesierich, B.;Seiler, S.;Pirpamer, L.;Gonik, M.;Hofer, E.;Jouvent, E.;Duchesnay, E.;Chabriat, H.;Ropele, S.;Schmidt, R.;Dichgans, M.",2014,,,0,
4561,Free water determines diffusion alterations and clinical status in cerebral small vessel disease,"INTRODUCTION: Diffusion tensor imaging detects early tissue alterations in Alzheimer's disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown. METHODS: To gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, n = 57), sporadic SVD (n = 444), and healthy controls (n = 28). We modeled freely diffusing water in the extracellular space (FW) and measures reflecting fiber structure (tissue compartment). We tested associations between these measures and clinical status (processing speed and disability). RESULTS: Diffusion alterations in SVD were mostly driven by increased FW and less by tissue compartment alterations. Among imaging markers, FW showed the strongest association with clinical status (R(2) up to 34%, P < .0001). Findings were consistent across patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy and sporadic SVD. CONCLUSIONS: Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.",Brain atrophy;Diffusion tensor imaging;Disability;Free water;Lacunes;Processing speed;Small vessel disease;Structural imaging;Vascular cognitive impairment;White matter hyperintensities,"Duering, M.;Finsterwalder, S.;Baykara, E.;Tuladhar, A. M.;Gesierich, B.;Konieczny, M. J.;Malik, R.;Franzmeier, N.;Ewers, M.;Jouvent, E.;Biessels, G. J.;Schmidt, R.;de Leeuw, F. E.;Pasternak, O.;Dichgans, M.",2018,Feb 1,,0,
4562,Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease,"White matter hyperintensities and lacunes are among the most frequent abnormalities on brain magnetic resonance imaging. They are commonly related to cerebral small vessel disease and associated with both stroke and dementia. We examined the spatial relationships between incident lacunes and white matter hyperintensities and related these findings to information on vascular anatomy to study possible mechanistic links between the two lesion types. Two hundred and seventy-six patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetically defined small vessel disease with mutations in the NOTCH3 gene were followed with magnetic resonance imaging over a total of 633 patient years. Using difference images and Jacobian maps from registered images we identified 104 incident lacunes. The majority (n = 95; 91.3%) of lacunes developed at the edge of a white matter hyperintensity whereas few lacunes were found to develop fully within (n = 6; 5.8%) or outside (n = 3; 2.9%) white matter hyperintensities. Adding information on vascular anatomy revealed that the majority of incident lacunes developed proximal to a white matter hyperintensity along the course of perforating vessels supplying the respective brain region. We further studied the spatial relationship between prevalent lacunes and white matter hyperintensities both in 365 patients with CADASIL and in 588 elderly subjects from the Austrian Stroke Prevention Study. The results were consistent with the results for incident lacunes. Lesion prevalence maps in different disease stages showed a spread of lesions towards subcortical regions in both cohorts. Our findings suggest that the mechanisms of lacunes and white matter hyperintensities are intimately connected and identify the edge of white matter hyperintensities as a predilection site for lacunes. Our observations further support and refine the concept of the white matter hyperintensity penumbra.","Adult;Aged;CADASIL/ complications/epidemiology;Cohort Studies;Disease Progression;Female;Humans;Leukoencephalopathies/ epidemiology/ etiology/genetics;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Receptors, Notch/genetics;Stroke, Lacunar/ epidemiology/ etiology/pathology;Young Adult","Duering, M.;Csanadi, E.;Gesierich, B.;Jouvent, E.;Herve, D.;Seiler, S.;Belaroussi, B.;Ropele, S.;Schmidt, R.;Chabriat, H.;Dichgans, M.",2013,Sep,10.1093/brain/awt184,0,
4563,Acute Headache Followed by Focal Neuropsychological Impairment in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL),"Occasionally, patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) present atypical features such as confusion, coma, or nonconvulsive status epilepticus. Acute focal neuropsychological syndrome revealing the disease has been poorly documented. We report the atypical presentation of two patients in whom CADASIL was revealed by an episode of headache followed by focal neuropsychological impairment. © 2010 National Stroke Association.",acute disease;adult;article;CADASIL;case report;gene mutation;genotype;headache;hemianopia;human;male;memory disorder;nuclear magnetic resonance imaging;priority journal;recall;recognition,"Ducray, F.;Ritzenthaler, T.;Cho, T. H.;Bruyas, A.;Cotton, F.;Cartalat-Carel, S.;Honnorat, J.;Nighoghossian, N.",2010,,,0,
4564,MRI-based automated computer classification of probable AD versus normal controls,"Automated computer classification (ACC) techniques are needed to facilitate physician's diagnosis of complex diseases in individual patients. We provide an example of ACC using computational techniques within the context of cross-sectional analysis of magnetic resonance images (MRI) in neurodegenerative diseases, namely Alzheimer's dementia (AD). In this paper, the accuracy of our ACC methodology is assessed when presented with real life, imperfect data, i.e., cohorts of MRI with varying acquisition parameters and imaging quality. The comparative methodology uses the Jacobian determinants derived from dense deformation fields and scaled grey-level intensity from a selected volume of interest centered on the medial temporal lobe. The ACC performance is assessed in a series of leave-one-out experiments aimed at separating 75 probable AD and 75 age-matched normal controls. The resulting accuracy is 92% using a support vector machine classifier based on least squares optimization. Finally, it is shown in the Appendix that determinants and scaled grey-level intensity are appreciably more robust to varying parameters in validation studies using simulated data, when compared to raw intensities or grey/white matter volumes. The ability of cross-sectional MRI at detecting probable AD with high accuracy could have profound implications in the management of suspected AD candidates.","Adult;Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/ diagnosis;Artificial Intelligence;Brain/ pathology;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Pattern Recognition, Automated/ methods;Reference Values;Reproducibility of Results;Sensitivity and Specificity","Duchesne, S.;Caroli, A.;Geroldi, C.;Barillot, C.;Frisoni, G. B.;Collins, D. L.",2008,Apr,10.1109/tmi.2007.908685,0,
4565,Does a positive pittsburgh compound b scan in a patient with dementia equal alzheimer disease?,"Importance The clinical role of amyloid brain positron emission tomographic imaging in the diagnosis of Alzheimer disease is currently being formulated. The specificity of a positive amyloid scan is a matter of contention. OBSERVATIONS An 83-year-old Canadian man presented with a 5-year history of predominantly short-term memory loss and functional impairment. Clinical evaluation revealed significant, gradually progressive short-term memory loss in the absence of any history of strokes or other neuropsychiatric symptoms. The patient met clinical criteria for probable Alzheimer disease but had a higher than expected burden of white matter disease on magnetic resonance imaging. A positron emission tomographic Pittsburgh Compound B scan was highly positive in typical Alzheimer disease distribution. The patient died of an intracerebral hemorrhage 6 months after the assessment. Autopsy revealed cerebral amyloid angiopathy in the complete absence of amyloid plaques or neurofibrillary tangles. CONCLUSIONS AND RELEVANCE This patient demonstrates that a positive Pittsburgh Compound B scan in a patient with clinical dementia meeting criteria for probable Alzheimer disease is not proof of an Alzheimer disease pathophysiological process. A positive Pittsburgh Compound B scan in typical Alzheimer disease distribution in a patient with dementia can be secondary to cerebral amyloid angiopathy alone.",,"Ducharme, S.;Guiot, M. C.;Nikelski, J.;Chertkow, H.",2013,July,,0,
4566,Progressive supranuclear palsy and a multi-infarct state,"In 58 patients with progressive supranuclear palsy (PSP), 19 (32.8%) had CT, MRI, or autopsy evidence of a multi-infarct (MI) state. The clinical findings in the infarct syndrome were similar to idiopathic PSP. Five MI-PSP patients had had a stroke, four had focal dystonia, two had hemiparesis, and one had an intention tremor of recent onset. In contrast, only 5.9% (12.9% of those with CT or MRI) of 426 Parkinson's disease patients had evidence of strokes. One case of PSP studied pathologically was attributed to cerebral amyloid angiopathy.",amyloidosis;autopsy;central nervous system;cerebrovascular disease;clinical article;computer analysis;computer assisted tomography;diagnosis;dystonia;hemiparesis;histology;human;multiinfarct dementia;nervous system;peripheral vascular system;priority journal;progressive supranuclear palsy;cerebrovascular accident,"Dubinsky, R. M.;Jankovic, J.",1987,,,0,
4567,Sensitivity and specificity of positron emission tomography and magnetic resonance imaging studies in Alzheimer's disease and multi-infarct dementia,"Positron emission tomographic (PET) scans using [18F]-fluorodeoxyglucose and magnetic resonance imaging (MRI) scans were quantitatively analyzed for metabolic and structural abnormalities in normal subjects and patients classified as having Alzheimer's disease (AD), mixed dementia and multi-infarct dementia (MID) according to Hachinski ischemic scores. MRI-detected abnormalities in the periventricular white matter and in subcortical locations increased in incidence with age in normals and increased markedly in AD and especially in MID. Upper limits for the severity of these white matter lesions could be defined only for normal young and elderly subjects, but not for AD, mixed or MID patients. PET scan abnormalities occurred in about 90% of demented patients and in 54% of elderly and 34% of young normals. There was no characteristic pattern of abnormality that distinguished MID from AD patients. It is concluded that PET and MRI studies in demented patients are useful ancillary tests especially in evaluating the mild, questionably demented subject and for assessing the functional impact of structural disease.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/metabolism/ radionuclide imaging;Dementia, Multi-Infarct/diagnosis/metabolism/ radionuclide imaging;Deoxyglucose/analogs & derivatives/pharmacokinetics;Fluorodeoxyglucose F18;Humans;Magnetic Resonance Imaging;Middle Aged","Duara, R.;Barker, W.;Loewenstein, D.;Pascal, S.;Bowen, B.",1989,,,0,
4568,Acute diffusion-weighted imaging lesion patterns predict progressive small subcortical infarct in the perforator territory of the middle cerebral artery,"Background: Single small subcortical infarct (SSSI) is generally considered to have a fair outcome. However, early neurological deterioration (END), a relatively unfavorable clinical course occurring during the acute phase of infarction, is not uncommon. Aims: The aim of this study was to investigate the relationship between lesion patterns detected by diffusion-weighted imaging (DWI) and the presence of END in patients with acute SSSI in the perforator territory of the middle cerebral artery (MCA). Methods: Three hundred twelve patients with acute SSSI in the perforator territory of MCA were prospectively recruited from Jinling Hospital between January 2010 and May 2013. Acute DWI lesion patterns were classified as proximal SSSI (pSSSI) or distal SSSI (dSSSI) patterns, according to the relationship between lesion location and the parent artery. Neurological deficits were evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and continued over the following 72h 1-3 times a day. END was defined as an increase in NIHSS score ≥2 points during the first 72h after admission. Results: Of the total 312 patients, the pSSSI pattern was found in 139 (44·55%) patients and the dSSSI pattern in 173 (55·45%) patients. Statistical analysis suggested that the indicators for small-artery disease (hypertension and leukoaraiosis) and atherosclerosis (diabetes mellitus and cerebral atherosclerosis) significantly differed according to lesion patterns (P<0·05). During hospitalization, 88 (28·21%) patients experienced END. Univariate analysis revealed that female sex (P=0·004), pSSSI pattern (P<0·001), initial NIHSS (P=0·001), lesion diameter (P=0·005), ipsilateral large-artery stenosis (P=0·008), and concomitant intracranial atherosclerotic stenosis (P=0·021) were significantly associated with END. After adjusting for confounding factors, pSSSI pattern was an independent predictor of END (OR 1·871, 95% CI 1·095-3·198, P=0·022). In the further subgroup analysis of patients with different etiologies, pSSSI pattern was found to be independently associated with END in patients with large-artery atherosclerosis (OR 3·593, 95% CI 1·268-11·057, P=0·026) and in patients with small-artery disease (OR 2·523, 95% CI 1·121-5·676, P=0·025), but not in patients with cardioembolism (OR 0·854, 95% CI 0·147-4·953, P=0·861). Conclusions: pSSSI pattern was closely related to END in acute SSSI caused by large-artery atherosclerosis and small-artery disease in the perforator territory of the MCA.",,"Duan, Z.;Sun, W.;Liu, W.;Xiao, L.;Huang, Z.;Cao, L.;Li, H.;Xiong, Y.;Liu, D.;Xu, G.;Liu, X.",2015,1,,0,
4569,White matter damage of patients with Alzheimer's disease correlated with the decreased cognitive function,"Increasing evidence demonstrates that there is marked damage and dysfunction in the white matter in Alzheimer's disease (AD). The present study investigates the nature of white matter damage of patients with Alzheimer's disease with diffusion tensor magnetic resonance imaging (DTI) and analyses the relationship between the white matter damage and the cognition function. DTI, as well as T1 fluid attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable patients of Alzheimer's disease, and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, and the white matter of frontal, temporal, parietal, and occipital lobes. FA was lower in the splenium of corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding region from healthy controls and was strongly positive correlated with MMSE scores, whereas FA appeared no different in the anterior and posterior limbs of internal capsule, occipital lobes white matter, and the genu of corpus callosum between the patients and healthy controls. MD was significantly higher in the splenium of corpus callosum and parietal lobes white matter from patients than in that those from healthy controls and was strongly negative correlated with MMSE scores, whereas MD in the anterior and posterior limbs of internal capsule, as well as in frontal, temporal, occipital lobes white matter and the genu of corpus callosum, was not different between the patients and healthy controls. The most prominent alteration of FA and MD was in the splenium of corpus callosum. Our results suggested that white matter of patients with Alzheimer's disease was selectively impaired and the extent of damage had a strong correlation with the cognitive function, and that selective impairment reflected the cortico-cortical and cortico-subcortical disconnections in the pathomechanism of Alzheimer's disease. The values of FA and MD in white matter, especially in the splenium of corpus callosum in AD patients, might be a more appropriate surrogate marker for monitoring the disease progression.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ diagnosis;Anisotropy;Brain/ pathology;China;Cognition Disorders/complications/ diagnosis;Corpus Callosum/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Disease Progression;Female;Humans;Image Processing, Computer-Assisted/methods;Male;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Reference Values","Duan, J. H.;Wang, H. Q.;Xu, J.;Lin, X.;Chen, S. Q.;Kang, Z.;Yao, Z. B.",2006,May,10.1007/s00276-006-0111-2,0,
4570,Correlation between white matter damage and cognitive function in patients with Alzheimer's disease,"Objective: To investigate the nature of white matter damage and its correlation to the cognition function in patients with Alzheimer's disease (AD) by using the diffusion tensor imaging (DTI). Methods: Diffusion tensor imaging, as well as T(1)-fluid attenuated inversion recovery (FLAIR) and T (2)-FLAIR, was performed in probable AD patients and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule and the white matter of the frontal, temporal, parietal and occipital lobes. Correlation analysis was applied to reveal the relationship between the FA and MD values and the MMSE scores. Results: In contrast to healthy controls, patients with AD have a lower FA in the splenium of corpus callosum (0.602 ± 0.043), as well as in the white matter of the frontal (0.270 ± 0.034), temporal (0.302 ± 0.032), and parietal lobes (0.294 ± 0.043). Besides, FA of AD patients was also strongly positive correlated with MMSE scores, but there was no difference in FA between AD patients and controls in the anterior and posterior limbs of internal capsule, occipital lobes white matter and the genu of corpus callosum. While in comparison with that of healthy controls, MD of AD patients was significantly higher in the splenium of corpus callosum ((0.918 ± 0.029) × 10(-9) m(2)/s) and parietal lobes white matter ((0.826 ± 0.015) × 10(-9) m(2)/s) and was strongly negative correlated with MMSE scores, but there was no difference in MD between AD patients and controls in the anterior and posterior limbs of internal capsule, as well as in frontal, temporal, occipital lobes white matter and the genu of corpus callosum. Conclusion: The white matter of patients with AD should be selectively impaired and the extent of damage should have a strong correlation with the cognition function. The selective impairment might reflect the cortico-cortical and cortico-subcortical disconnections in the pathomechanism of AD. DTI technique might be used to monitor the disease progression and as a surrogate marker for evaluation of drug efficacy in vivo.",,"Duan, J. H.;Wang, H. Q.;Chen, S. Q.;Xu, J.;Lin, X.;Kang, Z.;Yao, Z. B.",2006,23,,0,
4571,"Characteristics of clinical presentation, neuroimaging and genetics in a patient with logopenic variant primary progressive aphasia","Objective: To discuss the characteristics of clinical presentation, neuroimaging and genetics in a patient with logopenic variant primary progressive aphasia (IvPPA). Methods: A case of IvPPA diagnosed with clinical presentation, neuropsychological tests, neuroimaging and genetic testing was reported, and the clinical characteristics of IvPPA were summarized. Results: The initial symptom of IvPPA was progressive language impairment. A series of neuropsychological tests showed impaired spontaneous naming, repetition and intelligence with normal daily life ability and mental behavior. Neuroimaging examination showed multiple atrophy and hypo-perfusion in left frontal lobe, temporo-parietal lobe, lateral fissure and hippocampus. Moreover, high signal was revealed in left atrophic frontal subcortical white matter regions on FLAIR, which was normal on DWI and susceptibility weighted imaging. MR angiography showed slender left middle cerebral artery with sparse branches in distal, and 18F-fluorodeoxyglucose positron emission tomography showed hypometabolism in left frontal lobe, temporo-parietal lobe and hippocampus. Genetic testing revealed a pathogenic intron splicing mutation c.708+1G>A reported before in progranulin (GRN) gene, and two novel extron hybrid mutations c.241A>C and c.242G>C in gelsolin gene. Conclusions: IvPPA prominently manifested with impaired spontaneous naming and repetition in progressive language disorder, accompanied with slight intelligent impairment. Atrophy and hypoperfusion regions were mainly distributed in left frontal lobe, temporo-parietal lobe, lateral fissure and hippocampus, with involvement of subcortical white matter and slender left middle cerebral artery. Genetic testing for pathogenic mutation in GRN gene was helpful for diagnosis of 1vPPA.",fluorodeoxyglucose f 18;article;brain atrophy;brain perfusion;clinical feature;daily life activity;diffusion weighted imaging;disease course;frontal lobe;gelsolin gene;gene;gene mutation;genetic screening;genetics;hippocampus;human;intelligence;intron;language disability;logopenic variant primary progressive aphasia;magnetic resonance angiography;mental health;middle cerebral artery;neuroimaging;neuropsychological test;parietal lobe;perfusion;positron emission tomography;primary progressive aphasia;progranulin gene;susceptibility weighted imaging;Sylvian fissure;symptom;temporal lobe;white matter lesion,"Du, Y.;Zhao, D.;Ge, F.;Guo, P.;Li, C.;Zhang, M.;Shen, J.;Lu, J.;Li, Z.;Zhang, W.",2016,,,0,
4572,Effects of subcortical ischemic vascular dementia and AD on entorhinal cortex and hippocampus,"OBJECTIVE: To determine the effects of subcortical ischemic vascular dementia (SIVD) and AD on entorhinal cortex (ERC) and hippocampus. METHODS: Thirty-eight cognitively normal subjects, 18 patients with SIVD, and 22 patients with AD were included. Volumes of ERC and hippocampus were manually measured based on MRI. Global cerebral changes of cortical gray matter, subcortical gray matter, white matter, sulcal CSF, ventricular CSF (vCSF), and white matter signal hyperintensities (WMSH) were assessed. RESULTS: Patients with SIVD had 21.7% (p < 0.01) smaller ERC and 18.2% (p < 0.01) smaller hippocampi than cognitively normal subjects and 24.4% (p < 0.01) larger ERC and 11.1% (p < 0.05) larger hippocampi than patients with AD. In addition, patients with SIVD had less cortical gray matter and white matter and more vCSF and WMSH (all p < 0.01) than cognitively normal subjects and more vCSF and WMSH (p < 0.01) than patients with AD. The volumes of ERC and hippocampus were positively correlated to similar extents (p < 0.01) in SIVD and AD. Cortical gray matter loss was positively correlated (p < 0.01) with hippocampal atrophy, but not with ERC atrophy, in SIVD and AD. Hippocampal volume alone could classify 82% of patients with SIVD from cognitively normal subjects and 63% of patients with SIVD from subjects with AD. Adding global cerebral changes to hippocampus substantially improved the classification to 96% between patients with SIVD and cognitively normal subjects and 83% between subjects with SIVD and those with AD, whereas adding ERC change to hippocampus did not significantly improve the discrimination. CONCLUSIONS: The entorhinal cortex and hippocampus are less affected by subcortical ischemic vascular dementia than by AD.","Aged;Alzheimer Disease/*pathology;Brain Ischemia/*pathology;Dementia, Vascular/*pathology;Diagnosis, Differential;Entorhinal Cortex/*pathology;Female;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Sensitivity and Specificity","Du, A. T.;Schuff, N.;Laakso, M. P.;Zhu, X. P.;Jagust, W. J.;Yaffe, K.;Kramer, J. H.;Miller, B. L.;Reed, B. R.;Norman, D.;Chui, H. C.;Weiner, M. W.",2002,Jun 11,,0,
4573,White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy,"The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.","Aged;Aged, 80 and over;Alzheimer Disease/complications/*pathology;Atrophy/pathology;Cerebral Cortex/*pathology;Cognition Disorders/etiology/pathology;Dementia, Vascular/etiology/*pathology;Entorhinal Cortex/*pathology;Female;Hippocampus/*pathology;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests","Du, A. T.;Schuff, N.;Chao, L. L.;Kornak, J.;Ezekiel, F.;Jagust, W. J.;Kramer, J. H.;Reed, B. R.;Miller, B. L.;Norman, D.;Chui, H. C.;Weiner, M. W.",2005,Apr,10.1016/j.neurobiolaging.2004.05.002,0,
4574,Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function,"Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.",Cognitive function;diffusion tensor imaging;small vessel disease;tractography,"D'Souza, M. M.;Gorthi, S. P.;Vadwala, K.;Trivedi, R.;Vijayakumar, C.;Kaur, P.;Khushu, S.",2018,Feb,,0,
4575,Obesity and Structural Brain Integrity in Older Women: The Women's Health Initiative Magnetic Resonance Imaging Study,"BACKGROUND: Midlife obesity has been linked to age-related brain atrophy and risk of dementia, but the relationships are less clear for older individuals. These associations may be explained by changes in appetite or metabolism in the dementia prodrome; thus, prospective studies with adequate follow-up are needed. We examined the associations that obesity (body mass index, BMI) and change in BMI over an average of 6.6 (1.0-9.1) years have with global and regional brain and white matter lesion volumes in a sample of 1,366 women aged 65-80. METHODS: Least square means for regional brain volumes and white matter lesion loads for women grouped by BMI and changes in BMI were generated from multivariable linear models with and without adjustment for demographic and health covariates. RESULTS: Both global obesity and increase in BMI were associated with lower cerebrospinal fluid and higher specific brain volumes (ps < .05), after controlling for diabetes and other cerebrovascular disease risk factors. Obesity, but not change in BMI, predicted lower lesion loads for the total, parietal, and occipital white matter (ps < .05). CONCLUSIONS: Obesity in this cohort is associated with less brain atrophy and lower ischemic lesion loads. The findings are consistent with our previous report of worse cognitive performance in association with weight loss (probably not due to frailty) in this cohort and in line with the idea of the ""obesity paradox"" as differences in dementia risk vary across time, whereby midlife obesity seems to be a predictor of dementia, whereas weight loss seems to be a better predictor at older ages.",,"Driscoll, I.;Gaussoin, S. A.;Wassertheil-Smoller, S.;Limacher, M.;Casanova, R.;Yaffe, K.;Resnick, S. M.;Espeland, M. A.",2016,Mar 9,10.1093/gerona/glw023,0,
4576,Cerebral metabolic and structural alterations in hereditary spastic paraplegia with thin corpus callosum assessed by MRS and DTI,"Introduction: Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a complicated form of autosomal-recessive hereditary spastic paraplegia. Characteristic clinical features comprise progressive spastic gait, cognitive impairment, and ataxia. Diagnostic MRI findings include thinning of the corpus callosum and non-progressive white matter (WM) alterations. Methods: To study the extent of axonal involvement, we performed localized proton magnetic resonance spectroscopy (MRS) of the cerebral WM and cortical grey matter (GM) in a patient with HSP-TCC at 20 and 25 years of age. The second investigation included diffusion tensor imaging (DTI). Results: While MRS of the GM was normal, affected WM was characterized by major metabolic alterations such as reduced concentrations of N-acetylaspartate and N-acetylaspartyl-glutamate, creatine and phosphocreatine, and choline-containing compounds as well as elevated levels of myo-inositol. These abnormalities showed progression over a period of 5 years. DTI revealed increased mean diffusivity as well as reduced fractional anisotropy in periventricular WM. The metabolic and structural findings are consistent with progressive neuroaxonal loss in the WM accompanied by astrocytic proliferation - histopathological changes known to occur in HSP-TCC. Conclusion: Our results are in agreement with the hypothesis that the primary pathological process in HSP-TCC affects the axon, possibly due to impaired axonal trafficking. © Springer-Verlag 2006.",,"Dreha-Kulaczewski, S.;Dechent, P.;Helms, G.;Frahm, J.;Gärtner, J.;Brockmann, K.",2006,December,,0,
4577,Disease tracking markers for Alzheimers Disease at the prodromal (MCI) stage,"Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimers Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross-sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as Aβ1-42, t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimers disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimers disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD. © 2011 IOS Press and the authors. All rights reserved.",amyloid beta protein[1-42];benzodiazepine derivative;cholinesterase inhibitor;isoprostane derivative;psychotropic agent;tau protein;Alzheimer disease;article;brain atrophy;brain region;brain size;brain ventricle;cerebrospinal fluid analysis;cognitive defect;correlation analysis;dementia;disease course;disease marker;disease severity;drug mechanism;electroencephalogram;episodic memory;event related potential;fluency disorder;functional magnetic resonance imaging;hippocampus;human;mild cognitive impairment;neurobiology;neuroimaging;neuropsychology;patient monitoring;predictive validity;priority journal;prodromal Alzheimer disease;semantics;white matter,"Drago, V.;Babiloni, C.;Bartrés-Faz, D.;Caroli, A.;Bosch, B.;Hensch, T.;Didic, M.;Klafki, H. W.;Pievani, M.;Jovicich, J.;Venturi, L.;Spitzer, P.;Vecchio, F.;Schoenknecht, P.;Wiltfang, J.;Redolfi, A.;Forloni, G.;Blin, O.;Irving, E.;Davis, C.;Hrdemark, H. G.;Frisoni, G. B.",2011,,,0,
4578,White matter tract signatures of impaired social cognition in frontotemporal lobar degeneration,"Impairments of social cognition are often leading features in frontotemporal lobar degeneration (FTLD) and likely to reflect large-scale brain network disintegration. However, the neuroanatomical basis of impaired social cognition in FTLD and the role of white matter connections have not been defined. Here we assessed social cognition in a cohort of patients representing two core syndromes of FTLD, behavioural variant frontotemporal dementia (bvFTD; n = 29) and semantic variant primary progressive aphasia (svPPA; n = 15), relative to healthy older individuals (n = 37) using two components of the Awareness of Social Inference Test, canonical emotion identification and sarcasm identification. Diffusion tensor imaging (DTI) was used to derive white matter tract correlates of social cognition performance and compared with the distribution of grey matter atrophy on voxel-based morphometry. The bvFTD and svPPA groups showed comparably severe deficits for identification of canonical emotions and sarcasm, and these deficits were correlated with distributed and overlapping white matter tract alterations particularly affecting frontotemporal connections in the right cerebral hemisphere. The most robust DTI associations were identified in white matter tracts linking cognitive and evaluative processing with emotional responses: anterior thalamic radiation, fornix (emotion identification) and uncinate fasciculus (sarcasm identification). DTI associations of impaired social cognition were more consistent than corresponding grey matter associations. These findings delineate a brain network substrate for the social impairment that characterises FTLD syndromes. The findings further suggest that DTI can generate sensitive and functionally relevant indexes of white matter damage in FTLD, with potential to transcend conventional syndrome boundaries.",Aged;Atrophy/pathology;Diffusion Tensor Imaging/ methods;Female;Frontotemporal Dementia/ pathology/ physiopathology;Gray Matter/pathology;Humans;Male;Middle Aged;Primary Progressive Nonfluent Aphasia/ pathology/ physiopathology;Social Perception;White Matter/ pathology,"Downey, L. E.;Mahoney, C. J.;Buckley, A. H.;Golden, H. L.;Henley, S. M.;Schmitz, N.;Schott, J. M.;Simpson, I. J.;Ourselin, S.;Fox, N. C.;Crutch, S. J.;Warren, J. D.",2015,,10.1016/j.nicl.2015.06.005,0,
4579,MRI of carriers of the apolipoprotein E e4 allele-evidence for structural differences in normal-appearing brain tissue in e4+ relative to e4- young adults,"Apolipoprotein E is a protein involved in cholesterol and lipid transport. The gene coding for this protein has three different alleles: e2, e3 and e4. The e4 allele is recognised as a significant risk factor for the development of Alzheimer's disease in later life. Paradoxically, behavioural and functional evidence has demonstrated that the e4 allele may confer a cognitive advantage to the carrier in youth. In this article, a range of sophisticated and novel structural imaging techniques were used to identify subtle differences in the brain tissue of groups of young e4 and homozygous e3 carriers that might support this paradox. Using voxel-based morphometry of high-resolution structural MR images, we identified a higher white matter volume ratio in e4 relative to homozygous e3 carriers. Furthermore, diffusion tensor imaging and tract-based spatial statistics studies identified increases in axial diffusivity and mode of anisotropy in carriers of the e4 allele. In addition, quantitative magnetisation transfer data were analysed using tract-based spatial statistics. Evidence of a trend towards an increased transverse relaxation time of the bound proton pool was detected in e4 carriers, indicative of altered white matter composition. These changes were found to correlate with indices of cognitive performance across the two groups, supporting the notion that such subtle differences in white matter integrity may confer neural advantages that contribute to cognitive outcomes and, potentially, to performance differences, such as observed here in a test of verbal fluency and reported previously by other researchers. © 2013 John Wiley & Sons, Ltd.",,"Dowell, N. G.;Ruest, T.;Evans, S. L.;King, S. L.;Tabet, N.;Tofts, P. S.;Rusted, J. M.",2013,June,,0,
4580,Structural and resting-state MRI detects regional brain differences in young and mid-age healthy APOE-e4 carriers compared with non-APOE-e4 carriers,"The presence of the e4 allele of the apolipoprotein E (APOE) gene is the best-known genetic risk factor for Alzheimer's disease. In this study, we investigated the link between functional and behavioural differences and regional brain volume and cortical thickness differences in those who carry the e4 allele (e4+) and those who only carry the e3 allele (e3/e3). We studied these genotype populations in two age groups: a young group (average age, 21 years) and a mid-age group (average age, 50 years). High-resolution T1 -weighted MRI scans were analysed with Freesurfer to measure regional white matter brain volume and cortical thickness differences between genotype groups at each age. These data were correlated with behavioural findings in the same cohort. Resting-state MRI was also conducted to identify differences in underlying brain functional connectivity. We found that there was a positive correlation between the thickness of the parahippocampal cortex in young e4+ individuals and performance on an episodic memory task. Young e4+ individuals also showed a positive correlation between white matter volume in the left anterior cingulate and performance on a covert attention task. At mid-age, e4+ individuals had structural differences relative to e3/e3 individuals in these areas: the parahippocampal cortex was thicker and white matter volume in the left anterior cingulate was greater than in e3/e3 individuals. We discuss the possibility that an over-engagement with these regions by e4+ individuals in youth may have a neurogenic effect that is observable later in life. The cuneus appears to be an important region for APOE-driven differences in the brain, with greater functional connectivity among young e3/e3 individuals and greater white matter volume in young e4+ individuals. Copyright (c) 2016 John Wiley & Sons, Ltd.",apolipoprotein E e4;cortical thickness;neurogenesis;regional brain volume;resting-state MRI;white matter volume,"Dowell, N. G.;Evans, S. L.;Tofts, P. S.;King, S. L.;Tabet, N.;Rusted, J. M.",2016,May,10.1002/nbm.3502,0,
4581,The Cognition and Affect after Stroke - a Prospective Evaluation of Risks (CASPER) study: rationale and design,"BACKGROUND: Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain still rather unclear. The Cognition and Affect after Stroke: a Prospective Evaluation of Risks (CASPER) study has been primarily designed to examine whether stroke-specific (e.g. lesion location, volume, type, severity), cerebrovascular and neurodegenerative (e.g. white matter changes, atrophy, microbleeds, perivascular spaces), inflammatory, endothelial, and (epi)genetic markers are associated with cognitive impairment, post-stroke depression, and post-stroke apathy, and whether they predict their course over 12 months. The secondary aims are to investigate how the above-mentioned markers interact with each other, and to determine if patients with apathy and depression after stroke differ in pathogenesis, course, and outcome (e.g. functional outcome, neurocognitive performance, quality of life). METHODS/DESIGN: CASPER is a 1-year prospective clinical cohort follow-up study in 250 stroke patients recruited at the neurological in- and outpatient services at Maastricht University Medical Center (MUMC+, Maastricht, The Netherlands), and Zuyderland Medical Center (Sittard and Heerlen, The Netherlands). At baseline (3 months post-stroke), a neuropsychological assessment, neuropsychiatric interview, blood sample, and brain magnetic resonance imaging (MRI) scan are conducted. Assessment of neuropsychiatric and neurocognitive status are repeated 6 and 12 months later. DISCUSSION: The CASPER study investigates stroke-specific, vascular, neurodegenerative, inflammatory, and genetic markers of the development of vascular cognitive impairment, depression, and apathy after stroke. This creates the possibility to study not only the contribution of these individual markers but also their joint contribution, which differentiates this study from earlier stroke cohorts who lacked long-term follow-up data, a large sample size, an extensive MRI protocol, and markers from the blood. The knowledge we derive from this study might help in identifying markers that are associated with, or can predict the onset, maintenance, and progression of vascular cognitive impairment, depression, and apathy after stroke, and could provide new insights into possibilities for treatment and rehabilitation that result in better functional outcome after stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT02585349.",Apathy;Cognition;Dementia;Depression;Design;Neuroimaging;Stroke,"Douven, E.;Schievink, S. H.;Verhey, F. R.;van Oostenbrugge, R. J.;Aalten, P.;Staals, J.;Kohler, S.",2016,,10.1186/s12883-016-0588-1,0,
4582,Fulminant adult orthochromatic leucodystrophy,"A 27 year-old man from Marocco developed a progressive dementia leading within a year to a mutic akinetic state. The course of the disease was also marked by epileptic seizures. MRI revealed diffuse white matter involvement. A frontal white matter brain biopsy was consistent with the diagnosis of orthochromatic leucodystrophy, i.e: presence of sudanophilic lipids and pigmented cells associated with myelin loss. Adult forms of orthochromatic leucodystrophy are very rare. Our case was characterized by a fulminant course.",lipid;adult;article;brain biopsy;case report;human;human tissue;leukodystrophy;male;nuclear magnetic resonance imaging;seizure,"Dousset, V.;Tison, F.;Vital, A.;Henry, P.",1998,,,0,
4583,Brain microstructure reveals early abnormalities more than two years prior to clinical progression from mild cognitive impairment to Alzheimer's disease,"Diffusion imaging is a promising marker of microstructural damage in neurodegenerative disorders, but interpretation of its relationship with underlying neuropathology can be complex. Here, we examined both volumetric and brain microstructure abnormalities in 13 amnestic patients with mild cognitive impairment (MCI), who progressed to probable Alzheimer's disease (AD) no earlier than 2 years after baseline scanning, in order to focus on early, and hence more sensitive, imaging markers. We compared them to 22 stable amnestic MCI patients with similar cognitive performance and episodic memory impairment but who did not show progression of symptoms for at least 3 years. Significant group differences were mainly found in the volume and microstructure of the left hippocampus, while white matter group differences were also found in the body of the fornix, left fimbria, and superior longitudinal fasciculus (SLF). Diffusion index abnormalities in the SLF were the sign of a subtle microstructural injury not detected by standard atrophy measures in the corresponding gray matter regions. The microstructural measure obtained in the left hippocampus using diffusion imaging showed the most substantial differences between the two groups and was the best single predictor of future progression to AD. An optimal prediction model (91% accuracy, 85% sensitivity, 96% specificity) was obtained by combining MRI measures and CSF protein biomarkers. These results highlight the benefit of using the information of brain microstructural damage, in addition to traditional gray matter volume, to detect early, subtle abnormalities in MCI prior to clinical progression to probable AD and, in combination with CSF markers, to accurately predict such progression.","Aged;Alzheimer Disease/cerebrospinal fluid/ diagnosis/pathology;Amnesia/cerebrospinal fluid/ pathology;Amyloid beta-Peptides/cerebrospinal fluid;Atrophy/pathology;Brain/ pathology;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/cerebrospinal fluid/ pathology;Neuropsychological Tests;Peptide Fragments/cerebrospinal fluid;Phosphorylation;Predictive Value of Tests;Sensitivity and Specificity;tau Proteins/cerebrospinal fluid","Douaud, G.;Menke, R. A.;Gass, A.;Monsch, A. U.;Rao, A.;Whitcher, B.;Zamboni, G.;Matthews, P. M.;Sollberger, M.;Smith, S.",2013,Jan 30,10.1523/jneurosci.4437-12.2013,0,
4584,DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease,"Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects. As expected from the literature, all diffusion indices converged to show that the cingulum bundle, the uncinate fasciculus, the entire corpus callosum and the superior longitudinal fasciculus are the most affected white matter tracts in AD. Significant differences between MCI and AD were essentially confined to the corpus callosum. More importantly, we introduce for the first time in a degenerative disorder an application of a recently developed tensor index, the ""mode"" of anisotropy, as well as probabilistic crossing-fibre tractography. The mode of anisotropy specifies the type of anisotropy as a continuous measure reflecting differences in shape of the diffusion tensor ranging from planar (e.g., in regions of crossing fibres from two fibre populations of similar density or regions of ""kissing"" fibres) to linear (e.g., in regions where one fibre population orientation predominates), while probabilistic crossing-fibre tractography allows to accurately trace pathways from a crossing-fibre region. Remarkably, when looking for whole-brain diffusion differences between MCI patients and healthy subjects, the only region with significant abnormalities was a region of crossing fibres in the centrum semiovale, showing an increased mode of anisotropy. The only white matter region demonstrating a significant difference in correlations between neuropsychological scores and a diffusion measure (mode of anisotropy) across the three groups was the same region of crossing fibres. Further examination using probabilistic tractography established explicitly and quantitatively that this previously unreported increase of mode and co-localised increase of fractional anisotropy was explained by a relative preservation of motor-related projection fibres (at this early stage of the disease) crossing the association fibres of the superior longitudinal fasciculus. These findings emphasise the benefit of looking at the more complex regions in which spared and affected pathways are crossing to detect very early alterations of the white matter that could not be detected in regions consisting of one fibre population only. Finally, the methods used in this study may have general applicability for other degenerative disorders and, beyond the clinical sphere, they could contribute to a better quantification and understanding of subtle effects generated by normal processes such as visuospatial attention or motor learning. © 2010 Elsevier Inc.",Alzheimer disease;anisotropy;article;brain blood flow;brain region;controlled study;corpus callosum;diffusion tensor imaging;human;major clinical study;mild cognitive impairment;nerve fiber;nerve projection;neuropsychological test;priority journal;probability;tractography;uncinate fasciculus;white matter;Allegra,"Douaud, G.;Jbabdi, S.;Behrens, T. E. J.;Menke, R. A.;Gass, A.;Monsch, A. U.;Rao, A.;Whitcher, B.;Kindlmann, G.;Matthews, P. M.;Smith, S.",2011,,,0,
4585,In vivo evidence for the selective subcortical degeneration in Huntington's disease,"Although Huntington's disease is largely considered to be a subcortical disease, there is no clear consensus on whether all deep grey matter loss is a direct downstream consequence of the massive degeneration of the medium-size spiny neurons in the striatum. Our aim was to characterise in vivo such preferential degeneration by analysing various distinct diffusion imaging measures including mean diffusivity, anisotropy, fibre orientation (using the information of the principal diffusion direction) and white matter tractography. All results converged to demonstrate the selective degeneration of connections in subcortical grey and white matter, degeneration which was likely to originate with the death of the striatal medium-size spiny neurons. Indeed, we found a significant increase of MD and FA in all the subcortical grey matter structures involved in the cortico-striato-thalamo-cortical loops. The atypical striatal and pallidal increase of FA was concurrent to a decrease of the dispersion of the fibre orientation, unambiguously characterising a preferential loss of connections along specific radiating directions from these structures while some others are comparatively spared. Analysis of striatal and pallidal white matter tracts revealed that striato-pallidal projections were the most affected. The ability of DTI to uncover the impact of such neurodegenerative disease on some specific neuronal/axonal populations is a further step towards the future definition of a surrogate marker of this disease. Beyond Huntington's disease, we prove here that diffusion imaging technique, associated to adequate methodological analyses, can provide insight into any neurodegenerative disorder for which some neuronal populations or connections are selectively targeted over others.","Adult;Brain/ pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Huntington Disease/ pathology;Image Interpretation, Computer-Assisted;Male;Middle Aged;Nerve Degeneration/ pathology","Douaud, G.;Behrens, T. E.;Poupon, C.;Cointepas, Y.;Jbabdi, S.;Gaura, V.;Golestani, N.;Krystkowiak, P.;Verny, C.;Damier, P.;Bachoud-Levi, A. C.;Hantraye, P.;Remy, P.",2009,Jul 15,10.1016/j.neuroimage.2009.03.044,0,
4586,Automatic Detection of Cerebral Microbleeds from MR Images via 3D Convolutional Neural Networks,"Cerebral microbleeds (CMBs) are small haemorrhages nearby blood vessels. They have been recognized as important diagnostic biomarkers for many cerebrovascular diseases and cognitive dysfunctions. In current clinical routine, CMBs are manually labelled by radiologists but this procedure is laborious, time-consuming, and error prone. In this paper, we propose a novel automatic method to detect CMBs from magnetic resonance (MR) images by exploiting the 3D convolutional neural network (CNN). Compared with previous methods that employed either low-level hand-crafted descriptors or 2D CNNs, our method can take full advantage of spatial contextual information in MR volumes to extract more representative high-level features for CMBs, and hence achieve a much better detection accuracy. To further improve the detection performance while reducing the computational cost, we propose a cascaded framework under 3D CNNs for the task of CMB detection. We first exploit a 3D fully convolutional network (FCN) strategy to retrieve the candidates with high probabilities of being CMBs, and then apply a well-trained 3D CNN discrimination model to distinguish CMBs from hard mimics. Compared with traditional sliding window strategy, the proposed 3D FCN strategy can remove massive redundant computations and dramatically speed up the detection process. We constructed a large dataset with 320 volumetric MR scans and performed extensive experiments to validate the proposed method, which achieved a high sensitivity of 93.16% with an average number of 2.74 false positives per subject, outperforming previous methods using low-level descriptors or 2D CNNs by a significant margin. The proposed method, in principle, can be adapted to other biomarker detection tasks from volumetric medical data.",aged;article;artificial neural network;automation;brain hemorrhage;brain mapping;cerebrovascular accident;comparative study;controlled study;diagnostic accuracy;false negative result;human;image analysis;image processing;major clinical study;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;sensitivity and specificity;three dimensional convolutional neural network;three dimensional imaging,"Dou, Q.;Chen, H.;Yu, L.;Zhao, L.;Qin, J.;Wang, D.;Mok, V. C. T.;Shi, L.;Heng, P. A.",2016,,,0,
4587,A novel NOTCH3 frameshift deletion and mitochondrial abnormalities in a patient with CADASIL,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which leads to strokes and dementia, is caused by single missense mutations or, in a few cases, small deletions in the NOTCH3 gene. These mutations result in a gain or a loss of 1 (or, rarely, 3) cysteine residue in 1 of 34 epidermal growth factor-like repeats in the extracellular amino-terminal region of NOTCH3. Objective: To describe a patient with a novel NOTCH3 mutation in whom clinical and laboratory findings of mitochondrial abnormalities were associated with a diagnosis of CADASIL. Patients: A patient with a history of migraines, repeated transient ischemic attacks, and generalized fatigue underwent muscle biopsy, brain magnetic resonance spectroscopic imaging, and screening of mitochondrial DNA and NOTCH3. Results: Molecular genetic analysis showed a NOTCH3 mutation (the first documented frameshift deletion in a patient with CADASIL) in exon 4. Although the screening of mitochondrial DNA did not show mitochondrial mutations, findings from muscle biopsy and brain magnetic resonance spectroscopic imaging showed signs of mitochondrial impairment (ultrastructural mitochondrial abnormalities and increased parenchymal brain lactate, respectively). Conclusions: A patient with CADASIL and a 5-base pair deletion leading to a frameshift mutation showed clinical and laboratory evidence of mitochondrial dysfunction. This adds to the previously reported hypothesis of a pathogenetic role of NOTCH3 or, less specifically, a microvascular pathologic effect on mitochondrial energy metabolism.",,"Dotti, M. T.;De Stefano, N.;Bianchi, S.;Malandrini, A.;Battisti, C.;Cardaioli, E.;Federico, A.",2004,June,,0,
4588,Temporal relationships between depressive symptoms and white matter hyperintensities in older men and women,"OBJECTIVE: Associations between vascular disease and depression in late life, including increased white matter hyperintensities (WMHs), have been reported. Whether depression is an etiology or a consequence of vascular disease is still unknown. We investigated the temporal relationship between depressive symptoms and WMHs in older men and women. METHODS: We utilized data from 90 dementia-free older adults (39 women, 51 men), 57 years of age and older at baseline, from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. Participants were followed for up to 8 years. Ratings of white matter disease burden were available for the first, last, and at least one interim visit, and participants completed the Center for Epidemiologic Studies Depression Scale (CES-D) annually. Statistical models, performed separately in men and women, examined whether depressive symptoms predicted subsequent WMH ratings or WMHs predicted subsequent depressive symptoms. RESULTS: The total CES-D score was not associated with WMHs in men or women. In men, the CES-D depressed mood subscale predicted accelerating longitudinal increases in WMHs at older ages, but WMHs did not predict subsequent depressive symptoms. In women, there were no significant associations between the CES-D depressed mood subscale and WMHs. CONCLUSIONS: White matter disease may be a consequence of depressed mood in men but not in women. Intervention strategies for depression may slow the progression of white matter disease in older men. These results add to previous findings documenting sex differences in the correlates of depressive disorders in late life.","Aged;Aged, 80 and over;Depressive Disorder/*complications/diagnosis/pathology;Female;Humans;Leukoencephalopathies/*complications/psychology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Psychiatric Status Rating Scales;Regression Analysis;Sex Factors","Dotson, V. M.;Zonderman, A. B.;Kraut, M. A.;Resnick, S. M.",2013,Jan,10.1002/gps.3791,0,
4589,Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study,"BACKGROUND: Late-life depression is associated with decreased brain volumes, particularly in frontal and temporal areas. Evidence suggests that depressive symptoms at a subclinical level are also associated with brain atrophy in these regions, but most of these associations are based on cross-sectional data. Our objective was to investigate both cross-sectional and longitudinal relations between sub-threshold depressive symptoms and brain volumes in older adults and to examine whether these associations are modified by age. METHODS: In total, 110 dementia-free adults from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging aged 56 years and older at baseline participated in this study. Participants received annual evaluations for up to 9 years, during which structural magnetic resonance imaging (MRI) scans were acquired and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. RESULTS: Mean depressive symptom scores over time were associated with grey matter volume reductions in the left temporal lobe. Depressive symptoms were associated with brain volume reductions with advancing age in the cingulate gyrus and orbitofrontal cortex. Moreover, individuals with higher mean depressive symptom scores showed a faster rate of volume decline in left frontal white matter. Depressive symptoms were not associated with hippocampus volumes. LIMITATIONS: Limitations include the relative homogeneity of our primarily white and highly educated sample, the lack of information about age at onset of depressive symptoms and potential limitations of the automated brain volume registration. CONCLUSION: Our results suggest that depressive symptoms, even at a subthreshold level, are associated with volume reductions in specific frontal and temporal brain regions, particularly with advancing age.","Aged;Aged, 80 and over;Antidepressive Agents/therapeutic use;Brain/ pathology;Depression/drug therapy/ pathology;Female;Frontal Lobe/pathology;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size;Psychological Tests;Regression Analysis;Sex Characteristics;Temporal Lobe/pathology","Dotson, V. M.;Davatzikos, C.;Kraut, M. A.;Resnick, S. M.",2009,Sep,,0,
4590,Statin use and hippocampal volumes in elderly subjects at risk for Alzheimer's disease: A pilot observational study,"Statins are investigational therapies for preventing or treating Alzheimer's disease (AD) and mild cognitive impairment (MCI). Hippocampal atrophy is a characteristic feature of MCI and AD. This study analyzed cross-sectional data from 246 non-demented elderly subjects to test the effect of lipid lowering agent (LLA) therapy on cognition and brain magnetic resonance imaging (MRI) measures of white matter lesions and hippocampal volume. The study also compared rates of hippocampal volume change over two and four years in a smaller subset. At baseline, LLA users were younger, better educated, more likely to be male, and had higher cognitive scores. Cognitive performance also varied by age and gender, and MRI measures varied by age. After adjusting for these differences, the effect of LLA use on baseline cognition, baseline hippocampal volume, and baseline white matter lesion scores was not significant. The effect of LLA use on hippocampal volume loss at two-year and four-year follow-ups was also not significant. This study is the first to examine statin effects on brain atrophy measured by MRI. In this cohort, statin use was not associated with rate of change of hippocampal volume. While the study was limited by a relatively small number of statin users, the findings seem consistent with three prior randomized trials that found no cognitive benefits for statins in nondemented subjects. Prospective studies in both nondemented and AD subjects may provide more conclusive answers.",,"Doraiswamy, P. M.;Steffens, D. C.;McQuoid, D. R.",2004,September/October,,0,
4591,Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia,"OBJECTIVE: We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations. METHODS: In this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex. RESULTS: Although carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happe cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found. CONCLUSIONS: This study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.",Adult;Aged;Brain Chemistry/genetics;Case-Control Studies;Female;Frontal Lobe/metabolism/pathology;Frontotemporal Dementia/genetics/ pathology/ physiopathology;Genetic Predisposition to Disease;Humans;Male;Middle Aged;Mutation/genetics;Nerve Net/ pathology/ physiopathology;Risk;Structure-Activity Relationship,"Dopper, E. G.;Rombouts, S. A.;Jiskoot, L. C.;Heijer, T.;de Graaf, J. R.;Koning, I.;Hammerschlag, A. R.;Seelaar, H.;Seeley, W. W.;Veer, I. M.;van Buchem, M. A.;Rizzu, P.;van Swieten, J. C.",2013,Feb 26,10.1212/WNL.0b013e31828407bc,0,
4592,Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer's disease: Comparison to small vessel ischemic vascular dementia,"Objective: The objective of this study was to compare psychometric profiles of Alzheimer's disease (AD) patients with subcortical magnetic resonance imaging (MRI) signal abnormalities to those of AD patients without such MRI findings (normal subcortical MRI) and to those of patients with ischemic vascular dementia (IVD) associated with small and primarily subcortical ischemic changes. Background: The cognitive significance of MRI white matter and other subcortical abnormalities in AD is unknown. Prior studies comparing AD patients with white matter changes on MRI have not included IVD patients with comparable MRI findings. If white matter/subcortical changes in AD reflect vascular abnormalities, they might be associated with cognitive profiles similar to those seen in subcortical IVD. Method: We studied 15 AD patients with normal subcortical MRIs, 22 AD patients with subcortical MRI hyperintensities, and 18 IVD (NINCDS-ADRDA and NINDS-AIREN criteria) at the Alzheimer's Disease Research Center of the Baylor College of Medicine. IVD patients had predominantly small and subcortical signal abnormalities, and none had large cortical infarcts. AD patients had only nonspecific subcortical signal abnormalities with or without atrophy (atrophy was not analyzed). We compared the AD group with abnormal MRIs to the AD group with normal subcortical MRIs and the AD group to the IVD group using ANCOVA planned comparisons (dementia severity and education covaried). Results: AD patients with abnormal MRIs did not differ significantly from AD patients with normal subcortical MRIs on any of the neuropsychological measures. AD patients exhibited significantly better attention/concentration, visuospatial/visuoconstructional performance, letter fluency, motor programming, and simple motor speed than IVD patients as well as significantly worse delayed verbal recognition memory. Because MRI changes were generally more extensive in IVD, a subset of AD patients with abnormal subcortical MRIs was compared to a subset of IVD patients matched for degree of MRI signal abnormalities. These subsets of AD and IVD patients still showed distinctive neuropsychological profiles. Conclusions:",,"Doody, R. S.;Massman, P. J.;Mawad, M.;Nance, M.",1998,October,,0,
4593,Does APO ε4 correlate with MRI changes in Alzheimer's disease?,"Objective - To assess the relation between APO E genotype and MRI white matter changes in Alzheimer's disease. The APO ε4 allele is correlated with amyloid angiopathy and other neuropathologies in Alzheimer's disease and could be associated with white matter changes. If so, there should be a dose effect. Methods - 104 patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) in this Alzheimer's Disease Research Centre were studied. Patients received MRI and APO E genotyping by standardised protocols. Axial MRI was scored (modified Schelten's scale) for the presence and degree of white matter changes and atrophy in several regions by a neuroradiologist blinded to genotype. Total white matter and total atrophy scores were also generated. Data analysis included Pearson's correlation for regional and total imaging scores and analysis of variance (ANOVA) (or Kruskal-Wallis) and X(2) for demographic and disease related variables. Results - 30 patients had no ε4, 53 patients were heterozygous, and 21 patients were homozygous. The three groups did not differ in sex distribution, age of onset, age at MRI, MMSE, clinical dementia rating, or modified Hachinski ischaemia scores. There were no significant correlations between total or regional white matter scores and APO E genotype (Pearson correlation). Conclusions - No correlation between total or regional white matter scores and APO E genotype was found. The pathogenesis of white matter changes in Alzheimer's disease may be independent of APO E genotype.",,"Doody, R. S.;Azher, S. N.;Haykal, H. A.;Dunn, J. K.;Liao, T.;Schneider, L.",2000,November,,0,
4594,Acute psychosis revailing sub-cortical lesion in AIDS,"Maccario et al. described, in 1987 the case of an HIV-positive patient whose psychotic symptomatology was the expression of right centrum semi-ovale lesion. We report the case of a patient who suffered a sudden delirium, expression of a probable right lenticular cerebral toxoplasmosis. This 35-year-old male homosexual, who had no psychiatric history, suddenly developed in November 1988 the following psychiatric signs: he started to walk back and forth incessantly, he had the impression that he was the subject of the conversations of the passers-by, that all the posters and notices refer to him, and that he was God. He was admitted in a psychiatric department where the symptoms were progressively curbed by neuroleptics (cyamemazine 75 mg, and haloperidol 15 mg). The episode was not questionned by the patient, but attributed to bad eating habits. HIV-positivity had been discovered a year later (during systematic screening). A computerized tomographic (CT) scan performed subsequently to this delirium was interpreted as normal. Four weeks later the patient was referred to us. The psychiatric condition was stabilized in spite of a certain agressiveness and the probable persistance of an underlying delirium state. Laboratory examinations showed the following: blood count revealed leukopenia (2.2 G/l) and thrombocytopenia (135 G/l); OKT4/OKT8 ratio was 0.08; CSF: normal; sputum culture evidenced the presence of pneumocystis carinii; EEG were normal. Neuropsychological symptoms concerned in particular a lack of concentration during the different tests with a definitive wavering of attention. Lexical retrieval was poor whatever the topic proposed. Depressive topics were frequent. The CT scan evidenced a hyperdensity with an oedemous halo, in the region of the basal ganglia, sustaining the diagnosis of cerebral neurotoxoplasmosis. It was definitely lenticular in shape, with confirmation by NMR. Systemic treatment of toxoplasmosis by concomittant pyrimethamine 100 mg, and sulfadiazine (500 mg x 8) was begun, but unfortunately the patient has been lost from sight. The unveiling of neuro-AIDS by psychiatric symptomatology is a well known fact since the description of HIV encephalopathy by Navia et al. The interest of this case consists in the detection of a focal lesion during an isolated psychiatric episode. To our knowledge, there is no other observation (Maccario's case included) associating focal lesion and psychiatric disorders. The exact nature of the lesion remained often unknown because these subjects are undisciplined. It is difficult to categorically attribute the psychotic episode to the right lenticular lesion. In such symptoms, an HIV encephalopathy can be debated. The notion of an unilateral lesion is not in favour of this hypothesis. Indeed in HIV encephalitis, magnetic resonance scan reveal often diffuse bilateral patchy and confluent areas in white matter. Troubles attributed to basal ganglia remained exclusively motor for a long time. However, the relationship between basal ganglia and psychiatric symptoms has been often debated, but remained always problematical on account of the insignificant number of cases. A clear example of this association is depicted in the idiopathic calcification syndrome of basal ganglia. Psychotic signs are often unveiling and thus precede the onset of a demential syndrome. Such phenomena have also been described in sub-cortical disorders such as Wilson's or Huntington's disease. However, the bliateral nature of sub cortical lesions in such diseases is well established. Neurobehavioral changes associated with unilateral caudate lesions have been described. In conclusion, we want to emphasize the importance of CT scan during isolated psychiatric disorders in HIV positive patients.",cyamemazine;haloperidol;pyrimethamine;sulfadiazine;acquired immune deficiency syndrome;adult;article;brain injury;case report;computer assisted tomography;human;male;priority journal;psychosis,"Donnet, A.;Harle, J. R.;Cherif, A. A.;Gastaut, J. A.;Weiller, P. J.",1991,,,0,
4595,Yield of screening for CADASIL mutations in lacunar stroke and leukoaraiosis,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic disorder typified by early onset lacunar strokes, subcortical dementia, psychiatric disturbances, and migraine. Mutations in the Notch3 gene are responsible. Atypical phenotypes have been recognized, and the disease is probably underdiagnosed in the wider stroke population. Therefore, we determined the yield of screening for Notch3 mutations in lacunar stroke with or without leukoaraiosis. METHODS: Two hundred eighteen consecutive patients were studied. All had brain and carotid imaging. Polymerase chain reaction-single-stranded conformational polymorphism analysis was used to screen exons 3, 4, 5, and 6 of the Notch3 gene for mutations and polymorphisms. RESULTS: A single mutation in exon 4 (C697T) was identified in a young patient, giving an overall carrier frequency of 0.05% (95% CI, 0.0 to 2.0). For patients with onset of lacunar stroke at < or =65 years and leukoaraiosis, the yield was 2.0% (95% CI, 0.4 to 10.9). CONCLUSIONS: Notch3 mutations are rare in patients with typical strokes due to cerebral small-vessel disease. In the absence of classic features suggestive of CADASIL, screening for Notch3 mutations has a low yield.","Adult;Aged;Cerebral Cortex/abnormalities;Dementia, Multi-Infarct/complications/ diagnosis/genetics;Female;Genetic Testing;Humans;Male;Middle Aged;Mutation;Polymorphism, Genetic;Proto-Oncogene Proteins/ genetics;Receptors, Cell Surface;Receptors, Notch;Stroke/ complications","Dong, Y.;Hassan, A.;Zhang, Z.;Huber, D.;Dalageorgou, C.;Markus, H. S.",2003,Jan,,0,
4596,MRI linear measures of brain regional atrophy in mild Alzheimer disease,"Objective: To assess the sensitivity and specificity of linear measures of brain atrophy in the diagnosis of Alzheimer disease (AD) in the early stages. Methods: Linear measures of regional frontal lobe (bifrontal index, interhemispheric fissure width), medial temporal lobe (interuncal distance, minimal thickness of the medial temporal lobe), and hippocampus (hippocampal height, width of the choroid fissure, width of the temporal horn and distance between the hippocampus and brain stem), indicating the indeces of brain atrophy were made on the magnified MRI obtained in 30 patients with mild AD, 20 patients with multi-infarct dementia (MID) and 20 control subjects. Results: The measure with the best sensitivity in discriminating AD patients from MID and control subjects was the width of the temporal horn, the sensitivity being 90% and the specificity being 85%. A compound measure of the width of the temporal horn, the width of the choroid fissure; the interuncal distance, the hippocampal height and the distance between the hippocampus and brain stem could discriminate the patients with mild AD from MID and the control subjects with 93% sensitivity and 95% specificity. Conclusion: Linear measures of hippocampal atrophy can be of use in the routine diagnosis of AD, even in its early stages.",Alzheimer disease;article;brain atrophy;clinical article;controlled study;diagnostic accuracy;diagnostic imaging;early diagnosis;frontal lobe;hippocampus;human;multiinfarct dementia;nuclear magnetic resonance imaging;temporal lobe,"Dong, H.;Yan, Z.;Li, K.",1998,,,0,
4597,"Heterogeneity of neuroanatomical patterns in prodromal Alzheimer's disease: links to cognition, progression and biomarkers","See Coulthard and Knight (doi:10.1093/aww335) for a scientific commentary on this article.Individuals with mild cognitive impairment and Alzheimer's disease clinical diagnoses can display significant phenotypic heterogeneity. This variability likely reflects underlying genetic, environmental and neuropathological differences. Characterizing this heterogeneity is important for precision diagnostics, personalized predictions, and recruitment of relatively homogeneous sets of patients into clinical trials. In this study, we apply state-of-the-art semi-supervised machine learning methods to the Alzheimer's disease Neuroimaging cohort (ADNI) to elucidate the heterogeneity of neuroanatomical differences between subjects with mild cognitive impairment (n = 530) and Alzheimer's disease (n = 314) and cognitively normal individuals (n = 399), thereby adding to an increasing literature aiming to establish neuroanatomical and neuropathological (e.g. amyloid and tau deposition) dimensions in Alzheimer's disease and its prodromal stages. These dimensional approaches aim to provide surrogate measures of heterogeneous underlying pathologic processes leading to cognitive impairment. We relate these neuroimaging patterns to cerebrospinal fluid biomarkers, white matter hyperintensities, cognitive and clinical measures, and longitudinal trajectories. We identified four such atrophy patterns: (i) individuals with largely normal neuroanatomical profiles, who also turned out to have the least abnormal cognitive and cerebrospinal fluid biomarker profiles and the slowest clinical progression during follow-up; (ii) individuals with classical Alzheimer's disease neuroanatomical, cognitive, cerebrospinal fluid biomarkers and clinical profile, who presented the fastest clinical progression; (iii) individuals with a diffuse pattern of atrophy with relatively less pronounced involvement of the medial temporal lobe, abnormal cerebrospinal fluid amyloid-beta1-42 values, and proportionally greater executive impairment; and (iv) individuals with notably focal involvement of the medial temporal lobe and a slow steady progression, likely representing in early Alzheimer's disease stages. These four atrophy patterns effectively define a 4-dimensional categorization of neuroanatomical alterations in mild cognitive impairment and Alzheimer's disease that can complement existing dimensional approaches for staging Alzheimer's disease using a variety of biomarkers, which offer the potential for enabling precision diagnostics and prognostics, as well as targeted patient recruitment of relatively homogeneous subgroups of subjects for clinical trials.","0 (Amyloid beta-Peptides);0 (Apolipoproteins E);0 (Biomarkers);0 (Peptide Fragments);0 (amyloid beta-protein (1-42));0 (tau Proteins);Alzheimer Disease/cerebrospinal fluid/complications/diagnostic imaging/pathology;Amyloid beta-Peptides/cerebrospinal fluid;Analysis of Variance;Apolipoproteins E/genetics;Biomarkers/ cerebrospinal fluid;Cluster Analysis;Cognition Disorders/cerebrospinal fluid/diagnostic imaging/etiology/pathology;Cohort Studies;Cross-Sectional Studies;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Peptide Fragments/cerebrospinal fluid;Prodromal Symptoms;White Matter/diagnostic imaging/pathology;tau Proteins/cerebrospinal fluid;dementia;mild cognitive impairment;neuroanatomical heterogeneity;pattern analysis","Dong, A.;Toledo, J. B.;Honnorat, N.;Doshi, J.;Varol, E.;Sotiras, A.;Wolk, D.;Trojanowski, J. Q.;Davatzikos, C.;Alzheimer's Disease Neuroimaging, Initiative",2017,Mar 1,,0,4598
4598,"Heterogeneity of neuroanatomical patterns in prodromal Alzheimer's disease: links to cognition, progression and biomarkers","Individuals with mild cognitive impairment and Alzheimer's disease clinical diagnoses can display significant phenotypic heterogeneity. This variability likely reflects underlying genetic, environmental and neuropathological differences. Characterizing this heterogeneity is important for precision diagnostics, personalized predictions, and recruitment of relatively homogeneous sets of patients into clinical trials. In this study, we apply state-of-the-art semi-supervised machine learning methods to the Alzheimer's disease Neuroimaging cohort (ADNI) to elucidate the heterogeneity of neuroanatomical differences between subjects with mild cognitive impairment (n = 530) and Alzheimer's disease (n = 314) and cognitively normal individuals (n = 399), thereby adding to an increasing literature aiming to establish neuroanatomical and neuropathological (e.g. amyloid and tau deposition) dimensions in Alzheimer's disease and its prodromal stages. These dimensional approaches aim to provide surrogate measures of heterogeneous underlying pathologic processes leading to cognitive impairment. We relate these neuroimaging patterns to cerebrospinal fluid biomarkers, white matter hyperintensities, cognitive and clinical measures, and longitudinal trajectories. We identified four such atrophy patterns: (i) individuals with largely normal neuroanatomical profiles, who also turned out to have the least abnormal cognitive and cerebrospinal fluid biomarker profiles and the slowest clinical progression during follow-up; (ii) individuals with classical Alzheimer's disease neuroanatomical, cognitive, cerebrospinal fluid biomarkers and clinical profile, who presented the fastest clinical progression; (iii) individuals with a diffuse pattern of atrophy with relatively less pronounced involvement of the medial temporal lobe, abnormal cerebrospinal fluid amyloid-beta1-42 values, and proportionally greater executive impairment; and (iv) individuals with notably focal involvement of the medial temporal lobe and a slow steady progression, likely representing in early Alzheimer's disease stages. These four atrophy patterns effectively define a 4-dimensional categorization of neuroanatomical alterations in mild cognitive impairment and Alzheimer's disease that can complement existing dimensional approaches for staging Alzheimer's disease using a variety of biomarkers, which offer the potential for enabling precision diagnostics and prognostics, as well as targeted patient recruitment of relatively homogeneous subgroups of subjects for clinical trials.",dementia;magnetic resonance imaging;mild cognitive impairment;neuroanatomical heterogeneity;pattern analysis,"Dong, A.;Toledo, J. B.;Honnorat, N.;Doshi, J.;Varol, E.;Sotiras, A.;Wolk, D.;Trojanowski, J. Q.;Davatzikos, C.;Alzheimer's Disease Neuroimaging, Initiative",2016,Dec 20,,0,
4599,HIV Encephalopathy: Pediatric case series description and insights from the clinic coalface,"Background: The Human Immune Deficiency Virus (HIV) can manifest neurologically in both adults and children. Early invasion of the central nervous system by the virus, affecting the developing brain, is believed to result in the most common primary HIV-related neurological complication, HIV Encephalopathy (HIVE). In countries such as South Africa where many children have not been initiated on antiretroviral treatment early, HIVE remains a significant clinical problem. Methods: Children were selected from a clinic for children with neurologic complications of HIV, located at the Red Cross War Memorial Children's Hospital, South Africa 2008-2012. Eligible subjects fulfilled the following inclusion criteria: aged 6 months-13 years; positive diagnosis of HIV infection, vertically infected and HIVE as defined by CDC criteria. Each participant was prospectively assessed by a Pediatric Neurologist using a standardized proforma which collated relevant details of background, clinical and immunological status. Results: The median age of the 87 children was 64 months (interquartile range 27-95 months). All except one child were on antiretroviral treatment, 45% had commenced treatment <12 months of age. Delayed early motor milestones were reported in 80% and delayed early speech in 75% of children in whom we had the information. Twenty percent had a history of one or more seizures and 41% had a history of behavior problems. Forty-eight percent had microcephaly and 63% a spastic diplegia. CD4 percentages followed a normal distribution with mean of 30.3% (SD 8.69). Viral loads were undetectable (<log 1.6) in 70% of the children. Brain imaging was performed on 56% with 71% of those imaged demonstrating at least one abnormality, most commonly white matter volume loss or signal abnormality. Conclusions: Amongst the cohort of children referred to this clinic, the diagnosis of HIVE was unrecognized in the general medical services, even in its most severe form. Developmental delay and school failure were major presenting problems. Co-morbidities are a frequent finding and should be sought actively in order to optimize management and promote best possible outcomes for this vulnerable group of children.",,"Donald, K. A.;Walker, K. G.;Kilborn, T.;Carrara, H.;Langerak, N. G.;Eley, B.;Wilmshurst, J. M.",2015,,,0,
4600,Vessel-encoded arterial spin labeling (VE-ASL) reveals elevated flow territory asymmetry in older adults with substandard verbal memory performance,"PURPOSE: To evaluate how flow territory asymmetry and/or the distribution of blood through collateral pathways may adversely affect the brain's ability to respond to age-related changes in brain function. These patterns have been investigated in cerebrovascular disease; however, here we evaluated how flow-territory asymmetry related to memory generally in older adults. MATERIALS AND METHODS: A multi-faceted MRI protocol, including vessel-encoded arterial spin labeling capable of flow territory mapping, was applied to assess how flow territory asymmetry; memory performance (CERAD-Immediate Recall); cortical cerebral blood flow (CBF), white matter lesion (WML) count, and cortical gray matter volume were related in older healthy control volunteers (HC; n = 15; age = 64.5 +/- 7 years) and age-matched mild cognitive impairment volunteers (MCI; n = 7; age = 62.7 +/- 3.7 years). RESULTS: An inverse relationship was found between memory performance and flow territory asymmetry in HC volunteers (P = 0.04), which reversed in MCI volunteers (P = 0.04). No relationship was found between memory performance and cortical tissue volume in either group (P > 0.05). Group-level differences for HC volunteers performing above versus below average on CERAD-I were observed for flow territory asymmetry (P < 0.02) and cortical volume (P < 0.05) only. CONCLUSION: Findings suggest that flow territory asymmetry may correlate more sensitively with memory performance than CBF, atrophy and WML count in older adults.","Adult;Aging/pathology;Blood Flow Velocity;Brain/*pathology/*physiopathology;Cerebral Angiography/methods;*Cerebrovascular Circulation;Female;Humans;Magnetic Resonance Angiography/methods;Male;Memory;Memory Disorders/*physiopathology;Middle Aged;Nerve Fibers, Myelinated/*pathology;Reproducibility of Results;Sensitivity and Specificity;Spin Labels;*Verbal Behavior;ageing;cerebral blood flow;dementia;flow territory asymmetry;vessel encoded arterial spin labeling (VE-ASL)","Donahue, M. J.;Hussey, E.;Rane, S.;Wilson, T.;van Osch, M.;Hartkamp, N.;Hendrikse, J.;Ally, B. A.",2014,Feb,10.1002/jmri.24150,0,
4601,Multi-modal neuroimaging in premanifest and early Huntington's disease: 18 month longitudinal data from the IMAGE-HD study,"IMAGE-HD is an Australian based multi-modal longitudinal magnetic resonance imaging (MRI) study in premanifest and early symptomatic Huntington's disease (pre-HD and symp-HD, respectively). In this investigation we sought to determine the sensitivity of imaging methods to detect macrostructural (volume) and microstructural (diffusivity) longitudinal change in HD. We used a 3T MRI scanner to acquire T1 and diffusion weighted images at baseline and 18 months in 31 pre-HD, 31 symp-HD and 29 controls. Volume was measured across the whole brain, and volume and diffusion measures were ascertained for caudate and putamen. We observed a range of significant volumetric and, for the first time, diffusion changes over 18 months in both pre-HD and symp-HD, relative to controls, detectable at the brain-wide level (volume change in grey and white matter) and in caudate and putamen (volume and diffusivity change). Importantly, longitudinal volume change in the caudate was the only measure that discriminated between groups across all stages of disease: far from diagnosis (>15 years), close to diagnosis (<15 years) and after diagnosis. Of the two diffusion metrics (mean diffusivity, MD; fractional anisotropy, FA), only longitudinal FA change was sensitive to group differences, but only after diagnosis. These findings further confirm caudate atrophy as one of the most sensitive and early biomarkers of neurodegeneration in HD. They also highlight that different tissue properties have varying schedules in their ability to discriminate between groups along disease progression and may therefore inform biomarker selection for future therapeutic interventions.",Adult;Female;Humans;Huntington Disease/ diagnosis;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neuroimaging/ methods,"Dominguez, D. J.;Egan, G. F.;Gray, M. A.;Poudel, G. R.;Churchyard, A.;Chua, P.;Stout, J. C.;Georgiou-Karistianis, N.",2013,,10.1371/journal.pone.0074131,0,
4602,Progressive multifocal cerebral infarction associated with intravascular large B-cell lymphoma: A case report,"Intravascular large B-cell lymphoma is a rare variant of large B-cell lymphoma, according to the current WHO classification. It has a non-specific clinical presentation and is characterised by absence of marked lymphoadenopathy and aggressive behaviour. Its diagnosis is extremely difficult and many of the reported cases were diagnosed post-mortem. We report the case of an 82-year-old woman who presented with the clinical features of progressive multifocal cerebral infarction. Her neurological condition subsequently deteriorated. A brain MRI showed multistage intraparenchymal infarction and haemorrhage in the cerebral hemispheres. The hallmark in this lymphoma is the triad of a subacute encephalopathy, multiple strokes and elevated serum lactate dehydrogenase (LDH) levels. Clinical differential diagnoses should include cerebral vasculitis, septic encephalopathy or infections of the central nervous system. Differential pathological diagnoses include other angiotropic tumours such as T/NK lymphomas, lymphomatoid granulomatosis, undifferentiated carcinoma or malignant melanoma. © 2012 SEAP y SEC.",lactate dehydrogenase;aged;article;autopsy;brain disease;brain infarction;brain vasculitis;cancer classification;cancer diagnosis;case report;central nervous system infection;cerebrovascular accident;clinical feature;differential diagnosis;disease association;disease course;female;histopathology;human;lactate dehydrogenase blood level;large cell lymphoma;lymphadenopathy;lymphomatoid granulomatosis;melanoma;mental deterioration;multistage intraparenchymal infarction;neuroimaging;NK T cell lymphoma;nuclear magnetic resonance imaging;progressive multifocal cerebral infarction;sepsis;septic encephalopathy;subacute encephalopathy;undifferentiated carcinoma,"D'Oleo-García, M. C.;Pian, H.;Pascual-Martín, A.;García-Cosio, M.;García-Villanueva, M.",2013,,,0,
4603,Analysis of cerebral lobar microbleeds and a decreased cerebral blood flow in a memory clinic setting,"OBJECTIVE: Cerebral microbleeds (MBs) have been previously associated with cognitive dysfunction, including Alzheimer's disease. In the present study, we aimed to clarify the relationship between cerebral lobar MBs and the regional cerebral blood flow (CBF). METHODS: We investigated the data obtained from 122 patients in our memory clinic who were examined by both MRI and (99m)Tc-ethyl cysteinate dimer (ECD)-single photon emission computed tomography (SPECT). Patient brain scans were superimposed and brain regions containing both decreased CBF and MBs were visually identified. For each patient eight brain regions were evaluated, comprising the right and left frontal, temporal, parietal, and occipital lobes. RESULTS: Cerebral MBs were detected in 36 of the 122 (29.5%) patients. Of these 36 patients, 23 had detectable lobar MBs, which were primarily distributed in the occipital lobe in 19 of the 46 (41.3%) regions with lobar MBs. The frequency of MBs accompanied by a decreased CBF in the parietal and occipital lobes was significantly higher than that observed in the frontal lobe (73.3% vs. 27.3%, p<0.05, and 73.7% vs. 27.3%, p<0.05, respectively). Additionally, a decreased CBF was observed significantly more frequently in the brain regions with 5 or more MBs compared to the regions with one microbleed (83.3 vs. 25.0%, p<0.0005). Among the 17 patients with observable MBs accompanied by a decreased CBF, none were initially diagnosed with either subjective complaints or mild cognitive impairment. CONCLUSION: We determined that the cerebral lobar MBs located in the parietal and occipital lobes, and the lobar regions with a large number of MBs, were significantly more likely to be accompanied by a decreased CBF.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/radionuclide imaging;Cerebrovascular Circulation;Cognition Disorders/*pathology/physiopathology/radionuclide imaging;Cysteine/*analogs & derivatives;Female;Frontal Lobe/*pathology/physiopathology;Humans;Intracranial Hemorrhages/complications/*pathology;Japan;*Magnetic Resonance Imaging;Male;*Organotechnetium Compounds;Reproducibility of Results;*Tomography, Emission-Computed, Single-Photon/methods","Doi, H.;Inamizu, S.;Saito, B. Y.;Murai, H.;Araki, T.;Kira, J.",2015,,10.2169/internalmedicine.54.3747,0,
4604,Fahr's Disease: A Case Report,"Fahr's disease is a rare neuropsychiatric illness characterized by bilateral calcifications of the basal ganglia and white matter. Although its etiology is not yet fully understood, infectious, metabolic and genetic factors have been demonstrated in some cases. Movement disorders, together with dementia and psychiatric symptoms, may be observed as the clinical manifestations of Fahr's disease. In this case report, a 53-year-old male patient who had complaints of skepticism and nervousness was reported. His physical examination revealed signs of dementia. The serum ionized calcium, phosphorus and parathyroid hormone levels were within normal limits. A computed tomography scan of the brain demonstrated bilateral calcifications. © Archives of Neuropsychiatry, published by Galenos Publishing.",quetiapine;adult;article;brain calcification;Brief Psychiatric Rating Scale;case report;computer assisted tomography;dementia;drug dose increase;drug effect;Fahr disease;human;male;Mini Mental State Examination;nervousness;paranoia;physical examination;subdural hematoma,"Doǧan, O.;Meydan, G.;Semiz, M.;Yildirim, O.;Yontar, G.",2011,,,0,
4605,Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer's disease spectrum,"Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer's disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography. The LICA component explaining the largest data variance was highly sensitive to disease severity (AD < MCI < SCI) and revealed widespread coordinated decreases in FA and f1 with increases in all diffusivity measures in AD. Additionally, it reflected regional coordinated decreases and increases in f2, mode and connectivity density, implicating bidirectional alterations of crossing fibers in the fornix, uncinate fasciculi, corpus callosum and major sensorimotor pathways. LICA yielded improved diagnostic classification performance compared to univariate region-of-interest features. Our results document coordinated WM microstructural and connectivity alterations in line with disease severity across the AD continuum.",,"Doan, N. T.;Engvig, A.;Persson, K.;Alnaes, D.;Kaufmann, T.;Rokicki, J.;Cordova-Palomera, A.;Moberget, T.;Braekhus, A.;Barca, M. L.;Engedal, K.;Andreassen, O. A.;Selbaek, G.;Westlye, L. T.",2017,Mar 24,,0,
4606,Predilection role diabetes mellitus and dyslipidemia in the onset of ischemic stroke,"INTRODUCTION: Stroke is the third leading cause of mortality, disability and dementia, but leading cause of epileptic manifestations in the elderly. Diabetes mellitus as permanently elevated blood glucose, often accompanied by dyslipidemia, is among the leading causes of atherosclerotic alteration in blood vessels and is also increasing in the world. GOAL: To determine the existence and predilection of diabetes mellitus and dyslipidemia, in the development of ischemic stroke. MATERIAL AND METHODS: During the 2011 are analyzed all people with stroke admitted at the Neurology Clinic. All patients underwent neurological tests and the laboratory test with special emphasis on the value of blood glucose and lipid levels, with brain CT which confirmed the existence of a stroke, EEG and internist examination. RESULTS: During the one-year period the stroke was confirmed in 1184 patients, aged 33-81 years and 37% in the younger age group (up to 50 yrs.). There was 50.67% male and 49.33% female patients. Ischemic stroke was confirmed in 78.0% (56% with thrombotic and 22% with embolic genesis), of which the 32% was lacunar infarcts (up to 1.5 cm) and hemorrhagic in 22% (SAH in 4.8%, and intracerebral hemorrhage in 17.2%). The most frequent risk factors were hypertension 85%, then smoking in 65%, diabetes mellitus in 39.0%, in 27.38% dyslipidemia, previous stroke in 26.69%, in 23.57% arrhythmia In the baseline sample 30.06% of patients had previously diabetes mellitus and in 8.94% the diabetes was diagnosed during hospitalization, while dyslipidemia was known from earlier in 22.0% and in 5.38% cases was detected during the hospitalization. Among treated patients 79.01% survived, while 20.09% have a fatal outcome. CONCLUSIONS: Diabetes mellitus and dyslipidemia, along with hypertension and smoking are the leading risk factors for the occurrence of stroke. By timely detection and treatment can be controlled slow atherosclerotic changes in blood vessels and thus prevent stroke.","Adult;Aged;Aged, 80 and over;Bosnia and Herzegovina/epidemiology;Brain Ischemia/complications/diagnosis/*epidemiology;Cerebral Hemorrhage/complications/diagnosis/*epidemiology;*Diabetes Complications/blood/drug therapy/epidemiology;Dyslipidemias/complications/diagnosis/*epidemiology;Female;Humans;Hypertension/complications/diagnosis/epidemiology;Hypoglycemic Agents/therapeutic use;Male;Middle Aged;Outcome Assessment (Health Care);Risk Factors;Smoking/adverse effects/epidemiology;*Stroke/epidemiology/etiology/radiography;Treatment Outcome","Djelilovic-Vranic, J.;Alajbegovic, A.;Zelija-Asimi, V.;Niksic, M.;Tiric-Campara, M.;Salcic, S.;Celo, A.",2013,,,0,
4607,Carasil,We herewith report a case of 46 year old male with clinical features suggestive of CARASIL (Cerebral Autosomal Recessive Arteriopathy with Sub cortical Infarcts and Leucoencephalopathy). He had recurrent strokes in early age before reaching 35 years. He was normotensive and had severe degenerative changes in lumbar spine and knee joint on radiographs and had diffuse alopecia. Neuroimaging revealed diffuse hyperintense lesions in cerebral white matter and basal ganglia on mR images. © JAPI.,,"Diwan, A. G.;Bhosle, D. G.;Vikram, A.;Biniwale, A.;Chaudhary, S.;Patodiya, B.",2012,May,,0,
4608,Markers of cerebral small vessel disease and severity of depression in the general population,"The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology.",Anxiety;Cerebral microbleeds;Depressive iisorders;Depressive symptoms;Lacunar infracts;Vascular depression;White matter lesions,"Direk, N.;Perez, H. S.;Akoudad, S.;Verhaaren, B. F.;Niessen, W. J.;Hofman, A.;Vernooij, M. W.;Ikram, M. A.;Tiemeier, H.",2016,Jul 30,10.1016/j.pscychresns.2016.05.002,0,
4609,Anatomic Correlation of the Mini-Mental State Examination: A Voxel-Based Morphometric Study in Older Adults,"The clinical utility of the Mini-Mental State Examination (MMSE) and its shorter version (SMMSE) is still debated. There is a need to better understand the neuroanatomical correlates of these cognitive tests. The objective of this cross-sectional study was to determine whether lower MMSE and SMMSE scores correlated with focal brain volume reduction in older adults. Participants from the GAIT study (n = 207; mean, 70.9+/-5.9 years; 57% female; mean MMSE 26.2+/-3.9; mean SMMSE 5.1+/-1.1) were evaluated using the MMSE and SMMSE and received a 1.5-Tesla MRI scan of the brain. Cortical gray and white matter subvolumes were automatically segmented using Statistical Parametric Mapping. Age, gender, education level, and total intracranial volume were included as potential confounders. We found correlations between the MMSE score and specific cortical regions of the limbic system including the hippocampus, amygdala, cingulate gyrus, and parahippocampal gyrus, independently of the diagnostic category (i.e., mild cognitive impairment or Alzheimer disease or controls). Regarding correlations with the SMMSE score, only one cluster in the left hippocampus was identified, which overlapped with the cluster that was positively correlated with the MMSE score. There were no correlations with the volume of white matter. In conclusion, worse MMSE and SMMSE scores were associated with gray matter atrophy mainly in the limbic system. This finding highlights that atrophy of specific brain regions are related to performance on the MMSE and the SMMSE tests, and provides new insights into the cognitive function probed by these tests.",,"Dinomais, M.;Celle, S.;Duval, G. T.;Roche, F.;Henni, S.;Bartha, R.;Beauchet, O.;Annweiler, C.",2016,,,0,
4610,Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression,"Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment. The biological mechanisms underlying cognitive impairment in LLD are complex and likely involve abnormalities in multiple pathways, or 'cascades,' reflected in specific biomarkers. Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD. To this end, we used a data-driven comprehensive proteomic analysis (multiplex immunoassay including 242 proteins), along with measures of structural brain abnormalities (gray matter atrophy and white matter hyperintensity volume via magnetic resonance imaging), and brain amyloid-beta (Abeta) deposition (PiB-positron emission tomography). We analyzed data from 80 older adults with remitted major depression (36 with mild cognitive impairment (LLD+MCI) and 44 with normal cognitive (LLD+NC)) function. LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis. Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015). We observed no differences in gray matter volume or brain Abeta deposition between groups. Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias). Cognitive impairment in LLD seems to be related to greater cerebrovascular disease along with abnormalities in immune-inflammatory control, cell survival, intracellular signaling, protein and lipid homeostasis, and clotting processes. These results suggest that individuals with LLD and cognitive impairment may be more vulnerable to accelerated brain aging and shed light on possible mediators of their elevated risk for progression to dementia.","Aged;Aged, 80 and over;Benzothiazoles/pharmacokinetics;Biomarkers/ blood;Brain/ pathology/radionuclide imaging;Cognition Disorders/ etiology;Depression/blood/complications/pathology;Female;Humans;Image Processing, Computer-Assisted;Machine Learning;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Positron-Emission Tomography;Proteins/ metabolism;Proteomics/methods;Psychiatric Status Rating Scales","Diniz, B. S.;Sibille, E.;Ding, Y.;Tseng, G.;Aizenstein, H. J.;Lotrich, F.;Becker, J. T.;Lopez, O. L.;Lotze, M. T.;Klunk, W. E.;Reynolds, C. F.;Butters, M. A.",2015,May,10.1038/mp.2014.76,0,
4611,MRI features of pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL),BACKGROUND AND PURPOSE: Cerebral small vessel disease is a topic of growing interest for both the scientific community and the aging society. We report the magnetic resonance imaging (MRI) characteristics of a recently found autosomal dominantly inherited microangiopathy. METHODS: Eighteen members (35 to 77 years) of a large German family underwent MR scanning with a standardized MRI protocol for cerebrovascular diseases. Images were evaluated independently by two neuroradiologists. RESULTS: Six family members revealed an unequivocally pathological phenotype on MRI with lacunar infarcts of the pons (6/6) and lesions of the subcortical and periventricular white matter (5/6). Lesions in the temporal lobes (1/6) and cerebral microbleeds (1/6) were uncommon. None of the patients revealed atherosclerotic changes in MR angiography. Retrospective analysis of 5 brain autopsies from previously reported patients of the same family confirmed the regular involvement of the pons. CONCLUSION: This cerebral autosomal dominant arteriopathy with pontine infarcts and leukoencephalopathy is characterized by a special lesion pattern strikingly different from CADASIL. The distinct MRI characteristics with pontine lesions and rare occurrence of temporal lesions argue for a new nosological entity and may be helpful for the differential diagnosis.,"Adult;Aged;Cerebrovascular Disorders/ genetics/ pathology;Chromosome Disorders/ genetics/ pathology;Dementia, Vascular/ genetics/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Syndrome","Ding, X. Q.;Hagel, C.;Ringelstein, E. B.;Buchheit, S.;Zeumer, H.;Kuhlenbaumer, G.;Appenzeller, S.;Fiehler, J.",2010,Apr,10.1111/j.1552-6569.2008.00336.x,0,
4612,MRI and MRS findings in a patient with infantile neuronal ceroid lipofuscinosis,"A 23-month-old girl of consanguineous parents suffering from infantile neuronal ceroid lipofuscinosis (INCL) was studied with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). A progressive reduction of brain volume was documented in two MRI studies within 2 months. Quantitative measurements of the T2 relaxation times showed a shorter T2 value of the thalamus bilaterally. A reduced concentration of N-acetylaspartate (NAA), and an elevated level of myo-inositol (mI) and lactate (Lac) in white matter were detected by MRS. Differential diagnosis of INCL, rather than Rett syndrome, a disease that evokes a similar clinical syndrome as INCL does, was made mainly based on the MRS data. Absence of the enzyme palmitoyl-protein-thioesterase 1 and a corresponding gene mutation in biochemical studies confirmed INCL.",,"Ding, X.;Lukacs, Z.;Kucinski, T.;Wittkugel, O.;Kilian, D.;Weisz, W.;Kohlschütter, A.;Zeumer, H.",2004,Dec,,0,
4613,"Space and location of cerebral microbleeds, cognitive decline, and dementia in the community","Objective: To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people. Methods: In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementiaunderwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines. Results: In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMBs, participants with 3 CMBs had a steeper decline in a composite measure of global cognitive function, memory, and speed. Among those with 3 deep or mixed CMBs, associations were strongest for memory; the association with speed was strongest in those having 3 strictly lobar CMBs. People with 3 CMBs, regardless of their locations, had a higher incidence of allcause dementia and vascular dementia. Conclusions: Mixed or a higher load of CMBs, with some specificity for location, is associated with accelerated cognitive decline in older people. These findings suggest a role for hypertensive vasculopathy and the combined effect of hypertensive and cerebral amyloid angiopathy in the pathogenesis of cognitive deterioration.",age distribution;aged;article;brain hemorrhage;dementia;disease association;disease marker;female;human;incidence;longitudinal study;major clinical study;male;mental deterioration;microvasculature;multiinfarct dementia;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;practice guideline;prevalence;priority journal;velocity;verbal memory;very elderly,"Ding, J.;Sigurosson, S.;Jónsson, P. V.;Eiriksdottir, G.;Meirelles, O.;Kjartansson, O.;Lopez, O. L.;Van Buchem, M. A.;Gudnason, V.;Launer, L. J.",2017,,10.1212/wnl.0000000000003983,1,
4614,"Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia: The age, gene/environment susceptibility–Reykjavik study","IMPORTANCE: With advancing age, an increased visibility of perivascular spaces (PVSs) on magnetic resonance imaging (MRI) is hypothesized to represent impaired drainage of interstitial fluid from the brain and may reflect underlying cerebral small vessel disease (SVD). However, whether large perivascular spaces (L-PVSs) (>3 mm in diameter) visible on MRI are associated with SVD and cognitive deterioration in older individuals is unknown. OBJECTIVE: To examine whether L-PVSs are associated with the progression of the established MRI markers of SVD, cognitive decline, and increased risk of dementia. DESIGN, SETTING, AND PARTICIPANTS: The prospective, population-based Age, Gene/Environment Susceptibility–Reykjavik Study assessed L-PVSs at baseline (September 1, 2002, through February 28, 2006) on MRI studies of the brain in 2612 participants. Participants returned for additional MRI from April 1, 2007, through September 30, 2011, and underwent neuropsychological testing at the 2 time points a mean (SD) of 5.2 (0.2) years apart. Data analysis was conducted from August 1, 2016, to May 4, 2017. EXPOSURES: The presence, number, and location of L-PVSs. MAIN OUTCOMES AND MEASURES: Incident subcortical infarcts, cerebral microbleeds, and progression of white matter hyperintensities detected on MRI; cognitive decline defined as composite score changes between baseline and follow-up in the domains of memory, information processing speed, and executive function; and adjudicated incident dementia cases diagnosed according to international guidelines. RESULTS: Of the 2612 study patients (mean [SD] age, 74.6 [4.8] years; 1542 [59.0%] female), 424 had L-PVSs and 2188 did not. The prevalence of L-PVSs was 16.2% (median number of L-PVSs, 1; range, 1-17). After adjusting for age, sex, and interval between baseline and follow-up scanning, the presence of L-PVSs was significantly associated with an increased risk of incident subcortical infarcts (adjusted risk ratio, 2.54; 95% CI, 1.76-3.68) and microbleeds (adjusted risk ratio, 1.43; 95% CI, 1.18-1.72) and a greater 5-year progression of white matter hyperintensity volume. The presence of L-PVSs was also associated with a steeper decline in information processing speed and more than quadrupled the risk of vascular dementia. All associations persisted when further adjusted for genetic and cerebrovascular risk factors. The associations with cognitive outcomes were independent of educational level, depression, and other SVD MRI markers. CONCLUSIONS AND RELEVANCE: Large PVSs are an MRI marker of SVD and associated with the pathogenesis of vascular-related cognitive impairment in older individuals. Large PVSs should be included in assessments of vascular cognitive impairment in the older population and as potential targets for interventions.",SignaTwinspeed;aged;article;brain size;cerebrovascular disease;cohort analysis;controlled study;depression;disease association;disease course;female;follow up;human;informed consent;major clinical study;male;memory;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;population research;priority journal;prospective study;scoring system;white matter,"Ding, J.;Sigurðsson, S.;Jónsson, P. V.;Eiriksdottir, G.;Charidimou, A.;Lopez, O. L.;Van Buchem, M. A.;Guðnason, V.;Launer, L. J.",2017,,10.1001/jamaneurol.2017.1397,0,
4615,White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in Community Dwelling Elderly,"BACKGROUND: Unlike western countries, data on white matter hyperintensity (WMH) in community dwelling elderly in Asian population is very limited. OBJECTIVE: To examine the relation between baseline WMH burden and the risk of incident cognitive decline in a community-based cohort with Chinese-dwelling elderly. METHODS: We prospectively evaluated the incident cognitive decline for 226 participants in the Shanghai Aging Study. Baseline WMH severity was visually rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox proportional hazards regression model was used to estimate the relative risk (RR) of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for incident cognitive decline by adjusting potential confounders. RESULTS: Forty subjects were identified with incident cognitive decline (new onset 34 mild cognitive impairment and 6 dementia) during a median duration of 6 years follow-up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2-4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06-1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent predictors of incident cognitive decline. CONCLUSION: Our study demonstrated that confluent WMH may increase the risk of incident cognitive decline by 3 folds in community dwelling subjects. Small vessel disease may cause heavy burden of cognitive impairment in the elderly in China.",Cognitive decline;dementia;mild cognitive impairment;small vessel disease;white matter hyperintensity,"Ding, D.;Xiong, Y.;Zhao, Q.;Guo, Q.;Chu, S.;Chu, W. W. C.;Luo, J.;Liang, X.;Zheng, L.;Hong, Z.;Wong, L. K. S.;Mok, V. C. T.",2018,,,0,
4616,Diffusion tensor imaging (DTI) in the detection of white matter lesions in patients with mild cognitive impairment (MCI),"Mild cognitive impairment (MCI) is recognized as a precursor to dementia. The amnestic MCI progresses usually to Alzheimer disease. Amnestic MCI multiple domain (md-MCI) seems to progress more rapidly than amnestic MCI single domain (a-MCI). In an attempt to identify patients at risk, we examined white matter changes in MCI subtypes using diffusion tensor imaging (DTI). We also tried to correlate DTI findings to neuropsychological tests. Forty-four amnestic single domain (a-MCI) patients, 19 amnestic multi domain (md-MCI), and 25 cognitively normal (NC) controls were included in the present study. All participants were assessed clinically using a battery of cognitive tests. DTI was performed to measure fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Areas studied were corpus callosum, posterior cingulum (PC), anterior cingulum (AC), and superior longitudinal fasciculus (SLF). ADC and FA of the above areas were related to the scores of certain neuropsychological tests that evaluate visual and verbal memory. No difference in DTI measurements was found between the two MCI subtypes. ADC in MCI cases was increased in comparison with NC in the genu, PC, right SLF, and left AC. FA was spared. Verbal memory was related to ADC of the genu, PC, right AC and right SLF, and to FA of the left SLF. Visual memory was related to ADC of the genu, PC, right AC, and SLF. The strongest correlation found was between the visual memory and the ADC of the right PC (Spearman ρ = 0.45, p < 0.001). DTI revealed that ADC was increased in certain brain areas in MCI patients. No difference in DTI measurements was found between the two MCI subtypes. DTI indices correlate with cognitive performance. © 2013 Belgian Neurological Society.",,"Dimitra, S.;Verganelakis, D. A.;Gotsis, E.;Toulas, P.;Papatriantafillou, J.;Karageorgiou, C.;Thomaides, T.;Kapsalaki, E. Z.;Hadjigeorgiou, G.;Papadimitriou, A.",2013,December,,0,
4617,Sensitivity and specificity of 99Tcm-HMPAO single-headed SPECT in dementia,"The sensitivity and specificity of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single-headed single photon emission computed tomography (SPECT) in dementia were evaluated in elderly patients with a mean age of 84 years suffering from dementia (n = 59) and compared to an age- and sex-matched control group with normal cognitive function (n = 14). The demented patients were classified as suffering from primary degenerative dementia (PDD, n = 51) based on DSM-III-R criteria. Moreover, PDD patients were divided into three subgroups of severity of cognitive impairment, according to their Folstein score. Multi-infarct dementia (MID, n = 8) was diagnosed based on clinical features, computed tomographic findings and Hachinski ischaemic score. Images were assessed qualitatively by visual interpretation of shades of colour in cortical regions. A SPECT defect confined to the frontal, parietal, temporal or (parieto) occipital lobe was defined as one lesion. The mean number of SPECT lesions was 1.4 (range 0-4) in the control group, 2.4 (range 0-8) in the PDD group and 2.9 (range 2-5) in the MID group and showed a significant difference (P < 0.02) between groups. To obtain an acceptable level of specificity of 64.3%, a cut-off value of three lesions had to be chosen. In the PDD group, sensitivity was then 25% for the mildly, 43.8% for the moderately and 46.7% for the severely affected PDD subgroup. In the MID group sensitivity was then 75%. Interestingly, in this elderly patient population the location of lesions was homogenously distributed in all groups, including the control group.","Aged;Aged, 80 and over;Dementia/ radionuclide imaging;Dementia, Multi-Infarct/ radionuclide imaging;Female;Humans;Male;Organotechnetium Compounds;Oximes;Sensitivity and Specificity;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Dierckx, R. A.;Vandewoude, M.;Saerens, J.;Hartoko, T.;Marien, P.;Capiau, I.;Vervaet, A.;Dobbeleir, A.;De Deyn, P. P.",1993,Sep,,0,
4618,Cerebral [18F]T807/AV1451 retention pattern in clinically probable CTE resembles pathognomonic distribution of CTE tauopathy,"Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder most commonly associated with repetitive traumatic brain injury (TBI) and characterized by the presence of neurofibrillary tangles of tau protein, known as a tauopathy. Currently, the diagnosis of CTE can only be definitively established postmortem. However, a new positron emission tomography (PET) ligand, [18F] T807/AV1451, may provide the antemortem detection of tau aggregates, and thus various tauopathies, including CTE. Our goal was to examine [18F]T807/AV1451 retention in athletes with neuropsychiatric symptoms associated with a history of multiple concussions. Here we report a 39-year-old retired National Football League player who suffered 22 concussions and manifested progressive neuropsychiatric symptoms. Emotional lability and irritability were the chief complaints. Serial neuropsychological exams revealed a decline in executive functioning, processing speed and fine motor skills. Naming was below average but other cognitive functions were preserved. Structural analysis of longitudinally acquired magenetic resonance imaging scans revealed cortical thinning in the left frontal and lateral temporal areas, as well as volume loss in the basal ganglia. PET with [18F]florbetapir was negative for amyloidosis. The [18F]T807/AV1451 PET showed multifocal areas of retention at the cortical gray matter-white matter junction, a distribution considered pathognomonic for CTE. [18F]T807/AV1451 standard uptake value (SUV) analysis showed increased uptake (SUVr ≥ 1.1) in bilateral cingulate, occipital, and orbitofrontal cortices, and several temporal areas. Although definitive identification of the neuropathological underpinnings basis for [18F]T807/AV1451 retention requires postmortem correlation, our data suggest that [18F]T807/AV1451 tauopathy imaging may be a promising tool to detect and diagnose CTErelated tauopathy in living subjects.",florbetapir f 18;flortaucipir f 18;adult;article;athlete;basal ganglion;brain concussion;brain size;case report;chronic traumatic encephalopathy;cognitive defect;executive function;frontal cortex;gray matter;human;irritability;longitudinal study;male;mental disease;mental instability;motor performance;neuroimaging;nuclear magnetic resonance imaging;tauopathy;temporal cortex;white matter;av 1451,"Dickstein, D. L.;Pullman, M. Y.;Fernandez, C.;Short, J. A.;Kostakoglu, L.;Knesaurek, K.;Soleimani, L.;Jordan, B. D.;Gordon, W. A.;Dams-O'Connor, K.;Delman, B. N.;Wong, E.;Tang, C. Y.;DeKosky, S. T.;Stone, J. R.;Cantu, R. C.;Sano, M.;Hof, P. R.;Gandy, S.",2016,,10.1038/tp.2016.175,0,
4619,Vascular risk factors and progression of white matter hyperintensities in the Lothian Birth Cohort 1936,"We aimed to determine associations between multiple vascular risk factors (VRF) at ~73 years and progression of white matter hyperintensities (WMH) from ~73 years to ~76 years. We calculated correlations and generalized estimating equation models of a comprehensive range of VRF at 73 years and change in WMH volume from 73 years to 76 years. Higher systolic (rho = 0.126, p = 0.009) and diastolic (rho = 0.120, p = 0.013) blood pressure at 73 years were significant predictors for greater WMH volume at 76 years in a simple correlation model. However, neither measured blood pressure nor self-reported hypertension at 73 years was significant predictors of WMH volume change in a fully adjusted model which accounted for initial WMH volume at 73 years. Lower high-density lipoprotein cholesterol (beta = -0.15 % intracranial, -1.80 mL; p < 0.05) and current smoking (beta = 0.43 % intracranial, 5.49 mL; p < 0.05) were the only significant VRF predictors of WMH volume change from 73 years to 76 years. A focus on smoking cessation and lipid lowering, not just antihypertensives, may lead to a reduction in WMH growth in the eighth decade of life.",glycosylated hemoglobin;hemoglobin A1c;high density lipoprotein cholesterol;aged;aging;article;blood pressure measurement;brain size;cardiovascular disease;cohort analysis;controlled study;diabetes mellitus;diastole;diastolic blood pressure;disease course;female;human;hyperlipidemia;hypertension;image processing;major clinical study;male;Mini Mental State Examination;nuclear magnetic resonance imaging;predictor variable;prevalence;priority journal;risk factor;Scotsman;sex difference;smoking;smoking cessation;systole;systolic blood pressure;vascular risk factor;very elderly;white matter hyperintensity;white matter injury,"Dickie, D. A.;Ritchie, S. J.;Cox, S. R.;Sakka, E.;Royle, N. A.;Aribisala, B. S.;Valdés Hernández, M. D. C.;Maniega, S. M.;Pattie, A.;Corley, J.;Starr, J. M.;Bastin, M. E.;Deary, I. J.;Wardlaw, J. M.",2016,,,0,
4620,METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research,"Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.",amyloid;biological marker;anxiety;apathy;Asia;Australia and New Zealand;balance disorder;brain hemorrhage;brain infarction;brain ischemia;brain perfusion;cerebrovascular accident;cognition;cognitive defect;dementia;depression;diffusion tensor imaging;educational status;executive function;gait disorder;human;ICD-10;ICD-11;machine learning;memory;mild cognitive impairment;Mini Mental State Examination;Montreal cognitive assessment;mood disorder;nerve degeneration;neuroimaging;neurologic disease assessment;North America;nuclear magnetic resonance imaging;Parkinson disease;positron emission tomography;priority journal;randomized controlled trial (topic);Rankin scale;risk factor;short survey;small vessel disease;telephone interview of cognitive assessment;transient ischemic attack;vascular disease;vascular lesion;white matter lesion,"Dichgans, M.;Wardlaw, J.;Smith, E.;Zietemann, V.;Seshadri, S.;Sachdev, P.;Biessels, G. J.;Fazekas, F.;Benavente, O.;Pantoni, L.;De Leeuw, F. E.;Norrving, B.;Matthews, P.;Chen, C.;Mok, V.;Düring, M.;Whiteley, W.;Shuler, K.;Alonso, A.;Black, S. E.;Brayne, C.;Chabriat, H.;Cordonnier, C.;Doubal, F.;Duzel, E.;Ewers, M.;Frayne, R.;Hachinski, V.;Ikram, M. A.;Jessen, F.;Jouvent, E.;Linn, J.;O'Brien, J.;van Oostenbrugge, R.;Malik, R.;Mazoyer, B.;Schmidt, R.;Sposato, L. A.;Stephan, B.;Swartz, R. H.;Vernooij, M.;Viswanathan, A.;Werring, D.;Abe, K.;Allan, L.;Arba, F.;Diener, H. C.;Davis, S.;Hankey, G.;Lees, K. R.;Ovbiagele, B.;Weir, C.;Bae, H. J.;Bath, P. M.;Bordet, R.;Breteler, M.;Choi, S.;Deary, I.;DeCarli, C.;Ebmeier, K.;Feng, L.;Greenberg, S. M.;Ihara, M.;Kalaria, R.;Kim, S.;Lim, J. S.;Lindley, R. I.;Mead, G.;Murray, A.;Quinn, T.;Ritchie, C.;Sacco, R.;Al-Shahi Salman, R.;Sprigg, N.;Sudlow, C.;Thomas, A.;van Boxtel, M.;van der Grond, J.;van der Lugt, A.;Yang, Y. H.",2016,,10.1016/j.jalz.2016.06.004,0,
4621,Role of subvoxel free fluid on diffusion parameters in brain tissue with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and its correlation with physical disability: histogram analysis of standard and fluid-attenuated MR diffusion,"BACKGROUND AND PURPOSE: Subcortical signal intensity abnormalities and lacunar infarcts are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. MR diffusion studies reveal abnormalities in lesions and also within normal appearing white matter. To further characterize the underlying pathologic abnormality, we evaluated the role of subvoxel free fluid in brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy on diffusion parameters and physical disability and analyzed the interrelation between diffusion variables and nonlacunar T2 lesion load. METHODS: Mean diffusivity maps from fluid-attenuated and standard diffusion images of 13 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and seven age-matched control participants were compared by means of histogram analysis for three tissue compartments (whole brain parenchyma, normal appearing brain tissue, and nonlacunar lesions) by using a semiautomated region growing algorithm to define whole brain parenchyma and lesions on fluid-attenuated images. RESULTS: In both patients and control participants, the average mean diffusivity of whole brain parenchyma was lower on fluid-attenuated than on standard images (P <.001). Average mean diffusivity and peak location for all compartments were significantly elevated in patients (P <.001) and higher for lesions than for normal appearing brain tissue on both types of images (P <.001). The difference between standard and fluid-attenuated average mean diffusivity of normal appearing brain tissue, reflecting the subvoxel free fluid content, was elevated in patients (P <.05) and correlated closely with the Rankin score (Spearman's rank correlation coefficient = 0.889, P <.001). Average mean diffusivity of whole brain parenchyma and normal appearing brain tissue correlated strongly with the nonlacunar T2 lesion load (Pearson's correlation coefficient = 0.743-0.928, P <.005). CONCLUSION: This study shows that standard diffusion measurements are contaminated by free fluid partial volume effects for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and for control participants. It also provides evidence of a clinical significance of increased subvoxel free fluid in normal appearing brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which may be more important than either global atrophy, increased diffusivity or, T2 lesion load.","Adult;Atrophy;Brain/pathology;Cerebral Infarction/diagnosis/ genetics;Cerebrospinal Fluid/physiology;Chromosome Aberrations;Dementia, Vascular/diagnosis/ genetics;Diffusion;Diffusion Magnetic Resonance Imaging;Disability Evaluation;Female;Genes, Dominant;Humans;Image Enhancement;Image Processing, Computer-Assisted;Male;Mathematical Computing;Mental Status Schedule;Middle Aged;Mutation/genetics;Proto-Oncogene Proteins/genetics;Receptors, Cell Surface;Receptors, Notch;Sensitivity and Specificity","Dichgans, M.;Putz, B.;Boos, D.;Auer, D. P.",2003,Jun-Jul,,0,
4622,The phenotypic spectrum of CADASIL: Clinical findings in 102 cases,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an increasingly recognized autosomal dominant disorder that leads to cerebrovascular manifestations in early adulthood. This study delineates the phenotypic spectrum and the natural history of the disease in 102 affected individuals from 29 families with biopsy-proven CADASIL. Recurrent ischemic episodes (transient ischemic attack [TIA] or stroke) were the most frequent presentation found in 71% of the cases (mean age at onset, 46.1 years; range, 30-66 years; SD, 9.0 years). Forty-eight percent of the cases had developed cognitive deficits. Dementia (28%) was frequently accompanied by gait disturbance (90%), urinary incontinence (86%), and pseudobulbar palsy (52%). Thirty-nine patients (38%) had a history of migraine (mean age at onset, 26.0 years; SD, 8.2 years), which was classified as migraine with aura in 87% of the cases. Psychiatric disturbances were present in 30% of the cases, with adjustment disorder (24%) being the most frequent diagnosis. Ten patients (10%) had a history of epileptic seizures. To delineate the functional consequences of ischemic deficits, we studied the extent of disability in different age groups. The full spectrum of disability was seen in all groups older than age 45. Fifty- five percent of the patients older than age 60 were unable to walk without assistance. However, 14% in this age group exhibited no disability at all. Kaplan-Meier analysis disclosed median survival times of 64 years (males) and 69 years (females). An investigation of the 18 multiplex families revealed marked intrafamilial variations.",adult;aged;artery disease;article;autosomal dominant inheritance;brain artery;brain infarction;clinical observation;cognitive defect;female;genetic analysis;human;leukoencephalopathy;major clinical study;male;multigene family;nuclear magnetic resonance imaging;phenotype;physical disability;priority journal;skin biopsy,"Dichgans, M.;Mayer, M.;Uttner, I.;Brüning, R.;Müller-Höcker, J.;Rungger, G.;Ebke, M.;Klockgether, T.;Gasser, T.",1998,,,0,
4623,Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL,"Background: Cholinergic deficits might contribute to vascular cognitive impairment. Trials of cholinesterase inhibitors in patients with vascular dementia are difficult because of heterogeneous disease mechanisms and overlap between vascular and Alzheimer's disease (AD) pathology in the age-group recruited. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a genetic form of subcortical ischaemic vascular dementia. It represents a homogeneous disease process, and because of CADASIL's early onset, comorbid AD pathology is rare. We did a multicentre, 18-week, placebo-controlled, double-blind, randomised parallel-group trial to determine whether the cholinesterase inhibitor donepezil improves cognition in patients with CADASIL. Methods: 168 patients with CADASIL (mean age 54·8 years) were assigned to 10 mg donepezil per day (n=86) or placebo (n=82) by a computer-generated randomisation protocol. Inclusion criteria included a mini-mental state examination (MMSE) score of 10-27 or a trail making test (TMT) B time score at least 1·5 SD below the mean, after adjustment for age and education. The primary endpoint was change from baseline in the score on the vascular AD assessment scale cognitive subscale (V-ADAS-cog) at 18 weeks. Secondary endpoints included scores on the ADAS-cog, MMSE, TMT A time and B time, Stroop, executive interview-25 (EXIT25), CLOX, disability assessment for dementia, and sum of boxes of the clinical dementia rating scale. Analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00103948. Findings: 161 patients were analysed. There was no significant difference between donepezil (n=84) and placebo (n=77) in the primary endpoint. The least-squares mean change from baseline score was -0·81 (SE 0·59) in the placebo group and -0·85 (SE 0·57) in the donepezil group (p=0·956). There was a significant treatment effect favouring donepezil on the following secondary outcomes: TMT B time (p=0·023), TMT A time (p=0·015), and EXIT25 (p=0·022). Ten donepezil-treated patients discontinued treatment due to adverse events compared to seven placebo-treated patients. Interpretation: Donepezil had no effect on the primary endpoint, the V-ADAS-cog score in CADASIL patients with cognitive impairment. Improvements were noted on several measures of executive function, but the clinical relevance of these findings is not clear. Our findings may have implications for future trial design in subcortical vascular cognitive impairment. Funding: Eisai Medical Research (Ridgefield Park, NJ, USA). © 2008 Elsevier Ltd. All rights reserved.",NCT00103948;anticoagulant agent;anticonvulsive agent;antidepressant agent;antihypertensive agent;antilipemic agent;anxiolytic agent;beta adrenergic receptor blocking agent;calcium channel blocking agent;donepezil;neuroleptic agent;placebo;adult;aged;article;CADASIL;cerebrovascular accident;clinical trial;cognitive defect;controlled clinical trial;controlled study;dementia;diarrhea;dizziness;double blind procedure;drug fatality;drug safety;drug tolerability;drug withdrawal;epilepsy;female;gastrointestinal disease;human;injection site reaction;insomnia;major clinical study;male;mental disease;Mini Mental State Examination;multicenter study;muscle cramp;nausea;neoplasm;nuclear magnetic resonance imaging;patient compliance;priority journal;psychometry;randomized controlled trial;scoring system;transient ischemic attack;vomiting,"Dichgans, M.;Markus, H. S.;Salloway, S.;Verkkoniemi, A.;Moline, M.;Wang, Q.;Posner, H.;Chabriat, H. S.",2008,,,0,
4624,"Letter by Dichgans et al regarding article, ""peripheral Artery Disease as a Manifestation of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and practical implications""",,artery disease;brain damage;CADASIL;cerebrovascular disease;diabetes mellitus;disease severity;heart failure;human;hypotension;letter;nuclear magnetic resonance imaging;peripheral occlusive artery disease;priority journal;risk factor,"Dichgans, M.;Joutel, A.;Chabriat, H.",2013,,,0,
4625,Cerebral microbleeds in CADASIL: A gradient-echo magnetic resonance imaging and autopsy study,"Background and Purpose - An increased frequency of clinically silent microbleeds (MB) has recently been observed in patients with sporadic small-vessel disease related to vascular amyloid deposition or hypertension. In this study, we searched for cerebral MBs in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a unique type of small-vessel disease caused by mutations in the Notch3 gene. Our purposes were (1) to determine the frequency, extent, and pattern of MBs in CADASIL; (2) to analyze the relationship between MBs and T2-hyperintense lesions; and (3) to evaluate the histopathology of brain tissue affected by MBs. Methods - Gradient-echo, T2/PD-weighted dual-echo, and T1-weighted MRI scans of the brain were obtained from 16 consecutive CADASIL subjects and 16 age-matched control subjects. T2-lesion volume measurements were made with a semiautomated segmentation technique based on local thresholding. Postmortem examinations were performed on the brains of 7 additional CADASIL subjects. Results - Focal areas of signal loss on gradient-echo images suggesting past MBs were found in 11 CADASIL individuals (69%) and no control subjects (P<0.001). The average number of MBs was 5.9±7.3 (range, 0 to 22) in individual CADASIL patients. MBs were associated with age (r=0.71, P=0.002) and total lesion volume (r=0.75, P=0.001). However, after correction for age, the correlation with lesion volume was no longer significant. MBs were located simultaneously in various parts of the brain with a preference for cortical-subcortical regions (38%), white matter (20%), thalamus (13%), and brainstem (14%). Eighty-two percent of the MBs were located outside areas appearing hyperintense on T2-weighted images. Postmortem examination revealed focal accumulations of hemosiderin-containing macrophages in 6 of the 7 brains (86%). They were always found outside ischemic lesions. Conclusions - This study shows a high frequency and multiplicity of MBs in individuals with CADASIL. Our results suggest that MBs and ischemic lesions are largely independent manifestations of the underlying angiopathy. The pattern of MBs shows a significant overlap with that reported in other types of small-vessel disease.",,"Dichgans, M.;Holtmannspötter, M.;Herzog, J.;Peters, N.;Bergmann, M.;Yousry, T. A.",2002,2002,,0,
4626,Clinical findings and diagnostic approach in CADASIL,"CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) has been recognised as a surprisingly frequent mendelian condition causing subcortical strokes in young adults. Many patients develop cognitive deficits and eventually become demented. Up to 40% of cases suffer from migraine mostly with aura, and additional manifestations have been mentioned including mood disorders and epileptic seizures. Cerebral magnetic resonance imaging (MRI) reveals diffuse white matter hyperintensities (T(2)-weighted images) in conjunction with small circumscribed infarcts located predominantly within the basal ganglia, the thalamus, the periventricular white matter and the pons. Vascular risk factors are usually absent. Diagnosis may be confirmed both by genetic testing and by ultrastructural examination of skin biopsy samples. Presymptomatic testing requires genetic counseling prior to the test.",,"Dichgans, M.;Gasser, T.",1999,Oct,,0,
4627,Cognition in CADASIL,CADASIL is an early onset small vessel disease and genetic variant of pure subcortical ischemic vascular dementia (SIVD). The condition has been invaluable in defining the profile and neuroimaging correlates of cognitive deficits in pure SIVD. The recent completion of a randomized trial in cognitively impaired CADASIL patients has illustrated the feasibility of targeted therapeutic trials in narrowly defined subtypes of vascular cognitive impairment. This article highlights some of the advances on cognition in CADASIL.,"Brain Infarction/pathology;CADASIL/*physiopathology/*psychology;Cerebral Hemorrhage/pathology;Cognition/*physiology;Cognition Disorders/physiopathology;Dementia, Vascular/physiopathology/psychology;Humans;Magnetic Resonance Imaging","Dichgans, M.",2009,Mar,10.1161/strokeaha.108.534412,0,
4628,CADASIL: A monogenic condition causing stroke and subcortical vascular dementia,"Mutations in Notch3are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited small vessel disease leading to subcortical strokes and vascular dementia. The phenotypic presentation is variable but remarkable for a high frequency of migraine with aura. Magnetic resonance images show a microangiopathic pattern of lesions. Prominent involvement of the temporopolar white matter and involvement of the temporopolar arcuate fibers are conspicuous findings seen in many patients. The underlying angiopathy is characterized by a unique type of ultrastructural basal lamina deposits and by degeneration of vascular smooth muscle cells which are the major source of Notch3 expression. In line with these findings there is evidence for a functional impairment of vascular smooth muscle cells. CADASIL has opened a new perspective in studying basic mechanisms of vessel wall degeneration and ischemic tissue damage related to small vessel disease. Copyright © 2002 S. Karger AG, Basel.",,"Dichgans, M.",2002,2002,,0,
4629,"Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy","Objectives: To describe a severe form of demyelinating HIV-associated leukoencephalopathy in AIDS patients failing highly active antiretroviral therapy (HAART), its relationship to clinical and neuroimaging findings, and suggest hypotheses regarding pathogenesis. Design and methods: AIDS patients who failed HAART and displayed severe leukoencephalopathy were included. All cases had detailed neuromedical, neuropsychological, neuroimaging and postmortem neuropathological examination. Immunocytochemical and PCR analyses were performed to determine brain HIV levels and to exclude other viruses. Results: Seven recent autopsy cases of leukoencephalopathy in antiretroviral-experienced patients with AIDS were identified. Clinically, all were severely immunosuppressed, six (86%) had poorly controlled HIV replication despite combination antiretroviral therapy, and five (71%) had HIV-associated dementia. Neuropathologically, all seven had intense perivascular infiltration by HIV-gp41 immunoreactive monocytes/macrophages and lymphocytes, widespread myelin loss, axonal injury, microgliosis and astrogliosis. The extent of damage exceeds that described prior to the use of HAART. Brain tissue demonstrated high levels of HIV RNA but evidence of other pathogens, such as JC virus, Epstein-Barr virus, cytomegalovirus, human herpes virus type-8, and herpes simplex virus types 1 and 2, was absent. Comparison of the stages of pathology suggests a temporal sequence of events. In this model, white matter damage begins with perivascular infiltration by HIV-infected monocytes, which may occur as a consequence of antiretroviral-associated immune restoration. Intense infiltration by immune cells injures brain endothelial cells and is followed by myelin loss, axonal damage, and finally, astrogliosis. Conclusions: Taken together, our findings provide evidence for the emergence of a severe form of HIV-associated leukoencephalopathy. This condition warrants further study and increased vigilance among those who provide care for HIV-infected individuals. © 2002 Lippincott Williams & Wilkins.",antiretrovirus agent;proteinase inhibitor;RNA directed DNA polymerase inhibitor;virus RNA;acquired immune deficiency syndrome;adult;article;clinical article;dementia;demyelinating disease;female;highly active antiretroviral therapy;human;Human immunodeficiency virus infection;human tissue;immune deficiency;immunohistochemistry;leukoencephalopathy;male;neuropathology;nuclear magnetic resonance imaging;polymerase chain reaction;priority journal;treatment failure;virus replication,"Dianne Langford, T.;Letendre, S. L.;Marcotte, T. D.;Ellis, R. J.;McCutchan, J. A.;Grant, I.;Mallory, M. E.;Hansen, L. A.;Archibald, S.;Jernigan, T.;Masliah, E.",2002,,,0,
4630,Brain atrophy in HIV infection is more strongly associated with CDC clinical stage than with cognitive impairment,"HIV infection often results in MRI-detectable brain atrophy and white matter signal hyperintensities (WMSHs). Magnetic resonance images were obtained from 31 HIV+ male patients and 10 high-risk controls. Variation within the HIV+ group on neuropsychological (NP) impairment and stage of systemic disease were relatively independent, allowing examination of the relative association of MRI measures with NP impairment versus with systemic stage of disease. HIV+ patients compared to high-risk controls evidenced global atrophy, reduced caudate nuclei volume, and a trend to gray matter volume loss but no difference in white matter volume or in WMSHs. These effects were progressive with CDC clinical stage such that patients at CDC stage A had values very close to those of controls, while patients at CDC stage C had the most abnormal values. In contrast, the relationship between these MRI variables and severity of NP impairment was much less dramatic, with the mildly to moderately impaired HIV+ subjects showing MRI volume effects greater than or equal to those of the severely impaired HIV+ subjects. These results suggest that MRI-detectable brain atrophy secondary to HIV infection is not the primary substrate underlying the progressive NP impairment in HIV disease.","AIDS Dementia Complex/classification/ diagnosis;Adult;Atrophy;Bisexuality/psychology;Brain/ pathology;Centers for Disease Control and Prevention (U.S.);HIV Infections/classification/ diagnosis;Homosexuality, Male/psychology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;United States","Di Sclafani, V.;Mackay, R. D.;Meyerhoff, D. J.;Norman, D.;Weiner, M. W.;Fein, G.",1997,May,,0,
4631,New T530C mutation in the aspartoacylase gene caused Canavan disease with no correlation between severity and N-acetylaspartate excretion,"Objective: Canavan disease (OMIM 271900) is a severe autosomal recessive neurodegenerative disorder characterized by spongy degeneration of the brain and caused by mutations in the gene encoding for aspartoacylase (ASPA). The enzyme is responsible for the catalyses of the brain-specific compound N-acetylaspartate (NAA). Design and methods: We report the case of two Egyptian sibling patients suspected of Canavan disease (CD) showing clinical deterioration, white matter degeneration, megalencephaly and severe intellectual impairment. The patients underwent magnetic resonance imaging (MRI) and biochemical analysis of NAA in biological fluid samples (serum and urine). Subsequently, in order to determine the mutation responsible for CD in these two sibs, a molecular biological examination was performed. Results: MRI findings and quantification of high NAA excretion (1378.5 and 680.1. μmol. NAA/mmol. creatinine in urine of 4. months and 4. years old patients, respectively) confirmed the diagnosis of CD and prompted a search for the responsible mutation. The molecular biological analysis revealed homozygosity for the substitution T530C (Ile177Thr) in the exon 4 of the ASPA gene in both sibs.A total loss of enzymatic activity was also recorded. Conclusions: The substitution T530C (Ile177Thr) results in a novel missense mutation causing a CD phenotype with severe clinical characteristics. This mutation was not previously described in the literature. In these two sibs, urinary concentration of NAA appears to correlate inversely to symptom severity and CD progression. © 2013 The Canadian Society of Clinical Chemists.",,"Di Pietro, V.;Cavallari, U.;Amorini, A. M.;Lazzarino, G.;Longo, S.;Poggiani, C.;Cavalli, P.;Tavazzi, B.",2013,December,,0,
4632,Structural MRI investigation of neuroanatomy of corpus callosum in Alzheimer's disease and mild cognitive impairment,"The corpus callosum (CC), which connects the two cerebral hemispheres, is the largest white matter fiber bundle in the human brain. This structure presents a peculiar myelination pattern: it has small diameter fibers, located in the genu, which myelinate much later in normal development, and large diameter fibers of the splenium, which myelinate early in development. Although AD mainly compromise cerebral gray matter structure, there is evidence that white matter may also be involved in the pathology. To illustrate callosal white matter changes in AD pathology, we summarize in vivo MRI imaging studies in humans, focusing on region of interest (ROI), voxel-based morphometry (VBM), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) techniques. Results from the literature showed that changes in the anterior (genu and anterior body) as well as in the posterior (isthmus and splenum) portions of the CC might already be present in the early stages of AD. The spatial (in anterior and posterior callosal subregions) and the temporal (in the early stage of AD) presence of the CC changes support the hypothesis that two mechanisms, Wallerian degeneration and myelin breakdown, might be responsible for the region-specific changes detected in AD patients. Wallerian degeneration affects the posterior CC subregion, which receives axons directly from those brain areas (temporo-parietal lobe regions) primarily affected by the AD pathology. Instead, the myelin breakdown process affects the later-myelinating CC subregion and explains the earlier involvement of the genu in CC atrophy. © 2011 The authors and IOS Press. All rights reserved.",,"Di Paola, M.;Spalletta, G.;Caltagirone, C.",2011,2011,,0,
4633,MRI measures of corpus callosum iron and myelin in early Huntington's disease,"Increased iron in subcortical gray matter (GM) structures of patients with Huntington's disease (HD) has been suggested as a causal factor in neuronal degeneration. But how iron content is related to white matter (WM) changes in HD is still unknown. For example, it is not clear whether WM changes share the same physiopathology (i.e. iron accumulation) with GM or whether there is a different mechanism. The present study used MRI to examine iron content in premanifest gene carriers (PreHD, n = 25) and in early HD patients (n = 25) compared with healthy controls (n = 50). 3T MRI acquisitions included high resolution 3D T1, EPI sequences for diffusion tensor imaging (DTI) as an indirect measure of tissue integrity, and T2*-weighted gradient echo-planar imaging for MR-based relaxometry (R2*), which provides an indirect measure of ferritin/iron deposition in the brain. Myelin breakdown starts in the PreHD stage, but there is no difference in iron content values. Iron content reduction manifests later, in the early HD stage, in which we found a lower R2* parameter value in the isthmus. The WM iron reduction in HD is temporally well-defined (no iron differences in PreHD subjects and iron differences only in early HD patients). Iron level in callosal WM may be regarded as a marker of disease state, as iron does not differentiate PreHD subjects from controls but distinguishes between PreHD and HD.","Adult;Corpus Callosum/ metabolism;Female;Humans;Huntington Disease/metabolism/ pathology;Imaging, Three-Dimensional;Iron/ metabolism;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/ pathology;Psychiatric Status Rating Scales","Di Paola, M.;Phillips, O. R.;Sanchez-Castaneda, C.;Di Pardo, A.;Maglione, V.;Caltagirone, C.;Sabatini, U.;Squitieri, F.",2014,Jul,10.1002/hbm.22391,0,
4634,Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease,"Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology/ psychology;Cognition;Corpus Callosum/ pathology;Depression/ pathology/physiopathology;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Multimodal Imaging;Neuropsychological Tests;Psychiatric Status Rating Scales","Di Paola, M.;Phillips, O.;Orfei, M. D.;Piras, F.;Cacciari, C.;Caltagirone, C.;Spalletta, G.",2015,,10.3233/jad-142895,0,
4635,Callosal atrophy in mild cognitive impairment and Alzheimer's disease: different effects in different stages,"Alzheimer's Disease (AD) is a neurodegenerative disorder that mainly affects grey matter (GM). Nevertheless, a number of investigations have documented white matter (WM) pathology associated with AD. The corpus callosum (CC) is the largest WM fiber bundle in the human brain. It has been shown to be susceptible to atrophy in AD mainly as a correlate of Wallerian degeneration of commissural nerve fibers of the neocortex. The aim of this study was to investigate which callosal regions are affected and whether callosal degeneration is associated with the stage of the disease. For this purpose, we analyzed high-resolution MRI data of patients with amnesic mild cognitive impairment (MCI) (n=20), mild AD (n=20), severe AD (n=10), and of healthy controls (n=20). Callosal morphology was investigated applying two different structural techniques: mesh-based geometrical modeling methods and whole-brain voxel-based analyses. Our findings indicate significant reductions in severe AD patients compared to healthy controls in anterior (genu and anterior body) and posterior (splenium) sections. In contrast, differences between healthy controls and mild AD patients or amnesic MCI patients were less pronounced and did not survive corrections for multiple comparisons. When correlating anterior and posterior WM density of the CC with GM density of the cortex in the severe AD group, we detected significant positive relationships between posterior sections of the CC and the cortex. We conclude that callosal atrophy is present predominantly in the latest stage of AD, where two mechanisms might contribute to WM alterations in severe AD: the Wallerian degeneration in posterior subregions and the myelin breakdown process in anterior subregions.",Aged;Alzheimer Disease/*pathology/psychology;Amnesia/pathology/psychology;Atrophy;Cognition Disorders/*pathology/psychology;Corpus Callosum/*pathology;Disease Progression;Functional Laterality;Humans;Magnetic Resonance Imaging;Neuropsychological Tests,"Di Paola, M.;Luders, E.;Di Iulio, F.;Cherubini, A.;Passafiume, D.;Thompson, P. M.;Caltagirone, C.;Toga, A. W.;Spalletta, G.",2010,Jan 1,10.1016/j.neuroimage.2009.07.050,0,
4636,Multimodal MRI analysis of the corpus callosum reveals white matter differences in presymptomatic and early Huntington's disease,"Recent magnetic resonance imaging (MRI) studies suggest that abnormalities in Huntington's disease (HD) extend to white matter (WM) tracts in early HD and even in presymptomatic stages. Thus, changes of the corpus callosum (CC) may reflect various aspects of HD pathogenesis. We recruited 17 HD patients, 17 pre-HD subjects, and 34 healthy age-matched controls. Three-dimensional anatomical MRI and diffusion tensor images of the brain were acquired on a 3T scanner. Combining region-of-interest analyses, voxel-based morphometry, and tract-based spatial statistics, we investigated callosal thickness, WM density, fractional anisotropy, and radial and axial diffusivities. Compared with controls, pre-HD subjects showed reductions of the isthmus, likely due to myelin damage. Compared with pre-HD subjects, HD patients showed reductions of isthmus and body, with axonal damage confined to the body. Compared with controls, HD patients had significantly decreased callosal measures in extended regions across almost the entire CC. At this disease stage, both myelin and axonal damage are detectable. Supplementary multiple regression analyses revealed that WM reduction density in the isthmus as well as Disease Burden scores allowed to predict the ""HD development"" index. While callosal changes seem to proceed in a posterior-to-anterior direction as the diseases progresses, this observation requires validation in future longitudinal investigations.","Adult;Corpus Callosum/ pathology;Early Diagnosis;Female;Humans;Huntington Disease/ pathology;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Subtraction Technique","Di Paola, M.;Luders, E.;Cherubini, A.;Sanchez-Castaneda, C.;Thompson, P. M.;Toga, A. W.;Caltagirone, C.;Orobello, S.;Elifani, F.;Squitieri, F.;Sabatini, U.",2012,Dec,10.1093/cercor/bhr360,0,
4637,"When, where, and how the corpus callosum changes in MCI and AD: a multimodal MRI study","BACKGROUND: The corpus callosum (CC) has been shown to be susceptible to atrophy in Alzheimer disease (AD) as a correlate of wallerian degeneration or retrogenesis. However, when and where these 2 mechanisms intervene is still unclear. METHODS: In 3 memory clinics, we recruited 38 patients with amnestic mild cognitive impairment (MCI), 38 patients with mild AD, and 40 healthy controls (HC). Combining voxel-based morphometry and diffusion tensor imaging, we investigated CC white matter (WM) density and fractional anisotropy (FA), radial diffusivity (DR), and axial diffusivity (DA). RESULTS: Compared with HC, patients with amnestic MCI showed reduced WM density in the anterior CC subregion; however, FA, DR, and DA did not differ between the 2 groups. Significant changes were found in patients with mild AD compared with HC in the anterior and posterior CC regions. These differences were evident in both voxel-based morphometry and diffusion tensor imaging analyses. Specifically, we found reduced callosal WM density in the genu, posterior body, and splenium; decreased FA and increased DR in the anterior CC subregion; and increased DA, with no difference in the FA, in the posterior CC subregion. CONCLUSIONS: Callosal changes are already present in patients with amnestic mild cognitive impairment (MCI) and mild Alzheimer disease (AD). The precocious involvement of the anterior callosal subregion in amnestic MCI extends to posterior regions in mild AD. Two different mechanisms might contribute to the white matter changes in mild AD: wallerian degeneration in posterior subregions of the corpus callosum (suggested by increased axial diffusivity without fractional anisotropy modifications) and a retrogenesis process in the anterior callosal subregions (suggested by increased radial diffusivity without axial diffusivity modifications).","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Anisotropy;Biomarkers/analysis;Brain Mapping/methods;Cerebral Cortex/ pathology/physiopathology;Cognition Disorders/ pathology/physiopathology;Corpus Callosum/ pathology/physiopathology;Diffusion;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Wallerian Degeneration/pathology/physiopathology","Di Paola, M.;Di Iulio, F.;Cherubini, A.;Blundo, C.;Casini, A. R.;Sancesario, G.;Passafiume, D.;Caltagirone, C.;Spalletta, G.",2010,Apr 6,10.1212/WNL.0b013e3181d7d8cb,0,
4638,What does the corpus callosum tell us about brain changes in the elderly?,"The corpus callosum is the largest hemispheric interconnection bundle in the human brain. Its anterior-posterior fiber caliber gradient can help in understanding the pathophysiological mechanisms underlying white matter changes both in old age and dementia. Here, the Leukoaraiosis and Disability (LADIS) study, a longitudinal cohort study, which shows an association between corpus callosum atrophy and cognitive and motor decline in the elderly, provides the possibility to consider the use of multimodal macro-microstructural imaging of corpus callosum as a marker of structural brain changes of physiological and pathological aging.",,"Di Paola, M.;Caltagirone, C.;Spalletta, G.",2011,Nov,10.1586/ern.11.130,0,
4639,Brain imaging in Kufs disease type B: Case reports,"Background: The clinical traits of Kufs disease (KD) type B (CLN13), an adult-onset neuronal ceroid lipofuscinosis (NCL), are well established according to the neurological features of the cases reported with mutations in CTSF. Case presentation: We hereby report the brain MRI features in two Caucasian women who carried homozygous mutations in CTSF, providing a short review of the neuroradiological findings of other common NCLs. Conclusion: White matter hyperintensities associated with volume reduction of the corpus callosum may be present at the beginning of the behavioural changes in CLN13 and represent further clues for searching mutations in CTSF.",adult;behavior change;brain;case report;Caucasian;corpus callosum;female;human;imaging;mutation;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;white matter;cathepsin F,"Di Fabio, R.;Colonnese, C.;Santorelli, F. M.;Pestillo, L.;Pierelli, F.",2015,,10.1186/s12883-015-0357-6,0,4640
4640,Brain imaging in Kufs disease type B: Case reports,"Background: The clinical traits of Kufs disease (KD) type B (CLN13), an adult-onset neuronal ceroid lipofuscinosis (NCL), are well established according to the neurological features of the cases reported with mutations in CTSF. The neuroradiological characteristics of this uncommon disease have not yet been outlined. Case presentation: We hereby report the brain MRI features in two Caucasian women who carried homozygous mutations in CTSF, providing a short review of the neuroradiological findings of other common NCLs. Together with a brain volume reduction, the two cases showed white matter hyperintensities and thinning of the corpus callosum at onset of the cognitive decline. Conclusion: White matter hyperintensities associated with volume reduction of the corpus callosum may be present at the beginning of the behavioural changes in CLN13 and represent further clues for searching mutations in CTSF.",,"Di Fabio, R.;Colonnese, C.;Santorelli, F. M.;Pestillo, L.;Pierelli, F.",2015,,,0,
4641,A Novel CSF1R Mutation in a Patient with Clinical and Neuroradiological Features of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids,"Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant cerebral white matter degeneration leading to progressive cognitive and motor dysfunction. The peripheral nervous system is generally spared. Recently, mutations in the colony-stimulating factor-1 receptor (CSF1R) gene have been shown to be associated with HDLS. Here we report a new case of HDLS, carrying a mutation in CSF1R and manifesting rapidly progressive dementia and peripheral neuropathy.",beta1a interferon;genomic DNA;immunoglobulin G;methylprednisolone;adult;article;case report;cerebrospinal fluid analysis;cognitive defect;CSF1R gene;dementia;electroencephalography;electromyography;gene;gene mutation;hereditary diffuse leukoencephalopathy with axonal spheroid;human;immunotherapy;leukoencephalopathy;male;multiple sclerosis;neuroimaging;neurologic examination;neuropathy;nuclear magnetic resonance imaging;percutaneous endoscopic gastrostomy;peripheral neuropathy;priority journal;quadriplegia;sequence analysis,"Di Donato, I.;Stabile, C.;Bianchi, S.;Taglia, I.;Mignarri, A.;Salvatore, S.;Giorgio, E.;Brusco, A.;Simone, I.;Dotti, M. T.;Federico, A.",2015,,,0,
4642,Heterozygous mutations of HTRA1 gene in patients with familial cerebral small vessel disease,"AIMS: Cerebral small vessel disease (SVD) is the leading cause of vascular dementia. Although the most of cases are sporadic, familial monogenic causes have been identified in a growing minority of patients. CADASIL, due to mutations of NOTCH3 gene, is the most common genetic SVD, and CARASIL, linked to HTRA1 gene mutations, is a rare but well known autosomal recessive SVD. Recently, also heterozygous HTRA1 mutations have been described in patients with familial SVD. To detect a genetic cause of familial SVD, we performed mutational analysis of HTRA1 gene in a large cohort of Italian NOTCH3-negative patients. METHODS: We recruited 142 NOTCH3-negative patients and 160 healthy age-matched controls. Additional control data were obtained from five pathogenicity prediction software. RESULTS: Five different HTRA1 heterozygous mutations were detected in nine patients from five unrelated families. Clinical phenotype was typical of SVD, and the onset was presenile. Brain magnetic resonance imaging (MRI) showed a subcortical leukoencephalopathy, with involvement of the external and internal capsule, corpus callosum, and multiple lacunar infarcts. Cerebral microbleeds were also seen, while anterior temporal lobes involvement was not present. CONCLUSION: Our observation further supports the pathogenic role of the heterozygous HTRA1 mutations in familial SVD.",Htra1;Notch3;Cadasil;Carasil;small vessel disease,"Di Donato, I.;Bianchi, S.;Gallus, G. N.;Cerase, A.;Taglia, I.;Pescini, F.;Nannucci, S.;Battisti, C.;Inzitari, D.;Pantoni, L.;Zini, A.;Federico, A.;Dotti, M. T.",2017,Sep,,0,
4643,Magnetic resonance of the encephalon in 17 patients with ocular Behçet's disease,"Behçet's disease is a chronic relapsing disorder of unknown etiology characterized by oral aphthous ulcerations, uveitis, genital ulcerations and bone lesions. A variety of other signs including polyarthritis, vascular conditions (blood vessel occlusions and aneurysms), epididymitis, gastrointestinal, pulmonary and heart lesions may also occur. Central nervous system (CNS) involvement is reported in 10-49% of cases and it is the first symptom of the disease in 5% of subjects. The neuro-Behçet's syndrome may appear as a brainstem syndrome, meningoencephalitis and an organic confusional syndrome or dementia. Cranial hypertension, mostly related to cerebral venous thrombosis, is also present in neuro-Behçet's disease and its incidence is reported in up to 10% of Behçet's patients. MRI is reportedly the most sensitive neuroradiologic approach to detect the focal lesions related to neuro-Behçet's disease and several single cases or series of Behçet's patients with neurologic signs have been examined with MRI. We used MRI to investigate CNS involvement in Behçet's disease patients with and without previous neurologic signs. MRI was carried out on 17 patients with ocular Behçet's disease without neurologic symptoms to assess the possible subclinical involvement of the CNS. Cerebrospinal fluid spaces were enlarged in 8 patients and 5 patients exhibited cortical atrophy. PD and T2-weighted hypersignal foci were demonstrated in parietal, frontal, subcortical and periventricular white matter in 6 subjects. Neuroradiologic abnormalities were found only in the patients with complete disease and with the disease diagnosed more than 10 years earlier. Even though the pathogenesis of these neuroradiologic abnormalities and their correlation with Behçet's disease remain to be clarified, our study suggests the possibility of subclinical CNS involvement in these patients, which may affect the therapeutic approach and their prognosis.",adolescent;adult;aged;article;Behcet disease;brain disease;child;clinical trial;eye disease;female;human;male;middle aged;nuclear magnetic resonance imaging;pathology,"Di Biasi, C.;Accorinti, M.;Trasimeni, G.;Pivetti Pezzi, P.;Melone, A.;Gualdi, G.",1997,,,0,
4644,An unusual case of cortical blindness,"A young female, ten days post-partum, presented with features of bilateral cortical blindness, left-sided hemiparesis, bladder incontinence, confusion, inability to distinguish right from left, acalculia, alexia and agraphia. CT scan and MRI of the brain confirmed infarction of both parieto-occipital lobes. VEP showed increased latency. Other investigations like ESR, APLA and echocardiography was found to be normal. The patient had an ambiguous history of treatment of hypertensive encephalopathy one week prior to delivery, but there was no history of eclampsia or significant intra/post-partum haemorrhage. After five months follow-up, hemiparesis and other neurological signs have improved without any change in the visual status. This is a rare, established case of cortical blindness and Gerstmann's Syndrome without any clue regarding its aetilogy.",adult;agraphia;alexia;article;brain infarction;case report;cerebral blindness;computer assisted tomography;confusion;delivery;disease association;disorientation;female;follow up;Gerstmann Straussler Scheinker syndrome;hemiparesis;human;hypertension encephalopathy;neurologic disease;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;puerperium;urine incontinence,"Dey, A.;Chattopadhyay, S.;Dhar, S.",2001,,,0,
4645,Toward a definite diagnosis of Alzheimer's disease,"There is a significant, and growing, number of patients who suffer from dementia of the Alzheimer's type (DAT). However, due to clinical variability and symptom overlap, and despite millions of dollars spent in diagnostic work-ups, the diagnosis of DAT remains one of exclusion or by neuropathologic study (usually postmortem). This report evaluates two promising methods, the newly refined clinical criteria sets (e.g., NINCDS-ADRDA) and single-photon emission computed tomography (SPECT), on their capacity for definite, accurate, and early diagnosis of DAT patients. We found that clinical diagnosis of DAT can achieve a weighted average for sensitivity of 72%, specificity of 86%, and diagnostic confidence of 72%; however, when NINCDS- ADRDA criteria are used, these results improve to 88%, 91%, and 92%, respectively. SPECT scans could differentiate DAT patients from normals with 86% sensitivity, 96% specificity, and 98% diagnostic confidence. Comparable figures for DAT versus multi-infarct dementia (MID) are 82%, 81%, and 86%, respectively. We conclude that, although a definite clinical diagnosis of DAT is still elusive and more research is needed, the use of either NINCDS-ADRDA criteria or SPECT scans may enhance diagnostic accuracy.",3 quinuclidinyl 4 iodobenzilate;diamine;hexamethylpropylene amine oxime technetium tc 99m;iofetamine i 123;radiopharmaceutical agent;xenon 133;Alzheimer disease;article;blood brain barrier;brain blood flow;computer assisted tomography;diagnostic accuracy;diagnostic procedure;differential diagnosis;disease severity;human;Huntington chorea;intermethod comparison;multiinfarct dementia;neurofibrillary tangle;nuclear magnetic resonance imaging;Parkinson disease;reliability;senile plaque;single photon emission computer tomography,"Dewan, M. J.;Gupta, S.",1992,,,0,
4646,Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F 18,"Background: Alzheimer's disease (AD) is characterized by beta-amyloid plaques (Abeta) and tau neurofibrillary tangles (NFTs). There are several PET imaging biomarkers for Abeta including (11)C-PiB and (18)F florbetapir. Recently, PET tracers for tau NFTs have become available and have shown utility in detection and monitoring of neurofibrillary pathology over time. Flortaucipir F 18 is one such tracer. Initial clinical studies indicated greater tau binding in AD and MCI patients compared to controls in a pattern consistent with tau pathology observed at autopsy. However, little is known about the reproducibility of such findings. This study reports the first data regarding test-retest reproducibility of flortaucipir PET. Methods: Twenty-one subjects who completed the study (5 healthy control, 6 MCI, and 10 AD) received 370 MBq flortaucipir and were imaged for 20 min beginning 80 min after injection and again at 110 min after injection. Follow-up (retest) imaging occurred between 48 hr and 4 weeks after initial imaging. Images were spatially normalized to MNI template space. SUVr values were calculated using AAL VOIs for parietal, temporal, occipital, anterior and posterior hippocampal, parahippocampal and fusiform regions, as well as a posterior neocortical VOI composed of average values from parietal, temporal and occipital areas. Further, a VOI derived by discriminant analysis that maximally separated diagnostic groups (MUBADA) was employed. All VOIs were referenced to a sub-section of cerebellum gray matter (cerebellar crus) as well as a parametrically-derived white-matter based reference region (PERSI). T-tests, correlation analyses and intra-class correlation coefficient (ICC) were used to explore test-retest performance. Results: Test-retest analyses demonstrated low variability in flortaucipir SUVR. The standard deviation of mean percent change between test and retest using the PERSI reference region was 2.22% for a large posterior neocortical VOI, 1.84% for MUBADA, 1.46% for frontal, 1.98% for temporal, 2.28% for parietal and 3.27% for occipital VOIs. Further, significant correlations (R2>0.85; p<0.001) were observed for all regions and ICC values (test-retest consistency) were >0.92 for all regions. Conclusion: Significant test-retest reproducibility for flortaucipir was found across neocortical and mesial temporal lobe structures. These preliminary data suggest that flortaucipir tau imaging could be used to examine changes in tau burden over time.",Av-1451;Alzheimers disease;Neurology;Pet;Radiopharmaceuticals;flortaucipir;reliability;tau imaging,"Devous, M. D., Sr.;Joshi, A. D.;Navitsky, M.;Southekal, S.;Pontecorvo, M. J.;Shen, H.;Lu, M.;Shankle, W. R.;Seibyl, J. P.;Marek, K.;Mintun, M. A.",2017,Dec 28,,0,
4647,Do cerebral white matter lesions influence the rate of progression from mild cognitive impairment to dementia?,"BACKGROUND: Cerebral white matter lesions (WML), evident on CT and MRI brain scans, are histopathologically heterogeneous but associated with vascular risk factors and thought mainly to indicate ischemic damage. There has been disagreement over their clinical prognostic value in predicting conversion from mild cognitive impairment (MCI) to dementia. METHODS: We scrutinised and rated CT and MRI brain scans for degree of WML in a memory clinic cohort of 129 patients with at least 1 year of follow-up. We examined the relationship between WML severity and time until conversion to dementia for all MCI patients and for amnestic (aMCI) and non-amnestic (naMCI) subgroups separately. RESULTS: Five-year outcome data were available for 87 (67%) of the 129 patients. The proportion of patients converting to dementia was 25% at 1 year and 76% at 5 years. Patients with aMCI converted to dementia significantly earlier than those with naMCI. WML severity was not associated with time to conversion to dementia for either MCI patients in general or aMCI patients in particular. Among naMCI patients, there was a tendency for those with a low degree of WML to survive without dementia for longer than those with a high degree of WML. However, this was not statistically significant. CONCLUSIONS: MCI subtype is a significant independent predictor of conversion to dementia, with aMCI patients having higher risk than naMCI for conversion throughout the 5-year follow-up period. WML severity does not influence conversion to dementia for aMCI but might accelerate progression in naMCI.","Aged;Cerebral Cortex/*pathology/radiography;Dementia/*pathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/*pathology;Neuroimaging;Retrospective Studies;Tomography, X-Ray Computed","Devine, M. E.;Fonseca, J. A.;Walker, Z.",2013,Jan,10.1017/s1041610212000932,0,
4648,Cerebral white matter changes and rate of progression of dementia during cholinesterase inhibitor treatment: a retrospective cohort study,"BACKGROUND: Cerebral white matter changes (WMC) represent cerebrovascular disease (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies (DLB). Predictors of treatment response are controversial. OBJECTIVE: To investigate the effect of WMC severity on rate of progression of dementia during treatment with ChEIs. METHODS: CT or MRI brain scans were rated for WMC severity in 243 patients taking ChEIs for dementia. Raters were blind to patients' clinical risk factors, dementia subtype and course of illness. Effects of WMC severity on rates of decline in cognition, function and behaviour were analysed for 140 patients treated for 9 months or longer. Analysis was performed for this group as a whole and within diagnostic subgroups AD and DLB. The main outcome measure was rate of change in Mini Mental State Examination (MMSE) score. Secondary measures were rates of change in scores on the Cambridge Cognitive Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton Assessment Procedures for the Elderly - Behaviour Rating Scale (CAPE-BRS). RESULTS: There was no significant association between severity of WMC and any specified outcome variable for the cohort as a whole or for patients with AD. In patients with DLB, higher WMC scores were associated with more rapid cognitive decline. CONCLUSIONS: Increased WMC severity does not influence clinical response to ChEI treatment in AD, but may hasten deterioration in ChEI-treated patients with DLB.","Aged;Aged, 80 and over;Brain/*pathology;Cholinesterase Inhibitors/*therapeutic use;Cognition Disorders/etiology/pathology/prevention & control;Dementia/*drug therapy/*pathology/psychology;Disease Progression;Female;Follow-Up Studies;Geriatric Assessment/methods;Humans;Magnetic Resonance Imaging;Male;Psychiatric Status Rating Scales;Retrospective Studies;Tomography, X-Ray Computed;Treatment Outcome","Devine, M. E.;Fonseca, J. A.;Walker, R. W.;Sikdar, T.;Stevens, T.;Walker, Z.",2007,Nov,10.1002/gps.1799,0,
4649,Olfactory identification deficits and MCI in a multi-ethnic elderly community sample,"Odor identification deficits occur in Alzheimer's disease (AD) and mild cognitive impairment (MCI), and predict clinical conversion from MCI to AD. In an epidemiologic study conducted in a multi-ethnic community elderly sample (average 80 years old), the University of Pennsylvania Smell Identification Test (UPSIT, range 0-40) was administered to 1092 non-demented subjects. Women (mean 26.6, S.D. 6.6) scored higher than men (mean 24.4, S.D. 7.4, p<.02), and ethnic differences were not significant after controlling for age and education. UPSIT scores correlated inversely with age (r=-0.24, p<.0001) and positively with Selective Reminding Test immediate recall (r=0.33), delayed recall (r=0.28), category fluency (r=0.28) and the 15-item Boston Naming Test (r=0.23), all ps<.0001. In a sub-sample in which MRI was done, UPSIT scores showed a significant correlation with hippocampal volume (n=571, r=0.16, p<.001) but not entorhinal cortex volume nor total number of white matter hyperintensities. In ANOVA, UPSIT scores differed (p<.0001) as a function of MCI classification: no MCI (mean 26.6, S.D. 6.8), non-amnestic MCI (mean 24.4, S.D. 7.2), and amnestic MCI (mean 23.5, S.D. 6.7). The difference between amnestic MCI and no MCI remained significant after controlling for relevant covariates. These findings indicate that the predictive utility of olfactory identification deficits for decline from no MCI to MCI and AD needs to be assessed in longitudinal studies of elderly community samples.","Aged, 80 and over;Cognition Disorders/*ethnology;Comorbidity;Female;Humans;Male;New York/epidemiology;Olfaction Disorders/*ethnology;Prevalence;Risk Assessment;Risk Factors","Devanand, D. P.;Tabert, M. H.;Cuasay, K.;Manly, J. J.;Schupf, N.;Brickman, A. M.;Andrews, H.;Brown, T. R.;DeCarli, C.;Mayeux, R.",2010,Sep,10.1016/j.neurobiolaging.2008.09.008,0,
4650,"CADASIL in a North American Family: Clinical, pathologic, and radiologic findings","Objective: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Background: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. Method: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. Results: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. Conclusions: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.",brain protein;Notch3 receptor;unclassified drug;adult;article;brain infarction;case report;dementia;genetic risk;histopathology;human;human cell;human tissue;leukoencephalopathy;male;neuropsychological test;phenotype;priority journal;protein determination,"Desmond, D. W.;Moroney, J. T.;Lynch, T.;Chan, S.;Chin, S. S.;Shungu, D. C.;Naini, A. B.;Mohr, J. P.",1998,,,0,
4651,Cognition and white matter lesions,"Although it is recognized that ischemic stroke is a potent risk factor for vascular dementia, the influence of white matter lesions (WML) on cognitive function is less clear. In community-based MRI studies that have administered mental status tests to subjects who were free of clinically evident neurologic disease, a weak relationship between WML and generalized cognitive function has been reported. In studies that have administered neuropsychological test batteries, a stronger and more specific association has been recognized between WML and deficits in executive function, most likely due to the involvement of frontal-subcortical pathways. Cognitive deficits may be related to the total volume of the WML, with a threshold perhaps needing to be surpassed before such deficits are evident, but it is likely that the location of the WML also plays a role, with that threshold varying in association with the distribution of the lesions. Potential confounders of the results of previous studies include small, strategically located subcortical infarctions that may be masked by more extensive WML and other comorbid neurologic disorders, particularly Alzheimer's disease. Future studies should be prospective, utilize standardized methods for structural and functional brain imaging, and administer comprehensive neuropsychological assessments in order to more rigorously investigate the relationship between evolving WML and declining cognitive functions. Copyright © 2002 S. Karger AG, Basel.",,"Desmond, D. W.",2002,2002,,0,
4652,Cerebral lacunae: Still a matter of debate,"During the last fifteen years, a new interest has been shown in cerebral lacunes due to the development of brain imagery using Magnetic Resonance Imaging (MRI). The concept of lacunar infarction as defined par Fisher (lacunar hypothesis) can no longer be accepted. Clinical data showed that the so-called lacunar clinical syndromes were far from being specific and could be observed in corticosubcortical infarcts. Epidemiological data pointed out that hypertensive disease was not found in many cases of lacunar infarction. Pathological studies suggest that there are two types of lacunar infarction. Lacunar infarcts resulting in clinical stroke syndromes (type 1 a lacunae) seem to be mainly due to obstruction of the trunk of a perforating artery by atherosclerosis. Silent lacunar infarcts (type 1 b lacunae) result from obstruction of small ramifications of the perforating arteries by a non specific microangiopathy related to age, atherosclerosis, cardiovascular disease as well as to hypertensive disease. Silent lacunar infarcts and dilatation of perivascular spaces (type 3 lacunae) are associated with the white matter hyperintensities shown by MRI in elderly subjects. Lacunar infarcts and diffuse white matter hyperintensities are related to small vessel changes and ischaemic damages resulting from (a) arteriolar occlusion and or (b) loss of autoregulation associated with variations in systemic blood pressure. Both lesions constitute a high risk to develop Vascular Cognitive Impairment (Hachinski) and are frequently associated with Alzheimer's disease. Cases of giant or expanding type 3 lacunae have been reported in the last ten years but the physiopathology of such lacunes and their relationship with clinical symptoms remain a puzzle.",,"Derouesné, C.;Poirier, J.",1999,1999,,0,
4653,Mental changes in subcortical arteriosclerotic encephalopathy,"We describe six patients with chronic hypertension, atherosclerotic vascular disease and periventricular leukoencephalopathy (PVL) on CT. PVL was combined with cortical infarcts in one and with lacunar infarcts in five patients. On neuropsychological examination all patients showed the characteristic features of a subcortical type of mental deterioration. Clinico-radiologic correlation suggests a direct association of PVL and subcortical dementia, and it is argued that prominent cortical features in the dementia of patients with vascular disease and PVL suggest the concomitant presence of Alzheimer's disease.","Aphasia/diagnosis;Cerebral Infarction/diagnosis;Dementia/*diagnosis/psychology;Humans;Intracranial Arteriosclerosis/*diagnosis/psychology;Leukoencephalopathy, Progressive Multifocal/*diagnosis;*Neuropsychological Tests;Reflex, Abnormal/diagnosis;Tomography, X-Ray Computed","Derix, M. M.;Hijdra, A.;Verbeeten, B. W., Jr.",1987,,,0,
4654,Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) in Two Siblings with Neuropsychiatric Symptoms,,biperiden;cyanocobalamin;escitalopram;neuroleptic agent;Notch3 receptor;quetiapine;risperidone;sertraline;steroid;adult;amnesia;anger;anhedonia;article;auditory hallucination;Babinski reflex;behavior disorder;CADASIL;case report;cerebrovascular accident;cognitive defect;confusion;corticosteroid therapy;dementia;depression;diagnostic imaging;drug substitution;drug treatment failure;dysarthria;exon;family history;fatigue;female;genetic screening;headache;human;insomnia;intestine function disorder;irritability;major depression;male;memory disorder;mental disease;missense mutation;neuroimaging;nuclear magnetic resonance imaging;pain;sibling;treatment response;urinary dysfunction;visual hallucination;vitamin supplementation,"Dericioglu, N.;Vural, A.;Agayeva, N.;Basar, K.;Anil Yagcioglu, A. E.;Gursoy-Ozdemir, Y.",2013,,,0,
4655,Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis,"OBJECTIVE: White matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant. METHODS: In total, 95 participants were enrolled: 30 patients with early and advanced relapsing-remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS). RESULTS: 29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P < 10(- 10)), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R = 0.62, P = 0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD. CONCLUSION: Whole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV-cortex disproportionality and allows us to assess ""pure"" WMA without being confounded by intracranial volume. WMA seems to be a characteristic symptom in early MS and can already occur in patients with CIS and should thus be considered in future MS research and clinical studies.","Adolescent;Adult;Aged;Alzheimer Disease/ pathology;Anisotropy;Atrophy;Case-Control Studies;Cerebral Cortex/ pathology;Demyelinating Diseases/ pathology;Female;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Multiple Sclerosis/ pathology;White Matter/ pathology;Young Adult","Deppe, M.;Marinell, J.;Kramer, J.;Duning, T.;Ruck, T.;Simon, O. J.;Zipp, F.;Wiendl, H.;Meuth, S. G.",2014,,10.1016/j.nicl.2014.02.012,0,
4656,Diffusion-tensor imaging at 3 T: detection of white matter alterations in neurological patients on the basis of normal values,"OBJECTIVE: Fractional anisotropy (FA) is a powerful measure to study the integrity of the cerebral white matter in vivo. However, because clinical FA assessments are frequently based on single slice evaluations, intra- and interindividual comparisons are highly dependent on image alignment. We attempted to develop an observer-independent, fully automated technique for quantitative FA assessment. MATERIALS AND METHODS: We employed whole brain diffusion tensor imaging at 3 T with an echo planar imaging sequence (isotropic spatial resolution 1.8 mm) on 4 patients (2x Alzheimer disease, 1x microangiopathy, 1x paraneoplastic disease) and 2 normal control groups (group ""young,"" age 19-32 years; group ""old,"" age 59-69 years). The images were spatially normalized to the standard brain template of the Montreal Neurologic Institute. We introduced a fractional anisotropy index (FAI) as a single measure for the mean tissue anisotropy in certain brain regions of interest. The regions of interest were defined by masks in relation to the Montreal Neurologic Institute coordinate space. We varied the spatial extent of the masks. Confidence intervals of the FAIs for both control groups were calculated. RESULTS: We found the resulting FAIs to be highly robust against considerable mask variations (product-moment correlation: r > 0.97). The FAIs of the 4 patients presented with neurologic conditions associated with white matter alterations significantly fell outside the confidence intervals for normal FA. CONCLUSION: FAIs based on mean fractional anisotropy values obtained from isotropic whole-head high-field diffusion tensor imaging by fully automated algorithms represent a robust and observer-independent measure for the comparative assessment of white matter integrity, ideally suited for further statistical treatments.","Adult;Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/pathology;Anisotropy;Brain Mapping/ methods;Cerebrovascular Disorders/pathology;Diffusion Magnetic Resonance Imaging/ methods;Echo-Planar Imaging;Female;Humans;Male;Microcirculation;Middle Aged;Paraneoplastic Syndromes, Nervous System/pathology;Reference Values","Deppe, M.;Duning, T.;Mohammadi, S.;Schwindt, W.;Kugel, H.;Knecht, S.;Ringelstein, E. B.",2007,Jun,10.1097/01.rli.0000261935.41188.39,0,
4657,Learning-based 3T brain MRI segmentation with guidance from 7T MRI labeling,"PURPOSE: Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods. Recent advances in ultrahigh field 7T imaging make it possible to acquire images with excellent intensity contrast and signal-to-noise ratio. METHODS: In this paper, the authors propose an algorithm based on random forest for segmenting 3T MR images by training a series of classifiers based on reliable labels obtained semiautomatically from 7T MR images. The proposed algorithm iteratively refines the probability maps of WM, GM, and CSF via a cascade of random forest classifiers for improved tissue segmentation. RESULTS: The proposed method was validated on two datasets, i.e., 10 subjects collected at their institution and 797 3T MR images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Specifically, for the mean Dice ratio of all 10 subjects, the proposed method achieved 94.52% +/- 0.9%, 89.49% +/- 1.83%, and 79.97% +/- 4.32% for WM, GM, and CSF, respectively, which are significantly better than the state-of-the-art methods (p-values < 0.021). For the ADNI dataset, the group difference comparisons indicate that the proposed algorithm outperforms state-of-the-art segmentation methods. CONCLUSIONS: The authors have developed and validated a novel fully automated method for 3T brain MR image segmentation.","Adult;Algorithms;Alzheimer Disease/diagnostic imaging;Brain/ diagnostic imaging;Female;Humans;Image Processing, Computer-Assisted/ methods;Machine Learning;Magnetic Resonance Imaging;Male;Signal-To-Noise Ratio;7T MRI labeling;Artificial neural networks;Biological material, e.g. blood, urine;Haemocytometers;Brain;Digital computing or data processing equipment or methods, specially adapted for;specific applications;Image data processing or generation, in general;Involving electronic [emr] or nuclear [nmr] magnetic resonance, e.g. magnetic;resonance imaging;Learning;Medical image contrast;Medical image segmentation;Medical magnetic resonance imaging;Tissues;biomedical MRI;brain MRI;diseases;high magnetic field;image segmentation;medical image processing;pattern classification;segmentation","Deng, M.;Yu, R.;Wang, L.;Shi, F.;Yap, P. T.;Shen, D.;Alzheimer's Disease Neuroimaging, Initiative",2016,Dec,,0,
4658,Diffusion tensor imaging reveals white matter changes associated with cognitive status in patients with Parkinson's disease,"Objective: Cognitive deficit and white matter alteration relationships in Parkinson's disease (PD) were investigated. Methods: Comparison of 64 patients with PD (M:F, 34:30; 64.4 + 10.4 years) classified as cognitively normal (PD-CogNL, n = 24), mild cognitive impairment (PD-MCI, n = 30), and dementia (PD-D, n = 10) with 21 healthy participants (M:F, 10:11; 60.1+13.6 years) was conducted using white matter fractional anisotropy (FA), region-of-interest analysis, and diffusion tensor imaging. Results: The PD-D and PD-MCI exhibited higher Unified Parkinson's Disease Rating Scale motor scores (P < .001; P < .01) and Hoehn-Yahr stages (P < .001; P < .05) and FA reductions in left frontal/right temporal white matter and bilateral anterior cingulated bundles. Largest FA reductions occurred in PD-D left anterior cingulated bundle and corpus callosum splenium. Disease durations of PD-D = 6.8+6.86, PD-MCI = 5.1+2.9, and PD-CogNL = 4.7+3.4 years, suggesting progressive deterioration. Conclusions: Cerebral white matter deterioration may underlie progressive cognitive impairment in PD. © The Author(s) 2012.",,"Deng, B.;Zhang, Y.;Wang, L.;Peng, K.;Han, L.;Nie, K.;Yang, H.;Zhang, L.;Wang, J.",2013,March,,0,
4659,Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI,"AIM/HYPOTHESIS: Type 2 diabetes increases the risk not only of vascular dementia but also of Alzheimer's disease. The question remains whether diabetes increases the risk of Alzheimer's disease by diabetic vasculopathy or whether diabetes influences directly the development of Alzheimer neuropathology. In vivo, hippocampal and amygdalar atrophy on brain MRI are good, early markers of the degree of Alzheimer neuropathology. We investigated the association between diabetes mellitus, insulin resistance and the degree of hippocampal and amygdalar atrophy on magnetic resonance imaging (MRI) accounting for vascular pathology. METHODS: Data was obtained in a population-based study of elderly subjects without dementia between 60 to 90 years of age. The presence of diabetes mellitus and, in non-diabetic subjects, insulin resistance was assessed for 506 participants in whom hippocampal and amygdalar volumes on MRI were measured. We assessed the degree of vascular morbidity by rating carotid atherosclerosis, and brain white matter lesions and infarcts on MRI. RESULTS: Subjects with diabetes mellitus had more hippocampal and amygdalar atrophy on MRI compared to subjects without diabetes mellitus. Furthermore, increasing insulin resistance was associated with more amygdalar atrophy on MRI. The associations were not due to vascular morbidity being more pronounced in persons with diabetes mellitus. CONCLUSIONS/INTERPRETATION: Type 2 diabetes is associated with hippocampal and amygdalar atrophy, regardless of vascular pathology. This could suggest that Type 2 diabetes directly influences the development of Alzheimer neuropathology.","Aged;Atrophy;Carotid Stenosis/epidemiology;Diabetes Mellitus, Type 2/ pathology;Diabetic Angiopathies/epidemiology;Female;Hippocampus/anatomy & histology/pathology;Humans;Magnetic Resonance Imaging;Male;Temporal Lobe/ pathology","den Heijer, T.;Vermeer, S. E.;van Dijk, E. J.;Prins, N. D.;Koudstaal, P. J.;Hofman, A.;Breteler, M. M.",2003,Dec,10.1007/s00125-003-1235-0,0,
4660,"Vascular risk factors, apolipoprotein E, and hippocampal decline on magnetic resonance imaging over a 10-year follow-up","BACKGROUND: Decline of hippocampal volume on magnetic resonance imaging (MRI) may be considered as a surrogate biomarker of accumulating Alzheimer disease (AD) pathology. Previously, we showed in the prospective population-based Rotterdam Scan Study that a higher rate of decline of hippocampal volume on MRI precedes clinical AD or memory decline. We studied potential risk factors for decline of hippocampal volume. METHODS: At baseline (1995-1996), 518 nondemented elderly subjects were included, and the cohort was re-examined in 1999 and in 2006. At each examination, hippocampal volume was determined using an automated segmentation procedure. In all, 301 persons had at least two three-dimensional MRI scans to assess decline in hippocampal volume. RESULTS: Persons carrying the apolipoprotein E (APOE) varepsilon4 allele had lower hippocampal volumes than persons with the varepsilon3/varepsilon3 genotype, but the rate of decline was not influenced by APOE genotype. In persons who did not use antihypertensive treatment, both a high (>90 mm Hg) and a low (<70 mm Hg) diastolic blood pressure were associated with a faster decline in hippocampal volume. Also, white matter lesions on baseline MRI were associated with a higher rate of decline in hippocampal volume. CONCLUSIONS: In a nondemented elderly population, persons with the APOE varepsilon4 allele have a smaller hippocampal volume but not a higher rate of decline. Rate of decline of hippocampal volume was influenced by white matter lesions and diastolic blood pressure, supporting their hypothesized role in the pathogenesis of AD.","Aged;Aged, 80 and over;Aging/ genetics/ pathology;Apolipoproteins E/ genetics;Cohort Studies;Female;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Risk Factors;Time Factors;Vascular Diseases/epidemiology/pathology","den Heijer, T.;van der Lijn, F.;Ikram, A.;Koudstaal, P. J.;van der Lugt, A.;Krestin, G. P.;Vrooman, H. A.;Hofman, A.;Niessen, W. J.;Breteler, M. M.",2012,Sep,10.1016/j.jalz.2011.07.005,0,
4661,MR spectroscopy of brain white matter in the prediction of dementia,"BACKGROUND: Previous 1H-MR spectroscopy (MRS) studies compared biochemical spectra of persons with dementia with those of healthy control subjects. Given the long prodromal period of Alzheimer disease (AD), the authors sought to investigate whether biochemical changes can be observed also in the preclinical period. METHODS: The authors prospectively followed 509 elderly persons (ages 60 to 90), who were free of clinical dementia at baseline, for on average 5.9 years. At baseline, 1H-MRS of the brain (1.5 T) was performed in a plane above the lateral ventricles that comprised mainly white matter voxels. Standard ratios of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were calculated. Structural MRI was administered to assess white matter lesions and hippocampal atrophy. All persons were followed for incident dementia through repeated neuropsychological testing and linkage with medical records. RESULTS: During follow-up, 37 persons developed dementia, of whom 27 fulfilled criteria for AD. Overall, biochemical ratios on 1H-MRS at baseline were not associated with the risk of incident dementia. However, people with higher Cho/Cr ratios had a higher risk to develop dementia or AD within 4 years (hazard ratio for dementia per SD increase 1.55 [95% CI 1.05 to 2.28]). This association attenuated and became nonsignificant after adjustment for white matter lesions on MRI. CONCLUSION: These data suggest that there are biochemical changes on 1H-MR spectroscopy of brains of persons with presymptomatic dementia.","Aged;Aged, 80 and over;Brain/*anatomy & histology/*pathology;Dementia/*diagnosis;Female;Follow-Up Studies;Humans;Magnetic Resonance Spectroscopy/*methods;Male;Middle Aged;Prospective Studies;Reproducibility of Results;Time Factors","den Heijer, T.;Sijens, P. E.;Prins, N. D.;Hofman, A.;Koudstaal, P. J.;Oudkerk, M.;Breteler, M. M.",2006,Feb 28,10.1212/01.wnl.0000198256.54809.0e,0,
4662,"Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe","BACKGROUND: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. OBJECTIVE: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI-potential in vivo indicators of Alzheimer pathology. METHODS: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. RESULTS: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase -0.10 mL [95% CI -0.19 to -0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. CONCLUSION: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/pathology/physiopathology;Amygdala/pathology;Antihypertensive Agents/therapeutic use;Arteriosclerosis/epidemiology/pathology;Atrophy;*Blood Pressure;Cephalometry;Cohort Studies;Comorbidity;Diastole;Female;Follow-Up Studies;Hippocampus/pathology;Humans;Hypertension/drug therapy/*epidemiology/pathology;Hypotension/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/*pathology;Netherlands;Temporal Lobe/*pathology","den Heijer, T.;Launer, L. J.;Prins, N. D.;van Dijk, E. J.;Vermeer, S. E.;Hofman, A.;Koudstaal, P. J.;Breteler, M. M.",2005,Jan 25,10.1212/01.wnl.0000149641.55751.2e,0,
4663,Serum carotenoids and cerebral white matter lesions: the Rotterdam scan study,"OBJECTIVES: To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Rotterdam Scan Study. PARTICIPANTS: Two hundred and three nondemented older persons, age 60 to 90, from the Rotterdam Scan Study. MEASUREMENTS: Serum levels of carotenoids were determined. WMLs on MRIs were rated separately into periventricular and subcortical WMLs. Odds ratios (ORs) for the presence of severe WMLs (upper decile) were calculated per standard deviation (SD) increase in serum carotenoid level and per SD increase in overall carotenoid serum level. Effect modification by smoking status was studied through stratified analyses. RESULTS: Increasing levels of all the separate carotenoids were associated with less severe periventricular WMLs, which reached statistical significance for the overall carotenoid serum level (OR 0.4 per SD; 95% confidence interval (CI) = 0.2-0.9). We found no association between carotenoid levels and the presence of severe subcortical WMLs (OR 1.2 per SD; 95% CI = 0.7-2.0). The association of carotenoid levels with severe periventricular WMLs was more marked in those who ever smoked (OR 0.1 per SD; 95% CI = 0.0-0.9) than in those who had never smoked (OR 0.9 per SD; 95% CI = 0.4-2.1). CONCLUSIONS: These findings are compatible with the view that high levels of carotenoids may protect against WMLs in the periventricular region, in particular in smokers. Longitudinal studies with repeated measurements of both carotenoids and WMLs are necessary to explore this hypothesis further.","Aged;Aged, 80 and over;Brain Diseases/ blood/classification/epidemiology/ pathology;Carotenoids/ blood;Cohort Studies;Cross-Sectional Studies;Dementia/ blood/classification/epidemiology/ pathology;Female;Geriatric Assessment;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Netherlands/epidemiology;Odds Ratio;Risk Factors;Severity of Illness Index;Smoking/adverse effects;Surveys and Questionnaires;Urban Health/statistics & numerical data","den Heijer, T.;Launer, L. J.;de Groot, J. C.;de Leeuw, F. E.;Oudkerk, M.;van Gijn, J.;Hofman, A.;Breteler, M. M.",2001,May,,0,
4664,Recent progress in translational research on neurovascular and neurodegenerative disorders,"The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient's outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms.This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations.",Alzheimer's disease;brain;cerebral ischemia;cerebral small vessel disease;dementia;experimental therapy;hemorrhage;in vivo imaging;neuroimmunology;neuroprotection;neurorepair;sex differences;stroke;translational research;vascular cognitive impairment,"Demuth, H. U.;Dijkhuizen, R. M.;Farr, T. D.;Gelderblom, M.;Horsburgh, K.;Iadecola, C.;McLeod, D. D.;Michalski, D.;Murphy, T. H.;Orbe, J.;Otte, W. M.;Petzold, G. C.;Plesnila, N.;Reiser, G.;Reymann, K. G.;Rueger, M. A.;Saur, D.;Savitz, S. I.;Schilling, S.;Spratt, N. J.;Turner, R. J.;Vemuganti, R.;Vivien, D.;Yepes, M.;Zille, M.;Boltze, J.;Isn;contributors, N. meeting",2017,,,0,
4665,Feature Selection Improves the Accuracy of Classifying Alzheimer Disease Using Diffusion Tensor Images,"Diffusion tensor imaging (DTI) has recently been added to several large-scale studies of Alzheimer's disease (AD), such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), to investigate white matter (WM) abnormalities not detectable on standard anatomical MRI. Disease effects can be widespread, and the profile of WM abnormalities across tracts is still not fully understood. Here we analyzed image-wide measures from DTI fractional anisotropy (FA) maps to classify AD patients (n=43), mild cognitive impairment (n=114) and cognitively healthy elderly controls (n=70). We used voxelwise maps of FA along with averages in WM regions of interest (ROI) to drive a Support Vector Machine. We further used the ReliefF algorithm to select the most discriminative WM voxels for classification. This improved accuracy for all classification tasks by up to 15%. We found several clusters formed by the ReliefF algorithm, highlighting specific pathways affected in AD but not always captured when analyzing ROIs.",,"Demirhan, A.;Nir, T. M.;Zavaliangos-Petropulu, A.;Jack, C. R., Jr.;Weiner, M. W.;Bernstein, M. A.;Thompson, P. M.;Jahanshad, N.",2015,Apr,10.1109/isbi.2015.7163832,0,
4666,Clinical report of three patients with hereditary hemochromatosis and movement disorders,"Neurologic manifestations are rarely described in hereditary hemochromatosis (HH). We describe three patients with HH and movement disorders. Patient 1, a 69-year-old man, had a 13-year history of disabling cerebellar syndrome, action tremor and myoclonus, and secondary dementia. Patient 2 was a 40-year-old man with a 9-year history of cerebellar syndrome, head and arm tremor, and cervical dystonia. Patient 3, a 75-year-old woman, had a 5-year history of rapidly disabling parkinsonian syndrome unresponsive to levodopa. The diagnosis of HH was established in the three patients by iron tests, evidence of a C282Y mutation, and, in two patients, by liver biopsy. High-field T2-weighted magnetic resonance imaging showed hyperintense signals in hemispheric white matter in patient 1, cerebellar atrophy in patient 2, and cerebellar and cerebral atrophy in patient 3 and no significant hypointense signals in the three patients. Phlebotomies and symptomatic treatments did not change the course of the disease. Our cases are compared with the five previously reported observations of HH with movement disorders. This rare association is one cause of the chronic acquired non-Wilsonian hepatocerebral degeneration syndromes and represents a separate entity from aceruloplasminemia. The pathophysiologic mechanism of movement disorders in HH is unresolved. No hepatic insufficiency and portosystemic encephalopathy is evidenced in our cases, whereas the putative role of abnormal iron load remains to be ascertained. HH should be investigated more systematically in patients with movement disorders.",,"Demarquay, G.;Setiey, A.;Morel, Y.;Trepo, C.;Chazot, G.;Broussolle, E.",2000,2000,,0,
4667,Reaction Time Is Negatively Associated with Corpus Callosum Area in the Early Stages of CADASIL,"BACKGROUND AND PURPOSE: Reaction time was recently recognized as a marker of subtle cognitive and behavioral alterations in the early clinical stages of CADASIL, a monogenic cerebral small-vessel disease. In unselected patients with CADASIL, brain atrophy and lacunes are the main imaging correlates of disease severity, but MR imaging correlates of reaction time in mildly affected patients are unknown. We hypothesized that reaction time is independently associated with the corpus callosum area in the early clinical stages of CADASIL. MATERIALS AND METHODS: Twenty-six patients with CADASIL without dementia (Mini-Mental State Examination score > 24 and no cognitive symptoms) and without disability (modified Rankin Scale score </= 1) were compared with 29 age- and sex-matched controls. Corpus callosum area was determined on 3D-T1 MR imaging sequences with validated methodology. Between-group comparisons were performed with t tests or chi(2) tests when appropriate. Relationships between reaction time and corpus callosum area were tested using linear regression modeling. RESULTS: Reaction time was significantly related to corpus callosum area in patients (estimate = -7.4 x 10(3), standard error = 3.3 x 10(3), P = .03) even after adjustment for age, sex, level of education, and scores of depression and apathy (estimate = -12.2 x 10(3), standard error = 3.8 x 10(3), P = .005). No significant relationship was observed in controls. CONCLUSIONS: Corpus callosum area, a simple and robust imaging parameter, appears to be an independent correlate of reaction time at the early clinical stages of CADASIL. Further studies will determine whether corpus callosum area can be used as an outcome in future clinical trials in CADASIL or in more prevalent small-vessel diseases.",,"Delorme, S.;De Guio, F.;Reyes, S.;Jabouley, A.;Chabriat, H.;Jouvent, E.",2017,Nov,,0,
4668,The structural correlates of functional deficits in early huntington's disease,"Neuropathological studies in Huntington disease (HD) have demonstrated neuronal loss in the striatum, as well as in other brain regions including the cortex. With diffusion tensor MRI we evaluated the hypothesis that the clinical dysfunction in HD is related to regionally specific lesions of circuit-specific cortico-basal ganglia networks rather than to the striatum only. We included 27 HD and 24 controls from the TRACK-HD Paris cohort. The following assessments were used: self-paced tapping tasks, trail B making test (TMT), University of Pennsylvania smell identification test (UPSIT), and apathy scores from the problem behaviors assessment. Group comparisons of fractional anisotropy and mean diffusivity and correlations were performed using voxel-based analysis. In the cortex, HD patients showed significant correlations between: (i) self paced tapping and mean diffusivity in the parietal lobe at 1.8 Hz and prefrontal areas at 3 Hz, (ii) UPSIT and mean diffusivity in the parietal, and median temporal lobes, the cingulum and the insula, and fractional anisotropy in the insula and the external capsule, (iii) TMT B and mean diffusivity in the white matter of the superior frontal, orbital, temporal, superior parietal and post central areas, and (iv) apathy and fractional anisotropy in the white matter of the rectus gyrus. In the basal ganglia, we found correlations between the self paced tapping, UPSIT, TMT tests, and mean diffusivity in the anterior part of the putamen and the caudate nucleus. In conclusion, disruption of motor, associative and limbic cortico-striatal circuits differentially contribute to the clinical signs of the disease. © 2012 Wiley Periodicals, Inc.",adult;article;basal ganglion;clinical assessment;cognition;controlled study;diffusion tensor imaging;external capsule;female;fractional anisotropy;human;Huntington chorea;image processing;insula;major clinical study;male;neuropsychiatry;nuclear magnetic resonance imaging;parietal lobe;priority journal;temporal lobe;white matter,"Delmaire, C.;Dumas, E. M.;Sharman, M. A.;van den Bogaard, S. J. A.;Valabregue, R.;Jauffret, C.;Justo, D.;Reilmann, R.;Stout, J. C.;Craufurd, D.;Tabrizi, S. J.;Roos, R. A. C.;Durr, A.;Lehéricy, S.",2013,,,0,
4669,Structural Connectivity is Differently Altered in Dementia with Lewy Body and Alzheimer's Disease,"The structural connectivity within cortical areas and between cortical and subcortical structures was investigated in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We hypothesized that white matter (WM) tracts, which are linked to visual, attentional, and mnemonic functions, would be differentially and selectively affected in DLB as compared to AD and age-matched control subjects. Structural tensor imaging and diffusion tensor imaging (DTI) were performed on 14 DLB patients, 14 AD patients, and 15 controls. DTI metrics related to WM damage were assessed within tracts reconstructed by FreeSurfer's TRActs Constrained by UnderLying Anatomy pipeline. Correlation analysis between WM and gray matter (GM) metrics was performed to assess whether the structural connectivity alteration in AD and DLB could be secondary to GM neuronal loss or a consequence of direct WM injury. Anterior thalamic radiation (ATR) and cingulum-cingulate gyrus were altered in DLB, whereas cingulum-angular bundle (CAB) was disrupted in AD. In DLB patients, secondary axonal degeneration within ATR was found in relation to microstructural damage within medio-dorsal thalamus, whereas axonal degeneration within CAB was related to precuneus thinning. WM alteration within the uncinate fasciculus was present in both groups of patients and was related to frontal and to temporal thinning in DLB and AD, respectively. We found structural connectivity alterations within fronto-thalamic and fronto-parietal (precuneus) network in DLB whereas, in contrast, disruption of structural connectivity of mnemonic pathways was present in AD. Furthermore, the high correlation between GM and WM metrics suggests that the structural connectivity alteration in DLB could be linked to GM neuronal loss rather than by direct WM injury. Thus, this finding supports the key role of cortical and subcortical atrophy in DLB.",,"Delli Pizzi, S.;Franciotti, R.;Taylor, J. P.;Esposito, R.;Tartaro, A.;Thomas, A.;Onofrj, M.;Bonanni, L.",2015,,10.3389/fnagi.2015.00208,0,
4670,Carotid Intima-Media Thickness Is Associated With White Matter Hyperintensities: The Northern Manhattan Study,"BACKGROUND AND PURPOSE: Brain white matter hyperintensities (WMH) have been associated with increased risk of stroke, cognitive decline, and dementia. WMH can be a manifestation of small vessel disease, although the total microvascular contribution to multifactorial WMH pathophysiology remains unknown. We hypothesized a possible relationship between carotid intima-media thickness (cIMT), an ultrasound imaging marker of subclinical vascular disease, and brain WMH in a multiethnic, elderly stroke-free community-based cohort. METHODS: We evaluated the relationship between cIMT and WMH in the population-based Northern Manhattan Study, among individuals free of stroke. We used linear regression to examine the association of continuous measures of cIMT with quantitatively derived WMH volume, as a proportion of cranial volume, measured from fluid-attenuaded inversion recovery magnetic resonance imaging while adjusting for sociodemographics, lifestyle, and vascular risk factors. RESULTS: In a cohort of 1229 participants (mean age, 71+/-9 years; 60% women, 15% White; 18% Black; 65% Hispanics), the mean cIMT was 0.71+/-0.08 mm and the median log-transformed WMH volume was 0.36 (interquartile range, 0.21-0.76). In a multivariable model, larger cIMT was significantly associated with greater WMH volume (beta=0.046 per SD cIMT; P=0.04). Age and race/ethnicity were significant modifiers (P for age, 0.02; and P for race/ethnicity, 0.04). cIMT was associated with WMH volume in participants 70 years or older (beta=0.088 per SD cIMT; P=0.01) and among Hispanics (beta=0.084 per SD cIMT; P=0.003). CONCLUSIONS: Larger cIMT was associated with greater burden of cerebral WM lesions independently of demographics and traditional vascular risk factors, particularly among elderly and Hispanic participants, who are at high risk for stroke and cognitive decline.",carotid arteries;carotid intima-media thickness;dementia;risk factors;white matter,"Della-Morte, D.;Dong, C.;Markert, M. S.;Elkind, M. S. V.;Sacco, R. L.;Wright, C. B.;Rundek, T.",2018,Feb,,0,
4671,Tract Based Spatial Statistic Reveals No Differences in White Matter Microstructural Organization between Carriers and Non-Carriers of the APOE varepsilon4 and varepsilon2 Alleles in Young Healthy Adolescents,"The apolipoprotein E (APOE) varepsilon4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE varepsilon4 and varepsilon2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuroimaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1,300 s/mm(2) and isotropic resolution of 2.4x2.4x2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE varepsilon4 and varepsilon2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the APOE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the APOE varepsilon4 and varepsilon2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year-olds and may only develop later in life.",,"Dell'Acqua, F.;Khan, W.;Gottlieb, N.;Giampietro, V.;Ginestet, C.;Bouls, D.;Newhouse, S.;Dobson, R.;Banaschewski, T.;Barker, G. J.;Bokde, A. L.;Buchel, C.;Conrod, P.;Flor, H.;Frouin, V.;Garavan, H.;Gowland, P.;Heinz, A.;Lemaitre, H.;Nees, F.;Paus, T.;Pausova, Z.;Rietschel, M.;Smolka, M. N.;Strohle, A.;Gallinat, J.;Westman, E.;Schumann, G.;Lovestone, S.;Simmons, A.",2015,,10.3233/jad-140519,0,
4672,Regional distribution and clinical correlates of white matter structural damage in Huntington disease: a tract-based spatial statistics study,"BACKGROUND AND PURPOSE: HD entails damage of the WM. Our aim was to explore in vivo the regional volume and microstructure of the brain WM in HD and to correlate such findings with clinical status of the patients. MATERIALS AND METHODS: Fifteen HD gene carriers in different clinical stages of the disease and 15 healthy controls were studied with T1-weighted images for VBM and DTI for TBSS. Maps of FA, MD, and lambda parallel and lambda perpendicular were reconstructed. RESULTS: Compared with controls, in addition to neostriatum and cortical GM volume loss, individuals with HD showed volume loss in the genu of the internal capsule and subcortical frontal WM bilaterally, the right splenium of the corpus callosum, and the left corona radiata. TBSS revealed symmetrically decreased FA in the corpus callosum, fornix, external/extreme capsule, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. Areas of increased MD were more extensive and included arciform fibers of the cerebral hemispheres and cerebral peduncles. Increase of the lambda parallel and a comparatively more pronounced increase of the lambda perpendicular underlay the decreased FA of the WM in HD. Areas of WM atrophy, decreased FA, and increased MD correlated with the severity of the motor and cognitive dysfunction, whereas only the areas with increased MD correlated with disease duration. CONCLUSIONS: Microstructural damage accompanies volume decrease of the WM in HD and is correlated with the clinical deficits and disease duration. MR imaging-based measures could be considered as a biomarker of neurodegeneration in HD gene carriers.","Adult;Aged;Brain/ pathology;Data Interpretation, Statistical;Diffusion Tensor Imaging/ methods;Female;Genetic Predisposition to Disease/genetics;Humans;Huntington Disease/ diagnosis/ genetics;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic","Della Nave, R.;Ginestroni, A.;Tessa, C.;Giannelli, M.;Piacentini, S.;Filippi, M.;Mascalchi, M.",2010,Oct,10.3174/ajnr.A2128,0,
4673,A case report about CADASIL: Mutation in the NOTCH 3 receptor,"CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare autosomal dominant genetic disease characterized with recurrent stroke, migrainous headache, cognitive deficits, and psychiatric symptoms associated with mutations in the NOTCH 3 gene on chromosome 19. Here, we report a case of CADASIL who presented with migrainous headache, behavioral disorder, and familial history of stroke and the diagnosis was established by the findings of head magnetic resonance images revealing characteristic white matter lesions and a mutation in the NOTCH 3 gene.",,"Delibas, S.;Guven, H.;Comoglu, S. S.",2009,December,,0,
4674,Prevalence and associated factors of silent brain infarcts in a Mediterranean cohort of hypertensives,"Silent brain infarcts (SBIs) are detected by neuroimaging in approximately 20% of elderly patients in population-based studies. Limited evidence is available for hypertensives at low cardiovascular risk countries. Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study (ISSYS) is aimed to assess the prevalence and risk factors of SBIs in a hypertensive Mediterranean population. This is a cohort study in randomly selected hypertensives, aged 50 to 70 years old, and free of clinical stroke and dementia. On baseline, all participants underwent a brain magnetic resonance imaging to assess prevalence and location of silent infarcts, and data on vascular risk factors, comorbidities, and the presence of subclinical cardiorenal damage (left ventricular hypertrophy and microalbuminuria) were collected. Multivariate analyses were performed to determine SBIs associated factors. A total of 976 patients (49.4% men, mean age 64 years) were enrolled, and 163 SBIs were detected in 99 participants (prevalence 10.1%; 95% CI, 8.4%-12.2%), most of them (64.4%) located in the basal ganglia and subcortical white matter. After adjustment, besides age and sex, microalbuminuria and increasing total cardiovascular risk (assessed by the Framingham-calibrated for Spanish population risk function) were independently associated with SBIs. Male sex increased the odds of having SBIs in 2.5 as compared with females. Our results highlight the importance of considering both global risk assessment and sex differences in hypertension and may be useful to design future preventive interventions of stroke and dementia.","Aged;Albuminuria/ epidemiology;Brain Infarction/ epidemiology;Cohort Studies;Comorbidity;Cross-Sectional Studies;Female;Humans;Hypertension/complications/ epidemiology;Hypertrophy, Left Ventricular/ epidemiology;Longitudinal Studies;Male;Mediterranean Region/epidemiology;Middle Aged;Multivariate Analysis;Neuroimaging;Prevalence;Risk Factors;Sex Factors;Spain/epidemiology","Delgado, P.;Riba-Llena, I.;Tovar, J. L.;Jarca, C. I.;Mundet, X.;Lopez-Rueda, A.;Orfila, F.;Llussa, J.;Manresa, J. M.;Alvarez-Sabin, J.;Nafria, C.;Fernandez, J. L.;Maisterra, O.;Montaner, J.",2014,Sep,10.1161/hypertensionaha.114.03563,0,
4675,CADASIL: How to avoid the unavoidable?,"All three siblings (one female/two males) of a family presented successively with cerebrovascular events at the ages of 55, 63 and 65. The first one manifested extensive left subcortical haemorrhage and both the second and third patient, showed left lacunar ischemic stroke. Their mother had died from vascular dementia at the age of 60 after several subcortical ischaemic strokes. Their maternal grandfather had died in his fifties from haemorrhagic stroke. All of them showed extensive white matter involvement. The genetic study revealed a mutation in exon 11 of the Notch3 gene in two family members. They were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Although CADASIL is a well-established disease, little is known about this disorder. The fact that all three siblings presented with CADASIL successively may appear disheartening, further studies are needed in order to control the clinical course of this devastating and unavoidable disorder. Copyright 2011 BMJ Publishing Group. All rights reserved.",analgesic agent;adult;aged;article;brain hematoma;brain hemorrhage;brain infarction;brain ischemia;CADASIL;case report;chromosome 19;computer assisted tomography;dyslipidemia;dysphasia;exon;family history;female;gene;gene mutation;genetic screening;hemiparesis;human;leukoencephalopathy;male;menopause;migraine;multiinfarct dementia;neuroimaging;NOTCH3 gene;nuclear magnetic resonance imaging;physiotherapy;priority journal;sibling;smoking;white matter,"Delgado, M. G.;Coto, E.;Tuñon, A.;Sáiz, A.",2011,,,0,
4676,Frequency and determinants of poststroke cognitive impairment at three and twelve months in Chile,"Background: A higher risk of poststroke cognitive impairment (CI) has been reported in Hispanics in a US cohort but has not been systematically studied in Latin America. Objectives: Our purpose was to investigate the frequencies and determinants of poststroke CI in the hispano-mestizo population of Santiago, Chile. Methods: A prospective study of hospitalized patients aged >60 years admitted with an ischemic or hemorrhagic stroke was conducted. The cognitive status was determined at 3 and 12 months after the stroke by informant questionnaires, neuropsychological testing and clinical diagnosis. Cardiovascular risk factors, brain imaging and stroke features were analyzed using regression models to establish determinants for poststroke CI. Results: A total of 164 patients (mean age = 72 ± 7.5 years) were recruited. Out of 122 patients (74%) evaluated at 3 months, 81 (66%) had CI. Out of 101 patients (62%) evaluated at 12 months, 39 (39%) had CI no dementia, and 22 (22%) were demented. The new-onset dementia frequency at 1 year was 16%. Independent determinants for dementia were higher functional impairment at hospital egress (OR = 4.0), left-hemisphere large-vessel infarction (OR = 6.9) and a larger amount of white matter changes (OR = 1.3). Conclusions: In this first study on poststroke CI in Latin America, the frequencies and determinants of poststroke CI were similar to those in other cohorts of different ethnic origin. © 2010 S. Karger AG, Basel.",,"Delgado, C.;Donoso, A.;Orellana, P.;Vásquez, C.;Díaz, V.;Behrens, M. I.",2010,June,,0,
4677,"Cerebral blood flow in progressive aphasia without dementia. Case report, using (133)xenon inhalation, technetium 99m hexamethylpropyleneamine oxime and single photon emission computerized tomography","We report a case of progressive aphasia without clinical signs of intellectual or behavioural impairment, satisfying Mesulam's clinical criteria of primary progressive aphasia, as 4 yrs of extensive psychometric testing and radiological imaging, comprising CT and MRI, failed to detect evidence of relevant involvement outside the left perisylvian regions. Cranial CT was normal but MRI showed multiple bilateral lesions in the deep white matter. Cerebral blood flow (CBF) studies by single photon emission computerized tomography, however, showed an initial frontotemporal focus of hypoperfusion that progressively extended to include most of the ipsilateral hemisphere and the contralateral frontal lobe. This suggests that CBF imaging may yet be the most sensitive technique in revealing subclinical injury in the degenerative brain diseases of focal onset.",,"Delecluse, F.;Andersen, A. R.;Waldemar, G.;Thomsen, A. M.;Kjaer, L.;Lassen, N. A.;Postiglione, A.",1990,1990,,0,
4678,Posterior cingulum white matter disruption and its associations with verbal memory and stroke risk in mild cognitive impairment,"Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk.","Aged;Aged, 80 and over;Analysis of Variance;Anisotropy;Apolipoprotein E4/genetics;Attention/physiology;Corpus Callosum/ pathology;Diffusion Magnetic Resonance Imaging;Female;Gyrus Cinguli/ pathology;Humans;Image Processing, Computer-Assisted;Male;Memory/ physiology;Mild Cognitive Impairment/etiology/genetics/ pathology;Neuropsychological Tests;Risk Factors;Stroke/complications/ pathology;Verbal Learning/ physiology","Delano-Wood, L.;Stricker, N. H.;Sorg, S. F.;Nation, D. A.;Jak, A. J.;Woods, S. P.;Libon, D. J.;Delis, D. C.;Frank, L. R.;Bondi, M. W.",2012,,10.3233/jad-2012-102103,0,
4679,Stroke risk modifies regional white matter differences in mild cognitive impairment,"Forty non-demented older adults who were divided into two groups on the basis of their cognitive status (MCI: n=20; normal control: n=20) underwent diffusion tensor imaging, and estimates of fractional anisotropy (FA) and mean diffusivity (MD) were obtained for the genu and splenium of the corpus callosum. Results demonstrated the following: (1) group comparisons revealed that splenium FA was significantly lower in MCI participants than in NC participants, despite no differences in gross morphometry or hippocampal volumes; (2) in the overall sample, higher stroke risk was associated with lower white matter integrity, particularly in the genu; (3) increased stroke risk was more strongly associated with poorer splenium FA in those with MCI than in normal elderly; (4) splenium FA significantly predicted performance on verbal memory (adjusting for the effects of age, education, and whole brain volume). Findings demonstrate a relationship between increased vascular burden and white matter changes, and they support the possibility that posterior white matter pathology may contribute to the development of MCI-related cognitive changes.","Aged;Aged, 80 and over;Anisotropy;Cognition Disorders/ pathology;Cohort Studies;Corpus Callosum/ pathology;Diffusion Tensor Imaging;Female;Hippocampus/ pathology;Humans;Image Processing, Computer-Assisted/methods;Leukoencephalopathies/ pathology;Male;Memory;Risk Factors;Stroke/ pathology","Delano-Wood, L.;Bondi, M. W.;Jak, A. J.;Horne, N. R.;Schweinsburg, B. C.;Frank, L. R.;Wierenga, C. E.;Delis, D. C.;Theilmann, R. J.;Salmon, D. P.",2010,Oct,10.1016/j.neurobiolaging.2008.09.013,0,
4680,Magnetic resonance imaging and positron emission tomography in the diagnosis of neurodegenerative dementias,"Neuroimaging, both with magnetic resonance imaging (MRI) and positron emission tomography (PET), has gained a pivotal role in the diagnosis of primary neurodegenerative diseases. These two techniques are used as biomarkers of both pathology and progression of Alzheimer’s disease (AD) and to differentiate AD from other neurodegenerative diseases. MRI is able to identify structural changes including patterns of atrophy characterizing neurodegenerative diseases, and to distinguish these from other causes of cognitive impairment, e.g. infarcts, space-occupying lesions and hydrocephalus. PET is widely used to identify regional patterns of glucose utilization, since distinct patterns of distribution of cerebral glucose metabolism are related to different subtypes of neurodegenerative dementia. The use of PET in mild cognitive impairment, though controversial, is deemed helpful for predicting conversion to dementia and the dementia clinical subtype. Recently, new radiopharmaceuticals for the in vivo imaging of amyloid burden have been licensed and more tracers are being developed for the assessment of tauopathies and inflammatory processes, which may underlie the onset of the amyloid cascade. At present, the cerebral amyloid burden, imaged with PET, may help to exclude the presence of AD as well as forecast its possible onset. Finally PET imaging may be particularly useful in ongoing clinical trials for the development of dementia treatments. In the near future, the use of the above methods, in accordance with specific guidelines, along with the use of effective treatments will likely lead to more timely and successful treatment of neurodegenerative dementias.",amyloid;biological marker;Alzheimer disease;article;brain atrophy;cognitive defect;degenerative disease;dementia;diffusion tensor imaging;glucose utilization;human;meta analysis (topic);nuclear magnetic resonance imaging;positron emission tomography;spectroscopy,"Del Sole, A.;Malaspina, S.;Magenta Biasina, A.",2016,,10.11138/FNeur/2016.31.4.205,0,
4681,Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: Correlation with cognitive severity,"Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score > 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS ≤ 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS < 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.",aged;Alzheimer disease;article;clinical article;dementia;human;single photon emission computer tomography,"DeKosky, S. T.;Shih, W. J.;Schmitt, F. A.;Coupal, J.;Kirkpatrick, C.",1990,,,0,
4682,Single photon emission computed tomography in the differential diagnosis of dementia,"To assess the value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia SPECT and conventional computed tomography were performed in 77 patients (50 men, 27 women, mean age 59 [28-90] years) with dementia diagnosed by a battery of psychometric tests. In 13 out of 15 patients with dementia of Alzheimer type SPECT showed a typical Alzheimer pattern (bilateral parietotemporal perfusion defects). Both patients with dementia of Pick type had definite decreases in frontal perfussion. All 21 patients with dementia due to Huntington's chorea showed a typical pattern with absent perfusion of the head of the caudate nucleus, although in three of them conventional computed tomography didn't demonstrate complete atrophy of this structure. Out of 23 patients with multi-infarct dementia there were 17 with focal uptake deficits at various sites, while six displayed an Alzheimer pattern. In Korsakow's syndrome (n = 11), Down's syndrome (n = 1), Fahr's syndrome (n = 2), senile chorea (n = 1) and HIV encephalopathy (n = 1) no typical distribution patterns were noted. Single photon emission computed tomography can make a contribution to the diagnosis and classification of primary degeneration dementias and can be used to differentiate them from other forms of dementia.",adult;aged;Alzheimer disease;computer analysis;computer assisted tomography;dementia;differential diagnosis;female;human;Huntington chorea;major clinical study;male;multiinfarct dementia;Pick presenile dementia;priority journal;single photon emission computer tomography,"Deisenhammer, E.;Reisecker, F.;Leblhuber, F.;Holl, K.;Markut, H.;Trenkler, J.;Schneider, I.",1989,,,0,
4683,Alterations in brain phosphate metabolite concentrations in patients with human immunodeficiency virus infection,"Human immunodeficiency virus (HIV)-infected individuals often demonstrate neuropsychiatric impairment; however, it is unclear how brain metabolism may be altered in such patients. We used in vivo phosphorus 31 magnetic resonance spectroscopy to noninvasively assess brain energy and phospholipid metabolism by measuring brain concentrations of adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi), as well as phospholipid compounds and intracellular pH. In study 1, 17 HIV-seropositive men with varying degrees of neuropsychiatric impairment and six control subjects were studied. Localized spectra were obtained from a heterogeneous 5 x 5 x 5-cm volume of interest (VOI). Patients with HIV infection had a significantly lower ATP/Pi ratio and a trend for a lower PCr/Pi ratio than did the control group. In addition, the ATP/Pi and PCr/Pi ratios were both significantly negatively correlated with overall severity of neuropsychiatric impairment. In study 2, three HIV-seropositive men with neuropsychiatric impairment were compared with 11 HIV-seronegative men. Localized phosphorus 31 magnetic resonance spectra were obtained from two relatively homogeneous VOIs: (1) a predominantly white matter VOI, and (2) a predominantly subcortical gray matter VOI. The three HIV-infected patients demonstrated significantly decreased ATP and PCr concentrations in the white matter VOI. These results suggest that HIV infection of the brain may impair brain cellular oxidative metabolism and that the degree of metabolic compromise may be related to the severity of neuropsychiatric impairment.",AIDS Dementia Complex/metabolism/pathology;Adenosine Triphosphate/metabolism;Adult;Brain/pathology;Female;HIV Infections/complications/*metabolism/pathology;Humans;Hydrogen-Ion Concentration;Intracellular Fluid;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Nervous System Diseases/*etiology/metabolism/pathology;Phosphates/metabolism;Phosphocreatine/metabolism;Phospholipids/metabolism,"Deicken, R. F.;Hubesch, B.;Jensen, P. C.;Sappey-Marinier, D.;Krell, P.;Wisniewski, A.;Vanderburg, D.;Parks, R.;Fein, G.;Weiner, M. W.",1991,Feb,,0,
4684,Spreading brain lesions in a familial Creutzfeldt-Jakob disease with V180I mutation over 4 years,"Background: We report a female patient with familial Creutzfeldt-Jakob disease with V180I mutation (fCJD with V180I), who was serially followed up with magnetic resonance imaging (MRI) and electroencephalogram (EEG) for up to four years.Case presentation: At 6 months after the onset, diffusion-weighted images (DWI) and fluid-attenuated inversion recovery (FLAIR) of brain MRI revealed an increased signal intensity in the bilateral frontal, temporal, and parietal cerebral cortex with left dominancy except for the occipital lobe. However, her follow-up MRI at four years showed the high-signal regions spreading to the occipital cerebral cortex in DWI and FLAIR images, and bilateral frontal cerebral white matter in FLAIR images. EEG showed a progressive and general slow high-voltage rhythm from 7-8 to 3-5 c/s over four years, without evidence of periodic synchronous discharge. These findings correspond to the symptom progression even after akinetic mutism at 18 months.Conclusion: We suggest that serial MRI and EEG examinations are useful for early diagnosis of fCJD with V180I and for monitoring disease progression. © 2012 Deguchi et al.; licensee BioMed Central Ltd.",,"Deguchi, K.;Takamiya, M.;Deguchi, S.;Morimoto, N.;Kurata, T.;Ikeda, Y.;Abe, K.",2012,,,0,
4685,A novel useful tool of computerized touch panel-type screening test for evaluating cognitive function of chronic ischemic stroke patients,"Cognitive and affective impairments are important non-motor features of ischemic stroke (IS) related to white-matter hyperintensity, including periventricular hyperintensity (PVH). To confirm the usefulness of a novel computerized touch panel-type screening test, we investigated cognitive and affective functioning among 142 IS patients and 105 age-and gender-matched normal control subjects. Assessment using the mini-mental state examination, Hasegawa Dementia Scale-Revised, and frontal assessment battery revealed reduced cognitive function in IS patients, with the most severe reduction exhibited by cardiogenic embolism patients, followed by lacunar infarction patients, and atherothrombotic infarction patients. Our novel touch panel screening test revealed a similar pattern of results. In addition, PVH grading, classified using Fazekas' magnetic resonance imaging method, was also correlated with cognitive decline and touch panel screening test performance. In contrast, affective function, assessed with the 15-item Geriatric Depression Scale, vitality index, and apathy scale, was not significantly decreased in IS, and did not correlate with touch panel screening test results or PVH, although the number of microbleeds was correlated with apathy scale results. The present findings revealed that IS and PVH grading were significantly correlated with decline in general cognitive status (mini-mental state examination and Hasegawa Dementia Scale-Revised) and frontal lobe function (frontal assessment battery). Performance on all touch panel screening tests was correlated with IS and PVH grading, but was largely independent of depression or apathy. Touch panel screening tests were easily understood and performed by almost all patients with mild cognitive and motor dysfunction, due to visually clear images and simple methods not involving detailed manual-handling tasks such as writing. Touch panel screening tests may provide a useful tool for the early screening of cognitive function.","Aged;Aged, 80 and over;Brain Ischemia/complications/ psychology;Cognition/ physiology;Cognition Disorders/ diagnosis/etiology/psychology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Stroke/complications/ psychology;Touch","Deguchi, K.;Kono, S.;Deguchi, S.;Morimoto, N.;Kurata, T.;Ikeda, Y.;Abe, K.",2013,Oct,10.1016/j.jstrokecerebrovasdis.2012.11.011,0,
4686,Impact of white matter lesions and cognitive deficits on conversion from mild cognitive impairment to Alzheimer's disease,"Mild cognitive impairment (MCI) may represent a prodromal stage of dementia and confers a particularly high annual risk of 10-15% for conversion to Alzheimer's disease (AD). Recent findings suggest that white matter lesion pathology (WML) can negatively influence conversion from MCI to AD. In this study, we examined the predictive value of neuropsychological test results and WML pathology on conversion of MCI to AD. Retrospective neuropsychological and magnetic resonance imaging data were collected for MCI patients seen at the University Clinic of Innsbruck between 2005 and 2011. WML were visually rated using the Fazekas and Scheltens scales. Of the 60 subjects, 31 converted to AD during a follow-up of 18.3 +/- 7.4 months and 29 remained stable. Orientation, MMSE score, word list learning and recall, visual memory, and naming scores were significantly lower in MCI patients converting to AD than in non-converters. Converters had significantly higher Fazekas scores and more WML in periventricular regions. Periventricular WML were negatively associated with psychomotor speed, and subcortical WML were negatively correlated with visual memory at baseline in all MCI patients. Low scores in orientation and verbal delayed recall were predictors of progression from MCI to AD. Periventricular WML correlate with lower cognitive function in patients with MCI. However, deficits in orientation and verbal memory, but not vascular changes, turned out as predictive for conversion from MCI to AD. Consequently, a higher WML burden may represent a serious risk factor but not an early symptom for the imminent conversion to AD.","Aged;Aged, 80 and over;Alzheimer Disease/ epidemiology/ pathology/psychology;Cognition Disorders/epidemiology/pathology/psychology;Disease Progression;Female;Follow-Up Studies;Humans;Male;Middle Aged;Mild Cognitive Impairment/ epidemiology/ pathology/psychology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Retrospective Studies;Risk Factors","Defrancesco, M.;Marksteiner, J.;Deisenhammer, E.;Kemmler, G.;Djurdjevic, T.;Schocke, M.",2013,,10.3233/jad-122095,0,
4687,Changes in white matter integrity before conversion from mild cognitive impairment to Alzheimer's disease,"BACKGROUND: Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15-20% of conversion to Alzheimer's disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD. OBJECTIVE: In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population. METHOD: Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM. RESULTS: At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results. CONCLUSION: Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.",Aged;Alzheimer Disease/ pathology;Atrophy/pathology;Brain Mapping/methods;Case-Control Studies;Disease Progression;Female;Gray Matter/pathology;Humans;Male;Mild Cognitive Impairment/ pathology;Neuropsychological Tests;Retrospective Studies;White Matter/ pathology,"Defrancesco, M.;Egger, K.;Marksteiner, J.;Esterhammer, R.;Hinterhuber, H.;Deisenhammer, E. A.;Schocke, M.",2014,,10.1371/journal.pone.0106062,0,
4688,"Brain behavior relationships among African Americans, whites, and Hispanics","There is an increasing racial and ethnic diversity within the elderly population of the United States. Although increased diversity offers unique opportunities to study novel influences on aging and dementia, some aspects of racial and ethnic research have been hampered by the lack of culturally and linguistically consistent testing protocols. Structural brain imaging is commonly used to study the biology of normal aging and cognitive impairment and may therefore serve to explore potential biologic differences of cognitive impairment among racially and ethnically diverse individuals. To test this hypothesis, we recruited a cohort of approximately 400 African American, white, and Hispanic subjects with various degrees of cognitive ability. Each subject was carefully evaluated using standardized diagnostic protocols that included clinical review of brain magnetic resonance image (MRI) to arrive at a clinical diagnosis of normal cognition, mild cognitive impairment or dementia. Each MRI was then independently quantified for measures of brain, white matter hyperintensities, and hippocampal volumes by a technician blind to subject age, sex, ethnicity, race, and diagnostic category. The appearance of infarction on MRI was also rated by examining neurologists. Regression analyses were used to assess associations with various MRI measures across clinical diagnostic categories in relation to racial and ethnic differences. Hispanic subjects were, on average, significantly younger and had less years of education than African Americans or whites. Whites with dementia were significantly older than both African American and Hispanic dementia patients. Highly significant differences in MRI measures were associated with clinical diagnoses for the group as a whole after adjusting for the effects of age, sex, education, race, and ethnicity. Subsequent independent analyses by racial and ethnic status revealed consistent relationships between diagnostic category and MRI measures. Clinical diagnoses were associated with consistent differences in brain structure among a group of racially and ethnically diverse individuals. We believe these results help to validate current diagnostic assessment of individuals across a broad range of racial, ethnic, linguistic, and educational backgrounds. Moreover, interesting and potentially biologically relevant differences were found that might stimulate further research related to the understanding of dementia etiology within an increasingly racially and ethnically diverse population.",African Americans/ ethnology;Aged;Brain/ pathology;Cognition Disorders/ diagnosis;European Continental Ancestry Group/ ethnology;Female;Hispanic Americans/ ethnology;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Neuropsychological Tests,"DeCarli, C.;Reed, B. R.;Jagust, W.;Martinez, O.;Ortega, M.;Mungas, D.",2008,Oct-Dec,,0,
4689,"Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia","BACKGROUND: Mild cognitive impairment (MCI) is widely viewed as the transition phase between normal aging and Alzheimer disease (AD). Given that MCI can also result from cerebrovascular disease (CVD), the authors used clinical, MRI, and cognitive measures of AD and CVD to test the hypothesis that CVD increases the likelihood of progression from MCI to dementia within 3 years. OBJECTIVE: To examine the impact of CVD on progression of MCI to dementia. METHODS: Fifty-two consecutive patients with MCI (71% men) including many with symptomatic CVD were longitudinally evaluated for 3.1 +/- 1.3 years. MCI was defined as a Clinical Dementia Rating Scale (CDR) score of 0.5. Dementia was defined as progression to a CDR score of > or =1.0. RESULTS: Forty-four percent of the MCI patients had MRI infarcts, 50% of which were symptomatic. Thirty-three percent of patients progressed to dementia, and 37.8% of these had MRI infarcts. Clinically probable or possible AD was diagnosed in approximately 82% of converters. Of the clinical and MRI measures, only hippocampal volume was associated with increased risk to progression (hazard ratio [HR] = 0.31 [95% CI 0.1 to 0.92], p = 0.03). When neuropsychological measures were included in the analysis, memory (HR = 0.90 [95% CI 0.84 to 0.96], p = 0.002) and executive function (HR = 0.96 [95% CI 0.92 to 1.0], p = 0.045) were associated with increased risk of dementia progression, whereas APOE genotype, cerebrovascular risk factors, clinical stroke, presence or absence of lacunes, and extent of white matter hyperintensities did not predict progression. CONCLUSION: Within a heterogenous group of MCI patients, including many with clinically significant CVD, baseline memory and executive performance significantly predicted likelihood to develop dementia.","Aged;Aged, 80 and over;Aging/psychology;Apolipoproteins E/genetics;Cardiovascular Diseases/epidemiology;Cerebrovascular Disorders/*epidemiology/pathology/psychology;Cognition Disorders/*epidemiology/psychology;Dementia/*epidemiology;Diabetes Mellitus/epidemiology;Disease Progression;Female;Follow-Up Studies;Humans;Hyperlipidemias/epidemiology;Life Tables;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory Disorders/*epidemiology/psychology;Middle Aged;Neuropsychological Tests;Prospective Studies;Risk Factors;Stroke/epidemiology","DeCarli, C.;Mungas, D.;Harvey, D.;Reed, B.;Weiner, M.;Chui, H.;Jagust, W.",2004,Jul 27,,0,
4690,"Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study","OBJECTIVE: To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. DESIGN: Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. RESULTS: Subjects with MCI were older (73.5 +/- 3.0 vs 72.1 +/- 2.8 years), consumed less alcohol (3.7 +/- 5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56% +/- 0.82% vs 0.25% +/- 0.34% of cranial volume), and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR = 1.70, P<.05). CONCLUSIONS: Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important.",Aged;Apolipoproteins E/genetics;Blood Vessels/pathology;Brain/*pathology;Cerebral Infarction/psychology;*Cerebrovascular Circulation;Cognition Disorders/diagnosis/*etiology/*genetics/psychology;Cohort Studies;Diseases in Twins/diagnosis/*etiology/*genetics;Genetic Predisposition to Disease;Genotype;Humans;Hypertension/complications;Longitudinal Studies;*Magnetic Resonance Imaging;Male;Mental Recall;National Institutes of Health (U.S.);Prospective Studies;Risk Factors;United States,"DeCarli, C.;Miller, B. L.;Swan, G. E.;Reed, T.;Wolf, P. A.;Carmelli, D.",2001,Apr,,0,
4691,"Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter","Objectives. To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). Methods. Neuropsychological tests, CT, MRI quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. Results. Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. Conclusions. Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways.",adult;aged;Alzheimer disease;article;association cortex;brain atrophy;brain metabolism;brain size;clinical article;cognition;computer assisted tomography;controlled study;female;frontal cortex;glucose utilization;human;male;memory;multiple regression;neocortex;neuropsychological test;normal human;nuclear magnetic resonance imaging;parietal lobe;positron emission tomography;priority journal;task performance;temporal lobe;white matter,"DeCarli, C.;Grady, C. L.;Clark, C. M.;Katz, D. A.;Brady, D. R.;Murphy, D. G. M.;Haxby, J. V.;Salerno, J. A.;Gillette, J. A.;Gonzalez-Aviles, A.;Rapoport, S. I.",1996,,,0,
4692,"Anatomical mapping of white matter hyperintensities (WMH): Exploring the relationships between periventricular WMH, deep WMH, and total WMH burden","Background and Purpose - MRI segmentation and mapping techniques were used to assess evidence in support of categorical distinctions between periventricular white matter hyperintensities (PVWMH) and deep WMH (DWMH). Qualitative MRI studies generally identify 2 categories of WMH on the basis of anatomical localization. Separate pathophysiologies and behavioral consequences are often attributed to these 2 classes of WMH. However, evidence to support these empirical distinctions has not been rigorously sought. Methods - MRI analysis of 55 subjects included quantification of WMH volume, mapping onto a common anatomical image, and spatial localization of each WMH voxel. WMH locations were then divided into PVWMH and DWMH on the basis of distance from the lateral ventricles and correlations, with total WMH volume determined. Periventricular distance histograms of WMH voxels were also calculated. Results - PVWMH and DWMH were highly correlated with total WMH (R(2)>0.95) and with each other (R(2)>0.87). Mapping of all WMH revealed smooth expansion from around central cerebrospinal fluid spaces into more distal cerebral white matter with increasing WMH volume. Conclusion - PVWMH, DWMH, and total WMH are highly correlated with each other. Moreover, spatial analysis failed to identify distinct subpopulations for PVWMH and DWMH. These results suggest that categorical distinctions between PVWMH and DWMH may be arbitrary, and conclusions regarding individual relationships between causal factors or behavior for PVWMH and DWMH may more accurately reflect total WMH volume relationships.",,"DeCarli, C.;Fletcher, E.;Ramey, V.;Harvey, D.;Jagust, W. J.",2005,January,,0,
4693,The prevalence of computed tomographic abnormalities of the cerebrum in 100 consecutive children symptomatic with the human immune deficiency virus,"Qualitative analysis of 100 consecutive computed tomographic (CT) studies of the brain in children with symptomatic but untreated acquired immunodeficiency syndrome was performed. After excluding children with associated medical illnesses that might confound the diagnosis of encephalopathy or alter brain structure, an abnormality of at least one of the measures of ventricular size, cortical atrophy, white matter attenuation (leukoaraiosis), or cerebral calcification was found in 86% of the patients studied. Ventricular enlargement was the most common abnormality, followed by cortical atrophy, leukoaraiosis, and cerebral calcification. Cerebellar atrophy was an unexpected but relatively common finding in 12% of the children. Sixty-five percent of the children were encephalopathic at the time of evaluation. All 16 children with cerebral calcification were encephalopathic and had acquired human immunodeficiency virus (HIV) through vertical transmission. Encephalopathic children were significantly younger and had significantly greater abnormality ratings on each CT measure when compared with the nonencephalopathic children. Discriminant analysis using age and the qualitative CT measures was applied as a method to identify the presence of encephalopathy. CT measures proved to have a specificity and a sensitivity of only 76%. We conclude that abnormalities of cerebral structure are seen in a high percentage of children symptomatic with HIV. Although most of the children are encephalopathic, CT abnormalities are seen in children without encephalopathy, suggesting presymptomatic brain disease. The presence of cerebral calcification on CT suggests in utero infection with HIV and the presence of encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)","AIDS Dementia Complex/pathology/*radiography;Atrophy;Brain/pathology/*radiography;Brain Diseases/etiology/pathology/radiography;Calcinosis/etiology/pathology/radiography;Child;Child, Preschool;Female;Humans;Infant;Male;*Tomography, X-Ray Computed","DeCarli, C.;Civitello, L. A.;Brouwers, P.;Pizzo, P. A.",1993,Aug,10.1002/ana.410340216,0,
4694,Clinically asymptomatic vascular brain injury: A potent cause of cognitive impairment among older individuals,"Cerebrovascular risk factors and stroke are highly prevalent with advancing age, and stroke may be more common than Alzheimer's disease, particularly among older men. While stroke mortality continues to decline, the prevalence of individuals with various vascular risk factors continues to rise and many are undiagnosed or undertreated. Asymptomatic cerebrovascular brain injury that includes asymptomatic brain infarction and white matter hyperintensities as well as accelerated brain atrophy is even more frequent than clinical stroke. Moreover, the impact of cerebrovascular risk factors on brain injury appears to begin in middle life and additively increases the likelihood of later life dementia. This review focuses on the use of neuroimaging and genetics to understand the impact of asymptomatic vascular risk factors on the trajectories of cognitive aging as well as incident cognitive impairment, stroke, and mortality. Results of this review emphasize the need for early detection and treatment of vascular risk factors to improve the cognitive health of our rapidly aging population. © 2013 The authors and IOS Press. All rights reserved.",aging;anatomical variation;article;asymptomatic disease;brain size;cerebrovascular accident;cerebrovascular disease;cognitive defect;computer assisted tomography;disease association;early diagnosis;genetic trait;genotype environment interaction;human;illness trajectory;leukoaraiosis;mental health;mortality;neuroanatomy;neuroimaging;risk assessment;risk factor;systolic blood pressure;white matter hyperintensity;white matter lesion,"DeCarli, C.",2012,,,0,
4695,Association of parental dementia with cognitive and brain MRI measures in middle-aged adults,"OBJECTIVES: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort. METHODS: A total of 717 Framingham offspring (mean age: 59 +/- 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally. RESULTS: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE epsilon4 status (p < 0.002). In APOE epsilon4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta = -1.81 +/- 0.53, p < 0.001) and visuospatial memory (beta = -1.73 +/- 0.47, p < 0.001). These associations were stronger for parental AD (beta = -1.97 +/- 0.52, p < 0.001, beta = -1.95 +/- 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE epsilon4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE epsilon4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04). CONCLUSIONS: Among middle-aged carriers of the APOE epsilon4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.",Aged;Alleles;Alzheimer Disease/genetics;Apolipoprotein E4/*genetics;Atrophy;Brain/*pathology;*Cognition;Cohort Studies;Dementia/*genetics/psychology;Female;Heterozygote;Humans;Language;*Magnetic Resonance Imaging;Male;Memory Disorders/*genetics;Middle Aged;Parents/*psychology;Prospective Studies;Space Perception;Visual Perception,"Debette, S.;Wolf, P. A.;Beiser, A.;Au, R.;Himali, J. J.;Pikula, A.;Auerbach, S.;Decarli, C.;Seshadri, S.",2009,Dec 15,10.1212/WNL.0b013e3181c67833,0,
4696,Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline,"OBJECTIVE: Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline. METHODS: A total of 1,352 participants without dementia from the prospective Framingham Offspring Cohort Study were examined. Multivariable linear and logistic regressions were implemented to study the association of midlife vascular risk factor exposure with longitudinal change in white matter hyperintensity volume (WMHV), total brain volume (TBV), temporal horn volume, logical memory delayed recall, visual reproductions delayed-recall (VR-d), and Trail-Making Test B-A (TrB-A) performance a decade later. RESULTS: Hypertension in midlife was associated with accelerated WMHV progression (p < 0.001) and worsening executive function (TrB-A score; p = 0.012). Midlife diabetes and smoking were associated with a more rapid increase in temporal horn volume, a surrogate marker of accelerated hippocampal atrophy (p = 0.017 and p = 0.008, respectively). Midlife smoking also predicted a more marked decrease in total brain volume (p = 0.025) and increased risk of extensive change in WMHV (odds ratio = 1.58 [95%confidence interval 1.07-2.33], p = 0.021). Obesity in midlife was associated with an increased risk of being in the top quartile of change in executive function (1.39 [1.02-1.88], p = 0.035) and increasing waist-to-hip ratio was associated with marked decline in TBV (10.81 [1.44-81.01], p = 0.021). Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function. CONCLUSIONS: Midlife hypertension, diabetes, smoking, and obesity were associated with an increased rate of progression of vascular brain injury, global and hippocampal atrophy, and decline in executive function a decade later.",Aged;*Aging;Apolipoproteins E/genetics;Brain/*pathology;Cerebrovascular Circulation/*physiology;Cognition Disorders/*pathology;Cohort Studies;Female;Humans;Hypertension/physiopathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Regression Analysis;Risk Factors;Statistics as Topic,"Debette, S.;Seshadri, S.;Beiser, A.;Au, R.;Himali, J. J.;Palumbo, C.;Wolf, P. A.;DeCarli, C.",2011,Aug 2,10.1212/WNL.0b013e318227b227,0,
4697,The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis (Provisional abstract),,"Cerebrovascular Disorders [pathology];Cognition Disorders [pathology] [prevention & control];Dementia, Vascular [pathology] [prevention & control];Disease Progression;Longitudinal Studies;Magnetic Resonance Angiography;Microcirculation;Prognosis;Risk Factors;Stroke [pathology] [prevention & control];Humans[checkword]","Debette, S.;Markus, H. S.",2010,,,0,
4698,Subcortical hyperintensities are associated with cognitive decline in patients with mild cognitive impairment,"BACKGROUND AND PURPOSE: It has been suggested that subcortical lesions may influence cognitive performances at early stages of cognitive impairment but not in late stages of dementia. We aimed to test whether cognitive decline is associated with subcortical hyperintensities in patients with mild cognitive impairment (MCI). METHODS: We included 170 consecutive MCI patients (mean follow-up, 3.8+/-1.6 years). We assessed subcortical hyperintensities on a baseline magnetic resonance imaging scan with a semiquantitative rating scale. The mean annual cognitive decline was calculated with the Mini-Mental State Examination and the Dementia Rating Scale at baseline and the end of follow-up. RESULTS: Compared with patients whose cognitive performances remained stable or improved during follow-up, patients whose cognitive performances declined often had a larger amount (greater than the median of the distribution) of periventricular (PVH) (P=0.0005) and white-matter (P=0.02) hyperintensities. The rate of cognitive decline was higher with increasing PVH: mean change in the Mini-Mental State Examination score=0.16 vs -0.66 points/year in patients with PVH in the first versus third tertile (P=0.0002). The rate of decline in executive functioning was also higher with increasing PVH: mean change in the Dementia Rating Scale initiation subscore=-0.05 vs -1.42 points/year in patients with PVH in the first versus third tertile (P=0.04). These associations were independent of vascular risk factors, temporal lobe atrophy, and MCI subtype and were stronger in patients with baseline executive dysfunction. CONCLUSIONS: White-matter hyperintensities and especially PVH were significantly associated with cognitive decline in MCI patients. This result was independent of the MCI subtype but stronger in cases of executive dysfunction at baseline.","Aged;Aged, 80 and over;Brain Infarction/diagnosis/epidemiology/physiopathology;Cerebral Arteries/pathology/physiopathology;Cerebrum/blood supply/ pathology/physiopathology;Cognition Disorders/ epidemiology/physiopathology/psychology;Comorbidity;Dementia, Vascular/ diagnosis/ epidemiology/physiopathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Microcirculation/pathology/physiopathology;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Predictive Value of Tests;Prospective Studies;Risk Factors;Temporal Lobe/pathology/physiopathology","Debette, S.;Bombois, S.;Bruandet, A.;Delbeuck, X.;Lepoittevin, S.;Delmaire, C.;Leys, D.;Pasquier, F.",2007,Nov,10.1161/strokeaha.107.488403,0,
4699,Visceral fat is associated with lower brain volume in healthy middle-aged adults,"OBJECTIVE: Midlife obesity has been associated with an increased risk of dementia. The underlying mechanisms are poorly understood. Our aim was to examine the cross-sectional association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic resonance imaging (MRI) markers of brain aging in middle-aged community adults. METHODS: Participants from the Framingham Offspring cohort were eligible if in addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone a volumetric brain MRI scan with measurements of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts (BI). All analyses were adjusted for age, sex, and time interval between abdominal CT and brain MRI. RESULTS: In a sample of 733 community participants (mean age, 60 years; 53% women), we observed an inverse association of BMI (estimate by standard deviation unit +/- standard error = -0.27 +/- 0.12; p = 0.02), WC (-0.30 +/- 0.12; p = 0.01), WHR (-0.37 +/- 0.12; p = 0.02), SAT (-0.23 +/- 0.11; p = 0.04), and VAT (-0.36 +/- 0.12; p = 0.002) with TCBV, independent of vascular risk factors. The association between VAT and TCBV was the strongest and most robust, and was also independent of BMI (-0.35 +/- 0.15; p = 0.02) and insulin resistance (-0.32 +/- 0.13; p = 0.01). When adjusting for C-reactive protein levels, the associations were attenuated (-0.17 +/- 0.13; p = 0.17 for VAT). No consistently significant association was observed between the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI. INTERPRETATION: In middle-aged community participants, we observed a significant inverse association of anthropometric and CT-based measurements of abdominal, especially visceral, fat with total brain volume.","Age Factors;Aged;Body Mass Index;Brain/ physiology/radiography;Cohort Studies;Comorbidity;Female;Humans;Intra-Abdominal Fat/ physiology;Male;Middle Aged;Subcutaneous Fat/physiology/radiography;Tomography, X-Ray Computed","Debette, S.;Beiser, A.;Hoffmann, U.;Decarli, C.;O'Donnell, C. J.;Massaro, J. M.;Au, R.;Himali, J. J.;Wolf, P. A.;Fox, C. S.;Seshadri, S.",2010,Aug,10.1002/ana.22062,0,
4700,"Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study","BACKGROUND AND PURPOSE: White matter hyperintensities and MRI-defined brain infarcts (BIs) have individually been related to stroke, dementia, and mortality in population-based studies, mainly in older people. Their significance in middle-aged community-dwelling persons and the relative importance of these associations remain unclear. We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort. METHODS: A total of 2229 Framingham Offspring Study participants aged 62+/-9 years underwent volumetric brain MRI and neuropsychological testing (1999 to 2005). Incident stroke, dementia, and mortality were prospectively ascertained and for 1694 participants in whom a second neuropsychological assessment was performed (2005 to 2007), incident mild cognitive impairment was evaluated. All outcomes were related to white matter hyperintensities volume (WMHV), age-specific extensive WMHV and BI adjusting for age and gender. RESULTS: Extensive WMHV and BI were associated with an increased risk of stroke (hazard ratio [HR]=2.28, 95% CI: 1.02 to 5.13; HR=2.84, 95% CI: 1.32 to 6.10). WMHV, extensive WMHV, and BI were associated with an increased risk of dementia (HR=2.22, 95% CI: 1.32 to 3.72; HR=3.97, 95% CI: 1.10 to 14.30; HR=6.12, 95% CI: 1.82 to 20.54) independently of vascular risk factors and interim stroke. WMHV and extensive WMHV were associated with incident amnestic mild cognitive impairment in participants aged > or = 60 years only (OR=2.47, 95% CI: 1.31 to 4.66 and OR=1.49, 95% CI: 1.14 to 1.97). WMHV and extensive WMHV were associated with an increased risk of death (HR=1.38, 95% CI: 1.13 to 1.69; HR=2.27, 95% CI: 1.41 to 3.65) independent of vascular risk factors and of interim stroke and dementia. CONCLUSIONS: In a large community-based sample of middle-aged adults, BI predicted an increased risk of stroke and dementia independent of vascular risk factors. White matter hyperintensities portended an increased risk of stroke, amnestic mild cognitive impairment, dementia, and death independent of vascular risk factors and interim vascular events.","Adult;Aged;Aged, 80 and over;*Cerebrovascular Trauma/complications/mortality/pathology;*Cognition Disorders/etiology/pathology/physiopathology;Dementia;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Prospective Studies;Risk Factors;*Stroke/etiology/pathology/physiopathology","Debette, S.;Beiser, A.;DeCarli, C.;Au, R.;Himali, J. J.;Kelly-Hayes, M.;Romero, J. R.;Kase, C. S.;Wolf, P. A.;Seshadri, S.",2010,Apr,10.1161/strokeaha.109.570044,1,
4701,Radiation-induced dementia in patients cured of brain metastases,"When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.","Aged;Ataxia/etiology;Brain/pathology/radiation effects;Brain Neoplasms/complications/radiography/*radiotherapy;Cerebrospinal Fluid Shunts;Dementia/*etiology;Female;Gait/radiation effects;Humans;Hydrocephalus/complications/surgery;Magnetic Resonance Imaging;Male;Memory Disorders/etiology;Middle Aged;*Radiation Injuries;Tomography, X-Ray Computed","DeAngelis, L. M.;Delattre, J. Y.;Posner, J. B.",1989,Jun,,0,
4702,Brain differences in infants at differential genetic risk for late-onset alzheimer disease: A cross-sectional imaging study,"Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades. Early detection of these alterations holds inherent value for the development and evaluation of preventive treatment therapies. OBJECTIVE: To compare magnetic resonance imaging measurements of white matter myelin water fraction (MWF) and gray matter volume (GMV) in healthy infant carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele, the major susceptibility gene for late-onset AD. DESIGN, SETTING, AND PARTICIPANTS: Quiet magnetic resonance imaging was performed at an academic research imaging center on 162 healthy, typically developing 2- to 25-month-old infants with no family history of Alzheimer disease or other neurological or psychiatric disorders. Cross-sectional measurements were compared in the APOE ε4 carrier and noncarrier groups. White matter MWF was compared in one hundred sixty-two 2- to 25-month-old sleeping infants (60 ε4 carriers and 102 noncarriers). Gray matter volume was compared in a subset of fifty-nine 6- to 25-month-old infants (23 ε4 carriers and 36 noncarriers), who remained asleep during the scanning session. The carrier and noncarrier groups were matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. MAINOUTCOMES AND MEASURES: Automated algorithms compared regional white matter MWF and GMV in the carrier and noncarrier groups and characterized their associations with age. RESULTS: Infant ε4 carriers had lower MWF and GMV measurements than noncarriers in precuneus, posterior/middle cingulate, lateral temporal, and medial occipitotemporal regions, areas preferentially affected by AD, and greater MWF and GMV measurements in extensive frontal regions and measurements were also significant in the subset of 2- to 6-month-old infants (MWF differences, P < .05, after correction for multiple comparisons; GMV differences, P < .001, uncorrected for multiple comparisons). Infant ε4 carriers also exhibited an attenuated relationship between MWF and age in posterior white matter regions. CONCLUSIONS AND RELEVANCE: While our findings should be considered preliminary, this study demonstrates some of the earliest brain changes associated with the genetic predisposition to AD. It raises new questions about the role of APOE in normal human brain development, the extent to which these processes are related to subsequent AD pathology, and whether they could be targeted by AD prevention therapies. Copyright 2014 American Medical Association. All rights reserved.",,"Dean, I. D. C.;Jerskey, B. A.;Chen, K.;Protas, H.;Thiyyagura, P.;Roontiva, A.;O'Muircheartaigh, J.;Dirks, H.;Waskiewicz, N.;Lehman, K.;Siniard, A. L.;Turk, M. N.;Hua, X.;Madsen, S. K.;Thompson, P. M.;Fleisher, A. S.;Huentelman, M. J.;Deoni, S. C. L.;Reiman, E. M.",2014,January,,0,
4703,Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease,"Importance: The accumulation of aggregated beta-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. Objective: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. Design, Setting, and Participants: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including beta-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. Main Outcomes and Measures: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. Results: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/beta-amyloid 42, suggesting that phosphorylated tau 181/beta-amyloid 42 levels modulate age-related changes in myelin water fraction. Conclusions and Relevance: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease's course and lead to new markers of efficacy for prevention and treatment trials.",,"Dean, D. C., 3rd;Hurley, S. A.;Kecskemeti, S. R.;O'Grady, J. P.;Canda, C.;Davenport-Sis, N. J.;Carlsson, C. M.;Zetterberg, H.;Blennow, K.;Asthana, S.;Sager, M. A.;Johnson, S. C.;Alexander, A. L.;Bendlin, B. B.",2017,Jan 01,,0,
4704,Neuroanatomical correlates of prion disease progression - a 3T longitudinal voxel-based morphometry study,"Purpose MRI has become an essential tool for prion disease diagnosis. However there exist only a few serial MRI studies of prion patients, and these mostly used whole brain summary measures or region of interest based approaches. We present here the first longitudinal voxel-based morphometry (VBM) study in prion disease. The aim of this study was to systematically characterise progressive atrophy in patients with prion disease and identify whether atrophy in specific brain structures correlates with clinical assessment. Methods Twenty-four prion disease patients with early stage disease (3 sporadic, 2 iatrogenic, 1 variant and 18 inherited CJD) and 25 controls were examined at 3T with a T1-weighted 3D MPRAGE sequence at multiple time-points (2–6 examinations per subject, interval range 0.1–3.2 years). Longitudinal VBM provided intra-subject and inter-subject image alignment, allowing voxel-wise comparison of progressive structural change. Clinical disease progression was assessed using the MRC Prion Disease Rating Scale. Firstly, in patients, we determined the brain regions where grey and white matter volume change between baseline and final examination correlated with the corresponding change in MRC Scale score. Secondly, in the 21/24 patients with interscan interval longer than 3 months, we identified regions where annualised rates of regional volume change in patients were different from rates in age-matched controls. Given the heterogeneity of the cohort, the regions identified reflect the common features of the different prion sub-types studied. Results In the patients there were multiple regions where volume loss significantly correlated with decreased MRC scale, partially overlapping with anatomical regions where yearly rates of volume loss were significantly greater than controls. The key anatomical areas involved included: the basal ganglia and thalamus, pons and medulla, the hippocampal formation and the superior parietal lobules. There were no areas demonstrating volume loss significantly higher in controls than patients or negative correlation between volume and MRC Scale score. Conclusions Using 3T MRI and longitudinal VBM we have identified key anatomical regions of progressive volume loss which correlate with an established clinical disease severity index and are relevant to clinical deterioration. Localisation of the regions of progressive brain atrophy correlating most strongly with clinical decline may help to provide more targeted imaging endpoints for future clinical trials.",adult;aged;article;basal ganglion;brain atrophy;brain region;brain size;clinical article;clinical assessment;controlled study;correlation analysis;disease course;familial Creutzfeldt Jakob disease;female;hippocampus;human;iatrogenic Creutzfeldt Jakob disease;longitudinal study;male;medulla oblongata;MRC Prion Disease Rating Scale;neuroanatomy;pons;prion disease;priority journal;rating scale;sporadic Creutzfeldt Jakob disease;superior parietal lobule;thalamus;variant Creutzfeldt Jakob disease;voxel based morphometry;white matter;TIM Trio,"De Vita, E.;Ridgway, G. R.;White, M. J.;Porter, M. C.;Caine, D.;Rudge, P.;Collinge, J.;Yousry, T. A.;Jager, H. R.;Mead, S.;Thornton, J. S.;Hyare, H.",2017,,10.1016/j.nicl.2016.10.021,0,
4705,Lymphomatosis cerebri as the cause of leukoencephalopathy,"Introduction. Lymphomatosis cerebri (LC) is an infrequent type of primary lymphoma of the central nervous system that is characterised by diffuse, infiltrating involvement of the white matter of the brain without the formation of a mass. Aim. To report the case of a patient with LC in order to draw attention to this disease, which is rarely diagnosed, and to its initial presentation in magnetic resonance imaging (MRI) as leukoencephalopathy. Case report. Our patient was a 56-year-old female who had clinical signs and symptoms of sub-acute dementia. Computerised axial tomography and MRI of the head revealed extensive, diffuse and bilateral involvement of the white matter, basal nuclei, mesencephalon and pons, with no mass effect or contrast enhancement. A stereotactic biopsy of the white matter (which was not conclusive) showed a perivascular mixed mononuclear-cell inflammatory infiltrate of B and T cells. No cytologic atypia was observed. Treatment was established with corticoids, which produced a clinical and radiological improvement in the first two months. During the next month the patient underwent rapid clinical deterioration with sleepiness and a worsening of the ability to walk. In an MRI scan the lesion had a more heterogeneous appearance with mass effect on adjacent structures and patchy contrast enhancement. A wedge biopsy of brain tissue led to a diagnosis of high-grade B-cell lymphoma. Conclusions. The imaging and histological appearance of LC may not be the one typically found in primary lymphomas of the central nervous system, and its clinical presentation may be similar to that of other diffuse processes involving compromise of the white matter (cerebral gliomatosis, inflammatory diseases of the white matter, such as Behçet's disease, Sjögren's disease or systemic lupus erythematosus). © 2008, Revista de Neurología.",,"De Toledo Heras, M.;López-Valdés, E.;Ferreiro, M.;Cervera, J. L.;Ramos, A.;Cabello, A.;Hernández-Laín, A.;Montes-Montes, S.;Lagares, A.;Álvarez-Linera Prado, J.",2008,June,,0,
4706,Magnetic resonance imaging of cardiovascular function and the brain: Is dementia a cardiovascular-driven disease?,"The proximal aorta acts as a coupling device between heart and brain perfusion, modulating the amount of pressure and flow pulsatility transmitted into the cerebral microcirculation. Stiffening of the proximal aorta is strongly associated with age and hypertension. The detrimental effects of aortic stiffening may result in brain damage as well as heart failure. The resulting cerebral small vessel disease and heart failure may contribute to early cognitive decline and (vascular) dementia. This pathophysiological sequence of events underscores the role of cardiovascular disease as a contributory mechanism in causing cognitive decline and dementia and potentially may provide a starting point for prevention and treatment. Magnetic resonance imaging is well suited to assess the function of the proximal aorta and the left ventricle (eg, aortic arch pulse wave velocity and distensibility) as well as the various early and late manifestations of cerebral small vessel disease (eg, microbleeds and white matter hyperintensities in strategically important regions of the brain). Specialized magnetic resonance imaging techniques are explored for diagnosing preclinical changes in white matter integrity or brain microvascular pulsatility.",aging;aorta;aortic arch;aortic root;arterial stiffness;artery compliance;article;ascending aorta;brain blood flow;brain damage;brain function;brain microcirculation;brain perfusion;cardiovascular disease;cardiovascular function;cardiovascular risk;cerebrovascular disease;cognitive defect;dementia;heart cycle;heart failure;heart function;heart left ventricle;human;mental deterioration;neuroimaging;nuclear magnetic resonance imaging;pathophysiology;priority journal;pulse pressure;pulse wave;systolic blood pressure;white matter,"De Roos, A.;Van Der Grond, J.;Mitchell, G.;Westenberg, J.",2017,,10.1161/circulationaha.116.021978,0,
4707,The significance of cortical cerebellar microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases. A post-mortem 7.0-tesla magnetic resonance study with neuropathological correlates,"BACKGROUND: As cortical microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases have been studied predominantly at the level of the cerebral hemispheres and linked to the presence of cerebral amyloid angiopathy (CAA), we aimed at determining with 7.0-tesla magnetic resonance imaging (MRI) whether the causes and the frequency of cortical cerebellar microbleeds (CCeMBs) and microinfarcts (CCeMIs) are the same. MATERIALS AND METHODS: Hundred and four postmortem brains, composed of 29 with pure Alzheimer's disease (AD), 9 with AD associated to CAA, 10 with frontotemporal lobar degeneration, 9 with amyotrophic lateral sclerosis, 10 with Lewy body disease, 12 with progressive supranuclear palsy, 9 with vascular dementia (VaD), and 16 controls, were examined. On a horizontal section of a cerebellar hemisphere examined with 7.0-tesla MRI, the number CCeMBs and CCeMIs were compared between the different disease groups and the control group. The MRI findings were also compared with the corresponding mean values observed on histological examination of a separate standard horizontal section of a cerebellar hemisphere, used for diagnostic purpose. RESULTS: CCeMBs and CCeMIs were only significantly increased in the VaD group. When comparing the diseased patients with and without CAA mutually and with those with arterial hypertension and severe atherosclerotic cerebrovascular disease, only in the latter an increase of CCeMBs and CCeMIs was observed. There was an excellent correlation between the MRI and the neuropathological findings. CONCLUSIONS: CCeMBs and CCeMIs are mainly due to atherosclerotic cerebrovascular disease and not due to CAA. Their increased presence cannot be included to the Boston diagnostic criteria for CAA.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Amyotrophic Lateral Sclerosis/complications/pathology;Autopsy;Brain Infarction/complications/ pathology;Case-Control Studies;Cerebellar Cortex/ pathology;Cerebellar Diseases/ pathology;Cerebral Amyloid Angiopathy/complications/pathology;Cerebrovascular Disorders/complications/pathology;Dementia, Vascular/complications/pathology;Female;Frontotemporal Lobar Degeneration/complications/pathology;Humans;Intracranial Hemorrhages/complications/ pathology;Lewy Body Disease/complications/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Neurodegenerative Diseases/complications/ pathology;Supranuclear Palsy, Progressive/complications/pathology","De Reuck, J. L.;Deramecourt, V.;Auger, F.;Durieux, N.;Cordonnier, C.;Devos, D.;Defebvre, L.;Moreau, C.;Capparos-Lefebvre, D.;Pasquier, F.;Leys, D.;Maurage, C. A.;Bordet, R.",2015,,10.1159/000371488,0,
4708,Microbleeds in postmortem brains of patients with Alzheimer disease: a T2*-weighted gradient-echo 7.0 T magnetic resonance imaging study,"This study aims to determine the distribution and to quantify microbleeds (MBs) in postmortem brains of patients with Alzheimer disease (AD) on T2*-weighted gradient-echo 7.0 T magnetic resonance imaging. Twenty-eight AD brains were compared with 5 controls. The AD brains were subdivided further: 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central, and the occipital level of a cerebral hemisphere. MBs prevailed in the central sections (P=0.005) of AD brains without CAA, whereas in AD-CAA brains, they were more frequent in all coronal sections (P</=0.002). They prevailed in the deep cortical layers of the AD brains and of the controls (P</=0.03). They were significantly increased in all cortical layers of the AD-CAA brains (P</=0.04), compared with the controls. MBs prevalence in brains of AD patients had a different topographic distribution according to the absence or presence of severe CAA.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology;Autopsy;Cerebral Amyloid Angiopathy/complications/pathology;Cerebral Hemorrhage/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male","De Reuck, J. L.;Cordonnier, C.;Deramecourt, V.;Auger, F.;Durieux, N.;Bordet, R.;Maurage, C. A.;Leys, D.;Pasquier, F.",2013,Apr-Jun,10.1097/WAD.0b013e318256ecd8,0,
4709,Detection of Cortical Microbleeds in Postmortem Brains of Patients with Lewy Body Dementia: A 7.0-Tesla Magnetic Resonance Imaging Study with Neuropathological Correlates,"Background: It is unclear whether associated cerebrovascular pathology contributes to the clinical spectrum of Lewy body dementia (LBD). Summary: The present postmortem 7.0-tesla MRI study investigates the anatomical distribution of cortical microbleeds (CoMBs) in LBD brains with and without associated Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). CoMBs predominated in the frontal section of the LBD brains and were associated to severe white matter lesions. No differences were observed when LBD brains with and without AD and CAA were compared. Key Messages: In LBD, there is a specific distribution of CoMBs that is different from that in other neurodegenerative diseases. The increase of frontal CoMBs is not due to the frequently associated AD and CAA features but due to the LBD itself.",Alzheimer disease;brain;cerebrovascular disease;degenerative disease;diffuse Lewy body disease;human;nuclear magnetic resonance imaging;patient;vascular amyloidosis;white matter;white matter lesion,"De Reuck, J. L.;Auger, F.;Durieux, N.;Cordonnier, C.;Deramecourt, V.;Lebert, F.;Leys, D.;Pasquier, F.;Maurage, C. A.;Bordet, R.",2015,,10.1159/000441057,0,4710
4710,Detection of Cortical Microbleeds in Postmortem Brains of Patients with Lewy Body Dementia: A 7.0-Tesla Magnetic Resonance Imaging Study with Neuropathological Correlates,"BACKGROUND: It is unclear whether associated cerebrovascular pathology contributes to the clinical spectrum of Lewy body dementia (LBD). SUMMARY: The present postmortem 7.0-tesla MRI study investigates the anatomical distribution of cortical microbleeds (CoMBs) in LBD brains with and without associated Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). CoMBs predominated in the frontal section of the LBD brains and were associated to severe white matter lesions. No differences were observed when LBD brains with and without AD and CAA were compared. KEY MESSAGES: In LBD, there is a specific distribution of CoMBs that is different from that in other neurodegenerative diseases. The increase of frontal CoMBs is not due to the frequently associated AD and CAA features but due to the LBD itself.",,"De Reuck, J. L.;Auger, F.;Durieux, N.;Cordonnier, C.;Deramecourt, V.;Lebert, F.;Leys, D.;Pasquier, F.;Maurage, C. A.;Bordet, R.",2015,,10.1159/000441057,0,
4711,Cobalt-55 positron emission tomography in vascular dementia: significance of white matter changes,"BACKGROUND: Vascular dementia (VaD) is still used as a covering term to indicate the relationship between cerebrovascular disease and the progressive cognitive disorder. The contribution of white matter changes (WMCs), seen with computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, to dementia had not been fully elucidated. Cobalt-55 (55Co) positron emission tomography (PET) allows us to distinguish between recent and old infarcts. PURPOSE: The present study investigates whether 55Co PET can detect the lesions responsible for the progression of the cognitive disorder in VaD patients. PATIENTS AND METHODS: 20 consecutive patients with a previous history of repeated strokes occurring more than 6 months before and with multiple cortical infarcts, lacunes and WMCs on CT and 5 age-matched controls were investigated with 55Co PET. The stroke patients were divided in two groups: 8 with and 12 without VaD. Average 55Co counts in cerebral cortex, deep gray nuclei and white matter were compared to the value in the cerebellum used as reference. RESULTS: In the control group, the 55Co uptake was identical in the cerebral cortex and in the cerebellum, but lower in the deep gray nuclei and the cerebral white matter. When comparing the stroke groups with the control, the 55Co uptake was similar for the cerebral cortex and deep gray nuclei, but significantly increased in the cerebral white matter. The 55Co uptake was also more increased in the stroke group with VaD compared to the non-demented group. CONCLUSION: 55Co PET shows that the WMCs are due to the ongoing damage of probably ischaemic origin which is more prominent in stroke patients with progressive cognitive decline.","Adult;Aged;Brain/pathology/radiography/ radionuclide imaging;Brain Infarction/pathology/radiography/ radionuclide imaging;Brain Ischemia/pathology/radiography/ radionuclide imaging;Cerebrovascular Circulation/ physiology;Cobalt Radioisotopes;Dementia, Vascular/pathology/radiography/ radionuclide imaging;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/pathology/radiography/ radionuclide imaging;Risk Factors;Tomography, Emission-Computed;Tomography, X-Ray Computed","De Reuck, J.;Santens, P.;Strijckmans, K.;Lemahieu, I.",2001,Dec 15,,0,
4712,Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates,"Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.",aged;amyotrophic lateral sclerosis;article;caudate nucleus;cerebrovascular disease;claustrum;controlled study;frontotemporal dementia;globus pallidus;human;human tissue;major clinical study;neurodegeneration with brain iron accumulation;nuclear magnetic resonance imaging;subthalamic nucleus;thalamus;topography,"De Reuck, J.;Devos, D.;Moreau, C.;Auger, F.;Durieux, N.;Deramecourt, V.;Pasquier, F.;Maurage, C. A.;Cordonnier, C.;Leys, D.;Bordet, R.",2017,,10.1007/s13760-017-0832-5,0,
4713,Prevalence of small cerebral bleeds in patients with a neurodegenerative dementia: a neuropathological study,"BACKGROUND: Small cerebral bleeds are frequently observed on magnetic resonance imaging in patients with Alzheimer dementia (AD). Histological confirmations in post-mortem brains are scarce. This study describes the prevalence of cerebrovascular lesions and the quantification of the ""bleeding load"" in post-mortem brains of patients with neurodegenerative dementias. PATIENTS AND METHODS: Forty-five brains of AD patients, 8 of dementia with Lewy bodies (DLB) and 12 of fronto-temporal dementia (FTD) were compared to 10 controls. Histological examination was performed for the evaluation of cerebral amyloid angiopathy (CAA), white matter changes (WMCs), micro-infarcts, and cerebral micro- and mini-bleeds (MnBs). The latter were evaluated semi-quantitatively on a coronal section of a whole cerebral hemisphere and on a horizontal section through the pons and cerebellum. RESULTS: Arterial hypertension (AH) was the main vascular risk factor in the patients with AD and DLB (P<0.05). MnBs, consisting of small perivascular bleeds, were significantly more frequent (P<0.001) in AD brains. They were mainly and equally present in the cerebral cortex of AD and DLB brains (P=0.04). Combined AD and DLB pathologies were present in 15%. CAA and WMCs occurred more frequently in AD brains (P<0.001). Occasional MnBs were observed in 60% of the controls. CONCLUSIONS: This neuropathological study confirms the frequent presence of MnBs and WMCs in AD brains. The relative high incidence of cortical MnBs in DLB brains is probably due to the high incidence of AH and the frequent association with AD and CAA.","Aged;Aged, 80 and over;Brain/blood supply/pathology;Cerebral Amyloid Angiopathy/complications/epidemiology/ pathology;Cerebral Hemorrhage/complications/epidemiology/ pathology;Dementia/complications/epidemiology/ pathology;Female;Humans;Hypertension/complications/pathology;Lewy Body Disease/complications/epidemiology/ pathology;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Prevalence;Risk Factors","De Reuck, J.;Deramecourt, V.;Cordonnier, C.;Leys, D.;Pasquier, F.;Maurage, C. A.",2011,Jan 15,10.1016/j.jns.2010.09.031,0,
4714,Superficial siderosis of the central nervous system: A post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates,"Background: Superficial siderosis (SS) is a rare finding on T2∗-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions. Materials and Methods: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases. Results: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03). Conclusions: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2∗-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.",,"De Reuck, J.;Deramecourt, V.;Cordonnier, C.;Auger, F.;Durieux, N.;Pasquier, F.;Bordet, R.;Defebvre, L.;Caparros-Lefebvre, D.;Maurage, C. A.;Leys, D.",2013,24,,0,
4715,Detection of microbleeds in post-mortem brains of patients with frontotemporal lobar degeneration: a 7.0-Tesla magnetic resonance imaging study with neuropathological correlates,"BACKGROUND: Microbleeds (MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration (FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*-weighted gradient-echo 7.0-T magnetic resonance imaging (MRI) in post-mortem FTLD brains. PATIENTS AND METHODS: The neuropathological and MRI findings in 12 FTLD brains were compared with eight age-matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere. RESULTS: Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls (P = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers (P < 0.01) and borderline increased in the middle cortical layers (P = 0.07) of the frontal section. CONCLUSIONS: Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood-brain barrier.","Adult;Age of Onset;Aged;Aged, 80 and over;Autopsy;Blood-Brain Barrier/pathology;Brain/ pathology;Cerebral Hemorrhage/ pathology;Female;Frontotemporal Lobar Degeneration/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged","De Reuck, J.;Deramecourt, V.;Cordonnier, C.;Auger, F.;Durieux, N.;Bordet, R.;Maurage, C. A.;Leys, D.;Pasquier, F.",2012,Oct,10.1111/j.1468-1331.2012.03776.x,0,
4716,Lobar intracerebral haematomas: Neuropathological and 7.0-tesla magnetic resonance imaging evaluation,Background and purpose The Boston criteria for cerebral amyloid angiopathy (CAA) need validation by neuropathological examination in patients with lobar cerebral haematomas (LCHs). In “vivo” 1.5-tesla magnetic resonance imaging (MRI) is unreliable to detect the age-related signal changes in LCHs. This post-mortem study investigates the validity of the Boston criteria in brains with LCHs and the signal changes during their time course with 7.0-tesla MRI. Materials and methods Seventeen CAA brains including 26 LCHs were compared to 13 non-CAA brains with 14 LCHs. The evolution of the signal changes with time was examined in 25 LCHs with T2 and T2* 7.0-tesla MRI. Results In the CAA group LCHs were predominantly located in the parieto-occipital lobes. Also white matter changes were more severe with more cortical microinfarcts and cortical microbleeds. On MRI there was a progressive shift of the intensity of the hyposignal from the haematoma core in the acute stage to the boundaries later on. During the residual stage the hyposignal mildly decreased in the boundaries with an increase of the superficial siderosis and haematoma core collapse. Conclusions Our post-mortem study of LCHs confirms the validity of the Boston criteria for CAA. Also 7.0-tesla MRI allows staging the age of the LCHs.,adult;aged;Alzheimer disease;article;autopsy;brain hematoma;comparative study;controlled study;disseminated intravascular clotting;female;frontal lobe;human;male;middle aged;neuropathology;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;occipital lobe;priority journal;siderosis;temporal lobe;vascular amyloidosis;very elderly;white matter;7.0-tesla MRI,"De Reuck, J.;Cordonnier, C.;Deramecourt, V.;Auger, F.;Durieux, N.;Leys, D.;Pasquier, F.;Maurage, C. A.;Bordet, R.",2016,,,0,
4717,Hippocampal microbleed on a post-mortem T(2)*-weighted gradient-echo 7.0-tesla magnetic resonance imaging?,"The present post-mortem study of a brain from an Alzheimer patient showed on a T(2)*-weighted gradient-echo 7.0-T MRI of a coronal brain section a hyposignal in the hippocampus, suggesting a microbleed. On the corresponding histological examination, only iron deposits around the granular cellular layer and in blood vessel walls of the hippocampus were observed without evidence of a bleeding. This case report illustrates that the detection of microbleeds on MRI has to be interpreted with caution. © 2011 S. Karger AG, Basel.",,"De Reuck, J.;Caparros-Lefebvre, D.;Deramecourt, V.;Maurage, C. A.",2011,2011,,0,
4718,The topography of cortical microbleeds in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance study,"INTRODUCTION: Cerebrovascular lesions are rare in frontotemporal lobar degeneration (FTLD), in contrast to other neurodegenerative diseases. Cortical microbleeds (CoMBs) are frequent in Alzheimer's disease, in particular in cases associated with cerebral amyloid angiopathy. The present study investigates the gyral topographic distribution of CoMBs in post-mortem FTLD brains with 7.0-tesla magnetic resonance imaging. MATERIAL AND METHODS: The distribution of CoMBs in 11 post-mortem FTLD brains and in 12 control brains was compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean values of CoMBs were determined in twenty-two different gyri. The findings were correlated to those separately observed on neuropathological examination. RESULTS: As a whole there was a trend of more CoMBs in the prefrontal section of FTLD as well as of the control brains. CoMBs were significantly increased in the superior frontal gyrus and the insular cortex (p </= 0.001) and also in the inferior frontal gyrus and the superior temporal gyrus (p </= 0.01). CONCLUSIONS: CoMBs in FTLD are only increased in the regions mainly affected by the neurodegenerative lesions. They probably do not reflect additional cerebrovascular disease.",,"De Reuck, J.;Auger, F.;Durieux, N.;Deramecourt, V.;Maurage, C. A.;Lebert, F.;Leys, D.;Cordonnier, C.;Pasquier, F.;Bordet, R.",2016,,,0,
4719,Frequency and topography of small cerebrovascular lesions in vascular and in mixed dementia: a post-mortem 7-tesla magnetic resonance imaging study with neuropathological correlates,"<i><b>Introduction</b>: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a ""pure"" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. <b>Material and methods</b>: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. <b>Results</b>: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. <b>Conclusions</b>: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. </i>.",cortical microbleeds;cortical microinfarcts;lacunar infarcts;mixed dementia;post-mortem 7.0-tesla MRI;topographic distribution of small cerebrovascular lesions;vascular dementia;white matter changes,"De Reuck, J.;Auger, F.;Durieux, N.;Deramecourt, V.;Maurage, C. A.;Cordonnier, C.;Pasquier, F.;Leys, D.;Bordet, R.",2017,,,0,
4720,Topography of Cortical Microbleeds in Alzheimer's Disease with and without Cerebral Amyloid Angiopathy: A Post-Mortem 7.0-Tesla MRI Study,"Cortical microbleeds (CMBs) detected on T2*-weighted gradient-echo (GRE) magnetic resonance imaging (MRI) are considered as a possible hallmark of cerebral amyloid angiopathy (CAA). The present post-mortem 7.0-tesla MRI study investigates whether topographic differences exist in Alzheimer's brains without (AD) and with CAA (AD-CAA). The distribution of CMBs in thirty-two post-mortem brains, consisting of 12 AD, 8 AD-CAA and 12 controls, was mutually compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean numbers of CMBs were determined in twenty-two different gyri. As a whole there was a trend of more CMBs on GRE MRI in the prefrontal section of the AD, the AD-CAA as well as of the control brains. Compared to controls AD brains had significantly more CMBs in the superior frontal, the inferior temporal, the rectus and the cinguli gyrus, and in the insular cortex. In AD-CAA brains CMBs were increased in all gyri with exception of the medial parietal gyrus and the hippocampus. AD-CAA brains showed a highly significant increase of CMBs in the inferior parietal gyrus (p value: 0.001) and a significant increase in the precuneus and the cuneus (p value: 0.01) compared to the AD brains. The differences in topographic distribution of CMBs between AD and AD-CAA brains should be further investigated on MRI in clinically suspected patients.",,"De Reuck, J.;Auger, F.;Durieux, N.;Deramecourt, V.;Cordonnier, C.;Pasquier, F.;Maurage, C. A.;Leys, D.;Bordet, R.",2015,Nov,10.14336/ad.2015.0429,0,
4721,Topographic distribution of white matter changes and lacunar infarcts in neurodegenerative and vascular dementia syndromes: A post-mortem 7.0-tesla magnetic resonance imaging study,"Background: White matter changes and lacunar infarcts are regarded as linked to the same underlying small-vessel pathology. On magnetic resonance imaging, white matter changes are frequently observed, while the number of lacunar infarcts is probably underestimated. The present study post-mortem 7.0-tesla magnetic resonance imaging study compares the severity and the distribution of white matter changes and lacunar infarcts in different neurodegenerative and vascular dementia syndromes in order to determine their impact on the disease evolution. Patients and methods: Eighty-four post-mortem brains consisting of 15 patients with pure Alzheimer’s disease and 12 with associated cerebral amyloid angiopathy, 14 patients with frontotemporal lobar degeneration, 7 with Lewy body dementia, 10 with progressive supranuclear palsy, 14 with vascular dementia and 12 control brains were examined. Six hemispheric coronal sections of each brain underwent 7.0-tesla magnetic resonance imaging. Location and severity of white matter changes and lacunar infarcts were evaluated semi-quantitatively in each section separately. Results: White matter changes predominated in the prefrontal and frontal sections of frontotemporal lobar degeneration and in the post-central section of associated cerebral amyloid angiopathy brains, while overall increased in vascular dementia cases. Lacunar infarcts were more frequent in the vascular dementia brains and mainly increased in the centrum semiovale. Conclusions: White matter changes have a different topographic distribution in neurodegenerative diseases and are most severe and extended in vascular dementia. Lacunar infarcts predominate in the deep white matter of vascular dementia compared to the neurodegenerative diseases. Vascular cognitive impairment is mainly linked to white matter changes due to chronic ischaemia as well as to lacunar infarcts due to small-vessel occlusion.",adult;aged;Alzheimer disease;article;autopsy;brain;centrum semiovale;controlled study;degenerative disease;diffuse Lewy body disease;disease association;disease severity;female;frontal cortex;frontotemporal dementia;hemisphere;human;human tissue;lacunar stroke;major clinical study;male;multiinfarct dementia;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;prefrontal cortex;priority journal;progressive supranuclear palsy;quantitative analysis;tissue distribution;topographic distribution;vascular amyloidosis;very elderly;white matter change;white matter lesion,"De Reuck, J.;Auger, F.;Durieux, N.;Cordonnier, C.;Deramecourt, V.;Pasquier, F.;Maurage, C. A.;Leys, D.;Bordet, R.",2016,,10.1177/2396987316650780,0,
4722,Comparison of 7.0-T T(2)*-magnetic resonance imaging of cerebral bleeds in post-mortem brain sections of Alzheimer patients with their neuropathological correlates,"BACKGROUND: In view of the increasing recognition of cerebral microbleeds (MCBs) with MRI, there is a need to validate their detection in post-mortem brains in patients with cerebrovascular diseases and dementia. MATERIALS AND METHODS: Out of 20 post-mortem brains of patients with Alzheimer dementia and with different cerebrovascular lesions, 45 large sections of the cerebral hemispheres, brainstem and cerebellum were submitted to a 7.0-T T(2)*-weighted MRI, and afterwards compared to the histological detection of haematomas, MCBs and mini-bleeds (MNBs). RESULTS: The sensitivity, specificity, predictive positive value and predictive negative value of the T(2)* imaging to detect MCBs and MNBs were excellent for those in the cortico-subcortical regions. There was a significant overestimation of MNBs in the striatum due to iron deposits unrelated to old haemorrhages. Also in the deep white matter, 42% of MNBs were not detected, while 31% of T(2)* hyposignals were not due to MNBs but to vessels filled with post-mortem thrombi. CONCLUSIONS: When evaluating the 'bleeding load' with 7.0-T T(2)*-weighted MRI in post-mortem brain sections of patients with dementia and vascular risk factors, only quantification of small cerebral bleeds in the cortico-subcortical regions is reliable.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology;Autopsy;Brain/ pathology;Cerebral Amyloid Angiopathy/pathology;Cerebral Arteries/pathology;Cerebral Hemorrhage/diagnosis/ pathology;Cerebrovascular Disorders/pathology;Female;Humans;Iron/metabolism;Magnetic Resonance Imaging/ methods;Male;Paraffin Embedding;Postmortem Changes;Predictive Value of Tests;Risk Factors;Thromboembolism/pathology","De Reuck, J.;Auger, F.;Cordonnier, C.;Deramecourt, V.;Durieux, N.;Pasquier, F.;Bordet, R.;Maurage, C. A.;Leys, D.",2011,,10.1159/000324391,0,
4723,Clinical significance of subcortical vascular disease in patients with mild cognitive impairment,"Patients with mild cognitive impairment (MCI) typically present with memory complaints. Some of these patients have subcortical vascular disease on computed tomography (CT) scan, namely white matter changes and lacunar infarcts, however it is not known whether these findings are associated with more pronounced cognitive deficits. In the present study we compare demographic, clinical and neuropsychological characteristics of MCI patients according to the presence or the absence of subcortical vascular disease. Forty consecutive patients with memory complaints, at least one neuropsychological memory test below 1 SD the normal for age and education, and maintained activities of daily living, were included. Patients with dementia, history of stroke or transient ischemic attack, or other brain disorders, were excluded. Twenty-five (62.5%) patients with MCI had no ischemic lesions on CT scan, and 15 (37.5%) were found to have subcortical vascular changes. MCI patients with subcortical vascular changes were older (77.1 ± 6.8 vs. 70.8 ± 7.5 years old), and more often males. The number of vascular risk factors, the frequency of neurological signs, the Hachinski score and the neuropsychological tests scores were not significantly different. The presence of subcortical vascular disease on CT scan is frequent in older patients with MCI, but does not appear to be associated with the severity of cognitive deficits.",age;aged;article;brain disease;brain infarction;brain ventricle;cerebrovascular disease;clinical article;clinical feature;cognitive defect;computer assisted tomography;controlled study;daily life activity;dementia;demography;disease association;education;female;human;male;memory disorder;neuropsychological test;priority journal;risk factor;sex difference;cerebrovascular accident;subcortical vascular disease;transient ischemic attack;white matter,"De Mendonça, A.;Ribeiro, F.;Guerreiro, M.;Palma, T.;Garcia, C.",2005,,,0,
4724,Alzheimer's disease: Longitudinal CT studies of ventricular change,"A 3-year longitudinal study was conducted with 50 Alzheimer's disease patients and 45 elderly control subjects. All study participants received an extensive evaluation that included brain CT at baseline and follow-up. Quantitation of ventricular size, using both linear and volume methods, revealed highly significant cross-sectional and longitudinal differences between the Alzheimer patients and control subjects. Specifically, the annual rate of change in ventricular volume was approximately 9% in the Alzheimer patients and approximately 2% in the controls. The presence of age-related white matter lesions had no effect on the clinical course of the patients or on the changes in ventricular size. Among the Alzheimer patients, the rate of clinical decline was strongly related to the rate of change in ventricular size. Baseline ventricular measurements were of no value in predicting the subsequent rate of clinical deterioration or ventricular enlargement. The results suggest that changes in ventricular size closely reflect the clinical changes in Alzheimer patients.",adult;aged;Alzheimer disease;brain ventricle;clinical article;computer analysis;computer assisted tomography;human;psychological aspect,"De Leon, M. J.;George, A. E.;Reisberg, B.;Ferris, S. H.;Kluger, A.;Stylopoulos, L. A.;Miller, J. D.;La Regina, M. E.;Chen, C.;Cohen, J.",1989,,,0,4725
4725,Alzheimer's disease: longitudinal CT studies of ventricular change,"A 3-year longitudinal study was conducted with 50 Alzheimer's disease patients and 45 elderly control subjects. All study participants received an extensive evaluation that included brain CT at baseline and follow-up. Quantitation of ventricular size, using both linear and volume methods, revealed highly significant cross-sectional and longitudinal differences between the Alzheimer patients and control subjects. Specifically, the annual rate of change in ventricular volume was approximately 9% in the Alzheimer patients and approximately 2% in the controls. The presence of age-related white matter lesions had no effect on the clinical course of the patients or on the changes in ventricular size. Among the Alzheimer patients, the rate of clinical decline was strongly related to the rate of change in ventricular size. Baseline ventricular measurements were of no value in predicting the subsequent rate of clinical deterioration or ventricular enlargement. The results suggest that changes in ventricular size closely reflect the clinical changes in Alzheimer patients.","Aged;Alzheimer Disease/*radiography;*Cerebral Ventriculography;Follow-Up Studies;Humans;Longitudinal Studies;Middle Aged;New York;*Tomography, X-Ray Computed","de Leon, M. J.;George, A. E.;Reisberg, B.;Ferris, S. H.;Kluger, A.;Stylopoulos, L. A.;Miller, J. D.;La Regina, M. E.;Chen, C.;Cohen, J.",1989,Jun,10.2214/ajr.152.6.1257,0,
4726,"PET-deoxyglucose, CT, and neuropathology of age-related white matter pathology in normals and Alzheimer's patients",,"Adult;Aged;Alzheimer Disease/*pathology;Blood Glucose/metabolism;Brain/*pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Deoxyglucose;Humans;Middle Aged;*Tomography, Emission-Computed;*Tomography, X-Ray Computed","de Leon, M. J.;George, A. E.;Kluger, A.;Franssen, E.;Ferris, S. H.;Wolf, A. P.",1989,Sep,,0,
4727,Regional correlation of PET and CT in senile dementia of the Alzheimer type,"Alzheimer disease is manifested by both widespread and regionally restricted brain changes, some of which have recently been identified in vivo with computed tomography (CT) and positron emission tomography (PET). This is a report of the regional correlation of CT and PET measurements in 19 carefully diagnosed subjects comprising 11 controls and eight patients with senile dementia of the Alzheimer type. Regional CT attenuation values did not discriminate between the two groups, but PET using 18F-2-deoxy-2-fluoro-D-glucose demonstrated significant regional reductions (range, 21%-28%) in glucose utilization in the Alzheimer group. PET measures were also more consistently related to cognitive decline. The correlation between CT structural measures and PET metabolic measures demonstrated consistent relations between widespread PET regions and CT changes in the thalamus, posterior limb of the internal capsule, and temporal lobes. However, CT changes in the frontal white matter, caudate nucleus, and anterior limb of the internal capsule were not related to any regional PET changes. These data support previous findings of temporal lobe involvement in Alzheimer disease and suggest the involvement of structures in the region of the third ventricle.","Aged;Alzheimer Disease/*diagnosis;Atrophy;Blood Glucose/*metabolism;Brain/metabolism;Caudate Nucleus/pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Corpus Striatum/pathology;Dementia/*diagnosis;Humans;Middle Aged;Thalamus/pathology;*Tomography, Emission-Computed;*Tomography, X-Ray Computed","de Leon, M. J.;George, A. E.;Ferris, S. H.;Rosenbloom, S.;Christman, D. R.;Gentes, C. I.;Reisberg, B.;Kricheff, II;Wolf, A. P.",1983,May-Jun,,0,
4728,"Interaction between hypertension, apoE, and cerebral white matter lesions","Background and Purpose - Cerebral white matter lesions (WMLs) are frequently found on magnetic resonance imaging scans in both cognitively intact and demented elderly persons. Vascular risk factors, especially hypertension, are related to their presence. However, not every person with vascular risk factors has WMLs, which suggests interaction with other determinants, eg, genetic factors. The ε4 allele of the apolipoprotein E gene (apoE) may be a candidate because this allele is associated with both the vascular risk factors and the consequences (cognitive impairment, dementia) of WMLs. Methods - We investigated apoE genotype, blood pressure levels, and their interaction in relation to subcortical and periventricular WMLs in 971 participants in the Rotterdam Scan Study. Results - ApoE ε4 carriers had a significantly higher subcortical WML volume than did apoE ε3ε3 carriers (adjusted mean difference, 0.5; 95% confidence interval, 0.2 to 0.8), irrespective of hypertension. This was not found for periventricular WMLs. Participants with both hypertension and at least 1 apoE ε4 allele had the highest degree of both types of WML; the interaction was statistically significant for subcortical WMLs (P=0.016). Conclusions - apoE ε4 carriers are at increased risk for WMLs if they suffer from hypertension as well. This may reflect a diminished capacity for neuronal repair in apoE ε4 carriers.",,"De Leeuw, F. E.;Richard, F.;De Groot, J. C.;Van Duijn, C. M.;Hofman, A.;Van Gijn, J.;Breteler, M. M. B.",2004,May,,0,
4729,White matter lesions are associated with progression of medial temporal lobe atrophy in Alzheimer disease,"BACKGROUND AND PURPOSE: Medial temporal lobe atrophy (MTA) is a hallmark of Alzheimer disease (AD). Its progression is often seen during the course of AD, but its frequency and risk factors remain unclear. METHODS: We investigated MTA in 35 patients with AD from whom sequential magnetic resonance imaging scans were available. White matter lesions (WML; for the periventricular [PV] and subcortical [SC] regions separately) and MTA were rated semiquantitatively. RESULTS: In approximately two thirds of all patients, progression of MTA was found. The mean MTA progression was 0.8 (standard deviation: 0.5) and 0.3 (standard deviation: 0.4) for patients with or without PVWML at baseline (P=0.01). Patients who showed progression of PVWML over the course of their disease had a significantly higher mean progression of MTA than those without PVWML progression (0.9 [SD: 0.4]) and 0.4 [SD: 0.5]; P=0.01). Patients with PVWML at baseline had a 40-fold increased risk for progression of MTA compared with those without baseline PVWML (odds ratio=40.0, 95% CI=1.3 to 1.2x10(3), P=0.03). Patients with progression of PVWML during the course of the disease had an increased risk for MTA progression (odds ratio=3.7 per unit increase of progression of PVWML, 95% CI=1.1 to 12.9, P=0.04). There was higher risk for progression of MTA for those with progression of PVWML than those without (odds ratio=10.9, 95% CI=1.0 to 122.5, P=0.05). This was not found for SCWML. CONCLUSIONS: Our findings suggest that the presence and the progression of WML are associated with progression of MTA in AD. WML may be a predictor of the course of the disease and a potential treatment target in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Atrophy;Brain/ pathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Risk Assessment;Temporal Lobe/ pathology","de Leeuw, F. E.;Korf, E.;Barkhof, F.;Scheltens, P.",2006,Sep,10.1161/01.STR.0000236555.87674.e1,0,
4730,Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease,"Cerebral MRI scanning frequently shows white matter lesions in elderly people. They are related to cognitive impairment and may result in dementia. Although vascular risk factors are associated with the presence of white matter lesions, the exact pathogenesis remains unclear. Animal studies have indicated involvement of endothelial cells in the pathogenesis of white matter lesions and possibly dementia. We investigated the relation between endothelial cell activation and white matter lesions in individuals with cerebrovascular disease. In 29 patients with an acute stroke (n = 11) or TIAs associated with a symptomatic internal carotid artery stenosis (n = 18), markers of endothelial cell activation such as intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and sP-selectin were measured by means of ELISA. All individuals underwent 1.5-T MRI scanning. White matter lesions were rated for the periventricular and the subcortical region separately. Individuals with severe periventricular white matter lesions had higher levels of sP-selectin (245.5 ng/mL vs. 172.7 ng/mL, p = 0.01) and sVCAM-1 (547.8 ng/mL vs. 454.0 ng/mL, p = 0.04) than those without. This association was only found in individuals with a symptomatic carotid artery stenosis. No such association was found for subcortical white matter lesions. We did not detect any relation between sICAM-1 and sE-selectin and white matter lesions. Endothelial cell activation may play a role in the pathogenesis of white matter lesions, especially in periventricular white matter. Possibly, this activation represents the influence of vascular factors on the cerebral endothelium as a prelude to increasingly severe small vessel disease.","Brain/*pathology;Brain Ischemia/pathology;Carotid Stenosis/pathology;Cerebrovascular Disorders/blood/diagnosis/*pathology;Diabetes Complications;Diabetes Mellitus/pathology;Endothelium, Vascular/*pathology;Female;Humans;Hypercholesterolemia/pathology;Hypertension/pathology;Ischemic Attack, Transient/pathology;Magnetic Resonance Imaging;Male;Middle Aged;P-Selectin/blood;Vascular Cell Adhesion Molecule-1/blood","de Leeuw, F. E.;de Kleine, M.;Frijns, C. J.;Fijnheer, R.;van Gijn, J.;Kappelle, L. J.",2002,Nov,,0,
4731,Cerebral white matter lesions in elderly people: Vascular risk factors and cognitive consequences,"With the advent of sensitive brain imaging techniques, white matter lesions are commonly observed in healthy as well as in demented elderly people. Primarily vascular risk factors have been related to the presence of white matter lesions, such as hypertension, atherosclerosis and atrial fibrillation. Subcortical white matter lesions are mainly associated with depression in the elderly, while periventricular lesions are clearly associated with cognitive dysfunction. Current evidence on the relation between vascular risk factors, white matter lesions and cognition is based on cross-sectional studies. Prospective studies are needed to confirm causality and to study the efficacy of treatment of vascular risk factors.",,"De Leeuw, F. E.;De Groot, J. C.;Van Gijn, J.",2001,27,,0,
4732,Hypertension and cerebral white matter lesions in a prospective cohort study,"White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hypertension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline.",antihypertensive agent;adult;aged;article;blood pressure measurement;brain cortex;brain injury;clinical trial;cognitive defect;controlled clinical trial;controlled study;dementia;disease association;disease duration;elderly care;female;follow up;human;hypertension;hypothalamus periventricular nucleus;major clinical study;male;nuclear magnetic resonance imaging;pathogenesis;priority journal;risk assessment;white matter,"De Leeuw, F. E.;De Groot, J. C.;Oudkerk, M.;Witteman, J. C. M.;Hofman, A.;Van Gijn, J.;Breteler, M. M. B.",2002,,,0,
4733,A follow-up study of blood pressure and cerebral white matter lesions,"White matter lesions are often observed on cerebral magnetic resonance imaging scans of elderly people and may play a role in the pathogenesis of dementia. Cross-sectional studies have shown an association between elevated blood pressure and white matter lesions. We prospectively studied the relation between blood pressure and white matter lesions in 1,077 subjects aged 60 to 90 years who were randomly sampled from two prospective population-based studies. One study had blood pressure measurements 20 years before, the other 5 years before. Overall response for the magnetic resonance imaging study was 63%, and declined from 73% among 60- to 70-year-olds to 48% for 80- to 90-year-olds. Diastolic and systolic blood pressure levels assessed 20 years before were significantly associated with subcortical and periventricular white matter lesions. The association between 20-year change in diastolic blood pressure and subcortical white matter lesions was J-shaped (relative risk, 2.2; 95% confidence interval, 1.0-5.2; and relative risk, 3.2; 95% confidence interval, 1.4-7.4, for decrease or increase of more than 10 mm Hg, respectively). The association between concurrent diastolic blood pressure level and white matter lesions was linear in subjects without, and J-shaped in subjects with, a history of myocardial infarction. Our results indicate that the J-shape relationship of diastolic blood pressure is not restricted to cardiovascular disease, but is also manifest in cerebrovascular disease.",,"De Leeuw, F. E.;De Groot, J. C.;Oudkerk, M.;Witteman, J. C. M.;Hofman, A.;Van Gijn, J.;Breteler, M. M. B.",1999,1999,,0,
4734,Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly,"BACKGROUND AND PURPOSE: MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. METHODS: We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531 subjects in late life. RESULTS: The presence of aortic atherosclerosis during midlife was significantly associated with the presence of periventricular white matter lesions approximately 20 years later (adjusted relative risk, 2.4; 95% CI, 1.2 to 5.0); the relative risks increased linearly with the severity of aortic atherosclerosis. No association was found between midlife aortic atherosclerosis and subcortical white matter lesions (adjusted relative risk, 1.1; 95% CI, 0.5 to 2.3) or between late-life aortic atherosclerosis and white matter lesions. CONCLUSIONS: The pathogenetic process that leads to cerebral periventricular white matter lesions starts already in or before midlife. The critical period for intervention directed at prevention of white matter lesions and its cognitive consequences may be long before these lesions become clinically detectable.","Age Factors;Aged;Aged, 80 and over;Aorta/pathology/physiopathology;Arteriosclerosis/*complications;Brain/pathology;Dementia/*etiology/pathology/physiopathology;Humans;Middle Aged;Risk Factors","de Leeuw, F. E.;De Groot, J. C.;Oudkerk, M.;Witteman, J. C.;Hofman, A.;van Gijn, J.;Breteler, M. M.",2000,Feb,,0,
4735,Atrial fibrillation and the risk of cerebral white matter lesions,"BACKGROUND: Cerebral white matter lesions are often observed on MRI scans of elderly nondemented and demented persons. Their pathogenesis is not fully understood but cerebral hypoperfusion may be involved. Atrial fibrillation is a common finding in elderly subjects and may lead to a reduced cardiac output with cerebral hypoperfusion. The authors investigated the association between atrial fibrillation and the presence of white matter lesions. METHODS: From 1995 through 1996, the authors randomly sampled 1077 subjects from two ongoing prospective population-based studies. From each participant, an electrocardiogram (ECG) was recorded; atrial fibrillation and left ventricular hypertrophy were diagnosed with a computer program. For one of the two groups (553 subjects), earlier ECGs were available (mean follow-up 4.7 years). All subjects underwent 1.5-T MRI scanning; white matter lesions were separately rated for the periventricular and subcortical regions. RESULTS: The prevalence of atrial fibrillation was 1.9% among subjects younger than 75 years and 5.5% in subjects older than 75 years. The total number of subjects with atrial fibrillation was 28. Subjects with atrial fibrillation had severe periventricular white matter lesions more than twice as often as subjects who did not (RR 2.2; 95% CI 1.0 to 5.2) but had no increased risk of subcortical white matter lesions (RR 1.1; 95% CI 0.4 to 2.6). For seven subjects with atrial fibrillation both at baseline and at follow up, these relative risks were 6.3 (95% CI 1.1 to 37.1) and 0.7 (95% CI 0.1 to 3.7). CONCLUSIONS: Atrial fibrillation is associated with periventricular white matter lesions, but not with subcortical white matter lesions.","Aged;Aged, 80 and over;Atrial Fibrillation/*diagnosis;Brain/pathology;Brain Ischemia/*diagnosis;Cerebral Ventricles/pathology;Dementia/*diagnosis;Electrocardiography;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors","de Leeuw, F. E.;de Groot, J. C.;Oudkerk, M.;Kors, J. A.;Hofman, A.;van Gijn, J.;Breteler, M. M.",2000,May 9,,0,
4736,Carotid atherosclerosis and cerebral white matter lesions in a population based magnetic resonance imaging study,"Cerebral white matter lesions are frequently observed on magnetic resonance imaging of elderly, nondemented persons. There is evidence that white matter lesions are involved in the pathophysiology of cognitive decline and dementia. White matter lesions can be divided into those in the periventricular and those in the subcortical region. Pathological and epidemiological studies suggest that atherosclerosis is involved in the pathogenesis of these lesions. Our study reports on the association between atherosclerosis in the carotid arteries and white matter lesions in a population-based study among 1077 elderly subjects. We randomly sampled 1077 subjects aged between 60-90 years from two prospective population-based studies. All subjects underwent ultrasonography of the carotid artery. In addition, 1.5 T magnetic resonance imaging was performed; white matter lesions in the subcortical and periventricular regions were rated separately. With increasing number of plaques in the carotid artery the severity of periventricular white matter lesions increased (Ptrend = 0.03), but not the severity of subcortical white matter lesions (Ptrend = 0.19). In addition, an increase in intima media thickness was borderline significantly associated with an increased severity of periventricular white matter lesions (Ptrend = 0.09), but not of subcortical white matter lesions (Ptrend = 0.68). These findings suggest that partly dissimilar pathogenetic mechanisms are involved in the etiology of periventricular and subcortical white matter lesions.",Aged;Brain/ pathology;Carotid Artery Diseases/ pathology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies,"de Leeuw, F. E.;de Groot, J. C.;Bots, M. L.;Witteman, J. C.;Oudkerk, M.;Hofman, A.;van Gijn, J.;Breteler, M. M.",2000,Apr,,0,
4737,Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study,"OBJECTIVE: White matter lesions are often seen on MR scans of elderly non-demented and demented people. They are attributed to degenerative changes of small vessels and are implicated in the pathogenesis of cognitive decline and dementia. There is evidence that especially periventricular white matter lesions are related to cognitive decline, whereas subcortical white matter lesions may be related to late onset depression. The frequency distribution of subcortical and periventricular white matter lesions according to age and sex reported. METHODS: A total of 1077 subjects aged between 60-90 years were randomly sampled from the general population. All subjects underwent 1.5T MR scanning; white matter lesions were rated separately for the subcortical region and the periventricular region. RESULTS: Of all subjects 8% were completely free of subcortical white matter lesions, 20% had no periventricular white matter lesions, and 5% had no white matter lesions in either of these locations. The proportion with white matter lesions increased with age, similarly for men and women. Women tended to have more subcortical white matter lesions than men (total volume 1.45 ml v 1. 29 ml; p=0.33), mainly caused by marked differences in the frontal white matter lesion volume (0.89 ml v 0.70 ml; p=0.08). Periventricular white matter lesions were also more frequent among women than men (mean grade 2.5 v 2.3; p=0.07). Also severe degrees of subcortical white matter lesions were more common in women than in men (OR 1.1; 95% confidence interval (95% CI) 0.8-1.5) and periventricular white matter lesions (OR 1.2; 95% CI 0.9-1.7), albeit that none of these findings were statistically significant. CONCLUSIONS: The prevalence and the degree of cerebral white matter lesions increased with age. Women tended to have a higher degree of white matter lesions than men. This may underlie the finding of a higher incidence of dementia in women than in men, particularly at later age.",Aged;Aging/pathology;Brain/ pathology;Brain Diseases/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Netherlands;Prevalence,"de Leeuw, F. E.;de Groot, J. C.;Achten, E.;Oudkerk, M.;Ramos, L. M.;Heijboer, R.;Hofman, A.;Jolles, J.;van Gijn, J.;Breteler, M. M.",2001,Jan,,0,
4738,Progression of cerebral white matter lesions in Alzheimer's disease: a new window for therapy?,"BACKGROUND: White matter lesions (WML) are a risk factor for Alzheimer's disease. Progression of WML is associated with vascular factors and cognitive decline in population based studies but the course of WML is unknown in Alzheimer's disease. OBJECTIVE: To investigate the prevalence and risk factors for progression of WML in Alzheimer's disease. SUBJECTS: 38 patients with Alzheimer's disease for whom blood pressure measurements and sequential brain MRIs were available. METHODS: The proportion of patients with progression of WML was calculated, stratified on baseline absence or presence of WML by analysis of variance. Odds ratios (OR) were calculated by age and sex adjusted logistic regression to quantify the relation between blood pressure and progression of WML. RESULTS: About 25% of the patients showed progression of WML. Patients with WML at baseline had significantly more progression than those without WML at baseline (adjusted mean difference = 1.2; 95% confidence interval (CI), 0.6 to 1.8). Diastolic blood pressure (DBP) was particularly related to progression of WML (OR = 5.9 (95% CI, 1.0 to 37.6) per 10 mm Hg DBP, p = 0.05). CONCLUSIONS: Alzheimer's disease patients with WML at baseline are at risk for rapid progression of WML. WML may offer a potential treatment target in this disease to ameliorate the rate of cognitive decline.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/*pathology;*Blood Pressure;Brain/*pathology;Cognition Disorders/*etiology;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Middle Aged;Prevalence;Risk Factors","de Leeuw, F. E.;Barkhof, F.;Scheltens, P.",2005,Sep,10.1136/jnnp.2004.053686,0,
4739,"Alzheimer's disease - One clinical syndrome, two radiological expressions: A study on blood pressure","Background: Vascular risk factors could play a role in the aetiology of Alzheimer's disease, but this has not been investigated in relation to neuroimaging findings Objective: To evaluate the distribution of blood pressure and an indicator of atherosclerosis (pulse pressure) in patients with Alzheimer's disease with and without small vessel disease. Methods: 152 Alzheimer patients underwent 1.0T MRI scanning. Blood pressure was measured with a sphygmomanometer. Small vessel disease was assessed by the presence of lacunar infarcts and white matter lesions. The distribution of blood pressure and pulse pressure, with or without small vessel disease, was assessed by linear regression analysis. Results: Patients with small vessel disease had a higher blood pressure, a wider pulse pressure, and an increased prevalence of hypertension. These findings were strongly age dependent: for patients under 65, mean systolic blood pressure was higher in the subpopulation with small vessel disease than in those without (mean (SD): 149.9 (19.3) v 135.7 (20.5) mm Hg; p = 0.02). Hypertension was more common in patients with white matter lesions than in those without (75.6% v 45.1%; p = 0.03) and the pulse pressure was higher (61.9 (14.4) v 51.7 (11.5) mm Hg; p = 0.01). There was no relation between blood pressure and the degree of (sub)cortical and hippocampal atrophy in patients without small vessel disease. Conclusions: There was heterogeneity in Alzheimer's disease patients with respect to blood pressure and pulse pressure. Alzheimer's disease encompasses a heterogeneous group of disorders which share a common cognitive profile but with distinct radiological features with respect to white matter lesions.",adult;aged;Alzheimer disease;article;blood pressure;brain atrophy;brain infarction;brain injury;controlled study;female;human;hypertension;intracranial pressure;linear regression analysis;major clinical study;male;nuclear magnetic resonance imaging;occlusive cerebrovascular disease;prevalence;priority journal;pulse pressure;sphygmomanometer;sphygmomanometry;statistical significance;systolic blood pressure,"De Leeuw, F. E.;Barkhof, F.;Scheltens, P.",2004,,,0,
4740,White matter lesions and hippocampal atrophy in Alzheimer's disease,"White matter lesions (WML) and hippocampal atrophy (HA) on MRI commonly co-occur in Alzheimer's disease (AD) and are thought to play a role in the etiology of AD. It is still not known whether WML and HA are independent or related. The authors investigated the relation between WML and HA in 179 patients with probable AD who had a cerebral MRI. A linear relation was found between WML and HA, especially for WML in the frontal and parieto-occipital regions. The results suggest that vascular pathology and typical AD pathology (HA) are related.",Aged;Alzheimer Disease/complications/*pathology;Atrophy;Brain Infarction/complications/pathology;Cerebral Cortex/*pathology;Female;Hippocampus/*pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/*pathology,"de Leeuw, F. E.;Barkhof, F.;Scheltens, P.",2004,Jan 27,,0,
4741,"Alzheimer's disease--one clinical syndrome, two radiological expressions: a study on blood pressure","BACKGROUND: Vascular risk factors could play a role in the aetiology of Alzheimer's disease, but this has not been investigated in relation to neuroimaging findings OBJECTIVE: To evaluate the distribution of blood pressure and an indicator of atherosclerosis (pulse pressure) in patients with Alzheimer's disease with and without small vessel disease. METHODS: 152 Alzheimer patients underwent 1.0T MRI scanning. Blood pressure was measured with a sphygmomanometer. Small vessel disease was assessed by the presence of lacunar infarcts and white matter lesions. The distribution of blood pressure and pulse pressure, with or without small vessel disease, was assessed by linear regression analysis. RESULTS: Patients with small vessel disease had a higher blood pressure, a wider pulse pressure, and an increased prevalence of hypertension. These findings were strongly age dependent: for patients under 65, mean systolic blood pressure was higher in the subpopulation with small vessel disease than in those without (mean (SD): 149.9 (19.3) v 135.7 (20.5) mm Hg; p = 0.02). Hypertension was more common in patients with white matter lesions than in those without (75.6% v 45.1%; p = 0.03) and the pulse pressure was higher (61.9 (14.4) v 51.7 (11.5) mm Hg; p = 0.01). There was no relation between blood pressure and the degree of (sub)cortical and hippocampal atrophy in patients without small vessel disease. CONCLUSIONS: There was heterogeneity in Alzheimer's disease patients with respect to blood pressure and pulse pressure. Alzheimer's disease encompasses a heterogeneous group of disorders which share a common cognitive profile but with distinct radiological features with respect to white matter lesions.",Age Factors;Aged;Alzheimer Disease/*complications/*pathology;Arteriosclerosis/*physiopathology;Atrophy;*Blood Pressure;Brain/*pathology;Female;Humans;Hypertension/complications/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Prevalence;Regression Analysis;Syndrome,"De Leeuw, F. E.;Barkhof, F.;Scheltens, P.",2004,Sep,10.1136/jnnp.2003.030189,0,4739
4742,Plasma vitamin B12 status and cerebral white-matter lesions,"BACKGROUND AND OBJECTIVE: Elevated homocysteine has been associated with a higher prevalence of cerebral white-matter lesions and infarcts, and worse cognitive performance. This raises the question whether factors involved in homocysteine metabolism, such as vitamin B(12), are also related to these outcomes. This study examined the association of several markers of vitamin B(12) status with cerebral white-matter lesions, infarcts and cognition. METHODS: The study evaluated the association of plasma concentrations of vitamin B(12), methylmalonic acid, holotranscobalamin and transcobalamin saturation with cerebral white-matter lesions and infarcts at baseline and cognition at baseline and during follow-up among 1019 non-demented elderly participants of the population-based Rotterdam Scan Study. Analyses were adjusted for several potential confounders, including homocysteine and folate concentration. RESULTS: Poorer vitamin B(12) status was significantly associated with greater severity of white-matter lesions, in particular periventricular white-matter lesions, in a concentration-related manner. Adjustment for common vascular risk factors (including blood pressure, smoking, diabetes and intima media thickness) did not alter the associations. Adjustment for homocysteine and folate modestly weakened the associations. No association was observed for any of the studied markers of vitamin B(12) status with presence of brain infarcts and baseline cognition or cognitive decline during follow-up. CONCLUSIONS: These results indicate that vitamin B(12) status in the normal range is associated with severity of white-matter lesions, especially periventricular lesions. Given the absence of an association with cerebral infarcts, it is hypothesised that this association is explained by effects on myelin integrity in the brain rather than through vascular mechanisms.",Aged;Biomarkers;Brain/*blood supply/metabolism/pathology;Cerebral Infarction/*blood/*diagnosis/epidemiology;Cerebrovascular Circulation/physiology;Cognition Disorders/diagnosis/epidemiology;Female;Folic Acid/blood;Homocysteine/metabolism;Humans;Magnetic Resonance Imaging;Male;Myelin Sheath/metabolism;Neuropsychological Tests;Population Surveillance;Prevalence;Risk Factors;Severity of Illness Index;Vitamin B 12/*blood,"de Lau, L. M.;Smith, A. D.;Refsum, H.;Johnston, C.;Breteler, M. M.",2009,Feb,10.1136/jnnp.2008.149286,0,
4743,Cerebral white matter lesions and lacunar infarcts contribute to the presence of mild parkinsonian signs,"BACKGROUND AND PURPOSE: Mild parkinsonian signs (MPS) are common in elderly people and may be an early stage of parkinson(ism). They might be related to cerebral small-vessel disease, although this association remains incompletely understood. To identify subjects at early stages of the disease, we investigated whether the presence of MPS was dependent on the severity and location of small-vessel disease, including white matter lesions and lacunar infarcts. METHODS: Four hundred thirty individuals, with small-vessel disease, aged between 50 and 85 years, without dementia or parkinsonism, were included in this analysis and underwent MRI scanning. The number and location of lacunar infarcts were rated. White matter lesion volume was assessed by manual segmentation with automated delineating of different regions. Presence of MPS was based on the motor section of the Unified Parkinson's Disease Rating Scale. Associations were determined using logistic regression analysis adjusted for age, sex, and total brain volume. RESULTS: Severe white matter lesions and the presence of lacunar infarcts were independently associated with the presence of MPS (OR, 2.6; 95% CI, 1.3-4.9 and OR, 1.8; 95% CI, 1.0-3.0). Frontal and parietal white matter lesions and, to a lesser extent, lacunar infarcts in the thalamus were associated with a higher risk of MPS. The presence of lacunar infarcts was independently related to the bradykinesia category of parkinsonian signs. CONCLUSIONS: This study shows that severe small-vessel disease, especially at certain locations, is associated with MPS signs in older adults. Our findings suggest that small-vessel disease interrupts basal ganglia-thalamocortical circuits involving both the frontal and parietal lobes and hence may result in MPS.","Aged;Aged, 80 and over;Basal Ganglia/pathology/physiopathology;Female;Humans;Leukoencephalopathies/*complications/pathology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Parkinson Disease/*epidemiology/physiopathology;Prevalence;Retrospective Studies;*Severity of Illness Index;Stroke, Lacunar/*complications/pathology;Thalamus/pathology/physiopathology","de Laat, K. F.;van Norden, A. G.;Gons, R. A.;van Uden, I. W.;Zwiers, M. P.;Bloem, B. R.;van Dijk, E. J.;de Leeuw, F. E.",2012,Oct,10.1161/strokeaha.112.657130,0,
4744,Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease,"Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities in white matter that may appear normal on brain imaging. The loss of integrity in such normal-appearing white matter may partly be due to small vessel disease and may play a role in causing gait disturbances. The white matter regions involved in these gait disturbances, both in white matter lesions and normal-appearing white matter, remain unclear. We, therefore, aimed to investigate the relation between the location of white matter lesions and gait using voxel-based morphometry analysis, as well as between white matter integrity and gait by applying tract-based spatial statistics to diffusion tensor imaging parameters. Magnetic resonance imaging was carried out on 429 individuals in the age range of 50 and 85 years, with cerebral small vessel disease without dementia or parkinsonism. Gait was assessed quantitatively. White matter lesions, especially in the centrum semiovale and periventricular frontal lobe, were related to a lower gait velocity, shorter stride length and broader stride width. Loss of white matter integrity, as indicated by a lower fractional anisotropy and higher mean diffusivity, in numerous regions was related to a lower gait performance. Most of these regions were located in the normal-appearing white matter. The strongest significant association was found in the corpus callosum, particularly the genu. Most of the associations in the normal-appearing white matter disappeared after controlling for white matter lesions and lacunar infarcts, except for some in the corpus callosum. In conclusion, our study showed that using a combination of voxel-based morphometry analysis of the white matter lesions and diffusion tensor imaging is of added value in investigating the pathophysiology of gait disturbances in subjects with small vessel disease. Our data demonstrate that, in elderly subjects with small vessel disease, widespread disruption of white matter integrity, predominantly in the normal-appearing white matter, is involved in gait disturbances. In particular, loss of fibres interconnecting bilateral cortical regions, especially the prefrontal cortex that is involved in cognitive control on motor performance, may be important. The most important mechanisms underlying affected normal-appearing white matter are probably a direct effect of small vessel disease or, indirectly, remote effects of white matter lesions and lacunar infarcts.","Aged;Aged, 80 and over;Anisotropy;Brain/ pathology;Cerebrovascular Disorders/complications/ pathology;Diffusion Tensor Imaging;Female;Gait;Gait Disorders, Neurologic/etiology/ pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology","de Laat, K. F.;Tuladhar, A. M.;van Norden, A. G.;Norris, D. G.;Zwiers, M. P.;de Leeuw, F. E.",2011,Jan,10.1093/brain/awq343,0,
4745,Response to treatment with corticoids in a case of inflammatory amyloid angiopathy without performing a biopsy,"Introduction: Inflammatory amyloid angiopathy (IAA) is an infrequent presenting symptom of the recently recognised cerebral amyloid angiopathy and its definitive diagnosis is reached by means of pathological analyses. Aim: We report the case of a male patient with IAA and good clinical, neuropsychological and neuroimaging response to treatment with corticoids; a biopsy of brain tissue was not considered necessary. Case report: The patient, 68 years old and diagnosed with Alzheimer's disease, suffered from generalised seizures followed by a language disorder and hemiparesis of the right-hand side. A magnetic resonance imaging scan showed a lesion displaying infiltrating behaviour in the left hemisphere and multiple instances of microbleeding. Clinical and radiological features suggested IAA and treatment was established with corticoids. Neuroimaging and neuropsychological tests revealed a notable improvement at 30 days after beginning treatment with immunosuppressants. The genotype was ApoE ε4/ε4. The need to perform a biopsy of brain tissue was ruled out. Conclusions: The case described here suggests that, in individualised cases with clinical and radiological features that are characteristic of IAA, it may be possible to establish an empirical treatment with corticoids with a probability diagnosis and perform a biopsy of brain tissue in the event of a lack of response to treatment, ́ 2012 Revista de Neurología.",,"de la Riva, P.;Moreno, F.;Carrera, N.;Barandiarán, M.;Arruti, M.;Martí-Massó, J. F.",2012,2012,,0,
4746,Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study,"There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study-specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151–164, 2017. © 2016 Wiley Periodicals, Inc.",age;aged;algorithm;allometry;article;automation;brain atrophy;brain region;brain size;cerebellum;controlled study;ethnicity;female;gray matter;human;image segmentation;major clinical study;male;neocortex;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;reproducibility;sex difference;statistical bias;white matter;1.5-T GE Signa Twinspeed EXCITE system,"de Jong, L. W.;Vidal, J. S.;Forsberg, L. E.;Zijdenbos, A. P.;Haight, T.;Sigurdsson, S.;Gudnason, V.;van Buchem, M. A.;Launer, L. J.",2017,,10.1002/hbm.23351,0,4747
4747,Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study,"There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study-specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.",Adni;AGES-Reykjavik;Cardia;Mri;allometry;brain;cortex;intra-cranial volume;striatum;thalamus;white matter,"de Jong, L. W.;Vidal, J. S.;Forsberg, L. E.;Zijdenbos, A. P.;Haight, T.;Sigurdsson, S.;Gudnason, V.;van Buchem, M. A.;Launer, L. J.",2016,Aug 25,10.1002/hbm.23351,0,
4748,Retinal vascular caliber and risk of dementia: the Rotterdam study,"BACKGROUND: Retinal vessels provide a unique opportunity to study both systemic and cerebrovascular disease. Smaller retinal arteriolar calibers are strongly related to hypertension, whereas larger retinal venular calibers are more related to inflammation, cerebral hypoperfusion, and cerebrovascular disease. Whether retinal vessel calibers are related to dementia remains unclear. METHODS: We investigated whether retinal arteriolar and venular calibers are associated with risk of dementia, and its subtypes Alzheimer disease (AD) and vascular dementia, in the prospective population-based Rotterdam Study. Digitized retinal images were available in 5,553 participants aged 55 years or over and dementia-free at baseline (1990-1993). Participants were re-examined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia. RESULTS: During a mean follow-up of 11.6 years, 655 participants developed dementia. AD was diagnosed in 519 and vascular dementia in 73 participants. Larger venular calibers were associated with an increased risk of dementia, in particular vascular dementia (age- and sex-adjusted hazard ratio per SD increase: 1.31; 95% confidence interval 1.06-1.64), but not AD. The association remained significant after adjustment for stroke and cardiovascular risk factors. Smaller arteriolar calibers were also associated with an increased risk of vascular dementia, yet only when adjusted for venular calibers. CONCLUSIONS: Retinal venular widening is associated with an increased risk of vascular dementia. Our findings are in line with previous observations in stroke and cerebral small-vessel disease and suggest that the association between larger retinal venular calibers and dementia may reflect cerebral hypoperfusion and subsequent ischemia.","Aged;Aged, 80 and over;Alzheimer Disease/ epidemiology/ pathology;Cohort Studies;Dementia, Vascular/ epidemiology/ pathology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Netherlands/epidemiology;Population Surveillance/methods;Prospective Studies;Retinal Vessels/ pathology;Risk Factors","de Jong, F. J.;Schrijvers, E. M.;Ikram, M. K.;Koudstaal, P. J.;de Jong, P. T.;Hofman, A.;Vingerling, J. R.;Breteler, M. M.",2011,Mar 1,10.1212/WNL.0b013e31820e7baa,0,
4749,Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia,"Background: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. Objective: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular origin (ie, white matter lesions and infarcts) and findings more specifically found in early Alzheimer disease (ie, hippocampal and amygdalar atrophy). Design: In a population-based sample of 1074 older persons without dementia (aged 60-90 y), we made brain MRIs from which we rated white matter lesions and brain infarcts. In a subset of 509 people, hippocampal and amygdalar volumes on MRI were measured. Alcohol intake was assessed by using a structured questionnaire. We categorized alcohol intake as lifetime abstention and very light (<1 drink/wk), light (≥1 drink/wk to <1 drink/d), moderate (≥1 drink/d to <4 drinks/d), and heavy (≥4 drinks/d) intakes. Results: Persons whose alcohol consumption was light to moderate had less severe white matter lesions and brain infarcts on MRI than did abstainers or heavy drinkers. Abstainers and very light drinkers had smaller hippocampal and amygdalar volumes on MRI than did light-to-moderate drinkers, but only if the former carried an apolipoprotein (APOE) ε4 allele. Conclusion: Light-to:moderate alcohol intake is associated with a lower prevalence of vascular brain findings and, in APOE ε4 carriers, hippocampal and amygdalar atrophy on MRI. © 2004 American Society for Clinical Nutrition.",,"De Heijer, T.;Vermeer, S. E.;Van Dijk, E. J.;Prins, N. D.;Koudstaal, P. J.;Van Duijn, C. M.;Hofman, A.;Breteler, M. M. B.",2004,October,,0,
4750,Loss of venous integrity in cerebral small vessel disease: a 7-T MRI study in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"BACKGROUND AND PURPOSE: Previous pathological studies in humans or in animal models have shown alterations of small arteries and veins within white matter lesions in cerebral small vessel disease. We aimed to evaluate in vivo, the integrity of the cerebral venous network using high-resolution MRI both within and outside white matter hyperintensities in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: High-resolution T2*-weighted images were obtained at 7-T in 13 CADASIL patients with no or only mild symptoms and 13 age- and sex-matched controls. Macroscopic veins were automatically counted in the centrum semiovale and compared between patients and controls. In addition, T2* was compared between groups in the normal-appearing white matter. RESULTS: Vein density was found lower in CADASIL patients compared with that in controls (-14.6% in patients, P<0.001). This was detected both within and outside white matter hyperintensities. Mean T2*, that is presumably inversely related to the venous density, was also found increased in normal-appearing white matter of patients (+7.2%, P=0.006). All results were independent from the extent of white matter hyperintensities. CONCLUSIONS: A significant reduction in the number of visible veins was observed in the centrum semiovale of CADASIL patients both within and outside white matter hyperintensities, together with an increase of T2* in the normal-appearing white matter. Additional studies are needed to decipher the exact implication of such vasculature changes in the appearance of white matter lesions.",Adult;Aged;CADASIL/ pathology/physiopathology;Cerebral Veins/ pathology/physiopathology;Cerebrum/ pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging/ instrumentation/methods;Male;Middle Aged,"De Guio, F.;Vignaud, A.;Ropele, S.;Duering, M.;Duchesnay, E.;Chabriat, H.;Jouvent, E.",2014,Jul,10.1161/strokeaha.114.005726,0,
4751,In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL,"BACKGROUND AND PURPOSE: Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale </=1 and Mini Mental State Examination (MMSE) >/=24). METHODS: Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1+/-13.2 years, 36% male) and 24 controls (54.8+/-11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. RESULTS: MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. CONCLUSIONS: Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.",Adult;CADASIL/ pathology;Case-Control Studies;Cerebral Cortex/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Organ Size,"De Guio, F.;Reyes, S.;Vignaud, A.;Duering, M.;Ropele, S.;Duchesnay, E.;Chabriat, H.;Jouvent, E.",2014,,10.1371/journal.pone.0106311,0,
4752,Decreased T1 contrast between gray matter and normal-appearing white matter in CADASIL,"BACKGROUND AND PURPOSE: CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects. MATERIALS AND METHODS: Contrast between gray matter and normal-appearing white matter was assessed by using histogram analyses of 3D T1 high-resolution MR imaging in 23 patients with CADASIL at the initial stage of the disease (Mini-Mental State Examination score > 24 and modified Rankin scale score </= 1; mean age, 53.5 +/- 11.1 years) and 30 age- and sex-matched controls. RESULTS: T1 contrast between gray matter and normal-appearing white matter was significantly reduced in patients compared with age- and sex-matched controls (patients: 1.35 +/- 0.08 versus controls: 1.43 +/- 0.04, P < 10(-5)). This reduction was mainly driven by a signal decrease in normal-appearing white matter. Contrast loss was strongly related to the volume of white matter hyperintensities. CONCLUSIONS: Conventional 3D T1 imaging shows significant loss of contrast between gray matter and normal-appearing white matter in CADASIL. This probably reflects tissue changes in normal-appearing white matter outside signal abnormalities on T2 or FLAIR sequences. These contrast alterations should be taken into account for image interpretation and postprocessing.","Adult;Aged;Brain/ pathology;CADASIL/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology","De Guio, F.;Reyes, S.;Duering, M.;Pirpamer, L.;Chabriat, H.;Jouvent, E.",2014,Jan,10.3174/ajnr.A3639,0,
4753,White matter edema at the early stage of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"BACKGROUND AND PURPOSE: Recently, in a mouse model of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a monogenic cerebral small vessel disease, intramyelinic edema was detected in the white matter (WM) early during the course of the disease. We hypothesized that if this mechanism holds true in patients, it would translate in larger WM volume. We aimed to measure WM volume in patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy in comparison with age- and sex-matched controls, along with the ratio of cortical surface area to the volume of brain hemispheres as an indirect measure that should be reduced in patients. METHODS: Twenty patients at the early stage of the disease (Mini Mental State Examination >24 and modified Rankin scale </=1) and 27 age- and sex-matched controls had high-quality 3-Tesla 3DT1 MRI acquisitions. Volumes of brain hemispheres and of WM were determined. The ratio of cortical surface area to the volume of brain hemispheres was evaluated as a proxy of underlying WM volume. RESULTS: Patients had larger volumes of WM than controls (patients: 479.4+/-71.7; controls: 463.9+/-44.2; P=0.03). They presented a lower cortical surface area and cortical volume leading to a lower ratio of cortical surface area to the volume of brain hemispheres (patients: 15.7+/-0.7; controls: 16.1+/-0.5; P=0.004). Volume of WM tended to be associated with that of WM hyperintensities (P=0.06). CONCLUSIONS: Patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy have larger WM volume than age- and sex-matched controls, a finding compatible with the hypothesis of intramyelinic edema as observed recently in mice.",Adult;Aged;Brain Edema/*pathology;CADASIL/*pathology;Case-Control Studies;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size;White Matter/*pathology;Cadasil;cerebral small vessel diseases;edema;white matter diseases,"De Guio, F.;Mangin, J. F.;Duering, M.;Ropele, S.;Chabriat, H.;Jouvent, E.",2015,Jan,10.1161/strokeaha.114.007018,0,
4754,White Matter Degeneration with Aging: Longitudinal Diffusion MR Imaging Analysis,"Purpose To determine longitudinally the rate of change in diffusion-tensor imaging (DTI) parameters of white matter microstructure with aging and to investigate whether cardiovascular risk factors influence this longitudinal change. Materials and Methods This prospective population-based cohort study was approved by a dedicated ethics committee overseen by the national government, and all participants gave written informed consent. Community-dwelling participants without dementia were examined by using a research-dedicated 1.5-T magnetic resonance (MR) imager on two separate visits that were, on average, 2.0 years apart. Among 810 persons who were eligible for imaging at baseline, longitudinal imaging data were available for 501 persons (mean age, 69.9 years; age range, 64.1-91.1 years). Changes in normal-appearing white matter DTI characteristics in the tract centers were analyzed globally to investigate diffuse patterns of change and then locally by using voxelwise multilinear regression. The influence of cardiovascular risk factors was assessed by treating them as additional determinants in both analyses. Results Over the 2.0-year follow-up interval, global fractional anisotropy (FA) decreased by 0.0042 (P < .001), while mean diffusivity (MD) increased by 8.1 x 10(-6) mm(2)/sec (P < .001). Voxelwise analysis of the brain white matter skeleton showed an average decrease of 0.0082 (Pmean = .002) in FA in 57% of skeleton voxels. The sensorimotor pathway, however, showed an increase of 0.0078 (Pmean = .009) in FA. MD increased by 10.8 x 10(-6)mm(2)/sec (Pmean < .001) on average in 79% of white matter skeleton voxels. Additionally, white matter degeneration was more pronounced in older persons. Cardiovascular risk factors were generally not associated with longitudinal changes in white matter microstructure. Conclusion Longitudinal diffusion analysis indicates widespread microstructural deterioration of the normal-appearing white matter in normal aging, with relative sparing of sensorimotor fibers. ((c)) RSNA, 2015 Online supplemental material is available for this article.",,"de Groot, M.;Cremers, L. G.;Ikram, M. A.;Hofman, A.;Krestin, G. P.;van der Lugt, A.;Niessen, W. J.;Vernooij, M. W.",2016,May,10.1148/radiol.2015150103,0,
4755,Cerebral white matter lesions and subjective cognitive dysfunction: The Rotterdam scan study,"Objective: To determine the relationship between cerebral white matter lesions (WML) and subjective cognitive dysfunction. Background: Subjective cognitive dysfunction is present when a person perceives failures of cognitive function. When annoying enough, these failures will be expressed as complaints. Subjective cognitive dysfunction may be a prelude to or coincide with objective cognitive impairment. WML have been related to objective cognitive impairment and dementia, but their relationship with subjective cognitive dysfunction is not clear. Previous population-based studies on the latter relationship have been limited in sample size, recording of subjective cognitive function, and assessment of WML severity. Methods: We randomly sampled 1,049 elderly nondemented participants from the general population. Data on subjective cognitive dysfunction and its progression were derived from a 15-item questionnaire. Objective cognitive performance was assessed using a series of neuropsychological tests. WML were scored on MRI for periventricular and subcortical regions separately. Results: WML were associated with more subjective cognitive failures. WML were more severe for participants reporting progression of these failures compared with participants without these failures, especially within participants with better than average cognitive performance (p = 0.008, for periventricular WML). Participants with severe WML reported progression of cognitive failures more than twice as often than did those with little or no WML. The relationship between the severity of WML and subjective cognitive failures was present for periventricular and subcortical WML. Conclusions: WML are associated with subjective cognitive failures and in particular with reporting progression of these failures, even in the absence of objective cognitive impairment.",adolescent;adult;aged;article;brain injury;child;clinical trial;cognition;cognitive defect;controlled clinical trial;controlled study;depression;disease association;disease course;disease severity;female;human;major clinical study;male;neuropsychological test;nuclear magnetic resonance imaging;preschool child;priority journal;questionnaire;randomized controlled trial;school child;scoring system;white matter,"De Groot, J. C.;De Leeuw, F. E.;Oudkerk, M.;Hofman, A.;Jolles, J.;Breteler, M. M. B.",2001,,,0,
4756,Subcortical arteriosclerotic encephalopathy: single photon emission computed tomography-magnetic resonance imaging correlation,"Regional cerebral blood flow was studied using 99mTc-HM-PAO and single photon emission computed tomography (SPECT) in five healthy subjects and in eight patients with clinical and computed tomography (CT) features of subcortical arteriosclerotic encephalopathy. All the patients and controls underwent magnetic resonance imaging (MRI). Circumscribed cortical hypoperfusion was observed in three patients, and in one case there was no evidence of cortical or sulcal alterations on MRI. In all the patients, a reduction of the white matter perfusion was found in periventricular and/or supraventricular regions. This pattern was substantially correlated with the typical white matter hyperintensities shown by MRI scans. These findings support the hypothesis that white matter hypoperfusion is the most prominent functional abnormality in subcortical arteriosclerotic encephalopathy.","Aged;Brain/ pathology/radionuclide imaging;Cerebrovascular Circulation/physiology;Dementia/ diagnosis;Demyelinating Diseases/ diagnosis;Female;Humans;Intracranial Arteriosclerosis/ diagnosis;Magnetic Resonance Imaging;Male;Organotechnetium Compounds;Oximes;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","De Cristofaro, M. T.;Mascalchi, M.;Pupi, A.;Nencini, P.;Formiconi, A. R.;Inzitari, D.;Dal Pozzo, G.;Meldolesi, U.",1990,,,0,
4757,High-resolution nuclear magnetic resonance imaging and single photon emission computerized tomography. Cerebral blood flow in a case of pure sensory stroke and mild dementia owing to subcortical arteriosclerotic encephalopathy (Binswanger's disease),"Pure sensory stroke (PSS) is typically caused by a lacunar infarct located in the ventral-posterior (VP) thalamic nucleus contralateral to the paresthetic symptoms. The lesion is usually so small that it cannot be seen on computerized tomography (CT), as illustrated by our case. In our moderately hypertensive, 72- year-old patient with PSS, CT scanning and conventional nuclear magnetic resonance imaging (NMRI) scanning using a 7-mm-thick slice on a 1.5 Tesla instrument all failed to visualize the thalamic infarct. Using the high-resolution mode with 2-mm slice thickness it was, however, clearly seen. In addition, NMRI unexpectedly showed diffuse periventricular demyelinization as well as three other lacunar infarcts, i.e., findings characteristic of subcortical arteriosclerotic encephalopathy (SAE). This prompted psychometric testing, which revealed signs of mild (subclinical) dementia, in particular involving visiospatial apraxia; this pointed to decreased function of the right parietal cortex, which was structurally intact on CT and NMRI. Single photon emission computerized tomography by Xenon-133 injection and by hexamethyl-propyleneamine-oxime labeled with Technetium-99m showed asymmetric distribution of cerebral blood flow (CBF), with an 18% lower value in the right parietal cortex compared to the left side; this indicated asymmetric disconnection of the cortex by the SAE. Thus, the tomograms of the functional parameter, CBF, correlated better with the deficits revealed by neuropsychological testing than by CT or NMRI.",,"De Chiara, S.;Lassen, N. A.;Andersen, A. R.;Gade, A.;Lester, J.;Thomsen, C.;Henriksen, O.",1987,1987,,0,
4758,Functional brain imaging with I123-amphetamine. First experience in the Netherlands,"Single Photon Emission Computed Tomography (SPECT) has been used in the last five years as a method for cerebral bloodflow imaging, especially in cerebral infarction. In this study the first experiences in the Netherlands are presented. In 57.6% of our patients lesions, defined by SPECT were larger than those found by CT. This was not only seen in patients with cerebral infarction but also in hematoma. In 33.3% the size of the lesions were comparable. In 10 out of 14 patients with a solitary lesion in one hemisphere a decreased perfusion was seen in the contralateral cerebellar hemisfere. This phenomenon is called crossed cerebellar diaschisis. One patient with probably Alzheimer disease, showing a specific flowpattern, is discussed.",,"De Bruine, J. F.;Van Royen, E. A.;Van Weeren, F.",1986,1986,,0,
4759,The big imitator strikes again: a case report of neurosyphilis in a patient with newly diagnosed HIV,"BACKGROUND: Neurosyphilis is the result of an infection of the central nervous system caused by the spirochete Treponema pallidum. Its clinical presentation includes meningovascular syphilis, tabes dorsalis, and dementia paralytica, resulting in a wide range of symptoms such as psychosis, Parkinsonism, and depression. CASE REPORT: A 49-year-old male was admitted to a psychiatric hospital because of social withdrawal and self-neglect, indicative of a major depression. A routine HIV-test was positive and resulted in an admission to the Antwerp University Hospital. Clinical examination showed Argyll Robertson pupils, a wide-based gait, absence of vibration sense in the lower limbs, and a MMSE-score of 25/30. Blood analysis revealed a CD4+ count of 99 cells/muL and a HIV viral load of 2,13 x 10(5) copies/mL plasma. A serum TPHA (T. pallidum hemagglutination assay) titre of 1/20480 and RPR (rapid plasma reagin) titre of 1/128 were detected. TPHA and RPR titre in the cerebrospinal fluid were, respectively, 1/10240 and 1/4. A brain MRI showed diffuse cortical atrophy and lesions in the white matter compatible with HIV-encephalopathy. The diagnoses of advanced HIV-infection and late neurosyphilis were made. HAART (highly active antiretroviral therapy) and high-dose IV penicillin G were started. CONCLUSION: In all patients with new-onset dementia or untreatable psychosis, neurosyphilis should always be considered. Argyll Robertson pupils are regarded as pathognomonic of neurosyphilis. The management of neurosyphilis includes high-dose IV benzyl penicillin for 10 to 14 days. Close follow-up including a lumbar puncture after 6 months is warranted to ensure treatment recovery.",Argyll Robertson pupils;HIV-encephalopathy;Neurosyphilis;Rapid plasma reagin;Treponema pallidum hemagglutination assay,"de Bruijn, S.;Kenyon, C.;Leonard, N.;Vlieghe, E.",2017,Oct,,0,
4760,The big imitator strikes again: a case report of neurosyphilis in a patient with newly diagnosed HIV,"BACKGROUND: Neurosyphilis is the result of an infection of the central nervous system caused by the spirochete Treponema pallidum. Its clinical presentation includes meningovascular syphilis, tabes dorsalis, and dementia paralytica, resulting in a wide range of symptoms such as psychosis, Parkinsonism, and depression. CASE REPORT: A 49-year-old male was admitted to a psychiatric hospital because of social withdrawal and self-neglect, indicative of a major depression. A routine HIV-test was positive and resulted in an admission to the Antwerp University Hospital. Clinical examination showed Argyll Robertson pupils, a wide-based gait, absence of vibration sense in the lower limbs, and a MMSE-score of 25/30. Blood analysis revealed a CD4+ count of 99 cells/muL and a HIV viral load of 2,13 x 105 copies/mL plasma. A serum TPHA (T. pallidum hemagglutination assay) titre of 1/20480 and RPR (rapid plasma reagin) titre of 1/128 were detected. TPHA and RPR titre in the cerebrospinal fluid were, respectively, 1/10240 and 1/4. A brain MRI showed diffuse cortical atrophy and lesions in the white matter compatible with HIV-encephalopathy. The diagnoses of advanced HIV-infection and late neurosyphilis were made. HAART (highly active antiretroviral therapy) and high-dose IV penicillin G were started. CONCLUSION: In all patients with new-onset dementia or untreatable psychosis, neurosyphilis should always be considered. Argyll Robertson pupils are regarded as pathognomonic of neurosyphilis. The management of neurosyphilis includes high-dose IV benzyl penicillin for 10 to 14 days. Close follow-up including a lumbar puncture after 6 months is warranted to ensure treatment recovery.",Argyll Robertson pupils;HIV-encephalopathy;Neurosyphilis;Rapid plasma reagin;Treponema pallidum hemagglutination assay,"de Bruijn, S.;Kenyon, C.;Leonard, N.;Vlieghe, E.",2017,Feb 21,,0,4759
4761,Subclinical cardiac dysfunction increases the risk of stroke and dementia: the Rotterdam Study,"OBJECTIVE: To investigate the association between cardiac function and the risk of stroke and dementia in elderly free of clinical cardiac disease. Additionally, we investigated the relation between cardiac function and MRI markers of subclinical cerebrovascular disease. METHODS: This study was conducted within the population-based Rotterdam Study. A total of 3,291 participants (60.8% female, age-range 58-98 years) free of coronary heart disease, heart failure, atrial fibrillation, stroke, and dementia underwent echocardiography in 2002-2005 to measure cardiac function. Follow-up finished in 2012. In 2005-2006, a random subset of 577 stroke-free people without dementia underwent brain MRI on which infarcts and white matter lesion volume were assessed. RESULTS: During 21,785 person-years of follow-up, 164 people had a stroke and during 19,462 person-years of follow-up, 208 people developed dementia. Measures of better diastolic function, such as higher E/A ratio, were associated with a lower risk of stroke (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.69; 0.98) and dementia (HR 0.82; 95% CI 0.70; 0.96). Better systolic function, measured as higher fractional shortening, was only associated with a lower risk of stroke (HR 0.84; 95% CI 0.72; 0.98). Better diastolic function was related to a lower prevalence of silent infarcts on MRI, especially lacunar infarcts. CONCLUSIONS: In elderly free of clinical cardiac disease, worse diastolic function is associated with clinical stroke, dementia, and silent infarcts on MRI, whereas worse systolic function is related only to clinical stroke. These findings can form the basis for future research on the utility of cardiac function as potential intervention target for prevention of neurologic diseases.","Aged;Aged, 80 and over;Cardiovascular Diseases/*diagnosis/*epidemiology;Cohort Studies;Dementia/*diagnosis/*epidemiology;Female;Follow-Up Studies;Humans;Male;Middle Aged;Netherlands/epidemiology;Population Surveillance/methods;Prospective Studies;Risk Factors;Stroke/*diagnosis/*epidemiology","de Bruijn, R. F.;Portegies, M. L.;Leening, M. J.;Bos, M. J.;Hofman, A.;van der Lugt, A.;Niessen, W. J.;Vernooij, M. W.;Franco, O. H.;Koudstaal, P. J.;Ikram, M. A.",2015,Feb 24,10.1212/wnl.0000000000001289,0,
4762,"Determinants, MRI correlates, and prognosis of mild cognitive impairment: the Rotterdam Study","Mild cognitive impairment (MCI) marks a transitional stage between healthy aging and dementia, but the understanding of MCI in the general population remains limited. We investigated determinants, MRI-correlates, and prognosis of MCI within the population-based Rotterdam Study. Firstly, we studied age, APOE-epsilon4 carriership, waist circumference, hypertension, diabetes mellitus, total and HDL-cholesterol levels, smoking, and stroke as potential determinants of MCI. Determinants were assessed cross-sectionally at baseline (2002-2005) and up to 7 years prior to baseline (1997-2001). Secondly, we compared volumetric, microstructural, and focal MRI-correlates in persons with and without MCI. Thirdly, we followed participants for incident dementia and mortality until 2012. Out of 4,198 participants, 417 had MCI, of whom 163 amnestic and 254 non-amnestic MCI. At baseline, older age, APOE-epsilon4 carriership, lower total cholesterol levels, and stroke were associated with MCI. Additionally, lower HDL-cholesterol levels and smoking were related to MCI when assessed 7 years prior to baseline. Persons with MCI, particularly those with non-amnestic MCI, had larger white matter lesion volumes, worse microstructural integrity of normal-appearing white matter, and a higher prevalence of lacunes, compared to cognitively healthy participants. MCI was associated with an increased risk of dementia (hazard ratio (HR) 3.98, 95% confidence interval (CI) 2.97;5.33), Alzheimer's disease (HR 4.03, 95% CI 2.92;5.56), and mortality (HR 1.54, 95% CI 1.28;1.85). In conclusion, we found that several vascular risk factors and MRI-correlates of cerebrovascular disease were related to MCI in the general population. Participants with MCI had an increased risk of dementia, including Alzheimer's disease, and mortality.","Aged;Aged, 80 and over;Apolipoprotein E4/genetics;Brain/ pathology;Community Health Planning;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/ epidemiology/genetics/mortality;Netherlands/epidemiology;Neuropsychological Tests;Prognosis;Retrospective Studies;Risk Factors","de Bruijn, R. F.;Akoudad, S.;Cremers, L. G.;Hofman, A.;Niessen, W. J.;van der Lugt, A.;Koudstaal, P. J.;Vernooij, M. W.;Ikram, M. A.",2014,,10.3233/jad-132558,0,
4763,Frontoparietal cortical atrophy with gliosis in the gray matter of cerebral cortex: case report,"The case of a patient who suffered from progressive amnesia, depressive humor, language and visuospatial disturbances, and hallucination episodies with interference at the daily living activities is reported. She had moderate neuropsychological diffuse deficits at the first examination, especially at the executive and visuo-constructive functions. Her cerebrospinal fluid test presented high total protein. Magnetic resonance image showed slight white matter increase in periventricular, semi-oval center bilateral and left external capsule regions, besides light frontal and parietal lobe atrophy, bilaterally. Brain single photon emission computerized tomography revealed both a bilateral moderate frontal and a severe parietal lobe hypoperfusion, especially on the left side. Macroscopic examination showed cortical atrophy, severe on the frontal, moderate on the parietal and mild on the posterior third temporal lobes, bilaterally. There was a slight atrophy on the neostriatum in the basal ganglia. The histopathological findings of the autopsy showed severe neuronal loss with intensive gemioscytic gliosis and variable degrees of status spongiosus in cortical layer. Hematoxylin-eosin and Bielschowsky staining did not show neuronal swelling (balooned cell), argyrophilic inclusion (Pick's bodies), neurofibrillary tangles nor senile plaques. Immunohistochemical staining for anti-ubiquitin, anti-tau, anti-beta-amyloide, and anti-prion protein were tested negative.",,"de Brito-Marques, P. R.;de Mello, R. V.;Montenegro, L.",2002,Jun,,0,
4764,Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes,"OBJECTIVE - Type 2 diabetes is associated with a moderate degree of cerebral atrophy and a higher white matter hyperintensity (WMH) volume. How these brain-imaging abnormalities evolve over time is unknown. The present study aims to quantify cerebral atrophy and WMH progression over 4 years in type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 55 patients with type 2 diabetes and 28 age-, sex-, and IQ-matched control participants had two 1.5T magnetic resonance imaging scans with a 4-year interval. Volumetric measurements of total brain, peripheral cerebrospinal fluid (CSF), lateral ventricles, and WMH were performed with k-nearest neighbor-based probabilistic segmentation. All volumes were expressed as percentage of intracranial volume. Linear regression analyses, adjusted for age and sex, were performed to compare brain volumes between the groups and to identify determinants of volumetric change within the type 2 diabetic group. RESULTS - At baseline, patients with type 2 diabetes had a significantly smaller total brain volume and larger peripheral CSF volume than control participants. In both groups, all volumes showed a significant change over time. Patients with type 2 diabetes had a greater increase in lateral ventricular volume than control participants (mean adjusted between-group difference in change over time [95% CI]: 0.11% in 4 years [0.00 to 0.22], P = 0.047). CONCLUSIONS - The greater increase in lateral ventricular volume over time in patients with type 2 diabetes compared with control participants shows that type 2 diabetes is associated with a slow increase of cerebral atrophy over the course of years. © 2010 by the American Diabetes Association.",,"De Bresser, J.;Tiehuis, A. M.;Van Den Berg, E.;Reijmer, Y. D.;Jongen, C.;Kappelle, L. J.;Mali, W. P.;Viergever, M. A.;Biessels, G. J.",2010,June,,0,
4765,Microvascular determinants of cognitive decline and brain volume change in elderly patients with type 2 diabetes,"Background/Aims: The present study examined the relationship between microvascular complications and cognitive decline and the development of structural brain abnormalities over a period of 4 years in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty-eight elderly patients with T2DM had 2 cognitive assessments with a 4-year interval. Two MRI scans, performed at the same time as the cognitive assessments, were available from 55 patients. Changes in cognitive performance over time were expressed as a regression-based index (RBI). Automated volumetric measurements of total brain, lateral ventricles and white matter hyperintensities were performed. The relationship between baseline microvascular complications [diabetic retinopathy, peripheral neuropathy or albuminuria (micro- or macroalbuminuria)] and cognition and brain volumes was examined with linear regression analyses adjusted for age and sex (for cognition also for IQ). Results: At baseline, diabetic retinopathy was present in 18% of patients, peripheral neuropathy in 36%, albuminuria in 15%. Retinopathy or neuropathy were not significantly associated with baseline cognition or brain volumes, or changes in these measures over time. Albuminuria was associated with a lower composite RBI score, indicating accelerated cognitive decline (adjusted mean difference between patients with or without albuminuria: -0.58, 95% CI -0.85 to -0.31, p < 0.001). Conclusion: Albuminuria predicted accelerated cognitive decline in patients with T2DM, but other microvascular complications were unrelated to accelerated cognitive decline or brain MRI abnormalities. © 2010 S. Karger AG, Basel.",glucose;hemoglobin A1c;insulin;adult;aged;albuminuria;article;brain size;brain ventricle;cognition;cognitive defect;diabetic patient;diabetic retinopathy;disease association;disease duration;elderly care;female;glucose blood level;glycemic control;human;insulin treatment;linear regression analysis;major clinical study;male;microalbuminuria;microvascularization;neuroimaging;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;peripheral neuropathy;priority journal;psychologic assessment;regression based index;scoring system;volumetry;white matter,"De Bresser, J.;Reijmer, Y. D.;Van Den Berg, E.;Breedijk, M. A.;Kappelle, L. J.;Viergever, M. A.;Biessels, G. J.",2010,,,0,
4766,[Cerebral Changes in the Morphometrics of HIV Patients] Cambios cerebrales en la morfometria en pacientes con VIH,"UNLABELLED: Cerebral atrophy is a common finding in patients infected with the Human Immunodeficiency Virus (HIV), particularly in patients with dementia. This disease shows neocortical compromise in late stages as well as compromise in the basal ganglia in early or asyntomatic phases. OBJECTIVE: Evaluate changes in total brain volume, caudate nucleus volume, nucleus accumbens volume, and fractional anisotropy of white matter tracts in HIV patients without neurodegenerative symptoms, in comparison with healthy subjects. METHODS: For segmentation and quantification purposes of the brain tissue, the brain and skull were extracted and the tissue was normalized according to total brain volume. From the tissue thus obtained, the caudate nucleus and nucleus accumbens volumes were segmented. The method of statistic spatial tractography was used for quantification and search of differences in the fractional anisotropy coefficient. RESULTS: The percentage of white matter volume with respect to brain volume was smaller in HIV patients (42.83+/-2.65 %) when compared with healthy subjects (43.56+/-1.60 %). The percentage of left nucleus accumbens volume in HIV patients was 0.0254+/-0.0073 % of the brain and 0.0351+/-0.0067 % in healthy subjects; (p<0.05). CONCLUSIONS: It was not evident A decrease in the volume of the gray matter parenchyma was not evident or significant, except in the left nucleus accumbens. Global but not regional changes were found in white matter tracts.",Brain morphometry;Hiv;Mri;Morfometria cerebral;Vih;anisotropia fraccional;fractional anisotropy;resonancia magnetica,"de Bedout, J. A.;Castrillon, J. G.;Rascovsky, S.;Garcia, L. M.;Velez, J. M.;Calvo, V. D.",2012,Sep,,0,
4767,[Cerebral Changes in the Morphometrics of HIV Patients],"Cerebral atrophy is a common finding in patients infected with the Human Immunodeficiency Virus (HIV), particularly in patients with dementia. This disease shows neocortical compromise in late stages as well as compromise in the basal ganglia in early or asyntomatic phases. OBJECTIVE: Evaluate changes in total brain volume, caudate nucleus volume, nucleus accumbens volume, and fractional anisotropy of white matter tracts in HIV patients without neurodegenerative symptoms, in comparison with healthy subjects. METHODS: For segmentation and quantification purposes of the brain tissue, the brain and skull were extracted and the tissue was normalized according to total brain volume. From the tissue thus obtained, the caudate nucleus and nucleus accumbens volumes were segmented. The method of statistic spatial tractography was used for quantification and search of differences in the fractional anisotropy coefficient. RESULTS: The percentage of white matter volume with respect to brain volume was smaller in HIV patients (42.83+/-2.65 %) when compared with healthy subjects (43.56+/-1.60 %). The percentage of left nucleus accumbens volume in HIV patients was 0.0254+/-0.0073 % of the brain and 0.0351+/-0.0067 % in healthy subjects; (p<0.05). CONCLUSIONS: It was not evident A decrease in the volume of the gray matter parenchyma was not evident or significant, except in the left nucleus accumbens. Global but not regional changes were found in white matter tracts.",Brain morphometry;Hiv;Mri;Morfometria cerebral;Vih;anisotropia fraccional;fractional anisotropy;resonancia magnetica,"de Bedout, J. A.;Castrillon, J. G.;Rascovsky, S.;Garcia, L. M.;Velez, J. M.;Calvo, V. D.",2012,Sep,10.1016/s0034-7450(14)60023-8,0,
4768,Fulminant inflammatory demyelination: long-term course and magnetic resonance imaging findings,"The course and prognosis of adult patients who recover from acute and extensive inflammatory demyelination, variously termed fulminant or Marburg's type of multiple sclerosis (MS), is poorly known. We report long-term magnetic resonance imaging (MRI) and neuropsychological findings in two patients who developed acute psychosis and a state resembling akinetic mutism, with CT scan evidence of extensive cerebral white matter damage. Both patients ultimately recovered, but were left with a severe, non-progressive dementia with prominent frontal lobe signs unassociated with motor impairment. Extensive residual MRI lesions with evidence of tissue destruction in the white matter and callosal atrophy were visible many years after the initial event One of the patients developed a single relapsing-remitting episode with multifocal neurological deficits several years after the onset, whereas the condition remained monophasic in the other patient during an 8 year follow-up. Our observations suggest that while patients with so-called ""fulminant"" demyelinating disorders may nowadays survive with supportive measures, the disorder may remain stabilized for many years following disease onset.",,"De Andres, C.;Dobato, J. L.;Mateo, D.;Benito, C.;Gimenez-Roldan, S.",1997,Mar,10.1111/j.1468-1331.1997.tb00322.x,0,
4769,Postmortem MRI: a novel window into the neurobiology of late life cognitive decline,"This study tested the hypothesis that indices of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late life decline in cognitive function and dementia, over and above contributions from common age-related neuropathologies. Cerebral hemispheres were obtained from 425 deceased older adults who had undergone 2 or more annual cognitive assessments, which included clinical diagnosis of dementia. Specimens underwent MRI to produce maps of transverse relaxation rate, R2. Voxelwise regression revealed brain regions where R2 was associated with cognitive decline. We then used random effects models to quantify the extent to which R2 accounted for variation in decline, after adjustment for demographics and neuropathologic indices of the 3 most common causes of dementia: Alzheimer's disease, cerebrovascular disease, and Lewy body disease. We additionally tested whether R2 was tied to greater likelihood of clinical diagnosis of Alzheimer's dementia using logistic regression models. During an average of 8.1 years, the mean rate of decline in global cognitive function was 0.13 unit per year (p < 0.0001). The tissue alteration most commonly related to decline was R2 slowing in white matter. Each unit decrease in R2 was associated with an additional 0.053-unit per year steepening of the rate of global cognitive decline (p < 0.001). Furthermore, R2 accounted for 8.4% of the variance in rate of global cognitive decline, above and beyond the 26.5% accounted for by demographics and neuropathologic indices, and 7.1%-11.2% of the variance of the decline rates in episodic, semantic, and working memory and perceptual speed. Alterations in R2 were also related to an increased odds of clinical diagnosis of Alzheimer's dementia (odds ratio = 2.000, 95% confidence interval 1.600, 2.604). Therefore, postmortem MRI indices of brain tissue integrity, particularly in white matter, are useful for elucidating the basis of late life cognitive impairment in older adults and complement traditional indices of neuropathology derived using histopathologic methods.",Alzheimer's disease;Postmortem MRI;Transverse relaxation;Voxelwise;White matter,"Dawe, R. J.;Yu, L.;Leurgans, S. E.;Schneider, J. A.;Buchman, A. S.;Arfanakis, K.;Bennett, D. A.;Boyle, P. A.",2016,Sep,10.1016/j.neurobiolaging.2016.05.023,0,
4770,Ex vivo T(2) relaxation: Associations with age-related neuropathology and cognition,"The transverse relaxation time constant, T(2), is sensitive to brain tissue's free water content and the presence of paramagnetic materials such as iron. In this study, exvivo magnetic resonance imaging was used to investigate alterations in T(2) related to Alzheimer's disease (AD) pathology and other types of neuropathology common in old age, as well as the relationship between T(2) alterations and cognition. Cerebral hemispheres were obtained from 371 deceased older adults. Using fast spin-echo imaging with multiple echo times, T(2) maps were produced and warped to a study-specific template. Hemispheres underwent neuropathologic examination for identification of AD pathology and other common age-related neuropathologies. Voxelwise linear regression was carried out to detect regions of pathology-related T(2) alterations and, in separate analyses, regions in which T(2) alterations were linked to antemortem cognitive performance. AD pathology was associated with T(2) prolongation in white matter of all lobes and T(2) shortening in the basal ganglia and insula. Gross infarcts were associated with T(2) prolongation in white matter of all lobes, and in the thalamus and basal ganglia. Hippocampal sclerosis was associated with T(2) prolongation in the hippocampus and white matter of the temporal lobe. After controlling for neuropathology, T(2) prolongation in the frontal lobe white matter was associated with lower performance in the episodic, semantic, and working memory domains. In addition, voxelwise analysis of invivo and exvivo T(2) values indicated a positive relationship between the two, though further investigation is necessary to accurately translate findings of the present study to the invivo case. © 2014 Elsevier Inc.",,"Dawe, R. J.;Bennett, D. A.;Schneider, J. A.;Leurgans, S. E.;Kotrotsou, A.;Boyle, P. A.;Arfanakis, K.",2014,July,,0,
4771,"Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study","The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6 x 10(-7)) or mild cognitive impairment (P = 9.6 x 10(-7)). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2 x 10(-7)). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Atrophy/ pathology/physiopathology;Autopsy;Cognition Disorders/pathology;Hippocampus/ pathology/physiopathology;Humans;Magnetic Resonance Imaging/ methods;Memory, Episodic;Mild Cognitive Impairment/pathology;Organ Size","Dawe, R. J.;Bennett, D. A.;Schneider, J. A.;Arfanakis, K.",2011,,10.1371/journal.pone.0026286,0,
4772,Cadasil - A new model of sub-cortical dementia,"We report 3 cases of Cadasil with dementia. In the 3 cases, the dementia had a subcortical and frontal presentation. It associated behavioural symptoms, amnesia, executive functions disturbances, bradyphrenia, slowing of information processing and frontal symptoms, without aphasia, apraxia or agnosia. One patient showed overt dementia before any focal neurological sign. Imaging of the brain was consistent with subcortical infarcts and leukoencephalopathy, without involvement of the cerebral cortex. We suggest that dementia and psychoaffective disturbances are major diagnostic criteria of Cadasil. This pathology is probably a good model for the neuropsychological study and the physiopathological analysis of the concept of subcortical dementia.",,"Davous, P.;Bequet, D.",1995,1995,,0,
4773,CADASIL: a review with proposed diagnostic criteria,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered as a new disease predominantly affecting the small vessels of the brain with an autosomal dominant transmission linked to chromosome 19. This review includes an historical perspective showing how the disease was identified from the spectrum of vascular leukoencephalopathies. More than two hundred patients have now been described, belonging to at least 30 unrelated pedigrees in Europe, America and Asia. The clinical features include four major neurological presentations associated in variable degrees during the course of the disease: migraine with or without aura, strokes or stroke-like episodes, major psychiatric symptoms and dementia. The patients are free of the classical vascular risk factors. The disease has a progressive or stepwise course with age at onset in the forties and a mean duration of 13.6 +/- 10.7 years. Death occurs in the fifties in a characteristic condition associating a pseudo-bulbar syndrome and subcortical dementia. Cerebral magnetic resonance imaging (MRI) is highly contributive to the diagnosis, showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter. Pathological data show macroscopic lesions similar to Binswanger's disease but different lesions of the small vessels including thickening of the media, characteristic PAS+ granular material and narrowing of the lumen. Skin biopsy may be a valuable diagnostic tool, showing ultrastructural alterations of skin vessels similar to those of brain vessels. The disease is highly homogeneous on a genetic basis and the identification of the gene Notch 3 on chromosome 19 has opened new avenues for research and genetic counselling. The pathogenesis of the disease has still to be elucidated. A definite diagnosis relies on genetical or pathological data. Diagnostic criteria are proposed to recognize the disease on clinical and imaging parameters. So far, no treatment has been reported to be successful for CADASIL. Copyright Lippincott-Raven Publishers",,"Davous, P.",1998,May,,0,
4774,The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part III. Reliability of a standardized MRI evaluation of Alzheimer's disease,"The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed procedures for standardized imaging and reporting of magnetic resonance (MR) findings in Alzheimer's disease (AD) for use by neuroradiologists in multiple medical centers using a variety of MR equipment and field strengths. After initial pretesting, we revised the protocol, expanded the summary rating scale to seven points, and added more illustrations. Fourteen participating neuroradiologists evaluated 28 MR scans of elderly patients, giving us the basis for judging interrater agreement. We obtained acceptable intraclass correlations (>0.79) for rating the size of the lateral and third ventricles and the temporal horn. Less satisfactory intraclass correlations occurred when rating other areas, including (1) global atrophy of the brain (0.70); (2) dilatation of the sulci of the temporal lobe (0.66); (3) frequency, location, and severity of white matter lesions (0.77); (4) sylvian fissure enlargement (0.70); and (5) cerebral sulcal dilatation (0.64). We also saw considerable variation in the reporting of cortical and lacunar infarcts. Despite careful design of the rating methodology and readings by experienced neuroradiologists, we did not find satisfactory interrater agreement for interpreting MR findings in elderly subjects. These findings may explain the difficulties encountered in applying similar subjective rating techniques that meet with success at one institution to multicenter studies. More objective and reproducible procedures are needed for interpretation of neuroimaging findings of AD in multicenter studies.",,"Davis, P. C.;Gray, L.;Albert, M.;Wilkinson, W.;Hughes, J.;Heyman, A.;Gado, M.;Kumar, A. J.;Destian, S.;Lee, C.;Duvall, E.;Kido, D.;Nelson, M. J.;Bello, J.;Weathers, S.;Jolesz, F.;Kikinis, R.;Brooks, M.",1992,1992,,0,
4775,An atypical presentation of Anton syndrome in a patient with preserved cognition despite multiple cerebral infarcts: A case report,,amlodipine;atorvastatin;glibenclamide;levothyroxine;rivastigmine;aged;amnesia;anton syndrome;behavior change;blindness;brain infarction;case report;clinical evaluation;clinical feature;cognition;diabetes mellitus;disease course;disease duration;disorientation;female;follow up;glaucoma;human;hypertension;hypothyroidism;medical history;memory disorder;mental health;multiinfarct dementia;neuropsychological test;note;nuclear magnetic resonance imaging;occipital lobe;paranoia;priority journal;sleep disorder;temporal lobe;visual disorder;visual hallucination,"Davis, G. P.;Sewell, R. A.;Levy, B.;Price, B. H.;Cunningham, M. G.",2009,,,0,
4776,Computer-mediated measurement and subjective ratings of white matter hyperintensities in vascular dementia: relationships to neuropsychological performance,"White matter hyperintensities (WMHs) are frequently found on MRI studies of vascular dementia (VaD) patients. As several studies have demonstrated that WMHs are often associated with severity of illness, cognitive impairment, and functional decline, the accurate and reliable measurement of WMHs on MRI is an important, yet often overlooked, prerequisite for accurate interpretation of neuroimaging studies. Using a sample of 39 VaD patients, we evaluated the reliability and validity of a visual ordinal rating scale and a computer-mediated thresholding technique to evaluate WMHs. Results indicated the computer-mediated technique had slightly stronger inter-rater reliability than the visual ordinal rating scale. Furthermore, the computer-mediated thresholding technique was correlated with measures of neuropsychological functioning believed to be compromised in VaD (i.e., psychomotor speed, executive functioning) while the visual rating scale was not. Results suggest that this computer-mediated thresholding technique is superior to visual ratings of WMHs.","Aged;Aged, 80 and over;Brain Mapping;Dementia, Vascular/pathology/*physiopathology;Female;Humans;Image Processing, Computer-Assisted/*methods;Learning/physiology;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Neuropsychological Tests/*statistics & numerical data;Problem Solving/physiology;Psychomotor Performance/physiology;Reproducibility of Results","Davis Garrett, K.;Cohen, R. A.;Paul, R. H.;Moser, D. J.;Malloy, P. F.;Shah, P.;Haque, O.",2004,Feb,10.1080/13854040490507154,0,
4777,White matter lesions: Prevalence and clinical phenotype in asymptomatic individuals aged ≥ 50 years,"Background: To assess the prevalence of early confluent/confluent white matter lesions (ec/cWMLs) in asymptomatic individuals aged ≥50 years and to identify associated clinical phenotypes. Methods: Cross-sectional analysis of 141 asymptomatic individuals aged ≥50 years assessed at an outpatient department in France. Brain magnetic resonance imaging was rated using the Fazekas scale. Age-adjusted odds ratios (ORs) and 95% confidence intervals were estimated using logistic models to investigate factors associated with ec/cWMLs; independent risk factors were identified by multivariate analysis. Results: Median age was 63 years; 53.9% were women, 32.6% had hypertension, and 76.6% had ≥1 cardiovascular risk factors. The prevalence of ec/cWMLs was 26.2%. Apart from age, independent risk factors were family history of cardiovascular event (OR = 5.55; 1.13-27.32) and hypertension (2.47; 1.05-5.81). Patients with ec/cWMLs had lower cognitive dual-task walking speed (1.15; 0.98-1.40), MMSE (1.41; 1.06-1.89), and FAB scores (5.21; 1.49-19.84). The Scheltens score was independently associated with the WML severity score. Conclusion: ec/cWMLs are common in asymptomatic community-dwelling individuals aged ≥50 years. They are associated with cardiovascular risk factors, impairments in global and executive cognitive function, and Scheltens score elevation.",adult;aged;Alzheimer disease;arterial stiffness;article;cardiovascular risk;cerebrovascular disease;clinical practice;cognition;community;female;human;hypertension;major clinical study;male;medial temporal lobe;Mini Mental State Examination;nuclear magnetic resonance imaging;outpatient department;phenotype;prevalence;priority journal;Stroop test;walking speed;white matter lesion,"David, J. P.;Ferrat, E.;Parisot, J.;Naga, H.;Lakroun, S.;Menasria, F.;Saddedine, S.;Natella, P. A.;Paillaud, E.;Fromentin, I.;Bastuji-Garin, S.",2016,,10.1159/000448991,0,
4778,"Prediction of MCI to AD conversion, via MRI, CSF biomarkers, and pattern classification","Magnetic resonance imaging (MRI) patterns were examined together with cerebrospinal fluid (CSF) biomarkers in serial scans of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI). The SPARE-AD score, summarizing brain atrophy patterns, was tested as a predictor of short-term conversion to Alzheimer's disease (AD). MCI individuals that converted to AD (MCI-C) had mostly positive baseline SPARE-AD (Spatial Pattern of Abnormalities for Recognition of Early AD) and atrophy in temporal lobe gray matter (GM) and white matter (WM), posterior cingulate/precuneous, and insula. MCI individuals that converted to AD had mostly AD-like baseline CSF biomarkers. MCI nonconverters (MCI-NC) had mixed baseline SPARE-AD and CSF values, suggesting that some MCI-NC subjects may later convert. Those MCI-NC with most negative baseline SPARE-AD scores (normal brain structure) had significantly higher baseline Mini Mental State Examination (MMSE) scores (28.67) than others, and relatively low annual rate of Mini Mental State Examination decrease (-0.25). MCI-NC with midlevel baseline SPARE-AD displayed faster annual rates of SPARE-AD increase (indicating progressing atrophy). SPARE-AD and CSF combination improved prediction over individual values. In summary, both SPARE-AD and CSF biomarkers showed high baseline sensitivity, however, many MCI-NC had abnormal baseline SPARE-AD and CSF biomarkers. Longer follow-up will elucidate the specificity of baseline measurements.","Aged;Aged, 80 and over;Alzheimer Disease/ cerebrospinal fluid/ classification/pathology;Biomarkers/cerebrospinal fluid;Disease Progression;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging/ trends;Male;Mild Cognitive Impairment/ cerebrospinal fluid/ classification/pathology;Neuropsychological Tests;Predictive Value of Tests","Davatzikos, C.;Bhatt, P.;Shaw, L. M.;Batmanghelich, K. N.;Trojanowski, J. Q.",2011,Dec,10.1016/j.neurobiolaging.2010.05.023,0,
4779,Registration based cortical thickness measurement,"Cortical thickness is an important biomarker for image-based studies of the brain. A diffeomorphic registration based cortical thickness (DiReCT) measure is introduced where a continuous one-to-one correspondence between the gray matter-white matter interface and the estimated gray matter-cerebrospinal fluid interface is given by a diffeomorphic mapping in the image space. Thickness is then defined in terms of a distance measure between the interfaces of this sheet like structure. This technique also provides a natural way to compute continuous estimates of thickness within buried sulci by preventing opposing gray matter banks from intersecting. In addition, the proposed method incorporates neuroanatomical constraints on thickness values as part of the mapping process. Evaluation of this method is presented on synthetic images. As an application to brain images, a longitudinal study of thickness change in frontotemporal dementia (FTD) spectrum disorder is reported.","Aged;Algorithms;Brain Mapping/ methods;Cerebral Cortex/ anatomy & histology;Dementia/ pathology;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Middle Aged","Das, S. R.;Avants, B. B.;Grossman, M.;Gee, J. C.",2009,Apr 15,10.1016/j.neuroimage.2008.12.016,0,
4780,Butyrylcholinesterase as a Diagnostic and Therapeutic Target for Alzheimer's Disease,"The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter acetylcholine. In the human brain BChE is mainly expressed in white matter and glia and in distinct populations of neurons in regions that are important in cognition and behavior, functions compromised in Alzheimer's disease (AD). AD is a neurodegenerative disorder causing dementia with no cure nor means for definitive diagnosis during life. In AD, BChE is found in association with pathology, such as beta-amyloid (Abeta) plaques, particularly in the cerebral cortex where BChE is not normally found in quantity. Up to 30% of cognitively normal older adults have abundant Abeta deposition in the brain. We have designed an imaging agent that can detect, through autoradiography, BChE-associated Abeta plaques in the cerebral cortex of AD brains, but does not visualize Abeta plaques in brains of cognitively normal individuals. Furthermore, in an AD mouse model with BChE gene knocked out, there are up to 70% fewer fibrillar Abeta brain plaques, suggesting diminished BChE activity could prove beneficial as a curative approach to AD. To that end, we have examined numerous N-10-carbonyl phenothiazines that are specific inhibitors of human BChE, revealing important details of the enzyme's active site gorge. These phenothiazines can be designed without potential side effects caused by neurotransmitter receptor interactions. In conclusion, BChE is potentially an important target for diagnosis and treatment of AD.",,"Darvesh, S.",2016,Apr 4,,0,
4781,"Relationship between cerebrospinal fluid flow, ventricles morphology, and DTI properties in internal capsules: differences between Alzheimer's disease and normal-pressure hydrocephalus","BACKGROUND: Normal-pressure hydrocephalus (NPH) and Alzheimer's disease (AD) have some similar clinical features and both involve white matter and cerebrospinal fluid (CSF) disorders. PURPOSE: To compare putative relationships between ventricular morphology, CSF flow, and white matter diffusion in AD and NPH. MATERIAL AND METHODS: Thirty patients (18 with AD and 12 with suspected NPH) were included in the study. All patients underwent a 3-Tesla MRI scan, which included phase-contrast MRI of the aqueduct (to assess the aqueductal CSF stroke volume) and a DTI session (to calculate the fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) in the internal capsules). RESULTS: FA was correlated with ventricular volume in the suspected NPH population (P < 0.001; rs = 0.88), whereas the ADC was highly correlated with the aqueductal CSF stroke volume in AD (P < 0.001; rs = 0.79). CONCLUSION: Although AD and NPH both involve CSF disorders, the two diseases do not have the same impact on the internal capsules. The magnitude of the ADC is related to the aqueductal CSF stroke volume in AD, whereas FA is related to ventricular volume in NPH.","Aged;Alzheimer Disease/ cerebrospinal fluid/ physiopathology;Anisotropy;Cerebral Ventricles/ physiopathology;Female;Humans;Hydrocephalus, Normal Pressure/ cerebrospinal fluid/ physiopathology;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/ methods;Male;Nerve Fibers, Myelinated/pathology;Prospective Studies","Daouk, J.;Chaarani, B.;Zmudka, J.;Capel, C.;Fichten, A.;Bouzerar, R.;Gondry-Jouet, C.;Jouanny, P.;Baledent, O.",2014,Oct,10.1177/0284185113508112,0,
4782,The effect of white matter lesions on cortical thickness and implications for cognitive function,"Background: Subcortical vascular cognitive impairment (VCI) is characterized by white matter lesions (WML); however, the relationship between WML and cognitive function remains equivocal. Recent cross-sectional evidence suggests that greater WML volume is associated with cortical thinning - a potential mediator for cognitive dysfunction. Thus, the purpose of this study was two-fold: 1) To investigate whether WML progression is independently associated with changes in cortical thickness; and 2) To assess the individual contribution of WML progression and changes in cortical thickness on cognitive function. Methods: This was a sub-analysis of a 2-arm randomized controlled trial assessing the effect of aerobic exercise on cognitive function in VCI. All measures were collected at baseline and at six months. Twenty-nine participants consented to complete an MRI scan to quantify WMLs and cortical thickness. Cognitive function was measured by: 1) Digit symbol substitution test (DSST), 2) Verbal Digits Span, and 3) Stroop Test. A multiple linear regression assessed: 1) the independent contribution WML progression on cortical thinning; and 2) the independent contribution of change in WML and cortical thickness on cognitive function - all analyses controlled for age and group allocation. Results: Regression analyses controlling for age and group allocation indicated that increased WMLs was independently associated with cortical thinning over time - R-square change of 10.2%, Sig F Change = 0.013. Additionally, increased cortical thinning was associated with greater impairments of the DSST over 6 months - R-Square Change = 4.6%, Sig F Chang = 0.008. Change in WMLs was not independently associated with cognitive function - Sig F Change >0.05. Conclusions: Our findings suggest that WML progression contribute to cortical thinning and this in turn is associated with reduced cognitive performance as measured by the DSST. This points to the importance of secondary prevention as reduced WML progression could benefit cognitive function and delay the onset of dementia in people with VCI.",cognition;Canadian;cerebrovascular accident;white matter lesion;human;cognitive defect;digit symbol substitution test;randomized controlled trial;aerobic exercise;multiple linear regression analysis;arm;Stroop test;dementia;secondary prevention;regression analysis;nuclear magnetic resonance imaging,"Dao, E.;Hsu, L.;Chiu, B.;Hsiung, R. G.",2015,,,0,
4783,"Various mental behavioral disorders in Parkinson's disease, primary degenerative senile dementia, and multiple infarction dementia","Following 2-4 years of hospitalization, the mental and physical ability of 21 patients with typical idiopathic PD, 10 patients with atypical Parkinson's syndrome and signs of cerebral arteriosclerosis, 29 patients with MID. and 14 patients with senile dementia of the Alzheimer type were evaluated according to various rating scales. All idiopathic parkinsonian patients had suffered from the disease for over 8 years. All patients were over 70 years of age and continuously subjected to the same environment. EEG and CT was performed. A rating scale consisting of 18 items for evaluation of the mental and physical capacity and ability to cope with daily psychosocial demands was used for each patient. Statistically highly significant differences resulted between the relative good mental ability of patients with idiopathic Parkinson's syndrome, with the exception of some brief pharmacotoxic psychoses, and the lower rating scores of patients with senile dementia of Alzheimer type and multiple infarction dementia. A smaller subgroup of patients with Parkinson's syndrome and additional focal signs in the neurological status and EEG showed moderate mental functional loss and a more frequent incidence of pharmacotoxic psychoses than the patients with idiopathic PD. Just as few congruencies of mental ability were found between patients with idiopathic, typical PD and patients with senile dementia of the Alzheimer type as between idiopathic PD and MID. Permanent dementia is not characteristic of patients with typical idiopathic PD even in advanced age. It is, however, for patients with MID and SDAT.","Aged;Alzheimer Disease/psychology;Atrophy;Cerebral Cortex/pathology;Cerebral Infarction/*psychology;Dementia/*psychology;Electroencephalography;Humans;Hydrocephalus/psychology;Intracranial Arteriosclerosis/psychology;Neurocognitive Disorders/*psychology;Parkinson Disease/*psychology;Social Adjustment;Tomography, X-Ray Computed","Danielczyk, W.",1983,,,0,
4784,White matter tract integrity in aging and Alzheimer's disease,"The pattern of degenerative changes in the brain white matter (WM) in aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) has been under debate. Methods of image analysis are an important factor affecting the outcomes of various studies. Here we used diffusion tensor imaging (DTI) to obtain fractional anisotropy (FA) measures of the WM in healthy young (n = 8), healthy elderly (n = 22), MCI (n = 8), and AD patients (n = 16). We then applied ""tract-based spatial statistics"" (TBSS) to study the effects of aging, MCI, and AD on WM integrity. Our results show that changes in WM integrity (that is, decreases in FA) are different between healthy aging and AD: in healthy older subjects compared with healthy young subjects decreased FA was primarily observed in frontal, parietal, and subcortical areas whereas in AD, compared with healthy older subjects, decreased FA was only observed in the left anterior temporal lobe. This different pattern of decreased anatomical connectivity in normal aging and AD suggests that AD is not merely accelerated aging.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Anisotropy;Attention/physiology;Brain/ pathology;Brain Mapping;Cognition Disorders/pathology;Diffusion Magnetic Resonance Imaging/methods;Female;Humans;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests;Problem Solving/physiology;Statistics as Topic;Young Adult","Damoiseaux, J. S.;Smith, S. M.;Witter, M. P.;Sanz-Arigita, E. J.;Barkhof, F.;Scheltens, P.;Stam, C. J.;Zarei, M.;Rombouts, S. A.",2009,Apr,10.1002/hbm.20563,0,
4785,White matter lesions and cognitive deficits: Relevance of lesion pattern?,"Magnetic resonance imaging (MRI) permits efficient visualization of white matter lesions (WML). A growing body of literature deals with the correlation of WML and cognitive dysfunction with conflicting results. We studied the influence of lesion pattern as well as size by analyzing MRI and psychometric test performance in 2 patient collectives with different WML patterns. 22 patients with myotonic dystrophy (MD) and mainly subcortical WML were compared with 39 patients with multiple sclerosis (MS) and mainly periventricular lesions. 73% of MD patients had WML, the extent of which correlated with cognitive deficits. Severely impaired patients had psychometric findings compatible with 'subcortical' dementia. In MS the extent of WML alone did not correlate significantly with cognitive deficits. Significant cognitive dysfunction was observed with extension of WML to areas of white matter immediately underlying cortex, but not with exclusively periventricular lesions. Cerebral atrophy had less impact. Comparison of MD and MS indicates that WML immediately subjacent to cortex are likely to cause significant cognitive deficits, whereas extensive periventricular demyelination may cause no major dysfunction. This may relate to early disturbance of associative fibers by subcortical lesions. Our results emphasize the significance of pattern as well as total extent of WML. Myotonic dystrophy is a useful model to study the effect of subcortical lesions, due to a typical lesion pattern unusual in other conditions.",,"Damian, M. S.;Schilling, G.;Bachmann, G.;Simon, C.;Stoppler, S.;Dorndorf, W.",1994,1994,,0,
4786,Magnetic resonance imaging of muscle and brain in myotonic dystrophy,"Myotonic dystrophy (MD) is characterized by myotonia, weakness and extramuscular symptoms, including intellectual impairment. We performed magnetic resonance imaging (MRI) of brain and muscle in 25 MD patients: 81% had cerebral atrophy (severe in 36%); 68% had focal white matter lesions, which were large and multiple in 27%. Brain MRI findings correlated with mental impairment; the severity of both correlated with disease duration. Changes in brain and muscle MRI were progressive with time, but independent of each other. Muscle MRI findings were fatty degeneration and loss of bulk. In the calves, the medial gastrocnemius muscles were involved earliest and the posterior tibial muscles relatively spared. In the thighs the vastus muscles were damaged most often and the rectus femoris least. Focal muscle damage was efficiently visualized, sometimes preceding clinical detection. Muscle MRI was less sensitive than conventional methods for early diagnosis, but ideal for follow-up, owing to its non-invasiveness and examiner-independence.",,"Damian, M. S.;Bachmann, G.;Herrmann, D.;Dorndorf, W.",1993,1993,,0,
4787,Multispectral MRI segmentation of age related white matter changes using a cascade of support vector machines,"White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm. © 2012 Elsevier B.V.",,"Damangir, S.;Manzouri, A.;Oppedal, K.;Carlsson, S.;Firbank, M. J.;Sonnesyn, H.;Tysnes, O. B.;O'Brien, J. T.;Beyer, M. K.;Westman, E.;Aarsland, D.;Wahlund, L. O.;Spulber, G.",2012,15,,0,
4788,Decline in total cerebral blood flow is linked with increase in periventricular but not deep white matter hyperintensities,"PURPOSE: To retrospectively investigate the association between changes in total cerebral blood flow and progression of total, periventricular, and deep white matter hyperintensities over time. MATERIALS AND METHODS: The institutional ethics review board approved the protocol for the prospective magnetic resonance (MR) imaging study, and all participants gave written informed consent. Participants also agreed to future retrospective analysis of their MR data for research purposes. In this substudy of the Prospective Study of Pravastatin in the Elderly at Risk, investigators performed a repeated MR imaging examination after an average interval of 33 months (standard deviation, 1.4) in 390 elderly men and women (ages 70-82 years at baseline) without dementia who were at high vascular risk. White matter hyperintensities were quantified with a semiautomatic method, and total cerebral blood flow was measured with a gradient-echo phase-contrast MR imaging technique. The association between total cerebral blood flow and volume of white matter hyperintensities was analyzed with logistic regression. RESULTS: There was no association between baseline cerebral blood flow and prevalence of total, periventricular, or deep white matter hyperintensities at baseline MR imaging. Moreover, decline in cerebral blood flow was not associated with increase in total load of white matter hyperintensities. When the total volume of white matter hyperintensities was separated into periventricular and deep hyperintensities, for every 50 mL/min decrease in total cerebral blood flow there was a 1.32 (95% confidence interval: 1.06, 1.66; P = .015) increase in risk for developing periventricular white matter hyperintensities; there was no association, however, between decrease in total cerebral blood flow and risk of developing deep white matter hyperintensities (odds ratio, 1.00 [95% confidence interval: 0.79, 1.25]; P = .98). CONCLUSION: Decline in total cerebral blood flow is associated with increase in volume of periventricular but not deep white matter hyperintensities.","Aging [pathology] [physiology];Brain [pathology];Cerebrovascular Circulation [physiology];Follow-Up Studies;Logistic Models;Magnetic Resonance Imaging;Retrospective Studies;Risk Factors;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Sr-stroke","Dam, V. H.;Heuvel, D. M.;Craen, A. J.;Bollen, E. L.;Murray, H. M.;Westendorp, R. G.;Blauw, G. J.;Buchem, M. A.",2007,,10.1148/radiol.2431052111,0,
4789,Radiological-Pathological Correlation in Alzheimer's Disease: Systematic Review of Antemortem Magnetic Resonance Imaging Findings,"BACKGROUND: The standard method of ascertaining Alzheimer's disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these etiologies and provide a diagnosis in vivo. OBJECTIVE: We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD. METHODS: We explored PubMed in June-July 2015 using ""Alzheimer's disease"" and combinations of radiological and pathological terms. After exclusion following screening and full-text assessment of the 552 extracted manuscripts, three others were added from their reference list. In the end, we report results based on 27 articles. RESULTS: Independently of normal age-related brain atrophy, AD pathology is associated with whole-brain and hippocampal atrophy and ventricular expansion as observed on T1-weighted images. Moreover, cerebral amyloid angiopathy and cortical microinfarcts are also related to brain volume loss in AD. Hippocampal sclerosis and TDP-43 are associated with hippocampal and medial temporal lobe atrophy, respectively. Brain volume loss correlates more strongly with tangles than with any other pathological finding. White matter hyperintensities observed on proton density, T2-weighted and FLAIR images are strongly related to vascular pathologies, but are also associated with other histological changes such as gliosis or demyelination. CONCLUSION: Cerebral atrophy and white matter changes in the living brain reflect underlying neuropathology and may be detectable using antemortem MRI. In vivo MRI may therefore be an avenue for AD pathological staging.",Alzheimer's disease;antemortem diagnosis;dementia;magnetic resonance imaging;neuroimaging;neuropathology,"Dallaire-Theroux, C.;Callahan, B. L.;Potvin, O.;Saikali, S.;Duchesne, S.",2017,,,0,
4790,White matter hyperintensities do not impact cognitive function in patients with newly diagnosed Parkinson's disease,"The objective of this study was to investigate total volume and spatial distribution of white matter hyperintensities (WMH) in a large sample of newly diagnosed Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI) compared to normal controls (NC). Furthermore, we aimed to examine the impact of the WMH on attention-executive performance in PD. MCI is regarded as a pre-dementia stage. Studies on MCI have found WMH associated with reduced cognitive function, especially in the attention and executive domains. The present study included 163 incident, drug-naive PD patients (66.2+/-9.1 years and disease duration 27.1+/-19.8 months) and 102 age-matched NC (65.7+/-9.4 years). Thirty (30) subjects in the PD sample presented MCI, whereas 133 did not. MCI was classified based on tests for memory, attention-executive and visuospatial function compared to the NC group, taking age, sex and education into consideration. WMH were outlined on FLAIR scans using a semi-automated technique. Total WMH volumes were compared between the 3 study groups, and spatial distribution of normalized WMH masks in each group were compared using voxel-wise probability maps. Regression analysis examined the possible impact of WMH on attention-executive scores in the PD group. Analysis showed that there were no significant differences between the 3 groups in total volume or spatial distribution of WMH. In addition there was no significant relationship between total volume or spatial distribution of WMH and attention-executive functions in PD. We conclude that in this PD cohort, cognitive impairment seems to be independent of WMH damage.","Aged;Brain/*pathology;*Cognition;Cognition Disorders/*etiology/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Parkinson Disease/*complications/*pathology","Dalaker, T. O.;Larsen, J. P.;Dwyer, M. G.;Aarsland, D.;Beyer, M. K.;Alves, G.;Bronnick, K.;Tysnes, O. B.;Zivadinov, R.",2009,Oct 1,10.1016/j.neuroimage.2009.06.020,0,
4791,Disrupted rich club network in behavioral variant frontotemporal dementia and early-onset Alzheimer's disease,"In network analysis, the so-called ""rich club"" describes the core areas of the brain that are more densely interconnected among themselves than expected by chance, and has been identified as a fundamental aspect of the human brain connectome. This is the first in-depth diffusion imaging study to investigate the rich club along with other organizational changes in the brain's anatomical network in behavioral frontotemporal dementia (bvFTD), and a matched cohort with early-onset Alzheimer's disease (EOAD). Our study sheds light on how bvFTD and EOAD affect connectivity of white matter fiber pathways in the brain, revealing differences and commonalities in the connectome among the dementias. To analyze the breakdown in connectivity, we studied three groups: 20 bvFTD, 23 EOAD, and 37 healthy elderly controls. All participants were scanned with diffusion-weighted magnetic resonance imaging (MRI), and based on whole-brain probabilistic tractography and cortical parcellations, we analyzed the rich club of the brain's connectivity network. This revealed distinct patterns of disruption in both forms of dementia. In the connectome, we detected less disruption overall in EOAD than in bvFTD [false discovery rate (FDR) critical Pperm = 5.7 x 10(-3) , 10,000 permutations], with more involvement of richly interconnected areas of the brain (chi-squared P = 1.4 x 10(-4) )-predominantly posterior cognitive alterations. In bvFTD, we found a greater spread of disruption including the rich club (FDR critical Pperm = 6 x 10(-4) ), but especially more peripheral alterations (chi-squared P = 6.5 x 10(-3) ), particularly in medial frontal areas of the brain, in line with the known behavioral socioemotional deficits seen in these patients. Hum Brain Mapp 37:868-883, 2016. (c) 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.",,"Daianu, M.;Mezher, A.;Mendez, M. F.;Jahanshad, N.;Jimenez, E. E.;Thompson, P. M.",2016,Mar,10.1002/hbm.23069,0,
4792,An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease,"Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.","Age of Onset;Alzheimer Disease/ diagnostic imaging;Brain/ diagnostic imaging;Cohort Studies;Diffusion Magnetic Resonance Imaging;Diffusion Tensor Imaging;Female;Frontotemporal Dementia/ diagnostic imaging;Humans;Imaging, Three-Dimensional;Male;Mental Status Schedule;Middle Aged;White Matter/ diagnostic imaging;Behavioral variant frontotemporal dementia;Diffusion tensor imaging (DTI);Early-onset Alzheimer's disease;Tract analysis;White matter","Daianu, M.;Mendez, M. F.;Baboyan, V. G.;Jin, Y.;Melrose, R. J.;Jimenez, E. E.;Thompson, P. M.",2016,Dec,,0,4793
4793,An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease,"Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.",,"Daianu, M.;Mendez, M. F.;Baboyan, V. G.;Jin, Y.;Melrose, R. J.;Jimenez, E. E.;Thompson, P. M.",2015,Oct 29,10.1007/s11682-015-9458-5,0,
4794,Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network,"Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative–50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the “rich club” – a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length, and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline. Hum Brain Mapp 36:3087–3103, 2015. © 2015 Wiley Periodicals, Inc.",aged;Alzheimer disease;article;brain cortex;brain size;connectome;controlled study;diffusion weighted imaging;female;human;longitudinal study;major clinical study;male;mild cognitive impairment;nerve cell network;neuroimaging;nuclear magnetic resonance scanner;priority journal;rich club network;tractography,"Daianu, M.;Jahanshad, N.;Nir, T. M.;Jack, C. R.;Weiner, M. W.;Bernstein, M. A.;Thompson, P. M.",2015,,10.1002/hbm.22830,0,
4795,Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network,"Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative-50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the ""rich club"" - a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length, and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline.",,"Daianu, M.;Jahanshad, N.;Nir, T. M.;Jack, C. R.;Weiner, M. W.;Bernstein, M. A.;Thompson, P. M.",2015,,,0,4794
4796,Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease,"Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla whole-brain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the ""high-cost"" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.",,"Daianu, M.;Jahanshad, N.;Mendez, M. F.;Bartzokis, G.;Jimenez, E. E.;Thompson, P. M.",2015,Mar 20,10.1117/12.2082352,0,
4797,Alzheimer's Disease Disrupts Rich Club Organization in Brain Connectivity Networks,"Diffusion imaging and brain connectivity analyses can monitor white matter deterioration, revealing how neural pathways break down in aging and Alzheimer's disease (AD). Here we tested how AD disrupts the 'rich club' effect - a network property found in the normal brain - where high-degree nodes in the connectivity network are more heavily interconnected with each other than expected by chance. We analyzed 3-Tesla whole-brain diffusionweighted images (DWI) from 66 subjects (22 AD/44 normal elderly). We performed whole-brain tractography based on the orientation distribution functions. Connectivity matrices were compiled, representing the proportion of detected fibers interconnecting 68 cortical regions. As expected, AD patients had a lower nodal degree (average number of connections) in cortical regions implicated in the disease. Unexpectedly, the normalized rich club coefficient was higher in AD. AD disrupts cortical networks by removing connections; when these networks are thresholded, organizational properties are disrupted leading to additional new biomarkers of AD.",,"Daianu, M.;Dennis, E. L.;Jahanshad, N.;Nir, T. M.;Toga, A. W.;Jack, C. R., Jr.;Weiner, M. W.;Thompson, P. M.",2013,,10.1109/isbi.2013.6556463,0,
4798,Abnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension,"BACKGROUND AND PURPOSE: The purpose of this study was to examine regional cerebral blood flow (rCBF) in normal cognitive-performing subjects with hypertension (HTN) using continuous arterial spin-labeled MRI. The most common explanation for the effect of blood pressure on cognition is that HTN increases the risk of cerebrovascular disease, and it may increase the risk for Alzheimer disease possibly through small vessel disease, ischemia, oxidative stress, and inflammation. However, few studies to date have examined the rCBF of cognitively normal subjects with HTN in population-based cohorts, and none have used continuous arterial spin-labeled MRI. This is a noninvasive technique that does not require either injections or ionizing radiation and can measure absolute rCBF rates over the entire brain. METHODS: rCBF was measured at 1.5 T using continuous arterial spin-labeled MRI in 41 cognitively normal subjects who were participating in the Cardiovascular Health Study Cognition Study. A deformable atrophy-corrected registration method was used to warp the rCBF maps to the standard colin27 brain space. Image and cluster-based statistical analyses were performed between subject groups. RESULTS: Cognitively normal subjects with HTN (n=19) had decreased rCBF in the putamen, globus pallidus, bilaterally, and in the left hippocampus compared with normotensives (n=22). In addition, decreased rCBF was observed in the right and left anterior cingulate gyrus with extension to the subcallosal region, left posterior cingulate gyrus and medial precuneus, left lateral inferior and superior frontal, and inferior parietal, left orbitofrontal, and left superior temporal cortices. CONCLUSIONS: rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.","Aged;Aged, 80 and over;Cerebral Cortex/blood supply;Cerebrovascular Circulation;Cognition/ physiology;Cognition Disorders/ diagnosis/physiopathology;Female;Globus Pallidus/blood supply;Gyrus Cinguli/blood supply;Humans;Hypertension/ physiopathology;Magnetic Resonance Imaging;Male;Putamen/blood supply;Spin Labels","Dai, W.;Lopez, O. L.;Carmichael, O. T.;Becker, J. T.;Kuller, L. H.;Gach, H. M.",2008,Feb,10.1161/strokeaha.107.495457,0,
4799,Susceptibility artefact correction using dynamic graph cuts: Application to neurosurgery,"Echo Planar Imaging (EPI) is routinely used in diffusion and functional MR imaging due to its rapid acquisition time. However, the long readout period makes it prone to susceptibility artefacts which results in geometric and intensity distortions of the acquired image. The use of these distorted images for neuronavigation hampers the effectiveness of image-guided surgery systems as critical white matter tracts and functionally eloquent brain areas cannot be accurately localised. In this paper, we present a novel method for correction of distortions arising from susceptibility artefacts in EPI images. The proposed method combines fieldmap and image registration based correction techniques in a unified framework. A phase unwrapping algorithm is presented that can efficiently compute the B(0) magnetic field inhomogeneity map as well as the uncertainty associated with the estimated solution through the use of dynamic graph cuts. This information is fed to a subsequent image registration step to further refine the results in areas with high uncertainty. This work has been integrated into the surgical workflow at the National Hospital for Neurology and Neurosurgery and its effectiveness in correcting for geometric distortions due to susceptibility artefacts is demonstrated on EPI images acquired with an interventional MRI scanner during neurosurgery. © 2014 The Authors.",,"Daga, P.;Pendse, T.;Modat, M.;White, M.;Mancini, L.;Winston, G. P.;McEvoy, A. W.;Thornton, J.;Yousry, T.;Drobnjak, I.;Duncan, J. S.;Ourselin, S.",2014,October,,0,
4800,Validation of a Regression Technique for Segmentation of White Matter Hyperintensities in Alzheimer's Disease,"Segmentation and volumetric quantification of white matter hyperintensities (WMHs) is essential in assessment and monitoring of the vascular burden in aging and Alzheimer's disease (AD), especially when considering their effect on cognition. Manually segmenting WMHs in large cohorts is technically unfeasible due to time and accuracy concerns. Automated tools that can detect WMHs robustly and with high accuracy are needed. Here, we present and validate a fully automatic technique for segmentation and volumetric quantification of WMHs in aging and AD. The proposed technique combines intensity and location features frommultiplemagnetic resonance imaging contrasts and manually labeled training data with a linear classifier to perform fast and robust segmentations. It provides both a continuous subject specific WMH map reflecting different levels of tissue damage and binary segmentations. Themethodwas used to detectWMHs in 80 elderly/AD brains (ADC data set) as well as 40 healthy subjects at risk of AD (PREVENT-AD data set). Robustness across different scanners was validated using ten subjects from ADNI2/GO study. Voxel-wise and volumetric agreements were evaluated using Dice similarity index (SI) and intra-class correlation (ICC), yielding ICC=0.96 , SI = 0.62+/-0.16 for ADC data set and ICC=0.78 , SI=0.51+/-0.15 for PREVENT-AD data set. The proposed method was robust in the independent sample yielding SI=0.64+/-0.17 with ICC=0.93 for ADNI2/GO subjects. The proposed method provides fast, accurate, and robust segmentations on previously unseen data from different models of scanners, making it ideal to study WMHs in large scale multi-site studies.",Alzheimer Disease;Humans;Magnetic Resonance Imaging;Regression Analysis;White Matter,"Dadar, M.;Pascoal, T. A.;Manitsirikul, S.;Misquitta, K.;Fonov, V. S.;Tartaglia, M. C.;Breitner, J.;Rosa-Neto, P.;Carmichael, O. T.;Decarli, C.;Collins, D. L.",2017,Aug,,0,
4801,Performance comparison of 10 different classification techniques in segmenting white matter hyperintensities in aging,"INTRODUCTION: White matter hyperintensities (WMHs) are areas of abnormal signal on magnetic resonance images (MRIs) that characterize various types of histopathological lesions. The load and location of WMHs are important clinical measures that may indicate the presence of small vessel disease in aging and Alzheimer's disease (AD) patients. Manually segmenting WMHs is time consuming and prone to inter-rater and intra-rater variabilities. Automated tools that can accurately and robustly detect these lesions can be used to measure the vascular burden in individuals with AD or the elderly population in general. Many WMH segmentation techniques use a classifier in combination with a set of intensity and location features to segment WMHs, however, the optimal choice of classifier is unknown. METHODS: We compare 10 different linear and nonlinear classification techniques to identify WMHs from MRI data. Each classifier is trained and optimized based on a set of features obtained from co-registered MR images containing spatial location and intensity information. We further assess the performance of the classifiers using different combinations of MRI contrast information. The performances of the different classifiers were compared on three heterogeneous multi-site datasets, including images acquired with different scanners and different scan-parameters. These included data from the ADC study from University of California Davis, the NACC database and the ADNI study. The classifiers (naive Bayes, logistic regression, decision trees, random forests, support vector machines, k-nearest neighbors, bagging, and boosting) were evaluated using a variety of voxel-wise and volumetric similarity measures such as Dice Kappa similarity index (SI), Intra-Class Correlation (ICC), and sensitivity as well as computational burden and processing times. These investigations enable meaningful comparisons between the performances of different classifiers to determine the most suitable classifiers for segmentation of WMHs. In the spirit of open-source science, we also make available a fully automated tool for segmentation of WMHs with pre-trained classifiers for all these techniques. RESULTS: Random Forests yielded the best performance among all classifiers with mean Dice Kappa (SI) of 0.66+/-0.17 and ICC=0.99 for the ADC dataset (using T1w, T2w, PD, and FLAIR scans), SI=0.72+/-0.10, ICC=0.93 for the NACC dataset (using T1w and FLAIR scans), SI=0.66+/-0.23, ICC=0.94 for ADNI1 dataset (using T1w, T2w, and PD scans) and SI=0.72+/-0.19, ICC=0.96 for ADNI2/GO dataset (using T1w and FLAIR scans). Not using the T2w/PD information did not change the performance of the Random Forest classifier (SI=0.66+/-0.17, ICC=0.99). However, not using FLAIR information in the ADC dataset significantly decreased the Dice Kappa, but the volumetric correlation did not drastically change (SI=0.47+/-0.21, ICC=0.95). CONCLUSION: Our investigations showed that with appropriate features, most off-the-shelf classifiers are able to accurately detect WMHs in presence of FLAIR scan information, while Random Forests had the best performance across all datasets. However, we observed that the performances of most linear classifiers and some nonlinear classifiers drastically decline in absence of FLAIR information, with Random Forest still retaining the best performance.",Alzheimer's disease;Classification;Segmentation;White matter hyperintensities,"Dadar, M.;Maranzano, J.;Misquitta, K.;Anor, C. J.;Fonov, V. S.;Tartaglia, M. C.;Carmichael, O. T.;Decarli, C.;Collins, D. L.;Alzheimer's Disease Neuroimaging, Initiative",2017,Aug 15,,0,
4802,Validation of T1w-based segmentations of white matter hyperintensity volumes in large-scale datasets of aging,"INTRODUCTION: Fluid-attenuated Inversion Recovery (FLAIR) and dual T2w and proton density (PD) magnetic resonance images (MRIs) are considered to be the optimum sequences for detecting white matter hyperintensities (WMHs) in aging and Alzheimer's disease populations. However, many existing large multisite studies forgo their acquisition in favor of other MRI sequences due to economic and time constraints. METHODS: In this article, we have investigated whether FLAIR and T2w/PD sequences are necessary to detect WMHs in Alzheimer's and aging studies, compared to using only T1w images. Using a previously validated automated tool based on a Random Forests classifier, WMHs were segmented for the baseline visits of subjects from ADC, ADNI1, and ADNI2/GO studies with and without T2w/PD and FLAIR information. The obtained WMH loads (WMHLs) in different lobes were then correlated with manually segmented WMHLs, each other, age, cognitive, and clinical measures to assess the strength of the correlations with and without using T2w/PD and FLAIR information. RESULTS: The WMHLs obtained from T1w-Only segmentations correlated with the manual WMHLs (ADNI1: r = .743, p < .001, ADNI2/GO: r = .904, p < .001), segmentations obtained from T1w + T2w + PD for ADNI1 (r = .888, p < .001) and T1w + FLAIR for ADNI2/GO (r = .969, p < .001), age (ADNI1: r = .391, p < .001, ADNI2/GO: r = .466, p < .001), and ADAS13 (ADNI1: r = .227, p < .001, ADNI2/GO: r = .190, p < 0.001), and NPI (ADNI1: r = .290, p < .001, ADNI2/GO: r = 0.144, p < .001), controlling for age. CONCLUSION: Our results suggest that while T2w/PD and FLAIR provide more accurate estimates of the true WMHLs, T1w-Only segmentations can still provide estimates that hold strong correlations with the actual WMHLs, age, and performance on various cognitive/clinical scales, giving added value to datasets where T2w/PD or FLAIR are not available.",Azheimer's disease;T1w hypointensities;cerebrovascular disease;cognitive impairment;small vessel disease;white matter integrity,"Dadar, M.;Maranzano, J.;Ducharme, S.;Carmichael, O. T.;Decarli, C.;Collins, D. L.;Alzheimer's Disease Neuroimaging, Initiative",2018,Mar,,0,
4803,Analysis of related risk factors of neurological deterioration in patients with acute cerebral infarction,"Objective To investigate the related risk factors of neurological deterioration ( ND) in patients with acute cerebral infarction. Methods A total of 446 patients with acute cerebral infarction admitted to the Department of Neurology, Zhongda Hospital, Southeast University from January 2012 to December 2013 were analyzed retrospectively. ND was defined as the reevaluation of the National Institutes of Health Stroke Scale ( NIHSS) scores at any time for the increased admission baseline score 2 ( ND2) or 4 ( ND4) within the first 72 hours. All subjects were divided into a ND2 group ( n = 107) and a non-ND2 group ( n = 339) or a ND4 group ( n = 62 ) and a non-ND4 group (n = 384). The differences of general demography, vascular risk factors, imaging, and hematological data among the different groups were compared. Results Of the 446 patients, 107 cases (24. 0% ) were diagnosed as ND2 and 62 cases (13. 9% ) were diagnosed as ND4. The result of univariate analysis showed that there were significant differences in the length of hospital stav, age, baseline NIHSS score, baseline systolic blood pressure on admission, guilty artery occlusion, and the levels of leukocyte,fasting glucose, and C-reaetive protein between the ND2 patients and the non-ND2 patients ( all P < 0. 05 ) . There were significant differences in sex, age , atrial fibrillation , baseline NIHSS score, baseline systolic blood pressure on admission, guilty artery occlusion, and the level of C-reactive protein between the NEW patients and the non-ND4 patients (all P <0. 05). After adjustment for the confounding factors, the results of Logistic regression analysis showed that the baseline NIHSS score (OR, 1. 114, 95% CI 1.0481 -1. 185, P =0.001) , C-reactive protein ( OR, 1. 014,95% CI 1. 004-1. 024 ,P = 0. 004) , and guilty artery occlusion ( OR,2. 303 ,95% CI 1. 152-4. 606 ,P = 0. 018) were independently correlated with ND2; while the age ( OR, 1. 040,95 % CI 1. 011 -1. 070, P = 0. 006 ) , systolic blood pressure ( OR, 1. 015,95% CI 1. 003 -1. 027 , P = 0. 018) , C-reaetive protein ( OR, 1. 016,95% CI 1. 005 -1. 026, P = 0.003),and guilty artery occlusion ( OR,2. 845 ,95% CI 1.291 -2. 269, P = 0. 009) were independently correlated with ND4. Conclusion The early onset of ND in patients with acute cerebral infarction are closely associated with age, stroke severity, baseline systolic blood pressure, C-reactive protein, and occlusion of guilty artery. In the clinical diagnosis and treatment,detecting the above indicators timely may contribute to identify the patients with acute cerebral infarction and early progressive deterioration.",,"Da, Z.;Zhai, Z. P.;Yan, F. L.",2014,1,,0,
4804,CADASIL: case report,"Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebral arteriopathy caused by mutations in the Notch-3 gene. The diagnosis is reached by skin biopsy revealing presence of granular osmiophilic material (GOM), and/or by genetic testing for Notch-3. We report a case of a 52-year-old man with recurrent transient ischemic attacks (TIA), migraine, in addition to progressive sensory, motor and cognitive impairment. He was submitted to a neuropsychological assessment with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery along with other tests, as well as neuroimaging and genetic analysis for Notch-3, confirming the diagnosis. Executive function, memory, language and important apraxic changes were found. Imaging studies suggested greater involvement in the frontal lobes and deep areas of the brain.",Cadasil;Notch3;cognition;neuropsychology,"da Silva, J. C. V.;Gasparetto, E. L.;Engelhardt, E.",2012,Jul-Sep,,0,
4805,Cognitive and neuroimaging profile of a Brazilian family with Cadasil,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease leading to small infarcts and subcortical vascular dementia. This study presents results from the neuropsychological and neuroimaging evaluation of functionally autonomous individuals of a Brazilian family with CADASIL. The causal mutation was confirmed in four family members. Seven individuals from two generations were evaluated using the CERAD battery and additional neuropsychological tests and were submitted (6 individuals) to magnetic resonance imaging (MRI) of the brain with specific protocols for white matter lesion quantification. Apraxic changes and fast progression over nine months (neuropsychological reevaluation of 6 individuals) were found in many individuals. The MRI study suggests greater involvement of frontal lobes in more severely affected individuals. Even functionally independent individuals may exhibit significant neuropsychological and neuroimaging changes. Apraxia, little commented on in literature, and rapidly progressive cognitive changes were found in this group.",,"da Silva, J. C. V.;Gasparetto, E. L.;André, C.",2011,June,,0,
4806,White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration,"The objective of the current study was to quantify the degree of white matter (WM) abnormalities in chronic and virally suppressed HIV-infected (HIV+) persons while carefully taking into account demographic and disease factors. Diffusion tensor imaging (DTI) was conducted in 40 HIV− and 82 HIV+ men with comparable demographics and life style factors. The HIV+ sample was clinically stable with successful viral control. Diffusion was measured across 32 non-colinear directions with a b-value of 1000 s/mm2; fractional anisotropy (FA) and mean diffusivity (MD) maps were quantified with Itrack IDL. Using the ENIGMA DTI protocol, FA and MD values were extracted for each participant and in 11 skeleton regions of interest (SROI) from standard labels in the JHU ICBM-81 atlas covering major striato-frontal and parietal tracks. We found no major differences in FA and MD values across the 11 SROI between study groups. Within the HIV+ sample, we found that a higher CNS penetrating antiretroviral treatment, higher current CD4+ T cell count, and immune recovery from the nadir CD4+ T cell count were associated with increased FA and decreased MD (p < 0.05–0.006), while HIV duration, symptomatic, and asymptomatic cognitive impairment were associated with decreased FA and increased MD (p < 0.01–0.004). Stability of HIV treatment and antiretroviral CNS penetration efficiency in addition to current and historical immune recovery were related to higher FA and lower MD (p = 0.04–p < 0.01). In conclusion, WM DTI measures are near normal except for patients with neurocognitive impairment and longer HIV disease duration.",CD4+ T lymphocyte;cell count;cognitive defect;congenital malformation;diffusion tensor imaging;disease course;fractional anisotropy;HIV associated dementia;human;lifestyle;major clinical study;male;microcatheter;normal human;quantitative study;skeleton;white matter;endogenous compound;intermediate density lipoprotein,"Cysique, L. A.;Soares, J. R.;Geng, G.;Scarpetta, M.;Moffat, K.;Green, M.;Brew, B. J.;Henry, R. G.;Rae, C.",2017,,10.1007/s13365-017-0524-1,0,
4807,"HIV, Vascular and Aging Injuries in the Brain of Clinically Stable HIV-Infected Adults: A 1H MRS Study","Background:Cardiovascular disease (CVD) and premature aging have been hypothesized as new risk factors for HIV associated neurocognitive disorders (HAND) in adults with virally-suppressed HIV infection. Moreover, their significance and relation to more classical HAND biomarkers remain unclear.Methods:92 HIV- infected (HIV+) adults stable on combined antiretroviral therapy (cART) and 30 age-comparable HIV-negative (HIV-) subjects underwent 1H Magnetic Resonance Spectroscopy (MRS) of the frontal white matter (targeting HIV, normal aging or CVD-related neurochemical injury), caudate nucleus (targeting HIV neurochemical injury), and posterior cingulate cortex (targeting normal/pathological aging, CVD-related neurochemical changes). All also underwent standard neuropsychological (NP) testing. CVD risk scores were calculated. HIV disease biomarkers were collected and cerebrospinal fluid (CSF) neuroinflammation biomarkers were obtained in 38 HIV+ individuals.Results:Relative to HIV- individuals, HIV+ individuals presented mild MRS alterations: in the frontal white matter: lower N-Acetyl-Aspartate (NAA) (p<.04) and higher myo-inositol (mIo) (p<.04); in the caudate: lower NAA (p =. 01); and in the posterior cingulate cortex: higher mIo (p<.008- also significant when Holm-Sidak corrected) and higher Choline/NAA (p<.04). Regression models showed that an HIV*age interaction was associated with lower frontal white matter NAA. CVD risk factors were associated with lower posterior cingulate cortex and caudate NAA in both groups. Past acute CVD events in the HIV+ group were associated with increased mIo in the posterior cingulate cortex. HIV duration was associated with lower caudate NAA; greater CNS cART penetration was associated with lower mIo in the posterior cingulate cortex and the degree of immune recovery on cART was associated with higher NAA in the frontal white matter. CSF neopterin was associated with higher mIo in the posterior cingulate cortex and frontal white matter.Conclusions:In chronically HIV+ adults with long-term viral suppression, current CVD risk, past CVD and age are independent factors for neuronal injury and inflammation. This suggests a tripartite model of HIV, CVD and age likely driven by chronic inflammation. © 2013 Cysique et al.",beta 2 microglobulin;biological marker;choline;inositol;n acetylaspartic acid;neopterin;adult;age;aged;aging;article;brain radiography;brain region;cardiovascular disease;cardiovascular risk;caudate nucleus;CD4+ T lymphocyte;cerebrospinal fluid analysis;controlled study;disease duration;highly active antiretroviral therapy;HIV associated dementia;human;Human immunodeficiency virus infection;immunoreactivity;major clinical study;male;metabolite;nervous system inflammation;neuropsychological test;posterior cingulate;proton nuclear magnetic resonance;scoring system;white matter,"Cysique, L. A.;Moffat, K.;Moore, D. M.;Lane, T. A.;Davies, N. W. S.;Carr, A.;Brew, B. J.;Rae, C.",2013,,,0,
4808,Corpus callosum size may predict late-life depression in women: a 10-year follow-up study,"BACKGROUND: Recent research on late-life depression (LLD) pathophysiology suggests the implication of abnormalities in cerebral white matter and particularly in interhemispheric transfer. Corpus callosum (CC) is the main brain interhemispheric commissure. Hence, we investigated the association between baseline CC measures and risk of LDD. METHODS: We studied 467 non-demented individuals without LLD at baseline from a cohort of elderly community-dwelling people (the ESPRIT study). LLD was assessed at year 2, 4, 7 and 10 of the study follow-up. At baseline, T1-weighted magnetic resonance images were manually traced to measure the mid-sagittal areas of the anterior, mid and posterior CC. Multivariate Cox proportional hazards models stratified by sex were used to predict LLD incidence over 10 years. RESULTS: A significant interaction between gender and CC size was found (p=0.02). LLD incidence in elderly women, but not in men, was significantly associated with smaller anterior (HR 1.37 [1.05-1.79] p=0.017), mid (HR 1.43 [1.09-1.86] p=0.008), posterior (HR 1.39 [1.12-1.74] p=0.002) and total (HR 1.53 [1.16-2.00] p=0.002) CC areas at baseline in Cox models adjusted for age, education, global cognitive impairment, ischemic pathologies, left-handedness, white matter lesion, intracranial volume and past depression. LIMITATIONS: The main limitation was the retrospective assessment of major depression. CONCLUSION: Smaller CC size is a predictive factor of incident LLD over 10 years in elderly women independently of cognitive deterioration. Our finding suggests a possible role of CC and reduced interhemispheric connectivity in LLD pathophysiology. Extensive explorations are needed to clarify the mechanisms leading to CC morphometric changes in mood disorders.","Aged;Aged, 80 and over;Corpus Callosum/ anatomy & histology;Depressive Disorder/ epidemiology;Female;Follow-Up Studies;Humans;Reproducibility of Results;Retrospective Studies;Risk Factors","Cyprien, F.;Courtet, P.;Poulain, V.;Maller, J.;Meslin, C.;Bonafe, A.;Le Bars, E.;Ancelin, M. L.;Ritchie, K.;Artero, S.",2014,Aug,10.1016/j.jad.2014.04.040,0,
4809,Protocol for a randomized controlled trial evaluating the effect of physical activity on delaying the progression of white matter changes on MRI in older adults with memory complaints and mild cognitive impairment: the AIBL Active trial,"BACKGROUND: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI). METHODS/DESIGN: This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures. DISCUSSION: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000612910.",Adult;Aged;Brain/ pathology/physiopathology;Cognitive Therapy/methods;Disease Progression;Exercise Therapy/ methods/standards;Female;Geriatric Assessment;Humans;Magnetic Resonance Imaging/instrumentation/ methods;Male;Memory Disorders/pathology/physiopathology/therapy;Middle Aged;Mild Cognitive Impairment/physiopathology/prevention & control/therapy;Single-Blind Method;Treatment Outcome,"Cyarto, E. V.;Lautenschlager, N. T.;Desmond, P. M.;Ames, D.;Szoeke, C.;Salvado, O.;Sharman, M. J.;Ellis, K. A.;Phal, P. M.;Masters, C. L.;Rowe, C. C.;Martins, R. N.;Cox, K. L.",2012,,10.1186/1471-244x-12-167,0,
4810,Aibl active: A randomized controlled trial of physical activity to delay the progression of white matter hyperintensities on mri in older adults at risk of cognitive decline,"Background: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. More recently, cerebrovascular disease (CVD) risk factors, including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with CVD risk factors, memory complaints and cognitive impairment. The AIBL Active study is designed to investigate whether a 24-month physical activity program can slow down the progression of WMH on magnetic resonance imaging (MRI). Methods: This 24-month randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging. Participants must have SMC with or without MCI and at least one cerebrovascular risk factor. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study - FABS). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, biomarkers and PET Florbetapir comprise secondary measures. Results: The PA intervention successfully used in FABS was extended from a 6-month program to a 24-month program. This paper offers an overview of the trial design, the PA intervention, as well as strategies used to retain participants in the study. Conclusions: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's pathologies.",randomized controlled trial;human;physical activity;white matter;adult;risk;risk factor;memory;dementia;aging;fitness;nuclear magnetic resonance imaging;cognitive defect;hypercholesterolemia;smoking;heart disease;hypertension;drug therapy;quality of life;mild cognitive impairment;brain;cerebrovascular disease;lifestyle;imaging;cognition;arm;study design;pathology,"Cyarto, E.;Cox, K.;Desmond, P.;Ames, D.;Szoeke, C.;Salvado, O.;Sharman, M.;Ellis, K.;Phal, P.;Masters, C.;Rowe, C.;Martins, R.;Lautenschlager, N.",2012,,10.1016/j.jalz.2012.05.1377,0,
4811,Dementia in multiple sclerosis: Report of a case with cortical gray matter involvement and frontotemporal-like clinical features,"Multiple sclerosis (MS) is primarily a white matter disease, but may also involve the gray matter, a feature not often demonstrated in vivo. This report presents the case of a patient with MS and clinical features mimicking frontotemporal dementia due to clear-cut cortical gray matter involvement in the left frontal lobe. © 2012 Elsevier Ireland Ltd.",baclofen;beta1a interferon;diazepam;memantine;mianserin;olanzapine;adult;agitation;aphasia;article;attention deficit disorder;case report;clinical feature;dementia;demyelination;depersonalization;dysarthria;eating disorder;female;frontal lobe;frontotemporal dementia;gliosis;gray matter;human;insomnia;multiple sclerosis;nuclear magnetic resonance imaging;nystagmus;priority journal;urine incontinence;white matter,"Curral, R.;Correia, R.;Lopes, R.;Maia, D.;Rio, E.;Bastos-Leite, A. J.",2012,,,0,
4812,The relationship between late onset bipolar affective disorder which responds na valproate and hypertension: A case report,"Bipolar affective disorders beginning after the age 50 are named late onset bipolar disorder. It is indicated that the etiology of late onset bipolar disorders can be primary or secondary to another factor. Therapeutic agents, infections, metabolic instability, brain tumors and aneurysm, epilepsy, toxins, traumatic brain injury, hyperthyroidism, multiple sclerosis, Cushing syndrome, dementia and cerebrovascular diseases are known as some of these etiologic factors. In this report a 55 year old women, who has been hypertension diagnosis for 3 years is observed. White matter hyperintensity has been seen in her MRI and she has had late onset bipolar affective disorder diagnose. In the light of literature the etiology of late onset bipolar affective disorder will be discussed in this report.",valproic acid;adult;article;bipolar disorder;case report;clinical feature;diagnostic imaging;drug response;female;human;hypertension;image analysis;neuroimaging;onset age;symptom,"Cumurcu, B. E.;Karlidaǧ, R.;Özdemir, S.;Gül, I. G.;Öztoprak, E.",2012,,,0,
4813,Dilation of Virchow-Robin spaces in CADASIL,"To precise the severity of dilated Virchow-Robin spaces (VRS) in CADASIL patients and to determine their correlation with clinical presentation and other abnormalities on cerebral Magnetic Resonance Imaging (MRI). Dilated VRS were previously associated with aging, hypertension, dementia, epilepsy or migraine. We already reported increased frequency of enlarged VRS in CADASIL patients when compared with family members without the affected haplotype. We analysed clinical and MRI data from 50 CADASIL patients collected prospectively in our center. The presence of dilated VRS was assessed in the subcortical white matter of temporal lobes, the centrum semi-ovale and the basal ganglia. Their severity in each region was evaluated according to the scale proposed by Heier. We compared the clinical data, the severity of white matter abnormalities and the presence of microbleeds in patients with and without dilated VRS. Seventy-eight percent of patients in our series had dilated VRS, mostly located in the lentiform nuclei (94%) and subcortical white matter of the temporal lobes (66%). The severity of these lesions was variable but not correlated neither to the extent of white matter abnormalities nor to the clinical presentation in our patients. Only the age was found to be related to the extent of dilated VRS. Dilated VRS are frequent in CADASIL and mostly located in the temporal white matter and basal ganglia. The dilation of perivascular spaces does not seem to be directly related to the occurrence of ischemic or hemorrhagic lesions in CADASIL. In contrast, the relation with age suggests that either aging, progression of vascular wall alterations during the course of the disease, or both of these processes can favour the extension of VRS in CADASIL. © 2006 EFNS.",,"Cumurciuc, R.;Guichard, J. P.;Reizine, D.;Gray, F.;Bousser, M. G.;Chabriat, H.",2006,February,,0,
4814,Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus;peak-48,-18,-14; Z E = 5.65, p FWE corr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r =-0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population.",adult;article;CADASIL;clinical article;cognition;connectome;executive function;female;functional magnetic resonance imaging;human;longitudinal study;male;middle temporal gyrus;priority journal;resting state network;scoring system,"Cullen, B.;Moreton, F. C.;Stringer, M. S.;Krishnadas, R.;Kalladka, D.;López-González, M. R.;Santosh, C.;Schwarzbauer, C.;Muir, K. W.",2015,,,0,
4815,Automated detection of amnestic mild cognitive impairment in community-dwelling elderly adults: A combined spatial atrophy and white matter alteration approach,"Amnestic mild cognitive impairment (aMCI) is a syndrome widely considered to be prodromal Alzheimer's disease. Accurate diagnosis of aMCI would enable earlier treatment, and could thus help minimize the prevalence of Alzheimer's disease. The aim of the present study was to evaluate a magnetic resonance imaging-based automated classification schema for identifying aMCI. This was carried out in a sample of community-dwelling adults aged 70-90. years old: 79 with a clinical diagnosis of aMCI and 204 who were cognitively normal. Our schema was novel in using measures of both spatial atrophy, derived from T1-weighted images, and white matter alterations, assessed with diffusion tensor imaging (DTI) tract-based spatial statistics (TBSS). Subcortical volumetric features were extracted using a FreeSurfer-initialized Large Deformation Diffeomorphic Metric Mapping (FS. +. LDDMM) segmentation approach, and fractional anisotropy (FA) values obtained for white matter regions of interest. Features were ranked by their ability to discriminate between aMCI and normal cognition, and a support vector machine (SVM) selected an optimal feature subset that was used to train SVM classifiers. As evaluated via 10-fold cross-validation, the classification performance characteristics achieved by our schema were: accuracy, 71.09%; sensitivity, 51.96%; specificity, 78.40%; and area under the curve, 0.7003. Additionally, we identified numerous socio-demographic, lifestyle, health and other factors potentially implicated in the misclassification of individuals by our schema and those previously used by others. Given its high level of performance, our classification schema could facilitate the early detection of aMCI in community-dwelling elderly adults. © 2011 Elsevier Inc.",,"Cui, Y.;Wen, W.;Lipnicki, D. M.;Beg, M. F.;Jin, J. S.;Luo, S.;Zhu, W.;Kochan, N. A.;Reppermund, S.;Zhuang, L.;Raamana, P. R.;Liu, T.;Trollor, J. N.;Wang, L.;Brodaty, H.;Sachdev, P. S.",2012,16,,0,
4816,Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease,"Background: Single-nucleotide polymorphisms (SNPs) in 2 distinct regions of the gene for the sortilin-related receptor (SORL1) (bounded by consecutively numbered SNPs 8-10 and 22-25) were shown to be associated with Alzheimer disease (AD) in multiple ethnically diverse samples. Objective: To test the hypothesis that SORL1 is associated with brain magnetic resonance imaging (MRI) measurements of atrophy and/or vascular disease. Design, Setting, and Patients: We evaluated the association of 30 SNPs spanning SORL1 with MRI measures of general cerebral atrophy, hippocampal atrophy, white matter hyperintensities, and overall cerebrovascular disease in 44 African American and 182 white sibships from the MIRAGE Study. We performed single-and 3-SNP haplotype association analyses using family-based tests. Haplotypes found to be significantly associated with at least 1 MRI trait were tested for association with 6 pathological traits in a separate sample of 69 white patients with autopsy-confirmed AD. Results: In white patients, white matter hyperintensities were associated with multiple markers in the region encompassing SNPs 6 to 10, whereas cerebral and hippocampal atrophy were associated with markers from the region including SNPs 21 to 26. Examination of specific 3-SNP haplotypes from these 2 regions in the autopsy-confirmed cases of AD revealed association of white matter disease with SNPs 8 to 10 and association of hippocampal atrophy with SNPs 22 to 26. The haplotype CGC at SNPs 8 to 10 was associated with fewer white matter changes in the clinical (P <.001) and autopsy (P=.02) samples. Conclusions: Variants of SORL1 previously associated with AD are also associated with MRI and neuropathological measures of neurodegenerative and cerebrovascular disease. These findings not only support the hypothesis that multiple areas in SORL1 are of functional importance but also raise the possibility that multiple SORL1 variants influence amyloid precursor protein or endothelial lipoprotein processing or both in different regions of the brain. © 2008 American Medical Association.",,"Cuenco, K. T.;Lunetta, K. L.;Baldwin, C. T.;McKee, A. C.;Guo, J.;Cupples, L. A.;Green, R. C.;St. George-Hyslop, P. H.;Chui, H.;DeCarli, C.;Farrer, L. A.",2008,December,,0,
4817,Magnetic resonance imaging traits in siblings discordant for Alzheimer disease,"BACKGROUND: Magnetic resonance imaging (MRI) can aid clinical assessment of brain changes potentially correlated with Alzheimer disease (AD). MRI traits may improve our ability to identify genes associated with AD-outcomes. We evaluated semi-quantitative MRI measures as endophenotypes for genetic studies by assessing their association with AD in families from the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) Study. METHODS: Discordant siblings from multiple ethnicities were ascertained through a single affected proband. Semi-quantitative MRI measures were obtained for each individual. The association between continuous/ordinal MRI traits and AD were analyzed using generalized estimating equations. Medical history and Apolipoprotein E (APOE)epsilon4 status were evaluated as potential confounders. RESULTS: Comparisons of 214 affected and 234 unaffected subjects from 229 sibships revealed that general cerebral atrophy, white matter hyperintensities (WMH), and mediotemporal atrophy differed significantly between groups (each at P < .0001) and varied by ethnicity. Age at MRI and duration of AD confounded all associations between AD and MRI traits. Among unaffected sibs, the presence of at least one APOEepsilon4 allele and MRI infarction was associated with more WMH after adjusting for age at MRI. CONCLUSION: The strong association between MRI traits and AD suggests that MRI traits may be informative endophenotypes for basic and clinical studies of AD. In particular, WMH may be a marker of vascular disease that contributes to AD pathogenesis.","Aged;Alzheimer Disease/diagnosis/ethnology/genetics/ pathology;Apolipoprotein E4/genetics;Atrophy;Confounding Factors (Epidemiology);Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Phenotype;Regression Analysis;Risk Factors;Siblings;Statistics, Nonparametric","Cuenco, K. T.;Green, R. C.;Zhang, J.;Lunetta, K.;Erlich, P. M.;Cupples, L. A.;Farrer, L. A.;DeCarli, C.",2008,Jul,10.1111/j.1552-6569.2007.00191.x,0,
4818,A progressive multifocal neurological syndrome in a 42-year-old woman,"This is the case of a 42-year-old female who presented with transient dizziness. Her symptoms and signs progressed to include dysarthria, ataxia and cognitive decline over 2 years, such that she was unable to care for herself. She died 4 years after first presentation without a diagnosis. Investigations revealed a normochromic normocytic anaemia. Cerebrospinal fluid was normal. Serial computed tomography brain showed a wedge-shaped frontal infarct but no progressive changes. Examination at autopsy showed discoloration of the gray and white matter of the brain and spinal cord. Microscopy of leptomeningeal and parenchymal vessels showed they were filled with atypical B lymphocytes confined to the intravascular space with multiple infarcts in the brain, cerebellum and spinal cord. A diagnosis of intravascular B cell lymphoma was made and is discussed. © 2011 International Society of Neuropathology.",adult;aneurysm clip;article;autopsy;brain artery aneurysm;case report;clinical feature;cognitive defect;computer assisted tomography;Creutzfeldt Jakob disease;dementia;differential diagnosis;disease course;dizziness;female;human;human tissue;immunohistochemistry;neurologic disease;paraneoplastic syndrome;Shy Drager syndrome;spinocerebellar degeneration,"Cryan, J.;Brett, F. M.",2011,,,0,
4819,On the white matter changes in spongiform encephalopathy,"Two males and 2 females aged between 37 and 78 years clinically diagnosed as suffering from Creutzfeld-Jakob disease (CJD) were studied. The evolution of the disease from onset of symptoms to death varied between 2 and 48 months. CT scan on admission showed a slight diffuse cortical atrophy in 2 cases. Repeat CT scans showed progressive cortical atrophy in 4 cases, while in 2 cases mild to moderate diffuse hypodense white matter lesions were seen. Neuropathological findings demonstrated classical histological changes of CJD in the gray matter. The white matter showed diffuse demyelination and areas of focal pallor except for the internal capsule, which was spared in all cases. Histologically the white matter changes consisted of spongiform changes with proliferation of hypertrophic astrocytes and depletion of oligodendrocytes with myelin loss. Immunohistological staining for myelin basic protein showed granular degeneration in areas of diffuse demyelination and in discrete foci. Focal lesions with granulae of degenerated myelin, not appreciable in luxol fast blue stain, were also found with the myelin basic protein antibody. On the basis of our findings and those of others, we suggest that our cases are examples of a spongiform panencephalopathy in which host peculiarities may allow involvement of white matter to occur.",adult;aged;article;brain atrophy;brain spongiosis;case report;computer assisted tomography;Creutzfeldt Jakob disease;demyelination;female;human;human tissue;immunohistology;male;white matter,"Cruz-Sanchez, F. F.;Ferrer, I.;Rossi, M. L.",1991,,,0,
4820,"Clinical pathologic case report: A 70-year-old man with inflammatory cerebral amyloid angiopathy causing headache, cognitive impairment, and aphasia","A 70-year-old man presented with two months of worsening cognitive impairment, hallucinations, and difficulty speaking, with superimposed headaches. Cerebrospinal fluid analysis was notable for lymphocytic pleocytosis and elevated protein. Imaging studies revealed multiple acute and subacute infarcts with cortical microhemorrhages. The patient underwent a stereotactic brain biopsy. In this article, we discuss the patient's differential diagnosis, pathologic findings, ultimate diagnosis, and clinical outcome.",Caa;Cerebral amyloid angiopathy;Dementia;Inflammatory CAA;iCAA,"Crotty, G. F.;McKee, K.;Saadi, A.;Young, A. C.;Solomon, I. H.;Lyons, J. L.",2018,Mar,,0,
4821,Loss of olfactory tract integrity affects cortical metabolism in the brain and olfactory regions in aging and mild cognitive impairment,"Olfactory dysfunction is an early feature of Alzheimer disease. This study used multimodal imaging of PET and (18)F-FDG combined with diffusion tensor imaging (DTI) to investigate the association of fiber tract integrity in the olfactory tract with cortical glucose metabolism in subjects with mild cognitive impairment (MCI) and normal controls. We hypothesized that MCI subjects would show loss of olfactory tract integrity and may have altered associations with glucose metabolism. METHODS: Subjects diagnosed with amnestic MCI (n = 12) and normal controls (n = 23) received standard brain (18)F-FDG PET and DTI with 32 gradient directions on a 3-T MR imaging scanner. Fractional anisotropy (FA) maps were generated. Voxelwise correlation analysis of olfactory tract FA values with (18)F-FDG PET images was performed. RESULTS: Integrated analysis over all subjects indicated a positive correlation between white matter integrity in the olfactory tract and metabolic activity in olfactory processing structures, including the rostral prefrontal cortex, dorsomedial thalamus, hypothalamus, orbitofrontal cortex, and uncus, and in the superior temporal gyrus, insula, and anterior cingulate cortex. Subjects with MCI, compared with normal controls, showed differential associations of olfactory tract integrity with medial temporal lobe and posterior cortical structures. CONCLUSION: These findings indicate that impairment of axonal integrity or neuronal loss may be linked to functional metabolic changes and that disease-specific neurodegeneration may affect this relationship. Multimodal imaging using (18)F-FDG PET and DTI may provide better insights into aging and neurodegenerative processes.",Aged;Aging/ metabolism/ pathology;Anisotropy;Axons/metabolism/pathology;Case-Control Studies;Fluorodeoxyglucose F18;Glucose/metabolism;Humans;Male;Middle Aged;Mild Cognitive Impairment/ metabolism/ pathology/radionuclide imaging;Nerve Net/metabolism/pathology/radionuclide imaging;Olfactory Pathways/ metabolism/ pathology/radionuclide imaging;Positron-Emission Tomography,"Cross, D. J.;Anzai, Y.;Petrie, E. C.;Martin, N.;Richards, T. L.;Maravilla, K. R.;Peskind, E. R.;Minoshima, S.",2013,Aug,10.2967/jnumed.112.116558,0,
4822,Intravascular malignant lymphomatosis,"Neoplastic angioendotheliosis is a rare, severe, disease characterized by neoplastic proliferation of mononuclear cells within the lumen of small blood vessels. The clinical signs are usually dermatological and neurological. We report the case of a 57 year old woman who died after 20 months of subacute dementia. She had had also transient recurrent episodes of right paresthesiae and paresis. CSF proteins were increased MRI showed areas of high signal in the white matter. Post-mortem showed widespread ischemic lesions, mainly in the subcortical white matter. Microscopically there was marked proliferation of cells in most CNS blood vessels. Similar cells were present in adrenals, liver, uterus, lungs and kidneys. Immunohistochemical studies showed intensive staining for leukocyte common antigen and negative staining for factor VIII-related antigen, a specific endothelial cell marker.",adult;article;autopsy;case report;female;giant cell;histology;human;lymphoma;priority journal,"Croisile, B.;Tommasi, M.;Jouvet, A.;Truffert, A.;Trillet, M.;Aimard, G.",1990,,,0,
4823,Low levels of high density lipoprotein increase the severity of cerebral white matter changes: implications for prevention and treatment of cerebrovascular diseases,"BACKGROUND AND PURPOSE: Cerebral White matter changes (WMC) are a frequent finding on CT and MRI scans of elderly individuals, particularly in those with vascular risk factors, cerberovascular disease, and cognitive impairment. METHODS: 56 subjects were included in the study after the review of reports of more than 200 consecutive brain Computerized Tomography (CT) and magnetic resonance imaging (MRI) examinations from the out-patient and in-patient units of the Department of Geriatric Medicine at Karolinska University Hospital, Huddinge during 2001-2002. MRI was performed using a 1.5 T system and WMC lesions were graded 1-3 using a visual scale. Total-cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG) levels were determined using enzymatic techniques after 12 hours overnight fasting. Apo E genotyping was performed as described. RESULTS: Low HDL levels were associated with higher severity of WMC on MRI (p=0.002). Subjects with the Apo E4 allele had higher LDL (p=0.02) and apoB levels (p=0.005). The presence of the Apo E4 allele was higher in the group of subjects with severe WMC (grade 3). However, there was no statistically significant group difference in severity of WMC lesions between carriers and non-carriers of Apo E4 allele. CONCLUSIONS: Low HDL is strongly associated with adverse coronary and cerebrovascular outcomes. Our results indicate that low HDL levels are also associated with more severe WMC lesions on MRI. Dietary or medical adjustment of HDL levels could have important implications for treatment and prevention of cerebral WMC, cerebrovascular and neurodegenerative diseases such as stroke and dementia.","Aged;Aged, 80 and over;Analysis of Variance;Apolipoproteins E/genetics;Brain/ pathology/radiography;Brain Mapping;Cerebrovascular Disorders/genetics/ pathology/radiography;Female;Humans;Lipoproteins, HDL/ metabolism;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Nerve Fibers, Myelinated/ metabolism;Neuropsychological Tests;Retrospective Studies;Severity of Illness Index;Sex Factors;Tomography, X-Ray Computed/methods","Crisby, M.;Bronge, L.;Wahlund, L. O.",2010,Sep,,0,
4824,Multimodal MRI quantification of the common neurostructural bases within the FTD-ALS continuum,"The continuum hypothesis linking the behavioral variant of frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) is supported by clinical, pathological, genetic, and neuroimaging evidence. In the present multimodal magnetic resonance study, we characterized the site and extent of shared neurostructural changes in gray and white matter in 20 bvFTD and 19 ALS patients without dementia. We found an overlap of macrostructural and microstructural damage in both patient groups compared with healthy controls, involving the right orbital and the bilateral anterior cingulate cortices, the corticospinal tract and corpus callosum. The quantification of gray and white matter damage within the areas of shared alterations highlighted a higher degree of atrophy in orbitofrontal and frontomedial regions in patients with more severe executive and/or behavioral symptoms, and a higher degree of degeneration in the motor pathway in patients with more severe motor neuron disorders. Our finding provides additional evidence confirming the FTD-ALS continuum hypothesis and supports the notion of a bimodal but convergent pattern of neurostructural changes characterizing bvFTD and ALS.",ALS-FTD continuum hypothesis;Amyotrophic lateral sclerosis;Behavioral variant of frontotemporal dementia;Corticospinal tract;Tract-based spatial statistics;Voxel-based morphometry,"Crespi, C.;Dodich, A.;Cappa, S. F.;Canessa, N.;Iannaccone, S.;Corbo, M.;Lunetta, C.;Falini, A.;Cerami, C.",2018,Feb,,0,
4825,Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis,"Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia.",,"Crespi, C.;Cerami, C.;Dodich, A.;Canessa, N.;Iannaccone, S.;Corbo, M.;Lunetta, C.;Falini, A.;Cappa, S. F.",2016,,10.1371/journal.pone.0161034,0,
4826,Microstructural white matter correlates of emotion recognition impairment in Amyotrophic Lateral Sclerosis,"Amyotrophic Lateral Sclerosis (ALS) is associated in about half of the cases with behavioral and cognitive disorders, including impairments in socio-emotional processing, considered as key-features for the diagnosis of the behavioral variant of frontotemporal dementia (bv-FTD). The neurostructural bases of emotional deficits in ALS, however, still remain largely unexplored. Here we aim to assess emotion recognition in non-demented sporadic ALS patients compared with healthy controls, and to explore for the first time its microstructural white-matter correlates. Twenty-two subjects with either probable or definite diagnosis of ALS and 55 age-, gender-, and education-matched healthy controls were recruited in the study. All participants performed the Ekman 60-Faces Test, assessing the recognition of six basic emotions (i.e., anger, disgust, fear, sadness, surprise and happiness). A subgroup of subjects, comprising 19 patients and 20 healthy controls, also underwent a Diffusion Tensor Imaging scanning. Behavioral analysis highlighted a significant decline of emotion recognition skills in patients compared to controls, particularly affecting the identification of negative emotions. Moreover, the Diffusion Tensor Imaging analyses revealed a correlation between this impairment and the alteration of white-matter integrity along the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. Our findings indicate the presence of an early emotion recognition deficit in non-demented sporadic ALS patients, associated with microstructural changes in ventral associative bundles connecting occipital, temporo-limbic and orbitofrontal regions in the right hemisphere. These changes may represent a frontotemporal-limbic microstructural marker of socio-emotional impairment in ALS.",Aged;Amyotrophic Lateral Sclerosis/ pathology/ psychology;Brain/ pathology/ultrastructure;Cognition Disorders/etiology/psychology;Diffusion Tensor Imaging;Emotions/ physiology;Facial Expression;Female;Humans;Male;Middle Aged;Psychomotor Performance/physiology;Recognition (Psychology)/ physiology;Social Perception,"Crespi, C.;Cerami, C.;Dodich, A.;Canessa, N.;Arpone, M.;Iannaccone, S.;Corbo, M.;Lunetta, C.;Scola, E.;Falini, A.;Cappa, S. F.",2014,Apr,10.1016/j.cortex.2014.01.002,0,
4827,Corpus callosal atrophy in premanifest and early Huntington's disease,"BACKGROUND: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. OBJECTIVES: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. METHODS: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A >/=10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. RESULTS: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. CONCLUSIONS: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.","Adult;Atrophy/pathology;Corpus Callosum/ pathology;Cross-Sectional Studies;Female;Humans;Huntington Disease/ pathology;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Prodromal Symptoms","Crawford, H. E.;Hobbs, N. Z.;Keogh, R.;Langbehn, D. R.;Frost, C.;Johnson, H.;Landwehrmeyer, B.;Reilmann, R.;Craufurd, D.;Stout, J. C.;Durr, A.;Leavitt, B. R.;Roos, R. A.;Tabrizi, S. J.;Scahill, R. I.",2013,,10.3233/jhd-130077,0,
4828,White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"BACKGROUND: Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. METHODS: We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. RESULTS: The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P<0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P<0.01), with most prominent axonal abnormalities observed in the frontal WM (P<0.05). The SIs of arterioles in CADASIL were increased by 25-45% throughout the regions assessed, with the highest change in the mid-frontal region (P=0.000). CONCLUSIONS: Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures.",Adult;Aged;Amyloid beta-Protein Precursor/metabolism;Axons/metabolism/ pathology;Brain/metabolism/pathology;CADASIL/metabolism/ pathology;Female;Frontal Lobe/metabolism/ pathology;Humans;Male;Middle Aged;Nerve Net/pathology;White Matter/blood supply/metabolism/ pathology,"Craggs, L. J.;Yamamoto, Y.;Ihara, M.;Fenwick, R.;Burke, M.;Oakley, A. E.;Roeber, S.;Duering, M.;Kretzschmar, H.;Kalaria, R. N.",2014,Aug,10.1111/nan.12073,0,
4829,Interaction of APOE e4 and poor glycemic control predicts white matter hyperintensity growth from 73 to 76,"We examined whether apolipoprotein E (APOE) status interacts with vascular risk factors (VRFs) to predict the progression of white matter hyperintensities (WMHs) on brain MRI scans over a specific period of life in older age when the risk of dementia increases. At age 73 years, baseline VRFs were assessed via self-reported history of diabetes, hypertension, smoking, and hypercholesterolemia, and via objective measures of blood HbA1c, body mass index, diastolic and systolic blood pressure, and blood high-density lipoprotein to total cholesterol (HDL) ratio. APOE e4 allele was coded as either present or absent. WMH progression was measured on MRI over 3 years in 434 older adults, in a same-year-of-birth cohort. APOE e4 carriers with either a self-reported diagnosis of diabetes (beta = 0.160, p = 0.002) or higher glycated hemoglobin levels (beta = 0.114, p = 0.014) exhibited greater WMH progression, and the former survived correction for multiple testing. All other APOE-VRF interactions were nonsignificant (betainteraction < 0.056, p > 0.228). The results suggest that carrying the APOE ""risk"" e4 allele increases the risk of greater age-related WMH progression over the early part of the eighth decade of life, when combined with poorer glycemic control. The interaction effect was robust to co-occurring VRFs, suggesting a possible target for mitigating brain and cognitive aging at this age.",Apoe;Aging;Brain MRI;Longitudinal;Vascular risk;White matter,"Cox, S. R.;Ritchie, S. J.;Dickie, D. A.;Pattie, A.;Royle, N. A.;Corley, J.;Aribisala, B. S.;Harris, S. E.;Valdes Hernandez, M.;Gow, A. J.;Munoz Maniega, S.;Starr, J. M.;Bastin, M. E.;Wardlaw, J. M.;Deary, I. J.",2017,Feb 27,,0,
4830,"Associations between education and brain structure at age 73 years, adjusted for age 11 IQ","Objective: To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11. Methods: We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ. Results: The significant relationship between education and average cortical thickness (β 0.124, p 0.004) was reduced by 23% when age 11 IQ was included (β 0.096, p 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy. Conclusions: The association between years of education and brain structure ≈60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health.",aged;article;brain;brain atrophy;brain scintiscanning;brain size;community care;cortical thickness (brain);education;female;fractional anisotropy;human;intelligence quotient;intelligence test;major clinical study;male;neuroimaging;nuclear magnetic resonance imaging;priority journal;white matter,"Cox, S. R.;Dickie, D. A.;Ritchie, S. J.;Karama, S.;Pattie, A.;Royle, N. A.;Corley, J.;Aribisala, B. S.;Valdés Hernández, M.;Muñoz Maniega, S.;Starr, J. M.;Bastin, M. E.;Evans, A. C.;Wardlaw, J. M.;Deary, I. J.",2016,,10.1212/wnl.0000000000003247,0,
4831,Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI,"Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation - that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age.",aged;article;diffusion weighted imaging;fractional anisotropy;frontal lobe;hippocampus;human;male;neuroimaging;normal human;prefrontal cortex;task performance;tractography;verbal memory;white matter,"Cox, S. R.;Bastin, M. E.;Ferguson, K. J.;Allerhand, M.;Royle, N. A.;Maniega, S. M.;Starr, J. M.;MacLullich, A. M. J.;Wardlaw, J. M.;Deary, I. J.;MacPherson, S. E.",2014,,,0,
4832,"White Matter Changes are Associated with Ventricular Expansion in Aging, Mild Cognitive Impairment, and Alzheimer's Disease","White matter lesions are highly prevalent in individuals with Alzheimer's disease (AD). Although these lesions are presumed to be of vascular origin and linked to small vessel disease in older adults, little information exists about their relationship to markers of classical AD neurodegeneration. Thus, we examined the link between these white matter changes (WMC) segmented on T1-weighted MRI and imaging markers presumed to be altered due to primary AD neurodegenerative processes. Tissue microstructure of WMC was quantified using diffusion tensor imaging and the relationship of WMC properties and volume to neuroimaging markers was examined in 219 cognitively healthy older adults and individuals with mild cognitive impairment and AD using data from the Alzheimer's Disease Neuroimaging Initiative. No significant group differences in WMC properties were found. However, there were strong associations between diffusivity of WMC and ventricular volume, volume of WMC and total WM volume. In comparison, group differences in parahippocampal white matter microstructure were found for all diffusion metrics and were largely explained by hippocampal volume. Factor analysis on neuroimaging markers suggested two independent sets of covarying degenerative changes, with potentially age- and vascular-mediated tissue damage contributing to one factor and classical neurodegenerative changes associated with AD contributing to a second factor. These data demonstrate two potentially distinct classes of degenerative change in AD, with one factor strongly linked to aging, ventricular expansion, and both volume and tissue properties of white matter lesions, while the other factor related to classical patterns of cortical and hippocampal neurodegeneration in AD.",,"Coutu, J. P.;Goldblatt, A.;Rosas, H. D.;Salat, D. H.",2015,,10.3233/jad-150306,0,
4833,Quantitative analysis of MRI signal intensity in new variant Creutzfeldt-Jakob disease,"High signal intensity within the posterior thalamus (pulvinar nucleus) has been noted on MRI in patients with new variant Creutzfeldt-Jakob disease (nvCJD). In this study MRI examinations from three patients with proven nvCJD were compared with MRI examinations from a control group of 14 age-matched subjects with no neurological abnormalities. Mean signal intensity from seven target areas (periaqueductal tissue, posterior thalamus, dorsomedial thalamus, anterior thalamus, putamen, caudate head and frontal white matter) was calculated in each case. Absolute signal intensity measurements were not significantly different between the groups. Patients with nvCJD showed significantly higher signal intensity within dorsomedial thalamus, posterior thalamus and periaqueductal region than control patients when these measurements were normalized to the signal intensity of normal appearing white matter. Highly significant differences in posterior thalamus/putamen signal intensity ratio (PPR) and posterior thalamus/caudate ratio (PCR) were observed between the groups. For proton density images, PPR and PCR were greater than 1 for all nvCJD patients and less than 1 for all control patients. Both PPR and PCR are simple to calculate and offer a simple, non-invasive indicator of nvCJD.",Adolescent;Adult;Brain/ pathology;Case-Control Studies;Creutzfeldt-Jakob Syndrome/ diagnosis;Humans;Magnetic Resonance Imaging;Thalamus/pathology,"Coulthard, A.;Hall, K.;English, P. T.;Ince, P. G.;Burn, D. J.;Bates, D.",1999,Aug,10.1259/bjr.72.860.10624339,0,
4834,Distribution of cranial MRI abnormalities in patients with symptomatic and subclinical CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cause of early stroke and dementia, with a poor prognosis. This study was performed to clarify lesion appearance and pattern of lesion distribution in CADASIL. 20 members of a single family were tested for the CADASIL gene mutation and studied with cranial MRI. Scans were evaluated for lesion load and pattern of lesion distribution. 19 patients had cranial MRI, of whom 11 had normal MRI scans, were clinically unaffected and tested negative for the CADASIL gene mutation. The remaining eight patients had abnormal cranial MRI scans: seven patients were positive for the CADASIL gene mutation and one (untested) patient was severely clinically affected. Three of the patients who tested positive for the CADASIL gene mutation were clinically unaffected at the time of imaging. All eight patients with abnormal cranial MRI had subcortical white matter abnormalities, mostly in frontal and temporal lobes. Lesions involving the corpus callosum were present on sagittal T2 weighted images in four of five clinically affected and one of three clinically unaffected patients. Lesions involving the deep grey nuclei and the brain stem were common. On T1 weighted images, lesions were either poorly defined (confluent white matter hypointensity) or well defined (cystic infarcts or enlarged perivascular spaces). Atrophy was infrequent. Familiarity with the range of cranial MRI appearances may aid diagnosis of CADASIL. Recognition of cranial imaging features in asymptomatic CADASIL patients could prompt earlier diagnosis.","Adult;Brain/ pathology;Dementia, Multi-Infarct/genetics/ pathology;Family;Genetic Testing;Humans;Magnetic Resonance Imaging/methods;Middle Aged","Coulthard, A.;Blank, S. C.;Bushby, K.;Kalaria, R. N.;Burn, D. J.",2000,Mar,10.1259/bjr.73.867.10817040,0,
4835,Regional brain distribution of translocator protein using (11)C DPA-713 PET in individuals infected with HIV,"Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test-retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings.","AIDS Dementia Complex/ metabolism/ radionuclide imaging/therapy;Acetamides;Adult;Anti-Retroviral Agents/therapeutic use;Biomarkers/metabolism;Brain/metabolism/radionuclide imaging/virology;Carbon Isotopes;Genotype;Humans;Microglia/metabolism;Middle Aged;Neuropsychological Tests;Phenotype;Positron-Emission Tomography/ methods;Pyrazoles;Pyrimidines;Receptors, GABA/genetics/ metabolism;Young Adult","Coughlin, J. M.;Wang, Y.;Ma, S.;Yue, C.;Kim, P. K.;Adams, A. V.;Roosa, H. V.;Gage, K. L.;Stathis, M.;Rais, R.;Rojas, C.;McGlothan, J. L.;Watkins, C. C.;Sacktor, N.;Guilarte, T. R.;Zhou, Y.;Sawa, A.;Slusher, B. S.;Caffo, B.;Kassiou, M.;Endres, C. J.;Pomper, M. G.",2014,Jun,10.1007/s13365-014-0239-5,0,
4836,MRI and CT of Kufs disease. A family form,"Kufs disease is the adult form of ceroid neurolipofuscinosis, and an uncommon cause of degenerative nervous system disease affecting young adults. We present here 4 cases of family form revealed by a demential syndrome. In all 4 patients MRI showed diffuse cortical atrophy predominant m the parietal regions. In 3 of these 4 patients MRI also exhibited a low signal in T2-weighted sequences on the putamens. There was no abnormality of the white matter. Diagnosis was made by cerebral biopsy in one case and by rectal biopsy in all other cases. Although the MRI images are not specific, they must be used when the diagnosis of Kufs disease is suspected in young patients with demential syndrome.",,"Cottier, J. P.;Perrier, D.;Sonier, C. B.;Yapo, P.;Ruchoux, M. M.;Gelot, A.;Laffont, J.;Larmande, P.",1996,1996,,0,
4837,[Pathology of small cerebral arteries demonstrated by MRI: a marker of aging?] Pathologie des petites arteres cerebrales mise en evidence par l'IRM: un marqueur du vieillissement ?,"Brain magnetic resonance imaging frequently identifies signal abnormalities in the white matter and cerebral cortex in the elderly. They are related to a degenerative disease of the small vessels that may be of ischemic (leukoaraiosis, lacunae and infarct) or hemorrhagic (microbleeds and hematomas) origin. These lesions are part of the aging process, and compounded by vascular risk factors. They increase the occurrence frequency and severity of ischemic or hemorrhagic stroke. Their importance is also associated with the presence of cognitive and/or affective symptoms, and their impact on the occurrence and evolution of dementia remains to be evaluated. The visible consequences of this microangiopathy on MRI probably represent the focal mark of a widespread cerebrovascular disease in the brain parenchyma.",Age Factors;Aged;Brain/blood supply/pathology;Brain Ischemia/ pathology;Cerebral Amyloid Angiopathy/pathology;Cerebral Arteries/ pathology;Cerebral Hemorrhage/ pathology;Dementia/pathology;Humans;Magnetic Resonance Angiography;Stroke/ pathology;White Matter/blood supply/pathology,"Cottier, J. P.;Edjlali, M.;Gaillard, M. A.;Domengie, F.;Aljishi, A.;Casals, X.;Herbreteau, D.;Hommet, C.",2011,Dec,,0,
4838,Pathology of small cerebral arteries demonstrated by MRI: a marker of aging?,"Brain magnetic resonance imaging frequently identifies signal abnormalities in the white matter and cerebral cortex in the elderly. They are related to a degenerative disease of the small vessels that may be of ischemic (leukoaraiosis, lacunae and infarct) or hemorrhagic (microbleeds and hematomas) origin. These lesions are part of the aging process, and compounded by vascular risk factors. They increase the occurrence frequency and severity of ischemic or hemorrhagic stroke. Their importance is also associated with the presence of cognitive and/or affective symptoms, and their impact on the occurrence and evolution of dementia remains to be evaluated. The visible consequences of this microangiopathy on MRI probably represent the focal mark of a widespread cerebrovascular disease in the brain parenchyma.",Age Factors;Aged;Brain/blood supply/pathology;Brain Ischemia/ pathology;Cerebral Amyloid Angiopathy/pathology;Cerebral Arteries/ pathology;Cerebral Hemorrhage/ pathology;Dementia/pathology;Humans;Magnetic Resonance Angiography;Stroke/ pathology;White Matter/blood supply/pathology,"Cottier, J. P.;Edjlali, M.;Gaillard, M. A.;Domengie, F.;Aljishi, A.;Casals, X.;Herbreteau, D.;Hommet, C.",2011,Dec,10.1684/pnv.2011.0301,0,
4839,Electron microscopy analysis of skin biopsies in CADASIL disease,"Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited vascular disorder, non-amyloid and non-atherosclerotic, affecting predominantly the central nervous system. We examined samples of skin biopsies from six patients (men, 43-52-year-old), admitted for treatment in the Neurology Clinic regarding the presence of partial motor impairment on upper and lower right limbs, facial asymmetry and phrasing impairment (three of the patients); These three patients had family history remarkable for early-onset strokes: mother and two brothers deceased by early strokes (40-50-year-old). Skin biopsy samples were fixed in glutaraldehyde and post-fixed in osmium tetroxyde. After dehydration, tissue samples were embedded in Epon. Ultrathin sections were mounted on copper grids and stained with uranyl acetate and lead citrate as usual and examined with a transmission electron microscope Phillips CM100. In all cases ultrastructural study showed granular osmiophilic material (GOM) in extracellular locations, between degenerating smooth muscle cells in dermal arteries or in their indentations. Deposits of GOM varied in size and electron density. Degeneration and loss of smooth muscle cells (SMCs) leads to abnormal enlargement of the space between these cells Ultrastructural analysis in three cases showed chromatin condensation and peripheral aggregation of nuclear material suggesting cells entry to apoptosis. These aspects and the marked destruction of the vascular wall were correlated with MRI findings and the severity of clinical manifestations at these patients. Our study showed that findings of GOM deposits, degeneration and loss of SMCs (probably by apoptosis), cell adhesion elements disturbance are characteristic for CADASIL disease and sufficient for diagnose of certainty. Moreover, electron microscopy analysis of skin biopsies is a useful tool for a differential diagnosis and can be considered as first choice method.","Adult;Biopsy;CADASIL/*pathology;Humans;Male;*Microscopy, Electron;Middle Aged;Myocytes, Smooth Muscle/pathology/ultrastructure;Skin/*pathology/*ultrastructure","Cotrutz, C. E.;Indrei, A.;Badescu, L.;Dacalu, C.;Neamtu, M.;Dumitrescu, G. F.;Stefanache, F.;Petreus, T.",2010,,,0,
4840,Radionuclide brain imaging in acquired immunodeficiency syndrome (AIDS),"Infection with the human immunodeficiency virus-type 1 (HIV-1) may produce a variety of central nervous system (CNS) symptoms and signs. CNS involvement in patients with the acquired immunodeficiency syndrome (AIDS) includes AIDS dementia complex or HIV-1 associated cognitive/motor complex (widely known as HIV encephalopathy), progressive multifocal leucoencephalopathy (PML), opportunistic infections such as Toxoplasma gondii, TB, Cryptococcus and infiltration by non-Hodgkin's B cell lymphoma. High resolution structural imaging investigations, either X-ray Computed Tomography (CT scan) or Magnetic Resonance Imaging (MRI) have contributed to the understanding and definition of cerebral damage caused by HIV encephalopathy. Atrophy and mainly high signal scattered white matter abnormalities are commonly seen with MRI. PML produces focal white matter high signal abnormalities due to multiple foci of demyelination. However, using structural imaging techniques there are no reliable parameters to distinguish focal lesions due to opportunistic infection (Toxoplasma gondii abscess) from neoplasm (lymphoma infiltration). In this manuscript we review the use of radionuclide brain imaging techniques in the investigation of HIV infected patients. Brain perfusion single photon emission tomography (SPET), neuroreceptor and positron emission tomography (PET) studies are reviewed. Greater emphasis is put on the potential of some radiopharmaceuticals, considered to be brain tumor markers, to distinguish intracerebral lymphoma infiltration from Toxoplasma infection. SPET with 201Tl using quantification (tumour to nontumour radioactivity ratios) appears a very promising technique to identify intracerebral lymphoma.",AIDS Dementia Complex/radionuclide imaging;AIDS-Related Opportunistic Infections/radionuclide imaging;Acquired Immunodeficiency Syndrome/complications/ radionuclide imaging;Brain/ radionuclide imaging;Brain Diseases/complications/radionuclide imaging;Brain Neoplasms/radionuclide imaging;Humans,"Costa, D. C.;Gacinovic, S.;Miller, R. F.",1995,Sep,,0,
4841,Circadian sleep/wake rhythm abnormalities as a risk factor of a poststroke apathy,"Background: Poststroke apathy affects 19-55% of patients following stroke and has a negative impact on functional recovery, general health, and quality of life, as well as being a source of significant burden for caregivers. Aims: A major clinical issue is the delayed diagnosis of poststroke apathy, and so the aim of our study is to evaluate the relationship between early poststroke alterations of circadian rhythms of sleep/wake cycles and the occurrence of poststroke apathy. Methods: Forty-six patients with a recent magnetic resonance imaging confirmed stroke were included. Main exclusion criteria were a mild to severe disability impeding home discharge from the hospital and the presence of apathy or dementia before stroke. Cerebrovascular lesions were evaluated by magnetic resonance imaging. At hospital discharge, an actigraph was used to measure patient's global activity as well as parameters of circadian rhythmicity (relative amplitude, interdaily stability, intradaily variability) and sleep (sleep duration, sleep efficiency, fragmentation index) over seven-days. Apathy was assessed at hospital discharge as well as at three-months using the Apathy Inventory and the Lille Apathy Rating Scale. Results: Of the 46 patients evaluated, 10 (22%) showed apathy three-months after stroke (median Apathy Inventory=4·5). Before inclusion, these 10 subjects did not differ significantly from other patients concerning their sleep and, at inclusion, they did not differ concerning apathy, anxiety, depression, or cognitive and functional abilities. However, actigraphy measured at discharged identified significant alterations of sleep (P<0·005). Future poststroke apathy patients exhibited a decrease in sleep efficiency (actual sleep time expressed as a percentage of time in bed) and an increase in the fragmentation index (degree of fragmentation during the sleep period) at three-months. No association was observed between poststroke apathy and the characteristics of cerebrovascular lesions (stroke location, extent of leucoencephalopathy, number of lacunes and microbleeds). Conclusion: These results indicate that early poststroke alterations of sleep/wake circadian rhythms - easily evaluated by actigraphy - are associated with a higher risk of poststroke apathy at three-months. In terms of clinical outcomes, our results provide targets for very early identification of patients at risk to develop apathy after stroke and for assessing when to start specific therapy to optimize rehabilitation efficiency.",,"Cosin, C.;Sibon, I.;Poli, M.;Allard, M.;Debruxelles, S.;Renou, P.;Rouanet, F.;Mayo, W.",2015,1,,0,
4842,Cannabinoid receptor expression in HIV encephalitis and HIV-associated neuropathologic comorbidities,"AIMS: Cannabinoids have been proposed for treating various neurodegenerative disorders and as adjunct therapy for HIV+ patients with neurologic sequelae. The expression of cannabinoid receptors (CB1 and CB2) has been reported in neurodegenerative diseases and in simian immunodeficiency virus encephalitis, yet the receptor expression in the central nervous system of HIV+ individuals is not known. METHODS: An anti-CB1 antibody and two anti-CB2 antibodies were employed for immunohistochemistry in the cerebral cortex and white matter of HIV encephalitis (HIVE) and HIV-associated comorbidities, as well as control brains (HIV- and HIV+). RESULTS: By quantitative image analysis, we observed that CB1 was increased in HIVE brains and those with comorbidities, while CB2 was significantly increased in the white matter of HIVE. Morphologically, CB1 was present in neurones, and both CB1 and CB2 were present in meningeal macrophages and subpial glia in all brains. In HIVE, CB1 was found in white matter microglia and perivascular cells, while CB2 was increased in microglia, astrocytes and perivascular macrophages. Double immunofluorescence with cell-specific markers and immunoblots on primary cultured microglia and astrocytes substantiated the glial localization of the cannabinoid receptors and specificity of the antibodies. CONCLUSIONS: Our study indicates that cannabinoid receptor expression occurs in glia in HIVE brains, and this may have ramifications for the potential use of cannabinoid ligands in HIV-infected patients.","AIDS Dementia Complex/epidemiology/ metabolism;Adult;Brain/metabolism/pathology;Comorbidity;Female;Fluorescent Antibody Technique;Humans;Image Interpretation, Computer-Assisted;Immunoblotting;Immunohistochemistry;Male;Middle Aged;Neuroglia/metabolism;Receptor, Cannabinoid, CB1/ biosynthesis;Receptor, Cannabinoid, CB2/ biosynthesis","Cosenza-Nashat, M. A.;Bauman, A.;Zhao, M. L.;Morgello, S.;Suh, H. S.;Lee, S. C.",2011,Aug,10.1111/j.1365-2990.2011.01177.x,0,
4843,"Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain","Aims: Microglia are involved in neurodegeneration, are prime targets for anti-inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells. Methods: We sought to elucidate the protein expression in normal human central nervous system, several neurological diseases (HIV encephalitis, Alzheimer's disease, multiple sclerosis and stroke) and simian immunodeficiency virus encephalitis by performing immunohistochemistry with two anti-TSPO antibodies. Results: Although the overall parenchymal staining was minimal in normal brain, endothelial and smooth muscle cells, subpial glia, intravascular monocytes and ependymal cells were TSPO-positive. In disease states, elevated TSPO was present in parenchymal microglia, macrophages and some hypertrophic astrocytes, but the distribution of TSPO varied depending on the disease, disease stage and proximity to the lesion or relation to infection. Staining with the two antibodies correlated well in white matter, but one antibody also stained cortical neurones. Quantitative analysis demonstrated a significant increase in TSPO in the white matter of HIV encephalitis compared with brains without encephalitis. TSPO expression was also increased in simian immunodeficiency virus encephalitis. Conclusions: This report provides the first comprehensive immunohistochemical analysis of the expression of TSPO. The results are useful for informing the usage of positron emission tomography as an imaging modality and have an impact on the potential use of TSPO as an anti-inflammatory pharmacological target. © 2009 Blackwell Publishing Ltd.",,"Cosenza-Nashat, M.;Zhao, M. L.;Suh, H. S.;Morgan, J.;Natividad, R.;Morgello, S.;Lee, S. C.",2009,June,,0,
4844,Clock drawing errors in dementia: neuropsychological and neuroanatomical considerations,"OBJECTIVES: A clock drawing test scoring system is presented to explore the neuropsychological/neuroanatomic components underlying clock drawing in patients initially diagnosed with Alzheimer disease, ischemic vascular dementia associated with white matter alterations, and Parkinson disease. METHODS: Fourteen clock drawing test errors were scored to create 4 clock drawing test subscales that assess different underlying cognitive operations. RESULTS: In the command condition, errors on the Time subscale were correlated with impairment on executive control measures. In the copy condition, errors on the Perseveration/Pull to Stimulus subscale was also correlated with executive control measures. Patients presenting with mild (low) magnetic resonance imaging white matter alterations, significant (high) white matter alterations, and Parkinson disease were compared. In the command condition, the low white matter alterations group made fewer total errors than the Parkinson disease group. In the copy condition, the low white matter alterations group made fewer errors on the Time, Spatial Layout, and Perseveration/Pull to Stimulus clock drawing test subscales than the high white matter alterations or Parkinson disease groups. Few differences were noted between the high white matter alterations and Parkinson disease groups. DISCUSSION: Our data suggest that heavy demands on executive control associated with the interruption of large-scale cortical-subcortical neural networks underlie impairment in clock drawing in mild dementia.","Aged;Aged, 80 and over;Art;Dementia/complications/ psychology;Female;Humans;Male;Motor Skills Disorders/ etiology;Nerve Net;Neuropsychological Tests;Time Perception;Writing","Cosentino, S.;Jefferson, A.;Chute, D. L.;Kaplan, E.;Libon, D. J.",2004,Jun,,0,
4845,Proton MR spectroscopy of brain abnormalities in neonates born to HIV-positive mothers,"PURPOSE: To examine the sensitivity of proton MR spectroscopy for detecting early central nervous system abnormalities in neonates born to human immunodeficiency virus (HIV)-positive mothers. METHODS: Asleep, unsedated, and continuously monitored by electrocardiography, 10 newborns, 5 with HIV-positive and 5 with HIV-negative mothers, were studied within the first 10 days of life in a 1.5-T scanner. After T1- and T2-weighted images were obtained, proton spectra were performed using voxels of interest (3.4 cm3) in the deep parietooccipital white matter. Peaks were identified as N-acetyl-aspartate (2.0 ppm), creatine and phosphocreatine (3.0 ppm), choline (3.2 ppm), and inositol (3.5 ppm). Peak areas were used to calculate metabolic ratios: N-acetyl-aspartate to creatine, inositol to creatine, and creatine to choline. RESULTS: All newborns of HIV-positive mothers had abnormal proton spectra compared with control infants; a nonspecific amino acid peak in the 2.1- to 2.6-ppm area was elevated, broad, and overlapping the N-acetyl-aspartate peak in all the HIV-exposed newborns and in only 1 of the 5 control newborns. The choline-to-creatine ratio was higher in HIV-exposed newborns at 2.3 +/- 0.4 (normal term, 0.9 +/- 0.3), as was the N-acetyl-aspartate-to-creatine ratio at 2.6 +/- 0.9 (for control subjects, 1.2 +/- 0.4). MR images from these brain regions were all considered normal. Because acquired immunodeficiency syndrome develops in only a small fraction of neonates born to HIV-seropositive mothers, the above spectral abnormalities found in all our subjects may result from indirect effects of HIV, such as intrauterine growth retardation. CONCLUSIONS: These findings indicate that proton MR spectroscopy might play an important role in detecting early central nervous system complications in newborns of HIV-seropositive mothers.","AIDS Dementia Complex/ diagnosis;Aspartic Acid/analogs & derivatives/metabolism;Choline/metabolism;Diagnosis, Differential;Energy Metabolism/ physiology;Female;Fetal Growth Retardation/diagnosis;HIV Seropositivity/ diagnosis/transmission;Humans;Infant, Newborn;Infectious Disease Transmission, Vertical;Inositol/metabolism;Magnetic Resonance Imaging/ methods;Magnetic Resonance Spectroscopy/ methods;Male;Occipital Lobe/pathology;Parietal Lobe/pathology;Phosphocreatine/metabolism","Cortey, A.;Jarvik, J. G.;Lenkinski, R. E.;Grossman, R. I.;Frank, I.;Delivoria-Papadopoulos, M.",1994,Nov,,0,
4846,Spatial data analysis in the quantitative assessment of cerebral white matter pathology on MRI in HIV infection,"This study was carried out using MRI (proton density--and T2-weighted) on 16 HIV-negative controls, 9 symptom-free HIV-positive patients and 25 with CDC IV HIV disease. The studies from this last group had previously been allocated by a radiologist to the following categories: 8 with focal mass lesions and normal-appearing white matter; 9 with diffuse encephalopathy (high signal on T2-weighted images, affecting most or all of the white matter) and 8 with patchy encephalopathy (high signal affecting only one or two areas within the white matter). Moran's I, a statistic of spatial autocorrelation, was calculated for the grey-scale values of a sampled pixel array from a central white matter region of each of the images. All values of Moran's I calculated in this study showed a large positive excess over the expected value under randomisation, indicating highly significant positive auto-correlation in the spatial arrangement of the grey-scale values. On T2-weighted images a statistically significant increase in the mean value of Moran's I, compared with controls, was found in the diffuse encephalopathy group, indicating that quantifiable changes in the spatial autocorrelation of pixel data can be related to recognised qualitative changes in the appearance of white matter in subjects with HIV disease. A lesser, but significant, rise in the mean value of Moran's I was also found in the focal mass lesion group, suggesting that changes in spatial autocorrelation may indicate pathological change in advance of qualitative MRI changes.","AIDS Dementia Complex/ diagnosis;Brain/ pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Demyelinating Diseases/diagnosis;Diagnosis, Differential;Hiv-1;Humans;Magnetic Resonance Imaging/ methods;Neuropsychological Tests","Corrigall, R. J.;Chong, W. K.;Paley, M.;Wilkinson, I. D.;Lantos, P.;Everall, I.",1995,Aug,,0,
4847,"Longitudinal evaluation of resting-state connectivity, white matter integrity and cortical thickness in stable HIV infection: Preliminary results","Purpose The objectives of this study were to determine if HIV-infected patients treated with highly active antiretroviral therapy (HAART), without dementia, suffer from longitudinal gray matter (GM) volume loss, changes in white matter (WM) integrity and deterioration in functional connectivity at rest, in an average interval of 30 months. Methods Clinically stable HIV-positive patients (on HAART, CD4 + T lymphocyte > 200 cells/mul, and viral loads <50 copies/mul) were recruited. None of them had HIV-associated dementia. Each patient underwent two scans, performed in a 1.5-T magnetic resonance imaging (MRI) scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of GM structures. WM integrity was assessed using tract-based spatial statistics to post-process diffusion tensor imaging data, and FMRIB's Software Library tools were used to post-process resting-state functional magnetic resonance imaging (RS-fMRI). Results There were no significant differences in cortical thickness, deep GM volumes, or diffusivity parameters between the scans at the two time points. Five resting-state networks were identified in our patients. In the second MRI, HIV-positive patients presented increased areas of functional connectivity in visual pathways, frontoparietal and cerebellar networks, compared with the first MRI (considering p < 0.05). Conclusions RS-fMRI revealed potentially compensatory longitudinal alterations in the brains of HIV-positive patients, attempting to compensate for brain damage related to the infection.",Hiv;cortical thickness;diffusion tensor imaging;longitudinal follow-up;resting-state functional imaging,"Correa, D. G.;Zimmermann, N.;Ventura, N.;Tukamoto, G.;Doring, T.;Leite, S. C.;Fonseca, R. P.;Bahia, P. R.;Lopes, F. C.;Gasparetto, E. L.",2017,Dec,,0,
4848,"Longitudinal assessment of subcortical gray matter volume, cortical thickness, and white matter integrity in HIV-positive patients","PURPOSE: To longitudinally evaluate the cortical thickness and deep gray matter structures volume, measured from T1 three-dimensional (3D) Gradient echo-weighted imaging, and white matter integrity, assessed from diffusion tensor imaging (DTI) of HIV-positive patients. MATERIALS AND METHODS: Twenty-one HIV-positive patients on stable highly active antiretroviral therapy (HAART) with CD4+ T lymphocytes count >200 cells/mL and viral load <50 copies/mL underwent two magnetic resonance imaging (MRI) scans with a median interval of 26.6 months. None of the patients had HIV-related dementia. T1 3D magnetization prepared rapid gradient echo-weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5 Tesla MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract-based spatial statistics analysis, a white matter skeleton was created, and a permutation-based inference with 5000 permutations, with a threshold of P < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The median, radial, and axial diffusivities were also projected onto the mean FA skeleton. RESULTS: There were no significant differences in cortical thickness, deep gray matter structures volumes or diffusivity parameters between scans at the two time points (considering P < 0.05). CONCLUSION: No longitudinal differences in cortical thickness, deep gray matter volumes, or white matter integrity were observed in an HIV-positive population on stable HAART, with undetectable viral load and high CD4+ T lymphocytes count. J. Magn. Reson. Imaging 2016;44:1262-1269.","Adult;Antiretroviral Therapy, Highly Active/methods;Diffusion Tensor Imaging/ methods;Encephalitis, Viral/ drug therapy/immunology/ pathology;Female;Gray Matter/immunology/ pathology;HIV Infections/ drug therapy/immunology/ pathology;Humans;Longitudinal Studies;Male;Middle Aged;Organ Size/immunology;Treatment Outcome;Viral Load/immunology;White Matter/immunology/ pathology;Hiv;HIV-associated neurocognitive disorders;cortical thickness;diffusion tensor imaging;longitudinal follow-up","Correa, D. G.;Zimmermann, N.;Tukamoto, G.;Doring, T.;Ventura, N.;Leite, S. C.;Cabral, R. F.;Fonseca, R. P.;Bahia, P. R.;Gasparetto, E. L.",2016,Nov,,0,4849
4849,"Longitudinal assessment of subcortical gray matter volume, cortical thickness, and white matter integrity in HIV-positive patients","PURPOSE: To longitudinally evaluate the cortical thickness and deep gray matter structures volume, measured from T1 three-dimensional (3D) Gradient echo-weighted imaging, and white matter integrity, assessed from diffusion tensor imaging (DTI) of HIV-positive patients. MATERIALS AND METHODS: Twenty-one HIV-positive patients on stable highly active antiretroviral therapy (HAART) with CD4+ T lymphocytes count >200 cells/mL and viral load <50 copies/mL underwent two magnetic resonance imaging (MRI) scans with a median interval of 26.6 months. None of the patients had HIV-related dementia. T1 3D magnetization prepared rapid gradient echo-weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5 Tesla MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract-based spatial statistics analysis, a white matter skeleton was created, and a permutation-based inference with 5000 permutations, with a threshold of P < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The median, radial, and axial diffusivities were also projected onto the mean FA skeleton. RESULTS: There were no significant differences in cortical thickness, deep gray matter structures volumes or diffusivity parameters between scans at the two time points (considering P < 0.05). CONCLUSION: No longitudinal differences in cortical thickness, deep gray matter volumes, or white matter integrity were observed in an HIV-positive population on stable HAART, with undetectable viral load and high CD4+ T lymphocytes count. J. Magn. Reson. Imaging 2016.",,"Correa, D. G.;Zimmermann, N.;Tukamoto, G.;Doring, T.;Ventura, N.;Leite, S. C.;Cabral, R. F.;Fonseca, R. P.;Bahia, P. R.;Gasparetto, E. L.",2016,Apr 15,10.1002/jmri.25263,0,
4850,Multi-modal MRI in normal pressure hydrocephalus identifies pre-operative haemodynamic and diffusion coefficient changes in normal appearing white matter correlating with surgical outcome,"Magnetic resonance techniques were used to investigate haemodynamic abnormalities and their consequences in normal pressure hydrocephalus (NPH) and to assess changes in these parameters following surgery. Eleven patients with NPH were studied pre- and post-operatively using perfusion and diffusion weighted imaging and compared with ten age-matched controls. Pre-operative periventricular relative cerebral blood volume (rCBV) was reduced in patients (0.76±0.11) compared with control (1.16±0.16, P<0.01). There was no difference between outcome groups and no change in haemodynamic parameters following surgery. The periventricular apparent diffusion coefficient (ADC) was elevated in the poor outcome group (1.67±0.3×10(-3) mm(2) s(-1)) compared with both controls (1.04±0.4×10(-3) mm(2) s(-1), P<0.05) and the good outcome group (0.99±0.3×10(-3) mm(2) s(-1), P<0.05) despite appearing normal on conventional imaging. In white matter hyperintensities (WMH), rCBV was reduced (0.70±0.12 vs. 1.00±0.10, P<0.01), and the ADC was increased (1.98±0.6 vs. 1.04±0.4×10(-3) mm(2) s(-1), P<0.05) compared with the same anatomical location in controls. As low rCBV and high ADC is characteristic of chronic infarction, the findings in WMH regions suggest they are irreversibly damaged. Normal appearing periventricular tissue rCBV was reduced, implying that significant haemodynamic consequences contribute to symptoms in NPH. The elevated pre-operative ADC of the same region, was correlated with poor outcome, and may, therefore, be useful in selecting patients for surgery. © 2003 Elsevier Science B.V. All rights reserved.",,"Corkill, R. G.;Garnett, M. R.;Blamire, A. M.;Rajagopalan, B.;Cadoux-Hudson, T. A. D.;Styles, P.",2003,July,,0,
4851,Diagnosis of X-adrenoleucodystrophy phenotypic variants,"We report the radiological and biochemical data of a familial X-adrenoleucodystrophy with an extreme phenotypic variability, in which the diagnosis of several affected members was delayed for several years. The propositus developed a progressive dementia while two of his brothers were diagnosed of primary Addison's disease several years previously. MRI in two cases with different phenotypes revealed hyperintense diffuse white matter lesions, and the diagnosis was confirmed by increased serum levels of very long chain fatty acids. We conclude that X-adrenoleucodystrophy should be included in the differential diagnosis of adult Addison's disease even though no neurological involvement or family history is recorded, and that MRI is a useful tool for diagnosis and follow-up of neurological involvement in this disease.",Addison disease;adrenoleukodystrophy;adult;article;case report;controlled study;dementia;familial disease;female;human;human tissue;male;priority journal,"Coria, F.;Garcia-Viejo, M. A.;Delgado, J. A.;Duarte, J.;Claveria, L. E.;Giros, M.;Pampols, T.",1993,,,0,
4852,Brain microbleeds,"Brain microbleeds are small dot-like lesions appearing as hyposignal on gradient echo T2* MR sequences. They represent microscopic areas of old haemosiderin deposits. They are frequent in the setting of symptomatic cerebrovascular disease and also in older healthy people, suggesting a link with cerebral amyloid angiopathy. Their use as diagnostic or prognostic biomarkers remains uncertain. More recently, they have been highlighted as a potential key factor in the pathogenesis of Alzheimer's disease, connecting the main pathological contributors of amyloid accumulation and cerebrovascular damage. The increasing use of MRI in clinical practice and research has brought brain microbleeds very much to our attention, raising many clinical dilemmas, such as-what do they mean? Should I treat a patient with antithrombotic drugs or thrombolysis? And many others.","Alzheimer Disease/complications;Anti-Inflammatory Agents, Non-Steroidal/administration & dosage;Anticoagulants/administration & dosage;Aspirin/administration & dosage;Brain/*pathology;Cerebral Amyloid Angiopathy/complications/pathology;Humans;Intracranial Hemorrhages/*diagnosis/etiology;Magnetic Resonance Imaging/methods;Warfarin/administration & dosage","Cordonnier, C.",2010,Apr,10.1136/jnnp.2010.206086,0,
4853,Short TE quantitative proton magnetic resonance spectroscopy in variant Creutzfeldt-Jakob disease,"Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder. Clinical diagnosis is difficult in the early stages as the disease often presents with non-specific psychiatric and neurological symptoms. To investigate the diagnostic potential of quantitative short TE in vivo MRS, and the nature and anatomical distribution of biochemical abnormalities in vCJD, localised single-voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions: thalami, caudate nuclei and frontal white matter. Metabolite concentrations and ratios from three patients with definite or probable vCJD were compared with eight normal age-matched controls. Abnormal signal on T2-weighted MRI was apparent in the pulvinar region in all vCJD patients; this region also showed greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N-acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate nuclei. The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination.","Adult;Aspartic Acid/analogs & derivatives/metabolism;Case-Control Studies;Choline/metabolism;Creatine/metabolism;Creutzfeldt-Jakob Syndrome/*metabolism;Female;Glutamic Acid/metabolism;Humans;Inositol/metabolism;Magnetic Resonance Spectroscopy/*methods;Male;Phosphocreatine/metabolism;Protons;Statistics, Nonparametric","Cordery, R. J.;MacManus, D.;Godbolt, A.;Rossor, M. N.;Waldman, A. D.",2006,Aug,10.1007/s00330-005-0090-4,0,
4854,Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory,"Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized beta: -0.071+/-0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained approximately 41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.","Aged, 80 and over;Aorta, Thoracic/*physiopathology;Blood Pressure;Brain/pathology;Cerebrovascular Circulation/*physiology;Cerebrovascular Disorders/complications/diagnosis/*physiopathology;Cognition/*physiology;Cognition Disorders/diagnosis/*etiology/physiopathology;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Memory/*physiology;Pulsatile Flow;Pulse Wave Analysis;Vascular Stiffness/*physiology;cognition;dementia;hemodynamics;memory;vascular stiffness","Cooper, L. L.;Woodard, T.;Sigurdsson, S.;van Buchem, M. A.;Torjesen, A. A.;Inker, L. A.;Aspelund, T.;Eiriksdottir, G.;Harris, T. B.;Gudnason, V.;Launer, L. J.;Mitchell, G. F.",2016,Jan,10.1161/hypertensionaha.115.06398,0,
4855,Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment,"OBJECTIVE: Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer's disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. METHOD: Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored <26 were defined as ""probable MCI"" while those who scored ≥26 were labeled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus, and all four lobes were compared using multivariate analysis of variance (MANOVA). Regression analyses examined the relationship between DTI indices and total MoCA score. RESULTS: RESULTS revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine, and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. CONCLUSIONS: RESULTS indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer's disease and anterior brain aging patterns.",aged;anisotropy;brain;cognitive defect;diffusion tensor imaging;female;human;image processing;longitudinal study;male;middle aged;multivariate analysis;neuropsychological test;pathology;regression analysis;white matter,"Cooley, S. A.;Cabeen, R. P.;Laidlaw, D. H.;Conturo, T. E.;Lane, E. M.;Heaps, J. M.;Bolzenius, J. D.;Baker, L. M.;Salminen, L. E.;Scott, S. E.;Paul, R. H.",2015,,10.1080/13803395.2014.985636,0,
4856,Relating brain anatomy and cognitive ability using a multivariate multimodal framework,"Linking structural neuroimaging data from multiple modalities to cognitive performance is an important challenge for cognitive neuroscience. In this study we examined the relationship between verbal fluency performance and neuroanatomy in 54 patients with frontotemporal degeneration (FTD) and 15 age-matched controls, all of whom had T1- and diffusion-weighted imaging. Our goal was to incorporate measures of both gray matter (voxel-based cortical thickness) and white matter (fractional anisotropy) into a single statistical model that relates to behavioral performance. We first used eigenanatomy to define data-driven regions of interest (DD-ROIs) for both gray matter and white matter. Eigenanatomy is a multivariate dimensionality reduction approach that identifies spatially smooth, unsigned principal components that explain the maximal amount of variance across subjects. We then used a statistical model selection procedure to see which of these DD-ROIs best modeled performance on verbal fluency tasks hypothesized to rely on distinct components of a large-scale neural network that support language: category fluency requires a semantic-guided search and is hypothesized to rely primarily on temporal cortices that support lexical-semantic representations; letter-guided fluency requires a strategic mental search and is hypothesized to require executive resources to support a more demanding search process, which depends on prefrontal cortex in addition to temporal network components that support lexical representations. We observed that both types of verbal fluency performance are best described by a network that includes a combination of gray matter and white matter. For category fluency, the identified regions included bilateral temporal cortex and a white matter region including left inferior longitudinal fasciculus and frontal-occipital fasciculus. For letter fluency, a left temporal lobe region was also selected, and also regions of frontal cortex. These results are consistent with our hypothesized neuroanatomical models of language processing and its breakdown in FTD. We conclude that clustering the data with eigenanatomy before performing linear regression is a promising tool for multimodal data analysis.","Aged;Brain/ pathology;Cognition;Female;Frontotemporal Lobar Degeneration/pathology;Gray Matter/physiology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Multivariate Analysis;Nerve Net/physiology;Neuropsychological Tests;Reproducibility of Results;Verbal Behavior/physiology;White Matter/pathology","Cook, P. A.;McMillan, C. T.;Avants, B. B.;Peelle, J. E.;Gee, J. C.;Grossman, M.",2014,Oct 1,10.1016/j.neuroimage.2014.05.008,0,
4857,(1)H and (31)p magnetic resonance spectroscopic imaging of white matter signal hyperintensity areas in elderly subjects,"White matter signal hyperintensities (WMSH) are commonly seen on MRI of elderly subjects. The purpose of this study was to characterize metabolic changes in the white matter of elderly subjects with extensive WMSH. We used water-suppressed proton ((1)H) magnetic resonance spectroscopic imaging (MRSI) to compare six subjects with extensive WMSH with eight age-matched elderly subjects with minimal or absent WMSH, and phosphorus ((31)p) MRSI to compare nine subjects with extensive WMSH and seven age-matched elderly subjects without extensive WMSH. Relative to region-matched tissue in elderly controls, extensive WMSH were associated with increased signal from choline-containing metabolites, no significant change of signal from N-acetylaspartate, and a trend to a decreased phosphomonoester (PME) resonance. These findings suggest that WMSH may be associated with an alteration of brain myelin phospholipids in the absence of axonal damage. There were no differences in energy phosphates, consistent with lack of ongoing brain ischemia. Within the group with extensive WMSH, PME resonance measures were significantly lower in WMSH than in contralateral normal-appearing white matter. These results provide information on pathophysiology of WMSH and a basis for comparison with WMSH in Alzheimer's disease, vascular dementia, multiple sclerosis, and other diseases.",,"Constans, J. M.;Meyerhoff, D. J.;Norman, D.;Fein, G.;Weiner, M. W.",1995,1995,,0,
4858,H-1 MR spectroscopic imaging of white matter signal hyperintensities: Alzheimer disease and ischemic vascular dementia,"PURPOSE: To investigate the association of white matter signal hyperintensities (WMSHs) with changes in hydrogen-1 metabolites. MATERIALS AND METHODS: T2-weighted magnetic resonance (MR) imaging and H-1 MR spectroscopic imaging were performed in 21 elderly control subjects without or with minimal WMSHs, eight elderly subjects with substantial WMSHs, 11 probable Alzheimer disease patients with WMSHs, and eight ischemic vascular dementia (IVD) patients with WMSHs. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and creatine-containing metabolites (Cr) were analyzed. RESULTS: Differences in regional metabolite levels were found within the supraventricular brain of elderly control subjects. In Alzheimer disease patients, extensive WMSHs showed a lower percentage of NAA and a higher percentage of Cho compared with contralateral normal-appearing white matter (NAWM); in IVD patients, extensive and large WMSHs were associated with a higher percentage of Cho and a lower percentage of Cr compared with contralateral NAWM. CONCLUSION: Regional metabolite variation and the presence of WMSHs are important covariants that must be accounted for in analysis of MR spectroscopic data.","Aged;Alzheimer Disease/ metabolism/pathology;Aspartic Acid/analogs & derivatives/metabolism;Brain/metabolism/pathology;Brain Diseases/ metabolism/pathology;Brain Ischemia/ metabolism/pathology;Case-Control Studies;Cerebral Ventricles/metabolism/pathology;Choline/metabolism;Creatine/metabolism;Dementia/metabolism/pathology;Dementia, Vascular/ metabolism/pathology;Female;Humans;Hydrogen;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Neurologic Examination","Constans, J. M.;Meyerhoff, D. J.;Gerson, J.;MacKay, S.;Norman, D.;Fein, G.;Weiner, M. W.",1995,Nov,10.1148/radiology.197.2.7480705,0,
4859,Computed tomography of amyloid plaques in a mouse model of Alzheimer's disease using diffraction enhanced imaging,"Our understanding of early development in Alzheimer's disease (AD) is clouded by the scale at which the disease progresses; amyloid beta (Abeta) plaques, a hallmark feature of AD, are small (approximately 50 microm) and low contrast in diagnostic clinical imaging techniques. Diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique, has greater soft tissue contrast than conventional radiography and generates higher resolution images than magnetic resonance microimaging. Thus, in this proof of principle study, DEI in micro-CT mode was performed on the brains of AD-model mice to determine if DEI can visualize Abeta plaques. Results revealed small nodules in the cortex and hippocampus of the brain. Histology confirmed that the features seen in the DEI images of the brain were Abeta plaques. Several anatomical structures, including hippocampal subregions and white matter tracks, were also observed. Thus, DEI has strong promise in early diagnosis of AD, as well as general studies of the mouse brain.","Alzheimer Disease/pathology/ radiography;Animals;Brain/pathology/ radiography;Disease Models, Animal;Image Processing, Computer-Assisted;Immunohistochemistry;Mice;Mice, Transgenic;Plaque, Amyloid/pathology/ radiography;Tomography, X-Ray Computed/ methods","Connor, D. M.;Benveniste, H.;Dilmanian, F. A.;Kritzer, M. F.;Miller, L. M.;Zhong, Z.",2009,Jul 15,10.1016/j.neuroimage.2009.03.019,0,
4860,Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks,"Neuroimaging of older adults commonly reveals abnormality (leukoaraiosis) in the cerebral white matter. Studies have established that extensive leukoaraiosis predicts dementia and disability, but the pathogenesis of leukoaraiosis remains unclear. We recruited 5 patients with leukoaraiosis and performed magnetic resonance mapping of the brain for 16 consecutive weeks. We observed tiny lesions arising de novo in the cerebral white matter. These lesions were clinically silent. They had the signature features of acute ischemic stroke. With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis. Together, these findings suggest that tiny silent acute infarcts are a cause of leukoaraiosis.",Acute Disease;Aged;Brain Mapping/*trends;Cerebral Infarction/*complications/*diagnosis;Female;Humans;Leukoaraiosis/*diagnosis/*etiology;Magnetic Resonance Imaging/*trends;Male;Middle Aged;Prospective Studies;Risk Factors;Time Factors,"Conklin, J.;Silver, F. L.;Mikulis, D. J.;Mandell, D. M.",2014,Dec,10.1002/ana.24285,0,
4861,Incidence of radiation-induced leukoencephalopathy after whole brain radiotherapy in patients with brain metastases,"INTRODUCTION: Whole brain radiation therapy (WBRT) remains a recommended treatment for patients with brain metastases in terms of symptom palliation, especially when extracranial systemic disease is present. The aim of the study was to determine the clinical correlation between pre-existing leukoaraiosis and posterior leukoencephalopathy secondary to WBRT. METHODS AND MATERIALS: We retrospectively reviewed the results of WBRT treatment in 44 patients with melanoma brain metastases. The neuroimaging abnormalities of the white matter (T2-weighted MRI) were graded over time. RESULTS: From the 37 evaluable patients the mean age was 53 years old, 23 male and 14 female. Vascular risk factors were present in 22 patients (59.5%). The WBRT total dose was 20 Gy/5fr (n=21) and 30 Gy/10fr (n=16). Leukoaraiosis pre-WBRT was observed in 9/37 patients (24.3%) and leukoencephalopathy post-WBRT in 2/37 (5.4%). Univariate analysis of prognostic factors (sex, age and vascular risk factors) for leukoaraiosis was conducted observing statistically significant differences for patients with age>or=65 years old (p=0.003). Nineteen patients survived more than 3 months. Twelve patients (63.2%) suffered from vascular risk factors. Univariate analysis demonstrated previous leukoaraiosis as a prognostic factor for developing further leukoencephalopathy after WBRT (p=0.015). CONCLUSIONS: Radiation-induced leukoencephalopathy is greater in patients with pre-existing leukoaraiosis. Because of the potential of long-term survival in a small subset of patients with brain metastases and the risk of radiation-induced dementia, neurotoxicity reduction in patients with leukoaraiosis is an important goal of treatment.","Adolescent;Adult;Aged;Aged, 80 and over;Brain Neoplasms/complications/*radiotherapy/*secondary;Dose Fractionation;Female;Humans;Incidence;Leukoaraiosis/diagnosis;Male;Middle Aged;Posterior Leukoencephalopathy Syndrome/*epidemiology/etiology;Prognosis;Radiation Injuries/epidemiology;Radiotherapy/*adverse effects;Radiotherapy Dosage;Retrospective Studies;Treatment Outcome","Conill, C.;Berenguer, J.;Vargas, M.;Lopez-Soriano, A.;Valduvieco, I.;Marruecos, J.;Vilella, R.",2007,Sep,,0,
4862,Cerebral microbleeds on MR imaging: comparison between 1.5 and 7T,"BACKGROUND AND PURPOSE: The detection of microbleeds differs strongly between studies, due to differences in scan protocol. This study aims to compare the visualization of microbleeds with 3D T2*-weighted imaging at 1.5T with 3D dual-echo T2*-weighted imaging at 7T. MATERIALS AND METHODS: Thirty-four patients (29 male; mean age, 58 +/- 12 years) with atherosclerotic disease from the Second Manifestations of ARTerial Disease study were included. 3D T2*-weighted imaging at 1.5T and dual-echo T2*-weighted imaging at 7T were done in all patients. The presence and number of definite microbleeds were recorded on minimal intensity projections. Inter- and intraobserver reliability was assessed with Cohen kappa test and the ICC. The difference in presence and number of microbleeds was tested with the McNemar test and Wilcoxon signed rank test. RESULTS: The interobserver ICC at 7T was 0.61 and the intraobserver ICC was 0.94, whereas at 1.5T the interobserver ICC was 0.50 and the intraobserver ICC was 0.59. Microbleeds were detected in significantly more patients on 7T (50%) than on 1.5T scans (21%) (P = .001). The number of microbleeds was also higher at 7T (median, 0.5; range, 0-5) than on 1.5T (median, 0.0; range, 0-6) (P = .002). CONCLUSIONS: 3D dual-echo T2*-weighted imaging at 7T results in better and more reliable detection of microbleeds compared with 3D T2*-weighted imaging at 1.5T.",Alzheimer Disease/ complications/ diagnosis;Cerebral Hemorrhage/ diagnosis/ etiology;Female;Humans;Magnetic Resonance Angiography/ methods;Male;Middle Aged;Observer Variation;Reproducibility of Results;Sensitivity and Specificity,"Conijn, M. M.;Geerlings, M. I.;Biessels, G. J.;Takahara, T.;Witkamp, T. D.;Zwanenburg, J. J.;Luijten, P. R.;Hendrikse, J.",2011,Jun-Jul,10.3174/ajnr.A2450,0,
4863,MRI and localized proton MRS in early infantile form of neuronal ceroid- lipofuscinosis,A patient with early infantile neuronal ceroid-lipofuscinosis was examined by magnetic resonance imaging (MRI) and image-guided localized proton MR spectroscopy of brain using short-stimulated echo times. T(2)-weighted MRI revealed generalized cerebral atrophy and a reduction in signal intensity in thalamus and striatum associated with the presence of hyperintense white matter. The proton MR spectrum is characterized by an unusual increase of the inositol and taurine signals and by a reduction in the level of N-acetyl- aspartate contrasting with the presence of signals from glutamate-glutamine. The presence of a resonance from N-acetyl-methyl protons of N-acetyl- glucosamine (2.04 ppm) borne by dolichol is discussed.,,"Confort-Gouny, S.;Chabrol, B.;Vion-Dury, J.;Mancini, J.;Cozzone, P. J.",1993,1993,,0,
4864,Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation,"BACKGROUND: Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. METHODS: This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits. RESULTS: Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017. CONCLUSION: Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters.",,"Conen, D.;Rodondi, N.;Mueller, A.;Beer, J.;Auricchio, A.;Ammann, P.;Hayoz, D.;Kobza, R.;Moschovitis, G.;Shah, D.;Schlaepfer, J.;Novak, J.;di Valentino, M.;Erne, P.;Sticherling, C.;Bonati, L.;Ehret, G.;Roten, L.;Fischer, U.;Monsch, A.;Stippich, C.;Wuerfel, J.;Schwenkglenks, M.;Kuehne, M.;Osswald, S.",2017,Jul 11,,0,
4865,"White matter hyperintensities, cerebrospinal amyloid-β and dementia in Parkinson's disease","White-matter hyperintensities (WMHs) have been related to small-vessel disease, but also to amyloid-β (Αβ) vascular deposition, particularly in parieto-occipital regions. Low cerebrospinal fluid (CSF) Aβ [1-42] levels (biomarker of parenchymal and/or vascular Aβ deposition) and WMHs have been associated with Parkinson's disease (PD) and related dementia (PDD), separately but not in combination. We studied 50 subjects: 38 PD patients (19 non-demented [PDND] + 19 PDD) and 12 healthy-controls. Baseline regional WMHs from FLAIR MRI-sequences were dichotomized into none-to-mild vs. moderate-to-severe by an expert radiologist blind to clinical and CSF data using an adaption of the Age-Related White Matter Changes scale. Baseline CSF α-synuclein, τ and Aβ [1-42] levels were determined with ELISA techniques. Progression to dementia in PDND patients was clinically evaluated at 18 months. For analyses purposes patients were considered altogether (PDND + PDD) and separately (PDND vs. PDD). At baseline, moderate-to-severe parieto-occipital WMHs were significantly more frequent in PDD than in PDND (p = 0.049) and controls (p = 0.029), without significant differences in other regions. In regression models CSF Aβ was significantly associated in the entire PD cohort with moderate-to-severe parieto-occipital WMHs independently of age, vascular risk factors, APOE-4 and dementia. There were no associations with CSF α-synuclein and τ. Progression to dementia at 18 months was more frequent in patients with moderate-to-severe parieto-occipital WMHs and low CSF Aβ vs. those with none-to-mild parieto-occipital WMHs and normal CSF Aβ (p = 0.007). It remains to be seen whether the relationship between CSF Aβ and WMHs in PD and their association with PD-dementia is a reflection of not only parenchymal, but also vascular Αβ deposition.",alpha synuclein;amyloid beta protein[1-42];apolipoprotein A4;biological marker;age;age related white matter changes scale;aged;article;cerebrospinal fluid;Charlson Comorbidity Index;clinical article;cohort analysis;controlled study;cross-sectional study;dementia;disease severity;enzyme linked immunosorbent assay;female;human;male;Mini Mental State Examination;neurologic disease assessment;nuclear magnetic resonance imaging;Parkinson disease;priority journal;radiologist;risk factor;white matter hyperintensity;white matter lesion,"Compta, Y.;Buongiorno, M.;Bargalló, N.;Valldeoriola, F.;Muñoz, E.;Tolosa, E.;Ríos, J.;Cámara, A.;Fernández, M.;Martí, M. J.",2016,,,0,
4866,"White matter hyperintensities, cerebrospinal amyloid-beta and dementia in Parkinson's disease",,"0 (Amyloid beta-Peptides);0 (Apolipoproteins E);0 (Biomarkers);0 (Peptide Fragments);0 (SNCA protein, human);0 (alpha-Synuclein);0 (amyloid beta-protein (1-42));Aged;Amyloid beta-Peptides/ cerebrospinal fluid;Apolipoproteins E/genetics;Biomarkers/cerebrospinal fluid;Brain/diagnostic imaging;Case-Control Studies;Cross-Sectional Studies;Dementia/ cerebrospinal fluid/complications/ diagnostic imaging;Enzyme-Linked Immunosorbent Assay;Female;Follow-Up Studies;Humans;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Parkinson Disease/ cerebrospinal fluid/complications/ diagnostic;imaging/psychology;Peptide Fragments/ cerebrospinal fluid;Prospective Studies;Risk;White Matter/ diagnostic imaging;alpha-Synuclein/cerebrospinal fluid;Amyloid-beta;Cerebrospinal fluid;Dementia;Parkinson's disease;White matter hyperintensities","Compta, Y.;Buongiorno, M.;Bargallo, N.;Valldeoriola, F.;Munoz, E.;Tolosa, E.;Rios, J.;Camara, A.;Fernandez, M.;Marti, M. J.",2016,Aug 15,,0,
4867,Clinical and MRI assessment of brain damage in MS,"Cognitive impairment in multiple sclerosis (MS), generally in the form of the so-called subcortical dementia, results predominantly by the disruption of communication among cortical and subcortical areas, consequent to white matter damage. Studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by damage in the normal-appearing white matter (NAWM). This interpretation is supported by studies using non-conventional MRI techniques, more specific to the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.",,"Comi, G.;Rovaris, M.;Leocani, L.;Martinelli, V.;Filippi, M.",2001,2001,,0,
4868,Assessment of the damage of the cerebral hemispheres in MS using neuroimaging techniques,"The pattern of mental dysfunction in multiple sclerosis (MS) is characteristic of the so-called subcortical dementia. Cognitive dysfunction results predominantly by the disruption of communication among cortical and subcortical areas, as a consequence of the white matter damage. As expected, studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to the lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by the invisible damage in the normal-appearing white matter (NAWM). Recent studies using non-conventional MRI techniques with a higher specificity for the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM, support this interpretation. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role. Copyright (C) 2000 Elsevier Science B.V.",,"Comi, G.;Rovaris, M.;Leocani, L.;Martinelli, V.;Filippi, M.",2000,15,,0,
4869,Patterns of cerebellar volume loss in dementia with Lewy bodies and Alzheimers disease: A VBM-DARTEL study,"Evidence suggests that the cerebellum contributes to cognition as well as motor function. We investigated cerebellar grey matter (GM) and white matter (WM) changes from magnetic resonance images in dementia with Lewy bodies (DLB), Alzheimers disease (AD) and healthy older subjects using voxel-based morphometry (VBM). Subjects (39 controls, 41 DLB, and 48 AD) underwent magnetic resonance imaging as well as clinical and cognitive assessments. VBM used SPM8 with a cerebellar brain mask to define the subspace for voxel analysis. Statistical analyses were conducted using the general linear model. Relative to findings in controls, VBM analysis revealed cerebellar GM loss in lobule VI bilaterally in AD and in left Crus I and right Crus II regions in DLB. WM deficits were confined to AD in the bilateral middle cerebellar peduncles. DLB demonstrates a different pattern of cerebellar GM loss which, although not significantly different from that in AD, could be an important feature in understanding the neurobiology of DLB and warrants further investigation.","Aged;Alzheimer Disease/ pathology;Brain/pathology;Brain Mapping;Cerebellum/ pathology;Female;Humans;Image Interpretation, Computer-Assisted;Lewy Body Disease/ pathology;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size","Colloby, S. J.;O'Brien, J. T.;Taylor, J. P.",2014,Sep 30,10.1016/j.pscychresns.2014.06.006,0,
4870,Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease,"Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.",,"Colgan, N.;Siow, B.;O'Callaghan, J. M.;Harrison, I. F.;Wells, J. A.;Holmes, H. E.;Ismail, O.;Richardson, S.;Alexander, D. C.;Collins, E. C.;Fisher, E. M.;Johnson, R.;Schwarz, A. J.;Ahmed, Z.;O'Neill, M. J.;Murray, T. K.;Zhang, H.;Lythgoe, M. F.",2016,Jan 15,10.1016/j.neuroimage.2015.10.043,0,
4871,Status epilepticus and venous infarction in Sturge-Weber syndrome,Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that is typically associated with progressive neurological deterioration. We describe a 12-year-old girl with SWS who suffered a permanent cerebral insult as the result of a period of protracted status epilepticus. The case illustrates the unique susceptibility of patients with SWS to uncontrolled venous hypertension and emphasises the need for optimal seizure control and preservation of venous outflow. We discuss the relevance of our observations to haemodynamic concepts of neurological decline in SWS.,article;brain angiography;brain infarction;brain injury;brain vein;case report;computer assisted tomography;deterioration;epileptic state;female;hemodynamics;human;hypertension;nuclear magnetic resonance imaging;priority journal;school child;Sturge Weber syndrome,"Coley, S. C.;Britton, J.;Clarke, A.",1998,,,0,
4872,Folate homeostasis in cerebrospinal fluid during therapy for acute lymphoblastic leukemia,"The neurotoxic effects of therapy for childhood acute lymphoblastic leukemia can result in leukoencephalopathy or measurable deficits in cognitive function. However, there are no validated biomarkers that allow the identification of those patients at greatest risk. With the objective of identifying such predictors, cerebrospinal fluid collected from 53 patients over 2.5 years of therapy for childhood acute lymphoblastic leukemia was retrospectively studied. Cerebrospinal fluid folate, concentrated relative to serum folate prior to therapy, dropped during the first month of therapy and remained below baseline throughout treatment. Cerebrospinal fluid homocysteine was inversely related to cognitive function prior to treatment. Oral methotrexate was associated with decreased cerebrospinal fluid folate and increased cerebrospinal fluid homocysteine, but these changes were not seen with oral aminopterin. Of 36 patients who had imaging after completion of therapy, 9 had periventricular or subcortical white matter abnormalities consistent with leukoencephalopathy. Peak cerebrospinal fluid tau concentrations during therapy were higher among patients who had leukoencephalopathy after completion of therapy than among those with normal imaging studies at the end of therapy. If confirmed prospectively, these markers may allow the identification of those patients at greatest risk of developing treatment-induced neurocognitive dysfunction, thus guiding preventive interventions.","Administration, Oral;Adolescent;Aminopterin/adverse effects;Antineoplastic Combined Chemotherapy Protocols/administration & dosage/ adverse;effects;Biomarkers, Tumor/blood/ cerebrospinal fluid;Brain/pathology;Child;Child, Preschool;Chromatography, High Pressure Liquid;Cognition/ drug effects;Dementia, Vascular/etiology/pathology/physiopathology;Folic Acid/blood/ cerebrospinal fluid;Folic Acid Antagonists/adverse effects;Homeostasis;Homocysteine/cerebrospinal fluid;Humans;Infant;Magnetic Resonance Imaging;Methotrexate/adverse effects;Neurotoxicity Syndromes/etiology/pathology/physiopathology;Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood/ cerebrospinal fluid/ drug;therapy;Retrospective Studies;Young Adult;tau Proteins/cerebrospinal fluid","Cole, P. D.;Beckwith, K. A.;Vijayanathan, V.;Roychowdhury, S.;Smith, A. K.;Kamen, B. A.",2009,Jan,10.1016/j.pediatrneurol.2008.09.005,0,
4873,Prediction of brain age suggests accelerated atrophy after traumatic brain injury,"Objective The long-term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging model that predicts brain age in healthy individuals and then apply it to TBI patients. We define individuals' differences in chronological and predicted structural «brain age,» and test whether TBI produces progressive atrophy and how this relates to cognitive function. Methods A predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging-derived estimates of gray matter (GM) and white matter (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age. Results The initial model accurately predicted age in healthy individuals (r=0.92). TBI brains were estimated to be «older,» with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (±10.8) for GM and 5.97 years (±11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase. Interpretation TBI patients' brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age-associated conditions, motivating further research into the age-like effects of brain injury and other neurological diseases. Ann Neurol 2015;77:571-581",,"Cole, J. H.;Leech, R.;Sharp, D. J.",2015,1,,0,
4874,"Progressive myoclonic encephalopathy in X-linked hypogamma-globulinemia. Case report, review of the literature and its relationship with progressive encephalopathy in children with AIDS","A 7-year-old boy suffering from X-linked hypogammaglobulinemia and progressive myoclonic encephalopathy is reported. The onset of neurological disturbances is at four years of age with ataxic gait and myoclonic jerks. The EEG shows a progressive slowing of background activity, bilateral diffuse and repetitive, pseudoperiodic, high amplitude slow waves, myoclonic jerks polygraphically documented. The CT-scan shows generalized cerebral atrophy, white matter hypodensity (principally in the frontal regions), multiple nodular calcifications, also in the basal ganglia. Two years after the onset of neurological signs, the boy is completely bedridden, spastic, dement and blind; the myoclonic jerks persist. Finally the relationship is discussed with both the previously reported patients with the same affection, and with similar progressive encephalopathy in children suffering from AIDS.",acquired immune deficiency syndrome;ataxia;brain atrophy;brain calcification;brain disease;case report;computer analysis;computer assisted tomography;disease association;electroencephalography;heredity;human;immunoglobulin deficiency;male;myoclonus;preschool child;priority journal;X chromosomal inheritance,"Colamaria, V.;Marradi, P.;Boner, A.;Pajno-Ferrara, F.;Procacci, C.;Cesaro, G.;La Selva, L.;Capovilla, G.;Fontana, E.;Dalla Bernardina, B.",1989,,,0,
4875,Change in brain and lesion volumes after CEE therapies: The WHIMS-MRI studies,"Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixedeffect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Results: Total brain volume decreased an average of 3.22 cm3/y in the active arm and 3.07 cm3/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm3/y (p = 0.88). Conclusions: Conjugated equine estrogen-based postmenopausal HT, previously assigned atWHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.",NCT00000611;conjugated estrogen;medroxyprogesterone acetate;placebo;aged;article;basal ganglion;brain atrophy;brain damage;brain ischemia;brain size;cardiovascular disease;cerebrovascular accident;controlled study;dementia;female;follow up;frontal lobe;gray matter;hormonal therapy;human;major clinical study;mild cognitive impairment;nuclear magnetic resonance imaging;outcome assessment;priority journal;randomized controlled trial;treatment duration;very elderly;white matter lesion,"Coker, L. H.;Espeland, M. A.;Hogan, P. E.;Resnick, S. M.;Bryan, R. N.;Robinson, J. G.;Goveas, J. S.;Davatzikos, C.;Kuller, L. H.;Williamson, J. D.;Bushnell, C. D.;Shumaker, S. A.",2014,,10.1212/wnl.0000000000000079,0,4876
4876,Change in brain and lesion volumes after CEE therapies: the WHIMS-MRI studies,"OBJECTIVES: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. METHODS: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. RESULTS: Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88). CONCLUSIONS: Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.","Brain [drug effects] [pathology];Estrogen Replacement Therapy [adverse effects] [methods] [trends];Estrogens, Conjugated (USP) [administration & dosage] [adverse effects];Longitudinal Studies;Magnetic Resonance Imaging [trends];Organ Size;Women's Health [trends];Aged[checkword];Female[checkword];Humans[checkword];Middle Aged[checkword];aged;article;basal ganglion;brain atrophy;brain damage;brain ischemia;brain size;cardiovascular disease;cerebrovascular accident;controlled study;dementia;female;follow up;frontal lobe;gray matter;hormonal therapy;human;major clinical study;mild cognitive impairment;nuclear magnetic resonance imaging;outcome assessment;priority journal;randomized controlled trial;treatment duration;very elderly;white matter lesion;conjugated estrogen;medroxyprogesterone acetate;placebo","Coker, L. H.;Espeland, M. A.;Hogan, P. E.;Resnick, S. M.;Bryan, R. N.;Robinson, J. G.;Goveas, J. S.;Davatzikos, C.;Kuller, L. H.;Williamson, J. D.;Bushnell, C. D.;Shumaker, S. A.",2014,,10.1212/wnl.0000000000000079,0,
4877,The relationship of subcortical MRI hyperintensities and brain volume to cognitive function in vascular dementia,"The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 ± 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive-psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive-psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD.",,"Cohen, R. A.;Paul, R. H.;Ott, B. R.;Moser, D. J.;Zawacki, T. M.;Stone, W.;Gordon, N.",2002,September,,0,
4878,Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes,"Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.",Adult;Basal Ganglia/pathology/virology;Cerebral Cortex/ pathology/virology;Cohort Studies;Female;Frontal Lobe/pathology/virology;HIV/pathogenicity;HIV Infections/ metabolism/ pathology;Humans;Linear Models;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Multicenter Studies as Topic;Neuroglia/metabolism;Thalamus/pathology/virology,"Cohen, R. A.;Harezlak, J.;Gongvatana, A.;Buchthal, S.;Schifitto, G.;Clark, U.;Paul, R.;Taylor, M.;Thompson, P.;Tate, D.;Alger, J.;Brown, M.;Zhong, J.;Campbell, T.;Singer, E.;Daar, E.;McMahon, D.;Tso, Y.;Yiannoutsos, C. T.;Navia, B.",2010,Nov,10.3109/13550284.2010.520817,0,
4879,Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP,Tomographic imaging of the brain was performed using a rotating slant hole collimator and [(123)I]N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n=6) and patients with either Alzheimer's disease (n=5) or multiple infarct dementia (n=3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of (123)I appears to be a useful technique for the evaluation of demented patients.,,"Cohen, M. B.;Graham, L. S.;Lake, R.",1986,1986,,0,
4880,Amyloidoma of the CNS. I. Clinical and pathologic study,"We report a 32-year-old man with a 4-year history of headaches, seizures, and dementia secondary to multifocal amyloidomas in the white matter. Immunohistochemical and electron microscopic analyses suggest that the amyloidomas resulted from processing of plasma-cell-derived amyloidogenic protein by microglial cells.",amyloid protein;adult;amyloidosis;article;case report;clinical feature;dementia;electron microscopy;headache;histopathology;human;immunohistochemistry;male;microglia;nuclear magnetic resonance imaging;plasma cell;priority journal;seizure;white matter,"Cohen, M.;Lanska, D.;Roessmann, U.;Karaman, B.;Ganz, E.;Whitehouse, P.;Gambetti, P.",1992,,,0,
4881,Humanin Derivatives Inhibit Necrotic Cell Death in Neurons,"Humanin and its derivatives are peptides known for their protective antiapoptotic effects against Alzheimer's disease. Herein, we identify a novel function of the humanin-derivative AGA(C8R)-HNG17 (namely, protection against cellular necrosis). Necrosis is one of the main modes of cell death, which was until recently considered an unmoderated process. However, recent findings suggest the opposite. We have found that AGA(C8R)-HNG17 confers protection against necrosis in the neuronal cell lines PC-12 and NSC-34, where necrosis is induced in a glucose-free medium by either chemohypoxia or by a shift from apoptosis to necrosis. Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect. This result is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema, as measured by magnetic resonance imaging (MRI). An insight into the peptide's antinecrotic mechanism was attained through measurements of cellular ATP levels in PC-12 cells under necrotic conditions, showing that the peptide mitigates a necrosis-associated decrease in ATP levels. Further, we demonstrate the peptide's direct enhancement of the activity of ATP synthase activity, isolated from rat-liver mitochondria, suggesting that AGA(C8R)-HNG17 targets the mitochondria and regulates cellular ATP levels. Thus, AGA(C8R)-HNG17 has potential use for the development of drug therapies for necrosis-related diseases, for example, traumatic brain injury, stroke, myocardial infarction, and other conditions for which no efficient drug-based treatment is currently available. Finally, this study provides new insight into the mechanisms underlying the antinecrotic mode of action of AGA(C8R)-HNG17.",,"Cohen, A.;Lerner-Yardeni, J.;Meridor, D.;Kasher, R.;Nathan, I.;Parola, A. H.",2015,,10.2119/molmed.2015.00073,0,
4882,"Response to letter regarding article, ""archetypal Arg169Cys Mutation in NOTCH3 Does Not Drive the Pathogenesis in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy via a Loss-of-Function Mechanism""",,cysteine;epidermal growth factor;Notch3 receptor;CADASIL;cerebrovascular accident;cerebrovascular disease;gene deletion;gene frequency;gene insertion;human;in vivo study;letter;loss of function mutation;migraine with aura;neurologic examination;nonsense mutation;nuclear magnetic resonance imaging;parkinsonism;pathogenicity;polyneuropathy;priority journal,"Cognat, E.;Hervé, D.;Joutel, A.",2014,,,0,
4883,Leukoaraiosis in asymptomatic adult offspring of individuals with Alzheimer's disease,"The presence of white matter changes on magnetic resonance imaging (MRI), which has been referred to by Hachinski (1987) as leukoaraiosis, is frequently noted in elderly individuals in conditions ranging from health to frank dementia. This study involved the use of MRI to document cerebral structure if 41 healthy 50-60-year-old individuals, 28 of whom were offspring of Alzheimer's disease victims. On visual inspection of spin-echo images, 13 of the 28 offspring showed white matter lesions whereas all of the controls were free of leukoaraiosis. This statistically significant difference suggests that the presence of leukoaraiosis might be of importance in understanding changes in the white matter among populations at increased risk for Alzheimer's disease.","Alzheimer Disease/diagnosis/ genetics;Brain/ pathology;Brain Damage, Chronic/diagnosis/ genetics;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors","Coffman, J. A.;Torello, M. W.;Bornstein, R. A.;Chakeres, D.;Burns, E.;Nasrallah, H. A.",1990,Jun 1,,0,
4884,Can the Treatment of Hypertension in the Middle-Aged Prevent Dementia in the Elderly?,"Hypertension, one of the main risk factors for cardiovascular disease, is thought to play a crucial role in the pathophysiology of cognitive impairment. Studies have associated hypertension with subjective cognitive failures and objective cognitive decline. Subjective cognitive failures may reflect the early phase of a long pathological process leading to cognitive decline and dementia that has been associated with hypertension and other cardiovascular risk factors. The underlying cerebral structural change associated with cognitive decline may be a consequence of the cerebral small-vessel disease induced by high blood pressure and may be detected on magnetic resonance imaging as white matter hyperintensities, cerebral microbleeds, lacunar infarcts or enlarged perivascular spaces. The increasing interest in the relationship between hypertension and cognitive decline is based on the fact that blood pressure control in middle-aged subjects may delay or stop the progression of cognitive decline and reduce the risk of dementia in the elderly. Although more evidence is required, several studies on hypertension have shown a beneficial effect on the incidence of dementia.",antihypertensive agent;Alzheimer disease;antihypertensive therapy;article;brain hemorrhage;cardiovascular risk;cerebrovascular disease;cognition;dementia;depersonalization;disorientation;human;hypertension;incidence;lacunar stroke;mental deterioration;mild cognitive impairment;multiinfarct dementia;nuclear magnetic resonance imaging;onset age;pathophysiology;perivascular space;priority journal;risk assessment;white matter,"Coca, A.;Monteagudo, E.;Doménech, M.;Camafort, M.;Sierra, C.",2016,,10.1007/s40292-016-0144-5,0,
4885,Can the Treatment of Hypertension in the Middle-Aged Prevent Dementia in the Elderly?,"Hypertension, one of the main risk factors for cardiovascular disease, is thought to play a crucial role in the pathophysiology of cognitive impairment. Studies have associated hypertension with subjective cognitive failures and objective cognitive decline. Subjective cognitive failures may reflect the early phase of a long pathological process leading to cognitive decline and dementia that has been associated with hypertension and other cardiovascular risk factors. The underlying cerebral structural change associated with cognitive decline may be a consequence of the cerebral small-vessel disease induced by high blood pressure and may be detected on magnetic resonance imaging as white matter hyperintensities, cerebral microbleeds, lacunar infarcts or enlarged perivascular spaces. The increasing interest in the relationship between hypertension and cognitive decline is based on the fact that blood pressure control in middle-aged subjects may delay or stop the progression of cognitive decline and reduce the risk of dementia in the elderly. Although more evidence is required, several studies on hypertension have shown a beneficial effect on the incidence of dementia.",,"Coca, A.;Monteagudo, E.;Domenech, M.;Camafort, M.;Sierra, C.",2016,Apr 13,10.1007/s40292-016-0144-5,0,
4886,Molecular Disorganization of Axons Adjacent to Human Cortical Microinfarcts,"Cortical microinfarcts (CMIs) are microscopically identified wedge-shaped ischemic lesions that occur at or near the cortical surface and result from occlusion of penetrating arterioles. These microscopic lesions can be observed with high-resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease. Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer's disease as well as other forms of dementia. We have recently shown that the molecular organization of axons into functional microdomains is altered in areas adjacent to white matter lacunar and microinfarcts, creating a peri-infarct penumbral injury in surviving axons. Whether similar changes in nodal, adjacent paranodal, and proximal axon initial segment molecular organization occur in the cortex adjacent to human CMIs is not known. Paraffin-embedded sections of autopsy brain tissue from five patients with CMIs were immunofluorescently labeled for nodal and paranodal markers including beta-IV spectrin, ankyrin-G, and contactin-associated protein. High magnification images from the peri-infarct cortical tissue were generated using confocal microscopy. In surviving cortical tissue adjacent to microinfarcts, we observed a dramatic loss of axon initial segments, suggesting that neuronal firing capacity in adjacent cortical tissue is likely compromised. The number of identifiable nodal/paranodal complexes in surviving cortical tissue is reduced adjacent to microinfarcts, while the average paranodal length is increased indicating a breakdown of axoglial contact. This axonal microdomain disorganization occurs in the relative absence of changes in the structural integrity of myelinated axons as measured by myelin basic protein and neurofilament staining. These findings indicate that the molecular organization of surviving axons adjacent to human CMIs is abnormal, reflecting lost axoglial contact and the functional elements necessary for neural transmission. This study provides support for the concept of a microinfarct penumbral injury that may account for the cumulative cognitive effect of these tiny strokes.",cortical microinfarct;microinfarct;neuropathology;small vessel disease;vascular dementia,"Coban, H.;Tung, S.;Yoo, B.;Vinters, H. V.;Hinman, J. D.",2017,,,0,
4887,Where (in the brain) do semantic errors come from?,Background: Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone. Methods: A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits. Results: Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37. Conclusion: Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions. © 2008 Elsevier Srl. All rights reserved.,,"Cloutman, L.;Gottesman, R.;Chaudhry, P.;Davis, C.;Kleinman, J. T.;Pawlak, M.;Herskovits, E. H.;Kannan, V.;Lee, A.;Newhart, M.;Heidler-Gary, J.;Hillis, A. E.",2009,May,,0,
4888,Genetically confirmed CADASIL in a pediatric patient,"A 17-year-old girl presented with migraine with prolonged aura and aura without headache. Neurologic examination was normal. Her mother, who did not have a history of migraine, developed right-face and -arm numbness at the age of 45. Evaluation revealed white matter changes consistent with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and genetic testing showed a Notch3 gene mutation consistent with CADASIL. Our patient's MRI revealed white matter changes and the same Notch3 gene mutation. Low-dose aspirin was started in an attempt to prevent stroke. CADASIL is considered a degenerative disease of adult onset that leads to progressive neurologic deterioration. Onset of symptoms is in the third decade. Migraine, one of its most common manifestations, can develop in childhood. Evaluation for secondary causes is warranted in select pediatric patients who present with atypical migraine, when there is a family history of CADASIL or atypical patterns such as aura without headache, or in the presence of white matter abnormalities. The pathophysiology of CADASIL is poorly understood, and there is no proven effective therapy. Patients require genetic counseling and close follow-up. It is not known if interventions such as antiplatelet therapy are beneficial if instituted early in the course of the disease. Screening of family members at risk for CADASIL, even in the pediatric population, should be considered and offered to patients with CADASIL and their families. CADASIL has rarely been described in the pediatric population. This case report expands our current understanding of the disorder in children. Copyright © 2010 by the American Academy of Pediatrics.",acetylsalicylic acid;nonsteroid antiinflammatory agent;Notch3 receptor;topiramate;adolescent;amino acid substitution;anamnesis;article;CADASIL;case report;female;gene mutation;genetic screening;headache;human;migraine;nuclear magnetic resonance imaging;priority journal;cerebrovascular accident;white matter;aspirin,"Cleves, C.;Friedman, N. R.;Rothner, A. D.;Hussain, M. S.",2010,,,0,
4889,Can FreeSurfer Compete with Manual Volumetric Measurements in Alzheimer's Disease?,"Alzheimer's disease-related pathology results in tremendous structural and functional changes in the brain. These morphological changes might lead to a less precise performance of automated brain segmentation techniques in AD-patients, which in turn could possibly lead to false allocations of gray matter, white matter or cerebrospinal fluid. FreeSurfer has been shown to operate as an accurate and reliable instrument to measure cortical thickness and volume of neuroanatomical structures. Considering the principal role of FreeSurfer in the imaging field of AD, the present study aims to investigate the robustness of FreeSurfer to capture morphological changes in the brain against varying processing variables in comparison to manual measurements (the gold standard). T1-weighted MRI scan data were used pertaining to a sample of 53 individuals (18 healthy participants, 18 patients with mild cognitive impairment, and 18 patients with mild AD). Data were analyzed with different FreeSurfer versions (v4.3.1, v4.5.0, v5.0.0, v5.1.0), on a custom-built cluster (LINUX) and a Macintosh (UNIX) workstation. Group differences across versions and workstations were most consistent for both the hippocampus and posterior cingulate, regions known to be affected in the earliest stages of the disease. The results showed that later versions of FreeSurfer were more sensitive to identify group differences and corresponded best with the results of gold standard manual volumetric methods. In conclusion, later versions of FreeSurfer were more accurate than earlier versions, especially in medial temporal and posterior parietal regions. This development is very promising for future applications of FreeSurfer in research studies and encourages the future role of FreeSurfer output as a candidate marker in clinical practice.","Aged;Alzheimer Disease/ pathology;Brain/ pathology;Humans;Image Processing, Computer-Assisted/ methods;Male;Middle Aged;Mild Cognitive Impairment/ pathology;Organ Size;Pattern Recognition, Automated/ methods;Software","Clerx, L.;Gronenschild, E. H.;Echavarri, C.;Verhey, F.;Aalten, P.;Jacobs, H. I.",2015,,,0,
4890,"Low Prevalence of Mixed Dementia in a Cohort of 2,000 Elderly Patients in a Memory Clinic Setting","BACKGROUND: It is generally assumed that with increasing age, pathology in clinically diagnosed Alzheimer's disease (AD) becomes more mixed, i.e., co-existence of amyloid plaques and cerebrovascular pathology. OBJECTIVE: To test the hypothesis of increasing prevalence of mixed dementia in late-onset clinically diagnosed Alzheimer's disease (AD) in a single-center memory clinic population. METHODS: Patients included had diagnoses of AD (n = 832), subjective cognitive impairment (SCI, n = 333), mild cognitive impairment (MCI, n = 492), vascular dementia (VaD, n = 57), other dementia (n = 53), or other diagnosis (n = 233). Prevalence of severe white matter lesions (WML) was defined as a score of 2 or higher on the Fazekas-scale on brain computed tomography to classify AD patients as having mixed dementia. We examined the effect of age on WML using multiple linear regression analysis, and AD patients were compared to SCI to determine the effect of disease on WML. RESULTS: Prevalence of severe WML was 33.6% in AD patients (mixed dementia), 11.4% in SCI, 22.7% in MCI, 75.4% in VaD, 3.8% in other dementia, and 15.5% in other diagnosis. With increasing age there was a significant and similar increase of WML scores in SCI, MCI, AD, other dementia, and other diagnosis, indicating no effect modification by AD. The difference between AD patients and SCI averaged 0.16 on the WML score and difference in percentage severe WML between AD and SCI patients was 15% across all ages. CONCLUSION: We found a low prevalence of mixed dementia. Furthermore, severe WML in AD was largely explained by age rather than effect of disease.",Alzheimer's disease;Fazekas score;computed tomography;memory clinic;white matter lesions,"Claus, J. J.;Staekenborg, S. S.;Roorda, J. J.;Stevens, M.;Herderschee, D.;van Maarschalkerweerd, W.;Schuurmans, L.;Tielkes, C. E.;Koster, P.;Bavinck, C.;Scheltens, P.",2016,Jan 6,10.3233/jad-150796,0,
4891,Magnetic resonance imaging correlates of depression in early- and late-onset Alzheimer's disease,"BACKGROUND: Depressive symptoms are frequent complications of Alzheimer's disease (AD). We hypothesized that AD patients with depression would be more likely than nondepressed AD patients to show deep white-matter, subcortical gray-matter, and periventricular hyperintensities on magnetic resonance imaging (MRI). METHODS: In a retrospective study of 31 AD patients, depression was characterized by clinical diagnosis (DSM-III-R major depression, depressive symptoms, or no depression), a clinician-rated depression scale, and informant ratings of premorbid (before memory disorder) as well as current depression using the NEO Personality Inventory (NEO-PI), and related to qualitative and quantitative ratings of MRI hyperintensities. RESULTS: In contrast to reports in nondemented elderly patients, there was no relationship between clinical diagnosis of major depressive episode and hyperintensities; however, clinician-rated depressive symptoms were higher in subjects with large anterior hyperintensities. In the early-onset AD group only, MRI abnormalities were related to greater premorbid depression, and less increase in depression after the onset of dementia, as rated by informants on the NEO-PI. CONCLUSIONS: Results highlight the need to consider early- and late-onset AD separately when assessing relationships between personality and MRI abnormalities, and to consider premorbid personality style when drawing conclusions about the etiology of depressive features seen in AD.",Age of Onset;Aged;Alzheimer Disease/ pathology/psychology;Brain/ pathology;Depressive Disorder/ pathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Psychiatric Status Rating Scales,"Clark, L. M.;McDonald, W. M.;Welsh-Bohmer, K. A.;Siegler, I. C.;Dawson, D. V.;Tupler, L. A.;Krishnan, K. R.",1998,Oct 1,,0,
4892,Chorea and rapidly progressive subcortical dementia in antiphospholipid syndrome,"Antiphospholipid antibodies are associated with a variety of neurologic manifestations, both in patients with and without concomitant systemic lupus erythematosus. We report a patient in whom chorea and rapidly progressive subcortical dementia developed in the setting of persistently high titers of antiphospholipid antibodies. While some manifestations of antiphospholipid syndrome can be clearly linked to vascular thrombosis, it is not known whether this is also true for patients affected with chorea, dementia, or both. In our patient, serial magnetic resonance imaging showed the progressive development of deep white matter lesions but no cortical infarcts. The development of widespread pulmonary arterial thrombosis and acute cerebral ischemia, evidenced clinically and on diffusion-weighted magnetic resonance imaging of the brain, provided indirect evidence for a thrombotic pathogenesis for this patient's neurologic disease. Anticoagulation should be considered as an adjunct to the treatment of patients with antiphospholipid antibodies and chorea or subcortical dementia.",,"Ciubotaru, C. R.;Esfahani, F.;Benedict, R. H.;Wild, L. M.;Baer, A. N.",2002,Dec,,0,
4893,An unusual neurological feature of HIV-1 encephalopathy: Gerstmann's syndrome,"The authors describe the first case in literature of Gerstmann's syndrome (agraphia, acalculia, finger agnosia) occurred in HIV correlated encephalopathy developed as the first severe manifestation of HIV infection in a patient with prevalent white matter neuroradiologic alterations. The PDL rapidly extended from the left subcortical parietal-occipital regions to the pre-rolandic one, with subsequent involvement of the corpus calosum splenium and the bilateral temporal lobes white matter. The authors indicate the extent of the lesions and the involvement of the interhemispheric connection fibres as the pathogenetic mechanism of the ""Gerstmann syndrome"", that until today has not been reported in the literature of the wide variety of AIDS dementia complex. The administration of 1 g of zidovudine for about 9 months did not avoid the establishing of the neurologic damage, but the sudden suspension of the drug could have enhanced the exacerbation of inflammation and the involvement of areas whose lesion is classically believed responsible for cognitive impairment.",azathioprine;acquired immune deficiency syndrome;adult;article;brain cortex;case report;drug effect;Gerstmann syndrome;hemispheric dominance;homosexuality;human;Human immunodeficiency virus 1;male;neuropsychological test;nuclear magnetic resonance imaging;pathology;physiology;psychological aspect,"Cirelli, A.;Ciardi, M.;Salotti, A.;Rossi, F.",1994,,,0,
4894,Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy in acromegalic patient with severe headache,"A 68-year-old female patient was admitted in our clinic with severe frontal bilateral headache, dizziness, depression and cognitive decline in the context of a previously diagnosed acromegaly. She also had high blood pressure, dyslipidemia, secondary diabetes mellitus. Acromegaly was caused by a growth hormone (GH) secreting-pituitary macroadenoma, so a transsphenoidal surgery was performed. The postoperative magnetic resonance imaging (MRI) scan revealed a 20÷22÷25 mm pituitary mass remnant and medical therapy with somatostatin analogues (SSAs) was started. After nine months of treatment with SSAs, she continued having severe headache, the blood pressure was well controlled, but GH secretion was only partially controlled with insulin-like growth factor-1 (IGF-1) level still above the normal value. The MRI scan showed the same pituitary tumor remnant with supra- and parasellar right extension and also multiple fronto-temporo-parietal subcortical lesions that could suggest in the clinical context cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). According to a pregenetic screening tool, the Pescini Scale, the patient had a 19 points score, which is highly suggestive for CADASIL, an inherited cerebrovascular disease due to mutations of the Notch3 gene at the chromosome locus 19p13. In the absence of genetic testing, an alternate way to prove small vessels disease, the skin biopsy, was performed. Electron microscopy showed granular osmiophilic material (GOM) surrounding the vascular smooth muscle cells on that are pathognomonic for the disease. Our report underscores the importance of repeated investigations even in patients with apparently obvious explanations of their condition since they may have multiple diseases with the same presenting clinical signs.",acromegaly;aged;CADASIL;case report;female;headache;human;pathology,"Cima, L. N.;Fica, S. V.;Albu, A. I.;Lambrescu, I. M.;Lăcău, I. S.;Popescu, B. O.;Gherghiceanu, M.;Badiu, C. V.;Barbu, C. G.",2016,,,0,
4895,Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington's disease,"We studied the anatomic and functional changes in various brain areas during the course of Huntington's disease (HD) in a large cohort of mutation-positive individuals (n = 71) encompassing the complete range of disability (presymptomatic through stage V), and in healthy controls, for the purpose of defining both degenerative and dysfunctional brain changes in the same subjects. METHODS: We used an MRI and unsupervised multiparametric segmentation procedure based on a relaxometric approach to measure in vivo brain volumes in 71 subjects with presymptomatic to advanced HD. The same population was evaluated by 18F-FDG PET to assess variations in brain glucose metabolism. To predict age at onset in unaffected mutation carriers, we considered the estimated number of years from each subject's age to manifested HD symptoms, for a given expanded triplet number. RESULTS: Age-adjusted analyses confirmed that the 71 subjects as a group, as well as the subgroup of 24 unaffected presymptomatic subjects at risk for HD, had significantly smaller gray-matter and white-matter volumes and larger cerebrospinal fluid volumes than did controls (P < 0.0001). In the 24 presymptomatic subjects, we observed a significant inverse linear correlation between white-matter volume reduction and the estimated time to symptom onset (r2= 0.39; P = 0.0011). Both clinically unaffected subjects at risk for HD and symptomatic patients had significantly decreased glucose uptake in the cortex (frontal and temporal lobes) and striatum (caudate and putamen). HD subjects who were followed up longitudinally showed progressive white-matter reduction in the preclinical subjects (n = 10) and decreased glucose uptake in the cortex and striatum in affected (n = 21) and preclinical (n = 10) subjects. CONCLUSION: White-matter volume loss may precede gray-matter atrophy and may be associated with neuronal dysfunction in early disease.","Adult;Atrophy/diagnosis;Brain/metabolism/*pathology/*radionuclide imaging;Cohort Studies;Female;Fluorodeoxyglucose F18;Glucose Metabolism Disorders/*diagnosis;Humans;Huntington Disease/*diagnosis;Image Interpretation, Computer-Assisted/methods;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology/*radionuclide imaging;Positron-Emission Tomography/methods;Prognosis;Radiopharmaceuticals;Reproducibility of Results;Risk Assessment/methods;Sensitivity and Specificity","Ciarmiello, A.;Cannella, M.;Lastoria, S.;Simonelli, M.;Frati, L.;Rubinsztein, D. C.;Squitieri, F.",2006,Feb,,0,
4896,White matter disease as a biomarker for long-term cerebrovascular disease and dementia topical collection on cerebrovascular disease and stroke,,article;basal ganglion;brain ischemia;central nervous system disease;cerebrovascular disease;cognitive defect;computer assisted tomography;dementia;diagnostic accuracy;diagnostic value;disease severity;executive function;heart infarction;hematoma;high risk population;human;lacunar stroke;leukoaraiosis;mortality;nuclear magnetic resonance imaging;rating scale;white matter;white matter hyperintensity;white matter lesion,"Chutinet, A.;Rost, N. S.",2014,,,0,
4897,White matter disease as a biomarker for long-term cerebrovascular disease and dementia,"OPINION STATEMENT: White matter disease is commonly detected on brain MRI of aging individuals as white matter hyperintensities (WMH), or 'leukoaraiosis."" Over the years, it has become increasingly clear that the presence and extent of WMH is a radiographic marker of small cerebral vessel disease and an important predictor of the lifelong risk of stroke, cognitive impairment, and functional disability. A number of large population-based studies have outlined the significance of WMH as a biomarker for long-term cerebrovascular disease and dementia. In this review, we describe the conceptual framework and methodology that support this association and link the existing knowledge to future lines of investigation in the field.",,"Chutinet, A.;Rost, N. S.",2014,Mar,10.1007/s11936-013-0292-z,0,
4898,A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patient presenting with chorea,"In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), clinical presentation with movement disorders such as dystonia and progressive supranuclear palsy-phenotype are rarely reported. None of the CADASIL cases, to our knowledge, has been reported with chorea. Herein, we describe a Korean woman with CADASIL who had presented with chorea. 18F-fl uorodeoxyglucose positron emission tomography (FDG-PET) showed hypometabolism in the right basal ganglia. We found decreased FDG uptake of the right basal ganglia by SPM analysis.",fluorodeoxyglucose f 18;adult;article;basal ganglion;brain ischemia;CADASIL;case report;chorea;cognitive defect;depression;dyskinesia;ethnic group;female;headache;human;Korean;medical history;neurologic examination;nuclear magnetic resonance imaging;positron emission tomography,"Chung, E. J.;Kim, S. J.",2012,,,0,
4899,More severe white matter changes in the elderly with jugular venous reflux,"OBJECTIVE: The etiology of age-related white matter changes is unclear. Cerebral white matter changes on magnetic resonance imaging (MRI) and progressive dementia have been reported in patients with dural arteriovenous fistulas of the sigmoid sinus. The frequency of jugular venous reflux, which mimics a dural arteriovenous fistula, significantly increases with age. We investigated whether jugular venous reflux was associated with the severity of age-related white matter changes in 97 persons (aged 55-90 years, mean [standard deviation]: 75.77 [8.19] years; 55 men) from a medical center memory clinic. METHODS: MRI (1.5T) and the semiquantitative Scheltens scale were used to investigate the severity of white matter changes. Subjects were classified into 3 groups (no, mild, and severe jugular venous reflux) by duplex ultrasonography. RESULTS: Subjects with severe jugular venous reflux had more severe age-related white matter changes in occipital subcortical, thalamus, pontine, and summed infratentorial regions compared with subjects with no jugular venous reflux (all corrected p < 0.0166), especially subjects aged >/=75 years (corrected p < 0.0166 in occipital subcortical; corrected p < 0.0001 in pontine and summed infratentorial regions). In subjects >/=75 years, we further noted that the whole brain age-related white matter changes rating scores were higher in the severe jugular venous reflux group than the no and mild jugular venous reflux groups (corrected p < 0.0166). INTERPRETATION: People with severe jugular venous reflux exhibit more severe age-related white matter changes, especially in caudal brain regions. We also demonstrate age-dependent jugular venous reflux effects on the severity of age-related white matter changes. These findings may provide new clues into the pathophysiology of age-related white matter changes.","Age Factors;Aged;Aged, 80 and over;Brain/ pathology;Female;Humans;Jugular Veins/physiopathology/ ultrasonography;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Severity of Illness Index;Statistics, Nonparametric","Chung, C. P.;Wang, P. N.;Wu, Y. H.;Tsao, Y. C.;Sheng, W. Y.;Lin, K. N.;Lin, S. J.;Hu, H. H.",2011,Mar,10.1002/ana.22276,0,
4900,Pathogenesis of leukoaraiosis: Role of jugular venous reflux,"Leukoaraiosis (LA) is a major cause of vascular dementia and disability in the elderly. Age and hypertension are the most two important risk factors. Despite its clinical significance, the etiology is so far unclear. Chronic cerebral hypoperfusion associated with vasogenic edema, microbleeding or/and endothelial dysfunction found in LA favors venous ischemia, in stead of arterial ischemia, as its pathogenesis. The involved regions in LA, periventricular and subcortical regions, are the drainage territory of deep cerebral venous system and the watershed region between the superficial and deep cerebral venous system respectively. Adding the facts that periventricular venule collagenosis, and retinal and intraparenchymal venules dilatation are related to the severity of LA, cerebral venous hypertension caused by downstream venous outflow impairment might play a major role in the pathogenesis of LA.Internal jugular vein is the main venous outflow pathway for cerebral venous drainage. The frequency of jugular venous reflux (JVR) is increased with aging. Hypertension, which has a decreased venous distensibility, might further exacerbate the sustained or long-term repetitive retrograde-transmitted cerebral venous pressure and venous outflow insufficiency caused by JVR. Clinically, JVR caused by a dural AV fistula does lead to cerebral hypoperfusion, white matter abnormalities, vasogenic edema and cognitive impairment in several published reports.JVR is suggested to play a key role in the pathogenesis of LA through a sustained or long-term repetitive retrograde-transmitted cerebral venous pressure and venous outflow insufficiency, which might lead to chronic cerebral venous hypertensions, abnormal cerebral venules structural changes, decreased cerebral blood flow, endothelial dysfunction, and vasogenic edema in cerebral white matters. © 2010 Elsevier Ltd.",age;aorta aneurysm;article;blood brain barrier;blood vessel compliance;brain blood flow;brain cortex;brain vein;cognitive defect;disease severity;human;hypertension;hypothalamus periventricular nucleus;internal jugular vein;intracranial pressure;leukoaraiosis;nuclear magnetic resonance imaging;pathogenesis;perfusion;pressure gradient;risk factor;sigmoid sinus;thorax pressure;vein blood flow;vein compliance;vein thrombosis;venous reflux;white matter,"Chung, C. P.;Hu, H. H.",2010,,,0,
4901,Jugular venous reflux and white matter abnormalities in alzheimer's disease: A pilot study,"To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age-and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings. Supplementary Material. © 2014-IOS Press and the authors. All rights reserved.",adult;aged;Alzheimer disease;article;brain blood flow;case control study;Clinical Dementia Rating;controlled study;disease association;disease severity;Doppler echography;female;geriatric patient;human;jugular vein;major clinical study;male;middle aged;mild cognitive impairment;Mini Mental State Examination;multiple regression;neurologic disease;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;pilot study;priority journal;risk factor;sample size;venous reflux;very elderly;white matter;white matter lesion;Excite II,"Chung, C. P.;Beggs, C.;Wang, P. N.;Bergsland, N.;Shepherd, S.;Cheng, C. Y.;Ramasamy, D. P.;Dwyer, M. G.;Hu, H. H.;Wang, P. N.",2014,,,0,
4902,Extensive metabolic and neuropsychological abnormalities associated with discrete infarction of the genu of the internal capsule,"Objective - The clinical presentation of capsular genu infarct varies. Prominent faciolingual weakness and subcortical dementia are the rule, but symptoms depend on the precise location and extension of the lesion beyond the genu. The aim was to characterise the radiographic, electroencephalographic, and neuropsychometric abnormalities in a woman who had a history of recurrent transient memory loss. Method - Case report. Results - Magnetic resonance imaging showed an infarct in the genu of the left internal capsule. Positron emission tomography scan demonstrated decreased metabolic activity in the ipsilateral temporal, occipitotemporal, and contralateral cerebellar hemispheres. Electroencephalography showed intermittent rhythmic delta activity in the left frontotemporal region, and findings on neuropsychometric evaluation were consistent with cognitive impairment. Follow up evaluation 7 months after the stroke showed improvement in some areas of the cognitive domain, but residual neuropsychometric and neurophysiological abnormalities persisted. Conclusion - This case illustrates that cerebral and cerebellar diaschisis may contribute to the symptomatic presentation and recovery from capsular genu infarct, although its precise role remains elusive.",,"Chukwudelunzu, F. E.;Meschia, J. F.;Graff-Radford, N. R.;Lucas, J. A.",2001,November,,0,
4903,Clinical and imaging features of mixed Alzheimer and vascular pathologies,"The co-occurrence of both Alzheimer disease (AD) pathology and vascular brain injury (VBI) is very common, especially amongst the oldest of old. In neuropathologic studies, the prevalence of AD, VBI, and mixed AD/VBI lesions ranks ahead of Lewy bodies and hippocampal sclerosis. In the modern era of structural magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) imaging, this review examines 1) the prevalence of mixed AD and VBI pathology, 2) the significance of these pathologies for cognitive impairment (AD and vascular cognitive impairment (VCI)), and 3) the diagnosis and treatment of mixed AD/VCI. Although epidemiologic studies report that vascular risk factors for arteriosclerosis increase the risk of incident AD, both autopsy and amyloid PET studies indicate that AD and VBI contribute additively, but independently, to the risk of dementia. The literature confirms the malignancy of AD and highlights the adverse effects of microinfarcts on cognitive function. For the clinical diagnosis of mixed AD/VCI, the presence of AD can be recognized by neuropsychological profile, structural imaging, cerebrospinal fluid biomarkers, and glucose PET and amyloid PET imaging. The diagnosis of VBI, however, still hinges predominantly on the structural MRI findings. Severe amnesia and atrophy of the hippocampus are characteristic of early AD, whereas the cognitive profile for VCI is highly variable and dependent on size and location of VBI. The cognitive profile of mixed AD/VBI is dominated by AD. With the notable exception of microinfarcts (which elude in vivo detection), infarcts, hemorrhages, and white matter hyperintensities on structural MRI currently represent the best markers for the presence VBI. Better markers that reflect the health and reactivity of intracerebral blood vessels are needed. For prevention and treatment, the type of underlying cerebrovascular disease (for example, arteriosclerosis or cerebral amyloid angiopathy) should be considered. It is likely that reduction of vascular risk factors for arteriosclerosis can significantly reduce vascular contributions to mixed dementia.",,"Chui, H. C.;Ramirez-Gomez, L.",2015,,10.1186/s13195-015-0104-7,0,
4904,Dementia due to subcortical ischemic vascular disease,"Ischemic vascular disease (IVD) is the second most common cause of dementia in the Western world. This article focuses on dementia resulting from subcortical ischemic vascular disease (SIVD), a subtype of IVD, which in many cases may be prevented. Hypertension and diabetes are the leading causes of small-artery disease, subcortical brain ischemia, and stepwise or slowing progressive decline in cognitive function. The pattern of cognitive impairment in SIVD, as compared with Alzheimer's disease, is characterized by greater impairment of executive function but better preservation of recognition memory. Structural neuroimaging studies, such as computed tomography and especially magnetic resonance imaging, are more sensitive than the clinical examination and can enable detection of subcortical lacunes and deep white matter changes that are clinically silent. Often the brain can be protected against SIVD by early diagnosis and management of risk factors. Once end-organ damage has occurred, however, treatment outcome is less satisfactory. The most common risk factors for SIVD-hypertension and diabetes mellitus-are best detected and managed in primary care settings.",,"Chui, H.",2001,2001,,0,
4905,"Memory loss, behavioral changes, and slurred speech in a 49-year-old man","A 49-year-old man presented with slurred speech, memory loss, and behavioral changes. His clinical course was marked by decline in functional status and cognition. He had poorly controlled hypertension and hyperlipidemia. Neuroimaging was remarkable for multiple subcortical white matter lesions. We discuss the diagnostic and therapeutic approach of rapidly progressing cognitive decline in the given clinical setting.",,"Chugh, C.;Lee, J. M.;Biller, J.",2011,,10.3389/fneur.2011.00027,0,
4906,CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy): an Australian perspective,"Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients.","Aged;Australia;Dementia, Multi-Infarct/*genetics/radiography;Exons;Genotype;Humans;Magnetic Resonance Imaging;Middle Aged;Point Mutation;Proto-Oncogene Proteins/*genetics;*Receptors, Cell Surface;Receptors, Notch","Chuah, T. L.;Tan, K. M.;Flanagan, S.;Hyland, V.;Sullivan, A. A.;Henderson, R.;MacMillan, J.;Lander, C.",2001,Sep,10.1054/jocn.2000.0848,0,
4907,Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: A review,"PURPOSE OF REVIEW: To provide a comprehensive review of diffusion tensor imaging in evaluating microstructural changes in the spectrum of cognitive decline from ageing to Alzheimer's disease, in particular focusing on mild cognitive impairment. RECENT FINDINGS: Mild cognitive impairment represents a transition phase between normal ageing and early Alzheimer's disease. Diffusion tensor imaging has emerged as a useful imaging modality that provides information about the structural integrity of tissue. In healthy ageing, diffusion tensor imaging abnormalities occur in the frontal regions, specifically the frontal white matter, anterior cingulum and the genu of the corpus callosum. Some studies report an anterior-posterior gradient change with greater abnormalities in the genu than the splenium of the corpus callosum and in the frontal than parietal white matter. In Alzheimer's disease, diffusion tensor imaging abnormalities are concentrated in the posterior regions: the parahippocampal gyrus, temporal white matter, splenium of corpus callosum and posterior cingulum. In mild cognitive impairment, changes seem to parallel those in Alzheimer's disease, with similar posterior regions showing abnormalities. SUMMARY: Due to the similarities in diffusion tensor imaging findings in both mild cognitive impairment and Alzheimer's disease, it is likely that diffusion tensor imaging has the potential to emerge as a useful clinical tool for early detection and monitoring of disease progression and treatment response in mild cognitive impairment/Alzheimer's disease patients. © 2008 Lippincott Williams & Wilkins, Inc.",,"Chua, T. C.;Wen, W.;Slavin, M. J.;Sachdev, P. S.",2008,February,,0,
4908,Diffusion tensor imaging of the posterior cingulate is a useful biomarker of mild cognitive impairment,"OBJECTIVES: Mild cognitive impairment (MCI) is recognized as a predementia state, but its definition is inconsistent and only 20%-30% develop dementia after 2 years. Biomarkers may help identify individuals at greatest risk of progressive decline. The authors examine a novel neuroimaging technique, diffusion tensor imaging (DTI) as a potential biomarker of MCI. DESIGN: Cross-sectional prospective study. SETTING: Subjects were recruited randomly using the electoral roll from two electorates in East Sydney, Australia. PARTICIPANTS: A community-dwelling sample (N = 249) and age 70-90 years. MEASUREMENTS: Screening to exclude dementia, comprehensive neuropsychiatric assessment, cognitive test battery, structural magnetic resonance imaging and DTI to obtain measures of fractional anisotropy (FA) and mean diffusivity (MD). MCI was diagnosed by standard criteria. RESULTS: After controlling for age, sex, and years of education, the amnestic MCI (aMCI) group demonstrated microstructural pathology in the parahippocampal white matter, frontal white matter, splenium of corpus callosum, and posterior cingulate region. The nonamnestic MCI (naMCI) group demonstrated microstructural pathology in the frontal white matter, internal capsule, occipital white matter, and the posterior cingulate region. A binary logistic regression model showed that DTI of the left posterior cingulate was significant in identifying persons with aMCI to an accuracy of 85.1%. Receiver operating characteristics curve analysis yielded a sensitivity of 80% and specificity of 60.3% in distinguishing aMCI from naMCI and the normal comparison group. CONCLUSION: DTI of the posterior cingulate region discriminates MCI from cognitively normal individuals with accuracy and has the potential to be used as a biomarker of MCI, in particular aMCI.","Aged;Aged, 80 and over;Amnesia/diagnosis/physiopathology;Biomarkers;Cognition Disorders/ diagnosis/physiopathology;Corpus Callosum/pathology/physiopathology;Diffusion Magnetic Resonance Imaging;Dominance, Cerebral/physiology;Extracellular Fluid/metabolism;Female;Frontal Lobe/pathology/physiopathology;Gyrus Cinguli/ pathology/physiopathology;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Nerve Fibers, Myelinated/pathology/physiology;Neural Pathways/pathology/physiopathology;Neuropsychological Tests;Occipital Lobe/pathology/physiopathology;Parahippocampal Gyrus/pathology/physiopathology;Risk Assessment","Chua, T. C.;Wen, W.;Chen, X.;Kochan, N.;Slavin, M. J.;Trollor, J. N.;Brodaty, H.;Sachdev, P. S.",2009,Jul,10.1097/JGP.0b013e3181a76e0b,0,
4909,Eight novel mutations in the ABCD1 gene and clinical characteristics of 25 Chinese patients with X-linked adrenoleukodystrophy,"Background: X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disease caused by mutations in the adenosine triphosphate-binding cassette D1 (ABCD1) gene. This study aimed to retrospectively investigate the clinical characteristics of 25 patients with X-ALD including members of large pedigrees, to analyze ABCD1 gene mutations, the effect of gene novel variants on ALD protein (ALDP) structure and function, and to expand gene mutation spectrum of Chinese patients. Methods: Twenty-five male patients diagnosed with X-ALD were enrolled in this study. The clinical characteristics of the patients were retrospectively summarized by reviewing medical records or telephone consultation. ABCD1 gene mutations were analyzed. The pathogenicity of novel missense variants was analyzed using cobalt constraint-based multiple protein alignment tool, polymorphism phenotyping, sorting intolerant from tolerant, Align-Grantham variation and Grantham deviation, and Swiss-Program Database Viewer 4.04 software, respectively. Results: Childhood cerebral form ALD (CCALD) is the most common phenotype (64%) in the 25 patients with X-ALD. The progressive deterioration of neurological and cognitive functions is the main clinical feature. The demyelination of the brain white matter and elevated plasma very long chain fatty acids (VLCFAs) were found in all patients. Different phenotypes were also presented within family members of the patients. Twenty-two different mutations including 8 novel mutations in the ABCD1 gene were identified in the 25 patients. Of the mutations, 63.6% were missense mutations and 34.8% located in exon 1. The amino acid residues of three novel missense mutations in eight species were highly conserved, and were predicted to be ""probably"" damaging to ALDP function. The other five novel mutations were splice, nonsense, deletion or duplication mutations. Conclusions: CCALD is the most common phenotype (64%) in our patients with X-ALD. Eight novel mutations in the ABCD1 gene identified are disease-causing mutations. Brain magnetic resonance imaging and plasma VLCFA determination should be performed for the patients who present with progressive deterioration of neurological development. World J Pediatr 2015;11(4):366-373",,"Chu, S. S.;Ye, J.;Zhang, H. W.;Han, L. S.;Qiu, W. J.;Gao, X. L.;Gu, X. F.",2015,1,,0,
4910,Diagnosis of intracranial vasculitis: a multi-disciplinary approach,"Intracranial vasculitis, or primary angiitis of the central nervous system (PACNS), is an uncommon, often fatal disorder that frequently responds to aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral angiography, and brain biopsy are diagnostic modalities that vary in invasiveness and diagnostic accuracy. The purpose of this study was to determine whether certain clinical or radiologic features were predictive of a diagnostic biopsy. Thirty consecutive patients undergoing brain biopsy to ""rule out vasculitis"" were studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1 had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5 had thickened vessels consistent with hypertensive changes, 5 had amyloid angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm, acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and angiographic changes associated with PACNS were nonspecific, overlapping extensively with changes of chronic hypertension and amyloid deposition. The predictive values of brain biopsy (90-100%) were significantly higher than those of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with aggressive immunosuppression was significantly greater than that associated with cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and leptomeningeal tissues is central to the multi-disciplinary approach to a patient with clinical suspicion of PACNS.",Adult;Aged;Biopsy;Brain/ pathology/radiography;Cerebral Angiography;Cerebrovascular Disorders/ diagnosis/pathology;Female;Granuloma/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies;Vasculitis/ diagnosis/pathology,"Chu, C. T.;Gray, L.;Goldstein, L. B.;Hulette, C. M.",1998,Jan,,0,
4911,Cerebral blood flow on xenon CT: correlation with the blood flow detected at the common carotid artery on ultrasonography,"To correlate cerebral blood flow (CBF) on xenon CT with the flow at common carotid artery (CCA) detected by color doppler ultrasonography, 82 patients (29 men, 53 women; 20-90 yrs) were examined. They included normal volunteers (n = 33), patients with cerebral infarction (n = 8), multiple lacunar infarcts (n = 12), dementia (n = 14), and parkinson disease (n = 15). Flow at the CCA was graded as extremely low (< 0.3 l/min), low (0.3-0.4), and normal (> 0.4). CBF was measured in the following distribution: anterior, middle, posterior cerebral arteries (ACA, MCA, PCA); white matter border zones (BZ); basal ganglia (BA), thalamus in two slices. CBF may be reduced in the BZ, cortical and deep gray matter with extremely low flow at CCA. We suggest that color doppler ultrasonography may aid in triage of patients for further CBF evaluation. As some overlap in CBF exists between normal and diseased groups with respect to low flow at CCA, color doppler ultrasonography must be evaluated in combination with xenon CT to reflect cerebral blood flow.","Adult;Aged;Aged, 80 and over;Brain Diseases/radiography/ultrasonography;Carotid Artery, Common/ultrasonography;Case-Control Studies;*Cerebrovascular Circulation;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed/*methods;Ultrasonography, Doppler, Color;*Xenon","Chu, B.;Warabi, T.;Aoki, K.;Narita, A.;Miyasaka, K.",2000,Feb,,0,
4912,"Magnetic resonance imaging in pre-senile dementia of the Alzheimer-type, multi-infarct dementia and Korsakoff's syndrome","Magnetic resonance imaging T1 values in Alzheimer's disease (ATD) were similar to age-matched controls although frontal T1 values tended to increase intraindividually with progression of the dementia. T1 values were raised, in both cortical grey and white matter, in Korsakoff's syndrome and multi-infarct dementia. T1 values appear of little value in studying the neuropathological changes in ATD in relationship to the neuropsychological deficits, but can assist in the differential diagnosis of pre-senile dementia.","Aged;Alcohol Amnestic Disorder/ pathology/psychology;Alzheimer Disease/ pathology/psychology;Atrophy;Brain/pathology;Dementia/ pathology/psychology;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Christie, J. E.;Kean, D. M.;Douglas, R. H.;Engleman, H. M.;St Clair, D.;Blackburn, I. M.",1988,May,,0,
4913,Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis,"The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor).",Amyotrophic lateral sclerosis;Cognition;Multimodal neuroimaging;Tract-based spatial statistics;Voxel-based morphometry,"Christidi, F.;Karavasilis, E.;Riederer, F.;Zalonis, I.;Ferentinos, P.;Velonakis, G.;Xirou, S.;Rentzos, M.;Argiropoulos, G.;Zouvelou, V.;Zambelis, T.;Athanasakos, A.;Toulas, P.;Vadikolias, K.;Efstathopoulos, E.;Kollias, S.;Karandreas, N.;Kelekis, N.;Evdokimidis, I.",2017,Apr 19,,0,
4914,Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques,"OBJECTIVE: Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). METHODS: We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. RESULTS: In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). CONCLUSIONS: PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.",Pathological laughing and crying;gray matter;neuroimaging;white matter,"Christidi, F.;Karavasilis, E.;Ferentinos, P.;Xirou, S.;Velonakis, G.;Rentzos, M.;Zouvelou, V.;Zalonis, I.;Efstathopoulos, E.;Kelekis, N.;Evdokimidis, I.",2017,Oct 15,,0,
4915,"Education, atrophy, and cognitive change in an epidemiological sample in early old age","OBJECTIVES:: To examine one version of the brain reserve hypothesis in a community sample of young-old participants. The authors investigated whether atrophy and white matter hyperintensities (WMH) were associated with cognitive decline, and whether this relationship was modified by the endowment of greater reserve as measured by years of education and brain size (intracranial volume ICV). DESIGN:: Longitudinal cohort study with 4-year follow-up. PARTICIPANTS:: A community sample of 416 adults aged 60-64 years at baseline. MEASUREMENTS:: Years of education and brain size were examined as measures of brain reserve. The association between these measures and brain atrophy and white matter hyperintensities (WMH) on magnetic resonance imaging and change in cognitive function over 4 years was determined. RESULTS:: Changes in cognitive test scores over 4 years had no correlation with years of education, atrophy, WMH, or ICV. There was no interaction of atrophy or level of WMH with education or brain size on cognitive change. CONCLUSION:: In a young-old sample, there is no direct evidence to support the brain reserve hypothesis as operationalized in this study. WMH and atrophy were not associated with cognitive change. © 2009 American Association for Geriatric Psychiatry.",,"Christensen, H.;Batterham, P. J.;MacKinnon, A. J.;Anstey, K. J.;Wen, W.;Sachdev, P. S.",2009,March,,0,
4916,[Familial orthochromatic leukodystrophy: clinicopathological study of two cases] Leucodystrophies orthochromatiques familiales,"This paper reports the clinico-pathological data in a French family with orthochromatic leukodystrophy. The parents were first cousins and had seven children. Among those, two sisters and one brother presented with neurological signs, with onset around the 5(th) decade, including a dementing syndrome of frontal type, a tetrapyramidal syndrome, seizures, and, in one sibling, a cerebellar syndrome. CT scan or MRI showed diffuse involvement of the white matter. The neurological signs worsened progressively leading to death within 11 and 22 months. Neuropathological examination was performed in two cases. It revealed characteristic orthochromatic leukodystrophy. In one case, the presence of pigmented macrophages and astrocytes was suggestive of Van Bogaert and Nyssen disease. However there were some atypical features including the absence of pigmented cells in the second case whose clinical course was shorter, and the cavitary appearance of the white matter changes with a relative increase in the number of oligodendrocytes raising the issue of a possible link between this condition and cavitary orthochromatic leukodystrophies.","Aged;Astrocytes/pathology;Brain/ pathology;Family;Female;France;Humans;Leukodystrophy, Globoid Cell/genetics/ pathology/ physiopathology;Macrophages/pathology;Male;Middle Aged;Pedigree","Chretien, F.;Servan, J.;Elghozi, D.;Fontaine, B.;Brion, F.;Ereau, T.;Chesneau, A. M.;Henin, D.;Gray, F.;Duclos, H.",2001,Feb,,0,
4917,[Familial orthochromatic leukodystrophy: clinicopathological study of two cases],"This paper reports the clinico-pathological data in a French family with orthochromatic leukodystrophy. The parents were first cousins and had seven children. Among those, two sisters and one brother presented with neurological signs, with onset around the 5(th) decade, including a dementing syndrome of frontal type, a tetrapyramidal syndrome, seizures, and, in one sibling, a cerebellar syndrome. CT scan or MRI showed diffuse involvement of the white matter. The neurological signs worsened progressively leading to death within 11 and 22 months. Neuropathological examination was performed in two cases. It revealed characteristic orthochromatic leukodystrophy. In one case, the presence of pigmented macrophages and astrocytes was suggestive of Van Bogaert and Nyssen disease. However there were some atypical features including the absence of pigmented cells in the second case whose clinical course was shorter, and the cavitary appearance of the white matter changes with a relative increase in the number of oligodendrocytes raising the issue of a possible link between this condition and cavitary orthochromatic leukodystrophies.","Aged;Astrocytes/pathology;Brain/*pathology;Family;Female;France;Humans;Leukodystrophy, Globoid Cell/genetics/*pathology/*physiopathology;Macrophages/pathology;Male;Middle Aged;Pedigree","Chretien, F.;Servan, J.;Elghozi, D.;Fontaine, B.;Brion, F.;Ereau, T.;Chesneau, A. M.;Henin, D.;Gray, F.;Duclos, H.",2001,Feb,,0,
4918,Cerebral amyloid angiopathy revealed by leptomeningitis: A significant MRI aspect,"Cerebral amyloid angiopathy (CAA) is a frequent pathology of the demented and non-demented elderly. Its expression is mainly hemorrhagic - lobar intracerebral hemorrhage, brain microbleeds, superficial hemosiderosis - but also ischemic - white matter changes, small cortical infarcts. It can also be revealed by transient focal neurological symptoms and/or cognitive impairment. We report the case of a 64-year-old woman who presented brief stereotypic episodes of left brachio-facial numbness. The cerebral MRI showed focal pial FLAIR hyperintensities enhanced by gadolinium and a superficial hemosiderosis of the right central sulcus. The etiological investigation of leptomeningitis found no evidence for a neoplastic, infectious or inflammatory cause. Because of the clinical worsening and the MRI progression of the pial lesions, a cortico-meningeal biopsy was obtained and revealed CAA associated with intense microglial activation, which did not match the usual aspect of the inflammatory forms of CAA. This is an atypical presentation of CAA characterized by isolated and rapidly progressive leptomeningeal abnormalities. This case report highlights the heterogeneous spectrum of the clinical and neuroradiological CAA presentations and highlights the need to update current diagnostic criteria. © 2012 Elsevier Masson SAS.",gadolinium;adult;article;case report;cell activation;contrast enhancement;disease course;female;general condition deterioration;hemosiderosis;human;leptomeningitis;meningeal biopsy;meningitis;microglia;nuclear magnetic resonance imaging;paresthesia;vascular amyloidosis,"Chouraki, A.;Rollin-Sillaire, A.;Cordonnier, C.;Deramecourt, V.;Pasquier, F.",2012,,,0,
4919,Persistent Klüver-Bucy syndrome after bilateral temporal lobe infarction,"Klüver-Bucy (KBS) syndrome is a rare and complicated neurobehavioral syndrome in humans resulting from damage of bilateral anterior temporal portion, especially the amygdala. It can be seen in association with a variety of etiologies. Stroke is a rarely reported. Here we present a 50-year-old right handed man who developed persistent KBS after cardioembolic stroke involving bilateral lateral temporal lobes. He exhibited all clinical features of KBS including visual agnosia, hypersexuality, placidity, hyperorality and hypermetamorphosis. The anatomical basis of pathophysiolgy, clinical course and possible treatment are discussed.",anticoagulant agent;carbamazepine;haloperidol;methylphenidate;quetiapine;adult;aggression;agnosia;aphasia;article;behavior disorder;brain infarction;case report;cerebrovascular accident;computer assisted tomography;confusion;electroencephalography;heart atrium thrombosis;human;hypersexuality;Kluver Bucy syndrome;male;neurologic examination;nuclear magnetic resonance imaging;somnolence;speech disorder;temporal lobe,"Chou, C. L.;Lin, Y. J.;Sheu, Y. L.;Lin, C. J.;Hseuh, I. H.",2008,,,0,
4920,Localized cerebral proton MR spectroscopy in HIV infection and AIDS,"PURPOSE: To document differences in the cerebral proton MR spectra of patients with early and late stages of human immunodeficiency virus (HIV) infection. METHOD: We studied the relative N-acetyl-aspartate (NAA) levels by localized proton spectroscopy of the parietooccipital region of the brain in 43 HIV-seropositive patients, including 26 with an acquired immunodeficiency syndrome (AIDS)-defining diagnosis, and in eight control subjects. RESULTS: Reduced relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1-associated cognitive/motor complex against neurologically healthy patients (P < .007); 3) with encephalopathic changes on MR against those with normal imaging (P < .001); and 4) on follow-up against their results on initial study (P < .03). CONCLUSIONS: By clinical (Centers for Disease Control classification) and radiologic (MR evidence of white-matter disease) criteria indicating late-stage HIV infection, reduced relative levels of NAA have been demonstrated. Spectroscopic abnormalities can be quantitatively tracked with time. This paper demonstrates the clinical use of detecting NAA as a putative in vivo measure of the neuronal loss that has been demonstrated in postmortem studies of patients with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated cognitive/motor complex, is thought to be attributable directly or indirectly to the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative noninvasive indicator of this aspect of cerebral involvement in HIV disease.","AIDS Dementia Complex/metabolism;AIDS-Related Complex/metabolism;Acquired Immunodeficiency Syndrome/ metabolism;Adult;Aspartic Acid/analogs & derivatives/analysis;Brain Chemistry;Choline/analysis;Creatine/analysis;Diagnosis, Differential;HIV Seropositivity/ metabolism;Humans;Magnetic Resonance Spectroscopy;Middle Aged","Chong, W. K.;Paley, M.;Wilkinson, I. D.;Hall-Craggs, M. A.;Sweeney, B.;Harrison, M. J.;Miller, R. F.;Kendall, B. E.",1994,Jan,,0,
4921,"Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7  μm optical coherence tomography","A spectral/Fourier domain optical coherence tomography (OCT) intravital microscope using a supercontinuum light source at 1.7 μm was developed to study subcortical structures noninvasively in the living mouse brain. The benefits of 1.7 μm for deep tissue brain imaging are demonstrated by quantitatively comparing OCT signal attenuation characteristics of cortical tissue across visible and near-infrared wavelengths. Imaging of hippocampal tissue architecture and white matter microvasculature are demonstrated in vivo through thinned-skull, glass coverslip-reinforced cranial windows in mice. Applications of this novel platform include monitoring disease progression and pathophysiology in rodent models of Alzheimer's disease and subcortical dementias, including vascular dementia.",animal;C57BL mouse;cytology;device failure analysis;devices;equipment design;hippocampus;illumination;image enhancement;intravital microscopy;male;microvasculature;mouse;optical coherence tomography;procedures;reproducibility;sensitivity and specificity;vascularization;white matter,"Chong, S. P.;Merkle, C. W.;Cooke, D. F.;Zhang, T.;Radhakrishnan, H.;Krubitzer, L.;Srinivasan, V. J.",2015,,10.1364/ol.40.004911,0,
4922,"Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7 mum optical coherence tomography","A spectral/Fourier domain optical coherence tomography (OCT) intravital microscope using a supercontinuum light source at 1.7 mum was developed to study subcortical structures noninvasively in the living mouse brain. The benefits of 1.7 mum for deep tissue brain imaging are demonstrated by quantitatively comparing OCT signal attenuation characteristics of cortical tissue across visible and near-infrared wavelengths. Imaging of hippocampal tissue architecture and white matter microvasculature are demonstrated in vivo through thinned-skull, glass coverslip-reinforced cranial windows in mice. Applications of this novel platform include monitoring disease progression and pathophysiology in rodent models of Alzheimer's disease and subcortical dementias, including vascular dementia.",,"Chong, S. P.;Merkle, C. W.;Cooke, D. F.;Zhang, T.;Radhakrishnan, H.;Krubitzer, L.;Srinivasan, V. J.",2015,Nov 1,,0,
4923,Influence of cerebrovascular disease on brain networks in prodromal and clinical Alzheimer's disease,"Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnostic imaging/physiopathology;Brain/ diagnostic imaging/physiopathology;Case-Control Studies;Cerebrovascular Disorders/ diagnostic imaging/physiopathology;Cognitive Dysfunction/ diagnostic imaging/physiopathology;Executive Function;Female;Functional Neuroimaging;Hippocampus/diagnostic imaging/pathology;Humans;Magnetic Resonance Imaging;Male;Neural Pathways/diagnostic imaging/physiopathology;Organ Size;Alzheimer's disease;cerebrovascular disease;intrinsic functional connectivity;prodromal stage;structural covariance","Chong, J. S. X.;Liu, S.;Loke, Y. M.;Hilal, S.;Ikram, M. K.;Xu, X.;Tan, B. Y.;Venketasubramanian, N.;Chen, C. L.;Zhou, J.",2017,Nov 1,,0,
4924,Multimodal imaging evaluation of excessive daytime sleepiness in Parkinson's disease,"PURPOSE OF THE STUDY: The multimodal imaging investigation of excessive daytime sleepiness (EDS) in Parkinson's disease (PD). The role of dopaminergic treatment and other clinical parameters was also evaluated. MATERIALS AND METHODS: Seventeen non-demented PD patients with EDS (PD-EDS) and 17 PD patients without EDS were enrolled. Clinical, treatment and MRI data were acquired. Gray matter (GM) volume was examined with voxel-based morphometry, while white matter (WM) integrity was assessed with diffusion tensor imaging by means of fractional anisotropy, mean diffusivity, axial diffusivity (AD) and radial diffusivity measures. RESULTS: Increased regional GM volume was found in the PD-EDS group bilaterally in the hippocampus and parahippocampal gyri. Increased AD values were also shown in the PD-EDS group, in the left anterior thalamic radiation and the corticospinal tract and bilaterally in the superior corona radiata and the superior longitudinal fasciculus. Levodopa equivalent dose differed significantly between the groups and was the only predictor of EDS, while the only predictor of the Epworth sleepiness scale score in the PD-EDS group was the dopamine-agonist dose. Increased frequency of gamblers was also observed in the PD-EDS group. CONCLUSIONS: Regional GM increases and increased AD values in certain WM tracts were found in the PD-EDS group. The changes could result from disinhibited signaling pathways or represent compensatory changes in response to anatomical or functional deficits elsewhere. The study findings support also the contribution of the total dopaminergic load in the development of EDS, while the dose of dopamine agonists was found to predict the severity of the disorder.",,"Chondrogiorgi, M.;Tzarouchi, L. C.;Zikou, A. K.;Astrakas, L. G.;Kosta, P.;Argyropoulou, M. I.;Konitsiotis, S.",2016,May,10.3109/00207454.2015.1023437,0,
4925,Diffusion tensor imaging of frontal white matter microstructure in early Alzheimer's disease: a preliminary study,"Several investigators have suggested that the pathological progression of Alzheimer's disease appears to recapitulate the developmental maturation pattern, a process termed retrogenesis. Diffusion tensor imaging was used to test the hypothesis that the microstructural integrity of superior frontal and temporal white matter, one of the last regions to mature, would be reduced in vivo in early Alzheimer's disease. Five consecutive slices, from the orbitofrontal to periventricular frontal regions, as well as temporal and corpus callosal white matter regions, were sampled. Fractional anisotropy, mean diffusivity, axial diffusion, and radial diffusion of 10 patients with early Alzheimer's disease and 10 age-similar healthy control subjects were compared. Patients with Alzheimer's disease were found to have significantly reduced fractional anisotropy, increased mean diffusivity, and increased radial diffusion in superior frontal white matter. These data suggest that the integrity of periventricular frontal white matter rather than orbitofrontal white matter appears to be altered in early Alzheimer's disease and that the white matter abnormalities involve compromised myelin, consistent with the retrogenesis theory.",Aged;Alzheimer Disease/ diagnosis/ pathology;Anisotropy;Case-Control Studies;Diffusion Magnetic Resonance Imaging;Disease Progression;Female;Frontal Lobe/ pathology;Humans;Male;Temporal Lobe/ pathology,"Choi, S. J.;Lim, K. O.;Monteiro, I.;Reisberg, B.",2005,Mar,10.1177/0891988704271763,0,
4926,Diffusion-weighted MRI in vascular dementia,"OBJECTIVE: To examine the ability of diffusion-weighted MRI (DWI) to detect ongoing cerebral ischemia in patients with vascular dementia (VaD). BACKGROUND: VaD due to small-vessel disease results from the cumulative impact of recurrent cerebral ischemia. Cerebral ischemia may produce clinical manifestations, producing the ""stepwise"" decline characteristic of VaD. Conventional MRI can detect small regions of ischemic damage but cannot determine when injury developed. In contrast, DWI shows sensitivity in detecting ischemia of recent onset. DESIGN/METHODS: Patients with VaD (n = 30) underwent DWI in addition to standard MRI sequences. Patients were divided into two groups according to the presence of new focal deficits or mental change within 10 days before MRI. In 10 patients of positive group, symptomatic neurologic decline occurred an average of 4.2 days before the imaging procedure. RESULTS: Seven (70%) of 10 patients with a recent neurologic event showed 15 new regions of signal abnormality on DWI. The anatomic distribution of signal change could account for the patients' new symptoms or signs in all but one patient. Similar signal abnormality was detected in 4 (20%) of 20 patients without a recent neurologic event. New foci of altered signal intensity were distinguishable from prior injuries only with DWI. No significant difference was found between patients with and without DWI abnormalities in gender, age, Mini-Mental State Examination score, Hachinski Ischemic Score, vascular risk factors, or severity of increased signal on T2-weighted MRI scans. CONCLUSION: Small foci of abnormal signal on diffusion-weighted MRI (DWI), presumably representing recent small infarcts, occur often in vascular dementia (VaD) from small-vessel disease, even in patients without a recent ""stepwise decline."" The results suggest that DWI might be used to monitor VaD progression in future observational and interventional studies of this disorder.","Aged;Aged, 80 and over;Cognition Disorders/etiology;Dementia, Vascular/ diagnosis/psychology;Disease Progression;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Memory Disorders/etiology;Middle Aged;Nervous System Diseases/etiology/physiopathology","Choi, S. H.;Na, D. L.;Chung, C. S.;Lee, K. H.;Na, D. G.;Adair, J. C.",2000,Jan 11,,0,
4927,"Headache among CADASIL patients with R544C mutation: Prevalence, characteristics, and associations","Background and aim: There are variations of migraine prevalence in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) among different regions of the world. Previous studies on Asian CADASIL patients have not provided detailed descriptions of the characteristics of their headaches. The aims of this study were to determine prevalence and characteristics of headaches and to investigate associations between headache and other clinical symptoms or brain magnetic resonance imaging (MRI) findings among homogenous group of patients having the same R544C mutation. Methods: In this cross-sectional study, we enrolled 53 CADASIL patients with the R544C mutation between May 2010 and April 2011. We obtained the history of headache using a structured questionnaire and detailed interview. Other clinical features and brain MRI findings were also assessed for potential associations. Results: Overall headache prevalence was 45.3% (24 patients). Among them, 21 patients (87.5%) were classified as having tension-type headache, followed by migraine (two patients) and unclassifiable headaches (one patient). Except for alcohol consumption, no significant associations were observed between the headaches and other clinical features or brain MRI findings. Conclusion: Migraine was found in only 3.8% of CADASIL patients with the R544C mutation. Such a low prevalence of migraine may hinder clinical detection of CADASIL among ethnically Asian patients. © International Headache Society 2013.",,"Choi, J. C.;Song, S. K.;Lee, J. S.;Kang, S. Y.;Kang, J. H.",2014,January,,0,
4928,Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small blood vessels caused by mutations in the NOTCH3 gene. Several characteristic population-specific clinical phenotypes and neuroimaging features have been reported in CADASIL. This study investigated the clinical stroke presentation and cranial magnetic resonance imaging (MRI) findings in a group of patients with CADASIL. We reviewed the clinical stroke presentation and brain MRI findings in 73 consecutive Korean patients aged >18 years diagnosed with CADASIL between May 2004 and April 2009. Brain MRI images were also scored for lacunar infarction and cerebral microbleeds. Intracranial atherosclerosis (ICAS) was assessed by magnetic resonance angiography. Disability was measured with the modified Rankin scale (mRS) and classified as good (mRS score 0-2) or poor (mRS score 3-5). In this study, 65 of the 73 patients (90.3%) had the same R544C genotype. A total of 40 episodes of cerebral infarction were confirmed in 31 patients, with a mean age at onset of 58.8 +/- 11.4 years (range, 38-76 years). Twelve patients (16.9%) had ICAS, and 5 of these patients had symptomatic stenoses. Intracerebral hemorrhage occurred in 9 patients (12.3%). Both intracerebral hemorrhage and ICAS were associated with poor clinical outcome. Our data demonstrate the diversity of clinical stroke presentation according to ethnicity and vascular risk factors.","Adult;Aged;Asian Continental Ancestry Group/ genetics/statistics & numerical data;CADASIL/ ethnology/ genetics;Female;Genetic Predisposition to Disease/ethnology/genetics;Humans;Islands/epidemiology;Male;Middle Aged;Phenotype;Point Mutation;Receptors, Notch/ genetics;Republic of Korea/epidemiology;Risk Factors;Stroke/diagnosis/ethnology/genetics","Choi, J. C.;Song, S. K.;Lee, J. S.;Kang, S. Y.;Kang, J. H.",2013,Feb,10.1016/j.jstrokecerebrovasdis.2011.07.002,0,
4929,Screening for NOTCH3 gene mutations among 151 consecutive Korean patients with acute ischemic stroke,"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of cerebral small blood vessels caused by mutations in the NOTCH3 gene. The initial detection of CADASIL may be more difficult among Asian populations because common clinical phenotypes and neuroimaging findings are not frequently found in these populations. The purpose of this study was to screen the NOTCH3 gene for mutations among consecutive patients with acute ischemic stroke from our region in Korea. METHODS: Between April 2008 and March 2009, 151 consecutive patients with acute ischemic stroke were screened for NOTCH3 mutations. All patients underwent a detailed clinical examination and structured interview for clinical symptoms and family history. We reviewed brain magnetic resonance imaging data from stroke patients to assess the severity of white-matter hyperintensity lesions, the number of cerebral microbleeds, and the number of lacunar infarctions. Polymerase chain reaction was used to screen exons 3, 4, 6, 11, and 18 of the NOTCH3 gene. RESULTS: Among 151 consecutive patients with acute ischemic stroke, 6 patients (4.0%; 95% confidence interval [CI] 0.9-7.1) possessed a NOTCH3 gene mutation. All patients exhibited the same R544C mutation in exon 11. Four of these 6 patients presented with large artery atherosclerosis. The prevalence of CADASIL in patients with neuroimaging features consistent with advanced small-vessel disease was 36.0% (95% CI 8.0-64.8). CONCLUSIONS: In this region, NOTCH3 gene mutations are frequently found in acute stroke patients who present with neuroimaging features consistent with advanced small-vessel disease.","Aged;Aged, 80 and over;Asian Continental Ancestry Group/genetics;Brain Ischemia/diagnosis/ethnology/ genetics;CADASIL/diagnosis/ethnology/ genetics;DNA Mutational Analysis;Exons;Female;Genetic Predisposition to Disease;Genetic Testing/methods;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Phenotype;Polymerase Chain Reaction;Predictive Value of Tests;Receptors, Notch/ genetics;Republic of Korea/epidemiology;Stroke/diagnosis/ethnology/ genetics","Choi, J. C.;Lee, K. H.;Song, S. K.;Lee, J. S.;Kang, S. Y.;Kang, J. H.",2013,Jul,10.1016/j.jstrokecerebrovasdis.2011.10.013,0,
4930,Intracerebral hemorrhages in CADASIL,"Intracerebral hemorrhage (ICH) has been described only sporadically for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, cerebral microbleeds (CMBs) were found in 31% to 69% of the patients with CADASIL, and this predicted an increased risk of ICH. In this study, the authors found that 25% of the symptomatic patients with CADASIL had ICHs, and their development was closely related to the number of CMBs. ©2006AAN Enterprises, Inc.",adult;aged;article;brain hemorrhage;CADASIL;clinical article;clinical feature;diagnostic imaging;female;human;image analysis;male;nuclear magnetic resonance imaging;patient assessment;physical disability;priority journal;radiologist;Rankin scale;sample size;scoring system;white matter,"Choi, J. C.;Kang, S. Y.;Kang, J. H.;Park, J. K.",2006,,,0,
4931,Large cerebral artery involvement in CADASIL,"The authors evaluated the involvement of large cerebral artery in 13 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with angiography (12 MR and one conventional). Five patients (38%) showed stenosis: at the middle cerebral artery in three, vertebral artery in one, and the internal carotid artery in one. The stenosis persisted on follow-up angiogram in two patients. There were no differences in risk factors between patients with angiographic abnormality and those without, suggesting occasional involvement of large vessels in CADASIL.","Adult;Aged;Brain/blood supply/pathology/radiography;CADASIL/*diagnosis/physiopathology;Carotid Stenosis/diagnosis/physiopathology;Cerebral Angiography;Cerebral Arteries/*pathology/physiopathology/radiography;Disease Progression;Female;Humans;Infarction, Middle Cerebral Artery/diagnosis/physiopathology;Magnetic Resonance Angiography;Male;Middle Aged;Predictive Value of Tests;Prognosis;Risk Factors;Vertebrobasilar Insufficiency/diagnosis/physiopathology","Choi, E. J.;Choi, C. G.;Kim, J. S.",2005,Oct 25,10.1212/01.wnl.0000180965.79209.50,0,
4932,Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion,"BACKGROUND AND PURPOSE: Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. RESULTS: Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. CONCLUSIONS: White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.",,"Choi, B. R.;Kim, D. H.;Back, D. B.;Kang, C. H.;Moon, W. J.;Han, J. S.;Choi, D. H.;Kwon, K. J.;Shin, C. Y.;Kim, B. R.;Lee, J.;Han, S. H.;Kim, H. Y.",2016,Feb,10.1161/strokeaha.115.011679,0,
4933,Chronic cerebral hypoperfusion and plasticity of the posterior cerebral artery following permanent bilateral common carotid artery occlusion,"Vascular dementia (VaD) is a group of heterogeneous diseases with the common feature of cerebral hypoperfusion. To identify key factors contributing to VaD pathophysiology, we performed a detailed comparison of Wistar and Sprague-Dawley (SD) rats subjected to permanent bilateral common carotid artery occlusion (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a reference memory test using a five-radial arm maze with tactile cues. Continuous monitoring of cerebral blood flow (CBF) was performed with a laser Doppler perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for evaluation of the brain vasculature and white matter damage after BCCAo. We found reference memory impairment in Wistar rats, but not in SD rats. Moreover, our LDPI system revealed that Wistar rats had significant hypoperfusion in the brain region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats showed more profound CBF reduction in the forebrain region than did SD rats. Post-mortem analysis of brain vasculature demonstrated greater PCA plasticity at all time points after BCCAo in Wistar rats. Finally, we confirmed white matter rarefaction that was only observed in Wistar rats. Our studies show a comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to severe PCA dolichoectasia, which correlated well with white matter lesion and memory decline.",Bilateral common carotid artery occlusion;Chronic cerebral hypoperfusion;Dolichoectasia;Sprague-Dawley strain;Vascular dementia;Wistar strain,"Cho, K. O.;Kim, S. K.;Kim, S. Y.",2017,Nov,,0,
4934,Social-emotional dysfunction after isolated right anterior insular infarction,,adult;anterior insular infaction;brain infarction;brain region;case report;cognitive defect;depression;dysarthria;electrocardiography;emotional disorder;female;frontotemporal dementia;functional magnetic resonance imaging;atrial fibrillation;human;letter;magnetic resonance angiography;mental disease;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;priority journal;single photon emission computer tomography;social behavior;speech disorder;tachycardia,"Cho, H. J.;Kim, S. J.;Hwang, S. J.;Jo, M. K.;Kim, H. J.;Seeley, W. W.;Kim, E. J.",2012,,,0,
4935,White matter changes in 80 mild cognitive impairment patients using magnetic resonance imaging,"BACKGROUND: Many studies have suggested that one possible etiology of mild cognitive impairment is small vessel cerebrovascular disease, which is associated with small subcortical infarcts and white matter abnormalities. These white matter changes have been detected as white matter hyperintensity (WMH) using magnetic resonance imaging. WMH may be associated with frontal lobe dysfunction. OBJECTIVE: To examine white matter changes in mild cognitive impairment patients of different subtypes, and to evaluate the correlation between white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes. DESIGN, TIME AND SETTING: The neurophysiological, comparison study was performed at the Department of Neurology Memory Clinic, Ulsan University Hospital, South Korea, between March 2007 and March 2008. PARTICIPANTS: Out of a total of 83 subjects with clinically diagnosed mild cognitive impairment at the out-patient clinic, 3 subjects with severe WMH were excluded. A total of 80 subjects were included in this study. No patients suffered from cognitive impairment induced by neurological diseases, mental disorders, or somatic diseases. In accordance with magnetic resonance imaging results, the patients were assigned to two subtypes: 56 subjects without WMH and 24 subjects with WMH. METHODS: All patients were subjected to a standard neuropsychological battery using the Korean version of the Mini-Mental State Examination, Clinical Dementia Rating, and comprehensive Seoul Neuropsychological Screening Battery. The Clinical Dementia Rating reflected general cognitive function of patients. Results from the Seoul Neuropsychological Screening Battery reflected attention, language function, visuospatial function, verbal memory, nonverbal memory, long-term memory, and frontal/executive function. Magnetic resonance imaging was used to map changes in the brain. MAIN OUTCOME MEASURES: The association between various white matter changes and neuropsychological characteristics, demographic information, vascular risk factors, and mild cognitive impairment subtypes was measured, based primarily on neuropsychological profiles using statistical methods. RESULTS: WMH was significantly associated with neuropsychological characteristics in MCI patients (P < 0.05 or P < 0.01), in particular with frontal/executive dysfunction. WMH was significantly correlated with age (P = 0.022) and vascular risk factors (P = 0.006), independent of gender and MCI subtypes. CONCLUSION: WMH was significantly associated with frontal/executive dysfunction in mild cognitive impairment.",,"Cho, H.;Kwon, J. H.;Kim, S. Y.",2009,September,,0,
4936,Impact of smoking on neurodegeneration and cerebrovascular disease markers in cognitively normal men,"BACKGROUND AND PURPOSE: Smoking is a major risk factor for cognitive decline and dementia. However, the exact pathobiology of smoking remains unknown. The effects of smoking on cortical thickness as a biomarker of neurodegeneration or white matter hyperintensities and lacunes as biomarkers of cerebrovascular burden were concurrently evaluated. METHODS: Our study included 977 cognitively normal men who visited a health promotion centre and underwent medical check-ups, including 3.0 T magnetic resonance imaging. Participants were categorized into never smoker, past smoker or current smoker groups and pack-years and the years of smoking cessation were used as continuous variables. RESULTS: The current smoker group exhibited cortical thinning in frontal and temporo-parietal regions compared with the never smoker group. These effects were particularly prominent in smokers with a high cumulative exposure to smoking in the current smoker group. However, there was no association between smoking and the severity of white matter hyperintensity or number of lacunes. CONCLUSION: Our findings indicate that smoking might impact on neurodegeneration rather than cerebrovascular burdens in cognitively normal men, suggesting that smoking might be an important modifiable risk factor for the development of Alzheimer's disease.",,"Cho, H.;Kim, C.;Kim, H. J.;Ye, B. S.;Kim, Y. J.;Jung, N. Y.;Son, T. O.;Cho, E. B.;Jang, H.;Lee, J.;Kang, M.;Shin, H. Y.;Jeon, S.;Lee, J. M.;Kim, S. T.;Choi, Y. C.;Na, D. L.;Seo, S. W.",2016,Jan,10.1111/ene.12816,0,
4937,Abnormal integrity of corticocortical tracts in mild cognitive impairment: A diffusion tensor imaging study,"Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders. Copyright © The Korean Academy of Medical Sciences.",,"Cho, H.;Dong, W. Y.;Young, M. S.;Beum, S. K.;Yeong, I. K.;Young, B. C.;Kwang, S. L.;Yong, S. S.;Yoon, B.;Kim, W.;Kook, J. A.",2008,June,,0,
4938,Effect of kidney dysfunction on cortical thinning in patients with probable Alzheimer's disease dementia,"There are some studies identifying the association between kidney dysfunction and cognitive impairment through various mechanisms including small vessel disease. However, results concerning the relationship between kidney dysfunction and cortical atrophy have been inconsistent. Thus, we aimed to evaluate the relationship among kidney dysfunction, small vessel disease, and cortical thinning in probable Alzheimer's disease (AD) dementia patients. Patients consisted of 162 subjects with probable AD dementia who underwent high-resolution T1-weighted volumetric magnetic resonance imaging (MRI) scans using the same scanner. The estimated glomerular filtration rate (GFR) was calculated and divided into the quartiles of patients for comparison. Volume of white matter hyperintensities (WMH) was automatically measured. Two neurologists counted the number of lacunes. Cortical thickness was measured using a surface-based method. GFR was not associated with WMH and the number of lacunes. However, the lowest quartile group of GFR (GFR 1) had cortical thinning in each lobe, compared to the highest quartile group of GFR (GFR 4). The topography of cortical thinning in the GFR 1 group was distributed predominantly in temporoparietal regions, compared to GFR 4. After further adjustment of small vessel disease MRI markers, the association between GFR and the cortical thinning remained. Our findings suggested that kidney dysfunction, represented by GFR, was related to temporoparietal thinning independent of small vessel disease in probable AD dementia patients.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ epidemiology/ physiopathology;Cerebral Cortex/ pathology/physiopathology;Cross-Sectional Studies;Female;Glomerular Filtration Rate/physiology;Humans;Kidney Diseases/ diagnosis/ epidemiology/physiopathology;Kidney Function Tests/methods;Male;Middle Aged;Organ Size","Cho, E. B.;Seo, S. W.;Kim, H.;Lee, J. M.;Yoon, U.;Im, K.;Kim, G. H.;Noh, Y.;Cho, H.;Yoon, C. W.;Kim, H. J.;Na, D. L.",2013,,10.3233/jad-2012-121180,0,
4939,Involvement of glial P2Y(1) receptors in cognitive deficit after focal cerebral stroke in a rodent model,"BACKGROUND: Neuroinflammation is associated with many conditions that lead to dementia, such as cerebrovascular disorders or Alzheimer's disease. However, the specific role of neuroinflammation in the progression of cognitive deficits remains unclear. To understand the molecular mechanisms underlying these events we used a rodent model of focal cerebral stroke, which causes deficits in hippocampus-dependent cognitive function. METHODS: Cerebral stroke was induced by middle cerebral artery occlusion (MCAO). Hippocampus-dependent cognitive function was evaluated by a contextual fear conditioning test. The glial neuroinflammatory responses were investigated by immunohistochemical evaluation and diffusion tensor MRI (DTI). We used knockout mice for P2Y(1) (P2Y(1)KO), a glial ADP/ATP receptor that induces the release of proinflammatory cytokines, to examine the links among P2Y(1)-mediated signaling, the neuroinflammatory response, and cognitive function. RESULTS: Declines in cognitive function and glial neuroinflammatory response were observed after MCAO in both rats and mice. Changes in the hippocampal tissue were detected by DTI as the mean diffusivity (MD) value, which corresponded with the cognitive decline at 4 days, 1 week, 3 weeks, and 2 months after MCAO. Interestingly, the P2Y(1)KO mice with MCAO showed a decline in sensory-motor function, but not in cognition. Furthermore, the P2Y(1)KO mice showed neither a hippocampal glial neuroinflammatory response (as assessed by immunohistochemistry) nor a change in hippocampal MD value after MCAO. In addition, wild-type mice treated with a P2Y(1)-specific antagonist immediately after reperfusion did not show cognitive decline. CONCLUSION: Our findings indicate that glial P2Y(1) receptors are involved in the hippocampal inflammatory response. The findings from this study may contribute to the development of a therapeutic strategy for brain infarction, targeting the P2Y(1) receptor.","Algorithms;Animals;Behavior, Animal/physiology;Cognition Disorders/etiology/*physiopathology/psychology;Diffusion Tensor Imaging;Hippocampus/pathology;Image Processing, Computer-Assisted;Immunohistochemistry;Infarction, Middle Cerebral Artery/genetics/pathology/psychology;Male;Mice;Mice, Inbred C57BL;Mice, Knockout;Rats;Rats, Sprague-Dawley;Receptors, Purinergic P2Y1/*genetics/*physiology;Stroke/*genetics","Chin, Y.;Kishi, M.;Sekino, M.;Nakajo, F.;Abe, Y.;Terazono, Y.;Hiroyuki, O.;Kato, F.;Koizumi, S.;Gachet, C.;Hisatsune, T.",2013,,10.1186/1742-2094-10-95,0,
4940,3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry,"35% of HIV-infected patients have cognitive impairment, but the profile of HIV-induced brain damage is still not well understood. Here we used tensor-based morphometry (TBM) to visualize brain deficits and clinical/anatomical correlations in HIV/AIDS. To perform TBM, we developed a new MRI-based analysis technique that uses fluid image warping, and a new alpha-entropy-based information-theoretic measure of image correspondence, called the Jensen-Renyi divergence (JRD). METHODS: 3D T1-weighted brain MRIs of 26 AIDS patients (CDC stage C and/or 3 without HIV-associated dementia; 47.2+/-9.8 years; 25M/1F; CD4+ T-cell count: 299.5+/-175.7/microl; log10 plasma viral load: 2.57+/- 1.28 RNA copies/ml) and 14 HIV-seronegative controls (37.6+/-12.2 years; 8M/6F) were fluidly registered by applying forces throughout each deforming image to maximize the JRD between it and a target image (from a control subject). The 3D fluid registration was regularized using the linearized Cauchy-Navier operator. Fine-scale volumetric differences between diagnostic groups were mapped. Regions were identified where brain atrophy correlated with clinical measures. RESULTS: Severe atrophy ( approximately 15-20% deficit) was detected bilaterally in the primary and association sensorimotor areas. Atrophy of these regions, particularly in the white matter, correlated with cognitive impairment (P = 0.033) and CD4+ T-lymphocyte depletion (P = 0.005). CONCLUSION: TBM facilitates 3D visualization of AIDS neuropathology in living patients scanned with MRI. Severe atrophy in frontoparietal and striatal areas may underlie early cognitive dysfunction in AIDS patients, and may signal the imminent onset of AIDS dementia complex.","Acquired Immunodeficiency Syndrome/complications;Atrophy;Brain/ pathology;Female;HIV Infections/ complications;Humans;Imaging, Three-Dimensional/methods/statistics & numerical data;Male;Middle Aged","Chiang, M. C.;Dutton, R. A.;Hayashi, K. M.;Lopez, O. L.;Aizenstein, H. J.;Toga, A. W.;Becker, J. T.;Thompson, P. M.",2007,Jan 1,10.1016/j.neuroimage.2006.08.030,0,
4941,White matter alterations in cognitively normal apoE epsilon2 carriers: insight into Alzheimer resistance?,"BACKGROUND AND PURPOSE: The basis for decreased vulnerability to AD among apoE epsilon2 carriers is unknown. The purpose of this study was to use diffusion tensor imaging to detect possible differences in white matter integrity between cognitively normal elderly apoE epsilon2 carriers and apoE epsilon3/epsilon3 controls. MATERIALS AND METHODS: Thirty-nine cognitively normal elderly individuals (19 heterozygous carriers of the apoE epsilon2 allele, 20 apoE epsilon3/epsilon3 subjects as controls) underwent diffusion tensor MR imaging on a 4T scanner. Fractional anisotropy, MD, and axial and radial diffusivity were compared using a ROI approach. In addition, an exploratory whole-brain analysis of fractional anisotropy between the 2 groups was undertaken using TBSS. RESULTS: apoE epsilon2 carriers had higher FA in the posterior cingulate white matter (P = .01) and anterior corpus callosum (P = .005) than apoE epsilon3/epsilon3 controls, secondary to lower radial diffusivity. No significant differences in the FA of the posterior corpus callosum, anterior cingulate white matter, or parahippocampal white matter were seen. Whole-brain TBSS analysis detected regions of higher FA in the apoE epsilon2 group in the superior longitudinal fasciculus, right thalamus, and the bilateral anterior limbs of the internal capsule, in addition to the posterior cingulum and corpus callosum (P < .005). There were no regions in which the apoE epsilon3/epsilon3 group had higher FA. CONCLUSIONS: apoE epsilon2 carriers harbor more robust white matter integrity that may be associated with decreased vulnerability to developing AD. This provides further evidence that regional DTI metrics may serve as early imaging biomarkers of AD risk.","Aged;Alzheimer Disease/ genetics/ pathology;Apolipoprotein E2/ genetics;Brain/ pathology/ physiopathology;Cognition Disorders/genetics/pathology;Diffusion Tensor Imaging/methods;Disease Resistance/genetics;Female;Heterozygote;Humans;Male;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Chiang, G. C.;Zhan, W.;Schuff, N.;Weiner, M. W.",2012,Aug,10.3174/ajnr.A2984,0,
4942,"Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution","BACKGROUND AND PURPOSE: Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-beta and phosphorylated tau 181 protein levels and longitudinal cognitive decline. MATERIALS AND METHODS: A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-beta levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates. RESULTS: Having >/=3 lobar microbleeds was associated with lower levels of CSF amyloid-beta (P = .001). After adjusting for CSF amyloid-beta level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations. CONCLUSIONS: The distribution of microbleeds revealed different associations with amyloid-beta and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis.",,"Chiang, G. C.;Cruz Hernandez, J. C.;Kantarci, K.;Jack, C. R., Jr.;Weiner, M. W.",2015,Sep,10.3174/ajnr.A4351,0,
4943,Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study,"Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993-1995, and returned for a repeat magnetic resonance imaging examination in 2004-2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42-5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56-6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66-4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39-4.40) and white matter lesion incidence (odds ratio 2.12; 95% confidence interval: 1.18-3.81) and progression (odds ratio 2.22; 95% confidence interval: 1.00-5.88). In conclusion, retinal microvascular abnormalities are associated with emergence of subclinical magnetic resonance imaging brain infarcts and white matter lesions, independent of shared risk factors. Retinal vascular imaging may offer a non-invasive tool to investigate the pathogenesis and natural history of cerebral small-vessel disease.",Aged;Cerebral Infarction/ diagnosis/ etiology/physiopathology;Cohort Studies;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging/methods;Male;Microvessels/ abnormalities/pathology;Middle Aged;Prospective Studies;Retinal Diseases/ complications/ diagnosis/physiopathology;Retinal Vessels/ abnormalities/pathology;Risk Factors,"Cheung, N.;Mosley, T.;Islam, A.;Kawasaki, R.;Sharrett, A. R.;Klein, R.;Coker, L. H.;Knopman, D. S.;Shibata, D. K.;Catellier, D.;Wong, T. Y.",2010,Jul,10.1093/brain/awq127,0,
4944,Cross-sectional variations of white and grey matter in older hypertensive patients with subjective memory complaints,"Mild cognitive impairment and Alzheimer's dementia involve a grey matter disease, quantifiable by (18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 +/- 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADCmean) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADCmean was variable between individuals, ranging from 0.82 to 1.01.10(- 3) mm(2) sec(- 1), and mainly in relation with CMRGlc of areas involved in Alzheimer's disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: - 0.577, p < 0.001). Both the ADCmean and CMRGlc of the interrelated grey matter areas were additionally and concordantly linked to the results of executive and memory tests and to systolic central BP (all p < 0.05). Altogether, our findings show that cross-sectional variations in overall white brain matter are linked to the metabolism of Alzheimer-like cortical areas and to cognitive performance in older hypertensive patients with only subjective memory complaints. Additional relationships with central BP strengthen the hypothesis of a contributing pathogenic role of hypertension.",Diffusion tensor imaging;Elderly;Fdg pet;Hta;Subjective memory complaint,"Chetouani, A.;Chawki, M. B.;Hossu, G.;Kearney-Schwartz, A.;Chauveau-Beuret, F.;Bracard, S.;Roch, V.;Lebon, V.;Marie, P. Y.;Benetos, A.;Joly, L.;Verger, A.",2018,,,0,
4945,Independent contribution of temporal β-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease,"The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [ (11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline. © The Author (2011).",,"Chételat, G.;Villemagne, V. L.;Pike, K. E.;Ellis, K. A.;Bourgeat, P.;Jones, G.;O'Keefe, G. J.;Salvado, O.;Szoeke, C.;Martins, R. N.;Ames, D.;Masters, C. L.;Rowe, C. C.",2011,March,,0,
4946,Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease,"The relationship between beta-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional beta-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with beta-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [(11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and beta-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical beta-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for beta-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal beta-amyloid deposition provided independent contributions to memory deficits. In contrast to global beta-amyloid deposition, temporal beta-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical beta-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to beta-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline.","Aged;Aged, 80 and over;Alzheimer Disease/ complications/pathology/radionuclide imaging;Amyloid beta-Peptides/ metabolism;Aniline Compounds;Brain/ pathology/radionuclide imaging;Brain Mapping;Carbon Radioisotopes;Cognition Disorders/complications/pathology/radionuclide imaging;Female;Humans;Imaging, Three-Dimensional/methods;Magnetic Resonance Imaging/methods;Male;Memory Disorders/ etiology/pathology/radionuclide imaging;Middle Aged;Positron-Emission Tomography/methods;Regression Analysis;Thiazoles","Chetelat, G.;Villemagne, V. L.;Pike, K. E.;Ellis, K. A.;Bourgeat, P.;Jones, G.;O'Keefe, G. J.;Salvado, O.;Szoeke, C.;Martins, R. N.;Ames, D.;Masters, C. L.;Rowe, C. C.",2011,Mar,10.1093/brain/awq383,0,
4947,Alzheimer's medical considerations,"Introduction: Alzheimer's disease is a common pathology of the modern world, especially with ageing populations. This is due to both hereditary components and as a result of numerous injuries to neuronal structures and components of the central nervous system. Therefore, research from multiple perspectives is necessary to discern the complex mechanisms that give rise to this neurodegenerative disease. One perspective is with the use of imaging, and this paper illustrates the usefulness of this approach. Methodology: The material presented in this paper addresses the issues of the etiology of Alzheimer's disease and its effects on nerve cells and changes to the central nervous system. In order to illustrate this, information relating to patients, in the form of CT images, are detailed. Results: From an analysis of the imaging tests presented in this paper, it is noted that the changes occur on the structures of the central nervous system: brain, cerebella cortical brain sharp, periventricular white matter. Beside specific changes, CT exam shows other structures, such as paranasal sinuses, mastoid cells or orbits, do undergo change. Differentiating between these structures is important for diagnosis. Conclusion: The changes taking place in relation to the central nervous system components have consequences on the patient's life. The implication is that Alzheimer's disease should be studied from different perspectives, including the studying of images to support clinical assessments. Imaging can aid the accuracy of diagnosis through the identification of specific areas and causes connection with particular types of dementia.",aged;Alzheimer disease;article;brain damage;brain radiography;brain size;brain ventricle;case report;degenerative disease;female;human;image reconstruction;lacunar stroke;neuroimaging;spiral computer assisted tomography;very elderly;white matter,"Cheşcǎ, A.;Cheşcǎ, S. A.;Sandle, T.;Babenko, D.;Azizov, I.",2016,,,0,
4948,Frontotemporal dementia versus vascular dementia: Differential features on mental status examination,"OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral (Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD. RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.",adult;aged;article;clinical feature;cognition;dementia;female;frontotemporal dementia;human;major clinical study;male;mental health;multiinfarct dementia;neuropsychological test;nuclear magnetic resonance imaging;single photon emission computer tomography,"Cherrier, M. M.;Mendez, M. F.;Ferryman, K. M.;Pachana, N. A.;Miller, B. L.;Cummings, J. L.",1997,,,0,
4949,Whole-brain CT perfusion combined with CT angiography for ischemic complications following microsurgical clipping and endovascular coiling of ruptured intracranial aneurysms,"Ischemic complications associated with microsurgical clipping and endovascular coiling affects the outcome of patients with intracranial aneurysms. We prospectively evaluated 58 intracranial aneurysm patients who had neurological deterioration or presented with poor grade (Hunt-Hess grades III and IV), aneurysm size >13 mm and multiple aneurysms after clipping or coiling. Thirty patients had ischemic complications (52%) as demonstrated by whole-brain CT perfusion (WB-CTP) combined with CT angiography (CTA). Half of these 30 patients had treatment-associated reduction in the diameter of the parent vessels (n = 6), ligation of the parent vessels or perforating arteries (n = 2), and unexplained or indistinguishable vascular injury (n = 7); seven of these 15 (73%) patients suffered infarction. The remaining 15 patients had disease-associated cerebral ischemia caused by generalized vasospasm (n = 6) and focal vessel vasospasm (n = 9); six of these 15 (40%) patients developed infarction. Three hemodynamic patterns of ischemic complications were found on WB-CTP, of which increased time to peak, time to delay and mean transit time associated with decreased cerebral blood flow and cerebral blood volume were the main predictors of irreversible ischemic lesions. In conclusion, WB-CTP combined with CTA can accurately determine the cause of neurological deterioration and classify ischemic complications. This combined approach may be helpful in assessing hemodynamic patterns and monitoring operative outcomes.",adult;aneurysm clip;aneurysm rupture;artery ligation;artery perforation;article;blood vessel diameter;blood vessel injury;blood volume;brain angiography;brain blood flow;brain infarction;brain ischemia;brain scintiscanning;cerebral blood volume;computed tomographic angiography;disease severity;endovascular aneurysm repair;female;human;Hunt Hess grade;intracranial aneurysm;major clinical study;male;mental deterioration;microsurgery;nervous system parameters;neurologic disease assessment;neuromonitoring;priority journal;prognostic assessment;prospective study;vasospasm;whole brain CT perfusion,"Cheng, X. Q.;Chen, Q.;Zhou, C. S.;Li, J. R.;Zhang, Z. J.;Zhang, L. J.;Huang, W.;Lu, G. M.",2016,,,0,
4950,Sleep disturbance correlates with white matter hyperintensity in patients with subcortical ischemic vascular dementia,"BACKGROUND: Subcortical ischemic vascular dementia (SIVD) caused by small-artery disease, and hypoperfusion is a major cause of vascular cognitive impairment. Little is known about the relationship between sleep disturbance and white matter hyperintensity (WMH). We investigated the association between sleep disturbance and WMH, measured by magnetic resonance imaging (MRI), in patients with SIVD. METHODS: Patients with SIVD recruited from our outpatient clinic completed the Sleep Disturbance Symptom Questionnaire (SDSQ) and Geriatric Depression Scale-short form (GDS-S) and underwent brain MRI. Total SDSQ scores were calculated by summing frequency ratings of the instrument's 20 items. We graded WMH on brain MR images using a visual rating scale ranging from 0 (barely detectable) to 9 (extensive changes). RESULTS: We enrolled 72 patients (31 men, 41 women; mean age, 75.9 +/- 7.9 years) with SIVD. The SDSQ scores were positively correlated with WMH grading (r = .337, P = .001) and tended to be associated with higher GDS-S scores (r = .268, P = .022). Patients with diabetes mellitus tended to display higher mean WMH severity than those without diabetes (4.2 vs 3.3, P = .022). After controlling for confounding factors, the multivariate regression model showed that WMH severity was significantly associated with sleep disturbance (P = .002). CONCLUSIONS: This study showed that manifestations of sleep disturbance were significantly associated with WMH severity, with most symptoms related to daytime hypersomnolence. Disruption of the frontal-subcortical neuronal circuit might play a role in sleep disturbance in patients with SIVD.","Aged;Aged, 80 and over;Brain/ pathology;Brain Ischemia/ complications/ psychology;Cognition/physiology;Cohort Studies;Comorbidity;Data Interpretation, Statistical;Dementia, Vascular/ complications/ psychology;Depression/psychology;Diagnostic and Statistical Manual of Mental Disorders;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Polysomnography;Sleep Wake Disorders/ pathology;Trail Making Test","Cheng, C. Y.;Tsai, C. F.;Wang, S. J.;Hsu, C. Y.;Fuh, J. L.",2013,Sep,10.1177/0891988713493503,0,
4951,Apoe gene modifies the link between type 2 diabetes and dementia risk: the memento cohort,"Background: Type 2 diabetes mellitus is associated with dementia risk, but the underlying mechanisms remain unclear. E4 isoform of the APOE gene is the strongest genetic risk factor for sporadic, late onset Alzheimer's Disease (AD), and is also associated with risk for type 2 diabetes mellitus (T2DM). In a large clinic-based prospective cohort of participants with either isolated cognitive complaints or mild cognitive impairment, we investigated whether APOE gene modifies the association between diabetes and AD risk. Methods: The Memento cohort is a multicenter longitudinal study of the determinants of cognitive evolution (including dementia) of participants consecutively enrolled in French memory clinics and presenting either isolated cognitive complaints or light to moderate cognitive impairment. Throughout France, 2323 participants have been enrolled and are followed at least five years with yearly clinical examinations and for brain imaging (MRI) every two years. All dementia cases diagnosed during follow-up are validated by an independent events'review committee. Cox proportional hazard models were used to investigate the likelihood of progression to dementia. To assess that APOE 4 modifies the association between diabetes and dementia, we tested for interaction (p<0.01) and performed stratified analyses. Results: Mean baseline age was 70.4 years, 62% were female and 40% had a clinical dementia rating scale scored 0. During a mean follow-up of 2.1 years, 160 participants became demented, 112 were of Alzheimer's type. ApoE 4 carriers were at increased risk of dementia than non-carriers [hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.83-3.90]. TD2M persons had an increased risk of incident dementia (HR=1.3, 95% CI 1.1-1.7). The highest risk of dementia was found among 4 carriers with T2DM versus 4 non-carriers without T2DM (HR 5.5, 95% CI 2.2-9.4). Trends were similar when all types of dementia were considered. Participants with T2DM and at least one 4 allele had significantly smaller hippocampal volume and higher load of white matter lesions. Conclusions: In this large naturalistic cohort, ApoE4 increases the rate of AD or dementia in those participants with T2DM. MRI markers of brain pathology show consistent results with dementia outcomes.",aged;allele;Alzheimer disease;Clinical Dementia Rating;clinical examination;clinical trial;confidence interval;controlled clinical trial;controlled study;diagnosis;disease carrier;disease course;female;follow up;France;genetic predisposition;hazard ratio;hippocampus;hospital;human;longitudinal study;major clinical study;male;memory;mild cognitive impairment;multicenter study;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;pathology;proportional hazards model;white matter lesion;apolipoprotein E;endogenous compound,"Chene, G.;Mangin, J. F.;Dubois, B.;Jean, Ousset P.;Pasquier, F.;Auriacombe, S.;Ceccaldi, M.;Blanc, F.;Gabelle, A.;Salmon, P. K.;Hugon, J.;Hanon, O.;Rouaud, O.;David, R.;Chupin, M.;Dufouil, C.",2017,,,0,
4952,Mapping the brain in type II diabetes: Voxel-based morphometry using DARTEL,"PURPOSE: To investigate the pattern of brain volume changes of the brain in patients with type II diabetes mellitus using voxel-based morphometry. MATERIAL AND METHODS: Institutional ethics approval and informed consent were obtained. VBM based on the high resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images was obtained from 16 type II diabetes patients (mean age 61.2 years) and 16 normal controls (mean age 59.6 years). All images were spatially preprocessed using Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) algorithm, and the DARTEL templates were made from 100 normal subjects. Statistical parametric mapping was generated using analysis of covariance (ANCOVA). RESULTS: An atrophy pattern of gray matter was seen in type II diabetes patients compared with controls that involved the right superior, middle, and inferior temporal gyri, right precentral gyrus, and left rolandic operculum region. The loss of white matter volume in type II diabetes mellitus was observed in right temporal lobe and left inferior frontal triangle region. ROI analysis revealed that the gray and white matter volume of right temporal lobe were significant lower in type II diabetes mellitus than that in controls (P<0.05). CONCLUSION: This work demonstrated that type II diabetes mellitus patients mainly exhibited gray and white matter atrophy in right temporal lobe, and this finding supported that type II diabetes mellitus could lead to subtle diabetic brain structural changes in patients without dementia or macrovascular complications.","Aged;Brain/ pathology;Diabetes Mellitus, Type 2/ pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Reproducibility of Results;Sensitivity and Specificity","Chen, Z.;Li, L.;Sun, J.;Ma, L.",2012,Aug,10.1016/j.ejrad.2011.04.025,0,
4953,Neuroimaging indicators of the performance of instrumental activities of daily living in Alzheimer's disease combined with cerebrovascular disease,"OBJECTIVES: The aim of the present study was to explore the magnetic resonance imaging correlates of the performance of instrumental activities of daily living (IADL) in patients with Alzheimer's disease combined with cerebrovascular disease. METHODS: A total of 66 patients with Alzheimer's disease combined with cerebrovascular disease formed the study sample. Two regression models were constructed to find correlates of IADL. Model 1 only included clinical variables and model 2 included both clinical and magnetic resonance imaging variables. RESULTS: In model 1, with IADL as the dependent variable, the Mini-Mental State Examination (MMSE) score, Physical Self-Maintenance Scale score at baseline and age were significant correlates accounting for 40.1% of the variance of IADL at baseline. MMSE score and age were also significant correlates of IADL at 6 months, accounting for 38.1% of the variance of it. In model 2, severity of white matter lesions, MMSE and Physical Self-Maintenance Scale scores at baseline significantly correlated with IADL at baseline, accounting for 52.1% of the variance of the dependent variables; severity of white matter lesions and MMSE significantly correlated with IADL at 6 months, accounting for 41.5% of the variance of the dependent variables. CONCLUSION: In patients with Alzheimer's disease combined with cerebrovascular disease, subcortical ischemic lesions might be significant contributor to the functional status.",Activities of Daily Living;Aged;Alzheimer Disease/complications/ physiopathology;Cerebrovascular Disorders/complications/ physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Neuroimaging,"Chen, Y. K.;Xiao, W. M.;Li, W. Y.;Liu, Y. L.;Li, W.;Qu, J. F.;Fang, X. W.;Weng, H. Y.;Ungvari, G. S.;Xiang, Y. T.",2015,May,10.1111/ggi.12323,0,
4954,A semi-quantitative method for correlating brain disease groups with normal controls using SPECT: Alzheimer's disease versus vascular dementia,"PURPOSE: To demonstrate the utility of semi-quantitative circumferential-profile analysis of regional cerebral blood flow (rCBF) SPECT in Alzheimer's disease (AD) versus white matter vascular dementia (WM-VaD). METHODS: Subjects underwent dementia evaluation, MRI and Tc-99m HMPAO SPECT. rCBF patterns from 11 AD and 20 WM-VaD patients were compared to 17 controls using semi-quantitative circumferential-profile analysis. RESULTS: AD patients showed more significant semi-quantitative circumferential-profile reductions in the posterior temporo-parietal regions, whereas WM-VaD patients demonstrated greater reductions involving the frontal regions of the brain. CONCLUSION: Semi-quantitative circumferential-profile analysis provides a practical semi-quantitative method to evaluate brain SPECT scans in AD versus WM-VaD patients.","Aged;Alzheimer Disease/*radionuclide imaging;Case-Control Studies;Cerebrovascular Circulation;Dementia, Vascular/*radionuclide imaging;Female;Humans;Image Processing, Computer-Assisted/*methods;Linear Models;Magnetic Resonance Imaging;Male;Radiopharmaceuticals;Retrospective Studies;Statistics, Nonparametric;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/*methods","Chen, Y. J.;Deutsch, G.;Satya, R.;Liu, H. G.;Mountz, J. M.",2013,Jan,10.1016/j.compmedimag.2012.11.001,0,
4955,"Regional quantification of white matter hyperintensity in normal aging, mild cognitive impairment, and Alzheimer's disease","BACKGROUND/AIMS: A quantitative method was applied to measure the volume of white matter hyperintensity (WMH) in different brain regions of subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal healthy age-matched controls, and the relationship between regional WMH and age and cognitive function was investigated. METHODS: Fifty-six subjects were included in this study, 27 AD, 15 MCI and 14 normal age-matched controls. A user-friendly software was developed for WMH quantification in frontal, temporal, and parieto-occipital lobes. Mini-Mental State Examination and cognitive scores in performing naming, language fluency, and memory tasks were obtained for correlation analysis. RESULTS: AD patients had the greatest total WMH volume, followed by MCI, then controls. However, there was a large variation within each group, and the difference did not reach a significant level. There was a positive linear correlation between the total WMH (p = 0.031) and the frontal WMH (p = 0.006) vs. age. After age correction the Boston Naming Test scores were negatively correlated with the total WMH volume in the AD (p = 0.03) and the control (p = 0.03) groups, and with the frontal WMH in controls (p = 0.01). CONCLUSION: We demonstrated a quantitative analysis method to measure regional WMH. Although WMH was not strongly associated with disease severity or cognition, it may provide a characteristic neuroimaging parameter in the study of AD development.","Aged;Aging/*pathology/psychology;Alzheimer Disease/*pathology/psychology;Brain/*pathology;Cognition/physiology;Cognition Disorders/*pathology/psychology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory/physiology;Neuropsychological Tests;Psychomotor Performance/physiology;Verbal Behavior","Chen, Y. F.;Wang, H.;Chu, Y.;Huang, Y. C.;Su, M. Y.",2006,,10.1159/000094785,0,
4956,Exploring the Spectrum of Subcortical Hyperintensities and Cognitive Decline,"White matter hyperintensities (WMHs) include periventricular WMH (pvWMH) and deep WMH. When hyperintensities in the basal ganglia or brainstem are included, the collective term is subcortical hyperintensities. Both WMH and medial temporal lobe atrophy (MTA) are risk factors for cognitive decline. This prospective study enrolled participants aged 50-85 years and followed their neuropsychological assessments annually for 2 years to explore the interactive effects of WMH and MTA on longitudinal clinical decline. Brain MRI was performed at the beginning of enrollment. Of the 200 participants, 57 were ""normal"" individuals, 40 had dysexecutive mild cognitive impairment, 53 had amnestic mild cognitive impairment, and 50 had Alzheimer's disease (AD). Overall, MTA significantly correlated with pvWMH (p=0.0004) but not with deep WMH, as defined by criteria using the Scheltens' Scale. Total Scheltens' score was specifically associated with the domain of semantic fluency (beta=-0.4, 95% CI=-0.7 to -0.2, p=0.002), which remained significant when adjusting for MTA (beta=-0.3, 95% CI=-0.5 to -0.1, p=0.017). The pvWMH was significantly higher in AD subjects than in normal control subjects (beta=0.3, 95% CI=0.1 to 0.4, p=0.001), especially the periventricular occipital caps (beta=0.2, 95% CI=0.1 to 0.3, p=0.0003). Cox proportional hazards model showed that the periventricular bands (PVB) predicted 1-year clinical decline (hazard ratio [HR]=5.3, 95% CI=1.8 to 15.7, p=0.002), which remained significant when further adjusting for MTA (HR=4.0, 95% CI=1.3 to 12.1, p=0.013). In summary, pvWMH, especially the occipital caps, was correlated with MTA and the AD subgroup. Assessment of semantic fluency may be useful for the clinical evaluation of the degree of subcortical hyperintensity burden. Visual rating of PVB could be an independent predictor for 1-year clinical decline.",Alzheimer's disease;White matter hyperintensity;medial temporal lobe atrophy;mild cognitive impairment,"Chen, Y. C.;Tsao, H. H.;Chu, Y. C.;Wang, J. J.;Lee, J. D.;Chang, P. Y.;Hsu, W. C.",2017,Oct 24,,0,
4957,Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL),"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small vessel diseases caused by a mutation in the NOTCH3 gene. The clinical manifestations of CADASIL range from single or multiple lacunar infarcts, transient ischemic attacks, dementia, migraine with aura to psychiatric disorders. The features of brain MRI of CADASIL include multiple lacunar infarcts and diffuse leukoencephalopathy, which frequently involves external capsules and anterior temporal regions. Almost all patients with CADASIL harbor cysteine-involving mutations in NOTCH3. In Taiwan, , two thirds of CADASIL patients carry NOTCH3 p.R544C mutations, and only approximately 56% of patients with CADASIL have leukoencephalopathy with anterior temporal regions involvement.",Notch3 receptor;article;CADASIL;clinical feature;external capsule;gene mutation;human;neuroimaging;nuclear magnetic resonance imaging;temporal lobe,"Chen, Y. C.;Hsiao, C. T.;Soong, B. W.;Lee, Y. C.",2014,,,0,
4958,Aberrant functional networks connectivity and structural atrophy in silent lacunar infarcts: relationship with cognitive impairments,"Silent or asymptomatic lacunar infarcts (LACI) are common in elderly individuals, but it remains largely unclear how these often neglected silent brain infarcts lead to multiple domain cognitive deficits and even Alzheimer's disease (AD). In this study, we investigated the difference between patients with silent LACI in basal ganglia region and healthy controls for the structural and functional changes in the aspects of alterations of gray matter (GM) volume and intra-/inter-default mode network (DMN) and salience network (SN) connectivity. Thirty patients with silent LACI in the basal ganglia region and thirty healthy controls participated in the study. Voxel-based morphometry analysis was employed to measure the GM volume. We further investigated the intra/inter-network connectivity of DMN and SN using resting-state functional magnetic resonance imaging. Compared with healthy controls, patients performed worse in cognitive function in the aspects of general mental status, attention, and memory. The LACIs showed more severe GM atrophy in insula, anterior cingulate cortex, caudate, and superior temporal pole than controls. The connectivity within and between two networks was also reduced in patients. Importantly, the disrupted connectivity correlated with the patients' cognitive performance. Our findings support the hypothesis that silent lacunar infarcts result in cognitive decline, GM, and functional connectivity loss.","Aged;Atrophy/etiology;Basal Ganglia/blood supply/ pathology;Cognition Disorders/ etiology;Female;Gray Matter/blood supply/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Models, Neurological;Neural Pathways/blood supply/ pathology;Neuropsychological Tests;Oxygen/blood;Principal Component Analysis;Statistics as Topic;Stroke, Lacunar/ complications/ pathology","Chen, Y.;Wang, J.;Zhang, J.;Zhang, T.;Chen, K.;Fleisher, A.;Wang, Y.;Zhang, Z.",2014,,10.3233/jad-140948,0,
4959,Association of white matter integrity and cognitive functions in patients with subcortical silent lacunar infarcts,"BACKGROUND AND PURPOSE: Silent lacunar infarct (SLI) is a risk factor for dementia. This study investigated the white matter integrity abnormality and its relationship to the cognition impairments in SLI patients. METHODS: Between 27 patients with SLI in basal ganglia and 30 healthy controls, we assessed the difference in a batter of neuropsychological tests and in white matter integrity measurements, fractional anisotropy, and mean diffusivity, using tract-based spatial statistics. RESULTS: Compared with healthy controls, SLI patients performed worse in general mental status, memory, executive function, and language ability. They also had reduced fractional anisotropy and increase mean diffusivity in brain regions such as the body and genu of corpus callosum, the forceps minor, the bilateral superior and bilateral anterior corona radiate, and the left external capsule. Furthermore, we found that in SLI patients, fractional anisotropy measure in left external capsule was positively correlated to the performance in memory and language ability. CONCLUSIONS: SLI in basal ganglia leads to local and remote white matter integrity damages and to the cognition impairments.","Aged;Anisotropy;Basal Ganglia Diseases/pathology/physiopathology;Cognition Disorders/pathology/physiopathology;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Stroke, Lacunar/pathology/physiopathology;White Matter/pathology/physiopathology","Chen, Y.;Wang, A.;Tang, J.;Wei, D.;Li, P.;Chen, K.;Wang, Y.;Zhang, Z.",2015,Apr,10.1161/strokeaha.115.008998,0,
4960,Automated detection of pathologic white matter alterations in Alzheimer's disease using combined diffusivity and kurtosis method,"Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) are important diffusion MRI techniques for detecting microstructure abnormities in diseases such as Alzheimer's. The advantages of DKI over DTI have been reported generally; however, the indistinct relationship between diffusivity and kurtosis has not been clearly revealed in clinical settings. In this study, we hypothesize that the combination of diffusivity and kurtosis in DKI improves the capacity of DKI to detect Alzheimer's disease compared with diffusivity or kurtosis alone. Specifically, a support vector machine-based approach was applied to combine diffusivity and kurtosis and to compare different indices datasets. Strict assessments were conducted to ensure the reliability of all classifiers. Then, data from the optimized classifiers were used to detect abnormalities. With the combination, high accuracy performances of 96.23% were obtained in 53 subjects, including 27 Alzheimer's patients. More highly scored abnormal regions were selected by the combination than alone. The results revealed that more precise diffusivity and complementary kurtosis mainly contributed to the high performance of the combination in DKI. This study provides further understanding of DKI and the relationship between diffusivity and kurtosis in pathologic white matter alterations in Alzheimer's disease.",Aged;Alzheimer Disease/ diagnostic imaging/ pathology;Diffusion Tensor Imaging/ methods;Female;Humans;Leukoaraiosis/diagnostic imaging/pathology;Male;Middle Aged;Reproducibility of Results;Support Vector Machine;White Matter/ diagnostic imaging/ pathology;Alzheimer's disease;Diffusion kurtosis imaging;Diffusion tensor imaging;Diffusional MRI;Machine learning,"Chen, Y.;Sha, M.;Zhao, X.;Ma, J.;Ni, H.;Gao, W.;Ming, D.",2017,Jun 30,,0,
4961,Frontal lobe atrophy is associated with small vessel disease in ischemic stroke patients,"BACKGROUND: The pathogenesis of frontal lobe atrophy (FLA) in stroke patients is unclear. We aimed to ascertain whether subcortical ischemic changes were more associated with FLA than with parietal lobe atrophy (PLA) and temporal lobe atrophy (TLA). METHODS: Brain magnetic resonance images (MRIs) from 471 Chinese ischemic stroke patients were analyzed. Lobar atrophy was defined by a widely used visual rating scale. All patients were divided into non-severe, mild-moderate, and severe atrophy of the frontal, parietal, and temporal lobe groups. The severity of white matter lesions (WMLs) was rated with the Fazekas' scale. Clinical and radiological features were compared among the groups. Subsequent logistic regressions were performed to determine the risk factors of atrophy and severe atrophy of the frontal, parietal and temporal lobes. RESULTS: The frequency of FLA in our cohort was 36.9% (174/471). Severe FLA occurred in 30 (6.4%) patients. Age, previous stroke, and periventricular hyperintensities (PVH) (odds ratio (OR)=1.640, p=0.039) were independent risk factors of FLA. Age and deep white matter hyperintensities (DWMH) (OR=3.634, p=0.002) were independent risk factors of severe FLA. PVH and DWMH were not independent risk factors of PLA and TLA. CONCLUSION: Frontal lobe atrophy in ischemic stroke patients may be associated with small vessel disease. The association between WMLs and FLA was predominant over atrophy of the parietal and temporal lobes, which suggests that the frontal lobe may be vulnerable to subcortical ischemic changes.","Aged;Atrophy;Brain Ischemia/ pathology/psychology;Capillaries/pathology;Cerebral Arterial Diseases/pathology;Cerebral Infarction/pathology;Dementia, Vascular/pathology/psychology;Female;Frontal Lobe/ pathology;Humans;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Parietal Lobe/pathology;Retrospective Studies;Risk Factors;Stroke/ pathology/psychology;Temporal Lobe/pathology","Chen, Y.;Chen, X.;Xiao, W.;Mok, V. C.;Wong, K. S.;Tang, W. K.",2009,Dec,10.1016/j.clineuro.2009.08.019,0,
4962,Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE varepsilon4 allele,"As the Apolipoprotein E (APOE) varepsilon4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal varepsilon4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal varepsilon4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For varepsilon4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE varepsilon4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in varepsilon4 carriers. Our results demonstrated varepsilon4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.",Aged;Alleles;Apolipoprotein E4/*genetics;Brain/*pathology/*physiopathology;Brain Mapping;Cholesterol/blood;Diffusion Tensor Imaging;Female;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology/physiopathology;Neuropsychological Tests;ROC Curve;Rest;White Matter/*pathology/*physiopathology,"Chen, Y.;Chen, K.;Zhang, J.;Li, X.;Shu, N.;Wang, J.;Zhang, Z.;Reiman, E. M.",2015,Apr,10.1038/npp.2014.302,0,
4963,Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ε4 allele,"As the Apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ε4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ε4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ε4 carriers, we found reduced global efficiency significantly in",,"Chen, Y.;Chen, K.;Zhang, J.;Li, X.;Shu, N.;Wang, J.;Zhang, Z.;Reiman, E. M.",2014,1,,0,
4964,White matter abnormalities revealed by diffusion tensor imaging in non-demented and demented HIV+ patients,"HIV associated dementia (HAD) is the most advanced stage of central nervous system disease caused by HIV infection. Previous studies have demonstrated that patients with HAD exhibit greater cerebral and basal ganglia atrophy than non-demented HIV+ (HND) patients. However, the extent to which white matter is affected in HAD patients compared to HND patients remains elusive. This study is designed to address the potential white matter abnormalities through the utilization of diffusion tensor imaging (DTI) in both HND and HAD patients. DTI and T1-weighted images were acquired from 18 healthy controls, 21 HND and 8 HAD patients. T1 image-based registration was performed to 1) parcellate the whole brain white matter into major white matter regions, including frontal, parietal, temporal and occipital white matter, corpus callosum and internal capsule for statistical comparisons of the mean DTI values, and 2) warp all DTI parametric images towards the common template space for voxel-based analysis. The statistical comparisons were performed with four DTI parameters including fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivities. With Whitney U tests on the mean DTI values, both HND and HAD demonstrated significant differences from the healthy control in multiple white matter regions. In addition, HAD patients exhibited significantly elevated MD and RD in the parietal white matter when compared to HND patients. In the voxel-based analysis, widespread abnormal regions were identified for both HND and HAD patients, although a much larger abnormal volume was observed in HAD patients for all four DTI parameters. Furthermore, both region of interest (ROI) based and voxel-based analyses revealed that RD was affected to a much greater extent than AD by HIV infection, which may suggest that demyelination is the prominent disease progression in white matter.","Adult;Dementia/ complications/ pathology;Demyelinating Diseases/ complications/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;HIV Infections/ complications/ pathology;Humans;Male;Nerve Fibers, Myelinated/ pathology","Chen, Y.;An, H.;Zhu, H.;Stone, T.;Smith, J. K.;Hall, C.;Bullitt, E.;Shen, D.;Lin, W.",2009,Oct 1,10.1016/j.neuroimage.2009.04.030,0,
4965,Clinical research on treating senile dementia by combining acupuncture with acupoint-injection,"Combining acupuncture with acupoint-injection of aceglutamidi has been used in treating 38 cases of senile dementia. Our experiment showed that the therapy is effective for the cases of multi-infarct dementia, the rate of success being 42.85% and of improvement 42.86%, the total efficacy rate being 85.71%. The rating was based on the revised Hasegawa Dementia Scale and the Functional Activity Questionnaire. In addition, it has been observed that the component of high density lipid-cholesterone increased significantly after treatment.",Hs-precntrl: sr-compmed: hs-handsrch,"Chen, Y.",1992,,,0,
4966,Application of ischemic score of Hachinski in differentiation of multi-infarct dementia,"The Beijing Geriatric Mental Health Center has admitted 46 cases of dementia of the aged in recent more than two years. For them many routine examinations as well as rating scale related and CT scanning were carried out. Their final diagnosis at discharge were of 4 categories: (1) Multi-infarct dementia (MID); (2) Alzheimer's disease(AD); (3) MID+AD, mixed type; and (4) dementia of other causes. We applied Ischemic Score of Hachinski for the 14 cases of MID. The score was over 7 points in all the 14 cases. And the CT pictures in 11 cases showed multiple infarctions, only 3 cases gave evidence of cerebral atrophy. Therefore, the Ischemic Score and CT Scanning were very significant in the diagnosis of MID. The role of each item of the total 13 items of the ischemic score in the diagnosis of MID was discussed according to the clinical materials. It is pointed out that the ""stepwise deterioration"", ""fluctuating course"", ""history of strokes"" and ""focal neurological signs"" were more important in the diagnosis of MID.",Alzheimer disease;article;computer assisted tomography;dementia;differential diagnosis;human;multiinfarct dementia;radiography,"Chen, X. S.",1992,,,0,
4967,Extraction of dynamic functional connectivity from brain grey matter and white matter for MCI classification,"Brain functional connectivity (FC) extracted from resting-state fMRI (RS-fMRI) has become a popular approach for diagnosing various neurodegenerative diseases, including Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Current studies mainly construct the FC networks between grey matter (GM) regions of the brain based on temporal co-variations of the blood oxygenation level-dependent (BOLD) signals, which reflects the synchronized neural activities. However, it was rarely investigated whether the FC detected within the white matter (WM) could provide useful information for diagnosis. Motivated by the recently proposed functional correlation tensors (FCT) computed from RS-fMRI and used to characterize the structured pattern of local FC in the WM, we propose in this article a novel MCI classification method based on the information conveyed by both the FC between the GM regions and that within the WM regions. Specifically, in the WM, the tensor-based metrics (e.g., fractional anisotropy [FA], similar to the metric calculated based on diffusion tensor imaging [DTI]) are first calculated based on the FCT and then summarized along each of the major WM fiber tracts connecting each pair of the brain GM regions. This could capture the functional information in the WM, in a similar network structure as the FC network constructed for the GM, based only on the same RS-fMRI data. Moreover, a sliding window approach is further used to partition the voxel-wise BOLD signal into multiple short overlapping segments. Then, both the FC and FCT between each pair of the brain regions can be calculated based on the BOLD signal segments in the GM and WM, respectively. In such a way, our method can generate dynamic FC and dynamic FCT to better capture functional information in both GM and WM and further integrate them together by using our developed feature extraction, selection, and ensemble learning algorithms. The experimental results verify that the dynamic FCT can provide valuable functional information in the WM; by combining it with the dynamic FC in the GM, the diagnosis accuracy for MCI subjects can be significantly improved even using RS-fMRI data alone. Hum Brain Mapp 38:5019-5034, 2017. (c) 2017 Wiley Periodicals, Inc.",Alzheimer's disease;functional connectivity;functional correlation tensor;mild cognitive impairment;resting-state fMRI,"Chen, X.;Zhang, H.;Zhang, L.;Shen, C.;Lee, S. W.;Shen, D.",2017,Oct,,0,
4968,"Prevalence, incidence, and risk factors of lacunar infarcts in a community sample","BACKGROUND: Lacunar infarcts are small cavitated lesions no larger than 2 cm in diameter. Although often asymptomatic, they have been suggested as an important pathologic substrate of vascular dementia. The prevalence and risk factor profile of lacunar infarction has been variously reported, but the incidence data are scarce for large community-based data. METHODS: Participants (n = 477) were recruited randomly from the electoral roll of community residents aged 60-64 years as part of the PATH Through Life Study. Demographic information and risk factor data were collected and MRI brain scans performed in two waves, 4 years apart. The number and locations of lacunar infarcts as well as other volumetric data were assessed on T1-weighted and T2-weighted fluid-attenuated inversion recovery images. RESULTS: In wave 1, 37 (7.8%) participants had at least one lacunar infarct. New lacunar infarcts were detected in 6 (6/375, 1.6%) participants at wave 2. Lacunes present at wave 1 increased significantly in mean volume from 53.90 to 69.86 mm over 4 years. Hypertension (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.01-2.60), anterior ventricle-brain ratio (%) (OR = 1.02; CI = 1.003-1.036), and volume of white matter hyperintensities (OR = 4.9; CI = 1.53-15.80) were independently associated with the prevalence of lacunar infarction. CONCLUSION: Lacunes were common incidental findings in the brains of individuals in their 60s, and their prevalence as well as size increased with age. Hypertension was the major treatable risk factor, and lacunar infarction was usually associated with severe white matter hyperintensities on T2-weighted imaging. © 2009 AAN Enterprises, Inc.",,"Chen, X.;Wen, W.;Anstey, K. J.;Sachdev, P. S.",2009,July,,0,
4969,Predictors for vascular cognitive impairment in stroke patients,"BACKGROUND: Around two thirds stroke patients may suffer from vascular cognitive impairment (VCI). Our previous study has validated the NINDS-CSN harmonization standard for VCI diagnosis in Chinese. In this study, we aimed to investigate the predictors for VCI in Chinese post-stroke patients. METHODS: We compared epidemiological, clinical, and neuroimaging data (number, size and location of acute infarcts and lacunes, severities of white matter hyperintensities and brain atrophy) between stroke patients with and without VCI. Univariate and logistic regression analyses were utilized to determine VCI predictors. RESULTS: Fifty-six consecutive patients (age, 63.8 +/- 8.3 years; female, 37.5%) were recruited at a mean interval of 7.1 months after stroke onset, and 31 (55.4%) patients were diagnosed with VCI based on a validated 60-min neuropsychological battery. VCI patients were older (p = 0.023), less educated (p = 0.001), more likely to be female (p < 0.001), had a recurrent stroke (p = 0.028), and described higher apathy (p = 0.022) and worse pre-stroke cognition (p = 0.048) than cognitively normal patients. Lower educational level (adjusted odds ratio [OR] 0.750, 95% confidence interval [CI], 0.573-0.981; p = 0.035), female sex (adjusted OR 8.288, 95% CI, 1.522-45.113; p = 0.014), recurrent stroke (adjusted OR 11.327, 95% CI, 1.335-96.130, p = 0.026), and global cortical atrophy (adjusted OR 5.730, 95% CI, 1.128-29.101, p = 0.035) were independently associated with VCI in post-stroke patients. CONCLUSIONS: Lower education, female sex, recurrent stroke and global cortical atrophy were associated with VCI in Chinese stroke patients.","Age Factors;Aged;Apathy;Atrophy;Brain/pathology;Cerebral Infarction/etiology;Cognitive Dysfunction/ etiology;Dementia, Vascular/etiology;Educational Status;Female;Follow-Up Studies;Humans;Hypertension/complications;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuroimaging/methods;Neuropsychological Tests;Recurrence;Sex Factors;Smoking;Stroke/ complications;Lacune;Neuropsychology;Stroke;Vascular cognitive impairment;White matter hyperintensities","Chen, X.;Duan, L.;Han, Y.;Tian, L.;Dai, Q.;Wang, S.;Lin, Y.;Xiong, Y.;Liu, X.",2016,Jul 26,,0,
4970,Adult cerebral adrenoleukodystrophy and Addison's disease in a female carrier,We described a 38-year-old woman of rapidly progressive dementia with white matter encephalopathy and death. She had Addison's disease but the adrenal glands were hyperplastic. Brain magnetic resonance imaging revealed diffuse white matter lesion predominantly in the frontal lobe with band-like contrast enhancement. l-Methyl-11C-methionine positron emission tomography revealed accumulation of tracer in bilateral frontal lobes. Stereotactic biopsy demonstrated demyelination changes. A number of urinary organic acids were elevated. Adrenoleukodystrophy was diagnosed by elevated plasma very long chain fatty acid and ABCD1 gene mutation (C1544C/T). Adrenoleukodystrophy should be considered as a differential diagnosis in women with rapidly progressive white matter encephalopathy. © 2014 Elsevier B.V.,,"Chen, X.;Chen, Z.;Huang, D.;Liu, X.;Gui, Q.;Yu, S.",2014,10,,0,
4971,Relationship between MRI features of acute cerebral infarction and developing vascular dementia,"Objective To study the relationship between the MRI features of acute cerebral infarction (ACI) and developing vascular dementia ( VD). Methods The patients who had ACI history more than 6 months were divided into vascular dementia group and no vascular dementia group by MMSE and CDR evaluations. The MRI data of acute stoke of the two groups were reviewed and analyzed retrospectively. Results In VD group the happenings of infaction at subcortex of lobus frontalis, subcortex of lobus temporalis, anterior capsula interna, knee of capsula lnterna, nucleus caudatus and thalamus were more than those in no vascular dementia group (P < 0.05 ∼0. 01). infactions involved more than 3 positions in VD group were also more than that in no vascular dementia group (P< Q.OS). Degree 3 of LA was 35. 0% in VD group and 10. 0% in no vascular dementia group, there was a significant difference between the two groups ( P < 0. 05 ). The incidence rates of LA in corona radiata and basal ganglia in ACI group were significantly higher than those in no vascular dementia group ( P < 0. 05). The MRI linearity index of brain atrophy ( hippocampi interuncal distance and ventricular index) between VD group and no vascular group was significamly different ( P<0. 05 -0.01). Conclusions The infarctions in subcortex of lobus frontalis, subcortex of lobus temporalis, anterior capsula interna, knee of capsula interna, nucleus caudatus and thalamus, at the same time ,infarction involved more than 3 positions, degree 3 of LA, LA in corona radiata and basal ganglia, hippocampi interuncal distance and ventricular index may be used as predictable index of developing VD in ACI patients.",basal ganglion;brain atrophy;brain infarction;capsula interna;caudate nucleus;frontal lobe;hippocampus;human;incidence;infarction;knee;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;patient;subcortex;temporal lobe;thalamus,"Chen, W. P.;Li, J. R.;Xu, S. W.",2008,,,0,
4972,"Assessment of the Virchow-Robin Spaces in Alzheimer disease, mild cognitive impairment, and normal aging, using high-field MR imaging","BACKGROUND AND PURPOSE: VRSs are the perivascular spaces surrounding the deep perforating arteries in the brain. Although VRS variations with age and disease pathologies have been reported previously, the radiologic characteristics of the VRS in relation to AD are poorly understood. This study investigated the prevalence, spatial distribution, and severity of the VRS in AD, MCI, and older adults who were CN. It also investigated the relationship of the VRS to white matter changes. MATERIALS AND METHODS: Structural MR imaging data were acquired from 158 participants (AD = 37, MCI = 71, CN = 50, mean age = 74.97 +/- 7.20 years) who had undergone T1WI at 3T. The severity of VRS in the white matter, basal ganglia, hippocampus, and brain stem structures was evaluated by using a semiquantitative scale, adapted from existing rating scales. A VRS total score summarizing the subscales was calculated to assess the whole-brain VRSs. RESULTS: VRSs were observed in multiple brain regions of all participants, typically presented as <2-mm well-margined symmetric round-, oval- and linear-shaped hypointensities on T1WI. The VRS total score increased with leukoaraiosis, atrophy, and advanced age (P < .001). Individuals with AD and MCI showed greater levels of VRS than control subjects. The VRS total score discriminated individuals with AD and those who were CN with an accuracy of 0.79 (95% CI, 0.69-0.89). CONCLUSIONS: VRSs are common in older adults and are more severe in AD and MCI than in CN. Whether increased VRSs can be reliably used to aid in AD diagnosis warrants further investigation.",Aged;Aging;Alzheimer Disease/ pathology;Brain/ anatomy & histology/ pathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Mild Cognitive Impairment/ pathology,"Chen, W.;Song, X.;Zhang, Y.",2011,Sep,10.3174/ajnr.A2541,0,
4973,Acute parietal lobe infarction presenting as Gerstmann's syndrome and cognitive decline mimicking senile dementia,"Gerstmann's syndrome encompasses the tetrad of finger agnosia, agraphia, acalculia, and right-left confusion. An elderly man with a history of several cardiovascular diseases was initially brought to the psychiatric outpatient department by his family because of worsening of recent memory, executive function, and mixed anxious-depressive mood. Gerstmann's syndrome without obvious motor function impairment and dementia-like features could be observed at first. Emergent brain computed tomography scan revealed new left-middle cerebral artery infarction over the left posterior parietal lobe. This case reminds us that acute cerebral infarction involving the parietal lobe may present as Gerstmann's syndrome accompanied by cognitive decline mimicking dementia. As a result, emergent organic workups should be arranged, especially for elderly patients at high risk for cerebral vascular accident.",Gerstmann's syndrome;dementia;parietal lobe infarction,"Chen, T. Y.;Chen, C. Y.;Yen, C. H.;Kuo, S. C.;Yeh, Y. W.;Chang, S.;Huang, S. Y.",2013,,10.2147/ndt.s43527,0,
4974,Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias,"White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n=10), Alzheimer's disease (AD, n=30), subcortical ischemic vascular dementia (SIVD, n=18), frontotemporal dementia (FTD, n=7), and control subjects (n=20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.","Aged;Aged, 80 and over;Alzheimer Disease/pathology;Amnesia/ pathology/psychology;Brain/ pathology;Brain Mapping/methods;Cognition Disorders/ pathology/psychology;Corpus Callosum/pathology;Dementia/classification/ pathology/psychology;Dementia, Vascular/pathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Severity of Illness Index","Chen, T. F.;Lin, C. C.;Chen, Y. F.;Liu, H. M.;Hua, M. S.;Huang, Y. C.;Chiu, M. J.",2009,Jul 15,10.1016/j.pscychresns.2008.09.002,0,
4975,Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease,"Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal-related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Analysis of Variance;Anisotropy;Brain Mapping;Cerebral Ventricles/ pathology;Cognition Disorders/ pathology/physiopathology;Dementia/ pathology/physiopathology;Diffusion Magnetic Resonance Imaging/methods;Executive Function/ physiology;Female;Humans;Imaging, Three-Dimensional/methods;Male;Middle Aged;Neuropsychological Tests;Statistics as Topic","Chen, T. F.;Chen, Y. F.;Cheng, T. W.;Hua, M. S.;Liu, H. M.;Chiu, M. J.",2009,Nov,10.1002/hbm.20810,0,
4976,Diffusion tensor imaging of the brain in patients with Alzheimer's disease and cerebrovascular lesions,"BACKGROUND: Recent autopsy study showed a high incidence of cerebrovascular lesions in Alzheimer's disease (AD). To assess the impact of cerebrovascular pathology in AD, we used diffusion tensor imaging (DTI) to study AD patients with and without cerebrovascular lesions. MATERIALS AND METHODS: Conventional and DTI scans were obtained from 10 patients with probable AD, 10 AD/V patients (probable AD with cerebrovascular lesions) and ten normal controls. Mean diffusivity (D) and fractional anisotropy (FA) values of some structures involved with AD pathology were measured. RESULTS: D value was higher in AD patients than in controls in hippocampus and the cingulate gyrus. In AD/V patients, increased D value was found in the same structures and also in the thalamus and basal ganglia compared to controls. There was a significant difference of D value between AD and AD/V patients. FA value reduced in the white matter of left inferior temporal gyrus and in the bilateral middle cingulate gyrus in patients with AD/V compared with controls. The MMSE (mini-mental state examination) score significantly correlated with FA value in the right hippocampus (r=0.639, P<0.019), in the right anterior cingulate gyrus (r=0.587, P<0.035) and in left parahippocampal gyrus (r=0.559, P<0.047). CONCLUSION: Cerebrovascular pathology had stronger impact on the D value than the AD pathology alone did. Elevated D value in thalamic and basal ganglia may contribute to cognitive decline in AD/V patients. Reduced FA values in AD/V patients may indicate that cerebrovascular pathology induced more severe white matter damage than the AD pathology alone did.",Aged;Alzheimer Disease/complications/ pathology;Brain/blood supply/pathology;Cerebral Cortex/pathology;Cerebrovascular Disorders/complications/ pathology;Cognition;Corpus Callosum/pathology;Diffusion Magnetic Resonance Imaging;Female;Hippocampus/pathology;Humans;Male;Temporal Lobe/pathology,"Chen, S. Q.;Kang, Z.;Hu, X. Q.;Hu, B.;Zou, Y.",2007,Apr,10.1631/jzus.2007.B0242,0,
4977,White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study,"BACKGROUND: Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period. METHODS: Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression. RESULTS: Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time. CONCLUSIONS: Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.","Aged;Antidepressive Agents/therapeutic use;Brain/ pathology;Brain Damage, Chronic/ diagnosis/drug therapy;Dementia, Vascular/ diagnosis/drug therapy;Depressive Disorder, Major/ diagnosis/drug therapy;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mathematical Computing;Middle Aged;Treatment Outcome","Chen, P. S.;McQuoid, D. R.;Payne, M. E.;Steffens, D. C.",2006,Sep,10.1017/s1041610205002796,0,
4978,Cognitive severity-specific neuronal degenerative network in charcoal burning suicide-related carbon monoxide intoxication,"While carbon monoxide (CO) intoxication often triggers multiple intraneuronal immune- or inflammatory-related cascades, it is not known whether the pathological processes within the affected regions evolve equally in the long term. To understand the neurodegenerative networks, we examined 49 patients with a clinical diagnosis of CO intoxication related to charcoal burning suicide at the chronic stage and compared them with 15 age- and sex-matched controls. Reconstructions of degenerative networks were performed using T1 magnetic resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron emission tomography (PET). Tract-specific fractional anisotropy (FA) quantification of 11 association fibers was performed while the clinical significance of the reconstructed structural or functional networks was determined by correlating them with the cognitive parameters. Compared with the controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were further stratified into 3 groups based on the cognitive severities. The spatial extents within the frontal-insular-caudate GM as well as the prefrontal WM AD increment regions determined the cognitive severities among 3 groups. Meanwhile, the prefrontal WM FA values and PET signals also correlated significantly with the patient's Mini-Mental State Examination score. Frontal hypometabolic patterns in PET analysis, even after adjusted for GM volume, were highly coherent to the GM atrophic regions, suggesting structural basis of functional alterations. Among the calculated major association bundles, only the anterior thalamic radiation FA values correlated significantly with all chosen cognitive scores. Our findings suggest that fronto-insular-caudate areas represent target degenerative network in CO intoxication. The topography that occurred at a cognitive severity-specific level at the chronic phase suggested the clinical roles of frontal areas. Although changes in FA are also diffusely distributed, different regional changes in AD suggested unequal long-term compensatory capacities among WM bundles. As such, the affected WM regions showing irreversible changes may exert adverse impacts to the interconnected GM structures.",carbon monoxide;charcoal;adult;anterior cingulate;article;brain atrophy;brain degeneration;California verbal learning test;carbon monoxide intoxication;caudate nucleus;charcoal burning suicide;clinical article;Clinical Dementia Rating;cognition;cognitive defect;controlled study;diffusion tensor imaging;dorsolateral prefrontal cortex;episodic memory;female;fractional anisotropy;gray matter;human;image quality;male;Mini Mental State Examination;neuroimaging;nuclear magnetic resonance imaging;positron emission tomography;posterior cingulate;prefrontal cortex;priority journal;Rey Osterrieth complex figure test;Stroop test;suicide;Taiwan;thalamus;verbal memory;white matter,"Chen, N. C.;Huang, C. W.;Huang, S. H.;Chang, W. N.;Chang, Y. T.;Lui, C. C.;Lin, P. H.;Lee, C. C.;Chang, Y. H.;Chang, C. C.",2015,,,0,
4979,Cognitive severity-specific neuronal degenerative network in charcoal burning suicide-related carbon monoxide intoxication: a multimodality neuroimaging study in Taiwan,"While carbon monoxide (CO) intoxication often triggers multiple intraneuronal immune- or inflammatory-related cascades, it is not known whether the pathological processes within the affected regions evolve equally in the long term. To understand the neurodegenerative networks, we examined 49 patients with a clinical diagnosis of CO intoxication related to charcoal burning suicide at the chronic stage and compared them with 15 age- and sex-matched controls. Reconstructions of degenerative networks were performed using T1 magnetic resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron emission tomography (PET). Tract-specific fractional anisotropy (FA) quantification of 11 association fibers was performed while the clinical significance of the reconstructed structural or functional networks was determined by correlating them with the cognitive parameters. Compared with the controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were further stratified into 3 groups based on the cognitive severities. The spatial extents within the frontal-insular-caudate GM as well as the prefrontal WM AD increment regions determined the cognitive severities among 3 groups. Meanwhile, the prefrontal WM FA values and PET signals also correlated significantly with the patient's Mini-Mental State Examination score. Frontal hypometabolic patterns in PET analysis, even after adjusted for GM volume, were highly coherent to the GM atrophic regions, suggesting structural basis of functional alterations. Among the calculated major association bundles, only the anterior thalamic radiation FA values correlated significantly with all chosen cognitive scores. Our findings suggest that fronto-insular-caudate areas represent target degenerative network in CO intoxication. The topography that occurred at a cognitive severity-specific level at the chronic phase suggested the clinical roles of frontal areas. Although changes in FA are also diffusely distributed, different regional changes in AD suggested unequal long-term compensatory capacities among WM bundles. As such, the affected WM regions showing irreversible changes may exert adverse impacts to the interconnected GM structures.",Adult;Anisotropy;Brain/ pathology;Carbon Monoxide/ toxicity;Charcoal;Cognition Disorders/ chemically induced;Female;Frontotemporal Lobar Degeneration/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Positron-Emission Tomography;Prefrontal Cortex/pathology;Severity of Illness Index;Suicide;Taiwan;White Matter/pathology,"Chen, N. C.;Huang, C. W.;Huang, S. H.;Chang, W. N.;Chang, Y. T.;Lui, C. C.;Lin, P. H.;Lee, C. C.;Chang, Y. H.;Chang, C. C.",2015,May,10.1097/md.0000000000000783,0,
4980,Detection of gray matter damage using brain MRI and SPECT in carbon monoxide intoxication: a comparison study with neuropsychological correlation,"PURPOSE: While lesion patterns in white matter have been extensively reported in the literature on carbon monoxide (CO) intoxication, reports on the effects on gray matter damage are less common. The aim of this study was to investigate regional damage patterns focusing on gray matter using (99m)Tc ethyl cysteinate dimer (ECD) brain single photon emission computed tomography (SPECT) and brain magnetic resonance imaging (MRI) with clinical correlation. PATIENTS AND METHODS: Thirty CO intoxication patients and 15 age-matched controls were enrolled for standard neuropsychological tests. Six regions of interest (ROI) were analyzed qualitatively and quantitatively in both SPECT and MRI. The patients were further grouped according to clinical dementia rating score. The sensitivity, specificity, and positive and negative predictive ratios related to dementia from both imaging modalities were further examined. RESULTS: In SPECT qualitative analysis, basal ganglia (n = 16) were the most common regions showing lower perfusion patterns. The basal ganglion and temporal, frontal, and parietal regions of the patients with dementia showed significantly lower perfusion patterns. MRI had a higher sensitivity while SPECT had a higher specificity and positive and negative predictive ratios in correlation with dementia among the ROI. The perfusion indices of the frontal, temporal, basal ganglion, and thalamus were inversely correlated with clinical severity (all P < 0.05). CONCLUSIONS: Our findings suggest that a multiparametric neuroimaging approach may provide more information in revealing the anatomical and neurobehavioral results in patients after CO intoxication. The atrophy pattern seen in MRI may explain in part the possible mechanism of the hypoperfusion state seen in SPECT.","Adult;Brain/ drug effects/pathology/physiopathology/ radionuclide imaging;Carbon Monoxide Poisoning/pathology/physiopathology/psychology/ radionuclide;imaging;Cerebrovascular Circulation/drug effects;Cognition/drug effects;Cysteine/analogs & derivatives;Dementia/complications;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Organotechnetium Compounds;Predictive Value of Tests;Tomography, Emission-Computed, Single-Photon","Chen, N. C.;Chang, W. N.;Lui, C. C.;Huang, S. H.;Lee, C. C.;Huang, C. W.;Chuang, Y. C.;Chang, C. C.",2013,Feb,10.1097/RLU.0b013e31827082a7,0,
4981,Atrial fibrillation and cognitive decline-the role of subclinical cerebral infarcts: The atherosclerosis risk in communities study,"BACKGROUND AND PURPOSE-: The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans. METHODS-: We analyzed data from 935 stroke-free participants (mean age±SD, 61.5±4.3 years; 62% women; and 51% black) from 1993 to 1995 through 2004 to 2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based prospective cohort study. Cognitive testing (including the digit symbol substitution and the word fluency tests) was performed in 1993 to 1995, 1996 to 1998, and 2004 to 2006 and brain MRI scans in 1993 to 1995 and 2004 to 2006. RESULTS-: During follow-up, there were 48 incident AF events. Incident AF was associated with greater annual average rate of decline in digit symbol substitution (-0.77; 95% confidence interval,-1.55 to 0.01; P=0.054) and word fluency (-0.80; 95% confidence interval,-1.60 to-0.01; P=0.048). Among participants without SCIs on brain MRI scans, incident AF was not associated with cognitive decline. In contrast, incident AF was associated with greater annual average rate of decline in word fluency (-2.65; 95% confidence interval,-4.26 to-1.03; P=0.002) among participants with prevalent SCIs in 1993 to 1995. Among participants who developed SCIs during follow-up, incident AF was associated with a greater annual average rate of decline in digit symbol substitution (-1.51; 95% confidence interval,-3.02 to-0.01; P=0.049). CONCLUSIONS-: The association of incident AF with cognitive decline in stroke-free individuals can be explained by the presence or development of SCIs, raising the possibility of anticoagulation as a strategy to prevent cognitive decline in AF. © 2014 American Heart Association, Inc.",anticoagulant agent;adult;article;brain infarction;brain ischemia;cardiovascular risk;cohort analysis;confidence interval;electrocardiogram;female;follow up;atrial fibrillation;human;major clinical study;male;mental deterioration;middle aged;multiracial person;nuclear magnetic resonance imaging;priority journal;prospective study,"Chen, L. Y.;Lopez, F. L.;Gottesman, R. F.;Huxley, R. R.;Agarwal, S. K.;Loehr, L.;Mosley, T.;Alonso, A.",2014,,,0,
4982,Improved power for characterizing longitudinal amyloid-beta PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region,"In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-beta (Abeta) PET changes and evaluating Abeta-modifying treatments. METHODS: Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Abeta-modifying treatments in Abeta-positive (Abeta+) and Abeta-negative (Abeta-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up ( approximately 24 mo) florbetapir PET scans from 332 Abeta+ and Abeta- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Abeta increases in Abeta+ and Abeta- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Abeta accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Abeta increases to clinical declines. RESULTS: As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Abeta increases and evaluate Abeta-modifying treatment effects in Abeta+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Abeta increases and clinical declines. CONCLUSION: A cerebral white matter reference region may improve the power to track longitudinal fibrillar Abeta increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Abeta-modifying treatments in randomized clinical trials.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/radionuclide imaging;Amyloid beta-Peptides/*chemistry;*Aniline Compounds;Apolipoprotein E4/genetics;Brain/pathology/radionuclide imaging;Brain Mapping/methods;Cerebellum/radionuclide imaging;Cerebrum/radionuclide imaging;Cognition Disorders/diagnosis/radionuclide imaging;*Ethylene Glycols;Female;Humans;Image Processing, Computer-Assisted/*methods;Longitudinal Studies;Male;Middle Aged;Pons/radionuclide imaging;Positron-Emission Tomography/*methods;Randomized Controlled Trials as Topic;Reference Values;Sample Size;Time Factors;White Matter/*radionuclide imaging;Alzheimer disease;biomarkers;clinical trial sample size;florbetapir PET;image analysis;statistical power","Chen, K.;Roontiva, A.;Thiyyagura, P.;Lee, W.;Liu, X.;Ayutyanont, N.;Protas, H.;Luo, J. L.;Bauer, R.;Reschke, C.;Bandy, D.;Koeppe, R. A.;Fleisher, A. S.;Caselli, R. J.;Landau, S.;Jagust, W. J.;Weiner, M. W.;Reiman, E. M.",2015,Apr,10.2967/jnumed.114.149732,0,
4983,Improved power for characterizing longitudinal amyloid-βPET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region,"In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Methods: Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. Results: As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. Conclusion: A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβincreases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.",,"Chen, K.;Roontiva, A.;Thiyyagura, P.;Lee, W.;Liu, X.;Ayutyanont, N.;Protas, H.;Luo Ji, L.;Bauer, R.;Reschke, C.;Bandy, D.;Koeppe, R. A.;Fleisher, A. S.;Caselli, R. J.;Landau, S.;Jagust, W. J.;Weiner, M. W.;Reiman, E. M.",2015,1,,0,
4984,Anton-Babinski syndrome in an old patient: A case report and literature review,"Anton-Babinski syndrome is a rare disease featuring bilateral cortical blindness and anosognosia with visual confabulation, but without dementia or any memory impairment. It has a unique neuropsychiatric presentation and should be highly suspected in those with odd visual loss and imaging evidence of occipital lobe injury. In the case discussed herein, a 90-year-old man presented with bilateral blindness, obvious anosognosia, and vivid visual confabulation, which he had had for 3 days. Brain computed tomography demonstrated recent hypodense infarctions at the bilateral occipital lobes. Thus, the patient was diagnosed with Anton-Babinski syndrome. Because of his age and the thrombolytic therapy during the golden 3hours after ischemic stroke, the patient received aspirin therapy rather than tissue plasminogen activator or warfarin. He gradually realized he was blind during the following week, but died of pneumonia 1month later. In the literature, it is difficult to establish awareness of blindness in patients with Anton-Babinski syndrome, but optimistically, in one report, a patient was aware of blindness within 2 weeks, without vision improvement. Our case illustrates that elderly patients with Anton-Babinski syndrome can partially recover and that 1week is the shortest time for the establishment of awareness of blindness for sufferers without vision improvement.",,"Chen, J. J.;Chang, H. F.;Hsu, Y. C.;Chen, D. L.",2015,1,,0,
4985,Ambient air pollution and neurotoxicity on brain structure: Evidence from women's health initiative memory study,"Objective: The aim of this study was to examine the putative adverse effects of ambient fine particulate matter (PM(2.5): PM with aerodynamic diameters <2.5μm) on brain volumes in older women. Methods: We conducted a prospective study of 1,403 community-dwelling older women without dementia enrolled in the Women's Health Initiative Memory Study, 1996-1998. Structural brain magnetic resonance imaging scans were performed at the age of 71-89 years in 2005-2006 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM(2.5) exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM(2.5) and brain volumes, adjusting for intracranial volumes and potential confounders. Results: Older women with greater PM(2.5) exposures had significantly smaller WM, but not GM, volumes, independent of geographical region, demographics, socioeconomic status, lifestyles, and clinical characteristics, including cardiovascular risk factors. For each interquartile increment (3.49μg/m(3)) of cumulative PM(2.5) exposure, the average WM volume (WMV; 95% confidence interval) was 6.23cm(3) (3.72-8.74) smaller in the total brain and 4.47cm(3) (2.27-6.67) lower in the association areas, equivalent to 1 to 2 years of brain aging. The adverse PM(2.5) effects on smaller WMVs were present in frontal and temporal lobes and corpus callosum (all p values <0.01). Hippocampal volumes did not differ by PM(2.5) exposure. Interpretation: PM(2.5) exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies.",,"Chen, J. C.;Wang, X.;Wellenius, G. A.;Serre, M. L.;Driscoll, I.;Casanova, R.;McArdle, J. J.;Manson, J. E.;Chui, H. C.;Espeland, M. A.",2015,1,,0,
4986,The NeuroAiD II (MLC901) in vascular cognitive impairment study (NEURITES) for the NEURITE investigators,"Background: A substantial proportion of patients after nondisabling stroke are cognitively impaired compared to age- and education-matched community-dwelling controls. Moreover, poststroke patients who have 'vascular cognitive impairment no dementia' (VCIND) of moderate severity have a high risk of incident dementia, dependency and death. Further studies are urgently needed to demonstrate effective cognition-enhancing therapies in VCIND given the scarcity of evidence-based treatment options. NeuroAiD is a traditional Chinese medicine that has been shown to induce neuroplasticity, promote cell proliferation and stimulate the development of dense axonal and dendritic networks in animal stroke models. NeuroAiD may improve cerebral blood flow and functional recovery after stroke in patients. Objective: To investigate the effects and tolerability of NeuroAiD",,"Chen, C. L. H.;Ikram, K.;Anqi, Q.;Yin, W. T.;Chen, A.;Venketasubramanian, N.",2013,March,,0,
4987,The NeuroAiD II (MLC901) in vascular cognitive impairment study (NEURITES),"BACKGROUND: A substantial proportion of patients after nondisabling stroke are cognitively impaired compared to age- and education-matched community-dwelling controls. Moreover, poststroke patients who have 'vascular cognitive impairment no dementia' (VCIND) of moderate severity have a high risk of incident dementia, dependency and death. Further studies are urgently needed to demonstrate effective cognition-enhancing therapies in VCIND given the scarcity of evidence-based treatment options. NeuroAiD is a traditional Chinese medicine that has been shown to induce neuroplasticity, promote cell proliferation and stimulate the development of dense axonal and dendritic networks in animal stroke models. NeuroAiD may improve cerebral blood flow and functional recovery after stroke in patients. OBJECTIVE: To investigate the effects and tolerability of NeuroAiD II in patients with VCIND. METHODS: The NeuroAiD II (MLC901) in Vascular Cognitive Impairment Study (NEURITES) is a 24-week, double-blind, randomized, placebo-controlled phase II study of NeuroAiD II in patients with VCIND. The primary outcome is executive function as measured by the Verbal Fluency test. Secondary outcomes include cognitive assessments such as the ADAS-Cog, MoCA, MMSE and Cognitive Battery: activities of daily living as measured by the Alzhei-mer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale for mild cognitive impairment, behavior as measured by the Neuropsychiatric Inventory, and depression as measured by the Geriatric Depression Scale and the Beck Depression Scale. In addition, there will be novel exploratory outcomes: (a) magnetic resonance imaging of lesion location (structural imaging), structural integrity of white matter pathways (diffusion tensor imaging), neuronal function (resting studies) and perfusion (arterial spin labeling and MR angiography), and (b) retinal and optic nerve imaging. Safety and tolerability will be assessed using adverse events, laboratory tests and vital signs. CONCLUSIONS: NEURITES has the potential to set new standards for the systematic evaluation of Asian traditional medicine for integration into standard medicine practice and establishing a novel therapeutic approach for improving cognition after stroke.","Activities of Daily Living;Aged;Aged, 80 and over;Biomarkers;Cerebral Angiography;Cerebrovascular Disorders/ complications/ drug therapy/psychology;Cognition Disorders/ drug therapy/ etiology/psychology;Depression/etiology/psychology;Double-Blind Method;Drugs, Chinese Herbal/adverse effects/ therapeutic use;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuroprotective Agents/adverse effects/ therapeutic use;Neuropsychological Tests;Randomized Controlled Trials as Topic;Retina/pathology;Sample Size;Stroke/ complications/ drug therapy/pathology/psychology;Treatment Outcome","Chen, C. L.;Ikram, K.;Anqi, Q.;Yin, W. T.;Chen, A.;Venketasubramanian, N.",2013,,10.1159/000346234,0,
4988,"Auditory P300, CT scans and cognitive state in Binswanger's disease","The P300 component of evoked potential can reflect cognitive state in dementia patients. The purpose of this study was to investigate the value of P300 as an indicator of cognition in Binswanger's disease (BD) and to explore the possible causes of dementia in BD patients. P300 was measured at Cz site in 21 patients with BD and 21 controls matched with age, sex, handedness, and education. This measurement included P300 latency and amplitude. All patients were also given WAIS-RC test and scanned with computerized tomography (CT), and were treated with hyperbaric oxygenation (HBO). The relationships among P300, CT and WAIS-RC score were studied. BD patients had significantly prolonged P300 latency and a tendency of low amplitude P300, but the amplitude difference was not significant compared with controls. P300 latency was found to be negatively correlated with WARS-RC scale, and positively correlated with the change of white matter low attenuation (WMLA). WMLA was also correlated with WAIS-RC score. Treatment with HBO reduced P300 latency and had effect on the cognitive part of P300 but had no effect on CT changes. The significant association between neurophysiological and neuropsychological measurement suggests that P300 measurement reflects a disrupted aspect of cognitive function in BD patients, and it may be a useful means to assess the degree of subcortical cognitive deterioration and the effect of therapy. White matter lesion in BD is concerned to the occurrence of dementia by disturbing axonal conduction.","Aged;Brain/*radiography;Cognition/*physiology;Dementia, Vascular/*physiopathology;Event-Related Potentials, P300/*physiology;Evoked Potentials, Auditory/*physiology;Female;Humans;Male;Middle Aged;Tomography, X-Ray Computed","Chen, C. F.;Jia, H. Y.;Zhao, X. Y.;Guo, H.;Luo, W.;Cao, X.",1997,,,0,
4989,Changes in anatomical and functional connectivity of Parkinson's disease patients according to cognitive status,"PURPOSE: This study assesses the patterns of structural and functional connectivity damage in patients with Parkinson's disease dementia (PDD) compared with cognitively unimpaired Parkinson's disease patients (PD-Cu) and healthy controls (HC). MATERIALS AND METHODS: Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor magnetic resonance imaging (DTI) scans were obtained from 30 PD and 21 sex- and age-matched HC. The between-group difference in posterior cingulate (PCC) functional connectivity (FC) was performed to assess FC dysfunction. Atlas-based spatial statistics of DTI was applied to compare White matter (WM) fibers impairment between groups. RESULTS: (1) Functional connectivity: (1) PD-Cu compared with HC showed a decreased PCC functional connectivity of the right medial temporal lobe (MTL). In addition, PCC-right MTL connectivity strength of PD was significantly correlated with Montreal Cognitive Assessment (MoCA) score. (2) PDD group shows a decreased FC of PCC-right parahippocampa compared with PD-Cu group; while show a widespread decreased PCC FC compared with HC group. (2) Anatomical connectivity: (1) Relative to PD-Cu, significant lower FA values were found in the left hippocampus in PDD. (2) PDD showed higher MD values in a widespread WM regions compared with PD-Cu and HC. (3) Positive correlation was observed between MoCA score and FA value of left inferior longitudinal and hippocampus, and bilateral superior longitudinal fasciculus in PD. CONCLUSIONS: Cognitive decline in PD is associated with FC damage of PCC-right MTL and microstructural damage of left hippocampus. Nevertheless, combining fMRI and DTI method may provide markers able to contribute to the prediction of PDD.",Cognition Disorders/ complications/physiopathology;Diffusion Magnetic Resonance Imaging;Female;Gyrus Cinguli/pathology;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Net/physiopathology;Parkinson Disease/ complications/physiopathology;White Matter/anatomy & histology/ pathology/ physiopathology,"Chen, B.;Fan, G. G.;Liu, H.;Wang, S.",2015,Jul,10.1016/j.ejrad.2015.04.014,0,
4990,"Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia","White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia.",,"Chen, A.;Akinyemi, R. O.;Hase, Y.;Firbank, M. J.;Ndung'u, M. N.;Foster, V.;Craggs, L. J.;Washida, K.;Okamoto, Y.;Thomas, A. J.;Polvikoski, T. M.;Allan, L. M.;Oakley, A. E.;O'Brien, J. T.;Horsburgh, K.;Ihara, M.;Kalaria, R. N.",2016,Jan,10.1093/brain/awv328,0,
4991,Functional magnetic resonance imaging responses in CADASIL,"Objectives The magnitude of the blood oxygen dependent level (BOLD) functional MRI (fMRI) response to visual stimulation is reduced in the small vessel disease cerebral amyloid angiopathy (CAA), reflecting impaired vascular reactivity. We determined whether BOLD responses were reduced in another small vessel disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods BOLD fMRI data were collected using a visual stimulus (contrast-reversing checkerboard) and motor task (finger-tapping). The amplitude of BOLD responses in the visual cortex (visual stimulus) and motor cortex (motor task) were compared between 5 CADASIL, 18 CAA and 18 control subjects, controlling for age and hypertension. Results BOLD response varied by group for the visual stimulus (p < 0.001) but not the motor task (p = 0.47). After adjusting for age and hypertension, the estimated mean visual cortex BOLD amplitude response was 3.95% in CADASIL (95% confidence interval, CI 3.15–4.75%), 1.73% in CAA (95% CI 1.19–2.27%), and 2.88% (95% CI 2.39–3.37%) in controls. In CADASIL, the visual BOLD response was greater than in CAA (p < 0.001) and controls (p = 0.04). Conclusions We observed increased and unchanged BOLD amplitude responses in the visual and motor cortices of CADASIL patients, respectively. This suggests that cortical blood flow regulation by neuronal activity may be relatively preserved in CADASIL, in contrast to CAA where occipital vascular reactivity is impaired. Cortical vascular reactivity in CADASIL may be preserved because the disease-related injury is primarily subcortical, whereas increased activation may reflect compensatory mechanisms for subcortical injury.",adult;aged;amplitude modulation;article;BOLD signal;brain blood vessel;brain hemorrhage;brain region;CADASIL;clinical article;confidence interval;controlled study;female;finger tapping test;functional magnetic resonance imaging;functional neuroimaging;human;hypertension;male;middle aged;mild cognitive impairment;motor cortex;motor performance;occipital lobe;priority journal;striate cortex;task performance;vascular amyloidosis;visual evoked potential;visual stimulation,"Cheema, I.;Switzer, A. R.;McCreary, C. R.;Hill, M. D.;Frayne, R.;Goodyear, B. G.;Smith, E. E.",2017,,10.1016/j.jns.2017.02.004,0,
4992,Cognitive function and brain structure correlations in healthy elderly East Asians,"We investigated the effect of age and health variables known to modulate cognitive aging on several measures of cognitive performance and brain volume in a cohort of healthy, non-demented persons of Chinese descent aged between 55 and 86 years. 248 subjects contributed combined neuropsychological, MR imaging, health and socio-demographic information. Speed of processing showed the largest age-related decline. Education and plasma homocysteine levels modulated age-related decline in cognitive performance. Total cerebral volume declined at an annual rate of 0.4%/yr. Gray and white matter volume loss was comparable in magnitude. Regionally, there was relatively greater volume loss in the lateral prefrontal cortex bilaterally, around the primary visual cortex as well as bilateral superior parietal cortices. Speed of processing showed significant positive correlation with gray matter volume in several frontal, parietal and midline occipital regions bilaterally. In spite of differences in diet, lifestyle and culture, these findings are broadly comparable to studies conducted in Caucasian populations and suggest generalizability of processes involved in age-related decline in cognition and brain volume.","Aged;Aged, 80 and over;Aging/ pathology/ physiology;Asian Continental Ancestry Group;Brain/ pathology/ physiology;Brain Mapping;Cognition/ physiology;Female;Humans;Image Interpretation, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Chee, M. W.;Chen, K. H.;Zheng, H.;Chan, K. P.;Isaac, V.;Sim, S. K.;Chuah, L. Y.;Schuchinsky, M.;Fischl, B.;Ng, T. P.",2009,May 15,10.1016/j.neuroimage.2009.01.036,0,
4993,Diagnosing CADASIL using MRI: evidence from families with known mutations of Notch 3 gene,"Clinical data and MRI findings are presented on 18 subjects from two families with neuropathologically confirmed CADASIL. DNA analysis revealed mutations in exon 4 of Notch 3 gene in both families. All family members with mutations in Notch 3 gene had extensive abnormalities on MRI, principally lesions in the white matter of the frontal lobes and in the external capsules. Of several family members in whom a diagnosis of CADASIL was suspected on the basis of minor symptoms, one had MRI changes consistent with CADASIL; none of these cases carried a mutation in the Notch 3 gene. MRI and clinical features that may alert the radiologist to the diagnosis of CADASIL are reviewed. However, a wide differential diagnosis exists for the MRI appearances of CADASIL, including multiple sclerosis and small-vessel disease secondary to hypertension. The definitive diagnosis cannot be made on MRI alone and requires additional evidence, where available, from a positive family history and by screening DNA for mutations of Notch 3 gene.","Adult;Aged;Cerebral Cortex/*pathology;Dementia, Multi-Infarct/*diagnosis/*genetics;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Mutation, Missense;Pedigree","Chawda, S. J.;De Lange, R. P.;Hourihan, M. D.;Halpin, S. F.;St Clair, D.",2000,Apr,,0,
4994,Reliability study of white matter rating scale for the dementia and disability in Thai Elderly Project,"OBJECTIVE: To study the reliability of white matter rating scale on magnetic resonance imaging (MRI) of elderly patients in the urban community of Bangkok. MATERIAL AND METHOD: One hundred elderly with clinical diagnosis of cognitive impairment in the urban community around Siriraj Hospital underwent cranial MRI according to the Dementia and Disability in Thai Elderly Project. The axial T1wi, T2wi, and fluid attenuated inversion recovery (FLAIR) were separately assessed by two neuroradiologists. The assessment included white matter change by using Scheltens' rating scale, atrophy, and evidence of infarction. The inter-rater agreements were analyzed. RESULTS: The inter-rater agreement of periventricular hyperintensities, white matter, basal ganglion and infratentorial foci of hyperintensities were very good (ICC = 0.89-0.98). The agreement was good for central atrophy (Kw = 0.66) and moderate for cortical atrophy (Kw = 0.49). The silent infarction was found in the study population and divided into cortical (15%), subcortical (26%), brainstem (3%), and infratentorial infarction (8%). CONCLUSION: White matter hyperintensities was an important radiological criteria for diagnosis of vascular dementia. Appropriate rating scale is necessary especially in research study. The authors found that Scheltens rating scale needed some training and slightly time consuming at the beginning but was a good reliable tool.","Aged;Asian Continental Ancestry Group;Atrophy/classification/pathology;Brain/ pathology;Cognition Disorders/pathology;Dementia/ pathology;Dementia, Vascular/ pathology;Diagnosis, Computer-Assisted;Disability Evaluation;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Observer Variation;Reproducibility of Results;Thailand;Urban Population","Chawalparit, O.;Wonglaksanapimon, S.;Songsaeng, D.;Saenanarong, V.",2009,Apr,,0,
4995,Clinical application of susceptibility weighted imaging: exploring from routine service,"To evaluate the usefulness of susceptibility weighted imaging (SWI) in clinical brain MRI. Retrospective study was performed after approval from institution Ethical Committee. The brain MRIs with SWI were selected from data base of the radiology department. Only cases with no abnormality in extra-axial location were included into the study. Two neuroradiologists revealed the images without knowledge of patients' history and diagnosis. The SWI was first interpreted. Then conventional MRI (cMRI) was interpreted after finishing data collection from SWI. Clinical data and final diagnosis were collected from information given on requested forms and followed up imaging studies. Descriptive analysis was performed. From January 2007 to December 2009, 82 cases were satisfied the inclusion criteria. There were 40 males and 42 females with age 7-79 years old (means = 47.45). The final diagnosis were normal brain imaging 4 cases (4.9%), dementia/atypical Parkinson disease 2 cases (2.4%), cerebrovascular disease 24 cases (29.3%), parenchymal brain tumors 35 cases (42.7%), infection 4 cases (4.9%), multiple sclerosis (MS) 6 cases (7.3%) and inconclusive diagnosis 7 cases (8.5%). The abnormalities found on SWI were related to cMRI in 67 cases (81.7%). Three cases (3.7%) had lesions on SWI not demonstrated on cMRI. The information got from SWI added on cMRI for interpretation and diagnosis in 43 cases (52.4%). SWI were shown more detectable microbleed and changing visualization of cortical and transmedullary veins. Microvascular structure inside the mass was demonstrated on SWI in brain tumor group. The increased transmedullary veins on SWI helped to confirm the non-neoplastic lesions. In selected cases with suspected or diagnosis of vascular disease and tumor, SWI added more information on cMRI especially microbleed and microvascular structure.",,"Chawalparit, O.;Tritrakarn, S. O.;Charnchaowanish, P.;Pornpunyawut, P.;Chobaroom, S.",2011,Mar 29,,0,
4996,Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample,"The main objective of the present study was to evaluate the diagnostic value (clinical application) of brain measures and cognitive function. Alzheimer and multi-infarct patients (N = 30) and normal subjects over the age of 50 (N = 40) were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.","Age Factors;Aged;Aged, 80 and over;Aging/ physiology;Alzheimer Disease/diagnosis;Analysis of Variance;Brain/ radiography;Cognition/ physiology;Dementia/ diagnosis/radiography;Dementia, Vascular/diagnosis;Educational Status;Female;Health Status;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Sensitivity and Specificity;Social Class","Chaves, M. L.;Ilha, D.;Maia, A. L.;Motta, E.;Lehmen, R.;Oliveira, L. M.",1999,Sep,,0,
4997,Association of Alzheimer's disease GWAS loci with MRI markers of brain aging,"Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta +/- SE = -0.047 +/- 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.","Aging/ genetics/ pathology;Alleles;Alzheimer Disease/ genetics/ pathology;Apolipoproteins E/genetics;Brain/ pathology;Female;Genome-Wide Association Study;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Organ Size/genetics;Polymorphism, Single Nucleotide;Risk;Sialic Acid Binding Ig-like Lectin 3/genetics","Chauhan, G.;Adams, H. H.;Bis, J. C.;Weinstein, G.;Yu, L.;Toglhofer, A. M.;Smith, A. V.;van der Lee, S. J.;Gottesman, R. F.;Thomson, R.;Wang, J.;Yang, Q.;Niessen, W. J.;Lopez, O. L.;Becker, J. T.;Phan, T. G.;Beare, R. J.;Arfanakis, K.;Fleischman, D.;Vernooij, M. W.;Mazoyer, B.;Schmidt, H.;Srikanth, V.;Knopman, D. S.;Jack, C. R., Jr.;Amouyel, P.;Hofman, A.;DeCarli, C.;Tzourio, C.;van Duijn, C. M.;Bennett, D. A.;Schmidt, R.;Longstreth, W. T., Jr.;Mosley, T. H.;Fornage, M.;Launer, L. J.;Seshadri, S.;Ikram, M. A.;Debette, S.",2015,Apr,10.1016/j.neurobiolaging.2014.12.028,0,
4998,Hemodynamic effects of cholinesterase inhibition in mild Alzheimer's disease,"PURPOSE: To evaluate the spatiotemporal progression of perfusion changes in early stages of Alzheimer's disease (AD), we imaged the perfusion response to pharmacological treatment in a group of mild AD patients and contrasted it to the perfusion of age-, sex-, and education-matched healthy volunteers over the same time interval. MATERIALS AND METHODS: We used pseudo continuous arterial spin labeling (PCASL) MRI for quantitative three-dimensional mapping of perfusion immediately before and 6 months after cholinesterase inhibitor treatment. RESULTS: Before treatment, patients were found hypoperfused relative to their healthy counterparts in the gray matter of lateral temporal lobe, posterior cingulate, and anterior cingulate as well as in the white matter of the posterior cingulate. Most of the cortical regions investigated and the white matter of posterior cingulate and prefrontal regions showed treatment-elicited increases in perfusion, which were not secondary to changes in regional tissue volume nor were they associated with improvement in either MMSE or ADAS-Cog scores, although lack of deterioration suggested a cognitive benefit. CONCLUSION: This study provides a hemodynamic profile of mild AD and sheds light on the perfusion changes related to prolonged cholinesterase inhibition in this early disease stage.",Aged;Alzheimer Disease/diagnosis/ drug therapy/ physiopathology;Blood Flow Velocity/drug effects;Brain/drug effects/physiopathology;Cerebrovascular Circulation/ drug effects;Cerebrovascular Disorders/diagnosis/ drug therapy/ physiopathology;Cholinesterase Inhibitors/ therapeutic use;Humans;Magnetic Resonance Angiography/ methods;Middle Aged;Treatment Outcome,"Chaudhary, S.;Scouten, A.;Schwindt, G.;Janik, R.;Lee, W.;Sled, J. G.;Black, S. E.;Stefanovic, B.",2013,Jul,10.1002/jmri.23967,0,
4999,Clinico-radiological predictors of vascular cognitive impairment (VCI) in patients with stroke: a prospective observational study,"BACKGROUND AND PURPOSE: Cognitive dysfunction occurs commonly following stroke and varies in severity. This study was aimed to determine the clinical, neuro-imaging, laboratory predictors of post stroke cognitive impairment and factors related to poor functional outcome in patients with post-stroke vascular cognitive impairment (VCI). MATERIAL AND METHODS: We prospectively evaluated 102 of 240 consecutive stroke patients for 6 months after incident stroke for development of VCI. Patients with VCI comprised of those with VCI-no dementia (VCIND) and vascular dementia (VaD). Functional outcome was assessed by modified Barthel index (MBI). RESULTS: Frequency of post-stroke VCI was 45.1% (46/102): 26.5% (27/102) having VCI-ND and 18.6% (19/102) having VaD. Patients with VCI were more likely to have lower educational and socioeconomic status, diabetes, hypertension, prior stroke, multiple risk factors, urinary incontinence, gait abnormality, peripheral signs of atherosclerosis, higher blood sugar level on admission and LDL levels, strategic site lesion, higher ARWMC (age related white matter changes) score, worse stroke severity (NIHSS) and functional outcome scores. On logistic regression analysis, lower educational status, strategic site lesion, higher ARWMC score and baseline stroke severity score were found to independently predict the risk of developing VCI. Worse stroke severity (NIHSS) scores and functional status scores at baseline predicted poor outcome in patients with VCI. CONCLUSION: Post-stroke cognitive impairment is frequent and is associated with poor functional outcome. Predictors like lower educational status, strategic site lesion, greater severity of age related white matter changes and baseline stroke severity independently contributed to the risk of developing VCI in stroke patients.","Aged;Blood Glucose;Cholesterol, LDL/blood;Cognition Disorders/ diagnosis/ etiology;Dementia, Vascular/ diagnosis/ etiology;Female;Humans;Male;Middle Aged;Multivariate Analysis;Neuroimaging;Neuropsychological Tests;Observation;Predictive Value of Tests;Prospective Studies;Risk Factors;Severity of Illness Index;Stroke/ complications","Chaudhari, T. S.;Verma, R.;Garg, R. K.;Singh, M. K.;Malhotra, H. S.;Sharma, P. K.",2014,May 15,10.1016/j.jns.2014.03.018,0,
5000,Verbal working and long-term episodic memory associations with white matter microstructure in normal aging investigated using tract-based spatial statistics,"Reductions in the integrity of white matter microstructure are thought to be a significant cause of age-related decline in mnemonic abilities, including working memory (WM) and long-term episodic memory (LTM). This study uses tract-based spatial statistics (TBSS) applied to diffusion tensor magnetic resonance images to explore correlations between white matter microstructure and verbal WM and LTM in a sample of 98 normal older adults. WM performance was associated with microstructure in left fronto-parietal pathways and LTM was associated with bilateral fronto-temporal pathways. Interhemispheric-frontal pathways (genu of the corpus callosum) were associated with both types of mnemonic function. We hypothesize that in normal aging, damage to certain white matter pathways may reduce the dynamic efficiency of mnemonic abilities by disrupting the connections within multiple distributed networks. By correlating white matter with two mnemonic functions in the same analysis, we have demonstrated that regional white matter networks may share common mnemonic functions but also may be differentiated for memory types. © 2013 American Psychological Association.",,"Charlton, R. A.;Barrick, T. R.;Markus, H. S.;Morris, R. G.",2013,Sep,,0,
5001,"CT and MRI findings among African-Americans with Alzheimer's disease, vascular dementia, and stroke without dementia","We compared CT and MRI findings among 78 Alzheimer's disease (AD), 66 vascular dementia (VaD), and 41 stroke without dementia (SWD) African- American patients to identify possible neuroimaging indicators of dementia. The patients with AD and VaD were generally older and less educated than those with SWD. VaD and SWD patients had a higher frequency of cardiovascular disease risk factors than those with AD. In multivariate analysis, the CT data showed that the presence of white matter lesions, nonlacunar infarcts, and left subcortical infarcts were predictors of VaD when compared with AD, whereas atrophy of the third ventricle and equal distribution of white matter lesions distinguished VaD from SWD. On MRI, atrophy of the temporal sulci, temporal horns, and the third ventricle, and right hemisphere infarcts, distinguished AD from VaD, while atrophy of the third ventricle differentiated VaD from SWD. These data suggest that atrophy, especially at the level of the third ventricle, presence of infarcts, and white matter lesions may be useful predictors of dementia subtype. Furthermore, the qualitative CT and MRI findings among our African-American patients were similar to those reported in other dementia studies.",aged;Alzheimer disease;article;brain atrophy;brain infarction;cardiovascular disease;computer assisted tomography;dementia;diagnostic imaging;female;human;major clinical study;male;multiinfarct dementia;Black person;nuclear magnetic resonance imaging;priority journal;risk factor;cerebrovascular accident;white matter,"Charletta, D.;Gorelick, P. B.;Dollear, T. J.;Freels, S.;Harris, Y.",1995,,,0,
5002,Exploring cerebral small vessel disease research using informetrics: A first glimpse into microbleeds,,Alzheimer disease;brain hemorrhage;cerebrovascular disease;cognitive defect;human;letter;nuclear magnetic resonance imaging;priority journal;vascular amyloidosis,"Charidimou, A.;Yeon, S.;Song, M.",2015,,,0,
5003,Cerebral microbleeds and cognition in cerebrovascular disease: An update,"Sporadic cerebral small vessel disease is a major cause of cognitive impairment. MRI is an important tool for detecting and mapping cerebral small vessel disease in vivo. Lacunes and white matter changes are recognized as characteristic MRI manifestations of small vessel disease. Cerebral microbleeds (CMBs) - small, perivascular haemorrhages seen as well-demarcated, hypointense, rounded lesions on MRI sequences sensitive to magnetic susceptibility - are a more recently recognized MRI marker of small vessel pathology. CMBs are increasingly found in various patient populations and disease settings, including first-ever and recurrent ischaemic or haemorrhagic stroke, Alzheimer's disease, vascular cognitive impairment and healthy elderly individuals. Increasing evidence suggests that the anatomical distribution of CMBs (lobar or deep) may have diagnostic value in detecting small vessel disease subtypes including hypertensive arteriopathy and cerebral amyloid angiopathy. However, the relevance of CMBs for cognitive impairment remains uncertain. The study of CMBs and cognition in populations with cerebrovascular disease presents a special challenge as they coexist and correlate with other cerebrovascular pathologies. This review updates current thinking on how CMBs may be relevant in the study of cognitive impairment in populations with cerebrovascular disease, and how they can contribute in understanding the links between cerebrovascular and degenerative pathologies. © 2012 Elsevier B.V.",Alzheimer disease;artery disease;article;brain hemorrhage;brain region;CADASIL;cerebrovascular accident;cerebrovascular disease;cognition;cognitive defect;disease association;disease severity;executive function;histopathology;human;nuclear magnetic resonance imaging;priority journal;prognosis;vascular amyloidosis,"Charidimou, A.;Werring, D. J.",2012,,,0,
5004,"Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1)","Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, ""high risk"" elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (>/=3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58-2.89 and adj-HR: 2.09; 95% CI: 1.71-2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68-8.08 and adj-HR: 3.93; 95% CI: 2.71-5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24-1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00-1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.",Antithrombotic;brain microbleeds;cerebral microbleeds;cerebral small vessel disease;intracerebral hemorrahage;magnetic resonance imaging,"Charidimou, A.;Shams, S.;Romero, J. R.;Ding, J.;Veltkamp, R.;Horstmann, S.;Eiriksdottir, G.;van Buchem, M. A.;Gudnason, V.;Himali, J. J.;Gurol, M. E.;Viswanathan, A.;Imaizumi, T.;Vernooij, M. W.;Seshadri, S.;Greenberg, S. M.;Benavente, O. R.;Launer, L. J.;Shoamanesh, A.;International, Meta-Microbleeds Initiative",2018,Jan 1,,0,
5005,The concept of sporadic cerebral small vessel disease: A road map on key definitions and current concepts,"Sporadic cerebral small vessel disease is considered to be among the most common known neuropathological processes and has an important role in stroke, cognitive impairment, and functional loss in elderly persons. The term is now commonly used to describe a range of neuroimaging, neuropathological, and associated clinical features, the pathogenesis of which is largely unclear but that are thought to arise from disease affecting the perforating cerebral arterioles, capillaries, and venules. Modern neuroimaging has revolutionized our understanding of the consequences of small vessels disease on the brain parenchyma, even though small arteries, arterioles, capillaries, and venules are difficult to be directly visualized with current techniques used in clinical practice. In this short review, we focus on histopathological and neuroimaging perspectives, basic definitions, and recent advances in the field.",amyloid beta protein;glial fibrillary acidic protein;article;blood vessel diameter;brain atrophy;brain hemorrhage;brain infarction;cerebrovascular disease;clinical feature;cortical superficial siderosis;disease association;disease marker;histopathology;human;hypertensive arteriopathy;image analysis;medical research;molecular imaging;neuroimaging;neuropathology;nuclear magnetic resonance imaging;pathophysiology;perivascular space;positron emission tomography;priority journal;radiation and radiation related phenomena;siderosis;small subcortical infarct;sporadic cerebral small vessel disease;standardization;vascular amyloidosis;white matter hyperintensity,"Charidimou, A.;Pantoni, L.;Love, S.",2016,,,0,
5006,Cortical Superficial Siderosis in Memory Clinic Patients: Further Evidence for Underlying Cerebral Amyloid Angiopathy,"BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with many cases of spontaneous symptomatic lobar intracerebral haemorrhage in older individuals and is emerging as an important contributor to cognitive impairment. Cortical superficial siderosis (cSS) is an increasingly recognized haemorrhagic neuroimaging manifestation of CAA. We sought to investigate its prevalence and its association with underlying CAA among memory clinic patients. METHODS: We included consecutive eligible patients who presented to the out-patient memory clinic at the Massachusetts General Hospital from 2007 to 2010 and had appropriate MRI, including blood-sensitive sequences. We analyzed the prevalence and topography of cSS according to demographic, clinical, APOE and MRI data. RESULTS: Our cohort consisted of 339 memory clinic patients: Alzheimer's disease (n = 86); mild cognitive impairment (n = 162); vascular dementia/mixed dementia (n = 18); other dementia/undetermined (n = 42); and subjective cognitive complains (n = 31). cSS was detected in 10 patients (3%; 95% CI 1.4-5.4): in 7 cases cSS was focal and in 3 cases, it was disseminated. In multivariable logistic regression analysis, the presence of cSS was associated with lobar microbleeds (OR 1.08; 95% CI 1.03-1.13; p = 0.001, per each additional microbleed) and severe white matter hyperintensities (Fazekas score 5-6, OR 4.43; 95% CI 1.21-26.28; p = 0.028) after adjusting for age. These associations were not influenced by the clinical diagnosis. In patients with APOE data, the APOE epsilon4/epsilon4 genotype was overrepresented among subjects with vs. without cSS. In the subgroup of patients with probable CAA (n = 68; 9 with cSS) based on the presence of strictly lobar microbleeds, cSS was also associated with a higher prevalence of severe white matter hyperintensities (66.7 vs. 10.2%; p = 0.001), high centrum semiovale perivascular spaces burden (88.9 vs. 52.4%; p = 0.041) and higher counts of lobar microbleeds (median 13; IQR 10-36 vs. median 1; IQR 1-2; p < 0.00001), compared to patients without cSS. CONCLUSIONS: Our data provide further evidence supporting the hypothesis that cSS is a manifestation of advanced CAA in memory clinic populations. Future longitudinal studies should explore any direct effect of cSS on cognition or haemorrhage risk and disease progression.",,"Charidimou, A.;Ni, J.;Martinez-Ramirez, S.;Vashkevich, A.;Ayres, A.;Rosand, J.;Gurol, E. M.;Greenberg, S. M.;Viswanathan, A.",2016,,10.1159/000442299,0,
5007,Cerebral microbleeds: A guide to detection and clinical relevance in different disease settings,"Cerebral microbleeds have emerged as an important new imaging marker of cerebral small vessel disease. With the development of MRI techniques that are exquisitely sensitive to paramagnetic blood products, such as T2-weighted gradient-recalled echo and susceptibility-weighted sequences, microbleeds have been detected in ever-increasing numbers of patients in stroke and cognitive clinics, as well as in healthy older people and in a variety of other rarer diseases and syndromes. Detection of cerebral microbleeds has clinical implications with respect to the diagnosis of the underlying small vessel disease, the safety of antithrombotic use, and the risk of symptomatic intracerebral haemorrhage, cognitive impairment and dementia. This article provides a guide to the detection and clinical relevance of cerebral microbleeds in different conditions based on a comprehensive review of the literature and own findings in research and clinical practice. © 2013 Springer-Verlag Berlin Heidelberg.",,"Charidimou, A.;Krishnan, A.;Werring, D. J.;Rolf Jäger, H.",2013,June,,0,
5008,The dark matter of cerebral microbleeds: Implications for thrombolysis and other clinical scenarios,,tissue plasminogen activator;aging;blood clot lysis;brain aging;brain hemorrhage;cerebrovascular accident;clinical outcome;clinical practice;dementia;disease association;disease predisposition;human;letter;meta analysis (topic);neuroimaging;nuclear magnetic resonance imaging;priority journal,"Charidimou, A.",2016,,10.1001/jamaneurol.2016.2948,0,
5009,Cerebral Amyloid Angiopathy-Related Inflammation Biomarkers: Where are we Now?,"Cerebral amyloid angiopathy- related inflammation (CAA-ri) is an aggressive disease subtype of CAA with characteristic clinical and radiological findings. CAA-ri is an important diagnosis to reach in clinical practice, as patients typically respond to prompt immunosuppressive treatment. A definitive diagnosis of CAA-ri still requires a brain biopsy, and hence developing non-invasive diagnostic criteria and biomarkers for this syndrome are key priorities in the field. CAA-ri has gained additional interest for its notable similarities to amyloid-related imaging abnormalities, a complication of immunotherapy treatments in Alzheimer's disease patients. In this commentary, the current state of biomarkers research for CAA-ri and recently suggested diagnostic criteria are put into context.",,"Charidimou, A.",2016,Jan 6,10.3233/jad-151042,0,
5010,Morphologic and neuropsychological patterns in patients suffering from Alzheimer's disease,"INTRODUCTION: We conducted a retrospective study to identify morphological subgroups of patients referred for AD or aMCI and to seek for differences across neuropsychological performances. METHODS: One hundred forty-five patients (mean age = 76.01, 88 women and 57 men) referred for AD, either at the stage of dementia or aMCI, were examined using structural MRI. Five observers reviewed blindly twice all examinations. We rated microangiopathy, hippocampal, parietal atrophies, including a gradient of fronto-parietal atrophy (GFPA). A multiple component analysis (MCA) followed by a hierarchical ascending classification was conducted to identify morphologically distinct subgroups. Among these, 76 patients completed all the neuropsychological tests. Univariate and multivariate analyses were further conducted on these data across morphological subgroups. The institutional review board approved the research protocol. RESULTS: Inter- and intra-raters' agreements were excellent and very good for microangiopathy and hippocampal atrophy ratings. They were higher for GFPA than for the parietal atrophy scale. MCA without priors identified three groups: group 1 was characterized by no/discrete microangiopathy, severe hippocampal, and predominant parietal atrophy; group 2 had significant microangiopathy, severe hippocampal atrophy, and no predominant parietal atrophy; group 3 had a mild hippocampal atrophy and parietal atrophies. In group 1, working memory profile was less impaired than in group 2 (p = 0.01). Neuropsychological performances of group 3 were higher in most domains. CONCLUSION: Combined characterization of microangiopathy, hippocampal, parietal, and GFPA allows identifying morphological subgroups among patients referred for AD and at risk. These groups have some neuropsychological differences, suggesting different pathophysiological mechanisms or co-existing conditions.",,"Chapuis, P.;Sauvee, M.;Medici, M.;Serra, A.;Banciu, E.;Moreau-Gaudry, A.;Moreaud, O.;Krainik, A.",2016,May,10.1007/s00234-016-1659-0,0,
5011,Patterns of white matter atrophy in frontotemporal lobar degeneration,"BACKGROUND: Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter (WM) alterations in this disease. OBJECTIVES: To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degeneration-frontotemporal dementia (FTD) and semantic dementia-and to compare the patterns of WM atrophy with those of gray matter (GM) atrophy in these diseases. DESIGN: Structural MRIs were obtained from patients with FTD (n = 12) and semantic dementia (n = 13) and in cognitively healthy age-matched controls (n = 24). Regional GM and WM were classified automatically from high-resolution T1-, T2-, and proton density-weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates. RESULTS: Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD. CONCLUSIONS: These results show that patients with frontotemporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders.","Aged;Atrophy;Brain Mapping;Cerebral Cortex/ pathology;Dementia/ pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuroglia/ pathology;Species Specificity","Chao, L. L.;Schuff, N.;Clevenger, E. M.;Mueller, S. G.;Rosen, H. J.;Gorno-Tempini, M. L.;Kramer, J. H.;Miller, B. L.;Weiner, M. W.",2007,Nov,10.1001/archneur.64.11.1619,0,
5012,"Associations between White Matter Hyperintensities and β Amyloid on Integrity of Projection, Association, and Limbic Fiber Tracts Measured with Diffusion Tensor MRI","The goal of this study was to assess the relationship between Aβ deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Aβ deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue. © 2013 Chao et al.",amyloid beta protein;apolipoprotein E4;Pittsburgh compound B;aged;arteriosclerosis;article;brain blood vessel;brain infarction size;brain region;brain size;capsula interna;cerebrovascular disease;Clinical Dementia Rating;corona radiata (brain);corpus callosum;diffusion tensor imaging;disease severity;female;fractional anisotropy;genotype;human;image analysis;image processing;limbic system;major clinical study;male;mild cognitive impairment;nerve projection;nerve tract;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;organ size;parahippocampal gyrus;positron emission tomography;protein interaction;protein localization;risk factor;white matter lesion;white matter volume;Magnetom Trio Syngo System,"Chao, L. L.;DeCarli, C.;Kriger, S.;Truran, D.;Zhang, Y.;Laxamana, J.;Villeneuve, S.;Jagust, W. J.;Sanossian, N.;Mack, W. J.;Chui, H. C.;Weiner, M. W.",2013,,,0,
5013,"Associations between white matter hyperintensities and beta amyloid on integrity of projection, association, and limbic fiber tracts measured with diffusion tensor MRI","The goal of this study was to assess the relationship between Abeta deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78+/-7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Abeta deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Abeta deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Abeta deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE epsilon4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue.","Aged;Aged, 80 and over;Amyloid beta-Peptides/ genetics/metabolism;Anisotropy;Apolipoprotein E4/ genetics/metabolism;Brain Mapping;Diffusion Tensor Imaging;Female;Gene Expression;Humans;Limbic System/metabolism/ pathology;Longitudinal Studies;Male;Mild Cognitive Impairment/diagnosis/ genetics/ pathology/physiopathology;Multivariate Analysis;Neuropsychological Tests","Chao, L. L.;Decarli, C.;Kriger, S.;Truran, D.;Zhang, Y.;Laxamana, J.;Villeneuve, S.;Jagust, W. J.;Sanossian, N.;Mack, W. J.;Chui, H. C.;Weiner, M. W.",2013,,10.1371/journal.pone.0065175,0,
5014,"Parvalbumin neurons in the hippocampus in senile dementia of the Alzheimer type, Parkinson's disease and multi-infarct dementia","The immunogold-silver-staining method (IGSS) was used for the detection of hippocampal neurons containing the cytoplasmic calcium-binding protein parvalbumin in senile dementia of the Alzheimer type (SDAT), Parkinson's disease and multi-infarct dementia (MID). Computer-based image analysis of cell numbers in the hippocampus proper and the entorhinal cortex, measurement of total dendritic length of selected neurons and quantitative microdensitometry of immunoreacted sections was performed. In severe SDAT cases a loss of parvalbumin immunoreactive (parv-i) neurons and a reduction of dendritic fields was detected especially in CA1 and the subiculum. In the entorhinal cortex the general atrophy exceeded the decrease of pamalbumin immunoreactivity. Mild SDAT cases showed only minor alterations of parv-i neurons and in cases of parkinsonism without cognitive disorders or in those with depression parv-i neurons were not affected. However, in cases of parkinsonism with dementia and in MID a severe cell loss and a drastic reduction of dendritic arborization in the hippocampus proper was detected, which was accompanied by additional morphological alterations due to ischemic damage. We conclude that parv-i neuronal networks in the hippocampus are damaged in some patients with dementing disorders in SDAT, Parkinson's disease and MID consecutive to Alzheimer or ischemia related pathology.",,"Chan-Palay, V.;Zetsche, T.;Hochli, M.",1991,1991,,0,
5015,Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease,"BACKGROUND: Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden. METHODS: Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr) in 8 cortical volumes-of- interests (VOIs). The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates. RESULTS: Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024), but not regional (r = 0.264, p = 0.223) AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004), superior medial- (r = 0.443, p = 0.034), and middle-prefrontal (r = 0.448, p = 0.032) regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019) and hippocampal volume (r = -0.469, p = 0.016) showed significant correlations while the prefrontal (r = -0.417, p = 0.043) or hippocampal volume (r = -0.422, p = 0.04) also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume. CONCLUSIONS: BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD.",,"Chang, Y. T.;Huang, C. W.;Chen, N. C.;Lin, K. J.;Huang, S. H.;Chang, Y. H.;Hsu, S. W.;Chang, W. N.;Lui, C. C.;Hsu, C. W.;Chang, C. C.",2016,,10.1371/journal.pone.0149056,0,
5016,Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease,"The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp 38:3039-3051, 2017. (c) 2017 The Authors Human Brain Mapping Published Wiley by Periodicals, Inc.",Alzheimer's disease;anatomical structural covariance;default-mode network;genetic effect;posterior cingulate cortex,"Chang, Y. T.;Hsu, S. W.;Tsai, S. J.;Chang, Y. T.;Huang, C. W.;Liu, M. E.;Chen, N. C.;Chang, W. N.;Hsu, J. L.;Lee, C. C.;Chang, C. C.",2017,Jun,,0,5017
5017,Genetic effect of MTHFR C677T polymorphism on the structural covariance network and white-matter integrity in Alzheimer's disease,"The 677 C to T transition in the MTHFR gene is a genetic determinant for hyperhomocysteinemia. We investigated whether this polymorphism modulates gray matter (GM) structural covariance networks independently of white-matter integrity in patients with Alzheimer's disease (AD). GM structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed-based analysis. The patients were divided into two genotype groups: C homozygotes (n = 73) and T carriers (n = 62). Using diffusion tensor imaging and white-matter parcellation, 11 fiber bundle integrities were compared between the two genotype groups. Cognitive test scores were the major outcome factors. The T carriers had higher homocysteine levels, lower posterior cingulate cortex GM volume, and more clusters in the dorsal medial lobe subsystem showing stronger covariance strength. Both posterior cingulate cortex seed and interconnected peak cluster volumes predicted cognitive test scores, especially in the T carriers. There were no between-group differences in fiber tract diffusion parameters. The MTHFR 677T polymorphism modulates posterior cingulate cortex-anchored structural covariance strength independently of white matter integrities. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.",Alzheimer's disease;anatomical structural covariance;default-mode network;genetic effect;posterior cingulate cortex,"Chang, Y. T.;Hsu, S. W.;Tsai, S. J.;Chang, Y. T.;Huang, C. W.;Liu, M. E.;Chen, N. C.;Chang, W. N.;Hsu, J. L.;Lee, C. C.;Chang, C. C.",2017,Mar 25,,0,
5018,Montreal cognitive assessment in assessing clinical severity and white matter hyperintensity in Alzheimer's disease with normal control comparison,"PURPOSE: Use Taiwanese version of the Montreal Cognitive Assessment (MoCA) in evaluating patients in different stages of Alzheimer's disease (AD) and correlate with white matter change. METHODS: Ninety-seven normal controls (NC), 52 very-mild AD (clinical dementia rating [CDR] = 0.5), 48 mild AD (CDR = 1) and 38 moderate AD (CDR = 2) patients were enrolled for the MoCA, Mini- Mental State Examination (MMSE) and the Cognitive Assessment Screening Instrument (CASI). White matter hyperintensities (WMHs) on brain MRI were visually rated and classified as deep or periventricular WMHs. RESULTS: In NC group, education (beta = 0.326) but not age (beta = -0.183, p = 0.069), was significantly related to MoCA score. However, while we added two points to the AD patients with less than 6 years education, the effects of education disappeared as compared with those of 7 years of education. For all educational levels, the cutoff value of MoCA for very-mild AD was 22/23 (sensitivity = 82.7%, specificity = 87.6%). No significant differences were found in the areas under the curves that differentiated NC from the patients with AD for MoCA and MMSE (differences = 0.008, p = 0.490), or for MoCA and CASI (differences = 0.023, p = 0.082). Total WMHs, frontal deep and periventricular WMHs were inversely correlated with the attention and delayed-recall subdomain. CONCLUSION: The MoCA is a good clinical tool for screening very-mild stage AD if the educational effects are carefully considered. The correlation between the executive subdomains with the frontal WMHs also makes it a useful tool for detecting subtle WMHs.","Aged;Aged, 80 and over;Alzheimer Disease/*complications/pathology;Brain/*pathology;Chi-Square Distribution;Cognition Disorders/*diagnosis/*etiology;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Nerve Fibers, Myelinated/*pathology;*Neuropsychological Tests;ROC Curve;Taiwan","Chang, Y. T.;Chang, C. C.;Lin, H. S.;Huang, C. W.;Chang, W. N.;Lui, C. C.;Lee, C. C.;Lin, Y. T.;Chen, C. H.;Chen, N. C.",2012,Jun,,0,
5019,Clinical Dementia Rating Scale Detects White Matter Changes in Older Adults at Risk for Alzheimer's Disease,"This study investigated the putative changes in regional gray matter and cingulum bundle segments in mild cognitive impairment (MCI) by using two diagnostic criteria. Participants comprised 50 older adults with MCI and 22 healthy older controls (HC). The older adults with MCI were further divided into two groups defined by a global Clinical Dementia Rating (CDR) score of 0.5 and with (the CDR/NPT MCI group) or without (the CDR MCI group) objective cognitive impairments determined using neuropsychological tests (NPTs). Comparable regional gray matter integrity was observed among the three groups. However, the integrity of the right inferior segment of the cingulum bundle in the two MCI groups was more reduced than that in the HC group, and the CDR/NPT MCI group exhibited additional disruption in the left inferior cingulum bundle. The results also demonstrated that neuropsychological measures have greater predictive value for changes in white matter beyond the contribution of an informant-based instrument alone. Overall, the findings confirm the utility of informant-based assessment in detecting microstructural brain changes in high-risk older adults, even before objective cognitive impairment is evident. The findings also suggest that combining the neuropsychological measures with the informant-based assessment provided the greatest predictive value in assessing white matter disruption. The essential role of the white matter measurement as a biomarker for detecting individuals at a high risk of developing dementia was highlighted.",,"Chang, Y. L.;Yen, Y. S.;Chen, T. F.;Yan, S. H.;Tseng, W. Y.",2015,Nov 30,10.3233/jad-150599,0,
5020,"Regional cingulum disruption, not gray matter atrophy, detects cognitive changes in amnestic mild cognitive impairment subtypes","Amnestic mild cognitive impairment (aMCI), which has a high risk of progression to Alzheimer's disease (AD), can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. We investigated the integrity of regional gray matter and segments of the cingulum bundle with diffusion spectrum imaging tract-specific analysis, and their relationships to neuropsychological functioning, in 46 individuals with aMCI (S-aMCI n = 24; M-aMCI n = 22) and 36 healthy controls (HC). Results demonstrated that although both aMCI groups were impaired on all memory measures relative to HCs, the M-aMCI group demonstrated worse performance on paired association memory and on selective executive function relative to the S-aMCI group. The two aMCI groups did not show significant atrophy in regional gray matter indices as compared to the HC group, but the M-aMCI group showed significant disruption in white matter of the left anterior and inferior cingulum bundles relative to the S-aMCI and HC groups. Furthermore, disruption in the inferior cingulum bundles was significantly associated with executive function and attention/processing speed in all aMCI participants above and beyond the contribution of bilateral hippocampal volumes. Overall, these results indicate that the degeneration of cingulum fibers did not appear to arise from degeneration of the corresponding cerebral cortex. It also suggests relatively greater sensitivity of a white matter biomarker and comprehensive neuropsychological evaluation over gray matter biomarkers in early detection of AD.","Aged;Analysis of Variance;Association Learning/physiology;Atrophy/pathology;Brain Mapping;Disease Progression;Executive Function;Female;Functional Laterality;Gray Matter/pathology;Gyrus Cinguli/ pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Memory;Mild Cognitive Impairment/ classification/ diagnosis;Neuropsychological Tests;White Matter/ pathology","Chang, Y. L.;Chen, T. F.;Shih, Y. C.;Chiu, M. J.;Yan, S. H.;Tseng, W. Y.",2015,,10.3233/jad-141839,0,
5021,The Effects of an APOE Promoter Polymorphism on Human White Matter Connectivity during Non-Demented Aging,"Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort. Network communication efficiency was quantified, along with the network's betweenness centrality (Bc), global efficiency, local efficiency, and shortest path length. Regarding cognition, TT carriers had significant negative correlations between age and memory performance and between age and executive functions. A network analysis showed that TT carriers had an accelerated age-related loss of Bc and that regional Bc decreased in the left inferior frontal gyrus pars opercularis, the left posterior cingulate cortex, the right inferior occipital gyrus (IOG.R), and the left angular gyrus (ANG.L). Additional brain-behavior relationship analyses showed that polymorphism of rs405509 and age have strong interaction effects on the association of nodal Bc and cognition, mainly in the IOG.R and ANG.L. These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.","0 (Apolipoproteins E);Aged;Aging/ genetics/pathology/psychology;Apolipoproteins E/ genetics;Brain/ diagnostic imaging;Connectome;Diffusion Magnetic Resonance Imaging;Executive Function;Female;Humans;Longitudinal Studies;Male;Memory;Middle Aged;Neural Pathways/diagnostic imaging;Polymorphism, Genetic;Promoter Regions, Genetic;White Matter/ diagnostic imaging;APOE promoter;brain connectome;cognitive aging;diffusion MRI;graph theory","Chang, P.;Li, X.;Ma, C.;Zhang, S.;Liu, Z.;Chen, K.;Ai, L.;Chang, J.;Zhang, Z.",2017,,,0,5022
5022,The Effects of an APOE Promoter Polymorphism on Human White Matter Connectivity during Non-Demented Aging,"Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort. Network communication efficiency was quantified, along with the network's betweenness centrality (Bc), global efficiency, local efficiency, and shortest path length. Regarding cognition, TT carriers had significant negative correlations between age and memory performance and between age and executive functions. A network analysis showed that TT carriers had an accelerated age-related loss of Bc and that regional Bc decreased in the left inferior frontal gyrus pars opercularis, the left posterior cingulate cortex, the right inferior occipital gyrus (IOG.R), and the left angular gyrus (ANG.L). Additional brain-behavior relationship analyses showed that polymorphism of rs405509 and age have strong interaction effects on the association of nodal Bc and cognition, mainly in the IOG.R and ANG.L. These results demonstrate that the rs405509 T/T allele of APOE causes an age-related cognitive decline in non-demented elderly people, possibly by modulating brain network communication efficiency, which may be beneficial for understanding the neural mechanisms of rs405509-related cognitive aging and AD pathogenesis.",APOE promoter;brain connectome;cognitive aging;diffusion MRI;graph theory,"Chang, P.;Li, X.;Ma, C.;Zhang, S.;Liu, Z.;Chen, K.;Ai, L.;Chang, J.;Zhang, Z.",2016,Sep 13,10.3233/jad-160447,0,
5023,"A cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy pedigree: clinical pathology, neuroimaging and molecular genetics studies","OBJECTIVE: To explore the clinical presentations, pathological features, imaging manifestation and genetic mutation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: A systematic study on the clinical manifestations, neuroimaging characteristics, pathology and molecular genetics was performed in the proband and 16 members of the family. An investigation on the hereditary pattern of the family tree of the proband was also conducted. RESULTS: The main clinical features including history of ischemic stroke attack, migraine, psychological disoders and dementia were noted. No risk factors of hypertension and arteriosclerosis were found. Pedigree maps of the index case were consistent with classical autosomal dominant inheritance. Subcortical multi-infarct lesions, leukoencephalopathy, O'Sullivan sign and ""Herringbone pattern""shape sign were observed via cranial MRI analysis. By electron microscopy, skin biopsy indicated the characteristic deposition of granular osmiophilic material (GOM) on the basement of smooth muscle cells of arterioles in the proband. The mutation of C144Y in the fourth exon of notch 3 gene was revealed in three cases, including 1 patient with normal MRI. CONCLUSION: The pedigree is diagnosed with CADASIL. The main cause can be attributed to a mutation of C144Y in the fourth exon of Notch 3 gene. The pedigree has enriched Chinese database of CADASIL.","Adult;CADASIL/ diagnosis/ genetics/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Pedigree;Receptors, Notch/ genetics","Chang, M. Z.;Wang, X. L.;Di, Z. L.;Zhang, L.;Zhang, W. P.;Li, Q.;Mao, J.;Qin, A. J.;Tian, Y.;Chen, H. L.",2011,Nov,,0,
5024,A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age,"OBJECTIVE: Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment. METHODS: Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls. RESULTS: Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter. CONCLUSIONS: The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.","0 (Anti-HIV Agents);30KYC7MIAI (Aspartic Acid);4L6452S749 (Inositol);997-55-7 (N-acetylaspartate);MU72812GK0 (Creatine);N91BDP6H0X (Choline);W8O17SJF3T (Memantine);AIDS Dementia Complex/diagnosis/drug therapy/ physiopathology;Adult;Age Factors;Anti-HIV Agents/therapeutic use;Aspartic Acid/ analogs & derivatives/metabolism;Basal Ganglia/drug effects/physiopathology;Brain/drug effects/ physiopathology;Brain Mapping;Choline/metabolism;Creatine/metabolism;Energy Metabolism/drug effects/ physiology;Female;Frontal Lobe/drug effects/physiopathology;HIV Seronegativity/physiology;HIV Seropositivity/physiopathology;Humans;Image Processing, Computer-Assisted;Inositol/metabolism;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Memantine/therapeutic use;Middle Aged;Parietal Lobe/drug effects/physiopathology;Reference Values;Treatment Outcome;Viral Load","Chang, L.;Lee, P. L.;Yiannoutsos, C. T.;Ernst, T.;Marra, C. M.;Richards, T.;Kolson, D.;Schifitto, G.;Jarvik, J. G.;Miller, E. N.;Lenkinski, R.;Gonzalez, G.;Navia, B. A.;Consortium, Hiv Mrs",2004,Dec,,0,
5025,A multicenter in vivo proton-MRS study of HIV-associated dementia and its relationship to age,"OBJECTIVE: Differences in diagnostic criteria and methods have led to mixed results regarding the metabolite pattern of HIV-associated brain injury in relation to neurocognitive impairment. Therefore, a multicenter MRS consortium was formed to evaluate the neurometabolites in HIV patients with or without cognitive impairment. METHODS: Proton magnetic resonance spectroscopy (MRS) at short-echo time (30 ms) was assessed in the frontal white matter, basal ganglia, and parietal cortex of 100 HIV patients [61 with AIDS dementia complex (ADC) and 39 neuroasymptomatic (NAS)] and 37 seronegative (SN) controls. RESULTS: Compared to SN, NAS had higher glial marker myoinositol-to-creatine ratio (MI/Cr) in the white matter (multivariate analyses, adjusted P=0.001), while ADC showed further increased MI/Cr in the white matter and basal ganglia (both P<0.001), and increased choline compounds (Cho)/Cr in white matter (P=0.04) and basal ganglia (P<0.001). Compared to NAS, ADC showed a reduction in the neuronal marker N-acetyl compound (NA)/Cr in the frontal white matter (P=0.007). CSF, but not plasma, viral load correlated with MI/Cr and Cho/Cr in white matter and NAA/Cr in parietal cortex. HIV infection and aging had additive effects on Cho/Cr and MI/Cr in the basal ganglia and white matter. CONCLUSIONS: The results suggest that glial activation occurs during the NAS stages of HIV infection, whereas further inflammatory activity in the basal ganglia and neuronal injury in the white matter is associated with the development of cognitive impairment. Aging may further exacerbate brain metabolites associated with inflammation in HIV patient and thereby increase the risk for cognitive impairment.","AIDS Dementia Complex [diagnosis] [drug therapy] [physiopathology];Age Factors;Anti-HIV Agents [therapeutic use];Aspartic Acid [analogs & derivatives] [metabolism];Basal Ganglia [drug effects] [physiopathology];Brain [drug effects] [physiopathology];Brain Mapping;Choline [metabolism];Creatine [metabolism];Energy Metabolism [drug effects] [physiology];Frontal Lobe [drug effects] [physiopathology];HIV Seronegativity [physiology];HIV Seropositivity [physiopathology];Image Processing, Computer-Assisted;Inositol [metabolism];Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Memantine [therapeutic use];Parietal Lobe [drug effects] [physiopathology];Reference Values;Treatment Outcome;Viral Load;Adult[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Chang, L.;Lee, P. L.;Yiannoutsos, C. T.;Ernst, T.;Marra, C. M.;Richards, T.;Kolson, D.;Schifitto, G.;Jarvik, J. G.;Miller, E. N.;Lenkinski, R.;Gonzalez, G.;Navia, B. A.",2004,,10.1016/j.neuroimage.2004.07.067,0,
5026,Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction,"BACKGROUND: Abnormalities in the white matter of the brain may occur in individuals with schizophrenia as well as with normal aging. Therefore, elderly schizophrenic patients may suffer further cognitive decline as they age. This study determined whether elderly schizophrenia participants, especially those with declined cognitive function (Clinical Dementia Rating score > 1), show white matter metabolite abnormalities on proton magnetic resonance spectroscopy and whether there are group differences in age-dependent changes in these brain metabolites. METHOD: Twenty-three elderly schizophrenia and twenty-two comparison participants fulfilling study criteria were enrolled. Localized, short echo-time (1)H MRS at 4 Tesla was used to assess neurometabolite concentrations in several white matter regions. RESULTS: Compared with healthy subjects, schizophrenia participants had lower N-acetyl compounds (-12.6%, p = .0008), lower myo-inositol (-16.4%, p = .026), and higher glutamate + glutamine (+28.7%, p = .0016) concentrations across brain regions. Schizophrenia participants with Clinical Dementia Rating >/= 1 showed the lowest NA in the frontal and temporal regions compared with control subjects. Interactions between age and schizophrenia status on total creatine and choline-containing compounds were observed; only schizophrenia participants showed age-related decreases of these metabolites in the right frontal region. CONCLUSIONS: Decreased NA in these white matter brain regions likely reflects reduced neuronal content associated with decreased synapses and neuronal cell volumes. The elevated glutamate + glutamine, if reflecting elevated glutamate, could result from excess neuronal glutamate release or glial dysfunction in glutamate reuptake. The decreased myo-inositol in participants with schizophrenia suggests decreased glial content or dysfunctional glia, which might result from glutamate-mediated toxicity.",Aged;Alanine/analogs & derivatives/metabolism;Brain/metabolism/*pathology;Brain Mapping;Choline/metabolism;Creatine/metabolism;Female;Glutamic Acid/metabolism;Glutamine/metabolism;Humans;Magnetic Resonance Imaging/methods;Magnetic Resonance Spectroscopy/methods;Male;Middle Aged;Neuroglia/*metabolism/*pathology;Protons;Schizophrenia/*pathology,"Chang, L.;Friedman, J.;Ernst, T.;Zhong, K.;Tsopelas, N. D.;Davis, K.",2007,Dec 15,10.1016/j.biopsych.2007.05.025,0,
5027,"Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naive HIV patients","This study aims to determine the relationship among cerebral metabolite concentrations (on proton magnetic resonance spectroscopy or (1)H MRS), cognitive function, and clinical variables (CD4, plasma and CSF viral loads, and lipids) in antiretroviral medication-nai;ve HIV patients. We hypothesized that the probable glial markers myo-inositol [MI] and choline compounds [CHO] would correlate with cognitive function, CD4 count, and viral loads, but not with serum lipids. Forty-five antiretroviral-drug-nai;ve HIV patients and 25 control subjects were evaluated. Frontal lobe [MI], [CHO], and total creatine [CR] were elevated, while basal ganglia [CR] were decreased, with increasing dementia severity. As a group, HIV patients showed slowing on fine motor (Grooved Pegboard) and psychomotor function (Trails A & B), and deficits on executive function (Stroop tasks). Lower CD4 counts and elevated plasma viral loads were associated with elevated frontal white matter [MI], which in turn correlated with the Stroop tasks. These findings suggest that systemic factors (resulting from suppressed immune function and higher plasma viral load) may lead to glial proliferation (elevated [MI], [CHO], and [CR]) in the frontal white matter, which in turn may contribute to deficits on executive function in HIV. Studying antiretroviral-nai;ve patients minimized the confounding effects of antiretroviral treatment on the clinical, MRS, and neuropsychological variables, and allowed for a more accurate assessment of the relationships among these measurements. Metabolite concentrations, rather than metabolite ratios, should be measured since [CR], a commonly used reference for metabolite ratios, varies with disease severity in both frontal lobe and basal ganglia.","AIDS Dementia Complex/*diagnosis/physiopathology;Adult;Aspartic Acid/*analogs & derivatives/metabolism;Basal Ganglia/pathology/physiopathology;Brain/pathology/*physiopathology;CD4 Lymphocyte Count;Cerebral Cortex/pathology/physiopathology;Choline/metabolism;Creatine/metabolism;Energy Metabolism/*physiology;Female;Humans;*Image Processing, Computer-Assisted;Inositol/metabolism;*Magnetic Resonance Imaging;*Magnetic Resonance Spectroscopy;Male;*Neuropsychological Tests;*Viral Load/classification","Chang, L.;Ernst, T.;Witt, M. D.;Ames, N.;Gaiefsky, M.;Miller, E.",2002,Nov,,0,
5028,Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex,"OBJECTIVE: To investigate the relation between biochemical alterations and disease severity in HIV-cognitive motor complex (HIV-CMC). BACKGROUND: HIV-CMC encompasses both the milder form (HIV-minor cognitive motor disorder [HIV-MCMD]) and the more severe form (HIV-dementia). There is no validated marker to monitor disease severity noninvasively. METHODS: A total of 54 patients with HIV-CMC (20 with HIV-MCMD, 34 with HIV-dementia) and 29 seronegative healthy volunteers were evaluated for cerebral metabolite abnormalities using proton (1H) MRS in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: The three subject groups showed different concentrations of myoinositol (MI; p = 0.0005) and choline-containing compounds (CHO; p = 0.004) in the frontal white matter. HIV-dementia patients had metabolite changes in all three brain regions whereas HIV-MCMD patients had abnormalities in the frontal white matter only. HIV-CMC patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in moderate to severe stages of dementia. Furthermore, CD4 count and CSF viral load, but not plasma viral load, showed significant effects on cerebral metabolite concentrations, which in turn showed significant effects on the HIV-dementia scale. CONCLUSIONS: In early stages of HIV-CMC, frontal white matter showed evidence of glial proliferation (with elevated MI and CHO levels) and cell membrane injury (with increased CHO levels), but no significant neuronal injury (with normal NA concentrations). HIV-MCMD and HIV-dementia patients have different neurochemical abnormalities. Because these biochemical alterations are related to clinical disease severity, they may be useful surrogate markers for noninvasive quantitative assessment of brain injury in patients with HIV-CMC.","AIDS Dementia Complex/diagnosis/*metabolism;Adult;Aged;Antigens, Viral/blood/cerebrospinal fluid;Choline/metabolism;Female;Frontal Lobe/metabolism/virology;*Hiv-1;Humans;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Motor Cortex/*metabolism/*virology;Severity of Illness Index;Viral Load","Chang, L.;Ernst, T.;Leonido-Yee, M.;Walot, I.;Singer, E.",1999,Jan 1,,0,
5029,Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex,"OBJECTIVE: To evaluate patients with early HIV-cognitive motor complex (HIV-CMC) for possible regional cerebral blood flow (rCBF) abnormalities on perfusion MRI (pMRI). BACKGROUND: Nuclear medicine techniques have demonstrated global and focal cerebral perfusion abnormalities in patients with HIV dementia. Ultrafast pMRI enables the measurement of rCBF throughout the brain without the need to apply radioactive tracers or ionizing radiation. METHODS: pMRI was used to measure the rCBF in 19 patients with early stages of HIV-CMC and 15 healthy seronegative control subjects. The rCBF maps were registered to high-resolution anatomic MRI scans and transformed into Talairach space. Statistical analysis of the rCBF maps was performed with SPM96. RESULTS: Compared with the control subjects, the patients with HIV had statistically significantly decreased rCBF bilaterally in the inferior lateral frontal cortices (right: -15%, p < 0.002; left: -12%, p < 0.005) and in the inferior medial parietal brain region (-15%, p < 0.0009). In contrast, rCBF was increased bilaterally in the posterior inferior parietal white matter (right: +19%, p < 0.0001; left: + 17%, p < 0.001). Furthermore, rCBF abnormalities correlated significantly with clinical disease severity as measured by CD4 count, plasma viral load, Karnofsky score, and HIV dementia scale. DISCUSSION: Our results are consistent with previous findings from PET and SPECT studies. Furthermore, pMRI can detect rCBF abnormalities that correlate with disease severity in HIV-CMC. Because pMRI is more cost-effective, faster, and safer than nuclear medicine techniques for monitoring rCBF changes, pMRI may be more feasible for monitoring the effects of therapy for HIV-CMC.",AIDS Dementia Complex/*diagnosis/physiopathology;Adult;Brain Mapping;Cerebral Cortex/blood supply/virology;*Cerebrovascular Circulation;Cognition Disorders/diagnosis/physiopathology/virology;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Motor Neurons/virology;Severity of Illness Index,"Chang, L.;Ernst, T.;Leonido-Yee, M.;Speck, O.",2000,Jan 25,,0,
5030,Impact of apolipoprotein E ε4 and HIV on cognition and brain atrophy: Antagonistic pleiotropy and premature brain aging,"Objective: The apolipoprotein E (APOE) ε4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOEε4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated. Methods: Automated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects]. Results: Compared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOEε4- subjects, SN controls with APOEε4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOEε4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (< 50 years) APOEε4. +. SN subjects had larger putamen and cerebral white matter, while younger APOEε4. +. HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-status × APOEε4 × Age) interaction-p-values = 0.005 to 0.03]. Interpretation: These findings suggest that APOEε4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOEε4 allele(s). Early screening for the APOEε4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results. © 2011 Elsevier Inc.",apolipoprotein E4;apolipoprotein E4 epsilon;Human immunodeficiency virus proteinase inhibitor;nonnucleoside reverse transcriptase inhibitor;RNA directed DNA polymerase inhibitor;unclassified drug;adult;aging;amygdaloid nucleus;article;brain;brain atrophy;brain cortex;brain function;brain size;caudate nucleus;CD4 lymphocyte count;cerebellum;cerebellum cortex;cognition;cognitive defect;controlled study;executive function;female;genotype;globus pallidus;hippocampus;HIV associated dementia;human;Human immunodeficiency virus infection;image analysis;Karnofsky Performance Status;learning;left hemisphere;major clinical study;male;memory;morphometrics;motor performance;neuropsychological test;nuclear magnetic resonance imaging;pleiotropy;premature brain aging;priority journal;putamen;right hemisphere;speed of information processing;subcortex;thalamus;verbal behavior;verbal fluency;white matter;working memory,"Chang, L.;Andres, M.;Sadino, J.;Jiang, C. S.;Nakama, H.;Miller, E.;Ernst, T.",2011,,,0,
5031,Impact of apolipoprotein E epsilon4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging,"OBJECTIVE: The apolipoprotein E (APOE) epsilon4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOEepsilon4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated. METHODS: Automated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects]. RESULTS: Compared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOEepsilon4- subjects, SN controls with APOEepsilon4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOEepsilon4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (<50 years) APOEepsilon4+SN subjects had larger putamen and cerebral white matter, while younger APOEepsilon4+HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-statusxAPOEepsilon4xAge) interaction-p-values=0.005 to 0.03]. INTERPRETATION: These findings suggest that APOEepsilon4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOEepsilon4 allele(s). Early screening for the APOEepsilon4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results.","AIDS Dementia Complex/ pathology/ psychology;Adult;Aged;Aging/physiology;Aging, Premature/etiology/ pathology;Apolipoprotein E4/ genetics;Atrophy;Brain/ pathology;Cognition/ physiology;Cognition Disorders/genetics/pathology;Female;Functional Laterality/physiology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Psychomotor Performance/physiology","Chang, L.;Andres, M.;Sadino, J.;Jiang, C. S.;Nakama, H.;Miller, E.;Ernst, T.",2011,Oct 15,10.1016/j.neuroimage.2011.07.010,0,
5032,Severity of White Matter Hyperintensities and Length of Hospital Stay in Patients with Cognitive Impairment: A CREDOS (Clinical Research Center for Dementia of South Korea) Study,"BACKGROUND & OBJECTIVE: White matter hyperintensities (WMHs) contribute to aggravation of dementia or geriatric syndrome, thereby resulting in functional impairment. However, evidence of direct association between WMHs and medical resource utilization indicated by length of hospital stay (LOS) is scarce in patients with cognitive impairment. This study aimed to examine the relationship between the severity of WMHs and LOS in patients with cognitive impairment. METHODS: 4,253 older adults with cognitive impairment were enrolled in this study. We defined LOS as the total sum of days from January 1, 2008 to December 31, 2012. The severity of periventricular (PVWMHs), deep (DWMHs), and overall white matter hyperintensities (Overall WMHs) was evaluated by a visual rating scale. We conducted multinomial logistic regression to demonstrate the relationship between LOS and severity of PVWHMs, DWHMs, and Overall WMHs, respectively. RESULTS: The median LOS was 20 days. Severe PVWMHs had a higher likelihood of longer LOS (Q3: odd ratio/OR = 1.32, 95% confidence interval/CI = 1.06-1.64; Q4: OR = 1.33, 95% CI = 1.07-1.65; Q5: OR = 1.55, 95% CI = 1.26-1.91). As for DWMHs, moderate DWMHs were related to longer LOS (Q4: OR = 1.33, 95% CI = 1.03-1.71; Q5: OR = 1.63, 95% CI = 1.26-2.11). Finally, severity of overall WMHs was independently associated with LOS, which was similar to the results of DWMHs. CONCLUSION: These findings would advocate for prevention of WMHs to stave off excess medical resource utilization in patients with cognitive impairment.","Aged;Aged, 80 and over;Cognition Disorders/*pathology/therapy;Female;Humans;*Length of Stay;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Republic of Korea/epidemiology;Retrospective Studies;White Matter/*pathology;Cognitive impairment;dementia;length of hospital stay;white matter hyperintensities","Chang, K. J.;Lee, S.;Lee, Y.;Lee, K. S.;Back, J. H.;Jung, Y. K.;Lim, K. Y.;Noh, J. S.;Kim, H. C.;Roh, H. W.;Choi, S. H.;Kim, S. Y.;Joon Son, S.;Hong, C. H.",2015,,10.3233/jad-142823,0,
5033,A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD,"OBJECTIVE: To investigate the patterns of MRI brain atrophy in patients with ALS with and without clinically evident frontotemporal lobar dementia (FTLD) using voxel-based morphometry (VBM). METHODS: Voxel-based morphometry was used to compare T1-weighted MRI images obtained from ten ALS patients with FTLD, ten ALS patients who were cognitively and behaviorally normal, and 22 control subjects. Images from patients and controls were spatially pre-processed using a study-specific, customized template and a priori images. A statistical threshold of p < 0.05 corrected for multiple comparisons determined significance. RESULTS: A common pattern of gray matter atrophy was seen in both ALS and ALS/FTLD patients when compared to controls that involved the bilateral motor/premotor cortices, the left middle and inferior frontal gyri, the anterior portion of the superior frontal gyri, the superior temporal gyri, the temporal poles and left posterior thalamus. Most of the frontal regions were significantly more atrophied in the ALS/FTLD group than in the ALS group. No significant differences were found in white matter volumes. CONCLUSIONS: Patients with ALS and ALS associated with frontotemporal lobar degeneration exhibit widespread gray matter atrophy in frontotemporal regions. This finding supports the idea of a clinical and anatomic continuum between ALS and frontotemporal lobar degeneration.","Adult;Age of Onset;Aged;Amyotrophic Lateral Sclerosis/ diagnosis/pathology/physiopathology;Atrophy/ diagnosis/pathology/physiopathology;Brain/ pathology/physiopathology;Brain Mapping/methods;Bulbar Palsy, Progressive/diagnosis/pathology/physiopathology;Cerebral Cortex/pathology/physiopathology;Comorbidity;Dementia/ diagnosis/pathology/physiopathology;Disease Progression;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neuropsychological Tests;Thalamus/pathology/physiopathology","Chang, J. L.;Lomen-Hoerth, C.;Murphy, J.;Henry, R. G.;Kramer, J. H.;Miller, B. L.;Gorno-Tempini, M. L.",2005,Jul 12,10.1212/01.wnl.0000167602.38643.29,0,
5034,Evaluation of the development of vascular dementia following lacunar infarctions: New vascular events may speed up the deterioration of vascular cognitive disorder,"Aim: To evaluate the cognitive and behavioral course in patients with probable VaD-L, and the affection when they suffered new vascular events during follow-up. Methods: Totally 72 patients with vascular dementia after lacunae cerebral infarction were selected from Neurological Department of Shanghai Huadong Hospital from January 1999 to June 2004. Among them, there were 54 males and 18 females with the average age of (73±7) years. All patients were given aspirin (75 mg/time, once per day), huperzine A (0.05 mg/pill, 2 pillsonce, twice per day) and piracetam (0.4 g/pill, 2 pills/time, 3 times per day).The follow-up was lasted from 1999 to 2001 with 4 months as a cycle and the average time was (24.25±6.01) months. The vascular events included the new vascular episode of brain and heart during the follow up. All patients were tested with CT or MRI, MMSE, NPI and ADL. And according to who did or did not undergo additional vascular episodes, all patients were randomized into 2 groups. Results: Totally 72 cases entered the final analysis. 1 Scores of MMSE were decreased as compared with those before follow up, but those of NPI and ADL were increased after the follow up [(22.3±4.6, 32.1±18.3, 43.7±9.6); (25.3±5.2, 19.4±13.9, 32.6±8.3), (t=5.67-14.86, P < 0.01)]. 2 Scores of MMSE, NPI and ADL in vascular-event occurrence group were deteriorated obviously as compared with those in vascular-event unoccurrence group [(-2.24±1.4, 11.60±14.3, 9.88±12.5); (-1.03±1.7, 2.35±15.6, 2.04±7.3), (t=2.94-7.38, P < 0.01)]. 3 Cognition and behavior deterioration were related with the level of vascular-event occurrence (r=0.920, P <0.01), and cognitive changes were obviously positive related with behavior changes (r=0.793, P < 0.01). Conclusion: VaD-L is characterized by cognitive and behavioral decline. The rate of decline is determined mainly by the occurrence of new vascular episodes. The underlying pathological processes affecting the brain and the severity of the cognitive and the behavioral impairments.",acetylsalicylic acid;huperzine A;piracetam;aged;article;behavior;behavior disorder;brain infarction;brain ventricle;cognition;cognitive defect;computer assisted tomography;controlled study;disease course;disease severity;drug dose regimen;female;follow up;human;major clinical study;male;Mini Mental State Examination;multiinfarct dementia;nuclear magnetic resonance imaging;aspirin,"Chang, J.;Wei, W. S.;Li, Y. J.",2005,,,0,
5035,Hyperbaric oxygen ameliorates delayed neuropsychiatric syndrome of carbon monoxide poisoning,"OBJECTIVES: Delayed neuropsychiatric syndrome (DNS) is characterized by mental impairment, motor dysfunction, dementia, or psychosis that develops between a few days and weeks after acute carbon monoxide (CO) poisoning. One possible mechanism responsible for CO-mediated encephalopathy involves oxidative stress, such as lipid peroxidation, caused by the cellular uptake of CO and which leads to an inflammatory cascade. There is no current effective treatment for DNS. We applied 8-40 sessions of hyperbaric oxygen therapy (HBO2) to patients with DNS and evaluated its effectiveness. METHODS: After admission, all patients were administered piracetam or bromocriptine, or both, and received HBO2. Neuropsychiatric tests included EEG, mini-mental status examination (MMSE), brain MRI, event-related potential (ERP), and brain perfusion scan (brain SPECT). Results of these tests were compared before and after HBO2, and the clinical features were monitored during this period. RESULTS: The symptoms of DNS for all patients improved significantly after HBOT. Although white matter changes remained evident in the brain MRI scans, other examinations such as EEG, MMSE, ERP, and 99mTc-ECD brain SPECT were nearly normal after HBOT. CONCLUSION: Our results suggest that HBO2 decreases the severity of impairment in patients with DNS. Although a large randomized trial is required to address the efficacy of this therapy, therapeutic application of HBO2 may be recommended in patients with DNS after CO poisoning.",adult;article;carbon monoxide intoxication;dementia;female;human;hyperbaric oxygen;male;mental disease;middle aged;motor dysfunction;nuclear magnetic resonance imaging;psychosis;syndrome,"Chang, D. C.;Lee, J. T.;Lo, C. P.;Fan, Y. M.;Huang, K. L.;Kang, B. H.;Hsieh, H. L.;Chen, S. Y.",2010,,,0,
5036,'The spectrum of vascular dementia'--a retrospective study from South India,"OBJECTIVES: Vascular dementia (VaD) is high in Indian population and is preventable to some extent but there is paucity of literature. Hence we decided to study the clinical and laboratory spectrum of VaD. METHODS: It was retrospective hospital based study. The patients who satisfied Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV criteria) for VaD and age of more than 40 years were identified on the basis of case file code which is uniformly used by the hospital. RESULTS: Of the 83 patients included, 72.3% (60) were males (mean age: 65.3 +/- 8.6 years) and 27.3% (23) females (mean age: 65.7 +/- 1.1 years). Mean age of the patients was 65.4 +/- 9.2 years. Abrupt onset was seen in 42 (51%) patients and 41 (49%) had insidious onset. There was gradual progression in 48 (57.8%), stepwise progression in 33 (39.8%) and 2 patients had rapid progression. Naming impairment was seen in 64 (77.1%), visuospatial disorientation was present in 49 (59%), dyscalculia in 55 (66.3%), emotional lability in 26.5%. Hypertension was the single most important risk factor (71.1%) followed by smoking (46.9%) and dyslipidaemia (45.8%). Neuropsychological testing showed Executive function involvement in 18 (66.7%) followed by memory in 16 (59.3%) patients. The total white matter hyperintensity score (12.39 +/- 6.73) significantly correlated with mini mental scores (r: -0.4; p: 0.02). CONCLUSION: We found that in our patients with vascular dementia, gradual progression, naming impairment and small vessel disease in imaging were the most common abnormalities. Hypertension was the single most important risk factor.","Aged;Aged, 80 and over;Dementia, Vascular/ diagnosis;Female;Humans;India;Male;Middle Aged;Retrospective Studies","Chandra, S. R.;Yadav, R.;Puneeth, C. S.;Saini, J.;Issac, T. G.",2014,Jun,,0,
5037,Syndromes of Rapidly Progressive Cognitive Decline-Our Experience,"BACKGROUND: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. AIMS: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center. SETTINGS AND DESIGN: Patients who presented with rapid deterioration of cognitive functions within weeks to 1 year between 2011 and December 2016 were evaluated. PATIENTS AND METHODS: All patients underwent all mandatory tests for dementia including brain imaging. Complete vasculitis workup, autoimmune encephalitis profile including Voltage Gated Potassium Channel, N-methyl-D-aspartic acid receptor, glutamic acid-decarboxylase, thyroid-peroxidase antibody, cerebrospinal fluid, and other special tests such as duodenal biopsy and paraneoplastic workup were done based on clinical indications. RESULTS AND CONCLUSIONS: Out of 144 patients 42 had immune-mediated encephalopathy, 18 had Creutzfeldt-Jakob disease, 3 had Vitamin B12 deficiency, 63 had infection with neurocysticercosis, 7 had tuberculosis, 2 had HIV, 1 had herpes simplex encephalitis, 1 had neurosyphilis, 1 Whipples disease, 1 had Subacute Sclerosing Panencephalitis, 1 had Mass lesion, 3 had Frontotemporal dementia, and 3 had small vessel disease. Good majority of these patients have infective and immune-mediated causes and less number belong to degenerative group. Therefore, caution is needed to look for treatable cause as it carries a different treatment options and outcome.",Degenerations;immune-mediated;infections;nutritional;rapidly progressive dementia,"Chandra, S. R.;Viswanathan, L. G.;Pai, A. R.;Wahatule, R.;Alladi, S.",2017,Aug,,0,
5038,Role of amyloid from a multiple sclerosis perspective: a literature review,"The traditional concept of multiple sclerosis (MS), that it is primarily a white matter inflammatory disease, has changed a great deal. Thanks to the recent development witnessed in MS research, a whole new idea has emerged that MS is a neurodegenerative disease, and neurodegeneration occurs rather earlier in the pathological process. This has also led to the foundation of the hypothesis that two fundamentally different diseases, Alzheimer's disease (AD) and MS, may share a common mechanism of neurodegeneration. Conventionally, amyloid is thought to be a consequence of protein misfolding and aggregation and is most notorious for its association with debilitating and chronic human diseases. Amyloid is implicated to be related with the deterioration and progression of AD. The finding of amyloid precursor protein expression in axons around the plaque in MS, as well as the correlation of amyloid-beta (Abeta) with different stages of MS, has clearly indicated that amyloid plays some kind of key role in MS disease pathogenesis. Excitingly, a paradoxical phenomenon of Abeta has also been observed in several studies recently. It has been shown that amyloid might actually be helping in ameliorating the inflammatory effect in diseases like AD and MS. Amyloid imaging allows earlier diagnosis of MS by taking advantage of the relation of amyloid with MS. This will have a big impact on patient diagnosis and management. In this review I have included the findings of research studies dating from several years back to the most recent ones. Through this review I have tried to show the critical role of amyloid in MS and the importance of investigating through PET imaging.",,"Chandra, A.",2015,,10.1159/000375309,0,
5039,Atrial Fibrillation is Independently Associated with Cognitive Impairment after Ischemic Stroke,"BACKGROUND: While atrial fibrillation (AF) is an important risk factor for ischemic strokes and mild cognitive impairment (MCI) in Alzheimer's disease, the association between AF and post-stroke cognitive impairment (PSCI), and the factors mediating this association, is unclear. OBJECTIVE: To investigate the role of AF in PSCI, especially in relation to other markers of cerebrovascular disease. METHODS: 445 subjects with mild ischemic stroke without pre-stroke cognitive decline were assessed 3-6 months post-stroke for cognitive deficits. MRIs were reviewed by trained raters for acute infarct characteristics, global cortical atrophy, white matter hyperintensities, cerebral microbleeds, and intracranial stenosis. Logistic regression analysis was used to identify factors independently associated with PSCI. Subjects were also categorized according to paroxysmal (pAF) or persistent/chronic AF (p/cAF), and presence or absence of AF or large cortical infarcts (LCI) to study cognitive trends. RESULTS: 80 (18.0%) subjects had AF. 76.3% of AF subjects and 42.7% of subjects without AF had PSCI. The odds ratio (OR) of AF in developing PSCI was 2.31 (95% CI: 1.12-4.75; p = 0.035), after correcting for other risk factors. pAF subjects and AF subjects with LCIs had higher ORs for PSCI. AF subjects performed worse in neuropsychological tasks associated with global cognition, episodic memory, and executive function. CONCLUSION: AF is a significant risk factor for PSCI, even after correcting for AF-related infarcts. Other mechanisms, such as hypoperfusion, microhemorrhages, and neuroinflammation, may be at play. All stroke patients with AF, regardless of the type of infarction, should be closely monitored for PSCI.",Atrial fibrillation;cognitive impairments;ischemic stroke;magnetic resonance imaging;risk factors,"Chander, R. J.;Lim, L.;Handa, S.;Hiu, S.;Choong, A.;Lin, X.;Singh, R.;Oh, D.;Kandiah, N.",2017,,,0,
5040,Multiple cerebral infarcts associated with an atrial septal aneurysm - Superimposed thrombus detected by transesophageal echocardiography,The authors describe the case of a patient referred for evaluation of multiinfarct dementia. Conventional echocardiography revealed an aneurysm of the interatrial septum. A transesophageal echocardiogram demonstrated surimposed thrombus. This rare cause of systemic emboli can be diagnosed only by transesophageal echocardiography and is of major interest to avoid recurrence of ischemic strokes.,aged;article;brain infarction;case report;cerebrovascular accident;computer assisted tomography;female;heart aneurysm;heart atrium septum;human;multiinfarct dementia;nuclear magnetic resonance imaging;thromboembolism;thrombus;transesophageal echocardiography,"Chammas, E.;Trinca, M.;Goullard, L.;Leys, D.;Houdas, Y.",1995,,,0,
5041,Pediatric AIDS: a longitudinal comparative MRI and CT brain imaging study,"Fourteen consecutive children with acquired immune deficiency syndrome (AIDS) (age range, 4 months to 11 years; median 4 years) were studied prospectively comparing nonenhanced cranial magnetic resonance imaging (MRI) and computed tomographic (CT) scans. MRI and CT were performed twice: at time of entry into protocol and again at 1 year. In addition, sequential neurologic (every 2 months) and neuropsychological examinations (every 6 months) were performed. At entry, 12 children had abnormal neurologic examinations; of these, 10 had developmental delay; two children were normal by developmental history and neurologic examination. Five children performed in the normal range on a standardized neuropsychological test, whereas nine children showed significant delays in verbal or motor/perceptual development. Following 1 year of study, four children had normal and six had abnormal neurologic examinations (six stable and four improved). Neuropsychological examinations were normal in five children and abnormal in five (seven stable, one improved, and two deteriorated). At entry, the following neuroradiographic abnormalities were seen: brain parenchymal volume loss (eight, MR = CT), cervical lymphatic enlargement (four, MR = CT), striatal-thalamic calcification (one, CT > MR), delayed myelination (one, MR > CT), and focal white-matter lesions (one, MR > CT). At 1 year the following neuroradiographic changes were seen: brain parenchymal volume loss (10, MR = CT; two improved, eight stable); cervical lymphatic enlargement (one, MR = CT; three improved, one stable), striatal-thalamic calcification (one, CT > MR; one new), and focal white-matter lesions (one, MR > CT; one stable).(ABSTRACT TRUNCATED AT 250 WORDS)","AIDS Dementia Complex/ diagnosis/pathology;Brain/pathology;Child;Child, Preschool;Electroencephalography;Female;Humans;Infant;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Tomography, X-Ray Computed","Chamberlain, M. C.",1993,Apr,,0,
5042,APOE ε4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of Aβ protein,"The relative amounts of amyloid β-protein (Aβ) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic and environmental determinants are still unclear, as are the functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E (ApoE), influence the risk of developing AD and of deposition of Aβ within the brain. We examined the relationship between the APOE genotype and the relative extent of accumulation of Aβ as plaques within the cerebral parenchyma and in cortical blood vessels in the form of cerebral amyloid angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly, neurologically normal controls of which 19 had CAA without other neuropathological features of AD. In the AD cases, we also assessed whether the severity of CAA was related to the age of onset and duration of dementia, risk factors for atherosclerotic vascular disease, and histologically demonstrable cerebral in-farcts or foci of haemorrhage. The APOE genotype was determined by a standard polymerase chain reaction-based method. Paraffin sections of frontal, temporal and parietal lobes were immunolabelled for Aβ and the parenchymal Aβ load (total Aβ minus vessel-associated Aβ) was quantified by computer-assisted image analysis. CAA severity was scored for cortical and leptomeningeal vessels. The relevant clinical data were obtained from the database of the South West Brain Bank. In AD, we found the severity of CAA to be strongly associated with the number of ε4 alleles (P < 0.0001) but the parenchymal Aβ load to be independent of APOE genotype. Cases with severe CAA had a lower parenchymal Aβ load than had those with moderate CAA (P = 0.003). Neither the severity of CAA nor the parenchymal Aβ load correlated with age of onset, duration of disease or age at death, and the severity of CAA also did not correlate with the presence of cerebral infarcts or foci of haemorrhage. These findings indicate that possession of the APOE ε4 allele favours vascular over parenchymal accumulation of Aβ in AD. This may influence the pathogenesis of neurodegeneration in ε4-associated AD.",,"Chalmers, K.;Wilcock, G. K.;Love, S.",2003,June,,0,
5043,Increase of white matter string vessels in Alzheimer's disease,"String vessels are collagenous structures connected to capillaries. They have no endothelial cells or lumen. We assessed collagen IV-labeled string vessels in the white matter (WM) of subjects with Alzheimer's disease (AD) (n = 12) and non-AD controls (n = 11) using 100 microm celloidin sections. Ten standard fields were digitally captured and the number and length of normal vessels and string vessels were quantified by computerized image analysis. The WM of the AD-diagnosed individuals contained more strings per mm2 (3.95 +/- 0.49) than comparable WM from controls (1.36 +/- 0.39) (p = 0.0005) and had increased total string vessel length in mm/mm2 (AD = 0.29 +/- 0.04; control = 0.10 +/- 0.03; p = 0.0015). There was a 25% increase (not statistically significant) in vessel density in mm/mm2 in AD subjects (AD = 11.88 +/- 0.87; control = 9.53 +/- 0.78; p = 0.06), presumably due to brain atrophy in the white matter. Although vessel length was slightly increased in AD subjects, they still had more than double the string length per total vessel length (AD = 2.88 +/- 0.38) compared to controls (1.36 +/- 0.27) (p = 0.0057). This increase in string vessels in the white matter of AD subjects suggests a decrease in vascular supply in this disease.","Aged;Aged, 80 and over;Alzheimer Disease/metabolism/ pathology;Arterioles/anatomy & histology;Atrophy/pathology;Brain/ blood supply/metabolism/ pathology;Capillaries/anatomy & histology;Female;Humans;Male;Middle Aged","Challa, V. R.;Thore, C. R.;Moody, D. M.;Anstrom, J. A.;Brown, W. R.",2004,Aug,,0,
5044,Thyroid function and the risk of dementia: The Rotterdam Study,"OBJECTIVE: To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. METHODS: Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. RESULTS: We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. CONCLUSIONS: High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia.",9002-71-5 (Thyrotropin);Q51BO43MG4 (Thyroxine);Aged;Brain/ diagnostic imaging;Cardiovascular Diseases/blood/diagnostic imaging/epidemiology;Cross-Sectional Studies;Dementia/ blood/ diagnostic imaging/epidemiology;Follow-Up Studies;Humans;Incidence;Magnetic Resonance Imaging;Middle Aged;Prospective Studies;Risk Factors;Sensitivity and Specificity;Thyroid Gland/metabolism;Thyrotropin/ blood;Thyroxine/ blood,"Chaker, L.;Wolters, F. J.;Bos, D.;Korevaar, T. I.;Hofman, A.;van der Lugt, A.;Koudstaal, P. J.;Franco, O. H.;Dehghan, A.;Vernooij, M. W.;Peeters, R. P.;Ikram, M. A.",2016,Oct 18,,0,5045
5045,Thyroid function and the risk of dementia: The Rotterdam Study,"OBJECTIVE: To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. METHODS: Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. RESULTS: We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. CONCLUSIONS: High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia.",,"Chaker, L.;Wolters, F. J.;Bos, D.;Korevaar, T. I.;Hofman, A.;van der Lugt, A.;Koudstaal, P. J.;Franco, O. H.;Dehghan, A.;Vernooij, M. W.;Peeters, R. P.;Ikram, M. A.",2016,Sep 16,10.1212/wnl.0000000000003227,0,
5046,Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging,"Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (beta = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders.",Brain microstructural organization;Brain morphology;Diffusion tensor imaging;Thyroid function,"Chaker, L.;Cremers, L. G. M.;Korevaar, T. I. M.;de Groot, M.;Dehghan, A.;Franco, O. H.;Niessen, W. J.;Ikram, M. A.;Peeters, R. P.;Vernooij, M. W.",2018,Jan,,0,
5047,Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia,"Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case-control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community. All subjects underwent detailed neuropsychological assessment, 3-Tesla magnetic resonance imaging, and venous blood draw. Subjects were classified as CIND or AD based on clinical criteria, while significant CeVD was defined as the presence of cortical infarcts and/or 2 lacunes or more, and/or confluent white matter hyperintensities (WMHs) in 2 or more brain regions. A total of 324 subjects were included in the study, of whom 80 had no cognitive impairment, 144 CIND and 100with AD. Higher GDF-15 levels were significantly associated with disease groups, especially in the presence of CeVD, namely, CIND with CeVD (odds ratios [OR]: 7.21; 95% confidence interval [CI]: 2.14-24.27) and AD with CeVD (OR: 21.87; 95% CI: 2.01-237.43). Among the different CeVD markers, only WMH was associated with higher GDF-15 levels (OR: 3.97; 95% CI: 1.79-8.83). The associations between GDF-15 and cognitive impairment as well as with WMH remained significant after excluding subjects with cardiovascular diseases. In conclusion, we showed that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH.",,"Chai, Y. L.;Hilal, S.;Chong, J. P.;Ng, Y. X.;Liew, O. W.;Xu, X.;Ikram, M. K.;Venketasubramanian, N.;Richards, A. M.;Lai, M. K.;Chen, C. P.",2016,Aug,10.1097/md.0000000000004566,0,
5048,The cerebellum and cognitive function: Implications for rehabilitation,"Objective: To characterize the cognitive effects of isolated cerebellar lesions. Design: Review of two inpatient cases. Setting: The rehabilitation unit of a tertiary general hospital. Patients or Other Participants: Two patients with acute ischemic strokes who had solitary cerebellar infarcts. Intervention: Assessment with standard neuropsychological tests norms. A classical conditioning eyeblink paradigm was performed. Main Outcome Measures: Neuropsychological measures of intellectual and executive functions, learning and memory, visual-spatial abilities, language functioning, fine motor speed, and dexterity. Results: Test findings suggested lesion-associated deficits in higher aspects of cognition (visuospatial reasoning, verbal and visual memory, and intellectual and executive functions). These functions are not usually associated with the fundamentally motoric role of the cerebellum. Conclusions: (1) Lesions in the cerebellum can be associated with impairments in higher cognitive functioning. (2) Such effects may be severe enough for a diagnosis of dementia under current diagnostic criteria. (3) These rehabilitation patients may benefit from comprehensive cognitive examination to determine if cognitive effects will detract from their participation. (4) Further research is needed to localize which cerebellar areas affect which cognitive abilities.",aged;article;case report;cerebellum infarction;cerebellum injury;cerebrovascular accident;clinical feature;cognitive defect;dementia;Doppler echography;female;human;intelligence test;language test;male;memory;neuropsychological test;nuclear magnetic resonance imaging,"Chafetz, M. D.;Friedman, A. L.;Kevorkian, C. G.;Levy, J. K.",1996,,,0,
5049,Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arterial disease of the brain recently mapped to chromosome 19. We studied 148 subjects belonging to seven families by magnetic resonance imaging and genetic linkage analysis. 45 family members (23 males and 22 females) were clinically affected. Frequent signs were recurrent subcortical ischaemic events (84%), progressive or stepwise subcortical dementia with pseudobulbar palsy (31%), migraine with aura (22%), and mood disorders with severe depressive episodes (20%). All symptomatic subjects had prominent signal abnormalities on MRI with hyperintense lesions on T2-weighted images in the subcortical white-matter and basal ganglia which were also present in 19 asymptomatic subjects. The age at onset of symptoms was mean 45 (SD [10-6]) years, with attacks of migraine with aura occurring earlier in life (38.1 [8.03] years) than ischaemic events (49.3 [10.7] years). The mean age at death was 64.5 (10.6) years. On the basis of MRI data, the penetrance of the disease appears complete between 30 and 40 years of age. Genetic analysis showed strong linkage to the CADASIL locus for all seven families, suggesting genetic homogeneity. CADASIL is a hereditary cause of stroke, migraine with aura, mood disorders and dementia. The diagnosis should be considered not only in patients with recurrent small subcortical infarcts leading to dementia, but also in patients with transient ischaemic attacks, migraine with aura or severe mood disturbances, whenever MRI reveals prominent signal abnormalities in the subcortical white-matter and basal ganglia. Clinical and MRI investigations of family members are then crucial for the diagnosis which can be confirmed by genetic linkage analysis. The disease is probably largely undiagnosed.",Adult;Age of Onset;Aged;Brain Ischemia/diagnosis/genetics;Cerebral Infarction/diagnosis/ genetics;Cerebrovascular Disorders/diagnosis/ genetics;Dementia/genetics;Diffuse Cerebral Sclerosis of Schilder/diagnosis/ genetics;Female;Genetic Linkage;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Migraine Disorders/genetics;Mood Disorders/genetics;Pedigree;Syndrome,"Chabriat, H.;Vahedi, K.;Iba-Zizen, M. T.;Joutel, A.;Nibbio, A.;Nagy, T. G.;Krebs, M. O.;Julien, J.;Dubois, B.;Ducrocq, X.;et al.",1995,Oct 7,,0,
5050,Autosomal dominant migraine with MRI white-matter abnormalities mapping to the CADASIL locus,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant cerebral arteriopathy mapped to chromosome 19 and characterized mainly by recurrent subcortical ischemic strokes and extensive white-matter signal abnormalities (WMAs) on magnetic resonance imaging. Other clinical features include migraine attacks and progressive subcortical dementia. Herein, we describe several members of the same family who suffered migraine attacks, mostly with aura, associated with WMAs, segregating with an autosomal dominant pattern of inheritance. One individual had a progressive subcortical dementia with similar WMAs. Although ischemic stroke, one of the hallmarks of CADASIL, was not present in this family, we hypothesized that the present disorder resulted from an alteration of the CADASIL gene. Genetic linkage analysis, using four chromosome 19 markers spanning the CADASIL locus, supports this hypothesis.",,"Chabriat, H.;Tournier-Lasserve, E.;Vahedi, K.;Leys, D.;Joutel, A.;Nibbio, A.;Escaillas, J. P.;Iba-Zizen, M. T.;Bracard, S.;Tehindrazanarivelo, A.;Gastaut, J. L.;Bousser, M. G.",1995,June,,0,
5051,Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI,"BACKGROUND AND PURPOSE: CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood. METHODS: To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale. RESULTS: We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects. CONCLUSIONS: These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.","Adult;Aged;Analysis of Variance;Brain/ pathology;Brain Mapping;Case-Control Studies;Dementia, Multi-Infarct/ pathology;Diffusion;Extracellular Space;Humans;Magnetic Resonance Imaging/ methods;Middle Aged","Chabriat, H.;Pappata, S.;Poupon, C.;Clark, C. A.;Vahedi, K.;Poupon, F.;Mangin, J. F.;Pachot-Clouard, M.;Jobert, A.;Le Bihan, D.;Bousser, M. G.",1999,Dec,,0,
5052,Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking,"BACKGROUND: White matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are underlaid by severe ultrastructural changes of the arteriolar wall. Although chronic ischemia is presumed to cause the tissue lesions, the pattern of perfusion abnormalities and hemodynamic reserve in CADASIL, particularly within the white matter, remains unknown. METHODS: We used the MRI bolus tracking method in 15 symptomatic patients with CADASIL (5 with dementia) and 10 age-matched control subjects before and 20 minutes after the intravenous injection of acetazolamide (ACZ, 17 mg/kg). Cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT) were calculated both in the cortex and in the white matter according to the singular value decomposition technique. Perfusion parameters were obtained in regions of hyperintensities and within the normal-appearing white matter as observed on T2-weighted images. Analysis was performed with both absolute and relative (region/whole brain) values. RESULTS: A significant reduction in absolute and relative CBF and CBV was found within areas of T2 hyperintensities in white matter in the absence of significant variations of MTT. This reduction was more severe in demented than in nondemented patients. No significant change in absolute CBF and CBV values was observed in the cortex of patients with CADASIL. A decrease in relative CBF and CBV values was detected in the occipital cortex. After ACZ administration, CBF and CBV increased significantly in both the cortex and white matter of affected subjects, but the increase in absolute CBF was lower within areas of increased signal on T2-weighted images in patients than in the white matter of control subjects. CONCLUSIONS: In CADASIL, both basal perfusion and hemodynamic reserve are decreased in areas of T2 hyperintensities in the white matter. This hypoperfusion appears to be related to the clinical severity. The significant effect of ACZ on CBF and CBV suggests that cerebral perfusion might be increased using pharmacological vasodilation in CADASIL.","Acetazolamide/ administration & dosage;Adult;Blood Flow Velocity/drug effects;Brain/ blood supply/drug effects/pathology;Carbonic Anhydrase Inhibitors/ administration & dosage;Cerebrovascular Circulation/drug effects/ physiology;Dementia, Multi-Infarct/diagnosis/drug therapy/ physiopathology;Echo-Planar Imaging;Female;Humans;Injections, Intravenous;Male;Middle Aged;Observer Variation","Chabriat, H.;Pappata, S.;Ostergaard, L.;Clark, C. A.;Pachot-Clouard, M.;Vahedi, K.;Jobert, A.;Le Bihan, D.;Bousser, M. G.",2000,Aug,,0,
5053,Patterns of MRI lesions in CADASIL,"OBJECTIVE: To investigate the location and severity of MRI signal abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: One hallmark of this arteriopathy due to mutations of Notch 3 gene is the presence of MRI signal abnormalities in both symptomatic and asymptomatic patients. METHODS: MRIs of 75 patients (43 with symptoms) were reviewed by a neuroradiologist masked to their clinical status. After assessing the presence of MRI lesions on T1- and T2-weighted images (T1-WI, T2-WI) in different subcortical regions, the severity of hyperintensities on T2-WI was scored using a global rating scale and a regional semiquantitative scale in the periventricular white matter (PV), deep white matter (WM), basal ganglia (BG), and infratentorial areas (IT). RESULTS: Sixty-eight patients (90%) had hyperintensities on T2-WI located in the white matter, more frequent in PV (96%) and WM (85%) than in the superficial white matter (25%). Hyperintensities also occurred in BG (60%) and brainstem (45%). Forty-seven patients (62%) presented with hypointensities on T1-WI. In one-third of the affected individuals, white matter hyperintensities occurred in the absence of small deep infarcts on T1-WI. The frequency and severity scores calculated for PV, WM, BG, or IT hyperintensities increase dramatically with age. These scores were higher in symptomatic compared with asymptomatic gene carriers. Dementia, Rankin score > 1, or both occurred only in the presence of diffuse white matter signal abnormalities. CONCLUSION: Our results suggest that different subcortical areas have different vulnerabilities to ischemia in CADASIL. The age effect we observed may show an accumulation of lesions with aging during the course of the disease. A prospective study is needed to investigate if the rating of MRI lesions is of prognostic value in CADASIL.","Adult;Analysis of Variance;Brain Diseases/ diagnosis/genetics;Cerebral Arterial Diseases/diagnosis;Dementia, Multi-Infarct/diagnosis;Female;Genes, Dominant;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis;Male;Middle Aged;Mutation;Risk Factors;Signal Processing, Computer-Assisted","Chabriat, H.;Levy, C.;Taillia, H.;Iba-Zizen, M. T.;Vahedi, K.;Joutel, A.;Tournier-Lasserve, E.;Bousser, M. G.",1998,Aug,,0,
5054,Predictors of Clinical Worsening in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Prospective Cohort Study,"BACKGROUND AND PURPOSE: Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy remain unknown. This study aims to identify demographic, clinical, and magnetic resonance imaging predictors of incident strokes, incident dementia, clinical deterioration, and death in patients with this genetically proven disease. METHODS: Two hundred ninety subjects (mean age, 50.6+/-11.4 years) were assessed at baseline and followed up for 36 months. Incident clinical events were recorded, and clinical scores included the Mini Mental State Examination, Mattis Dementia Rating Scale, modified Rankin Scale, and Barthel index. The number of lacunes and microbleeds, the volume of white-matter hyperintensities, and brain parenchymal fraction were assessed on baseline magnetic resonance imaging. Data were analyzed by ANCOVA, multivariable logistic regression, and Cox proportional hazard models. RESULTS: Incident stroke occurred in 55 of 278 patients (19.8%). Moderate or severe disability developed in 19 of 210 (9%) nondisabled individuals, incident dementia in 49 of 231 (20%) nondemented subjects, and 4.8% of patients died. Active smoking, the number of lacunes, and brain parenchymal fraction independently predicted incident stroke during follow-up. Gait disturbance, dementia, and brain parenchymal fraction predicted progression toward moderate or severe disability. Active smoking, disability, and brain parenchymal fraction predicted incident dementia. Age was the only significant predictor of death. CONCLUSIONS: Clinical assessment and brain magnetic resonance imaging aid in predicting incident clinical events and clinical deterioration in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. There is a bidirectional relationship between dementia and moderate or severe disability in predicting each other's onset. Active smoking is a modifiable risk factor associated with clinical progression in Notch3 mutation carriers.",,"Chabriat, H.;Herve, D.;Duering, M.;Godin, O.;Jouvent, E.;Opherk, C.;Alili, N.;Reyes, S.;Jabouley, A.;Zieren, N.;Guichard, J. P.;Pachai, C.;Vicaut, E.;Dichgans, M.",2016,Jan,10.1161/strokeaha.115.010696,0,
5055,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,,"CADASIL/*genetics/history/*pathology/therapy;Cognition Disorders/diagnosis/etiology;*Genes, Dominant;History, 20th Century;Humans;Magnetic Resonance Imaging/methods;Migraine with Aura/etiology;Receptors, Notch/genetics","Chabriat, H.;Bousser, M. G.",2008,,10.1016/s0072-9752(07)01261-4,0,
5056,Neuropsychiatric manifestations in CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease of mid-adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter lesions associated with lacunar infarctions in various subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as ""subcortical ischemic vascular dementia."" Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain. © 2007, LLS SAS.",,"Chabriat, H.;Bousser, M. G.",2007,2007,,0,
5057,[CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): a new genetic disease of the cerebral arteries associated with vascular leukoencephalopathies] CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): une nouvelle maladie genetique des arteres cerebrales au sein des leucoencephalopathies d'origine vasculaire,,"Brain/blood supply/pathology;Cerebrovascular Disorders/physiopathology;Dementia, Multi-Infarct/ genetics/pathology;Diagnosis, Differential;Humans;Leukoencephalopathy, Progressive Multifocal/ physiopathology;Magnetic Resonance Imaging","Chabriat, H.;Bousser, M. G.",2000,Mar 15,,0,
5058,[CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy): a new genetic disease of the cerebral arteries associated with vascular leukoencephalopathies],,"Brain/blood supply/pathology;Cerebrovascular Disorders/physiopathology;Dementia, Multi-Infarct/*genetics/pathology;Diagnosis, Differential;Humans;Leukoencephalopathy, Progressive Multifocal/*physiopathology;Magnetic Resonance Imaging","Chabriat, H.;Bousser, M. G.",2000,Mar 15,,0,
5059,[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy] Cadasil,"CADASIL is an inherited small vessel disease of the brain caused by mutations of the NOTCH3 gene encoding a receptor of smooth muscle cells and pericytes within the wall of arterioles and capillaries. The mutated gene is responsible for accumulation of NOTCH3 protein and aggregation of various proteins in the vascular wall. The disease occurs during mid-adulthood and is responsible for attacks of migraine with aura, ischemic stroke, mood disorders and cognitive impairment ranging from mild alterations of attentional performances and executive functions to severe dementia. The disease develops in adults with aging and is responsible at the latest stage of gait and balance troubles associated with cognitive impairment that may lead to severe disability and dependence. MRI shows widespread white matter lesions that may involve the anterior part of temporal lobes often associated with small cerebral infarcts and with microbleeds. The clinical severity is related to accumulation of small infarcts and the development of cerebral atrophy over time. The diagnosis of the disease is confirmed by genetic testing or skin biopsy.",Aged;CADASIL/diagnosis/genetics;Humans;Neuroimaging;Cadasil;Notch3;arteriolopathy;cerebral smallvessel disease;leukoencephalopathy,"Chabriat, H.",2014,Jun,,0,
5060,[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy],"CADASIL is an inherited small vessel disease of the brain caused by mutations of the NOTCH3 gene encoding a receptor of smooth muscle cells and pericytes within the wall of arterioles and capillaries. The mutated gene is responsible for accumulation of NOTCH3 protein and aggregation of various proteins in the vascular wall. The disease occurs during mid-adulthood and is responsible for attacks of migraine with aura, ischemic stroke, mood disorders and cognitive impairment ranging from mild alterations of attentional performances and executive functions to severe dementia. The disease develops in adults with aging and is responsible at the latest stage of gait and balance troubles associated with cognitive impairment that may lead to severe disability and dependence. MRI shows widespread white matter lesions that may involve the anterior part of temporal lobes often associated with small cerebral infarcts and with microbleeds. The clinical severity is related to accumulation of small infarcts and the development of cerebral atrophy over time. The diagnosis of the disease is confirmed by genetic testing or skin biopsy.",Aged;*CADASIL/diagnosis/genetics;Humans;Neuroimaging;Cadasil;Notch3;arteriolopathy;cerebral smallvessel disease;leukoencephalopathy,"Chabriat, H.",2014,Jun,10.1684/pnv.2014.0467,0,
5061,Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging,"Diffusion tensor imaging (DTI) can reveal detailed white matter anatomy and has the potential to detect abnormalities in specific white matter structures. Such detection and quantification are, however, not straightforward. The voxel-based analysis after image normalization is one of the most widely used methods for quantitative image analyses. To apply this approach to DTI, it is important to examine if structures in the white matter are well registered among subjects, which would be highly dependent on employed algorithms for normalization. In this paper, we evaluate the accuracy of normalization of DTI data using a highly elastic transformation algorithm, called large deformation diffeomorphic metric mapping. After simulation-based validation of the algorithm, DTI data from normal subjects were used to measure the registration accuracy. To examine the impact of morphological abnormalities on the accuracy, the algorithm was also tested using data from Alzheimer's disease (AD) patients with severe brain atrophy. The accuracy level was measured by using manual landmark-based white matter matching and surface-based brain and ventricle matching as gold standard. To improve the accuracy level, cascading and multi-contrast approaches were developed. The accuracy level for the white matter was 1.88+/-0.55 and 2.19+/-0.84 mm for the measured locations in the controls and patients, respectively.","Aged;Algorithms;Alzheimer Disease/ pathology;Artificial Intelligence;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Male;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity","Ceritoglu, C.;Oishi, K.;Li, X.;Chou, M. C.;Younes, L.;Albert, M.;Lyketsos, C.;van Zijl, P. C.;Miller, M. I.;Mori, S.",2009,Aug 15,10.1016/j.neuroimage.2009.04.057,0,
5062,Plasma homocysteine and severe white matter disease,"The objective of this study was to assess if high total plasma homocysteine (tHcy) levels are a risk factor for severe leukoaraiosis (LA). This case-control study was done in a primary care neurology ward and included 178 consecutive patients. Patients with severe LA at CT scan were compared with patients without any LA regarding age, cerebrovascular risk factors, tHcy, vitamin B12, folate, creatinine levels and dementia. Multivariate logistic regression was used to find variables independently associated with severe LA. Age (odds ratio [OR], 1.10 per year; p<0.0001), tHcy (OR, 1.07/μmol/l increase; p=0.045) and hypertension (OR, 2.97; p=0.007) were significantly associated with severe LA. Total homocysteine levels are associated with severe LA independently of other risk factors for cerebrovascular disease. This may suggest that decreasing tHcy may help preserve the integrity of the brain white matter. © Springer-Verlag Italia 2007.",creatinine;cyanocobalamin;folic acid;homocysteine;adult;age;aged;amino acid blood level;article;cerebrovascular accident;computer assisted tomography;controlled study;dementia;disease association;disease severity;female;human;hypertension;leukoaraiosis;major clinical study;male;risk assessment;risk factor;white matter,"Censori, B.;Partziguian, T.;Manara, O.;Poloni, M.",2007,,,0,
5063,Dementia after first stroke,"BACKGROUND AND PURPOSE: Cognitive deficits may significantly worsen the quality of life after stroke. Our aim was to determine the frequency of dementia in a consecutive series of previously nondemented patients between the ages of 40 and 79 years at 3 months after a first ischemic stroke. METHODS: All patients admitted to our department during an 18-month period who met the above criteria were visited and tested and underwent a CT scan 3 months after their stroke. Dementia was diagnosed according to criteria of the National Institute of Neurological Disorders and Stroke and AIREN, but cases with aphasia were not excluded. RESULTS: Of 304 patients admitted for stroke, 146 were eligible for study. Eleven refused to participate, 25 were dead at 3 months, and 110 were tested. Fifteen patients were demented (13.6%; 95% confidence interval [CI], 7.8% to 21.5%), and six had severe isolated aphasia, neglect, or memory deficit (5.4%). Excluding patients with aphasia, 5.0% of cases showed dementia (95% CI, 1.6% to 11.3%). The frequency of dementia was 24.6% (95% CI, 14.5% to 37.3%), considering only patients with supratentorial lesions and with residual deficits of elementary functions (paresis, sensory deficits) at the time of examination. Demented patients had significantly more diabetes (P<.029), atrial fibrillation (P=.032), aphasia at entry (P<.001), large middle cerebral artery infarctions (P=.001), and a more severe neurological deficit at entry (P=.003) and at 3 months (P=.001). At CT scan, demented patients had a larger mean volume of the recent lesion (P<.001) and more lesions in the frontal lobe (P=.041). An exploratory multivariate analysis selected age between 60 and 69 years (odds ratio [OR], 45.8; 95% CI, 2.9 to 726.0), diabetes (OR 59.4; 95% CI, 4.3 to 821.0), aphasia (OR, 14.8; 95% CI, 2.0 to 111.0), a large middle cerebral artery infarction (OR, 30.0; 95% CI, 2.7 to 334.0), and lesions of the frontal lobe (OR, 9.8; 95% CI, 1.3 to 72.8) as significant independent correlates of poststroke dementia. CONCLUSIONS: Dementia is relatively frequent after a clinical first stroke in persons younger than 80 years, and aphasia is very often associated with poststroke dementia. If aphasic patients are not considered, it may be necessary to screen a very large number of subjects to collect an adequate sample of demented cases.","Adult;Age Factors;Aged;Aphasia/etiology;Atrial Fibrillation/complications;Cerebral Arteries;Cerebral Infarction/complications;Cerebrovascular Disorders/*complications;Cognition Disorders/etiology;Dementia, Vascular/*etiology;Diabetes Complications;Female;Follow-Up Studies;Frontal Lobe/blood supply;Humans;Male;Memory Disorders/etiology;Middle Aged;Multivariate Analysis;Neurologic Examination;Paresis/etiology;Quality of Life;Sensation Disorders/etiology;Tomography, X-Ray Computed","Censori, B.;Manara, O.;Agostinis, C.;Camerlingo, M.;Casto, L.;Galavotti, B.;Partziguian, T.;Servalli, M. C.;Cesana, B.;Belloni, G.;Mamoli, A.",1996,Jul,,0,
5064,Association between ambulatory 24-hour blood pressure levels and brain volume reduction: a cross-sectional elderly population-based study,"Previous literature has shown mixed results regarding the association between blood pressure levels and brain volume reduction. The objectives of this study were to determine whether high blood pressure levels were associated with focal brain volume reduction and whether high blood pressure-related focal brain volume reduction was associated with a decline in executive function performance. On the basis of a cross-sectional design, 24-hour ambulatory blood pressure measurements, as well as brain morphology from 3-dimensional magnetic resonance images, were assessed among 183 participants (mean, 65 +/- 0.6 years; 62.4% women). Average levels of systolic and diastolic blood pressures, as well as dip, pulse pressure, and mean arterial blood pressure, were used as outcomes. Cortical gray and white matter volumes were determined by automatic calculation using Statistical Parametric Mapping segmentation. Folstein's Mini-Mental State Examination, digit span, part B of Trail Making, and Stroop tests were used to assess executive function performance. Sex, use of antihypertensive drugs, duration of hypertension, leukoaraiosis, body mass index, education level, and total brain matter volume were used as potential confounders. A significant blood pressure-related decrease in gray matter volume of the left supplementary motor areas (Brodmann area 6) and of the left superior and middle frontal gyrus (Brodmann area 8) was shown. No significant decrease was found with white matter volume. Blood pressure-related decreases in gray matter volume were significantly associated with a decline in executive function performance. The association of high blood pressure with brain volume reduction may in part explain blood pressure-related cognitive decline leading to dementia.","Aged;Antihypertensive Agents/therapeutic use;Blood Pressure/drug effects/ physiology;Blood Pressure Monitoring, Ambulatory/ methods;Brain/ pathology/physiopathology;Brain Mapping;Cognition/physiology;Cross-Sectional Studies;Female;Humans;Hypertension/drug therapy/physiopathology;Linear Models;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Multivariate Analysis;Population Surveillance/methods;Psychomotor Performance/physiology;Time Factors","Celle, S.;Annweiler, C.;Pichot, V.;Bartha, R.;Barthelemy, J. C.;Roche, F.;Beauchet, O.",2012,Nov,10.1161/hypertensionaha.112.193409,0,
5065,White matter involvement in sporadic Creutzfeldt-Jakob disease,"Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (P<0.05, corrected for multiple comparisons), with a generally symmetric pattern of involvement in sporadic Creutzfeldt-Jakob disease. Mean diffusivity reduction reflected concomitant decrease of both axial and radial diffusivity, without appreciable changes in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects. Neuropathological analysis showed diffuse astrocytic gliosis and activated microglia in the white matter, rare prion deposition and subtle subcortical microvacuolization, and patchy foci of demyelination with no evident white matter axonal degeneration. Decreased mean diffusivity on attenuation coefficient maps might be associated with astrocytic gliosis. We show for the first time significant global reduced mean diffusivity within the white matter in sporadic Creutzfeldt-Jakob disease, suggesting possible primary involvement of the white matter, rather than changes secondary to neuronal degeneration/loss.","Aged;Aged, 80 and over;Anisotropy;Creutzfeldt-Jakob Syndrome/ pathology;Demyelinating Diseases/pathology;Diffusion Magnetic Resonance Imaging/methods;Female;Gray Matter/pathology;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuroimaging;White Matter/ pathology","Caverzasi, E.;Mandelli, M. L.;DeArmond, S. J.;Hess, C. P.;Vitali, P.;Papinutto, N.;Oehler, A.;Miller, B. L.;Lobach, I. V.;Bastianello, S.;Geschwind, M. D.;Henry, R. G.",2014,Dec,10.1093/brain/awu298,0,
5066,Disrupted white matter structural networks in healthy older adult APOE epsilon4 carriers - An international multicenter DTI study,"The epsilon4 allelic variant of the Apolipoprotein E gene (APOE epsilon4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE epsilon4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals - 31 APOE epsilon4 carriers (APOE epsilon4+) and 43 APOE epsilon4 non-carriers (APOE epsilon4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE epsilon4+ and APOE epsilon4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE epsilon4+ compared to the APOE epsilon4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE epsilon4+, compared to APOE epsilon4- showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE varepsilon4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.",Apolipoprotein E;Diffusion Tensor Imaging;aging;multicenter study;white matter integrity,"Cavedo, E.;Lista, S.;Rojkova, K.;Chiesa, P. A.;Houot, M.;Brueggen, K.;Blautzik, J.;Bokde, A. L. W.;Dubois, B.;Barkhof, F.;Pouwels, P. J. W.;Teipel, S.;Hampel, H.;Alzheimer Precision Medicine, Initiative",2017,Aug 15,,0,
5067,Norms for imaging markers of brain reserve,"Brain reserve allows some people to be more resilient to neurodegeneration processes and brain diseases. Structural markers of brain reserve are hippocampus, lateral ventricles, and white matter lesions volume (HV, LVV, WMLV). Subjects in the low end of the distribution of these markers are at higher risk to develop brain diseases such as Alzheimer's disease. We described the distribution of the above markers in a large group of cognitively-intact persons. A sample of 158 people aged between 40 to 90 years (mean +/- SD: 60 +/- 12 years, education 9 +/- 4 years, MMSE score 28 +/- 2) belonging to the Italian Brain Normative Archive was selected. HV, LVV, and WMLV were measured with validated procedures. The HV and LVV were measured by manual segmentation and the Freesurfer software, respectively, and normalized by head size; WMLV was measured with semi-automated thresholding. Test-retest reliability was >0.83 for all measures. No relationship was found between HV and age, whereas a significant relationship was found for LVV and WMLV (ventricle left: B 0.02, 95% CI 0.22 to 0.34; ventricle right: B 0.02 95% CI 0.23 to 0.34 p < 0.001; WML: B 0.04; 95% CI 0.03 to 0.06 p < 0.005). The 5th percentile threshold indicating lower brain reserve were: (i) HV below 2,260 mm(3) at 40 and 2,000 mm(3) at 90; (ii) LVV above 17,000 mm(3) at 40 and 60,000 mm(3) at 90; and (iii) WMLV above 1,200 mm(3) at 40 and 8,700 mm(3) at 90. Normative data of brain reserve markers can be used to estimate the brain resilience to neurodegeneration.","Adult;Aged;Aged, 80 and over;Brain/ metabolism/physiology;Cognition/ physiology;Cognitive Reserve/ physiology;Female;Hippocampus/physiology;Humans;Lateral Ventricles/physiology;Magnetic Resonance Imaging/methods/ standards;Male;Middle Aged;Nerve Fibers, Myelinated/physiology;Neuropsychological Tests/standards;Organ Size","Cavedo, E.;Galluzzi, S.;Pievani, M.;Boccardi, M.;Frisoni, G. B.",2012,,10.3233/jad-2012-111817,0,
5068,Remote cerebellar haemorrhage after lumbar spine surgery: Case report,"Remote cerebellar haemorrhage (RCH) is a well-described complication of supratentorial surgical procedures with an incidence ranging between 0.2 and 4.9 %, but is a rare complication of spinal surgery. We report a case of RCH in a 65-year-old woman who showed sudden mental deterioration 48 h after lumbar spinal surgery, which was complicated by incidental dural tearing with minimal CSF loss. Brain CT scan revealed hypodense areas compatible with acute infarction involving mostly the left cerebellar hemisphere. No cerebral bleeding was observed. MRI was also performed revealing small cerebellar areas of acute infarction mainly relating the vermis and the left postero-inferior cerebellar hemisphere with haemorrhagic transformation and mass effect in the posterior fossa producing acute hydrocephalus. Haematoma removal was initially attempted by means of a suboccipital craniotomy. An external ventricular derivation was placed in a second procedure 24 h later due to the persistence of ventricular dilatation. At discharge the patient was only showing a slight dysmetria with the fine motor skills of hands and fingers. All cases of RCH after spinal surgery reported in the literature are invariably associated to iatrogenic dural tearing; although CSF loss seems to play the key role in the pathogenesis of this rare complication, the exact pathophysiology of this condition still remains undetermined. © 2013 Springer-Verlag Berlin Heidelberg.",aged;article;brain ventricle dilatation;case report;cerebellum hemorrhage;cerebellum infarction;cerebellum vermis;computer assisted tomography;craniotomy;dysmetria;female;hemisphere;human;hydrocephalus;liquorrhea;lumbar spine;mental deterioration;nuclear magnetic resonance imaging;postoperative period;priority journal;remote cerebellar hemorrhage;spinal cord decompression;spine surgery;vertebral canal stenosis,"Cavanilles-Walker, J. M.;Tomasi, S. O.;Sgier, F.;Kröber, M.",2013,,,0,
5069,Novel Method for Automated Analysis of Retinal Images: Results in Subjects with Hypertensive Retinopathy and CADASIL,"Morphological analysis of the retinal vessels by fundoscopy provides noninvasive means for detecting and staging systemic microvascular damage. However, full exploitation of fundoscopy in clinical settings is limited by paucity of quantitative, objective information obtainable through the observer-driven evaluations currently employed in routine practice. Here, we report on the development of a semiautomated, computer-based method to assess retinal vessel morphology. The method allows simultaneous and operator-independent quantitative assessment of arteriole-to-venule ratio, tortuosity index, and mean fractal dimension. The method was implemented in two conditions known for being associated with retinal vessel changes: hypertensive retinopathy and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). The results showed that our approach is effective in detecting and quantifying the retinal vessel abnormalities. Arteriole-to-venule ratio, tortuosity index, and mean fractal dimension were altered in the subjects with hypertensive retinopathy or CADASIL with respect to age- and gender-matched controls. The interrater reliability was excellent for all the three indices (intraclass correlation coefficient >/= 85%). The method represents simple and highly reproducible means for discriminating pathological conditions characterized by morphological changes of retinal vessels. The advantages of our method include simultaneous and operator-independent assessment of different parameters and improved reliability of the measurements.","Aged;Algorithms;CADASIL/ diagnosis/pathology;Diagnostic Techniques, Ophthalmological;Female;Humans;Hypertensive Retinopathy/ diagnosis/pathology;Image Interpretation, Computer-Assisted/ methods;Male;Middle Aged;Retina/ pathology;Retinal Vessels/pathology","Cavallari, M.;Stamile, C.;Umeton, R.;Calimeri, F.;Orzi, F.",2015,,10.1155/2015/752957,0,
5070,Brain atrophy and white-matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia,"Postoperative delirium is a common complication in older people and is associated with increased mortality, morbidity, institutionalization, and caregiver burden. Although delirium is an acute confusional state characterized by global impairments in attention and cognition, it has been implicated in permanent cognitive impairment and dementia. The pathogenesis of delirium and the mechanisms leading to these disabling consequences remain unclear. The present study is the first to address the potential predisposing role of brain morphologic changes toward postoperative delirium in a large prospective cohort of patients undergoing elective surgery using state-of-the-art magnetic resonance imaging (MRI) techniques conducted before admission. We investigated the association of MRI-derived quantitative measures of white-matter damage, global brain, and hippocampal volume with the incidence and severity of delirium. Presurgical white-matter hyperintensities (WMHs), whole brain, and hippocampal volume were measured in 146 consecutively enrolled subjects, >/=70 years old, without dementia who were undergoing elective surgery. These 3 presurgical MRI indices were tested as predictors of incidence and severity of subsequent delirium. Out of 146 subjects, 32 (22%) developed delirium. We found no statistically significant differences in WMH, whole brain, or hippocampal volume between subjects with and without delirium. Both unadjusted and adjusted (age, gender, vascular comorbidity, and general cognitive performance) regression analyses demonstrated no statistically significant association between any of the MRI measures with respect to delirium incidence or severity. In persons without dementia, preexisting cerebral WMHs, general and hippocampal atrophy may not predispose to postoperative delirium or worsen its severity.","Aged;Aged, 80 and over;Atrophy;Brain/ pathology;Delirium/ diagnosis/ epidemiology;Female;Hippocampus/pathology;Humans;Incidence;Magnetic Resonance Imaging;Male;Organ Size;Postoperative Complications/ epidemiology;Regression Analysis;Severity of Illness Index;White Matter/ pathology","Cavallari, M.;Hshieh, T. T.;Guttmann, C. R.;Ngo, L. H.;Meier, D. S.;Schmitt, E. M.;Marcantonio, E. R.;Jones, R. N.;Kosar, C. M.;Fong, T. G.;Press, D.;Inouye, S. K.;Alsop, D. C.",2015,Jun,10.1016/j.neurobiolaging.2015.02.024,0,
5071,Fractal analysis reveals reduced complexity of retinal vessels in CADASIL,"The Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) affects mainly small cerebral arteries and leads to disability and dementia. The relationship between clinical expression of the disease and progression of the microvessel pathology is, however, uncertain as we lack tools for imaging brain vessels in vivo. Ophthalmoscopy is regarded as a window into the cerebral microcirculation. In this study we carried out an ophthalmoscopic examination in subjects with CADASIL. Specifically, we performed fractal analysis of digital retinal photographs. Data are expressed as mean fractal dimension (mean-D), a parameter that reflects complexity of the retinal vessel branching. Ten subjects with genetically confirmed diagnosis of CADASIL and 10 sex and age-matched control subjects were enrolled. Fractal analysis of retinal digital images was performed by means of a computer-based program, and the data expressed as mean-D. Brain MRI lesion volume in FLAIR and T1-weighted images was assessed using MIPAV software. Paired t-test was used to disclose differences in mean-D between CADASIL and control groups. Spearman rank analysis was performed to evaluate potential associations between mean-D values and both disease duration and disease severity, the latter expressed as brain MRI lesion volumes, in the subjects with CADASIL. The results showed that mean-D value of patients (1.42+/-0.05; mean+/-SD) was lower than control (1.50+/-0.04; p = 0.002). Mean-D did not correlate with disease duration nor with MRI lesion volumes of the subjects with CADASIL. The findings suggest that fractal analysis is a sensitive tool to assess changes of retinal vessel branching, likely reflecting early brain microvessel alterations, in CADASIL patients.",Adult;CADASIL/ pathology;Case-Control Studies;Cohort Studies;Female;Fractals;Humans;Male;Middle Aged;Retinal Vessels/ pathology,"Cavallari, M.;Falco, T.;Frontali, M.;Romano, S.;Bagnato, F.;Orzi, F.",2011,,10.1371/journal.pone.0019150,0,
5072,Longitudinal diffusion changes following postoperative delirium in older people without dementia,"OBJECTIVE: To investigate the effect of postoperative delirium on longitudinal brain microstructural changes, as measured by diffusion tensor imaging. METHODS: We studied a subset of the larger Successful Aging after Elective Surgery (SAGES) study cohort of older adults (>/=70 years) without dementia undergoing elective surgery: 113 participants who had diffusion tensor imaging before and 1 year after surgery. Postoperative delirium severity and occurrence were assessed during the hospital stay using the Confusion Assessment Method and a validated chart review method. We investigated the association of delirium severity and occurrence with longitudinal diffusion changes across 1 year, adjusting for age, sex, vascular comorbidity, and baseline cognitive performance. We also assessed the association between changes in diffusion and cognitive performance across the 1-year follow-up period, adjusting for age, sex, education, and baseline cognitive performance. RESULTS: Postoperative delirium occurred in 25 participants (22%). Delirium severity and occurrence were associated with longitudinal diffusion changes in the periventricular, frontal, and temporal white matter. Diffusion changes were also associated with changes in cognitive performance across 1 year, although the cognitive changes did not show significant association with delirium severity or occurrence. CONCLUSIONS: Our study raises the possibility that delirium has an effect on the development of brain microstructural abnormalities, which may reflect brain changes underlying cognitive trajectories. Future studies are warranted to clarify whether delirium is the driving factor of the observed changes or rather a correlate of a vulnerable brain that is at high risk for neurodegenerative processes.",Aged;Brain/ diagnostic imaging;Delirium/ drug therapy/ etiology;Diffusion Tensor Imaging;Disease Progression;Elective Surgical Procedures;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Postoperative Complications/ diagnostic imaging;Prospective Studies;Severity of Illness Index,"Cavallari, M.;Dai, W.;Guttmann, C. R. G.;Meier, D. S.;Ngo, L. H.;Hshieh, T. T.;Fong, T. G.;Schmitt, E.;Press, D. Z.;Travison, T. G.;Marcantonio, E. R.;Jones, R. N.;Inouye, S. K.;Alsop, D. C.;Group, Sages Study",2017,Sep 5,,0,
5073,New development in diagnosis of vascular cognitive impairment,"Despite availability of harmonized criteria for the investigation of patients with presumed ""vascular cognitive impairment (VCI)"" there exists no clear definition of VCI. The challenge lies in the definition of those vascular components being responsible for the cognitive-behavioural decline of elderly patients. We advocate the use of longitudinal brain MRI studies to establish what type and extent of lesion progression parallels cognitive deterioration in elderly patients who often present with a plethora of diffuse and focal brain abnormalities that may or may not contribute to their cognitive phenotype. So far, a temporal relationship between lesion progression and cognitive decline has been established only for two types of ""vascular"" abnormalities. The most convincing evidence exists for confluent white matter lesions, less, but clearly supportive data are available for lacunes. All other brain abnormalities including microbleeds, loss of brain volume due to vascular processes or ultrastructural brain changes as seen with new imaging techniques need to be further explored in terms of their pathological correlates, rates of progression and their relationship to cognitive functioning. Such data are the pre-requisite to further develop the currently vague concept of VCI to a clearly defined diagnostic entity. © 2010 Elsevier B.V. All rights reserved.",,"Cavalieri, M.;Schmidt, R.",2010,15,,0,
5074,Structural MRI in normal aging and Alzheimer's disease: White and black spots,"Background: White matter changes (WMC) and microbleeds (MBs) are common in the elderly and in patients with Alzheimer's disease (AD). Objective: To describe the prevalence, anatomical distribution and longitudinal changes of WMC and MBs in normal aging subjects compared to AD patients and to describe current evidence of their effects on the clinical course of AD. Methods: Short literature review. Results: WMC and MBs are more frequent and progress more rapidly in AD patients than in cognitively normal elderly. New MBs occur in up to one quarter of AD cases without any therapeutic intervention. WMC and MBs influence the clinical course of AD. Conclusion: WMC and MBs might represent treatment targets in clinical trials on AD. Copyright © 2012 S. Karger AG, Basel.",aging;Alzheimer disease;article;brain disease;cognitive defect;comparative study;disease course;human;incidence;microbleed;mortality;nuclear magnetic resonance imaging;prevalence;priority journal;white matter change,"Cavalieri, M.;Schmidt, H.;Schmidt, R.",2012,,,0,
5075,"Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players","BACKGROUND: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. HYPOTHESIS: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. STUDY DESIGN: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. LEVEL OF EVIDENCE: Level 3. METHODS: Participants' histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. RESULTS: The retired players' ages averaged 45.6 +/- 8.9 years (range, 30-60 years), and they had 6.8 +/- 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 +/- 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central nervous system (CNS) neurological examinations. Four players (9%) had microbleeds in brain parenchyma identified in SWI, and 3 (7%) had a large cavum septum pellucidum with brain atrophy. The number of concussions/dings was associated with abnormal results in SWI and DTI. Neuropsychological testing revealed isolated impairments in 11 players (24%), but none had dementia. Nine players (20%) endorsed symptoms of moderate or severe depression on the BDI and/or met criteria for depression on PHQ; however, none had dementia, dysarthria, parkinsonism, or cerebellar dysfunction. The number of football-related concussions was associated with isolated abnormalities on the clinical neurological examination, suggesting CNS dysfunction. The APOE4 allele was present in 38% of the players, a larger number than would be expected in the general male population (23%-26%). CONCLUSION: MRI lesions and neuropsychological impairments were found in some players; however, the majority of retired NFL players had no clinical signs of chronic brain damage. CLINICAL RELEVANCE: These results need to be reconciled with the prevailing view that a career in football frequently results in chronic brain damage.",,"Casson, I. R.;Viano, D. C.;Haacke, E. M.;Kou, Z.;LeStrange, D. G.",2014,Sep,10.1177/1941738114540270,0,
5076,Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS,"The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates. © 2014 Caspers, Moebus, Lux, Pundt, Schütz, Mühleisen, Gras, Eickhoff, Romanzetti, Stöcker, Stirnberg, Kirlangic, Minnerop, Pieperhoff, Mödder, Das, Evans, Jöckel, Erbel, Cichon, Nöthen, Sturma, Bauer, Jon Shah, Zilles and Amunts.",,"Caspers, S.;Moebus, S.;Lux, S.;Pundt, N.;Schütz, H.;Mühleisen, T. W.;Gras, V.;Eickhoff, S. B.;Romanzetti, S.;Stöcker, T.;Stirnberg, R.;Kirlangic, M. E.;Minnerop, M.;Pieperhoff, P.;Mödder, U.;Das, S.;Evans, A. C.;Jöckel, K. H.;Erbel, R.;Cichon, S.;Nöthen, M. M.;Sturma, D.;Bauer, A.;Jon Shah, N.;Zilles, K.;Amunts, K.",2014,,,0,
5077,Cognitive impairment in progressive supranuclear palsy-Richardson's syndrome is related to white matter damage,"Introduction Beside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs. Methods We enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level. Results PSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from −0.80 to 0.74). Conclusions PSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs.",aged;article;brain dysfunction;brain size;cingulum (brain);clinical article;Clinical Dementia Rating;clinical examination;cognitive defect;controlled study;corpus callosum;cortical thickness (brain);diffusion tensor imaging;disease association;disease course;disease duration;female;frontal cortex;Hoehn and Yahr scale;human;male;mild cognitive impairment;Mini Mental State Examination;neuropsychological test;nuclear magnetic resonance imaging;occipital cortex;prediction;prefrontal cortex;priority journal;progressive supranuclear palsy;pyramidal tract;random forest;superior cerebellar peduncle;superior longitudinal fasciculus;temporal cortex;uncinate fasciculus;Unified Parkinson Disease Rating Scale;white matter injury,"Caso, F.;Agosta, F.;Volonté, M. A.;Ferraro, P. M.;Tiraboschi, P.;Copetti, M.;Valsasina, P.;Falautano, M.;Comi, G.;Falini, A.;Filippi, M.",2016,,10.1016/j.parkreldis.2016.07.007,0,
5078,White Matter Degeneration in Atypical Alzheimer Disease,"PURPOSE: To assess white matter (WM) tract damage in patients with atypical Alzheimer disease (AD), including early-onset AD (EOAD), logopenic variant of primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA), by using diffusion-tensor magnetic resonance (MR) imaging and to identify similarities and differences across the AD spectrum. MATERIALS AND METHODS: This study was approved by the local ethical committees on human studies, and written informed consent from all subjects was obtained prior to enrollment. WM tract damage and cortical atrophy were assessed by using diffusion-tensor MR imaging and voxel-based morphometry, respectively, in 28 patients with EOAD, 12 patients with lvPPA, and 13 patients with PCA relative to age- and sex-matched healthy subjects. Conjunction and interaction analyses were used to define overlapping and syndrome-specific patterns of brain damage. RESULTS: Patients with EOAD, lvPPA, and PCA shared a common pattern of WM damage that involved the body of the corpus callosum, fornix, and main anterior-posterior pathways (P < .05). They also shared cortical atrophy of the left temporoparietal regions and precuneus (P < .05, family-wise error corrected). Patients with EOAD also had specific damage to the genu and splenium of the corpus callosum and parahippocampal tract bilaterally (P < .05). In all patients with AD, particularly in the two focal forms (lvPPA and PCA), WM damage was more severe and widely distributed than expected on the basis of cortical atrophy. CONCLUSION: In atypical AD clinical phenotypes, the distribution of WM damage exceeds cortical atrophy and may reflect the pathologic dissemination through structural connections from atrophic to unaffected cortical regions. WM degeneration may be an early marker of AD pathologic changes in EOAD and focal AD forms.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Aphasia, Primary Progressive/ pathology;Atrophy;Cerebral Cortex/ pathology;Cross-Sectional Studies;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;White Matter/ pathology","Caso, F.;Agosta, F.;Mattavelli, D.;Migliaccio, R.;Canu, E.;Magnani, G.;Marcone, A.;Copetti, M.;Falautano, M.;Comi, G.;Falini, A.;Filippi, M.",2015,Oct,10.1148/radiol.2015142766,0,
5079,Clinical and MRI correlates of disease progression in a case of nonfluent/agrammatic variant of primary progressive aphasia due to progranulin (GRN) Cys157LysfsX97 mutation,"Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN +). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN + patient and this report offers new insights into the pathophysiology of the disease. © 2014 Elsevier B.V. All rights reserved.",progranulin;adult;agrammatism;apraxia of speech;article;ataxic aphasia;brain atrophy;brain damage;brain region;case report;clinical assessment;clinical evaluation;clinical feature;comprehension;controlled study;dementia;diffusion tensor imaging;disease course;family history;female;gene mutation;gray matter;human;language disability;medical history;morphometrics;nonfluent agrammatic variant primary progressive aphasia;nuclear magnetic resonance imaging;primary progressive aphasia;priority journal;speech disorder;tensor based morphometry;voxel based morphometry;white matter,"Caso, F.;Agosta, F.;Magnani, G.;Galantucci, S.;Spinelli, E. G.;Galimberti, D.;Falini, A.;Comi, G.;Filippi, M.",2014,,,0,
5080,Insights into White Matter Damage in Alzheimer's Disease: From Postmortem to in vivo Diffusion Tensor MRI Studies,"BACKGROUND: Alzheimer's disease (AD) has traditionally been considered a disease of the gray matter (GM). However, several pathological and neuroimaging studies provided evidence of white matter (WM) abnormalities in this disease. The advent of diffusion tensor (DT) MRI allowed researchers to study in vivo cerebral WM abnormalities in AD, including the earliest stage of the disease and its atypical variants. OBJECTIVE: To provide a concise overview of the main neuropathological and DT MRI studies that explored WM damage in AD providing new insights into the underlying pathophysiological mechanisms. RESULTS: Neuropathological studies revealed that GM and WM changes did not concur regionally in many areas, where well-preserved GM often lay over severely changed WM also in nondemented subjects with an underlying AD pathology. DT MRI studies confirmed in vivo a severe WM involvement in classical and atypical AD variants and in the prodromal stage of the disease. Microstructural WM damage was severer and more distributed than expected on the basis of cortical atrophy in all clinical AD phenotypes. CONCLUSIONS: AD is characterized by a relevant involvement of the WM as demonstrated by postmortem and in vivo evidence. WM microstructural damage in AD is not always secondary to neuronal loss, suggesting a role of other pathological mechanisms such as prion-like propagation of altered proteins or neuroinflammation. DT MRI offers new insight into AD pathophysiology and, more importantly, new possible targets for future experimental therapies.",,"Caso, F.;Agosta, F.;Filippi, M.",2016,,10.1159/000441422,0,
5081,The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study,"OBJECTIVE: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. METHODS: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxel-based morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. RESULTS: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. CONCLUSIONS: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.",Adult;Age of Onset;Alzheimer Disease/*genetics/*pathology;Atrophy/genetics;Cerebral Cortex/pathology;Cerebrum/*pathology;Cohort Studies;Female;Heterozygote;Humans;Magnetic Resonance Imaging/instrumentation/*methods;Male;Middle Aged;Prodromal Symptoms;Prognosis;Young Adult,"Cash, D. M.;Ridgway, G. R.;Liang, Y.;Ryan, N. S.;Kinnunen, K. M.;Yeatman, T.;Malone, I. B.;Benzinger, T. L.;Jack, C. R., Jr.;Thompson, P. M.;Ghetti, B. F.;Saykin, A. J.;Masters, C. L.;Ringman, J. M.;Salloway, S. P.;Schofield, P. R.;Sperling, R. A.;Cairns, N. J.;Marcus, D. S.;Xiong, C.;Bateman, R. J.;Morris, J. C.;Rossor, M. N.;Ourselin, S.;Fox, N. C.",2013,Oct 15,10.1212/WNL.0b013e3182a841c6,0,
5082,Cortical folding analysis on patients with Alzheimer's disease and mild cognitive impairment,"Cortical thinning is a widely used and powerful biomarker for measuring disease progression in Alzheimer's disease (AD). However, there has been little work on the effect of atrophy on the cortical folding patterns. In this study, we examined whether the cortical folding could be used as a biomarker of AD. Cortical folding metrics were computed on 678 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. For each subject, the boundary between grey matter and white matter was extracted using a level set technique. At each point on the boundary two metrics characterising folding, curvedness and shape index, were generated. Joint histograms using these metrics were calculated for five regions of interest (ROIs): frontal, temporal, occipital, and parietal lobes as well as the cingulum. Pixelwise statistical maps were generated from the joint histograms using permutations tests. In each ROI, a significant reduction was observed between controls and AD in areas associated with the sulcal folds, suggesting a sulcal opening associated with neurodegeneration. When comparing to MCI patients, the regions of significance were smaller but overlapping with those regions found comparing controls to AD. It indicates that the differences in cortical folding are progressive and can be detected before formal diagnosis of AD. Our preliminary analysis showed a viable signal in the cortical folding patterns for Alzheimer's disease that should be explored further.","*Algorithms;Alzheimer Disease/*complications/*pathology;Cerebral Cortex/*pathology;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/*methods;Magnetic Resonance Imaging/*methods;Mild Cognitive Impairment/*etiology/*pathology;Pattern Recognition, Automated/*methods;Reproducibility of Results;Sensitivity and Specificity","Cash, D. M.;Melbourne, A.;Modat, M.;Cardoso, M. J.;Clarkson, M. J.;Fox, N. C.;Ourselin, S.",2012,,,0,
5083,Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions,"BACKGROUND AND PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is typically characterized by headache, altered mental functioning, seizures, and visual loss associated with imaging findings of bilateral subcortical and cortical edema with a predominantly posterior distribution. Our goal was to determine whether fluid-attenuated inversion recovery (FLAIR) imaging improves the ability to detect subtle peripheral lesions of PRES, as compared with conventional MR techniques. METHODS: Sixteen patients with clinical and imaging findings consistent with PRES were studied. Thirteen patients had undergone transplantation and had cyclosporin A neurotoxicity. Fast-FLAIR images were compared with spin-echo proton density- and T2-weighted images. RESULTS: FLAIR imaging improved diagnostic confidence and conspicuity of the T2 hyperintense lesions of PRES, typically in the subcortical white matter of the parietooccipital regions bilaterally. On all 23 abnormal MR studies, FLAIR was judged superior to proton density- and T2-weighted images for the detection of PRES in the supratentorial brain. In a mean of 6.7 of 23 studies, FLAIR findings prompted a raise in the grade of disease severity. FLAIR also showed cortical involvement in 94% of patients with PRES and in a mean of 46% of the total lesion burden. In four cases, subtle lesions were virtually undetectable without FLAIR. Brain stem or cerebellar disease was encountered in 56% of patients. CONCLUSION: FLAIR improves the ability to diagnose and detect subcortical and cortical lesions in PRES as compared with proton density- and T2-weighted spin-echo images. We therefore believe that FLAIR should be performed in patients with suspected PRES to allow more confident recognition of the often subtle imaging abnormalities.","Adolescent;Adult;Brain/pathology;Brain Diseases/ diagnosis/etiology;Brain Edema/ diagnosis/etiology;Cerebral Cortex/pathology;Child;Child, Preschool;Cyclosporine/adverse effects/therapeutic use;Dementia, Vascular/ diagnosis/etiology;Diagnosis, Differential;Female;Humans;Hypertensive Encephalopathy/diagnosis/etiology;Image Enhancement;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Neurotoxicity Syndromes/diagnosis/etiology","Casey, S. O.;Sampaio, R. C.;Michel, E.;Truwit, C. L.",2000,Aug,,0,
5084,Cerebral Amyloid Angiopathy Is Associated With Executive Dysfunction and Mild Cognitive Impairment,"BACKGROUND AND PURPOSE: Autopsy studies suggest that cerebral amyloid angiopathy (CAA) is associated with cognitive impairment and risk for dementia. We analyzed neuropsychological test data from a prospective cohort study of patients with CAA to identify the prevalence of cognitive impairment and its associations with brain magnetic resonance imaging features and the apolipoprotein E genotype. METHODS: Data were analyzed from 34 CAA, 16 Alzheimer's disease, 69 mild cognitive impairment, and 27 ischemic stroke participants. Neuropsychological test results were expressed as z scores in relation to normative data provided by the test manuals and then grouped into domains of memory, executive function, and processing speed. RESULTS: Mean test scores in CAA participants were significantly lower than norms for memory (-0.44+/-1.03; P=0.02), executive function (-1.14+/-1.07; P<0.001), and processing speed (-1.06+/-1.12; P<0.001). Twenty-seven CAA participants (79%) had mild cognitive impairment based on low cognitive performance accompanied by cognitive concerns. CAA participants had similarly low executive function scores as Alzheimer's disease, but relatively preserved memory. CAA participants' scores were lower than those of ischemic stroke controls for executive function and processing speed. Lower processing speed scores in CAA were associated with higher magnetic resonance imaging white matter hyperintensity volume. There were no associations with the apolipoprotein E epsilon4 allele. CONCLUSIONS: Mild cognitive impairment is very prevalent in CAA. The overall cognitive profile of CAA is more similar to that seen in vascular cognitive impairment rather than Alzheimer's disease. White matter ischemic lesions may underlie some of the impaired processing speed in CAA.",Alzheimer's disease;cerebral amyloid angiopathy;cognitive impairment;intracerebral hemorrhage;magnetic resonance imaging,"Case, N. F.;Charlton, A.;Zwiers, A.;Batool, S.;McCreary, C. R.;Hogan, D. B.;Ismail, Z.;Zerna, C.;Coutts, S. B.;Frayne, R.;Goodyear, B.;Haffenden, A.;Smith, E. E.",2016,Aug,10.1161/strokeaha.116.012999,0,
5085,High dimensional classification of structural MRI Alzheimer's disease data based on large scale regularization,"In this work we use a large scale regularization approach based on penalized logistic regression to automatically classify structural MRI images (sMRI) according to cognitive status. Its performance is illustrated using sMRI data from the Alzheimer Disease Neuroimaging Initiative (ADNI) clinical database. We downloaded sMRI data from 98 subjects (49 cognitive normal and 49 patients) matched by age and sex from the ADNI website. Images were segmented and normalized using SPM8 and ANTS software packages. Classification was performed using GLMNET library implementation of penalized logistic regression based on coordinate-wise descent optimization techniques. To avoid optimistic estimates classification accuracy, sensitivity, and specificity were determined based on a combination of three-way split of the data with nested 10-fold cross-validations. One of the main features of this approach is that classification is performed based on large scale regularization. The methodology presented here was highly accurate, sensitive, and specific when automatically classifying sMRI images of cognitive normal subjects and Alzheimer disease (AD) patients. Higher levels of accuracy, sensitivity, and specificity were achieved for gray matter (GM) volume maps (85.7, 82.9, and 90%, respectively) compared to white matter volume maps (81.1, 80.6, and 82.5%, respectively). We found that GM and white matter tissues carry useful information for discriminating patients from cognitive normal subjects using sMRI brain data. Although we have demonstrated the efficacy of this voxel-wise classification method in discriminating cognitive normal subjects from AD patients, in principle it could be applied to any clinical population.",,"Casanova, R.;Whitlow, C. T.;Wagner, B.;Williamson, J.;Shumaker, S. A.;Maldjian, J. A.;Espeland, M. A.",2011,,10.3389/fninf.2011.00022,0,
5086,Changes in Gray-/White-Matter Ratios in the Parahippocampal Gyri of Late-Onset Schizophrenia Patients,"Objective: Recent neuropathological studies have reported that late-onset schizophrenia patients exhibit a restricted limbic tauopathy, glial tangles (thorn-shaped astrocytes), scarce amyloid deposition, and preservation of hippocampal pyramidal cells. The present article is an attempt at finding a macroscopic correlate to the described pathology. Methods: A group of 13 normal-onset (<40 years) schizopbrenic patients, 13 late-onset (>40 years) schizophrenia patients, and 8 comparison clients were studied, based on fulfillment of diagnostic criteria (e.g., DSM-III) and availability of suitable tissue. A computerized image analysis provided areal measurements of the hippocampal formation. Both hemispheres and two levels (mammillary bodies and lateral geniculate nucleus) were studied. In order to avoid corrections based on tissue shrinkage, results were expressed as ratios (e.g., parahippocampal gray/white matter). Results: Late-onset schizophrenic patients exhibit significant alterations in the gray-/white-matter ratio of the parahippocampal gyrus, affecting both hemispheres and all levels examined. This finding can best be explained by the preservation of gray matter and concomitant reduction of white matter in affected parahippocampal gyri. Conclusion: The presence of neuritic changes, preservation of pyramidal cell numbers, and of areal diminution of the parahippocampal white matter can best be explained by a dying-back neuropathy.",,"Casanova, M. F.;Lindzen, E. C.",2003,November/December,,0,
5087,Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease,"BACKGROUND AND PURPOSE: The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. MATERIALS AND METHODS: Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. RESULTS: Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. CONCLUSIONS: Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/metabolism/pathology/radionuclide imaging;Brain/metabolism/pathology/radionuclide imaging;Diffusion Tensor Imaging/ methods;Female;Fluorodeoxyglucose F18;Humans;Male;Middle Aged;Mild Cognitive Impairment/metabolism/pathology/radionuclide imaging;Multimodal Imaging/methods;Nerve Net/metabolism/pathology/radionuclide imaging;Neuropsychological Tests;Positron-Emission Tomography/ methods;Radiopharmaceuticals","Carter, S. F.;Embleton, K. V.;Anton-Rodriguez, J. M.;Burns, A.;Ralph, M. A.;Herholz, K.",2014,Jun,10.3174/ajnr.A3895,0,
5088,Selective cerebral volume reduction in Rett syndrome: A multiple-approach MR imaging study,"BACKGROUND AND PURPOSE: Previous studies have examined volumetric abnormalities in Rett syndrome (RTT), using MR imaging and focusing on selective changes. However, these studies preceded the identification of MECP2 as the gene mutated in most RTT cases. We studied regional brain volume changes as noted by MR imaging in girls with RTT who had mutations in the MECP2 gene and more or less severe clinical outcomes to further characterize the neuroanatomy of RTT and its correlations with clinical severity. MATERIALS AND METHODS: Complementary semiautomated Talairach- and voxel-based approaches were used to study spoiled gradient-recalled acquisition sequence MR imaging scans from 23 girls with MECP2 mutations/RTT, including a pair of discordant monozygotic twins and 25 age-matched control girls. Both absolute and relative volumetric changes were examined to account for the well-documented global reduction in brain volume seen in RTT. RESULTS: Absolute volumetric reductions were observed throughout the brain in RTT. Selective/relative decreases in parietal lobe gray matter, particularly in the dorsal parietal region, and mild, diffuse reductions in cortical white matter were observed in the RTT group compared with control subjects. In girls with RTT and a more severe phenotype, anterior frontal lobe volumes were relatively more reduced. Twin comparisons revealed selective preservation of the occipital cortex. CONCLUSION: Selective reductions of dorsal parietal gray matter and preservation of the occipital cortex seem to be basic neuroanatomy features of RTT, whereas preferential reduction of the anterior frontal lobe appears to be a correlate of clinical severity in this disorder. The most affected brain regions include those that may underlie key functional deficits observed in RTT.",,"Carter, J. C.;Lanham, D. C.;Pham, D.;Bibat, G.;Naidu, S.;Kaufmann, W. E.",2008,March,,0,
5089,Natural history of disease in the YAC128 mouse reveals a discrete signature of pathology in Huntington disease,"Models of Huntington disease (HD) recapitulate some neuropathological features of the disease. However, a global natural history of neuroanatomy in a mouse expressing full-length huntingtin has not been conducted. We investigated neuropathological changes in the YAC128 murine model of HD using magnetic resonance imaging (MRI). Structures affected in human HD are reduced in the YAC128 mice both in absolute terms and in terms of percentage of brain volume. Structures resistant to degeneration in HD, including the cerebellum and hippocampus, are spared in the YAC128 mice. Segmentation of major white matter structures confirms specific, progressive, loss of white matter in HD. In parallel with their specific volume loss, the YAC128 mice also show progressive increases in total ventricular volume, similarly to human HD patients. Cortical atrophy in the YAC128 mice is layer specific, which is the observed pattern of cortical loss in human HD patients. Finally, we have used a classification tree analysis to maximize separation of genotypes using all 62 structure volumes in an objective manner. This analysis demonstrates that sub-cortical gray matter structures (striatum, globus pallidus, thalamus) and cerebral white matter structures (corpus callosum, anterior commisure, fimbria) are the most discriminatory. The high resolution of the current study enables robust measurement of subtle early pathological changes. The use of mice furthermore enables us to address questions difficult to address in humans, including the sequential changes of HD from baseline and the relation between MRI and stereological measures.","Animals;Atrophy;Brain/metabolism/pathology;Cerebellum/metabolism/pathology;Disease Models, Animal;Disease Progression;Gene Expression Regulation/genetics;Humans;Huntington Disease/etiology/ genetics/ pathology;Magnetic Resonance Imaging/methods;Mice;Mice, Transgenic;Nerve Tissue Proteins/biosynthesis/ genetics;Nuclear Proteins/biosynthesis/ genetics","Carroll, J. B.;Lerch, J. P.;Franciosi, S.;Spreeuw, A.;Bissada, N.;Henkelman, R. M.;Hayden, M. R.",2011,Jul,10.1016/j.nbd.2011.03.018,0,
5090,Isolated lacunar infarct: An early clinical presentation of CADASIL?,,Notch3 receptor;adult;allodynia;CADASIL;case report;clinical examination;diffusion weighted imaging;exon;female;gene mutation;genetic screening;gestational age;hemiparesis;human;hypertension;lacunar stroke;medical history;migraine without aura;neuroimaging;nuclear magnetic resonance imaging;priority journal;short survey;tendon reflex;transesophageal echocardiography,"Carra-Dallière, C.;Ayrignac, X.;Renard, D.;Menjot De Champfleur, N.;Tourniaire, P.;Mine, M.;Labauge, P.",2013,,,0,
5091,Late and early onset dementia: what is the role of vascular factors? A retrospective study,"BACKGROUND: Neuropathology of Alzheimer's disease (AD) demonstrates that the common occurrence of vascular lesions and vascular factors is suggested to contribute significantly to the clinical progression of the disease. This study has assessed the presence of vascular brain lesions and risk factors in subjects with diagnosis of AD and their influence on the disease course both in Late Onset Dementia (LOD) and in Early Onset Dementia (EOD). METHODS: MRI scans of 374 LOD and of 67 EOD patients were evaluated for the presence of vascular associated lesions and rated according to the age-related white matter changes (ARWMC) scale as ""pure degenerative"", ""mixed"" and ""vascular"" cases of dementia. Vascular risk factors burden (hypertension, diabetes, dyslipidemia, myocardial infarction) and disease progression were also assessed. RESULTS: 44% of LOD cases and 46% of EOD were classified as ""mixed dementia cases"". The vascular risk factors burden showed an increase from the pure degenerative to the pure vascular forms. Disease progression, calculated in two years using the Mini Mental State Evaluation (MMSE), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scores, did not reveal differences among the three different classes of dementias. CONCLUSIONS: Vascular lesions are found in the majority of LOD cases and in about one half of EOD. This observation is consistent with the hypothesis of a synergistic effect of the degenerative and vascular factors on the development of cognitive dysfunction. The linear increase of the vascular burden supports the idea of a continuum spectrum between the pure degenerative and the pure vascular forms of adult-onset dementia disorders.","Activities of Daily Living;Age of Onset;Aged;Aged, 80 and over;Analysis of Variance;Brain/*pathology;Cerebrovascular Disorders/diagnosis/*epidemiology;Dementia/classification/*diagnosis/*epidemiology/psychology;Disease Progression;Female;Humans;Male;Mental Status Schedule;Retrospective Studies;Risk Factors;Time Factors","Carotenuto, A.;Rea, R.;Colucci, L.;Ziello, A. R.;Molino, I.;Carpi, S.;Traini, E.;Amenta, F.;Fasanaro, A. M.",2012,Nov 15,10.1016/j.jns.2012.07.066,0,
5092,Extensive white matter involvement in patients with frontotemporal lobar degeneration: Think progranulin,"IMPORTANCE: Mutations in the progranulin (GRN) gene are responsible for 20% of familial cases of frontotemporal dementias. All cause haploinsufficiency of progranulin, a protein involved in inflammation, tissue repair, and cancer. Carriers of the GRN mutation are characterized by a variable degree of asymmetric brain atrophy, predominantly in the frontal, temporal, and parietal lobes.We describe 4 GRN mutation carriers with remarkable widespread white matter lesions (WML) associated with lobar atrophy shown on magnetic resonance imaging. OBSERVATIONS: Four GRN mutation carriers (age at onset, 56-65 years) presenting with severe WML were selected from 31 GRN mutation carriers who were followed up in our dementia centers. The WML were predominantly in the frontal and parietal lobes and were mostly confluent, affecting the periventricular subcortical white matter and U-fibers. In all patients, common vascular,metabolic, inflammatory, dysimmune, and mitochondrial disorders were excluded and none had severe vascular risk factors. CONCLUSIONS AND RELEVANCE: Our data suggest that white matter involvement may be linked to progranulin pathological processes in a subset of GRN mutation carriers. The plasma progranulin measurement, which is predictive of GRN mutations, and GRN sequencing should thus be included in investigations of patients with frontotemporal lobar degenerations who show unusual white matter hyperintensities and atrophy on magnetic resonance imaging.",,"Caroppo, P.;Le Ber, I.;Camuzat, A.;Clot, F.;Naccache, L.;Lamari, F.;De Septenville, A.;Bertrand, A.;Belliard, S.;Hannequin, D.;Colliot, O.;Brice, A.",2014,1,,0,
5093,Cerebrospinal Fluid Anti-Amyloid-Beta; Autoantibodies and Amyloid PET in Cerebral Amyloid Angiopathy-Related Inflammation,"We report a biomarker and genetic evaluation of four patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) treated with corticosteroids. Patients presented with focal symptomatology and cognitive impairment. MRI revealed cortical microbleeds and asymmetrical hyperintense white matter lesions (WML). Cerebrospinal fluid (CSF) biomarker analyses showed increased anti-Aβ autoantibodies, t-Tau, and p-Tau and decreasedAβ40 andAβ42. After treatment, focal symptomatology disappeared, andWMLand anti-Aβautoantibodies decreased. TheAPOEε4 allelewas overrepresented. Florbetapir-PET showed cortical deposition with lower retention in swollen areas. In the case of suspected CAA-ri, both CSF anti-Aβ autoantibodies levels and Florbetapir-PET could provide highly useful data to guide the correct diagnosis.",amyloid beta protein antibody;amyloid beta protein[1-40];amyloid beta protein[1-42];apolipoprotein E4;corticosteroid;tau protein;adult;aged;aphasia;article;brain atrophy;brain hemorrhage;bronchopneumonia;case report;cerebellum hemorrhage;cerebrospinal fluid analysis;cognitive defect;corticosteroid therapy;death;dementia;disease marker;dyslipidemia;electroencephalogram;encephalitis;female;follow up;human;hypertension;male;mild cognitive impairment;neuroimaging;nuclear magnetic resonance imaging;paresis;positron emission tomography;priority journal;protein expression;seizure;siderosis;stereotypy;symptomatology;treatment duration;vascular amyloidosis;visual hallucination;white matter lesion,"Carmona-Iragui, M.;Fernández-Arcos, A.;Alcolea, D.;Piazza, F.;Morenas-Rodriguez, E.;Antón-Aguirre, S.;Sala, I.;Clarimon, J.;Dols-Icardo, O.;Camacho, V.;Sampedro, F.;Munuera, J.;Nuñez-Marin, F.;Lleó, A.;Fortea, J.;Gómez-Ansón, B.;Blesa, R.",2015,,,0,
5094,Ventricular volume and dementia progression in the Cardiovascular Health Study,"Elevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.","Aged;Aged, 80 and over;Aging/*pathology;Cognition Disorders/*pathology;Cross-Sectional Studies;Dementia/*pathology;Disease Progression;Female;Follow-Up Studies;Humans;Lateral Ventricles/*pathology;Linear Models;Magnetic Resonance Imaging/methods;Male;Predictive Value of Tests;Prospective Studies;Retrospective Studies;Time Factors","Carmichael, O. T.;Kuller, L. H.;Lopez, O. L.;Thompson, P. M.;Dutton, R. A.;Lu, A.;Lee, S. E.;Lee, J. Y.;Aizenstein, H. J.;Meltzer, C. C.;Liu, Y.;Toga, A. W.;Becker, J. T.",2007,Mar,10.1016/j.neurobiolaging.2006.01.006,0,
5095,"Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia","Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.","Aged;Aged, 80 and over;Case-Control Studies;Cerebral Ventricles/ pathology;Cognition Disorders/ pathology;Dementia/ pathology;Disease Progression;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Risk Factors;Severity of Illness Index;Time Factors","Carmichael, O. T.;Kuller, L. H.;Lopez, O. L.;Thompson, P. M.;Dutton, R. A.;Lu, A.;Lee, S. E.;Lee, J. Y.;Aizenstein, H. J.;Meltzer, C. C.;Liu, Y.;Toga, A. W.;Becker, J. T.",2007,Jan-Mar,10.1097/WAD.0b013e318032d2b1,0,
5096,Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative,"OBJECTIVE: To evaluate relationships between magnetic resonance imaging (MRI)-based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. DESIGN: Convenience sample in a clinical trial design. SUBJECTS: A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. RESULTS: Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. CONCLUSIONS: White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Atrophy/pathology;Brain/ pathology/physiopathology;Cognition/ physiology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Organ Size;Regression Analysis","Carmichael, O.;Schwarz, C.;Drucker, D.;Fletcher, E.;Harvey, D.;Beckett, L.;Jack, C. R., Jr.;Weiner, M.;DeCarli, C.",2010,Nov,10.1001/archneurol.2010.284,0,
5097,The joint effect of apolipoprotein E ε4 and MRI findings on lower- extremity function and decline in cognitive function,"Background. Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E ε4 (ApoE-ε4) allele. The objective of this study was to investigate the joint effect of ApoE-ε4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function. Methods. Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower- extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline. Results. For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-ε4 allele on cognitive decline and lower- extremity function was often greater than that expected from the separate effects combined. Conclusions. We conclude that radiological findings in conjunction with ApoE-ε4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-ε4.",apolipoprotein E4;aged;article;brain scintiscanning;brain size;cerebrospinal fluid;cognitive defect;function test;gait;human;leg;major clinical study;male;nuclear magnetic resonance imaging;physical performance;priority journal;white matter,"Carmelli, D.;DeCarli, C.;Swan, G. E.;Kelly-Hayes, M.;Wolf, P. A.;Reed, T.;Guralnik, J. M.",2000,,,0,
5098,The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function,"BACKGROUND: Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function. METHODS: Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline. RESULTS: For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined. CONCLUSIONS: We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.","Aged;Aged, 80 and over;Algorithms;Alleles;Apolipoprotein E4;Apolipoproteins E/ genetics;Brain/ pathology;Cerebrospinal Fluid;Cognition/physiology;Cognition Disorders/ physiopathology;Cohort Studies;Data Interpretation, Statistical;Disabled Persons;Follow-Up Studies;Gait/physiology;Humans;Leg/ physiology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Memory/physiology;Neuropsychological Tests;Postural Balance/physiology;Psychomotor Performance/ physiology;Risk Factors","Carmelli, D.;DeCarli, C.;Swan, G. E.;Kelly-Hayes, M.;Wolf, P. A.;Reed, T.;Guralnik, J. M.",2000,Feb,,0,
5099,Structural covariance of superficial white matter in mild Alzheimer's disease compared to normal aging,"Introduction: Interindividual variations in regional structural properties covary across the brain, thus forming networks that change as a result of aging and accompanying neurological conditions. The alterations of superficial white matter (SWM) in Alzheimer's disease (AD) are of special interest, since they follow the AD-specific pattern characterized by the strongest neurodegeneration of the medial temporal lobe and association cortices. Methods: Here, we present an SWM network analysis in comparison with SWM topography based on the myelin content quantified with magnetization transfer ratio (MTR) for 39 areas in each hemisphere in 15 AD patients and 15 controls. The networks are represented by graphs, in which nodes correspond to the areas, and edges denote statistical associations between them. Results: In both groups, the networks were characterized by asymmetrically distributed edges (predominantly in the left hemisphere). The AD-related differences were also leftward. The edges lost due to AD tended to connect nodes in the temporal lobe to other lobes or nodes within or between the latter lobes. The newly gained edges were mostly confined to the temporal and paralimbic regions, which manifest demyelination of SWM already in mild AD. Conclusion: This pattern suggests that the AD pathological process coordinates SWM demyelination in the temporal and paralimbic regions, but not elsewhere. A comparison of the MTR maps with MTR-based networks shows that although, in general, the changes in network architecture in AD recapitulate the topography of (de)myelination, some aspects of structural covariance (including the interhemispheric asymmetry of networks) have no immediate reflection in the myelination pattern. The network model of superficial WM myelination in healthy subjects and in patients with Alzheimer's disease (AD) shows that (1) regional covariance is predominant in the left hemisphere in both groups; (2) AD pathology coordinates demyelination in the temporal and paralimbic regions; (3) demyelination of other regions in AD is accompanied by their decreased covariance. Myelination topography and the network model complementarily describe the AD process.",myelin;aged;Alzheimer disease;article;brain asymmetry;clinical article;controlled study;covariance;demyelination;female;frontal lobe;graph theoretical analysis;gray matter;hippocampus;human;left hemisphere;limbic cortex;magnetization transfer ratio;male;nerve cell network;nervous system parameters;neuroimaging;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;priority journal;Ranvier node;region of interest;right hemisphere;structure analysis;temporal lobe;topography;white matter,"Carmeli, C.;Fornari, E.;Jalili, M.;Meuli, R.;Knyazeva, M. G.",2014,,,0,
5100,Demyelination in Mild Cognitive Impairment Suggests Progression Path to Alzheimer's Disease,"The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment (MCI) - is manifested by phenotypes classified into exclusively memory (single-domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to-AD progression occurs through the sMCI-to-mMCI sequence as a result of the extension of initial pathological processes. To support this hypothesis, we assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21 mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial temporal lobe and posterior structures including white matter (WM: splenium, posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and lingual gyri). A disjunction analysis showed the spread of demyelination to prefrontal WM and insula GM in executive mMCI. Our findings suggest that demyelination starts in the structures affected by neurofibrillary pathology; its presence correlates with the clinical picture and indicates the method of MCI-to-AD progression. In vivo staging of preclinical AD can be developed in terms of WM/GM demyelination. © 2013 Carmeli et al.",age distribution;aged;Alzheimer disease;article;brain atrophy;brain region;clinical article;controlled study;corona radiata (brain);demyelination;disease classification;disease course;educational status;female;gray matter;hippocampus;human;human tissue;insula;lingual gyrus;male;mild cognitive impairment;neuropathology;nuclear magnetic resonance imaging;parahippocampal gyrus;pathological anatomy;phenotype;prefrontal cortex;temporal lobe;voxel based morphometry;white matter,"Carmeli, C.;Donati, A.;Antille, V.;Viceic, D.;Ghika, J.;von Gunten, A.;Clarke, S.;Meuli, R.;Frackowiak, R. S.;Knyazeva, M. G.",2013,,,0,
5101,Vitamin D levels in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),"Besides its well known function on bone metabolism, vitamin D role in cerebrovascular pathologies including cerebral small vessel disease has been confirmed by recent meta-analysis. In this study, we measured vitamin D levels in 56 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients (mean age 49.9) with no or minimal disability (modified Ranking Score, mRS </=2) and in 56 age, sex and seasonality matched healthy controls. History of ischemic events was recorded and cognitive functions were assessed using the Mini-Mental State Examination. White matter hyperintensities on brain T2-weighted magnetic resonance images were classified according to a modified Fazekas scale. Comparison of vitamin D levels between patients and controls showed significant lower values (p < 0.05) in no-to-mild CADASIL patients and a higher number of subjects with severe deficiency [25(OH)D <10 ng/ml]. Vitamin D levels did not correlate with vascular risk factors, clinical data or Fazekas score. The role of vitamin D is worth to be further explored in prospective studies.",Cadasil;Cerebral small vessel disease;Vascular dementia;Vascular risk factors;Vitamin D,"Carluccio, M. A.;Di Donato, I.;Pescini, F.;Battaglini, M.;Bianchi, S.;Valenti, R.;Nannucci, S.;Franci, B.;Stromillo, M. L.;De Stefano, N.;Inzitari, D.;Pantoni, L.;Nuti, R.;Federico, A.;Gonnelli, S.;Dotti, M. T.",2017,Jul,,0,
5102,Safety of solanezumab in the EXPEDITION-EXT study up to 2 years in a mild to moderate Alzheimer's disease population,"Background: Solanezumab, a humanized monoclonal antibody that binds to the mid-domain of soluble amyloid beta (Abeta) peptide was developed for the treatment of Alzheimer's disease (AD). EXPEDITION and EXPEDITION2 (the ""feeder studies"") were Phase 3, 18-month, placebo-controlled studies investigating solanezumab (400mg/4 weeks) in patients with mild-to-moderate AD. EXPEDITION-EXT is an extension study in patients who completed EXPEDITION or EXPEDITION2. Methods: In EXPEDITION- EXT, all patients receive solanezumab (400mg/4 weeks) intravenously, but patients and site personnel remain blinded to original treatment assignment in the feeder studies. Safety endpoints were summarized for patients assigned to placebo in the feeder studies (PBOF) and solanezumab in the feeder studies (SLZF); statistical comparisons were not conducted. The data cut for this safety analysis occurred after all patients had completed 2 years or had discontinued in EXPEDITION-EXT, but all available data were included in the analyses; therefore some patients have more than 2 years of follow-up. Results: A total of 1457 patients enrolled in EXPEDITION-EXT. This represents a total of 2879 person-years of exposure to solanezumab, with 70% of patients having at least 18 months' exposure, and maximum exposure of almost 3.5 years in EXPEDITION-EXT. Patients were age 54-93 years; 67% had mild AD (Mini-Mental Status Examination [MMSE] 20-26) and 33% had moderate AD (MMSE 16-19) at baseline in the feeder studies. Deaths, serious adverse events, discontinuations due to an adverse event, treatment-emergent adverse events, and categorical increases in amyloid-related imaging abnormality-hemosiderin deposition (ARIA-H) were evenly distributed across feeder study treatment groups. Four patients in the PBOF group and 3 patients in the SLZF group experienced ARIA-edema/effusion (ARIA-E) during EXPEDITIONEXT; however, ARIA-E was not clearly related to symptoms in any patient. Overall, cardiac disorders were observed in similar proportions across groups, but among ischemic-related events, myocardial infarction and arteriosclerosis coronary artery occurred with greater frequency in the PBOF or SLZF group, respectively (Table 1). Conclusions: These results are consistent with previous safety findings from the EXPEDITION studies, indicating that solanezumab is generally well tolerated. ARIA and cardiovascular events will continue to be evaluated in ongoing studies to further characterize these potential risks. (Table Presented).",safety;population;Alzheimer disease;human;patient;exposure;imaging;death;mental health;follow up;coronary artery;examination;heart infarction;personnel;arteriosclerosis;diseases;controlled study;risk;Mini Mental State Examination;solanezumab;amyloid;placebo;hemosiderin;peptide;monoclonal antibody,"Carlson, C. D.;Sethuraman, G.;Andersen, S. W.;Holdridge, K. C.;Hoog, S. L.;Hayduk, R.;Siemers, E. R.",2015,,,0,
5103,Rapidly progressive dementia caused by nonenhancing primary lymphoma of the central nervous system,"A 76-year-old woman had rapidly progressive dementia over 4 months. Proton density- and T2-weighted MR images of the head showed increased signal in the periventricular and subcortical white matter of both cerebral hemispheres and the brain stem. Enhancement was not seen after administration of contrast material. Because of the rapid progression of the dementia and increasing signal abnormalities within the cerebral white matter, the patient underwent a craniotomy with biopsies of the right frontal lobe. Pathologic specimens were positive for malignant large-cell lymphoma, B-cell phenotype. The MR appearance is atypical for primary lymphoma of the central nervous system.",,"Carlson, B. A.",1996,October,,0,
5104,Marchiafava-Bignami disease: A case studied with brain magnetic resonance and SPECT,"Objective: To show the correlation between brain magnetic resonance images (MRI) and single-photon-emission computed tomography (SPECT) in a patient with Marchiafava-Bignami (MB) disease. Background: MB disease is a rare disorder associated with chronic alcoholism. It is characterized by symmetric demyelination of corpus callosum (CC) and adyacent white matter. These lesions can be demonstrated both by computed tomography or/and MRI. Scarce information is available about MRI and SPECT according to the research done. Design/methods: A 79-year-old white man with a history of excessive alcohol consumption (predominantly wine) was admitted to our Institute. A decrease in his physical activity was evidenced in the two years prior to admission and in the last twelve months progressive dementia with hallucinations and severe apathy developed. On admission neurologic examination showed oculi pale optic discs, left ear hipoacusia, action tremor of upper limbs and proximal hyporreflexia with distal arreflexia of all four limbs was observed. Affectation of higher cortical functions was evident. Cerebrospinal fluid was normal and serologies for syphilis and HIV were negative. Both renal and hepatic functions were normal. Brain MRI and SPECT were performed. The patient died 70 days after diagnosis of MB disease. Results: MRI scans of the brain showed multiple hyperintense T2-weighted lesions in white matter and basal ganglia. Cortical atrophy, especially in the fronto-temporal areas, and a CC thickness reduction were also observed. Saggital view showed an irregular cavitation in the genu of the CC, hypointense and hyperintense on T1 and T2-weighted images respectively. The SPECT showed an abnormal low perfusion on both frontal lobes, left temporo-parietal lobes and right basal ganglia. Conclusion: The clinical features and MRI were consistent with the diagnosis of MB disease. MRI and SPECT studies showed the connection between the lesion in the CC and bilateral cortical degeneration of the frontal lobes; nevertheless other affected regions were also evidenced by the SPECT.",,"Cardozo Oliver, J.;Malagold, S.;Liberé, G.;Casas Parera, I.",2006,2006,,0,
5105,"Associations among vascular risk factors, carotid atherosclerosis, and cortical volume and thickness in older adults","BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether the Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness are associated with cortical volume and thickness. METHODS: Consecutive subjects participating in a prospective cohort study of aging and mild cognitive impairment enriched for vascular risk factors for atherosclerosis underwent structural MRI scans at 3-T and 4-T MRI at 3 sites. Freesurfer (Version 5.1) was used to obtain regional measures of neocortical volumes (mm3) and thickness (mm). Multiple linear regression was used to determine the association of Framingham Cardiovascular Risk Profile and carotid artery intima-media thickness with cortical volume and thickness. RESULTS: One hundred fifty-two subjects (82 men) were aged 78 (+/-7) years, 94 had a clinical dementia rating of 0, 58 had a clinical dementia rating of 0.5, and the mean Mini-Mental State Examination was 28+/-2. Framingham Cardiovascular Risk Profile score was inversely associated with total gray matter volume and parietal and temporal gray matter volume (adjusted P<0.04). Framingham Cardiovascular Risk Profile was inversely associated with parietal and total cerebral gray matter thickness (adjusted P<0.03). Carotid artery intima-media thickness was inversely associated with thickness of parietal gray matter only (adjusted P=0.04). Including history of myocardial infarction or stroke and radiological evidence of brain infarction, or apolipoprotein E genotype did not alter relationships with Framingham Cardiovascular Risk Profile or carotid artery intima-media thickness. CONCLUSIONS: Increased cardiovascular risk was associated with reduced gray matter volume and thickness in regions also affected by Alzheimer disease independent of infarcts and apolipoprotein E genotype. These results suggest a ""double hit"" toward developing dementia when someone with incipient Alzheimer disease also has high cardiovascular risk.","Aged;Aged, 80 and over;Cardiovascular Diseases/*complications/pathology;Carotid Artery Diseases/*complications/pathology;*Carotid Intima-Media Thickness;Cerebral Cortex/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors","Cardenas, V. A.;Reed, B.;Chao, L. L.;Chui, H.;Sanossian, N.;DeCarli, C. C.;Mack, W.;Kramer, J.;Hodis, H. N.;Yan, M.;Buonocore, M. H.;Carmichael, O.;Jagust, W. J.;Weiner, M. W.",2012,Nov,10.1161/strokeaha.112.659722,0,
5106,Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy,"Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV + ) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV- controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P<.05) greater rates of white matter volume loss than HIV- control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.","AIDS Dementia Complex/drug therapy/ etiology;Acquired Immunodeficiency Syndrome/ complications/drug therapy;Adult;Anti-Retroviral Agents/therapeutic use;Atrophy;Brain/drug effects/ pathology;Disease Progression;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Middle Aged;Neuropsychological Tests","Cardenas, V. A.;Meyerhoff, D. J.;Studholme, C.;Kornak, J.;Rothlind, J.;Lampiris, H.;Neuhaus, J.;Grant, R. M.;Chao, L. L.;Truran, D.;Weiner, M. W.",2009,Jul,10.1080/13550280902973960,0,
5107,Deformation-based morphometry reveals brain atrophy in frontotemporal dementia,"OBJECTIVE: To compare deformation-based maps of local anatomical size between subjects with frontotemporal dementia (FTD) and healthy subjects to identify regions of the brain involved in FTD. DESIGN: Structural magnetic resonance images were obtained from 22 subjects with FTD and 22 cognitively normal, age-matched controls. We applied deformation-based morphometry and compared anatomy between groups using an analysis of covariance model that included a categorical variable denoting group membership and covaried for head size. SETTING: University of California, San Francisco, Memory and Aging Center, and the San Francisco Veterans Affairs Medical Center. PATIENTS: Twenty-two subjects with FTD and 22 cognitively normal, age-matched controls. INTERVENTIONS: Neurological, neuropsychological, and functional evaluations and magnetic resonance imaging. MAIN OUTCOME MEASURE: Deformation maps of local anatomical size. RESULTS: Patients with FTD showed extensive, significant atrophy of the frontal lobes, affecting both gray matter and white matter. Atrophy of similar magnitude but less significance was observed in the anterior temporal lobes. The subcortical and midbrain regions, particularly the thalamus, pons, and superior and inferior colliculi, showed strongly significant atrophy of smaller magnitude. CONCLUSIONS: We confirmed frontal and anterior temporal gray matter atrophy in FTD. The observed white matter loss, thalamic involvement, and midbrain atrophy are consistent with pathological findings in late-stage FTD. Dysfunction of ventral-frontal-brainstem circuitry may underlie some of the unique clinical features of FTD.","Aged;Atrophy;Brain/ pathology;Cluster Analysis;Dementia/ diagnosis;Female;Frontal Lobe/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mesencephalon/pathology;Middle Aged;Temporal Lobe/pathology;Thalamus/pathology","Cardenas, V. A.;Boxer, A. L.;Chao, L. L.;Gorno-Tempini, M. L.;Miller, B. L.;Weiner, M. W.;Studholme, C.",2007,Jun,10.1001/archneur.64.6.873,0,
5108,Longitudinal multiple sclerosis lesion segmentation: Resource and challenge,"In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4.4 time-points, and test data of fourteen subjects with a mean of 4.4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website2 The Challenge Evaluation Website is: http://smart-stats-tools.org/lesion-challenge-2015 as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.",adult;algorithm;article;controlled study;human;image processing;image segmentation;Internet;multiple sclerosis;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;quantitative analysis;white matter lesion,"Carass, A.;Roy, S.;Jog, A.;Cuzzocreo, J. L.;Magrath, E.;Gherman, A.;Button, J.;Nguyen, J.;Prados, F.;Sudre, C. H.;Jorge Cardoso, M.;Cawley, N.;Ciccarelli, O.;Wheeler-Kingshott, C. A. M.;Ourselin, S.;Catanese, L.;Deshpande, H.;Maurel, P.;Commowick, O.;Barillot, C.;Tomas-Fernandez, X.;Warfield, S. K.;Vaidya, S.;Chunduru, A.;Muthuganapathy, R.;Krishnamurthi, G.;Jesson, A.;Arbel, T.;Maier, O.;Handels, H.;Iheme, L. O.;Unay, D.;Jain, S.;Sima, D. M.;Smeets, D.;Ghafoorian, M.;Platel, B.;Birenbaum, A.;Greenspan, H.;Bazin, P. L.;Calabresi, P. A.;Crainiceanu, C. M.;Ellingsen, L. M.;Reich, D. S.;Prince, J. L.;Pham, D. L.",2017,,10.1016/j.neuroimage.2016.12.064,0,
5109,Diagnosis and management of sporadic cerebral amyloid angiopathy,"We propose a synthesis of the literature on sporadic cerebral amyloid angiopathy (CAA). CAA is caused by vascular deposits of Aß-amyloid peptides leading to cerebral small vessel disease. Interest in CAA has been growing in the medical community due to population aging, the severity of its main complication i.e. spontaneous lobar hematoma, and the development of non-invasive diagnostic methods with susceptibility-weighted magnetic resonance imaging (MRI). CAA is associated with age and Alzheimer's disease (AD): cerebrovascular deposits of Aß peptides are present in nearly 60% of patients over 80 years of age and in over 80% of patients with AD. CAA is responsible for 12 to 15% of cerebral hematomas, with a characteristic lobar location and an annual recurrence risk of 10%. Susceptibility-weighted and gradient-echo MRI are used to make a diagnosis of probable CAA according to the Boston criteria that are based on the existence of lobar hemorrhage, lobar microbleeds, or superficial cortical siderosis. We discuss other clinical manifestations of CAA (amyloid spells and cognitive decline) as well as MRI manifestations (non-traumatic subarachnoid hemorrhage of the convexity, posterior predominant white matter hypersignals, micro-infarcts, and enlarged perivascular spaces of the centrum semi ovale). Prevention of lobar hematoma is mainly based on optimal control of blood pressure and cautious prescription of antithrombotic treatments. The inflammatory form of CAA is rare but curable condition.",amyloid beta protein;anticoagulant agent;aging;Alzheimer disease;blood pressure regulation;brain hematoma;brain infarction;diagnostic procedure;disease association;human;incidence;nuclear magnetic resonance imaging;prescription;recurrence risk;short survey;subarachnoid hemorrhage;susceptibility weighted imaging;treatment indication;vascular amyloidosis;white matter lesion,"Capron, J.",2016,,10.1016/j.praneu.2016.10.001,0,
5110,Leukoaraiosis on magnetic resonance imaging correlates with worse outcomes after spontaneous intracerebral hemorrhage,"BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is associated with dementia, ischemic stroke, and intracerebral hemorrhage (ICH), but there are few data on how LA might impact outcomes after acute ICH. We tested the hypothesis that the severity of LA on magnetic resonance imaging is related to worse functional outcomes after spontaneous ICH. METHODS: We prospectively identified patients with spontaneous acute ICH. LA was identified on magnetic resonance imaging and its severity was graded using the Fazekas method to include a score for the deep white matter and periventricular regions. Outcomes were obtained at 14 days, 28 days, and 3 months with the modified Rankin Scale (mRS; a validated scale from 0 [no symptoms] to 6 [dead]) and analyzed with multivariate logistic regression. RESULTS: Higher Fazekas total (periventricular plus deep white matter) score correlated with higher mRS score at 14 days (P=0.02) and 3 months (P=0.02). This relationship was driven by the periventricular score, for which higher score (more severe disease) correlated with higher National Institute of Health Stroke Scale at 14 days (P=0.03), and higher mRS score at 14 days (P<0.001), 28 days (P=0.004), and 3 months (P=0.005). A higher (more severe) Fazekas periventricular score was associated with dependence or death at 3 months (odds ratio, 1.8 per point; 95% confidence interval, 1.02-3.1; P=0.04) after correction for the ICH score. CONCLUSIONS: Increased LA is an independent predictor of worse functional outcomes in patients after spontaneous ICH. The pathophysiology associating LA with worse outcomes requires further study. These data may improve prognostication and selection for clinical trials.","Aged;Aged, 80 and over;Cerebral Hemorrhage/ diagnosis/ physiopathology;Female;Follow-Up Studies;Humans;Leukoaraiosis/ pathology/physiopathology;Logistic Models;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Predictive Value of Tests;Prognosis;Prospective Studies;Severity of Illness Index","Caprio, F. Z.;Maas, M. B.;Rosenberg, N. F.;Kosteva, A. R.;Bernstein, R. A.;Alberts, M. J.;Prabhakaran, S.;Naidech, A. M.",2013,Mar,10.1161/strokeaha.112.676890,0,
5111,Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy,"BACKGROUND AND PURPOSE: Subcortical ischemic vascular dementia is associated with cortical hypometabolism and hypoperfusion, and this reduced cortical metabolism or blood flow can be detected with functional imaging such as positron emission tomography. The aim of this study was to characterize, by means of MR imaging and 1H MR spectroscopy, the structural and metabolic brain changes that occur among patients with subcortical ischemic vascular dementia compared with those of elderly control volunteers and patients with Alzheimer's disease. METHODS: Patients with dementia and lacunes (n = 11), cognitive impairment and lacunes (n = 14), and dementia without lacunes (n = 18) and healthy age-matched control volunteers (n = 20) underwent MR imaging and 1H MR spectroscopy. 1H MR spectroscopy data were coanalyzed with coregistered segmented MR images to account for atrophy and tissue composition. RESULTS: Compared with healthy control volunteers, patients with dementia and lacunes had 11.74% lower N-acetylaspartate/creatine ratios (NAA/Cr) (P = .007) and 10.25% lower N-acetylaspartate measurements (NAA) in the cerebral cortex (P = .03). In white matter, patients with dementia and lacunes showed a 10.56% NAA/Cr reduction (P = .01) and a 12.64% NAA reduction (P = .04) compared with control subjects. NAA in the frontal cortex was negatively correlated with the volume of white matter signal hyperintensity among patients with cognitive impairment and lacunes (P = .002). Patients with dementia, but not patients with dementia and lacunes, showed a 10.33% NAA/Cr decrease (P = .02) in the hippocampus compared with healthy control volunteers. CONCLUSION: Patients with dementia and lacunes have reduced NAA and NAA/Cr in both cortical and white matter regions. Cortical changes may result from cortical ischemia/infarction, retrograde or trans-synaptic injury (or both) secondary to subcortical neuronal loss, or concurrent Alzheimer's pathologic abnormalities. Cortical derangement may contribute to dementia among patients with subcortical infarction.","Aged;Aspartic Acid/analogs & derivatives/metabolism;Brain Ischemia/complications/ diagnosis/ metabolism;Creatine/metabolism;Dementia, Vascular/complications/ diagnosis/ metabolism;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male","Capizzano, A. A.;Schuff, N.;Amend, D. L.;Tanabe, J. L.;Norman, D.;Maudsley, A. A.;Jagust, W.;Chui, H. C.;Fein, G.;Segal, M. R.;Weiner, M. W.",2000,Apr,,0,
5112,White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease,"Background and objective: Methodological variability in the assessment of white matter hyperintensities (WMH) in dementia may explain inconsistent reports of its prevalence and impact on cognition. We used a method of brain MRI segmentation for quantifying both tissue and WMH volumes in Alzheimer's disease (AD) and examined the association between WMH and structural and cognitive variables. Methods: A consecutive series of 81 patients meeting NINCDS-ADRDA criteria for probable AD was studied. Nineteen healthy volunteers of comparable age served as the control group. Patients had a complete neurological and neuropsychological evaluation, and a three dimensional MRI was obtained. Images were segmented into grey matter, white matter, and cerebrospinal fluid. WMH were edited on segmented images, and lobar assignments were based on Talairach coordinates. Results: Mild and moderate to severe AD patients had significantly more WMH than controls (p<0.05). WMH preferentially involved the frontal lobes (70%), were inversely correlated with grey matter cortical volume (R (2) = 0.23, p<0.001), and were significantly associated with vascular risk factors and with a worse performance on memory tasks. Conclusion: Objective measurements of tissue volumes in AD demonstrated that WMH are significantly related to cortical atrophy and neuropsychological impairment.",,"Capizzano, A. A.;Ación, L.;Bekinschtein, T.;Furman, M.;Gomila, H.;Martínes, A.;Mizrahi, R.;Starkstein, S. E.",2004,June,,0,
5113,The neuropsychological characteristics and regional cerebral blood flow of vascular cognitive impairment-no dementia,"OBJECTIVE: To investigate the neuropsychological characteristics of VCI-ND and to analyze the relationship between deficit pattern and regional cerebral blood flow (rCBF) in various VCI-ND subtypes defined by cognitive features. METHODS: 69 subjects diagnosed with VCI-ND were recruited, then further classified into four subtypes: amnestic VCI-ND with single memory impairment (subtype I, n = 19), amnestic VCI-ND with multi-domain impairment (subtype II, n = 27), non-amnestic VCI-ND with single domain impairment (subtype III, n = 16), and non-amnestic VCI-ND with multi-domain impairment (subtype IV, n = 7) according to their cognitive profile. Xenon-CT scan was administered to 31 VCI-ND patients (11 of subtype I, 12 of subtype II and 8 of subtype III) and 10 normal controls (NC) to evaluate rCBF. RESULTS: The rate of different cognitive domains impairment in VCI-ND group ranged from 17 to 66%, lowest in clock drawing test and highest in time of modified version of trails making test A and maze tracing compared with NC, significant reduced rCBF was found in bilateral temporal lobe and thalamus, left periventricular white matter and caudate of subtype I, and in left temporal lobe and lenticular nucleus, bilateral periventricular white matter, white matter adjacent to left posterior horn of lateral ventricular and right caudate of subtype III, while significant reduced rCBF of subtype II was found in left subfrontal white matter, bilateral subtemporoparietal white matter, right lenticular nucleus, and in both regions of subtype I and III. CONCLUSIONS: The manifestation of rCBF in VCI-ND subtypes was consistent with performance of neuropsychological assessment.","Aged;Brain/*blood supply;Cognition Disorders/*physiopathology/*psychology;Dementia, Vascular/*physiopathology/*psychology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Regional Blood Flow/physiology;Tomography, X-Ray Computed/methods;Xenon","Cao, X.;Guo, Q.;Zhao, Q.;Jin, L.;Fu, J.;Hong, Z.",2010,Nov,10.1002/gps.2458,0,
5114,Deep microbleeds and periventricular white matter disintegrity are independent predictors of attention/executive dysfunction in non-dementia patients with small vessel disease,"BACKGROUND: Cerebral small vessel disease (SVD) is the common cause of cognitive decline in the old population. MRI can be used to clarify its mechanisms. However, the surrogate markers of MRI for early cognitive impairment in SVD remain uncertain to date. We investigated the cognitive impacts of cerebral microbleeds (CMBs), diffusion tensor imaging (DTI), and brain volumetric measurements in a cohort of post-stroke non-dementia SVD patients. METHODS: Fifty five non-dementia SVD patients were consecutively recruited and categorized into two groups as no cognitive impairment (NCI) (n = 23) or vascular mild cognitive impairment (VaMCI) (n = 32). Detailed neuropsychological assessment and multimodal MRI were completed. RESULTS: The two groups differed significantly on Z scores of all cognitive domains (all p < 0.01) except for the language. There were more patients with hypertension (p = 0.038) or depression (p = 0.019) in the VaMCI than those in the NCI group. Multiple regression analysis of cognition showed periventricular mean diffusivity (MD) (beta = -0.457, p < 0.01) and deep CMBs numbers (beta = -0.352, p < 0.01) as the predictors of attention/executive function, which explained 45.2% of the total variance. Periventricular MD was the independent predictor for either memory (beta = -0.314, p < 0.05) or visuo-spatial function (beta = -0.375, p < 0.01); however, only small proportion of variance could be accounted for (9.8% and 12.4%, respectively). Language was not found to be correlated with any of the MRI parameters. No correlation was found between brain atrophic indices and any of the cognitive measures. CONCLUSION: Arteriosclerotic CMBs and periventricular white matter disintegrity seem to be independent MRI surrogated markers in the early stage of cognitive impairment in SVD.",cerebral microbleeds;diffusion tensor imaging;small vessel disease;vascular cognitive impairment;vascular mild cognitive impairment,"Cao, W. W.;Wang, Y.;Dong, Q.;Chen, X.;Li, Y. S.;Zhou, Y.;Gao, L.;Deng, Y.;Xu, Q.",2017,May,,0,
5115,Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment,"Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Abeta42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Abeta42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. SIGNIFICANCE STATEMENT: In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas.","Aged;Aged, 80 and over;Amyloid beta-Peptides/ cerebrospinal fluid;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Humans;Magnetocardiography;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/ cerebrospinal fluid/ pathology;Neuropsychological Tests;Peptide Fragments/ cerebrospinal fluid;tau Proteins/ cerebrospinal fluid","Canuet, L.;Pusil, S.;Lopez, M. E.;Bajo, R.;Pineda-Pardo, J. A.;Cuesta, P.;Galvez, G.;Gaztelu, J. M.;Lourido, D.;Garcia-Ribas, G.;Maestu, F.",2015,Jul 15,10.1523/jneurosci.0704-15.2015,0,
5116,Mapping the structural brain changes in Alzheimers Disease: The independent contribution of two imaging modalities,"The macrostructural atrophy of Alzheimers disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion-weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and viceversa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques. © 2011 IOS Press and the authors. All rights reserved.",aged;Alzheimer disease;article;brain atrophy;brain mapping;brain size;clinical article;controlled study;diffusion weighted imaging;female;fractional anisotropy;human;male;neuroimaging;neuropathology;nuclear magnetic resonance scanner;priority journal;ultrastructure;voxel based morphometry;Siemens Allegra,"Canu, E.;McLaren, D. G.;Fitzgerald, M. E.;Bendlin, B. B.;Zoccatelli, G.;Alessandrini, F.;Pizzini, F. B.;Ricciardi, G. K.;Beltramello, A.;Johnson, S. C.;Frisoni, G. B.",2011,,10.3233/jad-2011-0040,0,
5117,Microstructural diffusion changes are independent of macrostructural volume loss in moderate to severe Alzheimer's disease,"Although it is established that Alzheimer's disease (AD) leads to cerebral macrostructural atrophy, microstructural diffusion changes have also been observed, but it is not yet known whether these changes offer unique information about the disease pathology. Thus, a multi-modal imaging study was conducted to determine the independent contribution of each modality in moderate to severe AD. Seventeen patients with moderate-severe AD and 13 healthy volunteers underwent diffusion-weighted and T1-weighted MR scanning. Images were processed to obtain measures of macrostructural atrophy (gray and white matter volumes) and microstructural damage (fractional anisotropy and mean diffusivity). Microstructural diffusion changes independent of macrostructural loss were investigated using an ANCOVA where macrostructural maps were used as voxel-wise covariates. The reverse ANCOVA model was also assessed, where macrostructural loss was the dependent variable and microstructural diffusion tensor imaging maps were the imaging covariates. Diffusion differences between patients and controls were observed after controlling for volumetric differences in medial temporal, retrosplenial regions, anterior commissure, corona radiata, internal capsule, thalamus, corticopontine tracts, cerebral peduncle, striatum, and precentral gyrus. Independent volumetric differences were observed in the entorhinal cortex, inferior temporal lobe, posterior cingulate cortex, splenium and cerebellum. While it is well known that AD is associated with pronounced volumetric change, this study suggests that measures of microstructure provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD and in those thought to be spared. As such this work provides great understanding of the topography of pathological changes in AD that can be captured with imaging.","Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology;Anisotropy;Brain Mapping;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Image Processing, Computer-Assisted/ instrumentation;Male;Neuropsychological Tests;Severity of Illness Index","Canu, E.;McLaren, D. G.;Fitzgerald, M. E.;Bendlin, B. B.;Zoccatelli, G.;Alessandrini, F.;Pizzini, F. B.;Ricciardi, G. K.;Beltramello, A.;Johnson, S. C.;Frisoni, G. B.",2010,,10.3233/jad-2010-1295,0,
5118,Mapping the structural brain changes in Alzheimer's disease: The independent contribution of two imaging modalities,"The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion-weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and viceversa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques. © 2011 The authors and IOS Press. All rights reserved.",,"Canu, E.;McLaren, D. G.;Fitzgerald, M. E.;Bendlin, B. B.;Zoccatelli, G.;Alessandrini, F.;Pizzini, F. B.;Ricciardi, G. K.;Beltramello, A.;Johnson, S. C.",2011,2011,,0,
5119,Early and late onset Alzheimer's disease patients have distinct patterns of white matter damage,"We investigated patterns of white matter (WM) loss in 18 early onset (EO) and 24 late onset (LO) Alzheimer's disease (AD) patients compared with 42 healthy controls (HC), and explored relationships of WM atrophy and apolipoprotein E (ApoE) genotype. Subjects underwent magnetic resonance imaging (MRI). Patterns of WM were assessed using voxel-based morphometry. Compared with healthy controls, LOAD patients had a selective parahippocampal WM loss, while EOAD patients experienced a more widespread pattern of posterior WM atrophy. The distinct regional distribution of WM atrophy reflected the topography of gray matter (GM) loss. ApoE epsilon4 status was associated with a greater parahippocampal WM loss in both AD groups. The greater WM atrophy in EOAD than LOAD fits with the evidence that EOAD is a more aggressive form of the disease. The ApoE epsilon4 effect on WM damage in AD is restricted to specific WM regions and does not seem to be related to age of onset.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ pathology/psychology;Brain/ pathology;Cognition Disorders/epidemiology/pathology/psychology;Female;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Canu, E.;Frisoni, G. B.;Agosta, F.;Pievani, M.;Bonetti, M.;Filippi, M.",2012,Jun,10.1016/j.neurobiolaging.2010.09.021,0,
5120,White matter microstructural damage in Alzheimer's disease at different ages of onset,"White matter (WM) microstructural damage and its relationship with cortical abnormalities were explored in early-onset Alzheimer's disease (EOAD) compared with late-onset AD (LOAD) patients. Structural and diffusion tensor magnetic resonance images were obtained from 22 EOAD patients, 35 LOAD patients, and 40 healthy controls. Patterns of WM microstructural damage and cortical atrophy, as well as their relationships, were assessed using tract-based spatial statistics, tractography and voxel-based morphometry. Compared with LOAD, EOAD patients had a more severe and distributed pattern of WM microstructural damage, in particular in the posterior fibers of cingulum and corpus callosum. In both groups with Alzheimer's disease, but especially in LOAD patients, correlations between cingulum and corpus callosum fractional anisotropy and parietal, temporal, and frontal cortical volumes were found. In conclusion, WM microstructural damage is more severe in EOAD compared with LOAD patients. Such damage follows different patterns of topographical distribution in the 2 patient groups.","Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/epidemiology/ pathology;Brain Mapping;Cerebral Cortex/ pathology;Corpus Callosum/pathology;Diffusion Magnetic Resonance Imaging/methods;Diffusion Tensor Imaging;Female;Gyrus Cinguli/pathology;Humans;Male;Middle Aged;Severity of Illness Index","Canu, E.;Agosta, F.;Spinelli, E. G.;Magnani, G.;Marcone, A.;Scola, E.;Falautano, M.;Comi, G.;Falini, A.;Filippi, M.",2013,Oct,10.1016/j.neurobiolaging.2013.03.026,0,
5121,Multiparametric MRI to distinguish early onset Alzheimer's disease and behavioural variant of frontotemporal dementia,"This prospective study explored whether an approach combining structural [cortical thickness and white matter (WM) microstructure] and resting state functional MRI can aid differentiation between 62 early onset Alzheimer's disease (EOAD) and 27 behavioural variant of frontotemporal dementia (bvFTD) patients. Random forest and receiver operator characteristic curve analyses assessed the ability of MRI in classifying the two clinical syndromes. All patients showed a distributed pattern of brain alterations relative to controls. Compared to bvFTD, EOAD patients showed bilateral inferior parietal cortical thinning and decreased default mode network functional connectivity. Compared to EOAD, bvFTD patients showed bilateral orbitofrontal and temporal cortical thinning, and WM damage of the corpus callosum, bilateral uncinate fasciculus, and left superior longitudinal fasciculus. Random forest analysis revealed that left inferior parietal cortical thickness (accuracy 0.78, specificity 0.76, sensitivity 0.83) and WM integrity of the right uncinate fasciculus (accuracy 0.81, specificity 0.96, sensitivity 0.43) were the best predictors of clinical diagnosis. The combination of cortical thickness and DT MRI measures was able to distinguish patients with EOAD and bvFTD with accuracy 0.82, specificity 0.76, and sensitivity 0.96. The diagnostic ability of MRI models was confirmed in a subsample of patients with biomarker-based clinical diagnosis. Multiparametric MRI is useful to identify brain alterations which are specific to EOAD and bvFTD. A severe cortical involvement is suggestive of EOAD, while a prominent WM damage is indicative of bvFTD.","ACE-R, Addenbrooke's Cognitive Examination-revised;Behavioural variant of frontotemporal dementia;CC, corpus callosum;CSF, cerebrospinal fluid;Cortical thickness;DMN, default mode network;DT, diffusion tensor;Diagnosis;EOAD, early onset Alzheimer's disease;Early onset Alzheimer's disease;GM, grey matter;IC, independent component;ILF, inferior longitudinal fasciculus;LOAD, late onset Alzheimer's disease;MNI, Montreal Neurological Institute;NVI, Normalized Variable Importance;RS fMRI, resting state functional MRI;RSN, resting state network;Resting state functional MRI;SLF, superior longitudinal fasciculus;TFCE, threshold-free cluster enhancement;WM, white matter;White matter (WM) damage;bvFTD, behavioural variant frontotemporal dementia","Canu, E.;Agosta, F.;Mandic-Stojmenovic, G.;Stojkovic, T.;Stefanova, E.;Inuggi, A.;Imperiale, F.;Copetti, M.;Kostic, V. S.;Filippi, M.",2017,,,0,
5122,Cerebral changes and disrupted gray matter cortical networks in asymptomatic older adults at risk for Alzheimer's disease,"The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-beta (Abeta1-42(+)) (N = 19), and positive phosphorylated tau (N = 18). The Abeta1-42(+) group exhibited thickening of middle temporal regions, while positive phosphorylated tau individuals showed thinning in the superior parietal and orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed regional white matter atrophy and more segregated cortical networks, the Abeta1-42(+) group showing heightened isolation of cingulate and temporal cortices. Collectively, these findings highlight the relevance of combining structural brain imaging and connectomics for in vivo tracking of Alzheimer's disease lesions in asymptomatic stages.",CSF biomarkers;Cortical thickness;Preclinical Alzheimer's disease;Snap;Structural cortical networks;White matter,"Cantero, J. L.;Atienza, M.;Sanchez-Juan, P.;Rodriguez-Rodriguez, E.;Vazquez-Higuera, J. L.;Pozueta, A.;Gonzalez-Suarez, A.;Vilaplana, E.;Pegueroles, J.;Montal, V.;Blesa, R.;Alcolea, D.;Lleo, A.;Fortea, J.",2017,Dec 20,,0,
5123,Multiple brain calcifications in a patient with systemic lupus erythematosus,"We describe a rare case of severe neuropsychiatric systemic lupus erythematosus with cerebral atrophy and multiple paraventricular, basal ganglia, cortex, cerebral white matter, and cerebellum calcifications detected on cerebral CT. These calcifications are probably secondary to necrosis focus of repeated episodes of vessels inflammation. © Clinical Rheumatology 2008.",antinuclear antibody;autoantibody;azathioprine;cyclophosphamide;double stranded DNA antibody;immunoglobulin;immunosuppressive agent;ribonucleoprotein antibody;rituximab;Sm antibody;steroid;adult;alopecia;arthritis;article;brain atrophy;brain calcification;case report;cerebellum disease;clinical feature;computer assisted tomography;dementia;depression;disease association;drug megadose;Fahr disease;female;fever;health program;hematuria;hemolytic anemia;human;leukopenia;mouth ulcer;myalgia;neurogenic bladder;neurology;neuropsychology;physical medicine;plasmapheresis;priority journal;proteinuria;rash;seizure;spasticity;systemic lupus erythematosus;vasculitis;white matter,"Cañas, C. A.;Tobón, G. J.",2008,,,0,
5124,Impaired vasoreactivity in mildly disabled CADASIL patients,"BACKGROUND AND PURPOSE: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare genetic disease caused by NOTCH3 gene mutations. A dysfunction in vasoreactivity has been proposed as an early event in the pathogenesis of the disease. The aim of this study was to verify whether endothelium dependent and/or independent function is altered in CADASIL patients with respect to controls. METHODS: Vasoreactivity was studied by a non-invasive pletismographic method in 49 mildly disabled CADASIL patients (30-65 years, 58% male, Rankin scale </=2) and 25 controls. Endothelium dependent vasodilatation was assessed by reactive hyperaemia (flow mediated dilation-peripheral arterial tone (FMD-PAT)) and endothelium independent vasoreactivity by glyceryl trinitrate (GTN) administration (GTN-PAT). RESULTS: Patients and controls showed comparable age, gender and cardiovascular risk factor distribution. GTN-PAT values were significantly lower in CADASIL patients (1.54 (1.01 to 2.25)) than in controls (1.89 (1.61 to 2.59); p=0.041). FMD-PAT scores did not differ between patients and controls (1.88 (1.57 to 2.43) vs 2.08 (1.81 to 2.58); p=0.126) but 17 CADASIL patients (35%) had FMD-PAT scores below the fifth percentile of controls. FMD-PAT and GTN-PAT values correlated both in controls (rho=0.648, p<0.001) and CADASIL patients (rho=0.563, p<0.001). By multivariable logistic regression for clinical and laboratory variables, only GTN-PAT (OR 0.39, 95% CI 0.15 to 0.97; p=0.044) was independently associated with FMD-PAT below the fifth percentile in CADASIL patients. CONCLUSIONS: The impaired vasoreactivity observed in CADASIL patients highlights the fact that both endothelial and smooth muscle functional alterations may already be present in mildly disabled subjects. The improvement in vascular function could be a new target for pharmacological trials in CADASIL patients.","Adult;Blood Vessels/physiopathology;Brain/pathology;CADASIL/*physiopathology;Case-Control Studies;Female;Humans;Magnetic Resonance Imaging;Male;Manometry;Middle Aged;Muscle, Smooth, Vascular/*physiopathology;Neuroimaging;Plethysmography","Campolo, J.;De Maria, R.;Frontali, M.;Taroni, F.;Inzitari, D.;Federico, A.;Romano, S.;Puca, E.;Mariotti, C.;Tomasello, C.;Pantoni, L.;Pescini, F.;Dotti, M. T.;Stromillo, M. L.;De Stefano, N.;Tavani, A.;Parodi, O.",2012,Mar,10.1136/jnnp-2011-300080,0,
5125,Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia,"Age-related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age- and sex-matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1-weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini-Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss.","Aged;Atrophy/etiology/pathology;Brain/ physiopathology;Cerebral Ventricles/ physiopathology;Cognition Disorders/diagnosis/etiology;Dementia/complications/ pathology;Dilatation;Female;Humans;Image Processing, Computer-Assisted;Longitudinal Studies;Magnetic Resonance Imaging;Male;Mental Status Schedule;Neuropsychological Tests;Parkinson Disease/complications/ pathology;Statistics as Topic;Time Factors","Camicioli, R.;Sabino, J.;Gee, M.;Bouchard, T.;Fisher, N.;Hanstock, C.;Emery, D.;Martin, W. R.",2011,Jul,10.1002/mds.23700,0,
5126,Neurobehcet. A presentation of three cases,"Introduction. Behcet's disease is a multisystemic illness in which neurological abnormalites are seen in 5-48% of cases. Clinical cases. We present 3 patients (2 men and 1 woman) diagnosed as having Behcet's disease, according to the criteria of the 'International Study Group for Behcet's Disease' of 1990. We describe the clinical findings in these patients, the results of investigations done (MR or CT, evoked potentials -PEV, PESS, PEATC- EEG, ECN, CSF and neuropsychological tests), their course and response to treatment with hyperimmune human gammaglobulim at a dose of 400 mg/kg body weight in 2 patients. All three patients had repeated episodes of meningitis and alterations of the cranial nerves; two patients had epileptic seizures and two had signs of cerebellar disorders and dementia at some time during their illness. One patient died and the other two survived with severe disabilities. Cranial CT showed a cerebral infarct in one patient; evoked potentials showed axon damage in the two patients in whom this was studied. In the only patient in whom ECN was done, signs of axonal polyneuropathy were found. In all three patients there was pleocytosis in the CSF. In the patients in whom hyperimmune human gammaglobulin was given, the results were: one improved after this treatment; in the other there was clinical deterioration, but this was considered to be secondary to a curettage done the day before. Conclusion. The presence of neurological findings in Behcet's disease not caused by cerebral vein thrombosis worsens the prognosis of these patients.",hyperimmune globulin;article;Behcet disease;brain infarction;case report;cerebellum disease;clinical feature;computer assisted tomography;dementia;electroencephalogram;evoked response;female;human;immunotherapy;intravenous drug administration;male;meningitis;neurologic disease;neuropsychological test;nuclear magnetic resonance imaging;pleocytosis;polyneuropathy;seizure,"Calzada-Sierra, D. J.",1999,,,0,
5127,Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial,"BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.",Cognition;Dementia;Exercise;Intervention;MRI brain;Type 2 diabetes,"Callisaya, M. L.;Daly, R. M.;Sharman, J. E.;Bruce, D.;Davis, T. M. E.;Greenaway, T.;Nolan, M.;Beare, R.;Schultz, M. G.;Phan, T.;Blizzard, L. C.;Srikanth, V. K.",2017,Oct 16,,0,
5128,Predicting Alzheimer's disease development: a comparison of cognitive criteria and associated neuroimaging biomarkers,"INTRODUCTION: The definition of ""objective cognitive impairment"" in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer's disease (AD) from baseline to 24 months. METHODS: The sensitivity and specificity of six methods of defining episodic memory impairment (< -1, -1.5 or -2 standard deviations [SD] on one or two memory tests) were compared in 494 non-demented seniors from the Alzheimer's Disease Neuroimaging Initiative using the area under the curve (AUC) for receiver operating characteristic analysis. The added value of non-memory measures (language and executive function) and biomarkers (hippocampal and white-matter hyperintensity volume, brain parenchymal fraction [BPF], and APOEepsilon4 status) was investigated using logistic regression. RESULTS: Baseline scores < -1 SD on two memory tests predicted AD with 75.91 % accuracy (AUC = 0.80). Only APOE epsilon4 status further improved prediction (B = 1.10, SE = 0.45, p = .016). A < -1.5 SD cut-off on one test had 66.60 % accuracy (AUC = 0.77). Prediction was further improved using Trails B/A ratio (B = 0.27, SE = 0.13, p = .033), BPF (B = -15.97, SE = 7.58, p = .035), and APOEepsilon4 status (B = 1.08, SE = 0.45, p = .017). A cut-off of < -2 SD on one memory test (AUC = 0.77, SE = 0.03, 95 % CI 0.72-0.82) had 76.52 % accuracy in predicting AD. Trails B/A ratio (B = 0.31, SE = 0.13, p = .017) and APOE epsilon4 status (B = 1.07, SE = 0.46, p = .019) improved predictive accuracy. CONCLUSIONS: Episodic memory impairment in MCI should be defined as scores < -1 SD below normative references on at least two measures. Clinicians or researchers who administer a single test should opt for a more stringent cut-off and collect and analyze whole-brain volume. When feasible, ascertaining APOE epsilon4 status can further improve prediction.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis/genetics/*pathology;Apolipoprotein E4/genetics;Area Under Curve;Brain/*pathology;Databases, Factual;Female;Follow-Up Studies;Humans;*Magnetic Resonance Imaging;Male;Memory Disorders/diagnosis/genetics/pathology;Memory, Episodic;Middle Aged;*Neuropsychological Tests;Prognosis;ROC Curve;Sensitivity and Specificity","Callahan, B. L.;Ramirez, J.;Berezuk, C.;Duchesne, S.;Black, S. E.",2015,,10.1186/s13195-015-0152-z,0,
5129,A case of fahr syndrome presenting with seizures,"Fahr syndrome is characterized with calcification in basal ganglia, dentate nucleus of cerebellum and centrum semiovale. Frequent clinical findings include Parkinsonism, dystonia, tremor, chorea, ataxia, dementia, and mood disorders. 13 years old male was admitted with generalized tonic-clonic seizures in our clinic. His neurological examination was normal. No abnormalities were determined in biochemical and hormonal examinations. Cranial computed tomography and magnetic resonance imaging demonstrated alterations in signal intensity suggestive of extensive calcifications in basal ganglia, thalami, periventricular white matter and centrum semiovale. Although, extra pyramidal system findings are the most common signs in Fahr syndrome, we aimed to point out that some of the patients might also present with epileptic seizures.",,"Çalık, M.;Abuhandan, M.;İşcan, A.;Çeçe, H.;Karakaş, E.",2015,,,0,
5130,"Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein ε4 Children Exposed to Air Pollution","Children's urban air pollution exposures result in systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most prevalent genetic risk for AD. We assessed whether APOE in healthy children modulates cognition, olfaction, and metabolic brain indices. The Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test were administered to 50 Mexico City Metropolitan Area children (13.4 ± 4.8 years, 28 APOE ε3 and 22 APOE ε4). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, and NAA/mI were calculated using proton magnetic resonance spectroscopy in the white matter of the frontal and parietal lobes, hippocampus, and pons. APOE ε4 versus ε3 children had a reduced NAA/Cr ratio in the right frontal white matter and decrements on attention, short-term memory, and below-average scores in Verbal and Full Scale IQ (>10 points). APOE modulated the group effects between WISC-R and left frontal and parietal white matter, and hippocampus metabolites. Soap was the predominantly failed odor in urban children and, in APOE ε4 versus ε3 carriers, strongly correlated with left hippocampus mI/Cr ratio. APOE modulates responses to air pollution in the developing brain. APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted environment. APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection and AD prevention.",apolipoprotein E4;choline;creatine;inositol;n acetylaspartic acid;adolescent;air pollution;article;brain metabolism;child;cognition;environmental exposure;female;frontal lobe;hippocampus;human;intelligence quotient;male;Mexico;nuclear magnetic resonance imaging;parietal lobe;pons;priority journal;proton nuclear magnetic resonance;short term memory;smelling;urban population;Wechsler intelligence scale;white matter,"Calderón-Garcidueñas, L.;Mora-Tiscareño, A.;Franco-Lira, M.;Zhu, H.;Lu, Z.;Solorio, E.;Torres-Jardón, R.;D'Angiulli, A.",2015,,,0,
5131,Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children,"Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9-24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases. © 2013 Calderón-Garcidueñas, Mora-Tiscareño, Franco-Lira, Cross, Engle, Aragón-Flores, Gómez-Garza, Jewells, Medina-Cortina, Solorio, Chao, Zhu, Mukherjee, Ferreira-Azevedo, Torres-Jardón and D'Angiulli.",endothelin 1;flavonol;gamma interferon inducible protein 10;granulocyte colony stimulating factor;interleukin 12;interleukin 1beta;interleukin 7;ozone;platelet derived growth factor AA;air pollution;air quality;article;basophil;cacao;child;cognition;diet supplementation;eosinophil count;female;hippocampus;human;human experiment;male;memory;Mexico;neuroprotection;neutrophil count;normal human;nuclear magnetic resonance spectroscopy;particulate matter;protein blood level;reticulocyte count;school child;scoring system;thrombocyte count;urban area;white matter,"Calderón-Garcidueñas, L.;Mora-Tiscareño, A.;Franco-Lira, M.;Cross, J. V.;Engle, R.;Aragón-Flores, M.;Gómez-Garza, G.;Jewells, V.;Medina-Cortina, H.;Solorio, E.;Chao, C. K.;Zhu, H.;Mukherjee, P. S.;Ferreira-Azevedo, L.;Torres-Jardón, R.;D'Angiulli, A.",2013,,,0,
5132,Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: Report on a case with morphometric studies,"Two previously distinct leukodystrophies, pigmentary orthochromatic leukodystrophy and hereditary diffuse leukoencephalopathy with spheroids, have recently been interpreted as variants of the same disease, adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP). We report a sporadic case of a 56-year-old male with ALSP presenting as frontotemporal dementia-behavioral variant (FTD-bv). He had a history of depression and developed socially inappropriate behaviors consistent with FTD-bv. His first neurological exam was normal, but he developed new symptoms in the next 1.5 years: executive functional difficulties, anosognosia, urinary incontinence, epilepsy, extrapyramidal syndrome, severe gait disturbance, dysarthria, dysphagia and mutism. He died of pneumonia 20 months after initial presentation. MRI revealed increased T2-FLAIR signal in periventricular white matter and corpus callosum atrophy. Histology showed extensive demyelination of the centrum semiovale, most severe in frontal and temporal lobes, sparing U-fibers. There was no cortical neuronal loss, but selective loss of thalamic neurons. Histopathological hallmarks were cortical neuronal ballooning, white matter orthochromasia, pigmented macrophages, oligodendroglial loss, and axonal spheroids, some myelinated and some vacuolated. Morphometric studies for myelin, spheroids, oligodendrocytes and astrocytes showed that: 1) spheroids were most abundant in areas of partial demyelination rather than areas of extensive demyelination, being absent in normal appearing areas, 2) oligodendrocyte loss only occurred in regions of extensive demyelination and not in partial demyelination, and 3) there was no statistically significant change in number of astrocytes. There were alsomany more spheroids than physiologically expected in the gracile and cuneate nuclei. These findings suggest that the formation of spheroids is an early-stage event in disease progression. ©2013 Dustri-Verlag Dr. K. Feistle.",alpha synuclein;amyloid precursor protein;myelin;tau protein;ubiquitin;adult;adult onset leukoencephalopathy with spheroid and pigmented glia;anosognosia;apathy;article;astrocyte;brain cortex;brain third ventricle;brain weight;case report;corpus callosum;daily life activity;daytime somnolence;death;decubitus;demyelination;depression;disease course;disease severity;dysarthria;dysphagia;epilepsy;extrapyramidal syndrome;frontotemporal dementia;gait disorder;genotype;glia;histopathology;human;iron blood level;lateral brain ventricle;leukoencephalopathy;macrophage;male;medical history;Mini Mental State Examination;morphometrics;mutism;myelin sheath;myelinated nerve;nuclear magnetic resonance imaging;oligodendroglia;onset age;parkinsonism;pneumonia;priority journal;psychosocial withdrawal;pyramidal sign;quadriplegia;seizure;spastic gait;temporal lobe;tumor spheroid;urinary tract infection;urine incontinence;verbal memory;white matter,"Calatayud, T.;Turkalp, Z. T.;Gonzales, A. A.;Munoz, D. G.",2013,,,0,
5133,Biopsy diagnosis of a case of adult onset orthochromatic leukodystrophy. Clinical and brain biopsy findings,"We report the intra vitam histopathological findings on the brain of a female patient presenting an adult form of orthochromatic leukodystrophy. At 38 years of age the patient began to show progressive dementia and a pseudobulbar syndrome. The pedigree revealed an autosomal dominant pattern of inheritance. The CT scan showed a wide hypodensity of the anterior white matter. Biochemical investigations showed only a slight elevation of serum VLCFA and no alteration of urinary enzymatic activities. Cortical and subcortical biopsy specimens from the right frontal lobe showed: neuronal loss in the gray matter, accumulation of autofluorescent material within residual neurons and sudanophilic material within macrophages and astrocytes, sparing of axons. Electron microscopy showed lamination and fragmentation of the myelin and the presence of electrondense bodies and vesicular material into oligodendrocytes and astrocytes. We discuss the differential diagnosis of OLD forms with adult onset, namely between Löwenberg-Hill disease and the pure form of OLD with pigmented glial cells.",article;biopsy;brain;brain disease;case report;computer assisted tomography;electron microscopy;female;genetics;human;middle aged;pathology;pedigree;radiography;ultrastructure,"Calandriello, L.;Matteucci, C.;Bertini, E.;Medolago Albani, L.;Antonelli, A.;Manfredi, M.;Palladini, G.",1992,,,0,
5134,Gait and stability disorders of the elderly. Clinical analysis of a series of 259 patients older than 70 years,"Introduction. Gait and stability disorders of the elderly are frequent and a cause of disability, but studies on their clinical features and etiology are scarce, including the relationship between both disorders. Objectives. To evaluate an extensive series of patients with gait and stability disorders, its clinical variants and posible pathogenic significance. Patients and methods. 259 patients older than 70 years consulting for chronic gait and stability symptoms in an outpatients neurologic clinic were retrospectively reviewed. Several clinical and evolution data are analyzed. Results. Mean age was 78.8 years and 61.8% were women. 52% were hypertensive. 161 cases had disequilibrium, 91 a cautious gait and seven other types of gait abnormality. 11% had associated dementia. 27% showed subcortical white matter abnormalities on computed tomography scan. In 28 cases a specific cause could be established. In follow-up 33.5% worsened. Significant differences between cases of disequilibrium and cautious gait were increased age, functional disability and turn abnormality in the latter. Conclusions. Disequilibrium and cautious gait of the elderly share some clinical features, have few specific causes and vary from mild cases to a disabling «encephalic gait disease».",aged;article;computer assisted tomography;dementia;gait disorder;human;hypertension;major clinical study;physical disability;white matter,"Calandre, L.;Conde, I.;Bermejo Pareja, F.",2005,,,0,
5135,"Is high oral dose L-arginine intake effective in leukoaraiosis? Preliminary data, study protocol and expert's opinion","BACKGROUND: Leukoraraiosis is worldwide considered as a part of the normal aging process, although it is strongly associated with dementia and other disabilities. The pathogenesis of leukoaraiosis still has not been thoroughly acknowledged, even though chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunction has been suggested. Treatment focuses on prevention of lesion formation and progression by aggressive control of risk factors, which should begin at an early age and continue on regular basis. Aim of our protocol is to evaluate the effect of long-term oral administration of high-dose L-arginine (6 g/day at least for 24 months) on white matter lesions and neurological and cognitive functions. MATERIALS AND METHODS: Patients affected by mild to moderate leukoaraiosis will be enrolled in the study. After a complete neurovascular assessment (i.e. accurate blood test examinations, Echocardiography, Doppler ultrasound of the neck and peripheral arteries), they will undergo MRI, specific neuropsychological tests and gait analysis. Patients will be evaluated at baseline, at 6, 12, 18 and 24 month-follow up. Statistical Analysis will be performed using the software R. A significant level of P<0.05 will be set for all the tests. PRELIMINARY DATA: Two of the 4 patients currently enrolled in the study presented a mild improvement in cognitive function. DISCUSSION: Because of its high prevalence in over-65-year-old subjects, we hypothesized that treatment with 6 gr of Larginine, as supplementary dietary option, could be helpful in patients affected by leukoaraiosis to improve the cognitive and gait impairment often observed in these subjects (as demonstrated by the LADIS study).","Administration, Oral;Arginine [administration & dosage] [pharmacology] [therapeutic use];Cognition Disorders [drug therapy] [pathology] [physiopathology];Cohort Studies;Dose-Response Relationship, Drug;Follow-Up Studies;Gait [drug effects] [physiology];Leukoaraiosis [drug therapy] [pathology] [physiopathology];Longitudinal Studies;Magnetic Resonance Imaging;Neuropsychological Tests;Outcome Assessment (Health Care);Prospective Studies;Treatment Outcome;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];aged;amnesia;article;brain cortex atrophy/dt [Drug Therapy];brain function;clinical article;cognition;cognitive defect;cohort analysis;controlled study;diarrhea/si [Side Effect];Doppler echocardiography;drug megadose;drug withdrawal;female;follow up;gait;human;leukoaraiosis/dt [Drug Therapy];male;Mini Mental State Examination;nausea/si [Side Effect];neuropsychological test;nuclear magnetic resonance imaging;observational study;priority journal;prospective study;randomized controlled trial;treatment refusal;white matter lesion/dt [Drug Therapy];arginine/ae [Adverse Drug Reaction];arginine/ct [Clinical Trial];arginine/do [Drug Dose];arginine/dt [Drug Therapy];arginine/po [Oral Drug Administration]","Calabro, R. S.;Gervasi, G.;Baglieri, A.;Furnari, A.;Marino, S.;Bramanti, P.",2013,,,0,
5136,Cadasil,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral vasculopathy progressing to subcortical dementia, caused by multiple lacunar infarcts and ischemic white matter degeneration. Migraine with aura, epileptic seizures and affective disorders are frequent additional symptoms of CADASIL. The causative mutations of the Notch3 gene are located on chromosome 19p13.1. There is complete penetrance of this disorder, although individual expression of symptoms may vary. Manifestation of CADASIL is usually in the 3(rd) decade, but some individuals remain asymptomatic close to the age of 60. MRI displays a marked leukoencephalopathy in affected individuals as early as in the age of 20. Frontal and subcortical hypoperfusion in demented individuals was demonstrated by SPECT-studies. The prevalence of CADASIL is still not known. To date there is no causative therapy.",affective neurosis;article;autosomal dominant inheritance;brain degeneration;brain infarction;cerebrovascular disease;chromosome 19p;dementia;gene mutation;human;leukoencephalopathy;migraine;nuclear magnetic resonance imaging;seizure,"Calabrese, P.;Roth, H.;Gehlen, W.;Mellies, J. K.",1999,,,0,
5137,Proton magnetic resonance spectroscopy in three subacute sclerosing panencephalitis patients: Correlation with clinical status,"Introduction: Subacute sclerosing panencephalitis is progressive, fatal encephalitis caused by a persistent defective measles virus in the central nervous system. The diagnosis is based upon characteristic clinical manifestations, the presence of characteristic periodic EEG discharges, and demonstration of elevated antibody titer against measles in the plasma and cerebrospinal fluid. There has been no correlation between the clinical status and the MRI findings. Methods: We performed single voxel magnetic resonance spectroscopy (MRS) on white matter areas that appeared normal or abnormal on conventional MRI in three patients with different clinical stages. Results: N-acetyl aspartate:creatine ratios were decreased and choline: creatine ratios were increased in white matter lesions in the late stages of the disease. A lactate peak was observed in a patient in the last stage of the disease. Increased myoinositol:creatine ratio was seen in white matter areas on conventional MRI and in the white matter lesions at early stage of the disease, before neuronal loss. © Springer-Verlag 2004.",alpha interferon;choline;creatine;inositol;lactic acid;measles antibody;methisoprinol;n acetylaspartic acid;anorexia;apathy;article;behavior disorder;brain atrophy;case report;cell loss;correlation function;dysphagia;electroencephalography;fatigue;gait disorder;health status;human;human cell;image analysis;imaging system;involuntary movement;irritability;male;measles;mental deterioration;mental performance;motor dysfunction;muscle weakness;myoclonus;nerve cell;nuclear magnetic resonance imaging;preschool child;priority journal;proton nuclear magnetic resonance;school child;slow brain wave;speech disorder;subacute sclerosing panencephalitis;urine incontinence;white matter;Intera,"Cakmakci, H.;Kurul, S.;Iscan, A.;Dirik, E.",2004,,,0,
5138,beta-Amyloid protein load is relatively uniform throughout neocortex and hippocampus in elderly Alzheimer's disease patients,"beta-Amyloid protein immunoreactivity in neocortex and hippocampus of Alzheimer's disease and control brains has been measured using an automatic image analysis system. Successive fields from the pial surface to white matter in 4 neocortical sites, parahippocampal gyrus and along the pyramidal cell layer in the hippocampus have been measured using a number of variables including: area fraction or load, counts per unit area and deposit size. In Alzheimer's disease beta-amyloid protein load in neocortex and hippocampus was significantly greater than in non-demented age-matched controls. beta-Amyloid protein load, as measured by size variables, was relatively uniform throughout the neocortex in elderly Alzheimer's disease patients. However, greater variability in deposition was measured in parahippocampal gyrus and hippocampus than in neocortex. Size and density variables used to measure beta-amyloid protein deposition were not correlated with age although there was a tendency for the cortical load to decrease with age beyond 80 years.","Aged;Aged, 80 and over;Alzheimer Disease/ metabolism;Amyloid beta-Peptides/ analysis/immunology;Cerebral Cortex/ chemistry;Female;Hippocampus/ chemistry;Humans;Male","Cairns, N. J.;Chadwick, A.;Luthert, P. J.;Lantos, P. L.",1991,Aug 5,,0,
5139,Atrophy of the temporal amygdala on MRI: Evaluation and specificity in Alzheimer's disease,"The aim of this prospective study was to assess the ability of MRI to measure the volume of the temporal amygdala and to evaluate the sensitivity and specificity of amygdala atrophy for the diagnosis of Alzheimer's disease by comparison with an age-matched control group and a group of patients with other forms of dementia. 33 patients (11 Alzheimer's disease, 16 other dementiae and 6 controls) were selected by strict clinical and radiological criteria. Examinations were performed on a 1.5 T MR scanner using 5 mm thickness coronal oblique T1 weighted contiguous slices perpendicular to the long axis of the temporal lobe. The volumetric measurements were performed independently and blindly by two radiologists and normalised to the median sagittal intracranial area. Inter-observer variation and right-left data were not significantly different. A significant atrophy of the temporal amygdala was noted in Alzheimer's disease in comparison to the other groups with a 43% (p < 0.01) difference with the controls and 41% (p < 0.001) difference with the other dementiae. By contrast, no significant difference existed between the controls and other dementiae. A significant inter-group overlap was noted between Alzheimer's disease and the other groups. This overlap decreases when patients with multi-infarct dementia due to major cerebrovascular disease are excluded from the other dementiae group. For an upper limit of normalised index of 815 mm, the specificity was 93% and sensitivity 91%. Comparing these results with those previously described in the literature, we conclude that the temporal amygdala atrophy is quite sensitive and specific for Alzheimer's disease and may be of diagnostic value, particularly in the early stages of the disease.",adult;aged;Alzheimer disease;article;brain atrophy;clinical article;controlled study;female;human;male;nuclear magnetic resonance imaging;temporal lobe,"Caillet, H.;Maunoury, C.;Denys, A.;Michot, J. L.;Parlato, V.;Jehenson, P.;Boller, F.;Syrota, A.",1994,,,0,
5140,Modulation on brain gray matter activity and white matter integrity by APOE ε4 risk gene in cognitively intact elderly: A multimodal neuroimaging study,"Apolipoprotein E (APOE) ε4 allele is the genetic risk factor with the most established evidence for sporadic Alzheimer's disease. Previous neuroimaging studies have demonstrated insufficiently consistent functional and structural changes among healthy APOE ε4 carriers when compared to non-carriers. Here, in a cognitively intact elderly group (a total of 110: 45 APOE ε4 carriers, 65 non-carriers), we aimed to investigate the potential role of APOE ε4 in the modulation of grey matter activity, white matter integrity, and brain morphology before the development of clinically significant symptoms and signs, by methods of: amplitude of low frequency fluctuations and regional homogeneity analysis based on resting state fMRI, and fiber tractography approach based on diffusion tensor imaging. Our results revealed that compared to non-carriers, APOE ε4 carriers showed: (1) an inconsistent pattern of activity change in the default mode network, including increased gray matter activity in anterior cingulate cortex and medial prefrontal cortex and decreased activity in precuneus; (2) lower mean diffusivity (MD) in fibers of corona radiata and corpus callosum, and lower axial diffusivity in genu of corpus callosum; and (3) significant positive correlation between the MD value of the right superior corona radiate and gross white matter volume; significant negative correlation between the MD value of the right superior corona radiate and Mini-Mental State Examination (MMSE) score. Our results suggested that APOE ε4 gene can modulate gray matter activity and white matter integrity in cognitive and memory related regions, even before any clinical or neuropsychic symtoms or signs of imminent disease.",apolipoprotein E4;aged;amplitude of low frequency fluctuation;anterior cingulate;APOE epsilon 4 gene;article;BOLD signal;controlled study;corona radiata (brain);corpus callosum;default mode network;diffusion tensor imaging;female;functional magnetic resonance imaging;genetic risk;gray matter;human;male;medial prefrontal cortex;Mini Mental State Examination;neuroimaging;neurologic examination;precuneus;regional homogeneity;white matter,"Cai, S.;Jiang, Y.;Wang, Y.;Wu, X.;Ren, J.;Lee, M. S.;Lee, S.;Huang, L.",2017,,10.1016/j.bbr.2017.01.027,0,
5141,"Synthesis and evaluation of two 18F-labeled 6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo 1,2-a pyridine derivatives as prospective radioligands for beta-amyloid in Alzheimer's disease","This study evaluated (18)F-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K(i) = 27 +/- 8 and 40 +/- 5 nM, respectively. A ""one-pot"" method for (18)F-2-fluoroethylation and (18)F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [(18)F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [(18)F]FPM-IMPY at 0.8 min. These values were similar to those of [(123)I/(125)I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [(18)F]FEM or [(18)F]FPM-IMPY. In contrast to the single-exponential washout of [(123)I/(125)I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [(18)F]FEM-IMPY and 2.1% ID/g for [(18)F]FPM-IMPY. Substantial skull uptake of [(18)F]fluoride was also clearly observed. With a view to slow the metabolism of [(18)F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D(4)-[(18)F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [(18)F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [(18)F]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity.","Alzheimer Disease/metabolism/ radionuclide imaging;Amyloid beta-Peptides/chemistry/ metabolism;Animals;Autoradiography;Brain/metabolism/radionuclide imaging;Chromatography, Liquid;Female;Fluorine Radioisotopes;Humans;Imidazoles/ chemical synthesis/metabolism;In Vitro Techniques;Isotope Labeling;Ligands;Macaca mulatta;Male;Mice;Middle Aged;Peptide Fragments/chemistry/metabolism;Pyridines/ chemical synthesis/metabolism;Spectrometry, Mass, Electrospray Ionization;Tissue Distribution;Tomography, Emission-Computed","Cai, L.;Chin, F. T.;Pike, V. W.;Toyama, H.;Liow, J. S.;Zoghbi, S. S.;Modell, K.;Briard, E.;Shetty, H. U.;Sinclair, K.;Donohue, S.;Tipre, D.;Kung, M. P.;Dagostin, C.;Widdowson, D. A.;Green, M.;Gao, W.;Herman, M. M.;Ichise, M.;Innis, R. B.",2004,Apr 22,10.1021/jm030477w,0,
5142,The feasibility of quantitative MRI of perivascular spaces at 7T,"BACKGROUND: Dilated brain perivascular spaces (PVSs) are found to be associated with many conditions, including aging, dementia, and Alzheimer's disease (AD). Conventionally, PVS assessment is mainly based on subjective observations of the number, size and shape of PVSs in MR images collected at clinical field strengths (</=3T). This study tests the feasibility of imaging and quantifying brain PVS with an ultra-high 7T whole-body MRI scanner. NEW METHOD: 3D high resolution T2-weighted brain images from healthy subjects (n=3) and AD patients (n=5) were acquired on a 7T whole-body MRI scanner. To automatically segment the small hyperintensive fluid-filling PVS structures, we also developed a quantitative program based on algorithms for spatial gradient, component connectivity, edge-detection, k-means clustering, etc., producing quantitative results of white matter PVS volume densities. RESULTS: The 3D maps of automatically segmented PVS show an apparent increase in PVS density in AD patients compared to age-matched healthy controls due to the PVS dilation (8.0+/-2.1 v/v% in AD vs. 4.9+/-1.3 v/v% in controls, p<0.05). COMPARISON WITH EXISTING METHOD: We demonstrated that 7T provides sufficient SNR and resolution for quantitatively measuring PVSs in deep white matter that is challenging with clinical MRI systems (</=3T). Compared to the conventional visual counting and rating for the PVS assessment, the quantitation method we developed is automatic and objective. CONCLUSIONS: Quantitative PVS MRI at 7T may serve as a non-invasive and endogenous imaging biomarker for diseases with PVS dilation.",,"Cai, K.;Tain, R.;Das, S.;Damen, F. C.;Sui, Y.;Valyi-Nagy, T.;Elliott, M. A.;Zhou, X. J.",2015,Dec 30,10.1016/j.jneumeth.2015.09.001,0,
5143,A frameshift mutation in HTRA1 expands CARASIL syndrome and peripheral small arterial disease to the Chinese population,"Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare hereditary cerebral artery disease. The HtrA serine protease 1 (HTRA1) gene has been identified as the causative gene of CARASIL. Here, we report a novel mutation in the HTRA1 gene in a CARASIL pedigree and explore its pathogenesis at the protein level. Subcutaneous tissue biopsy and HTRA1 gene analysis were performed in a CARASIL patient, and HTRA1 and TGF-β1 protein expression in subcutaneous tissue and cultured fibroblasts from the proband were detected by immunohistochemistry and western blotting. A 28-year-old male proband and his brother experienced recurrent stroke, hair loss and low back pain. Abnormalities in the proband were found in the elastic plate of subcutaneous small arteries, and a novel homozygous frameshift mutation (c.161_162insAG), leading to the formation of a stop codon 159 amino acids downstream of the insertion (p.Gly56Alafs*160) was detected. Reduced HTRA1 protein and increased TGF-β1 expression were detected in subcutaneous tissue and in cultured fibroblasts. A frameshift mutation in the HTRA1 gene detected in a CARASIL pedigree resulted in reduced HTRA1 protein and increased TGF-β1 expression, which may cause severe CARASIL and peripheral small arterial disease.",htra serine protease 1;meprednisone;prednisone;serine proteinase;transforming growth factor beta1;unclassified drug;adult;alopecia;artery intima proliferation;article;autosomal recessive disorder;Babinski reflex;brain hemorrhage;brain infarction;brain perfusion;CADASIL;case report;cerebral artery disease;cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy;clonus;computer assisted tomography;controlled study;Doppler echography;fibroblast culture;follow up;frameshift mutation;hair loss;Han Chinese;homozygote;human;human tissue;immobility;immunohistochemistry;leukoencephalopathy;limb weakness;low back pain;lumbar disk hernia;male;molecular pathology;multiple sclerosis;neuroimaging;neuropathology;nuclear magnetic resonance imaging;paresthesia;pedigree;peripheral occlusive artery disease;protein expression;pseudobulbar palsy;pyramidal sign;quadriplegia;rare disease;recurrent disease;single photon emission computer tomography;stop codon;subcortex;subcutaneous tissue;thigh numbness;vertebral artery;Western blotting;methylprednisone,"Cai, B.;Zeng, J.;Lin, Y.;Lin, Y.;Lin, W. P.;Lin, W.;Li, Z.;Wang, N.",2015,,,0,
5144,Cognitive and neuroimaging predictors of instrumental activities of daily living,"Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.","*Activities of Daily Living;Aged;Aged, 80 and over;Case-Control Studies;Cognition/*physiology;Cognition Disorders/pathology/physiopathology/psychology;Dementia/pathology/physiopathology/psychology;Female;Humans;Magnetic Resonance Imaging/*methods;Male;Neuropsychological Tests;Predictive Value of Tests;Problem Solving/*physiology;Psychomotor Performance/*physiology","Cahn-Weiner, D. A.;Farias, S. T.;Julian, L.;Harvey, D. J.;Kramer, J. H.;Reed, B. R.;Mungas, D.;Wetzel, M.;Chui, H.",2007,Sep,10.1017/s1355617707070853,0,
5145,Isolated degenerative amnesia without dementia: An 8-year longitudinal study,"A case of a 72-year-old patient suffering from progressive isolated memory disorders is reported. The patient has been followed up over eight years and her neuropsychological profile reveals a high standard of performance on all tests assessing intelligence, language, praxis, attention, and short-term memory, but she fails all long-term memory tasks. MRI images showed bilateral hippocampal atrophy in the sagittal and coronal sections in the absence of white matter signal abnormalities. [(18)FDG] PET scan detected bilateral hypometabolism of the hippocampal regions and of the thalamus and mild metabolic reduction in the frontal area. The neuroimaging and neuropsychological profiles point to a progressive amnesia of degenerative aetiology.",,"Caffarra, P.;Venneri, A.",1996,1996,,0,
5146,"Rust on the Brain from Microbleeds and Its Relevance to Alzheimer Studies: Invited Commentary on Cacciottolo Neurobiology of Aging, 2016","Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on sex-ApoE interactions in MBs published this February, briefly explores three aspects of MBs that could not be fully discussed therein: I, A possible gap between the prevalence of MBs as detected by MRI and post mortem analysis; II, The role of hemoglobin-degradation products in amyloid-attributed neurodegenerative changes; and III, Possible assessment of MB by cerebrospinal fluid (CSF) assays for iron-related markers to better screen patient subgroups for AD interventions.",Alzheimer disease;CSF heme;Microbleeds;Transgenic mice,"Cacciottolo, M.;Morgan, T. E.;Finch, C. E.",2016,Nov,,0,
5147,The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice,"The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Abeta also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Abeta load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition.",,"Cacciottolo, M.;Christensen, A.;Moser, A.;Liu, J.;Pike, C. J.;Smith, C.;LaDu, M. J.;Sullivan, P. M.;Morgan, T. E.;Dolzhenko, E.;Charidimou, A.;Wahlund, L. O.;Wiberg, M. K.;Shams, S.;Chiang, G. C.;Finch, C. E.",2016,Jan,10.1016/j.neurobiolaging.2015.10.010,0,
5148,White matter microstructure and apathy level in amnestic mild cognitive impairment,"In this study, we assess white matter microstructural deficit correlates of apathy level in 20 patients with amnestic mild cognitive impairment by means of diffusion tensor imaging. Mean diffusivity correlated positively with apathy level in the right temporal portion of the uncinate, middle longitudinal and inferior longitudinal fasciculi and in the parathalamic white matter, the fornix and the posterior cingulum of the right hemisphere. Fractional anisotropy results confirmed evidence of disconnection associated with apathy in all white matter areas except the middle longitudinal fasciculus. These results support the view that alterations in the neural mechanisms underlying apathy level occur in the early phase of degenerative dementias.","Affective Symptoms/ etiology;Aged;Amnesia/ complications/ pathology;Anisotropy;Brain Mapping;Cognition Disorders/ complications/ pathology;Diffusion Tensor Imaging/methods;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests","Cacciari, C.;Moraschi, M.;Di Paola, M.;Cherubini, A.;Orfei, M. D.;Giove, F.;Maraviglia, B.;Caltagirone, C.;Spalletta, G.",2010,,10.3233/jad-2010-1384,0,
5149,"Head-to-head comparison of 11C-PiB and 18F-FC119S for Aβ imaging in healthy subjects, mild cognitive impairment patients, and Alzheimer's disease patients","As a new beta amyloid (Aβ) positron emission tomography (PET) tracer, 18F-FC119S has shown higher cortical uptake in patients with Alzheimer's disease (AD) than that in healthy control subjects without adverse effects in a previous preliminary study. The aim of this study was to compare 18F-FC119S PET and 11C-PiB PET in healthy control (HC) subjects, mild cognitive impairment (MCI) patients, and AD patients. A total of 48 subjects, including 28 HC subjects, 10 MCI patients, and 10 AD patients, underwent static 18F-FC119S PET (30 minutes after intravenous [i.v.] injection) and 11C-PiB PET (40 minutes after i.v. injection) on the same day. Both PET images were visually and quantitatively assessed. Standardized uptake value ratios (SUVRs) were calculated for each brain region using the cerebellar cortex as a reference region. None (0%) of the 28 HC subjects and 4 (40%) of 10 MCI patients had positive scans on both PET images. Of the 10 AD patients, 7 (70%) had positive scans on 11C-PiB PET while 6 (60%) had positive scans on 18F-FC119S PET. Overall, 47 (98%) of 48 participants showed identical results based on visual analysis. Cortical SUVR of 18F-FC119S was higher in AD patients (1.38±0.16), followed by that in MCI patients (1.24±0.10) and in HC subjects (1.14±0.05). Compared with 11C-PiB PET, 18F-FC119S PET yielded a higher effect size (d=2.02 vs. 1.67) in AD patients and a slightly lower effect size (d=1.26 vs. 1.38) in MCI patients. In HC subjects, the nonspecific binding of 18F-FC119S to white matter (with the frontal cortex-to-white matter SUV ratio of 0.76) was slightly lower than that of 11C-PiB (ratio of 0.73). There was a significant linear correlation (slope=0.41, r=0.78, P<0.001) between 11C-PiB and 18FFC119S cortical SUVR. We could safely obtain images similar to 11C-PiB PET imaging Ab in the brain using 18F-FC119S PET. Therefore, 18F-FC119S might be suitable for imaging Ab deposition.",amyloid beta protein;FC119S f 18;Pittsburgh compound B;tracer;unclassified drug;absence of side effects;adult;Alzheimer disease;article;caudate nucleus;cerebellum cortex;clinical article;controlled study;female;frontal cortex;human;male;middle aged;mild cognitive impairment;neuroimaging;nuclear magnetic resonance imaging;PET-CT scanner;positron emission tomography-computed tomography;priority journal;putamen;quantitative analysis;white matter;Biograph 6 TruePoint TrueV scanner;MAGNETOM Trio A Tim,"Byun, B. H.;Kim, B. I.;Park, S. Y.;Ko, I. O.;Lee, K. C.;Kim, K. M.;Kim, Y. K.;Lee, J. Y.;Bu, S. H.;Kim, J. H.;Chi, D. Y.;Ha, J. H.;Lim, S. M.",2017,,10.1097/md.0000000000006441,0,
5150,"Head-to-head comparison of 11C-PiB and 18F-FC119S for Abeta imaging in healthy subjects, mild cognitive impairment patients, and Alzheimer's disease patients","As a new beta amyloid (Abeta) positron emission tomography (PET) tracer, F-FC119S has shown higher cortical uptake in patients with Alzheimer's disease (AD) than that in healthy control subjects without adverse effects in a previous preliminary study. The aim of this study was to compare F-FC119S PET and C-PiB PET in healthy control (HC) subjects, mild cognitive impairment (MCI) patients, and AD patients.A total of 48 subjects, including 28 HC subjects, 10 MCI patients, and 10 AD patients, underwent static F-FC119S PET (30 minutes after intravenous [i.v.] injection) and C-PiB PET (40 minutes after i.v. injection) on the same day. Both PET images were visually and quantitatively assessed. Standardized uptake value ratios (SUVRs) were calculated for each brain region using the cerebellar cortex as a reference region.None (0%) of the 28 HC subjects and 4 (40%) of 10 MCI patients had positive scans on both PET images. Of the 10 AD patients, 7 (70%) had positive scans on C-PiB PET while 6 (60%) had positive scans on F-FC119S PET. Overall, 47 (98%) of 48 participants showed identical results based on visual analysis. Cortical SUVR of F-FC119S was higher in AD patients (1.38 +/- 0.16), followed by that in MCI patients (1.24 +/- 0.10) and in HC subjects (1.14 +/- 0.05). Compared with C-PiB PET, F-FC119S PET yielded a higher effect size (d = 2.02 vs. 1.67) in AD patients and a slightly lower effect size (d = 1.26 vs. 1.38) in MCI patients. In HC subjects, the nonspecific binding of F-FC119S to white matter (with the frontal cortex-to-white matter SUV ratio of 0.76) was slightly lower than that of C-PiB (ratio of 0.73). There was a significant linear correlation (slope = 0.41, r = 0.78, P < 0.001) between C-PiB and F-FC119S cortical SUVR.We could safely obtain images similar to C-PiB PET imaging Abeta in the brain using F-FC119S PET. Therefore, F-FC119S might be suitable for imaging Abeta deposition.",,"Byun, B. H.;Kim, B. I.;Park, S. Y.;Ko, I. O.;Lee, K. C.;Kim, K. M.;Kim, Y. K.;Lee, J. Y.;Bu, S. H.;Kim, J. H.;Chi, D. Y.;Ha, J. H.;Lim, S. M.",2017,Mar,,0,
5151,Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis,"BACKGROUND: Blood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. METHODS: We did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study. We studied associations between NfL concentrations in plasma and clinical and MRI neuroimaging findings, namely cognitive function, motor function, and brain volume (global and regional). We used random effects models to analyse cross-sectional associations at each study visit and to assess changes from baseline, with and without adjustment for age and CAG repeat count. In an independent London-based cohort of 37 participants (23 HTT mutation carriers and 14 controls), we further assessed whether concentrations of NfL in plasma correlated with those in CSF. FINDINGS: Baseline and follow-up plasma samples were available from 97 controls and 201 individuals carrying HTT mutations. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls (3.63 [SD 0.54] log pg/mL vs 2.68 [0.52] log pg/mL, p<0.0001) and the difference increased from one disease stage to the next. At any given timepoint, NfL concentrations in plasma correlated with clinical and MRI findings. In longitudinal analyses, baseline NfL concentration in plasma also correlated significantly with subsequent decline in cognition (symbol-digit modality test r=-0.374, p<0.0001; Stroop word reading r=-0.248, p=0.0033), total functional capacity (r=-0.289, p=0.0264), and brain atrophy (caudate r=0.178, p=0.0087; whole-brain r=0.602, p<0.0001; grey matter r=0.518, p<0.0001; white matter r=0.588, p<0.0001; and ventricular expansion r=-0.589, p<0.0001). All changes except Stroop word reading and total functional capacity remained significant after adjustment for age and CAG repeat count. In 104 individuals with premanifest Huntington's disease, NfL concentration in plasma at baseline was associated with subsequent clinical onset during the 3-year follow-up period (hazard ratio 3.29 per log pg/mL, 95% CI 1.48-7.34, p=0.0036). Concentrations of NfL in CSF and plasma were correlated in mutation carriers (r=0.868, p<0.0001). INTERPRETATION: NfL in plasma shows promise as a potential prognostic blood biomarker of disease onset and progression in Huntington's disease. FUNDING: Medical Research Council, GlaxoSmithKline, CHDI Foundation, Swedish Research Council, European Research Council, Wallenberg Foundation, and Wolfson Foundation.","0 (Biomarkers);0 (HTT protein, human);0 (Huntingtin Protein);0 (Neurofilament Proteins);0 (neurofilament protein L);Adult;Aged;Atrophy/pathology;Biomarkers/blood;Brain/ diagnostic imaging;Cognitive Dysfunction/ blood/etiology/physiopathology;Disease Progression;Follow-Up Studies;Humans;Huntingtin Protein/genetics;Huntington Disease/ blood/diagnostic imaging/genetics;Middle Aged;Neurofilament Proteins/ blood;Retrospective Studies;Trinucleotide Repeat Expansion;Young Adult","Byrne, L. M.;Rodrigues, F. B.;Blennow, K.;Durr, A.;Leavitt, B. R.;Roos, R. A. C.;Scahill, R. I.;Tabrizi, S. J.;Zetterberg, H.;Langbehn, D.;Wild, E. J.",2017,Aug,,0,
5152,Ratio of urine albumin to creatinine attenuates the association of dementia with hip fracture risk,"CONTEXT: Microvascular disease is a leading cause of cognitive impairment. Approximately 50% of people with a hip fracture have cognitive impairment. OBJECTIVE: We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [>/= 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk. SETTING: The Cardiovascular Health Cognition Study. PATIENTS: Three thousand, one-hundred six participants (mean age, approximately 79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098). MAIN OUTCOME MEASURE: Incident hip fracture. RESULTS: There were 488 participants (16%) with mild cognitive impairment (MCI) and 564 (18%) with dementia. There were 337 incident hip fractures, of which 19% occurred in participants with MCI and 26% in participants with dementia. Adjusted hazard ratios (HR) and 95% confidence interval for hip fracture in participants with MCI were 2.45 (1.67-3.61) and for dementia 2.35 (1.57-3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55-0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk. CONCLUSIONS: ACR attenuates part of the risk of hip fracture in people with dementia, suggesting that these disorders share a common pathogenesis.","Aged;Aged, 80 and over;Albuminuria/complications/ urine;Creatinine/ urine;Dementia/epidemiology/ etiology/urine;Female;Hip Fractures/epidemiology/ etiology/urine;Humans;Incidence;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/epidemiology/ etiology/urine;Neuropsychological Tests;Prospective Studies;Risk","Buzkova, P.;Barzilay, J. I.;Fink, H. A.;Robbins, J. A.;Cauley, J. A.;Fitzpatrick, A. L.",2014,Nov,10.1210/jc.2014-2409,0,
5153,Vascular dementia: stroke prevention takes on new urgency,"Vascular dementia is a clinical syndrome of acquired intellectual impairment resulting from brain injury due to a cerebrovascular disorder. It is a complex diagnosis, and diagnostic criteria vary. In community practice, the physician can probably make the diagnosis based on the history and medical examination. CT demonstration of one or more infarcts increases the likelihood of this diagnosis. Hypertension is a major risk factor for vascular dementia. Others include smoking, hyperlipidemia, atrial fibrillation, diabetes, and a sedentary lifestyle. Cerebrovascular disease is an important cause of cognitive decline in older patients. Therefore, it is important to recognize risk factors for stroke and institute measures for prevention.","Aged;Cerebrovascular Disorders/*prevention & control;Dementia, Vascular/*diagnosis/*etiology;Humans;Hypertension/*complications;Prognosis;Risk Factors;Tomography, X-Ray Computed","Butler, R. N.;Ahronheim, J.;Fillit, H.;Rapoport, S. I.;Tatemichi, J. K.",1993,Nov,,0,
5154,Differentiation between Alzheimer's disease and multi-infarct dementia: SPECT vs MR imaging,"Single photon emission computed tomography (SPECT) and magnetic resonance (MR) imaging data were obtained in 11 patients with dementia of the Alzheimer type (DAT), 11 with multi-infarct dementia (MID) and nine elderly, healthy controls. All patients with dementia tolerated a 15-minute SPECT scan while six patients (27%) did not tolerate the MR examination due to the long acquisition times and/or claustrophobia. Blind qualitative rating of SPECT scans differentiated correctly between dementia and controls in 90% of cases (p < 0.0001; positive predicted value of 91%) and between clinically defined DAT and MID in 77% of cases (p < 0.01; positive predicted value of 80%). It correctly identified clinical group membership (control, DAT or MID) in 71% of cases (p < 0.0001). Blind qualitative MR imaging analysis differentiated between dementia and controls in 91% of cases (p < 0.001; predicted positive value of 94%) but failed to differentiate between DAT and MID (positive predicted value of 50%). Overall, MR imaging correctly identified clinical group membership in 61% of cases (p < 0.01). Semiquantitative SPECT data demonstrated reduced regional cerebral blood flow (rCBF) in all regions of interest (ROI) except right frontal and right anterior parietal in both DAT and MID compared with controls (p < 0.05). There was no statistically significant difference between DAT and MID subjects in rCBF in any ROI. Several correlations between rCBF and cognitive variables were found in the MID but not the DAT group. Though the sample in this study is small, our findings suggest that Tc-99m HMPAO SPECT is a useful and practical tool in the assessment of patients with dementia. It enables the differential diagnosis of dementia and by using semiquantitative data it helps to establish the severity of disease.",,"Butler, R. E.;Costa, D. C.;Greco, A.;Ell, P. J.;Katona, C. L. E.",1995,1995,,0,
5155,"Adaptation of dementia testing for vision-impaired individuals - Administration of the structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia and dementias of other etiology (SIDAM)","In epidemiological field studies on the prevalence and incidence of dementia, the problem of cognitive testing of visually impaired individuals is rarely discussed. In the Leipzig Longitudinal Study of the Aged (LEILA 75+) a version of the SIDAM (SIDAM - Structured Interview for the Diagnosis of dementia of the Alzheimer type, Multi-infarct dementia and dementias of other etiology) for the visually impaired was employed from which all items requiring image processing had been omitted (SIDAM-blind). In order to be able to interpret the test results, the final scores for the full SIDAM were estimated by linear transformation of the scores in the blind-version. The method of linear transformation is based on certain theoretical assumptions which are examined in this paper. Linear transformation of scores has proved to be a valid procedure only for individuals with high cognitive performances. Thus, an evaluation of estimated scores based on the norms for the original SIDAM has limitations. Consequently, age-specific norms for the SIDAM-blind are presented. Sensitivities and specificities for different cut-off points used to discriminate between demented and non-demented vision-impaired individuals are given.",,"Busse, A.;Aurich, C.;Riedel-Heller, S.;Matschinger, H.;Angermeyer, M. C.",2002,2002,,0,
5156,"Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging","OBJECTIVE: The objective of this study was to investigate cross-sectional and longitudinal white matter hyperintensity (WMH) changes in older subjects with clinically diagnosed dementia. METHODS: Fluid-attenuated inversion recovery images were acquired one year apart in subjects with dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Alzheimer disease (AD), and also healthy elderly comparison subjects. WMH volume was quantified using an automated technique. RESULTS: Baseline WMH (as a percent of brain volume) was significantly greater compared with healthy subjects (N=33, geometric mean WMH: 0.4%) in subjects with AD (N=23 [1.3%], analysis of variance post hoc p <0.001) but not PDD (N=13 [0.6%]) or DLB (N=14 [0.4%]). Increase in WMH volume (as a percent of brain volume) was not significantly different (Kruskal-Wallis p=0.4) between groups (AD median change: 0.08%; DLB: 0.025%; PDD: 0.07%, healthy: 0.02%). Severity of baseline WMH, rather than diagnosis or severity of dementia, was a significant predictor of lesion progression. Rate of change of WMH had no association with change in global cognitive performance. CONCLUSIONS: Significant WMH progression occurs in degenerative dementias with rates influenced by severity of lesions at baseline rather than dementia type or cognitive decline.",Aged;Aging/ physiology;Alzheimer Disease/epidemiology/ pathology;Brain/ pathology;Cognition Disorders/diagnosis/epidemiology;Demography;Disease Progression;Female;Follow-Up Studies;Humans;Lewy Body Disease/epidemiology/ pathology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Parkinson Disease/epidemiology/ pathology;Prospective Studies;Severity of Illness Index,"Burton, E. J.;McKeith, I. G.;Burn, D. J.;Firbank, M. J.;O'Brien, J. T.",2006,Oct,10.1097/01.JGP.0000236596.56982.1c,0,
5157,Hyperintensities and fronto-subcortical atrophy on MRI are substrates of mild cognitive deficits after stroke,"Aim: The current study determines the MRI correlations of the early neuropsychological post-stroke cognitive deficits. Method: Detailed neuropsychological assessments (attention and working memory) were undertaken in 50 stroke survivors > 75 years of age [38 with ageing-associated cognitive decline (AACD)] and 15 age-matched controls. A 1.5-tesla General Electric MRI scanner was used. Standardized visual ratings were undertaken of white matter hyperintensities (WMH). Grey matter volumes were assessed using voxel-based morphometery. Results: Associations were identified between processing speed and executive function and the severity of WMH in key areas. In addition, atrophy in the fronto-subcortical circuits was associated with AACD. Conclusion: Attentional and executive impairments are underpinned by WMH in fronto-striato-thalamo-frontal circuits. Frontal atrophy is identified as a novel substrate of cognitive decline in stroke patients. Copyright © 2003 S. Karger AG, Basel.",aged;aging;article;attention;brain atrophy;brain function;brain size;clinical article;cognitive defect;controlled study;disease association;female;gray matter;human;male;morphometrics;neuropsychological test;neuropsychology;nuclear magnetic resonance imaging;outcomes research;priority journal;standardization;cerebrovascular accident;white matter;working memory,"Burton, E.;Ballard, C.;Stephens, S.;Kenny, R. A.;Kalaria, R.;Barber, R.;O'Brien, J.",2003,,,0,
5158,Childhood Trauma and PTSD Symptoms Increase the Risk of Cognitive Impairment in a Sample of Former Indentured Child Laborers in Old Age,"A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood. © 2013 Burri et al.",aged;article;child labor;childhood trauma;cognitive defect;cohort analysis;depression;disease association;DSM-III-R;early life stress;female;human;ICD-10;major clinical study;male;memory;Mini Mental State Examination;neuropsychological test;posttraumatic stress disorder;psychotrauma;Switzerland,"Burri, A.;Maercker, A.;Krammer, S.;Simmen-Janevska, K.",2013,,,0,
5159,Reduced lean mass in early Alzheimer disease and its association with brain atrophy,"OBJECTIVE: To examine body composition in individuals with early AD and without dementia and its relation to cognition and brain volume. DESIGN: Cross-sectional case-control study. PARTICIPANTS: Individuals without dementia (Clinical Dementia Rating, 0; n = 70) and with early-stage AD (Clinical Dementia Rating, 0.5 or 1; n = 70) in the Alzheimer and Memory Program at the University of Kansas School of Medicine. MAIN OUTCOME MEASURES: Participants were evaluated with brain magnetic resonance imaging (MRI), neuropsychological testing, and dual-energy x-ray absorptiometry to determine whole-body fat and lean masses. Body mass index was calculated as weight in kilograms divided by height in meters squared. RESULTS: Lean mass was reduced in persons with early AD compared with controls without dementia (F = 7.73; P = .006) after controlling for sex. Whole-brain volume (beta = .20; P < .001), white matter volume (beta = .19; P < .001), and global cognitive performance (beta = .12; P = .007) were associated with lean mass (dependent variable) when controlling for age and sex. The total body fat and percentage of body fat values were not different across groups or related to cognition and brain volume. CONCLUSION: Loss of lean mass is accelerated in AD and is associated with brain atrophy and cognitive performance, perhaps as a direct or indirect consequence of AD pathophysiology or through shared mechanisms common to both AD and sarcopenia.","Absorptiometry, Photon;Adipose Tissue/physiology;Aged;Alzheimer Disease/ epidemiology/pathology;Atrophy/epidemiology/pathology;Biomarkers/analysis;Body Mass Index;Brain Mapping;Case-Control Studies;Cognition Disorders/epidemiology/pathology;Comorbidity;Cross-Sectional Studies;Disability Evaluation;Disease Progression;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Muscle, Skeletal/pathology/physiopathology;Neuropsychological Tests;Sarcopenia/ epidemiology/pathology/radiography;Thinness/ epidemiology/pathology/radiography;Weight Loss/physiology","Burns, J. M.;Johnson, D. K.;Watts, A.;Swerdlow, R. H.;Brooks, W. M.",2010,Apr,10.1001/archneurol.2010.38,0,
5160,Cardiorespiratory fitness and brain atrophy in early Alzheimer disease,"OBJECTIVE: To examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer disease (AD). BACKGROUND: In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known. METHODS: Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO(2)(peak)), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance. RESULTS: Cardiorespiratory fitness (VO(2)(peak)) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO(2)(peak) was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO(2)(peak) was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age. CONCLUSIONS: Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.","Aged;Aged, 80 and over;Aging/pathology/physiology;Alzheimer Disease/*pathology/*physiopathology/psychology;Atrophy;Brain/*pathology/*physiopathology;Cognition/physiology;Cross-Sectional Studies;*Exercise Test/methods;Female;Humans;Male;Physical Fitness/*physiology;Respiratory Mechanics/*physiology;Time Factors","Burns, J. M.;Cronk, B. B.;Anderson, H. S.;Donnelly, J. E.;Thomas, G. P.;Harsha, A.;Brooks, W. M.;Swerdlow, R. H.",2008,Jul 15,10.1212/01.wnl.0000317094.86209.cb,0,
5161,White matter lesions are prevalent but differentially related with cognition in aging and early Alzheimer disease,"BACKGROUND: White matter lesions (WMLs) are prevalent in nondemented aging and in Alzheimer disease (AD). Their relationship with cognition in the earliest stages of AD is unknown. OBJECTIVE: To assess the relationship between WMLs and cognition in nondemented aging and in early-stage AD. DESIGN: Cross-sectional study. SETTING: Alzheimer Disease Research Center, St Louis, MO. PARTICIPANTS: Participants were nondemented (n = 88) or had very mild (n = 48) or mild (n = 20) AD. MAIN OUTCOME MEASURES: Regression coefficients for deep WMLs and periventricular WMLs (PVWMLs) as predictors of cognition, after controlling for age, educational achievement, brain atrophy, and infarctlike lesions. RESULTS: White matter lesions were present in nondemented aging and in early-stage AD, with no group differences in deep WML burden and a modest PVWML burden increase in the AD group. The prevalence of infarctlike lesions was equivalent between groups. Age and hypertension were related to deep WML burden and PVWML burden. Deep WML burden and PVWML burden were associated with reduced global cognition in AD but not in nondemented aging. A PVWML x AD status interaction for global cognition suggests that the relationship between PVWMLs and cognition is modified by AD. In AD, global cognitive reductions were related to impairments in visual memory, processing speed, and executive function. CONCLUSIONS: White matter lesions are prevalent in nondemented aging and in early-stage AD, and their presence influences cognitive impairment in the earliest stages of AD. Individuals with early-stage AD may be more vulnerable to the cognitive effect of WMLs than nondemented aging individuals with similar WML burden.","Age of Onset;Aged;Aged, 80 and over;Aging/*pathology/psychology;Alzheimer Disease/epidemiology/*pathology/psychology;Brain/*pathology/physiopathology;Cognition Disorders/epidemiology/*pathology/psychology;Cross-Sectional Studies;Diagnosis, Differential;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/*pathology;Neuropsychological Tests;Plaque, Amyloid/pathology;Predictive Value of Tests;Prevalence","Burns, J. M.;Church, J. A.;Johnson, D. K.;Xiong, C.;Marcus, D.;Fotenos, A. F.;Snyder, A. Z.;Morris, J. C.;Buckner, R. L.",2005,Dec,10.1001/archneur.62.12.1870,0,
5162,Sex differences in the development of mild cognitive impairment and probable Alzheimer's disease as predicted by the hippocampal volume or white matter hyperintensities,"This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300-0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012-19.08]; HR = 4.665, 95% CI [1.072-20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166-0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011-1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.",Alzheimer disease;brain;disease progression;hippocampus;magnetic resonance imaging;men;sex characteristics;white matter hyperintensities;women,"Burke, S. L.;Hu, T.;Fava, N. M.;Li, T.;Rodriguez, M. J.;Schuldiner, K. L.;Burgess, A.;Laird, A.",2018,Jan 10,,0,
5163,Imaging markers of structural and functional brain changes that precede cognitive symptoms in risk for Alzheimer's disease,"Neuroimaging has rapidly advanced investigations into dysfunction both within and emanating from the hippocampus in early Alzheimer's disease. Focusing on prodromal subjects, we will discuss structural changes to hippocampal subregions, alterations to functional activity both within the hippocampus and elsewhere in the cortex, as well as changes to structural white matter connectivity and changes to functionally correlated patterns during memory performance. We present ample evidence that asymptomatic subjects demonstrate substantial identifiable brain changes before the onset of cognitive decline, but suggest there is significant work yet to be accomplished before applying these findings to individual patients. © 2013 Springer Science+Business Media New York.",,"Burggren, A.;Brown, J.",2014,June,,0,
5164,Optimal Reference Region to Measure Longitudinal Amyloid-beta Change with (18)F-Florbetaben PET,"Accurate measurement of changes in amyloid-beta (Abeta) deposition over time is important in longitudinal studies, particularly in anti-Abeta therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Abeta PET measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Abeta changes using (18)F-florbetaben PET. Methods: Forty-five patients with mild cognitive impairment (mean age +/- SD, 72.69 +/- 6.54 y; 29 men/16 women) who underwent up to 3 (18)F-florbetaben scans were included. Baseline scans were visually classified as high (Abeta+) or low (Abeta-) amyloid. Six cortical regions were quantified using a standardized region-of-interest atlas applied to the spatially normalized gray matter image obtained from segmentation of the baseline T1-weighted volumetric MRI. Four RRs (cerebellar gray matter [CGM], whole cerebellum [WCER], pons, and subcortical white matter [SWM]) were studied. The SUV ratio (SUVR) for each RR was calculated by dividing cortex activity by RR activity, with a composite SUVR averaged over 6 cortical regions. SUVR increase from baseline to 1 and 2 y, and percentage Abeta deposition per year, were assessed across Abeta+ and Abeta- groups. Results: SUVs for any RR were not significantly different over time. Percentage Abeta accumulation per year derived from composite SUVR was 0.10 +/- 1.72 (Abeta-) and 1.36 +/- 1.98 (Abeta+) (P = 0.02) for CGM and 0.13 +/- 1.47 and 1.32 +/- 1.75 (P = 0.01), respectively, for WCER. Compared with baseline, the composite SUVR increase in Abeta+ scans was significantly larger than in Abeta- scans at 1 y (P = 0.04 [CGM]; P = 0.03 [WCER]) and 2 y (P = 0.02 [CGM]; P = 0.01 [WCER]) using these 2 RRs. Significant SUVR changes using the pons as the RR were detected only at 2 y (P = 0.46 [1 y], P = 0.001 [2 y]). SUVR using the SWM as the RR showed no significant differences at either follow-up (P = 0.39 [1 y], P = 0.09 [2 y]). Conclusion: RR selection influences reliable early measurement of Abeta changes over time. Compared with SWM and pons, which do not fulfil the RR requirements and have limited sensitivity to detect Abeta changes, cerebellar RRs are recommended for (18)F-florbetaben PET because they allow earlier detection of Abeta accumulation.",0 (4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene);0 (Amyloid beta-Peptides);0 (Aniline Compounds);0 (Stilbenes);Aged;Alzheimer Disease/diagnostic imaging/metabolism;Amyloid beta-Peptides/ metabolism;Aniline Compounds/metabolism;Biological Transport;Female;Humans;Longitudinal Studies;Male;Positron-Emission Tomography/ standards;Reference Standards;Stilbenes/metabolism;amyloid beta;florbetaben PET;longitudinal;reference region,"Bullich, S.;Villemagne, V. L.;Catafau, A. M.;Jovalekic, A.;Koglin, N.;Rowe, C. C.;De Santi, S.",2017,Aug,,0,
5165,18F-Florbetaben SUVR cutoff quantification across reference regions and standards of truth and comparison to visual assessment,"Background: Thresholds of 18F-florbetaben (FBB) standardized uptake value ratios (SUVRs) to categorize scans as positive or negative between 1.39 (Barthel et al., Lancet Neurol 2011;10:424-35) and 1.48 (Sabri et al., Alzheimers Dement. 2015;11(8):964-74) have been reported using cerebellar grey matter (GCER) as the reference region (RR). The aims of this study were 1) to generate 18F-Florbetaben (FBB) SUVR cutoff values for different reference regions (RRs) using blinded visual assessment (VA) as standard of truth (SoT); 2) to validate them in a different clinical population and SoTs and 3) to compare VA and SUVR cutoffs. Methods: For aim1, SUVR cutoff was generated using FBB scans from 143 subjects (69.5+/-7.5 yrs; n=75 Alzheimer's disease (AD), n=68 healthy volunteers (HVs)) who were visually assessed by 3 readers. SUVR was calculated using cerebellar gray matter (GCER), whole cerebellum (WCER), pons (PONS), and subcortical white matter (SWM) as RRs. A SUVR cutoff value for each RR was generated using Receiver Operating Characteristic analysis, VA as the SoT, and highest Youden's index as the selection criteria. For aim 2, SUVR cutoffs were validated in 78 end-of life subjects (80.1+/-10.4 yrs) using VA from 8 readers and histopathological confirmation of the presence of neuritic beta-amyloid plaques as SoT. For aim 3, FBB scans from 78 subjects were visually assessed by 8 readers. The number of correctly or incorrectly classified scans according to pathology results using VA and SUVR cutoffs for each RR was compared. Results: Aim 1: Composite SUVR cutoffs were 1.43 (GCER); 0.96 (WCER); 0.78 (PONS); 0.71 (SWM). Aim2: Accuracy values were high and consistent across SUVR cutoffs and VA methods and SoTs (range 83-94% for histopathology, and 86-94% for VA). Aim 3: A range of 63-71 cases were correctly classified by both SUVR cutoff (across RRs) and VA, while 1-3 cases (across RRs) were incorrectly classified by both SUVR cutoff and VA. SUVR cutoff method misclassified more cases (range: 3-10 cases) than VA (range: 1-3 cases) for any RR. Conclusion: VA and SUVR cutoff quantification perform similarly in classifying FBB scans. These results indicate that VA is a robust method for the correct classification of FBB scans. However, the use of SUVR cutoff did not improve VA classification of FBB scans independently of the RR used in this end-of-life population.",Alzheimer disease;amyloid plaque;classification;clinical trial;controlled clinical trial;controlled study;gray matter;histopathology;human;major clinical study;pons;quantitative study;receiver operating characteristic;single blind procedure;volunteer;white matter;Youden index;amyloid beta protein;florbetaben,"Bullich, S.;Catafau, A. M.;Seibyl, J.;Barthel, H.;Sabri, O.;Santi, S.",2017,,,0,
5166,Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL),"Objective: To characterize the clinical and MRI features of 2 families with adult-onset dominant leukoencephalopathy and strokes and identify the underlying genetic cause. Methods: We applied MRI pattern recognition, whole-exome sequencing, and neuropathology. Results: Based on brain imaging, 13 family members of 40 years or older from 2 families were diagnosed with the disease; in 11 family members of the same age, MRI was normal. In the affected family members, MRI showed a leukoencephalopathy that was disproportionately severe compared to the clinical disease. The clinical picture was dominated by ischemic and hemorrhagic strokes, slow and late cognitive deterioration, and therapy-resistant hypertension. With whole-exome sequencing, we identified one variant shared by both families and segregating with the disease: c.973C>T in CTSA. Haplotype analysis revealed a shared 1,145-kb interval encompassing the CTSA variant on chromosome 20q13.12, suggesting a common ancestor. Brain autopsy of 3 patients showed a leukoencephalopathy that was disproportionately extensive compared to the vascular abnormalities. CTSA encodes cathepsin A. Recessive CTSA mutations cause galactosialidosis. One of the numerous cathepsin A functions is to degrade endothelin-1. In the patients, striking endothelin-1 immunoreactivity was found in white matter astrocytes, correlating with increased numbers of premyelinating oligodendrocyte progenitors. This finding supports a role for endothelin-1 in the leukoencephalopathy through inhibition of oligodendrocyte progenitor maturation. Conclusions: CARASAL (cathepsin A-related arteriopathy with strokes and leukoencephalopathy) is a novel hereditary adult-onset cerebral small vessel disease. It is of interest that, next to the cerebral vascular abnormalities, endothelin-1 may have a role in the pathogenesis of the extensive leukoencephalopathy.",carboxypeptidase C;endothelin 1;adult;article;astrocyte;autopsy;autosomal dominant disorder;cathepsin A related arteriopathy with stroke and leukoencephalopathy;cerebrovascular accident;chromosome variant;clinical article;controlled study;disease severity;galactosialidosis;gene sequence;haplotype;human;immunoreactivity;leukoencephalopathy;mental deterioration;neuroimaging;neuropathology;nuclear magnetic resonance imaging;oligodendrocyte progenitor;pattern recognition;priority journal;resistant hypertension,"Bugiani, M.;Kevelam, S. H.;Bakels, H. S.;Waisfisz, Q.;Ceuterick-De Groote, C.;Niessen, H. W. M.;Abbink, T. E. M.;Lesnik Oberstein, S. A. M. J.;Van Der Knaap, M. S.",2016,,10.1212/wnl.0000000000003251,0,
5167,Profile of cognitive dysfunction and relation with gait disturbance in Normal Pressure Hydrocephalus,"OBJECTIVES: Although dementia is one of the most relevant symptoms of the idiopathic Normal-Pressure Hydrocephalus (iNPH) syndrome, some doubts remain about the nature of cognitive deficits in this disease. We aimed to determine the neuropsychological profile in iNPH and its relation with ventricular size, white matter vascular lesions (WML) and gait dysfunction. METHODS: Seventeen iNPH patients and a control group (n=14) were assessed with a battery of neuropsychological tests and a timed walk test. We calculated measures of frontal horn, occipital horn and third ventricle sizes and assessed white matter lesion (WML) load with a validated visual scale. RESULTS: Patients differed significantly from controls in all cognitive tests, but did worse on the Rey Complex Figure test. We found no significant correlations between cognitive and imaging results in iNPH. Cognitive function was related to gait in controls, but not in iNPH patients. CONCLUSIONS: Patients presented widespread cognitive dysfunction with a predominance of visuo-spatial deficits. Dissociation between gait and cognitive dysfunction in iNPH patients suggests the existence of different pathophysiological mechanisms.","Aged;Aged, 80 and over;Cerebral Ventricles/pathology;Cognition Disorders/ etiology/ psychology;Executive Function;Female;Gait Disorders, Neurologic/ etiology/ psychology;Humans;Hydrocephalus, Normal Pressure/ complications/ psychology;Immunohistochemistry;Magnetic Resonance Imaging;Male;Middle Aged;Neurologic Examination;Space Perception;Stroop Test;Vision Disorders/etiology/psychology;Wechsler Scales","Bugalho, P.;Alves, L.;Miguel, R.;Ribeiro, O.",2014,Mar,10.1016/j.clineuro.2014.01.006,0,
5168,Lobar Dementia due to Extreme Widening of Virchow-Robin Spaces in One Hemisphere,"Widened perivascular spaces known as Virchow-Robin spaces (VRS) are often seen on MRI and are usually incidental findings. It is unclear if enlarged VRS can be associated with neurological deficits. In this report, we describe a case of lobar dementia associated with unusual VRS widening in one cerebral hemisphere. A 77-year-old woman, seen at a memory clinic, presented with progressive cognitive decline, left hemianopsia, and mild pyramidal signs on the left side. On MRI, unusually wide VRS were visible, predominantly in the right centrum semiovale and the right temporo-occipital white matter. The clinical syndrome was consistent with the extent and location of the abnormally dilated VRS. The high MR signal in white matter bridges between the VRS suggested parenchymal damage, possibly representing gliotic white matter. No evidence for another etiology was found on cerebral MRI and rCBF SPECT. As a conclusion, enlarged VRS in one cerebral hemisphere may be associated with cognitive change and neurological deficits.",,"Buerge, C.;Steiger, G.;Kneifel, S.;Wetzel, S.;Wollmer, M. A.;Probst, A.;Baumann, T. P.",2011,May,10.1159/000329267,0,
5169,Structural and functional papez circuit integrity in amyotrophic lateral sclerosis,"Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit-a circuit known to participate in memory processes-is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established.",Amyotrophic lateral sclerosis;Cognitive deficits;Episodic memory;Multimodal MRI;Papez circuit,"Bueno, A. P. A.;Pinaya, W. H. L.;Moura, L. M.;Bertoux, M.;Radakovic, R.;Kiernan, M. C.;Teixeira, A. L.;de Souza, L. C.;Hornberger, M.;Sato, J. R.",2018,Jan 27,,0,
5170,"25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services","BACKGROUND: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). METHODS: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65-99 years) from 2003 to 2007. RESULTS: Among 318 participants, the mean age was 73.5 +/- 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10-20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (< or =20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (< or =20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1-6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.","Aged;Aged, 80 and over;Alzheimer Disease/*etiology;Body Mass Index;Confidence Intervals;Cross-Sectional Studies;Dementia/classification/*etiology;Female;Humans;Logistic Models;Magnetic Resonance Imaging/methods;Male;Neurologic Examination/methods;Odds Ratio;Phlebotomy/methods;Retrospective Studies;Risk Factors;Stroke/*etiology;Temporal Lobe/pathology;Vitamin D/*analogs & derivatives/blood;Vitamin D Deficiency/*complications","Buell, J. S.;Dawson-Hughes, B.;Scott, T. M.;Weiner, D. E.;Dallal, G. E.;Qui, W. Q.;Bergethon, P.;Rosenberg, I. H.;Folstein, M. F.;Patz, S.;Bhadelia, R. A.;Tucker, K. L.",2010,Jan 5,10.1212/WNL.0b013e3181beecb7,0,
5171,Novel mutation of the NOTCH3 gene in a Polish family with CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small blood vessels disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH 3). We present a Polish family with a previously unreported novel mutation in exon 12 c.1851C>C/G of the NOTCH3 gene and varying disease expression. One of the two family members with the confirmed mutation presented with all the main CADASIL symptoms; while, his affected father was nearly asymptomatic. Both family members had epilepsy, coronary artery disease, and abdominal aorta aneurysm. Our observation confirms there is phenotypic variability in CADASIL not only between, but also within, families carrying the same mutation.",cysteine;Notch3 receptor;tryptophan;abdominal aorta aneurysm;adult;aged;aneurysm rupture;article;atrial septal aneurysm;brain ischemia;CADASIL;clinical article;cognition;coronary artery disease;depression;disease severity;epilepsy;genetic screening;heart aneurysm;heart ejection fraction;heart failure;human;Huntington chorea;male;middle aged;missense mutation;neuroimaging;nuclear magnetic resonance imaging;Polish citizen;post infarction heart failure;skin blood vessel;very elderly;white matter,"Buczek, J.;Błażejewska-Hyżorek, B.;Cudna, A.;Lusawa, M.;Lewandowska, E.;Kurkowska-Jastrzębska, I.;Członkowska, A.",2016,,,0,
5172,Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection,"HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.","AIDS Dementia;Complex/blood/ diagnosis/etiology/pathology/physiopathology/virology;Animals;Asymptomatic Diseases;Body Weight;Brain/ pathology/physiopathology/virology;Cats;Diffusion Magnetic Resonance Imaging/ methods;Feline Acquired Immunodeficiency;Syndrome/blood/complications/ diagnosis/pathology/physiopathology/virology;Immunodeficiency Virus, Feline/physiology;Immunohistochemistry;Lymphocyte Count;Magnetic Resonance Spectroscopy/ methods;Mitogen-Activated Protein Kinase Kinases/analysis;Species Specificity;Viral Load/physiology","Bucy, D. S.;Brown, M. S.;Bielefeldt-Ohmann, H.;Thompson, J.;Bachand, A. M.;Morges, M.;Elder, J. H.;Vandewoude, S.;Kraft, S. L.",2011,Aug,10.1007/s13365-011-0040-7,0,
5173,"Conversion of aMCI subjects to AD in relation to flutemetamol Amyloid status, white matter hyper-intensities and hippocampal volume in a phase III longitudinal study","Introduction Previously, GE Healthcare conducted a three-year outcome study in which 232 patients with amnestic mild cognitive impairment (aMCI) underwent baseline amyloid PET imaging with [<sup>18</sup>F]flutemetamol to determine time to conversion to dementia in relation to baseline amyloid status. Conversion was determined by an independent clinical adjudication committee, which reviewed the results of 6-monthly neuropsychiatric testing for up to 36 months. While amyloid positivity was a significant and independent predictor of conversion, a fraction (23%) of the amyloid-negative subjects also converted while 77% did not convert in the three year study window. In this post-hoc analysis, we determined the association of hippocampal atrophy and whitematter lesion load with conversion to dementia with the ultimate aim of improving conversion prediction. Methods Baseline MRI scans from the study cohort were analysed quantitatively for hippocampal volume and white-matter lesion load in a post-hoc analysis. ANOVA was used to compare hippocampal volume by conversion to dementia status and amyloid status by dichotomous [<sup>18</sup>F]flutemetamol PET image visual read. A similarmodel included whitematter lesion load as the dependent variable. Results Among amyloid-negative patients, converters had both a significantly higher white matter lesion load (p=0.0033) and a significantly lower hippocampal volume (p<0.0001) than non-converters. For amyloid-positive patients, converters had a significantly lower hippocampal volume than non-converters (p=0.0140) but the difference between converters and non-converters in white-matter load was not statistically significant. Discussion Subjects who are amyloid-negative by [<sup>18</sup>F]flutemetamol at baseline are less likely to progress in the short term to dementia than those with a positive scan. The results above provide evidence that amyloid-negative aMCI subjects who converted to dementia had significant levels of either a white-matter lesion load or hippocampal atrophy as compared to the amyloid-negative non-converters. This presentation elucidates the relationship between the assessment of amyloid PET and MRI biomarkers which can be combined to predict conversion from aMCI to symptomatic dementia.",analysis of variance;atrophy;controlled clinical trial;controlled study;dementia;dependent variable;disease course;doctor patient relation;hippocampus;human;longitudinal study;major clinical study;mild cognitive impairment;nuclear magnetic resonance imaging;phase 3 clinical trial;positron emission tomography;post hoc analysis;prediction;quantitative study;white matter lesion,"Buckley, C. J.;Zanette, M.;Cherubini, A.",2017,,,0,
5174,Dementia of the Alzheimer type and multi-infarct dementia: A clinical description and diagnostic problems,"Patients who had Alzheimer's disease - senile dementia of the Alzheimer type (AD/SDAT) or multi-infarct dementia (MID) were compared with a group of controls. Demented patients had approximately the same degree of dementia and the same duration of illness. The MID group had a significantly higher mean age than the AD/SDAT group. Sixty-three per cent of the AD/SDAT patients were free of other diseases, while 65 per cent of the MID patients had cardiovascular disease. Thirty per cent of the MID patients had a history of previous depression, while only 5 per cent of the AD/SDAT patients had had depression. At the time of the investigation, however, AD/SDAT patients showed significantly more signs of depression than the MID patients. Focal neurologic signs were found in 70 per cent of the MID patients and only 6 per cent of the AD/SDAT patients. The electrocardiogram was normal for every AD/SDAT patient, while 75 per cent of the MID patients had abnormal ECGs. Electroencephalography showed generalized slow frequencies in 79 per cent of the AD/SDAT patients and localized slow frequencies and abnormalities in 65 per cent of the MID patients. Computed tomography of the brain showed that MID patients had significantly greater dilation of the ventricular system, while cortical atrophy did not differ significantly among the three groups. Homovanillic acid in the cerebrospinal fluid was significantly lower in the AD/SDAT group as compared with controls.",Alzheimer disease;autopsy;central nervous system;dementia;diagnosis;etiology;histology;human;major clinical study;multiinfarct dementia;psychological aspect,"Bucht, G.;Adolfsson, R.;Winblad, B.",1984,,,0,
5175,Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis,"Background To investigate white matter structural connectivity changes associated with amyotrophic lateral sclerosis (ALS) using network analysis and compare the results with those obtained using standard voxel-based methods, specifically Tract-based Spatial Statistics (TBSS). Methods MRI data were acquired from 30 patients with ALS and 30 age-matched healthy controls. For each subject, 85 grey matter regions (network nodes) were identified from high resolution structural MRI, and network connections formed from the white matter tracts generated by diffusion MRI and probabilistic tractography. Whole-brain networks were constructed using strong constraints on anatomical plausibility and a weighting reflecting tract-averaged fractional anisotropy (FA). Results Analysis using Network-based Statistics (NBS), without a priori selected regions, identified an impaired motor-frontal-subcortical subnetwork (10 nodes and 12 bidirectional connections), consistent with upper motor neuron pathology, in the ALS group compared with the controls (P=0.020). Reduced FA in three of the impaired network connections, which involved fibers of the corticospinal tract, correlated with rate of disease progression (P≤0.024). A novel network-tract comparison revealed that the connections involved in the affected network had a strong correspondence (mean overlap of 86.2%) with white matter tracts identified as having reduced FA compared with the control group using TBSS. Conclusion These findings suggest that white matter degeneration in ALS is strongly linked to the motor cortex, and that impaired structural networks identified using NBS have a strong correspondence to affected white matter tracts identified using more conventional voxel-based methods. J. Magn. Reson. Imaging 2015;41:1342-1352.",,"Buchanan, C. R.;Pettit, L. D.;Storkey, A. J.;Abrahams, S.;Bastin, M. E.",2015,1,,0,
5176,A voxel-based morphometry comparison of the 3.0T ADNI-1 and ADNI-2 volumetric MRI protocols,"Objectives The Alzheimer's Disease Neuroimaging Initiative 3.0T MRI image acquisition scheme changed between the original ADNI-1 grant and the two subsequent grants (ADNI-GO and ADNI-2). The aim of the current study was to investigate the compatibility of the 3.0T ADNI-1 and ADNI-2 T1-weighted volumes using voxel-based morphometry (VBM). Methods T1-weighted images of 30 subjects were acquired using a 3T GE Signa HDx using the ADNI-1 and ADNI-2 T1-weighted volume sequences. Images were pre-processed and analysed using SPM8. Global grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) volumes were compared, as well as voxel-by-voxel differences in",,"Brunton, S.;Gunasinghe, C.;Jones, N.;Kempton, M. J.;Westman, E.;Simmons, A.",2014,1,,0,
5177,"A severe case of Dentatorubro-pallidoluysian atrophy (DRPLA) with microcephaly, very early onset of seizures, and cerebral white matter involvement","We report a severe case of Dentatorubro-pallidoluysian atrophy (DRPLA) presenting with microcephaly, developmental delay, severe epilepsy, and progressive mental deterioration with a very early onset of disease. The case is notable for the early detection of white matter changes by brain MRI. Neuroradiological findings from the case were compared to those of previously reported patients with disease onset before 10 years of age. © Georg Thieme Verlag KG Stuttgart.",licarbazepine;phenytoin;topiramate;zonisamide;anamnesis;article;case report;clinical feature;dentatorubropallidoluysian atrophy;disease severity;early diagnosis;electroencephalogram;human;male;mental deterioration;microcephaly;neuroimaging;nuclear magnetic resonance imaging;priority journal;radiodiagnosis;school child;seizure;white matter,"Brunetti-Pierri, N.;Wilfong, A. A.;Hunter, J. V.;Craigen, W. J.",2006,,,0,
5178,Measurement of global brain atrophy in Alzheimer's disease with unsupervised segmentation of spin-echo MRI studies,"In 16 patients with probable Alzheimer's disease (AD; NINDS criteria, age range 56-78 years), gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) absolute and fractional volumes were measured with an unsupervised multiparametric post-processing segmentation method based on estimates of relaxation rates R1, R2 (R1 = 1/T1; R2 = 1/T2) and proton density [N(H)] from conventional spin-echo studies (Alfano et al. Magn. Reson. Med. 1997;37:84-93). Global brain atrophy, and GM and WM fractions significantly correlated with Mini-Mental Status Examination and Blessed Dementia Scale scores. Compared with normals, brain compartments in AD patients showed decreased GM (-6.84 +/- 1.58%) and WM fractions (-9.79 +/- 2.47%) and increased CSF fractions (+58.80 +/- 10.37%). Changes were more evident in early-onset AD patients. In AD, measurement of global brain atrophy obtained by a computerized procedure based on routine magnetic resonance studies could complement the information provided by neuropsychological tests for the assessment of disease severity.","Aged;Alzheimer Disease/*diagnosis;Atrophy;Brain/*pathology;Cerebral Ventricles/pathology;*Echo-Planar Imaging;Female;Humans;Image Interpretation, Computer-Assisted;*Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Neuropsychological Tests","Brunetti, A.;Postiglione, A.;Tedeschi, E.;Ciarmiello, A.;Quarantelli, M.;Covelli, E. M.;Milan, G.;Larobina, M.;Soricelli, A.;Sodano, A.;Alfano, B.",2000,Mar,,0,
5179,Cerebral microbleeds are not associated with long-term cognitive outcome in patients with transient ischemic attack or minor stroke,"Background: Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. Methods: Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n = 397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n = 280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n = 48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. Results: The mean age was 65 ± 12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70 ± 9 vs. 64 ± 12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p < 0.05). The mean TICS score was 35.3 ± 5.9 for patients with microbleeds (n = 29) and 34.6 ± 5.2 for patients without microbleeds (n = 251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0 ± 10.8 for patients with microbleeds (n = 9) and 63.1 ± 12.9 for patients without microbleeds (n = 39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient β: -0.12 (-0.23 to 0.00); p = 0.04] and with lower IQCODE score [0.51 (0.19-0.83); p = 0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p = 0.01). Conclusions: In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease. © 2014 S. Karger AG, Basel.",,"Brundel, M.;Kwa, V. I. H.;Bouvy, W. H.;Algra, A.;Kappelle, L. J.;Biessels, G. J.",2014,March,,0,
5180,Brain imaging in type 2 diabetes,"Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and dementia. Brain imaging may provide important clues about underlying processes. This review focuses on the relationship between T2DM and brain abnormalities assessed with different imaging techniques: both structural and functional magnetic resonance imaging (MRI), including diffusion tensor imaging and magnetic resonance spectroscopy, as well as positron emission tomography and single-photon emission computed tomography. Compared to people without diabetes, people with T2DM show slightly more global brain atrophy, which increases gradually over time compared with normal aging. Moreover, vascular lesions are seen more often, particularly lacunar infarcts. The association between T2DM and white matter hyperintensities and microbleeds is less clear. T2DM has been related to diminished cerebral blood flow and cerebrovascular reactivity, particularly in more advanced disease. Diffusion tensor imaging is a promising technique with respect to subtle white matter involvement. Thus, brain imaging studies show that T2DM is associated with both degenerative and vascular brain damage, which develops slowly over the course of many years. The challenge for future studies will be to further unravel the etiology of brain damage in T2DM, and to identify subgroups of patients that will develop distinct progressive brain damage and cognitive decline.","Atrophy/pathology;Brain/ pathology;Cerebrovascular Circulation/physiology;Cerebrovascular Disorders/complications/ pathology;Diabetes Mellitus, Type 2/complications/ pathology/physiopathology;Diffusion Tensor Imaging;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Neuroimaging;Tomography, Emission-Computed, Single-Photon","Brundel, M.;Kappelle, L. J.;Biessels, G. J.",2014,Dec,10.1016/j.euroneuro.2014.01.023,0,
5181,High prevalence of cerebral microbleeds at 7Tesla MRI in patients with early Alzheimer's disease,"The prevalence of microbleeds on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD) is lower than that of its presumed pathological correlate, cerebral amyloid angiopathy. We examined 18 patients with early AD or mild cognitive impairment (MCI) and 18 non-demented controls with ultra-high field strength 7Tesla MRI, to assess if the actual prevalence of microbleeds could be higher than is currently reported. One or more microbleeds were visualized in 78% of the MCI/AD patients and in 44% of the controls (p = 0.04). 7Tesla MRI shows that presence of microbleeds may be the rule, rather than exception in patients with MCI/AD.","Alzheimer Disease [diagnosis] [epidemiology] [physiopathology];Cerebral Hemorrhage [diagnosis] [epidemiology] [physiopathology];Early Diagnosis;Echo-Planar Imaging [methods];Microcirculation [physiology];Prevalence;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword]","Brundel, M.;Heringa, S. M.;Bresser, J.;Koek, H. L.;Zwanenburg, J. J.;Jaap Kappelle, L.;Luijten, P. R.;Biessels, G. J.",2012,,10.3233/jad-2012-120364,0,
5182,Brain changes in dementia of Alzheimer's type relevant to new imaging diagnostic methods,"The aim of the article is to correlate grey and white matter changes and their topography to the results of modern methods for brain imaging such as CT, rCBF, PET, SPECT and NMR in Alzheimer's type of dementia. The findings are based on the study of a large material investigated thoroughly patho-anatomically. The findings are correlated with psychiatric and neurophysiologic follow-up studies. The degenerative grey matter process shows a regionally varying accent according to a pattern which is consistent and typical for the disease. This corresponds to metabolic changes on rCBF, PET and SPECT and thereby becomes of diagnostic value. This pattern is largely symmetric. Metabolic asymmetries have however been reported on PET scans. In this context individual variations of the topographic degenerative brain pattern and normal anatomical brain asymmetries are of interest. The white matter however also frequently shows changes, in particular loss of myelin and axons and a mild gliosis, slight in 1/3 of the cases and severe in an additional 1/3. These changes cause a decrease of density in the centrum semiovale correlating to lipid depletion. They may also influence the ventricular shape and size, of interest in CT or NMR studies. Also here variations in ventricular shape, normal and such due to pathological processes unrelated to the Alzheimer disease, may cause confusion, regarding degree of atrophy and even type of brain process. Such factors should be considered in the interpretation of non-invasive brain studies.","Aging;Alzheimer Disease/ pathology;Atrophy;Brain/ pathology;Humans;Lipids/analysis;Magnetic Resonance Spectroscopy;Myelin Sheath/analysis;Tomography, Emission-Computed;Tomography, X-Ray Computed","Brun, A.;Englund, E.",1986,,,0,
5183,Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project,"OBJECTIVES: To describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimer's disease (AD). DESIGN: Cross-sectional observational study. SETTING: All scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if >/=2. PARTICIPANTS: 575 participants (45-75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (>/=26), Memory Impairment Screen (>/=6), Time Orientation Subtest of the Barcelona Test II (>/=68), verbal semantic fluency (naming animals >/=12). Clinical Dementia Rating (CDR) had to be 0. RESULTS: 155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD. CONCLUSIONS: Brain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants. TRIAL REGISTRATION NUMBER: NCT02198586.",Alzheimer's disease;cerebral MRI;healthy;incidental finding;late middle-aged;prevention,"Brugulat-Serrat, A.;Rojas, S.;Bargallo, N.;Conesa, G.;Minguillon, C.;Fauria, K.;Gramunt, N.;Molinuevo, J. L.;Gispert, J. D.",2017,Mar 24,,0,
5184,[Imagery of human immunodeficiency virus (HIV) encephalitis] Imagerie des encephalites du virus de l'immunodeficience humaine (V.I.H.),"The authors present the different aspects of HIV encephalitis in CT and MR in a series of 15 patients with anatomopathological proof. Atrophy was the most commonly found lesion (12 patients) and could rapidly be evolutive. White matter lesions (9 patients) were more of ten nodular than diffuse. They were better demonstrated by MRI and did not enhance after intra-venous injection of DOTA-gadolinium. A frequent association with opportunistic infections (toxoplasmosis: 10 patients, CMV:2 patients), lymphoma (4 patients), or PML (3 patients) was observed which emphasized the low specificity of brain imaging in patients with HIV encephalitis.","0 (Contrast Media);0 (Heterocyclic Compounds);0 (Organometallic Compounds);99J2XUF1JT (gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate);AU0V1LM3JT (Gadolinium);AIDS Dementia Complex/ diagnosis/diagnostic imaging;AIDS-Related Opportunistic Infections/diagnosis/diagnostic imaging;Adult;Atrophy;Brain Neoplasms/diagnosis/diagnostic imaging;Contrast Media;Cytomegalovirus Infections/diagnosis/diagnostic imaging;Encephalitis, Viral/ diagnosis/diagnostic imaging;Female;Gadolinium;Heterocyclic Compounds;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/diagnostic imaging;Lymphoma, AIDS-Related/diagnosis/diagnostic imaging;Magnetic Resonance Imaging;Male;Organometallic Compounds;Tomography, X-Ray Computed;Toxoplasmosis, Cerebral/diagnosis/diagnostic imaging","Brugieres, P.;Combes, C.;Ricolfi, F.;Houhou, S.;Sadik, J. C.;Thomas, P.;Gray, F.;Gaston, A.",1995,Sep,,0,
5185,Imagery of human immunodeficiency virus (HIV) encephalitis,"The authors present the different aspects of HIV encephalitis in CT and MR in a series of 15 patients with anatomopathological proof. Atrophy was the most commonly found lesion (12 patients) and could rapidly be evolutive. White matter lesions (9 patients) were more of ten nodular than diffuse. They were better demonstrated by MRI and did not enhance after intra-venous injection of DOTA-gadolinium. A frequent association with opportunistic infections (toxoplasmosis: 10 patients, CMV:2 patients), lymphoma (4 patients), or PML (3 patients) was observed which emphasized the low specificity of brain imaging in patients with HIV encephalitis.","AIDS Dementia Complex/ diagnosis/radiography;AIDS-Related Opportunistic Infections/diagnosis/radiography;Adult;Atrophy;Brain Neoplasms/diagnosis/radiography;Contrast Media;Cytomegalovirus Infections/diagnosis/radiography;Encephalitis, Viral/ diagnosis/radiography;Female;Gadolinium;Heterocyclic Compounds;Humans;Leukoencephalopathy, Progressive Multifocal/diagnosis/radiography;Lymphoma, AIDS-Related/diagnosis/radiography;Magnetic Resonance Imaging;Male;Organometallic Compounds;Tomography, X-Ray Computed;Toxoplasmosis, Cerebral/diagnosis/radiography","Brugieres, P.;Combes, C.;Ricolfi, F.;Houhou, S.;Sadik, J. C.;Thomas, P.;Gray, F.;Gaston, A.",1995,Sep,,0,
5186,Neuroimaging of Basal Ganglia Calcifications,"Basal ganglia calcifications are a frequent neuroimaging finding upon cerebral computerized tomography (CT) and may incidentally be identified in about 1 % of otherwise normal elderly subjects. The clinical picture of symptomatic basal ganglia calcifications includes neuropsychiatric abnormalities and movement disorders. Idiopathic cases, often referred to as Fahr's disease, idiopathic basal ganglia calcification (IBGC) or bilateral striato-pallido-dentate calcinosis (BSPDC), are either familial, mostly with an autosomal dominant mode of inheritance, or, less commonly, sporadic. Secondary causes such as disorders of calcium metabolism, vascular malformations, phacomatoses, tumors, or parasitical infections of the central nervous system may also lead to intracranial mineralization deposits. Apart from the basal ganglia (striatum and pallidum), a variety of anatomical structures can be affected by calcification, including the dentate nucleus, thalamus, and subcortical white matter. Calcifications typically show a symmetric distribution and differ in intensity and localization among affected subjects. Cerebral CT is the diagnostic gold standard to verify intracerebral calcifications. In contrast, magnetic resonance imaging (MRI) appears to have a rather low sensitivity and specificity and often MRI results remain inconclusive. Recently, transcranial sonography was consistently shown to reveal symmetric hyperechogenic areas of the basal ganglia corresponding to mineralization in patients with BSPDC. However, systemic investigations on the diagnostic value are lacking. Functional radioligand imaging methods provide an opportunity to demonstrate changes in the nigrostriatal function, local brain perfusion, and glucose metabolism. This chapter aims to clarify the heterogeneous terminology of basal ganglia calcifications and addresses the etiology and diagnostic approaches. Assets and drawbacks of different diagnostic tools are discussed.",,"Brüggemann, N.;Hagenah, J.",2013,2013,,0,
5187,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance,"BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathic syndrome related to a genetic defect on chromosome 19. Characteristic changes in CADASIL can be observed onT2-weighted MR images in the subcortical white matter. The purpose of this study was to measure changes of regional cerebral blood volume (rCBV) with dynamic contrast-enhanced MR imaging and to correlate the changes to disability and cognitive performance. METHODS: We obtained rCBV measurements of 24 individuals with proven CADASIL on a 1.5-T MR imaging unit. A susceptibility-weighted MR imaging sequence was used for bolus tracking. Principles of the indicator dilution theory were applied to estimate values of absolute rCBV (mL/100 g). Disability was determined by using the Rankin scale, and overall cognitive performance was assessed by using the Mini-Mental State Examination. RESULTS: The mean rCBV in the subcortical white matter that was hyperintense on the T2-weighted images (2.7 +/- 0.8 mL/100 g) was significantly lower than the rCBV in the white matter that appeared normal on the T2-weighted images (4.4 +/- 1.3 mL/100 g) (P <.05). The mean rCBV in the gray matter was within the normal range (8.3 +/- 1.7 mL/100 g). Both cognitive impairment and disability negatively correlated with rCBV in the subcortical white matter that was hyperintense (P <.05) but not with rCBV in the normal appearing white matter. rCBV did not correlate with age. CONCLUSION: rCBV measured in the hyperintense subcortical white matter in individuals with CADASIL was decreased and inversely correlated with disability and cognitive impairment.","Adult;Aged;Blood Volume/physiology;Brain/blood supply;Cerebral Arterial Diseases/diagnosis/ genetics;Cerebral Infarction/diagnosis/ genetics;Chromosome Aberrations/ genetics;Chromosome Disorders;Dementia/diagnosis/ genetics;Dementia, Vascular/diagnosis/ genetics;Disability Evaluation;Dominance, Cerebral/physiology;Female;Genes, Dominant/ genetics;Humans;Image Processing, Computer-Assisted;Male;Mental Status Schedule;Middle Aged;Neurologic Examination;Regional Blood Flow/physiology;Syndrome","Bruening, R.;Dichgans, M.;Berchtenbreiter, C.;Yousry, T.;Seelos, K. C.;Wu, R. H.;Mayer, M.;Brix, G.;Reiser, M.",2001,Aug,,0,
5188,"Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well","We investigated capillary density in 12 subjects with leukoaraiosis (LA), in 9 age-matched normal subjects, in 7 cases of Alzheimer's disease (AD), and 4 after whole-brain irradiation for brain tumors. In the LA study (which as been published), autopsy brains were evaluated by MRI. The presence of LA was indicated by confluent or patchy areas of hyperintensity in the deep white matter. We employed a stereology method using computerized image processing and analysis to determine microvascular density. Afferent vessels (arterioles and capillaries, but not veins or venules) were stained for alkaline phosphatase in 100 microm thick celloidin sections. Microvascular density in LA lesions in the deep white matter (2.56%) was significantly lower than in the corresponding deep white matter of normal subjects (3.20%, p=0.0180). LA subjects demonstrated decreased vascular density at early ages (55-65 years) when compared to normal subjects. Our findings indicate that LA affects the brain globally, with capillary loss, although the parenchymal damage is found primarily in the deep white matter. In ongoing studies of the deep white matter in AD brains, we found a pattern of decreased vascular density compared to normal, as well as an age-related decline. In the four irradiated brains, we found very low vessel densities, similar to those found in LA, without an additional age-related decline.","Adult;Aged;Aging/pathology;Alkaline Phosphatase;Biomarkers;Brain Ischemia/ pathology/physiopathology;Capillaries/ pathology;Cerebral Arteries/pathology/physiopathology;Cerebral Cortex/blood supply/ pathology/physiopathology;Coloring Agents;Dementia, Vascular/etiology/ pathology/physiopathology;Female;Humans;Image Processing, Computer-Assisted;Leukoaraiosis/ pathology/physiopathology;Male;Nerve Fibers, Myelinated/ pathology","Brown, W. R.;Moody, D. M.;Thore, C. R.;Challa, V. R.;Anstrom, J. A.",2007,Jun 15,10.1016/j.jns.2007.01.015,0,
5189,An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis,"In established multiple sclerosis, tissue abnormality - as assessed using magnetization transfer ratio - increases close to the lateral ventricles. We aimed to determine whether or not (i) these changes are present from the earliest clinical stages of multiple sclerosis; (ii) they occur independent of white matter lesions; and (iii) they are associated with subsequent conversion to clinically definite multiple sclerosis and disability. Seventy-one subjects had MRI scanning a median of 4.6 months after a clinically isolated optic neuritis (49 females, mean age 33.5 years) and were followed up clinically 2 and 5 years later. Thirty-seven healthy controls (25 females, mean age 34.4 years) were also scanned. In normal-appearing white matter, magnetization transfer ratio gradients were measured 1-5 mm and 6-10 mm from the lateral ventricles. In control subjects, magnetization transfer ratio was highest adjacent to the ventricles and decreased with distance from them; in optic neuritis, normal-appearing white matter magnetization transfer ratio was lowest adjacent to the ventricles, increased over the first 5 mm, and then paralleled control values. The magnetization transfer ratio gradient over 1-5 mm differed significantly between the optic neuritis and control groups [+ 0.059 percentage units/mm (pu/mm) versus -0.033 pu/mm, P = 0.010], and was significantly steeper in those developing clinically definite multiple sclerosis within 2 years compared to those who did not (0.132 pu/mm versus 0.016 pu/mm, P = 0.020). In multivariate binary logistic regression the magnetization transfer ratio gradient was independently associated with the development of clinically definite multiple sclerosis within 2 years (magnetization transfer ratio gradient odds ratio 61.708, P = 0.023; presence of T2 lesions odds ratio 8.500, P = 0.071). At 5 years, lesional measures overtook magnetization transfer ratio gradients as significant predictors of conversion to multiple sclerosis. The magnetization transfer ratio gradient was not significantly affected by the presence of brain lesions [T2 lesions (P = 0.918), periventricular T2 lesions (P = 0.580) or gadolinium-enhancing T1 lesions (P = 0.724)]. The magnetization transfer ratio gradient also correlated with Expanded Disability Status Scale score 5 years later (Spearman r = 0.313, P = 0.027). An abnormal periventricular magnetization transfer ratio gradient occurs early in multiple sclerosis, is clinically relevant, and may arise from one or more mechanisms that are at least partly independent of lesion formation.",gadolinium;adult;article;brain lateral ventricle;contrast enhancement;controlled study;disability;Expanded Disability Status Scale;female;human;image analysis;image processing;major clinical study;male;multiple sclerosis;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;optic neuritis;priority journal;white matter;white matter lesion;1.5T GE Signa Echospeed,"Brown, J. W. L.;Pardini, M.;Brownlee, W. J.;Fernando, K.;Samson, R. S.;Carrasco, F. P.;Ourselin, S.;Gandini Wheeler-Kingshott, C. A. M.;Miller, D. H.;Chard, D. T.",2017,,10.1093/brain/aww296,0,
5190,Brain network local interconnectivity loss in aging APOE-4 allele carriers,"Old age and possession of the APOE-4 allele are the two main risk factors for developing later onset Alzheimer's Disease (AD). Carriers of the APOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imaging (DTI), T1 structural imaging, and cognitive testing on aging APOE-4 noncarriers (n = 30; mean age = 63.8+/-8.3) and APOE-4 carriers (n = 25; mean age = 60.8 +/-9.7). Fiber tractography was used to derive whole brain structural graphs, and graph theory was applied to assess structural network properties. Network communication efficiency was determined for each network by quantifying local interconnectivity, global integration, and the balance between these, the small worldness. Relative to noncarriers, APOE-4 carriers demonstrated an accelerated age-related loss of mean local interconnectivity (r = -0.64, P </= 0.01) and regional local interconnectivity decreases in the precuneus (r = -0.64), medial orbitofrontal cortex (r = -0.5), and lateral parietal cortex (r = -0.54). APOE-4 carriers also showed significant age-related loss in mean cortical thickness (r = -0.52, P < 0.05). Cognitively, APOE-4 carriers had significant negative correlations of age and performance on two episodic memory tasks (P < 0.05). This genotype-specific pattern of structural connectivity change with age thus appears related to changes in gross cortical structure and cognition, potentially affecting the rate and/or spatial distribution of AD-related pathology.",Adult;Aged;Aging;Alleles;Apolipoprotein E4/ genetics;Brain/metabolism/ physiology;Brain Mapping/methods;Cognition;Diffusion Tensor Imaging/methods;Female;Genotype;Heterozygote;Humans;Male;Memory;Middle Aged;Risk Factors,"Brown, J. A.;Terashima, K. H.;Burggren, A. C.;Ercoli, L. M.;Miller, K. J.;Small, G. W.;Bookheimer, S. Y.",2011,Dec 20,10.1073/pnas.1109038108,0,
5191,Relation between stage of disease and neurobehavioral measures in children with symptomatic HIV disease,"OBJECTIVE: To study the relationships between stage of HIV disease, reflected by CD4+ lymphocyte percentages and p24 antigen levels, and HIV-associated central nervous system (CNS) abnormalities, measured by computed tomography (CT) brain-scan ratings and neurobehavioral tests. DESIGN: Consecutive case series. SETTING: Government medical research center. PATIENTS: Eighty-six previously untreated children with symptomatic HIV-1 disease. RESULTS: CD4% measures correlated significantly with overall CT brain-scan severity ratings (r = -0.45; P < 0.001) as well as with its component parts (cortical atrophy, white matter abnormalities, and intracerebral calcifications); they were of comparable magnitude for vertically and transfusion-infected children. CD4% measures were also associated with the general level of cognitive function (r = 0.32; P < 0.005). Furthermore, patients with detectable serum p24 antigen levels (n = 39) had CT brain scans that were more abnormal than patients with undetectable p24 levels (n = 20; CT abnormality ratings of 21.3 versus 35.9; P < 0.02); similar differences were found for the cortical atrophy and calcification ratings. p24 levels also correlated with the overall CT brain-scan severity rating (r = 0.34; P < 0.01). CONCLUSIONS: Degree of CT brain-scan abnormality and level of cognitive dysfunction were significantly associated with the stage of HIV-1 disease, as reflected by either CD4 leukocyte measures or elevations of p24 antigen. The relation between the CT brain-scan lesions and markers of HIV disease (both CD4 and p24) suggest that these CNS abnormalities are most likely associated with HIV-1 infection, and further support the hypothesis that the interaction between systemic disease progression and CNS manifestations is continuous rather than discrete.","AIDS Dementia Complex/*diagnosis/physiopathology/radiography;Adolescent;Brain/radiography;CD4 Lymphocyte Count;Child;Child, Preschool;Female;HIV Core Protein p24/analysis;Hiv-1;Humans;Infant;Male;Neuropsychological Tests;Tomography, X-Ray Computed","Brouwers, P.;Tudor-Williams, G.;DeCarli, C.;Moss, H. A.;Wolters, P. L.;Civitello, L. A.;Pizzo, P. A.",1995,Jul,,0,
5192,(1)H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly,"Background and Purpose: White matter hyperintensities in MRI of the brain are often seen in normal elderly subjects. Radiologically, these hyperintense regions are similar to those in symptomatic patients with subcortical arteriosclerotic encephalopathy (SAE). Our aim was to discriminate white matter hyperintensities (WMH) on MRI in patients with SAE from similar appearing changes in normal elderly. Methods: Three groups of elderly patients were studied: symptomatic patients with WMH of SAE (n=5); asymptomatic subjects with diffuse, confluent WMH (n=4); and elderly control subjects (n=5). Proton density images revealed WMH in the occipital lobes. Proton magnetic resonance spectroscopy ((1)HMRS) was used to acquire spectra in these hyperintensities. Metabolite concentrations were calculated from peak areas of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho). Results: The NAA/Cre and NAA/Cho ratios were reduced in the SAE group compared with the two asymptomatic groups (P<.05). NAA was decreased and Cho elevated in SAE compared with control subjects (P<.05). The average volumes of WMH in the SAE group (65.5 cm(3)) and in asymptomatic control subjects (59.4 cm(3)) were similar, and greater than those of the normal control group (4.0 cm(3)). Conclusions: Proton MRS discriminates WMH in SAE patients from those in asymptomatic elderly, suggesting differing causes of the hyperintensities.",,"Brooks, W. M.;Wesley, M. H.;Kodituwakku, P. W.;Garry, P. J.;Rosenberg, G. A.",1997,October,,0,
5193,Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study,"OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes. DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task. SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m(-2)) or obese (>/=30 kg m(-2)). RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight. CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.","Age of Onset;Aged;*Body Mass Index;Brain Mapping;Cluster Analysis;Cognition Disorders/*epidemiology/etiology/*pathology/physiopathology;Female;Frontal Lobe/*pathology/physiopathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Neuroimaging/*methods;Neuropsychological Tests;Obesity/*complications/epidemiology/pathology/physiopathology;Organ Size;Prospective Studies;Sweden/epidemiology","Brooks, S. J.;Benedict, C.;Burgos, J.;Kempton, M. J.;Kullberg, J.;Nordenskjold, R.;Kilander, L.;Nylander, R.;Larsson, E. M.;Johansson, L.;Ahlstrom, H.;Lind, L.;Schioth, H. B.",2013,Feb,10.1038/ijo.2012.13,0,
5194,The Brief Memory and Executive Test (BMET) for detecting vascular cognitive impairment in small vessel disease: a validation study,"BACKGROUND: Cognitive impairment is common in patients with cerebral small vessel disease, but is not well detected using common cognitive screening tests which have been primarily devised for cortical dementias. We developed the Brief Memory and Executive Test (BMET); a rapid screening measure sensitive to the impaired executive function and processing speed characteristic of small vessel disease (SVD). To assess the BMET's validity for general use, we evaluated it when administered by non-psychologists in a multicentre study and collected control data to derive normative scores. METHODS: Two-hundred participants with SVD, defined as a clinical lacunar stroke and a corresponding lacunar infarct on MRI, and 303 healthy controls aged between 40-90 years old were recruited. The BMET, as well as the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE), were performed. Overall, 55 SVD participants underwent repeat testing at 3 months to assess the BMET test-retest reliability. RESULTS: Administering the BMET took a mean (SD) of 12.9 (4.7) in cases and 9.5 (2.6) minutes in controls. Receiver Operator Curve analysis showed the BMET was a good predictor of cognitive impairment in SVD (AUC = 0.94) and performed significantly better than both the MoCA (AUC = 0.77) and the MMSE (AUC = 0.70). Using a cut-off score of 13, the BMET had a sensitivity of 93% and specificity of 76% for detecting cognitive impairment in SVD. CONCLUSIONS: The BMET is a brief and sensitive tool for the detection of cognitive impairment in patients with SVD.","Adult;Aged;Aged, 80 and over;Cognition Disorders/*diagnosis/etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Neuropsychological Tests;Reproducibility of Results;Sensitivity and Specificity;Stroke/*complications/physiopathology","Brookes, R. L.;Hollocks, M. J.;Khan, U.;Morris, R. G.;Markus, H. S.",2015,,10.1186/s12916-015-0290-y,0,
5195,"Depression in small-vessel disease relates to white matter ultrastructural damage, not disability","Objective: To determine whether cerebral small-vessel disease (SVD) is a specific risk factor for depression, whether any association is mediated via white matter damage, and to study the role of depressive symptoms and disability on quality of life (QoL) in this patient group. Methods: Using path analyses in cross-sectional data, we modeled the relationships among depression, disability, and QoL in patients with SVD presenting with radiologically confirmed lacunar stroke (n 5 100), and replicated results in a second SVD cohort (n 5 100). We then compared the same model in a non-SVD stroke cohort (n 5 50) and healthy older adults (n 5 203). In a further study, to determine the role of white matter damage in mediating the association with depression, a subgroup of patients with SVD (n 5 101) underwent diffusion tensor imaging (DTI). Results: Reduced QoL was associated with depression in patients with SVD, but this association was not mediated by disability or cognition; very similar results were found in the replication SVD cohort. In contrast, the non-SVD stroke group and the healthy older adult group showed a direct relationship between disability and depression. The DTI study showed that fractional anisotropy, a marker of white matter damage, was related to depressive symptoms in patients with SVD. Conclusion: These results suggest that in stroke patients without SVD, disability is an important causal factor for depression, whereas in SVD stroke, other factors specific to this stroke subtype have a causal role. White matter damage detected on DTI is one factor that mediates the association between SVD and depression.",,"Brookes, R. L.;Herbert, V.;Lawrence, A. J.;Morris, R. G.;Markus, H. S.",2014,1,,0,
5196,"Neuropsychological, neurological, and MRI correlates of dementia in advanced Huntington's disease: a single case study","Affected Huntington's disease patients present with a progressive dementia that can be detected with a variety of neuropsychological procedures. Neuropsychological findings include impaired mental flexibility and concentration, deterioration of verbal and procedural memory, diminished nonverbal memory, and slowing of both fine and gross motor functions. Magnetic resonance imaging (MRI) offers unique advantages in depicting morphologic changes associated with Huntington's disease. Frontotemporal atrophy and, in particular, atrophy of the corpus striatum are characteristically observed. Given the ease of obtaining coronal images and the improved differentiation of gray matter and white matter, MRI can provide better identification of these findings than traditional imaging methods such as computed tomography (CT). Finally, the presence of steadily progressive neuropsychological deterioration in conjunction with characteristic atrophy observed on MRI can be combined with diminished metabolic activity of the corpus striatum as observed on positron emission tomography (PET) for added diagnostic specificity.",,"Brooker, A. E.;Dougherty, D. S.;Love, K. F.;Kelly, W. M.",1991,Jun,,0,
5197,White matter lesions and soluble interleukin-1 receptor type II in CSF from demented and non-demented subjects,"White matter lesions (WMLs) in the brain is a common, unspecific finding on magnetic resonance imaging appearing both in the healthy elderly as well as in a number of different diseases including dementia disorders. However, the pathophysiological and clinical significance of WMLs in dementia disorders is still unknown. In this study, we investigated the possibility of their origin being inflammatory by studying the correlation between WMLs and cerebrospinal fluid (CSF) levels of the proinflammatory cytokine soluble interleukin-1 receptor type II (sIL-1RII). The sIL-1RII is a member of the",,"Bronge, L.;Wahlund, L. O.;Brauner, A.;Basun, H.;Garlind, A.",2002,2002,,0,
5198,Prognostic significance of white matter changes in a memory clinic population,"Non-specific white matter changes (WMC) can be seen on neuroimaging of the brain in healthy elderly but are more common in dementia. WMC are correlated to specific cognitive deficits and might also contribute to global cognitive decline. The value of WMC as a predictor of cognitive impairment has been incompletely elucidated. We studied the prognostic significance of extensive WMC in a group of patients with memory disturbances, to evaluate if the presence of such changes predicts a poorer outcome. We retrospectively selected a group of 24 patients with prominent WMC on magnetic resonance imaging (MRI) and with different grades of memory impairment. We matched each patient, with regard to age, education, length of follow-up, initial score on the Mini Mental State Examination (MMSE) and initial diagnosis, to a patient without white matter pathology. The matched pairs were evaluated and the decrease in MMSE score after follow-up (range 2-4 years) was used as the outcome measure. Results showed no difference in the decrease in MMSE score at follow-up between patients with or without WMC. In conclusion, the presence of WMC in cognitively impaired patients had no effect on the progression rate of dementia, as measured by MMSE decline.",Aged;Brain/ pathology;Dementia/diagnosis/ pathology;Diagnostic and Statistical Manual of Mental Disorders;Female;Follow-Up Studies;Humans;International Classification of Diseases;Magnetic Resonance Imaging;Male;Memory Disorders/ diagnosis/epidemiology;Middle Aged;Neuropsychological Tests;Predictive Value of Tests;Prognosis;Severity of Illness Index,"Bronge, L.;Wahlund, L. O.",2003,Apr 1,,0,
5199,White matter lesions in dementia: an MRI study on blood-brain barrier dysfunction,"White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common in dementia. Both conditions may be a consequence of small-vessel disease, in which case the BBB damage would be suspected to be located to the WMLs. To further evaluate the nature of WMLs in dementia we examined 10 demented patients with WMLs, including 5 cases with elevated CSF/serum albumin ratios as an indication of BBB damage. An optimised gadolinium (Gd)-enhanced MRI technique was used including a double dose of Gd, a 30-min scan time after injection and analysis of the MR signal in the WMLs as a function over time. Results showed no significant changes in MR signal in the WMLs after contrast administration. We conclude that WMLs are not connected to BBB damage to such a degree that is detectable with this method and that the elevated CSF albumin might have another origin.",Aged;Blood-Brain Barrier/*physiology;Brain/*pathology;Contrast Media;Dementia/*metabolism/*pathology;Female;Gadolinium DTPA;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Serum Albumin/cerebrospinal fluid/metabolism,"Bronge, L.;Wahlund, L. O.",2000,Sep-Oct,17248,0,
5200,White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype,"To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer's disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype sigma4/4 had more extensive WMLs in the deep white matter than patients with genotypes sigma3/3 and sigma3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE sigma3/3 genotype. In patients carrying at least one sigma4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele sigma4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.","Aged;Aged, 80 and over;Aging/pathology;Alzheimer Disease/ genetics/ pathology;Apolipoprotein E3;Apolipoprotein E4;Apolipoproteins E/ genetics;Basal Ganglia/pathology;Brain/ pathology;Cerebral Ventricles/pathology;Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Sex Factors","Bronge, L.;Fernaeus, S. E.;Blomberg, M.;Ingelson, M.;Lannfelt, L.;Isberg, B.;Wahlund, L. O.",1999,Mar-Apr,17107,0,
5201,"Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study","To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer's disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r(2) = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Postmortem Changes","Bronge, L.;Bogdanovic, N.;Wahlund, L. O.",2002,,57698,0,
5202,"MRI of the temporal lobe: normal variations, with special reference toward epilepsy","Recent investigations of epilepsy, Alzheimer's disease, amnesia, and schizophrenia have used magnetic resonance imaging (MRI) to evaluate changes in temporal lobe structures. Normal variations in these structures need to be defined before one can use these structures to describe abnormal conditions. Twenty-nine normal volunteers were studied by coronal MRI. Frequent findings include notching of the uncus by the tentorium or adjacent vessels (22/29) and asymmetry of the temporal horns (20/29). This finding of uncal notching strengthens the evidence against ""incisural sclerosis"" as the basis for hippocampal sclerosis. Temporal horn dilatation occurred in four. However, mild asymmetry of the temporal horn was seen frequently at its anterior tip (16/29) and may be related to head rotation. Asymmetry of the choroidal fissure was never marked. Mild asymmetry was common at the hippocampal head (pes). Mild enlargement of the right temporal lobe by visual inspection is not uncommon. Subtle asymmetry of the white matter between the hippocampus and the collateral sulcus occurred in six. The collateral sulcus does not always point to the temporal horn. The occipitotemporal sulcus may point to the temporal horn. Asymmetric uncal protrusion (0/29) and Sylvian fissure dilatation (4/29) occur rarely.","Cerebral Ventricles/anatomy & histology/pathology;Choroid Plexus/anatomy & histology/pathology;Dilatation, Pathologic/pathology;Epilepsy/ pathology;Hippocampus/anatomy & histology/pathology;Humans;Limbic System/anatomy & histology/pathology;Magnetic Resonance Imaging/methods;Temporal Lobe/ anatomy & histology/pathology","Bronen, R. A.;Cheung, G.",1991,,,0,
5203,Brain structure and function related to depression in Alzheimer's disease: Contributions from neuroimaging research,"The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in",,"Brommelhoff, J. A.;Sultzer, D. L.",2015,2015,,0,
5204,"Striatal Hypodensities, Not White Matter Hypodensities on CT, Are Associated with Late-Onset Depression in Alzheimer's Disease","This study examined whether there were neuroanatomical differences evident on CT scans of individuals with dementia who differed on depression history. Neuroanatomical variables consisted of visual ratings of frontal lobe deep white matter, subcortical white matter, and subcortical gray matter hypodensities in the CT scans of 182 individuals from the Study of Dementia in Swedish Twins who were diagnosed with dementia and had information on depression history. Compared to individuals with Alzheimer's disease and no depression, individuals with Alzheimer's disease and late-onset depression (first depressive episode at age 60 or over) had a greater number of striatal hypodensities (gray matter hypodensities in the caudate nucleus and lentiform nucleus). There were no significant differences in frontal lobe deep white matter or subcortical white matter. These findings suggest that late-onset depression may be a process that is distinct from the neurodegenerative changes caused by Alzheimer's disease.",,"Brommelhoff, J. A.;Spann, B. M.;Go, J. L.;Mack, W. J.;Gatz, M.",2011,,10.4061/2011/187219,0,
5205,White matter lesions and cerebral atrophy on MR images in patients with and without AIDS dementia complex,"OBJECTIVE: The objective of this study was threefold: to determine if the frequency of deep white matter changes and cerebral atrophy seen on MR images is significantly different between patients with and without AIDS dementia complex, to determine if certain patterns of white matter changes are more closely associated with AIDS dementia complex, and to determine if focal lesions within the white matter of the splenium are more common in AIDS dementia complex. MATERIALS AND METHODS: Forty-five patients with AIDS were clinically examined for AIDS dementia complex. MR images from these patients were retrospectively reviewed without knowledge of the clinical results. The presence or absence of white matter abnormalities and cerebral atrophy was evaluated by using graded scales and correlated with the presence or absence of AIDS dementia complex. RESULTS: Ten patients met the criteria for AIDS dementia complex. Eight of 25 patients in whom MR images showed abnormal signal intensity in deep white matter had dementia compared with two of 20 in whom MR showed no changes in deep white matter. The presence of these deep white matter abnormalities was not significantly different between groups with and without dementia (p = .08), although higher grades of deep white matter abnormality were more likely to be associated with AIDS dementia complex. Nine of 19 patients in whom MR images showed atrophy had dementia compared with one of 26 in whom MR showed no atrophy. Atrophy was significantly associated with AIDS dementia complex (p = .001). Eight of 15 patients in whom MR images showed abnormal signal intensity within the white matter of the splenium had dementia compared with two of 30 in whom MR showed normal signal intensity in this area. The degree of abnormality in the splenium was weakly associated with AIDS dementia complex (Kendall's tau = .471, p = .001). CONCLUSION: MR findings of cerebral atrophy and abnormal signal intensity in the splenium are associated with AIDS dementia complex. The presence of generalized deep white matter abnormalities does not differ significantly between patients with and without dementia, although more severe grades of white matter abnormality are more likely to be seen in patients with AIDS dementia complex.",AIDS Dementia Complex/ diagnosis/pathology;Acquired Immunodeficiency Syndrome/complications/ pathology;Adult;Atrophy/diagnosis;Brain/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Retrospective Studies,"Broderick, D. F.;Wippold, F. J., 2nd;Clifford, D. B.;Kido, D.;Wilson, B. S.",1993,Jul,10.2214/ajr.161.1.8517298,0,
5206,Preclinical characterization of a novel class of 18F-labeled PET tracers for amyloid-beta,"Imaging of amyloid-beta (Abeta) plaques by PET is more and more integrated into concepts for Alzheimer disease (AD) diagnosis and drug development. The objective of this study was to find novel chemical entities that can be transformed into (18)F-labeled Abeta tracers with favorable brain washout kinetics and low background signal. METHODS: High-throughput screening of a large chemical library was used to identify new ligands for fibrillar aggregates of Abeta(1-42) peptide. Thirty-two fluorinated derivatives were synthesized and tested for their affinity toward AD brain homogenate. Twelve ligands have been radiolabeled with (18)F. The pharmacokinetic properties of the radioligands were investigated in mouse and monkey biodistribution studies. Binding characteristics were determined by autoradiography of AD brain sections in vitro and using amyloid precursor protein transgenic mice in vivo. RESULTS: The systematic search for Abeta imaging agents revealed several fluorinated derivatives with nanomolar affinity for Abeta. The fluoropyridyl derivative BAY 1008472 showed a high initial brain uptake (6.45 percentage injected dose per gram at 2 min) and rapid brain washout (ratio of percentage of injected dose per gram of tissue at 2 and 30 min after injection, 9.2) in mice. PET studies of healthy rhesus monkeys confirmed the high initial brain uptake of BAY 1008472 (2.52 standardized uptake value at peak) and a fast elimination of total radioactivity from gray and white matter areas (ratio of standardized uptake value at peak uptake and 60 min 11.0). In autoradiographic analysis, BAY 1008472 selectively detected Abeta deposits in human AD brain sections with high contrast and did not bind to tau- or alpha-synuclein pathologies. Finally, ex vivo autoradiography of brain sections from amyloid precursor protein-transgenic mice confirmed that BAY 1008472 is indeed suitable for the in vivo detection of Abeta plaques. CONCLUSION: A new chemical class of Abeta tracers has been identified by high-throughput screening. The fluoropyridyl derivative BAY 1008472 shows a favorable preclinical profile including low background binding in gray and white matter. These properties might qualify this new tracer, in particular, to detect subtle amounts or changes of Abeta burden in presymptomatic AD and during therapy.",Amyloid beta-Peptides/ metabolism;Animals;Female;Fluorine Radioisotopes;Frontal Lobe/metabolism/radionuclide imaging;Half-Life;Humans;Macaca mulatta;Male;Mice;Positron-Emission Tomography/ methods;Pyridines/chemistry/metabolism/pharmacokinetics;Radioactive Tracers,"Brockschnieder, D.;Schmitt-Willich, H.;Heinrich, T.;Varrone, A.;Gulyas, B.;Toth, M.;Andersson, J.;Boemer, U.;Krause, S.;Friebe, M.;Dinkelborg, L.;Halldin, C.;Dyrks, T.",2012,Nov,10.2967/jnumed.112.104810,0,
5207,KIAA1797/FOCAD encodes a novel focal adhesion protein with tumour suppressor function in gliomas,"In a strategy to identify novel genes involved in glioma pathogenesis by molecular characterization of chromosomal translocation breakpoints, we identified the KIAA1797 gene, encoding a protein with an as yet undefined function, to be disrupted by a 7;9 translocation in a primary glioblastoma culture. Array-based comparative genomic hybridization detected deletions involving KIAA1797 in around half of glioblastoma cell lines and glioblastomas investigated. Quantification of messenger RNA levels in human tissues demonstrated highest KIAA1797 expression in brain, reduced levels in all glioblastoma cell lines and most glioblastomas and similar levels in glial and neuronal cells by analysis of different hippocampal regions from murine brain. Antibodies against KIAA1797 were generated and showed similar protein levels in cortex and subcortical white matter of human brain, while levels were significantly reduced in glioblastomas with KIAA1797 deletion. By immunofluorescence of astrocytoma cells, KIAA1797 co-localized with vinculin in focal adhesions. Physical interaction between KIAA1797 and vinculin was demonstrated via co-immunoprecipitation. Functional in vitro assays demonstrated a significant decrease in colony formation, migration and invasion capacity of LN18 and U87MG glioma cells carrying a homozygous KIAA1797 deletion ectopically expressing KIAA1797 compared with mock-transduced cells. In an in vivo orthotopic xenograft mouse model, U87MG tumour lesions expressing KIAA1797 had a significantly reduced volume compared to tumours not expressing KIAA1797. In summary, the frequently deleted KIAA1797 gene encodes a novel focal adhesion complex protein with tumour suppressor function in gliomas, which we name 'focadhesin'. Since KIAA1797 genetic variation has been implicated in Alzheimer's disease, our data are also relevant for neurodegeneration.","Animals;Animals, Newborn;Brain/metabolism;Brain Neoplasms/*genetics;Cell Line, Tumor;Cell Movement/genetics;Comparative Genomic Hybridization;Cyclin-Dependent Kinase Inhibitor p15/metabolism;Cyclin-Dependent Kinase Inhibitor p16/metabolism;Disease Models, Animal;Female;Focal Adhesions/*genetics/immunology/metabolism;Gadolinium;Gene Expression Regulation, Neoplastic/genetics/*physiology;Genes, Tumor Suppressor/*physiology;Glioblastoma/*genetics;Green Fluorescent Proteins/genetics/metabolism;Humans;Immunoprecipitation;In Vitro Techniques;Magnetic Resonance Imaging;Male;Mice;Mice, Inbred C57BL;Mice, Nude;Neuroglia/metabolism;Neurons/metabolism;RNA, Messenger/metabolism;Transfection;Tumor Stem Cell Assay/methods;Tumor Suppressor Proteins/genetics/metabolism;Vinculin/metabolism;Xenograft Model Antitumor Assays","Brockschmidt, A.;Trost, D.;Peterziel, H.;Zimmermann, K.;Ehrler, M.;Grassmann, H.;Pfenning, P. N.;Waha, A.;Wohlleber, D.;Brockschmidt, F. F.;Jugold, M.;Hoischen, A.;Kalla, C.;Waha, A.;Seifert, G.;Knolle, P. A.;Latz, E.;Hans, V. H.;Wick, W.;Pfeifer, A.;Angel, P.;Weber, R. G.",2012,Apr,10.1093/brain/aws045,0,
5208,Complicated hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) and childhood onset,"The hereditary spastic paraplegias (HSPs) are a group of rare disorders with the predominant clinical feature of progressive spastic paraplegia. They are subdivided into pure and complicated forms according to whether the disorder is associated with other neurological abnormalities. We report on two unrelated female Caucasian patients with complicated HSP, aged 16 and 24 years, who showed progressive gait disturbance with spasticity and ataxia as well as cognitive impairment. Onset of symptoms was at age 3 and 10 years, respectively. MRI revealed mild diffuse non-progressive T2-signal alterations of cerebral white matter and thinning of the body and genu of the corpus callosum. Some similarity of clinical symptoms and MRI patterns with the phenotype of Mast syndrome prompted a mutation analysis of the SPG21 gene, encoding maspardin, which revealed a wild-type sequence in both patients. Clinical and neuroradiological features in our patients are diagnostic for complicated autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC, SPG11). This disorder, characterized by a typical MRI pattern and a progressive spastic paraplegia that may be associated with dementia and ataxia, may have an onset in early childhood and probably is one of the more common forms of complicated HSP. © Georg Thieme Verlag KG Stuttgart.",maspardin;protein;unclassified drug;adolescent;article;ataxia;autosomal recessive disorder;case report;Caucasian;child;clinical feature;cognitive defect;corpus callosum;dementia;disease association;female;gait disorder;gene;gene mutation;genetic disorder;hereditary motor sensory neuropathy;human;neuroradiology;nuclear magnetic resonance imaging;priority journal;spasticity;SPG21 gene,"Brockmann, K.;Simpson, M. A.;Faber, A.;Bönnemann, C.;Crosby, A. H.;Gärtner, J.",2005,,,0,
5209,Classic Pick's disease type with ubiquitin-positive and tau-negative inclusions: case report,"We report on a patient presenting Pick's disease similar to the one reported by Pick in 1892, with ubiquitin-positive and tau-negative inclusions. His diagnosis was made on the basis of clinical (language disturbance and behavioural disorders), neuropsychological (progressive aphasia of the expression type and late mutism), neuroimaging with magnetic resonance (bilateral frontal and temporal lobes atrophy) and brain single photon emission computed tomography (frontal and temporal lobes hypoperfusion) studies. Macroscopic examination showed atrophy on the frontal and temporal lobes. The left hippocampus displayed a major circumscribed atrophy. The diagnostic confirmation was made by the neuropathological findings of the autopsy that showed neuronal loss with gliosis of the adjacent white matter and apearance of status spongiosus in the middle frontal and especially in the upper temporal lobes. There were also neuronal swelling (ballooned cell) and argyrophilic inclusions (Pick's bodies) in the left and right hippocampi. Anti-ubiquitin reaction tested positive and anti-tau tested negative.",tau protein;ubiquitin;aged;article;atrophy;case report;computer assisted tomography;fatality;frontal lobe;hippocampus;human;male;neuropsychological test;pathology;Pick presenile dementia;single photon emission computer tomography;temporal lobe,"Brito-Marques, P. R.;Mello, R. V.;Montenegro, L.",2001,,,0,
5210,Aerobic exercise increases cortical white matter volume in older adults with vascular cognitive impairment: A 6-month randomized controlled trial,"Background: Worldwide, Sub-cortical vascular ischaemia (SVCI) is the second most common etiology contributing to cognitive impairment among older adults. Yet, SVCI may be the most treatable form of cognitive impairment as many of its risk factors can be reduced with exercise. Nevertheless, few randomized controlled trials to date have specifically assessed the efficacy of exercise training on cognitive and brain outcomes in this high-risk group. Thus, we conducted a 6-month proof-of-concept randomized controlled trial of thrice-weekly aerobic exercise training (AE) among adults with mild SVCI. A sub-set of participants underwent MRI scanning; the focus of this analysis was to investigate the effect of AE on both white matter and grey matter in this sub-set. Methods: Seventy- one adults (56-96 years) with SVCI were recruited and randomized (1:1) to one of two experimental groups: 1) 3x/week AE or 2) usual care (UC). SVCI was confirmed by: 1) evidence of subcortical white matter lesions from neuroimaging (i.e., CT or MRI); 2) a score of less than 26 on the Montreal Cognitive Assessment (MoCA); and 3) clinical assessment by neurologist. Thirty participants (16 from AE and 14 from UC) completed 3T MRI scanning both at baseline and trial completion. Scans were analyzed using FSL Freesurfer. Results: Compared with the control group, cortical white matter volume significantly increased in the AE group (p = .039). However, total grey matter volume significantly decreased in the AE group compared with the UC group (p= .043). Conclusions: A 6-month AE program significantly increased white matter volume in older adults diagnosed with VCI compared with the control group. However, future studies are need to confirm our current results.",white matter;adult;cognitive defect;human;randomized controlled trial;aerobic exercise;exercise;gray matter;control group;nuclear magnetic resonance imaging;ischemia;Montreal cognitive assessment;randomized controlled trial(topic);neuroimaging;white matter lesion;high risk population;clinical assessment;neurologist;brain;risk factor;imaging software;etiology,"Brinke, L. F.;Liang, Hsu C.;Chiu, B. K.;Bolandzadeh, N.;Dao, E.;Hsiung, G. Yr;Eng, J. J.;Boyd, L.;Munkacsy, M.;Lee, P. E.;Jacova, C.;Liu-Ambrose, T.",2015,,,0,
5211,Dementia and white-matter demyelination in young patient with neurosyphilis,,penicillin G;procaine penicillin;adult;article;case report;cerebrospinal fluid analysis;clinical feature;dementia;demyelination;human;male;memory disorder;Mini Mental State Examination;neurologic examination;neurosyphilis;nuclear magnetic resonance imaging;priority journal;speech disorder;Treponema pallidum hemagglutination test;venereal disease reaction test;white matter,"Brinar, V. V.;Habek, M.",2006,,,0,
5212,Rarefied white matter in patients with Alzheimer disease,"Magnetic resonance head scans of 94 patients with probable Alzheimer disease (AD) and 45 patients with possible AD were examined prospectively to determine the prevalence and significance of rarefied cerebral white matter (leukoaraiosis) in patients with AD. Only 8.7% of patients with probable AD and 11.1% of patients with possible AD exhibited large confluent areas of subcortical leukoaraiosis. The remaining patients had variable degrees of leukoaraiosis surrounding the lateral ventricles. The magnitude of leukoaraiosis correlated with the patient's age but not with the Hachinski Ischemic and Mini Mental Status scores. Postmortem studies of two Alzheimer patients showed that their large confluent areas of subcortical leukoaraiosis consisted of rarefied white matter, gliosis, and arteriosclerotic small arteries. Eight additional Alzheimer patients who underwent autopsy had similar but less pronounced white matter changes limited to the periventricular regions of the cerebral hemispheres. Large confluent areas of rarefied subcortical white matter occur in a small minority of Alzheimer patients and are probably not caused by AD.",Aged;Alzheimer Disease/*diagnosis/pathology;Atrophy;Brain/*pathology;Cerebral Amyloid Angiopathy/diagnosis/pathology;Cerebral Cortex/pathology;Cerebral Ventricles/pathology;Female;Humans;*Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prospective Studies,"Brilliant, M.;Hughes, L.;Anderson, D.;Ghobrial, M.;Elble, R.",1995,Spring,,0,
5213,Neurosyphilis in HIV-positive and HIV-negative patients: neuroimaging findings,"PURPOSE: To evaluate and describe the neuroimaging findings of patients with neurosyphilis. METHODS: The neuroimaging studies of 35 patients with documented neurosyphilis were reviewed. Diagnosis was established in 34 patients with cerebrospinal fluid for a Venereal Disease Research Laboratory test, complemented by autopsy in 1 and brain biopsy in 1. All patients had reactive fluorescent treponemal antibody tests with absorption in their sera. Imaging studies included plain and contrast-enhanced CT of the brain, plain and gadolinium-enhanced MR, MR angiography, and conventional angiography. Imaging findings were also correlated with the relevant pathologic findings at autopsy in three additional patients with neurosyphilis who did not have brain imaging studies. RESULTS: Of the 35 patients with imaging studies, 32 tested human immunodeficiency virus (HIV)-seropositive, and 3 were HIV-seronegative. Eleven (31%) of 35 patients had normal radiographic findings. Cerebral infarctions were seen in 8 (23%) of 35 patients, and nonspecific white matter lesions in 7 (20%) of 35. Cerebral gummas and extraaxial enhancement indicating meningitis were noted in 2 (6%) of 35 patients, respectively. Arteritis was demonstrated in 2 (50%) of 4 patients who underwent either MR angiography or conventional angiography. The 3 subjects who had autopsy but not imaging studies were found to have manifestations of meningovascular syphilis, including syphilitic leptomeningitis and an obliterative endarteritis. CONCLUSION: We conclude that findings of vascular occlusive disease manifested as infarction or arteritis, enhancing cortical lesions with or without adjacent meningeal enhancement, focal or diffuse extraaxial enhancement, and white matter disease, although nonspecific, in the proper clinical setting should prompt appropriate testing for neurosyphilis, a treatable disease, in patients with and without HIV infection.","AIDS Dementia Complex/ diagnosis/pathology;AIDS-Related Opportunistic Infections/ diagnosis/pathology;Adult;Brain/pathology;Cerebral Angiography;Cerebral Infarction/diagnosis/pathology;Diagnostic Imaging;Female;HIV Seronegativity;HIV Seropositivity/ diagnosis/pathology;Humans;Intracranial Embolism and Thrombosis/diagnosis/pathology;Magnetic Resonance Imaging;Male;Meningitis/diagnosis/pathology;Middle Aged;Neurosyphilis/ diagnosis/pathology;Tomography, X-Ray Computed","Brightbill, T. C.;Ihmeidan, I. H.;Post, M. J.;Berger, J. R.;Katz, D. A.",1995,Apr,,0,
5214,Regional White Matter and Neuropsychological Functioning across the Adult Lifespan,"Background: The current study utilized magnetic resonance imaging (MRI) to more fully elucidate the relationship among age, regional white matter, and neuropsychological functioning. Methods: One hundred ninety-nine neurologically healthy adults received MRI and standardized neuropsychological assessment. MR images were spatially normalized and segmented by tissue type; relative white matter values in each of the four cerebral lobes in each hemisphere were computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54), and Older (ages 55-79) age groups. Results: The Older group had significantly less overall relative white matter than the Middle group, who had significantly less overall relative white matter than the Younger participants (F (2, 193) = 5.42, p = 0.005). Differences in frontal lobe white matter were of largest magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and frontal and temporal lobe white matter were primarily associated with performance on neuropsychological tests of executive functioning and memory. Mediational analysis suggested that frontal lobe white matter mediated the relationship between age and performance on tasks of executive functioning and memory. Conclusions: The results confirm age-associated decline in frontal and temporal white matter, and age-related cognitive decline in several domains. Decline in neuropsychological functioning is, in part, mediated by a relative age-related reduction in frontal white matter. © 2006 Society of Biological Psychiatry.",,"Brickman, A. M.;Zimmerman, M. E.;Paul, R. H.;Grieve, S. M.;Tate, D. F.;Cohen, R. A.;Williams, L. M.;Clark, C. R.;Gordon, E.",2006,1,,0,
5215,Reconsidering harbingers of dementia: Progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence,"Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD.",aged;Alzheimer disease;article;brain atrophy;brain size;cohort analysis;controlled study;cortical thickness (brain);dementia;disease activity;disease association;disease course;disease marker;female;hippocampus;human;incidence;major clinical study;male;nerve degeneration;parietal lobe;prediction;radiological parameters;white matter;white matter hyperintensity,"Brickman, A. M.;Zahodne, L. B.;Guzman, V. A.;Narkhede, A.;Meier, I. B.;Griffith, E. Y.;Provenzano, F. A.;Schupf, N.;Manly, J. J.;Stern, Y.;Luchsinger, J. A.;Mayeux, R.",2015,,10.1016/j.neurobiolaging.2014.07.019,0,5216
5216,Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence,"Accumulating evidence implicates small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging, in the pathogenesis and diagnosis of Alzheimer's disease (AD). Cross-sectional volumetric measures of WMH, particularly in the parietal lobes, are associated with increased risk of AD. In the present study, we sought to determine whether the longitudinal regional progression of WMH predicts incident AD above-and-beyond traditional radiological markers of neurodegeneration (i.e., hippocampal atrophy and cortical thickness). Three hundred three nondemented older adults (mean age = 79.24 ± 5.29) received high-resolution magnetic resonance imaging at baseline and then again 4.6 years (standard deviation = 1.01) later. Over the follow-up interval 26 participants progressed to AD. Using structural equation modeling, we calculated latent difference scores of parietal and nonparietal WMH, hippocampus volumes, and cortical thickness values in AD-related regions. Within the structural equation modeling framework, we determined whether baseline or change scores or both predicted AD conversion, while controlling for several time-invariant relevant variables. Smaller baseline hippocampus volume, change in hippocampus volume (i.e., atrophy), higher baseline parietal lobe WMH, and increasing parietal lobe WMH volume but not WMH in other regions or measures of cortical thickness, independently predicted progression to AD. The findings provide strong evidence that regionally accumulating WMH predict AD onset in addition to hallmark neurodegenerative changes typically associated with AD. © 2014 Elsevier Inc. All rights reserved.",,"Brickman, A. M.;Zahodne, L. B.;Guzman, V. A.;Narkhede, A.;Meier, I. B.;Griffith, E. Y.;Provenzano, F. A.;Schupf, N.;Manly, J. J.;Stern, Y.;Luchsinger, J. A.;Mayeux, R.",2014,,,0,
5217,White matter hyperintensities and cognition: Testing the reserve hypothesis,"Objective: White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve. Methods: Neurologically healthy older adults (n= 717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively. Results: Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume. Conclusions: For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition. © 2009 Elsevier Inc.",aged;aging;analytical parameters;anthropometric parameters;article;cognition;cognitive reserve;community assessment;controlled study;craniometry;educational status;executive function;female;human;human experiment;language ability;male;neuropsychological test;normal human;nuclear magnetic resonance imaging;priority journal;prospective study;radiological parameters;sex difference;social psychology;structural equation modeling;T2 weighted imaging;white matter hyperintensities;white matter hyperintensities volume,"Brickman, A. M.;Siedlecki, K. L.;Muraskin, J.;Manly, J. J.;Luchsinger, J. A.;Yeung, L. K.;Brown, T. R.;DeCarli, C.;Stern, Y.",2011,,,0,
5218,APOE ε4 and risk for Alzheimer's disease: Do regionally distributed white matter hyperintensities play a role?,"Background We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume. Methods Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis. Results In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH. Conclusions APOE ε4 is associated with increased parietal lobe WMH.",apolipoprotein E4;aged;Alzheimer disease;article;brain size;comorbidity;female;genotype;human;major clinical study;male;neuroimaging;neurologic examination;neuropathology;nuclear magnetic resonance imaging;occipital lobe;parietal lobe;priority journal;risk assessment;risk factor;temporal lobe;white matter hyperintensity,"Brickman, A. M.;Schupf, N.;Manly, J. J.;Stern, Y.;Luchsinger, J. A.;Provenzano, F. A.;Narkhede, A.;Razlighi, Q.;Collins-Praino, L.;Artero, S.;Akbaraly, T. N.;Ritchie, K.;Mayeux, R.;Portet, F.",2014,,,0,
5219,APOE epsilon4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?,"BACKGROUND: We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE epsilon4) have increased parietal WMH volume. METHODS: Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Sante Psychologique Prevalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE epsilon4 was examined separately in each group and then in a combined analysis. RESULTS: In WHICAP, epsilon4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, epsilon4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, epsilon4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE epsilon4 status; those with the epsilon4 were more likely to have dementia if they also had increased parietal WMH. CONCLUSIONS: APOE epsilon4 is associated with increased parietal lobe WMH.","Aged;Aged, 80 and over;Alzheimer Disease/*genetics/*pathology;Analysis of Variance;Apolipoprotein E4/*genetics;Female;Genotype;Humans;Image Processing, Computer-Assisted;Linear Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Neurologic Examination;Neuropsychological Tests;Parietal Lobe/*pathology;Retrospective Studies;White Matter/*pathology;Apoe;Alzheimer's disease;White matter hyperintensities","Brickman, A. M.;Schupf, N.;Manly, J. J.;Stern, Y.;Luchsinger, J. A.;Provenzano, F. A.;Narkhede, A.;Razlighi, Q.;Collins-Praino, L.;Artero, S.;Akbaraly, T. N.;Ritchie, K.;Mayeux, R.;Portet, F.",2014,Nov,10.1016/j.jalz.2014.07.155,0,
5220,"Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan","BACKGROUND: Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. OBJECTIVE: To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. DESIGN: The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered. SETTING: The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. PARTICIPANTS: Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. MAIN OUTCOME MEASURES: Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images. RESULTS: Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. CONCLUSIONS: Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.","African Americans/ ethnology;Aged;Aged, 80 and over;Aging/pathology/ physiology;Anatomy, Cross-Sectional;Atrophy;Brain/ anatomy & histology/pathology;Caribbean Region/ethnology;Cohort Studies;Dementia/diagnosis/epidemiology/pathology/physiopathology;European Continental Ancestry Group/ ethnology;Female;Follow-Up Studies;Hispanic Americans/ ethnology;Humans;Magnetic Resonance Imaging;Male;New York City/epidemiology/ethnology;Prospective Studies;Risk Factors;Vascular Diseases/epidemiology/pathology/physiopathology","Brickman, A. M.;Schupf, N.;Manly, J. J.;Luchsinger, J. A.;Andrews, H.;Tang, M. X.;Reitz, C.;Small, S. A.;Mayeux, R.;DeCarli, C.;Brown, T. R.",2008,Aug,10.1001/archneur.65.8.1053,0,
5221,Long-term blood pressure fluctuation and cerebrovascular disease in an elderly cohort,"Background: The importance of subclinical cerebrovascular disease in the elderly is increasingly recognized, but its determinants have not been fully explicated. Elevated blood pressure (BP) and fluctuation in BP may lead to cerebrovascular disease through ischemic changes and compromised cerebral autoregulation. Objective: To determine the association of BP and longterm fluctuation in BP with cerebrovascular disease. Design: A community-based epidemiological study of older adults from northern Manhattan. Setting: The Washington Heights - Inwood Columbia Aging Project. Participants: A total of 686 nondemented older adults who had BP measurements during 3 study visits at 24-month intervals and underwent structural magnetic resonance imaging (corresponding temporally with the third assessment). We derived the mean (SD) of the mean BP for each participant during the 3 intervals and divided the participants into 4 groups defined as below or above the group median (≤96.48 or >96.48 mm Hg) and further subdivided them as below or above the median SD (≤7.21 or >7.21mmHg). This scheme yielded 4 groups representing the full range of BPs and fluctuations in BP. Main Outcome Measures: Differences in white matter hyperintensity (WMH) volume and presence of brain infarctions across groups. Results: White matter hyperintensity volume increased across the 4 groups in a linear manner, with the lowestWMHvolume in the lowest mean/lowest SD group and the highest WMH volume in the highest mean/highest SD group (F (3,610)=3.52, P=.02). Frequency of infarction also increased monotonically across groups (from 22% to 41%, P for trend=.004). Conclusions: Compared with individuals with low BP and low fluctuations in BP, the risk of cerebrovascular disease increased with higher BP and BP fluctuations. Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating BP and elevated BP. ©2010 American Medical Association. All rights reserved.",,"Brickman, A. M.;Reitz, C.;Luchsinger, J. A.;Manly, J. J.;Schupf, N.;Muraskin, J.;DeCarli, C.;Brown, T. R.;Mayeux, R.",2010,May,,0,
5222,Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?,"The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.","Aging/pathology;Alzheimer Disease/ pathology/physiopathology;Brain/ pathology/physiopathology;Cognition Disorders/pathology/physiopathology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Nerve Fibers, Myelinated/ pathology/physiology","Brickman, A. M.;Muraskin, J.;Zimmerman, M. E.",2009,,,0,
5223,Testing the white matter retrogenesis hypothesis of cognitive aging,"The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (. n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status.",,"Brickman, A. M.;Meier, I. B.;Korgaonkar, M. S.;Provenzano, F. A.;Grieve, S. M.;Siedlecki, K. L.;Wasserman, B. T.;Williams, L. M.;Zimmerman, M. E.",2012,August,,0,
5224,Measuring cerebral atrophy and white matter hyperintensity burden to predict the rate of cognitive decline in Alzheimer disease,"OBJECTIVE: To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD). DESIGN: Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits. SETTING: Three university-based AD centers in the United States. PARTICIPANTS: At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure The mMMS score. RESULTS: Generalized estimating equation models demonstrated that the degree of baseline atrophy (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -6.061; P = .02) predicted the rate of decline in mMMS scores. CONCLUSIONS: Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/psychology;Atrophy;Brain/ pathology;Brief Psychiatric Rating Scale/standards;Cognition Disorders/ pathology/psychology;Cohort Studies;Female;Follow-Up Studies;Humans;Longitudinal Studies;Male;Nerve Fibers, Myelinated/ pathology;Neurodegenerative Diseases/pathology/psychology;Predictive Value of Tests;Research Design/ standards","Brickman, A. M.;Honig, L. S.;Scarmeas, N.;Tatarina, O.;Sanders, L.;Albert, M. S.;Brandt, J.;Blacker, D.;Stern, Y.",2008,Sep,10.1001/archneur.65.9.1202,0,
5225,"Cerebral autoregulation, beta amyloid, and white matter hyperintensities are interrelated","Emerging studies link vascular risk factors and cerebrovascular health to the prevalence and rates of progression in Alzheimer's disease (AD). The brain's ability to maintain constant blood flow across a range of cerebral perfusion pressures, or autoregulation, may both promote and result from small vessel cerebrovascular disease and AD-related amyloid pathology. Here, we examined the relationship among cerebral autoregulation, small vessel cerebrovascular disease, and amyloid deposition in 14 non-demented older adults. Reduced cerebral autoregulation, was associated with increased amyloid deposition and increased white matter hyperintensity volume, which, in turn were positively associated with each other. For the first time in humans, we demonstrate an interrelationship among AD pathology, small vessel cerebrovascular disease, and cerebral autoregulation. Vascular factors and AD pathology are not independent but rather appear to interact.",amyloid beta protein;aged;Alzheimer disease;article;autoregulation;brain size;cardiovascular risk;cerebral autoregulation;cerebrovascular disease;clinical article;disease association;disease marker;Doppler echography;female;human;male;neuroimaging;nuclear magnetic resonance imaging;positron emission tomography;priority journal;white matter;white matter hyperintensity,"Brickman, A. M.;Guzman, V. A.;Gonzalez-Castellon, M.;Razlighi, Q.;Gu, Y.;Narkhede, A.;Janicki, S.;Ichise, M.;Stern, Y.;Manly, J. J.;Schupf, N.;Marshall, R. S.",2015,,,0,
5226,Contemplating Alzheimer's disease and the contribution of white matter hyperintensities,"As the older adult segment of the population increases, Alzheimer's disease (AD) has emerged as a significant public health epidemic. Over the past 3 decades, advances in the understanding of the biology of AD have led to a somewhat unified hypothesis of disease pathogenesis that emphasizes the precipitating role of beta amyloid protein. However, several lines of evidence suggest that multiple pathologies are necessary for clinical manifestation of the disease. Our focus over the past several years has been on the contribution of small vessel cerebrovascular disease, visualized as white matter hyperintensities (WMH) on magnetic resonance imaging, to AD. White matter hyperintensity volume, particularly in parietal regions, is elevated among individuals with and at risk for AD, predicts future diagnosis of AD, predicts the rate of progression of cognitive symptoms among individuals with AD, and increases over time among individuals destined to develop AD. White matter hyperintensities may represent an independent source of impairment and/or may interact more fundamentally with ""primary"" AD pathology. Future work should focus on more inclusive models of that better define ""normal"" vs ""pathological"" aging. © 2013 Springer Science+Business Media New York.",,"Brickman, A. M.",2013,,,0,
5227,Peripheral artery disease as a manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and practical implications,,Notch3 receptor;osmium;adult;amnesia;arteriography;article;ataxia;bradycardia;CADASIL;case report;dementia;digital artery;electrocardiogram;electron microscopy;gene mutation;headache;human;hypertension;hypothermia;kidney disease;male;nuclear magnetic resonance imaging;peripheral occlusive artery disease;pharmacologic stress testing;priority journal;right coronary artery;sinus bradycardia;toe gangrene;tremor,"Briceno, D. F.;Bhattacharjee, M. B.;Supsupin Jr, E.;Navarro, P.;Bhattacharjee, M.",2013,,,0,
5228,"Response to letters regarding article, ""peripheral Artery Disease as a Manifestation of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and practical implications""",,aortography;arteriography;CADASIL;clinical evaluation;electron microscopy;human;letter;neuroimaging;nuclear magnetic resonance imaging;peripheral occlusive artery disease;priority journal;risk factor,"Briceno, D. F.;Bhattacharjee, M. B.;Supsupin, E.;Navarro, P.;Bhattacharjee, M.",2013,,,0,
5229,Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam Study,"BACKGROUND AND PURPOSE: Ventricular enlargement and white matter lesions are frequent findings on cerebral magnetic resonance imaging scans of elderly subjects. In demented subjects they seem related to the severity of the dementia, but in nondemented subjects their clinical significance is less clear. We investigated the relation of size of the lateral ventricles and white matter lesions with cognitive function in a population-based random sample of nondemented elderly persons. METHODS: The study population consisted of 90 subjects, aged 65 to 84 years, who were randomly selected from the cohort of the Rotterdam Study, and who were not demented. The presence of white matter lesions and the ventricle-to-brain ratio were assessed on magnetic resonance scans. Participants were tested with a neuropsychological battery that covered a broad range of cognitive functions. RESULTS: Ventricular enlargement and white matter lesions were both and independently associated with poorer performance on all tests. After adjustment for age and sex, ventricular enlargement was significantly associated with worse scores on tests assessing global cognitive function (Mini-Mental State Examination, P = .02; Groninger Intelligence Test, P = .01), memory (Word List Learning delayed recall, P = .03), and executive control functions (Stroop part II, P = .02; Trial Making Test B, P < .01); for white matter lesions the differences were significant for tests measuring executive control functions and mental speed (Trail Making Test A and B, P = .01 and P < .01, respectively; verbal fluency, P = .01), and memory (Word List Learning delayed recall, P = .04). CONCLUSIONS: This study suggests that white matter lesions are primarily related to impairment of subcorticofrontal functions, whereas enlargement of the lateral ventricles is associated with disturbances of cortical functions as well.","Age Factors;Aged;Aged, 80 and over;Brain/pathology;Brain Diseases/ pathology/psychology;Cerebral Ventricles/ pathology;Cognition/ physiology;Cohort Studies;Educational Status;Female;Follow-Up Studies;Humans;Hypertrophy;Intelligence/physiology;Magnetic Resonance Imaging/methods;Male;Memory/physiology;Netherlands;Neuropsychological Tests;Prospective Studies","Breteler, M. M.;van Amerongen, N. M.;van Swieten, J. C.;Claus, J. J.;Grobbee, D. E.;van Gijn, J.;Hofman, A.;van Harskamp, F.",1994,Jun,,0,
5230,Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study,"Amyloid imaging by small-animal PET in models of Alzheimer disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Because microglial activation is thought to contribute to AD pathology, we undertook a triple-tracer small-animal PET study to assess microglial activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model. METHODS: Groups of PS2APP and C57BL/6 wild-type mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with (18)F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30- to 60-min recordings with (18)F-FDG for energy metabolism and (18)F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer (18)F-GE180, we then calculated distribution volume ratios after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary beta-amyloid, and ex vivo autoradiography served as terminal gold standard assessments. RESULTS: SUVR at 60-90 min after injection gave robust quantitation of (18)F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region. Relative to age-matched wild-type, (18)F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (+9%; P < 0.01) and distinctly increased at 16 mo (+25%; P < 0.001). Over this age range, there was a high positive correlation between small-animal PET findings of microglial activation with amyloid load (R = 0.85; P < 0.001) and likewise with metabolism (R = 0.61; P < 0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo small-animal PET data. CONCLUSION: In this first triple-tracer small-animal PET in a well-established AD mouse model, we found evidence for age-dependent microglial activation. This activation, correlating positively with the amyloid load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model.",18f-ge180;Alzheimer's disease;Tspo;neuroinflammation;small animal PET,"Brendel, M.;Probst, F.;Jaworska, A.;Overhoff, F.;Korzhova, V.;Albert, N. L.;Beck, R.;Lindner, S.;Gildehaus, F. J.;Baumann, K.;Bartenstein, P.;Kleinberger, G.;Haass, C.;Herms, J.;Rominger, A.",2016,Jun,10.2967/jnumed.115.167858,0,
5231,Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple Tracer PET Study,"Amyloid imaging by small animal PET (microPET) in models of Alzheimer's disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Since microglial activation is thought to contribute to AD pathology, we undertook a triple tracer microPET study to assess microglia activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model. METHODS: Groups of PS2APP and C57Bl/6 wild-type (WT) mice of various ages were examined by microPET. We acquired 90 min dynamic emission data with 18F-GE180 for imaging activated microglia (18kD translocator protein ligand, TSPO), and static 30-60 min recordings with 18F-FDG for energy metabolism and 18F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic non-linear spatial normalization, and standardized-uptake-value-ratios (SUVR) were calculated. For the novel TSPO tracer 18F-GE180, we then calculated distribution volume ratios (DVR) after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary beta-amyloid, and ex vivo autoradiography served as terminal gold standard assessments. RESULTS: SUVR at 60-90 min p.i. gave robust quantitation of 18F-GE180, which correlated well with DVR calculated from the entire recording, and using a white matter reference region. Relative to age-matched WT, 18F-GE180 SUVR was slightly elevated in PS2APP mice at five months (+9%; p<0.01), and distinctly increased at 16 months (+25%; p<0.001). Over this age range, there was high positive correlation between microPET findings of microglial activation with amyloid load (R=0.85; p<0.001), and likewise with metabolism (R=0.61; p<0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo microPET data. CONCLUSION: In this first triple tracer microPET in a well-established AD mouse model, we find evidence for age-dependent microglia activation. This activation, correlating positively with the amyloid-load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model.",,"Brendel, M.;Probst, F.;Jaworska, A.;Overhoff, F.;Korzhova, V.;Albert, N.;Beck, R.;Lindner, S.;Gildehaus, F. J.;Baumann, K.;Bartenstein, P.;Kleinberger, G.;Haass, C.;Herms, J.;Rominger, A.",2016,Feb 18,10.2967/jnumed.115.167858,0,
5232,Improved longitudinal [(18)F]-AV45 amyloid PET by white matter reference and VOI-based partial volume effect correction,"Amyloid positron-emission-tomography (PET) offers an important research and diagnostic tool for investigating Alzheimer's disease (AD). The majority of amyloid PET studies have used the cerebellum as a reference region, and clinical studies have not accounted for atrophy-based partial volume effects (PVE). Longitudinal studies using cerebellum as reference tissue have revealed only small mean increases and high inter-subject variability in amyloid binding. We aimed to test the effects of different reference regions and PVE-correction (PVEC) on the discriminatory power and longitudinal performance of amyloid PET. We analyzed [(18)F]-AV45 PET and T1-weighted MRI data of 962 subjects at baseline and two-year follow-up data of 258 subjects. Cortical composite volume-of-interest (VOI) values (COMP) for tracer uptake were generated using either full brain atlas VOIs, gray matter segmented VOIs or gray matter segmented VOIs after VOI-based PVEC. Standard-uptake-value ratios (SUVR) were calculated by scaling the COMP values to uptake in cerebellum (SUVRCBL), brainstem (SUVRBST) or white matter (SUVRWM). Mean SUV, SUVR, and changes after PVEC were compared at baseline between diagnostic groups of healthy controls (HC; N=316), mild cognitive impairment (MCI; N=483) and AD (N=163). Receiver operating characteristics (ROC) were calculated for the discriminations between HC, MCI and AD, and expressed as area under the curve (AUC). Finally, the longitudinal [(18)F]-AV45-PET data were used to analyze the impact of quantitation procedures on apparent changes in amyloid load over time. Reference region SUV was most constant between diagnosis groups for the white matter. PVEC led to decreases of COMP-SUV in HC (-18%) and MCI (-10%), but increases in AD (+7%). Highest AUCs were found when using PVEC with white matter scaling for the contrast between HC/AD (0.907) or with brainstem scaling for the contrast between HC/MCI (0.658). Longitudinal increases were greatest in all diagnosis groups with application of PVEC, and inter-subject variability was lowest for the white matter reference. Thus, discriminatory power of [(18)F]-AV45-PET was improved by use of a VOI-based PVEC and white matter or brainstem rather than cerebellum reference region. Detection of longitudinal amyloid increases was optimized with PVEC and white matter reference tissue.",Aged;Alzheimer Disease/*radionuclide imaging;Amyloid/*analysis;*Aniline Compounds;*Ethylene Glycols;Female;Humans;Male;Mild Cognitive Impairment/*radionuclide imaging;*Positron-Emission Tomography/methods;White Matter/*chemistry/*radionuclide imaging;(18)f-av45-pet;Alzheimer's disease;Partial volume effect correction;Reference region,"Brendel, M.;Hogenauer, M.;Delker, A.;Sauerbeck, J.;Bartenstein, P.;Seibyl, J.;Rominger, A.",2015,Mar,10.1016/j.neuroimage.2014.11.055,0,
5233,Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults,"There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by approximately 88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 +/- 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLU variant was associated with lower fractional anisotropy--a widely accepted measure of white matter integrity--in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.","Adult;Alleles;Alzheimer Disease/genetics/ pathology;Analysis of Variance;Brain/ pathology;Brain Mapping;Clusterin/ genetics;Diffusion Tensor Imaging;Diseases in Twins/genetics/ pathology;Female;Genotype;Humans;Image Processing, Computer-Assisted;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Risk;Twins","Braskie, M. N.;Jahanshad, N.;Stein, J. L.;Barysheva, M.;McMahon, K. L.;de Zubicaray, G. I.;Martin, N. G.;Wright, M. J.;Ringman, J. M.;Toga, A. W.;Thompson, P. M.",2011,May 4,10.1523/jneurosci.5794-10.2011,0,
5234,MR imaging of the aging brain: Patchy White-matter lesions and dementia,"Magnetic resonance (MR) imaging studies of the brain in five elderly patients with non-Alzheimer dementia were compared with those in two groups of nondemented control subjects. Group 1 included five subjects aged 59-66; group 2 included nine subjects aged 74-81. In all of the demented patients and in three of the subjects in the older control group, MR showed diffuse, white-matter lesions. A rating scale was used to grade the severity of the changes. The results suggest a higher incidence of white-matter lesions in elderly patients with non-Alzheimer dementia and in cognitively normal elderly with advancing age.",,"Brant-Zawadzki, M.;Fein, G.;Van Dyke, C.",1985,1985,,0,
5235,Cognitive functioning and brain MRI in patients with type 1 and type 2 diabetes mellitus: A comparative study,"Background/Aims: Diabetes mellitus (DM) may affect the central nervous system, resulting in cognitive impairments. It has been suggested that cognitive impairments are more pronounced in DM2 than in DM1, but studies that directly compare the effects of these 2 types of DM on cognition are lacking. Methods: Forty patients with DM1 (mean duration: 34 years) were compared with 40 age- and education-matched patients who were known to have DM2 (mean duration: 7 years). Extensive neuropsychological assessment focussed on abstract reasoning, memory, attention and executive function, visuoconstruction and information processing speed. Psychological well-being was measured and brain MRIs were obtained. Results: No systematic between-group differences were observed in neuropsychological measures or levels of psychological well-being. DM2 patients showed significantly more deep white matter lesions and cortical atrophy on MRI (p < 0.01). Conclusion: DM1 patients with more than 30 years of DM have a similar cognitive profile and better MRI ratings than age- and education-matched DM2 patients with only 7 years of DM. Copyright © 2007 S. Karger AG.",adult;age;aged;article;attention;brain;brain atrophy;brain damage;clinical article;cognition;controlled study;education;female;human;insulin dependent diabetes mellitus;male;memory;neuropsychological test;non insulin dependent diabetes mellitus;nuclear magnetic resonance imaging;priority journal;wellbeing;white matter,"Brands, A. M. A.;Biessels, G. J.;Kappelle, L. J.;De Haan, E. H. F.;De Valk, H. W.;Algra, A.;Kessels, R. P. C.",2007,,,0,
5236,Brain signature of mild stages of cognitive and behavioral impairment in amyotrophic lateral sclerosis,"We aimed to assess the brain signature of cognitive and behavioral impairment in C9orf72-negative non-demented ALS patients. The study included 50 amyotrophic lateral sclerosis (ALS) patients (out of 75 initially recruited) and 38 healthy controls. High-resolution T1-weighted and spin-echo diffusion tensor images were acquired in a 3T MRI scanner. The multi atlas-based analysis protocol and the FreeSurfer tool were employed for gray matter assessment, and fiber tractography for white matter evaluation. Cognitively impaired ALS patients (n = 12) had bilateral amygdalae and left thalamic volumetric reduction compared to non-impaired ALS patients. Behaviorally impaired ALS patients (n = 14) had lower fractional anisotropy (FA) at the fornix in comparison with healthy subjects. These parameters did correlate with cognitive/behavioral scores, but not with motor-functional parameters in the ALS cohort. We believe that basal ganglia and fornix damage might be related to cognitive and behavioral impairment across ALS-frontotemporal dementia continuum. Also, distinct anatomical areas seem to influence the behavioral and cognitive status of these individuals.",Amyotrophic lateral sclerosis;Cognition;FreeSurfer;Magnetic resonance imaging;Multi-atlas based analysis,"Branco, L. M. T.;de Rezende, T. J. R.;Roversi, C. O.;Zanao, T.;Casseb, R. F.;de Campos, B. M.;Franca, M. C., Jr.",2018,Feb 28,,0,
5237,Longitudinal gray matter contraction in three variants of primary progressive aphasia: A tenser-based morphometry study,"The present study investigated the pattern of longitudinal changes in cognition and anatomy in three variants of primary progressive aphasia (PPA). Eight patients with the non-fluent variant of PPA (nfvPPA), 13 patients with the semantic variant (svPPA), seven patients with the logopenic variant (lvPPA), and 29 age-matched, neurologically healthy controls were included in the study. All participants underwent longitudinal MRI, neuropsychological and language testing at baseline and at a 1-year follow-up. Tenser-based morphometry (TBM) was applied to T1-weighted MRI images in order to map the progression of gray and white matter atrophy over a 1-year period. Results showed that each patient group was characterized by a specific pattern of cognitive and anatomical changes. Specifically, nfvPPA patients showed gray matter atrophy progression in the left frontal and subcortical areas as well as a decline in motor speech and executive functions; svPPA patients presented atrophy progression in the medial and lateral temporal lobe and decline in semantic memory abilities; and lvPPA patients showed atrophy progression in lateral/posterior temporal and medial parietal regions with a decline in memory, sentence repetition and calculations. In addition, in all three variants, the white matter fibers underlying the abovementioned cortical areas underwent significant volume contraction over a 1-year period. Overall, these results indicate that the three PPA variants present distinct patterns of neuroanatomical contraction, which reflect their clinical and cognitive progression.","Aged;Aphasia, Primary Progressive/ pathology/physiopathology;Atrophy/pathology;Disease Progression;Executive Function/ physiology;Female;Follow-Up Studies;Gray Matter/ pathology;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Primary Progressive Nonfluent Aphasia/pathology/physiopathology","Brambati, S. M.;Amici, S.;Racine, C. A.;Neuhaus, J.;Miller, Z.;Ogar, J.;Dronkers, N.;Miller, B. L.;Rosen, H.;Gorno-Tempini, M. L.",2015,,10.1016/j.nicl.2015.01.011,0,
5238,Structural brain correlates of anterograde memory deficits in multiple sclerosis,"Progressive decline of anterograde memory functions has been increasingly recognized as a frequent symptom in chronic multiple sclerosis. In order to investigate the brain structures involved, magnetic resonance imaging was performed in 20 patients. Neuropsychological assessment included the WAIS and WMS subtests information, picture completion, similarities, digit span, logical memory, and paired associate learning. All patients with severely impaired memory functions (n = 5) showed bilateral lesions in the medial temporal lobe, whereas in those patients with moderate (n = 10) or no measurable impairment of memory testing (n = 5) either no lesions were seen in the medial temporal lobes or these lesions were restricted to one side. A post hoc cluster analysis strikingly confirmed these results. The differences could not be related to the age of the patients, the disease duration, or the level of education. Extensive lesions in the white matter of the frontal lobes, thinning and lining of the corpus callosum, and bilateral involvement of the anterior cingulate gyrus had no bearing on the neuropsychological results. These findings indicate that bilateral demyelination in the hippocampal regions is the most likely explanation for the impairment of anterograde memory in such patients.",,"Brainin, M.;Goldenberg, G.;Ahlers, C.;Reisner, T.;Neuhold, A.;Deecke, L.",1988,1988,,0,
5239,Computed tomography in the investigation of dementia,"To assess the value of computed tomography in investigating patients with dementia, 500 consecutive patients presenting with a provisional clinical diagnosis of dementia of recent onset were reviewed and the results analysed in a computer. Most patients had either cerebral atrophy or infarction, but 82 patients had a normal scan and 42 others had tumours. More than 10% of all patients, including 5% with no other symptoms or signs, had a treatable lesion. Various associated symptoms and signs were useful pointers to such a treatable lesion and clearly indicated computed tomography. Accurate diagnosis is the cornerstone of proper management, and if a few patients with treatable lesions can be identified then the benefits to all concerned may be incalculable.",aged;brain atrophy;brain infarction;brain tumor;central nervous system;computer analysis;computer assisted tomography;dementia;diagnosis;human;major clinical study,"Bradshaw, J. R.;Thomson, J. L. G.;Campbell, M. J.",1983,,,0,
5240,Association of deep white matter infarction with chronic communicating hydrocephalus: implications regarding the possible origin of normal-pressure hydrocephalus,"The coexistence of cerebrovascular disease leading to deep white matter infarction and normal-pressure hydrocephalus has been noted previously in clinical studies, as both diseases can present with the triad of gait disturbance, dementia, and incontinence. The purpose of this MR study was to determine if the two diseases demonstrated a statistical association. Evidence of patchy periventricular hyperintensity representing presumed deep white matter infarction was sought in 20 patients shunted for normal-pressure hydrocephalus and in 35 additional consecutive patients with clinical symptoms and MR findings consistent with normal-pressure hydrocephalus. Deep white matter infarction was also sought in 62 consecutive age-matched control subjects. There was a statistically significant (p less than .001) higher association (58%) of marked infarction in the 55 patients with normal-pressure hydrocephalus than in the age-matched controls (24%). MR findings of communicating hydrocephalus (ventriculomegaly and increased aqueductal CSF flow void) were sought in 78 consecutive patients with presumed deep white matter infarction, and the degree of severity of the two diseases was also found to be statistically significant (p less than .05). In view of this association, the possibility that the two diseases are related was considered. A potential mechanism is discussed whereby deep white matter infarction leading to decreased periventricular tensile strength could result in communicating hydrocephalus. It is plausible that normal-pressure hydrocephalus may result from a number of different insults to the brain.","Aged;Cerebral Infarction/*complications/diagnosis;Humans;Hydrocephalus, Normal Pressure/diagnosis/*etiology;Magnetic Resonance Imaging","Bradley, W. G., Jr.;Whittemore, A. R.;Watanabe, A. S.;Davis, S. J.;Teresi, L. M.;Homyak, M.",1991,Jan-Feb,,0,
5241,Marked cerebrospinal fluid void: indicator of successful shunt in patients with suspected normal-pressure hydrocephalus,"The authors blindly reviewed the charts of 20 patients with normal-pressure hydrocephalus (a disease of unknown cause characterized radiologically as chronic communicating hydrocephalus and clinically by gait apraxia, dementia, and incontinence) who had undergone creation of a ventriculoperitoneal shunt. The initial clinical response to surgery was graded excellent, good, fair, or poor; 5-year follow-up was available in 55% of cases. The magnetic resonance (MR) images obtained in these patients were also blindly reviewed for the magnitude of cerebrospinal fluid (CSF) flow void (graded on the basis of extent rather than degree of signal loss) in the cerebral aqueduct. A significant (P less than .003) correlation existed between good or excellent response to surgery and an increased CSF flow void. The presence of associated deep white matter infarction on MR images did not correlate with a poor response to surgery. On the basis of these findings, it is suggested that patients who fulfill the clinical criteria of NPH and have an increased CSF flow void undergo creation of a shunt.","Aged;Aged, 80 and over;Brain/pathology;Cerebral Aqueduct/pathology;Cerebrospinal Fluid/ physiology;Cerebrospinal Fluid Shunts;Female;Follow-Up Studies;Humans;Hydrocephalus, Normal Pressure/diagnosis/ physiopathology/surgery;Magnetic Resonance Imaging;Male;Middle Aged","Bradley, W. G., Jr.;Whittemore, A. R.;Kortman, K. E.;Watanabe, A. S.;Homyak, M.;Teresi, L. M.;Davis, S. J.",1991,Feb,10.1148/radiology.178.2.1987609,0,
5242,Magnetic Resonance Imaging of Normal Pressure Hydrocephalus,"Normal pressure hydrocephalus (NPH) is a syndrome found in the elderly, which is characterized by ventriculomegaly and deep white matter ischemia (DWMI) on magnetic resonance imaging (MRI) and the clinical triad of gait disturbance, dementia, and urinary incontinence. NPH has been estimated to account for up to 10% of cases of dementia and is significant because it is treatable by ventriculoperitoneal shunting. Patients with a known cause of chronic communicating hydrocephalus, that is, meningitis or hemorrhage, tend to respond better than patients with the so-called ""idiopathic"" form, most likely because of poor selection criteria in the past. Good response to shunting has been associated with hyperdynamic cerebrospinal fluid (CSF) flow through the aqueduct. In the early days of MRI, patients with a large CSF flow void extending from the foramen of Monro through the aqueduct to the fourth ventricle had an excellent chance of responding to ventriculoperitoneal shunting (P < 0.003). Today, we use phase-contrast MRI to measure the volume of CSF flowing through the aqueduct in either direction over a cardiac cycle. When this aqueductal CSF stroke volume is sufficiently elevated, there is an excellent chance of shunt responsiveness (100% positive predictive value in 1 study). Idiopathic NPH appears to be a ""two-hit"" disease-benign external hydrocephalus (BEH) in infancy followed by DWMI in late adulthood. As BEH occurs when the sutures are still open, these infants present with large heads, a finding also noted in patients with NPH. Although BEH has been attributed to immature arachnoidal granulations with decreased CSF resorptive capacity, this now appears to be permanent and may lead to a parallel pathway for CSF resorption via the extracellular space of the brain. With DWMI, the myelin lipid is lost, exposing the polar water molecules to myelin protein, increasing resistance to CSF outflow and leading to backing up of CSF and hydrocephalus.",,"Bradley, W. G., Jr.",2016,Apr,10.1053/j.sult.2016.01.005,0,
5243,"Idiopathic normal pressure hydrocephalus may be a ""two hit"" disease: Benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood","Purpose: To determine if normal pressure hydrocephalus (NPH) could result from decreased resorption of cerebrospinal fluid (CSF) by the arachnoidal villi, leading to benign external hydrocephalus [BEH] in infancy, followed by deep white matter ischemia (DWMI) in late adulthood (the more hydrophilic environment increasing resistance to CSF flow through the extracellular space (ECS) of the brain). Materials and Methods: CSF outflow via the fourth ventricle and the ECS of the brain was mathematically modeled using a parallel electrical circuit analog. The apparent diffusion coefficient (ADC) was measured as a surrogate of the amount of water in the ECS in normals, patients with symptomatic NPH, and patients with dilated ventricles without symptoms of NPH (""pre-NPH""). Results: The electrical circuit model demonstrates increasing ventricular volume with increasing resistance to flow through the ECS of the brain. ADC measurements performed in the centrum semiovale are significantly higher in patients with NPH and ""pre-NPH"" than in age-matched controls (P < 0.05), controlling for the same degree of DWMI indicating increased fluid in the ECS of the brain. Conclusion: The electrical circuit analog and finding of increased periventricular ADC support the theory that NPH is a ""two hit"" disease. © 2006 Wiley-Liss, Inc.",adult;adulthood;aged;article;benign external hydrocephalus;brain arachnoid;brain electrophysiology;brain fourth ventricle;brain ischemia;brain ventricle dilatation;cerebrospinal fluid flow;controlled study;diffusion coefficient;disease association;electric current;electric model;extracellular space;female;human;hydrophilicity;infancy;major clinical study;male;mathematical model;normotensive hydrocephalus;priority journal;water content;white matter;EchoSpeed;Matlab v6.5.1;SPSS version 12.0.1,"Bradley Jr, W. G.;Bahl, G.;Alksne, J. F.",2006,,,0,
5244,Alzheimer's disease: role of size and location of white matter changes in determining cognitive deficits,"This study investigated the contribution that white matter changes (WMCs) make to clinical and cognitive features in Alzheimer's disease (AD), independently of possible confounders such as cortical atrophy and the apolipoprotein E genotype as well as their relationship to vascular risk factors. We semiquantitatively assessed the degree and location of WMCs (global, periventricular and deep white matter), lacunes and global atrophy on brain MRI scans of 86 AD cases, extensively evaluated from a clinical and neuropsychological point of view. Multivariate logistic and linear regression analysis showed that age was the only significant predictor of all WMC measures and revealed a significant association of periventricular WMCs with performance on executive function tasks as well as of deep WMCs with history of mood depression. Our results underline the significance of WMC location over size in the occurrence of specific cognitive deficits in AD.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/*psychology;Analysis of Variance;Apolipoproteins E/analysis;Brain/*pathology;Cognition Disorders/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Bracco, L.;Piccini, C.;Moretti, M.;Mascalchi, M.;Sforza, A.;Nacmias, B.;Cellini, E.;Bagnoli, S.;Sorbi, S.",2005,,10.1159/000088562,0,
5245,Relation between MRI features and dementia in cerebrovascular disease patients with leukoaraiosis: a longitudinal study,"We examined selective MRI features (localization and degree of white matter abnormalities, cortical and subcortical atrophy) in relation to cognitive decline in patients with cerebrovascular disease (CVD) and leukoaraiosis (LA). We enrolled 6 female and 18 male CVD patients (mean age 66.2 +/- 6.6 years) whose Magnetic Resonance Images (MRI) revealed LA and who displayed a history of stroke or TIA; none showed signs of cortical infarcts or normal pressure hydrocephalus. Two blind raters independently scored MRI scans with a high level of agreement. All patients underwent extensive clinico-neuropsychological assessment upon admission to the study and 19 were followed for an average of 48 +/- 7.6 months. Twelve patients were initially classified as non-demented and 12 as demented. Three years later, one in the former group had become demented and mental impairment had worsened for 6 patients in the latter group; these 7 subjects were labeled as ""decliners"". Ventricular indexes were significantly higher in the demented group and correlated with severity of mental impairment, while the degree of LA was similar in demented and non-demented subjects. Neither white matter lesions nor sulcal and ventricular enlargement differed statistically between decliners and non-decliners.","Aged;Atrophy/pathology;Cerebral Cortex/ pathology;Cerebrovascular Disorders/ pathology/ psychology;Cognition Disorders/pathology/psychology;Dementia/ pathology/ psychology;Female;Humans;Ischemic Attack, Transient/pathology/psychology;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests","Bracco, L.;Campani, D.;Baratti, E.;Lippi, A.;Inzitari, D.;Pracucci, G.;Amaducci, L.",1993,Dec 15,,0,
5246,Diffusion and perfusion MR imaging in cases of Alzheimer's disease: correlations with cortical atrophy and lesion load,"BACKGROUND AND PURPOSE: Perfusion and diffusion-weighted MR imaging are powerful new imaging techniques for evaluating tissue pathophysiology in association with many neurologic disorders, such as neurodegenerative diseases. The purpose of our study was to evaluate the sensitivity and specificity of dynamic susceptibility contrast-enhanced MR imaging and diffusion-weighted MR imaging in cases of Alzheimer's disease and to assess the role of atrophy in the quantification of cortical perfusion. METHODS: Thirty-nine participants were studied: 18 patients with moderate cognitive impairment with probable Alzheimer's disease, 16 patients with mild impairment with possible or probable Alzheimer's disease, and 15 group-matched elderly healthy comparison volunteers. Relative values of temporoparietal, sensorimotor, and hippocampal regional cerebral blood volume (rCBV) were measured as a percentage of cerebellar rCBV, and group classification was assessed with logistic regression. Brain atrophy was used as a covariate to assess its role in rCBV quantification. Regions of interest placed on orientation-independent apparent diffusion coefficient maps allowed the calculation of apparent diffusion coefficient values and relative anisotropic indices of the head of the caudate nuclei, thalamus, parietal, frontal, and hippocampal cortices bilaterally, genu and splenium of corpus callosum, and anterior and posterior white matter in patients with Alzheimer's disease and in control volunteers. RESULTS: Temporoparietal rCBV ratios were reduced bilaterally in the patients with Alzheimer's disease. Sensitivity was 91% in moderately affected patients with Alzheimer's disease and 90% in patients with mild cases. Specificity was 87% in healthy comparison volunteers. Lower values of sensitivity and specificity were obtained for sensorimotor (73%, 50%, and 67%, respectively) and hippocampal cortices (80%, 80%, and 65%, respectively). Using brain atrophy as a covariate, patients with Alzheimer's disease still showed a statistically significant reduction of rCBV compared with control volunteers. Diffusion-weighted MR imaging analysis only showed a trend, with no statistic significance, of reduction of anisotropy in posterior white matter. CONCLUSION: Dynamic susceptibility contrast-enhanced MR imaging of rCBV may be an alternative to nuclear medicine imaging for the evaluation of patients with Alzheimer's disease. When brain atrophy is used as a covariate, differences in rCBV still persist between patients with Alzheimer's disease and control volunteers, suggesting that perfusion impairment is unrelated to atrophy. No significant results for either white or gray matter were obtained using diffusion-weighted MR imaging.","Aged;Alzheimer Disease/ diagnosis/physiopathology;Anisotropy;Atrophy;Brain/blood supply/pathology;Cerebral Cortex/ pathology/physiopathology;Diagnosis, Differential;Diffusion;Disease Susceptibility/diagnosis/physiopathology;Dominance, Cerebral/physiology;Female;Humans;Image Enhancement;Magnetic Resonance Imaging;Male;Middle Aged;Reference Values;Regional Blood Flow/physiology","Bozzao, A.;Floris, R.;Baviera, M. E.;Apruzzese, A.;Simonetti, G.",2001,Jun-Jul,,0,
5247,Quantitative MRI to understand Alzheimer's disease pathophysiology,"PURPOSE OF REVIEW: The role of white matter damage in the progression of Alzheimer's disease and the associated cognitive symptoms is becoming increasingly clearer. This is partly because of the advent of diffusion tensor imaging, which, in combination with other quantitative MRI techniques, offers unique insights into the patholophysiology of Alzheimer's disease in vivo. The purpose of this review is to integrate the most recent imaging findings, with respect to understanding Alzheimer's disease pathophysiology, and identifying potential biomarkers with diagnostic and prognostic value. RECENT FINDINGS: Consistent with patterns of gray matter atrophy, white matter damage in Alzheimer's disease is localized within white matter tracts connecting the temporal lobe with the rest of the brain, including the cingulum, the uncinate fasciculus and the fornix. These abnormalities are often correlated with adjacent gray matter tissue loss, and with cognitive performance. The relationship between these findings and loss of functional connectivity supports the hypothesis of disconnection as a mechanism for the spread of Alzheimer's disease. SUMMARY: White matter abnormalities occur early in Alzheimer's disease, and might actively contribute to the progression of the disease. Functional and structural gray matter abnormalities parallel the white matter changes, and successful biomarkers are likely to be multiparametric.",,"Bozzali, M.;Serra, L.;Cercignani, M.",2016,Aug,10.1097/wco.0000000000000345,0,
5248,Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease,"A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naive) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement.","Aged;Aged, 80 and over;Alzheimer Disease/complications/*drug therapy/*pathology;Antipsychotic Agents/pharmacology/*therapeutic use;Brain/*drug effects;Brain Mapping;Cholinesterase Inhibitors/pharmacology/*therapeutic use;Cognition Disorders/drug therapy/etiology;Diffusion Magnetic Resonance Imaging;Female;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Statistics as Topic;AChE inhibitor;Alzheimer disease;anatomical connectivity mapping;brain plasticity;diffusion MRI","Bozzali, M.;Parker, G. J.;Spano, B.;Serra, L.;Giulietti, G.;Perri, R.;Magnani, G.;Marra, C.;M, G. Vita;Caltagirone, C.;Cercignani, M.",2013,Dec,10.1002/hbm.22130,0,
5249,Regional grey matter loss and brain disconnection across Alzheimer disease evolution,"It is becoming increasingly clearer that the clinical manifestations of Alzheimer's disease (AD) are not only associated with regional grey matter (GM) damage, but also with abnormal integration between cortical brain regions by disconnection mechanism. This concept comes from the evidence that white matter (WM) damage (as assessed by diffusion MR imaging) can be observed in patients with AD since the early clinical stages, and it correlates with clinical measures of cognitive disability. In this perspective, several functional imaging studies, based on PET and resting state fMRI, have provided evidence that brain hypometabolism/disconnection may precede the occurrence of GM atrophy in certain regions of AD brains, such as the cingulate cortex. The cingulum represents the most prominent WM tract of the limbic system, being directly connected to the medial temporal lobe structures. Therefore, this structure likely contributes to changes in functional connectivity observed within the so called default-mode network of AD patients, and its damage is likely to play a remarkable role in the conversion from mild cognitive impairment (MCI) to dementia. Nowadays, the combination of several neuroimaging techniques that provide both, measures of regional GM loss and measures of functional and structural connectivity offer the opportunity to investigate in vivo the pathophysiological changes of brain tissue modifications across the clinical evolution of AD. This paper reviews the main MR based methods of investigation of brain tissue involvement in patients with AD and MCI, and the role they have played in clarifying the differential contribution of GM damage and brain disconnection to AD pathophysiology. This subject seems to be relevant for both, speculative aspects of neurology and application to clinical trials. © 2011 Bentham Science Publishers Ltd.",,"Bozzali, M.;Padovani, A.;Caltagirone, C.;Borroni, B.",2011,June,,0,
5250,Damage to the cingulum contributes to Alzheimer's disease pathophysiology by deafferentation mechanism,"This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimer's disease (AD). Thirty-one patients with probable AD, 23 with amnestic mild cognitive impairment (a-MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel-based morphometry was used to assess regional GM atrophy in AD and a-MCI patients. Diffusion tensor-MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel-by-voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a-MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro- and (to a lesser extent) macroscopic damage of patients' cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients' measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD.","Aged;Aged, 80 and over;Alzheimer Disease/*pathology/physiopathology;Atrophy/pathology/physiopathology;Diffusion Tensor Imaging;Disease Progression;Female;Gyrus Cinguli/*pathology/physiopathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/pathology/physiopathology;Nerve Fibers, Myelinated/*pathology;Nerve Fibers, Unmyelinated/*pathology","Bozzali, M.;Giulietti, G.;Basile, B.;Serra, L.;Spano, B.;Perri, R.;Giubilei, F.;Marra, C.;Caltagirone, C.;Cercignani, M.",2012,Jun,10.1002/hbm.21287,0,
5251,White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging,"OBJECTIVE: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimer's disease using diffusion tensor magnetic resonance imaging (DT-MRI). BACKGROUND: Although Alzheimer's disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimer's disease associated white matter damage is still unclear. METHODS: Conventional and DT-MRI scans were obtained from 16 patients with Alzheimer's disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. RESULTS: D was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding regions from healthy controls. D and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D (r=0.92, p<0.001) and FA (r=0.78; p<0.001). CONCLUSIONS: White matter changes in patients with Alzheimer's disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.","Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology;Cerebral Cortex/ pathology;Corpus Callosum/pathology;Female;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged","Bozzali, M.;Falini, A.;Franceschi, M.;Cercignani, M.;Zuffi, M.;Scotti, G.;Comi, G.;Filippi, M.",2002,Jun,,0,
5252,Brain tissue damage in dementia with Lewy bodies: an in vivo diffusion tensor MRI study,"The aim of the present study was to apply diffusion tensor MRI (DT-MRI), a quantitative MRI measure which reflects tissue organization, to dementia with Lewy bodies (DLB). DT-MRI scans were obtained from 15 patients with probable DLB and 10 sex- and age-matched healthy controls. Abnormalities were found in the corpus callosum, pericallosal areas and the frontal, parietal, occipital and, less prominently, temporal white matter of patients compared with controls. Abnormalities were also found in the caudate nucleus and the putamen. The average grey matter volume was lower in patients than in controls. These findings of concomitant grey matter atrophy and white matter abnormalities (as detected by DT-MRI) in regions with a high prevalence of long connecting fibre tracts might suggest the presence of neurodegeneration involving associative cortices. The modest involvement of the temporal lobe fits with the relative preservation of global neuropsychological measures and memory tasks in the early stage of DLB. The selective involvement of parietal, frontal and occipital lobes might explain some of the clinical and neuropsychological features of DLB, providing a possible distinctive marker for this disease. The abnormalities found in the subcortical grey matter may indicate that DLB and Parkinson's disease share a similar nigrostriatal involvement caused by common pathophysiological mechanisms.","Aged;Aged, 80 and over;Brain/*pathology;Case-Control Studies;Caudate Nucleus/pathology;Diffusion Magnetic Resonance Imaging/*methods;Female;Humans;Lewy Body Disease/*pathology/psychology;Linear Models;Male;Neuropsychological Tests;Putamen/pathology;Temporal Lobe/pathology","Bozzali, M.;Falini, A.;Cercignani, M.;Baglio, F.;Farina, E.;Alberoni, M.;Vezzulli, P.;Olivotto, F.;Mantovani, F.;Shallice, T.;Scotti, G.;Canal, N.;Nemni, R.",2005,Jul,10.1093/brain/awh493,0,
5253,Structural brain signature of FTLD driven by Granulin mutation,"Several causative gene mutations have been identified in frontotemporal lobar degeneration (FTLD), including mutations within Granulin (GRN) genes. It was recently shown that FTLD patients carriers of GRN Thr272fs mutation [FTLD-GRN(m+)] exhibit more severe abnormalities, as assessed by magnetic resonance imaging (MRI), than those with sporadic FTLD [FTLD-GRN(m-)]. The aim of this study was to investigate the relationship between grey (GM) and white matter (WM) microstructural damage in FTLD patients, carriers and non-carriers of the mutation. Twenty-three FTLD patients [6 GRN(m+) and 17 GRN(m-)] and 12 healthy subjects received an MRI scan including volumetric and diffusion imaging. GM was assessed using voxel-based morphometry, while the corpus callosum was reconstructed using diffusion tractography. Mean diffusivity and fractional anisotropy of the corpus callosum were compared between groups. FTLD patients showed widespread GM atrophy and altered diffusion indices in the corpus callosum when compared to healthy subjects. When contrasting GRN(m+) against GRN(m-) patients, the former group had more atrophy in the left frontal GM, and reduced fractional anisotropy and increased mean diffusivity in the left anterior part of the corpus callosum. Significant correlations between the GM and WM damage were found in GRN(m+) patients. This pattern of damage was able to predict some of the additional neuropsychological deficits observed in GRN(m+) as compared to GRN(m-) patients. A more prominent involvement of WM in GRN(m+) patients is consistent with the knowledge that GRN genes are expressed in the microglia. This involvement might be responsible for the accrual of additional GM atrophy via disconnection mechanisms.",Aged;Atrophy/genetics/pathology;Brain/ pathology;Corpus Callosum/ pathology;Diffusion Tensor Imaging;Female;Frontotemporal Lobar Degeneration/ genetics/ pathology;Humans;Intercellular Signaling Peptides and Proteins/ genetics;Magnetic Resonance Imaging;Male;Microglia/pathology;Middle Aged;Neurons/pathology;Neuropsychological Tests;Point Mutation;Predictive Value of Tests,"Bozzali, M.;Battistoni, V.;Premi, E.;Alberici, A.;Giulietti, G.;Archetti, S.;Turla, M.;Gasparotti, R.;Cercignani, M.;Padovani, A.;Borroni, B.",2013,,10.3233/jad-2012-121273,0,
5254,Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer's disease: a DTI/FDG-PET study,"BACKGROUND: Alzheimer's disease (AD) and mild cognitive impairment (MCI) affect the limbic system, causing medial temporal lobe (MTL) atrophy and posterior cingulate cortex (PCC) hypometabolism. Additionally, diffusion tensor imaging (DTI) studies have demonstrated that MCI and AD involve alterations in cerebral white matter (WM) integrity. OBJECTIVES: To test if (1) patients with MCI and AD exhibit decreases in the integrity of limbic WM pathways; (2) disconnection between PCC and MTL, manifested as disruption of the cingulum bundle, contributes to PCC hypometabolism during incipient AD. METHODS: We measured fractional anisotropy (FA) and volume of the fornix and cingulum using DTI in 23 individuals with MCI, 21 with mild-to-moderate AD, and 16 normal control (NC) subjects. We also measured PCC metabolism using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in AD and MCI patients. RESULTS: Fornix FA and volume were reduced in MCI and AD to a similar extent. Descending cingulum FA was reduced in AD while volume was reduced in MCI and even more so in AD. Both FA and volume of the fornix and descending cingulum reliably discriminated between NC and AD. Fornix FA and descending cingulum volume also reliably discriminated between NC and MCI. Only descending cingulum volume reliably discriminated between MCI and AD. In the combined MCI-AD cohort, PCC metabolism directly correlated with both FA and volume of the descending cingulum. CONCLUSIONS: Disruption of limbic WM pathways is evident during both MCI and AD. Disconnection of the PCC from MTL at the cingulum bundle contributes to PCC hypometabolism during incipient AD.","Aged;Alzheimer Disease/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Humans;Image Interpretation, Computer-Assisted;Male;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology;Neural Pathways/ pathology;Positron-Emission Tomography","Bozoki, A. C.;Korolev, I. O.;Davis, N. C.;Hoisington, L. A.;Berger, K. L.",2012,Aug,10.1002/hbm.21320,0,
5255,Posterior cerebral artery infarction with cognitive findings: More than hemianopia,"Posterior cerebral artery infarctions constitute 5-10% of all ischemic strokes. The case of a 62 year-old man presenting with right hemiparesia and dysarthria is discussed in this article. The patient had acute onset demential symptoms and difficulty in reading, and an acute infarction in the territory of left posterior cerebral artery was detected in cranial magnetic resonance imaging. The patient who had acute ischemic lesions in left parahippocampus, splenium of corpus callosum, left fusiform gyrus and left thalamus was evaluated with detailed neuropsychological tests. Cognitive deficits severe enough to affect daily living were detected. Pure alexia, anterograde amnesia and anomia, being often neglected manifestations of unilateral posterior cerebral artery infarction, are going to be reviewed with relevant radiological findings.",,"Bozdoǧan, Z.;Taşkiran Saǧ, A.;Neşe Öztekin, Z.;Ak, F.",2013,2013,,0,
5256,Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils,"Measures of structural brain change based on longitudinal MR imaging are increasingly important but can be degraded by intensity non-uniformity. This non-uniformity can be more pronounced at higher field strengths, or when using multichannel receiver coils. We assessed the ability of the non-parametric non-uniform intensity normalization (N3) technique to correct non-uniformity in 72 volumetric brain MR scans from the preparatory phase of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Normal elderly subjects (n=18) were scanned on different 3-T scanners with a multichannel phased array receiver coil at baseline, using magnetization prepared rapid gradient echo (MP-RAGE) and spoiled gradient echo (SPGR) pulse sequences, and again 2 weeks later. When applying N3, we used five brain masks of varying accuracy and four spline smoothing distances (d=50, 100, 150 and 200 mm) to ascertain which combination of parameters optimally reduces the non-uniformity. We used the normalized white matter intensity variance (standard deviation/mean) to ascertain quantitatively the correction for a single scan; we used the variance of the normalized difference image to assess quantitatively the consistency of the correction over time from registered scan pairs. Our results showed statistically significant (p<0.01) improvement in uniformity for individual scans and reduction in the normalized difference image variance when using masks that identified distinct brain tissue classes, and when using smaller spline smoothing distances (e.g., 50-100 mm) for both MP-RAGE and SPGR pulse sequences. These optimized settings may assist future large-scale studies where 3-T scanners and phased array receiver coils are used, such as ADNI, so that intensity non-uniformity does not influence the power of MR imaging to detect disease progression and the factors that influence it.","Aged;Algorithms;Alzheimer Disease/ pathology;Brain/pathology;Calibration;Cognition Disorders/pathology;Data Interpretation, Statistical;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/ instrumentation;Reproducibility of Results","Boyes, R. G.;Gunter, J. L.;Frost, C.;Janke, A. L.;Yeatman, T.;Hill, D. L.;Bernstein, M. A.;Thompson, P. M.;Weiner, M. W.;Schuff, N.;Alexander, G. E.;Killiany, R. J.;DeCarli, C.;Jack, C. R.;Fox, N. C.",2008,Feb 15,10.1016/j.neuroimage.2007.10.026,0,
5257,Brain microbleeds: Epidemiology and clinical implications Microhemorragias cerebrales: epidemiologia e implicaciones clinicas,"INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process.",Alzheimer disease;Angiopatia amiloide cerebral;Brain microbleeds;Cerebral amyloid angiopathy;Cerebrovascular disease;Cognitive impairment;Deterioro cognitivo;Enfermedad cerebrovascular;Enfermedad de Alzheimer;Lipohialinosis;Lipohyalinosis;Microhemorragias cerebrales,"Boyano, I.;Bravo, N.;Miranda, J.;Gil-Gregorio, P.;Olazaran, J.",2016,Jun 22,,0,
5258,Brain microbleeds: Epidemiology and clinical implications,"INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process.",Alzheimer disease;Angiopatia amiloide cerebral;Brain microbleeds;Cerebral amyloid angiopathy;Cerebrovascular disease;Cognitive impairment;Deterioro cognitivo;Enfermedad cerebrovascular;Enfermedad de Alzheimer;Lipohialinosis;Lipohyalinosis;Microhemorragias cerebrales,"Boyano, I.;Bravo, N.;Miranda, J.;Gil-Gregorio, P.;Olazaran, J.",2016,Jun 22,10.1016/j.nrl.2016.04.016,0,
5259,Extrastriatal changes in patients with late-onset glutaric aciduria type I highlight the risk of long-term neurotoxicity,"BACKGROUND: Without neonatal initiation of treatment, 80-90% of patients with glutaric aciduria type 1 (GA1) develop striatal injury during the first six years of life resulting in a complex, predominantly dystonic movement disorder. Onset of motor symptoms may be acute following encephalopathic crisis or insidious without apparent crisis. Additionally, so-called late-onset GA1 has been described in single patients diagnosed after the age of 6 years. With the aim of better characterizing and understanding late-onset GA1 we analyzed clinical findings, biochemical phenotype, and MRI changes of eight late-onset patients and compared these to eight control patients over the age of 6 years with early diagnosis and start of treatment. RESULTS: No late-onset or control patient had either dystonia or striatal lesions on MRI. All late-onset (8/8) patients were high excretors, but only four of eight control patients. Two of eight late-onset patients were diagnosed after the age of 60 years, presenting with dementia, tremor, and epilepsy, while six were diagnosed before the age of 30 years: Three were asymptomatic mothers identified by following a positive screening result in their newborns and three had non-specific general symptoms, one with additional mild neurological deficits. Frontotemporal hypoplasia and white matter changes were present in all eight and subependymal lesions in six late-onset patients. At comparable age a greater proportion of late-onset patients had (non-specific) clinical symptoms and possibly subependymal nodules compared to control patients, in particular in comparison to the four clinically and MR-wise asymptomatic low-excreting control patients. CONCLUSIONS: While clinical findings are non-specific, frontotemporal hypoplasia and subependymal nodules are characteristic MRI findings of late-onset GA1 and should trigger diagnostic investigation for this rare disease. Apart from their apparent non-susceptibility for striatal injury despite lack of treatment, patients with late-onset GA1 are not categorically different from early treated control patients. Differences between late-onset patients and early treated control patients most likely reflect greater cumulative neurotoxicity in individuals remaining undiagnosed and untreated for years, even decades as well as the higher long-term risk of high excretors for intracerebral accumulation of neurotoxic metabolites compared to low excretors.","EC 1.3.8.6 (Glutaryl-CoA Dehydrogenase);Glutaric Acidemia I;Adult;Amino Acid Metabolism, Inborn Errors/ pathology;Brain Diseases, Metabolic/ pathology;Dystonia/pathology;Female;Glutaryl-CoA Dehydrogenase/ deficiency;Humans;Infant, Newborn;Magnetic Resonance Imaging;Male;Middle Aged;Frontotemporal hypoplasia;Glutaric aciduria type I;High excretor;Late-onset;Long-term disease course;Subependymal nodules","Boy, N.;Heringer, J.;Brackmann, R.;Bodamer, O.;Seitz, A.;Kolker, S.;Harting, I.",2017,Apr 24,,0,
5260,"Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family","Background: Frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) is a heritable form of FTD, but the gene(s) responsible for the majority of autosomal dominant FTD-ALS cases have yet to be found. Previous studies have identified a region on chromosome 9p that is associated with FTD and ALS. Methods: The authors report the clinical, volumetric MRI, neuropathological and genetic features of a new chromosome 9p-linked FTD-ALS family, VSM-20. Results: Ten members of family VSM-20 displayed heterogeneous clinical phenotypes of isolated behavioural-variant FTD (bvFTD), ALS or a combination of the two. Parkinsonism was common, with one individual presenting with a corticobasal syndrome. Analysis of structural MRI scans from five affected family members revealed grey- and white-matter loss that was most prominent in the frontal lobes, with mild parietal and occipital lobe atrophy, but less temporal lobe atrophy than in 10 severity-matched sporadic bvFTD cases. Autopsy in three family members showed a consistent and unique subtype of FTLD-TDP pathology. Genome-wide linkage analysis conclusively linked family VSM-20 to a 28.3 cM region between D9S1808 and D9S251 on chromosome 9p, reducing the published minimal linked region to a 3.7 Mb interval. Genomic sequencing and expression analysis failed to identify mutations in the 10 known and predicted genes within this candidate region, suggesting that next-generation sequencing may be needed to determine the mutational mechanism associated with chromosome 9p-linked FTD-ALS. Conclusions: Family VSM-20 significantly reduces the region linked to FTD-ALS on chromosome 9p. A distinct pattern of brain atrophy and neuropathological findings may help to identify other families with FTD-ALS caused by this genetic abnormality.",adult;amyotrophic lateral sclerosis;article;chromosome 9p;clinical article;clinical feature;corticobasal degeneration;disease association;female;frontal lobe;frontal variant frontotemporal dementia;gene sequence;genetic association;gray matter;human;male;neuroimaging;neuropathology;nuclear magnetic resonance imaging;occipital lobe;parkinsonism;priority journal;white matter,"Boxer, A. L.;Mackenzie, I. R.;Boeve, B. F.;Baker, M.;Seeley, W. W.;Crook, R.;Feldman, H.;Hsiung, G. Y. R.;Rutherford, N.;Laluz, V.;Whitwell, J.;Foti, D.;McDade, E.;Molano, J.;Karydas, A.;Wojtas, A.;Goldman, J.;Mirsky, J.;Sengdy, P.;DeArmond, S.;Miller, B. L.;Rademakers, R.",2011,,,0,
5261,Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy,"BACKGROUND: Progressive brain atrophy is associated with the corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP). Regional differences in brain atrophy may reflect the clinical features of disease. OBJECTIVE: To quantify the structural neuroanatomical differences between CBDS and PSP. DESIGN: A survey of neurologic deficits was conducted in all patients. Voxel-based morphometry was used to quantify structural neuroanatomical differences on magnetic resonance images in each subject group. SETTING: University hospital dementia clinic. PARTICIPANTS: Fourteen patients who met clinical research criteria for CBD and 15 patients who met clinical research criteria for PSP, who were matched for severity of disease, age, and functional status, and 80 age-matched control subjects. MAIN OUTCOME MEASURES: Statistically significant differences in regional gray and white matter volume, after multiple comparisons correction, between groups of subjects. RESULTS: The patients with CBDS displayed an asymmetric (left > right) pattern of brain atrophy that involved the bilateral premotor cortex, superior parietal lobules, and striatum. Progressive supranuclear palsy was associated with atrophy of the midbrain, pons, thalamus, and striatum, with minimal involvement of the frontal cortex. Midbrain structures were more atrophied in PSP than in CBD, whereas dorsal frontal and parietal cortices were more atrophied in CBD than in PSP. The degree of atrophy of the midbrain and pontine tegmentum and the left frontal eye field differentiated the 2 patient groups with 93% accuracy. CONCLUSIONS: Distinct patterns of brain atrophy exist in CBDS and PSP that can be used to differentiate the 2 diseases. Assessments of brain atrophy in these disorders should be focused on cortical and brainstem ocular motor control areas.","Aged;Atrophy/pathology;Basal Ganglia/ pathology;Brain Mapping;Case-Control Studies;Cerebral Cortex/ pathology;Demography;Female;Functional Laterality;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Degeneration/ pathology/physiopathology;Supranuclear Palsy, Progressive/ pathology/physiopathology","Boxer, A. L.;Geschwind, M. D.;Belfor, N.;Gorno-Tempini, M. L.;Schauer, G. F.;Miller, B. L.;Weiner, M. W.;Rosen, H. J.",2006,Jan,10.1001/archneur.63.1.81,0,
5262,"Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging","OBJECTIVE: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. METHODS: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. RESULTS: Mean age was 87 +/- 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine omega-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine omega-3 pattern and white matter hyperintensity volume. CONCLUSION: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population.","Aged, 80 and over;Aging/ physiology/ psychology;Apolipoprotein E3/genetics;Biomarkers;Brain/ growth & development/ physiology;Cognition/ physiology;Cohort Studies;Demography;Diet;Fatty Acids, Omega-3/blood;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Nutritional Status;Polymerase Chain Reaction;Psychometrics;Regression Analysis;Risk Factors;Vitamins/blood","Bowman, G. L.;Silbert, L. C.;Howieson, D.;Dodge, H. H.;Traber, M. G.;Frei, B.;Kaye, J. A.;Shannon, J.;Quinn, J. F.",2012,Jan 24,10.1212/WNL.0b013e3182436598,0,
5263,Blood-brain barrier impairment in Alzheimer disease: stability and functional significance,"OBJECTIVE: To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD). METHODS: Thirty-six patients (mean age 71 +/- 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 +/- 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI). RESULTS: BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r(2) = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r(2) = 0.29, p = 0.001), and annual ventricular volume change (r(2) = 0.17, p = 0.007). CONCLUSIONS: Blood-brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF-albumin index and measures of disease progression over 1 year.","Age Factors;Aged;Albumins/ cerebrospinal fluid;Alzheimer Disease/ blood/ cerebrospinal fluid/physiopathology;Apolipoproteins E/genetics;Biomarkers/analysis/blood/cerebrospinal fluid;Blood-Brain Barrier/metabolism/ physiopathology;Body Mass Index;Brain/blood supply/pathology/ physiopathology;Cerebrovascular Disorders/complications/diagnosis;Disease Progression;Female;Genetic Predisposition to Disease/genetics;Humans;Hypertension/complications;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Predictive Value of Tests;Risk Factors;Sex Factors","Bowman, G. L.;Kaye, J. A.;Moore, M.;Waichunas, D.;Carlson, N. E.;Quinn, J. F.",2007,May 22,10.1212/01.wnl.0000262031.18018.1a,0,
5264,Plasma omega-3 PUFA and white matter mediated executive decline in older adults,"INTRODUCTION: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association. METHODS: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function. RESULTS: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 mug/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model. CONCLUSION: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.",cognitive decline;hypertension;memory;omega-3 fatty acids;white matter hyperintensity,"Bowman, G. L.;Dodge, H. H.;Mattek, N.;Barbey, A. K.;Silbert, L. C.;Shinto, L.;Howieson, D. B.;Kaye, J. A.;Quinn, J. F.",2013,,10.3389/fnagi.2013.00092,0,
5265,"MRI parameters of Alzheimer's disease in an Arab population of Wadi Ara, Israel","Magnetic resonance imaging (MRI) findings are reported from 15 individuals in an Arab-Israeli community who were diagnosed with Alzheimer's disease (AD). The quantitative parameters that were used for MRI analyses included gradings (0-3) and linear measurements of different brain structures. Generalized tissue loss was assessed by combined measurements of the ventricles (ventricular score, VS) and sulcal grading and width (SG, SW, respectively). Loss of brain tissue in specific regions of interest, eg, temporal lobes, basal ganglia, and midbrain, was evaluated by precise measurements. We observed abnormal tissue characteristics, expressed as high intensity foci in white matter on T2W sequences, as well as tissue loss, both generalized and focal. Most notable were changes involving the head of the caudate nuclei, the midbrain, and to a lesser degree, medial temporal structures.",,"Bowirrat, A.;Reider, G., II;Oscar-Berman, M.;Aizenstein, O.;Levy, G.;Korczyn, A. D.",2005,Mar,,0,
5266,MR signal abnormalities in memory disorder and dementia,"MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p < .0005) and subcortical lesions (r = .39, p < .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p < .01), subcortical lesions (r = .27, p < .0002), and cortical lesions (r = .32, p < .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 ± 4.6, 7.6 ± 4.8, and 3.4 ± 2.6, while mean scores for subcortical lesions were 10.8 ± 12.2, 4.1 ± 6.4, and 0.8 ± 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease. Thus, scores for both periventricular and subcortical lesions are positively correlated with age and risk factors for cerebrovascular disease and also are significantly increased in the presence of objective memory disorder or dementia. These results imply that in the subject groups considered here, elderly patients with vascular dementia are most likely to have severe white-matter abnormalities on MR scans. The score for subcortical lesions appears to be more helpful than the score for periventricular lesions in distinguishing vascular dementia from Alzheimer disease and normal aging, so that a patient with prominent subcortical white-matter abnormalities is more likely to have a diagnosis of vascular than degenerative dementia.",adult;aged;Alzheimer disease;article;brain ischemia;computer analysis;dementia;human;leukoaraiosis;major clinical study;memory;multiinfarct dementia;nuclear magnetic resonance imaging;psychological aspect,"Bowen, B. C.;Barker, W. W.;Loewenstein, D. A.;Sheldon, J.;Duara, R.",1990,,,0,5267
5267,MR signal abnormalities in memory disorder and dementia,"MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p < .0005) and subcortical lesions (r = .39, p < .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p < .01), subcortical lesions (r = .27, p < .0002), and cortical lesions (r = .32, p < .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 ± 4.6, 7.6 ± 4.8, and 3.4 ± 2.6, while mean scores for subcortical lesions were 10.8 ± 12.2, 4.1 ± 6.4, and 0.8 ± 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identifed in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease. Thus, scores for both periventricular and subcortical lesions are positively correlated with age and risk factors for cerebrovascular disease and also are significantly increased in the presence of objective memory disorder or dementia. These results imply that in the subject groups considered here, elderly patients with vascular dementia are most likely to have severe white-matter abnormalities on MR scans. The score for subcortical lesions appears to be more helpful than the score for periventricular lesions in distinguishing vascular dementia from Alzheimer disease and normal aging, so that a patient with prominent subcortical white-matter abnormalities is more likely to have a diagnosis of vascular than degenerative dementia.",,"Bowen, B. C.;Barker, W. W.;Loewenstein, D. A.;Sheldon, J.;Duara, R.",1990,1990,,0,
5268,Abnormalities of Cerebral Deep Medullary Veins on 7 Tesla MRI in Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease: A Pilot Study,"Cerebral small vessel disease (SVD) contributes to cognitive impairment and dementia. SVD may affect veins, but veins are difficult to detect with 1.5 and 3T MRI. We compared deep medullary veins (DMVs) visualized on 7T-MRI between patients with early Alzheimer's disease (eAD; n = 17) or amnestic MCI (aMCI; n = 12) and controls (n = 40). The number and density of DMVs was similar in patients and controls, but tortuosity was higher in eAD (Cohen's d = 0.7, 95% CI: 0.1-1.2, p = 0.02) and aMCI (Cohen's d = 0.8, 95% CI: 0.2-1.5, p = 0.01), independent of brain atrophy. Venous changes provide a new perspective on vascular involvement in dementia.","Aged;Aged, 80 and over;Alzheimer Disease/ congenital/ diagnostic imaging;Analysis of Variance;Brain/diagnostic imaging;Cerebral Small Vessel Diseases/diagnostic imaging/ etiology;Cognitive Dysfunction/ complications/ diagnostic imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Alzheimer's disease;cerebral small vessel disease;cerebral veins","Bouvy, W. H.;Kuijf, H. J.;Zwanenburg, J. J.;Koek, H. L.;Kappelle, L. J.;Luijten, P. R.;Ikram, M. K.;Biessels, G. J.;Utrecht Vascular Cognitive Impairment Study, group",2017,,,0,5269
5269,Abnormalities of Cerebral Deep Medullary Veins on 7 Tesla MRI in Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease: A Pilot Study,"Cerebral small vessel disease (SVD) contributes to cognitive impairment and dementia. SVD may affect veins, but veins are difficult to detect with 1.5 and 3T MRI. We compared deep medullary veins (DMVs) visualized on 7T-MRI between patients with early Alzheimer's sisease (eAD; n = 17) or amnestic MCI (aMCI; n = 12) and controls (n = 40). The number and density of DMVs was similar in patients and controls, but tortuosity was higher in eAD (Cohen's d = 0.7, 95% CI: 0.1-1.2, p = 0.02) and aMCI (Cohen's d = 0.8, 95% CI: 0.2-1.5, p = 0.01), independent of brain atrophy. Venous changes provide a new perspective on vascular involvement in dementia.",Alzheimer's disease;cerebral small vessel disease;cerebral veins;magnetic resonance imaging,"Bouvy, W. H.;Kuijf, H. J.;Zwanenburg, J. J.;Koek, H. L.;Kappelle, L. J.;Luijten, P. R.;Ikram, M. K.;Biessels, G. J.;Utrecht Vascular Cognitive Impairment Study, group",2017,Mar 06,,0,
5270,[Vascular dementia] Les demences vasculaires,"The increasing prevalence of dementia with age, combined with the rapid aging of the population, heralds an oncoming epidemic of dementia in industrialized countries. The current prevalence of dementia over 65 years of age is close to 7% (2/3 Alzheimer's disease and 1/3 vascular dementia). Vascular dementia refers to a severe cognitive decline due to brain lesions of vascular origin. It is in fact a heterogeneous syndrome with multiple etiopathogenic varieties such as subcortical small artery disease, isolated strategic stroke, multiple infarcts, chronic cerebral hypoperfusion, and amyloid angiopathy. Vascular dementia classically occurs or worsens abruptly and has a subcortical pattern of cognitive impairment, contrasting with the gradual cortical dementia of Alzheimer's disease. Recent data, including the results of neuro-imaging studies, show however that this classical opposition is no longer justified and that most dementias are ""mixed"", with a synergy between Alzheimer's disease lesions and vascular risk factors going from, silent brain lesions of vascular origin, to at most, clinically patent strokes. The main therapeutic implication is that, in the absence of effective methods for Alzheimer's disease prevention, the best way to prevent dementia in general is to prevent strokes, based primarily on early treatment of vascular risk factors, particularly hypertension.","0 (Cholinesterase Inhibitors);0 (Excitatory Amino Acid Antagonists);Cholinesterase Inhibitors/therapeutic use;Dementia, Vascular/diagnosis/ etiology/ therapy;Excitatory Amino Acid Antagonists/therapeutic use;Humans","Bousser, M. G.;Chabriat, H.",2012,Feb,,0,
5271,Vascular dementia,"The increasing prevalence of dementia with age, combined with the rapid aging of the population, heralds an oncoming epidemic of dementia in industrialized countries. The current prevalence of dementia over 65 years of age is close to 7% (2/3 Alzheimer's disease and 1/3 vascular dementia). Vascular dementia refers to a severe cognitive decline due to brain lesions of vascular origin. It is in fact a heterogeneous syndrome with multiple etiopathogenic varieties such as subcortical small artery disease, isolated strategic stroke, multiple infarcts, chronic cerebral hypoperfusion, and amyloid angiopathy. Vascular dementia classically occurs or worsens abruptly and has a subcortical pattern of cognitive impairment, contrasting with the gradual cortical dementia of Alzheimer's disease. Recent data, including the results of neuro-imaging studies, show however that this classical opposition is no longer justified and that most dementias are ""mixed"", with a synergy between Alzheimer's disease lesions and vascular risk factors going from, silent brain lesions of vascular origin, to at most, clinically patent strokes. The main therapeutic implication is that, in the absence of effective methods for Alzheimer's disease prevention, the best way to prevent dementia in general is to prevent strokes, based primarily on early treatment of vascular risk factors, particularly hypertension.","Cholinesterase Inhibitors/therapeutic use;Dementia, Vascular/diagnosis/ etiology/ therapy;Excitatory Amino Acid Antagonists/therapeutic use;Humans","Bousser, M. G.;Chabriat, H.",2012,Feb,,0,
5272,"Hyperglycaemia, microangiopathy, diabetes and dementia risk","Brain microangiopathy increases in frequency and severity with older age, with the presence of hypertension and to a lesser extent with diabetes. Magnetic resonance imaging is used to provide anatomical descriptions, but at this time only clinical examination and neuropsychological testing can assess white matter functioning. Clinical correlates of microangiopathy appear as subcortical cognitive alterations, but data are controversial about dementia risk. Brain microangiopathy seems to be however a complication of chronic hyperglycaemia, probably due to similar mechanisms occurring in retinopathy and other microvascular complications. To date, many questions have been raised: How can brain microangiopathy progression be monitored? Is there a reversible stage of brain microangiopathy? Which preventive actions should be implemented in aging patients with diabetes? Finally, what type of care should be provided for people with diabetes and mild cognitive impairment or overt dementia to slow down cognitive worsening? © 2010 Elsevier Masson SAS.",,"Bourdel-Marchasson, I.;Mouries, A.;Helmer, C.",2010,October,,0,
5273,Myelin breakdown in human Huntington's disease: Multi-modal evidence from diffusion MRI and quantitative magnetization transfer,"Huntington's disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. While patients' performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients' performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.",clinical study;corpus callosum;diffusion weighted imaging;executive function;female;fiber;fractional anisotropy;human;Huntington chorea;male;prefrontal cortex;principal component analysis;putamen;radiation;rating scale;supplementary motor area;thalamus;white matter;working memory;myelin;proton,"Bourbon-Teles, J.;Bells, S.;Jones, D. K.;Coulthard, E.;Rosser, A.;Metzler-Baddeley, C.",2017,,10.1016/j.neuroscience.2017.05.042,0,
5274,"Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications","Sporadic cerebral amyloid angiopathy is a small vessel disorder defined pathologically by progressive amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of amyloid peptide (Aβ) in the brain. Cerebral amyloid angiopathy is a major cause of lobar symptomatic intracerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of amyloid-β deposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review.",amyloid beta protein;anticoagulant agent;apolipoprotein E;article;brain hemorrhage;cognitive defect;cortical superficial siderosis;encephalitis;genetic risk;human;neuroimaging;nuclear magnetic resonance imaging;pathophysiology;patient care;prevalence;priority journal;siderosis;vascular amyloidosis,"Boulouis, G.;Charidimou, A.;Greenberg, S. M.",2016,,,0,
5275,Intracranial atherosclerosis and cerebral small vessel disease in intracerebral hemorrhage patients,"BACKGROUND: The association between cerebral small vessel diseases (cSVD) and intracranial atherosclerosis is debated and conflicting results have been reported. We sought to investigate this association in patients with intracerebral hemorrhage (ICH), due to severe cSVD. METHODS: Consecutive ICH patients were divided into those meeting criteria for cerebral amyloid angiopathy (CAA) and those with deep hypertensive ICH consistent with hypertensive cSVD (HTN-SVD). White matter hyperintensity volumes (WMH) and microbleed counts (MB) were measured on MRI. CTA was rated for severity of intracranial carotid calcifications and for presence of >50% intracranial stenosis (ICS). Associations of intracranial atherosclerosis severity with type of SVD (CAA vs HTN-cSVD) and with imaging and clinical markers of cSVD burden were analyzed. RESULTS: The cohort included 253 CAA and 90 HTN-SVD patients. In multivariable models, the type of cSVD (CAA vs. HTN-cSVD) was not associated with calcification severity (OR=1.04, 95% CI [0.62-3.5], p=0.37) or presence of ICS (OR=0.84, 95% CI [0.21-2.74], p=0.78). We found no association between intracranial atherosclerosis (calcifications and stenoses) and parenchymal markers of cSVD severity (WMH and MB, adjusted p>/=0.2 for all comparisons) and no association with presence of dementia before ICH (adjusted p>/=0.2 for both comparisons). CONCLUSIONS: We found no association between intracranial atherosclerosis and parenchymal or clinical consequences of cSVD, suggesting that cSVDs while sharing some risk factors are not influenced by upstream larger vessel pathologies.",Atherosclerosis;CT angiography;Carotid;Intracerebral hemorrhage;Small vessel disease,"Boulouis, G.;Charidimou, A.;Auriel, E.;Haley, K. E.;van Etten, E. S.;Fotiadis, P.;Reijmer, Y.;Ayres, A.;Schwab, K. M.;Martinez-Ramirez, S.;Rosand, J.;Viswanathan, A.;Goldstein, J. N.;Greenberg, S. M.;Gurol, M. E.",2016,Oct 15,10.1016/j.jns.2016.08.049,0,
5276,GOOD or BAD responder? Behavioural and neuroanatomical markers of clinical response to donepezil in dementia,"We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that the BAD-responders had larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.","Aged;Aged, 80 and over;Alzheimer Disease/*drug therapy/pathology/psychology;Atrophy;Biomarkers/*analysis;Brain/pathology;Cholinesterase Inhibitors/*therapeutic use;Female;Humans;Indans/*therapeutic use;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Piperidines/*therapeutic use;Treatment Outcome","Bottini, G.;Berlingeri, M.;Basilico, S.;Passoni, S.;Danelli, L.;Colombo, N.;Sberna, M.;Franceschi, M.;Sterzi, R.;Paulesu, E.",2012,,,0,
5277,Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech,"The consensus criteria for the diagnosis and classification of primary progressive aphasia (PPA) have served as an important tool in studying this group of disorders. However, a large proportion of patients remain unclassifiable whilst others simultaneously meet criteria for multiple subtypes. We prospectively evaluated a large cohort of patients with degenerative aphasia and/or apraxia of speech using multidisciplinary clinical assessments and multimodal imaging. Blinded diagnoses were made using operational definitions with important differences compared to the consensus criteria. Of the 130 included patients, 40 were diagnosed with progressive apraxia of speech (PAOS), 12 with progressive agrammatic aphasia, 9 with semantic dementia, 52 with logopenic progressive aphasia, and 4 with progressive fluent aphasia, while 13 were unclassified. The PAOS and progressive fluent aphasia groups were least impaired. Performance on repetition and sentence comprehension was especially poor in the logopenic group. The semantic and progressive fluent aphasia groups had prominent anomia, but only semantic subjects had loss of word meaning and object knowledge. Distinct patterns of grey matter loss and white matter changes were found in all groups compared to controls. PAOS subjects had bilateral frontal grey matter loss, including the premotor and supplementary motor areas, and bilateral frontal white matter involvement. The agrammatic group had more widespread, predominantly left sided grey matter loss and white matter abnormalities. Semantic subjects had bitemporal grey matter loss and white matter changes, including the uncinate and inferior occipitofrontal fasciculi, whereas progressive fluent subjects only had left sided temporal involvement. Logopenic subjects had diffuse and bilateral grey matter loss and diffusion tensor abnormalities, maximal in the posterior temporal region. A diagnosis of logopenic aphasia was strongly associated with being amyloid positive (46/52 positive). Our findings support consideration of an alternative way of identifying and categorizing subtypes of degenerative speech and language disorders.",,"Botha, H.;Duffy, J. R.;Whitwell, J. L.;Strand, E. A.;Machulda, M. M.;Schwarz, C. G.;Reid, R. I.;Spychalla, A. J.;Senjem, M. L.;Jones, D. T.;Lowe, V.;Jack, C. R.;Josephs, K. A.",2015,Aug,10.1016/j.cortex.2015.05.013,0,
5278,"Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance","White matter (WM) damage has been reported in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) in diffusion tensor imaging (DTI) studies. It is, however, unknown how the investigation of multiple tensor indexes in the same patients, can differentiate them from normal aging or relate to patients cognition. Forty-six individuals (15 healthy, 16 a-MCI and 15 AD) were included. Voxel-based tract based spatial-statistics (TBSS) was used to obtain whole-brain maps of main WM bundles for fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA) and mean diffusivity (MD).",,"Bosch, B.;Arenaza-Urquijo, E. M.;Rami, L.;Sala-Llonch, R.;Junqué, C.;Solé-Padullés, C.;Peña-Gómez, C.;Bargalló, N.;Molinuevo, J. L.;Bartrés-Faz, D.",2012,January,,0,
5279,Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline,"BACKGROUND: Cerebrovascular disease (CVD) and amyloid-beta (Abeta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Abeta on neurodegenerative markers and cognition in patients without dementia. METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Abeta1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Abeta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Abeta and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. RESULTS: MTA and t-tau were elevated in the Abeta - WMH+, Abeta + WMH-, and Abeta + WMH+ groups. MTA was most severe in the Abeta + WMH+ group compared with the groups with a single pathology. Both WMH and Abeta were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. CONCLUSIONS: In the present study, we found an additive association of Abeta and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.",Alzheimer's disease;Amyloid;Cerebrospinal fluid;Cerebrovascular disease;Cognition;Mri;Medial temporal lobe atrophy;Neurodegeneration;Tau,"Bos, I.;Verhey, F. R.;Ramakers, Ihgb;Jacobs, H. I. L.;Soininen, H.;Freund-Levi, Y.;Hampel, H.;Tsolaki, M.;Wallin, A. K.;van Buchem, M. A.;Oleksik, A.;Verbeek, M. M.;Olde Rikkert, M.;van der Flier, W. M.;Scheltens, P.;Aalten, P.;Visser, P. J.;Vos, S. J. B.",2017,Dec 29,,0,
5280,Atherosclerotic calcification relates to cognitive function and to brain changes on magnetic resonance imaging,"BACKGROUND: Increasing evidence suggests a role of atherosclerosis in the pathogenesis of cognitive impairment and dementia. Calcification volume measured with computed tomography (CT) is a valid marker of atherosclerosis. This study investigates associations of atherosclerosis (measured using CT) at four locations with cognition and brain changes on magnetic resonance imaging (MRI). METHODS: To quantify calcification volume, 2414 nondemented people from the Rotterdam Study underwent CT of the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. To assess global cognition and performance on memory, executive function, information processing speed, and motor speed, they also underwent neuropsychological tests. In a random subgroup of 844 participants, brain MRI was performed. Automated segmentation and quantification of brain MRI scans yielded brain tissue volumes in milliliters. Diffusion tensor imaging was used to measure the microstructural integrity of the white matter. Relationships of atherosclerotic calcification with cognition, brain tissue volumes, and diffusion tensor imaging measures were assessed with linear regression models and adjusted for relevant confounders. RESULTS: With larger calcification volumes, lower cognitive scores were observed. When calcification volumes were larger, total brain volumes were also smaller. Specifically, larger coronary artery calcification volumes related to smaller gray matter volumes, and extracranial and intracranial carotid calcification volumes related to smaller white matter volumes. Larger calcification volume in all vessel beds was accompanied by worse microstructural integrity of the white matter. CONCLUSIONS: Larger calcification volume is associated with worse cognitive performance. It also relates to smaller brain tissue volumes and worse white matter microstructural integrity, revealing possible mechanisms through which atherosclerosis may lead to poorer cognition.","Aged;Aorta, Thoracic/pathology/radiography;Atherosclerosis/ complications/pathology/radiography;Brain/blood supply/ pathology/radiography;Calcinosis/ complications/pathology/radiography;Carotid Arteries/pathology/radiography;Cognition Disorders/ etiology/ pathology/radiography;Coronary Vessels/pathology/radiography;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Tomography, X-Ray Computed","Bos, D.;Vernooij, M. W.;Elias-Smale, S. E.;Verhaaren, B. F.;Vrooman, H. A.;Hofman, A.;Niessen, W. J.;Witteman, J. C.;van der Lugt, A.;Ikram, M. A.",2012,Oct,10.1016/j.jalz.2012.01.008,0,
5281,White matter changes in corticobasal degeneration syndrome and correlation with limb apraxia,"BACKGROUND: Data on white matter changes in corticobasal degeneration syndrome (CBDS) are not yet available, whereas cortical gray matter loss is a feature of this condition. The structural abnormalities related to a key feature of CBDS (limb apraxia) are unknown. OBJECTIVES: To measure selective structural changes in early CBDS using diffusion tensor imaging and voxel-based morphometry and to evaluate the structural correlates of limb apraxia. DESIGN: Patient and control group comparison. SETTING: Referral center for dementia and movement disorders. PARTICIPANTS: Twenty patients with CBDS and 21 matched control subjects. INTERVENTIONS: Clinical and standardized neuropsychological evaluations, including assessment of limb apraxia. MAIN OUTCOME MEASURES: Gray and white matter changes in early CBDS. RESULTS: Diffusion tensor imaging revealed decreases in fractional anisotropy in the long frontoparietal connecting tracts, the intraparietal associative fibers, and the corpus callosum. Fractional anisotropy was also reduced in the sensorimotor projections of the cortical hand areas. Voxel-based morphometry showed a prevalent gray matter reduction in the left hemisphere (in the inferior frontal and premotor cortices, parietal operculum, superotemporal gyrus, and hippocampus). The pulvinar, bilaterally, and the right cerebellar cortex also showed atrophy. Limb apraxia correlated with parietal atrophy and with fractional anisotropy reductions in the parietofrontal associative fibers (P < .01). The limb-kinetic component of apraxia correlated with reduction of hand sensorimotor connecting fibers. CONCLUSIONS: The present integrative approach to in vivo structural anatomy combines hodologic imaging, describing patterns of white matter connections between cortical areas, with neuropsychological data. This provides new evidence of gray matter and fiber tract abnormalities in early-phase disease and contributes to clarifying the neural basis of apraxia in CBDS.",Aged;Apraxias/diagnosis/ pathology/psychology;Basal Ganglia Diseases/diagnosis/ pathology/psychology;Cerebral Cortex/ pathology;Corpus Callosum/ pathology;Diffusion Magnetic Resonance Imaging/methods;Extremities/pathology;Female;Humans;Male;Middle Aged;Neurodegenerative Diseases/diagnosis/ pathology/psychology;Syndrome,"Borroni, B.;Garibotto, V.;Agosti, C.;Brambati, S. M.;Bellelli, G.;Gasparotti, R.;Padovani, A.;Perani, D.",2008,Jun,10.1001/archneur.65.6.796,0,
5282,Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38),"INTRODUCTION: SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified. OBJECTIVE: The present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38. METHODS: We extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian families. All had the ELOVL5 c.689G > T (p.Gly230Val) missense mutation. RESULTS: Age at disease onset was in the fourth decade of life. The presenting features were nystagmus (100% of cases) and slowly progressive gait ataxia (95%). Frequent signs and symptoms included pes cavus (82%) and hyposmia (76%); rarer symptoms were hearing loss (33%) and anxiety disorder (33%). The disease progressed with cerebellar symptoms such as limb ataxia, dysarthria, dysphagia, and ophtalmoparesis followed in the later stages by ophtalmoplegia. Peripheral nervous system involvement was present in the last phase of disease with sensory loss. Dementia or extrapyramidal signs were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented cerebellar atrophy with sparing of cerebral cortex and no white matter disease. CONCLUSIONS: SCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions.",Ataxia;Elovl5;Gene;Mutation;Sca38,"Borroni, B.;Di Gregorio, E.;Orsi, L.;Vaula, G.;Costanzi, C.;Tempia, F.;Mitro, N.;Caruso, D.;Manes, M.;Pinessi, L.;Padovani, A.;Brusco, A.;Boccone, L.",2016,Jul,10.1016/j.parkreldis.2016.04.030,0,
5283,Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia,"BACKGROUND: Two major clinical variants of frontotemporal dementia (FTD) have been described: frontal variant (fvFTD) and temporal variant (tvFTD). OBJECTIVE: To analyze white matter (WM) and gray matter (GM) tissue organization in patients with fvFTD and tvFTD by means of diffusion tensor imaging and voxel-based morphometry, and the correlations with neuropsychological and behavioral variables. DESIGN AND SETTING: Frontotemporal dementia clinic-based cohort and structural magnetic resonance imaging acquisition for voxel-based morphometry and diffusion tensor imaging measurements. Abnormalities were detected by a comparison with healthy control subjects. These variables were also correlated with clinical scores. Patients Thirty-six patients (28 with fvFTD and 8 with tvFTD) in early disease stage and 23 healthy controls who underwent standardized clinical and neuropsychological evaluation and magnetic resonance imaging. INTERVENTIONS: Diffusion tensor imaging and voxel-based morphometry. MAIN OUTCOME MEASURES: Neuroimaging analyses resulted in localized GM atrophy and reductions of white matter densities; the latter correlated with behavioral scores. RESULTS: Voxel-based morphometry analysis showed separate patterns of GM atrophy in the 2 groups. Diffusion tensor imaging showed different WM reduction patterns in patients with fvFTD and tvFTD. The fvFTD group showed a selective WM reduction in the superior longitudinal fasciculus, interconnecting the frontal and occipital and the temporal and parietal regions. Conversely, patients with tvFTD were characterized by WM reductions in the inferior longitudinal fasciculus, which affected the connections between anterior temporal and frontal regions. The WM reductions in fvFTD paralleled both behavioral disturbances measured by Frontal Behavioral Inventory and neuropsychological deficits affecting frontal functions. CONCLUSIONS: The fvFTD and tvFTD variants are associated not only with selective local GM reductions but also with significant WM damage in early disease phase. The different WM patterns contribute to the different clinical syndromes in FTD and could be responsible for the further progression of atrophy in the later disease stages.",Aged;Atrophy/pathology;Brain Mapping;Dementia/ pathology/ physiopathology;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Neuropsychological Tests,"Borroni, B.;Brambati, S. M.;Agosti, C.;Gipponi, S.;Bellelli, G.;Gasparotti, R.;Garibotto, V.;Di Luca, M.;Scifo, P.;Perani, D.;Padovani, A.",2007,Feb,10.1001/archneur.64.2.246,0,
5284,Magnetic resonance imaging of white matter lesions in HIV infection,"Previous studies of the frequency of high-signal lesions in human immunodeficiency virus (HIV) infection have had methodological weaknesses regarding lack of control groups, differing machine strengths, and biased subject selection. To obtain a more accurate estimate of prevalence, MRI scans were performed on 243 HIV-positive and HIV-negative homosexual or bisexual men with no history of intravenous drug use. Axial T2-weighted (long TR/TE, spin-echo) MRI scans were rated blindly for presence of focal white matter high-signal lesions. Incidence of hyperintensities was low in all groups, although slightly higher in patients with AIDS, and was not associated with neuropsychological performance. The lower incidence of hyperintensities appears to relate to elimination of methodological problems in previous studies.",AIDS Dementia Complex/ diagnosis/psychology;Adult;Bisexuality/psychology;Brain/ pathology;Homosexuality/psychology;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests,"Bornstein, R. A.;Chakeres, D.;Brogan, M.;Nasrallah, H. A.;Fass, R. J.;Para, M.;Whitacre, C.",1992,Spring,10.1176/jnp.4.2.174,0,
5285,Do silent brain infarctions predict the development of dementia after first ischemic stroke?,"BACKGROUND AND PURPOSE: Silent brain infarctions (SBI) are common findings in advanced age, but their relationship to dementia is still uncertain. The present study was designed to evaluate whether SBI predict the development of dementia after first clinical ischemic stroke. METHODS: We blindly studied admission CT scans of 175 consecutive nondemented patients presenting with ischemic stroke that clinically was their first stroke episode. SBI were defined as CT evidence of infarcts not compatible with the acute event. The patients were subsequently followed for their mental state for 5 years. Survival analysis, wherein onset of dementia was the end point, was performed on the total sample population and conducted separately on those with and without SBI at admission. RESULTS: Dementia developed in 56 patients (32%), including 22 of the 63 (35%) with SBI and 34 of the 112 (30%) without SBI. Thus, dementia was not related to SBI. CONCLUSIONS: Our data indicate that SBI do not predict the development of dementia after stroke.","Aged;Cerebral Hemorrhage/mortality/*physiopathology/psychology;Cerebral Infarction/mortality/*physiopathology/psychology;Dementia, Multi-Infarct/*epidemiology;Female;Follow-Up Studies;Humans;Ischemic Attack, Transient/mortality/*physiopathology/psychology;Male;Prevalence;Prognosis;Recurrence;Regression Analysis;Retrospective Studies;Risk Factors;Sex Characteristics;Survival Analysis","Bornstein, N. M.;Gur, A. Y.;Treves, T. A.;Reider-Groswasser, I.;Aronovich, B. D.;Klimovitzky, S. S.;Varssano, D.;Korczyn, A. D.",1996,May,,0,
5286,Hereditary cerebral hemorrhage with amyloidosis - Dutch type: Better correlation of cognitive deterioration with advancing age than with number of focal lesions or white matter hyperintensities,"The relationship between cognitive deterioration and abnormalities detected by magnetic resonance imaging (MRI) was investigated to determine the radiological correlates of cognitive deterioration in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). Twenty HCHWA-D subjects (12 patients who had suffered one or more strokes and eight who had not suffered a stroke) were studied with MRI and underwent extensive neuropsychological examination. On MRI the number of focal lesions was counted, and white matter hyperintensities (WMHs) were scored semiquantitatively. A significant correlation between cognitive deterioration and WMH score and number of focal lesions was found. However, cognitive deterioration, WMH score, and the number of focal lesions all increase with age, and therefore their mutual correlation can be explained as an age effect. This study shows that cognitive deterioration in HCHWA-D is not correlated with abnormalities detected by MRI (number of focal lesions and subcortical WMHs) independently of age. Although a contribution of white matter changes and/or focal lesions, possibly in combination with age, to cognitive deterioration cannot be excluded. Cognitive deterioration in these HCHWA-D patients is probably primarily the result of chronic damage of amyloid angiopathy to the brain, to which may be superimposed cognitive impairment from focal cerebral hemorrhage or infarction.",,"Bornebroek, M.;Van Buchem, M. A.;Haan, J.;Brand, R.;Lanser, J. B. K.;De Bruïner, F. T.;Roos, A. C.",1996,1996,,0,
5287,Dutch hereditary cerebral amyloid angiopathy: structural lesions and apolipoprotein E genotype,"Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by a mutation at codon 693 of the beta amyloid precursor protein gene. The disease is clinically characterized by strokes and dementia. In addition to cerebral plaques, cerebral amyloid angiopathy is the pathological hallmark. We investigated the correlation between radiological (white matter hyperintensities and focal lesions on magnetic resonance images) and pathological lesions (cerebrovascular amyloid angiopathy and plaques) and the apolipoprotein E genotype in patients with the disease. Twenty-five patients were studied using magnetic resonance imaging, and brain tissue from 8 patients was studied histopathologically. Neither the white matter hyperintensity scores nor the number of focal lesions on magnetic resonance images were associated with the presence of an epsilon4 allele. Nor was a correlation found between the number and type of plaques and the apolipoprotein E genotype. All patients had severe amyloid angiopathy in all cortical areas investigated. This study showed that the apolipoprotein E genotype does not modulate amyloid-related structural lesions in hereditary cerebral hemorrhage with amyloidosis of the Dutch type.","Adult;Aged;Aged, 80 and over;Apolipoproteins E/ genetics;Brain/pathology;Cerebral Amyloid Angiopathy/ethnology/ genetics/ pathology;Cerebral Cortex/pathology;Female;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Multivariate Analysis;Mutation;Netherlands/epidemiology","Bornebroek, M.;Haan, J.;Van Duinen, S. G.;Maat-Schieman, M. L.;Van Buchem, M. A.;Bakker, E.;Van Broeckhoven, C.;Roos, R. A.",1997,May,10.1002/ana.410410523,0,
5288,White matter lesions and cognitive deterioration in presymptomatic carriers of the amyloid precursor protein gene codon 693 mutation,"Objective: To determine early manifestations of hereditary cerebral hemorrhage with amyloidosis (Dutch). Design: Survey. Setting: Neurologic outpatient department of the University Hospital Leiden in the Netherlands. Participants: Ten presymptomatic carriers of the amyloid precursor protein gene codon 693 mutation. Main Outcome Measurements: Extensive neuropsychological examination and cerebral magnetic resonance imaging. Results: Six subjects older than 40 years showed white matter hyperintensities on magnetic resonance imaging. Three of these six individuals had signs of cognitive deterioration. The four younger subjects (age, <31 years) showed no abnormalities on magnetic resonance imaging or on neuropsychological examination. Conclusions: We suggest that white matter hyperintensities in hereditary cerebral hemorrhage with amyloidosis (Dutch) are probably caused by chronic ischemia due to stenosis of the meningocortical arterioles, which becomes visible on magnetic resonance imaging scans in individuals who are between the ages of 30 and 40 years. The finding of cognitive deterioration in three of 10 presymptomatic mutation carriers supports the finding that in hereditary cerebral hemorrhage with amyloidosis (Dutch), deterioration can occur without stroke. A direct relation between cognitive deterioration and white matter hyperintensities is unlikely, because only half of the individuals with white matter hyperintensities showed signs of deterioration.",,"Bornebroek, M.;Haan, J.;Van Buchem, M. A.;Lanser, J. B. K.;Simone De Vries-vd Weerd, M. A. C.;Zoeteweij, M.;Roos, R. A. C.",1996,January,,0,
5289,"Presenilin-1 polymorphism and hereditary cerebral hemorrhage with amyloidosis, Dutch type","Hereditary cerebral hemorrhage with amyloidosis, Dutch type, caused by a mutation at codon 693 of the amyloid beta precursor protein gene, is characterized by amyloid beta deposition resulting in recurrent strokes and dementia. Recent data suggest that presenilin-1 may be biologically linked to cerebral amyloid beta deposition. The intronic presenilin-1 polymorphism published by Wragg and colleagues (1996) was analyzed in 65 carriers of the hereditary cerebral hemorrhage with amyloidosis, Dutch type, mutation. We found that the presenilin-1 genotype was not correlated with age at first stroke, number of recurrences, dementia, and age at death or with white matter hyperintensities and focal lesions on magnetic resonance images. From our data we conclude that amyloid beta deposition in this disease is most likely not influenced by presenilin-1.","Adult;Aged;Aged, 80 and over;Alleles;Amyloidosis/diagnosis/ genetics;Cerebral Hemorrhage/diagnosis/ genetics;Female;Genotype;Heterozygote;Humans;Magnetic Resonance Imaging;Male;Membrane Proteins/ genetics;Middle Aged;Mutation;Polymorphism, Genetic;Presenilin-1","Bornebroek, M.;Haan, J.;Backhovens, H.;Deutz, P.;Van Buchem, M. A.;van den Broeck, M.;Bakker, E.;Roos, R. A.;Van Broeckhoven, C.",1997,Jul,10.1002/ana.410420116,0,
5290,"Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer's disease","Cardiorespiratory fitness (CRF) is an objective measure of habitual physical activity (PA), and has been linked to increased brain structure and cognition. The gold standard method for measuring CRF is graded exercise testing (GXT), but GXT is not feasible in many settings. The objective of this study was to examine whether a non-exercise estimate of CRF is related to gray matter (GM) volumes, white matter hyperintensities (WMH), cognition, objective and subjective memory function, and mood in a middle-aged cohort at risk for Alzheimer's disease (AD). Three hundred and fifteen cognitively healthy adults (mean age =58.58 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent structural MRI scanning, cognitive testing, anthropometric assessment, venipuncture for laboratory tests, and completed a self-reported PA questionnaire. A subset (n = 85) underwent maximal GXT. CRF was estimated using a previously validated equation incorporating sex, age, body-mass index, resting heart rate, and self-reported PA. Results indicated that the CRF estimate was significantly associated with GXT-derived peak oxygen consumption, validating its use as a non-exercise CRF measure in our sample. Support for this finding was seen in significant associations between the CRF estimate and several cardiovascular risk factors. Higher CRF was associated with greater GM volumes in several AD-relevant brain regions including the hippocampus, amygdala, precuneus, supramarginal gyrus, and rostral middle frontal gyrus. Increased CRF was also associated with lower WMH and better cognitive performance in Verbal Learning & Memory, Speed & Flexibility, and Visuospatial Ability. Lastly, CRF was negatively correlated with self- and informant-reported memory complaints, and depressive symptoms. Together, these findings suggest that habitual participation in physical activity may provide protection for brain structure and cognitive function, thereby decreasing future risk for AD.",Cardiorespiratory fitness;Cognition;Mri;Mood;Preclinical Alzheimer's disease;White matter hyperintensities,"Boots, E. A.;Schultz, S. A.;Oh, J. M.;Larson, J.;Edwards, D.;Cook, D.;Koscik, R. L.;Dowling, M. N.;Gallagher, C. L.;Carlsson, C. M.;Rowley, H. A.;Bendlin, B. B.;LaRue, A.;Asthana, S.;Hermann, B. P.;Sager, M. A.;Johnson, S. C.;Okonkwo, O. C.",2015,Sep,10.1007/s11682-014-9325-9,0,
5291,Dutch Normal-Pressure Hydrocephalus Study: the role of cerebrovascular disease,"OBJECT: This study was conducted to determine the prevalence of cerebrovascular disease and its risk factors among patients with normal-pressure hydrocephalus (NPH) and to assess the influence of these factors on the outcome of shunt placement. METHODS: A cohort of 101 patients with NPH underwent shunt placement and was followed for 1 year. Gait disturbance and dementia were quantified using an NPH scale and handicap was determined using a modified Rankin scale (mRS). Primary outcome measures consisted of the differences between preoperative and last NPH scale and mRS scores. The presence of risk factors such as hypertension, diabetes mellitus, cardiac disease, peripheral vascular disease, male gender, and advancing age was recorded. Cerebrovascular disease was defined as a history of stroke or a computerized tomography (CT) scan revealing infarcts or moderate-to-severe white matter hypodense lesions. The prevalence of risk factors for cerebrovascular disease was higher in the 45 patients with cerebrovascular disease than the 56 without it. Risk factors did not influence outcome after shunt placement. Intent-to-treat analysis revealed that the mean improvement in the various scales was significantly less for patients with a history of stroke (14 patients), CT scans revealing infarctions (13), or white matter hypodense lesions (32 patients) than for those without cerebrovascular disease. The proportion of patients who responded to shunt placement was also significantly lower among patients with than those without cerebrovascular disease (p=0.02). CONCLUSIONS: The authors identified a subgroup of patients with NPH and cerebrovascular disease who showed disappointing results after shunt placement. Cerebrovascular disease was an important predictor of poor outcome.","Aged;Cerebrovascular Disorders/*complications/*epidemiology/etiology;Cohort Studies;Female;Humans;Hydrocephalus, Normal Pressure/*complications/surgery;Male;Prevalence;Risk Factors;Treatment Outcome;Ventriculoperitoneal Shunt","Boon, A. J.;Tans, J. T.;Delwel, E. J.;Egeler-Peerdeman, S. M.;Hanlo, P. W.;Wurzer, H. A.;Hermans, J.",1999,Feb,10.3171/jns.1999.90.2.0221,0,
5292,Imaging and spectroscopic approaches to probe brain energy metabolism dysregulation in neurodegenerative diseases,"Changes in energy metabolism are generally considered to play an important role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Whether these changes are causal or simply a part of self-defense mechanisms is a matter of debate. Furthermore, energy defects have often been discussed solely in the context of their probable neuronal origin without considering the cellular heterogeneity of the brain. Recent data point towards the existence of a tri-cellular compartmentation of brain energy metabolism between neurons, astrocytes, and oligodendrocytes, each cell type having a distinctive metabolic profile. Still, the number of methods to follow energy metabolism in patients is extremely limited and existing clinical techniques are blind to most cellular processes. There is a need to better understand how brain energy metabolism is regulated in health and disease through experiments conducted at different scales in animal models to implement new methods in the clinical setting. The purpose of this review is to offer a brief overview of the broad spectrum of methodological approaches that have emerged in recent years to probe energy metabolism in more detail. We conclude that multi-modal neuroimaging is needed to follow non-cell autonomous energy metabolism dysregulation in neurodegenerative diseases.",Brain imaging;MR spectroscopy;astrocytes;neurodegeneration;white matter/oligodendrocytes,"Bonvento, G.;Valette, J.;Flament, J.;Mochel, F.;Brouillet, E.",2017,Jan 01,,0,
5293,Cognitive disorders in HIV-infected patients: are they HIV-related?,"OBJECTIVES: Large unselected studies on representative samples of HIV-infected patients with a whole battery of neuropsychological tests and cerebral MRI scan are required to assess the frequency of neurocognitive impairment (NCI), the determinants of mild neurocognitive disorders (MNDs), or HIV-associated dementia (HAD) and the relationship between NCI and MRI scan findings. METHODS: Investigation of 400 consecutively enrolled HIV-1-infected adults from the ANRS CO3 Aquitaine Cohort, using standardized neurocognitive tests chosen to achieve consistency with Frascati's criteria. Half of the patients had a cerebral MRI scan allowing gray and white matter volume measurement. Factors associated with NCI were studied by logistic regression models. RESULTS: Median age of participants was 47 years, 79% were male and 89% received combination antiretroviral treatment (cART), of whom 93% had plasma HIV RNA below 500 copies/ml. Median CD4 cell count was 515 cells/mul. Prevalence of NCI was 59%, including 21% of asymptomatic NCI, 31% of MND, and 7% of HAD. A low level of education, prior neurologic AIDS-defining disorders event, anxiety, depressive symptoms, and prior history of brain damage were independently associated with MND or HAD, but neither HIV nor cART-related variables. The presence of NCI was significantly associated with lower gray matter fraction. INTERPRETATION: In this large unselected cohort, a high prevalence of symptomatic neurocognitive disorders was mainly related to its traditional determinants and associated with gray matter atrophy at early stages of the disease.","AIDS Dementia Complex/epidemiology/*pathology;Antiretroviral Therapy, Highly Active;Atrophy;Body Mass Index;Brain/*pathology/virology;CD4 Lymphocyte Count;Cognition Disorders/epidemiology/*pathology/virology;Female;Follow-Up Studies;France/epidemiology;HIV Infections/epidemiology/*pathology;Humans;Logistic Models;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neuropsychological Tests;Prevalence;RNA, Viral/blood/isolation & purification;Surveys and Questionnaires","Bonnet, F.;Amieva, H.;Marquant, F.;Bernard, C.;Bruyand, M.;Dauchy, F. A.;Mercie, P.;Greib, C.;Richert, L.;Neau, D.;Catheline, G.;Dehail, P.;Dabis, F.;Morlat, P.;Dartigues, J. F.;Chene, G.",2013,Jan 28,10.1097/QAD.0b013e32835b1019,0,
5294,Neurological disorders and atrial myxoma. 3 Cases,"We report 2 cases (no 1 and 2) of cerebral infarction caused by a left atrial myxoma, and 1 case (no 3) of dementia associated with a large left atrial myxoma. Cerebral emboli and neurological symptoms which can occur prior to cardiac obstructive and/or systemic signs require echocardiocardiography. The cardiac post-operative condition was dramatically improved in cases revealed by an hemiplegia.",adult;aged;article;brain infarction;dementia;echocardiography;female;heart atrium myxoma;hemiplegia;human;male;nuclear magnetic resonance imaging;priority journal,"Bonnefoi, B.;Mesana, T.;Camilleri, J. F.;Habib, G.;Azulay, J. P.;Khalil, R.",1990,,,0,
5295,Temporal lobe networks supporting the comprehension of spoken words,"Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysio-logical studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based - and structural connectome - lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cin-gulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions.",adult;anomic aphasia;article;ataxic aphasia;brain damage;brain injury;cerebrovascular accident;cingulate gyrus;comprehension;conduction aphasia;connectome;controlled study;cortical sensory aphasia;diffusion tensor imaging;female;fusiform gyrus;human;image analysis;inferior temporal gyrus;language test;major clinical study;male;middle temporal gyrus;neuroimaging;neuropsychological test;nuclear magnetic resonance imaging;oral communication;primary progressive aphasia;priority journal;stroke patient;temporal lobe;voxel based morphometry;white matter lesion,"Bonilha, L.;Hillis, A. E.;Hickok, G.;Den Ouden, D. B.;Rorden, C.;Fridriksson, J.",2017,,10.1093/brain/awx169,0,
5296,The effect of treatment on grey and white matter in Alzheimer's disease patients,"Introduction: despite the numerous quantity of studies into structural MRI changes in Alzheimer's disease, there has been relatively little information related to multimodal structural imaging modifications following treatment (Likitjaroen et al., 2012; Goveas et al., 2011). We examined longitudinal changes in both cerebral volume and microstructure abnormalities in patients with Alzheimer's Disease (AD) before and after treatment with cholinesterase inhibitor Donepezil. Voxel-based morphometry (VBM) was used to measure greymatter volume while diffusion tensor imaging (DTI) was used to measure microstructural white-matter integrity. Longitudinal results were interpreted according to changes observed cross-sectionally between controls, patients with Mild Cognitive Impairment (MCI) and patients with AD. Methods: 70 participants (27 with probable AD, 20 MCI, 23 controls), each accompanied by a study partner, were recruited for the cross-sectional study and underwent multimodal MRI including T1-weighted and diffusion sequences. A subgroup of 18 AD patients, for whom there was clinical indication to commence treatment with Donepezil, were also included in the longitudinal study. They repeated the scan 12 weeks after starting the treatment (5 mg for the first 4 weeks, then 10 mg). All participants undertook neurological examinations and extended neuropsychological assessments prior to the MRI scan. Results: significant effect of treatment was found on both grey-matter volume and white-matter integrity of the cholinergic system. More precisely, treatment increased volume of fronto-insular and basal ganglia regions. Conclusions: this study suggests that cholinesterase inhibitors may potentiate compensatory structural and microstructural changes in patients with AD. Further placebocontrolled longer studies should be undertaken to confirm our results and to test if the treatment effects on structural MRI persist over a longer term.",human;white matter;patient;nuclear magnetic resonance imaging;diffusion tensor imaging;basal ganglion;gray matter;neurologic examination;voxel based morphometry;longitudinal study;diffusion;cross-sectional study;cholinergic system;mild cognitive impairment;imaging;cholinesterase inhibitor;donepezil;n [2 (2 methoxyphenyl)acetyl]dehydroalanine,"Bonifacio, G. B.;Tondelli, M.;Wilcock, G.;Nichelli, P.;Zamboni, G.",2013,,,0,
5297,Magnetic resonance imaging and the severity of dementia in older adults,"Periventricular white-matter lesions were visualized in the brains of elderly patients being assessed for possible Alzheimer's disease. The magnitude of these lesions, expressed as lesion-brain ratios, correlated closely with the severity of dementia indicated by scores on the Blessed Dementia Scale and the Folstein Mini-Mental State Examination. Impairment in several domains of cognitive functioning tested by the Mini-Mental State Examination was also correlated with the relative quantity of periventricular lesions. Correlations were significant with systolic blood pressure, approached significance with age, and were not significant with duration of dementia or the magnitude of the lateral ventricles. These findings indicate the potential utility of structure-function correlations that are possible with magnetic resonance imaging in identifying mechanisms underlying dementia. They suggest that magnetic resonance imaging may be more useful than computed tomography in following the course of dementia.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/pathology;Anthropometry;Brain/anatomy & histology/ pathology;Cerebral Ventricles/anatomy & histology;Female;Humans;Magnetic Resonance Imaging;Male;Psychiatric Status Rating Scales;Psychological Tests;Severity of Illness Index;Tomography, X-Ray Computed","Bondareff, W.;Raval, J.;Woo, B.;Hauser, D. L.;Colletti, P. M.",1990,Jan,,0,
5298,Quantitative magnetic resonance imaging and the severity of dementia in Alzheimer's disease,"The T2 component of the magnetic resonance imaging (MRI) signal was measured in 11 brain loci in six elderly patients diagnosed as having probable Alzheimer's disease. T2 values and relative amount of periventricular high-intensity foci were significantly correlated with dementia severity, indicated by the Blessed-Roth Dementia Scale score. Although the mean T2 value for left hemispheric structures was more closely correlated with the dementia score, T2 values did not differ significantly in the right and left hemispheres or in gray and white matter. These findings suggest that more severe dementia in Alzheimer's disease is associated with more water in the brain.",Aged;Alzheimer Disease/ diagnosis/pathology/psychology;Body Water/analysis;Brain/ pathology;Brain Chemistry;Functional Laterality;Humans;Magnetic Resonance Imaging;Psychiatric Status Rating Scales,"Bondareff, W.;Raval, J.;Colletti, P. M.;Hauser, D. L.",1988,Jul,10.1176/ajp.145.7.853,0,
5299,A new rapid landmark-based regional MRI segmentation method of the brain,"BACKGROUND: Neurodegenerative and cerebrovascular diseases show a distinct distribution of regional atrophy and subcortical lesions. OBJECTIVE: To develop an easily applicable landmark-based method for segmentation of the brain into the four cerebral lobes from MRI images. METHOD: The segmentation method relies on a combination of anatomical landmarks and geometrical definitions. It is applied on the surface reconstruction of the MRI volume. The internal borders between the lobes are defined on the axial slices of the brain. The reliability of this method was determined from MRI scans of 10 subjects. To illustrate the use of the method, it was applied to MRI scans of an independent group of 10 healthy elderly subjects and 10 patients with vascular dementia to determine the regional distribution of white matter hyperintensities (WMH). RESULTS: The intra-rater relative error (and intra-class correlation coefficient) of the lobe segmentation ranged from 1.6% to 6.9% (from 0.91 to 0.99). The inter-rater relative error (and intra-class correlation coefficient) ranged from 1.4% to 5.2% (from 0.96 to 0.99). Density of WMH was significantly higher in all four lobes in VD patients compared to controls (p<0.05). Within each group, WMH density was significantly higher in frontal and parietal than in temporal and occipital lobes (p<0.05). CONCLUSION: This landmark based method can accommodate age and disease-related changes in brain morphology. It may be particularly useful for the study of neurodegenerative and cerebrovascular disease and for the validation of template-based automated techniques.","Aged;Alzheimer Disease/ diagnosis/pathology;Brain/anatomy & histology/pathology;Dementia, Vascular/ diagnosis/pathology;Frontal Lobe/anatomy & histology/pathology;Humans;Image Enhancement/ methods;Magnetic Resonance Imaging/ methods;Observer Variation;Occipital Lobe/anatomy & histology/pathology;Parietal Lobe/anatomy & histology/pathology;Pilot Projects;Predictive Value of Tests;Reproducibility of Results;Temporal Lobe/anatomy & histology/pathology","Bokde, A. L.;Teipel, S. J.;Zebuhr, Y.;Leinsinger, G.;Gootjes, L.;Schwarz, R.;Buerger, K.;Scheltens, P.;Moeller, H. J.;Hampel, H.",2002,Feb 15,,0,
5300,Age-associated leukoaraiosis and cortical cholinergic deafferentation,"Objective: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity. Background: One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain. Methods: Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 ± 9.2 years; 55-84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [(11)C]methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated. Results: The severity of periventricular (R = -0.52, p = 0.04) but not nonperiventricular (R = -0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe(R = -0.58, p = 0.02). Conclusions: The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH. Copyright © 2009 by AAN Enterprises.",,"Bohnen, N. I.;Miiller, M. L. T. M.;Kuwabara, H.;Constantine, G. M.;Studenski, S. A.",2009,21,,0,
5301,Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Arabs,"OBJECTIVE: To investigate the Notch 3 mutation spectrum in Arab patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CADASIL, which is an inherited cerebrovascular disease characterized by recurrent subcortical ischemic stroke starting in the third or fourth decade. METHODS: Complete neurological evaluation and sequencing of the Notch 3 gene were carried out at King Faisal Specialist Hospital & Research Centre in 2007 on 2 families from Riyadh, Kingdom of Saudi Arabia and Sudan affected by CADASIL. RESULTS: The index cases had adult onset stroke, vascular dementia, behavioral and psychiatric symptoms and accelerated deaths. In both families, abnormal magnetic resonance imaging findings were detected in symptomatic and asymptomatic individuals. All Notch 3 exons were screened for mutations in both families and no known or novel mutation could be found; although, in one family the brain biopsy showed the typical granular osmiophilic material deposition and the vascular smooth muscle cells. CONCLUSION: This is the first 2 cases of CADASIL in Arabs, which occur without an obvious Notch 3 mutation.","Adult;Aged;Arabs/ genetics;CADASIL/ ethnology/ genetics/pathology;Female;Humans;Male;Middle Aged;Mutation/ genetics;Pedigree;Receptors, Notch/ genetics;Saudi Arabia","Bohlega, S. A.;Abu-Amero, K. K.",2008,Jul,,0,
5302,CADASIL in Arabs: Clinical and genetic findings,"Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs. Methods: We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL. Results: The mean age of onset was 31 ± 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 ± 11. All NOTCH3 exons were screened for mutations, which revealed the presence of previously reported mutations c.406C≥T (p.Arg110≥Cys) in two families (family A&B) and c.475C≥T (p.Arg133≥Cys) mutation in family C. Conclusion: CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups. © 2007 Bohlega et al; licensee BioMed Central Ltd.",epidermal growth factor;Notch3 receptor;adult;amino acid substitution;Arab;article;CADASIL;cerebrovascular accident;chromosome 19;clinical article;clinical feature;controlled study;dementia;depression;disease association;disease exacerbation;female;gene mutation;genotype;human;Kuwait;leukoaraiosis;male;migraine;nuclear magnetic resonance imaging;phenotype;prevalence;risk assessment;risk factor;Saudi Arabia;transient ischemic attack;Yemen,"Bohlega, S.;Al Shubili, A.;Edris, A. A.;Alreshaid, A. A.;AlKhairallah, T. T.;AlSous, M. W.;Farah, S.;Abu-Amero, K. K.",2007,,,0,
5303,Novel mutation of the notch3 gene in arabic family with CADASIL,"Mutations in the NOTCH3 gene are responsible for cerebral autosomal dominant arteri-opathy with subcortical infarcts and leukoen-cephalopathy (CADASIL), an adult onset hereditary angiopathy leading to ischemic stroke, vascular dementia and psychiatric disorders. All mutation of NOTCH3 described so far are striking stereotyped leading to the gain or loss of cystiene residue in a given epidermal growth factor (EGF), like repeat. We report an Arabic family affected with CADASIL mutation, G1790 C, in Exon 11 of the NOTCH3 gene. This is the first novel mutation reported in Arabic CADASIL patients. This finding confirms that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic background. © S. Bohlega., 2011.",genomic DNA;Notch3 receptor;adult;Arab;article;brain damage;CADASIL;case report;clinical feature;dementia;depression;exon;family assessment;family history;gene;gene mutation;genetic association;headache;hemiparesis;human;hyperreflexia;male;migraine;NOTCH3 gene;nuclear magnetic resonance imaging;outcome assessment;paresthesia;pathogenesis;cerebrovascular accident;transient ischemic attack,"Bohlega, S.",2011,,,0,
5304,Diffusion tensor imaging in Huntington's disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits,"White matter (WM) degeneration is an important feature of Huntington's disease (HD) neuropathology. To investigate WM degeneration we used Diffusion Tensor Imaging and Tract-Based Spatial Statistics to compare Fractional Anisotropy, Mean Diffusivity (MD), parallel diffusivity and perpendicular diffusivity (lambda perpendicular) in WM throughout the whole brain in 17 clinically diagnosed HD patients and 16 matched controls. Significant WM diffusivity abnormalities were identified primarily in the corpus callosum (CC) and external/extreme capsules in HD patients compared to controls. Significant correlations were observed between motor symptoms and MD in the CC body, and between global cognitive impairment and lambda perpendicular in the CC genu. Probabilistic tractography from these regions revealed degeneration of functionally relevant interhemispheric WM tracts. Our findings suggest that WM degeneration within interhemispheric pathways plays an important role in the deterioration of cognitive and motor function in HD patients, and that improved understanding of WM pathology early in the disease is required.","Adult;Anisotropy;Brain/ pathology;Cognition Disorders/etiology/ psychology;Corpus Callosum/pathology;Diffusion Tensor Imaging;Disease Progression;Female;Humans;Huntington Disease/ pathology/ psychology;Image Processing, Computer-Assisted;Male;Middle Aged;Models, Statistical;Movement/ physiology;Nerve Degeneration/ pathology;Neuropsychological Tests","Bohanna, I.;Georgiou-Karistianis, N.;Sritharan, A.;Asadi, H.;Johnston, L.;Churchyard, A.;Egan, G.",2011,Sep,10.1007/s11682-011-9121-8,0,
5305,Cerebral amyloid angiopathy with attenuation of the white matter on CT scans: Subcortical arteriosclerotic encephalopathy (Binswanger) in a normotensive patient,"Subcortical arteriosclerotic encephalopathy was diagnosed in a 56-year-old female normotensive patient with gradually progressing dementia, pseudobulbar palsy and motor deficits. CT scan showed white matter low attenuation in the frontal and parietal lobes. Neuropathological examination revealed degeneration of the white matter. Amyloid was found in walls of small cortical vessels. The walls of small vessels in the white matter showed severe thickening, fibrosis and hyalinization but not amyloid. Cerebral amyloid angiopathy may be responsible for subcortical arteriosclerotic encephalopathy.",adult;amyloidosis;autopsy;brain disease;case report;computer analysis;computer assisted tomography;dementia;female;histology;human;priority journal;vascular disease,"Bogucki, A.;Papierz, W.;Szymanska, R.;Staniaszczyk, R.",1988,,,0,
5306,"Thalamic infarcts: Clinical syndromes, etiology, and prognosis","We studied forty patients with CT-proven thalamic infarcts without involvement of the superficial territory of the posterior cerebral artery. The delineation into four arterial thalamic territories (inferolateral, tuberothalamic, posterior choroidal, paramedian) corresponded clinically to four different syndromes. The most common etiologies were lacunar infarction, large artery atherosclerosis with presumed artery-to-artery embolism, cardioembolism, and migrainous stroke. We found no risk factor other than age or oral contraceptive use in six patients. One patient died in the acute phase. During follow-up (45.6 months), the stroke or death rate was 7.4% per year. Delayed pain developed in three patients and abnormal movements in three. Late disability was mainly secondary to persisting neuropsychological dysfunction (thalamic dementia).",adult;aged;brain infarction;clinical article;computer analysis;computer assisted tomography;embolism;female;human;male;priority journal;psychological aspect;thalamus lesion,"Bogousslavsky, J.;Regli, F.;Uske, A.",1988,,,0,
5307,Leukoencephalopathy in patients with ischemic stroke,"Thirty-one (16 women, 15 men; mean age 68 years) of 1,000 consecutive patients with an ischemic stroke investigated systematically with computed tomography (CT), Doppler, electrocardiography (ECG), and biological tests had a diffuse hypodensity of the cerebral hemispheric white matter on CT, a sign indicative of leukoencephalopathy. In 25 of the 31 patients, the acute infarct was deep. Leukoencephalopathy was more frequent in patients with a deep infarct (8%) than in patients in whom the cortex was involved (0.8%) (p < 0.01). A history of progressive intellectual impairment (23%) and the finding of a mild or moderate impairment, or severe dementia (84%) were more frequent in study patients (p < 0.05) than in 31 sex- and age-matched controls with acute infarct of same size and topography but without leukoencephalopathy. A history of hypertension (81%) and high blood pressure on admission (166 ± 19/96 ± 12 mm Hg) were the most common risk factors and were more frequent in study patients (p < 0.05) than in controls. On the other hand, study patients had a ≥ 50% stenosis or occlusion of the carotid artery (13%) less often than controls (35%) (p < 0.05). Diabetes (23%), elevated blood cholesterol (13%) , hematocrit > 45% (23%), smoking (32%), and myocardial ischemia by history or ECG (45%) did not differ. These findings suggest that hypertension may be more strongly associated with leukoencephalopathy than with deep infarcts. In acute stroke patients, leukoencephalopathy on CT should not be considered a fortuitous finding.",adult;aged;central nervous system;clinical article;computer assisted tomography;diagnosis;human;leukoencephalopathy;nervous system;peripheral vascular system;priority journal;cerebrovascular accident,"Bogousslavsky, J.;Regli, F.;Uske, A.",1987,,,0,
5308,Centrum ovale infarcts: subcortical infarction in the superficial territory of the middle cerebral artery,"The centrum ovale, which contains the core of the hemispheric white matter, receives its blood supply from the superficial (pial) middle cerebral artery (MCA) system through perforating medullary branches (MBs), which course toward the lateral ventricles. Though vascular changes in the centrum ovale have been emphasized in dementia, stroke from acute infarction in the centrum ovale is less well documented. We studied 36 patients with infarct limited to MB territory, without involvement of the lenticulostriate territory. Ten patients had a large infarct, associated with severe disease of the ipsilateral carotid artery and with neurologic-neuropsychological impairment not different from that of large MCA infarcts. In 26 patients, the infarct was small and round or ovoid, and was associated with hypertension or diabetes and with ""lacunar syndromes,"" usually of progressive onset. These findings show that two forms of centrum ovale infarcts can be delineated according to infarct size and shape, clinical picture, risk factors, and associated vascular disease. We propose to classify subcortical infarcts in the carotid system into four main territory groups: (1) deep perforator territory (from the MCA trunk, carotid siphon, anterior choroidal artery, anterior cerebral artery trunk, Heubner's artery, and posterior communicating artery); (2) perforating MB territory (from the superficial MCA branches); (3) junctional (territory between 1 and 2); and (4) combined territories.","Aged;Brain/*pathology;Cerebral Infarction/*diagnosis/etiology/radiography;Female;Humans;*Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Tomography, X-Ray Computed","Bogousslavsky, J.;Regli, F.",1992,Oct,,0,
5309,Acute multiple infarction involving the anterior circulation,"OBJECTIVE: To evaluate the frequency and clinical, topographic, and etiologic patterns of acute multiple infarction involving the anterior circulation. DESIGN: Data analysis from a prospective acute stroke registry in a community-based primary care center. RESULTS: Among 751 patients with first ischemic stroke in the anterior circulation over a 4-year period, 40 patients (5%) had acute multiple infarcts involving the anterior circulation. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were four topographic patterns of infarction: (1) superficial infarcts (11 patients [28%]); (2) superficial and deep infarcts (12 patients [30%]); (3) deep infarcts (three patients [8%]); and (4) infarcts involving the anterior and the posterior circulation (14 patients [35%]). Both cerebral hemispheres were involved in one fourth of the cases. A specific clinical picture was found in up to 20% of the patients. This included global aphasia with left hemianopia, hemisensory loss or hemiparesis (in right-handed patients), transcortical mixed aphasia with hemianopia, and acute pure cognitive impairment (""dementia""). Large-artery disease was found in 13 patients (33%); a cardiac source of embolism was found in 11 patients (28%); and both were found in three patients (8%). Bilateral infarcts were related to cardioembolism (four patients) and bilateral large-artery disease (three patients). One month after stroke, one fourth of the patients were independent, one third had some disability, and 40% were either dead or completely dependent. CONCLUSIONS: Acute multiple infarcts involving the anterior circulation may be bilateral more frequently than is currently thought, and they are often associated with posterior circulation infarcts. They mainly involve the pial hemispheral territories, commonly being caused by cardioembolism or bilateral carotid atheroma. They may be associated with a specific neurologic-neuropsychological dysfunction pattern in up to one fifth of the patients, allowing diagnosis before brain imaging.","Adult;Aged;Aged, 80 and over;Cerebral Infarction/diagnosis/etiology/ physiopathology;Cerebrovascular Circulation;Female;Follow-Up Studies;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nervous System/physiopathology;Prospective Studies;Registries;Risk Factors;Tomography, X-Ray Computed","Bogousslavsky, J.;Bernasconi, A.;Kumral, E.",1996,Jan,,0,
5310,Full diffusion characterization implicates regionally disparate neuropathology in mild cognitive impairment,"Diffusion tensor imaging (DTI) is used to detect tissue pathology. In Alzheimer's disease (AD) research, DTI has been used to elucidate differences in disease stages and to track progression over time and clinical severity. Many of these studies have identified the fornix as particularly vulnerable in the early stages of pathology associated with memory decline in prodromal AD. Emerging research suggests principal tensor components, axial (DA) and radial (DR) diffusivity, are more sensitive to underlying tissue pathology than are mean diffusivity (MD) and fractional anisotropy (FA). Given the established regionally specific tissue decline in MCI, we examined components of the full diffusion tensor (MD, FA, DR, and DA) for sensitivity to regional pathology associated with specific memory deficits in 18 individuals with MCI. We investigated multiple regions of interest, including fornix, temporal stem, and control regions for association with severity of impairment on multiple memory measures, including a type of neuropsychological task shown to be particularly sensitive to early memory decline in MCI. Better paired associate learning was selectively associated with lower DA (beta = -0.663, p = 0.003), but not with DR, MD, or FA of the temporal stems. Conversely, better paired associate learning was associated with lower DR (beta = -0.523, p = 0.026), higher FA (beta = 0.498, p = 0.036), and lower MD (beta = -0.513, p = 0.030), but not DA in the fornix. No association was found for control regions, or for control cognitive measures. These findings suggest disparate pathology of temporal stems and fornix white matter in association with early memory impairment in MCI. Further, they highlight the methodological importance of evaluating the full tensor, rather than only summative metrics in research using DTI.","Aged;Alzheimer Disease/ pathology;Anisotropy;Brain/ pathology;Brain Mapping;Diffusion Tensor Imaging;Female;Functional Laterality/physiology;Humans;Male;Mild Cognitive Impairment/ pathology;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Psychiatric Status Rating Scales","Boespflug, E. L.;Storrs, J.;Sadat-Hossieny, S.;Eliassen, J.;Shidler, M.;Norris, M.;Krikorian, R.",2014,Jan,10.1007/s00429-013-0506-x,0,
5311,MR Imaging-based Multimodal Autoidentification of Perivascular Spaces (mMAPS): Automated Morphologic Segmentation of Enlarged Perivascular Spaces at Clinical Field Strength,"Purpose To describe a fully automated segmentation method that yields object-based morphologic estimates of enlarged perivascular spaces (ePVSs) in clinical-field-strength (3.0-T) magnetic resonance (MR) imaging data. Materials and Methods In this HIPAA-compliant study, MR imaging data were obtained with a 3.0-T MR imager in research participants without dementia (mean age, 85.3 years; range, 70.4-101.2 years) who had given written informed consent. This method is built on (a) relative normalized white matter, ventricular and cortical signal intensities within T1-weighted, fluid-attenuated inversion recovery, T2-weighted, and proton density data and (b) morphologic (width, volume, linearity) characterization of each resultant cluster. Visual rating was performed by three raters, including one neuroradiologist, after established single-section guidelines. Correlations between visual counts and automated counts, as well session-to-session correlation of counts within each participant, were assessed with the Pearson correlation coefficient r. Results There was a significant correlation between counts by visual raters and automated detection of ePVSs in the same section (r = 0.65, P < .001; r = 0.69, P < .001; and r = 0.54, P < .01 for raters 1, 2, and 3, respectively). With regard to visual ratings and whole-brain count consistency, average visual rating scores were highly correlated with automated detection of total burden volume (r = 0.58, P < .01) and total ePVS number (r = 0.76, P < .01). Morphology of clusters across 28 data sets was consistent with published radiographic estimates of ePVS; mean width of clusters segmented was 3.12 mm (range, 1.7-13.5 mm). Conclusion This MR imaging-based method for multimodal autoidentification of perivascular spaces yields individual whole-brain morphologic characterization of ePVS in clinical MR imaging data and is an important tool in the detailed assessment of these features. ((c)) RSNA, 2017 Online supplemental material is available for this article.",,"Boespflug, E. L.;Schwartz, D. L.;Lahna, D.;Pollock, J.;Iliff, J. J.;Kaye, J. A.;Rooney, W.;Silbert, L. C.",2018,Feb,,0,
5312,Associative learning and regional white matter deficits in mild cognitive impairment,"BACKGROUND: While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration.OBJECTIVE: Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements.METHODS: DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks.RESULTS: Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI",,"Boespflug, E. L.",2014,2014,,0,
5313,A new visual rating scale to assess strategic white matter hyperintensities within cholinergic pathways in dementia,"BACKGROUND AND PURPOSE: One possible mechanism of cognitive decline in individuals with subcortical vascular disease is disruption of cholinergic fibers by ischemic lesions, such as strategically located white matter hyperintensities (WMH). The authors applied a new MRI visual rating scale to assess WMH within cholinergic pathways in patients with Alzheimer Disease (AD) and subcortical ischemic microvascular disease. METHODS: Subjects included 60 AD patients with and without WMH, matched for age, as well as 15 control subjects. A visual rating scale was developed based on published immunohistochemical tracings of the cholinergic pathways in humans. On 4 selected axial images, the severity of WMH in the cholinergic pathways was rated on a 3-point scale for ten regions, identified with major anatomical landmarks. A published, consensus-derived, general WMH scale was also applied. All subjects underwent standardized neuropsychological testing. RESULTS: The Cholinergic Pathways HyperIntensities Scale showed reliability and was validated with volumetry of strategic WMH. After accounting for age and education in a multiple linear regression model, The Cholinergic Pathways HyperIntensities Scale ratings were associated with impaired performance on the Mattis Dementia Rating Scale (r=0.40; P=0.02) and accounted for 12% of the variance (corrected r2). A similar model was not significant for general WMH scores. CONCLUSIONS: The new MRI rating scale for WMH in cholinergic pathways is reliable and shows stronger correlations with cognitive performance than a general WMH rating scale in AD with WMH. This new rating scale provides indirect evidence that localization of WMH within neurotransmitter systems may contribute to cognitive decline.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;Brain/ pathology;Case-Control Studies;Dementia, Vascular/ diagnosis/pathology;Female;Humans;Immunohistochemistry;Ischemia/pathology;Leukoaraiosis;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Microcirculation/pathology;Models, Statistical;Neurons/metabolism;Neuropsychological Tests;Neurotransmitter Agents/metabolism;Receptors, Cholinergic/ metabolism;Severity of Illness Index;Time Factors;Visual Perception","Bocti, C.;Swartz, R. H.;Gao, F. Q.;Sahlas, D. J.;Behl, P.;Black, S. E.",2005,Oct,10.1161/01.STR.0000183615.07936.b6,0,
5314,Vascular Cognitive Impairment: Most Useful Subtests of the Montreal Cognitive Assessment in Minor Stroke and Transient Ischemic Attack,"Background/Aims: Cognitive impairment is frequent in cerebrovascular disease but often remains undetected. The Montreal Cognitive Assessment (MoCA) has been proposed in this context. Our aim was to evaluate the MoCA and its subtests in cerebrovascular disease. Methods: We assessed 386 consecutive patients with minor stroke (National Institutes of Health Stroke Score <4) or transient ischemic attack at 3 months. The MoCA and the modified Rankin Scale (mRS) were administered. Computed tomography (CT) scans were assessed for stroke and white matter changes. An unfavorable functional outcome was defined as mRS >1. Results: The prevalence of cognitive impairment (cutoff of 26) was 55% using the MoCA and 13% using the MMSE. In a multivariate analysis, MoCA <26 was associated with the outcome (OR 3.00, CI 1.78-5.03), as were remote lacunar stroke on CT and white matter changes of at least moderate severity. Five subtests (5-word recall, word list generation, trail-making, abstract reasoning and cube copy) formed an optimal short MoCA with 6/10 or less showing a sensitivity of 91% and a specificity of 83%. Conclusion: This study extends the utility of the MoCA to milder forms of cerebrovascular disease. The MoCA is associated with the 3-month functional outcome. Five subtests may constitute an optimal brief tool in vascular cognitive impairment.",abstract reasoning test;acute coronary syndrome;aged;article;cerebrovascular accident;cognitive defect;computer assisted tomography;cube copy test;female;functional assessment;human;lacunar stroke;major clinical study;male;Mini Mental State Examination;Montreal cognitive assessment;National Institutes of Health Stroke Scale;neuroimaging;neuropsychological test;priority journal;psychologic test;Rankin scale;transient ischemic attack;verbal fluency test;white matter;word list recall;word recognition,"Bocti, C.;Legault, V.;Leblanc, N.;Berger, L.;Nasreddine, Z.;Beaulieu-Boire, I.;Yaneva, K.;Boulanger, J. M.",2013,,,0,
5315,HIV-associated neurodegeneration and neuroimmunity: multivoxel MR spectroscopy study in drug-naïve and treated patients,"Objectives: The aim of this study was to test neurobiochemical changes in normal appearing brain tissue in HIV+ patients receiving and not receiving combined antiretroviral therapy (cART) and healthy controls, using multivoxel MR spectroscopy (mvMRS). Methods: We performed long- and short-echo 3D mvMRS in 110 neuroasymptomatic subjects (32 HIV+ subjects on cART, 28 HIV+ therapy-naïve subjects and 50 healthy controls) on a 3T MR scanner, targeting frontal and parietal supracallosal subcortical and deep white matter and cingulate gyrus (NAA/Cr, Cho/Cr and mI/Cr ratios were analysed). The statistical value was set at p < 0.05. Results: Considering differences between HIV-infected and healthy subjects, there was a significant decrease in the NAA/Cr ratio in HIV+ subjects in all observed locations, an increase in mI/Cr levels in the anterior cingulate gyrus (ACG), and no significant differences in Cho/Cr ratios, except in ACG, where the increase showed trending towards significance in HIV+ patients. There were no significant differences between HIV+ patients on and without cART in all three ratios. Conclusion: Neuronal loss and dysfunction affects the whole brain volume in HIV-infected patients. Unfortunately, cART appears to be ineffective in halting accelerated neurodegenerative process induced by HIV but is partially effective in preventing glial proliferation. Key Points: • This is the first multivoxel human brain 3T MRS study in HIV.• All observed areas of the brain are affected by neurodegenerative process.• Cingulate gyrus and subcortical white matter are most vulnerable to HIV-induced neurodegeneration.• cART is effective in control of inflammation but ineffective in preventing neurodegeneration.",anterior cingulate;brain size;brain tissue;cell proliferation;chronic brain disease;controlled study;highly active antiretroviral therapy;HIV associated dementia;human;Human immunodeficiency virus infected patient;inflammation;major clinical study;nerve degeneration;normal human;nuclear magnetic resonance scanner;nuclear magnetic resonance spectroscopy;prevention;white matter,"Boban, J.;Kozic, D.;Turkulov, V.;Ostojic, J.;Semnic, R.;Lendak, D.;Brkic, S.",2017,,10.1007/s00330-017-4772-5,0,
5316,The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson's disease,"OBJECTIVES: White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson's disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. PATIENTS AND METHODS: 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. RESULTS: Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8cm(3)+/-18.836 vs. 9.3cm(3)+/-12.2; p=0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p=0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p=0.006; R(2)=0.40) after correction for age. CONCLUSIONS: Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.",Cognition;Deep brain stimulation;Parkinson;Parkinson dementia;Subthalamic nucleus;White matter lesions,"Blume, J.;Lange, M.;Rothenfusser, E.;Doenitz, C.;Bogdahn, U.;Brawanski, A.;Schlaier, J.",2017,Aug,,0,
5317,Memory after silent stroke: Hippocampus and infarcts both matter,"Objective: Memory decline commonly occurs among elderly individuals. This observation is often attributed to early neurodegenerative changes in the hippocampus and related brain regions. However, the contribution of vascular lesions, such as brain infarcts, to hippocampal integrity and age-associated memory decline remains unclear. Methods: We studied 658 elderly participants without dementia from a prospective, communitybased study on aging and dementia who received high-resolution structural MRI. Cortical and subcortical infarcts were identified, and hippocampal and relative brain volumes were calculated following standard protocols. Summary scores reflecting performance on tasks of memory, language, processing speed, and visuospatial function were derived from a comprehensive neuropsychological battery. We used multiple regression analyses to relate cortical and subcortical infarcts, hippocampal and relative brain volume, to measures of cognitive performance in domains of memory, language, processing speed, and visuospatial ability. Results: Presence of brain infarcts was associated with a smaller hippocampus. Smaller hippocampus volume was associated with poorer memory specifically. Brain infarcts were associated with poorer memory and cognitive performance in all other domains, which was independent of hippocampus volume. Conclusions: Both hippocampal volume and brain infarcts independently contribute to memory performance in elderly individuals without dementia. Given that age-associated neurodegenerative conditions, such as Alzheimer disease, are defined primarily by impairment in memory, these findings have clinical implications for prevention and for identification of pathogenic factors associated with disease symptomatology. Copyright © 2012 by AAN Enterprises, Inc.",aged;article;brain infarction;brain size;cognition;depth perception;disease association;female;hippocampus;human;language;major clinical study;male;memory;memory disorder;nuclear magnetic resonance imaging;priority journal;scoring system;cerebrovascular accident,"Blum, S.;Luchsinger, J. A.;Manly, J. J.;Schupf, N.;Stern, Y.;Brown, T. R.;DeCarli, C.;Small, S. A.;Mayeux, R.;Brickman, A. M.",2012,,,0,
5318,Normal pressure hydrocephalus,"Normal pressure hydrocephalus is a clinical syndrome associated with dementia, urinary incontinence, gait apraxia and computed tomography or magnetic resonance imaging evidence of communicating hydrocephalus. In the elderly patient, these symptoms may be overlooked or discounted if the clinician is not well versed in this condition. Normal pressure hydrocephalus has classically been described as an idiopathic disorder. Recent studies indicate that this syndrome may be associated with deep white matter infarction. This article discusses the case of a patient who suffered from this condition. Clinical information is presented.",,"Blomerth, P. R.",1993,1993,,0,
5319,Higher subcortical and white matter cerebral blood flow in perinatally HIV-infected children,"This study aimed to evaluate cerebral blood flow (CBF) in pediatric human immunodeficiency virus (HIV)-infection, and its role in HIVrelated cerebral injury and cognitive impairment. This cross-sectional observational study compared 28 perinatally HIV-infected children (8-18 years) to 34 healthy controls matched for age, sex, ethnicity, and socio-economic status. All participants underwent 3-Tesla magnetic resonance imaging, using arterial spin labeling to assess CBF in gray matter (GM), white matter (WM), basal ganglia, and thalamus. We used linear regression analysis to evaluate group differences and associations with HIV disease and treatment characteristics, macrostructural (volume loss, WM lesions) or microstructural injury (increased WM diffusivity, neurometabolite alterations), or poorer cognitive performance. HIV-infected children had higher CBF in WM (+10.2%; P=0.042), caudate nucleus (+4.8%; P=0.002), putamen (+3.6%; P= 0.017), nucleus accumbens (+3.9%; P=0.031), and thalamus (+5.5%; P=0.032). Thalamus CBF was highest in children with a Centers for Disease Control and Prevention stage B (Coef.=6.45; P=0.005) or C (Coef.=8.52; P=0.001) diagnosis. LowerGMCBF was associated with higher WM lesion volume in HIV-infected children (Coef.=-0.053; P=0.001). No further associations with HIVrelated cognitive impairment or cerebral injury were found. CBF was higher in WM, basal ganglia, and thalamus in combination antiretroviral therapy (cART)-treated perinatally HIV-infected children, but this was not associated with cerebral injury or cognitive impairment. HIV-infected children with lower GM CBF had a higher volume of WM lesions, which could reflect vascular disease as potential contributing factor to white matter injury. Lifelong exposure to HIV and cART in this population warrants longitudinal assessment of CBF and how it relates to (neuro)inflammation, vascular dysfunction, and cerebral injury in pediatric HIV.",anti human immunodeficiency virus agent;adolescent;adult;age;antiretroviral therapy;arterial spin labeling;article;basal ganglion;brain blood flow;brain circulation;brain injury;brain size;caudate nucleus;cerebrovascular disease;child;clinical article;cognition;cognitive defect;controlled study;cross-sectional study;disease association;ethnicity;female;gray matter;HIV associated dementia;human;Human immunodeficiency virus infected patient;Human immunodeficiency virus infection;image processor;imaging software;male;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;nucleus accumbens;observational study;perinatal infection;priority journal;putamen;sex;social status;subcortex;thalamus;white matter;white matter injury;white matter lesion;Freesurfer;Ingenia;Statistical Parametric Mapping,"Blokhuis, C.;Mutsaerts, H. J. M. M.;Cohen, S.;Scherpbier, H. J.;Caan, M. W. A.;Majoie, C. B. L. M.;Kuijpers, T. W.;Reiss, P.;Wit, F. W. N. M.;Pajkrt, D.",2017,,10.1097/md.0000000000005891,0,
5320,The eye as a window to the brain: Neuroretinal thickness is associated with microstructural white matter injury in HIV-infected children,"PURPOSE. Despite combination antiretroviral therapy (cART), perinatal HIV-infection can cause decreased gray and white matter volume, microstructural white matter injury, and retinal structural abnormalities. As neuroretinal tissue is directly connected to the brain, these deficits may have a shared pathogenesis. We aimed to assess associations between neuroretinal thickness and cerebral injury in cART-treated perinatally HIV-infected children and healthy controls. METHODS. This cross-sectional observational study included 29 cART-treated perinatally HIVinfected children and 35 matched healthy controls. All participants underwent 3.0 Tesla magnetic resonance imaging (MRI), determining gray and white matter volumes from T1weighted sequences, and white matter diffusivity using diffusion tensor imaging (DTI). Regional individual and total neuroretinal layer thickness was quantified using spectraldomain optical coherence tomography. We explored associations between retinal and cerebral parameters using multivariable linear regression analysis. RESULTS. In HIV-infected children, lower foveal and pericentral neuroretinal thickness was associated with damaged white matter microstructure, in terms of lower fractional anisotropy and higher mean and radial diffusivity. In healthy controls only, neuroretinal thickness was associated with gray and white matter volume. CONCLUSIONS. Decreased neuroretinal thickness is associated with microstructural white matter injury, but not with lower cerebral volume in HIV-infected children. This suggests that HIV-induced retinal thinning and microstructural white matter injury may share a common pathogenesis, and longitudinal assessment of neuroretinal alterations in parallel with MRI and neuroinflammatory markers may further our insight into the pathogenesis of HIV-induced cerebral injury in children.",adolescent;article;brain injury;CD4 lymphocyte count;child;clinical article;controlled study;correlation analysis;cross-sectional study;diffusion tensor imaging;female;fractional anisotropy;highly active antiretroviral therapy;HIV associated dementia;human;Human immunodeficiency virus infection;information processing;male;multiple linear regression analysis;Netherlands;neuroretinal thickness;nuclear magnetic resonance imaging;observational study;priority journal;retina degeneration;retina injury;social status;spectral domain optical coherence tomography;visual system parameters;white matter injury,"Blokhuis, C.;Demirkaya, N.;Cohen, S.;Wit, F. W. N. M.;Scherpbier, H. J.;Reiss, P.;Abramoff, M. D.;Caan, M. W. A.;Majoie, C. B. L. M.;Verbraak, F. D.;Pajkrt, D.",2016,,10.1167/iovs.16-19716,0,
5321,Identification and characterization of Huntington related pathology: an in vivo DKI imaging study,"An important focus of Huntington Disease (HD) research is the identification of symptom-independent biomarkers of HD neuropathology. There is an urgent need for reproducible, sensitive and specific outcome measures, which can be used to track disease onset as well as progression. Neuroimaging studies, in particular diffusion-based MRI methods, are powerful probes for characterizing the effects of disease and aging on tissue microstructure. We report novel diffusional kurtosis imaging (DKI) findings in aged transgenic HD rats. We demonstrate altered diffusion metrics in the (pre)frontal cerebral cortex, external capsule and striatum. Presence of increased diffusion complexity and restriction in the striatum is confirmed by an increased fiber dispersion in this region. Immunostaining of the same specimens reveals decreased number of microglia in the (pre)frontal cortex, and increased numbers of oligodendrocytes in the striatum. We conclude that DKI allows sensitive and specific characterization of altered tissue integrity in this HD rat model, indicating a promising potential for diagnostic imaging of gray and white matter pathology.","Animals;Brain/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Disease Models, Animal;Huntington Disease/ pathology;Image Processing, Computer-Assisted/ methods;Immunohistochemistry;Male;Rats;Rats, Transgenic","Blockx, I.;Verhoye, M.;Van Audekerke, J.;Bergwerf, I.;Kane, J. X.;Delgado, Y. P. R.;Veraart, J.;Jeurissen, B.;Raber, K.;von Horsten, S.;Ponsaerts, P.;Sijbers, J.;Leergaard, T. B.;Van der Linden, A.",2012,Nov 1,10.1016/j.neuroimage.2012.06.032,0,
5322,Genotype specific age related changes in a transgenic rat model of Huntington's disease,"We aimed to characterize the transgenic Huntington rat model with in vivo imaging and identify sensitive and reliable biomarkers associated with early and progressive disease status. In order to do so, we performed a multimodality (DTI and PET) longitudinal imaging study, during which the same TgHD and wildtype (Wt) rats were repetitively scanned. Surprisingly, the relative ventricle volume was smaller but increased faster in TgHD compared to Wt animals. DTI (mean, axial, radial diffusivity) revealed subtle genotype-specific aging effects in the striatum and its surrounding white matter, already in the presymptomatic stage. Using (1)(8)F-FDG and (1)(8)F-Fallypride PET imaging, we were not able to demonstrate genotype-specific aging effects within the striatum. The outcome of this longitudinal study was somewhat surprising as it demonstrated a significant differential aging pattern in TgHD versus Wt animals. Although it seems that the TgHD rat model does not have a sufficient expression of disease yet at the age of 12 months, further validation of this model is highly beneficial since there is still an incomplete understanding of the early disease mechanisms of Huntington's disease.","Aging/ pathology;Animals;Autoradiography;Benzamides;Biomarkers;Brain/pathology/radionuclide imaging;Cerebral Ventricles/pathology/radionuclide imaging;Corpus Striatum/pathology/radionuclide imaging;Diffusion Tensor Imaging;Fluorodeoxyglucose F18;Genotype;Huntington Disease/ genetics/pathology/radionuclide imaging;Image Processing, Computer-Assisted;Male;Phenotype;Positron-Emission Tomography;Pyrrolidines;Radiopharmaceuticals;Rats;Rats, Transgenic","Blockx, I.;Van Camp, N.;Verhoye, M.;Boisgard, R.;Dubois, A.;Jego, B.;Jonckers, E.;Raber, K.;Siquier, K.;Kuhnast, B.;Dolle, F.;Nguyen, H. P.;Von Horsten, S.;Tavitian, B.;Van der Linden, A.",2011,Oct 15,10.1016/j.neuroimage.2011.07.007,0,
5323,MRI of cerebral microhemorrhages,"OBJECTIVE. The purpose of this pictorial essay is to discuss the differential diagnosis of cerebral microhemorrhages on T2*-weighted gradient-echo MRI. CONCLUSION. Cerebral amyloid angiopathy and chronic systemic hypertension are the two most common causes of cerebral microhemorrhages. Less common causes include diffuse axonal injury, cerebral embolism, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, multiple cavernous malformations, vasculitis, hemorrhagic micrometastasis, radiation vasculopathy, and Parry-Romberg syndrome. © American Roentgen Ray Society.",article;axonal injury;brain hemorrhage;CADASIL;cerebrovascular disease;human;nuclear magnetic resonance imaging;priority journal;vascular amyloidosis,"Blitstein, M. K.;Tung, G. A.",2007,,,0,
5324,White-matter lesions on CT in Alzheimer patients: relation to clinical symptomatology and vascular factors,"Fifty-four patients with Alzheimer's disease (AD) were examined for white-matter lesions (WMLs) using computerized tomography. WMLs were more frequent in late-onset AD (LAD) (26/34-76%) than in early-onset AD (EAD) (5/20-25%) (p less than 0.0001), in AD without parietal predominance (10/11-91%) (p less than 0.005) than in AD with parietal predominance (5/15-33%), and in AD with confusional symptoms (11/12-92%) than in AD without confusional symptoms (4/14-29%) (p less than 0.001). The supine systolic blood pressure was higher in AD with WMLs (151 +/- 20) than in AD without WML (139 +/- 22) (p less than 0.05). AD patients with WMLs, but not those without WMLs, had a higher mean albumin ratio (7.5 +/- 2.7) than healthy controls (5.7 +/- 2.1) (p +/- 0.005). The finding of less focal (= less parietal) symptomatology in AD with WMLs than without WMLs suggests clinical significance of WMLs in AD, while the relations between blood pressure, BBB function and WMLs support the hypothesis of a vascular pathogenesis.","Aged;Alzheimer Disease/*radiography;Blood-Brain Barrier/*physiology;Brain/*radiography;Brain Damage, Chronic/radiography;Cerebral Infarction/*radiography;Diffuse Cerebral Sclerosis of Schilder/*radiography;Female;Humans;Male;Neuropsychological Tests;*Tomography, X-Ray Computed","Blennow, K.;Wallin, A.;Uhlemann, C.;Gottfries, C. G.",1991,Mar,,0,
5325,Conversion from mild cognitive impairment to dementia: influence of folic acid and vitamin B12 use in the VITA cohort,"OBJECTIVE: Increased serum homocysteine and low folate levels are associated with a higher rate of conversion to dementia. This study examined the influence of vitamin B12/folic acid intake on the conversion from mild cognitive impairment (MCI) to dementia. PARTICIPANTS: A community dwelling cohort of older adults (N=81) from the Vienna Transdanube aging study with MCI. DESIGN: Prospective study with a retrospective evaluation of vitamin intake. MEASUREMENTS: Laboratory measurements, brain magnetic resonance imaging, and cognitive functioning were assessed at baseline and at five-year follow-up. RESULTS: The self-reported combined use of folic acid and vitamin B12 for more than one year was associated with a lower conversion rate to dementia. Serum levels of homocysteine and vitamin B12 as measured at baseline or at five years were not associated with conversion. Higher folate levels at baseline in females predicted a lower conversion rate to dementia. The assessment of brain morphological parameters by magnetic resonance imaging revealed higher serum folate at baseline, predicting lower medial temporal lobe atrophy and higher levels of homocysteine at baseline, predicting moderate/severe global brain atrophy at five years. Users of vitamin B12 or folate, independent of time and pattern of use, had lower grades of periventricular hyperintensities and lower grades of deep white matter lesions as compared to non-users. CONCLUSIONS: These results from a middle European study support observations on the protective ability of folate in MCI patients with respect to conversion to dementia; they also point to a participation of homocysteine metabolism on processes associated with brain atrophy.",Aged;Aging;Atrophy;Austria;Brain/growth & development/pathology;Cohort Studies;Dementia/etiology/ prevention & control;Dietary Supplements;Disease Progression;Female;Folic Acid/administration & dosage/blood/ therapeutic use;Follow-Up Studies;Humans;Hyperhomocysteinemia/blood/complications/diet therapy/physiopathology;Longitudinal Studies;Male;Mild Cognitive Impairment/blood/complications/ diet therapy/physiopathology;Prospective Studies;Retrospective Studies;Vitamin B 12/administration & dosage/blood/ therapeutic use,"Blasko, I.;Hinterberger, M.;Kemmler, G.;Jungwirth, S.;Krampla, W.;Leitha, T.;Heinz Tragl, K.;Fischer, P.",2012,Aug,10.1007/s12603-012-0051-y,0,
5326,Cognitive dysfunction and dementia in primary Sjögren's syndrome,"Background. Primary Sjögren's syndrome (PSS) is a frequent systemic autoimmune disease. In this study, we aimed to explore the cognitive impairment and the correlations with brain MRI. Methods. Twenty-five patients (mean age 55 ± 11.8 years, 21 females) with PSS were prospectively selected and tested with a French translation of the Brief Repeatable Battery for Neuropsychological Examination. The results were compared with the scores for 25 matched patients with multiple sclerosis (MS) and 25 controls. Brain lesions were assessed by brain MRI using the Wahlund classification. Results. Fifteen of the 25 PSS patients (60%) presented with cognitive disorders versus 19/25 MS patients (76%). Five patients had dementia in the PSS group. Speed of information processing, attention, immediate and long-term memory, and executive functions were frequently impaired. The mean duration of cognitive complaints was 5.6 ± 6.1 years, and the mean duration of PSS was 15.8 ± 14.0 years. A trend towards a correlation was found between the severity of cognitive impairment and the degree of white matter lesions (WML) (P=0.03, rho = 0.43). Conclusion. Cognitive impairment - mild or dementia - exists in patients with PSS. Further MRI studies are needed to better understand the precise neural basis of cognitive impairment in PSS patients. © 2013 Frederic Blanc et al.",adult;article;attention;brain damage;clinical article;cognitive defect;controlled study;dementia;disease severity;executive function;female;human;long term memory;male;multiple sclerosis;neuropsychological test;nuclear magnetic resonance imaging;prospective study;short term memory;Sjoegren syndrome;white matter lesion,"Blanc, F.;Longato, N.;Jung, B.;Kleitz, C.;Di Bitonto, L.;Cretin, B.;Collongues, N.;Sordet, C.;Fleury, M.;Poindron, V.;Gottenberg, J. E.;Anne, O.;Lipsker, D.;Martin, T.;Sibilia, J.;De Seze, J.",2013,,,0,
5327,Cognitive Dysfunction and Dementia in Primary Sjogren's Syndrome,"Background. Primary Sjogren's syndrome (PSS) is a frequent systemic autoimmune disease. In this study, we aimed to explore the cognitive impairment and the correlations with brain MRI. Methods. Twenty-five patients (mean age 55 +/- 11.8 years, 21 females) with PSS were prospectively selected and tested with a French translation of the Brief Repeatable Battery for Neuropsychological Examination. The results were compared with the scores for 25 matched patients with multiple sclerosis (MS) and 25 controls. Brain lesions were assessed by brain MRI using the Wahlund classification. Results. Fifteen of the 25 PSS patients (60%) presented with cognitive disorders versus 19/25 MS patients (76%). Five patients had dementia in the PSS group. Speed of information processing, attention, immediate and long-term memory, and executive functions were frequently impaired. The mean duration of cognitive complaints was 5.6 +/- 6.1 years, and the mean duration of PSS was 15.8 +/- 14.0 years. A trend towards a correlation was found between the severity of cognitive impairment and the degree of white matter lesions (WML) (P = 0.03, rho = 0.43). Conclusion. Cognitive impairment-mild or dementia-exists in patients with PSS. Further MRI studies are needed to better understand the precise neural basis of cognitive impairment in PSS patients.",,"Blanc, F.;Longato, N.;Jung, B.;Kleitz, C.;Di Bitonto, L.;Cretin, B.;Collongues, N.;Sordet, C.;Fleury, M.;Poindron, V.;Gottenberg, J. E.;Anne, O.;Lipsker, D.;Martin, T.;Sibilia, J.;de Seze, J.",2013,,10.1155/2013/501327,0,
5328,"Preventing cognitive decline and dementia from cerebral small vessel disease: The LACI-1 Trial. Protocol and statistical analysis plan of a phase IIa dose escalation trial testing tolerability, safety and effect on intermediary endpoints of isosorbide mononitrate and cilostazol, separately and in combination","Rationale The pathophysiology of most lacunar stroke, a form of small vessel disease, is thought to differ from large artery atherothrombo- or cardio-embolic stroke. Licensed drugs, isosorbide mononitrate and cilostazol, have promising mechanisms of action to support their testing to prevent stroke recurrence, cognitive impairment, or radiological progression after lacunar stroke. Aim LACI-1 will assess the tolerability, safety, and efficacy, by dose, of isosorbide mononitrate and cilostazol, alone and in combination, in patients with ischemic lacunar stroke. Sample size A sample of 60 provides 80+% power (significance 0.05) to detect a difference of 35% (90% versus 55%) between those reaching target dose on one versus both drugs. Methods and design LACI-1 is a phase IIa partial factorial, dose-escalation, prospective, randomized, open label, blinded endpoint trial. Participants are randomized to isosorbide mononitrate and/or cilostazol for 11 weeks with dose escalation to target as tolerated in two centers (Edinburgh, Nottingham). At three visits, tolerability, safety, blood pressure, pulse wave velocity, and platelet function are assessed, plus magnetic resonance imaging to assess cerebrovascular reactivity in a subgroup. Study outcomes Primary: proportion of patients completing study achieving target maximum dose. Secondary symptoms whilst taking medications; safety (hemorrhage, recurrent vascular events, falls); blood pressure, platelet function, arterial stiffness, and cerebrovascular reactivity. Discussion This study will inform the design of a larger phase III trial of isosorbide mononitrate and cilostazol in lacunar stroke, whilst providing data on the drugs' effects on vascular and platelet function. Trial registration ISRCTN (ISRCTN12580546) and EudraCT (2015-001953-33).",Lacunar stroke;blood-brain barrier;cerebrovascular reactivity;cilostazol;endothelium;isosorbide mononitrate;small vessel disease;white matter hyperintensities,"Blair, G. W.;Appleton, J. P.;Law, Z. K.;Doubal, F.;Flaherty, K.;Dooley, R.;Shuler, K.;Richardson, C.;Hamilton, I.;Shi, Y.;Stringer, M.;Boyd, J.;Thrippleton, M. J.;Sprigg, N.;Bath, P. M.;Wardlaw, J. M.",2017,Jan 1,,0,
5329,"Cerebral microangiopathy - Pathophysiology, clinical findings and therapy","White matter changes due to cerebral microangiopathy are frequently seen on magnetic resonance imaging in the brain of elderly persons. If they reach a certain level, they represent not only an incidental imaging finding but a serious medical condition. Referred to as Subcortical Vascular Encephalopathy"" (SVE), progressive psychomotor slowing and disturbances of executive functions towards the development of dementia as well as characteristic gait disturbances with falls occur. These symptoms can be explained primarily by an interruption of functionally important neuronal circuits connecting the prefrontal cortex with the basal ganglia, which are involved in the executive control of cognitive functions and motor control. © Georg Thieme Verlag KG Stuttgart, New York.",,"Blahak, C.;Ebert, A.;Schäfer, A.",2012,2012,,0,
5330,"Vascular cognitive impairment: Epidemiology, subtypes, diagnosis and management","Dementia occurs after stroke in 25% of patients but also can arise from covert cerebrovascular disease (CVD). 'Silent' lacunes occur in 25% of the elderly, often associated with focal or confluent hyperintensities on T2-weighted magnetic resonance imaging, which are detected in 95% of seniors. These covert infarcts predict future stroke and faster cognitive decline. Best practice guidelines advocate screening for cognitive impairment in all phases of overt stroke, when covert CVD is uncovered, when vascular risk factors are present and if patients present with cognitive complaints. Standardised testing is recommended, emphasising executive function and speed of processing. Cholinesterase inhibitors have cognitive enhancing effects in vascular dementia, but the major thrust is still aggressive management of vascular risk factors and healthy lifestyle choices. Given that mixed Alzheimer's dementia and CVD is likely the most common substrate for dementia and that they share common vascular risk factors, a major goal for vascular medicine is cerebrovascular protection, not just to prevent heart attack and stroke, but also to maintain brain health and delay dementia. © sandra.black@sunnybrook.ca.",,"Black, S. E.",2011,2011,,0,
5331,Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment,"Most strokes are covert and observed incidentally on brain scans, but their presence increases risk of overt stroke and dementia. Amyloid angiopathy, associated with Alzheimer Disease (AD) causes stroke, and when even small strokes coexist with AD, they lower the threshold for dementia. Diffuse ischemic white matter disease impairs executive functioning, information processing speed, and gait. Neuroimaging techniques, such as tissue segmentation, Diffusion Tensor Imaging, MR Spectroscopy, functional MRI and amyloid PET, probe microstructural integrity, molecular biology, and activation patterns, providing new insights into brain-behavior relationships. MR-pathological studies of periventricular hyperintensity (leukoaraiosis) in aging and dementia reveal arteriolar tortuosity, reduced vessel density, and occlusive venous collagenosis which causes venous insufficiency and vasogenic edema. Activated microglia, oligodendroglial apoptosis, clasmatodendritic astrocytosis, and upregulated hypoxia-markers are seen on immunohistochemistry. Further research is needed to understand and treat this chronic subcortical vascular disease, which is epidemic in our aging population.","Aging/ pathology;Alzheimer Disease/pathology;Cognition Disorders/ pathology;Dementia, Vascular/ pathology;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Positron-Emission Tomography","Black, S.;Gao, F.;Bilbao, J.",2009,Mar,10.1161/strokeaha.108.537704,0,
5332,Pentoxifylline in cerebrovascular dementia,"Objective: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. Design: Randomized, double-blind, placebo-controlled, parallel group trial. Setting: Outpatient tertiary care center. Patients: 64 patients meeting DSM- III criteria for multi-infarct dementia with modified Hachinski ischemic scores ≥6, 38 of whom completed the trial. Intervention: Pentoxifylline (Trental®) 400 milligram tablets three times daily vs placebo for 36 weeks. Main Outcome Measure: Alzheimer's Disease Assessment Scale (ADAS). Results: Baseline demographic values and psychometric variables were similar in the placebo and control groups; end-point statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. Conclusion: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for 'multi-infarct dementia' and who also have clinical and neuroradiological evidence of cerebrovascular disease.",pentoxifylline;adult;aged;Alzheimer disease;article;cerebrovascular disease;clinical article;controlled study;dementia;female;human;intermittent claudication;male;multiinfarct dementia;oral drug administration;outpatient;priority journal;trental,"Black, R. S.;Barclay, L. L.;Nolan, K. A.;Thaler, H. T.;Hardiman, S. T.;Blass, J. P.",1992,,,0,
5333,Pentoxifylline in cerebrovascular dementia,"OBJECTIVE: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial. SETTING: Outpatient tertiary care center. PATIENTS: 64 patients meeting DSM-III criteria for multi-infarct dementia with modified Hachinski ischemic scores greater than or equal to 6, 38 of whom completed the trial. INTERVENTION: Pentoxifylline (Trental) 400 milligram tablets three times daily vs placebo for 36 weeks. MAIN OUTCOME MEASURE: Alzheimer's Disease Assessment Scale (ADAS). RESULTS: Baseline demographic values and psychometric variables were similar in the placebo and control groups; endpoint statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. CONCLUSION: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for ""multi-infarct dementia"" and who also have clinical and neuroradiological evidence of cerebrovascular disease.","Academic Medical Centers;Administration, Oral;Cognition;Dementia, Multi-Infarct [diagnosis] [drug therapy] [etiology];Double-Blind Method;Magnetic Resonance Imaging;Neuropsychological Tests;New York;Outpatient Clinics, Hospital;Pentoxifylline [administration & dosage] [pharmacology] [therapeutic use];Rehabilitation Centers;Severity of Illness Index;Tomography, X-Ray Computed;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia: sr-stroke","Black, R. S.;Barclay, L. L.;Nolan, K. A.;Thaler, H. T.;Hardiman, S. T.;Blass, J. P.",1992,,,0,5332
5334,Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy,"BACKGROUND: Small vessel disease (SVD) represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF) biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD. METHODS: CSF SVD-related biomarkers [neurofilament light (NF-L), myelin basic protein (MBP), soluble amyloid precursor protein-beta (sAPPbeta), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMP)] were analysed in 46 non-demented elderly with imaging findings of SVD. We assessed the relationship between the CSF biomarkers and white matter hyperintensity (WMH) volume, diffusion-weighted imaging and atrophy as well as their association with neuropsychological profiles. RESULTS: The WMH volume correlated with ventricular dilation, which was associated with executive function and speed and attention. Increased WMH and ventricular dilation were related to increased CSF levels of TIMP-1, NF-L and MBP and to decreased sAPPbeta. A positive correlation was found between the CSF biomarker MMP-9 and WMH progression. CONCLUSIONS: The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration. CSF TIMP-1, NF-L, MBP and sAPPbeta may function as biological markers of white matter damage.",,"Bjerke, M.;Jonsson, M.;Nordlund, A.;Eckerstrom, C.;Blennow, K.;Zetterberg, H.;Pantoni, L.;Inzitari, D.;Schmidt, R.;Wallin, A.",2014,Sep,10.1159/000366119,0,
5335,Improvements in a Mouse Model of Alzheimer's Disease Through SOD2 Overexpression are Due to Functional and Not Structural Alterations,"Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease. We and others have shown that over expression of the mitochondrial antioxidant superoxide dismutase 2 (SOD-2) can improve many of the pathologies in the Tg2576 mouse model of Alzheimer's disease that harbors the Swedish mutation in the amyloid precursor protein. However, it is not clear if these improvements are due to functional improvements or structural/anatomical changes. To answer this question, we used diffusion tensor imaging (DTI) to assess the structural integrity of white matter tracts in the control mice, Tg2576 mouse and Tg2576 mice over expressing SOD-2. We observed minimal differences in diffusion parameters with SOD-2 over expression in this model indicating that the improvements we previously reported are due to functional changes and not any alterations to the white matter tractography.",,"Bitner, B. R.;Perez-Torres, C. J.;Hu, L.;Inoue, T.;Pautler, R. G.",2012,Mar 29,10.4137/mri.s9352,0,
5336,"Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder-a systematic review of the magnetic resonance neuroimaging literature","Since Emil Kraepelin's conceptualization of endogenous psychoses as dementia praecox and manic depression, the separation between primary psychotic disorders and primary affective disorders has been much debated. We conducted a systematic review of case-control studies contrasting magnetic resonance imaging studies in schizophrenia and bipolar disorder. A literature search in PubMed of studies published between January 2005 and December 2016 was conducted, and 50 structural, 29 functional, 7 magnetic resonance spectroscopy, and 8 combined imaging and genetic studies were deemed eligible for systematic review. Structural neuroimaging studies suggest white matter integrity deficits that are consistent across the illnesses, while gray matter reductions appear more widespread in schizophrenia compared to bipolar disorder. Spectroscopy studies in cortical gray matter report evidence of decreased neuronal integrity in both disorders. Functional neuroimaging studies typically report similar functional architecture of brain networks in healthy controls and patients across the psychosis spectrum, but find differential extent of alterations in task related activation and resting state connectivity between illnesses. The very limited imaging-genetic literature suggests a relationship between psychosis risk genes and brain structure, and possible gene by diagnosis interaction effects on functional imaging markers. While the existing literature suggests some shared and some distinct neural markers in schizophrenia and bipolar disorder, it will be imperative to conduct large, well designed, multi-modal neuroimaging studies in medication-naive first episode patients that will be followed longitudinally over the course of their illness in an effort to advance our understanding of disease mechanisms.",,"Birur, B.;Kraguljac, N. V.;Shelton, R. C.;Lahti, A. C.",2017,,,0,
5337,Abdominal obesity and white matter microstructure in midlife,"The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40-62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization, and tract-based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.",Mri;adiposity;aging;diffusion tensor imaging;waist circumference,"Birdsill, A. C.;Oleson, S.;Kaur, S.;Pasha, E.;Ireton, A.;Tanaka, H.;Haley, A.",2017,Apr 8,,0,
5338,"Regional white matter hyperintensities: aging, Alzheimer's disease risk, and cognitive function","White matter hyperintensities (WMH) of presumed vascular origin, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging, are known to increase with age and are elevated in Alzheimer's disease (AD). The cognitive implications of these common markers are not well understood. Previous research has primarily focused on global measures of WMH burden and broad localizations that contain multiple white matter tracts. The aims of this study were to determine the pattern of WMH accumulation with age, risk for AD, and the relationship with cognitive function utilizing a voxel-wise analysis capable of identifying specific white matter regions. A total of 349 participants underwent T1-weighted and high-resolution T2-weighted fluid attenuated inversion recovery magnetic resonance imaging and neuropsychological testing. Increasing age and lower cognitive speed and flexibility (a component of executive function), were both significantly associated with regional WMH throughout the brain. When age was controlled, lower cognitive speed and flexibility was independently associated with WMH in the superior corona radiata. Apolipoprotein E epsilon4 and parental family history of AD were not associated with higher burden of WMH. The results contribute to a larger body of literature suggesting that white matter measures are linked with processing speed, and illustrate the utility of voxel-wise analysis in understanding the effect of lesion location on cognitive function.",Adult;Aged;Aging/ pathology;Alzheimer Disease/diagnosis/ pathology/ psychology;Apolipoprotein E4;Brain/ pathology;Cognition;Diffusion Magnetic Resonance Imaging;Female;Humans;Male;Middle Aged;Neuropsychological Tests;Risk,"Birdsill, A. C.;Koscik, R. L.;Jonaitis, E. M.;Johnson, S. C.;Okonkwo, O. C.;Hermann, B. P.;Larue, A.;Sager, M. A.;Bendlin, B. B.",2014,Apr,10.1016/j.neurobiolaging.2013.10.072,0,
5339,Low cerebral blood flow is associated with lower memory function in metabolic syndrome,"BACKGROUND: Metabolic syndrome (MetS)--a cluster of cardiovascular risk factors--is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed. DESIGN AND METHODS: Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. RESULTS: Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF. CONCLUSIONS: The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population.","Age Factors;Aged;Alzheimer Disease/etiology/physiopathology;Apolipoprotein E4/metabolism;Blood Glucose/metabolism;Blood Pressure;Brain/anatomy & histology;Cerebrovascular Circulation/ physiology;Cholesterol, HDL/blood;Cognition Disorders/etiology/ physiopathology;Cross-Sectional Studies;Fasting;Female;Humans;Magnetic Resonance Imaging;Male;Memory/ physiology;Metabolic Syndrome X/complications/ physiopathology;Middle Aged;Neuropsychological Tests;Organ Size;Regional Blood Flow;Risk Factors;Spin Labels;Triglycerides/blood;Wisconsin","Birdsill, A. C.;Carlsson, C. M.;Willette, A. A.;Okonkwo, O. C.;Johnson, S. C.;Xu, G.;Oh, J. M.;Gallagher, C. L.;Koscik, R. L.;Jonaitis, E. M.;Hermann, B. P.;LaRue, A.;Rowley, H. A.;Asthana, S.;Sager, M. A.;Bendlin, B. B.",2013,Jul,10.1002/oby.20170,0,
5340,"Clinical, radiological, histopathological and genetic findings in a Danish ""CADASIL"" family","Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare adult-onset inherited arterial disease with a distinctive neuropathological phenotype. Owing to its recent identification and variable mode of presentation, the disease is often misdiagnosed. The CADASIL gene is Notch 3 and has been mapped on chromosome 19q12 in several unrelated families. Knowledge of the phenotypic range of CADASIL, however, remains incomplete. Clinical, pathological radiological, and genetic findings in the first known Danish CADASIL pedigree are presented. Genetic testing confirmed a Notch 3 mutation. The mutation consisted of the substitution of a nucleotide at position 475 leading to the replacement of amino acid arginine for cysteine at position 133 in the third EGF motif.",adult;article;autosome;basement membrane;brain;case report;Denmark;female;genetic procedures;genetics;human;male;middle aged;multiinfarct dementia;mutation;nuclear magnetic resonance imaging;pathology;pedigree;phenotype;radiography;ultrastructure,"Binzer, M. N.;Brattström, L.;Ottosen, P.;Videbaek, H.;Stenager, E.",2000,,,0,
5341,Delusions and dementia: clinical and CT correlates,"INTRODUCTION: Delusions occur frequently during the course of Alzheimer's disease (AD) and multi-infarct dementia (MID). Their clinical significance and their relationship with progression of disease and involvement of selected cerebral areas are still unclear. The aim of the study was to determine the clinical and CT correlates of delusions in patients with dementia. MATERIAL AND METHODS: A series of 67 probable AD and 32 MID patients, underwent computed tomographic scans, psychometric tests, neurologic and psychiatric examination, and blood and serum tests. RESULTS: Twenty-four patients were found to have delusions during the clinical evaluation. Delusional patients showed a significantly higher age when compared with non-delusional patients. The results of a multiple logistic regression (with stepwise deletion of the redundant variables) of the CT lesions on the presence of delusions, showed that only the presence of isolated white matter lesions in the frontal lobes were significantly related to the occurrence of delusions (Exp B = 3.42; Beta = 1.2; S.E. = 0.6; Sig T = 0.04). Frontal white matter changes were significantly related to delusions when a multiple regression analysis, entering age and total number of lesions at CT scans, was carried out. CONCLUSIONS: We found that focal lesions in the frontal areas were the only variable that appeared to be significantly and independently associated with delusional disorders.","Activities of Daily Living/psychology;Aged;Aged, 80 and over;Alzheimer Disease/psychology/*radiography;Brain/*radiography;Delusions/psychology/*radiography;Dementia, Multi-Infarct/psychology/*radiography;Female;Frontal Lobe/radiography;Geriatric Assessment;Humans;Male;Mental Status Schedule;*Tomography, X-Ray Computed","Binetti, G.;Padovani, A.;Magni, E.;Bianchetti, A.;Scuratti, A.;Lenzi, G. L.;Trabucchi, M.",1995,Apr,,0,
5342,The relationship of white matter hyperintensities with depressive symptoms and daily living activities in early-stage Alzheimer's disease patients,"Introduction: Cerebral white matter hyperintensities (WMHs) detected on magnetic resonance imaging scans are frequently seen in both Alzheimer's disease (AD) and depression patients and believed to play an important role in cognition and mood. Depressive symptoms and depression may accompany AD in all stages of the disease. The aim of the study was to evaluate the relationship of regional WMHs with depressive symptoms, cognitive status, medial temporal lobe atrophy, and daily living activities in early-stage AD patients. Methods: Forty-five patients with very mild or mild AD were examined. All subjects underwent MRI and were assessed by the Geriatric Depression Scale (GDS) and the Addenbrooke's Cognitive Examination-Revised (ACE-R) for the evaluation of depressive symptom severity and cognitive status, respectively. The patients were divided into two groups based on the selected cut-off point in the GDS. CDR sum of the boxes (CDR-sb) scores were calculated as a measure of activities of daily living (ADLs). MRI T2-FLAIR slices were used to rate the white-matter lesions according to the Age-Related White Matter Changes Rating Scale, assessing the WMHs in frontal, parietooccipital, temporal, infratentorial and basal ganglia areas individually. Medial temporal lobe atrophy was assessed with high-resolution T1 images using visual rating scale. Results: In the depressive group, frontal WMH scores were found to be higher than in the non-depressive group (p=0.006). ACE-r, CDR-sb and medial temporal lobe atrophy scores did not differ among the groups. CDR-sb scores showed a significant correlation with frontal WMH scores (left frontal WMH r=0.439, p=0.003, right frontal AMH r=0.459, p=0.001). Linear regression models revealed the effect of WMHs on depressive symptoms among the other factors including age, functionality and atrophy in the medial temporal areas. Discussion: Our findings underscore the potential role of regional, particularly frontal AMHs in depressive symptoms and functionality of the early AD patients. © Archives of Neuropsychiatry, published by Galenos Publishing.",,"Bilgiç, B.;Bayram, A.;Hanaǧasi, H. A.;Tümaç, A.;Uysal, P.;Şentürk, G.;Alpsan, H.;Lohmann, E.;Gürvit, H.;Emre, M.",2013,2013,,0,
5343,Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease,"BACKGROUND: Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. OBJECTIVE: To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. METHODS: Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. RESULTS: CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. CONCLUSION: Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.",,"Bilello, M.;Doshi, J.;Nabavizadeh, S. A.;Toledo, J. B.;Erus, G.;Xie, S. X.;Trojanowski, J. Q.;Han, X.;Davatzikos, C.",2015,,10.3233/jad-150400,0,
5344,"White matter lesions, quantitative magnetic resonance imaging, and dementia","The authors performed quantitative and qualitative image analysis on a sample of the elderly population of Cache County, Utah, relating neuroimaging findings to Mini-Mental Status Examination (MMSE) scores and the presence of the apolipoprotein E epsilon4 allele. Neuroimaging measures included white, gray, and hippocampal volumes; a ventricle-to-brain ratio (VBR); and qualitative ratings of white matter lesions (WMLs) in the periventricular (PV) and centrum semiovale (CS) regions. Subjects included 85 persons with possible and probable Alzheimer disease (AD), 21 with vascular dementia (VaD), 30 with cognitive symptoms classified as mild/ambiguous (M/A), a heterogenous group of 39 non-AD or VaD subjects but diagnosed with some form of neuropsychiatric disorder (""Mixed Neuropsychiatric"" group), and 20 normal control subjects aged 65 years or older. Controlling for age, sex, and length of disease, the authors found that AD and VaD subjects differed significantly from control subjects on WMLs, but only the VaD subjects significantly differed from M/A subjects. The two dementia groups also displayed, as expected, significant cerebral atrophy. The WMLs generally increased with age and severity of dementia. PV WMLs were significantly but only modestly associated with white matter volume loss and greater impairment on the MMSE. Modest correlations were also present between the quantitative measures of cerebral structure and MMSE performance. However, when degree of cerebral atrophy was controlled by using the VBR measure, WML effects on MMSE performance became nonsignificant, with the only significant relationship remaining being that between hippocampal volume and MMSE performance. There were no significant qualitative or quantitative findings related to presence of the epsilon4 allele and MMSE performance. The role of WMLs in aging and dementia is discussed.","Aged;Alleles;Alzheimer Disease/ diagnosis/genetics;Apolipoprotein E4;Apolipoproteins E/genetics;Atrophy;Brain/ pathology;Female;Hippocampus/pathology;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Reference Values","Bigler, E. D.;Kerr, B.;Victoroff, J.;Tate, D. F.;Breitner, J. C.",2002,Jul-Sep,,0,
5345,"Role of white matter lesions, cerebral atrophy, and APOE on cognition in older persons with and without dementia: The Cache County, Utah, study of memory and aging","Neuropsychological, qualitative, and quantitative magnetic resonance imaging findings were examined in subjects with Alzheimer's disease (AD), non-AD dementia or mixed neuropsychiatric disorder, subjects characterized as mild/ambiguous, and controls, all with known apolipoprotein E (APOE) genotype. Neuropsychological tasks included an expanded Consortium to Establish a Registery for Alzheimer's Disease (J. T. Tschanz et al., 2000; K. A. Welsh, J. M. Hoffman, N. L. Earl, & M. W. Hanson 1994) battery and the Mini-Mental Status Examination (M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975). Periventricular white matter lesions were the most clinically salient, and generalized measures of cerebral atrophy were the most significant quantitative indicators. APOE genotype was unrelated to imaging or neuropsychological performance. Neuropsychological relationships with neuroimaging findings depend on the qualitative or quantitative method used.",,"Bigler, E. D.;Kerr, B.;Tate, D. F.;Hessel, C. D.;Earl, H. D.;Miller, M. J.;Rice, S. A.;Smith, K. H.;Welsh-Bohmer, K.;Plassman, B.;Lowry, C. M.;Tschanz, J. T.;Victoroff, J.",2003,July,,0,
5346,Delayed seizures after intracerebral haemorrhage,"Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants epsilon2/epsilon4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of >/= 1 APOE epsilon4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.",epilepsy;intracerebral haemorrhage;seizure,"Biffi, A.;Rattani, A.;Anderson, C. D.;Ayres, A. M.;Gurol, E. M.;Greenberg, S. M.;Rosand, J.;Viswanathan, A.",2016,Oct,,0,5347
5347,Delayed seizures after intracerebral haemorrhage,"Late seizures after intracerebral haemorrhage occur after the initial acute haemorrhagic insult subsides, and represent one of its most feared long-term sequelae. Both susceptibility to late seizures and their functional impact remain poorly characterized. We sought to: (i) compare patients with new-onset late seizures (i.e. delayed seizures), with those who experienced a recurrent late seizure following an immediately post-haemorrhagic seizure; and (ii) investigate the effect of late seizures on long-term functional performance after intracerebral haemorrhage. We performed prospective longitudinal follow-up of consecutive intracerebral haemorrhage survivors presenting to a single tertiary care centre. We tested for association with seizures the following neuroimaging and genetic markers of cerebral small vessel disease: APOE variants epsilon2/epsilon4, computer tomography-defined white matter disease, magnetic resonance imaging-defined white matter hyperintensities volume and cerebral microbleeds. Cognitive performance was measured using the Modified Telephone Interview for Cognitive Status, and functional performance using structured questionnaires obtained every 6 months. We performed time-to-event analysis using separate Cox models for risk to develop delayed and recurrent seizures, as well as for functional decline risk (mortality, incident dementia, and loss of functional independence) after intracerebral haemorrhage. A total of 872 survivors of intracerebral haemorrhage were enrolled and followed for a median of 3.9 years. Early seizure developed in 86 patients, 42 of whom went on to experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma volume and cortical involvement were associated with recurrent seizure risk (all P < 0.01). Recurrent seizures were not associated with long-term functional outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors associated with delayed seizures included cortical involvement on index haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P = 0.008) and presence of >/= 1 APOE epsilon4 copies (hazard ratio 1.95, P = 0.020). Delayed seizures were associated with worse long-term functional outcome (hazard ratio 1.83, P = 0.005), but the association was removed by adjusting for neuroimaging and genetic markers of cerebral small vessel disease. Delayed seizures after intracerebral haemorrhage are associated with different risk factors, when compared to recurrent seizures. They are also associated with worse functional outcome, but this finding appears to be related to underlying small vessel disease. Further investigations into the connections between small vessel disease and delayed seizures are warranted.",epilepsy;intracerebral haemorrhage;seizure,"Biffi, A.;Rattani, A.;Anderson, C. D.;Ayres, A. M.;Gurol, E. M.;Greenberg, S. M.;Rosand, J.;Viswanathan, A.",2016,Aug 6,10.1093/brain/aww199,0,
5348,Risk Factors Associated With Early vs Delayed Dementia After Intracerebral Hemorrhage,"IMPORTANCE: Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term. OBJECTIVE: To identify and compare risk factors for early and delayed dementia after ICH. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID). EXPOSURES: Intracerebral hemorrhage. MAIN OUTCOMES AND MEASURES: Cognitive performance was captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH. RESULTS: Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID. CONCLUSIONS AND RELEVANCE: Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.",,"Biffi, A.;Bailey, D.;Anderson, C. D.;Ayres, A. M.;Gurol, E. M.;Greenberg, S. M.;Rosand, J.;Viswanathan, A.",2016,Aug 1,10.1001/jamaneurol.2016.0955,0,
5349,Genetic variation and neuroimaging measures in Alzheimer disease,"OBJECTIVE: To investigate whether genome-wide association study (GWAS)-validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status. DESIGN: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative. SETTING: Multicenter GWAS. Patients A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available. MAIN OUTCOME MEASURES: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness. RESULTS: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate-corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score-based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05). CONCLUSIONS: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.","Adaptor Proteins, Signal Transducing/ genetics;Aged;Aged, 80 and over;Alzheimer Disease/ genetics/ pathology;Apolipoproteins E/ genetics;Canada;Cell Adhesion Molecules, Neuronal/genetics;Cognition Disorders/genetics/pathology;Female;Genetic Predisposition to Disease;Genome-Wide Association Study;Genotype;Humans;Image Interpretation, Computer-Assisted;Logistic Models;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests;Nuclear Proteins/ genetics;Odds Ratio;Polymorphism, Single Nucleotide/ genetics;Reproducibility of Results;Risk Factors;Tumor Suppressor Proteins/ genetics;United States","Biffi, A.;Anderson, C. D.;Desikan, R. S.;Sabuncu, M.;Cortellini, L.;Schmansky, N.;Salat, D.;Rosand, J.",2010,Jun,10.1001/archneurol.2010.108,0,
5350,Diabetes and cognitive impairment. Clinical diagnosis and brain imaging in patients attending a memory clinic,"BACKGROUND: Diabetes is a risk factor for dementia,but the issue whether this concerns only vascular dementia or also Alzheimer's disease is debated. We compared the clinical diagnoses and abnormalities on brain MRI in patients with or without diabetes who received standardised, detailed diagnostic studies at a memory clinic, in order to establish whether one specific type of dementia or specific MRI abnormalities were more common in diabetes. PATIENTS AND METHODS: Patients who visited our memory clinic between January 2002 and June 2004 were divided into a group with (n = 42) or without diabetes (n = 389). The diagnoses were recorded, and MRI scans were rated for (sub)cortical atrophy, medial temporal lobe atrophy, infarctions, and white matter changes. RESULTS: The proportion of Alzheimer's disease (36% versus 28%; OR 1.1 (95% CI 0.5-2.2), adjusted for age and sex), vascular dementia (5% versus 2%; OR 2.4 (0.5-12.1)), and so called ""cognitive impairment no dementia"" (24% versus 17%; 1.3 (0.6-2.9)) was similar in patients with or without diabetes. On MRI lacunar and cortical infarctions were more common and cortical atrophy more pronounced among diabetic patients. By contrast, the severity of white matter changes was similar in the two groups. CONCLUSION: The relative frequency of different diagnoses among diabetic and non-diabetic patients attending a memory clinic was similar, indicating that diabetes does not predispose to one particular subtype of dementia. The imaging findings support the notion that the increased risk of cognitive decline and dementia in elderly subjects with diabetes is due to dual pathology, involving both cerebrovascular disease and cortical atrophy.","Aged;Atrophy;Blood Glucose/metabolism;Brain/pathology;Cognition Disorders/ diagnosis/epidemiology/ psychology;Dementia/epidemiology/etiology/psychology;Diabetes Complications/ diagnosis/epidemiology/ psychology;Diabetes Mellitus/ psychology;Diabetic Angiopathies/epidemiology/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Memory Disorders/ diagnosis/epidemiology/ psychology;Neuropsychological Tests;Tomography, X-Ray Computed","Biessels, G. J.;Koffeman, A.;Scheltens, P.",2006,Apr,10.1007/s00415-005-0036-4,0,
5351,Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus,"Background: The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. Objective: To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. Methods: In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. Results: The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non-DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. Conclusion: The results suggest that non-vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2.",,"Biessels, G. J.;De Leeuw, F. E.;Lindeboom, J.;Barkhof, F.;Scheltens, P.",2006,March,,0,
5352,Diagnosis and treatment of vascular damage in dementia,"This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called ""silent vascular damage,"" without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock.",,"Biessels, G. J.",2016,May,10.1016/j.bbadis.2015.11.009,0,
5353,Microstructure of Strategic White Matter Tracts and Cognition in Memory Clinic Patients with Vascular Brain Injury,"BACKGROUND: White matter injury is an important factor for cognitive impairment in memory clinic patients. We determined the added value of diffusion tensor imaging (DTI) of strategic white matter tracts in explaining variance in cognition in memory clinic patients with vascular brain injury. METHODS: We included 159 patients. Conventional MRI markers (white matter hyperintensity volume, lacunes, nonlacunar infarcts, brain atrophy, and microbleeds), and fractional anisotropy and mean diffusivity (MD) of the whole brain white matter and of 18 white matter tracts were related to cognition using linear regression and Bayesian network analysis. RESULTS: On top of all conventional MRI markers combined, MD of the whole brain white matter explained an additional 3.4% (p = 0.014), 7.8% (p < 0.001), and 1.2% (p = 0.119) variance in executive functioning, speed, and memory, respectively. The Bayesian analyses of regional DTI measures identified strategic tracts for executive functioning (right superior longitudinal fasciculus), speed (left corticospinal tract), and memory (left uncinate fasciculus). MD within these tracts explained an additional 3.4% (p = 0.012), 3.8% (p = 0.007), and 2.1% (p = 0.041) variance in executive functioning, speed, and memory, respectively, on top of all conventional MRI and global DTI markers combined. CONCLUSION: In memory clinic patients with vascular brain injury, DTI of strategic white matter tracts has a significant added value in explaining variance in cognitive functioning.",Alzheimer disease;Diffusion tensor imaging;Small vessel disease;Strategic white matter tract;Vascular dementia,"Biesbroek, J. M.;Leemans, A.;den Bakker, H.;Duering, M.;Gesierich, B.;Koek, H. L.;van den Berg, E.;Postma, A.;Biessels, G. J.;on behalf of the Utrecht Vascular Cognitive Impairment study, group",2018,Jan 19,,0,
5354,The impact of intracranial artery disease and prior cerebral infarction on central nervous system complications after off-pump coronary artery bypass grafting,"Background: Improvements in off-pump coronary artery bypass grafting (OPCABG) have focused interest on neurological injuries, such as stroke and cognitive decline, which may accompany an otherwise successful operation. The purpose of this study was to determine whether postoperative central nervous system (CNS) complications was related to prior cerebral infarction demonstrated by magnetic resonance imaging (MRI) or intracranial artery disease demonstrated by magnetic resonance angiography (MRA). Methods: The study sample comprised 55 consecutive patients (40 men; mean age, 64.59±8.86 years) who underwent OPCABG. Each patient underwent neurological and neuropsychological examinations 24 hours before surgery. MRI was used to identify old and/or new ischemic lesions before surgery and MRA was used to determine the presence and severity of intracranial artery disease. Patients were followed 8 days after surgery and evaluated for the development of stroke or cognitive dysfunction. Associations between postoperative stroke and potential predictors, including prior cerebral infarction and intracranial artery disease, were analyzed using univariate methods. Results: Two of 55 (3.64%) patients had postoperative stroke and no patient showed cognitive decline. Univariate analysis found no association between postoperative stroke and prior cerebral infarction detected by MRI (P=0.378) or intracranial artery disease detected by MRA (P=0.103). Conclusion: Our results suggest that intracranial artery disease and prior cerebral infarction detected on MRI are not independent risk factors for stroke after OPCABG. However, given the small sample of patients included in this study, further investigation of these associations is necessary.",,"Bi, Q.;Jun-Yu, L.;Xiao-Qing, L.;Qin, L.;Di, L.;Qiu-Bo, Q.",2014,2014,,0,
5355,Ekbom syndrome occurring with multi infarct dementia,Ekbom Syndrome is characterized by delusion that small living being infests skin. The clinical profile of this disorder has shown it to be associated with organic conditions. Neuroimaging studies implicate putamen as the brain structure involved in the pathophysiology. These are also known as organic delusional disorder and provide an opportunity to study biological causation of delusional disorder. We report a patient presented with a complaint of insects crawling on her body for last two years. She collected the peeled skin in a jar and claimed that these are insects. CT scan (brain) revealed multiple infarcts involving basal ganglia. She responded to Risperidone 4 mg daily.,Atypical antipsychotics;Delusional parasitosis;Organicity,"Bhatia, M. S.;Gautam, P.;Kaur, J.",2015,Apr,10.7860/jcdr/2015/12584.5851,0,
5356,A Multimodal Structural and Functional Neuroimaging Study of Amnestic Mild Cognitive Impairment,"Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia.",Alzheimer's disease;dementia;diffusion tensor imaging (DTI);functional magnetic resonance imaging (fMRI);independent component analysis (ICA);tract-based spatial statistics (TBSS),"Bharath, S.;Joshi, H.;John, J. P.;Balachandar, R.;Sadanand, S.;Saini, J.;Kumar, K. J.;Varghese, M.",2017,Feb,,0,5357
5357,A Multimodal Structural and Functional Neuroimaging Study of Amnestic Mild Cognitive Impairment,"Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia.",Alzheimer's disease;dementia;diffusion tensor imaging (DTI);functional magnetic resonance imaging (fMRI);independent component analysis (ICA);tract-based spatial statistics (TBSS),"Bharath, S.;Joshi, H.;John, J. P.;Balachandar, R.;Sadanand, S.;Saini, J.;Kumar, K. J.;Varghese, M.",2016,May 4,10.1016/j.jagp.2016.05.001,0,
5358,Visual rating of white matter hyperintensities in Parkinson's disease,"Dementia is a common complication of Parkinson's disease (PD), but the cause is incompletely understood. In previous studies, dementia has been associated with an increase in hyperintense lesions in the cerebral white matter. The aim of this study was to explore whether white matter hyperintensities (WMH) on cerebral magnetic resonance imaging (MRI) are associated with dementia in PD. For this study, 35 patients with PD, 16 with dementia (PDD) and 19 without (PDND), and 20 control subjects were recruited. MRI scans of patients and controls were rated for WMH, blind to diagnosis, using the Scheltens visual rating scale. Both bivariate and multivariate statistical analyses were carried out. Cerebrovascular risk factors, education, gender, or age were similar across groups. Compared with the PDND group, the PDD group had significantly higher level of WMH in the deep white matter and in the periventricular areas. WMH in the deep white matter was the only variable that was associated significantly with Mini-Mental State Examination score and explained 38% of the variance in the multivariate linear regression analysis. Our findings suggest that WMH in the deep white matter may contribute to dementia in PD.","Aged;Brain/ pathology;Cerebral Ventricles/pathology;Cognition Disorders/diagnosis;Dementia/ diagnosis;Dementia, Vascular/diagnosis;Female;Frontal Lobe/pathology;Humans;Male;Mental Status Schedule;Neurologic Examination;Observer Variation;Parkinson Disease/ diagnosis;Reference Values;Risk Factors","Beyer, M. K.;Aarsland, D.;Greve, O. J.;Larsen, J. P.",2006,Feb,10.1002/mds.20704,0,
5359,"Presentation of bilateral thalamic infarction on CT, MRI and PET","Paramedian thalamic structures and part of the upper midbrain are frequently supplied by posterior thalamoperforating arteries originating from one common trunk. Local impairment of flow entails a bilateral more or less symmetric thalamiuc infarction with varying involvement of the midbrain. Diagnosis usually can neither be firmly established on clinical grounds nor by angiography alone. In the present series of four patients the two cases observed before the CT era were diagnosed correctly only at autopsy. Only one patient presented the classical syndrome of hypersomnia, thalamic dementia, and oculomotor nerve paralysis, while in the others clinical signs were probably masked by serious impairment of consciousness. In two cases X-ray computed tomography and magnetic resonance tomography (one case) afforded precise definition of infarct localization and size. Infarction in the described terminal vascular supply territory may be detected more often by these modern diagnostic techniques than anticipated from previous clinico-pathological experience as the underlying cause of coma in the elderly - a group of patients at particular risk for low-flow states. Positron emission tomography repeat studies with 18F-2-fluorodeoxyglucose (one case) revealed complex disturbances of brain energy metabolism; correlative analysis of clinical function and metabolic patterns during the course of the disease may not only advance individual prognostication but also contribute to the understanding and localization of brain function.",fluorodeoxyglucose f 18;radioisotope;adult;aged;case report;central nervous system;computer analysis;computer assisted tomography;diagnosis;human;human experiment;infarction;nuclear magnetic resonance imaging;peripheral vascular system;positron emission tomography;priority journal;thalamus,"Bewermeyer, H.;Dreesbach, H. A.;Rackl, A.",1985,,,0,
5360,High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7 T,"Quantitative susceptibility mapping (QSM) has recently emerged as a novel magnetic resonance imaging (MRI) method to detect non-haem iron deposition, calcifications, demyelination and vascular lesions in the brain. It has been suggested that QSM is more sensitive than the more conventional quantifiable MRI measure, namely the transverse relaxation rate, R2*. Here, we conducted the first high-resolution, whole-brain, simultaneously acquired, comparative study of the two techniques using 7 Tesla MRI. We asked which of the two techniques would be more sensitive to explore global differences in tissue composition in elderly adults relative to young subjects. Both QSM and R2* revealed strong age-related differences in subcortical regions, hippocampus and cortical grey matter, particularly in superior frontal regions, motor/premotor cortices, insula and cerebellar regions. Within the basal ganglia system—but also hippocampus and cerebellar dentate nucleus—, QSM was largely in agreement with R2* with the exception of the globus pallidus. QSM, however, provided superior anatomical contrast and revealed age-related differences in the thalamus and in white matter, which were otherwise largely undetected by R2* measurements. In contrast, in occipital cortex, age-related differences were much greater with R2* compared to QSM. The present study, therefore, demonstrated that in vivo QSM using ultra-high field MRI provides a novel means to characterise age-related differences in the human brain, but also combining QSM and R2* using multi-gradient recalled echo imaging can potentially provide a more complete picture of mineralisation, demyelination and/or vascular alterations in aging and disease.",adult;age distribution;aged;aging;anatomic landmark;article;basal ganglion;brain aging;brain mapping;cerebellum;comparative study;controlled study;data extraction;dentate nucleus;effect size;female;globus pallidus;gray matter;hippocampus;human;image analysis;image reconstruction;imaging;in vivo study;insula;male;middle aged;morphology;multi gradient recalled echo imaging;neuroanatomy;neuroimaging;normal human;nuclear magnetic resonance imaging;occipital cortex;premotor cortex;priority journal;quantitative susceptibility mapping;radiological parameters;sensitivity analysis;subcortex;substantia nigra;subthalamic nucleus;superior frontal gyrus;test retest reliability;thalamus;tissue composition;transverse relaxation rate;validation process;white matter,"Betts, M. J.;Acosta-Cabronero, J.;Cardenas-Blanco, A.;Nestor, P. J.;Düzel, E.",2016,,,0,
5361,In Vivo Comparison of Tau Radioligands (18)F-THK-5351 and (18)F-THK-5317,"This study compared the in vivo imaging characteristics of tau PET ligands (18)F-THK-5351 and (18)F-THK-5317 in the context of Alzheimer disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and SUV ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification. Methods: Twenty-eight subjects (mean age +/- SD, 71 +/- 7 y) underwent either dynamic 90-min (18)F-THK-5317 or (18)F-THK-5351 PET scans. Bland-Altman plots were used to compare the simplified reference tissue method, multilinear reference tissue method (MRTM2), and Logan reference tissue DVR estimates and to assess temporal stability of SUVR windows using cerebellar gray matter as a reference region. In vivo kinetics and DVR estimates were directly compared for 10 subjects who underwent both (18)F-THK-5317 and (18)F-THK-5351 PET scans. Results: THK-5351 exhibited faster cerebellar gray matter clearance, faster cortical white matter clearance, and higher DVR estimates in AD tau-associated regions of interest than THK-5317. The MRTM2 method produced the most reliable DVR estimates for both tracers, particularly when scan duration was shortened to 60 min. SUVR stability was observed 50-70 min after injection for both tracers. Parametric images revealed differences between MRTM2, Logan, and SUVR binding in white matter regions for THK-5317. Conclusion: THK-5317 and THK-5351 show promise for in vivo detection of AD tau. THK-5351 has more favorable pharmacokinetics and imaging characteristics than THK-5317.","0 (6-((3-fluoro-2-hydroxy)propoxy)-2-(4-methylaminophenyl)quinoline);0 (Aminopyridines);0 (Aniline Compounds);0 (Biomarkers);0 (Quinolines);0 (Radiopharmaceuticals);0 (thk5351);0 (tau Proteins);Aged;Aged, 80 and over;Alzheimer Disease/diagnostic imaging/ metabolism;Aminopyridines/ pharmacokinetics;Aniline Compounds/ pharmacokinetics;Biomarkers/metabolism;Brain/diagnostic imaging/ metabolism;Female;Humans;Isotope Labeling/methods;Male;Metabolic Clearance Rate;Middle Aged;Molecular Imaging/ methods;Positron-Emission Tomography/ methods;Protein Binding;Quinolines/ pharmacokinetics;Radiopharmaceuticals/pharmacokinetics;Reproducibility of Results;Sensitivity and Specificity;Tissue Distribution;tau Proteins/ metabolism;Alzheimer's disease;Thk;positron emission tomography;quantitation;tau","Betthauser, T. J.;Lao, P. J.;Murali, D.;Barnhart, T. E.;Furumoto, S.;Okamura, N.;Stone, C. K.;Johnson, S. C.;Christian, B. T.",2017,Jun,,0,
5362,In vivo comparison of tau radioligands 18F-THK-5351 and 18F-THK-5317,"PURPOSE: This study compared the in vivo imaging characteristics of tau positron emission tomography (PET) ligands 18 F-THK-5351 and 18F-THK-5317 in the context of Alzheimer's disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and standard uptake value ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification. METHODS: Twenty-eight subjects (mean age 71+/-7yrs) underwent either dynamic 90-minute 18F-THK-5317 or 18F-THK-5351 PET scans. Bland-Altman plots were utilized to compare the simplified reference tissue method (SRTM), multilinear reference tissue method (MRTM2), and Logan reference tissue DVR estimates and to assess temporal stability of SUVR windows using cerebellar gray matter (GM) as a reference region. In vivo kinetics and DVR estimates were directly compared for 10 subjects that underwent both 18F-THK-5317 and 18F-THK-5351 PET scans. RESULTS: THK-5351 exhibited faster cerebellar GM clearance, faster cortical white matter (WM) clearance, and higher DVR estimates in AD tau-associated regions of interest (ROIs) compared to THK-5317. The MRTM2 method produced the most reliable DVR estimates for both tracers, particularly when scan duration was shortened to 60 minutes. SUVR stability was observed 50-70 minutes post injection for both tracers. Parametric images revealed differences between MRTM2, Logan and SUVR binding in WM regions for THK-5317. CONCLUSION: THK-5317 and THK-5351 show promise for in vivo detection of AD tau. THK-5351 has more favorable pharmacokinetics and imaging characteristics compared to THK-5317.",Alzheimer's disease;Pet;Positron emission tomography;Radiopharmaceuticals;Radiotracer Tissue Kinetics;Thk;quantitation;tau,"Betthauser, T.;Lao, P. J.;Murali, D.;Barnhart, T. E.;Furumoto, S.;Okamura, N.;Stone, C. K.;Johnson, S. C.;Christian, B. T.",2016,Nov 10,,0,
5363,Retinal vasoreactivity as a marker for chronic ischemic white matter disease?,"The cerebral microvasculature cannot be easily studied non-invasively. Because the retina and brain share embryological, anatomical and physiological similarities, studies of retinal blood vessels may prove to be useful as a surrogate marker for cerebrovascular disease. In epidemiological studies abnormal retinal arteriovenous ratios (AVRs) predict the risk of stroke and vascular dementia. However, the association between retinal vasoreactivity, cerebral small vessel ischemic disease, and cerebral blood vessel function remains unknown. STUDY GOALS: To examine (1) the association between cerebral ischemic white matter disease (WMD) and retinal microvessel behavior and (2) the relationship between retinal blood vessel reactivity and measures of cerebrovascular function. METHODS: Cohort study of 12 patients with ischemic WMD and 14 healthy controls. Retinal vasoreactivity was measured following high frequency flicker light stimulation. Middle cerebral artery (MCA) vasoreactivity was measured using transcranial Doppler ultrasound (TCD). Magnetic resonance imaging scans (MRIs) were reviewed for evidence of ischemic WMD. RESULTS: Patients with ischemic WMD had attenuated retinal venous (2.2% +/- 0.27 SD, vs. controls 6% +/- 0.7 SD, p=0.002, CI 95%) and arterial (1.9% +/- 0.8 SD, vs. controls 4.9% +/- 0.8 SD, p=0.004, CI 95%) vasoreactivity compared to controls. An attenuated retinal venous light flicker response was associated with a significant decrease of MCA vasoreactivity (r=0.45, p=0.05, CI 95%). Decreased AVRs, an indicator for altered retinal vessel architecture in patients with cerebral chronic ischemic WMD, were also significantly correlated with dysfunction of cerebral vasoreactivity (r=0.69, p=0.001, CI 95%). CONCLUSION: In this study functional and structural impairment of the retinal microvasculature were associated with ischemic WMD and measures of cerebral vascular function. Microvascular dysfunction in the eye may predict cerebral small vessel disease, but validation by larger studies is needed.","Adult;Aged;Aged, 80 and over;Brain/ pathology;Chronic Disease;Female;Humans;Leukoencephalopathies/complications/ pathology;Linear Models;Magnetic Resonance Imaging;Male;Middle Aged;Reproducibility of Results;Retinal Vessels/pathology/ physiopathology;Stroke/complications/ pathology;Ultrasonography, Doppler, Transcranial","Bettermann, K.;Slocomb, J. E.;Shivkumar, V.;Lott, M. E.",2012,Nov 15,10.1016/j.jns.2012.05.041,0,
5364,Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes,"Diabetes is a common cause of small vessel disease leading to stroke and vascular dementia. While the function and structure of large cerebral vessels can be easily studied, the brain's microvasculature remains difficult to assess. Previous studies have demonstrated that structural changes in the retinal vessel architecture predict stroke risk, but these changes occur at late disease stages. Our goal was to examine whether retinal vascular status can predict cerebral small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity and cerebral vascular function were measured in 78 subjects (19 healthy controls, 22 subjects with prediabetes, and 37 with type-2 diabetes) using a new noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with disease progression of diabetes. Similarly, retinal vascular reactivity was significantly attenuated in subjects with prediabetes and diabetes compared to healthy controls. Subjects with prediabetes and diabetes with impaired cerebral vasoreactivity showed mainly attenuation of the retinal venous flicker response. This is the first study to explore the relationship between retinal and cerebral vascular function in diabetes. Impairment of venous retinal responsiveness may be one of the earliest markers of vascular dysfunction in diabetes possibly indicating subsequent risk of stroke and vascular dementia.",Retinal vasoreactivity;Tcd;optic imaging,"Bettermann, K.;Slocomb, J.;Shivkumar, V.;Quillen, D.;Gardner, T. W.;Lott, M. E.",2017,Jan,,0,
5365,Calcium antagonists and multi-infarct dementia: A trial involving sequential NMR and psychometric assessment,A double-blind placebo-controlled trial of the calcium antagonist Nimodipine in 10 patients with multi-infarct dementia (MID) shows that there is no improvement when compared with 10 patients on placebo assessed by clinical ratings and sequential NMR imaging. The value of repeated NMR imaging in measuring changes in MID is described.,,"Besson, J. A. O.;Palin, A. N.;Ebmeier, K. P.;Eagles, J. M.;Smith, F. W.",1988,1988,,0,
5366,Nuclear magnetic resonance (NMR). II. Imaging in dementia,"Proton NMR imaging of the brain is rapidly becoming established as a useful investigative tool in medicine. This paper examines the usefulness of the NMR parameters - spin-lattice relaxation time (T(1)) and proton density (PD) - in differentiating groups of patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) from each other, and from elderly controls. T(1) values increase with severity of dementia. NMR parameters may also be of use in localising regions of brain damage.",,"Besson, J. A. O.;Corrigan, F. M.;Foreman, E. I.",1985,1985,,0,
5367,Post-mortem proton magnetic resonance spectrometric measures of brain regions in patients with a pathological diagnosis of Alzheimer's disease and multi-infarct dementia,"In-vitro spectrometric measures were made of spin-lattice (T(1)) and spin-spin (T(2)) relaxation times of samples of grey and white matter from the brains of 15 patients with a pathological diagnosis of Alzheimer's disease, 5 with multi-infarct dementia, and 11 non-demented subjects. Relaxation times were significantly greater in the parietal white matter and temporal white matter of patients with Alzheimer's disease compared with that of the other subjects. This was associated with an increase in tissue water content. These findings confirm measures obtained in some imaging studies.",,"Besson, J. A. O.;Best, P. V.;Skinner, E. R.",1992,1992,,0,
5368,The relationship between Parkinson's disease and dementia. A study using proton NMR imaging parameters,"The value of the spin lattice relaxation time (T1) obtained during nuclear magnetic resonance imaging of the brain was studied in patients with idiopathic Parkinson's disease, with and without dementia. T1 increases significantly in the basal ganglia and cerebral white matter of the demented and non-demented groups. T1 of the cerebral white matter correlates with the severity of dementia.",Aged;Brain;Dementia/complications/ diagnosis;Globus Pallidus;Humans;Magnetic Resonance Spectroscopy;Middle Aged;Parkinson Disease/complications/ diagnosis;Putamen;Time Factors,"Besson, J. A.;Mutch, W. J.;Smith, F. W.;Corrigan, F. M.",1985,Oct,,0,
5369,[Relation between Parkinson disease and dementia conditions studied with proton NMR imaging parameters] Das Verhaltnis zwischen M. Parkinson und Demenzzustanden untersucht mit Hilfe von Protonen-NMR-Abbildungsparametern,The value of the spin lattice relaxation time (T1) obtained during nuclear magnetic resonance imaging of the brain in patients with Idiopathic Parkinson's disease with and without dementia is studied. T1 increases significantly in the basal ganglia and cerebral white matter of the demented and nondemented groups. T1 of the cerebral white matter correlates with the severity of dementia.,Aged;Brain/ pathology;Cerebral Cortex/pathology;Dementia/ pathology;Globus Pallidus/pathology;Humans;Intracranial Arteriosclerosis/pathology;Magnetic Resonance Spectroscopy;Parkinson Disease/ pathology;Putamen/pathology;Substantia Nigra/pathology,"Besson, J. A.;Mutch, W. J.;Downie, A. W.;Smith, F. W.;Corrigan, F. M.;Ashcroft, G. W.;Crosher, G. A.",1985,Nov-Dec,,0,
5370,Relation between Parkinson disease and dementia conditions studied with proton NMR imaging parameters,The value of the spin lattice relaxation time (T1) obtained during nuclear magnetic resonance imaging of the brain in patients with Idiopathic Parkinson's disease with and without dementia is studied. T1 increases significantly in the basal ganglia and cerebral white matter of the demented and nondemented groups. T1 of the cerebral white matter correlates with the severity of dementia.,Aged;Brain/ pathology;Cerebral Cortex/pathology;Dementia/ pathology;Globus Pallidus/pathology;Humans;Intracranial Arteriosclerosis/pathology;Magnetic Resonance Spectroscopy;Parkinson Disease/ pathology;Putamen/pathology;Substantia Nigra/pathology,"Besson, J. A.;Mutch, W. J.;Downie, A. W.;Smith, F. W.;Corrigan, F. M.;Ashcroft, G. W.;Crosher, G. A.",1985,Nov-Dec,,0,
5371,Do white matter changes on MRI and CT differentiate vascular dementia from Alzheimer's disease?,,"Aged;Alzheimer Disease/*pathology;Brain/pathology;Dementia/*pathology;Diagnosis, Differential;Humans;*Magnetic Resonance Imaging;*Tomography, X-Ray Computed","Besson, J. A.;Ebmeier, K. P.;Best, P. V.;Smith, F. W.",1988,Feb,,0,
5372,"Magnetic resonance imaging in Alzheimer's disease, multi-infarct dementia, alcoholic dementia and Korsakoff's psychosis","Regional spin lattice relaxation times (T1) measured during nuclear magnetic resonance imaging of the brain were compared in patients with Alzheimer's disease, multi-infarct dementia, alcoholic dementia, Korsakoff's psychosis and control subjects. Regional differences were found between all patient groups compared with controls and within patient groups, with the exception of the comparison between Korsakoff's psychosis and alcoholic dementia. Correlations between regional T1 change and cognitive test scores were also found, with particular emphasis between visuospatial deficits and parietal T1. The possible role of T1 measures in the pathophysiology of these disorders is discussed.","Aged;Alcohol Amnestic Disorder/ diagnosis;Alzheimer Disease/ diagnosis/psychology;Brain/ pathology;Dementia, Multi-Infarct/ diagnosis/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychometrics;Psychoses, Alcoholic/ diagnosis/psychology","Besson, J. A.;Crawford, J. R.;Parker, D. M.;Smith, F. W.",1989,Nov,,0,
5373,"Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes","Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.","Aged;Alzheimer Disease/ diagnosis/pathology/psychology;Amphetamines;Blood Flow Velocity/physiology;Brain/ pathology;Cerebral Arteries/pathology;Cerebral Cortex/blood supply;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Organotechnetium Compounds;Oximes;Psychometrics;Regional Blood Flow/physiology;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon","Besson, J. A.;Crawford, J. R.;Parker, D. M.;Ebmeier, K. P.;Best, P. V.;Gemmell, H. G.;Sharp, P. F.;Smith, F. W.",1990,Aug,,0,
5374,[NMR imaging in dementia states. A diagnostic and quantitative study] NMR-imaging in Demenzzustanden. Eine diagnostische und quantitative studie,Spin lattic relaxation times (T1) and proton density derived from proton nuclear magnetic resonance imaging data are measured in elderly patients with senile dementia of Alzheimer type (SDAT) and multi infarct dementia (MID) and the results compared with elderly controls. T1 values of the cerebral white matter are increased in the dementia groups and there is a statistical correlation with severity. Patients with SDAT have significantly differing proton density measures in cerebral white matter from those with MID. The potential value of these results are discussed together with the possible application to identify regional areas of damage.,"Aged;Alzheimer Disease/ diagnosis/psychology;Dementia/ diagnosis/psychology;Diagnosis, Differential;Humans;Magnetic Resonance Spectroscopy;Mental Status Schedule","Besson, J. A.;Corrigan, F. M.;Foreman, E. I.;Eastwood, L. M.;Smith, F. W.;Ashcroft, G. W.",1984,May-Jun,,0,
5375,NMR imaging in dementia states. A diagnostic and quantitative study,Spin lattic relaxation times (T1) and proton density derived from proton nuclear magnetic resonance imaging data are measured in elderly patients with senile dementia of Alzheimer type (SDAT) and multi infarct dementia (MID) and the results compared with elderly controls. T1 values of the cerebral white matter are increased in the dementia groups and there is a statistical correlation with severity. Patients with SDAT have significantly differing proton density measures in cerebral white matter from those with MID. The potential value of these results are discussed together with the possible application to identify regional areas of damage.,"Aged;Alzheimer Disease/ diagnosis/psychology;Dementia/ diagnosis/psychology;Diagnosis, Differential;Humans;Magnetic Resonance Spectroscopy;Mental Status Schedule","Besson, J. A.;Corrigan, F. M.;Foreman, E. I.;Eastwood, L. M.;Smith, F. W.;Ashcroft, G. W.",1984,May-Jun,,0,
5376,Differentiating senile dementia of Alzheimer type and multi-infarct dementia by proton NMR imaging,,"Aged;Alzheimer Disease/ diagnosis;Dementia/ diagnosis;Diagnosis, Differential;Humans;Magnetic Resonance Spectroscopy","Besson, J. A.;Corrigan, F. M.;Foreman, E. I.;Ashcroft, G. W.;Eastwood, L. M.;Smith, F. W.",1983,Oct 1,,0,
5377,Discovering Alzheimer's disease and bipolar disorder white matter effects building computer aided diagnostic systems on brain diffusion tensor imaging features,"The aim of this study is to look for differential effects in white matter (WM) of bipolar disorder (BD) and Alzheimer's disease (AD) patients. We proceed by investigating the feasibility of discriminating between BD and AD patients, and from healthy controls (HC), using multivariate data analysis based on diffusion tensor imaging (DTI) data features. Specifically, support vector machine (SVM) classifiers were trained and tested on fractional anisotropy (FA). Voxel sites are selected as features for classification if their Pearson's correlation between FA values at voxel site across subjects and the indicative variable specifying the subject class is above the threshold set by a percentile of its empirical distribution. To avoid double dipping, selection was performed only on training data in a leave one out cross-validation study. Classification results show that FA features and a linear SVM classifier achieve perfect accuracy, sensitivity and specificity in AD vs. HC, BD vs. HC, and AD vs. BD leave-one-out cross-validation studies. The localization of the discriminant voxel sites on a probabilistic tractography atlas shows effects on seven major WM tracts in each hemisphere and two commissural tracts.",Aged;Alzheimer Disease/ diagnosis/pathology;Anisotropy;Bipolar Disorder/ diagnosis/pathology;Brain/ pathology;Computer-Aided Design;Diffusion Tensor Imaging;Feasibility Studies;Female;Humans;Male;Probability;Support Vector Machine,"Besga, A.;Termenon, M.;Grana, M.;Echeveste, J.;Perez, J. M.;Gonzalez-Pinto, A.",2012,Jun 27,10.1016/j.neulet.2012.05.033,0,
5378,Eigenanatomy on Fractional Anisotropy Imaging Provides White Matter Anatomical Features Discriminating Between Alzheimer's Disease and Late Onset Bipolar Disorder,"BACKGROUND: Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging. Biomarkers extracted from blood plasma are not discriminant because both pathologies share pathophysiological features related to neuroinflammation, therefore we look for anatomical features highly correlated with blood biomarkers that allow accurate diagnosis prediction. This may shed some light on the basic biological mechanisms leading to one or another disease. Moreover, accurate diagnosis is needed to select the best personalized treatment. OBJECTIVE: We look for white matter features which are correlated with blood plasma biomarkers (inflammatory and neurotrophic) discriminating LOBD from AD. MATERIALS: A sample of healthy controls (HC) (n=19), AD patients (n=35), and BD patients (n=24) has been recruited at the Alava University Hospital. Plasma biomarkers have been obtained at recruitment time. Diffusion weighted (DWI) magnetic resonance imaging (MRI) are obtained for each subject. METHODS: DWI is preprocessed to obtain diffusion tensor imaging (DTI) data, which is reduced to fractional anisotropy (FA) data. In the selection phase, eigenanatomy finds FA eigenvolumes maximally correlated with plasma biomarkers by partial sparse canonical correlation analysis (PSCCAN). In the analysis phase, we take the eigenvolume projection coefficients as the classification features, carrying out cross-validation of support vector machine (SVM) to obtain discrimination power of each biomarker effects. The John Hopkins Universtiy white matter atlas is used to provide anatomical localizations of the detected feature clusters. RESULTS: Classification results show that one specific biomarker of oxidative stress (malondialdehyde MDA) gives the best classification performance ( accuracy 85%, F-score 86%, sensitivity, and specificity 87%, ) in the discrimination of AD and LOBD. Discriminating features appear to be localized in the posterior limb of the internal capsule and superior corona radiata. CONCLUSION: It is feasible to support contrast diagnosis among LOBD and AD by means of predictive classifiers based on eigenanatomy features computed from FA imaging correlated to plasma biomarkers. In addition, white matter eigenanatomy localizations offer some new avenues to assess the differential pathophysiology of LOBD and AD.",,"Besga, A.;Chyzhyk, D.;Gonzalez-Ortega, I.;Savio, A.;Ayerdi, B.;Echeveste, J.;Grana, M.;Gonzalez-Pinto, A.",2016,,,0,
5379,White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers,"Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.",Alzheimer disease;inflammatory biomarkers;late onset bipolar disorder;multimodal brain data analysis;nerve growth factors;tract based spatial statistics,"Besga, A.;Chyzhyk, D.;Gonzalez-Ortega, I.;Echeveste, J.;Grana-Lecuona, M.;Grana, M.;Gonzalez-Pinto, A.",2017,,,0,
5380,Differences in brain cholesterol metabolism and insulin in two subgroups of patients with different CSF biomarkers but similar white matter lesions suggest different pathogenic mechanisms,"Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF Abeta42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated.",Aged;Alzheimer Disease/metabolism/pathology;Amyloid beta-Peptides/ cerebrospinal fluid;Basal Ganglia/pathology;Biomarkers/cerebrospinal fluid;Brain/ metabolism/pathology;Cholesterol/blood/cerebrospinal fluid/ metabolism;Female;Humans;Insulin/cerebrospinal fluid/ metabolism;Lanosterol/blood/metabolism;Magnetic Resonance Imaging;Male;Memory Disorders/ metabolism/pathology;Middle Aged;Peptide Fragments/ cerebrospinal fluid;tau Proteins/ cerebrospinal fluid,"Besga, A.;Cedazo-Minguez, A.;Kareholt, I.;Solomon, A.;Bjorkhem, I.;Winblad, B.;Leoni, V.;Hooshmand, B.;Spulber, G.;Gonzalez-Pinto, A.;Kivipelto, M.;Wahlund, L. O.",2012,Feb 29,10.1016/j.neulet.2012.01.017,0,
5381,"A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis","In this pilot study, 72 non-demented and non-depressive elderly hypertensive patients with evidence of leukoaraiosis on cerebral computed tomography scan (Rezek score: > 16) were randomly assigned to receive either nicergoline 30 mg b.i.d. (n = 36) or a placebo (n = 36) for 24 months. All patients received antihypertensives and their hypertension was controlled under treatment. They were evaluated by nine neuropsychological tests exploring memory, concentration, verbal and motor performances, administered at baseline and at every six-month interval during the study period. At baseline, the two groups were comparable for all demographic and clinical characteristics, including cognitive functions, except for the delayed recall of the Auditory Verbal Learning Test (AVLT), which was better in the placebo group (P = 0.04). Changes in scores over time were compared between the two groups. At the last visit, patients on nicergoline (n = 31) were found to have deteriorated less or to have improved more on test scores than the patients on placebo (n = 30). Significant differences were observed for memory function (AVLT short term recall, P = 0.026; AVLT delayed recall, P = 0.013; and, Benton Visual Retention Test, P = 0.002) and attention and concentration (Letter Cancellation Test, P = 0.043; and, WAIS-R Digit Symbol subtest, P = 0.006). The Rezek score remained unchanged in the two groups. Tolerance of nicergoline was similar to that of placebo. In conclusion, this study shows that nicergoline 30 mg b.i. d. administered over a 24-month period attenuates the deterioration in cognitive functions in elderly hypertensive patients with leukoaraiosis. Whether these effects were specific for this type of white matter changes could not be determined in the context of this pilot study.","Aged;Aged, 80 and over;Dementia, Vascular/complications/*drug therapy/psychology;Double-Blind Method;Drug Administration Schedule;Female;Humans;Hypertension/complications/*drug therapy;Male;Middle Aged;Neuropsychological Tests;Nicergoline/*administration & dosage/*adverse effects;Pilot Projects;Time Factors","Bes, A.;Orgogozo, J. M.;Poncet, M.;Rancurel, G.;Weber, M.;Bertholom, N.;Calvez, R.;Stehle, B.",1999,May,,0,
5382,Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations,"Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions.",Aged;Color Perception/ physiology;Color Vision Defects/etiology/ physiopathology;Female;Humans;Magnetic Resonance Imaging/methods;Male;Middle Aged;Parkinson Disease/ complications/pathology/physiopathology,"Bertrand, J. A.;Bedetti, C.;Postuma, R. B.;Monchi, O.;Genier Marchand, D.;Jubault, T.;Gagnon, J. F.",2012,Dec,10.1002/mds.25272,0,
5383,Juvenile arteriosclerotic leukoencephalopathy. Clinico-pathological study of one case,"A 34-year old right-handed man was suffering from recurrent cerebro-vascular insults. CT-scans revealed several subcortical lacunar infarcts, and leukoaraiosis. Arteriography of the left and the right carotid arteries was performed respectively on the 4th and the 9th year of the disease, and did not elicit significant extracranial and intracranial vascular lesions. There were no arguments in favor of infectious, inflammatory, or auto-immune vascular diseases. The patient had tardive hypertension and dementia, and died at the age of 44. Pathological findings, limited to the brain and cervical spinal cord, revealed numerous ischemic lacunar infarcts. Histological lesions were consistent with the diagnosis of arteriosclerotic leukoencephalopathy. There were oedema, palor, and loss of myelin in the white matter, and nonspecific diffuse arteriosclerotic lesions that were particularly pronounced in the intimal part of the arterial wall. No inflammatory process nor amyloid deposits were found. Despite the onset of the disease in a young adult and the late occurrence of hypertension, our case report shares most of the pathological features of the Binswanger's type of arteriosclerotic encephalopathy.",adult;arteriosclerosis;article;case report;dementia;human;human tissue;hypotension;leukoencephalopathy;male;priority journal,"Berthier, E.;Broussolle, E.;Garcia-Jacquier, M.;Tommasi, M.;Chazot, G.",1992,,,0,
5384,Statins and cognitive function in the elderly: the Cardiovascular Health Study,"OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults. METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.","Aged;Aged, 80 and over;Aging/drug effects/metabolism/pathology;Anticholesteremic Agents/pharmacology/therapeutic use;Atrophy/*drug therapy/physiopathology/prevention & control;Brain/*drug effects/metabolism/physiopathology;Cholesterol/blood;Cognition Disorders/*drug therapy/physiopathology/prevention & control;Cohort Studies;Dementia/*drug therapy/physiopathology/prevention & control;Female;Humans;Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/therapeutic use;Longitudinal Studies;Male;Memory Disorders/drug therapy/physiopathology/prevention & control;Nootropic Agents/*pharmacology/therapeutic use;Treatment Outcome","Bernick, C.;Katz, R.;Smith, N. L.;Rapp, S.;Bhadelia, R.;Carlson, M.;Kuller, L.",2005,Nov 8,10.1212/01.wnl.0000182897.18229.ec,0,
5385,Contribution of Magnetic Resonance (MR) in diagnosis of some forms of organic dementia,"The authors present neuroradiological semeiotic elements on Magnetic Resonance (MR) in some more frequent forms of organic dementia including Alzheimer's, vascular dementia, frontotemporal dementia, and Creutzfeld- Jakob's disease, emphasizing useful aspects in diagnosis. MR assists good anatomical evaluation of the gray matter, cortical and subcortical structures, involved in diverse forms of organic dementia and contributes also in early phases of diagnosis. High spatial resolution permits identification of indices for anatomic evaluation of these structures, specifically the superficial and volumetric linear indices which are utilized in the study of mesial-temporal structures in Alzheimer's disease. MR with 'diffuse and focal atrophy' morphology and its quantification also provides information on signal intensity of encephalic structures in various sequences. In particular, the evaluation of alterations of white matter, which in diverse measure and mode may be associated with organic dementia, constitute an element in differential diagnosis. Moreover, signal analysis of the white and gray matter may be considered not only 'visual' but may also be quantified using sample processes or computerized tissue segmentation.",Alzheimer disease;article;brain cortex atrophy;Creutzfeldt Jakob disease;dementia;differential diagnosis;early diagnosis;frontotemporal dementia;gray matter;hippocampus;human;multiinfarct dementia;neuroradiology;nuclear magnetic resonance imaging;white matter,"Bernardi, B.;Pantieri, R.;Falcini, M.;Leonardi, M.",1998,,,0,
5386,Neuropsychiatric correlates of white matter hyperintensities in Alzheimer's disease,"OBJECTIVE: To investigate the association of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures of brain atrophy and white matter hyperintensities (WMH). METHODS: Thirty-seven patients with probable AD received the Neuropsychiatric Inventory (NPI), the Mini Mental Status Exam (MMSE), and an MRI scan as part of their initial evaluation at the Outpatient Memory Diagnostic Clinic at McLean Hospital. MRI-based volumetric measurements of whole brain atrophy, hippocampal volumes, and WMH were obtained. Analysis of covariance models, using age as a covariate and the presence of specific BPSD as independent variables, were used to test for differences in whole brain volumes, hippocampal volumes and WMH volumes. RESULTS: Increased WMH were associated with symptoms of anxiety, aberrant motor behavior, and night time disturbance, while symptoms of disinhibition were linked to lower WMH volume. No associations were found for whole brain or hippocampal volumes and BPSD. CONCLUSIONS: These findings suggest that white matter changes are associated with the presence of BPSD in AD.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/ pathology/ psychology;Analysis of Variance;Brain/ pathology;Brief Psychiatric Rating Scale;Cross-Sectional Studies;Female;Hippocampus/pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Retrospective Studies","Berlow, Y. A.;Wells, W. M.;Ellison, J. M.;Sung, Y. H.;Renshaw, P. F.;Harper, D. G.",2010,Aug,10.1002/gps.2418,0,
5387,Cerebral amyloid angiopathy and dementia,"Cerebral amyloid angiopathy (CAA) is one of the most frequent causes of intracerebral hemorrhage (ICH). The deposition of beta amyloid leads to vascular fragility due to degeneration of vessel walls, formation of microaneurysms particularly in cortical blood vessels and fibrinoid vessel wall necrosis. The Congo red positive amyloid deposits are biochemically similar to the material comprising senile plaques in Alzheimer's disease. Recurrent or multiple simultaneous hemorrhages particularly in older patients should raise the suspicion of CAA. Gradient echo magnetic resonance imaging (MRI) is a sensitive, non-invasive technique for identifying even very small hemorrhages and superficial siderosis, which may cause transient symptoms in CAA. There is also a correlation between CAA, microbleeding and cognitive decline. Inflammatory variants of CAA must be suspected whenever patients present with progressive dementia, headache and multifocal symptoms in association with CAA findings in MRI. Histopathologically, a distinction is made between CAA-related inflammation (CAA-ri) with perivascular inflammatory infiltrates and amyloid beta-related angiitis (ABRA) with histological detection of transmural vasculitis. Inflammatory variants should be treated with corticosteroids and immunosuppressants.",,"Berlit, P.;Keyvani, K.;Kramer, M.;Weber, R.",2015,Oct,10.1007/s00115-015-4407-5,0,
5388,Neuropsychiatric disease in collagen vascular diseases and vasculitis,"The prevalence of neuropsychiatric symptoms in systemic lupus erythematosus varies between 37 and 95%; cognitive dysfunction, mood disorder, and anxiety syndromes are especially frequent. In Sjoegren's syndrome, cognitive dysfunction is combined with frontal executive disorder and attention deficit. Memory impairment, frontal executive dysfunction and personality changes have been reported in Behçet's disease. Classic polyarteritis nodosa, the Churg Strauss syndrome and Wegener's granulomatosis may be associated with cognitive changes due to inflammatory encephalopathy. Cranial arteritis belongs to the treatable causes of dementia. In primary angiitis of the CNS, small-vessel disease presents more frequently with encephalopathy. © 2007 Steinkopff-Verlag.",corticosteroid;cyclophosphamide;antibody screening;anxiety disorder;article;Behcet disease;brain disease;brain vasculitis;central nervous system;Churg Strauss syndrome;cognition;cognitive defect;collagen disease;dementia;disease association;human;leptomeninx;memory disorder;mental disease;mood disorder;motor performance;multiple sclerosis;neuropsychiatry;nuclear magnetic resonance imaging;polyarteritis nodosa;priority journal;single photon emission computer tomography;Sjoegren syndrome;systemic lupus erythematosus;temporal arteritis;Wegener granulomatosis,"Berlit, P.",2007,,,0,
5389,Extensive white-matter changes in case of adult polyglucosan body disease,"Extensive white matter signal changes were observed on T2-weighted images of a 49-year-old man. He presented with a slowly progressive gait disorder, and finally developed severe dementia. Extensive metabolic and infectious investigations failed to disclose the underlying cause during life. Autopsy revealed adult polyglucosan body disease. We discuss MRI findings likely to permit this diagnosis if combined with clinical findings and nerve or skin biopsy.",,"Berkhoff, M.;Weis, J.;Schroth, G.;Sturzenegger, M.",2001,2001,,0,
5390,EEG in cerebrotendinous xanthomatosis (CTX),"Cerebrotendinous xanthomatosis (CTX) is a rare hereditary lipid storage disease first described by Van Bogaert et al. in 1937. Its main manifestations include CNS involvement, ocular cataracts and xanthomata of Achilles as well as other tendons and tissues. The neurological features are progressive dementia, ataxia and spastic quadriparesis. Mild peripheral neuropathy has been observed and convulsions have been described in several patients. Biochemical examinations demonstrate normal plasma cholesterol and high cholestanol levels, which are diagnostic for CTX. It was suggested that the lipid abnormality results from a block in bile acid synthesis in the liver with subnormal production of chenodeoxycholic acid (CDCA) and defective high density lipoprotein metabolism. Recently it has been suggested that the basic metabolic defect in CTX is due to hepatic mitochondrial enzyme abnormality. Treatment with chenodeoxycholic acid (CDCA) may stop the progression and possibly reverse some of the manifestations of CTX. Cranial CT scans demonstrated diffuse white matter hypodensity indicative of demyelination both supratentorially and infratentorially. A cerebellar xanthoma was suggested in one of 9 CT examined cases. The results of EEG studies were only briefly noted in several publications. This work has two goals, firstly to describe the EEG pattern in CTX and secondly, to evaluate the possible EEG changes following treatment with chenodeoxycholic acid (CDCA), 250 mg, three times daily, orally.",chenodeoxycholic acid;central nervous system;cerebrotendinous xanthomatosis;diagnosis;electroencephalography;major clinical study,"Berginer, V. M.;Radwan, H.;Korczyn, A. D.",1982,,,0,
5391,Atypical sporadic CJD-MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease,"We describe an atypical neuropathological phenotype of sporadic Creutzfeldt-Jakob disease in a 76-year-old man. The clinical symptoms were characterized by progressive dementia, gait ataxia, rigidity and urinary incontinence. The disease duration was 6 weeks. MRI did not show prominent atrophy or hyperintensities in cortical areas, striatum or thalamus. Biomarker examination of the cerebrospinal fluid deviated from that seen in pure Alzheimer's disease. Triphasic waves in the EEG were detected only later in the disease course, while 14-3-3 assay was positive. PRNP genotyping revealed methionine homozygosity (MM) at codon 129. Neuropathology showed classical CJD changes corresponding to the MM type 1 cases. However, a striking feature was the presence of abundant kuru-type plaques in the white matter. This rare morphology was associated with neuropathological signs of intranuclear inclusion body disease and advanced stage of argyrophilic grain disease. These alterations did not show correlation with each other, thus seemed to develop independently. This case further highlights the complexity of neuropathological alterations in the ageing brain.",aging;Alzheimer disease;assay;ataxic gait;atrophy;brain;cell nucleus inclusion body;cerebrospinal fluid;codon;corpus striatum;Creutzfeldt Jakob disease;dementia;disease course;disease duration;electroencephalogram;examination;genotype;grain;homozygosity;human;kuru;male;morphology;neuropathology;nuclear magnetic resonance imaging;phenotype;prion;rigidity;sporadic Creutzfeldt Jakob disease;thalamus;urine incontinence;white matter;biological marker;methionine,"Berghoff, A. S.;Trummert, A.;Unterberger, U.;Ströbel, T.;Hortobágyi, T.;Kovacs, G. G.",2015,,,0,
5392,Role of cortical microbleeds in cognitive impairment: In vivo behavioral and imaging characterization of a novel murine model,"Cerebral microbleeds (CMBs) could contribute to cognitive impairment in the general population and in patients with dementia. We designed a study to (i) develop a murine model of CMBs, (ii) assess whether CMBs affect cognition in this model and (iii) assess whether this model is sensitive to pharmacological modulation. Male C57Bl6/J mice were stereotactically administered collagenase to induce cortical lesion analysed by MRI at 24 h. CMB-mice were assessed at six weeks post-lesion for cognitive performances (Barnes maze and Touchscreen automated paired-associated learning (PAL) task) and for cerebral metabolism (in vivo PET/CT with fluorodeoxyglucose (FDG)). CMB-model sensitivity to pharmacological modulation was assessed by administering atorvastatin (5 mg/kg/day) over the follow-up period. CMB mice were compared to naive littermates. Collagenase at 0.8 microU/microl appeared suitable to induce reproducible and reliable CMBs. At six weeks, a decline in learning, spatial and visuospatial memory was significantly observed in CMB-mice. Brain metabolism was impaired in all cortex, striatum and the ipsilateral dentate gyrus. A significant improvement in cognition performances was depicted under atorvastatin. In this novel murine model of CMBs, we validated that CMBs lowered cognitive performances and affected regional metabolism. We also proved that this CMB-model is sensitive to pharmacological modulation.",Cognitive impairment;microbleed;pharmacological modulation;preclinical model;rodents,"Bergeron, S.;Chen, Y.;Auger, F.;Deguil, J.;Durieux, N.;Skrobala, E.;Barus, R.;Potey, C.;Cordonnier, C.;Pasquier, F.;Ravasi, L.;Bordet, R.;Gautier, S.",2018,Jan 1,,0,
5393,Cerebrovascular changes in the basal ganglia with HIV dementia,"BACKGROUND: HIV dementia is a form of subcortical dementia. Clinical, radiologic, pathologic, and biochemical studies suggest a major contribution of basal ganglia dysfunction to the pathogenesis of this disorder. Many investigators have proposed a contribution of a disrupted blood-brain barrier (BBB) to the pathogenesis of HIV dementia. OBJECTIVE: To identify microvascular abnormalities in vivo in basal ganglia or white matter of persons with HIV dementia. METHODS: Time course of MRI postcontrast enhancement was determined in basal ganglia and white matter of HIV-infected persons without dementia (Memorial Sloan Kettering [MSK] score of 0; n = 4); HIV-infected persons with mild dementia (MSK score of 0.5; n = 2); and HIV-infected persons with moderate-to-severe dementia (MSK > or = 1.0; n = 6). RESULTS: Increased basal ganglia enhancement was observed in individuals with moderate-to-severe dementia relative to nondemented individuals, both immediately and 30 minutes after contrast administration. Decline of basal ganglia enhancement was slower in the moderately to severely demented patients and, when normalized to intravascular enhancement of sagittal sinus, suggested leakage of contrast agent, consistent with increased permeability of BBB. A significant correlation between the postcontrast fractional enhancement at 30 minutes (FE30) and the MSK score was noted. White matter showed no significant differences in postcontrast enhancement among the three groups. CONCLUSION: Increased early enhancement in basal ganglia of the HIV dementia group is consistent with increased regional cerebral blood volume (rCBV). Increased late enhancement is strongly suggestive of BBB disruption. Similar abnormalities were absent in the white matter adjacent to the caudate nucleus.",AIDS Dementia Complex/*pathology/physiopathology;Adult;Basal Ganglia/*blood supply/*pathology;Cerebrovascular Circulation/*physiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Time Factors,"Berger, J. R.;Nath, A.;Greenberg, R. N.;Andersen, A. H.;Greene, R. A.;Bognar, A.;Avison, M. J.",2000,Feb 22,,0,
5394,CT appearance of panencephalopathic and ataxic type of Creutzfeldt-Jackob disease,"We present a proven case of Creutzfeldt-Jakob disease with severe involvement of white matter and cerebellum. Serial CT showed a unique pattern consisting of discrete cerebral and cerebellar atrophy, diffuse white matter hypodensity, and progressive enlargement of lateral and fourth ventricles.",adult;article;ataxia;autopsy;case report;cerebellum;computer assisted tomography;Creutzfeldt Jakob disease;diagnosis;female;histopathology;human;priority journal;white matter,"Berciano, J.;Diez, C.;Polo, J. M.;Pascual, J.;Figols, J.",1991,,,0,
5395,Assessment of damage to cerebral white matter fiber in the subacute phase after carbon monoxide poisoning using fractional anisotropy in diffusion tensor imaging,"INTRODUCTION: Chronic neuropsychiatric symptoms after carbon monoxide (CO) poisoning are caused by demyelination of cerebral white matter fibers. We examined whether diffusion tensor imaging can sensitively represent damage to fibers of the centrum semiovale in the subacute phase after CO intoxication. METHODS: Subjects comprised 13 adult patients with CO poisoning, classified into three groups according to clinical behaviors: group A, patients with transit acute symptoms only; group P, patients with persistent neurological symptoms; and group D, patients with ""delayed neuropsychiatric sequelae"" occurring after a lucid interval. Median fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the centrum semiovale bilaterally at 2 weeks were compared between these groups and a control group of ten healthy volunteers. Myelin basic protein (MBP) concentration in cerebrospinal fluid was examined at 2 weeks to evaluate the degree of demyelination in patients. RESULTS: MBP concentration was abnormal or detectable for all group P and group D patients but was undetectable for all patients assigned to group A. Low FA values in groups P and D displaying chronic neurological symptoms clearly differed from those in controls and group A without chronic neurological symptoms, but ADC showed no significant differences between patient groups. CONCLUSIONS: MBP concentration at 2 weeks after CO inhalation confirmed a certain extent of demyelination in the central nervous system of patients who would develop chronic neurological symptoms. In these patients, FA sensitively represented damage to white matter fibers in the centrum semiovale in the subacute phase after CO intoxication.","Adult;Anisotropy;Brain Damage, Chronic/diagnosis/pathology;Carbon Monoxide Poisoning/ diagnosis/pathology;Cerebral Cortex/ pathology;Chronic Disease;Cognition Disorders/ diagnosis/pathology;Dementia/ diagnosis/pathology;Demyelinating Diseases/ diagnosis/pathology;Diffusion Magnetic Resonance Imaging/ methods;Dominance, Cerebral/physiology;Female;Follow-Up Studies;Humans;Image Processing, Computer-Assisted/ methods;Imaging, Three-Dimensional/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Neurologic Examination;Neuropsychological Tests;Reference Values;Whole Body Imaging;Young Adult","Beppu, T.;Nishimoto, H.;Ishigaki, D.;Fujiwara, S.;Yoshida, T.;Oikawa, H.;Kamada, K.;Sasaki, M.;Ogasawara, K.",2010,Aug,10.1007/s00234-009-0649-x,0,
5396,Age-related white matter integrity differences in oldest-old without dementia,"Aging is known to have deleterious effects on cerebral white matter, yet little is known about these white matter alterations in advanced age. In this study, 94 oldest-old adults without dementia (90-103 years) underwent diffusion tensor imaging to assess relationships between chronological age and multiple measures of integrity in 18 white matter regions across the brain. Results revealed significant age-related declines in integrity in regions previously identified as being sensitive to aging in younger-old adults (corpus callosum, fornix, cingulum, external capsule). For the corpus callosum, the effect of age on genu fractional anisotropy was significantly weaker than the relationship between age and splenium fractional anisotropy. Importantly, age-related declines in white matter integrity did not differ in cognitively normal and cognitively impaired not demented oldest-old, suggesting that they were not solely driven by cognitive dysfunction or preclinical dementia in this advanced age group. Instead, white matter in these regions appears to remain vulnerable to normal aging processes through the 10th decade of life.","Aged, 80 and over;Aging/ pathology/psychology;Cognition;Corpus Callosum/diagnostic imaging/pathology;Diffusion Magnetic Resonance Imaging;Female;Fornix, Brain/diagnostic imaging/pathology;Humans;Male;Neuroimaging;White Matter/ diagnostic imaging/ pathology;Aging;Corpus callosum;Fornix;Oldest-old;White matter integrity","Bennett, I. J.;Greenia, D. E.;Maillard, P.;Sajjadi, S. A.;DeCarli, C.;Corrada, M. M.;Kawas, C. H.",2017,Aug,,0,
5397,Subcortical vascular disease and functional decline: A 6-year predictor study,"OBJECTIVES: To identify predictors of activity of daily living (ADL) and instrumental activity of daily living (IADL) decline in a population with subcortical vascular dementia (SVD) and to evaluate potential mechanism of decline. DESIGN: Longitudinal. SETTING: Hospital-based. PARTICIPANTS: Computed tomographic (CT) scanning identified 77 participants as having subcortical infarction. MEASUREMENTS: Participants were neurologically, neuropsychologically, behaviorally, and functionally assessed four times over 5.82 years. Baseline data were grouped into four modules: basic demographic and risk factor, CT scan, neurological and other clinical, and neuropsychological and behavioral. Multivariate analysis determined predictors of decline in ADLs and IADLs. RESULTS: Predictors of ADL decline were age, alcohol consumption, coordination, snout reflex, and performance on a neuropsychological test (Block Design). Predictors of IADL decline were predominantly cognitive and included the presence of paratonia and performance on the two neuropsychological tests (attention and memory tasks). CONCLUSION: These findings suggest that cognitive impairments are most likely to have an effect on IADL function, because the skills involved are complex and involve integrative activity, whereas physical and cognitive impairments combined are likely to compromise ADL function, given the more basic and physical nature of the functions involved. These findings indicate that in people with SVD, both ADL and IADL status should be monitored, because, for many, decline in function over time is likely, and thus the provision of appropriate support required.",adult;aged;alcohol consumption;article;attention;behavior;brain infarction;cognitive defect;computer assisted tomography;daily life activity;dementia;demography;female;human;longitudinal study;major clinical study;male;memory;multivariate analysis;neuropsychological test;nuclear magnetic resonance imaging;outcomes research;risk factor;statistical analysis;task performance;vascular disease,"Bennett, H. P.;Corbett, A. J.;Gaden, S.;Grayson, D. A.;Kril, J. J.;Anthony Broe, G.",2002,,,0,
5398,Clinical correlates of high signal lesions on magnetic resonance imaging in Alzheimer's disease,"The pathophysiology and clinical significance of high signal lesions, visualized on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD), remain controversial. Since they are known to correlate with vascular disease and vascular risk factors, we reviewed the clinical correlates of periventricular high signal (PVH) and subcortical white matter lesions (WML) in a sample of 106 patients with probable AD, excluding persons with treated vascular risk factors or symptomatic cerebrovascular and cardiovascular disease. Grade 2 PVH were seen in 26 (25%) and scattered WML were identified in 29 (18%). PHV were associated with advancing age and gait disturbance. WML were associated with gait disturbance and incontinence. Neither radiologic finding was related to dementia severity. The findings suggest that these lesions are common in patients with AD even when those with evidence of cerebrovascular disease are excluded; their presence, therefore, should not preclude a diagnosis of AD. Additionally, the data suggest that HSL on MRI may be one of many risk factors associated with functional disability in persons with probable AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology;Analysis of Variance;Brain/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Bennett, D. A.;Gilley, D. W.;Wilson, R. S.;Huckman, M. S.;Fox, J. H.",1992,Apr,,0,
5399,White matter changes: neurobehavioral manifestations of Binswanger's disease and clinical correlates in Alzheimer's disease,"Although white matter lesions (WMLs) are among the most common structural neuroimaging changes found on computed tomography and magnetic resonance imaging of older persons with dementia, their presence should not be misconstrued as proof that vascular disease is causing or contributing to the dementia. We report the results of several studies examining the neurobehavioral manifestations of persons meeting explicit operational criteria for Binswanger's disease (BD) and the clinical correlates of white matter changes in persons with autopsy-proven Alzheimer's disease (AD). The findings suggest that relative to persons with AD of comparable dementia severity, persons with BD have less profound impairments in episodic memory, more depressive symptomatology and a more variable rate of cognitive decline; among persons with AD, some WMLs are associated with incontinence and gait disturbance, but they do not appear to contribute to dementia severity.","Alzheimer Disease/ pathology/psychology/radiography;Behavior/physiology;Brain/ pathology/radiography;Cognition Disorders/pathology/psychology;Dementia, Vascular/ pathology/psychology/radiography;Humans;Magnetic Resonance Imaging;Neurologic Examination;Psychiatric Status Rating Scales;Tomography, X-Ray Computed;Urinary Incontinence","Bennett, D. A.;Gilley, D. W.;Lee, S.;Cochran, E. J.",1994,May-Aug,,0,
5400,White matter tract integrity metrics reflect the vulnerability of late-myelinating tracts in Alzheimer's disease,"Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Analysis of Variance;Diffusion Tensor Imaging;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/pathology;Myelin Sheath/ pathology;Neuropsychological Tests;Psychiatric Status Rating Scales;Semantics;White Matter/ pathology","Benitez, A.;Fieremans, E.;Jensen, J. H.;Falangola, M. F.;Tabesh, A.;Ferris, S. H.;Helpern, J. A.",2014,,10.1016/j.nicl.2013.11.001,0,
5401,White-matter lesions without lacunar infarcts in CADASIL,"To better characterize the clinical spectrum related to white-matter hyperintensities (WMH) in small vessel disease, 66 patients with WMH but without any lacunar infarct were selected out of a cohort of 248 CADASIL individuals. Characteristics of these patients were compared to those of patients with lacunar infarcts. Relationships between the normalized volume of WMH (nWMH), presence of microhemorrhages, brain parenchymal fraction (BPF). and cognitive performances were assessed. The Trail Making Test (TMT) A and B times, Mattis Dementia Rating Scale (MDRS) total score, attention subscore, verbal fluency score and delayed memory recall were significantly correlated with nWMH but not with BPF. Presence of microhemorrhages was associated with worse TMT B time and attention MDRS subscore after adjustment for WMH. All subjects had Mini-Mental Status Examination scores >/=24 and presented with no or only mild disability. These results suggest that CADASIL patients with isolated WMH can present with executive and attention deficit but not with severe disability and that additional lesions are needed to cause significant disability and/or dementia.","Adult;Aged;Brain/*pathology;CADASIL/complications/*pathology;Cognition Disorders/etiology;Cohort Studies;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/*pathology;Psychiatric Status Rating Scales;Stroke, Lacunar/pathology;Trail Making Test;Young Adult","Benisty, S.;Reyes, S.;Godin, O.;Herve, D.;Zieren, N.;Jouvent, E.;Zhu, Y.;During, M.;Dichgans, M.;Chabriat, H.",2012,,10.3233/jad-2012-111784,0,
5402,Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study,"OBJECTIVES: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. METHODS: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. RESULTS: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. CONCLUSION: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.","Aged;Aged, 80 and over;Alzheimer Disease/psychology;Basal Ganglia/pathology;Brain/*pathology;Cerebral Infarction/*pathology/*psychology;Cognition/*physiology;Dementia/etiology/psychology;Female;Humans;Leukoaraiosis/*pathology/*psychology;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Psychomotor Performance/physiology;Socioeconomic Factors","Benisty, S.;Gouw, A. A.;Porcher, R.;Madureira, S.;Hernandez, K.;Poggesi, A.;van der Flier, W. M.;Van Straaten, E. C.;Verdelho, A.;Ferro, J.;Pantoni, L.;Inzitari, D.;Barkhof, F.;Fazekas, F.;Chabriat, H.",2009,May,10.1136/jnnp.2008.160440,0,
5403,White Matter Hyperintensities Relate to Clinical Progression in Subjective Cognitive Decline,"Background and Purpose - In patients with subjective cognitive decline, we assessed whether small vessel disease was associated with clinical progression and cognitive decline. Methods - We included 334 patients with subjective cognitive decline. Follow-up was 3±2 years. Results - Fifty-three (16%) patients progressed clinically to mild cognitive impairment or dementia. White matter hyperintensities were associated with clinical progression and with annual decline on memory, attention, executive functioning, and global cognition. Microbleeds and lacunes were not associated with clinical progression or cognitive decline. Conclusions - In patients with subjective cognitive decline, patients with white matter hyperintensities are at increased risk of clinical progression and cognitive decline.",adult;Alzheimer disease;article;attention;cognitive defect;dementia;disease course;female;follow up;human;major clinical study;male;manager;medial temporal lobe;memory;mild cognitive impairment;multiinfarct dementia;nuclear magnetic resonance imaging;priority journal;white matter;white matter lesion,"Benedictus, M. R.;Van Harten, A. C.;Leeuwis, A. E.;Koene, T.;Scheltens, P.;Barkhof, F.;Prins, N. D.;Van Der Flier, W. M.",2015,,,0,
5404,"Microbleeds, Mortality, and Stroke in Alzheimer Disease: The MISTRAL Study","IMPORTANCE: Microbleeds are more prevalent in patients with Alzheimer disease (AD) compared with the general elderly population. In addition, microbleeds have been found to predict mortality in AD. OBJECTIVE: To investigate whether microbleeds in AD increase the risk for mortality, stroke (including intracerebral hemorrhage), and cardiovascular events. DESIGN, SETTING AND PARTICIPANTS: The MISTRAL (do MIcrobleeds predict STRoke in ALzheimer's disease) Study is a longitudinal cohort study within the memory clinic-based Amsterdam Dementia Cohort. We selected all patients with AD with a baseline visit between January 2, 2002, and December 16, 2009, and microbleeds (n = 111) and matched those (1:2) for age, sex, and magnetic resonance imaging scanner to 222 patients with AD without microbleeds. After a minimal follow-up of 3 years, information on all-cause mortality, stroke-related mortality, and cardiovascular mortality was obtained between November 1, 2012, and May 1, 2014. In addition, we obtained information on the occurrence of incident stroke or transient ischemic attack, cardiovascular events, and nursing home admittance. MAIN OUTCOMES AND MEASURES: Stroke-related mortality, incident stroke, and intracerebral hemorrhage. RESULTS: Patients had a mean (SD) age of 71.2 (7.8) years and 127 (42%) were female. Compared with having no microbleeds, microbleeds in lobar locations were associated with an increased risk for stroke-related mortality (hazard ratio [HR], 33.9; 95% CI, 2.5-461.7), whereas nonlobar microbleeds were associated with an increased risk for cardiovascular mortality (HR, 12.0; 95% CI, 3.2-44.7). In addition, lobar microbleeds were associated with an increased risk for incident stroke (HR, 3.8; 95% CI, 1.5-10.1) and nonlobar microbleeds with an increased risk for cardiovascular events (HR, 6.2; 95% CI, 1.5-25.0). Even higher risks for incident stroke and cardiovascular events were found in patients using antithrombotic medication. All 5 patients with an intracerebral hemorrhage had lobar microbleeds at baseline; 4 of them used antithrombotics. CONCLUSIONS AND RELEVANCE: In patients with AD, the presence of nonlobar microbleeds was associated with an increased risk for cardiovascular events and cardiovascular mortality. Patients with lobar microbleeds had an increased risk for stroke and stroke-related mortality, indicating that these patients should be treated with the utmost care.","Aged;Alzheimer Disease/epidemiology/ mortality/pathology;Cardiovascular Diseases/epidemiology/ mortality;Cerebral Hemorrhage/epidemiology/ mortality/pathology;Comorbidity;Female;Humans;Ischemic Attack, Transient/epidemiology/ mortality/pathology;Longitudinal Studies;Male;Netherlands/epidemiology;Stroke/epidemiology/ mortality/pathology","Benedictus, M. R.;Prins, N. D.;Goos, J. D.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.",2015,May,10.1001/jamaneurol.2015.14,0,
5405,Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease,"OBJECTIVE: To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD). METHODS: We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 +/- 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p </= 0.05. RESULTS: Patients were 65 +/- 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 +/- 4. Annual decline (beta[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (beta[SE]-0.50[0.25]; p </= 0.05) and parietal (beta[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline. CONCLUSIONS: Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD. KEY POINTS: * In AD, lower CBF is associated with more rapid cognitive decline. * Decreasing CBF does not reach a plateau early in AD. * PcASL-CFB has additive value to conventional structural MRI measures in AD.",0 (Spin Labels);Aged;Alzheimer Disease/ diagnostic imaging/pathology/psychology;Atrophy/pathology;Brain/ diagnostic imaging/pathology;Cerebrovascular Circulation;Disease Progression;Female;Gray Matter/diagnostic imaging/pathology;Humans;Linear Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Spin Labels;Temporal Lobe/diagnostic imaging/pathology;Time Factors;Alzheimer's disease;dementia;perfusion;prognosis;progression,"Benedictus, M. R.;Leeuwis, A. E.;Binnewijzend, M. A.;Kuijer, J. P.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.;Prins, N. D.",2017,Mar,,0,5406
5406,Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease,"OBJECTIVE: To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD). METHODS: We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 +/- 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p </= 0.05. RESULTS: Patients were 65 +/- 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 +/- 4. Annual decline (beta[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (beta[SE]-0.50[0.25]; p </= 0.05) and parietal (beta[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline. CONCLUSIONS: Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD. KEY POINTS: * In AD, lower CBF is associated with more rapid cognitive decline. * Decreasing CBF does not reach a plateau early in AD. * PcASL-CFB has additive value to conventional structural MRI measures in AD.",Alzheimer's disease;dementia;perfusion;prognosis;progression,"Benedictus, M. R.;Leeuwis, A. E.;Binnewijzend, M. A.;Kuijer, J. P.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.;Prins, N. D.",2016,Jun 22,10.1007/s00330-016-4450-z,0,
5407,Specific risk factors for microbleeds and white matter hyperintensities in Alzheimer's disease,"We investigated whether microbleeds and white matter hyperintensities (WMH) in Alzheimer's disease (AD) associate more with conventional vascular risk factors or with risk factors that reflect amyloid burden. A total of 371 patients with probable AD were included. WMH (Fazekas 2 or 3) were present in 107 (29%) patients and microbleeds were seen in 98 (26%). Patients with both microbleeds and WMH were older and presented more frequently with lacunes and multiple microbleeds than patients with microbleeds in isolation (all p < 0.05). Using multivariate regression models, we found that WMH presence showed independent associations with age, hypertension, current smoking, and lacune presence. Microbleeds were independently associated with male gender, higher blood pressure, lower cerebrospinal fluid Abeta42, and apolipoprotein E epsilon4 homozygosity. Separate analyses for microbleeds according to their location showed that these associations were driven by microbleeds in lobar locations. Our results suggest that, unlike WMH, microbleeds in AD are particularly associated with additional amyloid burden, and as such, may relate to cerebral amyloid angiopathy.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/*complications/genetics;Amyloid beta-Peptides/cerebrospinal fluid;Analysis of Variance;Apolipoprotein E4/genetics;Cerebral Hemorrhage/*etiology/genetics;Cohort Studies;Enzyme-Linked Immunosorbent Assay;Female;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/*etiology/genetics;Magnetic Resonance Imaging;Male;Peptide Fragments/cerebrospinal fluid;Retrospective Studies;Risk Factors;Alzheimer's disease;ApoE;Microbleeds;Microhemorrhage;Small vessel disease;White matter hyperintensities","Benedictus, M. R.;Goos, J. D.;Binnewijzend, M. A.;Muller, M.;Barkhof, F.;Scheltens, P.;Prins, N. D.;van der Flier, W. M.",2013,Nov,10.1016/j.neurobiolaging.2013.04.023,0,
5408,Brain volume and white matter hyperintensities as determinants of cerebral blood flow in Alzheimer's disease,"To better understand whether decreased cerebral blood flow (CBF) in patients with Alzheimer's disease (AD) reflects neurodegeneration or cerebral small vessel disease, we investigated the associations of normalized brain volume (NBV) and white matter hyperintensity (WMH) volume with CBF. We included 129 patients with AD (66 +/- 7 years, 53% female) and 61 age-matched controls (64 +/- 5 years, 43% female). CBF was measured with pseudocontinuous arterial spin labeling at 3T in the whole brain and in partial volume corrected cortical maps. When NBV and WMH were simultaneously entered in age and sex adjusted models, smaller NBV was associated with lower whole brain (Stbeta: 0.29; p < 0.01) and cortical CBF (Stbeta: 0.28; p < 0.01) in patients with AD. Larger WMH volume was also associated with lower whole brain (Stbeta: -0.22; p < 0.05) and cortical CBF (Stbeta: -0.24; p < 0.05) in AD. Additional adjustments did not change these results. In controls, neither NBV nor WMH was associated with CBF. Our results indicate that in AD, lower CBF as measured using pseudocontinuous arterial spin labeling, reflects the combined disease burden of both neurodegeneration and small vessel disease.",Aged;Alzheimer Disease/*pathology/*physiopathology;Brain/*blood supply/*pathology;*Cerebrovascular Circulation;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Organ Size;White Matter/*pathology;Alzheimer's disease;Arterial spin labeling;Cerebral blood flow;Cerebral small vessel disease;Neurodegeneration,"Benedictus, M. R.;Binnewijzend, M. A.;Kuijer, J. P.;Steenwijk, M. D.;Versteeg, A.;Vrenken, H.;Scheltens, P.;Barkhof, F.;van der Flier, W. M.;Prins, N. D.",2014,Dec,10.1016/j.neurobiolaging.2014.06.001,0,
5409,White matter is altered with parental family history of Alzheimer's disease,"Background: Brain alterations in structure and function have been identified in people with risk factors for sporadic type Alzheimer's disease (AD), suggesting that alterations can be detected decades before AD diagnosis. Although the effect of apolipoprotein E (APOE) ε4 on the brain is well-studied, less is known about the effect of family history of AD. We examined the main effects of family history and APOE ε4 on brain integrity, in addition to assessing possible additive effects of these two risk factors. Methods: Diffusion tensor imaging was performed in 136 middle-aged asymptomatic participants stratified on family history and APOE ε4. Mean diffusivity and fractional anisotropy (FA) were entered in factorial analyses to test the effect of AD risk on microstructural brain integrity. We performed a post hoc analysis of the three principal diffusivities (λ1, λ2, λ3) to provide potential additional insight on underlying tissue differences. Results: Parental family history of AD was associated with lower FA in regions of the brain known to be affected by AD, including cingulum, corpus callosum, tapetum, uncinate fasciculus, hippocampus, and adjacent white matter. Contrary to previous reports, there was no main effect of APOE ε4; however, there was an additive effect of family history and APOE ε4 in which family history-positive participants who were also APOE ε4 carriers had the lowest FA compared with the other groups. Conclusions: The data indicate that unknown risk factors contained in family history are associated with changes in microstructural brain integrity in areas of the brain known to be affected by AD. Importantly, the results provide further evidence that AD pathology might be detected before cognitive changes, perhaps decades before disease onset. © 2010 The Alzheimers Association. All rights reserved.",,"Bendlin, B. B.;Ries, M. L.;Canu, E.;Sodhi, A.;Lazar, M.;Alexander, A. L.;Carlsson, C. M.;Sager, M. A.;Asthana, S.;Johnson, S. C.",2010,September,,0,
5410,CSF T-TAU/Aβ42 predicts white matter microstructure in healthy adults at risk for alzheimer's disease,"Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ42 are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ42, total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter. © 2012 Bendlin et al.",biological marker;tau protein;adult;aged;Alzheimer disease;article;brain cortex;cerebrospinal fluid analysis;clinical article;controlled study;diffusion tensor imaging;diffusion weighted imaging;family history;female;gray matter;human;male;neurofilament;neuropsychological test;nuclear magnetic resonance imaging;protein phosphorylation;recognition;white matter,"Bendlin, B. B.;Carlsson, C. M.;Johnson, S. C.;Zetterberg, H.;Blennow, K.;Willette, A. A.;Okonkwo, O. C.;Sodhi, A.;Ries, M. L.;Birdsill, A. C.;Alexander, A. L.;Rowley, H. A.;Puglielli, L.;Asthana, S.;Sager, M. A.",2012,,,0,
5411,CSF T-Tau/Abeta42 predicts white matter microstructure in healthy adults at risk for Alzheimer's disease,"Cerebrospinal fluid (CSF) biomarkers T-Tau and Abeta(42) are linked with Alzheimer's disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Abeta(42), total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Abeta(42) were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Abeta(42) levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.",Adult;Alzheimer Disease/ diagnosis/genetics/pathology;Amyloid beta-Peptides/ cerebrospinal fluid;Analysis of Variance;Biomarkers/ cerebrospinal fluid;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/ pathology;Neuropsychological Tests;Peptide Fragments/ cerebrospinal fluid;Phosphorylation;Recognition (Psychology)/physiology;Wisconsin;tau Proteins/metabolism,"Bendlin, B. B.;Carlsson, C. M.;Johnson, S. C.;Zetterberg, H.;Blennow, K.;Willette, A. A.;Okonkwo, O. C.;Sodhi, A.;Ries, M. L.;Birdsill, A. C.;Alexander, A. L.;Rowley, H. A.;Puglielli, L.;Asthana, S.;Sager, M. A.",2012,,10.1371/journal.pone.0037720,0,
5412,[Imaging findings in autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - CADASIL - the most frequent familial stroke syndrome] Imaging Findings in Autosomal-dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) - CADASIL - das haufigste familiare Schlaganfallsyndrom,,"0 (NOTCH3 protein, human);0 (Receptor, Notch3);0 (Receptors, Notch);33X04XA5AT (Lactic Acid);N91BDP6H0X (Choline);Aged;Brain/ pathology;CADASIL/ diagnosis/genetics/pathology;Choline/metabolism;Chromosome Aberrations;DNA Mutational Analysis;Dementia, Vascular/diagnosis;Diffusion Magnetic Resonance Imaging;Female;Genes, Dominant;Humans;Image Interpretation, Computer-Assisted;Lactic Acid/metabolism;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Positron-Emission Tomography;Receptor, Notch3;Receptors, Notch/genetics;Stroke/ diagnosis/genetics/pathology;Tomography, X-Ray Computed","Bender, B.;Bornemann, A.;Reimold, M.;Ernemann, U.;Horger, M.",2012,Aug,,0,
5413,Imaging findings in autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) - CADASIL - the most frequent familial stroke syndrome,,"Aged;Brain/ pathology;CADASIL/ diagnosis/genetics/pathology;Choline/metabolism;Chromosome Aberrations;DNA Mutational Analysis;Dementia, Vascular/diagnosis;Diffusion Magnetic Resonance Imaging;Female;Genes, Dominant;Humans;Image Interpretation, Computer-Assisted;Lactic Acid/metabolism;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Positron-Emission Tomography;Receptors, Notch/genetics;Stroke/ diagnosis/genetics/pathology;Tomography, X-Ray Computed","Bender, B.;Bornemann, A.;Reimold, M.;Ernemann, U.;Horger, M.",2012,Aug,10.1055/s-0032-1318829,0,
5414,Magnetic resonance imaging of the brain and spinal cord in cerebrotendinous xanthomatosis,"This reports a 40 year old man with cerebrotendinous xanthomatosis who had bilateral cataracts, enlarged Achilles tendons, progressive dementia, gait disturbance and peripheral neuropathy. Electroencephalography, electromyography, and magnetic resonance imaging (MRI) of the brain and spine were performed. Magnetic resonance imaging revealed cerebral, cerebellar and cervical cord atrophy and white matter involvement in the cerebrum and cerebellum correlating well with the clinical findings. To date there has been one previous report of MRI of the brain in cerebrotendinous xanthomatosis and none of the spinal cord.",,"Bencze, K. S.;Vande Polder, D. R.;Prockop, L. D.",1990,1990,,0,
5415,Genetically proven cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a 3-year-old,Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has always been considered to be a middle-age-onset disease. Diagnosis is confirmed by genetic testing and the finding of the Notch3 mutation or by skin biopsy. Imaging plays a pivotal and crucial role in confirming this diagnosis by identifying white matter changes early in the disease. This can be useful in screening symptomatic patients with a family history of the disease. CADASIL cases have been reported recently in children. We report our experience with CADASIL in a 3-year-old boy. © 2013 Springer-Verlag Berlin Heidelberg.,,"Benabu, Y.;Beland, M.;Ferguson, N.;Maranda, B.;Boucher, R. M.",2013,September,,0,
5416,Gait Measures as Predictors of Poststroke Cognitive Function: Evidence from the TABASCO Study,"Background and Purpose-Patients with stroke are at risk for developing cognitive impairment. We tested whether the assessment of balance and gait can enhance the prediction of long-term cognitive outcome in stroke survivors. Methods-Participants were patients with first-ever, mild-moderate ischemic stroke or transient ischemic attack from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study, a large prospective cohort study, who underwent 3-T MRI and were followed for ≥2 years using neurological, neuropsychological, and mobility examinations 6, 12, and 24 months after the index event. Results-Data were available for 298 patients (age: 66.7±9.6 years). Forty-six participants (15.4%) developed cognitive decline (CD) over the 2 years of follow-up. The CD group and cognitively intact group did not differ in their neurological deficits or in their infarct volume or location. Nonetheless, 6 months after stroke, the Timed Up and Go test took longer in those who later developed CD (P<0.001). Additionally, the CD group also had lower Berg Balance Scale scores (P<0.001), slower gait (P<0.001), and fewer correct answers during dual-task walking (P=0.006). Separate analyses of the patients with transient ischemic attack revealed similar results. Multivariate regression analysis showed that Timed Up and Go times >12 s at 6 months after stroke/transient ischemic attack was a significant independent risk marker of CD 24 months after stroke (odds ratio=6.07, 95% confidence interval: 1.36-27.15). Conclusions-These results suggest that measures of balance and gait are significant risk markers of cognitive status 2 years after stroke. Relatively simple, performance-based tests of mobility may enhance the identification of stroke/transient ischemic attack survivors who have an increased risk of developing CD.",NCT01926691;aged;article;Berg Balance Scale;brain infarction size;brain ischemia;cognition;cohort analysis;female;gait;human;major clinical study;male;mental deterioration;mobilization;National Institutes of Health Stroke Scale;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;prediction;priority journal;prospective study;Timed Up and Go test;transient ischemic attack,"Ben Assayag, E.;Shenhar-Tsarfaty, S.;Korczyn, A. D.;Kliper, E.;Hallevi, H.;Shopin, L.;Auriel, E.;Giladi, N.;Mike, A.;Halevy, A.;Weiss, A.;Mirelman, A.;Bornstein, N. M.;Hausdorff, J. M.",2015,,,0,
5417,Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline,"BACKGROUND AND PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. METHODS: The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. RESULTS: At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. CONCLUSIONS: T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691.","Aged;Brain/diagnostic imaging/pathology;Cerebral Cortex/diagnostic imaging/pathology;Cognitive Dysfunction/diagnostic imaging/epidemiology/etiology/ psychology;Cohort Studies;Comorbidity;Dementia/diagnostic imaging/epidemiology/etiology/ psychology;Diabetes Mellitus, Type 2/ epidemiology;Executive Function;Female;Hippocampus/diagnostic imaging/pathology;Humans;Israel/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Motor Skills;Neuropsychological Tests;Organ Size;Prospective Studies;Renal Insufficiency, Chronic/ epidemiology;Risk Factors;Stroke/complications/diagnostic imaging/epidemiology/ psychology;White Matter/diagnostic imaging/pathology;cognitive dysfunction;dementia;diabetes mellitus;ischemic attack, transient;stroke","Ben Assayag, E.;Eldor, R.;Korczyn, A. D.;Kliper, E.;Shenhar-Tsarfaty, S.;Tene, O.;Molad, J.;Shapira, I.;Berliner, S.;Volfson, V.;Shopin, L.;Strauss, Y.;Hallevi, H.;Bornstein, N. M.;Auriel, E.",2017,Sep,,0,
5418,An easy way to increase confidence in beta-amyloid PET evaluation,"BACKGROUND: In patients with brain atrophy, it is not easy to distinguish pathologic uptake of flutemetamol (FMM) in the gray matter from nonspecific, physiologic uptake in the white matter. In this paper we suggest an easy image processing method. MATERIAL AND METHODS: The proof-of-concept study involved three patients with mild cognitive impairment and different graphical findings at FMM-PET. Two-phase FMM-PET was acquired; the early phase represented the perfusion of gray matter, while the late phase depicted the white matter and beta-amyloid load in the gray matter. The border of the gray matter was easily extracted from the early-phase images using thresholding and the isocontour ""Edges"" color table. The late phase was registered with the edge images of the early phase and displayed using alpha-blending. RESULTS: Early- A nd late-phase image fusion displayed with appropriate color tables is presented in three different cases to illustrate the added value of the suggested approach. CONCLUSIONS: Composite late-phase images with enhanced gray matter borders strongly facilitate assessment of beta-amyloid presence in the gray matter. This is especially helpful in patients with brain atrophy.",amyloid beta protein;flutemetamol f 18;adult;Alzheimer disease;article;brain atrophy;brain perfusion;case report;color;female;gray matter;human;image processing;male;middle aged;mild cognitive impairment;neuroimaging;PET-CT scanner;positron emission tomography;white matter;vizamyl;Siemens Biograph 40 TrueV HD,"Belohlavek, O.;Jaruskova, M.",2017,,10.5603/nmr.2017.0019,0,
5419,Biomarkers of Cognitive Training Effects in Aging,"An increasing number of studies have relied on brain imaging to assess the effects of cognitive training in healthy aging populations and in persons with early Alzheimer's disease or mild cognitive impairment (MCI). At the structural level, cognitive training in healthy aging individuals has been associated with increased brain volume, cortical thickness, and density and coherence of white matter tracts. At the functional level, task-related brain activation (using fMRI and PET) and fluorodeoxyglucose positron emission tomography (FDG-PET) were found to be sensitive to the effects of training. In persons with MCI, cognitive training increased brain metabolism and task-related brain activation, whereas healthy older adults showed patterns of increased and decreased activation. Further studies are required to generalize these findings to larger groups and to investigate more diverse training protocols. Research will also need to address important methodological issues regarding the use of biomarkers in cognitive aging, including reliability, clinical validity, and relevance to the pathophysiological process.",,"Belleville, S.;Bherer, L.",2012,Jun,10.1007/s13670-012-0014-5,0,
5420,Enhanced motor cortex facilitation in patients with vascular cognitive impairment-no dementia,"Data on Transcranial Magnetic Stimulation (TMS) derived measures of cortical excitability and intracortical circuits in age-related white matter changes are scarce. We aimed to assess early changes of motor cortex excitability in nondemented elderly patients with subcortical ischemic vascular disease (SVD). Ten SVD elderly and ten age-matched controls underwent paired-pulse TMS for the analysis of intracortical inhibition (ICI) and facilitation (ICF). All subjects performed neuropsychological assessment and brain magnetic resonance imaging. SVD patients showed abnormal executive control function. No statistically significant differences were found for resting motor threshold, cortical silent period between SVD patients and controls or between the two hemispheres, in patients. A significant enhancement of mean ICF was observed in SVD patients. This study provides the first evidence of functional changes in intracortical excitatory neuronal circuits in patients with SVD and clinical features of vascular cognitive impairment-no dementia. Further studies are required to evaluate whether the observed change of ICF might predict cognitive and/or motor impairment in a population at risk for subcortical vascular dementia.","Age Factors;Aged;Brain Ischemia/physiopathology/psychology;Cerebrovascular Disorders/complications/ physiopathology/ psychology;Cognition Disorders/etiology/ physiopathology/ psychology;Demography;Diagnostic and Statistical Manual of Mental Disorders;Evoked Potentials, Motor/physiology;Female;Functional Laterality;Humans;Magnetic Resonance Imaging;Male;Motor Cortex/ physiology;Sex Factors;Stroke/physiopathology;Transcranial Magnetic Stimulation","Bella, R.;Ferri, R.;Pennisi, M.;Cantone, M.;Lanza, G.;Malaguarnera, G.;Spampinato, C.;Giordano, D.;Alagona, G.;Pennisi, G.",2011,Oct 10,10.1016/j.neulet.2011.08.022,0,
5421,"HIV encephalitis, proviral load and dementia in drug users and homosexuals with AIDS. Effect of neocortical involvement","In this consecutive autopsy study, the pathological evidence of HIV encephalitis, which included the presence of giant cells and/or HIV p24 immunopositivity, was found more frequently in drug users (25 of 45; 56%) than in homosexual men (6 of 35; 17%) with AIDS (P < 0.01). Productive infection, as shown by HIV p24 positivity, was found in frontal lobe white matter in 29 of the 31 HIV encephalitis cases, but was also present in grey matter in 50% of the HIV encephalitis cases. Immunopositivity was confined to microglia, monocytes and most but not all giant cells. HIV-1 proviral load was determined by quantitative PCR in 65 of the 80 cases (separately in grey and white matter in 49 of these), and correlated well with the presence of HIV encephalitis (P < 0.001). Twenty-five patients with AIDS (13 male homosexuals, 12 drug users) showed no HIV encephalitis, opportunistic infection or cerebral lymphoma, while 18 (2 male homosexuals, 16 drug users) showed pure HIV encephalitis. Cognitive function had been assessed prospectively in this cohort and graded as normal or mildly, moderately or severely impaired. Because opportunistic infections and lymphomas of the brain may also lead to dementia, patients found to have these conditions at autopsy were excluded from the final analysis of the cases with dementia, so that the precise correlation between cognitive impairment and pure HIV encephalitis could be determined in this cohort without possible confounding variables. Fourteen of 18 patients with pure HIV encephalitis had shown cognitive impairment. Severe dementia correlated better with pure HIV encephalitis in cases in which grey matter involvement was present (7 out of 9) than in those in which only white matter was involved (2 out of 9) (P < 0.05), although milder degrees of cognitive impairment had been present in a further 5 HIV encephalitis cases. No correlation was found between zidovudine therapy and the degree of cognitive impairment. Systemic and cerebral opportunistic infections and lymphoma showed a negative association with HIV encephalitis, being more common in homosexuals than in drug users, despite comparable CD4 counts in the two groups. These findings suggest that neocortical productive HIV infection is a significant factor in AIDS-related dementia, although this may reflect merely a higher overall viral burden in the brain.","AIDS Dementia Complex/*pathology/virology;Autopsy;Cognition Disorders/etiology/pathology/virology;Cohort Studies;Encephalitis, Viral/*pathology/virology;Female;HIV Core Protein p24/*analysis;HIV Infections/*complications/pathology/virology;HIV Seropositivity/pathology/virology;HIV-1/*isolation & purification;*Homosexuality, Male;Humans;Magnetic Resonance Imaging;Male;Neocortex/*pathology/virology;Proviruses/*isolation & purification;*Substance Abuse, Intravenous","Bell, J. E.;Brettle, R. P.;Chiswick, A.;Simmonds, P.",1998,Nov,,0,
5422,Factors influencing accuracy of cortical thickness in the diagnosis of Alzheimer's disease,"There is great value to use of structural neuroimaging in the assessment of Alzheimer's disease (AD). However, to date, predictive value of structural imaging tend to range between 80% and 90% in accuracy and it is unclear why this is the case given that structural imaging should parallel the pathologic processes of AD. There is a possibility that clinical misdiagnosis relative to the gold standard pathologic diagnosis and/or additional brain pathologies are confounding factors contributing to reduced structural imaging classification accuracy. We examined potential factors contributing to misclassification of individuals with clinically diagnosed AD purely from cortical thickness measures. Correctly classified and incorrectly classified groups were compared across a range of demographic, biological, and neuropsychological data including cerebrospinal fluid biomarkers, amyloid imaging, white matter hyperintensity (WMH) volume, cognitive, and genetic factors. Individual subject analyses suggested that at least a portion of the control individuals misclassified as AD from structural imaging additionally harbor substantial AD biomarker pathology and risk, yet are relatively resistant to cognitive symptoms, likely due to ""cognitive reserve,"" and therefore clinically unimpaired. In contrast, certain clinical control individuals misclassified as AD from cortical thickness had increased WMH volume relative to other controls in the sample, suggesting that vascular conditions may contribute to classification accuracy from cortical thickness measures. These results provide examples of factors that contribute to the accuracy of structural imaging in predicting a clinical diagnosis of AD, and provide important information about considerations for future work aimed at optimizing structural based diagnostic classifiers for AD.",Alzheimer's disease;cortical thickness;magnetic resonance imaging;support vector machines;white matter hyperintensity,"Belathur Suresh, M.;Fischl, B.;Salat, D. H.;Alzheimer's Disease Neuroimaging, Initiative",2017,Dec 21,,0,
5423,The value of magnetic resonance imaging in the early diagnosis of Creutzfeldt-Jakob disease - own experience,"BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare progressive neurodegenerative disorder, caused by the deposition of the pathological isoform of prion protein PrPsc in the central nervous system. The classic triad of symptoms consists of: rapidly progressive dementia, myoclonus and typical electroencephalographic findings (intermittent rhythmic delta activity and periodic sharp wave complexes). Detection of 14-3-3 protein in the cerebrospinal fluid plays an important diagnostic role as well. Magnetic resonance (MR) images of the brain have been recently incorporated into the diagnostic criteria of sporadic Creutzfeldt-Jakob disease. CASE REPORT: MR examinations were performed in a 65-year-old man and a 54-year-old woman with delusional disorder and cognitive dysfunction, respectively. Diffusion restriction (hyperintense signal in DWI) was shown in the cortex of the left parietal and occipital lobe in the first patient and symmetrically in the cortex of both cerebral hemispheres except for precentral gyri in the second one. In both cases, the first examinations were misread, with the suspicion of ischemic infarcts as the first differential diagnosis. Consultations and subsequent MR examinations in which lesions in subcortical nuclei appeared allowed for a diagnosis of probable CJD. In the first case it was confirmed by clinical picture, EEG and finally - autopsy. In the second case, EEG was not typical for CJD but the clinical course of the disease confirmed that diagnosis. CONCLUSIONS: The authors present the cases of two patients with characteristic MR images that allowed early diagnosis of probable Creutzfeldt-Jakob disease before the characteristic clinical picture appeared. Early diagnosis is nowadays important for the prevention of disease transmission and in the future - hopefully - for early treatment.",,"Bekiesinska-Figatowska, M.;Kuczynska-Zardzewialy, A.;Pomianowska, B.;Kajdana, K.;Szpak, G. M.;Iwanowska, B.;Madzik, J.",2012,Jan,,0,
5424,Distinct white matter injury associated with medial temporal lobe atrophy in Alzheimer's versus semantic dementia,"This study aims at further understanding the distinct vulnerability of brain networks in Alzheimer's disease (AD) versus semantic dementia (SD) investigating the white matter injury associated with medial temporal lobe (MTL) atrophy in both conditions. Twenty-six AD patients, twenty-one SD patients, and thirty-nine controls underwent a high-resolution T1-MRI scan allowing to obtain maps of grey matter volume and white matter density. A statistical conjunction approach was used to identify MTL regions showing grey matter atrophy in both patient groups. The relationship between this common grey matter atrophy and white matter density maps was then assessed within each patient group. Patterns of grey matter atrophy were distinct in AD and SD but included a common region in the MTL, encompassing the hippocampus and amygdala. This common atrophy was associated with alterations in different white matter areas in AD versus SD, mainly including the cingulum and corpus callosum in AD, while restricted to the temporal lobe - essentially the uncinate and inferior longitudinal fasciculi - in SD. Complementary analyses revealed that these relationships remained significant when controlling for global atrophy or disease severity. Overall, this study provides the first evidence that atrophy of the same MTL region is related to damage in distinct white matter fibers in AD and SD. These different patterns emphasize the vulnerability of distinct brain networks related to the MTL in these two disorders, which might underlie the discrepancy in their symptoms. These results further suggest differences between AD and SD in the neuropathological processes occurring in the MTL. Hum Brain Mapp 38:1791-1800, 2017. (c) 2017 Wiley Periodicals, Inc.",Alzheimer's disease;hippocampus;medial temporal lobe;primary progressive aphasia;semantic dementia;white matter,"Bejanin, A.;Desgranges, B.;La Joie, R.;Landeau, B.;Perrotin, A.;Mezenge, F.;Belliard, S.;de La Sayette, V.;Eustache, F.;Chetelat, G.",2017,Apr,,0,
5425,"Clinical presentation, etiology, and long-term prognosis in patients with nontraumatic convexal subarachnoid hemorrhage","BACKGROUND AND PURPOSE-: Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. METHODS-: For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. RESULTS-: The 24 patients with cSAH had a mean age of 70 years (range, 37-88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3-6), including 5 deaths. We did not observe recurrent cSAH. CONCLUSIONS-: Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis. © 2011 American Heart Association, Inc.",,"Beitzke, M.;Gattringer, T.;Enzinger, C.;Wagner, G.;Niederkorn, K.;Fazekas, F.",2011,November,,0,
5426,Strategic subcortical hyperintensities in cholinergic pathways and executive function decline in treated Alzheimer patients,"OBJECTIVE: To investigate changes in cognition, function, and behavior after 1 year in patients with Alzheimer disease being treated with cholinesterase inhibitors, in relation to the presence or absence of subcortical hyperintensities involving the cholinergic pathways. DESIGN: One-year prospective cohort study. SETTING: Memory Clinic, Sunnybrook Health Sciences Centre, University of Toronto. Patients Ninety patients with possible/probable Alzheimer disease who were being treated with cholinesterase inhibitors at baseline. INTERVENTIONS: Yearly standardized neuropsychological testing and brain magnetic resonance imaging (MRI). The Cholinergic Pathways Hyperintensities Scale (CHIPS) was applied to baseline MRIs to rate the severity of subcortical hyperintensities in cholinergic pathways. The consensus-derived Age-Related White Matter Changes (ARWMC) Rating Scale was used as a general measure of white matter disease burden. MAIN OUTCOME MEASURES: Tests of global cognition, function, and behavior and specific cognitive and functional domains. RESULTS: Patients in the low CHIPS group were equivalent to those in the high CHIPS group with regard to baseline demographic characteristics, cognitive severity, and vascular risk factors. After covarying age and education, no differences were found after 1 year in overall cognition, function, and behavior or on memory, language, and visuospatial tasks. Patients in the high CHIPS group showed improvement on executive function and working memory tasks compared with those in the low CHIPS group. For the ARWMC scale, groups with and without white matter abnormalities were equivalent on baseline demographics and in cognitive, functional, and behavioral outcomes. CONCLUSION: Cerebrovascular compromise of the cholinergic pathways may be a factor that contributes more selectively than does total white matter lesion burden to response to cholinergic therapy in Alzheimer disease, particularly on frontal/executive tasks.","Aged;Aged, 80 and over;Alzheimer Disease/drug therapy/pathology/physiopathology;Brain Mapping;Chi-Square Distribution;Cholinesterase Inhibitors/ therapeutic use;Cognition Disorders/ drug therapy/etiology;Cohort Studies;Female;Humans;Likelihood Functions;Magnetic Resonance Imaging/methods;Male;Mental Status Schedule;Multivariate Analysis;Neuropsychological Tests/statistics & numerical data;Problem Solving/ drug effects;Receptors, Cholinergic/ metabolism","Behl, P.;Bocti, C.;Swartz, R. H.;Gao, F.;Sahlas, D. J.;Lanctot, K. L.;Streiner, D. L.;Black, S. E.",2007,Feb,10.1001/archneur.64.2.266,0,
5427,Histogram-Based Feature Extraction from Individual Gray Matter Similarity-Matrix for Alzheimer's Disease Classification,"Automatic computer-aided diagnosis (CAD) systems have been widely used in classification of patients who suffer from Alzheimer's disease (AD). This paper presents an automatic CAD system based on histogram feature extraction from single-subject gray matter similarity-matrix for classifying the AD patients from healthy controls (HC) using structural magnetic resonance imaging (MRI) data. The proposed CAD system is composed of five stages. In the first stage, segmentation is employed to perform pre-processing on the MRI images, and segment into gray matter, white matter, and cerebrospinal fluid using the voxel-based morphometric toolbox procedure. In the second stage, gray matter MRI scans are used to construct similarity-matrices. In the third stage, a novel statistical feature-generation process is proposed, utilizing the histogram of the individual similarity-matrix to represent statistical patterns of the respective similarity-matrices of different size and order into fixed-size feature-vectors. In the fourth stage, we propose to combine MRI measures with a neuropsychological test, the Functional Assessment Questionnaire (FAQ), to improve the classification accuracy. Finally, the classification is performed using a support vector machine and evaluated with the 10-fold cross-validation strategy. We evaluated the proposed method on 99 AD and 102 HC subjects from the J-ADNI. The proposed CAD system yields an 84.07% classification accuracy using MRI measures and 97.01% for combining MRI measures with FAQ scores, respectively. The experimental results indicate that the performance of the proposed system is competitive with respect to state-of-the-art techniques reported in the literature.",Alzheimer's disease;Fisher criterion;histogram;individual gray matter;similarity-matrix,"Beheshti, I.;Maikusa, N.;Matsuda, H.;Demirel, H.;Anbarjafari, G.;Japanese-Alzheimer's Disease Neuroimaging, Initiative",2017,,,0,
5428,White matter volume and cognitive dysfunction in early Huntington's disease,Background: Structural abnormalities of the striatum and cognitive impairments have consistently been shown in patients with Huntington's disease (HD). Fewer studies have examined other cerebral structures in early,,"Beglinger, L. J.;Nopoulos, P. C.;Jorge, R. E.;Langbehn, D. R.;Mikos, A. E.;Moser, D. J.;Duff, K.;Robinson, R. G.;Paulsen, J. S.",2005,June,,0,
5429,Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's disease,"BACKGROUND: To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. RESULTS: JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). CONCLUSIONS: JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/ epidemiology;Brain/ pathology;Case-Control Studies;Female;Humans;Jugular Veins/ pathology;Male;Middle Aged;Mild Cognitive Impairment/ diagnosis/ epidemiology;Organ Size;Taiwan/epidemiology","Beggs, C.;Chung, C. P.;Bergsland, N.;Wang, P. N.;Shepherd, S.;Cheng, C. Y.;Dwyer, M. G.;Hu, H. H.;Zivadinov, R.",2013,,10.1186/1471-2377-13-157,0,
5430,Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3T,"Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression; therefore, there has been significant clinical interest in studying hippocampal neurochemistry. However, the hippocampus is a challenging region to study using <sup>1</sup>H MRS, hence the use of MRS for clinical research in this region has been limited. Our goal was therefore to investigate the feasibility of obtaining high-quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter-session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consecutive sessions using a standard clinical 3T MR scanner. Neurochemical profiles were obtained with a short-echo (T<inf>E</inf>=28ms) semi-LASER localization sequence from a relatively small (~4mL) voxel that covered about 62% of the hippocampal volume as calculated from segmentation of T<inf>1</inf>-weighted images. Voxel composition was highly reproducible between sessions, with test-retest coefficients of variation (CVs) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal-to-noise ratio (~54 based on the N-acetylaspartate (NAA) methyl peak in non-apodized spectra) and linewidths (~9Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo-inositol and glutamate with high scan-rescan reproducibility (CV≤6%) and quantification precision (Cramér-Rao lower bound, CRLB<9%). Four other metabolites, including glutathione and glucose, were quantified with scan-rescan CV below 20%. Therefore, the highly optimized, short-echo semi-LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between-session variation in metabolite concentrations, as well as CRLB, was lower than the between-subject variation of the concentrations for most metabolites, indicating that the method has the sensitivity to detect inter-individual differences in the healthy brain.",,"Bednařík, P.;Moheet, A.;Deelchand, D. K.;Emir, U. E.;Eberly, L. E.;Bareš, M.;Seaquist, E. R.;Öz, G.",2015,1,,0,
5431,Longitudinal noninvasive magnetic resonance imaging of brain microhemorrhages in BACE inhibitor-treated APP transgenic mice,"Currently, several immunotherapies and BACE (Beta Site APP Cleaving Enzyme) inhibitor approaches are being tested in the clinic for the treatment of Alzheimer's disease. A crucial mechanism-related safety concern is the exacerbation of microhemorrhages, which are already present in the majority of Alzheimer patients. To investigate potential safety liabilities of long-term BACE inhibitor therapy, we used aged amyloid precursor protein (APP) transgenic mice (APP23), which robustly develop cerebral amyloid angiopathy. T2*-weighted magnetic resonance imaging (MRI), a translational method applicable in preclinical and clinical studies, was used for the detection of microhemorrhages throughout the entire brain, with subsequent histological validation. Three-dimensional reconstruction based on in vivo MRI and serial Perls' stained sections demonstrated a one-to-one matching of the lesions thus allowing for their histopathological characterization. MRI detected small Perls' positive areas with a high spatial resolution. Our data demonstrate that volumetric assessment by noninvasive MRI is well suited to monitor cerebral microhemorrhages in vivo. Furthermore, 3 months treatment of aged APP23 with the potent BACE-inhibitor NB-360 did not exacerbate microhemorrhages in contrast to Abeta-antibody beta1. These results substantiate the safe use of BACE inhibitors regarding microhemorrhages in long-term clinical studies for the treatment of Alzheimer's disease.",App23;Alzheimer's disease (AD);Bace;Cerebral amyloid angiopathy (CAA);Inhibitor;Magnetic resonance imaging (MRI);Microbleeding;Microhemorrhage,"Beckmann, N.;Doelemeyer, A.;Zurbruegg, S.;Bigot, K.;Theil, D.;Frieauff, W.;Kolly, C.;Moulin, P.;Neddermann, D.;Kreutzer, R.;Perrot, L.;Brzak, I.;Jacobson, L. H.;Staufenbiel, M.;Neumann, U.;Shimshek, D. R.",2016,Sep,10.1016/j.neurobiolaging.2016.05.009,0,
5432,"A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series","Mutations in the progranulin gene (GRN) are a major cause of frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) but the distinguishing clinical and anatomical features of this subgroup remain unclear. In a large UK cohort we found five different frameshift and premature termination mutations likely to be causative of FTLD in 25 affected family members. A previously described 4-bp insertion mutation in GRN exon 2 comprised the majority of cases in our cohort (20/25), with four novel mutations being identified in the other five affected members. Additional novel missense changes were discovered, of uncertain pathogenicity, but deletion of the entire gene was not detected. The patient collection was investigated by a single tertiary referral centre and is enriched for familial early onset FTLD with a high proportion of patients undergoing neuropsychological testing, MRI and eventual neuropathological diagnosis. Age at onset was variable, but four mutation carriers presented in their 40s and when analysed as a group, the mean age at onset of disease in GRN mutation carriers was later than tau gene (MAPT) mutation carriers and duration of disease was shorter when compared with both MAPT and FTLD-U without mutation. The most common clinical presentation seen in GRN mutation carriers was behavioural variant FTLD with apathy as the dominant feature. However, many patients had language output impairment that was either a progressive non-fluent aphasia or decreased speech output consistent with a dynamic aphasia. Neurological and neuropsychological examination also suggests that parietal lobe dysfunction is a characteristic feature of GRN mutation and differentiates this group from other patients with FTLD. MR imaging showed evidence of strikingly asymmetrical atrophy with the frontal, temporal and parietal lobes all affected. Both right- and left-sided predominant atrophy was seen even within the same family. As a group, the GRN carriers showed more asymmetry than in other FTLD groups. All pathologically investigated cases showed extensive type 3 TDP-43-positive pathology, including frequent neuronal cytoplasmic inclusions, dystrophic neurites in both grey and white matter and also neuronal intranuclear inclusions. Finally, we confirmed a modifying effect of APOE-E4 genotype on clinical phenotype with a later onset in the GRN carriers suggesting that this gene has distinct phenotypic effects in different neurodegenerative diseases. © 2008 The Author(s).",,"Beck, J.;Rohrer, J. D.;Campbell, T.;Isaacs, A.;Morrison, K. E.;Goodall, E. F.;Warrington, E. K.;Stevens, J.;Revesz, T.;Holton, J.;Al-Sarraj, S.;King, A.;Scahill, R.;Warren, J. D.;Fox, N. C.;Rossor, M. N.;Collinge, J.;Mead, S.",2008,March,,0,
5433,Dementia associated with hyperphosphatemic tumoral calcinosis,"Hyperphosphatemic tumoral calcinosis (HTC) is a rare inherited metabolic disorder manifested by pararticular calcification and hyperphosphatemia, caused by an elevated renal phosphate reabsorption threshold and elevated serum 1,25-dihydroxyvitamin D levels. The disorder usually affects African-American subjects, but has also been described in Caucasians and Hispanics. Vascular calcifications and angloid streaks have been reported to be associated with the disorder: however, dementia has not been previously reported. Our medical center has followed two African-American siblings, with HTC for over 30 years, who have developed dementia at 56 years and 67 years of age. Neither man has been hypertensive, however, magnetic resonance imaging (MRI) scans in both cases revealed multiple periventricular infarcts, suggestive of infarcts caused by vascular calcification in the central nervous system. These two brothers with HTC suggest that periventricular infarcts with dementia may be a long term complication of this disorder.",,"Beck, D. A.;Gray, L.;Lyles, K. W.",1998,June,,0,
5434,Tapping linked to function and structure in premanifest and symptomatic Huntington disease,"OBJECTIVE: Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy. METHODS: A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded. RESULTS: Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes. CONCLUSION: Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study.","Adult;Age of Onset;Atrophy;Biomechanical Phenomena;Brain/*pathology;Cross-Sectional Studies;Dna;Disease Progression;Female;*Hand;Humans;Huntington Disease/diagnosis/genetics/*pathology/*physiopathology;Magnetic Resonance Imaging;Male;Middle Aged;*Motor Activity;Neuropsychological Tests;*Psychomotor Performance;Repetitive Sequences, Nucleic Acid;Severity of Illness Index","Bechtel, N.;Scahill, R. I.;Rosas, H. D.;Acharya, T.;van den Bogaard, S. J.;Jauffret, C.;Say, M. J.;Sturrock, A.;Johnson, H.;Onorato, C. E.;Salat, D. H.;Durr, A.;Leavitt, B. R.;Roos, R. A.;Landwehrmeyer, G. B.;Langbehn, D. R.;Stout, J. C.;Tabrizi, S. J.;Reilmann, R.",2010,Dec 14,10.1212/WNL.0b013e3182020123,0,
5435,The relationship between hippocampal volume and static postural sway: results from the GAIT study,"The role of the hippocampus in postural control, in particular in maintaining upright stance, has not been fully examined in normal aging. This study aims to examine the association of postural sway with hippocampal volume while maintaining upright stance in healthy older individuals. Seventy healthy individuals (mean age 69.7 +/- 3.4 years; 41.4 % women) were recruited in this study based on cross-sectional design. Hippocampal volume (quantified from a three-dimensional T1-weighted MRI using semi-automated software), three center of pressure (COP) motion parameters (sway area, path length of anterior-posterior (AP) and medial-lateral (ML) displacement) while maintaining upright stance (eyes open and closed), and the relative difference between open and closed eye conditions were used as outcome measures. Age, sex, body mass index, lower limb proprioception, distance vision, 15-item geriatric depression scale score, total cranial volume, and white matter abnormalities were used as covariates. The sway area decreased from open to closed eye condition but this variation was non-significant (P = 0.244), whereas path length of AP and ML displacement increased significantly (P < 0.003). Increase in sway area from open to closed eyes was associated with greater hippocampal volume (beta -18.21; P = 0.044), and a trend for an association of increase in path length of AP displacement (P = 0.075 for open eyes and P = 0.071 for closed eyes) with greater hippocampal volume was reported. The hippocampus is involved in upright postural control in normal aging, such that an increase in sway area of COP motion from open to closed eyes is associated with greater hippocampal volume in healthy older adults.","Aged;Aging/ physiology;Alzheimer Disease/ diagnosis/physiopathology;Cross-Sectional Studies;Female;Gait/ physiology;Hippocampus/ anatomy & histology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Organ Size;Postural Balance/ physiology;Proprioception/ physiology;Reference Values;Hippocampus;Motor control;Older adults;Postural sway;Posture;financially supported by the French Ministry of Health (Projet Hospitalier de;Recherche Clinique national n2009-A00533-54).","Beauchet, O.;Barden, J.;Liu-Ambrose, T.;Chester, V. L.;Szturm, T.;Allali, G.",2016,Feb,,0,
5436,Association of Motoric Cognitive Risk Syndrome With Brain Volumes: Results From the GAIT Study,"BACKGROUND: The ""motoric cognitive risk"" (MCR) syndrome is a newly reported predementia syndrome combining cognitive complaint and slow gait speed. We hypothesized that individuals with MCR syndrome would have lower brain volumes compared with non-MCR individuals. This study aims (i) to compare the cognitive profile of nondemented older community-dwellers with and without MCR syndrome and (ii) to examine association of global and regional brain volumes with MCR syndrome. METHODS: A total of 171 individuals (28 MCR and 143 non-MCR) were included in this cross-sectional study. Total white matter abnormalities, total white matter, total cortical and subcortical gray matters, hippocampus, motor cortex, premotor cortex, and prefrontal cortex were examined. Brain volumes were quantified from a three-dimensional T1-weighted magnetic resonance imaging using semi-automated software. Age, gender, education level, number of drugs taken daily, use of psychoactive drugs, and cognitive profile were also measured. RESULTS: The distribution of cognitively healthy individuals and those with mild cognitive impairment was not different in participants with and without MCR. Multiple logistic regression models showed that smaller volumes of total gray matter (p = .016), total cortical gray matter (p = .010), premotor cortex (p = .018), prefrontal cortex (p = .026), and dorsolateral segment of prefrontal cortex (p = .032) were associated with MCR status. The premotor cortex presented the highest mean difference for brain regional volume between MCR and non-MCR participants (p = .03). CONCLUSIONS: The findings revealed similar cognitive profile in MCR and non-MCR participants, and MCR-related smaller global and regional gray matter volumes involving premotor and prefrontal cortices, suggesting that the MCR syndrome may predict cortical neurodegenerative dementia more than subcortical dementia.","Aged;Brain/ pathology;Cognition Disorders/epidemiology/ pathology;Cross-Sectional Studies;Dementia/epidemiology/ pathology;Female;France/epidemiology;Gait;Gray Matter/pathology;Hospitals, University;Humans;Incidence;Independent Living;Magnetic Resonance Imaging;Male;Neuropsychological Tests;Prevalence;Risk Factors;Surveys and Questionnaires;Syndrome;Cognitive disorders;Gait disorders;Mri;Motor control","Beauchet, O.;Allali, G.;Annweiler, C.;Verghese, J.",2016,Aug,,0,5437
5437,Association of Motoric Cognitive Risk Syndrome With Brain Volumes: Results From the GAIT Study,"BACKGROUND: The ""motoric cognitive risk"" (MCR) syndrome is a newly reported predementia syndrome combining cognitive complaint and slow gait speed. We hypothesized that individuals with MCR syndrome would have lower brain volumes compared with non-MCR individuals. This study aims (i) to compare the cognitive profile of nondemented older community-dwellers with and without MCR syndrome and (ii) to examine association of global and regional brain volumes with MCR syndrome. METHODS: A total of 171 individuals (28 MCR and 143 non-MCR) were included in this cross-sectional study. Total white matter abnormalities, total white matter, total cortical and subcortical gray matters, hippocampus, motor cortex, premotor cortex, and prefrontal cortex were examined. Brain volumes were quantified from a three-dimensional T1-weighted magnetic resonance imaging using semi-automated software. Age, gender, education level, number of drugs taken daily, use of psychoactive drugs, and cognitive profile were also measured. RESULTS: The distribution of cognitively healthy individuals and those with mild cognitive impairment was not different in participants with and without MCR. Multiple logistic regression models showed that smaller volumes of total gray matter (p = .016), total cortical gray matter (p = .010), premotor cortex (p = .018), prefrontal cortex (p = .026), and dorsolateral segment of prefrontal cortex (p = .032) were associated with MCR status. The premotor cortex presented the highest mean difference for brain regional volume between MCR and non-MCR participants (p = .03). CONCLUSIONS: The findings revealed similar cognitive profile in MCR and non-MCR participants, and MCR-related smaller global and regional gray matter volumes involving premotor and prefrontal cortices, suggesting that the MCR syndrome may predict cortical neurodegenerative dementia more than subcortical dementia.",,"Beauchet, O.;Allali, G.;Annweiler, C.;Verghese, J.",2016,Mar 4,10.1093/gerona/glw012,0,
5438,Ventricular enlargement and caudate hyperdensity in elderly depressives,"Twenty-five elderly patients (mean age 73 years, range 61-88 years) with major depression underwent cranial computed tomography (CT). The findings were compared with healthy age- and sex-matched controls. The radiodensity of the left and right heads of the caudate was significantly higher in the depressed patients (p less than 0.05). The third ventricle was significantly enlarged (p less than 0.05); this effect did not reach statistical significance for the lateral ventricles. Ventricle size in the patient sample increased with age, duration of illness, and number of depressive episodes. This effect was largely age-driven for the third ventricle. Enlargement of the anterior horns appeared to be primarily influenced by the combined effects of early onset and bipolarity of illness. Densitometric measurements of the grey and white matter did not show significant correlations with age, number, or frequency of depressive episodes, age of onset, or duration of illness.","Aged;Aged, 80 and over;Caudate Nucleus/*pathology;Cerebral Ventricles/*pathology;Dementia/diagnosis/*pathology/psychology;Depressive Disorder/diagnosis/*pathology/psychology;Female;Frontal Lobe/pathology;Humans;Hypertrophy/pathology;Male;Mental Status Schedule;Middle Aged;Parietal Lobe/pathology;Personality Tests;Prospective Studies;Thalamus/pathology;Tomography, X-Ray Computed","Beats, B.;Levy, R.;Forstl, H.",1991,Sep 1,,0,
5439,Decreased bilateral frontal lobe perfusion in dementia of amyotrophic lateral sclerosis,"A 59-year-old woman with amyotrophic lateral sclerosis (ALS) and normal results of brain MRI was evaluated for slowly progressive dementia. A Tc-99m biscate (technetium 99m-biscate ethyl cysteinate dimer) study showed diffuse, regional decreased blood flow in the bilateral frontal lobes. This pattern conforms the previously described pattern of bilateral decreased frontal lobe perfusion as quantified by O-15 water positron emission tomography and other blood flow tracers such as I-123 iodoamphetamine. This dementia associated with ALS is thought to be related to this pattern of decreased blood flow. MRI may show degeneration of the pyramidal tracts in patients with ALS, but this is inconsistent finding. Tc-99m ECD brain SPECT may be useful to identify patients with dementia of ALS, thus differentiating this entity from other causes of dementia, such as Alzheimer's disease or multiple-infarct dementia from cerebral vascular disease. Identifying this pattern and establishing this diagnosis may obviate the need for further evaluation of potentially correctable causes of dementia.",cysteine ethyl ester tc 99m;iofetamine i 123;adult;Alzheimer disease;amyotrophic lateral sclerosis;article;brain blood flow;case report;cerebrovascular disease;dementia;female;frontal lobe;human;multiinfarct dementia;nuclear magnetic resonance imaging;positron emission tomography;single photon emission computer tomography,"Beall, D. P.;Martin, D.;Chin, B. B.",1998,,,0,
5440,A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms,"Objective: To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is strongly associated with processing speed, the predominantly affected cognitive domain in SVD. Methods: We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity [PSMD]) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study. Results: PSMD was associated with processing speed in all study samples with SVD (p-values between 2.8 × 10−3 and 1.8 × 10−10). PSMD explained most of the variance in processing speed (R2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers. Interpretation: PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581–592.",adult;aged;Alzheimer disease;article;brain hemorrhage;brain size;brain ventricle;CADASIL;cerebrovascular disease;controlled study;diagnostic test accuracy study;diagnostic value;diffusion tensor imaging;disease association;disease course;female;histogram;human;image processing;imaging software;longitudinal study;major clinical study;male;mild cognitive impairment;neuroimaging;nuclear magnetic resonance scanner;priority journal;reproducibility;white matter;1.5T Siemens Magnetom Aera scanner;1.5T Siemens Magnetom Sonata scanner;1.5T Signa scanner;3T Magnetom Verio scanner;3T Siemens Magnetom Tim Trio scanner;Discovery MR750;Intera 3T scanner;Signa HDxt,"Baykara, E.;Gesierich, B.;Adam, R.;Tuladhar, A. M.;Biesbroek, J. M.;Koek, H. L.;Ropele, S.;Jouvent, E.;Chabriat, H.;Ertl-Wagner, B.;Ewers, M.;Schmidt, R.;de Leeuw, F. E.;Biessels, G. J.;Dichgans, M.;Duering, M.",2016,,10.1002/ana.24758,0,5441
5441,A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms,"OBJECTIVE: To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is strongly associated with processing speed, the predominantly affected cognitive domain in SVD. METHODS: We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity [PSMD]) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study. RESULTS: PSMD was associated with processing speed in all study samples with SVD (p-values between 2.8 x 10-3 and 1.8 x 10-10 ). PSMD explained most of the variance in processing speed (R2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers. INTERPRETATION: PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016.",,"Baykara, E.;Gesierich, B.;Adam, R.;Tuladhar, A. M.;Biesbroek, J. M.;Koek, H. L.;Ropele, S.;Jouvent, E.;Chabriat, H.;Ertl-Wagner, B.;Ewers, M.;Schmidt, R.;de Leeuw, F. E.;Biessels, G. J.;Dichgans, M.;Duering, M.",2016,Aug 12,10.1002/ana.24758,0,
5442,The carotid plaque imaging in acute stroke (CAPIAS) study: Protocol and initial baseline data,"Background: In up to 30% of patients with ischemic stroke no definite etiology can be established. A significant proportion of cryptogenic stroke cases may be due to non-stenosing atherosclerotic plaques or low grade carotid artery stenosis not fulfilling common criteria for atherothrombotic stroke. The aim of the CAPIAS study is to determine the frequency, characteristics, clinical and radiological long-term consequences of ipsilateral complicated American Heart Association lesion type VI (AHA-LT VI) carotid artery plaques in patients with cryptogenic stroke. Methods/Design: 300 patients (age >49 years) with unilateral DWI-positive lesions in the anterior circulation and non- or moderately stenosing (<70% NASCET) internal carotid artery plaques will be enrolled in the prospective multicenter study CAPIAS. Carotid plaque characteristics will be determined by high-resolution black-blood carotid MRI at baseline and 12 month follow up. Primary outcome is the prevalence of complicated AHA-LT VI plaques in cryptogenic stroke patients ipsilateral to the ischemic stroke compared to the contralateral side and to patients with defined stroke etiology. Secondary outcomes include the association of AHA-LT VI plaques with the recurrence rates of ischemic events up to 36 months, rates of new ischemic lesions on cerebral MRI (including clinically silent lesions) after 12 months and the influence of specific AHA-LT VI plaque features on the progression of atherosclerotic disease burden, on specific infarct patterns, biomarkers and aortic arch plaques. Discussion: CAPIAS will provide important insights into the role of non-stenosing carotid artery plaques in cryptogenic stroke. The results might have implications for our understanding of stroke mechanism, offer new diagnostic options and provide the basis for the planning of targeted interventional studies. Trial Registration: NCT01284933. © 2013 Bayer-Karpinska et al.; licensee BioMed Central Ltd.",,"Bayer-Karpinska, A.;Schwarz, F.;Wollenweber, F. A.;Poppert, H.;Boeckh-Behrens, T.;Becker, A.;Clevert, D. A.;Nikolaou, K.;Opherk, C.;Dichgans, M.;Saam, T.",2013,,,0,
5443,Reversible cerebral vasoconstriction syndrome with concurrent bilateral carotid artery dissection,"Background: The pathophysiological basis of reversible cerebral vasoconstriction syndrome is poorly understood but carotid artery dissection has been discussed as a rare possible cause. So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported. Case: Here, we describe the case of a 54-year old patient presenting to the emergency department with right hemiparesis, hypaesthesia and dysarthria. Furthermore, he reported two episodes of thunderclap headache after autosexual activity. Cerebral imaging showed ischaemic infarcts, slight cortical subarachnoid haemorrhage, bilateral carotid artery dissection and fluctuating intracranial vessel irregularities, compatible with reversible cerebral vasoconstriction syndrome. An extensive diagnostic work-up was normal. No typical trigger factors of reversible cerebral vasoconstriction syndrome could be found. The patient received intravenous heparin and the calcium channel blocker nimodipine. Followup imaging revealed no vessel irregularities, the left internal carotid artery was still occluded. Conclusion: This case supports the assumption that carotid artery dissection should be considered as a potential trigger of reversible cerebral vasoconstriction syndrome, possibly by altering sympathetic vascular tone. © 2013 International Headache Society.",,"Bayer-Karpinska, A.;Patzig, M.;Adamczyk, C.;Dimitriadis, K.;Wollenweber, F. A.;Dichgans, M.;Jahn, K.;Opherk, C.",2013,May,,0,
5444,Relationship of cognitive measures and gray and white matter in Alzheimer's disease,"OBJECTIVE: To examine the relationship between commonly used screening cognitive measures with gray and white matter integrity in patients with mild to moderate AD. BACKGROUND: New neuroimaging techniques, such as voxel-based morphometry (VBM), make it possible to study the relationship between structural brain integrity and cognitive functioning in AD. METHODS: Gray and white matter integrity was evaluated using VBM in fifteen patients with mild to moderate AD. ADAS-Cog and MMSE scores were also performed as part of the baseline assessment for a larger clinical trial in the AD patients. Correlations between cognitive measures and VBM were performed. RESULTS: Both the ADAS-Cog and the MMSE showed a similar relationship with gray matter degeneration, reflecting greater cognitive impairment with decreased gray matter in the left temporal lobe. However, the MMSE score was much more reflective of underlying white matter changes than ADAS-Cog scores, particularly in frontotemporal region. These findings suggest that the ADAS-Cog and MMSE reflect different aspects of the underlying brain changes observed in AD. The ADAS-Cog was more specific to gray matter integrity whereas the MMSE reflected a more global reduction in both gray and white matter. CONCLUSIONS: These results support using neuroimaging markers of neural integrity as an important consideration when evaluating treatment efficacy. Furthermore, whole-brain analyses such as VBM help to evaluate neural systems that are not necessarily targeted by the treatment.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology/physiopathology/ psychology;Brain/ pathology/physiopathology;Cerebral Ventricles/pathology/physiopathology;Cognition/ physiology;Double-Blind Method;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychomotor Performance/drug effects;Temporal Lobe/pathology/physiopathology","Baxter, L. C.;Sparks, D. L.;Johnson, S. C.;Lenoski, B.;Lopez, J. E.;Connor, D. J.;Sabbagh, M. N.",2006,Aug,,0,5445
5445,Relationship of cognitive measures and gray and white matter in Alzheimer's disease,"OBJECTIVE: To examine the relationship between commonly used screening cognitive measures with gray and white matter integrity in patients with mild to moderate AD. BACKGROUND: New neuroimaging techniques, such as voxel-based morphometry (VBM), make it possible to study the relationship between structural brain integrity and cognitive functioning in AD. METHODS: Gray and white matter integrity was evaluated using VBM in fifteen patients with mild to moderate AD. ADAS-Cog and MMSE scores were also performed as part of the baseline assessment for a larger clinical trial in the AD patients. Correlations between cognitive measures and VBM were performed. RESULTS: Both the ADAS-Cog and the MMSE showed a similar relationship with gray matter degeneration, reflecting greater cognitive impairment with decreased gray matter in the left temporal lobe. However, the MMSE score was much more reflective of underlying white matter changes than ADAS-Cog scores, particularly in frontotemporal region. These findings suggest that the ADAS-Cog and MMSE reflect different aspects of the underlying brain changes observed in AD. The ADAS-Cog was more specific to gray matter integrity whereas the MMSE reflected a more global reduction in both gray and white matter. CONCLUSIONS: These results support using neuroimaging markers of neural integrity as an important consideration when evaluating treatment efficacy. Furthermore, whole-brain analyses such as VBM help to evaluate neural systems that are not necessarily targeted by the treatment.","Alzheimer Disease [pathology] [physiopathology] [psychology];Brain [pathology] [physiopathology];Cerebral Ventricles [pathology] [physiopathology];Cognition [physiology];Double-Blind Method;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Neuropsychological Tests;Psychomotor Performance [drug effects];Temporal Lobe [pathology] [physiopathology];Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Baxter, L. C.;Sparks, D. L.;Johnson, S. C.;Lenoski, B.;Lopez, J. E.;Connor, D. J.;Sabbagh, M. N.",2006,,,0,
5446,"It is unclear if adjusting cortical thickness for changes in gray/white matter intensity ratio improves discrimination between normal aging, MCI, and AD","The contrast between gray and white matter in MRI is critical for accurately measuring cortical thickness. The gray/white matter intensity ratio (GWIR) has been proposed to be an important adjustment factor for cortical thickness measures in Alzheimer's disease (AD) and mild cognitive impairment (MCI). This study examined the GWIR and its influence on cortical thickness in normal aging, mild cognitive impairment (MCI), and AD. The ability for GWIR to discriminate between these groups was assessed on its own and as an adjustment factor for cortical thickness. Minimal age- and AD-related changes in GWIR were observed. GWIR was not able to differentiate between normal aging, MCI, and AD. However, adjusting cortical thickness for GWIR slightly improved the ability to discriminate between groups and the effect size of cortical thickness increased after adjusting for GWIR. This work demonstrates the ambiguity in adjusting cortical thickness measures for GWIR, particularly when attempting to discriminate between normal aging, MCI, and AD groups.","Aged;Aging/*pathology;Alzheimer Disease/*diagnosis/*pathology;Cerebral Cortex/*pathology;Diagnosis, Differential;Female;Humans;Image Interpretation, Computer-Assisted/methods;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/*diagnosis/*pathology;Nerve Fibers, Unmyelinated/pathology;Neuropsychological Tests;Organ Size;ROC Curve;Sensitivity and Specificity","Bauer, C. M.;Cabral, H. J.;Killiany, R. J.",2014,Mar,10.1007/s11682-013-9268-6,0,
5447,Child overweight and obesity are associated with reduced executive cognitive performance and brain alterations: a magnetic resonance imaging study in Mexican children,"BACKGROUND: Overweight and obesity in childhood is associated with negative physical and psychological effects. It has been proposed that obesity increase the risk for developing cognitive deficits, dementia and Alzheimer's disease and that it may be associated with marked differences in specific brain structure volumes. OBJECTIVE: The purpose of this study was a neurobiopsychological approach to examine the association between overweight and obesity, brain structure and a paediatric neuropsychological assessment in Mexican children between 6 and 8 years of age. METHODS: We investigated the relation between the body mass index (BMI), brain volumetric segmentation of subcortical gray and white matter regions obtained with magnetic resonance imaging and the Neuropsychological Assessment of Children standardized for Latin America. Thirty-three healthy Mexican children between 6 and 8 years of age, divided into normal weight (18 children) and overweight/obese (15 children) groups. RESULTS: Overweight/obese children showed reduced executive cognitive performance on neuropsychological evaluations (i.e. verbal fluidity, P = 0.03) and presented differences in brain structures related to learning and memory (reduced left hippocampal volumes, P = 0.04) and executive functions (larger white matter volumes in the left cerebellum, P = 0.04 and mid-posterior corpus callosum, P = 0.03). Additionally, we found a positive correlation between BMI and left globulus pallidus (P = 0.012, rho = 0.43) volume and a negative correlation between BMI and neuropsychological evaluation scores (P = 0.033, rho = -0.37). CONCLUSIONS: The findings contribute to the idea that there is a relationship between BMI, executive cognitive performance and brain structure that may underlie the causal chain that leads to obesity in adulthood.",,"Bauer, C. C.;Moreno, B.;Gonzalez-Santos, L.;Concha, L.;Barquera, S.;Barrios, F. A.",2015,Jun,10.1111/ijpo.241,0,
5448,Regional cerebral blood flow study with 99mTc-hexamethyl-propyleneamine oxime single photon emission computed tomography in Alzheimer's and multi-infarct dementia,"Thirty-four demented patients, 19 with Alzheimer's and 15 with multi-infarct dementia, were studied using single photon emission computed tomography, and 99mTc-hexamethyl-propylenemine oxime as a tracer of regional cerebral perfusion. Tracer activity ratios, determined in cortical and subcortical regions, were compared with those of 11 age-matched controls. In both groups of demented patients, most of the cortical regions showed significant declines in tracer uptake from control values, with the greatest reductions in the parietal cortex. Significantly lower parietal indexes were found in the Alzheimer's patient group as compared both to the control values and to the group of multi-infarct dementia patients. A positive correlation was found between the magnitude of the parietal deficits and the severity of dementia.","Aged;Alzheimer Disease/*radionuclide imaging;Basal Ganglia/blood supply;Brain/*blood supply;Cerebral Cortex/blood supply;Dementia, Multi-Infarct/*radionuclide imaging;Dominance, Cerebral/physiology;Female;Humans;Male;Middle Aged;Neuropsychological Tests;*Organotechnetium Compounds;*Oximes;Regional Blood Flow/physiology;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/*methods","Battistin, L.;Pizzolato, G.;Dam, M.;Ponza, I.;Borsato, N.;Zanco, P. L.;Ferlin, G.",1990,,,0,
5449,Hereditary diffuse leukoencephalopathy with axonal spheroids: Three patients with stroke-like presentation carrying new mutations in the CSF1R gene,"Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant disorder characterized by white matter neurodegeneration, progressive cognitive decline, and motor symptoms. Histologically, it is characterized by axonal swellings (""spheroids""). To date, over 20 different mutations affecting the tyrosine kinase domain of the protein have been identified in the colony stimulating factor 1 receptor (CSF1R) gene. Our goal is to describe three unrelated Italian patients affected by HDLS and carrying new CSF1R mutations, thus expanding the mutational spectrum and phenotypic presentation. CSF1R gene analysis was performed in 15 patients (age range 25-83 years) with undefined leukoencephalopathy and progressive cognitive decline. In three patients (two males and one female, aged 58, 37, and 48 years, respectively), new heterozygous missense mutations affecting the protein tyrosine kinase domain of the CSF1R gene were detected. In all of these patients, behavioural and cognitive changes were preceded by an ischemic stroke-like episode. A positive family history was present in only one case. © 2014 Springer-Verlag Berlin Heidelberg.",protein tyrosine kinase;adult;apathy;aphasia;article;behavior change;brain ischemia;case report;cognitive defect;CSF1R gene;diffusion weighted imaging;family history;female;gene;gene mutation;genetic analysis;headache;hemiparesis;hereditary diffuse leukoencephalopathy with axonal spheroid;heterozygote;human;leukoencephalopathy;male;mental disease;middle aged;missense mutation;mutational analysis;nerve degeneration;neuroimaging;neurologic examination;nuclear magnetic resonance imaging;priority journal;tonic clonic seizure;transient ischemic attack,"Battisti, C.;Di Donato, I.;Bianchi, S.;Monti, L.;Formichi, P.;Rufa, A.;Taglia, I.;Cerase, A.;Dotti, M. T.;Federico, A.",2014,,,0,
5450,Can MR measurement of intracranial hydrodynamics and compliance differentiate which patient with idiopathic normal pressure hydrocephalus will improve following shunt insertion?,"BACKGROUND: Between 10 and 90% of patients with normal pressure hydrocephalus (NPH) treated with a shunt will improve but they risk significant morbidity/mortality from this procedure. NPH is treated hydrodynamically and it has been assumed that a hydrodynamic difference must exist to differentiate which patient will respond. The purpose of this study is to see whether MRI hydrodynamics can differentiate which patients will improve post shunting. METHOD: Thirty-two patients with NPH underwent MRI with flow quantification measuring the degree of ventricular enlargement, sulcal compression, white matter disease, total blood inflow, sagittal sinus outflow, aqueduct stroke volume, relative compliance ratio and arteriovenous delay. Patients were followed up after shunt insertion to gauge the degree of improvement and were compared with 12 age-matched controls and 12 patients with Alzheimer's disease. FINDINGS: 63% of patients improved with insertion. The responders were identical to the non-responders in all variables. The NPH patients were significantly different to the controls (e.g. Total blood inflow reduced 20%, sagittal sinus outflow reduced 35%, aqueduct stroke volume increased 210%, relative compliance ratio reduced 60% and arteriovenous delay reduced 57% with p = 0.007, 0.03, 0.04, 0.0002 and 0.0003 respectively. The patient's with Alzheimer's disease values were midway between the NPH and control patients. CONCLUSIONS: Significant hydrodynamic differences were noted between NPH and controls but these were unable to differentiate the responders from non-responders. The hydrodynamics of Alzheimer's disease makes exclusion of comorbidity from this disease difficult.","Aged;Aged, 80 and over;Blood Flow Velocity/physiology;Cerebral Ventricles/pathology/physiopathology;*Cerebrospinal Fluid Shunts;Cerebrovascular Circulation/*physiology;Compliance;Female;Follow-Up Studies;Humans;Hydrocephalus, Normal Pressure/pathology/*physiopathology/*surgery;*Magnetic Resonance Imaging;Male;Predictive Value of Tests;Retrospective Studies;Treatment Outcome","Bateman, G. A.;Loiselle, A. M.",2007,,10.1007/s00701-007-1142-0,0,
5451,Cobalamin in blood and cerebrospinal fluid in Alzheimer's disease and related disorders,"Cerebrospinal fluid (CSF) and serum levels of cobalamin were studied in 35 subjects with dementia and in 7 healthy volunteers with no clinical or family history of dementia. The demented patiens were classified into three groups according to DSM-III-R: dementia of Alzheimer-type (DAT), multi-infarct dementia (MID) and dementia not otherwise specified (DNOS). The CSF concentrations of cobalamin were significantly reduced in the DAT and MID cases. There were correlations between CSF and serumk levels of cobalamin in the patient groups. The cobalamin levels in CSF were not related to cognitive functioning, behavior or degree of dementia, respectively. The subarachnoid spaces, ventricles and white-matter changes in the brain were observed on magnetic resonance imaging. The volumes were calculated in the DAT group, but there were no correlations to CSF or serum concentrations of cobalamin. The significance of low CSF cobalamin is discussed in relation to the metabolism of the brain.",,"Basun, H.;Forsell, L. G.;Bendz, R.;Wahlund, L. O.;Wetterberg, L.;Winblad, B.",1991,1991,,0,
5452,The contribution of medial temporal lobe atrophy and vascular pathology to cognitive impairment in vascular dementia,"BACKGROUND AND PURPOSE: Besides cerebrovascular disease, medial temporal lobe atrophy (MTA), a neuroimaging finding suggestive of degenerative pathology, has been shown in vascular dementia (VaD). However, it is unknown to what extent MTA contributes to the pattern of cognitive impairment observed in VaD. Therefore, our purpose was to investigate the relative contribution of cerebrovascular disease and MTA to cognitive impairment in patients fulfilling diagnostic criteria for VaD. METHODS: We examined 590 patients (374 men; mean age, 73 years; standard deviation, 8) with probable VaD according to the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria at inclusion into a multicenter clinical trial. Cerebrovascular disease and the degree of MTA were evaluated by using MRI. Cognitive testing included the Mini-Mental State Examination, and the vascular dementia assessment scale. RESULTS: On the basis of the operational definitions for the neuroimaging part of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, 485 (82.2%) patients had small vessel VaD and 153 (25.9%) had large vessel VaD. More than half (59.8%) of the patients had considerable MTA. Multiple linear regression analyses revealed that after correction for sex, age, education, and duration of dementia, neuropsychological tests showed that patients with higher grades of MTA or large vessel VaD had significantly worse general cognitive and executive functioning, whereas associations with small vessel disease were restricted to worse executive functioning. CONCLUSIONS: Both MTA and large vessel disease contribute to global cognitive impairment in VaD. Small vessel disease contributes to executive dysfunction.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology;*Atrophy;Cerebrovascular Disorders/*diagnosis/*pathology;Cognition;Cognition Disorders/*diagnosis/*pathology;Dementia, Vascular/*diagnosis/*pathology;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging/*methods;Male;Middle Aged;Stroke/*diagnosis/*pathology;Temporal Lobe/*pathology","Bastos-Leite, A. J.;van der Flier, W. M.;van Straaten, E. C.;Staekenborg, S. S.;Scheltens, P.;Barkhof, F.",2007,Dec,10.1161/strokeaha.107.490102,0,
5453,Thalamic lesions in vascular dementia: low sensitivity of fluid-attenuated inversion recovery (FLAIR) imaging,"BACKGROUND AND PURPOSE: The criteria of the National Institute of Neurological Disorders and Stroke (NINDS)-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) include thalamic lesions for the diagnosis of vascular dementia (VaD). Although studies concerning VaD and brain aging advocate the use of fluid-attenuated inversion recovery (FLAIR) or T2-weighted images (T2-WI) to detect ischemic lesions, none compared the sensitivity of these sequences to depict thalamic lesions. METHODS: We performed a blinded review of T2-WI and FLAIR images in 73 patients fulfilling the radiological part of the NINDS-AIREN criteria (mean age, 71 years; range, 49 to 83 years). This sample was drawn from a large multicenter trial on VaD and was expected to have a high prevalence of thalamic lesions. In a side-by-side review, including T1-weighted images as well, lesions were classified according to presumed underlying pathology. RESULTS: The total number of thalamic lesions was 214. Two hundred eight (97%) were detected on T2-WI, but only 117 (55%) were detected on FLAIR (chi(2)=5.1; P<0.05). Although the mean size of lesions detected on T2-WI and not on FLAIR (4.4 mm) was significantly lower than the mean size of lesions detected on both sequences (6.7 mm) (P<0.001), 5 of the 29 lesions >10 mm on T2-WI were not visible on FLAIR. FLAIR detected only 81 (51%) of the 158 probable ischemic lesions and 30 (60%) of the 50 probable microbleeds. CONCLUSIONS: FLAIR should not be used as the only T2-weighted sequence to detect thalamic lesions in patients suspected of having VaD.","Aged;Aged, 80 and over;Carbamates/therapeutic use;Clinical Trials, Phase III as Topic/statistics & numerical data;Dementia, Vascular/ diagnosis/drug therapy/ pathology;Humans;Magnetic Resonance Imaging/methods/ statistics & numerical data;Middle Aged;Multicenter Studies as Topic/statistics & numerical data;Phenylcarbamates;Predictive Value of Tests;Prospective Studies;Randomized Controlled Trials as Topic/statistics & numerical data;Rivastigmine;Sensitivity and Specificity;Single-Blind Method;Thalamus/ pathology","Bastos Leite, A. J.;van Straaten, E. C.;Scheltens, P.;Lycklama, G.;Barkhof, F.",2004,Feb,10.1161/01.str.0000109226.67085.5a,0,
5454,Tract shape modelling provides evidence of topological change in corpus callosum genu during normal ageing,"Understanding how ageing affects brain structure is an important challenge for medical science. By allowing segmentation of fasciculi-of-interest from diffusion magnetic resonance imaging (dMRI) data, tractography provides a promising tool for assessing white matter connectivity in old age. However, the output from tractography algorithms is usually strongly dependent on the subjective location of user-specified seed points, with the result that it can be both difficult and time consuming to identify the same tract reliably in cross-sectional studies. Here we investigate whether a novel method for automatic single seed point placement based on tract shape modelling, termed probabilistic model-based neighbourhood tractography (PNT), can reliably segment the same tract from subject to subject in a non-demented cohort aged over 65 years. For the fasciculi investigated (genu and splenium of corpus callosum, cingulum cingulate gyri, corticospinal tracts and uncinate fasciculi), PNT was able to provide anatomically plausible representations of the tract in question in 70 to 90% of subjects compared with 2.5 to 60% if single seed points were simply transferred directly from standard to native space. In corpus callosum genu there was a significant negative correlation between a PNT-derived measure of tract shape similarity to a young brain reference tract and age, and a trend towards a significant negative correlation between tract-averaged fractional anisotropy and age; results that are consistent with previous dMRI studies of normal ageing. These data show that it is possible automatically to segment comparable tracts in the brains of older subjects using single seed point tractography, if the seed point is carefully chosen.","Aging/ pathology;Algorithms;Computer Simulation;Corpus Callosum/ pathology;Diffusion Magnetic Resonance Imaging/ methods;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Models, Neurological;Nerve Fibers, Myelinated/ ultrastructure;Reproducibility of Results;Sensitivity and Specificity","Bastin, M. E.;Piatkowski, J. P.;Storkey, A. J.;Brown, L. J.;Maclullich, A. M.;Clayden, J. D.",2008,Oct 15,10.1016/j.neuroimage.2008.06.047,0,
5455,Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling,"Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40% and 84%, respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the ""frontal ageing"" hypothesis, there was a significant positive correlation between mean diffusivity (D) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between D and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity.","Aged;Aged, 80 and over;Aging/*pathology;Anisotropy;Artificial Intelligence;Automation;Body Water;Brain/*pathology;Cerebral Ventricles/pathology;Diffusion;Diffusion Magnetic Resonance Imaging/*methods;Female;Humans;Image Processing, Computer-Assisted/*methods;Male;Nerve Fibers, Myelinated/pathology;Neural Pathways/pathology;Organ Size;Probability","Bastin, M. E.;Munoz Maniega, S.;Ferguson, K. J.;Brown, L. J.;Wardlaw, J. M.;MacLullich, A. M.;Clayden, J. D.",2010,May 15,10.1016/j.neuroimage.2010.02.036,0,
5456,Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age,"Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T2-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically normal-appearing white matter (NAWM) and PVWMH in a cohort of normal older subjects. Forty-two non-demented 83-year olds underwent structural, diffusion tensor and magnetization transfer MRI. Mean diffusivity (<D>), fractional anisotropy (FA), axial (λax) and radial (λrad) diffusivity, and magnetization transfer ratio (MTR) were measured in both NAWM and PVWMH in frontal and parieto-occipital white matter, and centrum semiovale. For all three regions, PVWMH had greater <D>, λax and λrad than NAWM, while FA and MTR were significantly reduced compared with normal tissue (p ≪ 0.01). For PVWMH, MTR was significantly correlated (Spearman's ρ in the range -0.93 to 0.70; p < 0.01) with <D>, FA, λax and λrad in all three regions. Conversely, for NAWM, the only significant correlation between MTR and a water diffusion parameter was for λrad in parieto-occipital white matter (ρ = -0.40; p < 0.05), with all other correlations close to the ρ = 0 level. These data indicate that in normal white matter, characterized by structurally coherent cell membranes, the degree of water molecule diffusion and myelination are held within relatively tight limits. However, within PVWMH, MTR correlates strongly with water diffusion parameters probably because of the pathologically associated neuronal loss, demyelination and gliosis. © 2007 Elsevier Inc. All rights reserved.",aged;anisotropy;article;cognition;controlled study;diffusion tensor imaging;diffusion weighted imaging;female;frontal cortex;human;human experiment;image analysis;male;normal human;nuclear magnetic resonance imaging;occipital cortex;parietal lobe;priority journal;risk factor;senescence;vascular disease;white matter,"Bastin, M. E.;Clayden, J. D.;Pattie, A.;Gerrish, I. F.;Wardlaw, J. M.;Deary, I. J.",2009,,,0,
5457,Incident Cerebral Microbleeds Detected by Susceptibility Weight-Imaging Help to Identify Patients with Mild Cognitive Impairment Progressing to Alzheimer's Disease,"BACKGROUND: The relationship between cerebral microbleeds (CMB) and Alzheimer's disease (AD) has not yet been clearly determined, particularly with susceptibility weight-imaging (SWI). OBJECTIVE: To evaluate the SWI sequence using 3T MRI for the detection of CMB, and its ability to differentiate elderly control subjects (CS), stable mild cognitive impairment patients (MCI-s), MCI patients progressing to AD (MCI-p), and AD patients. METHODS: It was a prospective, monocentric, observational study that took place in Toulouse, France. Participants were 65 years and older, enrolled in three groups: CS, MCI, and AD. Based on the longitudinal analysis of cognitive decline, MCI subjects were retrospectively classified as MCI-s or MCI-p. Each patient had a 4-year follow-up with MRI at baseline (MRI#1) and during the fourth year (MRI#3). CMB were counted on native SWI images juxtaposed to minIP reformatted images. RESULTS: 150 patients were enrolled: 48 CS, 25 MCI-s, 18 MCI-p, 59 AD. At MRI#1 and at MRI#3, there was no significant difference in the prevalence of CMB between groups (p = 0.75 and p = 0.87). In the MCI-p + AD group, significantly more subjects had>/=4 incident CMB compared to the CS + MCI-s group (p = 0.016). In the MCI-p + AD group, the prevalence of patients with >4 CMB was significantly higher at MRI#3 than at MRI#1 (p = 0.008). CONCLUSION: Using SWI, AD and MCI-p patients had developed significantly more new CMB than CS and MCI-s patients during the follow-up. Incident CMB might be suggested as a potential imaging marker of AD progression.",Alzheimer's disease;disease progression;imaging biomarker;incident cerebral microbleeds;longitudinal MRI;mild cognitive impairment;susceptibility weight imaging,"Basselerie, H.;Bracoud, L.;Zeestraten, E.;Bouguen, E.;Kiyasova, V.;Pueyo, M.;Cognard, C.;Dumas, H.;Gramada, R.;Ousset, P. J.;Vellas, B.;Bonneville, F.",2017,,,0,
5458,Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases,"Tissue iron can promote oxidative damage. Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Higher iron levels in males may contribute to higher risk for younger-onset PD and recent studies have linked the presence of the hemochromatosis gene with a younger age at onset of AD. We examined whether age at onset of PD and AD was associated with increased brain ferritin iron. Ferritin iron can be measured with specificity in vivo with MRI utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in three basal ganglia regions (caudate, putamen, and globus pallidus) and frontal lobe white matter for younger- and older-onset male PD and AD patients and healthy controls. Significant increases in basal ganglia FDRI levels were observed in the younger-onset groups of both diseases compared to their respective control groups, but were absent in the older-onset patients. The results support the suggestion that elevated ferritin iron and its associated toxicity is a risk factor for age at onset of neurodegenerative diseases such as AD and PD. Clinical phenomena such as gender-associated risk of developing neurodegenerative diseases and the age at onset of such diseases may be associated with brain iron levels. In vivo MRI can measure and track brain ferritin iron levels and provides an opportunity to design therapeutic interventions that target high-risk populations early in the course of illness, possibly even before symptoms appear.","Age Factors;Age of Onset;Aged;Aged, 80 and over;Alzheimer Disease/metabolism/pathology;Brain/*metabolism/pathology;Case-Control Studies;Ferritins/*metabolism;Humans;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Middle Aged;Neurodegenerative Diseases/*epidemiology/*metabolism/pathology;Parkinson Disease/metabolism/pathology;*Risk Factors","Bartzokis, G.;Tishler, T. A.;Shin, I. S.;Lu, P. H.;Cummings, J. L.",2004,Mar,,0,
5459,Brain ferritin iron may influence age- and gender-related risks of neurodegeneration,"BACKGROUND: Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both genders. We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases. METHODS: The amount of iron in ferritin molecules (ferritin iron) was measured in vivo with MRI by utilizing the field dependent relaxation rate increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei [caudate (C), putamen (P), globus pallidus (G), thalamus (T)], three white matter regions [frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm)] and hippocampus (Hipp) in 165 healthy adults aged 19-82. RESULTS: There was a high correlation (r>0.99) between published post-mortem brain iron levels and FDRI. There were significant age-related changes in ferritin iron (increases in Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron than men in five regions (C, T, Fwm, Gwm, Swm). CONCLUSIONS: This is the first demonstration of gender differences in brain ferritin iron levels. It is possible that brain iron accumulation is a risk factor that can be modified. MRI provides the opportunity to assess brain iron levels in vivo and may be useful in targeting individuals or groups for preventive therapeutic interventions.","Adult;Aged;Aged, 80 and over;*Aging;Brain/*metabolism;Female;Ferritins/*chemistry/metabolism;Humans;Image Processing, Computer-Assisted/methods;Iron/*metabolism;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Degeneration/*pathology;Postmortem Changes;*Sex Characteristics","Bartzokis, G.;Tishler, T. A.;Lu, P. H.;Villablanca, P.;Altshuler, L. L.;Carter, M.;Huang, D.;Edwards, N.;Mintz, J.",2007,Mar,10.1016/j.neurobiolaging.2006.02.005,0,
5460,MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease,"BACKGROUND: The basal ganglia contain the highest levels of iron in the brain and post-mortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's disease (HD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD and HD brain. Magnetic resonance imaging (MRI) can quantify transverse relaxation rates, which can be used to quantify tissue iron stores as well as evaluate increases in MR-visible water (an indicator of tissue damage). METHODS: A magnetic resonance imaging (MRI) method termed the field dependent relaxation rate increase (FDRI) was employed which quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength MRI instruments. Three basal ganglia structures (caudate, putamen and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. Thirty-one patients with AD and a group of 68 older control subjects, and 11 patients with HD and a group of 27 adult controls participated (4 subjects overlap between AD and HD controls). RESULTS: Compared to their respective normal control groups, increases in basal ganglia FDRI levels were seen in both AD and HD. FDRI levels were significantly increased in the caudate (p = 0.007) and putamen (p = 0.008) of patients with AD with a trend toward an increase in the globus pallidus (p = 0.13). In the patients with HD, all three basal ganglia regions showed highly significant FDRI increases (p<0.001) and the magnitude of the increases were 2 to 3 times larger than those observed in AD versus control group comparison. For both HD andAD subjects, the basal ganglia FDRI increase was not a generalized phenomenon, as frontal lobe white matter FDRI levels were decreased in HD (p = 0.015) and remained unchanged in AD. Significant low field relaxation rate decreases (suggestive of increased MR-visible water and indicative of tissue damage) were seen in the frontal lobe white matter of both HD and AD but only the HD basal ganglia showed such decreases. CONCLUSIONS: The data suggest that basal ganglia ferritin iron is increased in HD and AD. Furthermore, the increased iron levels do not appear to be a byproduct of the illness itself since they seem to be present at the onset of the diseases, and thus may be considered a putative risk factor. Published post-mortem studies suggest that the increase in basal ganglia ferritin iron may occur through different mechanisms in HD and AD. Consistent with the known severe basal ganglia damage, only HD basal ganglia demonstrated significant decreases in low field relaxation rates. MRI can be used to dissect differences in tissue characteristics, such as ferritin iron and MR-visible water, and thus could help clarify neuropathologic processes in vivo. Interventions aimed at decreasing brain iron levels, as well as reducing the oxidative stress associated with increased iron levels, may offer novel ways to delay the rate of progression and possibly defer the onset of AD and HD.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Basal Ganglia/ metabolism/pathology;Case-Control Studies;Female;Ferritins/ chemistry/ metabolism;Humans;Huntington Disease/ pathology;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged","Bartzokis, G.;Tishler, T. A.",2000,Jun,,0,
5461,In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI,"Magnetic resonance imaging (MRI) can measure transverse relaxation rate (R2) of tissues. Although R2 is increased by tissue iron levels, R2 is not a specific measure of iron. A new method, based on the fact that ferritin (the primary tissue iron storage protein) affects R2 in a field-dependent manner, can quantify tissue iron with specificity by measuring the Field Dependent R2 Increase (FDRI). Using the FDRI method, we compared brain iron stores in frontal white matter, caudate nucleus, putamen, and globus pallidus of five male patients with Alzheimer disease (AD) and eight age and gender-matched normal controls. FDRI values were significantly higher among AD patients in the caudate and globus pallidus. The data suggest that AD may involve disturbances in brain iron metabolism and that the involvement of iron in the pathophysiology of age-related neurodegenerative disorders can be investigated in vivo using MRI.",Aged;Alzheimer Disease/ diagnosis/metabolism;Basal Ganglia/chemistry/metabolism;Brain Chemistry;Caudate Nucleus/chemistry/metabolism;Cross-Sectional Studies;Frontal Lobe/chemistry/metabolism;Globus Pallidus/metabolism/ radiography;Humans;Iron/ analysis/metabolism;Magnetic Resonance Imaging;Male;Pilot Projects;Putamen/chemistry/metabolism,"Bartzokis, G.;Sultzer, D.;Mintz, J.;Holt, L. E.;Marx, P.;Phelan, C. K.;Marder, S. R.",1994,Apr 1,,0,
5462,"Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical ""disconnection"" in aging and Alzheimer's disease","Human and non-human primate data suggest that the structural integrity of myelin sheaths deteriorates during normal aging, especially in the late-myelinating association regions and may result in ""disconnection"" of widely distributed neural networks. Magnetic resonance imaging (MRI) was used to assess the heterogeneity of this process and its impact on brain aging and Alzheimer's disease (AD) by evaluating early- and later-myelinating regions of the corpus callosum, the splenium (Scc) and genu (Gcc), respectively. Calculated transverse relaxation rates (R2), an indirect measure of white matter structural integrity for the Gcc and Scc, were examined. The relationship between age and R2 differed in the two regions. A quadratic (inverted U) function with an accelerating rate of decline beginning at age 31 best represented the Gcc pattern while the Scc decline was three-fold smaller, gradual, and linear. These data suggest that the severity of age-related myelin breakdown is regionally heterogeneous, consistent with the hypothesis that differences in myelin properties make later-myelinating regions more susceptible to this process. In AD this process is globally exacerbated, consistent with an extracellular deleterious process such as amyloid beta-peptide toxicity. Non-invasive measures such as R2 may be useful in primary prevention studies of AD.","Adolescent;Adult;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ diagnosis;Corpus Callosum/anatomy & histology/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/ pathology/physiology;Nerve Net/physiology;Reference Values;Regression Analysis","Bartzokis, G.;Sultzer, D.;Lu, P. H.;Nuechterlein, K. H.;Mintz, J.;Cummings, J. L.",2004,Aug,10.1016/j.neurobiolaging.2003.09.005,0,
5463,In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging,"BACKGROUND: The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method. METHODS: Thirty-one patients with AD and 68 control subjects participated in this study. A magnetic resonance imaging method was employed that quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength magnetic resonance imaging instruments. Three basal ganglia structures (caudate, putamen, and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia ferritin iron levels were significantly increased in the caudate (P = .007; effect size, 0.69) and putamen (P = .008; effect size, 0.67) of AD subjects, with a trend toward an increase in the globus pallidus (P = .13). The increased basal ganglia ferritin iron levels were not a generalized phenomenon; white matter ferritin iron levels were unchanged in patients with AD (P = .50). CONCLUSIONS: The data replicate and extend prior results and suggest that basal ganglia ferritin iron levels are increased in AD. Prospective studies are needed to evaluate whether premorbid iron levels are increased in individuals who develop AD.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis/metabolism;Basal Ganglia/ chemistry/metabolism;Caudate Nucleus/chemistry/metabolism;Female;Ferritins/analysis/ metabolism;Globus Pallidus/chemistry/metabolism;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Putamen/chemistry/metabolism","Bartzokis, G.;Sultzer, D.;Cummings, J.;Holt, L. E.;Hance, D. B.;Henderson, V. W.;Mintz, J.",2000,Jan,,0,
5464,Reliability of in vivo volume measures of hippocampus and other brain structures using MRI,"Volume reductions of the hippocampus are associated with Alzheimer's disease, schizophrenia, and epilepsy. We used clinically available MRI methods (2D acquisition; inversion recovery and calculated T(2) images; 3 mm contiguous slices) that optimize image contrast, quality, and resolution and standardized positioning protocols to maximize the in vivo accuracy (test- retest reliability) of brain volume measurements in volunteers who were scanned two or three times. Volunteers were scanned in the same MRI instrument (intrascanner reliability) as well as in two different instruments (interscanner reliability). A single rater obtained brain volume measures of seven contiguous slices centered on the anterior commissure. The in vivo intrascanner reliability for measures of anterior hippocampus and ventricular volumes was very good, with reliability coefficients [intraclass r (r(xx))] ranging between .855 and .997, and a median coefficient of variation (CV) of 6.4%. Reliability was good for amygdala (r(xx) of .740 and .764) and for total frontal and temporal lobe volumes and white matter volume measures (r(xx) ranging between .640 and .823, median coefficient of variation was 3.2%). Overall, interscanner reliability was also good. We discuss the implications of our results relative to the possible clinical utility of hippocampal quantification and the feasibility of prospective studies aimed at quantifying progressive neurodegeneration.",,"Bartzokis, G.;Mintz, J.;Marx, P.;Osborn, D.;Gutkind, D.;Chiang, F.;Phelan, C. K.;Marder, S. R.",1993,1993,,0,
5465,Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men,"Prevalent gene variants involved in iron metabolism [hemochromatosis (HFE) H63D and transferrin C2 (TfC2)] have been associated with higher risk and earlier age at onset of Alzheimer's disease (AD), especially in men. Brain iron increases with age, is higher in men, and is abnormally elevated in several neurodegenerative diseases, including AD and Parkinson's disease, where it has been reported to contribute to younger age at onset in men. The effects of the common genetic variants (HFE H63D and/or TfC2) on brain iron were studied across eight brain regions (caudate, putamen, globus pallidus, thalamus, hippocampus, white matter of frontal lobe, genu, and splenium of corpus callosum) in 66 healthy adults (35 men, 31 women) aged 55 to 76. The iron content of ferritin molecules (ferritin iron) in the brain was measured with MRI utilizing the Field Dependent Relaxation Rate Increase (FDRI) method. 47% of the sample carried neither genetic variant (IRON-) and 53% carried one and/or the other (IRON+). IRON+ men had significantly higher FDRI compared to IRON- men (p=0.013). This genotype effect was not observed in women who, as expected, had lower FDRI than men. This is the first published evidence that these highly prevalent genetic variants in iron metabolism genes can influence brain iron levels in men. Clinical phenomena such as differential gender-associated risks of developing neurodegenerative diseases and age at onset may be associated with interactions between iron genes and brain iron accumulation. Clarifying mechanisms of brain iron accumulation may help identify novel interventions for age-related neurodegenerative diseases. © 2010 - IOS Press and the authors.",apolipoprotein E4;ferritin;HFE protein;iron;transferrin;transferrin c2;unclassified drug;adult;aged;article;caudate nucleus;controlled study;corpus callosum;female;ferritin blood level;frontal lobe;genetic variability;genotype;globus pallidus;hippocampus;human;human experiment;iron blood level;iron metabolism;male;normal human;nuclear magnetic resonance imaging;priority journal;putamen;thalamus;white matter,"Bartzokis, G.;Lu, P. H.;Tishler, T. A.;Peters, D. G.;Kosenko, A.;Barrall, K. A.;Finn, J. P.;Villablanca, P.;Laub, G.;Altshuler, L. L.;Geschwind, D. H.;Mintz, J.;Neely, E.;Connor, J. R.",2010,,,0,
5466,Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications,"BACKGROUND: Postmortem and in vivo imaging data support the hypothesis that premature myelin breakdown and subsequent homeostatic remyelination attempts with increased oligodendrocyte and iron levels may contribute to Huntington's Disease (HD) pathogenesis and the symmetrical progress of neuronal loss from earlier-myelinating striatum to later-myelinating regions. A unique combination of in vivo tissue integrity and iron level assessments was used to examine the hypothesis. METHODS: A method that uses two Magnetic resonance imaging (MRI) instruments operating at different field-strengths was used to quantify the iron content of ferritin molecules (ferritin iron) as well as tissue integrity in eight regions in 11 HD and a matched group of 27 healthy control subjects. Three white matter regions were selected based on their myelination pattern (early to later-myelinating) and fiber composition. These were frontal lobe white matter (Fwm) and splenium and genu of the corpus callosum (Swm and Gwm). In addition, gray matter structures were also chosen based on their myelination pattern and fiber composition. Three striatum structures were assessed [caudate, putamen, and globus pallidus (C, P, and G)] as well as two comparison gray matter regions that myelinate later in development and are relatively spared in HD [Hippocampus (Hipp) and Thalamus (Th)]. RESULTS: Compared to healthy controls, HD ferritin iron levels were significantly increased in striatum C, P, and G, decreased in Fwm and Gwm, and were unchanged in Hipp, Th, and Swm. Loss of tissue integrity was observed in C, P, Fwm, and especially Swm but not Hipp, Th, G, or Gwm. This pattern of findings was largely preserved when a small subset of HD subjects early in the disease process was examined. CONCLUSIONS: The data suggest early in the HD process, myelin breakdown and changes in ferritin iron distribution underlie the pattern of regional toxicity observed in HD. Prospective studies are needed to verify myelin breakdown and increased iron levels are causal factors in HD pathogenesis. Tracking the effects of novel interventions that reduce myelin breakdown and iron accumulation in preclinical stages of HD could hasten the development of preventive treatments.","Adult;Aged;Brain/pathology;Brain Chemistry/physiology;Data Interpretation, Statistical;Female;Ferritins/metabolism;Humans;Huntington Disease/ metabolism/ pathology/therapy;Image Processing, Computer-Assisted;Iron/ metabolism;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/ pathology","Bartzokis, G.;Lu, P. H.;Tishler, T. A.;Fong, S. M.;Oluwadara, B.;Finn, J. P.;Huang, D.;Bordelon, Y.;Mintz, J.;Perlman, S.",2007,Oct,10.1007/s11064-007-9352-7,0,
5467,Gender and iron genes may modify associations between brain iron and memory in healthy aging,"Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders that impact memory including Alzheimer's disease (AD). Higher brain iron levels are associated with male gender and presence of highly prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2)). In this study, we examined whether in healthy older individuals memory performance is associated with increased brain iron, and whether gender and gene variant carrier (IRON+) vs noncarrier (IRON-) status (for HFE H63D/TfC2) modify the associations. Tissue iron deposited in ferritin molecules can be measured in vivo with magnetic resonance imaging utilizing the field-dependent relaxation rate increase (FDRI) method. FDRI was assessed in hippocampus, basal ganglia, and white matter, and IRON+ vs IRON- status was determined in a cohort of 63 healthy older individuals. Three cognitive domains were assessed: verbal memory (delayed recall), working memory/attention, and processing speed. Independent of gene status, worse verbal-memory performance was associated with higher hippocampal iron in men (r=-0.50, p=0.003) but not in women. Independent of gender, worse verbal working memory performance was associated with higher basal ganglia iron in IRON- group (r=-0.49, p=0.005) but not in the IRON+ group. Between-group interactions (p=0.006) were noted for both of these associations. No significant associations with white matter or processing speed were observed. The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Combining genetic and MRI biomarkers may provide opportunities to design primary prevention clinical trials that target high-risk groups.","Aged;Aging;Attention/physiology;Brain/anatomy & histology/ metabolism;Female;Histocompatibility Antigens Class I/ genetics;Humans;Image Processing, Computer-Assisted;Iron/ metabolism;Magnetic Resonance Imaging/methods;Male;Membrane Proteins/ genetics;Memory/ physiology;Middle Aged;Neuropsychological Tests;Relaxation;Sex Characteristics;Transferrin/ genetics;Verbal Learning","Bartzokis, G.;Lu, P. H.;Tingus, K.;Peters, D. G.;Amar, C. P.;Tishler, T. A.;Finn, J. P.;Villablanca, P.;Altshuler, L. L.;Mintz, J.;Neely, E.;Connor, J. R.",2011,Jun,10.1038/npp.2011.22,0,
5468,Lifespan trajectory of myelin integrity and maximum motor speed,"Objective: Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity. Methods: A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R2)) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N=72) between 23 and 80 years of age. To assess specificity, R2 of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured. Results: FLwm R2 and FTS measures were significantly correlated (r=.45, p<0001) with no association noted in the early-myelinating region (splenium). Both FLwm R2 and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter. Conclusions: The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R2 contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines. © 2008 Elsevier Inc.",biological marker;myelin;action potential;adult;age distribution;aged;article;cognition;controlled study;corpus callosum;finger tapping speed;frontal lobe;human;human experiment;human tissue;image analysis;in vivo study;male;motor performance;myelination;normal human;nuclear magnetic resonance imaging;priority journal;protein content;relaxation time;sensitivity and specificity;splenium;white matter,"Bartzokis, G.;Lu, P. H.;Tingus, K.;Mendez, M. F.;Richard, A.;Peters, D. G.;Oluwadara, B.;Barrall, K. A.;Finn, J. P.;Villablanca, P.;Thompson, P. M.;Mintz, J.",2010,,,0,
5469,Human brain myelination and amyloid beta deposition in Alzheimer's disease,"We hypothesized that myelin breakdown in vulnerable late-myelinating regions releases oligodendrocyte- and myelin-associated iron that promotes amyloid beta (A beta) oligomerization, its associated toxicity, and the deposition of oligomerized A beta and iron in neuritic plaques observed in Alzheimer's disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of A beta deposits in humans. The data show that in AD, radiolabeled ligands detect A beta deposition in a distribution that matches the map of late-myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind A beta in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the ""myelin model"" are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron.",,"Bartzokis, G.;Lu, P. H.;Mintz, J.",2007,Apr,10.1016/j.jalz.2007.01.019,0,
5470,Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia,"BACKGROUND: Age-related myelin breakdown is most evident in later-myelinating white matter (LMwm) brain regions. This process might degrade cognitive processing speed (CPS) underlying age-related cognitive decline and the predominance of age as a risk factor for Alzheimer's disease (AD). Apolipoprotein E (ApoE) 4 allele is the second most important AD risk factor. We tested the hypothesis that ApoE4 accelerates age-related slowing in CPS through the process of myelin breakdown. METHODS: Calculated transverse relaxation rates (R(2)), an indirect magnetic resonance imaging measure of myelin breakdown in LMwm, and measures of CPS were obtained in 22 ApoE4+ and 80 ApoE4-, healthy ""younger-old"" individuals. To assess specificity, contrasting early-myelinating white matter region and memory task were also examined. RESULTS: The CPS versus LMwm R(2) remained significant in the ApoE4+ group even after age was statistically adjusted (r = .65, p = .001) and differed from the correlation observed in the ApoE4- group (Fisher's z test = 3.22, p < .002). No significant associations were observed with the contrast region and memory task in either ApoE subgroup. CONCLUSIONS: A specific association between CPS and myelin breakdown in LMwm exists in asymptomatic ""younger-old"" individuals at increased genetic risk for AD. Although inferences of change over time and causality are limited by the cross-sectional study design, this finding lends support to the hypotheses that myelin breakdown underlies age-related slowing in CPS and that by altering the trajectory of myelin breakdown, ApoE alleles shift the age at onset of cognitive decline. Combined use of biomarkers and CPS measures might be useful in developing and targeting primary prevention treatments for AD.","Aged;Aged, 80 and over;Aging;Apolipoproteins E/ genetics;Chi-Square Distribution;Cognition Disorders/diagnosis/ genetics/ pathology;Dementia/ physiopathology/psychology;Female;Genetic Predisposition to Disease/genetics;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Myelin Sheath/pathology/ physiology;Neuropsychological Tests","Bartzokis, G.;Lu, P. H.;Geschwind, D. H.;Tingus, K.;Huang, D.;Mendez, M. F.;Edwards, N.;Mintz, J.",2007,Dec 15,10.1016/j.biopsych.2007.03.024,0,
5471,Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia,"CONTEXT: Apolipoprotein E (APOE) genotype is the most influential Alzheimer disease (AD) risk factor after advanced age. The APOE4 alleles decrease and the APOE2 alleles increase age at onset of AD. Human and nonhuman primate data suggest that in midlife, the structural integrity of myelin sheaths begins breaking down, with an accelerating age-related trajectory most evident in the brain's later-myelinating association regions. This may result in a progressive ""disconnection"" of widely distributed neural networks that may underlie the age risk factor for AD. OBJECTIVE: To assess, using magnetic resonance imaging, whether the shift in age at onset of AD observed with the APOE genotype is associated with the trajectory of age-related myelin breakdown. DESIGN: Cross-sectional. SETTING: Metropolitan university medical center. PARTICIPANTS: Healthy individuals (N = 104) aged 55 to 75 years who underwent genotyping for APOE. MAIN OUTCOME MEASURES: Calculated transverse relaxation rates, an indirect measure of white matter structural integrity, for late-myelinating frontal lobe white matter (Fwm) and early- and later-myelinating regions of the corpus callosum, the splenium (Swm) and the genu (Gwm). RESULTS: The presence of the protective APOE2 allele was associated with significantly higher relaxation rates in Fwm and Gwm but not in Swm. Furthermore, APOE status impacted the trajectory of age-related myelin breakdown in late-myelinating regions (Fwm and Gwm) but not in Swm. In Fwm and Gwm, APOE4+ individuals had a steeper slope of decline in relaxation rates with age than APOE2+ individuals; those with APOE3/3 alleles had an intermediate slope. CONCLUSIONS: In later-myelinating regions, the severity and rate of myelin breakdown in healthy older individuals are associated with APOE status and support the hypothesis that this process may contribute to age at onset of AD. Combining APOE status with noninvasive measures of myelin breakdown may be useful in assessing treatment strategies for the primary prevention of AD.",Age Factors;Age of Onset;Aged;Alzheimer Disease/diagnosis/ genetics/ pathology;Apolipoproteins E/ genetics;Cognition Disorders/diagnosis/ genetics/ pathology;Corpus Callosum/ pathology;Cross-Sectional Studies;Disease Progression;Female;Frontal Lobe/ pathology;Genetic Predisposition to Disease/genetics;Genotype;Humans;Magnetic Resonance Imaging;Male;Myelin Sheath/pathology/ physiology;Primary Prevention/methods;Prognosis,"Bartzokis, G.;Lu, P. H.;Geschwind, D. H.;Edwards, N.;Mintz, J.;Cummings, J. L.",2006,Jan,10.1001/archpsyc.63.1.63,0,
5472,White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study,"BACKGROUND: Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about the age of 44.6 years and then declines. Postmortem evidence indicates that the structural integrity of myelin sheaths deteriorates during normal aging, especially in late myelinating regions such as the frontal lobes. OBJECTIVES: To assess the integrity of FLWM by magnetic resonance imaging and, thus, to provide an important index of brain aging and its relationship to Alzheimer disease (AD). DESIGN: Cross-sectional study. SETTING: Two metropolitan university hospitals and AD research centers. PARTICIPANTS: Two hundred fifty-two healthy adults (127 men and 125 women), aged 19 to 82 years, and 34 subjects with AD (16 men and 18 women), aged 59 to 85 years. MAIN OUTCOME MEASURE: Calculated transverse relaxation rate (R( 2)) of the FLWM (an indirect measure of the structural integrity of white matter). RESULTS: As expected from prior imaging data on FLWM volume, the quadratic function best represented the relationship between age and the FLWM R(2) (P<.001). In healthy individuals, the FLWM R(2) increased until the age of 38 years and then declined markedly with age. The R( 2) of subjects with AD was significantly lower than that of a group of healthy control subjects who were of similar age and sex (P<.001). CONCLUSIONS: The R(2) changes in white matter suggest that the healthy adult brain is in a constant state of change, roughly defined as periods of maturation continuing into middle age followed by progressive loss of myelin integrity. Clinically diagnosed AD is associated with more severe myelin breakdown. Noninvasive measures, such as the determination of the R(2), may have the potential to track prospectively the trajectory of deteriorating white matter integrity during normal aging and the development of AD and, thus, may be a useful marker for medication development aimed at the prevention of AD.","Adult;Aged;Aged, 80 and over;Aging/ pathology;Alzheimer Disease/ pathology;Cross-Sectional Studies;Female;Frontal Lobe/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Regression Analysis","Bartzokis, G.;Cummings, J. L.;Sultzer, D.;Henderson, V. W.;Nuechterlein, K. H.;Mintz, J.",2003,Mar,,0,
5473,Increased basal ganglia iron levels in Huntington disease,"OBJECTIVE: To quantify in vivo brain ferritin iron levels in patients with Huntington disease (HD) and normal control subjects. DESIGN AND SUBJECTS: A magnetic resonance imaging method that can quantify ferritin iron levels with specificity in vivo was employed to study 11 patients with HD and a matched group of 27 normal controls. Three basal ganglia structures (caudate, putamen, and globus pallidus) and 1 comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia iron levels were significantly increased (P<.002) in patients with HD, and this increase occurred early in the disease process. This was not a generalized phenomenon, as white matter iron levels were lower in patients with HD. CONCLUSIONS: The data suggest that increased iron levels may be related to the pattern of neurotoxicity observed in HD. Reducing the oxidative stress associated with increased iron levels may offer novel ways to delay the rate of progression and possibly defer the onset of HD.",Adult;Aged;Basal Ganglia/ chemistry/pathology;Disease Progression;Female;Ferritins/ analysis;Humans;Huntington Disease/ metabolism/pathology;Male;Middle Aged;Neurotoxins/pharmacology;Oxidative Stress,"Bartzokis, G.;Cummings, J.;Perlman, S.;Hance, D. B.;Mintz, J.",1999,May,,0,
5474,Subjective memory complaints in community dwelling healthy older people: the influence of brain and psychopathology,"OBJECTIVES: Subjective memory complaints (SMC) are common. We aimed to characterize the relationship between psychiatric illness and white matter disease to SMC in a sample of healthy older people. MEASUREMENTS: Cognitively normal subjects between 55 and 90 years had age-adjusted and education-adjusted Consortium to Establish a Registry for Alzheimer's disease (CERAD) scores </=1.5 SD from standard mean. ApoE genotyping was performed using polymerase chain reaction. Sixty subjects (30 SMC, 30 controls) underwent 3T MRI, which was rated by two raters blinded to the diagnosis, for periventricular (PVH) and deep white matter hyperintensities (DWMH) using the Fazekas scale. Subjective memory was assessed by asking the participant, Do you feel like your memory or thinking is becoming worse? RESULTS: Two hundred and fifteen volunteers were assessed. Ninety-six were cognitively normal (mean age 62.5 years). SMC were reported by 52/96 subjects (54%). These were compared with subjects who denied SMC. Participants with a history of depression or anxiety were more likely to have SMC (p = 0.02). The frequency distribution of ApoE4 allele and CERAD scores were similar. White matter load was similar (p </= 0.47), with a high prevalence of PVH and DWMH seen (100% and 88% of scans, respectively). CONCLUSION: Both SMC and white matter disease were common. SMC were associated with a history of depression or anxiety but not with white matter disease. Evaluation for a history of depression and anxiety in people with SMC is supported by these findings.","Age Factors;Aged;Aged, 80 and over;Apolipoproteins E/genetics;Brain/*pathology;Depressive Disorder/genetics/*psychology;Female;Humans;Ireland;Magnetic Resonance Imaging;Male;Memory Disorders/genetics/*pathology/*psychology;Middle Aged;Neuropsychological Tests","Bartley, M.;Bokde, A. L.;Ewers, M.;Faluyi, Y. O.;Tobin, W. O.;Snow, A.;Connolly, J.;Delaney, C.;Coughlan, T.;Collins, D. R.;Hampel, H.;O'Neill, D.",2012,Aug,10.1002/gps.2794,0,
5475,"Interactive segmentation of cerebral gray matter, white matter, and CSF: photographic and MR images","Digital photography of postmortem brain slices was compared with magnetic resonance imaging (MRI) for morphological analysis of human brain atrophy. In this study, we used two human brains obtained at autopsy: a cognitively defined nondemented control (70-yr-old male) and a demented Alzheimer's disease (AD) subject (82-yr-old female). For each of two brains, interactive manual image segmentation was performed by two observers on two image sets: (a) four coronal T1-weighted MR images (5 mm slices); and (b) four digitized photographic images from comparable rostrocaudal levels. Microcomputer image analysis software was used to measure the areas of three segmented cerebral compartments--gray matter (GM), white matter (WM) and CSF--for both image types. Resegmentation error was defined as the absolute difference between the areas derived from two segmentation trials divided by the value from trial 1 and multiplied by 100. This yielded the percent difference between the area measurements from the two trials. We found intra-observer agreement was better (error rates 1-18%) than inter-observer agreement (3-70%) with best agreement for WM and least for CSF, the smallest object class. MRI overestimated GM area relative to digitized photographs in the control but not the AD brain. The results define limitations of manual image segmentations and comparison of MRI with pathologic section photographic images.","Aged;Aged, 80 and over;Alzheimer Disease/cerebrospinal fluid/pathology;Atrophy;Brain/ anatomy & histology/pathology;Cerebrospinal Fluid;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Microcomputers;Microtomy;Observer Variation;Photography;Reproducibility of Results;Signal Processing, Computer-Assisted;Software","Bartlett, T. Q.;Vannier, M. W.;McKeel, D. W., Jr.;Gado, M.;Hildebolt, C. F.;Walkup, R.",1994,Nov-Dec,,0,
5476,"A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia","This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761 (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed.","Alzheimer Disease [drug therapy];Cognition [drug effects];Dementia, Multi-Infarct [drug therapy];Disease Progression;Double-Blind Method;Flavonoids [pharmacology] [therapeutic use];Ginkgo biloba [therapeutic use];Neuroprotective Agents [pharmacology] [therapeutic use];Phytotherapy;Plant Extracts [therapeutic use];Plants, Medicinal;Severity of Illness Index;Treatment Outcome;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Hs-handsrch: sr-compmed: sr-dementia","Bars, P. L.;Kieser, M.;Itil, K. Z.",2000,,17242,0,
5477,In vivo characterization of chronic traumatic encephalopathy using F-18 FDDNP PET brain imaging,"Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/radionuclide imaging;Amygdala/microbiology/pathology;Autopsy;Brain/ pathology/ radionuclide imaging;Brain Injury, Chronic/ radionuclide imaging;Case-Control Studies;Demography;Humans;Male;Mesencephalon/microbiology/pathology;Middle Aged;Nitriles;Positron-Emission Tomography","Barrio, J. R.;Small, G. W.;Wong, K. P.;Huang, S. C.;Liu, J.;Merrill, D. A.;Giza, C. C.;Fitzsimmons, R. P.;Omalu, B.;Bailes, J.;Kepe, V.",2015,Apr 21,10.1073/pnas.1409952112,0,
5478,Tissue segmentation on MR images of the brain by possibilistic clustering on a 3D wavelet representation,"An algorithm for the segmentation of a single sequence of three-dimensional magnetic resonance (MR) images into cerebrospinal fluid, gray matter, and white matter classes is proposed. This new method is a possibilistic clustering algorithm using the fuzzy theory as frame and the wavelet coefficients of the voxels as features to be clustered. Fuzzy logic models the uncertainty and imprecision inherent in MR images of the brain, while the wavelet representation allows for both spatial and textural information. The procedure is fast, unsupervised, and totally independent of any statistical assumptions. The method is tested on a phantom image, then applied to normal and Alzheimer's brains, and finally compared with another classic brain tissue segmentation method, affording a relevant classification of voxels into the different tissue classes.","Adult;Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/diagnosis;Brain/ pathology;Cluster Analysis;Female;Fuzzy Logic;Humans;Image Interpretation, Computer-Assisted;Image Processing, Computer-Assisted/ statistics & numerical data;Logistic Models;Magnetic Resonance Imaging/ statistics & numerical data;Male;Middle Aged;Reference Values","Barra, V.;Boire, J. Y.",2000,Mar,,0,
5479,Semiautomated detection of cerebral microbleeds in magnetic resonance images,"Cerebral microbleeds (CMBs) are increasingly being recognized as an important biomarker for neurovascular diseases. So far, all attempts to count and quantify them have relied on manual methods that are time-consuming and can be inconsistent. A technique is presented that semiautomatically identifies CMBs in susceptibility weighted images (SWI). This will both reduce the processing time and increase the consistency over manual methods. This technique relies on a statistical thresholding algorithm to identify hypointensities within the image. A support vector machine (SVM) supervised learning classifier is then used to separate true CMB from other marked hypointensities. The classifier relies on identifying features such as shape and signal intensity to identify true CMBs. The results from the automated section are then subject to manual review to remove false-positives. This technique is able to achieve a sensitivity of 81.7% compared with the gold standard of manual review and consensus by multiple reviewers. In subjects with many CMBs, this presents a faster alternative to current manual techniques at the cost of some lost sensitivity. © 2011 Elsevier Inc.",,"Barnes, S. R. S.;Haacke, E. M.;Ayaz, M.;Boikov, A. S.;Kirsch, W.;Kido, D.",2011,July,,0,
5480,"Head size, age and gender adjustment in MRI studies: A necessary nuisance?","Imaging studies of cerebral volumes often adjust for factors such as age that may confound between-subject comparisons. However the use of nuisance covariates in imaging studies is inconsistent, which can make interpreting results across studies difficult. Using magnetic resonance images of 78 healthy controls we assessed the effects of age, gender, head size and scanner upgrade on region of interest (ROI) volumetry, cortical thickness and voxel-based morphometric (VBM) measures. We found numerous significant associations between these variables and volumetric measures: cerebral volumes and cortical thicknesses decreased with increasing age, men had larger volumes and smaller thicknesses than women, and increasing head size was associated with larger volumes. The relationships between most ROIs and head size volumes were non-linear. With age, gender, head size and upgrade in one model we found that volumes and thicknesses decreased with increasing age, women had larger volumes than men (VBM, whole-brain and white matter volumes), increasing head size was associated with larger volumes but not cortical thickness, and scanner upgrade had an effect on thickness and some volume measures. The effects of gender on cortical thickness when adjusting for head size, age and upgrade showed some non-significant effect (women > men), whereas the independent effect of head size showed little pattern. We conclude that age and head size should be considered in ROI volume studies, age, gender and upgrade should be considered for cortical thickness studies and all variables require consideration for VBM analyses. Division of all volumes by head size is unlikely to be adequate owing to their non-proportional relationship. © 2010 Elsevier Inc.",,"Barnes, J.;Ridgway, G. R.;Bartlett, J.;Henley, S. M. D.;Lehmann, M.;Hobbs, N.;Clarkson, M. J.;MacManus, D. G.;Ourselin, S.;Fox, N. C.",2010,December,,0,
5481,Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls,"This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Abeta1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Abeta1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Abeta1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Abeta1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages.",Aged;Alzheimer Disease/cerebrospinal fluid/*pathology;Amyloid beta-Peptides/cerebrospinal fluid;Atrophy;Biomarkers/cerebrospinal fluid;Brain/metabolism/*pathology;Cerebral Arteries/*pathology;Disease Progression;Female;*Functional Neuroimaging;Humans;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/cerebrospinal fluid/pathology;Peptide Fragments/cerebrospinal fluid;tau Proteins/cerebrospinal fluid,"Barnes, J.;Carmichael, O. T.;Leung, K. K.;Schwarz, C.;Ridgway, G. R.;Bartlett, J. W.;Malone, I. B.;Schott, J. M.;Rossor, M. N.;Biessels, G. J.;DeCarli, C.;Fox, N. C.",2013,Aug,10.1016/j.neurobiolaging.2013.02.003,0,
5482,Predicting risk of dementia in older adults: The late-life dementia risk index,"OBJECTIVE: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years. METHODS: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients. RESULTS: Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores. CONCLUSIONS: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.","Age Factors;Aged;Aged, 80 and over;Alcohol Drinking/epidemiology;Apolipoprotein E4/genetics;Body Mass Index;Carotid Stenosis/epidemiology;Cerebrum/pathology/physiopathology;Cognition Disorders/epidemiology;Cohort Studies;Coronary Artery Bypass/adverse effects;Dementia/*epidemiology/physiopathology;Female;Genetic Markers/genetics;*Health Status Indicators;Humans;Logistic Models;Male;Predictive Value of Tests;Risk Assessment/methods;Risk Factors;Risk Reduction Behavior","Barnes, D. E.;Covinsky, K. E.;Whitmer, R. A.;Kuller, L. H.;Lopez, O. L.;Yaffe, K.",2009,Jul 21,10.1212/WNL.0b013e3181a81636,0,
5483,"Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study","CONTEXT: Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons. OBJECTIVES: To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease. DESIGN: Prospective, population-based, longitudinal study. SETTING: Random sample of adults 65 years or older recruited from 4 US communities. PARTICIPANTS: Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria. MAIN OUTCOME MEASURE: Diagnosis of MCI. RESULTS: Depressive symptoms at baseline were associated with increased risk of MCI (10.0%, 13.3%, and 19.7% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics. CONCLUSION: Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.","Aged;Cerebrovascular Disorders/diagnosis/epidemiology/etiology;Cognition Disorders/ diagnosis/epidemiology/etiology;Comorbidity;Dementia/ epidemiology/etiology;Dementia, Vascular/epidemiology/etiology;Depressive Disorder/ diagnosis/epidemiology;Female;Follow-Up Studies;Geriatric Assessment;Humans;Longitudinal Studies;Male;Prospective Studies;Psychiatric Status Rating Scales;Risk Factors;Sampling Studies;Vascular Diseases/complications/diagnosis/ epidemiology","Barnes, D. E.;Alexopoulos, G. S.;Lopez, O. L.;Williamson, J. D.;Yaffe, K.",2006,Mar,10.1001/archpsyc.63.3.273,0,
5484,Clinicoradiologic correlations of cerebral microbleeds in advanced age,"BACKGROUND AND PURPOSE: The presence of cerebral microbleeds has been associated with dementia and cognitive decline, although studies report conflicting results. Our aim was to determine the potential role of the presence and location of cerebral microbleeds in early stages of cognitive decline. MATERIALS AND METHODS: Baseline 3T MR imaging examinations including SWI sequences of 328 cognitively intact communitydwelling controls and 72 subjects with mild cognitive impairment were analyzed with respect to the presence and distribution of cerebral microbleeds. A neuropsychological follow-up of controls was performed at 18 months post inclusion and identified cases with subtle cognitive deficits were referred to as controls with a deteriorating condition. Group differences in radiologic parameters were studied by using nonparametric tests, 1-way analysis of variance, and Spearman correlation coefficients. RESULTS: Cerebral microbleed prevalence was similar in subjects with mild cognitive impairment and controls with stable and cognitively deteriorating conditions (25%-31.9%). In all diagnostic groups, lobar cerebral microbleeds were more common. They occurred in 20.1% of all cases compared with 6.5% of cases with deep cerebral microbleeds. None of the investigated variables (age, sex, microbleed number, location and depth, baseline Mini-Mental State Examination score, and the Fazekas score) were significantly associated with cognitive deterioration with the exception of education of >12 years showing a slight but significant protective effect (OR, 0.44; 95% CI, 0.22- 0.92; P=.028). The Mini-Mental State Examination and the Buschke total score were correlated with neither the total number nor lobar-versusdeep location of cerebral microbleeds. CONCLUSIONS: Cerebral microbleed presence, location, and severity are not related to the early stages of cognitive decline in advanced age.",aged;article;brain hemorrhage di [Diagnosis];cognitive defect;controlled clinical trial;controlled study;female;follow up;frontal lobe;human;major clinical study;male;mental deterioration;mild cognitive impairment;Mini Mental State Examination;neuropsychological test;nonparametric test;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;occipital lobe;parietal lobe;prevalence;prospective study;temporal lobe;nuclear magnetic resonance scanner ct [Clinical Trial];analysis of variance;brain hemorrhage;correlation coefficient;diagnosis related group;education;population based case control study,"Barnaure, I.;Montandon, M. L.;Rodriguez, C.;Herrmann, F.;Lovblad, K. O.;Giannakopoulos, P.;Haller, S.",2017,,,0,
5485,Pre- and post-mortem MR imaging of unsuspected multiple sclerosis in a patient with Alzheimer's disease,"A patient with the clinical diagnosis of Alzheimer's disease is presented in whom pre-mortem T(2)-weighted MRI revealed a periventricular white matter lesion. Postmortem T(2) weighted MRIs of the formalin fixed brain revealed the same white matter lesion. Microscopically, classical Alzheimer changes were found and, unsuspectedly the histopathological correlate of the white matter lesion proved to be an old, inactive, MS plaque. A similar lesion was discovered in the cervical myelum. These findings illustrate that T(2)- weighted post-mortem MRIs are highly comparable to pre-mortem images and that MRI is sensitive in detecting clinically silent white matter lesions. The histopathology of such lesions may also include MS plaques.",,"Barkhof, F.;Scheltens, P.;Kamphorst, W.",1993,1993,,0,
5486,Guidelines for brain imaging in vascular dementia clinical trials,"Imaging should be included in the workup of dementia patients and is mandatory for the diagnosis of vascular dementia (VaD). MRI is the preferred imaging modality and should include axial T2 and FLAIR, preferably accompanied by a 3D T1-weighted sequence in clinical trials to determine white-matter lesions, infarcts, lacunes, and atrophy. Gradient echo images are needed for microbleeds. Diagnostic criteria should be operationalized and validated visual rating scales are available. In clinical trials, standardized acquisition protocols and central data analysis are mandatory. More work is needed to determine the natural progression in VaD and the possible use of MRI-based outcome measures.","Aged;Brain/ pathology/ radiography;Clinical Trials as Topic;Dementia, Vascular/ diagnosis;Guidelines as Topic;Humans;Magnetic Resonance Imaging;Tomography, X-Ray Computed","Barkhof, F.",2003,,10.1017/s1041610203009323,0,
5487,AIDS dementia complex: evaluation with proton MR spectroscopic imaging,"PURPOSE: To investigate cerebral metabolic changes in acquired immunodeficiency syndrome dementia complex (ADC) with proton magnetic resonance (MR) spectroscopic imaging and compare the findings with those of conventional MR imaging. MATERIALS AND METHODS: Seven patients with ADC (all men; age range, 33-58 years; mean, 43 years) with human immunodeficiency virus (HIV) infection and seven age-matched volunteers without HIV infection underwent spectroscopic and conventional MR imaging. RESULTS: Patient spectra were characterized by reduced levels of N-acetyl aspartate and increased levels of choline in white-matter regions. Lactate was detected in the cerebrospinal fluid of five patients. Four patients with mild to moderate dementia had more extensive metabolic abnormalities than three patients with only mild neurocognitive changes. CONCLUSION: Proton MR spectroscopic imaging shows extensive metabolic changes and is more sensitive than conventional MR imaging in the detection of central nervous system involvement in ADC.",AIDS Dementia Complex/ diagnosis/metabolism;Adult;Aspartic Acid/analogs & derivatives/metabolism;Brain/ metabolism/pathology;Choline/metabolism;Humans;Lactates/cerebrospinal fluid;Lactic Acid;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Sensitivity and Specificity,"Barker, P. B.;Lee, R. R.;McArthur, J. C.",1995,Apr,10.1148/radiology.195.1.7892496,0,
5488,Differential diagnosis of dementing diseases,"Evaluation of the cognitively impaired patient necessitates documentation of dementia, with the help of standard and robust neuropsychological tests, followed by identification of focal, multi-focal, or subcortical neurological signs which help differentiate the most common dementing diseases. The usual diagnostic dilemma is to distinguish Alzheimer's disease from circulatory dementia. Until recently, Alzheimer's disease was considered a diagnosis of exclusion, with confirmation only by pathological examination. Invasive tests, such as lumbar puncture for protein markers or skin biopsy for genetic markers, may aid in the antemortem diagnosis of Alzheimer's. Noninvasively determined information which may provide diagnostic clues includes family history of dementia and fingerprint patterns. Circulatory dementia need not be confined to multi-infarct dementia, but may also include dementia accompanying cerebrovascular or cardiovascular disease. Features associated with circulatory dementia include remote history of urinary and gait disturbances, ear hair growth, and 'infarcts' on MRI of CTT. Although the significance of 'infarcts' on MRI is unclear, they are associated with high Hachinski ischemic score, hypertension, and cardiac arrhythmias. 'Infarcts' on MRI are more sensitive, but less specific, than 'infarcts' on CTT, in diagnosing circulatory dementia. Techniques of decision analysis can help determine the diagnostic utility of the Hachinski score and its components, as well as of imaging techniques and other diagnostic aids, in differential diagnosis. In drug trials for Alzheimer's, where maximum sensitivity in the diagnosis of circulatory dementia is needed to exclude inappropriate subjects, the MRI is the imaging procedure of choice. Conversely, drug trials for circulatory dementia should use the CTT to enhance specificity. In the absence of specific therapeutic intervention, either procedure may be used, as overall diagnostic utility of the CTT and MRI, as determined by the Brier score, is comparable.",,"Barclay, L.",1988,1988,,0,
5489,[The significance of cerebral white matter changes in CT images in Alzheimer's disease] Znaczenie zmian w istocie bialej mozgu w obrazie tomografii komputerowej w chorobie Alzheimera,"White matter changes in Alzheimer's disease patients were the subject of the study. One hundred and seventeen cases clinically diagnosed according to NINCDS-ADRDA criteria as probable Alzheimer's disease were assessed. In computer tomography two types of pathological changes were observed; the so called leucoaraiosis and the perivascular focal alterations. Leucoaraiosis appeared in 20% of cases and focal changes were visible only in 4 cases A significant correlation was found between the presence of leucoaraiosis and the age and the presence of coronary disease. Hypertension, diabetes and brain atrophy did not seem to influence the occurrence of white matter alterations of either type.","Aged;Alzheimer Disease/complications/ diagnostic imaging/ pathology;Brain/ diagnostic imaging/ pathology;Diabetes Complications;Female;Humans;Hypertension/complications;Male;Middle Aged;Tomography, X-Ray Computed","Barcikowska, M.;Golebiowski, M.;Pfeffer, A.",1997,Mar-Apr,,0,
5490,The significance of cerebral white matter changes in CT images in Alzheimer's disease,"White matter changes in Alzheimer's disease patients were the subject of the study. One hundred and seventeen cases clinically diagnosed according to NINCDS-ADRDA criteria as probable Alzheimer's disease were assessed. In computer tomography two types of pathological changes were observed; the so called leucoaraiosis and the perivascular focal alterations. Leucoaraiosis appeared in 20% of cases and focal changes were visible only in 4 cases A significant correlation was found between the presence of leucoaraiosis and the age and the presence of coronary disease. Hypertension, diabetes and brain atrophy did not seem to influence the occurrence of white matter alterations of either type.","Aged;Alzheimer Disease/complications/ pathology/ radiography;Brain/ pathology/ radiography;Diabetes Complications;Female;Humans;Hypertension/complications;Male;Middle Aged;Tomography, X-Ray Computed","Barcikowska, M.;Golebiowski, M.;Pfeffer, A.",1997,Mar-Apr,,0,
5491,"White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging","OBJECTIVES: Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. METHODS: Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI scanner in patients with dementia with Lewy bodies (consensus criteria; n=27, mean age=75.9 years), Alzheimer's disease (NINCDS/ADRDA; n=28, mean age=77.4 years), vascular dementia (NINDS/AIREN; n=25, mean age=76.8 years), and normal controls (n=26, mean age=76.2 years). Cognitive function, depressive symptoms, and psychotic features were assessed using a standardised protocol. Periventricular hyperintensities (PVHs), white matter hyperintensities (WMHs) and basal ganglia hyperintensities (BGHs) were visually rated blind to diagnosis using a semiquantitative scale. RESULTS: Periventricular hyperintensities were positively correlated with age and were more severe in all dementia groups than controls. Total deep hyperintensities scores (WMHs plus BGHs) were significantly higher in all dementia groups than controls and higher in patients with vascular dementia than those with dementia with Lewy bodies or Alzheimer's disease. In all patients with dementia, frontal WMHs were associated with higher depression scores and occipital WMHs were associated with an absence of visual hallucinations and delusions. CONCLUSION: In common with Alzheimer's disease and vascular dementia, PVHs and WMHs were significantly more extensive in dementia with Lewy bodies than in controls. This overlap between different dementias may reflect shared pathological mechanisms. The link between frontal WMHs and depression and the absence of occipital WMHs and psychotic symptoms has important implications for understanding the neurobiological basis of these symptoms.",Aged;Aging/ pathology;Alzheimer Disease/ pathology;Analysis of Variance;Brain/ pathology;Female;Humans;Lewy Bodies/ pathology;Magnetic Resonance Imaging;Male,"Barber, R.;Scheltens, P.;Gholkar, A.;Ballard, C.;McKeith, I.;Ince, P.;Perry, R.;O'Brien, J.",1999,Jul,,0,
5492,MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimer's disease,"The aim of the study was to examine the relationship between white matter changes on magnetic resonance imaging (MRI), brain atrophy and ventricular dilation in late-life dementias. T(1)-weighted, T(2)-weighted, and proton density MRI scans were acquired in subjects with Alzheimer's disease (AD, N=25) and dementia with Lewy bodies (DLB, N=27). Total brain and ventricular volumes were measured and white matter lesions rated using a semi-quantitative scale. Periventricular hyperintensities (PVH) were found to independently correlate with advancing age and increasing ventricular dilatation in all subjects. In contrast, deep white matter hyperintensities (DWMH) did not correlate with measures of brain atrophy, ventricular dilatation or age, but were associated with a history of hypertension. These findings support the hypothesis that PVH and DWMH are pathologically diverse and that white matter change in AD and DLB may be determined by similar processes. In particular, PVH appear to be linked to atrophic processes involving ventricular enlargement and DWMH to ischaemic risk factors.","Age Factors;Aged;Aged, 80 and over;Alzheimer Disease/complications/ pathology/physiopathology;Atrophy;Brain/ pathology;Cerebral Ventricles/pathology;Female;Gliosis;Humans;Hypertension/ complications;Lewy Body Disease/complications/ pathology/physiopathology;Magnetic Resonance Imaging;Male;Outpatients;Statistics, Nonparametric","Barber, R.;Gholkar, A.;Scheltens, P.;Ballard, C.;McKeith, I. G.;O'Brien, J. T.",2000,Oct,,0,
5493,"Apolipoprotein E epsilon4 allele, temporal lobe atrophy, and white matter lesions in late-life dementias","OBJECTIVE: To examine the relationship between the apolipoprotein E (APOE) epsilon4 genotype, medial temporal lobe atrophy, and white matter hyperintensities on magnetic resonance imaging in late-life dementias. DESIGN: Structural magnetic resonance imaging study using T2-weighted and proton density-weighted axial scans and T1-weighted coronal scans. SETTING: Community-dwelling population of elderly patients prospectively chosen from a clinical case register of consecutive referrals to old age psychiatry services. SUBJECTS: Twenty-five subjects with Alzheimer disease (by criteria of the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; mean age, 77.8 years), 22 subjects with dementia with Lewy bodies (consensus criteria; mean age, 77.2 years), and 24 subjects with vascular dementia (by criteria of the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences; mean age, 76.9 years) were selected. Subjects were well matched for age, sex, duration of illness, and cognitive function. MAIN OUTCOME MEASURES: The APOE genotype was determined using the polymerase chain reaction method, and medial temporal lobe atrophy and white matter hyperintensities (periventricular and deep white matter) were visually rated using standardized scales. RESULTS: In all subjects with dementia, no significant associations were noted between APOE epsilon4 status and medial temporal lobe atrophy (mean score: 0 epsilon4 = 4.5, 1 epsilon4 = 4.5, and 2 epsilon4 = 4.3; P = .90), periventricular hyperintensities (0 epsilon4 = 3.3, 1 epsilon4 = 3.1, and 2 epsilon4 = 2.9; P = .83), and white matter hyperintensities (0 epsilon4 = 5.3, 1 epsilon4 = 4.9, and 2 epsilon4 = 4.9; P = .79). CONCLUSIONS: The APOE epsilon4 allele does not determine medial temporal lobe atrophy or white matter lesions, as measured by magnetic resonance imaging in patients with Alzheimer disease, vascular dementia, or dementia with Lewy bodies. Although APOE epsilon4 may modify the risk for acquiring dementia, this finding provides further evidence that APOE epsilon4 does not influence pathological processes thereafter.",Age Factors;Aged;Alleles;Alzheimer Disease/ genetics/ pathology;Apolipoprotein E4;Apolipoproteins E/ genetics;Atrophy/pathology;Cerebral Ventricles/physiology;Female;Gene Expression/physiology;Genotype;Hippocampus/ pathology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Prospective Studies;Severity of Illness Index;Temporal Lobe/ pathology,"Barber, R.;Gholkar, A.;Scheltens, P.;Ballard, C.;McKeith, I. G.;Morris, C. M.;O'Brien, J. T.",1999,Aug,,0,
5494,Patterns of (11)C-PIB cerebral retention in mild cognitive impairment patients,"OBJECTIVE: To evaluate the patterns of cerebral cortical distribution of (11)C-PIB in patients with mild cognitive impairment (MCI). MATERIAL AND METHODS: The study included 69 patients (37 male, age range 42-79 years) with MCI, sub-classified as 53 with amnestic-MCI (A-MCI), and 16 with non-amnestic-MCI (NA-MCI). Patients underwent (11)C-PIB PET/CT scan 60min after intravenous injection of the radiotracer. A visual analysis of the images was performed by 2 experienced physicians. (11)C-PIB-positive studies were considered when gray matter uptake was equal to or greater than white matter. According to the regions involved, (11)C-PIB-positive studies were classified into A-pattern (predominant retention in frontal, anterior cingulate, lateral temporal, and basal ganglia) and B-pattern (generalized retention). RESULTS: Thirty-nine of the 69 (56%) patients with MCI showed (11)C-PIB retention. Of the 53 A-MCI patients, 36 (68%) showed (11)C-PIB retention. Eleven out of 36 (30%) positive scans in A-MCI patients showed A-pattern, and 25 out of 36 (70%) patients had a B-pattern. Positive (11)C-PIB was observed in 3 out of 16 (19%) patients with NA-MCI. Regional distribution in these 3 patients showed A-pattern in 1, and B-pattern in 2 patients. CONCLUSION: Cortical retention of (11)C-PIB was more frequent in A-MCI than in NA-MCI patients, and also B-pattern than A-pattern in the (11)C-PIB positive group. The recognition of (11)C-PIB distribution patterns allows MCI patients to be classified, and the A-pattern may offer a therapeutic window for potential future treatments.",,"Banzo, I.;Jimenez-Bonilla, J. F.;Martinez-Rodriguez, I.;Quirce, R.;de Arcocha-Torres, M.;Bravo-Ferrer, Z.;Lavado-Perez, C.;Sanchez-Juan, P.;Rodriguez, E.;Jimenez-Alonso, M.;Lopez-Defillo, J.;Carril, J. M.",2016,May-Jun,10.1016/j.remn.2015.09.008,0,
5495,Dementia following herpes zoster encephalitis,"We studied the rare case of an older adult with dementia following herpes zoster encephalitis (HZE). This 71-year-old woman presented to us approximately 1 year following resolution of a rapid-onset episode of HZE, and subsequently underwent neuropsychological and neuroimaging examinations. Cognitive assessment revealed impairments in general cognitive functioning, verbal and nonverbal memory, executive functions, speed of information processing, attention/working memory, and motor skills. The patient's neuroimaging data, when compared to a demographically similar healthy control sample (n = 9), demonstrated moderate central and perisylvian brain volume loss, several subcortical lesions in the white matter, and resting state whole brain and hippocampal hypoperfusion. These findings highlight neuropsychological changes evident in a dementia syndrome of this type, and they suggest that early identification and treatment of HZE has implications for the preservation of long-term cognitive functioning.",aged;article;brain;case report;dementia;female;herpes zoster encephalitis;human;magnetic resonance angiography;neuropsychological test;nuclear magnetic resonance imaging;pathology;psychological aspect;radiography;virology,"Bangen, K. J.;Delano-Wood, L.;Wierenga, C. E.;Stricker, N. H.;Hesselink, J. R.;Bondi, M. W.",2010,,,0,
5496,Bipolar disorder against a background of a rare vascular dementia,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare cause of vascular dementia which is underdiagnosed and whose prevalence is currently undetermined. Here, Drs Bangash and Saad describe a highly uncommon case of manic symptoms in CADASIL and the diagnostic criteria and clinical management for this condition.",aripiprazole;clopidogrel;Notch3 receptor;olanzapine;valproic acid;Addenbrookes Cognitive Examination Revised;adult;bipolar disorder;brain infarction;CADASIL;case report;cerebrovascular accident;chromosome 19p;computer assisted tomography;dementia assessment;female;gene;gene mutation;genetic analysis;grandiose delusion;human;mania;medical history;memory disorder;middle aged;migraine;Mini Mental State Examination;multiinfarct dementia;NOTCH3 gene;note;nuclear magnetic resonance imaging;pathogenesis;patient compliance;patient referral;priority journal;restlessness;transient ischemic attack;walking aid,"Bangash, A.;Saad, K.",2016,,,0,
5497,MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden,"Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment. We also hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with brain amyloid burden, as detected by amyloid positron emission tomography using 11C-Pittsburgh B compound (PiB-PET). Two hundred and twenty-six patients (Alzheimer's disease n = 110; subcortical vascular cognitive impairment n = 116) with standardized MRI and PiB-PET imaging were included. MRI-visible perivascular spaces were rated using a validated 4-point visual rating scale, and then categorized by severity ('none/mild', 'moderate' or 'frequent/ severe'). Univariable and multivariable regression analyses were performed. Those with Alzheimer's disease-related cognitive impairment were younger, more likely to have a positive PiB-PET scan and carry at least one apolipoprotein E ""4 allele; those with subcortical vascular cognitive impairment were more likely to have hypertension, diabetes mellitus, hyperlipidaemia, prior stroke, lacunes, deep microbleeds, and carry the apolipoprotein E ""3 allele. In adjusted analyses, the severity of MRI-visible perivascular spaces in the centrum semi-ovale was independently associated with clinically diagnosed Alzheimer's disease (frequent/severe grade odds ratio 6.26, 95% confidence interval 1.66-23.58; P = 0.017, compared with none/mild grade), whereas the severity of MRI-visible perivascular spaces in the basal ganglia was associated with clinically diagnosed subcortical vascular cognitive impairment and negatively predicted Alzheimer's disease (frequent/severe grade odds ratio 0.03, 95% confidence interval 0.00-0.44; P = 0.009, compared with none/mild grade). MRI-visible perivascular space severity in either location did not predict PiB-PET. These findings provide further evidence that the anatomical distribution of MRI-visible perivascular spaces may reflect the underlying cerebral small vessel disease. Using MRI-visible perivascular space location and severity together with other imaging markers may improve the diagnostic value of neuroimaging in memory clinic populations, in particular in differentiating between clinically diagnosed Alzheimer's and subcortical vascular cognitive impairment.",PET-CT scanner;Philips 3.0T Achieva;amyloid;apolipoprotein E3;apolipoprotein E4;Pittsburgh compound B;4 point visual rating scale;aged;allele;Alzheimer disease;article;basal ganglion;brain hemorrhage;case control study;cerebrovascular accident;cognitive defect;controlled study;diabetes mellitus;diagnostic test accuracy study;disease burden;disease severity;female;human;hyperlipidemia;hypertension;lacunar stroke;major clinical study;male;mild cognitive impairment;multiinfarct dementia;multivariate logistic regression analysis;neuroimaging;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;odds ratio;perivascular space;positron emission tomography-computed tomography;predictive value;priority journal;prospective study;rating scale;subcortex;vascular amyloidosis;Discovery STe,"Banerjee, G.;Kim, H. J.;Fox, Z.;Jäger, H. R.;Wilson, D.;Charidimou, A.;Na, H. K.;Na, D. L.;Seo, S. W.;Werring, D. J.",2017,,10.1093/brain/awx003,0,
5498,MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden,"Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment. We also hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with brain amyloid burden, as detected by amyloid positron emission tomography using 11C-Pittsburgh B compound (PiB-PET). Two hundred and twenty-six patients (Alzheimer's disease n = 110; subcortical vascular cognitive impairment n = 116) with standardized MRI and PiB-PET imaging were included. MRI-visible perivascular spaces were rated using a validated 4-point visual rating scale, and then categorized by severity ('none/mild', 'moderate' or 'frequent/severe'). Univariable and multivariable regression analyses were performed. Those with Alzheimer's disease-related cognitive impairment were younger, more likely to have a positive PiB-PET scan and carry at least one apolipoprotein E varepsilon4 allele; those with subcortical vascular cognitive impairment were more likely to have hypertension, diabetes mellitus, hyperlipidaemia, prior stroke, lacunes, deep microbleeds, and carry the apolipoprotein E varepsilon3 allele. In adjusted analyses, the severity of MRI-visible perivascular spaces in the centrum semi-ovale was independently associated with clinically diagnosed Alzheimer's disease (frequent/severe grade odds ratio 6.26, 95% confidence interval 1.66-23.58; P = 0.017, compared with none/mild grade), whereas the severity of MRI-visible perivascular spaces in the basal ganglia was associated with clinically diagnosed subcortical vascular cognitive impairment and negatively predicted Alzheimer's disease (frequent/severe grade odds ratio 0.03, 95% confidence interval 0.00-0.44; P = 0.009, compared with none/mild grade). MRI-visible perivascular space severity in either location did not predict PiB-PET. These findings provide further evidence that the anatomical distribution of MRI-visible perivascular spaces may reflect the underlying cerebral small vessel disease. Using MRI-visible perivascular space location and severity together with other imaging markers may improve the diagnostic value of neuroimaging in memory clinic populations, in particular in differentiating between clinically diagnosed Alzheimer's and subcortical vascular cognitive impairment.",Alzheimer's disease;amyloid PET;cerebral amyoid angiopathy;perivascular space;subcortical vascular cognitive impairment,"Banerjee, G.;Kim, H. J.;Fox, Z.;Jager, H. R.;Wilson, D.;Charidimou, A.;Na, H. K.;Na, D. L.;Seo, S. W.;Werring, D. J.",2017,Feb 17,,0,
5499,Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease,"BACKGROUND: Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. METHODS: We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. RESULTS: Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. DISCUSSION: We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.","Aged;Aging;Alzheimer Disease/*pathology;Amnesia/complications/*pathology;Atrophy;Brain/*pathology;Cognition Disorders/complications/*pathology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Nerve Fibers, Myelinated/*pathology","Balthazar, M. L.;Yasuda, C. L.;Pereira, F. R.;Pedro, T.;Damasceno, B. P.;Cendes, F.",2009,Apr,10.1111/j.1468-1331.2008.02408.x,0,
5500,Perivascular Spaces Segmentation in Brain MRI Using Optimal 3D Filtering,"Perivascular Spaces (PVS) are a feature of Small Vessel Disease (SVD), and are an important part of the brain's circulation and glymphatic drainage system. Quantitative analysis of PVS on Magnetic Resonance Images (MRI) is important for understanding their relationship with neurological diseases. In this work, we propose a segmentation technique based on the 3D Frangi filtering for extraction of PVS from MRI. We used ordered logit models and visual rating scales as alternative ground truth for Frangi filter parameter optimization and evaluation. We optimized and validated our proposed models on two independent cohorts, a dementia sample (N = 20) and patients who previously had mild to moderate stroke (N = 48). Results demonstrate the robustness and generalisability of our segmentation method. Segmentation-based PVS burden estimates correlated well with neuroradiological assessments (Spearman's rho = 0.74, p < 0.001), supporting the potential of our proposed method.",,"Ballerini, L.;Lovreglio, R.;Valdes Hernandez, M. D. C.;Ramirez, J.;MacIntosh, B. J.;Black, S. E.;Wardlaw, J. M.",2018,Feb 1,,0,
5501,NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia,"OBJECTIVE: To determine the utility of the neuroimaging component within the National Institute of Neurological Disorders and Stroke (NINDS) Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for vascular dementia for distinguishing between patients with and without dementia in the context of cerebrovascular disease. METHOD: One hundred twenty-five poststroke patients age > or =75 (27 with and 98 without poststroke dementia) from representative hospital-based stroke registers in the North East of England were evaluated using a 1.5 T MR scanner. The proportion of patients with and without poststroke dementia meeting the imaging component of the NINDS AIREN criteria was determined, and hippocampal atrophy (measured using the Schelten scale) was compared between the two groups. RESULTS: There were no significant differences between the patients with and without poststroke dementia on any criteria of the imaging parameters within the NINDS AIREN criteria. In addition, there were no significant differences in the number or size of cortical or subcortical infarcts between the two groups, with 13 patients without dementia having cortical infarcts >50 mm. Patients with dementia had greater hippocampal atrophy (right: Mann-Whitney U test, Z = 2.5, p = 0.01; left: Mann-Whitney U test, Z = 2.5, p = 0.01). CONCLUSION: The neuroimaging component of the NINDS AIREN criteria does not distinguish between older patients with and without poststroke dementia.","Aged;Aged, 80 and over;Atrophy;Cerebral Infarction/complications/pathology/ psychology;Cohort Studies;Dementia, Vascular/ diagnosis/etiology/pathology;England/epidemiology;Female;Hippocampus/ pathology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;National Institutes of Health (U.S.);Neuropsychological Tests;Neurosciences;Severity of Illness Index;Single-Blind Method;Societies, Medical;United States","Ballard, C. G.;Burton, E. J.;Barber, R.;Stephens, S.;Kenny, R. A.;Kalaria, R. N.;O'Brien, J. T.",2004,Sep 28,,0,
5502,"Neurocardiovascular instability, hypotensive episodes, and MRI lesions in neurodegenerative dementia","We investigated whether carotid sinus hypersensitivity (CSH) and orthostatic hypotension (OH) were associated with a greater severity of hyperintensities on MRI scan in 30 patients with neurodegenerative dementia (17 dementia with Lewy bodies, 13 Alzheimer's disease), who had a detailed evaluation of OH and CSH during active standing and head-up tilt. Patients also underwent a 1.0 Tesla MRI scan, from which hyperintensities were rated on a standardized scale. A blood pressure (BP) drop > 30 mm Hg during carotid sinus massage or active standing was significantly associated with the severity of MRI hyperintensities in the deep white matter (OR 10.0, 95%; CI 1.8-55.7) and in the basal ganglia (OR 11.0, 95%; CI 1.2-99.5) but not in periventricular areas (OR 1.4, 95%; CI 0.3-1.8). Patients with the cardio-inhibitory form of CSH with the largest BP drops were the most at risk. Further longitudinal studies need to investigate the direction of causality to determine whether CSH or OH predispose to MRI hyperintensities and accelerate cognitive decline.","Aged;Alzheimer Disease/complications/pathology/*physiopathology;Basal Ganglia/pathology;Blood Pressure;Brain/*pathology;Carotid Sinus/*physiopathology;Female;Humans;*Hypotension, Orthostatic;Lewy Body Disease/complications/pathology/*physiopathology;Magnetic Resonance Imaging;Male","Ballard, C.;O'Brien, J.;Barber, B.;Scheltens, P.;Shaw, F.;McKeith, I.;Kenny, R. A.",2000,Apr,,0,
5503,"White matter lesions, dementia, and ischemic axonopathy",,brain atrophy;brain perfusion;cognitive defect;cohort analysis;dementia;hippocampus;human;hypertension;hypotension;ischemic axonopathy;letter;leukoaraiosis;neocortex;neuropathy;nuclear magnetic resonance imaging;pathophysiology;perikaryon;priority journal;white matter;white matter lesion,"Ball, M. J.",2003,,,0,
5504,Clinical and neuropsychological rating scales for differential diagnosis of dementias,"Clinical and neuropsychological rating scales were used in two studies of patients. The first one included 20 patients with progressive dementia and was divided into two groups according to their ischemic score evaluation and ancillary examinations (EEG, cerebral evoked potentials, CT scan, Doppler, xenon-133 clearance). The first group consisted of 10 patients with primary degenerative dementia of the Alzheimer type (SDAT) (n = 10). The second group included 10 patients with dementia caused by multi-infarction (MID). The second study included 18 patients with a confusional state, examined repeatedly for 1-6 months afterwards. The clinical and neuropsychological procedure consisted of a multi-dimensional assessment including 8 rating scales. A significant difference was found in the overall clinical and neuropsychological profile of patients with SDAT and MID. Cognitive functions were homogeneously impaired in the group of SDAT patients and heterogeneously in the group of MID patients. In chronic confusional states the overall profile was similar to that of the group of MID patients. Further reassessment showed a normalization in 9 patients, a vascular MID profile in 6 cases, an SDAT profile in 3 cases, and an undifferentiated one in 2 cases. Reversibility of the confusional state might be predicted at the onset of the cognitive disorder by history-taking and evaluation of the ischemic score.","Aged;Alzheimer Disease/diagnosis;Dementia/*diagnosis;Diagnosis, Differential;Female;Humans;Longitudinal Studies;Male;Neurologic Examination;Psychiatric Status Rating Scales","Baldy-Moulinier, M.;Valmier, J.;Touchon, J.;Rondouin, G.;Brun, M.",1986,,,0,
5505,Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome,"White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN-related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.","olanzapine;phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase;adolescent;adult;Alexander disease;apraxia;article;attention deficit disorder;autism;CADASIL;child;clinical article;controlled study;developmental delay;disease association;disease course;dysdiadochokinesis;dysmetria;fasciculation;female;gait disorder;gene mutation;genetic screening;genetic variability;hallucination;hamartoma;hereditary tumor syndrome;hip dysplasia;human;hypoglycemia;infant;intelligence;Lhermitte Duclos disease;macrocephaly;male;Marfan syndrome;middle aged;motor dysfunction;multiple sclerosis;neurologic examination;nuclear magnetic resonance imaging;nystagmus;obsessive compulsive disorder;oculomotor apraxia;phenotype;preschool child;priority journal;PTEN gene;PTEN hamartoma tumor syndrome;school child","Balci, T. B.;Davila, J.;Lewis, D.;Boafo, A.;Sell, E.;Richer, J.;Nikkel, S. M.;Armour, C. M.;Tomiak, E.;Lines, M. A.;Sawyer, S. L.",2018,,10.1002/ajmg.b.32610,0,
5506,A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging,"Background/objectives Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Methods Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Results Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p<0.05) differ between the groups. Conclusion Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes.",,"Balachandar, R.;John, J. P.;Saini, J.;Kumar, K. J.;Joshi, H.;Sadanand, S.;Aiyappan, S.;Sivakumar, P. T.;Loganathan, S.;Varghese, M.;Bharath, S.",2014,1,,0,
5507,"Lymphomatosis cerebri presenting as a rapidly progressive dementia: Clinical, neuroimaging and pathologic findings","Primary central nervous system lymphoma (PCNSL) usually presents with clinical and neuroimaging findings consistent with single or multiple intracranial mass lesions. On cranial magnetic resonance imaging (MRI), such lesions are nearly always contrast enhancing, reflecting disruption of the blood-brain barrier at the site of tumor nodules. We describe 2 cases from the UCLA Medical Center who developed a rapidly progressive dementia due to extensive gray and white matter cerebral lesions involving much of the brain. In the patient who came to autopsy, widely infiltrating, focally necrotic B-cell plasmacytoid lymphoma was noted throughout the cerebral neuraxis. MRI findings in case 2 were consistent with diffuse lymphomatous brain infiltration without mass lesions, which was biopsy proven. We conclude that PCNSL may occur in a diffusely infiltrating form which may occur without MRI evidence of mass lesions or blood-brain barrier compromise. We refer to this entity as 'lymphomatosis cerebri' and add it to the differential diagnosis of a rapidly progressive dementia.",,"Bakshi, R.;Mazziotta, J. C.;Mischel, P. S.;Jahan, R.;Seligson, D. B.;Vinters, H. V.",1999,1999,,0,
5508,The Effect of Central Nervous System Penetration Effectiveness of Highly Active Antiretroviral Therapy on Neuropsychological Performance and Neuroimaging in HIV Infected Individuals,"The incidence of HIV-associated dementia has been greatly reduced in the era of highly active antiretroviral therapy (HAART); however milder forms of cognitive impairment persist. It remains uncertain whether HAART regimens with a high degree of central nervous system penetration effectiveness (CPE) exert beneficial neurological outcomes in HIV-infected (HIV+) individuals on stable treatment. Sixty-four HIV-infected adults on HAART were assigned a CPE score using a published ranking system and divided into high (≥7; n = 35) and low (<7; n = 29) CPE groups. All participants completed neuropsychological testing in addition to structural neuroimaging. Neuropsychological tests included measures known to be sensitive to HIV with values converted into standardized scores (NPZ-4) based on published normative scores. A semi-automated methodology was utilized to assess brain volumetrics within cortical (grey and white matter) and subcortical (thalamus, caudate, putamen) regions of interest. Analyses assessed NPZ-4 and brain volumetric differences between HIV+ individuals with high and low CPE scores. No significant differences in brain integrity were observed between the two groups. Long-term HAART regimens with a high degree of CPE were not associated with significantly improved neuropsychological or neuroimaging outcomes in HIV+ adults. Results suggest that alternate mechanisms may potentially contribute to better neurological outcomes in the era of HAART.",adult;article;brain size;CD4 lymphocyte count;central nervous system;disease course;drug efficacy;drug penetration;ethnicity;female;functional neuroimaging;highly active antiretroviral therapy;human;Human immunodeficiency virus infection;major clinical study;male;neuropsychological test;outcome assessment;priority journal;scoring system;virus load,"Baker, L. M.;Paul, R. H.;Heaps-Woodruff, J. M.;Chang, J. Y.;Ortega, M.;Margolin, Z.;Usher, C.;Basco, B.;Cooley, S.;Ances, B. M.",2015,,,0,
5509,Correlation of cognition and SPECT perfusion: easy Z score and SPM analysis of a pilot sample with cerebral small vessel disease,"BACKGROUND/AIMS: To associate neuropsychology test performance with perfusion on single-photon emission computed tomography (SPECT) among 12 patients with cerebral small vessel disease. METHODS: The easy Z score imaging system (eZIS) was used to compare patient images to those of normal controls. Scores from neuropsychological tests commonly used to screen for dementia were associated with SPECT resting perfusion image values using the statistical parametric mapping (SPM) program. RESULTS: Immediate Memory and Delayed Memory index scores, as well as memory subtests of the Repeatable Battery for Assessment of Neuropsychological Status showed cluster- and voxelwise positive correlations with hypoperfusion in frontal, temporal and cerebellar regions. Negative correlations, primarily in frontal regions, were interpreted as compensatory hyperperfusion. CONCLUSION: eZIS and SPM analyses of SPECT images showed perfusion correlations with neuropsychological tests with small vessel disease.","Activities of Daily Living;Aged;Aged, 80 and over;Cerebral Cortex/physiopathology/radionuclide imaging;Cerebral Small Vessel Diseases/complications/ diagnosis;Cognition Disorders/complications/ diagnosis;Female;Humans;Male;Memory Disorders/complications/diagnosis;Middle Aged;Neuropsychological Tests;Pilot Projects;Tomography, Emission-Computed, Single-Photon","Baker, J. G.;Williams, A. J.;Wack, D. S.;Miletich, R. S.",2013,,10.1159/000339587,0,
5510,"Cerebral small vessel disease: cognition, mood, daily functioning, and imaging findings from a small pilot sample","Cerebral small vessel disease, a leading cause of cognitive decline, is considered a relatively homogeneous disease process, and it can co-occur with Alzheimer's disease. Clinical reports of magnetic resonance imaging (MRI)/computed tomography and single photon emission computed tomography (SPECT) imaging and neuropsychology testing for a small pilot sample of 14 patients are presented to illustrate disease characteristics through findings from structural and functional imaging and cognitive assessment. Participants showed some decreases in executive functioning, attention, processing speed, and memory retrieval, consistent with previous literature. An older subgroup showed lower age-corrected scores at a single time point compared to younger participants. Performance on a computer-administered cognitive measure showed a slight overall decline over a period of 8-28 months. For a case study with mild neuropsychology findings, the MRI report was normal while the SPECT report identified perfusion abnormalities. Future research can test whether advances in imaging analysis allow for identification of cerebral small vessel disease before changes are detected in cognition.",,"Baker, J. G.;Williams, A. J.;Ionita, C. C.;Lee-Kwen, P.;Ching, M.;Miletich, R. S.",2012,Jan,000333482,0,
5511,Activity/rest cycle and disturbances of structural backbone of cerebral networks in aging,"OBJECTIVE: Although aging is associated with alterations of both activity/rest cycle and brain structure, few studies have evaluated associations between these processes. The aim of this study was to examine relationship between activity/rest cycle quality and brain structural integrity in aging subjects by exploring both grey and white matter compartments. MATERIAL AND METHODS: Fifty-eight elderly subjects (76+/-0.5 years; 41% female) without dementia, sleep disorders and medications were included in the analysis. Actigraphy was used to measure parameters of activity/rest cycle (24-h amplitude, 24-h fragmentation and 24-h stability) and sleep (total sleep time and sleep fragmentation) over a minimal period of 5 days. Whole brain linear regression analyses were performed on grey matter volumes maps using voxel based morphometry and on white matter integrity using tract based statistics analyses. RESULTS: A lower 24-h amplitude and a higher sleep fragmentation were independently associated with a reduction of white matter integrity in models including age and gender as covariates. The association between 24-h amplitude and white matter integrity decreased but remained significant in a model accounted for sleep fragmentation, indicating a specific effect of 24-h cycle disturbances. No association with grey matter volumes was observed. CONCLUSION: In elderly, not only sleep but also 24-h cycle disturbances were associated with altered structural connectivity. This alteration of structural backbone networks related to activity/rest cycle disturbances in aging might constitute a cerebral frailty factor for the development of cognitive impairment.",Actigraphy;Activity/rest cycle;Aging;Diffusion tensor Imaging,"Baillet, M.;Dilharreguy, B.;Peres, K.;Dartigues, J. F.;Mayo, W.;Catheline, G.",2017,Feb 1,,0,
5512,Activity/rest cycle and disturbances of structural backbone of cerebral networks in aging,"OBJECTIVE: Although aging is associated with alterations of both activity/rest cycle and brain structures, few studies have evaluated associations between these processes. The aim of this study was to examine relationship between activity/rest cycle quality and brain structural integrity in aging subjects by exploring both grey and white matter compartments. MATERIAL AND METHODS: Fifty-eight elderly subjects (76 +/- 0.5 years; 41% female) without dementia, sleep disorders and medications were included in the analysis. Actigraphy was used to measure parameters of activity/rest cycle (24-h amplitude, 24-h fragmentation and 24-h stability) and sleep (total sleep time and sleep fragmentation) over a minimal period of 5 days. Whole brain linear regression analyses were performed on grey matter volumes maps using voxel based morphometry and on diffusion tensor parameters using tract based statistics. RESULTS: A lower 24-h amplitude and a higher sleep fragmentation were independently associated with a reduction of white matter integrity in models including age and gender as covariates. The association between 24-h amplitude and white matter integrity decreased but remained significant in a model accounted for sleep fragmentation, indicating a specific effect of 24-h cycle disturbances. No association with grey matter volumes was observed. CONCLUSION: In elderly, not only sleep but also 24-h cycle disturbances were associated with altered structural connectivity. This alteration of structural backbone networks related to activity/rest cycle disturbances in aging might constitute a cerebral frailty factor for the development of cognitive impairment.",Actigraphy;Activity/rest cycle;Aging;Diffusion Tensor Imaging,"Baillet, M.;Dilharreguy, B.;Peres, K.;Dartigues, J. F.;Mayo, W.;Catheline, G.",2016,Sep 21,10.1016/j.neuroimage.2016.09.051,0,5511
5513,Correlation study on vascular dementia and CT findings of subcortical ischemic infarcts,"Background: Subcortical ischemic infarct is commonly seen in cerebral vascular disease, but the relationship between its CT findings and vascular dementia still remains controversial. Objective: To explore the correlation of CT findings of subcortical ischemic vascular disease and vascular dementia. Design: A retrospective cross-sectional trial on the basis of diagnosis. Setting and Participants: Totally 128 patients confirmed by CT with subcortical multi-infarct were included from October 1999 to January 2002. Among them, 68 were female and 60 were male, aged from 54 to 89. Method: Comparative analysis was performed in the CT manifestations of the subcortical infarct patients with or without dementia. Main Outcome Measures: Locations, size and number of subcortical infarcts, degree of leukoaraiosis (LA) and index of brain atrophy. Results: Frequency, mean number and mean size of the infarcts in subcortex of lobus frontalis, anterior capsula interna, nucleus caudatus, anterior centrum semiovale, and anterior white matter around the body of ventriculus lateralis and thalamus were significantly larger in the dementia group than in the control group (P < 0.05). Leukoaraiosis (LA) of grade III or grade IV was more common in the dementia group than in control group(P < 0.05). Mean width of the cerebral sulci, mean width of sulcus lateralis, index of frontal eminence and VBR in the dementia group were significantly larger than in the control group(P < 0.05). In addition, unconditioned logistic regression analysis showed that the number of infarcts in subcortex of lobus frontalis and thalamus, size of infarcts in anterior white matter around the body of ventriculus lateralis and degree of leukoaraiosis and accompanied brain atrophy were significantly correlated with vascular dementia. Conclusion: Subcortical multi-infarct dementia may be closely correlated with the number, location and size of infarcts as well as the degree of leukoaraiosis and brain atrophy.",adult;aged;article;brain atrophy;brain infarction;brain infarction size;capsula interna;caudate nucleus;clinical feature;comparative study;computer assisted tomography;controlled study;correlation analysis;disease severity;female;frontal lobe;human;lateral brain ventricle;leukoaraiosis;logistic regression analysis;major clinical study;male;multiinfarct dementia;thalamus;white matter,"Bai, Z. L.;Zhang, Q. J.;Xue, G. Y.;Qi, N. X.",2004,,,0,
5514,MRI findings in subcortical ischemic vascular dementia,"Objective: To analyze the brain MRI findings in subcortical ischemic vascular dementia and to investigate their correlations with cognitive disorder. Methods: The brain MRI findings were compared between 25 dementia and 25 nondementia patients, all with subcortical ischemic vascular diseases. Results: (1)Incidences of infarction in caudate nucleus, lentiform nucleus, genu of internal capsule, thalamus, frontal and temporal subcortical white matter, anterior white matter around the body of lateral ventricle, and anterior and middle white matter of centrum semiovale were higher in dementia group than those in nondementia group (P<0.05); incidences of multiple cerebral infarction, bilateral and left cerebral infarction were higher in dementia group than those in nondementia group (P<0.05); (2) The total number of infarcts was higher in dementia group than that in nondementia group (P<0.001), and the former showed a larger number of infarct than the latter in caudate nucleus, lenticular nucleus, anterior internal capsule, external capsule, thalamus, frontal and temporal subcortical white matter, anterior and middle white matter around the body of lateral ventricle (P<0.05); (3) Dementia group showed larger total volume of infarct than nondementia group, especially in lentiform nucleus, anterior internal capsule, thalamus, frontal and temporal subcortical white matter, anterior white matter around the body of lateral ventricle and anterior and middle white matter of centrum semiovale (P<0.05); (4) Incidence of leukoaraiosis did not have difference between the 2 groups (P>0.05); the ratio of leukoaraiosis of 2 to 3 degree in dementia group was higher than that in nondementia group (P<0.001); (5) The index of cerebral atrophy in dementia group was significantly higher than that in nondementia group (P<0.05); the bilateral hippocampal volumes were a little smaller than those in nondementia group, but without statistical significance (P>0.05). Conclusion: The number, location and size of infarct, the degree of leukoaraiosis and brain atrophy have a close relation with the pathogenesis of subcortical ischemic vascular dementia.",adult;aged;article;brain atrophy;brain cortex;brain infarction;brain infarction size;brain ischemia;capsula interna;caudate nucleus;clinical article;cognitive defect;controlled study;correlation analysis;female;frontal cortex;hippocampus;human;image analysis;incidence;lateral brain ventricle;male;multiinfarct dementia;nuclear magnetic resonance imaging;pathogenesis;statistical significance;temporal cortex;thalamus;white matter,"Bai, Z. L.;Shi, X. Z.;Li, M.;Luo, J.",2007,,,0,
5515,Distinctive RNA expression profiles in blood associated with Alzheimer disease after accounting for white matter hyperintensities,"BACKGROUND: Defining the RNA transcriptome in Alzheimer Disease (AD) will help understand the disease mechanisms and provide biomarkers. Though the AD blood transcriptome has been studied, effects of white matter hyperintensities (WMH) were not considered. This study investigated the AD blood transcriptome and accounted for WMH. METHODS: RNA from whole blood was processed on whole-genome microarrays. RESULTS: A total of 293 probe sets were differentially expressed in AD versus controls, 5 of which were significant for WMH status. The 288 AD-specific probe sets classified subjects with 87.5% sensitivity and 90.5% specificity. They represented 188 genes of which 29 have been reported in prior AD blood and 89 in AD brain studies. Regulated blood genes included MMP9, MME (Neprilysin), TGFbeta1, CA4, OCLN, ATM, TGM3, IGFR2, NOV, RNF213, BMX, LRRN1, CAMK2G, INSR, CTSD, SORCS1, SORL1, and TANC2. CONCLUSIONS: RNA expression is altered in AD blood irrespective of WMH status. Some genes are shared with AD brain.",Aged;Alzheimer Disease/*blood/*genetics/pathology;Biomarkers/*blood;Female;Humans;Magnetic Resonance Imaging;Male;Oligonucleotide Array Sequence Analysis;RNA/*blood;Transcriptome;White Matter/*pathology,"Bai, Z.;Stamova, B.;Xu, H.;Ander, B. P.;Wang, J.;Jickling, G. C.;Zhan, X.;Liu, D.;Han, G.;Jin, L. W.;DeCarli, C.;Lei, H.;Sharp, F. R.",2014,Jul-Sep,10.1097/wad.0000000000000022,0,
5516,Abnormal white matter independent of hippocampal atrophy in amnestic type mild cognitive impairment,"Hippocampal atrophy is the key marker in the pathogenesis of Alzheimer's disease (AD), which is associated with white matter (WM) disruption. This type of WM disruption could partly explain AD-related pathology. However, relatively little attention has been directed toward WM disruption which may be independent of these fundamental gray matter (GM) changes in amnestic mild cognitive impairment (aMCI) which is associated with high risk of AD. To evaluate the differences of WM integrity between aMCI patients (N=32) and healthy controls (N=31), whole-brain voxel-based methods were applied to diffusion tensor imaging. To explore the possible independence of WM changes from GM loss, an index of hippocampal atrophy was used to partial out GM effects. aMCI patients showed WM disruption in frontal lobe, temporal lobe, internal capsule, cingulate gyrus and precuneus. The findings supported the evidence of independent patterns of degeneration in WM tracts which may co-act in the WM pathological process of aMCI patients. As aMCI is a putatively prodromal syndrome to AD, these data may assist with a better understanding of WM pathological change associated with the development of AD.","Aged;Aged, 80 and over;Atrophy;Cognition Disorders/ pathology;Diffusion Magnetic Resonance Imaging;Hippocampus/ pathology;Humans;Middle Aged","Bai, F.;Zhang, Z.;Watson, D. R.;Yu, H.;Shi, Y.;Yuan, Y.",2009,Sep 22,10.1016/j.neulet.2009.07.009,0,
5517,Topologically convergent and divergent structural connectivity patterns between patients with remitted geriatric depression and amnestic mild cognitive impairment,"Alzheimer's disease (AD) can be conceptualized as a disconnection syndrome. Both remitted geriatric depression (RGD) and amnestic mild cognitive impairment (aMCI) are associated with a high risk for developing AD. However, little is known about the similarities and differences in the topological patterns of white matter (WM) structural networks between RGD and aMCI. In this study, diffusion tensor imaging and deterministic tractography were used to map the human WM networks of 35 RGD patients, 38 aMCI patients, and 30 healthy subjects. Furthermore, graph theoretical methods were applied to investigate the alterations in the global and regional properties of the WM network in these patients. First, both the RGD and aMCI patients showed abnormal global topology in their WM networks (i.e., reduced network strength, reduced global efficiency, and increased absolute path length) compared with the controls, and there were no significant differences in these global network properties between the patient groups. Second, similar deficits of the regional and connectivity characteristics in the WM networks were primarily found in the frontal brain regions of RGD and aMCI patients compared with the controls, while a different nodal efficiency of the posterior cingulate cortex and several prefrontal brain regions were also observed between the patient groups. Together, our study provides direct evidence for the association of a great majority of convergent and a minority of divergent connectivity of WM structural networks between RGD and aMCI patients, which may lead to increasing attention in defining a population at risk of AD.","Aged;Anisotropy;Brain/metabolism/ pathology;Brain Mapping;Depression/ pathology;Diffusion Tensor Imaging;Female;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Mild Cognitive Impairment/ pathology;Neural Pathways/pathology;Neuropsychological Tests;Psychiatric Status Rating Scales","Bai, F.;Shu, N.;Yuan, Y.;Shi, Y.;Yu, H.;Wu, D.;Wang, J.;Xia, M.;He, Y.;Zhang, Z.",2012,Mar 21,10.1523/jneurosci.5061-11.2012,0,
5518,Neglect performance in acute stroke is related to severity of white matter hyperintensities,"BACKGROUND: Leukoaraiosis and its progression have longitudinally been associated with cognitive decline and dementia. Its role in acute cognitive function and response to acute cerebral ischemia is less well understood. We evaluated whether the presence and extent of leukoaraiosis, or white matter hyperintensities (WMH), had an impact on performance on tests of hemispatial neglect in acute ischemic stroke patients. METHODS: A series of 206 acute ischemic right-hemispheric stroke patients at Johns Hopkins Hospital underwent brain MRI and cognitive assessment for hemispatial neglect within 5 days of symptom onset. Error rates on neglect tests were evaluated, as were dichotomized measures of neglect, including 'any', 'severe' or 'worst' neglect, based on Z scores of at least 2 on 1, 2 or 3 tests (respectively) within a neglect battery. Acute infarct volumes were measured on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery images were reviewed for WMH, using the Cardiovascular Health Study (CHS) rating scale (ranging from 0 to 9, with 9 being 'most extensive'). Linear regression was used to evaluate 'error rate on neglect test' as the dependent variable, as a measure of neglect severity, with 'WMH category' as the primary independent variable, including adjustment for age, sex, race and infarct volume (on DWI). Logistic regression was used to evaluate a binary definition of neglect (defined as above) relative to the same independent variable and covariates. RESULTS: Each 1-point increase in CHS leukoaraiosis category was associated with 1.20-fold increased odds (95% CI: 1.00-1.43) of having any neglect, 1.23-fold increased odds (95% CI: 1.02-1.49) of having severe neglect and 1.33-fold increased odds of having worst neglect (95% CI: 1.01-1.76) after adjusting for infarct volume, age, sex and race. Increasing age and infarct size were also important predictors of neglect severity, with a 2.36% higher error rate (95% CI: 0.75-3.97%) on the line cancellation test associated with each category increase in CHS score; similar results were found for each of the neglect tests. Line cancellation neglect scores were worse in individuals with both severe WMH and large infarcts (p interaction, unadjusted=0.03). CONCLUSIONS: More severe leukoaraiosis is associated with more hemispatial neglect after acute ischemic stroke, independent of infarct volume, age and sex. We found not only more frequent neglect but also more severe neglect, based on error rates on neglect tests, in individuals with increasing leukoaraiosis. This emphasizes the importance of preexisting brain microvascular disease in outcomes of stroke patients. Further studies of the possible mechanism behind this association are needed.","Acute Disease;Aged;Cerebral Infarction/ complications/pathology/psychology;Disease Progression;Dominance, Cerebral;Female;Humans;Leukoaraiosis/ complications/pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Perceptual Disorders/ etiology/pathology;Sensitivity and Specificity","Bahrainwala, Z. S.;Hillis, A. E.;Dearborn, J.;Gottesman, R. F.",2014,,10.1159/000357661,0,
5519,Relationship of clinical and cognitive variables with brain morphometric abnormalities in Alzheimer's disease: a voxel based morphometric study using 3-tesla MRI,"Alzheimer's disease (AD) is associated with widespread structural and functional brain alterations. The current study examined the gray matter (GM) voxel based morphometric (VBM) correlates of cognitive and clinical severity scores in patients with AD. The study included 34 patients with AD according to NINCDS/ADRDA AD criteria and 28 matched elderly controls. All subjects were clinically evaluated using Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI) and the Clinical Dementia Rating (CDR) scale. The structural Magnetic Resonance Imaging (MRI) data were acquired using a 3 Tesla MRI scanner and VBM analysis was performed using VBM5.1 toolbox. The patients with AD had significantly lower GM volume, white matter volume and total brain volume as compared to controls. The HMSE scores were positively correlated (p=0.009) and EASI (p=0.04) & CDR (p=0.0004) were negatively correlated with the total GM volumes in patients with AD. The VBM analysis revealed diffuse GM atrophy in patients with AD. Frontal& temporal GM volumes were positively correlated with the HMSE scores. Thus the results of the study replicate the previous observations of generalized GM atrophy, in an Indian sample with AD. The cognitive decline, clinical dementia severity and impairment in activities of daily living were correlated whole brain GM and WM volumes as well as with specific brain regional atrophy in AD. However further studies with larger samples & with more detailed cognitive evaluation are required for confirmation & validation of the relationship between regional morphometric abnormalities and cognitive deficits in AD.",,"Bagepally, B. S.;John, J. P.;Varghese, M.;Halahalli, H. N.;Kota, L.;Sivakumar, P. T.;Bharath, S.;Jain, S.",2013,,10.14336/ad.2013.0400235,0,
5520,Apolipoprotein E4 and brain white matter integrity in Alzheimer's disease: tract-based spatial statistics study under 3-Tesla MRI,"INTRODUCTION: Apolipoprotein E4 (ApoE epsilon4) polymorphism is a known genetic risk factor for Alzheimer's disease (AD). OBJECTIVES: To evaluate the role of ApoE epsilon4 on white matter structural integrity in AD. METHODS: Subjects were 32 patients with probable AD (ApoE epsilon4-positive: n = 15) and 18 matched controls (ApoE epsilon4-positive: n = 6). All subjects were right-handed, evaluated using standard scales and genotyped at the ApoE locus. Diffusion tensor imaging was performed with a 3-tesla MRI scanner and analyzed using the tract-based spatial statistics method. RESULTS: AD patients had significantly lower fractional anisotropy (FA) in bilateral temporoparietal, limbic and parahippocampal regions in comparison to healthy comparison subjects. ApoE epsilon4 carriers among both AD and healthy comparison subjects showed lower FA in limbic and medial temporal regions. CONCLUSIONS: There is a modest association between ApoE epsilon4 carrier status and reduction in white matter tract integrity at medial temporal and limbic regions in both healthy and AD subjects.","Aged;Alzheimer Disease/ genetics/ pathology;Anisotropy;Apolipoprotein E4/ genetics;Brain/ pathology;Case-Control Studies;Diffusion Tensor Imaging;Female;Genotype;Humans;Imaging, Three-Dimensional;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Psychiatric Status Rating Scales","Bagepally, B. S.;Halahalli, H. N.;John, J. P.;Kota, L.;Purushottam, M.;Mukherjee, O.;Sivakumar, P. T.;Bharath, S.;Jain, S.;Varghese, M.",2012,,10.1159/000334761,0,
5521,Anterior cingulum white matter is altered in tobacco smokers,"BACKGROUND AND OBJECTIVES: The anterior cingulate cortex (ACC) is hypothesized to be involved in decision making and emotion regulation. Previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. The present study evaluated cingulum white matter in cigarette smokers. METHODS: Diffusion tensor imaging (DTI) in adult tobacco smokers and healthy non-smoker controls (total N = 70) was performed in a 3T Siemens Trio MRI scanner. RESULTS: Analyses of DTI tractography of the cingulum in tobacco-smoking individuals and controls indicated that tobacco abusers have significantly reduced fractional anisotropy (FA) in the right cingulum. In addition, FA in the left cingulum white matter was negatively associated with the number of cigarettes smoked per day and the Fagerstrom test for nicotine dependence, a self-report measure of tobacco dependence severity. CONCLUSIONS: The white matter of the cingulum is altered in a non-symmetrical way in tobacco smokers. An inverse relationship between FA and reported number of cigarettes per day was observed. Previous studies have also noted altered neural connectivity in cigarette smokers using similar methods. Similar white matter differences in the cingulum have been observed in methamphetamine dependent individuals and patients with dementia, which suggests that the cingulum may be altered by mechanisms not specific to tobacco exposure. SCIENTIFIC SIGNIFICANCE: By better understanding the effects of tobacco abuse on the brain, we hope to gain insight into how drug dependence influences the neurological foundations of behavior. (Am J Addict 2016;25:210-214).",,"Baeza-Loya, S.;Velasquez, K. M.;Molfese, D. L.;Viswanath, H.;Curtis, K. N.;Thompson-Lake, D. G.;Baldwin, P. R.;Ellmore, T. M.;De La Garza, R., 2nd;Salas, R.",2016,Apr,10.1111/ajad.12362,0,
5522,Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients,"BACKGROUND: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukaemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration. METHODS: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded. RESULTS: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion weighted imaging (DWI) of all patients revealed well demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum, corresponding to areas of decreased proton diffusion on apparent diffusion coefficient (ADC) maps (available in 21/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalisation of ADC abnormalities. However, fluid attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities. CONCLUSIONS: Several pathophysiological models of delayed leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic oedema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome.","Adult;Aged;Antineoplastic Agents/therapeutic use/ toxicity;Brain/ drug effects/pathology;Brain Edema/chemically induced/diagnosis;Capecitabine;Dementia, Vascular/ chemically induced/ diagnosis;Deoxycytidine/ analogs & derivatives/therapeutic use/toxicity;Diffusion Magnetic Resonance Imaging;Energy Metabolism/drug effects;Female;Fluorouracil/ analogs & derivatives/therapeutic use/ toxicity;Follow-Up Studies;Humans;Image Processing, Computer-Assisted;Infusions, Intravenous;Injections, Spinal;Magnetic Resonance Imaging;Male;Methotrexate/therapeutic use/ toxicity;Middle Aged;Neoplasms/drug therapy;Nerve Fibers, Myelinated/drug effects/pathology;Neurologic Examination/drug effects;Registries;Remission, Spontaneous;Stroke/ chemically induced/diagnosis;Tegafur/therapeutic use/ toxicity","Baehring, J. M.;Fulbright, R. K.",2008,May,10.1136/jnnp.2007.123737,0,
5523,Increased white matter hyperintensities in male methamphetamine abusers,"BACKGROUND: The current study was conducted to compare the prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance (MR) imaging in methamphetamine (MA) abusers. METHODS: Thirty-three MA abusers and 32 age- and gender-matched healthy comparison subjects were studied. Axial T-2 weighted images and fluid attenuated inversion recovery axial images were obtained using 3.0 T MR scanner. The severity of WMH was assessed separately for deep and periventricular WMH. Ordinal logistic regression models were used to assess the odds ratio for WMH. RESULTS: MA abusers had greater severity of WMH than the healthy comparison subjects (odds ratio: 7.06, 8.46, and 4.56 for all, deep, and periventricular WMH, respectively). Severity of deep WMH correlated with total cumulative dose of MA (p = 0.027). Male MA abusers had greater severity of WMH than female MA abusers (odds ratio = 10.00). While male MA abusers had greater severity of WMH than male comparison subjects (odds ratio = 18.86), there was no significant difference in WMH severity between female MA abusers and female comparison subjects. CONCLUSIONS: The current study reports increased WMH in MA abusers, which may be related to MA-induced cerebral perfusion deficits. In addition, female MA abusers had less severe WMH than male MA abusers, possibly due to estrogen's protective effect against ischemic or neurotoxic effects of MA.","Adult;Amphetamine-Related Disorders/ pathology;Brain/pathology;Cerebral Ventricles/pathology;Dementia, Vascular/ chemically induced/pathology;Demyelinating Diseases/ chemically induced/pathology;Dose-Response Relationship, Drug;Humans;Korea;Magnetic Resonance Imaging;Male;Methamphetamine/ toxicity;Midline Thalamic Nuclei/pathology;Neurotoxicity Syndromes/ pathology;Reference Values;Risk Factors;Statistics as Topic","Bae, S. C.;Lyoo, I. K.;Sung, Y. H.;Yoo, J.;Chung, A.;Yoon, S. J.;Kim, D. J.;Hwang, J.;Kim, S. J.;Renshaw, P. F.",2006,Jan 4,10.1016/j.drugalcdep.2005.05.016,0,
5524,Dissociation of Structural and Functional Integrities of the Motor System in Amyotrophic Lateral Sclerosis and Behavioral-Variant Frontotemporal Dementia,"BACKGROUND AND PURPOSE: This study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant fronto-temporal dementia (bvFTD; n=17) relative to healthy controls (n=37). METHODS: Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and diffusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. RESULTS: The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was affected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely affected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. CONCLUSIONS: Cross-correlation of structural and functional data further revealed a neural dissociation of different motor-system regions and tracts covarying with the TMS excitability across both patient groups. The structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.",,"Bae, J. S.;Ferguson, M.;Tan, R.;Mioshi, E.;Simon, N.;Burrell, J.;Vucic, S.;Hodges, J. R.;Kiernan, M. C.;Hornberger, M.",2016,Apr,10.3988/jcn.2016.12.2.209,0,
5525,The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease,"Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination-through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy.","0 (Biomarkers);Alzheimer Disease/diagnostic imaging/ pathology;Animals;Atrophy/pathology;Biomarkers;Diffusion Tensor Imaging/ methods;Disease Models, Animal;Fornix, Brain/diagnostic imaging/ pathology;Hippocampus/diagnostic imaging/ pathology;Mice;Mice, Transgenic;Microscopy, Electron/ methods;White Matter/diagnostic imaging/ pathology;Alzheimer's disease;Diffusion tensor imaging;Electron microscopy;Fornix;Mouse models","Badea, A.;Kane, L.;Anderson, R. J.;Qi, Y.;Foster, M.;Cofer, G. P.;Medvitz, N.;Buckley, A. F.;Badea, A. K.;Wetsel, W. C.;Colton, C. A.",2016,Nov 15,,0,5526
5526,The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease,"Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline. In vivo and ex vivo magnetic resonance imaging (MRI) revealed that CVN-AD mice replicate the hippocampal atrophy (6%), characteristic of humans with AD, and also present changes in subcortical areas. The largest effect was in the fornix (23% smaller), which connects the septum, hippocampus, and hypothalamus. In characterizing the fornix with diffusion tensor imaging, fractional anisotropy was most sensitive (20% reduction), followed by radial (15%) and axial diffusivity (2%), in detecting pathological changes. These findings were strengthened by optical microscopy and ultrastructural analyses. Ultrastructual analysis provided estimates of axonal density, diameters, and myelination-through the g-ratio, defined as the ratio between the axonal diameter, and the diameter of the axon plus the myelin sheath. The fornix had reduced axonal density (47% fewer), axonal degeneration (13% larger axons), and abnormal myelination (1.5% smaller g-ratios). CD68 staining showed that white matter pathology could be secondary to neuronal degeneration, or due to direct microglial attack. In conclusion, these findings strengthen the hypothesis that the fornix plays a role in AD, and can be used as a disease biomarker and as a target for therapy.",Alzheimer's disease;Diffusion tensor imaging;Electron microscopy;Fornix;Mouse models,"Badea, A.;Kane, L.;Anderson, R. J.;Qi, Y.;Foster, M.;Cofer, G. P.;Medvitz, N.;Buckley, A. F.;Badea, A. K.;Wetsel, W. C.;Colton, C. A.",2016,Aug 10,10.1016/j.neuroimage.2016.08.014,0,
5527,The generalizability of training gains in dementia: effects of an imagery-based mnemonic on face-name retention duration,"The generalizability of the results from a case study on the effects of an imagery mnemonic on face-name recall in dementia was examined (Hill, Evankovich, Sheikh, & Yesavage, 1987). Seven patients with Alzheimer's disease (AD) and 1 patient with multi-infarct dementia (MID) were trained by using the method devised by Hill et al. Application of the mnemonic increased the time during which face-name associations could be held in memory for 1 AD patient, and this improvement was maintained in a 1-month follow-up assessment. However, no training gains were observed for the remaining 7 patients, thus questioning the generalizability of this method in enhancing memory in dementia.","Aged;Alzheimer Disease/ psychology;Dementia, Multi-Infarct/ psychology;Face;Female;Form Perception;Generalization (Psychology);Humans;Imagination;Male;Mental Recall;Names;Neuropsychological Tests;Paired-Associate Learning;Retention (Psychology);Verbal Learning","Backman, L.;Josephsson, S.;Herlitz, A.;Stigsdotter, A.;Viitanen, M.",1991,Sep,,0,
5528,White matter lesions defined by diffusion tensor imaging in older adults,"OBJECTIVE: The cellular and molecular mechanisms underlying magnetic resonance imaging-defined white matter (WM) changes associated with age-related cognitive decline remain poorly defined. We tested the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury. METHODS: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population-based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D( perpendicular) ) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation. RESULTS: Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D( perpendicular) . Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA. INTERPRETATION: DTI-defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA-rich regions.","Aged;Aged, 80 and over;Alzheimer Disease/complications/pathology;Autopsy;Axons/pathology;Brain/ pathology;Cell Lineage/physiology;Cerebrovascular Disorders/complications/pathology;Cohort Studies;Data Interpretation, Statistical;Diffusion Tensor Imaging/ methods;Female;Free Radicals;Humans;Hyaluronic Acid/metabolism;Image Processing, Computer-Assisted;Immunohistochemistry;Male;Myelin Sheath/metabolism;Nerve Fibers, Myelinated/pathology;Oligodendroglia/physiology;Oxidative Stress/physiology;Prefrontal Cortex/pathology","Back, S. A.;Kroenke, C. D.;Sherman, L. S.;Lawrence, G.;Gong, X.;Taber, E. N.;Sonnen, J. A.;Larson, E. B.;Montine, T. J.",2011,Sep,10.1002/ana.22484,0,
5529,The clinical significance of 'white-matter-lesions' in myotonic dystrophy,30 patients with myotonic dystrophy (MD) were examined in order to define functional correlates of MRI findings. Typical cerebral findings in MRI were symmetrical multifocal white matter lesions (WML) in 70% associated with moderate cerebral atrophy in 43% and severe atrophy in 27%. 62% of patients showed significant cognitive impairment with preferential involvement of visual perception and concentration. Psychiatric features were observed in 67% and 33% satisfied criteria for syndrome of subcortical dementia. A strong correlation between MRI findings (especially extent of WML) and duration of disease and mental impairment was demonstrated. MD constitutes progressive cerebral disorder and WML are directly related to mental disturbance.,adolescent;adult;article;clinical article;cognitive defect;demyelinating disease;female;human;male;myotonic dystrophy;nuclear magnetic resonance imaging,"Bachmann, G.;Damian, M. S.;Schilling, G.",1993,,,0,
5530,White-matter lesions along the cholinergic tracts are related to cortical sources of EEG rhythms in amnesic mild cognitive impairment,"Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white-matter tracts. Eyes-closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white-matter tracts were detected with fluid-attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi-automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch-; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch-, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects.",Acetylcholine/ metabolism;Aged;Alpha Rhythm;Amnesia/complications/ pathology;Analysis of Variance;Brain Mapping;Cerebral Cortex/injuries/pathology/physiopathology;Cognition Disorders/complications/ pathology;Female;Humans;Magnetic Resonance Imaging;Male;Neural Pathways/pathology;Neuropsychological Tests;Spectrum Analysis,"Babiloni, C.;Pievani, M.;Vecchio, F.;Geroldi, C.;Eusebi, F.;Fracassi, C.;Fletcher, E.;De Carli, C.;Boccardi, M.;Rossini, P. M.;Frisoni, G. B.",2009,May,10.1002/hbm.20612,0,
5531,Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study,"Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.","Aged;Alzheimer Disease/pathology/ physiopathology;Cerebral Cortex/pathology/ physiopathology;Electroencephalography;Female;Humans;Italy;Magnetic Resonance Imaging;Male;Mild Cognitive Impairment/pathology/physiopathology;Nerve Fibers, Myelinated/pathology/ physiology;Neuropsychological Tests","Babiloni, C.;Lizio, R.;Carducci, F.;Vecchio, F.;Redolfi, A.;Marino, S.;Tedeschi, G.;Montella, P.;Guizzaro, A.;Esposito, F.;Bozzao, A.;Giubilei, F.;Orzi, F.;Quattrocchi, C. C.;Soricelli, A.;Salvatore, E.;Baglieri, A.;Bramanti, P.;Cavedo, E.;Ferri, R.;Cosentino, F.;Ferrara, M.;Mundi, C.;Grilli, G.;Pugliese, S.;Gerardi, G.;Parisi, L.;Vernieri, F.;Triggiani, A. I.;Pedersen, J. T.;Hardemark, H. G.;Rossini, P. M.;Frisoni, G. B.",2011,,10.3233/jad-2011-101710,0,
5532,White matter vascular lesions are related to parietal-to-frontal coupling of EEG rhythms in mild cognitive impairment,"Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto-parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white-matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white-matter vascular load was quantified based on magnetic resonance images (0-30 visual rating scale). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Directionality of fronto-parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto-parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at theta, alpha1, alpha2, and beta1 in MCI V+ (high vascular load; N = 42; MMSE = 26) than in MCI V- group (low vascular load; N = 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions.","Aged;Alzheimer Disease/pathology/physiopathology;Amnesia/pathology/physiopathology;Arterioles/pathology;Biomarkers/analysis;Cerebral Arteries/pathology;Cerebrum/pathology/ physiopathology;Cognition Disorders/pathology/ physiopathology;Dementia, Vascular/pathology/ physiopathology;Disease Progression;Electroencephalography/ methods;Evoked Potentials/ physiology;Frontal Lobe/pathology/physiopathology;Humans;Magnetic Resonance Imaging/ methods;Models, Neurological;Nerve Fibers, Myelinated/pathology;Neural Pathways/pathology/physiopathology;Parietal Lobe/pathology/physiopathology;Predictive Value of Tests","Babiloni, C.;Frisoni, G. B.;Pievani, M.;Vecchio, F.;Infarinato, F.;Geroldi, C.;Salinari, S.;Ferri, R.;Fracassi, C.;Eusebi, F.;Rossini, P. M.",2008,Dec,10.1002/hbm.20467,0,
5533,White-matter vascular lesions correlate with alpha EEG sources in mild cognitive impairment,"It is an open issue if vascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI), as a preclinical stage of Alzheimer's disease (AD) at group level. In the present study, we tested the hypothesis that electroencephalographic (EEG) alpha rhythms, which are affected (i.e. decreased in amplitude) by AD processes, are relatively preserved in MCI subjects in whom the cognitive decline is mainly explained by white-matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold), 80 MCI, and 40 AD subjects. In the MCI subjects, white-matter vascular load was quantified based on MRI (0-30 Wahlund visual rating scale). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), and beta 2 (20-30Hz). Low resolution electromagnetic source tomography (LORETA) was used for EEG source analysis. As expected, we observed that alpha 1 sources in parietal, occipital, and temporal areas were lower in amplitude in the AD and MCI subjects than in the Nold subjects, whereas the amplitude of wide delta sources was higher in the AD than in the Nold and MCI subjects. As novel results, the amplitude of parietal, occipital, and temporal alpha 1 sources was higher in the MCI V+ (high vascular load; N=42; MMSE=26) than MCI V- group (low vascular load; N=37; MMSE=26.7). Furthermore, a weak but significant (p<0.05) positive statistical correlation was found between the parietal alpha 1 sources and the score of Wahlund scale across all MCI subjects (i.e. the more severe white-matter lesions, the higher parietal alpha source power). The present results are in line with the additive model of cognitive impairment postulating that this arises as the sum of neurodegenerative and cerebrovascular lesions.",Aged;*Alpha Rhythm;Alzheimer Disease/pathology/physiopathology;*Brain Mapping;Cerebral Cortex/*pathology/physiopathology;Cerebrovascular Disorders/etiology/*pathology;Cognition Disorders/*complications/*pathology;Female;Humans;Magnetic Resonance Imaging;Male;Mental Status Schedule;Neuropsychological Tests;Spectrum Analysis,"Babiloni, C.;Frisoni, G. B.;Pievani, M.;Toscano, L.;Del Percio, C.;Geroldi, C.;Eusebi, F.;Miniussi, C.;Rossini, P. M.",2008,,10.1016/j.neuropsychologia.2008.03.021,0,
5534,Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease,"Objective: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. Methods: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). Results: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. Conclusions: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. Significance: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD. © 2006 International Federation of Clinical Neurophysiology.",,"Babiloni, C.;Frisoni, G.;Steriade, M.;Bresciani, L.;Binetti, G.;Del Percio, C.;Geroldi, C.;Miniussi, C.;Nobili, F.;Rodriguez, G.;Zappasodi, F.;Carfagna, T.;P, M. R.",2006,May,,0,
5535,"Hereditary diffuse leukoencephalopathy with spheroids: Clinical, pathologic and genetic studies of a new kindred","Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with axonal spheroids leading to progressive cognitive and motor dysfunction. We report clinical and pathological features, as well as molecular genetic analysis, of a family with HDLS. A pedigree consisting of 27 persons in 5 generations contained 6 affected individuals. Dementia and depression were common; two individuals presented with a syndrome resembling corticobasal degeneration (CBD). Postmortem neuropathologic evaluation of three affected individuals revealed enlargement of the lateral ventricles and marked attenuation of cerebral white matter, but preservation of white matter in brainstem and cerebellum, except for the corticospinal tract. Histopathologic studies showed a loss of myelinated fibers, lipid-laden macrophages and bizarre astrocytes, as well as abundant axonal spheroids that were immunoreactive for phosphorylated neurofilament protein and amyloid precursor protein (APP), but not αB-crystallin and variably with ubiquitin. By electron microscopy, axonal spheroids contained aggregates of intermediate filaments or of organelles that were predominantly vesicular and lamellar. The cerebral cortex had focal neuronal degeneration with αB-crystallin-immunoreactive ballooned neurons. In summary, the present report describes a previously unreported kindred with HDLS with individuals presenting as CBD. Immunohistochemistry for APP and αB-crystallin demonstrates distinctive neurodegeneration in cerebral axons and perikarya. © Springer-Verlag 2006.",alpha crystallin;amyloid precursor protein;guanine nucleotide exchange factor;lipid;neurofilament protein;ubiquitin;adult;aged;Alzheimer disease;apraxia;article;astrocyte;autopsy;autosomal dominant disorder;brain ventricle dilatation;cell organelle;clinical article;clinical feature;computer assisted tomography;corticobasal degeneration;degenerative disease;dementia;demyelination;depression;differential diagnosis;electroencephalogram;electron microscopy;female;genetic analysis;hereditary diffuse leukoencephalopathy with spheroid;histopathology;human;human tissue;immunohistochemistry;immunoreactivity;intermediate filament;lateral brain ventricle;macrophage;male;memory disorder;molecular genetics;mutational analysis;nerve cell degeneration;neuropathology;nuclear magnetic resonance imaging;parkinsonism;pedigree;priority journal;protein phosphorylation;pyramidal sign;seizure;spheroid cell;white matter,"Baba, Y.;Ghetti, B.;Baker, M. C.;Uitti, R. J.;Hutton, M. L.;Yamaguchi, K.;Bird, T.;Lin, W.;DeLucia, M. W.;Dickson, D. W.;Wszolek, Z. K.",2006,,,0,
5536,[Postoperative cognitive dysfunction in off-pump versus on-pump coronary artery bypass surgery],"Patients referred for coronary artery bypass grafting (CABG) are older and more likely to have extensive vascular diseases than those referred for such procedures in the past. Undiagnosed cerebral small vessel diseases (SVD), such as lacunar infarctions or white matter lesions, and dementia are common. Postoperative cognitive dysfunction (POCD) remains a major concern in these elderly patients. POCD is caused by cerebral emboli, hypoperfusion, and inflammation attributed largely to the use of cardiopulmonary bypass. Off-pump CABG is a surgical strategy proposed to decrease the risk of POCD. Although some researchers have found that off-pump CABG is associated with improved cognitive outcome in the early postoperative period, many studies have shown no difference at any time points. Consequently, efforts to reduce the incidence of POCD are focusing on patient-related rather than procedure-related factors. Surgical procedures could exacerbate neuroinflammation and accelerate cognitive dysfunction, especially in patients with SVD and dementia. Mild cognitive impairment may serve as a surrogate marker for underlying SVD or dementia. Preoperative cerebrovascular evaluation, such as MRI, MRA, or cervical ultrasound, and cognitive screening may be effective to identify high-risk patients, making it possible to individualize surgical approaches aimed at reducing POCD.","Aged;Cognition Disorders/etiology/*physiopathology/prevention & control;Coronary Artery Bypass/*methods;Coronary Artery Bypass, Off-Pump/*methods;*Heart-Assist Devices;Humans;Randomized Controlled Trials as Topic","Baba, T.;Maekawa, K.;Otomo, S.;Tokunaga, Y.;Oyoshi, T.",2014,Nov,,0,
5537,Adult-onset genetic leukoencephalopathies: A MRI pattern-based approach in a comprehensive study of 154 patients,"Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.",,"Ayrignac, X.;Carra-Dalliere, C.;De Champfleur, N. M.;Denier, C.;Aubourg, P.;Bellesme, C.;Castelnovo, G.;Pelletier, J.;Audoin, B.;Kaphan, E.;De Seze, J.;Collongues, N.;Blanc, F.;Chanson, J. B.;Magnin, E.;Berger, E.;Vukusic, S.;Durand-Dubief, F.;Camdessanche, J. P.;Cohen, M.;Lebrun-Frenay, C.;Brassat, D.;Clanet, M.;Vermersch, P.;Zephir, H.;Outteryck, O.;Wiertlewski, S.;Laplaud, D. A.;Ouallet, J. C.;Brochet, B.;Goizet, C.;Debouverie, M.;Pittion, S.;Edan, G.;Deburghgraeve, V.;Le Page, E.;Verny, C.;Amati-Bonneau, P.;Bonneau, D.;Hannequin, D.;Guyant-Maréchal, L.;Derache, N.;Defer, G. L.;Moreau, T.;Giroud, M.;Guennoc, A. M.;Clavelou, P.;Taithe, F.;Mathis, S.;Neau, J. P.;Magy, L.;Devoize, J. L.;Bataillard, M.;Masliah-Planchon, J.;Dorboz, I.;Tournier-Lasserve, E.;Levade, T.;Tanguy, O. B.;Labauge, P.",2015,1,,0,
5538,Longitudinal change in regional brain volumes in prodromal Huntington disease,"OBJECTIVE: As therapeutics are being developed to target the underlying neuropathology of Huntington disease, interest is increasing in methodologies for conducting clinical trials in the prodromal phase. This study was designed to examine the potential utility of structural MRI measures as outcome measures for such trials. METHODS: Data are presented from 211 prodromal individuals and 60 controls, scanned both at baseline and at the 2-year follow-up. Prodromal participants were divided into groups based on proximity to estimated onset of diagnosable clinical disease: far (>15 years from estimated onset), mid (9-15 years) and near (<9 years). Volumetric measurements of caudate, putamen, total striatum, globus pallidus, thalamus, total grey and white matter and cerebrospinal fluid were performed. RESULTS: All prodromal groups showed a faster rate of atrophy than controls in striatum, total brain and cerebral white matter (especially in the frontal lobe). Neither prodromal participants nor controls showed any significant longitudinal change in cortex (either total cortical grey or within individual lobes). When normal age-related atrophy (ie, change observed in the control group) was taken into account, there was more statistically significant disease-related atrophy in white matter than in striatum. CONCLUSION: Measures of volume change in striatum and white-matter volume, particularly in the frontal lobe, may serve as excellent outcome measures for future clinical trials in prodromal Huntington disease. Clinical trials using white matter or striatal volume change as an outcome measure will be most efficient if the sample is restricted to individuals who are within 15 years of estimated onset of diagnosable disease.","Adult;Atrophy/pathology;Brain/*pathology;*Disease Progression;Female;Humans;Huntington Disease/diagnosis/*pathology;Longitudinal Studies;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Nerve Fibers, Unmyelinated/pathology;Time Factors","Aylward, E. H.;Nopoulos, P. C.;Ross, C. A.;Langbehn, D. R.;Pierson, R. K.;Mills, J. A.;Johnson, H. J.;Magnotta, V. A.;Juhl, A. R.;Paulsen, J. S.",2011,Apr,10.1136/jnnp.2010.208264,0,
5539,Striatal volume contributes to the prediction of onset of Huntington disease in incident cases,"BACKGROUND: Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset. METHODS: The current study examined magnetic resonance imaging (MRI) measures of striatum and white matter volume in 85 individuals prospectively followed from pre-HD stage through diagnosable motor onset (incident cases) and 85 individuals individually matched with incident cases on CAG repeat length, sex, and age, who were not diagnosed with HD during the course of the study. RESULTS: Volumes of striatum and white matter were significantly smaller in individuals who would be diagnosed 1 to 4 years following the initial MRI scan, compared with those who would remain in the pre-HD stage. Putamen volume was the measure that best distinguished between the two groups. CONCLUSIONS: Results suggest that MRI volumetric measures may be helpful in selecting individuals for future clinical trials in pre-HD where HD motor onset is the primary outcome measure. In planning for multisite clinical trials in pre-HD, investigators may also want to consider using more objective measures, such as MRI volumes, in addition to onset of diagnosable movement disorder, as major outcome measures.","Adult;Atrophy/pathology;Case-Control Studies;Corpus Striatum/ pathology;Disease Progression;Female;Humans;Huntington Disease/diagnosis/genetics/ pathology;Magnetic Resonance Imaging/methods;Male;Middle Aged;Nerve Fibers, Unmyelinated/pathology;Neuroimaging/methods;Predictive Value of Tests;Trinucleotide Repeats","Aylward, E. H.;Liu, D.;Nopoulos, P. C.;Ross, C. A.;Pierson, R. K.;Mills, J. A.;Long, J. D.;Paulsen, J. S.",2012,May 1,10.1016/j.biopsych.2011.07.030,0,
5540,Regional atrophy associated with cognitive and motor function in prodromal Huntington disease,"Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis (""pre-HD""). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.",adult;article;atrophy;brain;cognition;cognitive;cognitive defect;computer assisted diagnosis;female;human;Huntington chorea;male;motor;multicenter study;neuropsychological test;nuclear magnetic resonance imaging;pathology;prodromal symptom;psychiatric;psychomotor performance,"Aylward, E. H.;Harrington, D. L.;Mills, J. A.;Nopoulos, P. C.;Ross, C. A.;Long, J. D.;Liu, D.;Westervelt, H. K.;Paulsen, J. S.;Investigators, Predict-Hd;Coordinators of the Huntington Study, Group",2013,,,0,
5541,Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia,"Objective: The authors recently reported smaller basal ganglia volumes for patients with HIV-associated dementia than for HIV-infected patients without dementia and a seronegative comparison group. The purpose of the current study was to determine whether HIV dementia is associated with volume reductions in other brain regions. Method: The authors measured volumes of CSF and gray and white tissue on cranial magnetic resonance images from homosexual men who were 1) infected with HIV with HIV-associated dementia complex, 2) infected with HIV without dementia, and 3) HIV seronegative. Results: Results suggest that loss of white matter occurs with HIV infection and is more severe in HIV-positive patients with dementia than in those without dementia. There was some generalized volume reduction in gray matter in HIV-positive demented patients, although group differences did not reach significance when adjusted for age. Volume of posterior cortex, however, was significantly smaller among HIV-positive patients with dementia than in either remaining group. There were no significant differences between HIV- positive nondemented patients and HIV-negative subjects in these regions. Conclusions: In conjunction with findings from previous research, the authors conclude that HIV dementia is associated with specific gray matter volume reduction in basal ganglia and posterior cortex, as well as with generalized volume reduction of white matter.",,"Aylward, E. H.;Brettschneider, P. D.;McArthur, J. C.;Harris, G. J.;Schlaepfer, T. E.;Henderer, J. D.;Barta, P. E.;Tien, A. Y.;Pearlson, G. D.",1995,July,,0,
5542,Frontal lobe volume in patients with Huntington's disease,"Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntington's disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function. Patients who were mildly affected had frontal lobe volumes (both gray and white matter) essentially identical to those of control subjects, despite clearly abnormal basal ganglia. Patients who were moderately affected demonstrated significant reductions in total frontal lobe volume (17%) and frontal white matter volume (28%). Frontal lobe white matter volume reductions, but not total frontal lobe volume reductions, were disproportionately greater than overall brain volume reductions (17%). Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after taking into account total brain volume. We conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy, but this association is not specific to the frontal lobes. Frontal lobe atrophy (like total brain atrophy) occurs in later stages of increasing HD symptom severity and this atrophy primarily involves white matter.",Adult;Atrophy;Cognition Disorders/pathology;Female;Frontal Lobe/*pathology;Humans;Huntington Disease/diagnosis/*pathology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests,"Aylward, E. H.;Anderson, N. B.;Bylsma, F. W.;Wagster, M. V.;Barta, P. E.;Sherr, M.;Feeney, J.;Davis, A.;Rosenblatt, A.;Pearlson, G. D.;Ross, C. A.",1998,Jan,,0,
5543,Imaging cerebral microbleeds using susceptibility weighted imaging: one step toward detecting vascular dementia,"PURPOSE: To monitor changes in the number of cerebral microbleeds (CMBs) in a longitudinal study of healthy controls (HC) and mild-cognitively impaired (MCI) patients using susceptibility weighted imaging (SWI). MATERIALS AND METHODS: SWI was used to image 28 HC and 75 MCI patients annually at 1.5 Tesla over a 4-year period. Magnitude and phase data were used to visualize CMBs for the first and last scans of 103 subjects. RESULTS: Preliminary analysis revealed that none of the 28 HC had more than three CMBs. In the 75 MCI patients, five subjects had more than three CMBs in both first and last scans, while one subject had more than three bleeds only in the last scan. In five of these six MCI patients, the number of CMBs increased over time and all six went on to develop progressive cognitive impairment (PCI). Of the 130 total CMBs seen in the last scans of the six MCI cases, most were less than 4 mm in diameter. CONCLUSION: SWI can reveal small CMBs on the order of 1 mm in diameter and this technique can be used to follow their development longitudinally. Monitoring CMBs may be a means by which to evaluate patients for the presence of microvascular disease that leads to PCI.","Aged;Aged, 80 and over;Cerebral Hemorrhage/complications/ diagnosis;Cognition Disorders/complications/ diagnosis;Dementia, Vascular/complications/ diagnosis;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Angiography/ methods;Male;Middle Aged;Reproducibility of Results;Sensitivity and Specificity","Ayaz, M.;Boikov, A. S.;Haacke, E. M.;Kido, D. K.;Kirsch, W. M.",2010,Jan,10.1002/jmri.22001,0,
5544,Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus,"We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis. © 2008 Springer Medizin Verlag.",,"Axer, H.;Hüge, S.;Wilhelm, C.;Axer, M.;Kunze, A.;Reichenbach, J. R.;Freesmeyer, M.;Kohlhase, J.;Sauer, H.;Bär, K. J.",2009,January,,0,
5545,MRI demonstration and GT correlation of the brain in patients with idiopathic intracerebral calcification,"Twenty-two patients aged 36-63 years were diagnosed as having Fahr's syndrome on the basis of the presence on CT of unexpected extensive calcification of the basal ganglia. Even when associated with calcification of other brain areas, the main diagnostic criterion remained basal ganglia calcification larger than 800 mm(2). Normal values of parathormone, serum calcium and phosphorus excluded hypercalcaemia and hypoparathyroidism. Mitochondrial CNS disease was excluded clinically. MRI and repeated CT and neurological examination were performed in all of the patients. The patients were divided into two groups: neurologically asymptomatic (group 1) and neurologically symptomatic (group 2). T2-weighted sequences demonstrated hyperintense areas in all of the patients involving the white and the grey matter of the brain. In group 1 the hyperintense lesions were significantly smaller than in group 2. The neurological symptoms correlated better with the hyperintensities on T2-weighted MR images than with the calcification demonstrated on CT. Hyperintensities in T2-weighted MRI and the areas shown by CT to have calcification had different locations. In 15 patients with dementia, the white matter of the entire centrum semiovale was bilaterally hyperintense. In another 3 patients with hemiparesis, hyperintense areas in the internal capsule, contralateral to the side of hemiparesis, were demonstrated in the T2-weighted sequence. The hyperintense T2 signals may reflect a slowly progressive, metabolic or inflammatory process in the brain which subsequently calcifies and are probably responsible for the neurological deficit observed.",,"Avrabami, E.;Cohn, D. F.;Feibel, M.;Tadmor, R.",1994,1994,,0,
5546,Cerebral autoregulation and brain networks in occlusive processes of the internal carotid artery,"Patients with unilateral occlusive processes of the internal carotid artery (ICA) show subtle cognitive deficits. Decline in cerebral autoregulation and in functional and structural integrity of brain networks have previously been reported in the affected hemisphere (AH). However, the association between cerebral autoregulation, brain networks, and cognition remains to be elucidated. Fourteen neurologically asymptomatic patients (65±11 years) with either ICA occlusion or high-grade ICA stenosis and 11 age-matched healthy controls (HC) (67±6 years) received neuropsychologic testing, transcranial Doppler sonography to assess cerebral autoregulation using vasomotor reactivity (VMR), and magnetic resonance imaging to probe white matter microstructure and resting-state functional connectivity (RSFC). Patients performed worse on memory and executive tasks when compared with controls. Vasomotor reactivity, white matter microstructure, and RSFC were lower in the AH of the patients when compared with the unaffected hemisphere and with controls. Lower VMR of the AH was associated with several ipsilateral clusters of lower white matter microstructure and lower bilateral RSFC in patients. No correlations were found between VMR and cognitive scores. In sum, impaired cerebral autoregulation was associated with reduced structural and functional connectivity in cerebral networks, indicating possible mechanisms by which severe unilateral occlusive processes of the ICA lead to cognitive decline.",,"Avirame, K.;Lesemann, A.;List, J.;Witte, A. V.;Schreiber, S. J.;Flöel, A.",2015,2,,0,
5547,A new Spanish family with CADASIL associated with 346C>T mutation of NOTCH3 gene,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited condition characterized by migraine, recurrent strokes, and subcortical dementia. Other manifestations as psychiatric disturbances, seizures, hypoacusia or learning disorders have been reported. CADASIL may be suspected based on clinical syndrome, a positive family history, and a typical cranial magnetic resonance image with T2/FLAIR hyperintense signals in the temporopolar white matter or the external capsule. Bilateral white matter abnormalities are invariably seen and often small subcortical infarcts are also present. Accumulation of the granular osmiophilic material on skin biopsy may help in diagnosis. Mutations in the NOTCH3 gene localized in chromosome 19 are involved in its pathogenesis. Only 11 families from Spain have been reported. Here we describe two members of a family with clinical symptoms and neuroimaging of CADASIL. The skin biopsy was negative. In both patients 346C>T mutation in exon 3 of NOTCH3 gene was found. There is the first Spanish family reported with CADASIL, caused by the 346C>T mutation in NOTCH3 gene which was frequently described in the European series.",,"Ávila, A.;Bello, J.;Maho, P.;Gómez, M. I.",2007,September,,0,
5548,Clinical and neurovisualization characteristics of apathetic depression,"Objective. To study apathetic depression first diagnosed at late age and identify its relation to cognitive and social dysfunction as well as to morphological and functional changes in the brain. Material and methods. Thirty-two patients at the age above 60 years with newly diagnosed depressive episode and 15 healthy age-matched volunteers were included in the study. All patients were divided into two groups by the score on the Apathy scale (AS): >14 — depression with apathy (n=21), <14 — depression without apathy (n=11). Patients were examined using psychometric methods (HAMD, GDS, AS, SHAPS, SF-36, MoCA-test), neuroimaging (MRI scanner with a magnetic field strength of 1.5 Tesla — EXCEL ART Vantage Atlas-X, Toshiba, Japan) and statistical data analysis. Results and conclusion. Apathy component in clinical depression reflects a tendency towards the increase in depression severity and cognitive deterioration that results in the substantial lowering of quality of life and correlates with cerebrovascular changes, decrease in gray and white matter volume and mean cortical thickness of large hemispheres.",EXCEL ART Vantage Atlas-X;adult;aged;apathy;Apathy scale;article;brain cortex;brain function;clinical article;clinical feature;cognition;controlled study;cortical thickness (brain);disease severity;Geriatric Depression Scale;gray matter;Hamilton Depression Rating Scale;human;major depression;mental deterioration;mental disease assessment;middle aged;Montreal cognitive assessment;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;psychometry;quality of life;scoring system;Short Form 36;Snaith Hamilton Pleasure Scale;social disability;white matter,"Avedisova, A. S.;Zakharova, K. V.;Gaskin, V. V.;Samotaeva, I. S.;Arkusha, I. A.",2017,,10.17116/jnevro20171178111-17,0,
5549,Dementia induces correlated reductions in white matter integrity and cortical thickness: a multivariate neuroimaging study with sparse canonical correlation analysis,"We use a new, unsupervised multivariate imaging and analysis strategy to identify related patterns of reduced white matter integrity, measured with the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI), and decreases in cortical thickness, measured by high resolution T1-weighted imaging, in Alzheimer's disease (AD) and frontotemporal dementia (FTD). This process is based on a novel computational model derived from sparse canonical correlation analysis (SCCA) that allows us to automatically identify mutually predictive, distributed neuroanatomical regions from different imaging modalities. We apply the SCCA model to a dataset that includes 23 control subjects that are demographically matched to 49 subjects with autopsy or CSF-biomarker-diagnosed AD (n=24) and FTD (n=25) with both DTI and T1-weighted structural imaging. SCCA shows that the FTD-related frontal and temporal degeneration pattern is correlated across modalities with permutation corrected p<0.0005. In AD, we find significant association between cortical thinning and reduction in white matter integrity within a distributed parietal and temporal network (p<0.0005). Furthermore, we show that-within SCCA identified regions-significant differences exist between FTD and AD cortical-connective degeneration patterns. We validate these distinct, multimodal imaging patterns by showing unique relationships with cognitive measures in AD and FTD. We conclude that SCCA is a potentially valuable approach in image analysis that can be applied productively to distinguishing between neurodegenerative conditions.","Alzheimer Disease/cerebrospinal fluid/ pathology;Anisotropy;Biomarkers/cerebrospinal fluid;Brain/ pathology;Cerebral Cortex/pathology;Computer Simulation;Databases, Factual;Dementia/cerebrospinal fluid/pathology;Diffusion Tensor Imaging/methods;Female;Frontotemporal Dementia/cerebrospinal fluid/ pathology;Humans;Image Processing, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Models, Neurological;Multivariate Analysis;Nerve Fibers, Myelinated/pathology;Organ Size","Avants, B. B.;Cook, P. A.;Ungar, L.;Gee, J. C.;Grossman, M.",2010,Apr 15,10.1016/j.neuroimage.2010.01.041,0,
5550,Sparse unbiased analysis of anatomical variance in longitudinal imaging,"We present a new algorithm for reliable, unbiased, multivariate longitudinal analysis of cortical and white matter atrophy rates with penalized statistical methods. The pipeline uses a step-wise approach to transform and personalize template information first to a single-subject template (SST) and then to the individual's time series data. The first stream of information flows from group template to the SST; the second flows from the SST to the individual time-points and provides unbiased, prior-based segmentation and measurement of cortical thickness. MRI-bias correction, consistent longitudinal segmentation, cortical parcellation and cortical thickness estimation are all based on strong use of the subject-specific priors built from initial diffeomorphic mapping between the SST and optimal group template. We evaluate our approach with both test-retest data and with application to a driving biological problem. We use test-retest data to show that this approach produces (a) zero change when the retest data contains the same image content as the test data and (b) produces normally distributed, low variance estimates of thickness change centered at zero when test-retest data is collected near in time to test data. We also show that our approach--when combined with sparse canonical correlation analysis--reveals plausible, significant, annualized decline in cortical thickness and white matter volume when contrasting frontotemporal dementia and normal aging.","Algorithms;Analysis of Variance;Brain/ pathology;Brain Diseases/ pathology;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Pattern Recognition, Automated/ methods;Prognosis;Reproducibility of Results;Sensitivity and Specificity;Subtraction Technique","Avants, B.;Cook, P. A.;McMillan, C.;Grossman, M.;Tustison, N. J.;Zheng, Y.;Gee, J. C.",2010,,,0,
5551,Gait analysis under dual-task conditions for identifying motor phenotypes in elderly patients with gait disorders,"OBJECTIVE: Gait disorders are associated with increased fall risk, dementia and loss of autonomy. Gait analysis has previously been validated in the identification of motor phenotypes in mild cognitive impairment [1]. We hypothesized that gait analysis under dual-task conditions in elderly patients with gait disorders might allow the identification of motor phenotypes linked to specific brain abnormalities. MATERIAL/PATIENTS AND METHODS: An observational study was instructed for elderly patients with gait disorders or memory impairment. Gait analysis under dual-task conditions was carried out for all patients (Locometrix(R)). Two main gait variables were measured: stride frequency, and stride regularity. For each gait variable, the dual task cost, which is related to cognitive reserve (DTC (%)) was calculated as follows: [DTC %=(single-task gait value-dual task gait value)/single-task gait valuex100]. Brain MRI was carried out in the absence of contra-indications. Semi-quantitative score for white matter hyper intensities (age-related white matter changes, ARWMC) and hippocampus atrophy (Scheltens) were identified. RESULTS: One hundred and three patients (mean age 76.3+/-7.2, women 56%) were included. Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The quartile analysis of DTC for stride frequency and stride regularity allowed the identification of 3 motor phenotypes (<0.01KW), with no link to either sex or clinical subgroups, but characterized by different Scheltens scores (P=0.05). Twenty-six patients with a low value of DTC for stride frequency and a high value of DTC for Stride Regularity (Scheltens 2.6+/-1.6). Forty-seven patients with the same value of DTC for both stride frequency and regularity (Scheltens 3.3+/-1.6). 30 patients with a high value of DTC for stride frequency and a low value of DTC for stride regularity (Scheltens 4.0+/-1.9). DISCUSSION-CONCLUSION: The identification of different motor phenotypes in elderly patients with gait disorders can help the clinician with diagnoses and tailored cognitivo-motor gait rehabilitation.",Dual task paradigm;Elderly;Gait analysis;Gait disorders;Motor phenotypes,"Auvinet, B.;Touzard, C.;Goeb, V.",2016,Sep,,0,
5552,JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence,"Juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3) is an inherited lysosomal disease. We used longitudinal MRI, for the first time, to evaluate the rate of brain volume alterations in JNCL. Six patients (mean ages of 12.4 years and 17.3 years) and 12 healthy controls were studied twice with 1.5 T MRI. White matter (WM), gray matter (GM) and CSF volumes were measured from the sets of T1-weighted 3-dimensional MR images using a fully automated image-processing procedure. The brain volume alterations were calculated as percentage change per year. The GM and whole brain volumes decreased and the CSF volume increased significantly more in the patients than in controls (p-values for the null hypothesis of equal means were 0.001, 0.004, and 0.005, respectively). We found no difference in the WM volume change between the populations. In patients, the GM volume decreased 2.4 % (SD 0.5 %, p 0.0001 for the null hypothesis of zero mean change between observations), the whole brain volume decreased 1.1 % (SD 0.5 %, p = 0.003), and the CSF volume increased 2.7 % (SD 1.8 %, p = 0.01) per year. In normal controls, only the mean white matter volume was significantly altered (0.8 % increase",,"Autti, T. H.;Hämäläinen, J.;Mannerkoski, M.;Van Leemput, K.;Åberg, L. E.",2008,August,,0,
5553,MRI of neuronal ceroid lipofuscinosis: I. Cranial MRI of 30 patients with juvenile neuronal ceroid lipofuscinosis,"We studied 30 patients with juvenile neuronal ceroid lipofuscinosis (JNCL). The patients (aged 6-25 years) and 43 age-matched healthy volunteers underwent MRI. After visual assessment, the signal intensity was measured on T2-weighted images in numerous locations. The thickness of the cortex and corpus callosum and the dimensions of the brain stem were measured. Mild to moderate cerebral atrophy was found in 14 of 30 patients, most of them over 14 years of age; 5 older patients had mild to moderate cerebellar atrophy. There was reduction in the size of the corpus callosum and brain stem. The thalamus, caudate nucleus and putamen appeared to give low signal in patients from the ages of 7, 11 and 11 years, respectively. In contrast, the signal intensity measured from the thalamus in these patients showed only a slight (insignificant) decrease compared with controls. The most significant alteration, an increase in measured signal intensity, was found in the white matter (P < 0.0001), even in the youngest patients. The MRI findings correlated significantly with decreased intelligence, speech disturbances and motor problems. Although MRI findings in JNCL do not appear very specific and the visual changes develop relatively late, the absence of pathological MRI findings in the very early stage of the disease may play a part in differential diagnosis of the different types of NCL. Furthermore, the MRI findings may be used in assessing severity and prognosis, particularly in young patients.",,"Autti, T.;Raininko, R.;Vanhanen, S. L.;Santavuori, P.",1996,July,,0,
5554,MRI of neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile or late infantile type,"Postmortem MRI was carried out on the formalin-fixed brains of 14 patients with juvenile (JNCL) and two with late infantile neuronal ceroid lipofuscinosis, one of variant and the other of classical type. Two patients with JNCL had also undergone MRI during life. After MRI, specimens for histopathological analysis were taken from standard areas of the cerebral cortex, deep nuclei and white matter. The signal intensity of the periventricular white matter was usually higher than that of the peripheral white matter, a finding which correlated with the severe periventricular loss of myelin and gliosis observed histologically. The signal intensity was usually lower in the thalamus than in the putamen; in some patients the signal intensity of the thalamus was equal to or even lower than that of the white matter. However, myelin loss, gliosis, the storage process or neuronal loss in the thalamus did not correlate with the MRI findings. Since in one patient with JNCL the ante- and postmortem MRI did not differ basically, it appears probable that the periventricular changes detected in vivo on MRI are due to the severe loss of myelin and gliosis observed in this study. However, changes resulting from the fixation process must be considered, when postmortem and in vivo MRI are correlated.",myelin;adolescent;adult;article;autopsy;brain cortex;brain nucleus;brain ventricle;clinical article;female;gliosis;histopathology;human;human tissue;male;neuronal ceroid lipofuscinosis;nuclear magnetic resonance imaging;priority journal;putamen;thalamus;white matter,"Autti, T.;Raininko, R.;Santavuori, P.;Vanhanen, S. L.;Poutanen, V. P.;Haltia, M.",1997,,,0,
5555,"Jansky-Bielschowsky variant disease: CT, MRI, and SPECT findings","Six patients with a variant type of Jansky-Bielschowsky (JBVD) disease were examined using 3 different imaging methods. Five of the patients underwent computed tomography, 4 magnetic resonance imaging, and 5 single photon emission computed tomography. All patients had brain atrophy that was most severe in the cerebellum. Magnetic resonance imaging demonstrated the parenchymal abnormalities well; all patients had hyperintense periventricular white matter, especially around the bodies and atria of the lateral ventricles, and a significant decrease in signal intensity in the thalami and/or putamina. Single photon emission computed tomography disclosed hypoperfusion of the cerebellum in all patients. Neuroimaging examinations are valuable in the diagnosis of JBVD. It may be difficult to divide patients with neuronal ceroid-lipofuscinosis disorders into clinical subtypes in the early stage of the disease. Magnetic resonance imaging, especially when combined with a typical clinical pattern, makes the diagnosis of JBVD highly likely. Radiologic examinations of the brain may also prove important in following the progression, as well as in investigating the pathophysiology, of the disease.",,"Autti, T.;Raininko, R.;Launes, J.;Nuutila, A.;Santavuori, P.",1992,1992,,0,
5556,Impaired renal function is associated with brain atrophy and poststroke cognitive decline,"OBJECTIVE: To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. METHODS: The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. RESULTS: Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl >/=60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041). CONCLUSIONS: Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention.",,"Auriel, E.;Kliper, E.;Shenhar-Tsarfaty, S.;Molad, J.;Berliner, S.;Shapira, I.;Ben-Bashat, D.;Shopin, L.;Tene, O.;Rosenberg, G. A.;Bornstein, N. M.;Ben Assayag, E.",2016,May 24,10.1212/wnl.0000000000002699,0,
5557,Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment,"OBJECTIVE: To test the hypothesis that depressive symptoms correlate with Alzheimer's disease (AD) type changes in CSF and structural and functional imaging including hippocampus volume, cortical thickness, white matter lesions, Diffusion tensor imaging (DTI), and fluoro-deoxy-glucose positron emission tomography (FDG-PET) in patient with subjective (SCI) and mild (MCI) cognitive impairment. METHOD: In 60 patients, depressive symptoms were assessed using the Geriatric Depression Scale. The subjects underwent MRI, 18F-FDG PET imaging, and lumbar CSF extraction. RESULTS: Subjects with depressive symptoms (n=24) did not have more pathological AD biomarkers than non-depressed. Uncorrected there were trends towards larger hippocampal volumes (P=0.06), less orbital WM damage measured by DTI (P=0.10), and higher orbital glucose metabolism (P=0.02) in the depressed group. The findings were similar when SCI and MCI were analyzed separately. Similarly, in patients with pathological CSF biomarkers (i.e., predementia AD, n=24), we found that correlations between scores on GDS and CSF Ass42 and P-tau indicated less severe AD-specific CSF changes with increasing depression. CONCLUSION: Depressive symptoms are common in SCI/MCI, but are not associated with pathological imaging or CSF biomarkers of AD. Depression can explain cognitive impairment in SCI/MCI or add to cognitive impairment leading to an earlier clinical investigation in predementia AD.",Adult;Aged;Alzheimer Disease/ cerebrospinal fluid/pathology/psychology/radionuclide imaging;Biomarkers/cerebrospinal fluid;Cerebral Cortex/pathology;Cognition Disorders/cerebrospinal fluid/pathology/psychology/radionuclide imaging;Depression/ cerebrospinal fluid/pathology/physiopathology/psychology/radionuclide;imaging;Diffusion Tensor Imaging/methods;Female;Fluorodeoxyglucose F18;Hippocampus/pathology/radionuclide imaging;Humans;Male;Middle Aged;Mild Cognitive Impairment/ cerebrospinal fluid/pathology/psychology/radionuclide;imaging;Positron-Emission Tomography/methods;Radiopharmaceuticals,"Auning, E.;Selnes, P.;Grambaite, R.;Saltyte Benth, J.;Haram, A.;Lovli Stav, A.;Bjornerud, A.;Hessen, E.;Hol, P. K.;Muftuler londalen, A.;Fladby, T.;Aarsland, D.",2015,Feb,10.1111/acps.12352,0,
5558,White matter integrity and cognition in Parkinson's disease: a cross-sectional study,"OBJECTIVE: We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson's disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer's disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance. METHODS: This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group. RESULTS: Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities. CONCLUSIONS: In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD.",Aged;Alzheimer Disease/etiology/pathology;Cognition Disorders/etiology/pathology;Cross-Sectional Studies;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged;Parkinson Disease/complications/ pathology;White Matter/ pathology,"Auning, E.;Kjaervik, V. K.;Selnes, P.;Aarsland, D.;Haram, A.;Bjornerud, A.;Hessen, E.;Esnaashari, A.;Fladby, T.",2014,,10.1136/bmjopen-2013-003976,0,
5559,Diffusion tensor MRI as a biomarker in axonal and myelin damage,"Diffusion tensor imaging has been used extensively as a research tool to understand the structural changes associated with white matter pathology. Using water diffusion as the basis to construct anatomic details, diffusion tensor imaging offers the potential to identify structural and functional adaptations before gross anatomical changes, such as lesions and tumors, become apparent on conventional MRI. Over the past 10 years, further parameters, such as axial and radial diffusivity, have been developed to characterize white matter changes specific to axons and myelin. In this paper, the potential application and outstanding issues on the use of diffusion tensor imaging directional diffusivity as a biomarker in axonal and myelin damage in neurological disorders will be reviewed.",,"Aung, W. Y.;Mar, S.;Benzinger, T. L.",2013,Oct 1,10.2217/iim.13.49,0,
5560,"Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI","The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in the detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm x 1 mm x 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 mum x 120 mum x 120 mum) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0mm for the left hemispheres (n=7) and 3.2mm for the right hemispheres (n=7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of the perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis.","Aged;Algorithms;Artificial Intelligence;Cadaver;Female;Humans;Image Enhancement/methods;Image Interpretation, Computer-Assisted/ methods;Magnetic Resonance Imaging/ methods;Male;Nerve Net/ anatomy & histology;Pattern Recognition, Automated/ methods;Reproducibility of Results;Sensitivity and Specificity;Temporal Lobe/ anatomy & histology","Augustinack, J. C.;Huber, K. E.;Stevens, A. A.;Roy, M.;Frosch, M. P.;van der Kouwe, A. J.;Wald, L. L.;Van Leemput, K.;McKee, A. C.;Fischl, B.",2013,Jan 1,10.1016/j.neuroimage.2012.08.071,0,
5561,Altered white and gray matter metabolism in CADASIL: a proton MR spectroscopy and 1H-MRSI study,"OBJECTIVE: Subcortical white matter hyperintensities (WMH) and small cystic lesions are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy causing stroke in young adults. To further characterize the cerebral pathology in vivo we analyzed metabolite concentrations in normal and abnormal appearing brain tissue using single and multiple voxel proton MR spectroscopy (1H-MRS and 1H-MRSI). METHODS: Twenty patients with CADASIL and 21 age-matched controls were studied with 1H-MRSI at the level of the centrum semiovale; short echo time 1H-MRS was performed in six patients (WMH) and 10 controls. LCModel fits were used to estimate absolute and relative concentrations of N:-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr) within WMH, normal appearing white matter (NAWM), and cortical gray matter (GM) as well as myo-inositol (mI) and lactate in WMH. RESULTS: 1H-MRSI-Patients with CADASIL showed significantly reduced NAA, Cho, Cr, and total metabolite content (Met(tot)) in WMH and NAWM. Normalization to Met(tot) revealed that NAA/Met(tot) was reduced in all regions, whereas Cho and Cr were relatively elevated in WMH. Short echo time 1H-MRS showed decreased NAA, Cr, Met(tot), and NAA/Met(tot) and elevated mI/Met(tot) and lactate in WMH. Metabolite changes were larger in severely affected subjects. Rankin scores correlated negatively with NAA/Met(tot) (all regions) and NAA/Cho (WMH), and positively with Cho/Met(tot) (WMH) and Cr/Met(tot) (NAWM). CONCLUSION: Marked metabolic abnormalities were observed in abnormal and normal appearing white matter in patients with CADASIL. The findings suggest axonal injury, enlarged extracellular spaces, myelin loss, and gliosis. The cortical abnormalities may reflect structural damage or functional neuronal impairment secondary to white matter pathology. NAA reductions were correlated with clinical disability emphasizing the clinicopathologic relevance of axonal injury in CADASIL.","Adult;Aged;Brain/*metabolism/*pathology;Dementia, Multi-Infarct/*metabolism/*pathology;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy;Male;Middle Aged;Protons","Auer, D. P.;Schirmer, T.;Heidenreich, J. O.;Herzog, J.;Putz, B.;Dichgans, M.",2001,Mar 13,,0,
5562,Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison,"PURPOSE: To differentiate lesion patterns in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from those in patients with sporadic subcortical arteriosclerotic encephalopathy (sSAE). MATERIALS AND METHODS: Magnetic resonance (MR; T2-weighted and fluid-attenuated inversion-recovery) images obtained in 28 patients with CADASIL were compared with images obtained in 24 patients with sSAE by using an automated pixel-based group comparison with statistical parametric mapping and regional semiquantitative rating. RESULTS: Visual rating showed higher lesion scores for CADASIL in the temporal and temporopolar white matter (WM). Statistical parametric mapping group analysis independently revealed more extensive bilateral involvement of the anterior temporal and superior frontal WM in CADASIL. There were bilateral signal intensity reductions within the dentate nucleus, deep cerebellar WM, crus cerebri, and thalamus. Lesions extended remarkably more often into arcuate fibers in the temporopolar and paramedian superior frontal lobes in CADASIL. Linear discriminant analysis was used to classify 96% (50 of 52) of the cases correctly, with temporopolar WM and arcuate fiber involvement contributing most to the discrimination function. CONCLUSION: The presented MR imaging criteria are useful in the diagnostic work-up in patients with leukoencephalopathy and help to differentiate CADASIL from sSAE. The observed pattern of vulnerability in CADASIL suggests future directions for research in the pathophysiology of this disorder. In addition, the study demonstrates the potential of automated image analysis to explore MR imaging lesion patterns.","Aged;Brain/ pathology;Case-Control Studies;Cerebral Infarction/epidemiology/genetics/ pathology;Dementia, Multi-Infarct/epidemiology/genetics/ pathology;Diagnosis, Differential;Discriminant Analysis;Female;Genes, Dominant;Humans;Image Processing, Computer-Assisted;Intracranial Arteriosclerosis/epidemiology/genetics/ pathology;Magnetic Resonance Imaging;Male;Middle Aged","Auer, D. P.;Putz, B.;Gossl, C.;Elbel, G.;Gasser, T.;Dichgans, M.",2001,Feb,10.1148/radiology.218.2.r01fe24443,0,
5563,Single stroke dementia: insights from 12 cases in Singapore,"BACKGROUND: Vascular dementia (VaD) is occasionally caused by a single, strategically located stroke. In this report, we describe the clinical and anatomical features of 12 cases of strategic single infarct dementia (SSID) from Singapore. METHODS: Each patient completed a standardized diagnostic evaluation including history, neurological and neuropsychological examination, laboratory testing, and brain imaging. Dementia was diagnosed using the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-III-R) criteria, and VaD was diagnosed using the National Institute of Neurologic Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria. VaD patients whose brain imaging study revealed a single cerebrovascular event were diagnosed with SSID. RESULTS: We identified 12 cases of SSID among 125 VaD patients (9.6%). Stroke mechanism was lacunar infarction in five cases, embolism in four cases, large vessel thrombosis in two cases, and parenchymal hemorrhage in one case. The most commonly impaired cognitive domains on neuropsychological testing were visual memory, visuoconstruction, and language. In 11 of the 12 SSID cases, the stroke was located in the left hemisphere. The thalamus, either alone or as the proximal portion of a posterior cerebral artery infarction, was involved in 8 of the 12 cases. Stroke locations in the nonthalamic SSID cases included left angular gyrus, subcortical left frontal lobe including minor forceps, left basal forebrain and medial frontal lobe plus anterior corpus callosum (proximal anterior cerebral artery infarction), and anterior corpus callosum alone. CONCLUSIONS: Various stroke mechanisms may produce SSID. In our SSID cases, vascular damage almost always involved the left hemisphere and frequently involved the thalamus and major interhemispheric or intrahemispheric white matter pathways.","Aged;Aged, 80 and over;Brain/pathology;Databases, Factual;Dementia/ etiology/pathology/ psychology;Female;Functional Laterality/physiology;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Psychiatric Status Rating Scales;Singapore;Stroke/ complications/pathology/ psychology","Auchus, A. P.;Chen, C. P.;Sodagar, S. N.;Thong, M.;Sng, E. C.",2002,Nov 15,,0,
5564,Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study,"OBJECTIVE: To examine the relationship between white matter hyperintensity (WMH) volume on magnetic resonance images and cognitive tests in a large, population-based sample. METHODS: Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort. The WMH volume relative to total cranial volume was computed; WMH volumes more than 1 SD above the age-predicted mean were defined as large. Adjusting for age, sex, education, height, and Framingham Stroke Risk Profile, we examined the relationship between WMH and 3 cognitive factors derived from a neuropsychological test battery (verbal memory, visuospatial memory and organization, and visual scanning and motor speed) and 3 individual measures of new learning, abstract reasoning, and naming. RESULTS: Compared with those with no or little WMH volume, participants with large WMH volume performed worse on the cognitive factors of visuospatial memory and organization (P = .04) and visual scanning and motor speed (P = .01), as well as on new learning (P = .04), but not on verbal memory (P = .52). CONCLUSIONS: In this younger community-based population of nondemented individuals, those with large WMH volume, as compared with those with less or no WMH volumes, performed significantly worse in cognitive domains generally associated with frontal lobe systems and, to a lesser extent, the medial temporal area. Further study will clarify whether large WMH volume and associated cognitive impairment lead to future risk of stroke or dementia.",Age Factors;Aged;Brain/ pathology;Cognition Disorders/ etiology/ pathology;Cohort Studies;Female;Humans;Magnetic Resonance Imaging;Male;Memory Disorders;Middle Aged;Visual Perception,"Au, R.;Massaro, J. M.;Wolf, P. A.;Young, M. E.;Beiser, A.;Seshadri, S.;D'Agostino, R. B.;DeCarli, C.",2006,Feb,10.1001/archneur.63.2.246,0,
5565,Multifocal Cerebral and Bilateral Middle Cerebellar Peduncle Infarctions in CADASIL,,Notch3 receptor;adult;ataxic gait;brain ischemia;CADASIL;case report;cerebellum infarction;cerebrovascular accident;clinical feature;cognitive defect;differential diagnosis;diffusion weighted imaging;executive function;human;lacunar stroke;male;mental instability;middle aged;middle cerebellar peduncle;migraine with aura;note;nuclear magnetic resonance imaging;patient;priority journal;transient ischemic attack,"Au, K.;Appireddy, R.;Barber, P. A.",2016,,,0,
5566,Genetic variation in white matter hyperintensity volume in the Framingham study,"Background and Purpose-In a previous study of normal elderly male twins, the heritability of quantitative white matter hyperintensity (WMH) volume has been estimated to be high (0.73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age. Methods-Brain magnetic resonance scans were performed on 2012 individuals in the cohort and offspring of the Framingham study. This report was limited to 1330 stroke-free and dementia-free members (mean age 61.0 years) of the Framingham offspring. Individuals with a history of multiple sclerosis, stroke, dementia, or other neurological condition including traumatic brain injury were excluded from this analysis. WMH volume and total cranial volume (TCV) were quantified using a previously published algorithm. Because of extreme skewing, measures of WMH were log-transformed before analysis. Variance components methods were used to estimate heritability of WMH after adjusting for sex, age, age2, and TCV. Results-In the full dataset, WMH heritability was 0.55 (P<0.0001). Heritability among women was 0.78 (P<0.0001) whereas heritability among men was 0.52 (P<0.0003). Heritability varied as average age increased, with a peak of 0.68 (P<0.0001) in individuals aged 55 or older. Conclusion-Using a family-based study design comprising generally healthy individuals, this study found high heritability of WMH overall and similar heritability for both men and women. In addition, the heritability of WMH remained high among individuals in whom the prevalence of cerebrovascular brain injury was generally low, suggesting that WMH is also likely to be an excellent genetic marker of brain aging.",adult;age;aged;aging;article;brain injury;dementia;female;genetic marker;genetic variability;human;major clinical study;male;multiple sclerosis;nuclear magnetic resonance imaging;priority journal;sex difference;cerebrovascular accident;white matter,"Atwood, L. D.;Wolf, P. A.;Heard-Costa, N. L.;Massaro, J. M.;Beiser, A.;D'Agostino, R. B.;DeCarli, C.",2004,,,0,
5567,"Phase II study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, quality of life, and mood","Ginkgo biloba has been reported to improve cognitive function in older adults and patients with Alzheimer's disease and multi-infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors. Eligibility criteria included: life expectancy >/=30 weeks, partial or whole brain radiation >/=6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, or stable or decreasing steroid dose, and no brain tumor treatment planned while on study. The Ginkgo biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States, Mini-Mental Status Exam, Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test, Modified Rey Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II, and the F-A-S Test. RESULTS: Of the 34 patients enrolled on study, 23 (68 %) completed 12 weeks of treatment and 19 (56 %) completed 24 weeks of treatment. There were significant improvements at 24 weeks in: executive function (TMT-B) (p = 0.007), attention/concentration (TMT-A) (p = 0.002), and non-verbal memory (ROCF-immediate/delayed recall) (p = 0.001/0.002), mood (p = 0.002), FACT-Br subscale (p = 0.001), and the FACT physical subscale (p = 0.003). CONCLUSIONS: Some improvement in quality of life and cognitive function were noted with Ginkgo biloba. However, treatment with Ginkgo biloba was associated with a high dropout rate.","Adult;Aged;Aged, 80 and over;Analysis of Variance;Brain Neoplasms/complications/drug therapy/psychology;Cognition Disorders/drug therapy/etiology/psychology;Female;Follow-Up Studies;Ginkgo biloba;Humans;Male;Middle Aged;Mood Disorders/drug therapy/etiology/psychology;Neuropsychological Tests;Phytotherapy/ methods;Plant Preparations/ therapeutic use;Quality of Life;Severity of Illness Index;Time Factors","Attia, A.;Rapp, S. R.;Case, L. D.;D'Agostino, R.;Lesser, G.;Naughton, M.;McMullen, K.;Rosdhal, R.;Shaw, E. G.",2012,Sep,10.1007/s11060-012-0901-9,0,
5568,Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice,"This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as the etiology for a frontal/dysexecutive syndrome). The potential clinical utility of other promising methods, whether already approved for use (e.g., amyloid PET) or as yet only used in research (e.g., tau PET, functional MRI, diffusor tensor imaging), remains to be proven for widespread use in community practice. However, these constitute unreimbursed third-tier options that merit further study for clinical and cost-effective utility. In the future, combination use of imaging methods will likely improve diagnostic accuracy.",Alzheimer's disease;Ct;Dementia with Lewy Bodies;Frontotemporal Dementia;Mri;Pet;Spect;cognitive impairment;neuroimaging;vascular cognitive impairment,"Atri, A.",2016,,10.1016/b978-0-444-53486-6.00050-8,0,
5569,Hypertension and neuronal degeneration in excised rat spinal cord studied by high-b value q-space diffusion magnetic resonance imaging,"Hypertension is one of the major risk factors of stroke and vascular dementia (VaD). We used stroke prone spontaneous hypertensive rats (SPSHRs) as a model for neuronal degeneration frequently occurring in humans with vascular disease. Recently, high b value q-space diffusion-weighted imaging (DWI) was shown to be very sensitive to the pathophysiological state of the white matter. We studied the spinal cords of SPSHR rats ex vivo after the appearance of motor impairments using diffusion anisotropy and q-space diffusion imaging (measured at a high b value of up to 1 x 10(5) s/mm(2)). The diffusion anisotropy images computed from low b value data set (b(max) approximately 2500 s/mm(2)) showed a small but statistically significant decrease (approximately 12%, P < 0.05) in the diffusion anisotropy in the spinal cords of the SPSHR group as compared to control rats. However, more significant changes were found in the high b value q-space diffusion images. The q-space displacement values in the white matter of the SPSHR group were found to be higher by more than 70% (P < 0.002) than that of the control group. These observations concurred with electron microscopy (EM) that showed significant demyelination in the spinal cords of the SPSHR group. These results seem to indicate that high b value q-space DWI might be a sensitive method for following demyelination and axonal loss associated with vascular insults.","Animals;Anisotropy;Diffusion Magnetic Resonance Imaging;Hypertension/ physiopathology;Male;Microscopy, Electron;Nerve Degeneration/ physiopathology;Organ Culture Techniques;Rats;Rats, Inbred SHR;Spinal Cord/ pathology/ radiography/ultrastructure","Assaf, Y.;Mayk, A.;Eliash, S.;Speiser, Z.;Cohen, Y.",2003,Dec,10.1016/s0014-4886(03)00274-7,0,
5570,"Segmentation and feature extraction techniques, with applications to MRI head studies","To obtain a three-dimensional reconstruction of the hippocampus from a volumetric MRI head study, it is necessary to separate that structure not only from the surrounding white matter, but also from contiguous areas of gray matter-the amygdala and cerebral cortex. At present it is necessary for a physician to manually segment the hippocampus on each slice of the volume to obtain such a reconstruction. This process is time consuming, and is subject to inter- and intra-operator variation as well as large discontinuities between slices. We propose a novel technique, making use of a combination of gray scale and edge-detection algorithms and some a priori knowledge, by which a computer may make an unsupervised identification of a given structure through a series of contiguous images. This technique is applicable even if the structure includes so-called false contours or missing contours. Applications include three-dimensional reconstruction of difficult- to-segment regions of the brain, and volumetric measurements of structures from series of two-dimensional images.",,"Ashton, E. A.;Berg, M. J.;Parker, K. J.;Weisberg, J.;Chang Wen, C.;Ketonen, L.",1995,1995,,0,
5571,Recurrent stroke and multi-infarct dementia in systemic lupus erythematosus: Association with antiphospholipid antibodies,"Four patients with recurrent stroke and multi-infarct dementia are presented in whom the dementia was progressive and severe. Three of the patients developed the dementia during the course of an illness which was punctuated by repeated episodes of cerebral infarction demonstrated by computed tomographic (CT) scans. The fourth patient presented with an illness dominated by progressive and deteriorating higher mental functions, which culminated in a major stroke 18 months later. Three patients fulfilled the American Rheumatism Association (ARA) criteria for the classification of systemic lupus erythematosus, the fourth had a 'lupus-like' disease. All had livedo reticularis, severe migraines, and also demonstrated antibodies to phospholipids. All four patients suffered deep vein thromboses.",phospholipid antibody;case report;central nervous system;cerebrovascular accident;computer assisted tomography;dementia;diagnosis;etiology;human;livedo reticularis;migraine;peripheral vascular system;priority journal;systemic lupus erythematosus,"Asherson, R. A.;Mercey, D.;Phillips, G.",1987,,,0,
5572,Deficits in sentence expression in amyotrophic lateral sclerosis,"Quantitative examinations of speech production in amyotrophic lateral sclerosis (ALS) are rare. To identify language features minimally confounded by a motor disorder, we investigated linguistic and motor sources of impaired sentence expression in ALS, and we related deficits to gray matter (GM) and white matter (WM) MRI abnormalities. We analyzed a semi-structured speech sample in 26 ALS patients and 19 healthy seniors for motor- and language-related deficits. Regression analyses related grammaticality to GM atrophy and reduced WM fractional anisotropy (FA). Results demonstrated that ALS patients were impaired relative to controls on quantity of speech, speech rate, speech articulation errors, and grammaticality. Speech rate and articulation errors were related to the patients' motor impairment, while grammatical difficulty was independent of motor difficulty. This was confirmed in subgroups without dysarthria and without executive deficits. Regressions related grammatical expression to GM atrophy in left inferior frontal and anterior temporal regions and to reduced FA in superior longitudinal and inferior frontal-occipital fasciculi. In conclusion, patients with ALS exhibit multifactorial deficits in sentence expression. They demonstrate a deficit in grammatical expression that is independent of their motor disorder. Impaired grammatical expression is related to disease in a network of brain regions associated with syntactic processing.","Aged;Amyotrophic Lateral Sclerosis/*complications;Brain/*pathology;Female;Humans;Imaging, Three-Dimensional;Language Disorders/diagnosis/*etiology/*pathology;Linguistics;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Dementia;aphasia;cognitive neuropsychology;language;speech","Ash, S.;Olm, C.;McMillan, C. T.;Boller, A.;Irwin, D. J.;McCluskey, L.;Elman, L.;Grossman, M.",2015,Mar,10.3109/21678421.2014.974617,0,
5573,Differentiating primary progressive aphasias in a brief sample of connected speech,"Objective: A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA. Methods: We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality.We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits. Results: We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant. Conclusions: These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics. © 2013 American Academy of Neurology.",,"Ash, S.;Evans, E.;O'Shea, J.;Powers, J.;Boller, A.;Weinberg, D.;Haley, J.;McMillan, C.;Irwin, D. J.;Rascovsky, K.;Grossman, M.",2013,23,,0,
5574,Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment,"Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.",aged;aging;article;brain size;clinical evaluation;cognition;cohort analysis;community living;depth perception;educational status;episodic memory;female;gray matter volume;human;imaging software;male;nervous system parameters;neuroimaging;normal human;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;priority journal;semantic memory;white matter;white matter hyperintensity;working memory;1.5 Tesla;FreeSurfer,"Arvanitakis, Z.;Fleischman, D. A.;Arfanakis, K.;Leurgans, S. E.;Barnes, L. L.;Bennett, D. A.",2016,,10.1007/s00429-015-1034-7,0,5575
5575,Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment,"Both presence of white matter hyperintensities (WMH) and smaller total gray matter volume on brain magnetic resonance imaging (MRI) are common findings in old age, and contribute to impaired cognition. We tested whether total WMH volume and gray matter volume had independent associations with cognition in community-dwelling individuals without dementia or mild cognitive impairment (MCI). We used data from participants of the Rush Memory and Aging Project. Brain MRI was available in 209 subjects without dementia or MCI (mean age 80; education = 15 years; 74 % women). WMH and gray matter were automatically segmented, and the total WMH and gray matter volumes were measured. Both MRI-derived measures were normalized by the intracranial volume. Cognitive data included composite measures of five different cognitive domains, based on 19 individual tests. Linear regression analyses, adjusted for age, sex, and education, were used to examine the relationship of logarithmically-transformed total WMH volume and of total gray matter volume to cognition. Larger total WMH volumes were associated with lower levels of perceptual speed (p < 0.001), but not with episodic memory, semantic memory, working memory, or visuospatial abilities (all p > 0.10). Smaller total gray matter volumes were associated with lower levels of perceptual speed (p = 0.013) and episodic memory (p = 0.001), but not with the other three cognitive domains (all p > 0.14). Larger total WMH volume was correlated with smaller total gray matter volume (p < 0.001). In a model with both MRI-derived measures included, the relation of WMH to perceptual speed remained significant (p < 0.001), while gray matter volumes were no longer related (p = 0.14). This study of older community-dwelling individuals without overt cognitive impairment suggests that the association of larger total WMH volume with lower perceptual speed is independent of total gray matter volume. These results help elucidate the pathological processes leading to lower cognitive function in aging.",,"Arvanitakis, Z.;Fleischman, D. A.;Arfanakis, K.;Leurgans, S. E.;Barnes, L. L.;Bennett, D. A.",2015,Apr 2,10.1007/s00429-015-1034-7,0,
5576,Objectification and quantification of the cognitive impairment from an existing HIV infection or HIV encephalopathy using magnetic resonance spectroscopy,"Some patients with HIV develop dementia. Using in vivo proton nuclear magnetic resonance (1H-NMR) spectroscopy, it is possible to measure the metabolic changes noninvasively. In this study, it is of interest to answer the clinically relevant question of whether magnetic resonance spectroscopy is suitable for the diagnosis of HIV encephalopathy. In total, 14 HIV-positive patients were investigated by means of localized 1H-NMR spectroscopy in the following locations: (1) the mid-parietal gray matter, (2) the parietal white matter (PWM), and (3) the frontal white matter. All patients had no other brain diseases, apart from the HIV encephalopathy. The clinical extent of HIV encephalopathy of each patient was investigated using the following tests: (1) an electroencephalogram, (2) a neurological examination and psychiatric assessment, and (3) a psychometrical test. The spectroscopic changes in the PWM were more pronounced than those in the cortex, and the myo-inositol/creatine (mI/Cr) signal showed a clear increase in the cortex. Overall, the mI/Cr ratio emerged as the most reliable and earliest parameter to indicate an HIV encephalopathy. © The Author(s) 2012.",creatine;inositol;lamivudine;nelfinavir;proteinase inhibitor;zidovudine;article;clinical article;cognitive defect;controlled study;disease duration;early diagnosis;electroencephalogram;female;Fourier transformation;gray matter;highly active antiretroviral therapy;HIV associated dementia;human;Human immunodeficiency virus infected patient;Human immunodeficiency virus infection;intelligence quotient;male;neuroimaging;neurologic examination;nuclear magnetic resonance scanner;priority journal;proton nuclear magnetic resonance;psychologic assessment;psychometry;survival;white matter;Magnetom Vision,"Arneth, B.;Pilatus, U.;Lanfermann, H.;Enzensberger, W.",2013,,,0,
5577,A new method for the relative quantification of rCBF examined by 99Tcm-HMPAO SPECT,"A new method for the analysis of regional cerebral blood flow (rCBF) studies, the 'Min-Max' method, was compared with the conventional method, the 'Average' method. Regional CBF was examined by single photon emission computed tomography (SPECT) using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO). The two methods were used to quantify the rCBF in a population of patients with various dementia disorders, and in healthy controls. Results from a phantom were also used. In the Average method the average counts per pixel (cp-1) within irregular manually drawn regions of interest (ROIs) was registered. In the Min-Max method the minimum cp-1 and maximum cp-1 within rectangular ROIs were registered for white and grey matter, respectively. The relative rCBF (rrCBF) was calculated as the ratio between the regional and cerebellar values. The Min-Max method gave systematically lower values for rrCBF in the white matter, in both clinical studies, and in the phantom, compared to the Average method. No difference was found in the grey matter results. The variability in rrCBF in the phantom study was greater with the Min-Max method than with the Average method, but this effect was counteracted in the clinical studies by a smaller interobserver error. The average regional differences between patients and controls appeared greater with the Min-Max method than with the Average method. The Min-Max method proved to be more simple to execute, involved a smaller observer error, and with respect to ability to distinguish patients with dementia disorders from controls, it appears to function at least as well as the accepted Average method.","Adult;Aged;Aged, 80 and over;Alzheimer Disease/physiopathology/radionuclide imaging;Cerebrovascular Circulation/*physiology;Dementia/physiopathology/*radionuclide imaging;Dementia, Multi-Infarct/physiopathology/radionuclide imaging;Humans;Hydrocephalus, Normal Pressure/physiopathology/radionuclide imaging;Middle Aged;Models, Structural;*Organotechnetium Compounds;*Oximes;Regional Blood Flow/physiology;Technetium Tc 99m Exametazime;Tomography, Emission-Computed, Single-Photon/*methods","Arlig, A.;Larsson, A.;Bergh, A. C.;Jacobsson, L.;Wikkelso, C.",1994,Oct,,0,
5578,Ultrastructural cutaneous microvascular pathology of young adults aged up to 50 years with chronic kidney disease and vascular cognitive impairment,"BACKGROUND: Studies suggest a link between chronic kidney disease and cognitive impairment. Skin biopsy is hire in the study of leucoaraiosis since permit establish the responsible vascular pathology of subcortical white matter changes because the pathological hallmark is systemic. The aim was to study the ultrastructural changes of cutaneous small vessel of patients aged up to 50 years with chronic kidney disease (CKD) and vascular cognitive impairment (VCI). METHODS: Clinical, laboratorial, cerebral imaging, neuropsycological evaluation for executive functions (Clox test), and skin biopsy to 4 patients aged up to 50 years with CKD and VCI were done. Skin biopsy was prepared for conventional transmission electron microscopy study. RESULTS: Clinical diagnosis included hypertension, diabetes, and CKD in all cases. All cases developed VCI in a relatively short period. Small vessels study revealed small vessel disease type-degenerative microangiopathy. The principal findings were increase of wall-lumen ratio, thickened basal membrane, and collagen fibers proliferation. CONCLUSIONS: Cutaneous degenerative microangiopathy is matched with cerebral microvascular pathology and could be important for the development of cognitive impairment in young adults with CKD. The characterization of microvascular pathology in skin biopsies, in this type of patients, could contribute to the knowledge of some pathophysiological and therapeutical topics and possibly be useful in clinical setting. Added patients are needed to establish a complete characterization of microangiopathy.","Adult;Brain/pathology;Cognition Disorders/complications/ pathology/physiopathology;Dementia, Vascular/complications/ pathology/physiopathology;Diabetes Mellitus, Type 2/complications/pathology/physiopathology;Female;Humans;Kidney Failure, Chronic/complications/ pathology/physiopathology;Magnetic Resonance Imaging;Male;Microscopy, Electron, Transmission/methods;Microvessels/ ultrastructure;Middle Aged;Neuropsychological Tests;Skin/ blood supply","Arismendi-Morillo, G.;Fernandez-Abreu, M.",2010,Aug,10.3109/01913121003743690,0,
5579,Automated method for identification of patients with Alzheimer's disease based on three-dimensional MR images,"RATIONALE AND OBJECTIVES: An automated method for identification of patients with cerebral atrophy due to Alzheimer's disease (AD) was developed based on three-dimensional (3D) T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: Our proposed method consisted of determination of atrophic image features and identification of AD patients. The atrophic image features included white matter and gray matter volumes, cerebrospinal fluid (CSF) volume, and cerebral cortical thickness determined based on a level set method. The cortical thickness was measured with normal vectors on a voxel-by-voxel basis, which were determined by differentiating a level set function. The CSF spaces within cerebral sulci and lateral ventricles (LVs) were extracted by wrapping the brain tightly in a propagating surface determined with a level set method. Identification of AD cases was performed using a support vector machine (SVM) classifier, which was trained by the atrophic image features of AD and non-AD cases, and then an unknown case was classified into either AD or non-AD group based on an SVM model. We applied our proposed method to MR images of the whole brains obtained from 54 cases, including 29 clinically diagnosed AD cases (age range, 52-82 years; mean age, 70 years) and 25 non-AD cases (age range, 49-78 years; mean age, 62 years). RESULTS: As a result, the area under a receiver operating characteristic (ROC) curve (Az value) obtained by our computerized method was 0.909 based on a leave-one-out test in identification of AD cases among 54 cases. CONCLUSION: This preliminary result showed that our method may be promising for detecting AD patients.","Aged;Aged, 80 and over;Algorithms;Alzheimer Disease/cerebrospinal fluid/ diagnosis/pathology;Area Under Curve;Atrophy;Brain/ pathology;Case-Control Studies;Cerebral Cortex/pathology;Expert Systems;Female;Humans;Image Interpretation, Computer-Assisted/ methods;Image Processing, Computer-Assisted/methods;Imaging, Three-Dimensional/ methods;Lateral Ventricles/pathology;Magnetic Resonance Imaging/ methods;Male;Middle Aged;ROC Curve","Arimura, H.;Yoshiura, T.;Kumazawa, S.;Tanaka, K.;Koga, H.;Mihara, F.;Honda, H.;Sakai, S.;Toyofuku, F.;Higashida, Y.",2008,Mar,10.1016/j.acra.2007.10.020,0,
5580,A hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex,"We report a 29-year-old male hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex, who died 2.5 months after the onset of dementia. The patient's cognitive abnormalities including forgetfulness, loss of concentration and slowing of thought appeared about 7 years after HIV infection. His neurological symptoms were characterized as progressive dementia, episodic consciousness loss, transverse myelopathy and peripheral neuropathy. He had generalized slow waves in electroencephalogram (EEG), progressive cerebral atrophy and a diffuse high intensity lesion in the white matter as shown by T2-weighted brain magnetic resonance imaging (MRI). We emphasize the significance of neurological complications, especially acute progressive dementia, in Japanese patients with acquired immunodeficiency syndrome (AIDS).",,"Arimura, H.;Nakagawa, M.;Maruyama, Y.;Arimura, K.;Osame, M.",1995,1995,,0,
5581,Associations between level and change in physical function and brain volumes,"Background: Higher levels of fitness or physical function are positively associated with cognitive outcomes but the potential underlying mechanisms via brain structure are still to be elucidated in detail. We examined associations between brain structure and physical function (contemporaneous and change over the previous three years) in community-dwelling older adults. Methodology/Principal Findings: Participants from the Lothian Birth Cohort 1936 (N=694) underwent brain MRI at age 73 years to assess intracranial volume, and the volumes of total brain tissue, ventricles, grey matter, normal-appearing white matter, and white matter lesions. At ages 70 and 73, physical function was assessed by 6-meter walk, grip strength, and forced expiratory volume. A summary 'physical function factor' was derived from the individual measures using principal components analysis. Performance on each individual physical function measure declined across the three year interval (p<0.001). Higher level of physical function at ages 70 and 73 was associated with larger total brain tissue and white matter volumes, and smaller ventricular and white matter lesion volumes (standardized β ranged in magnitude from 0.07 to 0.17, p<0.001 to 0.034). Decline in physical function from age 70 to 73 was associated with smaller white matter volume (0.08, p<0.01, though not after correction for multiple testing), but not with any other brain volumetric measurements. Conclusions/Significance: Physical function was related to brain volumes in community-dwelling older adults: declining physical function was associated with less white matter tissue. Further study is required to explore the detailed mechanisms through which physical function might influence brain structure, and vice versa. © 2013 Aribisala et al.",aged;article;brain size;brain tissue;brain ventricle;cohort analysis;controlled study;exercise test;female;forced expiratory volume;functional assessment;gray matter;grip strength;human;major clinical study;male;neuroanatomy;nuclear magnetic resonance imaging;nuclear magnetic resonance scanner;physical activity;physical performance;walking;white matter;white matter lesion;GE Signa Horizon HDx 1.5 T,"Aribisala, B. S.;Gow, A. J.;Bastin, M. E.;Valdés Hernández, M. D. C.;Murray, C.;Royle, N. A.;Maniega, S. M.;Starr, J. M.;Deary, I. J.;Wardlaw, J. M.",2013,,,0,
5582,Rapidly progressing dementia as the presenting symptom of Waldenström's macroglobulinemia: Findings from magnetic resonance imaging of the brain in Bing-Neel syndrome,"Case report. A 68-year-old male with no relevant clinical history was admitted to hospital because of symptoms of cognitive impairment (attentional deficit, short-term memory disorders and behavioural disorders), accompanied by apraxia of gait and rectal and urinary incontinence. Results of a general clinical exploration were normal. In the MRI study of the brain numerous areas of hypersignal were observed in different arterial territories, which stood out in the T2, FLAIR and, above all, in diffusion-weighted sequences. Analytical studies showed hypergammaglobulinemia with monoclonal IgM-κ and a bone marrow biopsy revealed infiltration by plasmatic cells. Bing-Neel syndrome was diagnosed. Conclusions. We underline this exceptional form of presentation of Waldenström's macroglobulinemia and highlight the findings of diffusion-weighted MRI, which suggested multiple infarcts for which a neoplastic vascular obstruction mechanism similar to that involved in malignant angioendotheliomatosis is posited.",,"Arias, M.;Pereiro-Zabala, I.;Requena-Caballero, I.;Sesar-Ignacio, A.;Arias-Rivas, S.;Villamayor-Blanco, B.",2004,1,,0,
5583,Systemic inflammation in non-demented elderly human subjects: brain microstructure and cognition,"The purpose of this study was to test the hypothesis that higher levels of systemic inflammation in a community sample of non-demented subjects older than seventy years of age are associated with reduced diffusion anisotropy in brain white matter and lower cognition. Ninety-five older persons without dementia underwent detailed clinical and cognitive evaluation and magnetic resonance imaging, including diffusion tensor imaging. Systemic inflammation was assessed with a composite measure of commonly used circulating inflammatory markers (C-reactive protein and tumor necrosis factor-alpha). Tract-based spatial statistics analyses demonstrated that diffusion anisotropy in the body and isthmus of the corpus callosum was negatively correlated with the composite measure of systemic inflammation, controlling for demographic, clinical and radiologic factors. Visuospatial ability was negatively correlated with systemic inflammation, and diffusion anisotropy in the body and isthmus of the corpus callosum was shown to mediate this association. The findings of the present study suggest that higher levels of systemic inflammation may be associated with lower microstructural integrity in the corpus callosum of non-demented elderly individuals, and this may partially explain the finding of reduced higher-order visual cognition in aging.","Aged;Aged, 80 and over;Brain/ pathology;Cognition;Female;Humans;Magnetic Resonance Imaging;Male;Systemic Inflammatory Response Syndrome/ pathology","Arfanakis, K.;Fleischman, D. A.;Grisot, G.;Barth, C. M.;Varentsova, A.;Morris, M. C.;Barnes, L. L.;Bennett, D. A.",2013,,10.1371/journal.pone.0073107,0,
5584,Specific anatomic associations between white matter integrity and cognitive reserve in normal and cognitively impaired elders,"OBJECTIVES: to investigate the associations between white matter (WM) integrity and cognitive reserve (CR) in healthy elders (HE), amnestic mild cognitive impairment (a-MCI), and Alzheimer's disease (AD). The authors studied correlations between CR and WM integrity in regions showing WM age-related effects or pathologic changes and tested the differences of slopes between groups. METHODS: diffusion tensor images (DTIs) were obtained from 18 young individuals, 15 HE, 16 a-MCI cases, and 15 AD cases. Tract-based spatial statistics was used to process DTI data. Areas showing age-related fractional anisotropy (FA) shrinkages (HE < young) and pathology-related FA network ""(AD < HE)"" were defined. Correlations between CR and WM integrity were adjusted for age, gender, memory performance and brain volumes. RESULTS: he presented more negative correlations between CR and WM integrity than patients with a-MCI and AD in age-related areas, such as the genum of the corpus callosum. However, these results were mediated by normal variability in memory function and brain volumes. For patients with a-MCI, negative associations between CR and FA were found in several major tracts, being more robust than in AD group. Although longitudinal results need to be interpreted with caution because of the reduced sample of patients with MCI, after 2 years of follow-up, all patients who progressed to AD had high-CR scores, suggesting a putative link between reduced WM integrity (maximal in patients with high CR) and risk of progression to AD. CONCLUSIONS: CR correlates are implemented in different anatomic WM areas in HE and patients with a-MCI. Healthy elders with high CR may present better tolerance of typical age-related effects on WM integrity; in patients with a-MCI, the association may reflect increased capacity to cope with incipient cerebral damage.","Adult;Aged;Aging/ pathology/ psychology;Alzheimer Disease/ pathology/ psychology;Anisotropy;Atrophy/pathology/psychology;Brain/pathology;Cognition Disorders/ pathology/ psychology;Cognitive Reserve;Diffusion Tensor Imaging/methods;Female;Humans;Male;Nerve Fibers, Myelinated/ pathology;Neural Pathways/pathology","Arenaza-Urquijo, E. M.;Bosch, B.;Sala-Llonch, R.;Sole-Padulles, C.;Junque, C.;Fernandez-Espejo, D.;Bargallo, N.;Rami, L.;Molinuevo, J. L.;Bartres-Faz, D.",2011,Jan,10.1097/JGP.0b013e3181e448e1,0,
5585,"Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack","BACKGROUND AND PURPOSE: Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. METHODS: Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. RESULTS: In all, 234 patients were included, mean (+/-SD) age 65.7 +/- 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE </= 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE </= 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). CONCLUSION: In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment.","Aged;Atrophy/complications/diagnostic imaging/ pathology/psychology;Cerebral Small Vessel Diseases/complications/diagnostic;imaging/ pathology/psychology;Cognition/physiology;Cognitive Dysfunction/complications/ diagnosis/pathology/psychology;Female;Humans;Ischemic Attack, Transient/complications/diagnostic imaging/ pathology/psychology;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Stroke/complications/diagnostic imaging/ pathology/psychology;Temporal Lobe/diagnostic imaging/ pathology;Alzheimer's disease;cognitive disorders and dementia;medial temporal lobe atrophy;small vessel disease;stroke","Arba, F.;Quinn, T.;Hankey, G. J.;Ali, M.;Lees, K. R.;Inzitari, D.;Collaboration, Vista",2017,Feb,,0,
5586,Small vessel disease and clinical outcomes after IV rt-PA treatment,"INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age+/-SD=68.7+/-15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.","EC 3.4.21.68 (Tissue Plasminogen Activator);Aged;Aged, 80 and over;Cerebral Small Vessel Diseases/diagnostic imaging/ epidemiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Stroke/ complications/drug therapy/pathology;Tissue Plasminogen Activator/therapeutic use;clinical outcomes;intravenous thrombolysis;magnetic resonance;small vessel disease;stroke;white matter changes","Arba, F.;Inzitari, D.;Ali, M.;Warach, S. J.;Luby, M.;Lees, K. R.;Collaboration, Stir Vista Imaging",2017,Jul,,0,5587
5587,Small vessel disease and clinical outcomes after IV rt-PA treatment,"INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age+/-SD=68.7+/-15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.",clinical outcomes;intravenous thrombolysis;magnetic resonance;small vessel disease;stroke;white matter changes,"Arba, F.;Inzitari, D.;Ali, M.;Warach, S. J.;Luby, M.;Lees, K. R.;Collaboration, Stir Vista Imaging",2017,Feb 23,,0,
5588,Association of Coffee Consumption with MRI Markers and Cognitive Function: A Population-Based Study,"BACKGROUND: Coffee is one of the most widely consumed beverages worldwide and has been of considerable interest in research on cognition and dementia. OBJECTIVE: To investigate the effect of coffee on preclinical brain MRI markers of dementia and cognitive performance. METHODS: In 2,914 participants from the population-based Rotterdam Study (mean age: 59.3+/-7.2 years, 55% females), we assessed coffee consumption, performed brain MRI, and assessed cognition at baseline. To study cognitive change, cognitive assessment was repeated after 5 years of follow-up. Coffee consumption was analyzed continuously (per cup increase) and in categories (0-1, >1-3, >3 cups/day). Using logistic and linear regression, associations of coffee consumption with lacunar infarcts and brain tissue volumes on MRI, and cognitive performance (cross-sectional and longitudinal) were investigated, adjusting for relevant confounders. RESULTS: We found that higher coffee consumption was associated with a lower prevalence of lacunar infarcts [odds ratio per cup increase: 0.88 (95% CI:0.79;0.98)], and smaller hippocampal volume [difference: -0.01 (95% CI:-0.02;0.00)]. Also, we found that the highest category of coffee consumption was associated with better performance on the Letter Digit Substitution Task [difference: 1.13(95% CI:0.39;1.88)], Word Fluency test [0.74(95% CI:0.04,1.45)], Stroop interference task [1.82(95% CI:0.23;3.41)], and worse performance on the 15-Word Learning test delayed recall [-0.38(95% CI:-0.74;-0.02)]. These associations were not found when cognition was analyzed longitudinally. CONCLUSION: We found complex associations between coffee consumption, brain structure, and cognition. Higher coffee consumption was cross-sectionally associated with a lower occurrence of lacunar infarcts and better executive function, but also with smaller hippocampal volume and worse memory function.",Brain imaging;Mri;brain tissue;coffee consumption;cognitive function;epidemiology,"Araujo, L. F.;Mirza, S. S.;Bos, D.;Niessen, W. J.;Barreto, S. M.;van der Lugt, A.;Vernooij, M. W.;Hofman, A.;Tiemeier, H.;Ikram, M. A.",2016,May 3,10.3233/jad-160116,0,
5589,Imaging in Neurodegenerative Disorders,"This article discusses imaging findings of the cortical and subcortical neurodegenerative diseases. Spinocerebellar ataxia and neurodegenerative diseases secondary to vascular insults (multiinfarction dementia, Binswanger's disease, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and amyloid angiopathy) are beyond the scope of this discussion. © 2010 Elsevier Inc.",,"Aralasmak, A.;Kocak, M.",2010,April,,0,
5590,Membranous lipodystrophy: MR imaging appearance of the brain,"Five patients with membranous lipodystrophy (lipomembranous polycystic osteodysplasia with progressive dementia) underwent magnetic resonance (MR) imaging of the brain. T2-weighted MR images showed atrophied cerebral white matter with dilated ventricles; increased signal intensity of the white matter; and decreased signal intensity of the thalamus, putamen, caudate nucleus, and cerebral cortex. Although each single finding is not specific, the combination of the above MR findings when coupled with skeletal lesions strongly suggests this rare disease.",,"Araki, T.;Ohba, H.;Monzawa, S.;Sakuyama, K.;Hachiya, J.;Seki, T.;Takahashi, Y.;Yamaguchi, M.",1991,1991,,0,
5591,Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease,"Neuronal intranuclear inclusion disease (NIID) is an uncommon progressive neurodegenerative disorder. Adult-onset NIID can result in prominent dementia. We herein describe the case of a 74-year-old man who presented with dementia, cerebellar ataxia, neuropathy, and autonomic dysfunction. Diffusion-weighted imaging showed hyperintensity of the corticomedullary junction. Fluid-attenuated inversion recovery images showed frontal-dominant white matter hyperintensity. NIID was diagnosed from the presence of intranuclear inclusions in a skin biopsy sample. Neuropsychological testing revealed memory loss and frontal cognitive dysfunction, especially in relation to language and executive functions. We were therefore able to confirm the association of NIID with cognitive dysfunction.",,"Araki, K.;Sone, J.;Fujioka, Y.;Masuda, M.;Ohdake, R.;Tanaka, Y.;Nakamura, T.;Watanabe, H.;Sobue, G.",2016,,10.2169/internalmedicine.55.5544,0,
5592,Serial magnetic resonance angiography in a patient with angioinvasive aspergillosis,"Angioinvasive aspergillus can lead to acute infarction. A 74-year old man complained about mild weakness of the left limbs; based on diffusion-weighted magnetic resonance imaging, he was diagnosed with acute infarction in the right caudate and anterior limb of the internal capsule. After admission, he had a fever with disturbance of consciousness. Elevated serum β-D-glucan, elevated galactomannan antigen titers in cerebrospinal fluid and histopathological analysis on a biopsy specimen of the right sphenoid sinus enabled a diagnosis of Aspergillus infection. Serial magnetic resonance angiography showed the progressing stenosis of the major cerebral artery by angioinvasive aspergillosis with the spread of the cerebral infarction. Our case suggests that serial magnetic resonance angiography might be useful for monitoring progression of aspergillus vasculopathy.",,"Araki, K.;Ito, M.;Atsuta, N.;Katsuno, M.;Sobue, G.",2016,1,,0,
5593,[A case of non-atherothrombotic cerebroretinal small vessel disease],"There is an increasing interest in the relation between retinal artery abnormalities and cerebral small-vessel diseases (SVD), because retinal vessels share common properties with cerebral small vessels. We report a case of juvenile cerebrovascular disease presenting retinal vessel abnormalities, which clinically resembled cerebral autosomal dominant arteriopathy with stroke and ischemic leukoencephalopathy (CADASIL) but in which Notch3 gene mutations were not detected. A 42-year old woman was hospitalized at the department of Neurology in our hospital, complaining of headache and dysarthria. MRI showed bilateral spotted white matter lesions in the paraventricular area and the temporal lobe, and an ovoid lesion in the right corona radiata. Despite steroid pulse therapy, she developed right incomplete hemiparesis and new lesions were detected in the anterior temporal pole and external capsule. Her genetic analysis showed no mutations in the Notch 3 gene. Ophthalmological examination revealed arterial sheathing in the peripapillary region. Fluorescein angiography showed narrowing of the retinal arterioles and distinguished a peripheral vascular network. In this case, ophthalmological examination revealed retinal vessel abnormalities in a relatively young woman with no risk factors such as hypertention or artheriosclerosis, presenting recurrent subcortical strokes. This actual case indicates the association between retinal vessel abnormalities and cerebral SVDs.",adult;article;CADASIL;case report;cerebrovascular disease;differential diagnosis;female;human;retina blood vessel;retina disease,"Arakawa, N.;Kashii, S.;Washida, K.;Kaneda, D.;Masai, H.;Hiroi, K.;Taguchi, H.;Fujiwara, K.",2011,,,0,
5594,"Clinicopathological study on a case of neuro-Behcet's disease: In special reference to MRI, SPECT and neuropathological findings","A case of neuro-Behcet's disease with dementia and personality changes is described with magnetic resonance imaging (MRI), single photon emission tomography (SPECT) and neuropathological findings. MRI disclosed high signal areas in the cerebral white matter and the brain stem. SPECT showed a marked reduction of blood flow in the frontal cortex. Neuropathologically, multifocal necrotizing lesions with perivascular lymphocytic infiltration and glial proliferation were detected mainly in the brain stem, namely the midbrain and the pons. From these findings, it is suggested that mental disorders of neuro-Behcet's disease are related to the secondary dysfunction of the frontal cortex due to the damage of the subcortical structures, mainly the brain stem.",,"Arai, T.;Mizukami, K.;Sasaki, M.;Tanaka, Y.;Shiraishi, H.;Horiguchi, H.;Ogata, T.",1994,1994,,0,
5595,Pitfalls of voxel-based amyloid PET analyses for diagnosis of Alzheimer's disease: artifacts due to non-specific uptake in the white matter and the skull,"Two methods are commonly used in brain image voxel-based analyses widely used for dementia work-ups: 3-dimensional stereotactic surface projections (3D-SSP) and statistical parametric mapping (SPM). The methods calculate the Z-scores of the cortical voxels that represent the significance of differences compared to a database of brain images with normal findings, and visualize them as surface brain maps. The methods are considered useful in amyloid positron emission tomography (PET) analyses to detect small amounts of amyloid-beta deposits in early-stage Alzheimer's disease (AD), but are not fully validated. We analyzed the (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227) amyloid PET imaging of 56 subjects (20 individuals with mild cognitive impairment [MCI], 19 AD patients, and 17 non-demented [ND] volunteers) with 3D-SSP and the easy Z-score imaging system (eZIS) that is an SPM-based method. To clarify these methods' limitations, we visually compared Z-score maps output from the two methods and investigated the causes of discrepancies between them. Discrepancies were found in 27 subjects (9 MCI, 13 AD, and 5 ND). Relatively high white matter uptake was considered to cause higher Z-scores on 3D-SSP in 4 subjects (1 MCI and 3 ND). Meanwhile, in 17 subjects (6 MCI, 9 AD, and 2 ND), Z-score overestimation on eZIS corresponded with high skull uptake and disappeared after removing the skull uptake (""scalping""). Our results suggest that non-specific uptakes in the white matter and skull account for errors in voxel-based amyloid PET analyses. Thus, diagnoses based on 3D-SSP data require checking white matter uptake, and ""scalping"" is recommended before eZIS analysis.",Aged;Alzheimer Disease/pathology/ radionuclide imaging;Amyloid;Artifacts;Benzoxazoles;Dementia/radionuclide imaging;Demography;Female;Humans;Male;Mild Cognitive Impairment/radionuclide imaging;Positron-Emission Tomography;Skull/ radionuclide imaging;Thiazoles;White Matter/pathology/ radionuclide imaging,"Arai, A.;Kaneta, T.;Okamura, N.;Tashiro, M.;Iwata, R.;Takanami, K.;Fukuda, H.;Takahashi, S.;Yanai, K.;Kudo, Y.;Arai, H.",2014,,,0,
5596,Combined effect of cerebral hypoperfusion and white matter lesions on executive functioning - The SMART-MR study,"Background/Aims: It has been hypothesized that cerebral hypoperfusion may contribute to cognitive deterioration. Patients with white matter lesions (WML) may be more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between CBF and cognitive performance and whether WML modified this relation. Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57 ± 10 years, 77% male). Total CBF was measured with magnetic resonance angiography in the internal carotid arteries and basilar artery, and was expressed per 100 ml brain volume. Neuropsychological tests assessing executive functioning and memory were performed and composite scores were calculated. We used linear regression analyses, adjusted for age, sex, education and intelligence, to investigate the association between CBF and cognitive performance. Results: We found that WML modified the association between CBF and executive functioning (p for interaction <0.001); the association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML. Lower CBF was not associated with worse memory. Conclusion: Our results suggest that a combination of lower CBF and WML may impair executive functioning but not memory. Copyright © 2010 S. Karger AG, Basel.",adult;aged;article;autoregulation;basilar artery;brain blood flow;brain circulation;brain damage;cerebral artery disease;cognition;cognitive defect;controlled study;disease association;disease course;female;human;intelligence;internal carotid artery;magnetic resonance angiography;major clinical study;male;memory;mental function;neuropsychological test;priority journal;white matter,"Appelman, A. P. A.;Van Der Graaf, Y.;Vincken, K. L.;Mali, W. P. T. M.;Geerlings, M. I.",2010,,,0,
5597,"Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors","BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are frequently characterized as markers of cerebrovascular disease, whereas medial temporal atrophy (MTA) is a recognized marker of Alzheimer disease (AD). Our purpose was to test the reliability of a visual rating system (VRS) in evaluating WMHs and MTA and in distinguishing healthy from cognitively impaired subjects. MATERIALS AND METHODS: Subjects (n = 192) enrolled in the Florida Alzheimer's Disease Research Center were diagnosed with no cognitive impairment, nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), or probable AD. The severity of WMHs was assessed on T2-weighted fluid-attenuated inversion recovery axial MR images, and the severity of MTA was evaluated on 1.5-mm-thick coronal MR images by using a computer-based visual rating system. Cardiovascular risk factor scores were calculated as the sum of 10 independent cardiovascular risk factors. RESULTS: WMH and MTA scores were greater in subjects with probable AD, relative to those with no cognitive impairment and na-MCI. MTA scores differentiated subjects with a-MCI from those with no cognitive impairment and na-MCI. The total WMH score was significantly related to MTA (r = 0.39; P < .001) but not to cardiovascular risk factor scores (r = 0.07; P = not significant). The overall correct classification rate of probable AD versus no cognitive impairment by using MTA scores was 81.8%, improving to 86.5% when combined with WMH scores. CONCLUSIONS: Both MTA and WMH scores distinguished subjects with no cognitive impairment and probable AD. Combining MTA and WMH scores improved the correct classification rate, whereas WMH scores were significantly related to MTA scores, but not to cardiovascular risk factor scores. This finding suggests that among subjects with a-MCI and probable AD, WMHs on MR images are primarily associated with neurodegenerative disease.","Aged;Aged, 80 and over;Alzheimer Disease/ epidemiology/ pathology;Cardiovascular Diseases/ epidemiology;Cognition;Female;Humans;Logistic Models;Magnetic Resonance Imaging/standards/ statistics & numerical data;Male;Nerve Fibers, Myelinated/ pathology;Observer Variation;Reproducibility of Results;Risk Factors;Severity of Illness Index;Temporal Lobe/ pathology","Appel, J.;Potter, E.;Bhatia, N.;Shen, Q.;Zhao, W.;Greig, M. T.;Raj, A.;Barker, W. W.;Potter, H.;Schofield, E.;Wu, Y.;Loewenstein, D. A.;Duara, R.",2009,Nov,10.3174/ajnr.A1693,0,
5598,Focal cortical subarachnoid hemorrhage revealed by recurrent paresthesias: a clinico-radiological syndrome strongly associated with cerebral amyloid angiopathy,"BACKGROUND: Focal subarachnoid hemorrhage (SAH) is often revealed by transient and recurrent focal neurological episodes. This cause is important to identify because it carries a high risk of intracerebral hemorrhage (ICH). We report the clinical, imaging and prognostic data of 17 patients with focal SAH revealed by short episodes of paresthesias mimicking transient ischemic attacks. METHODS: The medical records and imaging data of patients with focal acute SAH at the cerebral convexity and at least one episode of focal paresthesia having attended the Neurology Department of Caen University Hospital in the last 10 years were retrospectively reviewed. Hemorrhagic lesions, ischemic lesions, cerebral microbleeds (CMBs), superficial siderosis, white matter changes (leukoaraiosis) and modified Boston criteria for cerebral amyloid angiopathy (CAA) were assessed. All patients or relatives were contacted after a median delay of 16 months in order to seek for new events (death, stroke, recurrent focal symptoms, ICH and dementia) that occurred since hospital discharge. RESULTS: Seventeen patients (12 men) aged 69-96 years were identified. All but 1 had multiple, repeated, stereotyped and brief attacks of paresthesias, associated in some of them with motor and/or speech difficulties, but only 1 had a headache. SAHs were seen on CT scans in 15/17 patients and on T2* gradient-echo magnetic resonance imaging (MRI) in all patients. They were multiple SAHs in 14/17 patients, including at least 1 SAH in the central or pre- or postcentral sulcus contralateral to the symptoms in all patients. Five patients had punctate cortical hyperintensities on diffusion-weighted MRI. Eleven patients had CMBs, and 4 of them had more than 5 CMBs. Seven patients met the modified Boston criteria for probable and 10 for possible CAA. At follow-up, 5 patients had a subsequent ICH, 4 of whom had received antithrombotic treatments. Five patients died (1 from ICH). Six patients developed dementia. CONCLUSION: The combination of transient, repeated and stereotyped attacks of unilateral paresthesias with a contralateral sulcal SAH seems to preferentially occur in elderly people and is often indicative of CAA.","Aged;Aged, 80 and over;Cerebral Amyloid Angiopathy/ complications/pathology;Female;Humans;Ischemic Attack, Transient/ complications;Magnetic Resonance Imaging/methods;Male;Paresthesia/ complications/pathology;Retrospective Studies;Secondary Prevention;Subarachnoid Hemorrhage/ complications/pathology;Tomography, X-Ray Computed/methods","Apoil, M.;Cogez, J.;Dubuc, L.;Bataille, M.;de la Sayette, V.;Touze, E.;Viader, F.",2013,,10.1159/000353676,0,
5599,Association of descending thoracic aortic plaque with brain atrophy and white matter hyperintensities: The Framingham Heart Study,"BACKGROUND AND AIMS: Aortic atherosclerosis is an aggregate marker of vascular risk factor exposure and has been associated with intracranial atherosclerosis and stroke. We hypothesized that atherosclerosis of the descending aorta (DAo) could be a risk marker for brain aging and injury. METHODS: We evaluated 1527 participants (mean age 59.9 years, 53.5% women) in the Framingham Offspring cohort who underwent both aortic and brain MRI. Participants were free of clinical stroke, dementia, or other neurological illness at the time of axial MRI of the thoracic and abdominal DAo and subsequent brain MRI. We related the prevalence and burden of aortic plaque to total cerebral brain volume (TCBV) and white matter hyperintensity volume (WMHV). An additional analysis compared incidence of stroke or TIA in participants with and without DAo plaques. RESULTS: Presence of thoracic DAo plaque (8%) was associated with decreased TCBV in sex-pooled analysis (-0.77, SE 0.25, p = 0.002, equivalent to 4.5 years of aging) and with increased WMHV only in men (0.26, SE 0.12, p = 0.032, equivalent to 6.5 years aging). We observed similar associations of DAo plaque burden with TCBV and WMHV. There were 43 strokes and 11 TIAs in prospective follow-up (median 7 years). Presence of DAo plaque was not associated with subsequent stroke or TIA. CONCLUSIONS: In this cross-sectional community-based study, we found DAo plaque is associated with accelerated brain aging. These data underscore the potential implications of incidentally identified subclinical aortic atherosclerosis and question whether targeted intervention in these high risk individuals can modulate cognitive decline.",Aorta;Atherosclerosis;Brain;Cerebrovascular disorders;Magnetic resonance imaging;Neuroimaging;White matter,"Aparicio, H. J.;Petrea, R. E.;Massaro, J. M.;Manning, W. J.;Oyama-Manabe, N.;Beiser, A. S.;Kase, C. S.;D'Agostino, R. B.;Wolf, P. A.;Vasan, R. S.;DeCarli, C.;O'Donnell, C. J.;Seshadri, S.",2017,Oct,,0,
5600,Dramatic but temporary improvements in a case of CNS intravascular malignant lymphomatosis,"A 54-year-old man with a past history of gastric malignant lymphoma treated by the total gastrectomy and the chemotherapy, developed bilateral sudden deafness one year later. Two years after the gastrectomy he became abruptly paraplegic with sensory impairments of the lower extremities and neurogenic bladder. Serum LDH and soluble IL-2 receptor were high in titers (552 U/l and 1,090U/l, normal range 145-519). Although the imaging studies of the spinal cord were negative, the myelopathic symptoms resolved dramatically after a course of pulse dose methylprednisolone therapy. However, he soon developed an abnormal behavior and mental deterioration in 3 weeks. The MRIs of the brain revealed abnormal signals compatible with multiple cerebral infarctions. As intravascular malignant lymphomatosis (IML) was suspected because of the laboratory and MRI findings, biopsies of the skin, the bone marrow, the muscle and the lymph node were carried out, without evidence of lymphoma. The brain biopsy ultimately confirmed the presence of IML. The patient remarkably responded to biweekly CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in terms of regaining the mental alertness and improved hearing. However, the CHOP therapy was prematurely interrupted prior to completion because of infective arthritis. The relapse soon ensued, and he died 6 months after admission. This case was of interest because a solid gastric lymphoma appears to have transformed into the form of intravascular lymphomatosis without mass formations or leukemic changes. Although the neurological symptoms in association with IML are thought to be the results of ischemic events, this case illustrates a remarkable reversibility of the symptoms. This implies that the cerebral symptoms are not necessarily the results of typical ischemic infarction, but due to relative ischemia because of chiefly capillary-venous occlusion by lymphoma cells. The majority of the symptoms is thus attributable to the functional impairment. Therefore, the therapeutic intervention may dramatically improve the symptoms due to IML.",,"Aoyama, M.;Aoki, T.;Matsuura, Y.;Yamanoi, T.;Watanabe, A.;Saitou, N.;Honma, M.;Ishikawa, T.;Kodama, N.;Yamamoto, T.",2003,1,,0,
5601,Magnetic resonance diffusion tractography in the brain - Its application and limitation,"Diffusion tractography of magnetic resonance imaging (MRI), such as diffusion tensor tractography, allows us to visualize white matter tracts in vivo and to study white matter integrity quantitatively. Virtual dissection of the living human brain can be performed in the first time. We developed tracking software, dTV and VOLUME-ONE, in 2001, as a freeware (http://www.ut-radiology. umin.jp/people/masutani/dTV. htm), and we used it to visualize eloquent white matter bundles with relationship to brain tumors, cerebral infarctions and other lesions. We also used it for quantitative measurement of the specific tracts segmented by diffusion tensor tractography (tract-specific analysis) to reveal abnormalities in so-called normal appearing white matter. Three dimensional visualization of the white matter fibers such as corticospinal (pyramidal) tract, optic radiation and arcuate fasciculus with relationship to brain tumors such as gliomas was extremely helpful for preoperative evaluation and intraoperative navigation. We correlated tracking with intraoperative electric fiber stimulation to validate fiber tracking. In patients with small lacunar infarctions near the corticospinal tracts, relationship between the tract and fresh infarction correlated well with final (2 weeks-later) motor function. Quantitative measurement of the tract is a very sensitive tool. We analyzed the corticospinal and corticobulbar tracts in patients with amyotrophic lateral sclerosis (ALS). Changes of the diffusion parameters (fractional anisotropy and ADC) of the tracts were observed not only between normal controls but also between subtypes of ALS (limb- and bulbar-onset). Tract- specific analysis can also apply for the limbic-related tracts such as fornix, cingulum, uncinate fasciculus and etc. We observed differences in some of the fibers in neurocognitive/psychiatric patients such as schizophrenia and Alzheimer disease. Using fiber tracking, we can now develop white matter mapping. We visualized components of the pyramidal tract (fibers from foot, hand, face motor areas separately) and made a probabilistic map. Diffusion tractography is a unique tool to visualize and segment the white matter pathways and one can evaluate the segmented tract quantitatively. Importance of this tool will become more significant in clinical and neuroscience fields in the future.",,"Aoki, S.;Masutani, Y.;Abe, O.",2007,May,,0,
5602,A presenilin-1 mutation in a Japanese family with Alzheimer's disease and distinctive abnormalities on cranial MRI,Some patients with familial Alzheimer's disease (FAD) have mutations in the presenilin-1 (PS-1) gene on chromosome 14. We report a Japanese family with AD an Ala285Val substitution in exon 8 of the PS-1 gene. FAD in this family was characterized by relatively late onset (mean age 50 years) absence of myoclonus seizures or paratonia. Levels of tau were markedly elevated in CSF whereas CSF levels of amyloid protein were normal. MRI of the cranium showed marked linear signal abnormalities within white matter in the parieto- occipital lobes consistent with cortical amyloid angiopathy of the type encountered in patients with the PS-1 gene mutation.,amyloid precursor protein;adult;allele;Alzheimer disease;article;brain mapping;case report;chromosome 14q;familial disease;female;gene location;gene mutation;human;Japan;neurofibrillary tangle;nuclear magnetic resonance imaging;priority journal,"Aoki, M.;Abe, K.;Oda, N.;Ikeda, M.;Tsuda, T.;Kanai, M.;Shoji, M.;St. George-Hyslop, P. H.;Itoyama, Y.",1997,,,0,
5603,Methotrexate leukoencephalopathy presenting as Klüver-Bucy syndrome and uncinate seizures,"Methotrexate causes several biochemical changes that impact the nervous system. The neurotoxicity usually affects the cerebral white matter, causing a leukoencephalopathy that can be chronic and progressive with cognitive decline. A 15-year-old male developed olfactory seizures and behavioral abnormalities (hypersexuality, placidity, and memory disturbances) compatible with partial Klüver-Bucy syndrome after treatment for central nervous system leukemia with intraventricular methotrexate. A magnetic resonance imaging study revealed evidence of white matter disease affecting both temporal lobes. A brain biopsy revealed a necrotizing encephalopathy compatible with methotrexate-related white matter injury. It may be prudent to verify normal cerebrospinal fluid dynamics before the administration of intraventricular methotrexate in children with a history of central nervous system leukemia. © 2002 by Elsevier Science Inc. All rights reserved.",,"Antunes, N. L.;Souweidane, M. M.;Lis, E.;Rosenblum, M. K.;Steinherz, P. G.",2002,2002,,0,
5604,Hippocampal Pathway Plasticity Is Associated with the Ability to Form Novel Memories in Older Adults,"White matter deterioration in the aging human brain contributes to cognitive decline. The fornix as main efferent hippocampal pathway is one of the tracts most strongly associated with age-related memory impairment. Its deterioration may predict conversion to Alzheimer's dementia and its precursors. However, the associations between the ability to form novel memories, fornix microstructure and plasticity in response to training have never been tested. In the present study, 25 healthy older adults (15 women; mean age (SD): 69 (6) years) underwent an object-location training on three consecutive days. Behavioral outcome measures comprised recall performance on the training days, and on 1-day and 1-month follow up assessments. MRI at 3 Tesla was assessed before and after training. Fornix microstructure was determined by fractional anisotropy and mean diffusivity (MD) values from diffusion tensor imaging (DTI). In addition, hippocampal volumes were extracted from high-resolution images; individual hippocampal masks were further aligned to DTI images to determine hippocampal microstructure. Using linear mixed model analysis, we found that the change in fornix FA from pre- to post-training assessment was significantly associated with training success. Neither baseline fornix microstructure nor hippocampal microstructure or volume changes were significantly associated with performance. Further, models including control task performance (auditory verbal learning) and control white matter tract microstructure (uncinate fasciculus and parahippocampal cingulum) did not yield significant associations. Our results confirm that hippocampal pathways respond to short-term cognitive training, and extend previous findings by demonstrating that the magnitude of training-induced structural changes is associated with behavioral success in older adults. This suggests that the amount of fornix plasticity may not only be behaviorally relevant, but also a potential sensitive biomarker for the success of training interventions aimed at improving memory formation in older adults, a hypothesis to be evaluated in future studies.",,"Antonenko, D.;Kulzow, N.;Cesarz, M. E.;Schindler, K.;Grittner, U.;Floel, A.",2016,,10.3389/fnagi.2016.00061,0,
5605,Brain pathway differences between Parkinson’s disease patients with and without REM sleep behavior disorder,"Purpose: REM (rapid eye movement) sleep behavior disorder (RBD) is characterized by increased muscle tone and violent limb movements and is a usual symptom of the early stages of Parkinson’s disease (PD). PD patients with RBD represent faster motor and cognitive dysfunction progression. However, there are limited studies on possible structural brain changes underpinning this disorder. Methods: Diffusion magnetic resonance imaging (DMRI) was used to assess whether microstructural abnormalities in the brain of 23 RBD positive PD are detectable compared to 31 RBD negative PD. DMRI scans were analyzed without a prior hypothesis. Diffusion MRI connectometry was used to carry out group analysis between age and gender matched PD patients with and without RBD. Diffusion MRI connectometry is based on spin distribution function (SDF) which quantifies the density of diffusing water and is more sensitive to psychological differences between groups. Results: Patients with RBD positive showed microstructural white matter changes in the left and right cingulum, inferior front occipital fasciculus (IFOF), bilateral corticospinal tracts (CST), and middle cerebellar peduncles (MCPs), compared to patients without RBD. Conclusions: White matter alterations in the cingulum, IFOF regions, and corpus callosum might explain faster cognitive deterioration in PD patients with RBD, in terms of visual recognition and visuospatial dysfunction and executive function. Disturbed brain structural tissue markers in CST in PD + RBD patients, could be justified in the light of faster motor progression in these patients.",dopamine transporter;adult;anisotropy;article;cingulum (brain);cognition;connectome;controlled study;corpus callosum;depth perception;diffusion tensor imaging;diffusion weighted imaging;Epworth sleepiness scale;executive function;female;functional connectivity;functional neuroimaging;Geriatric Depression Scale;human;major clinical study;male;mental deterioration;middle aged;middle cerebellar peduncle;Montreal cognitive assessment;occipitofrontal fasciculus;parasomnia;Parkinson disease;priority journal;pyramidal tract;REM sleep;somnolence;visual memory;white matter,"Ansari, M.;Rahmani, F.;Dolatshahi, M.;Pooyan, A.;Aarabi, M. H.",2017,,10.1007/s11325-016-1435-8,0,
5606,"Neuropsychiatric Symptoms in Alzheimer Disease, Vascular Dementia, and Mixed Dementia","BACKGROUND/AIMS: Neuropsychiatric symptoms (NPS) are common in Alzheimer disease (AD) and vascular dementia (VaD), and are distressful to patients and caregivers. NPS are likely related to the underlying pathology. Previous studies suggest that frontal lobe lesions and vascular changes such as white matter hyperintensities (WMH) have a significant association with specific NPS. The current study aimed to compare NPS in patients with AD, VaD, and mixed AD/VaD, and to evaluate the differences in the prevalence of NPS in relation to frontal WMH volume. METHODS: In total, 180 patients with NPS and MRI data (92 probable AD, 51%; 34 probable VaD, 19%; and 54 probable mixed AD/VaD, 30%) were included in the study. Regression analyses were performed to determine the relationships between NPS prevalence and diagnosis, and between NPS and frontal WMH. RESULTS: VaD patients had significantly more agitation (p < 0.05; 40 vs. 14%) and sleep disturbances (p < 0.05; 57 vs. 32%) than AD patients, and significantly more depression (p < 0.05; 48 vs. 20%) and aberrant motor behaviors (p < 0.05; 31 vs. 13%) than mixed AD/VaD patients. AD patients with delusions had significantly greater right frontal WMH volumes than those without (p < 0.05; delusions 1/0 = 314.8/112.6 mm3). CONCLUSION: Differences in NPS prevalence are likely related to the underlying pathology and warrant further study as they have implications for treatment.",,"Anor, C. J.;O'Connor, S.;Saund, A.;Tang-Wai, D. F.;Keren, R.;Tartaglia, M. C.",2017,Mar 01,,0,
5607,"[Public title] Aspirin for the prevention of cognitive decline in the Elderly: a Neuro-Vascular Imaging Study (ENVIS-ion), a sub-study of ASPirin in Reducing Events in the Elderly (ASPREE); [Official title] A multi-centre, randomised, double-blind, placebo controlled trial of the effects of 100mg enteric-coated aspirin on rate of increase of magnetic resonance imaging(MRI)-based white matter hyperintensity (WMH) and silent brain infarction (SBI)",,,Anon,2008,,,0,
5608,Slow gait in MCI is associated with ventricular enlargement: results from the Gait and Brain Study,"Slow gait is ubiquitous among older adults and predicts cognitive decline and progression to dementia. Age-related structural brain changes could be responsible for abnormal gait. The purpose of this study was to determine whether brain lateral ventricle volume, a measure of brain atrophy, was associated with gait velocity among older adults with mild cognitive impairment (MCI), while considering the effects of age and brain vascular burden. Twenty community-dwellers with MCI, free of hydrocephalus, aged 76 years (69/80) [median (25th/75th percentile)] (35 % female) from the 'Gait and Brain Study' were included in this analysis. Quantitative gait performance was measured while steady-state walking at self-selected pace with a 6-m electronic portable walkway (GAITRite). Brain ventricle volume was quantified using semi-automated software from three-dimensional T1-weighted magnetic resonance imaging. Age, white matter hyperintensity burden and Mini-Mental State Examination score were used as potential confounders. Median gait velocity was 118.7 cm/s (104.4/131.3). Median brain ventricle volume was 39.9 mL (30.0/46.6) with the left ventricle being slightly larger than the right (P = 0.052). Brain ventricle volume was inversely associated with gait velocity (adjusted beta = -0.63, P = 0.046). Volume of both the ventricular main bodies and the temporal horns correlated inversely with gait velocity (respectively, P = 0.009, P = 0.008). Left ventricle volume correlated with decreased gait velocity (P = 0.002) while right ventricle did not (P = 0.068). Slower gait velocity was associated with larger brain ventricle volume in our sample of people with MCI independent of age, cerebrovascular burden and cognitive worsening. This result may help elucidate the trajectories of cognitive and gait declines in people with MCI.","Aged;Aged, 80 and over;Brain/ pathology;Female;Gait/ physiology;Gait Disorders, Neurologic/ etiology/ pathology;Humans;Imaging, Three-Dimensional;Lateral Ventricles/ pathology;Magnetic Resonance Imaging;Male;Mental Status Schedule;Middle Aged;Mild Cognitive Impairment/ complications","Annweiler, C.;Beauchet, O.;Bartha, R.;Montero-Odasso, M.",2013,Jul,10.1007/s00702-012-0926-4,0,
5609,The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review,"Divry van Bogaert Syndrome (DBS) is a familial juvenile-onset disorder characterized by livedo racemosa, white matter disease, dementia, epilepsy and angiographic finding of ""cerebral angiomatosis"". A similar syndrome including livedo racemosa and cerebrovascular disease, often associated with anticardiolipin antibodies, has been described as Sneddon Syndrome (SS) highlighting the question whether these two conditions have to be considered different entities or indeed different features of a unique syndrome. Herein, we report the clinical, neuroradiological, histopathological findings and follow up of three cases diagnosed as Divry-van Bogaert Syndrome, including an updated review of literature of both DBS and SS cases. Our findings support the assumption that DBS and SS are different disease entities. DBS is characterized by the typical angiographic feature of angiomatosis, a hereditary trait and a juvenile onset of cognitive impairment and leukoaraiosis, whereas SS has less severe manifestations of cerebrovascular disease associated with livedo racemosa but without the characteristic cerebral angiography. The report of our cases and the literature review underline the necessity of a detailed work-up and the collection of larger series to better clarify the DBS and SS phenotype and course.",acetylsalicylic acid;anticonvulsive agent;antithrombocytic agent;azathioprine;beta adrenergic receptor blocking agent;clopidogrel;cyclophosphamide;dipeptidyl carboxypeptidase inhibitor;Notch3 receptor;steroid;adult;article;case report;cerebrovascular disease;cognitive defect;disease association;Divry van Bogaert Syndrome;drug substitution;drug withdrawal;familial disease;female;follow up;hemangiomatosis;histopathology;human;hypertension;leukoaraiosis;male;neuroimaging;nuclear magnetic resonance imaging;priority journal;skin biopsy;Sneddon syndrome,"Anna, B.;Michela, M.;Elisa, C.;Gloria, B.;Peter, B.;Michele, H.;Stefania, S.;Valeria, F.;Hannes, N.;Giuseppe, F.;Mario, S.;Franco, T.;Mariarita, C.;Battista, B. G.;Laura, P.;Luigi, C.;Agostino, P. E.;Markus, K.",2016,,,0,
5610,Age-dependent neurologic manifestations of HIV infection in childhood,"Although the neurologic complications of HIV- 1 infection during the first two years of life have been defined, the neurologic features in older children are not so well described. The present report is focused on the age-dependent neurologic presentation of HIV-1 infection. Sixty-two vertically HIV-1 infected children underwent detailed serial evaluations: neurologic assessment, neuropsychological tests, neuroimaging studies, and cerebrospinal fluid analysis. Neurologic involvement was found in 30 patients (48.3%). This population was divided into two groups, exhibiting progressive (83.3%) or nonprogressive (16.6%) neurologic signs and symptoms. In the first group of patients, progressive encephalopathy was distinguished from spastic paraparesis, possibly due to spinal cord involvement. The second group, represented by long-term survivors, requires clinical monitoring due to the possible prognostic value of acquired but presently nonprogressive signs of brain involvement. In contrast with the stereotyped features of the early form of progressive encephalopathy, the late form showed a polymorphic picture, with age-dependent neurologic manifestations. Multifocal white matter alterations and cerebral calcifications (sometimes with delayed onset and progression) were the prominent imaging findings. A correlation between cerebrospinal fluid HIV RNA levels, suggestive of viral replication within the central nervous system, and progressive neurological disease were also found.","AIDS Dementia Complex/ diagnosis;Age Factors;Brain/virology;Brain Neoplasms/diagnosis;Child;Child, Preschool;Diagnosis, Differential;Disease Progression;Female;Hiv-1;Humans;Male;Paraparesis, Spastic/ diagnosis/virology;RNA, Viral/cerebrospinal fluid;Spinal Cord Diseases/diagnosis/virology;Tomography, X-Ray Computed;Viral Load","Angelini, L.;Zibordi, F.;Triulzi, F.;Cinque, P.;Giudici, B.;Pinzani, R.;Plebani, A.",2000,Jun,,0,
5611,Angiotropic lymphoma presenting with subacute dementia: Treatment with combination chemotherapy (CHOP) based on antemortem diagnosis - A case report,"We report a 64-year-old male with angiotropic lymphoma. He developed subacute dementia with right hemiparesis. Laboratory abnormalities included elevated serum lactic dehydrogenase (LDH) (715 U/l), erythrocyte sedimentation rate (38 mm/hr) and CSF protein (90 mg/dl). Precontrast MR imaging of the brain demonstrated lesions involving the left internal capsule, subcortical white matter in the right frontal lobe and splenium within the atrophic corpus callosum. A brain biopsy revealed intravascular lymphoid cells, strongly suggestive of angiotropic lymphoma. By combination chemotherapy (CHOP), serum LDH and CSF protein normalized though the patient remained demented. He died of bronchopneumonia about 2 years and 5 months after the onset. Coronal sections of the brain showed infarct in the left internal capsule as well as markedly thin corpus callosum with necrotic lesions involving both the genu and splenium. Microscopic examination showed many small vessels occluded by lymphoma cells (B-lymphocyte) predominantly in the corpus callosum, cerebral white matter, thalamus, midbrain, medulla oblongata, thoracic and lumbar segments of the spinal cord. By combination chemotherapy, our patient survived longer than most of previous patients with angiotropic lymphoma. An early diagnosis and subsequent combination chemotherapy may improve neurological manifestations, and make possible longer survival in angiotropic lymphoma.",,"Anegawa, T.;Hara, K.;Kusaka, H.;Fujiyoshi, K.;Matsuda, M.",1993,1993,,0,
5612,Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls,"Background: Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. Objective: To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. Materials and methods: A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Results: Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Conclusion: Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls.",article;brain size;child;clinical article;controlled study;corpus callosum;corpus callosum thickness;cross-sectional study;female;HIV associated dementia;human;Human immunodeficiency virus;Human immunodeficiency virus infected patient;Human immunodeficiency virus infection;male;nervous system parameters;neuroimaging;nuclear magnetic resonance imaging;pilot study;preschool child;priority journal;retrospective study;white matter,"Andronikou, S.;Ackermann, C.;Laughton, B.;Cotton, M.;Tomazos, N.;Spottiswoode, B.;Mauff, K.;Pettifor, J. M.",2015,,,0,
5613,Disruption of Large-Scale Brain Systems in Advanced Aging,"Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition. © 2007 Elsevier Inc. All rights reserved.",,"Andrews-Hanna, J. R.;Snyder, A. Z.;Vincent, J. L.;Lustig, C.;Head, D.;Raichle Marcus, E.;Buckner, R. L.",2007,6,,0,
5614,Viral encephalitis,"Patients with viral infections of the central nervous system are encountered daily, but it is often difficult to establish a correct differential diagnosis. This paper attempts to 'reorganize' our knowledge of such infections. Our starting point was virology, defining the different viruses according to the latest classifications, distinguishing RNA viruses from DNA viruses, assessing capsid shape and dividing each family into genera and species of interest. We then determined the pathophysiology: from initial viraemia we considered the mechanisms of CNS penetration and the pathological changes which ensue. The different species of viruses were found to behave in a broadly similar fashion, accounting for the often very similar radiological findings which make differential diagnosis arduous even for the expert. Lastly, we studied the different forms of slow and acute encephalitis aiming to separate crucial information from useful findings which together with clinical presentation will aid diagnosis. Among the acute forms of encephalitis, the main group comprises herpes encephalitis caused by herpes simplex virus types 1 and 2, cytomegalovirus and varicella-zoster virus. HS1 is usually responsible for severe necrotising meningo-encephalitis; type 2 often presents symmetrical malacic areas in the white matter with little involvement of the grey matter. Cytomegalovirus, which is dangerous mainly to the fetus and neonate, is responsible for dystrophic calcifications and neuronal migration disorders, sometimes resuiting in lissencephaly; in immunodepressed patients, it causes atrophy and leukoencephalopathy without damage to the brain barrier. Varicella-zoster virus is responsible for transverse myelitis, asectic meningitis and meningo-encephalitis, often presenting a characteristic subtentorial location, sometimes complicated by patchy haemorrhagic lesions. The slow forms of encephalitis include subacute sclerosing panencephalitis caused by measles-like paramyxovirus which presents aspecific signs from neuronal degeneration to atrophy. HIV encephalitis causes atrophy and leucoencephalopathy without damage to the blood brain barrier. Progressive multifocal leucoencephalopathy caused by papavirus is characterized by involvement of the subcortical oligodendrocytes resulting in a leucoencephalopathy presenting a typical finger shape often in a subtentorial site.",CD4 antigen;contrast medium;agyria;article;aseptic meningitis;blood brain barrier;calcification;computer assisted tomography;Creutzfeldt Jakob disease;Cytomegalovirus;differential diagnosis;DNA virus;herpes simplex encephalitis;Herpes simplex virus;human;Human immunodeficiency virus infection;meningoencephalitis;myelitis;neuroradiology;nuclear magnetic resonance imaging;Paramyxoviridae;progressive multifocal leukoencephalopathy;RNA virus;subacute sclerosing panencephalitis;Varicella zoster virus;virus encephalitis,"Andreula, C. F.;Marano, G.;Kambas, I.",1997,,,0,
5615,Diverging Progression of Network Disruption and Atrophy in Alzheimer's Disease and Semantic Dementia,"The progression of cognitive deficits in Alzheimer's disease and semantic dementia is accompanied by grey matter atrophy and white matter deterioration. The impact of neuronal loss on the structural network connectivity in these dementia subtypes is, however, not well understood. In order to gain a more refined knowledge of the topological organization of white matter alterations in dementia, we used a network-based approach to analyze the brain's structural connectivity network. Diffusion-weighted and anatomical MRI images of groups with eighteen Alzheimer's disease and six semantic dementia patients, as well as twenty-one healthy controls were recorded to reconstruct individual connectivity networks. Additionally, voxel-based morphometry, using grey and white matter volume, served to relate atrophy to altered structural connectivity. The analyses showed that Alzheimer's disease is characterized by decreased connectivity strength in various cortical regions. An overlap with grey matter loss was found only in the inferior frontal and superior temporal areas. In semantic dementia, significantly reduced network strength was found in the temporal lobes, which converged with grey and white matter atrophy. Therefore, this study demonstrated that the structural disconnection in early Alzheimer's disease goes beyond grey matter atrophy and is independent of white matter volume loss, an observation that was not found in semantic dementia.",Alzheimer's disease;atrophy;diffusion magnetic resonance;frontotemporal dementia;structural connectivity,"Andreotti, J.;Dierks, T.;Wahlund, L. O.;Grieder, M.",2017,,,0,
5616,A novel heterozygous mutation in the NOTCH3 gene causing CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an identifiable cause of inherited stroke among young adults, characterised by diffuse leukoencephalopathy with prominent involvement of the temporal poles and external capsule. The disease is caused by mutations in the NOTCH3 gene encoding a NOTCH3 receptor protein. The clinical course is relentlessly progressive with early transient ischaemic attacks (TIA) or strokes, dementia and finally death in the mid-60s. We describe a 40-year-old patient with clinical features of CADASIL and a positive family history who was a carrier of a new mutation at the exon 4 of the NOTCH3 gene: C162R. Regardless of the distinctive clinical and neuroimaging features one of his siblings had been mistakenly diagnosed as suffering from multiple sclerosis (MS), suggesting that the disease can occasionally be misdiagnosed as MS.",gadolinium;hexamethylpropylene amine oxime technetium tc 99m;Notch3 receptor;adult;article;attention deficit disorder;brain damage;CADASIL;case report;caudate nucleus;cerebrospinal fluid analysis;death;dementia;diagnostic error;disease course;exon;family history;gene;gene mutation;hemisphere;human;hypothalamus periventricular nucleus;male;multiple sclerosis;neuroimaging;neuropsychological test;Notch3 receptor gene;nuclear magnetic resonance imaging;occipital lobe;sibling;single photon emission computer tomography;temporal lobe;transient ischemic attack;white matter,"Andreadou, E.;Papadimas, G.;Sfagos, C.",2008,,,0,
5617,Radiosynthesis of the candidate beta-amyloid radioligand (11)C AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys,"Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Abeta-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand. [(11)C]5 was prepared by a two-step radiosynthesis starting with the reaction of 5-(6-(tert-butyldimethylsilyloxy)benzo[d]thiazol-2-yl)pyridin-2-amine with [(11)C]methyl iodide followed by deprotection using water. Four brain PET measurements in two cynomolgus monkeys and one whole-body PET measurement were performed with [(11)C]5. There was a high and rapid brain uptake (2.2-3.4% of injected dose at 2 min). The distribution of brain radioactivity was fairly uniform, with early to late-brain concentration ratios (peak vs. 60 min) higher for [(11)C]5 than ratios previously reported for [(11)C]PIB (8.2 and 4.6, respectively). Based on the whole-body data, it was estimated that an effective dose in an adult male would be 6.2 muSv/MBq and thus would be safe from a radiation point of view for multiple scans within the same year. [(11)C]5 shows binding characteristics, suggesting low levels of white-matter retention, and may thus provide improved contrast when compared with currently used PET radioligands for visualization of Abeta-deposits. On the basis of the labeling chemistry and the results of the biological evaluation, we conclude that [(11)C]5 should be useful for routine clinical studies.","Aminopyridines/chemistry/ metabolism;Animals;Benzothiazoles/chemistry/ metabolism;Brain/anatomy & histology/ metabolism/ radionuclide imaging;Carbon Radioisotopes/chemistry/ metabolism;Chromatography, High Pressure Liquid/methods;Imaging, Three-Dimensional/methods;Macaca fascicularis/anatomy & histology/ metabolism;Mass Spectrometry;Positron-Emission Tomography;Radiochemistry/methods;Whole Body Imaging/methods","Andersson, J. D.;Varnas, K.;Cselenyi, Z.;Gulyas, B.;Wensbo, D.;Finnema, S. J.;Swahn, B. M.;Svensson, S.;Nyberg, S.;Farde, L.;Halldin, C.",2010,Oct,10.1002/syn.20782,0,
5618,Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke,"BACKGROUND AND PURPOSE: Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort. METHODS: We followed 3374 stroke- and dementia-free individuals (mean age, 59.0+/-9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8+/-3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing approximately 4.0+/-1.7 years after the sixth examination. RESULTS: After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (beta coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (beta coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (beta for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. CONCLUSIONS: Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury.","Aged;Biomarkers/blood;Brain/ pathology/physiopathology;Cerebrovascular Trauma/ blood;Cognition Disorders/ blood;Cross-Sectional Studies;Female;Growth Differentiation Factor 15/ blood;Humans;Ischemic Attack, Transient/ blood;Longitudinal Studies;Magnetic Resonance Imaging;Male;Middle Aged;Receptors, Cell Surface/ blood;Stroke/ blood","Andersson, C.;Preis, S. R.;Beiser, A.;DeCarli, C.;Wollert, K. C.;Wang, T. J.;Januzzi, J. L., Jr.;Vasan, R. S.;Seshadri, S.",2015,Sep,10.1161/strokeaha.115.009026,0,
5619,Central nervous system imaging findings of hemophagocytic syndrome,"We present a rare case of intracranial involvement in hemophagocytic lymphohistiocytosis (HLH) in an adult patient. MRI features in HLH may mimic those of other neoplastic, infectious, or inflammatory disorders. Key imaging findings correlate to central nervous system inflammation and include diffuse leptomeningeal enhancement, white matter changes with variable enhancement, hemorrhage, and restricted diffusion. Recognition of the imaging characteristic in correlation with clinical presentation, laboratory values, and biopsy findings is essential for making a correct diagnosis.",,"Anderson, T. L.;Carr, C. M.;Kaufmann, T. J.",2015,1,,0,
5620,The effect of advanced old age on the neurone content of the cerebral cortex. Observations with an automatic image analyser point counting method,"The effect of advanced old age on the nerve cell content of the cerebral cortex was examined in 19 non-demented persons aged 69-95 years, using a Quantimet 720 image analysing computer to make area proportion measurements. Neurone loss around 1.0% per annum was found both in the neocortex and in the medial hippocampus. There was also significant shrinkage of neurones in the hippocampus. Macroscopic measurements of the cerebral hemispheres by means of point-counting morphometry showed a corresponding reduction in the volume of white matter amounting to about 0.8% per annum, but only a minor change in the cortex volume. This finding is consistent with the occurrence of dendritic growth of surviving neocortical neurones. By contrast, there appears to be no compensatory dendritic proliferation in the medial hippocampus since tissue atrophy was commensurate with cell loss in this region.",Aged;Aging;Cell Count;Cerebral Cortex/ cytology;Female;Gyrus Cinguli/cytology;Hippocampus/cytology;Humans;Male;Neurofibrils/ultrastructure;Neurons/cytology,"Anderson, J. M.;Hubbard, B. M.;Coghill, G. R.;Slidders, W.",1983,Feb,,0,
5621,Effects of bilingualism on white matter integrity in older adults,"Bilingualism can delay the onset of dementia symptoms and has thus been characterized as a mechanism for cognitive or brain reserve, although the origin of this reserve is unknown. Studies with young adults generally show that bilingualism is associated with a strengthening of white matter, but there is conflicting evidence for how bilingualism affects white matter in older age. Given that bilingualism has been shown to help stave off the symptoms of dementia by up to four years, it is crucial that we clarify the mechanism underlying this reserve. The current study uses diffusion tensor imaging (DTI) to compare monolinguals and bilinguals while carefully controlling for potential confounds (e.g., I.Q., MMSE, and demographic variables). We show that group differences in Fractional Anisotropy (FA) and Radial Diffusivity (RD) arise from multivariable interactions not adequately controlled for by sequential bivariate testing. After matching and statistically controlling for confounds, bilinguals still had greater axial diffusivity (AD) in the left superior longitudinal fasciculus than monolingual peers, supporting a neural reserve account for healthy older bilinguals.",Aging;Bilingualism;Dti;Propensity score matching;White matter,"Anderson, J. A. E.;Grundy, J. G.;De Frutos, J.;Barker, R. M.;Grady, C.;Bialystok, E.",2017,Nov 22,,0,
5622,Segmentation and Analysis of Corpus Callosum in Alzheimer MR Images using Total Variation Based Diffusion Filter and Level Set Method,"Alzheimers Disease (AD) is a common form of dementia that affects gray and white matter structures of brain. Manifestation of AD leads to cognitive deficits such as memory impairment problems, ability to think and difficulties in performing day to day activities. Although the etiology of this disease is unclear, imaging biomarkers are highly useful in the early diagnosis of AD. Magnetic resonance imaging is an indispensible non-invasive imaging modality that reflects both the geometry and pathology of the brain. Corpus Callosum (CC) is the largest white matter structure as well as the main inter-hemispheric fiber connection that undergoes regional alterations due to AD. Therefore, segmentation and feature extraction are predominantly essential to characterize the CC atrophy. In this work, an attempt has been made to segment CC using edge based level set method. Prior to segmentation, the images are pre-processed using Total Variation (TV) based diffusion filtering to enhance the edge information. Shape based geometric features are extracted from the segmented CC images to analyze the CC atrophy. Results show that the edge based level set method is able to segment CC in both the normal and AD images. TV based diffusion filtering has performed uniform region specific smoothing thereby preserving the texture and small scale details of the image. Consequently, the edge map of CC in both the normal and AD are apparently sharp and distinct with continuous boundaries. This facilitates the final contour to correctly segment CC from the nearby structures. The extracted geometric features such as area, perimeter and minor axis are found to have the percentage difference of 5.97%, 22.22% and 9.52% respectively in the demarcation of AD subjects. As callosal atrophy is significant in the diagnosis of AD, this study seems to be clinically useful.",,"Anandh, K. R.;Sujatha, C. M.;Ramakrishnan, S.",2015,,,0,
5623,On the diagnosis of CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic arteriopathy related to Notch3 mutations, is difficult to diagnosis. The goal of this study was to determine the value of clinical, immunohistochemical, and molecular techniques for the diagnosis of CADASIL. Clinical features and the immunohistochemical and molecular findings in 200 subjects with suspected CADASIL in whom 93 biopsies and 190 molecular studies are reported. Eighteen pathogenic mutations of the Notch3 gene, six of them previously unreported, were detected in 67 patients. The clinical features did not permit differentiation between CADASIL and CADASIL-like syndromes. The sensitivity and specificity of the skin biopsies was 97.7% and 56.5%, respectively, but increased to 100% and 81.5%, respectively, in cases with proven family history. In conclusion, a clinical diagnosis of CADASIL is difficult to determine and confirmatory techniques should be used judiciously.","Aged;Biopsy;Brain/*pathology;CADASIL/*diagnosis/genetics/pathology/physiopathology;Diagnosis, Differential;Female;Follow-Up Studies;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Male;Middle Aged;Mutation;Polymerase Chain Reaction;Receptors, Notch/*genetics/metabolism;Sensitivity and Specificity;Skin/*pathology;Spain/epidemiology;Surveys and Questionnaires","Ampuero, I.;Alegre-Abarrategui, J.;Rodal, I.;Espana, A.;Ros, R.;Sendon, J. L.;Galloway, E. G.;Cervello, A.;Caminero, A. B.;Zabala, A.;Erro, E.;Jarauta, F.;Morlan, L.;Lopez-Valdes, E.;Aladro, Y.;Seijo, M.;Rivas, G. G.;Munoz, D. G.;de Yebenes, J. G.",2009,,10.3233/jad-2009-1112,0,
5624,Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity,"PURPOSE: To evaluate the relationship between (a) pathologic levels of cerebrospinal fluid (CSF) total tau as an index of the intensity of ongoing neuronal degeneration and (b) longitudinal changes in white matter (WM) integrity in patients with mild cognitive impairment (MCI). MATERIALS AND METHODS: Participants gave written informed consent, and the Norwegian committee for medical research ethics approved the study. Thirty patients with MCI and nonpathologic CSF total tau levels, nine patients with MCI and pathologic CSF total tau levels, and 16 age-matched healthy control subjects underwent diffusion-tensor imaging at baseline and after a mean follow-up of 2.6 years +/- 0.54 (standard deviation), with range of 1.58-3.98 years. The effect of diagnosis (MCI vs no MCI) at baseline and CSF tau levels at fractional anisotropy (FA), mean diffusivity, radial diffusivity (D(R)), and axial diffusivity were tested with tract-based spatial statistics. Differences in WM integrity at baseline and follow-up and change over time were compared among patients with pathologic CSF total tau levels (MCI high tau), patients with normal CSF total tau levels (MCI low tau), and healthy control subjects. Linear mixed-model between-group within-subject analyses were conducted to examine differences in rate of change over time in FA and D(R). RESULTS: Longitudinal analysis of regional WM change revealed significant decrease in FA (P = .038) and increase in D(R) (P = .018) in the MCI high-tau group relative to control subjects. For D(R), the changes were regionally specific to the right cingulum and the right superior and inferior longitudinal fasciculi. CONCLUSION: Reduction in WM integrity was greater in patients with MCI who had the most intense neuronal degeneration as indexed by using CSF total tau, suggesting that these patients might represent a subgroup of MCI with more intense WM degeneration who are possibly at greater risk of developing Alzheimer disease.","Adult;Aged;Biomarkers/cerebrospinal fluid;Female;Humans;Longitudinal Studies;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Mild Cognitive Impairment/ cerebrospinal fluid/ pathology;Nerve Fibers, Myelinated/ pathology;Neurons/ pathology;Reproducibility of Results;Sensitivity and Specificity;Statistics as Topic;tau Proteins/ cerebrospinal fluid","Amlien, I. K.;Fjell, A. M.;Walhovd, K. B.;Selnes, P.;Stenset, V.;Grambaite, R.;Bjornerud, A.;Due-Tonnessen, P.;Skinningsrud, A.;Gjerstad, L.;Reinvang, I.;Fladby, T.",2013,Jan,10.1148/radiol.12120319,0,
5625,White matter lesions in FTLD: Distinct phenotypes characterize GRN and C9ORF72 mutations,,progranulin;amyotrophic lateral sclerosis;C9ORF72 gene;cardiovascular risk;clinical article;controlled study;disease duration;frontotemporal dementia;gene;gene mutation;human;informed consent;neuroimaging;neuroradiologist;note;nuclear magnetic resonance imaging;oligodendroglia;onset age;phenotype;priority journal;retrospective study;white matter lesion,"Ameur, F.;Colliot, O.;Caroppo, P.;Ströer, S.;Dormont, D.;Brice, A.;Azuar, C.;Dubois, B.;Le Ber, I.;Bertrand, A.",2016,,,0,
5626,Preliminary results of ASCOMALVA trial on the association of donepezil and choline alphoscerate in Alzheimer's disease with associated cerebrovascular injury,"This article summarizes the preliminary results of the ongoing (ASCOMALVA) trial on the ""association between a cholinesterase inhibitor (ChE-I) and a cholinergic precursor, choline alphoscerate on cognitive deficits in Alzheimer's disease associated with cerebrovascular injury"". The trial was designed to assess the effect of the ChE-I donepezil at the daily dose of 10 mg and of choline alphoscerate at the daily dose of 1,200 mg/day on the Mini Mental State Evaluation (MMSE), Basic Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Neuropsychiatric Inventory (NPI). The latter included an evaluation of severity and of caregiver stress (NPIF and NPIS). Currently, the trial has completed the first 6 months of follow-up on 70 of the 210 patients planned. Patients recruited were between 56 and 86 years of age (mean 75 ± 10 years) and were required to have a MMSE score between 15 and 24. Patients also needed to have ischemic brain lesions documented by neuroimaging (MRI and/or CT scan), with a score ≥ 2 in at least one subfield (white matter or basal ganglia) according to the New Rating Scale for Age-Related White Matter Changes (ARWMC). Patients were then randomly allocated to the active treatment group (donepezil + choline alphoscerate) or to a reference treatment group (donepezil + placebo). The first 70 patients included in this analysis have been followed for 6 months with evaluations at baseline and at 3 and 6 months. Treatment will be sustained for 24 months and evaluations will be conducted at 3, 6, 9, 12, 18 and 24 months. Patients in the reference treatment group displayed a slight, time- dependent worsening of MMSE, IADL and NPIS scores while there were no noticeable changes in ADL and NPIF scores. In contrast, treatment with donepezil plus choline alphoscerate did improve all of the different scores except for the ADL These preliminary results suggest that the addition of a cholinergic precursor like choline alphoscerate to the standard treatment with a ChE-I may represent a way to prolong/increase the beneficial effects of cholinergic therapies in Alzheimer's disease patients with concomitant ischemic cerebrovascular disease. © Società Italiana di Gerontologia e Geriatria.",choline alfoscerate;donepezil;placebo;adult;aged;Alzheimer disease;article;basal ganglion;brain ischemia;caregiver burden;cerebrovascular accident;computer assisted tomography;disease association;disease severity;drug effect;follow up;human;major clinical study;neuroimaging;nuclear magnetic resonance imaging;randomized controlled trial;treatment outcome;white matter,"Amenta, F.;Carotenuto, A.;Fasanaro, G.;Lanari, A.;Rea, R.;Traini, E.",2011,,,0,
5627,Preliminary results of ASCOMALVA trial on the association of donepezil and choline alphoscerate in Alzheimer's disease with associated cerebrovascular injury. Italian,"This article summarizes the preliminary results of the ongoing (ASCOMALVA) trial on the ""association between a cholinesterase inhibitor (ChE-I) and a cholinergic precursor, choline alphoscerate on cognitive deficits in Alzheimer's disease associated with cerebrovascular injury"". The trial was designed to assess the effect of the ChE-I donepezil at the daily dose of 10 mg and of choline alphoscerate at the daily dose of 1,200 mg/day on the Mini Mental State Evaluation (MMSE), Basic Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Neuropsychiatric Inventory (NPI). The latter included an evaluation of severity and of caregiver stress (NPIF and NPIS). Currently, the trial has completed the first 6 months of follow-up on 70 of the 210 patients planned. Patients recruited were between 56 and 86 years of age (mean 75 + 10 years) and were required to have a MMSE score between 15 and 24. Patients also needed to have ischemic brain lesions documented by neuroimaging (MRI and/or CT scan), with a score > 2 in at least one subfield (white matter or basal ganglia) according to the New Rating Scale for Age-Related White Matter Changes (ARWMC). Patients were then randomly allocated to the active treatment group (donepezil + choline alphoscerate) or to a reference treatment group (donepezil + placebo). The first 70 patients included in this analysis have been followed for 6 months with evaluations at baseline and at 3 and 6 months. Treatment will be sustained for 24 months and evaluations will be conducted at 3, 6, 9, 12, 18 and 24 months. Patients in the reference treatment group displayed a slight, time- dependent worsening of MMSE, IADL and NPIS scores while there were no noticeable changes in ADL and NPIF scores. In contrast, treatment with donepezil plus choline alphoscerate did improve all of the different scores except for the ADL These preliminary results suggest that the addition of a cholinergic precursor like choline alphoscerate to the standard treatment with a ChE-I may represent a way to prolong/increase the beneficial effects of cholinergic therapies in Alzheimer's disease patients with concomitant ischemic cerebrovascular disease. Societa Italiana di Gerontologia e Geriatria.",adult;aged;Alzheimer disease/dt [Drug Therapy];article;basal ganglion;brain ischemia;caregiver burden;cerebrovascular accident/dt [Drug Therapy];computer assisted tomography;disease association;disease severity;drug effect;follow up;human;major clinical study;neuroimaging;nuclear magnetic resonance imaging;randomized controlled trial;treatment outcome;white matter;choline alfoscerate/ct [Clinical Trial];choline alfoscerate/cb [Drug Combination];choline alfoscerate/dt [Drug Therapy];donepezil/ct [Clinical Trial];donepezil/cb [Drug Combination];donepezil/dt [Drug Therapy];placebo;Sr-dementia,"Amenta, F.;Carotenuto, A.;Fasanaro, G.;Lanari, A.;Rea, R.;Traini, E.",2011,,,0,
5628,The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results,"BACKGROUND: Cholinesterase inhibitors (ChE-Is) are among the drugs more largely used for the treatment of mild-to-moderate symptoms of Alzheimer's disease (AD), but beneficial long-term effects of these compounds on the cognitive, functional, and behavioural symptoms of the disease are small and not always apparent in practice. Preclinical investigations have suggested that association between ChE-Is and the cholinergic precursor choline alphoscerate enhances cholinergic neurotransmission more effectively than single compounds alone. The ongoing clinical trial on the ""Effect of association between a ChE-I and choline alphoscerate on cognitive deficits in Alzheimer's disease associated with cerebrovascular injury"" (ASCOMALVA) was designed to assess if association of the ChE-I donepezil with choline alphoscerate has a more favourable clinical profile than monotherapy with donepezil alone. METHODS: ASCOMALVA is a double-blind multicentre trial that has completed the first 12 months of observation of 91 patients of the 210 planned. Patients were aged between 56 and 91 years (mean 75 +/- 10 years) and were included in the protocol with a MMSE score between 15 and 24. Patients with AD diagnosed according to the DSM IV criteria suffer from ischemic brain damage documented by neuroimaging (MRI and CT scan), with a score>/=2 in at least one subfield of the New Rating Scale for Age-Related White Matter Changes (ARWMC). Patients were randomly allotted to an active treatment group (donepezil+choline alphoscerate) or to a reference treatment group (donepezil+placebo) and were examined after 3, 6, 9 and 12 months of treatment. RESULTS: Cognitive functions, patient's daily activities and behavioural symptoms were assessed by the Mini-Mental State Evaluation (MMSE), Alzheimer's Disease Assessment Scale Cognitive subscale (ADAS-cog), Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living (IADL) and Neuropsychiatric Inventory (NPI), of severity and of caregiver distress measures (NPI-F and NPI-D). Patients of the reference group (donepezil+placebo) showed along the course of the 12months of observation, a slight time-dependent worsening of MMSE, ADAS-cog, IADL and NPI-D scores and no changes in the BADL and NPI-F scores. Donepezil plus choline alphoscerate improved compared to donepezil alone the different items analysed except the BADL. CONCLUSIONS: The first results of the ASCOMALVA trial suggest that association of choline alphoscerate to the standard treatment with a ChE-I may represent an option to prolong beneficial effects of cholinergic therapies in AD with concomitant ischemic cerebrovascular injury.","Aged;Aged, 80 and over;Alzheimer Disease/complications/*drug therapy;Cerebrovascular Disorders/complications/*drug therapy;Double-Blind Method;Female;Follow-Up Studies;Glycerylphosphorylcholine/*therapeutic use;Humans;Indans/*therapeutic use;Male;Mental Status Schedule;Middle Aged;Nootropic Agents/*therapeutic use;Piperidines/*therapeutic use;Treatment Outcome","Amenta, F.;Carotenuto, A.;Fasanaro, A. M.;Rea, R.;Traini, E.",2012,Nov 15,10.1016/j.jns.2012.07.003,0,
5629,Insidious cognitive decline in CADASIL,"BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL. METHODS: Prestroke (n=13) and poststroke (n=13) mutation carriers and mutation carriers with dementia (n=8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests. RESULTS: Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease. CONCLUSIONS: A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.","Adult;*Cognition;Cross-Sectional Studies;Dementia, Multi-Infarct/*genetics/*physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Memory;Middle Aged;Mutation;Neuropsychological Tests;Pedigree;Proto-Oncogene Proteins/*genetics;Receptors, Cell Surface/*genetics;Receptors, Notch","Amberla, K.;Waljas, M.;Tuominen, S.;Almkvist, O.;Poyhonen, M.;Tuisku, S.;Kalimo, H.;Viitanen, M.",2004,Jul,10.1161/01.STR.0000129787.92085.0a,0,
5630,"Manual segmentation of the fornix, fimbria, and alveus on high-resolution 3T MRI: Application via fully-automated mapping of the human memory circuit white and grey matter in healthy and pathological aging","Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the alveus and cornu ammonis (CA) 1 were well preserved (all p's<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required.",Ad;Anatomy;Hippocampus;Mci;Segmentation;White matter,"Amaral, R. S.;Park, M. T.;Devenyi, G. A.;Lynn, V.;Pipitone, J.;Winterburn, J.;Chavez, S.;Schira, M.;Lobaugh, N. J.;Voineskos, A. N.;Pruessner, J. C.;Chakravarty, M. M.;Alzheimer's Disease Neuroimaging, Initiative",2016,Oct 18,,0,
5631,"The presence of leuko-araiosis in patients with Alzheimer's disease predicts poor tolerance to tacrine, but does not discriminate responders from non-responders","BACKGROUND: approximately one-third of patients with Alzheimer's disease (AD) respond favourably to the anticholinesterase tacrine, but the drug's usefulness is marred by a high incidence of side-effects. OBJECTIVE: to discover if AD patients with white matter low attenuation (WMLA) represents a subgroup that responds differently to tacrine from those with no WMLA. DESIGN: the results come from a combination of double-blind and open studies. Seventy-two AD patients prescribed tacrine in our centre were divided into two groups according to the presence or absence of WMLA on brain CT scans. We compared the rate of response to and withdrawal from tacrine between the groups. Response was defined as an improvement in the Mini-Mental State Examination score of three or more points at 3 months. RESULTS: 18 of the 72 patients were found to have WMLA. There was no significant difference in the proportion of patients responding to tacrine in each group (28.5% in those with WMLA and 31% in those without), but the rate of withdrawal from tacrine did differ: 11 patients with WMLA (61%) had to be withdrawn prematurely, compared with 14 patients (26%) in the group without evidence of WMLA (P = 0.015). CONCLUSION: AD patients with WMLA can still respond to tacrine, although the rate of withdrawal from treatment is much higher in such patients.",Alzheimer Disease/*drug therapy/pathology;Brain/pathology;Brain Ischemia/*drug therapy/pathology;Demyelinating Diseases/*drug therapy/pathology;Double-Blind Method;Female;Geriatric Assessment;Humans;Male;Mental Status Schedule;Nootropic Agents/*adverse effects/therapeutic use;Prognosis;Risk Factors;Tacrine/*adverse effects/therapeutic use,"Amar, K.;Wilcock, G. K.;Scot, M.;Lewis, T.",1997,Jan,,0,
5632,Are genetic factors important in the aetiology of leukoaraiosis? Results from a memory clinic population,"OBJECTIVE: To discover whether polymorphism in either the apolipoprotein E (ApoE) or angiotensin-converting enzyme (ACE) genes is associated with leukoaraiosis, white matter lesions visible on neuroimaging of the brain, which is commonly seen in dementia as well as some normal elderly subjects. DESIGN: Prospective study of consecutive patients attending our memory disorders clinic, to examine the relationship between leukoaraiosis and polymorphism of the ApoE and ACE genes. SETTING: Memory disorders clinic in Bristol, UK. PATIENTS: 182 patients attending the memory disorders clinic for investigation of possible dementia of whom 75% were suffering from dementia, 20% from memory impairment but no dementia and in 5% of whom a dementing illness was thought to be unlikely; 38% of all patients had visible white matter lesions and 16% had cerebral infarcts. MEASURES: Patients and/or carers who agreed to participate in the study had their ACE and ApoE genotype determined and their brain CT/MRI scans were assessed by a neuroradiologist, blind to the result of the genotyping, for the presence or absence of white matter low attenuation. RESULTS: There was a significant association between white matter lesions and the DD genotype (p < 0.05), but not the ApoE genotype. However, this relationship with the DD genotype was only significant for patients with a previous infarct. CONCLUSION: Homozygosity of ACE gene deletion polymorphism is a risk factor for white matter lesions when it is associated with cerebral infarction. This suggests that it may be possible to identify subjects who are at greater risk of developing white matter lesions and are at risk of cognitive impairment and possibly dementia.","Aged;Apolipoproteins E/genetics;Brain/pathology;Brain Diseases/*genetics/pathology;Cerebral Infarction/genetics/pathology;Genotype;Humans;Memory Disorders/pathology;Peptidyl-Dipeptidase A/genetics;Polymorphism, Genetic","Amar, K.;MacGowan, S.;Wilcock, G.;Lewis, T.;Scott, M.",1998,Sep,,0,
5633,The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic study,"In order to discover the prevalence of white matter low attenuation (WMLA) in the brain and its relationship to vascular risk factors in our Memory Disorders Clinic patients we assessed brain CT scans of 202 patients referred to our clinic between January 1991 and December 1992. One hundred patients (49.5%) had WMLA, and the prevalence increased with increasing severity of cognitive impairment. It was 12% in patients with no evidence of dementia, 32% in those with isolated memory loss, and 59%) in patients with possible or probable dementia. There was a correlation between WMLA and systolic blood pressure, heart disease, peripheral vascular disease, focal neurological signs on examination and central atrophy on CT. No correlation was found between WMLA and low blood pressure, blood glucose or cholesterol level. Our findings indicate that WMLA probably plays an important role in cognitive impairment, and that thromboembolic rather than haemodynamic factors are probably more important in its pathogenesis.","Aged;Brain Diseases/diagnosis;Dementia/diagnosis;Diagnosis, Differential;Female;Humans;Male;Memory Disorders/*diagnosis/*physiopathology;Middle Aged;*Prevalence;Risk Factors;Statistics as Topic;*Tomography, X-Ray Computed;Vascular Diseases/*diagnosis","Amar, K.;Lewis, T.;Wilcock, G.;Scott, M.;Bucks, R.",1995,Sep,,0,
5634,The effect of white matter low attenuation on cognitive performance in dementia of the Alzheimer type,"The effect of leukoaraiosis or white matter low attenuation (WMLA) on cognitive function is not fully understood. We compared the neuropsychological performance of 37 Alzheimer's disease patients with WMLA on CT brain scans with a similar group of 31 Alzheimer's disease patients with no evidence of white matter lesions. Patients with WMLA performed significantly worse on tests of visuospatial function (Cube Analysis test, p = 0.004), and cognitive speed (Kenrick Digit Copying test, p = 0.05) compared to those with no visible white matter lesions. Patients with widespread WMLA performed generally worse in tests of cognitive function than those with frontal or a mixture of frontal and occipital WMLA. This was most significant in the areas of attention (forward digit span, p = 0.003), visual recognition (p = 0.004), and cognitive speed (p = 0.03). There is an association between impaired cognitive performance and the presence of WMLA in Alzheimer's disease patients, with WMLA probably contributing to the cognitive impairment. This is most evident in patients with widespread white matter lesions.","Aged;Aged, 80 and over;Alzheimer Disease/*diagnosis;Attention/physiology;Cerebral Cortex/*pathology;Female;Geriatric Assessment;Humans;Male;Mental Recall/physiology;*Neuropsychological Tests;Pattern Recognition, Visual/physiology;Reaction Time/physiology;*Tomography, X-Ray Computed","Amar, K.;Bucks, R. S.;Lewis, T.;Scott, M.;Wilcock, G. K.",1996,Nov,,0,
5635,Stable xenon CT cerebral blood flow measurements computed by a single compartment--double integration model in normal aging and dementia,"Programs have been developed, using a single compartmental analysis model, that provide rapid computer derivation for values of both local cerebral blood flows (LCBF) and local tissue: blood partition coefficients (L lambda) using inhaled stable xenon gas (Xes) as the indicator. These programs are planned for utilization of raw data points derived from serial computed tomography scans made between the 3rd and 9th min after 35% Xes inhalation, while concentrations of end-tidal Xes (PEXes) are concurrently monitored. Double integration and least squares fitting permitted estimation of corresponding arterial (assumed from PEXes) and tissue Xes concentrations at each scanning interval during Xes saturation. Derived estimates for L lambda and LCBF values for each region of interest mathematically approximate values saturated to infinity. The method described can be utilized for any freely diffusible indicator. Cross-sectional analysis of results obtained in 13 normal healthy volunteers between 20 and 80 years of age showed no age-related changes in L lambda values but progressive decreases in blood flow of cortex, basal ganglia, and white matter with advancing age. In senile dementia of Alzheimer's type (SDAT, n = 8) L lambda values were likewise found to be unchanged, but cortical and thalamic gray matter LCBF values were significantly reduced compared to age-matched normal volunteers.","Adult;Aged;*Aging;Alzheimer Disease/*radionuclide imaging;*Cerebrovascular Circulation;Dementia/*radionuclide imaging;Female;Humans;Male;Middle Aged;Tomography, Emission-Computed/*methods","Amano, T.;Meyer, J. S.;Okabe, T.;Shaw, T.;Mortel, K. F.",1982,Oct,,0,
5636,Different patterns of white matter degeneration using multiple diffusion indices and volumetric data in mild cognitive impairment and Alzheimer patients,"Alzheimers disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.","Aged;Aged, 80 and over;Alzheimer Disease/ pathology;Anisotropy;Brain Mapping;Case-Control Studies;Corpus Callosum/ pathology/physiopathology;Diffusion;Diffusion Tensor Imaging;Female;Gyrus Cinguli/pathology/physiopathology;Hippocampus/ pathology/physiopathology;Humans;Male;Mild Cognitive Impairment/ pathology;Multivariate Analysis;Organ Size;Wallerian Degeneration/pathology","Alves, G. S.;O'Dwyer, L.;Jurcoane, A.;Oertel-Knochel, V.;Knochel, C.;Prvulovic, D.;Sudo, F.;Alves, C. E.;Valente, L.;Moreira, D.;Fusser, F.;Karakaya, T.;Pantel, J.;Engelhardt, E.;Laks, J.",2012,,10.1371/journal.pone.0052859,0,
5637,Association of microstructural white matter abnormalities with cognitive dysfunction in geriatric patients with major depression,"Major depression disorder (MDD) is one of the most common causes of disability in people over 60years of age. Previous studies have linked affective and cognitive symptoms of MDD to white matter (WM) disruption in limbic-cortical circuits. However, the relationship between clinical cognitive deficits and loss of integrity in particular WM tracts is poorly understood. Fractional anisotropy (FA) as a measure of WM integrity was investigated in 17 elderly MDD subjects in comparison with 18 age-matched controls using tract-based spatial statistics (TBSS) and correlated with clinical and cognitive parameters. MDD patients revealed significantly reduced FA in the right posterior cingulate cluster (PCC) compared with controls. FA in the right PCC (but not in the left PCC) showed a significant positive correlation with performance in a verbal naming task, and showed a non-significant trend toward a correlation with verbal fluency and episodic memory performance. In control subjects, no correlations were found between cognitive tasks and FA values either in the right or left PCC. Results provide additional evidence supporting the neuronal disconnection hypothesis in MDD and suggest that cognitive deficits are related to the loss of integrity in WM tracts associated with the disorder.","Aged;Alzheimer Disease/diagnosis/pathology/psychology;Brain/*pathology;Brain Mapping;Cerebral Cortex/pathology;Cognition Disorders/diagnosis/*pathology/psychology;Depressive Disorder, Major/diagnosis/*pathology/psychology;*Diffusion Magnetic Resonance Imaging;Disease Progression;Dominance, Cerebral/physiology;Female;Gyrus Cinguli/*pathology;Humans;*Image Interpretation, Computer-Assisted;Leukoencephalopathies/diagnosis/*pathology/psychology;Limbic System/pathology;Male;Middle Aged;Nerve Fibers/*pathology;Nerve Net/*pathology;Neuropsychological Tests/statistics & numerical data;Psychometrics;Reference Values","Alves, G. S.;Karakaya, T.;Fusser, F.;Kordulla, M.;O'Dwyer, L.;Christl, J.;Magerkurth, J.;Oertel-Knochel, V.;Knochel, C.;Prvulovic, D.;Jurcoane, A.;Laks, J.;Engelhardt, E.;Hampel, H.;Pantel, J.",2012,Aug-Sep,10.1016/j.pscychresns.2011.12.006,0,
5638,A panel of clinical and neuropathological features of cerebrovascular disease through the novel neuroimaging methods,"The last decade has witnessed substantial progress in acquiring diagnostic biomarkers for the diagnostic workup of cerebrovascular disease (CVD). Advanced neuroimaging methods not only provide a strategic contribution for the differential diagnosis of vascular dementia (VaD) and vascular cognitive impairment (VCI), but also help elucidate the pathophysiological mechanisms ultimately leading to small vessel disease (SVD) throughout its course. Objective: In this review, the novel imaging methods, both structural and metabolic, were summarized and their impact on the diagnostic workup of age-related CVD was analysed. Methods: An electronic search between January 2010 and 2017 was carried out on PubMed/MEDLINE, Institute for Scientific Information Web of Knowledge and EMBASE. Results: The use of full functional multimodality in simultaneous Magnetic Resonance (MR)/Positron emission tomography (PET) may potentially improve the clinical characterization of VCI-VaD; for structural imaging, MRI at 3.0 T enables higher-resolution scanning with greater imaging matrices, thinner slices and more detail on the anatomical structure of vascular lesions. Conclusion: Although the importance of most of these techniques in the clinical setting has yet to be recognized, there is great expectancy in achieving earlier and more refined therapeutic interventions for the effective management of VCI-VaD.",Dti;Mri;Pet;diffusion tensor imaging;neuroimaging;novel methods;vascular,"Alves, G. S.;de Carvalho, L. A.;Sudo, F. K.;Briand, L.;Laks, J.;Engelhardt, E.",2017,Oct-Dec,,0,
5639,Clinical characteristics in subcortical ischemic white matter disease,"BACKGROUND: Vascular white matter lesions (WML) represent one of the main neuroimage findings in individuals older than 65 years and its clinical significance is still partially understood. OBJECTIVE: To describe and analyze the clinical profile of a high severity sample with WML focusing on the frontal executive control. METHOD: Outpatients (n=20) with high severity WML evaluated with magnetic resonance imaging were selected using the Fazekas scale. RESULTS: Most patients (n=17; 85%) presented an altered Trail Making Test ratio (section B/section A); on verbal fluency, 15 individuals (75%) performed below the cutoff score. Apathy (5.9 +/- 4.65) and depression (3.05+/-3.67) were frequent as assessed by the Neuropsychiatric Inventory. The impairment in functional activities strongly correlated with apathy (r=0.814, p<0.001) and verbal fluency (r=0.744, p<0.001). CONCLUSION: Executive dysfunction, apathy, and ratio depression were the main characteristics found. Extension of WML may have distinct impact on the clinical picture, but further studies with methodological adjustments are necessary to provide more definitive conclusions.","Aged;Brain/pathology/physiopathology;Cognition Disorders/diagnosis/ etiology;Cross-Sectional Studies;Dementia, Vascular/ complications/pathology/physiopathology;Executive Function/physiology;Female;Humans;Magnetic Resonance Imaging;Male;Mental Disorders/diagnosis/ etiology;Neuropsychological Tests;Severity of Illness Index","Alves, G. S.;Alves, C. E.;Lanna, M. E.;Ericeira-Valente, L.;Sudo, F. K.;Moreira, D.;Engelhardt, E.;Laks, J.",2009,Jun,,0,
5640,Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity: Follow up of two cases,"Introduction: The geriatric depression (GD) represents one of the most frequent psychiatric disorders in outpatient services specialized in old-age treatment. Objective: The course of two illustrative cases of GD is discussed, highlighting its clinical picture after antidepressant treatment and underlining variables related to disease prognosis, treatment effectiveness and conversion to major cognitive disorders such as vascular dementia (VD). Methods: The cognitive performance, depressive symptoms, autonomy and brain structural measurements as white matter hyperintensities (WMH) and hippocampal size, and microstructural integrity of WM with diffusion tensor imaging were followed during four years. Results: Case 1, with a severe degree of WMH, was associated with worsening cognition and increasing functional disability. Case 2, with mild WMH, an improvement of cognitive functioning could be seen. Conclusions: The existence of different subtypes of GD, as presented in this report, points a pathophysiological heterogeneity of GD, and suggests a possible continuum vascular depression (VaDp) and vascular cognitive impairment (VCI).",,"Alves, C. E. O.;Alves, G. S.;Sudo, F. K.;Lanna, M. E.;Ericeira-Valente, L.;Moreira, D. M.;Laks, J.;Engelhardt, E.",2012,January,,0,
5641,MicroRNA expression profiling in blood from fragile X-associated tremor/ataxia syndrome patients,"Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with FMR1 gene premutation alleles (55-200 CGG repeats). Fragile X-associated tremor/ataxia syndrome clinical core features include action tremor, gait ataxia, cognitive deficits progressing to dementia, and frequently parkinsonism. Although the pathogenic molecular mechanism of FXTAS is not completely understood, the restriction of the phenotype to the FMR1 premutation range has given rise to a model based on a RNA toxic gain-of-function. Since the identification of the first microRNAs (miRNAs) and their role in normal development, several studies have associated them with neurodegenerative diseases such as Parkinson, Alzheimer and Huntington diseases, suggesting that they play a key role in brain development, as well as in its morphogenesis. Herein, we present the characterization of miRNA expression profiles in FXTAS male patients using deep sequencing-based technologies and microarray technology. Deep sequencing analysis evidenced 83 miRNAs that were significantly deregulated whereas microarray analysis showed 31. When comparing these results, 14 miRNAs were found deregulated in FXTAS patients. MiR-424 and miR-574-3p showed significant fold change adjusted P-values in both platforms in FXTAS patients. MiR-424 has been founded substantially and specifically enriched in human cerebral cortical white matter of Alzheimer disease patients, which, together with cerebral atrophy, is a prominent imaging finding in individuals with FXTAS. The study provides the first systematic evidence of differential miRNA expression changes in FXTAS blood samples. Although further studies are necessary to better characterize the miRNA function in FXTAS disorder, our results suggest that they might contribute to its pathogenesis.","Aged;Case-Control Studies;Cerebellar Diseases/diagnosis/genetics;Fragile X Mental Retardation Protein/genetics;Gene Expression Profiling;High-Throughput Nucleotide Sequencing;Humans;Male;MicroRNAs/ blood/chemistry;Middle Aged;Oligonucleotide Array Sequence Analysis;Sequence Analysis, DNA","Alvarez-Mora, M. I.;Rodriguez-Revenga, L.;Madrigal, I.;Torres-Silva, F.;Mateu-Huertas, E.;Lizano, E.;Friedlander, M. R.;Marti, E.;Estivill, X.;Mila, M.",2013,Aug,10.1111/gbb.12061,0,
5642,Multimodal retinal vessel analysis in CADASIL patients,"PURPOSE: To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging. METHODS: 28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT. RESULTS: Mean age of patients was 56.2 +/- 11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77 +/- 0.46 mm(3) and 8.83 +/- 2.24 mm(3). RNFL measurements showed a global increase of 105.2 microm ( CONTROL GROUP: 98.4 microm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 microm (106.0 microm; p = 0.21) and 128.6 microm (124.4 microm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 microm (125.4 microm; p<0.001) and venous 160.0 microm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 microm (19.2 microm; p<0.001) and venous 18.3 microm (15.7 microm; p<0.001) wall thicknesses in CADASIL patients. CONCLUSIONS: The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases.","Aged;Angiography;CADASIL/ pathology;Humans;Middle Aged;Retinal Vessels/ pathology;Tomography, Optical Coherence","Alten, F.;Motte, J.;Ewering, C.;Osada, N.;Clemens, C. R.;Kadas, E. M.;Eter, N.;Paul, F.;Marziniak, M.",2014,,10.1371/journal.pone.0112311,0,
5643,Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer's Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline,"BACKGROUND: Growing evidence suggests that the endocannabinoid system is involved in the pathogenesis of Alzheimer's disease (AD) and atherosclerosis. OBJECTIVE: The purpose of this study was to investigate the activation of the endocannabinoid system in AD in vivo and the possible intermediate role of atherosclerosis. METHODS: We enrolled 41 patients with probable AD, and 30 age- and gender-matched controls. All subjects underwent: ultrasound examination of cerebral and neck vessels (including intima-media thickness and plaque stenosis evaluation); blood sampling to measure levels of endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and endogenous AEA analogues [N-palmitoyl-ethanolamide (PEA); N-oleoyl-ethanolamide]; neuropsychological evaluation and brain MRI (atrophy, white matter hyperintensity volume). RESULTS: 2-AG levels were higher in AD patients compared to controls (Mann-Whitney test p = 0.021). In the AD group, 2-AG correlated to white matter hyperintensity volume (r = 0.415, p = 0.015) and was higher in patients with chronic heart ischemic disease (p = 0.023). In AD patients, 2-AG was also positively related to memory (r = 0.334, p = 0.05) and attention (r = 0.423, p = 0.018) performances. Constructional praxia test scores were lower in patients with higher levels of PEA (r =-0.389, p = 0.019). CONCLUSION: AD patients present high plasma 2-AG levels, also in relation to heart ischemic disease and cerebral leukoaraiosis. This may be a protective mechanism hindering neurodegeneration, but it may also play an ambivalent role on cerebrovascular circulation. The increase in 2-AG and PEA levels observed with ongoing pathological processes may differently modulate cognitive performances.",Alzheimer's disease;atherosclerosis;endocannabinoids;leukoaraiosis,"Altamura, C.;Ventriglia, M.;Martini, M. G.;Montesano, D.;Errante, Y.;Piscitelli, F.;Scrascia, F.;Quattrocchi, C.;Palazzo, P.;Seccia, S.;Vernieri, F.;Di Marzo, V.",2015,,10.3233/jad-142349,0,
5644,"Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia","BACKGROUND AND PURPOSE: An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. METHODS: Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). RESULTS: Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. CONCLUSIONS: Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains.",,"Altamura, C.;Scrascia, F.;Quattrocchi, C. C.;Errante, Y.;Gangemi, E.;Curcio, G.;Ursini, F.;Silvestrini, M.;Maggio, P.;Beomonte Zobel, B.;Rossini, P. M.;Pasqualetti, P.;Falsetti, L.;Vernieri, F.",2016,Apr,10.3988/jcn.2016.12.2.201,0,
5645,White matter signal abnormalities in former National Football League players,"Introduction: Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players. Methods: Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs. Results: In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores (P = .043) and worse psychomotor speed and executive function (P = .015). Although former NFL players had greater WMSA volume than controls (P = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure. Discussion: In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.",Alzheimer's disease;Chronic traumatic encephalopathy;Cognitive function;Concussion;Repetitive head impacts;Subconcussive;White matter hyperintensities;White matter signal abnormalities,"Alosco, M. L.;Koerte, I. K.;Tripodis, Y.;Mariani, M.;Chua, A. S.;Jarnagin, J.;Rahimpour, Y.;Puzo, C.;Healy, R. C.;Martin, B.;Chaisson, C. E.;Cantu, R. C.;Au, R.;McClean, M.;McKee, A. C.;Lin, A. P.;Shenton, M. E.;Killiany, R. J.;Stern, R. A.",2018,,,0,
5646,Structural brain alterations in heart failure: a review of the literature and implications for risk of Alzheimer's disease,"Cardiovascular disease is a recognized contributor to the pathogenesis of Alzheimer's disease (AD). Heart failure (HF) is a cardiovascular subtype that can be used to model the contribution of cardiovascular disease to AD. Neuroimaging research indicates that HF patients exhibit a diverse range of structural brain alterations and epidemiological studies suggest HF may be an important risk factor for AD. The neural alterations observed in HF may overlap with those observed in AD and contribute to increased risk of AD in HF patients. To examine this possibility, we reviewed structural MRI studies in persons with HF. We examined subcortical brain regions affected in the early stages of AD (medial temporal lobes), as well as cortical alterations that typically occur in the later stages of AD. Our review indicates that patients with HF exhibit greater neural atrophy and white matter microstructural alterations of nearly every region of the Papez circuit (e.g., hippocampus, cingulate gyrus, thalamus, mammillary bodies, and fornix), as well-significant alterations in cortical and cerebellar regions. Based on animal research and past work in AD patients, the mechanisms for structural brain changes in HF may stem from reductions in cerebral blood flow subsequent to cardiac deficiency. This review supports the hypothesis that HF may contribute to AD risk via widespread structural brain changes, including many of the same regions affected by AD. Case-controlled prospective neuroimaging studies with long-term follow-ups are needed to clarify the risk of AD in HF and elucidate the neural underpinnings of AD risk in HF.",,"Alosco, M. L.;Hayes, S. M.",2015,Sep,10.1007/s10741-015-9488-5,0,
5647,Independent and interactive effects of blood pressure and cardiac function on brain volume and white matter hyperintensities in heart failure,"BACKGROUND: Reduced systemic perfusion and comorbid medical conditions are key contributors to adverse brain changes in heart failure (HF). Hypertension, the most common co-occurring condition in HF, accelerates brain atrophy in aging populations. However, the independent and interactive effects of blood pressure and systemic perfusion on brain structure in HF have yet to be investigated. METHODS: Forty-eight older adults with HF underwent impedance cardiography to assess current systolic blood pressure status and cardiac index to quantify systemic perfusion. All participants underwent brain magnetic resonance imaging to quantify total brain, total and subcortical gray matter volume, and white matter hyperintensities (WMH) volume. RESULTS: Regression analyses adjusting for medical and demographic factors showed decreased cardiac index was associated with smaller subcortical gray matter volume (P < .01), and higher systolic blood pressure predicted reduced total gray matter volume (P = .03). The combination of higher blood pressure and lower cardiac index exacerbated WMH (P = .048). CONCLUSIONS: Higher blood pressure and systemic hypoperfusion are associated with smaller brain volume, and these factors interact to exacerbate WMH in HF. Prospective studies are needed to clarify the effects of blood pressure on the brain in HF, including the role of long-term blood pressure fluctuations.","Aged;Aged, 80 and over;Atrophy/epidemiology/pathology/physiopathology;Blood Pressure/ physiology;Comorbidity;Dementia/epidemiology/pathology/ physiopathology;Female;Heart Failure/epidemiology/ physiopathology;Heart Function Tests;Humans;Hypertension/epidemiology/ physiopathology;Leukoencephalopathies/epidemiology/pathology/ physiopathology;Magnetic Resonance Imaging;Male;Mental Disorders/epidemiology/pathology/ physiopathology;Middle Aged","Alosco, M. L.;Brickman, A. M.;Spitznagel, M. B.;Griffith, E. Y.;Narkhede, A.;Raz, N.;Cohen, R.;Sweet, L. H.;Hughes, J.;Rosneck, J.;Gunstad, J.",2013,Sep-Oct,10.1016/j.jash.2013.04.011,0,
5648,A case of anxiety associated with miliary tuberculosis,"Miliary tuberculosis (TB) is a serious infection with various presentations that can perplex even the most experienced clinicians. To our knowledge, there is a lack of published reports that link psychiatric symptoms directly with miliary TB (either alone or co-occurring with other medical symptoms). Mental health workers may, therefore, not consider, and consequently miss, this important diagnosis. Here we are reporting a case of cyclical anxiety occurring in a 67-year-old patient. For 3 years prior to admission, the patient failed to respond to multiple courses of different antianxiety medications. The patient required hospital admission as he deteriorated and had a reduced level of consciousness. A chest X-ray revealed bilateral nodules and a magnetic resonance imaging scan showed multiple enhancing tuberculous lesions in the cerebral white matter, brain stem, and cerebellum. A diagnosis of miliary TB was finally made. Several characteristics of this case suggest that the diagnosed anxiety disorder was due to miliary TB. However, we cannot exclude the possibility that generalized anxiety disorder preceded the onset of miliary TB or that both diseases were coincidental. The report serves as a reminder that organic causes for psychiatric symptoms always need to be considered, particularly if they follow an atypical pattern or fail to improve with usual psychiatric medications. © 2014 Alosaimi et al. This work is published by Dove Medical Press Limited.",,"Alosaimi, F. D.;Alkharboush, F. A.;Altuwariqi, M. H.",2014,20,,0,
5649,White-matter hyperintensity and neuropsychological functions in dementia and healthy aging,"The relationship between quantitative measurements of brain white-matter hyperintensity (WMH), assessed by magnetic resonance imaging and neuropsychological functions, was explored in demented patients and healthy aged individuals with and without WMH in 12 brain regions. The prevalence of WMH was significantly higher in vascular dementia compared with Alzheimer's disease, especially in posterior periventricular regions. Results showed no difference in any neuropsychological measurement between healthy aged adults with and without WMH. The demented patients with WMH were more impaired in tests of visuoconstruction, attention, finger-motor speed, and latency of tactile identification of objects compared with patients without WMH. These impairments were related mainly to posterior periventricular WMH. There was no relationship between WMH and global cognitive functioning in the demented patients. The degree of WMH was related to age and blood pressure. The data suggest that specific regional WMH may result in specific neuropsychological impairments.",Aged;Aging;Brain/anatomy & histology/ pathology;Dementia/ pathology/psychology;Female;Humans;Magnetic Resonance Imaging;Male;Neuropsychological Tests,"Almkvist, O.;Wahlund, L. O.;Andersson-Lundman, G.;Basun, H.;Backman, L.",1992,Jun,,0,
5650,Clinical findings in nondemented mutation carriers predisposed to Alzheimer's disease: a model of mild cognitive impairment,"Individuals carrying a mutation associated with Alzheimer's disease (AD) may serve as a model of mild cognitive impairment (MCI). Nondemented individuals from these families can be subdivided into asymptomatic and symptomatic groups. Four families were studied. Two families are associated with APP mutations (KN670/671ML, E693G) and two with PS1 mutation (M146V, H163Y). Clinical symptoms, level of global cognitive functioning as evaluated by Mini-Mental State Examination, neuropsychological test results, neuroradiological examinations (magnetic resonance imaging (MRI) and single-photon emission tomography (SPECT)), as well as cerebrospinal fluid (CSF) measurements of tau and beta-amyloid are reported. Nondemented mutation carriers did not report any symptoms indicating cognitive decline. In addition, no clinical signs of dementia or marked cognitive impairment in neuropsychological tests were found. A reduction of temporal blood flow with SPECT was indicated in 5/13 nondemented mutation carriers. Two of these 13 individuals had moderate hyperintensities in deep white matter as observed on MRI. CSF measurements of A beta 42/43 were inconclusive because of large biological variation. A nonsignificant elevation of tau was detected in mutation carriers. In conclusion, clinical examinations of relatively young individuals carrying an AD mutation did not reveal any marked abnormalities before the clinical onset of dementia.","Adolescent;Adult;Age of Onset;Aged;Alzheimer Disease/ diagnosis/epidemiology/ genetics;Amyloid beta-Peptides/cerebrospinal fluid;Amyloid beta-Protein Precursor/genetics;Cognition Disorders/ diagnosis/epidemiology/ genetics;Comorbidity;Disease Progression;Genes, Dominant;Genetic Predisposition to Disease;Heterozygote;Humans;Magnetic Resonance Imaging;Membrane Proteins/genetics;Middle Aged;Mutation;Neuropsychological Tests;Presenilin-1;Sweden/epidemiology;Temporal Lobe/blood supply/radionuclide imaging;Tomography, Emission-Computed, Single-Photon;tau Proteins/cerebrospinal fluid","Almkvist, O.;Axelman, K.;Basun, H.;Jensen, M.;Viitanen, M.;Wahlund, L. O.;Lannfelt, L.",2003,,,0,
5651,Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain,"White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (gammaH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). gammaH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated beta-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined.",,"Al-Mashhadi, S.;Simpson, J. E.;Heath, P. R.;Dickman, M.;Forster, G.;Matthews, F. E.;Brayne, C.;Ince, P. G.;Wharton, S. B.",2015,Sep,10.1111/bpa.12216,0,
5652,Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up,"BACKGROUND: Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure. AIMS: To examine lifetime blood pressure as a predictor of brain structure in old age. METHOD: A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985-2013). In 2012-2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities. RESULTS: Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy. CONCLUSIONS: Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose-response pattern.","Age Distribution;Aged;Aged, 80 and over;Atrophy;Blood Pressure;Brain/ radionuclide imaging;Cognition Disorders/complications;Cohort Studies;Cross-Sectional Studies;Dementia/complications;Depressive Disorder/complications;Female;Follow-Up Studies;Humans;Hypertension/ complications/ diagnosis;Magnetic Resonance Imaging;Male;Middle Aged;Risk Factors;Sex Distribution","Allan, C. L.;Zsoldos, E.;Filippini, N.;Sexton, C. E.;Topiwala, A.;Valkanova, V.;Singh-Manoux, A.;Tabak, A. G.;Shipley, M. J.;Mackay, C.;Ebmeier, K. P.;Kivimaki, M.",2015,Apr,10.1192/bjp.bp.114.153536,0,
5653,Brain comorbidities in normal pressure hydrocephalus,"BACKGROUND AND PURPOSE: This cross-sectional study aims to compare gait changes after the cerebrospinal fluid (CSF) tap test between normal pressure hydrocephalus patients with and without brain comorbidities (NPH+ and NPH- respectively) and then to identify significant contributors to a poor CSF tap test amongst individuals with NPH+. METHODS: Gait changes (during the single task and the dual task of backward counting) were quantified before and 24 h after the CSF tap test with an optoelectronic system in 52 NPH patients (77.4 +/- 6.0 years; 34.6% women). Changes after the CSF tap test in stride time variability (STV, %) were our main outcome. CSF Alzheimer's disease biomarkers, cerebrovascular white matter changes assessed with brain imaging and neurodegenerative diseases with parkinsonian syndrome represented the three individual brain comorbidities. RESULTS: Brain comorbidities were frequently identified, NPH+ patients representing 40 patients of our sample (76.9%). NPH- patients improved their STV better in the single task (delta of STV = -58.6% +/- 54.3% vs. -14.1% +/- 62.0%; P = 0.031) and in the dual task (delta of STV =-32.2% +/- 33.7% vs. 6.3% +/- 58.4%; P = 0.028) after the CSF tap test than NPH+ patients. Amongst NPH+ individuals, only comorbid Alzheimer's disease was associated with STV increase (i.e. deterioration of gait) in the dual task [beta 38.4; 95% confidence interval (5.64; 71.24); P = 0.023] after the CSF tap test, whilst it was borderline in the single task [beta 35.0; 95% confidence interval (-1.97; 71.90); P = 0.063]. CONCLUSIONS: Brain comorbidities affect gait improvement after the CSF tap test in NPH patients; this influence is driven by Alzheimer's disease-related pathology.",biomarkers;comorbidity;dementia;gait disorders;normal pressure hydrocephalus,"Allali, G.;Laidet, M.;Armand, S.;Assal, F.",2017,Dec 9,,0,
5654,"Pattern of vascular dementia in India: study of clinical features, imaging, and vascular mechanisms from a hospital dementia registry","Vascular dementia (VaD) is heterogeneous in its clinical, imaging, and etiological characteristics. Although VaD is common in India, its pattern is not completely known. In a hospital-based cohort, we aimed to characterize VaD by its subtypes and study patterns of risk factors and clinical, and neuropsychological profiles. Vascular mechanisms, known to have racial and genetic variations were identified. NINDS-AIREN criteria were used to diagnose VaD. Patients were subtyped into subcortical, cortical, cortical-subcortical, and strategic infarct dementia. Vascular mechanisms were detected by vascular imaging, cardiac evaluation, and laboratory tests. In the 42 consecutive patients with VaD, subcortical dementia was the most common type (52.4%), followed by cortical-subcortical (26.2%), strategic infarcts in (14.3%), and cortical dementia (7.1%). Stroke (81%), hypertension (71.4%), and diabetes (35.7%) were important risk factors. Small artery disease was the underlying vascular mechanism in 42.9%; intracranial large artery disease, in 16.7%; extracranial disease, in 2.3%; cardioembolism, in 2.3%; multiple mechanisms, in 19%; and unknown, in 16.7%. Subtypes were similar in risk factor profile and neuropsychological features but differed in clinical characteristics and vascular mechanisms. Gait disorder (59.1% vs. 0%) and urinary symptoms (77.3% vs. 16.7%) were more common in subcortical dementia than in strategic infarct dementia (P < .05). Small artery disease was most common in subcortical dementia (72.7%). Intracranial large artery disease was associated with all subtypes. The pattern of VaD demonstrated in our study is a reflection of mechanisms of cerebrovascular disease in India. Outcome depends on underlying mechanisms and thus is likely to differ from that in other ethnic populations.",,"Alladi, S.;Kaul, S.;Meena, A. K.;Somayajula, S.;Umadevi, M.;Reddy, J. M.",2006,Mar-Apr,10.1016/j.jstrokecerebrovasdis.2004.09.004,0,
5655,Giant axonal neuropathy: Diffusion-weighted imaging features of the brain,"Giant axonal neuropathy is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Magnetic resonance imaging (MRI) of an 11-year-old boy with giant axonal neuropathy revealed high signal intensity in the white matter of the cerebrum and cerebellum on T(2)-weighted imaging. An apparent diffusion coefficient map revealed increased apparent diffusion coefficient values in the periventricular, deep, and cerebellar white matter, basal ganglia, and thalamus. Increased apparent diffusion coefficient values in distinct locations suggest increased mobility of water molecules in the brain of a patient with giant axonal neuropathy. This finding could indicate a myelin disorder such as demyelination. Diffusion-weighted imaging should be performed to reveal apparent diffusion coefficient changes and determine brain involvement in patients with giant axonal neuropathy.",,"Alkan, A.;Sigirci, A.;Kutlu, R.;Doganay, S.;Erdem, G.;Yakinci, C.",2006,October,,0,
5656,"Global Cerebral Atrophy Detected by Routine Imaging: Relationship with Age, Hippocampal Atrophy, and White Matter Hyperintensities","BACKGROUND AND PURPOSE: Interpreting the clinical significance of moderate-to-severe global cerebral atrophy (GCA) is a conundrum for many clinicians, who visually interpret brain imaging studies in routine clinical practice. GCA may be attributed to normal aging, Alzheimer's disease (AD), or cerebrovascular disease (CVD). Understanding the relationships of GCA with aging, AD, and CVD is important for accurate diagnosis and treatment decisions for cognitive complaints. METHODS: To elucidate the relative associations of age, moderate-to-severe white matter hyperintensities (WMHs), and moderate-to-severe medial temporal lobe atrophy (MTA), with moderate-to-severe GCA, we visually rated clinical brain imaging studies of 325 participants from a community based sample. Logistic regression analysis was conducted to assess the relations of GCA with age, WMH, and MTA. RESULTS: The mean age was 76.2 (+/-9.6) years, 40.6% were male, and the mean educational attainment was 15.1 (+/-3.7) years. Logistic regression results demonstrated that while a 1-year increase in age was associated with GCA (OR = 1.04; P = .04), MTA (OR = 3.7; P < .001), and WMH (OR = 8.80; P < .001) were strongly associated with GCA in our study population. Partial correlation analysis showed that the variance of GCA explained by age is less than the variance attributed to MTA and WMH (r = .13, .21, and .43, respectively). CONCLUSIONS: Moderate-to-severe GCA is most likely to occur in the presence of AD or CVD and should not be solely attributed to age when evaluating clinical imaging findings in the workup of cognitive complaints. Developing optimal diagnostic and treatment strategies for cognitive decline in the setting of GCA requires an understanding of its risk factors in the aging population.",Alzheimer's disease;Global cerebral atrophy;cerebrovascular disease,"Al-Janabi, O. M.;Panuganti, P.;Abner, E. L.;Bahrani, A. A.;Murphy, R.;Bardach, S. H.;Caban-Holt, A.;Nelson, P. T.;Gold, B. T.;Smith, C. D.;Wilcock, D. M.;Jicha, G. A.",2018,Jan 5,,0,
5657,Could a structural damage mimic a Parkinson plus syndrome?,"Corticobasal syndrome (CBS) is a progressive disease that includes a heterogeneous neuropathological spectrum. In the majority of cases, corticobasal degeneration (CBD) is the underlying disease. Clinical heterogeneity is reflected in the clinical presentation of the syndrome and consequently misdiagnosis is common. Our case is of interest because the symptoms, the poor response to L-dopa and the I123 Ioflupane CIT SPECT (DAT-SCAN) results were typical for CBD. However, the magnetic resonance imaging appearance suggested the possibility of a disease of vascular etiology. A 63-year-old woman presented in our outpatient clinic with symptoms of progressive clumsiness in the right arm when performing movements demanding fine motor skills, and mild speech difficulties. The brain magnetic resonance imaging (MRI) report described ischemic lesions in the left subcortical parietal areas, in the centrum semiovale, in periventricular white matter, cingulated gyrus bilaterally and moderate ventricle dilatation. A comprehensive neuropsychological study suggested mixed cortical and subcortical involvement. A DAT-SCAN examination showed a diminished dopamine transporter uptake in the left lenticular nucleus, suggesting parkinsonisn. For this patient, CBS-CBD was the most probable diagnosis, whereas vascular CBS was not excluded. This case report illustrates the low diagnostic sensitivity in predicting CBD and the overlap with other related neurodegenerative diseases. Finally, it demonstrates that in CBS, different underlying pathologies can be found at the same individual. © 2013 Versita Warsaw and Springer-Verlag Berlin Heidelberg.",,"Alexoudi, A.;Zalonis, I.;Stathis, P.",2013,August,,0,
5658,"BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression","OBJECTIVE: The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. METHOD: Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. RESULTS: BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. LIMITATIONS: Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. CONCLUSIONS: Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.","0 (Antidepressive Agents, Second-Generation);0DHU5B8D6V (Citalopram);Aged;Alleles;Antidepressive Agents, Second-Generation;Brain/ pathology;Citalopram/therapeutic use;Corpus Callosum/pathology;Depressive Disorder, Major/drug therapy/ genetics/ pathology;Dominance, Cerebral/physiology;Female;Genetic Carrier Screening;Genotype;Homozygote;Humans;Image Processing, Computer-Assisted;Leukoencephalopathies/ genetics/ pathology;Limbic System/pathology;Magnetic Resonance Imaging;Male;Middle Aged;Neural Pathways/pathology;Polymorphism, Genetic/ genetics;Prognosis;Single-Blind Method;Treatment Outcome","Alexopoulos, G. S.;Glatt, C. E.;Hoptman, M. J.;Kanellopoulos, D.;Murphy, C. F.;Kelly, R. E., Jr.;Morimoto, S. S.;Lim, K. O.;Gunning, F. M.",2010,Sep,,0,
5659,"BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression","OBJECTIVE: The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. METHOD: Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. RESULTS: BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. LIMITATIONS: Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. CONCLUSIONS: Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.","Alleles;Antidepressive Agents, Second-Generation;Brain [pathology];Citalopram [therapeutic use];Corpus Callosum [pathology];Depressive Disorder, Major [drug therapy] [genetics] [pathology];Dominance, Cerebral [physiology];Genotype;Heterozygote Detection;Homozygote;Image Processing, Computer-Assisted;Leukoencephalopathies [genetics] [pathology];Limbic System [pathology];Magnetic Resonance Imaging;Neural Pathways [pathology];Polymorphism, Genetic [genetics];Prognosis;Single-Blind Method;Treatment Outcome;Aged[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword]","Alexopoulos, G. S.;Glatt, C. E.;Hoptman, M. J.;Kanellopoulos, D.;Murphy, C. F.;Kelly, R. E.;Morimoto, S. S.;Lim, K. O.;Gunning, F. M.",2010,,10.1016/j.jad.2010.02.115,0,
5660,CADASIL presenting with a behavioural variant frontotemporal dementia phenotype,"The behavioural variant of frontotemporal dementia (bvFTD) is characterised by personality change with a decline in cognition. We describe two patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) who presented with behavioural phenotypes similar to bvFTD. The first patient presented with progressive personality and behavioural change, had florid white matter hyperintensity, and had a novel missense mutation C366W in exon 7 of the Notch3 gene. The second patient presented with progressive memory impairment and marked personality changes after a transient ischaemic attack. In this second patient, the radiological features were subtle and only the family history of stroke prompted testing for CADASIL using Notch3 genotyping. We present these patients to demonstrate that CADASIL may mimic bvFTD, with little clinical or radiological evidence to distinguish the two. CADASIL may be an under-recognised diagnosis in apparent bvFTD. Screening Notch3 in a substantial and unselected cohort of frontotemporal dementia patients might be appropriate to investigate this possibility. © 2013 Elsevier Ltd. All rights reserved.",Notch3 receptor;adult;aged;amino acid substitution;article;autobiographical memory;behavior change;CADASIL;case report;family history;female;food preference;frontal variant frontotemporal dementia;genetic analysis;genetic screening;genotype;human;memory disorder;middle aged;Mini Mental State Examination;missense mutation;NOTCH3 gene;nuclear magnetic resonance imaging;priority journal;sequence analysis;weight gain,"Alexander, S. K.;Brown, J. M.;Graham, A.;Nestor, P. J.",2014,,,0,
5661,Specific semantic memory loss after hypoxic-ischemic injury,"A patient is reported who suffered hypoxic-ischemic injury causing isolated and eventually partially reversible semantic memory loss. Despite normal MRI findings, single-photon emission CT demonstrated dysfunction in posterior cortical association areas. Semantic memory is the sum of categorical, perceptual, and conceptual knowledge. While not localized in the brain in a strict sense like visual fields, semantic memory is thought to be broadly organized in the posterior association cortices, with a particular focus in the inferior temporal regions. Evidence for this has come from patients with herpes simplex encephalitis, temporo-occipital infarctions, and dementias. This case confirms the importance of these cortical regions for semantic memory. The rapid recovery in this case, as opposed to the encephalitis or infarction cases, suggests an important role for preservation of white matter connections in the region for reconstitution of function.",adult;amnesia;article;association cortex;basal ganglion;brain hypoxia;brain injury;brain ischemia;case report;clinical feature;coma;confusion;heart arrest;heart ventricle fibrillation;human;male;nuclear magnetic resonance imaging;priority journal;seizure;semantics;single photon emission computer tomography,"Alexander, M. P.",1997,,,0,
5662,An Emerging Role for Imaging White Matter in the Preclinical Risk for Alzheimer Disease: Linking beta-Amyloid to Myelin,,,"Alexander, G. E.",2017,Jan 01,,0,
5663,X-linked adrenoleukodystrophy. The Saudi experience,"OBJECTIVE: To evaluate the clinical, biochemical, neuroradiological, and neurophysiological findings of patients with X-linked adrenoleukodystrophy. METHODS: Retrospective study evaluating the data of 10 X-linked adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. RESULTS: The common presenting symptoms were deterioration in school performance, vision and hearing, behavioral changes, and seizures. Eight patients survived 1-4 years and one patient 12 years after the initial presentation, while one patient expired. Six patients had the childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy form. Six are in an advanced stage of the disease and 3 have mild to moderate spasticity. All except 2 manifested moderate to severe dementia with variable degrees of visual loss. Decreased hearing and features of adrenal insufficiency were seen in 7 patients. Very long chain fatty acids were significantly increased in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was increased in all. The characteristic high-signal intensity of parieto-occipital white matter on brain magnetic resonance imaging T2-weighted images was observed in all patients. Two patients had functional study of the brain, which showed hypometabolic activity in gray and white matter of the occipital lobes. Various neurophysiological abnormalities were detected. The response to different treatment modalities was not promising. CONCLUSION: The disease is more common than had been previously recognized due to phenotypic variability and a wide spectrum of presentations. This report describes various aspects of this disorder and emphasizes the importance of early identification and treatment of asymptomatic but biochemically affected individuals, since all current therapeutic approaches are disappointing if overt neurological abnormalities have been already developed.",,"Al-Essa, M. A.;Sakati, N. A.;Bakheet, S. M.;Patay, Z. J.;Dabbagh, O.;Chaves-Carballo, E.;Ozand, P. T.",2000,Jan,,0,
5664,Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment,"Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. Twenty-six HC and 20 older adults with aMCI underwent structural, functional and diffusion MRI scanning using the high angular resolution diffusion-weighted acquisition protocol. The DMN of each subject was identified using independent component analysis (ICA) and resting state effective connectivity was calculated between thalamus and DMN nodes. White matter integrity changes between thalamus and DMN were investigated with constrained spherical deconvolution (CSD) tractography. Significant structural deficits in thalamic white matter projection fibers to posterior DMN components posterior cingulate cortex (PCC) and lateral inferior parietal lobe (IPL) were identified together with significantly reduced effective connectivity from left thalamus to left IPL. Crucially, impaired thalamo-cortical white matter circuitry correlated with memory performance. Disrupted thalamo-cortical structure was accompanied by significant reductions in IPL and PCC cortico-cortical effective connectivity. No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.",Alzheimer's disease;default mode network;diffusion MRI;effective connectivity;mild cognitive impairment;resting state;thalamus;tractography,"Alderson, T.;Kehoe, E.;Maguire, L.;Farrell, D.;Lawlor, B.;Kenny, R. A.;Lyons, D.;Bokde, A. L. W.;Coyle, D.",2017,,,0,
5665,Profiles by sex of brain MRI and cognitive function in the framingham offspring study,"OBJECTIVE: To examine whether there are sex-specific associations between brain magnetic resonance imaging (MRI) measures and neuropsychologic (NP) test performance. BACKGROUND: Differences in cardiovascular risk factors have been linked to decreased total cerebral brain volume and white matter hyperintensities (WMHs). Although brain morphology has been related to cognitive performance, few studies have addressed sex-specific effects in this relationship. METHODS: Framingham Offspring who were stroke and dementia-free underwent a brain MRI scan and NP testing (n=2085; 978 men). Factor analysis identified 4 domain-specific NP factors. MRI participants were divided into 4 MRI subgroups based on measures of total cerebral brain volume and combinations of the presence of WMH and silent cerebral infarcts (> or =3 mm). RESULTS: Overall, the relationship between MRI and NP measures was similar between the sexes. The exception was that only men showed a positive relationship between executive function and cerebrovascular disease defined as large WMH volume plus silent cerebral infarct. This finding was attributed only among men with Framingham Stroke Risk Profile scores >90th percentile range (P=0.0019). CONCLUSIONS: Measures of brain atrophy and subclinical markers of vascular disease showed that sex does not significantly alter the relationship between MRI and NP, except among men and women who are at high risk for stroke; these men show poorer performance on executive function, whereas the women do not.",Brain/ pathology;Cardiovascular Diseases/complications/pathology;Cognition/ physiology;Cognition Disorders/complications/pathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Risk Factors;Sex Characteristics,"Albert, M.;Massaro, J.;DeCarli, C.;Beiser, A.;Seshadri, S.;Wolf, P. A.;Au, R.",2010,Apr-Jun,10.1097/WAD.0b013e3181c1ed44,0,
5666,Overweight and Obesity in Midlife and Brain Structure and Dementia 26 Years Later: The AGES-Reykjavik Study,"High adiposity in midlife might increase risk for late-life brain pathology, including dementia. Using data from the prospective Age, Gene/Environment Susceptibility-Reykjavik Study of men and women (born 1907-1935), we studied the associations of overweight and obesity at midlife (mean age, 50 (standard deviation, 4.7) years) with 1.5-T brain magnetic resonance imaging measures of infarct-like brain lesions, cerebral microbleeds, total brain volume, and white matter lesions volume, as well as dementia, in late life (mean age, 76 (standard deviation, 5.2) years). We used linear and Poisson models to estimate associations in 3,864 persons after adjustment for sociodemographic, health, and lifestyle characteristics. In midlife, the prevalence of overweight was 39% and that of obesity was 8%. After a mean follow-up of 26.2 (standard deviation, 4.9) years, midlife overweight and obesity were not associated with infarct-like brain lesions (relative risk (RR) = 0.82, 95% confidence interval (CI): 0.61, 1.10), cerebral microbleeds (RR = 0.69, 95% CI: 0.37, 1.32), total brain volume (beta = 0.05, 95% CI: -0.34, 0.45), white matter lesions volume (beta = -0.10, 95% CI: -0.20, 0.01), or dementia (RR = 0.91, 95% CI: 0.49, 1.72) compared with normal weight. These findings do not support the hypothesis that high body mass index in midlife modulates the risk for dementia.","Aged;Aged, 80 and over;Body Mass Index;Brain/ pathology;Brain Infarction/ complications;Cerebral Hemorrhage/ complications;Dementia/ etiology/pathology;Female;Follow-Up Studies;Humans;Iceland/epidemiology;Magnetic Resonance Imaging;Male;Middle Aged;Obesity/ complications/mortality/pathology","Albanese, E.;Davis, B.;Jonsson, P. V.;Chang, M.;Aspelund, T.;Garcia, M.;Harris, T.;Gudnason, V.;Launer, L. J.",2015,May 1,10.1093/aje/kwu331,0,
5667,Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease,"Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean +/- SD age 65.1 +/- 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean +/- SD age 64.6 +/- 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean +/- SD age 1532 +/- 138 ms) compared to controls (mean +/- SD age 1335 +/- 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.",Aged;Blood Circulation Time/methods;Cerebral Arteries/ physiopathology;Cerebrovascular Circulation/physiology;Female;Humans;Male;Middle Aged;Parkinson Disease/ diagnosis/ physiopathology;Spin Labels;Time Factors,"Al-Bachari, S.;Parkes, L. M.;Vidyasagar, R.;Hanby, M. F.;Tharaken, V.;Leroi, I.;Emsley, H. C.",2014,,10.1016/j.nicl.2014.07.014,0,
5668,Comparison of quantitative magnetic resonance imaging and positron emission tomography between patients with dementia of the alzheimer type and multi-infarct dementia,,,"Alavi, A.;Newberg, A.;Souder, E.;Reivich, M.",1992,,10.1016/s1052-3057(10)80051-5,0,
5669,Gradually progressive dementia without discrete cerebrovascular events in a patient with Sneddon's syndrome,"A 37-year-old man sought medical advice because of an 8-year history of a slowly progressive dementing illness with no clinically apparent discrete strokelike episodes. Cognitive functioning was markedly, globally impaired without lateralizing or localizing features. Widespread livedo reticularis led to a diagnosis of Sneddon's syndrome. Antiphospholipid antibodies and lupus anticoagulant were negative. Magnetic resonance imaging showed widespread cerebral atrophy, cortical and subcortical cerebral infarcts, and extensive periventricular white matter abnormalities. Cerebral angiography revealed diffuse medium- and small-vessel occlusive disease, with numerous collaterals in the mid and distal circulation but no evidence of atherosclerosis or vasculitis. No other cause of a dementing illness was found. We postulate that our patient's dementia was due to the cumulative effects of multiple cerebral infarcts.",,"Alan Wright, R.;Kokmen, E.",1999,1999,,0,
5670,Diffuse cerebral white matter T2-weighted hyperintensity: a new finding of general paresis,"General paresis (parenchymatous neurosyphilis) is a rare disease, and in recent years the number of papers published on the magnetic resonance imaging findings has been limited. The findings are as follows: cerebral atrophy; mesiotemporal T2 hyperintensity; ventriculomegaly; pathological T2 hypointensity of the globus pallidus, putamen, the head of the caudate nucleus and thalamus. We present a new finding, diffuse cerebral white matter T2 hyperintensity, observed in a patient with general paresis with a 5-year history of progressive dementia.",adult;article;atrophy;brain disease;brain ventricle;case report;caudate nucleus;dementia;frontal lobe;globus pallidus;human;image enhancement;male;methodology;neurosyphilis;nuclear magnetic resonance imaging;parietal lobe;pathology;putamen;temporal lobe;thalamus,"Alam, F.;Yasutomi, H.;Fukuda, H.;Horiguchi, J.;Murakami, Y.;Ohshita, T.;Inoue, K.;Ito, K.",2006,,,0,5671
5671,Diffuse cerebral white matter T2-weighted hyperintensity: a new finding of general paresis,"General paresis (parenchymatous neurosyphilis) is a rare disease, and in recent years the number of papers published on the magnetic resonance imaging findings has been limited. The findings are as follows: cerebral atrophy; mesiotemporal T2 hyperintensity; ventriculomegaly; pathological T2 hypointensity of the globus pallidus, putamen, the head of the caudate nucleus and thalamus. We present a new finding, diffuse cerebral white matter T2 hyperintensity, observed in a patient with general paresis with a 5-year history of progressive dementia.",,"Alam, F.;Yasutomi, H.;Fukuda, H.;Horiguchi, J.;Murakami, Y.;Ohshita, T.;Inoue, K.;Ito, K.",1987,Jul,,0,
5672,The clinical diagnosis of Alzheimer's disease without the use of head imaging studies. A cliniconeuropathological study,"Although head imaging studies are frequently used in the work-up of dementia, published criteria for the clinical diagnosis of Alzheimer's disease (AD) do not require them. Since our brain bank contains cases in which physicians had specifically diagnosed AD without using a head imaging study, we thought it of interest to investigate the accuracy of their clinical diagnoses. We retrospectively reviewed 911 consecutive dementia cases for those clinically diagnosed as either AD or senile dementia (SD). Twenty-one were identified in which head imaging studies had not been used, each diagnosed as AD or SD by a different physician. In only three had the physician reported a reason why a study was not done. In all 21 cases the primary neuropathological cause of the dementia was AD. Neuropathology in addition to AD was also noted, including cortical Lewy bodies in three, infarcts on gross examination in three, multiple microscopic infarcts in four, and multiple cerebral metastases in one. Acknowledging a number of study limitations, it is remarkable that the judgment of the physicians was correct regarding AD in all 21 cases. It is questionable if a head CT or MRI scan at time of diagnosis would have benefited any of the patients.","Aged;Aged, 80 and over;Alzheimer Disease/ diagnosis;Brain/ pathology/ radiography;Female;Humans;Lewy Bodies/pathology;Magnetic Resonance Imaging;Male;Retrospective Studies;Tomography, X-Ray Computed","Ala, T. A.;Mattson, M. D.;Frey, W. H., 2nd",2003,Dec,,0,
5673,Saudi Variant of Multiple Sulfatase Deficiency,"We describe eight patients with multiple sulfatase deficiency (MSD, or Austin's disease) who differ phenotypically from classic neonatal-, childhood-, or juvenile-onset MSD. The age of onset was in childhood. The patients presented with somatic and facial features of mucopolysaccharidosis reminiscent of Maroteaux-Lamy and Morquio syndromes. They differed from classic MSD by the presence of corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus and the absence of ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia. The main neurologic presentation was cervical cord compression due to axis abnormalities. Despite neuroradiologic evidence of white-matter changes, neurologic presentation was not like metachromatic leukodystrophy. The sulfatase deficiencies were more marked than in the classic juvenile form of MSD, but less marked than in the classic childhood-onset form of MSD. Steroid sulfatase activity was spared except in one patient. This Saudi variant of MSD accounts for 5% of all lysosomal storage diseases in the Cell Repository Registry of our Inborn Errors of Metabolism Laboratory.",article;central hearing loss;cervical spinal cord injury;child;computer assisted tomography;dementia;enzyme activity;female;functional magnetic resonance imaging;human;Hurler syndrome;hydrocephalus;ichthyosis;macrocephaly;male;Maroteaux Lamy syndrome;mental deficiency;metachromatic leukodystrophy;Morquio syndrome;mucopolysaccharidosis;multiple sulfatase deficiency;preschool child;priority journal;retina degeneration;Saudi;school child,"Al Aqeel, A.;Ozand, P. T.;Brismar, J.;Gascon, G. G.;Brismar, G.;Nester, M.;Sakati, N.",1992,,10.1177/08830738920070010311,0,
5674,Association of Cerebral Microbleeds With Cognitive Decline and Dementia,"IMPORTANCE: Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear. OBJECTIVE: To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population. DESIGN, SETTING, AND PARTICIPANTS: The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards. EXPOSURES: Cerebral microbleed presence, location, and number. MAIN OUTCOMES AND MEASURES: Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia. RESULTS: In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64). CONCLUSIONS AND RELEVANCE: In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.",,"Akoudad, S.;Wolters, F. J.;Viswanathan, A.;de Bruijn, R. F.;van der Lugt, A.;Hofman, A.;Koudstaal, P. J.;Ikram, M. A.;Vernooij, M. W.",2016,Aug 1,10.1001/jamaneurol.2016.1017,1,
5675,Cerebral microbleeds and the risk of mortality in the general population,"Presence of cerebral microbleeds indicates underlying vascular brain disease and has been implicated in lobar hemorrhages and dementia. However, it remains unknown whether microbleeds also reflect more systemic vascular burden. We investigated the association of microbleeds with all-cause and cardiovascular related mortality in the general population. We rated the brain magnetic resonance imaging scans of 3979 Rotterdam Scan Study participants to determine presence, number, and location of microbleeds. Cox proportional hazards models, adjusted for age, sex, subcohort, vascular risk factors, and other MRI markers of cerebral vascular disease, were applied to quantify the association of microbleeds with mortality. After a mean follow up of 5.2 (±1.1) years, 172 (4.3 %) people had died. Presence of microbleeds, and particularly deep or infratentorial microbleeds, was significantly associated with an increased risk of all-cause mortality [sex-, age-, subcohort adjusted hazard ratio (HR) 2.27; CI 1.50-3.45], independent of vascular risk factors (HR 1.87; 95 % CI 1.20-2.92). The presence of deep or infratentorial microbleeds strongly associated with the risk of cardiovascular related mortality (HR 4.08; CI 1.78-9.39). Mortality risk increased with increasing number of microbleeds. The presence of microbleeds, particularly multiple microbleeds and those in deep or infratentorial regions, indicates an increased risk of mortality, independent of other MRI markers of cerebral vascular disease. Our data suggest that microbleeds may mark severe underlying vascular pathology associated with poorer survival. © 2013 Springer Science+Business Media Dordrecht.",,"Akoudad, S.;Ikram, M. A.;Koudstaal, P. J.;Hofman, A.;Van Der Lugt, A.;Vernooij, M. W.",2013,October,,0,
5676,Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes intervention trial (J-EDIT),"BACKGROUND: Type 2 diabetes is associated with cognitive dysfunction and increases the risk of dementia in the elderly. The aim of this study was to explore, by means of magnetic resonance (MR) imaging, possible relationships among clinical profiles of diabetes, cognitive function, white matter hyperintensities (WMHs) and subcortical brain atrophy. METHODS: Data were obtained from 95 nondemented type 2 diabetic participants aged 65 years or over, enrolled in an intervention trial for Japanese elderly diabetic patients. Cognitive function was measured with neuropsychiatric tests, including mini-mental state examination (MMSE), verbal memory, digit symbol substitution and Stroop tests. Hyperintensity was classified into periventricular, deep white matter, thalamic and basal ganglia. Four ventricle-to-brain ratios were used to measure subcortical atrophy. To identify clinical features of diabetes, indices of glycemic control, lipid metabolism, blood pressure and complications were examined. Canonical correlation analysis and regression analysis were used to assess correlation. RESULTS: Scores for digit symbol substitution and MMSE negatively correlated with WMHs in the parietal lobe and hyperintensities in the thalamus, respectively. Lower scores for memory and digit symbol substitution showed positive association with enlarged subcortical atrophy adjacent to lateral ventricles. There was no association between clinical pictures of diabetic patients with cognitive dysfunction and of those with morphological changes in the brain. CONCLUSIONS: Impaired cognitive domains of the speed of mental processes and memory were associated with WMHs and subcortical atrophy. Degenerative changes in the cerebral small vessels may constitute predictive factors for the rate of cognitive dysfunction in elderly diabetic patients.","Aged;Atrophy;Body Mass Index;Brain/ pathology;Cognition Disorders/ epidemiology;Diabetes Mellitus, Type 2/blood/physiopathology/ psychology;Female;Humans;Informed Consent;Japan;Magnetic Resonance Imaging;Male;Socioeconomic Factors","Akisaki, T.;Sakurai, T.;Takata, T.;Umegaki, H.;Araki, A.;Mizuno, S.;Tanaka, S.;Ohashi, Y.;Iguchi, A.;Yokono, K.;Ito, H.",2006,Sep-Oct,10.1002/dmrr.632,0,
5677,Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age,"Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families (""offspring"") and controls; and age categories thereof. From the Leiden Longevity Study (LLS), 132 participants underwent an oral glucose tolerance test (OGTT) to assess glycemia [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR) peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age. In the full offspring group only, reduced MTR peak-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p < 0.01). When dichotomized for age (</=65 years and >65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction < 0.05). Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.",,"Akintola, A. A.;van den Berg, A.;van Buchem, M. A.;Jansen, S. W.;Slagboom, E. P.;Westendorp, R. G.;van der Grond, J.;van Heemst, D.",2015,,10.3389/fnagi.2015.00092,0,
5678,Alterations in glia and axons in the brains of Binswanger's disease patients,"BACKGROUND AND PURPOSE: Although increasing attention is being paid to Binswanger's disease, a form of vascular dementia characterized by diffuse white matter lesions, only limited information is available on the pathological changes that occur in the glia and axons in the white matter. We therefore investigated the brains of patients with Binswanger's disease to gain further insight into its pathophysiology. METHODS: Autopsied brains from patients with Binswanger's disease (group 3; n = 17) were compared with those of nonneurological controls (group 1; n = 5) and controls with large cortical infarcts but without significant white matter lesions (group 2; n = 5). Glial fibrillary acidic protein (GFAP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR was used as a marker for activated microglia. Axonal damage was assessed by the accumulation of proteins, which are transported by fast axonal flow, amyloid protein precursor (APP), synaptophysin, and chromogranin A. RESULTS: Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia were observed in 7 of 17 patients with Binswanger's disease. LCA-immunoreactive microglia were 1.7 times more numerous in Binswanger's disease than in group 1 (P < .05). HLA-DR-immunoreactive-activated microglia were 3.4 times and 2.1 times more numerous in Binswanger's disease as compared with group 1 (P < .01) and group 2 (P < .05), respectively. There was frequent perivascular lymphocyte cuffing, and clusters of macrophages with a decreased number of oligodendroglia were observed in the rarefied white matter. The grading scores for the number of axons immunoreactive for either APP, synaptophysin, or chromogranin A were significantly higher in Binswanger's disease than in group 1 or 2. CONCLUSIONS: The pathological alterations in Binswanger's diseased brains include regressive changes in the astroglia and activation of the microglia with a decrease in the oligodendroglia, which were associated with the degradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, mediated by chronic ischemia, may play an important role in the pathophysiology of Binswanger's disease.","Aged;Aged, 80 and over;Amyloid beta-Protein Precursor/analysis/immunology;Antibody Specificity;Astrocytes/*pathology;Axons/*pathology;Brain/*pathology;Brain Chemistry;Brain Ischemia/diagnosis/pathology;Chromogranin A;Chromogranins/analysis/immunology;Dementia, Vascular/diagnosis/*pathology;Female;Humans;Immunohistochemistry;Magnetic Resonance Imaging;Male;Microglia/*pathology;Middle Aged;Synaptophysin/analysis/immunology","Akiguchi, I.;Tomimoto, H.;Suenaga, T.;Wakita, H.;Budka, H.",1997,Jul,,0,
5679,Disproportionate subarachnoid space hydrocephalus—outcome and perivascular space,"Objective: We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH-iNPH) and to describe the clinico-radiological features and outcomes of a community-based investigation (The Vienna Trans-Danube Aging study). Methods: Of the 697 inhabitants (all 75 years old), 503 completed extensive neurological examinations at baseline and were followed up every 30 months thereafter with MRIs, mini-mental state examination (MMSE), and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). The DESH-iNPH participant data were compared with the data from participants with Evans index ratios >0.3 (ex vacuo hydrocephalus), cerebral small-vessel diseases, and normal MRIs. The widening of perivascular space was also evaluated by MRI in these groups. Results: Eight participants with DESH-iNPH (1.6%) and 76 with ex vacuo hydrocephalus (16.1%) at baseline were identified. The mean MMSE in DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs was 26.4, 27.9, and 28.3, respectively, and the mean UPDRSM was 9.75, 2.96, and 1.87, respectively. After a 90-month follow-up, the mortality rates for DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs were 25.0%, 21.3%, and 10.9%, respectively. The perivascular-space widening scores were significantly smaller in the DESH-iNPH cases, particularly at the centrum semiovale, compared to cerebral small-vessel disease and ex vacuo hydrocephalus cases. Interpretation: The prevalence of DESH-iNPH was 1.6% for participants aged 75 years and revealed significantly lower MMSE and higher UPDRSM scores compared to the ex vacuo hydrocephalus and controls. Moreover, it is suggested that perivascular-space narrowing is a morphological and pathophysiological marker of DESH-iNPH.",Alzheimer disease;article;Binswanger encephalopathy;cohort analysis;female;functional neuroimaging;human;hydrocephalus;major clinical study;male;mortality rate;neurologic examination;normotensive hydrocephalus;perivascular space;prevalence;priority journal;prospective study;subarachnoid space;trail making test,"Akiguchi, I.;Shirakashi, Y.;Budka, H.;Watanabe, Y.;Watanabe, T.;Shiino, A.;Ogita, M.;Kawamoto, Y.;Jungwirth, S.;Krampla, W.;Fischer, P.",2014,,10.1002/acn3.87,0,
5680,Shunt-responsive parkinsonism and reversible white matter lesions in patients with idiopathic NPH,"BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a potentially treatable dementia and gait disorder with abnormal CSF dynamics. OBJECTIVE: To investigate and characterize the changes in motor symptoms and CT and MRI features of iNPH before and after a shunt operation using specific evaluation criteria. METHODS: We studied 17 definitive iNPH patients, diagnosed according to the clinical guidelines of both the Japanese Society of NPH and the International NPH Consultant Group, with ventricular enlargement (Evan's index > 0.3) and narrowed CSF spaces at the high convexity on CT scan and /or MRI. The pre- and post-operative evaluation criteria for the gait and motor disturbances included the Japanese NPH Grading Scale-Revised (JNPHGSR), the Timed ""Up and Go"" test and the motor sections of the Unified Parkinson Disease Rating Scale. For cognitive impairments, the JNPHGSR, Mini Mental State Examination, Frontal Assessment Battery and Trail Making Test were used. White matter lesions were rated from the CT and/or MRI using a validated visual rating scale. RESULTS: All patients showed specific CT and MRI findings, consisting of diffusely-dilated Sylvian fissure, as well as narrowed CSF space at the high convexity. Fifteen patients (88%) showed white matter lesions on their CT or MRI images. These signs were ameliorated in all patients after the shunt operation. Evan's index and the mean total scores on the visual scale for white matter lesions also improved significantly. Clinically, the patients had frequent parkinsonism (71%), but relatively few had a history of either small-vessel diseases (29%), hypertension (41%) or diabetes (35%). All patients showed gait disturbances, and these symptoms, including postural instability and body bradykinesia, improved significantly after the operation. Over half also showed signs of cognitive impairment and urinary incontinence, and all such symptoms and signs improved significantly. CONCLUSION: iNPH often appears as a shunt-responsive type of parkinsonism and reversible white matter lesions among the geriatric population.","Aged;Aged, 80 and over;Brain/pathology/physiopathology/ surgery;Cerebrospinal Fluid Pressure/physiology;Cerebrospinal Fluid Shunts/ methods;Cognition Disorders/diagnosis/etiology;Female;Gait Disorders, Neurologic/diagnosis/etiology;Humans;Hydrocephalus, Normal Pressure/complications/physiopathology/ surgery;Magnetic Resonance Imaging/methods;Male;Neuropsychological Tests/statistics & numerical data;Parkinsonian Disorders/etiology/ physiopathology;Recovery of Function;Tomography, X-Ray Computed/methods;Urinary Incontinence/diagnosis/etiology","Akiguchi, I.;Ishii, M.;Watanabe, Y.;Watanabe, T.;Kawasaki, T.;Yagi, H.;Shiino, A.;Shirakashi, Y.;Kawamoto, Y.",2008,Sep,10.1007/s00415-008-0928-1,0,
5681,MRI features of Binswanger's disease predict prognosis and associated pathology,"OBJECTIVE: To identify the prevalence of MRI features of Binswanger's disease (BD), specifically MRI with diffuse white matter lesions and scattered multiple lacunes (BD-MRI), and to describe neurological features and pathological outcomes of a community-based cohort study. METHODS: Of 697 participants (all 75 years old), 503 completed neurological examinations at baseline and were followed-up every 30 months thereafter with MRIs, the mini-mental state examination (MMSE) and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). Data from participants with BD-MRI were compared with those from participants with predominant white matter lesions (WML-MRI), scattered multiple lacunes (ML-MRI), or normal MRIs. RESULTS: Fourteen BD-MRI patients (2.8%) were detected at baseline. The mean MMSE scores in the BD-MRI, WML-MRI, ML-MRI, and normal MRIs groups were 26.4, 28.2, 28.4, and 28.5, respectively, and the mean UPDRSM scores were 9.1, 1.3, 3.1, and 1.7, respectively. At the 30-month follow-up, mortality rates in the normal MRIs, WML-MRI and ML-MRI were 4%, 9.1%, and 22.2%, respectively, and follow-up MRIs were available for 80%, 82%, and 61% of the participants, respectively. In the BD-MRI, however, five patients were deceased, and only five follow-up individual MRIs were available (33.3%). Autopsies were performed on six of eight BD-MRI brains, and these brains fulfilled the pathological criteria for BD independent of Alzheimer disease pathology. All these six individuals also showed systemic atherosclerosis and renal arterio-arteriolosclerosis. INTERPRETATION: The BD-MRI participants had poor prognoses and showed pure BD pathology with advanced systemic vascular disease. BD-MRI appears to be a predictor of vascular neurocognitive impairment.",,"Akiguchi, I.;Budka, H.;Shirakashi, Y.;Woehrer, A.;Watanabe, T.;Shiino, A.;Yamamoto, Y.;Kawamoto, Y.;Krampla, W.;Jungwirth, S.;Fischer, P.",2014,Oct,10.1002/acn3.123,0,
5682,Acute-onset dementia with right homonymous hemianopsia. A syndrome of posterior cerebral artery territory infarction on the dominant side,"It is well known that medial temporal lobe infarcts including the hippocampus cause amnesia. However, no computed tomography (CT) study of this problem has been done. The authors selected thirty-four patients with hemianopsia and CT evidence of infarction in the unilateral posterior cerebral artery territory. The correlation between neurologic findings and CT distribution of infarction in these patients showed that dementia syndrome, ranging from recent memory loss to severe permanent memory disturbance with other psychoneurologic symptoms, was more common in patients with left hemisphere lesions. Moreover, there were high incidences of memory disturbance when infarcts in the left posterior cerebral artery territory involved the medial portion of the temporal lobe. Memory disturbance was found in 12 out of 20 patients (60%) with lesions on the dominant, but in only 3 out of 14 (21.4%) on the non-dominant side. It is important to be aware that 'acute-onset dementia with right homonymous hermianopsia' can follow ischemic lesions in the territory of the posterior cerebral artery on the dominant side.",central nervous system;cerebrovascular disease;computer analysis;computer assisted tomography;dementia;diagnosis;etiology;hemianopia;major clinical study;peripheral vascular system;posterior cerebral artery,"Akiguchi, I.;Aii, H.;Kameyama, M.",1981,,,0,
5683,Adaptive metabolic changes in CADASIL white matter,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using (1)H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. (1)H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T (E) = 288 ms) and non-accelerated medium-resolution MRSI (T (E) = 35 ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre/Cho, Glx/Cho and Glx/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx/Cre and mI/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx/Cre and mI/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia.","Adult;Aged;Brain/ metabolism;CADASIL/genetics/ metabolism;Female;Humans;Magnetic Resonance Imaging;Magnetic Resonance Spectroscopy/methods;Male;Middle Aged;Mutation, Missense;Nerve Fibers, Myelinated/ metabolism;Protons;Receptors, Notch/genetics;Severity of Illness Index","Akhvlediani, T.;Henning, A.;Sandor, P. S.;Boesiger, P.;Jung, H. H.",2010,Feb,10.1007/s00415-009-5281-5,0,
5684,Optimization of image reconstruction conditions with phantoms for brain FDG and amyloid PET imaging,"OBJECTIVES: The purpose of this study was to optimize image reconstruction conditions for brain (18)F-FDG, (11)C-PiB, (18)F-florbetapir and (18)F-flutemetamol PET imaging with Discovery-690 PET/CT for diagnosis and research on Alzheimer's disease (AD) based on the standard imaging protocols and phantom test procedures and criteria published by the Japanese society of nuclear medicine (JSNM). METHODS: A Hoffman 3D brain phantom and a cylindrical pool phantom were scanned according to the JSNM procedure, and the reconstruction conditions (iteration, subset, post-filter) were optimized so that the images satisfy the JSNM criteria regarding spatial resolution (FWHM </= 8 mm) and gray/white matter contrast (%contrast >/= 55%) on the Hoffman phantom and uniformity (SD of small ROIs </= 0.0249) and image noise (coefficient of variation </= 15 %) on the pool phantom. Human images were acquired with (18)F-FDG (15-min scan starting at 30 min post-injection [p.i.] of 185 MBq), (11)C-PiB (20-min scan starting at 50 min p.i. of 555 MBq), (18)F-florbetapir (10-min scan starting at 50 min p.i. of 370 MBq) and (18)F-flutemetamol (30-min scan starting at 90 min p.i. of 185 MBq) on 1 or 2 subjects for each tracer and reconstructed with thus determined conditions to evaluate the image quality visually. The effect of reconstruction parameters on the standardized uptake value ratio (SUVR) was also evaluated on 5 amyloid-positive and 5 amyloid-negative PiB images. RESULTS: A sufficient image quality was obtained at an iterative update (product of iteration and subset) of 64 for (18)F-FDG. The same reconstruction parameters with an additional Gaussian filter of 5 mm FWHM was optimal for (11)C-PiB, (18)F-florbetapir and (18)F-flutemetamol to achieve the phantom criteria. Those optimal reconstruction conditions were confirmed with human images. The SUVR value was stable over a wide range of iterative updates around the optimal parameters both for positive and negative amyloid images. CONCLUSIONS: Optimal image reconstruction conditions were determined for brain (18)F-FDG and amyloid PET imaging with Discovery-690 PET/CT for diagnosis and research on AD based on the JSNM phantom criteria. This supports feasibility of the phantom criteria for standardization and harmonization of brain (18)F-FDG and amyloid PET for multicenter studies.",,"Akamatsu, G.;Ikari, Y.;Nishio, T.;Nishida, H.;Ohnishi, A.;Aita, K.;Sasaki, M.;Senda, M.",2016,Jan,10.1007/s12149-015-1024-0,0,
5685,Different strategies for auditory word recognition in healthy versus normal aging,"To explore the effects of commonly encountered pathology on auditory recognition strategies in elderly participants, magnetoencephalographic (MEG) brain activation patterns and performance were examined in 30 elderly [18 controls and 12 elderly with mild cognitive impairment (MCI) or probable Alzheimer's disease (AD)]. It was predicted that participants with known pathology would reveal different networks of brain activation, compared to healthy elderly, which should correlate with poorer performance. Participants heard a list of words representing common objects, twice. After 20 minutes a list of new and old words was presented and participants judged whether each word was heard earlier. MEG responses were analyzed using a semiautomated source modeling procedure. A cluster analysis using all subjects' MEG sources revealed three dominant patterns of activity which correlated with IQ and task performance. The highest performing group revealed activity in premotor, anterior temporal, and superior parietal lobes with little contribution from prefrontal cortex. Performance and brain activation patterns were also compared for individuals with or without abnormalities such as white matter hyperintensities and/or volume reduction evidenced on their MRIs. Memory performance and activation patterns for individuals with white matter hyperintensities resembled the group of MCI/AD patients. These results emphasize the following: (1) general pathology correlates with cognitive decline and (2) full characterization of the health of elderly participants is important in studies of normal aging since random samples from the elderly population are apt to include individuals with subclinical pathology that can affect cognitive performance. © 2009 Elsevier Inc.",adult;aged;aging;Alzheimer disease;article;auditory discrimination;brain mapping;clinical article;cognitive defect;controlled study;female;geriatric patient;human;intelligence quotient;magnetoencephalography;male;mild cognitive impairment;nuclear magnetic resonance imaging;parietal lobe;prefrontal cortex;premotor cortex;priority journal;task performance;temporal cortex;white matter;word recognition,"Aine, C. J.;Bryant, J. E.;Knoefel, J. E.;Adair, J. C.;Hart, B.;Donahue, C. H.;Montaño, R.;Hayek, R.;Qualls, C.;Ranken, D.;Stephen, J. M.",2010,,,0,
5686,Extracranial disseminations,"An autopsy case of malignant lymphoma of the central nervous system which showed extracranial disseminations was presented. A 50-year-old man developed mental and physical slowness over one year prior to admission followed by dementia and consciousness disturbance without general physical symptoms. Physical examination on admission showed no lymph node enlargement, hepatomegaly, splenomegaly, or abdominal mass. Neurological examination revealed mild dementia, left positive Babinski and Chaddock reflexes, and bilateral positive frontal lobe signs. CT scan revealed low densitry areas with contrast enhancement in the white matter of the bilateral parietal lobes adjacent to the trigon of lateral ventricles. Without any therapy, the low density area in the left cerebral hemisphere on CT scan disappeared and the low density area in the right cerebral hemisphere became unenhanced. Any other lesions except brain were found despite of the extensive systemic examinations including schintigrams, echograms, gastrointestinal examinations, body CT scan, aspiration of bone marrow, and lymphography. Prymary intracranial malignant lymphoma was suspected and treated with steroid without any response. Subsequent radiation therapy made a transient improvement. But a few months later, the brain lesions gradually worsened, followed by general physical deterioration with diarrhea, pleural fluids, and ascites. Cytologic study of cerebrospinal fluid revealed neoplastic lymphocytes with atypical nuclei containing conspicuous nucleoli and mitosis, which were identified as B cell type malignant lymphoma by analysis using monoclonal antibody. The patient died of cardiac failure about two years after the initial symptom. The autopsy disclosed malignant lymphoma (diffuse lymphoma, large cell type, non cleaved, B cell type) of the brain with extracranial spreading, involving lungs, liver, kidneys, adrenal glands, and submucosal regions of esophagus, stomach, and small intestine. Extensive tumor growth was noted in the retroperitoneal lymph nodes. The bone marrow or the spleen was not involved. Considering the clinical course, systemic examinations and autopsy findings, this case was probably a primary intracranial malignant lymphoma with extracranial involvement. A primary intracranial malignant lymphoma with dissemination to extracranial regions has not been well documented in the past. Clinical presentation of only mental disturbance over one year without focal neurological symptoms and increased intracranial pressure, and CT scan findings of the low density area without contrast enhancement effect in the course of this case were of rare occurrence and interesting. The importance of cerebrospinal fluid cell analysis using monoclonal antibody to detect B cell type lymphoma was also to be stressed.",monoclonal antibody;adult;article;brain lymphoma;case report;computer analysis;computer assisted tomography;human;male;metastasis,"Aimoto, Y.;Ogata, A.;Fukazawa, T.;Tashiro, K.;Nagashima, K.",1990,,,0,
5687,Calcification of basal ganglia on computed tomography,"A review of CT scans in 5962 consecutive patients revealed high density foci indicating calcification in the basal ganglia in 90 patients (1.6%). 6 Patients with incomplete clinical data were excluded, and the remaining 84 patients were divided into 3 groups. Group A was comprised of 15 patients with conditions known to have calcification in the basal ganglia. Clinical diagnosis in this group was hypoparathyroid disease in 5, postirradition in 8, and idiopathic brain calcification (Fahr's disease) in the remaining 2. In group B, clinical conditions in 5 patients were thought to have some relation, though not yet established, with calcification of the basal ganglia. One patient with Werner's syndrome, myotonic dystrophy and spinocerebellar degeneration, and 2 children with mental retardation belonged to this group. In 64 patients in group C, calcification in the basal ganglia was thought to be purely incidental. Clinical diagnosis in this group was cerebrovascular accident (CVA) in 17, brain tumor in 17, headache in 9, dementia of psychosis in 7, and miscellaneous in the remaining 14. 61 Out of the 64 patients were 41 yr of age or older. 2 Patients showed extrapyramidal symptoms and signs, but the calcification in both patients seemed to be unrelated to their symptomatology. Nonspecific, incidental calcification in group C was characteristically confined to a focal area of the globus pallidus. This CT finding seems to conform well with the previous pathologic reports in which the oral part of the globus pallidus has been described as the site of predilection of non-specific microscopic calcification in the elderly. Attenuation of the dense focus in this group exceeded that of the normal brain in 13 to 40 in CT number. In comparison, computed tomographic calcification in patients with severe hypoparathyroid disease involved the head of the caudate nucleus, putamen, dentate nucleus, cerebral cortex and cerebral white matter, in addition to the globus pallidus, and the attentuation within the focus was much higher than that of group C. In patients with post-irradiation the location of the computed tomographic calcification was essentially similar to that in group C, but in some cases high density was noted diffusely in the basal ganglia. In group B, patients presented with protean neurologic symptoms and signs, such as extrapyramidal manifestations, convulsive seizures, various EEG abnormalities, and mental retardation. In 2 children with mental retardation, calcification was noted also in the deep white matter. Cataracts are often seen not only in hypoparathyroid disease but also in Werner's syndrome and myotonic dystrophy, and the patient with spinocerebellar degeneration in this series also showed cataracts. In this group, the presence of some unidentified metabolic disorders is probable. In conclusion, the possibility of specific disease showing calcification in the basal ganglia should be seriously considered in the following circumstances: when calcification in the basal ganglia is found in patients aged 40 or younger, when attenuation of the dense focus exceeds that of the normal brain by more than 40 in CT number, or when calcification involves caudate nucleus, putamen, dentate nucleus, cerebral cortex or cerebral white matter.",central nervous system;computer analysis;computer assisted tomography;diagnosis;Fahr disease;major clinical study;peripheral vascular system,"Aii, H.;Kameyama, M.;Nakano, Y.;Handa, J.",1980,,,0,
5688,Impact of regional white matter lesions on cognitive function in subcortical vascular cognitive impairment,"OBJECTIVES: Exact characterization and localization of white matter lesions (WMLs) as they relate and contribute to vascular cognitive impairment is highly debated. The purpose of this study was to investigate the impact of WML on cognitive function by using a new anatomy-based classification method. METHODS: We detected WML accurately by using a three-dimensional fluid-attenuated inversion recovery (3D FLAIR) imaging technique and subsequently segmented WMLs by using an anatomy-based method. Participants included 56 consecutive patients diagnosed with subcortical vascular cognitive impairment (SubVCI). The volume of WMLs in different anatomic regions was measured. The volume of the hippocampus, the corpus callosum (CC), any lacunar infarcts, total gray matter (GM), and total brain volumes were also calculated. RESULTS: Hippocampal (P = 0.005) as well as temporal WML volumes (P = 0.039) were both independently associated with mini-mental state examination (MMSE) score. Only the parietal WML volume (P = 0.000) was independently associated with Montreal Cognitive Assessment (MoCA) score. Frontal WMLs were independently correlated with executive function. Occipital WMLs were independently associated with visuospatial and recall function. Language impairment was independently correlated with both parietal GM and parietal WML volume. Functions related to orientation were independently associated with parietal WML volume. DISCUSSION: The volume of WMLs in the temporal region as well as in the hippocampus were both independently associated with MMSE score. For the MoCA score, however, only parietal WML volumes were independently correlated. White matter lesions within different anatomic regions were separately correlated with different subdomains of cognitive function.","Aged;Brain/ pathology;Cerebrovascular Disorders/ pathology/psychology;Cognition;Cognition Disorders/ pathology/psychology;Female;Hippocampus/pathology;Humans;Imaging, Three-Dimensional;Magnetic Resonance Imaging;Male;Middle Aged;Neuropsychological Tests;Organ Size;Temporal Lobe/pathology;White Matter/ pathology","Ai, Q.;Pu, Y. H.;Sy, C.;Liu, L. P.;Gao, P. Y.",2014,May,10.1179/1743132814y.0000000354,0,
5689,Vascular dementia in patients with immune thrombocytopenic purpura,"INTRODUCTION: Platelets have been implicated in memory disorders but this has not been investigated in patients with immune or idiopathic thrombocytopenia (ITP). ITP is an autoimmune disorder in which autoantibodies bring about platelet destruction. We previously reported a group of ITP patients who manifested TIA-like syndrome and gradual memory loss leading to dementia: platelet microparticles (PMP), a marker of platelet activation, were often elevated, suggesting that procoagulant PMP released from stimulated platelets contributed to thrombosis in small vessels. We have expanded on those studies to better define the clinical, laboratory, and radiologic characteristics of this syndrome. MATERIALS AND METHODS: Twenty ITP patients with this syndrome were studied in comparison to twenty-three ITP patients without it (patient controls). Clinical and laboratory features were compared and radiologic images were analyzed. Factors influencing the rate of progression to advanced dementia were also investigated. RESULTS AND CONCLUSION: Recurring dizzy or weak spells, TIA-like syndrome, recent memory loss, and cognitive impairment were common initial complaints. In some, these symptoms progressed rapidly to dementia but was indolent in others. Progression was faster in those with splenectomy and higher platelet counts. MRI showed enhanced signal in subcortical, periventricular areas, consistent with ischemic small vessel disease. Compared to patient controls, bleeding was less frequent and platelet activation (increased PMP, CD62p) was more frequent in the study group. Thrombotic complications may occur in ITP, manifested as TIA-like syndrome or memory loss due to ischemic small vessel disease, progressing to vascular dementia. Memory disturbances associated with platelet disorders warrants further investigation.","Adult;Aged;Chi-Square Distribution;Dementia, Vascular/diagnosis/ etiology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Purpura, Thrombocytopenic, Idiopathic/classification/ complications;Severity of Illness Index;Statistics, Nonparametric;Syndrome","Ahn, Y. S.;Horstman, L. L.;Jy, W.;Jimenez, J. J.;Bowen, B.",2002,Sep 15,,0,
5690,White matter hyperintensities in subjects with bipolar disorder,"There have been divergent reports on the prevalence and severity of white matter hyperintensities (WMH) on brain magnetic resonance (MR) images in subjects with bipolar disorder. In the present study, evaluations were made on the prevalence and severity of WMH in subjects with bipolar disorder using contiguous 3-mm thick MR slices as well as fluid attenuated inversion recovery (FLAIR) images. A detailed WMH rating system was employed to assess these WMH. A total of 43 bipolar patients, as diagnosed by the Structured Clinical Interview from the Diagnostic and Statistical Manual-IV (SCID-IV), and 39 healthy comparison subjects were scanned using a 1.5-T whole body GE magnetic resonance scanner. WMH were assessed with a modified composite version of the Fazekas' and Coffey's rating scales to detect less severe WMH. Periventricular and subcortical WMH were coded separately. Subjects with bipolar disorder had greater prevalence of WMH abnormalities than comparison subjects (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%, grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This difference is mainly due to the differences in deep WMH (Bipolar, grade 1 = 14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). The current study confirms the higher prevalence of WMH in subjects with bipolar disorder. Differences of small-sized WMH abnormalities between groups were successfully detected using a large number of bipolar subjects and thinner sliced MR images with FLAIR.","Adult;Bipolar Disorder/ diagnosis/psychology;Brain/ pathology;Cerebral Ventricles/pathology;Dementia, Vascular/ diagnosis/psychology;Female;Humans;Image Enhancement;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Nerve Fibers, Myelinated/pathology;Reference Values","Ahn, K. H.;Lyoo, I. K.;Lee, H. K.;Song, I. C.;Oh, J. S.;Hwang, J.;Kwon, J.;Kim, M. J.;Kim, M.;Renshaw, P. F.",2004,Oct,10.1111/j.1440-1819.2004.01294.x,0,
5691,Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics,"The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [(18)F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.",,"Ahn, H. J.;Yoo, W. K.;Park, J.;Ma, H. I.;Kim, Y. J.",2015,Sep,10.3346/jkms.2015.30.9.1328,0,
5692,Globular glial tauopathies (GGT): consensus recommendations,"Recent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunoreactive globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and corticospinal tract being severely affected. Extrapyramidal features can be present in Type II and III cases and significant degeneration of the white matter is a feature of all GGT subtypes. Improved detection and classification will be necessary for the establishment of neuropathological and clinical diagnostic research criteria in the future.",Astrocytes/pathology;Consensus;Humans;Immunohistochemistry;Inclusion Bodies/pathology;Neurodegenerative Diseases/pathology;Neuroglia/ pathology;Silver Staining;Tauopathies/classification/ pathology;Terminology as Topic;tau Proteins/chemistry,"Ahmed, Z.;Bigio, E. H.;Budka, H.;Dickson, D. W.;Ferrer, I.;Ghetti, B.;Giaccone, G.;Hatanpaa, K. J.;Holton, J. L.;Josephs, K. A.;Powers, J.;Spina, S.;Takahashi, H.;White, C. L., 3rd;Revesz, T.;Kovacs, G. G.",2013,Oct,10.1007/s00401-013-1171-0,0,
5693,A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids,"We report a family with a novel CSF1R mutation causing hereditary diffuse leucoencephalopathy with axonal spheroids. Family members presented with neuropsychiatric and behavioural symptoms, with subsequent development of motor symptoms and gait disturbance. MRI brain showed extensive white matter change with a frontal predominance and associated atrophy in two members of the family. Genetic testing revealed a novel mutation c.2342C>T (p.A781V) in the CSF1R gene in two brothers of the family. This report highlights the difficulties in diagnosing HDLS and discusses the indications for testing for mutations in the CSF1R gene.","Aged;Alanine/*genetics;Family Health;Female;Fluorodeoxyglucose F18;Genetic Testing;Humans;Leukoencephalopathies/genetics;Magnetic Resonance Imaging;Male;Middle Aged;Mutation/*genetics;Positron-Emission Tomography;Receptor, Macrophage Colony-Stimulating Factor/*genetics;Valine/*genetics;Behavioural change;Csf1r;Dementia;Frontal dementia;Hdls;Leucoencephalopathy","Ahmed, R.;Guerreiro, R.;Rohrer, J. D.;Guven, G.;Rossor, M. N.;Hardy, J.;Fox, N. C.",2013,Sep 15,10.1016/j.jns.2013.06.007,0,
5694,Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study,"OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). METHODS: The setting of the study was at the Alzheimer Center Reina Sofia Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. RESULTS: Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 +/- 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected). CONCLUSIONS: Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright (c) 2016 John Wiley & Sons, Ltd.",3T magnetic resonance imaging;Alzheimer's disease;apathy;apathy dimensions;brain morphometry;diffusion tensor imaging;vascular damage,"Aguera-Ortiz, L.;Hernandez-Tamames, J. A.;Martinez-Martin, P.;Cruz-Orduna, I.;Pajares, G.;Lopez-Alvarez, J.;Osorio, R. S.;Sanz, M.;Olazaran, J.",2017,Aug,,0,5695
5695,Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study,"OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD). METHODS: The setting of the study was at the Alzheimer Center Reina Sofia Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted. RESULTS: Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 +/- 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected). CONCLUSIONS: Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright (c) 2016 John Wiley & Sons, Ltd.",3T magnetic resonance imaging;Alzheimer's disease;apathy;apathy dimensions;brain morphometry;diffusion tensor imaging;vascular damage,"Aguera-Ortiz, L.;Hernandez-Tamames, J. A.;Martinez-Martin, P.;Cruz-Orduna, I.;Pajares, G.;Lopez-Alvarez, J.;Osorio, R. S.;Sanz, M.;Olazaran, J.",2016,Jul 18,10.1002/gps.4548,0,
5696,Migraine and cerebrovascular disease,"The association between migraine and stroke is complex and bidirectional. Epidemiological studies suggest that migraine may be a risk factor for stroke; magnetic resonance studies suggest that white matter abnormalities may be more frequent in migraine patients than in controls; and stroke may occur during the course of a migraine with aura (MA) attack (migrainous stroke). However, the relationship between migraine, aura and stroke is complex and mechanisms other than a direct cause/effect relationship are possible. Migraine aura may be the consequence, rather than the cause of cerebral ischaemia. Furthermore both MA and stroke may be secondary to a third underlying condition. In this review we analyse data regarding the relationship between migraine and stroke considering 3 aspects: (1) migraine as a risk factor for stroke, (2) migraine as a cause of stroke and (3) migraine and cerebral ischaemia sharing a common cause. © Springer-VerlagItalia 2007.",apolipoprotein A;blood clotting factor 5 Leiden;cyanocobalamin;elastase;ergotamine;homocysteine;nonsteroid antiinflammatory agent;Notch3 receptor;oral contraceptive agent;phospholipid antibody;prothrombin;triptan derivative;von Willebrand factor;article;brain arteriovenous malformation;brain ischemia;CADASIL;cerebrovascular accident;cerebrovascular disease;disease association;disease course;enzyme activity;human;incidence;MELAS syndrome;migraine;migraine with aura;migraine without aura;nuclear magnetic resonance imaging;pathogenesis;prevalence;risk factor;smoking;spreading cortical depression;thrombocyte aggregation,"Agostoni, E.;Rigamonti, A.",2007,,,0,
5697,White matter damage in frontotemporal lobar degeneration spectrum,"White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures.","Aged;Aphasia, Primary Progressive/ pathology;Atrophy;Brain/ pathology;Diagnosis, Differential;Diffusion Tensor Imaging/ methods;Female;Frontotemporal Lobar Degeneration/ pathology;Humans;Male;Middle Aged;Nerve Fibers, Myelinated/ pathology;Reproducibility of Results;Sensitivity and Specificity","Agosta, F.;Scola, E.;Canu, E.;Marcone, A.;Magnani, G.;Sarro, L.;Copetti, M.;Caso, F.;Cerami, C.;Comi, G.;Cappa, S. F.;Falini, A.;Filippi, M.",2012,Dec,10.1093/cercor/bhr288,0,
5698,White matter damage in Alzheimer disease and its relationship to gray matter atrophy,"PURPOSE: To explore the regional patterns of white matter (WM) tract damage in (a) patients with probable Alzheimer disease (AD) and (b) patients with amnestic mild cognitive impairment (aMCI) and at least one abnormal biomarker and to investigate whether WM damage is related to gray matter (GM) atrophy. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained from each participant. Twenty-three patients with AD, 15 patients with aMCI, and 15 healthy control subjects underwent diffusion tensor magnetic resonance imaging. WM tract damage was investigated by using tract-based spatial statistics, and GM atrophy was measured by using voxel-based morphometry. RESULTS: Compared with control subjects, patients with AD had an increase in mean diffusivity in all major WM tracts studied, including the limbic, cortico-cortical, interhemispheric, and corticospinal tracts. Conversely, fractional anisotropy decreased only in the parahippocampal tract, fornix, and small, inferior parietal regions. In addition, patients with AD showed a widespread increase in axial and radial diffusivity compared with control subjects. Patients with aMCI showed an increase in axial diffusivity only in tracts projecting to the frontal cortex and splenium of the corpus callosum. Significant and anatomically congruent correlations between WM changes and regional GM atrophy were found in patients with AD. Conversely, damage to most WM tracts in patients with aMCI did not correlate with GM atrophy. CONCLUSION: In AD, the observed patterns of WM abnormalities may reflect the advanced phase of a secondary degenerative process and an association, especially in the early phases of the disease, with primary WM tract damage over and above GM abnormalities.","Aged;Alzheimer Disease/ pathology/psychology;Atrophy/pathology;Biomarkers/analysis;Case-Control Studies;Cognition Disorders/pathology/psychology;Diffusion Magnetic Resonance Imaging/ methods;Female;Humans;Male;Nerve Fibers, Myelinated/ pathology;Neuropsychological Tests;Prospective Studies;Statistics, Nonparametric","Agosta, F.;Pievani, M.;Sala, S.;Geroldi, C.;Galluzzi, S.;Frisoni, G. B.;Filippi, M.",2011,Mar,10.1148/radiol.10101284,0,
5699,Language networks in semantic dementia,"Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.","Aged;Corpus Callosum/pathology/physiology;Female;Frontotemporal Lobar Degeneration/pathology/ physiopathology;Humans;Language;Male;Middle Aged;Nerve Fibers, Myelinated/pathology/physiology;Nerve Net/pathology/ physiology;Neuronal Plasticity/physiology;Semantics","Agosta, F.;Henry, R. G.;Migliaccio, R.;Neuhaus, J.;Miller, B. L.;Dronkers, N. F.;Brambati, S. M.;Filippi, M.;Ogar, J. M.;Wilson, S. M.;Gorno-Tempini, M. L.",2010,Jan,10.1093/brain/awp233,0,
5700,MRI signatures of the frontotemporal lobar degeneration continuum,"OBJECTIVE: To identify overlapping and unique grey (GM) and white matter (WM) signatures within the frontotemporal lobar degeneration (FTLD) continuum, and discriminate likely FTLD-TAU and FTLD-TDP patients using structural and diffusion tensor (DT) magnetic resonance imaging (MRI). METHODS: T1-weighted and DT MRI were collected from 121 subjects: 35 motor neuron disease (MND), 14 behavioral variant of frontotemporal dementia, 12 semantic and 11 nonfluent primary progressive aphasia, 21 progressive supranuclear palsy syndrome patients, and 28 healthy controls. Patterns of GM atrophy were established using voxel-based morphometry. Tract-based spatial statistics was used to perform a WM voxelwise analysis of mean diffusivity and fractional anisotropy. RESULTS: In all clinical FTLD phenotypes, the pattern of WM damage was more distributed than that of GM atrophy. All patient groups, with the exception of MND cases with a pure motor syndrome, shared a focal GM atrophy centered around the dorsolateral and medial frontal cortex and a largely overlapping pattern of WM damage involving the genu and body of the corpus callosum and ventral frontotemporal and dorsal frontoparietal WM pathways. Surrounding this common area, phenotype (symptom)-specific GM and WM regions of damage were found in each group. CONCLUSIONS: In the FTLD spectrum, WM disruption is more severe than GM damage. Frontal cortex and WM pathways represent the common target of neurodegeneration in these conditions. The topographic pattern of damage supports a ""prion-like"" protein propagation through WM connections as underlying mechanism of the stereotyped progression of FTLD.","Adult;Aged;Aged, 80 and over;Atrophy/pathology;Diffusion Tensor Imaging/methods;Female;Frontotemporal Dementia/pathology;Frontotemporal Lobar Degeneration/ pathology;Gray Matter/ pathology;Humans;Magnetic Resonance Imaging/ methods;Male;Middle Aged;Motor Neuron Disease/ pathology;Primary Progressive Nonfluent Aphasia/pathology;Supranuclear Palsy, Progressive/ pathology;White Matter/ pathology","Agosta, F.;Galantucci, S.;Magnani, G.;Marcone, A.;Martinelli, D.;Antonietta Volonte, M.;Riva, N.;Iannaccone, S.;Ferraro, P. M.;Caso, F.;Chio, A.;Comi, G.;Falini, A.;Filippi, M.",2015,Jul,10.1002/hbm.22794,0,
5701,Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: A DT MRI study and a literature review,"Nonfluent (NFV) and semantic (SV) variants of primary progressive aphasia (PPA) are associated with distinct patterns of focal cortical atrophy and underlying pathology. Previous diffusion tensor (DT) MRI studies showed a more ventral white matter (WM) involvement in SV patients and a more widespread frontal involvement in NFV. Aim of this manuscript is twofold. First, we wished to provide a brief state-of-the-art review on WM damage in PPA. Second, we used DT MRI to assess the topography of WM microstructural damage along dorsal and ventral language pathways and corpus callosum in patients with NFV and SV. Our findings show that the two PPA variants share an overlapping pattern of dorsal and ventral pathway abnormalities. In addition to these common abnormalities, variant-specific WM changes were also found, with NFV patients having a more severe damage to the dorsal (fronto-parietal) WM connections within the left superior longitudinal fasciculus/arcuate and SV patients showing a greater left ventral tract involvement (inferior longitudinal and uncinate fasciculi). These findings offer evidence that both dorsal and ventral language networks may contribute to the relatively selective deficits in NFV and SV patients. © 2013 Elsevier Inc.",TAR DNA binding protein;tau protein;aged;arcuate nucleus;article;cell activation;clinical article;cognition;controlled study;corpus callosum;diffusion tensor imaging;disease association;female;fluency disorder;frontotemporal dementia;human;inferior longitudinal fasciculus;left hemisphere;male;microglia;nerve fiber degeneration;nerve tract;neuroanatomy;neuroimaging;nonfluent primary progressive aphasia;primary progressive aphasia;semantic primary progressive aphasia;semantics;superior longitudinal fasciculus;tauopathy;uncinate fasciculus;voxel based morphometry;white matter lesion,"Agosta, F.;Galantucci, S.;Canu, E.;Cappa, S. F.;Magnani, G.;Franceschi, M.;Falini, A.;Comi, G.;Filippi, M.",2013,,,0,
5702,Structural and functional brain signatures of C9orf72 in motor neuron disease,"This study investigated structural and functional magnetic resonance imaging abnormalities in hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) motor neuron disease (MND) relative to disease severity-matched sporadic MND cases. We enrolled 19 C9orf72 and 67 disease severity-matched sporadic MND patients, and 22 controls. Sporadic cases were grouped in patients with: no cognitive/behavioral deficits (sporadic-motor); same patterns of cognitive/behavioral impairment as C9orf72 cases (sporadic-cognitive); shorter disease duration versus other sporadic groups (sporadic-early). C9orf72 patients showed cerebellar and thalamic atrophy versus all sporadic cases. All MND patients showed motor, frontal, and temporoparietal cortical thinning and motor and extramotor white matter damage versus controls, independent of genotype and presence of cognitive impairment. Compared with sporadic-early, C9orf72 patients revealed an occipital cortical thinning. C9orf72 patients had enhanced visual network functional connectivity versus sporadic-motor and sporadic-early cases. Structural cerebellar and thalamic damage and posterior cortical alterations are the brain magnetic resonance imaging signatures of C9orf72 MND. Frontotemporal cortical and widespread white matter involvement are likely to be an effect of the disease evolution rather than a C9orf72 marker.",adult;aged;article;behavior disorder;brain atrophy;brain size;C9orf72 gene;cerebellum;cognitive defect;controlled study;cortical thickness (brain);cuneus;dementia;diffusion tensor imaging;disease duration;disease severity;female;functional connectivity;functional magnetic resonance imaging;functional neuroimaging;fusiform gyrus;human;lingual gyrus;major clinical study;male;middle occipital gyrus;motor cortex;motor dysfunction;motor neuron disease;nuclear magnetic resonance scanner;occipital cortex;occipital gyrus;parietal cortex;prefrontal cortex;priority journal;superior occipital gyrus;temporal cortex;thalamus;white matter lesion;Intera,"Agosta, F.;Ferraro, P. M.;Riva, N.;Spinelli, E. G.;Domi, T.;Carrera, P.;Copetti, M.;Falzone, Y.;Ferrari, M.;Lunetta, C.;Comi, G.;Falini, A.;Quattrini, A.;Filippi, M.",2017,,10.1016/j.neurobiolaging.2017.05.024,0,
5703,Differentiation between Subtypes of Primary Progressive Aphasia by Using Cortical Thickness and Diffusion-Tensor MR Imaging Measures,"PURPOSE: To test a multimodal magnetic resonance (MR) imaging-based approach composed of cortical thickness and white matter (WM) damage metrics to discriminate between variants of primary progressive aphasia (PPA) that are nonfluent and/or agrammatic (NFVPPA) and semantic (SVPPA). MATERIALS AND METHODS: This study was approved by the local ethics committees on human studies, and written informed consent from all patients was obtained before their enrollment. T1-weighted and diffusion-tensor (DT) MR images were obtained from 13 NFVPPA patients, 13 SVPPA patients, and 23 healthy control participants. Cortical thickness and DT MR imaging indices from the long-associative and interhemispheric WM tracts were obtained. A random forest (RF) analysis was used to identify the image features associated with each clinical syndrome. Individual patient classification was performed by using receiver operator characteristic curve analysis with cortical thickness, DT MR imaging, and a combination of the two modalities. RESULTS RF analysis showed that the best markers to differentiate the two PPA variants at an individual patient level among cortical thickness and DT MR imaging metrics were diffusivity abnormalities of the left inferior longitudinal and uncinate fasciculi and cortical thickness measures of the left temporal pole and inferior frontal gyrus. A combination of cortical thickness and DT MR imaging measures (the so-called gray-matter-and-WM model) was able to distinguish patients with NFVPPA and SVPPA with the following classification pattern: area under the curve, 0.91; accuracy, 0.89; sensitivity, 0.92; specificity, 0.85. Leave-one-out analysis demonstrated that the gray matter and WM model is more robust than the single MR modality models to distinguish PPA variants (accuracy was 0.86, 0.73, and 0.68 for the gray matter and WM model, the gray matter-only model, and the WM-only model, respectively). CONCLUSION: A combination of structural and DT MR imaging metrics may provide a quantitative procedure to distinguish NFVPPA and SVPPA patients at an individual patient level. The discrimination accuracies obtained suggest that the gray matter and WM model is potentially relevant for the differential diagnosis of the PPA variants in clinical practice.","Aged;Aphasia, Primary Progressive/ classification/ pathology;Cerebral Cortex/ pathology;Diagnosis, Differential;Diffusion Tensor Imaging;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged","Agosta, F.;Ferraro, P. M.;Canu, E.;Copetti, M.;Galantucci, S.;Magnani, G.;Marcone, A.;Valsasina, P.;Sodero, A.;Comi, G.;Falini, A.;Filippi, M.",2015,Jul,10.1148/radiol.15141869,0,
5704,Myeloid microvesicles in cerebrospinal fluid are associated with myelin damage and neuronal loss in mild cognitive impairment and Alzheimer disease,"OBJECTIVES: We have described cerebrospinal fluid (CSF) myeloid microvesicles (MVs) as a marker of microglia activation during neuroinflammation in Alzheimer disease (AD), and characterized their ability to produce toxic amyloid beta1-42 (Abeta1-42 ) oligomers from aggregated or soluble substrate. The aim of this study is to investigate the association of CSF myeloid MVs with neuroimaging, clinical, and paraclinical data in AD and mild cognitive impairment (MCI). METHODS: We collected CSF from 106 AD patients, 51 MCI patients, and 29 neurologically healthy controls. We examined CSF myeloid MV content and AD markers. A subgroup of 34 AD and 21 MCI patients underwent structural and diffusion tensor MRI. RESULTS: Higher levels of myeloid MVs were found in the CSF of AD patients and MCI patients converting within 3 years relative to controls, but also, at a lower level, in MCI patients not converting to AD. CSF myeloid MVs were associated with Tau but not with Abeta1-42 CSF levels. CSF MVs levels correlated with white matter (WM) tract damage in MCI, and with hippocampal atrophy in AD. INTERPRETATION: Microglial MVs are neurotoxic and myelinotoxic in the presence of Abeta1-42 . CSF myeloid MVs, mirroring microglia activation and MV release, are associated with WM damage in MCI and hippocampal atrophy in AD. This suggests that hippocampal microglia activation, in the presence of Abeta1-42 in excess, produces neurotoxic and oligodendrotoxic oligomers that, through WM tract damage, spread disease to neighboring and connected areas, causing local microglia activation and propagation of disease through the same sequence of events. Ann Neurol 2014;76:813-825.","Aged;Aged, 80 and over;Alzheimer Disease/*cerebrospinal fluid/diagnosis;Biomarkers/cerebrospinal fluid;Cell Count/methods;Female;Humans;Male;Middle Aged;Mild Cognitive Impairment/*cerebrospinal fluid/diagnosis;Myelin Sheath/*metabolism/pathology;Myeloid Cells/*metabolism/pathology;Neurons/*metabolism/pathology","Agosta, F.;Dalla Libera, D.;Spinelli, E. G.;Finardi, A.;Canu, E.;Bergami, A.;Bocchio Chiavetto, L.;Baronio, M.;Comi, G.;Martino, G.;Matteoli, M.;Magnani, G.;Verderio, C.;Furlan, R.",2014,Dec,10.1002/ana.24235,0,
5705,Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage,"This study assesses the patterns of gray matter (GM) and white matter (WM) damage in patients with Parkinson's disease and mild cognitive impairment (PD-MCI) compared with healthy controls and cognitively unimpaired PD patients (PD-Cu). Three-dimensional T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were obtained from 43 PD patients and 33 healthy controls. Cognition was assessed using a neuropsychological battery. Tract-based spatial statistics was applied to compare DT MRI indices between groups on a voxel-by-voxel basis. Voxel-based morphometry was performed to assess GM atrophy. Thirty PD patients were classified as MCI. Compared with healthy controls, PD-Cu and PD-MCI patients did not have GM atrophy. No region of WM damage was found in PD-Cu patients when compared with healthy controls. Relative to healthy controls and PD-Cu patients, PD-MCI patients showed a distributed pattern of WM abnormalities in the anterior and superior corona radiata, genu, and body of the corpus callosum, and anterior inferior fronto-occipital, uncinate, and superior longitudinal fasciculi, bilaterally. Subtle cognitive decline in PD is associated with abnormalities of frontal and interhemispheric WM connections, and not with GM atrophy. DT MRI might contribute to the identification of structural changes in PD-MCI patients prior to the development of dementia.","Aged;Aged, 80 and over;Brain Mapping;Female;Humans;Image Processing, Computer-Assisted;Magnetic Resonance Imaging;Male;Middle Aged;Mild Cognitive Impairment/ etiology/ pathology;Neuropsychological Tests;Parkinson Disease/complications/ pathology;Severity of Illness Index;White Matter/ pathology","Agosta, F.;Canu, E.;Stefanova, E.;Sarro, L.;Tomic, A.;Spica, V.;Comi, G.;Kostic, V. S.;Filippi, M.",2014,May,10.1002/hbm.22302,0,
5706,Nuclear magnetic resonance imaging in the aging brain,"43 patients aged over 55 years with different clinical diagnoses but with the common aspect of impairment of the cognitive functions underwent a 0.5 Tesla magnetic resonance imaging (MRI) investigation in order to obtain further information about the pathological causes underlying the clinical syndromes. The occurrence of white matter signal alterations (periventricular lucency) and of multifocal ischemic areas represented the most frequent and atypical finding. Independently of the clinical focal symptomatology, these data might well represent a marker of a diffuse tissue sufferance due to a chronic mild cerebral hypoperfusion. The incidence of similar findings in 'normal' elderly subjects must be assessed before giving them a definite relevance in the evaluation of the pathological aging.",,"Agnoli, A.;Feliciani, M.",1987,1987,,0,
5707,The association of magnetic resonance imaging measures with cognitive function in a biracial population sample,"BACKGROUND: White matter hyperintensity volume (WMHV), cerebral infarcts, and total brain volume (TBV) are associated with cognitive function, but few studies have examined these associations in the general population or whether they differ by race. OBJECTIVE: To examine the association of WMHV, cerebral infarcts, and TBV with global cognition and cognition in 5 separate domains in a biracial population sample. SETTING: A biracial community population of Chicago, Illinois. DESIGN: Cross-sectional population study. PARTICIPANTS: The study population comprised 575 participants from the Chicago Health and Aging Project (CHAP). MAIN OUTCOME MEASURES: Volumetric magnetic resonance imaging (MRI) measures of WMHV, TBV, and cerebral infarcts and detailed neuropsychological testing assessments of global cognition and 5 cognitive domains. RESULTS: Overall and among those without dementia, cognition was inversely associated with WMHV and number of infarcts but was positively associated with TBV. When all 3 measures were simultaneously added to the model, the association of global cognition with WMHV and TBV remained significant and unchanged but was no longer significant with infarcts. Among subjects without dementia, all 3 MRI measures were associated with performance in multiple cognitive domains, specifically perceptual speed. However, among subjects with dementia, only TBV was associated with cognition and performance in multiple cognitive systems. Race did not significantly modify any of these associations. CONCLUSIONS: In this biracial general population sample, the associations of MRI measures with cognition differed according to clinical status of subjects (stronger among subjects without dementia) and were not modified by race. These associations did not affect all cognitive domains equally but were more consistent with impairments in perceptual speed.","African Continental Ancestry Group;Aged;Aged, 80 and over;Brain/ pathology/physiopathology;Brain Infarction/epidemiology/ ethnology/ pathology;Brain Mapping;Cerebrovascular Disorders/epidemiology/ethnology/pathology;Cognition/physiology;Cognition Disorders/epidemiology/ ethnology/ pathology;Cohort Studies;Comorbidity;Continental Population Groups;Cross-Sectional Studies;Disease Progression;European Continental Ancestry Group;Female;Humans;Magnetic Resonance Imaging;Male;Nerve Fibers, Myelinated/pathology;Neuropsychological Tests;Psychometrics;Risk Factors","Aggarwal, N. T.;Wilson, R. S.;Bienias, J. L.;De Jager, P. L.;Bennett, D. A.;Evans, D. A.;DeCarli, C.",2010,Apr,10.1001/archneurol.2010.42,0,
5708,Characteristics of MR infarcts associated with dementia and cognitive function in the elderly,"BACKGROUND: Little information exists on the simultaneous effects of magnetic resonance (MR) infarct characteristics, that may increase the likelihood of dementia or lower cognitive function in community populations. METHODS: Participants were 580 community-dwelling individuals from the Chicago Health and Aging Project (CHAP) who underwent detailed clinical evaluation and MR imaging. The association of MR infarct characteristics (region, number, side, and size) with dementia, global cognition and cognition in five separate cognitive domains was examined using logistic and linear regression analyses controlling for age, sex, race, education and time elapsed between clinical evaluation and MRI. RESULTS: A total of 156 persons had MR infarcts: 108 with 1 infarct and 48 with multiple. Poorer cognitive function and, in particular, slower perceptual speed, were associated with infarcts characterized as cortical, multiple, bilateral or large (all p < 0.05). Multiple infarcts in multiple regions were associated with poor performance in all cognitive domains except visuospatial ability (p < 0.05). Race did not modify any of these associations. CONCLUSIONS: In this community sample, cortical and multiple infarcts in multiple regions were associated with dementia; cortical, multiple, large and bilateral infarcts were associated with lower cognition, particularly lower memory function and perceptual speed. These effects were not modified by race.","Age Distribution;Aged;Aged, 80 and over;Causality;Cerebral Infarction/ diagnosis/ epidemiology;Chicago/epidemiology;Cognition Disorders/ epidemiology;Cohort Studies;Comorbidity;Dementia/ epidemiology;Female;Humans;Logistic Models;Longitudinal Studies;Magnetic Resonance Imaging;Male;Odds Ratio;Sex Distribution","Aggarwal, N. T.;Schneider, J. A.;Wilson, R. S.;Beck, T. L.;Evans, D. A.;Carli, C. D.",2012,,10.1159/000334438,0,
5709,Perceived stress is associated with subclinical cerebrovascular disease in older adults,"Objective: To examine the association of perceived stress with magnetic resonance imaging (MRI) markers of subclinical cerebrovascular disease in an elderly cohort. Methods: Using a cross-sectional study of a community-based cohort in Chicago, 571 adults (57% women; 58.1% African American; 41.9% non-Hispanic white; mean [SD] age: 79.8 [5.9] years) from the Chicago Health and Aging Project, an epidemiologic study of aging, completed questionnaires on perceived stress, medical history, and demographics as part of an in-home assessment and 5 years later underwent a clinical neurologic examination and MRI of the brain. Outcome measures were volumetric MRI assessments of white matter hyperintensity volume (WMHV), total brain volume (TBV), and cerebral infarction. Results: Stress was measured with six items from the Perceived Stress Scale (PSS); item responses, ranging from never (0) to often (3), were summed to create an overall stress score (mean [SD]: 4.9 [3.3]; range: 0-18). Most participants had some evidence of vascular disease on MRI, with 153 participants (26.8%) having infarctions. In separate linear and logistic regression models adjusted for age, sex, education, race, and time between stress assessment and MRI, each one-point increase in PSS score was associated with significantly lower TBV (coefficient = -0.111, SE = 0.049, t[563] = -2.28, p = 0.023) and 7% greater odds of infarction (odds ratio: 1.07; 95% confidence interval: 1.01, 1.13; Wald ×(2)[1] = 4.90; p = 0.027). PSS scores were unrelated to WMHV. Results wereunchanged with further adjustment for smoking, body mass index, physical activity, history of heart disease, stroke, diabetes, hypertension, depressive symptoms, and dementia. Conclusions: Greater perceived stress was significantly and independently associated with cerebral infarction and lower brain volume assessed 5 years later in this elderly cohort. © 2014 American Association for Geriatric Psychiatry.",,"Aggarwal, N. T.;Clark, C. J.;Beck, T. L.;De Leon, C. F. M.;DeCarli, C.;Evans, D. A.;Rose, S. A. E.",2014,January,,0,
5710,White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease,"INTRODUCTION: Little is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype. METHODS: This study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47-76 years). RESULTS: Both APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity. CONCLUSION: APOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics-both expected and unexpected-may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.","Age Factors;Aged;Alzheimer Disease/ genetics/ pathology;Apolipoprotein E4/ genetics;Diffusion Tensor Imaging;Family Health;Female;Genotype;Humans;Image Processing, Computer-Assisted;Male;Middle Aged;Multivariate Analysis;Parents;White Matter/ pathology","Adluru, N.;Destiche, D. J.;Lu, S. Y.;Doran, S. T.;Birdsill, A. C.;Melah, K. E.;Okonkwo, O. C.;Alexander, A. L.;Dowling, N. M.;Johnson, S. C.;Sager, M. A.;Bendlin, B. B.",2014,,10.1016/j.nicl.2014.04.008,0,
5711,"17q25 locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status","Background and Purpose-Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods-We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These singlenucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results-Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions-This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction. © 2013 American Heart Association, Inc.",adult;aged;article;brain ischemia;chromosome 17q;chromosome 17q 25;controlled study;disease association;female;gene locus;genetic association;genetic risk;genetic variability;human;lacunar stroke;major clinical study;male;priority journal;scoring system;single nucleotide polymorphism;white matter,"Adib-Samii, P.;Rost, N.;Traylor, M.;Devan, W.;Biffi, A.;Lanfranconi, S.;Fitzpatrick, K.;Bevan, S.;Kanakis, A.;Valant, V.;Gschwendtner, A.;Malik, R.;Richie, A.;Gamble, D.;Segal, H.;Parati, E. A.;Ciusani, E.;Holliday, E. G.;Maguire, J.;Wardlaw, J.;Worrall, B.;Bis, J.;Wiggins, K. L.;Longstreth, W.;Kittner, S. J.;Cheng, Y. C.;Mosley, T.;Falcone, G. J.;Furie, K. L.;Leiva-Salinas, C.;Lau, B. C.;Khan, M. S.;Sharma, P.;Fornage, M.;Mitchell, B. D.;Psaty, B. M.;Sudlow, C.;Levi, C.;Boncoraglio, G. B.;Rothwell, P. M.;Meschia, J.;Dichgans, M.;Rosand, J.;Markus, H. S.",2013,,,0,
5712,Genetic architecture of white matter hyperintensities differs in hypertensive and nonhypertensive ischemic stroke,"BACKGROUND AND PURPOSE - : Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. METHODS - : WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups stratified by risk factors found to be significant in multivariate analyses. RESULTS - : A significant proportion of the variance of WMHV was attributable to common SNPs after adjustment for significant risk factors (HSNP=0.23; P=0.0026). HSNP estimates were higher among hypertensive individuals (HSNP=0.45; P=7.99×10); this increase was greater than expected by chance (P=0.012). In contrast, estimates were lower, and nonsignificant, in nonhypertensive individuals (HSNP=0.13; P=0.13). CONCLUSIONS - : A quarter of variance is attributable to common SNPs, but this estimate was greater in hypertensive individuals. These findings suggest that the genetic architecture of WMH in ischemic stroke differs between hypertensives and nonhypertensives. Future WMHV GWAS studies may gain power by accounting for this interaction.",aged;article;brain ischemia;cardiovascular risk;cerebrovascular accident;female;genetic association;genetic correlation;genetic trait;genetic variability;genotype;hemisphere;heritability;human;hypertension;major clinical study;male;neuroimaging;neurologic disease;nuclear magnetic resonance imaging;pathophysiology;priority journal;risk factor;single nucleotide polymorphism;white matter;white matter hyperintensity;white matter lesion,"Adib-Samii, P.;Devan, W.;Traylor, M.;Lanfranconi, S.;Zhang, C. R.;Cloonan, L.;Falcone, G. J.;Radmanesh, F.;Fitzpatrick, K.;Kanakis, A.;Rothwell, P. M.;Sudlow, C.;Boncoraglio, G. B.;Meschia, J. F.;Levi, C.;Dichgans, M.;Bevan, S.;Rosand, J.;Rost, N. S.;Markus, H. S.",2015,,,0,
5713,3D scattering transforms for disease classification in neuroimaging,"Classifying neurodegenerative brain diseases in MRI aims at correctly assigning discrete labels to MRI scans. Such labels usually refer to a diagnostic decision a learner infers based on what it has learned from a training sample of MRI scans. Classification from MRI voxels separately typically does not provide independent evidence towards or against a class; the information relevant for classification is only present in the form of complicated multivariate patterns (or ""features""). Deep learning solves this problem by learning a sequence of non-linear transformations that result in feature representations that are better suited to classification. Such learned features have been shown to drastically outperform hand-engineered features in computer vision and audio analysis domains. However, applying the deep learning approach to the task of MRI classification is extremely challenging, because it requires a very large amount of data which is currently not available. We propose to instead use a three dimensional scattering transform, which resembles a deep convolutional neural network but has no learnable parameters. Furthermore, the scattering transform linearizes diffeomorphisms (due to e.g. residual anatomical variability in MRI scans), making the different disease states more easily separable using a linear classifier. In experiments on brain morphometry in Alzheimer's disease, and on white matter microstructural damage in HIV, scattering representations are shown to be highly effective for the task of disease classification. For instance, in semi-supervised learning of progressive versus stable MCI, we reach an accuracy of 82.7%. We also present a visualization method to highlight areas that provide evidence for or against a certain class, both on an individual and group level.",Feature extraction;MRI classification;Scattering representation,"Adel, T.;Cohen, T.;Caan, M.;Welling, M.;group, A. GEhIV study;the Alzheimer's Disease Neuroimaging, Initiative",2017,,,0,
5714,A priori collaboration in population imaging: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium,"Introduction: Virchow-Robin spaces (VRS), or perivascular spaces, are compartments of interstitial fluid enclosing cerebral blood vessels and are potential imaging markers of various underlying brain pathologies. Despite a growing interest in the study of enlarged VRS, the heterogeneity in rating and quantification methods combined with small sample sizes have so far hampered advancement in the field. Methods: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement (UNIVRSE) consortium was established with primary aims to harmonize rating and analysis (www.uconsortium.org). The UNIVRSE consortium brings together 13 (sub)cohorts from five countries, totaling 16,000 subjects and over 25,000 scans. Eight different magnetic resonance imaging protocols were used in the consortium. Results: VRS rating was harmonized using a validated protocol that was developed by the two founding members, with high reliability independent of scanner type, rater experience, or concomitant brain pathology. Initial analyses revealed risk factors for enlarged VRS including increased age, sex, high blood pressure, brain infarcts, and white matter lesions, but this varied by brain region. Discussion: Early collaborative efforts between cohort studies with respect to data harmonization and joint analyses can advance the field of population (neuro)imaging. The UNIVRSE consortium will focus efforts on other potential correlates of enlarged VRS, including genetics, cognition, stroke, and dementia.",,"Adams, H. H. H.;Hilal, S.;Schwingenschuh, P.;Wittfeld, K.;van der Lee, S. J.;DeCarli, C.;Vernooij, M. W.;Katschnig-Winter, P.;Habes, M.;Chen, C.;Seshadri, S.;van Duijn, C. M.;Ikram, M. K.;Grabe, H. J.;Schmidt, R.;Ikram, M. A.",2015,1,,0,
5715,An in vivo diagnosis of Creutzfeldt-Jakob disease. Case report,"A rapidly progressing dementia, followed by focal neurological signs and evidence of periodic sharp waves complexes in the EEG may lead to the clinical suspicion of Creutzfeldt-Jakob disease (CJD). Nevertheless the cases of CJD are diagnosed seldom. Patient, a 66-year-old man was admitted to Department of Neurology with progressive disturbances of communication. There was no family history of similar diseases. In the neurological examination aphasia, behavioural abnormalities and grow of muscles tension was found. There were also periodic abnormalities in EEG. The rapidly progressive worsening of consciousness persuaded us to recognizing CJD. We diagnosed him as having CJD as we detected the 14-3-3 neuronal protein in cerebrospinal fluid. Cranial MRI showed mild cerebral atrophy with periventricular white matter hyperintensity in T2-weighted scans. During the observation the contact with patient rapidly worsened and he died after two weeks hospitalisation. The CJD was proven by the typical EEG, neuronal protein in CSF and by autopsy too. This is the one of few cases diagnosed alive. © Aktualn Neurol 2006.",aged;aphasia;article;behavior disorder;brain atrophy;case report;cerebrospinal fluid;Creutzfeldt Jakob disease;EEG abnormality;hospital admission;human;male;muscle tone;neurologic examination;nuclear magnetic resonance imaging,"Adamkiewicz, B.;Fornalska, Z.;Skłodowski, P.;Liberski, P. P.;Klimek, A.",2006,,,0,
5716,Autosomal dominant cerebral arteriopathy: Neuropsychiatric syndrome in a family,"Though familial vascular leukoencephalopathy was described two decades ago, recent studies focus on a disorder termed Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a dominantly inherited disorder causing recurrent strokes and eventual dementia. The phenotypic boundaries of CADASIL remain indistinct and novel clinical features continue to arise in the literature. However, the associated histopathology is fairly consistent, typically demonstrating granular thickening of cerebral arterioles. The authors evaluated a 38-year-old man who suffered from progressive change in personality and intellect. His father, paternal aunt, and older sister had succumbed to a similar disorder. The authors examined relatives from three generations, including another sister with transient focal symptoms followed by persisting psychiatric disorder, and reviewed the radiographic studies from the propositus and his siblings. All the siblings showed diffuse white matter signal change on magnetic resonance imaging. Brain biopsy from the propositus revealed normal cortex and white matter but granular sclerosis of leptomeningeal arterioles. While the family's illness likely represents another instance of CADASIL, their presentation is unique because neuropsychiatric disorders predominate over focal ischemic symptoms.",,"Adair, J. C.;Hart, B. L.;Kornfeld, M.;Graham, G. D.;Swanda, R. M.;Ptacek, L. J.;Davis, L. E.",1998,January,,0,
5717,Autopsy case of spinocerebellar ataxia type 31 with severe dementia at the terminal stage,"Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant cerebellar ataxia commonly observed in Japan. However, few neuropathological examinations have been conducted. Here we report the case of a 76-year-old Japanese male SCA31 patient. He noticed dysarthria and difficulty walking at 65 years old. His symptoms subsequently deteriorated, although he could still walk with assistance at 70 years. At 73 years, when he could no longer walk, he was admitted to our hospital. He showed severe limb and truncal ataxia. His father and older brother had shown the same symptoms. Brain magnetic resonance imaging showed cerebellar atrophy of the anterior lobe and white matter hyperintensities. He was diagnosed with SCA31 by genetic analysis. Gradually, his cognitive functions and ability to communicate declined. He died of respiratory failure at the age of 76. Neuropathological examination revealed severe Purkinje cell loss that was accentuated in the anterior lobe of the cerebellum. Furthermore, the remaining Purkinje cells showed abnormal processes (that is, halo-like amorphous materials), as has been reported previously. Severe deposition of hyperphosphorylated tau-positive neurites, many senile plaques and amyloid angiopathy were observed in the neocortex. Our findings suggest that in SCA31, accelerated tau and amyloid pathology in the neocortex might induce dementia at the terminal stage.",,"Adachi, T.;Kitayama, M.;Nakano, T.;Adachi, Y.;Kato, S.;Nakashima, K.",2015,1,,0,
5718,Intravascular lymphomatosis: A case report,"We report a case of a 64-year-old man with intravascular lymphomatosis. He had dementia and generalized seizure. Computed tomogram scan and magnetic resonance imaging showed multiple infarctions in the right frontal lobe, right cerebellar hemisphere and left occipital lobe. A month after admission he had a daily high fever and frequent convulsions. The level of serum LDH was progressively getting higher and the level of β2-microglobulin in both serum and CSF was high. One and a half months after admission we performed an open biopsy for making a definite diagnosis by pathological examination. Histological diagnosis was intravascular lymphomatosis (angiotrophic lymphoma) of large B cell type. He was treated with regimens of combined chemotherapy with M-CHOP (methotrexate, cyclophosphamide, adriamycin, vincristine, prednisolone). After chemotherapy his consciousness was gradually improving better and the level of serum LDH and β2-microglobulin was reduced to a low level. Three months after admission he died of respiratory failure. After a review of the literature and experience with this case, it is obious that early diagnosis of this disease is difficult. However, we think that multiple cerebral infarctions on neuroradiological examinations and high levels of serum LDH (especially LDH(2) and LDH(3)) and β2-microglobulin in CSF and serum should lead to a presumptive diagnosis of this disease, and biopsy should be used to make a difinite diagnosis.",,"Adachi, H.;Tsuboi, M.;Hayashi, K.",2001,2001,,0,
5719,Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease,"Recent imaging evidence in Alzheimer's disease suggests that neural involvement in early-stage disease is more complex than is encapsulated in the commonly held position of predominant mesial temporal lobe degeneration-there is also early posterior cingulate cortex and diencephalic damage. These findings suggest that early clinical Alzheimer's disease is underpinned by damage to an inter-connected network. If correct, this hypothesis would predict degeneration of the white matter pathways that connect this network. This prediction can be tested in vivo by diffusion magnetic resonance imaging. Most diffusion tensor imaging studies of white matter in neurodegenerative disorders such as Alzheimer's disease have concentrated on fractional anisotropy reductions and increased 'apparent' diffusivity; however, there is a lack of empirical biological evidence to assume that fractional anisotropy changes will necessarily capture the full extent of white matter changes in Alzheimer's disease. In this study, therefore, we undertook a comprehensive investigation of diffusion behaviour in Alzheimer's disease by analysing each of the component eigenvalues of the diffusion tensor in isolation to test the hypothesis that early Alzheimer's disease is associated with degeneration of a specific neural network. Using tract-based spatial statistics, we performed voxel-wise analyses of fractional anisotropy, axial, radial and mean diffusivities in 25 Alzheimer's disease patients compared with 13 elderly controls. We found that increased absolute (axial, radial and mean) diffusivities in Alzheimer's disease were concordant in a distribution consistent with the network hypothesis, highly statistically significant and far more sensitive than fractional anisotropy reductions. The former three measures identified confluent white matter abnormalities in parahippocampal gyrus and posterior cingulum, extending laterally into adjacent temporo-parietal regions as well as splenium and fornix. The caudal occipital lobe, temporal pole, genu and prefrontal white matter were relatively preserved. This distribution is highly consistent with expected predictions of tract degeneration from grey matter lesions identified by fluorodeoxyglucose positron emission tomography and structural magnetic resonance imaging. Concordant with results from these other imaging modalities, this pattern predominantly involves degeneration of the tracts connecting the circuit of Papez. These findings also highlight that early neuropathological processes are associated with changes of the diffusion ellipsoid that are predominantly proportional along all semi-principal axes.",,"Acosta-Cabronero, J.;Williams, G. B.;Pengas, G.;Nestor, P. J.",2010,February,,0,
5720,In vivo quantitative susceptibility mapping (QSM) in Alzheimer's disease,"BACKGROUND: This study explores the magnetostatic properties of the Alzheimer's disease brain using a recently proposed, magnetic resonance imaging, postprocessed contrast mechanism. Quantitative susceptibility mapping (QSM) has the potential to monitor in vivo iron levels by reconstructing magnetic susceptibility sources from field perturbations. However, with phase data acquired at a single head orientation, the technique relies on several theoretical approximations and requires fast-evolving regularisation strategies. METHODS: In this context, the present study describes a complete methodological framework for magnetic susceptibility measurements with a review of its theoretical foundations. FINDINGS AND SIGNIFICANCE: The regional and whole-brain cross-sectional comparisons between Alzheimer's disease subjects and matched controls indicate that there may be significant magnetic susceptibility differences for deep brain nuclei--particularly the putamen--as well as for posterior grey and white matter regions. The methodology and findings described suggest that the QSM method is ready for larger-scale clinical studies.","Adult;Aged;Alzheimer Disease/ diagnosis;Brain/ pathology;Brain Mapping;Case-Control Studies;Female;Humans;Image Interpretation, Computer-Assisted/methods;Image Processing, Computer-Assisted/methods;Magnetic Resonance Imaging/methods;Male;Reproducibility of Results","Acosta-Cabronero, J.;Williams, G. B.;Cardenas-Blanco, A.;Arnold, R. J.;Lupson, V.;Nestor, P. J.",2013,,10.1371/journal.pone.0081093,0,
5721,"Atrophy, hypometabolism and white matter abnormalities in semantic dementia tell a coherent story","Semantic dementia, in which there is progressive deterioration of semantic knowledge, is associated with focal, typically asymmetric, temporal lobe degeneration. The ventrorostral temporal lobe is most severely affected and there is concordance between atrophy and reduced metabolic activity. In this study, we confirmed the veracity of this claim using (1)F-fluorodeoxyglucose positron emission tomography and anatomical magnetic resonance images. The principal aim, however, was to understand the impact on neuronal projections from the ventrorostral temporal cortex lesion by studying the full extent of white matter changes, with no a priori assumptions about the nature or spatial location of the tracts involved. Using an unbiased voxel-wise approach known as tract-based spatial statistics, we compared results of whole-brain diffusion tensor imaging--absolute metrics of axial, radial and mean diffusion as well as fractional anisotropy--from 10 patients with mild/moderate semantic dementia and 21 matched controls. Distributions of increased absolute diffusivity and reduced fractional anisotropy for patients with semantic dementia were spatially concordant with each other. Abnormalities in all metrics were highly statistically significant in ventrorostral temporal white matter, more extreme on the left side, thus closely matching results from structural and functional imaging of grey matter. The most sensitive marker of change was radial diffusion. Local white matter tract abnormalities extended rostrally towards the frontal lobe and dorsocaudally towards the superior temporal and supramarginal gyri. To examine more remote changes, we performed a skeletonized probabilistic tractography analysis--'seeding' the rostral temporal voxels identified as abnormal in the patient group--in a healthy control group. Three major neural pathways were found to emanate from this 'seed region': uncinate, arcuate and inferior longitudinal fasciculi. At a less conservative threshold, tensor abnormalities in the semantic dementia group mapped onto the tractographies for the uncinate and arcuate bundles well beyond the rostral temporal lobe; this was not the case for the inferior longitudinal bundle, where abnormalities in semantic dementia did not extend caudal to the atrophic/hypometabolic zone. The results offer direct evidence for how the ventrorostral temporal lesion, proposed to be responsible for deteriorating semantic knowledge in semantic dementia and separate from 'classic' language areas, is associated with degeneration of efferent white matter projections to such language areas.",,"Acosta-Cabronero, J.;Patterson, K.;Fryer, T. D.;Hodges, J. R.;Pengas, G.;Williams, G. B.;Nestor, P. J.",2011,Jul,,0,
5722,Diffusion tensor imaging in Alzheimer's disease: Insights into the limbic-diencephalic network and methodological considerations,"Glucose hypometabolism and grey matter atrophy are well known consequences of Alzheimer's disease (AD). Studies using these measures have shown that the earliest clinical stages, in which memory impairment is a relatively isolated feature, are associated with degeneration in an apparently remote group of areas-mesial temporal lobe (MTL), diencephalic structures such as anterior thalamus and mammillary bodies, and posterior cingulate. These sites are thought to be strongly anatomically inter-connected via a limbic-diencephalic network. Diffusion tensor imaging or DTI - an imaging technique capable of probing white matter tissue microstructure - has recently confirmed degeneration of the white matter connections of the limbic-diencephalic network in AD by way of an unbiased analysis strategy known as tract-based spatial statistics (TBSS). The present review contextualizes the relevance of these findings, in which the fornix is likely to play a fundamental role in linking MTL and diencephalon. An interesting by-product of this work has been in showing that alterations in diffusion behavior are complex in AD - while early studies tended to focus on fractional anisotropy, recent work has highlighted that this measure is not the most sensitive to early changes. Finally, this review will discuss in detail several technical aspects of DTI both in terms of image acquisition and TBSS analysis as both of these factors have important implications to ensure reliable observations are made that inform understanding of neurodegenerative diseases.",,"Acosta-Cabronero, J.;Nestor, P. J.",2014,,,0,
5723,Diffusion tensor metrics as biomarkers in Alzheimer's disease,"BACKGROUND: Although diffusion tensor imaging has been a major research focus for Alzheimer's disease in recent years, it remains unclear whether it has sufficient stability to have biomarker potential. To date, frequently inconsistent results have been reported, though lack of standardisation in acquisition and analysis make such discrepancies difficult to interpret. There is also, at present, little knowledge of how the biometric properties of diffusion tensor imaging might evolve in the course of Alzheimer's disease. METHODS: The biomarker question was addressed in this study by adopting a standardised protocol both for the whole brain (tract-based spatial statistics), and for a region of interest: the midline corpus callosum. In order to study the evolution of tensor changes, cross-sectional data from very mild (N = 21) and mild (N = 22) Alzheimer's disease patients were examined as well as a longitudinal cohort (N = 16) that had been rescanned at 12 months. FINDINGS AND SIGNIFICANCE: The results revealed that increased axial and mean diffusivity are the first abnormalities to occur and that the first region to develop such significant differences was mesial parietal/splenial white matter; these metrics, however, remained relatively static with advancing disease indicating they are suitable as 'state-specific' markers. In contrast, increased radial diffusivity, and therefore decreased fractional anisotropy-though less detectable early-became increasingly abnormal with disease progression, and, in the splenium of the corpus callosum, correlated significantly with dementia severity; these metrics therefore appear 'stage-specific' and would be ideal for monitoring disease progression. In addition, the cross-sectional and longitudinal analyses showed that the progressive abnormalities in radial diffusivity and fractional anisotropy always occurred in areas that had first shown an increase in axial and mean diffusivity. Given that the former two metrics correlate with dementia severity, but the latter two did not, it would appear that increased axial diffusivity represents an upstream event that precedes neuronal loss.","Aged;Aged, 80 and over;Alzheimer Disease/diagnosis/pathology/radiography;Biomarkers;Cognition;Corpus Callosum/anatomy & histology/radiography;Dementia/pathology;Diffusion Magnetic Resonance Imaging/methods;Diffusion Tensor Imaging;Female;Humans;Male;Middle Aged","Acosta-Cabronero, J.;Alley, S.;Williams, G. B.;Pengas, G.;Nestor, P. J.",2012,,10.1371/journal.pone.0049072,0,
5724,"Cortical surface mapping using topology correction, partial flattening and 3D shape context-based non-rigid registration for use in quantifying atrophy in Alzheimer's disease","Magnetic resonance (MR) provides a non-invasive way to investigate changes in the brain resulting from aging or neurodegenerative disorders such as Alzheimer's disease (AD). Performing accurate analysis for population studies is challenging because of the interindividual anatomical variability. A large set of tools is found to perform studies of brain anatomy and population analysis (FreeSurfer, SPM, FSL). In this paper we present a newly developed surface-based processing pipeline (MILXCTE) that allows accurate vertex-wise statistical comparisons of brain modifications, such as cortical thickness (CTE). The brain is first segmented into the three main tissues: white matter, gray matter and cerebrospinal fluid, after CTE is computed, a topology corrected mesh is generated. Partial inflation and non-rigid registration of cortical surfaces to a common space using shape context are then performed. Each of the steps was firstly validated using MR images from the OASIS database. We then applied the pipeline to a sample of individuals randomly selected from the AIBL study on AD and compared with FreeSurfer. For a population of 50 individuals we found correlation of cortical thickness in all the regions of the brain (average r=0.62 left and r=0.64 right hemispheres). We finally computed changes in atrophy in 32 AD patients and 81 healthy elderly individuals. Significant differences were found in regions known to be affected in AD. We demonstrated the validity of the method for use in clinical studies which provides an alternative to well established techniques to compare different imaging biomarkers for the study of neurodegenerative diseases.","Adult;Aged;Algorithms;Alzheimer Disease/ pathology;Anatomy, Cross-Sectional;Atrophy;Biomarkers;Brain Mapping/ methods;Cerebral Cortex/ pathology;Female;Functional Laterality/physiology;Humans;Image Processing, Computer-Assisted/ methods;Imaging, Three-Dimensional;Magnetic Resonance Imaging/ methods;Middle Aged;Mild Cognitive Impairment/pathology;Neurodegenerative Diseases/pathology;Reproducibility of Results;Software","Acosta, O.;Fripp, J.;Dore, V.;Bourgeat, P.;Favreau, J. M.;Chetelat, G.;Rueda, A.;Villemagne, V. L.;Szoeke, C.;Ames, D.;Ellis, K. A.;Martins, R. N.;Masters, C. L.;Rowe, C. C.;Bonner, E.;Gris, F.;Xiao, D.;Raniga, P.;Barra, V.;Salvado, O.",2012,Mar 30,10.1016/j.jneumeth.2011.12.011,0,
5725,Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease,"Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia.","Aged;Aged, 80 and over;Alzheimer Disease/*metabolism/physiopathology;Aspartic Acid/*analogs & derivatives/metabolism;Brain Mapping;Case-Control Studies;Choline/metabolism;Cognition Disorders/etiology/*metabolism;Creatine/metabolism;Female;Hippocampus/*metabolism/physiopathology;Humans;Inositol/metabolism;Magnetic Resonance Imaging/methods;Magnetic Resonance Spectroscopy/methods;Male;Mental Recall/physiology;Middle Aged;Neuropsychological Tests/statistics & numerical data;Verbal Behavior/physiology","Ackl, N.;Ising, M.;Schreiber, Y. A.;Atiya, M.;Sonntag, A.;Auer, D. P.",2005,Aug 12-19,10.1016/j.neulet.2005.04.035,0,
5726,White matter signal abnormalities in children with suspected HIV-related neurologic disease on early combination antiretroviral therapy,"BACKGROUND: The natural history and manifestation of HIV-related neurologic disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging in children with HIV-related neurologic disease. METHODS: We reviewed magnetic resonance imaging scans of children with suspected HIV-related neurologic disease despite early ART and correlated with clinical, neurodevelopmental data, virologic markers and time on ART. These children were also on the Children with HIV Early Antiretroviral (CHER) trial. RESULTS: Magnetic resonance imaging scans were performed at a mean age 31.9 months (range 8-54) on 44 children: 10 on deferred and 34 on early treatment arms, commencing ART at mean age of 18.5 and 8 weeks, respectively. Multiple high signal intensity lesions on T2/fluid attenuated inversion recovery were documented in 22 patients (50%), predominantly in frontal (91%) and parietal (82%) white matter. No differences in neurodevelopmental scores comparing children with and without WMSA were found. Neither lesion load nor distribution showed significant correlation with neurodevelopmental scores or neurologic examination. Normal head growth was more common in the WMSA group (P = 0.01). There was a trend for association of WMSA and longer time on ART (P = 0.13) and nadir CD4% (P = 0.08). CONCLUSIONS: Half of children referred with HIV-related brain disease had WMSA on T2/fluid attenuated inversion recovery. Our findings of the association with normal head growth and duration of ART require further study. We suspect that WMSA can occur early and that initiating ART by 8 weeks of life may be too late to prevent HIV from entering the central nervous system.","AIDS Dementia Complex [drug therapy] [physiopathology];Anti-Retroviral Agents [therapeutic use];Antiretroviral Therapy, Highly Active;Brain [physiopathology];HIV Infections [drug therapy] [physiopathology];Leukoencephalopathies [physiopathology] [virology];Magnetic Resonance Imaging;Prospective Studies;South Africa;Child, Preschool[checkword];Female[checkword];Humans[checkword];Infant[checkword];Male[checkword]","Ackermann, C.;Andronikou, S.;Laughton, B.;Kidd, M.;Dobbels, E.;Innes, S.;Toorn, R.;Cotton, M.",2014,,10.1097/inf.0000000000000288,0,
5727,p(C) Analysis facilitates dementia diagnosis,"A modified receiver operating characteristic (ROC) analysis technique was applied to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical, imaging, neuropsychological, and laboratory evaluation guided experienced clinicians in clinical diagnosis, taken as the 'gold standard.' Two symptom inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's Type Inventory, were obtained by clinicians who were blind to final clinical diagnosis; scores on these inventories correlate with the likelihoods of multi-infarct dementia and Alzheimer's disease, respectively. A disjunctive sequential testing strategy was analyzed such that subthreshold scores on the first test identified patients for whom the second test was considered. Both tests were analyzed at all possible cutoff-point combinations and in both possible testing sequences. Diagnoses based on these tests were compared with the clinical 'gold standard' diagnoses to determine the accuracy of the testing procedures. The best strategy correctly classified 154/161 (95.6%) of the dementia patients and required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's Type Inventory) that were lower than those usually recommended for either test used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score-then Dementia of the Alzheimer's Type Inventory testing sequence was superior to the reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's disease, multi-infarct dementia, and other dementias) revealed similar test performances across a wide range of prevalences. These data suggest that simple clinical tests that take approximately 30 minutes to administer can produce diagnostic classifications of dementia that are similar to those of clinicians experienced in dementia diagnosis.",,"Absher, J. R.;Sultzer, D. L.;Mahler, M. E.;Fishman, J.",1994,1994,,0,
5728,New mutations in the Notch3 gene in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL),"BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebrovascular small-vessel disease caused by stereotyped mutations in the Notch3 gene altering the number of cysteine residues. METHODS: We directly sequenced exons 2-23 of the Notch3 gene in 30 unrelated Russian patients with clinical/neuroimaging picture suggestive of CADASIL. To confirm the pathogenicity of new nucleotide variants, we used the standard bioinformatics tools and screened 200 ethnically matched individuals as controls. RESULTS: We identified 16 different point mutations in the Notch3 gene in 18 unrelated patients, including 4 new missense mutations (C194G, V252M, C338F, and C484G). All but two mutations affected the cysteine residue. The non-cysteine change V322M was shown to be associated with CADASIL-specific deposits of granular osmiophilic material in the vascular smooth-muscle cells, which confirmed the pathogenicity of this Notch3 variant. Two patients were shown to be compound-heterozygotes carrying two pathogenic Notch3 mutations. The disease was characterized by marked clinical variability, without evident phenotype-genotype correlations. CONCLUSIONS: In our sample, 60% of Russian patients with 'clinically suspected' CADASIL received the definitive molecularly proven diagnosis. Careful assessment of genealogical, clinical, and neuroimaging data in patients with lacunar stroke can help selecting patients with a high probability of finding mutations on genetic screening.","Adult;Aged;Brain;CADASIL/*genetics/pathology;Exons;Female;Genetic Testing;Genotype;Humans;Magnetic Resonance Imaging;Male;Middle Aged;*Mutation;Mutation, Missense;Point Mutation;Polymerase Chain Reaction;Receptors, Notch/*genetics;Young Adult;Cadasil;Mutations;NOTCH3 gene;Phenotypic heterogeneity;Russian population;White matter lesions","Abramycheva, N.;Stepanova, M.;Kalashnikova, L.;Zakharova, M.;Maximova, M.;Tanashyan, M.;Lagoda, O.;Fedotova, E.;Klyushnikov, S.;Konovalov, R.;Sakharova, A.;Illarioshkin, S.",2015,Feb 15,10.1016/j.jns.2015.01.018,0,
5729,Frontotemporal white matter changes in amyotrophic lateral sclerosis,"Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n=11; ALSu, cognitively unimpaired n=12) were compared with healthy age matched controls (n=12). A comparison of the ALSi group with controls revealed significantly (p<0.002) reduced white matter volume in extensive motor and non-motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non-demented ALS patients. The results also suggest that extra-motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra-motor cerebral and cognitive change in this disorder.","Adult;Amyotrophic Lateral Sclerosis/classification/complications/metabolism/ pathology;Analysis of Variance;Brain Mapping;Case-Control Studies;Female;Frontal Lobe/metabolism/ pathology;Humans;Intelligence/physiology;Magnetic Resonance Imaging/methods;Male;Memory/physiology;Middle Aged;Neuropsychological Tests/statistics & numerical data;Positron-Emission Tomography/methods;Problem Solving/physiology;Speech Disorders/etiology/metabolism/pathology;Statistics as Topic;Temporal Lobe/metabolism/ pathology;Vision, Ocular/physiology","Abrahams, S.;Goldstein, L. H.;Suckling, J.;Ng, V.;Simmons, A.;Chitnis, X.;Atkins, L.;Williams, S. C.;Leigh, P. N.",2005,Mar,10.1007/s00415-005-0646-x,0,
5730,Phenotypic comparison of individuals with homozygous or heterozygous mutation of NOTCH3 in a large CADASIL family,"Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in NOTCH3, very rarely homoallelic. Objective To describe the clinical, radiological, and neuropsychological features in an extended CADASIL family including members with either a homozygous or heterozygous NOTCH3 R1231C mutation. Methods The pedigree included 3 generations of a family with 13 affected individuals. The patients were examined clinically and radiologically. Neuropsychological testing was performed on the proband. Sequencing of the entire coding DNA sequence (CDS) and flanking regions of NOTCH3 was undertaken using PCR amplification and direct Sanger sequencing. Results Homozygous C3769T mutation, predicting R1231C in exon 22 of NOTCH3 was found in 7 family members. Six other family members harbored the same in the heterozygous state. Homozygous individuals showed a slightly more severe clinical and radiological phenotype of earlier onset compared to their heterozygous counterparts. Conclusion This study reports the largest number of patients with homozygous NOTCH3 mutation. The phenotype and imaging features of homozygous individuals is within the spectrum of CADASIL, although slightly at the severe end when compared to heterozygotes carrying the same mutation. Both genetic modifiers and environmental factors may play an essential role in modification and alteration of the clinical phenotype and white matter changes among CADASIL patients.",Notch3 receptor;adolescent;adult;aged;amino acid substitution;article;asymptomatic disease;CADASIL;cerebrovascular accident;child;clinical article;clinical feature;consanguinity;dementia;disease severity;DNA flanking region;exon;family;female;gene amplification;gene mutation;gene sequence;genetic analysis;heterozygote;homozygote;human;male;middle aged;migraine with aura;migraine without aura;mutational analysis;neuropsychological test;night blindness;nuclear magnetic resonance imaging;pedigree;phenotype;polymerase chain reaction;priority journal;Sanger sequencing;school child;seizure;young adult,"Abou Al-Shaar, H.;Qadi, N.;Al-Hamed, M. H.;Meyer, B. F.;Bohlega, S.",2016,,,0,
5731,Asymptomatic encephalic calcifications in postsurgical hypoparathyroidism,"Introduction. Encephalic calcifications (EC) are a frequent finding in neuroimaging of CT scans, which have many causes, both symptomatic and asymptomatic. This paper has aimed to report a series of patients who had had a previous thyroidectomy years earlier in whom the presence of hypoparthyroidism (HP) EC and their clinical manifestations had been analyzed. Patients and methods. A group of 38 women who had undergone a thyroidectomy from 14 to 45 years ago were evaluated. The EC was mild in 2 cases, located exclusively in the pale globe and putamen. It was moderate in two other patients, the calcinosis spreading towards the caudate nucleus, and one patient was considered severe or very extended, affecting the basal ganglia, cerebellum and white matter of semioval centers. Results. Six patients (15%) had HP; five of them (13%) with EC. The neurological examination and the UPDRS scale were normal, including negative Chvostek and Trousseau signs. Cognition was evaluated with: Mini-Mental State Examination, Clock Drawing test, Alzheimer's Disease Assessment Scale-cognitive, Trail Making Test Part A and B and the Clinical Dementia Rating, of which were normal. In these six patients, serum calcium (Ca) and paratohormone (PTH) levels were reduced and phosphorus values increased. Conclusions. It is likely that the EC are sub-diagnosed in postsurgical HP due to the absence of symptoms. There is still an ongoing debate on the appearance of symptoms and extension of EC, possibly when the Ca and PTH variables only have a moderate reduction, corresponding to a variable that avoids manifestations.",calcium;parathyroid hormone;adult;aged;article;basal ganglion;brain calcification;calcium blood level;caudate nucleus;cerebellum;clinical article;cognition;controlled study;disease severity;female;hormone blood level;human;hypoparathyroidism;Mini Mental State Examination;neurologic examination;putamen;thyroidectomy;Unified Parkinson Disease Rating Scale;white matter,"Abiusi, G.;Domínguez, R. O.;Parada Marcilla, M.;Lesyk, S.;Laguarde, N.;Yobstraibizer, F.",2009,,,0,
5732,Hypertensive Disorders of Pregnancy Appear Not to Be Associated with Alzheimer's Disease Later in Life,"BACKGROUND: After hypertensive disorders of pregnancy, more subjective cognitive complaints and white matter lesions are reported compared to women after normal pregnancies. Both have a causal relationship with Alzheimer's disease (AD). AIM: To investigate if women whose pregnancy was complicated by hypertensive disorders have an increased risk of AD. METHODS: A case-control study in women with AD from the Alzheimer Center of the VU University Medical Center Amsterdam and women without AD. Paper and telephone surveys were performed. RESULTS: The response rate was 85.2%. No relation between women with (n = 104) and without AD (n = 129) reporting pregnancies complicated by hypertensive disorders (p = 0.11) was found. Women with early-onset AD reported hypertensive disorders of pregnancy more often (p = 0.02) compared to women with late-onset AD. CONCLUSION: A reported history of hypertensive disorders of pregnancy appears not to be associated with AD later in life.",,"Abheiden, C. N.;van Doornik, R.;Aukes, A. M.;van der Flier, W. M.;Scheltens, P.;de Groot, C. J.",2015,Sep-Dec,10.1159/000439043,0,
5733,Atypical juvenile neuronal ceroid liposfuscinosis with granular osmiophilic deposit-like inclusions in the autonomic nerve cells of the gut wall,"In this 8-year-old boy, who had been exposed to alcohol and oxazepam during pregnancy, visual failure was the first symptom of a neuronal ceroid lipofuscinosis (NCL) disorder, noticed at the age of 5 years. Ophthalmological examinations revealed a cystic type of macular degeneration, which would be more likely to be found in variant late infantile NCL. However, vacuolated lymphocytes were found in peripheral blood films and a diagnosis of the juvenile form of NCL (JNCL) was made. Molecular genetic studies showed the patient to be homozygous for the major mutation of JNCL, a 1.02-kb deletion. In whole-night polysomnography, there was significantly more epileptiform activity than in other JNCL patients under 10 years of age. Using magnetic resonance imaging, the signal intensity of the white matter was increased, especially in the periventricular area. In addition, there were enlarged perivascular spaces in the watershead areas. The corpus callosum was thin. Finally, in the autonomic ganglion cells of the submucosal nerve plexus there were membrane-enclosed homogeneous and granular cytosomes resembling the granular osmiophilic deposits of infantile NCL. However, extraneural cells, including blood capillaries and smooth muscle, showed inclusions with fingerprint and curvilinear profiles. The features of the present case indicated a phenotypic variant of JNCL.",,"Aberg, L.;Järvelä, I.;Rapola, J.;Autti, T.;Kirveskari, E.;Lappi, M.;Sipilä, L.;Santayuori, P.",1998,1998,,0,
5734,Multiple Dural Arteriovenous fistulas causing rapid progressive dementia successfully treated by endovascular surgery: Case report,"A 67-year-old female presented with multiple dural arteriovenous fistulas (AVFs) manifesting as dementia rapidly progressing over 2 months. The initial diagnosis was Creutzfeldt-Jakob disease based on the acute clinical course. However, angiography eventually revealed multiple dural AVFs involving the bilateral convexities to the superior sagittal sinus and the right transverse-sigmoid sinus. Endovascular treatment combining arterial and venous embolization in multiple stages proved to be effective, as the hemodynamic pathology improved, and the patient recovered from dementia. The cause of the dementia was thought to be venous hypertension in the deep white matter induced by the dural AVFs. Dural AVFs should be included in the differential diagnosis of rapidly progressive dementia.",enbucrilate;aged;angiography;arteriovenous fistula;arteriovenous shunt;article;brain angiography;brain blood flow;case report;Creutzfeldt Jakob disease;dementia;differential diagnosis;endovascular surgery;female;Glasgow coma scale;headache;human;hypertension;leukoaraiosis;Mini Mental State Examination;nausea;nuclear magnetic resonance imaging;quadriplegia;sigmoid sinus;single photon emission computer tomography;superficial temporal artery;superior sagittal sinus,"Abe, K.;Okuda, O.;Ohishi, H.;Sonobe, M.;Arai, H.",2014,,,0,
5735,Clinical Features of CADASIL,"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks, strokes, and vascular dementia. Various mutations in the Notch3 gene cause the disease, whereas the mechanism of how they cause the disorder remains unknown. We recently identified two Japanese CADASIL families with an R141C mutation. The mean age of onset was 44.6, and the main symptoms were recurrent strokes and progressive motor disturbances in extremities, as well as pseudobulbar palsy. Besides those in white matter and basal ganglia, ischemic lesions in temporal edge and corpus callosum were present on magnetic resonance images, which seemed to be characteristic of CADASIL. Moreover, in our cases, nocturnal arterial blood pressure fall was significantly lower in patients compared with control subjects, suggesting that it might be partly associated with ischemic lesions in deep white matter in CADASIL. We also compared Japanese and Caucasian CADASIL cases and found that dementia and pseudobulbar palsy were observed more frequently in Japanese patients, although typical migraine was rather rare. In the present study, we describe the clinical features of CADASIL, hoping to help reveal the mechanism of chronic ischemic brain diseases, including leukoaraiosis or Binswanger's disease.","Adult;Age of Onset;Blood Pressure;Brain/ pathology;Circadian Rhythm;Dementia, Multi-Infarct/ genetics/ pathology/physiopathology;Female;Humans;Magnetic Resonance Imaging;Male;Middle Aged;Pedigree","Abe, K.;Murakami, T.;Matsubara, E.;Manabe, Y.;Nagano, I.;Shoji, M.",2002,Nov,,0,
5736,Embolic Protection Devices During TAVI: Current Evidence and Uncertainties,"Transcatheter aortic valve implantation (TAVI) is now the principal therapeutic option in patients with severe aortic stenosis deemed inoperable or at high surgical risk. Implementing TAVI in a lower risk profile population could be limited by relatively high cerebrovascular event rates related to the procedure. Diffusion-weighted magnetic resonance imaging studies have demonstrated the ubiquitous presence of silent embolic cerebral infarcts after TAVI, with some data relating these lesions to subsequent cognitive decline. Embolic protection devices provide a mechanical barrier against debris embolizing to the brain during TAVI. We review the current evidence and ongoing uncertainties faced with the 3 currently available devices (Embrella, TriGuard and Claret) in TAVI. Studies evaluated neurological damage at 3 levels: clinical, subclinical, and cognitive. Feasibility and safety were analyzed for the 3 devices. In terms of efficacy, all studies were exploratory, but none demonstrated significant reductions in clinical event rates. The Embrella and Claret devices demonstrated significant reductions of the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging. Studies evaluating the effects on cognition were also somewhat inconclusive. In conclusion, despite embolic protection devices demonstrating reductions in the total cerebral lesion volume on diffusion-weighted magnetic resonance imaging, the clinical efficacy in terms of preventing stroke/cognitive decline requires confirmation in larger studies. Full English text available from: www.revespcardiol.org/en",embolic protection device;brain damage;cerebrovascular accident;cognition;device safety;diffusion weighted imaging;exploratory research;feasibility study;human;mental deterioration;neuroimaging;neurologic disease;short survey;transcatheter aortic valve implantation;tumor volume;uncertainty;Claret;Embrella;TriGuard,"Abdul-Jawad Altisent, O.;Puri, R.;Rodés-Cabau, J.",2016,,10.1016/j.recesp.2016.04.047,0,
5737,Somatosensory evoked potentials in lacunar syndromes,"Parietal and prerolandic somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded from 40 patients with lacunar syndromes due to CT-verified lacunar infarcts. The control group consisted of 30 age-matched normal controls. Nineteen patients showed SEP abnormalities, mainly an increase of height-covariated latency of cortical components and/or of the central conduction time. Such changes occurred independently of the clinical features of lacunar syndromes, being related more to the lesion location than to its size. SEP studies may be a useful adjunct to the clinical diagnosis of lacunar infarct, possibly also when the CT scans are normal.",adult;brain cortex;brain infarction;clinical article;computer analysis;evoked somatosensory response;female;human;male;multiinfarct dementia;priority journal,"Abbruzzese, G.;Bino, G.;Dall'Agata, D.;Morena, M.;Primavera, A.;Favale, E.",1988,,,0,
5738,Thalamic dementia: report of a case with unusual lesion location,"Thalamic dementia usually results from a bilateral paramedian thalamic infarction. We report a case with typical clinical and neuropsychological features of thalamic dementia, but with CT evidence of an unusual and asymmetrical location of ischemic lesions. Somatosensory evoked potential recordings were consistent with a left medial thalamic infarction, associated with a contralateral lesion, possibly at lemniscal level. This case suggests that thalamic dementia may develop following a unilateral paramedian thalamic infarction.",adult;article;brain disease;brain ischemia;case report;computer assisted tomography;dementia;evoked somatosensory response;human;male;median nerve;nerve conduction;neuropsychological test;neuropsychology;pathophysiology;psychological aspect;radiography;reaction time,"Abbruzzese, G.;Arata, L.;Bino, G.;Dall'Agata, D.;Leonardi, A.",1986,,,0,
5739,Clinical and neuroimaging profile of HIV-1 encephalopathy in infancy and childhood in a sub-Saharan African country,"BACKGROUND: Neurological dysfunction in AIDS is common, occurring in as many as eighty percent of children. Thus, it is important to recognize the central nervous system imaging appearance of HIV, in particular those of HIV encephalopathy, as this is an AIDS defining illness and with distinct neuro-imaging features essential for early diagnosis and timely therapeutic intervention AIM: To identify the clinical features in HIV-1 infection of the central nervous system and their associated neuroradiological correlates. METHODS: Retrospective review of the records of all children with HIV-1 encephalopathy identified among children with neurological and developmental problems and who were on follow up at a child development and neurology clinic in an African city. RESULTS: A total of 22 children (10 male and 12 female) with HIV-1 encephalopathy were identified among 2382 children with various forms of neurological and developmental problems and who were on follow up at a child development and neurology clinic for a little bit over eight years period. All the children acquired the infection vertically. The age range of these children was between 10 months to 14 years. The median age was 5.6 years. The mean duration of symptom was 3.2 years. Global delay or regression in development along with signs of pyramidal tract involvement and seizures were the commonest clinical signs observed in these children. Neuro-behavioral problems were commonly observed among preschool and school aged children. In older children and preadolescents focal seizures with or with out neurologic deficit and neuroradiological findings were common. Nonhemorrhagic stroke was rare and occurred in one child and another child had cortical blindness. Three children had no neurological deficit. Rapid progression of the disease carried grave prognosis. Opportunistic infections and tumors of the central nervous system were also uncommon among these children. Brain volume loss with dilatation of the lateral ventricle, bilateral symmetrical or asymmetrical calcification of the basal ganglia and periventricular involvement of the white matter were the commonest neuro-radiological findings observed in these children. CONCLUSION: Atrophy of the brain with dilatation of the lateral ventricles and calcification of the basal ganglia and peri-ventricular involvement of the white matter were the commonest neuro-radiological findings in children with HIV-1 encephalopathy. Similarly global delay or regression in development along with pyramidal tract signs and seizures were the commonest neurological findings. Behavioral problems were common in preschool and school aged children. Focal seizures were common in older children and preadolescents. Rapid progression of the disease carried grave prognosis.","AIDS Dementia Complex/complications/ radiography/virology;Adolescent;Atrophy/radiography/virology;Basal Ganglia Diseases/ radiography/virology;Brain/ pathology/ radiography;Calcinosis/ radiography/virology;Child;Child, Preschool;Developmental Disabilities/virology;Dilatation, Pathologic/radiography/virology;Ethiopia;Female;Hiv-1;Humans;Infant;Lateral Ventricles/radiography/virology;Male;Seizures/virology","A, G. M.;Assefa, G.",2012,Oct,,0,
5740,White matter hyperintensities volume associated with Alzheimer's disease,,amyloid beta protein;Alzheimer disease;brain blood flow;cerebrovascular disease;cognitive defect;diabetes mellitus;disease association;human;hypertension;note;nuclear magnetic resonance imaging;obesity;pathogenesis;predictive value;priority journal;risk factor;white matter lesion,,2013,,,0,
5741,"Singapore Health and Biomedical Congress, SHBC 2013","The proceedings contain 327 papers. The special focus in this conference is on Health and Biomedicine. The topics include: Reducing the rate of postoperative endophthalmitis over 11 years-results of a new intervention using intracameral antibiotics; corpus callosum morphology in first episode and chronic schizophrenia; differences in late cardiovascular mortality following acute myocardial infarction among three major Asian ethnicities; exploring relationship of retinal thickness on optical coherence tomography and visual acuity in patients with diabetic macular edema; medication reconciliation in outpatient hospital clinics; utilising discharge planning tools in an inpatient psychiatric rehabilitation services to promote positive clinical outcomes; seven-point subjective global assessment is more time sensitive than conventional subjective global assessment in detecting nutritional changes; Singapore hospice nurses perspectives about spirituality and spiritual care; enhanced infarct stabilisation and cardiac repair with an injectable PEGylated-fibrinogen hydrogel carrying vascular endothelial growth factor (VEGF); identification of tumour suppressive MicroRNAs in multiple myeloma by pharmacologic unmasking; use of a novel stereographic projection software to calculate precise area of peripheral non-perfusion and its correlation with manual grading; a protocol to reduce inter-reviewer variability in computed tomography measurement of orbital floor fractures; impact of genome wide supported psychosis susceptibility NRGN gene on thalamocortical morphology in schizophrenia; improved outcome of myeloma patients in a tertiary hospital; femoral neck fractures-factors affecting ambulatory status in elderly patients more than 65 years old who underwent hip hemiarthroplsty; exploratory factor analysis of the Zarit burden interview in a multi-ethnic Asian community sample; prevalence, awareness, treatment and control of hypertension among Singapore elderly residential population; predictive factors of unscheduled 15-day hospital readmissions; lost in transition-newly qualified registered nurses and their transition to practice journey; national healthcare group clinical educators reflection on web2.0's application in enhancing teaching and lifelong learning in medical education; determinants of clarification studies in medical education research; hypoglycemia management of patients with type 2 diabetes in primary care setting; photograph-assisted dietary review amongst type 2 diabetics in primary care; exploring the feasibility of advanced care planning in persons with early cognitive impairment; roles of miR-186 in circulating tumour cells (CTCs)-mediated metastasis in breast cancer; characterisation of the biological and clinical relevance of RUNX genes in natural killer T-cell lymphoma; a randomised controlled trial comparing single-injection and continuous femoral nerve blocks with patient-controlled analgesia; magnetic resonance imaging (MRI) changes in lower limbs in transition to frailty; prevalence of dilutional hyponatraemia in inpatients and outpatients in Singapore; a prospective randomised study on the patency period of the plastic anti-reflux biliary stent; an academic-practice collaboration through simulation learning; a multicentre study of physiotherapists' knowledge and perceptions in palliative care; post discharge pain experiences following total knee arthroplasty; characteristics of subjective QOL of elderly people with dementia in china and Japan; audit of readmissions to a palliative care unit in a tertiary hospital; factors affecting psychological distress in informal caregivers of Singapore elderly; prevalence of anaemia in patients on aspirin medication in a primary care setting; patient satisfaction with pharmacist-managed hypertension-diabetes-lipids clinic and its relation to medication adherence and beliefs about medication; anthropometric measures and cognition in the Singapore elderly; clinical decision support for high-priority drug-drug interactions; a normative study on the national university health system aphasia screening test; a pilot study on the integration of a cognitive-behavioral therapy-based computer game in the clinical treatment of childhood anxiety; barriers of whole-grain intake among healthcare workers in national healthcare group polyclinics; a novel approach to lead screening; effects of computed tomography contrast on bone scans; prevalence and predictors of employment among the Singaporean elderly; evaluating the impact of inpatient accelerated palliative radiation therapy programme in reducing inpatient hospitalisation; socio-demographic correlates of positive mental health; unravelling the relationship between obesity, schizophrenia and cognition; relationship between measures of mental health and functional impairment in primary care; body mass index of elderly persons in Singapore; improving the influenza and pneumococcal vaccination rate of eligible patients with chronic heart failure; reducing near misses from packing errors in inpatient pharmacy; pharmacy-led smoking cessation clinic in dermatology; investigation of high platelet count in random platelet unit and its viability; public attitudes towards mentally-ill persons in Singapore; revisiting the association between parental bonding and risk for psychopathology; pharmacist reviews and outcomes in nursing homes in Singapore; evaluation of the inpatient smoking cessation programme in tan Tock Seng hospital; community forums are effective in improving osteoporosis knowledge; profile of patients referred for podiatry services in primary care; novel use of tigecycline for multiple myeloma in vitro-alternative non-mitochondrial pathways; linking human leucine-rich repeat kinase 2 (LRRK2) gene mutation to cancer development; haploinsufficiency of TP53 in multiple myeloma; bioactive and conductive collagen scaffold for wound healing augmented by electrical stimulation; systematic discovery of novel cilia and ciliopathy genes through functional genomics in the zebrafish; extracellular matrix-based biohybrid skin substitutes; enzyme sensor system for determination of total cholesterol in human serum; intestinal microbial study of gout patients; differences in gut microbiome between schizophrenic patients and healthy individuals; changes in gait associated with sarcopenia; noncultured cellular grafting for vitiligo-a three-year follow-up study; bariatric surgery and its impact on sleep; clinico-epidemiological profile of moderate to severe paediatric atopic dermatitis; influenza vaccination of healthcare workers; a snapshot of audits in the phototherapy unit; a naturalistic longitudinal study in healthy children; retrospective study on autoimmune blistering disease in paediatric patients; association between CHA65S2 score and obstructive sleep apnoea; primary localised cutaneous amyloidosis; high STOP-BANG scores herald adverse perioperative outcomes; neurobehavioral outcomes after traumatic brain injury; extended outcomes by dialysis modality selection in incident patients with end-stage renal disease and ischaemic cardiomyopathy; laparoscopic gastrectomies in gastric cancer patients; survey on factors influencing medication adherence in psychiatric patients; serum brain-derived neurotrophic factor and metabolic indices in patients with schizophrenia; outcomes of non-Tbitrauma patients in a surgical intensive care unit; evaluation of patients screened for MERS-CoV infection at tan Tock Seng hospital, Singapore; thinking twice before using the LMA for obese and older patients-a prospective observational study; comparison study between two apheresis machines; diabetes knowledge in older adults with type 2 diabetes in Singapore; establishing an intensive care unit database; necrotising fasciitis of the head and neck; diabetic chronic kidney disease patients should increase protein intake; the skin-endocrine axis in the management of dermatology patients; dematiaceous mycoses of the skin in Singapore from 2003 to 2010; profile of hearing aids users in Singapore; factors that affect the degree of hearing loss at presentation and hearing aid us ge; cross diagnostic comparisons of quality of life between schizophrenia and bipolar disorder patients; value of hearing questionnaire in predicting hearing impairment; utility of self-perception of hearing loss questions in predicting hearing impairment; burnout, challenges and supportive factors in hospital doctors; exploring stereotypes in healthcare professions; health sciences virtual hospital game as a learning tool in nursing education; application of the RIME framework for education administrators' competencies; bed exit alarm as a novel tool for fall prevention; when prolonged preoperative fasting is a myth; time-motion study for nursing aides activities in a psychiatric hospital; impact of an advanced practice nurse-led heart failure clinic in a secondary hospital in Singapore; managing individuals with diabetes using the diabetes ambulatory stabilisation services (DASS); streamlining process flow for maintenance of 12-lead ECG machine in a cardiology ward; factors of rehabilitation outcomes in primary care physiotherapy; dietary intake of wholegrains of healthcare workers in national healthcare group polyclinics; management of patients with diabetes in two primary care podiatry clinics; preliminary evaluation of shoulder conditions in primary care physiotherapy; prevalence of alcohol problems among elderly in Singapore; prevalence and predictors of tobacco use in elderly Singaporeans; mortality predictors for operative hip fracture patients; a risk index to predict 30 days emergency hospital readmission; compliance of preoperative chest X-rays in anaesthesia clinic; predictors of mortality in patients with chronic kidney disease; continuity of care issues in the Singapore health system; factors influencing patients adherence to follow-up post bariatric surgery; a snapshot of audits in the phototherapy unit; health screening perceptions in Singapore-a grounded theory study; interactive dashboard for monitoring operating theatre operational efficiency; reducing violence through the use of structured therapies; early home visits by care coordinators help to reduce hospital readmission rate; evaluation of a workplace nutrition programme at a hospital; a review of the use of electroencephalography in autism spectrum disorder in the past decade; an alternate plastic packaging to reduce threat of e coli contamination; spatial epidemiology of tuberculosis in Singapore; development of a polarised cellular model for Chikungunya virus infection; summer-winter differences in total vitamin D concentrations in Singapore; effect of femoral nerve block on ambulation following total knee arthroplasty; development of a computer-based objective grading system for facial paralysis; a preliminary finding of EEG differences of children with disruptive behaviour disorders in Singapore; sex hormone concentrations in Singaporean men; deciding where to allocate diabetic educational resources; pseudoexfoliation syndrome at a Singapore eye clinic; corneal thickness in Asian keratoconus patients; reasons influencing non-adherence to medications in psychiatric patients; pilot study on nurses' perceptions towards different aspects of learning; oral conditions among dependent community-dwelling elderly persons; knowledge of osteoporosis among Singapore adults in national healthcare group polyclinics (NHGP) settings and knowledge adequacy of diagnosis and treatment plans of elderly patients on discharge from tertiary hospital.",health;Singapore;human;patient;hospital;aged;diabetes mellitus;primary medical care;health care;prevalence;schizophrenia;hospital patient;hospital readmission;hearing impairment;multiple myeloma;health care personnel;drug therapy;medical audit;Asian;gene;skin;mental patient;learning;tertiary health care;outpatient department;podiatry;medical education;mortality;osteoporosis;medication compliance;computer;outpatient;total knee replacement;femoral nerve;nerve block;follow up;serum;diagnosis;pilot study;hypertension;community;machine;pharmacist;hearing aid;smoking cessation;dermatology;heart failure;physiotherapy;adult;intensive care unit;morphology;bariatric surgery;phototherapy;palliative therapy;chronic kidney disease;nurse;pharmacy;computer assisted tomography;neoplasm;cognition;risk;non insulin dependent diabetes mellitus;mental health;child;computer program;diabetic macular edema;obesity;acute heart infarction;influenza;biomedicine;vaccination;lifelong learning;hypoglycemia;radiotherapy;day hospital;screening;nutrition;population;anxiety;monitoring;childhood;mass screening;anesthesia;cognitive therapy;screening test;aphasia;community sample;interview;decision support system;factorial analysis;cardiovascular mortality;hydrogel;hip;male;patient satisfaction;femur neck fracture;infarction;visual acuity;registered nurse;protein intake;Japan;China;quality of life;distress syndrome;caregiver;anemia;hospital physician;education;diet restriction;nursing assistant;mental hospital;advanced practice nurse;ward;rehabilitation;dietary intake;shoulder;drug interaction;university;hip fracture;thorax radiography;patient care;grounded theory;operating room;violence;grain;electroencephalography;autism;contamination;bone scintiscanning;employment;mobilization;facial nerve paralysis;disruptive behavior;functional disease;body mass;teaching;intracameral drug administration;dementia;spiritual care;apheresis;infection;pain;religion;optical coherence tomography;stomach cancer;physiotherapist;ischemic cardiomyopathy;multicenter study;kidney failure;simulation;biliary stent;traumatic brain injury;retinal thickness;amyloidosis;hyponatremia;hospice;leg;nuclear magnetic resonance imaging;influenza vaccination;rehabilitation center;ethnicity;endophthalmitis;sleep;patient controlled analgesia;myeloma;vitiligo;sarcopenia;gait;microbiome;hospital discharge;intestine;gout;injection;psychosis;randomized controlled trial;atopic dermatitis;longitudinal study;genome;retrospective study;sleep disordered breathing;cholesterol blood level;enzymic biosensor;dialysis;NK T cell lymphoma;fracture;gastrectomy;extracellular matrix;cancer patient;zebra fish;functional genomics;observational study;data base;fasciitis;neck;eukaryotic flagellum;mycosis;electrostimulation;wound healing;breast cancer;bipolar disorder;hearing;questionnaire;self concept;burnout;stereotypy;occupation;health science;nursing education;administrative personnel;prevention;literature;metastasis;cardiology;orbit;haploinsufficiency;circulating tumor cell;gene mutation;tobacco;cognitive defect;in vitro study;planning;medication therapy management;nursing home;mental disease;photography;thrombocyte;therapy;professional practice;workplace;book;thrombocyte count;packaging;Escherichia coli;epidemiology;tuberculosis;model;chikungunya;summer;winter;perfusion;corpus callosum;diseases;pseudoexfoliation;eye;cornea thickness;keratoconus;electroencephalogram;electrocardiogram;plastic;antibiotic agent;vitamin D;microRNA;vasculotropin;fibrinogen;acetylsalicylic acid;lipid;alcohol;sex hormone;brain derived neurotrophic factor;collagen;leucine rich repeat kinase 2;tigecycline,,2013,,,0,
5742,Silent brain infarcts may cause dementia,,Alzheimer disease;blood analysis;brain blood vessel;brain infarction;cardiovascular risk;cause of death;cognitive defect;dementia;disease association;follow up;human;neuropsychological test;note;nuclear magnetic resonance imaging;population research;risk factor;vascular disease,,2003,,,0,
5743,Presence of silent brain infarcts may have prognostic value,,aged;brain infarction;cognition;dementia;disease association;follow up;high risk population;human;memory;neuropsychological test;note;nuclear magnetic resonance imaging;prognosis;psychomotor performance;risk assessment;scoring system,,2003,,,0,
5744,CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy),,adult;article;brain;case report;cerebral artery disease;cerebrovascular disease;computer assisted tomography;genetics;human;male;multiinfarct dementia;nuclear magnetic resonance imaging;pathology;radiography,,1997,,,0,
5745,European Pentoxifylline Multi-Infarct Dementia Study,"A double-blind, placebo-controlled, parallel-group, multicentre study was conducted to evaluate the efficacy of pentoxifylline (Trental) in patients with multi-infarct dementia (MID) according to DSM-III-R criteria. Men and women aged 45 years or older, with a Hachinski Ischemia Scale score > or = 7 and a Mini Mental State Examination (MMSE) score of 10-25 at entry, and computed tomographic evidence of vascular disease were enrolled. A total of 289 patients were randomised to receive either oral pentoxifylline 400 mg t.i.d. or placebo for 9 months, and efficacy was assessed every 3 months. The primary outcome variable was the difference in scores between the two treatment groups, as measured on the Gottfries, Bråne, Steen (GBS) scale. Secondary outcome variables included the scores achieved on the Sandoz Clinical Assessment Geriatric (SCAG) scale and MMSE, and a battery of psychological and other tests. The intention-to-treat analysis for patients completing the study (n = 239) showed a statistically significant difference in the total GBS score in favour of pentoxifylline (improvement of 3.5 points, p = 0.028). A significant difference in the total GBS score in favour of pentoxifylline was even almost achieved in the intention-to-treat analysis for all evaluable patients (n = 269, improvement of 2.1 points, p = 0.065). It is concluded that treatment with pentoxifylline is beneficial for patients with MID, the global results of the GBS and SCAG scales being reinforced by significant improvements in those subscales specific for intellectual and cognitive function.","Aspirin [therapeutic use];Dementia, Multi-Infarct [drug therapy] [psychology] [radiography];Double-Blind Method;Drug Therapy, Combination;Pentoxifylline [adverse effects] [therapeutic use];Psychiatric Status Rating Scales;Tomography, X-Ray Computed;Treatment Outcome;Aged[checkword];Aged, 80 and over[checkword];Female[checkword];Humans[checkword];Male[checkword];Middle Aged[checkword];Sr-dementia",,1996,,,0,
5746,White matter lesions on MRI in the elderly: What do they mean?,,aging;dementia;human;methodology;note;nuclear magnetic resonance;priority journal;white matter,,1990,,,0,